Relationship between bacterial colonisation and the frequency, character, and severity of COPD exacerbations

Abstract

Background: Patients with chronic obstructive pulmonary disease (COPD) are prone to frequent exacerbations which are a significant cause of morbidity and mortality. Stable COPD patients often have lower airway bacterial colonisation which may be an important stimulus to airway inflammation and thereby modulate exacerbation frequency. Methods: Twenty nine patients with COPD (21 men, 16 current smokers) of mean (SD) age 65.9 (7.84) years, forced expiratory volume in 1 second (FEV 1 ) 1.06 (0.41) l, FEV 1 % predicted 38.7 (15.2)%, FEV 1 /FVC 43.7 (14.1)%, inhaled steroid dosage 1.20 (0.66) mg/day completed daily diary cards for symptoms and peak flow over 18 months. Exacerbation frequency rates were determined from diary card data. Induced sputum was obtained from patients in the stable state, quantitative bacterial culture was performed, and cytokine levels were measured. Results: Fifteen of the 29 patients (51.7%) were colonised by a possible pathogen: Haemophilus influenzae (53.3%), Streptococcus pneumoniae (33.3%), Haemophilus parainfluenzae (20%), Branhamella catarrhalis (20%), Pseudomonas aeruginosa (20%). The presence of lower airway bacterial colonisation in the stable state was related to exacerbation frequency (p=0.023). Patients colonised by H influenzae in the stable state reported more symptoms and increased sputum purulence at exacerbation than those not colonised. The median (IQR) symptom count at exacerbation in those colonised by H influenzae was 2.00 (2.00-2.65) compared with 2.00 (1.00-2.00) in those not colonised (p=0.03). The occurrence of increased sputum purulence at exacerbation per patient was 0.92 (0.56-1.00) in those colonised with H influenzae and 0.33 (0.00-0.60) in those not colonised (p=0.02). Sputum interleukin (IL)-8 levels correlated with the total bacterial count (rho=0.459, p=0.02). Conclusion: Lower airway bacterial colonisation in the stable state modulates the character and frequency of COPD exacerbations.

Colonization and Bronchiectasis in Patients with Advanced Chronic Obstructive Pulmonary Disease

“…These results broadly concur with Patel et al who reported a positive correlation between lower airway bacterial colonization and exacerbation frequency [22]. In contrast to previous reports that associated tobacco exposition with rates of bacterial colonization [14,22], we observed no difference. Given the requirement for tobacco abstinence prior to lung transplantation evaluation, rates of active smoking in our cohort were extremely low, with elevated Hb-CO being identified in only 4% of patients.…”

Role of T-lymphocytes and pro-inflammatory mediators in the pathogenesis of chronic obstructive pulmonary disease

“…Bacterial colonization of the airways in COPD patients with even mild airfl ow obstruction is frequent (Soler et al 1999;Sethi et al 2006), and hence these particular microbes seem to be likely suspects as the source of disease-causing exogenous antigens. These bacterial colonizations are associated with recurrent COPD exacerbations, more rapid declines in lung function, and are correlated with a number of infl ammatory markers in sputum and in BAL Patel et al 2002;Wilkinson et al 2003;Banerjee et al 2004).…”

“…IL-8 levels are increased in sputum of patients with COPD (Keatings et al 1996;Yamamoto et al 1997), and are further augmented during disease exacerbations, presumably in association with neutrophilic infl ammation triggered by bacteria (Crooks et al 2000;Aaron et al 2001;Gompertz et al 2001). Airway microbes induce IL-8 secretion by epithelial cells, and levels of this cytokine have been shown to correlate with airway bacterial load Patel et al 2002). Interestingly, blocking antibodies to IL-8 only led to a modest reduction in the neutrophilic infl ammation (Beeh et al 2003).…”

Differential regulation ofMoraxella catarrhalis-induced interleukin-8 response by protein kinase C isoforms

“…Among them, interleukin (IL)-8, a member of the CXC chemokine family, plays a pivotal role in regulating neutrophil and monocyte chemotaxis toward sites of infection, and in inducing airway inflammation [9,10]. The presence of microorganisms such as M. catarrhalis in the lower respiratory tract of COPD patients has been found to increase IL-8 release in bronchoalveolar lavage of COPD patients, which is associated with disease progression [11][12][13]. Transcriptional regulation of IL-8 is controlled by a tight regulatory signalling network, most importantly involving the nuclear factor (NF)-kB.…”