Emil Schwarz Walsted

Bronchial provocation testing does not detect exercise-induced laryngeal obstruction

ABSTRACT Introduction: Exercise-induced laryngeal obstruction (EILO) is a key differential diagnosis for asthma in the presence of exertional respiratory symptoms. Continuous laryngoscopy during exercise (CLE), the current gold standard diagnostic test for EILO, has practical limitations. We aimed to establish if inspiratory flow data obtained during standard bronchoprovocation testing, to establish the presence of extra-thoracic hyper-responsiveness, may prove diagnostic for EILO and thus preclude requirement for CLE testing. Methods: We consecutively evaluated 37 adult subjects with exertional dyspnea and possible asthma referred over 6 months. All subjects received comprehensive assessment including a detailed clinical evaluation; pulmonary function testing, indirect and direct bronchial provocation testing, and CLE testing. Results: Out of 37 subjects, moderate or severe EILO was diagnosed in 8 subjects (22%, all female) while 5 (14%) had both asthma and EILO. There was no correlation between degree of EILO during CLE and mean decrease in forced inspiratory flow (%FIF50) obtained during neither the Methacholine (r = −0.15; p = 0.38) nor Mannitol (r = 0.04; p = 0.84) provocation tests. Conclusion: Inspiratory flow parameters obtained during bronchoprovocation tests did not reliably detect EILO. It remains that CLE is an important and key investigation modality in establishing a secure diagnosis of EILO.

Inducible laryngeal obstruction: an official joint European Respiratory Society and European Laryngological Society statement.

Inducible laryngeal obstruction (ILO) describes an inappropriate, transient, reversible narrowing of the larynx in response to external triggers. ILO is an important cause of a variety of respiratory symptoms and can mimic asthma. Current understanding of ILO has been hampered by imprecise nomenclature and variable approaches to assessment and management. A task force of the European Respiratory Society (ERS) and European Laryngological Society (ELS) was thus set up to address this, and to identify research priorities. A literature search identified relevant articles published until June 2016, using all identifiable terms for ILO, although including only articles using laryngoscopy. In total, 172 out of 252 articles met the inclusion criteria, summarised in sections on diagnostic approach, aetiology, comorbidities, epidemiology and treatment. The consensus taxonomy published by ERS, ELS and the American College of Chest Physicians (ACCP) in 2015 is used throughout this statement. We highlight the high prevalence of ILO and the clinical impact for those affected. Despite recent advances, most aspects of this condition unfortunately remain incompletely understood, precluding firm guidance. Specifically, validated diagnostic and treatment algorithms are yet to be established, and no randomised control studies were identified in this search; hence we also make recommendations for future research. The larynx in respiratory medicine: an updated official statement from the ERS and ELS http://ow.ly/2WQ130dqLPp

Laryngoscopy during swimming: A novel diagnostic technique to characterize swimming- induced laryngeal obstruction

Exercise‐induced laryngeal obstruction (EILO) is a key differential diagnosis for respiratory symptoms in athletes and is particularly prevalent in aquatic athletes. A definitive diagnosis of EILO is dependent on laryngoscopy, performed continuously, while an athlete engages in the sport that precipitates their symptoms. This report provides the first description of the feasibility of performing continuous laryngoscopy during exercise in a swimming environment. The report describes the methodology and safety of the use of continuous laryngoscopy while swimming. Laryngoscope, 127:2298–2301, 2017

Novel assessment tool to detect breathing pattern disorder in patients with refractory asthma

Breathing pattern disorder (BPD) can co‐exist with and mimic asthma, acting to amplify symptoms and confound assessment of disease control, resulting in inappropriate treatment escalation. The aim of this research was to report the utility of a novel breathing pattern assessment tool (BPAT) to detect BPD in treatment‐refractory asthma.

Validity and reliability of grade scoring in the diagnosis of exercise-induced laryngeal obstruction

The current gold-standard method for diagnosing exercise-induced laryngeal obstruction (EILO) is continuous laryngoscopy during exercise (CLE), with severity classified by a visual grade scoring system. We evaluated the precision of this approach, by evaluating test–retest reliability of CLE and both inter- and intra-rater variability. In this prospective case–control study, subjects completed four consecutive treadmill CLE tests under identical conditions. Laryngoscopic video recordings were anonymised and graded by three expert raters. 2 months following initial scoring, videos were re-randomised and rating repeated to assess intra-rater agreement. 20 subjects (16 cases and four controls) completed four CLE tests. The time to exhaustion increased by 30 s (95% CI 0.02–57.8, p<0.05) in the second CLE compared with the first test, but remained identical in the subsequent tests. Only one-third of subjects retained their initial diagnosis in the subsequent three tests. Inter-rater agreement on grade scores (weighted Cohens ϰ) was 0.16–0.45, while intra-rater agreement ranged from 0.30 to 0.67. The CLE test is key in the diagnostic assessment of patients with EILO. However, the widely adopted visual grade scoring system does not appear to be a robust means for reliably classifying severity of EILO. Validity and reliability of grade scoring in exercise-induced laryngeal obstruction (EILO) http://ow.ly/cDWV30cClFX

Exercise-Induced Laryngeal Obstruction—An Overview

Exertional dyspnea is common in health and disease. Despite having known for centuries that breathlessness can arise from the larynx, exercise-induced laryngeal obstruction is a more prevalent condition than previously assumed. This article provides a brief overview of the history, epidemiology, and pathophysiology of exercise-induced laryngeal obstruction.

Heredity of supraglottic exercise-induced laryngeal obstruction

Respiratory symptoms on exertion, such as shortness of breath and wheezing, are commonly associated with asthma, but might also arise from the larynx [1–3]. In recent years, the emergence of exercise laryngoscopy [4] has led to a better understanding of laryngeal movement during exercise, and inspiratory supraglottic collapse on exertion has been established as a common cause of exertional breathlessness [5] that is correlated with exercise intensity [6]. Both glottic and supraglottic inspiratory closure are more commonly seen in females and most often in adolescents or young adults [7–11]. This predominance has yet to be explained; however, gender differences in larynx size/growth and consequently higher “Bernoulli forces” in females for a given respiratory demand could be a contributing factor [5]. Thus, an inherited disorder affecting laryngeal growth could also explain why the condition usually presents in adolescence [12, 13]. A recent study by Hilland and colleagues [14] describing an association between congenital laryngomalacia and (mainly supraglottic) laryngeal closure in adolescence, points out a likely predisposition for supraglottic exercise-induced laryngeal obstruction (EILO), whereas case studies have demonstrated that congenital laryngomalacia can be inherited [15, 16]. Supraglottic EILO could be inherited. Different modes of inheritance can explain the results of this study. http://ow.ly/5XAv30csDRa

Increased respiratory neural drive and work of breathing in exercise-induced laryngeal obstruction

Exercise-induced laryngeal obstruction (EILO), a phenomenon in which the larynx closes inappropriately during physical activity, is a prevalent cause of exertional dyspnea in young individuals. The physiological ventilatory impact of EILO and its relationship to dyspnea are poorly understood. The objective of this study was to evaluate exercise-related changes in laryngeal aperture on ventilation, pulmonary mechanics, and respiratory neural drive. We prospectively evaluated 12 subjects (6 with EILO and 6 healthy age- and gender-matched controls). Subjects underwent baseline spirometry and a symptom-limited incremental exercise test with simultaneous and synchronized recording of endoscopic video and gastric, esophageal, and transdiaphragmatic pressures, diaphragm electromyography, and respiratory airflow. The EILO and control groups had similar peak work rates and minute ventilation (V̇e) (work rate: 227 ± 35 vs. 237 ± 35 W; V̇e: 103 ± 20 vs. 98 ± 23 l/min; P > 0.05). At submaximal work rates (140-240 W), subjects with EILO demonstrated increased work of breathing ( P < 0.05) and respiratory neural drive ( P < 0.05), developing in close temporal association with onset of endoscopic evidence of laryngeal closure ( P < 0.05). Unexpectedly, a ventilatory increase ( P < 0.05), driven by augmented tidal volume ( P < 0.05), was seen in subjects with EILO before the onset of laryngeal closure; there were however no differences in dyspnea intensity between groups. Using simultaneous measurements of respiratory mechanics and diaphragm electromyography with endoscopic video, we demonstrate, for the first time, increased work of breathing and respiratory neural drive in association with the development of EILO. Future detailed investigations are now needed to understand the role of upper airway closure in causing exertional dyspnea and exercise limitation. NEW & NOTEWORTHY Exercise-induced laryngeal obstruction is a prevalent cause of exertional dyspnea in young individuals; yet, how laryngeal closure affects breathing is unknown. In this study we synchronized endoscopic video with respiratory physiological measurements, thus providing the first detailed commensurate assessment of respiratory mechanics and neural drive in relation to laryngeal closure. Laryngeal closure was associated with increased work of breathing and respiratory neural drive preceded by an augmented tidal volume and a rise in minute ventilation.

The asthma-plus syndrome

In the vast majority of cases, asthma can be successfully treated and controlled with regular inhaled therapy. In a proportion of individuals (i.e. approximately 5% of the asthma population), however, their disease appears to be refractory to standard therapy and can be described as ‘difficult-to-treat’ [1,2]. Individuals with ‘difficult’ or ‘refractory’ asthma often continue to suffer frequent exacerbations and persistent dyspnea, despite up-escalation in therapy [2]. In the context of severe asthma, it is certainly promising to see the recent development and subsequent licensing of several novel treatments [3]. Indeed, within the past year, a number of biologic agents (e.g. Mepolizumab and Reslizumab) have become available, targeting a Type-2 inflammatory pattern [3–5]. These therapies certainly considerably advance the available treatment options in severe asthma and indeed for many individuals will be transformational. However, despite this progress, it will remain the case that for some with ‘difficult’ asthma these treatments will not be indicated or only of limited benefit. Why is this? The cornerstone of evaluating any individual with ‘difficult-totreat’ or refractory asthma is to gain a rich understating of their clinical condition utilizing a systematic assessment process [6]. The latter, now endorsed in several international guidelines [1,7,8], employs a multidisciplinary approach (e.g. including physiotherapy, nurse specialist, and psychology input) to holistically appraise any individual labeled as having ‘severe asthma.’ The process acts to ensure the primary diagnosis (i.e. asthma) is robust, to characterize phenotypic features, but also to assess and treat important yet often overlooked contributory factors, for example, poor adherence, optimal delivery of inhaled therapy, and coexisting pulmonary diagnoses [9]. Accordingly, a systematic assessment for refractory asthma is now considered the gold standard approach and is cost-effective [10] and improves asthma-related quality of life [11,12]. A key component in the systematic assessment process is evaluating the contribution from additional respiratory factors causing dyspnea and ‘airway-centric’ respiratory symptoms, for example, wheeze and cough. In this respect, our knowledge has advanced significantly over the past 5 years with improved recognition of the contribution from two key areas causing respiratory system dysfunction: first, from abnormal or maladaptive breathing patterns (also termed dysfunctional breathing (DB)), and second, from inappropriate, episodic closure of the larynx. Historically, respiratory physicians have viewed these entities as acting to ‘mimic’ asthma, and it undoubtedly remains true that closure of the larynx and/or breathing pattern disorders may cause significant respiratory symptoms, in the absence of asthma [13,14]. Yet, there is now evolving appreciation that these conditions can actually coexist with severe asthma and may thus, in many cases, be better viewed as components of an ‘asthma-plus’ syndrome. The larynx appears to play a key role in regulating lung emptying [15] and is known to modulate pulmonary function in response to bronchoconstriction [16] and exercise [13]. Indeed while a minor degree of closure of the larynx during expiration is considered normal, paradoxical closure during inspiration is atypical and maladaptive. This phenomenon, in the presence of respiratory symptoms, is most often termed vocal cord dysfunction (VCD) and has been recognized to mimic asthma for over 30 years [17]. It is, however, only more recently that this entity, now termed inducible-laryngeal obstruction (ILO) [18], has been shown to coexist and potentially amplify the symptoms of severe asthma. In this respect, Low et al. [19] reported that approximately half of a cohort of 50 patients with difficult-to-treat asthma had abnormal laryngeal closure. In a further larger study, utilizing CT diagnostics, the same group [20] found a similarly high prevalence of abnormal vocal cord closure, with heightened inspiratory phase closure found in 42 of 155 (27%) asthmatics. Increased age and airflow obstruction were associated with the presence of abnormal vocal cord closure. Likewise, Tay et al. [21] recently reported that approximately one-third of a cohort of patients evaluated in a difficult asthma service had VCD. The high prevalence of DB in asthma has been recognized for many years. Specifically, Thomas et al. [22] reported a prevalence of DB of approximately 30% in a questionnaire survey of 219 patients with community diagnosed asthma, with prevalence independent of disease severity (i.e. by treatment step of treatment). More recently, Veidal et al. [23] reported a prevalence of DB of 24% in those with objectively confirmed asthma (i.e. using bronchodilator or bronchoprovocation testing) and found an independent influence of DB on asthma control, even when adjusted for lung function, airway hyperreactivity, demographics, and medication use. That is,

Time-course of changes to intrathoracic pressure induced by CPAP in normal subjects

Introduction: An understanding of the changes in intra-thoracic pressure in response to application of CPAP (Continuous Positive Airway Pressure) is important in the study of airway and ventilator mechanics. It is unclear how quickly intrathoracic pressure measured directly with balloon catheters responds to change in CPAP. We have studied the time course of stabilisation of pressures in normal subjects.. Methods: Mouth pressure (Pmo) was measured directly at the facemask with a NIPPY 3 CPAP; oesophageal (Poes) and gastric(Pga) pressures were measured with balloon catheters in 5 normal subjects, aged 32-65, seated at rest, with 10 minutes no CPAP, then 20 minutes at CPAP 5cmH 2 O, then 10cm H 2 O and then 10 minutes no CPAP. Results: Mouth pressure (Pmo) at the facemask was lower than prescribed CPAP; CPAP 5cmH 2 O=Pmo 4.3cm H 2 O;CPAP 10cmH 2 O=8.14cmH 2 O. Change in prescribed CPAP pressure was followed by change in Pmo and Poes within 60 seconds for all pressure changes, but the corresponding change in Pga was more variable; up to 470 seconds to stabilise. Conclusions: Mouth pressure with CPAP is less than prescribed through leakage. Gastric pressure change in response to change in CPAP takes longer and varies more than for Pmo and Poes. This may reflect variation in diaphragm tonicity as noted before (Am J Respir Crit Care Med 1999;160:513-22).It may have methodological implications for studying the impact of pressure change with CPAP.