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.

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.

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.

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.

Coexistence and Impact of Limb Muscle and Diaphragm Weakness at Time of Liberation from Mechanical Ventilation in Medical Intensive Care Unit Patients.

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 H2O 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.

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.

Porcine model of intracoronary pulverization of stent struts by rotablation atherectomy.

OBJECTIVE: To evaluate the feasibility and safety of rotablation atherectomy in a suboptimally expanded stent. METHODS: Seven pigs underwent suboptimal stent expansion in the left anterior descending coronary. Pulverization of the stent struts was performed by rotablation atherectomy with two different burr sizes. Two types of control porcine models were used: pigs with fully expanded stents and pigs without stents. Continuous electrocardiogram readings as well as microscopic and radiologic analysis of cardiac tissue were performed. RESULTS: Rotablation atherectomy reduces the suboptimally expanded stent by (26.95 ± 5.03)%. Ninety-five percent of the metal microparticles, imbedded in the suboptimally expanded stent group cardiac tissue, are less than 15 µm. Transient vasospasm and ST segments elevations were observed during rotablation atherectomy, which returned to basal conditions at the end of the intervention. CONCLUSION: Our study demonstrated the feasibility and safety of using rotablation atherectomy to pulverize stent struts in a suboptimally expanded stent.

Assessment of the sensitivity of detecting drug-induced QTc changes using subject-specific rate correction.

AIMS: To quantify the sensitivity of QT heart-rate correction methods for detecting drug-induced QTc changes in thorough QT studies. METHODS: Twenty-four-hour Holter ECGs were analyzed in 66 normal subjects during placebo and moxifloxacin delivery (single oral dose). QT and RR time series were extracted. Three QTc computation methods were used: (1) Fridericia's formula, (2) Fridericia's formula with hysteresis reduction, and (3) a subject-specific approach with transfer function-based hysteresis reduction and three-parameter non-linear fitting of the QT-RR relation. QTc distributions after placebo and moxifloxacin delivery were compared in sliding time windows using receiver operating characteristic (ROC) curves. The area under the ROC curve (AUC) served as a measure to quantify the ability of each method to detect moxifloxacin-induced QTc prolongation. RESULTS: Moxifloxacin prolonged the QTc by 10.6 ± 6.6 ms at peak effect. The AUC was significantly larger after hysteresis reduction (0.87 ± 0.13 vs. 0.82 ± 0.12, p<0.01) at peak effect, indicating a better discriminating capability. Subject-specific correction further increased the AUC to 0.91 ± 0.11 (p<0.01 vs. Fridericia with hysteresis reduction). The performance of the subject-specific approach was the consequence of a substantially lower intra-subject QTc standard deviation (5.7 ± 1.1 ms vs. 8.8 ± 1.2 ms for Fridericia). CONCLUSION: The ROC curve provides a tool for quantitative comparison of QT heart rate correction methods in the context of detecting drug-induced QTc prolongation. Results support a broader use of subject-specific QT correction.

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.

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.

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.

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.

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.

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.

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.

Attenuation of autonomic nervous system functions in hypertensive patients at rest and during orthostatic stimulation.

The effect of age on autonomic nervous system was assessed at rest and while standing using systolic blood pressure (SBP) and diastolic blood pressure (DBP), heart rate, and power spectral analysis of the time duration between 2 consecutive R waves of an electrocardiogram (RR) interval variability, as well as on plasma norepinephrine and epinephrine levels in mild to moderate hypertensive patients (DBP, 90-110 mm Hg). Patients younger than 60 years (n=57) and older than 60 years (n=32), were evaluated after a 3- to 4-week placebo period. Plasma catecholamines were measured in the supine position at rest and after 10 minutes of standing. Power spectral analysis of the RR interval variability was performed in each condition using the high-frequency (HF) band (0.15-0.4 Hz) as an index of parasympathetic activity and the low-frequency (LF) band (0.05-0.15 Hz) and LF-HF ratio to estimate sympathetic activity. The total power was calculated as the sum of LF and HF power. supine SBP was significantly higher in older patients (P<.05). SBP and DBP increased significantly only in younger patients during standing (P<.05), while the changes were smaller and nonsignificantly lower in older patients. HR was similar in both groups at rest and increased similarly during standing. Norepinephrine and epinephrine levels were similar at rest and increased similarly in both groups of patients during standing. At rest, lower LF and HF components were observed in older patients. The LF component increased less and the HF component decreased less in older patients during standing. A lower sympathetic and parasympathetic basal cardiac tone was observed at rest in older hypertensive patients. Moreover, reduced hemodynamic and sympathetic responses to standing as assessed by SBP, DBP, and the LF component of HR variability were observed in older hypertensives in the presence of a normal catecholamine response. These observations could reflect a decreased sensitivity of cardiac beta-adrenoceptors with aging.

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.

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.

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.