Prevalence and impact of exercise-induced laryngeal obstruction in asthma: a study protocol for a cross-sectional and longitudinal study.

INTRODUCTION: Exercise-induced laryngeal obstruction (EILO) and exercise-induced asthma can cause troublesome respiratory symptoms that can be difficult to distinguish between. Further, there is now a growing appreciation that the two conditions may coexist, complicating the interpretation of symptoms. The primary aim of this study is to investigate the prevalence of EILO in patients with asthma. Secondary aims include evaluation of EILO treatment effects and investigation of comorbid conditions other than EILO in patients with asthma. METHODS AND ANALYSIS: The study will be conducted at Haukeland University Hospital and Voss Hospital in Western Norway, and enrol 80-120 patients with asthma and a control group of 40 patients without asthma. Recruitment started in November 2020, and data sampling will continue until March 2024. Laryngeal function will be assessed at baseline and at a 1-year follow-up, using continuous laryngoscopy during high-intensity exercise (CLE). Immediately after the EILO diagnosis is verified, patients will be treated with standardised breathing advice guided by visual biofeedback from the laryngoscope video screen. The primary outcome will be the prevalence of EILO in patients with asthma and control participants. Secondary outcomes include changes in CLE scores, asthma-related quality of life, asthma control and number of the asthma exacerbations, as assessed between baseline and the 1-year follow-up. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Regional Committee for Medical and Health Research Ethics, Western Norway, (ID number 97615). All participants will provide signed informed consent before enrolment. The results will be presented in international journals and conferences. TRIAL REGISTRATION NUMBER: NCT04593394.

Diagnosis of vocal cord dysfunction/inducible laryngeal obstruction: An International Delphi Consensus Study.

BACKGROUND: Vocal cord dysfunction/inducible laryngeal obstruction (VCD/ILO) is characterized by breathing difficulties in association with excessive supraglottic or glottic laryngeal narrowing. The condition is common and can occur independently; however, it may also be comorbid with other disorders or mimic them. Presentations span multiple specialties and misdiagnosis or delayed diagnosis is commonplace. Group-consensus methods can efficiently generate internationally accepted diagnostic criteria and descriptions to increase clinical recognition, enhance clinical service availability, and catalyze research. OBJECTIVES: We sought to establish consensus-based diagnostic criteria and methods for VCD/ILO. METHODS: We performed a modified 2-round Delphi study between December 7, 2021, and March 14, 2022. The study was registered at ANZCTR (Australian New Zealand Clinical Trials Registry; ACTRN12621001520820p). In round 1, experts provided open-ended statements that were categorized, deduplicated, and amended for clarity. These were presented to experts for agreement ranking in round 2, with consensus defined as ≥70% agreement. RESULTS: Both rounds were completed by 47 international experts. In round 1, 1102 qualitative responses were received. Of the 200 statements presented to experts across 2 rounds, 130 (65%) reached consensus. Results were discussed at 2 international subject-specific conferences in June 2022. Experts agreed on a diagnostic definition for VCD/ILO and endorsed the concept of VCD/ILO phenotypes and clinical descriptions. The panel agreed that laryngoscopy with provocation is the gold standard for diagnosis and that ≥50% laryngeal closure on inspiration or Maat grade ≥2 define abnormal laryngeal closure indicative of VCD/ILO. CONCLUSIONS: This Delphi study reached consensus on multiple aspects of VCD/ILO diagnosis and can inform clinical practice and facilitate research.

Associations between biological maturity level, match locomotion, and physical capacities in youth male soccer players.

INTRODUCTION: Biological maturity level has shown to affect sport performance in youths. However, most previous studies have used noninvasive methods to estimate maturity level. Thus, the main aim of the present study was to investigate the association between skeletal age (SA) as a measure of biological maturation level, match locomotion, and physical capacity in male youth soccer players. METHOD: Thirty-eight Norwegian players were followed during two consecutive seasons (U14 and U15). Match locomotion was assessed with GPS-tracking in matches. SA, assessed by x-ray, physical capacities (speed, strength and endurance) and anthropometrics were measured in the middle of each season. Analysis of associations between SA, match locomotion, and physical capacities were adjusted for the potential confounding effect of body height and weight. RESULTS: In matches, positive associations were found between SA and maximal speed and running distance in the highest speed zones. Further, SA was associated with 40 m sprint time and countermovement jump (CMJ) height, and with intermittent-endurance capacity after adjusting for body height (U14). Associations between SA and leg strength and power, and between SA and absolute VO2max were not significant after adjusting for body weight. There was no association between SA and total distance covered in matches. CONCLUSION: Biological maturity level influence match locomotion and performance on physical capacity tests. It is important that players, parents and coaches are aware of the advantages more mature players have during puberty, and that less mature players also are given attention, appropriate training and match competition to ensure proper development.

International Olympic Committee (IOC) consensus statement on acute respiratory illness in athletes part 1: acute respiratory infections.

Acute illnesses affecting the respiratory tract are common and form a significant component of the work of Sport and Exercise Medicine (SEM) clinicians. Acute respiratory illness (ARill) can broadly be classified as non-infective ARill and acute respiratory infections (ARinf). The aim of this consensus is to provide the SEM clinician with an overview and practical clinical approach to ARinf in athletes. The International Olympic Committee (IOC) Medical and Scientific Commission appointed an international consensus group to review ARill (non-infective ARill and ARinf) in athletes. Six subgroups of the IOC Consensus group were initially established to review the following key areas of ARill in athletes: (1) epidemiology/risk factors for ARill, (2) ARinf, (3) non-infective ARill including ARill due to environmental exposure, (4) acute asthma and related conditions, (5) effects of ARill on exercise/sports performance, medical complications/return-to-sport and (6) acute nasal/vocal cord dysfunction presenting as ARill. Several systematic and narrative reviews were conducted by IOC consensus subgroups, and these then formed the basis of sections in the consensus documents. Drafting and internal review of sections were allocated to 'core' members of the consensus group, and an advanced draft of the consensus document was discussed during a meeting of the main consensus core group in Lausanne, Switzerland on 11 to 12 October 2021. Final edits were completed after the meeting. This consensus document (part 1) focusses on ARinf, which accounts for the majority of ARill in athletes. The first section of this consensus proposes a set of definitions and classifications of ARinf in athletes to standardise future data collection and reporting. The remainder of the consensus paper examines a wide range of clinical considerations related to ARinf in athletes: epidemiology, risk factors, pathology/pathophysiology, clinical presentation and diagnosis, management, prevention, medical considerations, risks of infection during exercise, effects of infection on exercise/sports performance and return-to-sport guidelines.

International Olympic Committee (IOC) consensus statement on acute respiratory illness in athletes part 2: non-infective acute respiratory illness.

Acute respiratory illness (ARill) is common and threatens the health of athletes. ARill in athletes forms a significant component of the work of Sport and Exercise Medicine (SEM) clinicians. The aim of this consensus is to provide the SEM clinician with an overview and practical clinical approach to non-infective ARill in athletes. The International Olympic Committee (IOC) Medical and Scientific Committee appointed an international consensus group to review ARill in athletes. Key areas of ARill in athletes were originally identified and six subgroups of the IOC Consensus group established to review the following aspects: (1) epidemiology/risk factors for ARill, (2) infective ARill, (3) non-infective ARill, (4) acute asthma/exercise-induced bronchoconstriction and related conditions, (5) effects of ARill on exercise/sports performance, medical complications/return-to-sport (RTS) and (6) acute nasal/laryngeal obstruction presenting as ARill. Following several reviews conducted by subgroups, the sections of the consensus documents were allocated to 'core' members for drafting and internal review. An advanced draft of the consensus document was discussed during a meeting of the main consensus core group, and final edits were completed prior to submission of the manuscript. This document (part 2) of this consensus focuses on respiratory conditions causing non-infective ARill in athletes. These include non-inflammatory obstructive nasal, laryngeal, tracheal or bronchial conditions or non-infective inflammatory conditions of the respiratory epithelium that affect the upper and/or lower airways, frequently as a continuum. The following aspects of more common as well as lesser-known non-infective ARill in athletes are reviewed: epidemiology, risk factors, pathology/pathophysiology, clinical presentation and diagnosis, management, prevention, medical considerations and risks of illness during exercise, effects of illness on exercise/sports performance and RTS guidelines.

Adjustments of non-invasive ventilation and mechanically assisted cough by combining ultrasound imaging of the larynx with transnasal fibre-optic laryngoscopy: a protocol for an experimental study.

INTRODUCTION: Application of non-invasive positive airway pressure may provoke laryngeal responses that obstruct the airways, especially in patients with disturbed laryngeal control. To control and adjust for this, transnasal fibre-optic laryngoscopy (TFL) is used to visualise laryngeal movements during therapeutic interventions. Being an invasive procedure, this may be unpleasant for patients. The aim of this study is to evaluate if ultrasound (US) imaging of the larynx may be used as an alternative less invasive diagnostic tool for evaluating the upper airway responses to non-invasive ventilation (NIV) and mechanical insufflation-exsufflation (MI-E). METHODS AND ANALYSIS: This protocol presents an experimental cross-sectional study of a novel method to study laryngeal responses in adult healthy volunteers (n=30). The participants will be assessed with simultaneous TFL and laryngeal US imaging (anterior and lateral approaches) during NIV and MI-E therapy. Additionally, airflow and pressure signals will be registered during the procedures. The primary outcome is whether laryngeal US is a feasible method to study laryngeal responses and, if so, to compare the laryngeal responses visualised with TFL and US. The participants' perception of the examinations will be recorded. Secondary outcomes include airflow curve shapes and calculated ventilation volumes during the interventions. ETHICS AND DISSEMINATION: The study has been approved by The Regional Committee for Medical Research Ethics in Norway, and registered in ClinicalTrials.gov. Results will be disseminated through peer-reviewed journals, presentation of scientific abstracts at international medical conventions and oral presentations in relevant medical conventions. TRIAL REGISTRATION NUMBER: NCT04586855.

Tracking of lung function from 10 to 35 years after being born extremely preterm or with extremely low birth weight.

BACKGROUND: Lifelong pulmonary consequences of being born extremely preterm or with extremely low birth weight remain unknown. We aimed to describe lung function trajectories from 10 to 35 years of age for individuals born extremely preterm, and address potential cohort effects over a period that encompassed major changes in perinatal care. METHODS: We performed repeated spirometry in three population-based cohorts born at gestational age ≤28 weeks or with birth weight ≤1000 g during 1982-85, 1991-92 and 1999-2000, referred to as extremely preterm-born, and in term-born controls matched for age and gender. Examinations were performed at 10, 18, 25 and 35 years. Longitudinal data were analysed using mixed models regression, with the extremely preterm-born stratified by bronchopulmonary dysplasia (BPD). RESULTS: We recruited 148/174 (85%) eligible extremely preterm-born and 138 term-born. Compared with term-born, the extremely preterm-born had lower z-scores for forced expiratory volume in 1 s (FEV1) at most assessments, the main exceptions were in the groups without BPD in the two youngest cohorts. FEV1 trajectories were largely parallel for the extremely preterm- and term-born, also during the period 25-35 years that includes the onset of the age-related decline in lung function. Extremely preterm-born had lower peak lung function than term-born, but z-FEV1 values improved for each consecutive decade of birth (p=0.009). More extremely preterm-than term-born fulfilled the spirometry criteria for chronic obstructive pulmonary disease, 44/148 (30%) vs 7/138 (5%), p<0.001. CONCLUSIONS: Lung function after extremely preterm birth tracked in parallel, but significantly below the trajectories of term-born from 10 to 35 years, including the incipient age-related decline from 25 to 35 years. The deficits versus term-born decreased with each decade of birth from 1980 to 2000.

Conundrums in the breathless athlete; exercise-induced laryngeal obstruction or asthma?

PURPOSE: Exercise-induced bronchoconstriction (EIB) and exercise-induced laryngeal obstruction (EILO) are the two disorders commonly considered when athletes complain of exertional dyspnea. They are highly different but often confused. We aimed to address this diagnostic challenge and its consequences in elite athletes. METHODS: We included all athletes competing at national or international level, referred to our institution for workup for EILO during 2013-2016. We diagnosed EILO from video-recorded laryngoscopy performed during maximal cardiopulmonary treadmill exercise (CLE test). Symptoms and previous diagnostic evaluations were obtained from referral letters and chart reviews. RESULTS: Exercise-induced laryngeal obstruction was diagnosed in 73/101 referred athletes, of whom 70/73 had moderate/severe supraglottic obstruction and 3/73 had primarily glottic obstruction with only minor supraglottic involvement. Of the 73 athletes with EILO, we were able to identify objective tests for asthma in 55 participants, of whom 22 had findings supporting asthma. However, 58/73 had used asthma therapy at some time previously, with current use in 28. Only three reported that asthma medication had improved their exercise-related breathing problems, two of whom with tests confirming asthma. Treatment for EILO improved breathing problems in all but four. CONCLUSIONS: Objective testing verified EILO in most of the referred athletes. EILO coexisting with asthma was common, and large proportions had used asthma medication; however, few reported effect on exercise-related breathing problems. Unexplained persistent exertional dyspnea must not lead to indiscriminate escalation of asthma treatment, but instead incite investigation for EILO, either as a co-morbidity or as a differential diagnosis.

Exercise-induced laryngeal obstruction (EILO) in athletes: a narrative review by a subgroup of the IOC Consensus on 'acute respiratory illness in the athlete'.

Exercise-induced laryngeal obstruction (EILO) is caused by paradoxical inspiratory adduction of laryngeal structures during exercise. EILO is an important cause of upper airway dysfunction in young individuals and athletes, can impair exercise performance and mimic lower airway dysfunction, such as asthma and/or exercise-induced bronchoconstriction. Over the past two decades, there has been considerable progress in the recognition and assessment of EILO in sports medicine. EILO is a highly prevalent cause of unexplained dyspnoea and wheeze in athletes. The preferred diagnostic approach is continuous visualisation of the larynx (via laryngoscopy) during high-intensity exercise. Recent data suggest that EILO consists of different subtypes, possibly caused via different mechanisms. Several therapeutic interventions for EILO are now in widespread use, but to date, no randomised clinical trials have been performed to assess their efficacy or inform robust management strategies. The aim of this review is to provide a state-of-the-art overview of EILO and guidance for clinicians evaluating and treating suspected cases of EILO in athletes. Specifically, this review examines the pathophysiology of EILO, outlines a diagnostic approach and presents current therapeutic algorithms. The key unmet needs and future priorities for research in this area are also covered.

Clinical responses following inspiratory muscle training in exercise-induced laryngeal obstruction.

PURPOSE: Exercise-induced laryngeal obstruction (EILO) is relatively common in young people. Treatment rests on poor evidence; however, inspiratory muscle training (IMT) has been proposed a promising strategy. We aimed to assess laryngeal outcomes shortly after IMT, and to compare self-reported symptoms with a control group 4-6 years later. METHODS: Two groups were retrospectively identified from the EILO-register at Haukeland University Hospital, Norway; one group had received only information and breathing advice (IBA), and another additionally IMT (IBA + IMT). At diagnosis, all participants performed continuous laryngoscopy during exercise (CLE), with findings split by glottic and supraglottic scores, and completed a questionnaire mapping exercise-related symptoms. After 2-4 weeks, the IBA + IMT-group was re-evaluated with CLE-test. After 4-6 years, both groups were re-assessed with a questionnaire. RESULTS: We identified 116 eligible patients from the EILO-register. Response rates after 4-6 years were 23/58 (40%) and 32/58 (55%) in the IBA and IBA + IMT-group, respectively. At diagnosis, both groups rated symptoms similarly, but laryngeal scores were higher in the IBA + IMT-group (P = 0.003). After 2-4 weeks, 23/32 in the IBA + IMT-group reported symptom improvements, associated with a decrease of mainly glottic scores (1.7-0.3; P < 0.001), contrasting unchanged scores in the 9/32 without symptom improvements. After 4-6 years, exercise-related symptoms and activity levels had decreased to similar levels in both groups, with no added benefit from IMT; however, full symptom resolution was reported by only 8/55 participants. CONCLUSION: Self-reported EILO symptoms had improved after 4-6 years, irrespective of initial treatment. Full symptom resolution was rare, suggesting individual follow-up should be offered.

Changes in pulmonary function and feasibility of portable continuous laryngoscopy during maximal uphill running.

OBJECTIVE: To evaluate changes in pulmonary function and feasibility of portable continuous laryngoscopy during maximal uphill running. METHODS: Healthy volunteers participated in an uphill race. Forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were obtained before and 5 and 10 min after finishing the race. Capillary blood lactate concentration ([BLa-]) and Borg score for perceived exertion were registered immediately after the race. One participant wore a portable video-laryngoscope during the race, and the video was assessed for technical performance. RESULTS: Twenty adult subjects participated with a mean (SD) age of 40.2 (9.7) years. Mean (SD) race duration and post-exercise [BLa-] was 13.9 (2.3) min and 10.7 (2.1) mmol/L, respectively, and the median (range) Borg score for perceived exertion was 9 (5-10). Mean percentage change (95% CI) 5 and 10 min post-exercise in FEV1 were 6.9 (3.7 to 10.2) % and 5.9 (2.7 to 9.0) %, respectively, and in FVC 5.2 (2.3 to 8.1) % and 4.7 (1.6 to 7.9) %, respectively. The recorded video of the larynx was of good quality. CONCLUSIONS: Maximal aerobic field exercise induced bronchodilatation in the majority of the healthy non-asthmatic participants. It is feasible to perform continuous video-laryngoscopy during heavy uphill exercise.

Exercise-induced laryngeal obstruction in athletes treated with inspiratory muscle training.

BACKGROUND: Exercise-induced laryngeal obstruction (EILO) is common in athletes and presents with dyspnoea, chest tightness, inspiratory stridor and sometimes panic reactions. The evidence for conservative treatment is weak, but case reports suggest effects from inspiratory muscle training (IMT). We aimed to explore effects from IMT used in athletes with EILO. METHOD: Twenty-eight athletes, mean age 16.4 years, diagnosed with EILO at our clinic, participated in a 6-week treatment programme, using a resistive flow-dependent IMT device (Respifit S). Four athletes competed at international level, 13 at national and 11 at regional levels. Video-recorded continuous transnasal flexible laryngoscopy was performed from rest to peak exercise (continuous laryngoscopy exercise (CLE) test) and scored before and 2-4 weeks after the training period. Ergospirometric variables were obtained from this CLE set-up. Lung function was measured according to guidelines. Symptom scores and demographic variables were obtained from a questionnaire. RESULTS: After the treatment period, symptoms had decreased in 22/28 (79%) participants. Mean overall CLE score had improved after treatment (p<0.001), with the scores becoming normal in five athletes but worse in two. Most of the improvement was explained by changes at the glottic laryngeal level (p=0.009). Ergospirometric variables revealed significantly higher peak minute ventilation explained by higher tidal volumes and were otherwise unchanged. CONCLUSION: This explorative study underlines the heterogeneous treatment response of EILO and suggests that IMT may become an efficient conservative treatment tool in subgroups, possibly contributing to better control of the vocal folds. The signals from this study should be tested in future controlled interventional studies.