Response

Dear Editor, We are thankful for the insightful comments and critical evaluation of our study, “Comparing standard treatment of moderate to severe obstructive sleep apnoea to add-on acetazolamide treatment: An open-label randomized controlled trial.” Below, we address the key concerns raised in the letter: PREVIOUS CPAP USE We acknowledge the concern regarding prior continuous positive airway pressure (CPAP) use as a potential confounding factor in AHI reduction. However, we would like to clarify that all participants in both study arms were treatment-naïve and had no prior exposure to CPAP therapy before enrollment. This ensures that the observed differences in AHI reduction were due to the intervention rather than prior CPAP adaptation. BMI AS A POTENTIAL CONFOUNDING FACTOR We recognize that while the overall baseline body mass index (BMI) was statistically comparable between the two groups, there was a slight imbalance in the BMI subgroups (25 kg/m²–29.9 kg/m² and 30 kg/m²–34.9 kg/m²). However, since the primary outcome (Apnea–hypopnea index [AHI] reduction) remained significant despite this distribution, we believe that the impact of BMI on study results was minimal. That said, we agree that a subgroup analysis based on BMI categories or statistical adjustments for BMI could provide additional insights. STATISTICAL VS. CLINICAL RELEVANCE OF AHI REDUCTION We acknowledge that the clinical response to any intervention in obstructive sleep apnea (OSA) is complex and requires long-term studies to fully assess its impact on symptom relief and cardiovascular risk reduction. This limitation was explicitly mentioned in our study. To broaden the impact of acetazolamide beyond AHI reduction, we also assessed other key sleep parameters during the follow-up period, including sleep stage distribution, sleep stage latencies, wake after sleep onset (WASO), cumulative time with oxygen saturation below 90% (T90), and oxygen desaturation index (ODI). These parameters provide a more comprehensive evaluation of acetazolamide’s effect on sleep quality and nocturnal oxygenation, which are crucial in determining its overall therapeutic impact. LACK OF A PLACEBO-CONTROLLED ARM The absence of a CPAP + placebo arm was a recognized limitation of our study. This was due to logistical constraints, but we agree that including a placebo group would have strengthened our ability to differentiate the true pharmacological effects of acetazolamide from potential placebo responses. LONG-TERM SAFETY OF ACETAZOLAMIDE We acknowledge that long-term safety data on acetazolamide in OSA management are lacking. As our study was limited to a 4-week intervention period, we could not evaluate the long-term metabolic effects of acetazolamide. This limitation was mentioned in our study. COMPLIANCE AND ADHERENCE MONITORING As stated in the Methods section of our study, CPAP adherence was objectively monitored using device data usage logs, ensuring precise tracking of therapy compliance. However, acetazolamide adherence was self-reported, which we acknowledge as a limitation. We agree that using more stringent adherence monitoring methods would strengthen the validity of the findings. We appreciate the constructive feedback and recognize the importance of refining study designs for future research. Thank you for your valuable insights.