Relationship between peripheral airway dysfunction, airway obstruction, and neutrophilic inflammation in COPD

Background: Considerable research has been conducted into the nature of airway inflammation in chronic obstructive pulmonary disease ( COPD) but the relationship between proximal airways inflammation and both dynamic collapse of the peripheral airways and HRCT determined emphysema severity remains unknown. A number of research tools have been combined to study smokers with a range of COPD severities classified according to the GOLD criteria. Methods: Sixty five subjects ( 11 healthy smokers, 44 smokers with stage 0 - IV COPD, and 10 healthy nonsmokers) were assessed using lung function testing and HRCT scanning to quantify emphysema and peripheral airway dysfunction and sputum induction to measure airway inflammation. Results: Expiratory HRCT measurements and the expiratory/inspiratory mean lung density ratio ( both indicators of peripheral airway dysfunction) correlated more closely in smokers with the severity of airflow obstruction ( r = -0.64, p< 0.001) than did inspiratory HRCT measurements ( which reflect emphysema severity; r = -0.45, p< 0.01). Raised sputum neutrophil counts also correlated strongly in smokers with HRCT indicators of peripheral airway dysfunction ( r = 0.55, p< 0.001) but did not correlate with HRCT indicators of the severity of emphysema. Conclusions: This study suggests that peripheral airway dysfunction, assessed by expiratory HRCT measurements, is a determinant of COPD severity. Airway neutrophilia, a central feature of COPD, is closely associated with the severity of peripheral airway dysfunction in COPD but is not related to the overall severity of emphysema as measured by HRCT.