Exercise-induced Laryngeal Obstruction: Protocol for a Randomized Controlled Treatment Trial.

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, possibly requiring different therapeutic approaches. Currently applied treatments do not rest on randomized controlled trials, and international guidelines based on good evidence can therefore not be established. This study aims to provide evidence-based information on treatment schemes commonly applied in patients with EILO. METHODS AND ANALYSIS: Consenting patients consecutively diagnosed with EILO at Haukeland University Hospital will be randomized into four non-invasive treatment arms, based on 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 inspiratory muscle training and speech therapy. Differential effects in predefined EILO subtypes will be addressed. Patients failing the non-invasive approach and otherwise qualifying for surgical treatment by current department policy will be considered for randomization into (E) standard or (F) minimally invasive laser supraglottoplasty or (G) no surgery. Power calculations are based on the main outcomes, laryngeal adduction during peak exercise, rated by a validated scoring system before and after the interventions. ETHICS AND DISSEMINATION: The study will assess approaches to EILO treatments that despite widespread use, are insufficiently tested in structured, verifiable, randomized, controlled studies, and is therefore considered ethically sound. The study will provide knowledge 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. Dissemination will occur in peer-reviewed journals, at relevant media platforms and conferences, and by engaging with patient organizations and the healthcare bureaucracy.

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.

Pulmonary tularaemia. / Pulmonal tularemi.

BACKGROUND: The diagnosis of pulmonary tularaemia can be challenging. We present a case illustrating how pulmonary tularaemia may be an important radiological differential diagnosis to lung cancer. CASE PRESENTATION: A man in his fifties presented with several weeks of dry cough, weight loss and profuse night sweats. The physical examination was normal. A chest computer tomography showed evidence of lymphadenopathy and two consolidated lung masses. The lung masses and lymph nodes showed signs of necrosis. The radiological findings were described as suspicious of lung cancer. A detailed history revealed that he had chopped wood prior to symptom onset. He tested positive for Francisella tularensis IgM and IgG, confirming the diagnosis of pulmonary tularaemia. INTERPRETATION: The radiological findings in pulmonary tularaemia may mimic lung cancer. Serology is an easy way to confirm the diagnosis, if faced with clinical or radiological suspicion of pulmonary tularaemia.

Exercise Related Respiratory Problems in the Young-Is It Exercise-Induced Bronchoconstriction or Laryngeal Obstruction?

Complaints of breathlessness during heavy exercise is common in children and adolescents, and represent expressions of a subjective feeling that may be difficult to verify and to link with specific diagnoses through objective tests. Exercise-induced asthma and exercise-induced laryngeal obstruction are two common medical causes of breathing difficulities in children and adolescents that can be challenging to distinguish between, based only on the complaints presented by patients. However, by applying a systematic clinical approach that includes rational use of tests, both conditions can usually be diagnosed reliably. In this invited mini-review, we suggest an approach we find feasible in our everyday clinical work.

Severe Exercise-Induced Laryngeal Obstruction Treated With Supraglottoplasty.

Introduction: Exercise induced laryngeal obstruction (EILO) is relatively common in adolescents, with symptoms often confused with exercise induced asthma. EILO often starts with medial or inward rotation of supraglottic structures of the larynx, whereas glottic adduction appears as a secondary phenomenon in a majority. Therefore, surgical treatment (supraglottoplasty) is used in thoroughly selected and highly motivated patients with pronounced symptoms and severe supraglottic collapse. Aim: To investigate efficacy and safety of laser supraglottoplasty as treatment for severe supraglottic EILO by retrospective chart reviews. Methods: The EILO register at Haukeland University Hospital, Bergen, Norway was used to identify patients who had undergone laser supraglottoplasty for severe supraglottic EILO, verified by continuous laryngoscopy exercise (CLE) test, during 2013-2015. Laser incision in both aryepiglottic folds anterior to the cuneiform tubercles and removal of the mucosa around the top was performed in general anesthesia. Outcomes were questionnaire based self-reported symptoms, and laryngeal obstruction scored according to a defined scheme during a CLE-test performed before and after surgery. Results: Forty-five of 65 eligible patients, mean age 15.9 years, were included. Post-operatively, 38/45 (84%) patients reported less symptoms, whereas CLE-test scores had improved in all, of whom 16/45 (36%) had no signs of obstruction. Most improvements were at the supraglottic level, but 21/45 (47%) also improved at the glottic level. Two of 65 patients had complications; self-limiting vocal fold paresis and scarring/shortening of plica ary-epiglottica. Conclusion: Supraglottoplasty improves symptoms and decreases laryngeal obstruction in patients with severe supraglottic EILO, and appears safe in highly selected cases.

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.

Laryngeal Responses to Mechanically Assisted Cough in Progressing Amyotrophic Lateral Sclerosis.

BACKGROUND: Respiratory complications represent the major cause of death in amyotrophic lateral sclerosis (ALS). Noninvasive respiratory support is the mainstay therapy, but treatment becomes challenging as the disease progresses, possibly due to a malfunctioning larynx, which is the entrance to the airways. We studied laryngeal response patterns to mechanically assisted cough (mechanical insufflation-exsufflation) as ALS progresses. METHODS: This prospective longitudinal study of 13 consecutively included subjects with ALS were followed up during 2011-2016 with repeated tests of lung function, neurological status, and laryngeal responses to mechanical insufflation-exsufflation using video-recorded flexible transnasal fiberoptic laryngoscopy. RESULTS: Follow-up time was median 17 (range 6-59) months. In total, 751 laryngoscopy recordings from 67 individual examinations (median 4 per subject, range 2-11 per subject) were analyzed. Adverse laryngeal events that developed with disease progression during insufflation included adduction of true vocal folds in 8 of 9 spinal-onset subjects and adduction of aryepiglottic folds in all subjects, initially at the highest positive pressure and prior to onset of other bulbar symptoms in spinal-onset subjects. As cough became less expulsive with disease progression, laryngeal adduction occurred at lower insufflation pressures. Retroflex movement of the epiglottis was observed in 7 of 13 subjects regardless of insufflation pressures and independent of bulbar involvements. Backward movement of the tongue base occurred regardless of insufflation pressures in all but 1 subject. During exsufflation, constriction of the hypopharynx was observed in all subjects regardless of the presence of bulbar symptoms, after the adverse events that occurred during insufflation. CONCLUSIONS: Applying high insufflation pressures during mechanically assisted cough in ALS can become counterproductive as the disease progresses as well as prior to the onset of bulbar symptoms. The application of positive inspiratory pressures should be tailored to the individual patient, and laryngoscopy during ongoing treatment appears to be a feasible tool.

Laryngeal response patterns influence the efficacy of mechanical assisted cough in amyotrophic lateral sclerosis.

BACKGROUND: Most patients with amyotrophic lateral sclerosis (ALS) are treated with mechanical insufflation-exsufflation (MI-E) in order to improve cough. This method often fails in ALS with bulbar involvement, allegedly due to upper-airway malfunction. We have studied this phenomenon in detail with laryngoscopy to unravel information that could lead to better treatment. METHODS: We conducted a cross-sectional study of 20 patients with ALS and 20 healthy age-matched and sex-matched volunteers. We used video-recorded flexible transnasal fibre-optic laryngoscopy during MI-E undertaken according to a standardised protocol, applying pressures of ±20 to ±50 cm H2O. Laryngeal movements were assessed from video files. ALS type and characteristics of upper and lower motor neuron symptoms were determined. RESULTS: At the supraglottic level, all patients with ALS and bulbar symptoms (n=14) adducted their laryngeal structures during insufflation. At the glottic level, initial abduction followed by subsequent adduction was observed in all patients with ALS during insufflation and exsufflation. Hypopharyngeal constriction during exsufflation was observed in all subjects, most prominently in patients with ALS and bulbar symptoms. Healthy subjects and patients with ALS and no bulbar symptoms (n=6) coordinated their cough well during MI-E. CONCLUSIONS: Laryngoscopy during ongoing MI-E in patients with ALS and bulbar symptoms revealed laryngeal adduction especially during insufflation but also during exsufflation, thereby severely compromising the size of the laryngeal inlet in some patients. Individually customised settings can prevent this and thereby improve and extend the use of non-invasive MI-E.

Laryngeal response patterns to mechanical insufflation-exsufflation in healthy subjects.

OBJECTIVE: Mechanical insufflation-exsufflation (MI-E) is used to assist cough in patients with neuromuscular diseases. Clinically, application may be challenging in some patient groups, possibly related to laryngeal dysfunction. Before launching a study in patients, the authors investigated laryngeal responses to MI-E in healthy individuals. DESIGN: Twenty healthy volunteers, aged 21-29 yrs, were studied with video-recorded flexible transnasal fiber-optic laryngoscopy while performing MI-E using the Cough Assist (Respironics, United States) according to a standardized protocol applying pressures of ±20 to ±50 cm H2O. RESULTS: An initial abduction of the vocal folds was observed in all subjects, both during the insufflation and exsufflation phases. Nineteen of the 20 subjects adequately coordinated glottic closure when instructed to cough. When instructed simply to exhale during exsufflation, the glottis stayed open in a majority. Subsequent to an initial abduction during exsufflation and cough, various obstructive laryngeal movements were observed in some subjects, such as narrowing of the vocal folds, retroflexion of the epiglottis, hypopharyngeal constriction, and backward movement of the base of the tongue. CONCLUSIONS: The larynx can be studied with transnasal laryngoscopy during MI-E in healthy individuals. Laryngeal responses to MI-E vary, and laryngoscopy may offer valuable clinical information when applying MI-E in patients with bulbar muscle weakness.

Laryngeal movements during inspiratory muscle training in healthy subjects.

BACKGROUND: Inspiratory muscle training (IMT) has been used to treat patients with exercise-induced vocal cord dysfunction (VCD); the theoretical basis being the close relationship between the diaphragm and the posterior cricoarytenoid muscle, which is the main abductor of the larynx. Before launching a treatment protocol in patients with VCD, we aimed to substantiate this theory by performing laryngoscopy in healthy subjects during standardized IMT programs. METHODS: Twenty healthy volunteers at mean age 24 years were examined with video-recorded continuous transnasal flexible laryngoscopy while performing standardized training programs using a resistive loading IMT device (Respifit S). All subjects were exposed to two modes of training, that is, the resistance set to generate mouth pressures ≥80% of the maximal attainable inspiratory mouth pressure (PImax) and 60-80% of PImax. Laryngeal movements were scored in retrospect from the video recordings by a senior laryngologist. RESULTS: At pressure settings of ≥80% of PImax, laryngeal movements could not be assessed in one subject. Abduction was observed in 10 (53%) subjects, six to a maximal extent and four to a moderate extent. At pressure settings of 60-80% of PImax, abduction was observed in 18 (90%) subjects, seven to a maximal extent and 11 to a moderate extent. CONCLUSIONS: IMT can produce laryngeal abduction in healthy subjects, and training programs may conceivably contribute positively in patients suffering from laryngeal adduction during exercise. Individual response patterns varied between subjects and individualized programs seem crucial for effect. Use of high resistances seemed to be counterproductive.