Page 154 - ADULT-ONSET ASTHMA PREDICTORS OF CLINICAL COURSE AND SEVERITY

ADULT-ONSET ASTHMA – PREDICTORS OF CLINICAL COURSE AND SEVERITY
DISCUSSION
This study shows that never smoking and (ex)smoking pa ents with severe asthma have di erent predictors for frequent exacerba ons. In never smokers higher blood eosinophils are associated with frequent exacerba ons, as would be expected. However, in (ex)smokers higher blood neutrophils and higher ICS dose, are associated with frequent exacerba ons. These results suggest that di erent types of systemic background in amma on play a role in the ae ology of frequent exacerba ons in (ex)smoking and never smoking adult asthma pa ents.
In our study we compared predictors of frequent exacerba ons between never smokers and (ex)smokers with severe asthma. Previous studies inves gated risk factors of frequent exacerba ons in asthma in general, without making a dis nc on between (ex)smokers and never smokers. The associa on between blood or sputum eosinophilia and exacerba ons has been reported in several reports,4,24 which is in line with our results in never smokers. Other predictors including recent exacerba ons,25 disease ac vity score,26 co-morbidi es14 and smoking15,27 were either not addressed or not con rmed in our study. Thus, in never smokers blood eosinophil counts are clearly associated with frequent exacerba ons.
Our results show that (ex)smokers have di erent risk factors of frequent exacerba ons than never smokers. Although all our pa ents had a con rmed diagnosis of asthma, were measured in a stable phase of their disease, and had a rela vely limited smoking history, the results show remarkable resemblance to ndings in pa ents with COPD. One study in COPD pa ents with frequent exacerba ons found an increased white blood cell count and neutrophil count to be associated with exacerba ons.28 Another COPD study found increased levels of blood and sputum neutrophils in pa ents with bacterial exacerba ons.29 The novel nding of our study is the dis nct in ammatory pa ern associated with frequent exacerba ons in (ex)smoking asthma pa ents, which suggests a dis nct in ammatory phenotype in these pa ents.
Several mechanisms could explain our ndings. Di erent in ammatory pro les in smokers and exsmokers with severe asthma have been observed previously.30 Compared to their never smoking counterparts (ex)smoking asthma pa ents have less eosinophils and more neutrophils in sputum, they have lower levels of FeNO, and are less o en sensi zed to common allergens.30 How smoking in uences airway in amma on and induces subsequent exacerba ons is not fully elucidated and several mechanisms could be involved. One possible pathway could be mobiliza on and ac va on of neutrophils via innate immune responses mediated by macrophages and Th17 cells induced by cigare e smoke.9 Altered immune responses caused by smoking31 make smokers more suscep ble to infec ons resul ng in exacerba ons.32 In addi on, changes in airway microbiome and bacterial coloniza on leading to a dominance of Haemophilus sp., Streptococcus sp. and M. catarrhalis are also associated with neutrophilic
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