Diagnostic work-up of exercise-induced laryngeal obstruction.

PURPOSE: Exercise-induced laryngeal obstruction (EILO) is suspected when dyspnea associated with upper airway symptoms is triggered by exercise. This condition affects mainly adolescent athletes. Visualization of the obstruction, while the patient is experiencing the symptoms during continuous laryngoscopy during exercise (CLE-test) is the gold standard for diagnosing EILO. Our study aims to evaluate the prevalence of EILO in a population presenting exercise-induced inspiratory symptoms (EIIS) or uncontrolled asthma with exertional symptoms. The second objective was to evaluate the diagnostic strength of laryngology consultation (LC) and pulmonary function tests (PFTs). METHODS: All patients referred to our center for EIIS or uncontrolled asthma with exertional symptoms were included. EILO diagnosis was made if Maat score was > 2 for patients with CLE-test or if there were inspiratory anomalies on PFTs and LC. The sensitivity and specificity of LC and PFTs as diagnostic tools were calculated considering CLE-test as the gold standard. RESULTS: Sixty two patients were referred to our center for EIIS or uncontrolled asthma with exertional symptoms. EILO was diagnosed in 28 patients (56%) with associated asthma in 9 patients (18%). The sensibility and specificity of LC for supraglottic anomalies were 75% and 60%, respectively. The sensibility and specificity of PFTs were 61% and 89%, respectively. CONCLUSIONS: There was a high prevalence of EILO among patients with EIIS and uncontrolled asthma. Some clinical characteristics might guide the diagnosis. Nevertheless, CLE-test remained the gold standard for EILO diagnosis and identification of the dysfunctional upper airway site to provide specific management.

Sleep-disordered breathing and ventilatory chemosensitivity in first ischaemic stroke patients: a prospective cohort study.

RATIONALE: Sleep-disordered breathing (SDB) is highly prevalent after stroke. The clinical and ventilatory chemosensitivity characteristics of SDB, namely obstructive, central and coexisting obstructive and central sleep apnoea (coexisting sleep apnoea) following stroke are poorly described. OBJECTIVE: To determine the respective clinical and ventilatory chemosensitivity characteristics of SDB at least 3 months after a first ischaemic stroke. METHODS: Cross-sectional analysis of a prospective, monocentric cohort conducted in a university hospital. 380 consecutive stroke or transient ischaemic attack patients were screened between December 2016 and December 2019. MEASUREMENTS AND MAIN RESULTS: Full-night polysomnography, and hypercapnic ventilatory response were performed at a median (Q1; Q3) time from stroke onset of 134.5 (97.0; 227.3) days. 185 first-time stroke patients were included in the analysis. 94 (50.8%) patients presented no or mild SDB (Apnoea-Hypopnoea Index <15 events/hour of sleep) and 91 (49.2%) moderate to severe SDB, of which 52 (57.1%) presented obstructive sleep apnoea and 39 (42.9%) coexisting or central sleep apnoea. Obstructive sleep apnoea patients significantly differed regarding their clinical presentation from patients with no or mild SDB, whereas there was no difference with coexisting and central sleep apnoea patients. The latter presented a higher frequency of cerebellar lesions along with a heightened hypercapnic ventilatory response compared with no or mild SDB patients. CONCLUSION: SDB in first-time stroke patients differ in their presentation by their respective clinical traits and ventilatory chemosensitivity characteristics. The heightened hypercapnic ventilatory response in coexisting and central sleep apnoea stroke patients may orientate them to specific ventilatory support.

Prevalence and Factors Contributing to Daytime and Nocturnal Hypoxemia in Chronic Heart Failure Patients.

BACKGROUND: Despite clinical optimization, many chronic heart failure (CHF) patients remain symptomatic with dyspnea and poor quality of life. STUDY OBJECTIVE: While oxygen therapy is prescribed in severe cases, the actual prevalence of different patterns of hypoxemia is unknown. METHODS: We analyzed 183 stable CHF patients with optimized medical treatment in the "MARS" database. The patients underwent cardiorespiratory sleep recording and complete daytime pulmonary function tests including arterial blood gases. RESULTS: This prospective cohort was predominately male (86.3%) with a mean age of 67.3 years (59.3; 75.7) and a mean BMI of 26.7 kg/m2 (23.7; 31.1). The patients were mainly in NYHA classes II and III with a mean left ventricular ejection fraction of 38%. 102 (55.61%) patients had ischemic cardiomyopathy with multiple comorbidities, and 64 (35.06%) had airflow obstruction. 8 (4.37%) patients had hypoxemia both day and night, and 151 (82.5%) had nocturnal hypoxemia only. All but 3 patients had sleep-disordered breathing (SDB), and either obstructive (59%) or central sleep apnea (39%) with a mean apnea-hypopnea index of 29.59/h (16.48; 48.27), an oxygen desaturation index of 27.09/h (14.09; 45.25), time below 90% saturation of 18 min (2; 64), and a mean nocturnal saturation of 93% (92; 94). Univariate analysis found nocturnal hypoxemia was associated with higher BMI and NT-proBNP levels. In multivariate analysis, only sleep apnea severity (p < 0.0001) and diurnal PaO2 remained significant. CONCLUSION: Most stable CHF patients suffer from nocturnal hypoxemia, while daytime hypoxemia is relatively rare. The degree of nocturnal hypoxemia depends on the severity of SDB. Hypoxemia phenotyping and severity could help better evaluate the need for appropriate therapy in CHF patients.

Contribution of obstructive sleep apnoea to arterial stiffness: a meta-analysis using individual patient data.

BACKGROUND: Arterial stiffness, measured by pulse wave velocity (PWV), is a strong independent predictor of late cardiovascular events and mortality. It is recognised that obstructive sleep apnoea (OSA) is associated with cardiovascular comorbidities and mortality. Although previous meta-analyses concluded that PWV is elevated in OSA, we feel that an individual patient data analysis from nine relatively homogeneous studies could help answer: to what extent does OSA drive arterial stiffness? METHODS: Individual data from well-characterised patients referred for suspicion of OSA, included in nine studies in which carotid-femoral PWV was measured using a Complior device, were merged for an individual patient data meta-analysis. RESULTS: 893 subjects were included (age: 56±11 (mean±SD), 72% men, 84% with confirmed OSA). Body Mass Index varied from 15 to 81 kg/m2 (30±7 kg/m2). PWV ranged from 5.3 to 20.5 m/s (10.4±2.3 m/s). In univariate analysis, log(PWV) was strongly related to age, gender, systolic blood pressure, presence of type 2 diabetes (all p<0.01) as well as to dyslipidaemia (p=0.03) and an Epworth Sleepiness Scale score ≥9 (p=0.04), whereas it was not related to obesity (p=0.54), a severe Apnoea-Hypopnoea Index (p=0.14), mean nocturnal saturation (p=0.33) or sleep time with oxygen saturation below 90% (p=0.47). In multivariable analysis, PWV was independently associated with age, systolic blood pressure and diabetes (all p<0.01), whereas severe OSA was not significantly associated with PWV. CONCLUSION: Our individual patient meta-analysis showed that elevated arterial stiffness in patients with OSA is driven by conventional cardiovascular risk factors rather than apnoea parameters.

Computed Tomography Registration-Derived Regional Ventilation Indices Compared to Global Lung Function Parameters in Patients With COPD.

CT registration-derived indices provide data on regional lung functional changes in COPD. However, because unlike spirometry which involves dynamic maximal breathing maneuvers, CT-based functional parameters are assessed between two static breath-holds, it is not clear how regional and global lung function parameters relate to each other. We assessed the relationship between CT-density change (dHU), specific volume change (dsV), and regional lung tissue deformation (J) with global spirometric and plethysmographic parameters, gas exchange, exercise capacity, dyspnoea, and disease stage in a prospective cohort study in 102 COPD patients. There were positive correlations of dHU, dsV, and J with spirometric variables, DLCO and gas exchange, 6-min walking distance, and negative correlations with plethysmographic lung volumes and indices of trapping and lung distension as well as GOLD stage. Stepwise regression identified FEV1/FVC (standardized ß = 0.429, p < 0.0001), RV/TLC (ß = -0.37, p < 0.0001), and BMI (ß = 0.27, p=<0.001) as the strongest predictors of CT intensity-based metrics dHU, with similar findings for dsV, while FEV1/FVC (ß = 0.32, p=<0.001) and RV/TLC (ß = -0.48, p=<0.0001) were identified as those for J. These data suggest that regional lung function is related to two major pathophysiological processes involved in global lung function deterioration in COPD: chronic airflow obstruction and gas trapping, with an additional contribution of nutritional status, which in turn determines respiratory muscle strength. Our data confirm previous findings in the literature, suggesting the potential of CT image-based regional lung function metrics as the biomarkers of disease severity and provide mechanistic insight into the interpretation of regional lung function indices in patients with COPD.

A machine learning approach to predict extreme inactivity in COPD patients using non-activity-related clinical data.

Facilitating the identification of extreme inactivity (EI) has the potential to improve morbidity and mortality in COPD patients. Apart from patients with obvious EI, the identification of a such behavior during a real-life consultation is unreliable. We therefore describe a machine learning algorithm to screen for EI, as actimetry measurements are difficult to implement. Complete datasets for 1409 COPD patients were obtained from COLIBRI-COPD, a database of clinicopathological data submitted by French pulmonologists. Patient- and pulmonologist-reported estimates of PA quantity (daily walking time) and intensity (domestic, recreational, or fitness-directed) were first used to assign patients to one of four PA groups (extremely inactive [EI], overtly active [OA], intermediate [INT], inconclusive [INC]). The algorithm was developed by (i) using data from 80% of patients in the EI and OA groups to identify 'phenotype signatures' of non-PA-related clinical variables most closely associated with EI or OA; (ii) testing its predictive validity using data from the remaining 20% of EI and OA patients; and (iii) applying the algorithm to identify EI patients in the INT and INC groups. The algorithm's overall error for predicting EI status among EI and OA patients was 13.7%, with an area under the receiver operating characteristic curve of 0.84 (95% confidence intervals: 0.75-0.92). Of the 577 patients in the INT/INC groups, 306 (53%) were reclassified as EI by the algorithm. Patient- and physician- reported estimation may underestimate EI in a large proportion of COPD patients. This algorithm may assist physicians in identifying patients in urgent need of interventions to promote PA.

Impact of Interface Type on Noninvasive Ventilation Efficacy in Patients With Neuromuscular Disease: A Randomized Cross-Over Trial.

BACKGROUND AND OBJECTIVE: Around 25% of patients with neuro-muscular diseases (NMD) are treated by home noninvasive ventilation (NIV) through an oronasal mask. However, there is growing evidence that nasal masks require lower NIV pressures and result in fewer residual obstructive events. We hypothesized that nasal masks would improve efficacy and reduce side effects compared to oronasal masks in this population. METHODS: open label, cross-over, randomized, study in 2 tertiary care hospitals. Patients with NMD treated by home NIV were randomized for one-week periods to nasal and oronasal interfaces respectively (cross-over). At the end of each period, nocturnal polygraphy (monitoring mouth opening) under NIV, synchronized with transcutaneous partial pressure in CO2 (tcCO2) was performed. Data were collected from the NIV built-in software and NIV side-effects were collected. Intention-to-treat and per protocol analyses were performed. The primary outcome was mean nocturnal SpO2. The secondary outcomes were: percentage of sleep with SpO2<90%, oxygen desaturation index (ODI), mean tcCO2, mean duration of mouth opening during sleep, level of non-intentional leaks and side-effects. RESULTS: Thirty patients with NMD were included. There were no between-group differences for either the primary or secondary outcomes. Post hoc comparisons showed that changing between interfaces reduced NIV efficacy: mean nocturnal SpO2 (p=0.04), ODI (p=0.01), mean tcCO2 (p=0.048), side-effects (p=0.008). CONCLUSION: Nasal masks did not improve NIV efficacy or reduce side effects compared to oronasal masks in patients with NMD treated by home NIV. The efficacy of NIV is reduced during the transition to another interface, requiring close monitoring. Registration number: NCT03458507.

Reduction in sympathetic tone in patients with obstructive sleep apnoea: is fixed CPAP more effective than APAP? A randomised, parallel trial protocol.

INTRODUCTION: Obstructive sleep apnoea (OSA) is a prevalent disease associated with cardiovascular events. Hypertension is one of the major intermediary mechanisms leading to long-term cardiovascular adverse events. Intermittent hypoxia and hypercapnia associated with nocturnal respiratory events stimulate chemoreflexes, resulting in sympathetic overactivity and blood pressure (BP) elevation. Continuous positive airway pressure (CPAP) is the primary treatment for OSA and induces a small but significant reduction in BP. The use of auto-adjusting positive airway pressure (APAP) has increased in the last years and studies showed different ranges of BP reduction when comparing both modalities. However, the pathophysiological mechanisms implicated are not fully elucidated. Variations in pressure through the night inherent to APAP may induce persistent respiratory efforts and sleep fragmentation that might impair sympathovagal balance during sleep and result in smaller decreases in BP. Therefore, this double-blind randomised controlled trial aims to compare muscle sympathetic nerve activity (MSNA) assessed by microneurography (reference method for measuring sympathetic activity) after 1 month of APAP versus fixed CPAP in treatment-naive OSA patients. This present manuscript describes the design of our study, no results are presented herein. and is registered under the below reference number. METHODS AND ANALYSIS: Adult subjects with newly diagnosed OSA (Apnoea-Hypopnoea Index >20/hour) will be randomised for treatment with APAP or fixed CPAP. Measurements of sympathetic activity by MSNA, heart rate variability and catecholamines will be obtained at baseline and after 30 days. The primary composite outcome will be the change in sympathetic tone measured by MSNA in bursts/min and bursts/100 heartbeats. Sample size calculation was performed with bilateral assumption. We will use the Student's t-test to compare changes in sympathetic tone between groups. ETHICS AND DISSEMINATION: The protocol was approved by The French Regional Ethics Committee. The study started in March 2018 with primary completion expected to March 2019. Dissemination plans of the results include presentations at conferences and publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03428516; Pre-results.

[Pathophysiology of obstructive sleep apnea syndrome and its cardiometabolic consequences]. / Physiopathologie du syndrome d'apnées-hypopnées obstructives du sommeil et de ses conséquences cardio-métaboliques.

Obstructive sleep apnoea syndrome (OSAS) is characterized by recurrent partial or complete pharyngeal collapses during sleep. The pathophysiology of OSAS is complex and multifactorial. Factors influencing upper airway patency include a reduction in upper airway dimensions that can result from both anatomical and functional alterations (obesity, fluid shift or maxillo-facial structural changes), and increased pharyngeal collapsibility owing to reduced neuromuscular compensation and lack of the pharyngeal protective reflex during sleep. Severe OSAS is associated with a high cardiometabolic risk. Obstructive apnoeic events incorporate a range of stressors that activate mechanisms contributing to the initiation and progression of cardiac, vascular and metabolic diseases. Obstructed breathing induces markedly negative intrathoracic pressure and also provokes hypoxia and hypercapnia. The hypoxaemic stress is further amplified by the subsequent reoxygenation (intermittent hypoxia), resulting in the generation of reactive oxygen species (ROS), sympathetic activation and inflammation. OSAS is able to increase the number of fatal and non-fatal cardiovascular events, including arrhythmias, myocardial infarction and stroke. OSAS is associated with dyslipidemia, type 2 diabetes, its poor control and non-alcoholic fatty liver disease. Screening, diagnosis and integrated care of OSAS should be included in an aggressive management of risk reduction in chronic cardiovascular and metabolic diseases.

[Obstructive sleep apnea syndrome. Diagnostic strategies in various clinical settings]. / Syndrome d'apnées du sommeil. Stratégies diagnostiques dans les différents contextes cliniques.

Obstructive Sleep Apnea Syndrome (OSAS) is a common disease, whose prevalence and expression may vary depending on the associated pathology, age or gender. Thus, the prevalence of OSAS is up to 80% in case of refractory hypertension. This led up to individualize clinical presentation of clusters, although currently, the individualization of these different phenotypes did not conduct to a specific care or predict different evolution. Offering the best strategy for the right patient remains an important objective. However, the frequent association of OSAS and various metabolic diseases, and thus induced cardiovascular risk factors, is to be considered in the therapeutic care and judgment of the response to established treatments. By acting on all components in pathological cause in these patients with OSAS, a combined support will thus permit optimal beneficial effect.

Obstructive Sleep Apnea: A Cluster Analysis at Time of Diagnosis.

BACKGROUND: The classification of obstructive sleep apnea is on the basis of sleep study criteria that may not adequately capture disease heterogeneity. Improved phenotyping may improve prognosis prediction and help select therapeutic strategies. OBJECTIVES: This study used cluster analysis to investigate the clinical clusters of obstructive sleep apnea. METHODS: An ascending hierarchical cluster analysis was performed on baseline symptoms, physical examination, risk factor exposure and co-morbidities from 18,263 participants in the OSFP (French national registry of sleep apnea). The probability for criteria to be associated with a given cluster was assessed using odds ratios, determined by univariate logistic regression. RESULTS: Six clusters were identified, in which patients varied considerably in age, sex, symptoms, obesity, co-morbidities and environmental risk factors. The main significant differences between clusters were minimally symptomatic versus sleepy obstructive sleep apnea patients, lean versus obese, and among obese patients different combinations of co-morbidities and environmental risk factors. CONCLUSIONS: Our cluster analysis identified six distinct clusters of obstructive sleep apnea. Our findings underscore the high degree of heterogeneity that exists within obstructive sleep apnea patients regarding clinical presentation, risk factors and consequences. This may help in both research and clinical practice for validating new prevention programs, in diagnosis and in decisions regarding therapeutic strategies.

Impact of Interface Type on Noninvasive Ventilation Efficacy in Patients With Neuromuscular Disease: A Randomized Cross-Over Trial / Impacto del tipo de mascarilla en la eficacia de la ventilación no invasiva en pacientes con enfermedad neuromuscular: un ensayo clínico aleatorizado cruzado

Background and objective: Around 25% of patients with neuro-muscular diseases (NMD) are treated by home noninvasive ventilation (NIV) through an oronasal mask. However, there is growing evidence that nasal masks require lower NIV pressures and result in fewer residual obstructive events. We hypothesized that nasal masks would improve efficacy and reduce side effects compared to oronasal masks in this population.Methods: open label, cross-over, randomized, study in 2 tertiary care hospitals. Patients with NMD treated by home NIV were randomized for one-week periods to nasal and oronasal interfaces respectively (cross-over). At the end of each period, nocturnal polygraphy (monitoring mouth opening) under NIV, synchronized with transcutaneous partial pressure in CO2 (tcCO2) was performed. Data were collected from the NIV built-in software and NIV side-effects were collected. Intention-to-treat and per protocol analyses were performed. The primary outcome was mean nocturnal SpO2. The secondary outcomes were: percentage of sleep with SpO2<90%, oxygen desaturation index (ODI), mean tcCO2, mean duration of mouth opening during sleep, level of non-intentional leaks and side-effects.Results: Thirty patients with NMD were included. There were no between-group differences for either the primary or secondary outcomes. Post hoc comparisons showed that changing between interfaces reduced NIV efficacy: mean nocturnal SpO2 (p=0.04), ODI (p=0.01), mean tcCO2 (p=0.048), side-effects (p=0.008). (AU)

Antecedentes y objetivo: Alrededor del 25% de los pacientes con enfermedades neuromusculares (ENM) son tratados mediante ventilación no invasiva (VNI) a través de una máscara oronasal. Sin embargo, existen crecientes indicios de que las máscaras nasales requieren presiones de VNI más bajas y resultan en menos eventos obstructivos residuales. Nuestra hipótesis fue que las máscaras nasales mejorarían la eficacia y reducirían los efectos secundarios en comparación con las máscaras oronasales en esta población.Métodos: Estudio abierto, cruzado, aleatorizado en 2 hospitales de atención terciaria. Los pacientes con ENM tratados mediante VNI domiciliaria fueron aleatorizados durante períodos de una semana de duración a las mascarillas nasales y oronasales, alternativamente (cruzado). Al final de cada período se realizó una polisomnografía nocturna (con monitorización de la apertura bucal) con VNI, sincronizada con la medición transcutánea de la presión parcial de CO2 (tcCO2). Los datos se recopilaron utilizando el software integrado en la VNI y se recogieron los efectos secundarios de la VNI. Se realizaron análisis por intención de tratar y por protocolo. El criterio de valoración principal fue la SpO2 nocturna media. Los criterios secundarios fueron: porcentaje de sueño con SpO2<90%, índice de desaturación de oxígeno (IDO), tcCO2 media, duración media de la apertura bucal durante el sueño, nivel de fugas no intencionales y efectos secundarios.Resultados: Se incluyeron 30 pacientes con ENM. No hubo diferencias entre los grupos para los resultados primarios o secundarios. Las comparaciones a posteriori mostraron que cambiar mascarillas reducía la eficacia de la VNI: SpO2 nocturna media (p=0,04), IDO (p=0,01), tcCO2 media (p=0,048) y efectos secundarios (p=0,008). (AU)

Nocturia is an independent predictive factor of prevalent hypertension in obstructive sleep apnea patients.

OBJECTIVE: The aim of this study was to determine whether nocturia is an independent predictor for prevalent hypertension in obstructive sleep apnea (OSA). METHODS: We analyzed data from a national prospective clinical cohort of OSA patients participating in the French national prospective registry. Anthropometric data, comorbidities, OSA severity, and number of voids/night were included in multivariate analyses to determine the independent variables associated with prevalent hypertension. RESULTS: A total of 22,674 OSA patients were included, of which 11,332 were hypertensive. The prevalence of hypertension among OSA patients was about 1.3 times higher in patients suffering from nocturia at 61.45% versus 46.52% in hypertensive and non-hypertensive OSA patients (p <0.001). There was a significant positive relationship between hypertension and the severity of nocturia beyond two voids/night: two voids/night versus none: odds ratio (OR) = 1.270 (95% confidence interval (CI) = 1.175; 1.372), three voids/night versus none: OR = 1.422 (95% CI = 1.293; 1.565), and four voids/night versus none: OR = 1.575 (95% CI = 1.394; 1.781). The strength of the association was enhanced in patients over 64 years of age. CONCLUSIONS: Nocturia is a strong independent predictor of prevalent hypertension in OSA. This association exhibited a "dose-response" relationship beyond two voids/night. The resolution of nocturia after continuous positive airway pressure (CPAP) treatment might be an important outcome to consider for the response of hypertension to CPAP.

Endoscopic volume reduction before or after lung transplantation.

Endobronchial valve therapy in patients with severe emphysema achieves similar clinical benefits to lung volume reduction surgery without the potential morbidity. We report successful endobronchial valve treatments in two patients with severe emphysema. Valves were placed in the first patient 5 months before lung transplantation and in the second patient 10 years after lung transplantation, using a flexible bronchoscope under local anaesthesia. The objective was to reduce pulmonary hyperinflation and improve lung function. The potential benefit of this procedure was anticipated by lobar collateral ventilation measurements. Two months later, forced expiratory volume in 1 s, forced vital capacity and dyspneoa improved in both cases.