Clinical Reviews in Allergy

, Volume 3, Issue 2, pp 145–165 | Cite as

Late asthmatic responses: Inquiry into mechanisms and significance

  • W. James Metzger
  • Gary W. Hunninghake
  • Hal B. Richerson

Summary and Conclusions

Late asthmatic responses are common, simulate a chronic phase of asthma, and are associated with an influx of inflammatory cells. The precise sequence of events leading to late inflammatory responses and increased hyperrespon-siveness of the airways is uncertain, but likely begins with the triggering of mediator release from local (luminal or interstitial) mast cells or, conceivably, alveolar macrophages. Consequent influx and activation of granulocytes, including eosinophils and neutrophils, possibly T lymphocytes, basophils, and platelets, and subsequently later-arriving monocytes and macrophages, may be responsible for a continuing inflammatory reaction, airways hyperrespon-siveness, and continuing active bronchial asthma.

Identification of the relative importance of responsible cells and mediators will help clarify pathogenesis of bronchial asthma and should lead to a better understanding and design of therapeutic regimens and preventive measures in the management of this common and important disease.


Asthma Mast Cell Allergy Clin Immunol Occupational Asthma Bronchial Hyperresponsiveness 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Orehek J, Gayrard P, Smith AP, Grimaud C, Charpin J: Airway response to carbachol in normal and asthmatic subjects: Distinction between bronchial sensitivity and reactivity. Am Rev Respir Dis 115:937–943, 1977PubMedGoogle Scholar
  2. 2.
    Dolovich J, Hargreave F: The asthma syndrome: Inciters, inducers, and host characteristics (editorial). Thorax 36:641–644, 1981CrossRefGoogle Scholar
  3. 3.
    Industrial Injuries Advisory Council: Occupational Asthma. London, Her Majesty’s Stationery Office. 1981Google Scholar
  4. 4.
    Hendrick DJ, Fabbri L: Compensating occupational asthma. Thorax 36:881–884, 1981PubMedGoogle Scholar
  5. 5.
    Murphy RLH: Industrial diseases with asthma, in Weiss EG, Segal MS (eds): Bronchial Asthma: Mechanisms and Therapeutics. Boston, Little, Brown, 1976, pp 517–536Google Scholar
  6. 6.
    Chan-Yeung M, Lam S, Koener S: Clinical features and natural history of occupational asthma due to western red cedar (Thuja plicata). Am J Med 72:411–415, 1982PubMedCrossRefGoogle Scholar
  7. 7.
    Gleich GJ: The late phase of the immunoglobulin E-mediated reactions: A link between anaphylaxis and common allergic disease? J Allergy Clin Immunol 70:160–169, 1982PubMedCrossRefGoogle Scholar
  8. 8.
    Slavin RG, Fink JN, Becker RJ, Tennebaum JI, Feinberg SM: Delayed responses to antigen challenge in induced delayed reactivity: A clinical and cytologic study in man. J Allergy 35:499–505, 1964CrossRefGoogle Scholar
  9. 9.
    Green GR, Zweiman B, Beerman H, Hildreth EA: Delayed skin reactions to inhalant antigens. J Allergy 40:244–256, 1967CrossRefGoogle Scholar
  10. 10.
    Dolovich J, Hargreave FE, Chalmers R, Shier KJ, Gauldie J, Bienenstock J: Late cutaneous allergic responses in isolated IgE-dependent reactions. J Allergy Clin Immunol 52:38–46, 1973PubMedCrossRefGoogle Scholar
  11. 11.
    Solley GO, Gleich GJ, Jordon RE, Schroeter AL: The late phase of the immediate wheal and flare skin reaction: Its dependence upon IgE antibodies. J Clin Invest 58:408–420, 1976PubMedCrossRefGoogle Scholar
  12. 12.
    Taylor G, Shivalker PR: ‘Arthus-type’ reactivity in the nasal airways and skin in pollen sensitive subjects. Clin Allergy 1:407–414, 1971PubMedCrossRefGoogle Scholar
  13. 13.
    Dvoracek JE, Yunginger JW, Kern EB, Hyatt RE, Gleich GJ: Induction of nasal late-phase reactions by insufflation of ragweed-pollen extract. J Allergy Clin Immunol 73:363–378, 1984PubMedCrossRefGoogle Scholar
  14. 14.
    Herxheimer H: The late bronchial reaction to induced asthma. Int Arch Allergy Appl Immunol 3:323–328, 1952PubMedGoogle Scholar
  15. 15.
    Pepys J: Pulmonary aspergillosis, in Kallos P, Hasek M, Inderbitzin TM, Miescher PA, Waksman GH (eds): Monographs in Allergy, vol 4. Hypersensitivity Diseases of the Lungs Due to Fungi and Organic Dusts. Basel, S. Karger, 1969, pp 30–39Google Scholar
  16. 16.
    Pepys J: Introduction, in Kallos P, Hasek M, Inderbitzin TM, Miescher PA, Waksman BH (eds): Monographs in Allergy, vol 4. Hypersensitivity Diseases of the Lungs Due to Fungi and Organic Dusts. Basel, S. Karger, 1969, pp 11–19Google Scholar
  17. 17.
    Uhr JW, Salvin SB, Pappenheimer AM Jr: Delayed hypersensitivity II. Induction of hypersensitivity in guinea pigs by means of antigen-antibody complexes. J Exp Med 105:11–24, 1957PubMedCrossRefGoogle Scholar
  18. 18.
    Raffel S, Newel JM: The “delayed hypersensitivity” induced by antigen-antibody complexes. J Exp Med 108:823–841, 1958PubMedCrossRefGoogle Scholar
  19. 19.
    Richerson HB, Dvorak HF, Leskowitz S: Cutaneous basophilic hypersensitivity: A new interpretation of the Jones-Mote reaction. J Immunol 103:1431–1434, 1969PubMedGoogle Scholar
  20. 20.
    Richerson HB, Dvorak HF, Leskowitz S: Cutaneous basophil hypersensitivity. I. A new look at the Jones-Mote reaction, general characteristics. J Exp Med 132:546–557, 1970PubMedCrossRefGoogle Scholar
  21. 21.
    Dvorak HF, Dvorak AM, Simpson BA, Richerson HB, Leskowitz S, Karnovsky MJ: Cutaneous basophil hypersensitivity. II. A light and electron microscopic description. J Exp Med 132:558–582, 1970PubMedCrossRefGoogle Scholar
  22. 22.
    Richerson HB: Cutaneous basophil (Jones-Mote) hypersensitivity after “tolerogenic” doses of intravenous ovalbumin in the guinea pig. J Exp Med 132:630–641, 1971CrossRefGoogle Scholar
  23. 23.
    Richerson HB, Rajtora DW, Penick GD, Dick FR, Yoo TJ, Kammermeyer JK, Anuras JS: Cutaneous and nasal allergic responses in ragweed hay fever: Lack of clinical and histopathologic correlations with late phase reactions. J Allergy Clin Immunol 64:67–77, 1979PubMedCrossRefGoogle Scholar
  24. 24.
    Dvorak HF, Mihm MC Jr: Basophilic leukocytes in allergic contact dermatitis. J Exp Med 135:235–254, 1972PubMedCrossRefGoogle Scholar
  25. 25.
    Askenase PW: Cutaneous basophil hypersensitivity in contact-sensitized guinea pigs. I. Transfer with immune serum. J Exp Med 138:1144–1155, 1973PubMedCrossRefGoogle Scholar
  26. 26.
    Van Loveren H, Meade R, Askenase PW: An early component of delayed-type hypersensitivity mediated by T cells and mast cells. J Exp Med 157:1604–1617, 1983PubMedCrossRefGoogle Scholar
  27. 27.
    Felarca AB, Lowell FC: The accumulation of eosinophils and basophils at skin sites as related to intensity of skin reactivity and symptoms in atopic disease. J Allergy Clin Immunol 48:125–133, 1971PubMedCrossRefGoogle Scholar
  28. 28.
    Schleimer RP, MacGlashan DW Jr, Schulman ES, Peters SP, Adams GK, III, Adkinson NF, Jr, Lichtenstein LM: Human mast cells and basophils—Structure, function, pharmacology, and biochemistry. Clin Rev Allergy 1:327–341, 1983PubMedGoogle Scholar
  29. 29.
    Patterson R, Tomita Y, Oh SH, Suszko IM, Pruzansky JJ: Respiratory mast cells and basophiloid cells: I. Evidence that they are secreted into the bronchial lumen, morphology, degranulation and histamine release. Clin Exp Immunol 16:223–233, 1974Google Scholar
  30. 30.
    Kimura I, Tanizaki Y, Saito K, Takahashi K, Veda N, Sato S: Appearance of basophils in the sputum of patients with bronchial asthma. Clin Allergy 5:95–98, 1975PubMedCrossRefGoogle Scholar
  31. 31.
    Hirsch SR, Kalbileisch JH: Circulating basophils in normal subjects and in subjects with hay fever. J Allergy Clin Immunol 58:676–682, 1976PubMedCrossRefGoogle Scholar
  32. 32.
    Nagy L, Lee TH, Kay AB: Neutrophil chemotactic activity in antigen-induced late asthmatic reactions. N Engl J Med 306:497–501, 1982PubMedGoogle Scholar
  33. 33.
    Lee TH, Nagy L, Nagakura T, Walport MJ, Koy AB: Identification and partial characterization of an exercise-induced neutrophil chemotactic factor in bronchial asthma. J Clin Invest 69:889–899, 1982PubMedCrossRefGoogle Scholar
  34. 34.
    Cartier A, Thomson NC, Frith PA, Roberts R, Tech M, Hargreave FE: Allergen-induced increase in bronchial responsiveness to histamine: Relationship to the late asthmatic response and change in airway caliber. J Allergy Clin Immunol 70:170–177, 1982PubMedCrossRefGoogle Scholar
  35. 35.
    Boushey HA, Holtzman MJ, Sheller JR, Nadel JA: State of the art: Bronchial hyperreactivity. Am Rev Respir Dis 121:389–413, 1980PubMedGoogle Scholar
  36. 36.
    Richardson JB: Nonadrenergic inhibitory innervation of the lung. Lung 159:315–322, 1981PubMedCrossRefGoogle Scholar
  37. 37.
    Lam S, Wong R, Yeung M: Nonspecific bronchial reactivity in occupational asthma. J Allergy Clin Immunol 63:28–34, 1979PubMedCrossRefGoogle Scholar
  38. 38.
    Kaliner M, Shelhamer JH, Davis PB, Smith LJ, Venter JC: Autonomic nervous system abnormalities and allergy. Ann Intern Med 96:349–357, 1982PubMedGoogle Scholar
  39. 39.
    Szentivanyi A: The radioligand binding approach in the study of lymphocyte adrenoreceptors and the constitutional basis of atopy. J Allergy Clin Immunol 65:5–11, 1980PubMedCrossRefGoogle Scholar
  40. 40.
    Patterson R, Zeiss CR, Harris KE: Immunologic studies in experimental animals of occupational chemical antigens. Clin Immunol Allerg 4:159–172, 1984Google Scholar
  41. 41.
    Stanworth DR: Allergen structure and function, in: Immediate Hypersensitivity: The Molecular Basis of the Allergic Response. New York, American Elsevier, 1973, pp 167–179Google Scholar
  42. 42.
    Bronsky EA, Ellis EF: Inhalation bronchial challenge testing in asthmatic children. Pediatr Clin North Am 16:85–93, 1969PubMedGoogle Scholar
  43. 43.
    Ishizaka K, Ishizaka T: Immunology of IgE-mediated hypersensitivity, in Middleton E Jr, Reed CE, Ellis EF (eds): Allergy—Principles and Practice. St. Louis, C.V. Mosby, 1983, pp 52–78Google Scholar
  44. 44.
    Gwynn CM, Ingram J, Almousawi T, Stanworth DR: Bronchial provocation tests in atopic patients with allergen-specific IgG4 antibodies. Lancet 1:254–256, 1982PubMedCrossRefGoogle Scholar
  45. 45.
    Morley J, Hanson JM, Page CP: Mediator characterisation and asthma. Lancet 1:162, 1984PubMedCrossRefGoogle Scholar
  46. 46.
    Kulczycki A: Role of immunoglobulin E and immunoglobulin E receptors in bronchial asthma. J Allergy Clin Immunol 68:5–14, 1981PubMedCrossRefGoogle Scholar
  47. 47.
    Middleton E, Atkins FD, Fanning M, Georgitis JW: Cellular mechanisms in the pathogenesis and pathophysiology of asthma. Med Clin North Am 65:1013–1031, 1981PubMedGoogle Scholar
  48. 48.
    Pearce FL, Befus AD, Gauldie J, Bienenstock J: Mucosal mast cells. II. Effects of anti-allergic compounds on histamine secretion by isolated intestinal mast cells. J Immunol 128:2481–2486, 1982PubMedGoogle Scholar
  49. 49.
    Lewis RA, Austen KF: The biologically active leukotrienes. J Clin Invest 73:889–897, 1984PubMedCrossRefGoogle Scholar
  50. 50.
    Weissmann G: The Eicosanoids of asthma. N Engl J Med 308:454–456, 1983PubMedGoogle Scholar
  51. 51.
    Smith LF, Patterson R, Greenberger P, Krell R, Bernstein P: Airway response to inhaled leukotriene D4 in man. Am Rev Respir Dis 129(part 2):A1, 1984Google Scholar
  52. 52.
    Holroyde MC, Altounyan REC, Cole M, Dixon M, Elliott EV: Bronchoconstriction produced in man by leukotrienes C and D. Lancet 2:17–18, 1981PubMedCrossRefGoogle Scholar
  53. 53.
    Griffin M, Weiss JW, Leitch AG, McFadden ER Jr, Corey EJ, Austen KF, Drazen JM: Effects of leukiotriene D on the airways in asthma. N Engl J Med 308:436–439, 1983PubMedGoogle Scholar
  54. 54.
    Hansson G, Bjorck T, Dahlen SE, Hedqvist P, Granstrom E, Dahlen B: Specific allergen induces contraction of bronchi and formation of leukotrienes C4, D4, and E4 in human asthmatic lung, in Samuelsson B, Paoletti R, Ramwell P (eds): Advances in Prostaglandin, Thromboxane, and Leukotriene Research, vol 12. New York, Raven, 1983, pp 153–159Google Scholar
  55. 55.
    Knauer KA, Lichtenstein LM, Adkinson NF, Fish JE. Platelet activation during antigen-induced airway reactions in asthmatic subjects. N Engl J Med 304:1404–1407, 1981PubMedGoogle Scholar
  56. 56.
    Butterfield JH, Maddox DE, Gleich GJ: The eosinophil leukocyte: Maturation and function. Clin Immunol Rev 2:187–306, 1983–84PubMedGoogle Scholar
  57. 57.
    Frigas E, Loegering DA, Solley GO, Farrow GM, Gleich GJ: Elevated levels of the eosinophil granule major basic protein in the sputum of patients with bronchial asthma. Mayo Clinic Proc 56:345–353, 1981Google Scholar
  58. 58.
    Kaliner MM: Hypotheses on the contribution of late-phase allergic responses to the understanding and treatment of allergic diseases. J Allergy Clin Immunol 73:311–315, 1984CrossRefGoogle Scholar
  59. 59.
    Capron M, Spiegelberg HL, Prin L, Bennich H, Butterworth AE, Pierce RJ, Ouaissi MA, Capron A: Role of IgE receptors in effector fraction of human eosinophils. J Immunol 132:462–468, 1984PubMedGoogle Scholar
  60. 60.
    Weller PF, Lee CW, Foster DW, Corey EJ, Austen KF, Lewis RA: Generation and metabolism of 5-lipoxygenase pathway leukotrienes by human eosinophils: Predominant production of leukotriene C4. Proc Natl Acad Sri USA 80:7626–7630, 1983CrossRefGoogle Scholar
  61. 61.
    O’Flaherty JT, Wykle RL: Biology and biochemistry of platelet-activating factor. Clin Rev Allergy 1:353–367, 1983PubMedGoogle Scholar
  62. 62.
    Arnoux B, Duval D, Benveniste J: Release of platelet-activating factor (PAF-acether) from alveolar macrophages by calcium ionophore A23187 and phagocytosis. Eur J Clin Invest 10:437–441, 1980PubMedCrossRefGoogle Scholar
  63. 63.
    Brindley LL, Sweet JM, Goetzl EJ: Stimulation of histamine release from human basophils by human platelet Factor 4. J Clin Invest 72:1218–1223, 1983PubMedCrossRefGoogle Scholar
  64. 64.
    Nash AA, Gell PGH: The delayed hypersensitivity T cell and its interaction with other T cells. Immunol Today 2:162–165, 1981CrossRefGoogle Scholar
  65. 65.
    Bianchi ATJ, Hooijkass H, Benner R, Tees R, Nordin AA, Schreier MH: Clones of helper T cells mediate antigen-specific H-2-restricted DTH. Nature 290:62–63, 1981PubMedCrossRefGoogle Scholar
  66. 66.
    Dvorak HF, Mihm MC Jr, Dvorak AM, Johnson RA, Manseau EJ, Morgan E, Colvin KB: Morphology of delayed type hypersensitivity reactions in man. I. Quantitative description of the inflammatory response. Lab Invest 31:111–130, 1974PubMedGoogle Scholar
  67. 67.
    deShazo RD, Levinson AI, Dvorak HF, Davis RW: The late phase skin reaction. Evidence for activation of the coagulation system in an IgE dependent reaction in man. J Immunol 122:692–698, 1979PubMedGoogle Scholar
  68. 68.
    deShazo RD, Levinson AI, Dvorak HF: The late phase skin reaction: Paradigm or epiphenomena? Ann Allergy 51:166–172, 1983PubMedGoogle Scholar
  69. 69.
    Askenase PW, Van Loveren H: Delayed-type hypersensitivity: Activation of mast cells by antigen-specific T-cell factors initiates the cascade of cellular interactions. Immunol Today 4:259–264, 1983CrossRefGoogle Scholar
  70. 70.
    Sedgwick JD, Holt PG, Turner KJ: Production of a histamine-releasing lymphokine by antigen-or mitogen-stimulated human peripheral T cells. Clin Exp Immunol 45:409–418, 1981PubMedGoogle Scholar
  71. 71.
    Cohn ZA: The macrophage-versatile element of inflammation, in Harvey Society of New York (ed): The Harvey Lectures 1981–82. Orlando, FL, Academic, 1983, pp 63–80Google Scholar
  72. 72.
    Metzger WJ, Lakin R, Richerson HB, Monick M, Brady M, Worden K, Hunninghake GW: Bronchoalveolar lavage of allergic asthmatic patients following allergen bronchoprovocation: Methodology and observations. J Allergy Clin Immunol (submitted for publication)Google Scholar
  73. 73.
    Cade JF, Clancy RL, Walker SE, Pain MCF: Slow-reacting substance from alveolar macrophages—A mechanism of asthma? AJEBAK 59:449–454, 1981PubMedGoogle Scholar
  74. 74.
    Rankin JA, Hitchcock M, Merrill, WW, Huang SS, Brashler JR, Bach MK, Askenase PW: IgE immune complexes induce immediate and prolonged release of leukotriene C4 (LTC4) from rat alveolar macrophages. J Immunol 132:1993–1999, 1984PubMedGoogle Scholar
  75. 75.
    Melewicz FM, Kline LE, Cohen AB, Spiegelberg HL: Characterization of Fc receptors for IgE on human alveolar macrophages. Clin Exp Immunol 49:364–370, 1982PubMedGoogle Scholar
  76. 76.
    Melewicz FM, Zeiger RS, Mellon MH, O’Connor RD, Spiegelberg HL: Increased peripheral blood monocytes with Fc receptors for IgE in patients with severe allergic disorders. J Immunol 126:1592–1595, 1981PubMedGoogle Scholar
  77. 77.
    Godard P, Chaintreuil J, Damon M, Coupe Marlene, Flandre O, de Paulet AC, Michel FB: Functional assessment of alveolar macrophages: Comparison of cells from asthmatics and normal subjects. J Allergy Clin Immunol 70:88–93, 1982PubMedCrossRefGoogle Scholar
  78. 78.
    Joseph M, Tonnel AB, Torpier G, Capron A: Involvement of immunoglobulin E in the secretory processes of alveolar macrophages from asthmatic patients. J Clin Invest 71:221–230, 1983PubMedCrossRefGoogle Scholar
  79. 79.
    Martin TR, Altman LC, Albert RK, Henderson WR: Leukotriene B4 production by the human alveolar macrophages: A potential mechanisms for amplifying inflammation in the lung. Am Rev Respir Dis 129:106–111, 1984PubMedGoogle Scholar
  80. 80.
    Czarnetzki BM, Figdor CG, Kolde G, Vroom T, Aalberse R, de Vries JE: Development of human connective tissue mast cells from purified blood monocytes. Immunology 51:549–554, 1984PubMedGoogle Scholar
  81. 81.
    Dvorak AM, Dvorak HE, Peters SP, Shulman ES, MacGlashan DW Jr, Pyne K, Harvey VS, Galli SJ, Lichtenstein LM: Lipid bodies: Cytoplasmic organelles important to arachidonate metabolism in macrophages and mast cells. J Immunol 131:2965–2976, 1983PubMedGoogle Scholar
  82. 82.
    Metzger WJ, Nugent K, Richerson HB: Site of airway obstruction in allergen-induced late phase asthmatic responses. Chest (submitted for publication)Google Scholar
  83. 83.
    Metzger WJ, Dorminey HC, Robbins D, Richerson HB: Late asthmatic responses (LAR) during allergen bronchoprovocation (BPC). Correlation with specific IgE and symptoms. American Academy of Allergy and Immunology, 1981 (abstr)Google Scholar
  84. 84.
    Metzger WJ, Wasserman SI, Richerson HB, Donnelly A: Evidence for release of eosinophil and neutrophil chemotactic factors during early and late asthmatic responses. Clin Res 31:165, 1983Google Scholar
  85. 85.
    Wasserman SI, Austen KF, Soter NA: The functional and physiochemical characterization of three eosinophilotactic activities released into the circulation by cold challenge of patients with cold urticaria. Clin Exp Immunol 47:570–578, 1982PubMedGoogle Scholar
  86. 86.
    Kaplan AP: Urticaria and angioedema, in Middleton E, Reed CE, Ellis EF (eds): Allergy: Principles and Practice Vol II (ed 2). St. Louis, C.V. Mosby, 1983, pp 1341–1360Google Scholar
  87. 87.
    Kopeloff N, Kopeloff LM: Blood platelets in anaphylaxis. J Immunol 40:471–481, 1941Google Scholar
  88. 88.
    Metzger WJ, Henriksen RA, Zaleski T, Donnelly A: Evidence for platelet release and thrombin generation in early and late asthmatic responses. Clin Res 31:164, 1983Google Scholar
  89. 89.
    MacIntyre D, Boyd G: Site of airflow obstruction in immediate and late reactions to bronchial challenge withDermatophagoides pteronyssinus. Clin Allergy 13:213–219, 1983PubMedCrossRefGoogle Scholar
  90. 90.
    Metzger WJ, Nugent K, Richerson HB, Moseley P, Lakin R, Zavala D, Hunninghake GW: Methods for bronchoalveolar lavage in asthmatic patients following bronchoprovocation and local antigen challenge. Chest 87:16s-19s, 1985PubMedCrossRefGoogle Scholar
  91. 91.
    Worden K, Metzger WJ, Kopp W, Richerson HB, Hunninghake GW: Dissolution of eosinophil granules in bronchial lavage obtained from allergic asthmatics during bronchoprovocation and seasonal exposure. Proc Ann EMSA 41:798–799, 1983Google Scholar
  92. 92.
    Gerblich AA, Campbell AE, Schuyler MR: Changes in T-lymphocyte subpopulations after antigenic bronchial provocation in asthmatics. N Engl J Med 310:1349–1352, 1984PubMedCrossRefGoogle Scholar
  93. 93.
    Warner JO, Soothill JF, Price JF, Hey EN: Controlled trial of hyposensitization toDermatophagoides pteronyssinus in children with asthma. Lancet 2:912–915, 1978PubMedCrossRefGoogle Scholar
  94. 94.
    Platts-Mills TAE, Tovey ER, Mitchell EB, Moszow H, Nock P, Wilkins SR: Reduction of bronchial hyperreactivity during prolonged allergen avoidance. Lancet 2:675–678, 1982PubMedCrossRefGoogle Scholar
  95. 95.
    Behrens BL, March WR, Henson GL: Passive transfer of the late pulmonary response in an animal model-Relationship of immunologic status to pulmonary physiologic changes. Am Rev Respir Dis 127:65, 1983Google Scholar
  96. 96.
    Smith JA, Mansfield LE, deShazo RD, Nelson HS: An evaluation of the pharmacologic inhibition of the immediate and late cutaneous reaction to allergen. J Allergy Clin Immunol 65:118–121, 1980CrossRefGoogle Scholar
  97. 97.
    Stokes TC, Morley J: Prospects for an oral intal. Br J Dis Chest 75:1–14, 1981PubMedCrossRefGoogle Scholar
  98. 98.
    Bernstein IL: Cromolyn sodium in the treatment of asthma: Changing concepts. J Allergy Clin Immunol 68:247–253, 1981PubMedCrossRefGoogle Scholar
  99. 99.
    Prausnitz C, Küstner H: Studien über ueberempfind lichkeit. Zentralbl Bakteriol 86:160, 1921Google Scholar

Copyright information

© Humana Press Inc. 1985

Authors and Affiliations

  • W. James Metzger
    • 1
    • 2
  • Gary W. Hunninghake
    • 1
  • Hal B. Richerson
    • 1
  1. 1.From the University of Iowa College of MedicineIowa City
  2. 2.East Carolina University, School of MedicineGreenville

Personalised recommendations