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© 2016 Leung et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.B

Background: The purpose of this randomised double-blind double-dummy placebo-controlled trial was to investigate whether etanercept, a tumour necrosis factor α (TNFα) antagonist, would provide more effective anti-inflammatory treatment for acute exacerbations of chronic obstructive pulmonary disease (COPD) than prednisone.Methods: We enrolled 81 patients with acute exacerbations of COPD and randomly assigned them to treatment with either 40 mg oral prednisone given daily for 10 days or to 50 mg etanercept given subcutaneously at randomisation and 1 week later. Both groups received levofloxacin for 10 days plus inhaled bronchodilators. The primary endpoint was the change in the patient's forced expiratory volume in 1 s (FEV(1)) 14 days after randomisation. Secondary endpoints included 90-day treatment failure rates and dyspnoea and quality of life.Results: At 14 days the mean±SE change in FEV(1) from baseline was 20.1±5.0% and 15.2±5.7% for the prednisone and etanercept groups, respectively. The mean between-treatment difference was 4.9% (95% CI -10.3% to 20.2%), p=0.52. Rates of treatment failure at 90 days were similar in the prednisone and etanercept groups (32% vs 40%, p=0.44), as were measures of dyspnoea and quality of life. Subgroup analysis revealed that patients with serum eosinophils >2% at exacerbation tended to experience fewer treatment failures if treated with prednisone compared with etanercept (22% vs 50%, p=0.08).Conclusions: Etanercept was not more effective than prednisone for treatment of acute exacerbations of COPD. Efficacy of prednisone was most apparent in patients who presented with serum eosinophils >2%.Clinical Trials: gov number NCT 00789997. [ABSTRACT FROM AUTHOR]

RATIONALE: We developed an evidence-based decision aid for patients with advanced cystic fibrosis considering referral for lung transplantation. OBJECTIVES: To prospectively evaluate whether use of the decision aid increased knowledge about the options, improved realistic expectations, and decreased decisional conflict in adult patients. METHODS: We performed a single-blind randomized controlled trial involving 149 adult patients with cystic fibrosis with an FEV(1)

Background: It is unclear whether asthma is overdiagnosed in developed countries, particularly among obese individuals, who may be more likely than nonobese people to experience dyspnea.Methods: We conducted a longitudinal study involving nonobese (body mass index 20-25) and obese (body mass index >/= 30) individuals with asthma that had been diagnosed by a physician. Participants were recruited from 8 Canadian cities by means of random-digit dialing. A diagnosis of current asthma was excluded in those who did not have evidence of acute worsening of asthma symptoms, reversible airflow obstruction or bronchial hyperresponsiveness, despite being weaned off asthma medications. We stopped asthma medications in those in whom a diagnosis of asthma was excluded and assessed their clinical outcomes over 6 months.Results: Of 540 individuals with physician-diagnosed asthma who participated in the study, 496 (242 obese and 254 nonobese) could be conclusively assessed for a diagnosis of asthma. Asthma was ultimately excluded in 31.8% (95% confidence interval [CI] 26.3%-37.9%) in the obese group and in 28.7% (95% CI 23.5%-34.6%) in the nonobese group. Overdiagnosis of asthma was no more likely to occur among obese individuals than among nonobese individuals (p = 0.46). Of those in whom asthma was excluded, 65.5% did not need to take asthma medication or seek health care services because of asthma symptoms during a 6-month follow-up period.Interpretation: About one-third of obese and nonobese individuals with physician-diagnosed asthma did not have asthma when objectively assessed. This finding suggests that, in developed countries such as Canada, asthma is overdiagnosed. [ABSTRACT FROM AUTHOR]

Background: Treatment of moderate or severe chronic obstructive pulmonary disease (COPD) with combinations of inhaled corticosteroids, long-acting beta-agonists, and long-acting anticholinergic bronchodilators is common but unstudied.Objective: To determine whether combining tiotropium with salmeterol or fluticasone-salmeterol improves clinical outcomes in adults with moderate to severe COPD compared with tiotropium alone.Design: Randomized, double-blind, placebo-controlled trial conducted from October 2003 to January 2006.Setting: 27 academic and community medical centers in Canada.Patients: 449 patients with moderate or severe COPD.Intervention: 1 year of treatment with tiotropium plus placebo, tiotropium plus salmeterol, or tiotropium plus fluticasone-salmeterol.Measurements: The primary end point was the proportion of patients who experienced an exacerbation of COPD that required treatment with systemic steroids or antibiotics.Results: The proportion of patients in the tiotropium plus placebo group who experienced an exacerbation (62.8%) did not differ from that in the tiotropium plus salmeterol group (64.8%; difference, -2.0 percentage points [95% CI, -12.8 to 8.8 percentage points]) or in the tiotropium plus fluticasone-salmeterol group (60.0%; difference, 2.8 percentage points [CI, -8.2 to 13.8 percentage points]). In sensitivity analyses, the point estimates and 95% confidence bounds shifted in the direction favoring tiotropium plus salmeterol and tiotropium plus fluticasone-salmeterol. Tiotropium plus fluticasone-salmeterol improved lung function (P = 0.049) and disease-specific quality of life (P = 0.01) and reduced the number of hospitalizations for COPD exacerbation (incidence rate ratio, 0.53 [CI, 0.33 to 0.86]) and all-cause hospitalizations (incidence rate ratio, 0.67 [CI, 0.45 to 0.99]) compared with tiotropium plus placebo. In contrast, tiotropium plus salmeterol did not statistically improve lung function or hospitalization rates compared with tiotropium plus placebo.Limitations: More than 40% of patients who received tiotropium plus placebo and tiotropium plus salmeterol discontinued therapy prematurely, and many crossed over to treatment with open-label inhaled steroids or long-acting beta-agonists.Conclusions: Addition of fluticasone-salmeterol to tiotropium therapy did not statistically influence rates of COPD exacerbation but did improve lung function, quality of life, and hospitalization rates in patients with moderate to severe COPD. International Standard Randomised Controlled Trial registration number: ISRCTN29870041. [ABSTRACT FROM AUTHOR]

Context: High levels of variation and inefficiency exist in current clinical practice regarding use of cervical spine (C-spine) radiography in alert and stable trauma patients.Objective: To derive a clinical decision rule that is highly sensitive for detecting acute C-spine injury and will allow emergency department (ED) physicians to be more selective in use of radiography in alert and stable trauma patients.Design: Prospective cohort study conducted from October 1996 to April 1999, in which physicians evaluated patients for 20 standardized clinical findings prior to radiography. In some cases, a second physician performed independent interobserver assessments.Setting: Ten EDs in large Canadian community and university hospitals.Patients: Convenience sample of 8924 adults (mean age, 37 years) who presented to the ED with blunt trauma to the head/neck, stable vital signs, and a Glasgow Coma Scale score of 15.Main Outcome Measure: Clinically important C-spine injury, evaluated by plain radiography, computed tomography, and a structured follow-up telephone interview. The clinical decision rule was derived using the kappa coefficient, logistic regression analysis, and chi(2) recursive partitioning techniques.Results: Among the study sample, 151 (1.7%) had important C-spine injury. The resultant model and final Canadian C-Spine Rule comprises 3 main questions: (1) is there any high-risk factor present that mandates radiography (ie, age >/=65 years, dangerous mechanism, or paresthesias in extremities)? (2) is there any low-risk factor present that allows safe assessment of range of motion (ie, simple rear-end motor vehicle collision, sitting position in ED, ambulatory at any time since injury, delayed onset of neck pain, or absence of midline C-spine tenderness)? and (3) is the patient able to actively rotate neck 45 degrees to the left and right? By cross-validation, this rule had 100% sensitivity (95% confidence interval [CI], 98%-100%) and 42.5% specificity (95% CI, 40%-44%) for identifying 151 clinically important C-spine injuries. The potential radiography ordering rate would be 58.2%.Conclusion: We have derived the Canadian C-Spine Rule, a highly sensitive decision rule for use of C-spine radiography in alert and stable trauma patients. If prospectively validated in other cohorts, this rule has the potential to significantly reduce practice variation and inefficiency in ED use of C-spine radiography. [ABSTRACT FROM AUTHOR]

Obstructive airway disease is associated with sleep disturbances. We aimed to assess the relationship between lung function and sleep disorder symptoms using cross-sectionally collected data between March 2017 and August 2021 from the Undiagnosed Chronic Obstructive Pulmonary Disease and Asthma Population study, a prospective community-based multi-site case-finding study. Undiagnosed Chronic Obstructive Pulmonary Disease and Asthma Population study participants with respiratory symptoms but without diagnosed lung disease who completed spirometry and the Global Sleep Assessment Questionnaire were included. We conducted multivariate linear regression models for forced expiratory volume in 1 s, forced vital capacity and forced expiratory volume in 1 s/forced vital capacity by Global Sleep Assessment Questionnaire responses adjusted for confounders. The same models were employed to examine respiratory symptoms, as reported on the St George's Respiratory Questionnaire and Chronic Obstructive Pulmonary Disease Assessment Test, by Global Sleep Assessment Questionnaire responses. Logistic regression models were used to assess the association of undiagnosed obstructive airway disease with sleep symptoms. Amongst 2093 adults included in the study, 48.3% were female and the median age was 63 years (interquartile range 53-72). Two-hundred and five (9.79%) subjects met spirometry criteria for undiagnosed chronic obstructive pulmonary disease, and 191 (9.13%) for undiagnosed asthma. There were no significant associations between spirometry measures and sleep symptoms (p > 0.5), controlling for age, sex, body mass index, smoking and comorbidities. Those with undiagnosed asthma were more likely to report insomnia "at least sometimes" versus "never" (odds ratio 2.58, 95% confidence interval: 1.27-6.19, p = 0.02). Respiratory symptoms were associated with sleep symptoms, with significant (p < 0.05) increases in St George's Respiratory Questionnaire and Chronic Obstructive Pulmonary Disease Assessment Test scores in those reporting most sleep symptoms. Overall, we found an association between undiagnosed asthma and insomnia, and between respiratory and sleep disorder symptoms., (© 2024 The Author(s). Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Background: We investigated dyspnea; its associated risk factors; and its impact on health care utilization, quality of life, and work productivity in adults with undiagnosed respiratory symptoms., Research Question: What is the impact of dyspnea in adults with undiagnosed respiratory symptoms?, Study Design and Methods: This population-based study included 2,857 adults who were experiencing respiratory symptoms. These individuals had not been previously diagnosed with any lung conditions and were recruited from 17 Canadian centers using random digit dialing. Each participant underwent spirometry testing both before and after using a bronchodilator to determine if they met the diagnostic criteria for COPD, asthma, or preserved ratio impaired spirometry (PRISm), or if their spirometry results were normal. An age-matched control group (n = 231) was similarly recruited using random digit dialing. A dyspnea impact assessment score from 0 to 100 was produced using questions from the COPD Assessment Test and St. George's Respiratory questionnaire., Results: Individuals with PRISm (n = 172) reported more impactful dyspnea (mean score, 63.0; 95% CI, 59.5-66.4) than those with undiagnosed asthma (n = 265; mean score, 56.6; 95% CI, 53.9-59.3) or undiagnosed COPD (n = 330; mean score, 57.5; 95% CI, 55.1-59.9). All groups reported significantly more impactful dyspnea than the control group (mean score, 13.8; 95% CI, 11.8-15.7). Patient-specific risk factors including age, sex, BMI, smoking, and comorbidities explained 20.6% of the variation in dyspnea. An additional 12.4% of the variation was explained by disease classification and another 1.7% by the severity of lung function impairment assessed with spirometry. After adjusting for age, sex, and BMI, greater dyspnea impact was associated with increased health care utilization, lower quality of life, and reduced work productivity., Interpretation: Our findings showed that in community-based adults with undiagnosed respiratory symptoms, those identified with PRISm experienced the greatest impact of dyspnea. Dyspnea imposes burdens on the health care system and is associated with impaired quality of life and work productivity., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Many persons with chronic obstructive pulmonary disease (COPD) or asthma have not received a diagnosis, so their respiratory symptoms remain largely untreated., Methods: We used a case-finding method to identify adults in the community with respiratory symptoms without diagnosed lung disease. Participants who were found to have undiagnosed COPD or asthma on spirometry were enrolled in a multicenter, randomized, controlled trial to determine whether early diagnosis and treatment reduces health care utilization for respiratory illness and improves health outcomes. Participants were assigned to receive the intervention (evaluation by a pulmonologist and an asthma-COPD educator who were instructed to initiate guideline-based care) or usual care by their primary care practitioner. The primary outcome was the annualized rate of participant-initiated health care utilization for respiratory illness. Secondary outcomes included changes from baseline to 1 year in disease-specific quality of life, as assessed with the St. George Respiratory Questionnaire (SGRQ; scores range from 0 to 100, with lower scores indicating better health status); symptom burden, as assessed with the COPD Assessment Test (CAT; scores range from 0 to 40, with lower scores indicating better health status); and forced expiratory volume in 1 second (FEV 1 )., Results: Of 38,353 persons interviewed, 595 were found to have undiagnosed COPD or asthma and 508 underwent randomization: 253 were assigned to the intervention group and 255 to the usual-care group. The annualized rate of a primary-outcome event was lower in the intervention group than in the usual-care group (0.53 vs. 1.12 events per person-year; incidence rate ratio, 0.48; 95% confidence interval [CI], 0.36 to 0.63; P<0.001). At 12 months, the SGRQ score was lower than the baseline score by 10.2 points in the intervention group and by 6.8 points in the usual-care group (difference, -3.5 points; 95% CI, -6.0 to -0.9), and the CAT score was lower than the baseline score by 3.8 points and 2.6 points, respectively (difference, -1.3 points; 95% CI, -2.4 to -0.1). The FEV 1 increased by 119 ml in the intervention group and by 22 ml in the usual-care group (difference, 94 ml; 95% CI, 50 to 138). The incidence of adverse events was similar in the trial groups., Conclusions: In this trial in which a strategy was used to identify adults in the community with undiagnosed asthma or COPD, those who received pulmonologist-directed treatment had less subsequent health care utilization for respiratory illness than those who received usual care. (Funded by Canadian Institutes of Health Research; UCAP ClinicalTrials.gov number, NCT03148210.)., (Copyright © 2024 Massachusetts Medical Society.)

Rationale: A significant proportion of individuals with chronic obstructive pulmonary disease (COPD) and asthma remain undiagnosed. Objectives: The objective of this study was to evaluate symptoms, quality of life, healthcare use, and work productivity in subjects with undiagnosed COPD or asthma compared with those previously diagnosed, as well as healthy control subjects. Methods: This multicenter population-based case-finding study randomly recruited adults with respiratory symptoms who had no previous history of diagnosed lung disease from 17 Canadian centers using random digit dialing. Participants who exceeded symptom thresholds on the Asthma Screening Questionnaire or the COPD Diagnostic Questionnaire underwent pre- and post-bronchodilator spirometry to determine if they met diagnostic criteria for COPD or asthma. Two control groups, a healthy group without respiratory symptoms and a symptomatic group with previously diagnosed COPD or asthma, were similarly recruited. Measurements and Main Results: A total of 26,905 symptomatic individuals were interviewed, and 4,272 subjects were eligible. Of these, 2,857 completed pre- and post-bronchodilator spirometry, and 595 (21%) met diagnostic criteria for COPD or asthma. Individuals with undiagnosed COPD or asthma reported greater impact of symptoms on health status and daily activities, worse disease-specific and general quality of life, greater healthcare use, and poorer work productivity than healthy control subjects. Individuals with undiagnosed asthma had symptoms, quality of life, and healthcare use burden similar to those of individuals with previously diagnosed asthma, whereas subjects with undiagnosed COPD were less disabled than those with previously diagnosed COPD. Conclusions: Undiagnosed COPD or asthma imposes important, unmeasured burdens on the healthcare system and is associated with poor health status and negative effects on work productivity.

Background: Some patients with asthma demonstrate normal spirometry and remain undiagnosed without further testing., Objective: To determine clinical predictors of asthma in symptomatic adults with normal spirometry, and to generate a tool to help clinicians decide who should undergo bronchial challenge testing (BCT)., Methods: Using random-digit dialling and population-based case-finding, we recruited adults from the community with respiratory symptoms and no previous history of diagnosed lung disease. Participants with normal pre- and post-bronchodilator spirometry subsequently underwent BCT. Asthma was diagnosed in those with symptoms and a methacholine provocative concentration (PC 20 ) of < 8 mg/ml. Sputum and blood eosinophils, and exhaled nitric oxide were measured. Univariate analyses identified potentially predictive variables, which were then used to construct a multivariable logistic regression model to predict asthma. Model sensitivity, specificity, and area under the receiver operating curve (AUC) were calculated., Results: Of 132 symptomatic individuals with normal spirometry, 34 (26%) had asthma. Of those ultimately diagnosed with asthma, 33 (97%) answered 'yes' to a question asking whether they experienced cough, chest tightness or wheezing provoked by exercise or cold air. Other univariate predictors of asthma included female sex, pre-bronchodilator FEV1 percentage predicted, and percent positive change in FEV1 post bronchodilator. A multivariable model containing these predictive variables yielded an AUC of 0.82 (95% CI: 0.72-0.91), a sensitivity of 82%, and a specificity of 66%. The model was used to construct a nomogram to advise clinicians which patients should be prioritized for BCT., Conclusions: Four readily available patient characteristics demonstrated a high sensitivity and AUC for predicting undiagnosed asthma in symptomatic adults with normal pre- and post-bronchodilator spirometry. These characteristics can potentially help clinicians to decide which individuals with normal spirometry should be investigated with bronchial challenge testing. However, further prospective validation of our decision tool is required., (© 2023. The Author(s).)

Background: Subjects without a previous history of asthma, presenting with unexplained respiratory symptoms and normal spirometry, may exhibit airway hyperresponsiveness (AHR) in association with underlying eosinophilic (type 2 (T2)) inflammation, consistent with undiagnosed asthma. However, the prevalence of undiagnosed asthma in these subjects is unknown., Methods: In this observational study, inhaled corticosteroid-naïve adults without previously diagnosed lung disease reporting current respiratory symptoms and showing normal pre- and post-bronchodilator spirometry underwent fractional exhaled nitric oxide ( F ENO ) measurement, methacholine challenge testing and induced sputum analysis. AHR was defined as a provocative concentration of methacholine causing a 20% fall in forced expiratory volume in 1 s (PC 20 ) <16 mg·mL -1 and T2 inflammation was defined as sputum eosinophils >2% and/or F ENO >25 ppb., Results: Out of 132 subjects (mean±sd age 57.6±14.2 years, 52% female), 47 (36% (95% CI 28-44%)) showed AHR: 20/132 (15% (95% CI 9-21%)) with PC 20 <4 mg·mL -1 and 27/132 (21% (95% CI 14-28%)) with PC 20 4-15.9 mg·mL -1 . Of 130 participants for whom sputum eosinophils, F ENO or both results were obtained, 45 (35% (95% CI 27-43%)) had T2 inflammation. 14 participants (11% (95% CI 6-16%)) had sputum eosinophils >2% and PC 20 ≥16 mg·mL -1 , suggesting eosinophilic bronchitis. The prevalence of T2 inflammation was significantly higher in subjects with PC 20 <4 mg·mL -1 (12/20 (60%)) than in those with PC 20 4-15.9 mg·mL -1 (8/27 (30%)) or ≥16 mg·mL -1 (25/85 (29%)) (p=0.01)., Conclusions: Asthma, underlying T2 airway inflammation and eosinophilic bronchitis may remain undiagnosed in a high proportion of symptomatic subjects in the community who have normal pre- and post-bronchodilator spirometry., Competing Interests: Conflict of interest: L-P. Boulet reports grants from Amgen, AstraZeneca, GlaxoSmithKline, Merck, Novartis and Sanofi Regeneron for participation in multicentre studies and research projects proposed by the investigator; royalties from UptoDate and Taylor & Francis; lecture fees from AstraZeneca, Covis, GlaxoSmithKline, Novartis, Merck and Sanofi; is chair of the Global Initiative for Asthma (GINA) board of directors, president of the Global Asthma Organisation (Interasma), holder of the Laval University Chair on Knowledge Transfer, Prevention and Education in Respiratory and Cardiovascular Health, and member of the Canadian Thoracic Society Respiratory Guidelines Committee. M-È. Boulay has nothing to disclose. A. Côté reports research grants from GlaxoSmithKline; speaker fees from AstraZeneca, GlaxoSmithKline, Valeo and Sanofi; participation in advisory boards for GlaxoSmithKline, AstraZeneca, Sanofi and Valeo. J.M. FitzGerald has attended advisory boards for GlaxoSmithKline, AstraZeneca, Novartis, Sanofi Regeneron and Theravance; received speaker fees/honoraria from AstraZeneca, GlaxoSmithKline, Sanofi Regeneron and Teva; received research funding from the NIH, Canadian Institute for Health Research, AllerGen National Centre for Excellence, GlaxoSmithKline, AstraZeneca, Sanofi Regeneron, Teva and Novartis, all paid directly to his institution; and was a member of the steering committee for the International Severe Asthma Registry, Principal Investigator for the Canadian Severe Asthma Registry, and member of the GINA Science and Executive Committees. C. Bergeron reports consulting fees from Sanofi, AstraZeneca and Takeda; payments for presentations from Grifols, AstraZeneca, Sanofi and Valeo. C. Lemière reports royalties from UptoDate; consulting fees from GlaxoSmithKline, AstraZeneca and Sanofi; payments for presentations from GlaxoSmithKline, AstraZeneca and Sanofi. M.D. Lougheed reports grants from the Manitoba Workers Compensation Board, Ontario Lung Association, Ontario Thoracic Society, Government of Ontario's Innovation Fund, Queen's University, AstraZeneca and GlaxoSmithKline; payments for co-development and co-presentation of a severe asthma preparation course from the Canadian Thoracic Society and for co-development of an accredited CME module on severe asthma from MDBriefcase; participation on advisory board for AstraZeneca; membership on the Canadian Thoracic Society Asthma Clinical Assembly and Canadian Thoracic Society Asthma Clinical Assembly Steering Committee, Health Quality Ontario's Asthma in Adults and Asthma in Children Quality Standard Advisory Committee; is past chair of the Canadian Thoracic Society Asthma Clinical Assembly, is a Canadian Thoracic Society representative on the Lung Association's board of directors and a Canadian Thoracic Society representative to the European Respiratory Society. K.L. Vandemheen has nothing to declare. S.D. Aaron reports payments for lectures from AstraZeneca, GlaxoSmithKline and Sanofi; participation on advisory boards for AstraZeneca, GlaxoSmithKline, Sanofi and Covis., (Copyright ©The authors 2023. For reproduction rights and permissions contact permissions@ersnet.org.)

Background: It remains unclear why some symptomatic individuals with asthma or COPD remain undiagnosed. Here, we compare patient and physician characteristics between symptomatic individuals with obstructive lung disease (OLD) who are undiagnosed and individuals with physician-diagnosed OLD., Methods: Using random-digit dialling and population-based case finding, we recruited 451 participants with symptomatic undiagnosed OLD and 205 symptomatic control participants with physician-diagnosed OLD. Data on symptoms, quality of life and healthcare utilisation were analysed. We surveyed family physicians of participants in both groups to elucidate differences in physician practices that could contribute to undiagnosed OLD., Results: Participants with undiagnosed OLD had lower mean pre-bronchodilator forced expiratory volume in 1 s percentage predicted compared with those who were diagnosed (75.2% versus 80.8%; OR 0.975, 95% CI 0.963-0.987). They reported greater psychosocial impacts due to symptoms and worse energy and fatigue than those with diagnosed OLD. Undiagnosed OLD was more common in participants whose family physicians were practising for >15 years and in those whose physicians reported that they were likely to prescribe respiratory medications without doing spirometry. Undiagnosed OLD was more common among participants who had never undergone spirometry (OR 10.83, 95% CI 6.18-18.98) or who were never referred to a specialist (OR 5.92, 95% CI 3.58-9.77). Undiagnosed OLD was less common among participants who had required emergency department care (OR 0.44, 95% CI 0.20-0.97)., Conclusions: Individuals with symptomatic undiagnosed OLD have worse pre-bronchodilator lung function and present with greater psychosocial impacts on quality of life compared with their diagnosed counterparts. They were less likely to have received appropriate investigations and specialist referral for their respiratory symptoms., Competing Interests: Conflict of interest: M. Cherian reports no conflict of interest. K.M.A. Magner reports no conflict of interest. G.A. Whitmore reports no conflict of interest. K.L. Vandemheen reports no conflict of interest. C. Bergeron reports grants, contracts or honoraria from Novartis, Biohaven, AstraZeneca, Sanofi, Valeo and Grifols; and advisory board participation Sanofi, AstraZeneca, GlaxoSmithKline, Takeda and Valeo. L-P. Boulet reports grants, contracts, consulting fees or honoraria from Amgen, AstraZeneca, GlaxoSmithKline, Merck, Sanofi-Regeneron, Covis and Novartis; royalties or licences from UptoDate and Taylor & Francis; leadership roles with the Global Initiative for Asthma (GINA), Global Asthma Association (INTERASMA) and Canadian Thoracic Society; and holds the Laval University Chair on Knowledge Transfer, Prevention and Education in Respiratory and Cardiovascular Health. A. Cote reports grants, contracts, consulting fees or honoraria from GlaxoSmithKline, AstraZeneca, Valeo, Sanofi-Regeneron and Covis; and advisory board participation with AstraZeneca, Sanofi and Valeo. S.K. Field reports grants, contracts, consulting fees or honoraria from Bayer, Insmed, Merck, Valeo and GlaxoSmithKline. E. Penz reports grants, contracts, consulting fees or honoraria from the Saskatchewan Health Research Foundation, CIHR, Respiratory Research Centre, SCPOR, AstraZeneca, Saskatchewan Cancer Agency, GlaxoSmithKline, Sanofi, Genzyme, ICBEM and Boehringer Ingelheim; and leadership roles with the Canadian Thoracic Society COPD Assembly, CIHR Institute Advisory Board and Youth4Change. R.A. McIvor reports no conflict of interest. C. Lemière repots grants, contracts, consulting fees or honoraria from GlaxoSmithKline, AstraZeneca, Sanofi and Novartis; and royalties or licences from UptoDate. S. Gupta reports no conflict of interest. I. Mayers reports no conflict of interest. M. Bhutani reports grants, contracts, consulting fees, support for travel or honoraria from the CIHR, AstraZeneca, GlaxoSmithKline, Novartis, Grifols, Sanofi, Covis, Valeo, Lung Association of Saskatchewan, Canadian Thoracic Society and Lung Association of Alberta and Northwest Territories; and leadership roles with the Canadian Thoracic Society and Alberta Health Services. P. Hernandez reports grants, contracts, support for travel or honoraria from the CIHR, Cyclomedia, Boehringer Ingelheim, Vertex, Grifols, AstraZeneca, Boehringer Ingelheim, Janssen and Canadian Thoracic Society; advisory board participation with Acceleron, AstraZeneca, Boehringer Ingelheim, Covis, GlaxoSmithKline, Grifols, Janssen, Novartis, Sanofi, Takeda and Valeo; and leadership roles with the Canadian Thoracic Society. M.D. Lougheed reports grants, contracts or honoraria from the CIHR, AstraZeneca, GlaxoSmithKline, Canadian Thoracic Society and MDBriefcase; advisory board participation with AstraZeneca; leadership roles with the Canadian Thoracic Society, Health Quality Ontario and the Lung Association. C.J. Licskai reports no conflict of interest. T. Azher reports no conflict of interest. M. Ainslie reports no conflict of interest. N. Ezer reports grants, contracts or honoraria from the CIHR, Rossy Cancer Network, Covis Pharma, GlaxoSmithKline, AstraZeneca, Fédération des Omnipracticiens du Québec and Médecin du Québec Magazine; advisory board participation with GlaxoSmithKline; leadership role with the Quebec Ministry of Health Lung Cancer Screening Implementation Committee; and receipt of study drug from Covis. S. Mulpuru reports no conflict of interest. S.D. Aaron reports honoraria from AstraZeneca, Sanofi and GlaxoSmithKline; and advisory board participation with AstraZeneca, GlaxoSmithKline and Sanofi., (Copyright ©The authors 2023. For reproduction rights and permissions contact permissions@ersnet.org.)

Background: Many people with asthma and COPD remain undiagnosed. We developed and validated a new case-finding questionnaire to identify symptomatic adults with undiagnosed obstructive lung disease., Methods: Adults in the community with no prior history of physician-diagnosed lung disease who self-reported respiratory symptoms were contacted via random-digit dialling. Pre- and post-bronchodilator spirometry was used to confirm asthma or COPD. Predictive questions were selected using multinomial logistic regression with backward elimination. Questionnaire performance was assessed using sensitivity, predictive values and area under the receiver operating characteristic curve (AUC). The questionnaire was assessed for test-retest reliability, acceptability and readability. External validation was prospectively conducted in an independent sample and predictive performance re-evaluated., Results: A 13-item Undiagnosed COPD and Asthma Population Questionnaire (UCAP-Q) case-finding questionnaire to predict undiagnosed asthma or COPD was developed. The most appropriate risk cut-off was determined to be 6% for either disease. Applied to the derivation sample (n=1615), the questionnaire yielded a sensitivity of 92% for asthma and 97% for COPD; specificity of 17%; and an AUC of 0.69 (95% CI 0.64-0.74) for asthma and 0.82 (95% CI 0.78-0.86) for COPD. Prospective validation using an independent sample (n=471) showed sensitivities of 93% and 92% for asthma and COPD, respectively; specificity of 19%; with AUCs of 0.70 (95% CI 0.62-0.79) for asthma and 0.81 (95% CI 0.74-0.87) for COPD. AUCs for UCAP-Q were higher compared to AUCs for currently recommended case-finding questionnaires for asthma or COPD., Conclusions: The UCAP-Q demonstrated high sensitivities and AUCs for identifying undiagnosed asthma or COPD. A web-based calculator allows for easy calculation of risk probabilities for each disease., Competing Interests: Conflict of interest: C. Huynh reports no conflicts of interest. G.A. Whitmore reports no conflicts of interest. K.L. Vandemheen reports no conflicts of interest. J.M. FitzGerald reports no conflicts of interest. C. Bergeron reports no conflicts of interest. L-P. Boulet reports receiving grants, consulting fees or honoraria from Amgen, AstraZeneca, GlaxoSmithKline, Merck, Novartis and Sanofi-Regeneron. A. Cote reports receiving honoraria from GlaxoSmithKline, AstraZeneca, Sanofi and Covis. S.K. Field reports receiving consulting fees or honoraria from Merck, GlaxoSmithKline, Novartis and Boehringer Ingelheim. E. Penz reports receiving honoraria from AstraZeneca, GlaxoSmithKline, Novartis, ICEBM and Boehringer Ingelheim. R.A. McIvor reports no conflicts of interest. C. Lemière reports receiving consulting fees or honoraria from Sanofi, TEVA, GlaxoSmithKline and AstraZeneca. S. Gupta reports no conflicts of interest. I. Mayers reports no conflicts of interest. M. Bhutani reports payments or honoraria from AZ, GSK, Novartis, Grifols, Sanofi, Covis and Valeo. P. Hernandez reports payments or honoraria from AZ, GSK, Novartis and Valeo. M.D. Lougheed reports receiving grants from AZ and GSK. C.J. Licskai reports receiving honoraria from AstraZeneca, GlaxoSmithKline, Novartis and Boehringer Ingelheim. T. Azher reports no conflicts of interest. M. Ainslee reports receiving honoraria from Boehringer Ingelheim. I. Fraser reports no conflicts of interest. M. Mahdavian reports no conflicts of interest. G.G. Alvarez reports no conflicts of interest. T. Kendzerska reports speaker honoraria from AstraZeneca. S.D. Aaron reports sitting on advisory boards and honoraria payments from GlaxoSmithKline, Sanofi and AstraZeneca., (Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.)

Background: The actual burden of COPD and asthma may be much higher than appreciated, since a large proportion of individuals are not diagnosed. Our study objective was to compare health care utilization, burden of symptoms and quality of life in subjects with self-reported respiratory symptoms who were subsequently found to have undiagnosed airflow obstruction compared to those having no airflow obstruction., Methods: This cross-sectional case-finding study used data from the Undiagnosed COPD and Asthma Population (UCAP) study. Adult subjects with respiratory symptoms who had no history of diagnosed lung disease were recruited in a two-step case-finding process using random digit-dialling of land lines and cell phones located within a 90-min radius of 16 Canadian study sites. Participants were assessed for COPD, asthma or no airflow obstruction using pre- and post-bronchodilator spirometry based on American Thoracic Society diagnostic criteria., Results: 1660 participants were recruited, of these 1615 had adequate spirometry and 331 (20.5%) subjects met spirometry criteria for undiagnosed asthma or COPD. Subjects with undiagnosed asthma or COPD had increased respiratory symptoms as assessed by the COPD Assessment Test (CAT), and higher St. George's Respiratory Questionnaire (SGRQ) scores indicating worse health-related quality of life, compared to subjects with no airflow obstruction. No between-group differences were found in health care utilization or work or school absenteeism., Conclusion: Undiagnosed asthma and COPD are common in Canadian adults experiencing breathing problems and are associated with a greater burden of symptoms and poorer health-related quality of life. These results suggest that patients may benefit from early identification and treatment of undiagnosed asthma and COPD., Competing Interests: Declaration of competing interest All authors in this paper declare that they have no conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: In patients with a history suggestive of asthma, diagnosis is usually confirmed by spirometry with bronchodilator response (BDR) or confirmatory methacholine challenge testing (MCT)., Research Question: We examined the proportion of participants with negative BDR testing who had a positive MCT (and its predictors) result and characteristics of MCT, including effects of controller medication tapering and temporal variability (and predictors of MCT result change), and concordance between MCT and pulmonologist asthma diagnosis., Study Design and Methods: Adults with self-reported physician-diagnosed asthma were recruited by random-digit dialing across Canada. Subjects performed spirometry with BDR testing and returned for MCT if testing was nondiagnostic for asthma. Subjects on controllers underwent medication tapering with serial MCTs over 3 to 6 weeks. Subjects with a negative MCT (the provocative concentration of methacholine that results in a 20% drop in FEV 1 [PC 20 ] > 8 mg/mL) off medications were examined by a pulmonologist and had serial MCTs after 6 and 12 months., Results: Of 500 subjects (50.5 ± 16.6 years old, 68.0% female) with a negative BDR test for asthma, 215 (43.0%) had a positive MCT. Subjects with prebronchodilator airflow limitation were more likely to have a positive MCT (OR, 1.90; 95% CI, 1.17-3.04). MCT converted from negative to positive, with medication tapering in 18 of 94 (19.1%) participants, and spontaneously over time in 25 of 165 (15.2%) participants. Of 231 subjects with negative MCT, 28 (12.1%) subsequently received an asthma diagnosis from a pulmonologist., Interpretation: In subjects with a self-reported physician diagnosis of asthma, absence of bronchodilator reversibility had a negative predictive value of only 57% to exclude asthma. A finding of spirometric airflow limitation significantly increased chances of asthma. MCT results varied with medication taper and over time, and pulmonologists were sometimes prepared to give a clinical diagnosis of asthma despite negative MCT. Correspondingly, in patients for whom a high clinical suspicion of asthma exists, repeat testing appears to be warranted., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: ∼5-10% of adults may have undiagnosed airflow obstruction. The objective of this study was to develop a population-based case-finding strategy to assess the prevalence of undiagnosed airflow obstruction (asthma or COPD) amongst adults with respiratory symptoms in Canada., Methods: Adults without a previous history of asthma, COPD or lung disease were recruited using random digit-dialling and asked if they had symptoms of dyspnoea, cough, sputum or wheeze within the past 6 months. Those who answered affirmatively completed the Asthma Screening Questionnaire (ASQ), COPD-Diagnostic Questionnaire (COPD-DQ) and COPD Assessment Test (CAT). Those with an ASQ score of ≥6 or a COPD-DQ score of ≥20 underwent pre- and post-bronchodilator spirometry to diagnose asthma or COPD., Results: 12 117 individuals were contacted at home and assessed for study eligibility. Of the 1260 eligible individuals, 910 (72%) enrolled and underwent spirometry. Ultimately, 184 subjects (20% of those enrolled) had obstructive lung disease (73 asthma and 111 COPD). Individuals found to have undiagnosed asthma or COPD had more severe respiratory symptoms and impaired quality of life compared with those without airflow obstruction. The ASQ, COPD-DQ, and CAT had ROC areas for predicting undiagnosed asthma or COPD of 0.49, 0.64 and 0.56, respectively. Four descriptive variables (age, BMI, sex and pack-years smoked) produced better receiver operating characteristic (ROC) values than the questionnaires (ROC area=0.68)., Conclusion: 20% of randomly selected individuals who report respiratory symptoms in Canada have undiagnosed airflow obstruction due to asthma or COPD. Questionnaires could exclude subjects at low risk but lack the ability to accurately find subjects with undiagnosed disease., Competing Interests: Conflict of interest: M. Preteroti has nothing to disclose. Conflict of interest: G.A. Whitmore has nothing to disclose. Conflict of interest: K.L. Vandemheen has nothing to disclose. Conflict of interest: J.M. FitzGerald has nothing to disclose. Conflict of interest: C. Lemiere reports grants and personal fees for advisory board work, consultancy and lectures from AstraZeneca, grants and personal fees for advisory board work and lectures from TEVA Innovation, personal fees for advisory board work and consultancy from GlaxoSmithKline, personal fees for advisory board work from Sanofi, outside the submitted work. Conflict of interest: L-P. Boulet reports research grants for participation in multicentre studies from AstraZeneca, Boston Scientific, GlaxoSmithKline, Hoffman La Roche, Novartis, Ono Pharma, Sanofi and Takeda, support for research projects introduced by the investigator from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Merck and Takeda, fees for consulting and advisory boards from AstraZeneca, Novartis and Methapharm, nonprofit grants for production of educational materials from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Merck and Novartis, conference fees from AstraZeneca, GlaxoSmithKline, Merck and Novartis, support for participation in conferences and meetings from Novartis and Takeda. Conflict of interest: E. Penz reports CIHR funding of UCAP study, during the conduct of the study; grants, personal fees for advisory board work, consultancy and lectures, and non-financial (travel) support from AstraZeneca, personal fees for advisory board work and non-financial (travel) support from GlaxoSmithKline and Boehringer Ingelheim, outside the submitted work. Conflict of interest: S.K. Field reports grants from GSK, InsMed, Novartis and Boehringer Ingelheim, outside the submitted work. Conflict of interest: S. Gupta has nothing to disclose. Conflict of interest: R.A. McIvor has nothing to disclose. Conflict of interest: I. Mayers has nothing to disclose. Conflict of interest: P. Hernandez reports grants from CIHR, during the conduct of the study; personal fees for consultancy from Actelion, GlaxoSmithKline, Novartis, Sanofi and Teva, personal fees for consultancy and educational activities from AstraZeneca, grants and personal fees for consultancy and educational activities from Boehringer Ingelheim, grants from Cyclomedica, Grifols and Prometic, outside the submitted work. Conflict of interest: D. Lougheed reports grants from AstraZeneca, GlaxoSmithKline, Hoffman LaRoche Ltd, Novartis, Government of Ontario's Innovation Fund, Allergen NCE, Janssen, Canadian Institutes of Health Research, Manitoba Workers Compensation Board and Ontario Lung Association/Canada Health Infoway, grants and honoraria for educational activities from Ontario Lung Association, honoraria for educational activities from Canadian Thoracic Society, honoraria for advisory board work from AstraZeneca PRECISION Program, outside the submitted work; and is the nominated Canadian Thoracic Society representative on the Canadian Lung Association's Board of Directors. Conflict of interest: M. Ainslie has nothing to disclose. Conflict of interest: C. Licskai reports grants and personal fees from AstraZeneca, Boehringer Ingelheim, Novartis and Pfizer, personal fees from GSK, outside the submitted work. Conflict of interest: T. Azher has nothing to disclose. Conflict of interest: I. Fraser has nothing to disclose. Conflict of interest: M. Madavian reports personal fees for lectures from AstraZeneca, personal fees for lectures and non-financial (drug sample) support from Novartis and Boehringer Ingelheim, non-financial (drug sample) support from GSK, outside the submitted work. Conflict of interest: S.D. Aaron has nothing to disclose., (Copyright ©ERS 2020.)

Rationale: Patients with uncontrolled, persistent asthma can show substantial health improvements when administered placebo. Objectives: We analyzed five randomized, placebo-controlled clinical trials that assessed subjects with uncontrolled, persistent asthma to determine the magnitudes of placebo effects across different clinical outcomes. Methods: Placebo effects for objective asthma-related outcomes, healthcare utilization outcomes, and patient-reported outcomes were estimated, with adjustments for regression to the mean. Results: Statistically significant improvements in all clinical outcomes were seen in patients randomized to placebo across all trials. Placebo effects were largest for healthcare utilization outcomes, including exacerbations (median reduction, 0.44 events/yr; 31% risk reduction; range, 19-56%), emergency department visits (median reduction, 0.19 events/yr; 50% risk reduction; range, 36-82%), and hospitalizations for asthma (median reduction, 0.26 events/yr; 66% risk reduction; range, 61-74%). Patient-reported outcomes exhibited intermediate placebo effects. Median improvements in the Asthma Control Questionnaire and St. George's Respiratory Questionnaire scores in placebo-treated patients were 0.53 units (25% improvement; range, 18-30%) and 8.3 units (19.5% improvement; range 19-20%), respectively. Forced expiratory volume in 1 second exhibited the smallest relative placebo effects (median increase, 77 ml; 4.2% improvement; range, 3.4-4.9%). Subgroup analyses did not reveal patient subgroups that were more susceptible to placebo effects. Pre- and postrandomization counts for asthma exacerbations showed patterns consistent with the expected negative binomial distribution except for significant departures in prerandomization exacerbations for two trials. Conclusions: Patients with uncontrolled asthma derived consistent benefit from randomization to placebo. Observed placebo effects may represent beneficial effects of both sham therapy and a structured asthma regimen dictated by the study protocol. In the case of healthcare utilization outcomes, recall errors in self-reported healthcare events may have introduced biases that inflated placebo effect estimates.

Rationale: The reliability of using between-visit variation in forced expiratory volume in 1 second (FEV 1 ) to diagnose asthma is understudied, and hence uncertain., Objective: To determine whether FEV 1 variability measured over recurrent visits is significantly associated with a diagnosis of current asthma., Methods: Randomly selected adults (N = 964) with a history of physician-diagnosed asthma were studied from 2005 to 2007 and from 2012 to 2016. A diagnosis of current asthma was confirmed in those participants who exhibited bronchial hyperresponsiveness to methacholine and/or acute worsening of asthma symptoms while being weaned off asthma medications. Regression analyses and receiver operating curves were used to evaluate the ability of between-visit FEV 1 variability to diagnose asthma., Results: A current diagnosis of asthma was confirmed in 584 of 964 participants (60%). Between-visit absolute variability in FEV 1 was significantly greater in those in whom current asthma was confirmed, compared with those in whom current asthma was ruled out (7.3% vs. 4.8%; mean difference between the two groups, 2.5%; 95% confidence interval, 1.7-3.3%). However, a 12% and 200-ml between-visit variation in FEV 1 , which is the diagnostic threshold recommended by Global Initiative for Asthma, exhibited a sensitivity of only 0.17 and a specificity of 0.94 for confirming current asthma. A between-visit absolute variability in FEV 1  ≥ 12% and 200 ml increased the pretest probability of asthma from 60% to a posttest probability of 81%., Conclusions: A 12% and 200-ml between-visit variation in FEV 1 , if present, has reasonably good specificity for diagnosing asthma, but has poor sensitivity compared with bronchial challenge testing. Between-visit variability in FEV 1 is a relatively unhelpful test to establish a diagnosis of asthma.

Importance: Although asthma is a chronic disease, the expected rate of spontaneous remissions of adult asthma and the stability of diagnosis are unknown., Objective: To determine whether a diagnosis of current asthma could be ruled out and asthma medications safely stopped in randomly selected adults with physician-diagnosed asthma., Design, Setting, and Participants: A prospective, multicenter cohort study was conducted in 10 Canadian cities from January 2012 to February 2016. Random digit dialing was used to recruit adult participants who reported a history of physician-diagnosed asthma established within the past 5 years. Participants using long-term oral steroids and participants unable to be tested using spirometry were excluded. Information from the diagnosing physician was obtained to determine how the diagnosis of asthma was originally made in the community. Of 1026 potential participants who fulfilled eligibility criteria during telephone screening, 701 (68.3%) agreed to enter into the study. All participants were assessed with home peak flow and symptom monitoring, spirometry, and serial bronchial challenge tests, and those participants using daily asthma medications had their medications gradually tapered off over 4 study visits. Participants in whom a diagnosis of current asthma was ultimately ruled out were followed up clinically with repeated bronchial challenge tests over 1 year., Exposure: Physician-diagnosed asthma established within the past 5 years., Main Outcomes and Measures: The primary outcome was the proportion of participants in whom a diagnosis of current asthma was ruled out, defined as participants who exhibited no evidence of acute worsening of asthma symptoms, reversible airflow obstruction, or bronchial hyperresponsiveness after having all asthma medications tapered off and after a study pulmonologist established an alternative diagnosis. Secondary outcomes included the proportion with asthma ruled out after 12 months and the proportion who underwent an appropriate initial diagnostic workup for asthma in the community., Results: Of 701 participants (mean [SD] age, 51 [16] years; 467 women [67%]), 613 completed the study and could be conclusively evaluated for a diagnosis of current asthma. Current asthma was ruled out in 203 of 613 study participants (33.1%; 95% CI, 29.4%-36.8%). Twelve participants (2.0%) were found to have serious cardiorespiratory conditions that had been previously misdiagnosed as asthma in the community. After an additional 12 months of follow-up, 181 participants (29.5%; 95% CI, 25.9%-33.1%) continued to exhibit no clinical or laboratory evidence of asthma. Participants in whom current asthma was ruled out, compared with those in whom it was confirmed, were less likely to have undergone testing for airflow limitation in the community at the time of initial diagnosis (43.8% vs 55.6%, respectively; absolute difference, 11.8%; 95% CI, 2.1%-21.5%)., Conclusions and Relevance: Among adults with physician-diagnosed asthma, a current diagnosis of asthma could not be established in 33.1% who were not using daily asthma medications or had medications weaned. In patients such as these, reassessing the asthma diagnosis may be warranted.

Background: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) result in considerable morbidity and mortality. However, there are no objective biomarkers to diagnose AECOPD., Methods: We used multiple reaction monitoring mass spectrometry to quantify 129 distinct proteins in plasma samples from patients with COPD. This analytical approach was first performed in a biomarker cohort of patients hospitalized with AECOPD (Cohort A, n = 72). Proteins differentially expressed between AECOPD and convalescent states were chosen using a false discovery rate <0.01 and fold change >1.2. Protein selection and classifier building were performed using an elastic net logistic regression model. The performance of the biomarker panel was then tested in two independent AECOPD cohorts (Cohort B, n = 37, and Cohort C, n = 109) using leave-pair-out cross-validation methods., Results: Five proteins were identified distinguishing AECOPD and convalescent states in Cohort A. Biomarker scores derived from this model were significantly higher during AECOPD than in the convalescent state in the discovery cohort (p<0.001). The receiver operating characteristic cross-validation area under the curve (CV-AUC) statistic was 0.73 in Cohort A, while in the replication cohorts the CV-AUC was 0.77 for Cohort B and 0.79 for Cohort C., Conclusions: A panel of five biomarkers shows promise in distinguishing AECOPD from convalescence and may provide the basis for a clinical blood test to diagnose AECOPD. Further validation in larger cohorts is necessary for future clinical translation.

Background: Airway proliferation of Pseudomonas aeruginosa bacteria is thought to trigger CF exacerbations and may be affected by the presence of viral infections., Methods: A 2-year prospective study was conducted on 35 adults with CF. P. aeruginosa sputum density was analyzed during stable, exacerbation and post exacerbation assessments. Upon exacerbation, samples were sent for PCR detection of respiratory viruses and the sputum density of P. aeruginosa in patients with a viral infection versus those without was compared., Results: Twenty-two patients experienced 30 exacerbations during the study period; 50% were associated with a viral infection. There was no change in sputum density of P. aeruginosa from the stable to exacerbation state when measured by quantitative culture or by PCR. Virus-associated exacerbations did not result in significant increases in P. aeruginosa sputum density compared to non-viral exacerbations., Conclusion: Sputum density of P. aeruginosa was not increased at the time of CF exacerbation and was not influenced by the presence of viral infection., (Copyright © 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Background: The decision to have lung transplantation as treatment for end-stage lung disease from cystic fibrosis (CF) has benefits and serious risks. Although patient decision aids are effective interventions for helping patients reach a quality decision, little is known about implementing them in clinical practice. Our study evaluated a sustainable approach for implementing a patient decision aid for adults with CF considering referral for lung transplantation., Methods: A prospective pragmatic observational study was guided by the Knowledge-to-Action Framework. Healthcare professionals in all 23 Canadian CF clinics were eligible. We surveyed participants regarding perceived barriers and facilitators to patient decision aid use. Interventions tailored to address modifiable identified barriers included training, access to decision aids, and conference calls. The primary outcome was >80% use of the decision aid in year 2., Results: Of 23 adult CF clinics, 18 participated (78.2%) and 13 had healthcare professionals attend training. Baseline barriers were healthcare professionals' inadequate knowledge for supporting patients making decisions (55%), clarifying patients' values for outcomes of options (58%), and helping patients handle conflicting views of others (71%). Other barriers were lack of time (52%) and needing to change how transplantation is discussed (42%). Baseline facilitators were healthcare professionals feeling comfortable discussing bad transplantation outcomes (74%), agreeing the decision aid would be easy to experiment with (71%) and use in the CF clinic (87%), and agreeing that using the decision aid would not require reorganization of the CF clinic (90%). After implementing the decision aid with interventions tailored to the barriers, decision aid use increased from 29% at baseline to 85% during year 1 and 92% in year 2 (p < 0.001). Compared to baseline, more healthcare professionals at the end of the study were confident in supporting decision-making (p = 0.03) but continued to feel inadequate ability with supporting patients to handle conflicting views (p = 0.01)., Conclusion: Most Canadian CF clinics agreed to participate in the study. Interventions were used to target identified modifiable barriers to using the patient decision aid in routine CF clinical practice. CF clinics reported using it with almost all patients in the second year.

Our objective was to describe the natural history of infection with transmissible and unique strains of P. aeruginosa (PA) in adult CF patients and to determine if clearance of PA from sputum was associated with an improvement in clinical status. This was a 3-year prospective cohort study of adult patients with CF. Sputum was collected at baseline and annually. Rate of decline of FEV1, BMI, exacerbation rate, and time to death or transplant were compared between patients who cleared PA versus those in whom PA was persistent. A total of 373 patients were included in the study, 75% were infected with PA at baseline; 24% were infected with transmissible strains and 51% with unique strains. Patients infected with unique strains were more likely to clear PA from their sputum over 3 years compared to those infected with transmissible strains (19% vs 10%, P=0.05). Declines in FEV1 and rates of pulmonary exacerbations, deaths, or lung transplants were not different between patients who cleared PA compared to those who remained persistently infected. No clinical benefit was identified in patients who cleared PA from sputum compared to those who remained persistently infected.

Background: Many patients with cystic fibrosis develop persistent airway infection/colonization with Aspergillus fumigatus, however the impact of A. fumigatus on clinical outcomes remains unclear. The objective of this study was to determine whether treatment directed against Aspergillus fumigatus improves pulmonary function and clinical outcomes in patients with cystic fibrosis (CF)., Methods: We performed a double-blind randomized placebo-controlled pilot clinical trial involving 35 patients with CF whose sputum cultures were chronically positive for A. fumigatus. Participants were centrally randomized to receive either oral itraconazole 5 mg/kg/d (N = 18) or placebo (N = 17) for 24 weeks. The primary outcome was the proportion of patients who experienced a respiratory exacerbation requiring intravenous antibiotics over the 24 week treatment period. Secondary outcomes included changes in FEV(1) and quality of life., Results: Over the 24 week treatment period, 4 of 18 (22%) patients randomized to itraconazole experienced a respiratory exacerbation requiring intravenous antibiotics, compared to 5 of 16 (31%) placebo treated patients, P = 0.70. FEV(1) declined by 4.62% over 24 weeks in the patients randomized to itraconazole, compared to a 0.32% improvement in the placebo group (between group difference = -4.94%, 95% CI: -15.33 to 5.45, P = 0.34). Quality of life did not differ between the 2 treatment groups throughout the study. Therapeutic itraconazole blood levels were not achieved in 43% of patients randomized to itraconazole., Conclusion: We did not identify clinical benefit from itraconazole treatment for CF patients whose sputum was chronically colonized with A. fumigatus. Limitations of this pilot study were its small sample size, and failure to achieve therapeutic levels of itraconazole in many patients., Trial Registration: ClinicalTrials.gov NCT00528190.

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 (FEV(1)); 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.

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.

It was recently shown that 30% of adults with a physician diagnosis of asthma did not have asthma when objectively assessed using a four-step algorithm involving serial spirometry, bronchial challenge testing and subsequent tapering of asthma medications. The objective of the present study was to determine how many steps in the algorithm were required in order to confirm asthma, and whether any patient-related variables were associated with earlier asthma confirmation. A total of 540 subjects with a previous physician diagnosis of asthma were randomly recruited from the community. The number of subjects confirmed with asthma at each study visit was calculated. Regression analysis was used to determine variables associated with earlier asthma confirmation. Of the 499 subjects who completed the diagnostic algorithm, 346 (69%) had asthma confirmed and 150 (30%) had asthma excluded. Of subjects in whom asthma was confirmed, including those using regular asthma controlling medications, >90% were confirmed with only one or two study visits, by either pre- and post-bronchodilator spirometry or a single bronchial challenge test. Only 46 (9%) out of 499 subjects required tapering of asthma medications and repeated bronchial challenge tests for exclusion or confirmation of asthma. Lower forced expiratory volume in 1 s and younger age were associated with earlier asthma confirmation. For the majority with a previous physician diagnosis of asthma, only pre- and post-bronchodilator spirometry and a single methacholine challenge test are required in order to confirm asthma.

Background: We analyzed serial concentrations of multiple inflammatory mediators from serum and induced sputum obtained from patients with stable COPD and controls. The objective was to determine which proteins could be used as reliable biomarkers to assess COPD disease state and severity., Methods: Forty-two subjects; 21 with stable COPD and 21 controls, were studied every 2 weeks over a 6-week period. Serum and induced sputum were obtained at each of 3 visits and concentrations of 19 serum and 22 sputum proteins were serially assessed using multiplex immunoassays. We used linear mixed effects models to test the distribution of proteins for an association with COPD and disease severity. Measures of within- and between-subject coefficients of variation were calculated for each of the proteins to assess reliability of measurement., Results: There was significant variability in concentrations of all inflammatory proteins over time, and variability was greater for sputum proteins (median intra-subject coefficient of variation 0.58) compared to proteins measured in serum (median intra-subject coefficient of variation 0.32, P = 0.03). Of 19 serum proteins and 22 sputum proteins tested, only serum CRP, myeloperoxidase and VEGF and sputum IL-6, IL-8, TIMP-1, and VEGF showed acceptable intra and inter-patient reliability and were significantly associated with COPD, the severity of lung function impairment, and dyspnea., Conclusions: Levels of many serum and sputum biomarkers cannot be reliably ascertained based on single measurements. Multiple measurements over time can give a more reliable and precise estimate of the inflammatory burden in clinically stable COPD patients.

Context: Most adults with cystic fibrosis are eventually required to make a decision about referral for lung transplantation., Objective: To identify the decisional needs of these patients and to develop a decision aid to address these needs., Methods: A comprehensive review of the literature, a review of Canadian transplant statistics from 2002 to 2006, and a self-assessment survey of patients who had already made a decision about referral were performed to identify the decisional needs of patients. A decision aid was then developed and evaluated by an expert panel of health care professionals and patients., Results: Transplant referral patterns vary widely among Canadian cystic fibrosis clinics. Canadian patients with cystic fibrosis who were not residing in transplant centers between 2002 and 2006 were significantly less likely to undergo lung transplants (P < .001). Decisional needs identified by patients included wanting more information on (1) relocation to the transplant center, (2) the benefits and risks of surgery, and (3) how to cope with anxiety and depression when making the decision. In response to these identified needs, a decision aid for lung transplantation was developed. A panel of health care professionals and patients reviewed the decision aid and agreed that the content was appropriate, easy to understand, and unbiased., Conclusion: The decisional needs of patients with cystic fibrosis who are considering lung transplantation are not being addressed in Canadian cystic fibrosis clinics, especially in clinics outside of transplant centers. An evidence-based decision aid could serve as a useful tool to help address these needs.

Background: Bacteria grow as biofilms within CF airways. However, antibiotic susceptibility testing is routinely performed on planktonically-growing bacteria. This study assessed whether CF patients infected with multiresistant organisms had improved clinical outcomes if given antibiotics that inhibited their biofilm-grown bacteria., Methods: 110 patients with pulmonary exacerbations were treated with intravenous antibiotics based on susceptibility testing of planktonically-growing bacteria. A retrospective analysis was done using bacterial isolates grown from their sputum at exacerbation. Each isolate was grown as a biofilm and combination antibiotic susceptibility testing was performed. Clinical outcomes in patients treated with biofilm-susceptible antibiotics were compared to those that were not., Results: 66 of 110 patients (60%) were treated with antibiotic combinations that inhibited all of their planktonically-grown bacterial isolates, however, when the same isolates were grown as biofilms, only 24 patients (22%) had all of their biofilm-grown isolates remaining susceptible to the antibiotics (P=<0.001 ). When patients with at least one biofilm-grown susceptible isolate (n=61) were compared to those with none (n=49), there was a significant decrease in sputum bacterial density (P=0.02) and length of stay (P=0.04) and a non-significant decrease in treatment failure. Survival analyses of time to next exacerbation showed non-significant trends favoring patients treated with biofilm-effective antibiotics., Conclusions: Most patients with CF exacerbations do not receive antibiotics that inhibit all biofilm-grown bacteria from their sputum at exacerbation. Patients treated with biofilm-effective therapy seemed to have improved clinical outcomes.

The aim of the present investigation was to develop a novel approach for rapid identification and differentiation of Pseudomonas aeruginosa clones from Canadian cystic fibrosis patients by capillary electrophoresis-mass spectrometry. We screened P. aeruginosa isolates for lipopolysaccharide structure and presence/absence of alginate and correlated these findings with antibiotic resistance patterns.

Background: Little is known about the combination of different medications in chronic obstructive pulmonary disease (COPD). This study determined the cost effectiveness of adding salmeterol (S) or fluticasone/salmeterol (FS) to tiotropium (T) for COPD., Methods: This concurrent, prospective, economic analysis was based on costs and health outcomes from a 52 week randomised study comparing: (1) T 18 microg once daily + placebo twice daily (TP group); (2) T 18 microg once daily + S 25 microg/puff, 2 puffs twice daily (TS group); and (3) T 18 microg once daily + FS 250/25 microg/puff, 2 puffs twice daily (TFS group). The incremental cost effectiveness ratios (ICERs) were defined as incremental cost per exacerbation avoided, and per additional quality adjusted life year (QALY) between treatments. A combination of imputation and bootstrapping was used to quantify uncertainty, and extensive sensitivity analyses were performed., Results: The average patient in the TP group generated CAN$2678 in direct medical costs compared with $2801 (TS group) and $4042 (TFS group). The TS strategy was dominated by TP and TFS. Compared with TP, the TFS strategy resulted in ICERs of $6510 per exacerbation avoided, and $243,180 per QALY gained. In those with severe COPD, TS resulted in equal exacerbation rates and slightly lower costs compared with TP., Conclusions: TFS had significantly better quality of life and fewer hospitalisations than patients treated with TP but these improvements in health outcomes were associated with increased costs. Neither TFS nor TS are economically attractive alternatives compared with monotherapy with T.

The recent Towards a Revolution in COPD Health (TORCH) randomised trial replicated the findings of previous trials in chronic obstructive pulmonary disease (COPD) on the apparent effectiveness of inhaled corticosteroids (ICS) in reducing exacerbation rates, but not so for mortality. In the present article, the authors review methodological issues in the TORCH and previous trials, such as patients already receiving ICS before randomisation and the absence of follow-up after study drug discontinuation, using data from two trials. First, among previous ICS users in the Canadian Optimal Therapy of COPD Trial, the hazard ratio of the first exacerbation with ICS relative to bronchodilators was 0.71 (95% confidence interval (CI) 0.53-0.96), while among those not using ICS prior to randomisation, it was 1.11 (95% CI 0.69-1.79). Secondly, the rate ratio of exacerbations with ICS was 0.78 (95% CI 0.61-0.99) prior to drug discontinuation during follow-up and 1.23 (95% CI 0.78-1.95) thereafter. Finally, a 2x2 factorial analysis of the TORCH data found a rate ratio of mortality for the salmeterol component to be 0.83 (95% CI 0.74-0.95), while for the fluticasone component it was 1.00 (95% CI 0.89-1.13). In conclusion, after proper consideration of the various methodological shortcomings in the design and analysis of randomised trials, the effectiveness of inhaled corticosteroids in treating chronic obstructive pulmonary disease remains doubtful, while the benefit observed with combination therapy may be due exclusively to the beneficial effects of the long-acting bronchodilator alone.

Background: Clinical trials measure exacerbations of chronic obstructive pulmonary disease (COPD) inconsistently. A study was undertaken to determine if different methods for ascertaining and analysing COPD exacerbations lead to biased estimates of treatment effects., Methods: Information on the methods used to count, analyse and report COPD exacerbation rates was abstracted from clinical trials of long-acting bronchodilators or long-acting bronchodilator/inhaled steroid combination products published between 2000 and 2006. Data from the Canadian Optimal Therapy of COPD Trial was used to illustrate how different analytical approaches can affect the estimate of exacerbation rates and their confidence intervals., Results: 22 trials (17,156 patients) met the inclusion criteria and were reviewed. None of the trials adjudicated exacerbations or determined independence of events. 14/22 studies (64%) introduced selection bias by not analysing outcome data for subjects who prematurely stopped study medications. Only 31% of trials used time-weighted analyses to calculate the mean number of exacerbations/patient-year and only 15% accounted for between-subject variation. In the Canadian Optimal Therapy of COPD Trial the rate ratio for exacerbations/patient-year was 0.85 when all data were included in a time-weighted analysis, but was overestimated as 0.79 when data for those who prematurely stopped study medications were excluded and was further overestimated as 0.46 when a time-weighted analysis was not conducted; p values ranged from 0.03 to 0.24 depending on how exacerbations were determined and analysed., Conclusions: Clinical trials have used widely different methods to define and analyse COPD exacerbations and this can lead to biased estimates of treatment effects. Future trials should strive to include blinded adjudication and assessment of the independence of exacerbation events, and trials should report time-weighted intention-to-treat analyses with adjustments for between-subject variation in COPD exacerbations.

Background: This study examined characteristics of adult and adolescent patients with cystic fibrosis (CF) to determine factors associated with an increased risk of pulmonary exacerbations., Methods: 249 patients with CF infected with multidrug resistant bacteria were recruited and prospectively followed for up to 4.5 years until they experienced a pulmonary exacerbation severe enough to require intravenous antibiotics. Multivariable regression analyses were used to compare the characteristics of patients who experienced an exacerbation with those who did not., Results: 124 of the 249 patients (50%) developed a pulmonary exacerbation during the first year and 154 (62%) experienced an exacerbation during the 4.5 year study period. Factors predictive of exacerbations in a multivariable survival model were younger age (OR 0.98, 95% CI 0.96 to 0.99), female sex (OR 1.45, 95% CI 1.07 to 1.95), lower forced expiratory volume in 1 second (FEV(1)) (OR 0.98, 95% CI 0.97 to 0.99), and a previous history of multiple pulmonary exacerbations (OR 3.16, 95% CI 1.93 to 5.17). Chronic use of inhaled corticosteroids was associated with an increased risk of exacerbation (OR 1.92, 95% CI 1.00 to 3.71) during the first study year., Conclusions: Patients who experience pulmonary exacerbations are more likely to be younger, female, using inhaled steroids, have a lower FEV(1), and a history of multiple previous exacerbations. It is hoped that knowledge of these risk factors will allow better identification and closer monitoring of patients who are at high risk of exacerbations.

The aim of the present study was to explore differences in the clinical expression, clinical diagnoses and management of airway diseases in a primary-care setting. Patients aged >or=35 yrs who had ever smoked were enrolled when they presented for any reason to one of eight rural primary-care practices. Respiratory symptom questionnaires and spirometry were administered. In total, 1,034 patients had acceptable and reproducible spirometry, of whom 550 (53%) were males and 484 (47%) were females. Males smoked more than females (41.2 versus 29.2 pack-yrs) respectively, and were more likely to have a pre-bronchodilator forced expiratory volume in one second/forced vital capacity <0.70 at 22.4 versus 11.8%, respectively. However, more females than males reported breathlessness (51.0 versus 42.8%, respectively), a prior diagnosis compatible with airflow obstruction and taking respiratory medications (23.4 versus 14.9%, respectively). In conclusion, the current results suggest that females are more likely than males to report breathlessness and be prescribed respiratory medications independent of differences in the severity of airflow obstruction.

Unlabelled: Spirometry has been reported to be under-utilized, and airflow obstruction may be under-diagnosed, in primary care practice., Study Objectives: The objective of this study was to determine the prevalence and severity of airflow obstruction in rural primary care settings and the degree to which it can be predicted by clinical characteristics. Spirometry was performed in patients 35 years and older who had smoked, presenting for any reason to one of eight rural primary care practices. Obstruction was defined as an FEV(1)/FVC<0.70. A total of 1046 subjects were recruited of whom 1034 had acceptable and reproducible spirometry. Airflow obstruction was detected in 17.4% (180 patients). Of those with obstruction, 77.2% (se 3.1%) had at least one respiratory symptom versus 62.4% (se 1.6%) without obstruction (P=0.0002). Only 44.9% (se 3.7%) of those with airflow obstruction had been previously diagnosed with obstructive lung disease. Of those with an FEV(1)<50% of predicted, 85% (se 5.6%) were breathless on exertion; however, only 63% (se 7.6%) were being treated with respiratory medications. We conclude that airflow obstruction is common in rural primary care practice and cannot be accurately predicted by symptoms. It is undiagnosed half of the time, and often not treated even when symptomatic.

Study Objective: To determine if screening spirometry in the primary care setting influences the physician's diagnosis and management of obstructive lung disease., Design: Diagnosis and management assessed before and after the intervention of screening spirometry., Participants: A total of 1,034 patients who had ever smoked and were at least 35 years of age presenting to primary care practices for any reason., Setting: Rural primary care practices., Measurements and Results: Physicians were asked prior to and following presentation of spirometry test results if they thought airflow obstruction was present and if they planned to change management based on the results. A new diagnosis of unsuspected airflow obstruction was made by the physician in 93 patients (9%), and a prior diagnosis of airflow obstruction was removed after spirometry in 115 patients (11%). After viewing the spirometry results, physicians reported that they would change patient management in 154 patients (15%). Most planned management changes occurred when airflow obstruction was newly diagnosed (57 of 93 patients, 61%) and when the diagnosis of airflow obstruction remained unchanged (80 of 195 patients, 41%). A 6-month chart review documented the addition of respiratory medications in 8% of patients., Conclusion: Screening spirometry influences physicians' diagnosis of airflow obstruction and management plans especially in patients with moderate-to-severe obstruction.

To assist patients with chronic obstructive pulmonary disease (COPD) in advance planning for life-threatening exacerbations, we developed a structured decision aid that describes the process, risks, and outcomes of intubation and mechanical ventilation (MV). Thirty-three patients with severe COPD took part in a before-after evaluation study. At baseline, only two participants (6%) reported that they had already made an advance decision about MV. After reviewing the decision aid, 31 participants (94%) reported that they had made a choice, which in 23 cases (74% of those deciding) was to forego MV. These choices were associated with more accurate expectations of MV outcome, and reduced decisional conflict. Qualitatively, participants who would accept MV emphasized their wish to prolong life, whereas those who would forego MV were more influenced by the burdens of treatment and the perception of a poor long-term outcome. However, there was evidence that 24% of participants did not completely comprehend the decision aid and 27% found the experience to be stressful. These findings indicate that a decision aid for MV helps patients plan for life-threatening exacerbations, and may be a useful adjunct to counseling for some patients with severe COPD.

The present authors hypothesised that bronchoscopy with protected specimen brush may sample biofilm-forming bacteria adherent to the airway wall, whereas traditional sputum collection may not. Pseudomonas aeruginosa obtained from sputum, bronchoalveolar lavage and protected brush, taken from the right upper lung bronchus of 12 adult patients with cystic fibrosis, were compared. Retrieved bacteria were genotyped, and grown in planktonic cultures and as biofilms, and susceptibilities to individual antibiotics and to antibiotic combinations were determined. Bacterial cultures obtained using bronchoscopy did not yield any new strains of bacteria that were not also found in sputum. A total of 10 patients (83%) had a single strain of P. aeruginosa found using sputum, bronchoalveolar lavage and protected brush techniques, and two patients (17%) had two strains recovered in sputum, but only one strain was recovered using bronchoscopic techniques. Susceptibility to single antibiotics and to antibiotic combinations were not different between planktonically or biofilm-grown bacteria derived from sputum, as compared to those obtained by bronchoalveolar lavage and protected brush. In conclusion, sputum collection provides as much information as bronchoscopy for characterising the genotype and antibiotic susceptibility of chronic Pseudomonas aeruginosa infection in patients with stable cystic fibrosis.

Background: Population-based studies have documented an association between obesity and an increased prevalence of asthma in women., Methods: We prospectively studied 58 obese women with a body mass index of > 30 kg/m(2), 24 of whom had asthma, who were enrolled in an intensive 6-month weight loss program to determine whether loss of body mass would be correlated with improvements in bronchial reactivity, lung function, and disease-specific health status., Results: Patients lost an average of 20 kg over the 6-month period. For every 10% relative loss of weight, the FVC improved by 92 mL (p = 0.05) and the FEV(1) improved by 73 mL (p = 0.04), however, bronchial reactivity did not significantly change with weight loss (p = 0.23). Patients who lost > 13% of their pretreatment weight experienced improvements in FEV(1) (p = 0.01), FVC (p = 0.02), and total lung capacity (p = 0.05) compared to patients in the lowest quartile who failed to lose significant amounts of weight. Neither group experienced any significant change in methacholine responsiveness (p = 0.57). Patients who completed the 6-month weight loss program experienced improvements in respiratory health status, irrespective of weight loss., Conclusion: We concluded that weight loss can improve lung function in obese women, however, the improvements appear to be independent of changes in airway reactivity.

Study Objective: We evaluate the accuracy, reliability, and potential impact of the National Emergency X-Radiography Utilization Study (NEXUS) low-risk criteria for cervical spine radiography, when applied in Canadian emergency departments (EDs)., Methods: The Canadian C-Spine Rule derivation study was a prospective cohort study conducted in 10 Canadian EDs that recruited alert and stable adult trauma patients. Physicians completed a 20-item data form for each patient and performed interobserver assessments when feasible. The prospective assessments included the 5 individual NEXUS criteria but not an explicit interpretation of the overall need for radiography according to the criteria. Patients underwent plain radiography, flexion-extension views, and computed tomography at the discretion of the treating physician. Patients who did not have radiography were followed up with a structured outcome assessment by telephone to determine clinically important cervical spine injury, a previously validated outcome measurement. Analyses included sensitivity and specificity with 95% confidence interval (CI), kappa coefficient, and potential radiography rates., Results: Among 8,924 patients, 151 (1.7%) patients had an important cervical spine injury. The combined NEXUS criteria identified important cervical spine injury with a sensitivity of 92.7% (95% CI 87% to 96%) and a specificity of 37.8% (95% CI 37% to 39%). Application of the NEXUS criteria would have potentially reduced cervical spine radiography rates by 6.1% from the actual rate of 68.9% to 62.8%. Of 11 patients with important injuries not identified, 2 were treated with internal fixation and 3 with a halo., Conclusion: This retrospective validation found the NEXUS low-risk criteria to be less sensitive than previously reported. The NEXUS low-risk criteria should be further explicitly and prospectively evaluated for accuracy and reliability before widespread clinical use outside of the United States.

The objective of this randomized, double-blind, placebo-controlled clinical trial was to determine whether a topical anesthetic agent (tetracaine) provides effective local analgesia prior to radial arterial puncture. Tetracaine or placebo gel was applied 45 min prior to arterial puncture to patients who were referred for elective arterial blood gas. The primary outcome was the patient's perception of pain associated with the procedure as measured by a visual analog scale. Fifty patients were randomized into the study, 24 received tetracaine and 26 placebo. Mean pain score on the visual analog scale was 26.2 +/- 32.6 for the tetracaine-treated patients and 23.8 +/- 27.4 for the placebo-treated patients (P = 0.78). Mean time from the first skin puncture to successful procurement of 1 ml of arterial blood was 70 +/- 103s in the tetracaine group and 49 +/- 48s in the placebo group (P = 0.40). Difficulty of arterial puncture as assessed by the respiratory therapist performing the test was identical for the two groups (P = 0.86). We conclude that tetracaine gel did not decrease patient's perception of pain associated with arterial puncture, nor did its use facilitate the ABG procedure.

Study Objectives: We compare the predictive accuracy of emergency physicians' unstructured clinical judgment to the Canadian C-Spine rule., Methods: This prospective multicenter cohort study was conducted at 10 Canadian urban academic emergency departments. Included in the study were alert, stable, adult patients with a Glasgow Coma Scale score of 15 and trauma to the head or neck. This was a substudy of the Canadian C-Spine and CT Head Study. Eligible patients were prospectively evaluated before radiography. Physicians estimated the probability of unstable cervical spine injury from 0% to 100% according to clinical judgment alone and filled out a data form. Interobserver assessments were done when feasible. Patients underwent cervical spine radiography or follow-up to determine clinically important cervical spine injuries. Analyses included comparison of areas under the receiver operating characteristic (ROC) curve with 95% confidence intervals (CIs) and the kappa coefficient., Results: During 18 months, 6265 patients were enrolled. The mean age was 36.6 years (range 16 to 97 years), and 50.1% were men. Sixty-four (1%) patients had a clinically important injury. The physicians' kappa for a 0% predicted probability of injury was 0.46 (95% CI 0.28 to 0.65). The respective areas under the ROC curve for predicting cervical spine injury were 0.85 (95% CI 0.80 to 0.89) for physician judgment and 0.91 (95% CI 0.89 to 0.92) for the Canadian C-Spine rule (P <.05). With a threshold of 0% predicted probability of injury, the respective indices of accuracy for physicians and the Canadian C-Spine rule were sensitivity 92.2% versus 100% (P <.001) and specificity 53.9% versus 44.0% (P <.001)., Conclusion: Interobserver agreement of unstructured clinical judgment for predicting clinically important cervical spine injury is only fair, and the sensitivity is unacceptably low. The Canadian C-Spine rule was better at detecting clinically important injuries with a sensitivity of 100%. Prospective validation has recently been completed and should permit widespread use of the Canadian C-Spine rule.

Study Objective: To determine whether currently available measurement tools can be used to obtain valid measurements of short-term changes in dyspnea and disease-specific quality of life (QOL) in outpatients with an acute COPD exacerbation., Design: Prospective cohort study., Methods: Sixty-six patients with an acute COPD exacerbation who presented to the emergency department completed the chronic respiratory disease index questionnaire (CRQ) and the baseline dyspnea index (BDI) and were discharged home receiving 10 days of medical therapy. Reassessment with the CRQ and the transitional dyspnea index (TDI) occurred within 48 h of relapse (defined as an urgent hospital revisit within 10 days because of worsening respiratory symptoms), or 10 days later if relapse did not occur., Results: Patients who did not relapse (n = 49) showed moderate-to-large improvements in disease-specific QOL across all four CRQ domains (improvements in each domain of 1.4 to 1.9 U; p < 0.001 for all domains) and large positive changes in the TDI (total TDI score, + 5.02 plus minus 0.55 U; p = 0.0001). In contrast, patients who had a relapse (n = 17) did not have improved CRQ or TDI scores (mean negative change in three of four CRQ domains, total TDI score - 3.06 plus minus 1.14 U; p = 0.02). Changes in the CRQ dyspnea score and TDI correlated with each other (r = 0.78; p = 0.0001) and with changes in FEV(1) (CRQ, r = 0.48 and p = 0.0001; TDI, r = 0.46 and p = 0.0002). Ten control patients with stable COPD showed no changes in the CRQ or TDI over 10 days., Conclusion: The CRQ and BDI/TDI can be used to obtain valid, responsive measures of acute changes in QOL and dyspnea associated with a COPD exacerbation. The direction and magnitude of change in these scores was highly correlated with clinical outcome and with other health measures. Most outpatients treated for a COPD exacerbation experience significant short-term improvements in QOL and dyspnea, with the exception of patients who have a clinical relapse of symptoms.

Context: High levels of variation and inefficiency exist in current clinical practice regarding use of cervical spine (C-spine) radiography in alert and stable trauma patients., Objective: To derive a clinical decision rule that is highly sensitive for detecting acute C-spine injury and will allow emergency department (ED) physicians to be more selective in use of radiography in alert and stable trauma patients., Design: Prospective cohort study conducted from October 1996 to April 1999, in which physicians evaluated patients for 20 standardized clinical findings prior to radiography. In some cases, a second physician performed independent interobserver assessments., Setting: Ten EDs in large Canadian community and university hospitals., Patients: Convenience sample of 8924 adults (mean age, 37 years) who presented to the ED with blunt trauma to the head/neck, stable vital signs, and a Glasgow Coma Scale score of 15., Main Outcome Measure: Clinically important C-spine injury, evaluated by plain radiography, computed tomography, and a structured follow-up telephone interview. The clinical decision rule was derived using the kappa coefficient, logistic regression analysis, and chi(2) recursive partitioning techniques., Results: Among the study sample, 151 (1.7%) had important C-spine injury. The resultant model and final Canadian C-Spine Rule comprises 3 main questions: (1) is there any high-risk factor present that mandates radiography (ie, age >/=65 years, dangerous mechanism, or paresthesias in extremities)? (2) is there any low-risk factor present that allows safe assessment of range of motion (ie, simple rear-end motor vehicle collision, sitting position in ED, ambulatory at any time since injury, delayed onset of neck pain, or absence of midline C-spine tenderness)? and (3) is the patient able to actively rotate neck 45 degrees to the left and right? By cross-validation, this rule had 100% sensitivity (95% confidence interval [CI], 98%-100%) and 42.5% specificity (95% CI, 40%-44%) for identifying 151 clinically important C-spine injuries. The potential radiography ordering rate would be 58.2%., Conclusion: We have derived the Canadian C-Spine Rule, a highly sensitive decision rule for use of C-spine radiography in alert and stable trauma patients. If prospectively validated in other cohorts, this rule has the potential to significantly reduce practice variation and inefficiency in ED use of C-spine radiography.