Accuracy of the Sensory Test Using the Laryngopharyngeal Endoscopic Esthesiometer in Obstructive Sleep Apnea

Official title

Accuracy of the Sensory Test Performed Using the Laryngopharyngeal Endoscopic Esthesiometer and Rangefinder in Patients With Suspected Obstructive Sleep Apnoea Hypopnea (OSA): a Prospective Double-blinded, Randomised, Pilot Study

Overview

This is a prospective double blinded randomized crossover controlled trial aiming at validating the measurement of laryngopharyngeal mechanosensitivity in patients with suspected OSA using a recently developed laryngopharyngeal endoscopic esthesiometer and rangefinder (LPEER). Subjects will be recruited from patients with suspected OSA referred for baseline polysomnography to a university hospital sleep laboratory. Intra- and inter-rater reliability will be evaluated using the Bland-Altman's limits of agreement plot, the intraclass correlation coefficient, and the Pearson or Spearman correlation coefficient, depending on the distribution of the variables. Diagnostic accuracy will be evaluate plotting Receiver-operating-characteristic-curves (ROC-curves) using as reference standard basal polysomnogram. The sensory threshold values for patients with mild, moderate, and severe OSA, will be determined and compared using ANOVA or Kruskal Wallis test, depending on the distribution of the variables.

Detailed description

INTRODUCTION:

Obstructive sleep apnea-hypopnea syndrome (OSA) patients might have varying degrees of laryngopharyngeal mechanical hyposensitivity; however, these findings come from studies performed with methods having weak inter-rater reliability and accuracy evidence.

The purpose of this study is to validate the measurement of laryngopharyngeal mechanosensitivity in patients with OSA using a recently developed laryngopharyngeal endoscopic esthesiometer and rangefinder (LPEER). The LPEER includes an air-pulse generator and an endoscopic laser rangefinder and works coupled to a conventional fiberoptic endoscope. This device generates air-pulses ranging from 0.04 mN to 16.5 mN in order to cover a wide range of laryngopharyngeal reflexes and sensory thresholds. Depending on the reflex or sensory threshold to be explored the LPEER is configured to deliver a sequence of 10 air-pulses of different intensity.

METHODS:

The study will be prospective, double blinded, and with a randomized and crossover assignment of the raters.

Subjects will be recruited from patients with suspected OSA referred for baseline polysomnography to a sleep laboratory of a tertiary care university hospital. They will undergo a laryngopharyngeal sensory test using the LPEER, which includes measurement of the thresholds for the velopharyngeal, hypopharyngeal and aryepiglottic fold psychophysical sensitivity.

Intra- and inter-rater reliability will be evaluated using the Bland-Altman's limits of agreement plot, the intraclass correlation coefficient, and the Pearson or Spearman correlation coefficient, depending on the distribution of the variables.

Diagnostic accuracy will be evaluate plotting ROC-curves using as reference standard basal polysomnogram. The sensory threshold values for patients with mild, moderate, and severe OSA, will be determined and compared using ANOVA or Kruskal Wallis test, depending on the distribution of the variables.The discriminative capacity as well as correlations between laryngopharyngeal sensory thresholds and OSA severity indexes will be explored in subgroups of subjects with normal and abnormal sensation. The relationship between sensory thresholds and OSA severity indexes will be explored by linear equations as well as by second- and higher-order polynomial equations.

The laryngopharyngeal endoscopic esthesiometer and rangefinder (LPEER), could be a new tool for the evaluation and monitoring of laryngopharyngeal sensory involvement in patients with OSA, which, if proved valid, could help to increase the knowledge about the pathophysiological mechanisms of this condition and potentially help finding new therapeutic interventions for OSA.

ETHICS:

This study will follow the Declaration of Helsinki principles and national legal regulations about research in human subjects. The protocol was approved by the Institutional Review Board of Fundacion Neumologica Colombiana and all recruited subjects will provided a signed informed consent.

DISSEMINATION:

The results will be disseminated through conference presentations and peer-reviewed publication.

Interventions

• Other Laryngopharyngeal sensory test
  The sensory measurements will include thresholds for psychophysical sensory thresholds at the velopharynx, hypopharynx and aryepiglottic folds

Primary outcome measures

• Velopharynx psychophysical sensory threshold [Time frame: 15 days]
• Hypopharynx psychophysical sensory threshold [Time frame: 15 days]
• Aryepiglottic fold psychophysical sensory threshold [Time frame: 15 days]

Secondary outcome measures (4)

• Apnea Hypopnea Index [Time frame: 15 days]
• Oxygen desaturation index [Time frame: 15 days]
• T90 [Time frame: 15 days]
• Adverse Events [Time frame: 15 days]

Eligibility criteria

Inclusion criteria

• Patients being 18 years old or more referred to the sleep laboratory of a tertiary care university hospital for a baseline polysomnography for suspected OSA.

Exclusion criteria

• Anticoagulation (though not a contraindication for the endoscopic laryngopharyngeal sensory test, anticoagulation is an exclusion criteria for this validation study in order to keep it a minimal-risk study).
• Bleeding diathesis.
• Basal awake oxygen saturation by pulse oximetry below 88%.
• Not agree to participate in the study.
• Glasgow coma scale below of 15 (to avoid confusion with involvement of laryngopharyngeal reflexes due to neurological disease accompanied by decreased level of consciousness).
• Baseline polysomnography that does not meet validity criteria to be interpreted (according to the American Academy of Sleep Medicine).
• Baseline polysomnography performed more than 15 days before the sensory testing. Ordinarily, the sensory testing will be performed the same day or the next day of baseline polysomnography.
• More than 5% of total apnoea events being of central origin.
• History of maxillofacial or pharyngeal surgery (to avoid confusion with involvement of laryngopharyngeal reflexes due to surgery in this region).
• Laryngopharyngeal tract malignancies (to avoid confusion with involvement of laryngopharyngeal reflexes due to tumours).
• Central Nervous System (CNS) surgery in the last three months or that has left neurological sequelae (to avoid confusion with involvement of laryngopharyngeal reflexes due to sequelae of CNS surgery).
• Traumatic brain injury in the last three months or more than three month with neurological sequelae.
• History of active neuromuscular disease that affects the muscles of head and neck or with sequels present at the time of the sensory testing (to avoid confusion with involvement of laryngopharyngeal reflexes due to neuromuscular disease).
• History of cerebrovascular disease (to avoid confusion with dysphagia or sensory compromise secondary to cerebrovascular disease).
• Diabetes (to avoid confusion with diabetic neuropathy that compromises the laryngopharyngeal region).
• Chronic use of systemic corticosteroids at a dose greater or equal to 20 mg per day of prednisone or equivalent (to avoid confusion with steroid myopathy that compromises the laryngopharyngeal region).
• Upper respiratory tract infection within 15 days prior to the testing (to avoid confusion with neuropathy associated with respiratory viral disease that compromises the laryngopharyngeal region).
• Patient's inability to cooperate during the examination (to avoid measurement error caused by the lack of cooperation of the patient).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Crossover

Masking

Quadruple blind

Primary purpose

Diagnostic

Study locations

Colombia · 2 centers

• Fundacion Neumologica Colombiana — Bogotá
• Universidad de la Sabana — Chía

Publications

• Miyaji H, Hironaga N, Umezaki T, Hagiwara K, Shigeto H, Sawatsubashi M, Tobimatsu S, Komune S. Neuromagnetic detection of the laryngeal area: Sensory-evoked fields to air-puff stimulation. Neuroimage. 2014 Mar;88:162-9. doi: 10.1016/j.neuroimage.2013.11.008. Epub 2013 Nov 15. PMID 24246493
• Nguyen AT, Jobin V, Payne R, Beauregard J, Naor N, Kimoff RJ. Laryngeal and velopharyngeal sensory impairment in obstructive sleep apnea. Sleep. 2005 May;28(5):585-93. doi: 10.1093/sleep/28.5.585. PMID 16171271
• Aviv JE, Martin JH, Sacco RL, Zagar D, Diamond B, Keen MS, Blitzer A. Supraglottic and pharyngeal sensory abnormalities in stroke patients with dysphagia. Ann Otol Rhinol Laryngol. 1996 Feb;105(2):92-7. doi: 10.1177/000348949610500202. PMID 8659942
• Aviv JE, Sacco RL, Mohr JP, Thompson JL, Levin B, Sunshine S, Thomson J, Close LG. Laryngopharyngeal sensory testing with modified barium swallow as predictors of aspiration pneumonia after stroke. Laryngoscope. 1997 Sep;107(9):1254-60. doi: 10.1097/00005537-199709000-00018. PMID 9292613
• Jordan AS, McSharry DG, Malhotra A. Adult obstructive sleep apnoea. Lancet. 2014 Feb 22;383(9918):736-47. doi: 10.1016/S0140-6736(13)60734-5. Epub 2013 Aug 2. PMID 23910433
• Teramoto S, Sudo E, Matsuse T, Ohga E, Ishii T, Ouchi Y, Fukuchi Y. Impaired swallowing reflex in patients with obstructive sleep apnea syndrome. Chest. 1999 Jul;116(1):17-21. doi: 10.1378/chest.116.1.17. PMID 10424498
• Valbuza JS, de Oliveira MM, Zancanella E, Conti CF, Prado LB, Carvalho LB, do Prado GF. Swallowing dysfunction related to obstructive sleep apnea: a nasal fibroscopy pilot study. Sleep Breath. 2011 May;15(2):209-13. doi: 10.1007/s11325-010-0474-9. Epub 2011 Jan 13. PMID 21229321
• Giraldo-Cadavid LF, Burguete J, Rueda F, Galvis AM, Castaneda N, Agudelo-Otalora LM, Moscoso WD, Paez N, Fernandez S. Reliability of a laryngo-pharyngeal esthesiometer and a method for measuring laryngo-pharyngeal mechano-sensitivity in a prospectively recruited cohort of patients. Eur Arch Otorhinolaryngol. 2017 Jul;274(7):2861-2870. doi: 10.1007/s00405-017-4536-5. Epub 2017 Mar 24. PMID 28341965

Identifiers

NCT: NCT03109171 · 201611-22405

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗