European Respiratory Review最新文献

Context: Despite the clinical benefits, the administration of biologics in asthma is not without adverse effects. However, there is a lack of information on the safety profile, particularly in children.

Objective: To provide a systematic review of the range of reported adverse events (AEs) of biologic treatments approved for paediatric asthma (Xolair, Nucala, Dupixent, Fasenra and Tezspire).

Data sources: Databases (MEDLINE, CENTRAL, Scopus and Web of Science) and one registry (ClinicalTrials.gov).

Study selection: This review included randomised clinical trials, prospective clinical studies, real-world studies, exploratory studies, registry analyses, case series and case reports, which met predefined inclusion criteria.

Data extraction: Study characteristics and AEs were extracted into predefined forms and then summarised in terms of their frequency and study duration.

Results: Overall, 45 reports and 13 clinical trials met the inclusion criteria for data evaluation, of which eight studies were placebo-controlled. Overall, paediatric asthma patients' most frequently reported AEs were headache, injection site reactions, upper respiratory tract infections, pyrexia and urticaria. The systematic analysis revealed a similar safety profile of the biologics to that reported on the product labels.

Limitations: The small number of paediatric patients, missing placebo control groups, variant definitions of AEs and a lack of statistical evaluation limited the validation of specific AEs to individual biologics.

Conclusions: In this systematic review, no new safety concerns regarding the use of biologics in paediatric asthma were identified, even after an observation period of up to 7 years. In order to record rare side-effects and possible long-term consequences, further data from paediatric study cohorts are needed.

Dipeptidyl peptidase (DPP)-1 (also known as cathepsin C) inhibitors are the first disease-specific therapy shown to be effective in bronchiectasis. The mechanism of action of DPP-1 inhibitors is suppression of activity of neutrophil serine proteases (NSPs) by preventing them from being activated during neutrophil maturation in the bone marrow. NSPs exert multiple directly damaging effects and contribute to ongoing dysregulated airway inflammation. High airway levels of NSPs are linked to bronchiectasis disease severity. Several phase 2 and one phase 3 trial have now confirmed that DPP-1 inhibitors reduce activity of the NSPs in the airways and have clinical benefits in bronchiectasis including reducing exacerbations and improving other clinical end-points such as quality of life and slowing lung function decline. DPP-1 inhibition may also be a promising treatment avenue in other diseases where neutrophilic inflammation is implicated. Future directions include establishing direct and downstream effects of DPP-1 inhibitors in humans and seeking biomarkers to guide clinical application.

Rationale: Survivors of preterm birth (<37 weeks' gestation) have low peak oxygen uptake, a global measure of aerobic fitness and an established predictor of increased morbidity and mortality. However, little is known about other cardiopulmonary outcome measures in this population. We addressed the hypothesis that preterm birth is associated with abnormal respiratory, cardiovascular and metabolic responses to exercise, as assessed by cardiopulmonary exercise testing, via a systematic review and meta-analysis.

Methods: Six databases were systematically searched up to 29 November 2024 (PROSPERO: CRD42022320775). Studies reporting cardiopulmonary outcome measures obtained during a standardised exercise test were included if they had preterm-born participants and matched term-born controls. The standardised mean difference (SMD) between pooled preterm-born and term-born cohorts was calculated using random-effects models for the meta-analysis.

Results: Of the 12 143 records identified, 47 cohorts were included in the final meta-analysis. At peak exercise, the preterm-born cohort (n=2149) demonstrated lower oxygen uptake (SMD -0.39, 95% CI -0.52 to -0.26), work rate (SMD -0.53, 95% CI -0.70 to -0.35), minute ventilation (SMD -0.43, 95% CI -0.60 to -0.26), tidal volume (SMD -0.38, 95% CI -0.62 to -0.15), oxygen pulse (SMD -0.47, 95% CI -0.75 to -0.19), heart rate (SMD -0.18, 95% CI -0.28 to -0.07), anaerobic threshold (SMD -0.29, 95% CI -0.49 to -0.08) and gas exchange efficiency (SMD 0.22, 95% CI 0.04 to 0.41), compared to the term-born cohort (n=1650).

Conclusions: In addition to a reduced peak oxygen uptake, survivors of preterm birth have impairments in the respiratory, cardiovascular and metabolic domains during cardiopulmonary exercise testing. Given that reduced aerobic capacity is associated with increased morbidity and mortality, exercise interventions that target cardiorespiratory fitness should be prioritised across the lifespan in those born preterm.

Background: The association between long-term ambient air pollution and adult lung function has been inconsistently reported. This systematic review and meta-analysis aimed to quantify the impact of long-term (≥1 year) ambient air pollution on adult lung function.

Methods: Original articles published between 1 January 2006 and 26 July 2024 were searched in PubMed, Embase and Web of Science. Random-effects models were used to assess the strength of associations of gaseous (nitrogen dioxide and ozone) and particulate matter (PM) pollutants with diameters ≤2.5 and 10 µg, with lung function (forced expiratory volume in 1 s (FEV₁), forced vital capacity (FVC) and FEV₁/FVC ratio). Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation system (GRADE) approach.

Results: Of 25 064 potential papers, 27 were included, of which 12 were meta-analysed. There was low-certainty evidence that a 10 µg·m^-3 increase in long-term NO₂ exposure was associated with lower FEV₁ (-15.6 mL, 95% CI -25.0- -6.2; I ²=86%; p<0.01) and high-certainty evidence for FVC (-25.3 mL, 95% CI -36.7- -14.0; I ²=70%, p<0.01). Similar associations were observed for PM_2.5, while long-term exposure to O₃ and PM₁₀ were associated with lower FEV₁ with high- and moderate-certainty evidence, respectively. Exposure to O₃ was associated with lower FEV₁/FVC (high-certainty evidence).

Interpretation: Long-term exposure to ambient air pollution adversely impacts adult lung function. This emphasises the importance of ongoing commitments to mitigating air pollution levels to preserve optimum lung health and prevent premature lung function decline that can lead to earlier and avoidable respiratory diseases.

Objective: To assess the effect of obesity on the prevalence of asthma, obstetric outcomes and delivery outcomes in pregnant women with asthma.

Methods: A comprehensive systematic review and meta-analysis were conducted up to 31 March 2024, using four public search engines. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, both quantitative and qualitative data were collected and analysed.

Results: We included 11 studies from 2006 to 2022 involving 77 611 386 pregnant patients (3.1% had asthma). Obesity increased the odds of asthma (n=2; OR 2.42, 95% CI 1.14-5.15) and increased that of uncontrolled asthma (n=6; OR 1.29, 95% CI 1.11-1.50) in pregnant women. In an adjusted pooled analysis, pregnant women with asthma were more likely to develop hypertensive disorders of pregnancy (HDP) (n=3; adjusted OR (aOR) 1.21, 95% CI 1.10-1.34), gestational diabetes mellitus (GDM) (n=3; aOR 1.14, 95% CI 1.04-1.26), fetal growth restriction (FGR) (n=2; aOR 1.18, 95% CI 1.15-1.21), preterm birth (PTB) (n=2; aOR 1.26, 95% CI 1.25-1.27), caesarean delivery (CD) (n=3; aOR 1.22, 95% CI 1.11-1.33) and severe maternal morbidity (n=1; aOR 1.50, 95% CI 1.45-1.55). Three comparator studies that examined the effect of obesity on obstetric outcomes cited obesity as a risk factor for HDP (n=1; aOR 1.7, 95% CI 1.3-2.3), GDM (n=1; aOR 4.2, 95% CI 2.8-6.3) and CD (n=1; aOR 1.6, 95% CI 1.3-2.0) in pregnant women with asthma.

Conclusions: Pregnancy with asthma may increase the risk of HDP, GDM, FGR, PTB and CD, and obesity has the potential to further increase the risk of HDP, GDM and CD in pregnant women with asthma.

Background: In fibrotic hypersensitivity pneumonitis (fHP) an ongoing immune response triggers pulmonary inflammation and concurrent fibrotic pathways, leading to irreversible disease progression. Patients with the progressive pulmonary fibrosis (PPF) phenotype have a poor prognosis. Reliable identification of biomarkers to predict PPF could aid clinicians in determining disease prognosis and optimising patient care. We aimed to identify prognostic biomarkers for the PPF phenotype in fHP using existing literature.

Methods: We performed a systematic review (PROSPERO, CRD42024537599) and searched Medline, Embase and Scopus from inception to 10 April 2024. We included studies that evaluated the ability of biomarkers measured in blood or bronchoalveolar lavage fluid (BALF) to predict disease progression in adult patients with fHP. Study quality was assessed using the Quality Assessment of Prognostic Accuracy Studies tool.

Results: Of the 3027 articles initially identified, 31 met the inclusion criteria, encompassing a total of 3766 fHP patients. 65 biomarkers were identified; however, most were evaluated in only one (n=49) or two (n=6) studies. The most frequently evaluated biomarkers were BALF cellular composition, serum Krebs von den Lungen-6 and serum surfactant protein D levels. Survival was the most commonly assessed outcome, followed by disease progression and acute exacerbation. None of the biomarkers reliably predicted the prognosis.

Conclusions: A large number of biomarkers have been evaluated for their prognostic ability in fHP, but none of them appear to be consistently associated with the PPF phenotype. Heterogeneity across studies in terms of methods, disease definitions, outcomes and measurement time points complicates the identification of a marker with strong potential, and this situation should be improved in the clinical field.

As survival rates of preterm infants have increased due to advances in perinatal care, focus has shifted towards the profound long-term effects of prematurity. An extensive amount of evidence has shown increased susceptibility to chronic illnesses among preterm infants. While the onset of such conditions typically emerges during adulthood, their roots trace back to the early stages of life. Much of this interest has been directed towards short- and long-term consequences of extreme and very preterm birth. However, it has become apparent that, despite a limited risk of complications during the neonatal period, the moderate and late preterm population suffers from an increased likelihood of morbidity during the course of life. Considering the higher prevalence of moderate and late preterm births compared to extreme and very preterm births, understanding and investigating their health outcomes is essential to address the broader impact of prematurity. In this review, we will discuss the impact of moderate and late prematurity on lung development, function and how environmental factors impose these individuals to increased risk for respiratory morbidity during the course of life. We describe interventions during early life that may protect the moderate-to-late preterm population from adverse lung development and further deterioration by addressing modifiable risk factors.

Background: Innovation in ultrasound technology has led to the development of portable devices which can transmit images in real time to a remotely located expert, known as live teleultrasound. This allows immediate feedback on image acquisition, assistance with interpretation and subsequent clinical decision-making.

Aim: We performed a systematic review of the literature to examine outcomes related to live teleultrasound of the chest.

Methods: A systematic search for studies reporting outcomes from live teleultrasound of the chest (excluding cardiac) in adults was performed in PubMed, MEDLINE, Embase, CINAHL and Cochrane CENTRAL. At least two independent reviewers were involved in screening, data extraction and critical appraisal.

Results: In total, 1855 eligible studies were identified. Of those, 106 studies progressed to full-text screening and 43 studies were included for data extraction. Case reports and feasibility studies were most prevalent, and study quality was low overall. Commonly reported outcomes included 1) image quality rated by a remote clinician; 2) remote clinician's comfort in making management decisions; and 3) comparison of teleultrasound image acquisition with images acquired at the bedside by an expert. Three diagnostic accuracy studies demonstrated a high accuracy of teleultrasound for the identification of signs such as lung sliding, the interstitial syndrome and pleural effusion. Consolidation was less reliably identified. Eight studies collected qualitative data on attitudes of remote and face-to-face clinicians, which were consistently positive.

Conclusion: Low-quality evidence suggests that live teleultrasound can be used to assess the lungs and pleural space; however, further study is required to ensure its diagnostic accuracy.

Importance: The minimum important difference (MID) for field walking tests aims to improve interpretation of outcomes, but the volume and heterogeneity of MIDs for these tests is challenging. We aimed to determine the MID for the 6-min walk distance (6MWD), incremental shuttle walk test (ISWT) and endurance shuttle walk test (ESWT) in adults with long-term conditions.

Methods: This systematic review included studies that generated a MID using an anchor-based approach in patients with long-term conditions for the 6MWD, ISWT or ESWT field walking tests. Studies were screened and data extracted by independent reviewers. Meta-analyses were performed using RevMan.

Results: 42 studies were included in the analyses, involving n=13 949 participants. Of these, 12 studies involving exercise as an intervention were included in the meta-analyses to produce MIDs, presented as mean (95% confidence interval). The MID for the 6MWD was 25 m (24-26 m) for respiratory conditions, 23 m (8-37 m) for cardiac conditions and 37 m (26-49 m) for neurological/musculoskeletal conditions. The MID for the ISWT was 48 m (39-57 m) for respiratory conditions and 70 m (55-85 m) for cardiac conditions. The MID for ESWT in COPD was 159 s (94-224 s). The pooled MID across conditions within exercise interventions was 26 m (22-40 m) for the 6MWD and 53 m (44-62 m) for the ISWT, with reasonable heterogeneity (I²=48% and I²=47%, respectively).

Conclusion: We propose new MIDs for exercise interventions using anchor-based methodology in long‑term conditions for the 6MWD, ISWT and ESWT. These can be used internationally for meta‑analyses where studies have used different field walking tests, to optimise trial sample size calculations, and for clinical service benchmarking.

Background: Artificial intelligence (AI) systems have been implemented to improve the diagnostic yield and operators' skills within endoscopy. Similar AI systems are now emerging in bronchoscopy. Our objective was to identify and describe AI systems in bronchoscopy.

Methods: A systematic review was performed using MEDLINE, Embase and Scopus databases, focusing on two terms: bronchoscopy and AI. All studies had to evaluate their AI against human ratings. The methodological quality of each study was assessed using the Medical Education Research Study Quality Instrument (MERSQI).

Results: 1196 studies were identified, with 20 passing the eligibility criteria. The studies could be divided into three categories: nine studies in airway anatomy and navigation, seven studies in computer-aided detection and classification of nodules in endobronchial ultrasound, and four studies in rapid on-site evaluation. 16 were assessment studies, with 12 showing equal performance and four showing superior performance of AI compared with human ratings. Four studies within airway anatomy implemented their AI, all favouring AI guidance to no AI guidance. The methodological quality of the studies was moderate (mean MERSQI 12.9 points, out of a maximum 18 points).

Interpretation: 20 studies developed AI systems, with only four examining the implementation of their AI. The four studies were all within airway navigation and favoured AI to no AI in a simulated setting. Future implementation studies are warranted to test for the clinical effect of AI systems within bronchoscopy.