Cysteinyl Leukotrienes Pathway Genes, Atopic Asthma and Drug Response: From Population Isolates to Large Genome-Wide Association Studies.

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Cysteinyl Leukotrienes Pathway Genes, Atopic Asthma and Drug Response: From Population Isolates to Large Genome-Wide Association Studies.

Front Pharmacol. 2016;7:299

Authors: Thompson MD, Capra V, Clunes MT, Rovati GE, Stankova J, Maj MC, Duffy DL

Abstract
Genetic variants associated with asthma pathogenesis and altered response to drug therapy are discussed. Many studies implicate polymorphisms in genes encoding the enzymes responsible for leukotriene synthesis and intracellular signaling through activation of seven transmembrane domain receptors, such as the cysteinyl leukotriene 1 (CYSLTR1) and 2 (CYSLTR2) receptors. The leukotrienes are polyunsaturated lipoxygenated eicosatetraenoic acids that exhibit a wide range of pharmacological and physiological actions. Of the three enzymes involved in the formation of the leukotrienes, arachidonate 5 lipoxygenase 5 (ALOX5), leukotriene C4 synthase (LTC4S), and leukotriene hydrolase (LTA4H) are all polymorphic. These polymorphisms often result in variable production of the CysLTs (LTC4, LTD4, and LTE4) and LTB4. Variable number tandem repeat sequences located in the Sp1-binding motif within the promotor region of the ALOX5 gene are associated with leukotriene burden and bronchoconstriction independent of asthma risk. A 444A > C SNP polymorphism in the LTC4S gene, encoding an enzyme required for the formation of a glutathione adduct at the C-6 position of the arachidonic acid backbone, is associated with severe asthma and altered response to the CYSLTR1 receptor antagonist zafirlukast. Genetic variability in the CysLT pathway may contribute additively or synergistically to altered drug responses. The 601 A > G variant of the CYSLTR2 gene, encoding the Met201Val CYSLTR2 receptor variant, is associated with atopic asthma in the general European population, where it is present at a frequency of ?2.6%. The variant was originally found in the founder population of Tristan da Cunha, a remote island in the South Atlantic, in which the prevalence of atopy is approximately 45% and the prevalence of asthma is 36%. In vitro work showed that the atopy-associated Met201Val variant was inactivating with respect to ligand binding, Ca(2+) flux and inositol phosphate generation. In addition, the CYSLTR1 gene, located at Xq13-21.1, has been associated with atopic asthma. The activating Gly300Ser CYSLTR1 variant is discussed. In addition to genetic loci, risk for asthma may be influenced by environmental factors such as smoking. The contribution of CysLT pathway gene sequence variants to atopic asthma is discussed in the context of other genes and environmental influences known to influence asthma.

PMID: 27990118 [PubMed – in process]

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Association of interleukin-18 and asthma.

Association of interleukin-18 and asthma.

Inflammation. 2016 Dec 02;

Authors: Xu MH, Yuan FL, Wang SJ, Xu HY, Li CW, Tong X

Abstract
Cytokine-mediated immunity plays a dominant role in the pathogenesis of various immune diseases, including asthma. The recent identification of the family interleukin (IL)-1-related cytokine IL-18 now contributes to our understanding of the fine-tuning of cellular immunity. IL-18 can act as a cofactor for Th2 cell development and IgE production and also plays an important role in the differentiation of Th1 cells. Recent work identified an IL-18 association with the pathogenesis of asthma, wherein increased IL-18 expression was found in the serum of patients. Furthermore, IL-18 polymorphisms with susceptibility to asthma were reported, suggesting that IL-18 may be therapeutically relevant to asthma. In this review, we discuss the role of IL-18 in the pathogenesis of asthma and its therapeutic potential based on current research.

PMID: 27913952 [PubMed – as supplied by publisher]

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Association of Allergic Rhinitis and Sinusitis with Childhood Asthma.

Association of Allergic Rhinitis and Sinusitis with Childhood Asthma.

Indian Pediatr. 2016 Nov 5;:

Authors: Kumar S, Singh M, Das RR, Mathew JL, Saxena AK

Abstract
BACKGROUND: To study the point prevalence of allergic rhinitis and sinusitis in childhood asthma and to examine the relationships among them.
METHODS: In 250 children (age <13 y) with mild-to-moderte asthma, allergic rhinitis was diagnosed by clinical plus nasal eosinophilia criteria, and sinusitis was diagnosed clinically plus confirmation by computerized tomography scan.
RESULTS: The point prevalence of allergic rhinitis was 13.6%, and of sinusitis was 2%. On multivariate analysis, allergic rhinitis, sinusitis, and family history were significantly associated with asthma severity.
CONCLUSION: Allergic rhinitis is common in childhood, but sinusitis is rare.

PMID: 27889716 [PubMed – as supplied by publisher]

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American Lung Association in Nebraska: Kids With Asthma Can Attend Asthma Camp for Free – Marketwired (press release)

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Marketwired (press release)
OMAHA, NE–(Marketwired – May 31, 2016) – Both parents and kids with asthma can breathe easy this summer thanks to the American Lung Association's Camp Superkids, a weeklong summer camp exclusively for youth ages 7-17 that teaches them how to …

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Girl Scouts of Southern Illinois unveils new Asthma Awareness Patch Program at American Lung Association event – RiverBender.com


RiverBender.com

Girl Scouts of Southern Illinois unveils new Asthma Awareness Patch Program at American Lung Association event
RiverBender.com
GLEN CARBON – Girl Scouts of Southern Illinois (GSSI) introduced a new Asthma Awareness patch on Saturday, May 7 at Glazebrook Park in Godfrey in conjunction with the 16th Annual American Lung Association Asthma Awareness and Education Walk.

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Effect of prenatal supplementation with vitamin D on asthma or recurrent wheezing in offspring by age 3 years – Pharmacy Today, American Pharmacists Association, pharmacist.com


JAMA: The Journal of the American Medical Association

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Pharmacy Today, American Pharmacists Association, pharmacist.com
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Effect of Prenatal Supplementation With Vitamin D on Asthma or Recurrent Wheezing in Offspring by Age 3 Years: The … – JAMA: The Journal of the American Medical Association


JAMA: The Journal of the American Medical Association

Effect of Prenatal Supplementation With Vitamin D on Asthma or Recurrent Wheezing in Offspring by Age 3 Years: The
JAMA: The Journal of the American Medical Association
Importance Asthma and wheezing begin early in life, and prenatal vitamin D deficiency has been variably associated with these disorders in offspring. Objective To determine whether prenatal vitamin D (cholecalciferol) supplementation can prevent asthma
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