The role of modeling studies in asthma management and clinical decision-making: a Delphi survey of physician knowledge and perceptions.

OBJECTIVE: To investigate the knowledge and perceptions of physicians on the role of modeling studies in asthma, using a modified Delphi procedure. METHODS: Group opinions among a panel of respiratory experts were obtained using two online questionnaires and a virtual scientific workshop. A consensus was pre-defined as agreement by >75% of participants. RESULTS: From 26 experts who agreed to participate, 22 completed both surveys. At the end of the process, the panel rated their own understanding of modeling as good (77%) but that among physicians in general as poor (77%). Participants agreed that data from modeling studies should be used, at least sometimes, to inform treatment guidelines (91%) and could be useful for guiding clinical decisions (100%). Perceived barriers to using modeling studies were 'A lack of understanding' (81%) and 'A lack of standardized methodology' (82%). Based on data from two modeling studies, no consensus was reached on physicians recommending regular inhaled corticosteroids (ICS) versus as-needed therapy for patients with mild asthma, whereas 77% agreed that they would recommend regular ICS over maintenance and reliever therapy for ≥80% of their patients with moderate asthma. No consensus was reached on the value of modeling data in relation to empirical data. CONCLUSION: There is overall support among respiratory experts for the usefulness of modeling data to guide asthma treatment guidelines and clinical decision making. More publications on modeling data using robust models and accessible terminology will aid the understanding of physicians in general and help clarify the evidence-based value of modeling studies.

Cardiovascular risks in smokers treated with nicotine replacement therapy: a historical cohort study.

BACKGROUND: Previous research suggests exposure to nicotine replacement therapy (NRT) may be associated with an increased risk of cardiovascular disease (CVD). METHODS: Using data from the United Kingdom's Clinical Practice Research Datalink, this study aimed to evaluate CVD events and survival among individuals who attempted smoking cessation with the support of NRT compared with those aided by smoking cessation advice only. We studied CVD outcomes over 4 and 52 weeks in 50,214 smokers attempting to quit - 33,476 supported by smoking cessation advice and 16,738 with the support of NRT prescribed by their primary care physician. Patients were matched (2 smoking cessation advice patients:1 NRT patient) on demographic and clinical characteristics during a baseline year preceding their quit attempt. Cox proportional hazard regression, conditional negative binomial regression model, and conditional logistic regression were used to analyze data. RESULTS: Mean (standard deviation) population age was 47 (11.2) years; 51% were females. Time to first diagnosis of ischemic heart disease (IHD) among NRT and smoking cessation advice patients was similar within the first 4 weeks, but shorter for NRT patients over 52 weeks (hazard ratio [HR]: 1.35, 95% confidence interval [CI]: 1.03-1.77). A similar trend was observed for cerebrovascular disease (HR: 1.54, 95% CI: 1.08-2.19). NRT patients with a prior diagnosis of IHD or cerebrovascular disease had a higher rate of primary or secondary care consultations for IHD or cerebrovascular disease by 52 weeks (rate ratio: 1.50, 95% CI: 1.14-1.99). Patients prescribed NRT had a shorter survival time over 52 weeks, compared with those receiving advice only (HR: 1.39, 95% CI: 1.09-1.76). CONCLUSION: Our findings suggest that treatment with NRT over 4 weeks does not appear to have an impact on cardiovascular risks. However, a longer follow-up period of 52 weeks resulted in an increase in cardiovascular events for patients prescribed NRT, compared with those receiving smoking cessation advice only.

Prevalence of depression in COPD: A systematic review and meta-analysis of controlled studies.

BACKGROUND: Depression is frequently reported in association with COPD. However, the prevalence of depression in these patients ranges largely. This study aimed to systematically review the prevalence of depression in COPD and controls and to explore remaining causes of inter-study variability in the reported prevalence. METHODS: A systemic review of the literature and a meta-analysis was performed to evaluate the source of variability in the reported rates of depression in stable COPD. Main eligibility criteria were: controlled studies with a sample size >100, outpatients with COPD diagnosed by spirometry and, use of a validated depression screening instrument. RESULTS: From 1613 studies identified, eight controlled studies were included in the review. The number of participants in the pooled studies was of 5.552 COPD subjects and 5.211 controls. Using stricter criteria for study selection reduced the variability of the depression prevalence in COPD and controls, which was 27.1% [25.9-28.3] in COPD subjects and 10.0% [9.2-10.8] in the control group. The pooled odds ratio and 95% CI was 3.74 [2.4-5.9]. However, the heterogeneity across studies was high. Possible explanatory factor included sample sizes, COPD/controls ratio, smoker's/nonsmokers ratio and qualitative differences (source of subjects, instruments to screen depression, COPD severity, smoking status, and comorbidities). CONCLUSION: The study highlights the variability in estimates of depression prevalence in COPD. It could be explained by methodological differences across the included studies. This suggests that a standardization is critical to improve precision of the estimates.

The COPD Assessment Test: What Do We Know So Far?: A Systematic Review and Meta-Analysis About Clinical Outcomes Prediction and Classification of Patients Into GOLD Stages.

BACKGROUND: The COPD Assessment Test (CAT) was developed as a simple instrument to assess health status in patients with COPD. This study aimed to systematically review the determinants of the CAT score, its ability to predict clinical outcomes, and the agreement between CAT (≥ 10) and the modified Medical Research Council scale (mMRC ≥ 2) to categorize patients into the new Global Initiative for Chronic Obstructive Lung Disease classification system. METHODS: From January 1, 2009, to June 30, 2015, databases were searched for studies using CAT in adults with COPD and in general populations aiming to detect COPD. Two investigators independently screened, selected, and extracted data by using a standardized form. Where appropriate, the results were combined in a random effects meta-analysis. RESULTS: Of 453 studies, 17 were included, and eight were used in the meta-analysis. The models to predict the CAT score were able to explain < 50% of its variance. CAT scores can indicate risk of exacerbation, depression, acute deterioration in health status, and mortality. All studies found a different proportion of patients in each Global Initiative for Chronic Obstructive Lung Disease category using CAT ≥ 10 or mMRC ≥ 2. On average, the distribution was 13% different according to the instrument used. The κ agreement between CAT and mMRC ranged from 0.13 to 0.77. CONCLUSIONS: CAT may be used as a complementary tool in a patient's clinical assessment to predict COPD exacerbation, health status deterioration, depression, and mortality. The interpretation of this meta-analysis does not support the use of the recommended cutoff points of ≥10 for CAT and ≥2 for mMRC as equivalents for the purpose of assessing patient symptoms.

Current role of anticholinergic drugs in the treatment of asthma: key messages for clinical practice.

Anticholinergic bronchodilators such as tiotropium, a potent long-acting drug, are central to the symptomatic treatment of chronic obstructive pulmonary disease. Its role in asthma treatment has been recently investigated. This review critically evaluates documented evidence of clinical trials and assesses the therapeutic implications of anticholinergic drugs in asthma management. So far, the results of 10 Phases II and III randomized controlled trials evaluating the effect of adding tiotropium to the treatment of mild-to-moderate or severe asthma have been published. These trials had a duration of 4 to 52 weeks and involved 3368 subjects with mild-to-moderate asthma and 1019 subjects with severe asthma [corrected]. Also, 1 systematic review and 6 meta-analyses have appraised the results of published and unpublished trials investigating the role of tiotropium in asthma. The results of the trials in mild to moderate asthma showed that adding tiotropium to inhaled corticosteroids (ICSs) was not inferior to adding long-acting ß2-agonists (LABAs). In addition, the safety and efficacy of tiotropium were similar to those of salmeterol. The results of studies on severe asthma showed that adding tiotropium to a treatment with high doses of an ICS plus LABA results in further improvement in lung function, increases the time to the first severe exacerbation of asthma and to worsening of asthma, and improves asthma control. Except for dry mouth, the safety profile of tiotropium was similar to placebo both in moderate and in severe asthma. Adding tiotropium to an ICS or ICS plus LABA improves lung function, symptoms, and asthma control, and in severe asthma, it increases the time to exacerbations, with good safety profile. The effect seems independent of baseline characteristics such as age, level of bronchial obstruction, smoking status, allergic status, and bronchial reversibility.

Pentraxin 3 sputum levels differ in patients with chronic obstructive pulmonary disease vs asthma.

BACKGROUND: Immune response has been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD) and asthma. Pentraxin 3 (PTX3) is a multifunctional pattern recognition protein and an important component of the innate immune system that can be assessed in blood and induced sputum. OBJECTIVE: To determine whether PTX3 measured in induced sputum could discriminate patients with COPD from patients with asthma. METHODS: A cross-sectional study of 68 participants (27 with COPD, 25 with asthma, and 16 healthy controls) was performed. At study inclusion sputum was collected and total and differential cell numbers and PTX3 levels were determined. RESULTS: Pentraxin 3 was detected in 89% of patients with COPD, 56% of patients with asthma, and 19% of controls (P = .001). It discriminated participants with COPD (24.6 ng/mL, 0-384 ng/mL) from controls (0 ng/mL, 0-36 ng/mL, P < .001) and from participants with asthma (1.2 ng/mL, 0-100 ng/mL, P = .01; area under the receiver operating curve 0.82 [0.71-0.94]). Regression analyses determined that sputum PTX3 and neutrophil counts were independently associated with COPD. In addition, PTX3 levels were independently associated with COPD severity. CONCLUSION: Pentraxin 3 sputum levels are increased in patients with COPD and has good power to discriminate these patients from patients with asthma and healthy individuals.

Disparate geographic prevalences of asthma, allergic rhinoconjunctivitis and atopic eczema among adolescents in five Canadian cities.

To assess concordance of prevalence rates of asthma, allergic rhinoconjunctivitis and atopic eczema symptoms among adolescents in five Canadian cities. The International Study of Asthma and Allergies in Childhood Phase 3 written questionnaires were answered by 8334 adolescents aged 13 to 14 in Vancouver, Saskatoon, Winnipeg, Hamilton and Halifax, Canada. Prevalence rates of current symptoms ranged from 13.7-33.0% for wheezing, 14.6-22.6% for allergic rhinoconjunctivitis and 8.2-10.4% for atopic eczema. Using Hamilton as reference, the prevalence of wheezing was significantly higher in Halifax (OR = 1.58; 95% CI 1.36-1.84) and Saskatoon (1.27; 1.07-1.50) and significantly lower in Vancouver (0.51; 0.44-0.59). In contrast, allergic rhinoconjunctivitis was significantly more prevalent in Winnipeg (1.39; 1.16-1.68) and Halifax (1.36; 1.14-1.61) and trended lower in Saskatoon (0.81; 0.66-1.00). Atopic eczema was significantly more prevalent in Winnipeg (1.31; 1.01-1.69) and Vancouver (1.28; 1.04-1.58). Multivariable logistic regression analyses showed the region of residence, being born in Canada, recent use of acetaminophen and heavy exposure to traffic exhaust were significantly associated with all three allergic conditions, while obesity and having two or more smokers at home was only associated with increased risk for wheezing. Chinese ethnicity decreased that risk. Among five Canadian centres, the highest prevalence rates of allergic rhinoconjunctivitis or atopic eczema were not observed in the same regions as the highest prevalence rates of wheezing. This disparity in regional variations in the prevalence rates suggests dissimilar risk factors for the development or expression of wheezing (asthma), allergic rhinoconjunctivitis and atopic eczema.

Mepolizumab for prednisone-dependent asthma with sputum eosinophilia.

BACKGROUND: Eosinophilic inflammation, which may be a consequence of interleukin-5 action, is a characteristic feature of some forms of asthma. However, in three previous clinical trials involving patients with asthma, blockade of this cytokine did not result in a significant improvement in outcomes. We studied the prednisone-sparing effect of mepolizumab, a monoclonal antibody against interleukin-5, in a rare subgroup of patients who have sputum eosinophilia and airway symptoms despite continued treatment with prednisone. Secondary objectives were to examine its effect on the number of eosinophils in sputum and blood, symptoms, and airflow limitation. METHODS: In this randomized, double-blind, parallel-group trial involving patients with persistent sputum eosinophilia and symptoms despite prednisone treatment, we assigned 9 patients to receive mepolizumab (administered in five monthly infusions of 750 mg each) and 11 patients to receive placebo. RESULTS: There were 12 asthma exacerbations in 10 patients who received placebo, 9 of whom had sputum eosinophilia at the time of exacerbation. In comparison, only one patient who received mepolizumab had an asthma exacerbation, and this episode was not associated with sputum eosinophilia (P=0.002). Patients who received mepolizumab were able to reduce their prednisone dose by a mean (+/-SD) of 83.8+/-33.4% of their maximum possible dose, as compared with 47.7+/-40.5% in the placebo group (P=0.04). The use of mepolizumab was associated with a significant decrease in the number of sputum and blood eosinophils. Improvements in eosinophil numbers, asthma control, and forced expiratory volume in 1 second were maintained for 8 weeks after the last infusion. There were no serious adverse events. CONCLUSIONS: Mepolizumab reduced the number of blood and sputum eosinophils and allowed prednisone sparing in patients who had asthma with sputum eosinophilia despite prednisone treatment. (ClinicalTrials.gov number, NCT00292877.)