Neutrophilic asthma: misconception or misnomer?

Neutrophils are abundant in the circulation. These cells are recruited into the airways in a number of circumstances—eg, following exposure to pollutants and pathogens or in response to a diet rich in fat and carbohydrate. Upon activation in the airways, neutrophils can release their granules, DNA, and proteins, and could contribute to airway damage. Several signalling mechanisms and pathways of egress of neutrophils from the bone marrow, chemotaxis of neutrophils into the airway, and persistence of neutrophils in the airways caused by delayed resolution of inflammatory signals have been elucidated. These signalling mechanisms include, but are not limited to, the following: balanced activity between CXCR2 and CXCR4 signalling; cytokines such as IL-1β, IL-6, IL-8, TNF, GROα, IL-17, IL-23, IFN-γ, phosphoinositide 3-kinase, NLRP3 inflammasome, galectin-10, and dipeptidase-1, and lipid mediators such as leukotriene B4, lipoxins, resolvins; and an intricate network of microRNAs. 1 Ray A Kolls JK Neutrophilic inflammation in asthma and association with disease severity. Trends Immunol. 2017; 38: 942-954 Summary Full Text Full Text PDF PubMed Scopus (159) Google Scholar Neutrophils have been found in sputum, bronchial wash, bronchoalveolar lavage, tracheal aspirates, and bronchial biopsies, in many cross-sectional studies, with their numbers increasing with disease severity in adults and children with asthma. 2 Nair P Aziz-Ur-Rehman A Radford K Therapeutic implications of ‘neutrophilic asthma’. Curr Opin Pulm Med. 2015; 21: 33-38 Crossref PubMed Scopus (36) Google Scholar This increase in neutrophil number is, not surprisingly, associated with the expression of factors that promote neutrophilia and might not necessarily be stable over time. 3 Kermani NZ Pavlidis S Xie J et al. Instability of sputum molecular phenotypes in U-BIOPRED severe asthma. Eur Respir J. 2020; (published online Oct 2.)https://doi.org/10.1183/13993003.01836-2020 PubMed Google Scholar The association between asthma severity and neutrophil number has led to the use of the term neutrophilic asthma, 4 Wood LG Baines KJ Fu J Scott HA Gibson PG The neutrophilic inflammatory phenotype is associated with systemic inflammation in asthma. Chest. 2012; 142: 86-93 Summary Full Text Full Text PDF PubMed Scopus (189) Google Scholar which implies the existence of a specific asthma endotype in which neutrophils are the major cell type mediating pathobiology, severity, and symptoms. However, it is unresolved whether this is indeed the case.