Maternal microchimerism protects against the development of asthma
Department of Human Genetics, University of Chicago, Chicago, Ill. Electronic address: .The Journal of allergy and clinical immunology (Impact Factor: 11.48). 02/2013; 132(1). DOI: 10.1016/j.jaci.2012.12.1575
BACKGROUND: Maternal asthma and child's sex are among the most significant and reproducible risk factors for the development of asthma. Although the mechanisms for these effects are unknown, they likely involve nonclassical genetic mechanisms. One such mechanism could involve the transfer and persistence of maternal cells to her offspring, a common occurrence known as maternal microchimerism (MMc). MMc has been associated with many autoimmune diseases but has not been investigated for a role in asthma or allergic disease. OBJECTIVE: We hypothesized that some of the observed risks for asthma may be due to different rates of transmission or persistence of maternal cells to children of mothers with asthma compared with children of mothers without asthma, or to sons compared with daughters. We further hypothesized that rates of MMc differ between children with and without asthma. METHODS: We tested these hypotheses in 317 subjects from 3 independent cohorts by using a real-time quantitative PCR assay to detect a noninherited HLA allele in the child. RESULTS: MMc was detected in 20.5% of the subjects (range 16.8%-27.1% in the 3 cohorts). We observed lower rates of asthma among MMc-positive subjects than among MMc-negative subjects (odds ratio, 0.38; 95% CI, 0.19-0.79; P = .029). Neither maternal asthma nor sex of the child was a significant predictor of MMc in the child (P = .81 and .15, respectively). CONCLUSIONS: Our results suggest for the first time that MMc may protect against the development of asthma.
Article: Childhood asthma[Show abstract] [Hide abstract]
ABSTRACT: The purpose of this review is to provide an update on childhood asthma specifically related to the underlying genetic background and pathophysiology of asthma and their interaction with environmental stimuli. We will also discuss emerging data in the field of disease phenotyping. The field of genetics is continuously evolving to expand our knowledge on the cause of disease. Childhood onset asthma has been related to atopy and exposure to early-life infections. More recently, phenotypes have been used to classify asthma as transient and persistent, but the association of each phenotype with the genetic origin of asthma is not clearly understood. This review covers the topics of genetics, epigenetics, pathophysiology, phenotypes and treatment as they relate to childhood asthma. Overall, it provides a basis for the future of asthma treatment through description of the current research.Current opinion in pulmonary medicine 11/2013; 20(1). DOI:10.1097/MCP.0000000000000014 · 2.76 Impact Factor
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ABSTRACT: Last year's “Advances in pediatric asthma: moving toward asthma prevention” concluded that “We are well on our way to creating a pathway around wellness in asthma care and also to utilize new tools to predict the risk for asthma and take steps to not only prevent asthma exacerbations but also to prevent the early manifestations of the disease and thus prevent its evolution to severe asthma.” This year's summary will focus on recent advances in pediatric asthma on prenatal and postnatal factors altering the natural history of asthma, assessment of asthma control, and new insights regarding potential therapeutic targets for altering the course of asthma in children, as indicated in Journal of Allergy and Clinical Immunology publications in 2013 and early 2014. Recent reports continue to shed light on methods to understand factors that influence the course of asthma, methods to assess and communicate levels of control, and new targets for intervention, as well as new immunomodulators. It will now be important to carefully assess risk factors for the development of asthma, as well as the risk for asthma exacerbations, and to improve the way we communicate this information in the health care system. This will allow parents, primary care physicians, specialists, and provider systems to more effectively intervene in altering the course of asthma and to further reduce asthma morbidity and mortality.The Journal of allergy and clinical immunology 03/2014; 133(3):654–661. DOI:10.1016/j.jaci.2014.01.012 · 11.48 Impact Factor
Article: Asthma and the otolaryngologist[Show abstract] [Hide abstract]
ABSTRACT: Background Asthma is a chronic inflammatory disease of the lower airway that is commonly encountered by the otolaryngologist. This article provides information on how to recognize patients with asthma and discuss issues related to diagnosis, treatment, and continued management within the context of current guidelines. MethodsA literature review was conducted and relevant sources are referenced concerning the epidemiology of asthma, the pathophysiology of asthma, diagnostic strategies, treatment options, and continued management. ResultsAsthma is a common condition worldwide and is often associated with other atopic diseases such as allergic rhinitis and eczema, though other genetic and environmental factors appear to be important as well. The lower airway and upper airways share similar histology, as well as patterns of inflammation in response to environmental triggers. The diagnosis of asthma involves a careful history and a complete physical exam, including auscultation of the lungs and pulmonary function testing. Pharmacotherapy represents the primary method of treating asthma, though current evidence supports a positive role for antigen-specific immunotherapy for both prevention and treatment. Guidelines are available that can assist the otolaryngologist in classifying the severity of asthma, determining the level of control and recommending modifications in the treatment plan. Conclusion As airway specialists, otolaryngologists are in a unique position to recognize and manage asthma in their patients, particularly those with allergic disease. Maintaining a high index of suspicion and understanding the key elements of diagnosis and treatment are extremely important in order to achieve this goal. (C) 2014 ARS-AAOA, LLC.International Forum of Allergy and Rhinology 09/2014; 4 Suppl 2(S2):S70-3. DOI:10.1002/alr.21386 · 2.37 Impact Factor
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