Published ahead of print on June 7, 2007, doi:10.1164/rccm.200612-1772OC
Am. J. Respir. Crit. Care Med., Volume 176, Number 5, September 2007, 454-459
A more recent version of this article appeared on September 1, 2007
Submitted on December 6, 2006
Accepted on June 5, 2007
Survival Following Lung Volume Reduction in COPD: Insights From Small Airway Pathology
James C Hogg1*, Fanny SF Chu1, Wan C Tan1, Don D Sin1, Sanjay A Patel2, Peter D Pare1, Fernando J Martinez3, Robert M Rogers2, Barry J Make4, Gerard J Criner5, Rueben M Cherniack4, Amir Sharafkhaneh6, James D Luketich2, Harvey O Coxson1, W Mark Elliott1, and Frank C Sciurba2
1 University of British Columbia, iCAPTURE Centre for Cardiovascular and Pulmonary Research, St. Paul's Hospital, Vancouver, BC, Canada,
2 Division of Pulmonary Allergy and Critical Care Medicine, Pittsburgh School of Medicine, Pittsburgh, PA, USA,
3 Division of Pulmonary and Critical Care Medicine, University of Michigan Medical School, Ann Arbor, MI, USA,
4 Division of Pulmonary Sciences and Critical Care Medicine, National Jewish Medical and Research Center, University of Colorado School of Medicine, Denver, CO, USA,
5 Division of Pulmonary and Critical Care Medicine, Temple University School of Medicine, Philadelphia, PA, USA,
6 Baylor College of Medicine, Houston, Texas, USA
* To whom correspondence should be addressed. E-mail: JHogg{at}mrl.ubc.ca.
Objective: To determine the association between small airway pathology and long-term survival following lung volume reduction in COPD and the effect of corticosteroids on this pathology. Methods: Severe (GOLD-3) and very severe (GOLD-4) COPD (n=101) were studied following lung volume reduction surgery (LVRS). Respiratory symptoms, quality of life, pulmonary function, exercise tolerance, chest radiology and corticosteroid treatment status were assessed preoperatively. The severity of luminal occlusion, wall thickening and the presence of small airways containing lymphoid follicles were determined in resected lung tissue. Kaplan-Meier survival analysis and Cox proportional hazards models were used to determine the relationship between survival and small airway pathology. The effect of corticosteroids on this pathology was assessed by comparing treated and untreated groups.
Results: The quartile of subjects with the greatest luminal occlusion, adjusted for covariates died earlier than subjects who had the least occlusion (hazard ratio, 3.28; 95% CI, 1.55 to 6.92; p=0.002). There was a trend toward a reduction in the number of airways containing lymphoid follicles (p=0.051) in those receiving corticosteroids with a statistically significant difference between the control and oral ±inhaled corticosteroid-treated groups (p=0.019). However corticosteroid treatment had no effect on airway wall thickening or luminal occlusion. Conclusion: Occlusion of the small airways by inflammatory exudates containing mucus is associated with early death in severe emphysema treated by LVRS. Corticosteroid treatment dampens the host immune response in these airways by reducing lymphoid follicles without changing wall thickening and luminal occlusion.
Key words: Premature death in COPD, inflammation, airway remodeling, small airway mucosal immune response, corticosteroids
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