M. Diane Lougheed

Canadian Thoracic Society 2012 guideline update: Diagnosis and management of asthma in preschoolers, children and adults

BACKGROUND In 2010, the Canadian Thoracic Society (CTS) published a Consensus Summary for the diagnosis and management of asthma in children six years of age and older, and adults, including an updated Asthma Management Continuum. The CTS Asthma Clinical Assembly subsequently began a formal clinical practice guideline update process, focusing, in this first iteration, on topics of controversy and⁄or gaps in the previous guidelines. METHODS Four clinical questions were identified as a focus for the updated guideline: the role of noninvasive measurements of airway inflammation for the adjustment of anti-inflammatory therapy; the initiation of adjunct therapy to inhaled corticosteroids (ICS) for uncontrolled asthma; the role of a single inhaler of an ICS⁄long-acting beta(2)-agonist combination as a reliever, and as a reliever and a controller; and the escalation of controller medication for acute loss of asthma control as part of a self-management action plan. The expert panel followed an adaptation process to identify and appraise existing guidelines on the specified topics. In addition, literature searches were performed to identify relevant systematic reviews and randomized controlled trials. The panel formally assessed and graded the evidence, and made 34 recommendations. RESULTS The updated guideline recommendations outline a role for inclusion of assessment of sputum eosinophils, in addition to standard measures of asthma control, to guide adjustment of controller therapy in adults with moderate to severe asthma. Appraisal of the evidence regarding which adjunct controller therapy to add to ICS and at what ICS dose to begin adjunct therapy in children and adults with poor asthma control supported the 2010 CTS Consensus Summary recommendations. New recommendations for the adjustment of controller medication within written action plans are provided. Finally, priority areas for future research were identified. CONCLUSIONS The present clinical practice guideline is the first update of the CTS Asthma Guidelines following the Canadian Respiratory Guidelines Committees new guideline development process. Tools and strategies to support guideline implementation will be developed and the CTS will continue to regularly provide updates reflecting new evidence.

Canadian Thoracic Society Asthma Management Continuum – 2010 Consensus Summary for Children Six Years of Age and Over, and Adults

BACKGROUND/OBJECTIVE To integrate new evidence into the Canadian Asthma Management Continuum diagram, encompassing both pediatric and adult asthma. METHODS The Canadian Thoracic Society Asthma Committee members, comprised of experts in pediatric and adult respirology, allergy and immunology, emergency medicine, general pediatrics, family medicine, pharmacoepidemiology and evidence-based medicine, updated the continuum diagram, based primarily on the 2008 Global Initiative for Asthma guidelines, and performed a focused review of literature pertaining to key aspects of asthma diagnosis and management in children six years of age and over, and adults. RESULTS In patients six years of age and over, management of asthma begins with establishing an accurate diagnosis, typically by supplementing medical history with objective measures of lung function. All patients and caregivers should receive self-management education, including a written action plan. Inhaled corticosteroids (ICS) remain the first-line controller therapy for all ages. When asthma is not controlled with a low dose of ICS, the literature supports the addition of long-acting beta2-agonists in adults, while the preferred approach in children is to increase the dose of ICS. Leukotriene receptor antagonists are acceptable as second-line monotherapy and as an alternative add-on therapy in both age groups. Antiimmunoglobulin E therapy may be of benefit in adults, and in children 12 years of age and over with difficult to control allergic asthma, despite high-dose ICS and at least one other controller. CONCLUSIONS The foundation of asthma management is establishing an accurate diagnosis based on objective measures (eg, spirometry) in individuals six years of age and over. Emphasis is placed on the similarities and differences between pediatric and adult asthma management approaches to achieve asthma control.

Exacerbation frequency and clinical outcomes in adult patients with cystic fibrosis

Background Despite advances in treatment of cystic fibrosis (CF), pulmonary exacerbations remain common. The aim of this study was to determine if frequent pulmonary exacerbations are associated with greater declines in lung function, or an accelerated time to death or lung transplantation in adults with CF. Methods A 3-year prospective cohort study was conducted on 446 adult patients with CF from Ontario, Canada who could spontaneously produce sputum. Patients enrolled from 2005 to 2008 and were stratified into groups based upon their exacerbation rates over the 3 year study: <1 exacerbation/year (n=140), 1–2 exacerbations/year (n=160) and >2 exacerbations/year (n=146). Exacerbations were defined as acute/subacute worsening of respiratory symptoms severe enough to warrant oral or intravenous antibiotics. Patient-related factors associated with frequent exacerbations were determined, and clinical outcomes were compared among the three exacerbation groups. Results Patients with frequent exacerbations were more likely to be female, diabetic and have poorer baseline lung function. Patients with >2 exacerbations/year had an increased risk of experiencing a 5% decline from baseline forced expiratory volume in 1 s (FEV1); unadjusted HR 1.47 (95% CI 1.07 to 2.01, p=0.02), adjusted HR 1.55 (95% CI 1.10 to 2.18, p=0.01) compared with patients with <1 exacerbation/year. Patients with >2 exacerbations/year also had an increased risk of lung transplant or death over the 3 year study; unadjusted HR 12.74 (95% CI 3.92 to 41.36, p<0.0001), adjusted HR 4.05 (95% CI 1.15 to 14.28, p=0.03). Conclusions Patients with CF with frequent exacerbations appear to experience an accelerated decline in lung function, and they have an increased 3 year risk of death or lung transplant.

Infection With Transmissible Strains of Pseudomonas aeruginosa and Clinical Outcomes in Adults With Cystic Fibrosis

CONTEXT Studies from Australia and the United Kingdom have shown that some patients with cystic fibrosis are infected with common transmissible strains of Pseudomonas aeruginosa. OBJECTIVES To determine the prevalence and incidence of infection with transmissible strains of P. aeruginosa and whether presence of the organism was associated with adverse clinical outcomes in Canada. DESIGN, SETTING, AND PARTICIPANTS Prospective observational cohort study of adult patients cared for at cystic fibrosis clinics in Ontario, Canada, with enrollment from September 2005 to September 2008. Sputum was collected at baseline, 3 months, and yearly thereafter for 3 years; and retrieved P. aeruginosa isolates were genotyped. Vital status (death or lung transplant) was assessed for all enrolled patients until December 31, 2009. MAIN OUTCOME MEASURES Incidence and prevalence of P. aeruginosa isolation, rates of decline in lung function, and time to death or lung transplantation. RESULTS Of the 446 patients with cystic fibrosis studied, 102 were discovered to be infected with 1 of 2 common transmissible strains of P. aeruginosa at study entry. Sixty-seven patients were infected with strain A (15%), 32 were infected with strain B (7%), and 3 were simultaneously infected with both strains (0.6%). Strain A was found to be genetically identical to the Liverpool epidemic strain but strain B has not been previously described as an epidemic strain. The incidence rate of new infections with these 2 transmissible strains was relatively low (7.0 per 1000 person-years; 95% confidence interval [CI], 1.8-12.2 per 1000 person-years). Compared with patients infected with unique strains of P. aeruginosa, patients infected with the Liverpool epidemic strain (strain A) and strain B had similar declines in lung function (difference in decline in percent predicted forced expiratory volume in the first second of expiration of 0.64% per year [95% CI, -1.52% to 2.80% per year] and 1.66% per year [95% CI, -1.00% to 4.30%], respectively). However, the 3-year rate of death or lung transplantation was greater in those infected with the Liverpool epidemic strain (18.6%) compared with those infected with unique strains (8.7%) (adjusted hazard ratio, 3.26 [95% CI, 1.41 to 7.54]; P = .01). CONCLUSIONS A common strain of P. aeruginosa (Liverpool epidemic strain/strain A) infects patients with cystic fibrosis in Canada and the United Kingdom. Infection with this strain in adult Canadian patients with cystic fibrosis was associated with a greater risk of death or lung transplantation.

Variations and Gaps in Management of Acute Asthma in Ontario Emergency Departments

BACKGROUND Variation in hospitalization rates for acute asthma in Ontario may reflect gaps between evidence and current emergency department (ED) management. We investigated ED management of asthma and differences in practice patterns for pediatric (< 20 years old) and adult (> or = 20 years old) patients in Ontario EDs. METHOD Patient characteristics and ED management during a 1-year period were assessed by questionnaire and chart abstractions in a stratified sample of 16 Ontario hospitals. Variation between sites was assessed by one-way analysis of variance, Kruskal-Wallis test, or chi(2) test. RESULTS Reported results are based on the first of 2,671 pediatric (42.0% female) and 2,078 adult (66.7% female) visits with a corresponding questionnaire. Asthma severity, comorbidities, access to care, and prehospital management varied significantly among sites (all p < 0.001). Documentation of peak expiratory flow (27.2% of pediatric [age > or = 7] and 44.3% of adult charts), use of systemic steroids in ED (35.2% pediatric and 33.0% adult charts) and on discharge (31.7% pediatric and 33.2% adult charts), and referrals to asthma services (2.8% pediatric and 2.7% adult charts) varied among sites (all p < 0.001). Admission (%) was directly related to time to receive systemic steroids in ED in adults (r = 0.76; p = 0.004). Repeat ED visits (%) were inversely related to new inhaled steroid prescription on discharge in adults (r = -0.64; p = 0.02). CONCLUSIONS Knowledge translation initiatives are warranted to increase adherence with best practices in emergency management of asthma (such as objective assessment of airflow rates, use of systemic steroids, and referrals) in order to reduce variations in care and improve outcomes of severe acute asthma.

Airway Hyperresponsiveness in Asthma: Mechanisms, Clinical Significance, and Treatment

Airway hyperresponsiveness (AHR) and airway inflammation are key pathophysiological features of asthma. Bronchial provocation tests (BPTs) are objective tests for AHR that are clinically useful to aid in the diagnosis of asthma in both adults and children. BPTs can be either “direct” or “indirect,” referring to the mechanism by which a stimulus mediates bronchoconstriction. Direct BPTs refer to the administration of pharmacological agonist (e.g., methacholine or histamine) that act on specific receptors on the airway smooth muscle. Airway inflammation and/or airway remodeling may be key determinants of the response to direct stimuli. Indirect BPTs are those in which the stimulus causes the release of mediators of bronchoconstriction from inflammatory cells (e.g., exercise, allergen, mannitol). Airway sensitivity to indirect stimuli is dependent upon the presence of inflammation (e.g., mast cells, eosinophils), which responds to treatment with inhaled corticosteroids (ICS). Thus, there is a stronger relationship between indices of steroid-sensitive inflammation (e.g., sputum eosinophils, fraction of exhaled nitric oxide) and airway sensitivity to indirect compared to direct stimuli. Regular treatment with ICS does not result in the complete inhibition of responsiveness to direct stimuli. AHR to indirect stimuli identifies individuals that are highly likely to have a clinical improvement with ICS therapy in association with an inhibition of airway sensitivity following weeks to months of treatment with ICS. To comprehend the clinical utility of direct or indirect stimuli in either diagnosis of asthma or monitoring of therapeutic intervention requires an understanding of the underlying pathophysiology of AHR and mechanisms of action of both stimuli.

Effects of Obesity on Perceptual and Mechanical Responses to Bronchoconstriction in Asthma

RATIONALE The influence of obesity on the perception of respiratory discomfort during acute bronchoconstriction in asthma is unknown. OBJECTIVES We hypothesized that the respiratory impairment associated with an increased body mass index (BMI) would predispose to greater perceived symptom intensity during acute airway narrowing. We therefore compared relationships between induced changes in dyspnea intensity and lung function during methacholine (MCh) bronchoprovocation in obese (OBA) and normal-weight (NWA) individuals with asthma of mild to moderate severity. METHODS High-dose MCh challenge tests to a maximum 50% decrease in FEV(1) were conducted in 51 NWA (BMI, 18.5-24.9 kg/m(2); 29% male) and 45 OBA (BMI, 30.1-51.4 kg/m(2); 33% male) between 20 and 60 years of age. Serial spirometry, inspiratory capacity (IC), plethysmographic end-expiratory lung volume (EELV) and dyspnea intensity using the Borg scale were measured throughout bronchoprovocation. MEASUREMENTS AND MAIN RESULTS Spirometry and airway sensitivity were similar in both groups; baseline EELV was lower (P < 0.0005) and IC was higher (P = 0.007) in OBA compared with NWA. From baseline to PC(20), EELV increased more in OBA (20% predicted) than NWA (13% predicted) (P = 0.008) with concomitant greater reductions in IC (P < 0.0005). Dyspnea ratings were not different for a given FEV(1) or IC across groups. By mixed effects regression analysis, relationships between induced dyspnea and changes in lung function parameters were not influenced by BMI, sex, or their interaction. CONCLUSIONS Perceptual responses to MCh-induced bronchoconstriction and lung hyperinflation were similar in obese and normal-weight individuals with asthma despite significant group differences in baseline lung volumes.

Progression from Asthma to Chronic Obstructive Pulmonary Disease. Is Air Pollution a Risk Factor

RATIONALE Individuals with asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS), have more rapid decline in lung function, more frequent exacerbations, and poorer quality of life than those with asthma or COPD alone. Air pollution exposure is a known risk factor for asthma and COPD; however, its role in ACOS is not as well understood. OBJECTIVES To determine if individuals with asthma exposed to higher levels of air pollution have an increased risk of ACOS. METHODS Individuals who resided in Ontario, Canada, aged 18 years or older in 1996 with incident asthma between 1996 and 2009 who participated in the Canadian Community Health Survey were identified and followed until 2014 to determine the development of ACOS. Data on exposures to fine particulate matter (PM2.5) and ozone (O3) were obtained from fixed monitoring sites. Associations between air pollutants and ACOS were evaluated using Cox regression models. MEASUREMENTS AND MAIN RESULTS Of the 6,040 adults with incident asthma who completed the Canadian Community Health Survey, 630 were identified as ACOS cases. Compared with those without ACOS, the ACOS population had later onset of asthma, higher proportion of mortality, and more frequent emergency department visits before COPD diagnosis. The adjusted hazard ratios of ACOS and cumulative exposures to PM2.5 (per 10 μg/m(3)) and O3 (per 10 ppb) were 2.78 (95% confidence interval, 1.62-4.78) and 1.31 (95% confidence interval, 0.71-2.39), respectively. CONCLUSIONS Individuals exposed to higher levels of air pollution had nearly threefold greater odds of developing ACOS. Minimizing exposure to high levels of air pollution may decrease the risk of ACOS.

Canadian Thoracic Society 2012 Guideline Update: Diagnosis and Management of Asthma in Preschoolers, Children and Adults: Executive Summary

BACKGROUND: In 2010, the Canadian Thoracic Society (CTS) published a Consensus Summary for the diagnosis and management of asthma in children six years of age and older, and adults, including an updated Asthma Management Continuum. The CTS Asthma Clinical Assembly subsequently began a formal clinical practice guideline update process, focusing, in this first iteration, on topics of controversy and/or gaps in the previous guidelines.

Evidence-based performance indicators of primary care for asthma: a modified RAND Appropriateness Method

PURPOSE To develop evidence-based performance indicators that measure the quality of primary care for asthma. DATA SOURCES Cochrane Database of Systematic Reviews, MEDLINE, EMBASE and CINAHL for peer-reviewed articles published in 1998-2008 and five national/global asthma management guidelines. STUDY SELECTION Articles with a focus on current asthma performance indicators recognized or used in community and primary care settings. Data extraction Modified RAND Appropriateness METHOD was used. The work described herein was conducted in Canada in 2008. Five clinician experts conducted the systematic literature review. Asthma-specific performance indicators were developed and the strength of supporting evidence summarized. A survey was created and mailed to 17 expert panellists of various disciplines, asking them to rate each indicator using a 9-point Likert scale. Percentage distribution of the Likert scores were generated and given to the panellists before a face-to-face meeting, which was held to assess consensus. At the meeting, they ranked all indicators based on their reliability, validity, availability and feasibility. RESULTS Literature search yielded 1228 articles, of which 135 were used to generate 45 performance indicators in five domains: access to care, clinical effectiveness, patient centeredness, system integration and coordination and patient safety. The top five ranked indicators were: Asthma Education from Certified Asthma Educator, Pulmonary Function Monitoring, Asthma Control Monitoring, Controller Medication Use and Asthma Control. CONCLUSION The top 15 ranked indicators are recommended for implementation in primary care to measure asthma care delivery, respiratory health outcomes and establish benchmarks for optimal health service delivery over time and across populations.