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).
Supported by NHLBI RO1 HL63117 and NO1HR76101-19.
Conflict of Interest Statement: F.C.S. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. F.J.M. no longer has consulting or Speaker's Bureau activities with Intermune. His declaration covered activities dating to the last calendar year. He is a coinvestigator in the GIPF-007 study. His total compensation with this company has been less than $10,000. His interaction with Actelion has been as principal investigator of the BUILD 1 at the University of Michigan. His personal total compensation is less than $10,000. He has no leadership role in activities for this company. Encysive: He has been a member of the steering committee for a selective endothelin antagonist being investigated in scleroderma-related pulmonary parenchymal disease. Given the potential conflict with IPF NET studies, he has relinquished his role on this steering committee. Co-Therix: He has been a member of the steering committee for an inhaled vasodilator (Iloprost) in IPF-related pulmonary hypertension. This relationship has ended. He has been a member of several advisory boards, CME committees, and the Speaker's Bureau for Pfizer relating exclusively to COPD. His total compensation is greater than $10,000, but less than $20,000. He has been a member of several advisory boards, CME committees, and the Speaker's Bureau for Boehringer Ingelheim relating exclusively to COPD. His total compensation is greater than $10,000, but less than $20,000. He has not been involved with any IPF-related compounds. R.M.R. received lecture fees from Boehringer Ingelheim for six to eight talks at various locations ($10,000). B.J.M. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. G.J.C. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. R.M.C. is Chairman at Glaxo Data Safety Monitoring Board (DSMB). S.A.P. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. F.C. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. H.O.C. received $11,000 in 2003 for serving on an advisory board for GlaxoSmithKline (GSK). In addition, he is the coinvestigator on two multicenter studies sponsored by GSK and has received travel expenses to attend meetings related to the project. He has three contract service agreements with GSK to quantify the CT scans in subjects with COPD. A percentage of his salary between 2003 and 2006 ($15,000/yr) derives from contract funds provided to a colleague, Peter D. Pare, by GSK for the development of validated methods to measure emphysema and airway disease using CT. There is no financial relationship between my industry and the current study. A.S. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. M.E. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. J.D.L. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. J.C.H. has been paid for giving lectures at national and international meetings by Altana, GSK, and AstraZeneca (AZ), and has received approximately $10,000 for this activity. He has also served as a consultant for Altana, GSK, and AZ, and has received approximately $15,000 for this activity. He currently serves as a principal investigator on a 2-year Canadian Institutes of Health Industry–sponsored grant on COPD that was awarded to the University of British Columbia.