Asthma phenotypes have been developed to address the complexities of the disease. However, owing to a lack of longitudinal studies, little is known about the onset as well as the stability of phenotypes. Distinguishing phenotypes with regard to the severity or duration of the disease is essential. A phenotype covers the clinically relevant properties of the disease, but does not show the direct relationship to disease etiology and pathophysiology. Different pathogenetic mechanisms might cause similar asthma symptoms and might be operant in a certain phenotype. These putative mechanisms are addressed by the term ‘endotype’. Classification of asthma based on endotypes provides advantages for epidemiological, genetic, and drug-related studies. A successful definition of endotypes should link key pathogenic mechanisms with the asthma phenotype. Thus, the identification of corresponding molecular biomarkers for individual pathogenic mechanism underlying phenotypes or subgroups within a phenotype is important. Whether newly defined asthma endotypes predict the individual course of asthma has to be validated in longitudinal studies. The accurate endotyping reflects natural history of asthma and should help to predict treatment response. Thus, understanding asthma endotypes might be useful in clinical practice.

The concept of disease modification has been introduced to define the therapeutic strategies aimed to break, stop, or reverse the natural course of a chronic invalidating disease. This strategy is tightly related to the biomarker-based stratification of affected patients using genetic and other biological markers. With regard to the progress in understanding the genetic background of atopic dermatitis (AD), its natural history and its pivotal role in the emergence of allergic asthma, the time is mature to foster the research field of biomarkers in AD and to consider the elaboration of disease-modifying strategies in the management of AD with the goal to stop or even reverse the atopic march.

BackgroundThe incidence of asthma and obesity is increasing worldwide, and reports suggest that obese patients have more severe asthma. We investigated whether obese asthma patients have more severe airway obstruction and airway hyper-responsiveness and a different type of airway inflammation than lean asthmatics. Furthermore, we assessed the effect of obesity on corticosteroid treatment response.MethodsPatient data from four well-documented asthma cohorts were pooled (n = 423). We evaluated FEV1, bronchial hyper-responsiveness (PC20) to either methacholine/histamine or adenosine 5′-monophosphate (AMP) (differential) cell counts in induced sputum and blood and corticosteroid treatment response in 118 patients.ResultsAt baseline, FEV1, PC20 methacholine or histamine, and PC20AMP values were comparable in 63 obese (BMI ≥30 kg/m2) and 213 lean patients (BMI <25 kg/m2). Obese patients had significantly higher blood neutrophils. These higher blood neutrophils were only seen in obese women and not in obese men. After a two-week treatment with corticosteroids, we observed less corticosteroid-induced improvement in FEV1%predicted in obese patients than in lean patients (median 1.7% vs 6.3% respectively, P = 0.04). The percentage of sputum eosinophils improved significantly less with higher BMI (P = 0.03), and the number of blood neutrophils increased less in obese than in lean patients (0.32 x103/μl vs 0.57 x103/μl, P = 0.046).ConclusionsWe found no differences in asthma severity between obese and nonobese asthmatics. Interestingly, obese patients demonstrated more neutrophils in sputum and blood than nonobese patients. The smaller improvement in FEV1 and sputum eosinophils suggests a worse corticosteroid treatment response in obese asthmatics.

BackgroundThe hormonal form of vitamin D affects both adaptive and innate immune functions involved in the development of allergies. Certain genotypes have been seen to alter the association between vitamin D deficiency (VDD) and the risk of food sensitization in children.MethodsWe examined 27 functional single nucleotide polymorphisms (SNPs) in/near selected candidate genes for association with total immunoglobulin E (IgE) and effect modification by 25-hydroxyvitamin D in the 1958 British birth cohort (aged 45 years, n = 4921). A cut-off value of 50 nmol/L was used to define VDD.ResultsFour SNPs (in FCER1A,IL13, and CYP24A1) and three SNPs (in IL4 and CYP24A1) were associated with total IgE and specific IgE, respectively, after correction for multiple testing. As in a previous study, MS4A2 (rs512555, Pinteraction = 0.04) and IL4 (rs2243250, Pinteraction = 0.02), and their composite score (Pinteraction = 0.009) modified the association between VDD and allergy-related outcome. Vitamin D deficiency was associated with higher total IgE only in the carriers of the ‘C’ allele (IL4), which is present in 86% of white Europeans, while only 26% of Chinese and <20% of some African populations are carriers.ConclusionsOur study on white European adults was consistent with a previous study on children from largely non-white ethnic groups, suggesting that IL4 and MS4A2 genotypes modify the association between VDD and allergy risk. The risk allele in IL4 is present in nearly 90% of white Europeans, while less than a quarter are carriers in some other populations, highlighting the need to consider possible ethnic differences in allergy-related responsiveness to VDD.