Nasal versus oronasal masks for home non-invasive ventilation in patients with chronic hypercapnia: a systematic review and individual participant data meta-analysis.

BACKGROUND: The optimal interface for the delivery of home non-invasive ventilation (NIV) to treat chronic respiratory failure has not yet been determined. The aim of this individual participant data (IPD) meta-analysis was to compare the effect of nasal and oronasal masks on treatment efficacy and adherence in patients with COPD and obesity hypoventilation syndrome (OHS). METHODS: We searched Medline and Cochrane Central Register of Controlled Trials for prospective randomised controlled trials (RCTs) of at least 1 month's duration, published between January 1994 and April 2019, that assessed NIV efficacy in patients with OHS and COPD. The main outcomes were diurnal PaCO2, PaO2 and NIV adherence (PROSPERO CRD42019132398). FINDINGS: Of 1576 articles identified, 34 RCTs met the inclusion criteria and IPD were obtained for 18. Ten RCTs were excluded because only one type of mask was used, or mask data were missing. Data from 8 RCTs, including 290 IPD, underwent meta-analysis. Oronasal masks were used in 86% of cases. There were no differences between oronasal and nasal masks for PaCO2 (0.61 mm Hg (95% CI -2.15 to 3.38); p=0.68), PaO2 (-0.00 mm Hg (95% CI -4.59 to 4.58); p=1) or NIV adherence (0·29 hour/day (95% CI -0.74 to 1.32); p=0.58). There was no interaction between the underlying pathology and the effect of mask type on any outcome. INTERPRETATION: Oronasal masks are the most used interface for the delivery of home NIV in patients with OHS and COPD; however, there is no difference in the efficacy or tolerance of oronasal or nasal masks.

Predictors of respiratory complications in patients with C5-T5 spinal cord injuries.

STUDY DESIGN: Retrospective chart audit. OBJECTIVES: Describing the respiratory complications and their predictive factors in patients with acute traumatic spinal cord injuries at C5-T5 level during the initial hospitalization. SETTING: Hospital Vall d'Hebron, Barcelona. METHODS: Data from patients admitted in a reference unit with acute traumatic injuries involving levels C5-T5. Respiratory complications were defined as: acute respiratory failure, respiratory infection, atelectasis, non-hemothorax pleural effusion, pulmonary embolism or haemoptysis. Candidate predictors of these complications were demographic data, comorbidity, smoking, history of respiratory disease, the spinal cord injury characteristics (level and ASIA Impairment Scale) and thoracic trauma. A logistic regression model was created to determine associations between potential predictors and respiratory complications. RESULTS: We studied 174 patients with an age of 47.9 (19.7) years, mostly men (87%), with low comorbidity. Coexistent thoracic trauma was found in 24 (19%) patients with cervical and 35 (75%) with thoracic injuries (p < 0.001). Respiratory complications were frequent (53%) and were associated to longer hospital stay: 83.1 (61.3) and 45.3 (28.1) days in patients with and without respiratory complications (p < 0.001). The strongest predictors of respiratory complications were: previous respiratory disease (OR 5.4, 95% CI: 1.5-19.2), complete motor function impairment (AIS A-B) (OR 4.7, 95% CI: 2.4-9.5) and concurrent chest trauma (OR 3.73, 95% CI: 1.8-7.9). CONCLUSIONS: Respiratory complications are common in traumatic spinal cord injuries between C5-T5. We identified previous respiratory disease, complete motor function impairment and the coexistence of thoracic trauma as predictors of respiratory complications. Identification of patients at risk might help clinicians to implement preventive strategies.

Non-invasive ventilation in obesity hypoventilation syndrome without severe obstructive sleep apnoea.

BACKGROUND: Non-invasive ventilation (NIV) is an effective form of treatment in patients with obesity hypoventilation syndrome (OHS) who have concomitant severe obstructive sleep apnoea (OSA). However, there is a paucity of evidence on the efficacy of NIV in patients with OHS without severe OSA. We performed a multicentre randomised clinical trial to determine the comparative efficacy of NIV versus lifestyle modification (control group) using daytime arterial carbon dioxide tension (PaCO2) as the main outcome measure. METHODS: Between May 2009 and December 2014 we sequentially screened patients with OHS without severe OSA. Participants were randomised to NIV versus lifestyle modification and were followed for 2 months. Arterial blood gas parameters, clinical symptoms, health-related quality of life assessments, polysomnography, spirometry, 6-min walk distance test, blood pressure measurements and healthcare resource utilisation were evaluated. Statistical analysis was performed using intention-to-treat analysis. RESULTS: A total of 365 patients were screened of whom 58 were excluded. Severe OSA was present in 221 and the remaining 86 patients without severe OSA were randomised. NIV led to a significantly larger improvement in PaCO2 of -6 (95% CI -7.7 to -4.2) mm Hg versus -2.8 (95% CI -4.3 to -1.3) mm Hg, (p<0.001) and serum bicarbonate of -3.4 (95% CI -4.5 to -2.3) versus -1 (95% CI -1.7 to -0.2 95% CI)  mmol/L (p<0.001). PaCO2 change adjusted for NIV compliance did not further improve the inter-group statistical significance. Sleepiness, some health-related quality of life assessments and polysomnographic parameters improved significantly more with NIV than with lifestyle modification. Additionally, there was a tendency towards lower healthcare resource utilisation in the NIV group. CONCLUSIONS: NIV is more effective than lifestyle modification in improving daytime PaCO2, sleepiness and polysomnographic parameters. Long-term prospective studies are necessary to determine whether NIV reduces healthcare resource utilisation, cardiovascular events and mortality. TRIAL REGISTRATION NUMBER: NCT01405976; results.

Poor sleep quality, COPD severity and survival according to CASIS and Pittsburgh questionnaires.

Poor sleep quality is frequent among COPD patients and it has been related to worse outcomes. The objective of this study was to compare the COPD and Asthma Sleep Impact Scale (CASIS) and the generic Pittsburgh Sleep Quality Index (PSQI) questionnaires as reliable tools for evaluating sleep quality and its relationship with COPD characteristics and survival. Stable COPD patients were prospectively evaluated. Anthropometric, sociodemographic, comorbidity, lung function and treatment data were collected. All patients completed CASIS and PSQI, mMRC dyspnea severity scale, COPD Assessment Test (CAT), sleep apnoea STOP-Bang and Hospital Anxiety and Depression Scale (HADS) questionnaires. Body mass index, airflow Obstruction, Dyspnea and Exacerbations (BODEx) index was calculated. Life status was determined after a mean follow-up of 3.7 (SD 1) years. We included 200 patients, 69.5% male, mean age 65.8 (9) years. Poor sleep was detected in 100 (50%) and 84 patients (42%) according to PSQI and CASIS questionnaires, respectively, with an agreement of 63%. Poor sleep was related to female gender, more severe dyspnea and worse BODEx, HADS and CAT scores according to both questionnaires. PSQI was associated to chronic pain or inferior urinary tract symptoms and CASIS to exacerbations, shorter walked distance in the 6-min walking test and treatment with oral corticosteroids or chronic oxygen. Thirty nine (19.5%) patients died during follow-up. Mortality was not associated to PSQI nor CASIS results. Unlike PSQI, CASIS is more related to COPD severity and its results are not influenced by comorbidities with known impact on sleep quality. In our sample, poor sleep quality was not associated with increased mortality.

Long-term effect of tocilizumab on mortality, readmissions, persistent symptoms and lung function in SARS-CoV-2 patients 1 year after hospital discharge: A matched cohort study.

BACKGROUND: Tocilizumab is presumed to be an effective and safe treatment for severe SARS-Cov-2, but its usefulness has not been investigated yet for long-term outcomes. This study aimed to evaluate the influence of tocilizumab on mortality in patients with SARS-CoV-2 throughout the year following discharge. METHODS: A retrospective observational analysis was performed on electronic medical records of patients with SARS-CoV2 who were discharged from our hospital after surviving the first wave in March-April 2020. Logistic regression was used to analyse the effect of tocilizumab on mortality, as the main outcome, and propensity-score analysis to further validate their effect. Secondary outcomes were readmissions, persistent symptoms and lung function evolution. Patients were selected by matching their individual propensity for receiving therapy with tocilizumab, conditional on their demographic and clinical variables. RESULTS: A total of 405 patients were included in the mortality study (33.6 % were treated with tocilizumab) and 390 were included in the assessment of persistent symptoms. After propensity-score analysis, no association between tocilizumab use and 1-year overall mortality was found (HR= 2.05, 95 % CI: 0.21-19.98). No differences regarding persistent symptoms (OR= 1.01 95 %CI 0.57-1.79), nor lung function parameters (forced vital capacity: coefficient -0.16 95 %CI -0.45 to 0.14) were found throughout the year follow-up between control and tocilizumab group. CONCLUSIONS: The administration of tocilizumab in patients with SARS-CoV-2 did not show any effect on long-term mortality. Identically, no association were found regarding readmissions, persistent symptoms or lung function evolution and tocilizumab administration in our cohort of patients after 1 year follow-up.

Effect of Intensity of Home Noninvasive Ventilation in Individuals With Neuromuscular and Chest Wall Disorders: A Systematic Review and Meta-Analysis of Individual Participant Data.

INTRODUCTION: Home noninvasive ventilation (NIV), targeting a reduction of carbon dioxide with a combination of sufficient inspiratory support and backup-rate improves outcomes in patients with chronic obstructive pulmonary disease. The aim of this systematic review with individual participant data (IPD) meta-analysis was to evaluate the effects of intensity of home NIV on respiratory outcomes in individuals with slowly progressive neuromuscular (NMD) or chest-wall disorders (CWD). METHODS: Controlled, non-controlled and cohort studies indexed between January-2000 and December-2020 were sought from Medline, Embase and the Cochrane Central Register. Outcomes were diurnal PaCO2, PaO2, daily NIV usage, and interface type (PROSPERO-CRD 42021245121). NIV intensity was defined according to the Z-score of the product of pressure support (or tidal volume) and backup-rate. RESULTS: 16 eligible studies were identified; we obtained IPD for 7 studies (176 participants: 113-NMD; 63-CWD). The reduction in PaCO2 was greater with higher baseline PaCO2. NIV intensity per se was not associated with improved PaCO2 except in individuals with CWD and the most severe baseline hypercapnia. Similar results were found for PaO2. Daily NIV usage was associated with improvement in gas exchange but not with NIV intensity. No association between NIV intensity and interface type was found. CONCLUSION: Following home NIV initiation in NMD or CWD patients, no relationship was observed between NIV intensity and PaCO2, except in individuals with the most severe CWD. The amount of daily NIV usage, rather than intensity, is key to improving hypoventilation in this population during the first few months after introduction of therapy.

Impact of home CPAP-treated obstructive sleep apnea on COVID-19 outcomes in hospitalized patients.

STUDY OBJECTIVES: To investigate the association between moderate or severe obstructive sleep apnea treated with home continuous positive airway pressure (CPAP) and severe coronavirus disease 2019 (COVID-19). METHODS: Retrospective study of patients admitted for COVID-19. Patients with obstructive sleep apnea treated with home CPAP were identified and for each of them we selected 5 patients admitted consecutively in the following hours. The main outcome of the study was the development of severe COVID-19, defined as 1) death or 2) a composite outcome of death or the presence of severe hypoxemic respiratory failure at or during admission. The association between CPAP-treated obstructive sleep apnea and these outcomes was estimated by logistic regression analysis after applying inverse probability of treatment weighting using a propensity score-weighting approach. RESULTS: Of the 2,059 patients admitted, 81 (3.9%) were receiving treatment with home CPAP. Among the 486 patients included in the study, 19% died and 39% presented the composite outcome. The logistic regression analysis did not show an association of CPAP treatment either with death (odds ratio [OR]: 0.684; 95% confidence interval [CI]: 0.332-1.409; P = .303) or with the composite outcome (OR: 0.779; 95% CI: 0.418-1.452; P = .432). Death was associated with age (OR: 1.116; 95% CI: 1.08-1.152; P < .001) and number of comorbidities (OR: 1.318; 95% CI: 1.065-1.631; P = .012), and the composite outcome was associated with male sex (OR: 2.067; 95% CI: 1.19-3.589; P = .01) and number of comorbidities (OR: 1.241; 95% CI: 1.039-1.484; P = .018). CONCLUSIONS: In hospitalized patients with COVID-19, prior obstructive sleep apnea treated with home CPAP is not independently associated with worse outcomes. CITATION: Sampol J, Sáez M, Martí S, et al. Impact of home CPAP-treated obstructive sleep apnea on COVID-19 outcomes in hospitalized patients. J Clin Sleep Med. 2022;18(7):1857-1864.

Sleep increases leaks and asynchronies during home noninvasive ventilation: a polysomnographic study.

STUDY OBJECTIVES: In patients treated with noninvasive ventilation, sleep-related breathing changes can modify patient-ventilator interactions, which could reduce its effectiveness. The aim of this prospective observational study was to determine the impact of sleep/wake state on leaks, upper airway obstructive events, and asynchronies in patients treated by long-term noninvasive ventilation. METHODS: Stable patients adapted to noninvasive ventilation were considered for nocturnal polysomnography. Unintentional leaks, upper airway obstructive events, and asynchronies were compared between sleep and awake periods. RESULTS: Twenty-eight patients were enrolled. Underlying diagnoses were neuromuscular disease (n = 11), chest wall disease (n = 8), and obesity-hypoventilation (n = 9). Leaks were more frequent in sleep than in awake periods, with a median of 10% (interquartile range [IQR], 0%-75%) vs 1% (IQR, 0%-9%) of time (P < .001), respectively. During sleep, asynchronies with and without associated leak affected 27% of breaths (IQR, 16%-39%) compared with non-leak-related asynchronies that were recorded in 8% (IQR, 3%-25%) of breaths (P < .001). Asynchronies affecting more than 10% of total breaths were more frequent in sleep (25 patients, 89%) than in awake time (8 patients, 29%; P = .25). Eleven patients (39%) presented with 5 or more upper airway obstructive events without reduction in ventilatory drive per hour of sleep. CONCLUSIONS: In patients adapted to home noninvasive ventilation, leaks, asynchronies, and upper airway obstructive events are frequent during the night and are concentrated in sleep periods. Asynchronies are often associated with leaks. These findings may have clinical implications considering that in patients with low sleep efficiency respiratory events could be underestimated if sleep is not evaluated. CITATION: Martí S, Ferré A, Sampol G, et al. Sleep increases leaks and asynchronies during home noninvasive ventilation: a polysomnographic study. J Clin Sleep Med. 2022;18(1):225-233.

Higher mortality and intubation rate in COVID-19 patients treated with noninvasive ventilation compared with high-flow oxygen or CPAP.

The effectiveness of noninvasive respiratory support in severe COVID-19 patients is still controversial. We aimed to compare the outcome of patients with COVID-19 pneumonia and hypoxemic respiratory failure treated with high-flow oxygen administered via nasal cannula (HFNC), continuous positive airway pressure (CPAP) or noninvasive ventilation (NIV), initiated outside the intensive care unit (ICU) in 10 university hospitals in Catalonia, Spain. We recruited 367 consecutive patients aged ≥ 18 years who were treated with HFNC (155, 42.2%), CPAP (133, 36.2%) or NIV (79, 21.5%). The main outcome was intubation or death at 28 days after respiratory support initiation. After adjusting for relevant covariates and taking patients treated with HFNC as reference, treatment with NIV showed a higher risk of intubation or death (hazard ratio 2.01; 95% confidence interval 1.32-3.08), while treatment with CPAP did not show differences (0.97; 0.63-1.50). In the context of the pandemic and outside the intensive care unit setting, noninvasive ventilation for the treatment of moderate to severe hypoxemic acute respiratory failure secondary to COVID-19 resulted in higher mortality or intubation rate at 28 days than high-flow oxygen or CPAP. This finding may help physicians to choose the best noninvasive respiratory support treatment in these patients.Clinicaltrials.gov identifier: NCT04668196.

Overexpression of a pine Dof transcription factor in hybrid poplars: A comparative study in trees growing under controlled and natural conditions.

In this work, the role of the pine transcriptional regulator Dof 5 in carbon and nitrogen metabolism has been examined in poplar trees. The overexpression of the gene and potential effects on growth and biomass production were compared between trees growing in a growth chamber under controlled conditions and trees growing in a field trial during two growth seasons. Ten-week-old transgenic poplars exhibited higher growth than untransformed controls and exhibited enhanced capacity for inorganic nitrogen uptake in the form of nitrate. Furthermore, the transgenic trees accumulated significantly more carbohydrates such as glucose, fructose, sucrose and starch. Lignin content increased in the basal part of the stem likely due to the thicker stem of the transformed plants. The enhanced levels of lignin were correlated with higher expression of the PAL1 and GS1.3 genes, which encode key enzymes involved in the phenylalanine deamination required for lignin biosynthesis. However, the results in the field trial experiment diverged from those observed in the chamber system. The lines overexpressing PpDof5 showed attenuated growth during the two growing seasons and no modification of carbon or nitrogen metabolism. These results were not associated with a decrease in the expression of the transgene, but they can be ascribed to the nitrogen available in the field soil compared to that available for growth under controlled conditions. This work highlights the paramount importance of testing transgenic lines in field trials.

Ambulatory adaptation to noninvasive ventilation in restrictive pulmonary disease: a randomized trial with cost assessment.

BACKGROUND: Home mechanical ventilation is usually initiated in hospital. However, cost-effectiveness of inpatient set up has never been compared to outpatient adaptation in a randomized design. A Prospective, multicenter, non-inferiority trial was conducted comparing the effectiveness of adaptation to noninvasive mechanical ventilation (NIMV) performed in the ambulatory or hospital setting in patients with chronic respiratory failure secondary to restrictive thoracic disease, obesity-hypoventilation syndrome or neuromuscular disease. METHODS: The study included 53 candidates for NIMV, randomized to ambulatory adaptation (AA) (n = 27) or hospital adaptation (HA) (n = 26). The patients' characteristics were recorded before establishing ventilation and at 1 and 6 months after. The main outcome variable was PaCO2 decrease at 6 months following initiation of NIMV. The direct costs of the two interventions were compared. RESULTS: Before starting NIMV, PaCO2 was 50.4 ± 6.8 mmHg in the AA group and 50.3 ± 5.7 mmHg in the HA group. At 6 months of NIMV use, a significant improvement in PaCO2 relative to baseline was found in both groups: mean (95% CI) PaCO2 decrease was 4.9 (2.3; 7.4) mmHg in AA and 3.3 (1.4; 5.1) mmHg in HA. The direct calculated cost was 1500 euros per patient in AA and 2692 euros per patient in HA. CONCLUSIONS: Adaptation to NIMV in the ambulatory setting is not inferior to hospital adaptation in terms of therapeutic equivalence in stable patients with chronic respiratory failure secondary to restrictive thoracic disease, obesity-hypoventilation syndrome or neuromuscular disease. Outpatient adaptation may represent a cost saving for the healthcare system. CLINICAL TRIAL: Identifier number NCT00698958 at www.clinicaltrials.gov.

Predictors of mortality in chest wall disease treated with noninvasive home mechanical ventilation.

RATIONALE: The long-term evolution of patients with chest wall disease and chronic respiratory failure treated with noninvasive home mechanical ventilation (NIHMV) is poorly known. OBJECTIVES: The aim of this prospective observational study was to analyze the variables associated with mortality in a cohort of chest wall disease patients with chronic respiratory failure undergoing long-term follow-up after starting treatment with NIHMV. METHODS: Chest wall disease patients who began NIHMV between 1996 and 2005 were followed up, with death as the primary outcome. The patients' clinical characteristics, lung function, and arterial blood gases were recorded at the start of treatment. Patients were seen and evaluated 1 month after starting NIHMV. The prognostic value of clinical and functional variables were assessed by Cox regression analyses. MAIN RESULTS: We included 110 patients, 61 with tuberculosis sequelae and 49 with kyphoscoliosis. By the end of follow-up, 34 patients (28%) had died. The 5-year survival was 69% in those with tuberculosis sequelae and 75% in kyphoscoliosis. PaCO(2) ≥50 mmHg at 1 month of home ventilation and comorbidity (Charlson Index ≥3) were independent predictors of mortality. CONCLUSION: Our results suggest that PaCO2 levels ≥50 mmHg at 1 month after starting noninvasive home mechanical ventilation and the presence of comorbid conditions are risk factors for mortality in patients with chest wall disease. The importance of early detection of suboptimal home ventilation as well as comorbidities is highlighted.