Allergens are low-molecular-weight proteins capable of inducing IgE antibody and triggering an allergic response. For those with an atopic predisposition, exposure to these environmental allergens causes not only the immunological sensitization required for the development of atopic disease but also the provocation of acute symptoms and the maintenance of chronic symptoms. Several allergenic proteins usually are derived from any specific allergenic source (e.g., several proteins derived from grass pollen are allergenic). When a particular protein is recognized by IgE antibody from more than half of individuals allergic to the source, it is termed a major allergen. The major allergens are named with the first three letters of the genus and then the first letter of the species name followed by a group designation. Examples include Amb a 1 (Ambrosia artemisiifolia—ragweed), Lol p 1 (Lolium perenne—ryegrass); and Fel d 1 (Fells domesticus—domestic cat). For many allergenic proteins, DNA sequences are known and allergenic epitopes—sites on the protein binding IgE antibody and/or T cell receptors—have been delineated. It has become evident that allergic sensitization to particular proteins is not only related to environmental exposure but also, in part, dependent upon individual human leukocyte antigen (HLA) molecules that play a role in processing these allergens and presenting them to the immune system.
Nasal mucosal provocation tests were done on eight patients with seasonal allergic rhinitis before and after a birch pollen season. The effects on nasal microvascular blood flow were detected by means of laser Doppler flowmetry. The patients reacted to the birch pollen provocation with an increase in blood flow. This increase was greater after the pollen season than before, when the same pollen doses were used, indicating a priming phenomenon of the resistance vessels.
SummarySeveral studies have demonstrated that neuropeptides are present in peptidergic fibres of bronchial tissue. The aim of the present study was to evaluate in vivo the effect of nedocromil sodium (2 × 2 mg) on bronchospasm induced by inhalation of substance P. Six moderate asthmatic patients, mean age 25.17 years, were studied. Airway response was measured as FEV1 and the dose of substance P (using a dose range of 23–736 nmol) producing a 20% decrease in FEV1 (PD20) was calculated from the individual semilogarithmic dose‐response curves. Patients were studied on 3 separate days in a randomized, double‐blind manner. On the first day a baseline PD20 value was determined. On subsequent days substance P challenge was performed after pretreatment (20 min before challenge) with either placebo or nedocromil sodium. Student's paired t‐test and Wilcoxon's test were used for statistical analysis. The results of this study demonstrated that inhalation of substance P causes a dose‐dependent bronchoconstriction and that the bronchoconstriction induced by substance P can be prevented by pre‐treatment with nedocromil sodium.
Childhood asthma often begins in children under 3 years of age. Allergy contributes to the severity and persistence of childhood asthma so we examined the application of mixed allergen RAST discs (Paediatric Mix, a mixture of food antigens and Phadiatop, a mixture of inhalants) to the diagnosis of allergy. One hundred and nine children with a median age of 3 years, 71.6% of whom had asthma, were first assessed by one allergist who recorded their atopic status as positive, negative or questionable, on clinical grounds. Serum from each of these patients was used to determine a total IgE and 13 RAST assays. A laboratory definition of atopy was defined as a serum IgE greater than 1 standard deviation from normal, plus one or more positive RAST assays. The laboratory results influenced the assessment of atopy in 41% of cases. The use of just two mixed allergen discs (Paediatric Mix and Phadiatop) correctly assigned the presence or absence of atopy with a sensitivity of 98% and specificity of 98%, compared with the full laboratory evaluation. Very young infants were often just positive to food allergens but the Phadiatop disc could be used to suggest the onset of immunological sensitivity to inhalant antigens. Thus the application of mixed allergen RAST discs facilitated the diagnosis of atopy in young children.
SummaryConcern about side‐effects of theophylline prompted us to investigate whether this drug could be eliminated from the multi‐medication regimen of severe asthmatics. We studied patients with a demonstrated requirement for systemic steroids who were taking most other available anti‐asthma medications in an attempt to reduce systemic steroids while maintaining clinical stability. Five in‐patients, 12–15 years old, completed a double‐blind, cross‐over trial of theophylline vs placebo. All were stable for 4 weeks prior to the study with normal spirometry and mildly elevated lung volumes. Regular medications consisted of long‐acting theophylline with levels between 12 mcg/ml and 16 mcg/ml, and prednisone 10–30 mg on alternate days. In addition, they were all taking inhaled metaproterenol, cromolyn sodium, atropine sulphate, and beclomethasone dipropionate four times daily (qid). Patients received either theophylline or placebo during two drug periods. All other medications were unchanged. Parameters measured were symptom score, number of extra respiratory treatments (prn RTs), increase in steroid dosage, and daily spirometry. During the placebo period, all five patients required increased steroids, daily spirometry decreased and three patients developed severe exacerbations unrelated to viral infection. A marked increase in symptom score occurred within 48 hr of discontinuing theophylline in all. These findings emphasize that theophylline is beneficial in a subset of severe asthmatics who cannot be controlled with all other available bronchodilators, cromolyn, and inhaled and systemic steroids.
SummaryA hypothesis is presented which states that aspirin‐induced asthma results from chronic viral infection. This type of asthma has, indeed, a highly characteristic clinical course, reminiscent of viral upper respiratory tract infection. It is suggested that, in response to a virus, a long time after the initial exposure, specific cytotoxic lymphocytes are produced. Their activity is suppressed by prostaglandin E2 (PGE2) produced by pulmonary alveolar macrophages. Anti‐cyclo‐oxygenase analgesics block PGE2 production, and allow cytotoxic lymphocytes to attack and kill their target cells, i.e. the virus‐affected cells of the respiratory tract. During this reaction, toxic oxygen intermediates, lysosomal enzymes and mediators are released, which precipitate attacks of asthma. These acute attacks can be prevented by avoidance of all drugs with anti‐cyclo‐oxygenase activity, however, asthma continues to run a protracted course because of chronic viral infection.
Summary Twelve workers with hard metal asthma diagnosed on the basis of peak flow diaries and positive bronchial reactions to cobalt chloride (CoCl 2 ) were studied for sensitization by detection of specific antibodies to radioactive cobalt ( 57 Co), cobalt‐conjugated human serum albumin (Co‐HSA) and cobalt‐conjugated exchange resin (Co‐resin). Their IgE titres ranged from 73 to 1500 IU/ml and eight were atopic individuals. Sixty serum samples from asthmatic patients with IgE titres of 14–4300 IU/ml were studied as controls in all tests. Eleven of twelve subject sera that selectively bound to 57 Co after incubation with saturated ammonium sulphate (>232 c.p.m., P <0.01) were divided into three groups: (1) six sera showing evidence of specific IgE antibodies to Co‐HSA (>673 c.p.m., P <0.01) without those to Co‐resin; (2) one serum giving a positive radio‐allergosorbent test (RAST) only to Co‐resin (>417 c.p.m., P <0.01), and (3) four sera that were negative for two antigenic agents (Co‐HSA, Co‐resin). These results suggest that the subjects had occupational asthma due to hard metal exposure from cobalt sensitivity. An immuno‐allergic mechanism mediated by specific IgE antibodies to cobalt was confirmed to be responsible for the development of hard metal asthma, with the possibility of some role of the reaction without reagins.
SummaryAnamnestic and immunological data of workers of a platinum refinery (group A: workers with work‐related symptoms, n= 8; group B: workers with symptoms not clearly work‐related, n= 9; group C: asymptomatic workers, n= 13) and controls (group D: atopies, n= 10; group E: non‐atopics, n= 16) were compared. Exposure to platinum salt was higher in group A than in groups B or C. In group A, symptoms developed 4 months (median) after the onset of exposure. All subjects of group A and three workers of group B, but none of the workers of the other groups, showed a positive cutaneous reaction to (PtCl6)2−. Total serum IgE was higher in groups A and D than in groups B, C or E.(PtCl6)2−‐specific IgE was higher in group A, but there was non‐specific binding of (PtCl6)2− to IgE. Histamine release with (PtCl6)2− was found in all groups and was highest in atopic controls. Histamine release with (PtCl6)2− and histamine release with anti‐IgE showed an excellent correlation, suggesting a similar release mechanism of (PtCl6)2− and anti‐IgE. In skin‐test positive subjects, high cutaneous (PtCl6)2−‐sensitivity is linked to high histamine release with (PtCl6)2− or anti‐IgE, supporting the concept of a role of cell surface IgE or IgE‐Fc‐receptor in the release process with platinum salts. However, high specificity of cutaneous reactions contrasts with low specificity of in‐vitro tests with (PtCl6)2−. A different reaction of basophils and mast cells, when challenged with free platinum salts, is hypothesized. We conclude that neither histamine release from basophils with (PtCl6)2− nor RAST for the detection of (PtCl6)2− specific IgE are helpful in the diagnosis of platinum salt allergy.
Airborne fungi in the homes of patients with allergic rhinitis or asthma, from a Toronto Allergy Clinic population, were isolated, quantified and identified to species. Allergen extracts were prepared from sixteen of these isolated species and used for skin-prick testing of twenty-six patients. Fourteen of the total patients reacted to one or more of these extracts at 1:10 (w/v) concentrations. The most common positive skin responses (8/14 to 6/14) were found for Cladosporium cladosporioides, Alternaria tenuis, C. sphaerospermum, and Fusarium sp. The two Cladosporium species were also most commonly isolated in homes, but A. tenuis and Fusarium sp. were found only in 4% and less than 1% of the air samples, respectively. Epicoccum purpurascens and C. herbarum, which were isolated on approximately 10% of the plates, showed fewer skin reactions compared with the above. Positive skin-test response to the other ten study extracts ranged from 5/14 for two species of Aspergillus and Phoma glomerata, to 1/14 for Penicillium viridicatum; of these species, Aspergillus fumigatus was isolated in 3% of the home samples, the others were less than 1%. The findings suggest that fungal antigens from species found in homes are commonly associated with skin sensitization in an allergy clinic population with upper or lower respiratory allergy. No specific relationships were found, however, between the prevalence of fungal species in the home environment and their prevalence as skin-test allergens.
SummaryA group of thirty car painters exposed to vapours and aerosols of paint containing prepolymer and monomer of hexametylene diisocyanate (HDI) was investigated. Specific antibodies against monomer HDI and prepolymerized HDI were analysed with RAST (IgE) and ELISA (IgG) assays after conjugation of the haptens with human serum albumin. There was no significant increase of serum IgG antibodies against HDI monomer, nor of specific IgE antibodies against HDI monomer or prepolymer. Specific IgG antibodies against prepolymerized HDI were significantly increased, as compared with non‐exposed referents (medians 0.11 vs 0.03 absorbance (A)). Six car painters were found to have specific IgG antibodies of subclass 4 against HDI prepolymer, four also against HDI monomer. This shows an association between exposure and specific IgG antibodies. Thirteen subjects had suffered symptoms of rhinitis and/or conjunctivitis, and ten had symptoms from the bronchi (two asthma). There was no significant association between symptoms and levels of specific antibodies. Most of the symptoms were slight and unspecific, probably due to irritative effects of the exposure.
