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obstructive sleep apnea diagnosis References

Diego Munduruca Domingues , Paloma Rodrigues Rocha, Ana Cláudia M. V. Miachon, Sara Quaglia de Acknowledgements

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Abstract
The aim of this study was to build and validate an artificial neural network (ANN) algorithm to
predict sleep using data from a portable monitor (Biologix system) consisting of a high-
resolution oximeter with built-in accelerometer plus smartphone application with snoring
recording and cloud analysis. A total of 268 patients with suspected obstructive sleep apnea
(OSA) were submitted to standard polysomnography (PSG) with simultaneous Biologix (age:
years; body mass index: , apnea-hypopnea index [AHI]:
events/h). Biologix channels were input features for construction an ANN model to predict
sleep. A k-fold cross-validation method (k=10) was applied, ensuring that all sleep studies
(N=268; 246,265 epochs) were included in both training and testing across all iterations. The
final ANN model, evaluated as the mean performance across all folds, resulted in a sensitivity,
specificity and accuracy of 91.5%, 71.0% and 86.1%, respectively, for detecting sleep. As
compared to the oxygen desaturation index (ODI) from Biologix without sleep prediction, the
bias (mean difference) between PSG-AHI and Biologix-ODI with sleep prediction (Biologix-
Sleep-ODI) decreased significantly (3.40 vs. 1.02 events/h, p<0.001). We conclude that sleep
prediction by an ANN model using data from oximeter, accelerometer, and snoring is accurate
and improves Biologix system OSA diagnostic precision.

Introduction
Obstructive sleep apnea (OSA) is characterized by repetitive episodes of upper airway
obstruction, resulting in sleep fragmentation and oxygen desaturation1. OSA is associated
with several health consequences, including poor sleep quality, excessive daytime sleepiness,
and increased cardiovascular risk2. Polysomnography (PSG) is considered the gold standard
method for OSA diagnosis3. However, PSG is expensive and inconvenient for patients3.
Portable monitoring (PM) is a simplified method that has been validated for OSA diagnosis4.
In contrast to PSG, PM does not detect sleep. The consequence of this limitation is that the
number of respiratory events in PM devices are reported by hour of monitoring rather than
hours of sleep. Therefore, the absence of sleep monitoring is a potential source of variability
between PSG and PM. Biologix system is a new PM device based on a high-resolution
wireless oximeter ( , Biologix Sistemas S.A., Brazil) with built-in accelerometer and
a smartphone application (app) that is downloaded to the patient’s smartphone. The app
records snoring, and all information is automatically processed in the cloud. Biologix system
has been validated for OSA diagnosis against PSG in the sleep laboratory5 and against
traditional PM at home6. However, Biologix system does not monitor sleep and therefore
reports oxygen desaturation index (ODI) based on hours of monitoring rather than hours of
sleep. Therefore, the objective of this study was to build and validate an artificial neural
network (ANN) algorithm using data from oximeter, accelerometer and snoring to detect
sleep. We also tested the hypothesis that ANN model improves the Biologix system OSA
diagnostic precision.

Methods
Patients and data collection
The study included patients recruited in the validation study of the Biologix system against
PSG. Full details of the protocol have been published elsewhere5. The local ethics committee
(Comissão de Ética para Análise de Projetos de Pesquisa do HCFMUSP - CAPPesq) approved
the protocol (SDC 4515/17/015), and all patients gave their informed consent. The study has
been performed in accordance with the Declaration of Helsinki. Briefly, we studied patients
with suspected OSA referred for overnight-laboratory PSG at the Sleep Laboratory of the
Heart Institute (InCor).

PSG included recording of the electroencephalogram (EEG) central (C) and occipital (O)
channels referred to the auricular channel (A) (C3/A2, C4/A1, O1/A2, O2/A1), electrooculogram
(EOG), submental electromyogram (EMG), left and right anterior tibialis EMG,
electrocardiogram, thoraco-abdominal effort, oronasal airflow (thermistor and nasal pressure
based airflow measurement), oxygen saturation ( ) with pulse oximetry, and body
position (EMBLA S7000, Embla Systems, USA and Alice 5, Respironics Inc., USA)5. Two
certified technicians independently analyzed all PSG studies. Hypopnea was defined as a
drop in the peak signal excursion of 30% from the pre-event baseline nasal pressure signal
lasting for at least 10 seconds. Respiratory events were scored according to the American
Academy of Sleep Medicine criteria ( 3% reduction in from the pre-event baseline or
an event associated with arousal). OSA was classified based on current standards as follows:
absence of OSA (AHI < 5 events/hour), mild OSA (5 AHI < 15 events/hour), moderate OSA
(15 AHI < 30 events/hour), and severe OSA (AHI 30 events/hour).

Simultaneously, the patients also wore a high-resolution oximeter ( , Biologix

Sistemas S.A., Brazil) with built-in accelerometer linked by Bluetooth to a smartphone app
that recorded snoring. The firmware captures data at a rate of 100 samples per
second, providing beat-to-beat raw measurements with a precision of 0.1%. To
smooth the data, a moving average over 4 heartbeats was applied. Oxygen desaturations are
calculated providing the ODI. The ODI was calculated as the number of desaturations (
reduction in ) per hour, using either total recording time or total sleep time. The
oximeter information was sent to the cloud, and automatically analyzed (Fig. 1). The PSG and
Biologix data were time-synchronized.

Fig. 1

Biologix system. The wireless oximeter connects via Bluetooth to the smartphone’s Biologix
application. The data is sent to the cloud and automatically analyzed by the algorithm.

Full size image

ANN algorithm
ANN are algorithms based on the biological structure of the human brain, in which several
neurons are connected7,8. These neurons are divided into at least three layers: inputs, a
variable number of hidden layers, and outputs. Each of these layers is connected to the next
layer by an activation function, a weight associated with its signal, and a bias8. To build and
validate our ANN algorithm, we used data derived from the Biologix system including oximeter
( , heart rate [HR]), with built- in accelerometer (movement), and smartphone app
(snoring). Snoring was obtained by recording the audio of the environment performed by the
smartphone app and processed by another neural network. This algorithm provides a binary
output indicating whether the patient is snoring or not during the audio recording stretches,
similar to other approaches found in the literature9. The k-fold cross-validation method (k=10)
was used to build and validate the ANN algorithm10,11. The sleep studies were randomly
divided into 10 folds, with each fold used for cross-validation to ensure that all studies were
both trained and tested across multiple iterations. In each fold, the training and test datasets
were employed to optimize the weights and biases, reducing the error between the predicted
value by the neural network results. The gold standard for sleep classification was a binary
variable (sleep or awake) determined by PSG epochs of 30 seconds. The process starts with
a forward pass for initial values of weight and bias and for pre-defined activation functions.
Outputs are then calculated, and errors are determined. In the next step, the values of
weights and biases are redefined through a process called backpropagation12. Using the
newly calculated values, the process is redone. This occurs recursively until a maximum
number of iterations8,13. Our model consists of an input layer, one hidden layer and an output
layer. The input layer has 97 neurons, the hidden layer has 128 neurons and a ReLU (rectified
linear unit)14 activation function. Finally, the output layer has 1 neuron and a sigmoid
activation function (Fig. 2). In order to test the accuracy of the accelerometer alone in
predicting sleep, another ANN model was built using only the accelerometer channel, with 23
neurons in the input layer, while the other layers remained the same.

Fig. 2

Artificial neural network algorithm diagram. The 97 input features were extracted from the channels,
processed by the hidden layer with 128 neurons, resulting in a single neuron output that predicted
whether the patient was sleep or awake. oxygen saturation, ReLU rectified linear unit.

Full size image

Features
The first step was the treatment of missing values (less than 1% of the data was missing),
which consisted of replacing these values by zero, in the case of the accelerometer, and by
the maximum values for the cases of and HR. Subsequently, the features were
calculated using epochs of 30-seconds synchronize to PSG epochs. The features used in the
model were calculated based on the signals obtained by the Biologix system and included
, HR, movement detected by the accelerometer, and snoring detected by the
smartphone app. The features were: (1) presence or absence of oxygen desaturation,
expressed as a binary variable; (2) desaturation range; (3) quartile (75th) as a measure
of the tendency of the patient’s values during sleep. The HR signal provided several
features: (1) average pulse interval; (2) standard deviation of HR; (3) HR variability (HRV) time
domain features (SDNN, RMSSD, PNN50, SD1, SD2); (4) HRV frequency domain features (LF
power, HF power, LF/HF ratio). The accelerometer data generated multiple features: (1)
variance; (2) root mean square (RMS); (3) skewness; (4) kurtosis. Other variables of interest
associated with snoring, obtained by the Biologix app, were also used, which improved the
performance of the machine learning model. In addition, some of these features were
considered shifted in relation to the current time step for the better composition of the
predictive model, totaling 97 inputs for the neural network model summarized in the Table 1.
Finally, the data was standardized by removing the mean and scaling to unit variance15,16.

Where u is the mean value, s is the standard deviation, x is the samples and z is the new
samples15,16.

Table 1 Features inputted into the ANN algorithm with all Biologix channels.

Full size table

Statistical analysis
Accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value
(NPV), Cohen’s kappa coefficient ( ), F1-score (weighted average between the precision
score [PPV] and recall score [sensitivity]), and area under the curve (AUC) were calculated
for evaluation of the ANN model. Because several previous studies used only accelerometer
data to predict sleep, we used the McNemar’s test17 to compare the ANN performance to
predict sleep using only accelerometer data with ANN performance using all Biologix
channels (SpO2, HR, accelerometer, and snoring). Overall summary statistics were calculated
in terms of means and standard deviations for continuous variables and counts and
percentages for categorical variables. Shapiro-Wilk test was used for checking the data
normality of the PSG and the Biologix system. Since the data distribution was not normal and
they were not independent, the differences were analyzed by the Wilcoxon signed-rank test.
In addition, we calculated the sensitivity, specificity, accuracy, PPV, and NPV of the Biologix
system, without and with sleep prediction, versus PSG, in the detection of OSA severity. Mc
Nemar’s test17 compared the Biologix system performance without and with sleep prediction.
Finally, to assess the amount of agreement on OSA diagnosis between PSG-AHI and Biologix-
ODI, without and with sleep prediction, Bland-Altman plots were performed. RStudio
2023.06.1 software (R Foundation for Statistical Computing) was used for all statistical
analysis. Significance was assessed with a p-value .

Results
Out of 304 consecutive patients previously evaluated to validate the Biologix system against
PSG5, 268 had snoring recordings and were used for this study. The patients had typical
characteristics of patients referred for OSA diagnosis, and were predominantly obese middle-
aged adults, with comorbidities and with a high proportion of moderate to severe OSA (Table
2). As described in the method section, the sleep studies underwent 10-fold cross-validation.
Each fold consisted of a training set of 90% of the patients (approximately 241 patients,
corresponding to 221,639 epochs) and a test set of 10% of the patients (approximately 27
patients, corresponding to 24,627 epochs).

Table 2 Demographic and sleep data of the population studied.

Full size table

The total sleep time determined by PSG and by the Biologix ANN model using all channels
was similar ( min vs. min, respectively, p=0.15), as well as sleep
efficiency ( % vs. %, respectively, p=0.15). Table 3 shows the
performance metrics of the ANN model using only the accelerometer and the ANN model
using all Biologix channels to predict sleep, as assessed by k-fold cross-validation. The
performance of the ANN when all Biologix channels were used was significantly higher than
when only accelerometer data was used (p ), as revealed by McNemar’s test. The
ANN model using data from all Biologix channels achieved higher AUC values of the receiver
operating characteristic (ROC) curve, indicating superior performance in predicting sleep
(Fig. 3).

Table 3 Performance assessment of the ANN models to predict sleep.

Full size table

Fig. 3

Receiver operating characteristic (ROC) curve. The ROC curve for the ANN using only the
accelerometer and the ANN using all Biologix channels ( , HR, accelerometer, and snoring).

Full size image

The ability to predict sleep was evaluated for its impact on OSA severity determination. AHI
was classified using cut-offs of 5, 15, and 30 events/h. We calculated the specificity,
sensitivity, accuracy, PPV, and NPV of the Biologix system, without and with sleep prediction
(Table 4). Compared to Biologix-ODI, the specificity to predict OSA as defined as AHI 5 or
15 events/h increased with sleep prediction, however, the improvement did not reach
statistical significance.

Table 4 Diagnostic performance of Biologix system without and with sleep prediction
in OSA severity determination.

Full size table

Bland-Altman analysis between PSG-AHI versus Biologix-ODI showed that the limits of
agreement were similar without and with sleep prediction ([-20,27] vs. [-20,22], respectively),
whereas the bias (mean difference) decreased significantly with sleep prediction (3.40 vs.
1.02, p ) (Fig. 4a and b).

Fig. 4

Bland-Altman plots for PSG-AHI and Biologix-ODI. (a) Bland-Altman plot for PSG-AHI and Biologix-
ODI without sleep prediction. (b) Bland-Altman plot for PSG-AHI and Biologix-Sleep-ODI with sleep
prediction. AHI apnea-hypopnea index, PSG polysomnography, ODI oxygen desaturation index
considering total recording time, Sleep ODI oxygen desaturation index considering total sleep time.

Full size image

Discussion
In the present study, we built and validated a new algorithm to predict sleep based on the
ANN model using data derived from the Biologix system, including a high-resolution oximeter
with built-in accelerometer, and snoring detected by the smartphone with the Biologix app.5,6.
Firstly, the algorithm exhibited good performance in distinguishing sleep from awake, with a
sensitivity of 91.5%, specificity of 71.0%, accuracy of 86.1%, Cohen’s kappa coefficient of
0.60, F1-score of 0.90, and AUC of 0.90. Secondly, the algorithm performance to predict
sleep was better using all Biologix channels compared to using only the accelerometer
channel. Thirdly, Biologix system with sleep prediction decreased the bias between PSG-AHI
and Biologix-ODI.

PM has been validated to detect OSA18,19. However, in contrast to PSG, PM does not
discriminate wakefulness from sleep. In this context, several studies have attempted to
predict sleep using a binary classification (sleep versus wakefulness) mainly using actigraphy.
Overall, actigraphy is recognized as an accurate and sensitive method to detect sleep
periods, but with poor specificity to identify wakefulness (ranging from 32 and 61%)20,21,22. A
study carried out with 8 commercial sleep tracking devices, showed that the sensitivity to
detect sleep, as compared to PSG, was very high (all greater than or equal to 93%). However,
the specificity for predicting sleep was variable and generally low, ranging from 18 to 54%23.
Alternatively, algorithm models based on data from several channels, either isolated or in
combination, including accelerometer, respiratory signals, breathing sounds, and HRV, have
been used in an attempt to improve sleep/wakefulness detection by
PM22,24,25,26,27,28,29,30,31. For instance, Dafna et al.26 developed and validated an algorithm
for detecting sleep periods in patients with OSA based on the analysis of respiratory sounds.
Despite the high sensitivity of 92.2%, the specificity to detect wakefulness was low (56.6%).
In turn, Montazeri et al.32 reported promising results with a sensitivity of 87.8%, specificity of
71.4%, and accuracy of 82.3% to detect sleep using an algorithm model based on tracheal
sound and movement data recorded with a small wearable device attached over the trachea.
The reported device is also able to predict the AHI based on tracheal sounds, however, it
does not measure . In general, the main challenge of all systems that do not measure
EEG is to achieve high sensitivity to detect sleep while also maintaining reasonable specificity.
To address this challenge, our algorithm combines built-in accelerometer data with other
variables, including , HR, and snoring. As compared to the ANN algorithm using only
the accelerometer, the ANN algorithm using all channels had a better performance in
detecting sleep. Specifically, the specificity increased from 65.4% to 71.0%, without
compromising sensitivity (91.7% vs. 91.5%, respectively), resulting in an increase of the
accuracy (84.5% vs. 86.1%). In addition, the AUC increased from 0.88 to 0.90, indicating a
greater ability to discriminate between sleep and wakefulness when all Biologix channels were
used.

Compared to PSG-AHI, Biologix-ODI with sleep prediction (Biologix-Sleep-ODI) improved the

performance of Biologix-ODI.The Bland-Altman plots (Fig. 4) showed a significant decrease in
the bias between PSG-AHI and Biologix-ODI when sleep prediction was taken into
account (Biologix-Sleep-ODI). As compared to Biologix-ODI, the specificity to predict OSA as
defined as AHI 5 or 15 events/h increased with sleep prediction (Biologix-Sleep-ODI),
however, the improvement did not reach statistical significance (Table 4).

Despite the strengths, our study has limitations. Firstly, the number of patients was relatively
small. On the other hand, because sleep prediction was based on 30-second epoch, the
study used a large data set to build an algorithm to predict sleep. Secondly, the study was
carried out using data from patients with suspected OSA, so the accuracy of our ANN model
to predict sleep in healthy subjects may be different. Another caveat is that in contrast to
wrist actigraphy, Biologix built-in actigraphy is placed on the finger. Although we have no
reason to believe that there is a substantial difference between wrist and finger movements,
we acknowledge that this comparison was not performed.

Conclusion
In conclusion, we showed that an algorithm based on ANN using all Biologix channels,
including , HR, accelerometer, and snoring is able to detect sleep with a good accuracy.
Sleep prediction resulted in a reduction in the bias between PSG-AHI and Biologix-Sleep-ODI.

Data availability
The data that support the findings of this study are available from Biologix Sistemas S.A., but
restrictions apply to the availability of these data, which were used under license for the
current study and are not publicly available. Data are, however, available from the authors
upon reasonable request and with the permission of Biologix Sistemas S.A.

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Acknowledgements
Sleep laboratory of the Heart Institute (where PSG were performed), study participants and
each coauthor are acknowledged.

Author information
Authors and Affiliations
Biologix Sistemas S.A., São Paulo, SP, Brazil
Diego Munduruca Domingues, Paloma Rodrigues Rocha, Ana Cláudia M. V. Miachon & Filipe
Soares

Laboratório do Sono, LIM 63, Divisão de Pneumologia, Instituto do Coração, InCor,

Hospital das Clínicas HCFMUSP, Universidade de São Paulo, Eneas de Carvalho Aguiar
44, 8º andar, São Paulo, SP, 05403-900, Brazil
Sara Quaglia de Campos Giampá, Pedro R. Genta & Geraldo Lorenzi-Filho

Contributions
D.M.D., A.C.M.V.M., and F.S. led the development and validation of the artificial neural network
algorithm. D.M.D and P.R.R. analyzed the results. D.M.D, P.R.R, A.C.M.V.M., S.Q.C.G and G.L.F
wrote the initial manuscript draft with input from all authors. P.R.G contributed substantially to
the data analysis, interpretation of the data, or a combination thereof. All authors reviewed the
manuscript.

Corresponding author
Correspondence to Diego Munduruca Domingues.

Ethics declarations
Competing interests
Authors Diego Munduruca Domingues, Paloma Rodrigues Rocha, Ana Cláudia M. V. Miachon
and Filipe Soares are employees of Biologix. Geraldo Lorenzi-Filho is co-founder of Biologix.
This research was funded by Biologix Sistemas S.A., Brazil.

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Domingues, D.M., Rocha, P.R., Miachon, A.C.M.V. et al. Sleep prediction using data from
oximeter, accelerometer and snoring for portable monitor obstructive sleep apnea
diagnosis. Sci Rep 14, 24562 (2024). https://doi.org/10.1038/s41598-024-75935-8

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Keywords
Artificial neural network Sleep prediction Obstructive sleep apnea

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