Page 167 - ADULT-ONSET ASTHMA PREDICTORS OF CLINICAL COURSE AND SEVERITY

GENERAL DISCUSSION
PART 1 MARKERS OF DISEASE ACTIVITY; MEASURING AIRWAY INFLAMMATION
BIOMARKERS OF AIRWAY INFLAMMATION IN ASTHMA PATIENTS; A CRITICAL EVALUATION
Biomarkers are ge ng increasingly important in medicine, also in the eld of asthma.11 Eosinophilia in sputum has been regarded as a hallmark of asthma since many years.12 However, the assessment of this important asthma feature is me consuming and laborious. Many studies in pa ents with mainly childhood onset asthma tried to nd more easily accessible biomarkers for the presence of airway eosinophilia. Our meta-analysis in Chapter 3 pooled all these studies13 and shows that using a single biomarker to detect airway eosinophilia in asthma pa ents has moderate diagnos c accuracies. The biomarkers analyzed (blood eosinophils, FeNO and total IgE) all have summary es mates of AUC’s, sensi vi es and speci ci es that are far from perfect. As a result, when the reported cuto points are used in clinical prac ce will lead to many false posi ve and false nega ve outcomes. Two other recent reports 14, 15 drew the same conclusion that FeNO and blood eosinophils lack su cient sensi vity or speci city to be useful as markers of sputum eosinophilia. In order to increase the clinical usefulness of these biomarkers, we conducted a study where we reported biomarker thresholds at either high sensi vity or high speci city and combined markers in a predic on model (Chapter 4).16 These high or low cuto levels of the markers are more useful for physicians to respec vely con rm or exclude airway eosinophilia with high certainty. However, one should bear in mind that in up to half of the pa ents with intermediate biomarker levels the diagnos c uncertainty remains; these pa ents would s ll need to undergo sputum induc on to con rm or exclude sputum eosinophilia.
A general conclusion about part 1 of this thesis will be that biomarkers of airway eosinophilia in adult-onset asthma should be used with cau on. Several cri cal comments can be made when inves ga ng and using biomarkers of airway in amma on in asthma. This starts with choosing the op mal gold standard for research on biomarkers; are sputum eosinophil counts the right measure to use? Several studies have shown that these cells in sputum can be used as a marker to tailor steroid treatment which leads to a lower exacerba on rate.17 More recent evidence shows that blood eosinophils are be er predictors of response to an -IL5 therapy18 or perios n as a predictor for response on an -IL13 therapy than sputum eosionphils are.19 This raises the ques on about the relevance of the body compartment where the in amma on is measured: blood, airway lumen, airway wall, small airways, or a combina on. If eosinophilic in amma on is present for example in both airway lumen and systemic circula on, there is an associa on with more severe asthma.20 Therefore, use of a single biomarker will probably discard the addi onal informa on of the extensiveness and loca on of in amma on.
SUMMARY AND GENERAL DISCUSSION
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