Daily Respiratory Research Analysis

BACKGROUND: Despite the increasing use of non-invasive respiratory support in paediatric intensive care units, there are no large randomised controlled trials comparing two commonly used non-invasive respiratory support modes, continuous positive airway pressure and high-flow nasal cannula therapy. OBJECTIVE: To evaluate the non-inferiority of high-flow nasal cannula, compared with continuous positive airway pressure, when used as the first-line mode of non-invasive respiratory support in acutely ill children and following extubation, on time to liberation from respiratory support, defined as the start of a 48-hour period during which the child was free of respiratory support (non-invasive and invasive). DESIGN: A master protocol comprising two pragmatic, multicentre, parallel-group, non-inferiority randomised controlled trials (step-up and step-down) with shared infrastructure, including internal pilot and integrated health economic evaluation. SETTING: Twenty-five National Health Service paediatric critical care units (paediatric intensive care units and/or high-dependency units) across England, Wales and Scotland. PARTICIPANTS: Critically ill children assessed by the treating clinician to require non-invasive respiratory support for (1) acute illness (step-up randomised controlled trial) or (2) within 72 hours of extubation (step-down randomised controlled trial). INTERVENTIONS: High-flow nasal cannula delivered at a flow rate based on patient weight (Intervention) compared to continuous positive airway pressure of 7-8 cm H MAIN OUTCOME MEASURES: The primary clinical outcome was time to liberation from respiratory support. The primary cost-effectiveness outcome was 180-day incremental net monetary benefit. Secondary outcomes included mortality at paediatric intensive care unit/high-dependency unit discharge, day 60 and day 180; (re)intubation rate at 48 hours; duration of paediatric intensive care unit/high-dependency unit and hospital stay; patient comfort; sedation use; parental stress; and health-related quality of life at 180 days. RESULTS: In the step-up randomised controlled trial, out of 600 children randomised, 573 were included in the primary analysis (median age 9 months). Median time to liberation was 52.9 hours for high-flow nasal cannula (95% confidence interval 46.0 to 60.9 hours) and 47.9 hours (95% confidence interval 40.5 to 55.7 hours) for continuous positive airway pressure (adjusted hazard ratio 1.03, one-sided 97.5% confidence interval 0.86 to ∞). The high-flow nasal cannula group had lower use of sedation (27.7% vs. 37%) and mean duration of acute hospital stay (13.8 days vs. 19.5 days). In the step-down randomised controlled trial, of the 600 children randomised, 553 were included in the primary analysis (median age 3 months). Median time to liberation for high-flow nasal cannula was 50.5 hours (95% confidence interval, 43.0 to 67.9) versus 42.9 hours (95% confidence interval 30.5 to 48.2) for continuous positive airway pressure (adjusted hazard ratio 0.83, one-sided 97.5% confidence interval 0.70 to ∞). Mortality at day 180 was significantly higher for high-flow nasal cannula [5.6% vs. 2.4% for continuous positive airway pressure, adjusted odds ratio, 3.07 (95% confidence interval, 1.1 to 8.8)]. LIMITATIONS: The interventions were unblinded. A heterogeneous cohort of children with a range of diagnoses and severity of illness were included. CONCLUSIONS: Among acutely ill children requiring non-invasive respiratory support, high-flow nasal cannula met the criterion for non-inferiority compared with continuous positive airway pressure for time to liberation from respiratory support whereas in critically ill children requiring non-invasive respiratory support following extubation, the non-inferiority of high-flow nasal cannula could not be demonstrated. FUTURE WORK: (1) Identify risk factors for treatment failure. (2) Compare protocolised approaches to post-extubation non-invasive respiratory support, with standard care. (3) Explore alternative approaches for evaluating heterogeneity of treatment effect. (4) Explore reasons for increased mortality in high-flow nasal cannula group within step-down randomised controlled trial. STUDY REGISTRATION: Current Controlled Trials ISRCTN60048867.

BACKGROUND: During the 2023 wildfire season, Ontario, Canada, had unprecedented wildfire smoke, but the health impact on the population is unknown. We aimed to quantify the acute impact of the wildfire smoke on respiratory and cardiovascular outcomes across Ontario. METHODS: We conducted a quasi-experimental study by leveraging the timing of 2 consecutive wildfire smoke episodes in June 2023. Heavy wildfire smoke blanketed much of Ontario on 2 occasions, in early June and again in late June, causing severely degraded daily air quality. Following the epidemiologic triangulation framework, we collected health data on emergency department visits for 4 outcomes (asthma-related causes, other respiratory causes, ischemic heart disease, and non-cardiorespiratory causes) from Ontario's real-time syndromic surveillance system and the National Ambulatory Care Reporting System. We also employed different epidemiologic methodologies, including interrupted time-series and case-crossover analyses. RESULTS: After the initial heavy wildfire smoke in early June 2023, daily asthma-related visits increased substantially across Ontario, peaking at a 23.6% increase (95% confidence interval 13.2%-34.9%) at a 1-day lag and lasting up to a lag of 5 days after the start of the smoke episode. The later episode of heavy smoke, despite causing higher exposures, had a reduced effect on asthma-related visits. We did not detect any effect on other outcomes in either episode. These findings were consistent across different methodologies and data sources. Post hoc analysis revealed that asthma-related visits were briefly elevated after the wildfire smoke among children (40% higher), but we observed a more sustained effect among adults (48% higher, lasting 1 week). INTERPRETATION: The 2023 wildfires substantially increased asthma-related emergency department visits in Ontario, with age and timing of exposure being important factors influencing the impact. As wildfires emerge as one of the fastest-growing environmental risk factors globally, future research should identify and evaluate measures to effectively mitigate the acute health impacts of wildfire smoke.

BACKGROUND: Globally, chronic respiratory diseases have become the third leading cause of death, including chronic obstructive pulmonary disease (COPD) and asthma, and have been threatening human life for a long time. To alleviate the disease burden, it is crucial to develop rapid and convenient screening methods for COPD, preserved ratio impaired spirometry (PRISm), and asthma. Volatile organic compounds (VOCs) in breath can reflect the pathophysiological processes of disease, thereby having the potential to serve as a promising approach for diagnosing respiratory diseases. Can we identify VOC markers in breath with the potential to serve as classification indicators, and further establish learning models for the early detection of COPD, asthma, or PRISm patients? METHODS: This is a cross-sectional study in which exhaled breath samples were collected from 184 patients with COPD, 66 patients with asthma, 72 PRISm individuals, and 45 healthy individuals. From August 2023 to June 2024, the breath samples were analyzed using portable micro gas chromatography (CXBA-Alpha, ChromX Health Co., Ltd.). Potential VOC markers for classification were identified by univariate and multivariate analyses. Subsequently, classification models were established by machine learning algorithms, based on these VOC markers along with baseline characteristics. The sensitivity, specificity, and accuracy of these models were calculated to assess their overall discriminatory performance. RESULTS: A total of 367 patients were enrolled in our study. We identified nine VOCs distinguishing COPD patients from healthy controls, nine VOCs differentiating the PRISm population from healthy controls, five VOCs separating asthma patients from healthy controls, five VOCs distinguishing COPD patients from asthma patients, and seven VOCs differentiating the PRISm population from asthma patients based on breathomics feature selection. We utilized five algorithms to establish diagnostic models and selected the optimal one among them. The random forest model best distinguished COPD from healthy controls with an area under the receiver operating characteristic curve (AUC) of 0.92 ± 0.01. The support vector classifier (SVC) model was most effective in separating PRISm from healthy controls, achieving an AUC of 0.78 ± 0.01. Logistic regression performed well in discriminating asthma from PRISm (AUC, 0.74 ± 0.02) and COPD (AUC, 0.92 ± 0.01), in contrast, the random forest model differentiated asthma from healthy controls with an AUC of 0.81 ± 0.02. CONCLUSION: VOC panel-based classification models have the potential to be a novel strategy for the discrimination of chronic respiratory diseases. Using the portal micro gas chromatography enables swift detection of chronic respiratory disease and, most importantly, facilitates the rapid identification of PRISm individuals within the population.