Paucigranulocytic asthma: The uncoupling of airway obstruction from inflammation

Publication date: Available online 19 June 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Omar Tliba, Reynold A. Panettieri
Among patients with asthma, heterogeneity exists regarding the pattern of airway inflammation and response to treatment, prompting the necessity of recognizing specific phenotypes. Based on the analysis of inflammatory cell count in induced sputum, patients with asthma can be classified in four unique phenotypes; eosinophilic, neutrophilic, mixed granulocytic, and paucigranulocytic asthma (PGA). PGA is an asthma phenotype with no evidence of elevated numbers of eosinophils or neutrophils in sputum or blood, and in which anti-inflammatory therapies are ineffective in controlling symptoms. While under-investigated, PGA is the most common asthma phenotype in patients with stable asthma. However, PGA is sometimes underestimated due to the exclusive reliance on induced sputum cell count which is variable among cohorts of studies prompting the necessity of developing improved biomarkers. Importantly, investigators have reported that inhaled corticosteroids had limited effect on airway inflammatory markers in patients with PGA defining, therefore, PGA as a potentially "steroid-insensitive" phenotype that requires exploration of alternative therapies. PGA manifests as an uncoupling of airway obstruction from airway inflammation that can be driven by structural changes within the airways such as airway smooth muscle (ASM) tissue hypertrophy. Animal models provide evidence that processes evoking airway hyperresponsiveness and ASM thickening occur independent from inflammation and may be a consequence of a loss of negative homeostatic processes. Collectively, further understanding of PGA with focus on the characterization, prevalence, clinical significance and pathobiology derived from animal studies will likely provide precision therapies that will improve PGA clinical outcomes.



https://ift.tt/2tmAidT