Chronic obstructive pulmonary disease (COPD) remains undiagnosed in many individuals with persistent airflow limitation. These individuals may be susceptible to exacerbation-like respiratory events ...that consume health care resources.
To compare exacerbation-like respiratory events, event prevalence, and differences in the odds of using medication and/or health services between subjects with diagnosed and undiagnosed COPD.
Subjects sampled from the general population participating in the CanCOLD (Canadian Cohort Obstructive Lung Disease) study, with at least 12 months of exacerbation-event follow-up who were classified as having physician-diagnosed or undiagnosed COPD were assessed. Exacerbation-like respiratory events were captured using a questionnaire administered every 3 months.
A total of 355 subjects were undiagnosed and 150 were diagnosed with COPD. Undiagnosed subjects were less symptomatic and functionally impaired, had been prescribed fewer respiratory medications, and had better health status. The incidence of reported exacerbation-like events was higher in diagnosed subjects and increased in both groups with the severity of airflow obstruction. Although subjects with diagnosed COPD were more often prescribed medication for exacerbation events, health service use for exacerbation events was similar in both groups.
Most subjects with COPD in Canada remain undiagnosed. These subjects are less symptomatic and impaired, which may partly explain lack of diagnosis. Although patients with undiagnosed COPD experience fewer exacerbations than those with diagnosed COPD, they use a similar amount of health services for exacerbation events; thus, the overall health system burden of exacerbations in those with undiagnosed COPD is considerable.
Ambient air pollution has been suggested as a risk factor for chronic obstructive pulmonary disease (COPD). However, there is a lack of longitudinal studies to support this assertion.
To investigate ...the associations of long-term exposure to elevated traffic-related air pollution and woodsmoke pollution with the risk of COPD hospitalization and mortality.
This population-based cohort study included a 5-year exposure period and a 4-year follow-up period. All residents aged 45-85 years who resided in Metropolitan Vancouver, Canada, during the exposure period and did not have known COPD at baseline were included in this study (n = 467,994). Residential exposures to traffic-related air pollutants (black carbon, particulate matter <2.5 μm in aerodynamic diameter, nitrogen dioxide, and nitric oxide) and woodsmoke were estimated using land-use regression models and integrating changes in residences during the exposure period. COPD hospitalizations and deaths during the follow-up period were identified from provincial hospitalization and death registration databases.
An interquartile range elevation in black carbon concentrations (0.97 × 10(-5)/m, equivalent to 0.78 μg/m(3) elemental carbon) was associated with a 6% (95% confidence interval, 2-10%) increase in COPD hospitalizations and a 7% (0-13%) increase in COPD mortality after adjustment for covariates. Exposure to higher levels of woodsmoke pollution (tertile 3 vs. tertile 1) was associated with a 15% (2-29%) increase in COPD hospitalizations. There were positive exposure-response trends for these observed associations.
Ambient air pollution, including traffic-related fine particulate pollution and woodsmoke pollution, is associated with an increased risk of COPD.
In patients with mild asthma, as-needed use of an inhaled glucocorticoid plus a fast-acting β
-agonist may be an alternative to conventional treatment strategies.
We conducted a 52-week, double-blind ...trial involving patients 12 years of age or older with mild asthma. Patients were randomly assigned to one of three regimens: twice-daily placebo plus terbutaline (0.5 mg) used as needed (terbutaline group), twice-daily placebo plus budesonide-formoterol (200 μg of budesonide and 6 μg of formoterol) used as needed (budesonide-formoterol group), or twice-daily budesonide (200 μg) plus terbutaline used as needed (budesonide maintenance group). The primary objective was to investigate the superiority of as-needed budesonide-formoterol to as-needed terbutaline with regard to electronically recorded weeks with well-controlled asthma.
A total of 3849 patients underwent randomization, and 3836 (1277 in the terbutaline group, 1277 in the budesonide-formoterol group, and 1282 in the budesonide maintenance group) were included in the full analysis and safety data sets. With respect to the mean percentage of weeks with well-controlled asthma per patient, budesonide-formoterol was superior to terbutaline (34.4% vs. 31.1% of weeks; odds ratio, 1.14; 95% confidence interval CI, 1.00 to 1.30; P=0.046) but inferior to budesonide maintenance therapy (34.4% and 44.4%, respectively; odds ratio, 0.64; 95% CI, 0.57 to 0.73). The annual rate of severe exacerbations was 0.20 with terbutaline, 0.07 with budesonide-formoterol, and 0.09 with budesonide maintenance therapy; the rate ratio was 0.36 (95% CI, 0.27 to 0.49) for budesonide-formoterol versus terbutaline and 0.83 (95% CI, 0.59 to 1.16) for budesonide-formoterol versus budesonide maintenance therapy. The rate of adherence in the budesonide maintenance group was 78.9%. The median metered daily dose of inhaled glucocorticoid in the budesonide-formoterol group (57 μg) was 17% of the dose in the budesonide maintenance group (340 μg).
In patients with mild asthma, as-needed budesonide-formoterol provided superior asthma-symptom control to as-needed terbutaline, assessed according to electronically recorded weeks with well-controlled asthma, but was inferior to budesonide maintenance therapy. Exacerbation rates with the two budesonide-containing regimens were similar and were lower than the rate with terbutaline. Budesonide-formoterol used as needed resulted in substantially lower glucocorticoid exposure than budesonide maintenance therapy. (Funded by AstraZeneca; SYGMA 1 ClinicalTrials.gov number, NCT02149199 .).
Greater precision in asthma exacerbation risk prediction may improve outcomes. We sought to identify clinical characteristics and biomarkers associated with elevated exacerbation risk in patients ...with severe, uncontrolled asthma.
Data were pooled from seven similarly designed phase II and III randomised controlled clinical trials of biologic therapies for the treatment of severe, uncontrolled asthma that enrolled comparable patient populations. Annualised asthma exacerbation rates (AAERs) for patients randomised to placebo were assessed by baseline clinical characteristics, and by biomarker concentrations at baseline and over the study duration.
The AAER for the 2016 patients in the combined placebo group was 0.91 (95% CI 0.84‒0.98). Baseline characteristics associated with greater AAER were frequent or severe exacerbations within the prior 12 months, nasal polyposis, maintenance oral corticosteroid use, Asian race and Asian or Western European region. AAER increased with baseline blood eosinophil counts and exhaled nitric oxide fraction (
) concentration, with the greatest AAER occurring for patients with eosinophils ≥300 cells·μL
and
≥50 ppb. No relationship was observed between baseline serum IgE concentration and AAER. Combining type 2 inflammation criteria for eosinophils and
had greater prognostic value than either biomarker alone. Persistent eosinophil and
elevations throughout the study period were associated with greater AAER.
Exacerbation history, maintenance corticosteroid use, nasal polyposis, Asian race, geographic region, and elevations in blood eosinophil counts and
concentrations (particularly when combined and/or persistently achieving type 2 inflammation criteria) were associated with increased exacerbation risk in patients with severe, uncontrolled asthma.
Patients with mild asthma often rely on inhaled short-acting β
-agonists for symptom relief and have poor adherence to maintenance therapy. Another approach might be for patients to receive a ...fast-acting reliever plus an inhaled glucocorticoid component on an as-needed basis to address symptoms and exacerbation risk.
We conducted a 52-week, double-blind, multicenter trial involving patients 12 years of age or older who had mild asthma and were eligible for treatment with regular inhaled glucocorticoids. Patients were randomly assigned to receive twice-daily placebo plus budesonide-formoterol (200 μg of budesonide and 6 μg of formoterol) used as needed or budesonide maintenance therapy with twice-daily budesonide (200 μg) plus terbutaline (0.5 mg) used as needed. The primary analysis compared budesonide-formoterol used as needed with budesonide maintenance therapy with regard to the annualized rate of severe exacerbations, with a prespecified noninferiority limit of 1.2. Symptoms were assessed according to scores on the Asthma Control Questionnaire-5 (ACQ-5) on a scale from 0 (no impairment) to 6 (maximum impairment).
A total of 4215 patients underwent randomization, and 4176 (2089 in the budesonide-formoterol group and 2087 in the budesonide maintenance group) were included in the full analysis set. Budesonide-formoterol used as needed was noninferior to budesonide maintenance therapy for severe exacerbations; the annualized rate of severe exacerbations was 0.11 (95% confidence interval CI, 0.10 to 0.13) and 0.12 (95% CI, 0.10 to 0.14), respectively (rate ratio, 0.97; upper one-sided 95% confidence limit, 1.16). The median daily metered dose of inhaled glucocorticoid was lower in the budesonide-formoterol group (66 μg) than in the budesonide maintenance group (267 μg). The time to the first exacerbation was similar in the two groups (hazard ratio, 0.96; 95% CI, 0.78 to 1.17). The change in ACQ-5 score showed a difference of 0.11 units (95% CI, 0.07 to 0.15) in favor of budesonide maintenance therapy.
In patients with mild asthma, budesonide-formoterol used as needed was noninferior to twice-daily budesonide with respect to the rate of severe asthma exacerbations during 52 weeks of treatment but was inferior in controlling symptoms. Patients in the budesonide-formoterol group had approximately one quarter of the inhaled glucocorticoid exposure of those in the budesonide maintenance group. (Funded by AstraZeneca; SYGMA 2 ClinicalTrials.gov number, NCT02224157 .).
Health literacy plays a crucial role in chronic disease management. To comprehensively manage chronic conditions on a daily basis, individuals must be able to assess, understand, evaluate, and use ...health information. Several key publications emphasize that health literacy is not merely a matter of individual skills but that it is highly dependent on the accessibility of health-care systems, the communication skills of health-care professionals, and the level of complexity of the health information. However, the literature indicates that health literacy is mainly framed and measured as an individual attribute in research. Focusing health literacy research solely on the individual, rather than also including the health-care context, limits our understanding of the type of actions that should be undertaken to facilitate a person's access to and understanding, evaluation and use of health information. This commentary highlights the importance of interpreting the concept of health literacy as a dynamic construct that emerges from the interaction between patients/citizens and health-care systems, organizations, and professionals. This approach has the potential to fill a gap in our understanding of the link between health literacy and chronic disease management. Such an understanding would facilitate the development of comprehensive health literacy measurement instruments and interventions to enhance health literacy.
Benralizumab is a humanised, afucosylated, anti-interleukin-5 receptor α monoclonal antibody that induces direct, rapid, and nearly complete depletion of eosinophils. We aimed to assess the efficacy ...and safety of benralizumab as add-on therapy for patients with severe, uncontrolled asthma and elevated blood eosinophil counts. Methods In this randomised, double-blind, parallel-group, placebo-controlled, phase 3 study (CALIMA) undertaken at 303 sites in 11 countries, we enrolled patients aged 12-75 years with severe asthma uncontrolled by medium-dosage to high-dosage inhaled corticosteroids plus long-acting β...-agonists (ICS plus LABA) and a history of two or more exacerbations in the previous year. Patients were randomly assigned (1:1:1) to receive 56 weeks of benralizumab 30 mg every 4 weeks (Q4W), benralizumab 30 mg every 8 weeks (Q8W; first three doses 4 weeks apart), or placebo (all subcutaneous injection). Patients were stratified (2:1) by baseline blood eosinophil counts 300 cells per μL or greater and less than 300 cells per μL, respectively. Patients and study centre staff were masked to treatment allocation. The primary endpoint was annual exacerbation rate ratio versus placebo for patients receiving high-dosage ICS plus LABA with baseline blood eosinophils 300 cells per μL or greater (intention-to-treat analysis). Key secondary endpoints were pre-bronchodilator forced expiratory volume in 1 s (FEV1) and total asthma symptom score. This study is registered withClinicalTrials.gov, numberNCT01914757. Findings Between Aug 21, 2013, and March 16, 2015, 2505 patients were enrolled, of whom 1306 patients were randomised; 425 patients were randomly assigned to and received benralizumab 30 mg Q4W, 441 to benralizumab 30 mg Q8W, and 440 to placebo. 728 patients were included in the primary analysis population. Benralizumab resulted in significantly lower annual exacerbation rates with the Q4W regimen (rate 0·60 95% CI 0·48-0·74, rate ratio 0·64 95% CI 0·49-0·85, p=0·0018, n=241) and Q8W regimen (rate 0·66 95% CI 0·54-0·82, rate ratio 0·72 95% CI 0·54-0·95, p=0·0188, n=239) compared with placebo (rate 0·93 95% CI 0·77-1·12, n=248). Benralizumab also significantly improved pre-bronchodilator FEV1(Q4W and Q8W) and total asthma symptom score (Q8W only) in these patients. The most common adverse events were nasopharyngitis (90 21% in the Q4W group, 79 18% in the Q8W group, and 92 21% in the placebo group) and worsening asthma (61 14% in the Q4W group, 47 11% in the Q8W group, and 68 15% in the group). Interpretation Benralizumab significantly reduced annual exacerbation rates and was generally well tolerated for patients with severe, uncontrolled asthma with blood eosinophils 300 cells per μL or greater. Our data further refine the patient population likely to receive the greatest benefit from benralizumab treatment. Funding AstraZeneca and Kyowa Hakko Kirin.
Asthma is associated with enormous healthcare expenditures that include both direct and indirect costs. It is also associated with the loss of future potential earnings related to both morbidity and ...mortality. The objective of the study is to determine the burden of disease costs associated with asthma.
We performed a systematic search of MEDLINE, EMBASE, CINAHL, CDSR, OHE-HEED, and Web of Science Databases between 1966 and 2008.
Sixty-eight studies met the inclusion criteria. Hospitalization and medications were found to be the most important cost driver of direct costs. Work and school loss accounted for the greatest percentage of indirect costs. The cost of asthma was correlated with comorbidities, age, and disease severity.
Despite the availability of effective preventive therapy, costs associated with asthma are increasing. Strategies including education of patients and physicians, and regular follow-up are required to reduce the economic burden of asthma.
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