Feasibility and performance of the chronic obstructive pulmonary disease population screener and chronic obstructive pulmonary disease screening questionnaire in a Chinese physical examination center.

Background: Chronic obstructive pulmonary disease (COPD) affects up to 13% of the Chinese population, though it is under diagnosed throughout China. Screening among asymptomatic individual as part of routine health checks in China can facilitate early diagnosis and intervention to prevent disease progress. The COPD Population Screener (COPD-PS) or COPD Screening Questionnaire (COPD-SQ) has yet to be applied in Chinese physical examination centers (PECs) for COPD screening, and their feasibility and effectiveness should be clarified before full-scale implementation. This study is the first to apply the COPD-PS and COPD-SQ in a public hospital PEC in China to assess their feasibility and effectiveness and to identify their optimal cutoff values. Methods: People aged ≥40 years who attended the Second Affiliated Hospital of Shantou University PECs from September 2021 to December 2022 were asked to complete the COPD-PS and COPD-SQ and to undergo spirometry. The optimal cutoff values of the two questionnaires at the maximal Youden index were found, and the sensitivity and specificity were calculated. Results: Data from 198 participants were analyzed; mean [standard deviation (SD)] age of patients was 63.52 (10.94) years. Twenty-five participants (12.63%) were diagnosed with COPD. The number of COPD patients classified as Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 1 to 4 were 8, 12, 4, and 1, respectively. The area under the curves (AUCs) of the COPD-PS and COPD-SQ were 0.730 and 0.738, respectively. The optimal COPD-PS cutoff value of 4 points corresponded to a sensitivity of 72.00% and a specificity of 60.10%. The COPD-SQ optimal cutoff value of 15 points corresponded to a sensitivity of 76.00% and a specificity of 63.60%. Conclusions: Applying the COPD-PS and COPD-SQ in Chinese PECs is feasible, cost-effective and effective. COPD-PS and COPD-SQ can facilitate the early diagnosis of COPD, and whether they can improve the participants' quality of life would benefit a further study. It is recommended that the COPD-PS or COPD-SQ questionnaires be added to the screening of the physical examination program in PECs as part of health checks for people over 40 years old.

Qualitative assessment of sensations and triggers in chronic cough.

Qualitative interviews show a wide range of cough triggers and sensations in patients with refractory chronic cough. Knowledge of these may help us manage this complicated and impactful condition. https://bit.ly/41k9Ot5.

Practicality and Safety of Electrical Pulmonary Vein Isolation and Left Atrial Appendage Ligation in Lung Transplant Recipients With Pretransplant Atrial Fibrillation.

Background: Lung transplant surgery creates surgical pulmonary vein isolation (PVI) as a routine part of the procedure. However, many patients with pretransplant atrial fibrillation continue to have atrial fibrillation at 1 y. We hypothesized that the addition of electrical PVI and left atrial appendage isolation/ligation (LAL) to the lung transplant procedure restores sinus rhythm at 1 y in patients with pretransplant atrial fibrillation. Methods: We retrospectively reviewed all adult lung transplant recipients at the University of California Los Angeles from April 2006 to August 2021. All patients with pretransplant atrial fibrillation underwent concomitant PVI/LAL and were compared with lung transplant recipients without preoperative atrial fibrillation. In-hospital outcomes; 1-y survival; and the incidence of stroke, cardiac readmissions, repeat ablations, and sinus rhythm (composite endpoint) were examined at 1 y for the PVI/LAL cohort. Results: Sixty-one lung transplant recipients with pretransplant atrial fibrillation underwent concomitant PVI/LAL. No patient in the PVI/LAL cohort required cardiac-related readmission or catheter ablation for atrial fibrillation within 1 y of transplantation. Freedom from the composite endpoint of death, stroke, cardiac readmission, and repeat ablation for atrial fibrillation at 1 y was 85% (95% confidence interval, 73%-92%) for lung transplant recipients treated with PVI/LAL. Conclusions: The addition of PVI/LAI to the lung transplant operation in patients with pretransplant atrial fibrillation was safe and effective in maintaining sinus rhythm and baseline risk of stroke at 1 y.

Cough in chronic lung disease: a state of the art review.

Chronic cough (CC; ≥8 weeks in duration) is a common and burdensome feature of respiratory diseases. The understanding of cough has progressed significantly in recent years, albeit largely in refractory (unexplained) chronic cough (RCC) in the absence of other respiratory conditions. The prevalence of CC in respiratory diseases is poorly described, but estimates have been reported: asthma (8-58%), chronic obstructive pulmonary disease (COPD; 10-74%), bronchiectasis (82-98%), interstitial lung disease (ILD; 50-89%) and sarcoidosis (3-64%). CC in respiratory conditions generally predicts impaired health status and more severe disease. It is associated with increased symptom burden and disease severity in asthma, COPD, bronchiectasis and ILD, higher exacerbation frequency in asthma and bronchiectasis, and increased mortality and lung transplantation in idiopathic pulmonary fibrosis (IPF). Physiologically, heightened cough reflex sensitivity (CRS) has been reported and postulated to be mechanistic in isolated RCC. Cough reflex hypersensitivity (CRH) has also been reported in asthma, COPD, bronchiectasis, ILD and sarcoidosis. Unlike recent advances in isolated RCC, there are limited studies and understanding of central cough neuropathways in other respiratory conditions. Of note, dysfunctional central voluntary cough suppression neuropathways and physiology were observed in isolation in RCC; cough suppression is preserved in COPD. Understanding in the mechanism of RCC cannot be simply extrapolated to other respiratory conditions. The restricted understanding of cough mechanisms in these conditions has limited cough-specific therapeutic options in this context. There is currently an unmet need to expand our understanding of cough in chronic respiratory conditions, both in order to improve the quality of life of patients, and to improve knowledge of cough in general. This review aims to describe the prevalence, impact, pathophysiology and management of CC in asthma, COPD, bronchiectasis, ILD and sarcoidosis.

Patient Global Impression of Severity Scale in Chronic Cough: Validation and Formulation of Symptom Severity Categories.

BACKGROUND: The Patient Global Impression of Severity (PGI-S) scale is a self-reported, single-item categorical scale that is increasingly used when assessing chronic cough (CC). OBJECTIVE: This study aimed to establish validity, repeatability, and responsiveness of the PGI-S scale in CC and use the scale to define discrete categories of severity when measured with other commonly used patient-reported outcome (PRO) tools. METHODS: Consecutive patients with CC completed the PGI-S scale, cough severity and urge to cough visual analog scales (VAS), and cough-specific health status Leicester Cough Questionnaire (LCQ) at a clinic visit. Validity, repeatability, and responsiveness were assessed, and threshold scores for PRO severity categories determined. RESULTS: A total of 482 participants completed the assessments; the median (interquartile range [IQR]) age was 57 (46-67) years, 71% were female, and the median (IQR) duration of cough was 48 (24-120) months. They reported a median (IQR) PGI-S score of 3 (3-4; moderate severity), cough severity VAS of 57 (31-75) mm, urge to cough VAS of 62 (40-81) mm, and LCQ of 11.5 (8.7-14.4). There were strong associations between PGI-S scores and cough severity VAS (ρ = 0.81), urge to cough VAS (ρ = 0.73), and LCQ (ρ = -0.73) (all P < .001). Repeatability of the PGI-S scale was high (n = 77); the intraclass correlation coefficient (95% confidence interval) was 0.85 (0.77-0.91) (P < .001). The PGI-S scale was responsive in participants with a treatment response (P < .001). The suggested PRO thresholds to define severe cough are ≥61 mm (cough severity VAS), ≥71 mm (urge to cough VAS), and ≤10 (LCQ). CONCLUSION: The PGI-S scale is a simple and valid tool that characterizes cough severity and is repeatable and responsive in CC. The proposed categorical severity thresholds for VAS and LCQ can provide intuitive meaning for patients and clinicians.

Safety and efficacy of delaying lung transplant surgery to a morning start.

Objective: We aimed to evaluate the safety and efficacy of delaying lung transplantation until morning for donors with cross-clamp times occurring after 1:30 am. Methods: All consented adult lung transplant recipients between March 2018 and May 2022 with donor cross-clamp times between 1:30 am and 5 am were enrolled prospectively in this study. Skin incision for enrolled recipients was delayed until 6:30 am (Night group). The control group was identified using a 1:2 logistic propensity score method and included recipients of donors with cross-clamp times occurring at any other time of day (Day group). Short- and medium-term outcomes were examined between groups. The primary endpoint was early mortality (30-day and in-hospital). Results: Thirty-four patients were enrolled in the Night group, along with 68 well-matched patients in the Day group. As expected, donors in the Night group had longer cold ischemia times compared to the Day group (344 minutes vs 285 minutes; P < .01). Thirty-day mortality (3% vs 3%; P = .99), grade 3 primary graft dysfunction at 72 hours (8% vs 4%; P = .40), postoperative complications (26% vs 38%; P = .28), and hospital length of stay (15 days vs 14 days; P = .91) were similar in the 2 groups. No significant differences were noted between groups in 3-year survival (70% vs 77%; P = .30) or freedom from chronic lung allograft dysfunction (91% vs 95%; P = .75) at 3 years post-transplantation. The median follow-up was 752.5 days (interquartile range, 487-1048 days). Conclusions: Lung transplant recipients with donor cross-clamp times scheduled after 1:30 am may safely have their operations delayed until 6:30 am with acceptable outcomes. Adoption of such a policy in clinically appropriate settings may lead to an alternative workflow and improved team well-being.

Chronic cough: is the end nigh?

Chronic cough (lasting more than 8 weeks) is a common condition with substantial psychosocial impact. Despite huge efforts following robust guidelines, chronic cough in many patients remains refractory or unexplained (RU-CC). Recent insights support a significant role for cough hypersensitivity in RU-CC, including neuropathophysiological evidence from inhalational cough challenge testing, functional magnetic resonance imaging, and airway nerve biopsy. Along with improved approaches to measuring cough, this knowledge has developed in tandem with repurposing neuromodulator medications, including gabapentin, and evidence for non-pharmacological treatments. Most significantly, there is now a pipeline for novel classes of drugs specifically for chronic cough. The P2X3 receptor antagonist gefapixant is the first such drug to be approved in Europe. However, challenges persist. The field of chronic cough needs more robust epidemiological data, enhanced diagnostic tools, further well-designed clinical trials accounting for the effects of placebo, and treatments with minimal side-effects. Addressing these challenges are novel chronic cough registries, improved International Classification of Diseases (10th revision) coding, genetic testing options and further mechanistic studies. This Viewpoint article discusses these facets and considers how, whilst the end of chronic cough may not be imminent for all patients, the evolving landscape looks increasingly optimistic.

A method for intelligent allocation of diagnostic testing by leveraging data from commercial wearable devices: a case study on COVID-19.

Mass surveillance testing can help control outbreaks of infectious diseases such as COVID-19. However, diagnostic test shortages are prevalent globally and continue to occur in the US with the onset of new COVID-19 variants and emerging diseases like monkeypox, demonstrating an unprecedented need for improving our current methods for mass surveillance testing. By targeting surveillance testing toward individuals who are most likely to be infected and, thus, increasing the testing positivity rate (i.e., percent positive in the surveillance group), fewer tests are needed to capture the same number of positive cases. Here, we developed an Intelligent Testing Allocation (ITA) method by leveraging data from the CovIdentify study (6765 participants) and the MyPHD study (8580 participants), including smartwatch data from 1265 individuals of whom 126 tested positive for COVID-19. Our rigorous model and parameter search uncovered the optimal time periods and aggregate metrics for monitoring continuous digital biomarkers to increase the positivity rate of COVID-19 diagnostic testing. We found that resting heart rate (RHR) features distinguished between COVID-19-positive and -negative cases earlier in the course of the infection than steps features, as early as 10 and 5 days prior to the diagnostic test, respectively. We also found that including steps features increased the area under the receiver operating characteristic curve (AUC-ROC) by 7-11% when compared with RHR features alone, while including RHR features improved the AUC of the ITA model's precision-recall curve (AUC-PR) by 38-50% when compared with steps features alone. The best AUC-ROC (0.73 ± 0.14 and 0.77 on the cross-validated training set and independent test set, respectively) and AUC-PR (0.55 ± 0.21 and 0.24) were achieved by using data from a single device type (Fitbit) with high-resolution (minute-level) data. Finally, we show that ITA generates up to a 6.5-fold increase in the positivity rate in the cross-validated training set and up to a 4.5-fold increase in the positivity rate in the independent test set, including both symptomatic and asymptomatic (up to 27%) individuals. Our findings suggest that, if deployed on a large scale and without needing self-reported symptoms, the ITA method could improve the allocation of diagnostic testing resources and reduce the burden of test shortages.

A Method for Intelligent Allocation of Diagnostic Testing by Leveraging Data from Commercial Wearable Devices: A Case Study on COVID-19.

Mass surveillance testing can help control outbreaks of infectious diseases such as COVID-19. However, diagnostic test shortages are prevalent globally and continue to occur in the US with the onset of new COVID-19 variants, demonstrating an unprecedented need for improving our current methods for mass surveillance testing. By targeting surveillance testing towards individuals who are most likely to be infected and, thus, increasing testing positivity rate (i.e., percent positive in the surveillance group), fewer tests are needed to capture the same number of positive cases. Here, we developed an Intelligent Testing Allocation (ITA) method by leveraging data from the CovIdentify study (6,765 participants) and the MyPHD study (8,580 participants), including smartwatch data from 1,265 individuals of whom 126 tested positive for COVID-19. Our rigorous model and parameter search uncovered the optimal time periods and aggregate metrics for monitoring continuous digital biomarkers to increase the positivity rate of COVID-19 diagnostic testing. We found that resting heart rate features distinguished between COVID-19 positive and negative cases earlier in the course of the infection than steps features, as early as ten and five days prior to the diagnostic test, respectively. We also found that including steps features increased the area under the receiver operating characteristic curve (AUC-ROC) by 7-11% when compared with RHR features alone, while including RHR features improved the AUC of the ITA model's precision-recall curve (AUC-PR) by 38-50% when compared with steps features alone. The best AUC-ROC (0.73 ± 0.14 and 0.77 on the cross-validated training set and independent test set, respectively) and AUC-PR (0.55 ± 0.21 and 0.24) were achieved by using data from a single device type (Fitbit) with high-resolution (minute-level) data. Finally, we show that ITA generates up to a 6.5-fold increase in the positivity rate in the cross-validated training set and up to a 3-fold increase in the positivity rate in the independent test set, including both symptomatic and asymptomatic (up to 27%) individuals. Our findings suggest that, if deployed on a large scale and without needing self-reported symptoms, the ITA method could improve allocation of diagnostic testing resources and reduce the burden of test shortages.

Healthcare utilization and costs in chronic cough.

BACKGROUND: Chronic cough is a common reason for medical consultations and is associated with considerable physical and psychological morbidity. This study investigated healthcare use and cost in chronic cough and assessed its relationship with cough severity, health status, objective cough frequency (CF), and anxiety and depression. METHODS: This was a prospective study of consecutive patients with chronic cough from a specialist clinic who completed a cough severity visual analogue scale (VAS), cough-specific health status (Leicester Cough Questionnaire; LCQ) and general health status EuroQol EQ-5D-5L, Generalized Anxiety Disorder (GAD7), Patient Health Questionnaire (PHQ9), and 24-hour objective CF monitoring with Leicester Cough Monitor (LCM). Case notes were reviewed for cough-specific healthcare use 12 months before and after the first cough clinic consultation. Resource use included general practitioner and hospital clinic visits, investigations, and treatments. Unit costs for healthcare use were derived predominantly from National Health Service Reference Costs. RESULTS: One hundred participants with chronic cough were recruited (69% female, median duration 3 years, mean age 58 years). The diagnoses of cough were unexplained (57%), refractory (27%), and other (16%). Cough severity, health status, and CF were: median (IQR) VAS = 59.5 (30-79) mm, mean (SD) LCQ = 11.9 (4.0), mean (SD) EQ-5D-5L = 0.846 (0.178), and geometric mean (SD) CF = 15.3 (2.5) coughs/hr, respectively. The mean (SD) total cost per individual for cough-related healthcare utilization was £1,663 (747). Diagnostic investigations were the largest contributor to cost (63%), followed by cough clinic consultations (25%). In multivariate analysis, anxiety (GAD7) and cough-related health status (LCQ) were associated with increased cost (p ≤.001 and .037). CONCLUSION: Healthcare cost associated with chronic cough are largely due to diagnostic investigations and clinic consultations. The predictors of costs were health status (LCQ) and anxiety. Further studies should investigate the optimal management protocols for patients with chronic cough.

Noninvasive Assessment of Neuromechanical and Neuroventilatory Coupling in COPD.

This study explored the use of parasternal second intercostal space and lower intercostal space surface electromyogram (sEMG) and surface mechanomyogram (sMMG) recordings (sEMGpara and sMMGpara, and sEMGlic and sMMGlic, respectively) to assess neural respiratory drive (NRD), neuromechanical (NMC) and neuroventilatory (NVC) coupling, and mechanical efficiency (MEff) noninvasively in healthy subjects and chronic obstructive pulmonary disease (COPD) patients. sEMGpara, sMMGpara, sEMGlic, sMMGlic, mouth pressure (Pmo), and volume (Vi) were measured at rest, and during an inspiratory loading protocol, in 16 COPD patients (8 moderate and 8 severe) and 9 healthy subjects. Myographic signals were analyzed using fixed sample entropy and normalized to their largest values (fSEsEMGpara%max, fSEsMMGpara%max, fSEsEMGlic%max, and fSEsMMGlic%max). fSEsMMGpara%max, fSEsEMGpara%max, and fSEsEMGlic%max were significantly higher in COPD than in healthy participants at rest. Parasternal intercostal muscle NMC was significantly higher in healthy than in COPD participants at rest, but not during threshold loading. Pmo-derived NMC and MEff ratios were lower in severe patients than in mild patients or healthy subjects during threshold loading, but differences were not consistently significant. During resting breathing and threshold loading, Vi-derived NVC and MEff ratios were significantly lower in severe patients than in mild patients or healthy subjects. sMMG is a potential noninvasive alternative to sEMG for assessing NRD in COPD. The ratios of Pmo and Vi to sMMG and sEMG measurements provide wholly noninvasive NMC, NVC, and MEff indices that are sensitive to impaired respiratory mechanics in COPD and are therefore of potential value to assess disease severity in clinical practice.

Demographic Imbalances Resulting From the Bring-Your-Own-Device Study Design.

Digital health technologies, such as smartphones and wearable devices, promise to revolutionize disease prevention, detection, and treatment. Recently, there has been a surge of digital health studies where data are collected through a bring-your-own-device (BYOD) approach, in which participants who already own a specific technology may voluntarily sign up for the study and provide their digital health data. BYOD study design accelerates the collection of data from a larger number of participants than cohort design; this is possible because researchers are not limited in the study population size based on the number of devices afforded by their budget or the number of people familiar with the technology. However, the BYOD study design may not support the collection of data from a representative random sample of the target population where digital health technologies are intended to be deployed. This may result in biased study results and biased downstream technology development, as has occurred in other fields. In this viewpoint paper, we describe demographic imbalances discovered in existing BYOD studies, including our own, and we propose the Demographic Improvement Guideline to address these imbalances.

Engineering digital biomarkers of interstitial glucose from noninvasive smartwatches.

Prediabetes affects one in three people and has a 10% annual conversion rate to type 2 diabetes without lifestyle or medical interventions. Management of glycemic health is essential to prevent progression to type 2 diabetes. However, there is currently no commercially-available and noninvasive method for monitoring glycemic health to aid in self-management of prediabetes. There is a critical need for innovative, practical strategies to improve monitoring and management of glycemic health. In this study, using a dataset of 25,000 simultaneous interstitial glucose and noninvasive wearable smartwatch measurements, we demonstrated the feasibility of using noninvasive and widely accessible methods, including smartwatches and food logs recorded over 10 days, to continuously detect personalized glucose deviations and to predict the exact interstitial glucose value in real time with up to 84% and 87% accuracy, respectively. We also establish methods for designing variables using data-driven and domain-driven methods from noninvasive wearables toward interstitial glucose prediction.

Multiple-dose pharmacokinetics and opioid effects of a novel analgesic with a deterrent to human opioid abuse (methadone-fluconazole-naltrexone) after oral administration in dogs.

OBJECTIVE: To assess the pharmacokinetics and opioid effects of methadone after administration of multiple doses by means of 2 dosing regimens of methadone-fluconazole-naltrexone. ANIMALS: 12 healthy Beagles. PROCEDURES: Dogs were randomly allocated (6 dogs/group) to receive 1 of 2 oral dosing regimens of methadone-fluconazole-naltrexone. Treatment 1 doses were administered at 0 (methadone-to-fluconazole-to-naltrexone ratio of 1:5:0.25 mg/kg), 14 (1:5:0.25), 24 (0.5:2.5:0.125), and 38 (0.5:2.5:0.125) hours. Treatment 2 doses were administered at 0 (1:5:0.25), 4 (0.5:2.5:0.125), 10 (0.5:2.5:0.125), and 24 (0.5:2.5:0.125) hours. Blood samples, rectal temperatures, and von Frey antinociceptive measurements were obtained at designated times. RESULTS: Compared with baseline, temperatures significantly decreased for treatment 1 group dogs at 2 to ≥ 4 hours and from 16 to ≥ 50 hours (12 hours after last dose) and for treatment 2 group dogs at 2 to ≥ 36 hours (12 hours after last dose), when trough methadone concentrations were ≥ 21.3 ng/mL. Antinociception occurred after the first dose but was not maintained throughout the study. Lesions were noted in some dogs at the application site of the von Frey device. Naltrexone and ß-naltrexol were sporadically detected in plasma, and naltrexone glucuronide was consistently detected. CONCLUSIONS AND CLINICAL RELEVANCE: Opioid effects were noted after oral administration of the first dose, and data suggested that administering a second dose 6 hours later and every 12 hours thereafter was necessary to maintain opioid effects. Antinociception may have been lost because dogs became averse or hyperalgesic to the von Frey device, such that the antinociception model used here may not be robust for repeated measurements in dogs.

Non-invasive wearables for remote monitoring of HbA1c and glucose variability: proof of concept.

INTRODUCTION: Diabetes prevalence continues to grow and there remains a significant diagnostic gap in one-third of the US population that has pre-diabetes. Innovative, practical strategies to improve monitoring of glycemic health are desperately needed. In this proof-of-concept study, we explore the relationship between non-invasive wearables and glycemic metrics and demonstrate the feasibility of using non-invasive wearables to estimate glycemic metrics, including hemoglobin A1c (HbA1c) and glucose variability metrics. RESEARCH DESIGN AND METHODS: We recorded over 25 000 measurements from a continuous glucose monitor (CGM) with simultaneous wrist-worn wearable (skin temperature, electrodermal activity, heart rate, and accelerometry sensors) data over 8-10 days in 16 participants with normal glycemic state and pre-diabetes (HbA1c 5.2-6.4). We used data from the wearable to develop machine learning models to predict HbA1c recorded on day 0 and glucose variability calculated from the CGM. We tested the accuracy of the HbA1c model on a retrospective, external validation cohort of 10 additional participants and compared results against CGM-based HbA1c estimation models. RESULTS: A total of 250 days of data from 26 participants were collected. Out of the 27 models of glucose variability metrics that we developed using non-invasive wearables, 11 of the models achieved high accuracy (<10% mean average per cent error, MAPE). Our HbA1c estimation model using non-invasive wearables data achieved MAPE of 5.1% on an external validation cohort. The ranking of wearable sensor's importance in estimating HbA1c was skin temperature (33%), electrodermal activity (28%), accelerometry (25%), and heart rate (14%). CONCLUSIONS: This study demonstrates the feasibility of using non-invasive wearables to estimate glucose variability metrics and HbA1c for glycemic monitoring and investigates the relationship between non-invasive wearables and the glycemic metrics of glucose variability and HbA1c. The methods used in this study can be used to inform future studies confirming the results of this proof-of-concept study.

Cough hypersensitivity and suppression in COPD.

Cough reflex hypersensitivity and impaired cough suppression are features of chronic refractory cough (CRC). Little is known about cough suppression and cough reflex hypersensitivity in cough associated with chronic obstructive pulmonary disease (COPD). This study investigated the ability of patients with COPD to suppress cough during a cough challenge test in comparison to patients with CRC and healthy subjects. This study also investigated whether cough reflex hypersensitivity is associated with chronic cough in COPD.Participants with COPD (n=27) and CRC (n=11) and healthy subjects (n=13) underwent capsaicin challenge tests with and without attempts to self-suppress cough in a randomised order over two visits, 5 days apart. For patients with COPD, the presence of self-reported chronic cough was documented, and objective 24-h cough frequency was measured.Amongst patients with COPD, those with chronic cough (n=16) demonstrated heightened cough reflex sensitivity compared to those without chronic cough (n=11): geometric mean±sd capsaicin dose thresholds for five coughs (C5) 3.36±6.88 µmol·L-1 versus 44.50±5.90 µmol·L-1, respectively (p=0.003). Participants with CRC also had heightened cough reflex sensitivity compared to healthy participants: geometric mean±sd C5 3.86±5.13 µmol·L-1 versus 45.89±3.95 µmol·L-1, respectively (p<0.001). Participants with COPD were able to suppress capsaicin-evoked cough, regardless of the presence or absence of chronic cough: geometric mean±sd capsaicin dose thresholds for 5 coughs without self-suppression attempts (C5) and with (CS5) were 3.36±6.88 µmol·L-1 versus 12.80±8.33 µmol·L-1 (p<0.001) and 44.50±5.90 µmol·L-1 versus 183.2±6.37 µmol·L-1 (p=0.006), respectively. This was also the case for healthy participants (C5 versus CS5: 45.89±3.95 µmol·L-1 versus 254.40±3.78 µmol·L-1, p=0.033), but not those with CRC, who were unable to suppress capsaicin-evoked cough (C5 versus CS5: 3.86±5.13 µmol·L-1 versus 3.34±5.04 µmol·L-1, p=0.922). C5 and CS5 were associated with objective 24-h cough frequency in patients with COPD: ρ= -0.430, p=0.036 and ρ= -0.420, p=0.041, respectively.Patients with COPD-chronic cough and CRC both had heightened cough reflex sensitivity but only patients with CRC were unable to suppress capsaicin-evoked cough. This suggests differing mechanisms of cough between patients with COPD and CRC, and the need for disease-specific approaches to its management.

Perioperative analgesia associated with oral administration of a novel methadone-fluconazole-naltrexone formulation in dogs undergoing routine ovariohysterectomy.

OBJECTIVE: To determine perioperative analgesia associated with oral administration of a novel methadone-fluconazole-naltrexone formulation in dogs undergoing routine ovariohysterectomy. ANIMALS: 43 healthy female dogs. PROCEDURES: Dogs were randomly assigned to receive the methadone-fluconazole-naltrexone formulation at 1 of 2 dosages (0.5 mg/kg, 2.5 mg/kg, and 0.125 mg/kg, respectively, or 1.0 mg/kg, 5.0 mg/kg, and 0.25 mg/kg, respectively, PO, q 12 h, starting the evening before surgery; n = 15 each) or methadone alone (0.5 mg/kg, SC, q 4 h starting the morning of surgery; 13). Dogs were sedated with acepromazine, and anesthesia was induced with propofol and maintained with isoflurane. A standard ovariohysterectomy was performed by experienced surgeons. Sedation and pain severity (determined with the Glasgow Composite Pain Scale-short form [GCPS-SF]) were scored for 48 hours after surgery. Rescue analgesia was to be provided if the GCPS-SF score was > 6. Dogs also received carprofen starting the day after surgery. RESULTS: None of the dogs required rescue analgesia. The highest recorded GCPS-SF score was 4. A significant difference in GCPS-SF score among groups was identified at 6:30 am the day after surgery, but not at any other time. The most common adverse effect was perioperative vomiting, which occurred in 11 of the 43 dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Oral administration of a methadone-fluconazole-naltrexone formulation at either of 2 dosages every 12 hours (3 total doses) was as effective as SC administration of methadone alone every 4 hours (4 total doses) in dogs undergoing routine ovariohysterectomy. Incorporation of naltrexone in the novel formulation may provide a deterrent to human opioid abuse or misuse.

Effect of continuous positive airway pressure on maximal exercise capacity in patients with obstructive sleep apnea: a systematic review and meta-analysis.

STUDY OBJECTIVES: Exercise capacity is impaired in obstructive sleep apnea (OSA). There are conflicting reports on the effect of continuous positive airway pressure (CPAP) on maximal exercise capacity. The objective of this review was to determine if there is a change in exercise capacity and anaerobic threshold following CPAP treatment in OSA patients. METHODS: We conducted a systematic review and meta-analyses to summarize the changes in peak rate of oxygen uptake (V̇O2 peak) or maximum rate of oxygen uptake (V̇O2 max) and anaerobic threshold (AT) during cardiopulmonary exercise testing following CPAP intervention in patients with OSA. A systematic literature review was conducted to identify published literature on markers of V̇O2 peak, V̇O2 max, and AT pre- vs post-CPAP using a web-based literature search of PubMed/MEDLINE, Embase, CINAHL, and Cochrane review (CENTRAL) databases. Two independent reviewers screened the articles for data extraction and analysis. RESULTS: The total search of all the databases returned 470 relevant citations. Following application of eligibility criteria, 6 studies were included in the final meta-analysis for V̇O2 peak, 2 studies for V̇O2 max, and five studies for AT. The meta-analysis showed a mean net difference in V̇O2 peak between pre- and post-CPAP of 2.69 mL·kg-1·min-1, P = .02, favoring treatment with CPAP. There was no difference in V̇O2 max or AT with CPAP treatment (mean net difference 0.66 mL·kg-1·min-1 [P = .78] and -144.98 mL·min-1 [P = .20] respectively). CONCLUSIONS: There is a paucity of high-quality studies investigating the effect of CPAP on exercise capacity. Our meta-analysis shows that V̇O2 peak increases following CPAP treatment in patients with OSA, but we did not observe any change in V̇O2 max or AT. Our findings should be considered preliminary and we recommend further randomized controlled trials to confirm our findings and to clarify the peak and maximum rates of oxygen uptake adaptations with CPAP therapy.