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Sunder T, Thangaraj PR, Kuppusamy MK. Venous thromboembolism following lung transplantation. World J Transplant 2025; 15:99241. [DOI: 10.5500/wjt.v15.i2.99241] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Revised: 10/12/2024] [Accepted: 11/14/2024] [Indexed: 02/21/2025] Open
Abstract
Lung transplantation (LT) is currently a surgical therapy option for end-stage lung disease. Venous thromboembolism (VTE), which can occur after LT, is associated with significant morbidity and mortality. Because of improved outcomes, increasing numbers of patients are receiving LT as treatment. Patients on the waitlist for LT tend to be older with weakness and frailty in addition to pulmonary symptoms. These factors contribute to a heightened risk of postoperative VTE. Furthermore, patients who clinically deteriorate while on the waitlist may require extra corporeal membrane oxygenation as a bridge to LT. Bleeding and thromboembolism are common in these patients. Pulmonary embolism (PE) in a freshly transplanted lung can have significant effects leading to morbidity and mortality. PE typically leads to impairment of gas exchange and right ventricular strain. In LT, PE can affect healing of bronchial anastomosis and may even contribute to the development of chronic allograft lung dysfunction. This article discussed the incidence, clinical features and diagnosis of VTE after LT. Furthermore, the treatment modalities, complications, and outcomes of VTE were reviewed.
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Affiliation(s)
- Thirugnanasambandan Sunder
- Department of Heart Lung Transplantation and Mechanical Circulatory Support, Apollo Hospitals, Chennai 600086, Tamil Nadu, India
| | - Paul Ramesh Thangaraj
- Department of Heart Lung Transplantation and Mechanical Circulatory Support, Apollo Hospitals, Chennai 600086, Tamil Nadu, India
| | - Madhan Kumar Kuppusamy
- Department of Heart Lung Transplantation and Mechanical Circulatory Support, Apollo Hospitals, Chennai 600086, Tamil Nadu, India
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Selman M, Buendia-Roldan I, Pardo A. Decoding the complexity: mechanistic insights into comorbidities in idiopathic pulmonary fibrosis. Eur Respir J 2025; 65:2402418. [PMID: 40180336 PMCID: PMC12095908 DOI: 10.1183/13993003.02418-2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2024] [Accepted: 03/12/2025] [Indexed: 04/05/2025]
Abstract
The complex pathogenic relationships between idiopathic pulmonary fibrosis (IPF) and its usually associated comorbidities remain poorly understood. While evidence suggests that some comorbidities may directly influence the development or progression of IPF, or vice versa, whether these associations are causal or arise independently due to shared risk factors, such as ageing, smoking, lifestyle and genetic susceptibility, is still uncertain. Some comorbidities, such as metabolic syndromes, gastro-oesophageal reflux disease and obstructive sleep apnoea, precede the development of IPF. In contrast, others, such as pulmonary hypertension and lung cancer, often become apparent after IPF onset or during its progression. These timing patterns suggest a directional relationship in their associations. The issue is further complicated by the fact that patients often have multiple comorbidities, which may interact and exacerbate one another, creating a vicious cycle. To clarify these correlations, some studies have used causal inference methods (e.g. Mendelian randomisation) and exploration of underlying mechanisms; however, these efforts have not yet generated conclusive insights. In this review, we provide a general overview of the relationship between IPF and its comorbidities, emphasising the pathogenic mechanisms underlying each comorbidity, potential shared pathobiology with IPF and, when available, causal insights from Mendelian randomisation studies.
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Affiliation(s)
- Moisés Selman
- Instituto Nacional de Enfermedades Respiratorias "Ismael Cosío Villegas", Mexico City, Mexico
| | - Ivette Buendia-Roldan
- Instituto Nacional de Enfermedades Respiratorias "Ismael Cosío Villegas", Mexico City, Mexico
| | - Annie Pardo
- Facultad de Ciencias, Universidad Nacional Autónoma de México, Mexico City, Mexico
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Ronan NJ, Helly F, Murray MA. Lung transplantation for interstitial lung disease. Breathe (Sheff) 2025; 21:240169. [PMID: 40365094 PMCID: PMC12070198 DOI: 10.1183/20734735.0169-2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2024] [Accepted: 01/21/2025] [Indexed: 05/15/2025] Open
Abstract
Interstitial lung diseases (ILDs) are now the most common indication for lung transplant internationally. Given that many lung transplant candidates with idiopathic pulmonary fibrosis are older, referral to a pulmonary rehabilitation programme is important to help mitigate the adverse outcomes associated with frailty. Despite this increase many patients with ILD who would potentially benefit from lung transplant are either not referred or referred too late. Particularly relevant in ILD which may have prominent extra-pulmonary manifestations is a multidisciplinary assessment of comorbidities which may impact on post lung transplant outcomes. Particular challenges in lung transplant for ILD are increasing age, comorbidities, donor lung sizing and the risk-benefit balance of single versus bilateral lung transplant. Evidence is continuing to evolve for lung transplant in rarer ILDs, including surfactant protein associated ILD and TERT mutations. Unfortunately, the number of potential lung transplant recipients exceeds available donor organs and some patients will die without transplant. Palliative care is an important aspect of managing patients on an active lung transplant list to help optimise physical and psychological symptoms associated with uncertainty on an active lung transplant list.
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Affiliation(s)
- Nicola J. Ronan
- National Heart and Lung Transplant Unit, Mater Misericordiae University Hospital, Dublin, Ireland
- School of Medicine, University College Dublin, Dublin, Ireland
| | - Feargal Helly
- National Heart and Lung Transplant Unit, Mater Misericordiae University Hospital, Dublin, Ireland
| | - Michelle A. Murray
- National Heart and Lung Transplant Unit, Mater Misericordiae University Hospital, Dublin, Ireland
- School of Medicine, University College Dublin, Dublin, Ireland
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Kette S, Reccardini N, Salton F, Confalonieri P, Andrisano A, Chianese M, De Nes A, Maggisano M, Galantino A, Nicolosi S, Mari M, Salotti A, Angoni D, Chernovsky M, Hughes M, Confalonieri M, Mondini L, Ruaro B. The Impact of Comorbidities on the Discontinuation of Antifibrotic Therapy in Patients with Idiopathic Pulmonary Fibrosis. Pharmaceuticals (Basel) 2025; 18:411. [PMID: 40143187 PMCID: PMC11944575 DOI: 10.3390/ph18030411] [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: 01/22/2025] [Revised: 03/02/2025] [Accepted: 03/12/2025] [Indexed: 03/28/2025] Open
Abstract
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease of unknown aetiology. Evidence on the progression of idiopathic pulmonary fibrosis (IPF) following the introduction of antifibrotic therapies still indicates a generally poor prognosis. IPF is associated with both respiratory and non-respiratory comorbidities, which can worsen symptoms and impact overall survival. Background/Objectives: The study aimed to investigate the effect of these comorbidities on the early and permanent discontinuation of pirfenidone or nintedanib in IPF patients. Methods: In this single-centre retrospective study, 101 patients diagnosed with IPF according to ATS/ERS/JRS/ALAT guidelines were treated with AFT. Clinical data were collected at 12 months prior to and up to 24 months following treatment initiation, including age, gender, smoking history, and the presence of respiratory and non-respiratory comorbidities. Results: The data showed that 21 patients (20.8%) discontinued treatment within the first 12 months. Additionally, pre-treatment comorbidities were not statistically correlated with the suspension of antifibrotic treatment. Among the overall cohort, 77 patients (76.2%) had at least one comorbidity and 27 (26.7%) had three or more comorbidities. Notably, 24 (23.8%) had respiratory comorbidities, while 75 (74.3%) had non-respiratory comorbidities. Conclusions: This real-life study emphasises the complexities involved in managing IPF, particularly regarding adherence to treatment when significant comorbidities are present. The evidence suggests that in patients with IPF, pre-treatment respiratory or non-respiratory conditions do not affect AFT discontinuation.
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Affiliation(s)
- Stefano Kette
- Pulmonology Unit, Department of Medical Surgical and Health Sciences, University of Trieste, Hospital of Cattinara, 34149 Trieste, Italy
| | - Nicolò Reccardini
- Pulmonology Unit, Department of Medical Surgical and Health Sciences, University of Trieste, Hospital of Cattinara, 34149 Trieste, Italy
| | - Francesco Salton
- Pulmonology Unit, Department of Medical Surgical and Health Sciences, University of Trieste, Hospital of Cattinara, 34149 Trieste, Italy
| | - Paola Confalonieri
- Pulmonology Unit, Department of Medical Surgical and Health Sciences, University of Trieste, Hospital of Cattinara, 34149 Trieste, Italy
| | - Alessia Andrisano
- Pulmonology Unit, Department of Cardio-Thoracic Surgery, Health Integrated Agency of Friuli Venezia Giulia, 33100 Udine, Italy
| | - Maria Chianese
- Pulmonology Unit, Department of Medical Surgical and Health Sciences, University of Trieste, Hospital of Cattinara, 34149 Trieste, Italy
| | - Anna De Nes
- Pulmonology Unit, Department of Medical Surgical and Health Sciences, University of Trieste, Hospital of Cattinara, 34149 Trieste, Italy
| | - Marta Maggisano
- Pulmonology Unit, Department of Medical Surgical and Health Sciences, University of Trieste, Hospital of Cattinara, 34149 Trieste, Italy
| | - Alessandra Galantino
- Pulmonology Unit, Department of Medical Surgical and Health Sciences, University of Trieste, Hospital of Cattinara, 34149 Trieste, Italy
| | - Salvatore Nicolosi
- Pulmonology Unit, Department of Medical Surgical and Health Sciences, University of Trieste, Hospital of Cattinara, 34149 Trieste, Italy
| | - Marco Mari
- Pulmonology Unit, Department of Medical Surgical and Health Sciences, University of Trieste, Hospital of Cattinara, 34149 Trieste, Italy
| | - Andrea Salotti
- Pulmonology Unit, Department of Medical Surgical and Health Sciences, University of Trieste, Hospital of Cattinara, 34149 Trieste, Italy
| | - Darina Angoni
- Pulmonology Unit, Department of Medical Surgical and Health Sciences, University of Trieste, Hospital of Cattinara, 34149 Trieste, Italy
| | - Maria Chernovsky
- Pulmonology Unit, Department of Medical Surgical and Health Sciences, University of Trieste, Hospital of Cattinara, 34149 Trieste, Italy
| | - Michael Hughes
- Division of Musculoskeletal and Dermatological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester & Salford Royal NHS Foundation Trust, Manchester M6 8HD, UK
| | - Marco Confalonieri
- Pulmonology Unit, Department of Medical Surgical and Health Sciences, University of Trieste, Hospital of Cattinara, 34149 Trieste, Italy
| | - Lucrezia Mondini
- Pulmonology Unit, Department of Medical Surgical and Health Sciences, University of Trieste, Hospital of Cattinara, 34149 Trieste, Italy
| | - Barbara Ruaro
- Pulmonology Unit, Department of Medical Surgical and Health Sciences, University of Trieste, Hospital of Cattinara, 34149 Trieste, Italy
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Kwak HS, Kim HC, Koo HJ, Lee SW, Lee PH, Kim TO. Incidence and clinical impact of coronary artery disease confirmed by coronary CT angiography in patients with interstitial lung disease. BMC Pulm Med 2025; 25:88. [PMID: 39987066 PMCID: PMC11847390 DOI: 10.1186/s12890-025-03554-8] [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: 12/02/2024] [Accepted: 02/11/2025] [Indexed: 02/24/2025] Open
Abstract
BACKGROUND Patients with interstitial lung disease (ILD) who undergo routine chest computed tomography (CT) often have findings suggestive of coronary artery disease (CAD). However, the incidence and prognostic impact of significant CAD, confirmed by coronary CT angiography (CCTA), are not well established. METHODS From January 2013 to February 2024, we evaluated 215 patients from a retrospective ILD registry at our institute, who underwent CCTA as part of ILD management. Using the CAD-Reporting and Data System, we investigated the incidence of significant CAD and evaluated its impact on 5-year mortality and rehospitalization for respiratory or cardiovascular causes through multivariable Cox proportional hazards regression. RESULTS During a median follow-up of 2.3 years, CCTA was performed at a median of 5 months postdiagnosis of ILD in the cohort. Significant CAD was identified in 92 patients (42.8%), with 27 (12.6%) undergoing coronary revascularization. The presence of significant CAD was significantly associated with an increased risk of mortality (adjusted hazard ratio [HR]: 2.31; 95% confidence interval [CI]: 1.07 - 5.01; P = 0.03) and a higher risk of rehospitalization (adjusted HR: 2.03; 95% CI: 1.23 - 3.34; P = 0.01). Key clinical variables associated with significant CAD included older age (≥ 63 years), hypertension, and coronary calcification observed on non-gated chest CT. CONCLUSIONS CCTA-identified CAD was associated with a worse clinical prognosis in patients with ILD, with significant risk factors including older age, hypertension, and coronary calcification observed on non-gated chest CT. These findings suggest that obtaining CCTA may be beneficial for managing patients with ILD, particularly those with identified risk factors.
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Affiliation(s)
- Hyun Seok Kwak
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Ho Cheol Kim
- Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Hyun Jung Koo
- Department of Radiology and Research Institute of Radiology, Cardiac Imaging Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Seung-Whan Lee
- Division of Cardiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, Republic of Korea
| | - Pil Hyung Lee
- Division of Cardiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, Republic of Korea
| | - Tae Oh Kim
- Division of Cardiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, Republic of Korea.
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Fahim A, Loughenbury M, Stewart I, Agnew S, Almond H, Casimo L, Chaudhuri N, Fletcher SV, Haney S, Ho LP, Hodkinson C, Minnis P, Palmer E, Wilson AM. Idiopathic pulmonary fibrosis in the UK: findings from the British Thoracic Society UK Idiopathic Pulmonary Fibrosis Registry. BMJ Open Respir Res 2025; 12:e002773. [PMID: 39971593 PMCID: PMC11840905 DOI: 10.1136/bmjresp-2024-002773] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Accepted: 01/07/2025] [Indexed: 02/21/2025] Open
Abstract
OBJECTIVES Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease (ILD) and the most common idiopathic interstitial pneumonia. The UK IPF Registry was established in 2013 to collect data pertaining to clinical features, therapeutic approaches and outcomes. From February 2023, the Registry expanded to include any ILD with evidence of fibrosis. DESIGN The UK IPF Registry is a national, multicentre observational registry, including both prospective and retrospective data of patients with IPF in secondary or tertiary care. Cases eligible for inclusion were those with a diagnosis of IPF, presenting at participating centres from January 2013. RESULTS Between January 2013 and February 2023, 5052 IPF cases were registered from 64 participating centres. There was a male preponderance (77.8%) with mean±SD age of 74±8.1 years, 66% were ex-smokers and 76% had at least one comorbidity. Over a third (36.7%) experienced symptoms for more than 24 months prior to their first clinic visit. The majority of cases were discussed at a multidisciplinary team (MDT) meeting and the most common radiological patterns at presentation were probable (54.6%) and definite (42.7%) usual interstitial pneumonia. There was a reduction in surgical lung biopsies from 14% in 2013 to 5.5% in 2022. Antifibrotic therapy prescription rose from 36.0% in 2013 to 55.9% in 2023. The use of nintedanib (approved by National Institute of Clinical Excellence in January 2016) rose from 6.7% in 2013 to 31.5% in 2022 and pirfenidone (approved in April 2013) was initially used in around a third of cases before dropping to between 16.8% and 24.9% after nintedanib was approved. CONCLUSION These data reflect clinical practice across the UK and it is intended the data will have a role in informing the future of IPF care and providing a model for benchmarking, ultimately increasing knowledge and improving clinical care for this devastating disease.
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Affiliation(s)
- Ahmed Fahim
- New Cross Hospital, The Royal Wolverhampton NHS Trust, Wolverhampton, UK
| | | | - Iain Stewart
- National Heart and Lung Institute, NIHR Imperial Biomedical Research Centre, Imperial College London, London, UK
| | - Sarah Agnew
- Liverpool Interstitial Lung Disease Service, Aintree Hospital, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | | | | | - Nazia Chaudhuri
- School of Medicine, Department of Life and Health Sciences, Ulster University, Northern Ireland, UK
| | - Sophie V Fletcher
- University Hospital of Southampton NHS Foundation Trust, Southampton, UK
- NIHR Southampton Respiratory Biomedical Research Centre and School of Clinical and Experimental Sciences, Faulty of Medicine, University of Southampton, Southampton, UK
| | - Sarah Haney
- Northumbria Healthcare NHS Foundation Trust, Ashington, UK
| | - Ling-Pei Ho
- MRC Translational Immune Discovery Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK
- NIHR Oxford Biomedical Research Centre, Oxford, UK
| | | | - Paul Minnis
- Antrim Area Hospital, Northern Health and Social Care Trust, Antrim, UK
| | - Evelyn Palmer
- Royal Victoria Infirmary, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Andrew M Wilson
- Norwich Medical School, University of East Anglia, Norwich, UK
- Norfolk and Norwich University Hospital, NHS Foundation Trust, Norwich, UK
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Sonaglioni A, Caminati A, Nicolosi GL, Muti-Schünemann GEU, Lombardo M, Harari S. Echocardiographic Assessment of Biventricular Mechanics in Patients with Mild-to-Moderate Idiopathic Pulmonary Fibrosis: A Systematic Review and Meta-Analysis. J Clin Med 2025; 14:714. [PMID: 39941384 PMCID: PMC11818070 DOI: 10.3390/jcm14030714] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2024] [Revised: 01/18/2025] [Accepted: 01/21/2025] [Indexed: 02/16/2025] Open
Abstract
Background: Over the last few years, a few imaging studies have performed conventional transthoracic echocardiography (TTE) implemented with speckle tracking echocardiography (STE) for the assessment of biventricular mechanics in patients with non-advanced idiopathic pulmonary fibrosis (IPF). This systematic review and meta-analysis aimed at evaluating the overall effect of mild-to-moderate IPF on the main indices of biventricular systolic function assessed by TTE and STE. Methods: All imaging studies assessing right ventricular (RV)-global longitudinal strain (GLS), left ventricular (LV)-GLS, tricuspid annular plane systolic excursion (TAPSE), and left ventricular ejection fraction (LVEF) in IPF patients vs. healthy controls, selected from PubMed, Scopus, and EMBASE databases, were included. Continuous data (RV-GLS, LV-GLS, TAPSE, and LVEF) were pooled as standardized mean differences (SMDs) comparing the IPF group with healthy controls. The SMD of RV-GLS was calculated using the random-effect model, whereas the SMDs of LV-GLS, TAPSE, and LVEF were calculated using the fixed-effect model. Results: The full texts of 6 studies with 255 IPF patients and 195 healthy controls were analyzed. Despite preserved TAPSE and LVEF, both RV-GLS and LV-GLS were significantly, although modestly, reduced in the IPF patients vs. the controls. The SMD was large (-1.01, 95% CI -1.47, -0.54, p < 0.001) for RV-GLS, medium (-0.62, 95% CI -0.82, -0.42, p < 0.001) for LV-GLS, small (-0.42, 95% CI -0.61, -0.23, p < 0.001) for TAPSE, and small and not statistically significant (-0.20, 95% CI -0.42, 0.03, p = 0.09) for LVEF assessment. Between-study heterogeneity was high for the studies assessing RV-GLS (I2 = 80.5%), low-to-moderate for those evaluating LV-GLS (I2 = 41.7%), and low for those measuring TAPSE (I2 = 16.4%) and LVEF (I2 = 7.63%). The Egger's test yielded a p-value of 0.60, 0.11, 0.31, and 0.68 for the RV-GLS, LV-GLS, TAPSE, and LVEF assessment, respectively, indicating no publication bias. On meta-regression analysis, none of the moderators was significantly associated with effect modification for RV-GLS (all p > 0.05). The sensitivity analysis supported the robustness of the results. Conclusions: RV-GLS impairment is an early marker of subclinical myocardial dysfunction in mild-to-moderate IPF. STE should be considered for implementation in clinical practice for early detection of RV dysfunction in IPF patients without advanced lung disease.
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Affiliation(s)
| | - Antonella Caminati
- Semi-Intensive Care Unit, Division of Pneumology, IRCCS MultiMedica, 20123 Milan, Italy; (A.C.); (S.H.)
| | | | | | | | - Sergio Harari
- Semi-Intensive Care Unit, Division of Pneumology, IRCCS MultiMedica, 20123 Milan, Italy; (A.C.); (S.H.)
- Department of Clinical Sciences and Community Health, Università di Milano, 20122 Milan, Italy
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León-Román F, Pintado-Cort B, Barberà JA, Sellares J, Iturbe D, López-Zubizarreta M, Peña-Miguel T, Durán-Barata D, Jiménez D. [Diagnosis and Treatment of Pulmonary Embolism and Pulmonary Hypertension in Patients With Interstitial Lung Disease]. OPEN RESPIRATORY ARCHIVES 2025; 7:100406. [PMID: 40104013 PMCID: PMC11915155 DOI: 10.1016/j.opresp.2025.100406] [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: 09/30/2024] [Accepted: 01/20/2025] [Indexed: 03/20/2025] Open
Abstract
Pulmonary embolism (PE) and pulmonary hypertension (PH) are common comorbidities that worsen the prognosis of patients diagnosed with interstitial lung disease (ILD). Despite advances in the diagnosis and treatment of these entities, their impact on the management and progression of ILD is not sufficiently studied. This article includes a review and update of the diagnosis and treatment of PE and PH in patients with underlying ILD.
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Affiliation(s)
- Francisco León-Román
- Servicio de Neumología, Hospital Recoletas Salud Campo Grande, Valladolid, España
| | - Beatriz Pintado-Cort
- Servicio de Neumología, Hospital Recoletas Salud Campo Grande, Valladolid, España
| | - Joan Albert Barberà
- Servicio de Neumología, Hospital Clinic, Barcelona, España
- CIBER Enfermedades Respiratorias (CIBERES), Madrid, España
| | | | - David Iturbe
- Servicio de Neumología, Hospital Marqués de Valdecilla, Santander, España
| | | | - Teresa Peña-Miguel
- Servicio de Neumología, Hospital Universitario de Burgos, Burgos, España
| | - Diego Durán-Barata
- Servicio de Neumología, Hospital Universitario de Getafe, Getafe, Madrid, España
- Departamento de Medicina, Universidad de Alcalá, Madrid, España
| | - David Jiménez
- CIBER Enfermedades Respiratorias (CIBERES), Madrid, España
- Departamento de Medicina, Universidad de Alcalá, Madrid, España
- Servicio de Neumología, Hospital Ramón y Cajal e Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, España
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9
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Wu P, Zhang W, Zuo X, Liu S, Jin T, Jia J, Luo B, Wang G, Zhang Z. The hematopoietic activity of EPO is unfavorable to the treatment of bleomycin-induced pulmonary fibrosis in mice. Biochem Biophys Res Commun 2024; 739:150951. [PMID: 39547119 DOI: 10.1016/j.bbrc.2024.150951] [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: 10/19/2024] [Revised: 10/22/2024] [Accepted: 11/03/2024] [Indexed: 11/17/2024]
Abstract
The main function of erythropoietin (EPO) is to promote hematopoiesis and improve anemia. In addition, EPO also has many non-hematopoietic effects such as anti-inflammation, anti-apoptosis and anti-oxidation. To achieve the protective effects, large doses of EPO are required, so the probability of side effects increases. Previous studies have revealed that EPO can improve pulmonary fibrosis in mice, but it has not been clarified whether the hematopoiesis of EPO contributes to amelioration of pulmonary fibrosis and whether EPO improves overall mortality. Our results show that EPO decreases hydroxyproline content, α-sma and col-1 protein levels in mice with bleomycin-induced pulmonary fibrosis. However, compared with the control group, the weight loss and mortality rate of the EPO group were not improved, while the number of red blood cells (RBCs), hemoglobin (Hb), red cell width distribution-coefficient of variation (RDW-CV) and hematocrit (HCT) were significantly higher. Furthermore, we observed massive thrombosis in the lung of EPO treated lung fibrosis mice but not in control mice. Therefore, our results show that in the condition of lung fibrosis, the hematopoietic activity of exogenous EPO is not conducive to its tissue protective effect.
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Affiliation(s)
- Pengfei Wu
- Department of Pulmonary and Critical Care Medicine, Institute of Respiratory Diseases, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing, China; Department of Respiratory and Critical Care Medicine, Sichuan Science City Hospital, Mianyang, Sichuan, China
| | - Wen Zhang
- Department of Pulmonary and Critical Care Medicine, Institute of Respiratory Diseases, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Xitong Zuo
- Institute of Immunology, Third Military Medical University, Chongqing, China
| | - Shengran Liu
- Institute of Immunology, Third Military Medical University, Chongqing, China
| | - Tianrong Jin
- Medical College of Chongqing University, Chongqing, China
| | - Jialin Jia
- Institute of Immunology, Third Military Medical University, Chongqing, China
| | - Bangwei Luo
- Institute of Immunology, Third Military Medical University, Chongqing, China.
| | - Guansong Wang
- Department of Pulmonary and Critical Care Medicine, Institute of Respiratory Diseases, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
| | - Zhiren Zhang
- Institute of Immunology, Third Military Medical University, Chongqing, China.
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10
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Cenerini G, Chimera D, Pagnini M, Bazzan E, Conti M, Turato G, Celi A, Neri T. The Intricate Relationship Between Pulmonary Fibrosis and Thrombotic Pathology: A Narrative Review. Cells 2024; 13:2099. [PMID: 39768190 PMCID: PMC11674501 DOI: 10.3390/cells13242099] [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: 10/31/2024] [Revised: 12/16/2024] [Accepted: 12/17/2024] [Indexed: 01/11/2025] Open
Abstract
Idiopathic pulmonary fibrosis (IPF) is associated with a significantly increased risk of thrombotic events and mortality. This review explores the complex bidirectional relationship between pulmonary fibrosis and thrombosis, discussing epidemiological evidence, pathogenetic mechanisms, and therapeutic implications, with a particular focus on the emerging role of extracellular vesicles (EVs) as crucial mediators linking fibrosis and coagulation. Coagulation factors directly promote fibrosis, while fibrosis itself activates thrombotic pathways. Retrospective studies suggest the benefits of anticoagulants in IPF, but prospective trials have faced challenges. Novel anticoagulants, profibrinolytic therapies, and agents targeting protease-activated receptors (PARs) show promise in preclinical studies and early clinical trials. EVs have emerged as key players in the pathogenesis of interstitial lung diseases (ILDs), serving as vehicles for intercellular communication and contributing to both fibrosis and coagulation. EV-based approaches, such as EV modulation, engineered EVs as drug delivery vehicles, and mesenchymal stem cell-derived EVs, represent promising therapeutic strategies. Ongoing research should focus on optimizing risk-benefit profiles, identifying predictive biomarkers, evaluating combination strategies targeting thrombotic, fibrotic, and inflammatory pathways, and advancing the understanding of EVs in ILDs to develop targeted interventions.
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Affiliation(s)
- Giovanni Cenerini
- UO Pneumologia, Azienda Ospedaliero-Universitaria Pisana, 56124 Pisa, Italy; (G.C.); (D.C.)
| | - Davide Chimera
- UO Pneumologia, Azienda Ospedaliero-Universitaria Pisana, 56124 Pisa, Italy; (G.C.); (D.C.)
| | - Marta Pagnini
- Centro Dipartimentale di Biologia Cellulare Cardiorespiratoria, Dipartimento di Patologia Chirurgica, Medica, Molecolare e dell’Area Critica, Università degli Studi di Pisa, 56124 Pisa, Italy; (M.P.); (T.N.)
| | - Erica Bazzan
- Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova and Padova City Hospital, 35128 Padova, Italy; (E.B.); (M.C.); (G.T.)
| | - Maria Conti
- Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova and Padova City Hospital, 35128 Padova, Italy; (E.B.); (M.C.); (G.T.)
- Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy
| | - Graziella Turato
- Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova and Padova City Hospital, 35128 Padova, Italy; (E.B.); (M.C.); (G.T.)
| | - Alessandro Celi
- Centro Dipartimentale di Biologia Cellulare Cardiorespiratoria, Dipartimento di Patologia Chirurgica, Medica, Molecolare e dell’Area Critica, Università degli Studi di Pisa, 56124 Pisa, Italy; (M.P.); (T.N.)
| | - Tommaso Neri
- Centro Dipartimentale di Biologia Cellulare Cardiorespiratoria, Dipartimento di Patologia Chirurgica, Medica, Molecolare e dell’Area Critica, Università degli Studi di Pisa, 56124 Pisa, Italy; (M.P.); (T.N.)
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11
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Sinha R, Nanavaty D, Azhar A, Devarakonda P, Singh S, Garikipati R, Sanghvi A, Manoharan S, Parhar G, Zaman K, Ayala-Rodriguez C, Vasudevan V, Reddy S, Gerolemou L. A Step towards understanding coronary artery disease: a complication in idiopathic pulmonary fibrosis. BMJ Open Respir Res 2024; 11:e001834. [PMID: 38508700 PMCID: PMC10961575 DOI: 10.1136/bmjresp-2023-001834] [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: 05/18/2023] [Accepted: 02/09/2024] [Indexed: 03/22/2024] Open
Abstract
BACKGROUND Idiopathic pulmonary fibrosis (IPF) is a relatively rare disease with increasing incidence trends. Cardiovascular disease is a significant complication in IPF patients due to the role of common proatherogenic immune mediators. The prevalence of coronary artery disease (CAD) in IPF and the association between these distinct pathologies with overlapping pathophysiology remain less studied. RESEARCH QUESTION We hypothesised that IPF is an independent risk factor for CAD. METHODS We conducted a retrospective case-control study using the national inpatient sample (2017-2019). We included adult hospitalisations with IPF after excluding other interstitial lung diseases and other endpoints of CAD, acute coronary syndrome and old myocardial infarction. We examined their baseline characteristics, such as demographic data, hospital characteristics and socioeconomic status. The prevalence of cardiac risk factors and CAD was also compared between hospitalisations with and without IPF. Univariate and multivariate regression analysis was further performed to study the odds of CAD with IPF. The cases of IPF in the study population were propensity-matched, after which generalised linear modelling analysis was performed to validate the findings. RESULTS A total of 116 010 admissions were hospitalised in 2017-2019 with IPF, of which 55.6% were men with a mean age of 73 years. Adult hospitalisations with IPF were found to have a higher prevalence of diabetes mellitus (29.3% vs 24.0%; p<0.001), hypertension (35.6% vs 33.8%; p<0.001), hyperlipidaemia (47.7% vs 30.2%; p<0.0001) and tobacco abuse (41.7% vs 20.9%; p<0.001), while they had a lower prevalence of obesity (11.7% vs 15.3%; p<0.0001) compared with hospitalisations without IPF. Multivariate logistic regression analysis revealed 28% higher odds of developing CAD in IPF hospitalisations (OR -1.28; CI 1.22 to 1.33; p<0.001). Postpropensity matching, generalised linear modelling analysis revealed even higher odds of CAD with IPF (OR -1.77; CI 1.54 to 2.02; p<0.001) CONCLUSIONS: Our study found a higher prevalence of CAD in IPF hospitalisations and significantly higher odds of CAD among IPF cases. IPF remains a terminal lung disease that portends a poor prognosis, but addressing the cardiovascular risk factors in these patients can help reduce the case fatality rate due to the latter and potentially add to quality-adjusted life years.
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Affiliation(s)
- Rishav Sinha
- Internal Medicine, Brooklyn Hospital Center, Brooklyn, New York, USA
| | - Dhairya Nanavaty
- Internal Medicine, Brooklyn Hospital Center, Brooklyn, New York, USA
| | - Arij Azhar
- Pulmonary/Critical Care Medicine, Brooklyn Hospital Center, Brooklyn, New York, USA
| | | | - Sohrab Singh
- Cardiology, Brooklyn Hospital Center, Brooklyn, New York, USA
| | - Rupa Garikipati
- Pediatrics, Cooper University Health Care, Camden, New Jersey, USA
| | - Ankushi Sanghvi
- Internal Medicine, Saint Vincent Hospital, Worcester, Massachusetts, USA
| | | | - Gaurav Parhar
- Pulmonary/Critical Care Medicine, Brooklyn Hospital Center, Brooklyn, New York, USA
| | - Kiran Zaman
- Pulmonary/Critical Care Medicine, Brooklyn Hospital Center, Brooklyn, New York, USA
| | | | | | - Sarath Reddy
- Cardiology, Brooklyn Hospital Center, Brooklyn, New York, USA
| | - Louis Gerolemou
- Pulmonary/Critical Care Medicine, Brooklyn Hospital Center, Brooklyn, New York, USA
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12
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Caminati A, Zompatori M, Fuccillo N, Sonaglioni A, Elia D, Cassandro R, Trevisan R, Rispoli A, Pelosi G, Harari S. Coronary artery calcium score is a prognostic factor for mortality in idiopathic pulmonary fibrosis. Minerva Med 2023; 114:815-824. [PMID: 35671002 DOI: 10.23736/s0026-4806.22.08018-1] [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: 11/08/2022]
Abstract
BACKGROUND Cardiovascular diseases are frequent in idiopathic pulmonary fibrosis (IPF) and impact on survival. We investigated the association of coronary artery calcium (CAC) score at IPF diagnosis and during mid-term follow-up, with adverse cardiovascular events and all-cause mortality. METHODS Consecutive patients with IPF were retrospectively analyzed. Demographic data, smoking history, comorbidities and pulmonary function tests (PFTs) were recorded. All patients had at least two chest high resolution computed tomography (HRCT) performed 2 years apart. The total CAC score and visual fibrotic score were calculated, and all clinically significant cardiovascular events and deaths were reported. RESULTS The population consisted of 79 patients (57 males, mean age: 74.4±7.6 years); 67% of patients had a history of smoking, 48% of hypertension, 37% of dyslipidemia and 22.8% of diabetes. The visual score was 21.28±7.99% at T0 and 26.54±9.34% at T1, respectively (T1-T0 5.26±6.13%, P<0.001). CAC score at T0 and at T1 was 537.93±839.94 and 759.98±1027.6, respectively (T1-T0 224.66±406.87, P<0.001). Mean follow-up time was 2.47±1.1 years. On multivariate analysis, male sex (HR=3.58, 95% CI: 1.14-11.2) and CAC score at T0 (HR=1.04, 95% CI: 1.01-1.07) correlated with mortality and cardiovascular events. CAC score at T0≥405 showed 82% sensitivity and 100% specificity for predicting mortality and adverse cardiovascular events. CONCLUSIONS IPF patients with a CAC score at diagnosis ≥405 have a poor prognosis over a mid-term follow-up. A higher CAC score is associated with mortality and cardiovascular events.
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Affiliation(s)
- Antonella Caminati
- Unit of Pneumology and Semi-Intensive Respiratory Therapy, Section of Respiratory Pathophysiology and Pulmonary Hemodynamics, IRCCS MultiMedica, Milan, Italy -
| | - Maurizio Zompatori
- Department of Diagnostic Imaging, IRCCS MultiMedica, Milan, Italy
- DIMES Department, University of Bologna, Bologna, Italy
| | - Nicoletta Fuccillo
- Unit of Pneumology and Semi-Intensive Respiratory Therapy, Section of Respiratory Pathophysiology and Pulmonary Hemodynamics, IRCCS MultiMedica, Milan, Italy
| | | | - Davide Elia
- Unit of Pneumology and Semi-Intensive Respiratory Therapy, Section of Respiratory Pathophysiology and Pulmonary Hemodynamics, IRCCS MultiMedica, Milan, Italy
| | - Roberto Cassandro
- Unit of Pneumology and Semi-Intensive Respiratory Therapy, Section of Respiratory Pathophysiology and Pulmonary Hemodynamics, IRCCS MultiMedica, Milan, Italy
| | - Roberta Trevisan
- Department of Diagnostic Imaging, IRCCS MultiMedica, Milan, Italy
| | - Anna Rispoli
- Department of Diagnostic Imaging, IRCCS MultiMedica, Milan, Italy
| | - Giuseppe Pelosi
- Intercompany Service of Pathological Anatomy, Scientific and Technological Pole, IRCCS MultiMedica, Milan, Italy
| | - Sergio Harari
- Unit of Pneumology and Semi-Intensive Respiratory Therapy, Section of Respiratory Pathophysiology and Pulmonary Hemodynamics, IRCCS MultiMedica, Milan, Italy
- Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
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13
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Sonaglioni A, Caminati A, Elia D, Trevisan R, Zompatori M, Grasso E, Lombardo M, Harari S. Comparison of clinical scoring to predict mortality risk in mild-to-moderate idiopathic pulmonary fibrosis. Minerva Med 2023; 114:608-619. [PMID: 37204783 DOI: 10.23736/s0026-4806.23.08585-3] [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: 05/20/2023]
Abstract
BACKGROUND During the last decade, a number of clinical scores, such as Gender-Age-Physiology (GAP) Index, TORVAN Score and Charlson Comorbidity Index (CCI), have been separately used to measure comorbidity burden in idiopathic pulmonary fibrosis (IPF). However, no previous study compared the prognostic value of these scores to assess mortality risk stratification in IPF patients with mild-to-moderate disease. METHODS All consecutive patients with mild-to-moderate IPF who underwent high-resolution computed tomography, spirometry, transthoracic echocardiography and carotid ultrasonography at our Institution, between January 2016 and December 2018, were retrospectively analyzed. GAP Index, TORVAN Score and CCI were calculated in all patients. Primary endpoint was all-cause mortality, whereas secondary endpoint was the composite of all-cause mortality and rehospitalizations for all-causes, over medium-term follow-up. RESULTS Seventy IPF patients (70.2±7.4 yrs, 74.3% males) were examined. At baseline, GAP Index, TORVAN Score and CCI were 3.4±1.1, 14.7±4.1 and 5.3±2.4, respectively. A strong correlation between coronary artery calcification (CAC) and common carotid artery (CCA) intima-media thickness (IMT) (r=0.88), CCI and CAC (r=0.80), CCI and CCA-IMT (r=0.81), was demonstrated in the study group. Follow-up period was 3.5±1.2 years. During follow-up, 19 patients died and 32 rehospitalizations were detected. CCI (HR 2.39, 95% CI: 1.31-4.35) and heart rate (HR 1.10, 95% CI: 1.04-1.17) were independently associated with primary endpoint. CCI (HR 1.54, 95% CI: 1.15-2.06) predicted secondary endpoint, also. A CCI ≥6 was the optimal cut-off for predicting both outcomes. CONCLUSIONS Due to the increased atherosclerotic and comorbidity burden, IPF patients with CCI ≥6 at an early-stage disease have poor outcome over medium-term follow-up.
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Affiliation(s)
| | - Antonella Caminati
- Semi-Intensive Care Unit, Division of Pneumology, MultiMedica IRCCS, Milan, Italy -
| | - Davide Elia
- Semi-Intensive Care Unit, Division of Pneumology, MultiMedica IRCCS, Milan, Italy
| | | | | | - Enzo Grasso
- Division of Cardiology, MultiMedica IRCCS, Milan, Italy
| | | | - Sergio Harari
- Semi-Intensive Care Unit, Division of Pneumology, MultiMedica IRCCS, Milan, Italy
- Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
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14
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May J, Mitchell JA, Jenkins RG. Beyond epithelial damage: vascular and endothelial contributions to idiopathic pulmonary fibrosis. J Clin Invest 2023; 133:e172058. [PMID: 37712420 PMCID: PMC10503802 DOI: 10.1172/jci172058] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/16/2023] Open
Abstract
Idiopathic pulmonary fibrosis (IPF) is a progressive scarring disease of the lung with poor survival. The incidence and mortality of IPF are rising, but treatment remains limited. Currently, two drugs can slow the scarring process but often at the expense of intolerable side effects, and without substantially changing overall survival. A better understanding of mechanisms underlying IPF is likely to lead to improved therapies. The current paradigm proposes that repetitive alveolar epithelial injury from noxious stimuli in a genetically primed individual is followed by abnormal wound healing, including aberrant activity of extracellular matrix-secreting cells, with resultant tissue fibrosis and parenchymal damage. However, this may underplay the importance of the vascular contribution to fibrogenesis. The lungs receive 100% of the cardiac output, and vascular abnormalities in IPF include (a) heterogeneous vessel formation throughout fibrotic lung, including the development of abnormal dilated vessels and anastomoses; (b) abnormal spatially distributed populations of endothelial cells (ECs); (c) dysregulation of endothelial protective pathways such as prostacyclin signaling; and (d) an increased frequency of common vascular and metabolic comorbidities. Here, we propose that vascular and EC abnormalities are both causal and consequential in the pathobiology of IPF and that fuller evaluation of dysregulated pathways may lead to effective therapies and a cure for this devastating disease.
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15
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Zhu J, Zhou D, Wang J, Yang Y, Chen D, He F, Li Y. A Causal Atlas on Comorbidities in Idiopathic Pulmonary Fibrosis: A Bidirectional Mendelian Randomization Study. Chest 2023; 164:429-440. [PMID: 36870387 DOI: 10.1016/j.chest.2023.02.038] [Citation(s) in RCA: 26] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Revised: 02/21/2023] [Accepted: 02/24/2023] [Indexed: 03/06/2023] Open
Abstract
BACKGROUND Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease with a high burden of both pulmonary and extrapulmonary comorbidities. RESEARCH QUESTION Do these comorbidities have causal relationships with IPF? STUDY DESIGN AND METHODS We searched PubMed to pinpoint possible IPF-related comorbid conditions. Bidirectional Mendelian randomization (MR) was performed using summary statistics from the largest genome-wide association studies for these diseases to date in a two-sample setting. Findings were verified using multiple MR approaches under different model assumptions, replication datasets for IPF, and secondary phenotypes. RESULTS A total of 22 comorbidities with genetic data available were included. Bidirectional MR analyses showed convincing evidence for two comorbidities and suggestive evidence for four comorbidities. Gastroesophageal reflux disease, VTE, and hypothyroidism were associated causally with an increased risk of IPF, whereas COPD was associated causally with a decreased risk of IPF. For the reverse direction, IPF showed causal associations with a higher risk of lung cancer, but a reduced risk of hypertension. Follow-up analyses of pulmonary function parameters and BP measures supported the causal effect of COPD on IPF and the causal effect of IPF on hypertension. INTERPRETATION The present study suggested the causal associations between IPF and certain comorbidities from a genetic perspective. Further research is needed to understand the mechanisms of these associations.
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Affiliation(s)
- Jiahao Zhu
- Department of Epidemiology and Health Statistics, School of Public Health, Hangzhou Medical College, Hangzhou, China
| | - Dan Zhou
- School of Public Health and the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN
| | - Jing Wang
- Department of Epidemiology and Health Statistics, School of Public Health, Hangzhou Medical College, Hangzhou, China
| | - Ye Yang
- Department of Epidemiology and Health Statistics, School of Public Health, Hangzhou Medical College, Hangzhou, China
| | - Dingwan Chen
- Research Center on Primary Health of Zhejiang Province, School of Public Health, Hangzhou Medical College, Hangzhou, China
| | - Fan He
- Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China
| | - Yingjun Li
- Department of Epidemiology and Health Statistics, School of Public Health, Hangzhou Medical College, Hangzhou, China.
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16
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Morgan A, Gupta RS, George PM, Quint JK. Validation of the recording of idiopathic pulmonary fibrosis in routinely collected electronic healthcare records in England. BMC Pulm Med 2023; 23:256. [PMID: 37434192 DOI: 10.1186/s12890-023-02550-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Accepted: 07/05/2023] [Indexed: 07/13/2023] Open
Abstract
BACKGROUND Routinely-collected healthcare data provide a valuable resource for epidemiological research. Validation studies have shown that for most conditions, simple lists of clinical codes can reliably be used for case finding in primary care, however, studies exploring the robustness of this approach are lacking for diseases such as idiopathic pulmonary fibrosis (IPF) which are largely managed in secondary care. METHOD Using the UK's Clinical Practice Research Datalink (CPRD) Aurum dataset, which comprises patient-level primary care records linked to national hospital admissions and cause-of-death data, we compared the positive predictive value (PPV) of eight diagnostic algorithms. Algorithms were developed based on the literature and IPF diagnostic guidelines using combinations of clinical codes in primary and secondary care (SNOMED-CT or ICD-10) with/without additional information. The positive predictive value (PPV) was estimated for each algorithm using the death record as the gold standard. Utilization of the reviewed codes across the study period was observed to evaluate any change in coding practices over time. RESULT A total of 17,559 individuals had a least one record indicative of IPF in one or more of our three linked datasets between 2008 and 2018. The PPV of case-finding algorithms based on clinical codes alone ranged from 64.4% (95%CI:63.3-65.3) for a "broad" codeset to 74.9% (95%CI:72.8-76.9) for a "narrow" codeset comprising highly-specific codes. Adding confirmatory evidence, such as a CT scan, increased the PPV of our narrow code-based algorithm to 79.2% (95%CI:76.4-81.8) but reduced the sensitivity to under 10%. Adding evidence of hospitalisation to the standalone code-based algorithms also improved PPV, (PPV = 78.4 vs. 64.4%; sensitivity = 53.5% vs. 38.1%). IPF coding practices changed over time, with the increased use of specific IPF codes. CONCLUSION High diagnostic validity was achieved by using a restricted set of IPF codes. While adding confirmatory evidence increased diagnostic accuracy, the benefits of this approach need to be weighed against the inevitable loss of sample size and convenience. We would recommend use of an algorithm based on a broader IPF code set coupled with evidence of hospitalisation.
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Affiliation(s)
- Ann Morgan
- School of Public Health, Imperial College London, Level 9, Sir Michael Uren Hub, White City Campus, 86 Wood Lane, W12 0BZ, London, UK
- National Heart and Lung Institute, Imperial College London, Level 9, Sir Michael Uren Hub, White City Campus, 86 Wood Lane, W12 0BZ, London, UK
| | - Rikisha Shah Gupta
- School of Public Health, Imperial College London, Level 9, Sir Michael Uren Hub, White City Campus, 86 Wood Lane, W12 0BZ, London, UK
- National Heart and Lung Institute, Imperial College London, Level 9, Sir Michael Uren Hub, White City Campus, 86 Wood Lane, W12 0BZ, London, UK
| | - Peter M George
- National Heart and Lung Institute, Imperial College London, Level 9, Sir Michael Uren Hub, White City Campus, 86 Wood Lane, W12 0BZ, London, UK
- Interstitial Lung Disease Unit, Royal Brompton and Harefield NHS Foundation Trust, London, UK
- NIHR Imperial Biomedical Research Centre, The Bays, Entrance, 2 S Wharf Rd, W2 1NY, London, UK
| | - Jennifer K Quint
- School of Public Health, Imperial College London, Level 9, Sir Michael Uren Hub, White City Campus, 86 Wood Lane, W12 0BZ, London, UK.
- National Heart and Lung Institute, Imperial College London, Level 9, Sir Michael Uren Hub, White City Campus, 86 Wood Lane, W12 0BZ, London, UK.
- NIHR Imperial Biomedical Research Centre, The Bays, Entrance, 2 S Wharf Rd, W2 1NY, London, UK.
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17
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Yanagihara T, Guignabert C, Kolb MRJ. Endothelial cells in pulmonary fibrosis: more than a bystander. Eur Respir J 2023; 61:2300407. [PMID: 37290810 DOI: 10.1183/13993003.00407-2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Accepted: 03/11/2023] [Indexed: 06/10/2023]
Affiliation(s)
- Toyoshi Yanagihara
- Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Christophe Guignabert
- Université Paris-Saclay, Inserm, UMR_S 999, Hypertension pulmonaire: physiopathologie et innovation thérapeutique, Le Kremli-Bicêtre, France
| | - Martin R J Kolb
- Firestone Institute for Respiratory Health, Research Institute at St Joseph's Healthcare, Department of Medicine, McMaster University, Hamilton, ON, Canada
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18
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Sonaglioni A, Caminati A, Re M, Elia D, Trevisan R, Granato A, Zompatori M, Lombardo M, Harari S. Prognostic role of CHA 2DS 2-VASc score for mortality risk assessment in non-advanced idiopathic pulmonary fibrosis: a preliminary observation. Intern Emerg Med 2023; 18:755-767. [PMID: 36966265 PMCID: PMC10039767 DOI: 10.1007/s11739-023-03219-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Accepted: 02/05/2023] [Indexed: 03/27/2023]
Abstract
During the last decade, the CHA2DS2-VASc score has been used for stratifying the mortality risk in both atrial fibrillation (AF) and non-AF patients. However, no previous study considered this score as a prognostic indicator in non-AF patients with mild-to-moderate idiopathic pulmonary fibrosis (IPF). All consecutive non-AF patients with mild-to-moderate IPF, diagnosed between January 2016 and December 2018 at our Institution, entered this study. All patients underwent physical examination, blood tests, spirometry, high-resolution computed tomography and transthoracic echocardiography. CHA2DS2-VASc score, Gender-Age-Physiology (GAP) index and Charlson Comorbidity Index (CCI) were determined in all patients. Primary endpoint was all-cause mortality, while the secondary endpoint was the composite of all-cause mortality and rehospitalizations for all causes over mid-term follow-up. 103 consecutive IPF patients (70.7 ± 7.3 yrs, 79.6% males) were retrospectively analyzed. At the basal evaluation, CHA2DS2-VASc score, GAP index and CCI were 3.7 ± 1.6, 3.6 ± 1.2 and 5.5 ± 2.3, respectively. Mean follow-up was 3.5 ± 1.3 yrs. During the follow-up period, 29 patients died and 43 were re-hospitalized (44.2% due to cardiopulmonary causes). On multivariate Cox regression analysis, CHA2DS2-VASc score (HR 2.15, 95% CI 1.59-2.91) and left ventricular ejection fraction (LVEF) (HR 0.91, 95% CI 0.86-0.97) were independently associated with all-cause mortality in IPF patients. CHA2DS2-VASc score (HR 1.66, 95% CI 1.39-1.99) and LVEF (HR 0.94, 95% CI 0.90-0.98) also predicted the secondary endpoint in the same study group. CHA2DS2-VASc score > 4 was the optimal cut-off for predicting both outcomes. At mid-term follow-up, a CHA2DS2-VASc score > 4 predicts an increased risk of all-cause mortality and rehospitalizations for all causes in non-AF patients with mild-to-moderate IPF.
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Affiliation(s)
| | - Antonella Caminati
- Division of Pneumology, Semi-Intensive Care Unit, MultiMedica IRCCS, Milan, Italy.
| | - Margherita Re
- Division of Internal Medicine, MultiMedica IRCCS, Milan, Italy
| | - Davide Elia
- Division of Pneumology, Semi-Intensive Care Unit, MultiMedica IRCCS, Milan, Italy
| | | | - Alberto Granato
- Department of Veterinary Sciences, University of Turin, Turin, Italy
| | | | | | - Sergio Harari
- Division of Pneumology, Semi-Intensive Care Unit, MultiMedica IRCCS, Milan, Italy
- Division of Internal Medicine, MultiMedica IRCCS, Milan, Italy
- Department of Clinical Sciences and Community Health, Università Di Milano, Milan, Italy
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19
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Mohammadi-Nejad AR, Allen RJ, Kraven LM, Leavy OC, Jenkins RG, Wain LV, Auer DP, Sotiropoulos SN. Mapping brain endophenotypes associated with idiopathic pulmonary fibrosis genetic risk. EBioMedicine 2022; 86:104356. [PMID: 36413936 PMCID: PMC9677133 DOI: 10.1016/j.ebiom.2022.104356] [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] [Received: 04/01/2022] [Revised: 10/16/2022] [Accepted: 10/24/2022] [Indexed: 11/21/2022] Open
Abstract
BACKGROUND Idiopathic pulmonary fibrosis (IPF) is a serious disease of the lung parenchyma. It has a known polygenetic risk, with at least seventeen regions of the genome implicated to date. Growing evidence suggests linked multimorbidity of IPF with neurodegenerative or affective disorders. However, no study so far has explicitly explored links between IPF, associated genetic risk profiles, and specific brain features. METHODS We exploited imaging and genetic data from more than 32,000 participants available through the UK Biobank population-level resource to explore links between IPF genetic risk and imaging-derived brain endophenotypes. We performed a brain-wide imaging-genetics association study between the presence of 17 known IPF risk variants and 1248 multi-modal imaging-derived features, which characterise brain structure and function. FINDINGS We identified strong associations between cortical morphological features, white matter microstructure and IPF risk loci in chromosomes 17 (17q21.31) and 8 (DEPTOR). Through co-localisation analysis, we confirmed that cortical thickness in the anterior cingulate and more widespread white matter microstructure changes share a single causal variant with IPF at the chromosome 8 locus. Post-hoc preliminary analysis suggested that forced vital capacity may partially mediate the association between the DEPTOR variant and white matter microstructure, but not between the DEPTOR risk variant and cortical thickness. INTERPRETATION Our results reveal the associations between IPF genetic risk and differences in brain structure, for both cortex and white matter. Differences in tissue-specific imaging signatures suggest distinct underlying mechanisms with focal cortical thinning in regions with known high DEPTOR expression, unrelated to lung function, and more widespread microstructural white matter changes consistent with hypoxia or neuroinflammation with potential mediation by lung function. FUNDING This study was supported by the NIHR Nottingham Biomedical Research Centre and the UK Medical Research Council.
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Affiliation(s)
- Ali-Reza Mohammadi-Nejad
- National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Queens Medical Centre, Nottingham, United Kingdom; Sir Peter Mansfield Imaging Centre & Mental Health and Clinical Neurosciences, School of Medicine, University of Nottingham, Nottingham, United Kingdom
| | - Richard J Allen
- Department of Health Sciences, University of Leicester, Leicester, United Kingdom
| | - Luke M Kraven
- Department of Health Sciences, University of Leicester, Leicester, United Kingdom
| | - Olivia C Leavy
- Department of Health Sciences, University of Leicester, Leicester, United Kingdom
| | - R Gisli Jenkins
- National Heart and Lung Institute, Imperial College London, London, United Kingdom; Department of Interstitial Lung Disease, Royal Brompton and Harefield Hospital, Guys and St Thomas' NHS Foundation Trust, London, United Kingdom
| | - Louise V Wain
- Department of Health Sciences, University of Leicester, Leicester, United Kingdom; National Institute for Health Research (NIHR) Leicester Respiratory Biomedical Research Centre, Glenfield Hospital, Leicester, United Kingdom
| | - Dorothee P Auer
- National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Queens Medical Centre, Nottingham, United Kingdom; Sir Peter Mansfield Imaging Centre & Mental Health and Clinical Neurosciences, School of Medicine, University of Nottingham, Nottingham, United Kingdom.
| | - Stamatios N Sotiropoulos
- National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Queens Medical Centre, Nottingham, United Kingdom; Sir Peter Mansfield Imaging Centre & Mental Health and Clinical Neurosciences, School of Medicine, University of Nottingham, Nottingham, United Kingdom.
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20
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Stancil IT, Michalski JE, Schwartz DA. An Airway-Centric View of Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med 2022; 206:410-416. [PMID: 35446237 PMCID: PMC12039158 DOI: 10.1164/rccm.202109-2219pp] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Accepted: 04/20/2022] [Indexed: 11/16/2022] Open
Affiliation(s)
| | | | - David A Schwartz
- Department of Medicine and
- Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, Colorado
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21
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Lai J, Feng S, Xu S, Liu X. Effects of oral anticoagulant therapy in patients with pulmonary diseases. Front Cardiovasc Med 2022; 9:987652. [PMID: 36035947 PMCID: PMC9399807 DOI: 10.3389/fcvm.2022.987652] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Accepted: 07/26/2022] [Indexed: 11/13/2022] Open
Abstract
BackgroundTo evaluate the effect of oral anticoagulants (OACs) therapy, including vitamin K antagonist (VKA) and direct oral anticoagulants (DOAC) in patients with pulmonary diseases.MethodsLiterature from PubMed, MEDLINE, and Cochrane Library were screened until June 2022. Studies assessing OACs for pulmonary hypertension (PH), pulmonary embolism (PE), pulmonary fibrosis (PF), or chronic obstructive pulmonary disease (COPD) were evaluated for inclusion.ResultsOur study indicated that in patients with PH, PE, and COPD, OACs could significantly reduce the mortality risk, and the effects of VKA and DOACs without statistical difference in reducing the risk of recurrent embolism events. In patients with sclerosis-associated pulmonary arterial hypertension (SSc-PAH) or idiopathic pulmonary fibrosis (IPF), vitamin K antagonist (warfarin) significantly increased the mortality risk, while DOACs were not. As for the safety outcome of OACs, existing studies indicate that compared with patients treated with warfarin, the users of DOAC have a lower risk of major bleeding, while there is no statistical significance between them in non-major bleeding events. In current guidelines, the anticoagulation regimen for patients with pulmonary disease has not been defined. The results of our study confirm that DOACs (apixaban, rivaroxaban, dabigatran, and edoxaban) are superior to VKAs in the efficacy and safety outcomes of patients with pulmonary disease.ConclusionsOral anticoagulant therapy brings benefits to patients with PH, PE, or COPD, while the anticoagulation regimen for patients with SSc-PAH or IPF requires serious consideration. Compared with VKA, DOAC is a non-inferior option for anticoagulation in pulmonary disease treatment. Further studies are still needed to provide more reliable evidence about the safety outcome of pulmonary disease anticoagulation.
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Affiliation(s)
- Jiying Lai
- Department of Critical Care Medicine, The First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Shenghui Feng
- Queen Mary School, Medical Department, Nanchang University, Nanchang, China
| | - Shuo Xu
- Department of Respiratory and Critical Care Medicine, The Ganzhou People's Hospital, The Affiliated Ganzhou Hospital of Nanchang University, Ganzhou, China
- Shuo Xu
| | - Xin Liu
- Department of Critical Care Medicine, The First Affiliated Hospital of Gannan Medical University, Ganzhou, China
- *Correspondence: Xin Liu
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22
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Koteci A, Morgan AD, Portas L, Whittaker HR, Kallis C, George PM, Quint JK. Left-sided heart failure burden and mortality in idiopathic pulmonary fibrosis: a population-based study. BMC Pulm Med 2022; 22:190. [PMID: 35549901 PMCID: PMC9097426 DOI: 10.1186/s12890-022-01973-5] [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: 11/16/2021] [Accepted: 04/28/2022] [Indexed: 12/02/2022] Open
Abstract
Background Cardiovascular disease is prevalent in idiopathic pulmonary fibrosis (IPF), yet the extent of left-sided heart failure (HF) burden, whether this has changed with time and whether HF impacts mortality risk in these patients are unknown. The aims of this study were therefore to determine the temporal trends in incidence and prevalence of left-sided HF in patients with IPF in England and compare these to published estimates in the general population and those with comparable chronic respiratory conditions such as chronic obstructive pulmonary disease (COPD), as well as determine the risk of all-cause and cause-specific mortality in patients with comorbid left-sided HF and IPF at population-level using electronic healthcare data. Methods Clinical Practice Research Datalink (CPRD) Aurum primary-care data linked to mortality and secondary-care data was used to identify IPF patients in England. Left-sided HF prevalence and incidence rates were calculated for each calendar year between 2010 and 2019, stratified by age and sex. Risk of all-cause, cardiovascular and IPF-specific mortality was calculated using multivariate Cox regression. Results From 40,577patients with an IPF code in CPRD Aurum, 25, 341 IPF patients met inclusion criteria. Left-sided HF prevalence decreased from 33.4% (95% CI 32.2–34.6) in 2010 to 20.9% (20.0–21.7) in 2019. Left-sided HF incidence rate per 100 person-years (95% CI) remained stable between 2010 and 2017 but decreased from 4.3 (3.9–4.8) in 2017 to 3.4 (3.0–3.9) in 2019. Throughout follow-up, prevalence and incidence were higher in men and with increasing age. Comorbid HF was associated with poorer survival (adjusted HR (95%CI) 1.08 (1.03–1.14) for all-cause mortality; 1.32 (1.09–1.59) for cardiovascular mortality). Conclusion Left-sided HF burden in IPF patients in England remains high, with incidence almost 4 times higher than in COPD, a comparable lung disease with similar cardiovascular risk factors. Comorbid left-sided HF is also a poor prognostic marker. More substantial reduction in left-sided HF prevalence than incidence suggests persistently high IPF mortality. Given rising IPF incidence in the UK, this calls for better management of comorbidities such as left-sided HF to help optimise IPF survival. Supplementary Information The online version contains supplementary material available at 10.1186/s12890-022-01973-5.
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Affiliation(s)
- Ardita Koteci
- National Heart and Lung Institute, Imperial College London, Emmanuel Kaye Building, 1B Manresa Road, London, SW3 6LR, UK.,NIHR Imperial Biomedical Research Centre, London, UK
| | - Ann D Morgan
- National Heart and Lung Institute, Imperial College London, Emmanuel Kaye Building, 1B Manresa Road, London, SW3 6LR, UK.,NIHR Imperial Biomedical Research Centre, London, UK
| | - Laura Portas
- National Heart and Lung Institute, Imperial College London, Emmanuel Kaye Building, 1B Manresa Road, London, SW3 6LR, UK.,NIHR Imperial Biomedical Research Centre, London, UK
| | - Hannah R Whittaker
- National Heart and Lung Institute, Imperial College London, Emmanuel Kaye Building, 1B Manresa Road, London, SW3 6LR, UK.,NIHR Imperial Biomedical Research Centre, London, UK
| | - Constantinos Kallis
- National Heart and Lung Institute, Imperial College London, Emmanuel Kaye Building, 1B Manresa Road, London, SW3 6LR, UK.,NIHR Imperial Biomedical Research Centre, London, UK
| | - Peter M George
- National Heart and Lung Institute, Imperial College London, Emmanuel Kaye Building, 1B Manresa Road, London, SW3 6LR, UK.,Royal Brompton Hospital, London, UK
| | - Jennifer K Quint
- National Heart and Lung Institute, Imperial College London, Emmanuel Kaye Building, 1B Manresa Road, London, SW3 6LR, UK. .,NIHR Imperial Biomedical Research Centre, London, UK. .,Royal Brompton Hospital, London, UK.
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23
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Value of Cardiopulmonary Exercise Testing in Prognostic Assessment of Patients with Interstitial Lung Diseases. J Clin Med 2022; 11:jcm11061609. [PMID: 35329935 PMCID: PMC8954900 DOI: 10.3390/jcm11061609] [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] [Received: 01/04/2022] [Revised: 03/01/2022] [Accepted: 03/11/2022] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND Interstitial lung disease (ILD) is associated with high rates of comorbidities and non-infectious lung disease mortality. Against this background, we aimed to evaluate the prognostic capacity of lung function and cardiopulmonary exercise testing (CPET) in patients with ILD. MATERIALS AND METHODS A total of 183 patients with diverse ILD entities were included in this monocentric analysis. Prediction models were determined using Cox regression models with age, sex, body mass index (BMI), and all parameters from pulmonary function testing and CPET. Kaplan-Meier curves were plotted for selected variables. RESULTS The median follow-up period was 3.0 ± 2.5 years. Arterial hypertension (57%) and pulmonary hypertension (38%) were the leading comorbidities. The Charlson comorbidity index score was 2 ± 2 points. The 3-year and 5-year survival rates were 68% and 50%, respectively. VO2peak (mL/kg/min or %pred.) was identified as a significant prognostic parameter in patients with ILD. The cut-off value for discriminating mortality was 61%. CONCLUSION The present analyses consistently revealed the high prognostic power of VO2peak %pred. and other parameters evaluating breathing efficacy (VÉ/VCO2 @AT und VÉ/VCO2 slope) in ILD patients. VO2peak %pred., in contrast to the established prognostic values FVC %pred., DLCO/KCO %pred., and GAP, showed an even higher prognostic ability in all statistical models.
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24
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Cardiovascular Morbidity in Individuals with Impaired FEV1. Curr Cardiol Rep 2022; 24:163-182. [PMID: 35038132 DOI: 10.1007/s11886-022-01636-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/04/2021] [Indexed: 11/03/2022]
Abstract
PURPOSE OF REVIEW This review is intended to give an overview of the epidemiology of cardiovascular morbidity and mortality in patients with impaired lung function with an emphasis on patients with COPD. RECENT FINDINGS Despite shared risk factors, lung disease is an emerging independent risk factor for cardiovascular disease and cardio-vascular disease (CVD) outcomes. Both CVD and chronic lung disease contribute significantly to overall mortality. Especially patients with chronic obstructive pulmonary disease (COPD) are at high risk for CVD-related mortality. In patients with chronic lung disease, a low index of suspicion should be maintained to assess for CVD and vice versa. Early detection of chronic lung disease as a potentially modifiable CVD risk factor could have important impact on patient outcomes.
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25
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Charokopos A, Moua T, Ryu JH, Smischney NJ. Acute exacerbation of interstitial lung disease in the intensive care unit. World J Crit Care Med 2022; 11:22-32. [PMID: 35433309 PMCID: PMC8788209 DOI: 10.5492/wjccm.v11.i1.22] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Revised: 08/04/2021] [Accepted: 11/15/2021] [Indexed: 02/06/2023] Open
Abstract
Acute exacerbations of interstitial lung disease (AE-ILD) represent an acute, frequent and often highly morbid event in the disease course of ILD patients. Admission in the intensive care unit (ICU) is very common and the need for mechanical ventilation arises early. While non-invasive ventilation has shown promise in staving off intubation in selected patients, it is unclear whether mechanical ventilation can alter the exacerbation course unless it is a bridge to lung transplantation. Risk stratification using clinical and radiographic findings, and early palliative care involvement, are important in ICU care. In this review, we discuss many of the pathophysiological aspects of AE-ILD and raise the hypothesis that ventilation strategies used in acute respiratory distress syndrome might be implemented in AE-ILD. We present possible decision-making and management algorithms that can be used by the intensivist when caring for these patients.
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Affiliation(s)
- Antonios Charokopos
- Department of Medicine, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN 55905, United States
| | - Teng Moua
- Department of Medicine, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN 55905, United States
| | - Jay H Ryu
- Department of Medicine, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN 55905, United States
| | - Nathan J Smischney
- Department of Anesthesiology and Perioperative Medicine, Division of Critical Care Medicine, Mayo Clinic, Rochester, MN 55905, United States
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26
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Sobiecka M, Szturmowicz M, Lewandowska K, Kowalik A, Łyżwa E, Zimna K, Barańska I, Jakubowska L, Kuś J, Langfort R, Tomkowski W. Chronic hypersensitivity pneumonitis is associated with an increased risk of venous thromboembolism: a retrospective cohort study. BMC Pulm Med 2021; 21:416. [PMID: 34920701 PMCID: PMC8684138 DOI: 10.1186/s12890-021-01794-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Accepted: 12/14/2021] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Idiopathic pulmonary fibrosis (IPF) and chronic hypersensitivity pneumonitis share commonalities in pathogenesis shifting haemostasis balance towards the procoagulant and antifibrinolytic activity. Several studies have suggested an increased risk of venous thromboembolism in IPF. The association between venous thromboembolism and chronic hypersensitivity pneumonitis has not been studied yet.
Methods
A retrospective cohort study of IPF and chronic hypersensitivity pneumonitis patients diagnosed in single tertiary referral center between 2005 and 2018 was conducted. The incidence of symptomatic venous thromboembolism was evaluated. Risk factors for venous thromboembolism and survival among those with and without venous thromboembolism were assessed.
Results
A total of 411 (259 IPF and 152 chronic hypersensitivity) patients were included (mean age 66.7 ± 8.4 vs 51.0 ± 13.3 years, respectively). There were 12 (4.6%) incident cases of venous thromboembolism in IPF and 5 (3.3%) in chronic hypersensitivity pneumonitis cohort. The relative risk (RR) of venous thromboembolism in chronic hypersensitivity pneumonitis was not significantly different to that found in patients with IPF (7.1 vs 11.8/1000 person-years, RR 1.661 95% CI 0.545–6.019, respectively).
The treatment with systemic steroids (OR 5.38; 95% CI 1.65–18.8, p = 0.006) and GAP stage 3 (OR 7.85; 95% CI 1.49–34.9; p = 0.037) were significant risk factors for venous thromboembolism in IPF. Arterial hypertension and pulmonary hypertension significantly increased risk of venous thromboembolism in chronic hypersensitivity pneumonitis. There were no significant differences in survival between patients with and without venous thromboembolism.
Conclusions
The patients with chronic hypersensitivity pneumonitis have a marked increase in the risk of venous thromboembolism, similar to the patients with IPF. Venous thromboembolism does not affect the survival of patients with IPF and chronic hypersensitivity pneumonitis.
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27
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Warfarin Use Is Associated with Increased Mortality at One Year in Patients with Idiopathic Pulmonary Fibrosis. Pulm Med 2021; 2021:3432362. [PMID: 34868680 PMCID: PMC8639231 DOI: 10.1155/2021/3432362] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2021] [Revised: 11/09/2021] [Accepted: 11/09/2021] [Indexed: 11/21/2022] Open
Abstract
Objectives We studied the safety and efficacy of warfarin compared to direct acting oral anticoagulant use in patients with IPF. Methods We conducted a retrospective cohort study of all patients with IPF who were prescribed warfarin or direct acting oral anticoagulants (DOACs) for cardiac or thromboembolic indications and followed at our institute for their care. Univariate tests and multivariable logistic regression analyses were used for assessing association of variables with outcomes. Results A total of 73 patients were included in the study with 28 and 45 patients in the warfarin and DOAC groups, respectively. Univariable analysis revealed a significant difference in mortality in one year between warfarin and DOAC groups (7/28 vs. 3/45, p value 0.027). Significantly more patients in the warfarin group suffered an exacerbation that required hospitalization within one year (9/28 vs. 5/45, p value 0.026). Multivariate logistic regression analysis showed that anticoagulation with warfarin was independently associated with mortality at one-year follow-up (OR: 77.4, 95% CI: 5.94–409.3, p value: 0.007). Conclusion In our study of patients with IPF requiring anticoagulants, we noted statistically significant higher mortality with warfarin anticoagulation when compared to DOAC use. Further larger prospective studies are needed to confirm these findings.
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28
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Zhang WT, Wang XJ, Xue CM, Ji XY, Pan L, Weng WL, Li QY, Hua GD, Zhu BC. The Effect of Cardiovascular Medications on Disease-Related Outcomes in Idiopathic Pulmonary Fibrosis: A Systematic Review and Meta-Analysis. Front Pharmacol 2021; 12:771804. [PMID: 34858190 PMCID: PMC8632524 DOI: 10.3389/fphar.2021.771804] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Accepted: 10/11/2021] [Indexed: 12/20/2022] Open
Abstract
Background: Multiple studies have revealed that idiopathic pulmonary fibrosis (IPF) patients are more at risk for cardiovascular diseases and that many IPF patients receive cardiovascular medications like statins, angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), and anticoagulants. Existing studies have reported divergent findings on the link between cardiovascular medications and fibrotic disease processes. The aim of this study is to synthesize the evidence on the efficacy of cardiovascular medications in IPF. Methods: We searched studies reporting the effect of cardiovascular medications on IPF in the PubMed, Embase, Web of Science, Cochrane Library, and two Chinese databases (China National Knowledge Infrastructure database and China Wanfang database). We calculated survival data, forced vital capacity (FVC) decline, and IPF-related mortality to assess the efficacy of cardiovascular medications in IPF. We also estimated statistical heterogeneity by using I2 and Cochran Q tests, and publication bias was evaluated by risk of bias tools ROBINS-I. Results: A total of 12 studies were included in the analysis. The included studies had moderate-to-serious risk of bias. Statin use was associated with a reduction in mortality (hazard ratio (HR), 0.89; 95% CI 0.83-0.97). Meta-analysis did not demonstrate any significant relationship between statin use and the FVC decline (HR, 0.86; 95% CI 0.73-1.02), ACEI/ARB use, and survival data (HR, 0.92; 95% CI 0.73-1.15) as well as anticoagulant use and survival data (HR, 1.16; 95% CI 0.62-2.19). Conclusion: Our study suggested that there is a consistent relationship between statin therapy and survival data in IPF population. However, there is currently insufficient evidence to conclude the effect of ACEI, ARB, and anticoagulant therapy on IPF population especially to the disease-related outcomes in IPF.
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Affiliation(s)
- Wan-Tong Zhang
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Xu-Jie Wang
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Chun-Miao Xue
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Xin-Yu Ji
- Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China
| | - Lin Pan
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Wei-Liang Weng
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.,National Clinical Research Center for Chinese Medicine Cardiology, Beijing, China
| | - Qiu-Yan Li
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.,National Clinical Research Center for Chinese Medicine Cardiology, Beijing, China
| | - Guo-Dong Hua
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Bao-Chen Zhu
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
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Wang H, Yang R, Jin J, Wang Z, Li W. Impact of concomitant idiopathic pulmonary fibrosis on prognosis in lung cancer patients: A meta-analysis. PLoS One 2021; 16:e0259784. [PMID: 34767608 PMCID: PMC8589161 DOI: 10.1371/journal.pone.0259784] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Accepted: 10/26/2021] [Indexed: 02/05/2023] Open
Abstract
Background Current studies showed that idiopathic pulmonary fibrosis (IPF) may lead to a poor prognosis of lung cancer. We conducted a meta-analysis to explore the impact of concomitant IPF in lung cancer and its prognostic value. Methods We searched the databases of PubMed, Web of Science, Embase up to Feb 10th, 2021 for relevant researches and merged the hazard ratios (HRs) and 95% confidence intervals (CIs) to evaluate the association between concomitant IPF and overall survival (OS) in patients with lung cancer. Results Twelve studies involving 58424 patients were included in our meta-analysis. The results indicated that concomitant IPF was correlated with poor prognosis of lung cancer patients (HR = 1.99, 95%CI, 1.59–2.51). The association remained consistent after subgroup analysis and meta-regression stratified by study region, sample size, tumor histology, and therapy. In addition, our results were robust even after sensitivity analysis. Conclusions Concomitant IPF may be a prognostic factor of lung cancer, which can lead to poor survival. However, further studies were necessary for evidence in clinical application.
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Affiliation(s)
- Haoyu Wang
- Department of Respiratory and Critical Care Medicine, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, China
| | - Ruiyuan Yang
- Department of Respiratory and Critical Care Medicine, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, China
| | - Jing Jin
- Department of Respiratory and Critical Care Medicine, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, China
| | - Zhoufeng Wang
- Department of Respiratory and Critical Care Medicine, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, China
| | - Weimin Li
- Department of Respiratory and Critical Care Medicine, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, China
- * E-mail:
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Sonaglioni A, Caminati A, Lipsi R, Lombardo M, Harari S. Association between C-reactive protein and carotid plaque in mild-to-moderate idiopathic pulmonary fibrosis. Intern Emerg Med 2021; 16:1529-1539. [PMID: 33411265 DOI: 10.1007/s11739-020-02607-6] [Citation(s) in RCA: 4] [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: 10/13/2020] [Accepted: 12/14/2020] [Indexed: 01/03/2023]
Abstract
An association between C-reactive protein (CRP) levels and carotid plaque has never been investigated in idiopathic pulmonary fibrosis (IPF). The aim of this study was to evaluate the extent of carotid atherosclerosis in mild-to-moderate IPF and to assess its relationship to serum CRP. This observational retrospective case-control study included 60 consecutive IPF patients (73.8 ± 6.6 years, 45 males) and 60 matched controls, examined between Sep 2017 and Jan 2019. All patients underwent CRP assessment and a carotid Doppler ultrasonography. CRP levels were significantly higher in IPF patients than controls (0.2 ± 0.09 mg/dl vs 0.09 ± 0.04 mg/dl, p < 0.0001). A total of 46 plaques were detected, with higher prevalence in IPF patients than controls (38 vs 8, p < 0.0001). On univariate logistic regression the main variables independently associated with carotid plaque were: age (HR 1.09, 95% CI 1.03-1.16, p = 0.006), hypertension duration (HR 1.05, 95% CI 1.01-1.09, p = 0.01), diabetes duration (HR 1.09, 95% CI 1.01-1.18, p = 0.03), LDL-cholesterol (HR 1.07, 95% CI 1.04-1.10, p < 0.0001) and finally CRP levels (HR 1.73, 95% CI 0.59-5.00, p < 0.0001). Multivariate logistic regression analysis revealed that LDL-cholesterol (HR 1.05, 95% CI 1.01-1.08, p = 0.009) and CRP levels (HR 1.43, 95% CI 0.39-5.19, p < 0.0001) retained statistical significance. Common carotid artery-intima media thickness was significantly correlated with CRP levels in IPF patients (r = 0.86). SerumCRP might represent both an early marker and a potential therapeutic target for carotid atherosclerosis in mild-to-moderate IPF.
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Affiliation(s)
- Andrea Sonaglioni
- UO Di Cardiologia, Ospedale San Giuseppe MultiMedica IRCCS, Via San Vittore 12, 20123, Milan, Italy
| | - Antonella Caminati
- UO Di Pneumologia E Terapia Semi-Intensiva Respiratoria-Servizio Di Fisiopatologia Respiratoria Ed Emodinamica Polmonare, Ospedale San Giuseppe MultiMedica IRCCS, Via San Vittore 12, 20123, Milan, Italy.
| | - Roberto Lipsi
- UO Di Pneumologia E Terapia Semi-Intensiva Respiratoria-Servizio Di Fisiopatologia Respiratoria Ed Emodinamica Polmonare, Ospedale San Giuseppe MultiMedica IRCCS, Via San Vittore 12, 20123, Milan, Italy
| | - Michele Lombardo
- UO Di Cardiologia, Ospedale San Giuseppe MultiMedica IRCCS, Via San Vittore 12, 20123, Milan, Italy
| | - Sergio Harari
- UO Di Pneumologia E Terapia Semi-Intensiva Respiratoria-Servizio Di Fisiopatologia Respiratoria Ed Emodinamica Polmonare, Ospedale San Giuseppe MultiMedica IRCCS, Via San Vittore 12, 20123, Milan, Italy
- Dipartimento Di Scienze Mediche, Ospedale San Giuseppe MultiMedica IRCCS, Via San Vittore 12, 20123, Milan, Italy
- Dipartimento Di Scienze Cliniche E Di Comunità, Università Di Milano, Milan, Italy
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Kolonics-Farkas AM, Šterclová M, Mogulkoc N, Kus J, Hájková M, Müller V, Jovanovic D, Tekavec-Trkanjec J, Littnerová S, Hejduk K, Vašáková M. Anticoagulant Use and Bleeding Risk in Central European Patients with Idiopathic Pulmonary Fibrosis (IPF) Treated with Antifibrotic Therapy: Real-World Data from EMPIRE. Drug Saf 2021; 43:971-980. [PMID: 32734423 PMCID: PMC7497686 DOI: 10.1007/s40264-020-00978-5] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
INTRODUCTION Nintedanib, a tyrosine kinase receptor inhibitor, may be associated with increased bleeding risk. Thus, patients with an inherited predisposition to bleeding, or those receiving therapeutic doses of anticoagulants or high-dose antiplatelet therapy, have been excluded from clinical trials of nintedanib in idiopathic pulmonary fibrosis (IPF). OBJECTIVE Our objective was to examine real-world bleeding events in patients with IPF treated with antifibrotics, including those receiving anticoagulants and/or antiplatelet therapy. METHODS The European MultiPartner IPF Registry (EMPIRE) enrolled 2794 patients with IPF: group A (1828: no anticoagulant or antiplatelet treatment), group B (227: anticoagulant treatment), group C (659: antiplatelet treatment), and group D (80: anticoagulant and antiplatelet treatment). Overall, 673 (24.1%) received nintedanib and 933 (33.4%) received pirfenidone. Bleeding events and their relationship to antifibrotic and anticoagulation treatment were characterized. RESULTS Group A patients, versus those in groups B, C, and D, were typically younger and generally had the lowest comorbidity rates. A higher proportion of patients in groups A and C, versus group B, received nintedanib. Pirfenidone, most common in group D, was more evenly balanced across groups. In patients with reported bleeding events, seven of eight received nintedanib (groups A, C, and D). Bleeding incidence was 3.0, 0, 1.3, and 18.1 per 10,000 patient-years (groups A, B, C, and D, respectively). CONCLUSION Real-world data from EMPIRE showed that patients on anticoagulant medications received nintedanib less frequently, perhaps based on its mechanism of action. Overall, bleeding incidence was low (0.29%: nintedanib 0.25%; pirfenidone 0.04%) and irrespective of anticoagulant or antiplatelet therapy received (P = 0.072).
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Affiliation(s)
| | - Martina Šterclová
- Department of Respiratory Diseases of the First Faculty of Medicine, Charles University, Thomayer Hospital, Prague, Czech Republic
| | - Nesrin Mogulkoc
- Department of Pulmonary Medicine, Ege University Medical School, Izmir, Turkey
| | - Jan Kus
- Department of Pulmonary Diseases, Institute of Tuberculosis and Lung Diseases, Warsaw, Poland
| | - Marta Hájková
- Clinic of Pneumology and Phthisiology, University Hospital Bratislava, Bratislava, Slovakia
| | - Veronika Müller
- Department of Pulmonology, Semmelweis University, Tömő utca 25-29, Budapest, 1083, Hungary
| | - Dragana Jovanovic
- University Hospital of Pulmonology, Clinical Center of Serbia, Belgrade, Serbia
| | | | - Simona Littnerová
- Institute of Biostatistics and Analyses, Masaryk University, Faculty of Medicine, Brno, Czech Republic
| | - Karel Hejduk
- Institute of Biostatistics and Analyses, Masaryk University, Faculty of Medicine, Brno, Czech Republic
| | - Martina Vašáková
- Department of Respiratory Diseases of the First Faculty of Medicine, Charles University, Thomayer Hospital, Prague, Czech Republic
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López-Muñiz Ballesteros B, López-Herranz M, Lopez-de-Andrés A, Hernandez-Barrera V, Jiménez-García R, Carabantes-Alarcon D, Jiménez-Trujillo I, de Miguel-Diez J. Sex Differences in the Incidence and Outcomes of Patients Hospitalized by Idiopathic Pulmonary Fibrosis (IPF) in Spain from 2016 to 2019. J Clin Med 2021; 10:jcm10163474. [PMID: 34441772 PMCID: PMC8396834 DOI: 10.3390/jcm10163474] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Revised: 07/24/2021] [Accepted: 08/04/2021] [Indexed: 02/06/2023] Open
Abstract
(1) Background: To assess sex differences in the incidence, characteristics, procedures and outcomes of patients admitted with idiopathic pulmonary fibrosis (IPF); and to analyze variables associated with in-hospital mortality (IHM). (2) Methods: We analyzed data collected by the Spanish National Hospital Discharge Database, 2016-2019. (3) Results: We identified 13,278 hospital discharges (66.4% men) of IPF (primary diagnosis 32.33%; secondary diagnosis: 67.67%). Regardless of the diagnosis position, IPF incidence was higher among men than women, increasing with age. Men had 2.74 times higher IPF incidence than women. Comorbidity was higher for men in either primary or secondary diagnosis. After matching, men had higher prevalence of pulmonary embolism and pneumonia, and women of congestive heart failure, dementia, rheumatoid disease and pulmonary hypertension. Invasive ventilation, bronchoscopy and lung transplantation were received more often by men than women. IHM was higher among men with IPF as primary diagnosis than among women and increased with age in both sexes and among those who suffered cancer, pneumonia or required mechanical ventilation. (4) Conclusions: Incidence of IPF was higher among men than women, as well as comorbidity and use of bronchoscopy, ventilation and lung transplantation. IHM was worse among men than women with IPF as primary diagnosis, increasing with age, cancer, pneumonia or mechanical ventilation use.
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Affiliation(s)
| | - Marta López-Herranz
- Nursing Department, Faculty of Nursing, Physiotherapy and Podology, Universidad Complutense de Madrid, 28040 Madrid, Spain
- Correspondence: ; Tel.: +34-91-394-1521
| | - Ana Lopez-de-Andrés
- Department of Public Health & Maternal and Child Health, Faculty of Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain; (A.L.-d.-A.); (R.J.-G.); (D.C.-A.)
| | - Valentín Hernandez-Barrera
- Preventive Medicine and Public Health Teaching and Research Unit, Health Sciences Faculty, Universidad Rey Juan Carlos, Alcorcón, 28922 Madrid, Spain; (V.H.-B.); (I.J.-T.)
| | - Rodrigo Jiménez-García
- Department of Public Health & Maternal and Child Health, Faculty of Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain; (A.L.-d.-A.); (R.J.-G.); (D.C.-A.)
| | - David Carabantes-Alarcon
- Department of Public Health & Maternal and Child Health, Faculty of Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain; (A.L.-d.-A.); (R.J.-G.); (D.C.-A.)
| | - Isabel Jiménez-Trujillo
- Preventive Medicine and Public Health Teaching and Research Unit, Health Sciences Faculty, Universidad Rey Juan Carlos, Alcorcón, 28922 Madrid, Spain; (V.H.-B.); (I.J.-T.)
| | - Javier de Miguel-Diez
- Respiratory Department, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), 28007 Madrid, Spain;
- Department of Medicine, Faculty of Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain
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Kapnadak SG, Raghu G. Lung transplantation for interstitial lung disease. Eur Respir Rev 2021; 30:30/161/210017. [PMID: 34348979 DOI: 10.1183/16000617.0017-2021] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Accepted: 04/02/2021] [Indexed: 01/18/2023] Open
Abstract
Lung transplantation (LTx) can be a life-extending treatment option for patients with advanced and/or progressive fibrotic interstitial lung disease (ILD), especially idiopathic pulmonary fibrosis (IPF), fibrotic hypersensitivity pneumonitis, sarcoidosis and connective tissue disease-associated ILD. IPF is now the most common indication for LTx worldwide. Several unique features in patients with ILD can impact optimal timing of referral or listing for LTx, pre- or post-transplant risks, candidacy and post-transplant management. As the epidemiology of LTx and community practices have evolved, recent literature describes outcomes and approaches in higher-risk candidates. In this review, we discuss the unique and important clinical findings, course, monitoring and management of patients with IPF and other progressive fibrotic ILDs during pre-LTx evaluation and up to the day of transplantation; the need for co-management with clinical experts in ILD and LTx is emphasised. Some post-LTx complications are unique in these patient cohorts, which require prompt detection and appropriate management by experts in multiple disciplines familiar with telomere biology disorders and infectious, haematological, oncological and cardiac complications to enhance the likelihood of improved outcomes and survival of LTx recipients with IPF and other ILDs.
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Affiliation(s)
- Siddhartha G Kapnadak
- Division of Pulmonary, Critical Care and Sleep Medicine, Dept of Medicine, University of Washington, Seattle, WA, USA
| | - Ganesh Raghu
- Division of Pulmonary, Critical Care and Sleep Medicine, Dept of Medicine, University of Washington, Seattle, WA, USA .,Dept of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA
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Risk of recurrent venous thromboembolism and bleeding in patients with interstitial lung disease: a cohort study. J Thromb Thrombolysis 2021; 53:67-73. [PMID: 34232453 DOI: 10.1007/s11239-021-02518-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/24/2021] [Indexed: 10/20/2022]
Abstract
Interstitial lung disease (ILD) encompasses various parenchymal lung disorders, which has the potential to increase the risk of venous thromboembolism (VTE). To evaluate, in patients with ILD and VTE, the risk of recurrent VTE during follow-up after stopping anticoagulation. This was a cohort of patients with a first VTE recruited between 1997 and 2015. The primary outcome was adjudicated fatal or nonfatal recurrent VTE after stopping anticoagulation. Main secondary outcomes were major or clinically relevant non-major bleeding under anticoagulation. Among 4314 patients with VTE, 50 had ILD diagnosed before VTE. Of these, anticoagulation was stopped in 30 patients after a median duration of 180 days and continued indefinitely in 20 patients. During a median follow-up of 27.8 months after anticoagulation discontinuation, recurrent VTE occurred in 15 on 30 patients (annual incidence of 19.2 events per 100-person-years [95%CI 12.0-29.3], case-fatality rate of 6.7% [95%CI 1.21-29.8]). The risk of recurrence was threefold higher when VTE was unprovoked and case-fatality rate of recurrence was increased by 3 when VTE index was PE. During the anticoagulant period, (median duration of 8.6 months), 6 patients had a major or clinically relevant bleeding (annual incidence of 7.3 events per 100-person-years [95%CI 3.4-15.1], case-fatality rate of 16.7% [95%CI 3.0-56.4]). In patients with ILD, the risk of recurrent VTE after stopping anticoagulation and the risk of bleeding under anticoagulation were very high. Our results suggest that anticoagulation should not be prolonged beyond 3-6 months of anticoagulation in most of cases.
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Fukui M, Takamochi K, Suzuki K, Ando K, Matsunaga T, Hattori A, Oh S, Suzuki K. Outcomes of lung cancer surgery for patients with interstitial pneumonia and coronary disease. Surg Today 2021; 52:137-143. [PMID: 34136963 DOI: 10.1007/s00595-021-02319-0] [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: 01/14/2021] [Accepted: 04/22/2021] [Indexed: 10/21/2022]
Abstract
PURPOSE To evaluate the surgical outcomes of lung cancer patients with idiopathic interstitial pneumonia (IIP) and/or coronary artery disease (CAD). METHODS The subjects of this retrospective study were 2830 patients who underwent surgical resection for lung cancer between 2009 and 2018. Seventy-one patients (2.6%) had both IIP and CAD (FC group). The remaining patients were divided into those with IIP only (group F), those with CAD only (group C), and those without IIP or CAD (group N). We compared mortality and overall survival (OS) among the groups. RESULTS The 90-day mortality and OS were poorer in group FC than in groups C and N, but equivalent to those in group F. Multivariate analyses revealed that IIP (odds ratio [OR] 3.163; p = 0.001) and emphysema (2.588; p = 0.009) were predictors of 90-day mortality. IIP (OR 2.991, p < 0.001), diabetes (OR 1.241, p = 0.043), and a history of other cancers (OR 1.347, p = 0.011) were all predictors of OS. CONCLUSIONS Short-term and long-term mortality after lung cancer surgery were not dependent on coexistent CAD but were related to IIP. Thus, computed tomography (CT) should be done preoperatively to check for IIP, which is a risk factor for surgical mortality.
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Affiliation(s)
- Mariko Fukui
- Departments of General Thoracic Surgery, Juntendo University School of Medicine, 1-3, Hongo 3-chome, Bunkyo-ku, Tokyo, 113-8431, Japan.
| | - Kazuya Takamochi
- Departments of General Thoracic Surgery, Juntendo University School of Medicine, 1-3, Hongo 3-chome, Bunkyo-ku, Tokyo, 113-8431, Japan
| | - Kazuhiro Suzuki
- Departments of Radiology, Juntendo University School of Medicine, Tokyo, Japan
| | - Katsutoshi Ando
- Departments of Respiratory Medicine, Juntendo University School of Medicine, Tokyo, Japan
| | - Takeshi Matsunaga
- Departments of General Thoracic Surgery, Juntendo University School of Medicine, 1-3, Hongo 3-chome, Bunkyo-ku, Tokyo, 113-8431, Japan
| | - Aritoshi Hattori
- Departments of General Thoracic Surgery, Juntendo University School of Medicine, 1-3, Hongo 3-chome, Bunkyo-ku, Tokyo, 113-8431, Japan
| | - Shiaki Oh
- Departments of General Thoracic Surgery, Juntendo University School of Medicine, 1-3, Hongo 3-chome, Bunkyo-ku, Tokyo, 113-8431, Japan
| | - Kenji Suzuki
- Departments of General Thoracic Surgery, Juntendo University School of Medicine, 1-3, Hongo 3-chome, Bunkyo-ku, Tokyo, 113-8431, Japan
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The effect of statin therapy on disease-related outcomes in idiopathic pulmonary fibrosis: A systematic review and meta-analysis. Respir Med Res 2021; 80:100792. [PMID: 34091200 DOI: 10.1016/j.resmer.2020.100792] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Revised: 09/15/2020] [Accepted: 09/24/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND Idiopathic pulmonary fibrosis is a progressive disease and antifibrotic therapies do not reverse existing fibrosis. There has been emerging evidence of potential role for statins in idiopathic pulmonary fibrosis. The aim of this review is to synthesise the evidence on the efficacy of statins in idiopathic pulmonary fibrosis, focusing on associations with all-cause mortality, disease-specific mortality and change in pulmonary function. METHODS Medline and Embase were reviewed to identify relevant publications. Studies were selected if they examined disease-related outcomes including mortality, pulmonary function and adverse events in people with idiopathic pulmonary fibrosis receiving statin therapy. RESULTS Five studies with a total of 3407 people with IPF were selected and analysed. The overall risk of bias of five included studies was moderate to serious. In the fixed effect meta-analysis, statin use was associated with a reduction in mortality (RR 0.8; 95% CI 0.72-0.99). However, in the random effects model, there was no longer any significant association between statin use and all-cause mortality (RR 0.87; 95% CI 0.68-1.12). There was no statistically significant association between statin use and decline in FVC % predicted. CONCLUSION There is currently insufficient evidence to conclude the effect of statin therapy on disease-related outcomes in idiopathic pulmonary fibrosis. Considering the limitations of available literature, we would recommend a prospective cohort study with capture of dosage and preparation of statin, statin adherence and use of concurrent antifibrotic treatment. PROSPERO REGISTRATION NUMBER CRD42019122745.
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Alfaro TM, Robalo Cordeiro C. Comorbidity in idiopathic pulmonary fibrosis - what can biomarkers tell us? Ther Adv Respir Dis 2021; 14:1753466620910092. [PMID: 32167024 PMCID: PMC7074506 DOI: 10.1177/1753466620910092] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Idiopathic pulmonary fibrosis (IPF) is characterized by progressive parenchymal scarring, leading to dyspnoea, respiratory failure and premature death. Although IPF is confined to the lungs, the importance of IPF comorbidities such as pulmonary hypertension and ischaemic heart disease, lung cancer, emphysema/chronic obstructive pulmonary disease, gastroesophageal reflux, sleep apnoea and depression has been increasingly recognized. These comorbidities may be associated with increased mortality and significant loss of quality of life, so their identification and management are vital. The development of good-quality biomarkers could lead to numerous gains in the management of these patients. Biomarkers can be used for the identification of predisposed individuals, early diagnosis, assessment of prognosis, selection of best treatment and assessment of response to treatment. However, the role of biomarkers for IPF comorbidities is still quite limited, and mostly based on evidence coming from populations without IPF. The future development of new biomarker studies could be informed by those that have been studied independently for each of these conditions. For now, clinicians should be mostly attentive to clinical manifestations of IPF comorbidities, and use validated diagnostic methods for diagnosis. As research on biomarkers of most common diseases continues, it is expected that useful biomarkers are developed for these diseases and then validated for IPF populations. The reviews of this paper are available via the supplemental material section.
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Affiliation(s)
- Tiago M Alfaro
- Pneumology Unit, Centro Hospital e Universitário de Coimbra, Coimbra, Portugal.,Centre of Pneumology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal
| | - Carlos Robalo Cordeiro
- Pneumology Unit, Centro Hospital e Universitário de Coimbra, Praceta Mota Pinto, Coimbra 3000-085, Portugal.,Centre of Pneumology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal
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Venous Thromboembolic Disease in Chronic Inflammatory Lung Diseases: Knowns and Unknowns. J Clin Med 2021; 10:jcm10102061. [PMID: 34064992 PMCID: PMC8151562 DOI: 10.3390/jcm10102061] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2021] [Revised: 05/05/2021] [Accepted: 05/07/2021] [Indexed: 12/13/2022] Open
Abstract
Persistent inflammation within the respiratory tract underlies the pathogenesis of numerous chronic pulmonary diseases. There is evidence supporting that chronic lung diseases are associated with a higher risk of venous thromboembolism (VTE). However, the relationship between lung diseases and/or lung function with VTE is unclear. Understanding the role of chronic lung inflammation as a predisposing factor for VTE may help determine the optimal management and aid in the development of future preventative strategies. We aimed to provide an overview of the relationship between the most common chronic inflammatory lung diseases and VTE. Asthma, chronic obstructive pulmonary disease, interstitial lung diseases, or tuberculosis increase the VTE risk, especially pulmonary embolism (PE), compared to the general population. However, high suspicion is needed to diagnose a thrombotic event early as the clinical presentation inevitably overlaps with respiratory disorders. PE risk increases with disease severity and exacerbations. Hence, hospitalized patients should be considered for thromboprophylaxis administration. Conversely, all VTE patients should be asked for lung comorbidities before determining anticoagulant therapy duration, as those patients are at increased risk of recurrent PE episodes rather than DVT. Further research is needed to understand the underlying pathophysiology of in-situ thrombosis in those patients.
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Ricci F, Cavallo AU, Luca P, Vincenzo DS, Monia P, D’Errico F, Benelli L, Paola R, Floris R, Chiocchi M. Radiological pitfalls associated with the diagnosis of usual interstitial pneumonia pattern on high-resolution computed tomography and associated findings: experience from a single Italian center. Acta Radiol 2021; 62:619-627. [PMID: 32586124 DOI: 10.1177/0284185120936270] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
BACKGROUND The diagnostic algorithm for idiopathic pulmonary fibrosis (IPF) based on high-resolution computed tomography (HRCT) findings and multidisciplinary discussion (MDD) has been well established. PURPOSE To identify the causes of disagreement between non-thoracic and thoracic radiologist involved in MDD for the imaging diagnosis of usual interstitial pneumonia (UIP) patterns and associated findings on HRCT and to improve the understanding of IPF by non-expert radiologists through a more systematic approach to HRCT. MATERIAL AND METHODS This study included 68 patients who underwent MDD for suspected IPF. We compared the first reports generated before MDD by non-expert radiologists with the CT pattern and associated findings of IPF reported by thoracic radiologist involved in MDD. RESULTS Regarding the diagnosis of CT pattern by non-expert radiologists, 30/68 patients received a discordant diagnosis, and in another 28 reports, all features of the CT pattern were described without reaching a diagnostic conclusion. The first report was concordant in only 10 patients. For 63 cases in which associated findings were reported by expert radiologists in MDD, we documented discrepancies in 47 cases where associated findings were considered absent by the first non-thoracic radiologist. CONCLUSION We found significant discrepancies in the imaging diagnosis of UIP patterns and associated findings on HRCT between non-expert and thoracic radiologists included in MDD. Therefore, in this study, we analyzed and suggested diagnostic strategies to improve non-expert radiologists' approach to HRCT.
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Affiliation(s)
- Francesca Ricci
- Department of Biomedicine and Prevention, Division of Diagnostic Imaging, University of Rome “Tor Vergata,” Rome, Italy
| | - Armando Ugo Cavallo
- Department of Biomedicine and Prevention, Division of Diagnostic Imaging, University of Rome “Tor Vergata,” Rome, Italy
| | - Pugliese Luca
- Department of Biomedicine and Prevention, Division of Diagnostic Imaging, University of Rome “Tor Vergata,” Rome, Italy
| | - De Stasio Vincenzo
- Department of Biomedicine and Prevention, Division of Diagnostic Imaging, University of Rome “Tor Vergata,” Rome, Italy
| | - Pasqualetto Monia
- Department of Biomedicine and Prevention, Division of Diagnostic Imaging, University of Rome “Tor Vergata,” Rome, Italy
| | - Francesca D’Errico
- Department of Biomedicine and Prevention, Division of Diagnostic Imaging, University of Rome “Tor Vergata,” Rome, Italy
| | - Leonardo Benelli
- Department of Biomedicine and Prevention, Division of Diagnostic Imaging, University of Rome “Tor Vergata,” Rome, Italy
| | - Rogliani Paola
- Respiratory Medicine, Department of Systems Medicine, University of Rome “Tor Vergata,” Rome, Italy
| | - Roberto Floris
- Department of Biomedicine and Prevention, Division of Diagnostic Imaging, University of Rome “Tor Vergata,” Rome, Italy
| | - Marcello Chiocchi
- Department of Biomedicine and Prevention, Division of Diagnostic Imaging, University of Rome “Tor Vergata,” Rome, Italy
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Vargas-Ramírez LK, Cano-Rosales DJ, Bolívar-Aguilar IC, Vásquez-Cardona LM, Rodríguez-Corredor LC, Porras-Bueno CO, Berdugo-Pereira EM. Radiological and histological characteristics of patients with interstitial lung disease undergoing lung biopsy in a reference institution from eastern Colombia. REVISTA DE LA FACULTAD DE MEDICINA 2021. [DOI: 10.15446/revfacmed.v70n1.89890] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
Introduction: Interstitial lung disease (ILD) diagnosis requires a multidisciplinary approach and, in some cases, lung biopsy.
Objective: To describe the sociodemographic and clinical characteristics, as well as the radiological and histological findings, of patients with ILD who required lung biopsy after a multidisciplinary board (pneumology, radiology, and pathology) of a reference center for respiratory diseases in Bucaramanga, Colombia, failed to reach the ILD diagnosis.
Materials and methods: Cross-sectional study. The medical records of 56 patients treated at the Instituto Neumológico del Oriente who underwent lung biopsy between 2015 and 2019 were reviewed. Measures of central tendency and dispersion were calculated for demographic and clinical variables, respectively, to characterize them. A bivariate analysis was performed using Fisher’s exact test to determine whether there were differences in the distribution of the sociodemographic and clinical variables according to the radiological patterns and the final histological diagnosis.
Results: Participants’ median age was 67 years (IQR: 59-72) and 55.35% were men. 43 patients had a radiological pattern inconsistent with usual interstitial pneumonia (UIP); 4 had a pattern consistent with possible UIP; and 9 had a pattern consistent with UIP. The most common histologic diagnoses were hypersensitivity pneumonitis (HP) (32.14%), nonspecific interstitial pneumonia (NSIP) (17.86%), and UIP (19.64%).
Conclusion: In the study population, the primary reason for performing a lung biopsy was the presence of a radiologic pattern inconsistent with UIP, with HP being the predominant histopathological diagnosis. This is the first study to characterize patients with ILD who underwent lung biopsy in eastern Colombia, making a significant contribution to our understanding of the disease’s epidemiology in the country.
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Notarnicola A, Barsotti S, Näsman L, Tang Q, Holmqvist M, Lundberg IE, Antovic A. Evaluation of risk factors and biomarkers related to arterial and venous thrombotic events in idiopathic inflammatory myopathies. Scand J Rheumatol 2021; 50:390-397. [PMID: 33622160 DOI: 10.1080/03009742.2020.1861647] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Objectives: This study aimed to assess the contribution of traditional/disease-related risk factors and biomarkers linked to arterial and venous thrombotic events (TEs) in patients with idiopathic inflammatory myopathies (IIMs).Method: The occurrence of arterial and/or venous TEs at the time of or after IIM diagnosis was retrospectively evaluated in a cohort of 253 patients with IIMs, resulting in a final population of 246 IIM patients, 51 with reported TE (cases) and 195 without a history of TE (comparators). Information on disease characteristics and traditional risk factors for arterial and venous TE (essential hypertension, diabetes, dyslipidaemia, smoking, malignancy) was retrieved. Serum levels of anti-phospholipid antibodies (aPLs) and adhesion molecules were analysed at the time of IIM diagnosis and at the time of the TE in cases.Results: One in five IIM patients (21%) had experienced a TE, arterial TE in 22 and venous TE in 29 patients, with a peak prevalence within 5 years after diagnosis. Among traditional/disease-related risk factors, only older age was associated with both arterial and venous TEs, after adjusting for other covariates. Low serum levels of e-selectin were associated with higher odds of developing a TE, without specific association with either arterial or venous TEs. Only 6% of IIM patients had aPLs, with no significant difference between cases and comparators.Conclusions: An increased risk of both venous and arterial TEs should be considered in IIM patients, particularly close to diagnosis and in elderly people. Low serum levels of e-selectin may predict TE in IIM patients, but the underlying biological mechanism is not known.
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Affiliation(s)
- A Notarnicola
- Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Division of Rheumatology, Karolinska University Hospital, Stockholm, Sweden
| | - S Barsotti
- Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - L Näsman
- Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Division of Rheumatology, Karolinska University Hospital, Stockholm, Sweden
| | - Q Tang
- Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Division of Rheumatology, Karolinska University Hospital, Stockholm, Sweden
| | - M Holmqvist
- Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Division of Rheumatology, Karolinska University Hospital, Stockholm, Sweden.,Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
| | - I E Lundberg
- Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Division of Rheumatology, Karolinska University Hospital, Stockholm, Sweden
| | - A Antovic
- Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Division of Rheumatology, Karolinska University Hospital, Stockholm, Sweden
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Chaudhuri N, George PM, Kreuter M, Molina-Molina M, Rivera-Ortega P, Stella GM, Stewart I, Spencer LG, Wells AU, Jenkins RG. Reply to Althuwaybi et al.: Hospitalization Outcomes for COVID-19 in Patients with Interstitial Lung Disease: A Potential Role for Aerodigestive Pathophysiology? Am J Respir Crit Care Med 2021; 203:522-524. [PMID: 33217244 PMCID: PMC7885838 DOI: 10.1164/rccm.202011-4146le] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Affiliation(s)
| | - Peter M. George
- Imperial CollegeLondon, United Kingdom
- Royal Brompton and Harefield NHS Foundation TrustLondon, United Kingdom
| | - Michael Kreuter
- University of Heidelberg
- German Center for Lung ResearchHeidelberg, Germany
| | | | | | | | - Iain Stewart
- University of NottinghamNottingham, United Kingdom
| | - Lisa G. Spencer
- Liverpool University Hospitals NHS Foundation TrustLiverpool, United Kingdomand
| | - Athol U. Wells
- Royal Brompton and Harefield NHS Foundation TrustLondon, United Kingdom
| | - R. Gisli Jenkins
- University of NottinghamNottingham, United Kingdom
- Nottingham University Hospitals NHS TrustNottingham, United Kingdom
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Gao J, Kalafatis D, Carlson L, Pesonen IHA, Li CX, Wheelock Å, Magnusson JM, Sköld CM. Baseline characteristics and survival of patients of idiopathic pulmonary fibrosis: a longitudinal analysis of the Swedish IPF Registry. Respir Res 2021; 22:40. [PMID: 33546682 PMCID: PMC7866760 DOI: 10.1186/s12931-021-01634-x] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2020] [Accepted: 01/21/2021] [Indexed: 02/08/2023] Open
Abstract
Background Observational data under real-life conditions in idiopathic pulmonary fibrosis (IPF) is scarce. We explored anti-fibrotic treatment, disease severity and phenotypes in patients with IPF from the Swedish IPF Registry (SIPFR). Methods Patients enrolled between September 2014 and April 2020 and followed ≥ 6 months were investigated. Demographics, comorbidities, lung function, composite variables, six-minute walking test (6MWT), quality of life, and anti-fibrotic therapy were evaluated. Agreements between classification of mild physiological impairment (defined as gender-age-physiology (GAP) stage 1) with physiological and composite measures of severity was assessed using kappa values and their impact on mortality with hazard ratios. The factor analysis and the two-step cluster analysis were used to identify phenotypes. Univariate and multivariable survival analyses were performed between variables or groups. Results Among 662 patients with baseline data (median age 72.7 years, 74.0% males), 480 had a follow up ≥ 6 months with a 5 year survival rate of 48%. Lung function, 6MWT, age, and BMI were predictors of survival. Patients who received anti-fibrotic treatment ≥ 6 months had better survival compared to untreated patients [p = 0.007, HR (95% CI): 1.797 (1.173–2.753)] after adjustment of age, gender, BMI, smoking status, forced vital capacity (FVC) and diffusion capacity of carbon monoxide (DLCO). Patients with mild physiological impairment (GAP stage 1, composite physiological index (CPI) ≤ 45, DLCO ≥ 55%, FVC ≥ 75%, and total lung capacity (TLC) ≥ 65%, respectively) had better survival, after adjustment for age, gender, BMI and smoking status and treatment. Patients in cluster 1 had the worst survival and consisted mainly of male patients with moderate-severe disease and an increased prevalence of heart diseases at baseline; Cluster 2 was characterized by mild disease with more than 50% females and few comorbidities, and had the best survival; Cluster 3 were younger, with moderate-severe disease and had few comorbidities. Conclusion Disease severity, phenotypes, and anti-fibrotic treatment are closely associated with the outcome in IPF, with treated patients surviving longer. Phenotypes may contribute to predicting outcomes of patients with IPF and suggest the patients’ need for special management, whereas single or composite variables have some limitations as disease predictors.
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Affiliation(s)
- Jing Gao
- Respiratory Medicine Unit, Department of Medicine, Karolinska Institute, Solna, Solnavägen 30, 17176, Stockholm, Sweden.
| | - Dimitrios Kalafatis
- Respiratory Medicine Unit, Department of Medicine, Karolinska Institute, Solna, Solnavägen 30, 17176, Stockholm, Sweden
| | - Lisa Carlson
- Department of Respiratory Medicine and Allergy, Karolinska University Hospital, Stockholm, Sweden
| | - Ida H A Pesonen
- Respiratory Medicine Unit, Department of Medicine, Karolinska Institute, Solna, Solnavägen 30, 17176, Stockholm, Sweden.,Department of Respiratory Medicine and Allergy, Karolinska University Hospital, Stockholm, Sweden
| | - Chuan-Xing Li
- Respiratory Medicine Unit, Department of Medicine, Karolinska Institute, Solna, Solnavägen 30, 17176, Stockholm, Sweden
| | - Åsa Wheelock
- Respiratory Medicine Unit, Department of Medicine, Karolinska Institute, Solna, Solnavägen 30, 17176, Stockholm, Sweden
| | - Jesper M Magnusson
- Department of Internal Medicine/Respiratory Medicine and Allergology, Institute of Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - C Magnus Sköld
- Respiratory Medicine Unit, Department of Medicine, Karolinska Institute, Solna, Solnavägen 30, 17176, Stockholm, Sweden.,Department of Respiratory Medicine and Allergy, Karolinska University Hospital, Stockholm, Sweden
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Kato S, Kitamura H, Hayakawa K, Fukui K, Tabata E, Otoshi R, Iwasawa T, Utsunomiya D, Kimura K, Tamura K, Ogura T. Coronary artery disease and heart failure in patients with idiopathic pulmonary fibrosis. Heart Vessels 2021; 36:1151-1158. [PMID: 33486554 DOI: 10.1007/s00380-021-01787-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Accepted: 01/15/2021] [Indexed: 10/22/2022]
Abstract
The aim of this study was to investigate the prevalence and prognostic value of coronary artery disease (CAD) and heart failure (HF) in patients with idiopathic pulmonary fibrosis (IPF). Thirteen hundred and fifty-eight patients with interstitial lung disease [851 (62%) males, mean age: 68 ± 10 years] were retrospectively analyzed. CAD was defined as (1) the presence of a clinical diagnosis of angina pectoris, (2) clinical diagnosis of a myocardial infarction, and (3) coronary angiography showing ≥ 1 vessel with a stenosis of > 75%. The definition of HF was made according to the modified Framingham criteria. Compared to the non-IPF group (n = 790), the IPF group (n = 568) had a significantly higher prevalence of CAD (9.3% vs. 4.4%, p < 0.001) and HF (8.2% vs. 3.7%, p < 0.001). During a median follow-up of 1.6 years, 152 deaths were identified. The patients with HF had a significantly worse prognosis than those without HF both in the non-IPF group and IPF group (both p < 0.05). However, the prognosis did not significantly differ between the patients with CAD and those without CAD both in the non-IPF group and IPF group. The presence of HF was an independent predictor of death in the IPF [hazard ratio (HR) 3.67, 95% confidence interval (CI) 1.57-8.56, p = 0.0025] and non-IPF (HR 5.07, 95% CI 1.44-17.86, p = 0.011) patients. The prevalence of CAD and HF was significantly higher in IPF than non-IPF patients. In addition, the presence of HF was a significant prognostic factor for both IPF and non-IPF patients. These results indicated that the importance of HF as a comorbidity for patients with ILD.
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Affiliation(s)
- Shingo Kato
- Department of Cardiology, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Kanagawa, Japan.
| | - Hideya Kitamura
- Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Kanagawa, Japan
| | - Keigo Hayakawa
- Department of Cardiology, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Kanagawa, Japan
| | - Kazuki Fukui
- Department of Cardiology, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Kanagawa, Japan
| | - Erina Tabata
- Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Kanagawa, Japan
| | - Ryota Otoshi
- Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Kanagawa, Japan
| | - Tae Iwasawa
- Kanagawa Cardiovascular and Respiratory Center, Yokohama, Kanagawa, Japan
| | - Daisuke Utsunomiya
- Department of Radiology, Yokohama City University, Yokohama, Kanagawa, Japan
| | - Kazuo Kimura
- Department of Cardiology, Yokohama City University Medical Center, Yokohama, Kanagawa, Japan
| | - Kouichi Tamura
- Department of Medical Science and Cardiorenal Medicine, Yokohama City University, Yokohama, Kanagawa, Japan
| | - Takashi Ogura
- Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Kanagawa, Japan
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45
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Weatherley ND, Eaden JA, Hughes PJC, Austin M, Smith L, Bray J, Marshall H, Renshaw S, Bianchi SM, Wild JM. Quantification of pulmonary perfusion in idiopathic pulmonary fibrosis with first pass dynamic contrast-enhanced perfusion MRI. Thorax 2020; 76:144-151. [PMID: 33273022 PMCID: PMC7815896 DOI: 10.1136/thoraxjnl-2019-214375] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2019] [Revised: 10/02/2020] [Accepted: 10/04/2020] [Indexed: 01/07/2023]
Abstract
Introduction Idiopathic pulmonary fibrosis (IPF) is a fatal disease of lung scarring. Many patients later develop raised pulmonary vascular pressures, sometimes disproportionate to the interstitial disease. Previous therapeutic approaches that have targeted pulmonary vascular changes have not demonstrated clinical efficacy, and quantitative assessment of regional pulmonary vascular involvement using perfusion imaging may provide a biomarker for further therapeutic insights. Methods We studied 23 participants with IPF, using dynamic contrast-enhanced MRI (DCE-MRI) and pulmonary function tests, including forced vital capacity (FVC), transfer factor (TLCO) and coefficient (KCO) of the lungs for carbon monoxide. DCE-MRI parametric maps were generated including the full width at half maximum (FWHM) of the bolus transit time through the lungs. Key metrics used were mean (FWHMmean) and heterogeneity (FWHMIQR). Nineteen participants returned at 6 months for repeat assessment. Results Spearman correlation coefficients were identified between TLCO and FWHMIQR (r=−0.46; p=0.026), KCO and FWHMmean (r=−0.42; p=0.047) and KCO and FWHMIQR (r=−0.51; p=0.013) at baseline. No statistically significant correlations were seen between FVC and DCE-MRI metrics. Follow-up at 6 months demonstrated statistically significant decline in FVC (p=0.040) and KCO (p=0.014), with an increase in FWHMmean (p=0.040), but no significant changes in TLCO (p=0.090) nor FWHMIQR (p=0.821). Conclusions DCE-MRI first pass perfusion demonstrates correlations with existing physiological gas exchange metrics, suggesting that capillary perfusion deficit (as well as impaired interstitial diffusion) may contribute to gas exchange limitation in IPF. FWHMmean showed a significant increase over a 6-month period and has potential as a quantitative biomarker of pulmonary vascular disease progression in IPF.
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Affiliation(s)
- Nicholas D Weatherley
- Polaris, Imaging group, Dept IICD, University of Sheffield, Sheffield, UK.,Academic Directorate of Respiratory Medicine, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, Sheffield, UK
| | - James A Eaden
- Polaris, Imaging group, Dept IICD, University of Sheffield, Sheffield, UK
| | - Paul J C Hughes
- Polaris, Imaging group, Dept IICD, University of Sheffield, Sheffield, UK
| | - Matthew Austin
- Polaris, Imaging group, Dept IICD, University of Sheffield, Sheffield, UK
| | - Laurie Smith
- Polaris, Imaging group, Dept IICD, University of Sheffield, Sheffield, UK
| | - Jody Bray
- Polaris, Imaging group, Dept IICD, University of Sheffield, Sheffield, UK
| | - Helen Marshall
- Polaris, Imaging group, Dept IICD, University of Sheffield, Sheffield, UK
| | - Stephen Renshaw
- Academic Directorate of Respiratory Medicine, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, Sheffield, UK
| | - Stephen M Bianchi
- Academic Directorate of Respiratory Medicine, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, Sheffield, UK
| | - Jim M Wild
- Polaris, Imaging group, Dept IICD, University of Sheffield, Sheffield, UK
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M Lambert E, A Wuyts W, Yserbyt J, De Sadeleer LJ. Statins: cause of fibrosis or the opposite? Effect of cardiovascular drugs in idiopathic pulmonary fibrosis. Respir Med 2020; 176:106259. [PMID: 33276250 DOI: 10.1016/j.rmed.2020.106259] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2019] [Revised: 11/11/2020] [Accepted: 11/23/2020] [Indexed: 12/21/2022]
Abstract
BACKGROUND AND OBJECTIVE Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible interstitial lung disease with poor prognosis despite the recent availability of two antifibrotic drugs. Patients are more susceptible to cardiovascular comorbidities. In this study, we aimed to determine the impact of concomitant cardiovascular drugs on disease progression and survival in a modern IPF cohort. METHODS The database of a tertiary referral centre for interstitial lung diseases in Belgium was reviewed for statin, antiaggregant, anticoagulant and metformin therapy. For a study period of four years, we noted both FVC% and DLCO% trajectories along with survival as outcome measurements. RESULTS 323 patients were included of which 45% had at least one cardiovascular comorbidity. 274 (86%) patients received antifibrotic therapy. Statin users (n = 171) displayed significantly slower annual FVC% (difference 2.9%, CI 1.6-4.4, p < 0.001) and DLCO% decline (difference 1.3%, CI 0.24-2.3, p = 0.013). Results for antiaggregant therapy (n = 152) were inconclusive: we found a trend for slower FVC decline (p = 0.098) and a numerically decrease in survival rates (HR 1.63, p = 0.074) in a multivariate Cox analysis. Anticoagulant use (n = 49) showed a trend towards worse DLCO decline (difference -1.3%, CI -2.6 - 0.02, p = 0.055).r Metformin (n = 28) therapy did not affect IPF progression in terms of pulmonary function test evolution or survival. CONCLUSION This retrospective study demonstrated a benefit of statin therapy on IPF progression. Our observations emphasize the need for large clinical trials analysing the effect of statins, as well as other cardiovascular drugs, in the management of IPF patients.
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Affiliation(s)
- Eline M Lambert
- Department of Respiratory Medicine, University Hospitals Leuven, Belgium.
| | - Wim A Wuyts
- Unit for Interstitial Lung Diseases, Department of Respiratory Medicine, University Hospitals Leuven, Belgium
| | - Jonas Yserbyt
- Unit for Interstitial Lung Diseases, Department of Respiratory Medicine, University Hospitals Leuven, Belgium
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Impairment of right ventricular strain evaluated by cardiovascular magnetic resonance feature tracking in patients with interstitial lung disease. Int J Cardiovasc Imaging 2020; 37:1073-1083. [PMID: 33113068 DOI: 10.1007/s10554-020-02079-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Accepted: 10/19/2020] [Indexed: 12/22/2022]
Abstract
OBJECTIVES The aims of this study were to investigate the relationship between pulmonary hypertension (PH) and right ventricular (RV) strain, and to evaluate the prognostic value of RV strain by cardiac magnetic resonance (CMR) feature tracking for patients with interstitial lung disease (ILD). METHODS A total of seventy ILD patients (mean age: 71 ± 8 years, 39 [56%] males) who underwent CMR and right heart catheterization (RHC) were studied. Using a 1.5T magnetic resonance (MR) scanner, steady-state free precession cine MR images encompassing the RV were acquired in all patients and 20 control subjects. RV longitudinal strain were calculated with a feature tracking algorithm. PH was defined as a mean pulmonary artery pressure of more than 20 mmHg at rest and a pulmonary vascular resistance ≥3 Woods unit. RESULTS The RV longitudinal strain was significantly impaired in the ILD patients with PH (n=18) than ILD patients without PH (n=52) (-13.3 ± 5.4% vs. -16.9±5.4%, p=0.048). The RV longitudinal strain differed significantly between the ILD patients without PH and the controls (n=20) (-16.9 ± 5.4% vs. -20.8 ± 6.2%, p=0.002). Five of 70 (7%) patients died within one-year after CMR scan. Area under receiver operating characteristics curve for predicting death was 0.900 (95%CI: 0.800 to 1.000) for RV strain, 0.643 (95%CI: 0.454 to 0.832) for RVEF. CONCLUSIONS Presence of PH was associated with impairment of RV strain, and RV strain could predict short-term mortality in patients with ILD. RV strain by feature tracking might be useful as a non-invasive prognostic marker for patients with ILD.
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King CS, Freiheit E, Brown AW, Shlobin OA, Aryal S, Ahmad K, Khangoora V, Flaherty KR, Venuto D, Nathan SD. Association Between Anticoagulation and Survival in Interstitial Lung Disease: An Analysis of the Pulmonary Fibrosis Foundation Patient Registry. Chest 2020; 159:1507-1516. [PMID: 33075376 DOI: 10.1016/j.chest.2020.10.019] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2020] [Revised: 09/22/2020] [Accepted: 10/11/2020] [Indexed: 10/23/2022] Open
Abstract
BACKGROUND Aberrations in the coagulation system have been implicated in the pathogenesis of interstitial lung disease (ILD). Anticoagulants have been proposed as a potential therapy in ILD; however, a randomized controlled trial examining warfarin as a treatment for IPF was terminated early due to increased death rates. This has led some to speculate that warfarin specifically may be harmful in ILD, and use of direct oral anticoagulants (DOACs) could result in superior outcomes. RESEARCH QUESTION The goal of this study was to delineate the relationship between anticoagulation and outcomes in patients with ILD through an analysis of the Pulmonary Fibrosis Foundation Patient Registry. STUDY DESIGN AND METHODS An analysis of all patients in the Pulmonary Fibrosis Foundation Patient Registry was performed. Patients were stratified into three groups: no anticoagulation, DOAC use, or warfarin use. Survival was analyzed by using both Kaplan-Meier curves and Cox proportional hazards models. RESULTS Of 1,911 patients included in the analysis, 174 (9.1%) were given anticoagulants; 93 (4.9%) received DOACs, and 81 (4.2%) received warfarin. There was a twofold increased risk of death or transplant for patients receiving DOACS; for warfarin, the risk was over two and half times greater. DOACs were not associated with an increased risk of mortality following adjustment for confounding variables. However, even after adjustment, patients given the anticoagulant warfarin remained at increased risk of mortality. In patients with IPF, warfarin was associated with reduced transplant-free survival, but DOACs were not. There was no statistically significant difference in survival between those receiving warfarin and those receiving a DOAC. INTERPRETATION The need for anticoagulation is associated with an increased risk for death or transplant in patients with ILD, in both the IPF and non-IPF population. Further research is required to determine if warfarin and DOACs present varying safety profiles in patients with ILD.
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Affiliation(s)
- Christopher S King
- Advanced Lung Disease and Transplant Clinic, Inova Fairfax Hospital, Falls Church, VA.
| | - Elizabeth Freiheit
- Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI
| | - A Whitney Brown
- Advanced Lung Disease and Transplant Clinic, Inova Fairfax Hospital, Falls Church, VA
| | - Oksana A Shlobin
- Advanced Lung Disease and Transplant Clinic, Inova Fairfax Hospital, Falls Church, VA
| | - Shambhu Aryal
- Advanced Lung Disease and Transplant Clinic, Inova Fairfax Hospital, Falls Church, VA
| | - Kareem Ahmad
- Advanced Lung Disease and Transplant Clinic, Inova Fairfax Hospital, Falls Church, VA
| | - Vikramjit Khangoora
- Advanced Lung Disease and Transplant Clinic, Inova Fairfax Hospital, Falls Church, VA
| | - Kevin R Flaherty
- Division of Pulmonary & Critical Care Medicine, University of Michigan, Ann Arbor, MI
| | - Drew Venuto
- Advanced Lung Disease and Transplant Clinic, Inova Fairfax Hospital, Falls Church, VA
| | - Steven D Nathan
- Advanced Lung Disease and Transplant Clinic, Inova Fairfax Hospital, Falls Church, VA
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49
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Marks-Garber K, Bdolah-Abram T, Nusair S. Cluster analysis based clinical profiling of Idiopathic Pulmonary Fibrosis patients according to comorbidities evident prior to diagnosis: a single-center observational study. Eur J Intern Med 2020; 80:18-23. [PMID: 32527611 DOI: 10.1016/j.ejim.2020.05.023] [Citation(s) in RCA: 5] [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: 01/27/2020] [Revised: 05/10/2020] [Accepted: 05/14/2020] [Indexed: 01/05/2023]
Abstract
BACKGROUND The characterization and clinical profiling of people affected by Idiopathic Pulmonary Fibrosis (IPF), based on clinical events occurring prior to the diagnosis of the fibrotic disease, may facilitate the understanding of events and comorbidities that occur before the diagnosis of IPF and aid in identifying patients at an earlier stage of the disease. METHODS In this observational study, a cohort of 96 patients, obtained from a community-based pulmonary clinic, were studied retrospectively. These patients were diagnosed with IPF between January 2008 and November 2016, based on findings on lung biopsy and/or high-resolution CT. Using clinical data obtained within the five years before diagnosis and the two-step method of cluster analysis, patients were assigned to one of four groups. The distribution of clinical characteristics and comorbidities present prior to diagnosis was analyzed among the clusters. RESULTS Cluster 1 is composed of male patients, smokers, with ischemic heart disease. Cluster 2 is composed of male patients, smokers with dyspnea at rest, dry cough and prevalent emphysema. Cluster 3 is composed of male patients without other significant comorbidities, half of whom had dyspnea at exertion. Cluster 4 includes female patients only, most of whom never-smokers and the largest portion of patients with hypothyroidism. The majority of patients had basal end-inspiratory crackles at time of diagnosis, equally distributed among clusters. CONCLUSION Different clinical phenotypes of IPF emerge years before time of diagnosis and if confirmed in larger cohorts may help in forming diagnostic algorithms that would allow earlier diagnosis of IPF.
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Affiliation(s)
- Keren Marks-Garber
- Rokach Center for the Prevention of Lung Diseases, Clalit Health Services, Jerusalem Region, Affiliated to The Faculty of Medicine, Hebrew University and Hadassah, Jerusalem, Israel; The Faculty of Medicine, Hebrew University and Hadassah, Jerusalem, Israel
| | - Tali Bdolah-Abram
- The Faculty of Medicine, Hebrew University and Hadassah, Jerusalem, Israel
| | - Samir Nusair
- Rokach Center for the Prevention of Lung Diseases, Clalit Health Services, Jerusalem Region, Affiliated to The Faculty of Medicine, Hebrew University and Hadassah, Jerusalem, Israel; Institute of Pulmonary Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
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50
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González-Meléndez A, Fred-Jiménez RM, Arroyo-Ávila M, Díaz-Correa L, Pérez-Ríos N, Rodríguez N, Ríos G, Vilá LM. Incident arterial vascular events in a cohort of Puerto Ricans with rheumatoid arthritis. SAGE Open Med 2020; 8:2050312120958844. [PMID: 32974020 PMCID: PMC7495931 DOI: 10.1177/2050312120958844] [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: 12/19/2019] [Accepted: 08/25/2020] [Indexed: 11/16/2022] Open
Abstract
Objective The increased morbidity and mortality associated with cardiovascular events in patients with rheumatoid arthritis has been linked to traditional and nontraditional factors. However, these factors vary among different ethnicities. Few studies have described these features in Hispanic populations. Thus, we determined the clinical correlates of arterial vascular events in Hispanics from Puerto Rico. Methods A cross-sectional study was performed in a cohort of 405 Puerto Ricans with rheumatoid arthritis. Demographic parameters, health-related behaviors, clinical manifestations, disease activity (per Disease Activity Score 28), functional status (per Health Assessment Questionnaire), comorbidities, and pharmacotherapy were compared in patients with and without incident arterial vascular events. The latter was defined as the occurrence of myocardial infarction, angina pectoris, vascular procedures for coronary artery disease, stroke, or peripheral artery disease. Study groups were analyzed using bivariate and multivariate analyses. Results Of the total study population, 87.2% were woman. The mean age at study visit was 56.1 ± 13.9 years, and the mean disease duration was 15.0 ± 13.2 years. Arterial vascular events occurred in 43 patients (10.6%). In the multivariate analysis adjusted for age and sex, arterial hypertension, dyslipidemia, metabolic syndrome, extra-articular manifestations, higher Health Assessment Questionnaire score, and number of hospitalizations were associated with arterial cardiovascular events. Conclusion In this cohort of Puerto Ricans with rheumatoid arthritis, traditional and nontraditional factors, particularly extra-articular manifestations and functional disability, were associated with arterial vascular events. Awareness of these associations may help to implement clinical strategies in this group of rheumatoid arthritis patients at risk of arterial vascular events.
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Affiliation(s)
- Ariana González-Meléndez
- Division of Rheumatology, Department of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico
| | - Ruth M Fred-Jiménez
- Division of Rheumatology, Department of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico
| | - Mariangelí Arroyo-Ávila
- Division of Rheumatology, Department of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico
| | - Leyda Díaz-Correa
- Division of Rheumatology, Department of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico
| | - Naydi Pérez-Ríos
- Puerto Rico Clinical and Translational Research Center, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico
| | - Noelia Rodríguez
- Division of Rheumatology, Department of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico
| | - Grissel Ríos
- Division of Rheumatology, Department of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico
| | - Luis M Vilá
- Division of Rheumatology, Department of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico
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