The Journal of allergy and clinical immunology
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J. Allergy Clin. Immunol. · Sep 2011
Decreased lung function after preschool wheezing rhinovirus illnesses in children at risk to develop asthma.
Preschool rhinovirus (RV) wheezing illnesses predict an increased risk of childhood asthma; however, it is not clear how specific viral illnesses in early life relate to lung function later on in childhood. ⋯ Among outpatient viral wheezing illnesses in early childhood, those caused by RV infections are the most significant predictors of decreased lung function up to age 8 years in a high-risk birth cohort. Whether low lung function is a cause and/or effect of RV wheezing illnesses is yet to be determined.
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J. Allergy Clin. Immunol. · Sep 2011
Effects of obesity and bariatric surgery on airway hyperresponsiveness, asthma control, and inflammation.
Asthma in obese subjects is poorly understood, and these patients are often refractory to standard therapy. ⋯ Bariatric surgery improves AHR in obese asthmatic patients with normal serum IgE levels. Weight loss has dichotomous effects on airway physiology and T-cell function typically involved in the pathogenesis of asthma, suggesting that obesity produces a unique phenotype of asthma that will require a distinct therapeutic approach.
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J. Allergy Clin. Immunol. · Sep 2011
ReviewEvidence of a genetic contribution to lung function decline in asthma.
There has been great progress in identifying new asthma susceptibility genes. In asthmatic subjects there is variable airway remodeling that includes features such as smooth muscle hypertrophy/hyperplasia, basement membrane thickening, and increased extracellular matrix deposition. Does airway remodeling have a genetic contribution in asthma? Data from different murine strains suggest there is a genetic contribution to the development and progression of airway remodeling. ⋯ To date, single nucleotide polymorphisms spanning ADAM33, ESR1, PLAUR, and VEGF have been associated with an excess decline in lung function in asthmatic subjects carrying the rare alleles (FEV(1), -13.0 to 55.2 mL/y excess). Interestingly these genes have overlapping functions in proteolytic pathways in the airways. There is accumulating evidence that genetic factors are important in the development of airway remodeling in asthmatic subjects, and further longitudinal studies with additional remodeling phenotypes and genome-wide association studies will identify novel susceptibility genes, leading to new approaches to target remodeling in asthmatic subjects.
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J. Allergy Clin. Immunol. · Sep 2011
ReviewPathophysiology of asthma: what has our current understanding taught us about new therapeutic approaches?
Current asthma therapy is based on the use of adrenergic bronchodilator and anti-inflammatory drugs the specificity, efficacy, duration of action, and safety of which have been derived through classical pharmacology and medicinal chemistry. That asthma is a T(H)2-type inflammatory disorder frequently associated with atopy and allergic comorbidities has led to a concentrated effort to find treatments that act selectively on this pathway. A systematic literature review was undertaken, as well as a review of the Web site Clinicaltrials.gov for ongoing trials. ⋯ A case is made for a different approach to drug discovery based on acquiring a greater understanding of asthma stratification, the relevant pathways involved, and the development of appropriate diagnostic tests enabling the targeting of selective treatments to those asthmatic phenotypes most likely to respond. The recognition that asthma is more than allergy mandates improved predictive animal models and an appreciation that many of the environmental insults that initiate, consolidate, and exacerbate asthma operate through an epithelium functioning in a disorderly fashion. An integrated model that places the epithelium at the forefront of asthma pathogenesis suggests that greater emphasis should be placed on therapeutics that increase the airways' resistance against the inhaled environment rather than focusing only on suppression of inflammation.
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J. Allergy Clin. Immunol. · Aug 2011
Associations among maternal childhood socioeconomic status, cord blood IgE levels, and repeated wheeze in urban children.
Independent of current socioeconomic status (SES), past maternal SES might influence asthma outcomes in children. ⋯ Lower maternal childhood SES was associated with increased cord blood IgE levels and repeated wheeze through both direct and indirect effects, providing new insights into the role of social inequalities as determinants of childhood respiratory risk.