Selective IgA Deficiency

Immunoglobulin A (IgA) deficiency is the most common primary immunodeficiency defined as decreased serum level of IgA in the presence of normal levels of other immunoglobulin isotypes. Most individuals with IgA deficiency are asymptomatic and identified coincidentally. However, some patients may present with recurrent infections of the respiratory and gastrointestinal tracts, allergic disorders, and autoimmune manifestations. Although IgA is the most abundant antibody isotype produced in the body, its functions are not clearly understood. Subclass IgA1 in monomeric form is mainly found in the blood circulation, whereas subclass IgA2 in dimeric form is the dominant immunoglobulin in mucosal secretions. Secretory IgA appears to have prime importance in immune exclusion of pathogenic microorganisms and maintenance of intestinal homeostasis. Despite this critical role, there may be some compensatory mechanisms that would prevent disease manifestations in some IgA-deficient individuals. In IgA deficiency, a maturation defect in B cells to produce IgA is commonly observed. Alterations in transmembrane activator and calcium modulator and cyclophilin ligand interactor gene appear to act as disease-modifying mutations in both IgA deficiency and common variable immunodeficiency, two diseases which probably lie in the same spectrum. Certain major histocompatibility complex haplotypes have been associated with susceptibility to IgA deficiency. The genetic basis of IgA deficiency remains to be clarified. Better understanding of the production and function of IgA is essential in elucidating the disease mechanism in IgA deficiency

Adaptation of a difficult to manage asthma programme for implementation in the Dutch context: a modified e-Delphi

Contains fulltext : 177900.pdf (publisher's version ) (Open Access)Patients with difficult-to-manage asthma represent a heterogeneous subgroup of asthma patients who require extensive assessment and tailored management. The International Primary Care Respiratory Group approach emphasises the importance of differentiating patients with asthma that is difficult to manage from those with severe disease. Local adaptation of this approach, however, is required to ensure an appropriate strategy for implementation in the Dutch context. We used a modified three-round e-Delphi approach to assess the opinion of all relevant stakeholders (general practitioners, pulmonologists, practice nurses, pulmonary nurses and people with asthma). In the first round, the participants were asked to provide potentially relevant items for a difficult-to-manage asthma programme, which resulted in 67 items. In the second round, we asked participants to rate the relevance of specific items on a seven-point Likert scale, and 46 items were selected as relevant. In the third round, the selected items were categorised and items were ranked within the categories according to relevance. Finally, we created the alphabet acronym for the categories 'the A-I of difficult-to-manage asthma' to resonate with an established Dutch 'A-E acronym for determining asthma control'. This should facilitate implementation of this programme within the existing structure of educational material on asthma and chronic obstructive pulmonary disease (COPD) in primary care, with potential for improving management of difficult-to-manage asthma. Other countries could use a similar approach to create a locally adapted version of such a programme

The burden of exacerbations in mild asthma: a systematic review.

Background: Although most patients with asthma have mild disease, data on how mild asthma is defined, and how frequently exacerbations occur in this patient population are scarce, so we aimed to redress this. Methods: We searched Medline and Medline In-Process (PubMed), and Embase in OVID for English-language publications containing "mild asthma" plus at least one relevant therapy and outcome/keyword, limited to randomised controlled trials (RCTs) and observational studies published between January 1990 and February 2019. Publications were filtered to ensure appropriate data extraction. The main outcomes were the definitions of mild asthma and exacerbations, baseline exacerbation rates and exacerbation data for placebo recipients in prospective studies. Meta-analysis of exacerbation rates was planned. Findings: Of 4064 articles identified, 64 were included in our review (49 743 subjects); 54 RCTs and 10 observational/other studies. Six main types of definitions of mild asthma were identified. While care was taken to ensure inclusion only of patients with mild asthma, marked heterogeneity was revealed in the definitions of mild asthma and hence the study populations. Reporting of exacerbations also varied widely between studies, precluding meta-analysis. Between 0-22% of patients were hospitalised for asthma or had a severe exacerbation in the previous year, according to baseline data from prospective studies. In RCTs, severe exacerbation rates in placebo recipients taking only short-acting β2-agonist therapy ranged from 0.20-2.88 per year. Conclusions: These data provide new evidence of the burden of exacerbations in mild asthma and highlight the need for standardised definitions of mild asthma and of exacerbations to progress further research