Diaphragm pacing in spinal cord injury can significantly decrease mechanical ventilation in multicenter prospective evaluation.

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.

Incorporating remote patient monitoring in virtual pulmonary rehabilitation programs.

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.

Manipulation of mechanical ventilatory constraint during moderate intensity exercise does not influence dyspnoea in healthy older men and women.

KEY POINTS: The perceived intensity of exertional breathlessness (i.e. dyspnoea) is higher in older women than in older men, possibly as a result of sex-differences in respiratory system morphology. During exercise at a given absolute intensity or minute ventilation, older women have a greater degree of mechanical ventilatory constraint (i.e. work of breathing and expiratory flow limitation) than their male counterparts, which may lead to a greater perceived intensity of dyspnoea. Using a single-blind randomized study design, we experimentally manipulated the magnitude of mechanical ventilatory constraint during moderate-intensity exercise at ventilatory threshold in healthy older men and women. We found that changes in the magnitude of mechanical ventilatory constraint within the physiological range had no effect on dyspnoea in healthy older adults. When older men and women perform moderate intensity exercise, mechanical ventilatory constraint does not contribute significantly to the sensation of dyspnoea. ABSTRACT: We aimed to determine the effect of manipulating mechanical ventilatory constraint during submaximal exercise on dyspnoea in older men and women. Eighteen healthy subjects (aged 60-80 years; nine men and nine women) completed two days of testing. On day 1, subjects were assessed for pulmonary function and performed a maximal incremental cycle exercise test. On day 2, subjects performed three 6-min bouts of cycling at ventilatory threshold, in a single-blind randomized manner, while breathing: (i) normoxic helium-oxygen (HEL) to reduce the work of breathing (Wb ) and alleviate expiratory flow limitation (EFL); (ii) through an inspiratory resistance (RES) of ∼5 cmH2 O L-1  s-1 to increase Wb ; and (iii) ambient air as a control (CON). Oesophageal pressure, diaphragm electromyography, and sensory responses (category-ratio 10 Borg scale) were monitored throughout exercise. During the HEL condition, there was a significant decrease in Wb (men: -21 ± 6%, women: -17 ± 10%) relative to CON (both P < 0.01). Moreover, if EFL was present during CON (four men and five women), it was alleviated during HEL. Conversely, during the RES condition, Wb (men: 42 ± 19%, women: 50 ± 16%) significantly increased relative to CON (both P < 0.01). There was no main effect of sex on Wb (P = 0.59). Across conditions, women reported significantly higher dyspnoea intensity than men (2.9 ± 0.9 vs. 1.9 ± 0.8 Borg scale units, P < 0.05). Despite significant differences in the degree of mechanical ventilatory constraint between conditions, the intensity of dyspnoea was unaffected, independent of sex (P = 0.46). When older men and women perform moderate intensity exercise, mechanical ventilatory constraint does not contribute significantly to the sensation of dyspnoea.

The effects of marijuana smoking on lung function in older people.

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 (FEV1)/forced vital capacity ratio <0.7) in 5291 population-based individuals and the rate of decline in FEV1 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 FEV1 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 FEV1 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 FEV1 decline in concomitant tobacco smokers beyond that observed with tobacco alone.

Healthcare utilisation and costs of home mechanical ventilation.

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.

A Comparison of Pain, Fatigue, Dyspnea and their Impact on Quality of Life in Pulmonary Rehabilitation Participants with Chronic Obstructive Pulmonary Disease.

In addition to dyspnea and fatigue, pain is a prevalent symptom in chronic obstructive pulmonary disease (COPD). Understanding the relative prevalence, magnitude, and interference with aspects of daily living of these symptoms can improve COPD management. Therefore, the purposes of this study were to: (1) compare the prevalence and magnitude of dyspnea, fatigue, and pain and how each limits aspects of daily living; (2) determine the association between pain and the other two symptoms; and (3) assess the impact of these symptoms on quality of life in COPD. Participants were recruited from pulmonary rehabilitation programs. Pain, dyspnea, and fatigue were measured using the Brief Pain Inventory (BPI), Brief Fatigue Inventory (BFI), and Dyspnea Inventory (DI), respectively. Quality of life was measured using the Clinical COPD Questionnaire (CCQ). The prevalence of dyspnea, fatigue, and pain were 93%, 77%, and 74%, respectively. Individuals with COPD reported similar severity scores of the three symptoms. Dyspnea interfered with general activity more than pain (F1.7,79.9 = 3.1, p < 0.05), whilst pain interfered with mood (F1.8, 82.7 = 3.6, p < 0.05) and sleep (F1,46 = 7.4, p < 0.01) more than dyspnea and fatigue. These three symptoms were moderately-to-highly correlated with each other (ρ = 0.49-0.78, p < 0.01) and all individually impacted quality of life. In summary, pain is a common symptom in addition to dyspnea and fatigue in COPD; all three interfere similarly among aspects of daily living with some exceptions. Accordingly, management of COPD should include a multifaceted approach that addresses pain as well as dyspnea and fatigue.

Framing of mobility items: a source of poor agreement between preference-based health-related quality of life instruments in a population of individuals receiving assisted ventilation.

PURPOSE: To explore the influence of descriptive differences in items evaluating mobility on index scores generated from two generic preference-based health-related quality of life (HRQoL) instruments. METHODS: The study examined cross-sectional data from a postal survey of individuals receiving assisted ventilation in two state/province-wide home mechanical ventilation services, one in British Columbia, Canada and the other in Victoria, Australia. The Assessment of Quality of Life 8-dimension (AQoL-8D) and the EQ-5D-5L were included in the data collection. Graphical illustrations, descriptive statistics, and measures of agreement [intraclass correlation coefficients (ICCs) and Bland-Altman plots] were examined using index scores derived from both instruments. Analyses were performed on the full sample as well as subgroups defined according to respondents' self-reported ability to walk. RESULTS: Of 868 individuals receiving assisted ventilation, 481 (55.4%) completed the questionnaire. Mean index scores were 0.581 (AQoL-8D) and 0.566 (EQ-5D-5L) with 'moderate' agreement demonstrated between the two instruments (ICC = 0.642). One hundred fifty-nine (33.1%) reported level 5 ('I am unable to walk about') on the EQ-5D-5L Mobility item. The walking status of respondents had a marked influence on the comparability of index scores, with a larger mean difference (0.206) and 'slight' agreement (ICC = 0.386) observed when the non-ambulant subgroup was evaluated separately. CONCLUSIONS: This study provides further evidence that between-measure discrepancies between preference-based HRQoL instruments are related in part to the framing of mobility-related items. Longitudinal studies are necessary to determine the responsiveness of preference-based HRQoL instruments in cohorts that include non-ambulant individuals.

Comorbidities That Cause Pain and the Contributors to Pain in Individuals With Chronic Obstructive Pulmonary Disease.

OBJECTIVE: To determine comorbidities that cause pain and the potential contributors to pain in individuals with chronic obstructive pulmonary disease (COPD). DESIGN: Prospective cross-sectional survey study. SETTING: Pulmonary rehabilitation programs of 6 centers. PARTICIPANTS: A convenience sample of individuals with COPD (N=137) who attended pulmonary rehabilitation programs. In total, 100 (73%) returned the survey packages. Of those responders, 96 participants (70%) were included in the analyses. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Pain was measured using the Brief Pain Inventory. The questionnaire used to obtain information about health conditions that might contribute to pain and a medication record asked, in lay terms, about comorbidities that cause pain. The health conditions that cause pain were then validated by health professionals. Demographics, fatigue, dyspnea, quality of life, and self-efficacy were also measured using questionnaires. RESULTS: Pain was reported in 71% (68/96) of participants. Low back pain was the most common location (41%). Arthritis (75%), back problems (47%), and muscle cramps (46%) were the most common comorbidities that caused pain. Lower self-efficacy, and renting rather than home ownership increased the likelihood of pain (P<.05). Pain severity and Brief Fatigue Inventory scores contributed to pain interference scores (P<.05). CONCLUSIONS: Pain was highly prevalent in pulmonary rehabilitation program participants with COPD. The most common causes of pain were musculoskeletal conditions. Pain severity and higher levels of fatigue contributed to how pain interfered with daily aspects of living. The assessment and management of pain need to be addressed within the overall care of individuals with COPD.

Health transition experiences of Canadian ventilator-assisted adolescents and their family caregivers: A qualitative interview study.

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.

Effect of acute hypoxia on inspiratory muscle oxygenation during incremental inspiratory loading in healthy adults.

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.

In vivo dopaminergic and serotonergic dysfunction in DCTN1 gene mutation carriers.

INTRODUCTION: We used positron emission tomography (PET) to assess dopaminergic and serotonergic terminal density in three subjects carrying a mutation in the DCT1 gene, two clinically affected with Perry syndrome. METHODS: All subjects had brain imaging using 18F-6-fluoro-l-dopa (FDOPA, dopamine synthesis and storage), (+)-11C-dihydrotetrabenazine (DTBZ, vesicular monoamine transporter type 2), and 11C-raclopride (RAC, dopamine D2/D3 receptors). One subject also underwent PET with 11C-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile (DASB, serotonin transporter). RESULTS: FDOPA-PET and DTBZ-PET in the affected individuals showed a reduction of striatal tracer uptake. Also, RAC-PET showed higher uptake in these area. DASB-PET showed significant uptake changes in left orbitofrontal cortex, bilateral anterior insula, left dorsolateral prefrontal cortex, left orbitofrontal cortex, left posterior cingulate cortex, left caudate, and left ventral striatum. CONCLUSIONS: Our data showed evidence of both striatal dopaminergic and widespread cortical/subcortical serotonergic dysfunctions in individuals carrying a mutation in the DCTN1 gene.

Gaseous nitric oxide reduces influenza infectivity in vitro.

Gaseous nitric oxide (gNO) is an approved vasodilator drug for inhalation up to a maximum dose of 80 ppm. While gNO has been shown, in vitro, to be an effective antibacterial agent (at 160 ppm), NO-donor compounds have been shown to inhibit a variety of viruses at varying stages of replication. This research was done in order to determine whether gNO at 80 or 160 ppm possesses an antiviral effect on influenza viruses. Three strains of influenza (A and B) were exposed to gNO for up to 180 min, before and after infection of MDCK cells. In search for possible mechanism of antiviral action, Neuraminidase (NA) inhibition assay of H1N1 that was exposed to gNO was performed. Results show that when virions were exposed to gNO prior to infection a complete inhibition of infectivity was achieved for all three strains. Post infection exposure of influenza with gNO resulted in about 30% inhibition of infectivity. Further testing showed that when eliminating the pH effect by exposing a dried virus to gNO, 90% inhibition was found after 2h exposure. NA activity, of whole dried H1N1 virus, was found to be inhibited by gNO (80%). These results suggest that 80 and 160 ppm gNO have a time dependent antiviral effect on influenza strains of viruses during various stages of cellular infection, which are not due to concomitant changes in pH in the surrounding milieu. Viral NA inhibition by gNO was shown and may be responsible for this antiviral effect.

Noninvasive Home Mechanical Ventilation for Stable Hypercapnic COPD: A Clinical Respiratory Review from Canadian Perspectives.

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 (PaCO2) 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.

Factors Associated with Attrition in a Longitudinal Cohort of Older Adults in the Community.

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.

Serum skeletal troponin I following inspiratory threshold loading in healthy young and middle-aged men.

The purpose of this study was to determine if serum levels of skeletal troponin I (sTnI, fast and slow isoforms) could provide a sensitive marker of respiratory muscle damage in healthy humans subjected to inspiratory loads. To accomplish this, we studied healthy, young (27 ± 2 years, Mean ± SEM, n = 5) and middle-aged (55 ± 5, n = 5) men to (1) determine the magnitude, pattern, and time course of the presence of sTnI in the serum after a single 60 min bout of inspiratory threshold loading [ITL, ~70% of maximal inspiratory pressure (MIP)], (2) determine the distribution and magnitude of DOMS after loading, and (3) compare fast and slow sTnI levels, and their relationship to other markers/indices of muscle injury including delayed onset muscle soreness (DOMS), serum creatine kinase (CK) levels, and force generating capacity of the respiratory muscles [MIP and maximal expiratory pressure (MEP)]. There was a 24 ± 4 and 27 ± 3% increase in fast sTnI 1 hour (p < 0.01) and 3 days (p < 0.01) after ITL. Slow sTnI was elevated by 24 ± 10% (p < 0.05) 4 days postITL. Other indices of respiratory muscle injury such as CK, MIP and MEP did not show a difference in mean data following ITL; DOMS was slightly but significantly increased following ITL. Our results suggest that sTnI has superior sensitivity compared to other biomarkers/indices of skeletal muscle injury. Future studies examining the impact of respiratory muscle injury with ventilator weaning should consider using sTnI as a sensitive marker of skeletal muscle injury.

The experience of family caregivers of ventilator-assisted individuals who participated in a pilot web-based peer support program: A qualitative study.

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.

The Prevalence of Chronic Obstructive Pulmonary Disease (COPD) and the Heterogeneity of Risk Factors in the Canadian Population: Results from the Canadian Obstructive Lung Disease (COLD) Study.

PURPOSE: To determine the spirometric-based prevalence of COPD across different regions in Canada and to evaluate the site heterogeneity of risk factors. PATIENTS AND METHODS: In this cross-sectional, population-based study, random samples of non-institutionalized adults aged ≥40 years were generated by random digit dialling. Participants answered an interviewer-administered questionnaire and performed spirometry before and after bronchodilator administration. COPD was defined as post-bronchodilator FEV1/FVC <0.70 (fixed ratio, FR) and as FEV1/FVC <5th percentile (lower limits of normal, LLN). Separate logistic regression models were used to compute the risk (adjusted odds ratio, aOR) for COPD. I2 and Tau2 analyses were used to evaluate heterogeneity. RESULTS: Out of 5176 (95%) participants, 4893 (47% male with mean age 56.6 years (95% confidence interval, 56.0-57.2)) had spirometry that satisfied ATS criteria. The population prevalence of COPD was 16.2% (95% CI, 14.5-17.8) by FR and 11.2% (95% CI, 9.7-12.6) by LLN. Male predominance in prevalence was shown by FR but not by LLN criteria. Patient characteristics associated with an increased risk of COPD included: age (OR 1.56; 95% CI 1.33-1.84); history of physician-diagnosed asthma (OR 3.30; 95% CI 2.42-4.49); and childhood hospitalization for respiratory illness (OR 1.81; 95% CI 1.17-2.80). In terms of smoking-related risk factors, current smoking status had the highest odds ratio (OR 3.49; 95% CI 2.55-4.80). Variance in prevalence among sites was significantly reduced by adjusting for risk factors in Tau2 analyses. Higher odds of exposure for each risk factor was found in more severe COPD, suggesting that a higher risk could be linked to the development of severe disease. CONCLUSION: This study reports the population prevalence of COPD in nine urban cities which collectively represent the majority of the Canadian population and demonstrates that heterogeneity in prevalence among sites is substantially explained by variation in associated risk factors for COPD.

Evaluation of the Vibe Actigraph in Patients With Chronic Obstructive Pulmonary Disease: A Pilot Study.

STUDY OBJECTIVE: To validate the Vibe actigraph in assessing sleep-wake patterns compared to polysomnography (PSG) in patients with COPD. METHODS: Nine stable COPD patients wore actigraphs while undergoing PSG. The correlation between total sleep time (TST), total sleep period (TSP), sleep onset latency (SOL), wake after sleep onset (WASO), and sleep efficiency was determined for corresponding measurements from the actigraph and PSG. Sensitivity, specificity, and positive and negative predictive values were calculated for the actigraph, considering PSG the gold standard. Levels of agreement between the variables of PSG and the actigraph were estimated using Bland-Altman plots. RESULTS: A strong and statistically significant correlation was noted between PSG and the actigraph in detecting movement during sleep [mean activity score (counts)], TST and TSP (all rs = 0.83; p = 0.005). The median agreement of sleep and wake counts between PSG and the actigraph was 73% and the Cohen's Kappa value was 0.66. The medians of sensitivity and specificity of the actigraph for detecting sleep versus PSG were 84 and 66%, respectively. The median positive and negative predictive values of the actigraph were 74 and 72%, respectively. CONCLUSIONS: This study demonstrated that, under controlled laboratory conditions, the Vibe actigraph in its default settings is a promising tool for the detection of sleep-wake parameters in a small number of ambulatory patients with COPD. Clinical Impact: The actigraph used in this pilot study suggests that these devices could provide clinically relevant information in COPD to better understand the relationship between sleep and health in this population.

Scalene and sternocleidomastoid activation during normoxic and hypoxic incremental inspiratory loading.

The purpose of this study was to examine scalene (SA) and sternocleidomastoid (SM) activation during normoxic (norm-ITL; FIO2  = 21%) and hypoxic (hyp-ITL; FIO2  = 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.

Gaseous nitric oxide bactericidal activity retained during intermittent high-dose short duration exposure.

Previously, we have shown that gaseous Nitric oxide (gNO) has great potential as an effective topical anti-infective agent for non-healing wounds due to its non-specific antimicrobial properties. These same antimicrobial attributes may be useful for pulmonary infections. However, gNO would have limited usefulness as an inhaled antimicrobial agent as continuous exposure to the concentration required for a bactericidal effect (160-200 ppm) leads to methemoglobinemia. To overcome this problem, we investigated whether a thirty minute exposure of 160 ppm every four hours would retain the same antimicrobial effect as continuous delivery. In vitro, exposure of clinical multi-drug resistant Staphylococcus aureus and Escherichia coli strains isolated from the lungs of nosocomial pneumonia patients and a lethal antibiotic-resistant strain of Pseudomonas aeruginosa, isolated from a deceased cystic fibrosis patient resulted in over a 5 log(10) reduction in bacterial load after multiple thirty minute treatments (4 cycles) every four hours to 160 ppm gNO. The intermittent regimen required 320 (SD=0)ppm h for 100% lethality whereas the continuous exposure required 800 (SD=160)ppm h. We have also shown that selection for a gNO resistant phenotype did not lead to decrease sensitivity to gNO therapy (p>0.05). In addition, no host cellular toxicity was observed in human THP-1 monocytes and macrophages following intermittent delivery of a high concentration of gNO, and the proliferation and migration of pulmonary epithelial cells was not adversely affected by the administration of intermittent high-dose gNO. These results justify further studies that should focus on whether intermittent delivery of 160 ppm of gNO every four hours can technically be administered while keeping inhaled NO(2) levels less than 2 ppm and methemoglobin saturation less than 2.5 percent.