Airway inflammation during clinical remission of atopic asthma : effect of anti-inflammatory therapy

As stated in the introductory remarks, various questions arise from the epidemiological fact that a great deal of subjects with apparently outgrown asthma experiences a relapse of symptoms of asthma later in life. ln the present thesis, the next questions will be addressed: Are we able to produce convincing arguments of ongoing airway inflammation and/or remodeling in subjects who are believed to have outgrown their asthma? To address this question, we measured spirometry values, bronchial responsiveness to different inhaled stimuli, and exhaled nitric oxide levels in adolescents in clinical remission of atopic asthma. Clinical remission was defined as complete absence of symptoms without the use of any medication in the year preceding the study. Chapter 3 describes the results of this study, wherein subjects in clinical remission were compared with subjects with symptomatic asthma and healthy controls. In Chapter 4 invasively obtained "proof' of ongoing airway inflammation and remodeling during clinical remission of atopic asthma is discussed. By means of flexible bronchoscopy, biopsies were obtained from the airway walls in all subjects from the three study groups. A comparison of biopsy findings, including inflammatory cell type density and various indices of airway remodeling, was made between the groups. Also, data were compared with noninvasive markers of airway disease, such as exhaled nitric oxide levels and bronchial responsiveness to inhaled stimuli. 2 If persistent airway inflammation can be demonstrated during clinical remission, could blunted symptom perception explain the discrepancy between the lack of symptoms and ongoing disease? This question will be dealt with in chapter 5, where a study is described in which we obtained "BORG" dyspnea scores from subjects in clinical remission and subjects with symptomatic asthma during MCh and AMP provocation. 3 Would subjects with subclinical airway inflammation and remodelling benefit from antiinflammatory treatment in the short-term? In chapter 6, a double blind, longitudinal, placebo controlled study is described in which subjects in clinical remission of atopic asthma are treated for three months with either the salmeterol/flixotide propionate combination product (Seretide) or placebo. Again, invasive- as well as non-invasive indices were obtained from all subjects before and after treatment. 4 Asthma remission- does it exist? This question will be dealt with in chapter 7. Whether "true" remission of asthma can be reached with or without the aid of prolonged anti-inflammatory treatment is as yet unknown. A review of relevant literature as well as a proposal to deal with subjects with apparently outgrown asthma is given.

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