The impact of nintedanib and pirfenidone on lung function and survival in patients with idiopathic pulmonary fibrosis in real-life setting.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic, fibrosing interstitial pneumonia of unknown cause that is associated with radiological and/or histological features of usual interstitial pneumonia (UIP). A mean survival of 2-5 years was reported previously to the advent of antifibrotics. According to clinical trials, nintedanib and pirfenidone induce a significant delay in functional decline, with a favorable impact on survival. METHODS: A real-life retrospective and longitudinal study was conducted to assess the efficacy and tolerability of antifibrotics in IPF patients, between January 2014 and December 2020. Two groups (under nintedanib or pirfenidone) were analyzed at diagnosis through their clinical features and radiological patterns. Lung function was assessed at diagnosis (time 0) and after 6, 12 and 24 months of treatment. We also compared this antifibrotic cohort with an older naïve antifibrotic cohort, mainly treated with immunosuppressive drugs and/or N- acetylcysteine. Survival was analyzed and prognostic features were also studied. Statistical analysis was performed with IBM® SPSS®. RESULTS: A cohort of 108 patients under antifibrotics (nintedanib n = 54; pirfenidone n = 54) was assessed. Lung function analysis showed an overall stabilization in FVC and DLCO mean predicted percentages at 6, 12 and 24 months of treatment. The mean decline in FVC and DLCO, at 12 months, was -40.95 ± 438.26 mL and -0.626 ± 1.31 mL/min/mmHg, respectively. However, during this period, 34.2% of the patients died mostly due to acute exacerbation associated with a poorer lung function at diagnosis. Mean survival in the naïve antifibrotic cohort was significantly lower than in the antifibrotic cohort (39.9 months versus 58.2 months; p < 0.005). Regarding lung function evolution and survival, we found no differences between definitive or probable UIP radiological patterns, both on patients under nintedanib and pirfenidone (p = 0.656). CONCLUSIONS: In this real-life observational study, the positive impact of antifibrotic therapy on the IPF clinical course and on survival was corroborated. Regarding efficacy, there was no difference between patients taking nintedanib or pirfenidone. The need for an early treatment was also demonstrated, since a worse outcome is clearly associated with lower lung volumes and lower diffusing capacity at diagnosis.

Diffuse alveolar hemorrhage: how relevant is etiology?

BACKGROUND: Diffuse Alveolar Hemorrhage (DAH) is a rare and potentially life-threatening clinical syndrome whose early recognition is essential. OBJECTIVES: Characterization of patients with DAH and comparison of presentation and evolution of the disease according to etiology. METHODS: We retrospectively reviewed the clinical records of patients admitted to our hospital over a 7-year period with DAH. Criteria for DAH (1+2): 1 - hemoptysis and/or pulmonary infiltrates and/or anemia (DAH triad); 2 - hemorrhagic bronchoalveolar lavage (BAL) or siderophagic alveolitis. DAH was grouped in immune and nonimmune and the course of disease was compared. RESULTS: We included 24 patients admitted with DAH, of which 11 had an immune cause: p-ANCA vasculitis (n=7), Systemic Lupus Erythematosus (n=2), c-ANCA vasculitis (n=1), Rheumatoid Arthritis (n=1) and 13 had a nonimmune cause: heart disease (n=6), amiodarone toxicity (n=2), clotting disorder (n=2), cannabis toxicity (n=1), S. aureus infection (n=1) and idiopathic (n=1). Patients with nonimmune DAH were significantly older than those with immune DAH (67.9±18.1 vs 56.6±18.8 years, p=0.042). DAH triad was observed in 54% of all patients, hemoptysis in 67%, anemia in 79%, and pulmonary infiltrates in all cases. Patients with immune DAH had more frequently pulmonary-renal syndrome (p<0.001), kidney failure (p=0.048), shock (p=0.049) and needed more frequently admition in ICU (p=0.039) and blood transfusion (p=0.043). Hospital length of stay was superior in immune group (29.5±20.0 vs 19.5±14.3 days, p=0.047). In-hospital mortality was exclusive to immune DAH (12.5%). CONCLUSIONS: Patients with DAH due to immune causes were significantly younger, had more severe presentations of the disease and worst outcomes.