Early‐to‐Midlife Body Mass Index Trajectories and Obstructive Sleep Apnoea Risk 10 Years Later

Cho T., Yan E., Chung F.

Although the STOP-Bang questionnaire has been validated for its efficacy and diagnostic performance in various settings, there is no review that summarizes the pertinent evidence of the STOP-Bang questionnaire in the different populations. We aimed to review the evidence of the diagnostic performance of the STOP-Bang questionnaire, correlation between STOP-Bang scores and the probability of obstructive sleep apnea (OSA), and its clinical application in various populations.

Qian Y., Dharmage S.C., Hamilton G.S., Lodge C.J., Lowe A.J., Zhang J., Bowatte G., Perret J.L., Senaratna C.V.

Despite substantial disease burden, existing evidence on the risk factors for obstructive sleep apnea (OSA) have been derived primarily from cross-sectional studies without determining temporality. Therefore, we aimed to systematically synthesize the literature on longitudinal risk factors for sleep study-assessed OSA and questionnaire-assessed probable OSA from cohort studies in the general adult population settings. We systematically searched Embase and Medline (on OVID) databases. Eleven studies met the inclusion criteria. Meta-analyses were not conducted due to methodological heterogeneity of exposure and outcome measurements. There was consistent evidence that weight gain was associated with incident (n = 2) and greater severity (n = 2) of OSA. One study each observed an association of higher baseline body-mass index, male sex, asthma, a specific genetic polymorphism in rs12415421, and insulin resistance/hyperglycemia, with incident OSA. Long-term exposure to ambient air pollution (NO2, n = 1) was associated with OSA, and menopausal transitions (n = 1) with higher apnea-hypopnea index. There were no eligible studies on long-term smoking or alcohol use. In conclusion, approximately 10% increase in weight, especially in males, might alert clinicians to consider potential or worsening OSA. Large, well-designed longitudinal studies are needed to consolidate knowledge on other associations with OSA development, especially on potentially modifiable risk factors.

Senaratna C.V., Lowe A., Walters E.H., Abramson M.J., Bui D., Lodge C., Erbas B., Burgess J., Perret J.L., Hamilton G.S., Dharmage S.C.

AbstractBackground and ObjectiveEarly‐life risk factors for obstructive sleep apnoea (OSA) are poorly described, yet this knowledge may be critical to inform preventive strategies. We conducted the first study to investigate the association between early‐life risk factors and OSA in middle‐aged adults.MethodsData were from population‐based Tasmanian Longitudinal Health Study cohort (n = 3550) followed from 1st to 6th decades of life. Potentially relevant childhood exposures were available from a parent‐completed survey at age 7‐years, along with previously characterized risk factor profiles. Information on the primary outcome, probable OSA (based on a STOP‐Bang questionnaire cut‐off ≥5), were collected when participants were 53 years old. Associations were examined using logistic regression adjusting for potential confounders. Analyses were repeated using the Berlin questionnaire.ResultsMaternal asthma (OR = 1.5; 95% CI 1.1–2.0), maternal smoking (OR = 1.2; 1.05, 1.5), childhood pleurisy/pneumonia (OR = 1.3; 1.04, 1.7) and frequent bronchitis (OR = 1.2; 1.01, 1.5) were associated with probable OSA. The risk‐factor profiles of ‘parental smoking’ and ‘frequent asthma and bronchitis’ were also associated with probable OSA (OR = 1.3; 1.01, 1.6 and OR = 1.3; 1.01–1.9, respectively). Similar associations were found for Berlin questionnaire‐defined OSA.ConclusionsWe found novel temporal associations of maternal asthma, parental smoking and frequent lower respiratory tract infections before the age of 7 years with adult OSA. While determination of their pathophysiological and any causal pathways require further research, these may be useful to flag the risk of OSA within clinical practice and create awareness and vigilance among at‐risk groups.

Ma B., Li Y., Wang X., Du L., Wang S., Ma H., Zhou D., Usman T., Lu L., Qu S.

PurposeFactors related to the occurrence of obstructive sleep apnea syndrome (OSAS) in obesity have not been fully clarified. The aim of this study was to identify the association between OSAS and abdominal fat distribution in a cohort of Chinese obese patients.MethodsThis cross-sectional study collected demographic data of 122 obese patients who were admitted into the in-patient unit of the Department of Endocrinology, Shanghai Tenth People’s Hospital from July 2018 to January 2021. OSAS was diagnosed based on the results of overnight polysomnography, and the abdominal fat distribution was measured by bioelectrical impedance analysis (BIA). Univariate and multivariate logistic regression analyses were used to investigate the association between OSAS and the distribution of abdominal fat.Results(1) The mean age (SD) of the obese patients included was 32.44 (11.81) years old, and the overall incidence rate of OSAS was 51.06%. Twenty-four (25.53%) patients had mild OSAS, 10 (10.64%) had moderate OSAS, and 14 (14.89%) had severe OSAS. The apnea hypopnea index (AHI) of men was significantly higher than that of women (5.50, interquartile range (IQR) 3.80–30.6 vs. 4.2, IQR 1.4–12 events/h, p = 0.014). Meanwhile, men had a significantly higher visceral fat area when compared with women (180.29 ± 51.64 vs. 143.88 ± 53.42 cm2, p = 0.002). (2) Patients with OSAS had a significantly higher waist circumference, fasting plasma glucose, 2 h postprandial plasma glucose, glycated hemoglobin, and visceral fat area than patients without OSAS (all p < 0.05). (3) AHI was significantly positively associated with BMI, neck circumference, waist circumference, and visceral fat area (r = 0.306, p = 0.003; r = 0.380, p < 0.001; r = 0.328, p = 0.002; r = 0.420, p < 0.001) but not with subcutaneous fat area (p = 0.094). Multivariate analysis demonstrated that abdominal fat area and fasting plasma glucose were independent risk factors for OSAS (odds ratio, 1.016; 95% confidence interval, 1.005–1,026, p = 0.005; odds ratio, 1.618; 95% confidence interval, 1.149–2.278, p = 0.006).ConclusionsIn obese patients, the abdominal visceral adipose deposit but not the subcutaneous fat area was associated with OSAS and was an independent risk factor for OSAS. Therefore, improving the distribution of abdominal fat may contribute to alleviating the severity of OSAS in obesity.

Ali G.B., Lowe A.J., Perret J.L., Walters E.H., Lodge C.J., Johns D., James A., Erbas B., Hamilton G.S., Bowatte G., Wood-Baker R., Abramson M.J., Bui D.S., Dharmage S.C.

BackgroundHigh body mass index (BMI) trajectories from childhood to adulthood are associated with the development of some chronic diseases, but whether such trajectories influence adult asthma has not been investigated to date. Therefore, we investigated associations between BMI trajectories from childhood to middle age (5–43 years) and incidence, persistence and relapse of asthma from ages 43 to 53 years.MethodsIn the Tasmanian Longitudinal Health Study (n=4194), weight and height were recorded at eight time-points between 5 and 43 years of age. BMI trajectories were developed using group-based trajectory modelling. Associations between BMI trajectories and asthma incidence, persistence and relapse from age 43 to 53 years, bronchial hyperresponsiveness (BHR) at age 50 years, and bronchodilator responsiveness at age 53 years were modelled using multiple logistic and linear regression.ResultsFive distinct BMI trajectories were identified: average, low, child high-decreasing, child average-increasing and high. Compared with the average trajectory, child average-increasing and high trajectories were associated with increased risk of incident asthma (OR 2.6, 95% CI 1.1–6.6 and OR 4.4, 95% CI 1.7–11.4, respectively) and BHR in middle age (OR 2.9, 95% CI 1.1–7.5 and OR 3.5, 95% CI 1.1–11.4, respectively). No associations were observed for asthma persistence or relapse.ConclusionsParticipants with child average-increasing and high BMI trajectories from childhood to middle age were at higher risk of incident adult asthma. Thus, encouraging individuals to maintain a normal BMI over the life course may help reduce the burden of adult asthma.

Oktay Arslan B., Ucar Hosgor Z.Z., Orman M.N.

St-Onge M., Tasali E.

Dong Z., Xu X., Wang C., Cartledge S., Maddison R., Shariful Islam S.M.

Background Research evidence suggests a close relationship between overweight and obesity with obstructive sleep apnoea (OSA); however, the extent of this relationship among different population groups is relatively unknown. The aim of this paper was to conduct a systematic review and meta-analysis to determine the magnitude of association of overweight and obesity with OSA in different population groups. Methods We searched five electronic databases (Medline, Embase, Cochrane Library, CBM and CNKI) from inception to December 2017 for comparative epidemiological studies assessing the relation between overweight and obesity with OSA. Studies were included if they reported OSA by polysomnography and overweight/obesity by body mass index. Two authors independently screened titles and abstracts, selected studies and extracted data. Study quality was assessed using the Newcastle-Ottawa Scale. Random effects meta-analysis was used to estimate pooled effect sizes with 95% confidence intervals (CI). Heterogeneity was examined using Cochrane's Q statistic and I2 test and explored using subgroup analyses for adults and children, adjusting for potential confounders. Publication bias was assessed using a funnel plot. Results Twelve case-control studies encompassing a total of 3214 participants (Obese group n = 773, Non-Obese group n = 315; OSA group n = 1742, Non-OSA group n = 384) were analyzed. Results showed that increased body mass index was associated with higher risk of OSA in the adult group. The Obese group was associated with increased risk of apnoea-hypopnoea index (AHI) compared to the Non-Obese group and the differences were statistically significant in both children (Mean Difference = 12.29; 95% CI 8.46–16.11; P  Conclusions These findings suggest that overweight and obesity are important risk factors for OSA in both adults and children. Future studies are required to determine the effects of weight loss interventions in the development of obesity-related OSA.

Wang S.H., Keenan B.T., Wiemken A., Zang Y., Staley B., Sarwer D.B., Torigian D.A., Williams N., Pack A.I., Schwab R.J.

Rationale: Obesity is the primary risk factor for obstructive sleep apnea (OSA). Tongue fat is increased in obese persons with OSA, and may explain the relationship between obesity and OSA. Weight loss improves OSA, but the mechanism is unknown.Objectives: To determine the effect of weight loss on upper airway anatomy in subjects with obesity and OSA. We hypothesized that weight loss would decrease soft tissue volumes and tongue fat, and that these changes would correlate with reductions in apnea-hypopnea index (AHI).Methods: A total of 67 individuals with obesity and OSA (AHI ≥ 10 events/h) underwent a sleep study and upper airway and abdominal magnetic resonance imaging before and after a weight loss intervention (intensive lifestyle modification or bariatric surgery). Airway sizes and soft tissue, tongue fat, and abdominal fat volumes were quantified. Associations between weight loss and changes in these structures, and relationships to AHI changes, were examined.Measurements and Main Results: Weight loss was significantly associated with reductions in tongue fat and pterygoid and total lateral wall volumes. Reductions in tongue fat were strongly correlated with reductions in AHI (Pearson's rho = 0.62, P < 0.0001); results remained after controlling for weight loss (Pearson's rho = 0.36, P = 0.014). Reduction in tongue fat volume was the primary upper airway mediator of the relationship between weight loss and AHI improvement.Conclusions: Weight loss reduced volumes of several upper airway soft tissues in subjects with obesity and OSA. Improved AHI with weight loss was mediated by reductions in tongue fat. New treatments that reduce tongue fat should be considered for patients with OSA.

Benjafield A.V., Ayas N.T., Eastwood P.R., Heinzer R., Ip M.S., Morrell M.J., Nunez C.M., Patel S.R., Penzel T., Pépin J., Peppard P.E., Sinha S., Tufik S., Valentine K., Malhotra A.

There is a scarcity of published data on the global prevalence of obstructive sleep apnoea, a disorder associated with major neurocognitive and cardiovascular sequelae. We used publicly available data and contacted key opinion leaders to estimate the global prevalence of obstructive sleep apnoea.We searched PubMed and Embase to identify published studies reporting the prevalence of obstructive sleep apnoea based on objective testing methods. A conversion algorithm was created for studies that did not use the American Academy of Sleep Medicine (AASM) 2012 scoring criteria to identify obstructive sleep apnoea, allowing determination of an equivalent apnoea-hypopnoea index (AHI) for publications that used different criteria. The presence of symptoms was not specifically analysed because of scarce information about symptoms in the reference studies and population data. Prevalence estimates for obstructive sleep apnoea across studies using different diagnostic criteria were standardised with a newly developed algorithm. Countries without obstructive sleep apnoea prevalence data were matched to a similar country with available prevalence data; population similarity was based on the population body-mass index, race, and geographical proximity. The primary outcome was prevalence of obstructive sleep apnoea based on AASM 2012 diagnostic criteria in individuals aged 30-69 years (as this age group generally had available data in the published studies and related to information from the UN for all countries).Reliable prevalence data for obstructive sleep apnoea were available for 16 countries, from 17 studies. Using AASM 2012 diagnostic criteria and AHI threshold values of five or more events per h and 15 or more events per h, we estimated that 936 million (95% CI 903-970) adults aged 30-69 years (men and women) have mild to severe obstructive sleep apnoea and 425 million (399-450) adults aged 30-69 years have moderate to severe obstructive sleep apnoea globally. The number of affected individuals was highest in China, followed by the USA, Brazil, and India.To our knowledge, this is the first study to report global prevalence of obstructive sleep apnoea; with almost 1 billion people affected, and with prevalence exceeding 50% in some countries, effective diagnostic and treatment strategies are needed to minimise the negative health impacts and to maximise cost-effectiveness.ResMed.

Chan K.C., Au C.T., Hui L.L., Ng S., Wing Y.K., Li A.M.

Understanding the natural history of childhood OSA can help to determine disease prognosis and to guide risk stratification and management strategies.To evaluate the natural history of childhood OSA and factors associated with spontaneous remission and persistent and incident OSA from childhood to late adolescence/early adulthood, a longitudinal analysis of a prospective community-based cohort was designed. Subjects from a cohort established for an OSA prevalence study were invited to participate in this 10-year follow-up study.Two hundred and forty-three participants (59% male) took part, and their mean age was 9.8 (SD, ± 1.8) and 20.2 (SD, ± 1.9) years at baseline and follow-up, respectively. The mean follow-up duration was 10.4 (SD, ± 1.1) years. Associations between baseline and follow-up log-transformed obstructive apnea-hypopnea index (OAHI) differed by age; a significant positive association was observed only among participants aged 10 years or older at baseline. Overall polysomnographic remission rate (with OAHI < 1 event/h at follow-up) of childhood OSA was 30%, and 69% had an OAHI < 5 events/h at follow-up. Complete remission of OSA was associated with female sex. Incidence of adolescent/adult OSA with an OAHI ≥ 5 events/h at follow-up was 22%. Male sex and higher baseline BMI z score were associated with incident OSA.A proportion of children with OSA, particularly female children, had complete resolution during transition to late adolescence or early adulthood. Childhood and adolescent OSA are distinct entities, with the latter more likely to persist into adulthood. Obesity and male sex are consistent key risk factors for incident OSA.

Senaratna C.V., Perret J.L., Lowe A., Bowatte G., Abramson M.J., Thompson B., Lodge C., Russell M., Hamilton G.S., Dharmage S.C.

Hamilton G.S., Chai-Coetzer C.L.

Senaratna C.V., Lowe A., Perret J.L., Lodge C., Bowatte G., Abramson M.J., Thompson B.R., Hamilton G., Dharmage S.C.

The concordance of different indices from type-4 sleep studies in diagnosing and categorising the severity of obstructive sleep apnoea is not known. This is a critical gap as type-4 sleep studies are used to diagnose obstructive sleep apnoea in some settings. Therefore, we aimed to determine the concordance between flow-based apnoea-hypopnoea index (AHIflow50% ) and oxygen desaturation index (ODI3% ) by measuring them concurrently. Using a random sub-sample of 296 from a population-based cohort who underwent two-channel type-4 sleep studies, we assessed the concordance between AHIflow50% and ODI3% . We compared the prevalence of obstructive sleep apnoea of various severities as identified by the two methods, and determined their concordance using coefficient Kappa(κ). Participants were aged (mean ± SD) 53 ± 0.9 years (48% male). The body mass index was 28.8 ± 5.2 kg m-2 and neck circumference was 37.4 ± 3.9 cm. The median AHIflow50% was 5 (inter-quartile range 2, 10) and median ODI3% was 9 (inter-quartile range 4, 15). The obstructive sleep apnoea prevalence reported using AHIflow50% was significantly lower than that reported using ODI3% at all severity thresholds. Although 90% of those with moderate-severe obstructive sleep apnoea classified using AHIflow50% were identified by using ODI3% , only 46% of those with moderate-severe obstructive sleep apnoea classified using ODI3% were identified by AHIflow50% . The overall concordance between AHIflow50% and ODI3% in diagnosing and classifying the severity of obstructive sleep apnoea was only fair (κ = 0.32), better for males (κ = 0.42 [95% confidence interval 0.32-0.57] versus 0.22 [95% confidence interval 0.09-0.31]), and lowest for those with a body mass index ≥ 35 (κ = 0.11). In conclusion, ODI3% and AHIflow50% from type-4 sleep studies are at least moderately discordant. Until further evidence is available, the use of ODI3% as the measure of choice for type-4 sleep studies is recommended cautiously.

Harel O., Mitchell E.M., Perkins N.J., Cole S.R., Tchetgen Tchetgen E.J., Sun B., Schisterman E.F.

Epidemiologic studies are frequently susceptible to missing information. Omitting observations with missing variables remains a common strategy in epidemiologic studies, yet this simple approach can often severely bias parameter estimates of interest if the values are not missing completely at random. Even when missingness is completely random, complete-case analysis can reduce the efficiency of estimated parameters, because large amounts of available data are simply tossed out with the incomplete observations. Alternative methods for mitigating the influence of missing information, such as multiple imputation, are becoming an increasing popular strategy in order to retain all available information, reduce potential bias, and improve efficiency in parameter estimation. In this paper, we describe the theoretical underpinnings of multiple imputation, and we illustrate application of this method as part of a collaborative challenge to assess the performance of various techniques for dealing with missing data (Am J Epidemiol. 2018;187(3):568-575). We detail the steps necessary to perform multiple imputation on a subset of data from the Collaborative Perinatal Project (1959-1974), where the goal is to estimate the odds of spontaneous abortion associated with smoking during pregnancy.

Shah N.M., Suh E.