Characterization of Immunopathology and Small Airway Remodeling in Constrictive Bronchiolitis
Sergey Gutor, Bradley W. Richmond, Rui‐Hong Du, Pingsheng Wu, Jae Woo Lee, Lorraine B. Ware, Ciara M. Shaver, Sergey V. Novitskiy, Joyce E. Johnson, John H. Newman, Stephen I. Rennard, Robert Miller, Timothy S. Blackwell, Vasiliy V. Polosukhin
Abstract
Abstract Rationale Constrictive bronchiolitis (ConB) is a relatively rare and understudied form of lung disease whose underlying immunopathology remains incompletely defined. Objectives Our objectives were to quantify specific pathological features that differentiate ConB from other diseases that affect the small airways and to investigate the underlying immune and inflammatory phenotype present in ConB. Methods We performed a comparative histomorphometric analysis of small airways in lung biopsy samples collected from 50 soldiers with postdeployment ConB, 8 patients with sporadic ConB, 55 patients with chronic obstructive pulmonary disease, and 25 nondiseased control subjects. We measured immune and inflammatory gene expression in lung tissue using the NanoString nCounter Immunology Panel from six control subjects, six soldiers with ConB, and six patients with sporadic ConB. Measurements and Main Results Compared with control subjects, we found shared pathological changes in small airways from soldiers with postdeployment ConB and patients with sporadic ConB, including increased thickness of the smooth muscle layer, increased collagen deposition in the subepithelium, and lymphocyte infiltration. Using principal-component analysis, we showed that ConB pathology was clearly separable both from control lungs and from small airway disease associated with chronic obstructive pulmonary disease. NanoString gene expression analysis from lung tissue revealed T-cell activation in both groups of patients with ConB with upregulation of proinflammatory pathways, including cytokine–cytokine receptor interactions, NF-κB (nuclear factor-κB) signaling, TLR (Toll-like receptor) signaling, T-cell receptor signaling, and antigen processing and presentation. Conclusions These findings indicate shared immunopathology among different forms of ConB and suggest that an ongoing T-helper cell type 1–type adaptive immune response underlies airway wall remodeling in ConB.