Relationship between Pathologic Characteristics of Peripheral Airways and Outcome after Lung Volume Reduction Surgery in Severe Chronic Obstructive Pulmonary Disease

Background: Despite recent advances in the selection process for lung volume reduction surgery (LVRS), there remains significant variability in individual response. Our primary hypothesis was that variations in peripheral airway thickness and/or luminal mucous content contributed to variability in survival after LVRS. We further explored the relationship between these pathologic indices and changes in symptoms and physiology. Methods: Participants included a total of 101 subjects undergoing LVRS as participants in the National Emphysema Treatment Trial (NETT; n = 94) and the University of Pittsburgh LVRS program (n = 7). Small (⩽ 2 mm) airways were isolated from formalin-fixed and paraffin-processed lung specimens using digital-image analysis. Luminal content/maximal luminal area was represented as LC%. Survival was analyzed using uni- and multivariate proportional hazards models. Results: Total airway wall thickness was not a predictor of survival. LC% as a continuous or categorical measure was a strong predictor of survival (⩾ 42% [n = 25] vs. < 42% [n = 74]; hazard ratio [HR], 5.1; p < 0.0001; median survival, 3.2 vs. 6.6 yr), even after adjustments for age, sex, presence of upper lobe predominant emphysema and low exercise capacity and FEV1. Subjects with LC% ⩾ 42% did not differ significantly from those with LC% < 42% in baseline FEV1, RV or maximal exercise watts, cough, sputum, dyspnea, or quality of life (University of California, San Diego, Shortness of Breath; St. George Respiratory Questionnaire [UCSD-SOB; SGRQ]). At 24 months, ΔFEV1, ΔRV, and ΔSGRQ were similar. Subjects with LC% ⩾ 42 had less improvement in watts and dyspnea at 24 months (Δwatts, −7.6 vs. +5 .5; p = 0.03; ΔUCSD-SOB, +1.9 vs. −14.1; p = 0.01). Conclusions: Increased peripheral airway LC% but not airway wall thickness is associated with poorer survival and a greater decline in exercise tolerance and dyspnea in subjects with chronic obstructive pulmonary disease after LVRS independent of established predictors. Notably, LC% was not associated with cough and sputum production. It is not clear whether the prognostic nature of airway luminal mucus is specific to patients undergoing LVRS or reflects the natural history of the disease. Figure 1. Percentage of luminal content (LC%) was a strong predictor of poor survival. Lowest quartile (n = 25) versus upper three quartiles (n = 74; hazard ratio [HR], 5.1; p < 0.0001).