Histologic Findings of Severe/Therapy-Resistant Asthma From Video-assisted Thoracoscopic Surgery Biopsies

Abstract

The histologic changes occurring in severe/therapy-resistant asthma (SA) as defined by the European Respiratory Society/American Thoracic Society guidelines, particularly at the level of the distal airways are unknown. This study describes the clinical, radiologic, and histologic characteristics of 29 SA patients who underwent video-assisted thoracoscopic surgery lung biopsy. Pathologic observations were correlated with clinical features, especially the presence of autoimmune disease (AID) (15/29, 51.7%). Ten biopsies (10/29, 34.5%) showed only small airway manifestations of asthma, whereas in 19 (65.5%) asthmatic granulomatosis, manifested by asthmatic bronchiolitis supplemented by an alveolar septal mononuclear infiltrates with non-necrotizing granulomas, was present. SA patients without asthmatic granulomatosis showed more striking small airway injury, subbasement membrane thickening, and neutrophilic infiltrates. Cases with concurrent AID had a tendency to more parenchymal eosinophilic inflammation, more bronchiolocentric granulomas, and a suggestion of increased responsivity to nonsteroidal immunosuppressive therapy. Histologic examination of video-assisted thoracoscopic surgery lung biopsies in SA demonstrates diverse pathologies including cases associated with granulomatous inflammation in addition to eosinophilic infiltrates. This spectrum of histologies may link to a high incidence of AID.

Figure 1

Morphologic findings in the small airways of severe/therapy-resistant asthma (SA). (A) SA case showing mucus plug, goblet cell metaplasia and mixed submucosal predominantly eosinophilic infiltrate. (B) SA with concurrent autoimmune disease (SA-AID) case. (C) Small airways of asthmatic granulomatosis (SA-AG). (D) SA-AG with concurrent autoimmune disease (SA-AG-AID). Small airway demonstrates mucus plug and smooth muscle hypertrophy (hematoxylin and eosin, ×200).

Figure 2

(A) Small airway in severe/therapy-resistant asthma (SA) showing subbasement membrane thickening and neutrophilic inflammation (asterisks). (B) Asthmatic granulomatosis with concurrent autoimmune disease (SA-AG-AID) case showing a patchy interstitial mononuclear infiltrate with eosinophils and lymphocytes (hematoxylin and eosin, ×400).

Figure 3

Severe/therapy-resistant asthma manifesting as asthmatic granulomatosis (SA-AG) showing patchy mononuclear cell infiltrates associated with an ill-defined, poorly formed non-necrotizing granulomas, containing lymphocytes, histiocytes and giant cells, located in the interstitium (A and B) and with bronchiolocentricity in SA-AG with concurrent autoimmune disease (SA-AG-AID) (C and D) (hematoxylin and eosin, ×200).