1. Compliance with an allergen immunotherapy regime.

Tinkelman D, Smith F, Cole WQ 3rd, Silk HJ. Atlanta Allergy Clinic, GA 30328.

BACKGROUND: Compliance with an allergy immunotherapy regimen is obviously the difference between a potentially successful or unsuccessful outcome. OBJECTIVE: The purpose of this study was to assess retrospectively compliance of patients receiving immunotherapy in a private allergy practice. METHODS: The study evaluated retrospectively patient compliance with prescribed allergy injections for a private practice in Atlanta, Georgia. Patients who ordered allergy extract material for their injection immunotherapy program during an 18-month period served as the index population for this study. For the purposes of this study, noncompliance was defined as stopping the allergy injection program without the approval of the prescribing physician. Part of this investigation was to determine whether there were compliance differences between those who received their allergy injections within the confines of the clinic and those who received their injections at outside physician offices. A 12-month period of review was considered adequate to monitor compliance because of the 12-month expiration date placed on the allergy extracts. RESULTS: There was a noncompliance rate of 10: 77% for those who received their injections within the clinic. This contrasted with the noncompliance rate in the remote population of 34.82%. The difference between these two groups was statistically significant (P < .01). There were no statistical differences with respect to sex or diagnostic category. Significant differences were found between age groups in those receiving injections within or outside the clinic. CONCLUSIONS: There is a much higher rate of noncompliance in those who receive their injections in facilities outside the allergist's office. This suggests that to ensure better compliance either individuals should either be encouraged to receive their injections at the allergist's office, or better communications should be established between the referring allergist and the nonallergy physicians who are administering the injections.

Source: Ann Allergy Asthma Immunol 1995 Mar;74(3):241-6

KEYWORD(S): Adolescence; Adult; Age Factors; Aged; Child, Preschool; *Desensitization, Immunologic; Female; Georgia; Home Infusion Therapy; Human; Infant, Newborn; Middle Age; *Patient Compliance; Retrospective Studies; Sex Factors; UI=95196060

2. Successful replacement of allergen-specific immunotherapy by

allergen-mixture therapy.

Title Abreviation: Ann Allergy Asthma

Immunol Date of Pub: 1995 Nov

Author: Song CH; Heiner DC;

Issue/Part/Supplement: 5 Volume Issue: Pagination: 402-8

75

MESH Headings: Adult; Aged; Allergens (*IM); Comparative Study; Female;

Human; Hypersensitivity (*TH); Immunotherapy (*MT); Male; Middle Age; Skin

Tests; -RN-;

Journal Title Code: CBM Publication Type: JOURNAL ARTICLE

Date of Entry: 951226N Entry Month: 9602

Country: UNITED STATES Index Priority: 1

Language: Eng Unique Identifier: 96075510

Unique Identifier:

96075510 ISSN: 1081-1206

Abstract: BACKGROUND: Some clinicians utilize allergen-specific immunotherapy (specific therapy), employing only the extracts of allergens that produce positive skin tests. Others use allergen-mixture immunotherapy (mixture therapy), employing premixed extracts containing both skin reactive and non-reactive (irrelevant) allergens. OBJECTIVE: The purpose of this study was to compare the efficacy of these two approaches and to identify sensitization to irrelevant allergens included in mixture therapy. METHOD: A total of 20 adults with allergic rhinitis/asthma who were switched from successful specific therapy (average duration of 6.1 years) to mixture therapy (2.0 years) were evaluated with symptom-medication scores, skin test results, and local/systemic reactions at three time points: before specific therapy, before, and 2 years after mixture therapy. RESULTS: Symptom-medication scores for all patients improved at the end of specific therapy and remained improved during mixture therapy (12.3 versus 12.0 with P = .75). The sums of positive skin tests at three points were not different (7.8 versus 8.3 versus 9.8 with P > .4 at all points). Reaction rates did not differ either. Skin sensitization to irrelevant allergens occurred in five patients during mixture therapy. These patients, however, also experienced spontaneous conversions from negative to positive reactions to the allergens not included in the therapy, indicating that sensitization may be partly due to a spontaneous increase in skin reactivity. CONCLUSION: These findings suggest that allergen-mixture immunotherapy is as efficacious as allergen-specific therapy and may be associated with skin sensitization in some patients. There was no evidence of increased adverse clinical reaction.

Abstract By: Author

Address: Department of Pediatrics, Harbor-UCLA Medical Center, Torrance,

USA.

3. Introduction: risk management in asthma and allergic diseases.

Author

Du_Buske_LM

Address

Immunology Research Institute of New England, Fitchburg, MA 01420, USA.

Source

J Allergy Clin Immunol, 1996 Dec, 98:6 Pt 3, S289-90

Abstract

The recent advances in therapy for allergic diseases, including

allergic rhinitis, asthma, and urticaria, have posed new challenges to

physicians who must carefully assess the risks and benefits to the

patient of new treatment. Appreciation of the drug interaction between

certain second-generation antihistamines, including terfenadine and

astemizole, with selective macrolide antibiotics and imidazole

antifungal agents leading to QTc interval prolongation, and the

potential for fatal cardiac arrhythmias is an example of the need to

assess risks of therapy. Risk management in allergic disease includes

minimizing disease morbidity by emphasizing allergen avoidance in

asthma and by minimizing the therapeutic morbidity and mortality that

can occur when allergen immunotherapy is administered either

improperly, such as in an unsupervised setting, or inappropriately,

such as to unstable asthmatics. Physicians must carefully weigh the

benefits of therapies designed to decrease costs, including regimens

combining second- and first-generation antihistamines, considering both

the potential risk ensued related to sedation and impaired cognitive

performance when using first-generation antihistamines and the unproven

efficacy of such regimens. Clearly, risk management in asthma and

allergic disease will become more complex with greater understanding of

mechanisms of allergic disease, of provocative factors exacerbating

allergic disease, of the potential adverse consequences of therapy, and

of the potential interaction among therapeutic modalities. It is

essential that physicians treating the nearly 20% of Americans who have

allergic disease thoroughly appreciate the risks and benefits of their

therapeutic decisions.

Language of Publication

English

Unique Identifier

97132082

4. Risk management in allergen immunotherapy.

Author

Greineder_DK

Address

Harvard Community Health Plan Kenmore Center, Allergy Department,

Boston, MA 02215, USA.

Source

J Allergy Clin Immunol, 1996 Dec, 98:6 Pt 3, S330-4

Abstract

The major risk of allergen immunotherapy is the development of systemic

anaphylactic reactions. The reported frequency of systemic reactions

after allergen immunotherapy varies from < 1% in patients receiving

conventional immunotherapy to > 36% in patients receiving rush

immunotherapy. Fatal and systemic reactions to allergen immunotherapy

have similar characteristics. The onset of both types of reaction

occurs < 30 minutes after injection in approximately 70% of patients.

The most common risk factors for fatal and systemic reactions to

allergen immunotherapy include a history of asthma, increasing allergen

dose, high allergen sensitivity, previous systemic reaction, and

injection during an active allergen season. On the basis of findings

from several studies, precautions during allergen immunotherapy have

been recommended. In addition, several interventions, including

premedication with antihistamines or corticosteroids, measurement of

peak flow before injection, and access to an antihistamine or

injectable epinephrine after an allergen injection, have been suggested

as measures to prevent reactions to and improve the safety of allergen

immunotherapy. However, additional studies are necessary before these

regimens are implemented routinely in allergen immunotherapy protocols.

Language of Publication

English

Unique Identifier

97132088

5. The role of immunotherapy in pediatric allergic disease.

Title Abreviation: Curr Opin Pediatr Date of Pub: 1995 Dec

Author: Hedlin G;

Issue/Part/Supplement: 6 Volume Issue: Pagination: 676-82

7

MESH Headings: Child; Human; Hypersensitivity (*TH); Immunotherapy (*/MT);

Rhinitis (TH); -AA-;

Journal Title Code: BUT Publication Type: JOURNAL ARTICLE

Date of Entry: 961202N Entry Month: 9702

Country: UNITED STATES Index Priority: 2

Language: Eng Unique Identifier: 96372195

Unique Identifier: 96372195 ISSN: 1040-8703

Abstract: Knowledge of the mechanisms of immunotherapy has increased

substantially in recent years. The development of better extracts for both

injection immunotherapy and local immunotherapy continues, and techniques

for the production of recombinant allergens and peptides will be important

for future vaccines. Immunotherapy with conventional commercially

available extracts is best documented in childhood pollen allergy and is

useful in children with severe hay fever symptoms or seasonal asthma.

Immunotherapy for perennial allergy has so far been most beneficial in

dust mite- and cat-allergic children with asthma. Dust mite therapy is

most efficacious in children with isolated dust mite allergy. Appropriate

environmental measures should, however, precede immunotherapy when

possible. Recent data indicate that immunotherapy has no additional

benefit in children with multiple allergies and asthma who receive optimal

pharmacotherapy. It is therefore preferable that immunotherapy be combined

with anti-inflammatory drug therapy in most children with asthma. For

safety reasons, it is important that immunotherapy be administered by

physicians well acquainted with standardized extracts in a clinic or

hospital where treatment for systemic reactions is available. Long-term

treatment for 3 to 5 years results in a more sustained effect than

short-term therapy.

Abstract By: Author

Address: Huddinge University Hospital, Stockholm, Sweden.

Number of References: 43

6. Pain and dermal reaction caused by injected glycerin in immunotherapy

solutions.

Author

Van_Metre_TE_Jr; Rosenberg_GL; Vaswani_SK; Ziegler_SR; Adkinson_NF

Address

Johns Hopkins University School of Medicine, Department of Medicine,

Baltimore, MD, USA.

Source

J Allergy Clin Immunol, 1996 May, 97:5, 1033-9

Abstract

BACKGROUND: Fifty percent glycerin preserves immunotherapy solution

potency for at least 3 years but must be diluted before injection to

reduce glycerin-induced pain and inflammation. We studied pain,

erythema, induration, and bruises caused by glycerin (0% to 30%).

METHODS: In 15 healthy subjects we compared, in double-blind fashion,

pain scores, injection site erythema, induration, and bruising caused

by subcutaneous injections in randomized order of 0.1, 0.5, and 1 ml of

glycerin 0%, 10%, 20%, and 30%. RESULTS: Injection volume did not

significantly influence pain scores from diluent alone (0% glycerin) (p

greater than 0.1). Pain scores of subjects given glycerin (0.1 to 1 ml,

10% to 30%) increased significantly as both injection volume (p less

than 0.001) and glycerin concentration (p less than 0.001) increased.

Pain scores correlated with total glycerin dose administered (volume x

concentration) (rs = 0.67, p less than 0.0005) but varied widely, from

minimal to severe, in those given the same dose. Injection site

erythema, induration, and bruising occurred in some subjects with

significant positive correlations between total glycerin dose and both

frequency and diameters of erythema and induration. However, these

dermal reactions were of trivial clinical importance. CONCLUSION:

Injected glycerin produces pain that is proportional to total injected

dose of glycerin, but individual variation in perceived discomfort is

substantial. Total glycerin doses of less than 0.05 ml rarely produce

clinically important pain.

Language of Publication

English

Unique Identifier

96212659

7. Antihistamine premedication in specific cluster immunotherapy: a

double-blind, placebo-controlled study.

Author

Nielsen_L; Johnsen_CR; Mosbech_H; Poulsen_LK; Malling_HJ

Address

Medical Department, National University Hospital, Copenhagen, Denmark.

Source

J Allergy Clin Immunol, 1996 Jun, 97:6, 1207-13

Abstract

BACKGROUND: Specific immunotherapy treatment in allergic diseases

involves a risk of systemic side effects. A double-blind,

placebo-controlled study was performed in 45 patients allergic to

pollen to determine whether pretreatment with loratadine could reduce

the number and severity of systemic reactions during the dose-increase

phase of cluster immunotherapy. METHODS: The patients received cluster

immunotherapy with a standardized birch (Betula verrucosa) or grass

(Phleum pratense) pollen extract adsorbed to aluminum hydroxide. The

immunotherapy schedule involved seven visits and 14 injections to reach

a maintenance dose of 100,000 standardized quality units. Loratadine,

10 mg, or placebo tablets were administered 2 hours before the first

injection at each visit. RESULTS: A total of 720 injections were given

(309 injections in 21 patients receiving loratadine and 411 injections

in 24 patients receiving placebo). The median numbers of injections to

reach maintenance dose were 15 (range, 14 to 18) in the loratadine

group and 16 (range, 14 to 23) in the placebo group (p = 0.037). The

numbers of patients with systemic reactions were seven (33%) and 19

(79%) in the loratadine and placebo groups, respectively (p = 0.002).

Twenty-five reductions caused by systemic reactions were observed in

the placebo group in contrast to nine in the loratadine group (p =

0.047). No life-threatening systemic reactions were observed in either

group. Systemic reactions were, however, more severe in the placebo

group, mainly because of a significantly higher incidence of urticaria

(10 vs 1, p = 0.022). CONCLUSION: Pretreatment with loratadine seems to

reduce both the number and severity of systemic reactions in specific

cluster immunotherapy.

Language of Publication

English

Unique Identifier

96243698

8. Safe allergen immunotherapy. The correct allergen, the appropriate

patient, the adequate dose.

Title Abreviation: Postgrad Med Date of Pub: 1996 Aug

Author: Schoenwetter WF;

Issue/Part/Supplement: 2 Volume Pagination: 123-6, 131-5

Issue: 100

MESH Headings: Desensitization, Immunologic*; Human; Hypersensitivity*;

Time Factors*; -PG-;

Journal Title Code: PFK Publication Type: JOURNAL ARTICLE

Date of Entry: 960904N Entry Month: 9611

Country: UNITED STATES Index Priority: 1

Language: Eng Unique Identifier: 96323047

Unique Identifier: 96323047 ISSN: 0032-5481

Abstract: Effective immunotherapy has been shown to be allergen-specific,

dose-dependent, and duration-dependent. Patients must receive adequate

doses of the relevant allergen to obtain benefit, and most require 3 to 5

years of injections to maintain prolonged benefit after injections are

stopped. Concurrently, patients must cooperate by modifying their

environment and using some medications during difficult seasons. Although

serious reactions to immunotherapy are relatively rare, a physician must

be readily available whenever injections are administered, and office

staff need to recognize and be ready to respond to systemic reactions.

Abstract By: Author

Address: Asthma and Allergy Research Center, Park Nicollet Clinic,

Minneapolis, USA.

Number of References: 17

1. Oral allergy syndrome successfully treated with pollen

immunotherapy.

Title Abreviation: Ann Allergy Asthma

Immunol Date of Pub: 1995 May

Author: Kelso JM; Jones RT; Tellez R; Yunginger JW;

Issue/Part/Supplement: 5 Volume Issue: Pagination: 391-6

74

MESH Headings: Adult; Case Report; Desensitization, Immunologic (*);

Electrophoresis, Polyacrylamide Gel; Food Hypersensitivity (ET/*TH); Fruit

(AE); Glossitis (ET/*TH); Hay Fever (ET/TH); Human; IgE (AN); Male; Mouth

Mucosa (PA); Pharyngitis (ET/*TH); Pollen; Skin Tests; Support, Non-U.S.

Gov't; Syndrome; Vegetables (AE); -RN-;

Journal Title Code: CBM Publication Type: JOURNAL ARTICLE

Date of Entry: 950620N Entry Month: 9508

Country: UNITED STATES Index Priority: 1

Language: Eng Unique Identifier: 95269116

Unique Identifier: 95269116 ISSN: 1081-1206

Abstract: BACKGROUND: Some patients with allergic rhinitis have oral

allergic reactions to fresh fruits and vegetables. This phenomenon has

been termed "oral allergy syndrome" and is proposed to be due to

cross-reacting allergens in the foods and pollens. METHODS: We report a

patient with allergic rhinitis and oral allergy syndrome treated with

pollen immunotherapy. Prior to immunotherapy, eating any fresh fruit or

vegetable caused immediate itching and swelling of his tongue and throat.

Prick skin test titration with pollens and foods was performed before and

after 13 months of immunotherapy. Specific IgE immunoassay was performed

with the same extracts on serum obtained before and after 7 and 13 months

of immunotherapy. IgE immunoblots were performed on the same extracts

separated by polyacrylamide gel electrophoresis using sera from the same

time periods. RESULTS: After 1 year on immunotherapy, the patient's

allergic rhinitis symptoms resolved, and he was able to eat fresh fruits

and vegetables without reaction. Skin testing and specific IgE immunoassay

demonstrated a marked reduction in sensitivity to not only the pollens but

the foods as well. Immunoblots revealed that the intensity of IgE binding

to most components of the extracts, some common to pollens and foods,

declined during immunotherapy. CONCLUSIONS: These results support the

notion that oral allergy syndrome is due to cross-reacting allergens in

foods and pollens and may be amenable to treatment with pollen

immunotherapy.

Abstract By: Author

Address: Department of Internal Medicine (Allergy Division, Naval Medical

Center, San Diego, California, USA.

2. Immunotherapy with a standardized Dermatophagoides pteronyssinus

glutaraldehyde-modified extract against an unmodified extract: a

comparative study of efficacy, tolerance and in vivo and in vitro

modification of parameters.

Title Abreviation: J Investig

Allergol Clin Immunol Date of Pub: 1995 Nov-Dec

Author: Echechiplia S; Tabar AI; Lobera T; Mulnoz D; Rodrliguez A; Blasco

A; Olagulibel JM; Casanovas M; Fernlandez de Corres L;

Issue/Part/Supplement: 6 Volume Pagination: 325-32

Issue: 5

MESH Headings: Adolescence*; Adult*; Animal; Asthma*; Bronchial

Provocation Tests*; Child*; Comparative Study; Desensitization,

Immunologic*; Evaluation Studies*; Female; Human; IgE*; IgG*; Male;

Mites*; Rhinitis, Allergic, Perennial*; Skin Tests*; Treatment Outcome*;

-PG-;

Journal Title Code: BYJ Publication Type: CLINICAL TRIAL

Date of Entry: 960801N Entry Month: 9610

Country: SPAIN Index Priority: 2

Language: Eng Unique Identifier: 96246784

Unique Identifier:

96246784 ISSN: 1018-9068

Abstract: We comparatively studied clinical efficacy, tolerance and

modifications of different in vivo and in vitro parameters induced by two

biologically standardized Dermatophagoides pteronyssinus extracts (HEP

units), one glutaraldehyde-modified, in patients with allergic rhinitis

and/or bronchial asthma after a year of treatment. A decrease in drug

consumption was observed in both treatment groups (p < 0.0001). Of all the

in vivo parameters studied (cutaneous, conjunctival and bronchial

reactivity to the allergen), a decrease in specific bronchial reactivity

was only observed in the group treated with the modified extract (p <

0.05). The modifications in total IgE, specific IgE and specific total IgG

levels are superimposable on those described in previous papers on

immunotherapy. However, IgG4 levels remained stable with respect to time.

Tolerance was good and very similar for both treatments; both types of

extracts are equally efficacious and safe.

Abstract By: Author

Address: Allergy Service, Santiago Aplostol Hospital, Vitoria, Spain.

3. Long-term follow-up of patients treated with a three-year course of

cat or dog immunotherapy.

Title Abreviation: J Allergy Clin Immunol Date of Pub: 1995 Dec

Author: Hedlin G; Heilborn H; Lilja G; Norrlind K; Pegelow KO; Schou C;

Lowenstein H;

Issue/Part/Supplement: 6 Pt Volume Issue:

1 96 Pagination: 879-85

MESH Headings: Adult; Animal; Asthma (BL/IM/*TH); Bronchial Provocation

Tests; Cats; Child; Child, Preschool; Desensitization, Immunologic (*);

Dogs; Double-Blind Method; Follow-Up Studies; Human; IgE (BL); IgG (BL);

Questionnaires; -RN-;

Journal Title Code: H53 Publication Type: JOURNAL ARTICLE

Date of Entry: 960213N Entry Month: 9604

Country: UNITED STATES Index Priority: 1

Language: Eng Unique Identifier: 96133466

Unique Identifier: 96133466 ISSN: 0091-6749

Abstract: BACKGROUND: A 5-year follow-up study was conducted to

investigate the duration of the effects of a 3-year course of

immunotherapy with standardized cat or dog extracts in 32 children and

adults with asthma caused by animal dander. METHODS: Thirty of the

subjects could be reached with a questionnaire, 19 underwent bronchial

allergen and histamine challenges, and four had only a histamine

challenge. Specific IgE and IgG4 levels in serum were measured in those

who underwent challenges. RESULTS: Almost all subjects (26 of 30) reported

no change (17 subjects) or increased tolerance (9 subjects) on exposure to

cats or dogs. In contrast, 17 of the 19 who underwent allergen challenges

had increased allergen sensitivity compared with when therapy was stopped

(p < 0.01), and the results were no longer significantly different from

before therapy was started. Mean provocative concentration of histamine

causing a 20% fall in peak expiratory flow was, however, still higher than

before therapy in the cat immunotherapy group (p < 0.01) and had not

changed significantly during the follow-up period. In the dog

immunotherapy group there was no significant change during or after

therapy. Specific IgG4 had decreased, and specific IgE in serum had

remained low and was comparable to the levels measured at the end of the

study period. CONCLUSIONS: Five years after stopping immunotherapy,

objectively measured bronchial allergen sensitivity had increased and had

approached pretreatment conditions. Asthma symptoms, according to

patients' subjective evaluations, had continued to be mild in most

patients, and bronchial histamine sensitivity had remained stable. These

observations could reflect remaining effects of immunotherapy or the

natural history of mild asthma.

Abstract By: Author

Address: Department of Pediatrics B57, Karolinska Institutet, Huddinge

Hospital, Sweden.

4. Ragweed immunotherapy in adult asthma [see comments]

Title Abreviation: N Engl J Med Date of Pub: 1996 Feb 22

Author: Creticos PS; Reed CE; Norman PS; Khoury J; Adkinson NF Jr; Buncher

CR; Busse WW; Bush RK; Gadde J; Li JT; Richerson HB; Rosenthal RR; Solomon

WR; Steinberg P; Yunginger JW;

Issue/Part/Supplement: 8 Volume Issue: Pagination: 501-6

334

MESH Headings: Adult; Asthma (ET/IM/*TH); Bronchial Provocation Tests;

Desensitization, Immunologic (*/AE/EC); Double-Blind Method; Female; Hay

Fever (CO/*TH); Human; Immunoglobulins (BL); Male; Skin Tests; Support,

Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Treatment Outcome; -RN-;

Journal Title Code: NOW Publication Type: CLINICAL TRIAL

Date of Entry: 960223N Entry Month: 9605

Country: UNITED STATES Index Priority: 1

Language: Eng Unique Identifier: 96157014

Unique Identifier:

96157014 ISSN: 0028-4793

Abstract: BACKGROUND. Although allergen immunotherapy is effective for

allergic rhinitis, its role in treating asthma is unclear. METHODS. We

examined the efficacy of immunotherapy for asthma exacerbated by seasonal

ragweed exposure. During an observation phase, adults with asthma who were

sensitive to ragweed kept daily diaries and recorded peak expiratory flow

rates between July and October. Those who reported seasonal asthma

symptoms and medication use as well as decreased peak expiratory flow were

randomly assigned to receive placebo or ragweed-extract immunotherapy in

doses that increased weekly for an additional two years. RESULTS. During

the observation phase, the mean (+/- SE) peak expiratory flow rate

measured in the morning during the three weeks representing the height of

the pollination season was 454 +/- 20 liters per minute in the

immunotherapy group and 444 +/- 16 liters per minute in the placebo group.

Of the 77 patients who began the treatment phase, 64 completed one year of

the study treatment and 53 completed two years. During the two treatment

years, the mean peak expiratory flow rate was higher in the immunotherapy

group (489 +/- 16 liters per minute, vs. 453 +/- 17 in the placebo group

[P = 0.06] during the first year, and 480 +/- 12 liters per minute, vs.

461 +/- 13 in the placebo group [P = 0.03] during the second). Medication

use was higher in the immunotherapy group than in the placebo group during

observation and lower during the first treatment year (P = 0.01) but did

not differ in the two groups during the second year (P = 0.7).

Asthma-symptom scores were similar in the two groups (P = 0.08 in year 1

and P = 0.3 in year 2). The immunotherapy group had reduced hay-fever

symptoms, skin-test sensitivity to ragweed, and sensitivity to bronchial

challenges and increased IgG antibodies to ragweed as compared with the

placebo group; there was no longer a seasonal increase in IgE antibodies

to ragweed allergen in the immunotherapy group after two years of

treatment. Reduced medication costs were counterbalanced by the costs of

immunotherapy. CONCLUSIONS. Although immunotherapy for adults with asthma

exacerbated by seasonal ragweed exposure had positive effects on objective

measures of asthma and allergy, the clinical effects were limited and many

were not sustained for two years.

Abstract By: Author

Address: Department of Medicine, Johns Hopkins University School of

Medicine, Baltimore, MD, USA.

July 18, 1996 -- Volume 335, Number 3

----------------------------------------------------------------------------

[CORRESPONDENCE]

Ragweed Immunotherapy in Adult Asthma

----------------------------------------------------------------------------

To the Editor:

Creticos et al. (Feb. 22 issue) (1) found that in adults with

asthma exacerbated by seasonal exposure to ragweed, immunotherapy

improved objective measures of asthma and allergy, but the

clinical effects were limited, and many were not sustained over a

period of two years. Their findings support the conclusions of our

meta-analysis of randomized, controlled trials. (2) However, their

failure to demonstrate a significant difference from base line in

medication use and asthma symptoms in the second year requires

critical analysis.

 

Screening of volunteers resulted in a drop in the number of

suitable subjects from 1000 to 127. One of the inclusion criteria

was worsening of asthma during the fall season, but what

constituted worsening is not stated. This may have resulted in the

selection of a group biased toward pronounced worsening. There was

a difference in the attrition of subjects randomly assigned to

placebo (16 of 40 patients) and that of subjects assigned to

immunotherapy (8 of 37). This would have reduced the statistical

power of the trial to identify significant differences in the

second year.

 

The medication score lumped bronchodilator and antiinflammatory

drugs together, and therefore, it is not possible to identify

patients who were dependent on corticosteroids. Various doses of

medications were scored as 1 unit, including one puff of a nasal

corticosteroid. Nasal corticosteroids can relieve upper-airway

symptoms and assist indirectly in asthma control, but they should

not be considered antiasthma drugs. For oral corticosteroids 0.5

mg of prednisone was scored as 1 unit. The inclusion of small

numbers of patients with frequent or sustained use of oral

corticosteroids during the analysis period, perhaps because of

viral infection, could have skewed the data. For example, during

week 6 of the second year the higher amount of medication used by

subjects randomly assigned to immunotherapy, as compared with

those assigned to placebo, could be explained by the inclusion of

as few as three patients who required 50 mg of prednisone daily.

The identification of each class of medication would allow a

proper comparison of the groups.

 

Finally, the peak ragweed-pollen count ranged from 600 to 1500

pollen grains per cubic meter, but there was no comparison of the

pollen counts for each treatment year. A less intense pollen

season (fewer days with a high pollen count) in the second year

could have reduced the difference between the treatment and

control groups.

 

John Weiner, F.R.A.C.P.

Michael Abramson, F.R.A.C.P.

Robert Puy, F.R.A.C.P.

John Wilson, F.R.A.C.P.

Monash University Medical School

Melbourne, VIC 3181, Australia

 

References

 

1. Creticos PS, Reed CE, Normal PS, et al. Ragweed immunotherapy

in adult asthma. N Engl J Med 1996;334:501-6.

Return to: Text

 

2. Abramson MJ, Puy RM, Weiner JM. Is allergen immunotherapy

effective in asthma? A meta-analysis of randomized controlled

trials. Am J Respir Crit Care Med 1995;151:969-74.

Return to: Text

------------------------------------------------------------------

To the Editor:

 

The study by Creticos et al. is an important addition to the

medical literature. However, as officials of the American College

of Allergy, Asthma and Immunology, we are disturbed by the

interpretation of the data in the accompanying editorial by

Barnes. (1)

 

Barnes fails to acknowledge the principal finding that

immunotherapy had a beneficial effect on peak expiratory flow

rates and sensitivity to bronchial provocation by allergens

despite decreased medication use in the active-treatment group.

This conclusion is corroborated by the reduced seasonal increase

in IgE and the reduced skin-test sensitivity to ragweed.

 

The difference in symptom scores between the active-treatment and

placebo groups did not reach statistical significance; however,

the patients in the placebo group were taking more medication than

those in the active-treatment group. Instead of concluding that

immunotherapy was not effective, can one not with equal likelihood

conclude that the improvement in the placebo group was due to

greater use of medications? Also, might the apparently reduced

efficacy in the second year represent regression toward the mean,

given the continued efficacy in the third year in some

participants?

 

Patients with asthma who are sensitive only to ragweed are rare;

it was necessary to include patients with sensitivities to other

antigens. Exposure to these antigens may peak during the ragweed

season in much of the United States; hence, it is remarkable that

a significant difference was found for any of the measured

variables.

 

Barnes's comments about the safety of immunotherapy should be

balanced against the alarming increase in mortality rates for

asthma. He concludes that the cost of immunotherapy is difficult

to justify in view of the relatively small gain. However, Creticos

et al. found that pulmonary function increased and medication use

and asthma-symptom scores decreased after a year of immunotherapy.

The difference in the cost of medication was $2.50 more per week

for immunotherapy. Patients whose quality of life improved might

have a different view than Barnes of the balance of costs and

benefits.

 

Barnes states that drug therapy and the avoidance of allergens are

the recommended approach to the management of asthma but does not

reveal whose recommendation this is. In the United Kingdom,

immunotherapy is an infrequent procedure for reasons not

necessarily scientific. The actual findings of the study by

Creticos et al. and of the other numerous studies that have

demonstrated the efficacy of immunotherapy in asthma by objective

measures should be remembered.

 

Jay M. Portnoy, M.D.

Ira Finegold, M.D.

American College of Allergy, Asthma and Immunology

Arlington Heights, IL 60005

 

References

 

1. Barnes PJ. Is immunotherapy for asthma worthwhile? N Engl J Med

1996;334:531-2.

Return to: Text

------------------------------------------------------------------

To the Editor:

 

In the study by Creticos et al., the reported effects of treatment

were not limited as compared with those of most other treatments

for asthma subjected to one-year controlled trials. In his

editorial, Barnes concludes that the "small" effects of

immunotherapy are not worthwhile when compared with those of other

treatments that are "highly effective." He states that "inhaled

glucocorticoids are of particular value." This view appears to

ignore the fact that hospital admissions for asthma in the United

Kingdom and elsewhere have continued to rise despite widespread

use of inhaled glucocorticoids. The editorial supports the case

for inhaled-corticosteroid treatment by citing a Canadian study on

rhinitis that compared topical budesonide with immunotherapy using

modified ragweed tyrosine adsorbate (Pollinex-R). (1) This is a

surprising choice, since this preparation of allergen, which is

first treated with glutaraldehyde and then adsorbed to tyrosine,

has not been shown to be clinically effective and does not produce

an IgG antibody response.

 

In the United Kingdom, physicians and patients are generally not

aware of the high costs of inhaled corticosteroids and there are

very few specialists in the management of allergic disease. Barnes

refers to the use of immunotherapy in "general practice." It was

precisely physicians in general practice in the United Kingdom who

encountered severe side effects when administering immunotherapy.

In the United States immunotherapy is carried out by specialists

and is reserved for patients who have not responded adequately to

treatment with inhaled medicines and avoidance of specific

allergens.

 

It is clear from a recent meta-analysis (2) and the report by

Creticos et al. that immunotherapy can be an effective treatment

for asthma and should be considered in cases of mild-to-moderate

asthma in which other treatments do not produce adequate control.

 

Thomas A.E. Platts-Mills, M.D., Ph.D.

University of Virginia

Charlottesville, VA 22908

 

References

 

1. Juniper EF, Kline PA, Ramsdale EH, Hargreave FE. Comparison of

the efficacy and side effects of aqueous steroid nasal spray

(budesonide) and allergen-injection therapy (Pollinex-R) in the

treatment of seasonal allergic rhinoconjunctivitis. J Allergy Clin

Immunol 1990;85:606-11.

Return to: Text

 

2. Abramson MJ, Puy RM, Weiner JM. Is allergen immunotherapy

effective in asthma? A meta-analysis of randomized controlled

trials. Am J Respir Crit Care Med 1995;151:969-74.

Return to: Text

------------------------------------------------------------------

To the Editor:

 

Barnes notes that few people with asthma have symptoms confined to

ragweed season. This phenomenon may reflect the fact that the

ragweed-pollen grain is approximately 20 microm in diameter. (1)

Consequently, ragweed-pollen grains are less likely to penetrate

past the glottis. Alternatively, the perennial allergens

house-dust mites and cat dander may be airborne in particles less

than 20 microm in diameter (2) and are more likely to enter the

bronchial tree.

 

Although Barnes writes that immunotherapy with dust-mite allergen

appears to be less effective than immunotherapy with seasonal

allergens, the clinical benefit of immunotherapy with a

standardized dust-mite extract has been demonstrated. (3) As

implied by Creticos et al., a double-blind, placebo-controlled

multicenter trial using standardized extracts of perennial

allergens, and possibly of allergens encountered during multiple

pollen seasons, would address the situations of most patients who

have allergic asthma and of many of the patients screened for the

study who did not meet the entry criteria.

 

Joel S. Klein, M.D.

9301 Golf Rd.

Des Plaines, IL 60016

 

References

 

1. Gutman AA, Bush RK. Allergens and other factors important in

atopic disease. In: Patterson R, Grammer LC, Greenberger PA, Zeiss

CR, eds. Allergic diseases: diagnosis and management. 4th ed.

Philadelphia: J.B. Lippincott, 1993:93-158.

Return to: Text

 

2. Platts-Mills TAE. Indoor allergens. In: Middleton E Jr, Reed

CE, Ellis EF, Adkinson NF Jr, Yunginger JW, Busse WW, eds.

Allergy: principles and practice. 4th ed. Vol. 1. St. Louis:

Mosby, 1993:514-28.

Return to: Text

 

3. Bousquet J, Hejjaoui A, Clauzel AM, et al. Specific

immunotherapy with a standardized Dermatophagoides pteronyssinus

extract. II. Prediction of efficacy of immunotherapy. J Allergy

Clin Immunol 1988;82:971-7.

Return to: Text

------------------------------------------------------------------

To the Editor:

 

Creticos et al. emphasized the importance of twice-daily peak flow

readings as "objective day-to-day assessments of the seriousness

of asthma." Our research casts serious doubt on the usefulness of

unmonitored peak flow readings and the accuracy of diaries. (1)

During a relatively short five-week study of 20 patients with

asthma, we compared the electronic memory of the peak flowmeter

with the written diary of each participant. Allowing a 10 percent

deviation in recording due to random error, we found that over 20

percent of the final week's recordings in the diaries were in

error. A tendency to inflate the peak expiratory flow rate

occurred. There were a substantial number of phantom readings in

which peak flow was recorded in the diary as having been measured

but was never actually measured. During a multiyear study, phantom

readings may lead to a regression toward the mean similar to the

profile of data obtained during the second year of the study by

Creticos et al.

 

The diaries' records of the use of antiinflammatory inhaler sprays

showed a similar pattern of inaccuracy, with 47.1 percent of all

base-line recordings off by more than 10 percent, and 57.9 percent

of all final-week recordings showing errors. There was a tendency

to record more medication use than actually occurred. Others have

also found marked inaccuracies in the reporting of inhaler use.

(2,3,4)

 

Considering the long time frame for the ragweed-immunotherapy

study and the limited sample size, it is likely that there was

some inaccuracy in the diary recordings that seriously undermined

the results. Whatever motivates a patient to report erroneous or

phantom recordings, inaccuracies are a serious methodologic threat

to studies that rely on the use of diaries.

 

Frank Chmelik, M.D.

Andrea Doughty, Ph.D.

University of Illinois College of Medicine

Rockford, IL 61107

 

References

 

1. Chmelik F, Doughty A. Objective measurements of compliance in

asthma treatment. Ann Allergy 1994;73:527-32.

Return to: Text

 

2. Spector SL, Kinsman R, Mawhinney H, et al. Compliance of

patients with an experimental aerosolized medication: implications

for controlled clinical trials. J Allergy Clin Immunol

1986;77:65-70.

Return to: Text

 

3. Mann M, Eliasson O, Patel K, ZuWallack RL. A comparison of the

effects of bid and qid dosing on compliance with inhaled

flunisolide. Chest 1992;101:496-9.

Return to: Text

 

4. Mann MC, Eliasson O, Patel K, ZuWallack RL. An evaluation of

severity-modulated compliance with q.i.d. dosing of inhaled

beclomethasone. Chest 1992;102:1342-6.

Return to: Text

 

-----------------------------------------------------------------------

The authors reply:

 

To the Editor:

 

Many people with asthma receive immunotherapy in an attempt to

desensitize them to their allergies. The introduction of

characterized and standardized allergen extracts has allowed a

precisely defined therapeutic dose to be calculated and

administered. (1,2)

 

We agree with Weiner et al. that the findings in the first year of

our study are more likely to represent the true effects of

immunotherapy. That these favorable changes were less pronounced

in the second year of treatment is consistent with a regression

toward the mean. The attrition in the placebo group -- secondary

to a poor response -- certainly reduced the statistical power of

our findings in the second treatment year. However, the group of

17 patients immunized for a third year continued to show a similar

magnitude of improvement in symptoms, peak flow, and medication

use, providing evidence that the improvement is not short-lived

but is persistent.

 

As do Chmelik and Doughty, we recognize the pitfalls inherent in

the use of daily monitoring of peak flow and diaries of medication

use. Even with carefully trained patients, uncontrolled variables

such as these require blinded observations in untreated control

patients. Were we to initiate another study with similar aims, we

would use microprocessor-based electronics for the peak flowmeters

and inhalation devices. These were not available at the time of

our study.

 

After treatment, there was a significant improvement in the

response to bronchial challenge to ragweed in the immunotherapy

group. This finding helps corroborate the measurable improvements

in peak flow in the immunotherapy group as compared with the

placebo group.

 

Klein questions the relevance of ragweed-induced asthma. Agarwal

et al. demonstrated that a considerable fraction of airborne

ragweed allergen exists as particles that are less than 10 microm

in diameter. (3) These aerosolized microparticles can easily reach

the lower airways and provoke symptoms of asthma.

 

Patients with allergies are commonly sensitive to multiple

aeroallergens. Our mandate was to study in detail the effects of

immunotherapy on a dominant seasonal allergen. Ragweed was chosen

because of the extensive work done to characterize and standardize

it. We are currently extending our initial observations in ragweed

asthma and studying the effectiveness of immunotherapy in adults

with asthma and multiple allergies.

 

Peter S. Creticos, M.D.

Philip S. Norman, M.D.

Johns Hopkins University School of Medicine

Baltimore, MD 21224

 

Charles Reed, M.D.

Mayo Clinic

Rochester, MN 55905

 

References

 

1. Malling H-J, Weeke B, eds. Position paper: immunotherapy.

Allergy 1993;48:Suppl 14:9-35.

Return to: Text

 

2. Creticos PS, ed. Immunotherapy: a practical guide to current

procedures. Milwaukee: American Academy of Allergy, Asthma and

Immunology, 1994.

Return to: Text

 

3. Agarwal MK, Swanson MC, Reed CE, Yunginger JW. Immunochemical

quantitation of airborne short ragweed, Alternaria, antigen E, and

Alt-1 allergens: a two-year prospective study. J Allergy Clin

Immunol 1983;72:40-5.

Return to: Text

------------------------------------------------------------------

To the Editor:

 

Portnoy and Finegold, representing the American College of

Allergy, Asthma and Immunology, suggest that I did not acknowledge

the beneficial effects of allergen immunotherapy reported by

Creticos et al. I clearly stated that there was an objective

beneficial effect during the first year of treatment, but I

pointed out that this effect was small and was not sustained in

the second year -- a conclusion that the authors also made.

Portnoy and Finegold also suggest that the small effect may be due

to an improvement in the placebo group. This is precisely the

reason for conducting placebo-controlled, double-blind trials in

diseases such as asthma, when large placebo effects may be

observed.

 

The relatively small effect of specific immunotherapy must be

compared with the high efficacy of inhaled glucocorticoids, which

are effective in all patients and have few or no serious side

effects at the doses required by most patients. (1) My statement

that the avoidance of allergens and drug therapy are the preferred

approach is based on the numerous national and international

guidelines for asthma therapy, including those of the most recent

National Heart, Lung, and Blood Institute-World Health

Organization Global Initiative in Asthma Management. (2)

 

Platts-Mills suggests that the continuing high rate of hospital

admissions in several countries implies that inhaled

corticosteroids are not effective. This is a curious

interpretation of the evidence. A striking finding in all

long-term controlled studies of inhaled corticosteroids is a

marked reduction in acute exacerbations and hospital admissions

for asthma. (1) This has not been demonstrated for specific

immunotherapy. As I stated, there is an urgent need for

comparative studies of immunotherapy and inhaled corticosteroids.

I cited the only study that I am aware of that compared topical

corticosteroid therapy with immunotherapy. Although Platts-Mills

implies that the allergen preparation used in that study is

ineffective, it was in widespread use for the treatment of hay

fever. He also refers to the high costs of inhaled

corticosteroids. Several detailed pharmacoeconomic analyses,

however, indicate that this treatment is the cheapest means of

managing asthma, since it markedly reduces hospital admissions and

the time lost from work. (3,4) Such data have not been provided

for immunotherapy.

 

I agree with Klein that ragweed immunotherapy may not be indicated

in many patients. The study by Creticos et al. illustrated how

difficult it is to find patients in whom it may be indicated. Most

patients with asthma have multiple skin-test responses, and

perennial allergens, such as house-dust mites and cat dander, are

much more important than seasonal allergens. However, studies of

specific immunotherapy with these allergens have generally been

disappointing. Indeed, a recent large, placebo-controlled trial of

multiple-allergen immunotherapy in children with asthma found that

immunotherapy was completely ineffective. (5,6,7)

 

Peter J. Barnes, D.M., D.Sc.

National Heart and Lung Institute

London SW3 6LY, United Kingdom

 

References

 

1. Barnes PJ, Pedersen S. Efficacy and safety of inhaled

corticosteroids in asthma. Am Rev Respir Dis 1993;148:S1-S26.

Return to: Text

 

2. Global strategy for asthma management and prevention. NHLBI/WHO

workshop report no. 95-3659. Geneva: World Health Organization,

1995:1-176.

Return to: Text

 

3. Rutten-van Molken MP, Van Doorslaer EK, Jansen MC, Kerstjens

HA, Rutten FF. Costs and effects of inhaled corticosteroids and

bronchodilators in asthma and chronic obstructive pulmonary

disease. Am J Respir Crit Care Med 1995;151:975-82.

Return to: Text

 

4. Barnes PJ, Jonsson B, Klim J. The costs of asthma. Eur Respir J

(in press).

Return to: Text

 

5. Adkinson F, Eggleston P, Goldstein E, et al. Trial of

immunotherapy for allergic asthma in children. I. Design and

methods. J Allergy Clin Immunol 1995;95:189. abstract.

Return to: Text

 

6. Adkinson F, Eggleston P, Goldstein E, et al. Trial of

immunotherapy for allergic asthma in children. II. Outcomes. J

Allergy Clin Immunol 1995;95:189. abstract.

Return to: Text

 

7. Adkinson F, Eggleston P, Goldstein E, et al. Trial of

immunotherapy for allergic asthma in children. III.

Considerations. J Allergy Clin Immunol 1995;95:189. abstract.

Return to: Text

 

Copyright ©1996 by the Massachusetts Medical Society

5. Local nasal immunotherapy for birch allergic rhinitis with extract

in powder form.

Title Abreviation: Clin Exp Allergy Date of Pub: 1995 Nov

Author: Andri L; Senna G; Andri G; Dama A; Givanni S; Betteli C; Dimitri

G; Falagiani P; Mezzelani P;

Issue/Part/Supplement: 11 Volume Issue: Pagination: 1092-9

25

MESH Headings: Administration, Intranasal; Adult; Allergens (AE/*TU);

Female; Hay Fever (*TH); Human; Immunotherapy (*/MT); Male; Middle Age;

Plant Extracts (AD/AE/*TU); Powders; Seasons; Support, Non-U.S. Gov't;

Trees (*IM); -RN-;

Journal Title Code: CEB Publication Type: JOURNAL ARTICLE

Date of Entry: 960321N Entry Month: 9605

Country: ENGLAND Index Priority: 2

Language: Eng Unique Identifier: 96161000

Unique Identifier: 96161000 ISSN: 0954-7894

Abstract: BACKGROUND: Traditional subcutaneous immunotherapy has been

proved effective in birch pollenosis. It has, however, some drawbacks as

systemic reactions, which are rare but important. Local nasal

immunotherapy (LNIT) represents a potential safer route of allergen

administration. OBJECTIVE: To study the clinical efficacy and safety of

local nasal immunotherapy by means of an extract in powder form as

treatment of birch allergic rhinitis. METHODS: Thirty birch allergic

patients have been selected on the basis of a positive history, skin test,

radioallergosorbent test assay (RAST) and specific nasal challenge. Two 15

patient groups were randomly assigned to the active treatment or to the

placebo one. Treatment lasted 22 weeks (14 for the build-up phase and

eight for maintenance period) and symptoms were recorded during the

treatment and the birch pollen season. RESULTS: The clinical efficacy of

LNIT is suggested by a significant reduction of medication score only in

the treated group during the pollen season, although the symptom score was

significantly lower in the treated group for 1 week only. Moreover, a

significant increase of specific nasal threshold dose was observed after

treatment only in the active treated group. Mild adverse reaction to LNIT,

limited to the upper respiratory tract, were reported during the treatment

in the active group, but they did not interfere with LNIT schedule. No

asthmatic or systemic reaction were observed. CONCLUSIONS: This study

indicates that LNIT with allergen in powder form has proven clinically

effective in the treatment of birch allergic rhinitis. Further studies are

needed to establish whether this treatment can be considered a real

alternative to the traditional subcutaneous immunotherapy in birch

allergic rhinitis.

Abstract By: Author

Address: Unit of Clinical Allergology, Verona General Hospital, Italy.

6. Possible induction of food allergy during mite immunotherapy.

Title Abreviation: Allergy Date of Pub: 1996 Feb

Author: van Ree R; Antonicelli L; Akkerdaas JH; Garritani MS; Aalberse RC;

Bonifazi F;

Issue/Part/Supplement: 2 Volume Issue: Pagination: 108-13

51

MESH Headings: Allergens*; Animal; Cross Reactions*; Food

Hypersensitivity*; Human; IgE*; Immunoblotting*; Immunotherapy*; Mites*;

Radioallergosorbent Test*; Shrimp*; Skin Tests*; Snails*; Tissue

Extracts*; Tropomyosin*; -PG-;

Journal Title Code: 39C Publication Type: JOURNAL ARTICLE

Date of Entry: 961002N Entry Month: 9612

Country: DENMARK Index Priority: 2

Language: Eng Unique Identifier: 96350662

Unique Identifier: 96350662 ISSN: 0105-4538

Abstract: Sera of 17 patients receiving immunotherapy for house-dust mite

allergy were tested for IgE antibodies against snail and shrimp. Serum

samples were taken at the start of immunotherapy and 14-20 months later.

While the average IgE response to mite, Der p 1, and Der p 2 did not alter

significantly, the average response to snail showed a significant

increase. This included two conversions from negative to strongly

positive. These novel IgE antibodies against snail were shown to be

cross-reactive with mite. Three patients had a positive RAST for shrimp.

For one of them, a strong increase of IgE against shrimp (and snail) was

observed. In 2/3 snail/shrimp-positive sera, IgE antibodies against the

cross-reactive allergen tropomyosin from mite, snail, and shrimp were

demonstrated. A clear IgE response to snail (> 10% binding in a snail

RAST) was confirmed by a positive skin prick test (SPT) for 6/10 patients.

The two patients with antitropomyosin IgE also had a positive SPT for

shrimp, and demonstrated the oral allergy syndrome (OAS) after eating

shrimp. The observations in this study indicate that house-dust mite

immunotherapy is accompanied by the induction of IgE against foods,

including tropomyosin-reactive IgE. Food allergy (OAS) was observed in

patients that had IgE antibodies against this cross-reactive allergen. In

conclusion, induction of IgE during mite immunotherapy might occasionally

cause allergy to foods of invertebrate animal origin.

Abstract By: Author

Address: Central Laboratory, The Netherlands Red Cross Blood Transfusion

Service, Amsterdam, The Netherlands.

7. Alternative routes for allergen-specific immunotherapy.

Author

Passalacqua_G; Canonica_GW

Address

Department of Internal Medicine, Genoa University, Italy.

Source

J Investig Allergol Clin Immunol, 1996 Mar-Apr, 6:2, 81-7

Abstract

The alternative routes for allergen-specific immunotherapy (oral,

sublingual, intranasal) have the overall aim of minimizing or avoiding

the possible side-effects caused by the injectory route, and of making

the treatment more convenient and acceptable for the patients. The

clinical efficacy and the safety of the alternative routes have been

clearly demonstrated in many controlled studies for the most common

inhalant allergens. The oral routes appear particularly suitable for

children and patients with unsatisfactory compliance with the injectory

route. On the other hand, nasal immunotherapy, because of its peculiar

administration technique, requires a careful choice of well-trained

adult patients. In conclusion, the good tolerability, safety and

socioeconomic benefits strongly support the use of alternative routes

as valid therapeutic options for the treatment of respiratory allergy.

Language of Publication

English

Unique Identifier

96330862

8. Effects of immunotherapy on symptoms, PEFR, spirometry, and airway

responsiveness in patients with allergic asthma to house-dust mites (D.

pteronyssinus) on inhaled steroid therapy.

Author

Costa_JC; Plácido_JL; Silva_JP; Delgado_L; Vaz_M

Address

Department of Allergology and Clinical Immunology, H.S. João, Porto,

Portugal.

Source

Allergy, 1996 Apr, 51:4, 238-44

Abstract

The present study was designed to investigate the effects of

immunotherapy (IT) with an extract of Dermatophagoides pteronyssinus

(Alergo-Merck Depot) during a 27-month period in patients with allergic

asthma to house-dust mites. We included 11 patients (mean age 18 years)

treated with a combination of IT and inhaled beclomethasone

dipropionate (BDP) in comparison to another 11 (mean age 22 years)

treated with BDP alone. We evaluated symptom scores, salbutamol use,

peak expiratory flow rates (PEFR), spirometry, and bronchial

hyperresponsiveness (BHR) during 18 months of therapy with BDP and in

the 9 months after BDP interruption. The two kinds of treatment were

efficient and comparable in relation to symptom score, salbutamol use,

morning PEFR, FVC, and FEV1, but patients treated with IT and BDP had a

faster improvement of BHR and PEFR variability. The interruption of BDP

after 18 months of therapy was linked to an impairment of all end

points, which were more pronounced in patients previously treated only

with BDP. These findings suggest that in selected asthmatic patients

allergic to house-dust mites, the association of IT and BDP is more

effective than therapy with this inhaled steroid alone due to a faster

and more striking improvement during the first months of treatment and

to a lower rate of relapse after the interruption of therapy with BDP.

Language of Publication

English

Unique Identifier

96385060

9. Preseasonal intranasal immunotherapy in birch-alder allergic

rhinitis. A double-blind study.

Title Abreviation: Allergy Date of Pub: 1996 May

Author: Cirla AM; Sforza N; Roffi GP; Alessandrini A; Stanizzi R; Dorigo

N; Sala E; Della Torre F;

Issue/Part/Supplement: 5 Volume Pagination: 299-305

Issue: 51

MESH Headings: Administration, Intranasal; Adolescence; Adult;

Double-Blind Method; Drug Administration Schedule; Female; Hay Fever

(*TH); Human; Immunotherapy (*MT); Male; Pollen (*IM); Seasons; Trees

(*IM); -AA-;

Journal Title Code: 39C Publication Type: CLINICAL TRIAL

Date of Entry: 970204N Entry Month: 9704

Country: DENMARK Index Priority: 2

Language: Eng Unique Identifier: 96433346

Unique Identifier: 96433346 ISSN: 0105-4538

Abstract: A double-blind, placebo-controlled study was carried out to test

the clinical efficacy and safety of local nasal immunotherapy (LNIT) in

powder form. Twenty-two patients suffering from allergic rhinitis strictly

associated with early spring symptoms, with positive skin prick tests and

RAST for birch-alder, all responders to a specific nasal provocation test

(NPT), received randomly active or placebo treatment for 4 months.

Immunotherapy consisted of administration of a set of capsules containing

progressively increasing amounts of birch (Betula pendula) and speckled

alder (Alnus incana) allergens in powder form with controlled

granulometry. The active (birch-alder) and placebo (lactose) group

completed the treatment according to a similar schedule. During the pollen

season (March-April), the patients who took the active treatment reported

less sneezing and rhinorrhea than the placebo group, on the basis of a

symptoms score, and the differences were statistically significant; the

need for drugs (terfenadine) was also significantly reduced. These

findings agreed well with the results of specific NPT after the treatment;

only patients in the active group had a higher threshold dose of nasal

specific reactivity to birch-alder allergens than in tests before the

LNIT.

Abstract By: Author

Address: Istituti Ospitalieri di Cremona, Center for Environmental

Allergy, Cremona, Italy.

10. Immunotherapy with a standardized Dermatophagoides pteronyssinus

extract. V. Duration of the efficacy of immunotherapy after its

cessation.

Author

Des_Roches_A; Paradis_L; Knani_J; Hejjaoui_A; Dhivert_H; Chanez_P;

Bousquet_J

Address

Service des Maladies Respiratoires, Hôpital Arnaud de Villeneuve,

Montpellier, France.

Source

Allergy, 1996 Jun, 51:6, 430-3

Abstract

Specific immunotherapy (SIT) using a standardized mite extract is

effective and safe when administered under optimal conditions. However,

the duration of its effectiveness after cessation of treatment remains

unknown. Forty asthmatic subjects who had received SIT with a

standardized Dermatophagoides pteronyssinus (Der p) extract under the

same protocol were studied. All had received SIT for a period of 12-96

months and were not receiving pharmacologic treatment. The FEV1 was

within normal range in all patients. After cessation of treatment,

patients were followed for up to 3 years at 6-month intervals. The

patient was considered to have relapsed when symptoms of asthma and/or

rhinitis occurred and/or when pulmonary function tests were impaired.

Skin tests with increasing concentrations of Der p were carried out

before and at the end of SIT. Forty-five percent of the patients did

not relapse. The duration of efficacy of SIT was related to the

duration of SIT itself (P < 0.04). Most patients who did not relapse

had a decrease in skin test reactivity at the end of SIT, whereas most

patients who relapsed did not show any change (P < 0.003). The duration

of efficacy of SIT after its cessation depends upon the duration of SIT

and may be predicted by the effect of SIT on skin tests.

Language of Publication

English

Unique Identifier

96434745

11. Efficacy of immunotherapy to ragweed antigen tested by controlled

antigen exposure.

Title Abreviation: Ann Allergy Asthma

Immunol Date of Pub: 1996 Jul

Author: Donovan JP; Buckeridge DL; Briscoe MP; Clark RH; Day JH;

Issue/Part/Supplement: 1 Volume Issue: Pagination: 74-80

77

MESH Headings: Adolescence*; Adult*; Aged*; Allergens*; Environment,

Controlled*; Female; Hay Fever*; Human; Immunotherapy, Active*; Male;

Middle Age*; Plant Proteins*; Pollen*; Support, Non-U.S. Gov't; -PG-;

Journal Title Code: CBM Publication Type: CLINICAL TRIAL

Date of Entry: 960910N Entry Month: 9611

Country: UNITED STATES Index Priority: 1

Language: Eng Unique Identifier: 96302215

Unique Identifier: 96302215 ISSN: 1081-1206

Abstract: BACKGROUND: Immunotherapy is a recognized component in the

management of allergic rhinitis. Its efficacy has been evaluated in a

number of clinical field trials. These methods of evaluation are limited

by control of antigen exposure. OBJECTIVE: A study was designed to

evaluate the efficacy of immunotherapy in ragweed-induced

rhinoconjunctivitis using an environmental exposure unit. METHODS:

Forty-three subjects were grouped into (1) immunotherapy group:

ragweed-allergic subjects on maintenance ragweed immunotherapy for at

least 2 years (N = 16), (2) positive control group: ragweed-allergic

subjects who had never received immunotherapy (n = 16), and (3) negative

control group: ragweed-nonallergic subjects (N = 11). Ragweed specific

skin tests and ragweed IgE levels were obtained prior to exposure. The

study was done in a room where levels of 2,500 to 3,000 grains m3 of

ragweed were maintained over three hours. Symptoms were recorded every 15

minutes. RESULTS: Nasal symptoms in the immunotherapy group were

significantly less than in the positive control group after 45 minutes (P

= .025). Significant differences were not observed for ocular symptoms.

Combined nasal and ocular scores were 50% less in the immunotherapy group

than in the positive control group by 75 minutes (P = .039).

Ragweed-specific skin tests and IgE were significantly less in the

immunotherapy group than in the positive control group.

Rhinoconjunctivitis symptoms in the negative control group were absent

throughout. CONCLUSIONS: Controlled ragweed pollen exposure in this

setting demonstrated that ragweed immunotherapy significantly reduced

symptoms of ragweed-allergic rhinitis but had no significant effect on

ocular symptoms. This system presents opportunities for additional studies

on immunotherapy for allergic respiratory conditions.

Abstract By: Author

Address: Division of Allergy and Immunology, Kingston General Hospital,

Ontario, Canada.

12. Allergen-specific low-dose immunotherapy in perennial allergic

rhinitis: a double-blind placebo-controlled crossover study.

Author

Radcliffe_MJ; Lampe_FC; Brostoff_J

Address

University of Southampton, England.

Source

J Investig Allergol Clin Immunol, 1996 Jul-Aug, 6:4, 242-7

Abstract

In a double-blind placebo-controlled crossover study, 36 adults with

perennial allergic rhinitis were treated with daily subcutaneous

injections of inhalant allergens, the doses of which had been

predetermined by intradermal testing. The dose chosen for each allergen

was the maximum intradermally tolerated dose (MITD) of that allergen,

defined as 0.05 ml of the strongest concentration in a 1:5 dilution

series which did not produce a positive wheal. Of the 27 who expressed

a preference, 21 (78%) preferred the active preparation and six (22%)

the placebo (p = 0.006). Significant symptom relief was apparent on an

analysis of total rhinitis symptom scores (p = 0.006), nasal blockage

(p = 0.02), nasal discharge (p = 0.006), postnasal drip (p = 0.02) and

anosmia (p = 0.02). These results support the validity of

allergen-specific low-dose immunotherapy using the MITD.

Language of Publication

English

Unique Identifier

97001509

13. Sublingual versus injective immunotherapy in grass pollen allergic

patients: a double blind (double dummy) study [see comments]

Author

Quirino_T; Iemoli_E; Siciliani_E; Parmiani_S; Milazzo_F

Address

Servizio di Allergologia Ospedale L. Sacco, Milan, Italy.

Source

Clin Exp Allergy, 1996 Nov, 26:11, 1253-61

Abstract

BACKGROUND: Injective immunotherapy is a well-known and recognized

treatment for allergic diseases, but its safety has been questioned

during recent years. Alternative administration routes have been

proposed and there is a growing interest and experience in sublingual

therapy. The safety of alternative routes is nonetheless a real

advantage, so long as it is not counterbalanced by a loss of clinical

benefit. OBJECTIVE: We have compared the efficacy of the same

biologically standardized grass pollen extract administered through the

injective or the sublingual route, in a group of 20 patients followed

for two pollen seasons. METHODS: Both therapies were administered for

12 months according to a double-blind (double-dummy) plan; at the end

of the trial the cumulative dosage of the sublingual therapy was 2.4

times higher than that of the injective therapy. Data about skin

reactivity, symptoms and drugs scores during the pollen season, as well

as total specific IgG and specific IgG4, during and after the trial,

were obtained. RESULTS: Our data show that sublingual and injective

therapy are equally effective according to subjective clinical

parameters, with a statistically highly significant reduction of

symptoms and drugs (P = 0.002 for symptoms and drugs in SLIT-treated

patients; P = 0.002 for symptoms and P = 0.0039 for drugs in patients

given injections). On the other hand, objective parameters (total

specific IgG, specific IgG4, skin reactivity) changed only in patients

treated with active injective therapy, with P < 0.001, P < 0.001 and P

= 0.021, respectively. CONCLUSIONS: The discrepancies observed could be

interpreted as a consequence of different mechanisms of actin of the

two therapies or to the lack of close relationships between the

clinical and the objective parameters which were considered here.

Language of Publication

English

Unique Identifier

97113734

14. The efficacy of E.P.D., a new immunotherapy, in the treatment of

allergic diseases in children.

Author

Caramia_G; Franceschini_F; Cimarelli_ZA; Ciucchi_MS; Gagliardini_R;

Ruffini_E

Address

Division Pediatric, Salesi Hospital of Ancona, Italy.

Source

Allerg Immunol (Paris), 1996 Nov, 28:9, 308-10

Abstract

A double blind study was made on a group of 35 children, 8 of whom were

allergic to Grass and 27 allergic to Pteronyssinus and Farinae

Dermatophagoides. We verified the efficacy and tolerability of a new

immunotherapy called E.P.D. (Enzyme Potentiated Desensitization). This

particular immunotherapy consists in an intradermal injection of a mix

made up of an allergic solution at extremely low doses and an enzyme,

beta-glucuronidase. The vaccine is administered once a year, two weeks

before pollen peaks for children with seasonal allergies and two times

a year, in February and November, for children with non-seasonal

allergies (Dermatophagoides). The results, statistically analyzed on

the basis of a symptoms score, showed good clinical efficacy in

patients affected by both seasonal and non-seasonal allergies. Due to

the clinical effectiveness, easy administration and excellent

tolerability of the immunotherapy, E.P.D. is particularly suited for

treating or reducing allergic symptoms in allergic children.

Language of Publication

English

Unique Identifier

97139645

15. A Controlled Trial of Immunotherapy for Asthma in Allergic Children

N. Franklin Adkinson, Jr., Peyton A. Eggleston, Donald Eney, Eugene O.

Goldstein, Kenneth C. Schuberth, John R. Bacon, Robert G. Hamilton, Michael

E. Weiss, Hasan Arshad, Curtis L. Meinert, James Tonascia, Barbara Wheeler

Abstract

 

Background. Injections of allergens are widely prescribed for

patients with asthma, but little is known about the effectiveness

of immunotherapy.

 

Methods. We conducted a double-blind, placebo-controlled trial of

multiple-allergen immunotherapy in 121 allergic children with

moderate-to-severe, perennial (year-round) asthma. The children,

who required daily medication for their asthma, were randomly

assigned to receive subcutaneous injections of either a mixture of

up to seven aeroallergen extracts or a placebo. Maintenance

injections were continued for 18 months or longer. Medications

were adjusted every two to three weeks on the basis of peak flow

rates and symptoms. The principal outcome was the daily medication

score. Bronchial sensitivity to methacholine (the concentration

provoking a 20 percent decrease in the forced expiratory volume in

one second [PC20]) was measured twice yearly.

 

Results. The median medication score declined from 5.4 to 4.9 in

the immunotherapy group (P<0.001) and from 5.2 to 5.0 in the

placebo group (P<0.001), but there was no significant difference

between the groups (P>0.6). The number of days on which oral

corticosteroids were used was similar in the two groups. Partial

or complete remission of asthma occurred in 31 percent of the

immunotherapy group and in 28 percent of the placebo group

(P>0.5). There was no difference between the groups in the use of

medical care, symptoms, or peak flow rates. The median PC20

increased significantly in both groups, but again with no

difference between the two groups.

 

Conclusions. Immunotherapy with injections of allergens for over

two years was of no discernible benefit in allergic children with

perennial asthma who were receiving appropriate medical treatment.

(N Engl J Med 1997;336:324-31.)

Source Information

From the Asthma and Allergy Center and the Department of Medicine

(N.F.A., R.G.H., M.E.W., H.A., B.W.) and the Department of

Pediatrics (P.A.E., D.E., E.O.G., K.C.S., J.R.B.), Johns Hopkins

University School of Medicine, and the Departments of

Biostatistics and Epidemiology, Johns Hopkins School of Hygiene

and Public Health (C.L.M., J.T.) -- both in Baltimore. Address

reprint requests to Dr. Adkinson at 5501 Hopkins Bayview Cir.,

Baltimore, MD 21224-6801.

BULLETIN!

January 29, 1997

From: Betty Wray, M.D. ACAAI President

Contact: Jo Ann Faber (847) 427-1200

Subject: Article on immunotherapy in The New England Journal of Medicine

 

The article published in the January 30 issue of The New England Journal of

Medicine, "A Controlled Trial of Immunotherapy for Asthma in Allergic

Children," by N. Franklin Adkinson, Jr., M.D., and others, states the

following:

 

"Immunotherapy with injections of allergens for over two years was of

no discernible benefit in allergic children with perennial asthma who

were receiving appropriate medical treatment."

 

These findings do not reflect the experience of allergists-immunologists in

clinical practice and are inconsistent with the majority of previously

published studies in children and adults. The authors offer several possible

explanations for the absence of significant improvement with immunotherapy

in these children with moderate-to-severe asthma. We offer additional

possible reasons for the study's results. These include the following:

 

1. Although the investigators sampled the dust in patient's homes, they

give no results of that sampling, nor an indication as to which

patients actually carried out dust precautions, such as enclosing

mattress and pillows in impermeable covers. If more patients randomized

to the placebo group complied with the recommendations, that would

account for their improvement. The authors state that substantial

improvements in the control of asthma occurred in many children even

before randomization. Was this factor considered in the randomization

process?

2. Immunologic parameters in the immunotherapy-treated group improved as

anticipated. However, the extracts contained only seven allergens or

less. It is not clear that the investigators evaluated for sensitivity

to the numerous additional allergens in the patients' environment, such

as cockroach, other tree and weed pollens, or other molds such as

penicillium, fusarium, epicoccum. These patients may have been

sensitive to multiple allergens that were not included in the testing

or treatment. Most allergic patients are reactive to more than seven

allergens; immunotherapy that does not include all the relevant

allergens cannot be expected to be maximally effective.

3. The immunotherapy group contained slightly more males and more blacks.

Could this indicate that more inner city asthmatics were in this group?

4. As the authors indicate, this study should not be interpreted as

indicating that allergen immunotherapy is ineffective. Immunotherapy

may be useful in populations of asthmatics who are uncontrolled with

environmental measures and pharmocotherapy. In addition, immunotherapy

may be useful in the prevention of development of asthma in children

with allergic rhinitis as indicated by Johnstone in 1968 and as is

currently being addressed in an ongoing multicenter, randomized,

prospective European study (Jacobsen L. Clin. Exp. Allergy 1996; 26:

80-85). A meta-analysis which indicates that 33 studies with negative

results would be required to negate the published results of these

positive studies. (Abramson, MJ et al, Am J Respir Crit Care Med 1995;

151: 969-974).

5. There are a number of studies that have shown when we look at animal

danders or dust mites we can measure the patients getting better, we

can measure immunologic parameters, and we can see that immunotherapy

is highly effective. The problem with the Adkinson study is they were

using multiple antigens, and they may not have been hitting all the

allergens affecting the patients. We don't know if the groups that had

seasonal allergies did better. There's an omission of such allergens,

like cockroach, mouse and rat, that are prevalent in inner cities.

6. The investigators measured peak flows and not spirometry, which is more

accurate. They measured symptom scores, which can be subject to patient

manipulation.

7. The selection of the patients in the study used a sicker asthmatic

population than one might select for immunotherapy patients in an

office setting, and hence appears less representative.

 

Further studies of immunotherapy based on the history of the patients'

environmental exposures and appropriate skin testing are needed to evaluate

this valuable form of therapy and to define the patients who will benefit

the most from this form of treatment.

 

----------------------------------------------------------------------------

 

Also see: Expert Care and Immunotherapy for Asthma, Allergists Caution

Parents: Don't Stop Children's Allergy Shots

----------------------------------------------------------------------------

 

For more information, please contact:

American College of Allergy, Asthma & Immunology

85 West Algonquin Road, Suite 550

Arlington Heights, IL 60005

Phone: (847) 427-1200 Fax: (847) 427-1294

 

Copyright © 1997; The American College of Allergy, Asthma & Immunology

Most recent update: January 31, 1997

For more information or to send comments contact ACAAI Executive Office

 

wkd 1/30/97

The January 30, 1997 issue of the New England Journal of Medicine

contained an article on immunotherapy in children that is receiving local

and national attention. Adkinson NF, et al. A Controlled Trial of

Immunotherapy for Asthma in Allergic Children. NEJM 1997;336:324-31.

 

The Executive Committee of the AAAAI comments as follows:

 

1.This article was carefully done by an excellent group of allergist

investigators. There were some conditions applied to the study which

may explain why the findings disagree with many other studies which

have demonstrated that immunotherapy in allergic asthma is both

effective and beneficial.

 

2.In this study, children in both the immunotherapy and placebo groups

did very well, with remissions experienced by 31% of the subjects.

While those children receiving immunotherapy did somewhat better

than the control group, the differences were not statistically

significant. These data demonstrate that expert asthma care provided

by allergists results in gratifying reduction in asthma.

 

3.Patients were very carefully monitored in this study. In fact,

patients were seen by a physician every 2-3 weeks throughout the

study with an astounding 90% compliance rate. Thus, this group of

patients was provided with continuous, effective, expert care by the

allergists. That care, combined with extensive patient education,

allergen avoidance techniques, monitoring, and appropriate use of

effective medications available for the treatment of asthma, led to

improvement in their disease. The further addition of immunotherapy

helped, but did not achieve statistical significance.

 

4.While the patients received adequate doses of allergens, and

demonstrated appropriate immunologic responses to those allergens,

many critical allergens were not employed. In real life, patients

receiving immunotherapy receive a wide variety of perennial and

seasonal allergens to which they are allergic, and which were not

included in this study.

 

5.Therefore, we believe that this study confirms that expert asthma

care provided by allergists results in excellent improvements in

asthma, and in many instances this care can induce a remission in

asthma symptoms. This study clearly shows that the excellent

medications available today are effective at managing asthma

symptoms, when used appropriately by knowledgeable allergists.

 

Immunotherapy is the only treatment available today that has the potential

to suppress the allergic mechanism and to reduce the underlying cause of

allergic asthma. Many other studies have unequivocally shown that properly

administered immunotherapy reduces both asthma symptoms and the need

for concomitant medications. It would be unfortunate if the results of the

NEJM study were interpreted to indicate that immunotherapy is not helpful

in the management of asthma.

 

The American Academy of Allergy, Asthma and Immunology believes that

proper management of asthma includes identifying the underlying causes

for asthma, educating the patient in allergen avoidance techniques and

employing pharmacotherapy appropriately. Immunotherapy is appropriate in

those patients who have unequivocal allergic disease, cannot adequately

avoid the allergens to which they are sensitive, and are not adequately

managed pharmacologically. We believe that this approach to asthma

management will result in both short-range and long-range improvement in

patients' asthma, and that this approach is consistent with real life

situations and today's medical climate.

---

16. Immunotherapy with a standardized Dermatophagoides pteronyssinusextract. VI.

Specific immunotherapy prevents the onset of new sensitizations in children

Anne Des Roches, MD,a Louis Paradis, MD,a Jean-Luc Menardo, MD,a Stéphane

Bouges, MD,b Jean-Pierre Daurés, MD,a and Jean Bousquet, MDa

Montpellier and Nîmes, France

Background: The natural history of allergic sensitization is

complex and poorly understood. A prospective nonrandomized study

was carried out in a population of asthmatic children younger than

6 years of age whose only allergic sensitivity was to house dust

mites (HDMs).

Objectives: The study was designed to determine whether specific

immunotherapy (SIT) with standardized allergen extracts could

prevent the development of new sensitizations over a 3-year

follow-up survey.

Methods: We studied 22 children monosensitized to HDM who were

receiving SIT with standardized allergen extracts and 22 other

age-matched control subjects who were monosensitized to HDM. The

initial investigation included a full clinical history, skin tests

with a panel of standardized allergens, and the measurement of

allergen-specific IgE, depending on the results of skin tests.

Children were followed up on an annual basis for 3 years, and the

development of new sensitizations in each group was recorded.

Results: Ten of 22 children monosensitized to HDM who were

receiving SIT did not have new sensitivities compared with zero of

22 children in the control group (p = 0.001, chi square test).

Conclusions: This study suggests that SIT in children

monosensitized to HDM alters the natural course of allergy in

preventing the development of new sensitizations. ( J Allergy Clin Immunol 1997;99:450-453)

 

Author and Reprint Information

From aService des Maladies Respiratoires, Hôpital Arnaud de

Villeneuve, Montpellier; and bDépartement d'Information Médicale

et Biostatistiques, CHU Gaston, Doumergue, Nîmes.

Received for publication July 1, 1996; revised Sept. 10, 1996;

accepted for publication Sept. 11, 1996.

Individual reprint requests: Jean Bousquet, MD, Hôpital Arnaud de

Villeneuve, 34295-Montpellier-Cedex 5, France.

Manuscript number: 1/1/77910

Copyright Clearance Center number: 0091-6749/97 $5.00 + 0

1. Study on changes in the level of serum IL-4 and soluble CD 23(s-CD23)

with immunotherapy in nasal allergy patients.

Author

Ito_H; Suzuki_M; Mamiya_S; Takagi_I; Baba_S

Address

Department of Otorhinolaryngology, Nagoya City University Medical

School, Japan.

Source

Acta Otolaryngol Suppl (Stockh), 1996, 525:, 98-104

Abstract

In type I allergy such as allergic rhinitis, not only immunocytes but

also interleukin 4 (IL-4) and other cytokines are significant factors.

In the present study we explored the course of change in IL-4 in the

sera of allergic rhinitis patients upon immunotherapy. Assays of serum

IL-4 were performed by the chemiluminescence sandwich enzyme

immunoassay using

AMPPD(3-(2'-spirodamantane)-4-methoxy-4-(3'-phophoryloxy+ ++)

phenyl-1,2-dioxetane). The results indicated that immunotherapy reduced

the IL-4 level from the pre-treatment baseline but not significantly.

However, as far as good responses to the therapy are concerned a

significant decrease in IL-4 was seen, and s-CD23, assayed at the same

time, was also significantly decreased by immunotherapy.

Language of Publication

English

Unique Identifier

97064730

2. Mite-specific induction of interleukin-2 receptor on T lymphocytes from

children with mite-sensitive asthma: modified immune response with

immunotherapy.

Author

Bonno_M; Fujisawa_T; Iguchi_K; Uchida_Y; Kamiya_H; Komada_Y; Sakurai_M

Address

Department of Pediatrics, Mie National Hospital, Japan.

Source

J Allergy Clin Immunol, 1996 Feb, 97:2, 680-8

Abstract

BACKGROUND: The efficacy of immunotherapy is still controversial. To

elucidate the mechanisms of immunotherapy, we studied mite-specific

induction of IL-2 receptor (IL-2R) expression on T lymphocytes from

children with mite-sensitive asthma. METHODS: Peripheral blood

mononuclear cells were obtained from 28 children with mite-sensitive

asthma: 13 had never received house dust immunotherapy

(nonimmunotherapy group), 15 had been receiving house dust

immunotherapy at the time of the study (immunotherapy group). After a

6-day culture with or without Dermatophagoides farinae (Df) antigen,

the expression of IL-2Rp55 (CD25) and p75 on CD4+ or CD8+ T lymphocytes

was measured by flow cytometry. RESULTS: The nonimmunotherapy group

showed significant Df-specific CD25 induction on CD4+ T lymphocytes

(delta CD4+ CD25+) but little induction on CD8+ T lymphocytes (delta

CD8+ CD25+). delta CD4+ CD25+ was correlated with the severity of the

disease. In the immunotherapy group delta CD8+ CD25+ was significantly

higher than in the nonimmunotherapy group or in normal subjects and

correlated with Df-specific IgG4 and cumulative doses of house dust

extract, whereas delta CD4+ CD25+ was similar in the nonimmunotherapy

and the immunotherapy groups. IL-2Rp75 was not induced either on CD4+

or CD8+ T lymphocytes. CONCLUSIONS: Our data suggest that house dust

immunotherapy may have induced Df-specific CD8+ T lymphocytes in

patients with mite-sensitive asthma and that the efficacy of

immunotherapy may be attributed to the generation of Df-specific CD8+ T

lymphocytes.

Language of Publication

English

Unique Identifier

96191250

3. Evaluation of household dust mite exposure and levels of specific

IgE and IgG antibodies in asthmatic patients enrolled in a trial of

immunotherapy.

Title Abreviation: J Allergy Clin

Immunol Date of Pub: 1996 May

Author: Rose G; Arlian L; Bernstein D; Grant A; Lopez M; Metzger J;

Wasserman S; Platts-Mills TA;

Issue/Part/Supplement: 5 Volume Pagination: 1071-8

Issue: 97

MESH Headings: Adolescence*; Adult*; Air Pollution, Indoor*; Animal;

Antibody Specificity*; Asthma*; Cats*; Dust*; Female; Glycoproteins*;

Human; IgE*; IgG*; Immunization*; Male; Middle Age*; Mites*; Skin Tests*;

Support, U.S. Gov't, P.H.S.; -PG-;

Journal Title Code: H53 Publication Type: JOURNAL ARTICLE

Date of Entry: 960625N Entry Month: 9608

Country: UNITED STATES Index Priority: 1

Language: Eng Unique Identifier: 96212665

Unique Identifier:

96212665 ISSN: 0091-6749

Abstract: BACKGROUND: Monitoring the response to immunotherapy entails

understanding exposure to relevant allergens. For the major indoor

allergens, this requires sampling of dust from the patient's house. The

objectives of this study were to measure indoor allergen levels during a

controlled trial of dust mite immunotherapy for asthma and to relate these

results to serum antibody levels. METHODS: Eighty-eight asthmatic patients

with mite allergy from seven geographic areas in the United States were

enrolled in and completed a course of immunotherapy with Dermatophagoides

extract or placebo control. Sensitization was evaluated by quantitative

measurements of IgG and IgE antibodies. Dust samples were assayed for

group I mite (Der p 1 and Der f 1), cat (Fel d 1), and cockroach (Bla g 1)

allergens by monoclonal antibody-based ELISA. RESULTS: Over the 4 years of

the study, each of the houses had at least one sample that contained more

than 2 micrograms of group I mite allergen per gram of dust. Mean mite

allergen levels, however, varied over a wide range, from 0.2 microgram/gm

or less to more than 50 micrograms/gm. IgE antibodies to mite were present

in sera from 78% of the patients, whereas IgE antibodies to cat and

cockroach allergens were found in sera from 34% and 11% of patients,

respectively. Sixty-four percent of the patients had exposure and

sensitization to mite, whereas the comparable figure for each of the other

allergens was 5%. CONCLUSIONS: Examination of the results suggested that

allergen exposure, relative to a trial of immunotherapy, could be

expressed as (1) the maximum level found in the house, (2) the percentage

of sites having greater than 2 micrograms/gm, or (3) the mean value at the

site with the maximum level. This report provides a background for

evaluating the clinical results of immunotherapy in these patients and a

model for the way in which sensitization and exposure should be monitored

in studies of this kind.

Abstract By: Author

Address: Division of Allergy and Clinical Immunology, University of

Virginia Medical Center, Charlottesville 22908, USA.

4. Measurement of serum levels of eosinophil cationic protein to monitor

patients with seasonal respiratory allergy induced by Parietaria pollen

(treated and untreated with specific immunotherapy).

Author

D'Amato_G; Liccardi_G; Russo_M; Saggese_M; D'Amato_M

Address

Department of Chest Diseases, Hospital A. Cardarelli, Naples, Italy.

Source

Allergy, 1996 Apr, 51:4, 245-50

Abstract

This trial studied the behavior of a marker of eosinophilic

inflammation, eosinophil cationic protein (ECP), in the peripheral

blood of two groups of subjects with seasonal allergic respiratory

symptoms (rhinitis and mild bronchial asthma) induced by pollen

allergens of Parietaria judaica (P.j.) (one group treated and another

untreated with specific immunotherapy [SIT]), to determine what

contribution these serial measurements might provide, in comparison

with various other tools now available for pollinosis monitoring. In a

previously randomized order, we selected 25 patients with

monosensitization to P.j. pollen allergens; among them, 12 had started

SIT with a P.j. extract in autumn 1993. As a control group, 13 patients

were untreated. All patients were studied with various tests at four

different times: time I-November 1993; time II-February 1994; time

III-end of May 1994; and time IV-September 1994. Blood samples for

determination of serum ECP were collected at each time. Methacholine

challenge tests were performed at times I and III. A pollen count was

also carried out. A statistically significant difference (P < 0.05) was

observed in mean ECP levels at times I and III in SIT treated and

untreated patients. The interaction between groups and time was not

significant. No statistically significant difference was found between

PD20 FEV1 values at times I and III in either group. After 1 year of

treatment, we did not find any effect of SIT on bronchial

hyperresponsiveness or on ECP serum values.

Language of Publication

English

Unique Identifier

96385061

5. Grass pollen immunotherapy inhibits allergen-induced infiltration

of CD4+ T lymphocytes and eosinophils in the nasal mucosa and increases

the number of cells expressing messenger RNA for interferon-gamma.

Title Abreviation: J Allergy Clin

Immunol Date of Pub: 1996 Jun

Author: Durham SR; Ying S; Varney VA; Jacobson MR; Sudderick RM; Mackay

IS; Kay AB; Hamid QA;

Issue/Part/Supplement: 6 Volume Pagination: 1356-65

Issue: 97

MESH Headings: Adult*; Allergens*; Chemotaxis, Leukocyte*; Cytokines*;

CD4-Positive T-Lymphocytes*; Double-Blind Method*; Eosinophils*; Female;

Gene Expression*; Grasses*; Hay Fever*; Human; Immunotherapy*; Interferon

Type II*; Male; Nasal Mucosa*; Nasal Provocation Tests*; Pollen*; RNA,

Messenger*; Support, Non-U.S. Gov't; -PG-;

Journal Title Code: H53 Publication Type: CLINICAL TRIAL

Date of Entry: 960725N Entry Month: 9609

Country: UNITED STATES Index Priority: 1

Language: Eng Unique Identifier: 96243717

Unique Identifier:

96243717 ISSN: 0091-6749

Abstract: BACKGROUND: Grass pollen injection immunotherapy is effective in

patients with summer hay fever, although efficacy must be balanced against

possible side effects. The mechanism of immunotherapy is unknown but may

be related to its ability to inhibit allergen-induced late responses,

which are known to be characterized by infiltration of T lymphocytes,

eosinophils, and cells with messenger RNA for so-called TH2-type cytokines

(IL-4 and IL-5). OBJECTIVE: This study was designed to observe the effect

of grass pollen immunotherapy on late nasal responses and associated

cellular infiltration and cytokine mRNA expression. METHODS: We performed

local nasal provocation with grass pollen (and a control challenge) in 28

patients after a 12-month double-blind, placebo-controlled trial of

immunotherapy. Nasal biopsy specimens were obtained at 24 hours and

processed for immunohistology and in situ hybridization studies. RESULTS:

Grass pollen immunotherapy inhibited allergen-induced immediate (0 to 60

minutes) increases in sneezing (p < 0.02) and nasal blocking (p < 0.01)

and late (0 to 24 hours) nasal symptoms (p < 0.05). Immunotherapy also

inhibited the associated infiltration of the nasal mucosa by CD4+ T

lymphocytes and total (major basic protein-containing) and "activated"

(cationic protein-secreting) eosinophils (all p = 0.03). There was a

significant (p = 0.04) increase in cells expressing mRNA for

interferon-gamma at 24 hours after allergen challenge, which correlated

inversely with patients' seasonal symptoms (r = -0.65, p < 0.05) and

medication requirements (r = -0.75, p < 0.02) during the pollen season.

CONCLUSION: The results suggest that successful grass pollen immunotherapy

for summer hay fever may act by inhibiting allergen-induced T lymphocyte

and eosinophil recruitment and eosinophil activation in the target organ,

possibly through a mechanism involving protective local increases in

TH1-type cells.

Abstract By: Author

Address: Department of Allergy and Clinical Immunology, Royal Brompton

Hospital and National Heart & Lung Institute, Imperial College, London.

6. Serum level of interleukin-4 in patients with perennial allergic

rhinitis during allergen-specific immunotherapy.

Author

Ohashi_Y; Nakai_Y; Okamoto_H; Ohno_Y; Sakamoto_H; Sugiura_Y;

Kakinoki_Y; Tanaka_A; Kishimoto_K; Washio_Y; Hayashi_M

Address

Department of Otolaryngology, Osaka City University Medical School,

Japan.

Source

Scand J Immunol, 1996 Jun, 43:6, 680-6

Abstract

Interleukin-4 (IL-4) may play a central role in the IgE synthesis

system, the development of Th-2-like cells, and co-ordination as well

as the persistence of airway inflammatory process in allergic

disorders. Therefore, IL-4 plays a key role in airway allergic

disorders. This study aimed at investigating the serum concentrations

of IL-4 in patients with perennial allergic rhinitis, with special

reference to the possible changes and the clinical relevance following

long-term immunotherapy. The study has demonstrated that the serum

level of IL-4 in allergic rhinitis patients before immunotherapy is

significantly higher than that in non-atopic individuals. However, the

serum IL-4 level in allergic rhinitis patients did not decrease

following anti-allergic medications but significantly decreased

following immunotherapy. The percentage decrease in IL-4 was correlated

significantly with the percentage decrease in specific IgE antibodies

following long-term immunotherapy. Immunotherapy also significantly

decreased specific IgE anti-bodies, but this reduction in specific IgE

antibodies was not significantly correlated with the clinical

improvement. In contrast, the percentage decrease in serum IL-4 was

significantly correlated with the percentage decrease in symptomatic

scores. The authors interpret these data to mean that immunotherapy

alters T-cell cytokine profiles in the long-term, and a decline of IL-4

following immunotherapy could modulate not only production of specific

IgE antibodies but also inflammatory cellular events, leading to

symptomatic relief in allergic rhinitis.

Language of Publication

English

Unique Identifier

96257902

7. Immunologic effects of encapsulated short ragweed extract: a potent

new agent for oral immunotherapy.

Title Abreviation: Ann Allergy Asthma

Immunol Date of Pub: 1996 Aug

Author: Litwin A; Flanagan M; Entis G; Gottschlich G; Esch R; Gartside P;

Michael JG;

Issue/Part/Supplement: 2 Volume Issue: Pagination: 132-8

77

MESH Headings: Adult*; Allergens*; Antibodies, Anti-Idiotypic*;

Desensitization, Immunologic*; Dose-Response Relationship, Immunologic*;

Drug Compounding*; Enzyme-Linked Immunosorbent Assay*; Hay Fever*; Human;

IgA*; IgE*; IgG*; Kinetics*; Middle Age*; Nasal Mucosa*; Pollen*;

Radioallergosorbent Test*; Support, Non-U.S. Gov't; -PG-;

Journal Title Code: CBM Publication Type: JOURNAL ARTICLE

Date of Entry: 960920N Entry Month: 9611

Country: UNITED STATES Index Priority: 1

Language: Eng Unique Identifier: 96339290

Unique Identifier:

96339290 ISSN: 1081-1206

Abstract: BACKGROUND: Oral allergen immunotherapy with conventional

allergens has not been a useful mode of treatment because of the lack of

potency of allergens when administered by this route. OBJECTIVE: To study

the immunologic potency of short ragweed pollen extracts microencapsulated

by a new technique administered orally to short ragweed pollen-sensitive

humans and to establish the dose of oral microencapsulated short ragweed

pollen extract required for these effects. METHODS: Nine short ragweed

pollen-sensitive patients were treated with a new oral agent for

immunotherapy, microencapsulated short ragweed pollen extract, in an open

study. The effectiveness of this treatment was determined by comparison to

a group of nine matched short ragweed pollen-sensitive patients who

received no treatment. Treated patients developed high titers of short

ragweed-specific IgG and IgE antibodies and their expected seasonal

increase in IgE antibodies was regulated. The dose of microencapsulated

short ragweed pollen extract required to achieve these effects was only

slightly higher than the dose of short ragweed pollen extract used in high

dose subcutaneous immunotherapy. Furthermore, this dose was achieved in 7

weeks. There were no side effects other than mild gastrointestinal ones.

The nine treated patients fared clinically better during the ragweed

season than the untreated patients in this open study. CONCLUSION: This

study suggests that allergens microencapsulated by this new technique may

make oral immunotherapy a practical mode of treatment.

Abstract By: Author

Address: Department of Molecular Genetics, College of Medicine, University

of Cincinnati, Ohio, USA.

8. Immunotherapy suppresses the production of monocyte chemotactic and

activating factor and augments the production of IL-8 in children with

asthma.

Author

Hsieh_KH; Chou_CC; Chiang_BL

Address

Department of Pediatrics, National Taiwan University College of

Medicine, Taipei, Republic of China.

Source

J Allergy Clin Immunol, 1996 Sep, 98:3, 580-7

Abstract

BACKGROUND: Histamine-releasing factor consists of a group of cytokines

that can cause basophils or mast cells to release histamine. However,

the composition of histamine-releasing factor remains undefined.

OBJECTIVE: This study was done to measure the concentrations, in plasma

and mononuclear cell culture supernatants from children with asthma, of

chemokines that are known to contribute to histamine-releasing factor

activity. RESULTS: Plasma and mononuclear cell culture supernatants

were obtained from 25 children newly diagnosed with asthma, 25 good

responders to immunotherapy, 23 poor responders, 25 patients with acute

attacks, and 13 normal subjects. All the patient groups produced,

spontaneously and after stimulation with phytohemagglutinin and mite

allergen, greater amounts of monocyte chemotactic and activating

factor, macrophage inflammatory protein-1 alpha, and RANTES (beta

chemokines) and IL-8 and growth-related gene alpha (alpha chemokines)

than did normal subjects. Successful immunotherapy resulted in

decreased production, especially the spontaneous type, of beta

chemokines that cause histamine release and in increased production of

a chemokines that inhibit histamine release. CONCLUSION: Abnormal

chemokine production may contribute to the pathogenesis of bronchial

asthma, and restoration of normal chemokine production may be used to

explain, in part, the clinical efficacy of immunotherapy.

Language of Publication

English

Unique Identifier

96426242

9. Serum levels of soluble interleukin-2 receptor in patients with

perennial allergic rhinitis before and after immunotherapy.

Author

Ohashi_Y; Nakai_Y; Sakamoto_H; Ohno_Y; Sugiura_Y; Okamoto_H; Tanaka_A;

Kakinoki_Y; Kishimoto_K; Hayashi_M

Address

Department of Otolaryngology, Osaka City University Medical School,

Japan.

Source

Ann Allergy Asthma Immunol, 1996 Sep, 77:3, 203-8

Abstract

BACKGROUND: Interleukin-2 receptor (IL-2R) exists in soluble form in

sera, and the rate of release of the soluble form of IL-2R (soluble

IL-2R) reflects T cell activation in vivo. Since T lymphocytes play a

central role in respiratory allergic disorders, the measurement of

serum levels of soluble IL-2R may be useful in analyzing the disease

state of allergic disorders. OBJECTIVE: To investigate the serum

concentrations of soluble IL-2R in 48 patients with perennial allergic

rhinitis and 14 nonatopic healthy controls, with special reference to

the possible changes following long-term immunotherapy. METHODS: This

retrospective study included 48 patients who had had variable periods

of long-term immunotherapy with Dermatophagoides farinae extracts. The

duration of immunotherapy ranged from 5 to 15 years. Serum samples were

collected twice from each patient, before the initiation of

immunotherapy and at the time of clinical assessment of immunotherapy.

All the serum samples were simultaneously used for determination of

soluble IL-2R concentrations, by the use of an enzyme-linked

immunosorbent assay. To serve as controls, 14 nonallergic subjects of

the same age range and sex were chosen. RESULTS: Patients with allergic

rhinitis before immunotherapy had significantly higher serum levels of

soluble IL-2R than nonatopic subjects. Elevated serum levels of soluble

IL-2R decreased significantly following immunotherapy and the serum

levels of soluble IL-2R in patients with allergic rhinitis after

immunotherapy were not statistically different from those of nonatopic

subjects. In addition, the percent decrease in serum soluble IL-2R

correlated significantly with the duration of immunotherapy.

CONCLUSIONS: Hyperactivity of helper T cells of atopic patients is

altered after long-term immunotherapy, and such immunoregulatory

changes could be theoretically involved in the mechanisms of

immunotherapy.

Language of Publication

English

Unique Identifier

96409062

10. Serum levels of soluble interleukin-2 receptor in patients with

perennial allergic rhinitis before and after immunotherapy.

Author

Ohashi_Y; Nakai_Y; Sakamoto_H; Ohno_Y; Sugiura_Y; Okamoto_H; Tanaka_A;

Kakinoki_Y; Kishimoto_K; Hayashi_M

Address

Department of Otolaryngology, Osaka City University Medical School,

Japan.

Source

Ann Allergy Asthma Immunol, 1996 Sep, 77:3, 203-8

Abstract

BACKGROUND: Interleukin-2 receptor (IL-2R) exists in soluble form in

sera, and the rate of release of the soluble form of IL-2R (soluble

IL-2R) reflects T cell activation in vivo. Since T lymphocytes play a

central role in respiratory allergic disorders, the measurement of

serum levels of soluble IL-2R may be useful in analyzing the disease

state of allergic disorders. OBJECTIVE: To investigate the serum

concentrations of soluble IL-2R in 48 patients with perennial allergic

rhinitis and 14 nonatopic healthy controls, with special reference to

the possible changes following long-term immunotherapy. METHODS: This

retrospective study included 48 patients who had had variable periods

of long-term immunotherapy with Dermatophagoides farinae extracts. The

duration of immunotherapy ranged from 5 to 15 years. Serum samples were

collected twice from each patient, before the initiation of

immunotherapy and at the time of clinical assessment of immunotherapy.

All the serum samples were simultaneously used for determination of

soluble IL-2R concentrations, by the use of an enzyme-linked

immunosorbent assay. To serve as controls, 14 nonallergic subjects of

the same age range and sex were chosen. RESULTS: Patients with allergic

rhinitis before immunotherapy had significantly higher serum levels of

soluble IL-2R than nonatopic subjects. Elevated serum levels of soluble

IL-2R decreased significantly following immunotherapy and the serum

levels of soluble IL-2R in patients with allergic rhinitis after

immunotherapy were not statistically different from those of nonatopic

subjects. In addition, the percent decrease in serum soluble IL-2R

correlated significantly with the duration of immunotherapy.

CONCLUSIONS: Hyperactivity of helper T cells of atopic patients is

altered after long-term immunotherapy, and such immunoregulatory

changes could be theoretically involved in the mechanisms of

immunotherapy.

Language of Publication

English

Unique Identifier

96409062

11. Change of chemokines during immunotherapy in asthmatic children.

Author

Chiang_BL; Lu_FM; Chuang_YH; Chou_CC; Hsieh_KH

Address

Graduate Institute of Immunology, National Taiwan University College of

Medicine, Taipei, R.O.C.

Source

Acta Paediatr Sin, 1996 Sep-Oct, 37:5, 324-32

Abstract

Histamine-releasing factor (HRF) consists of a group of cytokines that

can cause basophil/mast cell to release histamine, however, the

composition of HRF still remains undefined. This study was designed to

measure the concentrations of chemokines in asthmatic children

receiving immunotherapy. Peripheral blood mononuclear cells culture

supernatants were obtained from six asthmatic children before and four,

eight months after immunotherapy (IT). The levels of monocyte

chemotactic and activating factor (MCAF), macrophage inflammatory

protein-1a (MIP-1a), regulated on activation normal T-cell expressed

and secreted (RANTES) and interleukin-8 (IL-8) spontaneously and after

stimulation with PHA and mite allergen in the supernatants. The data

showed: 1) The levels of MCAF and MIP-1a increased four months, and

decreased eight months, after IT; 2) By contrast, the level of RANTE

increased after IT; 3) The level of IL-8 also tended to increase after

IT. Abnormal chemokine production may contribute to the pathogenesis of

bronchial asthma and restoration of normal chemokine production may be

used to partially explain the clinical efficacy of immunotherapy.

Language of Publication

English

Unique Identifier

97097402

12. Decrease in CD23+ B lymphocytes and clinical outcome in asthmatic

patients receiving specific rush immunotherapy.

Author

Kljaic-Turkalj_M; Cvoriscec_B; Tudoric_N; Stipic-Markovic_A; Rabatic_S;

Trescec_A; Gagro_A; Dekaris_D

Address

Department of Pulmonary Diseases and Clinical Immunology, General

Hospital, Sveti Duh, Zagreb, Croatia.

Source

Int Arch Allergy Immunol, 1996 Oct, 111:2, 188-94

Abstract

Rush immunotherapy (RIT) has been documented as useful in the treatment

of patients with allergic bronchial asthma. To investigate the

mechanisms of its action, we studied changes in the serum levels of

total IgE, allergen-specific IgE and IgG4, and expression of CD23 on

peripheral blood B cells in patients receiving RIT. Twenty patients

with perennial bronchial asthma were evaluated before the beginning of

RIT, as well as 6 weeks and 6 months later. Compared to pretreatment

values, the level of Der-p-specific IgG4 and IgE significantly

increased after 6 weeks and 6 months of RIT, while the total serum IgE

remained unchanged. Furthermore, after 6 months of RIT, the percentage

of CD23+B cells and its CD23 receptor density significantly decreased.

Since the symptom score improved and the need for medication decreased,

we evaluated RIT as a useful procedure. After 6 months, 30% of patients

did not have an asthma attack, with no medication in the last month,

while 10% of them were asthma free for the last 3 months. No

significant correlation between the clinical improvement, and in vitro

changes was found. Furthermore, the observed in vitro changes were not

significantly different in patients who responded with clinical

improvement, compared to those with unchanged intensity of asthma. In

conclusion, during specific RIT we found a significant increase in

Der-p-specific IgE and IgG4 antibodies, as well as a moderate decrease

in CD23+ B cells and its CD23 receptor density. These findings suggest

a change in the lymphokine profile of patients receiving specific

immunotherapy, and that the inhibition of IL-4-induced B cell

stimulation may be hypothesized as the most important mechanism.

Language of Publication

English

Unique Identifier

97012414

13. Mediator release is altered in immunotherapy-treated patients: a 4-year

study.

Author

Dokic_D; Nethe_A; Kleine-Tebbe_J; Kunkel_G; Baumgarten_CR

Address

Department of Clinical Immunology and Asthma, Universitätsklinikum

Rudolf Virchow, Berlin, Germany.

Source

Allergy, 1996 Nov, 51:11, 796-803

Abstract

In recent years, it has been possible to demonstrate mediator release

into the nasal secretion after nasal allergen challenge in patients

with allergic rhinitis. Using the nasal provocation model, we

determined whether the mediator release was altered in

immunotherapy-treated patients. Seventeen grass-pollen-allergic

patients were examined under controlled, reproducible conditions.

Serial challenges with increasing doses of grass pollen produced

increasing numbers of clinical symptoms and release of mediators such

as kinins, TAME-esterase activity, and histamine. Ten patients received

a semidepot perennial grass-pollen extract for 4 years. Seven patients

served as controls and did not receive immunotherapy during the

observation period. Data from the group of patients receiving

immunotherapy over the first year already showed a partially

significant decline in the maximal mediator release after nasal

allergen challenges compared to the results of pretreated challenges,

whereas controls did not show any significant changes. Nasal allergen

challenges after termination of 4 years' immunotherapy significantly

modified the mediator release compared to pretreatment values

(TAME-esterase activity P < 0.05, kinins P < 0.01, and histamine P <

0.01). Decrease of mediator release paralleled the symptom-medication

scores and quantitative skin prick test. Finally, we could demonstrate

a significant correlation between specific IgG increase and mediator

decrease in the treated group.

Language of Publication

English

Unique Identifier

97102965

14. Measurement of IgE antibodies against purified grass pollen allergens

(Lol p 1, 2, 3 and 5) during immunotherapy.

Author

Van_Ree_R; Van_Leeuwen_WA; Dieges_PH; Van_Wijk_RG; De_Jong_N;

Brewczyski_PZ; Kroon_AM; Schilte_PP; Tan_KY; Simon-Licht_IF; Roberts;

AM; Stapel_SO; Aalberse_RC

Address

Central Laboratory of The Netherlands Red Cross Blood Transfusion

Service, Amsterdam, The Netherlands.

Source

Clin Exp Allergy, 1997 Jan, 27:1, 68-74

Abstract

BACKGROUND: IgE titres tend to rise early after the start of

immunotherapy, followed by a decline to pre-immunotherapy levels or

lower. OBJECTIVES: We were interested to know whether the early

increase in IgE antibodies includes new specificities of IgE, and

whether these responses persist. METHODS: Sera of 64 patients

undergoing grass pollen immunotherapy were tested for IgE against four

purified grass pollen allergens: Lol p 1, 2, 3, and 5. At least two

serum samples were taken, one before the start of therapy and one

between 5 and 18 months after the first immunization (mean: 10 months).

RESULTS: The mean IgE responses to Lol p 1, 2 and 3 showed a moderate

but not significant increase. In contrast, the mean IgE response to Lol

p 5 showed a significant decrease of > 30%. IgE against total Lohum

perenne pollen extract moderately increased (> 20%), showing that a

RAST for total pollen is not always indicative for the development of

IgE against its major allergens. For > 40% of the patients it was found

that IgE against one or more of the four allergens increased, while IgE

against the remaining allergen(s) decreased. For 10 sera the ratio of

IgE titres against at least two allergens changed by at least a factor

of 5. The changes in specific IgE also included conversions from

negative (< 0.1 RU) to positive (0.6 to 5.0 RU) for five patients. For

two patients, the induction of these 'new' IgE antibodies against major

allergens was shown to result in a response that was persistent over

several years. CONCLUSION: Although active induction of new IgE

specificities by immunotherapy was not really proven, the observations

in this study indicate that monitoring of IgE against purified (major)

allergens is necessary to evaluate changes in specific IgE in a

reliable way.

Language of Publication

English

Unique Identifier

97196702

15. House dust mite immunotherapy results in a decrease in Der p 2-specific

IFN-gamma and IL-4 expression by circulating T lymphocytes.

Author

O'Brien_RM; Byron_KA; Varigos_GA; Thomas_WR

Address

University of Melbourne Department of Medicine, Western Hospital,

Footscray, Australia.

Source

Clin Exp Allergy, 1997 Jan, 27:1, 46-51

Abstract

BACKGROUND: Allergen-specific immunotherapy (IT) can be an important

adjunctive therapy in the treatment of allergic disorders. Although it

has now been used for over 80 yr, the precise mechanism of action

remains unclear. Recently a number of studies have shown that cytokine

production may be modified by IT, but different protocols have been

used and different results obtained. OBJECTIVES: The aims of the

present study were: (1) to document the allergen-specific expression of

interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) by peripheral

blood cells in both untreated house dust mite (HDM) allergic patients

(non-IT) and following at least 10 months of HDM-specific IT (post-IT);

and (2) to determine whether alterations in these critical regulatory

cytokines correlated with the clinical outcome of IT. METHODS: IT was

undertaken with nine fortnightly subcutaneous injections of increasing

amounts of a Dermatophagoides pteronyssinus (Dpt) extract, reaching a

final dose of 10,000 PNU. This was followed by 6- to 8-monthly

maintenance injections of 5000 PNU. For cytokine measurement,

mononuclear cells were separated from peripheral blood and stimulated

with the major Dpt allergen, Der p 2, for 18 h, after which mRNA was

isolated and IL-4 and IFN-gamma cDNA were amplified by polymerase chain

reaction (PCR). The presence of the particular cytokine was determined

by visualization following electrophoresis on an agarose gel. The study

was observational in nature being open and without a placebo group.

RESULTS: Fifteen Dpt-sensitive patients who had not received HDM IT

(non-IT), and 16 who had, were studied. In the non-IT group, 80%

expressed IL-4 and 75% expressed IFN-gamma. In those post-IT, only

12.5% expressed IL-4 and 19% IFN-gamma. The two patients still

expressing IL-4 post-IT had had very little clinical response. Six

patients were studied both pre- and post-IT. Prior to IT, three were

positive for both cytokines, two positive for IL-4 alone and one for

IFN-gamma. Post-IT, all six were negative for IL-4 and five were

negative for IFN-gamma. CONCLUSION: Allergen-specific IT results in a

reduction in expression of the critical cytokines IL-4 and IFN-gamma in

circulating lymphocytes. It is possible that this is a contributary

mechanism in the beneficial effect of IT.

Language of Publication

English

Unique Identifier

97196699

16. Increases in IL-12 messenger RNA+ cells accompany inhibition of

allergen-induced late skin responses after successful grass pollen

immunotherapy [see comments]

Author

Hamid_QA; Schotman_E; Jacobson_MR; Walker_SM; Durham_SR

Address

Department of Medicine and Pathology, Meakins Christie Laboratory,

McGill University, Montreal, Canada.

Source

J Allergy Clin Immunol, 1997 Feb, 99:2, 254-60

Abstract

IL-12, a novel cytokine produced by tissue macrophages and B

lymphocytes, stimulates proliferation of TH1-type T lymphocytes. We

recently showed that in patients with summer hay fever, immunotherapy

was effective and was associated with inhibition of allergen-induced

late skin responses and increases in local interferon-gamma messenger

RNA-positive cells. In this study 10 patients were reassessed after 4

years of immunotherapy and compared with 10 untreated patients with hay

fever. Intradermal grass pollen challenge was performed, the late

response was measured, and biopsies were performed at 24 hours. In situ

hybridization of biopsy sections was performed by using a riboprobe

coding for IL-12 mRNA. When immunotherapy and control subjects were

compared, there was a marked reduction in the size of the late skin

response (p = 0.0001). Significant increases in allergen-induced IL-12

mRNA+ cells in cutaneous biopsy specimens occurred only in the

immunotherapy-treated group (all 10 patients, p = 0.002). At

allergen-challenged sites, IL-12+ cells correlated positively with

interferon-gamma + cells (r = 0.64, p < 0.05) and inversely with IL-4+

cells (r = -0.67, p < 0.05). The principal cell source (55% to 80%) of

IL-12 message was the tissue macrophage (CD68+ cells). We suggest that

IL-12 may promote TH1 responses and inhibit late-phase responses after

successful immunotherapy.

Language of Publication

English

Unique Identifier

97194617

17. Natural course of serum-specific immunoglobulin E and immunoglobulin G4

for a span of eight years in untreated patients with perennial allergic

rhinitis.

Author

Ohashi_Y; Nakai_Y; Ohno_Y; Okamoto_H; Kakinoki_Y; Masamoto_T; Tanaka_A;

Hayashi_M

Address

Department of Otolaryngology, Osaka City University Medical School,

Osaka, Japan.

Source

Laryngoscope, 1997 Mar, 107:3, 382-5

Abstract

During the past two decades, considerable attention has been devoted to

the clinical role of serum-specific IgE and IgG4 following

immunotherapy. To definitely discuss the clinical role of

serum-specific IgG4, we should know the natural course of

serum-specific IgG4 in the untreated patient with allergic rhinitis. To

our knowledge, however, no such kind of study can be found in the

literature. Our present study focused on the long-term follow-up of

serum-specific IgE and IgG4 in patients who were not treated with

immunotherapy for perennial allergic rhinitis. They were scheduled to

take no medication for their perennial nasal symptoms for 8 years.

Serum-specific IgE and IgG4 in untreated patients with perennial

allergic rhinitis never significantly change during the observation

period. These data will be of great value for studies in serologic

changes following active treatment for atopic diseases. Additionally,

our study suggests that a reduction in serum-specific IgE and an

increase in serum-specific IgG4 following immunotherapy are not the

result of an immunotherapy-independent and age-related phenomenon but

the result of active immunologic modulation by immunotherapy.

Language of Publication

English

Unique Identifier

97238532

1. Fel d 1 peptides: effect on skin tests and cytokine synthesis in

cat-allergic human subjects.

Author

Simons_FE; Imada_M; Li_Y; Watson_WT; HayGlass_KT

Address

Health Sciences Clinical Research Centre, Faculty of Medicine,

University of Manitoba, Canada.

Source

Int Immunol, 1996 Dec, 8:12, 1937-45

Abstract

We tested peptide immunotherapy in cat-allergic humans, using a

formation of two synthetic peptides, IPC-1 and IPC-2, each of which is

27 amino acids long and contains T cell-reactive regions of Fel d 1,

the major cat allergen. In this exploratory, randomized, double-blind,

parallel-group study, 42 subjects received s.c. injections of treatment

peptides 250 micrograms or placebo weekly for four consecutive weeks.

Changes in immediate- and late-phase skin test reactivity, and in

antigen-driven cytokine synthesis were assessed. Epicutaneous

(end-point titration) and intradermal tests were performed with cat

extract (ALK SQ Cat Hair) containing Fel d 1, before the first

injection, then 2, 6 and 24 weeks after the fourth and last injection

of peptides or placebo. IL-4, IL-10 and IFN-gamma expression by

circulating peripheral blood mononuclear cells (PBMC) in response to

cat extract was measured using short-term bulk culture of PBMC and

short-term limiting dilution analysis. Subjects who received peptide

immunotherapy did not tolerate significantly more cat extract

containing Fel d 1 in the skin tests 2, 6 or 24 weeks after the last

injection than they did at baseline, and their late-phase responses did

not decrease significantly compared to baseline. Substantial IL-4,

IL-10 and IFN-gamma responses were observed following primary culture

of cat antigen-stimulated PBMC; however, the intensity of cytokine

synthesis and the IFN-gamma: IL-4 ratio were unchanged in peptide- and

placebo-treated groups 6 and 24 weeks after the last injection. A few

hours after the injections, subjects receiving peptides reported more

allergic rhinitis and asthma symptoms and more pruritus than those

receiving placebo. We conclude that under the conditions tested,

peptide immunotherapy did not reduce immediate- or late-phase skin

reactivity to cat extract containing Fel d 1 or modify cat

antigen-specific cytokine production significantly.

Language of Publication

English

Unique Identifier

97137441

2. From epitopes to peptides to immunotherapy.

Author

Hoyne_G; Bourne_T; Kristensen_N; Hetzel_C; Lamb_J

Address

Department of Biology, Imperial College of Science, Technology and

Medicine, London, United Kingdom.

Source

Clin Immunol Immunopathol, 1996 Sep, 80:3 Pt 2, S23-30

Abstract

Allergic inflammatory responses are regulated by cytokines [interleukin

(IL)-4, IL-5, IL-10, and IL-13] produced by CD4+ helper (Th0 and Th2)

cells. The activation of these T cells follows engagement of T-cell

antigen receptors (TCR) by antigenic peptides complexed with major

histocompatibility complex (MHC) class II molecules. Under defined

conditions presentation of T-cell epitopes as peptides can downregulate

immune responses, and here we discuss the potential of peptide-mediated

immunotherapy in the regulation of responses to the house dust mite

(HDM). Cloning the major allergens of HDM has allowed detailed analysis

of the HDM-reactive T-cell repertoire and has revealed that MHC class

II restriction is heterogeneous, involving HLA-DP,-DQ, and -DR

molecules, and that multiple T-cell epitopes are recognized. There is,

however, evidence for a bias in TCR gene usage, which has prompted the

analysis of peptide-mediated densitization of human T cells in vitro.

CD4+ T cells exposed to high concentrations of HDM peptides become

refractory to restimulation and fail to provide B-cell help. This is

accompanied by complex changes in the surface phenotype, including the

downregulation of TCR and CD28. During the induction of anergy

cytokine-specific mRNA levels are enhanced, but when the anergic T

cells are restimulated they fail to secrete IL-4 and IL-5, although

interferon (IFN)-gamma production may remain unaltered. The ability of

peptides to modulate the function of HDM-specific T cells in vivo has

been investigated in mice. Following inhalation of peptide containing a

major T-cell epitope of Der p 1 (residues 111-139) transient T-cell

activation was observed prior to the inhibition of responses in naive

and sensitized mice. T cells from the tolerant mice restimulated in

vitro produced low levels of cytokines and failed to provide help for B

cells.

Language of Publication

English

Unique Identifier

96406973

3. Peptide-mediated regulation of the allergic immune response.

Author

Hoyne_GF; Lamb_JR

Address

Department of Biology, Imperial College of Science, Technology and

Medicine, London, United Kingdom.

Source

Immunol Cell Biol, 1996 Apr, 74:2, 180-6

Abstract

A major key to successful immunotherapy may depend on altering the

qualitative nature of the immune response in allergic patients. In this

review we examine how immune responses to environmental allergens are

regulated, and the mechanisms used by the immune system to prevent

allergic sensitization. We also discuss future prospects of using

allergen-derived peptides in immunotherapy and the possibility of

'reprogramming' the immune responses by immunizing under conditions

that promote Th1 responses instead of Th2 responses.

Language of Publication

English

Unique Identifier

96315695

4. Dissection of immunoglobulin E and T lymphocyte reactivity of isoforms

of the major birch pollen allergen Bet v 1: potential use of

hypoallergenic isoforms for immunotherapy.

Author

Ferreira_F; Hirtenlehner_K; Jilek_A; Godnik-Cvar_J; Breiteneder_H;

Grimm_R; Hoffmann-Sommergruber_K; Scheiner_O; Kraft_D; Breitenbach; M;

Rheinberger_HJ; Ebner_C

Address

Institut für Genetik und Allg. Biologie, Universität Salzburg, Austria.

Source

J Exp Med, 1996 Feb 1, 183:2, 599-609

Abstract

We dissected the T cell activation potency and the immunoglobulin (Ig)

E-binding properties (allergenicity) of nine isoforms of Bet v 1 (Bet v

1a-Bet v 1l), the major birch pollen allergen. Immunoblot experiments

showed that Bet v 1 isoforms differ in their ability to bind IgE from

birch pollen-allergic patients. All patients tested displayed similar

IgE-binding patterns toward each particular isoform. Based on these

experiments, we grouped Bet v 1 isoforms in three classes: molecules

with high IgE-binding activity (isoforms a, e, and j), intermediate

IgE-binding (isoforms b, c, and f), and low/no IgE-binding activity

(isoforms d, g, and 1). Bet v 1a, a recombinant isoform selected from a

cDNA expression library using IgE immunoscreening exhibited the highest

IgE-binding activity. Isoforms a, b, d, e, and 1 were chosen as

representatives from the three classes for experimentation. The potency

of each isoallergen to activate T lymphocytes from birch

pollen-allergic patients was assayed using peripheral blood mononuclear

cells, allergen-specific T cell lines, and peptide-mapped

allergen-specific T cell clones. Among the patients, some displayed a

broad range of T cell-recognition patterns for Bet v 1 isoforms whereas

others seemed to be restricted to particular isoforms. In spite of this

variability, the highest scores for T cell proliferative responses were

observed with isoform d (low IgE binder), followed by b, 1, e, and a.

In vivo (skin prick) tests showed that the potency of isoforms d and 1

to induce typical urticarial type 1 reactions in Bet v 1-allergic

individuals was significantly lower than for isoforms a, b, and e.

Taken together, our results indicate that hypoallergenic Bet v 1

isoforms are potent activators of allergen-specific T lymphocytes, and

Bet v 1 isoforms with high in vitro IgE-binding activity and in vivo

allergenicity can display low T cell antigenicity. Based on these

findings, we propose a novel approach for immunotherapy of type I

allergies: a treatment with high doses of hypoallergenic isoforms or

recombinant variants of atopic allergens. We proceed on the assumption

that this measure would modulate the quality of the T helper cell

response to allergens in vivo. The therapy form would additionally

implicate a reduced risk of anaphylactic side effects.

Language of Publication

English

Unique Identifier

96195212

5. Modulation of the human IgE response.

Author

de_Vries_JE; Yssel_H

Address

Human Immunology Dept, DNAX Research Institute for Molecular and

Cellular Biology, Palo Alto, CA, USA.

Source

Eur Respir J Suppl, 1996 Aug, 22:, 58s-62s

Abstract

Studies on the immunological basis of allergic diseases have indicated

that enhanced production of the cytokines interleukin (IL)-4 and IL-13

and the reduced production of interferon-gamma (IFN-gamma) by

allergen-specific T-cells contribute to enhanced immunoglobulin E (IgE)

synthesis and the development of allergic disease in certain

individuals. Therefore, inhibition of IL-4 and IL-13 synthesis or

blocking of activities of these cytokines would be one approach to

inhibiting IgE production. In the present communication, novel

approaches toward this goal are discussed. It is shown that an IL-4

mutant protein, in which the tyrosine residue at position 124 is

replaced by aspartic acid (IL-4,Y124D), binds with high affinity to the

IL-4 receptor, without receptor activation. IL-4,Y124D acts as a potent

antagonist both of IL-4 and IL-13 activity in vitro, and inhibits

immunoglobulin G4 (IgG4) and IgE production induced by these cytokines.

These data are compatible with the notion that the IL-4 and IL-13

receptors are complex receptors, which share a common component, which

is required for signal transduction. In addition, it has been

demonstrated that allergen-specific T-cells, belonging to the T-helper

2 (Th2) subset can be rendered anergic after incubation with

allergen-derived peptides representing minimal T-cell activation

inducing epitopes. These anergic Th2 cells failed to produce IL-4 and

IL-13, and failed to proliferate after activation with allergen and

antigen-presenting cells (APC). The anergized T cells also failed to

give B-cells help in IgE synthesis, although they expressed normal

levels of the CD40 ligand (CD40L). Exogenous IL-4 and IL-13 failed to

restore IgE synthesis, indicating that in addition to CD40L other

co-stimulatory signals are required for productive T-cell/B-cell

interactions, resulting in IgE synthesis. IgE production was restored

by exogenous IL-2, demonstrating that IL-2 reverses the nonresponsive

state and helper function of these nonresponsive T-cells. It is

tempting to speculate that induction of T-cell nonresponsiveness by

allergen-derived peptides may represent the underlying mechanisms for

successful immunotherapy in allergenic patients.

Language of Publication

English

Unique Identifier

97024821

6. Conversion of the major birch pollen allergen, Bet v 1, into two

nonanaphylactic T cell epitope-containing fragments: candidates for a

novel form of specific immunotherapy.

Author

Vrtala_S; Hirtenlehner_K; Vangelista_L; Pastore_A; Eichler_HG;

Sperr_WR; Valent_P; Ebner_C; Kraft_D; Valenta_R

Address

Department of Immunopathology, Institute of General and Experimental

Pathology, AKH, University of Vienna, Austria.

Source

J Clin Invest, 1997 Apr 1, 99:7, 1673-81

Abstract

A novel approach to reduce the anaphylactic activity of allergens is

suggested. The strategy makes use of the presence of conformational

immunoglobulin E (IgE) epitopes on one of the most common allergens.

The three dimensional structure of the major birch pollen allergen, Bet

v 1, was disrupted by expressing two parts of the Bet v 1 cDNA

representing amino acids 1-74 and 75-160 in Escherichia coli. In

contrast to the complete recombinant Bet v 1, the fragments showed

almost no allergenicity and exhibited random coil conformation as

analyzed by circular dichroism. Both nonanaphylactic fragments induced

proliferation of human Bet v 1-specific T cell clones, indicating that

they harbored all dominant T cell epitopes and therefore may be

considered as a basis for the development of a safe and specific T cell

immunotherapy.

Language of Publication

English

Unique Identifier

97248280

1. Rush immunotherapy: experience with a one-day schedule.

Title Abreviation: Ann Allergy Asthma

Immunol Date of Pub: 1996 Feb

Author: Sharkey P; Portnoy J;

Issue/Part/Supplement: 2 Volume Issue: Pagination: 175-80

76

MESH Headings: Adolescence; Allergens (*AE); Asthma (CO/TH); Child; Child,

Preschool; Desensitization, Immunologic (*AE/*MT); Drug Administration

Schedule; Female; Hay Fever (CO/TH); Human; Male; Support, Non-U.S. Gov't;

Time Factors; -RN-;

Journal Title Code: CBM Publication Type: JOURNAL ARTICLE

Date of Entry: 960412N Entry Month: 9606

Country: UNITED STATES Index Priority: 1

Language: Eng Unique Identifier: 96173283

Unique Identifier: 96173283 ISSN: 1081-1206

Abstract: INTRODUCTION: Rush immunotherapy is a method for rapidly

desensitizing patients to inhalant allergens. The frequency of systemic

reactions during rush immunotherapy is similar to conventional

immunotherapy when premedication is used. The most rapid protocol for rush

immunotherapy reported to date requires one and one-half days which is

inconvenient to patients and clinic schedules. To improve this situation

and decrease the cost of giving rush immunotherapy, we have developed a

1-day protocol. METHODS: for this ongoing study, 22 allergic patients

received rush immunotherapy consisting of eight injections over six hours

followed by two hours of observation in an outpatient clinic. Five had

rhinitis and the rest has asthma, seven of whom were steroid-dependent.

All were premedicated with astemizole, ranitidine, and prednisone for

three days including the day of rush immunotherapy, and peak expiratory

low rates were monitored. RESULTS: Systemic reactions were seen in five of

22 (23%). They occurred following the sixth injection (1), seventh

injection (2), or the final one (2) and consisted primarily of rhinitis or

pulmonary symptoms with one episode of mild anaphylaxis. A systemic

reaction was seen in only one steroid-dependent asthmatic patient. A local

reaction preceded a systemic reaction in only one patient. All but three

reached a maintenance dose in one day. All systemic reactions responded to

epinephrine and all patients could go home after rush immunotherapy. Only

one patient had a systemic reaction during the three months after rush

immunotherapy. CONCLUSION: One day rush immunotherapy is tolerated by most

patients with a systemic reaction rate comparable to conventional

immunotherapy. All patients were able to reach a maintenance dose months

sooner than weekly schedules. With refinement of this procedure, rush

immunotherapy may become a widely used method for desensitizing patients

with inhalant allergens, and could make immunotherapy less expensive and

more convenient.

Abstract By: Author

Address: Section of Allergy/Asthma/Immunology, The Children's Mercy

Hospital, Kansas City, Missouri, USA.

---

2.Rush immunotherapy with house dust extract in patients with mild

extrinsic asthma.

Title Abreviation: Tohoku J Exp Med Date of Pub: 1996 Apr

Author: Hirokawa Y; Kondo T; Kobayashi I; Ohta Y;

Issue/Part/Supplement: 4 Volume Issue: Pagination: 371-80

178

MESH Headings: Adolescence; Adult; Allergens (*AD/*TU); Anti-Asthmatic

Agents (AD/TU); Asthma (PP/*TH); Bronchi (PP); Bronchial Provocation

Tests; Bronchoconstriction (PH); Cromolyn Sodium (AD/TU); Dust (*AE);

Eosinophils; Female; Histamine (BL); Human; IgG (IM); Immunotherapy (*);

Leukocyte Count; Male; Middle Age; Radioallergosorbent Test; Respiratory

Function Tests; -RN-;

Journal Title Code: VTF Publication Type: CLINICAL TRIAL

Date of Entry: 961204N Entry Month: 9702

Country: JAPAN Index Priority: 2

Language: Eng Unique Identifier: 96397049

Unique Identifier: 96397049 ISSN: 0040-8727

Abstract: Rush immunotherapy (RIT) with house dust extract was given to 15

patients with mild extrinsic or mixed asthma. Every patient was strongly

positive for IgE on the radioimmunosorbent test and sensitive to house

dust extract on the scratch skin test. Nine patients were positive on the

bronchial provocation test to house dust extract and 6 could not be

examined. All patients did not drop out and got to house dust extract

solution 10(-1) within 1 week. The symptom-medication scores decreased

significantly after RIT. During RIT 1 patient developed a mild asthmatic

attack and 3 patients developed generalized skin reaction. Eight weeks

later, the threshold for house dust-provoked bronchoconstriction increased

in 9 patients, but did not in 3 patients. The blood eosinophil count and

blood histamine level significantly decreased. We conclude that RIT is

able to raise antigen concentrations for a short periods and effective but

not risky for mild asthma.

Abstract By: Author

Address: Department of Pulmonology, Tokai University School of Medicine,

Isehara, Japan.

3. A double-blind, placebo-controlled study of immunotherapy with

grass-pollen extract Alutard SQ during a 3-year period with initial

rush immunotherapy.

Author

Dolz_I; Martínez-Cócera_C; Bartolomé_JM; Cimarra_M

Address

San Carlos University Hospital, Department of Allergy, Madrid, Spain.

Source

Allergy, 1996 Jul, 51:7, 489-500

Abstract

Thirty patients with asthma and/or monosensitized allergic rhinitis

caused by grass pollen whose ages ranged from 15 to 35 years were

selected. Two groups were established at random: an active group and a

placebo group, and a double-blind study was done on treatment with

immunotherapy for a period of 3 continuous years, with initiation doses

administered according to the rush immunotherapy technique.

Grass-pollen allergen extract Alutard SQ and histamine as a placebo

were used. The objective parameters of efficacy evaluated were

end-point cutaneous tests, conjunctival provocation, bronchial

provocation, and symptom/medication scores, as well as specific

immunoglobulin determinations. The statistical evaluation of the

results was significant for the differences existing between the

initial and final time of the active group, and there were significant

differences between the two groups for all of the parameters

considered. We found no relationship between clinical improvement and

the range of specific immunoglobulin E values. Regarding the safety of

the treatment, systemic adverse effects were manifested only in the

initial phase (rush immunotherapy), and were easily controlled by

treatment. We conclude that the efficacy and safety of immunotherapy

with grass pollen make it possible to consider this treatment

fundamental in these patients.

Language of Publication

English

Unique Identifier

97017325

4. Rush Immunotherapy Results In Allergen-Specific Changes In T

Cells -- Study

DENVER, April 21, 1997 -- Rush immunotherapy targeting a single allergen makes distinct changes in T cells and stops allergic reactions, National Jewish Medical and Research Center physicians found, according to the April issue of the Journal of Allergy and Clinical Immunology.

"This study showed for the first time the T cell reaction to Immunotherapy is specific," said Erwin Gelfand, M.D., head of the Department of Pediatrics at National Jewish and principal investigator of the study. "If you give too many antigens in desensitization, the immune system may not be able to distinguish between them. But attacking one trigger or a few triggers at a time can prevent the allergic reaction."

Rush immunotherapy consists of a number of injections given over a short time to desensitize a person to certain allergens, such as dust mites, cat dander or different types of plants.

Ten boys and girls, allergic to house dust mites and cat dander, were given rush immunotherapy for house dust mites only. When treatment ended, the children were desensitized to dust mites but not to cat dander, which showed that T cells can respond selectively to rush immunotherapy. In rush immunotherapy, T cells produce more interferon gamma, an element that lowers allergic responses, and shut off production of pro-allergic cytokines, which can cause wheezing, runny nose, sneezing and watery eyes.

"After rush immunotherapy you are more tolerant to an allergen you would have reacted to without desensitization," Dr. Gelfand said.

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1. Discontinuing venom immunotherapy: outcome after five years.

Title Abreviation: J Allergy Clin Immunol Date of Pub: 1996 Feb

Author: Golden DB; Kwiterovich KA; Kagey-Sobotka A; Valentine MD;

Lichtenstein LM;

Issue/Part/Supplement: 2 Volume Issue: Pagination: 579-87

97

MESH Headings: Anaphylaxis*; Animal; Antibodies, Anti-Idiotypic*; Antibody

Specificity*; Arthropod Venoms*; Human; Hymenoptera*; Hypersensitivity*;

IgE*; Immunotherapy*; Skin Tests*; Support, Non-U.S. Gov't; Support, U.S.

Gov't, P.H.S.; Time Factors*; Treatment Outcome*; -PG-;

Journal Title Code: H53 Publication Type: JOURNAL ARTICLE

Date of Entry: 960618N Entry Month: 9608

Country: UNITED STATES Index Priority: 1

Language: Eng Unique Identifier: 96191238

Unique Identifier: 96191238 ISSN: 0091-6749

Abstract: BACKGROUND: The clinical and immunologic consequences of

discontinuing venom immunotherapy are not well-defined. To determine which

patients can safely stop treatment, we accepted all volunteers who had

completed at least 5 years of maintenance venom immunotherapy regardless

of the severity of the historical sting reaction, the persistence of venom

skin test sensitivity, or any other variable. METHODS: Sting challenge was

performed every 1 to 2 years after therapy was stopped; and venom-specific

skin tests were performed, and IgE antibody levels were measured. RESULTS:

Systemic symptoms occurred after challenge in eight of 270 stings (3%), in

seven of 74 patients (10%); only two reactions were clinically

significant. Venom skin test results became negative in 28% after 5 years

of venom immunotherapy (at the time of discontinuation) and were negative

in 56% to 67% of patients after 2 to 4 years without venom immunotherapy.

There was a parallel decrease in the venom-specific IgE antibody levels.

Challenge stings did not prevent the progressive decline in sensitivity,

nor did they increase the risk of sting reaction even after two sequential

stings 1 month apart. CONCLUSIONS: Venom immunotherapy can be safely

discontinued after 5 years of maintenance therapy in virtually all

patients, with the possible exception of those in whom the level of venom

sensitivity has not declined during therapy. Venom sensitivity decreases

with time even after venom therapy is stopped. Insect stings do not cause

re-sensitization, and there was no increased risk from sequential stings.

There appears to be a late-onset, non-IgG-mediated mechanism for long-term

suppression of allergic sensitivity by prolonged high-dose venom

immunotherapy.

Abstract By: Author

Address: Johns Hopkins University, Asthma and Allergy Center, Baltimore,

MD 21224-6821, USA.

2. Honeybee venom allergy: immunoblot studies in allergic patients after

immunotherapy and before sting challenge.

Author

Jeep_S; Paul_M; Müller_U; Kunkel_G

Address

Department of Dermatology, Clinical Immunology, and Asthma,

Universitätsklinikum Rudolf Virchow, Berlin, Germany.

Source

Allergy, 1996 Aug, 51:8, 540-6

Abstract

By immunoblot techniques, detailed antibody studies were performed with

sera of 20 honeybee-venom-allergic patients during or at the end of

specific immunotherapy (median duration: 3 years) and before honeybee

sting challenge. Before immunotherapy, all patients had experienced

systemic allergic reactions to a honeybee sting, with a mean severity

of 3.5 +/- 0.5 according to the Müller classification. After the sting

challenge, 10 patients (reactors) reacted again with a systemic

allergic reaction, whereas 10 patients (nonreactors) did not. No

differences were observed between reactors and nonreactors in total

serum IgE and specific IgE to honeybee venom at the time of challenge.

For immunoblot, honeybee venom (RELESS) was separated on 7.5-20%

SDS-PAGE. For detection of specific IgE, IgG, IgG1, IgG4, and IgM, an

alkaline phosphatase-linked second antibody was used. Both groups

showed 11 antibody-binding bands: at 52, 46, 40, 31, 18.7, 16.9, 13,

11, 10, 9, and 8 kDa; however, the antibody-binding pattern was

individual. The reactors differed from nonreactors in showing intense

IgE and less IgG4 binding to at least one single component of the venom

extract. For nonreactors, the inverse relationship was observed. The

hypothesis, "intensity of IgE > or = IgG4 leads to allergic symptoms",

was highly significant (P = 0.00026; chi-square). These immunoblot

findings could offer predictive value in distinguishing reactors from

nonreactors.

Language of Publication

English

Unique Identifier

97028644

3. CD28 expression is increased in venom allergic patients but is not

modified by specific immunotherapy [see comments]

Author

Tsicopoulos_A; Labalette_M; Akoum_H; Duez_C; Wallaert_B; Dessaint_JP;

Tonnel_AB

Address

Unité INSERM U416, Institut Pasteur de Lille, France.

Source

Clin Exp Allergy, 1996 Oct, 26:10, 1119-24

Abstract

BACKGROUND: Recognition of antigen bound to the major

histocompatibility complex by the T cell receptor is insufficient to

lead to T cell proliferation and effector function, which require

co-stimulatory signals, such as those resulting from the interaction of

CD28 expressed on T lymphocytes and CD80/CD86 expressed on APCs. Lack

of interaction between these accessory molecules during antigen

stimulation leads to a state of antigen-specific lymphocyte

unresponsiveness. Previous studies have shown that rush venom

immunotherapy decreases venom-specific T cell proliferation very early

after the initiation of the rush. OBJECTIVE: In order to see whether

this hyporeactivity was associated with a down regulation of accessory

molecules, we studied CD28 surface expression on T lymphocytes from 10

non-atopic controls and from 10 non-atopic patients undergoing rush

venom immunotherapy. METHODS: Peripheral blood samples were collected

before the rush (day 0), at the end of the rush (day 1), at day 15 and

at day 45. CD28 expression was analysed using flow cytometry with

double labelling of the CD4+ and CD8+ lymphocyte subpopulations.

RESULTS: At baseline CD28 was expressed at a higher level on T

lymphocytes from allergic patients than from control subjects (P <

0.04) and in particular on the CD8 subset (P < 0.01), reflecting a

decrease in the suppressive CD8+CD28- subpopulation. No changes were

found in the percentages of total CD28+ T cells, CD4+CD28+ or CD8+CD28+

cells at the different time points after the initiation of of

immunotherapy. CONCLUSION: These results suggest that the CD28 pathway

is probably involved in the development of allergic reactions, but at

least at the phenotypic level, CD28 expression remained unchanged after

rush venom immunotherapy.

Language of Publication

English

Unique Identifier

97068419

4. Effect of immunotherapy on sCD23 levels in patients allergic to

Hymenoptera venom.

Author

Forman_SO; Reddy_MM; Mazza_DS; Meriney_DK; Grieco_MH

Address

R A Cooke Institute of Allergy, St. Luke's-Roosevelt Hospital Center,

Columbia, University College of Physicians & Surgeons, New York, New

York, USA.

Source

Ann Allergy Asthma Immunol, 1996 Oct, 77:4, 282-4

Abstract

BACKGROUND: sCD23 is the designation given to the low affinity IgE

receptor. The soluble fragment of this receptor (sCD23) participates in

the regulation of IgE synthesis. OBJECTIVE: The purpose of this study

is to examine the effect of a venom immunotherapy regimen on sCD23

levels. METHODS: We measured sCD23 levels by ELISA in Hymenoptera

venom-allergic patients (positive skin tests and a history of systemic

reactions to Hymenoptera sting) in serial sera collected over a course

of venom immunotherapy with a mean duration of 54 months. Mean

pre-sCD23 and post-sCD23 levels were compared using a Student's

two-tailed t test. RESULTS: sCD23 levels were found to be unchanged

over the course of venom immunotherapy. CONCLUSIONS: This is the first

longitudinal study that has been done. It suggests that while both

immunotherapy and sCD23 are known to be involved in the regulations of

IgE synthesis in the atopic patient, the immunomodulation seen in venom

immunotherapy is not mediated through sCD23 in any simple regulatory

manner.

Language of Publication

English

Unique Identifier

97040491

The use of standardized allergen extracts

Position statement of the AAAA&I. J Allergy Clin Immunol 1997;99:583-586 (may 1997)

Guidelines for the use of Allergen Immunotherapy, CMAJ May 1, 1995;152(9) p1413.

Filderman, RB., Immunotherapy Dos and Donts, Appendix, CMA Disease Management Patient Counselling Series-Allergic Rhinitis-Diagnosis and Treatment in Family Practice, Grovesnor House Press 1994, p 87.

Rose G, Arlian L, Bernstein D, Grant A, Lopez M, Metzger J, Wasserman S, Platts-Mills TA: Evaluation of household dust mite exposure and levels of specific IgE and IgG antibodies in asthmatic patients enrolled in a trial of immunotherapy. J Allergy Clin Immunol 97:5, May 1996 p. 1071.

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