Following a positive diagnosis, all subjects must have demonstrated clinical improvement and elimination of flow-limitation and sleep EEG disturbances following treatment with continuous positive airway pressure for 3—6 weeks.
Individuals had been recruited from the general population, without sleep complaints and with normal body habitus and normal clinical evaluation. Subjects were retrospectively selected who met the same entry criteria age, BMI and had PSG performed using the same recording protocol. All subjects underwent the same PSG protocol: nocturnal PSG for a minimum of 7 h with lights out at their usual bedtime. These anonymized PSGs are the source of the presented analysis.
This retrospective study, performed on data rendered anonymous prior to analysis, was approved by the Stanford University Medical Institutional Review Board. The detailed algorithm of HHT has previously been well described The essential component of this method is the empirical mode decomposition EMD , which decomposes the target signals into different intrinsic mode functions IMFs. Each IMF is symmetric with 0 mean and the instantaneous phase frequency and amplitudes can be further derived by the Hilbert transform.
The time frequency representation of the signals can be better reconstructed compared to a Fourier-based method. For example, consider a synthetic signal with three wavelets with different frequencies 8, 6, and 5 Hz stitched together; HHT can give a better time and frequency resolution and a more accurate spectrum Figure 1.
In addition, the EMD can sift out the intrinsic undulations at different time scales, thereby preserving the time-varying properties instead of viewing the signal as a summation of infinite sinusoidal oscillations of constant amplitudes and frequencies. For physiological signals, evidence shows that IMFs can usually be associated with a specific physiologic process by matching their temporal frequency distribution to time scales at which specific mechanisms occur, such as respiratory or heart beat components in a blood pressure signal that typically are part of the overall signal 18 , Moreover, to prevent the potential problem caused by intermittent oscillation or perturbations frequently seen in physiological signals, a noise-assisted EMD algorithm 20 was applied to ensure that each IMF did not consist of oscillations at dramatically disparate scales.
It prevented different components from overlapping in the frequency domain, which is, therefore, more appropriate for investigation of physiological signals Also, an orthogonality test was performed between any pair of consecutive IMFs to further verify whether different IMFs are independent to each other.
Figure 1. A A synthetic signal composed by three wavelets with different frequencies stitched together 8, 6, and 5 Hz, respectively. The R to R peaks RR intervals of ECG for each subject were extracted after careful visual inspection and confirmation of the validity of selection by a qualified researcher.
When decomposing the components in the RR intervals, we considered a high-frequency band HF; 0. The respiratory-related IMF of RR the temporal frequencies for its constitutive wavelets are distributed over respiratory frequency was extracted as an instantaneous HF component and the IMFs with the temporal frequencies oscillating among the LF band were merged to represent the sympathetic and parasympathetic activations Figure 2.
In addition, we simultaneously analyzed the respiratory-related elements included in the PPG signals, and we search for the respiratory-related IMF of the PPG signal to further define and quantify the respiratory-related components Figure 2.
Figure 2. The high-frequency HF component respiratory-related fluctuation; black-dashed line and low-frequency LF component dark gray line of the RR interval tracing light gray line as well as the respiratory-related component black of the PPG signals were determined. A transient arousal was noted in associated with the reversal of high respiratory efforts and return to stage 2 NREM sleep was recorded. The respiratory-related oscillations of the RR intervals and PPG signals can be sifted out with high temporal resolution.
The respiratory-related oscillations of the RR intervals and PPG were diminished during arousal-induced central apnea and then returned to higher gain after recovery. In addition, the LF component of the RR intervals was reciprocally increased during arousal.
After defining the oscillations related to specific physiological controls, i. Figure 3. After defining the oscillations related to the respiratory-related RR oscillation [see A ], here, presentation of a 5 min recording with illustration of cycle-based analysis: A 5 min segment of esophageal pressure Pes , RR intervals RR , photoplethysmogramy PPG signal, and nasal flow.
B Identification of corresponding Pes and nasal pressure cycle by cycle and quantification of cycle-based parameters: we obtained a physiologically defined cycle-based analytic tool allowing quantification of the oscillations contained within and extracted from each breath-cycle.
Considering the behavior of the flow curve compared to the behavior of the Pes curve, four main patterns can be identified: Figure 4 shows the raw polysomnographic data in the four different subgroups. However, the progressively more negative Pes peak can also be associated with a decrease in flow i. Figure 4. Raw data of a representative subject during stage 2-NREM sleep with different presentations of the simultaneous esophageal manometry Pes and the nasal flow pressure recordings.
To automatically implement the cycle-based analysis, we considered the difference between the pressures before inspiration to the most negative pressure of the Pes signal as an indicator of respiratory effort for each respiratory cycle. The flow pressure was normalized by dividing the maximal flow pressure during sleep by the flow pressure corresponding to respiratory efforts.
In addition, the normalized flow pressure normalized by dividing each flow pressure by the maximal flow pressure during sleep and the respiratory efforts differences of the peak pressure during normal un-obstructed breathing to the most negative pressure of Pes associated with inspiratory flow limitation were derived.
The normality test was performed on all continuous variables. Otherwise, Wilcoxon rank sum test and non-parameter repeated-measures analysis-of-variance with Tukey-HSD test were computed. A p -value less than 0. All statistics were calculated using the open source statistical program R version 2. As a preliminary calculation, data from 15 patients not involved in the final investigation were analyzed, and sample size was calculated.
The sample size of the studied parameters with a power of 0. Fifty-five PSGs of subjects with well-defined clinical complaints and responding to all inclusion criteria were retrieved and 49 of these PSGs were considered valid for analyses.
Six PSGs showed poor Pes signal quality during analysis of the recordings and were excluded. Nine age-matched control subjects were also retrieved. The demographic and polysomnographic data of the included subjects are summarized in Table 1. Women were predominant in both groups. Table 1. Snoring was present for variable amounts of time during the recording in all subjects with UARS. Although total sleep time was significantly shorter in control subjects, the sleep efficiency and percentage of sleep time spent in stage 3 NREM sleep were markedly decreased in patients with UARS compared to control subjects Table 1.
Pes was significantly more negative and normalized flow was markedly lower during supine compared to non-supine positions in patients with UARS Table 2.
However, none of the derived parameters differed as a result of different sleep positions. In addition, no significant change was found between the first third and the last third of the night. There was no indication of signal drifting during total sleep time. Table 2. Parameters derived from cycle-based analysis during different sleep cycles or positions.
A detailed analysis indicated different findings depending on the above subdivisions in UARS group Table 3. Table 3. Parameters derived from cycle-based analysis in different Pes and flow pressure groups during NREM stage 2.
When looking at indicators of ANS responses, different responses were noted depending on effort. The main finding of this study is that during stage 2 NREM sleep, patients with UARS had higher parasympathetic activity when respiratory efforts were high and inspiratory flow limitation was presented as shown by instantaneous cycle-based analysis of heart rate variability derived from HHT. Disturbances of sleep induced by inspiratory flow limitation can occur without significant oxygen saturation drops, and in the absence of easier to visually scored long EEG-arousals.
The variable "altered nose," which has been used in other studies, 14 This variable was created to differentiate a "normal" nose from a nose with significant alterations in nasal airflow during a typical assessment performed by an otorhinolaryngologist during a consultation. The main criticism of this variable is that this classification is a subjective assessment of nasal patency and may vary between different physicians. Acoustic rhinometry, however, provides an objective assessment of nasal patency, but it is not a commonly used method in clinical practice.
During routine assessment, otorhinolaryngologists use the clinical complaint of nasal obstruction and the physical examination of the nose to help diagnose nasal obstruction, which are the same parameters used in this study.
During the assessment of the two groups, volunteers from the UARS group had a statistically increased frequency of "altered nose" when compared to the control group, i. It is known that not only the alterations detected at the physical examination determine whether or not a patient has nasal obstruction.
These findings should always be correlated with clinical symptoms. In the present study, the group with UARS had more complaints of oropharyngeal dryness than the control group, indicative of oral breathing during sleep. The mouth and oropharyngeal assessment of the study volunteers showed data consistent with the available literature, i.
The investigation of the variable oropharynx alteration in this study showed that both groups had low prevalence of patients with this alteration. This variable, like the altered nose variable, consists in a set of data obtained during the physical examination of the oropharynx, in order to differentiate a normal oropharynx from one disclosing a series of alterations that might be related to SRBD. Regarding the other variables measured in this study, results similar to those described in the literature were observed.
There were no differences regarding gender and socioeconomic distribution when the two groups were compared. When investigating clinical symptoms related to sleep, the authors observed results consistent with characteristics that are well established in the UARS literature, i. The gold standard for RERA detection is measurement of esophageal pressure by an esophageal balloon that shows a progressive increase in negative intrathoracic pressure that culminates in cortical awakening.
This is an invasive and uncomfortable technique, that impairs the onset or maintenance of sleep and, therefore, is not widely used in basal polysomnography literature studies; for these reasons, it was not used in the present study either, which comprises a study limitation.
However, although controversial, some authors maintain that the efficiency of the nasal pressure transducer coupled to the nasal cannula, whether or not associated to a thermistor, may yield a similar result to an esophageal catheter to identify increased respiratory effort and airflow limitation, a technique that is more comfortable and less invasive. Evaluation of nasal prongs for estimating nasal flow.
American Academy of Sleep Medicine. Case book of sleep medicine: a learning companion to the international classification of sleep disorders. Westchester: ASDA; In addition to the study limitation regarding the use of the esophageal balloon, the interpretation and assessment by a physician may introduce a bias. Furthermore, prior to patient assessment, the professionals were trained and familiarized with all the classifications used.
The criteria for UARS definition are still controversial in the literature. The lack of a consensus among researchers creates great difficulty in performing studies involving patients with UARS and, consequently, hinders the advance of knowledge about this disease.
Nevertheless, this study, using a well-defined UARS criterion, involved an otorhinolaryngological assessment carried out in a population sample representative of one of the most important cities in the world.
Therefore, in accordance with these results, the authors believe that, UARS is a multifactorial disease with increased risk of associated comorbidities; however, the nose has a key role in the physiopathology of the disease and should always be thoroughly assessed in a patient diagnosed with UARS. Abrir menu Brasil. Brazilian Journal of Otorhinolaryngology. Abrir menu. E-mail: gregorioluciano me.
Keywords: Sleep disorders; Airway resistance; Nasal obstruction. Introduction Upper airway resistance syndrome UARS was first described in in children and adults as "excessive daytime sleepiness. Standards for staging Sleep was staged according to the criteria proposed by Rechtschaffen and Kales.
The nose was considered obstructed or "altered" in the presence of: Septal deviation grade II or III, or; Septal deviation grade I - nasal obstruction complaint or inferior turbinate hypertrophy, or; Inferior turbinate hypertrophy - nasal obstruction complaint.
References 1 American Sleep Disorders Association. Orofacial-cervical alterations in individuals with upper airway resistance syndrome. Braz J Otorhinolaryngol. Publication Dates Publication in this collection Jul-Aug History Received 28 Mar Accepted 29 May This is an open-access article distributed under the terms of the Creative Commons Attribution License. The sound intensity varies from person to person and is commonly described as a nuisance by a bed partner.
Approximately one out of every two snorers will develop this condition. Although snoring is an indicator for sleep apnea, it is not necessarily experienced by all patients with this disorder. When the snoring and resistance through the airway is significant enough to disrupt the quality of sleep, we call this disorder "Upper Airway Resistance Syndrome" or UARS. In patients with UARS, the sleep quality is generally disrupted to the point of causing clinical consequences such as difficulty initiating or maintaining sleep insomnia , non-refreshing sleep, or excessive daytime sleepiness.
Because of the very brief nature of the many arousals triggered by snoring, patients with UARS are typically unaware of these awakenings and generally do not know that they may be snoring if it were not for the witnessed reports from a bed partner or family member. It is also important to note that not all patients with UARS have audible snoring.
The increased effort to inhale can lead to EEG brain wave arousals and has been referred to in the sleep medicine field as "respiratory effort-related arousals" RERAs. For this reason, an absence of snoring does not imply an absence of obstructive breathing in sleep. Such individuals, however, may have other symptoms such as a dry mouth upon awakening, morning headaches, symptoms of insomnia or daytime sleepiness.
We now believe that UARS represents a progression of disease bridging the transition from "benign snoring" to obstructive sleep apnea. Patients simply do not go to bed normal one night, only to awaken the next morning with obstructive sleep apnea.
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