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Corticosteroids in Asthma* Rationale, Use, and Problems Paul A. Greenberger C or M.D., orticosteroids for patients inhaled are the experiencing in the presence asthma. of status maintenance roids into the Asthma Heart, of oral are very in hospitalized corticosteroids are patients permits by Blood the expert Institute, or with increased stimuli.” obstruction, mucus panel of the “is a lung treatment; airway with (2) airway over time, experience even disease remission, the is reeither of degree of bronchial and hypersecretion of either patient lasting months or permanently. For the acutely wheezing patient with asthma, it is preferable to administer an effective dosage of oral or systemic corticosteroids rather than to withhold them. For ambulatory torily with patients whose bronchodilators, asthma is not managed cromolyn, and avoidance ures in patients with IgE-mediated costeroids usually provide effective Indeed, in some effective antiasthma patients, asthma, control inhaled corticosteroids even if the A potent and The FOR administration duce the inhospital fatality tration of oral corticosteroids wise symptomatic emergency room desirable 8Fmm but for Division route noncompliant status cine, This Chicago requests: Avenue, Dr. Greenberger Chicago 60611 Allergy-Immunology, In the improvements Department School, Chicago. Northwestern University Medical study was supported by USPHS NIAID RR000048, and the Ernest S. Bazley Grant Memorial Hospital and Northwestern University. Reprint as a of administration patients.78 Both budesonide, adminisasthma, control supplemental was of terbutaline of patients responsiveness, a study and study with responsiveness with nate despite as compared groups had as mean differences the budesonide-treated reduced bronchial hyper- to terbutaline-treated patients.3 experienced bronchial lessened for which one explanation is enrollment in effective management of asthma. In another budesonide improved during 1 year of treatment, airway an average of fourfold as compared placebo-treated and triamcinolone patients.4 as well that although results corticosteroids, In addition as minimize in patients bronchial and help the need on morphologic patients the patients These grounds based with inhaled improve bronchial hyperresponsiveness to the empiric observations many reduce for other inhaled corticostecells in bronchial with asthma, but hyperresponsiveness.” clinically in asthma, dipropio- inhalation treatment in reduced suggest by with inflammatory Long-term resulted Beclomethasone acetonide wheezing mucus accumulation, lysosomal), persists. justifying use experimental Al 11403, to Northwestern grant East membrane suppression findings for if systemic 1 week of mucosal of sug- Other eral cytes, data effects and basophils, blood demonstrating cells have not their of corticosteroids and prevention of after allergen chalof the early bronchial Corticosteroids but (vascular and response blockage corticosteroids previously. mast stabilization of inflammation, the late bronchoconstrictive lenge. Some data support response of Medi- 303 agonists (and posbe more efficient can gest benefits that could rationalize their administration in the management of asthma. Corticosteroids have been associated with reduction of bronchial mucosal edema, avoid such provide for However, corticosteroids to the emergency asthmaticus, of Allergy-Immunology, re- adminisor other- helps corticosteroids, acetonide, essential some with asthma or recidivism at times helps from asthma. The to acutely wheezing administered or triamcinolone of patients the corticosteroids with treatment” of corticosteroids treatment rate patients room 6 Parenterally methylprednisolone less CORTICOSTEROIDS need in residual volume. During corticosteroids have been groups, after 2 years, did not have significantly responsiveness data of systemic reduced improve reductions newly diagnosed mild effective symptomatic hyperresponsiveness. between on biopsy RATIONALE demonstrate not yet improved. corticosteroid, with more biopsy specimens had not lost their monotherapy will significant patients compared to patients treated with inhaled terbutaline. Bronchial hyperresponsiveness to histamine, as measured by the provocative concentration to cause a 15% decline in FEY1, was 7.0 mg/ml in both groups initially. After 6 weeks, the budesonide-treated patients had reduced bronchial roids provide However, with beta-adrenergic respiratory effort FEy1 has inhaled medications. inhaled cortiof asthma. 6 to 12 h before residual capacity and hours after parenteral nocturnal satisfacmeas- require measurements administered along sibly theophylline), patients a variety the prednisone-requiring functional the initial rates be documented.’ and asthma inflammation; to flow can tered to patients associated with National disease responsiveness Asthma causes a variable airway inflammation, and far reduction characteristics: (1) airway obstruction that (but not completely so in some patients) (3) may therapeutic 20 to 60 mg adminisinhalation of corticoste- in stable as defined spontaneously and chest consymptoms the in expiratory changes clinically of oral corticosteroids. To address the use in asthma, this manuscript will be divided use, and problems. Lung, following versible maintenance corticosteroid asthmaticus dosages bronchi as While less and often consist of prednisone, tered on alternate days. Effective or discontinuation of corticosteroids into rationale, of asthma. wheezing, and other administered drugs Oral antiasthma valuable disabling dyspnea, controlled of systemically patients, effective exacerbations are to prevent wheezing of ineffectively high most corticosteroids pharmacotherapy striction, nocturnal dosages F.C.C.P been inhibit in vitro include administered proliferation mediator reduction release. of periph- presumably pulmonary eosinophils, lymphoand monocytes. There are experimental that 418$ Downloaded From: http://publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21648/ on 05/12/2017 corticosteroids Corticosteroids in vitro increase in Asthma (Paul A Greenberger) the actions of lipocortin, pholipase corticosteroids A2. contribute to increase major enzymes their (subsensitivity) USE OF administration for reversibility patients department who therapy, it nasal can be essential to In the inability to speak muscles of respiration corticosteroids a full or has necessary therapy. be There no data corticosteroid continued patients single to support doses such 6 h. The high-dose from several days have pulse, therapy the in- to 1 week greatly dose of prednisone, and can be ized patients most preserve integrity Sequence day prednisone should be of the of Hospitalization HPA should taken in to a axis. One be advised. the morning effective in the or conThe to Use of Corticosteroids After for Status Asthmaticus 1. Clear with parenteral or oral corticosteroids Convert to prednisone, 50 to 60mg each morning 3. Reexamine in 5 to 7 days after discharge; convert to prednisone, 50 mg, on alternate mornings and begin 2. inhaled corticosteroids’ 4. Decrease prednisone 5 to 10mg every 2 weeks if patient is stable 5. Daily prednisone course for increased respiratory symptoms or change in status 6. Discontinue prednisone if possible and continue inhaled corticosteroid 7. Administer stress corticosteroids and prednisone as pretreatment before future surgery ‘At this time, it is appropriate to discuss some corticosteroid side effects, alternative therapies, and benefits from effective control of asthma. An information sheet can be helpful. no of distribution in well-characterwill be as yet unknown. in the absence of asthma and For many patients, corticosteroids or even their is can of their the will perdiscontin- formulation a short in the effective dosage in daily help hospitaliza- adults and in days. beta-adrenergic provide satisfactory control of asthma in ambulatory As there is increasing emphasis on long-term use patients who it necessitates appropriate cough with asymptomatic will require such that inhaled drugs Failure to recognize such many mg can and weight for several combined with of inhaled corticosteroids, ness to teach and maintain Some respiratory of prednisone treatment to 60 g occasional of an upper course is 40 as 200 of beclomethasone experiences setting department 2 mg/kg of body corticosteroids corticosteroid actuation is not available as concentrated as the products. with asthma emergency The ng per is 6 times but usually infection, topical be administered 250 States marketed a patient children, Inhaled a potent countries, containing United prevent a strategy prednisone, of prednisone factors patient. A concentrated daily. agonists patients. version to alternate dose of prednisone In a pred- or elimination findings differences is incomplete Budesonide, in other exacerbations, short- patient has required long-term before the hospitalization, day differences triggering by the moderate is sufficient. required daily mI/mm/kg), These that with of volume of high-dose topical of oral corticosteroids of age. available and if the chest is clear and the patient is asymptomatic, decision can be made as to whether continued prednisone or not. If the corticosteroids (2.0 min).’4 suggest administration mit reduction tions. intermittent in terms clearance 210 consideration of potential avoidance acting corticosteroid. One method of use of corticosteroids is to discharge the patient recommending prednisone, 50 to 60 mg daily for 5 to 7 days. The patient should be examined is necessary days. reductions high dosages of inhaled agonists. Supplemental exacerbations of asthma alternate identified 11kg), currently When be converted an inexpensive, 0.6 life (about dipropionate 1,000 time tolerating were half twice of should at which vs patients years 4 administration as hydrocortisone, can be managed 1 week of daily prednisone of patients whose asthma differences (about and uation. In the United States, beclomethasone dipropionate or triamcinolone can be administered up to 16 to 20 times per day, and flunisolide, 8 times daily, in patients over 12 be given and is unknown. corticosteroids improved morning of to 300 mg, or methylprednisowith administration every prednisone, 50 mg, can the most effective dosage every of administered Effective asthma by pharmacodynainic Pharmacotherapy alone use a paradoxical with explained when a patient findings such to 6 h. Alternatively, repeated although mg of doses sentence, should cludes hydrocortisone, 200 lone, 40 to 50 mg intravenously treatment effective without further delay. Indeed, acute severe asthma and displays virtually corticosteroids, nisone to determine trial administer or larger considered 2 weeks day prednisone, and beta-adrenergic may be necessary during but usually comparison symptomatic patients, amto severe symptoms, and as every of alternate CownCosTERoIDs systemic are dosages to 50 to 60 mg on alternate tried. patients prednisone of acutely have mild prednisone can be reexamined of 5 to 10mg and have as a refractoriness themselves to the emergency improved with beta-adrenergic other the patient Most symptoms. oral The Corticosteroids have presented and have not flaring, with asthma.’ a diagnostic-therapeutic is to convert of phos- asthmaticus,’ accessory along action of respiratory corticosteroids presents with as in of corticosteroids from the perspective bulatory patients who a modality inhibit eicosanoid production by of phospholipase A2 could receptor number of beta-adrenergic status in of benefits beta-adrenergic role, the reversal The that A reduction via inhibition explanations corticosteroids. Oral and for inhaled bined need asthma and COPD to be determined. Despite the theophylline ance measures, sifled therapy be may may and basis only noncorticosteroid drugs. CHEST as with com- of each asthma, modality to for asthma, dreaded even on adverse effects. use of beta-adrenergic in addition to appropriate agonists, avoid- of asthma be provided When / 101 / 6 / JUNE, Downloaded From: http://publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21648/ on 05/12/2017 inhaled CORTICOSTEROIDS produce exacerbations cannot are be administered therapeutic be administered not with where the contributions Also in cough equivalent the widespread and cromolyn, that otherwise in patients trial REGARDING Corticosteroids a long-term but results corticosteroids of a diagnostic-therapeutic PROBLEMS inspiration perhaps 4 to 7 days of prednisone, can actually reach distal airways. “subclinical” asthma is one of the disappointing part corticosteroids may relieve symptoms. physician awareinhaler technique.’ may require by currently daily 1992 corticosteroids I Supplement intenavailable are 419$ and after ten years of treatment with inhaled steroids. Eur Respir J 1988; 1:883-89 12 Peers SH, Flower RJ. The role of lipocortin in corticosteroid actions. Am Rev Respir Dis 1990; 141:S18-S21 13 Fraser CM, Venter JC. Beta-adrenergic receptors: relationship of primary structure, receptor function, and regulation. Am Rev Respir Dis 1990; 141:S22-S30 14 Creenberger PA, Chow MJ, Atkinson AJ Jr, et al. Comparison of prednisolone kinetics in patients receiving daily or alternateday prednisone for asthma. Clin Pharmacol Ther 1986; 39:163- 15 Reed CE. Aerosol steroids as primary treatment of mild asthma. N Engl J Med 1991; 325:425-26 16 Fauci AS, Dale DC, Balow JE. Glucoeorticosteroid therapy: mechanisms of action and clinical considerations. Ann Intern Med 1976; 84:304-15 17 Spiro HM. Is the steroid ulcer a myth? N EngI J Med 1983; 309:45 18 Greenberger PA, Hendri 11W, Patterson R, et al. Bone studies in patients on prolonged systemic corticosteroid therapy for asthma. Clin Allergy 1982; 12:363-68 68 CHEST/lOl Downloaded From: http://publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21648/ on 05/12/2017 I 6 I JUNE, 1992 / Supplement 421S and after ten years of treatment with inhaled steroids. Eur Respir J 1988; 1:883-89 12 Peers SH, Flower RJ. The role of lipocortin in corticosteroid actions. Am Rev Respir Dis 1990; 141:S18-S21 13 Fraser CM, Venter JC. Beta-adrenergic receptors: relationship of primary structure, receptor function, and regulation. Am Rev Respir Dis 1990; 141:S22-S30 14 Creenberger PA, Chow MJ, Atkinson AJ Jr, et al. Comparison of prednisolone kinetics in patients receiving daily or alternateday prednisone for asthma. Clin Pharmacol Ther 1986; 39:163- 15 Reed CE. Aerosol steroids as primary treatment of mild asthma. N Engl J Med 1991; 325:425-26 16 Fauci AS, Dale DC, Balow JE. Glucoeorticosteroid therapy: mechanisms of action and clinical considerations. Ann Intern Med 1976; 84:304-15 17 Spiro HM. Is the steroid ulcer a myth? N EngI J Med 1983; 309:45 18 Greenberger PA, Hendri 11W, Patterson R, et al. Bone studies in patients on prolonged systemic corticosteroid therapy for asthma. Clin Allergy 1982; 12:363-68 68 CHEST/lOl Downloaded From: http://publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21648/ on 05/12/2017 I 6 I JUNE, 1992 / Supplement 421S