To determine the relationship of poor asthma control to bronchodilator response (BDR) phenotypes in children with normal spirometry.

STUDY DESIGN: Children with asthma were assessed for clinical indexes of poorly controlled asthma. Pre- and post-bronchodilator spirometry were performed, and the percent BDR was determined. Multivariate logistic regression assessed the relationship of the clinical indices to BDR at ≥8%, ≥10%, and ≥12% BDR thresholds.

RESULTS: There were 510 controller naïve children and 169 on controller medication. In the controller naïve population the mean age (±1 standard deviation) was 9.5 (3.4); 57.1% were male, 85.7% Hispanic. Demographics were similar in both populations. In the adjusted profile, significant clinical relationships were found particularly to positive BDR phenotypes ≥10% and ≥12% versus negative responses including younger age, (OR 2.0, 2.5; P < .05), atopy (OR 1.9, 2.6; P < .01), nocturnal symptoms in females (OR 3.4, 3.8; P < .01); β(2) agonist use (OR 1.7, 2.8; P < .01); and exercise limitation (OR 2.2, 2.5; P < .01) only in the controller naïve population.

CONCLUSIONS: The BDR phenotype ≥10% is significantly related to poor asthma control, providing a potentially useful objective tool in controller naïve children even when the pre-bronchodilator spirometry result is normal.

Inflammatory phenotypes are recognised in stable adult asthma, but are less established in childhood and acute asthma. Additionally, Chlamydophyla pneumoniae infection as a cause of noneosinophilic asthma is controversial.

This study examined the prevalence of inflammatory phenotypes and the presence of current Chlamydophyla pneumoniae infection in adults and children with stable and acute asthma. Adults with stable(n=29) or acute(n=22) asthma, healthy adults(n=11), and children with stable(n=49) or acute(n=28) asthma and healthy children(n=9) underwent clinical assessment and sputum induction. Sputum was assessed for inflammatory cells, and DNA was extracted from sputum cell suspensions and supernatant for Chlamydophyla pneumoniae detection using real-time PCR. Asthma phenotype was predominantly eosinophilic in children with acute asthma (50%) but neutrophilic in adults with acute asthma (82%). Paucigranulocytic asthma was the most common phenotype in both adults and children with stable asthma. Chlamydophyla pneumoniae was not detected in 99% of samples.

The pattern of inflammatory phenotypes differs between adults and children, with eosinophilic inflammation being more prevalent in both acute and stable childhood asthma, and neutrophilic inflammation being the dominant pattern of acute asthma in adults. The aetiology of neutrophilic asthma is unknown and is not explained by the presence of current active Chlamydophyla pneumoniae infection.

To systematically review and meta-analyse longitudinal studies on antibiotic use and subsequent development of wheeze and/or asthma in the light of study quality, outcome measurement, reverse causation (wheezing or asthmatic symptoms themselves have caused the prescription of antibiotics) and confounding-by- indication (respiratory tract infections that lead to antibiotic use may be the underlying cause triggering later development of asthma symptoms). Studies were identified through Pubmed, Medline and Embase searches up to November 1st 2010 and by perusing reference lists. Only English-language papers and studies with a longitudinal observational design were included. Study quality was assessed using the Newcastle-Ottawa scale.

We identified 21 longitudinal studies. The effect of antibiotic use on wheeze/asthma risk varied between studies. Eighteen studies were eligible for meta-analysis, showing a pooled odds ratio of 1.27 (95% confidence interval 1.12-1.43) for wheeze/asthma. When we eliminated studies with possible reverse causation and confounding-by-indication, the pooled risk estimate in the nine remaining studies was attenuated to an odds ratio of 1.12 (0.98-1.26). Definition of wheeze or asthma and age at follow-up differed widely between studies. Three studies focussed on wheeze/asthma beyond the age of 5-6 years with the presence of active symptoms and/or medication showing a pooled odds ratio of 1.08 (0.93-1.23) which was dominated by one large study.

Heterogeneity of disease definition, reverse causation and confounding-by-indication lead to overestimation of the association between antibiotic use and the subsequent development of wheeze/asthma. The association was weak when fully adjusted for these types of bias.

Epidemiological studies support the importance of adequate vitamin D status for the maintenance of pulmonary health and function; low levels of serum 25-hydroxyvitamin D ₃ are associated with an increased incidence or poor control of asthma, respiratory infection and chronic obstructive pulmonary disease (COPD). 1–4 Vitamin D is proposed to support respiratory health through promoting antimicrobial functions necessary for efficient clearance of pathogens, and dampening inflammation with the potential to damage lung structure and impair gaseous exchange. 4 However, the role of its major carrier protein, vitamin D-binding protein (VDBP), is less well understood. A paper by Wood et al in Thorax 5 together with independent studies, highlight the potential of VDBP to influence respiratory function both by determining vitamin D bioavailability and via direct effects on innate cell function.

VDBP is a glycosylated α-globulin protein synthesised by many tissues including the liver, kidneys, gonads and fat, and also by neutrophils. It binds circulating 25(OH)-vitamin D and 1,25(OH) ₂-vitamin D with high affinity. The levels of this protein far exceed circulating levels of these vitamin D metabolites, although VDBP has a rapid turnover rate. VDBP has three distinct domains which confer additional functions beyond carriage of vitamin D (reviewed by Chishimba et al 6). These functions include augmentation of the monocyte and neutrophil chemotactic response to the complement anaphylotoxin C5a, 7 8 scavenging of actin molecules released from necrotic cells 9 and, of interest to the current article, formation of a dimeric molecule with macrophage activating factor (DBP-MAF) which drives macrophages towards a more phagocytic phenotype with increased superoxide generation. 10 These activities of VDBP may be of …