Impact of Early Non-Invasive Ventilation in Amyotrophic Lateral Sclerosis: A multicenter Randomized Controlled Trial.

BACKGROUND AND OBJECTIVE: Forced vital capacity (FVC) less than 50% of predicted is one of the main parameters used for Non-Invasive Ventilation (NIV) initiation in Amyotrophic Lateral Sclerosis (ALS). Recent studies suggest that higher values of FVC could be considered as a threshold. The aim of this study is to evaluate whether early use of NIV improves the prognosis of ALS patients compared with standard initiation. METHODS: This is a randomized, parallel, multicenter, open-label, controlled clinical trial, with recruitment at the ALS outpatient multidisciplinary units of six Spanish hospitals. Patients were included when their FVC reached the 75% threshold and were randomized by computer, stratifying by center in an allocation ratio of 1:1 to Early NIV (FVC below 75%) or Standard NIV (FVC below 50%) initiation. The primary outcome was time to death or tracheostomy.Trial registration number ClinicalTrials.gov: NCT01641965. RESULTS: Between May 2012 and June 2014, 42 patients were randomized to two groups, 20 to Early NIV and 22 to Standard NIV initiation. We found differences in survival in favor of the intervention group: an incidence of mortality (2.68 [1.87-5.50] vs. 3.33 [1.34-4.80] person-months) and a median survival (25.2 vs. 19.4 months), although without reaching statistical significance (p = 0.267). CONCLUSIONS: This trial did not reach the primary endpoint of survival; nevertheless, it is the first Randomized Controlled Trial (RCT) to demonstrate the benefits of early NIV in slowing the decline of respiratory muscle strength and reducing adverse events. Although not all the results reached statistical significance, all the analyzed data favor early NIV. In addition, this study demonstrates good tolerance and compliance with early NIV without quality of sleep impairment. These data reinforce the early respiratory evaluation of ALS patients and NIV initiation with an FVC of around 75%.

Outcomes of COVID-19 Patients Admitted to the Intermediate Respiratory Care Unit: Non-Invasive Respiratory Therapy in a Sequential Protocol.

The intermediate respiratory care units (IRCUs) have a pivotal role managing escalation and de-escalation between the general wards and the intensive care units (ICUs). Since the COVID-19 pandemic began, the early detection of patients that could improve on non-invasive respiratory therapies (NRTs) in IRCUs without invasive approaches is crucial to ensure proper medical management and optimize limiting ICU resources. The aim of this study was to assess factors associated with survival, ICU admission and intubation likelihood in COVID-19 patients admitted to IRCUs. Observational retrospective study in consecutive patients admitted to the IRCU of a tertiary hospital from March 2020 to April 2021. Inclusion criteria: hypoxemic respiratory failure (SpO2 ≤ 94% and/or respiratory rate ≥ 25 rpm with FiO2 > 50% supplementary oxygen) due to acute COVID-19 infection. Demographic, comorbidities, clinical and analytical data, and medical and NRT data were collected at IRCU admission. Multivariate logistic regression models assessed factors associated with survival, ICU admission, and intubation. From 679 patients, 79 patients (12%) had an order to not do intubation. From the remaining 600 (88%), 81% survived, 41% needed ICU admission and 37% required intubation. In the IRCU, 51% required non-invasive ventilation (NIV group) and 49% did not (non-NIV group). Older age and lack of corticosteroid treatment were associated with higher mortality and intubation risk in the scheme, which could be more beneficial in severe forms. Initial NIV does not always mean worse outcomes.

Clinical Outcomes of Severe COVID-19 Patients Admitted to an Intermediate Respiratory Care Unit.

Introduction: Many severe COVID-19 patients require respiratory support and monitoring. An intermediate respiratory care unit (IMCU) may be a valuable element for optimizing patient care and limited health-care resources management. We aim to assess the clinical outcomes of severe COVID-19 patients admitted to an IMCU. Methods: Observational, retrospective study including patients admitted to the IMCU due to COVID-19 pneumonia during the months of March and April 2020. Patients were stratified based on their requirement of transfer to the intensive care unit (ICU) and on survival status at the end of follow-up. A multivariable Cox proportional hazards method was used to assess risk factors associated with mortality. Results: A total of 253 patients were included. Of them, 68% were male and median age was 65 years (IQR 18 years). Ninety-two patients (36.4%) required ICU transfer. Patients transferred to the ICU had a higher mortality rate (44.6 vs. 24.2%; p < 0.001). Multivariable proportional hazards model showed that age ≥65 years (HR 4.14; 95%CI 2.31-7.42; p < 0.001); chronic respiratory conditions (HR 2.34; 95%CI 1.38-3.99; p = 0.002) and chronic kidney disease (HR 2.96; 95%CI 1.61-5.43; p < 0.001) were independently associated with mortality. High-dose systemic corticosteroids followed by progressive dose tapering showed a lower risk of death (HR 0.15; 95%CI 0.06-0.40; p < 0.001). Conclusions: IMCU may be a useful tool for the multidisciplinary management of severe COVID-19 patients requiring respiratory support and non-invasive monitoring, therefore reducing ICU burden. Older age and chronic respiratory or renal conditions are associated with worse clinical outcomes, while treatment with systemic corticosteroids may have a protective effect on mortality.

Analysis of Blood Biomarkers in Patients with Chronic Obstructive Pulmonary Disease (COPD) and with Asthma-COPD Overlap (ACO).

Chronic obstructive pulmonary disease (COPD) is a heterogeneous entity with different clinical phenotypes, such as asthma-COPD overlap (ACO). The aim of this retrospective study was to compare routine blood biomarkers in patients with ACO and the remaning COPD phenotypes. Data were collected from stable COPD patients visited in during 2018, including C-reactive protein (CRP), fibrinogen, neutrophyl/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR).A total of 77 patients with COPD were included, 24 (31%) fulfilled the diagnosis of ACO. Clinically, patients with ACO presented more dyspnoea and wheezing. Regarding laboratory parameters, both groups had low levels of lymphocytes, especially the non-ACO group (24.2% vs. 29.3%; p = 0.031), patients with ACO had significantly higher eosinophil counts (4.7% vs. 1.9%; p < 0.001) but a lower percentage of neutrophils (56.8% vs. 64.7%; p = 0.003), NLR and PLR (2.5 vs. 3.8; p = 0.013 and 115 vs. 160; p = 0.063, respectively). In conclusion, besides the expected eosinophilic inflammation in patients with ACO, both groups had low levels of lymphocytes, especially the non-ACO group. The low levels of lymphocytes, in particular in non-ACO patients, should be confirmed in larger studies.

Practical Guide to the Identification and Diagnosis of Asthma-COPD Overlap (ACO).

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of mortality around the world. COPD is characterised by a heterogeneous clinical presentation and prognosis which may vary according to the clinical phenotype. One of the phenotypes of COPD most frequently studied is the asthma-COPD overlap (ACO), however, there are no universally accepted diagnostic criteria for ACO. It is recognised that the term ACO includes patients with clinical features of both asthma and COPD, such as more intense eosinophilic bronchial inflammation, more severe respiratory symptoms and more frequent exacerbations, but in contrast, it is associated with a better prognosis compared to COPD. More importantly, ACO patients show better response to inhaled corticosteroid treatment than other COPD phenotypes. The diagnosis of ACO can be difficult in clinical practice, and the identification of these patients can be a challenge for non-specialized physicians. We describe how to recognise and diagnose ACO based on a recently proposed Spanish algorithm and by the analysis of three clinical cases of patients with COPD. The diagnosis of ACO is based on the diagnosis of COPD (chronic airflow obstruction in an adult with significant smoking exposure), in addition to a current diagnosis of asthma and/or signficant eosinophilia.