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.

Effect of previous vaccination with pneumococcal conjugate vaccine on pneumococcal polysaccharide vaccine antibody responses.

During the past 10 years, pneumococcal conjugate vaccine (PCV) has become part of the standard childhood vaccination programme. This may impact upon the diagnosis of polysaccharide antibody deficiency by measurement of anti-polysaccharide immunoglobulin (Ig)G after immunization with unconjugated pneumococcal polysaccharide vaccine (PPV). Indeed, contrary to PPV, PCV induces a T-dependent, more pronounced memory response. The antibody response to PPV was studied retrospectively in patients referred for suspected humoral immunodeficiency. The study population was divided into four subgroups based on age (2-5 years versus ≥ 10 years) and time tested (1998-2005 versus 2010-12). Only 2-5-year-old children tested in 2010-12 had been vaccinated with PCV prior to PPV. The PCV primed group showed higher antibody responses for PCV-PPV shared serotypes 4 and 18C than the unprimed groups. To a lesser extent, this was also found for non-PCV serotype 9N, but not for non-PCV serotypes 19A and 8. Furthermore, PCV-priming elicited a higher IgG2 response. In conclusion, previous PCV vaccination affects antibody response to PPV for shared serotypes, but can also influence antibody response to some non-PCV serotypes (9N). With increasing number of serotypes included in PCV, the diagnostic assessment for polysaccharide antibody deficiency requires careful selection of serotypes that are not influenced by prior PCV (e.g. serotype 8). Further research is needed to identify more serotypes that are not influenced.

Value of allohaemagglutinins in the diagnosis of a polysaccharide antibody deficiency.

Polysaccharide antibody deficiency is characterized by a poor or absent antibody response after vaccination with an unconjugated pneumococcal polysaccharide vaccine. Allohaemagglutinins (AHA) are antibodies to A or B polysaccharide antigens on the red blood cells, and are often used as an additional or alternative measure to assess the polysaccharide antibody response. However, few studies have been conducted to establish the clinical significance of AHA. To investigate the value of AHA to diagnose a polysaccharide antibody deficiency, pneumococcal polysaccharide antibody titres and AHA were studied retrospectively in 180 subjects in whom both tests had been performed. Receiver operating characteristic curves for AHA versus the pneumococcal vaccine response as a marker for the anti-polysaccharide immune response revealed an area under the curve between 0·5 and 0·573. Sensitivity and specificity of AHA to detect a polysaccharide antibody deficiency, as diagnosed by vaccination response, were low (calculated for cut-off 1/4-1/32). In subjects with only low pneumococcal antibody response, the prevalence of bronchiectasis was significantly higher than in subjects with only low AHA (45·5 and 1·3%, respectively) or normal pneumococcal antibody response and AHA (2·4%). A logistic regression model showed that low pneumococcal antibody response but not AHA was associated with bronchiectasis (odds ratio 46·2). The results of this study do not support the routine use of AHA to assess the polysaccharide antibody response in patients with suspected immunodeficiency, but more studies are warranted to clarify the subject further.