Page 155 - ADULT-ONSET ASTHMA PREDICTORS OF CLINICAL COURSE AND SEVERITY

PREDICTORS OF FREQUENT EXACERBATIONS IN (EX)SMOKING AND NEVER SMOKING ADULTS WITH SEVERE ASTHMA
airway in amma on in severe asthma pa ents.33 Furthermore, higher levels of oxida ve stress in response to smoking par ally cause the cor costeroid resistance o en found in smokers with asthma and hence increase their suscep bility to exacerba ons.34 Taken together, an altered airway immune response and increased levels of oxida ve stress by smoking, resul ng in neutrophilic airway in amma on with more infec ons and reduced response to asthma therapy, might all contribute to an increased exacerba on risk.
Major strength of this study is the large cohort of extensively characterized adult asthma pa ents. In contrast to many other asthma-studies, we also included (ex)smokers which enabled us to study this important group of asthma pa ents as well. We acknowledge there are several limita ons in our study. Firstly, the cross-sec onal analysis of our data precludes assessing the temporal rela onship between exacerba ons and pa ents’ characteris cs. Therefore, our results have to be interpreted cau ously and ideally should be con rmed in prospec ve studies with careful documenta on of exacerba ons. Secondly, the use of oral cor costeroids by a large propor on of our pa ents may have introduced a bias, since oral cor costeroids are known to increase neutrophil numbers in peripheral blood. However, even a er correc on for oral cor costeroid use, blood neutrophil count was an independent predictor of frequent exacerba ons in the (ex)smoker group, which strengthens our ndings.
Our results have clinical implica ons. In order to improve asthma outcomes, clinicians may have to approach (ex)smokers and never smokers with asthma di erently, based on their speci c in ammatory cell pa ern in peripheral blood. Non-smoking pa ents with blood eosinophilia should have their steroid treatment adjusted according to eosinophil counts in order to reduce exacerba on frequency, as shown previously.5 In pa ents with persistent blood or sputum eosinophilia despite high dose inhaled cor costeroids, novel targeted therapies directed for example against interleukin (IL)-5 might be appropriate.8 For (ex)smokers with neutrophilic or non-eosinophilic asthma the treatment op ons are less obvious. Several compounds directed against neutrophils or neutrophil associated pathways have been studied in pa ents with neutrophilic asthma.35 For the majority of these compounds the bene cial e ects on asthma outcomes or airway in amma on are limited. Some studies have shown that smokers with asthma might bene t from small-size-par cle inhaled cor costeroids36 or low- dose azithromycin as add-on treatment to decrease the number of asthma exacerba ons.37 Yet, the exact pathophysiological role of neutrophils in (ex)smokers with severe asthma and the op mal treatment strategy remains to be elucidated.
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