[Show abstract][Hide abstract] ABSTRACT: Background:
Asthma is a heterogeneous disease and development of novel therapeutics requires an understanding of pathophysiologic phenotypes. The purpose of the ADEPT study was to correlate clinical features and biomarkers with molecular characteristics, by profiling asthma (NCT01274507). This report presents for the first time the study design, and characteristics of the recruited subjects.
Patients with a range of asthma severity and healthy non-atopic controls were enrolled. The asthmatic subjects were followed for 12 months. Assessments included history, patient questionnaires, spirometry, airway hyper-responsiveness to methacholine, fractional exhaled nitric oxide (FENO), and biomarkers measured in induced sputum, blood, and bronchoscopy samples. All subjects underwent sputum induction and 30 subjects/cohort had bronchoscopy.
Mild (n = 52), moderate (n = 55), severe (n = 51) asthma cohorts and 30 healthy controls were enrolled from North America and Western Europe. Airflow obstruction, bronchodilator response and airways hyperresponsiveness increased with asthma severity, and severe asthma subjects had reduced forced vital capacity. Asthma control questionnaire-7 (ACQ7) scores worsened with asthma severity. In the asthmatics, mean values for all clinical and biomarker characteristics were stable over 12 months although individual variability was evident. FENO and blood eosinophils did not differ by asthma severity. Induced sputum eosinophils but not neutrophils were lower in mild compared to the moderate and severe asthma cohorts.
The ADEPT study successfully enrolled asthmatics across a spectrum of severity and non-atopic controls. Clinical characteristics were related to asthma severity and in general asthma characteristics e.g. lung function, were stable over 12 months. Use of the ADEPT data should prove useful in defining biological phenotypes to facilitate personalized therapeutic approaches.
Respiratory research 11/2015; 16(1):142. DOI:10.1186/s12931-015-0299-y · 3.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Breathing difficulties during exertion may be caused by exercise-induced laryngeal obstruction (EILO). The diagnosis depends on visualization of the larynx during exercise, i.e. by continuous laryngoscopic exercise (CLE) test. In case of severe supraglottic collapse and pronounced symptoms during strenuous exertion, surgical treatment (supraglottoplasty) has been suggested. The aims of this study were to evaluate outcome and patient satisfaction after supraglottoplasty for EILO and to compare our results with previously reported data. During the period December 2010 to October 2013, 17 patients diagnosed with moderate to severe supraglottic EILO were treated by supraglottoplasty with microlaryngoscopic laser technique at our institutions. The severity of patients symptoms (VAS score) and CLE scores was evaluated pre- and postoperatively. We found a decrease in patients symptoms from median 80 points VAS score preoperatively to 20 points postoperatively (p < 0.001) and a decrease in CLE sum score from median 4.0 points to 2.5 points (p < 0.05). Several previous studies have recommended surgery for selected patients with supraglottic involvement, but these have mainly been based on case reports or on very few patients. This study is the second larger-scale study that documents the positive effect of supraglottoplasty as treatment of EILO in terms of reduced respiratory symptoms and decreased laryngeal obstruction assessed by post-operative CLE test. We suggest that surgery is a well-tolerated and effective treatment option for selected EILO patients with moderate to severe supraglottic obstruction during exercise and a high level of physical activity
Archives of Oto-Rhino-Laryngology 11/2015; DOI:10.1007/s00405-015-3823-2 · 1.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Allergen-specific immunotherapy is the only curative treatment for type I allergy. It can be administered subcutaneously (SCIT) or sublingually (SLIT). The clinical efficacy of these two treatment modalities appears to be similar, but potential differences in the immunological mechanisms involved have not been fully explored.
To compare changes in the allergen-specific T cell response induced by subcutaneous versus sublingual administration of allergen-specific immunotherapy (AIT).
Grass pollen allergic patients were randomized into groups receiving either SCIT injections, or SLIT tablets or neither. PBMC were tested for Timothy grass (TG)-specific cytokine production by ELISPOT after in vitro expansion with TG peptide pools. Phenotypic characterization of cytokine producing cells was performed by FACS.
In the SCIT group, decreased IL-5 production was observed starting 10 months after treatment was commenced. At 24 months, T cell responses showed IL-5 levels significantly below the before treatment baseline. No significant reduction of IL-5 was observed in the SLIT or untreated group. However, a significant transient increase in IL-10 production after 10 months of treatment compared to baseline was detected in both treatment groups. FACS analysis revealed that IL-10 production was associated with CD4(+) T cells that also produced IFNγ, and therefore may be associated with an IL-10-secreting type 1 cell phenotype.
Conclusion and clinical relevance:
The most dominant immunological changes on a cellular level was a decrease in IL-5 in the SCIT group and a significant, transient increase of IL-10 observed after 10 months of treatment in both treated groups. The distinct routes of AIT administration may induce different immune-modulatory mechanisms at the cellular level. This article is protected by copyright. All rights reserved.