Page 132 - ADULT-ONSET ASTHMA PREDICTORS OF CLINICAL COURSE AND SEVERITY

ADULT-ONSET ASTHMA – PREDICTORS OF CLINICAL COURSE AND SEVERITY
up visit. Therefore, we were not able to determine whether asthma in smokers might have evolved phenotypically into COPD. However, there was a trend for a lower postbronchodilator FEV1/FVC ra o in pa ents with increased asthma severity as compared to those whose asthma had improved, sugges ng the development of persistent air ow limita on.
We chose to use the GINA score for classifying asthma severity because it is a composite score of asthma control, lung func on and treatment.9 Asthma severity is thus assessed in a broad and realis c perspec ve, which is important especially when evalua ng changes in severity over me. In our opinion, missing data on ACQ-score or FEV1 in a small propor on of our pa ents was not relevant, because an accurate es ma on of the severity score could s ll be made (see Fig. E1).
Our results could have been biased by the rather large propor on of pa ents who were lost to follow-up. Pa ents who were lost to follow-up were more o en non-smoking women using lower doses of inhaled cor costeroids than the par cipants, sugges ng that they had milder asthma and did not require regular follow-up. One might argue that the higher number of smokers amongst the par cipants as compared to those who were lost to follow-up might have in uenced our results. However, a small enrichment of the popula on with (ex-)smokers is not expected to a ect the results of a logis c regression analysis.
The most likely explana on for the e ect of (ex-)smoking on asthma deteriora on is persistent smoking-induced in ammatory pa ern, which is glucocor coid insensi ve. Ac ve smoking changes the type of airway in amma on towards more mast cells and neutrophils and less eosinophils.31;32 Ex-smoking asthma cs are more frequently known to have neutrophilic airway in amma on,32 which is associated with glucocor coid insensi vity. Smoking is also known to cause airway remodelling, with an increased epithelial wall thickness and more goblet cells in bronchi, leading to more symptoms of dyspnea and sputum produc on. A longitudinal study with a follow-up period of 23 years showed that the protec ve e ect of inhaled cor costeroids on lung func on decline was absent in pa ents who had smoked > 5 pack years.33 However, reduced bene cial e ects of inhaled glucocor coids caused by smoking were found in some, but not in all studies.34;35 The results of our study support the hypothesis that smoking, even for a short period of me, has persistent e ects on cor costeroid sensi vity, leading to rapid increase in asthma severity despite eleva on of inhaled steroid doses shortly a er asthma diagnosis.
The results from this study have a number of clinical implica ons. Clinicians should be alert on an increase in asthma severity in pa ents with new-onset adult asthma who have a history of smoking. These pa ents are prone to a more rapid increase in asthma severity, and early therapeu c interven on is therefore warranted. Since cor costeroids are less e ec ve in smokers than in non-smokers,34 novel targeted therapeu c op ons might be more suitable for these pa ents.
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