Page 165 - ADULT-ONSET ASTHMA PREDICTORS OF CLINICAL COURSE AND SEVERITY

Part 1 of this thesis examines the diagnos c accuracy of several biomarkers to iden fy the presence of eosinophilic airway in amma on and serves as a method check for this speci c in ammatory asthma phenotype. In Chapter 3 the in uence of di erent adult-onset asthma phenotypes on biomarkers of sputum eosinophilia is addressed. Levels of eosinophils in blood and sputum, FeNO and total IgE from 336 adult pa ents, enrolled in 3 prospec ve observa onal clinical trials, were analyzed. In the total group the AUC was 0.83 (95%CI 0.78- 0.87) for blood eosinophils, 0.82 for FeNO (0.77-0.87) and 0.69 (0.63-0.75) for total IgE. Blood eosinophils and FeNO had comparable diagnos c accuracy (superior to total IgE) to iden fy sputum eosinophilia in adult asthma pa ents irrespec ve of asthma phenotype such as severe, non-atopic, obese and smoking-related asthma. In order to increase the clinical u lity of biomarkers, combined markers were tested and high and low cuto values were used. This method generates more diagnos c certainty for blood eosinophils and FeNO and might be useful to direct therapy adjustment.
Chapter 4 con nues on biomarkers of eosinophilic airway in amma on and examines the ques on: how accurate are surrogate markers in detec ng sputum eosinophilia in a general asthma popula on? A systema c review and meta-analysis to iden fy and pool all studies about biomarkers of airway eosinophilia in asthma pa ents have been performed. We included 24 studies in adults with asthma. Three markers had extensively been inves gated: Frac on of Exhaled Nitric Oxide (FeNO) (17 studies; 3,216 pa ents; summary area under the receiver operator curve (AUC) 0.75 (95%CI 0.72-0.78)); blood eosinophils (14 studies; 2,405 pa ents; AUC 0.78 (0.74-0.82)); total Immunoglobulin E (IgE) (7 studies; 942 pa ents; AUC 0.65 (0.61-0.69)). Assessment of eosinophilic airway in amma on is possible with these biomarkers; however, one has to bear in mind that their use as a single surrogate marker for airway eosinophilia in asthma c pa ents will lead to a substan al number of false posi ves and/or nega ves.
Chapter 5 contains a commentary on a study in which FENO and blood eosinophils were associated with allergic asthma, but only in non-smokers. Although these ndings do not necessarily raise ques ons about the clinical value of these biomarkers in smokers, they do show us that their poten al value is likely to be di erent in this large subgroup of asthma pa ents. In an era where phenotypoing and subphenotping pa ents has become increasingly mandatory in the clinical workup of asthma pa ents; smoking status seems to be an important determinant in this di eren a on.
Part 2 of this thesis addresses the clinical course of adult-onset asthma. Results presented in this part of the thesis are mainly based on data collected in the Adonis-study. In this prospec ve study two hundred adult pa ents with recently diagnosed (<1 year) asthma were included and followed for 5 years. Clinical, func onal and in ammatory parameters were assessed at baseline and at yearly visits.
In Chapter 6 the rst ques on: ‘which factors predict remission and persistence of adult-
SUMMARY AND GENERAL DISCUSSION
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