Adrian J. Lowe

Prevalence of challenge-proven IgE-mediated food allergy using population-based sampling and predetermined challenge criteria in infants

BACKGROUND Several indicators suggest that food allergy in infants is common and possibly increasing. Few studies have used oral food challenge to measure this phenomenon at the population level. OBJECTIVE To measure the prevalence of common IgE-mediated childhood food allergies in a population-based sample of 12-month-old infants by using predetermined food challenge criteria to measure outcomes. METHODS A sampling frame was used to select recruitment areas to attain a representative population base. Recruitment occurred at childhood immunization sessions in Melbourne, Australia. Infants underwent skin prick testing, and those with any sensitization (wheal size ≥ 1 mm) to 1 or more foods (raw egg, peanut, sesame, shellfish, or cows milk) were invited to attend an allergy research clinic. Those who registered a wheal size ≥ 1 mm to raw egg, peanut, or sesame underwent oral food challenge. RESULTS Amongst 2848 infants (73% participation rate), the prevalence of any sensitization to peanut was 8.9% (95% CI, 7.9-10.0); raw egg white, 16.5% (95% CI, 15.1-17.9); sesame, 2.5% (95% CI, 2.0-3.1); cows milk, 5.6% (95% CI, 3.2-8.0); and shellfish, 0.9% (95% CI, 0.6-1.5). The prevalence of challenge-proven peanut allergy was 3.0% (95% CI, 2.4-3.8); raw egg allergy, 8.9% (95% CI, 7.8-10.0); and sesame allergy, 0.8% (95% CI, 0.5-1.1). Oral food challenges to cows milk and shellfish were not performed. Of those with raw egg allergy, 80.3% could tolerate baked egg. CONCLUSION More than 10% of 1-year-old infants had challenge-proven IgE-mediated food allergy to one of the common allergenic foods of infancy. The high prevalence of allergic disease in Australia requires further investigation and may be related to modifiable environmental factors.

Atopic dermatitis and the atopic march revisited

Atopic dermatitis (AD) has become a significant public health problem because of increasing prevalence, together with increasing evidence that it may progress to other allergic phenotypes. While it is now acknowledged that AD commonly precedes other allergic diseases, a link termed ‘the atopic march’, debate continues as to whether this represents a causal relationship. An alternative hypothesis is that this association may be related to confounding by familial factors or phenotypes that comanifest, such as early‐life wheeze and sensitization. However, there is increasing evidence from longitudinal studies suggesting that the association between AD and other allergies is independent of confounding by comanifest allergic phenotypes. The hypotheses on plausible biological mechanisms for the atopic march focus on defective skin barrier function and overexpression of inflammatory mediators released by the skin affected by AD (including thymic stromal lymphopoietin). Both human and animal studies have provided evidence supporting these potential biological mechanisms. Evidence from prevention trials is now critical to establishing a causal nature of the atopic march. An emerging area of research is investigation into environmental modifiers of the atopic march. Such information will assist in identifying secondary prevention strategies to arrest the atopic march. Despite much research into the aetiology of allergies, little progress has been made in identifying effective strategies to reduce the burden of allergic conditions. In this context, the atopic march remains a promising area of investigation.

Fine-needle aspiration may miss a third of all malignancy in palpable thyroid nodules: a comprehensive literature review.

Background:Fine-needle aspiration (FNA) is currently the primary diagnostic procedure in diagnosing thyroid malignancy and guides surgeons on patient selection for thyroidectomy for thyroid nodules. Diagnostic sensitivity is reported to be approximately 80%; however, patients with negative FNA results do not necessarily undergo surgery and are often not considered in statistical analysis. This may lead to bias in previous reported sensitivity of FNA. The aim of this study was to assess the diagnostic performance attributes of FNA based on a comprehensive review and summary of previous literature. Methods:A comprehensive review of published literature from 1966 to 2005 was performed, using structured selection and appraisal methods to include all studies that have assessed the sensitivity of FNA for detecting thyroid malignancy in palpable thyroid nodules. A statistical modeling study was designed to estimate the possible true sensitivity and specificity of FNA. Results:Twelve studies fulfilled inclusion criteria and were included in the review. Only 1 study had greater than 25% of patients with negative FNA results who proceeded to thyroidectomy. Statistical modeling indicated that the sensitivity of FNA is highly dependent on the risk of malignancy in the patients with negative FNA results who did not undergo thyroidectomy; in the “same risk” scenario, where the risk of malignancy in the whole group with negative FNA result was assumed to be the same as that in patients with negative FNA results who underwent surgical biopsy; sensitivity could be as low as 66% (confidence interval [CI]: 65–68%). Conclusion:Based on existing reports, the true diagnostic attributes of FNA for thyroid malignancy in palpable nodules are uncertain and FNA could miss up to a third of all thyroid malignancy. Further research is required to investigate the incidence of malignancy in FNA negative cases and to determine the additive effect of clinical judgment.

Vitamin D insufficiency is associated with challenge-proven food allergy in infants

BACKGROUND Epidemiological evidence has shown that pediatric food allergy is more prevalent in regions further from the equator, suggesting that vitamin D insufficiency may play a role in this disease. OBJECTIVE To investigate the role of vitamin D status in infantile food allergy. METHODS A population sample of 5276 one-year-old infants underwent skin prick testing to peanut, egg, sesame, and cows milk or shrimp. All those with a detectable wheal and a random sample of participants with negative skin prick test results attended a hospital-based food challenge clinic. Blood samples were available for 577 infants (344 with challenge-proven food allergy, 74 sensitized but tolerant to food challenge, 159 negative on skin prick test and food challenge). Serum 25-hydroxyvitamin D levels were measured by using liquid chromatography tandem mass spectrometry. Associations between serum 25-hydroxyvitamin D and food allergy were examined by using multiple logistic regression, adjusting for potential risk and confounding factors. RESULTS Infants of Australian-born parents, but not of parents born overseas, with vitamin D insufficiency (≤50 nmol/L) were more likely to be peanut (adjusted odds ratio [aOR], 11.51; 95% CI, 2.01-65.79; P=.006) and/or egg (aOR, 3.79; 95% CI, 1.19-12.08; P=.025) allergic than were those with adequate vitamin D levels independent of eczema status. Among those with Australian-born parents, infants with vitamin D insufficiency were more likely to have multiple food allergies (≥2) rather than a single food allergy (aOR, 10.48; 95% CI, 1.60-68.61 vs aOR, 1.82; 95% CI, 0.38-8.77, respectively). CONCLUSIONS These results provide the first direct evidence that vitamin D sufficiency may be an important protective factor for food allergy in the first year of life.

The influence of childhood traffic-related air pollution exposure on asthma, allergy and sensitization: a systematic review and a meta-analysis of birth cohort studies

The impact of early childhood traffic‐related air pollution (TRAP) exposure on development of asthma and allergies remains unclear. Birth cohort studies are the best available study design to answer this question, but the evidence from such studies has not been synthesized to date. We conducted a systematic review and meta‐analyses of published birth cohort studies to understand the association between early childhood TRAP exposure, and subsequent asthma, allergies and sensitization. Increased longitudinal childhood exposure to PM2.5 and black carbon was associated with increasing risk of subsequent asthma in childhood (PM2.5: OR 1.14, 95%CI 1.00 to 1.30 per 2 μg/m3 and black carbon: OR 1.20, 95%CI 1.05 to 1.38 per 1 × 10−5 m−1). Also, early childhood exposure to TRAP was associated with development of asthma across childhood up to 12 years of age. The magnitude of these associations increased with age, and the pattern was prominent for PM2.5. Increasing exposure to PM2.5 was associated with sensitization to both aero‐ and food allergens. There was some evidence that TRAP was associated with eczema and hay fever. In summary, exposure to TRAP was related to asthma and allergic diseases. However, the substantial variability across studies warrants long‐term birth cohort studies with regular repeated follow‐ups to confirm these findings.

Breastfeeding and asthma and allergies: a systematic review and meta‐analysis

To systematically review the association between breastfeeding and childhood allergic disease.

Paracetamol use in early life and asthma: prospective birth cohort study

Objective To determine if use of paracetamol in early life is an independent risk factor for childhood asthma. Design Prospective birth cohort study. Setting Melbourne Atopy Cohort Study. Participants 620 children with a family history of allergic disease, with paracetamol use prospectively documented on 18 occasions from birth to 2 years of age, followed until age 7 years. Main outcome measures The primary outcome was childhood asthma, ascertained by questionnaire at 6 and 7 years. Secondary outcomes were infantile wheeze, allergic rhinitis, eczema, and skin prick test positivity. Results Paracetamol had been used in 51% (295/575) of children by 12 weeks of age and in 97% (556/575) by 2 years. Between 6 and 7 years, 80% (495/620) were followed up; 30% (148) had current asthma. Increasing frequency of paracetamol use was weakly associated with increased risk of childhood asthma (crude odds ratio 1.18, 95% confidence interval 1.00 to 1.39, per doubling of days of use). However, after adjustment for frequency of respiratory infections, this association essentially disappeared (odds ratio 1.08, 0.91 to 1.29). Paracetamol use for non-respiratory causes was not associated with asthma (crude odds ratio 0.95, 0.81 to 1.12). Conclusions In children with a family history of allergic diseases, no association was found between early paracetamol use and risk of subsequent allergic disease after adjustment for respiratory infections or when paracetamol use was restricted to non-respiratory tract infections. These findings suggest that early paracetamol use does not increase the risk of asthma.

Effect of a partially hydrolyzed whey infant formula at weaning on risk of allergic disease in high-risk children: A randomized controlled trial

BACKGROUND Partially hydrolyzed whey formula (pHWF) has been recommended for infants with a family history of allergic disease at the cessation of exclusive breast-feeding to promote oral tolerance and prevent allergic diseases. OBJECTIVE To determine whether feeding infants pHWF reduces their risk of allergic disease. METHODS A single-blind (participant) randomized controlled trial was conducted to compare allergic outcomes between infants fed a conventional cows milk formula, a pHWF, or a soy formula. Before birth, 620 infants with a family history of allergic disease were recruited and randomized to receive the allocated formula at cessation of breast-feeding. Skin prick tests to 6 common allergens (milk, egg, peanut, dust mite, rye grass, and cat dander) were performed at 6, 12, and 24 months. The primary outcome was development of allergic manifestations (eczema and food reactions) measured 18 times in the first 2 years of life. RESULTS Follow-up was complete for 93% (575/620) at 2 years and 80% (495/620) at 6 or 7 years of age. There was no evidence that infants allocated to the pHWF (odds ratio, 1.21; 95% CI, 0.81-1.80) or the soy formula (odds ratio, 1.26; 95% CI, 0.84-1.88) were at a lower risk of allergic manifestations in infancy compared with conventional formula. There was also no evidence of reduced risk of skin prick test reactivity or childhood allergic disease. CONCLUSION Despite current dietary guidelines, we found no evidence to support recommending the use of pHWF at weaning for the prevention of allergic disease in high-risk infants.

Epilepsy Surgery for Pathologically Proven Hippocampal Sclerosis Provides Long‐term Seizure Control and Improved Quality of Life

Summary:  Purpose: To examine long‐term seizure and quality‐of‐life outcome in a homogeneous group of patients after temporal lobectomy with pathologically proven hippocampal sclerosis (HS). Previous research has had limited follow‐up (generally <2 years) and has grouped patients across multiple pathologies.

Delayed introduction of solid feeding reduces child overweight and obesity at 10 years.

Background:The function that the timing of introduction of solid foods may have in the development of child obesity has not been adequately explored, either as a potential confounder of the relationship between breastfeeding and child obesity, or as an independent modifiable risk factor.Objective:To determine the association between infant feeding practices and child overweight/obesity.Patients and Methods:Six hundred and twenty subjects were recruited antenatally from 1990 to 1994. A total of 18 telephone interviews over the first 2 years of life recorded infant feeding practices. At mean age of 10 years, height and weight were measured for 307 subjects. Multiple logistic regression was used to determine whether infant feeding practices (duration of exclusive and any breastfeeding, and age at introduction of solid foods) were associated with odds of being overweight/obese (internationally age- and sex-standardized body mass index category) at age 10 years, after adjustment for confounders.Results:Delayed introduction of solid foods was associated with reduced odds of being overweight/obese at age 10 years, after controlling for socioeconomic status, parental smoking and childcare attendance (adjusted odds ratio (aOR)=0.903 per week, 95% CI=0.841–0.970, P=0.005). Antenatal parental smoking was associated with overweight/obesity at age 10 years (aOR=3.178, 95% CI=1.643–6.147, P=0.001). Duration of exclusive or any breastfeeding was not associated with the outcome.Conclusions:Delayed introduction of solids is associated with reduced odds of child overweight/obesity. Wider promotion of current infant feeding guidelines could have a significant impact on the rates of child overweight and obesity.