Asthma and Allergic Disease Centers Workshop Lur A. Froehlich,
M.D.
Helicesdu,
Xd.
The Asthma and Allergic Disease Centers Workshops, held at thcb National Institutes of Health and sponsored by the National Institute of Allerg?: and Infectious Diseases, arp an annual and eagerly anticipated cvcbnt for the Center program directors and their key staff. Thcsc. workshops provide a forum for free-flowing exchange of ideas, progress reports, discussion of mutual s&ntific and administrative problems pertinent to Center activities, and exploration of future possibilities for coordinated clinical trials. IIaving entered its fourth year. the program now can report substantial progress. 1.ndcr the cffcctivt chairmanship of Dr. K. Frank Austen, the participants of the most recent workshop provided material for an exciting and productive meeting. Some 72 scientists, representing various disciplines from 17 (Yetiters* in 13 of the IJnited States, gathered la& Deeember 5-6 in Bethesda to discuss their most recent findings in the study of allergic disorders. The discussions focua:d on three major topics. each the subject of a separate session. SESSION
I. lMMUUODERMATOLOOlC
D#QRDERS
I’. Kohler, of the IJniversity of Colorado, presented preliminary data on a series of patients with palpable purpura demonstrating nctrrotizing or leukocytoelastic vasculitis on skin biopsy. 1)cposition of immunoglobulins and C3 in vessel walls of both involved and uninvolved skin with frequent associated findings of cryoprotcins and histories of rrccAnt strcptococcal infection suggests that the illness is primarily the result of tissue damage mediated via immune complexes. A series of nonatopic females presenting with chronic refractory urticaria accompanied by arthralgias and elevated ~~rythrocyte sedimentation rates were studied by I. (:igli from Harvard. Skin biopsies indicate that this syndrome From the National lnstitutc of Allergy and Infectious Disease. Hecrivcd for publication Feb. 28, 1975. ‘Thr 17 Asthma and Allergic Disease Centers and their progrum directors are as follows: Robert B. Brighnm Hospital, Boston (Dr. K. Frank Au&en) ; Creighton University, Omaba (Dr. Robert R. Townley) ; Duke University Medical Center, Durham (Dr. Rebecca H. Buckley) .; The aood Samnritan Hospital, Baltimore (Dr. Philip 8. Norman) ; Louisiana State IJmoerdty, New Orleans (Dr. John Salv gio) ; Mayo Clinic and Foundation, Roeh. ester (Dr. Gerald J. Gleich) ; National Asthma 7 enter, Denver (Dr. Elliott Middleton, .7r.) ; National Jewish Hospital ond Research Center, Denver (Dr. Richard 9. Farr) ; Northwestern University, Chicago (Dr. Roy Patterson) ; Scrippe Clinic and Research Foundation, 1,s Jolla (Dr. John H. Vaughan) ; State University of Sew York, Buftalo (Dr. Carl 73. Arhesman) ; University of California, San Francisco (Dr. Oscar L. F’rick) ; University of Colorado, Denver (Dr. Henry N. Claman) ; University of Michigan Medical Center, Ann Arbor (Dr. Kenneth P. Ynthews) ; University of Wisconsin, 3iadison (Dr. Gharlas E. Reed) ; Waahington University, S1. Louis (Dr. Charles W. Parkor) ; and NIAID, Beth&a (Dr. Allen P. Kaplan). Vol. 55, No. 6, pp. 376-s??
VOLUME 55 NUMBER 6
Asthma
and Allergic
Disease
Centers
Workshop
373
may be a manifestation of underlying necrotixing angiitis with or without hyporomplementemia. In a study of mediator release in patients with cold urticaria, A. Kaplan, of NIAID, noted a rise in plasma histamine levels in all patients within 5 minutes after submersion. In some patients with cholinergic urticaria, histamine is released during exercise and many cases also had vibration-induced swelling. A relationship was suggested between cholincrgic nrticaria and familial vibratory angioedema. A possibility exists of another group of patients with vibration-negative cholinergic urticaria involving release of other mediators, such as serotonin. A. Kulczycki from St. Louis suggested that patients with cold urticaria may have an immunoglobulin with anti-IgE activity that is a cryoglobulin. He cautioned that donor serum be warmed before preparation for P-K testing. IgE levels studied by G. Gleich and his group at Mayo correlated with the extent of skin involvement but not with estimates of severity in patients with atopic dermatitis. IgE levels changed during the course of the disease without clear-cut patterns. Elevated IgE levels were demonstrated in a variety of inflammatory dermatoses. In a study of peripheral blood leukocyte and Iymphocyte CAMP metabolism, C. Parker, of Washington University, noted that in active atopic dermatitis and severe psoriasis alterations in adrenergic responsiveness occurred. In discussing this report, C. Reed, of Wisconsin, stated that resting levels of CAMP in epidermal slices were found by his group to be elevated and were further increased upon treatment with catecholamines over that seen in normal subjects. R. Buckley, of Duke, reported on extension of studies on patients manifesting the syndrome of dermatitis, extreme hyperimmunoglobulinemia E, undue susceptibility to staphylococcal and fungal infections, and marked delayed cutaneous anergy. No association between hyperimmunoglobulinemia E and HL-A specificity or haplotype was found. Observed anomalies of mixed leukocyte culture responsiveness taken together with abnormalities in immune responses to soluble antigens suggest that defects may exist in either the lymphocytes or in the macrophages of these patients. The identification of Clq, C3, and Factor B deposition in acantholytic areas of early oral and skin lesions in patients with pemphigus vulgaris, as well as deposition of IgG in intercellular substances of both pathologic and normal areas, was reported by R. E. Jordon of Mayo. Their studies suggest that immune complexes occur in both sera and blister fluids and that complement activation may play a role in the pathogenesis of pemphigus vulgaris. SESSION II. BIOCHEMICAL AND OF THE ATOPIC INDIVIDUAL
PHYSIOLOGIC
RESPONSES
0. Frick’s group from San Francisco, California were concerned with the possible role of cellular immunity in food allergy. Delayed-onset allergy was associated with negative skin tests, skin window eosinophilia, and antigeninduced histamine release from leukocytes. Utilizing the Clausen leukocyte inhibition factor test, positive findings with milk and corn were noted in two
374
Froehlich
1. ALLERGY
CLIN.
IMMUNOL. JUNE 1975
thirds of patients manifesting negative immediate and delayed skin tests and radioallergosorbent test (RAST). The possibility of ~llular immunt* reactions to foods in some patients with hypersensitivity is suggcqted hut does not provc~ a cause-effect relationship in the pathogenesis of this condition. Their investigations on nasal airway resistance mrasurctl from t,he slope of an oscill~copc tracing of transnasal pressure drop vs. na.sal air flow were disc*ussetl 1)~ K. Mathews, of the I!nivcrsity of Michigall. Th(a marked rcactivit) of the uos(l to csternal stimuli was cmphasizetl. \\‘hilc phcnylcphrinc gave iI J)rogressive dose-related decrease in nasal airway rcsistancth, isoprotercnol protlucctl incrcascs in some nonatopic and asymptomatic atopic sub.jtchts and failed to decrease rc>sistance in symptomatic atopic subjects. The stuclics of C. Parker, of \Vashington l!nivcrsity, on serum prostaglandiu levels in bronchial asthma suggest that the significantly higher J)rostaglandin F levels in asthmatics is presumably due to increased rclcarre from leukocytes OI platelets, with preliminary obstarvations indicating that both prostaglandin J*’ and prostaglandin E arc detec*tahlc in sputum. In a study of mediator-provoked bronchial challenges in asthmatic patirnt.s, n. Stevenson and C. Arroyavc, from Scripps, noted significant falls in complement activity in two thirds of patients with positive acroallergen challenges, with simultaneous activation of alternative pathway in some. In a selected group of asthmatic patients with evidence of rcaginica hypersensitivity, significant increases in histamine and lowered complement levels wcrc det.ectctl on13 during specific allergen bronchial challcngc and not during bronchospasm induced by methacholinc or during challenges against allergens to which no reaginic antibodies were identified. A system for grading mcthacholint~ dose-response curves in atopic. and nonatopic individuals has Hun developed hy R. Townlcy’s grouJ) from Creighton. Whereas former asthmatics, or asthmatics who have been in remission for longer than one year, fall into the high or medium categories of methacholine sensitivity and nonatopic individuals fall into negative categories, half of individuals with allergic rhinitis showed aI1 initial positive methacholinc inhalational response with a plateau J)hcnomenon in dose curves different from asthmatic patterns. This drop in FEV, remaining at a stable level despite additional methacholine inhalations suggested a feedback mechanism between heta adrenergic and cholinergic systems, interpreted to mean that these patients had sufficient intact beta adrenergic: receptors to counteract additional inhalations of methacholinc. R. Rosenthal, representing *Johns Hopkins, commented on their findings in which specific airway c*onductancc cahanges after inhalation challenge with mecholyl were similar in patients with hay fever and asthma but residual volume was clevatcd and E‘EV, diminished only in asthmatics. They concluded that asthmatics had both central and peripheral airway changes whereas those with hay fever reacted primarily with largcbr crntral airways. A. Kalisker, reporting for the National Asthma Center in Colorado, described technicalities of methodology developed for extending their studies relating to the lower accumulations of cA,MP in blood leukocytes from asthmatics when
VOLUME 55 NUMBER 6
Asthma
and Allergic
Disease
Centers
Workshop
375
the cells are incubated in vitro with catecholamines. Pre-exposure of monolayers enriched with B lymphocytes (60%) to catecholamines resulted in a specific, but reversible, desensitization to these agonists of the cells’ beta receptors linked to adenylate cyclase. In investigations of aspirin and tartrazine intolerance in asthmatic patients, J. Harnett, of the National Jewish Hospital in Colorado, stated that four fifths of patients with histories of ASA intolerance reacted with a 20% or greater fall in baseline FEV, on oral challenge to aspirin while one third of aspirin-intolerant asthmatics demonstrated a similar response on challenge to tartrazine. SESSION III. ACTION OF PHARMACOLOGIC POSSIBLE THERAPEUTIC EFFICACY
AGENTS OF
S. Spector, of the National Jewish Hospital of Denver, indicated that patients with severe chronic bronchial asthma tolerated aerosol treatment with triamcinolone acetonide well and most patients could be tapered from their baseline oral corticosteroids. However, if a patient were switched to a placebo aerosol, the beneficial effect of the active preparation appeared to “carry over” for almost two weeks. G. Cropp, of the National Asthma Center, has found that atropine and isoproterenol elicit significant and comparable improvements in all pulmonary functions, suggesting that a significant portion of airway obstruction in asthmatic children is parasympathetically mediated and can be atropine-blocked. The therapeutic effectiveness of a single dose of atropine sulfate aerosol was comparable to that of isoproterenol. These findings in children were supported by the experimental work of the Harvard group as reported by .J. Drazen, suggesting that secondary cholinergic effects are of major importance in mediating the response of the upper and central airways to antigen and to isolated mediators while the response of the remainder of the lung 6o these agents appears to be mostly direct in nature. Several Centers have been engaged in an evaluation of immunotherapeutic modalities. M. Valentine, of Johns Hopkins, presented additional evidence to confirm their belief that whole body extracts of Hymenoptera were inferior to venoms as diagnostic materials. The efficacy of venom therapy was demonstrated by a rise in blocking antibodies inhibiting leukocyte histamine release, a concomitant rise in IgG against venom proteins, and an associated clinical state of immunity to the systemic effects of deliberately induced stings. However, C. Arbesman, of SUNY, Buffalo, could not confirm t,he Hopkins findings, since his group found no significant differences between bee venom or whole bee body extracts on intradermal testing of bee-sensitive patients. An unusual finding in a few patients was that of negative RAST’s with bee venom or its fractions but positive RAST’s to whole bee body extracts. They also noted that for most patients, bee venom and phospholipase A had greater release of histamine and slow reacting substance of anaphylaxis (SRS-A) than did whole body extracts and that hyaluronidase may be an important component of bee venom.
376
Froehlich
J ALLERGY CLIN.
IMMUNOL. JUNE 1975
Preliminary data presented by R. Patterson, of Sorthweetcrn l’niveraity. 011 the immunologic activity of polymerized ragweed antigen I< in~li~~atrtl that this preparation could have considerable potential in ~~011~ imrnunot hcrapl.. 1t \ nnnpathogcnic orgarlisms contributing t0 the produe inn of the (liscasc! prnccss merits further investigation. Hefore ennrdinatctl calinical trials can b(b institutclcl, ;, necessary ltrcrquisite is the use l)y part ic*ipat ing invcstigatnrs 01’ stantlartl nomcnclaturc, rcbagtqita. methods, ant1 proc*ctlurc~s, in orclcr to ;Ichievc* c.nmparable results and data that can bc ponlcti. ;\ sta~ltl;lrcliz;ltic,rl committee (*hairo(l 1,~ Dr. Richard Farr, of the Sational .Icwish llospital ill I)c~vcI*, is preparing for publi(*atioll a rc~cnrnmended stanclard I)rotocol OII Ilronc*hinl inhalation chnllct~,uc*. itlc*ltlJing skin testing aIId alltarccnic c’st r;ic*t 11~0. New c*nniInittc>c5 wcr(’ f’ormct(l iit thct I;ist workshop : the SoIncn~li;t\~I*(~ (‘omrnittcc, to hts c*hairc>ll I1.v I )r (‘)l;lrlcns I(l, anti a IIynlcnoptcra sctlsitivity c*l)rlIInitteca that would address itself to the devc:l-
VOLUME 55 NUMBER 6
Asthma
and Allergic
Disease
Centers
Workshop
377
opment of standard materials for the skin testing and study of Hymenoptera-sensitive patients, to be chaired by Dr. Lawrence Lichtenstein. An event of interest at these workshops is a dinner meeting, during which a Washington-based government official speaks on Federal policies and statutes relevant to Center activities. This year’s speaker was Dr. Charles Lowe, Executive Director of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, who made a thoughtful analysis of the implications of Title II of the new National R.esearch Act, dealing with clinical investigations on human subjects.
M.D.
Helicesdu,
Xd.
The Asthma and Allergic Disease Centers Workshops, held at thcb National Institutes of Health and sponsored by the National Institute of Allerg?: and Infectious Diseases, arp an annual and eagerly anticipated cvcbnt for the Center program directors and their key staff. Thcsc. workshops provide a forum for free-flowing exchange of ideas, progress reports, discussion of mutual s&ntific and administrative problems pertinent to Center activities, and exploration of future possibilities for coordinated clinical trials. IIaving entered its fourth year. the program now can report substantial progress. 1.ndcr the cffcctivt chairmanship of Dr. K. Frank Austen, the participants of the most recent workshop provided material for an exciting and productive meeting. Some 72 scientists, representing various disciplines from 17 (Yetiters* in 13 of the IJnited States, gathered la& Deeember 5-6 in Bethesda to discuss their most recent findings in the study of allergic disorders. The discussions focua:d on three major topics. each the subject of a separate session. SESSION
I. lMMUUODERMATOLOOlC
D#QRDERS
I’. Kohler, of the IJniversity of Colorado, presented preliminary data on a series of patients with palpable purpura demonstrating nctrrotizing or leukocytoelastic vasculitis on skin biopsy. 1)cposition of immunoglobulins and C3 in vessel walls of both involved and uninvolved skin with frequent associated findings of cryoprotcins and histories of rrccAnt strcptococcal infection suggests that the illness is primarily the result of tissue damage mediated via immune complexes. A series of nonatopic females presenting with chronic refractory urticaria accompanied by arthralgias and elevated ~~rythrocyte sedimentation rates were studied by I. (:igli from Harvard. Skin biopsies indicate that this syndrome From the National lnstitutc of Allergy and Infectious Disease. Hecrivcd for publication Feb. 28, 1975. ‘Thr 17 Asthma and Allergic Disease Centers and their progrum directors are as follows: Robert B. Brighnm Hospital, Boston (Dr. K. Frank Au&en) ; Creighton University, Omaba (Dr. Robert R. Townley) ; Duke University Medical Center, Durham (Dr. Rebecca H. Buckley) .; The aood Samnritan Hospital, Baltimore (Dr. Philip 8. Norman) ; Louisiana State IJmoerdty, New Orleans (Dr. John Salv gio) ; Mayo Clinic and Foundation, Roeh. ester (Dr. Gerald J. Gleich) ; National Asthma 7 enter, Denver (Dr. Elliott Middleton, .7r.) ; National Jewish Hospital ond Research Center, Denver (Dr. Richard 9. Farr) ; Northwestern University, Chicago (Dr. Roy Patterson) ; Scrippe Clinic and Research Foundation, 1,s Jolla (Dr. John H. Vaughan) ; State University of Sew York, Buftalo (Dr. Carl 73. Arhesman) ; University of California, San Francisco (Dr. Oscar L. F’rick) ; University of Colorado, Denver (Dr. Henry N. Claman) ; University of Michigan Medical Center, Ann Arbor (Dr. Kenneth P. Ynthews) ; University of Wisconsin, 3iadison (Dr. Gharlas E. Reed) ; Waahington University, S1. Louis (Dr. Charles W. Parkor) ; and NIAID, Beth&a (Dr. Allen P. Kaplan). Vol. 55, No. 6, pp. 376-s??
VOLUME 55 NUMBER 6
Asthma
and Allergic
Disease
Centers
Workshop
373
may be a manifestation of underlying necrotixing angiitis with or without hyporomplementemia. In a study of mediator release in patients with cold urticaria, A. Kaplan, of NIAID, noted a rise in plasma histamine levels in all patients within 5 minutes after submersion. In some patients with cholinergic urticaria, histamine is released during exercise and many cases also had vibration-induced swelling. A relationship was suggested between cholincrgic nrticaria and familial vibratory angioedema. A possibility exists of another group of patients with vibration-negative cholinergic urticaria involving release of other mediators, such as serotonin. A. Kulczycki from St. Louis suggested that patients with cold urticaria may have an immunoglobulin with anti-IgE activity that is a cryoglobulin. He cautioned that donor serum be warmed before preparation for P-K testing. IgE levels studied by G. Gleich and his group at Mayo correlated with the extent of skin involvement but not with estimates of severity in patients with atopic dermatitis. IgE levels changed during the course of the disease without clear-cut patterns. Elevated IgE levels were demonstrated in a variety of inflammatory dermatoses. In a study of peripheral blood leukocyte and Iymphocyte CAMP metabolism, C. Parker, of Washington University, noted that in active atopic dermatitis and severe psoriasis alterations in adrenergic responsiveness occurred. In discussing this report, C. Reed, of Wisconsin, stated that resting levels of CAMP in epidermal slices were found by his group to be elevated and were further increased upon treatment with catecholamines over that seen in normal subjects. R. Buckley, of Duke, reported on extension of studies on patients manifesting the syndrome of dermatitis, extreme hyperimmunoglobulinemia E, undue susceptibility to staphylococcal and fungal infections, and marked delayed cutaneous anergy. No association between hyperimmunoglobulinemia E and HL-A specificity or haplotype was found. Observed anomalies of mixed leukocyte culture responsiveness taken together with abnormalities in immune responses to soluble antigens suggest that defects may exist in either the lymphocytes or in the macrophages of these patients. The identification of Clq, C3, and Factor B deposition in acantholytic areas of early oral and skin lesions in patients with pemphigus vulgaris, as well as deposition of IgG in intercellular substances of both pathologic and normal areas, was reported by R. E. Jordon of Mayo. Their studies suggest that immune complexes occur in both sera and blister fluids and that complement activation may play a role in the pathogenesis of pemphigus vulgaris. SESSION II. BIOCHEMICAL AND OF THE ATOPIC INDIVIDUAL
PHYSIOLOGIC
RESPONSES
0. Frick’s group from San Francisco, California were concerned with the possible role of cellular immunity in food allergy. Delayed-onset allergy was associated with negative skin tests, skin window eosinophilia, and antigeninduced histamine release from leukocytes. Utilizing the Clausen leukocyte inhibition factor test, positive findings with milk and corn were noted in two
374
Froehlich
1. ALLERGY
CLIN.
IMMUNOL. JUNE 1975
thirds of patients manifesting negative immediate and delayed skin tests and radioallergosorbent test (RAST). The possibility of ~llular immunt* reactions to foods in some patients with hypersensitivity is suggcqted hut does not provc~ a cause-effect relationship in the pathogenesis of this condition. Their investigations on nasal airway resistance mrasurctl from t,he slope of an oscill~copc tracing of transnasal pressure drop vs. na.sal air flow were disc*ussetl 1)~ K. Mathews, of the I!nivcrsity of Michigall. Th(a marked rcactivit) of the uos(l to csternal stimuli was cmphasizetl. \\‘hilc phcnylcphrinc gave iI J)rogressive dose-related decrease in nasal airway rcsistancth, isoprotercnol protlucctl incrcascs in some nonatopic and asymptomatic atopic sub.jtchts and failed to decrease rc>sistance in symptomatic atopic subjects. The stuclics of C. Parker, of \Vashington l!nivcrsity, on serum prostaglandiu levels in bronchial asthma suggest that the significantly higher J)rostaglandin F levels in asthmatics is presumably due to increased rclcarre from leukocytes OI platelets, with preliminary obstarvations indicating that both prostaglandin J*’ and prostaglandin E arc detec*tahlc in sputum. In a study of mediator-provoked bronchial challenges in asthmatic patirnt.s, n. Stevenson and C. Arroyavc, from Scripps, noted significant falls in complement activity in two thirds of patients with positive acroallergen challenges, with simultaneous activation of alternative pathway in some. In a selected group of asthmatic patients with evidence of rcaginica hypersensitivity, significant increases in histamine and lowered complement levels wcrc det.ectctl on13 during specific allergen bronchial challcngc and not during bronchospasm induced by methacholinc or during challenges against allergens to which no reaginic antibodies were identified. A system for grading mcthacholint~ dose-response curves in atopic. and nonatopic individuals has Hun developed hy R. Townlcy’s grouJ) from Creighton. Whereas former asthmatics, or asthmatics who have been in remission for longer than one year, fall into the high or medium categories of methacholine sensitivity and nonatopic individuals fall into negative categories, half of individuals with allergic rhinitis showed aI1 initial positive methacholinc inhalational response with a plateau J)hcnomenon in dose curves different from asthmatic patterns. This drop in FEV, remaining at a stable level despite additional methacholine inhalations suggested a feedback mechanism between heta adrenergic and cholinergic systems, interpreted to mean that these patients had sufficient intact beta adrenergic: receptors to counteract additional inhalations of methacholinc. R. Rosenthal, representing *Johns Hopkins, commented on their findings in which specific airway c*onductancc cahanges after inhalation challenge with mecholyl were similar in patients with hay fever and asthma but residual volume was clevatcd and E‘EV, diminished only in asthmatics. They concluded that asthmatics had both central and peripheral airway changes whereas those with hay fever reacted primarily with largcbr crntral airways. A. Kalisker, reporting for the National Asthma Center in Colorado, described technicalities of methodology developed for extending their studies relating to the lower accumulations of cA,MP in blood leukocytes from asthmatics when
VOLUME 55 NUMBER 6
Asthma
and Allergic
Disease
Centers
Workshop
375
the cells are incubated in vitro with catecholamines. Pre-exposure of monolayers enriched with B lymphocytes (60%) to catecholamines resulted in a specific, but reversible, desensitization to these agonists of the cells’ beta receptors linked to adenylate cyclase. In investigations of aspirin and tartrazine intolerance in asthmatic patients, J. Harnett, of the National Jewish Hospital in Colorado, stated that four fifths of patients with histories of ASA intolerance reacted with a 20% or greater fall in baseline FEV, on oral challenge to aspirin while one third of aspirin-intolerant asthmatics demonstrated a similar response on challenge to tartrazine. SESSION III. ACTION OF PHARMACOLOGIC POSSIBLE THERAPEUTIC EFFICACY
AGENTS OF
S. Spector, of the National Jewish Hospital of Denver, indicated that patients with severe chronic bronchial asthma tolerated aerosol treatment with triamcinolone acetonide well and most patients could be tapered from their baseline oral corticosteroids. However, if a patient were switched to a placebo aerosol, the beneficial effect of the active preparation appeared to “carry over” for almost two weeks. G. Cropp, of the National Asthma Center, has found that atropine and isoproterenol elicit significant and comparable improvements in all pulmonary functions, suggesting that a significant portion of airway obstruction in asthmatic children is parasympathetically mediated and can be atropine-blocked. The therapeutic effectiveness of a single dose of atropine sulfate aerosol was comparable to that of isoproterenol. These findings in children were supported by the experimental work of the Harvard group as reported by .J. Drazen, suggesting that secondary cholinergic effects are of major importance in mediating the response of the upper and central airways to antigen and to isolated mediators while the response of the remainder of the lung 6o these agents appears to be mostly direct in nature. Several Centers have been engaged in an evaluation of immunotherapeutic modalities. M. Valentine, of Johns Hopkins, presented additional evidence to confirm their belief that whole body extracts of Hymenoptera were inferior to venoms as diagnostic materials. The efficacy of venom therapy was demonstrated by a rise in blocking antibodies inhibiting leukocyte histamine release, a concomitant rise in IgG against venom proteins, and an associated clinical state of immunity to the systemic effects of deliberately induced stings. However, C. Arbesman, of SUNY, Buffalo, could not confirm t,he Hopkins findings, since his group found no significant differences between bee venom or whole bee body extracts on intradermal testing of bee-sensitive patients. An unusual finding in a few patients was that of negative RAST’s with bee venom or its fractions but positive RAST’s to whole bee body extracts. They also noted that for most patients, bee venom and phospholipase A had greater release of histamine and slow reacting substance of anaphylaxis (SRS-A) than did whole body extracts and that hyaluronidase may be an important component of bee venom.
376
Froehlich
J ALLERGY CLIN.
IMMUNOL. JUNE 1975
Preliminary data presented by R. Patterson, of Sorthweetcrn l’niveraity. 011 the immunologic activity of polymerized ragweed antigen I< in~li~~atrtl that this preparation could have considerable potential in ~~011~ imrnunot hcrapl.. 1t \ nnnpathogcnic orgarlisms contributing t0 the produe inn of the (liscasc! prnccss merits further investigation. Hefore ennrdinatctl calinical trials can b(b institutclcl, ;, necessary ltrcrquisite is the use l)y part ic*ipat ing invcstigatnrs 01’ stantlartl nomcnclaturc, rcbagtqita. methods, ant1 proc*ctlurc~s, in orclcr to ;Ichievc* c.nmparable results and data that can bc ponlcti. ;\ sta~ltl;lrcliz;ltic,rl committee (*hairo(l 1,~ Dr. Richard Farr, of the Sational .Icwish llospital ill I)c~vcI*, is preparing for publi(*atioll a rc~cnrnmended stanclard I)rotocol OII Ilronc*hinl inhalation chnllct~,uc*. itlc*ltlJing skin testing aIId alltarccnic c’st r;ic*t 11~0. New c*nniInittc>c5 wcr(’ f’ormct(l iit thct I;ist workshop : the SoIncn~li;t\~I*(~ (‘omrnittcc, to hts c*hairc>ll I1.v I )r (‘)l;lrlcns I(l, anti a IIynlcnoptcra sctlsitivity c*l)rlIInitteca that would address itself to the devc:l-
VOLUME 55 NUMBER 6
Asthma
and Allergic
Disease
Centers
Workshop
377
opment of standard materials for the skin testing and study of Hymenoptera-sensitive patients, to be chaired by Dr. Lawrence Lichtenstein. An event of interest at these workshops is a dinner meeting, during which a Washington-based government official speaks on Federal policies and statutes relevant to Center activities. This year’s speaker was Dr. Charles Lowe, Executive Director of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, who made a thoughtful analysis of the implications of Title II of the new National R.esearch Act, dealing with clinical investigations on human subjects.
