Benralizumab for allergic asthma: a randomised, double-blind, placebo-controlled, trial.

RATIONALE AND OBJECTIVE: Benralizumab induces rapid and near-complete depletion of eosinophils from blood and lung tissue. We investigated whether benralizumab could attenuate allergen-induced late asthmatic responses (LAR) in participants with allergic asthma. METHODS AND MEASUREMENTS: Participants with allergic asthma who demonstrated increased sputum eosinophils and LAR at screening were randomised to benralizumab 30 mg or matched placebo given every 4 weeks for 8 weeks (3 doses). Allergen challenges were performed at weeks 9 and 12 when blood, sputum, bone marrow and bronchial tissue eosinophils and LAR were assessed. MAIN RESULTS: Forty-six participants (mean age, 30.9 years) were randomised to benralizumab (n = 23) or placebo (n = 23). Eosinophils were significantly reduced in the benralizumab group compared with placebo in blood at 4 weeks and sputum and bone marrow at 9 weeks after treatment initiation. At 7 h after an allergen challenge at week 9, sputum eosinophilia was significantly attenuated in the benralizumab group compared to placebo (least squares mean difference -5.81% [95% CI, -10.69, -0.94]; P = 0.021); however, the LAR was not significantly different (least squares mean difference 2.54% [95% CI, 3.05, 8.12]; P = 0.363). Adverse events were reported for 7 (30.4%) and 14 (60.9%) participants in the benralizumab and placebo groups, respectively. CONCLUSION: Benralizumab administration over 8 weeks resulted in a significant attenuation of blood, bone marrow and sputum eosinophilia in participants with mild allergic asthma; however, there was no change in the LAR, suggesting that eosinophils alone are not a key component of allergen-induced bronchoconstriction.

Access to Treatment for Chronic Obstructive Pulmonary Disease (COPD) in the Americas: A Call for Action.

Chronic obstructive pulmonary disease (COPD) is a major public health problem in the Americas (a region of the world comprising North, Central, and South America), though there is substantial variation in disease prevalence, morbidity and mortality between and within nations. Across the Americas, COPD disproportionately affects vulnerable populations including minoritized populations and impoverished persons, who are more likely to be exposed to risk factors such as tobacco use, air pollution, infections such as tuberculosis, and biomass smoke but less likely to have adequate healthcare access. Management of COPD can be challenging across the Americas, with some barriers being specific to certain countries and others shared across the U.S., Canada, and Latin America. Because most cases of COPD are undiagnosed due to suboptimal access to healthcare and pulmonary function testing, and thus cannot be treated, increased access to spirometry would have a substantial impact on disease management across the Americas. For individuals who are diagnosed, access to medications and other interventions is quite variable across and within nations, even in those with universal healthcare systems, such as Canada and Brazil. This emphasizes the importance of collaborative treatment guidelines, which should be adapted for the healthcare systems and policies of each nation or region, as appropriate. To have a positive impact on COPD management in the Americas, we propose actionable items, including the need for all our respiratory societies to engage key stakeholders (e.g., patient-led organizations, professional societies, and governmental and non-governmental agencies) while advocating for campaigns and policies to ensure clean air for all, eliminate tobacco use and enhance coverage for treatment of nicotine dependence, and improve access to early case-finding, diagnosis and treatment for all patients, including underserved and vulnerable populations.

Prognostic utility of B-type natriuretic peptide and 6-min walk test in patients with acute decompensated heart failure.

BACKGROUND: We aimed to assess the utility of B-type natriuretic peptide (BNP) and 6-min walk test (6 MWT) together as predictors of re-hospitalization and mortality in acute decompensated heart failure (ADHF) patients. METHODS: This prospective, observational, comparative study was conducted at a tertiary care center in India between October 2016 and March 2018. Patients (aged≥18 years) with ADHF and left ventricular systolic dysfunction were included in this study. The study group (N = 100 patients) consisted of patients undergoing a second BNP test along with the 6 MWT at the time of discharge and at 3-months of discharge. The control group (N = 100 patients) consisted of patients who did not undergo these tests at discharge and/or at 3-months of discharge. Study endpoints were re-hospitalization within 6-months, and in-patient and 6-month mortality. RESULTS: Total 200 patients diagnosed with ADHF were enrolled. Mean age was 53.46 ± 10.12 years in the study group and 52.98 ± 9.88 years in the control group. ROC analysis of BNP level to predict re-hospitalization revealed AUC of 0.935 (p < 0.001) at admission, 0.915 (p < 0.001) at discharge, and 0.783 (p < 0.001) at 3-months. Similarly, at discharge, ROC analysis of 6 MWT to predict death gave AUC of 0.670 (p = 0.011), and at 3-months, it was 0.838 (p < 0.001). ROC analysis of BNP level to predict mortality showed AUC of 0.960 (p < 0.001) at admission, 0.947 (p < 0.001) after discharge, and 0.960 (p = 0.002) at 3-months. CONCLUSION: BNP levels and 6 MWT have good prognostic utility in ADHF patients, and thus may be beneficial in making therapeutic adjustments and taking precautionary measures in these patients.

Real-world biologics response and super-response in the International Severe Asthma Registry cohort.

BACKGROUND: Biologic asthma therapies reduce exacerbations and long-term oral corticosteroids (LTOCS) use in randomized controlled trials (RCTs); however, there are limited data on outcomes among patients ineligible for RCTs. Hence, we investigated responsiveness to biologics in a real-world population of adults with severe asthma. METHODS: Adults in the International Severe Asthma Registry (ISAR) with ≥24 weeks of follow-up were grouped into those who did, or did not, initiate biologics (anti-IgE, anti-IL5/IL5R, anti-IL4/13). Treatment responses were examined across four domains: forced expiratory volume in 1 second (FEV1) increase by ≥100 mL, improved asthma control, annualized exacerbation rate (AER) reduction ≥50%, and any LTOCS dose reduction. Super-response criteria were: FEV1 increase by ≥500 mL, new well-controlled asthma, no exacerbations, and LTOCS cessation or tapering to ≤5 mg/day. RESULTS: 5.3% of ISAR patients met basic RCT inclusion criteria; 2116/8451 started biologics. Biologic initiators had worse baseline impairment than non-initiators, despite having similar biomarker levels. Half or more of initiators had treatment responses: 59% AER reduction, 54% FEV1 increase, 49% improved control, 49% reduced LTOCS, of which 32%, 19%, 30%, and 39%, respectively, were super-responses. Responses/super-responses were more frequent in biologic initiators than in non-initiators; nevertheless, ~40-50% of initiators did not meet response criteria. CONCLUSIONS: Most patients with severe asthma are ineligible for RCTs of biologic therapies. Biologics are initiated in patients who have worse baseline impairments than non-initiators despite similar biomarker levels. Although biologic initiators exhibited clinical responses and super-responses in all outcome domains, 40-50% did not meet the response criteria.

COVID-19 Pandemic on COPD Healthcare Utilization, Exacerbations and Mortality: A Population Study.

RATIONALE: Existing work suggests that patients with COPD (pwCOPD) presented less frequently to the emergency department (ED) and were less likely to be hospitalized during the COVID-19 pandemic but it is unclear if this was due to improved health and disease management or to increased barriers/avoidance of healthcare. The objective of this study is to determine the impact of the pandemic on inpatient and outpatient healthcare utilization, disease incidence, and mortality rates in pwCOPD. METHODS: A retrospective population-based analysis using linked administrative datasets from Alberta, Canada18 months before and after March 12, 2020 was conducted to measure hospitalization, ED and outpatient visits, and COPD outpatient exacerbations during these time periods. Mortality data was also analyzed pre- versus post-pandemic, taking confirmed COVID-19 infection within 30 days into account. Subgroup analysis based on COPD exacerbation risk stratification was undertaken to determine if healthcare utilization differed based on exacerbation risk. Finally, sex-based analysis of healthcare utilization during the pandemic was also completed. RESULTS: Hospitalization/ED visits and outpatient treatment for acute exacerbations of COPD dropped while total outpatient COPD visits, including both virtual and in-person, increased during the pandemic for pwCOPD. Mortality rate increased even after adjusting for COVID-19-associated deaths. Sex-based subgroup analysis showed a greater drop in acute care utilization for females but the rise in mortality was seen for both sexes with men experiencing greater rate of mortality than women. CONCLUSIONS: Overall pwCOPD accessed acute care resources less during the pandemic which may have contributed to a rise in non-COVID all-cause mortality.

Early Diagnosis and Treatment of COPD and Asthma - A Randomized, Controlled Trial.

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 (FEV1). 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 FEV1 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.).

Association Between T2-related Comorbidities and Effectiveness of Biologics in Severe Asthma.

Rationale: Previous studies investigating the impact of comorbidities on the effectiveness of biologic agents have been relatively small and of short duration and have not compared classes of biologic agents. Objectives: To determine the association between type 2-related comorbidities and biologic agent effectiveness in adults with severe asthma (SA). Methods: This cohort study used International Severe Asthma Registry data from 21 countries (2017-2022) to quantify changes in four outcomes before and after biologic therapy-annual asthma exacerbation rate, FEV1% predicted, asthma control, and long-term oral corticosteroid daily dose-in patients with or without allergic rhinitis, chronic rhinosinusitis (CRS) with or without nasal polyps (NPs), NPs, or eczema/atopic dermatitis. Measurements and Main Results: Of 1,765 patients, 1,257, 421, and 87 initiated anti-IL-5/5 receptor, anti-IgE, and anti-IL-4/13 therapies, respectively. In general, pre- versus post-biologic therapy improvements were noted in all four asthma outcomes assessed, irrespective of comorbidity status. However, patients with comorbid CRS with or without NPs experienced 23% fewer exacerbations per year (95% CI, 10-35%; P < 0.001) and had 59% higher odds of better post-biologic therapy asthma control (95% CI, 26-102%; P < 0.001) than those without CRS with or without NPs. Similar estimates were noted for those with comorbid NPs: 22% fewer exacerbations and 56% higher odds of better post-biologic therapy control. Patients with SA and CRS with or without NPs had an additional FEV1% predicted improvement of 3.2% (95% CI, 1.0-5.3; P = 0.004), a trend that was also noted in those with comorbid NPs. The presence of allergic rhinitis or atopic dermatitis was not associated with post-biologic therapy effect for any outcome assessed. Conclusions: These findings highlight the importance of systematic comorbidity evaluation. The presence of CRS with or without NPs or NPs alone may be considered a predictor of the effectiveness of biologic agents in patients with SA.

Analysis of comorbidities and multimorbidity in adult patients in the International Severe Asthma Registry.

BACKGROUND: Investigation for the presence of asthma comorbidities is recommended by the Global Initiative for Asthma because their presence can complicate asthma management. OBJECTIVE: To understand the prevalence and pattern of comorbidities and multimorbidity in adults with severe asthma and their association with asthma-related outcomes. METHODS: This was a cross-sectional study using data from the International Severe Asthma Registry from 22 countries. A total of 30 comorbidities were identified and categorized a priori as any of the following: (1) potentially type 2-related comorbidities, (2) potentially oral corticosteroid (OCS)-related comorbidities, or (3) comorbidities mimicking or aggravating asthma. The association between comorbidities and asthma-related outcomes was investigated using multivariable models adjusted for country, age at enrollment, and sex (ie male or female). RESULTS: Of the 11,821 patients, 69%, 67%, and 55% had at least 1 potentially type 2-related, potentially OCS-related, or mimicking or aggravating comorbidities, respectively; 57% had 3 or more comorbidities, and 33% had comorbidities in all 3 categories. Patients with allergic rhinitis, nasal polyposis, and chronic rhinosinusitis experienced 1.12 (P = .003), 1.16 (P < .001), and 1.29 times (P < .001) more exacerbations per year, respectively, than those without. Patients with nasal polyposis and chronic rhinosinusitis were 40% and 46% more likely (P < .001), respectively, to have received long-term (LT) OCS. All assessed potential OCS-related comorbidities (except obesity) were associated with a greater likelihood of LTOCS use (odds ratios [ORs]: 1.23-2.77) and, except for dyslipidemia, with a greater likelihood of uncontrolled asthma (ORs: 1.29-1.68). All mimicking or aggravating comorbidities assessed were associated with more exacerbations (1.24-1.68 times more), all (except bronchiectasis) with increased likelihood of uncontrolled asthma (ORs: 1.57-1.81), and all (except chronic obstructive pulmonary disease) with increased likelihood of LTOCS use (ORs: 1.37-1.57). A greater number of comorbidities was associated with worse outcomes. CONCLUSION: In a global study, comorbidity or multimorbidity is reported in most adults with severe asthma and is associated with poorer asthma-related outcomes. CLINICAL TRIAL REGISTRATION: The International Severe Asthma Registry database has ethical approval from the Anonymous Data Ethics Protocols and Transparency (ADEPT) committee (ADEPT0218) and is registered with the European Union Electronic Register of Post-Authorization Studies (European Network Centres for Pharmacoepidemiology and Pharmacovigilance [ENCEPP]/DSPP/23720). The study was designed, implemented, and reported in compliance with the European Network Centres for Pharmacoepidemiology and Pharmacovigilance (ENCEPP) Code of Conduct (EMA 2014; EUPAS44024) and with all applicable local and international laws and regulations, and registered with ENCEPP (https://www.encepp.eu/encepp/viewResource.htm?id=48848). Governance was provided by ADEPT (registration number: ADEPT1121).

Asthma-related emergency admissions and associated healthcare resource use in Alberta, Canada.

BACKGROUND: There is a lack of real-world research assessing asthma management following asthma-related emergency department (ED) discharges. The objective of this study was to characterise follow-up care, healthcare resource use (HCRU) and medical costs following ED admissions in Alberta, Canada. METHODS: A retrospective cohort study was conducted on adults with asthma using longitudinal population-based administrative data from Alberta Health Services. Adult patients with asthma and ≥1 ED admission from 1 April 2015 to 31 March 2020 were included. ED admissions, outpatient visits, hospitalisations and asthma-specific medication use were measured in the 30 days before and up to 90 days after each asthma-related ED admission. Mean medical costs attributable to each type of HCRU were summarised. All outcomes were stratified by patient baseline disease severity. RESULTS: Among 128 063 patients incurring a total of 20 142 asthma-related ED visits, a substantial rate of ED readmission was observed, with 10% resulting in readmissions within 7 days and 35% within 90 days. Rates increased with baseline asthma severity. Despite recommendations for patients to be followed up with an outpatient visit within 2-7 days of ED discharge, only 6% were followed up within 7 days. The mean total medical cost per patient was $C8143 in the 30 days prior to and $C5407 in the 30 days after an ED admission. CONCLUSIONS: Despite recommendations regarding follow-up care for patients after asthma-related ED admissions, there are still low rates of outpatient follow-up visits and high ED readmission rates. New or improved multidimensional approaches must be integrated into follow-up care to optimise asthma control and prevent readmissions.

Estimating the Health and Economic Impact of Improved Management in Prevalent Chronic Obstructive Pulmonary Disease Populations in England, Germany, Canada, and Japan: A Modelling Study.

Introduction: COPD is a leading cause of morbidity and mortality globally. Management is complex and costly. Although international quality standards for diagnosis and management exist, opportunities remain to improve outcomes, especially in reducing avoidable hospitalisations. Objective: To estimate the potential health and economic impact of improved adherence to guideline-recommended care for prevalent, on-treatment COPD populations in four high-income settings. Methods: A disease simulation model was developed to evaluate the impact of theoretical improvements to COPD management, comparing outcomes for usual care and policy scenarios for interventions that reduce avoidable hospitalisations: 1) increased attendance (50% vs 31-38%) of early follow-up review after severe exacerbation hospitalisation; 2) increased access (30% vs 5-10%) to an integrated disease management (IDM) programme that provides guideline adherent care. Results: For cohorts of 100,000 patients, Policy 1 yielded additional life years (England: 523; Germany: 759; Canada: 1316; Japan: 512) and lifetime cost savings (-£2.89 million; -€6.58 million; -$40.08 million; -¥735.58 million). For Policy 2, additional life years (2299; 3619; 3656) and higher lifetime total costs (£38.15 million; €35.58 million; ¥1091.53 million) were estimated in England, Germany and Japan, and additional life years (4299) and cost savings (-$20.52 million) in Canada. Scenarios found that the cost impact depended on the modelled intervention effect size. Conclusion: Interventions that reduce avoidable hospitalisations are estimated to improve survival and may generate cost savings. This study provides evidence on the theoretical impact of policies to improve COPD care and highlights priority areas for further research to support evidence-based policy decisions.

Impact of Undiagnosed Chronic Obstructive Pulmonary Disease and Asthma on Symptoms, Quality of Life, Healthcare Use, and Work Productivity.

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.

2023 Canadian Thoracic Society Guideline on Pharmacotherapy in Patients With Stable COPD.

Chronic obstructive pulmonary disease patient care must include confirming a diagnosis with postbronchodilator spirometry. Because of the clinical heterogeneity and the reality that airflow obstruction assessed by spirometry only partially reflects disease severity, a thorough clinical evaluation of the patient should include assessment of symptom burden and risk of exacerbations that permits the implementation of evidence-informed pharmacologic and nonpharmacologic interventions. This guideline provides recommendations from a comprehensive systematic review with a meta-analysis and expert-informed clinical remarks to optimize maintenance pharmacologic therapy for individuals with stable COPD, and a revised and practical treatment pathway based on new evidence since the 2019 update of the Canadian Thoracic Society (CTS) Guideline. The key clinical questions were developed using the Patients/Population (P), Intervention(s) (I), Comparison/Comparator (C), and Outcome (O) model for three questions that focuses on the outcomes of symptoms (dyspnea)/health status, acute exacerbations, and mortality. The evidence from this systematic review and meta-analysis leads to the recommendation that all symptomatic patients with spirometry-confirmed COPD should receive long-acting bronchodilator maintenance therapy. Those with moderate to severe dyspnea (modified Medical Research Council ≥ 2) and/or impaired health status (COPD Assessment Test ≥ 10) and a low risk of exacerbations should receive combination therapy with a long-acting muscarinic antagonist/long-acting ẞ2-agonist (LAMA/LABA). For those with a moderate/severe dyspnea and/or impaired health status and a high risk of exacerbations should be prescribed triple combination therapy (LAMA/LABA/inhaled corticosteroids) azithromycin, roflumilast or N-acetylcysteine is recommended for specific populations; a recommendation against the use of theophylline, maintenance systemic oral corticosteroids such as prednisone and inhaled corticosteroid monotherapy is made for all COPD patients.

Implementing an Evidence-Based COPD Hospital Discharge Protocol: A Narrative Review and Expert Recommendations.

Discharge bundles, comprising evidence-based practices to be implemented prior to discharge, aim to optimise patient outcomes. They have been recommended to address high readmission rates in patients who have been hospitalised for an exacerbation of chronic obstructive pulmonary disease (COPD). Hospital readmission is associated with increased morbidity and healthcare resource utilisation, contributing substantially to the economic burden of COPD. Previous studies suggest that COPD discharge bundles may result in fewer hospital readmissions, lower risk of mortality and improvement of patient quality of life. However, evidence for their effectiveness is inconsistent, likely owing to variable content and implementation of these bundles. To ensure consistent provision of high-quality care for patients hospitalised with an exacerbation of COPD and reduce readmission rates following discharge, we propose a comprehensive discharge protocol, and provide evidence highlighting the importance of each element of the protocol. We then review care bundles used in COPD and other disease areas to understand how they affect patient outcomes, the barriers to implementing these bundles and what strategies have been used in other disease areas to overcome these barriers. We identified four evidence-based care bundle items for review prior to a patient's discharge from hospital, including (1) smoking cessation and assessment of environmental exposures, (2) treatment optimisation, (3) pulmonary rehabilitation, and (4) continuity of care. Resource constraints, lack of staff engagement and knowledge, and complexity of the COPD population were some of the key barriers inhibiting effective bundle implementation. These barriers can be addressed by applying learnings on successful bundle implementation from other disease areas, such as healthcare practitioner education and audit and feedback. By utilising the relevant implementation strategies, discharge bundles can be more (cost-)effectively delivered to improve patient outcomes, reduce readmission rates and ensure continuity of care for patients who have been discharged from hospital following a COPD exacerbation.

Impact of airway challenges on cardiovascular risk in asthma - a randomized controlled trial.

BACKGROUND: People experiencing asthma exacerbations are at increased risk of cardiovascular events. To better understand the relationship between asthma exacerbations and cardiovascular risk, this randomized case-control, cross-over controlled trial assessed the immediate systemic inflammatory and vascular responses to acutely induced pulmonary inflammation and bronchoconstriction in people with asthma and controls. METHODS: Twenty-six people with asthma and 25 controls underwent three airway challenges (placebo, mannitol, and methacholine) in random order. Markers of cardiovascular risk, including serum C-reactive protein, interleukin-6, and tumor necrosis factor, endothelial function (flow-mediated dilation), microvascular function (blood-flow following reactive hyperemia), and arterial stiffness (pulse wave velocity) were evaluated at baseline and within one hour following each challenge. The systemic responses in a) asthma/control and b) positive airway challenges were analyzed. (ClinicalTrials.gov reg# NCT02630511). RESULTS: Both the mannitol and methacholine challenges resulted in clinically significant reductions in forced expiratory volume in 1 second (FEV1) in asthma (-7.6% and -17.9%, respectively). Following positive challenges, reduction in FEV1 was -27.6% for methacholine and -14.2% for mannitol. No meaningful differences in predictors of cardiovascular risk were observed between airway challenges regardless of bronchoconstrictor response. CONCLUSION: Neither acutely induced bronchoconstriction nor pulmonary inflammation and bronchoconstriction resulted in meaningful changes in systemic inflammatory or vascular function. These findings question whether the increased cardiovascular risk associated with asthma exacerbations is secondary to acute bronchoconstriction or inflammation, and suggest that other factors need to be further evaluated such as the cardiovascular impacts of short-acting inhaled beta-agonists.

Examining changes in vascular function, arterial stiffness and systemic inflammation during hospitalization and recovery from an acute exacerbation of chronic obstructive pulmonary disease.

An acute exacerbation of COPD (AECOPD) is associated with increased risk of cardiovascular (CV) events. The elevated risk during an AECOPD may be related to changes in vascular function, arterial stiffness, and systemic inflammation; the time course of these measures and their corresponding recovery are poorly understood. Further, physical activity is reduced during an AECOPD, and physical activity may influence the cardiovascular responses to an AECOPD. The purpose of the study was to examine the acute impact of an AECOPD requiring hospitalization on vascular function, arterial stiffness, and systemic inflammation and examine whether physical activity modulates these variables during recovery. Patients hospitalized for an AECOPD were prospectively recruited and compared to control patients with stable COPD. Vascular function, arterial stiffness, and systemic inflammation (CRP, IL-6) were measured at hospital admission, hospital discharge and within 14 days of discharge. Physical activity was electronically tracked daily while in hospital and for 7 days following discharge using a Fitbit. One hundred and twenty-one patients with an AECOPD requiring hospitalization and 33 control patients with stable COPD were enrolled in the study. Vascular function was significantly lower, and systemic inflammation higher at hospital admission in patients with an AECOPD compared to stable COPD. Significant improvements in vascular function and inflammation were observed within 14 days of hospital discharge; however, vascular function remained lower than stable COPD. Physical activity was low at admission and increased following discharge; however, physical activity was unrelated to measures of vascular function or inflammation at any time point. An AECOPD requiring hospitalization is associated with impaired vascular function that persists during recovery. These findings provide a mechanistic link to help explain the enduring increase in CV risk and mortality following a severe AECOPD event.Clinical trial registration: ClinicalTrials.gov #NCT01949727; Registered: 09/20/2013.

Pharmacists' chronic disease management in chronic obstructive pulmonary disease: Effect on health services utilization.

BACKGROUND: There is limited real-world evidence on evaluation of chronic disease management initiatives provided by pharmacists to patients with chronic obstructive pulmonary disease (COPD). OBJECTIVE: To evaluate changes in COPD-related health care resource utilization between patients with COPD who had pharmacist-provided chronic disease management (comprehensive annual care plan [CACP]) vs those who did not have CACP. METHODS: Patients with COPD who received a CACP in Alberta between 2012 and 2015 were identified within the Alberta Health administrative data. Each of these patients were matched with 2 control patients with COPD based on age, sex, provider, date of service, and qualifying comorbidities. Controlled interrupted time series analysis was used to evaluate changes in COPD-specific hospitalizations, emergency department (ED) visits, physician visits, and claims for pulmonary function test. Immediate and temporal changes were calculated for the difference in outcomes 1 year before and 1 year after receiving the CACP for the intervention group and matched controls. RESULTS: Eligible patients (N = 74,365), of whom 28,795 (38.7%) had received CACPs, were matched to a total of 45,570 controls. In 1 year after the CACPs implementation, the number of COPD-related hospitalization visits decreased by 174 (95% CI = -270.8 to -76.5) per 10,000 patients per month, COPD-related ED visits decreased by 123 (95% CI = -294.9 to 49.6) per 10,000 per month, general practitioner visits decreased by 153.9 per 10,000 per month (95% CI = -293.3 to -14.5), and pulmonary function test claims decreased by 19.5 per 10,000 per month (95% CI = -70.1 to 31.2) when compared with the matched controls. However, significant difference between the 2 groups was found for COPD-related hospitalizations only, which was not confirmed by the sensitivity analysis. CONCLUSIONS: In patients with COPD who were provided with care plans by their community pharmacists, there was no significant decrease in COPD-related hospitalizations or ED visits over 1 year compared with the matched controls who did not have a pharmacist-provided care plan. Physician visits and pulmonary function tests did not change significantly for those who had CACP compared with those who did not. There is a need to further understand how care plans can better impact other outcomes that are important in COPD management. DISCLOSURES: This study was supported by a grant from the M.S.I. Foundation (Grant#895) based in Alberta, Canada. Dr Bhutani has consulted for Astra Zeneca, GlaxoSmithKline, Boehringer Ingelheim, Valeo, Covis, and Sanofi. The authors declare no other relevant conflicts of interest or financial relationships. This study is based on data provided by Alberta Health. The interpretation and conclusions of the results are those of the researchers and do not necessarily represent the views of the government of Alberta nor the funder (M.S.I. Foundation). All authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors.

Impact of Initiating Biologics in Patients With Severe Asthma on Long-Term Oral Corticosteroids or Frequent Rescue Steroids (GLITTER): Data From the International Severe Asthma Registry.

BACKGROUND: Effectiveness of biologics has neither been established in patients with high oral corticosteroid exposure (HOCS) nor been compared with effectiveness of continuing with HOCS alone. OBJECTIVE: To examine the effectiveness of initiating biologics in a large, real-world cohort of adult patients with severe asthma and HOCS. METHODS: This was a propensity score-matched, prospective cohort study using data from the International Severe Asthma Registry. Between January 2015 and February 2021, patients with severe asthma and HOCS (long-term OCSs for ≥1 year or ≥4 courses of rescue OCSs within a 12-month period) were identified. Biologic initiators were identified and, using propensity scores, matched 1:1 with noninitiators. The impact of biologic initiation on asthma outcomes was assessed using generalized linear models. RESULTS: We identified 996 matched pairs of patients. Both groups improved over the 12-month follow-up period, but improvement was greater for biologic initiators. Biologic initiation was associated with a 72.9% reduction in the average number of exacerbations per year versus noninitiators (0.64 vs 2.06; rate ratio, 0.27 [95% CI, 0.10-0.71]). Biologic initiators were 2.2 times more likely than noninitiators to take a daily long-term OCS dose of less than 5 mg (risk probability, 49.6% vs 22.5%; P = .002) and had a lower risk of asthma-related emergency department visits (relative risk, 0.35 [95% CI, 0.21-0.58]; rate ratio, 0.26 [0.14-0.48]) and hospitalizations (relative risk, 0.31 [95% CI, 0.18-0.52]; rate ratio, 0.25 [0.13-0.48]). CONCLUSIONS: In a real-world setting, including patients with severe asthma and HOCS from 19 countries, and within an environment of clinical improvement, initiation of biologics was associated with further improvements across multiple asthma outcomes, including exacerbation rate, OCS exposure, and health care resource utilization.

Mental health of health care workers during the hour of crisis - A study from tertiary care hospital in North India.

Background and Aims: This cross-sectional study aimed to analyze the psychosocial, behavioral, and sleep impact of coronavirus disease-19 (COVID-19) pandemic on healthcare workers (HCWs) at a tertiary-care hospital in Northern India. Materials and Methods: An online questionnaire including three psychological scales - peritraumatic distress inventory (PDI), insomnia Severity Index (ISI), and Depression anxiety stress scale was circulated among the HCWs at a tertiary-care hospital in Northern India. Results: Three hundred and ninety-six HCWs (Mean age standard deviation: 34.8 [8.1%] years; 181 females) responded. Place of posting was active COVID area (27.2%), reserve active COVID team (23.2%), trained reserve pool (29.5%), and non-COVID areas (19.9%). More than half of all the respondents (51%) had abnormal PDI score (>14) with a propensity to develop posttraumatic stress disorder. Furthermore, there was a significantly higher prevalence of abnormal PDI scores in those involved in active COVID care units (74%) versus non-COVID care unit (24%, P = 0.001). More than 60% of all the respondents had abnormal ISI score suggesting significant insomnia. Stress was seen in 71% of all the respondents while 82% were anxious and 77% participants had depressive symptoms. Hence, the psychological morbidity among the HCWs was high. Conclusion: Our study found a much higher prevalence of peritraumatic distress, insomnia, anxiety, stress, and depression among the HCWs, more so in those working in COVID areas. Factors indigenous to Indian population in terms of psychological health must be studied and addressed to reduce this psychological morbidity since the battle with COVID is long.