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Cord blood levels of immunoglobulin G subclass antibodies to food and inhalant allergens in relation to maternal atopy and the development of atopic disease during the first 8 years of life.

BACKGROUND: Factors that either protect from or enhance the development of atopic disease appear to be acting early in life. The gestational environment, including maternal immune responses, such as transplacentally transferred immunoglobulin (Ig) G antibodies to allergens, may be of importance in this respect, since allergen-specific immunity has been demonstrated to develop in utero. OBJECTIVE: To evaluate the relation between cord blood IgG subclass antibodies to allergens, maternal atopy and development of atopic disease in the children. MATERIAL AND METHODS: The study group comprised a cohort of 96 children participating in a prospective study up to 8 years of age. Cord blood IgG subclass antibodies to ovalbumin, beta-lactoglobulin, Bet v 1 and cat dander were analysed by ELISA. RESULTS: The levels of all IgG subclass antibodies to ovalbumin and rBet v 1 were higher in newborn infants with an atopic mother, as compared with babies with nonatopic mothers. IgG1 antibody levels to cat and IgG4 antibody levels to beta-lactoglobulin and cat were also higher in atopic than in nonatopic mothers, whereas the other subclass antibody levels to those allergens were similar. High levels of cord blood IgG antibodies to cat and birch, but not to the food allergens, were associated with less atopic symptoms in the children during the first 8 years of life. Moreover, children who developed IgE antibodies to cat had lower levels of IgG antibodies to that allergen at birth. CONCLUSIONS: High levels of cord blood IgG subclass, especially IgG4, antibodies to food and inhalant allergens are associated with maternal atopy. High levels of IgG antibodies to inhalant, but not food, allergens are associated with less development of atopy in the children.

Administration, Inhalation↗

The release of histamine is associated with the inactivation of mast cell chymase during immediate allergic wheal reaction in the skin.

BACKGROUND: Chymase released by mast cells can participate in the immediate allergic wheal. However, chymase may be susceptible to inactivation by protease inhibitors during degranulation. OBJECTIVE: To study the inactivation of chymase and the release of histamine in the immediate allergic wheal reaction. METHODS: Ten sensitive atopic subjects were prick-tested with the cow dander allergen, and skin biopsies were taken from the control skin and from the challenge site at 30 and 120 min. Tryptase (Tact) and chymase (Cact) activities in mast cells were measured enzyme-histochemically. Sequential double-staining was used to demonstrate the activity and immunoreactivity (Cprot) of chymase in the same mast cell as well as alpha1-proteinase inhibitor (alpha1-PI) and alpha1-antichymotrypsin (alpha1-AC) in Tact+ cells. Skin microdialysis was used to monitor histamine release after the allergen challenge for up to 120 min RESULTS: The numbers of Tact+ and Cact+ cells were already maximally decreased at 30 min by 37 +/- 17% and 61 +/- 31%, respectively (mean +/- SD, P < 0.0001). At the same time the Cact+/Cprot+ ratio decreased from 82 +/- 15% to 43 +/- 16% (P < 0.0001). The cumulative histamine release at 30 min correlated negatively with the Cact+/Tact+ (P = 0.047) and Cact+/Cprot+ (P = 0.024) ratios, but positively with the decrease in the number of Cact+ cells (P = 0.024). These data indicate that the higher the histamine release the lower the chymase activity. Also the number of Tact+ cells in the control skin correlated positively with the cumulative histamine release at 120 min (P = 0.043). In the control skin, 95 +/- 6% and 76 +/- 8% of the Tact+ cells displayed alpha1-AC and alpha1-PI, respectively. CONCLUSION: In addition to extensive degranulation of mast cells, chymase is also rapidly inactivated after the allergen challenge, possibly by pre-existing chymase inhibitors in the mast cells. This inactivation is associated with the release of histamine.

Adult↗

Molecular cloning, expression and modelling of cat allergen, cystatin (Fel d 3), a cysteine protease inhibitor.

BACKGROUND: Cats are an important source of indoor allergens. However, only two cat allergens, Fel d 1 and albumin, have been cloned and sequenced. IgE antibodies to Fel d 1 and albumin do not fully account for IgE responses to cat and there is good immunochemical evidence that cats produce other allergens. OBJECTIVE: To identify and define the molecular structure of the other potential cat allergens. METHODS: A cat skin cDNA library was screened using pooled serum obtained from five asthmatic patients which contained high levels of IgE antibody to cat dander. Selected cDNA clones were screened by plaque immunoassay and one cDNA clone, encoding cystatin, was expressed in E. coli. The three dimensional structure of cat cystatin was modelled using the SWISS-MODEL computer program. RESULTS: Three positive cDNA clones (A, B and C) were identified, two of which were fully sequenced. Clones A and C encoded the same 98 amino acid residue sequence which showed 79% and 75% homology with bovine and human cystatin A, respectively. The cat cystatin sequence contained the conserved cysteine protease inhibitor signature and two of three lipocalin motifs. By plaque immunoassay, 60-90% of cat allergic sera had IgE ab to the expressed cystatin clones. The cysteine protease inhibitor motif was also partially conserved in dog allergen sequences, Can f 1 and Can f 2, which are lipocalins. The recombinant protein was expressed in E. coli as an 11-kDa protein, corresponding to the predicted MW of cat cystatin. The three-dimensional structure of cat cystatin was modelled on human cystatin structures. CONCLUSION: A newly identified allergen, cystatin (Fel d 3), has been cloned from cat skin and is a member of the cysteine protease inhibitor family.

Allergens↗

Familial and environmental determinants for wheezing and asthma in a case-control study of school children in Palestine.

BACKGROUND: Our prevalence study on Palestinian school children aged 6-12 years showed lower rates for asthma and asthma symptoms than economically developed and industrialized countries. Reasons for such differences are largely unknown, and could possibly be related to different environmental and lifestyle factors. OBJECTIVE: To investigate familial, early life exposures and indoor environmental determinants for asthma in children in Palestine. METHODS: From the population of our previous study, a group of 273 children with wheeze in the past 12 months (of whom 99 children had physician-diagnosed asthma) were matched with an equal number of non-wheezing controls. This case-control study involved a parental questionnaire; skin prick testing (SPT) with mixed house dust mites, cat and dog dander, mixed grass, mixed trees pollen, Alternaria tenuis, olive tree and cockroach extracts; and serum for total and specific IgE for the same eight allergens. RESULTS: Paternal asthma and maternal hayfever significantly tripled the risk for their children to have wheezing. Previous diagnoses of bronchial allergy, bronchitis, pneumonia, or whooping cough, and positive SPT for house dust mites and cockroaches were significantly more likely among wheezing and asthmatic children than controls. Specific IgE levels for house dust mites and cat allergens showed significantly higher risk for reported wheezing. After adjustment for several environmental and sociodemographic factors using multivariate logistic regression analysis, paternal asthma, maternal hayfever, damp houses, cat and cockroach SPT positivity proved to be strong predictors for wheezing symptoms. CONCLUSION: Our study confirmed that familial 'atopic' diseases are significant predictors of childhood asthma in Palestinian children. Moreover, indoor environment such as presence of cats and domestic moulds also appear to play a role. Our findings are consistent with studies in Canada, New Zealand, Estonia and Sweden, and show promise to explore further gene-environment interaction in the genesis of asthma.

Air Pollution, Indoor↗

Usefulness of specific immunotherapy in patients with severe perennial allergic rhinitis induced by house dust mite: a double-blind, randomized, placebo-controlled trial.

OBJECTIVES: To evaluate the effectiveness of specific immunotherapy (SIT) in patients with severe house dust mite (HDM)-induced perennial allergic rhinitis using diary cards and objective endpoints. PATIENTS AND METHODS: Thirty-six adult patients were selected with moderate to severe allergic rhinitis due to HDM allergy uncontrolled by regular anti-allergic drugs. Twenty-eight patients completed the study, 22 of these patients also had mild asthma. Subjects were stratified for HDM sensitivity on the basis of their 4-week diary card score and the size of their immediate and late-phase skin reaction to HDM. The groups were well matched for all relevant parameters. Patients were randomized to receive active preparation (Alutard(R)-SQ, ALK, Dermatophagoides pteronyssinus extract) or an identical placebo preparation. Increasing doses were administered until the maintenance dose was reached. This dose was then given once a month for 12 months. RESULTS: Clinical efficacy was evaluated by symptom medication diary cards recorded for 4 weeks after 12 months of continuous treatment and compared with pre-treatment scores. Skin test reactivity was re-measured after 12 months of treatment to HDM, cat dander and codeine phosphate. After 1 year of treatment, the actively treated group showed a 58% reduction in diary card symptom scores (P<0.002) and a 20% reduction in the use of rescue medication. The placebo group had a 32% reduction in symptom scores (P=NS), but no reduction in rescue medication requirements. The active group showed 36% reduction in skin prick test sensitivity to D. pteronyssinus (P=0.006), while the placebo group values were unchanged. Skin reactivity to codeine was unchanged in both groups. No significant adverse reactions to SIT were encountered. CONCLUSIONS: One year of SIT for D. pteronyssinus in patients with poorly controlled rhinitis (+/-mild asthma) produced clinically useful improvement as shown by symptom-medication diary cards and reductions in immediate skin reactions compared with placebo treatment.

Adult↗

Allergic sensitization among adults in Tallinn, Estonia.

BACKGROUND: The prevalence of allergic sensitization has increased worldwide during recent years. OBJECTIVE: The aim of the study was to estimate the prevalence of allergic sensitization and to evaluate the influence of age, gender, number of siblings, pet keeping in childhood, and residential area before the age of five on allergic sensitization among adolescents and adults aged 17-66 years in the capital of Estonia, Tallinn. A cross-sectional study was carried out between March 1997 and December 1998. METHODS: The sensitization to 15 inhalant allergens was assessed. The associations between sensitization based on skin prick tests (SPTs), symptoms based on a structured interview, and possible risk factors were estimated. A random sample of 516 subjects was included in the study analysis. RESULTS: The prevalence of allergic sensitization was 34.5%, while it was 39.3% in subjects aged 20-44 years. The most prevalent sensitization was against the German cockroach, 15.5%, and it was particularly high among adolescents. It was followed by mugwort, dog, two storage mites species, and cat dander. Subjects with wheezing during the last 12 months, attacks of shortness of breath, wheezing due to furred animals, and allergic rhinitis or conjunctivitis had a significantly higher prevalence of positive SPT. CONCLUSION: We found a surprisingly high prevalence of allergic sensitization among adults in Tallinn. Our results suggest that the cockroach allergen should be included in the investigation panel in order to reach a true prevalence of allergic sensitization in Estonia. Further, the pattern of allergic sensitization in Estonia appears to be different from published data about allergic sensitization in Scandinavia.

Adolescent↗

Sensitization to fungi: epidemiology, comparative skin tests, and IgE reactivity of fungal extracts.

BACKGROUND: Several fungal species are known to cause severe respiratory and cutaneous allergic diseases. Extracts from several allergenic fungi are used for in vivo and in vitro tests, as standard preparations are still not available. OBJECTIVE: The aims are to define the pattern of in vivo and in vitro IgE reactivity to fungal species in an allergic population with respiratory symptoms; to determine the influence of different extract preparations on diagnostic results; and to evaluate whether there exists a relationship between the diagnostic pattern of reactivity and the pattern of specific IgE reactivity in immunoblots. METHODS: Skin prick tests were applied to a cohort of 4962 respiratory subjects, aged 3-80 years. Fungal extracts from Alternaria, Aspergillus, Candida, Cladosporium, Penicillium, Saccharomyces, and Trichophyton were used, along with extracts from pollens, mites, and animal dander. Demographical and diagnostic data were recorded. IgE detection was carried out with the same allergenic extracts plus Malassezia. Comparative skin tests and IgE detection were carried out using extracts from three commercial suppliers. IgE immunoblots were carried out with the same panel of commercial fungal extracts and were compared with in-house extracts. Data analysis was carried out by grouping the population on the basis of their reactivity to a single, to two or to more than two, mould species. RESULTS: Nineteen percent of the allergic population reacted to at least one fungal extract by means of the skin test. Alternaria and Candida accounted for the largest number of positive tests, and along with Trichophyton they were the main sensitizers in the subset of patients with an isolated sensitization. The prevalence of skin test reactivity increased for these three fungi in the subsets with two associated reactivities and, furthermore, in the subset showing reactivity to more than two mould species. In the latter group, a steady increase of the skin test reactivity was recorded for all the other fungal sources, suggesting a clustered reactivity. Comparative skin and IgE testing with different groups of subjects with a simple pattern of skin reactivity resulted in sensitivity differences between in vivo and in vitro tests, whereas discrepant results were recorded in the subsets of patients with multiple fungi sensitization. Although hampered by the limited reliability of fungal extracts, IgE immunoblots revealed differing patterns of reactivity when sera from the three subsets were used. This suggests a link between the diagnostic reactivity pattern and the IgE sensitization to extracts' components. Age and gender distribution differed among the Alternaria-, Candida-, and Trichophyton-sensitized subjects, but not in the subset with more than two fungi sensitizations. CONCLUSIONS: The preliminary assessment of a new classification of the mould-sensitized population has been reached. The limiting quality of fungal extracts requires future studies using an allergenic molecule-based approach. The diagnostic process and the definition of the reactivity pattern would thus be easy, and it could lead to a novel specific immunotherapy approach.

Adolescent↗

The major dog allergens, Can f 1 and Can f 2, are salivary lipocalin proteins: cloning and immunological characterization of the recombinant forms.

Canis familiaris allergen 1 (Can f 1) and Canis familiaris allergen 2 (Can f 2) are the two major allergens present in dog dander extracts. We now report the isolation of cDNAs encoding both proteins and present their nucleotide and deduced amino acid sequences. Can f 1, produced by tongue epithelial tissue, has homology with the von Ebner's gland (VEG) protein, a salivary protein not previously thought to have allergenic properties. Can f 2, produced by tongue and parotid gland, has homology with mouse urinary protein (MUP), a known allergen. Both VEG protein and MUP are members of the lipocalin family of small ligand-binding proteins. Recombinant forms of Can f 1 and Can f 2 were produced and tested for immunoglobulin E (IgE) reactivity. Among dog-allergic subjects, 45% had IgE directed exclusively to rCan f 1, and 25% had IgE to both rCan f 1 and rCan f 2. In addition, both recombinant proteins were able to cross-link IgE and elicit histamine release from peripheral blood leucocytes in vitro. These findings confirm that Can f 1 and Can f 2 are major and minor dog allergens, respectively, and demonstrate that recombinant forms of dog allergens retain at least some IgE-binding epitopes.

Allergens↗

Skin prick testing in general practice: a pilot study.

Allergy skin prick testing is regarded as a routine diagnostic procedure in hospital settings, but its role in general practice is not yet defined. Our aim was to explore the ways in which skin prick testing might facilitate the work of general practice nurses engaged in asthma patient care. A structured questionnaire was completed by 18 practice nurses before and again after administering allergy skin tests to four common aeroallergens (dust mite, grass pollen, cat and dog danders) to 319 consecutive attenders with known or suspected asthma. Nurses' decisions about whether or not to give allergen avoidance advice were reversed after skin testing in 63 (22%) cases for dust mite, 67 (23%) cases for grass pollen, 38 (13%) cases for cat fur and 49 (17%) cases for dog hair. Had allergen avoidance interventions been targeted only at patients with both a positive skin test and a positive clinical history, the number of planned interventions would have declined from 305 before skin testing to 142 after. The findings suggest that allergy skin prick testing was feasible and acceptable in general practice, and that one role may be to reduce the number of allergen avoidance interventions offered to patients unlikely to benefit.

Adolescent↗

Biochemical characterization and surfactant properties of horse allergens.

A new allergen from horse dander, Equ c 5 has been purified. Its biochemical and biophysical properties have been characterized and compared with those of Equ c 1, Equ c 2 and Equ c 4. Their molecular masses, determined by mass spectrometry, were 22 kDa for Equ c 1, 16 kDa for Equ c 2, 18.7 kDa for Equ c 4 and 16.7 kDa for Equ c 5. Their pI values were between 3.8 and 5.25. Equ c 2 and Equ c 5 are not glycosylated, while Equ c 4 contains a tri-antennary tri-sialylated N-linked glycan. Linkages of terminal N-acetylneuraminic acid to galactose were: alpha-(2-->6) in Equ c 4, and both alpha-(2-->3) and alpha-(2-->6) in Equ c 1. Oligosaccharide portions of Equ c 1 or Equ c 4 were barely involved in IgE-immunoreactivity. Partial N-terminal sequence of Equ c 4 shares a significant sequence homology with the rat submandibular gland protein A. No matching was found for two internal peptides of Equ c 5. Surfactant properties of horse allergens as well as other proteins were investigated. In contrast to Equ c 2 and Equ c 3, solutions of Equ c 1, Equ c 4 and Equ c 5 significantly lowered the surface tension. Relationship between a property such as this, involving oriented hydrophobic patches of a molecule and allergenicity, is addressed.

Allergens↗

[Farmers' children suffer less from hay fever and asthma].

BACKGROUND: Farm children suffer less frequently from pollinosis and bronchial asthma, although they are exposed to higher concentrations of airborne allergens. How do farm children differ from children in the general population with respect to immunological sensitization to airborne allergens? METHODS: Since 1983, a continuing seroepidemiological study of allergic reactions of schoolchildren in a rural area was conducted. Each year, all 15 year-old schoolchildren were given a standardized allergy questionnaire and are tested serologically (RAST/CAP-test) for their IgE sensitization towards the four major groups of airborne allergens: timothy grass pollen, birch pollen, house-dust mites, and cat dander. Farm children were compared with children who only occasionally help out on farms and also with those who had no direct contact with agriculture. RESULTS: From a total of 1307 children, 1287 questionnaires (98.5%) and 1100 (84.2%) of the serological tests could be analysed. Over the 16 years of the study, a statistically significant increase in the incidence and severity of hay fever and asthma was found in the children with no direct contact to agriculture. This was coupled with a significant increase in the sero-prevalence of sensitisation to the major airborne allergens. Among the 133 farm children, the prevalence of hay fever was: any history of hay fever in 2.4%, hay fever within the last year in none. A history of asthma was found in 1.6% of the children. Among children who occasionally worked on or had contact with farms, the prevalences were: any history of hay fever 9.3%, hay fever within the last year 9.3%, asthma 4.4%. Corresponding prevalences in children with no direct contact to farms were 18.3%, 18.6% and 9.1%, respectively. The seroepidemiological tests showed that the farm children not only had an overall lower rate of seroprevalence of antibodies towards the 4 marker allergens, but they also became sensitized to a lesser extent. At increasing cut-off values of the specific IgE titers, the odds ratio of the farm children in comparison to the control children became increasingly significant. This trend was found with all four marker allergens. The paradoxical immune reaction of farm children towards airborne allergens shows two characteristic quantitative features: in spite of high exposure rates, the children became sensitized less often and more weakly than control classmates from the same village. Children who had intermittent contact with farms showed intermediate results with respect to both symptoms and sensitization. CONCLUSIONS: These farm children have thus become adapted towards the allergens to which they are exposed. This immunological form ist similar to results from East Germany and the former USSR, in spite of the fact that lifestyle and exposure to microbes differ greatly. The immunological adaptation can best be interpreted as the result of a greater and continual stimulation of the Th1-immune response towards anthropozoonotic antigens.

Adolescent↗

[Allergen immunotherapy - a position paper of the German society for allergology and clinical immunology].

Mechanisms of allergen immunotherapy (AIT) are complex inducing numerous immunological effects. Successful AIT is most likely based on a functional switch of and tolerance induction in specific T cells downregulating allergic hypersensitivity and inflammation. Subcutaneous AIT for allergic rhinoconjunctivitis and allergic asthma has been successfully assessed in controlled studies with several clinically important allergens (i. e. birch-, grass- and mugwortpollen, dust mites, animal dander) and has shown convincing clinical efficacy. Considered as the only causal treatment besides allergen avoidance at present, AIT can alter the natural course of allergic diseases. Hymenopteravenom hypersensitivity (to bee- and wasp venom) treated with AIT gives the best results compared to AIT with other allergens. AIT is indicated in patients with IgE-mediated sensitizations and corresponding clinical symptoms to allergens, which do not or hardly permit allergen avoidance and which are available as suitable extracts. Decisions about indication and allergen selection should only be made by a physician with certified training or qualified knowledge and skills in allergology. AIT is administered by physicians experienced in this therapy. After addressing tolerability and present status of health the recommended or individually adjusted does is injected and precisely documented, followed by a mandatory waiting period of 30 minutes. Indication for and application of AIT in children are quite similar compared to the treatment of adults. Children tolerate AIT very well and benefit especially from its immunomodulatory effects. Risk factors for and results of unwanted systemic effects can effectively be minimized by training of the staff members involved, adhering to safety standards and immediate emergency treatment. Modified allergens, recombinant proteins and immunomodulatory adjuvants created by basic research are promises for an improved efficacy of AIT with reduced unwanted effects in the future.

Allergens↗

Environmental exposure to endotoxin and its relation to asthma in school-age children.

BACKGROUND: In early life, the innate immune system can recognize both viable and nonviable parts of microorganisms. Immune activation may direct the immune response, thus conferring tolerance to allergens such as animal dander or tree and grass pollen. METHODS: Parents of children who were 6 to 13 years of age and were living in rural areas of Germany, Austria, or Switzerland where there were both farming and nonfarming households completed a standardized questionnaire on asthma and hay fever. Blood samples were obtained from the children and tested for atopic sensitization; peripheral-blood leukocytes were also harvested from the samples for testing. The levels of endotoxin in the bedding used by these children were examined in relation to clinical findings and to the cytokine-production profiles of peripheral-blood leukocytes that had been stimulated with lipopolysaccharide and staphylococcal enterotoxin B. Complete data were available for 812 children. RESULTS: Endotoxin levels in samples of dust from the child's mattress were inversely related to the occurrence of hay fever, atopic asthma, and atopic sensitization. Nonatopic wheeze was not significantly associated with the endotoxin level. Cytokine production by leukocytes (production of tumor necrosis factor alpha, interferon-gamma, interleukin-10, and interleukin-12) was inversely related to the endotoxin level in the bedding, indicating a marked down-regulation of immune responses in exposed children. CONCLUSIONS: A subject's environmental exposure to endotoxin may have a crucial role in the development of tolerance to ubiquitous allergens found in natural environments.

Adolescent↗

Autoallergy: a pathogenetic factor in atopic dermatitis?

Long before the discovery of IgE it was reported that human dander extract can elicit immediate-type skin reactions in patients with severe atopy and that this skin sensitivity can be passively transferred with serum. Several recent findings have rekindled the interest in this phenomenon and led to the concept that IgE autoreactivity may play a pathogenetic role in severe and chronic forms of atopy. The elucidation of the nature of several environmental allergens has revealed striking structural and immunologic similarities with human proteins. It was also reported that patients predominantly with severe and chronic manifestations of atopy (eg, atopic dermatitis) contain IgE autoantibodies against a wide variety of proteins expressed in histogenetically unrelated human cell types and tissue specimens. Last, complementary DNAs coding for autoallergens were isolated from human expression complementary DNA libraries and recombinant autoallergens were produced. The autoallergens characterized to date represent mainly intracellular proteins, but some of them could be detected as IgE immune complexes in sera of sensitized patients. We suggest that at least two pathomechanisms could play a role in autoallergy. First, autoallergens may cross-link effector cell-bound IgE autoantibodies and, by release of inflammatory mediators, lead to immediate-type symptoms. Second, IgE-mediated presentation of autoallergens may activate autoreactive T cells to release proinflammatory cytokines, contributing to the magnitude of the allergic tissue reaction.

Antibodies, Anti-Idiotypic↗

Recombinant allergens for diagnosis and therapy of allergic disease.

Many of the problems associated with using natural allergenic products for allergy diagnosis and treatment can be overcome with use of genetically engineered recombinant allergens. Over the past 10 years, the most important allergens from mites, pollens, animal dander, insects, and foods have been cloned, sequenced, and expressed. In many cases the three-dimensional allergen structure has been determined and B-cell and T-cell epitopes have been mapped. These studies show that allergens have diverse biologic functions (they may be enzymes, enzyme inhibitors, lipocalins, or structural proteins) and that as a rule the allergen function is unrelated to its ability to cause IgE antibody responses. High-level expression systems have been developed to produce recombinant allergens in bacteria, yeast, or insect cells. Recombinant allergens show comparable IgE antibody binding to their natural counterparts (where available) and show excellent reactivity on skin testing and in in vitro diagnostic tests. Cocktails of recombinant allergens can be formulated with predetermined and uniform allergen levels, which could replace natural allergens and result in the development of innovative, patient-based tests for allergy diagnosis. Recombinant allergens also offer the exciting possibility of developing new forms of allergen immunotherapy, including the use of hypoallergens, allergens coupled to IgE suppressive adjuvants, and peptide-based therapies. The production of recombinant allergens as defined molecular entities makes it feasible to consider the possibility of developing prophylactic allergen vaccines. The introduction of recombinant allergens in research and in clinical trials should lead to significant improvements in allergy diagnosis and treatment.

Allergens↗

The role and remediation of animal allergens in allergic diseases.

Animal allergens are common causes of both acute and chronic allergic disease. The most important animal allergens are derived from mammals, principally cats, dogs, rats, mice, horses, and cows, which secrete or excrete allergens into the environment. Allergic sensitization may occur at home or in the workplace. Cat and dog allergens commonly cause allergies in the home and affect the general population. Laboratory animal handlers often have allergic reactions to rats and mice. Cow dander allergy is usually caused by occupational exposure and occurs in farmers and farm workers. Horse allergy occurs among people who regularly handle horses, either professionally or for recreational purposes. Over the past 20 years, the major animal allergens have been defined and characterized with regard to their molecular structure, immunogenicity, and environmental distribution. One remarkable finding has been the fact that most of the mammalian allergens that have thus far been cloned belong to a single family of proteins called the lipocalins. In addition to these molecular similarities, it has also been shown that most of the animal allergens are quite similar with regard to their aerodynamic properties. Although much is yet to be learned, progress is being made in our knowledge regarding the steps that may be necessary to control exposure to these allergens through environmental modifications in both homes and occupational settings. These measures include source control, air filtration devices, barrier devices, removal of carpeting and other reservoirs, and, in some cases, washing of the animal.

Allergens↗

Allergic rhinitis: definition, epidemiology, pathophysiology, detection, and diagnosis.

Allergic rhinitis (AR) is a heterogeneous disorder that despite its high prevalence is often undiagnosed. It is characterized by one or more symptoms including sneezing, itching, nasal congestion, and rhinorrhea. Many causative agents have been linked to AR including pollens, molds, dust mites, and animal dander. Seasonal allergic rhinitis (SAR) is fairly easy to identify because of the rapid and reproducible onset and offset of symptoms in association with pollen exposure. Perennial AR is often more difficult to detect than SAR because of the overlap with sinusitis, respiratory infections, and vasomotor rhinitis. SAR can result in hyperresponsiveness to allergens such as cigarette smoke, once pollen season is over. Perennial AR is defined as occurring during approximately 9 months of the year. AR affects an estimated 20 to 40 million people in the United States alone, and the incidence is increasing; an estimated 20% of cases are SAR; 40% of cases are perennial rhinitis; and 40% of cases are mixed. The pathophysiology of SAR is complex. There is a strong genetic component to the allergic response, which is driven through mucosal infiltration and action on plasma cells, mast cells, and eosinophils. The allergic response occurs in two phases, which are considered the "early" and "late" phase responses. Early phase response occurs within minutes of exposure to the allergen and tends to produce sneezing, itching, and clear rhinorrhea; late phase response occurs 4 to 8 hours after allergen exposure and is characterized by congestion, fatigue, malaise, irritability, and possibly neurocognitive deficits. The key to diagnosis of AR is awareness of signs and symptoms. IgE antibody tests to detect specific allergens are the standard method used today; however, in addition, diagnosis must be confirmed with a positive history and demonstration that the symptoms are the result of IgE-mediated inflammation.

Adolescent↗

Risk factors for asthma in urban Ghana.

BACKGROUND: Asthma is increasing in prevalence and severity in Africa. Previous studies have suggested that the prevalence of atopy in West Africa was low. OBJECTIVE: We sought to investigate the risk factors for asthma in Ghanaian school children. METHODS: Fifty children (age range, 9-16 years) with a physician diagnosis of asthma and asthma symptoms within the previous 12 months and 50 age- and sex-matched healthy control subjects were randomly selected and evaluated by means of questionnaire, skin testing, total and specific IgE measurements, and allergen level measurements from bed dust samples (mite, cat, dog, and cockroach). RESULTS: Asthmatic children were exposed to higher levels of mite allergens than were control children (geometric mean, 19 microg/g [95% CI, 13.6-26.5] vs. 11.2 microg/g [7.4-15.7]; P <.05). Cat and dog allergen levels were low. There was a marked dissociation between skin test responses and the presence of specific IgE to cat and dog (CAP method). However, 84% of subjects with positive cat dander-specific IgE levels in cat CAP tests and negative skin test responses did not have Fel d 1-specific IgE (chimeric ELISA). In the univariate analysis significant associations with the patient group were found for sensitization to mite (odds ratio [OR], 9.3; 95% CI, 3.7-23.4) and cockroach (OR, 3.9; 95% CI, 1.3-11.6), inner-city residence (OR, 3.5; 95% CI, 1.4-8.9), asthma in family member (OR, 3.5; 95% CI, 1.4-9.0), low (<5) position in sibship (OR, 3.6; 95% CI, 1.2-11), presence of smoker in home (OR, 3.7; 95% CI, 1.2-11.9), small household size (OR, 0.57; 95% CI, 0.35-0.93), and use of electricity as domestic fuel (OR, 0.34; 95% CI, 0.12-0.97). In the multivariate analysis sensitization to mites remained the strongest risk factor associated with the asthmatic group (OR, 10.4; 95% CI, 3.5-30.9). The other significant associations were inner-city residence (OR, 4.8; 95% CI, 1.5-5.2), sensitization to cockroach (OR, 4.9; 95% CI, 1.3-18.6), and position in sibship of less than 5 (OR, 6.3; 95% CI, 1.3-29.4). CONCLUSION: Sensitization to dust mite and cockroach allergens, inner-city residence, and low position in sibship were independent risk factors for asthma in Ghanaian children.

Adolescent↗