Thank you. I am sorry for the delay in responding. Do I understand correctly that the current differential diagnosis for the symptoms suggestive of obstructive sleep apnoea or hypopnoea is:
- No obstructive sleep apnoea or hypopnoea (Evidence: AHI <5 events per hour)
- Obstructive sleep apnoea or hypopnoea: (Evidence: AHI >4 events per hour)
- Other possible diagnoses
Are you are suggesting that there should be a more detailed differential diagnosis (with addition of the sentences in italics) to avoid missing Arousal Failure with recovery and Arousal and Recovery failure?:
- No sleep apnoea or hypopnoea (Evidence: AHI <5 events per hour but no prolonged apnoea pattern of arousal failure)
- Sleep apnoea or hypopnoea with: [A] Repetitive Reduction in Airflow / RRA (Evidence: AHI >4 events per hour without prolonged apnoea pattern of arousal failure) or (B) Arousal failure with recovery or (Evidence: AHI >0 of latter events of prolonged apnoea per hour) or (C) Arousal and recovery failure (Evidence: AHI >0 of latter events of very prolonged apnoea per hour)
- Other possible diagnoses
Some points:
- The treatment for RRA is an oral device or CPAP, weight reduction, etc. Should the treatment for Arousal Failure with recovery and Arousal and Recovery Failure be expected to be the same as for RRA?
- Do we know from observational studies how prevalent Arousal Failure with recovery and Arousal and Recovery Failure is in patients with symptoms suggestive of obstructive sleep apnoea or hypopnoea when the AHI is <5 events per hour and the AHI is > 4 events per hour? Is it possible to suspect Arousal Failure with recovery and Arousal and Recovery Failure clinically (e.g. with additional evidence of neurological dysfunction)?
- In order to establish the threshold for AHI where treatment for RRA provides a probability of benefit, I would do a study to estimate the probability of symptom resolution in a fixed time interval at different AHI values with no treatment or sham treatment (presumably a zero probability at all AHI values on no treatment) and on treatment. This might be done by fitting a logistic regression function or some other model to the data on treatment and on no treatment (when the curve might be zero for all values of AHI) and on treatment (when the probability of symptom resolution should rise as the AHI rises). Treatment should then be considered where the latter curve appears to rise above zero. This rise above the control curve may well happen at an AHI of 5 events per hour, or above or below 5 events per hour (e.g. 3 events per hour). This would be an approach setting a threshold based on evidence (as opposed to consensus guesswork).
- The above would apply to ‘RRA Obstructive Sleep Apnoea / Hypopnoea’. However for Obstructive Sleep Apnoea / Hypopnoea with Arousal Failure with recovery and Arousal and Recovery Failure the curve might be different with perhaps a clear probability of benefit at any AHI > 0. Note therefore that there may be a number of different AHI treatment indication thresholds created by a study of this kind. The symptoms alone might provide criteria for a diagnosis of ‘Clinical Obstructive Sleep Apnoea / Hypopnoea’, but for a ‘physiological’ diagnosis there may be 3 different criteria for (i) RRA, (ii) Arousal Failure and (iii) ‘Arousal and Recovery Failure. Each of these would also be sufficient to diagnose ‘Physiological Obstructive Sleep Apnoea / Hypopnoea’ (i.e. each might be a ‘sufficient’ criterion for the diagnosis) as well as prompting the doctor to offer treatment options. However, the probability of benefit from each treatment based from the logistic regression curve based on the AHI as a measure of disease severity and the adverse effects of treatment would have to be discussed with the patient during shared decision making.
- Although I consider Sleep Apnoea / Hypopnoea in my differential diagnoses in internal medicine and endocrinology and have some understanding of its investigation and management, I have never personally conducted Polysomnography or personally treated patients with CPAP etc., so please correct any misunderstandings. However, based on my work of trying to improve diagnostic and treatment indication criteria in endocrinology, the above is how I would approach the problem for Sleep Apnoea / Hypopnoea. I agree with you that this is a problem that needs close collaboration between clinicians and statisticians. The advice of statisticians such as @f2harrell or @stephen or someone similar in your area would be essential. I think that this type of work to improve diagnosis and treatment selection criteria is a huge growth area for future close collaboration between clinicians and statisticians. I am trying to encourage students and young doctors (and their teachers) to do this in the Oxford Handbook of Clinical Diagnosis, especially in the forthcoming 4th edition.