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

The objective of this study was to identify the necessary features of pulmonary telerehabilitation (P-TR) from the perspectives of individuals living with chronic lung disease and health care professionals (HCPs) who deliver pulmonary rehabilitation (PR). Focus groups were carried out with patients (n = 26) and HCPs (n = 26) to elicit and explore their opinions about the critical elements of in-person PR and ideas for how these elements could be supported using technology. A questionnaire was used to assess technology use, PR experience, and general health status. Four key elements of PR were identified as critical to P-TR: the social aspect of PR; communicating with HCPs for education and support; using biosensors for monitoring and promoting self-knowledge; and the evolution of support with progress over time. A range of technology-enabled devices and programs were suggested as means to recreate aspects of these integral elements. Consultations with patients and HCPs suggest that users are interested in technology and want to ensure it recreates the important aspects of PR. Patients and HCPs identified similar key elements for P-TR. The opinions and suggestions of patients and HCPs should be the driving force of innovation if P-TR is to succeed in improving health outcomes. [ABSTRACT FROM AUTHOR]

Background Recently, several proteins of the extracellular matrix have been characterised as active contributors to allergic airway disease. Microfibrillarassociated protein 4 (MFAP4) is an extracellular matrix protein abundant in the lung, whose biological functions remain poorly understood. In the current study we investigated the role of MFAP4 in experimental allergic asthma. Methods MFAP4-deficient mice were subjected to alum/ovalbumin and house dust mite induced models of allergic airway disease. In addition, human healthy and asthmatic primary bronchial smooth muscle cell cultures were used to evaluate MFAP4-dependent airway smooth muscle responses. Results MFAP4 deficiency attenuated classical hallmarks of asthma, such as eosinophilic inflammation, eotaxin production, airway remodelling and hyperresponsiveness. In wild-type mice, serum MFAP4 was increased after disease development and correlated with local eotaxin levels. MFAP4 was expressed in human bronchial smooth muscle cells and its expression was upregulated in asthmatic cells. Regarding the underlying mechanism, we showed that MFAP4 interacted with integrin αvβ5 and promoted asthmatic bronchial smooth muscle cell proliferation and CCL11 release dependent on phosphatidyloinositol-3-kinase but not extracellular signal-regulated kinase pathway. Conclusions MFAP4 promoted the development of asthmatic airway disease in vivo and pro-asthmatic functions of bronchial smooth muscle cells in vitro. Collectively, our results identify MFAP4 as a novel contributor to experimental asthma, acting through modulation of airway smooth muscle cells. [ABSTRACT FROM AUTHOR]

INTRODUCTION/OBJECTIVE: Individuals using home mechanical ventilation (HMV) frequently choose to live at home for quality of life, despite financial burden. Previous studies of healthcare utilization and costs do not consider public and private expenditures, including care-giver time. This study determined public and private healthcare utilization and costs for HMV users living at home in two Canadian provinces, and examined factors associated with higher costs. METHODOLOGY: Longitudinal, prospective observational study (April 2012 to August 2015) collecting data on public and private (out-of-pocket, third party insurance, caregiving) costs every 2 weeks for 6 months using the Ambulatory Home Care Record. Functional Independence Measure (FIM) was used at baseline and study completion. Regression models examined variables associated with total monthly costs. A priori variables selected using Andersen and Newman's framework for healthcare utilization, relevant literature, and clinical expertise. Data in 2015 Canadian dollars. RESULTS: We enrolled 134 HMV users; 95 with family caregivers. Overall median (interquartile range) monthly healthcare cost was $5275 ($2291-$10,181) with $2410 (58%) publicly funded; $1609 (39%) family caregiving; and $141 (3%) out-of-pocket (<1% third party insurance). Median healthcare costs were $8733 ($5868-$ 15,274) for those inva-sively ventilated and $3925 ($1212-$7390) for non-invasive ventilation. Variables associated with highest monthly costs were Amyotrophic Lateral Sclerosis (1.88, 95% CI 1.09-3.26, p < 0.03) and lower FIM quintiles (higher dependency) (up to 6.98, 95% CI 3.88-12.55, p < 0.0001) adjusting for age, sex, tracheostomy, and ventilation duration. CONCLUSIONS: For individuals using HMV and living at home, most healthcare costs were publicly supported or associated with family care-giving. Highest costs were incurred by the most dependent users. Understanding healthcare costs for community-residing HMV users will inform policy decisions to optimize resource allocation, helping these individuals live at home while minimizing caregiver burden. [ABSTRACT FROM AUTHOR]

A biosensor that can detect biomarkers accurately, quickly, and conveniently is important for the diagnosis of various diseases. However, most of the existing detection methods require sample extraction, which makes it difficult to detect and image intracellular molecules or to detect two different types of biomarkers simultaneously. In this study, we constructed a DNA tetrahedral nanoprobe (DTP) capable of detecting both miR378 and telomerase, both of which are tumor markers. In the presence of miR378, FAM on the molecular beacon of DTP fluoresced via Förster resonance energy transfer (FRET), and the limit of detection was 476 pM with excellent specificity. When present, telomerase binds to telomerase substrate (TS) primers, extending the repeat sequence (TTAGGG) n to trigger Cy3 fluorescence. A strong linear relationship existed between the fluorescence intensity of Cy3 and the number of HeLa cells. The limit of detection was 800 HeLa cells. In addition, DTP was less cytotoxic to and biocompatible with HeLa cells and fluoresced only in cancer cells, which can help to sensitively distinguish between normal and cancer cells. In conclusion, DTP can simultaneously detect the content of miR378 and activity of telomerase and realize intracellular imaging, which has broad application prospects in early cancer diagnosis and treatment.

Acute short-term noninvasive ventilation (NIV) for hypercapnic respiratory failure in chronic obstructive pulmonary disease (COPD) has well-established benefits; however, the role of long-term home NIV remains controversial. In the past decade, studies utilizing aggressive NIV settings to maximally reduce carbon dioxide levels (PaCO 2 ) have resulted in several positive clinical trials and led to updated guidelines on home NIV for stable hypercapnic COPD patients. This clinical respiratory review discusses the high-intensity NIV approach, summarizes recent key trials and guidelines pertaining to home NIV in COPD, and considers key clinical questions for future research and application in the Canadian context. With recent evidence and Canadian Thoracic Society (CTS) guidelines supporting the use of NIV in carefully selected COPD patients with persistent daytime hypercapnia, we believe it is time to reconsider our approach., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Rachel Jen et al.)

In India, the levels of pesticide residues in Raw Agricultural Commodities (RAC) are being subjected to adequate legal regulations, and the health-risks associated with them are determined from time to time adhering to global standards. Since RACs are generally consumed by humans as the processed foods (PF), it is imperative to monitor the levels of pesticide residues in them in order to approach a realistic analysis of dietary exposure and concomitant health risk assessment. In India, production and consumption of PFs have a rising trend and hence it is indispensable to monitor the residue levels of pesticides in largely consumed PFs. Depending on the processing methods and physicochemical properties of pesticides, the residue levels may decrease or increase in a PF when compared to the corresponding RAC. While obtaining data on processing factors (Pf), it is pragmatic to focus on those situations in which the residues get concentrated following the processing step. Currently, regulatory agencies of several countries and the CODEX have determined the levels of pesticide residues in processed agriculture commodities, arrived at the Pfs, and fixed the maximum residue levels. Since consumption of PFs in India has tremendously increased in recent times and there is paucity of data about their health risks/benefits, it is imminent to deliberate on the complexities associated with the issues of adopting the Pfs generated by other regulatory agencies and subsequently examine the possibilities of generating the required data on Pfs on a priority basis to enable a comprehensive risk assessment., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© Association of Food Scientists & Technologists (India) 2022.)

Introduction: Retaining participants in longitudinal studies increases their power. We undertook this study in a population-based longitudinal cohort of adults with COPD to determine the factors associated with increased cohort attrition., Methods: In the longitudinal population-based Canadian Cohort of Obstructive Lung Disease (CanCOLD) study, 1561 adults > 40 years old were randomly recruited from 9 urban sites. Participants completed in-person visits at 18-month intervals and also were followed up every 3 months over the phone or by email. The cohort retention for the study and the reasons for attrition were analyzed. Hazard ratios and robust standard errors were calculated using Cox regression methods to explore the associations between participants who remained in the study and those who did not., Results: The median follow-up (years) of the study is 9.0 years. The overall mean retention was 77%. Reasons for attrition (23%) were: dropout by participant (39%), loss of contact (27%), investigator-initiated withdrawal (15%), deaths (9%), serious disease (9%), and relocation (2%). Factors independently associated with attrition were lower educational attainment, higher pack-year tobacco consumption, diagnosed cardiovascular disease, and a higher Hospital Anxiety and Depression Scale score: adjusted hazard ratios (95% confidence interval) were 1.43(1.11, 1.85); 1.01(1.00, 1.01); 1.44(1.13, 1.83); 1.06(1.02, 1.10) respectively., Conclusions: Identification and awareness of risk factors for attrition could direct targeted retention strategies in longitudinal studies. Moreover, the identification of patient characteristics associated with study dropout could address any potential bias introduced by differential dropouts., (JCOPDF © 2023.)

Introduction: Family caregivers play an important role supporting the day-to-day needs of ventilator-assisted individuals (VAIs) living at home. Peer-to-peer communication can help support these caregivers and help them sustain caregiving in the community. Online peer-support has been suggested as a way to help meet caregivers' support needs., Methods: A qualitative descriptive approach was used to elicit the perspectives of support received from caregivers who participated in a pilot web-based peer support program from October to December 2018. Data were collected through the transcripts of weekly online peer-to-peer group chats. Data were analyzed using an integration of thematic and framework analysis., Results: In total, eight caregivers and five peer mentors participated in the pilot. All five mentors and four of the caregivers participated in the weekly chats. We identified three themes, a) The experience of caregivers is characterized by unique challenges related to the complexity of VAI care including technology; b) Mentors and caregiver participants reciprocally share support; c) Despite hardships, there are things that make caregiving easier and joyful., Discussion: Our results add to the growing body of evidence pointing to the importance of online communities for supporting vulnerable caregivers. The reciprocal element of peer support, where trained mentors and untrained participants both benefit from support, can help sustain peer-support interventions. Despite the challenges of providing care to a VAI, there are facilitators that may help ease the caregiving experience and caregivers can benefit from ongoing support that is tailored to their needs along the caregiving trajectory., Competing Interests: The authors have no conflicts of interest to declare. The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Background: Cervical spinal cord injury (SCI) can lead to dependence on mechanical ventilation (MV) with significant morbidity and mortality. The diaphragm pacing system (DPS) was developed as an alternative to MV., Methods: We conducted a prospective single-arm study of DPS in MV-dependent patients with high SCI and intact phrenic nerves. Following device acclimation, pacing effectiveness to provide ventilation was evaluated. The primary endpoint was the number who could use DPS to breathe for 4 continuous hours without MV. Secondary endpoints included the number of patients that could use DPS 24 h/day free of MV and the ability of DPS to maintain clinically acceptable tidal volume (Vt). In addition, we conducted a meta-analysis that included the prospective study along with data from four recently published studies to evaluate DPS hourly use., Results: Fifty-three patients were implanted in the prospective study. Most were male (77.4%) with a median time from injury to treatment of 28.3 (IQR: 12.1, 83.3) months. Four- and 24-h use occurred in 96.2% (95% CI: 87.0%, 99.5%) and 58.5% (95% CI: 44.1%, 74.9%), respectively. Four and 24-h results in the meta-analysis cohort (n = 196) exhibited similar results 92.2% (95% CI: 82.6%, 96.7%) and 52.7% (95% CI: 36.2%, 68.6%) using DPS for 4 and 24 h, respectively. DPS use significantly exceeded the calculated basal tidal volume requirements by a mean of 48.4% (95% CI: 37.0, 59.9%; p < 0.001)., Conclusions: This study demonstrates that in most ventilator-dependent patients, diaphragm pacing can effectively supplement or completely replace the need for MV and support basal metabolic requirements., (© 2022 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Purpose: Effectively controlling the accumulation of adipose tissue can be a therapeutic strategy for treating obesity, which is a global problem. The present study was designed for comparative assessment of in vitro antiobesity activities of the Psoralea corylifolia -dichloromethane seed extract (DCME) and the isolated phytochemicals, bakuchiol, isopsoralen, and psoralen, through antiadipogenesis and pancreatic lipase (PL) inhibition assays. Material and Methods. In vitro pancreatic lipase activity was determined spectrophotometrically by measuring the hydrolysis of p -nitrophenyl butyrate ( p -NPB) to p -nitrophenol at 405 nm, and adipogenesis was assayed in 3 T3-L1 adipocytes (by using Oil Red O staining) using P. corylifolia -dichloromethane seed extract (DCME) and individual compounds, isolated from the extract., Result: Antilipase as well as antiadipogenesis activity was displayed by both the DCME and the compounds. Maximum antilipase property was recorded in DCME (26.02 ± .041%) at 100  μ g/ml, while, among the isolated compounds, bakuchiol exhibited a higher activity (24.2 ± 0.037%) at 100  μ g/ml concentration, compared to other isolates. DCME was found to exhibit antiadipogenesis property, 75 ± 0.003% lipid accumulation, compared to the control at 100  μ g/ml dose. Bakuchiol, isopsoralen, and psoralen inhibited the lipid accumulation in 3T3-L1 preadipocytes, 78.06 ± 0.002%, 80.91 ± 0.004%, and 80.91 ± 0.001%, respectively, lipid accumulation in comparison to control at 25  μ M dose., Conclusion: The present study highlights the antiobesity potential of P. corylifolia and its active constituents. Thus, it can be concluded that P. corylifolia has the potential to treat obesity and related diseases; however, further research on dose standardization and clinical trials are required., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2022 Neha Mahajan et al.)

Most pulmonary rehabilitation (PR) programs have had to adapt due to the COVID-19 pandemic and associated restrictions. Current alternative home-based programs have limitations and require modification. In this paper, we outline a novel method to monitor home-based PR programs, which has the potential to improve PR safety and efficacy. This new method is based on a remote patient monitoring (RPM) system with connected smart devices that enables the Respiratory Therapist (RT) to have real-time access to patient data including heart rate and peripheral oxygen saturation during exercise. The RPM system also monitors daily physical activity, sedentary time, sleep quality, rescue inhaler use, and maintenance inhaler adherence, among other variables, which has the added advantage of predicting patterns consistent with symptoms that may require medical intervention. To increase privacy, data are anonymized at all levels and only the RT has access to patient information. RPM systems have the potential to give practitioners a holistic view of the participants' health status to better evaluate them during the entire PR program and to improve self-management. As this is not a formal research study, we cannot make definitive conclusions about the efficacy of the system, and further research is needed to examine safety and to compare our approach to other ways of conducting PR.

Histologic and bacteriologic features for groups of average 31-day-old broilers displaying three gross categories of femoral head alterations were documented. Categories included simple femoral head separation (FHS), femoral head transitional changes (FHT), and femoral head necrosis (FHN). Groups with grossly normal (NORM) femoral heads and cull birds with FHN and having gross signs of sepsis (Cull-FHN) were also included in the study. There was a 10% occurrence of positive bacterial cultures for all birds tested. Most positive cultures (33%) were found in the Cull-FHN group, while only a 12% occurrence was seen in the FHS group, and no positives were present in the FHT or FHN groups. A 14% total occurrence of femoral bacterial chondronecrosis with osteomyelitis or simple osteomyelitis (BCO-O) was observed. A progressive increase in the prevalence of BCO-O was apparent between groups going from NORM (0%), FHS (4%), FHT (14%), FHN (13%), and reaching a maximum of 67% in the Cull-FHN group. Minimal to mild femoral head cartilage necrosis was present in 40% of NORM broilers and 100% of the FHS, FHT, and FHN groups, but at moderate severity in 20% of the Cull-FHN group. Thus, the majority of FHN cases were associated with aseptic cartilage necrosis rather than BCO-O. These findings suggest that aseptic cartilage necrosis may be as important as septic necrosis as a cause of gross femoral head disease. A 26% overall occurrence was seen for hip synovitis-arthritis, but group differences were not statistically significant. Synovitis was not seen in the NORM group and was present in some (12%) of the FHS group but was observed at a high rate in both the FHN (43%) and the Cull-FHN (50%) groups. Morphometric measurements demonstrated that the area size of femoral fibrous cortical defects or "cutback zones" were generally larger for all gross categories relative to NORM, with a significant difference between NORM and FHS groups. This study underscores the multifactorial etiology of FHN and the importance of conducting both histologic and bacteriologic evaluations in which gross evidence of FHN or BCO-O occurs.

The purpose of this study was to examine scalene (SA) and sternocleidomastoid (SM) activation during normoxic (norm-ITL; FIO 2  = 21%) and hypoxic (hyp-ITL; FIO 2  = 15%) incremental inspiratory threshold loading (ITL). Thirteen healthy participants (33 ± 4 years, 9 female) performed two ITL tests breathing randomly assigned gas mixtures through an inspiratory loading device where the load was increased every two minutes until task failure. SA and SM root mean square (RMS) electromyography (EMG) were calculated and expressed as a percentage of maximum (RMS %max ) to reflect muscle activation intensity. Myoelectric manifestations of fatigue were characterized as decreased SA or SM EMG median frequency during maximum inspiratory pressure maneuvers before and after ITL. Dyspnea was recorded at baseline and task failure. Ventilatory parameters and mouth pressure (Pm) were recorded throughout the ITL. SA,RMS %max and SM,RMS %max increased in association with ITL load (p ≤ .01 for both). SA,RMS %max was similar between norm-ITL and hyp-ITL (p = .17), whereas SM,RMS %max was greater during the latter (p = .001). Neither SA nor SM had a decrease in EMG median frequency after ITL (p = .75 and 0.69 respectively). Pm increased in association with ITL load (p < .001) and tended to be higher during hyp-ITL compared to norm-ITL (p = .05). Dyspnea was similar during both conditions (p > .05). There was a trend for higher tidal volumes during hyp-ITL compared to norm-ITL (p = .10). Minute ventilation was similar between both conditions (p = .23). RMS, %max of the SA and SM increased linearly with increasing ITL. The presence of hypoxia only increased SM activation. Neither SA nor SM presented myoelectric manifestations of fatigue during both conditions., (© 2020 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Background: Previous studies have associated marijuana exposure with increased respiratory symptoms and chronic bronchitis among long-term cannabis smokers. The long-term effects of smoked marijuana on lung function remain unclear., Methods: We determined the association of marijuana smoking with the risk of spirometrically defined chronic obstructive pulmonary disease (COPD) (post-bronchodilator forced expiratory volume in 1 s (FEV 1 )/forced vital capacity ratio <0.7) in 5291 population-based individuals and the rate of decline in FEV 1 in a subset of 1285 males and females, aged ≥40 years, who self-reported use (or non-use) of marijuana and tobacco cigarettes and performed spirometry before and after inhaled bronchodilator on multiple occasions. Analysis for the decline in FEV 1 was performed using random mixed effects regression models adjusted for age, sex and body mass index. Heavy tobacco smoking and marijunana smoking was defined as >20 pack-years and >20 joint-years, respectively., Results: ∼20% of participants had been or were current marijuana smokers with most having smoked tobacco cigarettes in addition (83%). Among heavy marijuana users, the risk of COPD was significantly increased (adjusted OR 2.45, 95% CI 1.55-3.88). Compared to never-smokers of marijuana and tobacco, heavy marijuana smokers and heavy tobacco smokers experienced a faster decline in FEV 1 by 29.5 mL·year -1 (p=0.0007) and 21.1 mL·year -1 (p<0.0001), respectively. Those who smoked both substances experienced a decline of 32.31 mL·year -1 (p<0.0001)., Interpretation: Heavy marijuana smoking increases the risk of COPD and accelerates FEV 1 decline in concomitant tobacco smokers beyond that observed with tobacco alone., Competing Interests: Conflict of interest: W.C. Tan reports grants from Canadian Institute of Heath Research (CIHR/Rx&D Collaborative Research Program Operating Grants-93326) with industry partners AstraZeneca Canada Ltd, Boehringer Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd, Merck, Novartis Pharma Canada Inc., Nycomed Canada Inc., Pfizer Canada Ltd, during the conduct of the study. Conflict of interest: J. Bourbeau reports grants from Canadian Institute of Heath Research (CIHR/Rx&D Collaborative Research Program Operating Grants-93326) with industry partners AstraZeneca Canada Ltd, Boehringer Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd, Merck, Novartis Pharma Canada Inc., Nycomed Canada Inc., Pfizer Canada Ltd, during the conduct of the study. Conflict of interest: S.D. Aaron has nothing to disclose. Conflict of interest: J.C. Hogg has nothing to disclose. Conflict of interest: F. Maltais has nothing to disclose. Conflict of interest: P. Hernandez reports grants from Canadian Institute Health Research, during the conduct of the study; grants and personal fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis and Takeda, personal fees from Merck, Grifols, Pfizer and Almirall, grants from CSL Behring, outside the submitted work. Conflict of interest: D.D. Marciniuk has nothing to disclose. Conflict of interest: K.R. Chapman reports grants from Novartis, Almirall, Boehringer Ingelheim, Forest, GSK, AstraZeneca, Amgen, Roche, CSL Behring, Grifols, Genentech and Kamada, during the conduct of the study; UHN administered personal support from CIHR (GSK Research Chair in Respiratory Health Care Delivery), outside the submitted work. Conflict of interest: T. To has nothing to disclose. Conflict of interest: J.M. FitzGerald has nothing to disclose. Conflict of interest: B.L. Walker reports grants from Canadian Institute of Health Research, AstraZeneca Canada Ltd, Boehringer Ingelheim Canada, GlaxoSmithKline Canada and Novartis, during the conduct of the study; grants from Respiratory Health Strategic Clinical Network Alberta, personal fees from AstraZeneca, GlaxoSmithKline and Novartis, outside the submitted work. Conflict of interest: J. Road has nothing to disclose. Conflict of interest: L. Zheng has nothing to disclose. Conflict of interest: G. Zhou has nothing to disclose. Conflict of interest: T. Yau has nothing to disclose. Conflict of interest: A. Benedetti has nothing to disclose. Conflict of interest: D. O'Donnell has nothing to disclose. Conflict of interest: D.D. Sin reports grants from Merck, personal fees for advisory board work from Sanofi-Aventis and Regeneron, grants and personal fees from Boehringer Ingelheim, grants and personal fees for lectures and advisory board work from AstraZeneca, personal fees for lectures and advisory board work from Novartis, outside the submitted work., (Copyright ©ERS 2019.)

Background: COPD increases susceptibility to sleep disturbances, which may in turn predispose to increased respiratory symptoms. The objective of this study was to evaluate, in a population-based sample, the relationship between subjective sleep quality and risk of COPD exacerbations., Methods: Data were obtained from the Canadian Cohort Obstructive Lung Disease (CanCOLD) study. Participants with COPD who had completed 18 months of follow-up were included. Sleep quality was measured with the Pittsburgh Sleep Quality Index (PSQI) and a three-factor analysis. Symptom-based (dyspnea or sputum change ≥ 48 h) and event-based (symptoms plus medication or unscheduled health services use) exacerbations were assessed. Association of PSQI with exacerbation rate was assessed by using negative binomial regression. Exacerbation-free survival was also assessed., Results: A total of 480 participants with COPD were studied, including 185 with one or more exacerbations during follow-up and 203 with poor baseline sleep quality (PSQI score > 5). Participants with subsequent symptom-based exacerbations had higher median baseline PSQI scores than those without (6.0 [interquartile range, 3.0-8.0] vs 5.0 [interquartile range, 2.0-7.0]; P = .01), and they were more likely to have baseline PSQI scores > 5 (50.3% vs 37.3%; P = .01). Higher PSQI scores were associated with increased symptom-based exacerbation risk (adjusted rate ratio, 1.09; 95% CI, 1.01-1.18; P = .02) and event-based exacerbation risk (adjusted rate ratio, 1.10; 95% CI, 1.00-1.21; P = .048). The association occurred mainly in those with undiagnosed COPD. Strongest associations were with Factor 3 (sleep disturbances and daytime dysfunction). Time to symptom-based exacerbation was shorter in participants with poor sleep quality (adjusted hazard ratio, 1.49; 95% CI, 1.09-2.03)., Conclusions: Higher baseline PSQI scores were associated with increased risk of COPD exacerbation over 18 months' prospective follow-up., (Copyright © 2019. Published by Elsevier Inc.)

Background and Aim: Telehealth is a strategy to expand the reach of pulmonary rehabilitation (PR). Smartphones can monitor and transmit oxygen saturation (SpO 2 ) and heart rate (HR) data to ensure patient safety during home-based or other exercise. The purpose of this study was to evaluate the usability, validity and reliability of a Kenek O 2 pulse oximeter and custom prototype smartphone application (smartphone oximeter) during rest and exercise in healthy participants and those with chronic lung disease., Methods: Fifteen individuals with chronic lung disease and 15 healthy controls were recruited. SpO 2 and HR were evaluated at rest and during cycling and walking. SpO2 was valid if the mean bias was within +±2%, the level of agreement (LoA) was within ±4%; HR was valid if the mean bias was within ±5 beats per min (bpm), LoA was within ±10bpm. Usability was assessed with a questionnaire and direct observation., Results: The smartphone oximeter was deemed easy to use. At rest, SpO 2 measures were valid in both groups (bias <2%, lower bound LoA -2 to 3%). During exercise, SpO 2 measurement did not meet validity and reliability thresholds in the patients with chronic lung disease, but was accurate for the healthy controls. HR recording during exercise or rest was not valid (LoA>10bpm) in either group., Conclusions: The smartphone oximeter did not record HR or SpO 2 accurately in patients with chronic lung disease during exercise, although SpO 2 was valid at rest. During exercise, patients with chronic lung disease should pause to ensure greatest accuracy of SpO 2 and HR measurement., (Copyright © 2018. Published by Elsevier Ltd.)

Background: Across Europe, Canada, Australia, and the United States, the prevalence of home mechanical ventilation (HMV) prevalence is 6.6-12.9 per 100,000. At-home ventilator-assisted individuals (VAIs) are often vulnerable and highly comorbid, requiring complex care. In Canada, most VAI care is provided by family, leading to poor health-related quality of life and increased caregiver burden. No supportive interventions or peer support programs are tailored to VAI caregivers. Owing to the financial, geographic, and time limitations, Web-based support delivery may especially meet VAI family caregiver needs. We have developed a peer mentor training and Web-based peer support program for VAI caregivers including information-sharing, peer-to-peer communication, and peer mentorship., Objective: Study Stage 1 aims to (1) evaluate the face and content validity of the peer mentor training program and (2) investigate participant satisfaction. Study Stage 2 aims to evaluate (1) the feasibility of participant recruitment and Web-based program delivery; (2) acceptability, usability, and satisfactoriness; (3) experiences of caregivers and peer mentors with the Web-based peer support program; and (4) effect of the Web-based peer support program on caregiver health outcomes., Methods: Study Stage 1: We will train 7 caregivers to act as peer mentors for the Web-based peer support program trial; they will complete questionnaires rating the utility of individual training sessions and the training program overall. Study Stage 2: We will recruit 30 caregiver peers for a pilot randomized controlled trial of the 12-week Web-based peer support program using a waitlist control; the program includes private chat, a public discussion forum, and weekly moderated chats. Caregiver peers will be randomized to the intervention or waitlist control group using a 1:1 ratio using Randomize.net. Both groups will complete pre- and postintervention health outcome questionnaires (ie, caregiving impact, mastery, coping, personal gain, positive affect, and depression). Caregiver peers in the intervention arm will only complete a program evaluation and will be invited to participate in an interview to provide insight into their experience. Peer mentors will be invited to participate in a Web-based focus group to provide insight into their experience as mentors. We will judge the feasibility per the number of recruitment and program delivery goals met, use analysis of covariance to compare health outcomes between intervention and control groups, and analyze qualitative data thematically., Results: Peer mentor training was completed with 5 caregivers in July 2018. To date, 2 caregivers have beta-tested the website, and the Web-based peer support program trial will commence in September 2018. Results are expected by early 2019., Conclusions: This study will result in the production and initial evaluation of a rigorously developed, evidence- and stakeholder-informed Web-based peer training and peer support program for caregivers of VAIs residing at home., International Registered Report Identifier (irrid): PRR1-10.2196/11827., (©Marina B Wasilewski, Mika Nonoyama, Craig Dale, Douglas A McKim, Jeremy Road, David Leasa, Roger Goldstein, Louise Rose. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 06.02.2019.)

Two experiments were conducted to evaluate the performance responses of finishing feedlot cattle to dietary addition of essential oils and exogenous enzymes. The treatments in each experiment consisted of (DM basis): MON-sodium monensin (26 mg/kg); BEO-a blend of essential oils (90 mg/kg); BEO+MON-a blend of essential oils plus monensin (90 mg/kg + 26 mg/kg, respectively); BEO+AM-a blend of essential oils plus exogenous α-amylase (90 mg/kg + 560 mg/kg, respectively); and BEO+AM+PRO-a blend of essential oils plus exogenous α-amylase and exogenous protease (90 mg/kg + 560 mg/kg + 840 mg/kg, respectively). Exp. 1 consisted of a 93-d finishing period using 300 Nellore bulls in a randomized complete block design. Animals fed BEO had higher DMI (P < 0.001) but similar feed efficiency to animals fed MON (P ≥ 0.98). Compared with MON, the combination of BEO+AM resulted in 810 g greater DMI (P = 0.001), 190 g greater average daily gain (P = 0.04), 18 kg heavier final body weight (P = 0.04), and 12 kg heavier hot carcass weight (P = 0.02), although feed efficiency was not significantly different between BEO+AM and MON (P = 0.89). Combining BEO+MON tended to decrease hot carcass weight compared with BEO alone (P = 0.08) but not compared with MON (P = 0.98). Treatments did not impact observed dietary net energy values (P ≥ 0.74) or the observed:expected net energy ratio (P ≥ 0.11). In Exp. 2, five ruminally cannulated Nellore steers were used to evaluate intake, apparent total tract digestibility of nutrients, and ruminal parameters in a 5 × 5 Latin square design. Feeding BEO increased the total tract digestibility of CP compared to MON (P = 0.03). Compared to MON, feeding the combination of BEO+MON increased the intake of CP (P = 0.04) and NDF (P = 0.05), with no effects on total tract digestibility of nutrients (P ≥ 0.56), except for a tendency (P = 0.09) to increase CP digestibility. Intakes of all nutrients measured, except for ether extract (P = 0.16) were greater in animals fed BEO+AM when compared with MON (P ≤ 0.03), with no differences on total tract nutrient digestibilities (P ≥ 0.11) between these two treatments. In summary, diets containing the BEO used herein enhanced DMI of growing-finishing feedlot cattle compared with a basal diet containing MON without impair feed efficiency. A synergism between BEO and AM was detected, further increasing cattle performance and carcass production compared to MON.

Background: Regular monitoring combined with early and appropriate use of airway clearance can reduce unplanned hospital admissions for patients with neuromuscular disease (NMD) and spinal cord injury (SCI). We aimed to describe and compare knowledge of guidelines, monitoring of cough effectiveness, clinician prescription/provision of airway clearance strategies, and service provision constraints in the United Kingdom and Canada., Methods: This was a cross-sectional survey of clinicians affiliated with NMD and SCI clinics in Canada, 2016 attendees at the Home Mechanical Ventilation Conference in the United Kingdom, and United Kingdom physiotherapist networks., Results: We received 155 surveys (92 from Canada; 63 from the United Kingdom). More UK respondents (76%) were aware of airway clearance guidelines than Canadian (56%) respondents ( P = .02). Routine assessment of cough effectiveness was reported by more UK respondents (59%) than Canadian (42%) respondents ( P = .044). Cough peak flow (CPF) was the most common method used in both countries, although it was more commonly used in the UK (96%) than in Canada (81%, P = .02). Fewer Canadian respondents reported using CPF before initiation of airway clearance (81% vs 94%, P = .046), and fewer Canadian respondents showed results to patients for technique feedback (76% vs 97%, P = .007). Similar participant numbers reported using CPF after initiation to ensure adequate technique (73% vs 72%, P = .92). Mechanical insufflation-exsufflation (MI-E) + lung volume recruitment (LVR) + manually assisted cough when CPF ≤ 270 L/min was most routinely recommended (41% overall). Monotherapy was infrequent (LVR 15%, manually assisted cough 7%, and MI-E 4%). More Canadians identified constraints on service provision, specifically insufficient public funding for equipment (68% vs 39%, P = .002) and inadequate community workers' knowledge (56% vs 34%, P = .002). Funding for community support was a common constraint in both countries (49% vs 42%)., Conclusions: The somewhat variable cough effectiveness monitoring and airway clearance practices identified in this survey confirm the need for further work on knowledge translation related to guideline recommendations and the need to address common constraints to optimal service delivery., (Copyright © 2018 by Daedalus Enterprises.)

Background: Pain is prevalent in chronic obstructive pulmonary disease (COPD) and the Brief Pain Inventory (BPI) appears to be a feasible questionnaire to assess this symptom. However, the reliability and validity of the BPI have not been determined in individuals with COPD. This study aimed to determine the internal consistency, test-retest reliability and validity (construct, convergent, divergent and discriminant) of the BPI in individuals with COPD., Methods: In order to examine the test-retest reliability, individuals with COPD were recruited from pulmonary rehabilitation programmes to complete the BPI twice 1 week apart. In order to investigate validity, de-identified data was retrieved from two previous studies, including forced expiratory volume in 1-s, age, sex and data from four questionnaires: the BPI, short-form McGill Pain Questionnaire (SF-MPQ), 36-Item Short Form Survey (SF-36) and Community Health Activities Model Program for Seniors (CHAMPS) questionnaire., Results: In total, 123 participants were included in the analyses (eligible data were retrieved from 86 participants and additional 37 participants were recruited). The BPI demonstrated excellent internal consistency and test-retest reliability. It also showed convergent validity with the SF-MPQ and divergent validity with the SF-36. The factor analysis yielded two factors of the BPI, which demonstrated that the two domains of the BPI measure the intended constructs. The BPI can also discriminate pain levels among COPD patients with varied levels of quality of life (SF-36) and physical activity (CHAMPS)., Conclusion: The BPI is a reliable and valid pain questionnaire that can be used to evaluate pain in COPD., Significance: This study formally established the reliability and validity of the BPI in individuals with COPD, which have not been determined in this patient group. The results of this study provide strong evidence that assessment results from this pain questionnaire are reliable and valid., (© 2018 European Pain Federation - EFIC®.)

Background: Individuals using home mechanical ventilation (HMV) frequently choose to live at home for quality of life, despite financial burden. Previous studies of healthcare utilisation and costs do not consider public and private expenditures, including caregiver time., Objectives: To determine public and private healthcare utilisation and costs for HMV users living at home in two Canadian provinces, and examine factors associated with higher costs., Methods: Longitudinal, prospective observational cost analysis study (April 2012 to August 2015) collecting data on public and private (out-of-pocket, third-party insurance, caregiving) costs every 2 weeks for 6 months using the Ambulatory and Home Care Record. Functional Independence Measure (FIM) was used at baseline and study completion. Regression models examined variables associated with total monthly costs selected a priori using Andersen and Newman's framework for healthcare utilisation, relevant literature, and clinical expertise. Data are reported in 2015 Canadian dollars ($C1=US$0.78=₤0.51=€0.71)., Results: We enrolled 134 HMV users; 95 with family caregivers. Overall median (IQR) monthly healthcare cost was $5275 ($2291-$10 181) with $2410 (58%) publicly funded; $1609 (39%) family caregiving; and $141 (3%) out-of-pocket (<1% third-party insurance). Median healthcare costs were $8733 ($5868-$15 274) for those invasively ventilated and $3925 ($1212-$7390) for non-invasive ventilation. Variables associated with highest monthly costs were amyotrophic lateral sclerosis (1.88, 95% CI 1.09 to 3.26, P<0.03) and lower FIM quintiles (higher dependency) (up to 6.98, 95% CI 3.88 to 12.55, P<0.0001) adjusting for age, sex, tracheostomy and ventilation duration., Conclusions: For HMV users, most healthcare costs were publicly supported or associated with family caregiving. Highest costs were incurred by the most dependent users. Understanding healthcare costs for HMV users will inform policy decisions to optimise resource allocation, helping individuals live at home while minimising caregiver burden., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Purpose: No studies have explored the experiences of Canadian mechanical ventilator-assisted adolescents (VAAs) living at home as they transition from paediatric to adult health providers. A better understanding of the needs of this growing population is essential to provide transition services responsive to VAAs and caregiver-identified needs., Methods: We conducted semistructured telephone interviews with adolescents and family caregivers who had recently initiated or completed transition to adult care recruited from three Canadian university-affiliated paediatric home ventilation programs. We analyzed transcripts using a theoretical framework for understanding facilitators and barriers to transition., Results: We interviewed 18 individuals representing 14 episodes of paediatric to adult transition. Participants identified early planning, written informational materials and joint paediatric-adult provider-family transition meetings as facilitators of care transition to adult services and providers. Barriers included insufficient information, limited access to interprofessional (nursing and allied health) providers and reduced funding or health services. Barriers resulted in service disruption and a sense of 'medical homelessness'. While most families related a positive transition to a new 'medical home', families caring for VAAs with moderate-to-severe cognitive and/or physical dependence more commonly reported transition difficulties., Conclusions: Important opportunities exist to enable improvements in the transition experiences of VAAs and their family caregivers. To maximize service continuity during paediatric to adult transition, future research should focus on transition navigator roles, interprofessional health outreach and the needs of families caring for VAAs with cognitive and physical deficits.

Background: Thoracic computed tomography (CT) scans are widely performed in clinical practice, often leading to detection of airway or parenchymal abnormalities in asymptomatic or minimally symptomatic individuals. However, clinical relevance of CT abnormalities is uncertain in the general population., Methods: We evaluated data from 1361 participants aged ≥40 years from a Canadian prospective cohort comprising 408 healthy never-smokers, 502 healthy ever-smokers, and 451 individuals with spirometric evidence of chronic obstructive pulmonary disease (COPD) who had thoracic CT scans. CT images of subjects were visually scored for respiratory bronchiolitis(RB), emphysema(E), bronchial-wall thickening(BWT), expiratory air-trapping(AT), and bronchiectasis(B). Multivariable logistic regression models were used to assess associations of CT features with respiratory symptoms, dyspnea, health status as determined by COPD assessment test, and risk of clinically significant exacerbations during 12 months follow-up., Results: About 11% of life-time never-smokers demonstrated emphysema on CT scans. Prevalence increased to 30% among smokers with normal lung function and 36%, 50%, and 57% among individuals with mild, moderate or severe/very severe COPD, respectively. Presence of emphysema on CT was associated with chronic cough (OR,2.11; 95%CI,1.4-3.18); chronic phlegm production (OR,1.87; 95% CI,1.27-2.76); wheeze (OR,1.61; 95% CI,1.05-2.48); dyspnoea (OR,2.90; 95% CI,1.41-5.98); CAT score≥10(OR,2.17; 95%CI,1.42-3.30) and risk of ≥2 exacerbations over 12 months (OR,2.17; 95% CI, 1.42-3.0)., Conclusions: Burden of thoracic CT abnormalities is high among Canadians ≥40 years of age, including never-smokers and smokers with normal lung function. Detection of emphysema on CT scans is associated with pulmonary symptoms and increased risk of exacerbations, independent of smoking or lung function., Competing Interests: DDM, JCH, JMF, DOD, MK, CJH, RR, RC, SA, PL, and LZ have no conflict to declare. JL reports consultancy for CT scans vendors GE, Samsung, and Philips. DDS reports personal fees from Almirall, AstraZeneca, Amgen, and Novatis, and grants from AstraZeneca, outside the submitted work. FM reports grants and personal fees from GSK, Boehringer Ingelheim, and Novartis, and grants from Nycomed, and AstraZeneca during the conduct of the study. KRC reports grants from Novartis, Almirall, Boehringer Ingelheim, Forest, GSK, AstraZeneca, Amgen, Roche, CSL Behring, Grifols, Genentech, and Kamada, during the conduct of the study; and other from CIHR-GSK Research Chair in Respiratory Health Care Delivery, outside the submitted work. PH has received fees for delivering accredited CME and/or consultancy on advisory board for AstraZeneca, Boehringer Ingelheim, Bayer, CSL Behring, Grifols, GlaxoSmithKline, Merck, Novartis, Roche. Dr.Hernandez's institution has received funding for conducting research from Boehringer Ingelheim, Grifols, and CSL Behring. HOC reports personal fees from GSK, and Samsung, and grants from GSK, and Spiration Inc, outside the submitted work. JB and WCT report grants from the Canadian Institute of Heath Research (CIHR/Rx&D Collaborative Research Program Operating Grants- 93326) with industry partners Astra Zeneca Canada Ltd., Boehringer-Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd, Merck, Novartis Pharma Canada Inc., Nycomed Canada Inc., and Pfizer Canada Ltd., during the conduct of the study. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Purpose: To non-invasively examine the effect of acute hypoxia and inspiratory threshold loading (ITL) on inspiratory muscles [sternocleidomastoid (SCM), scalene (SA) and parasternal (PS)] oxygenation in healthy adults using near-infrared spectroscopy (NIRS)., Methods: Twenty healthy adults (12 M/8 F) were randomly assigned to perform two ITL tests while breathing a normoxic or hypoxic (FIO2 = 15 %) gas mixture. NIRS devices were placed over the SCM, PS, SA, and a control muscle, tibialis anterior (TA), to monitor oxygenated (O2Hb), deoxygenated (HHb), total hemoglobin (tHb) and tissue saturation index (TSI). With the nose occluded, subjects breathed normally for 4 min through a mouthpiece that was connected to a weighted threshold loading device. ITL began by adding a 100-g weight to the ITL device. Then, every 2 min 50-g was added until task failure. Vital signs, ECG and ventilatory measures were monitored throughout the protocol., Result: Participants were 31 ± 12 year and had normal spirometry. At task failure, the maximum load and ventilatory parameters did not differ between the hypoxic and normoxic ITL. At hypoxic ITL task failure, SpO2 was significantly lower, and ∆HHb increased more so in SA, SCM and PS than normoxic values. SCM ∆TSI decreased more so during hypoxic compared to normoxic ITL. ∆tHb in the inspiratory muscles (SCM, PS and SA) increased significantly compared to the decrease in TA during both hypoxic and normoxic ITL., Conclusion: The SCM, an accessory inspiratory muscle was the most vulnerable to deoxygenation during incremental loading and this response was accentuated by acute hypoxia.

A cardiologist and respirologist examined the recent, neutral Prospective Randomized Placebo-Controlled Trial of Simvastatin in the Prevention of COPD Exacerbations (STATCOPE) for issues of relevance to cardiovascular risk reduction with statin medications. Although the potential benefit of the pleiotropic effects of statins on this inflammatory disease was not borne out, the effect over the longer term on total respiratory and cardiovascular morbidity and mortality remain unexplored. This study was unique as the only statin trial to date to use a national guideline (Adult Treatment Panel III) to exclude patients from the trial if at sufficient cardiovascular risk to warrant statin therapy. Furthermore, observed fatal and nonfatal cardiovascular events were shown to provide some evidence to suggest that statins might reduce cardiovascular events despite the low risk category and the relatively low levels of cholesterol. The magnitude of this beneficial trend paralleled the magnitude of lowering of low-density lipoprotein cholesterol achieved in the active statin arm. Finally, the authors questioned whether the current standard of care adequately includes adherence to any national lipid guideline or adequate attention to the cardiovascular comorbidity of these patients. In conclusion, knowledge translation of the STATCOPE trial should at a minimum encourage assessment of cardiovascular risk in patients with chronic obstructive pulmonary disease, implementation of proven cardiovascular risk reduction therapies based on national guidelines, including statins, and plans to undertake a trial adequate in size and duration to address cardiovascular event reduction in patients not already eligible for evidence-based risk-reducing therapies., (Copyright © 2015 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)