Monitoring disease progression in childhood bronchiectasis.

Associations between peak oxygen uptake, lung function, and bronchiectasis in children with cystic fibrosis in the era of CFTR modulators.

Paediatric bronchiectasis unrelated to CF is a chronic respiratory condition marked by abnormal bronchial dilatation and persistent wet or productive cough, accompanied by recurrent airway infections and inflammation. Though once considered irreversible, evidence shows that early diagnosis and optimised management can halt or even reverse disease progression in children. The condition is increasingly recognised globally, with potentially higher prevalence in indigenous and low-income populations, although prevalence data is sparse. Diagnosis relies on chest CT imaging and clinical symptoms. Causes include post-infectious damage, immunodeficiencies, and genetic disorders such as PCD, but a large proportion have no identifiable aetiology. Clinical evaluation involves detailed history, imaging, and microbiological assessments. Management focuses on airway clearance, treating infections and addressing underlying causes. Early intervention is crucial to prevent long-term complications and improve quality of life. Despite its impact, paediatric bronchiectasis remains underfunded. There is a need for increased awareness, prospective data collection and research to support standardised care protocols to reduce morbidity and healthcare burden. <bold>Cite as:</bold> Unger SA. Bronchiectasis in children. <italic>In:</italic> Chalmers JD, Shoemark A, Aliberti S, eds. Bronchiectasis (ERS Monograph). Sheffield, European Respiratory Society, 2026; pp. 327–341 [<ext-link>https://doi.org/10.1183/2312508X.10002925</ext-link>].

Pleural effusions cause breathlessness, decreased activity levels, and impaired quality of life. Clinical trials of drainage of pleural effusion use patient-reported outcome measures (PROMs) to assess these variables. This systematic review aimed to identify which PROMs have been used in clinical trials in pleural effusions, what variables were assessed, whether they were responsive to pleural interventions, and whether they have been validated in patients with pleural effusions, including a defined minimal clinically important difference (MCID). A systematic review was performed to identify relevant clinical trials from Medline, EMBASE, Emcare, and CINAHL and data were extracted.From 329 abstracts, 29 clinical trials of pleural effusion drainage that used PROMs as an outcome measure were identified. A total of 16 different PROMs were used. The most used PROMs were unidimensional measurements of breathlessness, particularly the visual analogue scale for dyspnoea (VASD), all of which nearly showed improvements in breathlessness following pleural fluid drainage. Other variables commonly assessed included activity levels and health-related quality of life. Multidimensional PROMs showed inconsistent responsiveness to pleural fluid drainage. Only the VASD was validated in this patient group with a defined MCID.A range of PROMs are used in clinical trials of pleural fluid drainage. No single PROM measures all the outcomes of interest. Unidimensional measurements of breathlessness are responsive to pleural fluid drainage. Only the VASD is validated with an MCID. There is a need for properly validated, response PROMs which measure the key outcomes of interest in this patient group.

Improving the Diagnosis and Treatment of Paediatric Bronchiectasis Through Research and Translation

Background: Lung transplantation (LTx) is a life-saving procedure with beneficial effects on health-related quality of life (HRQL) and exercise capacity. Respiratory muscle changes contribute to functional limitations pre-LTx, but their association with post-LTx respiratory symptoms, HRQL, and physical function have not been well characterized. This study aims to: 1) assess differences in respiratory muscle structure and function, HRQL, and physical function in LTx recipients compared to age and sex-matched LTx candidates; 2) evaluate the relationship between respiratory muscle function and post-LTx outcomes. Methods: Prospective, single-center cross-sectional study of adult bilateral LTx recipients (≥ 3 months post-LTx) with prior diagnosis of chronic obstructive pulmonary disease (COPD) or interstitial lung disease (ILD), and pre-LTx participants matched for age, sex, and lung disease. Ultrasound of the diaphragm (M-mode, 5-12 Hz) and sternocleidomastoid (SCM), physical function (handgrip and neck flexion strength, short physical performance battery [SPPB] and six-minute walk distance [6MWD]), respiratory symptoms and HRQL (St. George's Respiratory Questionnaire [SGRQ] and Short-Form 36 [SF-36]) were evaluated. Diaphragm thickening fraction (TF) was measured during normal (TFdi-tidal) and maximal breathing (TFdi-max) with diaphragm force reserve ratio (1-[TFdi-tidal/TFdi-max]) calculated. SCM TF was also measured at maximal inspiration. Results: 30 LTx recipients (64±8 years, 67% ILD, 33% COPD, 67% male; median 9 months post-LTx) and 10 pre-LTx controls (64±5 years, 60% ILD, 40% COPD, 30% male) were evaluated. Post-LTx participants had greater diaphragm function with a lower resting diaphragm TF, greater maximal diaphragm TF, and a higher diaphragm force reserve ratio than pre-LTx participants (Table 1). Results suggest that SCM TF during maximal inspiration may be higher in post-LTx participants (0.60 ± 0.31 vs 0.46 ± 0.24, p=0.15). HRQL, respiratory symptoms, maximal inspiratory pressure (MIP), and 6MWD were better in LTx recipients compared to candidates (Table 1). In LTx recipients, diaphragm force reserve ratio had a strong correlation with lower respiratory symptom severity (SGRQ Symptoms [r=-0.62, p=0.0004]) and greater inspiratory muscle strength (MIP [r=0.38, p=0.04]). SCM TF had a stronger correlation with SGRQ Total Score (r=-0.42, p=0.03), SF-36 PCS (r=0.44, p=0.02), and SPPB (r=0.58, p=0.002), but not 6MWD (r=0.18, p=0.37). Conclusion: Preliminary findings highlight that diaphragm function is greater in LTx recipients than candidates and respiratory muscle function is associated with improved respiratory symptoms and HRQL. However, results should be interpreted with caution due to sex imbalances between groups. This study may guide the implementation of rehabilitation interventions like inspiratory muscle training to enhance outcomes post-LTx.

Cholestatic liver disease causes significant morbidity and mortality in children. The diagnosis and management of these diseases can be complicated by an inability to detect early stages of fibrosis and a lack of adequate interventional therapy. There is no single gold standard test that accurately reflects the presence of liver disease, or that can be used to monitor fibrosis progression, particularly in conditions such as cystic fibrosis. This has lead to controversy over how suspected liver disease in children is detected and diagnosed. This review discusses the challenges in using commonly available methods to diagnose hepatic fibrosis and monitor disease progression in children with cholestatic liver disease. In addition, the review examines the mechanisms hypothesised to be involved in the development of hepatic fibrogenesis in paediatric cholestatic liver injury which may ultimately aid in identifying new modalities to assist in both disease detection and therapeutic intervention.

Transient Elastography in Healthy Children and Children with Cystic Fibrosis

To provide an update on the recent evidence underpinning the approach to nutritional care in patients with severe primary chronic small bowel dysmotility. Patients with severe chronic small intestinal dysmotility suffer nutritional and nonnutritional morbidity, both as a result of their underlying polysymptomatic, poorly understood condition and the interventions required. A proportion require artificial nutrition support; however, this is associated with impaired quality of life and associated complications. The approach to nutritional support must therefore engage a multidisciplinary team (MDT) to ensure that decisions to escalate beyond oral nutrition reflect individualised risk-benefit discussions while adopting a holistic approach to symptom management. Since nutritional outcomes are worse in those with the chronic intestinal pseudo-obstruction (CIPO) phenotype, differentiation into CIPO and non-CIPO subgroups, using a pragmatic diagnostic approach rather than invasive/poorly tolerated investigations, can be an important step in achieving nutritional care tailored to the individual. Malnutrition in patients with severe chronic small intestinal dysmotility is multifactorial. Early engagement of a broad team that includes dietitians, psychologists and pain management experts is crucial to achieving the most beneficial and least harmful patient-centred nutritional care outcomes.

We reported defective efferocytosis associated with cigarette smoking and/or airway inflammation in chronic lung diseases, including chronic obstructive pulmonary disease, severe asthma, and childhood bronchiectasis. We also showed defects in phagocytosis of nontypeable Haemophilus influenzae (NTHi), a common colonizer of the lower airway in these diseases. These defects could be substantially overcome with low-dose azithromycin; however, chronic use may induce bacterial resistance. The aim of the present study was therefore to investigate two novel macrolides-2'-desoxy-9-(S)-erythromycylamine (GS-459755) and azithromycin-based 2'-desoxy molecule (GS-560660)-with significantly diminished antibiotic activity against Staphylococcus aureus, Streptococcus pneumonia, Moraxella catarrhalis, and H. influenzae We tested their effects on efferocytosis, phagocytosis of NTHi, cell viability, receptors involved in recognition of apoptotic cells and/or NTHi (flow cytometry), secreted and cleaved intracellular IL-1β (cytometric bead array, immunofluorescence/confocal microscopy), and nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) using primary alveolar macrophages and THP-1 macrophages ± 10% cigarette smoke extract. Dose-response experiments showed optimal prophagocytic effects of GS-459755 and GS-560660 at concentrations of 0.5-1 µg/ml compared with our findings with azithromycin. Both macrolides significantly improved phagocytosis of apoptotic cells and NTHi (e.g., increases in efferocytosis and phagocytosis of NTHi: GS-459755, 23 and 22.5%, P = 0.043; GS-560660, 23.5 and 22%, P = 0.043, respectively). Macrophage viability remained >85% following 24 h exposure to either macrolide at concentrations up to 20 µg/ml. Secreted and intracellular-cleaved IL-1β was decreased with both macrolides with no significant changes in recognition molecules c-mer proto-oncogene tyrosine kinase; scavenger receptor class A, member 1; Toll-like receptor 2/4; or CD36. Particulate cytoplasmic immunofluorescence of NLRP3 inflammasome was also reduced significantly. We conclude that GS-459755 and GS-560660 may be useful for reducing airway inflammation in chronic lung diseases without inducing bacterial resistance.

ObjectivesData from the German Aortic Valve Registry (GARY) were analysed to determine whether there are differences between patients with and without chronic lung disease (CLD) undergoing transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) and whether TAVI or SAVR is more beneficial in patients with preexisting CLD.MethodsFollow-up data from GARY registry patients treated from 2014 to 2015 and from 2018 to 2019 were incorporated in the analysis. Demographic results for each of the 2 treatment modalities were evaluated, and patients with and without CLD were compared. In a second step, variables that would have influenced the treatment decision in CLD patients in direction of either SAVR or TAVI were accounted for in the adjusted analysis. This led to a subgroup of 1385 patients with CLD that was subjected to propensity score weighted analysis to compare outcomes of TAVI and SAVR.ResultsAfter exclusion, 11 457 SAVR patients and 2378 TAVI patients were analysed. CLD patients were sicker than patients without CLD, although the observed 30-day mortality was lower than expected by 3 risk scores. Accordingly, long-term survival in CLD patients was lower in both treatment groups than in patients without CLD. Thirty-day mortality was similar in the 2 treatment groups (SAVR 2.3%, TAVI 3.8%, P = .964) in spite of a possible selection bias in favour of SAVR. During a 5-year follow-up, survival after TAVI (44.6%) was significantly lower than after SAVR (56.7%), P = .029.ConclusionsPatients with CLD undergoing SAVR or TAVI are generally at higher risk for complications or death after the procedure than patients without CLD. After 5 years, patient-reported outcomes were similar in TAVI and in SAVR patients.

Interstitial lung diseases (ILDs), a group of parenchymal lung disorders, present with varying degrees of inflammation and fibrosis, which lead to symptoms such as progressive breathlessness, impaired quality of life (QoL), and reduced life expectancy. Patients with ILD can experience a sudden worsening of their condition, known as an acute exacerbation, which is associated with inappropriate hospital admissions, concomitant National Health Service (NHS) costs, impaired QoL, and high mortality. The heterogeneity of ILDs, the unpredictability of acute exacerbations, and significant variation in disease progression and response to treatment present numerous management challenges. Standard care typically involves 3-6 monthly hospital outpatient visits to monitor disease and assess response to treatment. Home monitoring with remote review of spirometry, pulse oximetry, and patient-reported measures offers an alternative approach to in-person clinic review and laboratory-based physiological measurements. Clinical trials indicate home monitoring of patients with ILD is acceptable, and results correlate with laboratory-based pulmonary function tests (PFTs). The impact of implementing home monitoring for patients with ILD in a real-world setting is not well understood. We aim to evaluate the safety, effectiveness, and acceptability of home monitoring with standard care in the management of patients with ILD. This study has been registered as a quality improvement project at Guy's and St Thomas' NHS Foundation Trust (reference 13660) and Royal Devon University Healthcare NHS Foundation Trust (reference 24-1378). The project has been co-designed by the steering group, including clinicians, researchers, technology partners, a patient advocacy charity, and patients diagnosed with ILD. Patients who meet the inclusion criteria will be provided a handheld spirometer, pulse oximeter, and access to patientMpower, an electronic health app, on their smart devices and followed up for 12 months. All participants will be asked to complete at least once weekly home spirometry and pulse oximetry measurements and 3 monthly patient-reported measures, including outcome, engagement, and experience measures, using the patientMpower app. Results will be available to the clinicians in real time and used to monitor disease progression, symptoms, and QoL, and to assess treatment response. This study was funded by NHS Digital in September 2021. Patient recruitment and data collection started in March 2022. By January 2024, 186 patients were enrolled. All patients will have home monitoring for at least 12 months. Results are expected to be published at the end of 2025. We hypothesize home monitoring will be safe, effective and acceptable for patients with ILD and result in a 50% reduction in routine laboratory-based pulmonary function tests and in-person clinic consultations. DERR1-10.2196/65339.

• Consensus recommendations for managing chronic suppurative lung disease (CSLD) and bronchiectasis, based on systematic reviews, were developed for Australian and New Zealand children and adults during a multidisciplinary workshop. • The diagnosis of bronchiectasis requires a high-resolution computed tomography scan ofthe chest. People with symptoms of bronchiectasis, but non-diagnostic scans, have CSLD, which may progress to radiological bronchiectasis. • CSLD/bronchiectasis is suspected when chronic wet cough persists beyond 8 weeks. Initial assessment requires specialist expertise. Specialist referral is also required for children who have either two or more episodes of chronic (> 4 weeks) wet cough per year that respond to antibiotics, or chest radiographic abnormalities persisting for at least 6 weeks after appropriate therapy. • Intensive treatment seeks to improve symptom control, reduce frequency of acute pulmonary exacerbations, preserve lung function, and maintain a good quality of life. • Antibiotic selection for acute infective episodes is based on results of lower airway culture, local antibiotic susceptibility patterns, clinical severity and patient tolerance. Patients whose condition does not respond promptly or adequately to oral antibiotics are hospitalised for more intensive treatments, including intravenous antibiotics. • Ongoing treatment requires regular and coordinated primary health care and specialist review, including monitoring for complications and comorbidities. • Chest physiotherapy and regular exercise should be encouraged, nutrition optimised, environmental pollutants (including tobacco smoke) avoided, and vaccines administered according to national immunisation schedules. • Individualised long-term use of oral or nebulised antibiotics, corticosteroids, bronchodilators and mucoactive agents may provide a benefit, but are not recommended routinely.

Chronic obstructive lung disease and respiratory muscle function: The role of nutrition and exercise training in cystic fibrosis

Many preterm infants who survive go on to develop chronic lung disease. This is probably due to persistent inflammation in the lungs. Corticosteroids have powerful anti-inflammatory effects and have been used to treat established chronic lung disease. However, it is unclear whether any beneficial effects outweigh the adverse effects of these drugs. To determine the relative benefits and adverse effects associated with late (> 7 days) postnatal systemic corticosteroid treatment compared with control (placebo or nothing) in the preterm infant with evolving or established chronic lung disease. We sought randomised controlled trials (RCTs) of postnatal corticosteroid therapy from the Cochrane Central Register of Controlled Trials (CENTRAL 2013, Issue 8), MEDLINE (1966 through August 2013), handsearching paediatric and perinatal journals, and by examining previous review articles and information received from practising neonatologists. When possible, we contacted authors of all studies to confirm details of reported follow-up studies or to obtain any information about long-term follow-up where none had been reported. We selected RCTs of postnatal corticosteroid treatment initiated after seven days after birth in preterm infants with evolving or established chronic lung disease for this review. We extracted and analysed data regarding clinical outcomes including mortality, chronic lung disease, death or chronic lung disease, failure to extubate, complications in the primary hospitalisation, and long-term health outcomes Twenty-one RCTs enrolling a total of 1424 participants were eligible for this review. All were randomised controlled trials, but the methods for random allocation were not always clear. Allocation concealment, blinding of the intervention and blinding of the outcome assessments were mostly satisfactory. Late steroid treatment was associated with a reduction in neonatal mortality (at 28 days), but not mortality at discharge or latest reported age. Benefits of delayed steroid treatment included reductions in failure to extubate by three, seven or 28 days, chronic lung disease at both 28 days and 36 weeks' postmenstrual age, need for late rescue treatment with dexamethasone, discharge on home oxygen, and death or chronic lung disease at both 28 days and 36 weeks' postmenstrual age. There was a trend towards an increase in risk of infection and gastrointestinal bleeding, but not necrotising enterocolitis. Short-term adverse affects included hyperglycaemia, glycosuria and hypertension. There was an increase in severe retinopathy of prematurity, but no significant increase in blindness. There was a trend towards a reduction in severe intraventricular haemorrhage, but only 247 infants were enrolled in five studies reporting this outcome. The trends to an increase in cerebral palsy or abnormal neurological examination were partly offset by a trend in the opposite direction in death before late follow-up. The combined rate of death or cerebral palsy was not significantly different between steroid and control groups. Major neurosensory disability, and the combined rate of death or major neurosensory disability, were not significantly different between steroid and control groups. There were no substantial differences between groups for other outcomes in later childhood, including respiratory health or function, blood pressure or growth, although there were fewer with a clinically important reduction in the forced expired volume in one second (FEV1) on respiratory function testing. The benefits of late corticosteroid therapy may not outweigh actual or potential adverse effects. Although there continues to be concern about an increased incidence of adverse neurological outcomes in infants treated with postnatal steroids, this review of postnatal corticosteroid treatment for chronic lung disease initiated after seven days of age suggests that late therapy may reduce neonatal mortality without significantly increasing the risk of adverse long-term neurodevelopmental outcomes. However, the methodological quality of the studies determining the long-term outcome is limited in some cases; in some studies the surviving children have only been assessed before school age, when some important neurological outcomes cannot be determined with certainty, and no study was sufficiently powered to detect increased rates of important adverse long-term neurosensory outcomes. Given the evidence of both benefits and harms of treatment, and the limitations of the evidence at present, it appears prudent to reserve the use of late corticosteroids for infants who cannot be weaned from mechanical ventilation and to minimise the dose and duration of any course of treatment.

Patient-Reported Outcomes (PRO) Data from Patients (Pts) with Essential Thrombocythemia (ET) Enrolled in the MOST Study