The Journal of allergy and clinical immunology
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J. Allergy Clin. Immunol. · Jun 2014
Somatic reversion in dedicator of cytokinesis 8 immunodeficiency modulates disease phenotype.
Autosomal recessive loss-of-function mutations in dedicator of cytokinesis 8 (DOCK8) cause a combined immunodeficiency characterized by atopy, recurrent infections, and cancer susceptibility. A genotype-phenotype explanation for the variable disease expression is lacking. ⋯ In patients with DOCK8 deficiency, only certain combinations of germline mutations supported secondary somatic repair. Those patients had an ameliorated disease course with longer survival but still had fatal complications or required hematopoietic cell transplantation. These observations support the concept that some DOCK8-immunodeficient patients have mutable mosaic genomes that can modulate disease phenotype over time.
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J. Allergy Clin. Immunol. · Jun 2014
Theophylline inhibits the cough reflex through a novel mechanism of action.
Theophylline has been used in the treatment of asthma and chronic obstructive pulmonary disease for more than 80 years. In addition to bronchodilator and anti-inflammatory activity, clinical studies have suggested that theophylline acts as an antitussive agent. Cough is the most frequent reason for consultation with a family doctor, and treatment options are limited. Determining how theophylline inhibits cough might lead to the development of optimized compounds. ⋯ Theophylline inhibits capsaicin-induced cough under both normal and "disease" conditions by decreasing the excitability of sensory nerves through activation of small- and intermediate-conductance calcium-activated potassium channels. These findings could lead to the development of optimized antitussive compounds with a reduced side effect potential.
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J. Allergy Clin. Immunol. · May 2014
Randomized Controlled Trial Multicenter StudyObesity and adiposity indicators, asthma, and atopy in Puerto Rican children.
Whether adiposity indicators other than body mass index (BMI) should be used in studies of childhood asthma is largely unknown. The role of atopy in "obese asthma" is also unclear. ⋯ Adiposity indicators are associated with asthma, asthma severity/control, and atopy in Puerto Rican children. Atopy significantly mediates the effect of adiposity on asthma outcomes. Longitudinal studies are needed to further investigate the causal role, if any, of adiposity distribution and atopy on "obese asthma" in childhood.
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J. Allergy Clin. Immunol. · May 2014
Multicenter Study Clinical TrialUnsupervised phenotyping of Severe Asthma Research Program participants using expanded lung data.
Previous studies have identified asthma phenotypes based on small numbers of clinical, physiologic, or inflammatory characteristics. However, no studies have used a wide range of variables using machine learning approaches. ⋯ The unsupervised machine learning approaches used here provide unique insights into disease, confirming other approaches while revealing novel additional phenotypes.