Prevalence, Risk Factors, and Outcomes of Adult Interstitial Lung Abnormalities: A Systematic Review and Meta-Analysis

Abstract

Rationale: Incidental parenchymal abnormalities detected on chest computed tomography scans are termed interstitial lung abnormalities (ILAs). ILAs may represent early interstitial lung disease (ILD) and are associated with an increased risk of progressive fibrosis and mortality. The prevalence of ILAs is unknown, with heterogeneity across study populations. Objectives: Estimate the pooled prevalence of ILAs in lung cancer screening, general population-based, and at-risk familial cohorts using meta-analysis; identify variables associated with ILA risk; and characterize ILA-associated mortality. Methods: The study protocol was registered on PROSPERO (CRD42022373203), and Meta-analyses of Observational Studies in Epidemiology recommendations were followed. Relevant studies were searched on Embase and Medline. Study titles were screened and abstracts reviewed for full-text eligibility. Random effect models were used to pool prevalence estimates for specified subgroups and ILA-associated mortality risk. Risk of ILAs was estimated based on age, sex, and FVC. Quality assessment was conducted using an adapted Assessment Tool for Prevalence Studies. Measurements and Main Results: The search identified 9,536 studies, with 22 included, comprising 88,325 participants. The pooled ILA prevalence was 7% (95% confidence interval [CI], 0.01-0.13) in lung cancer screening, 7% (95% CI, 0.04-0.10) in general population, and 26% (95% CI, 0.20-0.32) in familial cohorts. Pooled mortality risk was increased in those with ILAs (odds ratio, 3.56; 95% CI, 2.19-5.81). Older age, male sex, and lower FVC% were associated with greater odds of ILA. Conclusions: Populations undergoing imaging for non-ILD indications demonstrate high ILA prevalence. Standardized reporting and follow-up of ILAs is needed, including defining those at greatest risk of progression to ILD.

Keywords: ILAs; familial pulmonary fibrosis; interstitial lung disease; lung cancer screening.

Figure 1.

Flow diagram of search progress, as per PRISMA guidelines.

Figure 2.

Pooled prevalence of interstitial lung abnormalities. (A) LCS. (B) GP. (C) FC. AGES = Age, Gene/Environment Susceptibility; CI = confidence interval; ES = effect size; FC = at-risk familial cohort; FHS = Framingham Heart Study; GP = general population cohort; LCS = lung cancer screening cohort.

Figure 2.

Pooled prevalence of interstitial lung abnormalities. (A) LCS. (B) GP. (C) FC. AGES = Age, Gene/Environment Susceptibility; CI = confidence interval; ES = effect size; FC = at-risk familial cohort; FHS = Framingham Heart Study; GP = general population cohort; LCS = lung cancer screening cohort.

Figure 3.

Patient-specific variables associated with interstitial lung abnormality (ILA) risk. (A) Age. (B) Male sex. (C) FVC% predicted. Studies marked (A) indicate meta-analysis of “no ILA” demographic data; studies marked (B) indicate meta-analysis of “indeterminate for ILA” data. CI = confidence interval; FC = at-risk familial cohort; FHS = Framingham Heart Study; GP = general population cohort; IV = inverse variance; LCS = lung cancer screening cohort; M–H = Mantel-Haenszel.

Figure 4.

Association of ILAs and all-cause mortality. CI = confidence interval; FC = at-risk familial cohort; FHS = Framingham Heart Study; GP = general population cohort; ILAs = interstitial lung abnormalities; LCS = lung cancer screening cohort; M–H = Mantel-Haenszel.