Introduction

Obstructive sleep apnoea (OSA) is a sleep-related breathing disorder characterized by frequent breathing cessation and/or reduction in airflow due to partial or complete obstruction of the upper respiratory airways [1]. Worldwide, OSA has been reported to affect nearly 1 billion adults aged 30–69 years [2], making it a common condition. For individuals with OSA who experience symptoms, these include excessive daytime sleepiness (EDS), mood alterations, and impairment of cognition [1, 3, 4]. In addition, the rate of several significant cardiovascular, cerebrovascular and metabolic comorbidities is increased in the presence of OSA, and OSA is also associated with higher all-cause mortality [5,6,7,8,9].

In addition to clinical anamnesis, polysomnography (PSG) and cardiorespiratory polygraphy (PG) are recommended for establishing a diagnosis of OSA and determining the most appropriate treatment option [1, 10, 11]. The gold standard treatment for individuals with moderate to severe OSA is positive airway pressure (PAP), which is highly effective in suppressing respiratory disturbances during sleep and improving symptoms [12, 13].

A retrospective cohort study based on German health claims data highlighted the value of positive airway pressure (PAP) therapy for the treatment of OSA [14]. The results showed that the mortality rate at 4 years after PAP prescription in individuals with OSA was significantly lower than that in subjects with OSA who were not treated with PAP (4.8% vs. 6.5%, respectively; p = 0.0175). In addition, the average length of stay per hospitalisation at 4‑year follow-up was significantly shorter in individuals with OSA who were treated with PAP therapy versus those who were not (7.9 vs. 9.3 days; p < 0.05) [14].

In Germany, the Federal Joint Committee (G-BA) issued a legally binding prerequisite for the initiation of PAP treatment within the framework of statutory health insurance (SHI) [15]. First, medical history should be taken and clinical examinations performed to exclude other forms of sleep-disordered breathing (SDB) and any other treatable underlying diseases (stages 1–2). Next, PG should be performed (stage 3). PSG is only indicated if the results of PG do not allow clear determination of the diagnosis, or to facilitate treatment (stage 4). If an indication for PAP is confirmed, initial therapy set-up should generally occur during two consecutive nights of PSG. PG should be repeated 6 months after CPAP initiation to monitor the effects of PAP therapy. Additional routine PG is not required, but follow-up examinations can be performed if problems with therapy arise.

Despite the therapeutic value of PAP and clearly defined procedures for its use in Germany, there are no current data on the number of patients with OSA being treated with PAP therapy. Therefore, the objective of this study was to collect data on the prevalence of PAP prescription among individuals with OSA in Germany, and to determine the predictors of PAP prescription in these individuals.

Methods

Study design and data source

This retrospective observational study used an anonymized German claims research database that included an approximately 5% sample of the German population who were covered by SHI. The dataset included more than 4 million insured persons from German SHI providers. Data were age- and sex-adjusted to the German population and are considered to be representative of this population in terms of morbidity, mortality and prescription drug use [16]. The dataset has been used previously to assess a large sample of the German SHI population for representative prevalence estimates of narcolepsy and chronic myeloid leukaemia [17, 18].

In accordance with the German Society for Epidemiology recommendations [19] and the STROBE (STrengthening the Reporting of OBservational studies in Epidemiology) guidelines [20], a detailed predefined analysis protocol was developed. The results of these analyses were reported according to the German Reporting Standard for Secondary Data Analyses [21].

Study methodology was similar to that in a previous analysis [22]. All data for healthcare services were retrieved from the German SHI billing records submitted by physicians, pharmacies and other healthcare providers, and are predominantly free of selection biases. Claims data are transferred directly from healthcare providers to a specialized data centre owned by the health insurance companies, which provides information technology and data warehousing. Claims data undergo regular audit (by insurers for reimbursement purposes) and are managed in accordance with German Social Law (paragraphs 287 SGB V and 75 SGB X). Prior to entry into the database, data were anonymized with respect to the following: identity of the insured individual; identity of the healthcare provider(s) and the specific insurance. Data included in this analysis cover the years 2015 to 2020.

Study participants

Individuals included in the analysis were aged ≥ 18 years at the index date. The PAP-treated group included previously untreated (i.e. treatment-naïve) individuals with a diagnosis of OSA who had had a PSG claim within 1.5 years after a claim for PG, and then a claim for CPAP within 1 year after PSG; the index date was defined as the date of first PAP prescription (Fig. 1).

Fig. 1
figure 1

Inclusion of positive airway pressure (PAP)-treated individuals with obstructive sleep apnoea (OSA); max. maximum, min. minimum, PG polygraphy, PSG polysomnography

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To allow determination of predictors of PAP prescription, a control group was created that included individuals with newly diagnosed treatment-naïve OSA who were not prescribed PAP therapy or any other specific treatment for OSA (Fig. 2). This included two groups of patients: 1) individuals who underwent the same diagnostic process as the PAP-treated group, but did not receive PAP therapy (those with a claim for PSG between 1 January 2015 and 30 June 2018 and a claim for PG within the 1.5 years before PSG, plus at least one outpatient or inpatient diagnosis of OSA in the same quarter that PSG was performed and no claim for PAP therapy or other OSA-specific treatment); and 2) individuals who stopped the OSA diagnostic process after initial PG then had a subsequent OSA claim (coding for PG between 1 January 2016 and 30 June 2018 and at least one outpatient or inpatient OSA claim in the same quarter as the PG, plus no claims relating to OSA diagnoses or PAP prescription in the four quarters prior to inclusion, no PSG coding within 1.5 years after PG and no coding for PAP therapy between 1 Jan 2015 and 31 Dec 2020). Study participants were followed up for a minimum of 2.5 years, until January 2020.

Fig. 2
figure 2

Inclusion of untreated individuals with obstructive sleep apnoea (OSA) into the control group; PAP positive airway pressure, max. maximum, min. minimum, PG polygraphy, PSG polysomnography

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Statistical analysis

Differences between individuals with OSA in the PAP-treated and control (untreated) groups were assessed using multivariate logistic regression (logit model). Categorical outcome variables were analysed descriptively using frequencies and percentages, and exact chi-squared values were used for between-group comparisons. Continuous variables are described using mean and standard deviation values, and two-sided t-tests were used for between-group comparisons. A two-sided p-value of < 0.05 was defined as indicating statistical significance. All statistical analyses were performed using MS Excel 2016 (Microsoft, Redmond, WA, USA) and SAS 9.4 (SAS Institute, Cary, NC, USA).

Results

Study population

Of 4.83 million individuals in the age- and sex-stratified dataset, 78,823 had at least one diagnosis of OSA. Study inclusion criteria were met by 12,297 individuals treated with PAP, while 10,020 who did not receive PAP were included in the control group (Fig. 3). Average follow-up time per person was 3.5 years.

Fig. 3
figure 3

Participant inclusion flowchart; PAP positive airway pressure, OSA obstructive sleep apnoea, PG polygraphy, PSG polysomnography

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Overall, the study population had a mean age of 58.2 ± 18.8 years and 67% were male (Table 1). Compared with the control group, individuals in the PAP-treated group were significantly more likely to be male, significantly older, had significantly higher rates of coronary artery disease without myocardial infarction, obesity, diabetes, hypertension and depression, and were significantly more likely to be receiving treatment with beta-blockers, lipid-modifying agents, angiotensin-converting enzyme inhibitors, and nonsteroidal anti-inflammatories and antirheumatics, although between-group differences in rates of depression and use of most medical therapies were numerically small (Table 1).

Table 1 Patient demographic and clinical characteristics at baseline, overall and in groups with versus without continuous positive airway pressure treatment
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Diagnostic pathway

The average time between PG and PSG was 109 ± 98 days (median 81 days; interquartile range [IQR] 40–146), and there was a mean of 34 ± 64 days (median 9 days; IQR 2–33) between the initial PSG and the first PAP prescription. Thus, the average time between first PG and first PAP prescription was 173 ± 111 days (median 90 days; IQR 45–168). Overall, 82% of patients underwent PSG within 6 months after PG. Three quarters of patients had another PG and one in two patients had another PSG within 3 years after the index date.

Rate and predictors of PAP prescription

Just over half of the 22,317 individuals with OSA included in the current analysis (55%) were treated with PAP. Significant predictors of PAP prescription in multivariate logistic regression analysis were overweight/obesity, hypertension, heart failure, other cardiovascular diseases, gastro-oesophageal reflux disease, breathing abnormalities (ICD-10-GM code R06), vasomotor and allergic rhinitis, and somatoform disorders (Table 2). Use of a variety of medications, especially angiotensin receptor blockers, inhaled adrenergics or other inhaled drugs, was also a significant predictor of PAP prescription (Table 2).

Table 2 Predictors of continuous positive airway pressure treatment on multivariate logistic regression analysis
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Discussion

This analysis of German SHI data found that just over half of all eligible individuals with OSA were prescribed PAP. In the absence of data on variables used to phenotype individuals with OSA in clinical practice, predictors of PAP prescription in this insured population included the presence of a variety of comorbidities (especially metabolic and cardiovascular diseases) and use of several classes of medication. However, clinical variables might play a more important role in determining PAP prescription.

One potential explanation for the low rate of PAP prescription in the study population could be that a substantial proportion of individuals with mild sleep apnoea on cardiorespiratory polygraphy may not have been referred to a sleep laboratory for further investigation, and were instead managed using options other than PAP, such as weight reduction and avoiding the supine position during sleep. Overall, the current findings provide valuable real-world data that are representative of the individuals and activities in clinical practice, and can therefore help to inform the overall care of individuals with OSA.

There is currently a lack of data on rates of PAP prescription in patients with OSA, and about factors that predict the prescription of PAP therapy. A recent meta-analysis found significant associations between six factors and the purchase of a PAP device by patients with OSA [23]. These were older age, more years of education, higher income, current smoking, higher Epworth Sleepiness Scale score and higher apnoea–hypopnoea/respiratory disturbance index. Interestingly, the association between the presence of hypertension/cardiovascular disease and PAP device purchase did not reach statistical significance in that analysis [23]. In contrast, cardiovascular diseases, including hypertension and heart failure, were significant predictors of PAP initiation in treatment-naïve patients with OSA in the current study.

Overall, the number of comorbidities in our study population was high, especially coronary artery disease, obesity, chronic obstructive pulmonary disease, diabetes mellitus and arterial hypertension, which is consistent with database studies from other countries [24, 25]. Obesity is a well-known risk factor for the development of OSA [26], and overweight/obese patients were more likely to start PAP therapy in the current analysis.

The burden of mental health-related comorbidities in the study population was relatively high, with nearly a quarter of all participants (22.8%) having depression, similar to rates reported in other studies of individuals with OSA [27, 28]. Relatively high rates of mental health issues in patients with OSA may be due to a variety of factors. OSA symptoms such as EDS, fatigue, poor concentration, irritability, psychomotor issues and weight gain can overlap with symptoms of depression [29]. Alternatively, depression might also be caused by residual EDS, or depression could coexist with OSA symptoms (such as EDS) [30]. Data from a small study (n = 50) indicated a possible connection between depression and residual EDS in OSA, and suggested that PAP therapy might be able to improve both [31].

The German SHI claims data used for this analysis provide a comprehensive, patient-level picture of all reimbursed health-related services, allowing determination of epidemiological estimates and healthcare resource utilization. The large dataset is representative of the German population [16] and, with approximately 90% of the population enrolled in the SHI system and no opt-out possibility for this anonymized analysis, Germany offers a near-ideal setting to analyse population-based epidemiological estimates. Another strength of the current analysis are the objective and consistent definitions of PAP usage or non-usage (control group).

There are also several limitations that need to be considered when interpreting the findings of this study. Firstly, the maximum observational period of 6 years may not reflect the entire diagnostic process and some patients with later treatment of OSA might have been missed due to the specific timeframes applied. Secondly, the strict inclusion criteria applied to simulate the diagnostic scheme could have biased the study results. It is likely that these criteria have high specificity but poor sensitivity for identifying treatment-naïve OSA patients in the population. Thirdly, specific PSG and PG results were not available in the claims database used, and it was not possible to distinguish between diagnostic and titration PSGs. This means that there are no data on the severity of OSA, and therefore the specific indication for PAP therapy (which is primarily recommended for individuals with moderate to severe OSA). In addition, the control group did not receive treatment for OSA, not even alternatives to PAP such as mandibular repositioning devices. One potential limitation of the large population included in this study is that small between-group differences that achieved statistical significance may not be clinically significant, so this needs to be considered when interpreting the study data.

Conclusion

In this analysis of German SHI data, just over half of all eligible patients with OSA were prescribed PAP. This suggests that a significant proportion of individuals with OSA went untreated despite clear evidence of the benefits of and recommendations for treating OSA with PAP [12, 31]. The presence of a variety of comorbidities predicted the prescription of PAP therapy in the study population. Future research should focus on identifying ways to increase utilization of PAP in eligible individuals with OSA to optimize clinical outcomes.