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Emerging role of long acting muscarinic antagonists for asthma.

Acetlycholine is involved in the control of airway smooth muscle constriction and in recruitment of inflammatory cells via neuronal and paracrine effects on muscarinic type 3 receptors. Long acting muscarinic antagonists (LAMA) are well established in guidelines for COPD but are not currently licensed for use in asthma.

There are emerging data from key clinical trials to show that LAMA may confer bronchodilator effects and improved control when used in addition to inhaled corticosteroid (ICS) alone or in conjunction with long acting beta-agonists (LABA).

Further studies in persistent asthmatic patients are required to evaluate ICS sparing effects of LAMA looking particularly at airway hyper-responsiveness and surrogate inflammatory markers, in addition to evaluation of possible synergy between LAMA and LABA when given together.

Future possible development of combination inhalers comprising ICS/LAMA or ICS/LAMA/LABA will require long term studies looking at asthma control and exacerbations in both adult and pediatric patients.

Rhinovirus Wheezing Illness and Genetic Risk of Childhood-Onset Asthma.

Background Both genetic variation at the 17q21 locus and virus-induced respiratory wheezing illnesses are associated with the development of asthma. Our aim was to determine the effects of these two factors on the risk of asthma in the Childhood Origins of Asthma (COAST) and the Copenhagen Prospective Study on Asthma in Childhood (COPSAC) birth cohorts.

Methods We tested genotypes at the 17q21 locus for associations with asthma and with human rhinovirus (HRV) and respiratory syncytial virus (RSV) wheezing illnesses and tested for interactions between 17q21 genotypes and HRV and RSV wheezing illnesses with respect to the risk of asthma. Finally, we examined genotype-specific expression of 17q21 genes in unstimulated and HRV-stimulated peripheral-blood mononuclear cells (PBMCs).

Results The 17q21 variants were associated with HRV wheezing illnesses in early life, but not with RSV wheezing illnesses. The associations of 17q21 variants with asthma were restricted to children who had had HRV wheezing illnesses, resulting in a significant interaction effect with respect to the risk of asthma. Moreover, the expression levels of ORMDL3 and of GSDMB were significantly increased in HRV-stimulated PBMCs, as compared with unstimulated PBMCs. The expression of these genes was associated with 17q21 variants in both conditions, although the increase with exposure to HRV was not genotype-specific.

Conclusions Variants at the 17q21 locus were associated with asthma in children who had had HRV wheezing illnesses and with expression of two genes at this locus. The expression levels of both genes increased in response to HRV stimulation, although the relative increase was not associated with the 17q21 genotypes. (Funded by the National Institutes of Health.).

Characteristics of allergic sensitization among asthmatic adults older than 55 years: results from the National Health and Nutrition Examination Survey, 2005-2006.

BACKGROUND: Approximately 60% to 80% of children and young adults with asthma are sensitized to at least one allergen. In contrast, previous studies from specific subpopulations of older patients with asthma suggest that allergic sensitization is significantly lower in this age group. The prevalence and patterns of IgE-mediated sensitization have not been compared among a broad population of younger and older patients with asthma.

OBJECTIVE: To determine the prevalence and patterns of IgE-mediated sensitization among a broad population of younger and older patients with asthma.

METHODS: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2005-2006 to compare IgE-mediated sensitization rates between younger (20-40 years) and older (≥55 years) patients with current asthma. Atopy was defined as a detectable serum IgE to at least 1 allergen in a panel of 19 allergens. The associations among sensitization, current asthma, and asthma control measures (health care use and symptoms) were examined by logistic regression.

RESULTS: In a group of 2,573 patients, either 20 to 40 years of age or 55 years or older, 108 (6.7%) and 43 (4.5%) patients with current asthma were identified, respectively. Allergic sensitization rates among the adults with asthma differed only moderately and not statistically significantly between the age groups; 75.4% of the younger and 65.2% of the older asthmatic patients were sensitized to at least 1 allergen. The association between sensitization and markers of asthma control did not appear to differ among the age groups.

CONCLUSION: Allergic sensitization in older patients with asthma may be more common than previously reported.

AAAAI and ACAAI surveillance study of subcutaneous immunotherapy, Year 3: what practices modify the risk of systemic reactions?

OBJECTIVE: To define the incidence of and clinical practices associated with subcutaneous immunotherapy (SCIT)-related systemic reactions (SRs).

METHODS: From 2008-2011, American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma & Immunology members completed an annual survey of SCIT-related SRs of varying severity (with grade 1 indicating mild; grade 2, moderate; and grade 3, severe anaphylaxis). From 2010-2011 (year 3) data were collected regarding SCIT-related procedures, including screening of patients with asthma, dose adjustment during peak pollen seasons, build-up regimens (conventional, cluster, or rush), and premedication.

RESULTS: No fatal reactions were directly or indirectly reported from 2008-2011. The SR rates were similar for all 3 years (0.1% of injection visits; 83% of practices), as were severity grades. On average, for all 3 years, there were 7.1 grade 1, 2.6 grade 2, and 0.4 grade 3 SRs per 10,000 injection visits. Screening for worsening asthma symptoms was highly prevalent (86% always screened). Practices that always reduced doses during peak pollen season were significantly less likely to report grade 2 or 3 SRs (44% vs 65%; P = .04). Cluster and rush build-up were associated with significantly more SRs (P < .001). Practices that premedicated were significantly more likely to report grade 2 and 3 SRs (P < .01).

CONCLUSION: Fatal reactions to SCIT appear to be declining, possibly related to almost universal screening of asthmatic patients. Adjusting doses during the pollen season may be associated with decreased risk for severe SRs. Cluster and rush immunotherapy were associated with increased risk for SRs. Premedication by practices reporting SRs likely reflects past experience with SRs.

When are biomarkers required in the management of airway diseases?

Biomarkers are characteristics that are objectively measured and evaluated as indicators of biological or pathogenic processes, or responses to therapeutic interventions, and may provide information on the prognosis or progression of the disease and response to treatment. They are likely to be helpful in the management of airway diseases because of the heterogeneity of their pathobiology. Most biomarkers have been developed and evaluated to assess the airway inflammation (or bronchitis) associated with airway diseases. These include quantitative cell counts in sputum, fraction of nitric oxide in exhaled breath, and various metabolites in exhaled breath.

This review provides a brief description of these biomarkers with a particular emphasis on how eosinophil and neutrophil counts in sputum could be used to manage airway diseases such as asthma, chronic obstructive pulmonary disease, and chronic cough.

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