Humoral and celtular immunity in asthma D. I. Grove, T. 0. Burston, M. 1. Wellby, 1. J. Forbes Adelaide, Australia
R. Munro
Ford, and
Parameters of humor-al and cellular immunity have been measured in 91 asthmatic patients. Yenn s~rnrn levels of IgG and IgE were raised. IgG levels were higher k~ those with a family history of asthma. IgE levels were higher in those with a past history of atopic eczema, but intrinsic and extrinvic asthma could not be differentiated on the basis of IgE levels. Thirteen of 74 patients failed to respond to tetanus immunization, while only 1 failed to respond to Salmonella typhi H antigen. Tetanus nonresponders had a raised mean serum IgA level, I-e&cod spontaneous lymphocyte tritiated thy&dine uptake, and reduced thymidine uptake in fetal calf serum. Eight of 87 patients failed to mount delayed&hypersensitivity reactions to a battery of five intradermal antigens. The tritiated thymidine uptalce of lymphocytes stimulated with phytohemaggktinin was normal in antologows sernm, but reduced in fetal calf serum. The data support the hypothesis that asthma may 6e associated with immnnodeficiency states.
Leskowitz, Salvaggio, and Schwartz1 listed four hypotheses to account for the development of the, atopie state: (1) a predisposition of atopic persons to produce skin-sensitizing antibody on a hereditary basis, (2) a defect allowing prolonged retention of antigen with consequent heightened reaginie antibody production, (3) an enhanced reactivity to released pharmacologic intermediates, and (4) a defect in the defense barrier aeross mucosal surfaces with more e& cient contact between antigen and immunologically competent hells. There have also been suggestions that there may be an association between immunodefidency and atopy. Kaufman and Hobbs* have suggested that atopy develops in individuals whose immunologic memory is “backward” and demonstrated immunoglobulin deficiencies in an atopic population. A high prevalence of atopy has been noted in immunoglobulin deficiency syndromes.3 It has been suggested that transient IgA deficiency in infancy may be associated with the subsequent development of atopy.4 This study has been undertaken to measure various parameters of humoral and cellular immunity in asthma. The data support the hypothesis that asthma may be associated with a variety of immunodeficieney states, PATENTS
AND
CoN?lKtL
SlbEIlECTS
Forty-two male and 49 female asthmatic patients were studied. Their ages ranged from 9 to 63 years, with a mean age of 31 years. There was one patient in the first decade, and there were 18, 22, 29, 13, 6, and 2 patients in each sucProm the Department of Medicine, University of Adelaide, Department of Clinical Chemistry, Queen Elizabeth Hospital, and Royal Adelaide Hospital. Supported by the National Health and Medical Research Council of Australia. Received for publication Dec. 5, 1973. of Medicine, Queen Elizabeth Hospital, Reprint requests to: Dr. D. 1. Grove, Department Woodville, South Australia 5011. Vol. 55, No. 3, pp. 156-163
Humorol and cellular immunity in asthma
VOLUME 55 NUMBER 3
153
ceetling decade. There were unselected patients who consulted an allergist and agreed to take part in the study. Patients were considered to be asthmatic if they gave a history of intermittent wheezing and shortness of breath which resolved either spontaneously or on treatment with bronchotlilators.” Many patients had additional objective evidence of reversible airway obstruction on spirometry before and after inhalation of orciprenaline. It was dif?icult to demarcate clearly all patients as either intrinsic or extrinsic asthmatics; each patient was therefore classified into one of the following five groups on the basis of the clinical features and results of skin testing for immediate hypersensitivity and without knowledge of the other immunological findings. (I) Extrinsic: caused only by demonstrable allergens. ,Symptoms usually worse in spring and summer. All had positive skin tests. (2) dlosfly extrimic: as in (1) plus some wheezing aft.er colds or for no apparent reason. (3) ~xtri?lsic-iwtri~lsic: ev nly balanced (1) and (5). (4) J1ostZy i?l/e trinsic: as in (5) plus some incrimination of extrinsic factors. (5) Intrinsic: n0 demonstrable extrinsic cause, but wheezing frequently associated with respiratory infections, weather changes, emotion, exercise, often with a tendency for symptoms to be worse in winter. All had negative skin tests. Most patients were receiving some form of drug therapy both prior to and during the study. Fifty-one patients were receiving bronchodilators, either orally or by inhalation. Twenty-seven were taking antihistamines; 18, disodium cromoglycate, 20 to HOmg. daily; 12, antibiotics, mostly benzathine penicillin; 3, bromhexine; 1, amitriptyline; 1, diazepam. Thirty-one patients had been on a course of hyposensitizing injections, twice a week or more, for at least one month, with graded antigen preparations (Commonwealth Serum Laboratories, CSL) . The control values were established on normal people, together with a few patients suffering from vascular or neurologic diseases. Control patients were not receiving drug therapy. Xot all parameters were measured for each control subject. The mean age of the control population was 33.1 years, with age range and distribution similar to those of the asthmatic group. METHODS Patients were skin-tested for immediate hypersensitivity allergens and respiratory function assessed by spirometry.
lmmunoglobulin
responses
to a wide
range
of
levels
Serum levels of immunoglobulins (Ig) G, A, M, and D were measured with Behringwerke immunodiffusion plates. Standard solutions were obtained from Behringwerke. Serum levels of IgE were measured both by the radioactive single radial diffusion method described by Rowe6 and with the commercially available solid-phase radioimmunoassay “Phadebas IgE Test” (Pharmacia, Uppsala). A high correlation was obtained between the two methods (r = 0.9765, p < 0.001). lgE standard was from a batch of pooled human sera, 69/204, supplied by WHO.
Antibody
responses
Patients were immunized with tetanus toxoid (CSL), 0.5 ml. subcutaneously, and typhoid vaccine (CSL), 0.1 ml. subcutaneously, and blood was collected, usually at 2 weeks, but up to
154
Grove
J. ALLERGY CLIN. IMMUNOL. MARCH 1975
et al.
TABLE I. Serum
immunoglobulin
levels
kl*
I
TgG asthmatic patients Control subjects Igll asthmatic patients Control Puhjects IgM asthmatic patients Control subjects IgI) asthmatic subjects Control subjects IgI+; asthmatic patients Control sulljeets
No.
91 88 91 $7 91 x9
/
Mean
1,462 1,190 203 197 149s 14X$
/
S.D.
91
11.9$
47
74 91 100
16.9$ 2259 w
62 480 110
“IgG, IgR, and IgM in milligrams per 100 ml. IgD and IgE t Probability by Student’s t test. :s.s. : not significant. QGeomctric mean and standard deviation.
( Pi-obabliiy t
394 311 90 77 56 70
T of the reaginic system or relative inefficiency of the other humoral or cellular immune mechanisms. These two systems may each he subject to gcnctie influences. The great range ill sevt4t.y of clinical asthma may similarly rctlect the interaction of these factors. There may be many varieties of immunologic deficiency that have, as their common response, a clinical presentation as one of the atopic diseases. \vc wish to thank Mr. M. O’Halloran
for statistical
advice.
REFERENCES 1 Lcskowitz, S., Salvaggio, J. PI., and Schwartz, H. J.: An hypothesis for the development of atopic allergy in man, Clin. Allergy 2: 237, 1972. 2 Kaufman, H. S., and Hobbs, J. R.: Immunoglobulin deficiencies in an atopic population, Lancet 2: 1061, 1970. 3 Hobbs, .J. K.: ‘Primary immune paresis, in Adinolfl, M.: Bmnunolog~ and development, Clinics in Developmental Medicine. No. 34. London, 1969,,_Spastic Institute Medical Publi(:ittions, chap. 5, p. 114. 4 Taylor, H., Norman, A. P., Ogel, II. A., Stokes, C. B., Turner, M. W., and Soothill, J. F.: Transient IgA deficiency and pathogenesis of infantile atopy, Lancet 2: 111, 1973. 5 Readding, J. G.: Meaning of diabnostir terms in bronchopulmonary disease, Hr. Med. J. 2: 1425, 1963. 6 Rowe, 1). S.: Radionetive single radial diffusion, Rull. WHO 40: 613, 1969. 7 Forbes, 1. J.: Measurement of immunological function in clinical medicine, Aust. N. Z. .J. M(?d. 2: 160, 1971. 8 l)ixon, W. .J., and Massey, E. J., Jr.: introduction t,o statistical analysis, ed. 3, New York, 1969, McGraw-Hill Book Company, p. 243. ed. 1, London, 9 P:rradintr, C. J., and R.ivett, B. II. P.: Statistieal methods for technologists, 1960, English Universities Press, p. 112. 10 Ling, X. R.: Lymphocyte stimulation, Amsterdam, 1968, North Holland Publishing Company. 11 Field, El. J., and Caspary, E. A.: Inhibition of lymphocyte response by serum, Lancet 2: 95, 1971. 12 Kuhn?, W. +J., and Pappenheimer, A. M.: Immunochemical studies of antitoxin produced in normal and allergic with diphtheria toxoid, J. Exp. Med. 4: ., individuals hyperimmunized __ 363, 1952. 13 Salvaggio, J. E., Cavanaugh, J. J. A., Lowell, F. C., and Leskowitz, 8.: A comparison of the immunologic responses of normal and atopie individuals to intranasally administered antigen, J. AI.LF.RQY 35: 62, 1964. 14 Hess, M. W.: Experimental thymectomy, Berlin, Heidelberg, and New York, 196S, SpringerVerlag. 16 Davies, A. J. S., Carter, R. L., Leuchars, E., Wallis, V., and Dietrich, F. M.: The morphology of immune reactions in normal, thymectomized and reconstituted mice. II. Response to haeterial antigens: Salmonellar flagellar antigens and pneumococcal polysaccharide, lmmunology 19: 945, 1970. 16 Johansson, S. G. 0.: Raised levels of a new immunoglobulin class (TgND) in asthma, Lancet 2: 951, 1967. 17 Huntley, 1). C., Lyerly, A., and Winston-Salem, N. C.: Immune globulin determinations in allergic children, Am. J. Dis. Child. 106: 545, 1963. 18 Momma, K.: lmmunochemical and semiquantitative estimation of yM and yA immunoglobulins in healthy and diseased children, Acta Paediatr. Jap. 7: 1, 1965. 19 Buckley, B. H., Dees, 8. C., and O’Fallon, W. Y.: Serum immunoglobulins. I. Levels in normal children and in uncomplicated childhood allergy, Pediatrics 41: 606, f&X 20 Collins-Williams, C., Tkachgk, 5. J., Toft, B., Generosos, L., and Moeearello, M.: IgG, IgA and 1gM in children with intractable asthma, Ann. Allergy 25: 177, 1967.
VOLUME 55 NUMBER 3
Humoral
and cellular
immunity
in asthma
163
21 Kaufman, H. S., and Hobbs, J. R.: Immunoglobulin deficiencies in an atopic population, Lancet 2: 1061, 1970. 22 Kumar, L., Newcomb, R. W., and Hornbrook, M.: A year-round study of serum IgE levels in asthmatic children, J. ALLERGY48: 305, 1973. 23 Williams, 1). A.: Zn The nature of asthma, a symposium held at King Edward VII Hospital, Midhurst, 1964. 24 Rerg, T., and Johansson, S. G. 0.: IgE concentrations in children with atopic diseases, Int. Arch. Allergy 36: 219, 1969. 25 Rowe, 1). S., and Wood, C. 13. 5.: The measurement of serum IgE levels in healthy adults and children with allergic asthma, Int. Arch. Allergy 39: 1, 1970. 26 Henderson, L. I,., Swedlund, H. A., Van Dellen, R. G., Marcoux, J. P., Carryer, H. M., Peters, G. A., and Gleich, G. J.: Evaluation of IgE tests in an allergy practice, J. ALLERGY
48: 361, 1971. 27 Grove, D. l., and Forbes, J. J.: Increased
resistance to helminth infestation in an atopic population. In press, Med. J. Aust. responses of allergic and 28 Salvaggio, J., Kayman, H., and Leskowitz, S.: Immunologic normal subjects to pneumococcal polysacckaride, Int. Arch. Allergy 40: 520, 1971. 29 Schwartz, H. J., and Terr, A. I.: The immune response of allergic and normal subjects to pneumococcal polysaccharide, Int. Arch. Allergy 40: 520, 1971. 30 Greenert, S., Bernstein, I. L.! and Michael, J. G.: Immune responses of non-atopic individuals to prolonged immunization with ragweed extract, Lancet 2: 1121, 1971.
Select the Foundation Question
ONE best answer for the of America Self-Assessment 1. Pulmonary EXCEPT
emphysema
following Program:
is associated
question
with
from
the
Allergy
each of the following
(A) increased airway resistance due to hyperinflation of the lung (6) increased airway resistance that is irregularly distributed (C) airway resistance that is especially increased during expiration (D) increased lung volume (E) irregular distribution of the pulmonary blood flow The correct answer this Journal.
and bibliographic
reference
will
be found
on page
194 of
R. Munro
Ford, and
Parameters of humor-al and cellular immunity have been measured in 91 asthmatic patients. Yenn s~rnrn levels of IgG and IgE were raised. IgG levels were higher k~ those with a family history of asthma. IgE levels were higher in those with a past history of atopic eczema, but intrinsic and extrinvic asthma could not be differentiated on the basis of IgE levels. Thirteen of 74 patients failed to respond to tetanus immunization, while only 1 failed to respond to Salmonella typhi H antigen. Tetanus nonresponders had a raised mean serum IgA level, I-e&cod spontaneous lymphocyte tritiated thy&dine uptake, and reduced thymidine uptake in fetal calf serum. Eight of 87 patients failed to mount delayed&hypersensitivity reactions to a battery of five intradermal antigens. The tritiated thymidine uptalce of lymphocytes stimulated with phytohemaggktinin was normal in antologows sernm, but reduced in fetal calf serum. The data support the hypothesis that asthma may 6e associated with immnnodeficiency states.
Leskowitz, Salvaggio, and Schwartz1 listed four hypotheses to account for the development of the, atopie state: (1) a predisposition of atopic persons to produce skin-sensitizing antibody on a hereditary basis, (2) a defect allowing prolonged retention of antigen with consequent heightened reaginie antibody production, (3) an enhanced reactivity to released pharmacologic intermediates, and (4) a defect in the defense barrier aeross mucosal surfaces with more e& cient contact between antigen and immunologically competent hells. There have also been suggestions that there may be an association between immunodefidency and atopy. Kaufman and Hobbs* have suggested that atopy develops in individuals whose immunologic memory is “backward” and demonstrated immunoglobulin deficiencies in an atopic population. A high prevalence of atopy has been noted in immunoglobulin deficiency syndromes.3 It has been suggested that transient IgA deficiency in infancy may be associated with the subsequent development of atopy.4 This study has been undertaken to measure various parameters of humoral and cellular immunity in asthma. The data support the hypothesis that asthma may be associated with a variety of immunodeficieney states, PATENTS
AND
CoN?lKtL
SlbEIlECTS
Forty-two male and 49 female asthmatic patients were studied. Their ages ranged from 9 to 63 years, with a mean age of 31 years. There was one patient in the first decade, and there were 18, 22, 29, 13, 6, and 2 patients in each sucProm the Department of Medicine, University of Adelaide, Department of Clinical Chemistry, Queen Elizabeth Hospital, and Royal Adelaide Hospital. Supported by the National Health and Medical Research Council of Australia. Received for publication Dec. 5, 1973. of Medicine, Queen Elizabeth Hospital, Reprint requests to: Dr. D. 1. Grove, Department Woodville, South Australia 5011. Vol. 55, No. 3, pp. 156-163
Humorol and cellular immunity in asthma
VOLUME 55 NUMBER 3
153
ceetling decade. There were unselected patients who consulted an allergist and agreed to take part in the study. Patients were considered to be asthmatic if they gave a history of intermittent wheezing and shortness of breath which resolved either spontaneously or on treatment with bronchotlilators.” Many patients had additional objective evidence of reversible airway obstruction on spirometry before and after inhalation of orciprenaline. It was dif?icult to demarcate clearly all patients as either intrinsic or extrinsic asthmatics; each patient was therefore classified into one of the following five groups on the basis of the clinical features and results of skin testing for immediate hypersensitivity and without knowledge of the other immunological findings. (I) Extrinsic: caused only by demonstrable allergens. ,Symptoms usually worse in spring and summer. All had positive skin tests. (2) dlosfly extrimic: as in (1) plus some wheezing aft.er colds or for no apparent reason. (3) ~xtri?lsic-iwtri~lsic: ev nly balanced (1) and (5). (4) J1ostZy i?l/e trinsic: as in (5) plus some incrimination of extrinsic factors. (5) Intrinsic: n0 demonstrable extrinsic cause, but wheezing frequently associated with respiratory infections, weather changes, emotion, exercise, often with a tendency for symptoms to be worse in winter. All had negative skin tests. Most patients were receiving some form of drug therapy both prior to and during the study. Fifty-one patients were receiving bronchodilators, either orally or by inhalation. Twenty-seven were taking antihistamines; 18, disodium cromoglycate, 20 to HOmg. daily; 12, antibiotics, mostly benzathine penicillin; 3, bromhexine; 1, amitriptyline; 1, diazepam. Thirty-one patients had been on a course of hyposensitizing injections, twice a week or more, for at least one month, with graded antigen preparations (Commonwealth Serum Laboratories, CSL) . The control values were established on normal people, together with a few patients suffering from vascular or neurologic diseases. Control patients were not receiving drug therapy. Xot all parameters were measured for each control subject. The mean age of the control population was 33.1 years, with age range and distribution similar to those of the asthmatic group. METHODS Patients were skin-tested for immediate hypersensitivity allergens and respiratory function assessed by spirometry.
lmmunoglobulin
responses
to a wide
range
of
levels
Serum levels of immunoglobulins (Ig) G, A, M, and D were measured with Behringwerke immunodiffusion plates. Standard solutions were obtained from Behringwerke. Serum levels of IgE were measured both by the radioactive single radial diffusion method described by Rowe6 and with the commercially available solid-phase radioimmunoassay “Phadebas IgE Test” (Pharmacia, Uppsala). A high correlation was obtained between the two methods (r = 0.9765, p < 0.001). lgE standard was from a batch of pooled human sera, 69/204, supplied by WHO.
Antibody
responses
Patients were immunized with tetanus toxoid (CSL), 0.5 ml. subcutaneously, and typhoid vaccine (CSL), 0.1 ml. subcutaneously, and blood was collected, usually at 2 weeks, but up to
154
Grove
J. ALLERGY CLIN. IMMUNOL. MARCH 1975
et al.
TABLE I. Serum
immunoglobulin
levels
kl*
I
TgG asthmatic patients Control subjects Igll asthmatic patients Control Puhjects IgM asthmatic patients Control subjects IgI) asthmatic subjects Control subjects IgI+; asthmatic patients Control sulljeets
No.
91 88 91 $7 91 x9
/
Mean
1,462 1,190 203 197 149s 14X$
/
S.D.
91
11.9$
47
74 91 100
16.9$ 2259 w
62 480 110
“IgG, IgR, and IgM in milligrams per 100 ml. IgD and IgE t Probability by Student’s t test. :s.s. : not significant. QGeomctric mean and standard deviation.
( Pi-obabliiy t
394 311 90 77 56 70
T of the reaginic system or relative inefficiency of the other humoral or cellular immune mechanisms. These two systems may each he subject to gcnctie influences. The great range ill sevt4t.y of clinical asthma may similarly rctlect the interaction of these factors. There may be many varieties of immunologic deficiency that have, as their common response, a clinical presentation as one of the atopic diseases. \vc wish to thank Mr. M. O’Halloran
for statistical
advice.
REFERENCES 1 Lcskowitz, S., Salvaggio, J. PI., and Schwartz, H. J.: An hypothesis for the development of atopic allergy in man, Clin. Allergy 2: 237, 1972. 2 Kaufman, H. S., and Hobbs, J. R.: Immunoglobulin deficiencies in an atopic population, Lancet 2: 1061, 1970. 3 Hobbs, .J. K.: ‘Primary immune paresis, in Adinolfl, M.: Bmnunolog~ and development, Clinics in Developmental Medicine. No. 34. London, 1969,,_Spastic Institute Medical Publi(:ittions, chap. 5, p. 114. 4 Taylor, H., Norman, A. P., Ogel, II. A., Stokes, C. B., Turner, M. W., and Soothill, J. F.: Transient IgA deficiency and pathogenesis of infantile atopy, Lancet 2: 111, 1973. 5 Readding, J. G.: Meaning of diabnostir terms in bronchopulmonary disease, Hr. Med. J. 2: 1425, 1963. 6 Rowe, 1). S.: Radionetive single radial diffusion, Rull. WHO 40: 613, 1969. 7 Forbes, 1. J.: Measurement of immunological function in clinical medicine, Aust. N. Z. .J. M(?d. 2: 160, 1971. 8 l)ixon, W. .J., and Massey, E. J., Jr.: introduction t,o statistical analysis, ed. 3, New York, 1969, McGraw-Hill Book Company, p. 243. ed. 1, London, 9 P:rradintr, C. J., and R.ivett, B. II. P.: Statistieal methods for technologists, 1960, English Universities Press, p. 112. 10 Ling, X. R.: Lymphocyte stimulation, Amsterdam, 1968, North Holland Publishing Company. 11 Field, El. J., and Caspary, E. A.: Inhibition of lymphocyte response by serum, Lancet 2: 95, 1971. 12 Kuhn?, W. +J., and Pappenheimer, A. M.: Immunochemical studies of antitoxin produced in normal and allergic with diphtheria toxoid, J. Exp. Med. 4: ., individuals hyperimmunized __ 363, 1952. 13 Salvaggio, J. E., Cavanaugh, J. J. A., Lowell, F. C., and Leskowitz, 8.: A comparison of the immunologic responses of normal and atopie individuals to intranasally administered antigen, J. AI.LF.RQY 35: 62, 1964. 14 Hess, M. W.: Experimental thymectomy, Berlin, Heidelberg, and New York, 196S, SpringerVerlag. 16 Davies, A. J. S., Carter, R. L., Leuchars, E., Wallis, V., and Dietrich, F. M.: The morphology of immune reactions in normal, thymectomized and reconstituted mice. II. Response to haeterial antigens: Salmonellar flagellar antigens and pneumococcal polysaccharide, lmmunology 19: 945, 1970. 16 Johansson, S. G. 0.: Raised levels of a new immunoglobulin class (TgND) in asthma, Lancet 2: 951, 1967. 17 Huntley, 1). C., Lyerly, A., and Winston-Salem, N. C.: Immune globulin determinations in allergic children, Am. J. Dis. Child. 106: 545, 1963. 18 Momma, K.: lmmunochemical and semiquantitative estimation of yM and yA immunoglobulins in healthy and diseased children, Acta Paediatr. Jap. 7: 1, 1965. 19 Buckley, B. H., Dees, 8. C., and O’Fallon, W. Y.: Serum immunoglobulins. I. Levels in normal children and in uncomplicated childhood allergy, Pediatrics 41: 606, f&X 20 Collins-Williams, C., Tkachgk, 5. J., Toft, B., Generosos, L., and Moeearello, M.: IgG, IgA and 1gM in children with intractable asthma, Ann. Allergy 25: 177, 1967.
VOLUME 55 NUMBER 3
Humoral
and cellular
immunity
in asthma
163
21 Kaufman, H. S., and Hobbs, J. R.: Immunoglobulin deficiencies in an atopic population, Lancet 2: 1061, 1970. 22 Kumar, L., Newcomb, R. W., and Hornbrook, M.: A year-round study of serum IgE levels in asthmatic children, J. ALLERGY48: 305, 1973. 23 Williams, 1). A.: Zn The nature of asthma, a symposium held at King Edward VII Hospital, Midhurst, 1964. 24 Rerg, T., and Johansson, S. G. 0.: IgE concentrations in children with atopic diseases, Int. Arch. Allergy 36: 219, 1969. 25 Rowe, 1). S., and Wood, C. 13. 5.: The measurement of serum IgE levels in healthy adults and children with allergic asthma, Int. Arch. Allergy 39: 1, 1970. 26 Henderson, L. I,., Swedlund, H. A., Van Dellen, R. G., Marcoux, J. P., Carryer, H. M., Peters, G. A., and Gleich, G. J.: Evaluation of IgE tests in an allergy practice, J. ALLERGY
48: 361, 1971. 27 Grove, D. l., and Forbes, J. J.: Increased
resistance to helminth infestation in an atopic population. In press, Med. J. Aust. responses of allergic and 28 Salvaggio, J., Kayman, H., and Leskowitz, S.: Immunologic normal subjects to pneumococcal polysacckaride, Int. Arch. Allergy 40: 520, 1971. 29 Schwartz, H. J., and Terr, A. I.: The immune response of allergic and normal subjects to pneumococcal polysaccharide, Int. Arch. Allergy 40: 520, 1971. 30 Greenert, S., Bernstein, I. L.! and Michael, J. G.: Immune responses of non-atopic individuals to prolonged immunization with ragweed extract, Lancet 2: 1121, 1971.
Select the Foundation Question
ONE best answer for the of America Self-Assessment 1. Pulmonary EXCEPT
emphysema
following Program:
is associated
question
with
from
the
Allergy
each of the following
(A) increased airway resistance due to hyperinflation of the lung (6) increased airway resistance that is irregularly distributed (C) airway resistance that is especially increased during expiration (D) increased lung volume (E) irregular distribution of the pulmonary blood flow The correct answer this Journal.
and bibliographic
reference
will
be found
on page
194 of
