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Metrics of salbutamol use as predictors of future adverse outcomes in asthma.

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Metrics of salbutamol use as predictors of future adverse outcomes in asthma.

Clin Exp Allergy. 2013 Oct;43(10):1144-51

Authors: Patel M, Pilcher J, Reddel HK, Pritchard A, Corin A, Helm C, Tofield C, Shaw D, Black P, Weatherall M, Beasley R

Abstract
BACKGROUND: Beta-agonist overuse is associated with adverse outcomes in asthma, however, the relationships between different metrics of salbutamol use and future risk are uncertain.
OBJECTIVE: To investigate the relationship between metrics of salbutamol use and adverse outcome.
METHODS: In a 24-week randomized controlled trial of 303 asthma patients at risk of severe exacerbations which compared the efficacy and safety of combination budesonide/formoterol inhaler according to a single inhaler regimen (SMART) with a fixed-dose regimen with salbutamol as reliever ('Standard'), actual medication use was measured by electronic monitoring (Australian New Zealand Clinical Trials Registry Number ACTRN12610000515099). A nested cohort study explored the relationship between metrics of baseline salbutamol use over 2 weeks and future severe asthma exacerbations, poor asthma control (ACQ-5 ≥ 1.5) or 'extreme' salbutamol overuse (> 32 salbutamol actuations/24-h period).
RESULTS: Higher mean daily salbutamol use (per two actuations/day) [Odds ratio (OR) (95% CI) 1.24 (1.06-1.46)], higher days of salbutamol use (per 2 days in 2 weeks) [OR 1.15 (1.00-1.31)] and higher maximal 24-h use (per two actuations/day) [OR 1.09 (1.02-1.16)] were associated with future severe exacerbations. Higher mean daily salbutamol use was associated with future poor asthma control [OR 1.13 (1.02-1.26)]. Higher mean daily salbutamol use [OR 2.73 (1.84-4.07)], number of days of use [OR 1.46 (1.24-1.71)], and maximal daily use [OR 1.57 (1.31-1.89)] were associated with an increased risk of future extreme salbutamol overuse.
CONCLUSION AND CLINICAL RELEVANCE: Electronically recorded frequency of current salbutamol use is a strong predictor of risk of future adverse outcomes in asthma, with average daily use performing the best. These findings provide new information for clinicians considering metrics of salbutamol as predictors of future adverse outcomes in asthma.

PMID: 24074332 [PubMed - in process]

Sensitization to food and inhalant allergens in relation to age and wheeze among children with atopic dermatitis: Clinical Mechanisms in Allergic Disease.

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Sensitization to food and inhalant allergens in relation to age and wheeze among children with atopic dermatitis: Clinical Mechanisms in Allergic Disease.

Clin Exp Allergy. 2013 Oct;43(10):1160-70

Authors: Wisniewski JA, Agrawal R, Minnicozzi S, Xin W, Patrie J, Heymann PW, Workman L, Platts-Mills TA, Song TW, Moloney M, Woodfolk JA

Abstract
BACKGROUND: Atopic dermatitis (AD) is common in children; however, persistence of AD with or without asthma is less common. Longitudinal studies remain limited in their ability to characterize how IgE antibody responses evolve in AD, and their relationship with asthma.
OBJECTIVE: To use a cross-sectional study design of children with active AD to analyse age-related differences in IgE antibodies and relation to wheeze.
METHODS: IgE antibodies to food and inhalant allergens were measured in children with active AD (5 months to 15 years of age, n = 66), with and without history of wheeze.
RESULTS: Whereas IgE antibodies to foods persisted at a similar prevalence and titre throughout childhood, IgE antibodies to all aeroallergens rose sharply into adolescence. From birth, the chance of sensitization for any aeroallergen increased for each 12-month increment in age (OR ≥ 1.21, P < 0.01), with the largest effect observed for dust mite (OR = 1.56, P < 0.001). A steeper age-related rise in IgE antibody titre to dust mite, but no other allergen was associated with more severe disease. Despite this, sensitization to cat was more strongly associated with wheeze (OR = 4.5, P < 0.01), and linked to Fel d 1 and Fel d 4, but not Fel d 2. Comparison of cat allergic children with AD to those without, revealed higher IgE levels to Fel d 2 and Fel d 4 (P < 0.05), but not Fel d 1.
CONCLUSIONS AND CLINICAL RELEVANCE: Differences in sensitization to cat and dust mite among young children with AD may aid in identifying those at increased risk for disease progression and development of asthma. Early sensitization to cat and risk for wheeze among children with AD may be linked to an increased risk for sensitization to a broader spectrum of allergen components from early life. Collectively, our findings argue for early intervention strategies designed to mitigate skin inflammation in children with AD.

PMID: 24074334 [PubMed - in process]

Maternal 25-hydroxyvitamin D and its association with childhood atopic outcomes and lung function.

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Maternal 25-hydroxyvitamin D and its association with childhood atopic outcomes and lung function.

Clin Exp Allergy. 2013 Oct;43(10):1180-8

Authors: Wills AK, Shaheen SO, Granell R, Henderson AJ, Fraser WD, Lawlor DA

Abstract
BACKGROUND: It has been suggested that maternal vitamin D status in pregnancy influences the risk of asthma and atopy in the offspring. The epidemiological evidence to support these claims is conflicting and may reflect chance findings and differences in how vitamin D was assessed.
OBJECTIVE: To examine the association between blood total maternal 25-hydroxy vitamin D (25(OH)D) concentrations in pregnancy and offspring asthma, atopy and lung function in the largest birth cohort study to date.
METHODS: Participants were largely of white European origin and resident in the South West of England. We examined the associations of maternal 25(OH)D concentrations in pregnancy with the following outcomes in the offspring: wheeze, asthma, atopy, eczema, hayfever, at mean age 7.5 years (n = 3652-4696 depending on outcome), IgE at 7 years (n = 2915) and lung function and bronchial responsiveness at mean age 8.7 years (n = 3728-3784).
RESULTS: Sixty-eight per cent of mothers had sufficient (> 50 nmol/L) concentrations of 25(OH)D, 27% were insufficient (27.5-49.99 nmol/L) and 5% were deficient (< 27.5 nmol/L). There was no evidence to suggest that maternal 25(OH)D concentration in pregnancy was associated with any respiratory or atopic outcome in the offspring. These findings remained after adjustment for season of measurement and for potential confounders. There was also no evidence that these relationships followed a non-linear form and no evidence that either deficient or high concentrations of maternal 25(OH)D were associated with atopic or respiratory outcomes.
CONCLUSIONS: We found no evidence that maternal blood 25(OH)D concentration in pregnancy is associated with childhood atopic or respiratory outcomes.

PMID: 24074336 [PubMed - in process]

Basophils and allergic inflammation.

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Basophils and allergic inflammation.

J Allergy Clin Immunol. 2013 Oct;132(4):789-801

Authors: Siracusa MC, Kim BS, Spergel JM, Artis D

Abstract
Basophils were discovered by Paul Ehrlich in 1879 and represent the least abundant granulocyte population in mammals. The relative rarity of basophils and their phenotypic similarities with mast cells resulted in this cell lineage being historically overlooked, both clinically and experimentally. However, recent studies in human subjects and murine systems have shown that basophils perform nonredundant effector functions and significantly contribute to the development and progression of TH2 cytokine-mediated inflammation. Although the potential functions of murine and human basophils have provoked some controversy, recent genetic approaches indicate that basophils can migrate into lymphoid tissues and, in some circumstances, cooperate with other immune cells to promote optimal TH2 cytokine responses in vivo. This article provides a brief historical perspective on basophil-related research and discusses recent studies that have identified previously unappreciated molecules and pathways that regulate basophil development, activation, and function in the context of allergic inflammation. Furthermore, we highlight the unique effector functions of basophils and discuss their contributions to the development and pathogenesis of allergic inflammation in human disease. Finally, we discuss the therapeutic potential of targeting basophils in preventing or alleviating the development and progression of allergic inflammation.

PMID: 24075190 [PubMed - in process]

Measures of gene expression in sputum cells can identify TH2-high and TH2-low subtypes of asthma.

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Measures of gene expression in sputum cells can identify TH2-high and TH2-low subtypes of asthma.

J Allergy Clin Immunol. 2013 Sep 24;

Authors: Peters MC, Mekonnen ZK, Yuan S, Bhakta NR, Woodruff PG, Fahy JV

Abstract
BACKGROUND: The 3-gene signature of periostin, chloride channel accessory 1 (CLCA1), and Serpin β2 (SERPINB2) in airway epithelial brushings is used to classify asthma into TH2-high and TH2-low endotypes. Little is known about the utility of gene profiling in sputum as a molecular phenotyping method.
OBJECTIVE: We sought to determine whether gene profiling in sputum cells can identify TH2-high and TH2-low subtypes of asthma.
METHODS: In induced sputum cell pellets from 37 asthmatic patients and 15 healthy control subjects, PCR was used to profile gene expression of the epithelial cell signature of IL-13 activation (periostin, CLCA1, and SERPINB2), TH2 genes (IL4, IL5, and IL13), and other genes associated with airway TH2 inflammation.
RESULTS: Gene expression levels of CLCA1 and periostin, but not SerpinB2, were significantly higher than normal in sputum cells from asthmatic subjects. Expression levels of IL-4, IL-5, and IL-13 were also significantly increased in asthmatic patients and highly correlated within individual subjects. By combining the expression levels of IL-4, IL-5, and IL-13 in a single quantitative metric ("TH2 gene mean"), 26 (70%) of the 37 asthmatic patients had TH2-high asthma, which was characterized by more severe measures of asthma and increased blood and sputum eosinophilia. TH2 gene mean values tended to be stable when initial values were very high or very low but fluctuated above or below the TH2-high cutoff when initial values were intermediate.
CONCLUSION: IL-4, IL-5, and IL-13 transcripts are easily detected in sputum cells from asthmatic patients, and their expression levels can be used to classify asthma into TH2-high and TH2-low endotypes.

PMID: 24075231 [PubMed - as supplied by publisher]

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