Mechanisms of glucocorticoid action and insensitivity in airways disease.

Pulm Pharmacol Ther. 2014 Sep 9;

Authors: Boardman C, Chachi L, Gavrila A, Keenan CR, Perry MM, Xia YC, Meurs H, Sharma P

Abstract
Glucocorticoids are the mainstay for the treatment of chronic inflammatory diseases including asthma and chronic obstructive pulmonary disease (COPD). However, it has been recognized that glucocorticoids do not work well in certain patient populations suggesting reduced sensitivity. The ultimate biologic responses to glucocorticoids are determined by not only the concentration of glucocorticoids but also the differences between individuals in glucocorticoid sensitivity, which is influenced by multiple factors. Studies are emerging to understand these mechanisms in detail, which would help in increasing glucocorticoid sensitivity in patients with chronic airways disease. This review aims to highlight both classical and emerging concepts of the anti-inflammatory mechanisms of glucocorticoids and also review some novel strategies to overcome steroid insensitivity in airways disease.

PMID: 25218650 [PubMed - as supplied by publisher]

Air pollution, avoidance behaviour and children's respiratory health: Evidence from England.

J Health Econ. 2014 Aug 4;

Authors: Janke K

Abstract
Despite progress in air pollution control, concerns remain over the health impact of poor air quality. Governments increasingly issue air quality information to enable vulnerable groups to avoid exposure. Avoidance behaviour potentially biases estimates of the health effects of air pollutants. But avoidance behaviour imposes a cost on individuals and therefore may not be taken in all circumstances. This paper exploits panel data at the English local authority level to estimate the relationship between children's daily hospital emergency admissions for respiratory diseases and common air pollutants, while allowing for avoidance behaviour in response to air pollution warnings. A 1% increase in nitrogen dioxide or ozone concentrations increases hospital admissions by 0.1%. For the subset of asthma admissions - where avoidance is less costly - there is evidence of avoidance behaviour. Ignoring avoidance behaviour, however, does not result in statistically significant underestimation of the health effect of air pollution.

PMID: 25220266 [PubMed - as supplied by publisher]

Early risk factors for pubertal asthma.

Clin Exp Allergy. 2014 Sep 14;

Authors: Hovland V, Riiser A, Mowinckel P, Carlsen KH, Carlsen KC

Abstract
BACKGROUND: Early life risk factors are previously described for childhood asthma, but less is known related to asthma in adolescence. We aimed to investigate early risk factors (before two years) for pubertal asthma and secondarily for pubertal asthma phenotypes based upon allergic comorbidities.
METHODS: Based on data from 550 adolescents in the prospective birth cohort "Environment and Childhood Asthma" study, subjects were categorized by recurrent bronchial obstruction (rBO) 0-2 years, asthma 2-10 years and pubertal asthma from 10-16 years including incident asthma in puberty and asthma in remission from 10 to 16 years or as never rBO/asthma 0-16 years. Asthma in puberty was further classified based on the comorbidities atopic dermatitis and allergic rhinitis from 10-16 years. Twenty-three common asthma risk factors identified by two years of age, including frequency and persistence of bronchial obstruction (severity score), were analysed by weighted logistic regression for each phenotype.
RESULTS: In adjusted models the risk of pubertal asthma increased significantly with higher severity score, parental rhinitis, being the first born child and familial stress around birth. Pubertal asthma in remisssion was significantly associated with severity score and number of lower respiratory tract infections and inversely associated with breastfeeding beyond four months. Pubertal incident asthma was more common among first born children. All asthma phenotypes with allergic diseases were significantly associated with severity score whereas familial perinatal stress increased the risk of asthma only. Asthma combined with allergic rhinitis was associated with parental asthma and being first born, whereas the risk of asthma with both atopic dermatitis and allergic rhinitis increased with higher paternal education, atopic dermatitis, being first born and familial perinatal stress .
CONCLUSION AND CLINICAL RELEVANCE: Important early risk factor for pubertal asthma were early airways obstruction, parental rhinitis, being the first born child and perinatal familial stress. This article is protected by copyright. All rights reserved.

PMID: 25220447 [PubMed - as supplied by publisher]

The association between paracetamol use and asthma: causation or coincidence?

Clin Exp Allergy. 2014 Sep 14;

Authors: Weatherall M, Ioannides S, Braithwaite I, Beasley R

Abstract
A better understanding of the causation of asthma and allergic disorders could potentially lead to intervention strategies that reduce their prevalence and severity. One potential causative factor is the use of paracetamol. Most of the evidence for the link with asthma is from non-experimental studies of paracetamol exposure in utero, infancy, childhood and adult life, however it has been difficult to rule out confounding and bias in the associations observed. The two randomised clinical trials of the effect of paracetamol in patients with asthma have been difficult to interpret, due to methodological issues. There have been no randomised controlled trials of paracetamol use and the development of asthma. Both asthma and paracetamol use are common, and so even if there is a relatively small effect of paracetamol exposure on the development of asthma or its severity, then such an effect would be of major public health significance. It is proposed that randomised controlled trials of the effect of paracetamol on the development of asthma and its severity are a high research priority. This article is protected by copyright. All rights reserved.

PMID: 25220564 [PubMed - as supplied by publisher]