Incidence and Progression of Fibrotic Lung Disease in an At-Risk Cohort

Abstract

Rationale: Relatives of patients with familial interstitial pneumonia (FIP) are at increased risk for pulmonary fibrosis and develop preclinical pulmonary fibrosis (PrePF). Objectives: We defined the incidence and progression of new-onset PrePF and its relationship to survival among first-degree relatives of families with FIP. Methods: This is a cohort study of family members with FIP who were initially screened with a health questionnaire and chest high-resolution computed tomography (HRCT) scan, and approximately 4 years later, the evaluation was repeated. A total of 493 asymptomatic first-degree relatives of patients with FIP were evaluated at baseline, and 296 (60%) of the original subjects participated in the subsequent evaluation. Measurements and Main Results: The median interval between HRCTs was 3.9 years (interquartile range, 3.5-4.4 yr). A total of 252 subjects who agreed to repeat evaluation were originally determined not to have PrePF at baseline; 16 developed PrePF. A conservative estimate of the annual incidence of PrePF is 1,023 per 100,000 person-years (95% confidence interval, 511-1,831 per 100,000 person-years). Of 44 subjects with PrePF at baseline, 38.4% subjects had worsening dyspnea compared with 15.4% of those without PrePF (P = 0.002). Usual interstitial pneumonia by HRCT (P < 0.0002) and baseline quantitative fibrosis score (P < 0.001) are also associated with worsening dyspnea. PrePF at the initial screen is associated with decreased survival (P < 0.001). Conclusions: The incidence of PrePF in this at-risk population is at least 100-fold higher than that reported for sporadic idiopathic pulmonary fibrosis (IPF). Although PrePF and IPF represent distinct entities, our study demonstrates that PrePF, like IPF, is progressive and associated with decreased survival.

Keywords: familial idiopathic pulmonary fibrosis; idiopathic pulmonary fibrosis; pulmonary fibrosis.

Figure 1.

Scatterplot of the quantitative data-driven texture analysis fibrosis score comparing changes in score. Individual subjects are color coded according to fibrosis score change between baseline and follow-up. The fibrosis score changes are coded according to >2 SE change (red), score change < 2 SE (green), and score change < −2 SE (blue). Eight subjects were not scored because of technically limited high-resolution computed tomography scan quality.

Figure 2.

Kaplan-Meier plots of survival comparing subjects with preclinical pulmonary fibrosis (PrePF) (cyan) versus no PrePF (pink) as determined by the clinical core. Survival was determined on 492 subjects, because 1 subject had missing identifying information in the database and therefore survival data could not be determined.