LTA4H rs2660845 association with montelukast response in early and late-onset asthma.

Leukotrienes play a central pathophysiological role in both paediatric and adult asthma. However, 35% to 78% of asthmatics do not respond to leukotriene inhibitors. In this study we tested the role of the LTA4H regulatory variant rs2660845 and age of asthma onset in response to montelukast in ethnically diverse populations. We identified and genotyped 3,594 asthma patients treated with montelukast (2,514 late-onset and 1,080 early-onset) from seven cohorts (UKBiobank, GoSHARE, BREATHE, Tayside RCT, PAGES, GALA II and SAGE). Individuals under montelukast treatment experiencing at least one exacerbation in a 12-month period were compared against individuals with no exacerbation, using logistic regression for each cohort and meta-analysis. While no significant association was found with European late-onset subjects, a meta-analysis of 523 early-onset individuals from European ancestry demonstrated the odds of experiencing asthma exacerbations by carriers of at least one G allele, despite montelukast treatment, were increased (odds-ratio = 2.92, 95%confidence interval (CI): 1.04-8.18, I2 = 62%, p = 0.0412) compared to those in the AA group. When meta-analysing with other ethnic groups, no significant increased risk of asthma exacerbations was found (OR = 1.60, 95% CI: 0.61-4.19, I2 = 85%, p = 0.342). Our study demonstrates that genetic variation in LTA4H, together with timing of asthma onset, may contribute to variability in montelukast response. European individuals with early-onset (≤18y) carrying at least one copy of rs2660845 have increased odd of exacerbation under montelukast treatment, presumably due to the up-regulation of LTA4H activity. These findings support a precision medicine approach for the treatment of asthma with montelukast.

Impact of a bronchiolitis clinical care pathway on treatment and hospital stay.

UNLABELLED: Bronchiolitis is a common lower respiratory tract infection of infancy where management has varied considerably in the past. The aim of the present study was to determine whether patient treatment and outcomes changed after introduction of a clinical care pathway. Infants aged up to 6 months admitted to hospital with bronchiolitis were identified as part of an annual audit of bronchiolitis management between winters 2003/2004 and 2009/2010. The primary outcome, duration of stay (DOS), was compared before and after the clinical pathway was introduced before the winter 2005/2006. There were 328 infants identified, mean age 75 days, respiratory syncitial virus was detected in 89%. After the clinical pathway was introduced, the proportion of infants prescribed salbutamol fell from 50% to 8% (p < 0.001) and ipratropium bromide from 38% to 0% (p < 0.001) but the proportion prescribed antibiotics was unchanged. The median DOS was 79 h prior to the clinical pathway and 66 h afterwards (p = 0.010) but there was no difference in days where supplemental oxygen or nasogastric feeding was required. CONCLUSIONS: A clinical pathway for the management of acute bronchiolitis can be implemented in the hospital setting and the conservative approach, in particular not prescribing bronchodilators, is not associated with prolonged duration of stay.