Inhaled sodium cromoglycate for asthma in children

Background Sodium cromoglycate has been recommended as maintenance treatment for childhood asthma for many years. Its use has decreased since 1990, when inhaled corticosteroids became popular, but it is still used in many countries. Objectives To determine the efficacy of sodium cromoglycate compared to placebo in the prophylactic treatment of children with asthma. Search strategy We searched the Cochrane Airways Group Trials Register (October 2007), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2007), MEDLINE (January 1966 to November 2007), EMBASE (January 1985 to November 2007) and reference lists of articles. We also contacted the pharmaceutical company manufacturing sodium cromoglycate. In 2007 we updated the review. Selection criteria All double-blind, placebo-controlled randomised trials, which addressed the effectiveness of inhaled sodium cromoglycate as maintenance therapy, studying children aged 0 up to 18 years with asthma. Data collection and analysis Two authors independently assessed trial quality and extracted data. We pooled study results. Main results Of 3500 titles retrieved from the literature, 24 papers reporting on 23 studies could be included in the review. The studies were published between 1970 and 1997 and together included 1026 participants. Most were cross-over studies. Few studies provided sufficient information to judge the concealment of allocation. Four studies provided results for the percentage of symptom-free days. Pooling the results did not reveal a statistically significant difference between sodium cromoglycate and placebo. For the other pooled outcomes, most of the symptom-related outcomes and bronchodilator use showed statistically significant results, but treatment effects were small. Considering the confidence intervals of the outcome measures, a clinically relevant effect of sodium cromoglycate cannot be excluded. The funnel plot showed an under-representation of small studies with negative results, suggesting publication bias. Authors' conclusions There is insufficient evidence to be sure about the efficacy of sodium cromoglycate over placebo. Publication bias is likely to have overestimated the beneficial effects of sodium cromoglycate as maintenance therapy in childhood asthma

A population-based nested case control study on recurrent pneumonias in children with severe generalized cerebral palsy: ethical considerations of the design and representativeness of the study sample

BACKGROUND: In children with severe generalized cerebral palsy, pneumonias are a major health issue. Malnutrition, dysphagia, gastro-oesophageal reflux, impaired respiratory function and constipation are hypothesized risk factors. Still, no data are available on the relative contribution of these possible risk factors in the described population. This paper describes the initiation of a study in 194 children with severe generalized cerebral palsy, on the prevalence and on the impact of these hypothesized risk factors of recurrent pneumonias. METHODS/DESIGN: A nested case-control design with 18 months follow-up was chosen. Dysphagia, respiratory function and constipation will be assessed at baseline, malnutrition and gastro-oesophageal reflux at the end of the follow-up. The study population consists of a representative population sample of children with severe generalized cerebral palsy. Inclusion was done through care-centres in a predefined geographical area and not through hospitals. All measurements will be done on-site which sets high demands on all measurements. If these demands were not met in "gold standard" methods, other methods were chosen. Although the inclusion period was prolonged, the desired sample size of 300 children was not met. With a consent rate of 33%, nearly 10% of all eligible children in The Netherlands are included (n = 194). The study population is subtly different from the non-participants with regard to severity of dysphagia and prevalence rates of pneumonias and gastro-oesophageal reflux. DISCUSSION: Ethical issues complicated the study design. Assessment of malnutrition and gastro-oesophageal reflux at baseline was considered unethical, since these conditions can be easily treated. Therefore, we postponed these diagnostics until the end of the follow-up. In order to include a representative sample, all eligible children in a predefined geographical area had to be contacted. To increase the consent rate, on-site measurements are of first choice, but timely inclusion is jeopardized. The initiation of this first study among children with severe neurological impairment led to specific, unexpected problems. Despite small differences between participants and non-participating children, our sample is as representative as can be expected from any population-based study and will provide important, new information to bring us further towards effective interventions to prevent pneumonias in this population

Measles, mumps and rubella infections and atopic disorders in MMR-unvaccinated and MMR-vaccinated children

Vaccinations have been incriminated in the increase of atopic disorders. Especially the measles-mumps-rubella (MMR) vaccination is often refused by people having a notion that these infectious diseases are beneficial for a healthy development of a child's immune system. This practice endangers herd immunity and is the cause of repeated outbreaks. As the clinical course of infections and also its possible impact on the development of atopy may be different in vaccinated and unvaccinated individuals, we explored in vaccinated and unvaccinated children associations of MMR infection with atopic disorders. Using data from a previously conducted study on the relationship between the diphtheria-tetanus-pertussis-(inactivated) poliomyelitis vaccination in the first year of life and atopic disorders, the study population of 1872 8-12-yr-old was divided as children MMR-unvaccinated and children MMR-vaccinated in the first year of life. Within each group the association between MMR infections and atopic disorders (both as reported by the parents) was assessed. We found a statistically significant positive association between measles infection and 'any atopic disorder' [adjusted odds ratio, OR (95% confidence interval, CI): 1.77 (1.20-2.61)] in the MMR-vaccinated group, mainly because of the relationship with eczema. For rubella there was a negative association with eczema and food allergy in the unvaccinated group: adjusted OR (95% CI): 0.57 (0.38-0.85) and 0.23 (0.07-0.76), respectively. All other associations were not statistically significant. We found a positive relationship between measles infection and any atopy in a group of MMR-vaccinated children and a negative association between rubella infection and eczema and food allergy in unvaccinated children. However, we cannot conclude that these relationships are causal. The negative association with rubella may be an artefact. This study shows no evidence for any protective effects from MMR diseases for the development of atopy and therefore supports conclusions found elsewhere that childhood vaccinations do not cause atopy

Reported pertussis infection and risk of atopy in 8- to 12-yr-old vaccinated and non-vaccinated children

Pertussis infection has been suspected to be a potential causal factor in the development of atopic disease because of the effect of pertussis immunization on specific IgE antibodies. Although several studies found a positive association between pertussis infection and atopic disorders, this relationship has not yet been studied in a population stratified by vaccination status. To assess the association between pertussis infection and atopic disorders in pertussis-unvaccinated children and in pertussis-vaccinated children. Using data from a previously conducted study on the relationship between the diphtheria-tetanus-pertussis-(inactivated) poliomyelitis vaccination in the first year of life and atopic disorders, the study population of 1872 8-12 yr old was divided into children pertussis-unvaccinated and children pertussis-vaccinated in the first year of life. Within each group, the association between pertussis infection and atopic disorders (both as reported by the parents) was assessed. In the unvaccinated group, there were no significant associations between pertussis infection and atopic disorders. In the vaccinated group, all associations between pertussis infection and atopic disorders were positive, the associations with asthma [odds ratio (OR) = 2.24, 95% confidence interval (CI(95%)): 1.36-3.70], hay fever (OR = 2.35, CI(95%): 1.46-3.77) and food allergy (OR = 2.68, CI(95%): 1.48-4.85) being significant. There was a positive association between pertussis infection and atopic disorders in the pertussis vaccinated group only. From the present study, it cannot be concluded whether this association is causal or due to reverse causation

Sublingual immunotherapy with grass pollen is not effective in symptomatic youngsters in primary care

Background: Sublingual immunotherapy (SLIT) is considered safer and more convenient than subcutaneous therapy and therefore has been proposed as especially suitable for children and in primary care. Most efficacy studies in children lack power to be conclusive, and all have been performed in referral centers. Objective: To investigate the efficacy of SLIT with grass pollen allergen in children and adolescents with rhinoconjunctivitis in a primary care setting. Methods: Youngsters aged 6-18 years with hay fever were enrolled from general practices and randomly assigned to receive placebo or grass pollen mix for 2 years. The primary outcome was the mean daily total symptom score (scale 0-15) comprising sneezing, itching nose, watery running nose, nasal blockage, and itching eyes during the months May-August of the second treatment year. Results: Out of 204 youngsters randomized, 168 entered the intention-to-treat analysis (91 verum, 77 placebo). The mean daily total symptom score did not differ between participants allocated to verum and those allocated to placebo (difference for verum minus placebo: -0.08, 95% CI, -0.66-0.50; P =.78). No differences were found for rescue medication-free days, disease-specific quality of life, and overall evaluation of the treatment effect. Local side effects were more frequent in the verum group (39% vs 17% of participants; P =.001). Conclusion: Sublingual immunotherapy with grass pollen in a primary care setting is not effective in children and adolescents. Clinical implications: Currently, SLIT cannot be recommended for general practitioners as a therapeutic modality in youngsters with grass pollen allergy