comparison of powder and aerosol formulations of salmeterol in the treatment of asthma

Comparison of powder and aerosol formulationsof salmeterol in the treatment of asthmaJames Wolfe, MD*; Stephen Kreitzer, MD†; Paul Chervinsky, MD‡; Michael Lawrence, MD§;Yonghua Wang, PhD¶; Donna Reilly, BS¶; Suzanne Davis, BA¶; and Edmundo Stahl, MD¶

Background: The efficacy and safety of the aerosol metered-dose inhaler (MDI)formulation of salmeterol for asthma symptoms have been established. Recently,salmeterol has been introduced as a micronized powder formulation administeredvia a breath-activated multidose powder inhaler (Diskus).Objective: A multicenter, randomized, double-blind, double-dummy, parallel-

group, placebo-controlled study involving 498 adolescents and adults with mild-to-moderate asthma was conducted to compare the efficacy and safety of salmeterolpowder 50 �g twice daily via Diskus, salmeterol aerosol 42 �g twice daily via MDI,and placebo.Methods: Patients were randomized to one of the three treatment groups for 12

weeks. Efficacy was assessed by serial measurements of forced expiratory volumein one second (FEV1) over 12 hours, daily peak expiratory flow (PEF), self-ratedasthma symptom scores, nighttime awakenings, and supplemental albuterol use.Safety of each treatment was evaluated by monitoring vital signs, electrocardio-grams, Holter monitoring, and occurrence of adverse events.Results: As compared with placebo, both salmeterol powder and aerosol pro-

duced significant improvement in FEV1 and PEF and decreased nighttime awaken-ings and supplemental albuterol use. There were no significant differences in theefficacy of the two salmeterol formulations. The magnitude of improvement inpulmonary function was undiminished over the 12-week study. Both formulationsof salmeterol were well tolerated, with safety profiles not significantly differentfrom placebo.Conclusion: Results of this study indicate that salmeterol, administered either as

a powder 50 �g twice daily via Diskus or as an aerosol 42 �g twice daily via MDI,produces clinically significant and comparable improvement in pulmonary functionand is well tolerated in patients with mild-to-moderate persistent asthma.

Ann Allergy Asthma Immunol 2000;84:334–340.

INTRODUCTIONBeta2-sympathomimetic agonists (�2-agonists) have been prescribed for thecontrol of asthma symptoms for over

30 years. Most of these agents have ashort duration of action, making fre-quent administration necessary. Re-cently, a longer-acting �2-agonist, sal-meterol xinafoate, has made possible atwice-daily dosing frequency. Single-dose studies have shown that salmet-erol has a longer duration of actionthan albuterol and is still effective rel-ative to placebo 12 hours after admin-istration.1 Extensive data from adoles-cent and adult patients participating inwell-controlled trials have establishedthe efficacy and safety of the aerosolmetered-dose inhaler (MDI) formula-tion of salmeterol for improving pul-monary function and asthma symp-toms.2–9

In contrast to previous reports sug-gesting that continuous use of �-ago-nists may lead to diminished control ofasthma,10 adverse events,11 and de-creased bronchodilator effects,12 con-trolled clinical studies with salmeterolhave shown continued asthma controlwith chronic dosing. Clinical trialscomparing salmeterol MDI twicedaily, albuterol four times daily, andplacebo plus as-needed albuterol haveshown that salmeterol provides im-proved symptom control and lungfunction over 12 weeks of therapy.2,3 Ayearlong study4 has also shown thattwice-daily salmeterol MDI improvedsymptom control and spirometric indi-ces compared with albuterol four timesdaily. In addition, the administration ofanti-inflammatory treatment concur-rently with long-acting beta2-agonistsis recommended by the NationalAsthma Education and Prevention Pro-gram guidelines published in 1997.13For symptomatic patients on lowerdoses of inhaled steroids, the additionof salmeterol, compared with increas-ing the dose of inhaled steroids, is as-sociated with significantly greater im-provement in symptom control andlung function.8,14–16 Salmeterol waswell tolerated in these studies.Recently, salmeterol has been intro-

duced as a micronized powder formu-lation administered via Diskus, abreath-activated multidose powder in-haler. The Diskus provides a means ofdelivering salmeterol without the needto coordinate the actuation and inspira-tory efforts associated with the MDI.The ease of use of the Diskus and thedose counter in the Diskus device pro-vide more convenience for patientswith persistent asthma. The Diskus de-vice has been shown to deliver a con-sistent dose irrespective of the flow

* Allergy and Asthma Associates of SantaClara Valley Research Center, San Jose, California.† TMRA, Inc., Tampa, Florida.‡ New England Research Center, North Dart-

mouth, Massachusetts.§ Asthma & Allergy Physicians, Taunton,

Massachusetts.¶ Glaxo Wellcome Inc., Research Triangle

Park, North Carolina.This study was supported by a grant from

Glaxo Wellcome Inc., Research Triangle Park,North Carolina.Received for publication May 29, 1999.Accepted for publication in revised form Oc-

tober 2, 1999.

334 ANNALS OF ALLERGY, ASTHMA, & IMMUNOLOGY

rate in patients with severe obstructivelung disease (% predicted FEV1 of20% to 30%).17 Chlorofluorocarbon re-lease and its subsequent deleterious en-vironmental effects are also avertedwith the Diskus delivery system. Withthe availability of this new powder de-livery system, it is critical to assess thecomparability of the Diskus with themore commonly used MDI system.This study is the first large-scale,

placebo-controlled evaluation of thesafety and efficacy of salmeterol pow-der via the Diskus device and its com-parability to the aerosol formulation.

METHODSPatient SelectionPatient eligibility was assessed at theinitial screening visit, and includedmedical history, physical examination,12-lead electrocardiogram (ECG), spi-rometry, and assessment of bronchodi-lator responsiveness to albuterol. Eli-gible patients were �12 years of agewith a �6-month history of mild-to-moderate asthma (American ThoracicSociety criteria)18 that required phar-macotherapy. At the screening visit,patients were required to have a base-line forced expiratory volume in 1 sec-ond (FEV1) of 50% to 85% of thepredicted normal value after abstainingfrom asthma medications and to dem-onstrate �15% reversibility of airwayobstruction within 30 minutes follow-ing two actuations of albuterol aerosol(180 �g). Furthermore, on treatmentday 1, approximately within 2 weeksafter the screening visit, patients had todemonstrate reproducible lung func-tion within 15% of the best screeningvisit pre-albuterol FEV1, and within50% to 85% of the predicted normalvalue. Predicted normal FEV1 valueswere obtained from Polgar19 for pa-tients 12 to 17 years old and fromCrapo20 for patients �18 years old.Patients on a stable regimen of inhaledor intranasal corticosteroids, cromolyn,or nedocromil were allowed to partic-ipate provided the regimen had begunat least 1 month before screening andremained constant throughout the

study. All other asthma medicationswere prohibited.Patients with upper or lower respi-

ratory tract or middle ear infectionswithin 6 weeks of study entry or withevidence of pulmonary abnormalitiesunrelated to asthma were excluded. Pa-tients must have had less than a 10-pack year history of smoking, must nothave smoked within one year prior tostudy entry, and must not have beenregularly exposed to secondary to-bacco smoke (�4 hours/day). Patientsalso were excluded from the study ifthey presented with a clinically signif-icant concurrent disease.Study Design and ProceduresThis multicenter, randomized, double-blind, double-dummy, parallel-group,placebo-controlled clinical trial wasconducted at 27 centers in the UnitedStates and was approved by an Inves-tigational Review Board. Informedwritten consent was obtained from allparticipants. The study duration was12 weeks. Eligible patients were ran-domly assigned to one of the followingthree treatment regimens: salmeterolpowder 50 �g (one inhalation) BID,salmeterol MDI aerosol 42 �g (twoinhalations) BID, or placebo. Patientsbegan study medication within 2weeks of the screening visit. To main-tain a double-dummy design, all pa-tients received both a MDI and a Dis-kus device and were instructed to useboth at the morning and evening treat-ment times. Supplemental albuterolaerosol MDI was provided to all pa-tients in all groups to control break-through asthma symptoms.Efficacy MeasuresEfficacy was determined by measuring12-hour serial FEV1 on treatment day1, week 4, and week 12, daily peakexpiratory flow (PEF), self-ratedasthma symptoms, days without symp-toms, frequency of nighttime awaken-ings, and supplemental albuterol use.Pulmonary function was assessed at

clinic visits with calibrated spirometryequipment that met or exceeded theminimal performance recommenda-tions of the American Thoracic Soci-

ety.18 The FEV1 value recorded at eachevaluation was the highest FEV1 read-ing obtained from triplicate spirometrydeterminations performed with the pa-tient in the same sitting or standingposition. Serial FEV1 assessments weremade at 30 minutes predose, immedi-ately predose, at 0.5 and 1 hours post-dose, and at subsequent 2-hour intervalsfrom 2 to 12 hours postdose on treatmentday 1, at week 4, and at week 12.Pulmonary function was assessed

daily using a hand-held Mini-Wrightflow meter (Clement Clark, Inc., Lon-don, England). Measurement of PEFwas performed immediately upon ris-ing in the morning before morning ad-ministration of study drug (AM PEF).Patients made triplicate determinationsand recorded the highest value.SafetyThe safety of each treatment was as-sessed by monitoring clinical adverseevents (number and frequency), vitalsigns (pulse, systolic and diastolicblood pressure), physical examina-tions, and 12-lead ECGs. Holter mon-itoring was performed at selected sitesat the screening visit, at treatment day1, and at either treatment week 12 or atthe discontinuation visit if the patientwithdrew early from the study. As anadditional safety precaution, patientswere instructed to call their physicianif PEF decreased by 20% or more fromthe prestudy mean.Statistical MethodsAll analyses were performed on theintent-to-treat population, defined asall patients who had received at leastone dose of blinded study drug. Base-line patient demographics and screen-ing pulmonary function were assessedby inferential analyses, and diseasecharacteristics were assessed by sum-mary statistics for each treatmentgroup. FEV1 values at individual timepoints and the average (weighted bytime intervals) of all postdose FEV1values on visits with 12-hour spirom-etry tests were summarized and com-pared between treatment groups usinganalysis of covariance (ANOVA), withbaseline as the covariate and adjusted

VOLUME 84, MARCH, 2000 335

for investigator’s effect. Treatmentcomparisons for onset and durationwere based on the van Elteren test, andpeak effect was based on ANOVA Ftests. Between-treatment differences inself-rated asthma symptom scores,nighttime awakenings, and supplemen-tal albuterol were determined by de-scriptive and inferential analyses. A Pvalue of .05 or less was consideredstatistically significant for all treatmentcomparisons.

RESULTSPatients and DemographicsA total of 498 patients (mean age 33years; range 12 to 79 years) with mild-to-moderate asthma (FEV1 � 50% to85% of predicted) were randomly as-signed into three treatment groups (sal-meterol powder, n � 165; salmeterolaerosol, n � 166; placebo, n � 167).Table 1 presents demographic, asthmahistory, and baseline spirometry datafor all patients. There were no statisti-cally significant differences in demo-graphic parameters, general asthmaand asthma symptom history, andbaseline FEV1 among the three treat-ment groups. Approximately half ofthe patients had a history of asthma for�15 years, and 79% did not require

acute care (treatment at a doctor’s of-fice, ambulatory care facility, or emer-gency room) for asthma exacerbationwithin the year preceding study entry.Approximately one-third of the pa-tients were taking inhaled corticoste-roids; a similar number of patients ineach treatment group were on an in-haled corticosteroid regimen at base-line. The mean pre-medication FEV1was approximately 68% of predicted inall treatment groups, with no signifi-cant differences between the treatmentgroups.Three hundred ninety-five (79%)

patients completed the study, including134 (81%) in the salmeterol powdergroup, 139 (84%) in the salmeterolaerosol group, and 122 (73%) in theplacebo group. One hundred and threepatients (20%) withdrew from thestudy prematurely due to failure to re-turn, protocol violation, lack of effi-cacy, or adverse events (Table 1). Al-though withdrawals due to adverseevents were slightly higher in the sal-meterol powder group (4.9%) com-pared with the salmeterol aerosolgroup (1.2%) and placebo (3.6%), theevents were primarily due to infections(bronchitis, upper respiratory infec-tion, influenza, mononucleosis, chole-

cystitis) or to other completely unre-lated events (ovarian cyst, syncope,allergic reaction to allergy shot).EfficacyIn both salmeterol treatment groups,FEV1 increased significantly within 30minutes of study drug administrationand peaked between 2 and 4 hourspostdosing at both day 1 and week 12of the study. Peak FEV1 increased by21% and 24% over baseline for theDiskus powder and the aerosol MDI,respectively, compared with a 9% in-crease in FEV1 for placebo on treat-ment day 1. Mean percent increases inFEV1 from baseline were significantlyhigher in the two salmeterol groupscompared with the placebo group at alltimepoints 30 minutes postdosingthrough 12 hours (P � .001; Fig 1).There were no significant differencesin the improvement in pulmonaryfunction between the two salmeterolformulations during the entire 12-hourpostdosing period. At week 12, meanFEV1 increased by 23% and 22% overbaseline for the Diskus and the MDI,respectively, compared with a 9% in-crease in FEV1 for placebo.The mean increases in FEV1 from

baseline were again significantly

Table 1. Demographic and Baseline Characteristics and Withdrawals

Characteristic Salmeterol powder Salmeterol aerosol Placebo Total

Number of patients 165 166 167 498Sex, n

Male/Female 79/86 78/88 78/89 235/263Ethnic origin, n (%)

Caucasian/White 131 (79) 135 (81) 128 (77) 394 (79)Black 18 (11) 12 (7) 19 (11) 49 (10)Hispanic 15 (9) 18 (11) 19 (11) 42 (8)Other 1 (�1) 1 (�1) 1 (�1) 3 (�1)

Age (yrs)Mean 33 35 34 34Range 12 to 74 12 to 79 13 to 74 12 to 79

Concomitant inhaled corticosteroids, n (%) 55 (33) 51 (31) 60 (36) 166 (33)Mean FEV1 (SE)

Screening (L) 2.40 (0.05) 2.38 (0.05) 2.37 (0-.04) —% of predicted 67.8 (0.81) 67.8 (0.81) 67.9 (0.76) —% Reversibility 29.1 (1.14) 28.2 (1.08) 27.9 (0.92) —

Withdrawals, n (%)Failed to return 8 (4.9) 3 (1.8) 15 (9.0) 26 (5.2)Protocol violation 8 (4.9) 12 (7.2) 9 (5.4) 29 (5.8)Lack of efficacy 7 (4.2) 10 (6.0) 15 (9.0) 32 (6.4)Adverse event 8 (4.9) 2 (1.2) 6 (3.6) 16 (3.2)


higher in the two salmeterol groupscompared with the placebo group at alltimepoints from 30 minutes postdosethrough 12 hours (P � .001; Fig 1).The treatment responses on treatmentday 1 and treatment week 12 weresimilar. Results seen at treatment week4 (not shown) were comparable tothose at treatment week 12. Similarresults to those above were obtained onanalysis of percent predicted values.Subgroup analyses revealed no impor-tant differences in the response totreatment based on gender, ethnic ori-gin, or for patients using inhaled cor-ticosteroids versus those not on inhaledcorticosteroids.

Baseline AM PEFs were not signifi-cantly different between treatmentgroups (mean PEFs of 390 � 102L/min, 392 � 90 L/min, and 389 � 90L/min in the salmeterol powder, sal-meterol aerosol, and placebo groups,respectively). After administration ofstudy drug, mean AM PEFs were sig-nificantly higher in the salmeterol-treated groups than in the placebogroup (salmeterol powder versus pla-cebo, P� .004; salmeterol aerosol ver-sus placebo, P � .003) throughout the12-week treatment period (Fig 2).Over the 12-week treatment period,mean increases in AM PEF ranged from17 to 31 L/min in the salmeterol pow-

der group, 22 to 30 L/min in the sal-meterol aerosol group, and 7 to 17L/min in the placebo group.Compared with the placebo group,

the salmeterol groups demonstratedsignificant decreases in daily supple-mental albuterol use, days without al-buterol, decreases in the number ofasthma-related nocturnal awakenings,and increases in the percentage of dayswith no asthma symptoms for the en-tire 12-week period (Table 2). Supple-mental albuterol use declined sharplyin the salmeterol-treated groups duringthe 12-week treatment period com-pared with placebo. No significant dif-ferences between salmeterol-treatedgroups were observed in these mea-sures of efficacy.SafetyAdverse Events. No clinically signifi-cant between-group differences wereobserved in hematology and clinicalchemistry laboratory tests, vital signs,ECGs, 24-hour ambulatory Holtermonitoring, physical examination re-sults, or adverse events. The incidenceof adverse events considered by theinvestigator to be possibly or probablyrelated to study drug was comparablebetween treatment groups. Eleven pa-tients (7%) in the salmeterol powder

Figure 1. Twelve-hour serial forced expiratory volume in 1 second (FEV1) for salmeterol powder(closed circles), salmeterol aerosol (open circles), and placebo (open squares) treatment groups ontreatment day 1 (A) and at treatment week 12 (B). Data are plotted as the mean � standard error.

Table 2. Summary of Albuterol Use, Nighttime Awakenings, and Asthma Symptoms

Parameter

Salmeterol Powder Salmeterol Aerosol Placebo

Mean(SE)

Change(SE)

Mean(SE)

Change(SE)

Mean(SE)

Change(SE)

Back-up albuterol use (number of puffs per day)Baseline 4.5 (0.4) 3.7 (0.2) 3.5 (0.2)Weeks 1–12 2.3 (0.2) �2.1 (0.4)* 1.8 (0.2) �1.9 (0.2)* 2.9 (0.2) �0.7 (0.2)

Days without albuterol, %Baseline 17 (2) 22 (3) 20 (3)Weeks 1–12 39 (3) 23 (3)* 52 (3) 29 (3)* 34 (3) 14 (3)

Nights without awakenings, %Baseline 66 (3) 67 (3) 67 (3)Weeks 1–12 78 (2) 12 (2)* 84 (2) 16 (2)* 71 (2) 4 (2)

Days without symptoms, %Baseline 25 (3) 28 (3) 27 (3)Weeks 1–12 44 (3) 19 (3)* 50 (3) 20 (3)* 37 (3) 10 (2)

Daily mean of asthma symptom scoresBaseline 2.2 (0.1) 2.2 (0.1) 2.2 (0.1)Weeks 1–12 1.9 (0.1) �0.4 (0.1)* 1.8 (0.1) �0.4 (0.1) 2.0 (0.1) �0.2 (0.1)

* Indicates significant difference (P � .05) from placebo treatment.† Indicates significant difference (P � .05) between salmeterol treatments.SE, standard error of the mean.


group, 9 patients (5%) in the salmet-erol aerosol group, and 6 patients (4%)in the placebo group experienced ad-verse events considered by the inves-tigators to be related to study medica-tion. The most common drug-relatedadverse event was headache, and theincidence of this event was low (2%)and similar in the three treatmentgroups. Overall, there were no statisti-cally significant between-group differ-ences in the incidence of drug-relatedadverse events.Vital Signs. Baseline heart rates were

similar between treatment groups ontreatment day 1 (72 to 73 beats/minute)and at treatment week 12 (71 to 73 beats/min). Changes in heart rate did not ex-ceed 2 beats/min, and were similar ontreatment day 1 and at week 12. Therewere no statistically significant between-treatment changes from baseline in serialheart rates following study drug at alltime periods evaluated.Arterial systolic/diastolic blood

pressures at baseline were similar be-tween treatment groups on treatmentday 1 (114 to 115 mmHg systolic and72 to 74 mmHg diastolic) and at treat-ment week 12 (113 to 115 mmHg sys-tolic and 73 mmHg diastolic). Therewere no significant changes in systolic/diastolic blood pressures in any treat-ment group during the 12-week treat-ment period.

ECG and Holter Monitoring. Noneof the patients in these studies hadECG results that were determined to beabnormal and clinically significant atscreening or at week 12. None of thepatients had clinically significant unfa-vorable ECG changes from baseline atthe week 12 postdose evaluation.Sixty-three patients had continuous

ambulatory electrocardiographic (Holter)monitoring for the 24 hours during thescreening period, 65 patients hadHolter monitoring for 12 hours at treat-ment day 1, and 41 patients had Holtermonitoring for 12 hours at treatmentweek 12. At screening, mean cardiacrates were significantly higher in theplacebo and salmeterol powder groups(83 and 81 beats/min) than in the sal-meterol MDI group (75 beats/min)(P � .005), and this significant differ-ence was maintained on treatment day1 (P � .013). No significant differ-ences were observed across the treat-ment groups at week 12, with heartrates ranging from 75 to 79 beats/min.Maximum and minimum cardiac rateswere similar on treatment day 1 andtreatment week 12 across all treatmentgroups.The median number of ventricular

ectopic beats (ie, premature ventricularcontractions) over 12 hours was com-parable and low, with 75% of patientsin each treatment group having �2

ventricular ectopic (VE) beats in 12hours at day 1 and week 12. The over-all number of patients with VE runs(three or more VE beats in a row)and/or �50 VE episodes in 12 hourswas low and similar on both study days(9% and 0% on day 1 and week 12,respectively, for placebo, 5% and 6%on day 1 and week 12 for salmeterolpowder, and 5% and 6% on day 1 andweek 12 for salmeterol MDI).Supraventricular ectopic events

(SVEs) also occurred at low rates in alltreatment groups. The rates of morethan 50 SVEs in the 12-hour periodwere low and similar in all treatmentgroups (0% at both day 1 and week 12for placebo, 5% and 0% at day 1 andweek 12, respectively, for salmeterolpowder, and 0% at both timepoints forsalmeterol MDI).

DISCUSSIONThe results of this study demonstratethe comparability of salmeterol pow-der and salmeterol aerosol formula-tions in the treatment of patients withasthma. Both salmeterol formulationselicited sustained bronchodilation forup to 12 hours over the 12-week treat-ment period. The efficacy of treatment,as reflected by the percent change frombaseline of FEV1 values, did not sig-nificantly differ in subgroups based ongender, ethnic origin, or users or non-users of concurrent inhaled steroids.Both salmeterol powder and salmeterolaerosol were effective in improvingasthma symptoms, reducing supple-mental albuterol use and nighttimeawakenings, and increasing the per-centage of days without symptoms.These data demonstrate that the effi-cacy and safety of the powder formu-lation of salmeterol is comparable tothat of salmeterol aerosol and that bothsalmeterol formulations are signifi-cantly more effective than placebo.The results of the present study are

consistent with previous studies em-ploying salmeterol powder via theDiskhaler21–26 and salmeterol aerosolvia the MDI.2,3,27,28 The results fromthose studies demonstrated that salme-terol aerosol administered by MDIand salmeterol powder by Diskus or

Figure 2. Summary of the weekly mean morning peak expiratory flow (PEF) in salmeterol powder(closed circles), salmeterol aerosol (open circles), and placebo (open squares) treatment groups. Baselinecomprised the average of the 7 days immediately before treatment day 1. Data are plotted as the mean �standard error. *Indicates significant difference between salmeterol powder and placebo. †Indicatessignificant difference between salmeterol aerosol and placebo.


Diskhaler provides effective bron-chodilation for up to 12 hours and isefficacious and safe for long-term reg-ular use.3,4,7,29–31Salmeterol therapy was well toler-

ated for the duration of the trial. Ad-verse events considered drug-relatedwere minor and of little clinical con-cern. Vital signs and ECG results weresimilar among the treatment groups.Holter monitoring results were similaracross the treatment groups at day 1and week 12.In the present study, there was no

evidence that the bronchodilator prop-erties of salmeterol became attenuatedover the 12-week treatment period.The finding of no significant diminu-tion in bronchodilation with salmeterolin the present study is consistent withthe findings of 1 year studies by Brit-ton et al4 in adults and Simons et al inchildren,32 and in other 3-month stud-ies in adults.2,3 Tolerance to the effectsof beta-agonists in vitro has been dem-onstrated; however, this effect leadingto down-regulation of beta adrenergicreceptors in some tissues and de-creased pharmacologic response invitro does not translate to diminishedclinical control of asthma for patientswho do not exceed recommended dos-ages of beta adrenergic agonists overprolonged periods of time.33In conclusion, results from this

study demonstrate that salmeterolpowder 50 �g BID via the Diskus is asefficacious as salmeterol aerosol 42 �gBID via MDI. Salmeterol via the Dis-kus produces clinically significant im-provement in pulmonary function inadolescent and adult patients withmild-to-moderate asthma comparableto that seen with the MDI formulation.The Diskus offers a simple and easy-to-use alternative for patients who ex-perience difficulties with the use of apressurized MDI.

ACKNOWLEDGMENTSThe authors gratefully acknowledgecontributions from the following in-vestigators and their patients: WilfredBeaucher, MD; William Berger, MD;Arthur DeGraff, MD; Robert Dock-horn, MD; David Elkayam, MD; Tra-

vis Ellison, MD; Mark Goldstein, MD;Richard Gower, MD; Frank Hampel,Jr, MD; Gary Incaudo, MD; WilliamLumry, MD; Jonathan Matz, MD; JohnMcGee, MD; Mark Menzel, MD; An-juli Nayak, MD; Robert Noveck, MD,PhD; Bruce Prenner, MD; SantiagoReyes, MD; Eric Schenkel, MD; JohnSelner, MD; William Stricker, MD;Robert Webb, MD; John Van Wye,MD. We would also like to thankLarry E. East for his expert assistancein writing and editing this manuscript.

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James Wolfe, MDAllergy and Asthma Associates of Santa ClaraValley

4155 Moorpark AveSan Jose, CA 95117


comparison of powder and aerosol formulations of salmeterol in the treatment of asthma

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