Myositis with prominent B-cell aggregates causing shrinking lung syndrome in systemic lupus erythematosus: a case report.

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.

Predictive value of positional change in vital capacity to identify diaphragm dysfunction.

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.

Determinants and functional impacts of diaphragmatic involvement in patients with inclusion body myositis.

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.

Ultrasound-Derived Diaphragm Contractile Reserve as a Marker of Clinical Status in Patients With Cystic Fibrosis.

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 (FEV1), 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, FEV1 66 (46-82)% predicted]. DCR was significantly correlated to FEV1 (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 FEV1 (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.

Central neurogenic hyperventilation in conscious patients due to CNS neoplasm: a case report and review of the literature on treatment.

BACKGROUND: Central neurogenic hyperventilation (CNH) is increasingly reported in conscious patients with a CNS neoplasm. We aimed to synthesize the available data on the treatment of this condition to guide clinicians in their approach. METHODS: We describe the case of a 39-year-old conscious woman with CNH secondary to glioma brainstem infiltration for whom hyperventilation was aborted with hydromorphone, dexamethasone, and brainstem radiotherapy. We then performed a review of the literature on the treatment of CNH in conscious patients due to a CNS neoplasm. RESULTS: A total of 31 studies reporting 33 cases fulfilled the selection criteria. The underlying neoplasm was lymphoma in 15 (45%) and glioma in 13 (39%) patients. Overall, CNH was aborted in 70% of cases. Opioids and sedatives overall seemed useful for symptom relief, but the benefit was often of short duration when the medication was administered orally or subcutaneously. Methadone and fentanyl were successful but rarely used. Chemotherapy was most effective in patients with lymphoma (89%), but not glioma (0%) or other neoplasms (0%). Patients with lymphoma (80%) and other tumors (100%) responded to radiotherapy more frequently than patients with glioma (43%). Corticosteroids were moderately effective. Subtotal surgical resection was successful in the 3 cases for which it was attempted. CONCLUSION: Definitive treatment of the underlying neoplasm may be more successful in aborting hyperventilation. Variable rates of palliation have been observed with opioids and sedatives. Treatment of CNH is challenging but successful in a majority of cases.

Ultrasound Evaluation of the Quadriceps Muscle Contractile Index in Patients with Stable Chronic Obstructive Pulmonary Disease: Relationships with Clinical Symptoms, Disease Severity and Diaphragm Contractility.

Rationale: 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.

Usefulness of Parasternal Intercostal Muscle Ultrasound during Weaning from Mechanical Ventilation.

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.

ICU-acquired weakness, diaphragm dysfunction and long-term outcomes of critically ill patients.

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 cmH2O 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.

Respective contribution of intensive care unit-acquired limb muscle and severe diaphragm weakness on weaning outcome and mortality: a post hoc analysis of two cohorts.

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 cmH2O 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.

Physiological Validation of an Airborne Ultrasound Based Surface Motion Camera for a Contactless Characterization of Breathing Pattern in Humans.

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.

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.

Effects of Pursed Lip Breathing on Exercise Capacity and Dyspnea in Patients With Interstitial Lung Disease: A RANDOMIZED, CROSSOVER STUDY.

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.

Dose omission to shorten methacholine challenge testing: clinical consequences of the use of a 10% fall in FEV1 threshold.

INTRODUCTION: In methacholine challenge testing (MCT), skipping a methacholine dose is suggested if FEV1 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% FEV1 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% FEV1 fall allowed the omission of the next methacholine dose. Patients of interest were those in which a dose was skipped after a previous FEV1 fall outside the usual range (5-10%, termed "skip5-10%"). Adverse events [AE; mild: > 1 nebulized salbutamol dose (2.5 mg) to reach basal FEV1, palpitations; severe: hypoxemia and/or need for medical attention or intervention] were compared in the skip5-10% group and others. Regression analysis was used to identify predictors of AE. RESULTS: 208 MCTs were analysed (135 males, age 52 ± 15 years). Skip5-10% occurred 111 times in 90 tests. Prevalence of AE was 5% and all were mild. Patients who developed AEs had lower FEV1, FVC and FEV1/FVC ratio, and higher lung volume values (all p < 0.05), but similar prevalence of skip5-10% (36 vs. 44%, p = 0.64). Overall, MCTs in which at least one skip5-10% 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 skip5-10%, even when the skipped dose directly led to the reaching of PC20 (OR 5.40, 95% CI 0.73-39.22, p = 0.10). CONCLUSION: Omitting a methacholine dose based on a ≤ 10% fall in FEV1 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.

A 63-Year-Old Man Presents With Slowly Progressive Dyspnea on Exertion and Lower Extremity Muscle Weakness.

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.

Effects of aging and comorbidities on nutritional status and muscle dysfunction in patients with COPD.

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.

Diaphragm function and weaning from mechanical ventilation: an ultrasound and phrenic nerve stimulation clinical study.

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 cmH2O. 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 cmH2O 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 cmH2O (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.

Measuring Ventilatory Activity with Structured Light Plethysmography (SLP) Reduces Instrumental Observer Effect and Preserves Tidal Breathing Variability in Healthy and COPD.

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 (Rf), 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 (Rf, 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 (Rf, 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.

Cambios en la respuesta ventilatoria al esfuerzo en deportistas entrenados: efectos beneficiosos sobre la fisiología respiratoria más allá del rendimiento cardiovascular / Changes in Ventilatory Response to Exercise in Trained Athletes: Respiratory Physiological Benefits Beyond Cardiovascular Performance

Introducción: El efecto beneficioso de una temporada de competición de 8meses sobre el perfil ventilatorio en respuesta al esfuerzo no se ha evaluado en jugadores de fútbol. Material y métodos: Se evaluó el perfil ventilatorio (analizando los puntos de inflexión específicos del cociente entre el volumen corriente [VT] y la ventilación [VE] durante el esfuerzo) y la respuesta metabólica al esfuerzo gradual en 2 equipos de fútbol profesional, antes y después de una temporada de competición de 8 meses. Resultados: No se observaron diferencias entre equipos en las características antropométricas ni en las variables cardiopulmonares en reposo, incluidos el consumo de oxígeno (VO2) y la frecuencia cardíaca (FC). Durante la temporada de competición, a velocidad fija, se observaron mejorías globales en la producción de dióxido de carbono (VCO2), los cocientes VE/VO2 y VE/VCO2, la VE y la frecuencia respiratoria (FR). Los puntos de inflexión 1 y 2 del cociente VT/VE se observaron tras un mayor tiempo de ejercicio y mayores FC, VO2, VCO2, VE y VT durante la temporada de competición. Conclusiones: A pesar del elevado rendimiento inicial y de la escasa mejoría del VO2, la temporada de competición de 8 meses mejoró el perfil ventilatorio en respuesta al esfuerzo de estos deportistas de élite

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 [VT] relative to minute ventilation [VE] 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 (VO2) and heart rate (HR), before and during the competitive season were found. At iso-speed, there were overall improvements in carbon dioxide output (VCO2), VE/VO2, VE/VCO2, VE and respiratory frequency (fR) during the season. The VT/VE inflection points 1 and 2 occurred with greater exercise time, HR, VO2, VCO2, VE and VT during the competitive season. Conclusions: Despite very high baseline performance and a negligible improvement in VO2, an 8-month competitive season improved ventilatory profile response to exercise in elite athletes

Ultrasound evaluation of diaphragm function in mechanically ventilated patients: comparison to phrenic stimulation and prognostic implications.

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 H2O. 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.

Changes in Ventilatory Response to Exercise in Trained Athletes: Respiratory Physiological Benefits Beyond Cardiovascular Performance. / Cambios en la respuesta ventilatoria al esfuerzo en deportistas entrenados: efectos beneficiosos sobre la fisiología respiratoria más allá del rendimiento cardiovascular.

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 [VT] relative to minute ventilation [VE] 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 (VO2) and heart rate (HR), before and during the competitive season were found. At iso-speed, there were overall improvements in carbon dioxide output (VCO2), VE/VO2, VE/VCO2, VE and respiratory frequency (fR) during the season. The VT/VE inflection points 1 and 2 occurred with greater exercise time, HR, VO2, VCO2, VE and VT during the competitive season. CONCLUSIONS: Despite very high baseline performance and a negligible improvement in VO2, an 8-month competitive season improved ventilatory profile response to exercise in elite athletes.