HelpILO - RCT on EILO Treatment

Official title

Exercise Induced Laryngeal Obstruction; a Randomized Controlled Treatment Trial

Overview

Exercise induced laryngeal obstruction (EILO) is a common cause of exertional breathing problems in young individuals, caused by paradoxical inspiratory adduction of laryngeal structures, and diagnosed by continuous visualization of the larynx during high intensity exercise.

Detailed description

Exercise induced laryngeal obstruction (EILO) is a common cause of exertional breathing problems in young individuals, caused by paradoxical inspiratory adduction of laryngeal structures, and diagnosed by continuous visualization of the larynx during high intensity exercise.

Studies indicate that EILO responds positively to treatment interventions; however, the investigators lack randomized controlled studies to confirm this (10-15). This study aims to provide evidence-based information on interventions commonly applied to treat EILO. Background: Exercise induced laryngeal obstruction (EILO) is a common cause of exertional breathing problems in young individuals, caused by paradoxical inspiratory adduction of laryngeal structures, and diagnosed by continuous visualization of the larynx during high intensity exercise. Empirical data suggest that EILO consists of different subtypes that require different therapeutic approaches. However, currently applied treatment schemes do not rest on randomized controlled trials. This study aims to provide evidence-based information on treatment schemes commonly applied in patients with EILO.

Methods: Consenting patients consecutively diagnosed with EILO at Haukeland University Hospital will be randomized into four different conservative treatment arms, selected on the basis of promising reports from non-randomized studies: (A) standardized information and breathing advice only (IBA), (B) IBA plus inspiratory muscle training, (C) IBA plus speech therapy, and (D) IBA plus provision of both inspiratory muscle training and speech therapy. Differential effects in predefined EILO subtypes will be addressed. Patients failing the conservative approach and otherwise qualifying for surgical treatment by current department policy will be considered for randomization into (E) standard or (F) minimal laser supraglottoplasty, and a "wait-and-see" control group. Power calculations will be based on the main outcomes, laryngeal adduction during peak exercise, rated by a validated scoring system before and after the interventions.

Discussion: The study will provide evidence-based information on the treatment of EILO, listed as a priority in a recent statement issued by the European Respiratory Society, requested by clinicians and researchers engaged in this area, and relevant to 5-7% of young people.

Interventions

• Procedure A: Breathing advice with bio-feedback
  Information and breathing advice with biofeedback will serve as an active comparator in this study, and time allowed for IBA and biofeedback in this study will be max 30 min. The teaching will be provided by the attending physician and the test leader. The session will follow a strict checklist. After the laryngoscope has been secured in correct position the patient will be shown his/her larynx on the screen, providing the patient with basic knowledge on laryngeal anatomy and function in a calm
• Procedure B: Breathing advice with bio-feedback, Inspiratory muscle training (IMT)
  Breathing advise and IMT. The inspiratory muscle training (IMT) will build on the information the patients have obtained during the IBA and biofeedback session. The IMT will focus on training endurance and coordination of the PCA muscle, aiming to reduce fatigue of the abducting capacity of the larynx and to enhance coordination and create a sense of laryngeal control. When performing the IMT sessions, it is of utmost importance that a functional diaphragmatic breathing pattern has been establis
• Procedure C: Breathing advice with bio-feedback, Speech Therapy
  The training period with the speech therapist takes three days, divided into 6 sessions. The training is continued at home, implementing the techniques during physical activity and at rest. The aim of the speech therapy is to help the patients to develop a strategy on how to control his/her larynx during exercise, and to be able to continue exercising without experiencing dramatic EILO incidents. They will be informed that the best approach is to start practicing while performing low to moderate
• Procedure D: Breathing advice with bio-feedback, IMT and Speech Therapy
  All treatments as described above.
• Procedure A: If CLE-test unchanged, additional IMT and Speech Therapy
  All treatments as described above.
• Procedure Surgery 1: Supraglottoplasty - full procedure under general anesthesia
  Endoscopic supraglottoplasty with carbon dioxide laser and cold steel microlaryngeal instruments. The patient is intubated with an armored laser-tube which is positioned in the posterior midline to protect this area from laser injury. The laryngoscope is positioned into the vallecula and the surgery is visualized through an operation-microscope. CO2-laser beams of 2-4W focused with micro spot is utilized. Releasing incisions are made at the anterior border of both AEFs. The depth of the incision
• Procedure Surgery 2: Supraglottoplasty - mini-invasive procedure under general anesthesia
  Endoscopic supraglottoplasty with carbon dioxide laser. The patients are intubated with an armored laser-tube, which is positioned in the posterior midline to protect this area from laser injury. The laryngoscope (Benjamin/Lindholm) is positioned into the vallecula and the surgery is visualized through an operation-microscope. CO2-laser beams of 2-4W focused with micro spot are utilized. Four punctures will be made along the lateral borders of both aryepiglottic folds bilateral, thus creating a

Primary outcome measures

• Questionnaires [Time frame: Day 1]
• Pulmonary function and exercise test - Spirometry 1 [Time frame: Through study completion, on average 6 months]
• Pulmonary function and exercise test - Spirometry 2 [Time frame: Through study completion, on average 6 months]
• Pulmonary function and exercise test - Spirometry 3 [Time frame: Through study completion, on average 6 months]
• Continuous Laryngoscopy Exercise test (CLE-test) and scoring [Time frame: Through study completion, on average 6 months]
• Cardiopulmonary exercise (CPX) data - Variables of gas exchange [Time frame: Through study completion, on average 6 months]
• Cardiopulmonary exercise (CPX) data - duration of run [Time frame: Through study completion, on average 6 months]
• Cardiopulmonary exercise (CPX) data - distance of run [Time frame: Through study completion, on average 6 months]
• Cardiopulmonary exercise (CPX) data - oxygen consumption [Time frame: Through study completion, on average 6 months]
• Cardiopulmonary exercise (CPX) data - CO2 production [Time frame: Through study completion, on average 6 months]

Eligibility criteria

Inclusion criteria

• EILO with CLE score at peak exercise graded as ≥ 2 at glottic or supraglottic level and
• Respiratory complaints to an extent that the patient wants further treatment and follow-up.

Exclusion criteria

• Breathing problems caused by disorders other than EILO or well controlled asthma.
• Perceived to be unable to perform repeated maximal cardiopulmonary treadmill exercise tests, or failing to accept the procedures required for repeated successful CLE tests, or unable to perform any of the other examinations required by the protocol.
• Abnormal anatomy at rest in the laryngeal region or the upper airways.
• Age below 12 years

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

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Factorial

Masking

Double blind

Primary purpose

Treatment

Study locations

Norway · 1 center

• Haukeland University Hospital, Children and Youth Clinic — Bergen

Publications

• Halvorsen T, Clemm HSH, Vollsaeter M, Roksund OD. Conundrums of Exercise-related Breathing Problems. Epiglottic, Laryngeal, or Bronchial Obstruction? Am J Respir Crit Care Med. 2020 Nov 15;202(10):e142-e143. doi: 10.1164/rccm.201910-1921IM. No abstract available. PMID 32783778
• Engan M, Engeseth MS, Fevang S, Vollsaeter M, Eide GE, Roksund OD, Halvorsen T, Clemm H. Predicting physical activity in a national cohort of children born extremely preterm. Early Hum Dev. 2020 Jun;145:105037. doi: 10.1016/j.earlhumdev.2020.105037. Epub 2020 Apr 11. PMID 32438296
• Fretheim-Kelly ZL, Halvorsen T, Clemm H, Roksund O, Heimdal JH, Vollsaeter M, Fintl C, Strand E. Exercise Induced Laryngeal Obstruction in Humans and Equines. A Comparative Review. Front Physiol. 2019 Oct 30;10:1333. doi: 10.3389/fphys.2019.01333. eCollection 2019. PMID 31736771
• Sandnes A, Hilland M, Vollsaeter M, Andersen T, Engesaeter IO, Sandvik L, Heimdal JH, Halvorsen T, Eide GE, Roksund OD, Clemm HH. Severe Exercise-Induced Laryngeal Obstruction Treated With Supraglottoplasty. Front Surg. 2019 Jul 31;6:44. doi: 10.3389/fsurg.2019.00044. eCollection 2019. PMID 31417908
• Sandnes A, Andersen T, Clemm HH, Hilland M, Vollsaeter M, Heimdal JH, Eide GE, Halvorsen T, Roksund OD. Exercise-induced laryngeal obstruction in athletes treated with inspiratory muscle training. BMJ Open Sport Exerc Med. 2019 Jan 18;5(1):e000436. doi: 10.1136/bmjsem-2018-000436. eCollection 2019. PMID 30792880
• Fretheim-Kelly Z, Halvorsen T, Heimdal JH, Strand E, Vollsaeter M, Clemm H, Roksund O. Feasibility and tolerability of measuring translaryngeal pressure during exercise. Laryngoscope. 2019 Dec;129(12):2748-2753. doi: 10.1002/lary.27846. Epub 2019 Jan 30. PMID 30698834
• Andersen TM, Sandnes A, Fondenes O, Clemm H, Halvorsen T, Nilsen RM, Tysnes OB, Heimdal JH, Vollsaeter M, Roksund OD. Laryngoscopy Can Be a Valuable Tool for Unexpected Therapeutic Response in Noninvasive Respiratory Interventions. Respir Care. 2018 Nov;63(11):1459-1461. doi: 10.4187/respcare.06674. No abstract available. PMID 30389835
• Clemm HSH, Sandnes A, Vollsaeter M, Hilland M, Heimdal JH, Roksund OD, Halvorsen T. The Heterogeneity of Exercise-induced Laryngeal Obstruction. Am J Respir Crit Care Med. 2018 Apr 15;197(8):1068-1069. doi: 10.1164/rccm.201708-1646IM. No abstract available. PMID 29390192

Identifiers

NCT: NCT04620343 · 2020/134444

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗