Page 114 - ADULT-ONSET ASTHMA PREDICTORS OF CLINICAL COURSE AND SEVERITY

ADULT-ONSET ASTHMA – PREDICTORS OF CLINICAL COURSE AND SEVERITY
allergic rhini s have been shown to predict asthma onset,29, 30 and chronic rhinosinusi s is an important comorbid condi on in pa ents with asthma.31 More importantly, chronic rhinosinusi s with nasal polyposis is associated with greater asthma severity and frequent exacerba ons.32 Nasal polyposis as a predictor of chronicity and persistence of new onset asthma has not been reported before, although it is conceivable that asthma will persist as long as nasal polyps persist, since both are likely manifesta ons of the same underlying pathophysiological process.33
Our study shows that apart from comorbid nasal polyps, the persistence of asthma is associated with the severity of the disease itself as reflected by increased bronchial responsiveness, although this associa on was six mes weaker than for nasal polyps. Previous studies already reported an important role for bronchial hyperresponsiveness in the prognosis of asthma pa ents, in par cular for predic ng accelerated decline in FEV1.34 Our ndings also t in with data obtained in childhood asthma, showing that asthma persistence is strongly linked to greater frequency and severity of asthma symptoms, and more severe airway hyperresponsiveness.35 However, unlike in children, atopic sensi za on was not a predictor of persistence in our study of adults with new onset asthma.36
The associa on of nasal polyposis with asthma persistence in our study was strong, yet, only a quarter of the pa ents with adult-onset asthma showed this condi on. For pa ents without nasal polyposis, predictors of asthma persistence were less obvious. In a post-hoc evalua on of these pa ents, they appeared to be more frequently female and more o en obese than pa ents with nasal polyps and to have poor asthma control (data shown in Table 3). In addi on, these pa ents showed an increase in neutrophils over the years. This set of clinical characteris cs ts in with a speci c phenotype of adult-onset asthma, the so-called “obese female asthma phenotype” which has been iden ed in several large cluster analysis studies.3, 37, 38 and have been shown to have neutrophilic in amma on.39, 40 Apparently, pa ents with obesity associated asthma are not likely to achieve asthma remission, despite posi ve e ects of weight loss in other studies.41
An alterna ve explana on might be the presence of chronic rhinosinusi s without nasal polyposis, which was observed in almost half of pa ents, and could have led to airway neutrophilia. This increase in non-type 2 in amma on suggests ac va on of Th17 and Th1 pathways, caused for instance by recurrent respiratory infec ons or exposure to environmental pollutants and thereby leading to persistent asthma.42
What could be mechanisms leading to persistent asthma? Given the strong associa on between asthma persistence and nasal polyposis, it is likely that common causal mechanisms play a role in the development and persistence of both diseases. These include immune responses against fungi, bacteria, or bacterial enterotoxins leading to type 2 in amma on in both upper and lower airways.43 Another factor that might induce and maintain both diseases
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