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Hay fever. 2. Clinical features, diagnosis, investigation and treatment.

This is the second of two reviews of hay fever. The first article dealt with prevalence and natural history, historical background and mechanisms. This article outlines the clinical features of hay fever, examines the correlation of symptoms with pollen count and describes current views of diagnosis and investigation. History and examination, skin testing, the radio-immunosorbent test (RIST) and radio allergosorbent test (RAST) and the correlation between RAST and skin testing are described. Some consideration is given to the part played by nasal challenge tests and measurements of nasal airways resistance. The section on treatment includes some general considerations, avoidance measures, anti-histamines, nasal steroids, sodium cromoglycate, systemic steroids, nasal vasoconstrictors, hyposensitisation and eye preparations. The final section is centred on future developments.

Adrenocorticotropic Hormone↗

The effect of orally administered sodium cromoglycate on symptoms of food allergy.

A comparison was made between the effects of sodium cromoglycate (SCG) and placebo on symptoms of food allergy in twenty children. Both the clinician's and patient's preferences and the clinician's evaluation of the specific response to challenge showed a significant benefit from SCG. A striking effect on skin symptoms was seen in some children and the recorded mean score for skin symptoms was lower after 2 weeks' treatment with sodium cromoglycate. However, the differences detected from the mean symptom scores were not statistically significant. Neither were there any significant changes in the IgE, IgG, IgA and IgM food allergen antibody levels related to the treatment.

Adolescent↗

Pneumococcus-specific immunoglobulin E in cigarette smokers.

A relationship between elevated serum immunoglobulin E levels and smoking has been demonstrated in epidemiological studies. Allergy skin test data suggest that the excess immunoglobulin E of smokers is not specific for aeroallergens. It is possible that the excess immunoglobulin E is specific for microorganisms that often infect the lower respiratory tract of smokers. To investigate this possibility we utilized a radioallergosorbent test assay for detecting serum immunoglobulin E specific for Streptococcus pneumoniae, an organism commonly isolated from the respiratory tract of smokers with chronic bronchitis. We assayed sera of thirty smokers and thirty nonsmokers for immunoglobulin E specific for Streptococcus pneumoniae. Individual sera were considered positive for pneumococcus-specific immunoglobulin E if the binding was at least twice the non-specific binding at the total immunoglobulin E concentration of the particular serum. Eleven of the thirty sera of smokers and two of the thirty nonsmokers were positive for pneumococcus-specific immunoglobulin E. By chi-square analysis of these data, the prevalence of pneumococcus-specific immunoglobulin E was significantly greater in the smoking group compared with the non-smoking group (P less than 0.02). These results suggest that the excess immunoglobulin E of smokers is, at least in part, specific for microorganisms that infect the airways.

Adult↗

The specificity of radiostaining in crossed radioimmunoelectrophoresis.

The major allergen from codfish (DS 22) was used to study specific and non-specific radiostaining in crossed radioimmunoelectrophoresis (CRIE). Various modifications of CRIE experiments were performed including experiments where immunoprecipitates in agarose were transferred to test tubes and the radioactivity was measured in a gammacounter. The degree of non-specific binding of IgE and 125 I-anti-IgE to the percipitates was low. A linear relation was found between the amount of human serum IgE antibody used in CRIE and the degree of radiostaining obtained. Increasing the amount of DS 22 in the precipitates from 0.31 to 2.5 microgram resulted in a moderate increase in the uptake of 125 I-anti-IgE, whereas further increase of the amount of DS 22 (5--10 microgram) resulted in reduced uptake of isotope. Serum from a patient containing IgE antibodies to rabbit serum gave rise to radiostaining over the entire antibody-containing gel area, and it is suggested that such human sera be avoided when using CRIE.

Allergens↗

Inheritance of asthma in families and its linkage to HLA haplotypes.

Four families in which asthma occurred in more than three members, and in which there were at least three children, were studied in terms of clinical symptoms, serum IgE levels determined by RIST and RAST, and HLA haplotypes. No association between clinical asthma and serum IgE level was found, but a close association between asthma and a particular HLA haplotype in a family was demonstrated. It was therefore postulated that a disease susceptibility gene closely linked to an HLA gene complex may play a role in the development of asthma.

Asthma↗

Quantitative immunoelectrophoretic analysis of extract from cow hair and dander. Characterization of the antigens and identification of the allergens.

Quantiative immunoelectrophoresis used for the analysis of a dialysed, centrifuged and freeze-dried extract from cow hair and dander revealed 17 antigens. Five of these were identified as serum proteins. Partial identity to antigens of serum and extract from hair and dander of goat, sheep, swine, horse, dog, cat and guinea pig, and to antigens of house dust was demonstrated. Sera from 36 patients with manifest allergy to cow hair and dander selected on the basis of case history, RAST, skin and provocation test, were examined in crossed radioimmunoelectrophoresis (CRIE); sera from five persons with high serum IgE, but without allergy to cow hair and dander, and sera from five normal individuals were controls. 31/36 of the sera contained IgE with specific affinity for two of the antigens of the extract. Further, two major and six minor allergens were identified. The control sera showed no specific IgE binding. A significant positive correlation was found between RAST and CRIE for the first group of patients. The approximate molecular weights of the four major allergens obtained by means of gel chromatography were: 2.4 x 10(4), 2 x 10(4), 2 x 10(5) dalton, respectively. Using Con-A and Con-A Sepharose in crossed immunoaffinoelectrophoresis, eight of the antigens were revealed to contain groups with affinity for Con-A.

Adult↗

Hyposensitization. Comparing a purified (refined) allergen preparation and a crude aqueous extract from timothy pollen.

Most extracts used in hyposensitization (immunotherapy) are complex and ill-defined mixtures of a large number of non-antigenic and antigenic components, only a few of the latter being of significance for allergy and allergen specific immunotherapy. A new purified and well-characterized allergen preparation from timothy pollen is now available, and it has been shown to be superior to the corresponding crude aqueous extract in the diagnosis of IgE-mediated human allergy to timothy pollen. This paper describes the results of hyposensitization for 2 years, with the purified preparation and the crude extract compared. The changes in in vivo and in vitro tests following this treatment in 40 patients with allergic rhinitis due to grass pollen are reported. Both patient groups showed a significant decrease in clinical symptom scores when compared with a control group during the grass pollen season. For all groups the symptom scores correlated well with atmospheric pollen counts. Nasal challenge tests showed a significant increase in nasal tolerance to timothy pollen after 2 years of treatment, but nasal tolerance was unchanged in the control group. Nasal function as a criterion for evaluating the effect of specific hyposensitization is discussed. Serum concentrations of timothy pollen-specific IgE antibodies showed a significant decrease for the group treated with the purified preparation and a slighter and non-significant reduction for the other treated group. There was no significant change in total serum IgE levels. The results indicate that the purified preparation is preferable to the crude aqueous extract in hyposensitization.

Adult↗

Hyposensitization in childhood hay fever. A comparison of refined and whole timothy extracts.

Thirty-six children with well-defined criteria for hay fever (mean age 8 and range 4-15 years) were allocated at random for hyposensitization (HS) with a refined (R) or whole (W) timothy pollen extract during 3-4 years. HS was performed as rush HS with the patients hospitalized for about 1 week and thereafter with monthly injections. Scores for symptoms and antihistamine use were recorded during the season before HS and all seasons during HS. Skin and conjunctival tests were made at the start of HS and postseasonally. Blood samples for IgE and IgG measurements were drawn before and during rush HS and pre- and postseasonally each year. The R-group patients tolerated a higher allergen dose at the end of the rush HS than the W-group ones. They also demonstrated a higher, significant increase in total and specific IgE levels within 7 days and specific IgG levels within 60 days after the start of HS. In both groups postseasonal increases in total and specific IgE levels were seen. The IgG levels increased successively during the treatment. The most remarkable difference between the groups was in scores for symptoms and antihistamine use, which in group R decreased significantly while they increased significantly in group W. Based on these data we recommended that HS, if indicated, should be performed with purified allergen extracts.

Adolescent↗

IgE concentrations measured by PRIST in serum of healthy adults and in patients with respiratory allergy. A diagnostic approach.

In order to establish reference values for total serum IgE in an adult non-atopic population, 175 individuals, 17-85 years of age, were investigated. The usefulness of a sensitive method (PRIST) for serum IgE determinations in discriminating atopy from non-atopic conditions in allergological routine diagnosis was elucidated by investigating 445 patients with symptoms of asthma, rhinitis, urticaria and eczema. Comparisons were made with case histories, in vivo tests and circulating IgE antibodies. The geometric mean for serum IgE in the reference material was 13.2 kU/l with a 2 SD range of 1.53 to 114 kU/l. No significant difference between age groups or sexes was observed. In patients classified as non-atopic and pronounced atopic, the geometric mean values for IgE were 40, 123 and 458 kU/l respectively. The IgE level correlated with number of allergens positive in RAST and with skin test results. It is concluded that IgE determinations are of great help in discriminating atopic conditions from other diseases with similar symptoms. A serum IgE value above 100 kU/l in a patient is strong evidence for the presence of an atopic disease while a value below 20 kU/l indicates that the symptoms are due to intrinsic or infectious disease.

Adolescent↗

Isotopic and enzymatic IgE assays in non-allergic subjects.

In order to establish normal values in an adult population for serum IgE concentration, sera were obtained from 446 ambulatory Canadian caucasian subjects with negative allergy histories. A standard isotopic procedure, the Phadebas paper radioimmunosorbent test (PRIST), was compared with the new enzymatic counterpart, the Phadezyme PRIST. By the isotopic method, serum IgE concentrations in women and men were comparable from one age group to another with no age-related trend in the seven age groups examined (15-20, 21-30, 31-40, 41-50, 51-60, 61-70, above 70). The median and 95th percentile units (U)/ml respectively were 17.5 and 145 for 224 women and 25.5 and 275 for 222 men. Mean values +/- 1 SD for women were 43 +/- 102 and for men, 58 +/- 137. Levels were significantly higher in men as a group. Sera with IgE concentrations above 100 U and a sampling of additional sera were tested for specific IgE antibodies to 13 common allergens by the radioallergosorbent test (RAST). After exclusion of RAST-positive sera, the mean U/ml values +/- 1 SD were 22 +/- 29 for 204 women and 37 +/- 54 for 196 men. Geometric mean U/ml values for these sera were 14.6 for women and 22.3 for men and the median and 95th percentile U/ml respectively for the women were 15 and 66, for the men, 24 and 135. These 95th percentile values are considered the upper limits of normal in this population. The RAST identification of antibodies to allergens to which sensitization was demonstrated provided a potential explanation for serum IgE concentrations above 100 U/ml in less than 30% of the sera in this population with negative allergy histories. The isotopic method and the counterpart enzymatic method (Phadezyme PRIST) were highly comparable; the correlation coefficient (r) for all the sera was +0.93 (P less than 0.001). IgE levels were significantly higher in male smokers than non-smokers by both methods but these differences were not significant in women.

Female↗

Comparative evaluation between two immunoenzymatic techniques (FAST and Phadezym) and the Phadebas RAST in food allergy.

The diagnosis of food IgE-dependent hypersensitivity is based on the demonstration of specific IgE, completed by provocation tests. Two immunoenzymatic techniques, the Phadezym and the FAST, are compared with the Phadebas RAST, in 86 sera (23 controls, 28 from patients with a reported food allergy and 35 with a positive RAST to a food allergen). The within-run variation coefficient of class 0-2 sera was 9% for the Phadebas RAST, and higher than 20% for the Phadezym and the FAST. It was in order of 8.7%, 9.4% and of 17.6% respectively for Phadebas RAST, Phadezym and FAST when estimated with class 3-4 sera. The specificity was higher than 95% for the three techniques. The sensitivity was 75% for Phadebas and 43% for Phadezym and FAST. The FAST test is much less sensitive with allergens of vegetal origin than those of animal origin (P less than 0.01). This work indicates the high percentage of false negative results of immunoenzymatic techniques when food extracts are tested. This could be explained either by an enzyme-substrate reaction or by a non-specific inhibition of the enzyme linked to the anti-IgE IgG.

Adolescent↗

Distribution of serum IgE in children and adolescents aged 7 to 16 years in Copenhagen, in relation to factors of importance.

The distribution of total serum-IgE and factors of importance for the level of IgE was studied in a random sample of 508 children and adolescents, aged 7-16 years, from Copenhagen. A detailed history about asthma, rhinitis, dermatitis and urticaria was obtained, and a physical examination, skin prick test with 9 common allergens, lung function test, bronchial challenge with inhaled histamine and exercise, and measurement of IgE (kU/l) were performed. The distribution of IgE among children and adolescents was found to exhibit a log normal distribution and a positive skin prick test, allergic symptoms, a family history of allergic diseases, age and smoking were found to be significantly related to an increased level of IgE. No relationship was found between increased bronchial responsiveness and IgE. The geometric mean of "normal" values of IgE (*1 SD and *2 SD) of the Danish children and adolescents was 18 kU/l (*4.7, *18.2), suggesting that normal IgE values were within 330 kU/l. Measurement of IgE as the only screening for allergic disease is unreliable, as the predictive value of an elevated IgE in population samples was found to be 50%, whereas misclassification (1-specificity) of asymptomatic subjects as allergic because of an increased IgE was low (4%). In conclusion, total IgE is highly influenced by allergen skin reactivity. Further, this study suggests that normal IgE values were within 330 kU/l, although the range was wide.

Adolescent↗

Serum IgE levels in neurofibromatosis 1.

A descriptive case study was performed on 75 patients with NF1 (neurofibromatosis type 1) from the CNNF (Brazil) database. Serum IgE levels were determined using the IgE radioimmunosorbent test, with the reference values of 75-502 IU mL(-1). The patients were divided into groups, with 25 patients presenting plexiform neurofibromas, 25 presenting neurofibromas and 25 presenting no neurofibromas. The purposes of this study were to determine the serum IgE levels of patients with NF1 presenting plexiform neurofibromas, neurofibromas and no neurofibromas, as well as to determine possible correlations between serum IgE levels and the size of the plexiform neurofibromas and neurofibromas presented by these patients. Elevated serum IgE levels were observed in all the patient groups. We did not observe a correlation between IgE levels and age in these patients; however, we did observe correlations between IgE levels and neurofibroma and plexiform neurofibroma size. We suggest further studies to confirm these results and to investigate in greater depth the possible role of IgE in the development and growth of neurofibromas and plexiform neurofibromas in NF1.

Adolescent↗

Role of specific immunoglobulin E to excretory-secretory antigen in diagnosis and prognosis of hookworm infection.

Total immunoglobulin E (IgE) and specific IgE were assayed by a radioimmunosorbent test and a reverse enzyme immunoassay in patients with hookworm infections before and after treatment. A total of 77 subjects (30 patients with hookworm infections and 47 subjects as controls) were studied. Both specific and total IgE levels in serum and jejunal juice were raised in hookworm patients. There was a significant decrease in IgE levels after therapy. Total IgE levels were raised in other nematode infections, but specific IgE levels were low. The reverse enzyme immunoassay for specific IgE was highly specific (96%) and sensitive (100%) and may be used in the serodiagnosis of hookworm infections.

Adolescent↗

Crossed radioimmunoelectrophoretic studies of distinct allergens in two extracts of Cladosporium herbarum.

Cladosporium herbarum was supplied from two sources and extracted identically. Antisera against the extracts were produced in rabbits and two reference patterns were established using crossed immunoelectrophoresis (CIE). Both patterns showed more than 60 precipitates but less than 50% of the detectable antigens appeared to be identical in the two extracts. The allergens were identified by means of crossed radioimmunoelectrophoresis (CRIE) using sera from 35 individuals with proven or suspected allergy to C. herbarum. Four important and 10-20 less important allergens were demonstrated. Among the allergens present, there were none reacting with all patient sera. Only 1 out of 3 rabbits immunized with a suspension of broken cells of C. herbarum showed precipitating antibodies to the statistically most important allergen, while 9 rabbits immunized with aqueous extracts of the mold did not. The composition of the two extracts with respect to allergens differed. Allergens present in one extract were not always detectable in the other. The experiments also showed how CIE/CRIE with various combinations of antigens and antisera may be combined with CRIE inhibition, radioallergosorbent test (RAST) and RAST inhibition for comparing complex allergen extracts at the molecular level.

Adolescent↗

A reappraisal of IgE levels in various human secretions by particle counting immunoassay combined with pepsin digestion.

We have assayed IgE in various human secretions by particle-counting immunoassay (PACIA). The introduction of a pepsin digestion step of the sample prior to the assay not only eliminates possible interfering factors but also releases from IgE the protease-resistant Fc"epsilon fragment. Since this fragment could represent the residual form of IgE in certain secretions rich in proteases it should be a suitable calibrator for the assay of IgE in secretions. The concentrations of IgE that we found in most fluids (urine, saliva, tears, milk, aqueous humour, cerebrospinal fluid, broncho-alveolar washings, intestinal fluids and faecal extracts) were up to 100 times lower than those reported by others who have used the radioimmunosorbent test (RIST). We suspect that the high values found with RIST are related to the susceptibility of this test to various interfering factors and not to a local production of IgE in most secretions of normal individuals.

Body Fluids↗