Reviewers’ Comments
Allergy
PATHOPHYSIOLOGY
PHENYLPROPANOLAMINE INCREASES PLASMA
CAFFEINE LEVELS
Lake CR, Rosenberg DB, Gallant 5, Zaloga G, Chernow B. Clin Pharmacol Ther. 1990;47:675-685
Purpose of the Study
The purpose of the study was to examine the possible pharmacokinetic interaction of concurrent theophylline and caffeine administration.
Study Population
Sixteen healthy subjects (13 men, 3 women) were included in the study. Subject caffeine consumption ranged from 20 to 1200 mg/d (mean, 251 ± 73 mg/ d). Seven subjects smoked at least a half pack of cigarettes per day.
Methods
The subjects received each of the following drug combinations on a one-time basis in a double-blind, crossover fashion: 400 mg of caffeine, 400 mg of caffeine in combination with 75 mg of phenylpropa-nolamine, and placebo. Ten of the subjects completed all four drug combinations. One subject received three drug combinations, three subjects received two drug combinations, and two subjects received one drug combination.
Serum was collected 5 minutes before drug admin-istration, and at 1/2, 1, 11/2, 2, 3, 4, and 5 hours after drug administration. The serum was assessed for caf-feine, norepinephrine, and epinephnne levels. Heart rate and blood pressure were measured 21/2 and 5 minutes for drug administration and at 15-minute intervals for 5 hours after drug administration. The patients also filled out a 21-item mood and physical symptoms questionnaire 25 minutes before receiving the medication and 11/2 and 4 hours after its admin-istration.
Findings
Caffeine levels after ingestion of the phenylpropa-nolamine-caffeine combination were significantly higher than those of the other drug combinations from 1 to 5 hours after administration. The mean peak caffeine level after
phenylpropanolamine-caf-feine administration was 8.0 ± 2.2 g/mL compared to 2.1 ± 0.03 g/mL (P < .01) after caffeine admin-istration. The subjects in the
phenylpropanolamine-caffeine-treated group also had greater increases in systolic blood pressure and increased complaints of physical symptoms (eg, heart pounding, difficulty sleeping).
Many Americans consume the combination of caf-feine and phenylpropanolamine at the doses utilized in this study. One could easily ingest these doses with the combination of four to six cups of coffee and one tablet of a commonly prescribed oral decongestant.
Caffeine is by no means an innocuous drug. It has numerous side effects including cardiovascular stim-ulation with insomnia, anxiety, paroxysmal tachy-cardia, premature ventricular contraction and rarely death. The patients in this study receiving the phen-ylpropanolamine-caffeine combination reported more side effects than those receiving the other drug combinations. It would be prudent for physicians to warn patients given phenylpropanolamine prepara-tions about the potential risk of excessive caffeine consumption.
MICHAEL KEILEY, MD
STANLEY SZEFLER, MD Denver, CO
THE INFLUENCE OF CAFFEINE ON THE
STEADY-STATE PHARMACOKINETICS OF
THEOPHYLLINE
Jonkman JHG, Sollie FAE, Sauter R, Steinijans VW.
Clin Pharmacol Ther. 1991;49:248-255
Purpose of the Study
The purpose of the study was to explore the phar-macokinetics of theophylline with and without con-current multiple-dose administration of caffeine. Study Population
Eight healthy nonsmoking adult male volunteers were included in the study.
Methods
phar-macokinetic parameters were calculated for both study periods: area under the curve, total body clear-ance, and elimination rate constant.
Findings
During the period with concurrent caffeine admin-istration, the average theophylline plasma concentra-tion was increased by 23% (P < .01), the apparent clearance of theophylline was reduced by 29% (P <
.01), and the apparent elimination rate constant was reduced by 31% (P > .01).
The explanation for this rise in serum theophylline may be twofold: (1) caffeine is inhibiting theophylline clearance, (2) caffeine is being converted directly to theophylline.
Reviewers’ Comments
The potential of caffeine in relevant quantities (300 mg of caffeine by mouth three times a day is equiv-alent to 6 to 10 cups of brewed coffee per day) to decrease theophylline clearance and consequently raise serum theophylline levels is significant and of the same order of magnitude as erythromycin’s ability to elevate serum theophylline levels. The clinical im-plications are twofold. First, one should caution pa-tients already on therapeutic theophylline doses about the potential for theophylline toxicity if their caffeine consumption abruptly increases. Second, in those pa-tients starting theophylline who consume large amounts of caffeine (6 to 10 cups of coffee per day) the theophylline dose should be reduced by approx-imately 25%, theophylline levels should be followed closely, and symptoms of theophylline toxicity should be assessed carefully.
MICHAEL KEILEY, MD
STANLEY SzEFLF.R, MD Denver, CO
HOUSE DUST MITE ALLERGENS ON DIFFERENT
TYPES OF MATTRESSES
Mosbech H, Jensen A, Heinig JH, Schou C. Clin Exp Allergy. 1991;21:351-355
Purpose of the Study
The purpose of the study was to investigate
whether different types of bed mattresses result in
differences in the occurrence of dust mite major
al-lergens in mattress dust. Methods
Dust sampling was done on three different mattress surfaces. Concentrations and amounts of the major allergens for Dermatophagoides pteronyssinus, Derma-tophagoides farinae, and Dermatophagoides microceras
were measured using an enzyme-linked immunosor-bent assay technique. The mattresses were found in homes in the same geographic area. These homes were selected from a list of customers provided by three firms selling different types of mattresses. Twenty-two water mattresses, 12 spring mattresses,
and 1 7 foam mattresses were studied. The homes containing the different mattresses were found to be comparable with regard to age of mattress, use and age of underblankets, size of carpets, type and age of heating, ventilation, and occurrence of pets in the bedroom.
Findings
The concentration of the different mite allergens did not differ significantly between the different mat-tresses. Interestingly, the lowest concentration of al-lergens was found in the mattresses using underblan-kets as compared with the group of mattresses with-out such protection.
Reviewer’s Comments
Allergists have often advised the use of waterbeds to help dust mite control in the bedroom. It has been a well-held notion that mite growth is reduced when a waterbed mattress is utilized in contrast to a spring or foam mattress. Therefore, it was somewhat sur-prising that no difference in mite concentrations were registered between the three mattress types in the study. The use of a synthetic underblanket did seem to make a difference with regard to mite allergen load. It was speculated that human dander is depos-ited on this underblanket; and, by washing, this dan-der is removed, thereby reducing the availability of a major food for the dust mite.
MICHAEL J. WELCH, MD San Diego, CA
INTRAOPERATIVE ANAPHYLAXIS: AN
ASSOCIATION WITH LATEX SENSITIVITY
Gold M, Swartz JS, Braude RM, Dolovich, J, Shandling B, Gilmour RF. J Allergy Clin Immunol. 1991;87:662-666 Study Population
Fifteen patients (9 males, 6 females; ages 2 to 15 years) who had 19 episodes of intraoperative anaphy-laxis (IOA) from July 1985 to September 1989 were evaluated for latex (rubber) sensitivity.
Method
Skin tests were performed to raw natural latex, varying dilutions of anesthetic agents, and common allergens 6 weeks after IOA. Latex radioallergosor-bent test was also performed.
Findings
positive latex skin and radioallergosorbent tests and negative skin tests to anesthetic agents.
Conclusion
Patients with latex sensitivity are at risk for ana-phylaxis from intraoperative exposure to latex.
Reviewer’s Comments
Despite nearly 100 years of use, latex sensitivity is a newly recognized phenomenon with more than 50 cases reported in the last 3 years. Most cases have occurred in patients with spina bifida or urologic abnormalities or in health care workers. Every mye-lodysplasia clinic should evaluate their patients for this problem because premedication with antihista-mines and corticosteroids and avoidance of latex products (gloves, anesthetic equipment, latex parts on intravenous equipment) in the operating room may prevent a tragedy.
DAVID F. Gi&vr, MD Minneapolis, MI
ALLERGIC REACTION TO LATEX; A RISK
FACTOR FOR UNSUSPECTED ANAPHYLAXIS
Warpinski JR, Folgert J, Cohen M, Bush R. Allergy
Proc. 1991;12:95-102 Purpose of the Study
The purpose of the study was to report allergic reactions to latex in four individuals and to discuss the immunologic mechanisms involved.
Study Population
Four atopic patients with symptoms of rhinitis, anaphylaxis, and/or urticaria upon contact with latex products were studied.
Methods
Case histories of the four individuals were reported briefly. Case 1 involved a 30-year-old man with asthma and allergic rhinitis who developed contact urticaria from latex gloves and lip angioedema when blowing up balloons. Case 2 involved a 10-year-old atopic boy who developed angioedema of the lips when blowing up balloons. Case 3 involved a 30-year-old atopic physician with hand eczema who developed localized urticaria when he wore latex gloves. Case 4 involved a 20-year-old dental assistant who developed hand dermatitis, lip and facial an-gioedema from latex contact. Radioallergosorbent testing to latex was carried out in all four individuals. Findings
The patients showed IgE binding to latex radioal-lergosorbent test disks ranging from 1.0 to 27.3 times the negative control. Latex products directly bound IgE from all four patients. These and other tests indicate that latex-allergic patients have IgE directed against specific latex proteins and that allergy to latex
can pose a substantial health risk to susceptible mdi-viduals.
Reviewer’s Comments
This was an excellent study and pointed out the need for a detailed history of possible contact sensi-tivity as a cause of unexplained urticaria and anaphy-laxis. There are similar reports in the literature of topical bacitracin ointment doing the same thing.
JAY E. SELCOW, MD
West Hartford, CT
ALLERGIC REACTIONS TO LONG-TERM
BENZATHINE PENICILLIN PROPHYLAXIS FOR
RHEUMATIC FEVER
International Rheumatic Fever Study Group. Lancet.
1991;337:1308-1310
Purpose of the Study
To determine the true incident of allergic reactions to long-term prophylaxis with benzathine penicillin in patients with past rheumatic fever.
Study Population
1 790 patients who fulfilled the Jones criteria for diagnosis of rheumatic fever, none of whom had a
history of an allergic reaction to penicillin. Ages
ranged from 5 to 28 years, 33% were <12 years.
Methods
This prospective study took place during 2 years in which 1 790 patients received benzathine penicillin prophylaxis every 4 weeks for a total of 2736 patient-years of follow-up. Signs and symptoms of possible allergic reactions, ie, hypotension, dyspnea, pruritis, urticaria, angioedema, arthralgia, or maculopapular rash were recorded. Any reaction was classified ac-cording to time of onset: immediate (<1 hour); accel-erated (1 to 72 hours); and late (>72 hours). A total of 32 430 injections were given.
Findings
Conclusions
The incidence of allergic reactions (3.2%) observed in this study in patients on continuous prophylaxis with benzathine penicillin did not differ from the 2.24% reported in patients who received short-term therapy with benzathine penicillin (Clin Allergy.
188;18:515-540). Thus, the duration of previous treatment with benzathine penicillin does not appear to increase the risk of an allergic reaction. Moreover, the authors conclude that repeat exposure does not increase the occurrence of positive skin tests to peni-cillin. Anaphylaxis and death were also no more frequent in patients given only one course of penicillin vs patients who had had multiple courses.
Reviewers’ Comments
This study provides incidence figures for adverse reactions to penicillin in a large population followed prospectively for 2 years. The authors conclude that the incidence of serious reactions to penicillin, ie, anaphylaxis or death, are not changed significantly by repeat exposure to parenteral penicillin vs single exposure. Thus, long-term treatment with antibiotics such as penicillin will not make patients more likely TMto become allergic. Although the risk of serious reactions to penicillin must be kept in mind, one should not avoid repeat exposure to penicillin if nec-essary. However, because the route and frequency of drug administration can influence the type of immune response, these findings may be applicable to drugs when they are given orally.
KETAN K. Sm, MD
ROBERT F. LEMANSKE, JR., MD Madison, WI
ATOPY IN CHILDHOOD AND DIET IN INFANCY.
A NINE-YEAR FOLLOW-UP STUDY. 1. CLINICAL
MANIFESTATIONS
Poysa L, Korppi M, Remes K, Juntunen-Backman K.
Allergy Proc. 1991;12:107-111.
Purpose of the Study
The purpose of the study was to evaluate the effectiveness of diet in preventing or reducing atopic symptoms in childhood in Finland.
Study Population
The study group included 119 children with and without family history of atopy.
Methods
Half the atopy-prone children kept to a diet in-tended to prevent atopy, ie, breast-feeding prolonged up to age 3 months and introduction of solid foods and formulae based on cow milk after age 3 months. All children were examined at ages 5 and 10 years. In addition to clinical examination and interview, skin-prick tests using eight common inhalant aller-gens were performed.
Findings
At age 9 to 10 years, 38 (32%) of the 1 19 children exhibited at least one atopic illness (bronchial asthma, allergic rhinitis, allergic conjunctivitis, atopic eczema, or food allergy). Forty percent of children with family histories of atopy had atopic illnesses, independent of diet in infancy. The occurrence of atopic manifes-tation in the children of nonatopic families was 21%. Only half the children who had atopic symptoms at age 1 2 months had symptoms 9 years later. Asthma, allergic rhinitis, and positive skin-prick test results at age 5 years, however, correlated well with the sub-sequent occurrent of respiratory allergy.
Conclusions
The preventive measures in early infancy intended to reduce the risk of atopy had no influence on atopic manifestation 9 years later.
JAY E. SELCOW, MD
West Hartford, CT
CHARACTERISTICS OF PATIENTS WITH
FOOD-RELATED COMPLAINTS
Parker SL, Leznoff A, Sussman GL, Tarlo SM, Krondl M. I Allergy Clin Immunol. 1990;86:503-511.
Purpose of the Study
The purpose of the study was to characterize the nature of patients reporting adverse reactions to foods.
Study Population
Forty-five adults ages 1 8 to 60 years of age were recruited from allergy clinics for suspected adverse reactions to foods.
Methods
The patients were separated on the basis of a comprehensive clinical history, skin testing, and pla-cebo-controlled double-blind food challenges into two groups. Patients with reactions highly suggestive of IgE-mediated food hypersensitivity numbering 22 and patients with atypical adverse results that could not be confirmed by double-blind food challenge numbering 23. Skin testing was done by the prick technique with a wheel reaction with net diameter of 3 mm and larger than control considered positive. Double-blind placebo-controlled food challenges, when they were not life-threatening, were performed in the typical fashion.
Findings
head-ache, etc, gastrointestinal, generalized bloating, ab-dominal distension, and gas and a number of
non-groupable symptoms including chills,
hyperirritability, mood swings, hearing impairment, memory loss, etc. Foods causing most prominent symptoms among patients in Group A included leg-umes, tree nuts, crustacea, and fish. In Group B, milk, white sugar, wheat, egg, smoked or cured meat, and yeast were among the most troublesome foods re-ported. All but one patient in Group A gave a positive skin test response to food. Only four patients in Group B had a positive response.
The double-blind placebo-controlled food chal-lenges were universally negative in Group B. Patients in Group A were more likely than patients in Group B to report having experienced eczema, hayfever, episodes of wheezing. Overall, patients in Group B reported significantly more offending foods than pa-tients in Group A, on the average as many as five times more foods involved. The authors conclude that clinical findings in this study indicate that patients referred to allergists for suspected adverse reactions to foods represent two distinctly different groups: one group in which the bulk of evidence supports the IgE-dependent immediate hypersensitivity food al-lergic reactions, and the second group which includes patients in who symptomatology in offending foods are incompatible with classic IgE-mediated food al-lergy and in whom food challenges are negative. Reviewer’s Comments
Although this article exclusively involved patients older than 1 8 years, it very nicely summarizes pre-vious data detailing the types of foods, the number of foods, the types of symptoms, positive skin test and challenge one would expect to find in IgE-me-diated disease and in non-IgE-mediated, purported adverse reactions to foods. Perhaps the most eluci-dating portion of this article is the discussion whereby there is an excellent hypothesis put forth explaining why certain foods especially yeast were identified in the B group of patients and why there appeared to be similar symptoms in other family members in this group. Another interesting finding is the fact that a larger portion of patients in Group B than in Group A have reported adverse reactions of the popular press. The authors conclude that negative double-blind challenges may help to convince such patients as Group B that they are not sensitive to suspected food and therefore, may afford clinical and social benefits.
MAE1mI I. SACH5, PHD, DO Rochester, MN
ALLERGENICITY OF ORALLY ADMINISTERED
IMMUNOGLOBULIN PREPARATIONS IN
FOOD-ALLERGIC CHILDREN
Bernihisel-Broadbent J, Yokien RH, Sampson HA.
Pediatrics. 1991;87:208-214. Purpose of the Study
Orally administered immunoglobulin preparations derived from bovine milk, chicken egg, and human
sera were used for passive immunization for preven-tion and therapy of enteric disease. An in vitro study with sera from milk and egg-allergic patients was performed to determine the allergic potential of these immunoglobulin preparations.
Study Population
Twenty-two milk allergic and 28 egg-allergic pedi-atric patients with documented hypersensitivities to these food allergens were included in the study. Pa-tients were referred to the Pediatric Allergy Clinic because of severe atopic dermatitis and/or a history of allergic reactions to foods. Sensitivity was docu-mented by double-blind placebo-controlled food challenges. Control sera from five nonatopic individ-uals, a peanut-allergic atopic patient, and an atopic patient who was not food-allergic were utilized.
Methods
Protein extracts of milk, bovine immunoglobulin, egg white, human immunoglobulin, and five egg yolk anti-immunoglobulun preparations were bound to nitrocellulose paper. The extracts were incubated with sera from milk-allergic and egg-allergic patients to probe for IgE binding. Human IgE was then added with alkaline phosphatase in typical enzyme-linked immunosorbent assay fashion and analyzed by deter-mining the optical density of each dot.
Polyacrylamide gel electrophoresis also was per-formed to probe the patient’s sera for antigen-specific IgE binding to the protein band. Subsequent Western blot analysis was performed to establish binding of bovine ‘y-globulin. The chicken egg immunoglobulins were confirmed by probing a panel with alkaline phosphatase-labeled goat anti-chicken IgG.
Findings
Fifteen of 28 egg-allergic patients had the specific IgE binding against one or more egg yolk-binding antiviral chicken immunoglobulins. Western blot analysis in milk-allergic and egg-allergic patients demonstrated IgE antibodies for both bovine and chicken immunoglobulin molecules. Sera from egg-allergic and milk-allergic patients had no detectable IgE binding against the human immunoglobulin prep-arations.
Conclusions
These data indicate that administration of antibody preparations derived from bovine or chicken compo-nents may lead to potential allergic reactions in milk-or egg-sensitized patients. They may also sensitize in some nonallergic individuals. In contrast, human im-munoglobulin preparations can be administered with minimal risk in milk- or egg-sensitized patients.
CHRISTOPHER RANDOLPH, MD
ENVIRONMENTAL ASSAY FOR COCKROACH ALLERGENS
Schou C, Fernandez-Caldas, E, Lockey RF, Lowenstein H. J Allergy Clin Immunol. 1991;87:828-834.
Purpose of the Study
The purpose of the study was to design an assay that would directly measure the concentration of cockroach allergens in extracts of environmental dust. Methods
Purified cockroach allergen Per a I from P americana
was used as a reference antigen in the quantitation of allergen in extracts of dust samples. Vacuum cleaner bags containing dust from 73 homes were collected in the Tampa area. Cockroaches are not found as household pests in Greenland. Six vacuum cleaner dust samples from Greenland were included as neg-ative controls. A sandwich enzyme-linked immuno-sorbent assay was used to measure the concentration of cockroach allergens in the various samples. The sensitivity of this assay was 0.2 ng Lowry protein of Per a I Eq/mL corresponding to 1 ng of Per a I Eq/g of dust.
Findings
The assay did not react with non-cockroach aller-gen sources. Dust samples from 73 households from Tampa varied from below detection to 200 000 ng of Per a I Eq/g of dust. All Greenland homes as well as two American homes contained cockroach allergen concentrations below the lower detection limit that is less than 1 ng of Per a I Eq/g. Three commercial cockroach allergen extracts all contained the allergen detected by this assay.
Conclusions
This assay has the potential value for studying clinically relevant cockroach allergen exposure levels and for assessment of efficacy of allergen avoidance measures. Furthermore, this assay could be used for sanitary documentations in bakeries, restaurants, etc. The assay is fast and sensitive. It represents another report of the ability to determine very small quantities of significant allergen as previously reported for house dust mite and peanut.
MARTIN I. SAcH5, PHD, DO Rochester, MN
TREATMENT
AIRBORNE CAT ALLERGEN (FEL D I)
ENVIRONMENTAL CONTROL WITH THE CAT IN
SITU
deBlay, F, Chapman MD, Platts-Mills TAE. Am Rev
Respir Dis. 1991;143:1334-1339. Purpose of the Study
The purpose of this study was to define more precisely the contributions of furnishings, air filters,
room ventilation, and the cat itself to airborne cat allergen.
Methods
Air sampling was carried out using a cascade im-pactor which was loaded with glass disks coated with 5% agarose-sorbitol gel in borate-buffered saline at each of its four stages, which collected particles less than 2.5 tm to greater than 6 m. Fel d I was measured utilizing a two-site monoclonal antibody-based enzyme-linked immunosorbent assay tech-nique. Experimental design involved placing a cat for 20 hours per day in a 33-m2 room, which was either unfurnished (carpets covered with hard board and plastic sheeting and chair was metal) for 67 days or a furnished setting (carpets exposed and chair covered with synthetic sheet) for 79 days. Airborne Fel d I allergen was monitored utilizing different room yen-tilation rates (room fan and window), HEPA filter air cleaner (Enviracaire), and HEPA vacuum cleaner (Model GS-90, Nilfisk, Inc).
Findings
Introduction of the cat into a room was associated with an increase of Fel d I to approximately 60 ng/ m3 within 30 minutes with less than 10% coming from the cat’s breathing, presumably saliva. Weekly bathing was very effective in decreasing airborne allergen, particularly small particles (2.5 m diam-eter) by 90% with modest reaccumulation between washes. The carpet effect was profound with accu-mulation of allergen 100 times higher with carpet than with plastic sheeting. Ventilation rate influenced airborne particle size and total amount with slow rates giving a higher percentage of small particles and greater total particle count with fast rates. The air filter run at either high or low rates for 3 hours was most effective (decreased airborne allergen by 98%) in the unfurnished room where the plastic floor was also vacuumed for 15 minutes.
Conclusions
Based on this study, the following procedures are recommended to reduce airborn cat allergen levels: (1) remove cat completely or keep outdoors; (2) use polished floors with carpeting; (3) minimize uphol-stered furniture; (4) use a vacuum cleaner and an air purifier with a high energy particulate air filter; (5) wash cat weekly.
Reviewer’s Comments
Allergens, and Washing the Cat. Am Rev Respir Dis.
1991;143:1209-1210).
STANLEY P. GALANT, MD Orange, CA
CLINICAL EVALUATION OF A DOUBLE-BLIND
DUST MITE AVOIDANCE TRIAL WITH
MITE-ALLERGIC RHINITIS PATIENTS
Kniest FM, Young E, VanPraag MCG. Clin Exp Allergy.
1991;21:39-47.
Purpose of the Study
This study was designed to investigate the value of using a dust mite killing agent (in conjunction with intensive cleaning) on symptoms of allergic rhinitis. Previous studies have shown a definite benefit of strict dust avoidance measures including the use of a mite biocidal agent in patients who have asthma. Less information is known about the impact of an acaricide on patients suffering from rhinitis.
Methods
Twenty subjects with persisting allergic rhinitis symptoms were selected. They lived in 20 different dwellings and were all sensitized to house dust mite as determined by skin tests and radioallergosorbent tests. Half of the 20 households carried out intensive cleaning with acaricide (solidified benzylbenzoate). Daily symptoms and medications score along with guanine and dust exposure were compared between the two groups.
Findings
Symptom scores dropped significantly, as did the total IgE and exposure to dust and mite products in the acaricidal cleaner treatment group. After one year, the daily symptoms median was 47% and exposure to dust and mite products (ie, guanine exposure) was 53% better or lower than in the controls.
Reviewer’s Comments
Intensive cleaning with acaricidal treatment per-formed twice a year resulted in significant clinical improvement in patients with allergic rhinitis. The acaricide used was Acarosan which was applied as either a foam or a powder. The active ingredient is benzylbenzoate. The foam was sprayed primarily onto the mattress, upholstery, carpet or rug, and distributed evenly with a scrubbing brush. After a drying period, the powder was removed by vacuum cleaning. These findings support the previous re-ported clinical improvements in asthma after mite avoidance measures utilizing the acaricide cleaner Acarosan. The acaricidal cleaning method proved to be an effective and safe instrument in reducing mites and allergenic dust and, therefore, should benefit mite-allergic patients.
MICHAEL J. WELCH, MD San Diego, CA
THE VALUE OF IMMUNOTHERAPY WITH
VENOM IN CHILDREN WITH ALLERGY TO
INSECT STINGS
Valentine M, Schuberth K, Kagey-Sobotka A, Graft D, Kwiterovich K, Szklo M, Lichtenstein L. N Engl J Med.
1990;323:1601-1603.
Purpose of the Study
The purpose of this study was to determine if venom immunotherapy is necessary in all children with allergic reaction to hymenoptera stings.
Study Population
The study population comprised 242 children (2 to 1 6 years of age) with a history of cutaneous reactions (urticaria, pruritis, and/or angioedema) as their only manifestation of insect sensitivity.
Methods
All the patients had at least one positive venom skin test in addition to the appropriate clinical history. Of these patients, 45 were assigned randomly to venom therapy, 61 were assigned randomly to receive no therapy, whereas 23 chose to receive immuno-therapy and 1 13 chose not to receive immunotherapy.
Findings
The patients were followed up during a 4-year period. In the treatment group, 84 stings in 36 patients resulted in one systemic reaction (1 .2%, whereas 196 stings in 86 untreated children resulted in 1 8 systemic reactions (9.2%). The majority (16/18) of the reactions were milder and two were of the same severity.
Conclusion
Venom immunotherapy has been shown to be 97% to 99% effective in previous studies to protect against further systemic reactions. The low reaction rate in the untreated group and a lack of progression to more severe reactions suggests that this 2sub-group’ of hymenoptera-sensitive patients may not necessarily benefit from venom immunotherapy.
BRADLEY E. CHups, MD Sacramento, CA
EFFECT OF MATERNAL IMMUNOTHERAPY ON
IMMEDIATE SKIN TEST REACTIVITY, SPECIFIC
RYE I IgG AND IgE ANTIBODY, AND TOTAL
IgE OF THE CHILDREN
Glovsky MM, Ghekiere L, Rejzek E. Ann Allergy.
1991;67:21-24.
Purpose of the Study
Study Population
Criteria for the selection were that the mother was atopic and sensitive to grass or Chinese elm, the father was nonatopic, and that the mother received immu-notherapy (IT) during at least one and, preferably, more than one pregnancy. The children were divided into two groups: the mothers of 14 children received IT (Group A), and in 14 additional children (Group B) the mothers did not. Maternal and cord sera were obtained at deliver from 10 additional mothers and children.
Methods
Skin tests were performed by the prick method (1 :20 weight/volume glycerinated extract) and by the intradermal method (1 : 1 000 weight/volume) using several grasses, Chinese elm, house dust, and D fan-nae. Rye I IgG and IgE antibodies were measured by double antibody ratio immunoassay, while total IgE was measured using the PRIST method.
Findings
Prick and intradermal tests were performed on 24 children for grass pollen sensitivity. Two of 1 1 in Group A were positive compared to 9 of 13 in Group B (P < .05). A lower percentage was found in Group A vs Group B for Chinese elm and house dust (P>
.05), and no differences were seen for Dermatopha-goides farinae. In five families in which blood samples
were obtained, total IgE was 48 ± 28 ng/mL (X ± SEM) in Group A children and 1 64 ± 89 ng/mL in their Group B cohorts. In addition, IgE and IgG Rye I antibodies were analyzed in these families. Four of six children whose mothers were not immunized were “antibody positive” (by authors’ criteria) compared with 1 of 6 in the desensitized group. Of interest is the finding of severe rhinitis and/or asthma in 5 of 14 in Group A compared with 1 1 of 14 in Group B.
Reviewer’s Comments
This is an interesting study regarding an important clinical problem. In terms of the pregnant patient, IT is usually continued at the dosage which had been received safely prior to pregnancy. The dosage is not increased, nor is IT initiated during pregnancy, how-ever. What about the fetus? Following the clue from animal studies, one might expect tolerance to occur in utero during IT, although the feat that sensitization could occur also has some logic based on evidence of in utero sensitization, particularly to foods which the mother ingests. Glovsky’s data suggest partial toler-ance in some offspring. However, larger numbers are needed to confirm whether this phenomenon is real, whether it is specific, and what the mechanism might be. Double-blinded studies, if possible, would defi-nitely be helpful. Perhaps animal studies using models which have IgE-mediated disease could be utilized also.
STANLEY P. GALANT, MD Orange, CA
THE ASSOCIATION OF ALLERGEN SKIN TEST
REACTIVITY AND RESPIRATORY DISEASE
AMONG WHITES IN THE US POPULATION:
DATA FROM THE SECOND NATIONAL HEALTH
AND NUTRITION EXAMINATION SURVEY, 1976
TO 1980
Gergen PJ, Turkeltaub PC. Arch Intern Med.
1991;151:487-492.
Purpose of the Study
The purpose of this study was to evaluate the role that allergy, as defined by the degree of allergen skin test reactivity, played in influencing the prevalence of allergic rhinitis, chronic rhinitis, and asthma in the US population.
Study Population
This was a sample of the US population taken at 64 sampling sites during 1976 through 1980. Subjects, aged 1 2 to 74 years, were interviewed and eligible to receive allergen skin tests. Of the 12 727 individuals who participated, complete data on respiratory symp-toms, smoking, and skin test reactivity were available on 10 854 (85%). Diagnosis of allergic rhinitis, chronic rhinitis, and asthma were established.
Methods
Skin-prick testing was performed using eight aller-gens (1:20 w/v): house dust, cat, dog, Alternaria, mixed ragweed, oak, perennial rye grass, and Ber-muda grass. A positive reaction produced a mean erythematous diameter of >10.5 mm 20 minutes after allergen administration. Skin test reactivity to indoor (dust, cat, dog) and outdoor (Alternaria, pollens) aeroallergens were analyzed separately and in com-bination.
Findings
The prevalence of allergic rhinitis increased as al-lergen skin test reactivity increased, with the odds ratio exceeding 8 for the group with two or more positive tests. A significant association between asthma and allergen skin test reactivity was observed for all groups of nonsmokers. The association be-tween only asthma and skin test reactivity was not significant except in the 12- to 24-year age groups with two or more positive tests. The relationship of allergic diseases due to skin test reactivity based on the source of allergen exposure (indoor, outdoor, or both) was analyzed. Persons who reacted only to outdoor allergens, or both outdoor and indoor aller-gens, had an increasing prevalence of allergic rhinitis or asthma with increasing allergen skin test reactivity. Persons who reacted only to indoor allergens had no consistent increase in the prevalence of allergic rhi-nitis or asthma with increasing skin test reactivity. No significant association between chronic rhinitis with increasing allergen skin test reactivity was observed.
Conclusions
allergic rhinitis is present) with increasing allergen skin test reactivity, but not for chronic rhumtis. Reviewer’s Comments
Dr Turkeltaub appears to be the only living inhab-itant of the known universe who used erythema as the sole criteria for a positive skin test response. Erythema diameters of 10 mm would be considered very equivocal in most skin test grading systems. Nevertheless, the results clearly point to the impor-tance of allergy in childhood asthma. The adults with only asthma do not show associations with skin test reactions probably because the study did not distin-guish those with adult onset-type asthma, which is usually nonallergic. Those who reacted only to indoor allergens and those with chronic rhinitis showed no association with skin text reactivity most likely be-cause the most important perennial indoor allergen, house dust mite, was not included in the panel of allergens tested.
ALLEN D. ADINOFF, MD
Aurora, CO
EFFECTS OF MATERNAL DIET DURING LATE
PREGNANCY LACTATION ON THE
DEVELOPMENT OF IgE AND EGG-MILK-SPECIFIC
IgE ANTIBODIES IN INFANTS
Lilja G, Dannaeus A, Foucard T, Graff-Lonnevig V, Johansson SCO, Oman H. Clin Exp Allergy. 1991;21:195-202.
Purpose of the Study
This study attempts to define the risk of developing food allergy during the third trimester and early breast-feeding ages.
Study Population
The study population included 162 pregnant women with respiratory allergies who gave birth to 166 newborns.
Methods
The pregnant women were assigned randomly to a
late pregnancy diet, with either “reduced” or “high” quantity of cow milk and eggs. Serum samples were obtained at birth, 2, 6, and 18 months of age and analyzed for total IgE and egg/milk-specific IgE and IgG. Skin tests to ovalbumin, ovomucoid, and j3-lactoglobulin were done at 6 and 18 months of age. Findings
Serum IgE levels and egg/milk-specific IgE and IgG did not differ between the “reduced’ and the “high” groups. A claim is made for a relationship between IgE and IgG antibody response for egg but not for milk. This is based on the presence of serum IgE to ovomucoid along with significant higher serum IgG to ovomucoid at 6 and 18 months. There was good correlation between radioallergosorbent and skin-prick tests. The development of clinically noted atopy
was no different between the two groups. The authors note “determinations of IgG antibody levels to food allergens have only a limited value.’
Reviewer’s Comments
This study pessimistically supports the thesis that the atopic infant can’t be deterred from its genetic programming. However, the restriction of egg/milk was relative, and other potential sensitizers (food and inhalant) were not controlled. A suggestion of “high’ and “low’ responders with IgE and IgG to specific foods is only hypothetical because this was not sup-ported by the ovalbumin of i3-lactoglobulin data. Perhaps the measurement of IgG antibody to food should be considered of limited value even in re-search!
CLIFTON T. FURUKAWA, MD
Seattle, WA
Upper
Airway
Disorders
PATHOPHYSIOLOGY
LARYNGEAL CHANGES DURING EXERCISE AND
EXERCISE-INDUCED ASTHMA
Hurbis CG, Schild JA. Ann Otol Rhinol Laryngol.
1992;100:34-37.
Purpose of the Study
This study was performed to determine the effect
of exercise on the larynx in healthy and asthmatic
patients. Study Population
Thirty subjects aged 18 to 35 years were studied.
There were 15 healthy subjects and 15 with only
exercise-induced asthma. Methods
All subjects had an endoscopic examination of their laryngeal area where photographic images were re-corded for measurement of inspiratory and expiratory glottic areas. All were then exercised at 75% to 85% of their predicted maximum heart rate for 8 minutes, breathing cold dry air. Laryngoscopy and pulmonary functions were performed after 8 minutes of exercise and again after 5 minutes of rest.
Findings
In healthy individuals and in asthmatic patients
whose forced expiratory volume changed less than 5%, the laryngeal opening increased in size, whereas asthmatics whose forced expiratory volume dropped
in excess of 5% showed a narrowing of the glottic
area. Conclusions
