Aims

To evaluate the clinical significance of bronchiolocentric fibrosis (BCF) in patients with a histopathological pattern of usual interstitial pneumonia (UIP).

Methods and results

Two hundred and fifty-two patients with pathological UIP pattern were identified. Two hundred and fifteen of these patients (215 of 252) had the multidisciplinary diagnosis of idiopathic pulmonary fibrosis (IPF). Prospectively defined clinical, radiological and pathological features (including BCF) were recorded, and peripheral blood MUC5B genotype and telomere length were measured. BCF was observed in 38% (96 of 252) of all patients and 33% (72 of 215) of IPF patients; its presence was associated with a non-IPF diagnosis on multivariate analysis (odds ratio = 3.71, 95% confidence interval = 1.68-8.19). BCF was not significantly associated with environmental exposures, gastroesophageal reflux, cigarette smoking or radiological patterns. There was no significant association of BCF with MUC5B genotype or telomere length. BCF has no significant impact on survival time.

Conclusions

Most patients with BCF and a histopathological pattern of UIP have IPF. However, this combined fibrotic pattern is associated with a non-IPF multidisciplinary diagnosis, with approximately one-quarter of these patients being diagnosed as chronic hypersensitivity pneumonia or unclassifiable interstitial fibrosis. The presence of BCF in these patients is not significantly associated with presumed clinical risk factors for bronchiolocentric involvement, radiological findings, MUC5B genotype, telomere length or survival time.

Oxidative stress plays a pivotal role in the pathogenesis of asthma. Aquaporin-3 (AQP3) is a small transmembrane water/glycerol channel that may facilitate the membrane uptake of hydrogen peroxide (H2O2). Here we report that AQP3 potentiates ovalbumin (OVA)-induced murine asthma by mediating both chemokine production from alveolar macrophages and T cell trafficking. AQP3 deficient (AQP3(-/-)) mice exhibited significantly reduced airway inflammation compared to wild-type mice. Adoptive transfer experiments showed reduced airway eosinophilic inflammation in mice receiving OVA-sensitized splenocytes from AQP3(-/-) mice compared with wild-type mice after OVA challenge, consistently with fewer CD4(+) T cells from AQP3(-/-) mice migrating to the lung than from wild-type mice. Additionally, in vivo and vitro experiments indicated that AQP3 induced the production of some chemokines such as CCL24 and CCL22 through regulating the amount of cellular H2O2 in M2 polarized alveolar macrophages. These results imply a critical role of AQP3 in asthma, and AQP3 may be a novel therapeutic target.