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• W2084236663 abstract "See related articles, p. 22 and p. 28.Be not the first by whom the new are tried nor yet the last to lay the old aside.—William PopeIn medical practice, despite the increasing acceptance of “evidence-based” therapeutics, the “tried and true” may persist long after the evidence is overwhelmingly in favor of change. The articles by Schuh et al1Schuh S Johnson DW Stephens D Callahan S Winders P Canny GJ. Comparison of albuterol delivered by a metered dose inhaler with spacer versus a nebulizer in children with mild acute asthma.J Pediatr. 1999; 135: 22-27Abstract Full Text Full Text PDF PubMed Scopus (100) Google Scholar in Toronto and by Wildhaber et al2Wildhaber JH Dore ND Wilson JM Devadason SG LeSoëf PN. Inhalation therapy in asthma: Nebulizer or pressurized metered-dose inhaler with holding chamber? In vivo comparison of lung deposition in children.J Pediatr. 1999; 135: 28-33Abstract Full Text Full Text PDF PubMed Scopus (140) Google Scholar in Perth in this issue of The Journal contribute interesting new data and commentary to a debate that has continued unabated for at least 2 decades—the notion that aerosol therapy with bronchodilators for severe exacerbations of asthma or chronic obstructive pulmonary disease should be administered by small-volume nebulizers and that metered-dose inhalers should be reserved for mild to moderate asthma attacks or for maintenance therapy.Development of valved aerosol holding chambers as MDI accessory devices to make MDIs more patient friendly and versatile began about 20 years ago, shortly after spacers were introduced as a means of extending the MDI mouthpiece to reduce aerosol impaction in the mouth and throat. By applying an improved understanding of aerosol physics3Corr D Dolovich M McCormack D Ruffin R Obminski G Newhouse M. Design and characteristics of a portable breath actuated, particle size selective medical aerosol inhaler.J Aerosol Sci. 1982; 13: 1-7Crossref Scopus (72) Google Scholar and receptor sites in the airways,4Barnes PJ. Muscarinic receptors in airways: recent developments.J Appl Physiol. 1990; 68: 1777Crossref PubMed Scopus (7) Google Scholar, 5Barnes PJ Basbaum CB Nadel JA. Autoradiograph localization of autonomic receptors in airway smooth muscle: marked difference between large and small airways.Am Rev Respir Dis. 1983; 127: 758-762PubMed Google Scholar VHCs introduced a new “low tech” paradigm to the therapy of reversible airflow obstruction. These relatively small MDI add-on devices improved pulmonary drug targeting and the efficiency and versatility of MDIs,6Newhouse MT Dolovich MB. Control of asthma by aerosols.N Engl J Med. 1986; 315: 870-874Crossref PubMed Scopus (206) Google Scholar and by taking a “systems” approach with patient- and task-specific accessories, they became capable of supplanting SVNs in clinical settings ranging from bronchopulmonary dysplasia in neonates7Fok TF Monkman S Dolovich M Gray S Coates G Paes B et al.Efficiency of aerosol medical delivery from a metered dose inhaler versus jet nebulizer in infants with bronchopulmonary dysplasia.Pediatr Pulmonol. 1996; 21: 301-309Crossref PubMed Scopus (172) Google Scholar to heaves (asthma) in horses!8Tesarowski DB Viel L McDonnell WN Newhouse MT. The rapid and effective administration of a β2 -agonist to horses with heaves using a compact inhalation device and metered-dose inhalers.Can Vet J. 1994; 35: 170-173PubMed Google ScholarVHCs were initially intended to overcome the fairly common problem of poor hand-breath coordination in adults, and their versatility was gradually augmented by the introduction of masks of various sizes to replace the mouthpiece for treating tidal-breathing infants and children,9Gervais A Begin P. Bronchodilatation with a MDI plus an extension using tidal breathing versus jet nebulization.Chest. 1987; 92: 822-824Crossref PubMed Scopus (17) Google Scholar, 10Ba M Spier S Lapierre G Lamarre A. Wet nebulizer versus spacer and metered dose inhaler via tidal breathing.J Asthma. 1989; 26: 355-358Crossref PubMed Scopus (19) Google Scholar as well as frail older adults and intellectually challenged patients.11Nair LG Diamond R Falcone G Thakore S Fine JM. Fine efficacy of mask spacer with metered dose inhaler in the frail elderly.Chest. 1995; 108: 216sCrossref PubMed Scopus (65) Google Scholar Patients requiring intubation and assisted ventilation could also be treated more efficiently and cost-effectively with MDIs for providing β-agonist and anticholinergic aerosol therapy, as ventilator-compatible accessory devices were developed.12Dhand R Tobin MJ. Inhaled bronchodilator therapy in mechanically ventilated asthma.Am J Respir Crit Care Med. 1997; 156: 3-10Crossref PubMed Scopus (167) Google ScholarAs well-designed bronchodilator studies comparing MDI + VHC and SVN in severe acute asthma accumulated, it became evident that the addition of VHCs to MDIs allows the replacement of SVNs even in the most challenging clinical situations,13Newhouse MT. Emergency department management of life-threatening asthma: Are nebulizers obsolete?.Chest. 1993; 103: 661-662Crossref PubMed Scopus (32) Google Scholar with the obvious exception of those in which no MDI formulation is available (eg, dornase alfa, inhaled antibiotics).For administration of aerosol bronchodilators to patients with severe, life-threatening asthma in the emergency department, a recent meta-analysis14Turner MO Patel A Ginsburg S Fitzgerald JM. Bronchodilator delivery in acute airflow obstruction. A meta-analysis.Arch Intern Med. 1997; 157: 1736-1744Crossref PubMed Google Scholar confirmed that MDI + VHC was therapeutically equivalent to SVNs overall but with more rapid rescue,14Turner MO Patel A Ginsburg S Fitzgerald JM. Bronchodilator delivery in acute airflow obstruction. A meta-analysis.Arch Intern Med. 1997; 157: 1736-1744Crossref PubMed Google Scholar, 15Hodder RV Calcutt LE Leach JA. Metered dose inhaler with spacer is superior to wet nebulisation for emergency room treatment of acute, severe asthma [abstract].Chest. 1988; 94: 52SGoogle Scholar fewer side effects,16Lee N Rachelefsky G Kobayashi RH Kobayashi AL Siegel SC Katz RM et al.Comparison of efficacy and safety of albuterol administered by power-driven nebulizer (PND) versus metered dose inhaler (MDI) with Aerochamber and mask in young children with acute asthma [abstract].J Allergy Clin Immunol. 1991; 87: 307Abstract Full Text PDF Google Scholar lower cost per treatment,17Turner MO Gafni A Swan D Fitzgerald JM. A review and economic evaluation of bronchodilator delivery methods in hospitalized patients.Arch Intern Med. 1996; 156: 2113-2118Crossref PubMed Google Scholar and a lower mortality rate in adults with coronary artery disease.18Suissa S Hemmelgarn B Blais L Ernst P. Bronchodilators and acute cardiac death.Am J Respir Crit Care Med. 1996; 154: 1598-1602Crossref PubMed Scopus (125) Google Scholar VHCs provide these benefits by their ability to decrease the oropharyngeal deposition of bronchodilators (or corticosteroids) by 80% to 90% and the total body dose by about 75%, thus improving the therapeutic ratio and drug targeting to the lower respiratory tract.19Dolovich M Ruffin R Corr D Newhouse MT. Clinical evaluation of a simple demand inhalation MDI aerosol delivery device.Chest. 1983; 84: 36-41Crossref PubMed Scopus (130) Google Scholar This is accomplished with lower device and drug costs, while providing much greater portability, freedom from carrying liquid solutions, independence from a power source, and no risk of disseminating infection from contaminated ventilator circuits or poorly serviced SVNs.20Craven DE Lichtenberg DA Goularte TA Make BJ McCabe WR. Contaminated medication nebulizers in mechanical ventilator circuits, Source of bacterial aerosols.Am J Med. 1984; 77: 834-838Abstract Full Text PDF PubMed Scopus (137) Google Scholar, 21Barnes KL Clifford R Holgate ST. Bacterial contamination of home nebulizers.Br Med J (Clin Res Ed). 1987; 295: 812Crossref PubMed Scopus (50) Google ScholarBased on the evidence, it appears that the debate has been resolved in favor of MDI + VHC, although many physicians and especially pediatricians, continue to prescribe SVNs for their patients, not only in hospital practice but for home use as well. Not surprisingly, many patients and caregivers therefore conclude that SVNs are, on balance, the optimum means of providing aerosol therapy for management of acute asthma, especially in children. Nothing could be further from the truth! The articles by Schuh et al1Schuh S Johnson DW Stephens D Callahan S Winders P Canny GJ. Comparison of albuterol delivered by a metered dose inhaler with spacer versus a nebulizer in children with mild acute asthma.J Pediatr. 1999; 135: 22-27Abstract Full Text Full Text PDF PubMed Scopus (100) Google Scholar and Wildhaber et al2Wildhaber JH Dore ND Wilson JM Devadason SG LeSoëf PN. Inhalation therapy in asthma: Nebulizer or pressurized metered-dose inhaler with holding chamber? In vivo comparison of lung deposition in children.J Pediatr. 1999; 135: 28-33Abstract Full Text Full Text PDF PubMed Scopus (140) Google Scholar take opposing sides of the controversy, with the latter presenting arguments, based on total dose and dose administered per minute, in favor of therapy with SVNs.The study by Schuh et al, like most other ED studies, supports the use of MDI + VHC as therapeutically equivalent to SVN in the treatment of asthma. Their double-blind, triple-dummy study further demonstrates that 200 μg of albuterol is therapeutically equivalent to a 0.15 mg/kg body weight adjusted dose of 600 to 1000 μg, an unnecessarily large dose of β-agonist whether delivered by Intec Whisperjet SVN or by AeroChamber MDI + VHC in these mild to moderate acute episodes. Adverse events, even in the high-dose group, were rare and relatively minor. The heart rate was significantly higher in the nebulizer group, possibly because of increased oropharyngeal and/or alveolar deposition, and therefore systemic albuterol absorption, with the SVN in contrast to the VHC.3Corr D Dolovich M McCormack D Ruffin R Obminski G Newhouse M. Design and characteristics of a portable breath actuated, particle size selective medical aerosol inhaler.J Aerosol Sci. 1982; 13: 1-7Crossref Scopus (72) Google Scholar, 19Dolovich M Ruffin R Corr D Newhouse MT. Clinical evaluation of a simple demand inhalation MDI aerosol delivery device.Chest. 1983; 84: 36-41Crossref PubMed Scopus (130) Google Scholar Although there was no significant difference in forced expiratory volume in 1 second between the treatment groups, there was a trend to a greater number of “excellent” responders in the high-dose MDI + VHC group and a greater number of “poor” responders in the SVN group. Perhaps most important with regard to the issue of patient preference and compliance (adherence) was the fact that 90% of the families opted for MDI + VHC for home use.Wildhaber et al2Wildhaber JH Dore ND Wilson JM Devadason SG LeSoëf PN. Inhalation therapy in asthma: Nebulizer or pressurized metered-dose inhaler with holding chamber? In vivo comparison of lung deposition in children.J Pediatr. 1999; 135: 28-33Abstract Full Text Full Text PDF PubMed Scopus (140) Google Scholar—in concluding that the SVN (Pari Boy38/Proneb Turbo and LC Star), which nebulized 2000 μg of salbutamol, was superior to 360 μg by MDI + VHC because it delivered a greater total dose and dose per minute to children’s lungs—create a “straw man.” In the very unlikely event that such a large dose (equivalent to more than 20 puffs of salbutamol by MDI) were clinically indicated, the MDI + VHC could readily provide it with dose titration at the rate of 1 puff every 30 to 60 seconds and could do so more safely and economically.For a therapeutically equivalent dose, not likely to exceed 4 to 6 puffs even in severe acute asthma, 2 to 4 minutes would suffice; and the medication could be administered by the admitting physician or nurse while the history and physical examination are performed. Furthermore, the calculation of Wildhaber et al2Wildhaber JH Dore ND Wilson JM Devadason SG LeSoëf PN. Inhalation therapy in asthma: Nebulizer or pressurized metered-dose inhaler with holding chamber? In vivo comparison of lung deposition in children.J Pediatr. 1999; 135: 28-33Abstract Full Text Full Text PDF PubMed Scopus (140) Google Scholar does not take into account the time required to assemble, disassemble, and clean the SVN, which must be done on each occasion; whereas the MDI nozzle and VHC do not require cleaning more than once a week.Furthermore, there is additional benefit to using the same device in the ED as the patient uses at home for maintenance therapy. It provides an opportunity to review good inhalation technique at a time when the patient or caregiver is particularly motivated, while at the same time delivering a clear message that the MDI + VHC that the child has been prescribed for home use is effective enough for the treatment of even the sickest patients in the hospital.14Turner MO Patel A Ginsburg S Fitzgerald JM. Bronchodilator delivery in acute airflow obstruction. A meta-analysis.Arch Intern Med. 1997; 157: 1736-1744Crossref PubMed Google Scholar, 17Turner MO Gafni A Swan D Fitzgerald JM. A review and economic evaluation of bronchodilator delivery methods in hospitalized patients.Arch Intern Med. 1996; 156: 2113-2118Crossref PubMed Google Scholar, 22Amirav I Newhouse MT. Metered-dose inhaler accessory devices in acute asthma. Efficacy and comparison with nebulizers: a literature review.Arch Pediatr Adolesc Med. 1997; 151: 876-882Crossref PubMed Scopus (83) Google ScholarBut are the data of Schuh et al1Schuh S Johnson DW Stephens D Callahan S Winders P Canny GJ. Comparison of albuterol delivered by a metered dose inhaler with spacer versus a nebulizer in children with mild acute asthma.J Pediatr. 1999; 135: 22-27Abstract Full Text Full Text PDF PubMed Scopus (100) Google Scholar generalizable to patients with more severe acute asthma? Two recent literature reviews suggest that they are. In a critical review of acute ED asthma therapy in children, Amirav and Newhouse concluded that MDI + VHC was as effective as SVN for relieving bronchospasm but at a dose, on average, about 6-fold smaller.22Amirav I Newhouse MT. Metered-dose inhaler accessory devices in acute asthma. Efficacy and comparison with nebulizers: a literature review.Arch Pediatr Adolesc Med. 1997; 151: 876-882Crossref PubMed Scopus (83) Google Scholar Turner et al14Turner MO Patel A Ginsburg S Fitzgerald JM. Bronchodilator delivery in acute airflow obstruction. A meta-analysis.Arch Intern Med. 1997; 157: 1736-1744Crossref PubMed Google Scholar arrived at a similar conclusion from their meta-analysis comparing β-agonist therapy delivered by MDI + VHC with that delivered by SVN in adults with severe acute asthma. These authors, in a separate study, also demonstrated the cost-benefit of MDI versus SVN therapy in the ED, confirming results of several previous studies.17Turner MO Gafni A Swan D Fitzgerald JM. A review and economic evaluation of bronchodilator delivery methods in hospitalized patients.Arch Intern Med. 1996; 156: 2113-2118Crossref PubMed Google ScholarWith an efficient VHC and fine particle fraction generated by the MDI, the doses needed to reach the plateau of the dose-response curve have generally been much smaller than those usually administered by SVN, which have ranged from 625 to 5000 μg in 2 to 3 mL of normal saline solution. Such large doses probably became commonplace because, in the past, most continuously operating nebulizers were notoriously inefficient (drug delivery efficiency <10%). With the development of more efficient and breath-activated SVNs, this could create a serious safety issue unless the “usual” dose is appropriately reduced. Indeed, it would be surprising if the SVN-delivered doses in the study by Wildhaber et al2Wildhaber JH Dore ND Wilson JM Devadason SG LeSoëf PN. Inhalation therapy in asthma: Nebulizer or pressurized metered-dose inhaler with holding chamber? In vivo comparison of lung deposition in children.J Pediatr. 1999; 135: 28-33Abstract Full Text Full Text PDF PubMed Scopus (140) Google Scholar did not cause tremor and tachycardia in many of their subjects.Standards for SVNs such as lower respiratory tract delivery efficiency are only now being developed by committees of the American and European thoracic societies and are not usually available from the manufacturers. There is considerable variability between (and sometimes even within) SVN models. Physicians should become very familiar with one or two efficient devices for which there is clinical trial support and try to avoid frequent switching based on a smooth sales presentation (frequently with a minimum of clinical data) or price alone. It should be emphasized that the same is true of VHCs, which may vary tremendously in quality, durability, fine-particle aerosol output, mask fit and dead space, inspiratory and expiratory valve resistance, and stiffness from one manufacturer to another.This is particularly true in pediatric practice in which, for example, mask dead space may be as low as 15 mL with inspiratory valve resistance of 0.6 cm H2 O/L/s at 20 L/min in the Aero- Chamber device used by Schuh et al1Schuh S Johnson DW Stephens D Callahan S Winders P Canny GJ. Comparison of albuterol delivered by a metered dose inhaler with spacer versus a nebulizer in children with mild acute asthma.J Pediatr. 1999; 135: 22-27Abstract Full Text Full Text PDF PubMed Scopus (100) Google Scholar and by Wildhaber et al2Wildhaber JH Dore ND Wilson JM Devadason SG LeSoëf PN. Inhalation therapy in asthma: Nebulizer or pressurized metered-dose inhaler with holding chamber? In vivo comparison of lung deposition in children.J Pediatr. 1999; 135: 28-33Abstract Full Text Full Text PDF PubMed Scopus (140) Google Scholar or as high as 50 mL (equivalent to a tidal volume at age 6 months) with valve resistance 2 to 5 times higher with other add-on devices.The radiolabeled salbutamol aerosol deposition study carried out by Wildhaber et al2Wildhaber JH Dore ND Wilson JM Devadason SG LeSoëf PN. Inhalation therapy in asthma: Nebulizer or pressurized metered-dose inhaler with holding chamber? In vivo comparison of lung deposition in children.J Pediatr. 1999; 135: 28-33Abstract Full Text Full Text PDF PubMed Scopus (140) Google Scholar with a static-free AeroChamber VHC brings important laboratory research to the bedside. Their in vitro studies demonstrated the adverse effect of electrostatic charge on the walls of plastic holding chamber devices on drug delivery efficiency and the benefit of simply coating the inside of the VHC with dishwashing detergent. They showed that they could deliver more than twice as much salbutamol aerosol to the lower respiratory tract2Wildhaber JH Dore ND Wilson JM Devadason SG LeSoëf PN. Inhalation therapy in asthma: Nebulizer or pressurized metered-dose inhaler with holding chamber? In vivo comparison of lung deposition in children.J Pediatr. 1999; 135: 28-33Abstract Full Text Full Text PDF PubMed Scopus (140) Google Scholar compared with previous studies in infants and young children.23Tal A Golan H Grauer N Aviram M Albin D Quastel MR. Deposition pattern of radiolabeled salbutamol inhaled from a metered-dose inhaler by means of a spacer with mask in young children with airway obstruction.J Pediatr. 1996; 128: 479-484Abstract Full Text Full Text PDF PubMed Scopus (204) Google ScholarAlso of interest is the issue of patient and caregiver preference with regard to the selection of an aerosol delivery system, which was raised by Wildhaber et al,2Wildhaber JH Dore ND Wilson JM Devadason SG LeSoëf PN. Inhalation therapy in asthma: Nebulizer or pressurized metered-dose inhaler with holding chamber? In vivo comparison of lung deposition in children.J Pediatr. 1999; 135: 28-33Abstract Full Text Full Text PDF PubMed Scopus (140) Google Scholar although they apparently did not undertake a formal evaluation.These PARI SVNs and MDI + AeroChamber VHC have similar drug delivery efficiency and the potential to provide a therapeutically equivalent dose of bronchodilator more rapidly (simply by administering 1 to 2 additional puffs by MDI at 1- to 2-minute intervals), much less obtrusively, at much lower cost, and without the need to fill the nebulizer with a liquid solution and seek a power supply. It would be surprising if adolescent patients or caregivers of younger children would not opt for aerosol therapy with the much easier to use and maintain, more cost-effective MDI + VHC. Surely, it is only if physicians have a false and scientifically unsupportable notion that nebulizers in some way provide “better” therapy or if no MDI formulation is available (eg, dornase alfa), that they would burden their patients with SVN treatments and the associated paraphernalia. If that is the case, then major education programs must be undertaken if patients and the health care system’s budget are to benefit from advances in aerosol science! See related articles, p. 22 and p. 28. Be not the first by whom the new are tried nor yet the last to lay the old aside.—William Pope In medical practice, despite the increasing acceptance of “evidence-based” therapeutics, the “tried and true” may persist long after the evidence is overwhelmingly in favor of change. The articles by Schuh et al1Schuh S Johnson DW Stephens D Callahan S Winders P Canny GJ. Comparison of albuterol delivered by a metered dose inhaler with spacer versus a nebulizer in children with mild acute asthma.J Pediatr. 1999; 135: 22-27Abstract Full Text Full Text PDF PubMed Scopus (100) Google Scholar in Toronto and by Wildhaber et al2Wildhaber JH Dore ND Wilson JM Devadason SG LeSoëf PN. Inhalation therapy in asthma: Nebulizer or pressurized metered-dose inhaler with holding chamber? In vivo comparison of lung deposition in children.J Pediatr. 1999; 135: 28-33Abstract Full Text Full Text PDF PubMed Scopus (140) Google Scholar in Perth in this issue of The Journal contribute interesting new data and commentary to a debate that has continued unabated for at least 2 decades—the notion that aerosol therapy with bronchodilators for severe exacerbations of asthma or chronic obstructive pulmonary disease should be administered by small-volume nebulizers and that metered-dose inhalers should be reserved for mild to moderate asthma attacks or for maintenance therapy. Development of valved aerosol holding chambers as MDI accessory devices to make MDIs more patient friendly and versatile began about 20 years ago, shortly after spacers were introduced as a means of extending the MDI mouthpiece to reduce aerosol impaction in the mouth and throat. By applying an improved understanding of aerosol physics3Corr D Dolovich M McCormack D Ruffin R Obminski G Newhouse M. Design and characteristics of a portable breath actuated, particle size selective medical aerosol inhaler.J Aerosol Sci. 1982; 13: 1-7Crossref Scopus (72) Google Scholar and receptor sites in the airways,4Barnes PJ. Muscarinic receptors in airways: recent developments.J Appl Physiol. 1990; 68: 1777Crossref PubMed Scopus (7) Google Scholar, 5Barnes PJ Basbaum CB Nadel JA. Autoradiograph localization of autonomic receptors in airway smooth muscle: marked difference between large and small airways.Am Rev Respir Dis. 1983; 127: 758-762PubMed Google Scholar VHCs introduced a new “low tech” paradigm to the therapy of reversible airflow obstruction. These relatively small MDI add-on devices improved pulmonary drug targeting and the efficiency and versatility of MDIs,6Newhouse MT Dolovich MB. Control of asthma by aerosols.N Engl J Med. 1986; 315: 870-874Crossref PubMed Scopus (206) Google Scholar and by taking a “systems” approach with patient- and task-specific accessories, they became capable of supplanting SVNs in clinical settings ranging from bronchopulmonary dysplasia in neonates7Fok TF Monkman S Dolovich M Gray S Coates G Paes B et al.Efficiency of aerosol medical delivery from a metered dose inhaler versus jet nebulizer in infants with bronchopulmonary dysplasia.Pediatr Pulmonol. 1996; 21: 301-309Crossref PubMed Scopus (172) Google Scholar to heaves (asthma) in horses!8Tesarowski DB Viel L McDonnell WN Newhouse MT. The rapid and effective administration of a β2 -agonist to horses with heaves using a compact inhalation device and metered-dose inhalers.Can Vet J. 1994; 35: 170-173PubMed Google Scholar VHCs were initially intended to overcome the fairly common problem of poor hand-breath coordination in adults, and their versatility was gradually augmented by the introduction of masks of various sizes to replace the mouthpiece for treating tidal-breathing infants and children,9Gervais A Begin P. Bronchodilatation with a MDI plus an extension using tidal breathing versus jet nebulization.Chest. 1987; 92: 822-824Crossref PubMed Scopus (17) Google Scholar, 10Ba M Spier S Lapierre G Lamarre A. Wet nebulizer versus spacer and metered dose inhaler via tidal breathing.J Asthma. 1989; 26: 355-358Crossref PubMed Scopus (19) Google Scholar as well as frail older adults and intellectually challenged patients.11Nair LG Diamond R Falcone G Thakore S Fine JM. Fine efficacy of mask spacer with metered dose inhaler in the frail elderly.Chest. 1995; 108: 216sCrossref PubMed Scopus (65) Google Scholar Patients requiring intubation and assisted ventilation could also be treated more efficiently and cost-effectively with MDIs for providing β-agonist and anticholinergic aerosol therapy, as ventilator-compatible accessory devices were developed.12Dhand R Tobin MJ. Inhaled bronchodilator therapy in mechanically ventilated asthma.Am J Respir Crit Care Med. 1997; 156: 3-10Crossref PubMed Scopus (167) Google Scholar As well-designed bronchodilator studies comparing MDI + VHC and SVN in severe acute asthma accumulated, it became evident that the addition of VHCs to MDIs allows the replacement of SVNs even in the most challenging clinical situations,13Newhouse MT. Emergency department management of life-threatening asthma: Are nebulizers obsolete?.Chest. 1993; 103: 661-662Crossref PubMed Scopus (32) Google Scholar with the obvious exception of those in which no MDI formulation is available (eg, dornase alfa, inhaled antibiotics). For administration of aerosol bronchodilators to patients with severe, life-threatening asthma in the emergency department, a recent meta-analysis14Turner MO Patel A Ginsburg S Fitzgerald JM. Bronchodilator delivery in acute airflow obstruction. A meta-analysis.Arch Intern Med. 1997; 157: 1736-1744Crossref PubMed Google Scholar confirmed that MDI + VHC was therapeutically equivalent to SVNs overall but with more rapid rescue,14Turner MO Patel A Ginsburg S Fitzgerald JM. Bronchodilator delivery in acute airflow obstruction. A meta-analysis.Arch Intern Med. 1997; 157: 1736-1744Crossref PubMed Google Scholar, 15Hodder RV Calcutt LE Leach JA. Metered dose inhaler with spacer is superior to wet nebulisation for emergency room treatment of acute, severe asthma [abstract].Chest. 1988; 94: 52SGoogle Scholar fewer side effects,16Lee N Rachelefsky G Kobayashi RH Kobayashi AL Siegel SC Katz RM et al.Comparison of efficacy and safety of albuterol administered by power-driven nebulizer (PND) versus metered dose inhaler (MDI) with Aerochamber and mask in young children with acute asthma [abstract].J Allergy Clin Immunol. 1991; 87: 307Abstract Full Text PDF Google Scholar lower cost per treatment,17Turner MO Gafni A Swan D Fitzgerald JM. A review and economic evaluation of bronchodilator delivery methods in hospitalized patients.Arch Intern Med. 1996; 156: 2113-2118Crossref PubMed Google Scholar and a lower mortality rate in adults with coronary artery disease.18Suissa S Hemmelgarn B Blais L Ernst P. Bronchodilators and acute cardiac death.Am J Respir Crit Care Med. 1996; 154: 1598-1602Crossref PubMed Scopus (125) Google Scholar VHCs provide these benefits by their ability to decrease the oropharyngeal deposition of bronchodilators (or corticosteroids) by 80% to 90% and the total body dose by about 75%, thus improving the therapeutic ratio and drug targeting to the lower respiratory tract.19Dolovich M Ruffin R Corr D Newhouse MT. Clinical evaluation of a simple demand inhalation MDI aerosol delivery device.Chest. 1983; 84: 36-41Crossref PubMed Scopus (130) Google Scholar This is accomplished with lower device and drug costs, while providing much greater portability, freedom from carrying liquid solutions, independence from a power source, and no risk of disseminating infection from contaminated ventilator circuits or poorly serviced SVNs.20Craven DE Lichtenberg DA Goularte TA Make BJ McCabe WR. Contaminated medication nebulizers in mechanical ventilator circuits, Source of bacterial aerosols.Am J Med. 1984; 77: 834-838Abstract Full Text PDF PubMed Scopus (137) Google Scholar, 21Barnes KL Clifford R Holgate ST. Bacterial contamination of home nebulizers.Br Med J (Clin Res Ed). 1987; 295: 812Crossref PubMed Scopus (50) Google Scholar Based on the evidence, it appears that the debate has been resolved in favor of MDI + VHC, although many physicians and especially pediatricians, continue to prescribe SVNs for their patients, not only in hospital practice but for home use as well. Not surprisingly, many patients and caregivers therefore conclude that SVNs are, on balance, the optimum means of providing aerosol therapy for management of acute asthma, especially in children. Nothing could be further from the truth! The articles by Schuh et al1Schuh S Johnson DW Stephens D Callahan S Winders P Canny GJ. Comparison of albuterol delivered by a metered dose inhaler with spacer versus a nebulizer in children with mild acute asthma.J Pediatr. 1999; 135: 22-27Abstract Full Text Full Text PDF PubMed Scopus (100) Google Scholar and Wildhaber et al2Wildhaber JH Dore ND Wilson JM Devadason SG LeSoëf PN. Inhalation therapy in asthma: Nebulizer or pressurized metered-dose inhaler with holding chamber? In vivo comparison of lung deposition in children.J Pediatr. 1999; 135: 28-33Abstract Full Text Full Text PDF PubMed Scopus (140) Google Scholar take opposing sides of the controversy, with the latter presenting arguments, based on total dose and dose administered per minute, in favor of therapy with SVNs. The study by Schuh et al, like most other ED studies, supports the use of MDI + VHC as therapeutically equivalent to SVN in the treatment of asthma. Their double-blind, triple-dummy study further demonstrates that 200 μg of albuterol is therapeutically equivalent to a 0.15 mg/kg body weight adjusted dose of 600 to 1000 μg, an unnecessarily large dose of β-agonist whether delivered by Intec Whisperjet SVN or by AeroChamber MDI + VHC in these mild to moderate acute episodes. Adverse events, even in the high-dose group, were rare and relatively minor. The heart rate was significantly higher in the nebulizer group, possibly because of increased oropharyngeal and/or alveolar deposition, and therefore systemic albuterol absorption, with the SVN in contrast to the VHC.3Corr D Dolovich M McCormack D Ruffin R Obminski G Newhouse M. Design and characteristics of a portable breath actuated, particle size selective medical aerosol inhaler.J Aerosol Sci. 1982; 13: 1-7Crossref Scopus (72) Google Scholar, 19Dolovich M Ruffin R Corr D Newhouse MT. Clinical evaluation of a simple demand inhalation MDI aerosol delivery device.Chest. 1983; 84: 36-41Crossref PubMed Scopus (130) Google Scholar Although there was no significant difference in forced expiratory volume in 1 second between the treatment groups, there was a trend to a greater number of “excellent” responders in the high-dose MDI + VHC group and a greater number of “poor” responders in the SVN group. Perhaps most important with regard to the issue of patient preference and compliance (adherence) was the fact that 90% of the families opted for MDI + VHC for home use. Wildhaber et al2Wildhaber JH Dore ND Wilson JM Devadason SG LeSoëf PN. Inhalation therapy in asthma: Nebulizer or pressurized metered-dose inhaler with holding chamber? In vivo comparison of lung deposition in children.J Pediatr. 1999; 135: 28-33Abstract Full Text Full Text PDF PubMed Scopus (140) Google Scholar—in concluding that the SVN (Pari Boy38/Proneb Turbo and LC Star), which nebulized 2000 μg of salbutamol, was superior to 360 μg by MDI + VHC because it delivered a greater total dose and dose per minute to children’s lungs—create a “straw man.” In the very unlikely event that such a large dose (equivalent to more than 20 puffs of salbutamol by MDI) were clinically indicated, the MDI + VHC could readily provide it with dose titration at the rate of 1 puff every 30 to 60 seconds and could do so more safely and economically. For a therapeutically equivalent dose, not likely to exceed 4 to 6 puffs even in severe acute asthma, 2 to 4 minutes would suffice; and the medication could be administered by the admitting physician or nurse while the history and physical examination are performed. Furthermore, the calculation of Wildhaber et al2Wildhaber JH Dore ND Wilson JM Devadason SG LeSoëf PN. Inhalation therapy in asthma: Nebulizer or pressurized metered-dose inhaler with holding chamber? In vivo comparison of lung deposition in children.J Pediatr. 1999; 135: 28-33Abstract Full Text Full Text PDF PubMed Scopus (140) Google Scholar does not take into account the time required to assemble, disassemble, and clean the SVN, which must be done on each occasion; whereas the MDI nozzle and VHC do not require cleaning more than once a week. Furthermore, there is additional benefit to using the same device in the ED as the patient uses at home for maintenance therapy. It provides an opportunity to review good inhalation technique at a time when the patient or caregiver is particularly motivated, while at the same time delivering a clear message that the MDI + VHC that the child has been prescribed for home use is effective enough for the treatment of even the sickest patients in the hospital.14Turner MO Patel A Ginsburg S Fitzgerald JM. Bronchodilator delivery in acute airflow obstruction. A meta-analysis.Arch Intern Med. 1997; 157: 1736-1744Crossref PubMed Google Scholar, 17Turner MO Gafni A Swan D Fitzgerald JM. A review and economic evaluation of bronchodilator delivery methods in hospitalized patients.Arch Intern Med. 1996; 156: 2113-2118Crossref PubMed Google Scholar, 22Amirav I Newhouse MT. Metered-dose inhaler accessory devices in acute asthma. Efficacy and comparison with nebulizers: a literature review.Arch Pediatr Adolesc Med. 1997; 151: 876-882Crossref PubMed Scopus (83) Google Scholar But are the data of Schuh et al1Schuh S Johnson DW Stephens D Callahan S Winders P Canny GJ. Comparison of albuterol delivered by a metered dose inhaler with spacer versus a nebulizer in children with mild acute asthma.J Pediatr. 1999; 135: 22-27Abstract Full Text Full Text PDF PubMed Scopus (100) Google Scholar generalizable to patients with more severe acute asthma? Two recent literature reviews suggest that they are. In a critical review of acute ED asthma therapy in children, Amirav and Newhouse concluded that MDI + VHC was as effective as SVN for relieving bronchospasm but at a dose, on average, about 6-fold smaller.22Amirav I Newhouse MT. Metered-dose inhaler accessory devices in acute asthma. Efficacy and comparison with nebulizers: a literature review.Arch Pediatr Adolesc Med. 1997; 151: 876-882Crossref PubMed Scopus (83) Google Scholar Turner et al14Turner MO Patel A Ginsburg S Fitzgerald JM. Bronchodilator delivery in acute airflow obstruction. A meta-analysis.Arch Intern Med. 1997; 157: 1736-1744Crossref PubMed Google Scholar arrived at a similar conclusion from their meta-analysis comparing β-agonist therapy delivered by MDI + VHC with that delivered by SVN in adults with severe acute asthma. These authors, in a separate study, also demonstrated the cost-benefit of MDI versus SVN therapy in the ED, confirming results of several previous studies.17Turner MO Gafni A Swan D Fitzgerald JM. A review and economic evaluation of bronchodilator delivery methods in hospitalized patients.Arch Intern Med. 1996; 156: 2113-2118Crossref PubMed Google Scholar With an efficient VHC and fine particle fraction generated by the MDI, the doses needed to reach the plateau of the dose-response curve have generally been much smaller than those usually administered by SVN, which have ranged from 625 to 5000 μg in 2 to 3 mL of normal saline solution. Such large doses probably became commonplace because, in the past, most continuously operating nebulizers were notoriously inefficient (drug delivery efficiency <10%). With the development of more efficient and breath-activated SVNs, this could create a serious safety issue unless the “usual” dose is appropriately reduced. Indeed, it would be surprising if the SVN-delivered doses in the study by Wildhaber et al2Wildhaber JH Dore ND Wilson JM Devadason SG LeSoëf PN. Inhalation therapy in asthma: Nebulizer or pressurized metered-dose inhaler with holding chamber? In vivo comparison of lung deposition in children.J Pediatr. 1999; 135: 28-33Abstract Full Text Full Text PDF PubMed Scopus (140) Google Scholar did not cause tremor and tachycardia in many of their subjects. Standards for SVNs such as lower respiratory tract delivery efficiency are only now being developed by committees of the American and European thoracic societies and are not usually available from the manufacturers. There is considerable variability between (and sometimes even within) SVN models. Physicians should become very familiar with one or two efficient devices for which there is clinical trial support and try to avoid frequent switching based on a smooth sales presentation (frequently with a minimum of clinical data) or price alone. It should be emphasized that the same is true of VHCs, which may vary tremendously in quality, durability, fine-particle aerosol output, mask fit and dead space, inspiratory and expiratory valve resistance, and stiffness from one manufacturer to another. This is particularly true in pediatric practice in which, for example, mask dead space may be as low as 15 mL with inspiratory valve resistance of 0.6 cm H2 O/L/s at 20 L/min in the Aero- Chamber device used by Schuh et al1Schuh S Johnson DW Stephens D Callahan S Winders P Canny GJ. Comparison of albuterol delivered by a metered dose inhaler with spacer versus a nebulizer in children with mild acute asthma.J Pediatr. 1999; 135: 22-27Abstract Full Text Full Text PDF PubMed Scopus (100) Google Scholar and by Wildhaber et al2Wildhaber JH Dore ND Wilson JM Devadason SG LeSoëf PN. Inhalation therapy in asthma: Nebulizer or pressurized metered-dose inhaler with holding chamber? In vivo comparison of lung deposition in children.J Pediatr. 1999; 135: 28-33Abstract Full Text Full Text PDF PubMed Scopus (140) Google Scholar or as high as 50 mL (equivalent to a tidal volume at age 6 months) with valve resistance 2 to 5 times higher with other add-on devices. The radiolabeled salbutamol aerosol deposition study carried out by Wildhaber et al2Wildhaber JH Dore ND Wilson JM Devadason SG LeSoëf PN. Inhalation therapy in asthma: Nebulizer or pressurized metered-dose inhaler with holding chamber? In vivo comparison of lung deposition in children.J Pediatr. 1999; 135: 28-33Abstract Full Text Full Text PDF PubMed Scopus (140) Google Scholar with a static-free AeroChamber VHC brings important laboratory research to the bedside. Their in vitro studies demonstrated the adverse effect of electrostatic charge on the walls of plastic holding chamber devices on drug delivery efficiency and the benefit of simply coating the inside of the VHC with dishwashing detergent. They showed that they could deliver more than twice as much salbutamol aerosol to the lower respiratory tract2Wildhaber JH Dore ND Wilson JM Devadason SG LeSoëf PN. Inhalation therapy in asthma: Nebulizer or pressurized metered-dose inhaler with holding chamber? In vivo comparison of lung deposition in children.J Pediatr. 1999; 135: 28-33Abstract Full Text Full Text PDF PubMed Scopus (140) Google Scholar compared with previous studies in infants and young children.23Tal A Golan H Grauer N Aviram M Albin D Quastel MR. Deposition pattern of radiolabeled salbutamol inhaled from a metered-dose inhaler by means of a spacer with mask in young children with airway obstruction.J Pediatr. 1996; 128: 479-484Abstract Full Text Full Text PDF PubMed Scopus (204) Google Scholar Also of interest is the issue of patient and caregiver preference with regard to the selection of an aerosol delivery system, which was raised by Wildhaber et al,2Wildhaber JH Dore ND Wilson JM Devadason SG LeSoëf PN. Inhalation therapy in asthma: Nebulizer or pressurized metered-dose inhaler with holding chamber? In vivo comparison of lung deposition in children.J Pediatr. 1999; 135: 28-33Abstract Full Text Full Text PDF PubMed Scopus (140) Google Scholar although they apparently did not undertake a formal evaluation. These PARI SVNs and MDI + AeroChamber VHC have similar drug delivery efficiency and the potential to provide a therapeutically equivalent dose of bronchodilator more rapidly (simply by administering 1 to 2 additional puffs by MDI at 1- to 2-minute intervals), much less obtrusively, at much lower cost, and without the need to fill the nebulizer with a liquid solution and seek a power supply. It would be surprising if adolescent patients or caregivers of younger children would not opt for aerosol therapy with the much easier to use and maintain, more cost-effective MDI + VHC. Surely, it is only if physicians have a false and scientifically unsupportable notion that nebulizers in some way provide “better” therapy or if no MDI formulation is available (eg, dornase alfa), that they would burden their patients with SVN treatments and the associated paraphernalia. If that is the case, then major education programs must be undertaken if patients and the health care system’s budget are to benefit from advances in aerosol science!" @default.
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• W2084236663 title "Asthma therapy with aerosols: Are nebulizers obsolete? A continuing controversy" @default.
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