A comparison of inspiratory airflow dynamics during sleep between upper airway resistance syndrome patients and healthy controls, 2013, Gold et al.

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A comparison of inspiratory airflow dynamics during sleep between upper airway resistance syndrome patients and healthy controls
Avram R. Gold, Joan E. Broderick, Morris S. Gold & Mohammad M. Amin
https://www.researchgate.net/publication/235620968_A_comparison_of_inspiratory_airflow_dynamics_during_sleep_between_upper_airway_resistance_syndrome_patients_and_healthy_controls (PDF available)

Objectives: A test of the hypothesis that upper airway resistance syndrome (UARS) patients have an increased prevalence of inspiratory airflow limitation (IFL) during sleep compared to healthy controls.

Methods: We compared inspiratory airflow dynamics during sleep between 12 UARS patients (nine females and three males) and 12 healthy controls matched for age, gender and obesity with maximal age limited at 45 years. A standard clinical polysomnogram (airflow measured with a nasal/oral pressure catheter) was performed to assess the impact of SDB on the participants' natural sleep. A second full-night polysomnogram with a pneumotachograph and a supraglottic pressure catheter to measure airflow and effort was performed to compare the maximal inspiratory airflow and effort and the percentage of flow-limited breaths during supine, continuous stage 2 sleep between groups.

Results: During clinical polysomnography, UARS participants did not differ significantly from controls in sleep architecture or fragmentation. We observed a small difference in apnea hypopnea index between UARS participants and controls (1.6 ± 1.9 vs. 0.4 ± 0.3, respectively; p = 0.035). During supine, continuous stage 2 sleep, 64.2 % (35.8; mean (SD)) of UARS participants' breaths were flow-limited compared with 34.0 % (39.3) of controls' breaths (p = 0.06). The groups did not differ in maximal inspiratory airflow or inspiratory effort.

Conclusions: Our findings indicate a less-than-robust difference in respiratory parameters during sleep between UARS patients and healthy controls and no difference in standard sleep parameters or sleep fragmentation. We consider a pathophysiology of UARS that incorporates these findings.

 

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Participants:

UARS was diagnosed in patients at the Stony Brook University (SBU) Sleep Disorders Center who (1) complained of sleepiness or fatigue (without symptoms of narcolepsy), (2) had an apnea hypopnea index (AHI) below 10 events/h, (3) with IFL during NREM sleep evident by nasal/oral pressure measurement and (4) fewer than two REM onsets during a four-nap multiple sleep latency test performed the day following their polysomnogram (the clinical criteria for narcolepsy of the SBU Sleep Disorders Center).

In their initial phone screens, the 12 UARS participants were characterized by the symptoms associated with CSS [central sensitization syndromes]. Two complained of chronic joint and muscle pain, three complained of chronic low back pain, one had chronic pelvic pain, four had pre-menstrual syndrome, one had temporomandibular joint syndrome, one had IBS, seven complained of chronic fatigue, three complained of chronic insomnia and three complained of chronic hyperventilation or dizziness. None of the healthy controls had any of these symptoms/syndromes as they were reasons for exclusion from participation (Table 1)

All participants underwent two polysomnograms (PSGs). Prevalence of inspiratory flow limitation (IFL) was obtained during the second PSG where a supraglottic catheter was used to measure respiratory effort (IFL can be inferred from a nasal pressure transducer signal, but technically the definition of IFL requires that the plateau in airflow is accompanied by increasing respiratory effort, which requires an esophageal/supraglottic catheter to measure). For 3 of the UARS participants, there were problems with the supraglottic catheter signal (related to drying of the catheter tip or mucous), so IFL was inferred from airflow tracings alone ("The Cohen’s kappa statistic [0.62] we obtained suggests there was a good correlation of our two methods for determining IFL.")

Re: the fact that 2 UARS subjects had 0%/close to 0% IFL (during the PSG with the supraglottic catheter), it was discussed that they had significant IFL (based on airflow tracings) during the PSG without the catheter, and that the catheter may actually prevent upper airway collapse in some individuals:

A most puzzling observation in this study concerns UARS participants #1 and #3, who had almost no flow-limited breaths during supine, uninterrupted stage 2 sleep (3.7 % and 0 %, respectively; Table 5). Although the absence of IFL during supine stage 2 sleep could have been a sampling artifact (only the first 6 min of continuous stage 2 sleep was analyzed), consideration of their respiratory profiles over the entire night showed little or no prevalence of IFL at any time. Rather, in these two UARS participants we observe a difference between the prevalence of IFL in the presence of the supraglottic catheter during the second PSG compared to the first PSG during which there was no supraglottic catheter. In both participants, during the first PSG, we observed frequent flow-limited breaths during continuous stage 2 sleep (Fig. 3). A similar phenomenon was observed in our previous study of inspiratory airflow dynamics during sleep among females with IBS [6]. In that study, three of 12 female IBS participants, all of whom were lean, had 0 % flow-limited breaths during supine stage 2 sleep on the night with the supraglottic catheter, while demonstrating considerable IFL, and even apnea, during the un-instrumented night. Similarly, UARS participants #1 and #3 in this study were females with low BMI (22.5 and 21.9 kg/m2, respectively; Table 2). Thus, it is possible that the presence of a supraglottic catheter affects inspiratory airflow dynamics during sleep in lean females with IBS and UARS.

Notably, multiple asymptomatic controls had significant inspiratory flow limitation (IFL) during the sampled breaths (and 3/12 had >90% IFL). So clearly IFL alone is not enough to cause problems, even though large-scale data show that increased IFL is associated with self-reported sleepiness and psychomotor vigilance task lapses (and sleep medicine's earliest epidemiological studies showed that snoring [a proxy for IFL] is associated with self-reported sleepiness independent of OSA [most people with OSA snore]):

Flow Limitation Is Associated with Excessive Daytime Sleepiness in Individuals without Moderate or Severe Obstructive Sleep Apnea, 2024, Mann et al.
Increased Flow Limitation During Sleep Is Associated With Increased Psychomotor Vigilance Task Lapses in...Suspected OSA, 2024, Staykov et al.

This is where Dr. Gold's paradigm of UARS/OSAS comes in (sensitization/stress response to IFL - see AI summary here), providing a potential explanation for how IFL could be driving these (and other) symptoms in sleep-disordered breathing patients, even though many asymptomatic people have significant IFL.

So you may be wondering, how can we know that UARS was even the cause of these specific patients' fatigue/sleepiness (/other symptoms) in this study? Well, technically we can't (it would require a sham-controlled CPAP treatment trial to adequately prove that to people's satisfaction). But to see some of the evidence for CPAP improving fatigue and other symptoms in sleep-disordered breathing patients:

The effect of nasal continuous positive airway pressure on the symptoms of Gulf War illness, 2011, Amin et al
Somatic arousal and sleepiness/fatigue among patients with sleep-disordered breathing, 2016, Gold et al.