Assessing laryngeal function and hypersensitivity.

The larynx is one of the most highly innervated organs in humans, adapted to simultaneously deliver several key respiratory functions including airway protection, swallowing and phonation. In some individuals the larynx can adopt a state that could be considered 'dysfunctional' or maladaptive; resulting in or contributing to a range of clinical disorders such as chronic refractory cough, inducible laryngeal obstruction (previously termed paradoxical vocal fold movement or vocal cord dysfunction), muscle tension dysphonia and globus pharyngeus. These disorders appear to display significant overlap in clinical symptomology and in many cases have features of concomitant or allied sensory dysfunction; often described as laryngeal hypersensitivity. The recognition and accurate assessment of both laryngeal dysfunction±hypersensitivity is important to ensure accurate diagnosis and effective delivery of targeted treatment and therapeutic monitoring. Accordingly, there is increasing in the methodologies proposed to assess laryngeal function. These range from simple questionnaires to targeted investigation(s), assessing both sensory function and the laryngeal motor response, under both resting and provoked situations. This review provides a brief overview of the current state of knowledge in the field of laryngeal dysfunction and hypersensitivity assessment.

Cough in exercise and athletes.

Cough is the most common respiratory symptom reported by athletes and can significantly impact on health status, ability to train and athletic performance. The presence of cough in an athlete is typically taken to indicate exercise-induced bronchoconstriction (EIB), yet in many athletes with chronic cough there is no objective evidence of airway hyper-responsiveness (AHR) or heightened airway inflammation. Moreover, cough in athletes often fails to respond to a therapeutic asthma strategy, thus further work is urgently needed to progress our understanding of the pathophysiology of exercise-associated cough in this unique population. This article provides an overview of the current state of knowledge of exercise-associated cough in athletes. The article summarises our understanding of pathophysiological basis of cough in this context and provides a pragmatic clinical approach to this problem.

Lesson of the month: Rowing-induced laryngeal obstruction: a novel cause of exertional dyspnoea: characterised by direct laryngoscopy.

Exercise-induced laryngeal obstruction (EILO) is a key differential diagnosis for unexplained dyspnoea in athletes. The gold standard means for diagnosis of EILO is direct laryngoscopy, performed continuously, while an athlete undertakes the specific sport that precipitates their symptoms. This report provides the first descriptions of rowing-associated EILO in two competitive rowers presenting with unexplained dyspnoea and cough. The report describes the methodology and safety of the use of continuous laryngoscopy in the context of maximal rowing ergometry and the use of this technique as a therapeutic tool to provide biofeedback.

Dynamic laryngeal narrowing during exercise: a mechanism for generating intrinsic PEEP in COPD?

INTRODUCTION: Patients with COPD commonly exhibit pursed-lip breathing during exercise, a strategy that, by increasing intrinsic positive end-expiratory pressure, may optimise lung mechanics and exercise tolerance. A similar role for laryngeal narrowing in modulating exercise airways resistance and the respiratory cycle volume-time course is postulated, yet remains unstudied in COPD. The aim of this study was to assess the characteristics of laryngeal narrowing and its role in exercise intolerance and dynamic hyperinflation in COPD. METHODS: We studied 19 patients (n=8 mild-moderate; n=11 severe COPD) and healthy age and sex matched controls (n=11). Baseline physiological characteristics and clinical status were assessed prior to an incremental maximal cardiopulmonary exercise test with continuous laryngoscopy. Laryngeal narrowing measures were calculated at the glottic and supra-glottic aperture at rest and peak exercise. RESULTS: At rest, expiratory laryngeal narrowing was pronounced at the glottic level in patients and related to FEV1 in the whole cohort (r=-0.71, p<0.001) and patients alone (r=-0.53, p=0.018). During exercise, glottic narrowing was inversely related to peak ventilation in all subjects (r=-0.55, p=0.0015) and patients (r=-0.71, p<0.001) and peak exercise tidal volume (r=-0.58, p=0.0062 and r=-0.55, p=0.0076, respectively). Exercise glottic narrowing was also inversely related to peak oxygen uptake (% predicted) in all subjects (r=-0.65, p<0.001) and patients considered alone (r=-0.58, p=0.014). Exercise inspiratory duty cycle was related to exercise glottic narrowing for all subjects (r=-0.69, p<0.001) and patients (r=-0.62, p<0.001). CONCLUSIONS: Dynamic laryngeal narrowing during expiration is prevalent in patients with COPD and is related to disease severity, respiratory duty cycle and exercise capacity.

Pathophysiological mechanisms of exercise-induced anaphylaxis: an EAACI position statement.

This document is the result of a consensus on the mechanisms of exercise-induced anaphylaxis (EIAn), an unpredictable and potentially fatal syndrome. A multidisciplinary panel of experts including exercise physiologists, allergists, lung physicians, paediatricians and a biostatistician reached the given consensus. Exercise-induced anaphylaxis (EIAn) describes a rare and potentially fatal syndrome in which anaphylaxis occurs in conjunction with exercise. The pathophysiological mechanisms underlying EIAn have not yet been elucidated although a number of hypotheses have been proposed. This review evaluates the validity of each of the popular theories in relation to exercise physiology and immunology. On the basis of this evidence, it is concluded that proposed mechanisms lack validity, and it is recommended that a global research network is developed with a common approach to the diagnosis and treatment of EIAn in order to gain sufficient power for scientific evaluation.

Laryngeal hypersensitivity in chronic cough.

Patients with chronic cough often report symptoms arising in the throat, in response to non-specific stimuli. Accordingly, the concept of a 'hypersensitivity' of the larynx in chronic cough has evolved over the past ten years. Patients with cough and laryngeal hypersensitivity frequently report features that overlap other laryngeal dysfunction syndromes, including a tendency for the vocal cords to inappropriately adduct. The mechanisms underlying laryngeal hypersensitivity in chronic cough are currently unclear, however recent studies provide new clinical and physiological techniques to aid detection and monitoring of laryngeal hypersensitivity. This review provides an overview of the current state of knowledge in this field.

Airway dysfunction in elite athletes--an occupational lung disease?

Airway dysfunction is prevalent in elite endurance athletes and when left untreated may impact upon both health and performance. There is now concern that the intensity of hyperpnoea necessitated by exercise at an elite level may be detrimental for an athlete's respiratory health. This article addresses the evidence of causality in this context with the aim of specifically addressing whether airway dysfunction in elite athletes should be classified as an occupational lung disease. The approach used highlights a number of concerns and facilitates recommendations to ensure airway health is maintained and optimized in this population. We conclude that elite athletes should receive the same considerations for their airway health as others with potential and relevant occupational exposures.

Recovery from COVID-19 in athletes and impact on sporting participation.

Insight regarding the impact of COVID-19 on return to sporting participation is a key issue for many athletes. We report time-loss following respiratory tract infection (RTI), over the pandemic, in UK athletes preparing for international competition. During the study, 566 athletes developed COVID-19 and 217 developed other causes of RTI. Time-loss from COVID-19 reduced from a median (interquartile range) of 27 days (13- 40) in April-June 2020 to 10 days (8-13) from October-December 2022 (P<0.001). There was no change in time-loss following RTi (P=0.13). The time-loss period following COVID-19 has shortened over the pandemic. Further work is needed to explore why some athletes still have prolonged sporting time-loss.

Misdiagnosis of exercise-induced bronchoconstriction in professional soccer players.

BACKGROUND: Physicians typically rely heavily on self-reported symptoms to make a diagnosis of exercise-induced bronchoconstriction (EIB). However, in elite sport, respiratory symptoms have poor diagnostic value. In 2009, following a change in international sports regulations, all elite athletes suspected of asthma and/or EIB were required to undergo pulmonary function testing (PFT) to permit the use of inhaled ß(2)-agonists. The aim of this study was to examine the diagnostic accuracy of physician diagnosis of asthma/EIB in English professional soccer players. METHODS: Sixty-five players with a physician diagnosis of asthma/EIB were referred for pulmonary function assessment. Medication usage and respiratory symptoms were recorded by questionnaire. A bronchial provocation test with dry air was conducted in 42 players and a mannitol challenge in 18 players. Five players with abnormal resting spirometry performed a bronchodilator test. RESULTS: Of the 65 players assessed, 57 (88%) indicated regular use of asthma medication. Respiratory symptoms during exercise were reported by 57 (88%) players. Only 33 (51%) of the players tested had a positive bronchodilator or bronchial provocation test. Neither symptoms nor the use of inhaled corticosteroids were predictive of pulmonary function tests' outcome. CONCLUSION: A high proportion of English professional soccer players medicated for asthma/EIB (a third with reliever therapy only) do not present reversible airway obstruction or airway hyperresponsiveness to indirect stimuli. This underlines the importance of objective PFT to support a symptoms-based diagnosis of asthma/EIB in athletes.

The impact of a heat and moisture exchange mask on respiratory symptoms and airway response to exercise in asthma.

Respiratory symptoms, including cough, are prevalent in individuals with asthma when exercising. This study investigates whether a heat and moisture exchanger (HME) face mask is effective in modulating exercise-induced bronchoconstriction (EIB) and post-exercise cough in a cold, dry environment in individuals with asthma. Twenty-six participants diagnosed with asthma (20 males, 6 females) completed three cycling exercise challenges at 8°C and 24% relative humidity in a randomised order. Participants wore either an HME mask (MASK), sham mask (SHAM), or no mask (CONT). Following a 3-min warm-up, participants completed 6-min cycling at 80% peak power output. Before and after exercise, maximal flow-volume loops were recorded. Post-exercise cough was monitored with a Leicester Cough Monitor (LCM) for 24 h. Results were analysed using repeated-measures ANOVA and Friedman's tests and data were presented as the mean±sd or median (interquartile range (IQR)). Eleven participants failed to demonstrate EIB (i.e. >10% fall in forced expiratory volume in 1 s after exercise) and were removed from analysis. The percentage fall in forced expiratory volume in 1 s following exercise in CONT was greater than MASK (MASK: -6% (7%), SHAM: -11% (11%), CONT: -13% (9%); p<0.01). No difference was found between exercise in cough count per hour over the 24-h monitoring period or the number of coughs in the first hour after exercise. HME masks can attenuate EIB when exercising in cold, dry environments. The SHAM mask may not have been entirely inert, demonstrating the challenges of running randomised control trials utilising control and sham conditions.

Increased augmentation index in patients with cystic fibrosis.

Increased large artery stiffness occurs in a range of inflammatory conditions indicating an ageing of the vasculature and additionally being an independent risk factor for cardiovascular events. We determined large artery parameters in adults with cystic fibrosis (CF). 50 clinically stable adult patients with CF (mean+/-sd age 28.0+/-8.2 yrs) and 26 controls matched for age, sex and body mass index were studied. Central aortic blood pressure, augmentation index (AIx) and aortic pulse wave velocity (PWV) were determined using applanation tonometry. Lung function, diabetic status and C-reactive protein (CRP) were also determined. Mean+/-sd AIx was greater in patients than controls, 8.5+/-11.1% and -1.8+/-13.1%, respectively (p<0.001), while PWV was similar. Although AIx was greatest in the sub-group with CF-related diabetes (CFRD), it was also increased in the non-CFRD sub-group when compared with controls. In patients, AIx was related to log(10) CRP (r = 0.33) and forced vital capacity (r = -0.34; both p<0.05), and CRP remained predictive in multiple regression. AIx is increased in adults with CF, in the presence of a normal blood pressure and independent of diabetic status. AIx was related to the systemic inflammatory status. These findings have implications for management and require further exploration so that cardiovascular health can be maintained.

A novel approach to central venous catheter thrombosis in a patient with cystic fibrosis.

Catheter directed thrombolysis has been described as a treatment for large pulmonary emboli resistant to systemic therapy [Kelly P, Carroll N, Grant C, Barrett C, Kocka V. Successful treatment of massive pulmonary embolism with prolonged catheter-directed thrombolysis. Heart Vessels 2006;21:124?6]. We now describe a case in which local catheter directed thrombolysis, via a peripherally inserted central catheter (PICC), was used to treat a large thrombus surrounding the tip of an indwelling central venous line that was causing superior vena cava obstruction (SVCO), in a patient with cystic fibrosis.

Effect of metoclopramide on digoxin absorption from tablets and capsules.

The effect of metoclopramide, a drug that increases gut motility, on the consistency of digoxin absorption was examined in 16 healthy men. Each received the following four single-dose digoxin treatments in complete crossover fashion: two 0.25-mg digoxin tablets, alone, and two 0.2-mg digoxin capsules with metoclopramide. Mean serum AUCs over 24 hr (AUC-24) and cumulative urinary digoxin excretion over 48 hr (CUE-48) were of the same order for the tablets and capsules alone treatments. Metoclopramide reduced the mean AUC-24 for tablets from 12.26 +/- 2.70 to 9.38 +/- 3.78 ng X hr/ml (P less than 0.001) and the CUE-48 from 119.0 +/- 22.4 to 97.6 +/- 22.2 micrograms (P less than 0.01). There were no significant differences in mean AUC-24 (12.94 +/- 3.16 and 13.45 +/- 2.33 ng X hr/ml) and mean CUE-48 (117.8 +/- 23.4 and 109.7 +/- 25.0 micrograms) when capsules alone were compared to capsules with metoclopramide. Metoclopramide reduced the time to reach peak concentration for both digoxin dosage forms. The effect of metoclopramide on digoxin absorption is minimized by administration of digoxin in capsules.

Digital plethysmography for assessing erythrityl tetranitrate bioavailability.

The bioavailability or oral, sublingual, and chewable tablets or erythrityl tetranitrate (ETN) was evaluated in 15 normal men. In a randomized, complete crossover investigation with nitroglycerin and placebo controls, drug-induced changes in the diastolic amplitude response intensity were measured with a digital plethysmogram. Values for area under the response intensity curve (AUC), maximum response intensity (Imax), and time lapse from dosing to peak response (tmax) were obtained by computer processing and converted to intensity values and AUC segments for specific time intervals. Sublingual nitroglycerin induced a response (p less than 0.05) from placebo within the first hour. Although somewhat slower in reaching peak intensity, all forms of ETN induced significant responses over placebo (p less than 0.05) for 2 hr, with oral (swallowed) ETN different 6 hr. Our results indicate that all the ETN dosage forms were bioavailable, with the longest duration of effect by the oral form.

Potential anticoagulant drug interactions in ambulatory patients.

Computer-generated prescription drug purchase records for ambulatory patients receiving oral anticoagulants (OAC) were studied for concomitant use of other drugs which have been reported to induce clinically significant interactions. One third of 479 patients taking OAC were exposed to a potentially interacting drug at some time during this 6-month period. The percentage of patients with drug interaction exposure correlated directly with total drug use (p less than 0.0005). There were no significant differences when interaction exposure rates were compared in the cases of single : multiple pharmacy and single : multiple physician-patient groups. Warfarin was the most common anticoagulant (greater than 95%) and barbiturates the most common interacting drug.

Influence of range of renal function and liver disease on predictability of creatinine clearance.

Several formulas for predicting creatinine clearance (Ccr) are used for adjusting drug dosages but limited data are available on their accuracy in patients with significant renal impairment or concurrent disease. We measured 144 Ccr in 103 patients and compared results using four predictive methods. Of nine common diseases in these patients, liver disease was associated with a large (p less than 0.02) prediction error (overprediction). After data from eight patients with liver disease were removed, there was good overall correlation between predicted and measured Ccr (r2 = 0.91 for each method) but only two of the methods (I and IV) were consistently accurate in all ranges of renal function. Methods for predicting Ccr should not be used in patients with liver disease.

Codeine disposition in smokers and nonsmokers.

The bioavailability of codeine and extent of its transformation to morphine were stated in 12 smoking and 11 nonsmoking subjects after single doses 60 mg IM codeine and 60 mg codeine sulfate orally, given 1 wk apart. Codeine and morphine plasma concentrations over the 12-hr period after drug were determined by radioimmunoassay (RIA). No differences were found between smokers and nonsmokers with respect to maximum plasma concentration (Cmax) of codeine, time to attain this concentration (tmax), codeine plasma half-life (t1/2), or areas under plasma concentration-time curves (AUC) for codeine or morphine. There was a faster, but clinically unimportant, mean apparent plasma clearance in smokers (52.8 +/- 2.3 (SEM) ml/min/70 kg) than in nonsmokers (45.0 +/- 2.1 ml/min/70 kg) after intramuscular injection only. Mean oral codeine bioavailability in smokers (54.8 +/- 4.9%) and in nonsmokers (50.2 +/- 2.1%) did not offer. Plasma morphine AUC values were higher after oral doses than after intramuscular injections, suggesting a first-pass O-demethylation of codeine. For six of these subjects plasma morphine AUC values were very low after both routes of administration, suggesting less O-demethylation of codeine in these than in the remaining 17 subjects. The observation of higher morphine AUC values after oral codeine, coupled with clinical reports of greater analgesic potency with intramuscular codeine, does not support the hypothesis that the analgesic properties of this drug are mediated entirely by biotransformation to morphine.