Herein, we evaluated serum Vit D levels in OS patients over a period of 12 months of CPAP treatment. Our results indicated an improvement in Vit D levels following CPAP therapy. Additionally, patients adherent to CPAP therapy had higher serum Vit D levels compared to those non-adherent to treatment.

Although a connection between Vit D insufficiency and COPD has been previously documented, the causal nature of this relationship and the potential effects of Vit D supplementation still need to be established [19]. Results from a meta-analysis of 21 studies revealed decreased Vit D levels in COPD patients compared with controls, especially in those with severe COPD and those experiencing exacerbations [20]. In the same meta-analysis, patients with lower Vit D levels were more likely to have COPD and severe COPD, while COPD exacerbations were independent of Vit D status [20]. Furthermore, Vit D supplementation in COPD patients improved lung function, 6-minute walk distance and reduced acute exacerbations, as well as sputum volume and CAT score [9].

Though conflicting, overall evidence suggests that serum Vit D levels are reduced in OSA patients [21, 22]. In a large prospective cohort study, patients with Vit D insufficiency had an increased propensity of developing OSA. This was more evident for obese patients with large waist circumference [23]. Several studies have also identified an association between Vit D status and OSA severity [21, 22, 24]. To further strengthen this hypothesis, in a recent meta-analysis patients with moderate and severe OSA had significantly decreased 25(OH)D levels and presented with Vit D insufficiency more frequently in comparison with non-apneic individuals, regardless of age, BMI and place of residence [25].

Few studies have explored the link between Vit D insufficiency and OS. The 2005–2008 National Health and Nutrition Examination Survey reported a high prevalence of Vit D insufficiency and deficiency among OS patients [26]. We have previously compared 25(OH)D serum levels between 30 OS patients, 30 OSA patients and 30 healthy controls [11]. Patients with OS had diminished serum 25(OH)D levels compared with OSA patients and controls (14.5 versus 18.6 versus 21.6 ng/mL, p < 0.001). In the OS group, AHI and FEV1 were identified as the principal determinants of serum 25(OH)D levels [11]. At present, there is a paucity of studies examining the effect of CPAP therapy on Vit D status in OS patients.

In the present study, CPAP therapy resulted in an increase of serum Vit D levels in OS patients at 12 months compared to baseline levels. Yet, the effect of CPAP treatment on Vit D levels in patients with OSA remains undefined [27]. Data from a recent meta-analysis failed to corroborate the positive impact of CPAP therapy on Vit D status in OSA patients, and this was regardless of treatment duration [25]. However, the findings of this study should be interpreted cautiously, given the limited number of studies analyzed in the meta-analysis and the inclusion of OSA patients with poor adherence to CPAP therapy. In the study of Liquori et al. [28], 12 months of CPAP therapy resulted in increased serum Vit D levels, with a notably stronger effect among obese patients and those with good adherence to therapy. Transitioning from inadequate to adequate Vit D levels was more common in OSA patients with good CPAP compliance compared to those not adequately using CPAP treatment. Their results were replicated in our study, where adequate treatment adherence was a significant factor for achieving adequate Vit D levels in OS patients and led more frequently to the normalization of Vit D status. Similarly, in the study of Siachpazidou et al., adequate Vit D status was correlated with higher CPAP use both after 3 and 12 months of therapy, with daily CPAP usage emerging as a significant predictor of 25(OH)D levels after 1 year of treatment [29]. In a recent study involving 60 patients, 12 months of CPAP treatment improved bone mineral density and Vit D serum levels in males with severe OSA [30].

In COPD patients, Vit D deficiency may be due to reduced sun exposure as a result of limited outdoor activity, reduced cutaneous synthesis caused by aging and smoking, increased Vit D catabolism resulting from glucocorticoid treatment and lower Vit D storage capacity [31]. Excessive daytime sleepiness, a key feature in OSA, is thought to reduce outdoor activities of OSA patients, limiting sun exposure and reducing cutaneous synthesis of Vit D [32]. Short sleep duration secondary to sleep fragmentation, another main feature of OSA, increases the risk for Vit D insufficiency, and in OSA patients Vit D serum levels have been inversely associated with sleep stage transitions, an indicator of sleep fragmentation [21, 33]. In addition, nocturnal intermittent hypoxia accompanying apneic events negatively affects Vit D status through a mechanism that involves hypoxia-inducible factor (HIF)-1α [34]. Based on the above assumptions, smoking, frequent COPD exacerbations that require glucocorticoid treatment, excessive daytime sleepiness and severe OSA, associated with sleep fragmentation and nocturnal hypoxia could be considered as the main predictors of low Vit D levels in OS patients.

The underlying pathophysiological mechanisms responsible for the positive effects of CPAP treatment on Vit D levels are multifactorial. Data show that OSA patients with short sleep duration are exposed to an increased risk of Vit D deficiency [35]. This is because excessive daytime sleepiness, a common feature of OSA, may limit outdoor activity and reduce Vit D synthesis. Of note, several lines of evidence report that CPAP improves long-term sleep duration, sleep quality and architecture in those patients [36]. Therefore, CPAP therapy by normalizing sleep architecture and stabilizing sleep stage transition, significantly improves daytime sleepiness, decreases fatigue and increases energy in patients with OSA, thus increasing outdoor activity, sun exposure and Vit D skin production [37, 38]. Finally, nocturnal intermittent hypoxia, which is related to apneic events, has been previously associated with low Vit D levels [21]. This is also true for treatment with CPAP, which alleviates nocturnal hypoxia and attenuates its effect on Vit D levels [39].

Nonetheless, our study has limitations. First, the number of patients included in the study was relatively small, but this was due to the small prevalence of OS in the general population. Second, females are significantly under-represented in our study population. This aligns with the low prevalence of both COPD and OS among females. Nevertheless, this gender imbalance could have an impact on the generalizability of the study findings. Lastly, the potential effect of sun exposure and/ or dietary habits among participants was not evaluated. However, all participants reside in the same region of Greece (having similar exposure to sun) and share similar dietary and clothing characteristics.

In conclusion, this study reports that 12 months of CPAP treatment resulted in improved Vit D serum levels in OS patients. This might be due to the improvement of OSA and its related symptoms. The present study highlights the importance of good compliance with CPAP therapy for OS patients, in order to limit sequelae inherent to both OSA and COPD. Further studies with larger sample sizes in this field are still needed.