Daily Respiratory Research Analysis

BACKGROUND: The effect of higher positive end-expiratory pressure (PEEP) and recruitment manoeuvres aimed at lung expansion as compared with lower PEEP without recruitment manoeuvres aimed at permissive atelectasis on postoperative pulmonary complications (PPCs) in patients undergoing one-lung ventilation (OLV) during thoracic surgery is unclear. We aimed to determine the contribution of an intraoperative lung expansion strategy to preventing PPCs. METHODS: In this multicentre, randomised, controlled, international phase 3 trial (PROTHOR) conducted at 74 sites in 28 countries, we enrolled adult patients (aged ≥18 years) with a BMI of less than 35 kg/m FINDINGS: Between Jan 3, 2017, and Feb 12, 2024, 2200 patients were randomly allocated: 1099 to the high PEEP group and 1101 to the low PEEP group. 43 patients in the high PEEP group and 33 in the low PEEP group were excluded from the modified intention-to-treat analysis after randomisation. The primary outcome occurred in 555 (53·6%) of 1036 patients in the high PEEP group and 592 (56·4%) of 1049 patients in the low PEEP group (absolute risk difference -2·68 percentage points [95% CI -6·36 to 1·01]; p=0·155). Intraoperative complications occurred in 484 (49·8%) of 972 patients in the high PEEP group and in 305 (31·3%) of 974 patients in the low PEEP group (absolute risk difference 18·09 percentage points [95% CI 14·41-21·77]), among which hypotension (360 [37·3%] of 966 patients in the high PEEP group vs 140 [14·3%] of 978 in the low PEEP group) and new arrhythmias (89 [9·9%] of 899 vs 37 [3·9%] of 956) were more frequent in the high PEEP group, while hypoxaemia rescue manoeuvres were more frequent in the low PEEP group (29 [3·3%] of 888 vs 86 [8·8%] of 982). The proportions of patients with extrapulmonary postoperative complications (110 [10·6%] of 1036 vs 107 [10·2%] of 1049 patients), and the numbers of adverse events (209 vs 204 events), did not differ between groups. INTERPRETATION: In patients with a BMI of less than 35 kg/m FUNDING: Clinical Trials Network of the European Society of Anaesthesiology and Intensive Care; Department of Anaesthesiology and Intensive Care, University Hospital Carl Gustav Carus, Technische Universität Dresden (Dresden, Germany); Conselho Nacional de Desenvolvimento Científico e Tecnológico (Brasília, Brazil); and the Association of Anaesthetists of GB and Ireland.

OBJECTIVES: This study aimed to evaluate the associations between inhaled corticosteroids (ICSs) and adverse events (AEs) in adults with asthma or chronic obstructive pulmonary disease (COPD) and to explore variations by ICS type and dosage. DESIGN AND SETTING: Medline/PubMed, Embase, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov were searched from inception to 20 February 2025. Data extraction and synthesis were performed, estimating risk ratios (RRs) with 95% confidence intervals (CI) or credible intervals (CrI) through pairwise and network meta-analysis (NMA), and an NMA using the Emax model was employed to find the dose-response relationships of the AEs of each ICS. Risk of bias was evaluated across both pairwise and NMAs. The certainty of evidence, based on the GRADE approach, was assessed exclusively for the NMA estimates. PARTICIPANTS: Adults diagnosed with asthma or COPD treated with ICSs compared with non-ICS controls or those receiving different types or doses of ICSs. MAIN OUTCOME MEASURES: The primary outcomes were AEs, including pneumonia, oral candidiasis, upper respiratory tract infection (URTI), fracture, diabetes, cataract and plasma cortisol abnormalities. Secondary outcomes included efficacy-related endpoints: asthma exacerbations, COPD exacerbations and all-cause mortality. RESULTS: 129 trials (120 900 participants) were included. According to pairwise meta-analysis, ICSs were associated with a higher risk of pneumonia (RR 1.49, 95% CI 1.38 to 1.61) and oral candidiasis (RR 2.29, 95% CI 2.01 to 2.60) and with a slightly higher risk of URTI (RR 1.17, 95% CI 1.10 to 1.25), compared with control. Besides, ICSs were linked to a reduced risk of asthma exacerbations (RR 0.30, 95% CI 0.20 to 0.45) and COPD exacerbations (RR 0.90, 95% CI 0.86 to 0.94) vs control. The results of the NMA that explored differences by ICS type showed that beclomethasone and fluticasone increased pneumonia risk compared with control, with absolute risk increases of up to 2.3%. Fluticasone also showed a slightly higher pneumonia risk than budesonide. Besides, mometasone, beclomethasone, budesonide and fluticasone were associated with increased risk of oral candidiasis, with the highest increase observed for mometasone (4.3%). In contrast, ciclesonide consistently showed lower risk across comparisons, reducing oral candidiasis by up to 4.5% with other ICSs. Fluticasone modestly increased URTI, while ciclesonide reduced it. Budesonide and mometasone were also associated with a small increase in cataract risk. Most of the outcomes reported here were supported by moderate- to high-certainty evidence. Furthermore, the dose-response relationship estimated from the Emax model indicated significant associations between fluticasone dose and the risks of pneumonia and URTI, between multiple ICS doses and oral candidiasis and between budesonide dose and cataract. CONCLUSIONS: ICSs are correlated with the escalated risk of pneumonia, oral candidiasis and URTI in adult patients with asthma or COPD, but ICSs could reduce asthma exacerbations and COPD exacerbations. Fluticasone, beclomethasone, budesonide and mometasone are independently linked to certain AEs, and some Emax dose-response relationships are detected.Our findings may help guide individualised ICS use by informing benefit-risk considerations across various formulations and dosing regimens. PROSPERO REGISTRATION NUMBER: CRD42024527797.

BACKGROUND: Pulmonary exacerbations (PExs) are associated with lung function decline and poor quality of life in people with cystic fibrosis (CF). Standard clinical measurements are limited in predicting future PEx events; pulmonary MRI scan has been shown to be a sensitive measure of CF lung disease, but its ability to predict PExs is currently unknown. RESEARCH QUESTION: Are people with worse structural lung MRI scores and xenon MRI ventilation defects at greater risk of PExs, and are these measurements associated with future PExs? STUDY DESIGN AND METHODS: We retrospectively analyzed clinical, imaging, and spirometry data collected from 106 patients with CF 6 to 45 years of age including ultrashort echo time (UTE) MRI scan and RESULTS: Patients who experienced PEx within 2 years after MRI scan had greater VDP, and VDP was higher in those with frequent exacerbations. People with abnormal VDP (> 3%) had a nearly 3 times (2.80; 95% CI, 1.6-4.56) greater PEx incidence rate. There were increased exacerbations among those with the most severe UTE MRI scores (fourth quartile) for consolidation, wall thickening, and bronchiectasis. Multivariable PEx prediction models that included imaging were stronger than those that included clinical information only, and VDP but not spirometry was a significant predictor in a model that controlled for prior exacerbations. INTERPRETATION: Our results show that structural and functional MRI measurements in people with CF were associated with future exacerbations, likely because they directly measure underlying structural and functional aspects of disease.