Effect of an Interdisciplinary Weight Loss and Lifestyle Intervention on Obstructive Sleep Apnea Severity

Key Points Question Is an interdisciplinary weight loss and lifestyle intervention combined with usual care (continuous positive airway pressure [CPAP] therapy) effective for the treatment of moderate to severe obstructive sleep apnea (OSA) in men with overweight or obesity? Findings In this randomized clinical trial involving 89 Spanish men with moderate to severe OSA who had overweight or obesity and were receiving CPAP therapy, an 8-week interdisciplinary weight loss and lifestyle intervention significantly improved OSA severity and other outcomes compared with usual care alone. At 8 weeks, 45% of participants in the intervention group no longer required CPAP therapy; at 6 months, 62% of participants in the intervention group no longer required CPAP therapy. Meaning This study’s findings suggest that this weight loss and lifestyle intervention might be considered as a central strategy to address OSA and comorbidities.

0.718•loge (γ-GT) + 0.053•Waist Circumference -15.745)) / ((1 + e 0.953•loge (Triglycerides) + 0.139•BMI + 0.718•loge (γ-GT) + 0.053•Waist Circumference -15.745)) •100. 23 Changes in systolic blood pressure (mm Hg), diastolic blood pressure (mm Hg) and mean blood pressure (mm Hg) were also considered as cardiometabolic risk endpoints. Blood pressure was measured with an ambulatory blood pressure monitor (Omron M3 Blood Pressure Monitor, OMRON Healthcare, Hoofddorp, Netherlands) in a sitting position after at least five min of rest. The mean of two measurements was recorded. Mean blood pressure was calculated at each reading as one third of systolic pressure plus two thirds of diastolic pressure.

Additional Health-Related Quality of Life and Lifestyle Habits Endpoints
Additional endpoints included health-related quality of life and lifestyle habits. Health-related quality of life scores were obtained through the Sleep Apnea Quality of Life (SAQLI) 24 and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). 25,26 SAQLI is a 35 item self-report instrument assessing OSA specific quality of life through four core domains: daily functioning, social interactions, emotional functioning, and symptoms. The total score (average of the four components, 1 to 7) ranges from 1 to 7, with higher scores indicating better health-related quality of life. 24 SF-36 is also a widely used self-report measure of quality of life composed by eight scaled scores (vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health). Final physical and mental component summaries scores range from 0 to 100, with higher scores indicating better health-related quality of life with respect to either the physical or mental component. 25,26 The Food Behavior Checklist (FBC) 27 was used to assess participants' food intake and habits. FBC comprises seven subscales including consumption of fruit and vegetables (9 items), diet quality (4 items), fast food (3 items), dairy/calcium (2 items), sweetened beverages (2 items), meat (1 item) and food security (1 item). A total FBC score was calculated as the sum of these subscales ranging from 22 to 81, with higher scores indicating healthier dietary pattern. 27 Physical activity was measured using daily step/km logs recorded by participants with a spring-levered pedometer. Participants were required to wear the pedometer all day and register the number of step/km achieved per day in a seven-day step log. The average step/km per day was then calculated at baseline and follow-ups. Regarding the remaining lifestyle habits, smoking and alcohol intake were measured at baseline and follow-ups using seven-day self-reported tobacco and alcohol eMethods 3. Weight Loss and Lifestyle Intervention The design and implementation of the INTERAPNEA weight loss and lifestyle intervention was based on results of previous research 6,28 and the most recent international evidenced-based clinical practice guidelines for the management of obesity and OSA. [29][30][31] The intervention lasted eight weeks and was composed of five different modules: nutritional behavior change, moderate aerobic exercise, smoking reduction and cessation, alcohol intake avoidance, and sleep hygiene. Each component included group-based weekly sessions of 60-90 min lead and supervised by a trained professional in the field (i.e. human nutrition and dietetics, physical activity and sport sciences, clinical psychology, and sleep medicine).
The cornerstone of this intervention was the use of the Transtheoretical Model of Health Behavior Change, 32 a well-recognized biopsychosocial model based on integrating key strategies, processes and principles of behavior change theories into a comprehensive interventional approach for the achievement of sustainable health-related behaviors. 32 The general behavioral change techniques used in each component of the intervention included motivation and preparation for action; goal-setting and action-planning; self-monitoring and functional behavioral analysis; review of behavioral goals, action plans, and adherence ; problem solving and social skills; and self-efficacy, maintenance, and relapse prevention (a detailed description and timing of the INTERAPNEA intervention modules and components, as well as the rationale and specific session topics of each module, has previously been published). 10 Nutritional Behavior Change 10 The nutrition module consisted of eight 60-90-min sessions in a group format addressing dietary patterns using integrated techniques of nutrition education and behavioral change such as goal-setting, cognitive restructuring, stimulus control, progressive muscle relaxation, social skills and assertiveness, and problemsolving skills. The nutrition education was based on the World Health Organization (WHO) latest recommendations on food intake and healthy diet, and each session followed a three-part format: i) Brief The eight-week physical exercise program consisted of weekly 60-min sessions of supervised moderate intensity aerobic exercise (i.e. 55-65% of the heart rate reserve) and individualized goal-setting consisting of increasing daily step/km per week. In the weekly supervised training sessions, participants were required to walk at a moderate intensity for 60 min wearing a heart rate monitor in order to train themselves to walk at that intensity during the week. With respect to goal-setting, they were advised to increase their daily steps/km by 15% per week, based on their daily steps/km logs. Sessions were also based on treating those frequent inadequate sleep habits found in patients with OSA, i.e. sleep restriction, irregular schedule and inappropriate sleep environment.

Smoking Reduction and Cessation 10
Participants who were current smokers and willing to quit were required to attend a weekly 60-90-min session over eight weeks lead by two clinical psychologists. The intervention was based on the group behavior therapy for smoking cessation by Becoña et al., 33 which seeks the progressive reduction of tobacco consumption through the use of nicotine and cigarette fading, 34 and behavior change techniques such as information on smoking, self-monitoring, stimulus control, avoidance of withdrawal symptoms, and relapse prevention.
Nicotine and cigarette fading has been shown to be the most effective method to reduce and stop smoking with abstinence rates of 86% at the end of treatment and nearly 60% at a 12 month follow-up. 35 Participants were mainly required to keep a daily record of number of cigarettes smoked and triggers for smoking (self-monitoring), change the type of cigarette smoked to a lesser nicotine content brand each week (30%, 60% and 90% nicotine reductions from baseline), reduce the number of cigarettes smoked by 30% (motivation), muscle and cognitive relaxation techniques to address withdrawal symptoms, and identification of high-risk situations for smoking and problem-solving skills (relapse prevention) were used.

Alcohol Intake Avoidance 10
The INTERAPNEA alcohol intake reduction and avoidance module lasted eight weeks comprising fortnightly sessions of 60 min supervised by two clinical psychologists. Similar to the smoking reduction and cessation module, progressive reduction of alcohol intake in those participants with no alcohol addiction but excessive consumption was pursued. Participants were indicated to reduce the number of units of alcohol consumed per day/week by 30% each week, keeping a log of alcohol-consumption per day including units of alcohol consumed and triggers of consumption. During the sessions, participants received detailed information of alcohol general and specific to OSA health-related consequences. Furthermore, behavior change techniques such as stimulus control, muscle and cognitive relaxation and problem -solving skills related to alcohol consumption were used. eMethods 4. Assessment of Adherence and Integrity of Intervention and Intervention Adherence

Assessment of Adherence and Integrity of Intervention 10
Integrity of the intervention and treatment fidelity was evaluated and ensured through the design and implementation of different strategies of process assessment, monitoring and enhancement in order to guarantee internal and external validity of the trial. 36 Regarding the study design and provider of intervention training, we developed a comprehensive hand-book for the qualified INTERAPNEA study intervention providers/professionals/training personnel of each module. Each intervention manual identified the theoretical model of the intervention and provided detailed descriptions of session objectives, treatment guidelines in accordance with each objective (i.e., contents, tasks and activities, recommendations, and timing), participant's homework, and material needed for each session. We also provided each participant with an adapted patienthandbook for each intervention component including descriptions of sessions, and work and logging sheets.
Furthermore, we ensured fidelity in the treatment delivery, receipt, and enactment through the use of these intervention protocols/manuals and monitoring of the implementation. Regarding the treatment delivery, the standardization of the intervention supported the protocol adherence of providers and the treatment differentiation (i.e., the delivery of the target treatment and no other). Similarly, we included a check-list for provider's self-report concerning the achievement of session objectives. With respect to the treatment receipt and enactment, fidelity was assessed and confirmed through different strategies such as the structuring of the intervention around achievement-based objectives, collecting and reviewing of participants self -monitored data (daily step/km log, sleep diaries, alcohol and tobacco consumption records), and information delivery in different formats (e.g., written in the handbooks, and verbal and visual in the sessions).
Apart from the above mention strategies, we also considered complementary approaches in order to reduce participant drop-out rates and increase adherence, such as prevention of commitments or vacation periods, use of well-equipped and conditioned facilities, and supervision by a qualified and certified pair of pro viders in each session, motivating and supporting participants. Participants' attendance to each intervention session was recorded by providers and causes of absence were recorded through phone-calls.

Intervention Adherence
Most participants in the intervention group attended all sessions of each intervention component (i.e. nutritional behavior change, physical exercise, sleep hygiene, smoking cessation and alcohol avoidance). Of  Abbreviations: CI, confidence interval; SpO2, oxygen saturation; AHI, apnea-hypopnea index; REM, rapid eye movement; NREM, non-rapid eye movement. a Using the group × visit interaction term from a linear mixed-effects model including study group, time (baseline, 8 weeks and 6 months), and study group × time as fixed effects and participant as random effects. b P < 0.05 from the time × study group interactions. c P < 0.01 from the time × study group interactions. d P < 0.001 from the time × study group interactions. e Pittsburgh Sleep Quality Index scores range from 0 to 21, with higher scores indicating worse sleep quality. f Epworth Sleepiness Scale scores range from 0 to 24, with higher scores indicating more daytime sleepiness.  IR, homeostasis model assessment of insulin resistance; HDL-C, highdensity lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; AST, aspartate aminotransferase; ALT, alanine aminotransferase;γ-GT, γ-glutamyltransferase. SI conversion factors: To convert glucose to millimoles per liter, multiply by 0.05551. To convert insulin to picomoles per liter, multiply by 6.945. To convert total, high-density lipoprotein, and low-density lipoprotein cholesterol to millimoles per liter, multiply by 0.02586. To convert triglycerides to millimoles per liter, multiply by 0.01129. To convert apolipoprotein A1 and B to gram per liter, multiply by 0.01. To convert aspartate aminotransferase to micro-katal per liter, multiply by 0.017. To convert aspartate aminotransferase and γ-glutamyltransferas e to micro-katal per liter, multiply by 0.017. a Using the group × visit interaction term from a linear mixed-effects model including study group, time (baseline, 8 weeks and 6 months), and study group × time as fixed effects and participant as random effects. b P < 0.05 from the time × study group interactions. c P < 0.01 from the time × study group interactions. d P < 0.001 from the time × study group interactions.