Search

To explore the relationship between sensitization to inhalant allergens and adult asthma, we performed two nested case-control studies of men being followed in the VA Normative Aging Study. In Study A, 46 subjects (mean age, 61.2 +/- 8.1 yr) with symptoms of asthma and an abnormal methacholine challenge test (cases) were compared with 92 age- and smoking-history-matched subjects, who denied symptoms and had normal methacholine challenge tests (controls). The age of onset of wheezing symptoms for the cases was 49.0 +/- 15.7 yr. Serum IgE reactivity to the aeroallergens Der P 1 and 2, cat, ragweed, and mouse was compared in cases and controls. Cases were more likely to be sensitized to cat allergen (23.9% versus 4.4%, p < 0.001) than were controls. Prevalences of sensitization to Der p 1, Der p 2, ragweed, and mouse were low and similar in the two groups. In Study B, 33 cases who developed new onset airway hyperresponsiveness on methacholine challenge testing were compared with 66 age-matched controls who maintained normal methacholine challenge tests. Cases had a higher prevalence of serum IgE reactivity to cat allergen (18.2% versus 6.1%, p = 0.059) and Der p 2 (21.2% versus 10.6%, p = 0.153) measured in serum obtained 3 yr before the development of airway hyperresponsiveness. These results suggest that in older men, sensitization to cat allergen is associated with asthma and that sensitization predates airway hyperresponsiveness to methacholine.

We induced in allergic humans the counterpart of murine experimental T-cell tolerance. T-cell lines from cat-allergic humans were used to map T-cell epitopes for the principal allergen of cat dander, Fel d 1. Two peptides of 27 amino acids each were synthesized to contain the dominant epitopes (ALLERVAX CAT). After a safety trial, we carried out a blinded study of the dose required for efficacy. We randomly divided 95 cat-sensitive patients into placebo, 7.5 micrograms, 75 micrograms, and 750 micrograms groups. Patients received a subcutaneous injection weekly for 4 wk. Before and after treatment, patients were exposed in a room inhabited by live cats and scored by nose and lung symptoms. Baseline nasal and lung scores (+/-SEM) were 6.2 +/- 0.56 and 5.4 +/- 0.73 in the 750 micrograms group; 7.8 +/- 0.53 and 4.7 +/- 0.68 in the placebo group. Six weeks after treatment, scores adjusted for baseline differences were reduced in the 750 micrograms group: -2.3 +/- 4.9 and -2.3 +/- 0.59 compared with -0.84 +/- 0.50 and -0.85 +/- 0.62 in the placebo group. The 75 micrograms group showed intermediate effects and the 7.5 micrograms group no effect. Linear trend analysis indicated a significant dose response effect: p = 0.05 for nose and 0.03 for lung symptoms. Allergic side effects occurred an hour or more after the first 750 micrograms dose in 16 of 24 patients but required little or no treatment with one exception. T-cell reactive treatment peptides safely improved allergic responses to cats.

Background: A heterodimeric acidic glycoprotein (Fel d 1) has been defined as the major allergen of the domestic cat. Because T-cell help is required for the initiation and maintenance of allergic responses, it is of importance to determine the T-cell-reactive regions of the Fel d 1 molecule., Methods: Overlapping peptides corresponding to the two chains of Fel d 1 were tested in proliferation assays on polyclonal T-cell lines and for the ability to bind Fel d 1-specific IgE in ELISA and histamine release assays., Results: Assay of T-cell lines derived from 53 subjects allergic to cats demonstrated that the majority of T-cell reactivity is found in chain 1 of Fel d 1. Two peptides (Fel-1 and Fel-2) containing major epitopes, alone or as a mixture, efficiently activated T cells and exhibited minimal detectable reactivity with IgE by ELISA or histamine release assay., Conclusions: Two Fel d 1 peptides containing major T-cell epitopes have been identified, have been shown to bind minimal Fel d 1-specific IgE, and are now being tested for the ability to decrease T-cell responses in patients with cat allergy as a new form of immunotherapy.

Background: Occupational allergy to mice is a major cause of disability among workers in mouse breeding and research facilities. Efforts to prevent and treat allergy require a detailed knowledge of exposure levels to allergen., Objective: This study was designed to quantitate the level of major mouse allergen (Mus m I) in central room air and immediate breathing zones under a variety of working conditions., Methods: An Andersen sampler (Groseby Andersen, Spirotech Div., Atlanta, Ga.) was used to collect allergen in each room. A Gillian Personal sampler (Gillian Instrument Corp., West Caldwell, N.J.) collected particles in the worker breathing zone. ELISA was used to quantitate the concentration of Mus m I collected on the two collection devices., Results: Total Mus m I recovered from Andersen samplers ranged from 0.2 to 1.5 ng/m3 in rooms without mice and 0.5 to 15.1 ng/m3 in rooms with mice. Allergen recovered from the zone of worker activity ranged from 1.2 to 2.7 ng/m3 in rooms without mice and from 16.6 to 563.0 ng/m3 in rooms with mice. Direct mouse contact was associated with the highest levels of exposure to Mus m I. Analysis revealed the bulk of allergen to be in mid-particle size ranges (3.3 to 10 microns) for mouse-containing rooms and in small particle size range (0.43 to 3.3 microns) for non-mouse-containing rooms, suggesting that small particles were carried along corridors from rooms with mice into non-mouse-containing rooms. Ventilation characteristics of rooms and mouse population density were evaluated with a "mouse loading" index (number of mice per cubic meter of ventilated air per hour). Mouse loading correlated strongly with small particles (< 3.3 microns) in ambient air., Conclusions: Mus m I is widely distributed within mouse breeding facilities. Direct worker contact with mice seems to be the major factor in high level exposure.

After a history of specific immunotherapy in this exhaustive review, the author discusses the results of all the documented double blind studies and defines rules of good practice for its use in allergic subjects. This takes into account only studies in which the method of evaluation includes an objective index of clinical benefit, such as the drug/symptom or measurement of the threshold of response to provocation. In some cases, the level of improvement seems to be marginal and the variability of responses can be explained by the selection of the subjects and the dose of allergens administered. Only studies done with conventional specific immunotherapy, at high doses, by the injected routes, with extracts that are either aqueous or modified by adsorption or polymerisation have shown results that are clinically significant and these are dose-dependent. Indications for hyposensitisation are discussed fully as well as rules of administration.

Background: Thirty-nine male subjects, with new-onset wheezing, were selected from participants in the Department of Veterans Affairs Normative Aging Study and compared with 74 age-matched controls. Wheezing was defined by responses to a standardized and regularly administered questionnaire. The subjects with wheezing had a reduced FEV1 compared with controls (p = 0.005), but most had values above 80% predicted. Current smoking was more common in subjects with wheezing (36.8% vs 8.11% in controls, p < 0.001). The mean age of both subjects and controls was 64 years., Methods: Allergen-specific IgE antibodies were measured, starting with sera at the time of the most recent questionnaire, and on the average 3.1, 7.6, and 12.3 years before that, with use of stored serum samples., Results: Total IgE did not differ significantly between the groups. IgE binding to dust mite antigen was detected in 13% to 15% of the subjects with wheezing compared with fewer than 7% of the controls over four time intervals (p = 0.014). IgE binding to cat and ragweed antigens did not differ significantly between groups. If current nonsmokers were analyzed separately, IgE binding to cat allergen was also slightly greater in subjects with wheezing compared with controls (p = 0.054). Sequential analysis of IgE antibody levels to mite antigen, over time, indicated that IgE antibody antedated the onset of wheezing., Conclusions: New-onset wheezing in an older adult male population is significantly associated with allergic sensitization to dust mite. There was a borderline association with sensitization to cat in noncurrent smokers only. This supports the hypothesis that a subgroup may have allergic triggers to their symptoms.

The modern use of allergen immunotherapy is described. Evidence for efficacy in inhalant allergy and insect sting allergy is reviewed. Current indications for allergen immunotherapy are discussed.

A 20-year-old woman was observed with a history of a severe generalized systemic reaction after topical contact with seminal fluid. A prick test with undiluted seminal fluid produced a 5.0 mm wheal-and-flare response with pseudopods. Prick tests with saliva and serum from the same source as the seminal fluid were negative. Measurement of IgE antibody to seminal-fluid allergen with a Biotin-Avidin ELISA technique yielded strong activity. No IgG antibody could be detected. Significant prick test reactivity could be found in Sephadex G-100 fractions that had a molecular weight range of 12,000 to 75,000 daltons and that contained approximately 5% of the total protein in the starting material. Isoelectric focusing fractions with strong skin test reactivity had a pI range of 5.4 to 6.6. These fractions contained one major protein band. Immunotherapy was conducted with a Sephadex fraction of seminal fluid during a 24-month period. A cumulative dose of 32 mg of protein was administered. No side effects other than local swelling occurred. Ten months after the start of immunotherapy, IgE antibody became unmeasureable, an effect that was demonstrated not due to the inhibitory effect of IgG antibody. IgG antibody rose progressively in this period. Clinically, the patient became less sensitive to topical contact. Although the natural history of seminal-fluid allergy is not known, immunotherapy may be effective.

Eight commercial cat dander extracts and two pelt extracts derived from mongrel and Siamese cats were compared. Cat allergn 1 and cat albumin were measured by radial immunodiffusion. Allergenic activity was evaluated by prick test and a modified radioallergosorbent test. In the latter, the dilution of each extract that produced 50% inhibition of binding of IgE antibodies to insolubilized cat allergen 1 (RAST 1) and insolubilized cat serum (RAST 2) was determind. The total non-dialysable solid content of the extracts did not correlate with any other parameter. Cat allergen 1 content determined by radial immunodiffusion correlated with average prick test results in ten cat-sensitive subjects and with RAST 1 activity. Cat albumin content correlated weakly with RAST 2 activity but not with any other measure of allergenic activity. Absorption of each extract with the gamma-globulin fraction of rabbit antiserum to cat allergen 1 significantly reduced prick test reactivity and RAST 1 activity, but not RAST 2 activity. These results indicate that cat allergen 1 is an important allergen in cat dander extracts and its measurement may be used to standardize the allergenic activity of such extracts.

Rabbit antiserum to the mouse major urinary protein identified a single antigen that was also found in mouse serum and pelt extract. The skin test reactivity of mouse-pelt extract and mouse urine in two mouse-allergic subjects was significantly reduced after immunoabsorption with the gamma globulin fraction of this antiserum. The antigen defined by this antiserum was designated mouse allergen 1 (MA1). An immunoelectrophoretic procedure was set up to measure its concentration. MA1 had a molecular weight of approximately 19,000 on Sephadex gel filtration and 18,000 to 21,000 on sodium dodecyl sulfate polyacrylamide gel electrophoresis. Isoelectric focusing identified at least four bands with antigenic activity; the major band had an isoelectric point of 3.9. Significant antigenic and allergenic activity of MA1 was retained on reduction and digestion with papain and pepsin. Heating at 90 degrees C for periods up to 180 minutes resulted in a progressive loss, but not abolition, of activity. Serum and urine derived from male mice contained approximately fourfold more MA1 than samples derived from female mice. Urine contained at least 100-fold more MA1 than serum. Of the tissue extracts studied, liver extract had the highest amount of MA1. The immunochemical properties of MA1, its tissue distribution, and sex differences in its concentration provide strong evidence that MA1 is identical to the previously described mouse major urinary protein.

The efficacy of immunotherapy in cat-induced asthma was studied by use of a purified fraction of cat-pelt extract and a double-blind protocol. Nine active-treatment subjects who received a mean cumulative dose of cat allergen, 1 of 10.9 units, and eight placebo-treatment subjects completed the study. Active treatment resulted in significant reductions in bronchial sensitivity (p less than 0.05) and prick test titer (p less than 0.01). In addition, active treatment resulted in a significant delay in the onset of ocular (p less than 0.05) and pulmonary (p less than 0.02) symptoms on exposure to living cats. Significant increases in IgG antibody to cat allergen 1 (p less than 0.001) and cat albumin (p less than 0.01) also occurred with active treatment. There was no significant change in bronchial reactivity to methacholine or in the sensitivity of circulating basophils. These results confirm the validity of immunotherapy in allergic asthma where there is careful patient selection and well defined treatment preparations.

Persistence of outmoded concepts or "myths" concerning the diagnosis and treatment of asthma probably is responsible for large economic losses, overutilization of hospital beds, and many preventable deaths. There have been many worthwhile studies refuting these myths, leading to the following conclusions: Asthma consists of much more than wheezing and in many cases must be treated long after wheezing stops. There is no convincing evidence relating the chronic pulmonary changes of asthma to the psyche. Modern methods of prescribing theophylline have not made it universally effective and safe. Intermittent postive-pressure breathing is rarely justified in asthma. Respiratory acidosis may be corrected only by improving alveolar ventilation. Corticosteroids are usually essential for control of severe asthma and may be used safely. Severe asthmatics need careful monitoring because sudden respiratory failure may occur.

The distribution of the major allergen of the domestic cat, cat allergen 1, was studied in 22 different tissues obtained from a male and female cat and in samples of saliva and urine. Of the cat tissues studied, only extracts of pelt and female brain contained amounts of cat allergen 1 in excess of 0.50 U/ml. Smaller amounts of cat allergen 1 were found in extracts of eye, thyroid, ovary, sublingual gland and large intestine. Unstimulated cat saliva contained a mean of 1.08 U/ml cat allergen 1. Saliva stimulated with ketamine HCl alone, or with ketamine HCl plus pilocarpine, contained 0.68-8.16 U/ml cat allergen 1. In all of the stimulated saliva collections, the total quantity of cat allergen 1 obtained was relatively constant (between 40 and 80 U). These results suggested that the elaboration of cat allergen 1 in saliva is independent of parasympathetic control. Cat allergen 1 could only be detected in cat urine that had been concentrated 9-fold in concentrations of less than 0.5 U/ml. The above results support the hypothesis that the major source of cat allergen 1 is the saliva, and that the presence of cat allergen 1 in the pelt is due to deposition of the allergen during grooming.

In direct RAST analyses of sera from 43 individuals with a history of cat allergy, 39.5% were positive to cat pelt, 37.5% to cat saliva, and 12% each to cat urine and serum. The cat pelt and saliva extracts contained allergen 1, but cat serum and cat urine collected by bladder puncture had no detectable levels of this allergen. A crossed immunoelectrophoresis/crossed radioimmunoelectrophoresis analysis failed to reveal any allergen in urine or serum that was not also present in the saliva or pelt preparations, although urine had two allergens not present in serum. When serum from a patient who was direct RAST positive to cat pelt, serum, saliva, and urine was tested by crossed radioimmunoelectrophoresis, it was determined that a total of six allergens were detectable in cat pelt, three in cat urine, and six in cat serum. Since cat serum contains no detectable cat allergen 1, it may be concluded that at least seven allergens derived from the cat are capable of binding to IgE antibody in humans.

IgE antibodies present in serum from 3 patients clinically sensitive to cat and dog were shown to combine with whole cat and dog sera linked to cellulose particles. Employing a modified radioallergosorbent technique (RAST), it was shown that cat and dog sera inhibited the binding of IgE antibodies to insolubilized cat serum and to insolubilized dog serum. These findings suggest that cat and dog sera have common allergens. Other mammalian sera were also tested and found to have little inhibitory activity. Cat and dog sera did not inhibit the binding of IgE antiragweed antibodies to an insolubilized ragweed fraction. Following separation of cat serum by gel filtration on Sephadex G-200 or electrophoresis in acrylamide gel, several fractions were found to inhibit the binding of IgE antibodies to insolubilized cat and dog sera. Whether the heterogeneity observed reflects the presence of single allergens with diverse size and charge properties or multiple allergens remains to be determined.

In an attempt to recommend standards for room air-cleaning devices, a committee reviewed (1) the types and performance characteristics of available domestic air-cleaning devices, (2) the available data on concentrations of allergens in the indoor air, and (3) the studies that have examined the health effects of the use of indoor air-cleaning devices. Absense of adequate data on the clinical relevance of indoor ambient allergen levels, as well as the effect of air-cleaning devices on these levels, plus a general lack of health effects by these devices in published double-blind studies precluded any firm recommendations for their use. It was clear, however, that use of room air-cleaning devices in the absence of other forms of environmental control was not reasonable.

IgG antibody responses to a major allergen, cat allergen 1 (cat 1), and to a minimally allergenic protein, cat albumin (alb), were studied in patients who had received 4 to 11 mo of immunotherapy with three concentrations of crude cat pelt extract. A double-antibody radioimmunoassay utilizing 125I-labeled antigen was used to measure IgG and IgE antibody. The high-dose group (HDG)(n = 5), which was composed of the active-treatment group of a previously reported double-blind study, received a mean cumulative dose of 3440 microgram cat 1 and 10,660 microgram alb. The intermediate-dose group (IDG) (n = 6) and low -dose group (IDG)(n = 5) received 70 and 0.930 microgram of cat 1 and 217 and 2.86 microgram of alb. IgE antibody to cat 1 before treatment was measurable in most patients. IgE antibody to alb was either no measurable or of a low level. Mean (geometric) before-and-after IgG levels (U/ml) to cat 1 in the HDG, IDG, and LDG were 420 and 7794, 158 and 1388, an 191 and 1365, respectively. Mean before-and-after IgG levels (U/ml) to alb in the HDG, IDG, and LDG were 72 and 348, 1.9 and 4584, and 0.4 and 508, respectively. Two patients (HDG) had no IgG antibody to alb after treatment. Another patient (HDG) had 82,364 U/ml IgG antibody to alb and precipitating antibody by gel diffusion. Very intense IgG antibody response to both cat 1 and alb were seen over a wide range of immunizing doses.

Ten asymptomatic patients with normal pulmonary function were selected for a double-blind trial of immunotherapy in cat-induced asthma. Each patient had a positive prick test to cat pelt extract and also a positive bronchial challenge response to the same extract. Patients were randomly assigned to active treatment or placebo groups and received weekly or biweekly injections over a 3 to 4-month period. The 5 patients who received the active treatment received a cumulative dose of cat pelt extract that ranged from 16.4 to 44.8 mg of total solid containing 1.7 to 4.7 mg of cat allergen 1. Apparent systemic reactions were observed in 3 patients who received the placebo and 3 patients who received the active treatment. The 5 patients who received the active treatment showed a reduction in skin reactivity to cat pelt extract as well as a significant mean reduction in bronchial sensitivity to the same extract. The 5 patients who received the placebo showed no significant changes in skin reactivity or bronchial sensitivity to cat pelt extract. Bronchial response to histamine did not change significantly in either the active treatment of the placebo group.

Eighteen lots of house dust extract from nine commercial sources (obtained as weight per volume or protein nitrogen unit per cubic centimeter) were analyzed for cat allergen content by direct quantitative immunoelectrophoresis after concentration. Cat allergen 1 was measurable (greater than 0.3 units) in 11 extracts with a mean (range) of 5.8 (1.3 to 31.0) U/gm of source material. Cat albumin was measurable (greater than 2.4 units) in 12 extracts with a mean (range) of 53.4 (11.5 to 319.7) U/gm. In order to evaluate whether the cat allergen 1 content is a significant contribution to the allergenic activity of the extract, 17 cat-allergic subjects were tested by prick test with a purified preparation of cat allergen 1. The mean (range) concentration that produced a 3 mm wheal was 0.01 (0.0013 to 1.33) U/ml. Therefore, the commercial house dust extracts studied, when these extracts were diluted to a concentration commonly used for prick testing, would frequently contain enough cat allergen 1 to produce strong prick test reactions in cat-allergic subjects. It is difficult to justify the use of such commercial dust extracts as diagnostic reagents. For comparison purposes, nine dust samples from an apartment housing two cats were similarly analyzed. Cat allergen 1 was measurable in seven samples with a mean (range) of 23.8 (1.8 to 64.3) U/gm. Cat albumin could be measured in all nine samples with a mean (range) of 32.3 (0.16 to 70.8) U/gm. The average amount of cat allergen 1 that could be washed off the surface of the cats was 270 units. Large reservoirs of cat allergen 1 were present.(ABSTRACT TRUNCATED AT 250 WORDS)

Intradermal skin testing with 4 cat allergens was performed on 40 dogs. The allergens used were a commercial preparation, cat allergen 1, cat pelt extract, and cat serum. Twenty dogs had inhalant allergies (canine atopy) and 20 dogs were healthy. The dogs in these 2 groups were further allotted to groups of dogs with or without exposure to cats. Cat pelt extract was the only allergen that caused a statistically significant (P less than 0.025) difference in the number of positive reactions in healthy vs allergic dogs, with healthy dogs having the greater number of positive reactions. Seven (35%) of the 20 dogs with no known exposure to cats had positive reactions to at least one of the allergens. In dogs that had been exposed to cats, positive reactions developed in twice the number of dogs without clinical signs of canine atopy, compared with those with clinical signs of canine atopy. These data showed that dogs do become sensitized to cat allergen, but that this sensitization may not indicate known exposure to cats or clinical disease.

Cat allergen 1, an important agent in human allergic reactions, has been partially purified by affinity chromatography. Heating the purified allergen at 100 degrees C for 30 min resulted in a 28% loss in the antigenicity of the allergen molecule (determined by Laurell rocket assay), although lower temperatures had little effect. Its allergenicity (determined by passive transfer skin test) was diminished slightly after heating to 56 degrees C or 100 degrees C. Reduction with dithiothreitol or 2-mercaptoethanol resulted in greater losses of antigenicity and allergenicity but did not obliterate these properties. Three forms of the affinity-purified allergen (isoallergens) differing slightly in isoelectric point were demonstrated by isoelectric focusing followed by crossed immunoelectrophoresis. The molecular weight of cat allergen 1 under physiologic conditions was 35,000 +/- 2000 as determined by gel filtration in Sephadex G-75. Under the dissociative conditions of sodium dodecyl sulfate-polyacrylamide gel electrophoresis, with or without prior reduction by dithiothreitol, cat allergen 1 appeared to exist as an antigenically active subunit with a molecular weight of 18,000 +/- 2000. This subunit molecular weight estimate was confirmed by gel filtration in 6M guanidine hydrochloride. The stability of the allergenic and antigenic activity of cat allergen 1 suggests that this activity may be determined partially by the primary sequence of allergenic sites on the molecule. The separation and purification of molecular subunits may allow sequence analysis of these sites.

Aqueous extracts prepared from lyophilized, defatted rat, mouse, guinea pig, and rabbit pelts elicited intense wheal-and-flare responses in the skin of a high proportion of patients who were clinically sensitive to these animals. The major allergens in each extract were nondialyzable. Skin test reactions to rat, mouse, and guinea pig serum were common in patients allergic to these animals. The fractions of rat, mouse, and rabbit pelt extract showing maximum allergenic activity contained proteins with the electrophoretic mobility of serum albumin. Fractions of guinea pig pelt extract with maximum allergenic activity were of prealbumin mobility and contained little stainable protein. On Sephadex G-100 gel filtration, most allergen from rat, mouse, and guinea pig pelt extracts was recovered in fractions containing proteins with a molecular weight range of 10,000 to 25,000 daltons. Allergen in rabbit pelt extract had a slightly higher molecular weight range of 18,000 to 38,000 daltons.

Extrinsic asthma is caused by exposure to airborne allergens. The diameter of airborne particles influences the depth of penetration and deposition fraction in the lung. In this study, we used an Andersen sampler to collect 9 different size ranges of airborne particles from a cat-containing and a cat-free room. We detected cat allergen 1 (CA1), the major cat allergen, using a rocket immunoelectrophoretic technique in larger particle size ranges (more than 5 mu). Using in vitro cat allergic donor basophil histamine release, cat-associated allergen activity was detected in particle size ranges from 10 to less than 1 mu in aerodynamic diameter. Control collections of airborne particles from a cat-free room showed little or no allergen activity, and nonatopic donor basophils did not release histamine in response to any of these samples. The P-K test (positive transfer test) confirmed findings of the other assays. We conclude that cat-derived allergens are associated with a large range of airborne particle sizes that penetrate into the peripheral lung.