Optimizing care for children with difficult-to-treat and severe asthma through specialist paediatric asthma centres: expert practical experience and advice.

Severe asthma in children carries an unacceptable treatment burden, yet its rarity means clinical experience in treating it is limited, even among specialists. Practical guidance is needed to support clinical decision-making to optimize treatment for children with this condition.This modified Delphi convened 16 paediatric pulmonologists and allergologists from northern Europe, all experienced in treating children with severe asthma. Informed by interviews with stakeholders involved in the care of children with severe asthma (including paediatricians, nurses and carers), and an analysis of European guidelines, the experts built a consensus focused on the gaps in existing guidance. Explored were considerations for optimizing care for patients needing biologic treatment, and for selecting home or hospital delivery of biologics. This consensus is aimed at clinicians in specialist centres, as well as general paediatricians, paediatric allergologists and paediatric pulmonologists who refer children with the most severe asthma to specialist care. Consensus is based on expert opinion and is intended for use alongside published guidelines.Our discussions revealed three key facets to optimizing care. Firstly, early asthma detection in children presenting with wheezing and/or dyspnoea is vital, with a low threshold for referral from primary to specialist care. Secondly, children who may need biologics should be referred to and managed by specialist paediatric asthma centres; we define principles for the specialist team members, tests, and expertise necessary at such centres, as well as guidance on when homecare biologics delivery is and is not appropriate. Thirdly, shared decision-making is essential at all stages of the patient's journey: clear, concise treatment plans are vital for patient/carer self-management, and structured processes for transition from paediatric to adult services are valuable. The experts identified the potential for specialist paediatric asthma nurses to play a significant role in facilitating multidisciplinary working.Through this project is agreed a framework of practical advice to optimize the care of children with severe asthma. We encourage clinicians and policymakers to implement this practical advice to enhance patient care.

Filaggrin mutations in relation to skin barrier and atopic dermatitis in early infancy.

BACKGROUND: Loss-of-function mutations in the skin barrier gene filaggrin (FLG) increase the risk of atopic dermatitis (AD), but their role in skin barrier function, dry skin and eczema in infancy is unclear. OBJECTIVES: To determine the role of FLG mutations in impaired skin barrier function, dry skin, eczema and AD at 3 months of age and throughout infancy. METHODS: FLG mutations were analysed in 1836 infants in the Scandinavian population-based PreventADALL study. Transepidermal water loss (TEWL), dry skin, eczema and AD were assessed at 3, 6 and 12 months of age. RESULTS: FLG mutations were observed in 166 (9%) infants. At 3 months, carrying FLG mutations was not associated with impaired skin barrier function (TEWL > 11·3 g m-2  h-1 ) or dry skin, but was associated with eczema [odds ratio (OR) 2·89, 95% confidence interval (CI) 1·95-4·28; P < 0·001]. At 6 months, mutation carriers had significantly higher TEWL than nonmutation carriers [mean 9·68 (95% CI 8·69-10·68) vs. 8·24 (95% CI 7·97-8·15), P < 0·01], and at 3 and 6 months mutation carriers had an increased risk of dry skin on the trunk (OR 1·87, 95% CI 1·25-2·80; P = 0·002 and OR 2·44, 95% CI 1·51-3·95; P < 0·001) or extensor limb surfaces (OR 1·52, 95% CI 1·04-2·22; P = 0·028 and OR 1·74, 95% CI 1·17-2·57; P = 0·005). FLG mutations were associated with eczema and AD in infancy. CONCLUSIONS: FLG mutations were not associated with impaired skin barrier function or dry skin in general at 3 months of age, but increased the risk for eczema, and for dry skin on the trunk and extensor limb surfaces at 3 and 6 months.

Diagnosing atopic dermatitis in infancy using established diagnostic criteria: a cohort study.

BACKGROUND: Diagnosing atopic dermatitis (AD) in infants is challenging. OBJECTIVES: To determine the incidence and persistence of eczema and AD in infants using the UK Working Party (UKWP) and Hanifin and Rajka (H&R) criteria. METHODS: A cohort of 1834 infants was examined clinically at 3, 6 and 12 months of age. AD was diagnosed by UKWP (3, 6 and 12 months) and H&R (12 months) criteria. Logistic regression models were used to assess the relationship between AD and eczema. RESULTS: Eczema was observed in 628 (34·2%) infants (n = 240, n = 359 and n = 329 at 3, 6 and 12 months, respectively), with AD diagnosed in 212 (33·7%) infants with any eczema and in 64/78 (82%) infants with eczema at all three visits. The odds of AD were lower with first presentation of eczema at 6 [odds ratio (OR) 0·33, 95% confidence interval (CI) 0·22-0·48] or 12 months (OR 0·49, 95% CI 0·32-0·74) than at 3 months, and higher in infants with eczema at three (OR 23·1, 95% CI 12·3-43·6) or two (OR 6·5, 95% CI 4·3-9·9) visits vs. one visit only. At 12 months, 156/329 (47·4%) fulfilled the UKWP and/or H&R criteria; 27 (8%) fulfilled the UKWP criteria only and 65 (20%) only the H&R criteria. Of the 129 infants who fulfilled the H&R criteria, 44 (34·1%) did not meet the itch criterion. CONCLUSIONS: Used in combination and at multiple timepoints, the UKWP and H&R criteria for AD may be useful in clinical research but may have limited value in most other clinical settings.

Vitamin D levels and atopic eczema in infancy and early childhood in Norway: a cohort study.

BACKGROUND: Epidemiological data and the effect of sun exposure on atopic eczema (AE) suggest that vitamin D (vitD) may be involved in the pathogenesis. OBJECTIVES: To investigate if vitD levels were associated with the presence or severity of AE in the first 2 years of life in children living in south-east Norway. METHODS: Infants, recruited to a clinical trial on acute bronchiolitis (n = 404) and from the general population (n = 240), were examined at 1-13 months (first visit) and at 2 years of age (second visit). Caregivers were interviewed using a structured questionnaire. AE was diagnosed clinically, based on well-established criteria. Disease severity was assessed using the SCORing Atopic Dermatitis index. Blood samples were taken for vitD measurements, using liquid chromatography-tandem mass spectrometry and for common filaggrin mutation analyses. Complete data on AE and vitD were available in 596 and 449 children at the first and second visit, respectively. RESULTS: Atopic eczema was diagnosed in 67 children (11%) at the first visit and in 103 children (23%) at the second. Mean vitD levels were 58·2 nmol L(-1) at the first visit and 66·9 nmol L(-1) at the second. Using vitD level tertiles in multivariate regression analysis, there was no association between vitD levels and AE at either visit, regardless of filaggrin mutation. In children without AE at the first visit, vitD levels did not predict AE at the second. CONCLUSIONS: In this cohort of young children in Norway, we found no association between vitD levels and the presence or severity of AE.