| Attenuated P2X7 pore function as a risk factor for virus-induced loss of asthma control. | |
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MedLine Citation:
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PMID: 19201928 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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RATIONALE: Upper respiratory tract infection is a guideline accepted risk domain for the loss of asthma control. The ionotrophic nucleotide receptor P2X(7) regulates compartmentalized acute inflammation and the immune response to airway pathogens. OBJECTIVES: We hypothesized that variability in P2X(7) function contributes to neutrophilic airway inflammation during a cold and thereby is linked to acute asthma. METHODS: Research volunteers with asthma were enrolled at the onset of a naturally occurring cold and monitored through convalescence, assessing symptoms, lung function, and airway inflammation. P2X(7) pore activity in whole blood samples was measured using a genomically validated flow cytometric assay. MEASUREMENTS AND MAIN RESULTS: Thirty-five participants with mild to moderate allergic asthma were enrolled and 31 completed all visits. P2X(7) pore function correlated with the change in nasal lavage neutrophil counts during the cold (R(s) = 0.514, P = 0.004) and was inversely related to the change in asthma symptoms (R(s) = -0.486, P = 0.009). The change in peak expiratory flow recordings, precold use of inhaled corticosteroids, and P2X(7) pore function were multivariate predictors of asthma symptoms (P = 0.001, < 0.001 and = 0.003 respectively). Attenuated P2X(7) activity was associated with the risk of losing asthma control (crude odds ratio, 11.0; 95% confidence interval, 1.1-106.4) even after adjustment for inhaled corticosteroids and rhinovirus (odds ratio, 15.0). CONCLUSIONS: A whole blood P2X(7) pore assay robustly identifies participants with loss-of-function genotypes. Using this assay as an epidemiologic tool, attenuated P2X(7) pore activity may be a novel biomarker of virus-induced loss of asthma control. |
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Authors:
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Loren C Denlinger; Lei Shi; Arturo Guadarrama; Kathy Schell; Dawn Green; Alison Morrin; Kirk Hogan; Ronald L Sorkness; William W Busse; James E Gern |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2008-11-21 |
Journal Detail:
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Title: American journal of respiratory and critical care medicine Volume: 179 ISSN: 1535-4970 ISO Abbreviation: Am. J. Respir. Crit. Care Med. Publication Date: 2009 Feb |
Date Detail:
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Created Date: 2009-02-09 Completed Date: 2009-02-24 Revised Date: 2010-09-23 |
Medline Journal Info:
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Nlm Unique ID: 9421642 Medline TA: Am J Respir Crit Care Med Country: United States |
Other Details:
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Languages: eng Pagination: 265-70 Citation Subset: AIM; IM |
Affiliation:
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Section of Allergy, Pulmonary, and Critical Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, P.O. Box 9988, Madison, WI 53792, USA. ldenling@wisc.edu |
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| MeSH Terms | |
Descriptor/Qualifier:
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Adrenal Cortex Hormones
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administration & dosage Albuterol / administration & dosage Asthma / blood, drug therapy, immunology* Biological Markers / blood Bronchitis / immunology, virology Bronchodilator Agents / administration & dosage Common Cold / immunology, virology* Flow Cytometry / methods Humans Ion Channel Gating / immunology* Nasal Lavage Fluid / immunology Neutrophils / immunology Nuclear Pore / immunology Odds Ratio Peak Expiratory Flow Rate / immunology Receptors, Purinergic P2 / blood, immunology* Risk Factors Virus Diseases / complications* |
| Grant Support | |
ID/Acronym/Agency:
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K12 RR01761401/RR/NCRR NIH HHS; K23 HL081492/HL/NHLBI NIH HHS; P01 AI5050001/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Adrenal Cortex Hormones; 0/Biological Markers; 0/Bronchodilator Agents; 0/Receptors, Purinergic P2; 0/purinergic P2X7 receptor; 18559-94-9/Albuterol |
| Comments/Corrections | |
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