Gabriel R. Bouygue

Incremental prognostic factors associated with cow's milk allergy outcomes in infant and child referrals : the Milan Cow's Milk Allergy Cohort study

BACKGROUND The prognosis for many children with cows milk allergy (CMA) is remission within 3 years, and the clinical parameters that predict duration of disease have not been measured incrementally. OBJECTIVE To prospectively determine prognostic predictors of tolerance in a random cohort of referrals using CMA workup outcomes as covariates and tolerance as the status variable in a duration model of CMA. METHODS The 2001-2006 Milan Cows Milk Allergy Cohort (MiCMAC) enrolled children referrals using double-blind, placebo-controlled food challenges (DBPCFCs) as study end points (confirmation of CMA; onset of tolerance). The Cox regression model was used to analyze all clinical factors that contributed to tolerance. Covariates analyzed were skin, gastrointestinal, and respiratory symptoms; history and demographics at presentation; age at diagnosis and DBPCFC outcomes; sensitization (skin and serum) by cows milk protein fractions; sensitization to other food and inhalant allergens; total IgE levels; specific IgE concentrations for cows milk protein fractions, other ingestants, and aeroallergens; and threshold doses at DBPCFC. Sensitization and DBPCFC were performed at 6-month intervals. RESULTS A total of 112 infants were enrolled (mean [SD] age, 13.85 [9.84] months), and 59 achieved tolerance (mean [SD] age when tolerance was achieved, 27.58 [11.81] months). On univariate analysis, asthma and/or rhinitis at presentation was an independent predictor of persistence (hazard ratio [HR], 2.19; 95% confidence interval [CI], 1.26-3.82). On multivariate analysis, predictors of persistence were a fresh milk wheal diameter increment of 1 mm (HR, 1.18; 95% CI, 1.07-1.31) and a positive skin prick test result with soy (HR, 6.99; 95% CI, 1.56-31.25). CONCLUSIONS This is the first study, to our knowledge, to identify incremental biological predictors of delayed tolerance to cows milk in children that should be integrated into DBPCFC schedules for CMA in infants.

Clinical tolerance of processed foods.

OBJECTIVE To review the effects of technological processing on selected foods of relevance to childhood allergy from the viewpoints of reduced allergenicity, contamination of processed foods by allergens introduced during processing, and ad hoc technologies to produce reduced hypoallergenic products. DATA SOURCES We searched the literature (PubMed/MEDLINE) for articles published between January 1994 and April 2004 using the following keywords: food allergy AND process* OR heat* OR cooking OR toleran*. STUDY SELECTION We drew on our collective clinical and biological experience to restrict retrieved studies to those of more frequent relevance to a hospital allergy practice. RESULTS Comparatively few clinical studies address the modification of allergenicity of food through cooking or processing. Dairy foods are largely unaffected by processing and may be contaminated by, or themselves become, hidden allergens. Hypoallergenic formulas based on milk, soy, or rice and homogenized beef are successful applications of allergenicity reduction via technological processing. Egg, fish, condiments, and vegetables all carry heat-resistant allergens and should also be considered contaminants. Cereals and bakery products are generally well tolerated, but their allergenicity may be enhanced by processing; the case of rice is still open. Peanut allergens are stable, and the evidence is scant that thermal processing affects the allergenicity of soybean and soy hydrolysates. The debate is ongoing about the tolerance of vegetable oils. CONCLUSIONS It is too early to systematize clinical studies based on single procedures. Processing affects antigenicity, but this does not always translate into safety recommendations. Industrial processing is liable to contamination, and monitoring and labeling are industry priorities. Clinicians should evaluate foods by as complete a workup as possible before recommending processed foods.

Avoidance or exposure to foods in prevention and treatment of food allergy

Purpose of reviewTo caution against premature proposals advocating change before epidemiological and clinical evidence warrants such a paradigm shift. Recent findingsUntil 2007, all allergy societies advocated allergen avoidance for prevention and therapy in food allergy. Since then, new evidence has prompted careful re-evaluation of the literature. In primary prevention, delayed introduction of allergenic foods to prevent food allergy was removed from most recommendations. However, there is currently no evidence that allergenic foods ought to be introduced earlier than is recommended for complementary foods, at 4–6 months of age. Here we uphold the view against an emerging school of thought that early and deliberate exposure to allergenic foods may prevent or delay the onset food allergy. While notions of promoting early oral tolerance may have some merit in theory, in practice research remains inconclusive. Of recent development are treatment advances as regards established food allergy, using food allergens to induce tolerance in highly selected populations of allergic children. However, the investigators themselves strongly warn of significant risks and stress the need to optimize safety and understand longer-term implications before these trials can be applied to routine clinical practice. In this paper we endorse the current recommendation that children with confirmed food allergy should avoid foods implicated in immediate reactions. SummaryIt is currently inappropriate and potentially dangerous to advocate deliberate exposure to foods involved in serious reactions against current recommendations and particularly so among food allergic children until more basic and clinical research become available.

Molecular diagnosis of cow's milk allergy.

Purpose of reviewTo identify and discuss studies on the molecular diagnosis of cows milk allergy (CMA) with a view to update allergists since a general review of the methodology in 2006. Recent findingsSeven basic research studies reporting the use of component-resolved diagnostics in CMA were found. All studies were on children positively reacting to a formal challenge with cows milk. Six studies used natural allergens and three used recombinant milk proteins. Microarray platforms were customized and, thus, differed across studies. Three studies assessed the association between molecular-scale patterns and different presentations of the condition, that is the association between anaphylaxis, gastrointestinal symptoms and other severe phenotypes and the pattern of protein sensitization. Two studies assessed the association between positive oral food challenge and the persistence of milk allergy over time. Protein profiling could be useful to indicate appropriate specific immunotherapy. SummaryAccurate diagnosis of CMA is challenging and essential. The determination of the immunoglobulin E (IgE)-mediated response to sequenced and characterized allergens may be more useful in predicting the presence and severity of clinical allergy than the currently used skin or blood tests performed with whole extracts. However, as component recognition pattern heterogeneity is observed in different areas, further clinical studies are essential to correlate useful molecular diagnostics and biological markers with disease and patient profiles. Until such markers are found and validated in different age groups, oral food challenge remains the reference standard for the diagnosis of CMA.

Impact of dietary regimen on the duration of cow's milk allergy: a random allocation study

Background The impact of diet on cows milk allergy (CMA) duration and whether exposure to residual amounts of cows milk protein influences the onset of tolerance are unknown.

A Case of Fulminant "Talc Pneumoconiosis": Where is the Smoking Gun?

We refer to the case presented by Yoram Dekel and colleagues in the Vol. 10, No. 4 issue of the Journal, which sets out prima facie evidence of talc inhalation from “excessive cosmetic use of talc” as prime suspect in a 42year old woman’s demise. We would plead that the proximal cause of death is far from established. The rapid progression of pancardiac failure in a patient with a recent onset of pulmonary hypertension and cor pulmonale is unconvincing. Documented pulmonary hypertension is attributed to interstitial fibrosis, but this is not backed up by X-ray findings. Neither left heart function before the final crisis nor systemic blood pressure are reported and, despite a normal left ventricular scan, left heart hypertrophy was found at autopsy. Cardiac enzymology is omitted. This leaves the interpretation of acute cardiomyopathy either of dilatory or viral etiology undecided. The crystals found at microscopy are actually compatible with other sheet silicates apart from talc. “Talc particles were exceedingly large and not of the usual granular configuration” but cosmetic-grade talc is highly purified. It is significant that aluminium was found as this element distinguishes talc from the aluminium silicate pyrophillite [Al2 (Si4O10) (OH2)], which is similar to most talcs [Mg3(Si2O5)2 (OH)2], is used in the construction and automobile industries and causes pyrophillitosis. Both minerals have the same hardness and specific mass volume (2.6-2.9 g/cm). The “elemental analysis” (Figure 5) does not clearly indicate if peaks refer to quantities or energy states, and which method of spectrometry was used to identify talc from related phyllosilicate particulates. Cement inhalation, e.g., would be hard to rule out outside occupational settings without the use of spectrometry. As other environmental exposures cannot be totally excluded from the scant description of the case (an estimate of the quantity of particulate matter found is not reported), most of the evidence against cosmetic talc, without “scene of crime” sampling, remains circumstantial.