A clinico-pathological study of COPD

Abstract

Smokers with and without COPD and non-smoking controls underwent detailed clinical evaluation followed by quantitative high-resolution computed tomography (HRCT), sputum induction and endobronchial biopsy analysis.

The relationship between clinical and HRCT indicators of COPD severity was examined.  Expiratory HRCT measurements and the expiratory/inspiratory mean lung density ratio (indicators of peripheral airway dysfunction) correlated more closely with airflow obstruction than did inspiratory HRCT measurements (which reflect emphysema severity).

Proximal airway inflammation was related, for the first time, to small airways dysfunction and emphysema (as determined by HRCT).  Sputum neutrophils correlated with peripheral airways dysfunction but not with emphysema severity, while submucosal CD8+ T cell counts correlated weakly with airflow obstruction and HRCT measurements of emphysema.

Neutrophils and the Epidermal Growth Factor Receptor (EGFR) are implicated in the generation of epithelial goblet cell hyperplasia.  Epithelial ErbB receptor and mucin expression were characterised, for the first time, in smokers.  EGFR, ErbB3 and MUC5AC expression were elevated in smokers.  ErbB3 expression correlated with MUC5AC expression and was expressed by mucin producing cells.  No correlation was observed between mucin or ErbB receptor expression and either COPD severity or neutrophil counts.

The neutrophil chemokines Interleukin 8 (IL-8) and growth related oncogene - α (GRO-α) are possible contributors to neutrophilic inflammation in COPD.  Both were measured in sputum and epithelium.  Expression of both was increased in sputum, but not epithelium, of smokers with COPD.  However, sputum IL-8 was negatively associated with current smoking habit while neither chemokine correlated with either disease severity or neutrophilic inflammation.

The results suggest that peripheral airway dysfunction is a key determinant of COPD severity and that sputum neutrophilia is an indicator of peripheral airway dysfunction severity.

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