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Anne-Catherine Maynard-Paquette,1 Claude Poirier,2 Carl Chartrand-Lefebvre,3,4 Bruno-Pierre Dubé2,5 1Centre Hospitalier de l’Université de Montréal (CHUM), Montreal, Quebec, Canada; 2Centre Hospitalier de l’Université de Montréal (CHUM), Department of Medicine, Respiratory Medicine Division, Montreal, Quebec, Canada; 3Centre Hospitalier de l’Université de Montréal (CHUM), Department of Radiology, Montréal, Québec, Canada; 4Research Center of the CHUM (CRCHUM) – Imaging and Engineering Axis, Montreal, Quebec, Canada; 5Research Center of the CHUM (CRCHUM) - Health Innovation and Evaluation Hub, Montreal, Quebec, CanadaCorrespondence: Bruno-Pierre DubéCentre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), 850 Rue St-Denis, Montréal, Qc H2X0A9, CanadaTel +1 514 890-8000Email bruno-pierre.dube@umontreal.caRationale: Chronic obstructive pulmonary disease (COPD) is associated with changes in the composition and function of peripheral and respiratory muscles, which can negatively impact quality of life. Ultrasonography can provide a non-invasive evaluation of the integrity of both peripheral muscles and diaphragm, but its use in patients with COPD is still being investigated. We aimed at evaluating the relationship between quadriceps size, using ultrasonography and symptoms, lung function and diaphragm contractility in a cohort of patients with COPD.Methods: COPD patients were prospectively recruited and ultrasonography of the dominant quadriceps and of the diaphragm was performed. Quadriceps size was evaluated using three measurements: 1) cross-sectional area of the rectus femoris (Qcsa), 2) thickness (Qthick) and 3) contractile index (Qci), defined as the ratio of quadriceps thickness/total anterior thigh thickness. Diaphragm contractility was evaluated using thickening fraction (TFdi). Clinical characteristics and number of moderate-to-severe exacerbations in the previous year were retrieved from medical files. Dyspnea (mMRC scale) and disease impact on health status (COPD Assessment Test (CAT)) were measured at inclusion. Fat-free mass index (FFMI) was assessed using bioelectrical impedance.Results: Forty patients were recruited (20 males, mean age and FEV1 66±6 years and 49±17%predicted, respectively). Mean Qcsa, Qthick and Qci were 336±145 mm2, 1.55±0.53 cm and 64±16%, respectively, and mean TFdi was 91±36%. Qci was significantly correlated with FFMI (rho=0.59, p=0.001), TFdi (rho=0.41, p=0.008), FEV1 (rho=0.43, p=0.001) but not with age (rho=0.18, p=0.28). Qci was significantly correlated to CAT score (rho=−0.47, p=0.002), even when controlled for FEV1, and was lower in patients with an mMRC score ≥2 (55±15 vs 70±14%, p=0.002). Qcsa and Qci were significantly lower in patients with frequent exacerbations. In a multiple linear regression analysis that included age, gender, FFMI, FEV1 and TFdi, only FFMI and TFdi were found to be significantly related to lower Qci values.Conclusion: In patients with COPD, ultrasound evaluation of the quadriceps contractile index is feasible and related to disease severity, clinical symptoms, exacerbation history and diaphragm contractility. As such, it may provide a novel tool for the evaluation of the severity and burden of the disease in this population. Further studies are required to better delineate its potential role as a prognostic marker in this population.Keywords: COPD, ultrasound, quadriceps, diaphragm, contractile index

Introduction: Smokers frequently display respiratory symptoms despite the fact that their pulmonary function tests (PFTs) can be normal. Quantitative lung ventilation single-photon emission computed tomography (SPECT/CT) can provide a quantification of lung ventilatory homogeneity and could prove useful as an early marker of airway disease in smokers. We measured the effects of smoking on regional ventilation distribution in subjects with normal lung function and evaluated whether ventilation distribution in these subjects is related to lung function tests results and clinical symptoms., Methods: Subjects without any history of respiratory disease were prospectively recruited and separated in two groups: active smokers (AS: ≥10 cigarettes/day and history of ≥15 pack-years) and never smokers (NS: lifetime exposure of <5 cigarettes). All subjects performed PFTs (which had to be normal, defined as z-score values of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, total lung capacity (TLC) residual volume and diffusion capacity (DLCO) all falling between -1.65 and +1.65) and underwent SPECT/CT with Technegas, which generated subject- specific ventilation heterogeneity maps. The area under the compensated coefficient of variation (CV) density curve for CV values > 40%, (AUC-CV40%) was used as the measure of ventilation heterogeneity., Results: 30 subjects were recruited (15 per group). Subjects in the AS group displayed higher dyspnea levels (1 [1-2] vs. 0 [0-1] units on mMRC scale, p < 0.001). AUC- CV40% was significantly higher in the AS group (0.386 ± 0.106 vs. 0.293 ± 0.069, p = 0.004). AUC-CV40% was significantly correlated to FEV1 (rho = -0.47, p = 0.009), DLCO (rho = -0.49, p = 0.006), CAT score (rho = 0.55, p = 0.002) and mMRC score (rho = 0.54, p = 0.002). Subjects with mMRC >0 had higher AUC-CV40% values than those without dyspnea (0.289 ± 0.071 vs. 0.378 ± 0.102, p = 0.006), while FEV1 and DLCO were not different between those groups. ROC analyses showed that the AUC for AUC-CV40% in identifying subjects with mMRC score >0 was 0.78 (95%CI 0.61-0.95, p = 0.009), which was significantly higher than that of FEV1 and DLCO., Discussion: In smokers with normal lung function, ventilatory inhomogeneities can be quantified using SPECT/CT. AUC-CV40% values are related to lung function decline and to respiratory symptomatology, suggesting a potential role for this marker in the evaluation of symptomatic smokers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Juneau, Leblond, Chatta, Lévesque, Lussier and Dubé.)

Background: Shrinking lung syndrome (SLS) is a rare manifestation of systemic lupus erythematosus (SLE) characterized by decreased lung volumes and diaphragmatic weakness in a dyspneic patient. Chest wall dysfunction secondary to pleuritis is the most commonly proposed cause. In this case report, we highlight a new potential mechanism of SLS in SLE, namely diaphragmatic weakness associated with myositis with CD20 positive B-cell aggregates., Case Presentation: A 51-year-old Caucasian woman was diagnosed with SLE and secondary Sjögren's syndrome based on a history of pleuritis, constrictive pericarditis, polyarthritis, photosensitivity, alopecia, oral ulcers, xerophthalmia and xerostomia. Serologies were significant for positive antinuclear antibodies, anti-SSA, lupus anticoagulant and anti-cardiolopin. Blood work revealed a low C3 and C4, lymphopenia and thrombocytopenia. She was treated with with low-dose prednisone and remained in remission with oral hydroxychloroquine. Seven years later, she developed mild proximal muscle weakness and exertional dyspnea. Pulmonary function testing revealed a restrictive pattern with small lung volumes. Pulmonary imaging showed elevation of the right hemidiaphragm without evidence of interstitial lung disease. Diaphragmatic ultrasound was suggestive of profound diaphragmatic weakness and dysfunction. Based on these findings, a diagnosis of SLS was made. Her proximal muscle weakness was investigated, and creatine kinase (CK) levels were normal. Electromyography revealed fibrillation potentials in the biceps, iliopsoas, cervical and thoracic paraspinal muscles, and complex repetitive discharges in cervical paraspinal muscles. Biceps muscle biopsy revealed dense endomysial lymphocytic aggregates rich in CD20 positive B cells, perimysial fragmentation with plasma cell-rich perivascular infiltrates, diffuse sarcolemmal upregulation of class I MHC, perifascicular upregulation of class II MHC, and focal sarcolemmal deposition of C5b-9. Treatment with prednisone 15 mg/day and oral mycophenolate mofetil 2 g/day was initiated. Shortness of breath and proximal muscle weakness improved significantly., Conclusion: Diaphragmatic weakness was the inaugural manifestation of myositis in this patient with SLE. The spectrum of myologic manifestations of myositis with prominent CD20 positive B-cell aggregates in SLE now includes normal CK levels and diaphragmatic involvement, in association with SLS., (© 2021. The Author(s).)

Introduction: In patients with cystic fibrosis (CF), the monitoring of respiratory muscle activity using electromyography can provide information on the demand-to-capacity ratio of the respiratory system and act as a clinical marker of disease activity, but this technique is not adapted to routine clinical care. Ultrasonography of the diaphragm could provide an alternative, simpler and more widely available alternative allowing the real-time assessment of the diaphragm contractile reserve (DCR), but its relationship with recognized markers of disease severity and clinical outcomes are currently unknown. Methods: Stable patients with CF were prospectively recruited. Diaphragm ultrasound was performed and compared to forced expiratory volume in 1 s (FEV 1 ), residual volume (RV), handgrip strength, fat-free mass index (FFMI), serum vitamin levels, dyspnea levels and rate of acute exacerbation (AE). Diaphragm activity was reported as DCR (the ratio of tidal-to-maximal thickening fractions, representing the remaining diaphragm contractility available after tidal inspiration) and TFmax (representing maximal diaphragm contractile strength). Inter-observer reliability of the measurement of DCR was evaluated using intra-class correlation analysis. Results: 110 patients were included [61 males, median (interquartile range), age 31 (27-38) years, FEV 1 66 (46-82)% predicted]. DCR was significantly correlated to FEV 1 (rho = 0.46, p < 0.001), RV (rho = -0.46, p < 0.001), FFMI (rho = 0.41, p < 0.001), and handgrip strength (rho = 0.22, p = 0.02), but TFmax was not. In a multiple linear regression analysis, both RV and FFMI were independent predictors of DCR. DCR, but not TFmax, was statistically lower in patients with > 2 exacerbations/year (56 ± 25 vs. 71 ± 17%, p = 0.001) and significantly lower with higher dyspnea levels. A ROC analysis showed that DCR performed better than FEV 1 (mean difference in AUROC 0.09, p = 0.04), RV (mean difference in AUROC 0.11, p = 0.03), and TFmax at identifying patients with an mMRC score > 2. Inter-observer reliability of DCR was high (ICC = 0.89, 95% CI 0.84-0.92, p < 0.001). Conclusion: In patients with CF, DCR is a reliable and non-invasive marker of disease severity that is related to respiratory and extra-pulmonary manifestations of the disease and to clinical outcomes. Future studies investigating the use of DCR as a longitudinal marker of disease progression, response to interventions or target for therapy would further validate its translation into clinical practice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gabrysz-Forget, Maynard-Paquette, Kharat, Tremblay, Silviet-Carricart, Lavoie, Girard and Dubé.)

Rationale: Sitting-to-supine fall in vital capacity (ΔVC) can be used to help identify diaphragm dysfunction (DD), but its optimal predictive threshold value is uncertain. Our aim was to evaluate the diagnostic performance of ΔVC in identifying the presence of unilateral or bilateral DD., Methods: Patients referred to the diaphragm dysfunction clinic of our center (2017-2018) were included. All subjects had lung function testing (including measurement of ΔVC) and an ultrasound assessment of diaphragm thickening fraction (TFdi). Unilateral DD was defined as a single hemidiaphragm with TFdi ≤30 % and bilateral DD as a mean TFdi value of both hemidiaphragms ≤30 %. Clinical and physiological characteristics were compared across groups, and sensitivity/specificity analyses of ΔVC to identify DD were performed., Results: 84 patients were included (31 unilateral DD, 17 bilateral DD and 36 without significant DD). DD groups had similar age, gender and BMI (all p > 0.05), but patients with bilateral DD had lower FVC, FEV1, MIP, TLC, ΔVC and more frequent orthopnea than patients with unilateral DD (all p < 0.05). There was a significant correlation between TFdi and ΔVC (rho=-0.56, p < 0.001). The optimal ΔVC value to identify bilateral DD was ≤-15 % [AUC 0.97 (95 %CI 0.89-1.00), p < 0.001, with sensitivity and specificity of 100 % and 89 %, respectively]. No single threshold of ΔVC could accurately predict unilateral DD [AUC 0.58 (95 %CI 0.45-0.72), p = 0.24]., Conclusion: ΔVC performs poorly in identifying patients with unilateral DD. However, a ΔVC value ≤-15 % is strongly associated with the presence of bilateral DD. These findings should be taken into account when using ΔVC in the evaluation of patients with suspected DD., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: We evaluated the functional consequences of diaphragm involvement in patients with inclusion body myositis (IBM)., Methods: Ultrasound diaphragm thickening fraction (TFdi), lung function and dyspnea levels were compared between IBM patients and matched controls. Patients with IBM were grouped into "low" and "high" diaphragm activity based on TFdi values (with cutoff value being the lowest observed TFdi in the control group), and clinical characteristics were compared between groups., Results: 20 IBM patients were included. TFdi was significantly lower in patients and correlated with time since symptom onset (rho = 0.74, P < .001). Patients had significantly lower forced vital capacity and higher dyspnea scores than controls. IBM patients with "low" diaphragm activity (n = 9) had lower 6-min walking distance, higher resting and exertional dyspnea and a larger positional decrease in vital capacity (all P ≤ .03) than patients with 'high' activity. Timed Up and Go time and St. George's Respiratory Questionnaire were not different between groups., Conclusions: Diaphragm involvement in IBM is related to disease duration and has detrimental effects on lung function, dyspnea and exercise capacity. Further studies are required to investigate its potential as a therapeutic target., (© 2021 Wiley Periodicals LLC.)

Background: The assessment of diaphragm function with diaphragm ultrasound seems to bring important clinical information to describe diaphragm work and weakness. When the diaphragm is weak, extradiaphragmatic muscles may play an important role, but whether ultrasound can also assess their activity and function is unknown. This study aimed to (1) evaluate the feasibility of measuring the thickening of the parasternal intercostal and investigate the responsiveness of this muscle to assisted ventilation; and (2) evaluate whether a combined evaluation of the parasternal and the diaphragm could predict failure of a spontaneous breathing trial., Methods: First, an exploratory evaluation of the parasternal in 23 healthy subjects. Second, the responsiveness of parasternal to several pressure support levels were studied in 16 patients. Last, parasternal activity was compared in presence or absence of diaphragm dysfunction (assessed by magnetic stimulation of the phrenic nerves and ultrasound) and in case of success/failure of a spontaneous breathing trial in 54 patients., Results: The parasternal was easily accessible in all patients. The interobserver reproducibility was good (intraclass correlation coefficient, 0.77 (95% CI, 0.53 to 0.89). There was a progressive decrease in parasternal muscle thickening fraction with increasing levels of pressure support (Spearman ρ = -0.61 [95% CI, -0.74 to -0.44]; P < 0.0001) and an inverse correlation between parasternal muscle thickening fraction and the pressure generating capacity of the diaphragm (Spearman ρ = -0.79 [95% CI, -0.87 to -0.66]; P < 0.0001). The parasternal muscle thickening fraction was higher in patients with diaphragm dysfunction: 17% (10 to 25) versus 5% (3 to 8), P < 0.0001. The pressure generating capacity of the diaphragm, the diaphragm thickening fraction and the parasternal thickening fraction similarly predicted failure or the spontaneous breathing trial., Conclusions: Ultrasound assessment of the parasternal intercostal muscle is feasible in the intensive care unit and provides novel information regarding the respiratory capacity load balance.

Background: Intensive care unit (ICU)-acquired weakness and diaphragm dysfunction are frequent conditions, both associated with poor prognosis in critically ill patients. While it is well established that ICU-acquired weakness severely impairs long-term prognosis, the association of diaphragm dysfunction with this outcome has never been reported. This study investigated whether diaphragm dysfunction is associated with negative long-term outcomes and whether the coexistence of diaphragm dysfunction and ICU-acquired weakness has a particular association with 2-year survival and health-related quality of life (HRQOL)., Methods: This study is an ancillary study derived from an observational cohort study. Patients under mechanical ventilation were enrolled at the time of their first spontaneous breathing trial. Diaphragm dysfunction was defined by tracheal pressure generated by phrenic nerve stimulation < 11 cmH 2 O and ICU-acquired weakness was defined by Medical Research Council (MRC) score < 48. HRQOL was evaluated with the SF-36 questionnaire., Results: Sixty-nine of the 76 patients enrolled in the original study were included in the survival analysis and 40 were interviewed. Overall 2-year survival was 67% (46/69): 64% (29/45) in patients with diaphragm dysfunction, 71% (17/24) in patients without diaphragm dysfunction, 46% (11/24) in patients with ICU-acquired weakness and 76% (34/45) in patients without ICU-acquired weakness. Patients with concomitant diaphragm dysfunction and ICU-acquired weakness had a poorer outcome with a 2-year survival rate of 36% (5/14) compared to patients without diaphragm function and ICU-acquired weakness [79% (11/14) (p < 0.01)]. Health-related quality of life was not influenced by the presence of ICU-acquired weakness, diaphragm dysfunction or their coexistence., Conclusions: ICU-acquired weakness but not diaphragm dysfunction was associated with a poor 2-year survival of critically ill patients.

Background: Intensive care unit (ICU)-acquired weakness (ICU-AW) and ICU-acquired diaphragm dysfunction (ICU-DD) occur frequently in mechanically ventilated (MV) patients. It is unknown whether they have different risk factors and different impacts on outcome. This study was designed to (1) describe the respective risk factors associated with ICU-AW and severe ICU-DD and (2) evaluate the respective impact of ICU-AW and severe ICU-DD on outcome., Methods: Post hoc analysis of two prospective cohort studies conducted in two ICUs. In patients mechanically ventilated for at least 24 h undergoing a first spontaneous breathing trial, severe ICU-DD was defined as diaphragm twitch pressure < 7 cmH 2 O and ICU-AW was defined as Medical Research Council Score < 48., Results: One hundred sixteen patients were assessed. Factors independently associated with severe ICU-DD were age, longer duration of MV, and exposure to sufentanil, and those factors associated with ICU-AW were longer duration of MV and exposure to norepinephrine. Severe ICU-DD (OR 3.56, p = 0.008), but not ICU-AW, was independently associated with weaning failure (59%). ICU-AW (OR 4.30, p = 0.033), but not severe ICU-DD, was associated with ICU mortality. Weaning failure and mortality rate were higher in patients with both severe ICU-DD and ICU-AW (86% and 39%, respectively) than in patients with either severe ICU-DD (64% and 0%) or ICU-AW (63% and 13%)., Conclusion: Severe ICU-DD and ICU-AW have different risk factors and different impacts on weaning failure and mortality. The impact of the combination of ICU-DD and ICU-AW is more pronounced than their individual impact.

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., Competing Interests: Conflict of interest: P. Laveneziana reports personal fees from Novartis France and Boehringer France, outside the submitted work. Conflict of interest: A. Albuquerque has nothing to disclose. Conflict of interest: A. Aliverti has a patent optoelectronic plethysmography licensed to BTS Bioengineering. Conflict of interest: T. Babb has nothing to disclose. Conflict of interest: E. Barreiro has nothing to disclose. Conflict of interest: M. Dres reports personal fees for research from Lungpacer, fees for conference accommodation from Pulsion Medical System and Maquet, outside the submitted work. Conflict of interest: B-P. Dubé reports grants and personal fees from Novartis and Roche, personal fees from Boehringer Ingelheim and GSK, outside the submitted work. Conflict of interest: B. Fauroux has nothing to disclose. Conflict of interest: J. Gea has nothing to disclose. Conflict of interest: J.A. Guenette has nothing to disclose. Conflict of interest: A.L. Hudson reports grants from Lung Foundation Australia and Boehringer Ingelheim, during the conduct of the study; grants from Rebecca L. Cooper Foundation, Lung Foundation Australia, Boehringer Ingelheim, National Health and Medical Research Council (Australia) and University of New South Wales, outside the submitted work. Conflict of interest: H-J. Kabitz reports personal fees and non-financial support from Inomed Medizintechnik GmbH, non-financial support from nSpire Health GmbH, during the conduct of the study. Conflict of interest: F. Laghi reports grants from National Institutes of Health, VA Research Service, Liberate Medical LLC and National Science Foundation, outside the submitted work. Conflict of interest: D. Langer has nothing to disclose. Conflict of interest: Y-M. Luo has nothing to disclose. Conflict of interest: J.A. Neder has nothing to disclose. Conflict of interest: D. O'Donnell reports grants and personal fees from AstraZeneca, Boehringer Ingelheim and GlaxoSmithKline, personal fees from Almirall, Novartis and Pfizer, outside the submitted work. Conflict of interest: M.I. Polkey reports personal and institutional payments for consultancy and speaking from Amicus, Genzyme Sanofi and Biomarin, institutional payments for consultancy from Orion, during the conduct of the study. Conflict of interest: R.A. Rabinovich has nothing to disclose. Conflict of interest: A. Rossi has nothing to disclose. Conflict of interest: F. Series has nothing to disclose. Conflict of interest: T. Similowski reports personal fees for advisory board work from Pierre Fabre Médicament, during the conduct of the study; personal fees from AstraZeneca, Boehringer Ingelheim France, GSK, Lungpacer Inc., TEVA, Chiesi and Invacare, personal fees and non-financial support from Novartis, outside the submitted work. Conflict of interest: C.M. Spengler has nothing to disclose. Conflict of interest: I. Vogiatzis has nothing to disclose. Conflict of interest: S. Verges has nothing to disclose., (Copyright ©ERS 2019.)

Characterizing the breathing pattern in naturally breathing humans brings important information on respiratory mechanics, respiratory muscle, and breathing control. However, measuring breathing modifies breathing (observer effect) through the effects of instrumentation and awareness: measuring human breathing under true ecological conditions is currently impossible. This study tested the hypothesis that non-contact vibrometry using airborne ultrasound (SONAR) could measure breathing movements in a contactless and invisible manner. Thus, first, we evaluated the validity of SONAR measurements by testing their interchangeability with pneumotachograph (PNT) measurements obtained at the same time. We also aimed at evaluating the observer effect by comparing breathing variability obtained by SONAR versus SONAR-PNT measurements. Twenty-three healthy subjects (12 men and 11 women; mean age 33 years - range: 20-54) were studied during resting breathing while sitting on a chair. Breathing activity was described in terms of ventilatory flow measured using a PNT and, either simultaneously or sequentially, with a SONAR device measuring the velocity of the surface motion of the chest wall. SONAR was focused either anteriorly on the xiphoid process or posteriorly on the lower part of the costal margin. Discrete ventilatory temporal and volume variables and their coefficients of variability were calculated from the flow signal (PNT) and the velocity signal (SONAR) and tested for interchangeability (Passing-Bablok regression). Tidal volume (VT) and displacement were linearly related. Breathing frequency (BF), total cycle time (TT), inspiratory time (TI), and expiratory time (TE) met interchangeability criteria. Their coefficients of variation were not statistically significantly different with PNT and SONAR-only. This was true for both the anterior and the posterior SONAR measurements. Non-contact vibrometry using airborne ultrasound is a valid tool for measuring resting breathing pattern.

Background: Although mainly described in patients with chronic obstructive pulmonary disease, pursed lip breathing (PLB) could prove useful in patients with interstitial lung disease (ILD) by improving exertional tachypnea and respiratory control. This prospective, randomized, crossover trial aimed at evaluating the impact of PLB on dyspnea and walking distance in ILD patients., Methods: ILD patients with total lung capacity of <80% predicted were randomized to 6-min walk tests using either PLB or usual breathing. Patients were crossed over for the second 6-min walk tests and served as their own controls. Ventilatory and metabolic variables were recorded using a portable metabolic cart and were compared at 1-min intervals., Results: Thirty-five patients were included (mean forced vital capacity of 64 ± 10% predicted). Use of PLB resulted in lower mean respiratory rates and larger tidal volumes (both P < .001), worsened dyspnea ratings (post-6-min walk test Borg score: 5.2 ± 2.6 vs 4.2 ± 2.3, P < .001), and walking distance (403 ± 102 m vs 429 ± 93 m, P < .001). Twenty-nine patients (83%) described PLB as less comfortable than usual breathing. Both groups had similar total ventilation and oxygen saturation (all P > .05), but PLB resulted in higher mean oxygen uptake (13.9 ± 3.6 vs 12.9 ± 3.2 mL/kg/min, P = .02), even when corrected for walking distance (P < .001)., Conclusion: In ILD patients, acute exposure to PLB did not improve exertional dyspnea, walking distance, or gas exchange, and was associated with higher metabolic demands than usual breathing. These results cast doubt on the usefulness of this technique in ILD patients and should be taken into account when tailoring pulmonary rehabilitation programs to this population.

Introduction: In methacholine challenge testing (MCT), skipping a methacholine dose is suggested if FEV 1  falls by < 5%. Using a larger threshold may further shorten test duration, but data supporting this hypothesis is lacking. We evaluated the safety and consequences of using a 10% FEV 1  fall as threshold to skip the next dose of methacholine in patients undergoing MCT., Methods: We reviewed MCTs performed in our center in 2017-2018. A ≤ 10% FEV 1  fall allowed the omission of the next methacholine dose. Patients of interest were those in which a dose was skipped after a previous FEV 1  fall outside the usual range (5-10%, termed "skip 5-10% "). Adverse events [AE; mild: > 1 nebulized salbutamol dose (2.5 mg) to reach basal FEV 1 , palpitations; severe: hypoxemia and/or need for medical attention or intervention] were compared in the skip 5-10%  group and others. Regression analysis was used to identify predictors of AE., Results: 208 MCTs were analysed (135 males, age 52 ± 15 years). Skip 5-10%  occurred 111 times in 90 tests. Prevalence of AE was 5% and all were mild. Patients who developed AEs had lower FEV 1 , FVC and FEV 1 /FVC ratio, and higher lung volume values (all p < 0.05), but similar prevalence of skip 5-10% (36 vs. 44%, p = 0.64). Overall, MCTs in which at least one skip 5-10% occurred had a lower mean number of doses (3.1 ± 0.6 vs. 3.5 ± 1.3 doses, p = 0.007). Baseline residual volume was independently related to the development of AEs (OR 1.05, 95% CI 1.01-1.10, p = 0.01), but not the presence of a skip 5-10% , even when the skipped dose directly led to the reaching of PC 20 (OR 5.40, 95% CI 0.73-39.22, p = 0.10)., Conclusion: Omitting a methacholine dose based on a ≤ 10% fall in FEV 1  occurs frequently and has the potential to shorten test duration. AE are rare, but patients with worse baseline lung function and gas trapping are at increased risk of mild side effects.

Case Presentation: A 63-year-old man was referred for slowly progressive dyspnea on exertion that had developed over 7 years. Dyspnea was initially only present during high-intensity physical activity, but was now present while walking rapidly on a flat surface. Symptoms were accentuated while supine and when bending forward. He reported respiratory difficulties when submerged in water and a recent onset of slight symmetric lower limb weakness that was only apparent during strenuous physical activity. He also had OSA, which was adequately controlled with continuous positive airway pressure therapy. Neurologic and rheumatologic histories were otherwise unremarkable. He denied any impact accidents or trauma to the cervical spine and prior neck or thoracic surgeries., (Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Chronic obstructive pulmonary disease (COPD) is a prevalent, complex and debilitating disease which imposes a formidable burden on patients and the healthcare system. The recognition that COPD is a multifaceted disease is not new, and increasing evidence have outlined the importance of its extra-pulmonary manifestations and its relation to other comorbid conditions in the clinical course of the disease and its societal cost. The relationship between aging, COPD and its comorbidities on skeletal muscle function and nutritional status is complex, multidirectional and incompletely understood. Despite this, the current body of knowledge allows the identification of various, seemingly partially independent factors related both to the normal aging process and to the independent deleterious effects of chronic diseases on muscle function and body composition. There is a dire need of studies evaluating the relative contribution of each of these factors, and their potential synergistic effects in patients with COPD and advanced age/comorbid conditions, in order to delineate the best course of therapeutic action in this increasingly prevalent population., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background: Diaphragm dysfunction is defined by a value of twitch tracheal pressure in response to magnetic phrenic stimulation (twitch pressure) amounting to less than 11 cmH 2 O. This study assessed whether this threshold or a lower one would predict accurately weaning failure from mechanical ventilation. Twitch pressure was compared to ultrasound measurement of diaphragm function., Methods: In patients undergoing a first spontaneous breathing trial, diaphragm function was evaluated by twitch pressure and by diaphragm ultrasound (thickening fraction). Receiver operating characteristics curves were computed to determine the best thresholds predicting failure of spontaneous breathing trial., Results: Seventy-six patients were evaluated, 48 (63%) succeeded and 28 (37%) failed the spontaneous breathing trial. The optimal thresholds of twitch pressure and thickening fraction to predict failure of the spontaneous breathing trial were, respectively, 7.2 cmH 2 O and 25.8%, respectively. The receiver operating characteristics curves were 0.80 (95% CI 0.70-0.89) for twitch pressure and 0.82 (95% CI 0.73-0.93) for thickening fraction. Both receiver operating characteristics curves were similar (p = 0.83). A twitch pressure value lower than 11 cmH 2 O (the traditional cutoff for diaphragm dysfunction) predicted failure of the spontaneous breathing trial with a sensitivity of 89% (95% CI 72-98%) and a specificity of 45% (95% CI 30-60%)., Conclusions: Failure of spontaneous breathing trial can be predicted with a lower value of twitch pressure than the value defining diaphragm dysfunction. Twitch pressure and thickening fraction had similar strong performance in the prediction of failure of the spontaneous breathing trial.

Rationale: In intensive care unit (ICU) patients, diaphragm dysfunction is associated with adverse clinical outcomes. Ultrasound measurements of diaphragm thickness, excursion (EXdi) and thickening fraction (TFdi) are putative estimators of diaphragm function, but have never been compared with phrenic nerve stimulation. Our aim was to describe the relationship between these variables and diaphragm function evaluated using the change in endotracheal pressure after phrenic nerve stimulation (Ptr,stim), and to compare their prognostic value., Methods: Between November 2014 and June 2015, Ptr,stim and ultrasound variables were measured in mechanically ventilated patients <24 hours after intubation ('initiation of mechanical ventilation (MV)', under assist-control ventilation, ACV) and at the time of switch to pressure support ventilation ('switch to PSV'), and compared using Spearman's correlation and receiver operating characteristic curve analysis. Diaphragm dysfunction was defined as Ptr,stim <11 cm H 2 O., Results: 112 patients were included. At initiation of MV, Ptr,stim was not correlated to diaphragm thickness (p=0.28), EXdi (p=0.66) or TFdi (p=0.80). At switch to PSV, TFdi and EXdi were respectively very strongly and moderately correlated to Ptr,stim, (r=0.87, p<0.001 and 0.45, p=0.001), but diaphragm thickness was not (p=0.45). A TFdi <29% could reliably identify diaphragm dysfunction (sensitivity and specificity of 85% and 88%), but diaphragm thickness and EXdi could not. This value was associated with increased duration of ICU stay and MV, and mortality., Conclusions: Under ACV, diaphragm thickness, EXdi and TFdi were uncorrelated to Ptr,stim. Under PSV, TFdi was strongly correlated to diaphragm strength and both were predictors of remaining length of MV and ICU and hospital death., Competing Interests: Competing interests: B-PD has received honoraria from GlaxoSmithKline, Boehringer Ingelheim, Astra Zeneca and Roche. AD has signed research contracts with Covidien, Maquet and Philips; he has also received personal fees from Covidien and MSD. MD received personal fees from Pulsion Medical System and Astra Zeneca. Relevant to the present study, TS has received personal fees from Lungpacer and is a member of the board of a research association that has received, over the past 10 years, unrestricted research grants from Maquet, Hamilton, Covidien and Philips; he is the head of a research unit (UMRS 1158) that has signed research contracts with Air Liquide Medical Systems, France; he is listed as inventor or co-inventor on several patents, granted or pending, describing a brain-ventilator interface., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

The use of a mouthpiece to measure ventilatory flow with a pneumotachograph (PNT) introduces a major perturbation to breathing ("instrumental/observer effect") and suffices to modify the respiratory behavior. Structured light plethysmography (SLP) is a non-contact method of assessment of breathing pattern during tidal breathing. Firstly, we validated the SLP measurements by comparing timing components of the ventilatory pattern obtained by SLP vs. PNT under the same condition; secondly, we compared SLP to SLP+PNT measurements of breathing pattern to evaluate the disruption of breathing pattern and breathing variability in healthy and COPD subjects. Measurements were taken during tidal breathing with SLP alone and SLP+PNT recording in 30 COPD and healthy subjects. Measurements included: respiratory frequency (R f ), inspiratory, expiratory, and total breath time/duration (Ti, Te, and Tt). Passing-Bablok regression analysis was used to evaluate the interchangeability of timing components of the ventilatory pattern (R f , Ti, Te, and Tt) between measurements performed under the following experimental conditions: SLP vs. PNT, SLP+PNT vs. SLP, and SLP+PNT vs. PNT. The variability of different ventilatory variables was assessed through their coefficients of variation (CVs). In healthy: according to Passing-Bablok regression, Rf, TI, TE and TT were interchangeable between measurements obtained under the three experimental conditions (SLP vs. PNT, SLP+PNT vs. SLP, and SLP+PNT vs. PNT). All the CVs describing "traditional" ventilatory variables (R f , Ti, Te, Ti/Te, and Ti/Tt) were significantly smaller in SLP+PNT condition. This was not the case for more "specific" SLP-derived variables. In COPD: according to Passing-Bablok regression, Rf, TI, TE, and TT were interchangeable between measurements obtained under SLP vs. PNT and SLP+PNT vs. PNT, whereas only Rf, TE, and TT were interchangeable between measurements obtained under SLP+PNT vs. SLP. However, most discrete variables were significantly different between the SLP and SLP+PNT conditions and CVs were significantly lower when COPD patients were assessed in the SLP+PNT condition. Measuring ventilatory activity with SLP preserves resting tidal breathing variability, reduces instrumental observer effect and avoids any disruptions in breathing pattern induced by the use of PNT-mouthpiece-nose-clip combination.

Introduction: The beneficial impact of an 8-month competitive season on the ventilatory profile response to exercise in soccer players has never been evaluated., Material and Methods: Ventilatory profile (evaluated by determining individual tidal volume [V T ] relative to minute ventilation [V E ] inflection points during exercise) and metabolic responses to incremental exercise were evaluated in 2 professional soccer teams before and after an 8-month competitive season., Results: No differences between teams in anthropometric characteristics or in resting cardiopulmonary variables, included oxygen uptake (VO 2 ) and heart rate (HR), before and during the competitive season were found. At iso-speed, there were overall improvements in carbon dioxide output (VCO 2 ), V E /VO 2 , V E /VCO 2 , V E and respiratory frequency (fR) during the season. The V T /V E inflection points 1 and 2 occurred with greater exercise time, HR, VO 2 , VCO 2 , V E and V T during the competitive season., Conclusions: Despite very high baseline performance and a negligible improvement in VO 2 , an 8-month competitive season improved ventilatory profile response to exercise in elite athletes., (Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)

Purpose: The aim of this study was to explore the potential and safety of a stair-climbing test as a tool to monitor improvement following pulmonary rehabilitation (PR) in patients with chronic obstructive pulmonary disease (COPD)., Methods: Stair-climbing capacity was assessed in 139 patients with COPD before and after a comprehensive 8-week PR program, which included stair-climbing training. Stair-climbing capacity was assessed as the total number of flights of stairs climbed without stopping. A constant work rate endurance test (CET) was also performed before and after PR. Change in stair-climbing after PR (Δstairs) was compared and correlated to the change in endurance time (ΔCET) and, for 40 patients, to the change in COPD assessment test (ΔCAT) score., Results: Most patients had moderate to severe COPD (mean forced expiratory volume in 1 second = 54% ± 20% predicted). Stair-climbing capacity, endurance time, and CAT score improved after PR (2.8 ± 1.4 vs 8.3 ± 3.3 flights, 408 ± 272 vs 717 ± 415 seconds, and 20.0 ± 6.4 vs 17.6 ± 6.6 units, respectively; P value for all < .001). Δstairs was moderately correlated to ΔCET (r = 0.49; P < .001) and well correlated to ΔCAT (r = -0.71; P < .001). Patients with greater change in Δstairs had better baseline resting lung function and aerobic capacity. No adverse events were reported during stair-climbing., Conclusion: Stair-climbing is responsive to training in patients with COPD and is correlated to the change in CAT score following PR. Although the test requires further standardization, it could eventually be used as a simple and safe way to assess improvement following interventions in COPD.

Background: The treatment of chronic hypersensitivity pneumonitis (cHP) often includes systemic oral corticosteroids, but the optimal pharmacologic management remains unclear. The morbidity associated with prednisone has motivated the search for alternative therapies. We aimed to determine the effect of treatment with mycophenolate mofetil (MMF) or azathioprine (AZA) on lung function in patients with cHP., Methods: Patients with cHP treated with either MMF or AZA were retrospectively identified from four interstitial lung disease centers. Change in lung function before and after treatment initiation was analyzed using linear mixed-effects modeling (LMM), adjusting for age, sex, smoking history, and prednisone use., Results: Seventy patients were included: 51 were treated with MMF and 19 with AZA. Median follow-up after treatment initiation was 11 months. Prior to treatment initiation, FVC and diffusion capacity of the lung for carbon monoxide (Dlco) % predicted were declining at a mean rate of 0.12% (P < .001) and 0.10% (P < .001) per month, respectively. Treatment with either MMF or AZA was not associated with improved FVC (0.5% at 1 year; P = .46) but was associated with a statistically significant improvement in Dlco of 4.2% (P < .001) after 1 year of treatment. Results were similar in the subgroup of patients treated with MMF for 1 year; the FVC increased nonsignificantly by 1.3% (P = .103) and Dlco increased by 3.9% (P < .001)., Conclusions: Treatment with MMF or AZA is associated with improvements in Dlco in patients with cHP. Prospective randomized trials are needed to validate their effectiveness for cHP., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Dyspnoea is a complex, highly personalized and multidimensional sensory experience, and its underlying cause and mechanisms are still being investigated. Exertional dyspnoea is one of the most frequently encountered symptoms of patients with cardiopulmonary diseases, and is a common reason for seeking medical help. As the symptom usually progresses with the underlying disease, it can lead to an avoidance of physical activity, peripheral muscle deconditioning and decreased quality of life. Dyspnoea is closely associated with quality of life, exercise (in)tolerance and prognosis in various conditions, including chronic obstructive pulmonary disease, heart failure, interstitial lung disease and pulmonary hypertension, and is therefore an important therapeutic target. Effective management and treatment of dyspnoea is an important challenge for caregivers, and therapeutic options that attempt to reverse its underlying cause have been only partially successful This "review" will attempt to shed light on the physiological mechanisms underlying dyspnoea during exercise and to translate/apply them to a broad clinical spectrum of cardio-respiratory disorders., (Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)

Rationale: Intensive care unit (ICU)- and mechanical ventilation (MV)-acquired limb muscle and diaphragm dysfunction may both be associated with longer length of stay and worse outcome. Whether they are two aspects of the same entity or have a different prevalence and prognostic impact remains unclear., Objectives: To quantify the prevalence and coexistence of these two forms of ICU-acquired weakness and their impact on outcome., Methods: In patients undergoing a first spontaneous breathing trial after at least 24 hours of MV, diaphragm dysfunction was evaluated using twitch tracheal pressure in response to bilateral anterior magnetic phrenic nerve stimulation (a pressure <11 cm H 2 O defined dysfunction) and ultrasonography (thickening fraction [TFdi] and excursion). Limb muscle weakness was defined as a Medical Research Council (MRC) score less than 48., Measurements and Main Results: Seventy-six patients were assessed at their first spontaneous breathing trial: 63% had diaphragm dysfunction, 34% had limb muscle weakness, and 21% had both. There was a significant but weak correlation between MRC score and twitch pressure (ρ = 0.26; P = 0.03) and TFdi (ρ = 0.28; P = 0.01), respectively. Low twitch pressure (odds ratio, 0.60; 95% confidence interval, 0.45-0.79; P < 0.001) and TFdi (odds ratio, 0.84; 95% confidence interval, 0.76-0.92; P < 0.001) were independently associated with weaning failure, but the MRC score was not. Diaphragm dysfunction was associated with higher ICU and hospital mortality, and limb muscle weakness was associated with longer duration of MV and hospital stay., Conclusions: Diaphragm dysfunction is twice as frequent as limb muscle weakness and has a direct negative impact on weaning outcome. The two types of muscle weakness have only limited overlap.

The diaphragm is the main inspiratory muscle, and its dysfunction can lead to significant adverse clinical consequences. The aim of this review is to provide clinicians with an overview of the main causes of uni- and bi-lateral diaphragm dysfunction, explore the clinical and physiological consequences of the disease on lung function, exercise physiology and sleep and review the available diagnostic tools used in the evaluation of diaphragm function. A particular emphasis is placed on the clinical significance of diaphragm weakness in the intensive care unit setting and the use of ultrasound to evaluate diaphragmatic action., Competing Interests: The authors declare no conflict of interest.

Exertional dyspnoea is among the dominant symptoms in patients with chronic heart failure and progresses relentlessly as the disease advances, leading to reduced ability to function and engage in activities of daily living. Effective management of this disabling symptom awaits a better understanding of its underlying physiology.Cardiovascular factors are believed to play a major role in dyspnoea in heart failure patients. However, despite pharmacological interventions, such as vasodilators or inotropes that improve central haemodynamics, patients with heart failure still complain of exertional dyspnoea. Clearly, dyspnoea is not determined by cardiac factors alone, but likely depends on complex, integrated cardio-pulmonary interactions.A growing body of evidence suggests that excessively increased ventilatory demand and abnormal "restrictive" constraints on tidal volume expansion with development of critical mechanical limitation of ventilation, contribute to exertional dyspnoea in heart failure. This article will offer new insights into the pathophysiological mechanisms of exertional dyspnoea in patients with chronic heart failure by exploring the potential role of the various constituents of the physiological response to exercise and particularly the role of abnormal ventilatory and respiratory mechanics responses to exercise in the perception of dyspnoea in patients with heart failure., (Copyright ©ERS 2016.)

Rationale: There is no standardized education program for patients with interstitial lung disease (ILD). Pulmonary rehabilitation is a resource for structured disease education that is still geared primarily toward patients with chronic obstructive pulmonary disease., Objectives: The goals of this qualitative study were to identify the educational needs of patients with ILD and explore how pulmonary rehabilitation can become an appropriate setting for ILD education., Methods: Four focus groups including 24 patients with ILD and 10 semistructured interviews with healthcare professionals with expertise in ILD and/or pulmonary rehabilitation were conducted in two academic centers (University of California San Francisco and Centre Hospitalier de l'Université de Montréal). We conducted a qualitative thematic analysis of the transcripts using an iteratively developed codebook., Measurements and Main Results: The transcript analysis highlighted four major themes: patient dissatisfaction with the current educational model, lack of attention to emotional well-being, specific recommendations for educational content, and operationalizing education in the context of pulmonary rehabilitation. Seven key topics to be included an ILD-specific, pulmonary rehabilitation-based education program were identified: disease education, symptom management, clinical tests, autonomy, oxygen use, medications, and end-of-life counseling., Conclusions: This study provides a better understanding of the needs of patients and healthcare providers regarding education of patients with ILD. It lays the foundation for the development of a structured education intervention that could be delivered in the context of pulmonary rehabilitation.

Purpose: The purpose of this study was to determine the interobserver reliability of the assessment of the ventilatory threshold (VT) using two methods in patients with chronic obstructive pulmonary disease (COPD) and in control subjects., Methods: VT was identified from incremental exercise testing graphs of 115 subjects (23 controls and 23 in each COPD Global initiative for chronic Obstructive Lung Disease class) by two human observers and a computer analysis using the V-slope method and the ventilatory equivalent method (VEM). Agreement between observers in identifying oxygen uptake at VT (VO 2VT) and HR at VT (HR VT) across disease severity groups was evaluated using intraclass correlation (for humans) and Passing-Bablok regression analysis (human vs computer)., Results: For human observers, ICC (95% confidence interval) in determining VO 2VT were higher in controls (0.98 (0.97-0.99) both with V-slope and with VEM) than those in COPD patients (0.72 (0.60-0.81) with V-slope and 0.64 (0.50-0.74) with VEM). Passing-Bablok analysis showed that human and computerized determination of VO 2VT was interchangeable in controls but not in patients with COPD. Forced expiratory volume in one second and peak minute ventilation during exercise were the only variables independently associated with greater interobserver differences in VO 2VT. Interobserver differences in HRVT ranged from 2 ± 1 (controls) to 10 ± 3 bpm (GOLD 4)., Conclusions: In patients with COPD, the reliability of human estimation of VO 2VT is less than that in controls and not interchangeable with a computerized analysis. This should be taken into account when using VT for exercise prescription, as a tool to monitor responses to an intervention, as a surrogate measure of overall aerobic fitness, or as a prognostic marker in patients with COPD.