Pseudomonas aeruginosa in bronchiectasis: infection, inflammation, and therapies

ABSTRACT

Introduction: Bronchiectasis is a chronic endobronchial suppurative disease characterized by irreversibly dilated bronchi damaged by repeated polymicrobial infections and predominantly, neutrophilic airway inflammation. Some consider bronchiectasis a syndromic consequence of several different causes whilst others view it as an individual disease entity. In most patients, identifying an underlying cause remains challenging. The acquisition and colonization of affected airways by Pseudomonas aeruginosa represent a critical and adverse clinical consequence for its progression and management.

Areas covered: In this review, we outline clinical and pre-clinical peer-reviewed research published in the last 5 years, focusing on the pathogenesis of bronchiectasis and the role of P. aeruginosa and its virulence in shaping host inflammatory and immune responses in the airway. We further detail its role in airway infection, the lung microbiome, and address therapeutic options in bronchiectasis.

Expert opinion: P. aeruginosa represents a key pulmonary pathogen in bronchiectasis that causes acute and/or chronic airway infection. Eradication can prevent adverse clinical consequence and/or disease progression. Novel therapeutic strategies are emerging and include combination-based approaches. Addressing airway infection caused by P. aeruginosa in bronchiectasis is necessary to prevent airway damage, loss of lung function and exacerbations, all of which contribute to adverse clinical outcome.

KEYWORDS:

• Bronchiectasis
• Pseudomonas aeruginosa
• pathogenesis
• exacerbations
• therapy

Article highlights

• Pseudomonas aeruginosa is an important contributor in the pathogenesis of bronchiectasis. It secretes a range of virulence factors that promote cellular adhesion and tissue invasion, inhibits muco-ciliary function, dysregulates host immunity which collectively result in airway inflammation and tissue damage.

• Cycles of infection and inflammation in bronchiectasis create a favorable environment for pathogens, such as P. aeruginosa, to establish and colonize the airway. Although inherent heterogeneity exists in non-cystic fibrosis bronchiectasis, levels of airway inflammation and bacterial colonization do correlate with disease severity and exacerbation frequency.

• P. aeruginosa remains one of the predominant bacterial species present in the lower respiratory tract of patients with bronchiectasis. Shifts to bacterial composition, particularly when P. aeruginosa outcompetes other species, associates with an increased frequency of exacerbations, greater disease severity including hospitalizations and marked declines to lung function. Depending on circumstances, P. aeruginosa in itself can be a cause or a consequence of bronchiectasis and therefore exploration of therapeutics to prevent exacerbations, reduce disease progression and improve patient care is warranted.

• The use of antimicrobials to target P. aeruginosa remains an important area of study. Macrolides exhibit anti-inflammatory and anti-infective properties and have shown benefit, particularly when used long term. However, optimal treatment, including dosage, frequency, and duration, remains unclear and a balance between clinical benefit and the prevention of microbial resistance must be considered.

• Despite significant advances in our understanding of bronchiectasis pathophysiology, many remains to be understood in the context of P. aeruginosa infection. Considering the significant clinical heterogeneity that exists between patients with bronchiectasis, patient stratification according to microbial and immune parameters including P. aeruginosa may be a promising avenue for targeted and improved patient care.

Declaration of interest

The author(s) have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.