review Spacer Devices Used with Metered-Dose Inhalers* Breakthrough or Gimmick? Peter KOnig, M.D., Ph.D. t

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1 review Spacer Devices Used with Metered-Dose Inhalers* Breakthrough or Gimmick? Peter KOnig, M.D., Ph.D. t In an effort to improve the delivery of a drug to the lungs, to correct problems of hand-lung discoordination, and to reduce local side effects such as oral candidiasis, a number of spacer devices have been developed to attach to metereddose inhalers. Administration of bronchodilator drugs to patients with faulty techniques of inhalation has been improved with the addition of spacers. In adults and older children with a correct technique of inhaling bronchodilators, the spacer devices do not seem to have any advantage over the simple metered-dose inhalers. Young children (two to five years) can benefit from inhaled bronchodilators or corticosteroids by use of spacer devices with one-way valves. Older children and especially adults who suffer from dysphonia or thrush from inhaled corticosteroids can also benefit from spacers. In patients whose condition is well controlled with the usual inhaled doses of corticosteroids with no local side effects, spacer devices show promise, but more studies are needed. Topical administration of adrenergic agents through the inhaled route offers many advantages over the oral route, such as the need to administer smaller doses, a quick onset of action, and fewer side effects. Metered-dose inhalers (MD Is) are the most frequently used funns of administering inhaled bronchodilator drugs and are also widely used fur administration of corticosteroids; however, MDis also create some difficulties. First, they deliver only about 10 percent of the dose to the lungs, with 80 percent deposited in the oropharynx. 1 Oropharyngeal deposition causes increased systemic absorption and, with corticosteroids, 2 an increased risk of local side effects (candidiasis). Secondly, about one-third to one-half of the patients use an improper technique of inhalation (hand-lung discoordination), 3-.5 and about 14 to 16 percent are unable to learn even after careful tuition. 6 7 The use of a spacer fitted to the mouthpiece of a conventional MDI has been suggested to overcome the problems of poor coordination and oropharyngeal deposition. It was thought that by lengthening the distance between the actuator and mouth, the aerosol jet would be slowed down and therefore cause less impaction in the oropharynx. The evaporation of solvent would decrease the size of particles, facilitating greater deposition in the lungs and perhaps better penetration to peripheral airways. It was also hoped that the spacers would reduce problems of coordination, principally by causing a delay between actuation *From the Department of Child Health, Hospital and Clinics, University of Missouri, Columbia. tprofessor of Child Health. Ref>rint requests: Dr. Konig, Child Health, University of Missouri, Columbia and inhalation, but also because the sudden cooling effect of the freon jet hitting the oropharyngeal mucosa makes some patients stop their inhalation. 8 Most studies used either tube spacers, with a volume of about 80 ml, or cone-shaped (or pear-shaped) spacers with volumes of approximately 700 ml (Fig 1), although other experimental devices have been used in a few studies. This review summarizes some recent studies evaluating the effect of spacer devices on delivery of the drug. B c A FIGURE 1. A, Metered-dose inhaler with tube B, MDI with cone-shaped and C, MDI with pear-shaped spacer. Spacer Devices Used wtlh Metenlckb9e Inhalers (Peter Konig)

2 Table 1-Sttuliea cf Depofttion cf Drugs Method Design of No. of Age, Drugs and of Spacer Reference Study Patients yr Dosage Delivery Design Effectiveness Dolovich et a Freon 12/114 and MDI; Thbe Deposition in lung same (1983) re spacer (Aerochamber) in normal and COPD subjects with and without deposition in throat decreased by >90 percent in both groups Newman et al 10 Single dose 10 Adults 6 doses of Teflon MDI; Thbe or cone Spacers reduced oral (1981) particles in spacer deposition; cone chlorofluorocarbon propellants increased total pulmonary deposition Moren" (1978) Cumulative-dose 9 Adults 8 doses of 250jl.g of terbutaline MDI; Thbe or pear spacer Spacers significantly reduced oral deposition STUDIES of DRuG DErosmoN The effects of various spacers on deposition of aerosols in the mouth and airways was investigated in three s t u d i (Table e s ~ u 1). Dolovich and associates 9 round that the attachment of a tube spacer (Aerochamber) to an MDI reduced pharyngeal deposition of aerosoll4-rold, but delivery of aerosol to intrapulmonary airways in normal subjects and patients with chronic bronchitis remained unchanged. In a group of nine patients with stable asthma, inhalation of fenoterol (0.4 mg) using the tube spacer (Aerochamber) achieved effective bronchodilation similar to an optimally administered MDI. In another study, 10 ten subjects with obstructive airway disease inhaled the aerosol with radioactive labelled particles of polytetrafiuoroethylene (Teflon) in a controlled manner from a conventional actuator alone or in combination with a tube or a cone spacer. Distribution of radioaerosol was measured using a whole-body counter (Shadowshield). Deposition on the conducting airways was significantly improved by both spacers, but alveolar deposition was unchanged. Total pulmonary deposition was 7.8 percent, U.S percent, and 13.0 percent of the dose with the MDI, tube spacer, and cone spacer, respectively. Only the cone spacer was significantly better than the MDI in this respect. Initial oropharyngeal deposition was reduced by both spacers in all ten patients. Morenu round that deposition of terbutaline in the mouth was significantly reduced by use of a spacer. He also concluded that the availability of the drug to the airways was increased. SPACERS AND HAND-LUNG DISCOORDINATION Several studies have investigated the efficacy of spacer devices in subjects with poor hand-lung coordination (Table 2). ~ 1 Godden 6 and Crompton 12 studied 22 adult patients with problems of hand-lung coordination and concluded that bronchodilation was significantly better when the drug was administered with an a tube spacer than with the MDI alone; however, in 13 asthmatic adults with incorrect technique, Epstein and collaborators 13 round no difference in bronchodilation when the drug was self-adminis- Table 2-Studtu Comparing Efficacrl cf Bronclwdilator Drugs Administered by MDI Alone or MDI with Spacer Dmce in Adults with Poor Hand-Lung Coordination Method Design of No. of Age, Drugs and of Spacer Reference Study Patients yr Dosage Delivery Design Effectiveness Godden and Crompton 11 Single-dose, open, ~ ~ o g o MDI; f Thbe Spacer> MDI (1981) terbutaline spacer Epstein et al 13 (1983) Single-dose, 13 Mean, jl.gof MDI; Thbe MDI=spacer double-blind fenoterol spacer (Aerochamber) and placebo Hidinger and Perk 14 Single-dose, open, ~ ~ o g o MDI; f Thbe Spacer>MDI (1981) terbutaline spacer at5 min, 4 hr Stauder and Hidinger'" Single-dose, open, ~ ~ o g o MDI; f Thbe MDI=spacer (1980) terbutaline spacer Bloomfield and Crossover ~ ~ o g o MDI; f Thbe MDI=spacer Crompton'" (1979) terbutaline spacer CHEST I 88 I 2 I AUGUST, 1985 m

3 'lllble 3-Studia CornpGring EJJico.crl t/brondtodllmor ljrugl Adminimred by MDI Alone or MDI with S,_,- DeW:. in Adullt with AallamG or Chronic Obatruclice AinDGfl DiNtue Design of No. of Age, Drugs and Method of Spacer lleference Study Patients yr Dosage Delivery Design Efl'ectivenesst Dolovich et al' Single-dose, g j.Lg of fenoterol MDI; Tube MDI=spacer (1983) double-blind, and placebo spacer (Aerochamber) Langaker and Long-term j.Lg of MDI; Tube Spacer>MDI Hidingerl 1 (1982) (3-wk), open, terbutaline as spacer needed Spicer et al" (1980) Long-term 33 Mean, j.Lg of MDI; Tube Spacer<!:MDI (only (4-wk), open, terbutaline spacer PEFR twice daily signillcant) Dorow and 2-day, double j.Lg of MDI; Thbe Spacer<!:MDI (only Hidingerl 1 (1982) blind, terbutaline and spacer Raw and CV placebo signillcant) Pauwels et al 15 (1984) Cumulative j.Lg-750j.Lg MDI; Thbe Spacer<!: MDI dose, double- ( = 1,5001J.g) of spacer (some measures blind, terbutaline of function of small airways signillcant) Hidinger and Long-term j.Lg of MDI; Spacer>MDI ( 1984) (4-wk), terbutaline spacer Lulling et al 15 (1983) Crossover j.Lg of MDI; Thbe; pear Spacers> MDI terbutaline spacer D o r o w " ~ I.Jndgrenetal 15 Cumulative j.Lg-750j.Lg MDI; Thbe; pear Spacers> MDI (1980) dose, ( = 1,5001J.g) of spacer terbutaline Cusbley et al" (1983) Cumulative j.Lg-1,0001J.g MDI; Spacer>MDI dose, double- (=4,000j.Lg) blind, Eriksson et al 15 Single-dose, j.Lg of Tube MDI (albuterol) (1980) double-blind, terbutaline, spacer =spacer 200j.Lg of (terbutaline) albuterol and MDI placebo Gomm et a] (1980) Cumulative j.Lg-250j.Lg MDI; Thbe MDI=spacer dose, double- (=500j.Lg) of spacer blind, terbutaline at 20-min intervals I.Jndgren and Cumulative j.Lg-12,000j.Lg MDI; MDI=spacer Larsson 11 (1982) dose, open, ( = 23,300j.Lg) of spacer terbutaline Munch et a] (1983) Cumulative j.Lg-250j.Lg MDI; MDI=spacer dose, open, (=500j.Lg)of spacer terbutaline and placebo Dirksen (1983) Cumulative j.Lg-200j.Lg of MDI; Thbe MDI=spacer dose, double- fenoterol spacer (Aerochamber) blind, Poppiur'l (1980) Cumulative j.Lg-750j.Lg MDI; Tube MDI=spacer dose, ( = 1,2501J.g) of spacer terbutaline Pedersen and Single-dose, ,0001J.g of MDI; MDI=spacer Bundgaard 31 (1983) terbutaline ; and IPPV Bundgaard 31 (1982) Single-dose, 13 Adults 1,0001J.g of MDI; MDI=spacer terbutaline both as ; bronchodilator and prevention *IPPY, Intermittent positive-pressure ventilation. and IPPV ofeia tpefr, Peak expiratory ftow rate; Raw, airway resistance; CV, closing volume; and EIA, exercise-induced asthma. 278 Spacer Oelllces Used with Melelacktoee Inhalers (Peter Konig)

4 tered using an MDI with the patients own (faulty) technique, an MDI administered by a trained staff member, or tube spacer (Aerochamber). A number of studies mimicked faulty techniques of inhalation by delaying inhalation by two seconds after actuation of the inhaler. Some of these studies showed that if delayed inhalation was used with an MDI alone and an MDI with a tube spacer, the latter method was superior, 14 while other studies demonstrated that if the delay was only used with the MDI with spacer and the MDI alone was given correctly, the degree of bronchodilation was equal, showing that the spacer can correct problems of coordination. SPACERS IN ADUU'S WITHOUT PREVIOUSLY KNOWN DISCOORDINATION Studies conducted in adults with asthma or chronic obstructive airway disease are outlined in Thble 3. These studies 9 17.,') 2 were all design and ranged from a single dose to long-term administration (three to fuur weeks). The drugs administered were terbutaline, fenoterol, albuterol, and metaproterenol. A variety of designs for the spacer were employed. Of the 17 studies listed, eighf 7 24 reported somewhat better effects on airway functioning when a spacer device was whether the difference is clinically relevant. Lulling and associates 22 noted that the difference between the spacer and an MDI was of the magnitude of about 3 to 7 percent, which they did not consider clinically relevant. SPACERS IN CHILDREN Several studies on the effectiveness of MDis with spacers are summarized in Table Four reports33-36 stated that delivery of terbutaline or fenoterol with an MDI with a spacer device was more effective in children with asthma than was delivery with the MDI alone. Ellul-Micallef and associates 33 studied effects of terbutaline administered to 12 children with extrinsic bronchial asthma. The spacer device employed was a collapsible tube (slightly conical). Both the aerosol alone and the aerosol with spacer significantly improved peak expiratory flow from baseline values, and the value for the aerosol with the spacer was significantly higher than that with the aerosol only at 20 and 60 minutes after therapy. Similar results were reported by Kjellman and Hidinger-'14 in 18 children with bronchial asthma, and by Pedersen 35 and by Rivlin and co-workers 36 in 20 and 10 children with acute bronchoconstriction, respectively. used. The remaining nine p u b l i c a treported i o n s g - ~ Four other studies reported that bronchodilator no significant differences in efficacy between delivery drugs (fenoterol or terbutaline) were equally effective with an MDI alone or an MDI with a spacer. when given to children by MDI alone or with a spacer. It is not clear to what extent the favorable results fur Van Asperen et al 37 measured change in the forced spacers in some studies are due to some of the patients expiratory volume in one second in seven asthmatic not having good hand-lung coordination. In some of children following administration of soo...,g of terbutaline with an MDI or an MDI with a tube spacer these studies, it is stated that some of the patients used faulty technique, 17 while in other studies, insufficient with a five-second delay between actuation and inhalation. No significant differences were fuund in bron or no data are given about the technique of inhalation. 20 Although some studies showed a statistically significant difference in favor of spacers, the question arises Hodges and associates 39 measured peak expiratory chodilation between the two methods of delivery. flow Table 4-Studiea Comparing EJ]icacy cf Bronchodilator Drugt Adminiltered by MDI Alone or MDI with Spacer Device i11 ClailJnm tditla Altlama Design of No. of Age, Drugs and Method of Spacer Reference Study Patients yr Dosage Delivery Design Effectiveness Ellul-Micallef Single-dose, J.Lg of terbutaline MDI; Collapsible cone Spacer>MDI et al 33 (1980) spacer Kjellrnan and Single-dose, open, J.Lg of terbutaline MDI; Collapsible cone Spacer>MDI Hidinger" (1981) spacer Pedersen 35 (1983) Single-dose, double J.Lg of terbutaline MDI; Tube Spacer>MDI blind, and placebo spacer Rivlin et al 38 (1984} Single-dose, double g of fenoterol MDI; Spacer> MDI blind, and Van Asperen et al"' Single-dose, J.Lg of terbutaline MDI; Thbe MDI=spacer (1981} spacer Gurwitz et al 38 Single-dose, double- 12 Mean, g of fenoterol MDI; Thbe MDI=spacer (1983) blind, and placebo spacer (Aerochamber) Hodges et al"" Single-dose, double g of fenoterol MDI; Tube MDI=spacer (1981) blind, and placebo spacer (Aerochamber} Oliver et al 40 (1982} Single-dose, double J.Lg of terbutaline MDI; Tube MDI=spacer blind, and placebo spacer CHEST I 88 I 2 I AUGUST,

5 in ten children following administration of 0.4 mg of fenoterol and placebo by a standard aerosol inhaler or by inhaler with an attached tube spacer (Aerochamber). Two of the children had significantly higher peak expiratory ftow when the active drug was administered with the tube spacer, and two children had significantly better results using the standard inhaler, while in the remaining six children, no significant differences were observed. Eight out of ten children patients with the most faulty technique were eliminated from the analyses, the difference between the the spacer was no longer significant. It seems, therefore, that the favorable results for spacers in some studies are at least in part due to inclusion of patients with poor technique. TUBE VS CONE (OR PEAR) SHAPED SPACERS Lindgren and associatesll3 compared the efficacy of favored the tube spacer (Aerochamber), and one fa- tube and cone-shaped spacers with terbutaline (0.25, vored the conventional inhaler. 0.5, and mg) administered to 18 asthmatic adults. In a similar study, Oliver et al 40 administered ter- These investigators concluded that the pear-shaped butaline by a standard inhaler or an inhaler with a spacer was significantly better than the tube. On the spacer to 15 children under seven years of age and other hand, Lulling and co-workers 22 could not show without prior experience with pressurized aerosol any difference between spacers in 12 asthmatic adults therapy. No difference in the effects of the methods given 0.5 mg of terbutaline with a pear-shaped spacer was observed during the first hour following adminis- or tube. In addition to the cone-shaped or tube tration of the drug. spacers, other designs were tried in an effort to One of the problems with interpreting the results of improve portability and technique of inhalation. Thus, some of these studies is that the adequacy of the Tobin and associates used a collapsible bag with a inhaling technique with the MDI was poor in some noise-making device that warned the patient when the 3 5 p a t i and e n in ~ some reports was not properly inspiratory ftow was too fast. F r e i described g a n ~ a described. 34 Thus, Ellul-Micallef and associates 33 plastic reservoir with a one-way valve and a face mask noted that the great majority of patients had problems suitable for young children. Other improvised devices of technique, and Pedersen 35 commented that if six have been advocated, such as cardboard mouthpieces Table 5-Comparilon8 toith ~ toith Nebulizer Design of ~ r e n e e Study Cushley et ajim (1983) Cumulative-dose, double-blind, Pedersen and 4-way Bundgaarcf' (1983) Madsen et are (1982) Cumulative-dose, single-blind, Morgan et al 41 (1982) Cumulative-dose O'Reilly et al 41 (1983) Cumulative-dose, open, Prior et are (1982) Stauder and HidingerBO (1983) Long-term ( 2 - open, w k ~ Single-dose, open, Laursen et al 51 (1983) Long-term (4-wk), doubleblind, No. of Patients Age, yr Drugs and Dosage Method of Spacer Delivery Design Elfectiveness 16 Adults 3 1 ~ ~, o0g0-0 4~ of ~ terbutaline o g MDI; Spacer> MDI= Adults 1, or ~ 4,0001J.g ~ o g of terbutaline 3() ~ + ~ 1o 2g 5 ~ + ~ 250J.Lg o g by MDI; 1,250J.Lg+ 1,250J.Lg+2,500J.Lg of terbutaline nebulized ,000J.Lg of terbutaline nebulized and 2x 2,000J.Lg of terbutaline by 400J.Lg of terbutaline by spacer + 2X 2,000J.Lg of terbutaline nebulized ~ 1,000J.Lg+ ~ o g + 2, ~, 0~ 0o0 g ~ of + ~ 4o g terbutaline , of ~ terbutaline ~ o g , ofterbutaline ~ ~ o g by MDI; 4,000J.Lg of terbutaline by ,5001J.g of terbutaline by 5, OOOJ.Lg of terbutaline by MDI; spacer 1 mg spacer= 1 mg MDI=nebulized 4 mg >nebulized 1 mg Nebulizer>spacer ; and IPPB Thbe Spacer= Spacer=IPPB= Spacer= Spacer= Spacer= 280 gp_. OeYtces U88d with Meterecklole Inhalers (Peter Konig)

6 used for spirometry, 43 without objective proof that they actually help. Until such topics as electrostatic forces that can deposit large amounts of aerosol particles on the walls of the spacer are better studied, such improvised devices should be considered of uncertain efficacy; however, some such improvisations were shown to be effective. Henry and co-workers," in a controlled trial, demonstrated the efficacy of a device made of a disposable coffee cup applied to the childs face through which a hole was made for the MDI. Lee and Evans 45 successfully used a plastic freezer bag with zipper in children three to six years old. SPACERS CoMPARED WITH NEBULIZERS Several studies & have compared the efficacy of administration ofterbutaline by an MDI with a spacer or by with or without equipment for intermittent positive-pressure breathing {Table 5). Normal adults and patients with asthmatic conditions ranging from stable to severe acute or chronic asthma were tested. All of the studies report that delivery by aerosol with a spacer is as effective or better than delivery by. Furthermore, many of the authors believed that use of an MDI with a spacer is a simple, less expensive, and effective alternative to a. There are a number of problems in correctly interpreting these data. Only one of the studies was performed in patients with severe acute a t t a c k s, ~ which represent one of the main indications for use of a ; the majority of the studies excluded patients with severe obstruction ~ Cushley and associates24 noted that the became better than the MDI as the degree of obstruction increased. Secondly, all of the studies were in adults, while s are used more frequently at home by small children. Thirdly, the doses used varied widely, with some studies giving the same doses by both methods and others using 1:4 or even 1:10 ratio between MDI plus spacer and. SPACERS AND INHALED CORTICOSTEROIDS The number of studies on the use of spacers with inhaled corticosteroids is much smaller than those on bronchodilator drugs. As one might suspect, spacers can help reduce topical side effects such as thrush and dysphonia in patients who have such problems '1 Regarding efficacy, only one study made a direct comparison of the same drug with and without spacer. Toogood and associates 53 treated 35 adults with 400.,a.g and 1, 600.,a.g of budesonide daily and concluded that therapeutic potency doubled with the spacers (both tube and cone); however, at 1,600.,a.glday the administration by spacers caused more systemic side effects, such as decreased morning cortisol levels and increased neutrophilia, probably because of greater absorption from alveoli and distal airways. In a study by Bjorkander and co-workers, s. no direct comparison of an MDI vs spacer is made with the same drug, but there is some suggestion of the usefulness of the tube spacer because beclomethasone (100.,a.g four times daily) by MDI was equally effective as budesonide (SO.,a.g four times daily) when given by MD I, while the same dose of budesonide was better than beclomethasone when given by spacer. Freigang, 42 in an interesting but uncontrolled study, used a plastic aerosol reservoir with a one-way valve and claimed good results in 80 children, some of them as young as one year of age. Willey and associates 55 compared the efficacy of budesonide (200.,a.g twice daily) administered with a tube spacer with that of beclomethasone (100.,a.g four times daily) for one month in 30 adults with asthma and found no difference; however, as two different drugs were used, it is impossible to draw any conclusions about the usefulness of the spacer in this study. The administration of drugs through spacer devices is not entirely free of technical problems. Thus, Pedersen and Ostergaard 56 found that 20 to 63 percent of children failed to derive benefit from terbutaline administered through a tube spacer despite careful instruction. The cause was mostly nasal inhalation, which was correctable in most cases. Cox and associates57 described a case in which the cone spacer became ineffective when dyspnea increased and flow rate fell below a certain level, because the valve could not be closed, and aerosol was being lost to the exterior. They recommended holding the spacer pointing downward at a 45 angle to avoid this particular problem. Even though spacers are designed to reduce problems of coordination, the patients still have to be carefully instructed in the correct technique of inhalation. This is a slow deep inspiration with a ten-second breath-holding for devices without a one-way valve, a technique similar to that recommended with MD Is. 58 For devices with a one-way valve, in small children, slow tidal breathing (three to four breaths for each pufl) can be used. As shown by the fairly large number of articles on spacers, considerable attention has been given to the subject in the last few years. Unfortunately, some of the most important questions are still unanswered. The ideal design of a spacer has not been determined, and it is possible that different designs will be necessary for different indications (less oropharyngeal deposition in patients with candidiasis on inhaled corticosteroids; better pulmonary deposition in patients whose condition is poorly controlled with inhaled bronchodilators or corticosteroids; problems of inhalation in young children or adults with difficulties in coordination). Insufficient research has been done on pulmonary CHEST I 88 I 2 I AUGUST,

7 Table 6-Spocer Dmca Commerciallg Available in United Stotea Clinical'IHals Compared with MDI Pulmonary Brand Name Description Deposition Aerochamber Thbe spacer with one-way valve Not >MDr Inspir Ease Inhal-Aid Azmacort (triamcinolone) Brethancer Collapsible plastic reservoir; regulates inspiratory ftow Cone-shaped; one-way valve; device fur regulating inspiratory ftow Collapsible tube Collapsible tube *In patients with good technique fur MDI. tfour of ten patients in study had poor coordination. 41 *Only one abstract published on subject. 51 Not known Not known Not known >MDI 10 deposition with different drugs using different spacers. There are differences in vapor pressure, metering volume, and particle size between different MD Is, and each of these factors can in8uence penetration of the drug to the lungs; therefore, results of a certain drug with a certain spacer do not necessarily apply to other drugs. Although a fair number of spacers are already available in the United States (Table 6), knowledge about pulmonary deposition and efficacy with different drugs is scarce Instead of more spacers, we need more basic research. It is not easy to explain the controversial results of some studies. In studies of efficacy, insufficient attention has been given to the correct technique of inhalation, and only a few studies controlled these factors. 'D-4' This is one possible explanation fur some conflicting reports. Another factor that was generally neglected was the dose-response curve of drugs. A slight increase in pulmonary deposition may not be reflected in better clinical response at the flat portion of the dose-response curve of that particular drug. Also, most studies with bronchodilator drugs used measurements of forced expiration (spirometry; flow volumes) which can induce dynamic compression of airways in some patients, 5 thereby lessening the bronchodilator effect. SuMMARY AND CuNICAL GuiDEUNES In conclusion, it seems that spacer devices are neither a breakthrough of such magnitude that their use should be made mandatory fur all users of MD Is nor a useless gimmick, but they definitely have a value somewhere between these extremes. For older children and adults with an adequate technique of inhalation, spacers do not seem to improve the effect of bronchodilator drugs, a conclusion shared by other review articles. 80 In patients with problems of coordination, cone-shaped and pear-shaped spacers (eg, Inhal-Aid) might be more effective but are rather bulky Bronchodilators* Corticosteroids Manufacturer Equal efficacy with Not known; possibly Monaghan MD r. uue less efficacy* Efficacy possibly better Not known Key Pharmaceuticals than MDit Not known Not known Key Pharmaceuticals Not known Not known W. H. Rorer, Inc. Greater efficacy"' Geigy and not so portable as tube spacers. In young children (two to five years), spacers with a one-way valve (eg, Aerochamber) can be useful. For administration of inhaled corticosteroids, spacers are indicated in patients with problems of coordination, in those who develop oral candidiasis or dysphonia, and in young children unable to use the ordinary MDI. Whether patients with adequate technique and no side effects would significantly benefit is not clear, because the studies available at the moment, although very promising, used budesonide, which is not yet available in the United States. More studies are needed with some of the inhaled corticosteroids that are available before the practical value of spacers can be better assessed. The possible systemic side effects of inhaled corticosteroids with spacers have not been investigated in children, and there is some evidence that systemic absorption might be greater than with MD Is. 53 TherefOre, in my pediatric practice, the indications fur spacers with inhaled corticosteroids are limited to patients in whom the only alternative would be systemic corticosteroids, such as those too young to use MDis and whose condition is not controlled by bronchodilator drugs or cromolyn, or older patients in whom nonsteroidal drugs plus large doses ofbeclomethasone (800J.Lg to l,oooj.lg) by MDI fail to control their asthma. REFERENCES 1 Newman S, Pavia D, Moren F, Sheahan NF, Clarke SW. Deposition of pressurised aerosols in the human respiratory tract. Thorax 1981; 36: Toogoood JH, jennings B, Greenway RW, Chuang L. Candidiasis and dysphonia complicating beclomethasone treatment of asthma. J Allergy Clin Immunol1980; 65: Coady TJ, Stewart CJ, Davies HJ. Synchronization of bronchodilator release. Practitioner 1976; 217: Orehek J, Gayrard P, Grimaud CH, Charpin J. Patient error in use of bronchodilator metered aerosols. Br Med J 1976; 1:76 5 Saunders KB. Misuse of inhaled bronchodilator agents. Br Med J 1965; 1:

8 6 Paterson IC, Crompton GK. Use of pressurised aerosols by asthmatic patients. Br Med J 1976; 1: Appel D. Faulty use of canister s for asthma. J Family Prac 1982; 14: Crompton GK. Inhalation devices. Eur J Respir Dis 1982; 63: Dolovich M, Eng P, Ruffin R, Corr D, Newhouse MT. Clinical evaluation of a simple demand inhalation MDI aerosol delivery device. Chest 1983; 84: Newman SP, Moren F, Pavia D, Little F, Clarke SW. Deposition of pressurized suspension aerosols inhaled through extension devices. Am Rev Respir Dis 1981; 124: Moren F. Drug deposition of pressurized inhalation aerosols: 1. influence of actuator tube design. Int J Phann 1978; 1: Godden DJ, Crompton GK. An objective assessment of the tube spacer in patients unable to use a conventional pressurized aerosol efficiently. Br] Dis Chest 1981; 75:16.':H58 13 Epstein SW, Parsons JE, Corey PN, Worsley GH, Reilly PA. A comparison of three means of pressurized aerosol inhaler use. 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