AVAPS-AE versus ST mode: A randomized controlled trial in patients with obesity hypoventilation syndrome.

BACKGROUND AND OBJECTIVE: Average volume-assured pressure support-automated expiratory positive airway pressure (AVAPS-AE) combines an automated positive expiratory pressure to maintain upper airway patency to an automated pressure support with a targeted tidal volume. The aim of this study was to compare the effects of 2-month AVAPS-AE ventilation versus pressure support (ST) ventilation on objective sleep quality in stable patients with OHS. Secondary outcomes included arterial blood gases, health-related quality of life, daytime sleepiness, subjective sleep quality and compliance to NIV. METHODS: This is a prospective multicentric randomized controlled trial. Consecutive OHS patients included had daytime Pa CO2 > 6 kPa, BMI ≥ 30 kg/m2 , clinical stability for more than 2 weeks and were naive from home NIV. PSG were analysed centrally by two independent experts. Primary endpoint was sleep quality improvement at 2 months. RESULTS: Among 69 trial patients, 60 patients had successful NIV setup. Baseline and follow-up PSG were available for 26 patients randomized in the ST group and 30 in the AVAPS-AE group. At baseline, Pa CO2 was 6.94 ± 0.71 kPa in the ST group and 6.61 ± 0.71 in the AVAPS-AE group (P = 0.032). No significant between-group difference was observed for objective sleep quality indices. Improvement in Pa CO2 was similar between groups with a mean reduction of -0.87 kPa (95% CI: -1.12 to -0.46) in the ST group versus -0.87 kPa (95% CI: -1.14 to -0.50) in the AVAPS-AE group (P = 0.984). Mean NIV use was 6.2 h per night in both groups (P = 0.93). NIV setup duration was shorter in the AVAPS-AE group (P = 0.012). CONCLUSION: AVAPS-AE and ST ventilation for 2 months had similar impact on sleep quality and gas exchange.

Measurement of thoraco-abdominal synchrony using respiratory inductance plethysmography: technical aspects and a proposal to overcome its limitations.

BACKGROUND: Thoraco-abdominal asynchrony (TAA) is usually assessed by respiratory inductance plethysmography. The main parameter used for its assessment is the calculation of the phase angle based on Lissajous plots. However, there are some mathematical limitations to its use. RESEARCH DESIGN AND METHODS: Sequences of five breaths were selected from a) normal subjects, b) COPD patients, both at rest and during exercise, and c) patients with obstructive apnea syndrome. Automated analysis was performed calculating phase angle, loop rotation (clockwise or counterclockwise), global phase delay and loop area. TAA severity was estimated quantitatively and in subgroups. RESULTS: 2290 cycles were analyzed (55% clockwise rotation). Phase angle ranged from -86.90 to + 88.4 degrees, while global phase delay ranged from -179.75 to + 178.54. Despite a good correlation with global phase delay (p < 0.01, ANOVA test), phase angle and loop area were not able to correctly classify breaths with severe deviation and paradoxical movements (p=ns, Bonferroni post hoc test). CONCLUSIONS: Global phase delay covers the whole spectrum of TAA situations in a single value. It may be a relevant parameter for diagnosis and follow-up of clinical conditions leading to TAA. CLINICAL TRIAL REGISTRATION: The trial from which the traces were obtained was registered at ClinicalTrials.gov ;(identifier: NCT04597606).

Abatacept/Ruxolitinib and Screening for Concomitant Respiratory Muscle Failure to Mitigate Fatality of Immune-Checkpoint Inhibitor Myocarditis.

Immune-checkpoint-inhibitor (ICI)-associated myotoxicity involves the heart (myocarditis) and skeletal muscles (myositis), which frequently occur concurrently and are highly fatal. We report the results of a strategy that included identification of individuals with severe ICI myocarditis by also screening for and managing concomitant respiratory muscle involvement with mechanical ventilation, as well as treatment with the CTLA4 fusion protein abatacept and the JAK inhibitor ruxolitinib. Forty cases with definite ICI myocarditis were included with pathologic confirmation of concomitant myositis in the majority of patients. In the first 10 patients, using recommended guidelines, myotoxicity-related fatality occurred in 60%, consistent with historical controls. In the subsequent 30 cases, we instituted systematic screening for respiratory muscle involvement coupled with active ventilation and treatment using ruxolitinib and abatacept. The abatacept dose was adjusted using CD86 receptor occupancy on circulating monocytes. The myotoxicity-related fatality rate was 3.4% (1/30) in these 30 patients versus 60% in the first quartile (P < 0.0001). These clinical results are hypothesis-generating and need further evaluation. SIGNIFICANCE: Early management of respiratory muscle failure using mechanical ventilation and high-dose abatacept with CD86 receptor occupancy monitoring combined with ruxolitinib may be promising to mitigate high fatality rates in severe ICI myocarditis. See related commentary by Dougan, p. 1040. This article is highlighted in the In This Issue feature, p. 1027.

Survival of amyotrophic lateral sclerosis patients after admission to the intensive care unit for acute respiratory failure: an observational cohort study.

PURPOSE: Amyotrophic lateral sclerosis (ALS) entails a risk of acute respiratory failure (ARF). The decision to admit such patients to the intensive care unit (ICU) is difficult given the inexorable prognosis of ALS. To fuel this discussion, this study describes the ICU and post-ICU survival of ALS-related ARF. MATERIAL AND METHODS: Retrospective cohort analysis over 10 years (university hospital setting, ALS reference center). RESULTS: Of 90 patients (66 men, median age: 67 [IQR 59-71], median interval since ALS diagnosis: 26.5 months [14-53], ALSFRS-R: 19 [12-30], bulbar signs 73%), 48 were managed by noninvasive ventilation (NIV) only, 7 were already tracheotomized upon admission, 12 were tracheotomized during the ICU stay (advance care planning project), 18 were already intubated before admission, 5 received oxygen and physiotherapy only. Median ICU stay was 4 days [2-9] with 20% mortality. Median hospital stay was 10 days [5-22] with 33% mortality. The 3-month and one year mortality wer 46% and 71%. Hospital mortality was higher in patients with more severe respiratory acidosis and higher simplified acute physiology scores on admission. CONCLUSIONS: The prognosis of ALS-related ARF requiring ICU admission resembles that of ARF complicating other conditions with high short-term mortality (e.g. lung cancer).

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.

Initiation of non-invasive ventilation in amyotrophic lateral sclerosis and clinical practice guidelines: Single-centre, retrospective, descriptive study in a national reference centre.

In amyotrophic lateral sclerosis (ALS), respiratory muscle weakness leads to respiratory failure. Non-invasive ventilation (NIV) maintains adequate ventilation in ALS patients. NIV alleviates symptoms and improves survival. In 2006, French guidelines established criteria for NIV initiation based on limited evidence. Their impact on clinical practice remains unknown. Our objective was to describe NIV initiation practices of the main French ALS tertiary referral centre with respect to guidelines. In this retrospective descriptive study, 624 patients followed in a single national reference centre began NIV between 2005 and 2013. We analysed criteria used to initiate NIV, including symptoms, PaCO2, forced vital capacity, maximal inspiratory pressures and time spent with SpO2 <90% at night. At NIV initiation, 90% of patients were symptomatic. Median PaCO2 was 48 mmHg. The main criterion to initiate NIV was 'symptoms' followed by 'hypercapnia' in 42% and 34% of cases, respectively. NIV was initiated on functional parameters in only 5% of cases. Guidelines were followed in 81% of cases. In conclusion, despite compliance with French guidelines, the majority of patients are treated at the stage of symptomatic daytime hypoventilation, which suggests that NIV is initiated late in the course of ALS. Whether this practice could be improved by changing guidelines or increasing respiratory-dedicated resources remains to be determined.

Small airway dysfunction in smokers with stable ischemic heart disease.

BACKGROUND: A higher prevalence of airflow limitation (AL) has been described in patients with ischemic heart disease (IHD). Although small airway dysfunction (SAD) is an early feature of AL, there is little information about its occurrence in IHD patients. Our objective was to describe the prevalence of SAD in IHD patients, while comparing patient-related outcomes and future health risk among IHD patients with AL, SAD and normal lung function. METHODS: In 118 consecutive smoking patients with stable IHD, comorbidities, utilization of healthcare resources, current treatment, blood biochemistry and health status were recorded. SAD was evaluated by impulse oscillometry, and pre- and post-bronchodilator spirometry was performed. RESULTS: The prevalence of AL and SAD were 20.3 (95% CI, 13.1-27.6%) and 26.3% (95% CI, 18.3-34.2%), respectively. Compared to the normal lung function group, patients with SAD and without AL had lower spirometric values, poorer quality of life and higher levels of C-reactive protein (CRP), as well as increased cardiovascular risk and more vascular age. In patients with normal spirometry, the presence of SAD was independently associated with pack-years, HDL-cholesterol and CRP levels. CONCLUSION: In patients with IHD, the presence of SAD is common and that it is associated with reduced health status and increased future cardiac risk.

Exercise oxygen flow titration methods in COPD patients with respiratory failure.

We compare the adequacy of several titration procedures of oxygen flow in maintaining SpO(2) > 90% during the activities of daily life in patients with very severe COPD. Thirty-one very severe COPD patients undergoing oxygen-therapy were recruited. Three titration methods were randomly performed: (1) 6-min walking tests; (2) cycle-ergometer constant work-rate tests at a load equivalent to 12 ml/min/kg of oxygen uptake; (3) one single constant work-rate test at 40 W 12-h pulse-oximeter monitoring was performed on four consecutive days with the following oxygen flow during exercise: 1 l·min(-1) above the resting prescription (NOTT guidelines) and those established by the titration procedures. The time spent SpO(2) < 90% was higher for the titration based on NOTT and walking tests than for the oxygen flow established by the constant work-rate tests at 12 ml O(2)/min/kg (22.1 ± 18.7, 20.8 ± 19.5 and 6.7 ± 12.7%, respectively). As for the oxygen uptake-based titration, the simplified procedure (a single exercise test at 40 w) generates longer times spent SpO(2) < 90% and SpO(2) < 85%, although it maintains a SpO(2) > 90% for more 90% of the time. In COPD patients, exercise oxygen flow titrations by NOTT guidelines or walking tests do not allow a suitable oxygenation during the activities of daily life. Two more adequate alternative methods, based on constant work-rate tests, are proposed.