A study on 300 asthmatic children, 300 controls and their parents confirms the genetic transmission of allergy and asthma.

BACKGROUND: Several studies have shown the role of genetic factors in allergies, and ascertained that atopic diseases are transmitted by parents, especially by mothers. MATERIALS AND METHODS: In order to explore the genetic risk of a child with a family history (FH) of allergy, we have enrolled into this prospective study 300 children, 173 males and 127 females, aged 3.5 to 7.5 years (median age 4.4 years), that included: family (FH) and personal history skin prick tests (SPTs) and specific IgE (RAST), who attended the Pediatric Allergy and Immunology Division of Rome University because affected with respiratory allergy We have studied the FH of these children asking whether their parents and brothers/sisters had atopic diseases, and detailing whether such diseases were respiratory or food allergies (FA). The parents of all children gave their informed consent. We analyzed data using the X2 method. RESULTS: One hundred and twentyseven parents were atopic (42.3%), in addition to 20 brothers/sisters. In detail 90.2% of fathers, 84% of mothers and 65% of brothers/sisters had asthma or allergic rhinitis (AR). Very less parents had urticaria, especially the mothers and brothers/sisters suffered with atopic dermatitis (AD), and some mothers with FA. In 23 children from these parents most had AD and respiratory allergy. In 300 children comparable for age and sex with no respiratory illness recruited from our out-patient clinic 40 parents, 14 mothers and 26 fathers and 9 brothers/sisters had asthma or AR (p = 0.0001), some fathers had also urticaria and two brothers AD. CONCLUSION: A relevant part of respiratory allergy is not transmitted by mothers. Our prospective study stresses that 42.3% of parents are atopic, and FH of their children was positive for respiratory allergy in 82-92% of cases. Thus respiratory allergy can have an autosomal dominant mode of inheritance, but considering the other atopic diseases, the transmission can be polygenic. The impact of genetic factors in these children is emphasized by the high part of asthmatic brothers/sisters.

Benefits and concerns associated with biotechnology-derived foods: can additional research reduce children health risks?

The development of techniques devised for the genetic manipulation of foods poses new risks for children with food allergy (FA). The introduction of foreign allergenic proteins from different foods into previously tolerated foods may trigger allergic reactions, often complicating with anaphylactic shock in a subset of allergic babies. Children with FA, even if subjected to preventative diets, always challenge the risk of developing allergic manifestations after unintentional intake of a non tolerated food in restaurant settings, with relatives or schoolmates, etc, where product labelling is necessarily lacking. The introduction of potentially allergenic proteins into foods generally considered safe for allergic children can be done deliberately, by either substantially altering the food ingredients, or by genetic manipulation which change the composition or transfer allergens, or unintentionally by qualitycontrol failures, due to contaminations in the production process, or to genetic mismanipulation. There is a controversy between multinationals often favored by governments and consumer association resistance, thus an equidistant analysis poses some unprecedented impediments. The importance of FA and the potential of transgenic plants to bring food allergens into the food supply should not be disregarded. The expression in soybeans of a Brazil nut protein resulted in a food allergen ex-pressed in widely used infant formulas, so paving the way to an often reported multinational debacle. Genetic engineering poses innovative ethical and social concerns, as well as serious challenges to the environment, human health, animal welfare, and the future of agriculture. In this paper will be emphasized practical concepts more crucial for pediatricians.

Benefits and concerns associated with biotechnology-derived foods: can additional research reduce children health risks?

The development of techniques devised for the genetic manipulation of foods poses new risks for children with food allergy (FA). The introduction of foreign allergenic proteins from different foods into previously tolerated foods may trigger allergic reactions, often complicating with anaphylactic shock in a subset of allergic babies. Children with FA, even if subjected to preventative diets, always challenge the risk of developing allergic manifestations after unintentional intake of a non tolerated food in restaurant settings, with relatives or schoolmates, etc, where product labelling is necessarily lacking. The introduction of potentially allergenic proteins into foods generally considered safe for allergic children can be done deliberately, by either substantially altering the food ingredients, or by genetic manipulation which change the composition or transfer allergens, or unintentionally by quality-control failures, due to contaminations in the production process, or to genetic mismanipulation. There is a controversy between multinationals often favored by governments and consumer association resistance, thus an equidistant analysis poses some unprecedented impediments. The importance of FA and the potential of transgenic plants to bring food allergens into the food supply should not be disregarded. The expression in soybeans of a Brazil nut protein resulted in a food allergen expressed in widely used infant formulas, so paving the way to an often reported multinational debacle. Genetic engineering poses innovative ethical and social concerns, as well as serious challenges to the environment, human health, animal welfare, and the future of agriculture. In this paper will be emphasized practical concepts more crucial for pediatricians.

A home-made meat-based formula for feeding atopic babies: a study in 51 children.

BACKGROUND: Several elimination diets have been suggested based on results of skin prick tests (SPTs) or IgE antibodies to foods, thus allowing the identification of the most common offending food(s), including CM (cow's milk), egg, peanut and wheat. But unbalanced, inappropriate dietary manipulation in infants with food allergy (FA) can have critically deleterious consequences. We have investigated the effectiveness of a home-made meat-based formula (HMMBF) (Rezza's diet) in babies with food-induced atopic dermatitis (AD), a common, disabling, chronic disease of infancy. PATIENTS AND METHODS: Rezza's diet was given for two months to 25 infants (median age 6.9 months) affected with AD and FA and the differences of body weight and AD severity score were recorded before and after the diet period. Data were analysed using the T and c2 tests. RESULTS: There was a significant improvement in both the evaluated parameters, whereas in 26 control atopic babies they remained unchanged. CONCLUSION: The results of our study indicate that the HMMBF, also based on the experience of several authors, is a useful oligoantigenic diet for the treatment of food-induced AD, and the prevention of the atopic march.

The prick by prick test is safe and reliable in 58 children with atopic dermatitis and food allergy.

The initial diagnostic approach of food allergy (FA) is to take a detailed history and to perform a careful physical examination in the gastrointestinal, cutaneous and respiratory systems. Subsequently, verification of the relationship between the symptom(s) and the ingestion of the offending food(s) is mandatory, and finally determination of the immunologic mechanisms involved with in vivo and in vitro tests should be performed. The diagnosis of FA in infancy and in childhood is a challenge both for the pediatrician and allergist because it can be easily accomplished only when there is a correlation between the ingestion of the offending food(s) and the onset of the symptoms, and when it can be demonstrated that these symptoms are the consequence of an immunological reaction. However the underlying immunologic mechanisms may be difficult to document, and the only immunologic mechanism easily to prove in current practice is the IgE-mediated one. In this paper on 58 food-allergic children and 60 nonatopic controls we demonstrate that the prick + prick (P+P) tests are very effective and easy to perform. In addition we stress that FA cannot be excluded only because skin prick tests (SPTs) are negative, as recently suggested.

Epidemiology of passive smoke: a prospective study in 589 children.

BACKGROUND: Several studies have found that in children of smoking parents there is an increased incidence of respiratory illnesses and diminished pulmonary function. In infants of smoking atopic parents IgE levels are higher, atopic symptoms start earlier, and children are more likely to wheeze if the mother smokes than if she does not. Maternal smoking of 0.5 packs or more/day was identified as a risk for asthma developing in the 1st year of life. Among the environmental measures of our prevention program there is an absolute prohibition of smoking in the house of a "at risk" baby. MATERIALS AND METHODS: We have studied 289 atopic children, 169 males and 120 females, aged 3.5 to 7.5 years, attending our Division because affected by respiratory allergy. We have asked their parents if they smoked and if there were smoking relatives in their homes, independently of the number or the packs of cigarette smoked. The parents of 300 children comparable for age and sex visiting our outpatient clinic for non respiratory disease served as controls. RESULTS: Smokers were 175 fathers and 109 mothers of the asthmatic children and 153 fathers and 89 mothers of the controls. DISCUSSION: Analysis of data shows that passive smoking is significantly associated with the development of asthma in atopic children, and that males are more at risk than females. We stress that a high number of asthmatic children have atopic, and asthmatic parents. Cigarette smoke is not only a triggering factor of respiratory allergy in babies at risk of atopy, but especially an additional genetic factor, since asthma can be more easily provoked if an atopic parent smokes (more if both parents smoke), and even in children of not atopic, smoking parents.

Significant decrease of IgE antibodies after a three-year controlled study of specific immunotherapy to pollen allergens in children with allergic asthma.

BACKGROUND: Specific immunotherapy (SIT) in children being not an optional treatment should be administered as soon as possible, also in children aged 2-3 years, due to the very early asthma and rhinitis onset, contrarily to opponents continuing to stress the danger of anaphylactic reactions without displaying reliable data. MATERIALS AND METHODS: We report 56 children who underwent SIT and 56 controls seen consecutevely at the Allergy and Immunology Division, Department of Pediatrics, University of Rome "La Sapienza". The control group was treated with all appropriate medications. RESULTS: They were highly in favor of SIT with statistically significant differences. We stress that IgE antibodies significantly decreased after treatment only in the study group, and IgG antibodies very significantly increased after treatment only in the study group. DISCUSSION: We demonstrate that SIT is the only treatment which can alter the natural course of respiratory diseases, whereas drugs represent only a symptomatic treatment.

Allergenicity of a whey hypoallergenic formula in genetically at risk babies: four case reports.

BACKGROUND: Hydrolysate formulas (HF) have been developed with the goal of reducing the allergenicity of cow's milk (CM) proteins, thus providing a suitable formula for feeding babies with CM allergy (CMA). OBJECTIVE: More recently, whey HFs have provoked 208 reactions in babies at high risk of atopy when given for CMA prevention. MATERIAL AND METHODS: We report the clinical and immunologic findings of four babies apparentlly sensitized by a partially whey hydrolysate formula (PWHF) in the nursery. They were exclusively BM (breast milk)-fed by their mothers avoiding highly allergenic foods, but experienced anaphylaxis after a re-feeding with the PWHF. RESULTS: Sensitization to PWHF seems to have occurred in the first days of life. No baby suffered from allergic symptoms during BM-feeding. DISCUSSION: These case reports suggest that a PWHF may be allergenic not only in an already sensitized subject, but also sensitizing in a genetically predisposed baby being immunogenic in the IgE system. These data strongly indicate that maternal diets during BM-feeding, in two instances suggested by family doctors, are effective as a BM complement.

A prospective study of asthma desensitization in 1182 children, 592 asthmatic children and 590 nonatopic controls.

BACKGROUND: The aim of this prospective study was to evaluate the prevalence of allergic asthma and or rhinitis (AR) in 1182 children. Systemic reactions (SRs) to asthma desensitization, previously, specific immunotherapy (SIT) in children with allergic asthma and or AR are scarcely known. MATERIALS AND METHODS: Since 1999, we have consecutively enrolled all children ranging in age from 3 to 11 years attending our Division because affected with severe asthma (592). Controls were 590 nonatopic children matched for age and sex recruited from our outpatient clinic. The study children were treated with a personalized asthma desensitization, the controls were treated with all usual medications. The parents of all children gave their informed consent. Data were analyzed using the X2 method. RESULTS: The 592 atopic children with severe asthma, 370 males and 222 females, aged 3.5 to 10.5 years, tested positive for Der p and Der f (47.1%) or for pollen allergens (52.9%). We have demonstrated a high increase of ashma incidence, since at the start there were 135 asthmatic children and 215 during 2000, with a 62.5% increase. During 2001 there were 242 children, with a 88.8% increase compared to 1999. All of these children were subjected to asthma desensitization, previously SIT (SARM, Roma). At the third yearly control, the study children had a significantly greater reduction as regards days (p = 0.0001) and nights (p = 0.0005) without asthma and drug usage (p = 0.0003) compared with drug-treated children. The number of SPTs and/or sigE to inhalants also decreased, spirometry data were also notably improved The clinically adverse events only were mild or transient. DISCUSSION: The positive results obtained in this large study add to its safety in our opinion because the children were followed by their doctors also on the basis of "as frequently as needed". Accordingly, the early onset of childhood asthma emphasizes that an early treatment is the only means to significantly abate the march of atopic asthma. We have documented an unexpected prevalence of pediatric asthma that should by evaluated in light of the very early asthma development in children which is present even before asthma would be diagnosed based on clinical symptoms The causes of this dramatic increment (10.4%/month in the last six months) may be identified chiefly in the worldwide increase in air pollution and secondhand tobacco smoke.

Neonatal cow milk sensitization in 143 case-reports: role of early exposure to cow's milk formula.

OBJECTIVE: Cow's milk (CM) allergy (CMA) is a disease of infancy, usually appearing in the first months of life. Symptoms triggered by CM at first introduction are not completely defined. The evaluation of infants for possible CMA is one of the more common problems encountered by pediatricians. Purpose of this study was to investigate the prevalence of severe reaction to CM and clinical manifestation triggered by CM administration in the nurseries. MATERIALS AND METHODS: The series includes 143 prospectively studied CM-allergic babies. RESULTS: At the first introduction of CM, at the age of 1-8 months (median 4 months) all infants had immediate symptoms The babies were probably sensitized during the first days of life. Particularly sensitizing appears to be the exposure to CM formulas in the neonatal nursery. DISCUSSION: Little doses of allergens are more sensitizing than larger ones. We provide clear evidence of the immunological effects of oral antigen administration during the neonatal period, and discuss the possible critical allergen transmission to the nursing baby via breast milk (BM).

Nephropathic cystinosis: ineffectiveness of cysteamine therapy for ocular changes.

The biochemical hallmark of nephropathic cystinosis is the intralysosomal accumulation of free cystine in various organs, including the conjunctiva, cornea, bone marrow, leukocytes, lymph nodes, and internal organs. A patient with the infantile form of nephropathic cystinosis develops several renal tubular malfunctions during the first year of life; these eventually lead to end-stage renal failure and eventual death by the time the patient is 10 years of age. Ocular changes are prominent and may be so typical that an early diagnosis can be achieved by an ophthalmologic examination before the nephropathic signs become evident.

Hidden presence of cow's milk proteins in foods.

Cow's milk is one of the first foreign proteins ingested by infants and is one of the most common and potent food allergens. The presence of cow's milk is widespread due also to its unlabelled inclusion as an ingredient, or to errors in cooking, processing and preparation, and in restaurant food. As several foods may contain cow's milk in a hidden form, foods for allergic babies should be prepared at home or with food items with all their ingredients listed on the label. Parents should be provided with appropriate material and instructed how to detect potential sources of hidden cow's milk by judiciously reading food labels to avoid possible untoward reactions. A study on products with potential hidden forms of cow's milk or its proteins is reported herein.

The growing genetic links and the early onset of atopic diseases in children stress the unique role of the atopic march: a meta-analysis.

Allergic asthma and rhinitis, atopic dermatitis, urticaria and food allergy are genetic diseases present in infants and children. Several investigators have provided evidence for a genetic localization for atopy. Babies of atopic parents are at high risk of developing atopic diseases; however, the phenotypic expression of such diseases varies widely in that it can be very mild in some infants and children, severe and frustrating in many, even life-threatening in others, as well as also being common, disabling and chronic. A meta-analysis of all available studies on the age of onset of atopic march was carried out by selecting what appeared to be the most relevant articles in the literature rather than aiming for a comprehensive selection. It was found that in the first year of life, there is the onset of atopic dermatitis in 79.8% (60.2-100%) of babies, of cow's milk allergy in 72.7%, egg allergy in 71%, and fish allergy in 51.3%. Asthma starts in the first year of life in 41.8%, in the second in 49.3%, and within the eighth year in 92.5% of children. Allergic rhinitis begins in 35% of babies in the first year of life, and in 59% or 13-19% in those aged 2-5 years. It seems therefore that up until now the role of pediatric allergy and immunology has been somewhat obscured, as can be witnessed by atopic march. Instead, pediatric allergy and immunology have a substantial, unmatched role, focusing on the early and often very early onset of atopy, which requires strategic intervention in the very first months of life or even before birth. As the main goal of modern medicine is prevention of chronic and severe diseases, the possibility of preventing such disorders in predisposed children has stimulated the imagination of researchers since the beginning of the century, when atopic diseases were not as common as they are now.

Latex allergy in children.

Allergic or immediate hypersensitivity reactions to natural rubber latex have been reported in children with increasing frequency in the last few years, although severe anaphylactic reactions are rare. Indubitably rubber has been employed in thousands and thousands of everyday products for over a century, yet only recently has natural rubber latex allergy been recognized as a substantial medical problem. Children with spina bifida undergoing multiple surgical procedures, as well healthy babies appear at high risk for natural rubber latex allergy, with life-threatening reactions reported during surgery or while playing with balloons. Skin prick testing is the preferred diagnostic method, especially in the prick by prick version. Parents of children with latex allergy should take caution that their babies avoid contact with rubber products, and that a latex-free environment is set during procedures. Since even minimal contact with natural rubber latex products may produce reactions, the primary treatment for latex allergy is avoidance. In this paper we review the new natural rubber latex allergens, as well as the cross-reactions regarding the latex-fruit syndrome since the recent characterization of a number of profilins has also greatly widened the number of possible reactions.

Immunogenicity of hydrolysate formulas in children (part 1). Analysis of 202 reactions.

Cow's milk protein hydrolyzed formulas appeared in the 1940s with the aim of decreasing or eliminating the allergenicity of cow's milk proteins, in addition to reducing the risk of sensitization. In recent years, the so-called "hypoallergenic" formulas have been developed. The use of such hydrolyzed formulas is based on the premise that predigested proteins, when fed as amino acids and peptides, provide nutrients in a nonantigenic form. Thus, protein hydrolyzed formulas have been classified as hypoallergenic. These formulas are processed by heat and enzymatic hydrolysis, and the conformational and sequential structures are more or less changed. The formulas contain peptides of lower molecular weight than the native protein source, which are thought to be less immunogenic. Hydrolyzed formulas appear to be nutritionally adequate and infants generally gain weight until they refuse the formula because of its bad taste. However, caution should be taken when such formulas are given for prolonged periods since no data are available on nutritional assessment of infants exclusively fed hydrolyzed formulas for several months. In this paper we report and discuss more than 202 reactions to different hydrolyzed formulas, including cases of anaphylactic shock and apparent life-threatening events. The cross-reactivity between different hydrolyzed formulas and cow's milk proteins, and the potential immunogenicity of such formulas are discussed. We conclude that none of the hydrolyzed formulas are nonallergenic, both for allergic children and for high-risk babies. Moreover, we suggest that double-blind placebo-controlled food challenge studies in larger cohorts of babies evaluated with well-defined and well-validated diagnostic methods may establish a more reliable prevalence of allergy to hydrolyzed formulas.

Immunogenicity of hydrolysate formulas in children (Part 2): 41 case reports.

Hydrolysate formulas (HF) have been developed with the purpose of reducing the allergenicity of cow's milk proteins, thus providing a suitable formula for feeding babies with cow's milk (CM) allergy (CMA). More recently, used for the treatment of CMA HFs have provoked 211 reactions in babies at high risk of atopy . In this paper we report 81 babies, who attended the Allergy and Clinical Immunology Division of the Pediatric Department of Rome University "La Sapienza" (study children) between June 1997 and October 1998, 41 of whom were tested with Nidina HA (a whey partial HF) and 40 with whole CM. Ninety-seven healthy children with no history of atopy of comparable age and sex formed the control group. All study children reacted to Nidina HA and to CM with similar symptoms. All the control babies tested negative. With these 41 case reports the number of reactions to HFs totals 252. These data strongly indicate that partial HFs may be allergenic not only in an already sensitized individual, but also immunogenic in a predisposed baby.

A three-year prospective study of specific immunotherapy to inhalant allergens: evidence of safety and efficacy in 300 children with allergic asthma.

The effectiveness and safety of specific immunotherapy (SIT) in allergic diseases such as asthma have increasingly come under question. Some authors advocate eliminating SIT as a therapeutic option for allergic patients, since the risks associated with this form of asthma may outweigh its positive effects. However, in a review of twenty-nine controlled studies in 2077 children and an equal number of controls, 27 (93.1%) have shown the effectiveness of SIT in pediatric age for the treatment of asthma due to inhalant allergens (p < 0.0001). The scope of this study was to ascertain whether this form of therapy is safe and effective in pediatrics. 300 children (median age 4.4 years) with asthma due to pollen or house dust mite were prospectively followed for three years. They were randomly divided into two groups: the study group and control group, being almost equal in number of children and clinical characteristics such as sex and age. No child suffered severe reactions due to SIT. Children receiving SIT had significantly greater reductions in days (p = 0.0001) and nights (p = 0.0005) without asthma and drug usage (p = 0.0003), compared with drug-treated children. In addition, the number of asthma attacks (p = 0.0001), and the quality of life were significantly improved in the study group (p = 0.0001). These findings suggest that if suitable allergen extracts are used with close observation of therapeutic indications, and children are followed by their doctors as frequently as required, SIT is effective in the treatment of pediatric asthma, with few adverse effects.

Enzyme-potentiated desensitization in children with asthma and mite allergy: a double-blind study.

The aim of this study was to evaluate the efficacy and safety of enzyme-potentiated desensitization (EPD) in children with asthma. Twenty asthmatic children (14 males and 6 females; median age: 8.5 years) were included in the study. They had positive skin tests to Dermatophagoides pteronyssinus (Dpt), no history of other allergy and had suffered from asthma for at least two years. The children were examined before starting the trial, at the first EPD dose, after 8 weeks, at the second EPD dose and 3 months after the second EPD dose. Blood samples for PRIST and RAST were drawn before the first and at the second EPD dose, and at the last follow-up. Conjunctival provocation tests (CPT) and skin test endpoint determinations were performed with dilutions of a freeze-dried Dpt extract (10-100,000 SQ-U/ml) at the start of the trial and at the last follow-up. Parents kept a diary record of the days with asthma and daily drug usage. The children were randomized to receive either two intradermal placebo injections or the active material with an 8-week interval (November 1991 and January 1992). Ten children received EPD and 10 children placebo. The intradermal injection of EPD (0.05 ml) contained 0.01 ml of beta-glucuronidase (40 Fishman units) and 0.04 ml of a mixture of inhalant allergens (1 Noon unit). The placebo injection consisted of buffer solution only. The EPD-treated children had significantly fewer days with asthma (p = 0.00000). In addition, the EPD-treated children used significantly less medication for the management of asthma attacks (p = 0.00000). At the start of the trial, three out of 10 children in the EPD group and two out of 10 in the placebo group reacted only to the highest dose of allergen used in the CPT (100,000 SQ/ml) (NS). At the last follow-up, the threshold dose in the CPT was 100,000 SQ/ml or more in nine out of 10 children in the EPD group and in four out of 10 children of the placebo group (p = 0.0349). At the last follow-up, one child in the EPD group had a negative CPT with all doses tested. Global clinical evaluation by the investigators showed that eight out of 10 EPD-treated children improved, in comparison with three out of 10 children in the placebo group (p = 0.0349). Assessment by the parents was six out of 10 and four out of 10 improved, respectively (NS). Specific IgE to Dpt, total IgE and skin prick test endpoints before and after EPD showed no significant changes. One child in the placebo group experienced mild urticaria several hours following the second injection. No other local or systemic side effects were reported. The results of the present study provide further data on the effectiveness and safety of EPD in patients with asthma.

Effect of flunisolide on nasal eosinophils and IgE, and symptom score in children with allergic rhinitis.

We evaluated the effect of treatment with flunisolide nasal spray (100 micrograms/day for 3 months) in 24 children with allergic rhinitis on the following parameters: clinical symptoms, absolute number of peripheral and nasal eosinophils, and total IgE levels in nasal secretion. Therapy with flunisolide induced a significant reduction of clinical symptoms (p < 0.001), nasal eosinophils (p < 0.001) and nasal IgE concentration (p < 0.02), while it did not affect the number of peripheral eosinophils. These results indicate that flunisolide can reduce the allergic inflammation of the nasal mucosa.

Isoflavones and soy protein formulas.

A concern has arisen about the possible untoward effects in atopic children of isoflavones present in soy-protein-formulas. However, the studies as yet available fail to support these concerns.