- Email: [email protected]
23. Biochemical and allergenic studies of vespid venoms
VOLUME fil NUMBER 3
pg/ml) were treated with lyophilized venoms from a commercial source with the use of the regimen we reported last year. Weekly injections were given until a maintenance 100 pg dose was reached, usually by 6 wk. When the first 3.5 patients were subjected to a sting challenge, we observed 5 minor and 2 significant (hypotensive) episodes-an incidence of failure (20%) clearly above our previous experience (5%). The reactions occurred in a subset of patients with histoiies of more severe reactions to previous stings (< O.OI); these 7 patients also had more local and/or mild systemic reactions during venom immunotherapy than those who tolerated a sting (p < 0.01). Re-evaluation of the venom preparations revealed that one contained less protein (Lowry) than labeled. The dose for maintenance was increased accordingly and an increase in IgG antibody noted. All subsequent sting challenges, including those in 4 of 7 of the original treatment failures, were successful. We have thus (inadvertently) examined the effect of two venom doses and found that the lower dose is not invariably protective. Based on these observations, we suggest that those patients with more severe histories or significant reactions during treatment may require more time and a higher venom dose to achieve protection. This study brings the general availability of commercial venom preparations considerably closer.
2-I.
enom
immunotherapy.
M.5., C. E. Arbesman, Buffalo, N. Y.
R. E. Reisman, M.D., and M. Lazell, B.S.,
Clinical and immunologic responses were monitored in 50 insect-sensitive patients receiving bee and yellow jacket venom immunotherapy. All patients had had anaphylactic reactions and had elevated serum levels of venom-specific IgE (RAST). Venom injections were given weekly starting at a dose of 0.001 pg. Maintenance injections of 50 pg or greater were given monthly. During the course of treatment 6 patients bad local reactions and 3 patients had mild systemic reactions. There were 37 patients in whom sequential antibody (Ab) studies were carried out over a 1- to 2-yr period of venom treatment. In the majority of patients venom-specific IgG was produced by immunizing doses above 1 pg. Highest titers were related to higher doses. Several patients had no G Ab response and several with initially elevated G Ab had a declining titer. Venom-specific IgE declined in 20 patients, remained unchanged in 13, and rose in 4. There was also considerable variability in the persistence of venom-specific IgE in untreated patients without further sting exposure. There was no relationship between E and G Ab titers except in 3 patients who had marked rise in both Abs following venom treatment. Eight patients received subsequent stings with no reaction. At the time of this uneventful sting, E and G Abs generally were mildly elevated. These studies suggest considerable variability in the immunoIogic response with or without venom therapy and suggest guidelines for degree and duration of therapy may have to be individualized.
22. Further clinical applicati measurement of venom-sp C. E. Arbesman, Buffalo, N.Y.
M.D., and R.
We have previously related the ievels and changes of venom-specific IgE to exposure to insect stings and diagnosis and therapy of stinging insect sensitivity. Pertinent further observations have now been made. Nine patients had elevated serum venom-specific IgE shortly after sting anaphylaxis. Antibody titers fell to insignificant levels within 3 to 18 mo in the absence of specific treatment. Two patients had subsequent uneventful stings. Two other patients were observed with elevated venom IgE 12 yr after the sting reaction without interval immunotherapy or stings. Thus, the persistence of IgE aw tibodies is variable. Three patients had moderate to marked IgE anamnestic responses following large local sting reactions; placing them at risk in the event of subsequent stings. Sixteen patients receiving whole body extract therapy for 1 to 10 yr had therapy discontinued because of insignificam venom antibodies. Gne patient was identified who had eIevated bee body IgE and no venom IgE perhaps as a result of sensitization to whole body extract immunotherapy. Fourteen patients were seen shortly after yehow jacket sting anaphylaxis. Although direct skin tests were positive in all but two, bee, yellow jacket, and hornet venomspecific IgE could not be detected by the radioallergosorbent test (RAST). This group of patients requires further immunologic investigation. Further studies are needed of the natural lnstory of stinging insect sensitivity and the relationship to immunologic parameters.
23. Biochemical vespid venoms. Greenville,
and allergenic Donald
studie
R. Hoffman,
Ph.D.,
N. C.
Yellow jacket and yellow hornet venoms obtained by puncture of venom sacs were studied by enzyme electrophoresis, immunodiffusion and radioallergosorbent test (RAST) with sera from allergic individuals. The enzymes phospholipase A and B, hyaluronidase, and acid phosphatase were found in both venoms. Venoms from me two species could be distinguished by electrophoretic patterns, gel filtration profiles, hyaluronidase activity, and RAST. Two esterases were found in yellow jacket venom. Low levels of neutral protease, DNase, beta galactosidase, and histidine decarboxylase were detectable in both venom preparations; some of these low levels of enzymes could be derived from lyosomes and released as a result of tissue destruction. The vespid venoms contain about one tenth the enzyme activities of bee venom with the exception of hornet hyaluronidase which is comparable in activity to that in bee venom. Partially purified fractions of yellow jacket venom were tested by RAST with 20 sera from allergic individuals. Each serum gave at least 4% specific binding to whole yel-
1
American
Academy
J. ALLERGY CLN.
of Allergy
low jacket venom, and this binding was inhibitable by fluidphase yellow jacket venom. The RAST results indicate that there are at least four distinct allergens in yellow jacket venom, one of which is phospholipase, and that yellow jacket and yellow hornet venoms are biochemically as well as immunologically distinguishable.
~rnrn~~e response
to hymenoptera
Anne K. §obotka, Ph.D., Martin D Valentine, M.D., and Lawrence Lichtenstein, M.D., Baltimore, Md.
M.
We have studied the IgE and IgG antibody responses in 50 Hymenoptera-sensitive patients from initiation of immunotherapy to the end of 1 yr of monthly lOO+g (maintenance) doses of honeybee (HBV) or yellow jacket (YJV) venoms. The most striking observation is the divergence between me response to the two antigenic mixtures despite the similar immunization regimens used. With HBV the IgE response usually occurs prior to the increase in IgG; the IgE antibody (Ab) begins to fall by 3 mo while the IgG Ab persists at the peak level for a year. In the HBV-treated patients, the starting IgE antiphospholipase A (a-PLA) levels ranged from < 1 to 90 rig/ml and peaked at 36 to 280 rig/ml, The pretreatment IgG a-PLA range was
S The overcontrolling mother in ronchiai asthma. Howard S. Rubenstein, tanley H, King, Ph.D, Cambridge, Mass
and Emily
L. London,
childhood, we asked patients coming to a university health services clinic to answer a questionnaire anonymously. Three disease groups were studied-(l) bronchial asthma (30 patients), (2) perennial rhinitis (24), (3) seasonal rhinitis (19)-and a group of nonallergic healtby control subjects (24). Asthmatic patients significantly more often than subjects in the other groups reported that when they were children their mothers (but not their fathers) had overcontrolied them (p < 0.001). We conclude that asthmatic patients perceive their mothers as having overcontrolled them. Wbetber this perception in any way contributes to the pathogenesis of the disease is yet to be determined.
26. Middle lobe atelectasis in asthmatic patients. H. G. Altamiranor S. J. McGeady, M.D.# and H. C ~ansrna~R~ M.D., Philadelphia, Pa.
Rubenstein reported that patients with well-controlled bronchial asthma coming to a university health services clinic were more likely to arrive late for an appointment, or not to show up at all, than nonallergic healthy patients, patients with perennial rhinitis, patients with seasonal rhinitis, or patients being investigated for cardiac disease. He wondered whether such behavior might be retaliation against an overcontrolling mother. (Lancet 1: 1011, 1976.) To determine whether patients with bronchial asthma perceived their mothers as having overcontrolled them in
ir.,
Review of 41§ childhood asthma admissions revealed chest x-ray findings of right middle lobe (RML) atelectasis in 25 instances involving 18 patients. The mean age in the atelectasis group was 5.4 yr. Conservative management including bronchodilators (100% of patients), steroids (.56%), antibiotics (76%), chest physical therapy (28%), and postural drainage (60%) was used. Duration of hospitalization in atelectasis ranged from 3 to 16 days, with a mean of 8.5 days. RML atelectasis was resolved by follow-up x-rays in 17 of 25 patients at the time of discharge‘ Eight patients were discharged as asymptomatic, but with persistent radiographic atelectasis. Of these, 4 of 8 showed clearing cm follow-up x-rays, 2 of 8 remained asymptomatic but had not had follow-up x-rays, and 2 of 8 were lost to follow-up. We conclude that RML atelectasis is a common finding in childhood asthma (6% of admissions), particularly in younger patients. It may be recurrent in nature. Invasive procedures, such as bronchoscopy? bronchogram, and lobectomy, should be restricted to those patients with persistent disease.
27. Pneumomediastinum asthma. R. J. Dattwyler, M.D., A.B.
IMiWJNOL. MARCt! 137B
com~l~cat~n
MD., M.D., J. L. Ohman, M.D., J. Far M. Akbarian, M.D., and K. J. Woch, Boston, Mass.
M.D.,
Although pneumothorax is a relatively frequent complication of asthma or its treatment, pneumomediastinum is a relatively rare accompaniment of this disorder. We have observed 8 patients in whom pneumomediastinum developed during a episode of asthma. The principal symptom in these patients was the acute onset of severe retrostemal pain. All patients were dyspneic at the time of presentation, however, only one was in severe respiratory distress. Other prominent physical findings included the presence of subcutaneous air in the supraclavicular fossae and neck in 6 of the
pg/ml) were treated with lyophilized venoms from a commercial source with the use of the regimen we reported last year. Weekly injections were given until a maintenance 100 pg dose was reached, usually by 6 wk. When the first 3.5 patients were subjected to a sting challenge, we observed 5 minor and 2 significant (hypotensive) episodes-an incidence of failure (20%) clearly above our previous experience (5%). The reactions occurred in a subset of patients with histoiies of more severe reactions to previous stings (< O.OI); these 7 patients also had more local and/or mild systemic reactions during venom immunotherapy than those who tolerated a sting (p < 0.01). Re-evaluation of the venom preparations revealed that one contained less protein (Lowry) than labeled. The dose for maintenance was increased accordingly and an increase in IgG antibody noted. All subsequent sting challenges, including those in 4 of 7 of the original treatment failures, were successful. We have thus (inadvertently) examined the effect of two venom doses and found that the lower dose is not invariably protective. Based on these observations, we suggest that those patients with more severe histories or significant reactions during treatment may require more time and a higher venom dose to achieve protection. This study brings the general availability of commercial venom preparations considerably closer.
2-I.
enom
immunotherapy.
M.5., C. E. Arbesman, Buffalo, N. Y.
R. E. Reisman, M.D., and M. Lazell, B.S.,
Clinical and immunologic responses were monitored in 50 insect-sensitive patients receiving bee and yellow jacket venom immunotherapy. All patients had had anaphylactic reactions and had elevated serum levels of venom-specific IgE (RAST). Venom injections were given weekly starting at a dose of 0.001 pg. Maintenance injections of 50 pg or greater were given monthly. During the course of treatment 6 patients bad local reactions and 3 patients had mild systemic reactions. There were 37 patients in whom sequential antibody (Ab) studies were carried out over a 1- to 2-yr period of venom treatment. In the majority of patients venom-specific IgG was produced by immunizing doses above 1 pg. Highest titers were related to higher doses. Several patients had no G Ab response and several with initially elevated G Ab had a declining titer. Venom-specific IgE declined in 20 patients, remained unchanged in 13, and rose in 4. There was also considerable variability in the persistence of venom-specific IgE in untreated patients without further sting exposure. There was no relationship between E and G Ab titers except in 3 patients who had marked rise in both Abs following venom treatment. Eight patients received subsequent stings with no reaction. At the time of this uneventful sting, E and G Abs generally were mildly elevated. These studies suggest considerable variability in the immunoIogic response with or without venom therapy and suggest guidelines for degree and duration of therapy may have to be individualized.
22. Further clinical applicati measurement of venom-sp C. E. Arbesman, Buffalo, N.Y.
M.D., and R.
We have previously related the ievels and changes of venom-specific IgE to exposure to insect stings and diagnosis and therapy of stinging insect sensitivity. Pertinent further observations have now been made. Nine patients had elevated serum venom-specific IgE shortly after sting anaphylaxis. Antibody titers fell to insignificant levels within 3 to 18 mo in the absence of specific treatment. Two patients had subsequent uneventful stings. Two other patients were observed with elevated venom IgE 12 yr after the sting reaction without interval immunotherapy or stings. Thus, the persistence of IgE aw tibodies is variable. Three patients had moderate to marked IgE anamnestic responses following large local sting reactions; placing them at risk in the event of subsequent stings. Sixteen patients receiving whole body extract therapy for 1 to 10 yr had therapy discontinued because of insignificam venom antibodies. Gne patient was identified who had eIevated bee body IgE and no venom IgE perhaps as a result of sensitization to whole body extract immunotherapy. Fourteen patients were seen shortly after yehow jacket sting anaphylaxis. Although direct skin tests were positive in all but two, bee, yellow jacket, and hornet venomspecific IgE could not be detected by the radioallergosorbent test (RAST). This group of patients requires further immunologic investigation. Further studies are needed of the natural lnstory of stinging insect sensitivity and the relationship to immunologic parameters.
23. Biochemical vespid venoms. Greenville,
and allergenic Donald
studie
R. Hoffman,
Ph.D.,
N. C.
Yellow jacket and yellow hornet venoms obtained by puncture of venom sacs were studied by enzyme electrophoresis, immunodiffusion and radioallergosorbent test (RAST) with sera from allergic individuals. The enzymes phospholipase A and B, hyaluronidase, and acid phosphatase were found in both venoms. Venoms from me two species could be distinguished by electrophoretic patterns, gel filtration profiles, hyaluronidase activity, and RAST. Two esterases were found in yellow jacket venom. Low levels of neutral protease, DNase, beta galactosidase, and histidine decarboxylase were detectable in both venom preparations; some of these low levels of enzymes could be derived from lyosomes and released as a result of tissue destruction. The vespid venoms contain about one tenth the enzyme activities of bee venom with the exception of hornet hyaluronidase which is comparable in activity to that in bee venom. Partially purified fractions of yellow jacket venom were tested by RAST with 20 sera from allergic individuals. Each serum gave at least 4% specific binding to whole yel-
1
American
Academy
J. ALLERGY CLN.
of Allergy
low jacket venom, and this binding was inhibitable by fluidphase yellow jacket venom. The RAST results indicate that there are at least four distinct allergens in yellow jacket venom, one of which is phospholipase, and that yellow jacket and yellow hornet venoms are biochemically as well as immunologically distinguishable.
~rnrn~~e response
to hymenoptera
Anne K. §obotka, Ph.D., Martin D Valentine, M.D., and Lawrence Lichtenstein, M.D., Baltimore, Md.
M.
We have studied the IgE and IgG antibody responses in 50 Hymenoptera-sensitive patients from initiation of immunotherapy to the end of 1 yr of monthly lOO+g (maintenance) doses of honeybee (HBV) or yellow jacket (YJV) venoms. The most striking observation is the divergence between me response to the two antigenic mixtures despite the similar immunization regimens used. With HBV the IgE response usually occurs prior to the increase in IgG; the IgE antibody (Ab) begins to fall by 3 mo while the IgG Ab persists at the peak level for a year. In the HBV-treated patients, the starting IgE antiphospholipase A (a-PLA) levels ranged from < 1 to 90 rig/ml and peaked at 36 to 280 rig/ml, The pretreatment IgG a-PLA range was
S The overcontrolling mother in ronchiai asthma. Howard S. Rubenstein, tanley H, King, Ph.D, Cambridge, Mass
and Emily
L. London,
childhood, we asked patients coming to a university health services clinic to answer a questionnaire anonymously. Three disease groups were studied-(l) bronchial asthma (30 patients), (2) perennial rhinitis (24), (3) seasonal rhinitis (19)-and a group of nonallergic healtby control subjects (24). Asthmatic patients significantly more often than subjects in the other groups reported that when they were children their mothers (but not their fathers) had overcontrolied them (p < 0.001). We conclude that asthmatic patients perceive their mothers as having overcontrolled them. Wbetber this perception in any way contributes to the pathogenesis of the disease is yet to be determined.
26. Middle lobe atelectasis in asthmatic patients. H. G. Altamiranor S. J. McGeady, M.D.# and H. C ~ansrna~R~ M.D., Philadelphia, Pa.
Rubenstein reported that patients with well-controlled bronchial asthma coming to a university health services clinic were more likely to arrive late for an appointment, or not to show up at all, than nonallergic healthy patients, patients with perennial rhinitis, patients with seasonal rhinitis, or patients being investigated for cardiac disease. He wondered whether such behavior might be retaliation against an overcontrolling mother. (Lancet 1: 1011, 1976.) To determine whether patients with bronchial asthma perceived their mothers as having overcontrolled them in
ir.,
Review of 41§ childhood asthma admissions revealed chest x-ray findings of right middle lobe (RML) atelectasis in 25 instances involving 18 patients. The mean age in the atelectasis group was 5.4 yr. Conservative management including bronchodilators (100% of patients), steroids (.56%), antibiotics (76%), chest physical therapy (28%), and postural drainage (60%) was used. Duration of hospitalization in atelectasis ranged from 3 to 16 days, with a mean of 8.5 days. RML atelectasis was resolved by follow-up x-rays in 17 of 25 patients at the time of discharge‘ Eight patients were discharged as asymptomatic, but with persistent radiographic atelectasis. Of these, 4 of 8 showed clearing cm follow-up x-rays, 2 of 8 remained asymptomatic but had not had follow-up x-rays, and 2 of 8 were lost to follow-up. We conclude that RML atelectasis is a common finding in childhood asthma (6% of admissions), particularly in younger patients. It may be recurrent in nature. Invasive procedures, such as bronchoscopy? bronchogram, and lobectomy, should be restricted to those patients with persistent disease.
27. Pneumomediastinum asthma. R. J. Dattwyler, M.D., A.B.
IMiWJNOL. MARCt! 137B
com~l~cat~n
MD., M.D., J. L. Ohman, M.D., J. Far M. Akbarian, M.D., and K. J. Woch, Boston, Mass.
M.D.,
Although pneumothorax is a relatively frequent complication of asthma or its treatment, pneumomediastinum is a relatively rare accompaniment of this disorder. We have observed 8 patients in whom pneumomediastinum developed during a episode of asthma. The principal symptom in these patients was the acute onset of severe retrostemal pain. All patients were dyspneic at the time of presentation, however, only one was in severe respiratory distress. Other prominent physical findings included the presence of subcutaneous air in the supraclavicular fossae and neck in 6 of the