Samantha Moss

The oral corticosteroid-sparing effect of omalizumab in children with severe asthma

Objective To report the oral corticosteroid-sparing effect of omalizumab in children with severe asthma. Design 16-week therapeutic trial. Setting Tertiary paediatric asthma clinic. Patients 34 children with severe asthma maintained on oral prednisolone (median age 12 years; 15 children <12 years and 19 children ≥12 years). Interventions Fortnightly or monthly subcutaneous injections of omalizumab; the dose was calculated as per manufacturers instructions based on body weight and serum immunoglobulin E concentration. Main outcome measures Reduction in prednisolone dose; mini-Asthma Quality of Life Questionnaire (AQLQ); Childhood Asthma Control Test (ACT); forced expiratory volume in 1 s (FEV1). Results Median daily prednisolone dose reduced from 20 mg to 5 mg (n=34, p<0.0001), including seven children who stopped prednisolone completely. Mini-AQLQ score increased from 3.5 to 5.9 (n=24, p<0.0001). Childhood ACT score increased from 12 to 20 (n=23, p=0.0001). FEV1 increased from 2.10 to 2.25 litres (n=31, non-significant). The reduction in prednisolone dose and improvements in mini-AQLQ and childhood ACT were significant in children both under and over 12 years of age, with no differences in outcome detected between these two groups. Conclusions A 16-week therapeutic trial of omalizumab allowed a significant reduction in daily prednisolone dose and was associated with improvements in asthma control and quality of life in 34 children with severe asthma. Similar benefits were seen in children both above and below 12 years of age. These uncontrolled data are very encouraging. There is an urgent requirement for a multicentre randomised placebo-controlled trial of omalizumab in children with severe asthma, with reduction in oral corticosteroid dose as the primary outcome measure.

Towards safer neonatal transfer: the importance of critical incident review

Background: Critical incidents are common during the inter-hospital transfer of sick patients, and infants are an especially vulnerable group. Aims: To examine the effect of critical incident review on the number of adverse events during inter-hospital transfer of sick infants. Methods: Critical incidents over an eight year period are reported from a single neonatal transfer service before and after major service changes were made. The changes were instigated as part of ongoing critical incident reviews. Results: Changes made as a result of critical incident review significantly reduced the number of incidents contributed to by poor preparation, transport equipment or clinical problems, ambulance delays, and ambulance equipment failure. Conclusions: The continuous process of critical incident reporting and review can reduce the number of adverse events during the transfer of critically ill infants.

Immunogenicity of a Heptavalent Conjugate Pneumococcal Vaccine Administered Concurrently with a Combination Diphtheria, Tetanus, Five-Component Acellular Pertussis, Inactivated Polio, and Haemophilus influenzae Type b Vaccine and a Meningococcal Group C Conjugate Vaccine at 2, 3, and 4 Months of Age

ABSTRACT The immunogenicities of conjugate pneumococcal vaccines have been demonstrated when they are administered at 2, 3, and 4 months of age. There is a paucity of data on the immunogenicity of this vaccine when it is administered concurrently with other vaccines in the primary immunization schedule of the United Kingdom. We immunized 55 term infants at 2, 3, and 4 months of age with the seven-valent pneumococcal conjugate vaccine (PCV7), the meningococcal group C conjugate (MCC) vaccine, and the diphtheria, tetanus, five-component acellular pertussis, inactivated polio, and Haemophilus influenzae type b (DTaP5/IPV/Hib-TT) vaccine. The immune responses to the H. influenzae type b (Hib), MCC, and tetanus vaccines were measured at 2, 5, and 12 months of age; and the immune responses to PCV7 were measured at 2 and 5 months and then either at 12 months or following a 4th dose of PCV7. There were increases in the geometric mean concentrations (GMCs) of all antigens postimmunization. Greater than or equal to 90% of the infants achieved putatively protective levels postimmunization for all vaccine antigens except pneumococcal serotype 6B and Hib. The GMCs of the PCV7 serotypes increased following a 4th dose, although one infant had not reached putative levels of protection against serotype 6B. In conclusion, when infants were vaccinated according to the schedule described above, they had lower postprimary immunization responses to Hib, meningococcus group C capsular polysaccharide, and pneumococcal serotype 6B than the responses demonstrated by use of the other schedules. Despite this finding, there was a good response following a 4th dose of PCV7.

Responses to a conjugate pneumococcal vaccine in preterm infants immunized at 2, 3, and 4 months of age.

ABSTRACT Preterm infants are at an increased risk of invasive pneumococcal disease infection and, additionally, have a diminished response to Haemophilus influenzae type b (Hib) conjugate vaccines. There are little data examining the response of preterm infants to a seven-valent pneumococcal conjugate vaccine (PCV7). We examined the responses of preterm infants immunized at 2, 3, and 4 months of age to PCV7. A total of 133 preterm and 54 term infants were immunized with PCV7 and the Neisseria meningitidis group C (MCC), diphtheria, tetanus, pertussis, polio, and Hib vaccines. Pneumococcal serotype-specific IgG was measured by enzyme-linked immunosorbent assay (ELISA) pre- and postimmunization and at 12 months or following a booster of PCV7. Term and preterm responses were compared using linear and logistic regression analyses. Term infants had higher preimmunization geometric mean concentrations (GMCs) for all serotypes. Preterm infants had lower postimmunization GMCs for serotype 23F. Gestational age affected postimmunization GMCs for serotypes 4, 6B, and 23F. Preterm infants were as likely to have levels of ≥0.35 μg/ml as term infants for all serotypes except 23F. The proportions of infants with titers of ≥0.35 μg/ml for all 7 serotypes were comparable between groups. A total of 28 of 29 term infants who received a booster had levels of ≥0.35 μg/ml for all serotypes. One infant had undetectable levels for serotype 6B. Of the 32 preterm infants boosted, 9 had levels of <0.35 μg/ml for 1 serotype, and 1 had levels of <0.35 μg/ml for 2 serotypes. In nonboosted infants, GMCs for all serotypes except 6B had fallen by 12 months of age. These results support the need for a booster dose in the second year of life.

RSV: Immunoprophylaxis and non‐invasive respiratory support in ex‐preterms: A northern UK perspective

Recent guidance has suggested that immunoprophylaxis with monoclonal antibody against respiratory syncytial virus (RSV) should be extended to ex‐preterm infants who are moderate‐to‐late‐preterm and discharged home during the RSV season. Noninvasive respiratory support (NIV) for infants with bronchiolitis is becoming widespread with little supporting evidence for efficacy over nonpressure support methods. We used multicentre prospective audit and service evaluation to evaluate whether extension of current practice in line with the guidance would provide a clinical or cost benefit, and whether NIV provides any benefits in the ex‐preterm population. The prevalence of bronchiolitic illness requiring admission in our population was similar to other studies (2.5%). We found that the majority of ex‐preterm infants with RSV positive bronchiolitis who required NIV did not meet the extended criteria for immunisation. Our data suggest that extending RSV prophylaxis as recommended would be unlikely to reduce numbers of infants requiring respiratory support for RSV. NIV use has been widely adopted (9% of ‘bronchiolitic’ admissions) in our region but the data do not support it as a useful adjunct for ex‐preterms with RSV positive illness requiring respiratory support: it does not appear to reduce the need for subsequent formal ventilation. Our study does not support a case for change to more widespread, protocol driven immunisation for RSV. Further research is needed in a randomised, controlled setting to examine the use of NIV in bronchiolitis in a wider context. Pediatr Pulmonol. 2015; 50:1119–1127.

Controversies in Neonatal Sepsis: Immunomodulation in the Treatment and Prevention of Neonatal Sepsis

Whilst the concept of replacing the neonatal immunological deficit to prevent or treat systemic sepsis is theoretically attractive, the results from clinical trials performed to date are perhaps less dramatic than expected. The reasons for this are likely to be multifactorial, but include the recruitment of low risk infants who are not septic or neutropenic, and use of inappropriate immunoglobulin preparations that contains little or no antibody effective against pathogens causing neonatal sepsis. There may well be cheaper, more effective, but less glamorous, methods of preventing infection in the preterm infant. There is accumulating evidence regarding the role of prophylactic broad spectrum antibiotics on neonatal gut flora and the influence of early enteral feeding with a correct milk formula can have on encouraging “friendly” gut bacteria. The role of growth factors and immunoglobulin preparations in the treatment and prophylaxis of neonatal sepsis has not yet been established and these products should only be used in the context of large randomised controlled clinical trials until there is clear evidence of benefit (or absence of benefit) in their use.