Impact of older age on prognosis in hypersensitivity pneumonitis: A systematic review and meta-analysis.

Abstract

Hypersensitivity pneumonitis (HP) is a heterogeneous immune-mediated interstitial lung disease with markedly variable clinical outcomes. Increasing age has been repeatedly suggested as a determinant of worse prognosis; however, to the best of our knowledge, its independent prognostic impact has not been systematically quantified. A systematic review and meta-analysis were conducted in the present study in accordance with PRISMA guidelines and registered in PROSPERO (CRD420251004649). Medline, Google Scholar and Cochrane databases were searched from 1980 to 2025 for studies evaluating the association between older age and adverse outcomes in HP. Eligible studies included adult HP populations with comparative age data and reported prognostic outcomes, including mortality, rapid forced vital capacity decline, respiratory failure and need for long-term oxygen therapy. A random-effects model was applied, and heterogeneity was assessed using the I² statistic. A total of six observational studies comprising 1,518 patients with HP were included. Across studies, older age consistently associated with poorer outcomes, including increased mortality, higher likelihood of fibrotic disease and greater risk of respiratory failure. In studies reporting age as a continuous variable, pooled analysis demonstrated that each additional year of age was associated with a 5.4% increase in the hazard of death (pooled hazard ratio=1.054; 95% CI 1.030-1.079), with moderate heterogeneity (I²=36.4%); sensitivity analyses confirmed the robustness of the findings. Advanced age is a significant adverse prognostic factor in HP, independently associated with increased mortality and disease progression. These findings support the incorporation of age into prognostic models and risk stratification strategies and highlight the need for age-adapted diagnostic vigilance and individualized management approaches in older patients with HP.