The consideration of immunotherapy in the treatment of allergic asthma Peter S. Creticos, MD  Journal of Allergy and Clinical Immunology  Volume 105, Issue 2, Pages S559-S574 (February 2000) DOI: 10.1016/S0091-6749(00)90060-5 Copyright © 2000 Mosby, Inc. Terms and Conditions

Fig. 1 Results of 24-hour samples from July 1 to Oct 1, 1980, for atmospheric ragweed (RW ) pollen counts, short ragweed (SRW ) allergenic activity, antigen E content, and average symptom scores of SRW-sensitive individuals (From Agarwal MK, Swanson MC, Reed CE, Yunginger JW. Immunochemical quantitation of airborne short ragweed, Alternaria, antigen E, and Alt-1 allergens: a two-year prospective study. J Allergy Clin Immunol 1983;74:40-5. By permission.) Journal of Allergy and Clinical Immunology 2000 105, S559-S574DOI: (10.1016/S0091-6749(00)90060-5) Copyright © 2000 Mosby, Inc. Terms and Conditions

Fig. 2 Schematic of allergic inflammation. LTs , Leukotrienes; Eos , eosinophil; Bas , basophil. (From Creticos PS. Peptide downregulation of the immune response. In: Marone G, Austen KF, Holgate ST, Kay AB, Lichtenstein LM, editors. Asthma and allergic diseases: physiology, immunopharmacology and treatment. San Diego (CA): Academic Press; 1998. p. 407-15. By permission.) Journal of Allergy and Clinical Immunology 2000 105, S559-S574DOI: (10.1016/S0091-6749(00)90060-5) Copyright © 2000 Mosby, Inc. Terms and Conditions

Fig. 3 Late-phase cellular responses after segmental airway challenge with saline solution and antigen in subjects with asthma. Control lavage was performed at the time of saline solution and antigen instillation into separate airway segments. After 17 to 22 hours, bronchoalveolar lavage was performed in challenged segments. Cells were enumerated by Giemsa-type and alcian blue stain, and total cells of each type were calculated on the basis of total cells recovered and differential enumeration. Antigen challenge increased total cell recovery (*P < .05), lymphocytes (Ly ; **P < .01), eosinophils (E ), alcian blue–positive cells (AB+ ), basophils, and indeterminate alcian blue–positive cells compared with control. A large neutrophil (N ) response was observed in both saline solution–challenged and antigen-challenged sites but was not significant because of large individual variability. Macrophages (Mac ) and bronchial epithelial cells (Br ) did not change. Increases in total lymphocytes, eosinophils, alcian blue–positive cells, basophils, and indeterminate alcian blue–positive cells were observed after antigen challenge compared with saline solution–challenged sites (ΔP < .05; ΔΔP < .01). The vast majority of alcian blue–positive cells (97%) were basophils. (From Liu MC, Hubbard WC, Proud D, et al. Immediate and late inflammatory responses to ragweed antigen challenge of the peripheral airways in allergic asthmatics. Am Rev Respir Dis 1991;144:51-8. © 1991 American Lung Association. Official Journal of the American Thoracic Society.) Journal of Allergy and Clinical Immunology 2000 105, S559-S574DOI: (10.1016/S0091-6749(00)90060-5) Copyright © 2000 Mosby, Inc. Terms and Conditions

Fig. 4 Allergen bronchial provocation with ragweed demonstrated a significant improvement in antigen sensitivity in the ragweed immunized group versus the placebo-injected subjects (P = .03). IT , immunotherapy. Journal of Allergy and Clinical Immunology 2000 105, S559-S574DOI: (10.1016/S0091-6749(00)90060-5) Copyright © 2000 Mosby, Inc. Terms and Conditions

Fig. 5 Bronchial inhalation challenge with cat-pelt extract. PD20 in FEV1 is indicated on vertical axis (log scale). Mean PD20-FEV1 for placebo-treated subjects was 294 and 56 breath units before and after therapy, respectively. This was not significant. Mean PD20-FEV1 for subjects who received cat-pelt extract was 51 and 2354 breath units before and after therapy (P < .01). (From Taylor WW, Ohman JL Jr, Lowell FC. Immunotherapy in cat-induced asthma: double-blind trial with evaluation of bronchial responses to cat allergen and histamine. J Allergy Clin Immunol 1978;61:283-7. By permission.) Journal of Allergy and Clinical Immunology 2000 105, S559-S574DOI: (10.1016/S0091-6749(00)90060-5) Copyright © 2000 Mosby, Inc. Terms and Conditions

Fig. 6 Changes in log PC20 for histamine in immunized and placebo-injected patients. (From Sundin B, Lilja G, Graff-Lonnevig V, et al. Immunotherapy with partially purified and standardized animal dander extracts. I. Clinical results from a double-blind study on patients with animal dander asthma. J Allergy Clin Immunol 1986;77:478-87. By permission.) Journal of Allergy and Clinical Immunology 2000 105, S559-S574DOI: (10.1016/S0091-6749(00)90060-5) Copyright © 2000 Mosby, Inc. Terms and Conditions

Fig. 7 Evolution of the provocative dose (PD ) eliciting a specific bronchial response before and after immunotherapy in 20 patients who had a rush protocol with a standardized Dp extract. Statistical analysis by Wilcoxon W -test. (From Bousquet J, Calvayrac P, Guerin B, et al. Immunotherapy with a standardized Dermatophagoides pteronyssinus extract. I. In vivo and in vitro parameters after a short course of treatment. J Allergy Clin Immunol 1985;76:734-44. By permission.) Journal of Allergy and Clinical Immunology 2000 105, S559-S574DOI: (10.1016/S0091-6749(00)90060-5) Copyright © 2000 Mosby, Inc. Terms and Conditions

Fig. 8 Total monthly emergency department (ER ) visits for asthma and rhinitis to the David Grant Medical Center compared with total monthly grass-pollen counts (GPCs ) from Jan 1981 to Dec 1984. Asthma visits correlated with GPC (r = 0.90 and P < .001). Rhinitis visits correlated with GPC (r = 0.92 and P < .001). (From Reid MJ, Moss RB, Hsu Y-P, et al. Seasonal asthma in northern California: allergic causes and efficacy of immunotherapy. J Allergy Clin Immunol 1986;78:590-600. By permission.) Journal of Allergy and Clinical Immunology 2000 105, S559-S574DOI: (10.1016/S0091-6749(00)90060-5) Copyright © 2000 Mosby, Inc. Terms and Conditions

Fig. 9 Evaluations of Asthma. Data from Baltimore, Md, have been shifted by 1 week to make the times of ragweed exposure coincide for the Baltimore, Md, and Rochester, Minn, areas. The brackets show the significance of the difference between the placebo and the immunotherapy groups in daily measurements or scores for the 3 weeks of the greatest pollen exposure, with the use of an analysis of variance to correct for differences during the observation phase. A , The weekly mean (± SE) peak expiratory flow rate (PEFR ) measured in the morning before, during, and after the ragweed-pollination season. Measurements of peak expiratory flow were recorded (with a mini peak flow meter) as the highest of 3 successive readings of peak flow when patients arose. B , The daily mean (± SE) medication scores for each week before, during, and after the ragweed-pollination season. Each of the following actions was scored as 1 unit: 200 mg of short-acting xanthine, 100 mg of long-acting xanthine, 1 puff from a sympathomimetic inhaler, a 2-mg albuterol tablet, a 2.5-mg terbutaline tablet, a 10-mg metaproterenol tablet, 1 puff of ipratropium, one half-puff of inhaled corticosteroid, 1 puff of a nasal corticosteroid, one half-puff of cromolyn, 0.5 mg of prednisone, and 0.4 mg of methylprednisolone. An injection of a bronchodilator was scored as 4 units, and respiratory therapy with a bronchodilator was scored as 4 units plus 1 unit for each 0.25 mL of medication. Antihistamines were not scored. C , The daily mean (± SE) asthma-symptom scores. Symptoms were scored on a 6-point scale: 0 = none; 1 = trivial or doubtful; 2 = mild and causing little or no discomfort; 3 = annoying but causing no marked discomfort; 4 = moderately severe and causing marked discomfort; 5 = severe and interfering with sleep or activities but not incapacitating; and 6 = incapacitating. (From Creticos PS, Reed CE, Norman PS, et al. Ragweed immunotherapy in adult asthma. N Engl J Med 1996;334:501-6. Copyright © 1996 Massachusetts Medical Society. All rights reserved.) Journal of Allergy and Clinical Immunology 2000 105, S559-S574DOI: (10.1016/S0091-6749(00)90060-5) Copyright © 2000 Mosby, Inc. Terms and Conditions