The Burden of Progressive-Fibrosing Interstitial Lung Diseases

Abstract

Despite conventional treatment, a proportion of interstitial lung disease (ILD) patients develop a progressive phenotype known as "fibrosing ILD with a progressive phenotype" (PF-ILD), characterized by worsening respiratory symptoms, decline in lung function, and early mortality. This review describes the epidemiology, and the humanistic and economic burden of PF-ILDs other than idiopathic pulmonary fibrosis (non-IPF PF-ILD). A structured review of the literature was conducted, using predefined search strategies in Ovid MEDLINE and EMBASE, and supplemented with gray literature searches. The search identified 3,002 unique articles and an additional 3 sources were included from the gray literature; 21 publications were included. The estimated prevalence of non-IPF PF-ILD ranges from 6.9 to 70.3/100,000 persons and the estimated incidence from 2.1 to 32.6/100,000 person-years. Limited evidence demonstrates that PF-ILD has a significant impact on patients' quality of life, affecting their daily lives, psychological well-being, careers, and relationships. PF-ILD is also associated with significant economic burden, demonstrating higher healthcare resource use and direct costs compared with the non-progressive phenotype, and indirect costs, which include job losses. This review indicates that PF-ILD places a considerable humanistic burden on both patients and caregivers, and a substantial economic burden on healthcare systems, patients, and society.

Keywords: economic burden; epidemiology; humanistic burden; progressive fibrosing ILD; quality of life; survival.

Figure 1

Flow diagram of study inclusion. *Some articles overlapped in their datasets.

Figure 2

Non-IPF PF-ILD (A) prevalence and (B) incidence. *Estimates vary by country; the lower number represents the minimum PPV adjusted value and the higher number the crude maximum value. PPV is based on whether fibrosing ILDs were actually fibrosing ILDs; ^†Age- and sex-adjusted (standardized to the 2014 US Census estimates) ^§Algorithms for definition of progression were specifically designed for each study; see Table 1 for further algorithm details. EU, European Union; PAS, post-authorization study; PF-ILD, progressive fibrosing interstitial lung disease; PPV, positive predictive value.

Figure 3

Proportions of non-IPF fibrosing ILDs with progressive phenotype (%). *In the INBUILD trial, patients were defined as progressive when ≥1 of the following criteria: Relative decline of ≥10% in FVC% predicted OR relative decline ≥5–<10% in FVC% predicted with worsening respiratory symptoms and/or increasing fibrosis on chest imaging OR worsening respiratory symptoms and increasing fibrosis on chest imaging; ^†Pulmonology visit frequency = (≥4 visits in 2016, or ≥3 more visits in 2016 vs. 2014); ^‡Algorithms for definition of progression were specifically designed for each study; see Table 1 for further algorithm details. ^§Pulmonary function decline = (a relative decline of ≥10% in FVC per 24 months or the relative decline in FVC of ≥5% with decline in DLco of ≥15% per 24 months). Light vs. Dark colors on the same bar represent the percentage range (minimum to maximum proportions reported). DLco, diffusing capacity of the lungs for carbon monoxide; EU, European Union; FVC, forced vital capacity; ILD, interstitial lung disease; PAS, post-authorization study; PF-ILD, progressive fibrosing interstitial lung disease.