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.

BackgroundIdiopathic pulmonary fibrosis (IPF) is a disease with poor prognosis mainly affecting males. Differences in clinical presentation between genders may be important both for the diagnostic work-up and for follow-up. In the present study, we therefore explored potential gender differences at presentation in a Swedish cohort of IPF-patients.MethodsWe studied patients included in the Swedish IPF- registry over a three-year period from its launch in 2014. A cross-sectional analysis was performed for data concerning demographics, lung function, 6- min walking test (6MWT) and quality of life (QoL) (King’s Brief Interstitial Lung Disease (K-BILD) score).ResultsThree hundred forty- eight patients (250 (72%) males, 98 (28%) females, median age 72 years in both genders) were included in the registry during the study period. Smoking history (N = 169 (68%) vs. N = 53 (54%), p < 0.05), baseline lung function (Forced vital capacity, % of predicted (FVC%): 68.9% ± 14.4 vs. 73.0% ± 17.7, p < 0.05; Total lung capacity, % of predicted (TLC%): 62.2% ± 11.8 vs. 68.6% ± 11.3%, p < 0.001) were significantly different at presentation between males and females, respectively. Comorbidities such as coronary artery disease (OR: 3.5–95% CI: 1.6–7.6) and other cardiovascular diseases (including atrial fibrillation and heart failure) (OR: 3.8–95% CI: 1.9–7.8) also showed significant differences between the genders. The K- BILD showed poor quality of life, but no difference was found between genders in total score (54 ± 11 vs. 54 ± 10, p = 0.61 in males vs. females, respectively).ConclusionsThis study shows that female patients with IPF have a more preserved lung function than males at inclusion, while males have a significant burden of cardiovascular comorbidities. However, QoL and results on the 6MWT did not differ between the groups. These gender differences may be of importance both at diagnosis and follow- up of patients with IPF.

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Background and objective: Antifibrotic therapy with nintedanib or pirfenidone slows disease progression and reduces mortality in patients with idiopathic pulmonary fibrosis (IPF). However, patients with advanced IPF, as defined by forced vital capacity (FVC) < 50% and/or diffusion capacity for carbon monoxide (DLCO) < 30% of predicted, have not been included in randomized trials, and the outcomes of such patients who initiate treatment are not well understood. We determined lung function, disease progression and mortality outcomes following initiation of antifibrotic therapy in patients with advanced IPF at the time of treatment initiation compared to those with mild-moderate IPF. Methods: We included 502 patients enrolled in IPF registries from four Nordic countries. Linear mixed models were used to assess change in FVC and DLCO over time. Cox proportional hazards models were used to assess transplant-free survival and progression-and transplant-free survival. Results: Of 502 patients, 66 (13%) had advanced IPF. Annual change in FVC was À125 ml (95% CI À163, À87) among patients with mild-moderate IPF, and +28 ml (95% CI À96, +152) among those with advanced IPF. Advanced IPF at treatment initiation was associated with poorer transplant-free survival (hazard ratio [HR] 2.39 [95% CI 1.66, 3.43]) and progression-and transplant-free survival (HR 1.60 [95% CI 1.15, 2.23]). Conclusion: In a broadly representative IPF population, patients with advanced IPF at the initiation of antifibrotic therapy did not have greater lung function decline over time compared with those with mild-moderate IPF, but had substantially higher mortality. Prospective studies are needed to determine the effect of antifibrotic therapy in patients with advanced IPF.

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with an unmet need of biomarkers that can aid in the diagnostic and prognostic assessment of the disease and response to treatment. In this two-part explorative proteomic study, we demonstrate how proteins associated with tissue remodeling, inflammation and chemotaxis such as MMP7, CXCL13 and CCL19 are released in response to aberrant extracellular matrix (ECM) in IPF lung. We used a novel ex vivo model where decellularized lung tissue from IPF patients and healthy donors were repopulated with healthy fibroblasts to monitor locally released mediators. Results were validated in longitudinally collected serum samples from 38 IPF patients and from 77 healthy controls. We demonstrate how proteins elevated in the ex vivo model (e.g., MMP7), and other serum proteins found elevated in IPF patients such as HGF, VEGFA, MCP-3, IL-6 and TNFRSF12A, are associated with disease severity and progression and their response to antifibrotic treatment. Our study supports the model’s applicability in studying mechanisms involved in IPF and provides additional evidence for both established and potentially new biomarkers in IPF.