Sputum biomarkers during acute severe asthma attacks in children-a case-control study.

AIM: To study sputum mediator profiles pattern in children with acute severe asthma, compared with stable asthma and healthy controls. The mechanisms of acute severe asthma attacks, such as biomarkers cascades and immunological responses, are poorly understood. METHODS: We conducted a prospective observational case-control study of children aged 5 to 17 years, who presented to hospital with an asthma attack. Children with stable asthma were recruited during outpatient asthma clinic visits. Control children without an asthma diagnosis were recruited from surgical wards. Sputum mediator profiles were measured, and sputum leukocyte differential cell counts were generated. RESULTS: Sputum data were available in 48 children (acute asthma; n = 18, stable asthma; n = 17, healthy controls; n = 13). Acute-phase biomarkers and neutrophil attractants such as IL-6 and its receptor, IL-8 and cytokines linked with bacterial signals, including TNF-R1 and TNF-R2, were elevated in asthma attacks versus stable asthma and healthy controls. T-cell attractant cytokines, associated with viral infections, such as CCL-5, CXCL-10 and CXCL-11, and CXCL-9 (secreted from eosinophils after a viral trigger) were also raised. CONCLUSION: Mediator profiles consistent with bacterial and viral respiratory infections, and T2 inflammation markers co-exist in the sputum of children with acute severe asthma attacks.

An update on controversies in e-cigarettes.

E-cigarettes are electronic nicotine delivery systems (ENDS) which mimic tobacco smoking without the combustion of tobacco. These devices have been misleadingly marketed as "less harmful" alternatives to conventional smoking tobacco products. The e-liquid in e-cigarettes include nicotine, a humectant and other additives including flavourings, colourants, or adulterants such as bacterial and fungal products. In this review, we discuss the contrasting views of the tobacco lobby and most professional societies. We describe the epidemiology of the use of these devices, with a widespread and significant rise in youth e-cigarette use seen in both the USA and Europe. We also describe what is known about the toxicity and mechanisms of EVALI (e-cigarette or vaping associated lung injury). This characterised by respiratory failure with an intense inflammatory response. The presentations are diverse and clinicians should consider vaping as a possible cause of any unusual respiratory illness in patients who have a history of vaping or other use of e-cigarette-related products. Second hand exposure to e-cigarettes is also harmful through respiration and transdermal absorption. E-cigarettes have a worse acute toxicity than tobacco and their long-term toxicity is unknown, and we advocate for the immediate, most vigorous anti-vaping legislation possible.

Processing small sputum samples: a method validation study.

Background: Eosinophilia is frequently a feature of asthma. Sputum analysis can help with the diagnosis and phenotyping of asthma. The current gold standard method is unsuitable for samples <100 mg. However, children frequently produce samples below this threshold.Aim: To compare and validate our modified, small sample (>10 mg and <100 mg) sputum processing method (which omits sample filtering), with the current gold standard. Method: Prospective study of 32 adults with severe asthma providing sputum samples of sufficient size for dual processing. Results: The median (IQR) sample weight was 211.0 (162.4-185.5) mg and 57.5 (22.0-61.6) mg for standard, and small sputum sample processing respectively. There was no statistically significant difference in the median (IQR) cell counts between Method A and B, respectively: eosinophils 3.8% (1.5-14.0) versus 4.9% (1.3-15.5); neutrophils 78.1% (46.5-92.4) versus 65.0% (48.3-86.6). Conclusion: The small sputum sample processing is feasible and reliable, and yields similar results to standard processing.

Respiratory Outcomes at 5-Year Follow-Up in Children with Mannose-Binding Lectin Deficiency: A Retrospective Cohort Study.

OBJECTIVE: Mannose-binding lectin deficiency may predispose children to having increased infection susceptibility. However, there is no conclusive evidence that mannose-binding lectin deficiency is associated with adverse respiratory consequences in children. We aimed to evaluate the effects of mannose-binding lectin deficiency (defined as a level of less than 0.6 mg/L) on clinical, radiological, and microbiological characteristics in children presenting with troublesome respiratory symptoms, as compared to those who are mannosebinding lectin-sufficient. MATERIAL AND METHODS: We conducted a retrospective cohort study to investigate the association between mannose-binding lectin deficiency and respiratory outcomes in children over a period of 10 years in a large teaching hospital. Children presenting with frequent or persistent respiratory symptoms such as a chronic wet cough lasting more than 4 weeks, recurrent lower respiratory tract infections (≥4 infections in a year), or severe respiratory tract infections requiring admission to intensive care or to high dependency unit were included in the study. RESULTS: The study showed no significant difference in clinical outcomes with mannose-binding lectin deficiency and sufficiency. Thirty-two percent of children with mannose-binding lectin deficiency and 30% of those with mannose-binding lectin sufficiency had positive respiratory microbiology. Twenty-three percent of children with mannose-binding lectin deficiency and 24% of those with mannose-binding lectin sufficiency had radiological changes on plain radiographs; also the prevalence of bronchiectasis was similar in both groups. The rates of admission to pediatric intensive care unit were comparable in the 2 groups. CONCLUSIONS: Children with mannose-binding lectin deficiency and sufficiency showed similar clinical, radiological, and microbiological characteristics. Our study suggests that there are no childhood adverse respiratory consequences with mannose-binding lectin deficiency.

It's not all about inhaled treatment: challenges with oral therapy in paediatric respiratory medicine.

Advances in therapies and management of conditions encountered by paediatric respiratory specialists have led to improved outcomes and improved survival rates dramatically in chronic diseases such as cystic fibrosis. However, this has also meant an increase in treatment burden. A variety of inhaled treatments are crucial in managing paediatric respiratory diseases, but these patients also have to take many oral medications. It is widely recognised that developing oral formulations appropriate for the paediatric population can affect how well a product is received by patients and their families. Consideration should be given to palatability and the number of medicines to be administered as these can all contribute to treatment adherence. Polypharmacy specifically in the context of management of patients with cystic fibrosis is not a new concept, but the recently introduced cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies and their potential for interactions and adverse reactions create novel challenges. There are some strategies that families and healthcare professionals can implement to reduce treatment burden. This review will also provide some insight into the life of a teenager with cystic fibrosis and the relative complexities of her treatment and the impacts on daily life. EDUCATIONAL AIMS: To describe the difficulties faced by children with long-term respiratory conditions having to take oral medication.To discuss oral drug interactions that may exist within paediatric respiratory medicine and to consider issues with polypharmacy.To highlight strategies that may be used to reduce the burden of care for children on oral medication.

Precision Medicine for Paediatric Severe Asthma: Current Status and Future Direction.

Asthma is a heterogeneous disease, characterised by different phenotypes and endotypes. Precision medicine in asthma refers to the implementation of a targeted therapy for each individual child, based on the identification of treatable traits, including environmental, immunological and genetic factors. Severe asthma in children is associated with increased hospitalisation rates, a lower quality of life, increased healthcare costs and an increased mortality. In the era of new molecular biologics treatments, it is essential to improve deep phenotyping of children with severe asthma in order to deliver the most effective treatment to each individual child. In this review, we discuss the personalised approach to the assessment and management of severe asthma. We explore the indications and use of the currently licensed biologics, as well as the potential of other emerging treatments.

Why is a paediatric respiratory specialist integral to the paediatric rheumatology clinic?

Systemic connective tissue diseases (CTDs) are characterised by the presence of autoantibodies and multiorgan involvement. Although CTDs are rare in children, they are associated with pulmonary complications, which have a high morbidity and mortality rate. The exact pathophysiology remains unclear. The pleuropulmonary complications in CTD are diverse in their manifestations and are often complex to diagnose and manage. The most common CTDs are discussed. These include juvenile systemic lupus erythematosus, juvenile dermatomyositis, juvenile systemic sclerosis, Sjögren's syndrome and mixed connective tissue disease. We describe the clinical features of the pleuropulmonary complications, focusing on their screening, diagnosis and monitoring. Treatment strategies are also discussed, highlighting the factors and interventions that influence the outcome of lung disease in CTD and pulmonary complications of treatment. Early detection and prompt treatment in a multidisciplinary team setting, including respiratory and rheumatology paediatricians and radiologists, is paramount in achieving the best possible outcomes for these patients.

The role of the pediatrician in caring for children with tracheobronchomalacia.

INTRODUCTION: Children with tracheobronchomalacia (TBM) experience excessive dynamic collapse of the central airway(s). TBM remains an under-diagnosed condition, and there is on ongoing need to raise awareness amongst pediatricians. AREAS COVERED: The literature from PubMed, MEDLINE, EMBASE and Cochrane Controlled Trials Register electronic databases was searched from 1 January 1980 to 14 January 2020. Eligible studies relating to the diagnosis, investigation and management of tracheobronchomalacia in children were included. In this review, we highlight the clinical symptoms of TBM such as the typical barking cough, wheezing, recurrent lower respiratory tract infections or acute life-threatening events. These symptoms worsen when the child is making increased respiratory efforts, such as during crying, coughing and during intercurrent infective illness. This article focuses on the role of the pediatrician in recognizing the condition, the investigative process, and the medical management based on the clinical severity. The principle of management should be holistic, tackling the medical issues of TBM and associated comorbidities, as providing support to families. EXPERT OPINION: There remains a need to devise objective and reproducible bronchoscopic and radiological definitions of severity of TBM. Further studies looking at long-term outcomes of medical therapies used in TBM are required.