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Background Patients living with chronic obstructive pulmonary disease (COPD) are at an increased risk of lung cancer. A common comorbidity of COPD is cardiovascular disease; as such, COPD patients often receive statins. This study sought to understand the association between statin exposure and lung cancer risk in a population-based cohort of COPD patients. Methods We identified a population-based cohort of COPD patients based on having filled at least three prescriptions for an anticholinergic or short-acting beta-agonist (SABA). We used an array of methods of defining medication exposure including three conventional methods (ever statin exposure, cumulative duration of use, and cumulative dose) and two novel methods (recency-weighted cumulative duration of use and recency-weighted cumulative dose). To assess residual confounding, a negative control exposure was used to test the validity of our results. All exposure variables were time-dependent. Results The population-based cohort of COPD had 39,879 patients with mean age of 70.6 (SD: 11.2) years and, of which, 53.5% were female. There were 12,469 patients who received at least one statin prescription. Results from the reference case multivariable analysis indicated a reduced risk from statin exposure (HR: 0.85 (95% CI: 0.73–1.00) in COPD patients, but this result not statistically significant. Using the two recency-weighted modelling approaches, statin exposure was associated with a statistically significant reduction in lung cancer risk (recency-weighted cumulative dose, HR: 0.85 (95% CI: 0.77–0.93) and recency-weighted cumulative duration of use, HR: 0.97 (95% CI: 0.96–0.99). Multivariable analysis incorporating the negative control exposure was not statistically significant (HR: 0.89 (95% CI: 0.75–1.10). Conclusions The results of this population-based analysis indicate that statin use in COPD patients may reduce the risk of lung cancer. While the effect was not statistically significantly across all exposure definitions, the overall results support the hypothesis that COPD patients might benefit from statin therapy.

Background Etiologies of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are heterogeneous. We phenotyped severe AECOPD based on molecular pathogen detection of sputum samples collected at hospitalization of COPD patients and determined their outcomes. Methods We phenotyped 72 sputum samples of COPD patients who were hospitalized with a primary diagnosis of AECOPD using a molecular array that detected common bacterial and viral respiratory pathogens. Based on these results, the patients were classified into positive or negative pathogen groups. The pathogen-positive group was further divided into virus or bacteria subgroups. Admission day 1 blood samples were assayed for N-terminal prohormone brain natriuretic peptide, CRP, and complete blood counts. Results A total of 52 patients had a positive result on the array, while 20 patients had no pathogens detected. The most common bacterial pathogen detected was Haemophilus influenzae and the most common virus was rhinovirus. The pathogen-negative group had the worse outcomes with longer hospital stays (median 6.5 vs 5 days for bacteria-positive group, P=0.02) and a trend toward increased 1-year mortality (P=0.052). The bacteria-positive group had the best prognosis, whereas the virus-positive group had outcomes somewhere in between the bacteria-positive and pathogen-negative groups. Conclusion Molecular diagnostics on sputum can rapidly phenotype serious AECOPD into bacteria-, virus-, or pathogen-negative groups. The bacteria-positive group appears to have the best prognosis, while pathogen-negative group has the worst. These data suggest that AECOPD is a heterogeneous event and that accurate phenotyping of AECOPD may lead to novel management strategies that are personalized and more precise.

Background: Quantifying age trends in healthcare costs of pediatric asthma leads to better understanding of the natural history of the disease and informed decision-making on the allocation of healthcare resources. Methods: We identified children with incident asthma from the health administrative data of British Columbia, Canada (Jan 1998 to Dec 2015), and followed them from their first diagnosis of asthma or wheezing until age 18. We estimated direct medical costs (in 2016 Canadian dollars [$]), including inpatient and outpatient encounters and pharmacy costs, attributed to asthma (primary outcome) and other respiratory diseases (secondary outcome). We assessed the impact of sex and socioeconomic status on age trends, adjusting for calendar effect. Results: The final analysis included 44,552 children with asthma (62% boys). From age 0 to 18, costs of asthma/wheezing and other respiratory conditions decreased from $1,036 to $29/child-year, and from $1,145 to $31/child-year, respectively. Children under 3 years of age incurred 4–fold higher costs for asthma/wheezing and other respiratory conditions. In particular, costs of asthma hospitalizations were 10 times higher in this age group compared to older children. Age trends were generally similar between sex groups and across socioeconomic status. However, medication costs for asthma/wheezing decreased in boys, whereas those in girls declined during childhood but increased during adolescence. Conclusions: The highest costs of pediatric asthma are concentrated in children younger than 3. Age trends were generally consistent between sex and across socioeconomic status.

Tiotropium Respimat is an efficacious add-on to maintenance treatment in patients with symptomatic asthma. Currently, the Global Initiative for Asthma (GINA) strategy recommends tiotropium for patients at Steps 4–5. To assess the clinical benefits of tiotropium Respimat across asthma severities, GINA Steps 2–5, a post hoc analysis of five double-blind trials (12–48-weeks; patients aged 18–75 years) investigated the effect of tiotropium Respimat, 5 μg or 2.5 μg, versus placebo, on peak forced expiratory volume in 1 s (FEV1) within 3 h post-dose (FEV1(0–3h)) response, and Asthma Control Questionnaire-7 (ACQ-7) responder rate. GINA step grouping was based on patients’ background treatment regimen. Baseline characteristics of patients (N = 2926) were balanced between treatments. Tiotropium Respimat showed consistent improvements in lung function across GINA steps; placebo-corrected peak FEV1(0–3h) improvements after tiotropium Respimat 5 μg and 2.5 μg were: Step 2 (Week 8), 135 mL (95% confidence interval: 84, 187) and 155 mL (103, 206); Step 3 (Week 24), 187 mL (139, 235) and 235 mL (187, 283); Step 4 (Week 24), 111 mL (63, 159) and 181 mL (35, 326); Step 5 (Week 24; 5 μg only), 164 mL (5, 323). Asthma control improved with tiotropium Respimat versus placebo, showing statistical significance (nominal P value) with tiotropium Respimat 5 μg at Step 4 (odds ratio 1.36 [1.03, 1.78]). Safety profiles were similar between treatments. In conclusion, tiotropium Respimat add-on therapy improves lung function, and may improve asthma control, in adults across disease severities.

Background CCR3 is the cognate receptor for major human eosinophil chemoattractants from the eotaxin family of proteins that are elevated in asthma and correlate with disease severity. Objective This proof-of-mechanism study examined the effect of AXP1275, an oral, small-molecule inhibitor of CCR3, on airway responses to inhaled allergen challenge. Methods Twenty-one subjects with mild atopic asthma and documented early and late asthmatic responses to an inhaled aeroallergen completed a randomized double-blind cross-over study to compare early and late allergen-induced asthmatic responses, methacholine PC20 , blood and sputum eosinophils and exhaled nitric oxide after 2 weeks of treatment with once-daily doses of AXP1275 (50 mg) or placebo. Results There was a significant increase in methacholine PC20 after 12 days of AXP1275 treatment compared to placebo (increase of 0.92 doubling doses versus 0.17 doubling doses, P = .01), but this protection was lost post-allergen challenge. There was no effect of AXP1275 on allergen-induced late asthmatic responses, or eosinophils in blood and sputum. The early asthmatic response and exhaled nitric oxide levels were slightly lower with AXP1275, but this did not reach statistical significance. The number of subjects who experienced treatment-emergent adverse events while receiving AXP1275 was comparable placebo. Conclusions & clinical relevance AXP1275 50 mg administered daily was safe and well tolerated, and there was no difference in the type, severity or frequency of treatment-emergent adverse events in subjects while receiving AXP1275 compared to placebo. AXP1275 increased the methacholine PC20 ; however, the low and variable exposure to APX1275 over a short treatment period may have contributed to poor efficacy on other outcomes.

Purpose There has been limited research on the role of peer support in self-management for patients with chronic obstructive pulmonary disease (COPD) attending pulmonary rehabilitation (PR) programs. This research explored patient acceptability of "peer supporters" in promoting sustained self-management practices after PR and to assess their perceived self-efficacy to manage their disease. Methods This qualitative study used focus groups and individual interviews to identify perspectives of peer supporters and benefits of participation in a PR program. The analysis included systematically reading and reviewing transcripts of the sessions, establishing themes, and sorting responses into thematic categories. Results A total of 28 patients with COPD (15 males) participated in either a focus group or interview. The majority of participants considered peer supporters to be good facilitators for motivating ongoing exercise after completing PR. Exercise sessions were viewed as extremely beneficial for disease management, and many were satisfied with the care they had received. Most subjects wanted to receive followup sessions with either a professional or peer after the intensive phase of PR. Overall, the concept of having a peer supporter involved in ongoing maintenance of self-management efforts after PR was generally viewed as positive. Conclusions Integrating a peer support model into PR programs may improve better long-term health outcomes for COPD management as many participants endorsed the need for continued support after the program. It also improved our understanding of the role of "peer supports" in exercise and self-care maintenance after PR. The selection of peers and the specific model used warrants further investigation in a randomized controlled trial.

BackgroundAsthma diagnosis in the community is often made without objective testing.ObjectiveThe aim of this study was to evaluate the cost-effectiveness of implementing a stepwise objective diagnostic verification algorithm among patients with community-diagnosed asthma in the United States (US).MethodsWe developed a probabilistic time-in-state cohort model that compared a stepwise asthma verification algorithm based on spirometry and methacholine challenge test against the current standard of care over 20 years. Model input parameters were informed from the literature and with original data analyses when required. The target population was US adults (≥15 y/o) with physician-diagnosed asthma. The final outcomes were costs (in 2018 $) and quality-adjusted life years (QALYs), discounted at 3% annually. Deterministic and probabilistic analyses were undertaken to examine the effect of alternative assumptions and uncertainty in model parameters on the results.ResultsIn a simulated cohort of 10,000 adults with diagnosed asthma, the stepwise algorithm resulted in the removal of diagnosis in 3,366. This was projected to be associated with savings of $36.26 million in direct costs and a gain of 4,049.28 QALYs over 20 years. Extrapolating these results to the US population indicated an undiscounted potential savings of $56.48 billion over 20 years. Results were robust against alternative assumptions and plausible changes in values of input parameters.ConclusionImplementation of a simple diagnostic testing algorithm to verify asthma diagnosis might result in substantial savings and improvement in patients’ quality of life.Key MessagesCompared with current standards of practice, the implementation of an asthma verification algorithm among US adults with diagnosed asthma can be associated with reduction in costs and gain in quality of life.There is substantial room for improving patient care and outcomes through promoting objective asthma diagnosis.Capsule summaryAsthma ‘overdiagnosis’ is common among US adults. An objective, stepwise verification algorithm for re-evaluation of asthma diagnosis can result in substantial savings in costs and improvements in quality of life.

Introduction We performed a comprehensive assessment of the effect of tiotropium Respimat® add-on therapy on episodes of asthma worsening in adult patients with symptomatic asthma despite inhaled corticosteroid (ICS)/long-acting beta2-agonist (LABA) treatment. Methods The PrimoTinA-asthma® studies (NCT00772538/NCT00776984) were two replicate 48 week, Phase III trials, which, when pooled, were powered to investigate the effect of tiotropium Respimat®5 µg (as two puffs once daily) or placebo on episodes of asthma worsening and exacerbations when added onto ICS ≥800 µg budesonide equivalent/day+LABA± additional controller medication. Endpoints included time to first episode of asthma worsening during the 48 week treatment period – defined as either a progressive increase in symptoms (as compared with usual day-to-day asthma symptoms) or a decline of ≥30% in morning peak expiratory flow for ≥2 consecutive days – and number of episodes of asthma worsening per patient. Time to first asthma worsening was also analysed by baseline patient characteristics, and number of episodes was analysed by month in order to determine any seasonality effect. Results In pooled data from the two studies (n=912), time to first asthma worsening was longer in the tiotropium group compared with placebo, with a 31% risk reduction (hazard ratio 0.69; 95% confidence interval [CI] 0.58, 0.82; p Conclusion Tiotropium Respimat® add-on therapy reduced the rate of episodes of asthma worsening in adults with symptomatic severe asthma, irrespective of several baseline characteristics, allergic characteristics, and across seasons, including the autumn peak. This comprehensive assessment of the effect of tiotropium on asthma worsening in PrimoTinA-asthma® broadens the evidence supporting the use of tiotropium as add-on therapy in patients with symptomatic asthma despite ICS/LABA therapy. Please refer to page A265 for declarations of interest related to this abstract.

Introduction There is little information on recent trends in the economic burden of asthma. Our objective was to estimate the excess costs of asthma and their trend in British Columbia, Canada, from 2002 to 2011. Methods A retrospective cohort of individuals aged 5–55 years was constructed from the provincial administrative health databases, consisting of patients with physician-diagnosed asthma and a propensity-score-matched comparison sample from the general population. Total direct medical costs were calculated as the sum of hospitalizations, outpatient visits and medication costs, adjusted to 2012 Canadian dollars ($). Excess costs were defined as the difference in costs between the asthma and comparison groups. Results A total of 341 457 individuals (mean age at entry 27.3, 54.1% female) were equally divided into the asthma and comparison groups. Excess costs in patients with asthma were $1028.0 (95% CI $982.7–$1073.4) per patient-year (PY). Medications contributed to the greatest share of excess costs ($471.7/PY), whereas hospitalization and outpatient costs were, respectively, $272.2/PY and $284.1/PY. Only $192.9/PY was attributable to asthma itself. There was a 2.9%/year increase in excess costs (P < 0.001), a combination of asthma-attributable costs declining by 0.8%/year while nonasthma excess costs increasing by 3.8%/year. The most dramatic trend was observed in asthma-related outpatient costs, which decreased by %6.6/year. Conclusions A significant share of excess costs in asthma is not attributable to the disease itself. The pattern of costs changed significantly during the study period. The burden of comorbid conditions should be considered in developing evidence-based policies for management of patients with asthma.

Iraj Poureslami,1,2 Susan Kwan,3 Stephen Lam,4,5 Nadia A Khan,6,7 JohnMarkFitzGerald8,9 1Respiratory Division, Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, Canada; 2Department of Graduate Studies, Centre for Clinical Epidemiology and Evaluation, Vancouver Coastal Health Research Institute, Vancouver, Canada; 3Respiratory Department, Burnaby Hospital, University of British Columbia, Burnaby, Canada; 4Respiratory Division, University of British Columbia, Vancouver, Canada; 5Department of Integrative Oncology, BC Cancer Research Centre, Vancouver, Canada; 6Department of Internal Medicine, Faculty of Medicine, University of British Columbia, Vancouver, Canada; 7Department of Internal Medicine, Providence Health Care Authority, Vancouver, Canada; 8VGH Divisions of Respiratory Medicine, University of British Columbia, Vancouver, Canada; 9Respiratory Medicine, Vancouver Coastal Health Authority, Vancouver Coastal Health Research Institute, Institute for Heart and Lung Health, The Lung Centre, Gordon and Leslie Diamond Health Care Centre, Vancouver, Canada Background: Patient education is a key component in the management of chronic obstructive pulmonary disease (COPD). Delivering effective education to ethnic groups with COPD is a challenge. The objective of this study was to develop and assess the effectiveness of culturally and linguistically specific audiovisual educational materials in supporting self-management practices in Mandarin- and Cantonese-speaking patients. Methods: Educational materials were developed using participatory approach (patients involved in the development and pilot test of educational materials), followed by a randomized controlled trial that assigned 91 patients to three intervention groups with audiovisual educational interventions and one control group (pamphlet). The patients were recruited from outpatient clinics. The primary outcomes were improved inhaler technique and perceived self-efficacy to manage COPD. The secondary outcome was improved patient understanding of pulmonary rehabilitation procedures. Results: Subjects in all three intervention groups, compared with control subjects, demonstrated postintervention improvements in inhaler technique (P

Background Asthma control is increasingly used as an outcome measure in asthma trials. Economic evaluations of asthma interventions require converting the impact of interventions on control to impact on resource use. The purpose of this study was to estimate the savings in direct costs by achieving asthma symptom control as defined in the Global Initiative for Asthma (GINA) 2014 management strategy. Methods Adolescents and adults with asthma were recruited through random digit dialing. Asthma control per GINA and the use of healthcare resources were assessed at baseline and three-monthly visits up to 1 year. We used regression models to associate costs, measured in 2012 Canadian dollars ($), with symptom control, adjusting for potential confounding variables. Results The final sample included 517 individuals (average age 48.9, 65.8% female) with mostly mild–moderate asthma contributing 2033 follow-up visits. In 598 (29.4%), 809 (39.8%), and 626 (30.8%) of visits, asthma was symptomatically controlled, partially controlled, or uncontrolled, respectively. The average 3-month costs of asthma were $134.5. Of these, 20.5% were attributable to inpatient care, 47.8% to outpatient care, and 31.5% to medication. Compared to controlled asthma, partially controlled asthma was associated with a nonsignificant increase of $9.5 (95% CI -$13.6 – $32.6) in adjusted 3-month costs and uncontrolled asthma with a statistically significant increase of $81.7 (95% CI $48.5 – $114.9). Conclusion A substantial fraction of this population-based sample of largely mild–moderate asthmatics was symptomatically uncontrolled. Achieving symptom control was associated with a reduction in direct costs. The adjusted values from this study can be used to inform cost-effectiveness analyses of asthma treatments.

Background: Dupilumab (DPL), a fully human anti-IL-4Rα mAb that inhibits IL-4/IL-13, is approved for treatment of adults with inadequately controlled moderate-to-severe atopic dermatitis. DPL previously suppressed type 2 inflammatory biomarkers during 24 weeks of treatment (NCT01854047). In a phase 3 study (NCT02414854), asthma patients (pts) aged ≥12 years, with no minimum baseline (BL) eosinophil requirement, uncontrolled with medium-to-high-dose ICS, plus 1 or 2 controllers received DPL 200/300mg or placebo (PBO) every 2 weeks for 52 weeks. DPL reduced severe asthma exacerbations, improved FEV1 and quality of life measures, and was generally well tolerated. Aim: Report effect of DPL on pharmacodynamic (PD) parameters. Methods: PD parameters: change from BL in FeNO, eotaxin-3, total IgE, periostin and TARC at Weeks 12 and 52. Results: BL biomarker values were elevated and comparable in all groups (Table). Pts receiving DPL demonstrated a statistically significant decrease in biomarkers concomitant with efficacy. A near-maximal effect was observed by Week 12 and sustained over the 52-week treatment period. Most common AE, with higher frequency in 200/300mg DPL vs PBO, was injection-site reactions (21%/24% vs 6%/14%). Conclusion: DPL showed rapid and sustained suppression of systemic and airway type 2 inflammatory biomarkers (including FeNO and IgE) in asthma pts, and was generally well tolerated.

Abdulmajeed Alshabanat,1 Michael C Otterstatter,2,3 Don D Sin,4,5 Jeremy Road,5,6 Carmen Rempel,6 Jane Burns,6 Stephan F van Eeden,4,5 JM FitzGerald5–7 On behalf of the COPD Transition Team Program 1Department of Experimental Medicine, University of British Columbia, 2British Columbia Centre for Disease Control, 3School of Population and Public Health, 4Department of Medicine, Centre for Heart Lung Innovation, St Paul’s Hospital, 5Division of Respirology, Department of Medicine, 6Department of Medicine, Faculty of Medicine, Institute for Heart and Lung Health, University of British Columbia, 7Centre for Clinical Epidemiology and Evaluation, Vancouver Coastal Health Institute, Vancouver, BC, Canada Background: COPD accounts for the highest rate of hospital admissions among major chronic diseases. COPD hospitalizations are associated with impaired quality of life, high health care utilization, and poor prognosis and result in an economic and a social burden that is both substantial and increasing.Aim: The aim of this study is to determine the efficacy of a comprehensive case management program (CCMP) in reducing length of stay (LOS) and risk of hospital admissions and readmissions in patients with COPD.Materials and methodology: We retrospectively compared outcomes across five large hospitals in Vancouver, BC, Canada, following the implementation of a systems approach to the management of COPD patients who were identified in the hospital and followed up in the community for 90days. We compared numbers, rates, and intervals of readmission and LOS during 2years of active program delivery compared to 1year prior to program implementation.Results: A total of 1,564 patients with a clinical diagnosis of COPD were identified from 2,719 hospital admissions during the 3years of study. The disease management program reduced COPD-related hospitalizations by 30% and hospitalizations for all causes by 13.6%. Similarly, the rate of readmission for all causes showed a significant decline, with hazard ratios (HRs) of 0.55 (year 1) and 0.51 (year 2) of intervention (P

Introduction Dans l’asthme leger, budesonide/formoterol (BUD/FORM) a la demande (PRN, pro re nata) diminue le risque d’exacerbations severes comparativement au bras terbutaline (TER) PRN, diminution comparable par rapport au bras BUD en traitement de fond + TER PRN [1] . Dans une analyse post-hoc de l’etude SYGMA 1 ( NCT02149199 ), le risque a court terme d’une exacerbation severe a ete etudie apres differents niveaux d’utilisation du traitement de secours sur une journee, comparant le bras BUD/FORM PRN par rapport aux bras TER PRN avec ou sans BUD en traitement de fond. Methodes Randomisation de 3 836 patients presentant un asthme leger ; 3 bras : placebo deux fois par jour (bid) + TER 0,5 mg PRN, placebo bid + BUD/FORM 200/6 μg PRN ou traitement de fond par BUD 200 μg bid + TER PRN. Les proportions de patients ayant pris > 2, > 4, > 6 ou > 8 inhalations de traitement de secours quel que soit le jour de l’etude, avec une exacerbation au cours des 21 jours suivants ont ete comparees. Resultats Les proportions de patients presentant des jours avec une utilisation > 4, > 6 ou > 8 inhalations a la demande ont ete inferieures dans le bras BUD/FORM PRN par rapport aux bras TER PRN avec ou sans BUD traitement de fond, avec une diminution du risque d’exacerbation severe au cours des 21 jours suivants par rapport au bras TER PRN. La tolerance du traitement par BUD/FORM PRN a ete similaire dans tous les groupes. Conclusion Dans l’asthme leger, le traitement de secours anti-inflammatoire par BUD/FORM a la demande diminue le nombre de jours avec une utilisation importante de traitement de secours (> 4 inhalations) et diminue les exacerbations au cours des 21 jours suivants la prise par rapport au bras TER PRN.

Setting Tuberculosis (TB) in-patient treatment unit in Vancouver, Canada. Objective To examine the results of therapeutic drug monitoring (TDM) in anti-tuberculosis treatment. Design We performed a retrospective analysis of TDM data from 2000 to 2010. All in-patients treated for TB with TDM performed during their treatment course were included. Results TDM was performed on 52 patients in 76 treatment episodes from 2000 to 2010. Overall, 103/213 (48.4%) drug levels measured were low, and 5/213 (2.3%) were high. At least one drug level was low in 47/52 (90.3%) patients. Initial serum levels were low in respectively 76.6% and 68.4% of isoniazid (INH) and rifampicin (RMP) levels. In contrast, only 2.9% of initial pyrazinamide levels were low. Five patients with a susceptible strain on initial presentation later developed drug-resistant disease, with all five patients demonstrating at least one low drug level and two demonstrating multiple low levels. Dose adjustments were made in response to 26 INH and RMP levels, with variable serum responses. Conclusion In this population with high rates of treatment failure and acquired resistance, we demonstrate that most patients had low drug levels. Prospective studies are required to examine the relationship between drug levels and clinical outcomes.

BACKGROUND: Asthma is a biologically heterogeneous disease and development of novel therapeutics requires understanding of pathophysiologic phenotypes. There is uncertainty regarding the stability of clinical characteristics and biomarkers in asthma over time. This report presents the longitudinal stability over 12 months of clinical characteristics and clinically accessible biomarkers from ADEPT.METHODS: Mild, moderate, and severe asthma subjects were assessed at 5 visits over 12 months. Assessments included patient questionnaires, spirometry, bronchodilator reversibility, fractional exhaled nitric oxide (FENO), and biomarkers measured in induced sputum.RESULTS: Mild (n = 52), moderate (n = 55), and severe (n = 51) asthma cohorts were enrolled from North America and Western Europe. For all clinical characteristics and biomarkers, group mean data showed no significant change from visit to visit. However, individual data showed considerable variability. FEV1/FVC ratio showed excellent reproducibility while pre-bronchodilator FEV1 and FVC were only moderately reproducible. Of note bronchodilator FEV1 reversibility showed low reproducibility, with the nonreversible phenotype much more reproducible than the reversible phenotype. The 7-item asthma control questionnaire (ACQ7) demonstrated moderate reproducibility for the combined asthma cohorts, but the uncontrolled asthma phenotype (ACQ7 > 1.5) was inconstant in mild and moderate asthma but stable in severe asthma. FENO demonstrated good reproducibility, with the FENO-low phenotype (FENO CONCLUSIONS: The ADEPT cohort showed group stability, individual stability in some parameters e.g. low FEV1/FVC ratio, and low FENO, but marked individual variability in other clinical characteristics and biomarkers e.g. type-2 biomarkers over 12 months. This variability is possibly related to seasonal variations in climate and allergen exposure, medication changes and acute exacerbations. The implications for patient selection strategies based on clinical biomarkers may be considerable.

The aim of the present study was to compare the effectiveness, safety and health economics of budesonide/formoterol maintenance and a novel reliever therapy with conventional best practice in patients with persistent asthma in Canada. After 2 weeks of usual therapy, 1,538 patients were randomised for 6 months to open-label budesonide/formoterol maintenance and reliever therapy 160/4.5 microg twice daily and as needed, or to guideline-based conventional best practice. Severe asthma exacerbations, reliever medication use and total inhaled corticosteroid dose were analysed in all patients and airway inflammation was assessed in a sub-study of 115 patients. No differences were seen in time to first severe exacerbation and severe asthma exacerbation rate. There were numerically fewer emergency room visits or hospitalisations with budesonide/formoterol maintenance and reliever therapy (4.4 versus 7.5 events per 100 patients x yr(-1), 41% reduction); however, this did not reach statistical significance. Mean total inhaled corticosteroid dose, reliever use, asthma medication costs and total annual costs per patient were all significantly lower with budesonide/formoterol maintenance and reliever therapy. Mean sputum eosinophil cell counts remained in the range for controlled inflammation in both groups. In conclusion, budesonide/formoterol maintenance and reliever therapy achieved similar or improved clinical control compared with conventional best practice, with significantly lower total inhaled corticosteroid dose and lower cost, while maintaining similar control of eosinophilic inflammation.

BACKGROUND: Obstructive sleep apnea-hypopnea (OSAH) is a common disorder characterized by recurrent collapse of the upper airway during sleep. Patients experience a reduced quality of life and an increased risk of motor vehicle crashes (MVCs). Continuous positive airway pressure (CPAP), which is the first-line therapy for OSAH, improves sleepiness, vigilance and quality of life.OBJECTIVE: To assess the cost-effectiveness of CPAP therapy versus no treatment for OSAH patients who are drivers.METHODS: A Markov decision analytical model with a five-year time horizon was used. The study population consisted of male and female patients, between 30 and 59 years of age, who were newly diagnosed with moderate to severe OSAH. The model evaluated the cost-effectiveness of CPAP therapy in reducing rates of MVCs and improving quality of life. Utility values were obtained from previously published studies. Rates of MVCs under the CPAP and no CPAP scenarios were calculated from Insurance Corporation of British Columbia data and a systematic review of published studies. MVCs, equipment and physician costs were obtained from the British Columbia Medical Association, published cost-of-illness studies and the price lists of established vendors of CPAP equipment in British Columbia. Findings were examined from the perspectives of a third-party payer and society.RESULTS: From the third-party payer perspective, CPAP therapy was more effective but more costly than no CPAP (incremental cost-effectiveness ratio [ICER] of $3,626 per quality-adjusted life year). From the societal perspective, the ICER was similar ($2,979 per quality-adjusted life year). The ICER was most dependent on preference elicitation method used to obtain utility values, varying almost sixfold under alternative assumptions from the base-case analysis.CONCLUSION: After considering costs and impact on quality of life, as well as the risk of MVCs in individuals with OSAH, CPAP therapy for OSAH patients is a highly efficient use of health care resources. Provincial governments who do not provide funding for CPAP therapy should reconsider.

OBJECTIVE: To evaluate the prevalence of gastroesophageal reflux disease (GERD) in patients presenting with asthma and chronic cough.PATIENTS AND METHODS: The charts of 358 consecutive patients who were referred for ambulatory gastroesophageal pH monitoring to the Lung Centre in Vancouver, British Columbia, were reviewed, and the data of 108 (30%) patients with asthma and 134 (37%) patients with chronic cough were analyzed. The maintenance treatment for GERD was discontinued before patients underwent the pH monitoring study. One hundred eighteen (33%) patients were excluded.RESULTS: Reflux episodes identified reflux events as the percentage of time where the pH was less than four. For asthma patients, 70 (64.8%) had distal total reflux, 50 (46.3%) had distal upright reflux, 41 (38.3%) had distal supine reflux and 73 (67.6%) had other distal refluxes. Proximal total reflux in asthmatic patients was present in 56 (52%), proximal upright reflux in 55 (51%) and proximal supine reflux in 56 (52%) patients. For chronic cough patients, 70 (52.6%) had distal total reflux, 59 (44.4%) had distal upright reflux, 45 (34.4%) had distal supine reflux and 75 (56%) patients had other distal refluxes. In chronic cough patients, proximal total reflux was present in 70 (52%), proximal upright reflux in 80 (60%) and proximal supine reflux in 59 (44%). Presenting respiratory and/or reflux symptoms were absent in approximately 25% of patients with asthma and reflux, and in approximately 50% of patients with chronic cough and reflux. During pH monitoring, symptoms did not differ significantly between those with and without distal reflux in both study groups, except for more significant heartburn in patients with chronic cough and reflux (RR 2.0).CONCLUSIONS: The data of the present study support the observation that there is a high prevalence of GERD in patients with asthma or chronic cough. The use of different pH parameters for detecting acid reflux during 24 h ambulatory pH monitoring, such as proximal esophageal acid measurement, should be considered as part of the routine interpretation of such testing. A low threshold for diagnosing GERD in patients with asthma or chronic cough is essential, because respiratory and/or reflux symptoms can be absent or atypical in some of these patients.

BACKGROUND:The lack of a relationship between airway responsiveness and respiratory symptoms in epidemiological studies of children may, in part, reflect inaccuracies in symptom reporting or inadequate knowledge by the parent of the child's symptoms.OBJECTIVE:To relate airway responsiveness to methacholine in children with symptoms of respiratory illness in the child as reported by the parent and as reported by the child.POPULATION:Eight- to 10-year-old (n=290) randomly sampled schoolchildren.SETTING:Seven randomly selected schools in Ontario.METHODS:Parents completed a mailed questionnaire regarding the child's respiratory health. Children completed a similar interview-administered questionnaire at school and underwent methacholine challenge testing by the tidal breathing method.RESULTS:The cumulative prevalence of a history of physician-diagnosed asthma was 9.0%, and of any wheezing it was 25.5%. A further 9% of children reported wheezing not documented by their parent. Of 229 children consenting to methacholine challenge, 78 (34.1%) showed airway responsiveness in the range generally associated with asthma in adults (provocation concentration of methacholine causing a 20% fall [PC20] in forced expired volume in 1 s [FEV1] 8 mg/mL or less); half of these children had no history of respiratory symptoms reported by the parent. The sensitivity of airway hyperresponsiveness defined by a cut-point for PC208 mg/mL or less in relation to any history of recurrent wheezing reported by the parent was 48% and did not improve if only symptoms within the past year were considered (sensitivity 44%); the specificity of the test for parent-reported symptoms ever was 71%, and 68% in those with symptoms in the past year. None of these sensitivities or specificities was increased by using symptoms reported by the child or by combining parent and child reported symptoms. Receiver operating characteristic (ROC) curves for sensitivity and specificity of the methacholine test were constructed for parent and child reports of symptoms. For all symptom strata, the cut-point of PC20producing optimal balance of sensitivity and specificity was between 4 and 8 mg/mL. A parental questionnaire positive for physician-diagnosed asthma was strongly related to methacholine response, producing an ROC curve with an area significantly different from 0.5 (P=0.006), as did all parent-reported wheezing (P=0.009). If the child reported asthma, there was an equally strong relationship, with a positive ROC curve (P=0.001), as there was for all child-reported wheezing (P=0.048).CONCLUSIONS:Airway hyperresponsiveness to methacholine in children relates closely with asthma and wheezing reported by either the parent or the child. In addition, the results confirm that respiratory symptoms and airway hyperresponsiveness are common in Canadian children, and that airway hyperresponsiveness may be found in children with no history of respiratory illness either at present or in the past.