Changes In Airway Hyperresponsiveness Research Articles

Nanoparticle-Induced Airway Eosinophilia Is Independent of ILC2 Signaling but Associated With Sex Differences in Macrophage Phenotype Development.

The majority of lung diseases occur with a sex bias in terms of prevalence and/or severity. Previous studies demonstrated that, compared with males, female mice develop greater eosinophilic inflammation in the airways after multiwalled carbon nanotube (MWCNT) exposure. However, the mechanism by which this sex bias occurs is unknown. Two immune cells that could account for the sex bias are type II innate lymphoid cells (ILC2s) and alveolar macrophages (AMs). In order to determine which immune cell type was responsible for MWCNT-induced airway eosinophil recruitment and subsequent sex differences in inflammation and disease, male and female C57BL/6 mice were exposed to MWCNTs (2 mg/kg) via oropharyngeal aspiration, and the respiratory immune response was assessed 7 d later. Greater eosinophilia and eotaxin 2 levels were observed in MWCNT-treated females and corresponded with greater changes in airway hyperresponsiveness than those in MWCNT-treated males. In MWCNT-treated females, there was a significant increase in the frequency of ILC2s within the lungs compared with control animals. However, depletion of ILC2s via α-CD90.2 administration did not decrease eosinophil recruitment 24 h and 7 d after MWCNT exposure. AMs isolated from control and MWCNT-treated animals demonstrated that M2a macrophage phenotype gene expression, ex vivo cytokine production, and activation of (p)STAT6 were upregulated to a significantly greater degree in MWCNT-treated females than in males. Our findings suggest that sex differences in AM phenotype development, not ILC2 signaling, are responsible for the observed female bias in eosinophilic inflammation after MWCNT inhalation.

The effect of tezepelumab on airway hyperresponsiveness to mannitol in asthma (UPSTREAM).

Thymic stromal lymphopoietin (TSLP), an epithelial upstream cytokine, initiates production of type-2 (T2) cytokines with eosinophilia and possibly airway hyperresponsiveness (AHR) in asthma.This study aimed to determine whether tezepelumab (a human monoclonal antibody targeting TSLP) decreases AHR and airway inflammation in patients with symptomatic asthma on maintenance treatment with inhaled corticosteroids. In this double-blind, placebo-controlled randomised trial adult patients with asthma and AHR to mannitol received either 700 mg tezepelumab or placebo intravenously at 4-week intervals for 12 weeks. AHR to mannitol was assessed, and a bronchoscopy was performed at baseline and after 12 weeks. The primary outcome was the change in AHR from baseline to week-12 and secondary outcomes were changes in airway inflammation. Forty patients were randomised to receive either tezepelumab (n=20) or placebo (n=20). The mean change in PD15 with tezepelumab was 1.9 DD (95% CI 1.2 to 2.5) versus 1·0 (95% CI 0.3 to 1.6) with placebo; p=0.06. Nine (45%) tezepelumab and three (16%) placebo patients had a negative PD15 test at week-12, p=0.04. Airway tissue and BAL eosinophils decreased by 74% (95% CI -53 to -86) and 75% (95% CI -53 to -86) respectively with tezepelumab compared with an increase of 28% (95% CI -39 to 270) and a decrease of 7% (95% CI -49 to 72) respectively with placebo, p=0.004 and p=0.01. Inhibiting TSLP-signalling with tezepelumab reduced the proportion of patients with AHR and decreased eosinophilic inflammation in BAL and airway tissue.

Androgen receptor activation alleviates airway hyperresponsiveness, inflammation, and remodeling in a murine model of asthma

Epidemiological studies demonstrate an apparent sex-based difference in the prevalence of asthma, with a higher risk in boys than girls, which is reversed postpuberty, where women become more prone to asthma than men, suggesting a plausible beneficial role for male hormones, especially androgens as a regulator of pathophysiology in asthmatic lungs. Using a murine model of asthma developed with mixed allergen (MA) challenge, we report a significant change in airway hyperresponsiveness (AHR), as demonstrated by increased thickness of epithelial and airway smooth muscle layers and collagen deposition, as well as Th2/Th17-biased inflammation in the airways of non-gonadectomized (non-GDX) and gonadectomized (GDX) male mice. Here, compared with non-GDX mice, MA-induced AHR and inflammatory changes were more prominent in GDX mice. Activation of androgen receptor (AR) using 5α-dihydrotestosterone (5α-DHT, AR agonist) resulted in decreased Th2/Th17 inflammation and remodeling-associated changes, resulting in improved lung function compared with MA alone challenged mice, especially in GDX mice. These changes were not observed with Flutamide (Flut, AR antagonist). Overall, we show that AR exerts a significant and beneficial role in asthma by regulating AHR and inflammation.

Factors associated with longitudinal changes in airway hyperresponsiveness: the Vlagtwedde-Vlaardingen study

Factors associated with longitudinal changes in airway hyperresponsiveness: the Vlagtwedde-Vlaardingen study

Roles of Bronchopulmonary C-fibers in airway Hyperresponsiveness and airway remodeling induced by house dust mite

BackgroundAsthma is characterized by chronic airway inflammation, airway hyperresponsiveness (AHR), and airway remodeling. While exposure of house dust mites (HDM) is a common cause of asthma, the pathogenesis of the HDM-induced asthma is not fully understood. Bronchopulmonary C-fibers (PCFs) contribute to the neurogenic inflammation, viral infection induced-persistent AHR, and ovalbumin induced collagen deposition largely via releasing neuropeptides, such as substance P (SP). However, PCF roles in the pathogenesis of the HDM-induced asthma remain unexplored. The goal of this study was to determine what role PCFs played in generating these characteristics.MethodsWe compared the following variables among the PCF-intact and -degenerated BALB/c mice with and without chronic HDM exposure (four groups): 1) AHR and pulmonary SP; 2) airway smooth muscle (ASM) mass; 3) pulmonary inflammatory cells; and 4) epithelium thickening and mucus secretion.ResultsWe found that HDM evoked AHR associated with upregulation of pulmonary SP and inflammation, ASM mass increase, epithelium thickenings, and mucus hypersecretion. PCF degeneration decreased the HDM-induced changes in AHR, pulmonary SP and inflammation, and ASM mass, but failed to significantly affect the epithelium thickening and mucus hypersecretion.ConclusionOur data suggest an involvement of PCFs in the mechanisms by which HDM induces allergic asthma via airway inflammation, AHR, and airway remodeling.

KIT Inhibition by Imatinib in Patients with Severe Refractory Asthma

BackgroundMast cells are present in the airways of patients who have severe asthma despite glucocorticoid treatment; these cells are associated with disease characteristics including poor quality of life and inadequate asthma control. Stem cell factor and its receptor, KIT, are central to mast-cell homeostasis. We conducted a proof-of-principle trial to evaluate the effect of imatinib, a KIT inhibitor, on airway hyperresponsiveness, a physiological marker of severe asthma, as well as on airway mast-cell numbers and activation in patients with severe asthma.MethodsWe conducted a randomized, double-blind, placebo-controlled, 24-week trial of imatinib in patients with poorly controlled severe asthma who had airway hyperresponsiveness despite receiving maximal medical therapy. The primary end point was the change in airway hyperresponsiveness, measured as the concentration of methacholine required to decrease the forced expiratory volume in 1 second by 20% (PC20). Patients also underwent bronchoscopy.ResultsAmong the 62 patients who underwent randomization, imatinib treatment reduced airway hyperresponsiveness to a greater extent than did placebo. At 6 months, the methacholine PC20 increased by a mean (±SD) of 1.73±0.60 doubling doses in the imatinib group, as compared with 1.07±0.60 doubling doses in the placebo group (P=0.048). Imatinib also reduced levels of serum tryptase, a marker of mast-cell activation, to a greater extent than did placebo (decrease of 2.02±2.32 vs. 0.56±1.39 ng per milliliter, P=0.02). Airway mast-cell counts declined in both groups. Muscle cramps and hypophosphatemia were more common in the imatinib group than in the placebo group.ConclusionsIn patients with severe asthma, imatinib decreased airway hyperresponsiveness, mast-cell counts, and tryptase release. These results suggest that KIT-dependent processes and mast cells contribute to the pathobiologic basis of severe asthma. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01097694.)

Features of the bronchial bacterial microbiome associated with atopy, asthma, and responsiveness to inhaled corticosteroid treatment

Compositional differences in the bronchial bacterial microbiota have been associated with asthma, but it remains unclear whether the findings are attributable to asthma, to aeroallergen sensitization, or to inhaled corticosteroid treatment. We sought to compare the bronchial bacterial microbiota in adults with steroid-naive atopic asthma, subjects with atopy but no asthma, and nonatopic healthy control subjects and to determine relationships of the bronchial microbiota to phenotypic features of asthma. Bacterial communities in protected bronchial brushings from 42 atopic asthmatic subjects, 21 subjects with atopy but no asthma, and 21 healthy control subjects were profiled by using 16S rRNA gene sequencing. Bacterial composition and community-level functions inferred from sequence profiles were analyzed for between-group differences. Associations with clinical and inflammatory variables were examined, including markers of type 2-related inflammation and change in airway hyperresponsiveness after 6weeks of fluticasone treatment. The bronchial microbiome differed significantly among the 3 groups. Asthmatic subjects were uniquely enriched in members of the Haemophilus, Neisseria, Fusobacterium, and Porphyromonas species and the Sphingomonodaceae family and depleted in members of the Mogibacteriaceae family and Lactobacillales order. Asthma-associated differences in predicted bacterial functions included involvement of amino acid and short-chain fatty acid metabolism pathways. Subjects with type 2-high asthma harbored significantly lower bronchial bacterial burden. Distinct changes in specific microbiota members were seen after fluticasone treatment. Steroid responsiveness was linked to differences in baseline compositional and functional features of the bacterial microbiome. Even in subjects with mild steroid-naive asthma, differences in the bronchial microbiome are associated with immunologic and clinical features of the disease. The specific differences identified suggest possible microbiome targets for future approaches to asthma treatment or prevention.

Acute respiratory changes and pulmonary inflammation involving a pathway of TGF-β1 induction in a rat model of chlorine-induced lung injury

We investigated acute and delayed respiratory changes after inhalation exposure to chlorine (Cl2) with the aim to understand the pathogenesis of the long-term sequelae of Cl2-induced lung-injury.In a rat model of nose-only exposure we analyzed changes in airway hyperresponsiveness (AHR), inflammatory responses in airways, expression of pro-inflammatory markers and development of lung fibrosis during a time-course from 5h up to 90days after a single inhalation of Cl2. A single dose of dexamethasone (10mg/kg) was administered 1h following Cl2-exposure.A 15-min inhalation of 200ppm Cl2 was non-lethal in Sprague-Dawley rats. At 24h post exposure, Cl2-exposed rats displayed elevated numbers of leukocytes with an increase of neutrophils and eosinophils in bronchoalveolar lavage (BAL) and edema was shown both in lung tissue and the heart. At 24h, the inflammasome-associated cytokines IL-1β and IL-18 were detected in BAL. Concomitant with the acute inflammation a significant AHR was detected. At the later time-points, a delayed inflammatory response was observed together with signs of lung fibrosis as indicated by increased pulmonary macrophages, elevated TGF-β expression in BAL and collagen deposition around airways. Dexamethasone reduced the numbers of neutrophils in BAL at 24h but did not influence the AHR.Inhalation of Cl2 in rats leads to acute respiratory and cardiac changes as well as pulmonary inflammation involving induction of TGF-β1. The acute inflammatory response was followed by sustained macrophage response and lack of tissue repair. It was also found that pathways apart from the acute inflammatory response contribute to the Cl2-induced respiratory dysfunction.

Double-stranded RNA evokes exacerbation in a mouse model of corticosteroid refractory asthma.

RNA viruses are a major cause of respiratory infections and are known to exacerbate asthma and other respiratory diseases. Our aim was to test the ability of poly(I:C) (polyinosinic:polycytidylic acid), a viral surrogate, to elicit exacerbation in a model of severe asthma driven by HDM (house dust mite) in FCA (Freund's complete adjuvant). Poly(I:C) was administered intranasally around the HDM challenge in FCA-HDM-sensitized animals. Changes in AHR (airway hyperresponsiveness), BALF (bronchoalveolar lavage fluid) inflammatory infiltrate, HDM-specific immunoglobulins and cytokine/chemokine release were evaluated at different points after the challenge. The effect of oral dexamethasone was also assessed. Exacerbation was achieved when poly(I:C) was administered 24 h before the HDM challenge and was characterized by enhanced AHR and an increase in the numbers of neutrophils, macrophages and lymphocytes in the BALF. Th1, Th2 and Th17 cytokines were also elevated at different time points after the challenge. Peribronchial and alveolar inflammation in lung tissue were also augmented. AHR and inflammatory infiltration showed reduced sensitivity to dexamethasone treatment. We have set up a model that mimics key aspects of viral exacerbation in a corticosteroid-refractory asthmatic phenotype which could be used to evaluate new therapies for this condition.

Effects of Weight Loss on Airway Responsiveness in Obese Adults With Asthma: Does Weight Loss Lead to Reversibility of Asthma?

The growing epidemics of obesity and asthma are major public health concerns. Although asthma-obesity links are widely studied, the effects of weight loss on asthma severity measured by airway hyperresponsiveness (AHR) have received limited attention. The main study objective was to examine whether weight reduction reduces asthma severity in obese adults with asthma. In a prospective, controlled, parallel-group study, we followed 22 obese participants with asthma aged 18 to 75 years with a BMI ≥ 32.5 kg/m2 and AHR (provocative concentration of methacholine causing a 20% fall in FEV1 [PC20] < 16 mg/mL). Sixteen participants followed a behavioral weight reduction program for 3 months, and six served as control subjects. The primary outcome was change in AHR over 3 months. Changes in lung function, asthma control, and quality of life were secondary outcomes. At study entry, participant mean ± SD age was 44 ± 9 years, 95% were women, and mean BMI was 45.7 ± 9.2 kg/m2. After 3 months, mean weight loss was 16.5 ± 9.9 kg in the intervention group, and the control group had a mean weight gain of 0.6 ± 2.6 kg. There were significant improvements in PC20 (P = .009), FEV1 (P = .009), FVC (P = .010), asthma control (P < .001), and asthma quality of life (P = .003) in the intervention group, but these parameters remained unchanged in the control group. Physical activity levels also increased significantly in the intervention group but not in the control group. Weight loss in obese adults with asthma can improve asthma severity, AHR, asthma control, lung function, and quality of life. These findings support the need to actively pursue healthy weight-loss measures in this population.

Inflammatory Mediators in Induced Sputum and Airway Hyperresponsiveness in Cough Variant Asthma during Long-Term Inhaled Corticosteroid Treatment

Objective. This study aimed to investigate improvements in inflammatory mediator levels in induced sputum and airway hyperresponsiveness (AHR) in cough variant asthma (CVA) during long-term inhaled corticosteroid (ICS) treatment. Patients and Methods. Patients with CVA (N = 35) and classic asthma (N = 26) and healthy subjects (N = 24) were recruited into this study. All patients were treated with budesonide (400 μg/day). Measurement of inflammatory mediators in induced sputum and PD20-FEV1 (the accumulated provocative dose resulting in a 20% decrease in FEV1) in histamine-challenged subjects was performed every three months after the start of medication. Interleukin- (IL-) 5 and IL-10 were assayed by ELISA, and the percentage of eosinophils was detected with Giemsa stain. Trends during the follow-up period were analyzed using a general linear model. Results. Inflammatory mediator levels in induced sputum and PD20-FEV1 in patients with CVA and classic asthma differed from those in the control group, although no differences were found in the two asthmatic groups. PD20-FEV1 significantly increased in CVA patients after ICS treatment for 3 months, while classic asthma patients exhibited a delayed change in AHR. After ICS treatment, levels of IL-5 and IL-10 as well as the percentage of eosinophils in the CVA group were altered at 3 months and 6 months, respectively. Accordingly, the level of inflammatory mediators in classic asthma changed more slowly. Conclusion. CVA has a greater improvement in airway inflammation and airway hyperresponsiveness (AHR) than classic asthma with respect to inhaled corticosteroid (ICS). Short-term ICS considerably reduces AHR although longer treatment is required for complete control of airway inflammation.

Airway Responsiveness Measured by Forced Oscillation Technique in Severely Obese Patients, before and after Bariatric Surgery

Background. The influence of obesity on airway responsiveness remains controversial. Objective. This study was designed to investigate airway responsiveness, airway inflammation, and the influence of sleep apnea syndrome (SAS), in severely obese subjects, before and after bariatric surgery. Methods. A total of 120 non-asthmatic obese patients were referred consecutively for pre-bariatric surgery evaluation. Lung function, airway responsiveness to methacholine, exhaled nitric oxide measurement, and sleep studies were performed. Airway hyperresponsiveness (AHR) was defined as a 50% or greater increase in respiratory resistance measured using the forced oscillation technique in response to a methacholine dose ≤2000 μg. Forced expiratory volume in 1 second (FEV1) was measured after the last methacholine dose. Airway responsiveness was reevaluated after weight loss in patients with a pre-surgery AHR. Results. AHR was found in 16 patients. The percent FEV1 decrease or percent respiratory resistance increase in response to methacholine was related to baseline expiratory airflow (forced expiratory flow at 50%) (r = 0.26, p < .006 and r = 0.315, p = .0005, respectively) but not to body mass index (BMI) or exhaled nitric oxide. Both airway responsiveness parameters were significantly related to forced expiratory flow at 25–75%/forced vital capacity, a measure of airway size relative to lung size (r = 0.27, p < .005 and r = 0.25, p < .007, respectively). Sleep apnea was not significantly associated with AHR or airway inflammation. About 11 patients with AHR were reevaluated 18 months to 2 years after surgery, with no change in AHR associated with weight loss. Conclusion. Airway responsiveness is not related to BMI or to SAS. AHR in severely obese patients might be related to distal airway obstruction or low relative airway size.

Update in Pulmonary and Critical Care Medicine

This Update in Pulmonary and Critical Care Medicine features 12 articles published in 2009. Topics include chronic obstructive pulmonary disease, asthma, pneumonia, glucose control and mortality, e...

Changes in the prevalence of asthma in adults since 1966: the Busselton health study

Asthma prevalence has increased worldwide; although less so in developed countries recently. This study assessed changes in the prevalence of asthma and related symptoms in the Busselton community since 1966. Cross-sectional respiratory health surveys of Busselton adults were conducted in 1966, 1969, 1972, 1975, 1981, 1990 and 2005-2007. Logistic regression models were used to estimate prevalence rates of asthma, respiratory symptoms, smoking, airway hyperresponsiveness (AHR) and atopy and to make comparisons in 2005-2007 and previous survey years. Asthma was defined as ever having doctor-diagnosed asthma (DDA). The prevalence of DDA was around 6% from 1966 to 1975, 8% in 1981 and rose to 19% in 2005-2007. From 1981 to 2005-2007, smoking prevalence declined and obesity and atopy increased but changes in these variables explained only a small part of the increase in DDA. Wheeze and cough/phlegm increased but AHR, breathlessness and doctor-diagnosed bronchitis remained relatively stable over the same period. These observations indicate that the increase in DDA is partly explained by increased symptoms and atopy. The lack of changes in AHR and doctor-diagnosed bronchitis suggests that factors such as diagnostic transfer and increased awareness of asthma have also contributed to the rise in prevalence of DDA.

Repeated Bouts of Moderate-Intensity Aerobic Exercise Reduce Airway Reactivity in a Murine Asthma Model

We have reported that moderate-intensity aerobic exercise training attenuates airway inflammation in mice sensitized/challenged with ovalbumin (OVA). The current study determined the effects of repeated bouts of aerobic exercise at a moderate intensity on airway hyperresponsiveness (AHR) in these mice. Mice were sensitized/challenged with OVA or saline and exercised at a moderate intensity 3 times/week for 4 weeks. At protocol completion, mice were analyzed for changes in AHR via mechanical ventilation. Results show that exercise decreased total lung resistance 60% in OVA-treated mice as compared with controls; exercise also decreased airway smooth muscle (ASM) thickness. In contrast, exercise increased circulating epinephrine levels 3-fold in saline- and OVA-treated mice. Because epinephrine binds beta(2)-adrenergic receptors (AR), which facilitate bronchodilatation, the role of beta(2)-AR in exercise-mediated improvements in AHR was examined. Application of the beta(2)-AR antagonist butoxamine HCl blocked the effects of exercise on lung resistance in OVA-treated mice. In parallel, ASM cells were examined for changes in the protein expression of beta(2)-AR and G-protein receptor kinase-2 (GRK-2); GRK-2 promotes beta(2)-AR desensitization. Exercise had no effect on beta(2)-AR expression in ASM cells of OVA-treated mice; however, exercise decreased GRK-2 expression by 50% as compared with controls. Exercise also decreased prostaglandin E(2) (PGE(2)) production 5-fold, but had no effect on E prostanoid-1 (EP1) receptor expression within the lungs of OVA-treated mice; both PGE(2) and the EP1 receptor have been implicated in beta(2)-AR desensitization. Together, these data indicate that moderate-intensity aerobic exercise training attenuates AHR via a mechanism that involves beta(2)-AR.

Effects of inhaled fluticasone propionate on CTLA‐4‐positive CD4+CD25+ cells in induced sputum in mild asthmatics

Cytotoxic T-lymphocyte antigen 4 (CTLA-4) signalling of regulatory T cells regulates mucosal lymphocyte tolerance and differentiation, and may therefore have a beneficial effect in allergic diseases such as asthma. The aim of this study was to evaluate the effects of fluticasone propionate (FP) on CD4+CD25+ T cell co-expression of CTLA-4 in the sputum of mild asthmatic subjects. Eleven mild, stable asthmatic subjects completed a double-blind, randomized, crossover, placebo-controlled study to compare the effects of 14 days 200 microg twice daily FP and placebo. Before and after treatment, airway hyperresponsiveness was measured, and sputum was induced for measurements of CTLA-4+CD4+CD25+ cells, eosinophils and levels of IL-10, IL-13 and transforming growth factor (TGF)-beta. FP treatment increased co-expression of CTLA-4 on sputum CD4+CD25+ cells from a mean (SEM) of 7.9% (1.8) to 12.7% (3.3) after 14 days treatment (P < 0.05) compared with placebo. FP treatment also significantly increased IL-10 levels, reduced per cent sputum eosinophils, and reduced airway hyperresponsiveness (P < 0.05). There was a significant negative correlation between the change in airway hyperresponsiveness and per cent sputum eosinophils (P < 0.01), but no correlation with changes in CTLA-4+CD4+CD25+ cells (P > 0.05). There was no change in the levels of sputum IL-13 or TGF-beta. The percentage of airway CTLA-4+CD4+CD25+ cells increased after FP treatment, coincident with improvements in airway inflammation and hyperresponsiveness.Whether improved asthma assessments are related to the increase in CTLA-4+CD4+CD25+ cells and thus improved regulation of T-cell tolerance and differentiation will require a larger sample size to determine. The normalization of CTLA-4+CD4+CD25+ cells in asthma may contribute to the management of this disease.

Murine Lung Responses to Ambient Particulate Matter: Genomic Analysis and Influence on Airway Hyperresponsiveness

BackgroundAsthma is a complex disease characterized by airway hyperresponsiveness (AHR) and chronic airway inflammation. Epidemiologic studies have demonstrated that exposures to environmental factors such as ambient particulate matter (PM), a major air pollutant, contribute to increased asthma prevalence and exacerbations.ObjectiveWe investigated pathophysiologic responses to Baltimore, Maryland, ambient PM (median diameter, 1.78 μm) in a murine model of asthma and attempted to identify PM-specific genomic/molecular signatures.MethodsWe exposed ovalbumin (OVA)-sensitized A/J mice intratracheally to PM (20 mg/kg), and assayed both AHR and bronchoalveolar lavage (BAL) on days 1, 4, and 7 after PM exposure. Lung gene expression profiling was analyzed in OVA- and PM-challenged mice.ResultsConsistent with this murine model of asthma, we observed significant increases in airway responsiveness in OVA-treated mice, with PM exposure inducing significant changes in AHR in both naive mice and OVA-induced asthmatic mice. PM evoked eosinophil and neutrophil infiltration into airways, elevated BAL protein content, and stimulated secretion of type 1 T helper (TH1) cytokines [interferon-γ, interleukin-6 (IL-6), tumor necrosis factor-α] and TH2 cytokines (IL-4, IL-5, eotaxin) into murine airways. Furthermore, PM consistently induced expression of genes involved in innate immune responses, chemotaxis, and complement system pathways.ConclusionThis study is consistent with emerging epidemiologic evidence and indicates that PM exposure evokes proinflammatory and allergic molecular signatures that may directly contribute to the asthma susceptibility in naive subjects and increased severity in affected asthmatics.

Implementation of an asthma guideline for the management of childhood asthma in general practice: a randomised controlled trial

The aim of the study was to assess, in a randomised, controlled design, the efficacy of different strategies to improve childhood asthma management. Three interventions directed to three groups of general practitioners were compared: Group A - dissemination of a guideline; Group B - guideline dissemination plus an educational session; Group C - guideline dissemination, educational session, plus individualised treatment advice based on airway hyperresponsiveness (AHR) and symptoms. Efficacy of the three strategies was assessed by evaluating change in AHR in 362 children after one year. The overall between-group effect of the severity of AHR was not significantly different (P=0.09). In Groups A and C an improvement was seen in nocturnal symptoms (P=0.02) and in Group C an improvement was seen in the prescription of inhaled corticosteroids (P=0.03). In this study, the combined implementation strategy did not show a clear improvement in the management of children with asthma in general practice.

Asthma and obesity in children

Childhood asthma and obesity are significant public health problems. The prevalence of both disorders has increased considerably in the past decade. This review will highlight recent publications regarding the nature of the relationship between asthma and obesity and the clinical effects of obesity in children with asthma. Most prospective studies suggest that obesity increases the risk of subsequent asthma. Possible mechanisms for the relationship between asthma and obesity include airway inflammation, mechanical changes associated with obesity, changes in airway hyper-responsiveness, and changes in physical activity and diet. Most studies suggest that obesity increases the clinical severity of asthma and decreases quality of life in children with asthma. More research is required to further define and clarify the relationship between asthma and obesity in children. There are many questions and few answers regarding the relationship between asthma and obesity in children. Additional studies are needed to clarify the relationship between the two epidemics so that effective interventions can be developed to improve the health and lives of children with both asthma and obesity.

Changes in airway hyperresponsiveness following smoking cessation: Comparisons between Mch and AMP

Given the observed association between smoking, inflammation and airway hyperresponsiveness (AHR) one may predict that smoking cessation may improve AHR. However, only a few studies have investigated the effect of smoking on AHR and their results appear to be conflicting depending on the stimulus used in their bronchoprovocation protocol. The aim of the current study was to compare changes in AHR between direct (methacholine (Mch)) and indirect (adenosine 5'monophosphate (AMP)) stimuli before and at different time points after smoking cessation in smokers with allergic rhinitis (+/-asthma). We have prospectively studied changes in AHR to inhaled Mch and AMP in smokers with allergic rhinitis (+/-asthma), before and at 6 and 12 months after smoking cessation. It was found that 28% (16/57) of the participants had quit smoking by the end of the study. No significant change in AHR was observed in smoking cessation failures. A significant improvement in AHR to AMP but not Mch was observed 6 months after smoking cessation in quitters; a 1.2 doubling concentrations change in PC20 AMP was measured whereas only a 0.4 doubling concentrations change was observed for PC20 Mch. However, after 12 months smoking cessation the improvement in AHR became significant for both AMP and Mch, their dose-response curves being displaced to the right to a similar extent (1.4 and 1.1 doubling concentrations for AMP and Mch, respectively). Smoking cessation can improve AHR in smokers who quit with a 6 months improvement being reported for the airways response to AMP but not Mch. AMP challenge may detect earlier changes in AHR in smokers during smoking cessation.