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Background: Negative airway pressure loading such as seen during obstructive apnea/hypopnea may influence upper airway (UA) mechanical properties. We measured the effects of such loading on UA mechanical properties during wakefulness and assessed the potential link with night-time apnea worsening., Methods: Twitch stimulations of the phrenic nerve were applied before and after a step-by-step increase in UA suction flow in 10 sleep apnea and 10 control males., Results: Inspiratory closing pressure was lower in control than in apneic subjects. No consistent changes were observed in UA mechanical properties before and after the trial. In apneic patients, changes in the apnea index from the beginning to the end of the night correlated with changes in inspiratory closing pressure following suction flow., Conclusion: (1) Apnea phenotype does not influence the impact of negative airway pressure on UA dynamic properties during wakefulness and (2) worsening of sleep apnea frequency during the night may relate to the exposure to recurrent UA negative pressure., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Phrenic nerve magnetic stimulation (PNMS) performed anterolaterally at the base of the neck (BAMPS) and cervical magnetic stimulation are common techniques for assessing upper airway (UA) mechanical properties in conscious humans. We considered that if NMS performed at the sternal level (a-MS) could induce a similar percentage of flow-limited twitches as BAMPS in conscious subjects, gauging UA dynamic properties by PNMS would be simplified. Instantaneous flow, pharyngeal and esophageal pressures, as well as thoraco-abdominal motion were recorded in 10 conscious sleep apnea patients. BAMPS and a-MS were applied at end expiration. The percentage of flow-limited twitches, maximal tolerated intensity, and minimal stimulator output associated with flow-limited twitches were similar between BAMPS and a-MS. Examining the effects of stimulation site, stimulation intensity and site*intensity interaction on the characteristics of flow-limited twitches, the former was responsible for more negative peak esophageal pressure (BAMPS: -11.5 ± 0.9 cmH(2)O; a-MS: -6.5 ± 1.1 cmH(2)O; P = 0.002) and UA closing pressure (BAMPS: -7.7 ± 0.5 cmH(2)O; a-MS: -5.8 ± 0.6 cmH(2)O; P = 0.02) as well as for lower mean linear upper airway resistance (UAR) (BAMPS 3.5 ± 0.4 cmH(2)O·l(-1)·s(-1); a-MS 2.2 ± 0.4 cmH(2)O·l(-1)·s(-1); P = 0.02). a-MS systematically evoked outward/inward thoracic displacement, although this movement pattern was observed in only 50% of patients when they were subjected to BAMPS. Linear UAR of BAMPS-induced flow-limited twitches was lower in the presence of initial outward thoracic movement (2 ± 0.05 cmH(2)O·l(-1)·s(-1)) than with inward motion (4.3 ± 1.5 cmH(2)O·l(-1)·s(-1); P = 0.03). We conclude that a-MS represents a practical and functional technique to evaluate UA mechanical properties in conscious sleep apnea patients.

Rationale: Functional interaction between upper airway (UA) dilator muscles and the diaphragm is crucial in the maintenance of UA patency. This interaction could be altered by increasing respiratory drive. The aim of our study was to compare the effects of hypercapnic stimulation on diaphragm and genioglossus corticomotor responses to transcranial magnetic stimulation (TMS)., Methods: 10 self-reported healthy men (32 ± 9 yr; body mass index = 24 ± 3 kg/m(-2)) breathed, in random order, room air or 5% and then 7% Fi(CO(2)), both balanced with pure O(2). Assessments included ventilatory variables, isoflow UA resistance (at 300 ml/s), measurement of lower chest wall/diaphragm (LCW/diaphragm), and genioglossus motor threshold (MT) and motor-evoked potential (MEP) characteristics. TMS twitches were applied during early inspiration and end expiration at stimulation intensity 30% above LCW/diaphragm and genioglossus MT., Results: Compared with room air, CO(2) inhalation significantly augmented minute ventilation, maximal inspiratory flow, tidal volume, and tidal volume/respiratory time ratio. UA resistance was unchanged with CO(2) inhalation. During 7% CO(2) breathing, LCW/diaphragm MT decreased by 9.6 ± 10.1% whereas genioglossus MT increased by 7.2 ± 9%. CO(2)-induced ventilatory stimulation led to elevation of LCW/diaphragm MEP amplitudes during inspiration but not during expiration. LCW/diaphragm MEP latencies remained unaltered both during inspiration and expiration. Genioglossus MEP latencies and amplitudes were unchanged with CO(2)., Conclusion: In awake, healthy subjects, CO(2)-induced hyperventilation is associated with heightened LCW/diaphragm corticomotor activation without modulating genioglossus MEP responses. This imbalance may promote UA instability during increased respiratory drive.

To assess upper airway (UA) dynamic properties, magnetic stimulation of the phrenic nerves (MSPN) is usually performed at cervical level or anterior-laterally at the neck base. We hypothesized that UA dynamic properties could be effectively assessed by MSPN performed at the sternal level. Instantaneous flow, pharyngeal and mask pressures were recorded in 12 healthy awake subjects. End-expiratory MSPN were applied in random order with a non-focal coil placed behind the 7th cervical vertebrae (C7-MS) and at the sternal level (a-MS). The percentage of flow-limited twitches was greater with a-MS (a-MS: 33% and C7-MS: 2%; P<0.0001). For the non flow-limited twitches, maximal inspiratory flow was 36% greater (P<0.001) and isoflow UA resistance was lower with a-MS (0.6±0.1 and 0.9±0.1 cmH2Ol(-1)s; P=0.02). Maximal inspiratory flow of flow-limited twitches was 78% greater (P=0.05) and isoflow UA resistance tended to be lesser with a-MS (0.9±0.3 and 1.8±0.7 cmH2Ol(-1)s; P=0.09). a-MS could be a practical approach for assessing UA dynamic properties in awake subjects., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: Upper airway collapse does not occur during wake in obstructive sleep apnea patients. This points to wake-related compensatory mechanisms, and possibly to a modified corticomotor control of upper airway dilator muscles. The objectives of the study were to characterize the responsiveness of the genioglossus to transcranial magnetic stimulation during respiratory and non-respiratory facilitatory maneuvers in obstructive sleep apnea patients, and to compare it to the responsiveness of the diaphragm, with reference to normal controls., Methods: Motor evoked potentials of the genioglossus and of the diaphragm, with the corresponding motor thresholds, were recorded in response to transcranial magnetic stimulation applied during expiration, inspiration and during maximal tongue protraction in 13 sleep apnea patients and 8 normal controls., Main Results: In the sleep apnea patients: 1) combined genioglossus and diaphragm responses occurred more frequently than in controls (P < 0.0001); 2) the amplitude of the genioglossus response increased during inspiratory maneuvers (not observed in controls); 3) the latency of the genioglossus response decreased during tongue protraction (not observed in controls). A significant negative correlation was found between the latency of the genioglossus response and the apnea-hypopnea index; 4) the difference in diaphragm and genioglossus cortico-motor responses during tongue protraction and inspiratory loading differed between sleep apnea and controls., Conclusion: Sleep apnea patients and control subjects differ in the response pattern of the genioglossus and of the diaphragm to facilitatory maneuvers, some of the differences being related to the frequency of sleep-related events.

Assessing diaphragm function is clinically and physiologically pertinent. It can rely on the measurement of pressure responses to phrenic stimulation. Combining mouth pressure (Pm) with cervical magnetic stimulation (CMS) is painless and easy to perform, but Pm-CMS poorly reflects esophageal pressure (Pes-CMS) because of poor pressure transmission across the airway. We reasoned that the mouth opening and neck flexion that are associated with the measurement of Pm-CMS would impair upper airway dynamics and further hinder pressure transmission. Therefore, we assessed the CMS-related pressure measured in a nasal mask (Pmask; mouth closed) without neck flexion as a possible surrogate of Pes-CMS, in 14 men and 3 women, age 24.5+/-2.2. Pes-CMS was 15.7+/-4.3 cmH2O, significantly higher than Pm-CMS (13.5+/-5.6 cmH2O, P<0.0001) but not different from Pmask-CMS (15.2+/-4.9 cmH2O). The concordance correlation coefficient was low (0.6808) between Pes-CMS and Pm-CMS. It was higher between Pes-CMS and Pmask-CMS (0.8730). Pm-CMS wrongly classified five subjects as abnormal (<10 cmH2O), versus 1 for Pmask and 5 for Pm (P=0.025). Passing and Bablok regressions found no difference between Pes-CMS and Pmask-CMS, but identified a systematic difference and a proportional error between Pes-CMS and Pm-CMS. We conclude that Pmask-CMS is a better surrogate of Pes-CMS than Pm-CMS.

MB (mouth breathing) promotes the occurrence of sleep-disordered breathing even in non-apnoeic subjects. Considering that MO (mouth opening) contributes to an increase in UA (upper airway) collapsibility independently of MB, the aim of the present study was to assess the influence of breathing route on UA dynamics in the presence of MO. Bilateral anterior magnetic phrenic nerve stimulation was performed 2 s after expiratory onset in 12 healthy male subjects during wakefulness (age, 50+/-5 years; body mass index, 27.8+/-2.4 kg/m(2)) during MB through a mouthpiece and during exclusive NB (nasal breathing) with the same mouthpiece in place. Twitch-induced V(I) (instantaneous flow), P(ph) and P(es) (pharyngeal and oesophageal pressures respectively) were recorded and the corresponding resistances were measured. A polynomial regression model, V(I)=k(1)P(d)+k(2)P(d)(2), was used to characterize flow-pressure relationship and to determine the P(d) value at which UA collapses. There was no difference in UA dynamic properties between NB and MB when UA collapse occurred above the pharyngeal catheter. For twitches where UA collapse occurred lower in the UA, pharyngeal resistance decreased from NB to MB (2.0+/-0.3 and 1.5+/-0.2 cmH(2)Oxl(-1)xs respectively; P=0.02; values are means+/-S.D.), whereas closing pressure increased (-25.7+/-10.1 and -18.0+/-3.0 cmH(2)O respectively; P=0.04). We conclude that (i) in the presence of MO the dynamic properties of the proximal UA free of phasic activity do not differ between NB and MB, and (ii) MB decreases the upstream resistance and increases collapsibility of the distal UA.

Phrenic nerve stimulation (PNS) can assess airflow dynamics of the upper airway (UA) during wakefulness in man. Using PNS, we aimed to assess the impact of neck flexion and mouth opening in promoting UA unstability. Measurements were made during nasal breathing in seven healthy subjects (ages = 23-39 yr; one woman). Surface diaphragm electromyogram, esophageal pressure referenced to mask pressure, and flow were recorded during diaphragm twitches with neck in neutral position and mouth closed and then with neck flexion and/or mouth opening. Twitches always exhibited a flow-limited pattern. Flow-limiting driving pressure (Pd) and peak Pd were increased by neck flexion (P < 0.01) without significant change in the corresponding flows. UA resistances at these flow values were higher with the neck flexed (P < 0.05). Mouth opening alone did not exert any significant influence. We conclude that the position of the neck has a discernible impact on the flow behavior through the nonphasically active UA faced with a negative Pd.

Abstract: Oronasal mask (ONM) can be used when mouth leaks impair nasal-CPAP effectiveness. However, ONM''s constraint on the chin and straps’ traction may alter upper airway (UA) mechanical properties. In contrast, mandibular advancement device associated with nasal-CPAP (NM+MAD) may reduce UA resistance. The aim of this exploratory study was to compare the effects of ONM, NM, and NM+MAD on UA mechanical properties. The three interface modalities were assessed in 11 OSAS patients at 6, 8, 10cmH2O CPAP using a phrenic nerve magnetic stimulation (PNMS) protocol. PNMS-twitches’ related flow, pharyngeal pressures (nasopharynx, velopharynx, oropharynx) and UA resistances were determined. Regardless of CPAP level, twitch-induced maximum flow was higher with NM+MAD than with ONM. Velopharyngeal resistance was higher with ONM than with NM+MAD. Oropharyngeal resistance was higher with ONM than with NM. In conclusion, NM+MAD reduced velopharyngeal resistance compared to those measured with ONM and NM alone. We hypothesize that this strategy may help reducing the effective pressure level and thus further limit the risk for mouth leaks. [Copyright &y& Elsevier]