Background The INBUILD trial investigated the efficacy and safety of nintedanib versus placebo in patients with progressive fibrosing interstitial lung diseases (ILDs) other than idiopathic pulmonary fibrosis (IPF). We aimed to establish the effects of nintedanib in subgroups based on ILD diagnosis. Methods The INBUILD trial was a randomised, double-blind, placebo-controlled, parallel group trial done at 153 sites in 15 countries. Participants had an investigator-diagnosed fibrosing ILD other than IPF, with chest imaging features of fibrosis of more than 10% extent on high resolution CT (HRCT), forced vital capacity (FVC) of 45% or more predicted, and diffusing capacity of the lung for carbon monoxide (DLco) of at least 30% and less than 80% predicted. Participants fulfilled protocol-defined criteria for ILD progression in the 24 months before screening, despite management considered appropriate in clinical practice for the individual ILD. Participants were randomly assigned 1:1 by means of a pseudorandom number generator to receive nintedanib 150 mg twice daily or placebo for at least 52 weeks. Participants, investigators, and other personnel involved in the trial and analysis were masked to treatment assignment until after database lock. In this subgroup analysis, we assessed the rate of decline in FVC (mL/year) over 52 weeks in patients who received at least one dose of nintedanib or placebo in five prespecified subgroups based on the ILD diagnoses documented by the investigators: hypersensitivity pneumonitis, autoimmune ILDs, idiopathic non-specific interstitial pneumonia, unclassifiable idiopathic interstitial pneumonia, and other ILDs. The trial has been completed and is registered with ClinicalTrials.gov, number NCT02999178.

Patient-directed online information on IPF is frequently incomplete, inaccurate, and outdated. There is no reliable method for patients to identify sites that provide appropriate information on IPF.

Acute exacerbation of interstitial lung disease (ILD) is associated with a poor prognosis and high mortality. Numerous studies have documented acute exacerbation in idiopathic pulmonary fibrosis (IPF), but less is known about these events in other ILDs that may present a progressive-fibrosing phenotype. We propose defining acute exacerbation as an acute, clinically significant respiratory deterioration, typically less than 1 month in duration, together with computerised tomography imaging showing new bilateral glass opacity and/or consolidation superimposed on a background pattern consistent with fibrosing ILDs. Drawing on observations in IPF, it is suspected that epithelial injury or proliferation and autoimmunity are risk factors for acute exacerbation in ILDs that may present a progressive-fibrosing phenotype, but further studies are required. Current acute exacerbation management strategies are based on recommendations in IPF, but no randomised controlled trials of acute exacerbation management have been performed. Although there are no formal strategies to prevent the development of acute exacerbation, possible approaches include antifibrotic drugs (such as nintedanib and pirfenidone), and minimising exposure to infection, airborne irritants and pollutants. This review discusses the current knowledge of acute exacerbation of ILDs that may present a progressive-fibrosing phenotype and acknowledges limitations of the data available.

RationaleProgressive fibrosing interstitial lung disease (PF-ILD) is characterised by progressive physiologic, symptomatic, and/or radiographic worsening. The real-world prevalence and characteristics of PF-ILD remain uncertain.MethodsPatients were enrolled from the Canadian Registry for Pulmonary Fibrosis between 2015–2020. PF-ILD was defined as a relative forced vital capacity (FVC) decline ≥10%, death, lung transplantation, or any 2 of: relative FVC decline ≥5 and <10%, worsening respiratory symptoms, or worsening fibrosis on computed tomography of the chest, all within 24 months of diagnosis. Time-to-event analysis compared progression between key diagnostic subgroups. Characteristics associated with progression were determined by multivariable regression.ResultsOf 2746 patients with fibrotic ILD (mean age 65±12 years, 51% female), 1376 (50%) met PF-ILD criteria in the first 24 months of follow-up. PF-ILD occurred in 427 (59%) patients with idiopathic pulmonary fibrosis (IPF), 125 (58%) with fibrotic hypersensitivity pneumonitis (HP), 281 (51%) with unclassifiable ILD (U-ILD), and 402 (45%) with connective tissue disease-associated ILD (CTD-ILD). Compared to IPF, time to progression was similar in patients with HP (hazard ratio [HR] 0.96, 95% confidence interval, CI 0.79–1.17), but was delayed in patients with U-ILD (HR 0.82, 95% CI 0.71–0.96) and CTD-ILD (HR 0.65, 95% CI 0.56–0.74). Background treatment varied across diagnostic subtypes with 66% of IPF patients receiving antifibrotic therapy, while immunomodulatory therapy was utilised in 49%, 61%, and 37% of patients with CHP, CTD-ILD, and U-ILD respectively. Increasing age, male sex, gastroesophageal reflux disease, and lower baseline pulmonary function were independently associated with progression.InterpretationProgression is common in patients with fibrotic ILD, and is similarly prevalent in HP and IPF. Routinely collected variables help identify patients at risk for progression and may guide therapeutic strategies.