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ORIGINAL ARTICLE
Overreliance on bronchodilators as a risk factor for life-threatening
asthma
PIERRE ERNST MD, B RENDA H EMMELGARN MN, DONALD W COCKCROFT MD, SAMY SUISSA PhD
Department of Epidemiology and Biostatistics and Department of Medicine, Montreal General Hospital, McGill University, Montreal; and Department of Medicine.
University of Saskatchewan, Saskatoon, Saskatchewan
P ERNST, 8 HEMMELGARN, OW COCKCROFT, S SUISSA. Overreliance on bronchodilators as a risk factor for life-threatening asthma. Can Respir .J 1995;2(1):34-39.
OH.JECTIVE: To assess the potential impact on the ri sk or life-threatening asthma of current recommendations in pharmacotherapy. which emphasize the early use of steroids and the avoidance of hL·ta-agonist overuse. DESIGN : Nested case-control study. SETIING: Province of Sasb.atchewan. POPULATION STUDrED: From a coho11 of 12,30 I subjects dispensed IO or more asthma medications from 1980 to 1987. 129 case patients were identified who had experienced an episode o[ fatal or near fatal asthma and 129 contro l patients matched to the cases on age. time period at risk and severity of asthma (as judged by the need for hospi ta lization for asthma in the preceding two years). METHODS: Two clinicians rev iewed the therapy these 258 subjects had been dispensed over the prior two-year period and classified their treatment as 'incompatible ' or 'compatihle· (at least partiall y compatible) with current pharmaco-
therapeut ic gui de li nes. In addition to this classification a treatment eva luation score was also applied to each study subject. T hi s score was based on the use of anti-intlammatory therapy (oral and inhaled) in conjunction with the regular use of bronchodi lators, as we ll as the use of oral corticosteroids for patien ts recently discharged fro m hosp ita l foll owing an attac k or asthma. RESULTS : At least one o f the two c lin ician reviewers judged the rapy to be incompati ble wit h current standards in 49~ o f the case pati e nts compared w ith 2W/r of" 1I1c subjec ts who had not experie nced a life-threatl'.ning episode. The mean ± SD treatmen t score was 3.5± 1.7 in cases compared wi th 0.8±1.4 in controls, suggesting quali ty or pharmacological treatment was worse in cases (P<0.00 I ). CONCLUSIONS : Pharmacolog ical therapy incompatible with current recommendations was more common among cases of fatal and near fata l asthma in Saskatchewan from 1980 tO l 98 7. ( f'OI / r reS /111//, I •o ir /l{[gC 35 )
Key Words: A,frcrse ef/ccts. Bc1a-ugn11ists. < ·,irricn1/cmid,. /)rug rherapr, /'vforhidit.1·. Mortulirr
Corropo11dc11ce: Dr Pierre !-.m ., 1, Re.1pimtvry Et>idemiolog_1• U11 i1. Depart111e111 of Epide111iology and Biostatistin . McGill U11ivcn it_1". ///() !'inc A1·e11m· West. Mo111real. Q11ehec 1/3, ·\ /,U. frlep/rone (5 /-/.J 398-6974. Fax (514) 398-8981
34 Can Respir J Vol 2 No 1 Spring 1995
La confiance excessive dans les bronchodilatateurs comme facteur de risque pour un episode d'asthme mettant la vie du patient en danger
OBJECTIF : Evaluer !'impact potentiel des rccornm::mdations en vigueur en maticrc de ph:1rmacotherapie. qui rappellent t.l'utiliser pn:cocement des stero'ides ct d\;vitcr la suruti lisation des bcta-agonistes. sur le risque d ' un cpismlc d'aslhme mcllanl la vie du patient en danger. Moo1tLE : EtuJc cas/lcmoins embo'itcs Co TEXTE : Province de la Saskatchewan. POPULATIO ETUDIEE : o ·une cohorte Jc 12 30 I sujets ;1 qui 011 a prcscril IO mcdicament.s :1nti-a.,thrnatiqucs cl plus. Jc 1980 ii 1987. 129 patients-cas lllll etc identilics qui avaicnt subi un L;pisodc lL1sth111c l"auil nu prcsque fatal. ct 129 patients-tcmoins ctaient apparies aux cas pour I' ilge, ht durfr du risque ct la gravitc de I' a,thmc Qugc par le bcsoin d'hospitalisatinn causee par l' asthme dans les deux annces prcccdcntes ). METHODES : Dcux cliniL·iens (Jill p:1sse L' ll revue le lrailellll' lll qui avail etc prcsnil it ccs 258 .,ujcts pendant lcs dell\
ASTIIMA MORllllJITY .\ND MORTALITY HAYE BEEN JN.
creasing in a nu111hn or countries despite recent seicnJilic· advances tlwt have i111proved the understanding of this chronic lung condition ( 1-3). The treatment or asthma has been identified as a pntcnt ial contributing factor to this increasing morbidity and mortality \4-6 ). In the past. phannacological treat111enl or asthma rocused nn hrnnchodilator therapy. hut the more recent recognitinn that chrnnic .1.~thma involvl's a characteristic inflammatory response in the airways has changed the therapeutic management or asthma {7 - \J ). This greater emphasis on anli-i ntl ammatory therapy and decreased reliance on bronchodilators alone is reflected in the revised guidelines for the lrcalmcnl of asthma disseminated to the medical community in written reports :is we ll as scientiriL· journals ( I 0- 13 ).
The primary objecti ve of'lhc present study was to estimate the potential impact that this change in emphasis might have by comparing pharmacolherapy in asthmatics with or without a life-threatening episode in Saskatchewan from I lJXO lo 1987. This was accomplished in two w,iys: first, by having two clinicians review clinical and drug treatment information 11n all cases or life-threatening a.,th111a aml a similar number ()f control patients with asthma who had not had a life-threatL'ning episode. and subsequently classify their pharmarnthcrapy as ·incnmpatible· or 'partially compatible' with u1rrcnt ph,mnacl 1thcrapcutic recommendations. as first formal i1cd in the Canadian A,lhma Guidel ines ( 12): and second. hy :1pplying an · Asthma Management Score· to each nf' the cases :ind selected cnnlrnls to obtain a numerical index of' the degree or "incompatibility" . A furtlll'r objective ol th is study w:1s to determine whether knnternl was more likely
Can Respir J Vol 2 No 1 Spring 1995
Overreliance on bronchodilators in asthma
il ll llCeS preccdentes Cl !'Olli cJassific L'lllllllle «i!lCll111pillihle» nu «compatible» (du moins partiellemcnt crnnpatihiL'l avec les lignes directrices en vigueur de la pharmarntherapie. En plus de celle classification. unc cote d 'cvaluatinn du 1rai1c-111cnt a cgalernen t etc appliqucc ii clwquc sujct participant il l'etude. Cette cote ctait basce sur J"utilisat iun d'agcnts anti inllammatoircs (par voie oralc ou par inhalation) en conjonctinn avec !'utilisation rcguliere de hronchodilatateur,. de merne quc sur !' utilisation de corticostcro'ides pour lcs patiL·nts qui venaienl de quitter J'h{1pital apres avoir soullert d ' unc crisc d' asth111c. RtSULTATS : Au moins un des dcux r0viseurs cliniciens a _jug0 le trai temenl inco111patihlc avec lcs nllrmcs en vigucur cha ,..FJ % des patients-L·as n imparativemcnl ;1 20 'It des sujets qui 11 • avaicnl pas suhi un cpi,q1dc 111ellanl !cur vie L'll danger. La moyenne ± ecart-typc de la cote du traitement eta it de 3.5± I. 7 pour les cas comparativemcnt ~1 0.8± 1.4 pour Jes tcmoins. indiquant quc la qualite du traitemenl phannacnlogique etait plus mauvaise chez lcs cas (P<0.001 ). CONCLUSIONS : Un traitemenl pharmacologique incompatible avec Jes rccommandations en vigueur etail plus courant chcz les cas d'asthmc fatal ct presquc fat al en Saskatchewan. de I 980 it 1987.
than alhutcrnl to ha\'C hcen prcsnihcd in subjects who \l\'l'r
rc ly nn hrn11chodil,ilms.
PATIENTS AND METHODS Overall study design: As previously repmlcd ( 14 ). a nestcc..l case-control design was used to cxami11L' the relationship between the use of bela-agonists :rnd lhL' risk of' death and nc:ll' de:1th lrnm asthma. Briclly. linked rll':dth insurance databases of' the province or Saskatchewan wnc used to identif'y a cohort of' 12.301 patients who were dispensed I 0 or more prescriptions for an :1sth111a rnediL·ation hL' l ween January I. 1978 and April 30. I l)87 . These mediL·ations were not avai lable without a prescription and a di spensing record was required for thl' pharrnaL·ist tii 11l' dirl'L'tly reimbursed by the government which pays fur all prescribec..l rncdications. Subjects had lo be between the ages of five and 5-t years during the study period (January I. ll)XO to April 30. 1987) lo be consiclerec..l al risk. Prcdetcrrnined criteria were used lo identily L·ase p:1til'nls who died ol asthma during the study period H-4 patients) or, lor those who su1'\'i vcd. experienced a near-fauil asthmatic episode (X5 patients ). A ncar-l'al,il event was definec..l as intubation. mechanical ventil ation . m PC02 greater than ..is mmHg during a hospit:ili zation f'or asthma. Up to eight controls were selected from ,1mong the n ilmrt of 12.30 I ,md were matched to each c;i.-;c patiL'nt on the basis of age at entry into the cohort. date or entry. the lll"l'UITCllCe of' a hw;pi tali1;1[ion rrn a.sthma in lhl' prior [WO
year~. region of' reside nce and rece ipt or soci,il assistance al any time during the study. In addition . the controls were l"L' l)Uircd lo ha ve been al risk for the llllll"OlllL' al the time of the cvrnt in the case p,tticnl. rcJ'errL·d to as the index
35
ERNST ET AL
TABLE 1 Asthma management score
Criteria Average number of beta-agonist inhalers per month
(prior 12 months)
>3
>2 S3
,::1.5 ::-2
<1.5
Points
3
2
1
0
Anti-inflammatory therapy' (number of prescriptions dispensed during prior 12 months)
none
<3 ):3 ·,11
>11
Use of contraindicated drugs t
within 1 month of index event or hospitalization for asthma
2 to 12 months before index event or hospitalization for asthma
Most recent acute attack requiring hospitalization within 12 months before index event not adequately treated
no corticosteroids
inhaled corticosteroids only
Maximum score
3
2 1
0
2
2 1
10
'Includes oral corticosteroids, inhaled corticosteroids, and inhaled cromolyn; t Includes beta-blockers. sedatives and parasympathomimetics
date. A tolal of 655 controls were matched to the 129 case patients .
Cl in ical information was obtained for all 129 cases and their 655 matched controls from two sources - hospital medical records and physician questionnaires ( 15). First, hospitali
zations with a primary discharge diagnosis of asthma during the two years preceding the index event or matching index date (not the hospitalization which might have ocrnrred at the time of the life-threatening episode) were identified from the
computerized databases. Abstractors, blind to the study hypothesis and unaware of the case/control status of the subjects, visited hospital medical record departments and. using a standard form. obtained information from the patients' charts on precipitating factors, presenting respiratory symptoms and their durati on. past history. si gns of a life-threatening atlack, lung function and arterial blood gases.
Second, the computerized out-patient physician datafile was used to identify physician visits by study subjects. Eligi
ble visits were those in which a general practitioner. pediatrician, internist. allergist or respirologist had seen the stu<ly subjects in the two years before the index date or event. Questionnaires were hand delivered by research personnel to these physic ians and were subsequently picked up on completion. Clinical information similar to that gathere<l from hospital medical records was sought from the ph ys icians.
Ethical approval was obtaine<l from the arrrorriate agencies of Saskatchewan Health . Study subjects for management classification: The subjects were the 129 cases of fatal and nc::ir-l'atal asthma pre-
36
TABLE2 Characteristics of study subjects
Number of subjects
Male(%)
Age (years) at index event
Number of office visits· to specialists to nonspecialists
Number of hospitalizations t
~~~~~~~~~~
Case patients 129
54
Controls 129
12
Mean ± SD 30i 15
10±11 35:t30
2.1 ±3.4
28+14
6±10 29:t25
1.1±1.3
'Visits were those made during the two years before the index event or date. Specialists included pulmonary medicine, allergology, pediatrics and internal medicine; t In which there was a primary or secondary diagnosis of asthma
viously i<lcntified, as described ,ibove. From the controls who were matched to each case . the first control per case was selected in whom similar c linica l information (ie, hospit al rccor<l information) was or was not available. This was undertaken to ensure that cases and controls were classifie<l accor<ling to comparable information. A total of 258 subjects WLTC
lherefore included in the analysis. Because controls were
listed by sex with !'cmalcs appL~aring firs t. they were more likely to be selected as controls for the presen t analysis. Methods for management classification: For each case and matched control a dossier of information was assembled. For the fatal case patients this included a copy of the death certificate, as well as autopsy and coroner reports when available. If the death occurred in hospital. a copy or the hospital di -·charge summary associa ted with the event was
also obtained. For the near-fatal case patients. a rnpy of the hospital <lischarge summary associated with the near-fatal episode was retrieved. In addition to the inflirmation surroundi ng 'the event'. additional clinical information was obtained from the hospital medical records for each case an<l
matc hed control who were hospitalized ror an asthma-related episode during the two ye,irs before the index event. as described above.
Detailed ex posure information regarding mc<lication <lispenscd each month fo r the 12-month period bcl'orc the index event or matching index date was also obtained for each case
patient and matched control from the Prescrirtion Drug Data Base uf Saskatchewan Health. One unit or an inhaled bctaagonist was equ ivalent lo the <lispcnsing or one mctrc<l <lusc inhaler (M DI). For other medications a unit rcprcsente<l the
dispensing of one prescription, usually a one-month supply. For the physician review, beta-agonists were identified by class only. an<l not by in<livi<lual generic names.
Each of the dossiers for the cases and their matched control was reviewed in<lcpen<lently by two cliniciaus experienced in the treatment of asthma. On the basis of the information available the clinicians classified the management or each subject as either 'incompatible· or ·at least partially nnnpatible' with the current emphasis in pharma
cotherary. These classifications were then collated to determine the number of cases and con1rols dassific<l as
Can Respir J Vol 2 No 1 Spring 1995
TABLE 3 Frequency of management classified as incompatible with current treatment guidelines in 129 matched pairs following clinician review
Classification Cases(%) Controls(%)
--~n- =_1_2_9},_ (n=129 ~ value* At least one clinician
classified treatment as incompatible
Both clinicians classified treatment as incompatiblet
63 (48 .8) 26 (20.2) <0.001
15 (11.6) 10 (7.8) >0 05
'McNemarx2 statistic; tThese subjects were included in the 63 cases and 26 controls classified as treatment incompatible by at least one clinician
TABLE4 Correspondence between classification by clinicians and asthma management score
Classification b clinicians Number (n=258 Mean score Classified as incompatible by
both clinicians 25 4.9
one of the two clinicians 64 4.0
neither of the clinicians 169 2.6
·incompatible' as judged by both reviewers, as well as the number classified as 'incompatible' as judged by al least one or the reviewers. No allempl was made to have the two clinicians judge the adequacy of pharmacotherapy in an equivalent way, and their assessments ,vcre cllTied out without knowledge of the other clinician· s judgement. Only gen
eral instructions were given as to the factors lo he considered. These were the use of high or increasing doses of hronchodilators, especially inhaled hcta-agonists. the undcrusc of inflammatory drugs and the use of contraindicated drugs. especially in relation to clinical events such as hospitalitations. It was felt that greater sensitivity to inadequacies in
pharmacotherapy might he obtained by keeping the clinical evaluations independent in this way. though al the price of a less adequate demonstration of the validity of such a clinical
assessment. To va lidate the suhjecti ve assessments made by the two
clinicians and to provide a more objective measure or the qua! ity of pharmacotherapy. an asthma management score was developed based on c urn.:nt pharmacological treatment guidelines (Table I) . This was considered necessary since the clinicians could not be blinded to the case control status. ie. the occurrence of a life-threatening event, and such knowledge may have resulted in their be ing more critical of the management in this g roup. The potential range for the management score was O lo I 0. with O reflecting pharmacological treatment most compatihlc with current guidelines, and 10 indicating treatment considered least compatihle. T his management setm .. ' was applied lo each of the cases and c1mtrols by another member of the research tean1. who was hlind to
the case and control status of each subject, using the same information the clinicians had reviewed. The weight given to
Can Respir J Vol 2 No 1 Spring 1995
Overreliance on bronchodilators in asthma
the different elements of the score are somewhat arbitrary. This is necessarily so. since it is dillicult lo equate the pre
scription of a contraindicated medica tion . for example, a beta-blocker. which occurred in one case, with a given level
or overuse of beta-agonists. However. the weights g iven for the different levels of use of heta-agonisls and anti-in fla mmatory agents are compatible with the dose-response relationships observed in the cohort of 12.JO I subjects with asthma. Analysis: The frequency of management incompatible with cu rrent pharmacotherapy. as classified by the two clinicians. was compared in the cases and controls using the Mc Ncmar
l . . ' . x- stat1st1c lor matched pairs. Till' 111c;111 asthma management
score was calculated for cases and controls. and the paired t test was used to determine whether there was a significant difference in the mean scores. In determining the association
between exposure to fcnoterol and albutcrol and management classified as incompatible. an unmatched odds ratio and 95% confidence interval were calculated. This was undertaken since the outcome of interest was now the management classification in cases and controls crnnhined.
RESULTS C haracteristics of study subjects are presented in Table 2.
While the case patients and the controls were similar with
respect lo age. consequent lo the way controls were selected a larger percentage of the cases were males (54'-4,) than in the cuntrnls ( 12'/, ). \Vhcn examined in the cohort of 12. '.10 I patients as a whole. sex was not associated with outcome ( life-threatening episode of asthma). Furthermore. in the study sample, there was no sex difference in the type ll!'
quantity of pharrnacotherapy received . The present authors arc. therefore. confident that the sex difference bt'lween cases and controls Jiu not bias the results presented here. The case
patients used the services or physicians and were hospitalized more frequently than the control. .
The frequencies uf management classified as incumpal
ible \Vith the current emphasis in phannacolherapy. as determined hy the two clinician reviewers , arc presented in Tahk
.3. A significantly higher proportion of cases (suhjeels who had died of asthma. or experienced a near-fatal asthmatic episode ) than controls from each matched pair were classified as receiving treatment incompatible with current guidelines hy al least one of the two clinician reviewers (P<().()() I). Fur the situation in which holh the clinicians classified the subject as recei ving treatment incompatible with current
guidelines, the di ffe rence between the cases and contrnls did not achieve s ta tistical significance (P>0 .05), at least in part clue to the small number of subjects classified in this way. Note that the 63 cases and 26 controls el assified as havi ng incompatible treatment hy at least one clinician included the 15 cases and IO controls classified as such hy both clinicians.
The result., or the asthma management score that was applied lo each nl' the case and contrnl subjects revealed a score ranging from O lo 8 for cases. and O lo 7 for controls. with IO being the maximum score possihle. The cases had a
statistically significant higher mean score (3 . .5) than did the
37
ERNST ET AL
TABLE 5 Association between clinical classification of overreliance on beta-agonist and being dispensed fenoterol or albuterol in the prior 12 months
Fenoterol Yes
No
Overreliance on beta-agonists*
Yes No Yes No
I 9 47 Albuterol Yes 116- 168
16 186 No I 9 65
Odds ratio 2.2 95% Cl 0.94 - 5.13
Odds ratio 0.69 95% Cl 0.29 - 1.62
'As judged by both clinicians. Cl Confidence interval
controls . (2 .8; f><(J.0002. 95'1, conl'it.!cnn' interval (U to I. I). with a higher score rcl'lectivc or plrnrn1acological treatment less compatihlc with current phannacothcrapy. The corn> spondrncc hetwecn the classification or treatment hy clini cian rcviL'W and that or the asthma rn,magemcnt score is provided in T,1hk 4. The average scores arc consistent with the clinicians' classification - a higher rne,1n score (rellect ivc of pharmacological treatment less co111p,1tihle with current guidelines) corresponding to subjects who were· class ified as incompatihle with current guidelines hy hoth clinician ,rvicwers. or hy one alone compared with suhjccts whose treatment was cla.,siried as at least partially compatible with the current emphasis in pharrn(tcotherapy.
Table 5 examines the relationsh ip between the li ke lihood ora suhjcct·s treatment heing classified as incompatible with current pharmacothcrapy by both clinicians and whether they had been dispensed l'cnotcrnl rather than albuterol in the prior 12 months. The small number or subjects precludes achieving statistical significance. The trend towards a positive association het\wcn being dispensed l'cnoteml and being classified as overreliant on bronchlldilators as opposed to the possible negative associalilln hct ween alhutcrol and appropriateness of drug therapy suggests. however. that these two inhaled bcta-agoni sts were used in patients in whom the quality of therapy was dif!crcnt. It may also suggest, in accordance with lhe results of Scars (5). that prescribing rcnoterul may worsen the severity of the di sease. which in turn would lead to a greater need rnr. or reliance on . b•·onchodilators.
DISCUSSION In response to increasing asthma morbidity and mortality
in many parts of the world. various nrgani1ations have brought together ex perts in the treatment of asthma to develop guidelines for asthma 111anagemL:11t in the hope of favourably int'luencing prognosis in this L'OlllllHHl disorder ( I 0-13 ). An important aspect of these guide! incs is the greater emphasis placed on early use or anti-inl'lammatury therapy and less relianee on hronchodi lat or therapy. This current emphasis in phannacothcrapy is based on several long term studies recently demonstrating the efficacy or inhaled steroids in decreasing asthma morbidity ( 9. I()- I 8 ). suggestive cvidcnCL' that regular use of brnnchodilators may actually make asthma worse (5.(1.19-21) and the strong a ·sociation
38
between mcrusc llr inhaled beta-ago ni .sls ,llld li fe -threatening asthma ( 1-J.). In an attempt to est imate thL~ impact on asthma morhit.!ity that might result from this change in emphasis in the phann:1cothcrapy of asthma. we evaluated the drug therapy received by asthmatic subjects who had CXPL'rienccd a lire-threatening atlad. and compared it with subjects of the same age and asthma severity who had not experienced a lite-threatening episode. Nearly half' of the cases nr life threatrning asthma were judged by at least one clinician experienced in the treittlllL'nl or aslh111,1 to have received treatment that did not at least partially meet L'lllTL'ntly rcco111-rnended therapy , compared with 20% of study subjects who did not experience such a life-threatening event. The 1110,t common pattern observed was the increasi ng use of various bronchodilator.s llVLT time without any dispensing of prcvcnli vc or anti-inrlammatory therapy ( 22 ).
To rende r the evaluation of therapy more objective. we LiL'vclopcd a management score that was then applied to the treatment regimens by an observer not experienced in the treatment of asthma. The score was formulated to re llcct the hypothesis that excess ive therapy with inhaled bcta-agonist bronchodilators without umum1itant use of anti-inflammatory therapy is ill -advised. Again. according to this score. cases of life-threa tening asthma dcrnonslrntcd greater divergence from current 1'L'co111111cndations than subjects who had not experienced such attacks. ;\s one would L'XJ)L'cL since bolh the score and the clinical a.-;scssment arc based 011 current standards of therapy, the score is higher among subjects in whom clinicians thought the therapy did not meet these standards. This provides some val idation of'thc clinical assessments.
We and others (23) have reported a stronger association between fenotcrol, as opposed to alhutcrol. use and fata l asthma. Such a di ffcrcnce might be explained i r subjects who were prescribed fenoterol were at a greater baseline risk of an adverse even t. Inasm uch as not being di spensed therapy that rellects current recommendations is a marker or increased risk. subjects dispensed fenotcrol appear to be at greater risk. Such channelling or therapy to different risk groups has been l'uund for fcnotcrol in another population (24). Our cvidcncL'. for such di llcrcntial prescribing can only be cons idL'1wl as pre liminary given the low statis tica l power available for such an analysis. This study was based un lhc L'xamination or computer and clinical records of inror111ation collected in the past. This li mits the amuunt or detail available on nonpharmaeological therapy as well as on environmental risk factors for life-threatening :1sthma. If such !'actors were associated with the pharmacotherapy di spensed in a different way in patients with a life-threatening episode or asthma than in those without such a history. these factors could partly explain the relationships dcsnibed.
CONCLUSIONS The rc~ults presented show that cases ex periencing fatal or
near-fatal asthma were more likely than controls to have rece ived inadeq uate therapy as judged by l'IIITL'nt treatment guidelines (spec ifically less anti-inflammatory and more
Can Respir J Vol 2 No 1 Spring 1995
hera-agonist treatment). From thi ., evidence. we suggest thal less rel iance on bronchrnJilators and greate r use of antiinrlammatory therary may have a positive impact tlll ,1sthma morbidity.
ACKNOWLEDGEMENTS: This study was supported by a grant from Boehringer lngc lheim Canada Inc. The study is based. in part. on data pmvi<le<l by the Saskatchewan Deparlmcnl or Hca llh. The inte rpn: talion s an<l conL·lu sions containc<l he rein uo not necessarily rcprcsL'nl those of the Government of Saska tchcwan or the Saskatchewan Dcpartmcnl or Healt h.
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Overreliance on bronchodilators in asthma
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