Lower airway colonization and inflammatory response in COPD: a focus on Haemophilus influenzae

Abstract

Bacterial infection of the lower respiratory tract in chronic obstructive pulmonary disease (COPD) patients is common both in stable patients and during acute exacerbations. The most frequent bacteria detected in COPD patients is Haemophilus influenzae, and it appears this organism is uniquely adapted to exploit immune deficiencies associated with COPD and to establish persistent infection in the lower respiratory tract. The presence of bacteria in the lower respiratory tract in stable COPD is termed colonization; however, there is increasing evidence that this is not an innocuous phenomenon but is associated with airway inflammation, increased symptoms, and increased risk for exacerbations. In this review, we discuss host immunity that offers protection against H. influenzae and how disturbance of these mechanisms, combined with pathogen mechanisms of immune evasion, promote persistence of H. influenzae in the lower airways in COPD. In addition, we examine the role of H. influenzae in COPD exacerbations, as well as interactions between H. influenzae and respiratory virus infections, and review the role of treatments and their effect on COPD outcomes. This review focuses predominantly on data derived from human studies but will refer to animal studies where they contribute to understanding the disease in humans.

Keywords: Haemophilus influenzae; chronic obstructive pulmonary disease; nontypeable Haemophilus influenzae; respiratory viruses; vaccination.

Figure 1

Interactions between chronic obstructive pulmonary disease (COPD), virus infection, and persistent infection with Haemophilus influenzae. Structural changes in the airways and impaired innate and acquired immunity in COPD are exploited by H. influenzae, leading to failure to eradicate the organism and persistent infection. Virus infections may also cause epithelial damage and immune suppression and may favor persistent infection. Persistent infection with H. influenzae enhances airway inflammation and may contribute to disease progression in COPD. Abbreviations: ↑, increased; ↓, decreased.