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Biomedical subjects

Gideon Lack

Publications and source records attributed to Gideon Lack.

At least 19 recordsLinked to original sources

Grass pollen immunotherapy as an effective therapy for childhood seasonal allergic asthma.

BACKGROUND: Few studies have investigated the use of specific immunotherapy (SIT) for childhood seasonal allergic asthma. OBJECTIVE: We sought to examine the efficacy and safety of SIT with Alutard SQ grass pollen (Phleum pratense Alutard SQ; ALK-Abelló, Hørsholm, Denmark) in children with seasonal allergic asthma. METHODS: A randomized, double-blind, placebo-controlled study assessing the efficacy of grass pollen SIT over 2 pollen seasons was performed. Children (3-16 years) with a history of seasonal allergic asthma sensitized to grass pollen (P pratense) and requiring at least 200 microg of inhaled beclomethasone equivalent per day were enrolled. Subjects with symptomatic asthma or rhinoconjunctivitis outside the grass pollen season were excluded. The primary outcome measure was a combined asthma symptom-medication score during the second pollen season. Secondary outcome measures included end-point titration skin prick testing and conjunctival and bronchial provocation testing to allergen, sputum eosinophilia, exhaled nitric oxide, and adverse events. RESULTS: Thirty-nine subjects were enrolled. Thirty-five subjects provided data for analysis. The use of SIT was associated with a substantial reduction in asthma symptom-medication score compared with that after placebo (P = .04). There were also significant reductions in cutaneous (P = .002), conjunctival (P = .02), and bronchial (P = .01) reactivity to allergen after SIT compared with that after placebo. The 2 groups had similar levels of airway inflammation, despite a trend toward less inhaled steroid use in the active group. No serious adverse events were reported, and no subjects withdrew because of adverse events. CONCLUSION: The study has shown that SIT is effective and well tolerated in children with seasonal allergic asthma to grass pollen.

Adolescent↗

The predictive value of early life total immunoglobulin E measurement in identifying atopic children in a population-based birth cohort study.

Atopy is common and the prevalence amongst children is rising. Measurements in early childhood that can predict subsequent development of atopy could be clinically useful for targeting preventive measures. We used the Children in Focus (CiF) subgroup of a large population-based birth cohort study (the Avon Longitudinal Study of Parents and Children) to investigate whether total immunoglobulin E (IgE) measured at 12 and 18 months could predict subsequent development of atopy at 5 yr of age. Atopy was determined by positive skin prick test (> or = 3 mm wheal) to one or more of 14 inhalant and food allergens. Prevalence of skin prick positivity to any allergen was 14.5% (104 of 715; 95% CI: 12.0-17.1%). Total IgE levels were significantly higher at 12 months of age (p < 0.0005) but not 18 months of age in those children subsequently atopic. The highest positive predictive value was 41% with an IgE measurement of >51 kU/l, with a sensitivity of 13.5% and a specificity of 95.8%. Although significant differences in early life IgE measurements were seen, the extent of overlap was great, such that the overall performance of IgE at 12 months as a screening test for atopy was poor.

Child, Preschool↗

Early nutrition and immunity - progress and perspectives.

The immune system exists to protect the host against pathogenic organisms and highly complex pathways of recognition, response, elimination and memory have evolved in order to fulfil this role. The immune system also acts to ensure tolerance to 'self', to food and other environmental components, and to commensal bacteria. A breakdown in the tolerogenic pathways can also lead to inflammatory diseases. The prevalence of inflammatory diseases, including atopic disorders, has increased over the last 60 years. The development of tolerance is the result of active immune mechanisms and both development and maintenance of tolerance are lifelong processes which start very early in life, even prenatally. Profound immunologic changes occur during pregnancy, involving a polarization of T helper (Th) cells towards a dominance of Th2 and regulatory T cell effector responses in both mother and fetus. This situation is important to maintain pregnancy through avoidance of the rejection of the immunologically incompatible fetus. During the third trimester of human pregnancy, fetal T cells are able to mount antigen-specific responses to environmental and food-derived antigens and antigen-specific T cells are detectable in cord blood in virtually all newborns indicating in utero sensitization. If the neonatal immune system is not able to down-regulate the pre-existing Th2 dominance effectively then an allergic phenotype may develop. Changes occur at, and soon after, birth in order that the immune system of the neonate becomes competent and functional and that the gut becomes colonized with bacteria. Exposure to bacteria during birth and from the mother's skin and the provision of immunologic factors in breast milk are amongst the key events that promote maturation of the infant's gut and gut-associated and systemic immune systems. The introduction of formula and of solid foods exposes the infant to novel food antigens and also affects the gut flora. Nutrition may be the source of antigens to which the immune system must become tolerant, provide factors, including nutrients, that themselves might modulate immune maturation and responses, and provide factors that influence intestinal flora, which in turn will affect antigen exposure, immune maturation and immune responses. Through these mechanisms it is possible that nutrition early in life might affect later immune competence, the ability to mount an appropriate immune response upon infection, the ability to develop a tolerogenic response to 'self' and to benign environmental antigens, and the development of immunologic disorders. A Workshop held in February 2006 considered recent findings in the areas of oral tolerance, routes of sensitization to allergens and factors affecting the development of atopic disease; factors influencing the maturation of dendritic cells and the development of regulatory T cells; the influence of gut microflora on immunity, allergic sensitization and infectious disease; the role of nutrition in preventing necrotizing enterocolitis in an animal model of preterm birth; and the role of PUFA of different classes in influencing immune responses and in shaping the development of atopic disease. This report summarizes the content of the lectures and the subsequent discussions.

Animals↗

Diagnosing peanut allergy with skin prick and specific IgE testing.

BACKGROUND: Food allergy is common in childhood. It has been suggested that the magnitude of a skin prick test or specific IgE result can improve diagnostic usefulness, but this has been addressed in only a few tertiary challenge-based studies. OBJECTIVE: To determine the predictive value of a wheal > or = 8 mm or serum specific IgE > or = 15 kU A /L for clinical allergy and investigate whether results are generalizable. METHODS: All subjects, up to 16 years of age, who had been investigated with a peanut or tree nut food challenge were eligible for the study. Subjects were referred from either a tertiary allergy clinic or a community birth cohort. All subjects with a history suggestive of food allergy were offered a challenge unless there were features of anaphylaxis. Details of challenges were prospectively recorded. Results were modeled by using logistic regression. RESULTS: There was a total of 161 peanut challenges. Recent skin prick (longest wheal diameter) and specific IgE data were available for 135 and 136 challenges, respectively. The results suggest that a skin prick result > or = 8 mm and a specific IgE > or = 15 kU A /L have predictive values of 95% (95% CI, 76.2% to 99.9%) and 92.0% (74.0% to 99.0%), respectively, for a positive challenge. Age, the type of nut, and referral pattern of the subject did not appear to alter this relationship. CONCLUSION: These data suggest that a skin prick result > or = 8 mm or a specific IgE > or = 15 kU A /L have a high predictive value for clinical allergy to peanut and that these cutoff figures appear generalizable to different populations of children undergoing an assessment for peanut allergy.

Adolescent↗

Medical treatment for rhinosinusitis associated with adenoidal hypertrophy in children: an evaluation of clinical response and changes on magnetic resonance imaging.

OBJECTIVES: The association between adenoidal hypertrophy and rhinosinusitis with upper airway inflammation is increasingly recognized; however, no study has used magnetic resonance imaging (MRI) to assess the changes in adenoid size after medical treatment of rhinosinusitis. METHODS: Thirteen children referred to a tertiary allergy clinic with symptoms of rhinosinusitis received medical treatment over a 4-month period. All underwent MRI before and after treatment. The medical treatment regimen comprised a short course of oral antibiotics and oral steroids and a longer course of oral antihistamines and intranasal steroids. RESULTS: The pretreatment MRI demonstrated enlarged adenoids and rhinosinusitis in all 13 children, with evidence of extensive rhinosinusitis in 9 of the 13. The treatment resulted in an improvement in overall symptom score; the most significant improvement was seen in mouth breathing. The posttreatment MRI showed a statistically significant reduction in adenoid size and adenoid/nasopharynx ratio, which was associated with a significant decrease in sinus involvement on MRI. CONCLUSIONS: There is a high association between adenoidal hypertrophy and rhinosinusitis in the context of an allergy clinic. Magnetic resonance imaging can document the changes in adenoid size associated with resolution of rhinosinusitis. Further studies are necessary to validate these pilot data and further assess the effects of medical treatment and the role of MRI in adenoidal hypertrophy.

Adenoids↗

Reduced eosinophil pro-fibrogenic effect in severe childhood asthma compared to mild disease: an effect of corticosteroids?

Eosinophils play an important role in inflammation and probably in airway remodeling in asthma. We previously demonstrated that eosinophils from atopic subjects display pro-fibrogenic properties towards lung fibroblasts partially by preformed transforming growth factor-beta (TGF-beta). We hypothesized that the pro-fibrogenic potential of eosinophils is increased in children with life-threatening asthma (LTA). Six children with atopic LTA clinically well-controlled by inhaled corticosteroids (ICS) and 5 children with atopic mild asthma (MA) treated only with inhaled beta(2)-agonists were investigated. The effects of their peripheral blood eosinophils on fibroblast proliferation and lattice contraction were investigated. In addition, TGF-beta(1) and IL-6 eosinophil content were also evaluated. Unexpectedly, eosinophils from LTA increased fibroblast proliferation (5.4-fold) and gel contraction (1.1-fold) significantly less than those from MA. TGF-beta(1) but not IL-6 eosinophil content in LTA was significantly lower than that in MA (2.7-fold). In vitro, addition of dexamethasone on eosinophils stimulated by mast cells resulted in a marked decrease in their TGF-beta(1) content by 1.6-fold. In conclusion, eosinophils from children with ICS-treated LTA displayed significantly less pro-fibrogenic properties than those from MA treated only with beta(2)-agonists. Our data suggest that the pro-fibrogenic effect of eosinophils might be influenced by treatment with ICS in childhood asthma.

Acetates↗

Preventing food allergy.

In this review, we examine the critical periods of immune development and how these might be modified to prevent food allergy. The relevant dietary intervention studies, roles of microorganisms and their products, and other strategies are critically analyzed. Additionally, we highlight the potential importance of different routes of allergic sensitization and the role of oral tolerance induction in the pathogenesis and prevention of food allergy.

Breast Feeding↗

Factors associated with the development of peanut allergy in childhood.

BACKGROUND: The prevalence of peanut allergy appears to have increased in recent decades. Other than a family history of peanut allergy and the presence of atopy, there are no known risk factors. METHODS: We used data from the Avon Longitudinal Study of Parents and Children, a geographically defined cohort study of 13,971 preschool children, to identify those with a convincing history of peanut allergy and the subgroup that reacted to a double-blind peanut challenge. We first prospectively collected data on the whole cohort and then collected detailed information retrospectively by interview from the parents of children with peanut reactions and of children from two groups of controls (a random sample from the cohort and a group of children whose mothers had a history of eczema and who had had eczema themselves in the first six months of life). RESULTS: Forty-nine children had a history of peanut allergy; peanut allergy was confirmed by peanut challenge in 23 of 36 children tested. There was no evidence of prenatal sensitization from the maternal diet, and peanut-specific IgE was not detectable in the cord blood. Peanut allergy was independently associated with intake of soy milk or soy formula (odds ratio, 2.6; 95 percent confidence interval, 1.3 to 5.2), rash over joints and skin creases (odds ratio, 2.6; 95 percent confidence interval, 1.4 to 5.0), and oozing, crusted rash (odds ratio, 5.2; 95 percent confidence interval, 2.7 to 10.2). Analysis of interview data showed a significant independent relation of peanut allergy with the use of skin preparations containing peanut oil (odds ratio, 6.8; 95 percent confidence interval, 1.4 to 32.9). CONCLUSIONS: Sensitization to peanut protein may occur in children through the application of peanut oil to inflamed skin. The association with soy protein could arise from cross-sensitization through common epitopes. Confirmation of these risk factors in future studies could lead to new strategies to prevent sensitization in infants who are at risk for subsequent peanut allergy.

Arachis↗

Food allergy and asthma--what is the link?

Food allergy and asthma are both atopic diseases and therefore frequently co-exist. Food allergy is common in childhood, affecting approximately 8% of infants. The diagnosis is based on a suggestive history supported by skin-prick testing, serum specific IgE or food challenge. The role of diet in the aetiology of asthma and as a precipitant of exacerbations has been investigated extensively. Many people perceive diet as being an important precipitant of their asthma but objective testing suggests that it is only important in a minority. Meanwhile, there is considerable epidemiological evidence to suggest that there is a link between asthma and food allergy. Food can induce bronchospasm and food allergy has been implicated as a risk factor for life-threatening asthma. Additionally, asthma also seems to be a risk factor for life-threatening food allergy. The mechanism underlying this connection is unclear. The co-existence of food allergy should be considered in any child with asthma. Where food allergy is confirmed, steps should be taken to avoid these foods as this may considerably improve asthma control.

Asthma↗

Development of a quality-of-life assessment for the allergic child or teenager with multisystem allergic disease.

BACKGROUND: Health-related quality of life (HRQOL) questionnaires currently being used to evaluate allergic disease are organ-specific. They therefore fail to take account of the systemic aspects of allergic disease. OBJECTIVE: To develop and validate a pediatric HRQOL questionnaire for allergic disease (Pediatric Allergic Disease Quality of Life Questionnaire, PADQLQ) that encapsulates problems related to the eyes, ears, nose, lungs, skin, emotions, and everyday activities. METHODS: In the development phase, 77 subjects (6 to 16 years of age), with seasonal or perennial allergic problems, were asked how much they were bothered by each different area of HRQOL impairment. The highest scoring areas were used to construct the PADQLQ. In the validation phase of the study, 36 subjects (8 to 16 years of age) with seasonal allergic rhinoconjunctivitis, seasonal allergic asthma, and/or cutaneous manifestations of grass pollen allergy were assessed before and during the pollen season. RESULTS: The PADQLQ contains 26 questions. In addition to standard symptoms (eg, rhinitis), it incorporates multiorgan symptoms that are usually overlooked (eg, hearing problems). The PADQLQ demonstrated good cross-sectional and longitudinal validity, showing a high degree of correlation with symptom scores and quality of life as measured by a visual analogue scale and two-organ specific questionnaires. The PADQLQ showed good within-subject reliability and a small minimal important difference (0.33; 95% CI, 0.11 to 0.54 on a 7-point scale). CONCLUSIONS: The PADQLQ has good cross-sectional and longitudinal validity, making it a potentially useful outcome measure in the evaluation of systemic treatments such as antihistamine medications and immunotherapy in children with multisystem allergic disease.

Adolescent↗

Food allergy as a risk factor for life-threatening asthma in childhood: a case-controlled study.

BACKGROUND: No objective clinical risk factors exist for pediatric life-threatening asthma. OBJECTIVES: In this study, we address whether persistent food allergy and degree of atopy are risk factors for life-threatening asthma. METHODS: By use of a case-controlled design, children (1-16 years) ventilated for an exacerbation of asthma were enrolled. Each case was matched by sex, age, and ethnicity, with 2 controls who had attended with a non-life-threatening exacerbation. All subjects were assessed by means of a questionnaire, spirometry, and skin prick or RAST testing. The data were analyzed by conditional logistic regression. RESULTS: Nineteen cases and 38 controls were enrolled. Compared with controls, cases were found to have the following risk factors: food allergy (odds ratio, 8.58; 95% CI, 1.85-39.71), multiple allergic diagnoses (4.42; 1.17-16.71), early onset of asthma (6.48; 1.36-30.85), and frequent admissions (14.2; 1.77-113.59). After regression analysis, only frequent admission with asthma (9.85; 1.04-93.27) and food allergy (5.89; 1.06-32.61) were independently associated with life-threatening asthma. Half the cases had food allergy compared with only 10% of controls. CONCLUSION: This study demonstrates that poorly controlled asthma and food allergy are significant risk factors for life-threatening asthma. More intensive management of this high-risk group of children might help to reduce future morbidity and mortality.

Adolescent↗

Relevance of inhalational exposure to food allergens.

PURPOSE OF REVIEW: This review discusses the inhalational route as a clinically important route of exposure to food allergens. RECENT FINDINGS: In childhood, we have recently demonstrated that food allergens can induce both early and late phase bronchial reactions within blinded, placebo-controlled challenges. Additionally, clinically important levels of food allergens have been measured in environmental air samples. SUMMARY: It is well known that the ingestion of food allergens frequently causes respiratory symptoms and that the mechanism of death in fatal anaphylaxis is usually profound bronchospasm. The mechanism by which ingested food allergens induce bronchial reactions is unclear. There are many case reports of bronchial reactions to aerosolized food allergens. Within the food industry the problems have been examined more systematically. From such work it is possible to gain an impression of the potential prevalence of the problem. With 10% of adult asthma being occupational and 10% of occupational asthma being induced by aerosolized food, inhalational exposure to food allergens plays a major role in at least 1% of adult asthma. For a patient with co-existent food allergy and asthma it is important that both dietary and environmental avoidance be practised. The similar pathophysiology of allergic and occupational asthma and the ability of inhaled food allergens to cause the latter raises the question as to whether aerosolized food could play a role in the pathogenesis of childhood asthma.

Allergens↗

Characterization of lymphocyte responses to peanuts in normal children, peanut-allergic children, and allergic children who acquired tolerance to peanuts.

Comparing lymphocyte responses to allergenic and nonallergenic foods could reveal the differences between pathogenic and normal immune responses to foods. Defining the cytokine-producing phenotypes of peanut-specific lymphocytes from peanut-allergic children, children who outgrew peanut allergy, and children who have always tolerated peanuts may be useful for understanding the mechanisms of food tolerance. Investigating immune responses against foods is hindered, however, by the fact that circulating food antigen-specific lymphocytes are very rare. In a novel approach we used carboxyfluorescein succinimidyl ester to detect peanut-specific lymphocytes by flow cytometry. We confirmed that these cells are indeed peanut specific by cloning. Peanut-allergic donors show Th2 polarization of cytokine production by peanut-specific cells (IFN-gamma (low), TNF-alpha (low), IL-4 (high), IL-5 (high), IL-13 (high)). Conversely, nonallergic children and children who have outgrown their allergy show Th1 skewing to peanut antigens (IFN-gamma(high), TNF-alpha (high), IL-4 (low), IL-5 (low), IL-13(low)), similarly to nonallergenic food antigens (beta-lactoglobulin, OVA). This finding suggests that peanut antigens do not intrinsically induce Th2 skewing, but that the type of response depends upon the donor's allergic status. In conclusion, food allergic status is characterized by a Th2 response whereas Th1-skewed responses underlie oral tolerance.

Adolescent↗

Clinical risk assessment of GM foods.

The main concerns about adverse effects of genetically modified (GM) foods on health are the transfer of antibiotic resistance, toxicity and allergenicity. There are two issues from an allergic standpoint. First, the transfer of a known allergen may occur from a crop into a non-allergenic target crop. The second scenario is the creation of a neo-allergen where de novo sensitisation occurs in the population. The first scenario occurred in 1996 when the 2S albumen protein from Brazil nut was transferred into soy bean (N. Engl. J. Med. 334 (1996) 688). 2S albumen was found to be a major Brazil nut allergen and the newly expressed protein in transgenic soy retained its allergenicity. Patients allergic to Brazil nuts and not to soy bean now showed an IgE mediated response towards GM soy bean. We argue that it is possible to prevent such occurrences by doing IgE-binding studies and taking into account physico-chemical characteristics of proteins and referring to known allergen databases. The second possible scenario of de novo sensitisation does not easily lend itself to risk assessment. We compare GM technology to traditional plant breeding and food processing methods. There is no evidence that the technology used for the production of GM foods poses an allergic threat per se compared to other methodologies widely accepted in the food industry. We need to proceed cautiously in the future, assessing individual GM foods on the basis of their individual merits and risks prior to introducing them into the market.

Allergens↗

Factors affecting the determination of threshold doses for allergenic foods: how much is too much?

BACKGROUND: Ingestion of small amounts of an offending food can elicit adverse reactions in individuals with IgE-mediated food allergies. The threshold dose for provocation of such reactions is often considered to be zero. However, because of various practical limitations in food production and processing, foods may occasionally contain trace residues of the offending food. Are these very low, residual quantities hazardous to allergic consumers? How much of the offending food is too much? Very little quantitative information exists to allow any risk assessments to be conducted by the food industry. OBJECTIVE: We sought to determine whether the quality and quantity of existing clinical data on threshold doses for commonly allergenic foods were sufficient to allow consensus to be reached on establishment of threshold doses for specific foods. METHODS: In September 1999, 12 clinical allergists and other interested parties were invited to participate in a roundtable conference to share existing data on threshold doses and to discuss clinical approaches that would allow the acquisition of that information. RESULTS: Considerable data were identified in clinical files relating to the threshold doses for peanut, cows' milk, and egg; limited data were available for other foods, such as fish and mustard. CONCLUSIONS: Because these data were often obtained by means of different protocols, the estimation of a threshold dose was very difficult. Development of a standardized protocol for clinical experiments to allow determination of the threshold dose is needed.

Allergens↗