Prognostic factors of progressive fibrotic hypersensitivity pneumonitis: a large, retrospective, multicentre, observational cohort study.

Background: Fibrotic hypersensitivity pneumonitis (fHP) is an immune-mediated interstitial lung disease caused by sensitisation to chronic allergen inhalation. This study aimed to determine prognostic indicators of progression and mortality in fHP. Methods: This was a retrospective, multicentre, observational, cross-sectional cohort study of consecutive patients diagnosed with fHP from 1 January 2012 to 31 December 2021. Multivariate Cox regression analyses were used to calculate hazard ratios (HRs) with 95% confidence intervals for predictors of progression and survival. Results: A total of 403 patients were diagnosed with fHP: median (interquartile range) age 66.5 (14.0) years, 51.9% females and 55.1% never-smokers. The cause of fHP was mainly fungal (39.7%) or avian (41.4%). Lung biopsy was performed in 269 cases (66.7%). In the whole cohort the variables that were related to mortality or lung transplant were older age (HR 1.08; p<0.001), percentage predicted forced vital capacity (HR 0.96; p=0.001), lymphocytosis in bronchoalveolar lavage (BAL) (HR 0.93; p=0.001), presence of acute exacerbation during follow-up (HR 3.04; p=0.001) and GAP (gender, age and lung physiology) index (HR 1.96; p<0.01). In the group of biopsied patients, the presence of fibroblastic foci at biopsy (HR 8.39; p<0.001) stands out in multivariate Cox regression analyses as a highly significant predictor for increased mortality or lung transplant. GAP index (HR 1.26; p=0.009), lymphocytosis in BAL (HR 0.97; p=0.018) and age (HR 1.03; p=0.018) are also predictors of progression. Conclusions: The study identified several prognostic factors for progression and/or survival in fHP. The presence of fibroblastic foci at biopsy was a consistent predictor for increased mortality and the presence of lymphocytosis in BAL was inversely related to mortality.

[Highlights of the 55th SEPAR Congress]. / Highlights del 55.° Congreso SEPAR.

The 55th SEPAR Congress was held in Pamplona from 2 to 4 of June 2022. Once again, it was the referral scientific meeting for specialists in pulmonology, thoracic surgery, nursing, physiotherapy, paediatric respiratory diseases and other disciplines involved in respiratory care. The Spanish Society of Pulmonology and Thoracic Surgery showed its national and international leadership in the management of respiratory diseases, which was reflected in a program with an excellent content and a high scientific level. In this review, we offer a summary of some notable aspects covered in six selected areas of interest: pulmonary vascular diseases, non-invasive mechanical ventilation and sleep disorders, asthma, chronic obstructive pulmonary disease (COPD), interstitial lung diseases (ILD), and interventional pulmonolgy and lung transplant.

Intravenous cyclophosphamide improves functional outcomes in interstitial lung disease related to idiopathic inflammatory myopathies.

OBJECTIVE: To compare the efficacy, toxicity and glucocorticoid (GC)-sparing effects of intravenous cyclophosphamide (iv CYC) with other immunosuppressive regimes as the induction treatment for Idiopathic Inflammatory Myopathy-Related Interstitial Lung Disease (IIM-ILD). METHODS: Observational comparative study of patients with IIM-ILD from the EPIMAR and Cruces cohorts. The main efficacy outcome was a 6 to 12-month improvement >10% in the forced vital capacity (FVC) from baseline. RESULTS: Overall, 47 patients were included: 22 (47%) in the CYC group and 25 (53%) in the non-CYC group (32% azathioprine, 28% GC alone, 20% mycophenolate, 16% calcineurin-inhibitors and methotrexate and 4% rituximab). 81% patients were female with a mean age of 50.4 years. FVC improvement was achieved by 64% patients in the CYC group vs. 32% in the non-CYC group (p = 0.03). In the logistic regression model, CYC was identified as the only independent predictor of FVC improvement (OR=3.97, 95% CI 1.07-14.75). Patients in the CYC group received more methyl-prednisolone pulses (MP) (59% vs. 28% in the non-CYC group, p = 0.03), less initial GCs doses >30 mg/d (19% vs. 77%, p = 0.001) and lower 6-month average doses of prednisone (11 mg/d vs. 31.1 mg/d, p = 0.001). CONCLUSION: iv CYC showed better functional outcomes than other immunosuppressants in IIM-ILD. The additional use of MP is likely to potentiate the effects of CYC and allows lowering prednisone doses. Therefore, CYC in combination with MP could be considered as the first line induction therapy in IIM-ILD, without limiting its use to rapidly progressive, life-threatening or refractory disease.

Lung Transplant Improves Survival and Quality of Life Regardless of Telomere Dysfunction.

Introduction: Fibrotic interstitial lung diseases (ILDs) are the first indication for lung transplantation (LT). Telomere dysfunction has been associated with poor post-transplant outcomes. The aim of the study was to evaluate the morbi-mortality and quality of life in fibrotic ILDs after lung transplant depending on telomere biology. Methods: Fibrotic ILD patients that underwent lung transplant were allocated to two arms; with or without telomere dysfunction at diagnosis based on the telomere length and telomerase related gene mutations revealed by whole-exome sequencing. Post-transplant evaluation included: (1) short and long-term mortality and complications and (2) quality of life. Results: Fifty-five percent of patients that underwent LT carried rare coding mutations in telomerase-related genes. Patients with telomere shortening more frequently needed extracorporeal circulation and presented a higher rate of early post-transplant hematological complications, longer stay in the intensive care unit (ICU), and a higher number of long-term hospital admissions. However, post-transplant 1-year survival was higher than 80% regardless of telomere dysfunction, with improvement in the quality of life and oxygen therapy withdrawal. Conclusions: Post-transplant morbidity is higher in patients with telomere dysfunction and differs according to elapsed time from transplantation. However, lung transplant improves survival and quality of life and the associated complications are manageable.

Diagnostic delay of associated interstitial lung disease increases mortality in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a systemic autoimmune disease whose main extra-articular organ affected is the lung, sometimes in the form of diffuse interstitial lung disease (ILD) and conditions the prognosis. A multicenter, observational, descriptive and cross-sectional study of consecutive patients diagnosed with RA-ILD. Demographic, analytical, respiratory functional and evolution characteristics were analyzed to evaluate the predictors of progression and mortality. 106 patients were included. The multivariate analysis showed that the diagnostic delay was an independent predictor of mortality (HR 1.11, CI 1.01-1.23, p = 0.035). Also, age (HR 1.33, 95% CI 1.09-1.62, p = 0.0045), DLCO (%) (HR 0.85, 95% CI 0.73-0.98, p = 0.0246), and final SatO2 (%) in the 6MWT (HR 0.62, 95% CI 0.39-0.99, p = 0.0465) were independent predictor variables of mortality, as well as GAP index (HR 4.65, 95% CI 1.59-13.54, p = 0.0051) and CPI index (HR 1.12, 95% CI 1.03-1.22, p = 0.0092). The withdrawal of MTX or LFN after ILD diagnosis was associated with disease progression in the COX analysis (HR 2.18, 95% CI 1.14-4.18, p = 0.019). This is the first study that highlights the diagnostic delay in RA-ILD is associated with an increased mortality just like happens in IPF.