Humidifier lung and summer-type hypersensitivity pneumonitis in Japan: a nationwide retrospective observational study of clinical, radiological and pathological features

Background Humidifier lung (HFL) is a rare subtype of hypersensitivity pneumonitis (HP); understanding of the clinical, radiological and pathological characteristics is limited. To clarify the phenotype of HFL, this study compared HFL with the more established summer-type HP (SHP). Methods This nationwide survey of patients with HFL was conducted in 214 participating facilities across Japan from January 2011 to December 2021. Clinical, radiological and histopathological findings were comparatively evaluated between patients diagnosed with HFL and those with SHP. Results Overall, 430 HFL and 784 SHP cases were identified, with an increasing trend over time and a marked rise in HFL during the COVID-19 pandemic. Detailed data from 278 HFL and 220 SHP cases showed that HFL patients were older and predominantly male. HFL exhibited higher serum C-reactive protein levels but lower Krebs von den Lungen-6 (KL-6) and surfactant protein D levels than SHP (all p<0.0001). Chest CT in both cohorts included ground-glass opacities and mosaic attenuation; centrilobular ground-glass nodules were less frequent in HFL, which more frequently showed airspace consolidation. Histopathology demonstrated alveolitis in both with more intra-alveolar organisation and fewer epithelioid cell granulomas in HFL. Cluster analysis identified an HFL cluster with either Acute Respiratory Distress Syndrome (ARDS)-like or organising pneumonia-like high-resolution CT findings and normal KL-6, hence diagnosis can be challenging. Conversely, the major cluster of SHP showed typical CT features and elevated KL-6. Conclusions HFL exhibits distinct clinical, radiological and pathological characteristics compared to SHP, suggesting a unique subtype. This holds relevance for diagnostic accuracy and improved patient outcomes.