Necrotizing Pneumonia In Children: A Review.

The objective of the review was to determine the long-term outcomes of necrotising pneumonia (NP). Studies published since 1990 in English, Portuguese, or Spanish, published on PubMed and Scielo were evaluated. Our findings showed ultrasound scanning is the diagnostic modality of choice. Despite prolonged hospitalisation (median 13-27 days) and fever (median 9-16 days), most patients recover completely. Empyema and bronchopleural fistulae are frequent in bacterial NP. Streptococcus pneumoniae is the most prevalent cause. Seventeen studies with 497 patients followed for 30 days to 8.75 years showed that most patients were clinically asymptomatic and had normal lung function. X-ray or CT chest imaging demonstrated that almost all lung lesions recovered within 4-6 months. We suggest that it is not necessary to request frequent chest X-rays during the treatment and recovery process. Chest CT scans should be reserved for specific cases not following the expected clinical course.

START CARE: a protocol for a randomised controlled trial of step-wise budesonide-formoterol reliever-based treatment in children.

Background: Asthma is the most common chronic childhood respiratory condition globally. Inhaled corticosteroid (ICS)-formoterol reliever-based regimens reduce the risk of asthma exacerbations compared with conventional short-acting ß2-agonist (SABA) reliever-based regimens in adults and adolescents. The current limited evidence for anti-inflammatory reliever therapy in children means it is unknown whether these findings are also applicable to children. High-quality randomised controlled trials (RCTs) are needed. Objective: The study aim is to determine the efficacy and safety of budesonide-formoterol reliever alone or maintenance and reliever therapy (MART) compared with standard therapy: budesonide or budesonide-formoterol maintenance, both with terbutaline reliever, in children aged 5 to 11 years with mild, moderate and severe asthma. Methods: A 52-week, multicentre, open-label, parallel group, phase III, two-sided superiority RCT will recruit 400 children aged 5 to 11 years with asthma. Participants will be randomised 1:1 to either budesonide-formoterol 100/6 µg Turbuhaler reliever alone or MART; or budesonide or budesonide-formoterol Turbuhaler maintenance, with terbutaline Turbuhaler reliever. The primary outcome is moderate and severe asthma exacerbations as rate per participant per year. Secondary outcomes are asthma control, lung function, exhaled nitric oxide and treatment step change. Assessment of Turbuhaler technique and cost-effectiveness analysis are also planned. Conclusion: This will be the first RCT to compare the efficacy and safety of a step-wise budesonide-formoterol reliever alone or MART regimen with conventional inhaled ICS or ICS-long-acting ß-agonist maintenance plus SABA reliever in children. The results will provide a much-needed evidence base for the treatment of asthma in children.

Exhaled Volatile Organic Compounds for Asthma Control Classification in Children with Moderate to Severe Asthma: Results from the SysPharmPediA Study.

RATIONALE: Early identification of children with poorly controlled asthma is imperative for optimizing treatment strategies. The analysis of exhaled volatile organic compounds (VOCs) is an emerging approach to identify prognostic and diagnostic biomarkers in pediatric asthma. OBJECTIVES: To assess the accuracy of gas chromatography-mass spectrometry based exhaled metabolite analysis to differentiate between controlled and uncontrolled pediatric asthma. METHODS: This study encompassed a discovery (SysPharmPediA) and validation phase (U-BIOPRED, PANDA). Firstly, exhaled VOCs that discriminated asthma control levels were identified. Subsequently, outcomes were validated in two independent cohorts. Patients were classified as controlled or uncontrolled, based on asthma control test scores and number of severe attacks in the past year. Additionally, potential of VOCs in predicting two or more future severe asthma attacks in SysPharmPediA was evaluated. MEASUREMENTS AND MAIN RESULTS: Complete data were available for 196 children (SysPharmPediA=100, U-BIOPRED=49, PANDA=47). In SysPharmPediA, after randomly splitting the population into training (n=51) and test sets (n=49), three compounds (acetophenone, ethylbenzene, and styrene) distinguished between uncontrolled and controlled asthmatics. The area under the receiver operating characteristic curve (AUROCC) for training and test sets were respectively: 0.83 (95% CI: 0.65-1.00) and 0.77 (95% CI: 0.58-0.96). Combinations of these VOCs resulted in AUROCCs of 0.74 ±0.06 (UBIOPRED) and 0.68 ±0.05 (PANDA). Attacks prediction tests, resulted in AUROCCs of 0.71 (95% CI 0.51-0.91) and 0.71 (95% CI 0.52-0.90) for training and test sets. CONCLUSIONS: Exhaled metabolites analysis might enable asthma control classification in children. This should stimulate further development of exhaled metabolites-based point-of-care tests in asthma.

Post-tuberculosis respiratory impairment in Gambian children and adolescents: A cross-sectional analysis.

BACKGROUND: Although post-tuberculosis lung disease (PTLD) is a known consequence of pulmonary tuberculosis (pTB), few studies have reported the prevalence and spectrum of PTLD in children and adolescents. METHODS: Children and adolescent (≤19 years) survivors of pTB in the Western Regions of The Gambia underwent a respiratory symptom screening, chest X-ray (CXR) and spirometry at TB treatment completion. Variables associated with lung function impairment were identified through logistic regression models. RESULTS: Between March 2022 and July 2023, 79 participants were recruited. The median age was 15.6 years (IQR: 11.8, 17.9); the majority, 53/79 (67.1%), were treated for bacteriologically confirmed pTB, and 8/79 (10.1%) were children and adolescents living with HIV. At pTB treatment completion, 28/79 (35.4%) reported respiratory symptoms, 37/78 (47.4%) had radiological sequelae, and 45/79 (57.0%) had abnormal spirometry. The most common respiratory sequelae were cough (21/79, 26.6%), fibrosis on CXR (22/78, 28.2%), and restrictive spirometry (41/79, 51.9%). Age at TB diagnosis over ten years, undernutrition and fibrosis on CXR at treatment completion were significantly associated with abnormal spirometry (p = .050, .004, and .038, respectively). CONCLUSION: Chronic respiratory symptoms, abnormal CXR, and impaired lung function are common and under-reported consequences of pTB in children and adolescents. Post-TB evaluation and monitoring may be necessary to improve patient outcomes.

Social determinants of respiratory health from birth: still of concern in the 21st century?

Respiratory symptoms are ubiquitous in children and, even though they may be the harbinger of poor long-term outcomes, are often trivialised. Adverse exposures pre-conception, antenatally and in early childhood have lifetime impacts on respiratory health. For the most part, lung function tracks from the pre-school years at least into late middle age, and airflow obstruction is associated not merely with poor respiratory outcomes but also early all-cause morbidity and mortality. Much would be preventable if social determinants of adverse outcomes were to be addressed. This review presents the perspectives of paediatricians from many different contexts, both high and low income, including Europe, the Americas, Australasia, India, Africa and China. It should be noted that there are islands of poverty within even the highest income settings and, conversely, opulent areas in even the most deprived countries. The heaviest burden of any adverse effects falls on those of the lowest socioeconomic status. Themes include passive exposure to tobacco smoke and indoor and outdoor pollution, across the entire developmental course, and lack of access even to simple affordable medications, let alone the new biologicals. Commonly, disease outcomes are worse in resource-poor areas. Both within and between countries there are avoidable gross disparities in outcomes. Climate change is also bearing down hardest on the poorest children. This review highlights the need for vigorous advocacy for children to improve lifelong health. It also highlights that there are ongoing culturally sensitive interventions to address social determinants of disease which are already benefiting children.

Home sleep studies in children with neurodisabilities: success rates and parental perception.

Home sleep studies in children with neurodisabilities have a high success rate (85.4% in our cohort), particularly in patients with limited mobility, have the advantage of reducing the burden of hospital admissions and are the family preferred option https://bit.ly/46t8aWN.

Lung-function trajectories: relevance and implementation in clinical practice.

Lung development starts in utero and continues during childhood through to adolescence, reaching its peak in early adulthood. This growth is followed by gradual decline due to physiological lung ageing. Lung-function development can be altered by several host and environmental factors during the life course. As a result, a range of lung-function trajectories exist in the population. Below average trajectories are associated with respiratory, cardiovascular, metabolic, and mental health comorbidities, as well as with premature death. This Review presents progressive research into lung-function trajectories and assists the implementation of this knowledge in clinical practice as an innovative approach to detect poor lung health early, monitor respiratory disease progression, and promote lung health. Specifically, we propose that, similar to paediatric height and weight charts used globally to monitor children's growth, lung-function charts could be used for both children and adults to monitor lung health status across the life course. To achieve this proposal, we introduce our free online Lung Function Tracker tool. Finally, we discuss challenges and opportunities for effective implementation of the trajectory concept at population level and outline an agenda for crucial research needed to support such implementation.

Time-dependent gene-environment interactions are essential drivers of asthma initiation and persistence.

Asthma is a clinical syndrome caused by heterogeneous underlying mechanisms with some of them having a strong genetic component. It is known that up to 82% of atopic asthma has a genetic background with the rest being influenced by environmental factors that cause epigenetic modification(s) of gene expression. The interaction between the gene(s) and the environment has long been regarded as the most likely explanation of asthma initiation and persistence. Lately, much attention has been given to the time frame the interaction occurs since the host response (immune or biological) to environmental triggers, differs at different developmental ages. The integration of the time variant into asthma pathogenesis is appearing to be equally important as the gene(s)-environment interaction. It seems that, all three factors should be present to trigger the asthma initiation and persistence cascade. Herein, we introduce the importance of the time variant in asthma pathogenesis and emphasize the long-term clinical significance of the time-dependent gene-environment interactions in childhood.

The genetic framework of primary ciliary dyskinesia assessed by soft computing analysis.

BACKGROUND: International guidelines disagree on how best to diagnose primary ciliary dyskinesia (PCD), not least because many tests rely on pattern recognition. We hypothesized that quantitative distribution of ciliary ultrastructural and motion abnormalities would detect most frequent PCD-causing groups of genes by soft computing analysis. METHODS: Archived data on transmission electron microscopy and high-speed video analysis from 212 PCD patients were re-examined to quantitate distribution of ultrastructural (10 parameters) and functional ciliary features (4 beat pattern and 2 frequency parameters). The correlation between ultrastructural and motion features was evaluated by blinded clustering analysis of the first two principal components, obtained from ultrastructural variables for each patient. Soft computing was applied to ultrastructure to predict ciliary beat frequency (CBF) and motion patterns by a regression model. Another model classified the patients into the five most frequent PCD-causing gene groups, from their ultrastructure, CBF and beat patterns. RESULTS: The patients were subdivided into six clusters with similar values to homologous ultrastructural phenotype, motion patterns, and CBF, except for clusters 1 and 4, attributable to normal ultrastructure. The regression model confirmed the ability to predict functional ciliary features from ultrastructural parameters. The genetic classification model identified most of the different groups of genes, starting from all quantitative parameters. CONCLUSIONS: Applying soft computing methodologies to PCD diagnostic tests optimizes their value by moving from pattern recognition to quantification. The approach may also be useful to evaluate atypical PCD, and novel genetic abnormalities of unclear disease-producing potential in the future.

Extracellular Matrix as a Driver of Chronic Lung Diseases.

The extracellular matrix (ECM) is not just a three-dimensional scaffold that provides stable support for all cells in the lungs, but also an important component of chronic fibrotic airway, vascular, and interstitial diseases. It is a bioactive entity that is dynamically modulated during tissue homeostasis and disease, that controls structural and immune cell functions and drug responses, and that can release fragments that have biological activity and that can be used to monitor disease activity. There is a growing recognition of the importance of considering ECM changes in chronic airway, vascular, and interstitial diseases, including 1) compositional changes, 2) structural and organizational changes, and 3) mechanical changes and how these affect disease pathogenesis. As altered ECM biology is an important component of many lung diseases, disease models must incorporate this factor to fully recapitulate disease-driver pathways and to study potential novel therapeutic interventions. Although novel models are evolving that capture some or all of the elements of the altered ECM microenvironment in lung diseases, opportunities exist to more fully understand cell-ECM interactions that will help devise future therapeutic targets to restore function in chronic lung diseases. In this perspective article, we review evolving knowledge about the ECM's role in homeostasis and disease in the lung.

A core outcome set for bronchiectasis in children and adolescents for use in clinical research: an international consensus study.

Improving the treatment of non-cystic fibrosis bronchiectasis in children and adolescents requires high-quality research with outcomes that meet study objectives and are meaningful for patients and their parents and caregivers. In the absence of systematic reviews or agreement on the health outcomes that should be measured in paediatric bronchiectasis, we established an international, multidisciplinary panel of experts to develop a core outcome set (COS) that incorporates patient and parent perspectives. We undertook a systematic review from which a list of 21 outcomes was constructed; these outcomes were used to inform the development of separate surveys for ranking by parents and patients and by health-care professionals. 562 participants (201 parents and patients from 17 countries, 361 health-care professionals from 58 countries) completed the surveys. Following two consensus meetings, agreement was reached on a ten-item COS with five outcomes that were deemed to be essential: quality of life, symptoms, exacerbation frequency, non-scheduled health-care visits, and hospitalisations. Use of this international consensus-based COS will ensure that studies have consistent, patient-focused outcomes, facilitating research worldwide and, in turn, the development of evidence-based guidelines for improved clinical care and outcomes. Further research is needed to develop validated, accessible measurement instruments for several of the outcomes in this COS.

Influence of age on clinical characteristics, pharmacological management and exacerbations in children with asthma.

BACKGROUND: Asthma trials and guidelines often do not distinguish between adolescents and younger children. Using a large English data set, we evaluated the impact of age on asthma characteristics, management and exacerbations. METHODS: Primary care medical records, 2004-2021, were linked to hospital records. Children were categorised by age at diagnosis and followed until the next age bracket. Ages (based on management guidelines) were 5-8 years, 9-11 years and adolescents (12-16 years). Characteristics evaluated included body mass index, allergies and events before and after diagnosis (symptoms, medication). Exacerbation incidence was calculated. Multivariable Cox proportional hazards determined associations with exacerbations. RESULTS: 119 611 children were eligible: 61 940 (51.8%) 5-8 years, 32 316 (27.7%) 9-11 years and 25 355 (21.2%) adolescents. Several characteristics differed by age; children aged 5-8 years had the highest proportion with eczema, food/drug allergy and cough, but adolescents had the highest proportion with overweight/obesity, aeroallergen sensitisation, dyspnoea and short-acting-beta-agonist only use. Exacerbation rates were highest in the youngest children (per 100 person-years (95% CI): 5-8 years =13.7 (13.4-13.9), 9-11 years =10.0 (9.8-10.4), adolescents =6.7 (6.5-7.0)). Exacerbation risk factors also differed by age; 5-8 years: male, eczema and food/drug allergy were strongly associated, but for children ≥9 years old, obesity and aeroallergen sensitisation were strongly associated. For all children, higher socioeconomic deprivation was significantly associated with having an exacerbation. Delayed diagnosis was most common in children aged 5-8 years and was associated with increased exacerbations across all ages. CONCLUSION: Children's baseline characteristics and exacerbation rates varied according to their age group. Clinical guidelines should consider age at time of diagnosis more discretely than the broad range, 5-16 years, as this appears to impact on asthma severity and management.