Kenneth R. Chapman

The association between chronic exposure to traffic-related air pollution and ischemic heart disease.

Increasing evidence links air pollution to the risk of cardiovascular disease. This study investigated the association between ischemic heart disease (IHD) prevalence and exposure to traffic-related air pollution (nitrogen dioxide [NO2], fine particulate matter [PM2.5], and ozone [O3]) in a population of susceptible subjects in Toronto. Local (NO2) exposures were modeled using land use regression based on extensive field monitoring. Regional exposures (PM2.5, O3) were modeled as confounders using inverse distance weighted interpolation based on government monitoring data. The study sample consisted of 2360 patients referred during 1992 to 1999 to a pulmonary clinic at the Toronto Western Hospital in Toronto, Ontario, Canada, to diagnose or manage a respiratory complaint. IHD status was determined by clinical database linkages (ICD-9-CM 412–414). The association between IHD and air pollutants was assessed with a modified Poisson regression resulting in relative risk estimates. Confounding was controlled with individual and neighborhood-level covariates. After adjusting for multiple covariates, NO2 was significantly associated with increased IHD risk, relative risk (RR) = 1.33 (95% confidence interval [CI]: 1.2, 1.47). Subjects living near major roads and highways had a trend toward an elevated risk of IHD, RR = 1.08 (95% CI: 0.99, 1.18). Regional PM2.5 and O3 were not associated with risk of IHD.

Pulmonary function in adolescents with mild idiopathic scoliosis.

Spirometric indices, lung volumes, maximum voluntary ventilation, and maximum inspiratory and expiratory pressures were measured in 44 adolescents with mild idiopathic scoliosis (spinal curvature less than 30 degrees). All were symptom free, but six (13.6%) showed a restrictive defect with forced vital capacity less than 80% of predicted. In 12 subjects (27.3%) maximum voluntary ventilation was reduced to less than 80% of predicted normal. Forced vital capacity was significantly correlated with maximum inspiratory pressure and with maximum expiratory pressure, measures of respiratory muscle strength, but was not related to the degree of thoracic curvature. When maximum inspiratory pressure and forced vital capacity were corrected for differences in body size these variables remained positively correlated, most significantly in the girls. These data indicate that ventilatory function may be impaired in mild, idiopathic scoliosis and that the force developed by the respiratory muscles is a more important determinant of this impairment than the radiologically determined degree of spinal curvature.

Hemodynamic effects of an inhaled beta-2 agonist

We examined echocardiographically in a single‐blind crossover trial the circulatory effects of an inhaled selective β2‐adrenergie bronchodilator, fenoterol. Eight healthy subjects were studied on the first and fourteenth day after randomly assigned therapy with either no drug or 400 μg fenoterol by metered dose inhaler four times a day. Heart rate (HR) and systolic (SBP) and diastolic (DBP) blood pressure responses to fenoterol were small (X ± SE; HR: +4 ± 1.3 bpm; SBP: +6 ± 1.3 mm Hg; DBP: —3 ± 1.4 mm Hg). In contrast, mean cardiac output increased 26% (1.1 ± 0.2 l/min), accompanied by an 18% fall in total peripheral vascular resistance (–6 ± 1.3 U), a 16% increase in stroke volume (+12 ±2.5 ml), and an 18% increase in the mean velocity of circumferential shortening (+0.2 ± 0.04 els). Responses varied widely among subjects; maximum observed increase in cardiac output was 117% (+5.48 l/min) in one subject. There was no evidence to suggest development of tolerance to these hemodynamic effects, as the response of measured variables did not differ after 2 wk of regular fenoterol therapy. We conclude that selective β2‐bronchodilators are not without potential for hemodynamically significant effects when taken by metered inhalers in recommended therapeutic doses and that the magnitude of such effects is underestimated when measured by HR and blood pressure changes.

The impact of budesonide and other inhaled corticosteroid therapies in the management of asthma in children and adults

BACKGROUND Since the recognition that asthma is characterized by extensive inflammation of the airways, the use of inhaled corticosteroids (ICSs) as controller therapy has become central to successful disease management. As the prevalence of asthma increases worldwide, there is concern about increasing numbers of patients with untreated or undertreated asthma, which may lead to deterioration in disease control, with direct effects on morbidity and mortality rates. The costs attributed to asthma translate into a considerable economic burden, from the direct costs of medical treatment to the costs incurred through lost work or school days. International treatment guidelines currently recommend early intervention with ICS therapy to improve lung function and disease control. OBJECTIVE This article reviews the role of therapy with ICSs, particularly budesonide, in improving the management of asthma in patients of all ages and in reducing the economic and social burdens of this disease. RESULTS Randomized, controlled clinical studies confirm the efficacy of early intervention with ICSs in patients with mild persistent asthma. Regular use of an ICS can reduce the number of exacerbations and hospitalizations in patients of all ages and with all disease severities. CONCLUSIONS Budesonide has a well-established efficacy and safety profile. Its once-daily dosing may contribute to improved adherence and cost-effectiveness.

Factors associated with undiagnosed and overdiagnosed COPD

Worldwide, studies have shown that about 60–86% of people with chronic obstructive pulmonary disease (COPD) have not been diagnosed, which represents a missed opportunity to decrease disease burden through optimal management, including smoking cessation support and prescription medications [1–3]. Overdiagnosed COPD is also common, with prevalence estimates ranging from 4% to 64% in the general population and primary care settings [4, 5]. Overdiagnosis can lead to unnecessary COPD treatments with their own risks and costs, poor health-related quality of life and missed detection and treatment of other diseases [6]. Several factors are associated with undiagnosed and overdiagnosed COPD http://ow.ly/4mW6lu

P233 Efficacy and safety of once-daily glycopyrronium compared with blinded tiotropium in patients with COPD: the GLOW5 study

Background Glycopyrronium, a once-daily long-acting muscarinic antagonist (LAMA), has demonstrated a similar efficacy and safety profile to open-label tiotropium in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD).1 The GLOW5 study compared the efficacy and safety of glycopyrronium with blinded tiotropium. Methods In this multicentre, 12-week, blinded study, patients ≥ 40 years with moderate-to-severe COPD (post-bronchodilator FEV1 ≥ 30% and < 80% of the predicted normal, post-bronchodilator FEV1/FVC < 0.70) and a smoking history of ≥10 pack-years were randomised to glycopyrronium 50μg (via Breezhaler® device) or tiotropium 18μg (via HandiHaler® device). The primary objective was to demonstrate non-inferiority of glycopyrronium versus tiotropium for trough FEV1 at Week 12 (non-inferiority margin: –50 mL). Other endpoints included FEV1 area under the curve from 0 to 4 hours (AUC0–4hr) on Day 1, Transition Dyspnoea Index (TDI), St Georges Respiratory Questionnaire (SGRQ), rescue medication use, exacerbation rate, safety and tolerability. Results Of the 657 patients randomised, (glycopyrronium [n = 327]; tiotropium [n = 330]; mean age: 63.5 years, mean post-bronchodilator FEV1: 53.5% predicted), 95.9% completed the study. Glycopyrronium demonstrated non-inferiority to tiotropium for trough FEV1 at Week 12 (Least Squares Mean [LSM] = 1.41L for both the groups; 95% confidence interval [CI]: –0.032, 0.031L). Glycopyrronium had a rapid onset of bronchodilation in the morning as demonstrated by a higher FEV1 AUC0–4hr on Day 1 compared to tiotropium (LSM treatment difference [Td] = 58mL; p < 0.001). At Week 12, TDI total score (Td = –0.188; p = 0.385), SGRQ total score (Td = 0.65; p = 0.488) and percentage of days with no rescue medication use (Td = –1.5; p = 0.528) were comparable between the groups. No significant treatment difference was observed with respect to rate of moderate/severe COPD exacerbations per year (glycopyrronium 0.38 versus tiotropium 0.35 [rate ratio = 1.10, 95% CI: 0.62, 1.93]; p = 0.754). Overall, the incidence of adverse events was similar in the glycopyrronium (40.4%) and tiotropium (40.6%) groups. Conclusion Glycopyrronium and blinded tiotropium showed similar improvements in lung function, dyspnoea, health status, exacerbation rate and rescue medication use, with a similar safety and tolerability profile. Onset of bronchodilation with glycopyrronium was significantly more rapid following the first dose. Reference Kerwin, E. et al. Eur Resp J 2012;40:1106–1114.