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Emma R McIvor,1 R Andrew McIvor2 1Queen’s University, Belfast, UK; 2Department of Medicine, McMaster University, Firestone Institute for Respiratory Health, Hamilton, Ontario, Canada Abstract: Tiotropium is a long-acting muscarinic antagonist (LAMA) that exerts its bronchodilatory effect by blocking endogenous acetylcholine receptors in the airways. Its safety and efficacy are well established for the treatment of COPD, and it is now being recognized for its role in improving lung function and control in asthma. This review discusses the evolving role of tiotropium delivered by the Respimat® in patients across the range of asthma severities and ages, and provides an overview of safety and efficacy data. Tiotropium is the only LAMA currently approved for the treatment of asthma, and evidence from a large-scale clinical trial program, including several Phase III studies in adults, has demonstrated that tiotropium improves lung function and asthma control, with a safety profile comparable with that of placebo. Clinical trials in adolescent patients (aged 12–17 years) have also shown improvements in lung function and trends toward improved asthma control. Of note, the efficacy and safety profiles are consistent regardless of baseline characteristics and phenotype. Given the large and growing body of evidence, it is likely that as clinical experience with tiotropium increases, this treatment may possibly emerge as the key choice for add-on therapy to inhaled corticosteroids/long-acting β2-agonists, and in patients who do not tolerate long-acting bronchodilators or other medications, in the future. Keywords: tiotropium, anticholinergics, asthma, efficacy

Neil W Johnston,1 Marita Olsson,2 Staffan Edsbäcker,3 Maria Gerhardsson de Verdier,4 Per Gustafson,5 Christopher McCrae,3 Peter V Coyle,6 R Andrew McIvor11Department of Medicine, Firestone Institute for Respiratory Health, McMaster University, Hamilton, ON, Canada; 2Early Clinical Development Biometrics, 3Respiratory, Inflammation & Autoimmunity Unit, Innovative Medicines & Early Development, 4Medical Evidence and Observational Research Centre, 5Respiratory, Inflammation & Autoimmunity Translational Medicine Unit, Early Clinical Development, Innovative Medicines & Early Development, AstraZeneca Research and Development, Gothenburg, Molndal, Sweden; 6Regional Virology Laboratory, Belfast HS C Trust, Belfast, UKRationale: Common colds are associated with acute respiratory symptom exacerbations in COPD patients.Objective: To determine exacerbation risk and severity in COPD patients with/without coincident self-reported colds.Methods: Global initiative for chronic Obstructive Lung Disease stage I–IV COPD patients electronically transmitted respiratory symptom diaries to research staff daily between December 2006 and April 2009. Respiratory symptom worsening prompted contact by a study nurse and patient assessment to determine if a cold was present or an exacerbation underway. A composite daily symptom score was derived for each subject from diarized symptom data. The exacerbation/cold/virus relation was examined using a Poisson regression model, the relation of colds to respiratory symptom severity using generalized estimating equation models.Results: Daily diary transmission compliance of >97% enabled detection of all possible exacerbations. Among 262 exacerbations meeting Anthonisen criteria, 218 (83%) had cold-like symptoms present at their inception, but respiratory viruses were detected in only 106 (40%). Within-subject exacerbation risk was 30 times (95% confidence interval [CI]: 20, 47; P

Objective: The objectives of our study were to compare patient characteristics and severity of disease in obese and normal-weight-confirmed people with asthma and to explore reasons for misdiagnosis of asthma, including potential interactions with obesity.Methods: We randomly selected patients with physician-diagnosed asthma from eight Canadian cities. Asthma diagnosis was confirmed via a sequential lung function testing algorithm. Logistic analysis was conducted to compare obese and normal-weight-confirmed people with asthma and to assess characteristics associated with misdiagnosis of asthma. Interaction with obesity was investigated.Results: Complete assessments were obtained on 496 subjects who reported physician-diagnosed asthma (242 obese and 254 normal-weight subjects); 346 had asthma confirmed with sequential lung testing, and in 150 subjects a diagnosis of asthma was ruled out. Obese subjects with asthma were significantly more likely to be men, have a history of hypertension and gastroesophageal reflux disease, and have a lower FEV(1) compared with normal-weight subjects with asthma. Older subjects, men, and subjects with higher FEV(1) were more likely to have received misdiagnoses of asthma. Obesity was not an independent predictor of misdiagnosis, however there was an interaction between obesity and urgent visits for respiratory symptoms. The odds ratio for receiving a misdiagnosis of asthma for obese individuals as compared with normal-weight individuals was 4.08 (95% CI, 1.23-13.5) for those with urgent visits in the past 12 months.Conclusions: Obese people with asthma have lower lung function and more comorbidities compared with normal-weight people with asthma. Obese individuals who make urgent visits for respiratory symptoms are more likely to receive a misdiagnosis of asthma. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is a common disorder with a high prevalence among elderly men and women and an increasing mortality rate. Its diagnosis relies on spirometry, with a diagnostic cut-off value of a forced expiratory volume in 1 second (FEV1)/forced vital capacity ratio of <0.7. This cut-off level has received some criticism because a ratio decline is part of normal advanced aging. Thus, clinicians must be vigilant in applying appropriate diagnostic criteria when managing elderly patients and may choose to use one or more of the alternative diagnostic values that have been created. It is important to remember that COPD is a systemic disorder with several extrapulmonary manifestations. Elderly patients with COPD are at an increased risk of cardiovascular events, osteoporosis, fractures, peripheral muscle wasting, depression and anxiety. Management of these patients requires a multidisciplinary approach and should begin with stratification of disease severity and prognostic information for each patient. Traditionally, FEV1 has been used as a marker of COPD severity. However, indices such as the Modified Medical Research Council (MMRC) Dyspnoea Scale; the updated body mass, airflow, obstruction, dyspnoea and exercise (BODE) index; and the new age, dyspnoea, obstruction (ADO) index have been found to be better predictors of mortality in elderly patients. In addition to smoking cessation, supplemental oxygen and vaccines, management strategies such as patient education programmes - which have been shown to reduce hospital admissions -- should not be overlooked. Pulmonary rehabilitation remains an underutilized treatment modality despite its demonstrated association with improvements in quality of life, reduced dyspnoea and increased exercise capacity. Studies have shown no correlation between age and outcomes in pulmonary rehabilitation, suggesting that age should not be an exclusion criterion. Although bronchodilators and corticosteroids remain the cornerstone of pharmaceutical management of COPD, their efficacy relies on correct medication administration. Inhaler technique should be frequently assessed in the elderly population and the choice of inhaler device needs to be tailored to the patients' needs, situation and preferences. Assessment and management of extrapulmonary co-morbidities of COPD should also be undertaken. Careful attention to the mental health of elderly patients with COPD is also vital, as they have high rates of depression and anxiety. Furthermore, elderly patients with severe COPD receive inadequate palliative care despite the elevated mortality risk associated with this illness. Early discussion about end-of-life care and advanced care planning is recommended. [ABSTRACT FROM AUTHOR]

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]

Objective: To review the diagnosis, assessment of severity, and management of chronic obstructive pulmonary disease (COPD) and to address the systemic manifestations associated with COPD.Sources Of Information: PubMed was searched from January 2000 to December 2007 using the key words COPD, practice guidelines, randomized controlled trials, therapy, and health outcomes. The Canadian Thoracic Society guideline on management of COPD was carefully reviewed. The authors, who have extensive experience in care of patients with COPD, provided expert opinion.Main Message: Chronic obstructive pulmonary disease is a common systemic disease caused primarily by smoking. Spirometry is essential for diagnosis of COPD and should be integrated into primary care practice. Pharmacologic and nonpharmacologic therapy improves symptoms, capacity for exercise, and quality of life. Smoking cessation is the only intervention shown to slow disease progression. The systemic manifestations and comorbidity associated with COPD need to be identified and addressed to optimize health and quality of life.Conclusion: An evidence-based approach to managing COPD along with a primary care chronic disease management model could improve quality of life for patients with COPD. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine whether asthma control in Canada had improved since the last major survey in 1999 by exploring how well patients' asthma was controlled, how much they knew about asthma control, and how they used health care resources.DESIGN: National telephone survey of patients between April and August 2004.SETTING: Canada.PARTICIPANTS: Eight hundred ninety-three adults 18 to 54 years old diagnosed with asthma more than 6 months before the survey.MAIN OUTCOME MEASURES: Patients' control of their asthma, patients' knowledge about asthma, the frequency and duration of periods of worsening asthma, and patients' use of health care resources to manage those periods.RESULTS: In total, 26 210 households listed in a consumer database were contacted. Excluding ineligible households and households with a language barrier, a member of 13% of the households completed the 35-minute survey. Based on definitions in Canadian guidelines, 53% of patients had symptomatic uncontrolled asthma. In the previous year, almost all asthma patients had experienced worsening of symptoms that lasted on average 13.6 days for patients with uncontrolled asthma and 8.0 days for patients with controlled asthma (P < .02). Markedly more patients with uncontrolled asthma used health care resources for episodes of asthma than patients with controlled asthma did (72% vs 15% for urgent office visits, P < .01; 32% vs 3% for emergency department visits, P < .01; and 7% vs 0% for hospitalizations, P < .01) in the year before the survey. Patients were confused about the differences between reliever and controller medications. One third of patients claimed that no one had taught them about asthma medications, and one quarter said they had received no training on how to recognize the early signs of asthma worsening.CONCLUSION: Asthma control and management remained suboptimal in Canada and relatively unchanged since the previous major survey in 1999. [ABSTRACT FROM AUTHOR]

In a prospective, multicentre double-blind trial, 151 patients over the age of 65 years were randomly assigned to receive either cefepime 2 g every 12 h for a minimum of 3 days and up to 14 days or ceftriaxone 1 g every 12 h for a minimum of 3 days and up to 14 days. Antibiotics were maintained until 48 h after fever had resolved; no other antibiotics were permitted. The average age in each group exceeded 77 years and significant co-morbidity was found in the majority of patients. The mean total duration of therapy was 5.8 ± 2.4 days for the cefepime group and 6.7 ± 2.7 days for the ceftriaxone group (P=0.06). The clinical success rate at the end of therapy was 79.1% with cefepime and 75.4% with ceftriaxone (P=0.62). At the end of follow-up, 91.7% of the cefepime-treated patients and 86.5% of the ceftriaxone patients had a satisfactory clinical response (P=0.38). In 35 bacteriological evaluable patients, potential pathogens were eradicated in all but one patient receiving cefepime. Seven patients in each group died during the study period but in each case the death was unrelated to study drug. The commonest side-effect was diarrhoea (cefepime, five patients; ceftriaxone, two patients). The clinical and microbiological efficacy of cefepime is similar to that of ceftiaxone in elderly patients with community-acquired pneumonia requiring hospitalization. Cefepime is an appropriate choice for the treatment of community-acquired respiratory tract infections in the elderly. [ABSTRACT FROM PUBLISHER]

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: 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: 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: 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.

Valved holding chambers (VHCs) have been used with pressurized metered-dose inhalers since the early 1980s. They have been shown to increase fine particle delivery to the lungs, decrease oropharyngeal deposition, and reduce side effects such as throat irritation, dysphonia, and oral candidiasis that are common with use of pressurized metered-dose inhalers (pMDIs) alone. VHCs act as aerosol reservoirs, allowing the user to actuate the pMDI device and then inhale the medication in a two-step process that helps users overcome challenges in coordinating pMDI actuation with inhalation. The design of VHC devices can have an impact on performance. Features such as antistatic properties, effective face-to-facemask seal feedback whistles indicating correct inhalation speed, and inhalation indicators all help improve function and performance, and have been demonstrated to improve asthma control, reduce the rate of exacerbations, and improve quality of life. Not all VHCs are the same, and they are not interchangeable. Each pairing of a pMDI device plus VHC should be considered as a unique delivery system.

Asthma is a chronic disease of airway inflammation with a large global burden. Despite established, guideline-based stepwise therapy, a significant proportion of patients remain symptomatic and poorly controlled. As such, there is a need for additional safe, effective, convenient, and cost-effective therapies that can be broadly applied across a range of asthma phenotypes. Tiotropium is a long-acting muscarinic antagonist (LAMA) that leads to bronchodilation by blocking endogenous acetylcholine receptors in the airways. Tiotropium has long been approved for the treatment of chronic obstructive pulmonary disease, and it has recently been recognized for its safety and efficacy in improving lung function and controlling asthma. Evidence from several Phase III trials in the adult and paediatric population has shown that tiotropium is well tolerated and significantly improves a range of endpoints as an add-on treatment to ICS therapy, regardless of baseline characteristics and clinical phenotypes. Consequently, regulatory authorities worldwide have recently licensed tiotropium as the only LAMA approved for the treatment of asthma. This review provides an overview of safety and efficacy data and discusses the use of tiotropium in patients across the range of asthma severities, ages, and phenotypes.

Background: Healthcare systems are under increasing strain, predominantly due to chronic non-communicable diseases. Connected healthcare technologies are becoming ever more capable and their components cheaper. These innovations could facilitate both self-management and more efficient use of healthcare resources for common respiratory diseases such as asthma and chronic obstructive pulmonary disease. However, newer technologies can only facilitate major changes in practice, and cannot accomplish them in isolation., Focus of Review: There are now large numbers of devices and software offerings available. However, the potential of such technologies is not being realised due to limited engagement with the public, clinicians and providers, and a relative paucity of evidence describing elements of best practice in this complex and evolving environment. Indeed, there are clear examples of wasted resources and potential harm. We therefore call on interested parties to work collaboratively to begin to realize the potential benefits and reduce the risks of connected technologies through change in practice. We highlight key areas where such partnership can facilitate the effective and safe use of technology in chronic respiratory care: developing data standards and fostering inter-operability, making collaborative testing facilities available at scale for small to medium enterprises, developing and promoting new adaptive trial designs, developing robust health economic models, agreeing expedited approval pathways, and detailed planning of dissemination to use., Conclusion: The increasing capability and availability of connected technologies in respiratory care offers great opportunities and significant risks. A co-ordinated collaborative approach is needed to realize these benefits at scale. Using newer technologies to revolutionize practice relies on widespread engagement and cannot be delivered by a minority of interested specialists. Failure to engage risks a costly and inefficient chapter in respiratory care., Competing Interests: Disclosure RWC has a patent on the use of acoustic analysis to assess inhaler use. DP has previously had research funding to develop software to assess inhaler technique. The other authors report no conflicts of interest in this work.

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.

Objective: Asthma is a chronic inflammatory disorder of the airways with increasing worldwide prevalence. Despite treatment according to guidelines, a considerable proportion of patients with asthma remain symptomatic. Different potential therapeutic options for the treatment of these patients are currently in development and undergoing clinical trials, and it is important to regularly review their status., Data Sources: A search of ClinicalTrials.gov was performed and supported by a PubMed literature search and restricted to the previous 10 years to ensure currency of data. The results were manually filtered to identify relevant articles., Study Selections: Emerging therapies that are currently in phase 2 and 3 development include anti-interleukin agents (benralizumab, reslizumab, dupilumab, brodalumab, lebrikizumab, and mepolizumab), a chemoattractant receptor-homologous molecule expressed on a T-helper type 2 lymphocyte antagonist (OC000459), a phosphodiesterase-4 inhibitor (roflumilast), and long-acting muscarinic antagonists (glycopyrronium bromide, umeclidinium bromide, and tiotropium bromide)., Results: The clinical trial program of the long-acting muscarinic antagonist tiotropium is currently the most advanced, with data available from different phase 2 and 3 studies. Results demonstrate that it is an efficacious add-on to at least inhaled corticosteroid maintenance therapy across severities of symptomatic asthma., Conclusion: The results of ongoing and future studies will help to determine whether these emerging therapeutic options will help address the unmet need for improvement in asthma management., (Copyright © 2015 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Research in respiratory, sleep, and critical care medicine has historically been the domain of scientists and clinicians attempting to understand pathophysiological mechanisms and consequences of disease in an effort to develop effective treatments. This traditional approach of placing scientific rigor before the patient's reality is changing. There is growing recognition of the importance of integrating patient perspectives (e.g., preferences, expectations, and expanded definitions of what constitutes "successful" outcomes) into clinical research to achieve meaningful results for a broader group of stakeholders. This evolution is reflected in the growth of patient-centered organizations and patient advocacy groups that seek to meaningfully integrate patients into the process of prioritizing research needs and creating alliances wherein patients and researchers can partner together to accomplish research goals. In tandem, a growing number of real-world trials (i.e., those with broader, more representative patient populations and routine care pathways) now complement findings from traditional randomized controlled trials and offer new opportunities to design studies that better reflect patients' healthcare preferences and experiences. Patients' perspectives are key determinants of treatment adherence and outcomes, as well as the feasibility and likely value of implementing care pathways. The advent of smartphone and push technologies offer new opportunities for the collection of more patient-centered and ecologically valid patient data, thereby adding new dimensions to meaningfully integrate patients into real-world research.

Background: Paper-based diaries and self-report of symptom worsening in COPD may lead to underdetection of exacerbations. Epidemiologically, COPD exacerbations exhibit seasonal patterns peaking at year-end. We examined whether the use of a BlackBerry-based daily symptom diary would detect 95% or more of exacerbations and enable characterization of seasonal differences among them., Methods: Fifty participants with GOLD (Global Initiative for Chronic Obstructive Lung Disease) stage I to IV COPD began a community-based study in December 2007. Another 30 began in December 2008. Participants transmitted daily symptom diaries using a BlackBerry. Alerts were triggered when symptom changes, missed diary transmissions, or medical care for a respiratory problem occurred. Participant encounters were initiated if COPD exacerbations were suspected. Participants used their BlackBerrys to report returns to normal breathing., Results: Participants transmitted 99.9% of 28,514 possible daily diaries. All 191 (2.5/participant-year) COPD exacerbations meeting Anthonisen criteria were detected. During 148 of the 191 exacerbations (78%, 1.97/participant-year), patients were hospitalized and/or ordered prednisone, an antibiotic, or both. Respiratory viruses were detected in 78 of the 191 exacerbations (41%). Those coinciding with a respiratory viral infection averaged 12.0 days, and those without averaged 8.9 days (P &lt; .04), with no difference in Anthonisen score. Respiratory symptom scores before exacerbations and after normal breathing return showed no differences. Exacerbations were more frequent during the Christmas period than the rest of the year but were not more frequent than in the rest of winter alone., Conclusions: Smartphone-based collection of COPD symptom diaries enables near-complete identification of exacerbations at inception. Exacerbation rates in the Christmas season do not reach levels that necessitate changes in disease management.

Frequent exacerbations of COPD are associated with accelerated loss of lung function, declining health status, increased mortality, and increased health care costs. Thus, a key objective in the management of COPD is preventing exacerbations or at least reducing their number and severity. When new interventions are examined, their value is sometimes assessed in reference to the minimal clinically important difference (MCID), a theoretical construct that may be defined and estimated numerically in several different ways. There have been limited attempts to calculate the MCID for COPD exacerbations but a figure of 20% reduction in exacerbation frequency is occasionally cited as the "established" MCID from a single manuscript reviewing six clinical trials. Our review suggests that defining and calculating the MCID for COPD exacerbations is problematic, not only because the methodology around developing endpoints for MCIDs is inconsistent, but because the impact of exacerbation reduction is likely to be influenced dramatically by the definitions of exacerbation severity used and the population's baseline status. Reference to current literature shows that at least one other estimate for exacerbation MCID as low as 4%. MCID is sometimes estimated by expert consensus; a review of articles used to shape COPD guidelines shows frequent reference to articles in which interventions yielded exacerbation differences as low as 11%. We find no evidence of an established MCID but suggest that interventions reducing exacerbations by as little as 11% appear to be regarded widely as clinically important.

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality worldwide. Although considerable advances have been made in the diagnosis and treatment of COPD, much remains to be done both to alleviate symptoms and reduce mortality associated with this condition. Previously, diagnosis, management, and research all centred on staging based on the forced expiratory flow in 1 second. It is now becoming apparent that this is inadequate to truly capture current disease burden and future deterioration. Fortunately, new approaches to care are constantly being identified. It is now known that symptoms and, in particular, exacerbations represent pivotal events in the patient's life that should trigger optimization of care. Much work is currently underway to identify various phenotypes in COPD because it has become obvious that this is a heterogeneous disease and applying the same management algorithms for all patients is insufficient. Several new medications are at various stages of development, some being approved and on the market, while others are undergoing clinical trials. These allow for more options for individualized care of patients. In addition, new applications of old medications, such as long‑term antibiotics, also provide new options for patients struggling with recurrent symptoms. Finally, the growing awareness that this is a heterogeneous disease composed not only of differing phenotypes but also having significant extrapulmonary comorbidities have opened new avenues of research and interdisciplinary collaboration that will further enable us to offer personalized care to patients.

Mucinous bronchioloalveolar carcinoma (BAC) can be associated with significant bronchorrhea. A 46-year-old man presented with BAC with 2,000 mL of sputum production on a daily basis, which prevented him from being extubated. As this condition is rare, there are only case reports outlining the therapy for the associated bronchorrhea. We used azithromycin, scopolamine, and inhaled fluticasone with moderate success. The initiation of an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, gefitinib, resulted in dramatic improvement in the volume of pulmonary secretions produced. The patient's EGFR mutation status was subsequently found to be negative, which supports the hypothesis that the mechanism of reduction of bronchorrhea is independent of the antiproliferative effect of the drug.

Background: Chronic obstructive pulmonary disease (COPD) and asthma are common; however, mortality rates among individuals with these diseases are not well studied in North America., Objective: To investigate mortality rates and risk factors for premature death among subjects with COPD., Methods: Subjects were identified from the lung function testing databases of two academic respiratory disease clinics in Hamilton and Toronto, Ontario. Mortality was ascertained by linkage to the Ontario mortality registry between 1992 and 2002, inclusive. Standardized mortality ratios were computed. Poisson regression of standardized mortality ratios and proportional hazards regression were performed to examine the multivariate effect of risk factors on the standardized mortality ratios and mortality hazards., Results: Compared with the Ontario population, all-cause mortality was approximately doubled among subjects with COPD, but was lower than expected among subjects with asthma. The risk of mortality in patients with COPD was related to cigarette smoking, to the presence of comorbid conditons of ischemic heart disease and diabetes, and to Global initiative for chronic Obstructive Lung Disease severity scores. Individuals living closer to traffic sources showed an elevated risk of death compared with those who lived further away from traffic sources., Conclusions: Mortality rates among subjects diagnosed with COPD were substantially elevated. There were several deaths attributed to asthma among subjects in the present study; however, overall, patients with asthma demonstrated lower mortality rates than the general population. Subjects with COPD need to be managed with attention devoted to both their respiratory disorders and related comorbidities.

Introduction: Asthma is a complex process that results from airway inflammation and manifests as bronchoconstriction. Infiltration of the airway mucosa and lumen by activated inflammatory cells, along with release of mediators, can occur extensively. Chemical mediators known as leukotrienes are believed to play a major role in this process. At present, inhaled corticosteroids (ICS) are the pharmacologic cornerstone of asthma management. However, asthma control may remain suboptimal when relying on ICS because of problems with compliance, poor inhaler technique and concerns about the side effects of steroids; additional agents are often required to control symptoms. Leukotriene receptor antagonists (LTRA), namely montelukast, provide a safe and effective additional anti-inflammatory treatment option. There is particular benefit for patients with asthma and concomitant allergic rhinitis., Areas Covered: Montelukast has been well studied through rigorous clinical trials. A thorough review of the literature has been undertaken to assess the evidence supporting the use of LTRAs. This review focuses on the role of montelukast not only as monotherapy but also as add-on therapy to ICS in the adult asthma population, as well as adult asthmatics with concomitant allergic rhinitis. In addition, there is often some discrepancy between the evidence generated in the idealized asthma patients recruited into randomized clinical trials and results obtained in the real-life setting. This review assesses recent clinical trials evaluating the real-life evaluation of montelukast, achieved mainly through open-label observational studies., Expert Opinion: Oral LTRA bring remarkable ease of anti-inflammatory treatment administration and symptom improvement with minimal side effects to the management of adult asthma. Basic asthma mechanisms and much-valued scientific groundwork has been identified by exploring target asthma treatment with anti-leukotriene therapy. This will have a significant impact in the future development of targeted asthma therapies as well as the current management of asthma and other inflammatory medical conditions.

Introduction: Chronic obstructive pulmonary disease (COPD) is a disease state characterised by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases. Classically, it is thought to be a combination of emphysema and chronic bronchitis, although only one of these may be present in some people with COPD. The main risk factor for the development and deterioration of COPD is smoking., Methods and Outcomes: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of maintenance drug treatment in stable COPD? What are the effects of smoking cessation interventions in people with stable COPD? What are the effects of non-drug interventions in people with stable COPD? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA)., Results: We found 119 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions., Conclusions: In this systematic review, we present information relating to the effectiveness and safety of the following interventions: alpha(1) antitrypsin, antibiotics (prophylactic), anticholinergics (inhaled), beta(2) agonists (inhaled), corticosteroids (oral and inhaled), general physical activity enhancement, inspiratory muscle training, nutritional supplementation, mucolytics, oxygen treatment (long-term domiciliary treatment), peripheral muscle strength training, psychosocial and pharmacological interventions for smoking cessation, pulmonary rehabilitation, and theophylline.

Triple therapy for COPD consists of a long-acting anti-cholinergic bronchodilator, a long-acting beta-agonist bronchodilator, and an inhaled corticosteroid. Guidelines from the Canadian Thoracic Society advocate triple therapy for some patients with moderate-to-severe COPD. The objective of this review was to evaluate the evidence based clinical efficacy of triple therapy compared to dual bronchodilator therapy (long-acting anti-cholinergic bronchodilator + beta-agonist bronchodilator) or long-acting anti-cholinergic bronchodilator monotherapy for managing COPD. A systematic literature search was conducted to identify relevant clinical evaluations of triple therapy in the management of moderate to severe COPD. Databases searched included: Medline; EMBASE; CINAHL and PubMed (non-Medline records only). Of 2,314 publications, 4 articles evaluated triple therapy for the management of COPD. Hospitalization rates for COPD exacerbations, reported in 2 trials, were significantly reduced with triple therapy compared to long-acting anti-cholinergic bronchodilator monotherapy, with reported relative risks of 0.53 (95% CI: 0.33, 0.86, p = 0.01) and 0.35 (95% CI: 0.16-0.78, p = 0.011). Exacerbation data is inconsistent between the two trials reporting this outcome. Lung function, dyspnea and quality of life data show statistical significant changes with triple therapy compared to long-acting anti-cholinergic bronchodilator monotherapy but the changes do not reach clinical importance. Triple therapy does decrease the number of hospitalizations for severe/acute COPD exacerbations compared with long-acting anti-cholinergic bronchodilator monotherapy. There is insufficient evidence to determine if triple therapy is superior to dual bronchodilator therapy.

Asthma is a complex process involving extensive infiltration of the airway mucosa and lumen by activated inflammatory cells and release of mediators that result in airway inflammation and bronchoconstriction. Leukotrienes are mediators believed to play a major role in this process. At present, inhaled corticosteroids are the cornerstone of asthma management. However, asthma control may remain suboptimal and there is well-documented concern regarding adverse events with the use of inhaled corticosteroids in children. Leukotriene receptor antagonists, such as montelukast, provide a safe and effective treatment option with ease of administration, particularly in preschool children and as add-on therapy in patients with difficult-to-control asthma.

Background: Blood cultures (BC) are commonly ordered during the initial assessment of patients with community-acquired pneumonia (CAP), yet their yield remains low. Selective use of BC would allow the opportunity to save healthcare resources and avoid patient discomfort. The study was to determine what demographic and clinical factors predict a greater likelihood of a positive blood culture result in patients diagnosed with CAP., Methods: A structured retrospective systematic chart audit was performed to compare relevant demographic and clinical details of patients admitted with CAP, in whom blood culture results were positive, with those of age, sex, and date-matched control patients in whom blood culture results were negative., Results: On univariate analysis, eight variables were associated with a positive BC result. After logistic regression analysis, however, the only variables statistically significantly associated with a positive BC were WBC less than 4.5 × 10(9)/L [likelihood ratio (LR): 7.75, 95% CI=2.89-30.39], creatinine >106 μmol/L (LR: 3.15, 95%CI=1.71-5.80), serum glucose<6.1 mmol/L (LR: 2.46, 95%CI=1.14-5.32), and temperature > 38 °C (LR: 2.25, 95% CI =1.21-4.20). A patient with all of these variables had a LR of having a positive BC of 135.53 (95% CI=25.28-726.8) compared to patients with none of these variables., Conclusions: Certain clinical variables in patients with CAP admitted to hospitals do appear to be associated with a higher probability of a positive yield of BC, with combinations of these variables increasing this likelihood. We have identified a subgroup of CAP patients in whom blood cultures are more likely to be useful.