Sensitization to cat allergen is associated with asthma in older men and predicts new-onset airway hyperresponsiveness. The Normative Aging Study.

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.

Treatment of cat allergy with T-cell reactive peptides.

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.

Definition of the human T-cell epitopes of Fel d 1, the major allergen of the domestic cat.

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.

Air quality in an animal facility: particulates, ammonia, and volatile organic compounds.

Concentrations of ammonia, volatile organic compounds, particles, and mouse allergen were measured in an animal facility. Ammonia concentrations averaged less than 1 ppm, below any health-based standards. The concentrations of volatile organic compounds were in the 5-15 micrograms/m3 range. Among the volatile organic compounds found, only the terpenes a-pinene and a-terpinol (which may be derived from the pine shavings used as bedding) were consistently present in concentrations greater than outdoor air. The primary air contaminant present at concentrations high enough to be of known physiological significance was the mouse allergen, Mus ml. To determine which activities in an animal room generated the highest concentrations of airborne Mus ml, a monitor that counted particles continuously was used. The particle counts were correlated with allergen levels in the worker's breathing zone (r50.83,p,0.05). Thus, a particle counter can be used effectively in an animal facility to identify specific activities that generate high levels of both particles and allergen. Such activities included changing mice from soiled to clean cages, cleaning floors, and changing foam inserts in pressurized individually ventilated cages. To reduce exposure to allergen during cage changing, which is the major activity for an animal caretaker, a capture-type ventilated changing table was designed and tested. Use of such a table reduced exposure to allergen in the worker's breathing zone from 4.961.1 to 2.160.3 ng Mus ml/m3, a level comparable to background levels.

The effect of relative humidity on mouse allergen levels in an environmentally controlled mouse room.

To determine the effect of humidity on the levels of the mouse allergen Mus m 1, an experimental animal room was constructed to control environmental variables. The sex, strain, age, and number of mice was constant in the room, so that the average daily production of Mus m 1 would not vary greatly. Six different levels of relative humidity from 15% to 65% were maintained for a minimum of a week each. Daily collections of airborne particulates were eluted from filters and Mus m 1 content measured by immunological assay. Increasing relative humidity caused a decrease in Mus m 1 levels from a high of 3 ng/m3 at 15% humidity to a low of 0.5 ng/m3 at 65% humidity. Thus, reduction of airborne allergen levels can be achieved by careful attention to humidity control, especially during the winter heating season when humidity levels may be low. This experimental room can be used to measure the effect of other variables such as ventilation rate, caging, bedding, and work practices on the levels of mouse allergen in an animal facility.

Distribution of airborne mouse allergen in a major mouse breeding facility.

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.

[Specific (allergenic) immunotherapy: bibliographic analysis, efficacy and current practice]. / L'immunothérapie spécifique (allergénique): analyse bibliographique, efficacité et pratiques courantes.

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.

New onset wheezing in an older male population: evidence of allergen sensitization in a longitudinal study. Results of the normative aging study.

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.

Allergen immunotherapy. Review of efficacy and current practice.

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.

Allergy to human seminal fluid: characterization of the allergen and experience with immunotherapy.

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.

Response to intradermal skin testing with four cat allergen preparations in healthy and allergic dogs.

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.

Recommendations for the use of residential air-cleaning devices in the treatment of allergic respiratory diseases.

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.

Cat allergen content of commercial house dust extracts: comparison with dust extracts from cat-containing environment.

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)

Immunologic and biochemical properties of the major mouse urinary allergen (Mus m 1).

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.

A comparative study of the allergens of cat urine, serum, saliva, and pelt.

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.

Immunotherapy in cat-induced asthma. Double-blind trial with evaluation of in vivo and in vitro responses.

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.

Cat allergen 1: Biochemical, antigenic, and allergenic properties.

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.