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Morimoto K, Daley CL. Comprehensive Management Algorithm for Mycobacterium avium Complex Pulmonary Disease in the Real-World Setting. Ann Am Thorac Soc 2025; 22:651-659. [PMID: 39933174 PMCID: PMC12051929 DOI: 10.1513/annalsats.202408-904fr] [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: 08/31/2024] [Accepted: 02/10/2025] [Indexed: 02/13/2025] Open
Abstract
The management of Mycobacterium avium complex pulmonary disease (MAC-PD) is challenging because of limited efficacy and frequent adverse events associated with standard treatments. The 2020 guidelines from the American Thoracic Society, European Respiratory Society, European Society of Clinical Microbiology and Infectious Diseases, and Infectious Diseases Society of America provide recommendations, but real-world adherence is often hindered by these issues, leading many patients to be unable to complete standard therapy. This review proposes a comprehensive management algorithm for MAC-PD, emphasizing multidisciplinary approaches and integrating nonantimicrobial management before, during, and after drug treatment to enhance patient outcomes. When a patient presents with chronic respiratory symptoms suggestive of nontuberculous mycobacteria, clinicians should follow a guideline-based approach to diagnosis, as diagnostic delays are common because of nonspecific symptoms. Proper evaluation should determine the disease phenotype (existence of cavitary lesions), as it influences treatment choices. Airway clearance, nutritional support, and management of underlying conditions are essential nonantimicrobial components. Regular outpatient monitoring helps detect disease progression and optimize treatment. Treatment strategies vary based on disease severity. For noncavitary nodular bronchiectatic disease, a thrice-weekly regimen is preferred because of better tolerability. Severe cases or those with cavitary forms may require daily treatment with additional aminoglycosides. Amikacin liposome inhalation suspension is recommended for patients not responding to standard regimens after 6 months. Recent research addresses drug intolerance, suggesting alternatives such as a two-drug regimen without rifamycin in certain cases. Consultation with nontuberculous mycobacteria specialists is advised for complex cases, particularly those with macrolide resistance or requiring surgical intervention. The algorithm emphasizes shared decision making, patient education, and family support to improve adherence and outcomes.
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Affiliation(s)
- Kozo Morimoto
- Respiratory Disease Center and
- Division of Clinical Research, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan
- Department of Clinical Mycobacteriosis, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Charles L. Daley
- Department of Medicine, National Jewish Health, Denver, Colorado; and
- Department of Medicine, University of Colorado, Aurora, Colorado
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Opolot EE, Goshevski F, Chaudhary R, Kilgore JA, Williams NS, von Recum HA, Desai AB. Sustained Release of Antifibrotic Nintedanib from Polymer Microparticles Reduces Dosing Frequency While Reducing Inflammation in Murine Idiopathic Pulmonary Fibrosis. Ann Biomed Eng 2025:10.1007/s10439-025-03729-8. [PMID: 40210794 DOI: 10.1007/s10439-025-03729-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2024] [Accepted: 03/29/2025] [Indexed: 04/12/2025]
Abstract
PURPOSE Idiopathic pulmonary fibrosis (IPF) is a life-threatening, progressive lung disease with limited therapeutic options, often resulting in poor patient outcomes. Current treatments, such as Nintedanib (NTB) and Pirfenidone (PFD), require frequent administration, leading to adverse effects and low patient adherence. The purpose of this study was to investigate a sustained-release drug delivery system utilizing microparticles (MPs) composed of insoluble beta-cyclodextrin (β-CD) polymers to enhance the bioavailability and extend the release of NTB and PFD. METHODS A multidisciplinary approach, including in silico modeling, in vitro assays, and in vivo studies, was employed to assess the efficacy of β-CD-polymer MPs as drug carriers. RESULTS Molecular docking simulations and surface plasmon resonance studies demonstrated a stronger binding affinity of NTB to β-CD-polymer MPs compared to PFD, suggesting an extended delivery profile for NTB over PFD. Pharmacokinetic analysis in healthy mice confirmed sustained-release profiles for both drugs, with NTB maintaining therapeutic plasma concentrations for over 70 h. In a bleomycin-induced IPF mouse model, NTB-loaded β-CD-polymer MPs significantly reduced pro-inflammatory markers and required fewer injections than the standard daily NTB regimen. CONCLUSION These findings indicate that β-CD-polymer MPs may serve as a promising platform for reducing dosing frequency of NTB and enhancing therapeutic outcomes in the treatment of IPF.
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Affiliation(s)
- Emmanuel Einyat Opolot
- Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA
| | - Filip Goshevski
- Department of Medicine and Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA
| | - Rahul Chaudhary
- Department of Medicine and Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA
| | - Jessica A Kilgore
- Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Noelle S Williams
- Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Horst A von Recum
- Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA.
| | - Amar B Desai
- Department of Medicine and Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA.
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Licata MA, Monteleone G, Schiavi E, Musso M, Mencarini P, Mastrobattista A, Carli SM, Cerva C, Sgalla G, Richeldi L, Palmieri F, Gualano G. Usual Interstitial Pneumonia Pattern and Mycobacteria Lung Diseases: A Case Series. Infect Dis Rep 2025; 17:28. [PMID: 40277955 PMCID: PMC12026791 DOI: 10.3390/idr17020028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2025] [Revised: 03/28/2025] [Accepted: 03/31/2025] [Indexed: 04/26/2025] Open
Abstract
BACKGROUND Interstitial lung diseases (ILDs) are a heterogeneous group of conditions that can cause fibrosis of the lung interstitium, resulting in respiratory failure and death. Patients with an ILD, particularly idiopathic pulmonary fibrosis (IPF) or connective tissue disease-associated ILDs (CTD-ILDs), are prone to develop chronic pulmonary infections such as tuberculosis (TB) and non-tuberculous mycobacterial pulmonary disease (NTM-PD). METHODS This case series examines the management of three ILD patients with a usual interstitial pneumonia (UIP) pattern and concomitant NTM-PD or TB at National Institute for Infectious Diseases "Lazzaro Spallanzani" in Rome, Italy, over three years (2019-2022). RESULTS AND CONCLUSIONS Multi-disciplinary discussion (MDD) was crucial to define the therapeutic approach due to the increased risk of side effects and drug interactions. Our work underscored how a comprehensive diagnostic evaluation, enriched by MDD, is useful for optimizing the management and reducing drug-related adverse effects and interactions in ILD patients with cavitary lesions.
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Affiliation(s)
- Maria Angela Licata
- Department of Neurosciences, Sense Organs, and Thorax, Catholic University of the Sacred Heart, 00153 Rome, Italy; (M.A.L.); (G.M.); (E.S.); (G.S.); (L.R.)
- Pulmonology Unit and UTIR, Ospedale Civile San Salvatore, 67100 L’Aquila, Italy
| | - Giorgio Monteleone
- Department of Neurosciences, Sense Organs, and Thorax, Catholic University of the Sacred Heart, 00153 Rome, Italy; (M.A.L.); (G.M.); (E.S.); (G.S.); (L.R.)
| | - Enrico Schiavi
- Department of Neurosciences, Sense Organs, and Thorax, Catholic University of the Sacred Heart, 00153 Rome, Italy; (M.A.L.); (G.M.); (E.S.); (G.S.); (L.R.)
| | - Maria Musso
- Respiratory Infectious Diseases Unit, National Institute for Infectious Diseases “Lazzaro Spallanzani” IRCCS, 00149 Rome, Italy; (P.M.); (A.M.); (S.M.C.); (C.C.); (F.P.); (G.G.)
| | - Paola Mencarini
- Respiratory Infectious Diseases Unit, National Institute for Infectious Diseases “Lazzaro Spallanzani” IRCCS, 00149 Rome, Italy; (P.M.); (A.M.); (S.M.C.); (C.C.); (F.P.); (G.G.)
| | - Annelisa Mastrobattista
- Respiratory Infectious Diseases Unit, National Institute for Infectious Diseases “Lazzaro Spallanzani” IRCCS, 00149 Rome, Italy; (P.M.); (A.M.); (S.M.C.); (C.C.); (F.P.); (G.G.)
| | - Serena Maria Carli
- Respiratory Infectious Diseases Unit, National Institute for Infectious Diseases “Lazzaro Spallanzani” IRCCS, 00149 Rome, Italy; (P.M.); (A.M.); (S.M.C.); (C.C.); (F.P.); (G.G.)
| | - Carlotta Cerva
- Respiratory Infectious Diseases Unit, National Institute for Infectious Diseases “Lazzaro Spallanzani” IRCCS, 00149 Rome, Italy; (P.M.); (A.M.); (S.M.C.); (C.C.); (F.P.); (G.G.)
| | - Giacomo Sgalla
- Department of Neurosciences, Sense Organs, and Thorax, Catholic University of the Sacred Heart, 00153 Rome, Italy; (M.A.L.); (G.M.); (E.S.); (G.S.); (L.R.)
- Complex Operative Unit of Pulmonology, Department of Neurosciences, Sense Organs, and Thorax, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Agostino Gemelli 8, 00168 Rome, Italy
| | - Luca Richeldi
- Department of Neurosciences, Sense Organs, and Thorax, Catholic University of the Sacred Heart, 00153 Rome, Italy; (M.A.L.); (G.M.); (E.S.); (G.S.); (L.R.)
- Complex Operative Unit of Pulmonology, Department of Neurosciences, Sense Organs, and Thorax, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Agostino Gemelli 8, 00168 Rome, Italy
| | - Fabrizio Palmieri
- Respiratory Infectious Diseases Unit, National Institute for Infectious Diseases “Lazzaro Spallanzani” IRCCS, 00149 Rome, Italy; (P.M.); (A.M.); (S.M.C.); (C.C.); (F.P.); (G.G.)
| | - Gina Gualano
- Respiratory Infectious Diseases Unit, National Institute for Infectious Diseases “Lazzaro Spallanzani” IRCCS, 00149 Rome, Italy; (P.M.); (A.M.); (S.M.C.); (C.C.); (F.P.); (G.G.)
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Kim BG, Shin SH, Lee SK, Kim SH, Lee H. Risk of incident chronic obstructive pulmonary disease during longitudinal follow-up in patients with nontuberculous mycobacterial pulmonary disease. Respir Res 2024; 25:333. [PMID: 39252048 PMCID: PMC11384693 DOI: 10.1186/s12931-024-02963-3] [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: 03/27/2024] [Accepted: 08/27/2024] [Indexed: 09/11/2024] Open
Abstract
BACKGROUND The Global Initiative for Chronic Obstructive Lung Disease 2023 revision proposed that chronic obstructive pulmonary disease (COPD) has various etiologies including infections (COPD-I), such as tuberculosis and human immunodeficiency virus. While nontuberculous mycobacterial pulmonary disease (NTM-PD) and pulmonary tuberculosis share similar clinical manifestations, research on COPD development during longitudinal follow-up in patients with NTM-PD is limited. In this study, we aimed to evaluate the incidence and risk of COPD development in patients with NTM-PD. METHODS We retrospectively enrolled patients with NTM-PD with normal lung function and 1:4 age-, sex-, body mass index-, and smoking status-matched controls between November 1994 and January 2022. We compared the risks of spirometry-defined COPD between the NTM-PD and control groups (study 1). A nationwide cohort study using the health insurance claims database was conducted to validate the findings (study 2). RESULTS In study 1, during a mean follow-up of 3.3 years, COPD occurred in 14.0% (241/1,715) and 4.3% (293/6,860) of individuals in the NTM-PD and matched control cohorts, respectively. The NTM-PD cohort exhibited a higher risk of incident COPD (adjusted hazard ratio [aHR], 2.57; 95% CI, 2.15-3.09) compared to matched controls. In study 2, COPD occurred in 6.2% (24/386) and 2.5% (28/1,133) of individuals with and without NTM-PD, respectively. The NTM-PD cohort had a higher risk of incident COPD (aHR, 2.04; 95% CI, 1.21-3.42) compared to matched controls. CONCLUSION These findings suggest that NTM-PD could be considered a new etiotype of COPD-I and emphasize the importance of monitoring lung function in individuals with NTM-PD.
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Affiliation(s)
- Bo-Guen Kim
- Division of Pulmonary Medicine and Allergy, Department of Internal Medicine, Hanyang University College of Medicine, 222-1, Wangsimni-ro, Seongdong-gu, Seoul, 04763, Republic of Korea
- Division of Pulmonary Medicine, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Sun Hye Shin
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Sun-Kyung Lee
- Division of Pulmonary Medicine and Allergy, Department of Internal Medicine, Hanyang University College of Medicine, 222-1, Wangsimni-ro, Seongdong-gu, Seoul, 04763, Republic of Korea
- Department of Mathematics, College of Natural Sciences, Hanyang University, Seoul, Republic of Korea
| | - Sang-Heon Kim
- Division of Pulmonary Medicine and Allergy, Department of Internal Medicine, Hanyang University College of Medicine, 222-1, Wangsimni-ro, Seongdong-gu, Seoul, 04763, Republic of Korea
| | - Hyun Lee
- Division of Pulmonary Medicine and Allergy, Department of Internal Medicine, Hanyang University College of Medicine, 222-1, Wangsimni-ro, Seongdong-gu, Seoul, 04763, Republic of Korea.
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Debi U, Devkota S, Choudhary SR, Sagar S, Karki T, Garg M, Prabhakar N, Dhooria S, Singh N, Bal A. Computed Tomography Spectrum of Complications in Usual Interstitial Pneumonia Pattern in a Tertiary Care Hospital: A Descriptive Cross- sectional Study. JNMA J Nepal Med Assoc 2024; 62:511-515. [PMID: 39369401 PMCID: PMC11455644 DOI: 10.31729/jnma.8706] [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: 07/30/2024] [Indexed: 10/08/2024] Open
Abstract
INTRODUCTION Idiopathic pulmonary fibrosis is the most prevalent form of interstitial lung disease, which presents as usual interstitial pneumonia on histopathology and imaging. It leads to significant lung scarring, damage, and fibrosis and is associated with a high degree of mortality, repeated hospital admissions, and oxygen dependence. Many complications are associated with idiopathic pulmonary fibrosis, which further increases the morbidity of patients. High-resolution computed tomography chest is the imaging modality of choice for usual interstitial pneumonia tracking its progression, evaluating treatment response, and detecting potential complications. METHODS This descriptive cross-sectional study was approved by the Institutional Ethics Committee (Reference number: IEC-INT/2023/Study-1256). Departmental computed tomography report database from November, 2017 to June, 2018 was reviewed and scans with imaging features consistent with the 'usual interstitial pneumonia' pattern were identified. Total sampling method was used and two independent radiologists, blinded to the patient's clinical information, reviewed the high-resolution computed tomography chest scans to assess for imaging features of usual interstitial pneumonia and associated complications. Data was collected and analyzed using Microsoft Excel. RESULTS There were 65 patients reported as unusual interstitial pneumonia pattern. Emphysema and pneumothorax were identified in 4 (6.15%) and 1 (1.53%) scans, respectively. Two (3.08%) scans showed features of pulmonary arterial hypertension. Ten (15.38%) scans exhibited findings consistent with co-existent or superimposed pulmonary infection. Additionally, features of lung malignancy were identified in high-resolution computed tomography scans of 5 (7.69%) patients. CONCLUSIONS Patients with UIP often experience severe lung scarring, and frequent complications, and require regular chest CT scans to monitor disease progression and identify potential complications.
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Affiliation(s)
- Uma Debi
- Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education & Research, Chandigarh, India
| | - Shritik Devkota
- Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education & Research, Chandigarh, India
| | - Shayeri Roy Choudhary
- Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education & Research, Chandigarh, India
| | - Sathya Sagar
- Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education & Research, Chandigarh, India
| | - Tanka Karki
- Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education & Research, Chandigarh, India
| | - Mandeep Garg
- Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education & Research, Chandigarh, India
| | - Nidhi Prabhakar
- Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education & Research, Chandigarh, India
| | - Sahajal Dhooria
- Department of Pulmonary Medicine, Postgraduate Institute of Medical Education & Research, Chandigarh, India
| | - Navneet Singh
- Department of Pulmonary Medicine, Postgraduate Institute of Medical Education & Research, Chandigarh, India
| | - Amanjit Bal
- Department of Histopathology, Postgraduate Institute of Medical Education & Research, Chandigarh, India
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Qi DD, Zhuang Y, Chen Y, Guo JJ, Zhang Z, Gu Y. Interstitial pneumonia combined with nocardia cyriacigeorgica infection: A case report. World J Clin Cases 2023; 11:7920-7925. [DOI: 10.12998/wjcc.v11.i32.7920] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Revised: 10/25/2023] [Accepted: 11/02/2023] [Indexed: 11/16/2023] Open
Abstract
BACKGROUND Nocardia infection is a relatively uncommon disease, with no reports among patients with interstitial pneumonia. Due to its atypical clinical symptoms and chest computed tomography (CT) findings and the frequent yielding of negative results by conventional cultures, it poses challenges for timely diagnosis and treatment.
CASE SUMMARY A 63-year-old female patient presented to our hospital in July 2022 with a 3-mo history of intermittent cough and poor appetite, accompanied by a 2-wk long duration of headaches. She had a previous medical history of interstitial pneumonia and was on oral prednisone and cyclosporine. Chest CT revealed the presence of newly developed round nodules. The diagnosis of Nocardia cyriacigeorgica infection was confirmed through metagenomic next-generation sequencing (mNGS) performed on bronchoalveolar lavage fluid. Targeted anti-infection therapy was initiated, resulting in symptom improvement and radiological resolution, further validating the mNGS results.
CONCLUSION Nocardia cyriacigeorgica infection is a clinically rare condition that is primarily observed in immunocompromised patients. Its clinical and radiological manifestations lack specificity, but mNGS can aid in rapidly obtaining pathogenic information. Early initiation of targeted antimicrobial therapy based on mNGS results can improve patient prognosis.
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Affiliation(s)
- Dao-Da Qi
- Department of Geriatrics, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing 210003, Jiangsu Province, China
| | - Yi Zhuang
- Department of Respiratory and Critical Care Medicine, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210006, Jiangsu Province, China
| | - Yang Chen
- Department of Geriatrics, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing 210003, Jiangsu Province, China
| | - Jing-Jing Guo
- Department of Geriatrics, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing 210003, Jiangsu Province, China
| | - Ze Zhang
- Department of Geriatrics, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing 210003, Jiangsu Province, China
| | - Yan Gu
- Department of Geriatrics, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing 210003, Jiangsu Province, China
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Nishizawa Y, Katsura H, Sasaki Y, Kudo R, Kizuki A, Horimoto A, Ishikawa M, Takagi K, Kikuchi K, Sakura H, Nitta K, Hoshino J, Ogawa T. Secondary spontaneous pneumothorax in a patient with resistant Mycobacterium abscessus infection and systemic sclerosis-associated interstitial lung disease: A case report. Respir Med Case Rep 2023; 46:101941. [PMID: 38025248 PMCID: PMC10661848 DOI: 10.1016/j.rmcr.2023.101941] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Revised: 11/01/2023] [Accepted: 11/01/2023] [Indexed: 12/01/2023] Open
Abstract
Mycobacterium abscessus subsp. abscessus (MABA) is refractory and sometimes fatal especially in an immunocompromised patient. Also, MABA-associated pneumothorax is an extremely rare complication. We report a case of MABA pulmonary infection complicated pneumothorax treated successfully. A 69-year-old Japanese female with immunosuppressed systemic sclerosis-associated interstitial lung disease experienced left-sided secondary spontaneous pneumothorax. MABA was detected in the pleural effusion and blood culture. Microbial sensitivity test showed the MABA was sensitive to only amikacin, sitafloxacin, and clofazimine. Combination therapy with these antibiotics including azithromycin achieved remission within three weeks. In the treatment of MABA infection, compliance with microbial sensitivity test is crucial.
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Affiliation(s)
- Yoko Nishizawa
- Department of Medicine, Tokyo Women's Medical University Adachi Medical Center, 4-33-1, Kohoku, Adachi-ku, Tokyo, 123-8558, Japan
| | - Hideki Katsura
- Department of Medicine, Tokyo Women's Medical University Adachi Medical Center, 4-33-1, Kohoku, Adachi-ku, Tokyo, 123-8558, Japan
- Department of Respiratory Medicine, Tokyo Women's Medical University, 8-1, Kawadacho, Shinjyuku-ku, Tokyo, 162-8666, Japan
| | - Yuka Sasaki
- Center of Pulmonary Disease, National Hospital Organization Tokyo National Hospital, 3-1-1, Takeoka, Kiyose-shi, Tokyo, 204-8585, Japan
| | - Ryoma Kudo
- Department of Medicine, Tokyo Women's Medical University Adachi Medical Center, 4-33-1, Kohoku, Adachi-ku, Tokyo, 123-8558, Japan
| | - Aki Kizuki
- Department of Medicine, Tokyo Women's Medical University Adachi Medical Center, 4-33-1, Kohoku, Adachi-ku, Tokyo, 123-8558, Japan
| | - Ai Horimoto
- Department of Medicine, Tokyo Women's Medical University Adachi Medical Center, 4-33-1, Kohoku, Adachi-ku, Tokyo, 123-8558, Japan
| | - Motonao Ishikawa
- Department of Medicine, Tokyo Women's Medical University Adachi Medical Center, 4-33-1, Kohoku, Adachi-ku, Tokyo, 123-8558, Japan
| | - Kae Takagi
- Department of Medicine, Tokyo Women's Medical University Adachi Medical Center, 4-33-1, Kohoku, Adachi-ku, Tokyo, 123-8558, Japan
| | - Ken Kikuchi
- Department of Infectious Diseases, Tokyo Women's Medical University, 8-1, Kawadacho, Shinjyuku-ku, Tokyo, 162-8666, Japan
| | - Hiroshi Sakura
- Department of Medicine, Tokyo Women's Medical University Adachi Medical Center, 4-33-1, Kohoku, Adachi-ku, Tokyo, 123-8558, Japan
| | - Kosaku Nitta
- Department of Nephrology, Tokyo Women's Medical University, 8-1, Kawadacho, Shinjyuku-ku, Tokyo, 162-8666, Japan
| | - Junichi Hoshino
- Department of Nephrology, Tokyo Women's Medical University, 8-1, Kawadacho, Shinjyuku-ku, Tokyo, 162-8666, Japan
| | - Tetsuya Ogawa
- Department of Medicine, Tokyo Women's Medical University Adachi Medical Center, 4-33-1, Kohoku, Adachi-ku, Tokyo, 123-8558, Japan
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Cao L, Sun Y, Chen F. Pulmonary nocardiosis following COVID-19 in a patient with idiopathic pulmonary fibrosis and lung transplantation: a case report. Front Med (Lausanne) 2023; 10:1266857. [PMID: 37766921 PMCID: PMC10520695 DOI: 10.3389/fmed.2023.1266857] [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: 07/25/2023] [Accepted: 08/29/2023] [Indexed: 09/29/2023] Open
Abstract
Background Nocardiosis is an opportunistic infection that primarily affects immunocompromised patients. Pulmonary nocardiosis is the most prevalent form, but can also spread to other organs. Potential causes contributing to opportunistic infection may include immunosuppression and disruption of tight junctions, both of which can result from COVID-19. Case presentation We reported a case of a 68-year-old male patient who presented with a 10-day history of fever, cough, and productive sputum. Upon physical examination, velcro rales were detected in the right lung, while breath sounds in the left lung were clear. The patient had previously undergone left lung transplantation due to idiopathic pulmonary fibrosis four years ago. He was initially hospitalized and treated for COVID-19 but was readmitted due to worsening symptoms. Subsequently, pulmonary nocardiosis was diagnosed utilizing metagenomic next-generation sequencing of bronchoalveolar lavage fluid. The above-mentioned condition was improved following treatment with cancidas and linezolid. Now, he is under regular follow-up. Conclusion This case highlights the complexity of COVID-19 and the occurrence of secondary opportunistic infections, which require further investigation.
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Affiliation(s)
| | | | - Fei Chen
- Cancer Center, Department of Pulmonary and Critical Care Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China
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Anti-Inflammatory and/or Anti-Fibrotic Treatment of MPO-ANCA-Positive Interstitial Lung Disease: A Short Review. J Clin Med 2022; 11:jcm11133835. [PMID: 35807120 PMCID: PMC9267459 DOI: 10.3390/jcm11133835] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Revised: 06/27/2022] [Accepted: 06/30/2022] [Indexed: 11/30/2022] Open
Abstract
The presence of a lung lesion is common in microscopic polyangiitis (MPA), and interstitial lung disease (ILD) can lead to a poor prognosis. Although myeloperoxidase antineutrophil cytoplasmic antibodies (MPO-ANCA) are often present in patients with MPA, patients with ILD and MPO-ANCA positivity but without other manifestations of systemic vasculitis have also been reported. Therefore, the possible association between MPO-ANCA, MPA, and idiopathic ILD remains unclear. This problematic matter has influenced the treatment strategy of MPO-ANCA-positive ILD patients without systemic vasculitis. Clinicians should undertake treatment with careful consideration of the four major causes of death in MPO-ANCA-positive ILD: acute exacerbation of ILD, progressive lung fibrosis, infectious comorbidities, and diffuse alveolar hemorrhage. Further, clinicians need to carefully judge whether inflammation or fibrosis is the dominant condition with reference to the patient’s clinical domain and radiopathological lung features. Recently, anti-fibrotic agents such as nintedanib and pirfenidone were shown to be effective in treating various etiologies associated with ILD and have thus led to the widening of treatment options. In this review, the clinical characteristics, radiopathology, prognosis, and therapeutic options in patients with MPO-ANCA-positive ILD are summarized using limited information from previous studies.
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Park YE, Lee JH, Chong YP, Lee HJ, Kim HC, Song JW, Shim TS, Jo KW. Treatment outcomes of the interstitial lung disease subtype of unclassifiable type Mycobacterium avium complex pulmonary disease. J Infect Chemother 2022; 28:1112-1118. [DOI: 10.1016/j.jiac.2022.03.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 03/15/2022] [Accepted: 03/27/2022] [Indexed: 11/15/2022]
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Kumar K, Daley CL, Griffith DE, Loebinger MR. Management of Mycobacterium avium complex and Mycobacterium abscessus pulmonary disease: therapeutic advances and emerging treatments. Eur Respir Rev 2022; 31:210212. [PMID: 35140106 PMCID: PMC9488909 DOI: 10.1183/16000617.0212-2021] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Accepted: 12/03/2021] [Indexed: 12/14/2022] Open
Abstract
Nontuberculous mycobacterial pulmonary disease (NTM-PD) remains a challenging condition to diagnose and treat effectively. Treatment of NTM-PD is prolonged, frequently associated with adverse effects and has variable success. In this review, we consider the factors influencing clinicians when treating NTM-PD and discuss outcomes from key studies on the pharmacological management of Mycobacterium avium complex pulmonary disease and M. abscessus pulmonary disease. We highlight issues relating to treatment-related toxicity and provide an overview of repurposed and emerging therapies for NTM-PD.
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Affiliation(s)
- Kartik Kumar
- National Heart and Lung Institute, Imperial College London, London, UK
- Host Defence Unit, Dept of Respiratory Medicine, Royal Brompton Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Charles L Daley
- Division of Mycobacterial and Respiratory Infections, Dept of Medicine, National Jewish Health, Denver, CO, USA
- School of Medicine, University of Colorado, Aurora, CO, USA
| | - David E Griffith
- Division of Mycobacterial and Respiratory Infections, Dept of Medicine, National Jewish Health, Denver, CO, USA
| | - Michael R Loebinger
- National Heart and Lung Institute, Imperial College London, London, UK
- Host Defence Unit, Dept of Respiratory Medicine, Royal Brompton Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK
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12
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Kumar K, Loebinger MR. Nontuberculous Mycobacterial Pulmonary Disease: Clinical Epidemiologic Features, Risk Factors, and Diagnosis: The Nontuberculous Mycobacterial Series. Chest 2022; 161:637-646. [PMID: 34627854 DOI: 10.1016/j.chest.2021.10.003] [Citation(s) in RCA: 45] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Revised: 07/26/2021] [Accepted: 10/02/2021] [Indexed: 10/20/2022] Open
Abstract
Nontuberculous mycobacterial pulmonary disease (NTM-PD) continues to impose a significant clinical burden of disease on susceptible patients. The incidence of NTM-PD is rising globally, but it remains a condition that is challenging to diagnose and treat effectively. This review provides an update on the global epidemiologic features, risk factors, and diagnostic considerations associated with the management of NTM-PD.
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Affiliation(s)
- Kartik Kumar
- National Heart and Lung Institute, Imperial College London, London, England; Host Defence Unit, Department of Respiratory Medicine, Royal Brompton Hospital, Guy's and St Thomas' NHS Foundation Trust, London, England
| | - Michael R Loebinger
- National Heart and Lung Institute, Imperial College London, London, England; Host Defence Unit, Department of Respiratory Medicine, Royal Brompton Hospital, Guy's and St Thomas' NHS Foundation Trust, London, England.
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13
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Barua N, Buragohain AK. Therapeutic Potential of Curcumin as an Antimycobacterial Agent. Biomolecules 2021; 11:biom11091278. [PMID: 34572491 PMCID: PMC8470464 DOI: 10.3390/biom11091278] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Revised: 08/23/2021] [Accepted: 08/23/2021] [Indexed: 01/06/2023] Open
Abstract
Curcumin is the principal curcuminoid obtained from the plant Curcuma longa and has been extensively studied for its biological and chemical properties. Curcumin displays a vast range of pharmacological properties, including antimicrobial, anti-inflammatory, antioxidant, and antitumor activity. Specifically, curcumin has been linked to the improvement of the outcome of tuberculosis. There are many reviews on the pharmacological effects of curcumin; however, reviews of the antitubercular activity are comparatively scarcer. In this review, we attempt to discuss the different aspects of the research on the antitubercular activity of curcumin. These include antimycobacterial activity, modulation of the host immune response, and enhancement of BCG vaccine efficacy. Recent advances in the antimycobacterial activity of curcumin synthetic derivatives, the role of computer aided drug design in identifying curcumin targets, the hepatoprotective role of curcumin, and the dosage and toxicology of curcumin will be discussed. While growing evidence supports the use of curcumin and its derivatives for tuberculosis therapy, further preclinical and clinical investigations are of pivotal importance before recommending the use of curcumin formulations in public health.
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Affiliation(s)
- Nilakshi Barua
- Department of Molecular Biology and Biotechnology, Tezpur University, Tezpur 784028, India
- Department of Microbiology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin 999077, Hong Kong
- Correspondence: (N.B.); (A.K.B.)
| | - Alak Kumar Buragohain
- Department of Molecular Biology and Biotechnology, Tezpur University, Tezpur 784028, India
- Department of Biotechnology, Royal Global University, Guwahati 781035, India
- Correspondence: (N.B.); (A.K.B.)
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14
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The role of viral and bacterial infections in the pathogenesis of IPF: a systematic review and meta-analysis. Respir Res 2021; 22:53. [PMID: 33579274 PMCID: PMC7880524 DOI: 10.1186/s12931-021-01650-x] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2020] [Accepted: 02/04/2021] [Indexed: 02/06/2023] Open
Abstract
Background Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease. Several risk factors such as smoking, air pollution, inhaled toxins, high body mass index and infectious agents are involved in the pathogenesis of IPF. In the present study, this meta-analysis study investigates the prevalence of viral and bacterial infections in the IPF patients and any possible association between these infections with pathogenesis of IPF. Methods The authors carried out this systematic literature review from different reliable databases such as PubMed, ISI Web of Science, Scopus and Google Scholar to December 2020.Keywords used were the following “Idiopathic pulmonary fibrosis”, “Infection”, “Bacterial Infection” and “Viral Infection”, alone or combined together with the Boolean operators "OR”, “AND” and “NOT” in the Title/Abstract/Keywords field. Pooled proportion and its 95% CI were used to assess the prevalence of viral and bacterial infections in the IPF patients. Results In this systematic review and meta-analyses, 32 studies were selected based on the exclusion/inclusion criteria. Geographical distribution of included studies was: eight studies in American people, 8; in European people, 15 in Asians, and one in Africans. The pooled prevalence for viral and bacterial infections w ere 53.72% (95% CI 38.1–69.1%) and 31.21% (95% CI 19.9–43.7%), respectively. The highest and lowest prevalence of viral infections was HSV (77.7% 95% CI 38.48–99.32%), EBV (72.02%, 95% CI 44.65–90.79%) and Influenza A (7.3%, 95% CI 2.66–42.45%), respectively. Whereas the highest and lowest prevalence in bacterial infections were related to Streptococcus sp. (99.49%, 95% CI 96.44–99.9%) and Raoultella (1.2%, 95% CI 0.2–3.08%), respectively. Conclusions The results of this review were confirmed that the presence of viral and bacterial infections are the risk factors in the pathogenesis of IPF. In further analyses, which have never been shown in the previous studies, we revealed the geographic variations in the association strengths and emphasized other methodological parameters (e.g., detection method). Also, our study supports the hypothesis that respiratory infection could play a key role in the pathogenesis of IP.
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PC945, a Novel Inhaled Antifungal Agent, for the Treatment of Respiratory Fungal Infections. J Fungi (Basel) 2020; 6:jof6040373. [PMID: 33348852 PMCID: PMC7765807 DOI: 10.3390/jof6040373] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Revised: 12/02/2020] [Accepted: 12/15/2020] [Indexed: 12/25/2022] Open
Abstract
Disease due to pulmonary Aspergillus infection remains a significant unmet need, particularly in immunocompromised patients, patients in critical care and those with underlying chronic lung diseases. To date, treatment using inhaled antifungal agents has been limited to repurposing available systemic medicines. PC945 is a novel triazole antifungal agent, a potent inhibitor of CYP51, purpose-designed to be administered via inhalation for high local lung concentrations and limited systemic exposure. In preclinical testing, PC945 is potent versus Aspergillus spp. and Candida spp. and showed two remarkable properties in preclinical studies, in vitro and in vivo. The antifungal effects against Aspergillus fumigatus accumulate on repeat dosing and improved efficacy has been demonstrated when PC945 is dosed in combination with systemic anti-fungal agents of multiple classes. Resistance to PC945 has been induced in Aspergillus fumigatus in vitro, resulting in a strain which remained susceptible to other antifungal triazoles. In healthy volunteers and asthmatics, nebulised PC945 was well tolerated, with limited systemic exposure and an apparently long lung residency time. In two lung transplant patients, PC945 treated an invasive pulmonary Aspergillus infection that had been unresponsive to multiple antifungal agents (systemic ± inhaled) without systemic side effects or detected drug–drug interactions.
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