The impact of obstructive sleep apnea treatment on microvascular complications in patients with type 2 diabetes: a feasibility randomized controlled trial.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is associated with an increased risk of diabetes-related complications. Hence, it is plausible that Continuous Positive Airway Pressure (CPAP) could have a favorable impact on these complications. To assess the feasibility of conducting a randomized control trial (RCT) in patients with type 2 diabetes (T2D) and OSA over 2 years. METHODS: An open-label multicenter feasibility RCT of CPAP vs no CPAP in patients with T2D and OSA. Patients with resting oxygen saturation <90%, central apnea index >15/hour or Epworth Sleepiness Scale (ESS) ≥11 were excluded. OSA was diagnosed using a multichannel portable device (ApneaLink Air, ResMed). The primary outcome measures were related to feasibility, and the secondary outcomes were changes in various clinical and biochemical parameters related to diabetes outcomes. RESULTS: Eighty-three (40 CPAP vs 43 no CPAP) patients were randomized, with a median (IQR) follow-up of 645 [545, 861] days. CPAP compliance was inadequate, with a median usage of approximately 3.5 hours/night. Early CPAP use predicted longer-term compliance. The adjusted analysis showed a possible favorable association between being randomized to CPAP and several diabetes-related endpoints (chronic kidney disease (CKD), neuropathy, and quality of life (QoL)). CONCLUSIONS: It was feasible to recruit, randomize, and achieve a high follow-up rate over 2 years in patients with OSA and T2D. CPAP compliance might improve by a run-in period before randomization. A full RCT is necessary to assess the observed favorable association between CPAP and CKD, neuropathy, and QoL in patients with T2D. CLINICAL TRIAL REGISTRATION: Registry: ISRCTN; URL: https://www.isrctn.com/ISRCTN12361838; Title: The impact of sleep disorders in patients with type 2 diabetes; Identifier: ISRCTN12361838.

Engaging stakeholders to level up COPD care in LMICs: lessons learned from the "Breathe Well" programme in Brazil, China, Georgia, and North Macedonia.

BACKGROUND: Effective stakeholder engagement in health research is increasingly being recognised and promoted as an important pathway to closing the gap between knowledge production and its use in health systems. However, little is known about its process and impacts, particularly in low-and middle-income countries. This opinion piece draws on the stakeholder engagement experiences from a global health research programme on Chronic Obstructive Pulmonary Disease (COPD) led by clinician researchers in Brazil, China, Georgia and North Macedonia, and presents the process, outcomes and lessons learned. MAIN BODY: Each country team was supported with an overarching engagement protocol and mentored to develop a tailored plan. Patient involvement in research was previously limited in all countries, requiring intensive efforts through personal communication, meetings, advisory groups and social media. Accredited training programmes were effective incentives for participation from healthcare providers; and aligning research findings with competing policy priorities enabled interest and dialogue with decision-makers. The COVID-19 pandemic severely limited possibilities for planned engagement, although remote methods were used where possible. Planned and persistent engagement contributed to shared knowledge and commitment to change, including raised patient and public awareness about COPD, improved skills and practice of healthcare providers, increased interest and support from clinical leaders, and dialogue for integrating COPD services into national policy and practice. CONCLUSION: Stakeholder engagement enabled relevant local actors to produce and utilise knowledge for small wins such as improving day-to-day practice and for long-term goals of equitable access to COPD care. For it to be successful and sustained, stakeholder engagement needs to be valued and integrated throughout the research and knowledge generation process, complete with dedicated resources, contextualised and flexible planning, and commitment.

Randomised controlled trial testing effectiveness of feedback about lung age or exhaled CO combined with very brief advice for smoking cessation compared to very brief advice alone in North Macedonia: findings from the Breathe Well group.

INTRODUCTION: In 2019, smoking prevalence in North Macedonia was one of the world's highest at around 46% in adults. However, access to smoking cessation treatment is limited and no co-ordinated smoking cessation programmes are provided in primary care. METHODS: We conducted a three parallel-armed randomised controlled trial (n = 1368) to investigate effectiveness and cost-effectiveness of lung age (LA) or exhaled carbon monoxide (CO) feedback combined with very brief advice (VBA) to prompt smoking cessation compared with VBA alone, delivered by GPs in primary care in North Macedonia. All participants who decided to attempt to quit smoking were advised about accessing smoking cessation medications and were also offered behavioural support as part of the "ACT" component of VBA. Participants were aged ≥ 35 years, smoked ≥ 10 cigarettes per day, were recruited from 31 GP practices regardless of motivation to quit and were randomised (1:1:1) using a sequence generated before the start of recruitment. The primary outcome was biochemically validated 7-day point prevalence abstinence at 4 weeks (wks). Participants and GPs were not blinded to allocation after randomisation, however outcome assessors were blind to treatment allocation. RESULTS: There was no evidence of a difference in biochemically confirmed quitting between intervention and control at 4wks (VBA + LA RR 0.90 (97.5%CI: 0.35, 2.27); VBA + CO RR 1.04 (97.5%CI: 0.44, 2.44)), however the absolute number of quitters was small (VBA + LA 1.6%, VBA + CO 1.8%, VBA 1.8%). A similar lack of effect was observed at 12 and 26wks, apart from in the VBA + LA arm where the point estimate was significant but the confidence intervals were very wide. In both treatment arms, a larger proportion reported a reduction in cigarettes smoked per day at 4wks (VBA + LA 1.30 (1.10, 1.54); VBA + CO 1.23 (1.03, 1.49)) compared with VBA. The point estimates indicated a similar direction of effect at 12wks and 26wks, but differences were not statistically significant. Quantitative process measures indicated high fidelity to the intervention delivery protocols, but low uptake of behavioural and pharmacological support. VBA was the dominant intervention in the health economic analyses. CONCLUSION: Overall, there was no evidence that adding LA or CO to VBA increased quit rates. However, a small effect cannot be ruled out as the proportion quitting was low and therefore estimates were imprecise. There was some evidence that participants in the intervention arms were more likely to reduce the amount smoked, at least in the short term. More research is needed to find effective ways to support quitting in settings like North Macedonia where a strong smoking culture persists. TRIAL REGISTRATION: The trial was registered at http://www.isrctn.com (ISRCTN54228638) on the 07/09/2018.

European Respiratory Society/American Thoracic Society technical statement: standardisation of the measurement of lung volumes, 2023 update.

This document updates the 2005 European Respiratory Society (ERS) and American Thoracic Society (ATS) technical standard for the measurement of lung volumes. The 2005 document integrated the recommendations of an ATS/ERS task force with those from an earlier National Heart, Lung, and Blood Institute workshop that led to the publication of background papers between 1995 and 1999 and a consensus workshop report with more in-depth descriptions and discussion. Advancements in hardware and software, new research and emerging approaches have necessitated an update to the 2005 technical standard to guide laboratory directors, physiologists, operators, pulmonologists and manufacturers. Key updates include standardisation of linked spirometry, new equipment quality control and validation recommendations, generalisation of the multiple breath washout concept beyond nitrogen, a new acceptability and grading system with addition of example tracings, and a brief review of imaging and other new techniques to measure lung volumes. Future directions and key research questions are also noted.

Community lung health service design for COPD patients in China by the Breathe Well group.

COPD is increasingly common in China but is poorly understood by patients, medications are not used as prescribed and there is no access to recommended non-pharmacological treatment. We explored COPD patients' and general practitioners' (GPs) knowledge of COPD, views on its management and the acceptability of a flexible lung health service (LHS) offering health education, exercise, self-management, smoking cessation and mental health support. Using a convergent mixed methods design, data were collected from patients and GPs using focus groups (FGs) in four Chinese cities, questionnaires were also used to collect data from patients. FGs were audio-recorded and transcribed. Quantitative data were analysed descriptively, thematic framework analysis was used for the qualitative data. Two-hundred fifty-one patients completed the questionnaire; 39 patients and 30 GPs participated in ten separate FGs. Three overarching themes were identified: patients' lack of knowledge/understanding of COPD, current management of COPD not meeting patients' needs and LHS design, which was well received by patients and GPs. Participants wanted COPD education, TaiChi, psychological support and WeChat for social support. 39% of survey responders did not know what to do when their breathing worsened and 24% did not know how to use their inhalers. 36% of survey respondents requested guided relaxation. Overall, participants did not fully understand the implications of COPD and current treatment was sub-optimal. There was support for developing a culturally appropriate intervention meeting Chinese patients' needs, health beliefs, and local healthcare delivery. Further research should explore the feasibility of such a service.

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.

The benefits of a home non-invasive ventilation retrieval service: Improved effectiveness and environmental sustainability in challenging times.

In the last 6 months, home non-invasive ventilation (NIV) services have faced several unanticipated challenges to their effectiveness and delivery as the result of a 'perfect storm' of the COVID-19 pandemic demands. We developed and delivered an innovative follow-up service, to support home NIV delivery, and improve cost-effectiveness and sustainability during COVID-19. Between Feb-2019 and Nov-2020, 92 post-acute patients were issued with home NIV; 25 (27%) out of the 92 patients had unused NIV machines successfully retrieved. The median (IQR) days of home NIV usage were 207 (98) for patients who had their machines returned. All the unused NIV machines retrieved were within the 5-year working life guaranteed by the manufacturer and were all redeployed after appropriate reconditioning and infection control measures. Without the home-visiting and recycling pilot, we would have relied on patients and families to return the unused machines. Given the expected disruption to NIV machine supply for at least the foreseeable 12-18 months, we feel it is important to get this important message out to other home NIV services urgently. Wider implementation of this novel approach could increase the availability of this vital resource and help meet the current demand on home NIV services.

Effect of obstructive sleep apnoea on retinal microvascular function: a randomised controlled trial.

PURPOSE: Retinal microvascular endothelial dysfunction is thought to be of importance in the development of ocular vascular diseases. Obstructive sleep apnoea (OSA) causes macrovascular endothelial dysfunction, but the effect of OSA on retinal microvascular endothelial function is not known. We aimed to determine the effect of OSA on retinal microvascular function. METHODS: We conducted a multi-centre, double-blind, randomised, parallel, controlled trial in patients with known moderate-to-severe OSA, established on continuous positive airway pressure (CPAP). Participants were randomised to 14 nights of either continued CPAP or sham CPAP to generate a return of OSA. Retinal vascular responses to flickering light were measured using dynamic vessel analysis both at baseline and after 14 nights of intervention. The primary outcome was the change from baseline to follow-up in the area under the curve of the arteriolar response to flickering light, sham CPAP versus continued CPAP. RESULTS: Nineteen patients were randomised to sham CPAP, and 18 patients were randomised to continued CPAP. There was no significant effect of CPAP withdrawal and return of OSA on retinal responses, with a change in the area under the curve of the arteriole response to flickering light of + 3.8 arbitrary units (95% CI - 10.6 to + 18.2, p = 0.59), sham CPAP versus continued CPAP. CONCLUSIONS: CPAP withdrawal and a return of OSA had no significant effect on retinal microvascular responses. This contrasts with the effect of CPAP withdrawal on macrovascular endothelial function and suggests that OSA has different effects on macrovascular and microvascular endothelial function. ISRCTN 78082983, 23/10/2014, Prospectively registered.

Medium-Term Outcomes in Severely to Critically Ill Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

BACKGROUND: The medium- and long-term effects of severe acute respiratory syndrome coronavirus 2 infection on survivors are unknown. In the current study, we assessed the medium-term effects of coronavirus disease 2019 (COVID-19) on survivors of severe disease. METHODS: This is a retrospective, case series of 200 patients hospitalized across 3 large Birmingham hospitals with severe-to-critical COVID-19 infection 4-7 months from disease onset. Patients underwent comprehensive clinical, laboratory, imaging, lung function tests (LFTs), and quality of life and cognitive assessments. RESULTS: At 4-7 months after disease onset, 63.2% of patients reported persistent breathlessness; 53.5%, significant fatigue; 37.5%, reduced mobility; and 36.8% pain. Serum markers of inflammation and organ injuries that persisted at hospital discharge had normalized on follow-up, indicating no sustained immune response causing chronic maladaptive inflammation. Chest radiographs showed complete resolution in 82.8%, and significant improvement or no change in 17.2%. LFTs revealed gas transfer abnormalities in 80.0% and abnormal spirometric values in 37.6% of patients. Compared with patients who did not experience breathlessness, those who did had significantly higher incidences of comorbid conditions and residual chest radiographic and LFT abnormalities (P < .01 to all). For all parameters assessed and persisting symptoms there were no significant differences between patients in hospital wards and those in intensive treatment units. All patients reported a significantly reduced quality of life in all domains of the EQ-5D-5L quality-of-life measures. CONCLUSIONS: A significant proportion of severely ill patients with COVID-19 still experience symptoms of breathlessness, fatigue, pain, reduced mobility, depression and reduced quality of life 4-7 months after disease onset. Symptomatic patients tend to have more residual chest radiographic and LFT abnormalities.

ERS/ATS technical standard on interpretive strategies for routine lung function tests.

BACKGROUND: Appropriate interpretation of pulmonary function tests (PFTs) involves the classification of observed values as within/outside the normal range based on a reference population of healthy individuals, integrating knowledge of physiological determinants of test results into functional classifications and integrating patterns with other clinical data to estimate prognosis. In 2005, the American Thoracic Society (ATS) and European Respiratory Society (ERS) jointly adopted technical standards for the interpretation of PFTs. We aimed to update the 2005 recommendations and incorporate evidence from recent literature to establish new standards for PFT interpretation. METHODS: This technical standards document was developed by an international joint Task Force, appointed by the ERS/ATS with multidisciplinary expertise in conducting and interpreting PFTs and developing international standards. A comprehensive literature review was conducted and published evidence was reviewed. RESULTS: Recommendations for the choice of reference equations and limits of normal of the healthy population to identify individuals with unusually low or high results are discussed. Interpretation strategies for bronchodilator responsiveness testing, limits of natural changes over time and severity are also updated. Interpretation of measurements made by spirometry, lung volumes and gas transfer are described as they relate to underlying pathophysiology with updated classification protocols of common impairments. CONCLUSIONS: Interpretation of PFTs must be complemented with clinical expertise and consideration of the inherent biological variability of the test and the uncertainty of the test result to ensure appropriate interpretation of an individual's lung function measurements.

Lung function and breathing patterns in hospitalised COVID-19 survivors: a review of post-COVID-19 Clinics.

INTRODUCTION: There is relatively little published on the effects of COVID-19 on respiratory physiology, particularly breathing patterns. We sought to determine if there were lasting detrimental effect following hospital discharge and if these related to the severity of COVID-19. METHODS: We reviewed lung function and breathing patterns in COVID-19 survivors > 3 months after discharge, comparing patients who had been admitted to the intensive therapy unit (ITU) (n = 47) to those who just received ward treatments (n = 45). Lung function included spirometry and gas transfer and breathing patterns were measured with structured light plethysmography. Continuous data were compared with an independent t-test or Mann Whitney-U test (depending on distribution) and nominal data were compared using a Fisher's exact test (for 2 categories in 2 groups) or a chi-squared test (for > 2 categories in 2 groups). A p-value of < 0.05 was taken to be statistically significant. RESULTS: We found evidence of pulmonary restriction (reduced vital capacity and/or alveolar volume) in 65.4% of all patients. 36.1% of all patients has a reduced transfer factor (TLCO) but the majority of these (78.1%) had a preserved/increased transfer coefficient (KCO), suggesting an extrapulmonary cause. There were no major differences between ITU and ward lung function, although KCO alone was higher in the ITU patients (p = 0.03). This could be explained partly by obesity, respiratory muscle fatigue, localised microvascular changes, or haemosiderosis from lung damage. Abnormal breathing patterns were observed in 18.8% of subjects, although no consistent pattern of breathing pattern abnormalities was evident. CONCLUSIONS: An "extrapulmonary restrictive" like pattern appears to be a common phenomenon in previously admitted COVID-19 survivors. Whilst the cause of this is not clear, the effects seem to be similar on patients whether or not they received mechanical ventilation or had ward based respiratory support/supplemental oxygen.

Reference equations for tidal breathing parameters using structured light plethysmography.

Tidal breathing measurements can be used to identify changes in respiratory status. Structured light plethysmography (SLP) is a non-contact tidal breathing measurement technique. Lack of reference equations for SLP parameters makes clinical decision-making difficult. We have developed a set of growth-adjusted reference equations for seven clinically pertinent parameters of respiratory rate (f R), inspiratory time (t I), expiratory time (t E), duty cycle (t I/total breath time), phase (thoraco-abdominal asynchrony (TAA)), relative thoracic contribution (RTC) and tidal inspiratory/expiratory flow at 50% volume (IE50). Reference equations were developed based on a cohort of 198 seated healthy subjects (age 2-75 years, height 82-194 cm, 108 males). We adopted the same methodological approach as the Global Lung Function Initiative (GLI) report on spirometric reference equations. 5 min of tidal breathing was recorded per subject. Parameters were summarised with their medians. The supplementary material provided is an integral part of this work and a reference range calculator is provided therein. We found predicted f R to decrease with age and height rapidly in the first 20 years and slowly thereafter. Expected t I, t E and RTC followed the opposite trend. RTC was 6.7% higher in females. Duty cycle increased with age, peaked at 13 years and decreased thereafter. TAA was high and variable in early life and declined rapidly with age. Predicted IE50 was constant, as it did not correlate with growth. These reference ranges for seven key measures ensure that clinicians and researchers can identify tidal breathing patterns in disease and better understand and interpret SLP and tidal breathing data.

Health-Related Quality of Life of People Living with COPD in a Semiurban Area of Western Nepal: A Community-Based Study.

Chronic Obstructive Pulmonary Disease (COPD) is a major cause of morbidity and mortality in Nepal. It is a progressive lung disease and has a significant impact on the quality of life of patients. Health-related quality of life (HRQOL) reflects the health- and disease-related facets of quality of life. Limited studies have assessed the impact of COPD on HRQOL and associated factors in Nepal. This study is based on a cross-sectional household survey data from a semiurban area of Western Nepal. A validated Nepali version of St George's Respiratory Questionnaire (SGRQ) was used to measure the HRQOL. COPD was defined together with post-bronchodilator airflow obstruction and the presence of respiratory symptoms. Post-bronchodilator airflow obstruction was defined as Forced Expiratory Volume in 1st second (FEV1) to Forced Vital Capacity (FVC) ratio < 0.70. COPD was diagnosed in 122 participants, and their median (IQR) total score of HRQOL was 40 (26 - 69); the score of symptoms, activity, and impact area were 53 (37 - 74), 57 (36 - 86), and 26 (13 - 62), respectively. The overall HRQOL was significantly different in terms of age, occupational status, physical activity, and comorbidities. Disease severity and the presence of respiratory symptoms had a significant difference in HRQOL (p = 0.0001). Appropriate measures to improve conditions and addressing the associated factors like respiratory symptoms and enhancing physical activity are necessary and important.

Reduction in T LCO and survival in a clinical population.

BACKGROUND: How best to express the level of transfer factor of the lung for carbon monoxide (T LCO) has not been properly explored. METHODS: We used the most recent clinical data from 13 829 patients (54% male; 10% non-European ancestry; median age 60.5 years, range 20-97 years; median survival 3.5 years, range 0-20 years) to determine how best to express T LCO function in terms of its relationship to survival. RESULTS: The proportion of subjects of non-European ancestry with Global Lung Function Initiative (GLI) T LCO z-scores above predicted was reduced, but was significantly increased between -1.5 and -3.5, suggesting the need for ethnicity-appropriate equations. Applying GLI forced vital capacity (FVC) ethnicity methodology to GLI T LCO z-scores removed this ethnic bias and was used for all subsequent analysis. T LCO z-scores using the GLI equations were compared with Miller's USA equations with median T LCO z-scores being -1.43 and -1.50 for GLI and Miller equations, respectively (interquartile range -2.8 to -0.3 and -2.4 to -0.7, respectively). GLI T LCO z-scores gave the best Cox regression model for predicting survival. A previously proposed six-tier grading system for level of lung function did not show much separation in survival risk in the less-severe grades. A new four-tier grading based on z-scores of -1.645, -3 and -5 showed better separation of risk with hazard ratio for all-cause mortality of 2.0, 3.4 and 6.6 with increasing severity. CONCLUSION: Applying GLI FVC ethnicity methodology to GLI T LCO predictions to remove ethnic bias together with a new four-tier z-score grading best relates T LCO function to survival.

Official ERS technical standard: Global Lung Function Initiative reference values for static lung volumes in individuals of European ancestry.

BACKGROUND: Measurement of lung volumes across the life course is critical to the diagnosis and management of lung disease. The aim of the study was to use the Global Lung Function Initiative methodology to develop all-age multi-ethnic reference equations for lung volume indices determined using body plethysmography and gas dilution techniques. METHODS: Static lung volume data from body plethysmography and gas dilution techniques from individual, healthy participants were collated. Reference equations were derived using the LMS (lambda-mu-sigma) method and the generalised additive models of location shape and scale programme in R. The impact of measurement technique, equipment type and being overweight or obese on the derived lung volume reference ranges was assessed. RESULTS: Data from 17 centres were submitted and reference equations were derived from 7190 observations from participants of European ancestry between the ages of 5 and 80 years. Data from non-European ancestry populations were insufficient to develop multi-ethnic equations. Measurements of functional residual capacity (FRC) collected using plethysmography and dilution techniques showed physiologically insignificant differences and were combined. Sex-specific reference equations including height and age were developed for total lung capacity (TLC), FRC, residual volume (RV), inspiratory capacity, vital capacity, expiratory reserve volume and RV/TLC. The derived equations were similar to previously published equations for FRC and TLC, with closer agreement during childhood and adolescence than in adulthood. CONCLUSIONS: Global Lung Function Initiative reference equations for lung volumes provide a generalisable standard for reporting and interpretation of lung volumes measurements in individuals of European ancestry.

Prevalence of Chronic Obstructive Pulmonary Disease and its Associated Factors in Nepal: Findings from a Community-based Household Survey.

Background: Despite chronic obstructive pulmonary disease (COPD) being the commonest non-communicable disease in Nepal, there is limited research evidence estimating the spirometry-based burden of COPD. This study aims to estimate the prevalence of COPD and its correlates through a community-based survey in Pokhara Metropolitan City, a semi-urban area of Western Nepal. Methods: A cross-sectional household survey was conducted among 1459 adults ≥40 years. COPD was defined according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria as a post-bronchodilator ratio of forced expiratory volume in 1st second (FEV1) to forced vital capacity (FVC) <0.70 with the presence of symptoms. COPD was also defined by the lower limit of normal (LLN) threshold - FEV1/FVC < LLN cut-off values with the presence of symptoms. Study participants were interviewed about sociodemographic and behavioural characteristics and respiratory symptoms. Descriptive statistics and logistic regression analysis were applied. Results: Spirometry reports were acceptable in 1438 participants. The mean age of the participants was 55 (±10) years, and, 54% were female. The prevalence of GOLD-defined COPD was 8.5% (95% CI: 7.1-10.0) and based on the LLN threshold of 5.4% (95% CI: 4.2-6.6). The multivariate logistic regression showed that increasing age, low body mass index, illiterate, current or former smoker, and biomass fuel smoke increased the odds of COPD in both the definitions. Conclusion: COPD is highly prevalent at community level and often underdiagnosed. Strategies aiming at early diagnosis and treatment of COPD, especially for the elderly, illiterate, and reducing exposure to smoking and biomass fuel smoke and childhood lung infection could be effective.