Small Airway Pathology and Bronchoreversibility in Advanced Emphysema

ABSTRACT

Background: Poorly reversible airflow obstruction is a hallmark feature of chronic obstructive pulmonary disease (COPD). However, some COPD patients demonstrate significant bronchodilator reversibility (BDR). The pathologic features associated with the presence or absence of this phenomenon are not known. Methods: We analyzed 67 patients with advanced upper lobe predominant emphysema who underwent lung volume reduction surgery and divided them into 2 groups: the reversible group [BD(+)] had a >12% and >200 mL increase in FEV₁ or FVC with bronchodilator; the irreversible group [BD(−)] had a ≤12% and ≤20 mL increase in FEV₁ and FVC. We measured the epithelial height (EH) and areas of epithelium (EA), subepithelium (SEA), smooth muscle (SMWA), and total wall (TWA) of the small airways (<2 mm in internal diameter) in the resected specimens, and adjusted these measurements for basement membrane area (BMA) or perimeter (BMP). Results: Despite similar baseline characteristics, the BD(+) group had a smaller EH (0.036 mm vs. 0.042 mm, p = 0.005) and EH/BMP (0.012 vs. 0.014, p = 0.007), and a greater SMWA/BMA (0.491 vs. 0.430, p = 0.034) compared to the BD(−) group. In addition, EA trended to be smaller in the BD(+) group when compared to the BD(−) group (0.160 mm² vs. 0.184 mm², p = 0.06). In a subset of patients with consistent patterns of BDR on serial testing, the BD(+) group had greater SMWA/BMA (0.518 vs. 0.433, p = 0.049) and TWA/BMA (1.405 vs. 1.266, p = 0.036) compared to the BD(−) group. Conclusions: Small airway smooth muscle mass may play a role in determining BDR in severe emphysema.

Keywords: :

• Pulmonary Disease
• Chronic Obstructive / pa (Pathology)
• Airway Remodeling
• Airflow Obstruction
• Human Airway Smooth Muscle
• Bronchodilator Reversibility

ACKNOWLEDGEMENT

This study was partially supported by the 2006 Richard L. Evans Foundation Faculty Development Research Award. VK has participated in clinical trials sponsored by Boehringer Ingelheim, Glaxo-Smith-Kline, and Roche pharmaceuticals. GJC has served on Advisory Committees for Ortho-Biotech, Schering-Plough, Boehringer Ingelheim, Actelion, Shire and Sepracor Pharmaceticals. All of these sums are less than $2,500. GJC has received research grants from: Schering-Plough, Boehringer Ingelheim, Actelion, Glaxo-Smith-Kline, Advanta, Daiichi Asubio, Pfizer, Roche and Sepracor Pharmaceticals, Emphasys Medical, Inc., and Aeris Therapeutics. All research grant monies are deposited and controlled by Temple University. RMP, MA, and JPG claim no financial relationships.

Declaration of interests

The authors have no conflicts of interest to disclose. The authors alone are responsible for the content and writing of the paper.