Randomized comparison of two spacer devices in subjects with reversible airflow limitation

OBJECTIVE: To assess a new spacer device. the ACE. by comparing 
it with the Aerochamber in subjects with reversible airflow 
limilation and assessing the change in lung function after inhaled bronchodilator.

In ad<lilion lo improving <lclivcry of the <lrug Lo the lung.spacer <ll:'viccs re<lLILT oropharyngeal <leposition of the inhaled medication , even in subjects who use the MDI in an optimal manner ( I 0-12).Nol only does this play a part in <lecrL•asing oropharyngeal adverse effects but it is particularly important now that it is rccogni1.e<lthat inhalc<l stcroi<ls have the potential to pro<lucc systcmiL• side etlcds ( 13-15).In or<lL'r Lo minimilL' Lhi.s potential for unwantc<l effects it is stan<lard practice to recommcn<l that all patients taking high dose inhaled corticosteroids use a spacer <levice.
Most patie.ntshavc to pay for their own spacer <lcviLT and for many this cost is prohibitive .We have e valuated a new spacer.the ACE ( Diemol<ling Healthcare Division.New York) which is approximately h,df the price of other spacers.We use<l a randomi1cd.single-blind.cross-over des ig n to rnmparc the ACE with the AenK•hamber (Trude ll Medical) anJ asscsse<l the change in lung function achicve<l after inhaled bronchodilator a.s the outcome measure.

METHODS
Thirty subjects with reversible airflow limitation were stuJicd.All had shown at least 15r1,, improvement in mean forced expirL'U volume in I s (FEY 1) in till' three months beforc the stu<ly.Al I subjL'L'ls were on inhale<l corticostcroi<ls and ha<l been stable for at least one month before the study.Subjects were stu<linl on two separate <lays in one week an<l at the same time of day.
On ead1 study <lay the subject withhcl<l all inhaled broncho-<li lators for at least 6 h.Baseline llow:volume curve was obtained tSensormedics PFT Horiwn Syste m 5).The best  Two pulls of inhalc<l bronchodilator (sal butamol) wcrc then delivered using one of the spacer devices and 15 mins later measure ments of flow an<l heart rate were repeated.
After a third puff and a 15 min wait , and thcn a rounh pull an<l another 15 min wail, measurements wac again made.On thc sccon<l day the other spacer device was used.The order of use of spacer <le vice was ran<lomized.
The inhalation tcchniquc with each spacer device was the same.Subjects were blin<lfol<le<l and li1L' technologist delivered the inhaled me<lication.The spacer dcvicc was placed in the subject's mouth and the subject was aske<l to seal the lips tightly.When the subjcct, breathing quietly.was al en<l expiratory lung volume the lL•chnologist actuated the MDI and then asked the subject to in.spire slowly to maximum inflation, and hol<l their brcath for IO s.A sernnd pull was a<lmin istered 30 s lalL•r in the same manner.Third an<l fourth puffs were delivere<l individually.
The inspiratory flow ralc was cnntrollc<l only hy the whi.stling apparatus at the distal cn<l or both <lcviccs.All thc subjects ha<l usL'U the AnochambLT before the study and were familiar with the re4uircmcnt to kt'ep inspiratory Clow r,ites low L'nough so as not to acti vale the whistle.
All subjects gave inforn1cd consent and tlJL• stu<ly was ap prove<l by the Hospital Research Advisory Committee.
Data from subjects were discarded if till' baseline FEY I on the two study days <liffercd by more than I 0%.Student paire<l t test was use<l to analyze differences in FEY 1. Y50, V25 and heart rate after two, three and four pulls of inhaled bronc hod i lator.

RESULTS
Eighteen men an<l 12 wumcn ( mean I± S D J age 63± I 6, range 20 to 79 years) were stu<lie<l.The mean FEY I at baseline was 1.38±0.66L (range 0.8 to J .. 1 ).Data from four subjects had to be <liscar<lcd becauSL' there was greater than 10% difference in baseline FEV I on the two stu<ly days.In all subjects on bolh study days thcrL' was a signilicanl increase in FEY 1 (Pdl.00I) after inhaled hronchodi lat or.There was no difference in the increase in FEY I on the two study days (P>0.25,Table L Figure I).The re was also no difference in the change in VSO or V25 after inhalcJ bronchodilator with either spacer device (P>0.25,'fable 1, Figure 2).

DISCUSSION
This sluJy has shown thal in palienls wilh reversihle airflow limitalion inhaled bronchodilator Jelivered wilh a new spacer device , lhe ACE, rcsulls in increases in !low ralL'S thal arc equivalent to lhose achieved when using the Aerocham ber, probahly lhe slandard spacer device in gene ral use in Canada.Wilh cilher spacer device .even alkr four puffs of inhall'd hronchodilator.there was no increase in hca11 ralc .This indicalcs lhal lhc ACE delivers aclequale amounts of drug to lhe lung wilhoul a lcnclency lo increase adverse effecls.
We chose to compare lhe AC E wilh the Acroc hamber in pa11 hccausc the Acrochambcr is lhe mosl commonly used device, b~1t also hccause lhe si1.c of lhc spacers is similar.The volume of lhe ACE is 170 ml while thal of the Acrochambc r is 145 ml.There is no clinical advanlage lo using largc' .r spacers ( 17,18).
The ACE and the Acrocharnbcr arc structurally different and ycl share .,omc similarities.They hoth have one-way inspiratory valves al lhc proximal end and whistling adaplors al lhe dislal end.The ACE, however, has an entrainmcnl hole

Puffs of Bronchodilator
Figure 2) 1Waxi11111111 e.1fiimtory.flm1• at 50% proximal tl> the valve.We did not finJ lhat lhis enlrainmcnt hole affected the hronchodilalion thal was achieved even al very low inspiralory !low rales in s-1111c of our subjects whose FEY I was less than I L.
Wilh lhc ACE lhe M DI canister ilself is placed in lhc adaplive opening at the proximal end of the Jcvice in frnnl of the inspiralory valve.Wilh lhe Acrochambcr nol onl y the canister hul lhc whole of ll1L' MDI is inserted into lhe rubher cap at the dislal encl of lhe device.The Aerochamhcr is therefore availahlc for use with all MDis whereas the ACE will only be applicable for canislcrs thal fit the aJaptive open mg.
This stuJy was single-blind with an eye mask prcvcnling the suhjccl from knowing which spacer device was used: lhc drug was delivered by lhc leehnologisl.We used lhis 111c1hod hccause we were testing the spacer device, not lhc abilily of lhe suhject to use an MDI and spacer.
As lhe study could not he double-blind we were concernc.dabout lhe possihilily of technologisl hias in Jclermining which uf lhe three flow volume curves oblaincJ should he used for measuremcnls.Bias was avoided hy using American Thoracic Society sl:mdards lo choose lhe best now volume curve from which flow measurements were ohlained ( I <1).
We used changes in airway calibre assessed by FEY I and V50 as lhe oulcome measure because lhcy reflccl lhc polential clinical and symplomalic benefit ln the palicnl will!airflow limilalion.
Although changes in lung function were similar whichever spacer device was used we cannol say thal drug delivery lo lhc lung was necessarily lhe same wilh bolh.However, ralhcr lhan assl'ss pulmonary deposition in this stuJy, we chose to use lhc clinically relevant outcome measures of lung function changes.
The study sample size is larger lhan has hcen used in mosl previous assessments of spacer devices, b11l the possihility of a typL: II error L'Xists.How eve r, the differences in bronchodilation between the two spacer devices was negligibll' and even if a type II stat istical error were to exist, it is unlikely to be clinically rekvant.
Spacer devicL'S are now commonly recommended when an MDI is prescribed to improve drug delivery to the lun g, reduce oropharyngeal side effects, and minimize the tot.JI dosL' of drug delivered -.111 important factor when high dose inhaled corticosteroids arc used.They arc parti cu larl y use !"ttl in the l'lderly anJ in childrrn.