thorax compliance with inhaled asthmamedication in

Thorax 1995;50:1274-1279

Compliance with inhaled asthma medication inpreschool children

Neil A Gibson, Allison E Ferguson, Thomas C Aitchison, James Y Paton

AbstractBackground - Previous studies haveshown poor compliance with regular drugtherapy in children and adults withasthma. In preschool children the parentssupervise and are responsible for drug ad-ministration, but little is known of com-pliance in this group. In addition, thereare few data on the patterns of drug useofinhaled prophylactic asthma therapy orof the relation between compliance andsymptom control. A study was undertakento address these issues with the hypothesisthat parental supervision would result ingood compliance.Methods - The subjects were 29 asthmaticchildren aged 15 months to five years al-ready established on inhaled prophylacticmedication delivered through a large vol-ume spacer. The prescribed drug regimensvaried between subjects. This was an ob-servational study using an electronic in-haler timer device to record the date andtime of each actuation of the aerosol can-ister. Diary cards were used for parallelrecording of symptoms and parentally re-ported compliance with a drug regimen.Results - Variable and generally poor com-pliance was demonstrated with a medianof 50% of study days with full compliance(subject range 0-94%) and an overall me-dian of 77% ofprescribed doses oftherapytaken during the study period. No relationwas foundbetween frequency ofprescribedregimen and good compliance. Day carewas associated with poorer compliance.No relation between good compliance andlow symptom scores was found.Conclusion - Compliance with inhaledprophylactic therapy is poor in preschoolchildren with asthma whose medication isadministered under parental supervision.(Thorax 1995;50:1274-1279)

Keywords: young children, asthma, drug compliance.

The prevalence of asthma is increasing world-wide, especially in young children. The generalresponse to inhaled therapy in preschool chil-dren with asthma is variable. This may stempartly from the heterogeneity of the disease inyoung children, and partly from difficultiesassociated with inhaled drug delivery at thisage.' Another potentially important factoraffecting treatment success or failure which hasnot been addressed to date in this age group isthe degree of compliance with inhaled drugtherapy. We have previously shown that patient

compliance with inhaled prophylactic therapyin schoolchildren with asthma is poor, espe-cially when the prescribed dose is more thantwice a day.2 However, we know of no studiesof parental compliance and its effect on drugadministration to their children.

Inhaled medication via a large volume spaceris increasingly being used in young childrenwith asthma. In this study we have investigatedthe use ofprophylactic medication in a group ofpreschool children using an electronic inhalertimer device. Such a group differs from olderchildren in that their asthma therapy is ad-ministered either directly or under the closesupervision of their parents. Supervision is atechnique that has been used to improve com-pliance in other areas.3 In this study we hy-pothesised that parental involvement throughsupervision ofdrug administration would resultin better compliance than that seen in otherasthma patient groups.

MethodsSUBJECTSA group of preschool children attending a spe-cialised paediatric respiratory clinic were re-cruited. The entry criteria were that the childwas receiving regular prophylactic asthma med-ication by metered dose inhaler through largevolume spacer devices (cromoglycate, bude-sonide via Nebuhaler, or beclomethasone viaVolumatic) and had been using such med-ication for at least a month before entry to thestudy. The study was observational in designand no changes were made in the children'streatment.

Parents were invited to participate and re-ceived written and verbal explanation of thestudy and its aims. The technique of ad-ministration by the tidal breathing method4via the large volume spacer was checked andcorrected if necessary. A study period of twomonths was planned. A troubleshooting tele-phone call was made after two weeks to checkif there were any problems with the devices.All subjects were given an appointment at theend of the study period. There was open accessby telephone for any problems encountered bythe subjects.

ELECTRONIC TIMER DEVICETo measure inhaler use we used the NebulizerChronolog NC300 (Forefront TechnologiesInc, Lakewood, Colorado, USA) (fig 1). Thisis an electromechanical timer device whichtakes the place of the plastic holder of themetered dose inhaler. It incorporates a micro-

Department of ChildHealth,Royal Hospital forSick Children,Glasgow G3 8SJ, UKN A GibsonA E FergusonJ Y Paton

Departnent ofStatistics,University of Glasgow,Glasgow G12, UKT C Aitchison

Reprint requests to:Dr N A Gibson.This paper was presented inpart at The AmericanThoracic Society Meeting inSan Francisco, May 1993and the relevant abstract waspublished in Am Rev RespirDis 1993;147:A576.

Received 21 April 1995Retumed to authors11 July 1995Revised version received21 August 1995Accepted for publication29 August 1995

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Compliance with inhaled asthma medication in preschool children

Figure 1 A Chronolog device loaded with an aerosol, attached to a Nebuhaler.

switch which is activated on each firing of theaerosol and allows the accurate recording ofthe date and time of each actuation of themetered dose inhaler. The Chronolog is ini-tialised using dedicated computer softwarethrough a Medilog adapter attached to an IBMPC computer. It is then loaded with themetered dose inhaler canister and is ready foruse with the large volume spacer. The batterylife is over six months and the device can

electronically store up to 4000 events. In a

validation study we found it to be accurate towithin 10 minutes over the course ofone monthof study (unpublished data). Hence, the devicewas capable of providing detailed informationon the pattern of use of the metered doseinhaler over the course of the study.A separate Chronolog was issued for each

subject's inhaled "prophylactic" medication(inhaled steroids or cromoglycate) and for theirbronchodilator (terbutaline or salbutamol).The result of study of the use of the bron-chodilator medication is the subject of a sep-arate paper5 and is not further discussed. Theprescribed drug, its dose and frequency were

detailed on a sticker attached to the back ofeach device (for example, cromoglycate twopuffs four times a day).When the device was returned at the end of

the study period the Chronolog data were readby the program and a printout of all times anddates of use of the metered dose inhaler over

the study period was prepared. The resultswere discussed with the parents and children.This allowed the opportunity to record com-ments and discuss any difficulties encountered.

INFORMATION GIVEN TO SUBJECTSThe prescribed medication regimen for eachchild was written on a standard asthma card(National Asthma Campaign, London, UK)which also gives advice on patient self-man-agement. The regimen was also detailed on thesymptom diary card, in addition to the labelon the back of each Chronolog. Each subjectalso had written material that explained the

nature and accuracy of the timing device andthe rationale of the study.A symptom diary card was issued on which

parents were asked to record daytime cough,night cough, and wheeze using a four pointscale for each symptom, and also to record theuse ofthe inhalers. Parents were asked to recordon the symptom diary card any instances wherethey used asthma medication other than thestudy aerosol in the Chronolog and to noteany firing of the aerosol when drug was notadministered - for example, in play by thechild. Subjects were not instructed to increaseinhaled prophylactic therapy in the presence ofincreased symptoms.

ETHICSThe study was approved by the ethics com-mittee of the Royal Hospital for Sick Childrenand informed written consent was obtainedfrom all parents. As noted, it was made veryclear in the written and verbal instructions thatthe device would record the date and time ofeach use of the metered dose inhaler.

MEASURES OF COMPLIANCEIn the initial instructions parents of subjectswere asked to shake the canisters before usebut not to "test fire" the metered dose inhaler.We therefore assumed that each recorded actu-ation represented administration of the med-ication. The data were assessed manually andeach day scored for two measures of com-pliance. The first, "Daycomp", was the pro-portion of the total study days on which theprescribed number of puffs was recorded at theprescribed frequency. The spacing ofactuationshad to be consistent with the schedule of apreschool child - for example, two puffs at08.00, 12.00, and 19.00 hours for a three timesdaily regimen. We accepted a gap of two hoursbetween actuation times as the minimum ac-ceptable spacing. Daycomp was therefore ameasure of the number of days of strict ad-herence to the prescribed regimen. The secondmeasure, "Dosecomp", was the proportion ofactually administered to total prescribed dosesover the entire study period. We ignored any"extra" puffs on the very rare study days onwhich more than the prescribed number ofpuffs was recorded. Dosecomp therefore gavean overall indication of use of the inhaled med-ication and provided a less demanding measureof compliance. A note was also taken of thenumber and pattern of days on which theChronolog recorded no use of prophylacticmedication.A total symptom score for each day was

calculated from the diary cards. The diarieswere also used to score the parents' writtenrecord ofcompliance to the prescribed regimen,"Reported Compliance".

STATISTICAL ANALYSISAs the number of fully compliant days is aninteger and clearly dependent on the actualnumber of days studied separately for each

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individual, cognisance of this must be em-

ployed in any analysis. This is achieved hereby using a "logit" (or logistic) approach whichmodels the ratio of the number of compliantto non-compliant days.The effects of possible factors influencing

compliance, such as frequency of prescription,daycare, etc were analysed by means of gen-

eralised linear models taking the logarithm ofthe odds ratio of the compliance measure as a

response variable. Individuals were modelledby means of random effects with estimatedvariances determined by the above "logit"transformation. For example, to compare thedaily compliance rates on average across thethree frequencies of prescription (two, three,or four times daily) a weighted one way analysisof variance was carried out on the logarithmsof the number of actual fully compliant daysdivided by the number of days on which thesubject did not comply.

ResultsOver a 13 month period the parents of 36children were approached to seek participation.In seven children the parents declined to par-

ticipate, most frequently after expressing con-

cern at the commitment of time necessary forproper conduct of the study. Twenty nine chil-dren aged 15 months to five years were there-fore recruited. Details of the children are

included in the table. Most found the timerdevice to be acceptable, but some difficultieswere experienced. One subject did not returnthe Chronolog devices or diary cards. Twosubjects were withdrawn from the study afterdifficulties with the fit of the cromoglycateaerosol into the Chronolog which resulted inthe electronic switch "sticking" with the docu-mentation of large numbers of actuations anddifficulty in using the metered dose inhaler.One further subject had poor symptom controland was changed from cromoglycate to inhaledsteroids 18 days into the study. The data for

that subject were only analysed for the first 18day period. Satisfactory Chronolog data were

therefore available for 26 subjects. The mediannumber of days studied was 58 days (range15-94). Three subjects did not keep or did notreturn diary cards.

Compliance with inhaled prophylactic ther-apy was variable and often very poor as shownin the values for Daycomp and Dosecomp inthe table. We were interested to note that therewas no relation between either good Daycompor good Dosecomp and low symptom scores.

Inspection of the data printouts showed thatonly 11 of the 26 subjects took at least some

prophylactic therapy on each study day. Tenchildren had consecutive days when they were

given no treatment; five children had no med-ication use recorded for seven or more con-

secutive days despite the fact that the parentsreported their child to have symptoms on a

mean of 63% of study days. Many parentscontinued to record symptoms during periodswhen they were not apparently administeringthe prophylactic treatment. The symptom diarycard data also showed that most parents re-

ported compliance to be better than that ac-

tually measured (table).Undercompliance, when it occurred, usually

consisted of missing a time of administrationrather than omitting doses at actuation times.From examination of the printouts it was clearthat in those with a three or four times/dayregimen it was generally the doses in the middleof the day that were omitted. Examples ofthe patterns of compliance to the prescribedregimens are shown in fig 2. It can be seen thatmost show variation in compliance, but thisvariation did not correlate with fluctuations insymptoms. When the first 20 days of the studywere compared with the next 20 days there wasa significant drop of 7% in both Daycomp(p<005) and Dosecomp (p<0 05). This sug-

gests that there may have been a study effectresulting in improved compliance at the be-ginning of the study.

Characteristics of children included in the study

Patient Age Day Drug Frequency Study days with Reported Daycomp Dosecompno. (years) care (per day) symptoms (%o) compliance (%o) (%) (%)

1 4-8 N Cromoglycate 4 58 98 91 992 3 6 Y Cromoglycate 4 95 89 87 973 2-8 N Cromoglycate 4 73 77 61 884 2-9 N Cromoglycate 4 4 92 36 775 4-7 Y Cromoglycate 4 100 11 0 396 1-3 N Cromoglycate 4 74 13 40 777 2-0 Y Cromoglycate 4 100 18 3 178 2-1 N Cromoglycate 4 100 50 48 599 4-1 Y Budesonide 3 65 40 45 5510 5 0 N Cromoglycate 3 39 73 41 7511 3 0 Y Budesonide 3 38 92 65 9012 2-2 Y Cromoglycate 3 29 25 26 6813 3-7 Y Budesonide 3 100 99 67 8914 3-8 Y Cromoglycate 3 No data No data 50 7115 4-8 N Budesonide 2 58 100 51 7316 3-4 N Budesonide 2 85 90 82 9117 4-6 Y Budesonide 2 41 85 82 9018 4-8 Y Budesonide 2 100 81 23 4819 3-8 Y Budesonide 2 100 95 4 1520 4 8 N Budesonide 2 45 88 84 8921 4 9 N Beclomethasone 2 27 No data 94 97

dipropionate22 3-3 Y Beclomethasone 2 45 100 12 22

dipropionate23 3-8 Y Budesonide 2 No data No data 82 9124 3 2 Y Budesonide 2 94 67 33 5425 2-3 N Budesonide 2 100 100 82 9426 1-5 N Budesonide 2 No data No data 88 93

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Compliance with inhaled asthma medication in preschool children

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Figure 2 Each graph represents the pattern of use of inhaled prophylactic medication over the first 31 days of the study ina single subject. The vertical axis is the number of puffs taken on a particular day. Each study day is represented as a bar.The horizontal line represents the number of puffs that denotes full compliance with the prescribed regimen.

Day care was used for 17 of the children butwas full time in only two, both of whom hadpoor Daycomp (23% on a twice daily regimenand 26% on a three times daily regimen). Therewas a significant adverse effect on Dosecompof those in day care (p<005) but not for Day-comp. This finding was interesting as enquiryat study entry had revealed that no child was

normally given their prophylactic drug at daycare. The poorer compliance in children in daycare is not therefore due to the omission ofdoses by carers in day care, but rather to pooreroverall parental compliance in children whoattended day care.

In this group of children we found no sig-nificant difference in compliance between re-

gimens of two, three, or four times daily, witheach group showing marked variation in Day-comp and Dosecomp as demonstrated in fig 3.When the discrepancy between reported

compliance and recorded compliance was re-

vealed at the end of the study parents were

often keen to offer explanations of happeningswithin the family that had had an adverse effecton compliance. They were often at pains toexplain these as unusual - for example, deathsof elderly relatives, hospitalisation of relatives,holidays.

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DiscussionIn this study we found clear evidence ofvariableand often poor compliance with inhaled pro-

phylactic medication in preschool children with

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Figure 3 Scatter of values for (A) Dosecomp and (B)Daycomp. Each subject is plotted once on each graph.BD=twice daily; TDS=three times daily; QDS=fourtimes daily.

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Gibson, Ferguson, Aitchison, Paton

asthma. This occurred despite the fact that thesubjects of the study were having medicationadministration supervised by their parents. Themeasured compliance was little better than ina previous study in school age children2 or inadult studies of aerosol use.67

It has been reported that participation in atrial or study8 may lead to improved compliancewith treatment. This was particularly likely inthis study as the Chronolog's ability to timeand date each actuation was carefully explainedto the parents at enrolment to the study. In-deed, our data provide some evidence for aneffect of study participation on compliance aswe have shown a significant deterioration incompliance with the prescribed regimen overtime. This suggests that our results may, infact, be an overestimation of true medicationcompliance in the preschool asthmatic popu-lation. However, Rand and colleagues7 showedthat the use of a Chronolog per se did notappear substantially to improve complianceduring a long term study, but that if feedbackwas given the compliance improved.9 We didnot restudy these subjects after the feedbackwas given at the end of the study.One potential confounding factor could be

the actuation of the inhaler without the dosebeing inhaled such as in "test firing". This wasactively discouraged at enrolment to the study.In any event, test firing, if it occurred, wouldlead to apparently better compliance. In thisrespect we noted that most undercompliancewas due to omission of times of administrationand that taking too many puffs per ad-ministration was not a phenomenon observedin this study population. Another finding notedin children2 and well demonstrated in adults7is that of "canister dumping" - that is, largenumbers of actuations occurring in a very shorttime period thought to be due to repetitiveactuations without inhalation. This unexpectedbehaviour has been thought to be due to apatient attempting to get up to the "correct"number of actuations during the study periodby "catching up" for previously omitted doses.As noted, we took care to make our subjectsaware of the abilities of the Chronolog and wedid not see this phenomenon with prophylactictherapy in the present study. We did see somesubjects for whom doses of prophylactic med-ication were noted very late in the evening orin the early hours of the morning, well after apreschool child's likely bedtime. These weregenerally explained by the parents as ad-ministration to a sleeping child.A trend towards better compliance with less

frequent administration times was noted in aprevious study in older children2 and has beenseen in other conditions in different agegroups.'01' In a study of school aged asthmaticchildren Williams et all2 attributed the bettercompliance with a twice daily regimen to theavailability of parental supervision of inhaleruse in the morning and evening. Our datasuggest that in preschool children the in-volvement ofparents does not significantly alterinhaled medication use. Furthermore, from ourdata there was no clear trend towards bettercompliance when fewer daily administration

times were prescribed. The striking finding isthat, within each group of two, three, or fourtimes a day administration there is a widevariation in the use of inhaled prophylacticmedication.One feature of concern was the number of

days that patients received no prophylactictherapy at all, on occasion for several days ata time (fig 2). While it is possible that anothermetered dose inhaler was used during theseperiods, parents were asked to record and re-port such occurrence. We also noted that ingeneral there was no clear relation betweenhigh scores for compliance and low scores forsymptoms. This may be an important factor inexplaining the poor compliance as perceivedeffectiveness is said to be a promoter of drugcompliance.'3 In these preschool asthmaticpatients positive feedback from good symptomcontrol was not present to reinforce good com-pliance with the prophylactic drug regimen.Adult data have also shown a similar lack ofcorrelation between symptoms and complianceto a regimen of four times a day inhaled ster-oid. 4Why do parents adhere poorly to prescribed

treatment regimens for their preschool asth-matic children? An important feature may wellbe that those responsible for drug ad-ministration are not those who experience thesymptoms first hand. Nevertheless, it was theparents who both scored their child's symptomsand gave the treatment. We took great care toemphasise by written and verbal instructionsthe prescribed medication and its mechanismof action. Despite this, misunderstanding ofthe rationale of regular prophylactic therapystill persists. It is also likely that some parentsremain unconvinced of the benefits or are fear-ful of the side effects of regular medication.'5The home of an average toddler is a busyenvironment and a degree of disorganisationmay be implicit and contribute to the poorobserved compliance. However, against this ithas to be noted that the number of siblings wasnot significantly associated with either Dose-comp or Daycomp.These findings potentially have an important

bearing on the planning of therapy in preschoolasthmatic children. For example, once dailyanti-inflammatory medication in these childrenwould probably not have been appropriate as58% of subjects had days on which no treat-ment was taken at all. Interestingly, adultdata'0" suggest that compliance with a oncedaily medication is little better than with twicedaily, and the pharmacotherapeutic importanceof a missed day of once daily medication maybe greater. Hopefully, measurement of actualinhaler use may lead to the prescription ofmoreempirically based medication to young childrenin the future.We conclude that compliance with inhaled

prophylactic therapy in preschool asthmaticchildren is poor. We speculate that poor com-pliance is likely to be an important factor inthe difficulty experienced in achieving controlof symptoms in such children. In future wethink it will be important to address specificallythe issue of drug compliance and factors which

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Compliance with inhaled asthmia nmedication in preschool children

affect it in studies of prophylactic inhaled med-ication in young children.

The Chronolog devices were purchased with financial assistancefrom Glaxo and the University of Glasgow.

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7 Rand CS, Wise RA, Nides M, Simmons MS, Bleecker ER,Kusek JW, et al. Metered-dose inhaler adherence in aclinical trial. Anii Rev Respir Dis 1992;146:1559-64.

8 Reiser J, Warner JO. Value of participating in an asthmatrial. Lanicet 1985;i:206-7.

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11 CramerJA, Mattson RH, Prevey ML, Scheyer RD, OuelletteVL. How often is medication taken as prescribed? A novelassessment technique. JAMA 1989;261:3273-7.

12 Williams H, Verrier Jones ER, Sibert JR. Twice daily versusfour times daily treatment with beclomethasone di-propionate in the control of mild childhood asthma. Thor-ax1986,41:602-5.

13 Eraker SA, Kirscht JP, Becker MH. Understanding andimproving patient compliance. Ainn Initenm Med 1984;100:258-68.

14 Mann MC, Eliasson 0, Patel K, ZuWallack RL. An evalu-ation of severity-modulated compliance with q.i.d. dosingof inhaled beclomethasone. Chest 1992;102:1342-6.

15 Radius SM, Becker MH, Rosenstock IM, Drachman RH,Schuberth KC, Teets KC. Factors influencing mother'scompliance with a medication regimen for asthmatic chil-dren.

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