Association of clinically significant obstructive sleep apnoea with risks of contracting COVID-19 and serious COVID-19 complications: a retrospective population-based study of health administrative data.

RATIONALE/OBJECTIVES: Despite plausible pathophysiological mechanisms, more research is needed to confirm the relationship between obstructive sleep apnoea (OSA) and the risk of COVID-19 infection or COVID-19-related serious complications. METHODS: We conducted a retrospective population-based cohort study using provincial health administrative data (Ontario, Canada). Adults with physician-diagnosed OSA who received positive airway pressure therapy in the 5 years prepandemic (OSA group) were propensity score matched by baseline characteristics to individuals in the general population at low risk of OSA (non-OSA group) using inverse probability of treatment weighting. Weighted HRs of (1) a positive COVID-19 test and (2) COVID-19-related emergency department (ED) visits, hospitalisations, intensive care unit (ICU) admissions and mortality, within 12 months of pandemic onset, were compared between groups. We also evaluated the impact of comorbid cardiometabolic or chronic airways disease. RESULTS: We identified and matched 324 029 individuals in the OSA group to 4 588 200 individuals in the non-OSA group. Compared with the non-OSA group, those in the OSA group were at a greater hazard of testing positive for COVID-19 (HR=1.17, 95% CI 1.13 to 1.21), having a COVID-19-related ED visit (HR=1.62, 95% CI 1.51 to 1.73), hospitalisation (HR=1.50, 95% CI 1.37 to 1.65) or ICU admission (HR=1.53, 95% CI 1.27 to 1.84). COVID-19-related 30-day mortality was not different (HR=0.98, 95% CI 0.82 to 1.16).We found that for the OSA group, comorbid airways disease but not cardiometabolic conditions increased the hazards of COVID-19-related outcomes, including mortality. CONCLUSION: In this large population-based study, we demonstrated that a recent diagnosis of OSA requiring treatment was associated with an increased hazard of testing positive for COVID-19 and serious COVID-19-related complications, particularly in those with co-existing chronic airways disease.

Identification of Sleep Medicine and Anesthesia Core Topics for Anesthesia Residency: A Modified Delphi Technique Survey.

BACKGROUND: Sleep disorders affect up to 25% of the general population and are associated with increased risk of adverse perioperative events. The key sleep medicine topics that are most important for the practice of anesthesiology have not been well-defined. The objective of this study was to determine the high-priority sleep medicine topics that should be included in the education of anesthesia residents based on the insight of experts in the fields of anesthesia and sleep medicine. METHODS: We conducted a prospective cross-sectional survey of experts in the fields of sleep medicine and anesthesia based on the Delphi technique to establish consensus on the sleep medicine topics that should be incorporated into anesthesia residency curricula. Consensus for inclusion of a topic was defined as >80% of all experts selecting "agree" or "strongly agree" on a 5-point Likert scale. Responses to the survey questions were analyzed with descriptive statistical methods and presented as percentages or weighted mean values with standard deviations (SD) for Likert scale data. RESULTS: The topics that were found to have 100% agreement among experts were the influence of opioids and anesthetics on control of breathing and upper airway obstruction; potential interactions of wake-promoting/hypnotic medications with anesthetic agents; effects of sleep and anesthesia on upper airway patency; and anesthetic management of sleep apnea. Less than 80% agreement was found for topics on the anesthetic implications of other sleep disorders and future pathways in sleep medicine and anesthesia. CONCLUSIONS: We identify key topics of sleep medicine that can be included in the future design of anesthesia residency training curricula.

Morbidity and mortality reduction associated with polysomnography testing in idiopathic pulmonary fibrosis: a population-based cohort study.

BACKGROUND: It is not well-known if diagnosing and treating sleep breathing disorders among individuals with idiopathic pulmonary fibrosis (IPF) improves health outcomes. We evaluated the association between receipt of laboratory-based polysomnography (which is the first step in the diagnosis and treatment of sleep breathing disorders in Ontario, Canada) and respiratory-related hospitalization and all-cause mortality among individuals with IPF. METHODS: We used a retrospective, population-based, cohort study design, analyzing health administrative data from Ontario, Canada, from 2007 to 2019. Individuals with IPF were identified using an algorithm based on health administrative codes previously developed by IPF experts. Propensity score matching was used to account for potential differences in 41 relevant covariates between individuals that underwent polysomnography (exposed) and individuals that did not undergo polysomnography (controls), in order minimize potential confounding. Respiratory-related hospitalization and all-cause mortality were evaluated up to 12 months after the index date. RESULTS: Out of 5044 individuals with IPF identified, 201 (4.0%) received polysomnography, and 189 (94.0%) were matched to an equal number of controls. Compared to controls, exposed individuals had significantly reduced rates of respiratory-related hospitalization (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.24-0.75), p = 0.003) and all-cause mortality (HR 0.49, 95% CI 0.30-0.80), p = 0.004). Significantly reduced rate of respiratory-related hospitalization (but not all-cause mortality) was also observed among those with > = 1 respiratory-related hospitalization (HR 0.38, 95% CI 0.15-0.99) and systemic corticosteroid receipt (HR 0.37, 95% CI 0.19-0.94) in the year prior to the index date, which reflect sicker subgroups of persons. CONCLUSIONS: Undergoing polysomnography was associated with significantly improved clinically-important health outcomes among individuals with IPF, highlighting the potential importance of incorporating this testing in IPF disease management.

Dissociation between objectively quantified snoring and sleep quality.

BACKGROUND: The impact of simple snoring on sleep structure and sleepiness has not been well described. In several studies, self-reported snoring was associated with increased daytime sleepiness. However, most studies did not distinguish patients with simple snoring from those with coexisting obstructive sleep apnea (OSA) using objective measures. We therefore evaluated the relationship between objectively measured snoring and both sleep structure and daytime sleepiness in patients with no or mild OSA. METHODS: Subjects referred for suspected sleep disorders underwent polysomnography (PSG) during which breath sounds were recorded by a microphone. Those with an apnea-hypopnea index (AHI) <15/h were analyzed. Individual snores were identified by a computer algorithm, from which the snore index (SI) was calculated as the number of snores/h of sleep. Sleep stages and arousals were quantified. Daytime sleepiness was evaluated using the Epworth Sleepiness Scale (ESS) score. RESULTS: 74 (35 males) subjects were included (age, mean ±â€¯SD: 46.4 ±â€¯15.3 years and body mass index: 29.8 ±â€¯7.0 kg/m2). The mean SI was 266 ±â€¯243 snores/h. Subjects were categorized according to their SI into 3 tertiles: SI < 100, between 100-350, and >350. No sleep structure indeces, arousals, or ESS score differed among SI tertiles (p > 0.13). There was no correlation between SI and any of these variables (p > 0.29). In contrast, the AHI was significantly related to frequency of arousals (r = 0.23, p = 0.048). CONCLUSIONS: These findings suggest that simple snoring assessed objectively is not related to indices of sleep structure or subjective sleepiness.

Risk of major cardiovascular and cerebrovascular complications after elective surgery in patients with sleep-disordered breathing: A retrospective cohort analysis.

BACKGROUND: There is limited and conflicting data on whether sleep-disordered breathing (SDB) is associated with postoperative major cardiovascular and cerebrovascular events (MACCE), and mortality. OBJECTIVES: To determine whether SDB is associated with increased risks of MACCE, mortality and length of hospital stay. DESIGN: Retrospective cohort analysis from the Nationwide Inpatient Sample. SETTING: Adults who underwent elective abdominal, orthopaedic, prostatic, gynaecological, thoracic, transplant, vascular or cardiac surgery in the United States of America between 2011 and 2014. PATIENTS: The study cohort included 1813 974 surgical patients, of whom 185 615 (10.2%) had SDB. Emergency or urgent surgical procedures were excluded. MAIN OUTCOME MEASURES: The incidences of MACCE, respiratory and vascular complications, in-hospital mortality and mean length of hospital stay were stratified by SDB. Linear and logistic regression models were constructed to determine the independent association between SDB and outcomes of interest. RESULTS: The incidences of MACCE [25.3 vs. 19.8%, odds ratio (OR) 1.20, P < 0.001] and respiratory complications (11.75 vs. 8.0%, OR 1.43, P < 0.001) were significantly higher in patients with SDB than in those without SDB. SDB was associated with higher rates of atrial fibrillation (14.7 vs. 10.8%, P < 0.001), other arrhythmias (6.0 vs. 5.4%, P < 0.001) and congestive heart failure (9.8 vs. 7.1%, P < 0.001). SDB patients had a lower rate of myocardial infarction (3.1 vs. 3.4%, OR 0.69, P < 0.001), lower mortality (0.6 vs. 1.3%, P < 0.001) and shorter length of hospital stay (4.8 vs. 5.2 days, P < 0.001). CONCLUSION: SDB was associated with increased risks of MACCE, and respiratory and vascular complications, but had a lower incidence of in-hospital mortality and shorter length of hospital stay.

Temporal shifts in fluid in pulmonary hypertension with and without sleep apnea.

Overnight extracellular rostral fluid shifts have been shown to be of importance in patients with fluid-retaining states and are associated with a higher prevalence of sleep apnea. Pulmonary hypertension is frequently associated with right ventricular dysfunction and progressive right ventricular failure, and an increased prevalence of sleep apnea has been described. In light of the importance of fluid shifts in the pathophysiology of sleep apnea, we aimed to explore temporal fluid shifts in patients with pulmonary hypertension with and without sleep apnea. Patients with pulmonary hypertension (WHO Group 1 or 4) had overnight extracellular rostral fluid shift assessment before and a minimum of 3 months after initiation of pulmonary hypertension-specific therapy. Fluid shift measurements of extracellular leg, abdominal, thoracic and neck fluid volumes were performed simultaneously. Twenty-nine patients with pulmonary hypertension (age 55 ± 16 years, 69% female) participated. Sleep apnea was diagnosed in 15 subjects (apnea-hypopnea index 14 [8-27] per hr). There were no significant differences in baseline or overnight leg extracellular rostral fluid, abdominal extracellular rostral fluid, thoracic extracellular rostral fluid or neck extracellular rostral fluid between those with and without sleep apnea. There was a significant inverse correlation between the sleep apnea severity and the overnight change in leg extracellular rostral fluid (r = -0.375, p = 0.049). There were no significant differences detected in overnight extracellular rostral fluid shifts from baseline to follow-up. Treatment-naïve patients with pulmonary hypertension both with and without sleep apnea demonstrate overnight extracellular rostral fluid shifts from the legs into the thorax and neck. Pulmonary hypertension-specific treatment, while significantly improving cardiac haemodynamics, had little impact on nocturnal extracellular rostral fluid shifts or the presence of sleep apnea.

The prevalence of obstructive sleep apnea in mild cognitive impairment: a systematic review.

BACKGROUND: Previous studies have shown that obstructive sleep apnea (OSA) is associated with a higher risk of cognitive impairment or dementia in the elderly, leading to deleterious health effects and decreasing quality of life. This systematic review aims to determine the prevalence of OSA in patients with mild cognitive impairment (MCI) and examine whether an association between OSA and MCI exists. METHODS: We searched Medline, PubMed, Embase, Cochrane Central, Cochrane Database of Systematic Reviews, PsychINFO, Scopus, the Web of Science, ClinicalTrials.gov and the International Clinical Trials Registry Platform for published and unpublished studies. We included studies in adults with a diagnosis of MCI that reported on the prevalence of OSA. Two independent reviewers performed the abstract and full-text screening, data extraction and the study quality critical appraisal. RESULTS: Five studies were included in the systematic review. Overall, OSA prevalence rates in patients with MCI varied between 11 and 71% and were influenced by OSA diagnostic methods and patient recruitment locations (community or clinic based). Among studies using the following OSA diagnostic measures- self-report, Home Sleep Apnea Testing, Berlin Questionnaire and polysomnography- the OSA prevalence rates in MCI were 11, 27, 59 and 71%, respectively. In a community-based sample, the prevalence of OSA in patients with and without MCI was 27 and 26%, respectively. CONCLUSIONS: Based on limited evidence, the prevalence of OSA in patients with MCI is 27% and varies based upon OSA diagnostic methods and patient recruitment locations. Our findings provide an important framework for future studies to prospectively investigate the association between OSA and MCI among larger community-based cohorts and implement a standardized approach to diagnose OSA in memory clinics. PROSPERO REGISTRATION: CRD42018096577.

Short- and long-term continuous positive airway pressure usage in the post-stroke population with obstructive sleep apnea.

PURPOSE: Obstructive sleep apnea (OSA) is highly prevalent in post-stroke patients and observational evidence suggests that untreated it is a harbinger of poorer outcomes in this population. Clinical trials on the impact of treatment of OSA with continuous positive airway pressure (CPAP) have countered difficulties with patient engagement and adherence to CPAP therapy. Real-world data on continuous positive airway pressure initiation and usage in the post-stroke population with obstructive sleep apnea is limited. METHODS: We performed a clinical retrospective study between January 2006 and June 2015 to describe the short- and long-term CPAP usage in the post-stroke population with OSA, and to assess which patient, disease, and treatment-related factors were associated with CPAP purchase, initiation, and usage in this population. RESULTS: Of 191 post-stroke patients' recommended CPAP therapy, post-prescription usage at 3, 6, 12, 24, and 60 months was 58%, 53%, 48%, 45%, and 39% respectively. OSA severity-related factors, such as AHI or degree of nocturnal hypoxemia, were not significantly associated with CPAP usage. Predictors of CPAP usage at all time points were younger age, male sex, never smokers, and no history of hypertension. There were some differences in predictors of CPAP usage between early and later time periods. CONCLUSIONS: We demonstrated that the long-term usage of CPAP therapy is possible with most of the attrition occurring in the first 3 months. Upfront healthcare resource allocation to CPAP initiation and usage in this population may improve longer-term usage.

Evaluation of Cerebrovascular Reactivity in Subjects with and without Obstructive Sleep Apnea.

BACKGROUND: Both obstructive sleep apnea (OSA) and altered cerebrovascular reactivity (CVR) are associated with increased stroke risk. Nevertheless, the incidence of abnormal CVR in patients with OSA is uncertain due to the high variability in the way CVR is measured both within and between studies. We hypothesized that a standardized CVR with a consistent vasoactive stimulus and cerebral blood flow (CBF) measure would be reduced in patients with severe OSA compared with healthy controls. METHODS: This was a prospective study in which subjects with and without OSA were administered a standardized hypercapnic stimulus, and CBF was monitored by blood oxygen level-dependent magnetic resonance signal changes, a high space and time resolved surrogate for CBF. RESULTS: Twenty-four subjects with OSA (mean age 45.9 years, apnea-hypopnea index [AHI] 26.8 per hour) and 6 control subjects (mean age 42.8 years, AHI 2.4 per hour) were included. Compared with controls, subjects with OSA had a significantly greater whole brain (.1565 versus .1094, P = .013), gray matter (.2077 versus .1423, P = .009), and white matter (.1109 versus .0768, P = .024) CVR, respectively. CONCLUSIONS: Contrary to expectations, subjects with OSA had greater CVR compared with control subjects.

In-hospital diagnosis of sleep apnea in stroke patients using a portable acoustic device.

PURPOSE: Sleep apnea (SA) is highly prevalent in post-stroke patients. Due to physical disability and relative inaccessibility of polysomnography (PSG) to test for SA, patients with stroke frequently remain undiagnosed and untreated. Portable SA monitoring can facilitate at-home or in-hospital testing for SA. However, portable SA monitoring is not recommended in those with complex medical conditions, such as stroke, due to the lack of validation of portable monitoring in such patients. METHODS: The objective of our study was to test the accuracy and feasibility of a portable single-channel acoustic device, BresoDx™ for quantifying the apnea-hypopnea index (AHI) and diagnosing SA in a post-stroke population. Patients who recently suffered a stroke and were undergoing rehabilitation in a stroke rehabilitation unit (SRU) underwent testing with BresoDx both simultaneously during attended PSG and unattended on the SRU. RESULTS: We studied 23 stroke patients of whom 78% had SA (defined by AHI ≥15) on PSG. All of the patients tolerated the BresoDx. Using cutoff AHI of ≥15 by PSG to diagnose SA, BresoDx had sensitivity of 90.0%, specificity of 84.6%, and overall accuracy of 87.0% in the laboratory. CONCLUSIONS: This study demonstrates that BresoDx is well tolerated and feasible to use in the post-stroke population where it was found to have excellent positive and negative predictive values for the diagnosis of SA.

Significance of obstructive sleep apnea in the patient with pulmonary hypertension.

PURPOSE OF REVIEW: The purpose of this review was to evaluate the consequence of obstructive sleep apnea (OSA) in pulmonary hypertension by reviewing the current literature and understanding potential pathophysiological mechanisms. RECENT FINDINGS: Small studies have suggested a high prevalence of comorbid OSA in those with known pulmonary hypertension. Pathophysiological mechanisms are highly suggestive of potential deleterious effect of OSA on pulmonary hemodynamics. SUMMARY: Clearly, current research work on comorbid OSA and pulmonary hypertension is still in its infancy and the field is ripe for future investigation. The significance of OSA in this population has yet to be fully determined.

Sleep breathing disorder frequency, risk factors, and treatment among adults with cystic fibrosis.

BACKGROUND: Our understanding of the epidemiology of sleep breathing disorders among adults with cystic fibrosis (CF) is limited. Our purpose was to describe the frequency, risk factors and treatment of sleep breathing disorders among adults with CF. METHODS: This was a retrospective analysis of linked data from laboratory-based diagnostic polysomnography (PSG) undertaken at St. Michael's Hospital (Toronto, Canada) and the Canadian CF Registry. Adults (≥19 years old) with CF that underwent a diagnostic PSG at St. Michael's Hospital between 2002 and 2021 were included. Sleep breathing disorder frequency, risk factors, and treatment were described, using descriptive statistics and logistic regression. RESULTS: There were 42 patients included (33.3 % women and median age at diagnostic PSG was 34.7 years). Obstructive sleep apnea [OSA] was the most commonly observed sleep breathing disorder (found in 64.3 %), followed by sustained nocturnal hypoxemia (16.7 %), and sleep hypoventilation (9.5 %). Only 41 % of individuals with an elevated total apnea-hypopnea index were receiving positive airway pressure [PAP] therapy. Corticosteroid use (either oral or inhaled) was the only factor with a significant positive association with presence of any sleep breathing disorder (odds ratio 5.00, 95 % confidence interval 1.28-22.78). CONCLUSIONS: Among adults with CF, OSA occurs more commonly than previously appreciated and the majority of sleep breathing disorders were not being treated with PAP or supplemental oxygen. Management of sleep breathing disorders among adults with CF reflects a potentially important care gap, but further research is needed to determine the health impacts of treating sleep breathing disorders in CF.

Effects of donor smoking history on early post-transplant lung function measured by oscillometry.

Introduction: Prior studies assessing outcomes of lung transplants from cigarette-smoking donors found mixed results. Oscillometry, a non-invasive test of respiratory impedance, detects changes in lung function of smokers prior to diagnosis of COPD, and identifies spirometrically silent episodes of rejection post-transplant. We hypothesise that oscillometry could identify abnormalities in recipients of smoking donor lungs and discriminate from non-smoking donors. Methods: This prospective single-center cohort study analysed 233 double-lung recipients. Oscillometry was performed alongside routine conventional pulmonary function tests (PFT) post-transplant. Multivariable regression models were constructed to compare oscillometry and conventional PFT parameters between recipients of lungs from smoking vs non-smoking donors. Results: The analysis included 109 patients who received lungs from non-smokers and 124 from smokers. Multivariable analysis identified significant differences between recipients of smoking and non-smoking lungs in the oscillometric measurements R5-19, X5, AX, R5z and X5z, but no differences in %predicted FEV1, FEV1/FVC, %predicted TLC or %predicted DLCO. An analysis of the smoking group also demonstrated associations between increasing smoke exposure, quantified in pack years, and all the oscillometry parameters, but not the conventional PFT parameters. Conclusion: An interaction was identified between donor-recipient sex match and the effect of smoking. The association between donor smoking and oscillometry outcomes was significant predominantly in the female donor/female recipient group.

Respiratory oscillometry with CT image analysis in idiopathic pulmonary fibrosis following single lung transplant.

Oscillometry is an emerging pulmonary function testing tool that is conducted during tidal breaths with minimal patient effort. It is highly sensitive to changes in lung mechanics. Oscillometry was recently shown to be highly associated with disease severity in idiopathic pulmonary fibrosis (IPF). The usefulness of oscillometry after single lung transplant in IPF patients is not well understood. Our study demonstrated that oscillometry can detect changes in the graft despite presence of a native fibrotic lung to provide useful information to complement spirometry.

A comprehensive evaluation of online inhaler use techniques for obstructive airway disease.

BACKGROUND: Pulmonary inhaler therapy is a core treatment modality for >600 million individuals affected by obstructive airways disease globally. Poor inhaler technique is associated with reduced disease control and increased health care utilization; however, many patients rely on the internet as a technical resource. This study assesses the content and quality of online resources describing inhaler techniques. METHODS: A Google search was conducted in April 2023 capturing the top 5 search results for 12 common inhaler devices. Websites were compared to product monographs for preparation/first use, inhalational technique, and post-usage/device care. They were also assessed using accepted quality metrics (GQS, DISCERN, JAMA Benchmark scores) and clinically relevant aspects based on the literature and consensus statements. RESULTS: Websites regularly excluded critical steps important for proper inhaler technique. They performed best on information related directly to inhalation technique (average median score 78%), whereas steps related to preparation/first use (58%) or post-usage/device care (50%) were less frequently addressed. Median GQS, DISCERN, and JAMA Benchmark scores were 3 [IQR 3-4], 3 [IQR 2-4], and 1 [IQR 1-3], respectively. Clinically relevant factors were only addressed in about one-fifth of websites with no websites addressing smoking cessation, environmental considerations, or risk factors for poor technique. CONCLUSIONS: This study highlights gaps in online resources describing inhaler technique, particularly related to preparation/first use and post-usage/device care steps. Clinically relevant factors were rarely addressed across websites. Improvements in these areas could lead to enhanced inhaler technique and clinical outcomes.

The association between sleep quality and obstructive sleep apnea with health-related quality of life in children with obesity.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) and poor sleep quality are highly prevalent in children with obesity, but their individual associations with health-related quality of life (HRQOL) are unknown in this population. The primary objective was to describe the independent association of OSA and sleep quality with HRQOL in children with obesity. METHODS: This was a cross-sectional study of children with obesity at 2 tertiary care centers. Sleep quality and HRQOL were measured with the Pittsburgh Sleep Quality Index and Pediatric Quality of Life Inventory questionnaires, respectively. Multivariable regression models were created to evaluate associations between OSA and sleep quality with HRQOL. RESULTS: There were 98 children (median age 15.0 years, median body mass index z-score 3.8, 44% females). Among the study population, 49/98 (50%) children reported poor sleep quality, 41/98 (42%) children had OSA, and 52/98 (53%) children reported impaired HRQOL. Self-reported poor sleep quality was independently associated with reduced HRQOL, whereas the presence of OSA was not. Children with poor sleep quality had a reduced Pediatric Quality of Life Inventory score by 8.8 compared to children with good sleep quality (95% confidence interval, 2.6-14.9; P = .006), when adjusting for age, sex, body mass index z-score, attention-deficit/hyperactivity disorder, mood/anxiety disorder, and study site. CONCLUSIONS: In the current study of children with obesity, we found that HRQOL was more strongly associated with the self-reported experience of sleep than the presence of OSA. Clinicians should assess and optimize sleep quality as part of the evaluation for OSA in children with obesity. CITATION: Xiao L, Voutsas G, Ryan CM, Katz SL, Narang I. The association between sleep quality and obstructive sleep apnea with health-related quality of life in children with obesity. J Clin Sleep Med. 2023;19(11):1877-1883.

Intra-subject variability in oscillometry correlates with acute rejection and CLAD post-lung transplant.

Background: Chronic lung allograft dysfunction (CLAD) is the major cause of death post-lung transplantation, with acute cellular rejection (ACR) being the biggest contributing risk factor. Although patients are routinely monitored with spirometry, FEV1 is stable or improving in most ACR episodes. In contrast, oscillometry is highly sensitive to respiratory mechanics and shown to track graft injury associated with ACR and its improvement following treatment. We hypothesize that intra-subject variability in oscillometry measurements correlates with ACR and risk of CLAD. Methods: Of 289 bilateral lung recipients enrolled for oscillometry prior to laboratory-based spirometry between December 2017 and March 2020, 230 had ≥ 3 months and 175 had ≥ 6 months of follow-up. While 37 patients developed CLAD, only 29 had oscillometry at time of CLAD onset and were included for analysis. These 29 CLAD patients were time-matched with 129 CLAD-free recipients. We performed multivariable regression to investigate the associations between variance in spirometry/oscillometry and the A-score, a cumulative index of ACR, as our predictor of primary interest. Conditional logistic regression models were built to investigate associations with CLAD. Results: Multivariable regression showed that the A-score was positively associated with the variance in oscillometry measurements. Conditional logistic regression models revealed that higher variance in the oscillometry metrics of ventilatory inhomogeneity, X5, AX, and R5-19, was independently associated with increased risk of CLAD (p < 0.05); no association was found for variance in %predicted FEV1. Conclusion: Oscillometry tracks graft injury and recovery post-transplant. Monitoring with oscillometry could facilitate earlier identification of graft injury, prompting investigation to identify treatable causes and decrease the risk of CLAD.

Evaluation and Management of Dyspnea in Hypermobile Ehlers-Danlos Syndrome and Generalized Hypermobility Spectrum Disorder: Protocol for a Pilot and Feasibility Randomized Controlled Trial.

BACKGROUND: Dyspnea is a prevalent symptom in individuals with hypermobile Ehlers-Danlos Syndrome (hEDS) and generalized hypermobility spectrum disorder (G-HSD), yet its contributors have not been identified. One known contributor to dyspnea is respiratory muscle weakness. The feasibility and effectiveness of inspiratory muscle training (IMT) in combination with standard-of-care rehabilitation (aerobic, resistance, neuromuscular stabilization, and balance and proprioception exercises) in improving respiratory muscle strength and patient-reported outcomes in patients with hEDS or G-HSD have not been evaluated. OBJECTIVE: This study aims to evaluate dyspnea, respiratory muscle strength, and patient-reported outcome measures (PROMs) in hEDS or G-HSD compared with healthy controls and to assess the feasibility of a randomized controlled trial of IMT and standard-of-care rehabilitation for improving respiratory muscle strength, exercise capacity, and PROMs compared with standard-of-care rehabilitation in hEDS and G-HSD. METHODS: The study will include 34 participants with hEDS or G-HSD and 17 healthy, age- and sex-matched controls to compare respiratory muscle structure and function and PROMs. After baseline assessments, participants with hEDS or G-HSD will be randomized into the intervention group and provided IMT combined with Ehlers-Danlos Syndrome standard-of-care rehabilitation or into the usual care group, and provided only standard-of-care rehabilitation for 8 weeks. The intervention group will be prescribed IMT in their home environment using the POWERbreathe K5 IMT device (POWERbreathe International Ltd). IMT will comprise 2 daily sessions of 30 breaths for 5 days per week, with IMT progressing from 20% to 60% of the baseline maximal inspiratory pressure (MIP) over an 8-week period. Feasibility will be assessed through rates of recruitment, attrition, adherence, adverse events, and participant satisfaction. The primary pilot outcome is MIP change over an 8-week period in hEDS or G-HSD. Secondary outcomes will include the evaluation of dyspnea using Medical Research Council Scale and 18-point qualitative dyspnea descriptors; diaphragmatic thickening fraction using ultrasound; respiratory muscle endurance; pulmonary function; prefrontal cortical activity using functional near-infrared spectroscopy; aerobic capacity during cardiopulmonary exercise testing; quality of life using Short Form-36; and scores from the Depression, Anxiety, and Stress scale-21. These measures will also be performed once in healthy controls to compare normative values. Multivariable regression will be used to assess the contributors to dyspnea. Paired 2-tailed t tests will be used to assess the changes in MIP and secondary measures after 8 weeks of IMT. RESULTS: Study recruitment began in August 2021 and, with several disruptions owing to COVID-19, is expected to be completed by December 2023. CONCLUSIONS: This study will provide a better understanding of the factors associated with dyspnea and the feasibility and effectiveness of IMT combined with standard-of-care rehabilitation. IMT may be a novel therapeutic strategy for improving respiratory muscle function and patient-reported outcomes in individuals with hEDS or G-HSD. TRIAL REGISTRATION: ClinicalTrials.gov NCT04972565; https://clinicaltrials.gov/ct2/show/NCT04972565. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/44832.