# Association of positive airway pressure adherence with use of antihypertensive drugs in patients with sleep apnoea

Dany Jaffuel, Erika Nogue, François Roubille, Jean-Pierre Mallet, Sébastien Bailly, François Goupil, Audrey Thomas, Carole Hervé, Philippe Masson, Acya Bizieux-Thaminy, et al.

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## To cite this version:

Dany Jaffuel, Erika Nogue, François Roubille, Jean-Pierre Mallet, Sébastien Bailly, et al. "Association of positive airway pressure adherence with use of antihypertensive drugs in patients with sleep apnoea." ERJ Open Research, 2025, 11 (4), pp.00081-2025. 10.1183/23120541.00081-2025. hal-05040879

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Distributed under a Creative Commons CC BY 4.0 - Attribution - International License
Association of positive airway pressure adherence with use
of antihypertensive drugs in patients with sleep apnoea

Dany Jaffuel ¹ ², Erika Nogue ³, François Roubille ² ⁴, Jean-Pierre Mallet ¹ ², Sébastien Bailly ⁵, François Goupil ⁶, Audrey Thomas ⁷, Carole Hervé ⁸, Philippe Masson ⁹, Acya Bizieux-Thaminy ¹⁰, Margaux Blanchard ¹¹, Sandrine Kerbrat ¹², Abdelkebir Sabil ¹³ ¹⁴, Wojciech Trzepizur ¹⁵ ¹⁶, Camille Roubille ² ¹⁷, Sarah Skinner ¹⁸, Arnaud Bourdin ¹ ², Nicolas Molinari ¹⁹, Frédéric Gagnadoux ¹⁵ ¹⁶

¹ Department of Pneumology, Arnaud de Villeneuve, Regional University Hospital of Montpellier, Montpellier, France.

² PhyMedExp, University of Montpellier, INSERM U1046, CNRS UMR 9214, Montpellier, France.

³ Clinical Research and Epidemiology Unit, CHU Montpellier, Univ Montpellier, Montpellier, France.

⁴ Department of Cardiology, Arnaud de Villeneuve, Regional University Hospital of Montpellier, Montpellier, France.

⁵ University Grenoble Alpes, Inserm, CHU Grenoble Alpes, HP2, Grenoble, France.

⁶ Department of Respiratory Diseases, Le Mans General Hospital, Le Mans, France.

⁷ Respiratory Unit, Pôle Santé des Olonnes, Olonne sur Mer, France.

⁸ Department of Physiology and Sleep Medicine, Nantes University Hospital, Nantes, France.

⁹ Department of Respiratory Diseases, Cholet General Hospital, Cholet, France.

¹⁰ Department of Respiratory Diseases, La Roche sur Yon General Hospital, La Roche sur Yon, France.

¹¹ MBL Consult, Angers, France.

¹² DAMAD, Plouzane, France.

¹³ Pays de la Loire Respiratory Health Research Institute, Beaucouzé, France.

¹⁴ Cloud Sleep Lab, Paris, France.

¹⁵ Department of Respiratory and Sleep Medicine, Angers University Hospital, Angers, France.

¹⁶ INSERM, CNRS, MITOVASC, Equipe CarME, SFR ICAT, University of Angers, Angers, France.
<footnote n="17">17 Department of Internal Medicine, Lapeyronie Hospital, Regional University Hospital of Montpellier, Montpellier, France.</footnote>

<footnote n="18">18 Regional University Hospital of Montpellier, Montpellier, France.</footnote>

<footnote n="19">19 IDESP, INSERM, PreMEDical INRIA, Univ Montpellier, CHU Montpellier, Montpellier, France.</footnote>
Abstract

**Background:**

The impact of positive airway pressure (PAP) therapy on the use of oral antihypertensive drugs (OAHDs) in patients with obstructive sleep apnoea (OSA) remains unclear. This study aimed to evaluate the association between PAP use and the delivery of OAHDs.

**Methods:**

Data from the Pays de la Loire Sleep Cohort were linked with the French health insurance database to quantify OAHD delivery in patients with hypertension at the initiation of PAP therapy. The primary end-point was the change in OAHD score, reflecting the number of OAHD classes delivered. PAP use groups were defined as: termination, $0-<4 \text{ h}\cdot\text{day}^{-1}$, $4-<6 \text{ h}\cdot\text{day}^{-1}$ and $\ge 6 \text{ h}\cdot\text{day}^{-1}$.

**Results:**

The study included 2205 OSA patients (median (Q1-Q3) apnoea-hypopnea index of 39 (30-55) events·h⁻¹), of whom 68% were male. The median age was 61 (54-68) years, the body mass index (BMI) was 32.42 (28.95-36.43) kg·m⁻² and the Epworth score was 10 (6-13). After 1 year of PAP, the mean±sd OAHD score decreased from 2.16±1.11 to 2.13±1.18 with no significant difference between PAP use groups. Respectively, 11.93% and 11.07% of patients experienced a decrease or increase in OAHD score, with no significant difference between PAP use groups. Multivariate analysis revealed that an increase in OAHD score was significantly positively associated with age, usage of calcium channel blockers and number of consultations. A decrease in OAHD score was significantly associated with baseline OAHD score, number of consultations, use of loop diuretics and a decrease in medication possession ratio.

**Conclusion:**

PAP use is not associated with a change in OAHD score after 1 year.
Introduction

Since the 1990s, obstructive sleep apnoea (OSA) has been recognised as a secondary cause of hypertension [1], with a prevalence ranging from 25% to 80% among hypertensive patients, depending on the severity of OSA and hypertension [2–5]. Given this strong association, various guidelines recommend screening for OSA in patients with hypertension. However, there is no clear recommendation regarding the role of OSA treatment in the management of hypertension in patients with OSA [2, 4–6].

Numerous studies have explored the impact of positive airway pressure (PAP) therapy on blood pressure (BP) [7]. In PAP-treated OSA patients with hypertension, meta-analyses of randomised controlled trials (RCTs) have demonstrated clinically significant reductions in both nocturnal, diurnal and 24-h systolic and diastolic BP [8–10]. Similar results were obtained in patients with resistant hypertension, whereas PAP use did not reduce BP in normotensive adults with OSA [8, 11]. Overall, these meta-analyses suggest that PAP use reduces BP in adults with OSA and hypertension, but the quality of evidence was considered modest [9] or moderate due to imprecision [8]. Importantly, stratified analyses from one of these meta-analyses suggest a dose effect of PAP use on BP [9], a finding that concurs with other meta-analyses [12, 13]. However, exploratory analyses of RCTs with at least 24–26 weeks of PAP show a possible loss of efficacy over time [9]. Hypertension management includes both lifestyle modifications and pharmacological treatments, with lifestyle changes potentially reducing the need for medication [2, 6].

Although current guidelines promote implementing lifestyle interventions, they do not endorse the use of PAP therapy for treating hypertension, due to the unclear impact of PAP therapy on oral antihypertensive drug (OAHD) use. To date, no long-term RCT has studied the OAHD-sparing effect of PAP therapy in hypertensive patients with OSA.

Conducting a long-term RCT comparing PAP therapy to no therapy in symptomatic OSA patients would be neither ethical nor feasible, due to the long-term follow-up and cost. Using real-world observational data provides an alternative approach [14–16] that overcomes problems associated with the RCTs, such as the study duration and the randomisation of PAP therapy [17] for symptomatic patients for whom the benefit of PAP has been demonstrated.

Nevertheless, both randomised and real-life studies present problems of external validity, with randomised studies raising the question in the real world of the representativeness of the included population [16], and real-life studies posing multiple problems of selection biases [14, 18].

Using data from the previously described Pays de la Loire multicentre sleep cohort study [19, 23] we aimed to evaluate the relationship between 1 year of PAP use and the number of OAHDs dispensed to patients with prevalent hypertension at PAP initiation.
# Material and methods

## Study design and population

The study relied on data collected by the multicentre longitudinal "Institut de Recherche en Santé Respiratoire" (IRSR) Pays de la Loire Sleep Cohort study, which were linked with the data from the French administrative healthcare database ("Système National des Données de Santé" (SNDS)). The SNDS contains individualised, anonymous and comprehensive data on healthcare spending reimbursements. The linkage process between the IRSR Pays de la Loire Sleep Cohort and the SNDS database was conducted as previously reported [24].

All patients with newly diagnosed OSA (apnoea-hypopnea index (AHI) ≥5 events·h⁻¹ of sleep (or recording) on in-lab polysomnography (PSG) or type 3 home sleep apnoea testing (HSAT)) between 1 May 2007 and 31 December 2018, who received stable antihypertensive medication 3 months prior to OSA diagnosis and were prescribed PAP therapy for at least 1 year were eligible for the study. Patients who had switched to a mandibular advancement device, had bariatric or maxillofacial surgery, or died during the first year of PAP therapy were excluded from the analysis.

## Ethics

The protocol complied with the Declaration of Helsinki and was reviewed and approved by an independent ethics committee (University of Angers ethics committee, reference number 2009/17), the "Comité Consultatif sur le Traitement de l'Information en matière de Recherche" (reference number 07.207 bis) and the "Commission Nationale Informatique et Liberté" (reference number 908157). All participants had given their written informed consent.

## Descriptive data

Anthropometric data, smoking habits, alcohol consumption, medical history and medication use were collected as previously described [24]. Patients were diagnosed by either HSAT or PSG, according to pre-test clinical probability of OSA [25]. The HSAT and PSG exams were scored manually using recommended criteria [26].

## Outcome variable definitions

### Adherence to PAP therapy

According to the criteria defined by the French national health insurance, PAP therapy was prescribed in patients with severe OSA and in those with mild-to-moderate OSA associated with cardiovascular comorbidities and/or severe daytime sleepiness.

Based on the digital downloads from PAP devices, objective daily PAP use (average number of daily hours of PAP use since the last visit) was collected at each follow-up visit (3 months, 6 months and semi-annually) by the home care provider (ASTEN SANTE, Beaucouzé, France) and documented in the database. Patients were divided into four groups (PAP
termination, PAP use 0-<4 h·day⁻¹, PAP use 4-<6 h·day⁻¹, PAP use ≥6 h·day⁻¹). Subjects in the PAP termination group stopped using PAP therapy during the study period. This was determined from the cohort database and confirmed in the SNDS by checking the permanent cessation of PAP reimbursements.

## Adherence to OAHDs

The medication possession ratios (MPRs) of OAHDs were measured using the SNDS database for the 3-month period prior to PAP initiation and annually after PAP initiation. The MPR corresponds to the number of days of treatment delivered divided by the number of days of follow-up [27]. Patients with an MPR ≥80% were considered treatment adherent and those with MPR <80% were considered nonadherent.

## OAHDs

Prescribed OAHDs are listed in the online data supplement (see table 1). OAHD classes included angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, dihydropyridine calcium channel blockers, nondihydropyridine calcium channel blockers, loop diuretics, potassium sparing diuretics, aldosterone antagonist diuretics, thiazide or thiazide-type diuretics, cardioselective beta blockers, cardioselective and vasodilatory beta blockers, noncardioselective beta blockers, intrinsic sympathomimetic activity beta blockers, combined alpha and beta-receptor beta blockers, direct renin inhibitor, alpha-1 blockers, central alpha2-agonist and other centrally acting drugs, and direct vasodilators. The OAHD groups were renin-angiotensin system (RAS) blockers, calcium channel blockers, loop diuretics, thiazide or thiazide-type diuretics, diuretics-aldosterone antagonists or diuretics potassium sparing, beta-blockers, others.

## OAHD score

The OAHD score was the primary end-point of the study and was defined as the number of OAHD classes the patient simultaneously received for at least 30 days. Each patient was assigned an OAHD score when they initiated PAP therapy. Their score was then re-evaluated at each time-point. The OAHD score was increased by one point if a new OAHD class was introduced and was decreased by one point if an OAHD class was discontinued. Single-pill combinations were analysed as per their constituent classes. For example, if the combination included two OAHD classes, the OAHD score would be two. Patients were then divided into the following three groups according to the evolution of their OAHD score: decreased OAHD score, stable OAHD score or increased OAHD score.

## Statistical analysis

Continuous data were expressed as means and standard deviations or medians and interquartile range (Q1-Q3). Qualitative parameters were expressed as numbers and percentages. Group comparisons were performed using ANOVA or Kruskal-Wallis tests for quantitative data. Qualitative variables were compared using Chi2 or Fisher exact tests. When
the overall comparison was significant, the groups were compared two by two using the Holm correction for multiple testing.

A generalised logit model was used to study the impact of the PAP use on the OAHD evolution group at 1 year. The modality "stable" was chosen as the reference category. Univariate analysis was presented after adjustment for the number of OAHD at PAP initiation. A multivariate analysis was performed on all clinically relevant variables and variables with p<0.20 in univariate analysis. A backward selection procedure was applied; only variables with a p<0.05 remained in the final model. Odds ratios were reported with their 95% confidence intervals. A bilateral p-value of <0.05 was considered statistically significant. Missing data were not replaced. All analyses were conducted by the Clinical Research and Epidemiology Unit at the Montpellier University Hospitals using SAS (Enterprise Guide, version 9.04; SAS Institute, Cary, NC, USA) and R (version 4.3.2, R Foundation for Statistical Computing, Vienna, Austria).

# Results

## Patient characteristics

Of the 5185 patients who were recruited, data from 2205 patients were ultimately analysed (figure 1). Patients were 68.03% male with a median (Q1–Q3) age of 61 (54–68) years, an initial AHI of 39 (30–55) events·h⁻¹, a body mass index (BMI) of 32.42 (28.95–36.43) kg·m⁻² and an Epworth score of 10 (6–13)] (table 1). Supplemental table 7 depicts the characteristics of included and excluded populations.

<table><caption>TABLE 1 Description of the population at the start of positive airway pressure (PAP) therapy. Patients were divided into four groups (PAP termination, PAP use 0–<4 h·day⁻¹, PAP use 4–<6 h·day⁻¹, PAP use ≥6 h·day⁻¹) related to PAP use at 1 year</caption><thead><tr><th></th><th>n</th><th>Whole population at start of PAP<br>n=2205</th><th>PAP termination<br>n=279</th><th>PAP use 0–<4 h·day⁻¹<br>n=383</th><th>PAP use 4–<6 h·day⁻¹<br>n=562</th><th>PAP use ≥6 h·day⁻¹<br>n=981</th><th>p-value</th></tr></thead><tbody><tr><td>Age</td><td>2205</td><td>61.00 (54.00–68.00)</td><td>63.00 (54.00–69.00)<sup>a</sup></td><td>58.00 (50.00–66.00)<sup>a,b,e</sup></td><td>61.00 (54.00–67.00)<sup>b,c</sup></td><td>63.00 (56.00–70.00)<sup>a,c</sup></td><td>&lt;0.001</td></tr><tr><td>Gender (male)</td><td>2205</td><td>1500 (68.03)</td><td>181 (64.87)</td><td>261 (68.15)</td><td>399 (71.00)</td><td>659 (67.18)</td><td>0.275</td></tr><tr><td>BMI (kg·m⁻²)</td><td>2192</td><td>32.42 (28.95–36.43)</td><td>31.23 (27.77–35.38)<sup>d,e</sup></td><td>33.18 (29.71–36.93)<sup>b,d</sup></td><td>32.07 (28.69–35.71)<sup>b</sup></td><td>32.70 (29.04–36.72)<sup>d</sup></td><td>0.001</td></tr><tr><td>Living with a partner</td><td>2080</td><td>1622 (77.98)</td><td>200 (75.47)</td><td>249 (69.55)<sup>a,b</sup></td><td>414 (79.01)<sup>b</sup></td><td>759 (81.35)<sup>a</sup></td><td>&lt;0.001</td></tr><tr><td>Epworth score</td><td>2132</td><td>10.00 (6.00–13.00)</td><td>9.00 (5.00–12.00)<sup>e,f</sup></td><td>10.00 (6.00–14.00)<sup>a,e</sup></td><td>10.00 (6.00–14.00)<sup>f</sup></td><td>9.00 (6.00–13.00)<sup>a</sup></td><td>0.001</td></tr><tr><td>Pichot depression score</td><td>2108</td><td>3.00 (1.00–6.00)</td><td>3.00 (1.00–6.00)</td><td>4.00 (1.00–7.00)<sup>a</sup></td><td>3.00 (1.00–6.00)</td><td>3.00 (1.00–6.00)<sup>a</sup></td><td>0.014</td></tr><tr><td>Alcohol intake (glasses·day⁻¹)</td><td>2143</td><td>0.00 (0.00–2.00)</td><td>0.00 (0.00–2.00)</td><td>0.00 (0.00–2.00)</td><td>1.00 (0.00–2.00)</td><td>0.00 (0.00–2.00)</td><td>0.519</td></tr><tr><td>Current or former smoker</td><td>2169</td><td>1259 (58.05)</td><td>160 (58.82)</td><td>230 (61.66)</td><td>336 (60.76)</td><td>533 (54.89)</td><td>0.052</td></tr><tr><td>Medical history</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>COPD</td><td>2205</td><td>410 (18.59)</td><td>39 (13.98)<sup>e</sup></td><td>95 (24.80)<sup>a,b,e</sup></td><td>98 (17.44)<sup>b</sup></td><td>178 (18.14)<sup>a</sup></td><td>0.002</td></tr><tr><td>Diabetes</td><td>2205</td><td>720 (32.65)</td><td>93 (33.33)</td><td>148 (38.64)<sup>a</sup></td><td>207 (36.83)<sup>c</sup></td><td>272 (27.73)<sup>a,c</sup></td><td>&lt;0.001</td></tr><tr><td>Heart failure</td><td>2205</td><td>127 (5.76)</td><td>18 (6.45)</td><td>22 (5.74)</td><td>26 (4.63)</td><td>61 (6.22)</td><td>0.582</td></tr><tr><td>CAD</td><td>2205</td><td>178 (8.07)</td><td>20 (7.17)</td><td>42 (10.97)<sup>a</sup></td><td>51 (9.07)</td><td>65 (6.63)<sup>a</sup></td><td>0.043</td></tr><tr><td>AF</td><td>2205</td><td>214 (9.71)</td><td>30 (10.75)</td><td>26 (6.79)</td><td>49 (8.72)</td><td>109 (11.11)</td><td>0.075</td></tr><tr><td>Stroke</td><td>2205</td><td>149 (6.76)</td><td>28 (10.04)</td><td>22 (5.74)</td><td>34 (6.05)</td><td>65 (6.63)</td><td>0.119</td></tr><tr><td>Polysomnography</td><td>2205</td><td>733 (33.24)</td><td>124 (44.44)<sup>d</sup></td><td>142 (37.08)<sup>a</sup></td><td>209 (37.19)<sup>c</sup></td><td>258 (26.30)<sup>a,c,d</sup></td><td>&lt;0.001</td></tr><tr><td>AHI, events·h⁻¹</td><td>2197</td><td>39.00 (30.00–55.00)</td><td>32.00 (23.00–47.00)<sup>d,e,f</sup></td><td>40.00 (30.00–55.00)<sup>e</sup></td><td>38.00 (30.00–53.00)<sup>c,f</sup></td><td>42.00 (31.00–58.00)<sup>c,d</sup></td><td>&lt;0.001</td></tr><tr><td>AHI REM, events·h⁻¹</td><td>619</td><td>42.08 (24.49–60.34)</td><td>36.21 (23.83–54.17)</td><td>43.11 (21.54–60.00)</td><td>44.65 (27.00–60.54)</td><td>44.61 (26.05–63.44)</td><td>0.061</td></tr><tr><td>ODI, events·h⁻¹</td><td>2113</td><td>34.00 (20.00–52.00)</td><td>24.00 (15.00–39.00)<sup>d,e,f</sup></td><td>34.00 (21.00–52.00)<sup>e</sup></td><td>33.00 (20.00–49.00)<sup>c,f</sup></td><td>37.00 (23.00–55.00)<sup>c,d</sup></td><td>&lt;0.001</td></tr><tr><td>T90, %</td><td>2183</td><td>10.00 (2.80–31.00)</td><td>5.50 (2.00–19.00)<sup>d,e,f</sup></td><td>11.00 (2.00–31.00)<sup>e</sup></td><td>9.00 (2.00–26.00)<sup>f</sup></td><td>13.00 (3.00–36.00)<sup>c,d</sup></td><td>&lt;0.001</td></tr><tr><td>SASHB, %min·h⁻¹</td><td>1550</td><td>63.55 (32.68–123.82)</td><td>43.92 (25.02–78.82)<sup>d,e,f</sup></td><td>71.98 (33.25–133.28)<sup>e</sup></td><td>59.65 (32.20–108.22)<sup>c,f</sup></td><td>75.37 (38.52–145.39)<sup>c,d</sup></td><td>&lt;0.001</td></tr></tbody></table>

Values are expressed as median (interquartile range) or n (%). Labels a, b, c, d, e and f indicate that, within a given line, PAP use subgroups with different letters are significantly different (p<0.05) according to *post hoc* pairwise comparisons after Holm corrections. As an example, for the age variable, there is a significant difference (p<0.001) between PAP use subgroups. *Post hoc* pairwise comparisons indicate that the PAP termination group (label *) is different from PAP use 4–<6 h·day⁻¹ (label b, c) and PAP use ≥6 h·day⁻¹ (label a, c) but not with PAP use 0–<4 h·day⁻¹ (label a, b, c). AF: atrial fibrillation; AHI: apnoea-hypopnoea index; BMI: body mass index; CAD: coronary heart disease; ODI: 3% oxygen desaturation index; OSA: obstructive sleep apnoea; T90: percentage of sleep (or recording) time with oxygen saturation <90%; SASHB: sleep apnoea specific hypoxic burden.

<figure><img src="image_3.png" /><figcaption>FIGURE 1 Flow diagram of the study subjects. OSA: obstructive sleep apnoea; PAP: positive airway pressure.</figcaption></figure>
<table><caption>TABLE 2 Description of the oral antihypertensive drug burden at the start of positive airway pressure (PAP) therapy (T0). Patients were divided into four groups (PAP termination, PAP use 0-<4 h·day⁻¹, PAP use 4-<6 h·day⁻¹, PAP use ≥6 h·day⁻¹) related to PAP use at 1 year</caption><thead><tr><th></th><th>Whole population<br>at start of PAP<br>n=2205</th><th>PAP<br>termination<br>n=279</th><th>PAP use 0-<4<br>h·day⁻¹<br>n=383</th><th>PAP use<br>4-<6 h·day⁻¹<br>n=562</th><th>PAP use<br>≥6 h·day⁻¹<br>n=981</th><th>p-value</th></tr></thead><tbody><tr><td>OAHD score at T0</td><td>2.16±1.11<br>2.00 (1.00-3.00)</td><td>2.04±1.11<br>2.00 (1.00-3.00)</td><td>2.21±1.15<br>2.00 (1.00-3.00)</td><td>2.13±1.13<br>2.00 (1.00-3.00)</td><td>2.18±1.08<br>2.00 (1.00-3.00)</td><td>0.087</td></tr><tr><td>Number of patients with</td><td></td><td></td><td></td><td></td><td></td><td>0.197</td></tr><tr><td>OAHD score =1</td><td>741 (33.61)</td><td>112 (40.14)</td><td>120 (31.33)</td><td>195 (34.70)</td><td>314 (32.01)</td><td></td></tr><tr><td>OAHD score =2</td><td>724 (32.83)</td><td>83 (29.75)</td><td>133 (34.73)</td><td>187 (33.27)</td><td>321 (32.72)</td><td></td></tr><tr><td>OAHD score ≥3</td><td>740 (33.56)</td><td>84 (30.11)</td><td>130 (33.94)</td><td>180 (32.03)</td><td>346 (35.27)</td><td></td></tr><tr><td>OAHD groups at T0</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Renin-angiotensin system blockers</td><td>1700 (77.10)</td><td>196 (70.25)</td><td>293 (76.50)</td><td>452 (80.43)</td><td>759 (77.37)</td><td>0.011</td></tr><tr><td>Diuretics-aldosterone antagonists or<br>diuretics-potassium sparing</td><td>129 (5.85)</td><td>20 (7.17)</td><td>25 (6.53)</td><td>30 (5.34)</td><td>54 (5.50)</td><td>0.642</td></tr><tr><td>Diuretics-loop</td><td>272 (12.34)</td><td>28 (10.04)</td><td>64 (16.71)</td><td>66 (11.74)</td><td>114 (11.62)</td><td>0.032</td></tr><tr><td>Thiazide or thiazide-type diuretics</td><td>881 (39.95)</td><td>105 (37.63)</td><td>154 (40.21)</td><td>208 (37.01)</td><td>414 (42.20)</td><td>0.193</td></tr><tr><td>Calcium channel blockers</td><td>832 (37.73)</td><td>88 (31.54)</td><td>136 (35.51)</td><td>209 (37.19)</td><td>399 (40.67)</td><td>0.029</td></tr><tr><td>Beta blockers</td><td>781 (35.42)</td><td>108 (38.71)</td><td>135 (35.25)</td><td>201 (35.77)</td><td>337 (34.35)</td><td>0.606</td></tr><tr><td>Others</td><td>202 (9.16)</td><td>30 (10.75)</td><td>39 (10.18)</td><td>48 (8.54)</td><td>85 (8.66)</td><td>0.598</td></tr><tr><td>OAHD MPR at T0</td><td>0.95±0.16<br>1.00 (1.00-1.00)</td><td>0.93±0.18<br>1.00 (1.00-1.00)</td><td>0.94±0.17<br>1.00 (1.00-1.00)</td><td>0.94±0.17<br>1.00 (1.00-1.00)</td><td>0.96±0.15<br>1.00 (1.00-1.00)</td><td>0.090</td></tr></tbody></table>

Values are expressed as mean±SD or median (interquartile range), or n (%). MPR: medication possession ratio; OAHD: oral antihypertensive drug; other: alpha-1 blockers or central alpha-2 agonist and other centrally acting drugs or direct renin inhibitors.

<table><caption>TABLE 3 Description of the oral antihypertensive drug (OAHD) burden after 1 year of positive airway pressure (PAP) therapy (T1). Patients were divided into four groups (PAP termination, PAP use 0-<4 h·day⁻¹, PAP use 4-<6 h·day⁻¹, PAP use ≥6 h·day⁻¹) related to PAP use at 1 year</caption><thead><tr><th></th><th>Whole population<br>at 1 year<br>n=2205</th><th>PAP<br>termination<br>n=279</th><th>PAP use<br>0-<4 h·day⁻¹<br>n=383</th><th>PAP use<br>4-<6 h·day⁻¹<br>n=562</th><th>PAP use<br>≥6 h·day⁻¹<br>n=981</th><th>p-value</th></tr></thead><tbody><tr><td>OAHD score at T1</td><td>2.13±1.18<br>2.00 (1.00-3.00)</td><td>2.02±1.21<br>2.00 (1.00-3.00)</td><td>2.15±1.17<br>2.00 (1.00-3.00)</td><td>2.12±1.20<br>2.00 (1.00-3.00)</td><td>2.17±1.17<br>2.00 (1.00-3.00)</td><td>0.141</td></tr><tr><td>Number of patients with</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>OAHD score =0</td><td>83 (3.76)</td><td>11 (3.94)</td><td>20 (5.22)</td><td>19 (3.38)</td><td>33 (3.36)</td><td>0.078</td></tr><tr><td>OAHD score =1</td><td>664 (30.11)</td><td>103 (36.92)</td><td>96 (25.07)</td><td>172 (30.60)</td><td>293 (29.87)</td><td></td></tr><tr><td>OAHD score =2</td><td>710 (32.20)</td><td>80 (28.67)</td><td>137 (35.77)</td><td>187 (33.27)</td><td>306 (31.19)</td><td></td></tr><tr><td>OAHD score ≥3</td><td>748 (33.92)</td><td>85 (30.47)</td><td>130 (33.94)</td><td>184 (32.74)</td><td>349 (35.58)</td><td></td></tr><tr><td>OAHD groups at T1</td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Renin-angiotensin system blockers</td><td>1655 (75.06)</td><td>199 (71.33)</td><td>281 (73.37)</td><td>439 (78.11)</td><td>736 (75.03)</td><td>0.141</td></tr><tr><td>Diuretics-aldosterone antagonists<br>or diuretics-potassium sparing</td><td>133 (6.03)</td><td>21 (7.53)</td><td>20 (5.22)</td><td>30 (5.34)</td><td>62 (6.32)</td><td>0.539</td></tr><tr><td>Diuretics-loop</td><td>284 (12.88)</td><td>33 (11.83)</td><td>62 (16.19)</td><td>80 (14.23)</td><td>109 (11.11)</td><td>0.054</td></tr><tr><td>Thiazide or thiazide-type diuretics</td><td>842 (38.19)</td><td>97 (34.77)</td><td>150 (39.16)</td><td>200 (35.59)</td><td>395 (40.27)</td><td>0.176</td></tr><tr><td>Calcium channel blockers</td><td>817 (37.05)</td><td>84 (30.11)</td><td>134 (34.99)</td><td>210 (37.37)</td><td>389 (39.65)</td><td>0.025</td></tr><tr><td>Beta blockers</td><td>764 (34.65)</td><td>104 (37.28)</td><td>135 (35.25)</td><td>186 (33.10)</td><td>339 (34.56)</td><td>0.679</td></tr><tr><td>Others</td><td>215 (9.75)</td><td>29 (10.39)</td><td>38 (9.92)</td><td>47 (8.36)</td><td>101 (10.30)</td><td>0.636</td></tr><tr><td>OAHD MPR at T1</td><td>0.91±0.19<br>1.00 (0.92-1.00)</td><td>0.88±0.22<br>1.00 (0.84-1.00)</td><td>0.89±0.22<br>1.00 (0.91-1.00)</td><td>0.91±0.19<br>1.00 (0.92-1.00)</td><td>0.93±0.18<br>1.00 (1.00-1.00)</td><td>&lt;0.001</td></tr><tr><td>Consultation number at T1</td><td>9.97±5.68<br>8 (6-13)</td><td>10.95±6.29<br>10 (6-14)</td><td>10.60±6.30<br>9 (6-14)</td><td>9.78±5.37<br>8 (6-12)</td><td>9.56±5.36<br>8 (6-12)</td><td>0.001</td></tr></tbody></table>

Values are expressed as mean±SD or median (interquartile range), or n (%). MPR: medication possession ratio; Other: alpha-1 blockers or central alpha-2-agonist and other centrally acting drugs or direct renin inhibitors.

Primary objective, association of PAP use and OAHD score at 1 year Tables 2 and 3 show the OAHD burden at the start of PAP therapy (T0) and after 1 year of PAP therapy (T1), respectively. The mean±SD OAHD score in the whole population was 2.16±1.11 OAHDs, with no significant difference between PAP subgroups (p=0.087). At T1, there was no significant change in the mean OAHD score in the whole population (OAHD score: 2.13±1.18) and there were no significant differences between PAP subgroups (p=0.141). The mean difference in OAHD score between T0 and T1 was -0.03±0.62, with no significant differences between PAP subgroups (p=0.758). The number of consultations was significantly different between PAP use groups (p=0.001).
<figure><img src="image_4.png" /><figcaption>**FIGURE 2** Sankey diagram for the change in oral antihypertensive drug (OAHD) score during the first year of positive airway pressure (PAP) therapy. Panels are related to PAP use (PAP termination, PAP use 0-<4 h·day⁻¹, PAP use 4-<6 h·day⁻¹, PAP use ≥6 h·day⁻¹).</figcaption></figure>

Figure 2 depicts a Sankey diagram for the change in OAHD score between T0 and T1 in the four PAP use groups. Among patients with PAP adherence ≥ 6 h·day⁻¹, 35.6% remained on three or more OAHDs, 29.9% on one OAHD and 3.4% discontinued OAHDs entirely. For patients with adherence of 4-<6 h·day⁻¹, 32.7% maintained three or more OAHDs, while 3.4% discontinued all OAHDs. In the group with low adherence (0-<4 h·day⁻¹), 33.9% stayed on three or more OAHDs and 5.2% discontinued all OAHDs. Patients who discontinued PAP therapy entirely had similar trends, with 30.5% on three or more OAHDs and 3.9% stopping all OAHDs. Across all groups, most patients maintained stable OAHD scores regardless of their level of adherence and the differences in OAHD transitions between the adherence groups were not statistically significant.

<figure><img src="image_5.png" /><figcaption>**FIGURE 3** Bar plots (%) of the change in oral antihypertensive drug (OAHD) score after 1 year of positive airway pressure (PAP) therapy. Patient groups are related to PAP use (PAP termination, PAP use 0-<4 h·day⁻¹, PAP use 4-<6 h·day⁻¹, PAP use ≥6 h·day⁻¹). White plots represent a stable OAHD score. Cyan plots represent a decrease in OAHD score. Grey plots represent an increase in OAHD score. There are no significant differences between groups in the evolution of OAHD score (p=0.348).</figcaption></figure>
Figure 3 depicts the percentage of patients in the different PAP groups with no change, increase or decrease in OAHD score at T1. There are no significant differences between groups regarding the evolution of the number of OAHDs (p=0.348). For the whole population, 11.93% of patients had a decrease in their OAHD score and 11.07% had an increase. In particular, among patients with PAP adherence of ≥6 h·day⁻¹, 79.1% maintained a stable OAHD score, 9.89% experienced an increase and 11.01% experienced a decrease.

<table><caption>TABLE 4 Multivariable analysis, predictors of changes in oral antihypertensive drug (OAHD) score at 1 year (T1) of positive airway pressure (PAP) therapy</caption><thead><tr><th rowspan="2"></th><th colspan="2">Increase of OAHD score versus stable</th><th colspan="2">Decrease of OAHD score versus stable</th><th rowspan="2">Global p-value</th></tr><tr><th>Adjusted OR (95% CI)</th><th>p-value</th><th>Adjusted OR (95% CI)</th><th>p-value</th></tr></thead><tbody><tr><td>Number of OAHD at T0</td><td>0.96 (0.82-1.12)</td><td>0.595</td><td>2.26 (1.92-2.67)</td><td>&lt;0.001</td><td>&lt;0.001</td></tr><tr><td>Age, 1 year unit at T0</td><td>1.02 (1.01-1.03)</td><td>0.005</td><td>1.01 (0.99-1.02)</td><td>0.328</td><td>0.016</td></tr><tr><td>Diuretics-loop at T0</td><td>0.98 (0.63-1.54)</td><td>0.931</td><td>1.66 (1.12-2.47)</td><td>0.012</td><td>0.037</td></tr><tr><td>Calcium channel blockers at T0</td><td>1.48 (1.08-2.02)</td><td>0.015</td><td>0.890 (0.62-1.28)</td><td>0.523</td><td>0.034</td></tr><tr><td>MPR at T1, for 0.1 unit decrease</td><td>0.92 (0.83-1.03)</td><td>0.168</td><td>1.67 (1.56-1.78)</td><td>&lt;0.001</td><td>&lt;0.001</td></tr><tr><td>Number of consultations at T0</td><td>1.07 (1.05-1.10)</td><td>&lt;0.001</td><td>1.05 (1.03-1.08)</td><td>&lt;0.001</td><td>&lt;0.001</td></tr><tr><td>PAP use at T1</td><td></td><td></td><td></td><td></td><td>0.525</td></tr><tr><td>≥6 h·day⁻¹ versus PAP termination</td><td>0.87 (0.56-1.35)</td><td>0.527</td><td>1.28 (0.79-2.07)</td><td>0.321</td><td></td></tr><tr><td>0-<4 h·day⁻¹ versus PAP termination</td><td>1.18 (0.71-1.93)</td><td>0.525</td><td>1.25 (0.73-2.16)</td><td>0.417</td><td></td></tr><tr><td>4-<6 h·day⁻¹ versus PAP termination</td><td>1.17 (0.74-1.86)</td><td>0.497</td><td>1.25 (0.75-2.09)</td><td>0.394</td><td></td></tr></tbody><tfoot><tr><td colspan="6">MPR: medication possession ratio; T0: start of PAP therapy.</td></tr></tfoot></table>

<figure><img src="image_6.png" /><figcaption>FIGURE 4 Bar plots of the % of patients with their oral antihypertensive drug (OAHD) class assigned at positive airway pressure (PAP) initiation (T0, white plots) and 1 year of PAP therapy (T1 grey plots).</figcaption></figure>

To identify the associations between predictor variables and the change in OAHD score at T1, we performed univariate and multivariate analyses (see respectively supplemental table 2 and table 4). The associations of PAP use with increase or decrease in OAHD score (≥6 h·day⁻¹ versus PAP termination, 0-<4 h·day⁻¹ versus PAP termination, 4-<6 h·day⁻¹ versus PAP termination) were not statistically significant. Multivariate analysis of OAHD score variations
showed that 1) an increase in OAHD score versus a stable score was significantly associated with an increase in age, the use of calcium channel blockers and with each additional consultation, 2) a decrease in OAHD score versus a stable score was significantly associated with an increase in the number of OAHD medications, an increase in the number of consultations, the use of loop diuretics and with a decrease in MPR.

## Secondary objective, association of PAP use and OAHD groups at 1 year

Tables 2 and 3 summarise the distribution of OAHD groups according to 1-year PAP use at T0 and T1, respectively. At T0, statistically significant differences between PAP groups were observed for renin-angiotensin system blockers (p=0.011), loop diuretics (p=0.032) and calcium channel blockers (p=0.029). At T1, statistically significant differences between PAP groups were only observed for calcium channel blockers (p=0.025). When comparing T0 and T1 in the whole population, (see figure 4), there was a statistically significant variation for thiazide (p=0.002) and renin-angiotensin system blockers (p=0.001). 4.58% of the whole population discontinued thiazide at 1 year, whereas 2.81% initiated the treatment at 1 year. Furthermore, 4.90% of the whole population discontinued renin-angiotensin system blockers at 1 year, whereas 2.86% initiated the treatment at 1 year.

Regarding other drug classes, the proportion of patients using loop diuretics increased slightly from 12.34% at T0 to 12.88% at T1. Beta blocker use showed a marginal reduction, with 35.42% at T0 compared to 34.65% at T1. Calcium channel blockers were relatively stable, with 37.73% at T0 versus 37.05% at T1. Finally, the use of aldosterone antagonist or potassium-sparing diuretics, as well as other antihypertensive drugs, remained similar, with minor increases observed for both classes (5.85–6.03% for aldosterone antagonists and 9.16–9.75% for others).

## Secondary objectives, association of PAP use and OAHD groups at 2 years

Similar analyses were performed 2 years after PAP initiation (T2). Supplementary tables 3 and 4 describe the OAHD burden at T0 and T2, respectively. Supplementary figure 1 depicts a Sankey diagram for the change in the OAHD score between T0 and T2 in the four PAP use groups. Supplementary figure 2 depicts the percentage of patients in the different PAP groups with no change, an increase or a decrease in OAHD score at T2. The evolution of the number of OAHDs did not significantly differ between groups (p=0.249). For the whole population, 15.16% of patients decreased their OAHD score and 15.30% of patients increased their OAHD score. Univariate and multivariate analyses are summarised in supplementary tables 5 and 6, respectively. In the multivariable analysis, PAP was not associated with change in the OAHD score at 2 years.

When comparing T0 and T2 in the whole population (see supplementary figure 3), there was a statistically significant variation in thiazide (p=0.002) and renin-angiotensin system blockers (p=0.001). 7.32% of the whole population discontinued thiazide whereas 4.99% initiated the treatment at 1 year and 6.39% of the whole population discontinued renin-angiotensin system blockers whereas 3.82% initiated the treatment at T2. These differences and trends are similar to those observed at T1.
Discussion

To our knowledge, this study is the first to investigate if PAP use is associated with OAHD burden in a large cohort of patients with OSA who had hypertension before initiating PAP. Our results indicate that PAP use is not associated with the evolution of OAHD use at 1 year. Several hypotheses could explain this result.

First, the impact of PAP on BP in our study may not have been sufficient to reduce the number of OAHDs. Our results are aligned with the findings of previous studies that observed reductions in systolic and diastolic BP, of 2 to 3 mmHg, in OSA patients treated with PAP [8, 9]. These reductions, although clinically significant [28], are modest compared to the effects of lifestyle interventions, such as weight loss, a healthy diet and aerobic activities, which have been shown to reduce systolic BP by 5–11 mmHg [4] and reduce the number of OAHDs required for BP control. Thus, the reductions in BP observed with PAP therapy, although coherent with past studies, may not be sufficient to reduce OAHD use [29–31].

These findings supported the current guidelines that prioritise lifestyle measures over PAP for hypertension management [6]. This could also suggest that changes in lifestyle could have a greater impact on BP than PAP alone. Obviously, it is impossible to distinguish between the specific impact of lifestyle changes and PAP as general treatment recommendations include both PAP prescription and lifestyle changes. Randomised trials cannot be used to address this question for ethical reasons and although real-life, observational studies could be used, they would likely be too limited to investigate in depth.

Secondly, there are currently no international recommendations that support deprescribing OAHD. While most patients require lifelong OAHDs, PAP initiation could be an opportunity to reduce medication. In our study, only 11.93% of patients decreased their OAHD score, while 11.07% of patients increased it. One factor that may have limited changes in OAHD use is therapeutic inertia, as it has been reported that research protocols often encourage more proactive treatment changes than routine clinical practice [32–34].

Therefore, our study's real-life design may better reflect typical clinical settings than an RCT, which would limit the possible effects of therapeutic inertia. No published studies, including those limited to patients with OSA and resistant hypertension, have identified a phenotype for patients who could be eligible for OAHD deprescribing. In our study, a decrease in OAHD score at T1 was significantly associated with an increase in the number of OAHD medications at T0, use of loop diuretics, number of consultations and a decrease in MPR. The association between the decrease in OAHD score at 1 year and the initial number of OAHDs could reflect two factors. First, a regression to the mean may explain why patients with a higher initial number of OAHDs are more likely to experience a reduction over time. Second, a higher initial number of treatments may indicate less therapeutic inertia, as patients and their practitioners are more inclined to reassess and adjust medication regimens, possibly influenced by an aversion to a high number of oral treatments.

Thirdly, clinical referral bias may play a significant role in the observed patterns of OAHD prescribing and deprescribing among patients using PAP therapy. Patients who interact more frequently with the healthcare system, including consultations with sleep physicians or primary care providers, are more likely to have their antihypertensive regimen adjusted, whether through the addition or reduction of medications. This interaction could reflect a
clinician's perception of PAP therapy's role in controlling hypertension, potentially leading to deprescribing based on expected BP improvements. Conversely, the same frequent interactions may increase the likelihood of identifying suboptimal BP control, prompting the prescription of additional OAHDs. Our findings corroborate this dual dynamic: in the multivariable logistic regression models, an increase in the number of consultations was significantly associated with both a higher likelihood of reducing the number of OAHDs and a higher likelihood of increasing them. This suggests that the effect of frequent healthcare interactions is complex, potentially reflecting clinician-driven therapeutic adjustments in response to individual patient trajectories. Furthermore, other factors such as regression to the mean of BP measurements, patient-initiated lifestyle improvements or the "healthy user effect" (where more adherent patients engage in a broader spectrum of health-promoting behaviours) may confound these observations [35, 36]. These intricacies underline the need for cautious interpretation of OAHD prescribing patterns in observational studies and emphasise the importance of accounting for referral bias and unmeasured confounders in future analyses.

Only one study based on health administrative data has examined the association of OSA therapy (PAP or mandibular advancement) initiation on OAHD groups. REVOL et al. [37] reported a significant decrease in the median cumulative cost of antihypertensive therapy after starting OSA therapy. At the same time, the authors found a significant decrease in the use of calcium channels blockers and RAS blockers (p=0.0133). Neither of these trends occurred in the control group without OSA [37]. In our study, we found no significant decrease in channel blockers but observed a similar reduction in RAS blockers. Unlike REVOL et al. [37], we were able to assess the relationship between groups of OAHD and PAP use, and we report that PAP use was not associated with changes in OAHD groups 1 year after PAP initiation.

## Strengths and limitations of the study

The IRSR Pays de la Loire multicentre sleep cohort study is a well-described externally validated cohort [15]. The linkage between the clinical data of Pays de la Loire Sleep Cohort and the SNDS database is a major strength, allowing robust comparisons of clinical data with OAHD delivery and adherence data. The absence of an association between PAP use and changes in OAHD score at 1 year was confirmed at 2 years, suggesting no time effect on our results. Unfortunately, we did not have access to specific data on the date of initial arterial hypertension diagnosis, which could influence the observed outcomes. To mitigate this effect, we only included patients whose hypertension treatment had been stable for at least 3 months prior to initiating PAP therapy. The cohort was identified as hypertensive. We acknowledge that some medications may have been prescribed for other cardiovascular indications. Such potential misclassifications could introduce biases into the analysis.

Our cohort represents a European population with universal healthcare coverage, ensuring that financial barriers did not limit access to care or medications. This reduces biases linked to socioeconomic disparities. However, the findings may be less generalisable to populations in healthcare systems where access to treatment is influenced by cost considerations.
Furthermore, the cohort of hypertensive patients analysed in our study is representative of the hypertensive population in developed countries, characterised in particular by advanced age, excess weight and the presence of multiple comorbidities [6].

The main limitation of our study is the lack of evaluation of potential confounders, such as weight, diet and physical activity. A healthy user effect, where adherent patients engage in other beneficial health behaviours, cannot be ruled out as a confounder [35, 36]. Furthermore, as this study was observational, our findings are subject to residual confounding and we cannot establish causality [38]. Undetected health changes, such as improvements in lifestyle or comorbidities not captured in our dataset, may also influence the observed outcomes. Data on cholesterol levels and other cardiovascular risk factors were not available. Their absence limits the ability to comprehensively stratify cardiovascular risk and therefore could impact decisions to change medications. Another key limitation is the absence of data on the dosage of antihypertensive drugs, which can significantly affect blood pressure control. We measured OAHD delivery, which is not strictly OAHD adherence [36]. Additionally, we lacked measurements of clinic and home BP at baseline and follow-up, further complicating the interpretation of changes in antihypertensive therapy. Factors such as side-effects or non-BP-related indications may drive OAD changes, adding complexity to the interpretation of our findings.

Furthermore, the study was not designed to specifically investigate resistant hypertensive patients and there was no measure of BP patterns during the night. Finally, part of our results can be explained by an unidentified bias inherent in the real-life design of our study.

## Conclusion

PAP use was not associated with the overall change in OAHD score after 1 year of PAP therapy. Nevertheless, factors such as age, initial OAHD score, specific OAHD classes, frequency of consultations and MPR were significantly associated with changes in OAHD scores. Further research is warranted to clarify the impact of PAP use on OAHD burden, both in the general hypertensive population and in patients with resistant or refractory hypertension, patients with non-dipper or riser patterns. These studies should not only evaluate the impact of PAP use on the number of OAHDs, but also the dose of OAHDs.

This approach would require reliable methods including repeated BP evaluations and biological parameters, such as renal function and urinary flux.

## Acknowledgements:

We thank the Pays de la Loire Research Institute, promoter of the Institut de Recherche en Santé Respiratoire (IRSR) Pays de la Loire Sleep Cohort, and the National Health Insurance Fund for giving us access to the French administrative health care database.
**Data availability:**

The datasets used and/or analysed during the current study are available from the
corresponding author on reasonable request.

**Provenance:**

Submitted article, peer reviewed.

**Author contributors:**

D. Jaffuel, E. Nogue, F. Roubille, J-P. Mallet, S. Bailly, N. Molinari and F. Gagnadoux weresubstantially involved in the study design; F. Goupil, A. Thomas, C. Hervé, P. Masson, A. Bizieux-Thaminy, M. Blanchard, S. Kerbrat, W. Trzepizur and F. Gagnadoux were substantially involved in data acquisition; D. Jaffuel, E. Nogue, F. Roubille, J-P. Mallet, S. Bailly, S. Kerbrat, N. Molinari and F. Gagnadoux were substantially involved in data analysis or interpretation of data; D. Jaffuel, E. Nogue, F. Roubille, J-P. Mallet, S. Bailly, S. Kerbrat, A. Sabil, W. Trzepizur, C. Roubille, A. Bourdin, N. Molinari and F. Gagnadoux were substantially involved in the critical revision of the paper for important intellectual content; D. Jaffuel, E. Nogue, F. Roubille, A. Salin, S. Kerbrat, N. Molinari and F. Gagnadoux were substantially involved in drafting the article. All authors approved the version submitted for publication.

**Conflict of interest:**

D. Jaffuel reports personal fees and nonfinancial support from Sefam and Nomics; personal fees from Lowenstein, Jazz and Biprojet; and grants and personal fees from Novartis, all outside the submitted work. E. Nogue, M. Blanchard, S. Kerbrat, C. Roubille, S. Skinner, S. Bailly, F. Goupil, A. Thomas, C. Hervé, P. Masson and A. Bizieux-Thaminy have nothing to disclose. F. Roubille reports personal fees from AstraZeneca, Servier, Boehringer Ingelheim, Vifor, Bayer, Pfizer, Novo Nordisk, Air Liquid, Abbott and Lilly; and grants and personal fees from Novartis, all outside the submitted work. J-P. Mallet reports personal fees from Novartis, GSK, Chiesi and PulmonX outside the submitted work. A. Sabil is an employee of Sefam Medical. W. Trzepizur reports payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing or educational events from AstraZeneca and Bioprojet; and support for attending meetings from Asten Santé, all in the past 36 months. A. Bourdin reports grants and personal fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Sanofi Regeneron and Chiesi; and personal fees from Amgen and Novartis, all outside the submitted work. N. Molinari reports personal fees from ONIRIS outside the submitted work. F. Gagnadoux reports support for the present work from ALTADIR (Institut Recherche en Santé Respiratoire des Pays de Loire); and consulting fees from Resmed, Inspire Medical, Sefam, Bioprojet and Asten Santé; payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing or educational events from Resmed, Inspire Medical, Sefam, Bioprojet and Cidelec; and support for attending meetings and/or travel from Resmed, Inspire Medical, Sefam and Bioproject, all in the past 36 months.

**Support statement:**

This study was supported by the IRSR des Pays de Loire.
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