The Role of Nebulized Therapy in the Management of COPD: Evidence and Recommendations

References

• Global Initiative for Asthma (GINA), National Heart, Lung and Blood Institute, National Institutes of Health: GINA Report, Global Strategy for Asthma management and prevention, November 2006. Available at http://www.ginasthma.com. Accessed January 2011.
   Google Scholar
• National Asthma Education and Prevention Program, National Institutes of Health: Expert Panel Report 3: Guidelines for the diagnosis and management of asthma. Bethesda, MD, National Institutes of Health, 2007. Available at: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm. Accessed January 2011.
   Google Scholar
• GOLD. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease, Global initiative for chronic obstructive lung disease (GOLD). 2010 Available at: http://www.goldcopd.org/download.asp?intId = 608. Accessed February 2011.
   Google Scholar
• American Thoracic Society. Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease (COPD) and asthma. Am Rev Respir Dis 1987; 136:225–244.
   PubMed Web of Science ®Google Scholar
• Canadian Thoracic Society. Canadian Thoracic Society Guidelines for COPD. Available at http://www.copdguidelines.ca. Accessed April 2011.
   Google Scholar
• Dolovich MB, Dhand R. Aerosol drug delivery: Developments in design and clinical use. Lancet 2011; 377 (No 9770): 1032–1045.
   PubMed Web of Science ®Google Scholar
• Ram FS, Brocklebank DM, Muers M, Wright J, Jones PW. Pressurised metered-dose inhalers versus all other hand-held inhalers devices to deliver bronchodilators for chronic obstructive pulmonary disease Cochrane Database Systematic Rev 2002;(1):CD002170.
   Google Scholar
• Ram FS, Brocklebank DM, White J, Wright JP, Jones P. Pressurised metered dose inhalers versus all other hand-held inhaler devices to deliver beta2-agonist bronchodilators for non-acute asthma. Cochrane Database Systematic Rev 2002;(1):CD002158.
   Google Scholar
• Dolovich M, Ahrens R, Hess D, Device selection and outcomes of aerosol therapy: evidence-based guidelines. Chest 2005; 127:335–371.
   PubMed Web of Science ®Google Scholar
• Melani AS, Zanchetta D, Barbato N, Inhalation technique and variables associated with misuse of conventional metered-dose inhalers and newer dry powder inhalers in experienced adults. Ann Allergy Asthma Immunol 2004; 93:439–446.
   PubMed Web of Science ®Google Scholar
• Melani AS, Bonavia M, Cilenti V, Inhaler mishandling remains common in real life and is associated with reduced disease control. Respir Med 2011; doi:10.1016/j.rmed.2011.01.005.
   PubMed Web of Science ®Google Scholar
• Restrepo RD, Alvarez MT, Wittnebel LD, Sorenson H, Wettstein R. Medication adherence issues in patients treated for COPD. Int J COPD 2008; 3(3):371–384.
   Google Scholar
• Laube BL, Janssens HM, de Jongh FHC, What the pulmonary specialist should know about the new inhalation therapies. Eur Respir J 2011; 37:1308–1331.
   PubMed Web of Science ®Google Scholar
• Kesser KC, Geller DE. New aerosol delivery devices for cystic fibrosis. Respir Care. 2009 Jun; 54(6):754–767; discussion 767–768.
   PubMed Web of Science ®Google Scholar
• Dhand R. Inhalation therapy in invasive and noninvasive mechanical ventilation. Curr Opin Crit Care 2007; 13:27–38.
   PubMed Web of Science ®Google Scholar
• Yu AP, Guerin A, Ponce de Leon D, Therapy persistence and adherence in patients with chronic obstructive pulmonary disease: multiple versus single long-acting maintenance inhalers. J Med Econ 2011;14:486–496.
   PubMedGoogle Scholar
• van der Palen J, Klein JJ, van Herwaarden CL, Zielhuis GA, Seydel ER. Multiple inhalers confuse asthma patients. Eur Respir J 1999; 14:1034–1037.
   PubMed Web of Science ®Google Scholar
• Geller DE. Comparing clinical features of the nebulizer, metered-dose inhaler, and dry powder inhaler. Respir Care 2005; 50:1313–21.
   PubMedGoogle Scholar
• Newman SP. Inhaler treatment options in COPD. Eur Resp Rev 2005; 14:102–108.
   Google Scholar
• Wildhaber JH, Devadason SG, Eber E, Effect of electrostatic charge, flow, delay and multiple actuations on the in vitro delivery of salbutamol from different small volume spacers for infants. Thorax 1996; 51(10):985–988.
   PubMed Web of Science ®Google Scholar
• Lauricella S, Dolovich M. The effects of inhalation delay and spacer pretreatment on HFA-pMDI delivery from several small volume valved holding chambers. J Aerosol Med 2007; 20:202.
   Google Scholar
• McFadden ER. Improper patient techniques with metered dose inhalers: clinical consequences and solutions to misuse. J Allergy Clin Immunol 1995; 96:278–283.
   PubMed Web of Science ®Google Scholar
• Newman SP, Weisz AWB, Talaee N, Clarke SW. Improvement of drug delivery with a breath actuated pressurized aerosol for patients with poor inhaler technique. Thorax 2001; 46:712–16.
   Google Scholar
• Mitchell JP, Nagel MW. Valved Holding Chambers (VHCs) for use with pressurized metered dose inhalers (pMDIs): a review of causes of inconsistent medication delivery. Prim Care Resp J 2007; 16(4): 7–14.
   PubMedGoogle Scholar
• Rau JL. The inhalation of drugs: advantages and problems. Respir Care 2005; 50(3):367–382.
   PubMedGoogle Scholar
• Hodder R, Price D. Patient preferences for inhaler devices in chronic obstructive pulmonary disease: experience with Respimat® Soft Mist™Inhaler. Int J COPD 2009; 4:381–390.
   Google Scholar
• Quinet P, Young CA, Heritier F. The use of dry powder inhaler devices by elderly patients suffering from chronic obstructive pulmonary disease. Ann Physical Rehab Med 2010; 53(2): 69–76.
   PubMedGoogle Scholar
• Wieshammer S, Dreyhaupt J. Dry Powder Inhalers: Which Factors Determine the Frequency of Handling Errors? Respiration 2008; 75:18–25.
   PubMed Web of Science ®Google Scholar
• Corcoran TE, Dauber JH, Chigier N, Iacono AT. Improving drug delivery from medical nebulizers: the effects of increased nebulizer flow rates and reservoirs. J Aerosol Med 2002; 15;271–282.
   PubMedGoogle Scholar
• Rau JL, Ari A, Restrepo RD. Performance comparison of nebulizer designs: constant-output, breath-enhanced, and dosimetric. Respir Care 2004; 49:174–179.
   PubMedGoogle Scholar
• Dhand R, Giri VV, Noth I, Lissin D, Fishman RS, Taylor K. Bronchodilator response to ipratropium delivered via Aerodose inhaler or Pari LC Plus nebulizer in COPD. Am J Respir Crit Care Med 2002; 165:A593.
   Google Scholar
• Abdelrahim ME, Plant P, Chrystyn H. In-vitro characterization of the nebulized dose during non-invasive ventilation. J Pharmacy Pharmacol 2010; 62:966–972.
   PubMed Web of Science ®Google Scholar
• de Moraes Souza ML, Meneghini AC, Ferraz E, Vianna EO, Borges MC. Knowledge of and technique for using inhalation devices among asthma patients and COPD patients. J Bras Pneumol 2009; 35(9):824–831.
   PubMed Web of Science ®Google Scholar
• American Association of Respiratory Care Aerosol Delivery Guide. Available at http://www.aarc.org/education/aerosol_devices/ aerosol_delivery guide2.pdf. Accessed September 2011.
   Google Scholar
• American College of Chest Physicians Patient Guides: Patient Instructions for Inhaled Devices. Available at http://www.chestnet.org/accp/patient-guides/patient-instructions-inhaled-devices-english-and-spanish. Accessed September 2011.
   Google Scholar
• Anderson P. Use of Respimat® Soft Mist™Inhaler in COPD patients. Int J COPD. 2006; 1(3):251–259.
   Google Scholar
• GfK Market Measures. COPD ATU, Q4 2008;Q 1g.
   Google Scholar
• COPD e-Newsletter. Available at http://www.nhlbi.nih.gov/health/public/lung/copd./ Accessed April 2011.
   Google Scholar
• Celli BR, Thomas NE, Anderson JA, Effect of pharmacotherapy on rate of decline of lung function in chronic obstructive pulmonary disease: results from the TORCH study. Am J Respir Crit Care Med 2008; 178:332–338.
   PubMed Web of Science ®Google Scholar
• British Thoracic Society. Guidelines for the management of chronic obstructive pulmonary disease. Thorax 1997; 52:S1–S28.
   PubMedGoogle Scholar
• ATS/ERS Task Force. Standards for the diagnosis and management of patients with COPD. American Thoracic Society and European Respiratory Society 2004. Available at: www.thoracic.org/clinical/copd-guidelines/resources/copddoc.pdf. Accessed February 2011.
   Google Scholar
• Colice GL. Nebulized bronchodilators for outpatient management of stable chronic obstructive pulmonary disease. Am J Med 1996; 100 (Suppl 1A): 11–18.
   Google Scholar
• Friedman M. A multicenter study of nebulized bronchodilator solutions in chronic obstructive pulmonary disease. Am J Med. 1996; 100 (Suppl 1A): 30–39.
   Google Scholar
• Brophy C, Kastelik JA, Gardiner E, Greenstone MA. Quality of life measurements and bronchodilator responsiveness in prescribing nebulizer therapy in COPD. Chronic Respir Dis 2008; 5:13–18.
   PubMedGoogle Scholar
• The COMBIVENT Inhalation Solution Study Group. Routine nebulized ipratropium and albuterol together are better than either alone in COPD. Chest 1997; 112:1514–1521.
   PubMed Web of Science ®Google Scholar
• Gross N, Tashkin D, Miller R, Oren J, Coleman W, Linberg S. Inhalation by nebulization of albuterol-ipratropium combination (Dey combination) is superior to either agent alone in the treatment of chronic obstructive pulmonary disease. Dey Combination Solution Study Group. Respiration 1998; 65:354–362.
   PubMed Web of Science ®Google Scholar
• Levin DC, Little KS, Laughline KR, Addition of anticholinergic solution prolongs bronchodilator effect of ß2 agonists in patients with chronic obstructive pulmonary disease. Am J Med 1996; 100 (Suppl 1A): 40–48.
   Google Scholar
• Tashkin DP, Bleecker E, Braun S, Results of a multicenter study of nebulized inhalant bronchodilator solutions. Am J Med 1996; 100 (Suppl 1A):62–69.
   Google Scholar
• Tashkin DP, Klein GL, Colman SS, Zayed H, Schonfeld WH. Comparing COPD treatment: Nebulized, metered dose, inhaler, and concomitant therapy. Am J Med 2007; 120:435–441.
   PubMed Web of Science ®Google Scholar
• Baumgartner RA, Hanania NA, Calhoun WJ, Nebulized arformoterol in patients with COPD: a 12-week, multicenter, randomized, double-blind, double-dummy, placebo- and active-controlled trial. Clin Therap 2007; 29:261–278.
   PubMed Web of Science ®Google Scholar
• Donohue JF, Hanania NA, Fogarty C, Long-term safety of nebulized formoterol: Results of a twelve-month open label clinical trial. Ther Adv Respir Dis 2008a; 2:199–208.
   PubMedGoogle Scholar
• Donohue JF, Hanania NA, Sciarappa KA, Arformoterol and salmeterol in the treatment of chronic obstructive pulmonary disease: A one year evaluation of safety and tolerance. Therap Adv Respir Dis 2008b: 2:37–48.
   PubMedGoogle Scholar
• Gross N, Nelson HS, Lapidus RJ, Efficacy and safety of formoterol fumarate delivered by nebulization to COPD patients. Respir Med 2008; 102:189–197.
   PubMed Web of Science ®Google Scholar
• Hanania NA, Boota A, Kerwin E, Tomlinson L, Denis-Mize K. Efficacy and safety of nebulized formoterol as add-on therapy in COPD patients receiving maintenance tiotropium bromide: Results from a 6-week, randomized, placebo-controlled, clinical trial. Drugs 2009; 69:1205–1216.
   PubMed Web of Science ®Google Scholar
• Hanania NA, Donohue JF, Nelson H, The safety and efficacy of arformoterol and formoterol in COPD. COPD 2010; 7:17–31.
   PubMedGoogle Scholar
• Hanrahan JP, Hanania NA, Calhoun WJ, Effect of nebulized arformoterol on airway function in COPD: results from two randomized trials. COPD 2008; 5:25–34.
   PubMedGoogle Scholar
• Sutherland ER, Brazinsky S, Feldman G, Nebulized formoterol effect on bronchodilation and satsfaction in COPD patients compared to QID ipratropium/albuterol MDI. Curr Med Res Opin 2009; 25:653–661.
   PubMed Web of Science ®Google Scholar
• Tashkin DP, Littner M, Andrews CP, Concomitant treatment with nebulized formoterol and tiotropium in subjects with COPD: a placebo-controlled trial. Respir Med 2008; 102:479–487.
   PubMed Web of Science ®Google Scholar
• Paggiaro PL, Vagaggini B, DiFranco A, Efficacy of nebulized flunisolide combined with salbutamol and ipratropium bromide in stable patients with moderate-to-severe chronic obstructive pulmonary disease. Respiration 2006; 73:603–609.
   PubMed Web of Science ®Google Scholar
• BROVANA® (arformoterol tartrate) Inhalation Solution 15 mcg/2mL. Prescribing Information. Sunovion Pharmaceuticals, Inc., Marlborough, MA.
   Google Scholar
• Perforomist® (formoterol fumarate) Inhalation Solution 20 mcg/2mL Prescribing Information. Dey Pharma LP, Basking Ridge, NJ.
   Google Scholar
• Pulmicort Respules® (budesonide inhalation suspension). Prescribing Information. AstraZeneca LP, Wilmington DE.
   Google Scholar
• Hurst JR, Vestbo J, Anzueto A, Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Investigators. Susceptibility to exacerbation in chronic obstructive pulmonary disease. N Engl J Med 2010; 363:1128–1138.
   PubMed Web of Science ®Google Scholar
• Calverley PM, Rennard S, Nelson HS, One-year treatment with mometasone furoate in chronic obstructive pulmonary disease. Respir Res 2008; 9(1):73.
   PubMedGoogle Scholar
• Goodman DE, Israel E, Rosenberg M, The influence of age, diagnosis, and gender on proper use of metered-dose inhalers. Am J Respir Crit Care Med 1994; 150:1256–1261.
   PubMed Web of Science ®Google Scholar
• Barta SK, Crawford A, Roberts CM. Survey of patients’ views of domiciliary nebulizer treatment for chronic lung disease. Respir Med 2002; 96:375–381.
   PubMed Web of Science ®Google Scholar
• Marcus P. The role of nebulized inhaled corticosteroid therapy in adult patients with asthma and chronic obstructive pulmonary disease. Adv Ther 2005; 22(4):407–418.
   PubMed Web of Science ®Google Scholar
• Dhand R. Nebulizers that use a vibrating mesh or plate with multiple apertures to generate aerosol. Respir Care 2002; 47:1406–1416.
   PubMedGoogle Scholar
• Stoller JK. Clinical practice: acute exacerbations of chronic obstructive pulmonary disease. N Engl J Med 2002; 346:988–994.
   PubMed Web of Science ®Google Scholar
• McCrory DC, Brown LE. Anticholinergic bronchodilators versus beta2-sympathomimetic agents for acute exacerbations of chronic obstructive pulmonary disease (review). The Cochrane Library 2003 (issue 1): 1–24.
   Google Scholar
• Snow V, Lascher S, Mottur-Pilson C, Joint Expert Panel on Chronic Obstructive Pulmonary Disease of the American College of Chest Physicians and the American College of Physicians-American Society of Internal Medicine. Evidence base for management of acute exacerbations of chronic obstructive pulmonary disease. Ann Intern Med 2001; 134:595–599.
   PubMed Web of Science ®Google Scholar
• Bach PB, Brown C, Gelfand SE, McCrory DC. Management of acute exacerbations of chronic obstructive pulmonary disease: a summary and appraisal of published evidence. Ann Intern Med 2001; 134:600–620.
   PubMed Web of Science ®Google Scholar
• Cydulka RK, Emerman CL. Effects of combined treatment with glycopyrrolate and albuterol in acute exacerbation of chronic obstructive pulmonary disease. Ann Emerg Med 1995; 25:470–473.
   PubMed Web of Science ®Google Scholar
• O’Driscoll, BR, Taylor, RJ, Horsley, MG, Chambers DK, Bernstein A. Nebulised salbutamol with and without ipratropium bromide in acute airflow obstruction. Lancet 1989; 1:1418–1420.
   PubMed Web of Science ®Google Scholar
• Karpel, JP. Bronchodilator responses to anticholinergic and beta-adrenergic agents in acute and stable COPD. Chest 1991; 99:871–876.
   PubMed Web of Science ®Google Scholar
• Khoukaz G, Gross NJ. Effects of salmeterol on arterial blood gases in patients with stable chronic obstructive pulmonary disease: comparison with albuterol and ipratropium. Am J Respir Crit Care Med 1999; 160:1028–1030.
   PubMed Web of Science ®Google Scholar
• Polverino E, Gomez FP, Manrique H, Gas exchange response to short-acting_2-agonists in chronic obstructive pulmonary disease severe exacerbations. Am J Respir Crit Care Med 2007; 176:350–355.
   PubMed Web of Science ®Google Scholar
• Suissa S, Assimes T, Ernst P. Inhaled short acting beta agonist use in COPD and the risk of acute myocardial infarction. Thorax 2003; 58:43–46.
   PubMed Web of Science ®Google Scholar
• Stockley RA, Chopra N, Rice L. Addition of salmeterol to existing treatment in patients with COPD: a 12 month study. Thorax 2006; 61:122–28.
   PubMed Web of Science ®Google Scholar
• Stockley RA, Whitehead PJ, Williams MK. Improved outcomes in patients with chronic obstructive pulmonary disease treated with salmeterol compared with placebo/usual therapy: results of a meta-analysis. Respir Res 2006b; 7:147.
   PubMed Web of Science ®Google Scholar
• Sin DD, McAlister FA, Man SF, Anthonisen NR. Contemporary management of chronic obstructive pulmonary disease: scientific review. JAMA 2003; 290:2301–2312.
   PubMed Web of Science ®Google Scholar
• Niewoehner DE, Rice K, Cote C, Prevention of exacerbations of chronic obstructive pulmonary disease with tiotropium, a once-daily inhaled anticholinergic bronchodilator: a randomized trial. Ann Intern Med 2005; 143:317–326.
   PubMed Web of Science ®Google Scholar
• Mahler DA, Donohue JF, Barbee RA, Efficacy of salmeterol xinafoate in the treatment of COPD. Chest 1999; 115:957–965.
   PubMed Web of Science ®Google Scholar
• Cazzola M, Santus P, Matera MG, A single high dose of formoterol is as effective as the same dose administered in a cumulative manner in patients with acute exacerbation of COPD. Respir Med 2003; 97:458–462.
   PubMed Web of Science ®Google Scholar
• Di MF, Verga M, Santus P, Effect of formoterol, tiotropium, and their combination in patients with acute exacerbation of chronic obstructive pulmonary disease: a pilot study. Respir Med 2006; 100:1925–1932.
   PubMed Web of Science ®Google Scholar
• Colice GL, Carnathan B, Sung J, Paramore LC. A respiratory therapist-directed protocol for managing inpatients with asthma and COPD incorporating a long-acting bronchodilator. J Asthma 2005; 42:29–34.
   PubMed Web of Science ®Google Scholar
• Drescher GS, Carnathan BJ, Imus S, Colice GL. Incorporating tiotropium into a respiratory therapist-directed bronchodilator protocol for managing in-patients with COPD exacerbations decreases bronchodilator costs. Respir Care 2008; 53:1678–1684.
   PubMed Web of Science ®Google Scholar
• Quon, BS, Gan, WQ, Sin, DD. Contemporary management of acute exacerbations of COPD: a systematic review and metaanalysis. Chest 2008; 133:756–766.
   PubMed Web of Science ®Google Scholar
• Niewoehner DE, Erbland ML, Deupree RH, Effect of systemic glucocorticoids on exacerbations of chronic obstructive pulmonary disease. N Engl J Med 1999; 340:1941–1947.
   PubMed Web of Science ®Google Scholar
• Davies L, Angus RM, Calverley PM. Oral corticosteroids in patients admitted to hospital with exacerbations of chronic obstructive pulmonary disease: a prospective randomised controlled trial. Lancet 1999; 354:456–460.
   PubMed Web of Science ®Google Scholar
• Lindenauer, PK, Pekow, PS, Lahti MC, Association of corticosteroid dose and route of administration with risk of treatment failure in acute exacerbation of chronic obstructive pulmonary disease. JAMA 2010; 303:2359–2367.
   PubMed Web of Science ®Google Scholar
• de Jong YP, Uil SM, Grotjohan HP, Oral or IV prednisolone in the treatment of COPD exacerbations: a randomized, controlled, double-blind study. Chest 2007; 132:1741–1747.
   PubMed Web of Science ®Google Scholar
• Donaldson GC, Seemungal TAR, Bhowmik A, Wedzicha JA. Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease. Thorax 2002; 57:847–852.
   PubMed Web of Science ®Google Scholar
• Wilkinson TMA, Donaldson GC, Hurst JR, Seemungal TA, Wedzicha JA. Early therapy improves outcomes of exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2004; 169: 1298–1303.
   PubMed Web of Science ®Google Scholar
• Johansson SA, Andersson KE, Brattsand R, Gruvstad E, Hedner P. Topical and systemic glucocorticoid potencies of budesonide, beclomethasone dipropionate and prednisolone in man. Eur J Respir Dis Suppl 1982; 122:74–82.
   PubMedGoogle Scholar
• Brogden RN, McTavish D. Budesonide: an updated review of its pharmacological properties and therapeutic efficacy in asthma and rhinitis. Drugs 1992; 44:375–407.
   PubMed Web of Science ®Google Scholar
• Walsh LJ, Wong CA, Oborne J, Adverse effects of oral corticosteroids in relation to dose in patients with lung disease. Thorax 2001; 56:279–284.
   PubMed Web of Science ®Google Scholar
• Jones A, Fay JK, Burr M, Inhaled corticosteroid effect on bone metabolism in asthma and mild chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2002; CD003537.
   Google Scholar
• Richy F, Bousquet J, Ehrlich GE, Inhaled corticosteroids effects on bone in asthmatic and COPD patients: a quantitative systematic review. Osteoporos Int 2003; 14:179–190.
   PubMed Web of Science ®Google Scholar
• Belda J, Margarit G, Martinez C, Anti-inflammatory effects of high-dose inhaled fluticasone versus oral prednisone in asthma exacerbations. Eur Respir J 2007; 30:1143–1149.
   PubMed Web of Science ®Google Scholar
• Rodrigo GJ. Comparison of inhaled fluticasone with intravenous hydrocortisone in the treatment of adult acute asthma. Am J Respir Crit Care Med 2005; 171:1231–1236.
   PubMed Web of Science ®Google Scholar
• Levy ML, Stevenson C, Maslen T. Comparison of short courses of oral prednisolone and fluticasone propionate in the treatment of adults with acute exacerbations of asthma in primary care. Thorax 1996; 51:1087–1092.
   PubMed Web of Science ®Google Scholar
• Morice AH, Morris D, Lawson-Matthew B. A comparison of nebulized budesonide with oral prednisolone in the treatment of exacerbations of obstructive pulmonary disease. Clin Pharmacol Ther 1996; 60:675–678.
   PubMed Web of Science ®Google Scholar
• Maltais F, Ostinelli J, Bourbeau J, Comparison of nebulized budesonide and oral prednisolone with placebo in the treatment of acute exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2002; 165:698–703.
   PubMed Web of Science ®Google Scholar
• Mirici A, Akgun M. Comparison of the efficacy of nebulized budesonide with parenteral corticosteroids in the treatment of acute exacerbations of chronic obstructive pulmonary disease. Clin Drug Invest 2003; 23:55–62.
   PubMed Web of Science ®Google Scholar
• Gunen H, Hacievliyagil SS, Yetkin O, Gulbas G. The role of nebulized budesonide in the treatment of exacerbations of COPD. Eur Respir J 2007; 29:660–667.
   PubMed Web of Science ®Google Scholar
• Rodrigo G, Rodrigo C. Inhaled flunisolide for acute severe asthma. Am J Respir Crit Care Med 2000; 157:698–703.
   Web of Science ®Google Scholar
• McKenzie JE, Cruz-Rivera M. Compatibility of budesonide inhalation suspension with four nebulizing solutions. Ann Pharmacother 2004; 38:967–972.
   PubMed Web of Science ®Google Scholar