Survival after lung volume reduction in chronic obstructive pulmonary disease: insights from small airway pathology.

RATIONALE COPD is associated with reduced life expectancy. OBJECTIVES To determine the association between small airway pathology and long-term survival after lung volume reduction in chronic obstructive pulmonary disease (COPD) and the effect of corticosteroids on this pathology. METHODS Patients with severe (GOLD-3) and very severe (GOLD-4) COPD (n = 101) were studied after lung volume reduction surgery. 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. MEASUREMENTS AND MAIN 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% confidence interval, 1.55-6.92; 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. CONCLUSIONS Occlusion of the small airways by inflammatory exudates containing mucus is associated with early death in patients with severe emphysema treated by lung volume reduction surgery. Corticosteroid treatment dampens the host immune response in these airways by reducing lymphoid follicles without changing wall thickening and luminal occlusion.

[1]  Bartolome Celli,et al.  Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. , 2007, The New England journal of medicine.

[2]  A. Nissinen,et al.  Thirty-year cumulative incidence of chronic bronchitis and COPD in relation to 30-year pulmonary function and 40-year mortality: a follow-up in middle-aged rural men. , 2006, Chest.

[3]  B. Make,et al.  Relationship between pathologic characteristics of peripheral airways and outcome after lung volume reduction surgery in severe chronic obstructive pulmonary disease. , 2006, Proceedings of the American Thoracic Society.

[4]  B. Make,et al.  Airway and parenchymal disease in chronic obstructive pulmonary disease are distinct phenotypes. , 2006, Proceedings of the American Thoracic Society.

[5]  P. Nilsson,et al.  Mortality in GOLD stages of COPD and its dependence on symptoms of chronic bronchitis , 2005, Respiratory research.

[6]  B. Grant,et al.  Moraxella catarrhalis in chronic obstructive pulmonary disease: burden of disease and immune response. , 2005, American journal of respiratory and critical care medicine.

[7]  Ronnie Driver,et al.  Biostatistics: a Methodology for the Health Sciences , 2005 .

[8]  P. Paré,et al.  The nature of small-airway obstruction in chronic obstructive pulmonary disease. , 2004, The New England journal of medicine.

[9]  T G Clark,et al.  Survival Analysis Part I: Basic concepts and first analyses , 2003, British Journal of Cancer.

[10]  Steven Piantadosi,et al.  A randomized trial comparing lung-volume-reduction surgery with medical therapy for severe emphysema. , 2003, The New England journal of medicine.

[11]  B. Grant,et al.  New strains of bacteria and exacerbations of chronic obstructive pulmonary disease. , 2002, The New England journal of medicine.

[12]  Steven Piantadosi,et al.  Patients at high risk of death after lung-volume-reduction surgery. , 2001, The New England journal of medicine.

[13]  R. Pauwels,et al.  Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop summary. , 2001, American journal of respiratory and critical care medicine.

[14]  J. Nadel,et al.  Relationship of epidermal growth factor receptors to goblet cell production in human bronchi. , 2001, American journal of respiratory and critical care medicine.

[15]  P. Burgel,et al.  Activation of epidermal growth factor receptors is responsible for mucin synthesis induced by cigarette smoke. , 2001, American journal of physiology. Lung cellular and molecular physiology.

[16]  S. Gillespie,et al.  Pathogenesis of pneumococcal infection. , 2000, Journal of medical microbiology.

[17]  P. Burgel,et al.  Relation of epidermal growth factor receptor expression to goblet cell hyperplasia in nasal polyps. , 2000, The Journal of allergy and clinical immunology.

[18]  K. Dabbagh,et al.  Oxidative Stress Causes Mucin Synthesis Via Transactivation of Epidermal Growth Factor Receptor: Role of Neutrophils1 , 2000, The Journal of Immunology.

[19]  K. Dabbagh,et al.  Agarose plug instillation causes goblet cell metaplasia by activating EGF receptors in rat airways. , 2000, American journal of physiology. Lung cellular and molecular physiology.

[20]  R. Kaplan,et al.  Validation of a new dyspnea measure: the UCSD Shortness of Breath Questionnaire. University of California, San Diego. , 1998, Chest.

[21]  L. Fabbri,et al.  Inflammatory cells in the bronchial glands of smokers with chronic bronchitis. , 1997, American journal of respiratory and critical care medicine.

[22]  J. Wedzicha,et al.  Causes of death in patients with COPD and chronic respiratory failure. , 1997, Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace.

[23]  G. Snider,et al.  Elastase causes secretory discharge in bronchi of hamsters with elastase-induced secretory cell metaplasia. , 1993, Experimental lung research.

[24]  P. Jones,et al.  A self-complete measure of health status for chronic airflow limitation. The St. George's Respiratory Questionnaire. , 1992, The American review of respiratory disease.

[25]  A. Dobson An introduction to generalized linear models , 1991 .

[26]  J. Hogg,et al.  The use of the internal perimeter to compare airway size and to calculate smooth muscle shortening. , 1988, The American review of respiratory disease.

[27]  J. Hogg,et al.  Reassessment of inflammation of airways in chronic bronchitis. , 1985, British medical journal.

[28]  Movat Hz Demonstration of all connective tissue elements in a single section; pentachrome stains. , 1955 .

[29]  H. Movat,et al.  Demonstration of all connective tissue elements in a single section; pentachrome stains. , 1955, A.M.A. archives of pathology.