Targeting airway inflammation in cystic fibrosis

ABSTRACT

Introduction: The major cause of morbidity and mortality in patients with cystic fibrosis (CF) is lung disease. Inflammation in the CF airways occurs from a young age and contributes significantly to disease progression and shortened life expectancy.

Areas covered: In this review, we discuss the key immune cells involved in airway inflammation in CF, the contribution of the intrinsic genetic defect to the CF inflammatory phenotype, and anti-inflammatory strategies designed to overcome what is a critical factor in the pathogenesis of CF lung disease. Review of the literature was carried out using the MEDLINE (from 1975 to 2018), Google Scholar and The Cochrane Library databases.

Expert opinion: Therapeutic interventions specifically targeting the defective CF transmembrane conductance regulator (CFTR) protein have changed the clinical landscape and significantly improved the outlook for CF. As survival estimates for people with CF increase, long-term management has become an important focus, with an increased need for therapies targeted at specific elements of inflammation, to complement CFTR modulator therapies.

KEYWORDS:

• Cystic fibrosis
• inflammation
• therapeutic targets

Article highlights

• Cystic fibrosis (CF) lung disease is characterized by extensive, chronic neutrophilic inflammation of the airways, with other immune cells such as macrophages and T-lymphocytes also playing an important role.

• Airways inflammation in CF occurs from an early age, before recognized clinical measures become markedly abnormal, and contributes significantly to disease progression and shortened life expectancy.

• As people with CF (PWCF) live longer, an increased need for anti-inflammatory therapies has arisen, to complement cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies.

• In addition to broad-spectrum anti-inflammatory strategies such as ibuprofen and corticosteroids, other more specific therapies have targeted protease activity, regulation of neutrophil influx, oxidants, lipid abnormalities and other drivers of inflammation.

• This review elaborates on the rationale behind these approaches and the existing evidence base for their use in CF.

Declaration of interest

NG McElvaney has previously been an investigator in trials for CSL Behring, Galapagos and Vertex. He has previously sat on advisory boards for CSL Behring, Grifols, Chiesi and Shire. These companies had no role in the funding of this manuscript. The authors have no other 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 apart from those disclosed.

Reviewer disclosures

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

Additional information

Funding

This paper was funded by the Royal College of Surgeons in Ireland StAR-MD Programme.