Comparing treatment effects of a convenient vibratory positional device to CPAP in positional OSA: a crossover randomised controlled trial.

OBJECTIVES: Up to 77% of patients with obstructive sleep apnoea (OSA) have positional OSA (POSA) but traditional positional therapy (PT) methods have failed as they were poorly tolerated. New convenient vibratory PT devices have been invented but while recent studies suggest high treatment efficacy and adherence, there are no published data comparing these devices directly with continuous positive airway pressure (CPAP). Our objective is to evaluate if a convenient vibratory PT device is non-inferior to CPAP in POSA treatment. METHODS: In this crossover randomised controlled trial, we enrolled patients with POSA with significant daytime sleepiness (Epworth Sleepiness Scale (ESS)≥10). POSA diagnosis was based on: (1) total Apnoea/Hypopnoea Index (AHI)>10/hour and non-supine AHI<10/hour (2) supine AHI≥2 × non-supine AHI. Patients used their initial allocated devices (PT or CPAP) for 8 weeks before crossing to the alternative intervention after a 1 week washout. The primary aim is to measure changes in ESS between the two treatments. Secondary outcomes include sleep study parameters and patient treatment preference (ClinicalTrials.gov: NCT03125512). RESULTS: 40 patients completed the trial between April 2017 and December 2018. Difference in ESS after 8 weeks of device use (PT minus CPAP) was 2.0 (95% CI 0.68 to 3.32), exceeding our predetermined non-inferiority margin of 1.5. AHI on CPAP was lower than with PT (4.0±3.2 vs 13.0±13.8 events/hour, respectively, p=0.001), although both were lower than at baseline. Time spent supine was significantly lower with PT than CPAP (p<0.001). 60% of patients preferred CPAP, 20% preferred PT, while 20% preferred neither device. CONCLUSIONS: The non-inferiority ESS endpoint for PT compared with CPAP was not met and the results were inconclusive. Future trials with larger sample sizes or in less symptomatic patients are warranted to provide further insight into the role of these new vibratory PT devices.

Predictors of future exacerbations in a multi-ethnic Asian population with asthma.

OBJECTIVE: Exacerbations are important outcomes in asthma. Risk factors for exacerbations may differ in different populations. Although various demographic and clinical variables were examined in previous studies on exacerbation risks in asthma, important variables such as ethnicity, adherence, and medication titration were not included. This study examined independent predictors of future exacerbations in a multi-ethnic asthma population in Asia, while including the variables of ethnicity, medication adherence, and medication change in our analysis. METHODS: We recruited patients with physician-diagnosed asthma in a tertiary hospital in Singapore over a one-year period. Exacerbations requiring ≥3 days of systemic corticosteroids one year prior to study enrolment (previous exacerbations) and the year following enrolment (future exacerbations) were recorded from electronic medical records. Medication adherence was based on pharmacy refill. An increase or a decrease in the Global Initiative for Asthma treatment steps were considered to be medication up- and down-titration, respectively. A multivariate logistic regression model was constructed to determine independent predictors of future exacerbations. RESULTS: The study cohort of 340 patients comprised mainly of Chinese (53.2%), Malay (32.9%), and Indian (9.7%) ethnicities. After multivariate analysis, only Indian ethnicity (OR 3.75, 95% CI 1.077-13.051, p = 0.038), Asthma Control Test score (OR 0.913, 95% CI 0.839-0.995, p = 0.037), and the number of previous exacerbations (OR 1.84, 95% CI 1.416-2.391, p < 0.001) were independent predictors of future exacerbations. CONCLUSIONS: There are ethnic differences in exacerbation risk in Asian populations. Each incremental worsening of the asthma symptom control score and each additional exacerbation also increases the risk of future exacerbations.

Adherence to Continuous Positive Airway Pressure therapy in Singaporean patients with Obstructive Sleep Apnea.

PURPOSE: To investigate the rates of Continuous Positive Airway Pressure (CPAP) uptake and adherence amongst Singaporean patients diagnosed with Obstructive Sleep Apnea (OSA), and to evaluate factors correlated with CPAP uptake and adherence. STUDY DESIGN: Retrospective review of medical records. METHODS: Medical records were reviewed for baseline demographics, daytime sleepiness, presence of nasal symptoms and OSA severity, initial treatment choice, the rate of CPAP treatment uptake and CPAP adherence at 1 and 12 months. RESULTS: 2160 patients were diagnosed with OSA within the 5-year period (2011-2015). 463 (21.4%) had mild OSA, 583 (27.0%) had moderate OSA and 1114 (51.6%) had severe OSA. For initial therapy, 751 (34.8%) patients opted for a 1-month CPAP trial, 288 (13.3%) patients chose surgery upfront, 291 (13.5%) patients chose adjunctive treatments (weight loss, positional therapy, dental appliance, intranasal steroid spray for allergic rhinitis) and 830 (38.4%) patients rejected all forms of treatment. 337 out of 751 patients (44.9%) were adherent to CPAP therapy during the 1 month trial. 381 out of 751 (50.7%) patients took up CPAP therapy following the trial period, of which 299 out of 381 (78.5%) patients were adherent to CPAP therapy at 1 year. CPAP adherence during the 1-month trial was a predictor for eventual CPAP treatment uptake and CPAP adherence at 1 year (p < 0.001). Age (p < 0.001), BMI (p < 0.001) and normal ESS (p = 0.01) were predictors of treatment rejection. 24 patients underwent upper airway surgery during their first year of using CPAP. 21 out of the 24 patients (87.5%) were adherent to CPAP at 1 year after undergoing surgery. These patients had a higher rate of CPAP adherence compared to the overall cohort (87.5% versus 78.5%), but this was not statistically significant (p > 0.05). CONCLUSION: Singaporean patients who accept CPAP therapy after an initial 1-month CPAP trial will generally be adherent to CPAP therapy. Initial patterns of CPAP usage are predictive of long term CPAP adherence. However, there is a high rate of CPAP treatment rejection both at the time of diagnosis and after the CPAP trial. Upper airway surgery in selected patients may improve CPAP adherence.

Characteristics of non-smoking adult asthma patients with chronic airflow limitation.

OBJECTIVE: Chronic airflow limitation (CAL) can develop in a subgroup of patients with asthma. Characterising these patients is important because reduced lung function is a risk factor for adverse asthma outcomes. We hypothesised that heterogeneity in patients with CAL may be influenced by age at asthma onset. We first compared never-smoking asthma patients with and without CAL, and subsequently examined the differences between patients with late and early-onset asthma within the CAL cohort. METHODS: Patients seen in our hospital's respiratory clinic between 1 Jan 2015 and 31 December 2015 were recruited to the study. CAL was defined as post-bronchodilator forced expiratory volume in 1 second (FEV1)<80% predicted, in the presence of post-bronchodilator ratio <70%. Variables independently associated with CAL were determined using a multivariate logistic regression model. Comparisons between patients with late-onset asthma (age ≥18 years) and early-onset asthma were made within the CAL cohort. RESULTS: 247 patients were included in the study. Age was the only variable independently associated with CAL after regression analysis, with an increase in odds of 3.8% (95% CI 0.4-7.3%) for every 1 year increase in age, p = 0.027. 63.2% of patients with CAL had late-onset asthma. Compared to patients with early-onset asthma, those with late-onset asthma had higher fractional exhaled nitric oxide levels (43 ± 32 ppb vs 20 ± 8 pb, p = 0.008). CONCLUSIONS: An increase in age is associated with CAL in never-smoking asthma patients. In addition, age at asthma onset appears to influence airway inflammation in patients with CAL.

Plasma Metanephrines Yield Fewer False-Positive Results Than Urine Metanephrines in Patients With Obstructive Sleep Apnea.

CONTEXT: Obstructive sleep apnea (OSA) is associated with increased nocturnal sympathetic activity. In OSA patients, elevations in metanephrines may lead to false-positive tests when evaluating for pheochromocytoma or paraganglioma (PPGL). OBJECTIVE: To evaluate whether morning plasma metanephrines would lead to fewer false-positive results than 24-hour urinary metanephrines in OSA patients. METHODS: Patients undergoing polysomnography for suspected OSA were recruited. Plasma free and 24-hour urinary metanephrines were measured by HPLC-MS/MS. Patients with elevated levels had repeat measurements, abdominal imaging, and follow-up to diagnose or exclude a PPGL. RESULTS: Seventy-six patients completed polysomnography and biochemical testing; 68 (89.5%) patients had OSA, of whom 19 (27.9%) had elevated plasma and/or urinary metanephrines. On follow-up, one patient had a bladder paraganglioma, while PPGL was excluded in the remaining patients. OSA patients had more false-positive urinary metanephrines (17 of 67, 25.4%) than plasma metanephrines (2 of 67, 3.0%), P < .01, and this was more common in severe OSA (13 of 34, 38.2%), compared to moderate/mild OSA (4 of 33, 12.1%), P < .01. Both plasma and urinary metanephrines decreased after treatment with continuous positive airway pressure. On multivariable analysis, severe OSA, obesity, and family history of hypertension were positive predictors for false-positive urinary metanephrines in patients with suspected OSA. CONCLUSION: In OSA patients, plasma metanephrines are less likely to yield false-positive results for the diagnosis of PPGL than 24-hour urinary metanephrines. In patients with suspected OSA, obesity, or a family history of hypertension, plasma metanephrines may be the preferred first-line test to avoid unnecessary anxiety or follow-up.

Benchmarking performance of an automatic polysomnography scoring system in a population with suspected sleep disorders.

Aim: The current gold standard for measuring sleep disorders is polysomnography (PSG), which is manually scored by a sleep technologist. Scoring a PSG is time-consuming and tedious, with substantial inter-rater variability. A deep-learning-based sleep analysis software module can perform autoscoring of PSG. The primary objective of the study is to validate the accuracy and reliability of the autoscoring software. The secondary objective is to measure workflow improvements in terms of time and cost via a time motion study. Methodology: The performance of an automatic PSG scoring software was benchmarked against the performance of two independent sleep technologists on PSG data collected from patients with suspected sleep disorders. The technologists at the hospital clinic and a third-party scoring company scored the PSG records independently. The scores were then compared between the technologists and the automatic scoring system. An observational study was also performed where the time taken for sleep technologists at the hospital clinic to manually score PSGs was tracked, along with the time taken by the automatic scoring software to assess for potential time savings. Results: Pearson's correlation between the manually scored apnea-hypopnea index (AHI) and the automatically scored AHI was 0.962, demonstrating a near-perfect agreement. The autoscoring system demonstrated similar results in sleep staging. The agreement between automatic staging and manual scoring was higher in terms of accuracy and Cohen's kappa than the agreement between experts. The autoscoring system took an average of 42.7 s to score each record compared with 4,243 s for manual scoring. Following a manual review of the auto scores, an average time savings of 38.6 min per PSG was observed, amounting to 0.25 full-time equivalent (FTE) savings per year. Conclusion: The findings indicate a potential for a reduction in the burden of manual scoring of PSGs by sleep technologists and may be of operational significance for sleep laboratories in the healthcare setting.

Asthma phenotypes in a multi-ethnic Asian cohort.

BACKGROUND: Identification of asthma phenotypes facilitates our understanding of asthma pathobiologies. Phenotypes observed in homogenous Asian cohorts have distinct differences from those described in Caucasian cohorts, suggesting that ethnicity may influence phenotypic expression. Phenotypic clusters in a multi-ethnic Southeast Asian cohort have not been described before, and direct comparisons of these clusters within a single study may reveal how ethnicity affects phenotypic expression. METHODS: Six hundred and thirty adult asthma patients from two healthcare institutions in Singapore were randomly assigned in a 2:1 fashion to a test and validation cohort. Latent class analysis was performed on both cohorts using age of asthma onset, sex, ethnicity, smoking status, body mass index, lung function, blood eosinophil count, asthma control test score, and exacerbation frequency as input variables. Phenotypic clusters between the test and validation cohorts were compared RESULTS: Three clusters were identified in both the test and validation cohorts, with corresponding clusters of each cohort sharing similar characteristics. Ethnic representation and asthma control were significantly different between clusters. Cluster one comprised Chinese females with late-onset asthma and the best asthma control. Cluster two comprised non-Chinese females with obesity and the worst asthma control. Cluster three was multi-ethnic with the greatest proportion of atopic patients. CONCLUSION: We identified three phenotypic clusters in our multi-ethnic Southeast Asian population, with distinct differences in ethnicity which may be attributable to inherent differences in baseline characteristics among ethnic groups.

Comparison of the Proportion and Healthcare Utilisation of Adult Patients with Uncontrolled Severe Asthma versus Non-Severe Asthma Seen in a Southeast Asian Hospital-Based Respiratory Specialist Clinic.

INTRODUCTION: Understanding the burden of uncontrolled severe asthma is essential for disease-targeted healthcare planning. There is a scarcity of data regarding the proportion, healthcare utilisation and costs of patients with uncontrolled severe asthma in Asia. This study aimed to plug the knowledge gap in this area. MATERIALS AND METHODS: Consecutive patients with asthma managed in our respiratory specialist clinic were evaluated prospectively. Healthcare utilisation comprising unscheduled asthma-related primary care visits, emergency department (ED) visits and hospital admissions were obtained from the national health records system. We defined uncontrolled severe asthma as poor symptom control (Asthma Control Test score <20); 2 or more asthma exacerbations requiring ≥3 days of systemic corticosteroids in the previous year; 1 or more serious asthma exacerbation requiring hospitalisation in the previous year; or airflow limitation with pre-bronchodilator forced expiratory volume in 1 second (FEV1) <80% predicted despite high dose inhaled corticosteroids and another controller medication. RESULTS: Of the 423 study participants, 49 (11.6%) had uncontrolled severe asthma. Compared to non-severe asthma, patients with uncontrolled severe asthma were older and more likely to be female and obese. They had a median of 2 (interquartile range: 0 to 3) exacerbations a year, with 51% having ≥2 exacerbations in the past 12 months. They were responsible for 43.9% of the hospital admissions experienced by the whole study cohort. Mean annual direct asthma costs per patient was S$2952 ± S$4225 in uncontrolled severe asthma vs S$841 ± S$815 in non-severe asthma. CONCLUSION: Approximately 12% of patients with asthma managed in a hospital-based respiratory specialist clinic in Singapore have uncontrolled severe asthma. They account for a disproportionate amount of healthcare utilisation and costs. Healthcare strategies targeting these patients are urgently needed.

Obstructive sleep apnoea and Type 2 diabetes mellitus: are they connected?

Obstructive sleep apnoea (OSA), a sleep-related breathing condition, is diagnosed based on a patient's apnoea-hypopnea index from a sleep study, and the presence or absence of symptoms. Diabetes mellitus (DM) and OSA share a significant common risk factor, obesity, with all three conditions contributing to the risk of developing cardiovascular diseases. The pathophysiological links between OSA and DM are still unclear, but intermittent hypoxia may be an important mechanism. More awareness of the possible link between OSA and DM is needed, given their increasing prevalence locally and worldwide. Continuous positive airway pressure is the standard treatment for OSA, while weight loss through dietary and lifestyle modifications is important to holistically manage patients with either condition. There is currently insufficient evidence to support the benefits of screening every diabetic patient for OSA. However, diabetic patients with symptoms suggestive of OSA should be referred to a sleep specialist for further evaluation.