Bacterial–viral load and the immune response in stable and exacerbated COPD: significance and therapeutic prospects

D’Anna, Silvestro Ennio; Balbi, Bruno; Cappello, Francesco; Carone, Mauro; Di Stefano, Antonino

Microbiome and immune response in COPD is correlated to airway inflammation in patients with stable chronic bronchitis. 17 Garcha et al 18 studied sputum samples from 134 patients by qPCR and observed that in stable COPD, a higher bacterial load was correlated to more severe bronchial obstruction, higher dosage of inhaled corticosteroids, and a higher C-reactive protein (CRP) level. More recently, Barker et al 19 studied sputum samples from 120 patients with stable COPD and paired sputum in 55 subjects with stable and exacerbated disease. Using qPCR, they observed that the majority of patients in a stable state (76%) had pathogenic bacteria in their airways. The detection of bacteria by means of nonculture-based techniques such as qPCR was also associated with increased sputum interleukin (IL)-1β, IL-10, and tumor necrosis factor α, and decreased Chemokine (C-C Motif) Ligand 13 (CCL13). In a stable state, the strongest relationship between bacterial load, inflammation, and symptoms was observed with H. influenzae, whether in codetection with other bacteria or as sole pathogen. Singh et al 20 analyzed the sputum of 99 stable COPD patients by qPCR and observed a direct correlation between the load of H. influenzae, S. pneumoniae, and M. catarrhalis and airway inflammation and plasmatic fibrinogen. Erb-Downward et al 21 analyzed bronchoalveolar lavage (BAL) fluid of three never smokers, seven healthy smokers, four COPD patients, and eight samples obtained from six patients undergoing lung transplantation for COPD. A significant bacterial load was found in all subjects without significant differences between groups. In some smokers with normal lung function, the authors found a lower diversity of lung microbiota and speculated that this relative reduction in the diversity could be persistent and could be either an "effect" of the lung inflammation or, in part, a "cause" of disease onset and progression. 21 The molecular aspects of these dynamic modifications in the bacterial load and bacterial types in relation to the patient's immune response need to be studied. It has been hypothesized that the appearance of new strains of foreign microbes initiates a cycle of infection, inflammatory response, and dysfunctional remodeling driving the progression of COPD. 17, 22 Sze et al 23 analyzed samples from surgical lung resections and lung transplant donors of smokers (eight samples), nonsmokers (eight samples), COPD patients (eight samples), and cystic fibrosis patients (eight samples). They showed differences in the bacterial community of the COPD lung tissue compared with other groups. Actinobacteria were more abundant in the smoker group, while Lactobacillus were consistently present in the COPD Global Initiative for Chronic Obstructive Lung Disease (GOLD) 4 group. In the cystic fibrosis and COPD groups, the Burkholderia genus represented more than 5% of the bacterial community. The increased presence of Lactobacillus in the lung could be related to an inflammatory state associated to the formation of tertiary lymphoid follicles developing near the small airways. 23 Lactobacillus could either be the target of the inflammation or, alternatively, it could act as an immune modulator and aid the inflammatory response. In their study, the authors showed that in the very severe COPD group, there was a shift in the relative abundance of a few bacterial populations without any one becoming dominant.