2005, Number 1
<< Back Next >>
Rev Inst Nal Enf Resp Mex 2005; 18 (1)
Effect of rhDnase on irreversible bronchial obstruction in severe adult asthma
Vargas MH, Torre-Bouscoulet L, Salas-Hernández J, Furuya MEY
Language: Spanish
References: 39
Page: 14-21
PDF size: 87.85 Kb.
ABSTRACT
Background: In some asthma patients airway obstruction can not be reverted by bronchodilator and/or corticosteroid treatment. This irreversible obstruction has been attributed to the remodeling process of airways, but other mechanisms such as mucus plugging have not been explored.
Objective: To evaluate if rhDNase, an enzyme extensively used to fluidize the mucus in cystic fibrosis, improves spirometric variables and quality of life of asthmatic patients.
Patients and methods: Ten adult patients (6 females) with severe corticosteroid-dependent asthma received daily nebulizations of 2.5 mg rhDNase during 14-28 days. Spirometries were performed at least at weekly intervals to evaluate the forced vital capacity (FVC), forced expiratory flow at the first second (FEV1), the FEV1/FVC ratio and peak expiratory flow (PEF). Changes in spirometric variables were assessed by regression analysis. An asthma quality of life questionnaire was applied before and at the end of treatment.
Results: Spirometric variables did not change in most patients. However, pulmonary function improved in one patient, according to the statistically significant ascending slopes in FVC, FEV1 and FEV1/FVC. Although other subjects also had ascending (2 patients) or descending (2 patients) slopes, these changes only occurred in one spirometric variable. As a group, there was a trend for improvement in quality of life.
Conclusions: Although rhDNase does not modify the irreversible bronchial obstruction in most patients with severe asthma, a small proportion of them might obtain some beneficial effect.
REFERENCES
Cade J, Pain M. Pulmonary function during clinical remission of asthma. How reversible is asthma? Aust NZ J Med 1973;3:545-551.
Van-Essen-Zandvliett EE, Hughes MD, Waalkens HJ, Duiverman EJ, Kerrebijn KF. Remission of childhood asthma after long-term treatment with inhaled corticosteroid (budesonide): Can it be achieved? Dutch CNLSD Study Group. Eur Respir J 1994;7:63-68.
Brown PJ, Greville HW, Finucane KE. Asthma and irreversible airflow obstruction. Thorax 1984; 39:131-136.
Ferguson AC. Persisting airway obstruction in asymptomatic children with asthma with normal peak expiratory flow rates. J Allergy Clin Immunol 1988; 82:19-22.
Lazaar AL, Panettieri RA Jr. Is airway remodeling clinically relevant in asthma? Am J Med 2003;115: 652-659.
Barnes PJ, Liew FW. Why does asthma become persistent? Am J Respir Crit Care Med 1996;153 (Suppl):23-25.
Elias JA. Airway remodeling in asthma. Unanswered questions. Am J Respir Crit Care Med 2000;161(Suppl):168-171.
Rennard SI. Extracellular matrix. Am J Respir Crit Care Med 1996;153(Suppl):14-15.
Messer J, Peters G, Bennett W. Causes of deaths and pathological findings in 304 cases of bronchial asthma. Brit J Dis Chest 1960;38:616-624.
Saetta M, Di-Stefano A, Rosina C, Thiene G, Fabbri LM. Quantitative structural analysis of peripheral airways and arteries in sudden fatal asthma. Am Rev Respir Dis 1991;143:138-143.
Aikawa T, Shimura S, Sasaki H, Ebina M, Takishima T. Marked goblet cell hyperplasia with mucus accumulation in the airways of patients who died of severe acute asthma attack. Chest 1992;101:916-921.
Sakula A. Charcot-Leyden crystals and Curschmann spirals in asthmatic sputum. Thorax 1986;41:503-507.
Shak S, Capon DJ, Hellmiss R, Marsters SA, Baker CL. Recombinant human DNase I reduces the viscosity of cystic fibrosis sputum. Proc Natl Acad Sci USA 1990;7:9188-9192.
Kearney CE, Wallis CE. Deoxyribonuclease for cystic fibrosis. Cochrane Database Syst Rev 2000;2: CD00 1127.
Furuya MEY, Lezana-Fernández JL, Vargas MH, Hernández-Sierra JF, Ramírez-Figueroa JL. Efficacy of recombinant human DNase in pediatric patients with cystic fibrosis. Arch Med Res 2000;32:30-34.
Harms HK, Matouk E, Tournier G, et al. Multicenter, open-label study of recombinant human DNase in cystic fibrosis patients with moderate lung disease. DNase International Study Group. Pediatr Pulmonol 1998;26: 155-161.
Chernick WS, Barbero GJ. Composition of tracheobronchial secretions in cystic fibrosis of the pancreas and bronchiectasis. Pediatrics 1959;24:739-745.
Fahy JV, Steiger DJ, Liu J, Basbaum CB, Finkbeiner WE, Boushey HA. Markers of mucus secretion and DNA levels in induced sputum from asthmatic and from healthy subjects. Am Rev Respir Dis 1993;147: 1132-1137.
Gershan WM, Rusakow LS, Chetty A, Splaingard ML. Resolution of chronic atelectasis in a child with asthma after aerosolized recombinant human DNase. Pediatr Pulmonol 1994;18:266-269.
Greally P. Human recombinant DNase for mucus plugging in status asthmaticus. Lancet 1995;346: 1423-1424.
Puterman AS, Weinberg EG. RhDNase in acute asthma. Pediatr Pulmonol 1997;23:316-317.
Patel A, Harrison E, Durward A, Murdoch IA. Intratracheal recombinant human deoxyribonuclease in acute life-threatening asthma refractory to conventional treatment. Br J Anaesth 2000;84:505-507.
Durward A, Forte V, Shemie SD. Resolution of mucus plugging and atelectasis after intratracheal rhDNase therapy in mechanically ventilated child with refractory status asthmaticus. Crit Care Med 2000;28:560-562.
Zahm JM, Galabert C, Chaffin A, Chazalette JP, Grosskipf C, Puchelle E. Improvement of cystic fibrosis airway mucus transportability by recombinant human Dnase is related to changes in phospholipid profile. Am J Respir Crit Care Med 1998;157:1779-1784.
Slayter HS, Lamblin G, Le Truet A, et al. Complex structure of human bronchial mucus glycoprotein. Eur J Biochem 1984;142:209-218.
Bhaskar KR, O’Sullivan DD, Coles SJ, Kozakewich H, Vawter GP, Reid LM. Characterization of airway mucus from a fatal case of status asthmaticus. Pediatr Pulmonol 1988;5:176-182.
GINA. Global initiative for asthma. National Institutes of Health, Publication No. 95-3659, 1996.
Juniper EF, Guyatt GH, Epstein RS, Ferrie PJ, Jaeschke R, Hiller TK. Evaluation of impairment of health related quality of life in asthma: development of a questionnaire for use in clinical trials. Thorax 1992;47:76-83.
Sanjuas C, Alonso J, Sanchis J, et al. Cuestionario de calidad de vida en pacientes con asma: la versión española del Asthma Quality of Life Questionnaire. Arch Bronconeumol 1995;31:219-226.
American Thoracic Society. Standardization of spirometry. 1994 update. Am J Respir Crit Care Med 1995;152:1107-1136.
Quanjer P. Standardized lung function testing. Bull Eur Physiopathol Respir 1983;19(Suppl 5):1-95.
Zar JH. Biostatistical analysis. 4ª ed. Upper Saddle River: Prentice Hall; 1999. p. 336-337.
American Thoracic Society. Lung function testing: selection of reference values and interpretive strategies. Am Rev Respir Dis 1991;144:1202-1219.
Di Franco A, Bartoli ML, Carnevali S, et al. Analysis of sputum cell counts during spontaneous moderate exacerbations of asthma in comparison to the stable phase. J Asthma 2003;40:155-162.
Ordonez CL, Shaughnessy TE, Matthay MA, Fahy JV. Increased neutrophil numbers and IL-8 levels in airway secretions in acute severe asthma: Clinical and biologic significance. Am J Respir Crit Care Med 2000;161:1185-1190.
Tonnel AB, Gosset P, Tillie-Leblond I. Characteristics of the inflammatory response in bronchial lavage fluids from patients with status asthmaticus. Int Arch Allergy Immunol 2001;124:267-271.
Nguyen BP, Wilson SR, German DF. Patients’ perceptions compared with objective ratings of asthma severity. Ann Allergy Asthma Immunol 1996;77:209-215.
Weiner P, Berar-Yanay N, Davidovich A, Magadle R, Weiner M. The perception of dyspnea in patients with asthma, before and following treatment with inhaled glucocorticosteroids. Respir Med 2000;94:161-165.
Noseda A. Dyspnea and perception of airway obstruction. Rev Mal Respir 2003;20:364-372.