Page 172 - ADULT-ONSET ASTHMA PREDICTORS OF CLINICAL COURSE AND SEVERITY

ADULT-ONSET ASTHMA – PREDICTORS OF CLINICAL COURSE AND SEVERITY
asthma, more pack years were associated with more severe asthma.53 Others found that ac ve smoking predicted an accelerated decline in FEV1.49, 51 A recent longitudinal study in pa ents with adult-onset asthma found smoking as a predictor of uncontrolled asthma40 and accelerated decline in lungfunc on.54 Altogether, our study ts in with the increasing body of evidence poin ng at smoking as important nega ve determinant for asthma prognosis.
Finally, the associa on of frequent exacerba ons in never smokers with eosinophilia ts in with previous reports as would have been expected.21, 55 Also in childhood onset asthma eosinophilia has been shown to be predic ve of asthma exacerba ons. Due to the considerable number of (ex)smokers in our study, we were able to analyze this important subgroup of asthma pa ents separately. Here we found an associa on between frequent exacerba ons and neutrophilia. For asthma pa ents this was a novel nding, although it resembles previous ndings in COPD pa ents. Two studies found increased levels of blood neutrophils in COPD pa ents with exacerba ons.56, 57
INTERPRETATION OF THE RESULTS
The ndings in our study might give clues about the underlying mechanisms determining the clinical course of asthma. Nasal polyps might be a symptom of generalised airways disease, which re ects the severity and extensiveness of the disease. Probably there are common causal mechanisms involved in the development of both nasal polyps and asthma. S muli like viruses, bacteria, allergens and toxins lead to ac va on of type 2 in amma on via T helper 2 (Th2) cells and group 2 innate lymphoid cells (ILC2). Via cytokine release this leads to recruitment and/or ac va on of mast cells, eosinophils, basophils, goblet cells, M2 macrophages, B cells and ssue responses.58 In ux and ac va on of in ammatory cells will eventually lead to nasal polyps and, when lower airways are involved, also to asthma. The rela on with asthma persistence and more severe BHR might also be a re ec on of this ac ve in ammatory process leading to airway smooth muscle ac va on and thereby a higher degree of airway hyperreac vity.
From the above men oned e ector cells, eosinophilic in amma on plays a very important role in adult-onset asthma and is not speci cally related to allergic in amma on.59 We have shown that blood eosinophils relate to frequent exacerba ons in never smokers with adult- onset asthma, FeNO did not. This might be related to di erent mechanism leading to an increase in these biomarkers. FeNO increases typically a er allergen exposure which leads to produc on of IL4 and IL13, upregulates iNOS in the airway epithelium followed by produc on of NO.60 Whereas IL5 produc on by ILC2s in response to non-allergic s muli speci cally leads to eosinophilia, and is not necessarily related to allergen exposure.59 This ts in with the adult- onset eosinophilic non-allergic asthma phenotype.
Smoking is an important determinant for the severity of asthma. The e ects might be related to several mechanisms induced by cigare e smoke including altered airway in amma on, airway remodelling and insensi vity to cor costeroids. Smoking is known to cause non
170