A prospective observational cohort study to investigate predictors for comorbid insomnia in obstructive sleep apnea (COMISA)

Currently, Continuous Positive Airway Pressure (CPAP) therapy is the treatment
of choice for Obstructive Sleep Apnea (OSA), but a significant percentage of
patients is or becomes non-compliant. It is hypothesized that insomnia may play
a crucial role in CPAP adherence as OSA and insomnia frequently co-exist. This
condition is referred to as comorbid insomnia and OSA: or called COMISA.
However, it remains challenging to predict or diagnose COMISA, since insomnia
complaints can appear minor compared to the OSA complaints, and insomnia can be
masked by sleep fragmentation caused by obstructive events. Additionally,
somnological expertise to diagnose insomnia in the presence of external sleep
disruptors may be lacking. The diagnosis of insomnia relies on subjective
assessments of sleep quality and complaints, while the diagnosis of OSA is
based on a single-night polysomnography (PSG) measurement. However, long-term
sleep measurements could play a pivotal role in obtaining more insight in a
patient*s sleep pattern.
This prospective study will focus on phenotyping patients suspected of OSA,
using PSG measurements and modern unobtrusive home-assessment techniques to
evaluate both objective and subjective sleep.

To identify characteristics of comorbid insomnia in patients with OSA as a
factor for predicting CPAP compliance.

To answer this, the aim can be divided into three parts with corresponding
research questions.

Part 1: Identification of COMISA subtypes
Question 1a. Is it possible to recognize and identify COMISA subtypes?


Part 2: Prediction of comorbid insomnia in patients suspected for OSA.
Question 2a. Which parameters predict an (*Overt*) COMISA diagnosis in patients
suspected for OSA before treatment?
Question 2b. Which parameters predict a change from an initial pre-treatment
diagnosis OSA towards a final diagnosis of (*Masked* or *Induced*) COMISA after
treatment with CPAP?

Part 3: Prediction of CPAP compliance in patients (initially) diagnosed with
OSA or COMISA.
Question 3a. Which parameters predict whether a patient will be compliant to
CPAP or not?

Prospective observational cohort study, in patients referred for suspected OSA
to the Amphia sleep center, a large second-line facility for sleep disorders.
For this population, normal routine clinical investigation includes ambulatory
PSG and assessment of daytime sleepiness using the Epworth Sleepiness Scale
(ESS) questionnaire. The treating physician will make a diagnosis according to
this clinical information and a clinical interview.
Participants of the study will receive standard clinical care according to the
procedure above.

As part of the study, three types of measurements will be added.
1. Wrist-worn photoplethysmography (PPG) measurements will be performed at home
during the night, for two weeks. The aim of this measurement is to obtain
objective heart rate variability (HRV) measurements on which sleep staging can
be performed, yielding insight in long-term sleep patterns and night-to-night
variability.
2. An electronic version of a sleep diary will be kept for two weeks (during
the same weeks as the PPG measurements). Electronic versions enable us to
derive sleep parameters automatically and to compare these subjective results
with the objective results from PPG measurements.
3. Digital questionnaires will be completed to obtain subjective information to
assess day- and nighttime complaints, anxiety and depression symptoms, sleep
quality and nocturnal arousals..

If patients are diagnosed with OSA or COMISA ánd receive CPAP-therapy as part
of their treatment, both wrist-worn PPG measurements and sleep diary will be
repeated for two weeks after ten weeks of treatment. In addition, the Insomnia
Severity Index (ISI) questionnaire and and the Epworth Sleepiness Scale (ESS)
questionnaire will be completed for a second time to assess day- and nighttime
components of insomnia and daytime sleepiness after treatment.

There are no direct clinical benefits for the subjects, but it is expected that
the measurements and analysis will reveal characteristics of comorbid insomnia
in OSA to predict CPAP compliance. This may contribute to enhance methods for
diagnosis and appropriate treatment in this highly prevalent comorbid disorder.
The burden for participants is limited, since an unobtrusive wearable, a simple
sleep diary and questionnaires will be used for the study. Further,
participants will undergo routine clinical investigation.