Progressive Fibrosing Interstitial Lung Disease: Prevalence and Characteristics

interstitial pulmonary fibrosis
What characterizes the progressive fibrosing ILD phenotype, and what baseline factors associated with this phenotype may help guide clinical decision making?

A real-world study found that progression of fibrotic interstitial lung disease (ILD) occurs in approximately 50% of patients at 24 months, and that increasing age, male sex, a history of reflux, and various measures of lung function are associated with progression. Study findings were recently published in the European Respiratory Journal.

The real-world prevalence and features of progressive fibrosing ILD (PF-ILD) is uncertain, although the disease is known to be characterized by progressive physiologic, symptomatic, and/or radiologic worsening. Investigators therefore sought to explore the real-world prevalence and features of PF-ILD using data from the Canadian Registry for Pulmonary Fibrosis (CARE-PF), a cohort of patients with fibrotic ILD of any subtype recruited from 8 specialized ILD centers from 2015 and 2020. The registry defined PF-ILD as: (1) a relative forced vital capacity (FVC) decline of 10% or more; (2) death; (3) lung transplantation; or (4) any 2 of the following within 24 months of diagnosis: relative FVC decline of at least 5% and less than 10%; worsening respiratory symptoms; or worsening fibrosis on chest computed tomography.

Among a total of 2746 participants with fibrotic ILD, 50% (1376 of 2746) met PF-ILD criteria in the initial 24 months of follow-up. Overall, 51% of the patients were female; the mean participant age was 65±12 years. PF-ILD was reported in 59% of patients with IPF, 58% of those with fibrotic hypersensitivity pneumonitis (HP), 51% of participants with unclassified ILD (U-ILD), and 45% of those with connective tissue disease–associated ILD (CTD-ILD).

Compared with patients with IPF, time to disease progression was similar among those with HP (hazard ratio [HR], 0.96; 95% CI, 0.79-1.17), but was delayed in participants with U-ILD (HR, 0.82; 95% CI, 0.71-0.96) and in those with CTD-ILD (HR, 0.65; 95% CI, 0.56-0.74).

Across the various diagnostic subtypes, background treatment varied, with 66% of patients with IPF receiving antifibrotic agents, whereas 49%, 61%, and 37% of patients with chronic HP, CTD-ILD, and U-ILD, respectively, received immunomodulatory therapy. Male sex, increasing age, lower baseline pulmonary function, and the presence of gastroesophageal reflux disease were all independently associated with disease progression.

“Progression of fibrotic ILD, as defined by clinical, radiographic, and physiologic criteria, occurs in approximately 50% patients at 24 months, with the highest rates in those with IPF and HP, followed by U-ILD and CTD-ILD,” the investigators concluded. They further noted that routinely obtained variables — including increasing age, male sex, a history of gastroesophageal reflux disease, baseline FVC below 70% predicted, and DLCO below 75% predicted — can aid in the identification of patients who are at risk for disease progression and may help to guide therapeutic approaches.

The results of the current study are limited by factors that are related mostly to the utilization of registry data. Notably, 219 patients were excluded from the study because of the unavailability of data regarding disease progression within 2 years of being diagnosed with ILD. Because these missing data were balanced across the various diagnostic subgroups, they are less likely to bias comparisons of risk progression with any particular ILD diagnosis.

The investigators stressed the need for future studies identifying additional risk factors for disease progression, such as genetic and molecular profiles, in order to better characterize the risk in individual patients and further inform management decisions.

Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Hambly N, Farooqi MM, Dvorkin-Gheva A, et al. Prevalence and characteristics of progressive fibrosing interstitial lung disease in a prospective registry. Eur Respir J. Published online March 10, 2022. doi:10.1183/13993003.02571-2021