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Seki K, Munkhdelger J, Bychkov A, Tanaka T, Kunugi S, Saito-Koyama R, Kashima Y, Zaizen Y, Okudela K, Kataoka K, Yamano Y, Kondoh Y, Johkoh T, Fukuoka J. Challenges in recognizing airway-centered fibrosis: Observer concordance and its role in fibrotic hypersensitivity pneumonitis. Respir Investig 2025; 63:314-321. [PMID: 40054038 DOI: 10.1016/j.resinv.2025.02.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2024] [Revised: 02/01/2025] [Accepted: 02/05/2025] [Indexed: 04/23/2025]
Abstract
BACKGROUND The interobserver agreement regarding airway-centered fibrosis (ACF), the key diagnostic feature of fibrotic hypersensitivity pneumonitis (fHP) has not been sufficiently addressed to date. We applied digital image analysis to investigate this issue and extracted histological features of ACF to correlate with fHP diagnosis. METHODS A total of 111 selected glass slides from 17 fHP and 30 idiopathic pulmonary fibrosis (IPF) were scanned and seven expert pulmonary pathologists were tasked with digital annotation of ACF. Interobserver agreement on annotated ACF was assessed using Fleiss' kappa value. ACF recognized by majority of pathologists (4 or more) were considered as consensus ACF (cACF), and their frequencies were compared between fHP and IPF cases. RESULTS Fleiss' kappa agreement in ACF recognition was 0.32 among seven pathologists. A significant difference between cryobiopsy and VATS specimens regarding an average ACF count per slide (p = 0.012) was found. The number of cACFs in a single case ranged from 0 to 20 (mean 5.71) for fHP cases and 0 to 13 (mean 1.80) for IPF cases (p = 0.011). When limited to surgical biopsies, the average number of cACF was 10.3 for fHP vs. 1.68 for IPF (p < 0.001). The common characteristic features of cACF in fHP were their confinement to the vicinity of respiratory bronchioles, frequent association with peribronchiolar metaplasia, and mild to moderate lymphocytic infiltration. CONCLUSIONS The recognition of ACF varies widely among pathologists. We identified common histologic features of ACF in fHP cases, proposing criteria for ACF recognition in fHP.
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Affiliation(s)
- Kurumi Seki
- Department of Pathology Informatics, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1, Sakamoto, Nagasaki, 852-8523, Japan; Department of Pathology, Kameda Medical Center, 929, Higashi-cho, Kamogawa City, Chiba, 296-0041, Japan
| | - Jijgee Munkhdelger
- Department of Pathology, Kameda Medical Center, 929, Higashi-cho, Kamogawa City, Chiba, 296-0041, Japan
| | - Andrey Bychkov
- Department of Pathology Informatics, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1, Sakamoto, Nagasaki, 852-8523, Japan; Department of Pathology, Kameda Medical Center, 929, Higashi-cho, Kamogawa City, Chiba, 296-0041, Japan
| | - Tomonori Tanaka
- Department of Diagnostic Pathology, Kobe University Hospital, 7-5-2, Kusunoki-cho, Kobe City, Hyogo, 650-0017, Japan
| | - Shinobu Kunugi
- Department of Analytic Human Pathology, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan
| | - Ryoko Saito-Koyama
- Department of Pathology, National Hospital Organization, Sendai Medical Center, 2-11-12, Miyagino, Miyagino-ku, Sendai City, Miyagi, 983-8520, Japan
| | - Yukio Kashima
- Department of Pathology, Awaji Medical Center, 1-1-137, Shioya, Sumoto City, Hyogo, 656-0021, Japan
| | - Yoshiaki Zaizen
- Department of Pathology Informatics, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1, Sakamoto, Nagasaki, 852-8523, Japan; Division of Respirology, Neurology, and Rheumatology, Department of Medicine, Kurume University School of Medicine, 67, Asahi-machi, Kurume City, Fukuoka, 830-0011, Japan
| | - Koji Okudela
- Department of Pathology, Saitama Medical University, 38, Morohongo, Moroyama-machi, Iruma-gun, Saitama, 350-0495, Japan; Department of Pathology, Kanagawa Cardiovascular & Respiratory Center, 6-16-1, Tomiokahigashi, Kanazawa-ku, Yokohama City, Kanagawa, 236-0051, Japan
| | - Kensuke Kataoka
- Department of Respiratory Medicine and Allergy, Tosei General Hospital, 160, Nishioiwake-cho, Seto City, Aichi, 489-8642, Japan
| | - Yasuhiko Yamano
- Department of Respiratory Medicine and Allergy, Tosei General Hospital, 160, Nishioiwake-cho, Seto City, Aichi, 489-8642, Japan
| | - Yasuhiro Kondoh
- Department of Respiratory Medicine and Allergy, Tosei General Hospital, 160, Nishioiwake-cho, Seto City, Aichi, 489-8642, Japan
| | - Takeshi Johkoh
- Department of Radiology, Kansai Rosai Hospital, 3-1-69, Inabaso, Amagasaki City, Hyogo, 660-8511, Japan
| | - Junya Fukuoka
- Department of Pathology Informatics, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1, Sakamoto, Nagasaki, 852-8523, Japan; Department of Pathology, Kameda Medical Center, 929, Higashi-cho, Kamogawa City, Chiba, 296-0041, Japan.
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Liu W, Liu D, Cui T, Wang Y, Zhou S, Tian F, Yang K, Wang W, Bi L, Fan K, Li L, Wang H, Zhang XD. Atomic Artificial Enzyme for Acute and Chronic Pneumonia. Adv Healthc Mater 2025; 14:e2402364. [PMID: 39248150 DOI: 10.1002/adhm.202402364] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Revised: 08/30/2024] [Indexed: 09/10/2024]
Abstract
Pneumonia involves complex immunological and pathological processes leading to pulmonary dysfunction, which can be life-threatening yet lacks effective specialized medications. Natural enzymes can be used as biological agents for the treatment of oxidative stress-related diseases, but limiting to catalytic and environmental stability as well as high cost. Herein, an artificial enzyme, gold nanoclusters (Au NCs) with excellent stability, bioactivity, and renal clearance can be used as the next-generation biological agents for acute lung injury (ALI) and allergic lung disease (ALD). The Au25 clusters can mimic catalase (CAT) and glutathione peroxidase (GPx), and the Km of Au24Er1 with H2O2 reaches 1.28 mM, about 22 times higher than natural CAT (≈28.8 mM). The clusters inhibit the oxidative stress in the mitochondria and promote the synthesis of adenosine triphosphate (ATP). The molecular mechanism shows that the TLR4/MyD88/NF-κB pathway and M1 macrophage-mediated inflammatory response are suppressed in ALI and the Th1/Th2 imbalance in ovalbumin (OVA)-induced ALD is rescued. Further, the clusters can notably improve lung function in both ALI and ALD models which paves the way for immunomodulation and intervention for lung injury and can be used as a substitute for natural enzymes and potential biopharmaceuticals in the treatment of various types of pneumonia.
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Affiliation(s)
- Wei Liu
- Tianjin Key Laboratory of Brain Science and Neural Engineering, Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, 300072, China
- Tianjin Key Laboratory of Birth Defects for Prevention and Treatment, Tianjin Children's Hospital (Tianjin University Children's Hospital), Tianjin, 300134, China
| | - Di Liu
- Tianjin Key Laboratory of Brain Science and Neural Engineering, Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, 300072, China
| | - Tianyi Cui
- State Key Laboratory of Modern Chinese Medicine, Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, 301616, China
| | - Yili Wang
- Tianjin Key Laboratory of Brain Science and Neural Engineering, Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, 300072, China
| | - Sufei Zhou
- Tianjin Key Laboratory of Brain Science and Neural Engineering, Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, 300072, China
| | - Fangzhen Tian
- Tianjin Key Laboratory of Brain Science and Neural Engineering, Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, 300072, China
| | - Ke Yang
- State Key Laboratory of Modern Chinese Medicine, Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, 301616, China
| | - Wei Wang
- Tianjin Key Laboratory of Birth Defects for Prevention and Treatment, Tianjin Children's Hospital (Tianjin University Children's Hospital), Tianjin, 300134, China
| | - Lewei Bi
- Tianjin Key Laboratory of Birth Defects for Prevention and Treatment, Tianjin Children's Hospital (Tianjin University Children's Hospital), Tianjin, 300134, China
| | - Kelong Fan
- CAS Engineering Laboratory for Nanozyme, Key Laboratory of Biomacromolecules (CAS), CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
| | - Lan Li
- State Key Laboratory of Modern Chinese Medicine, Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, 301616, China
| | - Hao Wang
- Tianjin Key Laboratory of Brain Science and Neural Engineering, Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, 300072, China
| | - Xiao-Dong Zhang
- Tianjin Key Laboratory of Brain Science and Neural Engineering, Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, 300072, China
- Department of Physics and Tianjin Key Laboratory of Low Dimensional Materials Physics and Preparing Technology, School of Sciences, Tianjin University, Tianjin, 300350, China
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Courtemanche O, Huppé CA, Blais-Lecours P, Maranda C, Morissette MC, Blanchet MR, Dion G, Marsolais D. Ex Vivo Overactivation of Lymphocyte Subsets in Fibrotic Hypersensitivity Pneumonitis Is Blunted by a Sphingosine-1-Phosphate Receptor Ligand. Int J Mol Sci 2025; 26:3197. [PMID: 40243992 PMCID: PMC11989070 DOI: 10.3390/ijms26073197] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2025] [Revised: 03/21/2025] [Accepted: 03/24/2025] [Indexed: 04/18/2025] Open
Abstract
Lymphocytes are central to the pathogenesis of hypersensitivity pneumonitis and a strong body of evidence supports that lymphocytes are modulated by sphingosine-1-phosphate receptor-modifying drugs. This exploratory study aimed to determine if a pharmacological sphingosine-1-phosphate receptor ligand interfered with the activation of lymphocytes obtained from fibrotic hypersensitivity pneumonitis patients. Peripheral blood mononuclear cells of 12 patients and 10 control subjects were submitted to CD3/CD28 stimulation, isolated B cells were incubated with a TLR9 ligand; and we tested how these stimulations were impacted by ozanimod, a sphingosine-1-phosphate receptor ligand. T cell and B cell subsets from patients overexpressed CD69 and cytokines such as TNF and IL-4 in response to CD3/CD28 stimulation, compared to controls. In patients with fibrotic hypersensitivity pneumonitis, ozanimod alleviated CD3/CD28 induction of CD69, IL-4, and TNF in CD8, but not CD4 T cells. In isolated B cells stimulated with a TLR9 ligand, ozanimod reduced cell surface expression of CD69, CD86, and CD40, as well as TNF and IL-6 accumulation in supernatant. We conclude that lymphocyte subsets are functionally impacted in patients with fibrotic hypersensitivity pneumonitis and that ozanimod can interfere ex vivo with the overactivation of B cells and CD8 T cells in response to specific stimuli.
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Affiliation(s)
- Olivier Courtemanche
- Centre de recherche de l’Institut Universitaire de cardiologie et de pneumologie de Québec, 2725 Chemin Sainte-Foy, Quebec City, QC G1V 4G5, Canada; (O.C.); (C.-A.H.); (P.B.-L.); (C.M.); (M.C.M.); (M.-R.B.); (G.D.)
| | - Carole-Ann Huppé
- Centre de recherche de l’Institut Universitaire de cardiologie et de pneumologie de Québec, 2725 Chemin Sainte-Foy, Quebec City, QC G1V 4G5, Canada; (O.C.); (C.-A.H.); (P.B.-L.); (C.M.); (M.C.M.); (M.-R.B.); (G.D.)
| | - Pascale Blais-Lecours
- Centre de recherche de l’Institut Universitaire de cardiologie et de pneumologie de Québec, 2725 Chemin Sainte-Foy, Quebec City, QC G1V 4G5, Canada; (O.C.); (C.-A.H.); (P.B.-L.); (C.M.); (M.C.M.); (M.-R.B.); (G.D.)
| | - Cloé Maranda
- Centre de recherche de l’Institut Universitaire de cardiologie et de pneumologie de Québec, 2725 Chemin Sainte-Foy, Quebec City, QC G1V 4G5, Canada; (O.C.); (C.-A.H.); (P.B.-L.); (C.M.); (M.C.M.); (M.-R.B.); (G.D.)
| | - Mathieu C. Morissette
- Centre de recherche de l’Institut Universitaire de cardiologie et de pneumologie de Québec, 2725 Chemin Sainte-Foy, Quebec City, QC G1V 4G5, Canada; (O.C.); (C.-A.H.); (P.B.-L.); (C.M.); (M.C.M.); (M.-R.B.); (G.D.)
- Department of Medicine, Faculty of Medicine, Université Laval, Quebec City, QC G1V 0A6, Canada
| | - Marie-Renée Blanchet
- Centre de recherche de l’Institut Universitaire de cardiologie et de pneumologie de Québec, 2725 Chemin Sainte-Foy, Quebec City, QC G1V 4G5, Canada; (O.C.); (C.-A.H.); (P.B.-L.); (C.M.); (M.C.M.); (M.-R.B.); (G.D.)
- Department of Medicine, Faculty of Medicine, Université Laval, Quebec City, QC G1V 0A6, Canada
| | - Geneviève Dion
- Centre de recherche de l’Institut Universitaire de cardiologie et de pneumologie de Québec, 2725 Chemin Sainte-Foy, Quebec City, QC G1V 4G5, Canada; (O.C.); (C.-A.H.); (P.B.-L.); (C.M.); (M.C.M.); (M.-R.B.); (G.D.)
| | - David Marsolais
- Centre de recherche de l’Institut Universitaire de cardiologie et de pneumologie de Québec, 2725 Chemin Sainte-Foy, Quebec City, QC G1V 4G5, Canada; (O.C.); (C.-A.H.); (P.B.-L.); (C.M.); (M.C.M.); (M.-R.B.); (G.D.)
- Department of Medicine, Faculty of Medicine, Université Laval, Quebec City, QC G1V 0A6, Canada
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Fu X, Liu C, Gong P, Gao Z. Paprika-Induced Hypersensitivity Pneumonitis: A Report of a Rare Case. Cureus 2025; 17:e80195. [PMID: 40196094 PMCID: PMC11973407 DOI: 10.7759/cureus.80195] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/06/2025] [Indexed: 04/09/2025] Open
Abstract
Hypersensitivity pneumonitis (HP) is an interstitial lung disease caused by exposure to environmental antigens in susceptible individuals. It is a type IV hypersensitivity reaction. The antigens involved in HP are numerous, but their identification is challenging. We report the first clinical case of HP associated with exposure to paprika. The diagnosis was confirmed based on the patient's exposure history, chest imaging, bronchoalveolar lavage fluid analysis, and pathological findings. Avoidance of antigens and treatment with glucocorticoids resulted in symptom relief. Follow-up chest imaging showed no ideal improvement; immunosuppressants or antifibrotic drugs may be considered in combination if necessary. The case highlights that individuals working in paprika production and processing should take preventive measures to avoid chronic pulmonary fibrosis.
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Affiliation(s)
- Xinyu Fu
- Department of Pulmonary and Critical Care Medicine, Peking University People's Hospital, Beijing, CHN
| | - Chunyu Liu
- Department of Pulmonary and Critical Care Medicine, Peking University People's Hospital, Beijing, CHN
| | - Pihua Gong
- Department of Pulmonary and Critical Care Medicine, Peking University People's Hospital, Beijing, CHN
| | - Zhancheng Gao
- Department of Pulmonary and Critical Care Medicine, Peking University People's Hospital, Beijing, CHN
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5
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Spalgais S, Ranga V, Mavi AK, Kumar R. House dust protein level of pigeon drooping and feather in environmental bird exposure-related hypersensitivity pneumonitis "A pilot study". Lung India 2025; 42:11-15. [PMID: 39718910 PMCID: PMC11789959 DOI: 10.4103/lungindia.lungindia_205_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2024] [Revised: 09/24/2024] [Accepted: 10/14/2024] [Indexed: 12/26/2024] Open
Abstract
BACKGROUND Bird fancier's disease is a type of HP occurring due to exposure to bird's antigen. The diagnosis is quite difficult as it requires the identification of an inciting agent with findings of HRCT and lung biopsy. The exposure is usually done by history with antigen-specific IgG and/or specific inhalational challenge testing. The study aimed to investigate the role of pigeon allergens in house dust in bird exposure-related HP patients. METHODS This was a descriptive, mixed-method observational study. We retrospectively screened all the files of HP patients for exposure history and pigeon-specific IgG of one-year duration. Finally, Finally house dust from 18 cases with HP was collected for analysis of concentration of pigeon droppings and feather proteins. RESULTS The mean age was 47.8 ± 11.5 years with 78% being female. The median duration of symptoms was 1.75 years with a median exposure history to pigeons of 7 years. The level of specific IgG was raised in 11 (60%) patients with a mean level of 50.6 ± 39.5. The concentration of pigeon-drooping protein was present in all the dust samples with a mean of 17.6 ± 5.6 μg/mg. The highest concentration was 27 μg/mg and the lowest of 9 μg/mg. The concentration of pigeon father protein was present in nearly 50% of the dust sample with a mean of 5.6 ± 6.7 μg/mg and the highest concentration was 15.8 μg/mg. CONCLUSION The confirmation history of exposure in bird exposure-related HP is difficult because bird antigen exposure can be presents anywhere. The house dust bird protein concentration measurement is a simple, non-invasive, adjunct test for confirmation of bird exposure.
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Affiliation(s)
- Sonam Spalgais
- Department of Pulmonary Medicine, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India
| | - Vikrant Ranga
- Respiratory Medicine, Dr. Prem Superspeciality and Cancer Hospital, Panipat, Haryana, India
| | - Anil K. Mavi
- Department of Pulmonary Medicine, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India
- Department of Botany and Life Sciences, Sri Aurobindo College, University of Delhi, Delhi, India
| | - Raj Kumar
- Department of Pulmonary Medicine, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India
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Collins BF, Raghu G. Hypersensitivity pneumonitis: A high index of clinical suspicion is key for early diagnosis and successful treatment. Respirology 2025; 30:10-12. [PMID: 39581850 DOI: 10.1111/resp.14858] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2024] [Accepted: 11/13/2024] [Indexed: 11/26/2024]
Abstract
See related article
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Affiliation(s)
- Bridget F Collins
- Center for Interstitial lung diseases; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, Seattle, Washington, USA
- Evergreen Health Pulmonary Care, Kirkand, Washington, USA
| | - Ganesh Raghu
- Center for Interstitial lung diseases; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, Seattle, Washington, USA
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Koschel D, Behr J, Berger M, Bonella F, Hamer O, Joest M, Jonigk D, Kreuter M, Leuschner G, Nowak D, Raulf M, Rehbock B, Schreiber J, Sitter H, Theegarten D, Costabel U. [Diagnosis and Treatment of Hypersensitivity Pneumonitis - S2k Guideline of the German Respiratory Society and the German Society for Allergology and Clinical Immunology]. Pneumologie 2024; 78:963-1002. [PMID: 39227017 DOI: 10.1055/a-2369-8458] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/05/2024]
Abstract
Hypersensitivity pneumonitis (HP) is an immune-mediated interstitial lung disease (ILD) in sensitized individuals caused by a large variety of inhaled antigens. The clinical form of acute HP is often misdiagnosed, while the chronic form, especially the chronic fibrotic HP, is difficult to differentiate from other fibrotic ILDs. The present guideline for the diagnosis and treatment of HP replaces the former German recommendations for the diagnosis of HP from 2007 and is amended explicitly by the issue of the chronic fibrotic form, as well as by treatment recommendations for the first time. The evidence was discussed by a multidisciplinary committee of experts. Then, recommendations were formulated for twelve questions on important issues of diagnosis and treatment strategies. Recently published national and international guidelines for ILDs and HP were considered. Detailed background information on HP is useful for a deeper insight into HP and the handling of the guideline.
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Affiliation(s)
- Dirk Koschel
- Abteilung Innere Medizin und Pneumologie, Fachkrankenhaus Coswig, Lungenzentrum, Coswig, Deutschland
- Bereich Pneumologie, Medizinische Klinik 1, Universitätsklinikum Carl Gustav Carus, TU Dresden, Dresden, Deutschland
- Ostdeutsches Lungenzentrum (ODLZ), Coswig/Dresden, Deutschland
| | - Jürgen Behr
- Medizinische Klinik und Poliklinik V, LMU Klinikum der Universität München, München, Deutschland
- Deutsches Zentrum für Lungenforschung, Gießen, Deutschland
| | - Melanie Berger
- Lungenklinik, Kliniken der Stadt Köln gGmbH, Köln
- Lehrstuhl für Pneumologie, Universität Witten/Herdecke, Fakultät für Gesundheit, Köln, Deutschland
| | - Francesco Bonella
- Zentrum für interstitielle und seltene Lungenerkrankungen, Ruhrlandklinik, Universitätsmedizin Essen, Essen, Deutschland
| | - Okka Hamer
- Institut für Röntgendiagnostik, Universitätsklinikum Regensburg, Regensburg, Deutschland
- Abteilung für Radiologie, Lungenfachklinik Donaustauf, Donaustauf, Deutschland
| | - Marcus Joest
- Praxis für Pneumologie und Allergologie, Bonn, Deutschland
| | - Danny Jonigk
- Deutsches Zentrum für Lungenforschung, Gießen, Deutschland
- Institut für Pathologie, RWTH Aachen, Universität Aachen, Aachen, Deutschland
| | - Michael Kreuter
- Lungenzentrum Mainz, Klinik für Pneumologie, Beatmungs- und Schlafmedizin, Marienhaus Klinikum Mainz und Klinik für Pneumologie, ZfT, Universitätsmedizin Mainz, Mainz, Deutschland
| | - Gabriela Leuschner
- Medizinische Klinik und Poliklinik V, LMU Klinikum der Universität München, München, Deutschland
- Deutsches Zentrum für Lungenforschung, Gießen, Deutschland
| | - Dennis Nowak
- Institut und Poliklinik für Arbeits-, Sozial- und Umweltmedizin, LMU München, München, Deutschland
| | - Monika Raulf
- Abteilung Kompetenz-Zentrum Allergologie/Immunologie, Institut für Prävention und Arbeitsmedizin der DGUV, Institut der Ruhr-Universität Bochum (IPA), Bochum, Deutschland
| | - Beate Rehbock
- Privatpraxis für Diagnostische Radiologie und Begutachtung, Berlin, Deutschland
| | - Jens Schreiber
- Universitätsklinik für Pneumologie, Universitätsklinikum Magdeburg, Magdeburg, Deutschland
| | - Helmut Sitter
- Institut für Theoretische Chirurgie, Philipps-Universität Marburg, Marburg, Deutschland
| | - Dirk Theegarten
- Institut für Pathologie, Universitätsklinikum Essen, Essen, Deutschland
| | - Ulrich Costabel
- Zentrum für interstitielle und seltene Lungenerkrankungen, Ruhrlandklinik, Universitätsmedizin Essen, Essen, Deutschland
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8
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Barnes H, Corte TJ, Keir G, Khor YH, Limaye S, Wrobel JP, Veitch E, Harrington J, Dowman L, Beckert L, Milne D, De Losa R, Cooper WA, Bell PT, Balakrishnan P, Troy LK. Diagnosis and management of hypersensitivity pneumonitis in adults: A position statement from the Thoracic Society of Australia and New Zealand. Respirology 2024; 29:1023-1046. [PMID: 39467777 DOI: 10.1111/resp.14847] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2024] [Accepted: 10/10/2024] [Indexed: 10/30/2024]
Abstract
Hypersensitivity pneumonitis (HP) is an immune-mediated interstitial lung disease (ILD) relating to specific occupational, environmental or medication exposures. Disease behaviour is influenced by the nature of exposure and the host response, with varying degrees of lung inflammation and fibrosis seen within individuals. The differentiation of HP from other ILDs is important due to distinct causes, pathophysiology, prognosis and management implications. This Thoracic Society of Australia and New Zealand (TSANZ) position statement aims to provide an up-to-date summary of the evidence for clinicians relating to the diagnosis and management of HP in adults, in the Australian and New Zealand context. This document highlights recent relevant findings and gaps in the literature for which further research is required.
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Affiliation(s)
- Hayley Barnes
- Department of Respiratory Medicine, Alfred Hospital, Melbourne, Victoria, Australia
- Respiratory Research@Alfred, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia
- Monash Centre for Occupational and Environmental Health, Monash University, Melbourne, Victoria, Australia
| | - Tamera J Corte
- Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
- Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia
- NHMRC Centre of Research Excellence in Pulmonary Fibrosis, Camperdown, New South Wales, Australia
- Institute for Academic Medicine, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
| | - Gregory Keir
- Department of Respiratory and Sleep Medicine, Princess Alexandra Hospital, Brisbane, Queensland, Australia
- Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
| | - Yet H Khor
- Respiratory Research@Alfred, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia
- Department of Respiratory and Sleep Medicine, Austin Health, Heidelberg, Victoria, Australia
- Institute for Breathing and Sleep, Heidelberg, Victoria, Australia
- Faculty of Medicine, University of Melbourne, Melbourne, Victoria, Australia
| | - Sandhya Limaye
- Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia
- Department of Immunology, Concord Hospital, Concord, New South Wales, Australia
| | - Jeremy P Wrobel
- Advanced Lung Disease Unit, Fiona Stanley Hospital, Perth, Western Australia, Australia
- School of Medicine, University of Notre Dame Australia, Fremantle, Western Australia, Australia
| | - Elizabeth Veitch
- Respiratory Department, Concord Repatriation General Hospital, Concord, New South Wales, Australia
- Faculty of Medicine, Macquarie University, Macquarie Park, New South Wales, Australia
| | - John Harrington
- Asthma and Breathing Research Program, The Hunter Medical Research Institute (HMRI), New Lambton, New South Wales, Australia
- Department of Sleep and Respiratory Medicine, John Hunter Hospital, Newcastle, New South Wales, Australia
| | - Leona Dowman
- Respiratory Research@Alfred, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia
- Department of Respiratory and Sleep Medicine, Austin Health, Heidelberg, Victoria, Australia
- Institute for Breathing and Sleep, Heidelberg, Victoria, Australia
| | - Lutz Beckert
- Department of Respiratory Medicine, Te Whatu Ora, Panui Canterbury, New Zealand
- Department of Medicine, University of Otago, Christchurch, New Zealand
| | - David Milne
- Department of Radiology, Te Toka Tumai, Auckland, New Zealand
| | - Rebekah De Losa
- Respiratory Medicine, Northern Hospital, Epping, Victoria, Australia
| | - Wendy A Cooper
- Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia
- Institute for Academic Medicine, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
- Department of Tissue Pathology and Diagnostic Oncology, NSW Health Pathology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
- School of Medicine, Western Sydney University, Sydney, New South Wales, Australia
| | - Peter T Bell
- Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
- Department of Respiratory and Sleep Medicine, Sunshine Coast University Hospital, Sunshine Coast, Queensland, Australia
| | - Pradeep Balakrishnan
- Department of Medicine, St John of God Midland Public Hospital, Perth, Western Australia, Australia
- UWA Medical School, Division of Internal Medicine, University of Western Australia, Perth, Western Australia, Australia
| | - Lauren K Troy
- Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
- Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia
- NHMRC Centre of Research Excellence in Pulmonary Fibrosis, Camperdown, New South Wales, Australia
- Institute for Academic Medicine, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
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9
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Vongvivitpatana TS, Nambiar AM. A Low Forced Vital Capacity (FVC)/Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) Ratio Increases Clinical Suspicion for Fibrotic Hypersensitivity Pneumonitis (FHP) Over Idiopathic Pulmonary Fibrosis (IPF). Cureus 2024; 16:e73008. [PMID: 39634966 PMCID: PMC11617056 DOI: 10.7759/cureus.73008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/19/2024] [Indexed: 12/07/2024] Open
Abstract
Background and objective Fibrotic Hypersensitivity Pneumonitis (FHP) and idiopathic pulmonary fibrosis (IPF) are interstitial lung diseases (ILDs) that are challenging to differentiate with prognostic and therapeutic implications. Clinical observations suggest that patients with FHP may have a lower baseline ratio of forced vital capacity (FVC) to the diffusing capacity of the lung for carbon monoxide (DLCO), or FVC/DLCO (F/D) ratio, than patients with IPF. In light of this, we aimed to determine whether patients with FHP have a significantly lower baseline F/D ratio than patients with IPF. Methods A retrospective chart review was performed at a single academic ILD center. Patients with a probable or definite diagnosis of FHP or IPF were considered for inclusion, while patients with poor-quality pulmonary function tests (PFTs) were excluded. The data collected included demographics, diagnosis modality, FVC and DLCO values within six months of diagnosis, as well as hemoglobin levels within three months of PFTs. Baseline F/D ratios were calculated using each patient's FVC percentage of predicted value divided by the DLCO percentage of predicted value adjusted for hemoglobin when available. One-tailed independent two-sample T-tests were performed. Results Eighty-nine patients met the inclusion criteria: 39 (44%) with FHP and 50 (56%) with IPF. The mean baseline F/D ratio was significantly lower for patients with FHP (M = 1.24, 95% CI: 1.14, 1.33) than for patients with IPF (M = 1.44, 95% CI: 1.31, 1.57, T(87) = 2.23, p = 0.014). A secondary analysis excluding patients with pulmonary hypertension and resting hypoxemia was performed, yielding 72 patients: 32 (44%) with FHP and 40 (56%) with IPF. The mean baseline F/D ratio was significantly lower for patients with FHP (M = 1.22, 95% CI: 1.12, 1.31) compared to patients with IPF (M = 1.37, 95% CI: 1.27, 1.46, T (70) = 2.37, p = 0.01). Conclusions In patients with probable to definite FHP versus IPF, the baseline F/D ratio was significantly lower in patients with FHP, even after excluding patients with coexisting pulmonary hypertension and resting hypoxemia. A lower baseline F/D ratio may be a novel, clinic-ready index to heighten clinical suspicion for FHP compared to IPF. Further larger prospective studies are needed to validate our findings.
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Affiliation(s)
- Tannam S Vongvivitpatana
- Internal Medicine, University of Colorado, Denver, USA
- Internal Medicine, University of Texas Health Science Center at San Antonio, San Antonio, USA
| | - Anoop M Nambiar
- Medicine/Pulmonary Disease, University of Texas Health Science Center at San Antonio, San Antonio, USA
- Internal Medicine/Pulmonary Disease, Audie L. Murphy VA Hospital, South Texas Veterans Health Care System, San Antonio, USA
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10
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Swaminathan AC, McFatrich M, Mkumba L, Wright L, Redlich CA, Snyder LD, Reeve BB, Patel D, Gulati M. Development and evaluation of a questionnaire to capture environmental and occupational inhalational exposures in adults with fibrotic interstitial lung disease. Respir Res 2024; 25:372. [PMID: 39407223 PMCID: PMC11481565 DOI: 10.1186/s12931-024-03000-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Accepted: 10/02/2024] [Indexed: 10/19/2024] Open
Abstract
BACKGROUND Identification of exposures in patients with interstitial lung diseases (ILDs) is essential for diagnosis and management and can be facilitated through the use of exposure questionnaires. However, for most ILDs, a patient-focused questionnaire is lacking. Cognitive interviewing is a methodology used to evaluate sources of understanding and misunderstanding in a questionnaire and to provide evidence of content validity. We developed and refined a new exposure questionnaire for patients with fibrotic ILDs by using cognitive interviewing to establish its understandability and content validity. METHODS An exposure assessment questionnaire was developed by a multidisciplinary team. Cognitive interviews with 24 patients with fibrosing ILDs were conducted by trained interviewers over the phone or Zoom using a semi-structured interview guide. The questionnaire was amended based on the interviewers' interpretation of sources of misunderstanding. The revised questionnaire was tested in a second round of cognitive interviews with a different group of 24 patients. RESULTS Among the 48 patients who completed interviews, mean age was 61 years, 58.3% were male and 75.0% were white. Based on the first round of cognitive interviews, the multidisciplinary team modified the questions, organization, and instructions of the questionnaire to facilitate recall, adjust for exposures that were frequently misunderstood or required clarification, and focus on clinically relevant exposures. The revised questionnaire performed well in the second round of interviews. CONCLUSION An exposure questionnaire, developed with input from patients, can be used to assess clinically relevant exposures in adults with fibrosing ILDs. This is the first questionnaire for all types of fibrosing ILD to have undergone content validation.
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Affiliation(s)
- Aparna C Swaminathan
- Duke Clinical Research Institute, Durham, NC, USA.
- Duke University Medical Center, Durham, NC, 27710, USA.
| | | | - Laura Mkumba
- Duke University School of Medicine, Durham, NC, USA
| | | | | | - Laurie D Snyder
- Duke Clinical Research Institute, Durham, NC, USA
- Duke University Medical Center, Durham, NC, 27710, USA
| | - Bryce B Reeve
- Duke Clinical Research Institute, Durham, NC, USA
- Duke University School of Medicine, Durham, NC, USA
| | - Divya Patel
- Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, CT, USA
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11
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Lemieszek MK, Chojnacki M, Paśnik I, Gawryś W, Wilczyńska A, Leśniowska I, Anisiewicz J. Beneficial Impact of Inhaled 25(OH)-Vitamin D3 and 1,25(OH)2-Vitamin D3 on Pulmonary Response in the Murine Model of Hypersensitivity Pneumonitis. Int J Mol Sci 2024; 25:10289. [PMID: 39408616 PMCID: PMC11476509 DOI: 10.3390/ijms251910289] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Revised: 09/18/2024] [Accepted: 09/18/2024] [Indexed: 10/20/2024] Open
Abstract
Despite numerous scientific reports on the negative impact of vitamin D3 deficiency on many respiratory diseases, little is known about the influence of this phenomenon on the development and progression of hypersensitivity pneumonitis (HP). The presented study is an attempt to shed light on this occurrence. The research was performed on mouse strain C57BL/6J exposed to the antigen of Pantoea agglomerans (etiological factor of HP). To induce vitamin D3 deficiency, mice received a diet with a 10 times lower amount of cholecalciferol than the main control group. VD3-deficient mice inhaled 25(OH)-VD3 or 1,25(OH)2-VD3 used separately or with SE-PA. At the beginning of the experiment and after 14 and 28 days of inhalation, respiratory function was examined using whole-body plethysmography. Moreover, at indicated time points, mice were sacrificed and samples collected for histological examination, flow cytometry, and ELISA. The performed study revealed that inhalations with 25(OH)-VD3 and 1,25(OH)2-VD3 effectively eliminated most of the negative changes in the respiratory system caused by vitamin D3 deficiency by restoring the physiological concentration of 1,25(OH)2-VD3 in the body. VD3-deficient mice which inhaled P. agglomerans antigen and vitamin D3 metabolites also demonstrated the ability of the tested compounds to eliminate, or at least weaken, the negative effects of the HP causative factor and desired effect, including improvement of respiratory functions and attenuation of inflammation and signs of fibrosis. The obtained results suggested that the beneficial influence of inhaled vitamin D3 metabolites on HP development was associated with the restoration of the physiological concentration of 1,25(OH)2-VD3 in the pulmonary compartments in VD3-deficient mice.
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Affiliation(s)
- Marta Kinga Lemieszek
- Department of Medical Biology, Institute of Rural Health, Jaczewskiego 2, 20-090 Lublin, Poland; (M.C.); (W.G.); (A.W.)
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12
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Rafique M, Arslan F, Khan J, Zaki S, Hussain A. Hypersensitivity Pneumonitis: An Interesting Case of Acute Shortness of Breath in a Young Patient. Cureus 2024; 16:e68683. [PMID: 39238923 PMCID: PMC11375757 DOI: 10.7759/cureus.68683] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/04/2024] [Indexed: 09/07/2024] Open
Abstract
Hypersensitivity pneumonitis (HP) is a rare disease caused by an inflammation of the distal airway caused by an immune response to inhaled allergens. The clinical presentation and radiological and histological findings can overlap with other pulmonary conditions such as idiopathic pulmonary fibrosis. Therefore, it is essential to consider focused assessment for the patient if a diagnosis of HP is suspected. We present a case involving a young female patient who presented with symptoms of cough, flu-like illness, and dyspnea. Subsequent investigations revealed a diagnosis of nonfibrotic HP. The patient experienced acute respiratory failure and was managed with high-flow oxygen therapy. A detailed investigation determined that the patient's prior exposure to pet parrots at home was a significant factor. Following treatment with steroids and counseling regarding the removal of parrots from the home environment, the patient's condition improved, and she was successfully weaned off of oxygen therapy. This case underscores the importance of a comprehensive social history in evaluating common complaints such as dyspnea. The rarity of parrot-induced HP related to the patient's age, and exposure warrants attention.
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Affiliation(s)
| | | | - Joohi Khan
- Acute Medicine, Pinderfields Hospital, Wakefield, GBR
| | - Sameh Zaki
- General Practice, Pinderfields Hospital, Wakefield, GBR
| | - Ali Hussain
- Acute Medicine, Pinderfields Hospital, Wakefield, GBR
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13
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Deutsch K, Lewandowska KB, Kowalik A, Bartoszuk I, Radwan-Röhrenschef P, Sobiecka M, Dybowska M, Tomkowski WZ, Szturmowicz M. Does a Type of Inciting Antigen Correlate with the Presence of Lung Fibrosis in Patients with Hypersensitivity Pneumonitis? J Clin Med 2024; 13:5074. [PMID: 39274286 PMCID: PMC11396382 DOI: 10.3390/jcm13175074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2024] [Revised: 08/23/2024] [Accepted: 08/23/2024] [Indexed: 09/16/2024] Open
Abstract
Introduction: Hypersensitivity pneumonitis (HP) is an interstitial inflammatory lung disease that develops as a result of exposition to various, mostly organic antigens. In some patients, fibrotic HP is diagnosed. Factors predisposing to the development of fibrotic lung disease in HP patients are not well documented in the literature. The genetic susceptibility of the patient, type of inciting antigen, and type of exposure, as well as various demographic and clinical variables, may influence the fibrotic process. Aim: The aim of the present study was to investigate whether the type of inciting antigen increases the risk of fibrotic lung disease in HP patients. Methods: Clinical data of consecutive patients with HP diagnosed between 2019 and 2023 were retrospectively reviewed. The exposition to the inciting antigens was investigated by the standardized questionnaire. Recent HP classification into fibrotic (fHP) and non-fibrotic (non-fHP) types was applied. Results: Sixty-six patients diagnosed with HP were analyzed. All patients filled out the exposure questionnaire, and 62 (94%) reported at least one possible exposure. The most prevalent exposures reported were avian, water systems, feather duvets, and hay/straw. Exposure to avian antigens as well as to coal/biomass heating were significantly more prevalent among patients with fHP compared to those with non-fHP (70% vs. 40%, p = 0.03 and 27% vs. 5%, p = 0.04, respectively). Nevertheless, in the multivariate analysis, older age at diagnosis was the only factor influencing the development of fHP (OR 1.064, 95% CI 1.004 to 1.138, p = 0.04). Reported avian antigen exposure correlated well with positive precipitins to avian antigens, whereas no correlation was found between hay/straw exposure and positive antibodies to termophilic actinomycetes. Conclusions: Exposure to birds and coal heating was the most frequently present factor in subjects with fHP, but only older age at diagnosis remained a significant fHP predictor in the multifactor analysis.
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Affiliation(s)
- Kamila Deutsch
- 1st Department of Lung Diseases, National Research Institute of Tuberculosis and Lung Diseases, Płocka 26, 01-138 Warsaw, Poland
| | - Katarzyna B Lewandowska
- 1st Department of Lung Diseases, National Research Institute of Tuberculosis and Lung Diseases, Płocka 26, 01-138 Warsaw, Poland
| | - Agata Kowalik
- 1st Department of Lung Diseases, National Research Institute of Tuberculosis and Lung Diseases, Płocka 26, 01-138 Warsaw, Poland
| | - Iwona Bartoszuk
- 1st Department of Lung Diseases, National Research Institute of Tuberculosis and Lung Diseases, Płocka 26, 01-138 Warsaw, Poland
| | - Piotr Radwan-Röhrenschef
- 1st Department of Lung Diseases, National Research Institute of Tuberculosis and Lung Diseases, Płocka 26, 01-138 Warsaw, Poland
| | - Małgorzata Sobiecka
- 1st Department of Lung Diseases, National Research Institute of Tuberculosis and Lung Diseases, Płocka 26, 01-138 Warsaw, Poland
| | - Małgorzata Dybowska
- 1st Department of Lung Diseases, National Research Institute of Tuberculosis and Lung Diseases, Płocka 26, 01-138 Warsaw, Poland
| | - Witold Z Tomkowski
- 1st Department of Lung Diseases, National Research Institute of Tuberculosis and Lung Diseases, Płocka 26, 01-138 Warsaw, Poland
| | - Monika Szturmowicz
- 1st Department of Lung Diseases, National Research Institute of Tuberculosis and Lung Diseases, Płocka 26, 01-138 Warsaw, Poland
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14
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Zhan S, Li S, Cao Y, Liu D, Feng J. Value of bronchoalveolar lavage fluid metagenomic next-generation sequencing in acute exacerbation of fibrosing interstitial lung disease: an individualized treatment protocol based on microbiological evidence. BMC Pulm Med 2024; 24:400. [PMID: 39164677 PMCID: PMC11337881 DOI: 10.1186/s12890-024-03216-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Accepted: 08/13/2024] [Indexed: 08/22/2024] Open
Abstract
BACKGROUND Acute exacerbation of fibrosing interstitial lung diseases (AE-ILD) is a serious life-threatening event per year. Methylprednisolone and/or immunosuppressive agents (ISA) are a mainstay in any regimen, under the premise that pulmonary infection has been promptly identified and controlled. We investigated the value of bronchoalveolar lavage fluid (BALF) metagenomic next-generation sequencing (mNGS) on the treatment adjustment of AE-ILD. METHODS We conducted a cross-sectional observational study. All data were collected prospectively and retrospectively analyzed. We included fifty-six patients with AE-ILD and nineteen stable ILD who underwent BALF mNGS at the beginning of admission. RESULTS Patients with a variety of ILD classification were included. Connective-tissue disease related ILD (CTD-ILD) occupy the most common underlying non-idiopathic pulmonary fibrosis (non-IPF). The infection-triggered AE accounted for 39.29%, with the majority of cases being mixed infections. The microorganisms load in the AE-ILD group was significantly higher. After adjusted by mNGS, the therapy coverage number of pathogens was significantly higher compared to the initial treatment (p < 0.001). After treatment, the GGO score and the consolidation score were significantly lower during follow up in survivors (1.57 ± 0.53 vs. 2.38 ± 0.83 with p < 0.001, 1.11 ± 0.24 vs. 1.49 ± 0.47 with p < 0.001, respectively). Some detected microorganisms, such as Tropheryma whipplei, Mycobacterium, Aspergillus, and mixed infections were difficult to be fully covered by empirical medication. BALF mNGS was also very helpful for excluding infections and early administration of methylprednisolone and/or ISA. CONCLUSIONS mNGS has been shown to be a useful tool to determine pathogens in patients with AE-ILD, the results should be fully analyzed. The comprehensive treatment protocol based on mNGS has been shown crucial in AE-ILD patients.
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Affiliation(s)
- Siyu Zhan
- Department of Respiratory and Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, 300052, China
| | - Shuo Li
- Department of Respiratory and Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, 300052, China
| | - Yaoqian Cao
- Department of Respiratory and Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, 300052, China
| | - Dan Liu
- Department of Respiratory and Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, 300052, China.
| | - Jing Feng
- Department of Respiratory and Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, 300052, China.
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15
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Yatera K, Nishida C. Contemporary Concise Review 2023: Environmental and occupational lung diseases. Respirology 2024; 29:574-587. [PMID: 38826078 DOI: 10.1111/resp.14761] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Accepted: 05/16/2024] [Indexed: 06/04/2024]
Abstract
Air pollutants have various effects on human health in environmental and occupational settings. Air pollutants can be a risk factor for incidence, exacerbation/aggravation and death due to various lung diseases, including asthma, chronic obstructive pulmonary disease (COPD), hypersensitivity pneumonitis or pneumonia (HP), pulmonary fibrosis such as pneumoconiosis and malignant respiratory diseases such as lung cancer and malignant pleural mesothelioma. Environmental and occupational respiratory diseases are crucial clinical and social issues worldwide, although the burden of respiratory disease due to environmental and occupational causes varies depending on country/region, demographic variables, geographical location, industrial structure and socioeconomic situation. The correct recognition of environmental and occupational lung diseases and taking appropriate measures are essential to their effective prevention.
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Affiliation(s)
- Kazuhiro Yatera
- Department of Respiratory Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan
| | - Chinatsu Nishida
- Department of Environmental Health Engineering, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Kitakyushu, Japan
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16
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Barnes H, Elmrayed S, Barber CM, Feary J, Lee CT, Gandhi S, Peters CE, Salisbury ML, Johannson KA. Scoping review of exposure questionnaires and surveys in interstitial lung disease. BMJ Open Respir Res 2024; 11:e002155. [PMID: 38754906 PMCID: PMC11097806 DOI: 10.1136/bmjresp-2023-002155] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Accepted: 04/26/2024] [Indexed: 05/18/2024] Open
Abstract
BACKGROUND Many interstitial lung diseases (ILDs) have clear causal relationships with environmental and occupational exposures. Exposure identification can assist with diagnosis, understanding disease pathogenesis, prognostication and prevention of disease progression and occurrence in others at risk. Despite the importance of exposure identification in ILD, there is no standardised assessment approach. Many questionnaires are in clinical and research use, yet their utility, applicability, relevance and performance characteristics are unknown. OBJECTIVES This scoping review aimed to summarise the available evidence relating to ILD exposure assessment questionnaires, identify research gaps and inform the content for a future single evidence-based ILD questionnaire. METHODS A scoping review based on Arksey and O'Malley's methodological framework was conducted. ELIGIBILITY CRITERIA Any questionnaire that elicited exposures specific to ILD was included. A modified COSMIN Risk of Bias Framework was used to assess quality. SOURCES OF EVIDENCE Relevant articles were identified from MEDLINE and EMBASE up to 23 July 2023. RESULTS 22 exposure questionnaires were identified, including 15 generally pertaining to ILD, along with several disease-specific questionnaires for hypersensitivity pneumonitis (n=4), chronic beryllium disease, sarcoidosis and silicosis (1 questionnaire each). For most questionnaires, quality was low, whereby the methods used to determine exposure inclusion and questionnaire validation were not reported or not performed. Collectively the questionnaires covered 158 unique exposures and at-risk occupations, most commonly birds, mould/water damage, wood dust, asbestos, farming, automotive mechanic and miners. Only five questionnaires also provided free-text fields, and 13 queried qualifiers such as temporality or respiratory protection. CONCLUSIONS Designing a robust ILD-specific questionnaire should include an evidence-based and relevance-based approach to exposure derivation, with clinicians and patients involved in its development and tested to ensure relevance and feasibility.
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Affiliation(s)
- Hayley Barnes
- School of Translational Medicine, Monash University, Melbourne, Victoria, Australia
- Monash Centre for Occupational and Environmental Health, Monash University, Melbourne, Victoria, Australia
| | - Seham Elmrayed
- Institute of Global Health and Human Ecology, American University in Cairo, Cairo, Egypt
| | | | - Johanna Feary
- Royal Brompton Hospital, Guys and St Thomas' NHS Foundation Trust, London, UK
- National Heart and Lung Institute, Imperial College, London, UK
| | - Cathryn T Lee
- Pulmonary and Critical Care Medicine, University of Chicago, Chicago, Illinois, USA
| | - Sheiphali Gandhi
- Department of Medicine, University of California San Francisco, San Francisco, California, USA
| | - Cheryl E Peters
- Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
- BC Cancer, Vancouver, British Columbia, Canada
- School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
| | | | - Kerri A Johannson
- Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
- Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
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17
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Sunman B, Kiper N. Fibrotic lung diseases in children. Pediatr Pulmonol 2024; 59:1165-1174. [PMID: 38353393 DOI: 10.1002/ppul.26905] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Revised: 01/08/2024] [Accepted: 01/31/2024] [Indexed: 04/30/2024]
Abstract
In children, pulmonary fibrosis (PF) is an extremely unusual entity that can be observed in some types of interstitial lung disease (ILD). Defining whether ILD is accompanied by PF is important for targeted therapy. Algorithm for the diagnosis of PF in children is not clearly established. Besides, the clinical, radiological, and histological definitions commonly used to diagnose particularly the cases of idiopathic PF in adult patients, is not applicable to pediatric cases. However, a few studies conducted in children offer good exemplary diagnostic approach to fibrosing ILD. Thorax high resonance computed tomography and/or lung biopsy scanning can provide valuable information about PF. Another issue that has not been clearly established is when to start antifibrotic treatment in pediatric patients with PF. The objective of this current review is to provide a comprehensive overview of pediatric PF by drawing upon adult research, particularly focusing on the areas of uncertainty.
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Affiliation(s)
- Birce Sunman
- Department of Pediatric Pulmonology, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Nural Kiper
- Department of Pediatric Pulmonology, Hacettepe University Faculty of Medicine, Ankara, Turkey
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18
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Bhatta R, Abou-Ghaida J, Bhattarai S, Blavo C. A Case of Immunomodulator-Responsive Hypersensitivity Pneumonitis Secondary to Chronic Passive Smoke Inhalation. Cureus 2024; 16:e58723. [PMID: 38779275 PMCID: PMC11110094 DOI: 10.7759/cureus.58723] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Accepted: 04/21/2024] [Indexed: 05/25/2024] Open
Abstract
Hypersensitivity pneumonitis (HP) is a pulmonary disease characterized by inflammation and fibrosis of the lung parenchyma following chronic exposure to immunogenic antigens. The pathophysiology of HP involves type 3 and type 4 hypersensitivity reactions leading to acute and chronic manifestations, respectively. Clinically, it manifests as exertional dyspnea and wheezing. Pulmonary function tests display a pattern of restrictive lung disease, and high-resolution CT scans display a pattern of ground glass opacities, centrilobular nodules, and mosaic attenuation. Antigen avoidance remains the only method for primary prevention. Alternative therapy may be needed due to either the inability to avoid antigens or the lack of antigen identification. Prednisone 0.5 mg/kg per day is the first-line treatment for acute non-fibrotic forms of HP. In chronic or fibrotic HP, the immunomodulator mycophenolate mofetil (MMF) was shown to be an effective treatment in improving the diffusing capacity of the lungs for carbon monoxide and forced vital capacity, but not overall survival. The following study aims to bring to attention the need for additional prospective multicenter clinical trials to clarify the role of MMF as an immunomodulator in fibrosing HP.
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Affiliation(s)
- Rabi Bhatta
- Internal Medicine, Universal Health Services, Inc. (UHS) Southern California Medical Education Consortium, Temecula, USA
| | - Jaafar Abou-Ghaida
- Osteopathic Medicine, Nova Southeastern University Dr. Kiran C. Patel College of Osteopathic Medicine, Clearwater, USA
| | - Sanket Bhattarai
- Clinical and Translational Medicine, Larkin Health System, South Miami, USA
| | - Cyril Blavo
- Pediatrics, Nova Southeastern University Dr. Kiran C. Patel College of Osteopathic Medicine, Clearwater, USA
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Plut D, Winant AJ, Mahomed N, Sodhi KS, Kasznia-Brown J, Williams-Weekes T, Daltro P, Das KM, Lee EY. Unusual pediatric lung infections: imaging findings. Pediatr Radiol 2024; 54:516-529. [PMID: 38097820 PMCID: PMC10984910 DOI: 10.1007/s00247-023-05818-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Revised: 11/16/2023] [Accepted: 11/17/2023] [Indexed: 04/04/2024]
Abstract
Pediatric lung infections continue to be a leading cause of pediatric morbidity and mortality. Although both pediatric and general radiologists are familiar with typical lung infections and their imaging findings in children, relatively rare lung infections continue to present a diagnostic challenge. In addition, the advances in radiological imaging and emergence of several new lung infections in recent years facilitated the need for up-to-date knowledge on this topic. In this review article, we discuss the imaging findings of pediatric lung infections caused by unusual/uncommon and new pathogens. We review the epidemiological, clinical, and radiological imaging findings of viral (coronavirus disease 2019, Middle East respiratory syndrome, bird flu), bacterial (Streptococcus anginosus, Francisella tularensis, Chlamydia psittaci), and parasitic lung infections (echinococcosis, paragonimiasis, amoebiasis). Additional disorders whose clinical course and imaging findings may mimic lung infections in children (hypersensitivity pneumonitis, pulmonary hemorrhage, eosinophilic pneumonia) are also presented, to aid in differential diagnosis. As the clinical presentation of children with new and unusual lung infections is often non-specific, imaging evaluation plays an important role in initial detection, follow-up for disease progression, and assessment of potential complications.
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Affiliation(s)
- Domen Plut
- Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000, Ljubljana, Slovenia.
- Department of Pediatric Radiology, Clinical Radiology Institute, University Medical Centre Ljubljana, Zaloška cesta 2, 1000, Ljubljana, Slovenia.
| | - Abbey J Winant
- Department of Radiology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA
| | - Nasreen Mahomed
- Department of Radiology, University of Witwatersrand, Johannesburg, South Africa
| | - Kushaljit Singh Sodhi
- Mallinckrodt Institute of Radiology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA
- Department of Radiodiagnosis, PGIMER, Chandigarh, India
| | | | | | - Pedro Daltro
- Department of Radiology, Clínica de Diagnóstico por Imagem, Rio de Janeiro, Brazil
| | - Karuna M Das
- Department of Radiology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates
| | - Edward Y Lee
- Department of Radiology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA
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20
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Jung HI, Nam DR, You SH, Jung JW, Gu KM, Jung SY. Nationwide Study of the Epidemiology, Diagnosis, and Treatment of Hypersensitivity Pneumonitis in Korea. J Korean Med Sci 2024; 39:e96. [PMID: 38501183 PMCID: PMC10948259 DOI: 10.3346/jkms.2024.39.e96] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Accepted: 12/05/2023] [Indexed: 03/20/2024] Open
Abstract
BACKGROUND Hypersensitivity pneumonitis (HP) is a condition with an uncertain global incidence, and information on its diagnosis and management is limited. This study aimed to address these knowledge gaps. METHODS This study utilized customized claims data from the Health Insurance Review and Assessment Service (HIRA) in South Korea from January 2010, to December 2021. Patients with HP were identified based on the diagnosis code (International Classification of Diseases, 10th Revision, J67) between 2011 and 2020. Incident HP cases were defined as new HP claims, excluding those with claims in the previous year. The study examined various factors such as age, sex, comorbidities, diagnostic methods, and treatment patterns. Additionally, multivariate logistic regression analysis was performed to identify risk factors associated with treatment initiation. RESULTS A total of 8,678 HP incident cases were confirmed, with age- and sex-adjusted annual incidence rates ranging from 1.14/100,000 in 2020 to 2.16/100,000 in 2012. The mean age of patients with incident HP was 52 years, with a higher incidence observed among males. Additionally, the most common comorbidity was asthma. Bronchoscopy was performed on 16.9% of patients, and 25.4% of patients did not receive treatment within 1 year of diagnosis. Among those who received treatment, prednisone was the most used systemic steroid, and azathioprine was the most commonly used second-line immunosuppressant. Factors associated with treatment initiation included the female sex, having asthma or gastroesophageal reflux disease (GERD), and undergoing bronchoscopy. CONCLUSION This study provides valuable insights into the incidence, diagnosis, and treatment patterns of HP in South Korea using nationwide medical claims data.
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Affiliation(s)
- Hae In Jung
- Division of Pulmonary and Allergy Medicine, Department of Internal Medicine, Chung-Ang University Hospital, Seoul, Korea
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Dal Ri Nam
- College of Pharmacy, Chung-Ang University, Seoul, Korea
- Department of Global Innovative Drugs, Graduate School of Chung-Ang University, Chung-Ang University, Seoul, Korea
| | - Seung-Hun You
- College of Pharmacy, Chung-Ang University, Seoul, Korea
- Department of Global Innovative Drugs, Graduate School of Chung-Ang University, Chung-Ang University, Seoul, Korea
| | - Jae-Woo Jung
- Division of Pulmonary and Allergy Medicine, Department of Internal Medicine, Chung-Ang University Hospital, Seoul, Korea
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Kang-Mo Gu
- Division of Pulmonary and Allergy Medicine, Department of Internal Medicine, Chung-Ang University Hospital, Seoul, Korea
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea.
| | - Sun-Young Jung
- College of Pharmacy, Chung-Ang University, Seoul, Korea
- Department of Global Innovative Drugs, Graduate School of Chung-Ang University, Chung-Ang University, Seoul, Korea.
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21
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Gandhi SA, Min B, Fazio JC, Johannson KA, Steinmaus C, Reynolds CJ, Cummings KJ. The Impact of Occupational Exposures on the Risk of Idiopathic Pulmonary Fibrosis: A Systematic Review and Meta-Analysis. Ann Am Thorac Soc 2024; 21:486-498. [PMID: 38096107 PMCID: PMC10913770 DOI: 10.1513/annalsats.202305-402oc] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Accepted: 12/13/2023] [Indexed: 03/02/2024] Open
Abstract
Rationale: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic pulmonary disorder of unknown etiology that is characterized by a usual interstitial pneumonia pattern. Previous meta-analyses have reported associations between occupational exposures and IPF, but higher-quality studies have been published in recent years, doubling the number of studied patients. Objectives: To provide a contemporary and comprehensive assessment of the relationship between occupational exposures and IPF. Methods: We searched PubMed, Embase, and Web of Science through July 2023 to identify all publications on occupational exposure and IPF. We conducted a meta-analysis of the occupational burden, odds ratio (OR), and population attributable fraction (PAF) of exposures. Five exposure categories were analyzed: vapors, gas, dust, and fumes (VGDF); metal dust; wood dust; silica dust; and agricultural dust. A comprehensive bias assessment was performed. The study protocol was registered in the International Prospective Register of Systematic Reviews (identifier CRD42021267808). Results: Our search identified 23,942 publications. Sixteen publications contained relative risks needed to calculate pooled ORs and PAFs, and 12 additional publications reported an occupational burden within a case series. The proportion of cases with occupational exposures to VGDF was 44% (95% confidence interval [CI], 36-53%), with a range of 8-17% within more specific exposure categories. The pooled OR was increased for VGDF at 1.8 (95% CI, 1.3-2.4), with a pooled PAF of 21% (95% CI, 15-28%). ORs and PAFs, respectively, were found to be 1.6 and 7% for metal dust, 1.6 and 3% for wood dust, 1.8 and 14% for agricultural dust, and 1.8 and 4% for silica dust. The pooled ORs and PAFs within specific exposure categories ranged from 1.6 to 1.8 and from 4% to 14%, respectively. We identified some publication bias, but it was not sufficient to diminish the association between occupational exposures and IPF based on sensitivity analysis and bias assessment. Conclusions: Our findings indicate that 21% of IPF cases (or approximately one in five) could be prevented by removal of occupational exposure (alongside a pooled OR of 1.8). Additionally, 44% of patients with IPF report occupational exposure to VGDF. This meta-analysis suggests that a considerable number of cases of IPF are attributable to inhaled occupational exposures and warrant increased consideration in the clinical care of patients and future prevention efforts.
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Affiliation(s)
- Sheiphali A. Gandhi
- Division of Occupational, Environmental, and Climate Medicine, Department of Medicine, University of California, San Francisco, San Francisco, California
| | - Bohyung Min
- Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Jane C. Fazio
- Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, University of California, Los Angeles, Los Angeles, California
| | | | - Craig Steinmaus
- School of Public Health, University of California, Berkeley, Berkeley, California
| | - Carl J. Reynolds
- Faculty of Medicine, National Heart and Lung Institute, Imperial College of London, London, United Kingdom; and
| | - Kristin J. Cummings
- Occupational Health Branch, California Department of Public Health, Richmond, California
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22
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Casal A, Suárez-Antelo J, Riveiro V, Ferreiro L, Rodríguez-García C, de Alegría AM, Antúnez JR, Tobes ME, Otero B, Rodríguez-Núñez N, Álvarez-Dobaño JM, Vargas-Osorio K, Gude F, Valdés L. Hypersensitivity pneumonitis: application of a new diagnostic algorithm to a time series of the disease. Expert Rev Respir Med 2024; 18:237-243. [PMID: 38775489 DOI: 10.1080/17476348.2024.2358939] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Accepted: 05/20/2024] [Indexed: 05/31/2024]
Abstract
BACKGROUND The diagnostic criteria for Hypersensitivity pneumonitis (HP) have changed over time. Our aim is to apply a recent diagnostic algorithm to a historical series of patients diagnosed with HP to assess its distribution according to current diagnostic criteria and the diagnostic confidence achieved. RESEARCH DESIGN AND METHODS Application to each patient the algorithm criteria. The diagnosis was HP (≥90%), provisional high (70-89%) or low confidence (51-69%) or non-HP (unlikely) (≤50%); or HP, provisional or non-HP, if they had lung biopsy. RESULTS 129 patients [mean age 64 ± 12 years; 79 (61.2%) women] were included of which 16 (12.4%) were diagnosed on the basis of high clinical suspicion. After applying the algorithm, 106 patients (82.2%) could be evaluated and 83 (78.3%) had a diagnosis of HP or high confidence. Lung biopsy was able to establish a diagnosis of certainty in another 21 patients and a provisional diagnosis in 9 more [total, 113 (87.6%)]. The 16 patients without strict diagnostic criteria for HP had a low confidence diagnosis. A total of 56 lung biopsies (64.4%) could have been avoided according to the new guidelines. CONCLUSIONS The application of this algorithm achieves a high diagnostic yield in HP, significantly reducing the number of lung biopsies required.
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Affiliation(s)
- Ana Casal
- Pulmonology Unit, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Juan Suárez-Antelo
- Pulmonology Unit, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Vanessa Riveiro
- Pulmonology Unit, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Lucía Ferreiro
- Pulmonology Unit, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain
- Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain
| | - Carlota Rodríguez-García
- Pulmonology Unit, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | | | - José Ramón Antúnez
- Pathological Anatomy Unit, University Clinical Hospital of Santiago de Compostela, Spain
| | - María-Elena Tobes
- Pulmonology Unit, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Borja Otero
- Nursing Service, Esteve Teijin, Santiago de Compostela, Spain
| | - Nuria Rodríguez-Núñez
- Pulmonology Unit, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - José Manuel Álvarez-Dobaño
- Pulmonology Unit, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain
- Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain
| | - Kelly Vargas-Osorio
- Pathological Anatomy Unit, University Clinical Hospital of Santiago de Compostela, Spain
| | - Francisco Gude
- Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain
- Clinical Epidemiology Unit, University Clinical Hospital of Santiago de Compostela, Santiago de compostela, Spain
| | - Luis Valdés
- Pulmonology Unit, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain
- Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain
- Department of Medicine, Faculty of Medicine of the University of Santiago de Compostela, Spain
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23
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Petnak T, Cheungpasitporn W, Thongprayoon C, Sodsri T, Tangpanithandee S, Moua T. Phenotypic subtypes of fibrotic hypersensitivity pneumonitis identified by machine learning consensus clustering analysis. Respir Res 2024; 25:41. [PMID: 38238763 PMCID: PMC10797808 DOI: 10.1186/s12931-024-02664-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Accepted: 01/01/2024] [Indexed: 01/22/2024] Open
Abstract
BACKGROUND Patients with fibrotic hypersensitivity pneumonitis (f-HP) have varied clinical and radiologic presentations whose associated phenotypic outcomes have not been previously described. We conducted a study to evaluate mortality and lung transplant (LT) outcomes among clinical clusters of f-HP as characterized by an unsupervised machine learning approach. METHODS Consensus cluster analysis was performed on a retrospective cohort of f-HP patients diagnosed according to recent international guideline. Demographics, antigen exposure, radiologic, histopathologic, and pulmonary function findings along with comorbidities were included in the cluster analysis. Cox proportional-hazards regression was used to assess mortality or LT risk as a combined outcome for each cluster. RESULTS Three distinct clusters were identified among 336 f-HP patients. Cluster 1 (n = 158, 47%) was characterized by mild restriction on pulmonary function testing (PFT). Cluster 2 (n = 46, 14%) was characterized by younger age, lower BMI, and a higher proportion of identifiable causative antigens with baseline obstructive physiology. Cluster 3 (n = 132, 39%) was characterized by moderate to severe restriction. When compared to cluster 1, mortality or LT risk was lower in cluster 2 (hazard ratio (HR) of 0.42; 95% CI, 0.21-0.82; P = 0.01) and higher in cluster 3 (HR of 1.76; 95% CI, 1.24-2.48; P = 0.001). CONCLUSIONS Three distinct phenotypes of f-HP with unique mortality or transplant outcomes were found using unsupervised cluster analysis, highlighting improved mortality in fibrotic patients with obstructive physiology and identifiable antigens.
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Affiliation(s)
- Tananchai Petnak
- Division of Pulmonary and Pulmonary Critical Care Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Nakhon Pathom, Thailand
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, 200 First St SW, Rochester, MN, 55905, United States
| | | | - Charat Thongprayoon
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, United States
| | - Tulaton Sodsri
- Faculty of Medicine Ramathibodi Hospital, Chakri Naruebodindra Medical Institute, Mahidol University, Samut Prakan, Thailand
| | | | - Teng Moua
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, 200 First St SW, Rochester, MN, 55905, United States.
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24
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Calaras D, David A, Vasarmidi E, Antoniou K, Corlateanu A. Hypersensitivity Pneumonitis: Challenges of a Complex Disease. Can Respir J 2024; 2024:4919951. [PMID: 38283656 PMCID: PMC10810695 DOI: 10.1155/2024/4919951] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Revised: 11/19/2023] [Accepted: 12/29/2023] [Indexed: 01/30/2024] Open
Abstract
Hypersensitivity pneumonitis (HP) is a complex interstitial lung disease caused by chronic inhalation of a wide variety of antigens in susceptible and sensitized individuals, commonly associated with an occupational exposure. An impressive number of inciting antigens causing hypersensitivity pneumonitis have been found to cover a wide range of occupations. As working practices have changed over time, especially in industrialized countries, new names for occupational HP have emerged. This review emphasizes the main diagnostic issues arising from the high variability of clinical presentation and the broad spectrum of causal antigens. Furthermore, it provides an overview of current methods to unveil possible causes of hypersensitivity pneumonitis, highlights HP's current diagnostic and treatment challenges and the remaining areas of uncertainty, and presents prevention strategies.
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Affiliation(s)
- Diana Calaras
- Department of Pulmonology and Allergology, State University of Medicine and Pharmacy “Nicolae Testemitanu”, Chisinau, Moldova
| | - Aliona David
- Outpatient Department, Institute of Phtisiopneumology “Chiril Draganiuc”, Chisinau, Moldova
| | - Eirini Vasarmidi
- Department of Respiratory Medicine, Laboratory of Molecular and Cellular Pulmonology, School of Medicine, University of Crete, Heraklion, Greece
| | - Katerina Antoniou
- Department of Respiratory Medicine, Laboratory of Molecular and Cellular Pulmonology, School of Medicine, University of Crete, Heraklion, Greece
| | - Alexandru Corlateanu
- Department of Pulmonology and Allergology, State University of Medicine and Pharmacy “Nicolae Testemitanu”, Chisinau, Moldova
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25
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Samsonova MV, Chernyaev AL. [Morphology of hypersensitivity pneumonitis]. Arkh Patol 2024; 86:67-73. [PMID: 38881008 DOI: 10.17116/patol20248603167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/18/2024]
Abstract
Hypersensitivity pneumonitis (HP) is one of the most common interstitial lung diseases, the manifestations of which are diverse, and the diagnosis is complex and requires a multidisciplinary approach. HP is an immunologically determined disease in response to inhaled antigens. The main feature of the disease is terminal bronchiole's involvement accompanied by interstitial inflammation and/or fibrosis together with the presence of non-necrotizing granulomas in the interalveolar septa and bronchioles. The article presents the histological features of non-fibrous and fibrotic variants of the disease. Well-defined diagnostic criteria were formulated on the basis of published international recommendations and the authors' own experience.
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Affiliation(s)
- M V Samsonova
- Pulmonology Scientific Research Institute, Moscow, Russia
- Moscow Technological Scientific Center named after A.S. Loginov, Moscow, Russia
| | - A L Chernyaev
- Pulmonology Scientific Research Institute, Moscow, Russia
- Avtsyn Research Institute of Human Morphology of Petrovsky National Research Centre of Surgery, Moscow, Russia
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26
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Amin R, Pandey R, Vaishali K, Acharya V, Sinha MK, Kumar N. Therapeutic Approaches for the Treatment of Interstitial Lung Disease: An Exploratory Review on Molecular Mechanisms. Mini Rev Med Chem 2024; 24:618-633. [PMID: 37587813 DOI: 10.2174/1389557523666230816090112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Revised: 05/04/2023] [Accepted: 06/09/2023] [Indexed: 08/18/2023]
Abstract
BACKGROUND Interstitial Lung Diseases (ILDs) are characterized by shortness of breath caused by alveolar wall inflammation and/or fibrosis. OBJECTIVE Our review aims to study the depth of various variants of ILD, diagnostic procedures, pathophysiology, molecular dysfunction and regulation, subject and objective assessment techniques, pharmacological intervention, exercise training and various modes of delivery for rehabilitation. METHOD Articles are reviewed from PubMed and Scopus and search engines. RESULTS ILD is a rapidly progressing disease with a high mortality rate. Each variant has its own set of causal agents and expression patterns. Patients often find it challenging to self-manage due to persistent symptoms and a rapid rate of worsening. The present review elaborated on the pathophysiology, risk factors, molecular mechanisms, diagnostics, and therapeutic approaches for ILD will guide future requirements in the quest for innovative and tailored ILD therapies at the molecular and cellular levels. CONCLUSION The review highlights the rationale for conventional and novel therapeutic approaches for better management of ILD.
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Affiliation(s)
- Revati Amin
- Department of Physiotherapy, Manipal College of Health Professions, Manipal Academy of Higher Education, Manipal, India
| | - Ruchi Pandey
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hajipur, Bihar, 844102, India
| | - K Vaishali
- Department of Physiotherapy, Manipal College of Health Professions, Manipal Academy of Higher Education, Manipal, India
| | - Vishak Acharya
- Department of Pulmonary Medicine, Kasturba Medical College, Manipal Academy of Higher Education, Mangalore, India
| | - Mukesh Kumar Sinha
- Department of Physiotherapy, Manipal College of Health Professions, Manipal Academy of Higher Education, Manipal, India
| | - Nitesh Kumar
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hajipur, Bihar, 844102, India
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27
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Tomioka H, Miyazaki Y, Inoue Y, Egashira R, Kawamura T, Sano H, Johkoh T, Takemura T, Hisada T, Fukuoka J. Japanese clinical practice guide 2022 for hypersensitivity pneumonitis. Respir Investig 2024; 62:16-43. [PMID: 37931427 DOI: 10.1016/j.resinv.2023.07.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Revised: 06/23/2023] [Accepted: 07/17/2023] [Indexed: 11/08/2023]
Abstract
Considering recently published two guidelines for the diagnosis of hypersensitivity pneumonitis (HP), the Japanese Respiratory Society (JRS) has now published its own Japanese clinical practice guide for HP. Major types of HP in Japan include summer-type, home-related, bird-related, farmer's lung, painter's lung, humidifier lung, and mushroom grower's lung. Identifying causative antigens is critical for increasing diagnostic confidence, as well as improving prognosis through appropriate antigen avoidance. This guide proposes a comprehensive antigen questionnaire including the outbreak sources reported in Japan. Drawing on the 2021 CHEST guideline, this guide highlights the antigen identification confidence level and adaptations for environmental surveys. The detection of specific antibodies against causative antigens is an important diagnostic predictor of HP. In Japan, the assessments of bird-specific IgG (pigeons, budgerigars) and the Trichosporon asahii antibody are covered by medical insurance. Although this guide adopts the 2020 ATS/JRS/ALAT guideline diagnostic criteria based on the combination of imaging findings, exposure assessment, bronchoalveolar lavage lymphocytosis, and histopathological findings, it added some annotations to facilitate the interpretation of the content and correlate the medical situation in Japan. It recommends checking biomarkers; seasonal changes in the KL-6 concentration (increase in winter for bird-related HP/humidifier lung and in summer for summer-type HP) and high KL-6 concentrations providing a basis for the suspicion of HP. Antigen avoidance is critical for disease management of HP. This guide also addresses the pharmacological management of HP, highlighting the treatment strategy for fibrotic HP including combination therapies with anti-inflammatory/immunosuppressive and antifibrotic drugs.
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Affiliation(s)
- Hiromi Tomioka
- Department of Respiratory Medicine, Kobe City Medical Center West Hospital, Kobe, Japan.
| | - Yasunari Miyazaki
- Department of Respiratory Medicine, Tokyo Medical and Dental University, Tokyo, Japan
| | - Yoshikazu Inoue
- Clinical Research Center, National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka, Japan
| | - Ryoko Egashira
- Department of Radiology, Faculty of Medicine, Saga University, Saga, Japan
| | - Tetsuji Kawamura
- National Hospital Organization Himeji Medical Center, Himeji, Japan
| | - Hiroyuki Sano
- Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Takeshi Johkoh
- Department of Radiology, Kansai Rosai Hospital, Amagasaki, Japan
| | - Tamiko Takemura
- Department of Pathology, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan
| | - Takeshi Hisada
- Gunma University Graduate School of Health Sciences, Maebashi, Japan
| | - Junya Fukuoka
- Department of Pathology Informatics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
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28
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Miseviciene V, Liakaite G, Vaidelys L, Zaveckiene J. Masks of hypersensitivity pneumonitis in children. ARCHIVES OF ENVIRONMENTAL & OCCUPATIONAL HEALTH 2023; 78:435-441. [PMID: 37861308 DOI: 10.1080/19338244.2023.2270913] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Accepted: 10/10/2023] [Indexed: 10/21/2023]
Abstract
Hypersensitivity pneumonitis (HP), also known as extrinsic allergic alveolitis, is the most common interstitial lung disease in children, but remains rarely recognized in the pediatric population. Early recognition of triggering factors and a high index of suspicion of HP could lead to timely diagnosis and individualized treatment. This study aimed to present four clinical cases of HP reported between 2012 and 2022 in Lithuania to improve the suspicion of the disease in children.
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Affiliation(s)
- Valdone Miseviciene
- Medical Academy, Pediatric Department, The Center of Pediatric Chronic Respiratory Diseases, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Gintare Liakaite
- Medical Academy, Pediatric Department, The Center of Pediatric Chronic Respiratory Diseases, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Lukas Vaidelys
- Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Jurgita Zaveckiene
- Medical Academy, Department of Radiology, Lithuanian University of Health Sciences, Kaunas, Lithuania
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29
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Chen X, Yang X, Ren Y, Xie B, Xie S, Zhao L, Wang S, Geng J, Jiang D, Luo S, He J, Shu S, Hu Y, Zhu L, Li Z, Zhang X, Liu M, Dai H. Clinical characteristics of hypersensitivity pneumonitis: non-fibrotic and fibrotic subtypes. Chin Med J (Engl) 2023; 136:2839-2846. [PMID: 37464421 PMCID: PMC10686610 DOI: 10.1097/cm9.0000000000002613] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Indexed: 07/20/2023] Open
Abstract
BACKGROUND The presence of fibrosis is a criterion for subtype classification in the newly updated hypersensitivity pneumonitis (HP) guidelines. The present study aimed to summarize differences in clinical characteristics and prognosis of non-fibrotic hypersensitivity pneumonitis (NFHP) and fibrotic hypersensitivity pneumonitis (FHP) and explore factors associated with the presence of fibrosis. METHODS In this prospective cohort study, patients diagnosed with HP through a multidisciplinary discussion were enrolled. Collected data included demographic and clinical characteristics, laboratory findings, and radiologic and histopathological features. Logistic regression analyses were performed to explore factors related to the presence of fibrosis. RESULTS A total of 202 patients with HP were enrolled, including 87 (43.1%) NFHP patients and 115 (56.9%) FHP patients. Patients with FHP were older and more frequently presented with dyspnea, crackles, and digital clubbing than patients with NFHP. Serum levels of carcinoembryonic antigen, carbohydrate antigen 125, carbohydrate antigen 153, gastrin-releasing peptide precursor, squamous cell carcinoma antigen, and antigen cytokeratin 21-1, and count of bronchoalveolar lavage (BAL) eosinophils were higher in the FHP group than in the NFHP group. BAL lymphocytosis was present in both groups, but less pronounced in the FHP group. Multivariable regression analyses revealed that older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors for the development of FHP. Twelve patients developed adverse outcomes, with a median survival time of 12.5 months, all of whom had FHP. CONCLUSIONS Older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors associated with the development of FHP. Prognosis of patients with NFHP was better than that of patients with FHP. These results may provide insights into the mechanisms of fibrosis in HP.
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Affiliation(s)
- Xueying Chen
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100029, China
| | - Xiaoyan Yang
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Capital Medical University, Beijing 100029, China
| | - Yanhong Ren
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100029, China
| | - Bingbing Xie
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100029, China
| | - Sheng Xie
- Department of Radiology, China-Japan Friendship Hospital, Beijing 100029, China
| | - Ling Zhao
- Department of Pathology, China-Japan Friendship Hospital, Beijing 100029, China
| | - Shiyao Wang
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100029, China
| | - Jing Geng
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100029, China
| | - Dingyuan Jiang
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100029, China
| | - Sa Luo
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100029, China
| | - Jiarui He
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100029, China
| | - Shi Shu
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100029, China
| | - Yinan Hu
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100029, China
| | - Lili Zhu
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100029, China
| | - Zhen Li
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100029, China
| | - Xinran Zhang
- Institute of Clinical Medical Sciences, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing 100029, China
| | - Min Liu
- Department of Radiology, China-Japan Friendship Hospital, Beijing 100029, China
| | - Huaping Dai
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100029, China
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Freitas C, Lima B, Melo N, Mota P, Novais-Bastos H, Alves H, Sokhatska O, Delgado L, Morais A. Distinct TNF-alpha and HLA polymorphisms associate with fibrotic and non-fibrotic subtypes of hypersensitivity pneumonitis. Pulmonology 2023; 29 Suppl 4:S63-S69. [PMID: 34629327 DOI: 10.1016/j.pulmoe.2021.08.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Revised: 08/01/2021] [Accepted: 08/02/2021] [Indexed: 10/20/2022] Open
Abstract
INTRODUCTION Since Hypersensitivity Pneumonitis (HP) categorization in fibrotic and nonfibrotic/inflammatory types seems to be more consistent with the distinctive clinical course and outcomes, recent international guidelines recommended the use of this classification. Moreover, fibrotic subtype may share immunogenetic and pathophysiological mechanisms with other fibrotic lung diseases. AIM To investigate HLA -A, -B, -DRB1 and TNF-α -308 gene polymorphisms among fibrotic and nonfibrotic HP patients due to avian exposure, also in comparison with asymptomatic exposed controls. METHODS We prospectively enrolled 40 HP patients, classified as fibrotic or nonfibrotic/inflammatory, and 70 exposed controls. HLA and TNF-α polymorphisms were determined by polymerase chain reaction-sequence specific primer amplification. RESULTS While HLA alleles were not associated to HP susceptibility, fibrotic HP patients showed increased frequencies of HLA A*02 (46.7% vs 25.7%; OR=2.53, p = 0.02) and HLA DRB1*14 (10.0% vs 0.7%; OR=15.44, p=0.02) alleles when compared with exposed controls, although not statistically significant after correction for multiple comparisons. TNF-α G/G genotype (associated with low TNF-α production) frequencies were significantly increased among the non-fibrotic/inflammatory HP patients comparatively to fibrotic presentations (88% vs 60%; RR=0.44; p=0.04) and controls (88% vs 63%, OR 4.33, p=0.037). Also, these patients had a significantly increased frequency of the G allele (94.0% vs 73.3%, RR=0.44, p=0.01), while fibrotic HP patients predominantly presented the A allele (26.7% vs 6.0%, RR=2.28, p=0.01). CONCLUSIONS Our results support the hypothesis that fibrotic and non-fibrotic HP subtypes exhibit a distinct profile of TNF-α and HLA polymorphisms, which may be relevant to predict disease course and better define treatment strategies.
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Affiliation(s)
- C Freitas
- Pulmonology Department, Centro Hospitalar e Universitário de São João, Porto, Portugal; Department of Medicine, Faculty of Medicine, University of Porto, Portugal.
| | - B Lima
- Oficina de Bioestatística, Ermesinde, Portugal
| | - N Melo
- Pulmonology Department, Centro Hospitalar e Universitário de São João, Porto, Portugal
| | - P Mota
- Pulmonology Department, Centro Hospitalar e Universitário de São João, Porto, Portugal; Department of Medicine, Faculty of Medicine, University of Porto, Portugal
| | - H Novais-Bastos
- Pulmonology Department, Centro Hospitalar e Universitário de São João, Porto, Portugal; Department of Medicine, Faculty of Medicine, University of Porto, Portugal; Institute for Research and Innovation in Health (I3S), University of Porto, Portugal
| | - H Alves
- National Health Institute Doutor Ricardo Jorge, Porto, Portugal
| | - O Sokhatska
- Basic and Clinical Immunology, Department of Pathology, and Center for Health Technology and Services Research (CINTESIS@RISE), Faculty of Medicine, University of Porto, Portugal
| | - L Delgado
- Basic and Clinical Immunology, Department of Pathology, and Center for Health Technology and Services Research (CINTESIS@RISE), Faculty of Medicine, University of Porto, Portugal
| | - A Morais
- Pulmonology Department, Centro Hospitalar e Universitário de São João, Porto, Portugal; Department of Medicine, Faculty of Medicine, University of Porto, Portugal
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Sánchez-Díez S, Muñoz X, Montalvo T, Ojanguren I, Romero-Mesones C, Senar JC, Peracho-Tobeña V, Cruz MJ. Sensitization to avian and fungal proteins in different work environments. ALLERGY, ASTHMA, AND CLINICAL IMMUNOLOGY : OFFICIAL JOURNAL OF THE CANADIAN SOCIETY OF ALLERGY AND CLINICAL IMMUNOLOGY 2023; 19:96. [PMID: 37957771 PMCID: PMC10644561 DOI: 10.1186/s13223-023-00852-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Accepted: 10/25/2023] [Indexed: 11/15/2023]
Abstract
INTRODUCTION Hypersensitivity pneumonitis (HP) is usually caused by the inhalation of avian and fungal proteins. The present study assesses a cohort of Urban Pest Surveillance and Control Service (UPSCS) workers with high exposure to avian and fungal antigens, in order to identify their degree of sensitization and the potential risk of developing HP. METHODS Workers were divided according to their work activity into Nest pruners (Group 1) and Others (Group 2). All individuals underwent a medical interview, pulmonary function tests and the determination of specific IgG antibodies. Antigenic proteins of pigeon sera were analysed using two-dimensional immunoblotting. Proteins of interest were sequenced by liquid-chromatography-mass spectrometry (LC-MS). RESULTS 101 workers were recruited (76 men, average age: 42 yrs); (Group 1 = 41, Group 2 = 60). Up to 30% of the study population exhibited increased levels of IgGs to pigeon, small parrot and parrot, and up to 60% showed high levels of Aspergillus and Penicillium IgGs. In Group 1, specific parakeet and Mucor IgGs were higher (p = 0.044 and 0.003 respectively) while DLCO/VA% were lower (p = 0.008) than in Group 2. Two-dimensional immunoblotting showed protein bands of 20-30 KDa recognized by HP patients but not by workers. LC-MS analysis identified Ig Lambda chain and Apolipoprotein A-I as candidate proteins for distinguishing HP patients from exposed workers. CONCLUSIONS Two pigeon proteins were identified that may play a role in the development of pathological differences between HP patients and exposed workers. DLCO/VA may have a predictive value in the development of HP disease.
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Affiliation(s)
- Silvia Sánchez-Díez
- Servicio de Neumología, Departamento de Medicina, Hospital Universitario Vall d'Hebron, Universidad Autónoma de Barcelona, Passeig Vall d'Hebron, 119, 08035, Barcelona, Spain
| | - Xavier Muñoz
- Servicio de Neumología, Departamento de Medicina, Hospital Universitario Vall d'Hebron, Universidad Autónoma de Barcelona, Passeig Vall d'Hebron, 119, 08035, Barcelona, Spain.
- CIBER Enfermedades Respiratorias (Ciberes), Madrid, Spain.
| | - Tomás Montalvo
- Servicio de Vigilancia y Control de Plagas Urbanas Agencia de Salud Pública de Barcelona, Barcelona, Spain
- CIBER de Epidemiología y Salud Pública (Ciberesp), Madrid, Spain
| | - Iñigo Ojanguren
- Servicio de Neumología, Departamento de Medicina, Hospital Universitario Vall d'Hebron, Universidad Autónoma de Barcelona, Passeig Vall d'Hebron, 119, 08035, Barcelona, Spain
- CIBER Enfermedades Respiratorias (Ciberes), Madrid, Spain
| | - Christian Romero-Mesones
- Servicio de Neumología, Departamento de Medicina, Hospital Universitario Vall d'Hebron, Universidad Autónoma de Barcelona, Passeig Vall d'Hebron, 119, 08035, Barcelona, Spain
| | - Juan Carlos Senar
- Departamento de Ecología Evolutiva y de la Conducta, Museo de Ciencias Naturales de Barcelona, Barcelona, Spain
| | - Victor Peracho-Tobeña
- Servicio de Vigilancia y Control de Plagas Urbanas Agencia de Salud Pública de Barcelona, Barcelona, Spain
| | - María-Jesús Cruz
- Servicio de Neumología, Departamento de Medicina, Hospital Universitario Vall d'Hebron, Universidad Autónoma de Barcelona, Passeig Vall d'Hebron, 119, 08035, Barcelona, Spain
- CIBER Enfermedades Respiratorias (Ciberes), Madrid, Spain
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Grewal US, Pande A. Rituximab Rescue in Treatment Refractory Hypersensitivity Pneumonitis. Am J Ther 2023; 30:e576-e578. [PMID: 35421011 DOI: 10.1097/mjt.0000000000001510] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Affiliation(s)
- Udhayvir Singh Grewal
- Department of Internal Medicine, Louisiana State University Health Sciences Center, Shreveport, LA
| | - Aman Pande
- Respiratory Institute, Cleveland Clinic Foundation, Cleveland, OH
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Kurian GK, Simonin V, Colombé J, Duplain H. Recurrent episodes of febrile dyspnoea: hypersensitivity pneumonitis caused by a household ultrasonic humidifier. BMJ Case Rep 2023; 16:e255445. [PMID: 37751984 PMCID: PMC10533670 DOI: 10.1136/bcr-2023-255445] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/30/2023] Open
Abstract
Hypersensitivity pneumonitis is an immune-mediated interstitial lung disease that presents with respiratory symptoms, with or without systemic symptoms, following exposure to an identified or unidentified external factor. It can be caused by extrinsic factors including household items such as ultrasonic humidifiers.We present an intriguing case of a previously healthy 50-year-old man who displayed recurrent episodes of progressive dyspnoea and fever after repeated exposure to his household ultrasonic humidifier. He was treated with corticosteroids, followed by the removal of the humidifier, resulting in total recovery and absence of recurrence of further episodes.The clinical presentation of hypersensitivity pneumonitis can be dramatic, and the differential diagnosis is broad. The correct diagnosis is achieved by combining clinical, radiological and histopathological patterns. The key to finding the aetiology lies in a thorough history, with an important role for household investigations to identify the external factor.
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Affiliation(s)
| | | | | | - Hervé Duplain
- Internal Medicine, Hôpital du Jura, Delémont, Switzerland
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Lewandowska KB, Szturmowicz M, Lechowicz U, Franczuk M, Błasińska K, Falis M, Błaszczyk K, Sobiecka M, Wyrostkiewicz D, Siemion-Szcześniak I, Bartosiewicz M, Radwan-Röhrenschef P, Roży A, Chorostowska-Wynimko J, Tomkowski WZ. The Presence of T Allele (rs35705950) of the MUC5B Gene Predicts Lower Baseline Forced Vital Capacity and Its Subsequent Decline in Patients with Hypersensitivity Pneumonitis. Int J Mol Sci 2023; 24:10748. [PMID: 37445925 PMCID: PMC10341926 DOI: 10.3390/ijms241310748] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Revised: 06/24/2023] [Accepted: 06/26/2023] [Indexed: 07/15/2023] Open
Abstract
Hypersensitivity pneumonitis (HP) is an exposure-related interstitial lung disease with two phenotypes-fibrotic and non-fibrotic. Genetic predisposition is an important factor in the disease pathogenesis and fibrosis development. Several genes are supposed to be associated with the fibrosing cascade in the lungs. One of the best-recognized and most prevalent is the common MUC5B gene promoter region polymorphism variant rs35705950. The aim of our study was to establish the frequency of the minor allele of the MUC5B gene in the population of patients with HP and to find the relationship between the MUC5B promoter region polymorphism and the development of lung fibrosis, the severity of the disease course, and the response to the treatment in patients with HP. Eighty-six consecutive patients with HP were tested for the genetic variant rs35705950 of the MUC-5B gene. Demographic, radiological, and functional parameters were collected. The relationship between the presence of the T allele and lung fibrosis, pulmonary function test parameters, and the treatment response were analyzed. The minor allele frequency in the study group was 17%, with the distribution of the genotypes GG in 69.8% of subjects and GT/TT in 30.2%. Patients with the GT/TT phenotype had significantly lower baseline forced vital capacity (FVC) and significantly more frequently had a decline in FVC with time. The prevalence of lung fibrosis in high-resolution computed tomography (HRCT) was not significantly increased in GT/TT variant carriers compared to GG ones. The patients with the T allele tended to respond worse to immunomodulatory treatment and more frequently received antifibrotic drugs. In conclusions: The frequency of MUC5B polymorphism in HP patients is high. The T allele may indicate a worse disease course, worse immunomodulatory treatment response, and earlier need for antifibrotic treatment.
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Affiliation(s)
- Katarzyna B. Lewandowska
- 1st Department of Lung Diseases, National Research Institute of Tuberculosis and Lung Diseases, Płocka 26, 01-138 Warsaw, Poland; (M.S.)
| | - Monika Szturmowicz
- 1st Department of Lung Diseases, National Research Institute of Tuberculosis and Lung Diseases, Płocka 26, 01-138 Warsaw, Poland; (M.S.)
| | - Urszula Lechowicz
- Department of Genetics and Clinical Immunology, National Research Institute of Tuberculosis and Lung Diseases, Płocka 26, 01-138 Warsaw, Poland; (U.L.)
| | - Monika Franczuk
- Department of Respiratory Physiopathology, National Research Institute of Tuberculosis and Lung Diseases, Płocka 26, 01-138 Warsaw, Poland;
| | - Katarzyna Błasińska
- Department of Radiology, National Research Institute of Tuberculosis and Lung Diseases, Płocka 26, 01-138 Warsaw, Poland
| | - Maria Falis
- 1st Department of Lung Diseases, National Research Institute of Tuberculosis and Lung Diseases, Płocka 26, 01-138 Warsaw, Poland; (M.S.)
| | - Kamila Błaszczyk
- 1st Department of Lung Diseases, National Research Institute of Tuberculosis and Lung Diseases, Płocka 26, 01-138 Warsaw, Poland; (M.S.)
| | - Małgorzata Sobiecka
- 1st Department of Lung Diseases, National Research Institute of Tuberculosis and Lung Diseases, Płocka 26, 01-138 Warsaw, Poland; (M.S.)
| | - Dorota Wyrostkiewicz
- 1st Department of Lung Diseases, National Research Institute of Tuberculosis and Lung Diseases, Płocka 26, 01-138 Warsaw, Poland; (M.S.)
| | - Izabela Siemion-Szcześniak
- 1st Department of Lung Diseases, National Research Institute of Tuberculosis and Lung Diseases, Płocka 26, 01-138 Warsaw, Poland; (M.S.)
| | - Małgorzata Bartosiewicz
- 1st Department of Lung Diseases, National Research Institute of Tuberculosis and Lung Diseases, Płocka 26, 01-138 Warsaw, Poland; (M.S.)
| | - Piotr Radwan-Röhrenschef
- 1st Department of Lung Diseases, National Research Institute of Tuberculosis and Lung Diseases, Płocka 26, 01-138 Warsaw, Poland; (M.S.)
| | - Adriana Roży
- Department of Genetics and Clinical Immunology, National Research Institute of Tuberculosis and Lung Diseases, Płocka 26, 01-138 Warsaw, Poland; (U.L.)
| | - Joanna Chorostowska-Wynimko
- Department of Genetics and Clinical Immunology, National Research Institute of Tuberculosis and Lung Diseases, Płocka 26, 01-138 Warsaw, Poland; (U.L.)
| | - Witold Z. Tomkowski
- 1st Department of Lung Diseases, National Research Institute of Tuberculosis and Lung Diseases, Płocka 26, 01-138 Warsaw, Poland; (M.S.)
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Luke ND, Vefali B, Chow P, Miller R. Acute Recreational Cannabis-Induced Hypersensitivity Pneumonitis: A Case Report. Cureus 2023; 15:e37312. [PMID: 37181992 PMCID: PMC10166773 DOI: 10.7759/cureus.37312] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/08/2023] [Indexed: 05/16/2023] Open
Abstract
Hypersensitivity pneumonitis (HP) is a lung disease in which foreign matter is inhaled and exposed to lung parenchymal and interstitial tissue. Such matter may include pollen, molds, chemicals, and smoke. HP leads to widespread inflammation and even fibrosis in chronic forms; the main route of treatment usually involves corticosteroids and antifibrotics as needed. We describe a patient case in which HP was diagnosed after using recreational marijuana, and her chest x-ray had a complete resolution after one day of a corticosteroid regimen. As recreational marijuana use increases, clinicians need to keep HP on the differential diagnosis in patients that frequently utilize recreational marijuana obtained through illicit business.
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Affiliation(s)
- Nicholas D Luke
- Emergency Department, St. Barnabas Hospital Health System, The Bronx, USA
| | - Baris Vefali
- Internal Medicine, Saint Michael's Medical Center, Newark, USA
| | - Priscilla Chow
- Pulmonology and Critical Care, Saint Michael's Medical Center, Newark, USA
| | - Richard Miller
- Pulmonology and Critical Care, Saint Michael's Medical Center, Newark, USA
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Bronchoalveolar Lavage Cell Count and Lymphocytosis Are the Important Discriminators between Fibrotic Hypersensitivity Pneumonitis and Idiopathic Pulmonary Fibrosis. Diagnostics (Basel) 2023; 13:diagnostics13050935. [PMID: 36900078 PMCID: PMC10000588 DOI: 10.3390/diagnostics13050935] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 02/21/2023] [Accepted: 02/27/2023] [Indexed: 03/06/2023] Open
Abstract
BACKGROUND Fibrotic hypersensitivity pneumonitis (fHP) shares many features with other fibrotic interstitial lung diseases (ILD), and as a result it can be misdiagnosed as idiopathic pulmonary fibrosis (IPF). We aimed to determine the value of bronchoalveolar lavage (BAL) total cell count (TCC) and lymphocytosis in distinguishing fHP and IPF and to evaluate the best cut-off points discriminating these two fibrotic ILD. METHODS A retrospective cohort study of fHP and IPF patients diagnosed between 2005 and 2018 was conducted. Logistic regression was used to evaluate the diagnostic utility of clinical parameters in differentiating between fHP and IPF. Based on the ROC analysis, BAL parameters were evaluated for their diagnostic performance, and optimal diagnostic cut-offs were established. RESULTS A total of 136 patients (65 fHP and 71 IPF) were included (mean age 54.97 ± 10.87 vs. 64.00 ± 7.18 years, respectively). BAL TCC and the percentage of lymphocytes were significantly higher in fHP compared to IPF (p < 0.001). BAL lymphocytosis >30% was found in 60% of fHP patients and none of the patients with IPF. The logistic regression revealed that younger age, never smoker status, identified exposure, lower FEV1, higher BAL TCC and higher BAL lymphocytosis increased the probability of fibrotic HP diagnosis. The lymphocytosis >20% increased by 25 times the odds of fibrotic HP diagnosis. The optimal cut-off values to differentiate fibrotic HP from IPF were 15 × 106 for TCC and 21% for BAL lymphocytosis with AUC 0.69 and 0.84, respectively. CONCLUSIONS Increased cellularity and lymphocytosis in BAL persist despite lung fibrosis in HP patients and may be used as important discriminators between IPF and fHP.
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Database analysis of hypersensitivity pneumonitis in Japan. Respir Investig 2023; 61:172-180. [PMID: 36696702 DOI: 10.1016/j.resinv.2022.12.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 11/17/2022] [Accepted: 12/08/2022] [Indexed: 01/24/2023]
Abstract
BACKGROUND Three epidemiological small-scale studies on hypersensitivity pneumonitis (HP) have been performed in Japan to date. Herein, we aimed to clarify the clinical characteristics of various types of HP diseases using a large nationwide database in Japan. METHODS We used the Japanese Diagnostic Procedure Combination database that includes data from 1,031 participant hospitals. Patients with HP from 2011 to 2017 were identified using International Classification of Diseases 10th Revision codes. We analyzed patient characteristics, the yearly transition of the number of HP cases, rate per one million hospitalizations, geographical distribution, seasonality, and risk factors for in-hospital mortality. RESULTS In total, 3,634 patients with HP were identified, including summer-type HP (SHP) (n = 490), bird fancier's lung (BFL) (n = 199), ventilation pneumonitis (n = 106), farmer's lung (n = 48), and unspecified HP (n = 2761). The length of hospital stay was significantly longer in patients with BFL (19 days) than in patients with SHP (15 days). SHP was more prevalent in the southwestern region of Japan, and hospitalization occurred mainly in summer (37.8%) and fall (37.3%). Ventilation pneumonitis was predominant in winter (28.6%) and spring (38.7%). In-hospital mortality was significantly associated with old age (p < 0.001), low body mass index (p = 0.016), severe dyspnea (p < 0.001), and BFL diagnosis on admission (p = 0.031). CONCLUSIONS This study revealed the clinical characteristics of SHP and BFL, including the frequency of causative antigens, geographical distribution, seasonality, and risk factors for mortality, which may help in diagnosing HP and identifying causative antigens.
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Diagnosis of Fibrotic Hypersensitivity Pneumonitis: Is There a Role for Biomarkers? Life (Basel) 2023; 13:life13020565. [PMID: 36836922 PMCID: PMC9966605 DOI: 10.3390/life13020565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2022] [Revised: 01/31/2023] [Accepted: 02/03/2023] [Indexed: 02/19/2023] Open
Abstract
Hypersensitivity pneumonitis is a complex interstitial lung syndrome and is associated with significant morbimortality, particularly for fibrotic disease. This condition is characterized by sensitization to a specific antigen, whose early identification is associated with improved outcomes. Biomarkers measure objectively biologic processes and may support clinical decisions. These tools evolved to play a crucial role in the diagnosis and management of a wide range of human diseases. This is not the case, however, with hypersensitivity pneumonitis, where there is still great room for research in the path to find consensual diagnostic biomarkers. Gaps in the current evidence include lack of validation, validation against healthy controls alone, small sampling and heterogeneity in diagnostic and classification criteria. Furthermore, discriminatory accuracy is currently limited by overlapping mechanisms of inflammation, damage and fibrogenesis between ILDs. Still, biomarkers such as BAL lymphocyte counts and specific serum IgGs made their way into clinical guidelines, while others including KL-6, SP-D, YKL-40 and apolipoproteins have shown promising results in leading centers and have potential to translate into daily practice. As research proceeds, it is expected that the emergence of novel categories of biomarkers will offer new and thriving tools that could complement those currently available.
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Li Y, Lian Z, Li Q, Ding W, Wang W, Zhang L, Muhataer X, Zhou Y, Yang X, Wu C. Molecular mechanism by which the Notch signaling pathway regulates autophagy in a rat model of pulmonary fibrosis in pigeon breeder's lung. Open Med (Wars) 2023; 18:20230629. [PMID: 36785767 PMCID: PMC9921914 DOI: 10.1515/med-2023-0629] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Revised: 11/17/2022] [Accepted: 12/09/2022] [Indexed: 02/11/2023] Open
Abstract
This study investigated the molecular mechanisms underlying the involvement of the Notch signaling pathway and autophagy in the development of pulmonary fibrosis in pigeon breeder's lung (PBL). Rats were divided into control (Ctrl), PBL model (M), M + D (Notch signaling inhibition), M + W (autophagy inhibition), and M + R (autophagy induction) groups. Lyophilized protein powder from pigeon shedding materials was used as an allergen to construct a fibrotic PBL rat model. The mechanism by which Notch signaling regulated autophagy in the pulmonary fibrosis of PBL was investigated by inhibiting the Notch pathway and interfering with autophagy. Pulmonary interstitial fibrosis was significantly greater in the M group and the M + W group than in the M + D and M + R groups. The expression of α-smooth muscle actin was significantly higher in the M, M + D, and M + W groups than in the Ctrl group (P < 0.05). The expression of the cell autophagy markers Beclin1 and LC3 was lower in the M, M + D, and M + W groups than in the Ctrl group (P < 0.05), whereas Beclin1 and LC3 expressions were higher in the M + D and M + R groups than in the M group. The levels of reactive oxygen species in serum and lung tissues were higher in the M, M + D, M + W, and M + R groups than in the Ctrl group (P < 0.05). The Notch signaling pathway is involved in the pathological process of pulmonary fibrosis in the rat model of PBL by regulating autophagy.
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Affiliation(s)
- Yafang Li
- Department of Respiratory and Critical Care Medicine, People’s Hospital of Xinjiang Uygur Autonomous Region, 830001 Urumqi, China,Xinjiang Clinical Research Center for Interstitial Lung Diseases, 830001 Urumqi, China
| | - Zhichuang Lian
- Department of Respiratory and Critical Care Medicine, People’s Hospital of Xinjiang Uygur Autonomous Region, 830001 Urumqi, China
| | - Qifeng Li
- Department of Respiratory and Critical Care Medicine, People’s Hospital of Xinjiang Uygur Autonomous Region, 830001 Urumqi, China
| | - Wei Ding
- Department of Respiratory and Critical Care Medicine, People’s Hospital of Xinjiang Uygur Autonomous Region, 830001 Urumqi, China
| | - Wenyi Wang
- Department of Respiratory and Critical Care Medicine, People’s Hospital of Xinjiang Uygur Autonomous Region, 830001 Urumqi, China
| | - Ling Zhang
- Department of Respiratory and Critical Care Medicine, People’s Hospital of Xinjiang Uygur Autonomous Region, 830001 Urumqi, China
| | - Xirennayi Muhataer
- Department of Respiratory and Critical Care Medicine, People’s Hospital of Xinjiang Uygur Autonomous Region, 830001 Urumqi, China
| | - Yuan Zhou
- Department of Respiratory and Critical Care Medicine, People’s Hospital of Xinjiang Uygur Autonomous Region, 830001 Urumqi, China
| | - Xiaohong Yang
- Department of Respiratory and Critical Care Medicine, People’s Hospital of Xinjiang Uygur Autonomous Region, 830001 Urumqi, China,Xinjiang Clinical Research Center for Interstitial Lung Diseases, 830001 Urumqi, China
| | - Chao Wu
- Department of Respiratory and Critical Care Medicine, People’s Hospital of Xinjiang Uygur Autonomous Region, 830001 Urumqi, China,Xinjiang Clinical Research Center for Interstitial Lung Diseases, 830001 Urumqi, China
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Sánchez-Díez S, Cruz MJ, de Homdedeu M, Ojanguren I, Romero-Mesones C, Sansano I, Muñoz X. Immunopathological Mechanisms of Bird-Related Hypersensitivity Pneumonitis. Int J Mol Sci 2023; 24:ijms24032884. [PMID: 36769205 PMCID: PMC9917634 DOI: 10.3390/ijms24032884] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Revised: 01/27/2023] [Accepted: 01/28/2023] [Indexed: 02/05/2023] Open
Abstract
Bird-related hypersensitivity pneumonitis (BRHP) is an interstitial lung disease induced by avian proteins. The immunopathological pathways involved in the disease are still unknown. This study assesses the cellular immune response and the cytokine pattern in a mouse model of BRHP. On days -3 and -1, mice were intraperitoneally sensitized with commercial pigeon serum (PS) or saline. Intranasal instillations with PS or saline were carried out on three consecutive days/week over either 3 weeks (Group 1) or 12 weeks (Group 2). Leukocyte and cytokine patterns in lung tissue and pulmonary inflammation in bronchoalveolar lavage (BAL) were analysed. Both groups presented increases in resident monocytes, interstitial macrophages and type 2 dendritic cells (DCs), but also reductions in inflammatory monocytes, alveolar macrophages and tolerogenic DCs compared with their control groups. Group 1 had increased levels of eosinophils and T cells with reductions in neutrophils and B cells, while Group 2 showed high levels of B cells. Both groups exhibited increases in Th1 and Th2 cytokines. Group 2 also showed increased levels of IL-23, a Th17 cytokine. Increased levels of neutrophils, eosinophils and lymphocytes were observed in BAL samples of both groups compared with controls. In the first stages of BRHP, there is a mixed Th1/Th2 immune response, while during the progression of the disease, although there is a Th1 response, the cytokine levels seem to indicate a switch towards a Th2/Th17 mixed response.
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Affiliation(s)
- Silvia Sánchez-Díez
- Pulmonology Service, Department of Medicine, Vall d’Hebron University Hospital, Autonomous University of Barcelona, 08035 Barcelona, Spain
- CIBER of Respiratory Diseases (CIBERES), 28029 Madrid, Spain
| | - María Jesús Cruz
- Pulmonology Service, Department of Medicine, Vall d’Hebron University Hospital, Autonomous University of Barcelona, 08035 Barcelona, Spain
- CIBER of Respiratory Diseases (CIBERES), 28029 Madrid, Spain
- Correspondence:
| | - Miquel de Homdedeu
- Pulmonology Service, Department of Medicine, Vall d’Hebron University Hospital, Autonomous University of Barcelona, 08035 Barcelona, Spain
- CIBER of Respiratory Diseases (CIBERES), 28029 Madrid, Spain
| | - Iñigo Ojanguren
- Pulmonology Service, Department of Medicine, Vall d’Hebron University Hospital, Autonomous University of Barcelona, 08035 Barcelona, Spain
- CIBER of Respiratory Diseases (CIBERES), 28029 Madrid, Spain
| | - Christian Romero-Mesones
- Pulmonology Service, Department of Medicine, Vall d’Hebron University Hospital, Autonomous University of Barcelona, 08035 Barcelona, Spain
- CIBER of Respiratory Diseases (CIBERES), 28029 Madrid, Spain
| | - Irene Sansano
- Pathological Anatomy Service, Vall d’Hebron University Hospital, Autonomous University of Barcelona, 08035 Barcelona, Spain
| | - Xavier Muñoz
- Pulmonology Service, Department of Medicine, Vall d’Hebron University Hospital, Autonomous University of Barcelona, 08035 Barcelona, Spain
- CIBER of Respiratory Diseases (CIBERES), 28029 Madrid, Spain
- Department of Cell Biology and Physiology and Immunology, Autonomous University of Barcelona, 08193 Barcelona, Spain
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Tibiletti M, Eaden JA, Naish JH, Hughes PJC, Waterton JC, Heaton MJ, Chaudhuri N, Skeoch S, Bruce IN, Bianchi S, Wild JM, Parker GJM. Imaging biomarkers of lung ventilation in interstitial lung disease from 129Xe and oxygen enhanced 1H MRI. Magn Reson Imaging 2023; 95:39-49. [PMID: 36252693 DOI: 10.1016/j.mri.2022.10.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Revised: 10/07/2022] [Accepted: 10/11/2022] [Indexed: 11/19/2022]
Abstract
PURPOSE To compare imaging biomarkers from hyperpolarised 129Xe ventilation MRI and dynamic oxygen-enhanced MRI (OE-MRI) with standard pulmonary function tests (PFT) in interstitial lung disease (ILD) patients. To evaluate if biomarkers can separate ILD subtypes and detect early signs of disease resolution or progression. STUDY TYPE Prospective longitudinal. POPULATION Forty-one ILD (fourteen idiopathic pulmonary fibrosis (IPF), eleven hypersensitivity pneumonitis (HP), eleven drug-induced ILD (DI-ILD), five connective tissue disease related-ILD (CTD-ILD)) patients and ten healthy volunteers imaged at visit 1. Thirty-four ILD patients completed visit 2 (eleven IPF, eight HP, ten DIILD, five CTD-ILD) after 6 or 26 weeks. FIELD STRENGTH/SEQUENCE MRI was performed at 1.5 T, including inversion recovery T1 mapping, dynamic MRI acquisition with varying oxygen levels, and hyperpolarised 129Xe ventilation MRI. Subjects underwent standard spirometry and gas transfer testing. ASSESSMENT Five 1H MRI and two 129Xe MRI ventilation metrics were compared with spirometry and gas transfer measurements. STATISTICAL TEST To evaluate differences at visit 1 among subgroups: ANOVA or Kruskal-Wallis rank tests with correction for multiple comparisons. To assess the relationships between imaging biomarkers, PFT, age and gender, at visit 1 and for the change between visit 1 and 2: Pearson correlations and multilinear regression models. RESULTS The global PFT tests could not distinguish ILD subtypes. Percentage ventilated volumes were lower in ILD patients than in HVs when measured with 129Xe MRI (HV 97.4 ± 2.6, CTD-ILD: 91.0 ± 4.8 p = 0.017, DI-ILD 90.1 ± 7.4 p = 0.003, HP 92.6 ± 4.0 p = 0.013, IPF 88.1 ± 6.5 p < 0.001), but not with OE-MRI. 129Xe reported more heterogeneous ventilation in DI-ILD and IPF than in HV, and OE-MRI reported more heterogeneous ventilation in DI-ILD and IPF than in HP or CTD-ILD. The longitudinal changes reported by the imaging biomarkers did not correlate with the PFT changes between visits. DATA CONCLUSION Neither 129Xe ventilation nor OE-MRI biomarkers investigated in this study were able to differentiate between ILD subtypes, suggesting that ventilation-only biomarkers are not indicated for this task. Limited but progressive loss of ventilated volume as measured by 129Xe-MRI may be present as the biomarker of focal disease progresses. OE-MRI biomarkers are feasible in ILD patients and do not correlate strongly with PFT. Both OE-MRI and 129Xe MRI revealed more spatially heterogeneous ventilation in DI-ILD and IPF.
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Affiliation(s)
- Marta Tibiletti
- Bioxydyn Limited, Rutherford House, Manchester Science Park, Manchester M15 6SZ, United Kingdom
| | - James A Eaden
- POLARIS, University of Sheffield MRI Unit, Department of Infection, Immunity and Cardiovascular Disease, The University of Sheffield, Sheffield, UK
| | - Josephine H Naish
- Bioxydyn Limited, Rutherford House, Manchester Science Park, Manchester M15 6SZ, United Kingdom; MCMR, Manchester University NHS Foundation Trust, Wythenshawe, Manchester, UK
| | - Paul J C Hughes
- POLARIS, University of Sheffield MRI Unit, Department of Infection, Immunity and Cardiovascular Disease, The University of Sheffield, Sheffield, UK
| | - John C Waterton
- Bioxydyn Limited, Rutherford House, Manchester Science Park, Manchester M15 6SZ, United Kingdom; Centre for Imaging Sciences, University of Manchester, Manchester, UK
| | - Matthew J Heaton
- Bioxydyn Limited, Rutherford House, Manchester Science Park, Manchester M15 6SZ, United Kingdom
| | - Nazia Chaudhuri
- North West Lung Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
| | - Sarah Skeoch
- Royal National Hospital for Rheumatic Diseases, Royal United Hospitals Bath NHS Foundation Trust, Bath, UK
| | - Ian N Bruce
- NIHR Manchester Biomedical Research Centre, Manchester University Hospitals NHS Foundation Trust, Manchester, UK; Centre for Musculoskeletal Research, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK
| | - Stephen Bianchi
- Academic Directorate of Respiratory Medicine, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - Jim M Wild
- POLARIS, University of Sheffield MRI Unit, Department of Infection, Immunity and Cardiovascular Disease, The University of Sheffield, Sheffield, UK; Insigneo Insititute for in silico medicine, Sheffield, UK
| | - Geoff J M Parker
- Bioxydyn Limited, Rutherford House, Manchester Science Park, Manchester M15 6SZ, United Kingdom; Centre for Medical Image Computing, Department of Medical Physics and Biomedical Engineering, University College London, London, UK.
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Coelho DB, Santos V, Alexandre AT, Bastos HNE, Mota PC, Morais A, Melo N. Risk Factors for Acute Exacerbations of Fibrotic Hypersensitivity Pneumonitis-Is Exposure a Trigger That We're Missing? Arch Bronconeumol 2023; 59:59-60. [PMID: 35945072 DOI: 10.1016/j.arbres.2022.07.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Revised: 07/06/2022] [Accepted: 07/07/2022] [Indexed: 01/05/2023]
Affiliation(s)
- David Barros Coelho
- Pulmonology Department, Centro Hospitalar Universitário de São João, Porto, Portugal; Faculty of Medicine, University of Porto, Porto, Portugal.
| | - Vanessa Santos
- Pulmonology Department, Centro Hospitalar Universitário de São João, Porto, Portugal
| | | | - Helder Novais E Bastos
- Pulmonology Department, Centro Hospitalar Universitário de São João, Porto, Portugal; Faculty of Medicine, University of Porto, Porto, Portugal; Instituto de Investigação e Inovação em Saúde I3S, University of Porto, Porto, Portugal
| | - Patrícia Caetano Mota
- Pulmonology Department, Centro Hospitalar Universitário de São João, Porto, Portugal; Faculty of Medicine, University of Porto, Porto, Portugal; Instituto de Investigação e Inovação em Saúde I3S, University of Porto, Porto, Portugal
| | - António Morais
- Pulmonology Department, Centro Hospitalar Universitário de São João, Porto, Portugal; Faculty of Medicine, University of Porto, Porto, Portugal; Instituto de Investigação e Inovação em Saúde I3S, University of Porto, Porto, Portugal
| | - Natália Melo
- Pulmonology Department, Centro Hospitalar Universitário de São João, Porto, Portugal
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Zo S, Chung MP, Yoo HY, Lee KS, Han J, Chung MJ, Yoo H. Clinical characteristics and outcomes of hypersensitivity pneumonitis in South Korea. Ther Adv Respir Dis 2023; 17:17534666231212304. [PMID: 37970818 PMCID: PMC10655655 DOI: 10.1177/17534666231212304] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Accepted: 10/19/2023] [Indexed: 11/19/2023] Open
Abstract
BACKGROUND Hypersensitivity pneumonitis (HP) is an interstitial lung disease (ILD) that results from an immune-mediated reaction involving various antigens in susceptible individuals. However, the clinical characteristics and outcomes of HP in South Korea are not well understood. OBJECTIVES This study was conducted to identify the clinical characteristics and outcomes of HP in South Korea. DESIGN This is a retrospective observational study investigating patients with pathologically confirmed HP at our center, along with a comprehensive review of published HP cases in the Republic of Korea. METHODS This retrospective study analyzed 43 patients with pathologically proven HP at a single tertiary hospital in Korea between 1996 and 2020. In addition, case reports of HP published in Korea were collected. The clinical characteristics, etiologies, treatment, and outcomes of patients from our center, as well as case reports, were reviewed. Patients from our hospital were divided into fibrotic and nonfibrotic subtypes according to the ATS/JRS/ALAT guidelines. RESULTS Among 43 patients with biopsy-proven HP, 12 (27.9%) and 31 (72.1%) patients were classified into the fibrotic and nonfibrotic subtypes, respectively. The fibrotic HP group was older (64.6 ± 8.5 versus 55.2 ± 8.3, p = 0.002) with less frequent complaints of fever (0% versus 45.2%, p = 0.013) compared to the nonfibrotic HP group. The most common inciting antigen was household mold (21, 48.8%), followed by inorganic substances (6, 14.0%). Inciting antigens were not identified in eight (18.6%) patients. Treatment of corticosteroids was initiated in 34 (79.1%) patients. An analysis of 46 patients from Korea by literature review demonstrated that reported cases were relatively younger and drugs were the most common etiology compared to our cohort. CONCLUSION The analysis of reported cases, as well as our cohort, showed that exposure history and clinical manifestations are heterogeneous for patients with HP in South Korea.
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Affiliation(s)
- Sungmin Zo
- Division of Pulmonary, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Man Pyo Chung
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Hak Young Yoo
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Kyung Soo Lee
- Department of Radiology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Joungho Han
- Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Myung Jin Chung
- Department of Radiology and Center for Imaging Sciences, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Hongseok Yoo
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Republic of Korea
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44
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Seixas E, Ferreira M, Serra P, Aguiar R, Cunha I, Ferreira PG. Criteria for progressive fibrotic hypersensitivity pneumonitis in a Portuguese patient cohort. Afr J Thorac Crit Care Med 2022; 28:10.7196/AJTCCM.2022.v28i4.250. [PMID: 36817315 PMCID: PMC9929648 DOI: 10.7196/ajtccm.2022.v28i4.250] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/27/2022] [Indexed: 12/24/2022] Open
Abstract
Background Hypersensitivity pneumonitis (HP) is a syndrome caused by sensitisation to inhaled antigens that leads to an abnormal immune response in the airways and lung parenchyma. Some patients previously diagnosed with certain types of fibrotic interstitial lung diseases (f-ILDs), including fibrotic HP (f-HP), are susceptible to develop a progressive fibrosing phenotype (PF-ILD), despite initial state-of-the-art management. Objectives To characterise a cohort of patients with a multidisciplinary diagnosis (MTD) of chronic f-HP, who were followed up in an ILD outpatient clinic of a hospital in Portugal, and to assess the prevalence of PF-ILD criteria in these patients. Methods Data were collected from all patients with a definite or provisional diagnosis of f-HP after a multidisciplinary team discussion. Patients were followed up between December 2014 and July 2019. Data included clinical characteristics, high-resolution chest tomography (HRCT) disease patterns, lung function tests, bronchoalveolar lavage and further immunological work-up, biopsy reports (conventional transbronchial lung biopsy, transbronchial lung cryobiopsy or surgical video-assisted thoracoscopic lung biopsy), all ILD multidisciplinary team records and diagnostic confidence levels. Patients were assessed according to PF-ILD criteria as defined in the INBUILD trial. Results We identified 83 patients with an MTD of HP, who had been followed up for at least 12 months. Of these, 63 (75.9%) were diagnosed with f-HP. Of the 63 f-HP patients, 33.3% (n=21) fulfilled the predefined criteria for PF-HP: 66.7% had a relative decline of ≥10% forced vital capacity (FVC); 5% a relative decline of 5 - 9% FVC, with worsening symptoms or increased fibrosis on HRCT; and 23.8% had worsening respiratory symptoms with radiological progression. Conclusion This single-centre cohort study demonstrated that a third of f-HP patients presented with PF-ILD, as determined by progression during initial standard-of-care treatment. A usual interstitial pneumonia (UIP)/UIP-like pattern was present in >70% of patients with f-HP, and two-thirds of these patients had an FVC decline of ≥10%. PF-HP patients were also more exacerbation prone. According to recent trial data, this segment of patients can be considered possible candidates for antifibrotic treatment, with a reasonable prospect of effectiveness. Further efforts should focus on refining knowledge of longitudinal behaviour of large multicentric cohorts of f-HP patients, establishing a consensual and uniform definition of progression for use in clinical practice, as well as developing prognostic prediction tools to better (and early) inform the disease course.
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Affiliation(s)
- E Seixas
- Department of Pulmonology, Centro Hospitalar Baixo Vouga, Aveiro, Portugal
| | - M Ferreira
- Department of Radiology, Centro Hospitalar Baixo Vouga, Aveiro, Portugal
| | - P Serra
- Department of Pathology, Centro Hospitalar Baixo Vouga, Aveiro, Portugal
| | - R Aguiar
- Department of Rheumatology, Centro Hospitalar Baixo Vouga, Aveiro, Portugal
| | - I Cunha
- Department of Rheumatology, Centro Hospitalar Baixo Vouga, Aveiro, Portugal
| | - P G Ferreira
- Department of Pulmonology, Centro Hospitalar e Universitário de Coimbra, Portugal
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45
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Mendonça Almeida L, Fernandes AL, Gouveia Cardoso C, Lima B, Neves I, Novais-Bastos H, Caetano Mota P, Melo N, Souto Moura C, Guimarães S, Carvalho A, Cunha R, Pereira JM, Morais A. Mortality risk prediction with ILD-GAP index in a fibrotic hypersensitivity pneumonitis cohort. Ther Adv Respir Dis 2022; 16:17534666221135316. [PMID: 36476249 PMCID: PMC9742694 DOI: 10.1177/17534666221135316] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Fibrotic hypersensitivity pneumonitis (fHP) is associated with significant morbidity and mortality. Interstitial lung disease-gender-age-physiology (ILD-GAP) performance in fHP outside the initial cohort was never performed. AIM To assess the ILD-GAP index's ability to predict mortality in a Portuguese cohort of patients with fHP and analyse whether other clinical variables add value. METHODS Retrospective analysis of fHP cohort in two Portuguese ILD centres. The baseline ILD-GAP index was calculated. Survival was analysed in months; mortality was the primary outcome. Univariate and multivariate analyses to identify mortality risk factors were performed. RESULTS A total of 141 patients were included. Fifty-three patients (37.6%) died during the follow-up. The usual interstitial pneumonia (UIP) pattern was found in 49.6%, and their survival was inferior to non-UIP [32 months (interquartile range, IQR = 19, 60) versus 52 months (IQR = 28, 98), p = 0.048]. Patients with an ILD-GAP index higher than three double their risk of mortality [hazard ratio (HR) = 6.48, 95% confidence interval (CI) = (3.03-13.96)] when compared with the patients with an index between 2 and 3 [HR = 3.04, 95% CI = (1.62-5.71)] adjusting for acute exacerbation history. Even though UIP patients had worse survival, it did not reach statistical significance when UIP pattern was added to this model. Acute exacerbation history was an independent risk factor for mortality; however, ILD-GAP still predicted mortality after adjusting for this factor. PaO2 and 6-minute walk test desaturation were not significant risk factors. CONCLUSION ILD-GAP index is a good predictor for mortality in fHP, even after adjusting for other mortality risk factors.
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Affiliation(s)
| | | | | | - Bruno Lima
- Oficina de Bioestatística, Porto, Portugal
| | - Inês Neves
- Pulmonology Department, Hospital Pedro Hispano, Matosinhos, Portugal
| | - Hélder Novais-Bastos
- Pulmonology Department, Centro Hospitalar e Universitário São João, Porto, Portugal,Faculty of Medicine, University of Porto, Porto, Portugal,i3S – Institute for Research and Innovation in Health/Instituto de Investigação e Inovação em Saúde da Universidade do Porto, Porto, Portugal
| | - Patrícia Caetano Mota
- Pulmonology Department, Centro Hospitalar e Universitário São João, Porto, Portugal,Faculty of Medicine, University of Porto, Porto, Portugal
| | - Natália Melo
- Pulmonology Department, Centro Hospitalar e Universitário São João, Porto, Portugal
| | - Conceição Souto Moura
- Faculty of Medicine, University of Porto, Porto, Portugal,Pathology Department, Centro Hospitalar e Universitário São João, Porto, Portugal
| | - Susana Guimarães
- Faculty of Medicine, University of Porto, Porto, Portugal,Pathology Department, Centro Hospitalar e Universitário São João, Porto, Portugal
| | - André Carvalho
- Faculty of Medicine, University of Porto, Porto, Portugal,Radiology Department, Centro Hospitalar e Universitário São João, Porto, Portugal
| | - Rui Cunha
- Faculty of Medicine, University of Porto, Porto, Portugal,Radiology Department, Centro Hospitalar e Universitário São João, Porto, Portugal
| | - José Miguel Pereira
- Faculty of Medicine, University of Porto, Porto, Portugal,Radiology Department, Centro Hospitalar e Universitário São João, Porto, Portugal
| | - António Morais
- Pulmonology Department, Centro Hospitalar e Universitário São João, Porto, Portugal,Faculty of Medicine, University of Porto, Porto, Portugal,i3S – Institute for Research and Innovation in Health/Instituto de Investigação e Inovação em Saúde da Universidade do Porto, Porto, Portugal
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46
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He J, Zhang J, Ren X. Krebs von den lungen-6 as a clinical marker for hypersensitivity pneumonitis: A meta-analysis and bioinformatics analysis. Front Immunol 2022; 13:1041098. [PMID: 36532009 PMCID: PMC9748086 DOI: 10.3389/fimmu.2022.1041098] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2022] [Accepted: 11/14/2022] [Indexed: 12/05/2022] Open
Abstract
Aim Hypersensitivity pneumonitis (HP), also referred to as exogenous allergic alveolitis, is one of the most common interstitial lung diseases (ILDs). A potential immune biomarker, Krebs von den lgen-6 (KL-6) characterizes the progression and severity of HP. The meta-analysis in this study was conducted to elucidate the variations in the concentrations of KL-6 in different types of HP. Methods A systematic search of various databases such as EMBASE, Pubmed, CNKI, VIP, Web of Science, and WanFang was carried out to find relevant published articles between January 1980 and August 2022 that explored the relationship between KL-6 and allergic pneumonia. Standardized mean difference (SMD) and 95% confidence interval (CI) were used as effect sizes for comparison among different groups. The GSE47460 and GSE150910 datasets were downloaded to extract and validate the differences in KL-6 mRNA expression between HP lung tissue and healthy controls. Furthermore, the single-cell sequencing dataset GSE135893 was downloaded to extract KL-6 mRNA expression in type II alveolar epithelial cells to validate the differences between HP and healthy controls. Two researchers evaluated the quality of the included studies by employing Newcastle-Ottawa Scale. All the qualified studies were subjected to statistical analyses carried out utilizing RevMan 5.2, Stata 11.0, and R software 4.1.3. Results Twenty studies aligned perfectly with the inclusion criteria of the meta. The concentrations of KL-6 were substantially higher in the blood of HP patients as compared to the control group. Subgroup analyses were carried out in accordance with the allergen source and the results revealed that patients with different allergens had higher blood KL-6 concentrations than healthy controls. Additionally, different subgroups of subjects were created for meta-analysis as per the fibrosis status, race, measurement method, and sample type. The concentration of KL-6 in blood was much higher in all HP subgroups than in healthy control groups. Moreover, the bioinformatics analysis revealed that KL-6 mRNA expression was higher in HP lung tissue and type II alveolar epithelial cells as compared to healthy controls. Conclusion The present meta-analysis and bioinformatics analysis suggested that the concentration levels of KL-6 varied between HP patients and healthy individuals, and the KL-6 concentrations may be higher in the blood samples of HP patients. Systematic review registration https://www.crd.york.ac.uk/prospero/, CRD42022355334.
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Affiliation(s)
- Jie He
- Clinical Medical College of Chengdu Medical College. Chengdu, Sichuan, China,Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China,*Correspondence: Jie He,
| | - Jiangliu Zhang
- Clinical Medical College of Chengdu Medical College. Chengdu, Sichuan, China,Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China
| | - Xinyi Ren
- Clinical Medical College of Chengdu Medical College. Chengdu, Sichuan, China,Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China
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Ionescu MD, Popescu NA, Stănescu D, Enculescu A, Bălgrădean M, Căpitănescu GM, Bumbăcea D. The Challenging Diagnosis of Interstitial Lung Disease in Children-One Case Report and Literature Review. J Clin Med 2022; 11:jcm11226736. [PMID: 36431212 PMCID: PMC9698870 DOI: 10.3390/jcm11226736] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2022] [Revised: 11/08/2022] [Accepted: 11/10/2022] [Indexed: 11/16/2022] Open
Abstract
Childhood interstitial lung disease (chILD) includes a heterogeneous spectrum of rare respiratory disorders in children associated with substantial morbi-mortality. Interstitial tissue, and other pulmonary structures, epithelium, blood vessels, or pleura are involved, resulting in a restrictive lung disfunction. Respiratory symptoms set in progressively and are often subtle, making thorough clinical history and physical examination fundamental. The etiology often is obscure. The clinical presentation mimics pneumonia or asthma, leading to a diagnostic delay. Challenging diagnosis may require genetic tests, bronchoalveolar lavage, or lung biopsy. Alongside general supportive therapeutic measures, anti-inflammatory, immunosuppressive or antifibrotic agents may be used, based on data derived from adult studies. However, if accurate diagnosis and treatment are delayed, irreversible chronic respiratory failure may ensue, impacting prognosis. The most frequent chILD is hypersensitivity pneumonitis (HP), although it is rare in children. HP is associated with exposure to an environmental antigen, resulting in inflammation of the airways. Detailed antigen exposure history and identification of the inciting trigger are the cornerstones of diagnostic. This article provides the current state of chILD, revealing specific features of HP, based on a clinical case report of a patient admitted in our clinic, requiring extensive investigations for diagnosis, with a favorable long-term outcome.
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Affiliation(s)
- Marcela Daniela Ionescu
- Department of Pediatrics, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania
- “Marie S. Curie” Emergency Children’s Clinical Hospital, 041451 Bucharest, Romania
| | | | - Diana Stănescu
- “Marie S. Curie” Emergency Children’s Clinical Hospital, 041451 Bucharest, Romania
| | - Augustina Enculescu
- “Marie S. Curie” Emergency Children’s Clinical Hospital, 041451 Bucharest, Romania
| | - Mihaela Bălgrădean
- Department of Pediatrics, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania
- “Marie S. Curie” Emergency Children’s Clinical Hospital, 041451 Bucharest, Romania
| | | | - Dragos Bumbăcea
- Department of Cardio-Thoracic Medicine, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania
- Department of Pneumology and Acute Respiratory Care, Elias Emergency University Hospital, 041451 Bucharest, Romania
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Koster MA. Hypersensitivity Pneumonitis: An Updated Diagnostic Guide for Internists. Med Clin North Am 2022; 106:1055-1065. [PMID: 36280332 DOI: 10.1016/j.mcna.2022.08.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
This summary highlights updated definitions, terminology, and classification systems proposed in the diagnosis of hypersensitivity pneumonitis. Clinical presentation, epidemiology, and pathophysiology are reviewed from the most recent data. Radiographic and histopathologic diagnostic criteria are presented in a manner relevant to the practice of general medicine internists, including new guideline recommendations. The role of adjunctive tests, such as serum IgG testing, bronchoalveolar lavage lymphocyte analysis, and pulmonary function testing is discussed in the context of supporting diagnostic confidence for hypersensitivity pneumonitis diagnosis. Finally, new diagnostic algorithms are synthesized and applied to the general internal medicine setting.
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Affiliation(s)
- Megan A Koster
- Division of Pulmonary and Critical Care, Department of Medicine, Mount Auburn Hospital, Harvard Medical School, 300 Mount Auburn Street, # 419, Cambridge, MA 02138, USA.
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49
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Updated Imaging Classification of Hypersensitivity Pneumonitis. Radiol Clin North Am 2022; 60:901-913. [DOI: 10.1016/j.rcl.2022.06.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
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New Paradigms in Hypersensitivity Pneumonitis. CURRENT PULMONOLOGY REPORTS 2022. [DOI: 10.1007/s13665-022-00295-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
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