European Respiratory Review最新文献

Background: Immature lung development and respiratory morbidity place preterm-born children at high risk of long-term pulmonary sequelae. This systematic review and meta-analysis aims to quantify lung function in preterm-born children and identify risk factors for a compromised lung function.

Methods: We searched MEDLINE, Embase, Cochrane Library, Web of Science and Scopus for relevant studies published on preterm cohorts born since 1990. Studies comparing forced expiratory volume in 1 s (FEV₁) in preterm-born children aged ≥5 years to term-born controls or normative data were included. Study quality was assessed using the Newcastle-Ottawa Scale for cohort studies. Standardised mean differences in FEV₁ and secondary spirometry outcomes per study were pooled using meta-analysis. The impact of different demographic and neonatal variables on studies' FEV₁ effect sizes was investigated by meta-regression analyses. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations framework.

Results: We identified 42 studies with unique cohorts including 4743 preterm children and 9843 controls. Median gestational age in the studies was 28.0 weeks and age at assessment ranged from 6.7 to 16.7 years. Preterm children had lower FEV₁ than controls (-0.58 sd, 95% CI -0.69- -0.47 sd, p<0.001) resulting in a relative risk of 2.9 (95% CI 2.4-3.4) for abnormal outcome, with high certainty of evidence. FEV₁ was significantly associated with gestational age, birthweight, bronchopulmonary dysplasia and invasive mechanical ventilation in univariate meta-regression analyses (R²=36-96%).

Conclusion: This systematic review shows robust evidence of impaired lung function in preterm-born children with a high certainty of evidence.

Background: Severe asthma significantly impacts a minority of children with asthma, leading to frequent symptoms, hospitalisations and potential long-term health consequences. However, accurate global data on severe asthma epidemiology is lacking. This study aims to address this gap, providing data on severe asthma epidemiology, regional differences and associated comorbidities.

Methods: We conducted a rigorous systematic review and meta-analysis following a registered protocol (PROSPERO CRD42023472845). We searched PubMed, Scopus and Web of Science for cohort or cross-sectional studies published since 2003, evaluating severe asthma incidence and prevalence in children. Study quality and risk of bias were assessed using STROBE guidelines.

Results: Nine studies investigating European children with asthma (aged 5-18 years) were included in the meta-analysis. No significant publication bias was found. The overall severe asthma prevalence in children with asthma was 3% (95% CI 1-6; I²=99.9%; p<0.001), with no significant difference between males and females. Prevalence estimates varied significantly depending on the diagnostic criteria used (Global Initiative for Asthma: 6%; European Respiratory Society/American Thoracic Society: 1%; other: 3%). Because none of the examined studies were prospectively designed, incidence rates could not be determined.

Conclusions: This systematic review and meta-analysis provide the first robust assessment of severe asthma prevalence among European children. Our findings underscore the need for comprehensive research to address knowledge gaps in severe asthma, including determining incidence rates, standardising definitions, investigating regional differences and evaluating comorbidities and treatment strategies.

Background: Several genetic variants are associated with the risk of idiopathic pulmonary fibrosis (IPF). These have not been systematically reviewed.

Methods: We searched the PubMed, Embase and GWAS Catalog databases for studies indexed between inception and 15 January 2024 describing genetic variants associated with IPF susceptibility. We included studies describing common associated single nucleotide polymorphisms (SNPs). We excluded studies describing rare variants, non-SNP variants and those without an allelic model analysis. We recorded study type, participant characteristics, genotyping methods, IPF diagnostic criteria, the SNPs and the respective genes, odds ratios, and other details. We also searched databases for functions of the identified genes.

Results: The primary search retrieved 2697 publications; we included 42 studies. There were nine genome-wide association/linkage studies, while 27 were candidate gene studies. The studies included 22-11 160 IPF subjects. 88 SNPs in 58 genes or loci were found associated with IPF susceptibility. MUC5B rs35705950 was the most studied SNP. Most (n=51) SNPs were in the intronic or intergenic regions; only 11 were coding sequence variants. The SNPs had odds ratios ranging from 0.27 to 7.82 for an association with IPF. Only 22 SNPs had moderate-large effects (OR >1.5 or <0.67). Only 49.1% of the associated genes have a known functional role in IPF; the role of G protein-related signalling and transcriptional regulation (zinc-finger proteins) remain unexplored.

Conclusion: Several common SNPs in over 50 genes have been found associated with IPF susceptibility. These variants may inform gene panels for future studies (PROSPERO CRD42023408912).

Cystic fibrosis (CF) is a genetic disease caused by variants in the gene encoding for the CF transmembrane conductance regulator (CFTR) protein, a chloride and bicarbonate channel. CFTR dysfunction results in a multiorgan disease with the main clinical features being exocrine pancreatic insufficiency and diffuse bronchiectasis with chronic airway infection leading to respiratory failure and premature death. Over the past decades, major progress has been made by implementing multidisciplinary care, including nutritional support, airway clearance techniques and antibiotics in specialised CF centres. The past decade has further seen the progressive development of oral medications, called CFTR modulators, for which around 80% of people with CF are genetically eligible in Europe. CFTR modulators partially restore ion transport and lead to a rapid and major improvement in clinical manifestations and lung function, presumably resulting in longer survival. CFTR modulators have been game-changing in the care of people with CF. However, many questions remain unanswered, such as the long-term effects of CFTR modulators, especially when treatment is started very early in life, or the new CF-related disease emerging due to CFTR modulators. Moreover, severe complications of CF, such as diabetes or cirrhosis, are not reversed on CFTR modulators and around 20% of people with CF bear CFTR variants leading to a CFTR protein that is unresponsive to CFTR modulators. Challenges also arise in adapting CF care to a changing disease. In this review article, we highlight the new questions and challenges emerging from this revolution in CF care.

Recent bronchiectasis studies from large-scale multinational, multicentre registries have demonstrated that the characteristics of the disease vary according to geographic region. However, most perspectives on bronchiectasis are dominated by data from Western countries. This review intends to provide an Asian perspective on the disease, focusing on the established registries in India, Korea and China. Asian patients with bronchiectasis are less likely to show female predominance and experience exacerbations, are more likely to be younger, have milder disease, and have fewer options for guideline-recommended treatment than those living in other global regions. Furthermore, Asian bronchiectasis patients demonstrate different comorbidities, microbiological profiles and unique endophenotypes, including post-tuberculosis and dry bronchiectasis. Notably, each Asian region reveals further geographic variations and inter-patient differences. Future studies are warranted to better characterise Asian patients with bronchiectasis.

Digital medicine is already well established in respiratory medicine through remote monitoring digital devices which are used in the day-to-day care of patients with asthma, COPD and sleep disorders. Image recognition software, deployed in thoracic radiology for many applications including lung cancer screening, is another application of digital medicine. Used as clinical decision support, this software will soon become part of day-to-day practice once concerns regarding generalisability have been addressed. Embodied in the electronic health record, digital medicine also plays a substantial role in the day-to-day clinical practice of respiratory medicine. Given the considerable work the electronic health record demands from clinicians, the next tangible impact of digital medicine may be artificial intelligence that aids administration, makes record keeping easier and facilitates better digital communication with patients. Future promises of digital medicine are based on their potential to analyse and characterise the large amounts of digital clinical data that are collected in routine care. Offering the potential to predict outcomes and personalise therapy, there is much to be excited by in this new epoch of innovation. However, these digital tools are by no means a silver bullet. It remains uncertain whether, let alone when, the promises of better models of personalisation and prediction will translate into clinically meaningful and cost-effective products for clinicians.

Pulmonary mucociliary clearance (MCC) is an important defence mechanism of the respiratory system and clears pathogens and foreign particles from the airways. Understanding the effect of disease states, drugs, toxins and airway manipulations on MCC could be beneficial in preventing early pulmonary disease and developing new pulmonary therapeutics. This review summarises the current methods and future efforts to detect pulmonary MCC in vivo.

Acute chest syndrome (ACS) is a leading cause of respiratory distress and hospitalisation in children with sickle cell disease (SCD). The aetiology is multifactorial and includes fat embolism, venous thromboembolism, alveolar hypoventilation and respiratory infections, with the latter being particularly common in children. These triggers contribute to a vicious cycle of erythrocyte sickling, adhesion to the endothelium, haemolysis, vaso-occlusion and ventilation–perfusion mismatch in the lungs, resulting in the clinical manifestations of ACS. The clinical presentation includes fever, chest pain, dyspnoea, cough, wheeze and hypoxia, accompanied by a new pulmonary infiltrate on chest radiography. Respiratory symptoms may overlap with those of acute asthma, which may be difficult to distinguish. Patients with ACS may deteriorate rapidly; thus prevention, early recognition and aggressive, multidisciplinary team management is essential. In this narrative review, we highlight the current evidence regarding the epidemiology, pathophysiology, treatment and preventative strategies for ACS, focusing on the aspects of major interest for the paediatric pulmonologist and multidisciplinary team who manage children with SCD.