Fungus-induced obstructive airway disease in atopic individuals can be differentiated into two categories: first, uncomplicated asthmatic reactions due to high but transient exposure to fungal spores (fungal asthma), resulting in a TH2-type response with immunoglobulin E-mediated reactions and eosinophilic inflammation; and second, a more complex asthmatic reaction due to colonization of the mucus-epithelial surface by virulent protease-producing fungi. The latter condition stimulates as exaggerated immunological response including all subclasses of antibodies directed against the microorganism and an intense eosinophilic infiltrate of the airways. The authors propose that the exaggerated inflammatory response in allergic bronchopulmonary fungosis damages epithelial cells and underlying tissue cells, resulting in inefficient elimination of the microorganisms and damage to matrix proteins of the lung tissue by proteases released by both the fungi and degranulating eosinophils. The positive effects of corticosteroids in the treatment of allergic bronchopulmonary aspergillosis probably results from the dampening of the inflammatory response and an increase of the efficiency of killing the fungi. Sensitization to fungi is high in childhood and declines rapidly with age, suggesting that younger children may be less proficient in clearing fungi from the airways. We propose that insufficient treatment of fungal asthma may result in damage to the bronchial mucosa and formation of bronchiectasis.
Background Genome wide association studies (GWAS) of asthma have identified single nucleotide polymorphisms (SNPs) that modestly increase the risk for asthma. This could be due to phenotypic heterogeneity of asthma. Bronchial hyperresponsiveness (BHR) is a phenotypic hallmark of asthma. We aim to identify susceptibility genes for asthma combined with BHR and analyse the presence of cis-eQTLs among replicated SNPs. Secondly, we compare the genetic association of SNPs previously associated with (doctor diagnosed) asthma to our GWAS of asthma with BHR. Methods A GWAS was performed in 920 asthmatics with BHR and 980 controls. Top SNPs of our GWAS were analysed in four replication cohorts and lung cis-eQTL analysis was performed on replicated SNPs. We investigated association of SNPs previously associated with asthma in our data. Results 368 SNPs were followed up for replication. Six SNPs in genes encoding ABI3BP, NAF1, MICA and the 17q21 locus replicated in one or more cohorts, with one locus (17q21) achieving genome wide significance after meta-analysis. Five out of 6 replicated SNPs regulated 35 gene transcripts in whole lung. Eight of 20 asthma associated SNPs from previous GWAS were significantly associated with asthma and BHR. Three SNPs, in IL-33 and GSDMB, showed larger effect sizes in our data compared to published literature. Conclusions Combining GWAS with subsequent lung eQTL analysis revealed disease associated SNPs regulating lung mRNA expression levels of potential new asthma genes. Adding BHR to the asthma definition does not lead to an overall larger genetic effect size than analysing (doctor’s diagnosed) asthma.
The number of patients with allergic diseases in Europe, and thus relevant demand for health care, is continuously increasing. In this EAACI-UEMS position paper, a rationale is given for the medical specialty of allergology. General practitioners and general paediatricians usually cannot elucidate and address all causative factors. Throughout Europe, therefore, the expertise of allergologists (allergists) is required. In collaboration with other medical professionals, they take care of allergic patients, in private practices or in specialized public centres. A well-structured collaboration between allergists and allergy centres offers the possibility of rapid signalling of new trends developing in the population of allergic patients (e.g. in food and drug allergy). Allergy centres also can perform clinical (and basic) research, teach medical students, future allergists and provide postgraduate training. To prevent that the quality of care in one or several countries within Europe lags behind developments in other countries, the UEMS Section and Board on Allergology together with the European Academy of Allergy and Clinical Immunology advocates the status of a full specialty of allergology in each European country, with a further intention to align their activities (blueprint, curriculum and centre visitation) with the UEMS Section of Paediatrics.Allergology or allergology and clinical immunology are recognized as a full specialty in 12 European countries. It is a subspecialty in six other European countries. Some countries also recognize paediatric allergology as a full specialty or subspecialty. The UEMS (Union of European Medical Specialists) Section and Board (S&B) on Allergology has defined the focus of the specialty and requirements for training and education (Tables 1, 2, 3) (1) and collaborates with EAACI (European Academy of Allergy and Clinical Immunology) in allergy knowledge examinations, education programmes and advocates for the specialty. UEMS S&B has recently started onsite visitation of allergy training centres in Europe. Several recent developments are changing the position of the allergist in Europe: (i) firstly, the large increase in knowledge about the immunological processes that play a role in allergic diseases. This increase in knowledge has led to changes in diagnostic and therapeutic possibilities (e.g. new forms of immunotherapy, component-resolved diagnosis), and it is expected that this tendency will continue; (ii) secondly, the
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