Clinical correlates of respiratory disorders in patients with severe multiple sclerosis: A cross-sectional cohort.

BACKGROUND: Respiratory disorders remain incompletely described in multiple sclerosis (MS), even though they are a frequent cause of death. METHODS: The objective was to describe respiratory disorders in MS patients with Expanded Disability Status Score (EDSS) ⩾ 6.5. Diaphragm dysfunction was defined by at least two of the seven criteria: clinical signs, inspiratory recruitment of neck muscles during wakefulness, reduced upright vital capacity (VC) < 80%, upright-to-supine VC ⩾ 15% of upright VC, decrease in Maximal Inspiratory Pressure < 60%, phasic activation of inspiratory neck muscles during sleep, and opposition of thoracic and abdominal movements during sleep. Cough weakness was defined by a peak cough flow < 270 L/min and/or need for cough assist. Sleep apnea syndrome was defined by an apnea-hypopnea index ⩾ 15. RESULTS: Notably, 71 MS patients were included: median age 54 [48, 61] years; median disease duration 21.4 [16.0, 31.4] years. Of these, 52 patients had one or more respiratory disorders; diaphragm dysfunction was the most frequent (n = 34). Patients with diaphragm dysfunction and cough weakness were more disabled. The fatigue score and the cognitive evaluations did not differ between the groups. Five patients required non-invasive ventilation. CONCLUSION: Respiratory disorders are frequent in severe MS, mostly diaphragm dysfunction. Of interest, instrumental interventions are available to address these disorders.

Respiratory recovery trajectories after severe-to-critical COVID-19: a 1-year prospective multicentre study.

BACKGROUND: Survivors of severe-to-critical coronavirus disease 2019 (COVID-19) may have functional impairment, radiological sequelae and persistent symptoms requiring prolonged follow-up. This pragmatic study aimed to describe their clinical follow-up and determine their respiratory recovery trajectories, and the factors that could influence them and their health-related quality of life. METHODS: Adults hospitalised for severe-to-critical COVID-19 were evaluated at 3 months and up to 12 months post-hospital discharge in this prospective, multicentre, cohort study. RESULTS: Among 485 enrolled participants, 293 (60%) were reassessed at 6 months and 163 (35%) at 12 months; 89 (51%) and 47 (27%) of the 173 participants initially managed with standard oxygen were reassessed at 6 and 12 months, respectively. At 3 months, 34%, 70% and 56% of the participants had a restrictive lung defect, impaired diffusing capacity of the lung for carbon monoxide (D LCO) and significant radiological sequelae, respectively. During extended follow-up, both D LCO and forced vital capacity percentage predicted increased by means of +4 points at 6 months and +6 points at 12 months. Sex, body mass index, chronic respiratory disease, immunosuppression, pneumonia extent or corticosteroid use during acute COVID-19 and prolonged invasive mechanical ventilation (IMV) were associated with D LCO at 3 months, but not its trajectory thereafter. Among 475 (98%) patients with at least one chest computed tomography scan during follow-up, 196 (41%) had significant sequelae on their last images. CONCLUSIONS: Although pulmonary function and radiological abnormalities improved up to 1 year post-acute COVID-19, high percentages of severe-to-critical disease survivors, including a notable proportion of those managed with standard oxygen, had significant lung sequelae and residual symptoms justifying prolonged follow-up.

Screening for pulmonary arterial hypertension in adults carrying a BMPR2 mutation.

BACKGROUND: Heritable pulmonary arterial hypertension (PAH) is most commonly due to heterozygous mutations of the BMPR2 gene. Based on expert consensus, guidelines recommend annual screening echocardiography in asymptomatic BMPR2 mutation carriers. The main objectives of this study were to evaluate the characteristics of asymptomatic BMPR2 mutation carriers, assess their risk of occurrence of PAH and detect PAH at an early stage in this high-risk population. METHODS: Asymptomatic BMPR2 mutation carriers underwent screening at baseline and annually for a minimum of 2 years (DELPHI-2 study; ClinicalTrials.gov: NCT01600898). Annual screening included clinical assessment, ECG, pulmonary function tests, 6-min walk distance, cardiopulmonary exercise testing, chest radiography, echocardiography and brain natriuretic peptide (BNP) or N-terminal (NT)-proBNP level. Right heart catheterisation (RHC) was performed based on predefined criteria. An optional RHC at rest and exercise was proposed at baseline. RESULTS: 55 subjects (26 males; median age 37 years) were included. At baseline, no PAH was suspected based on echocardiography and NT-proBNP levels. All subjects accepted RHC at inclusion, which identified two mild PAH cases (3.6%) and 12 subjects with exercise pulmonary hypertension (21.8%). At long-term follow-up (118.8 patient-years of follow-up), three additional cases were diagnosed, yielding a PAH incidence of 2.3% per year (0.99% per year in males and 3.5% per year in females). All PAH cases remained at low-risk status on oral therapy at last follow-up. CONCLUSIONS: Asymptomatic BMPR2 mutation carriers have a significant risk of developing incident PAH. International multicentre studies are needed to confirm that refined multimodal screening programmes with regular follow-up allow early detection of PAH.

Intensity and quality of exertional dyspnoea in patients with stable pulmonary hypertension.

Dynamic hyperinflation is observed during exercise in 60% of patients with clinically stable pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH), intensifying exertional dyspnoea. The impact of dynamic changes in respiratory mechanics during exercise on qualitative dimensions of dyspnoea in these patients has not been evaluated.26 patients (PAH n=17; CTEPH n=9) performed an incremental symptom-limited cycle exercise test. Minute ventilation (V'E), breathing pattern, operating lung volumes and dyspnoea intensity were assessed throughout exercise. Dyspnoea quality was serially assessed during exercise using a three-item questionnaire (dyspnoea descriptors). The inflection point of tidal volume (V T) relative to V'E was determined for each incremental test. Changes in inspiratory capacity during exercise defined two groups of patients: hyperinflators (65%) and non-hyperinflators (35%). Multidimensional characterisation of dyspnoea was performed after exercise using the Multidimensional Dyspnea Profile.In hyperinflators, inspiratory capacity decreased progressively throughout exercise by 0.36 L, while remaining stable in non-hyperinflators. The "work/effort" descriptor was most frequently selected throughout exercise in both types of patients (65% of all responses). At the V T/V'E inflection, work/effort plateaued while "unsatisfied inspiration" descriptors became selected predominantly only in hyperinflators (77% of all responses). In the affective domain, the emotion most frequently associated with dyspnoea was anxiety.In pulmonary hypertension patients who develop hyperinflation during exercise, dyspnoea descriptors referring to unsatisfied inspiration become predominant following the V T/V'E inflection. As these descriptors are generally associated with more negative emotional experiences, delaying or preventing the V T/V'E inflection may have important implications for symptom management in patients with pulmonary hypertension.

Decreased respiratory-related postural perturbations at the cervical level under cognitive load.

PURPOSE: In healthy humans, postural and respiratory dynamics are intimately linked and a breathing-related postural perturbation is evident in joint kinematics. A cognitive dual-task paradigm that is known to induce both postural and ventilatory disturbances can be used to modulate this multijoint posturo-ventilatory (PV) interaction, particularly in the cervical spine, which supports the head. The objective of this study was to assess this modulation. METHODS: With the use of optoelectronic sensors, the breathing profile, articular joint motions of the cervical spine, hip, knees and ankles, and centre of pressure (CoP) displacement were measured in 20 healthy subjects (37 years old [29; 49], 10 females) during natural breathing (NB), a cognitive dual task (COG), and eyes-closed and increased-tidal-volume conditions. The PV interaction in the CoP and joint motions were evaluated by calculating the respiratory emergence (REm). RESULTS: Only the COG condition induced a decrease in the cervical REm (NB: 17.2% [7.8; 37.2]; COG: 4.2% [1.8; 10.0] p = 0.0020) concurrent with no changes in the cervical motion. The CoP REm (NB: 6.2% [3.8; 10.3]; COG: 12.9% [5.8; 20.7] p = 0.0696) and breathing frequency (NB: 16.6 min-1 [13.3; 18.7]; COG: 18.6 min-1 [16.3; 19.4] p = 0.0731) tended to increase, while the CoP (p = 0.0072) and lower joint motion displacements (p < 0.05) increased. CONCLUSION: This study shows stable cervical spine motion during a cognitive dual task, as well as increased postural perturbations globally and in other joints. The concurrent reduction in the PV interaction at the cervical spine suggests that this "stabilization strategy" is centrally controlled and is achieved by a reduction in the breathing-related postural perturbations at this level. Whether this strategy is a goal for maintaining balance remains to be studied.

ERS statement on respiratory muscle testing at rest and during exercise.

Assessing respiratory mechanics and muscle function is critical for both clinical practice and research purposes. Several methodological developments over the past two decades have enhanced our understanding of respiratory muscle function and responses to interventions across the spectrum of health and disease. They are especially useful in diagnosing, phenotyping and assessing treatment efficacy in patients with respiratory symptoms and neuromuscular diseases. Considerable research has been undertaken over the past 17 years, since the publication of the previous American Thoracic Society (ATS)/European Respiratory Society (ERS) statement on respiratory muscle testing in 2002. Key advances have been made in the field of mechanics of breathing, respiratory muscle neurophysiology (electromyography, electroencephalography and transcranial magnetic stimulation) and on respiratory muscle imaging (ultrasound, optoelectronic plethysmography and structured light plethysmography). Accordingly, this ERS task force reviewed the field of respiratory muscle testing in health and disease, with particular reference to data obtained since the previous ATS/ERS statement. It summarises the most recent scientific and methodological developments regarding respiratory mechanics and respiratory muscle assessment by addressing the validity, precision, reproducibility, prognostic value and responsiveness to interventions of various methods. A particular emphasis is placed on assessment during exercise, which is a useful condition to stress the respiratory system.

Ventilatory response to exercise in cardiopulmonary disease: the role of chemosensitivity and dead space.

The lungs and heart are irrevocably linked in their oxygen (O2) and carbon dioxide (CO2) transport functions. Functional impairment of the lungs often affects heart function and vice versa The steepness with which ventilation (V'E) rises with respect to CO2 production (V'CO2 ) (i.e. the V'E/V'CO2 slope) is a measure of ventilatory efficiency and can be used to identify an abnormal ventilatory response to exercise. The V'E/V'CO2 slope is a prognostic marker in several chronic cardiopulmonary diseases independent of other exercise-related variables such as peak O2 uptake (V'O2 ). The V'E/V'CO2 slope is determined by two factors: 1) the arterial CO2 partial pressure (PaCO2 ) during exercise and 2) the fraction of the tidal volume (VT) that goes to dead space (VD) (i.e. the physiological dead space ratio (VD/VT)). An altered PaCO2 set-point and chemosensitivity are present in many cardiopulmonary diseases, which influence V'E/V'CO2 by affecting PaCO2 Increased ventilation-perfusion heterogeneity, causing inefficient gas exchange, also contributes to the abnormal V'E/V'CO2 observed in cardiopulmonary diseases by increasing VD/VT During cardiopulmonary exercise testing, the PaCO2 during exercise is often not measured and VD/VT is only estimated by taking into account the end-tidal CO2 partial pressure (PETCO2 ); however, PaCO2 is not accurately estimated from PETCO2 in patients with cardiopulmonary disease. Measuring arterial gases (PaO2 and PaCO2 ) before and during exercise provides information on the real (and not "estimated") VD/VT coupled with a true measure of gas exchange efficiency such as the difference between alveolar and arterial O2 partial pressure and the difference between arterial and end-tidal CO2 partial pressure during exercise.

Effects of non-fatiguing respiratory muscle loading induced by expiratory flow limitation during strenuous incremental cycle exercise on metabolic stress and circulating natural killer cells.

Exercise induces release of cytokines and increase of circulating natural killers (NK) lymphocyte during strong activation of respiratory muscles. We hypothesised that non-fatiguing respiratory muscle loading during exercise causes an increase in NK cells and in metabolic stress indices. Heart rate (HR), ventilation (VE), oesophageal pressure (Pes), oxygen consumption (VO2), dyspnoea and leg effort were measured in eight healthy humans (five men and three women, average age of 31 ± 4 years and body weight of 68 ± 10 kg), performing an incremental exercise testing on a cycle ergometer under control condition and expiratory flow limitation (FL) achieved by putting a Starling resistor. Blood samples were obtained at baseline, at peak of exercise and at iso-workload corresponding to that reached at the peak of FL exercise during control exercise. Diaphragmatic fatigue was evaluated by measuring the tension time index of the diaphragm. Respiratory muscle overloading caused an earlier interruption of exercise. Diaphragmatic fatigue did not occur in the two conditions. At peak of flow-limited exercise compared to iso-workload, HR, peak inspiratory and expiratory Pes, NK cells and norepinephrine were significantly higher. The number of NK cells was significantly related to ΔPes (i.e. difference between the most and the less negative Pes) and plasmatic catecholamines. Loading of respiratory muscles is able to cause an increase of NK cells provided that activation of respiratory muscles is intense enough to induce a significant metabolic stress.

An official European Respiratory Society statement: pulmonary haemodynamics during exercise.

There is growing recognition of the clinical importance of pulmonary haemodynamics during exercise, but several questions remain to be elucidated. The goal of this statement is to assess the scientific evidence in this field in order to provide a basis for future recommendations.Right heart catheterisation is the gold standard method to assess pulmonary haemodynamics at rest and during exercise. Exercise echocardiography and cardiopulmonary exercise testing represent non-invasive tools with evolving clinical applications. The term "exercise pulmonary hypertension" may be the most adequate to describe an abnormal pulmonary haemodynamic response characterised by an excessive pulmonary arterial pressure (PAP) increase in relation to flow during exercise. Exercise pulmonary hypertension may be defined as the presence of resting mean PAP <25 mmHg and mean PAP >30 mmHg during exercise with total pulmonary resistance >3 Wood units. Exercise pulmonary hypertension represents the haemodynamic appearance of early pulmonary vascular disease, left heart disease, lung disease or a combination of these conditions. Exercise pulmonary hypertension is associated with the presence of a modest elevation of resting mean PAP and requires clinical follow-up, particularly if risk factors for pulmonary hypertension are present. There is a lack of robust clinical evidence on targeted medical therapy for exercise pulmonary hypertension.

Asymptomatic subjects with airway obstruction have significant impairment at exercise.

BACKGROUND: The relevance of screening for airway obstruction in subjects not complaining of COPD symptoms may depend on the definition of airway obstruction. Response to exercise in asymptomatic subjects with persistent airway obstruction as defined by a postbronchodilator FEV1/FVC <5th centile lower limit of normal (LLN) remains unknown. METHODS: Dyspnoea (Borg scale), exercise tolerance and ventilatory constraints on tidal volume expansion were assessed in 20 consecutive asymptomatic subjects with persistent mild airway obstruction detected by screening (postbronchodilator FEV1/FVC z-score: -2.14±0.29; FEV1 z-score: -1.02±0.64) undergoing incremental cycle cardiopulmonary exercise testing, compared with 20 healthy controls with normal spirometry matched for age, sex, body mass index and smoking history (FEV1/FVC z-score: -0.13±0.57; FEV1 z-score: 0.32±0.67) and with 20 symptomatic patients with COPD matched for the same characteristics (FEV1/FVC z-score: -2.36±0.51; FEV1 z-score: -1.02±0.48). RESULTS: Asymptomatic subjects with airway obstruction had higher dyspnoea ratings than controls during incremental exercise. Asymptomatic subjects with airway obstruction had also peak oxygen consumption and peak power output that were lower than controls, and similar to those observed in patients with COPD. Although less frequent than in COPD, dynamic hyperinflation was more frequent in asymptomatic subjects with airway obstruction than in controls (85%, 50% and 10%, respectively; p=0.01 in asymptomatic subjects vs controls and p=0.04 vs COPD). CONCLUSIONS: Although they did not present with chronic activity-related dyspnoea, subjects with a postbronchodilator FEV1/FVC

Use of exercise testing in the evaluation of interventional efficacy: an official ERS statement.

This document reviews 1) the measurement properties of commonly used exercise tests in patients with chronic respiratory diseases and 2) published studies on their utilty and/or evaluation obtained from MEDLINE and Cochrane Library searches between 1990 and March 2015.Exercise tests are reliable and consistently responsive to rehabilitative and pharmacological interventions. Thresholds for clinically important changes in performance are available for several tests. In pulmonary arterial hypertension, the 6-min walk test (6MWT), peak oxygen uptake and ventilation/carbon dioxide output indices appear to be the variables most responsive to vasodilators. While bronchodilators do not always show clinically relevant effects in chronic obstructive pulmonary disease, high-intensity constant work-rate (endurance) tests (CWRET) are considerably more responsive than incremental exercise tests and 6MWTs. High-intensity CWRETs need to be standardised to reduce interindividual variability. Additional physiological information and responsiveness can be obtained from isotime measurements, particularly of inspiratory capacity and dyspnoea. Less evidence is available for the endurance shuttle walk test. Although the incremental shuttle walk test and 6MWT are reliable and less expensive than cardiopulmonary exercise testing, two repetitions are needed at baseline. All exercise tests are safe when recommended precautions are followed, with evidence suggesting that no test is safer than others.

Multidimensional approach to dyspnea.

PURPOSE OF REVIEW: This review focuses on sensory-perceptual and affective/emotional domains of dyspnea. RECENT FINDINGS: Recent studies have underscored the multidimensional aspect of dyspnea, which comprises three major dimensions: the sensory-perceptual domain, the affective distress, and the symptom impact or burden. Sensory-perceptual dimension includes ratings of dyspnea intensity and its quality, that is, 'how breathing feels like.' Affective distress addresses the question of 'how distressing breathing is' and focuses on the perception of immediate unpleasantness or the cognitive evaluative response about the potential consequence of what is perceived. Symptom impact evaluates how dyspnea impacts on functional ability/disability, health status, and/or quality of life. SUMMARY: Dyspnea is a debilitating symptom and the major reason for seeking medical attention in patients with cardiorespiratory diseases. Dyspnea predicts morbidity, quality of life, and mortality in several different conditions. Notwithstanding sometimes patients neglect to report dyspnea to their clinician because they feel it is not sufficiently relevant to be documented. The relationship between what the patients feel, how they express themselves about the disease, and how caregivers interpret their complaints is complex and not easy to decipher. It is important to correctly recognize dyspnea, and optimize and individualize its clinical management.

Relationship between daily physical activity and aerobic fitness in adults with cystic fibrosis.

BACKGROUND: The best clinical practice to investigate aerobic fitness includes measurements obtained during cardiopulmonary exercise testing (CPET), however it remains an underutilised clinical measure in cystic fibrosis (CF). To investigate this further, different methods of quantifying exercise capacity in CF are required. The possibility that measuring physical activity (PA) by a portable accelerometer could be used to assess the CF aerobic state and could be added among the CPET surrogates has not been investigated. The aim of this study was to examine the relationship between PA and exercise fitness both at submaximal and maximal levels in clinically stable adults with CF. METHODS: Thirty CF patients (FEV1 71 ± 19% predicted) and fifteen healthy controls undertook an incremental CPET on a cycle ergometer. CPET-related measurements included: oxygen uptake (V'O2), carbon dioxide production (V'CO2), ventilatory profile, heart rate (HR) and oxygen pulse (V'O2/HR) throughout exercise and at lactic threshold (LT) and peak. LT measures represent submaximal exercise related data. PA was assessed using the accelerometer SenseWear Pro3 Armband. RESULTS: Moderate (>4.8 metabolic equivalents (METS)) and moderate + vigorous (>7.2 METS) PA was related to V'O2 (p = 0.005 and p = 0.009, respectively) and work rate (p = 0.004 and p = 0.002, respectively) at LT. Moderate PA or greater was positively related to peak V'O2 (p = 0.005 and p = 0.003, respectively). Daily PA levels were similar in CF and healthy controls. Except for peak values, V'O2 profile and the V'O2 at LT were comparable between CF and healthy controls. CONCLUSIONS: In adult CF patients daily PA positively correlated with aerobic capacity. PA measurements are a valuable tool in the assessment of exercise performance in an adult CF population and could be used for interventional exercise trials to optimize exercise performance and health status. PA levels and parameters obtained at submaximal exercise are similar in CF and in healthy controls.

Dyspnoea: a multidimensional and multidisciplinary approach.

Dyspnoea is a debilitating symptom that affects quality of life, exercise tolerance and mortality in various disease conditions/states. In patients with chronic obstructive pulmonary disease (COPD), it has been shown to be a better predictor of mortality than forced expiratory volume in 1 s. In patients with heart disease it is a better predictor of mortality than angina. Dyspnoea is also associated with decreased functional status and worse psychological health in older individuals living at home. It also contributes to the low adherence to exercise training programmes in sedentary adults and in COPD patients. The mechanisms of dyspnoea are still unclear. Recent studies have emphasised the multidimensional nature of dyspnoea in the sensory-perceptual (intensity and quality), affective distress and impact domains. The perception of dyspnoea involves a complex chain of events that depend on varying cortical integration of several afferent/efferent signals and coloured by affective processing. This review, which stems from the European Respiratory Society research symposium held in Paris, France in November 2012, aims to provide state-of-the-art advances on the multidimensional and multidisciplinary aspects of dyspnoea, by addressing three different themes: 1) the neurophysiology of dyspnoea, 2) exercise and dyspnoea, and 3) the clinical impact and management of dyspnoea.

Dynamic respiratory mechanics and exertional dyspnoea in pulmonary arterial hypertension.

Patients with pulmonary arterial hypertension (PAH) may exhibit reduced expiratory flows at low lung volumes, which could promote exercise-induced dynamic hyperinflation (DH). This study aimed to examine the impact of a potential exercise-related DH on the intensity of dyspnoea in patients with PAH undergoing symptom-limited incremental cardiopulmonary cycle exercise testing (CPET). 25 young (aged mean±sd 38±12 yrs) nonsmoking PAH patients with no evidence of spirometric obstruction and 10 age-matched nonsmoking healthy subjects performed CPET to the limit of tolerance. Ventilatory pattern, operating lung volumes (derived from inspiratory capacity (IC) measurements) and dyspnoea intensity (Borg scale) were assessed throughout CPET. IC decreased (i.e. DH) progressively throughout CPET in PAH patients (average 0.15 L), whereas it increased in all the healthy subjects (0.45 L). Among PAH patients, 15 (60%) exhibited a decrease in IC throughout exercise (average 0.50 L), whereas in the remaining 10 (40%) patients IC increased (average 0.36 L). Dyspnoea intensity and ventilation were greater in PAH patients than in controls at any stage of CPET, whereas inspiratory reserve volume was lower. We conclude that DH-induced mechanical constraints and excessive ventilatory demand occurred in these young nonsmoking PAH patients with no spirometric obstruction and was associated with exertional dyspnoea.

Intrapulmonary distribution of blood flow during exercise in pulmonary hypertension assessed by a new combination technique.

Background: Hyperventilation and inadequate cardiac output (CO) increase are the main causes of exercise limitation in pulmonary hypertension (PH). Intrapulmonary blood flow partitioning between ventilated and unventilated lung zones is unknown. Thoracic impedance cardiography and inert gas rebreathing have been both validated in PH patients for non-invasive measurement of CO and pulmonary blood flow (PBF), respectively. This study sought to evaluate CO behaviour in PH patients during exercise and its partitioning between ventilated and unventilated lung areas, in parallel with ventilation partitioning between ventilated and unventilated lung zones. Methods: Eighteen PH patients (group 1 or 4) underwent a cardiopulmonary exercise test (CPET) with a three-step loaded workload protocol. The steps occurred at 0%, 20%, 40%, and 60% of peak workload reached during a preliminary maximum CPET. Ventilatory parameters, arterial blood gases, CO, PBF, and intrapulmonary shunt (calculated as the difference between CO and PBF) were obtained at each step, combining thoracic impedance cardiography and an inert gas rebreathing technique. Results: Dead space ventilation observed throughout the exercise was about 40% of total ventilation. A progressive increase of CO from 4.86 ± 1.24 L/min (rest) to 9.41 ± 2.63 L/min (last step), PBF from 3.81 ± 1.41 L/min to 7.21 ± 2.93 L/min, and intrapulmonary shunt from 1.05 ± 0.96 L/min to 2.21 ± 2.28 L/min was observed. Intrapulmonary shunt was approximately 20% of CO at each exercise step. Conclusions: Although the study population was small, the combined non-invasive CO measurement seems a promising tool for deepening our knowledge of lung exercise haemodynamics in PH patients. This technique could be applied in future studies to evaluate PH treatment influences on CO partitioning, since a secondary increase of intrapulmonary shunt is undesirable.

What to expect from the ERS International Congress 2023.

This article provides an overview of the reasons to attend the 2023 ERS Congress, including a summary of the ECM session and the NEXT programme. https://bit.ly/46ghP4g.