Relationship between airway inflammation and the frequency of exacerbations in patients with smoking related COPD

Abstract

Background-Patients with more frequent exacerbations of chronic obstructive pulmonary disease (COPD) may have increased bronchial inflammation. Airway inflammation was measured in patients who had been thoroughly investigated with full pulmonary function testing, thoracic HRCT scanning, and sputum microbiology to examine further the relationship between exacerbation frequency and bronchial inflammation. Conclusions-There are several clinical features that directly influence bronchial inflammation in COPD. When these were carefully controlled for, patients with more frequent reported exacerbations had lower sputum concentrations of SLPI. This important antiproteinase is also known to possess antibacterial and antiviral activity. Further studies are required into the nature of recurrent exacerbations and, in particular, the regulation and role of SLPI in aVected individuals. (Thorax 2001;56:36-41) Keywords: chronic obstructive pulmonary disease; inflammation; secretory leukoprotease inhibitor (SLPI) Chronic obstructive pulmonary disease (COPD) comprises a heterogeneous group of conditions, characterised by varying degrees of expiratory airflow limitation, related to combinations of abnormalities in the large and small airways and to alveolar destruction. The patients have a reduced state of health that is (loosely) related to the degree of physiological abnormality.

Oxidative stress and redox regulation of lung inflammation in COPD

“…Circulating neutrophils from cigarette smokers and patients with exacerbations of COPD release more O 2 N- [6]. Cigarette smoking is associated with increased content of myeloperoxidase (MPO) in neutrophils [7,8], which correlates with the degree of pulmonary dysfunction [7][8][9]. This suggests that neutrophil MPO-mediated oxidative stress plays a role in lung inflammation.…”

Outcomes for COPD pharmacological trials: from lung function to biomarkers

“…weeks or months), this variable does not appear to be reproducible due to the small number of episodes per yr; the probability of repeating an episode in weeks or months is small. However, in the long term, patients with frequent exacerbations in the past have a large probability of suffering frequent exacerbations in the future [194,199]. In COPD patients, there is also a short-term [36] and a long-term impact of exacerbations on HRQoL [178][179][180]200].…”

Chronic obstructive pulmonary disease: molecular and cellularmechanisms

“…Acute exacerbations may be prolonged and have a profound effect on the quality of life [246] and may accelerate the progression of COPD [247]. It was always assumed that the increased amount and purulence of sputum signified bacterial infection of the respiratory tract, but it is now evident that many exacerbations in COPD (as in asthma) are also due to upper respiratory tract viral infections (particularly rhinovirus) and to environmental factors, such as air pollution and temperature [248,249] There is an increase in neutrophils and concentrations of IL-6, IL-8, TNF-a and LTB 4 in sputum during an exacerbation [250,251] and patients who have frequent exacerbations have higher levels of IL-6 and lower concentrations of SLPI, even when COPD is stable [252,253]. There is also an increase in the activation of NF-kB in alveolar macrophages during exacerbations of COPD, providing a link between infections, oxidative stress and the enhanced expression of inflammatory genes [74].…”