ERJ Open Research最新文献

[This corrects the article DOI: 10.1183/23120541.00821-2023.].

Introduction: Understanding the interplay of immune mediators in relation to clinical outcomes during acute infection has the potential to highlight immune networks critical to symptom recovery. The objective of the present study was to elucidate the immune networks critical to early symptom resolution following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Methods: In a community-based randomised clinical trial comparing inhaled budesonide against usual care in 139 participants with early onset SARS-CoV-2 (the STOIC study; clinicaltrials.gov identifier NCT04416399), significant clinical deterioration (reported need for urgent care, emergency department visit, hospitalisation: the primary outcome), self-reported symptom severity (Influenza Patient-Reported Outcome questionnaire) and immune mediator networks were assessed. Immune mediator networks were determined using pre-defined mathematical modelling of immune mediators, determined by the Meso Scale Discovery U-Plex platform, within the first 7 days of SARS-CoV-2 infection compared to 22 healthy controls.

Results: Interferon- and chemokine-dominant networks were associated with high viral burden. Elevated levels of the mucosal network (chemokine (C-C motif) ligand (CCL)13, CCL17, interleukin (IL)-33, IL-5, IL-4, CCL26, IL-2, IL-12 and granulocyte-macrophage colony-stimulating factor) was associated with a mean 3.7-day quicker recovery time, with no primary outcome events, irrespective of treatment arm. This mucosal network was associated with initial nasal and throat symptoms at day 0.

Conclusion: A nasal immune network is critical to accelerated recovery and improved patient outcomes in community-acquired viral infections. Overall, early prognostication and treatments aimed at inducing epithelial responses may prove clinically beneficial in enhancing early host response to virus.

Lung function and its mediation role on environmental pollution and mortality https://bit.ly/3pdVYJX.

Background: Air pollution is associated with lower lung function, and both are associated with premature mortality and cardiovascular disease (CVD). Evidence remains scarce on the potential mediating effect of impaired lung function on the association between air pollution and mortality or CVD.

Methods: We used data from UK Biobank (n∼200 000 individuals) with 8-year follow-up to mortality and incident CVD. Exposures to particulate matter <10 µm (PM₁₀), particulate matter <2.5 µm (PM_2.5) and nitrogen dioxide (NO₂) were assessed by land-use regression modelling. Lung function (forced expiratory volume in 1 s (FEV₁), forced vital capacity (FVC) and the FEV₁/FVC ratio) was measured between 2006 and 2010 and transformed to Global Lung Function Initiative (GLI) z-scores. Adjusted Cox proportional hazards and causal proportional hazards mediation analysis models were fitted, stratified by smoking status.

Results: Lower FEV₁ and FVC were associated with all-cause and CVD mortality, and incident CVD, with larger estimates in ever- than never-smokers (all-cause mortality hazard ratio per FEV₁ GLI z-score decrease 1.29 (95% CI 1.24-1.34) for ever-smokers and 1.16 (95% CI 1.12-1.21) for never-smokers). Long-term exposure to PM_2.5 or NO₂ was associated with incident CVD, with similar effect sizes for ever- and never-smokers. Mediated proportions of the air pollution-all-cause mortality estimates driven by FEV₁ were 18% (95% CI 2-33%) for PM_2.5 and 27% (95% CI 3-51%) for NO₂. Corresponding mediated proportions for incident CVD were 9% (95% CI 4-13%) for PM_2.5 and 16% (95% CI 6-25%) for NO₂.

Conclusions: Lung function may mediate a modest proportion of associations between air pollution and mortality and CVD outcomes. Results likely reflect the extent of either shared mechanisms or direct effects relating to lower lung function caused by air pollution.

Background: The management of COPD has been based on the premise of identifying problems that guide personalised treatment based on a multidimensional assessment, known as treatable traits. Exacerbation of COPD (ECOPD) results in physical and functional impairments, limitation of daily activities and negative impact on patients' quality of life and prognosis. In this context, identifying treatable traits in patients with ECOPD is essential to properly guide individualised patient care. There is a need to develop a performance-based toolkit to identify the main treatable traits of functioning in hospitalised patients with ECOPD.

Methods and analysis: This is a study protocol of a survey method observational study to develop a performance-based toolkit. The study will include the following steps: 1) definition of treatable traits by both physiotherapists who provide or have provided care to hospitalised patients with ECOPD on a regular basis, and patients who have experienced at least one ECOPD which required hospitalisation; 2) selection of the most appropriate measures (markers) for each treatable trait based on established criteria and a previous systematic review; and 3) implementation of the toolkit in a pilot/feasibility study with hospitalised patients with ECOPD.

Conclusion: The development of a feasible performance-based toolkit with the best markers for each key treatable trait of functioning in hospitalised patients with ECOPD will make it possible to create individualised patient care for the specific demands of these patients.

Introduction: Readmission following bronchiectasis exacerbation is a common and challenging clinical problem and few simple predictive tools exist. The COPD Assessment Test (CAT) is an easy-to-use questionnaire. This study aims to evaluate the predictive value of CAT scores in determining the risk of readmission in patients with bronchiectasis exacerbation.

Methods: We conducted a prospective cohort study in 106 bronchiectasis patients admitted with exacerbation. All patients completed the CAT at admission and at discharge. Patients were followed-up for 12 months to collect data on readmission. The area under the curve was used to measure the predictive value of CAT at admission, CAT at discharge and change in CAT for readmission due to bronchiectasis exacerbation.

Results: 46 patients were readmitted for bronchiectasis exacerbation within 12 months. High CAT at admission was an independent risk factor for readmission within 12 months in patients with acute exacerbation of bronchiectasis (hazard ratio 3.201, 95% CI 1.065-9.624; p<0.038) after adjustment for confounding variables. The cut-off value of CAT at admission and CAT at discharge to predict 12-month readmission in patients with acute exacerbation of bronchiectasis was 23.5 (sensitivity 62.2%, specificity 83.6%) and 15.5 (sensitivity 52.2%, specificity 87.0%).

Conclusions: CAT at admission is a strong predictor of readmission in patients with bronchiectasis exacerbation.

There was no learning effect found on 6-min walk distance (6MWD) in patients with long COVID, performing a 6-min walk test twice. However, considerable variation in the difference between the two 6MWDs was observed: only 51% showed an increase. https://bit.ly/3H70G1r.

It takes ∼3.5 years to reach a diagnosis of bronchiectasis from onset of symptoms: the long patient's journey in Italy https://bit.ly/46XMWAz.

Background: The effectiveness of using a spray nozzle to deliver lidocaine for superior topical airway anaesthesia during non-sedation flexible bronchoscopy (FB) remains a topic of uncertainty when compared with conventional methods.

Methods: Patients referred for FB were randomly assigned to receive topical lidocaine anaesthesia via the bronchoscope's working channel (classical spray (CS) group) or through a washing pipe equipped with a spray nozzle (SN group). The primary outcome was cough rate, defined as the total number of coughs per minute. Secondary outcomes included subjective perceptions of both the patient and operator regarding the FB process. These perceptions were rated on a visual analogue scale, with numerical ratings ranging from 0 to 10.

Results: Our study enrolled a total of 126 (61 CS group; 65 SN group) patients. The SN group exhibited a significantly lower median cough rate compared with the CS group (4.5 versus 7.1 counts·min^-1; p=0.021). Patients in the SN group also reported less oropharyngeal discomfort (4.5±2.7 versus 5.6±2.9; p=0.039), better tolerance of the procedure (6.8±2.2 versus 5.7±2.7; p=0.011) and a greater willingness to undergo a repeat FB procedure (7.2±2.7 versus 5.8±3.4; p=0.015) compared with those in the CS group. From the operator's perspective, patient discomfort (2.7±1.7 versus 3.4±2.3; p=0.040) and cough scores (2.3±1.5 versus 3.2±2.4; p=0.013) were lower in the SN group compared with the CS group, with less disruption due to coughing observed among those in the SN group (1.6±1.4 versus 2.3±2.3; p=0.029).

Conclusions: This study illustrates that employing a spray nozzle for the delivery of lidocaine provides superior topical airway anaesthesia during non-sedation FB compared with the traditional method.

Introduction: Sulforaphane can induce the transcription factor, Nrf2, promoting antioxidant and anti-inflammatory responses. In this study, hospitalised patients with community-acquired pneumonia (CAP) were treated with stabilised synthetic sulforaphane (SFX-01) to evaluate impact on clinical status and inflammation.

Methods: Double-blind, randomised, placebo-controlled trial of SFX-01 (300 mg oral capsule, once daily for 14 days) conducted in Dundee, UK, between November 2020 and May 2021. Patients had radiologically confirmed CAP and CURB-65 (confusion, urea >7 mmol·L^-1, respiratory rate ≥30 breaths·min^-1, blood pressure <90 mmHg (systolic) or ≤60 mmHg (diastolic), age ≥65 years) score ≥1. The primary outcome was the seven-point World Health Organization clinical status scale at day 15. Secondary outcomes included time to clinical improvement, length of stay and mortality. Effects on Nrf2 activity and inflammation were evaluated on days 1, 8 and 15 by measurement of 45 serum cytokines and mRNA sequencing of peripheral blood leukocytes.

Results: The trial was terminated prematurely due to futility with 133 patients enrolled. 65 patients were randomised to SFX-01 treatment and 68 patients to placebo. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was the cause of CAP in 103 (77%) cases. SFX-01 treatment did not improve clinical status at day 15 (adjusted OR 0.87, 95% CI 0.41-1.83; p=0.71), time to clinical improvement (adjusted hazard ratio (aHR) 1.02, 95% CI 0.70-1.49), length of stay (aHR 0.84, 95% CI 0.56-1.26) or 28-day mortality (aHR 1.45, 95% CI 0.67-3.16). The expression of Nrf2 targets and pro-inflammatory genes, including interleukin (IL)-6, IL-1β and tumour necrosis factor-α, was not significantly changed by SFX-01 treatment. At days 8 and 15, respectively, 310 and 42 significant differentially expressed genes were identified between groups (false discovery rate adjusted p<0.05, log₂FC >1).

Conclusion: SFX-01 treatment did not improve clinical status or modulate key Nrf2 targets in patients with CAP primarily due to SARS-CoV-2 infection.