Aging in females is associated with changes in respiratory modulation of sympathetic nerve activity and blood pressure.

Sympathetic nerve activity (SNA) is tightly coupled with the respiratory cycle. In healthy human males, respiratory modulation of SNA does not change with age. However, it is unclear how this modulation is affected by age in females. We investigated whether respiratory sympathetic modulation is altered in healthy postmenopausal (PMF) versus premenopausal female (YF), and younger male (YM) adults, and determined its relationship to resting blood pressure. Muscle SNA (MSNA; microneurography), respiration (transducer belt), ECG, and continuous blood pressure were measured in 12 YF, 13 PMF, and 12 YM healthy volunteers. Respiratory modulation of MSNA was quantified during two phases of the respiratory cycle: mid-late expiration and inspiration/postinspiration. All groups showed respiratory modulation of MSNA (P < 0.0005). There was an interaction between the respiratory phase and group for MSNA [bursts/100 heartbeats (HB) (P = 0.004) and bursts/min (P = 0.029)], with smaller reductions in MSNA during inspiration observed in PMF versus the other groups. Respiratory modulation of blood pressure was also reduced in PMF versus YF (6 [2] vs. 12 [9] mmHg, P = 0.008) and YM (13 [13] mmHg, P = 0.001, median [interquartile range]). The magnitude of respiratory sympathetic modulation was related to resting blood pressure in PMF only, such that individuals with less modulation had greater resting blood pressure. The data indicate that aging in postmenopausal females is associated with less inspiratory inhibition of MSNA. This correlated with a higher resting blood pressure in PMF only. Thus, the reduced modulation of MSNA could contribute to the age-related rise in blood pressure that occurs in females.NEW & NOTEWORTHY The current study demonstrates that respiratory modulation of sympathetic nerve activity (SNA) is reduced in healthy postmenopausal (PMF) versus premenopausal females (YF). Furthermore, respiratory sympathetic modulation was negatively related to resting blood pressure in postmenopausal females, such that blood pressure was greater in individual with less modulation. Reduced respiratory sympathetic modulation may have implications for the autonomic control of blood pressure in aging postmenopausal females, by contributing to age-related sympathetic activation and reducing acute, respiratory-linked blood pressure variation.

COVID-19-related changes in outpatient CPAP setup pathways for OSA are linked with decreased 30-day CPAP usage.

The COVID-19 pandemic changed continuous positive airway pressure (CPAP) setup pathways. We evaluated patients commenced on CPAP in 2019 (prepandemic) and 2020 (post-first UK wave). Face-to-face (F2F) setup numbers, with CPAP turned on, decreased from 613 patients (98.9%) in 2019, to 6 (1.1%) in 2020. In 2020, setups were F2F without CPAP turned on (403 (71.1%)), or remote (158 (27.9%)). Prepandemic median CPAP usage at first follow-up was 5.4 (2.7-6.9) hours/night and fell by 0.9 hours/night (95% CI 0.5 to 1.2, p<0.0001) in 2020. We found clinically relevant reductions in CPAP usage with pathway changes post-COVID-19.

Comparing enhanced versus standard Diabetes Prevention Program among indigenous adults in an urban setting: a randomized controlled trial.

BACKGROUND: Indigenous people in the United States are at high risk for diabetes. Psychosocial stressors like historical trauma may impede success in diabetes prevention programs. METHODS: A comparative effectiveness trial compared a culturally tailored diabetes prevention program (standard group) with an enhanced one that addressed psychosocial stressors (enhanced group) in 2015 to 2017. Participants were 207 Indigenous adults with a body mass index (BMI) of ≥30 and one additional criterion of metabolic syndrome, and were randomized to the standard or enhanced group. Both groups received a culturally tailored behavioral diabetes prevention program. Strategies to address psychosocial stressors were provided to the enhanced group only. Change in BMI over 12 months was the primary outcome. Secondary outcomes included change in quality of life, and clinical, behavioral, and psychosocial measures at 6 and 12 months. RESULTS: The two groups did not significantly differ in BMI change at 12 months. The two groups also did not differ in any secondary outcomes at 6 or 12 months, with the exception of unhealthy food consumption; the standard group reported a larger mean decrease (95% CI) in consumption of unhealthy food compared with the enhanced group (- 4.6 [- 6.8, - 2.5] vs. -0.7 [- 2.9, 1.4], p = 0.01). At 6 months, significant improvements in weight and the physical component of the quality of life measure were observed for both groups compared with their baseline level. Compared with baseline, at 12 months, the standard group showed significant improvement in BMI (mean [95% CI], - 0.5 [- 1.0, - 0.1]) and the enhanced group showed significant improvement in the physical component of the quality of life (2.9 [0.7, 5.2]). CONCLUSIONS: Adding strategies to address psychosocial barriers to a culturally tailored diabetes prevention program was not successful for improving weight loss among urban Indigenous adults. TRIAL REGISTRATION: (if applicable): NCT02266576. Registered October 17, 2014 on clinicaltrials.gov. The trial was prospectively registered.

Executive Summary: 2017 ERS/ATS standards for single-breath carbon monoxide uptake in the lung.

This document summarises an update to the European Respiratory Society (ERS)/American Thoracic Society (ATS) technical standards for single-breath carbon monoxide uptake in the lung that was last updated in 2005. The full standards are also available online as https://doi.org/10.1183/13993003.00016-2016 The major changes in these technical standards relate to DLCO measurement with systems using rapidly responding gas analysers for carbon monoxide and the tracer gas, which are now the most common type of DLCO instrumentation being manufactured. Technical improvements and the increased capability afforded by these new systems permit enhanced measurement of DLCO and the opportunity to include other optional measures of lung function.

2017 ERS/ATS standards for single-breath carbon monoxide uptake in the lung.

This document provides an update to the European Respiratory Society (ERS)/American Thoracic Society (ATS) technical standards for single-breath carbon monoxide uptake in the lung that was last updated in 2005. Although both DLCO (diffusing capacity) and TLCO (transfer factor) are valid terms to describe the uptake of carbon monoxide in the lung, the term DLCO is used in this document. A joint taskforce appointed by the ERS and ATS reviewed the recent literature on the measurement of DLCO and surveyed the current technical capabilities of instrumentation being manufactured around the world. The recommendations in this document represent the consensus of the taskforce members in regard to the evidence available for various aspects of DLCO measurement. Furthermore, it reflects the expert opinion of the taskforce members on areas in which peer-reviewed evidence was either not available or was incomplete. The major changes in these technical standards relate to DLCO measurement with systems using rapidly responding gas analysers for carbon monoxide and the tracer gas, which are now the most common type of DLCO instrumentation being manufactured. Technical improvements and the increased capability afforded by these new systems permit enhanced measurement of DLCO and the opportunity to include other optional measures of lung function.

A systematic review on adherence to continuous positive airway pressure (CPAP) treatment for obstructive sleep apnoea (OSA) in individuals with mild cognitive impairment and Alzheimer's disease dementia.

Obstructive sleep apnoea (OSA) is highly prevalent in mild cognitive impairment (MCI) and Alzheimer's disease (AD). The gold standard treatment for OSA is continuous positive airway pressure (CPAP). Long-term, well-powered efficacy trials are required to understand whether CPAP could slow cognitive decline in individuals with MCI/AD, but its tolerability in this group remains uncertain. The present review investigates CPAP adherence among individuals with OSA and MCI/AD. Electronic searches were performed on 8 databases. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Six independent studies and four secondary analyses included 278 unique participants (mean age = 72.1 years). In five of the retained studies, around half of participants (45% N = 85 MCI, 56% N = 22 AD) were adherent to CPAP, where ≥4 h use per night was considered adherent. Three of the retained studies also reported average CPAP use to range between 3.2 and 6.3 h/night. CPAP adherence in individuals with MCI and AD is low, albeit similar to the general elderly population. Reporting adherence in future studies as both average duration as well as using a binary cut-off would improve our understanding of the optimum CPAP use in dementia clinical trials and care.

Carotid body dysregulation contributes to Long COVID symptoms.

BACKGROUND: The symptoms of long COVID, which include fatigue, breathlessness, dysregulated breathing, and exercise intolerance, have unknown mechanisms. These symptoms are also observed in heart failure and are partially driven by increased sensitivity of the carotid chemoreflex. As the carotid body has an abundance of ACE2 (the cell entry mechanism for SARS-CoV-2), we investigated whether carotid chemoreflex sensitivity was elevated in participants with long COVID. METHODS: Non-hositalised participants with long-COVID (n = 14) and controls (n = 14) completed hypoxic ventilatory response (HVR; the measure of carotid chemoreflex sensitivity) and cardiopulmonary exercise tests. Parametric and normally distributed data were compared using Student's unpaired t-tests or ANOVA. Nonparametric equivalents were used where relevant. Peason's correlation coefficient was used to examine relationships between variables. RESULTS: During cardiopulmonary exercise testing the VE/VCO2 slope (a measure of breathing efficiency) was higher in the long COVID group (37.8 ± 4.4) compared to controls (27.7 ± 4.8, P = 0.0003), indicating excessive hyperventilation. The HVR was increased in long COVID participants (-0.44 ± 0.23 l/min/ SpO2%, R2 = 0.77 ± 0.20) compared to controls (-0.17 ± 0.13 l/min/SpO2%, R2 = 0.54 ± 0.38, P = 0.0007). The HVR correlated with the VE/VCO2 slope (r = -0.53, P = 0.0036), suggesting that excessive hyperventilation may be related to carotid body hypersensitivity. CONCLUSIONS: The carotid chemoreflex is sensitised in long COVID and may explain dysregulated breathing and exercise intolerance in these participants. Tempering carotid body excitability may be a viable treatment option for long COVID patients.

Patients with long COVID suffer from breathlessness during exercise, leading to exercise intolerance. We know that SARS-CoV-2, the virus that causes COVID-19, can infect carotid bodies which is a small sensory organ that sends signals to the brain for regulating breathing and blood pressure. This is called the carotid chemoreflex. However, it is not clear if SARS-CoV-2 infection affects carotid chemoreflex. Here, we examine whether the normal functioning of carotid chemoreflex is disrupted in non-hospitalised patients with long COVID and if this is linked to excessive breathing during exercise. Our study shows that carotid chemoreflex is more sensitive in long COVID patients, who are otherwise healthy. The carotid bodies could be a good therapeutic target for treating breathlessness in patients with long COVID.

Ventilatory Efficiency Is Reduced in People With Hypertension During Exercise.

Background An elevated ventilatory efficiency slope during exercise (minute ventilation/volume of expired CO2; VE/VCO2 slope) is a strong prognostic indicator in heart failure. It is elevated in people with heart failure with preserved ejection, many of whom have hypertension. However, whether the VE/VCO2 slope is also elevated in people with primary hypertension versus normotensive individuals is unknown. We hypothesize that there is a spectrum of ventilatory inefficiency in cardiovascular disease, reflecting an increasingly abnormal physiological response to exercise. The aim of this study was to evaluate the VE/VCO2 slope in patients with hypertension compared with age-, peak oxygen consumption-, and sex-matched healthy subjects. Methods and Results Ramped cardiovascular pulmonary exercise tests to peak oxygen consumption were completed on a bike ergometer in 55 patients with primary hypertension and 24 normotensive controls. The VE/VCO2 slope was assessed from the onset of exercise to peak oxygen consumption. Data were compared using unpaired Student t test. Age (mean±SD, 66±6 versus 64±6 years; P=0.18), body mass index (25.4±3.5 versus 24±2.4 kg/m2; P=0.13), and peak oxygen consumption (23.2±6.6 versus 24±7.3 mL/min per kg; P=0.64) were similar between groups. The VE/VCO2 slope was elevated in the hypertensive group versus controls (31.8±4.5 versus 28.4±3.4; P=0.002). Only 27% of the hypertensive group were classified as having a normal VE/VCO2 slope (20-30) versus 71% in the control group. Conclusions Ventilatory efficiency is impaired people with hypertension without a diagnosis of heart failure versus normotensive individuals. Future research needs to establish whether those patients with hypertension with elevated VE/VCO2 slopes are at risk of developing future heart failure.

Correlation between perceived asthma control and thoraco-abdominal asynchrony in primary care patients diagnosed with asthma.

OBJECTIVE: Thoraco-abdominal asynchrony (TAA), the discordant movement of the abdomen and thorax, may impact upon health-related variables. Here, we investigated the extent to which TAA is associated with health-related variables, particularly perceived asthma control and quality of life. METHODS: Ambulatory respiratory data from 43 patients diagnosed with asthma and 43 healthy age and sex-matched controls were recorded over 4 hours. Phase relation (Ph Rel Total), the percentage of time that the effects of rib cage (RC) and diaphragmatic movement result in opposite effects on intra-thoracic volume, quantified TAA. Subjects completed the Mini Asthma Quality of Life Questionnaire (AQLQ), Asthma Control Questionnaire (ACQ), Nijmegen questionnaire (NQ), Hospital Anxiety and Depression Scale (HADS), Spielberger State-Trait Anxiety Inventory (STAI), and General Health Perception (GHP) subscale of the short form 36 questionnaire'. Capnography profiling, breath-hold time (BHT), and standard spirometry were performed. RESULTS: The time in asynchrony was significantly greater in the asthma than in the healthy control group (Ph Rel Total = 14% (interquartile range (IQR) 8.5-20.7%) versus 10.4% (IQR 7.1-14.5%), p = .012). In patients with asthma, Ph Rel Total was weakly associated with poorer ACQ scores (r = 0.33, p = .03), and in the healthy control group with GHP (r = 0.319, p = .037). Post-hoc exploratory analysis revealed a moderate relationship in the female asthma subgroup between Ph Rel Total and AQLQ (r = -0.56, p = .003). CONCLUSIONS: TAA may be associated with decreased perceived asthma control. In healthy individuals, asynchrony may be associated with low perception of general health. Further studies are required to investigate if the reduction of TAA improves these health-related variables.

International consensus on lung function testing during the COVID-19 pandemic and beyond.

Coronavirus disease 2019 (COVID-19) has negatively affected the delivery of respiratory diagnostic services across the world due to the potential risk of disease transmission during lung function testing. Community prevalence, reoccurrence of COVID-19 surges and the emergence of different variants of SARS-CoV-2 have impeded attempts to restore services. Finding consensus on how to deliver safe lung function services for both patients attending and for staff performing the tests are of paramount importance. This international statement presents the consensus opinion of 23 experts in the field of lung function and respiratory physiology balanced with evidence from the reviewed literature. It describes a robust roadmap for restoration and continuity of lung function testing services during the COVID-19 pandemic and beyond. Important strategies presented in this consensus statement relate to the patient journey when attending for lung function tests. We discuss appointment preparation, operational and environmental issues, testing room requirements including mitigation strategies for transmission risk, requirement for improved ventilation, maintaining physical distance and use of personal protection equipment. We also provide consensus opinion on precautions relating to specific tests, filters, management of special patient groups and alternative options to testing in hospitals. The pandemic has highlighted how vulnerable lung function services are and forces us to re-think how long-term mitigation strategies can protect our services during this and any possible future pandemic. This statement aspires to address the safety concerns that exist and provide strategies to make lung function tests and the testing environment safer when tests are required.

ARTP statement on pulmonary function testing 2020.

The Association for Respiratory Technology & Physiology (ARTP) last produced a statement on the performance of lung function testing in 1994. At that time the focus was on a practical statement for people working in lung function laboratories. Since that time there have been many technological advances and alterations to best practice in the measurement and interpretation of lung function assessments. In light of these advances an update was warranted. ARTP, therefore, have provided within this document, where available, the most up-to-date and evidence-based recommendations for the most common lung function assessments performed in laboratories across the UK. These recommendations set out the requirements and considerations that need to be made in terms of environmental and patient factors that may influence both the performance and interpretation of lung function tests. They also incorporate procedures to ensure quality assured diagnostic investigations that include those associated with equipment, the healthcare professional conducting the assessments and the results achieved by the subject. Each section aims to outline the common parameters provided for each investigation, a brief principle behind the measurements (where applicable), and suggested acceptability and reproducibility criteria.

A validation of the 7.5% CO2 model of GAD using paroxetine and lorazepam in healthy volunteers.

The inhalation of 7.5% carbon dioxide (CO2) in healthy subjects produces an increase in blood pressure and heart rate, and increased feelings of anxiety, fear and tension (Bailey et al. 2005). As this state is similar to that of general anxiety rather than panic, we further validated this by examining the effects of anxiolytic medication. Two separate studies in healthy volunteers are described; study one is a double-blind, placebo-controlled study of a single dose of 2 mg lorazepam and study two describes the effects of 21 days of treatment with paroxetine. Gas challenges were air and 7.5% CO2 inhaled for 20 minutes, delivered on day 0 (before treatment) and day 21 (after treatment) in the paroxetine study. Subjective effects were measured using visual analogue scales and questionnaires. When compared with placebo, lorazepam 2 mg significantly reduced peak CO2-induced subjective fear, feelings of wanting to leave, tension and worry. In the paroxetine study, when compared with day 0, day 21 showed a significantly attenuated peak CO2-induced nervousness and a trend for reduced ratings of anxiety, fear, feel like leaving, tense and worried. In these studies we have shown that this CO2 model of anxiety is sensitive to lorazepam and to a lesser extent paroxetine. This gives support to its utility as an experimental model of general anxiety disorder in healthy volunteers.

Inhalation of 35% CO(2) results in activation of the HPA axis in healthy volunteers.

BACKGROUND: The hypothalamo-pituitary-adrenal (HPA) axis is a major stress responsive system in humans. Although there are numerous ways of testing responsiveness of the HPA in experimental animals, this is much more difficult in man. Hypercapnea is a very stressful stimulus for humans and has been used as an anxiogenic probe in psychiatric patients. We have now investigated whether the simple challenge of a single 35% inhalation of CO(2) activates the neuroendocrine system as evidenced by changes in HPA activity, as well as cardiovascular and subjective responses, in healthy volunteers. METHODS: Fourteen healthy male volunteers were recruited. They underwent single vital capacity inhalation of room air and 35% CO(2), in a single blind fashion. Neuroendocrine, cardiovascular and subjective fear measures were taken at regular intervals. RESULTS: CO(2) inhalation produced significant activation of the HPA axis in all subjects, as measured with plasma cortisol. Heart rate was decreased and systolic blood pressure was significantly increased shortly after the inhalation of CO(2). The subjects reported short-lived symptoms of fear with the experimental gas. CONCLUSIONS: Single vital capacity inhalation of 35% CO(2) activated the HPA axis in healthy volunteers. It also had a significant cardiovascular and psychological (anxiogenic) effect, as expected from previous published studies. The test is potentially useful in studying the responsivity of the HPA axis in health and disease.

Central hypoventilation with PHOX2B expansion mutation presenting in adulthood.

The case history is described of a 41 year old male who presented with acute-on-chronic respiratory failure due to PHOX2B mutation-associated central hypoventilation with a quantified impaired response to hypercapnia. He was successfully treated with non-invasive ventilation, which has been continued nocturnally at home.

Sleep-wake disturbances in patients with advanced cancer and their family carers.

Sleep disturbance is common in patients with advanced cancer, and their family carers also may suffer from sleep problems. The aims of this study were to determine the prevalence of sleep-wake disturbances in patients with advanced cancer and their carers, to monitor the amount of daytime spent in activity and rest, and to examine the relationship between sleep, physical, and psychological symptoms. This was a prospective, descriptive observational study in patients with advanced incurable cancer and their carers attending a regional cancer center, using subjective (Short Form-36, Epworth Sleepiness Score, Hospital Anxiety and Depression Scale, Memorial Symptom Assessment Scale, and sleep history and diary) and objective (Actiwatch) assessments over a seven-day period. Sixty patients with advanced cancer and their family carers completed the study. Poor sleep was a frequent complaint: 47% of the patients and 42% of the carers reported that they did not sleep well, yet patients reported sleeping an average of 8.2 hours and carers 7.8 hours per night. The objective assessments revealed that although sleep efficiency (SE) was greater than 90% for most patients and carers, sleep fragmentation was high in both groups. Patients and carers who complained of poor sleep were significantly more anxious (P<0.001 and <0.05) compared with patients and carers who reported sleeping well. Patients who complained of poor sleep had significantly more pain (P<0.05). These results show that a substantial proportion of advanced cancer patients and their carers complained of poor sleep despite reporting "normal" duration of sleep. Objective measurements using Actiwatch revealed good SE but high levels of sleep fragmentation and movement, suggesting that sleep quality may be disturbed. Further work is required to investigate sleep quality and the consequences of poor sleep. In the meantime, health care professionals need to routinely inquire about sleep and consider possible reversible underlying factors, such as pain and anxiety, for those who report sleep disturbance.

Behavioral and cardiovascular effects of 7.5% CO2 in human volunteers.

The study of carbon dioxide (CO2) inhalation in psychiatry has a long and varied history, with recent interest in using inhaled CO2 as an experimental tool to explore the neurobiology and treatment of panic disorder. As a consequence, many studies have examined the panic-like response to the gas either using the single or double breath 35% CO2 inhalation or 5-7% CO2 inhaled for 15-20 min, or rebreathing 5% CO2 for a shorter time. However, this lower dose regime produces little physiological or psychological effects in normal volunteers. For this reason we have studied the effects of a higher concentration of CO2, 7.5%, given over 20 min. Twenty healthy volunteers were recruited to a double blind, placebo-controlled study where air and 7.5% CO2 were inhaled for 20 min. Cardiovascular measures and subjective ratings were obtained. When compared to air, inhaling 7.5% CO2 for 20 min increases systolic blood pressure and heart rate, indicating increased autonomic arousal. It also increases ratings of anxiety and fear and other subjective symptoms associated with an anxiety state. The inhalation of 7.5% CO2 for 20 min is safe for use in healthy volunteers and produces robust subjective and objective effects. It seems promising as an anxiety provocation test that could be beneficial in the study of the effects of anxiety on sustained performance, the discovery of novel anxiolytic agents, and the study of brain circuits and mechanisms of anxiety.