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

Chronic obstructive pulmonary disease (COPD) is characterized by a persistent airflow limitation usually associated with an increased inflammatory response. 1 Bronchial biopsies of stable mild COPD patients show increased levels of inflammatory cells compared with healthy nonsmokers; among these cells, CD8 + T-lymphocytes, neutrophils, and macrophages are prevalent. 1, 2 In severe COPD, while there is a decrease in the total number of inflammatory cells, a prevalence of inflammatory cells with phagocytic and proteolytic activity, such as neutrophils and macrophages, is reported. 2 Acute exacerbations of COPD can cause a worsening of lung function that lasts many weeks, accelerating the rate of lung function decline. 1 Viral and bacterial infections of the respiratory system are a major cause of COPD exacerbations. Microbiological examination of sputum from COPD patients hospitalized during an exacerbation shows that infections are mostly associated with bacterial pathogens of the sputum, followed by combined bacteria and viruses or sputum viruses. 3 Another study, 4 followed COPD patients for 1 year, observed a high rate of exacerbations in one subgroup -37% of these were caused by bacteria, 10% by viruses, 12% by bacteria and viruses, while 14% were of undefined origin. 4 Many investigators have observed a change of the inflammatory response in COPD patients during acute exacerbations, showing a general increase in the inflammatory state. 2 These exacerbations are associated with an increase in neutrophils, T-lymphocytes, and, in some cases, eosinophils. [4] [5] [6] Viruses and bacteria may cause acute exacerbations of COPD, or alternatively, they may amplify chronic inflammation in stable COPD. 7 The aforementioned data, however, come from separate experimental sets using different methodological approaches, rendering difficult a direct comparison between bacterial-viral loads in the lungs of COPD patients and the related immune host responses. To date, few data are available on the dynamic mechanisms of bacteria and viruses colonizing the lungs, or the precise relationship between these events and disease progression during stable and exacerbated COPD. This review focuses on the present knowledge regarding the microbiome load (either bacteria or viruses) in stable and exacerbated COPD. We will not deal in depth here with the immune response related to bacterial-viral infections, since other reviews have already been published on this topic and also because there are few in vivo data available. We will focus instead on the dynamic events involved in COPD progression and touch on future prospects for therapeutic strategies.