With the rising global epidemic of obesity caused by a diet-related obesogenic lifestyle, the prevalence of obesity-associated sleep disorders has increased. Patients with hypoventilation in obesity and concomitant severe obstructive sleep apnea (OSA) are at a high risk of developing more prominent nighttime and daytime sleep disorder-induced signs and symptoms. This could increase the risk for early pulmonary hypertension development, consequently leading to significant cardiovascular morbidity and mortality secondary to right heart dysfunction or failure and fatal cardiac arrhythmia due to secondary hypoxemia in case of missed diagnosis [1-3]. Hypoventilation in obesity comprises four stages. The first two stages are associated with intermittent nocturnal hypercapnia. A complete washout of nocturnal accumulated carbon dioxide (CO₂) is observed in Stage 1, while Stage 2 involves an incomplete washout of the retained CO₂. Stage 3, termed obesity hypoventilation, is associated with persistent daytime hypercapnia with a partial pressure of CO₂≥45 mm Hg along with nocturnal CO₂ retention. Stage 4, termed obesity hypoventilation syndrome, presents hypoventilation with cardiometabolic abnormalities. Our patient only fulfilled the criteria for Stage 1 of obesity-induced sleep hypoventilation, with a high body mass index (BMI, 43 kg/m²) and an increase in nocturnal total carbon dioxide content (TCO₂) by ≥10 mm Hg compared to the awake supine TCO₂ value for over 10 minutes, without evidence of sustained daytime hypoventilation. In such patients, continuous positive airway pressure (CPAP) therapy together with weight loss should be considered the initial treatment choice to reduce the risk of cardiovascular morbidity and mortality. The patient finally lost 6 kg of body weight solely through healthy lifestyle modifications, with strict dietary restrictions and regular physical exercise. A marked improvement was noted in the clinical symptoms, and the apnea-hypopnea index (AHI) reduced to 10 events/h. Therefore, we aimed to highlight the occurrence of occult hypercapnia in severe nocturnal hypoxemia during sleep and to choose the appropriate positive airway pressure (PAP) therapy in morbidly obese patients with both these disorders.

A 46-year-old man with underlying hypertension presented with a chief complaint of non-refreshing sleep with excessive daytime sleepiness, morning headaches, and memory lapses for the past 1–2 years. He also experienced troublesome symptoms, such as loud snoring, apneic episodes with gagging and choking sensations during nocturnal sleep, and a sense of breathlessness on climbing more than two floors. Physical examination revealed the following: body weight, 102 kg; height, 154 cm; BMI, 43 kg/m²; neck circumference, 46 cm; macroglossia; excessive throat tissue density and lateral peritonsillar narrowing; Mallampati score, 3; and Grade 3 tonsillar hypertrophy. The Epworth sleepiness scale (ESS) score was 15. Clinical examination revealed Class III obesity (severely obese), and profuse upper airway soft tissue density was the underlying cause of the aforementioned symptoms. Therefore, we performed nighttime polysomnography (PSG), including TCO₂ monitoring, as we suspected the co-existence of sleep-related breathing disorder and obesity-associated sleep hypoventilation (OASH). The PSG report revealed that the total sleep time was 6 hours and 47 minutes. The AHI was 157 events/h, obstructive apnea index was 127.2 events/h, mixed apnea index was 23 events/h, central apnea index was 0.9 events/h, obstructive hypopnea index was 5.9 events/h, and snore index was 216.7 events/h (Figure 1). The oxygen desaturation index was 148.6 events/h, with a mean saturation pressure of oxygen (SpO₂) of 73% and minimal SpO₂ of 34%. The total arousal index was 72.4 events/h, and the respiratory arousal index was 52.5 events/h. The mean awake TCO₂ was 32.6 mm Hg, indicating no daytime hypoventilation. Nocturnal TCO₂ monitoring showed a TCO₂>50 mm Hg for 41.1 minutes, with the highest one recorded as 58.4 mm Hg. The highest heart rate (HR) was 120 bpm, and the average HR during sleep was 96 bpm. Therefore, a diagnosis of OASH with hypoxemia and concomitant severe OSA was made. A split-night PSG study for CPAP titration revealed that the appropriate CPAP level for this patient was 10 cm H2O, wherein the AHI reduced to 10 events/h. The patient was treated with regular CPAP therapy during nighttime sleep and adopted healthy lifestyle modifications with regular physical exercise for weight reduction. Although the patient lost 6 kg over 6 months, the BMI remained at 40 kg/m². A follow-up PSG performed 3 months after CPAP use showed an AHI of 10 events/h, and the ESS score reduced to 9. The pulmonary function test results showed a mild degree of restrictive airway dysfunction with a forced vital capacity (FVC) of 2.73 L (65%), forced expiratory volume in 1 second (FEV1) of 3.0 L (72%), and no evidence of fixed obstructive airflow limitation (FEV1/FVC, 0.71). No evidence of air-trapping (residual volume/total lung capacity, 39%) and no limitation in diffusion capacity (diffusing capacity of the lung for carbon monoxide per alveolar volume, 88%) were observed. The distance covered in the 6-minute walk test was 480 m. The patient’s walking capacity almost reached the lower normal limit, although there was no exertion-induced O₂ desaturation (>88%), indicating no significant exertional intolerance or exertion-induced hypoxemia, which indirectly revealed no significant right ventricular dysfunction.

The patient was morbidly obese with nocturnal hypercapnia and hypoxemia due to nocturnal hypoventilation alone without any evidence of daytime hypercapnia; therefore, the condition was classified as Stage 1 of hypoventilation in obesity, i.e., OASH, indicating that intermittent nocturnal hypercapnia fully recovered in the daytime. However, we did not check the daytime serum bicarbonate (HCO₃) level or perform arterial blood gas analysis, as it was an outpatient case. Concurrently, the patient had severe OSA with an AHI of 157 events/h. Since the AHI was >30 events/h and no daytime hypoventilation-induced daytime hypercapnia was observed, our treatment plan initially aimed at splinting the upper airway, where frequent complete or partial collapse occurred during sleep due to excessive local fat mass in the throat and oropharyngeal tissue. Thus, we titrated and treated the patient with CPAP therapy at a driving pressure of 10 cm H2O. The patient exhibited a marked positive response to CPAP therapy, as the AHI reduced to 10 events/h, and both nighttime airway obstruction signs and secondary daytime symptoms improved significantly. Although effective weight reduction is crucial for successful OASH and OSA treatment, the patient could not achieve it adequately because more efforts were needed to decrease the BMI to <30 kg/m². Further effective reduction in the patient’s body weight should be continuously assessed for a better outcome in the coming months to years.

Obese patients with BMI ≥30 kg/m² may have concomitant OASH and OSA, even though they may not exhibit significant hypoventilation-induced daytime hypercapnia (partial pressure of CO₂ [PaCO₂] >45 mm Hg). The pathophysiologic mechanism of nocturnal hypercapnia in such patients is attributed to decreased pharyngeal luminal size and increased upper airway collapsibility during sleep due to excessive fat deposition around the upper airway, chest, and abdominal walls. This can make patients vulnerable to concomitant ventilatory mechanical constraints, affecting the chest wall and diaphragmatic mechanics and causing nocturnal rostral fluid shift from the legs to neck. Additionally, reduced central respiratory drive is observed due to impaired leptin level and sensitivity, attributed to excessive adipose tissue stimulating the neural ventilatory center and causing prolonged sleep apnea–hypopnea, inter-apneic hypoventilation, and diurnal hypoventilation [1-4]. Therefore, we should consider the occurrence of OASH, i.e., Stages 1 and 2 of hypoventilation in obesity, in morbidly obese patients, even though they do not fulfill the criteria for obesity hypoventilation syndrome (OASH with sustained daytime hypercapnia [PaCO₂≥45 mm Hg] and cardiometabolic abnormalities such as stroke, congestive heart failure, or cardiac dysrhythmia) [1-4]. In these patients, measuring daytime serum HCO₃ levels to detect whether it is <27 mmol/L (complete washout of nocturnally accumulated CO₂) or >27 mmol/L (incomplete washout) is another alternative when arterial blood gas analysis or continuous arterial CO₂ monitoring is not easily available [5]. The decision to choose the appropriate initial therapy for these patients depends on AHI severity and persistent daytime hypercapnia, with or without pulmonary hypertension [4-6]. If the AHI severity is >30 events/h, without sustained daytime hypercapnia (PaCO₂ >45 mm Hg) and/or serum HCO₃ <27 mmol/L, CPAP should be the initial PAP therapy option [4,6,7]. If the AHI is <30 events/h, with sustained daytime hypercapnia (PaCO₂ >45 mm Hg) and/or serum HCO₃ ≥27 mmol/L and pulmonary hypertension or right heart dysfunctional evidence, then BiPAP therapy should be considered [4-7]. A healthy diet and lifestyle adoption with regular physical exercise are also important adjunctive therapeutic modalities, and PAP (either CPAP or bilevel PAP) therapy and pulmonary rehabilitation play critical roles in such patients [7-10].