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Economic burden of asthma: a systematic review Bahadori, Katayoun; Doyle-Waters, Mary M; Marra, Carlo; Lynd, Larry; Alasaly, Kadria; Swiston, John; FitzGerald, J M May 19, 2009

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ralssBioMed CentBMC Pulmonary MedicineOpen AcceResearch articleEconomic burden of asthma: a systematic reviewKatayoun Bahadori1, Mary M Doyle-Waters1, Carlo Marra2, Larry Lynd2, Kadria Alasaly3, John Swiston4 and J Mark FitzGerald*4Address: 1Centre for Clinical Epidemiology & Evaluation (C2E2), UBC, Vancouver, BC, Canada, 2Faculty of Pharmaceutical Sciences, UBC, Vancouver, BC, Canada, 3British Columbia Centre for Disease Control (BCCDC), Vancouver, BC, Canada and 4Department of Medicine, Respiratory Division, UBC, Vancouver, BC, CanadaEmail: Katayoun Bahadori - Cbahadori@yahoo.ca; Mary M Doyle-Waters - mimi@interchange.ubc.ca; Carlo Marra - Carlo.marra@ubc.ca; Larry Lynd - llynd@interchange.ubc.ca; Kadria Alasaly - kadria.alasaly@bccdc.ca; John Swiston - swiston@interchange.ubc.ca; J Mark FitzGerald* - markf@interchange.ubc.ca* Corresponding author    AbstractBackground: Asthma is associated with enormous healthcare expenditures that include bothdirect and indirect costs. It is also associated with the loss of future potential earnings related toboth morbidity and mortality. The objective of the study is to determine the burden of diseasecosts associated with asthma.Methods: We performed a systematic search of MEDLINE, EMBASE, CINAHL, CDSR, OHE-HEED, and Web of Science Databases between 1966 and 2008.Results: Sixty-eight studies met the inclusion criteria. Hospitalization and medications were foundto be the most important cost driver of direct costs. Work and school loss accounted for thegreatest percentage of indirect costs. The cost of asthma was correlated with comorbidities, age,and disease severity.Conclusion: Despite the availability of effective preventive therapy, costs associated with asthmaare increasing. Strategies including education of patients and physicians, and regular follow-up arerequired to reduce the economic burden of asthma.BackgroundAsthma is an inflammatory disorder of the lungs thataffects people of all ages and is a significant source of mor-bidity and mortality worldwide [1,2]. Approximately 300million people in the world currently have asthma andrecent decades have shown a concerning increase in theprevalence of this condition in both children and adults(Figure 1). There has been concerning increase in the prev-alence asthma in both children and adults) [3]. If the cur-The economic costs associated with asthma are estimatedto rank as one of the highest among chronic diseases dueto the significant healthcare utilization associated withthis condition. Numerous studies have been publishedevaluating the economic burden of asthma on society andindividuals. However, a systematic review of the financialimpact of asthma has not yet been performed [5-8]. Thegoal of this systematic review is to evaluate and synthesizethe current literature regarding the economic burden ofPublished: 19 May 2009BMC Pulmonary Medicine 2009, 9:24 doi:10.1186/1471-2466-9-24Received: 12 November 2008Accepted: 19 May 2009This article is available from: http://www.biomedcentral.com/1471-2466/9/24© 2009 Bahadori et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Page 1 of 16(page number not for citation purposes)rent trends continue, it is estimated that there may be anadditional 100 million more asthmatics by 2025 [4].asthma. The evaluation of the cost of asthma from both asocial and economic perspective is necessary for an opti-BMC Pulmonary Medicine 2009, 9:24 http://www.biomedcentral.com/1471-2466/9/24mal allocation of resources as well as the betterment ofpatient care. This study sought to address the followingquestion: "What are the direct, indirect (productivity),and overall costs associated with asthma?"MethodsLiterature SearchA systematic review was conducted to identify English lan-guage articles published between 1966 and January 2008in which the costs of asthma were included. Only studiesreported in English (as there was no translator available)and published literature, were included.The following electronic databases were searched usingMEDLINE, EMBASE, Cumulative Index to Nursing andAllied Health Literature (CINAHL), Cochrane Database ofSystematic Reviews (CDSR), Health Economic EvaluationDatabase (OHE-HEED), and Web of Science. Search termswere investigated, including: "asthma", "direct servicecosts", "cost of illness", "cost- benefit analysis" and"health care costs". Duplicate citations were identifiedand removed using RefWorks online bibliographic man-agement tool.Study SelectionThe titles and abstracts of all publications identifiedthrough the primary literature search were independentlyreviewed by two investigators. The inclusion and exclu-sion criteria used for study selection are outlined in Table1. The total of four non-English abstracts were retrievedand excluded from the literature search. The full text of allpotentially eligible papers determined after the first levelof screening was reviewed to ensure that each paper metthe inclusion criteria for population and outcomes ofinterest.The types of cost related to illness were divided into directand indirect costs and were defined as follows: direct costsrelated to direct health service costs and included alterna-tive treatment/medications, physiotherapy/chiropractic,peak flow meters, primary care consultations, paid helpfor housekeeping, hospital emergency and outpatientattendance, ambulance and other transportation, andhospital admissions. Indirect costs were those applicableto individual patients, their families, and lost opportuni-ties for work or education. The total cost is an aggregate ofboth direct and indirect costs. For cost data from theUnited States (US), costs were converted to 2008 US dol-lars using the medical care component of the consumerprice index from the US Bureau of Labor Statistics.For cost data from non-US countries, figures were firstconverted to 2008 currency values using that country'sconsumer price index. Figures were then converted to2008 US dollars, using currency exchange rates of Austral-ian dollar (AUD)$1.00 = United States dollar(USD)$0.637, Canadian dollar (CAD) $1.00 = USD$0.806, (Euro currency code) EUR€1.00 = USD$1.281, andGreat Britain pound (GBP)£1.00 = USD$1.427. If the yearof the cost data was not reported, it was assumed to be thepublication year of the article. In all cases, both the origi-nal cost figures provided in the publications as well as theequivalent costs in 2008 US dollars were reported.Data AbstractionA standardized data abstraction form was used for all pub-lications included in this study. The data abstractedTrend in prevalence of asthmaFigure 1Trend in prevalence of asthma.Table 1: Inclusion and Exclusion CriteriaInclusion Criteria Exclusion Criteria• English language • Conference abstracts, case reports, letters, comments, editorials and review papers• Studies that consider the costs of asthma from either the individuals', the health services', and/or society's perspective• Studies that consider asthma with other comorbidities (such as allergies, COPD, etc)• Pharmacodynamic or pharmacokinetic studies• Studies that did not quote costs in the results section• Animal or in vitro studiesPage 2 of 16(page number not for citation purposes)BMC Pulmonary Medicine 2009, 9:24 http://www.biomedcentral.com/1471-2466/9/24included the following information: manuscript authors,year of publication, study design and duration, patientcharacteristics (population, age and gender), method ofcost calculation, direct costs, productivity (indirect) costs,and total costs. Discrepancies in data abstraction wereresolved by consensus.Methodological Quality AssessmentThe quality of the economic studies was assessed using acustomized version of the Drummond and Jefferson crite-ria (Table 2) [9]. Quality criteria were scored as positive,negative, or unclear. Study quality was assessed by onereviewer and confirmed by a second reviewer. Economicevaluations that scored 50% or more of the items positivewere defined as studies of high methodological quality,whereas less than 50% was considered low methodologi-cal quality. The 50% score was arbitrarily chosen as amean cutoff to create binary categories.Statistical AnalysisDue to the heterogeneity in cost analysis and reportingacross the studies, a quantitative meta-analysis to aggre-gate cost data could not be performed. Specifically, theresources used to derive direct healthcare and productivitycosts varied substantially between the studies, as did thetype of currency (USD, GBP, CAD, etc). In the absence ofthe ability to complete a meta-analysis, we opted to com-plete a qualitative analysis. There were not sufficienthomogeneity in terms of participants, interventions, andthe way outcomes were defined and measured, to providea meaningful summary for considering the meta-analysis.ResultsLiterature SearchThe primary literature search identified 2,976 citations.After removing duplicate citations we were left with 2,073unique citations for screening. The manual screening ofall 2,073 titles and abstracts yielded 307 articles that con-tained primary clinical data evaluating the cost of asthma.Of the 307 full articles retrieved and reviewed by theinvestigators, 68 met the inclusion criteria (Figure 2).Quality AssessmentMost of the studies clearly described the inclusion andexclusion criteria and the population as well as specifyingthe primary outcome measures. The study designs werecohort (n = 43), cross- sectional studies (n = 22), and case-control studies (n = 3). Of the 68 studies, only six com-pleted sensitivity analysis [10-15]. Common perspectivesof an economic evaluation were the societal perspective(all costs and outcomes experienced by all those who aresignificantly affected by the intervention) and the health-care perspective (only health costs and outcomes). Thirty-two studies mentioned the perspective (all societal) of theeconomic evaluation [10-43]. Twenty-six studies calcu-lated both direct and indirect costs, which suggests,although not explicitly mentioned, that these studies alsoadopted a societal perspective. Ten studies only calculateddirect medical costs and thus, adopted a healthcare per-spective. Three studies calculated an incremental costeffectiveness ratio (ICER) [10,19,21]. The uncertainty ofthe outcomes was presented through sensitivity analysesin six studies [10-15]. The mean score of the qualityassessment regarding the economic evaluation was 6.1out of a maximum of 10 (Standard Deviation (SD) 1.43;range, 3 to 9).Characteristics of the Selected StudiesOf the 68 studies identified in the literature review,twenty-three used data derived from the US, twenty-fivefrom European countries, eight from East Asia and thePacific regions, five from Canada, and seven were fromother countries. Twenty-eight studies reported mean ormedian per patient direct and indirect costs of asthma,thirteen only reported the total direct costs of asthma, andfifteen studies reported annual or total asthma relatedhealthcare expenditures. The economic impact in fivestudies was based on charge data (not costs) [25,44-47].The studies presented in this review used several methodsof cost calculation. The most common method was toabstract mean patient resource utilization, such as thenumber of clinic visits, hospitalizations and procedures,Table 2: Criteria for evaluating an economic analysis based on Drummond and Jefferson assessment method*1. Was a well-defined question asked in an answerable form?2. Was a comprehensive description of the competing alternatives provided?3. Was there evidence that the program's effectiveness was established?4. Were all the important and relevant costs & consequences identified?5. Were costs and consequences measured accurately with appropriate physical units?6. Were costs and consequences credibly valued?7. Were costs and consequences adjusted for differential timing?8. Was an incremental analysis of costs and consequences of alternatives performed?9. Was a sensitivity analysis performed?10. Did the presentation and discussion of the study results include all issues of concern to users?Page 3 of 16(page number not for citation purposes)*Note: All items have three possible responses, Yes (+), Cannot tell (N/A) and No (-).BMC Pulmonary Medicine 2009, 9:24 http://www.biomedcentral.com/1471-2466/9/24through chart reviews or insurance databases, and to com-bine these data with the mean unit costs of each resource,derived from local or national accounting databases. Analternative method was to follow a cohort of subjects viaa cost-accounting system to capture the charges or costsincurred over time in the management of asthma symp-toms.Direct Versus Indirect Costs of AsthmaCost of asthma includes the components of both directand indirect costs. Direct costs include inpatient care,emergency visits, physician visits, nursing services, ambu-lance use, drugs and devices, blood and diagnostic tests,research, and education. Indirect costs or morbidity costsinclude school days lost, traveling, waiting time, and lostproductivity for the caretaker of asthmatic children. Directcosts have been shown to exceed indirect costs, and themajor components of the direct medical costs found werepharmacological expenditures and hospital admissions.An increase in direct medical costs can potentially lead toa reduced total cost of care if it results in a disproportion-ately greater reduction in indirect costs due to improvedclinical outcomes. In our systematic review, nine studieshave found that the direct cost of asthma accounted forthe greatest part (53–100%) of the overall cost[11,14,18,29,42,47-50] (Table 3). Of these, five were con-sidered high quality studies. However, some of thereviewed cost-of-illness studies estimated the healthcarecosts associated with asthma, but they took the broadersocietal perspective and also included the impact of mor-bidity and mortality on employment, productivity andother social costs. In five studies, the indirect costs greatlyexceeded the direct costs [13,17,22,51,52]. The quality ofResults of systematic literature searchFig re 2Results of systematic literature search.Total citations identified(n= 2976) Potentially relevant studies (n=304)x Asthma with other comorbidities xNon English text xConference abstracts, case reports, letters, anonymous authors, comments, meta-analysis, editorials and review papersIncluded Studies (n=68)Studies that met the inclusion criteria (n=177) x No cost analysisxNo Pharmacodynamic or pharmacokinetic studiesxNo asthma management or asthma intervention studiesTable 3: Studies were direct cost exceeded indirect cost of asthmaReferences No.Country Study durationSample size Total direct cost/personMean annual direct cost/person% Total indirect costTotal cost Mean annual cost/personInstitutional studies11 US 1 yr 401 - 3,307 65 1,801 - 4,15818 Canada 1 yr 149 196,898ϕ - 74 67,729 264,627 -- - - - -42 Canada 1 yr 339 - 1,200 x 88 157 - 1,357752 y 100 - 75285 z 56 66 151Regional studies47 Australia 1 yr 1.2 m 273 - 77 81 354 -National studies14 US 1 yr 4.7 m 7,301 - 88 955 8,256 -29 Canada 1 yr N/A * 397 - 61 257 654 -48 Switzerland 1 yr N/A * 860 - 61 553 1,413 -49 US 1 yr N/A * 3,822 - 53 3,367 7,189 -58 US 10 yrs 14.2 m 8,665 - 57 6,583 15,248 -All costs are converted and adjusted into 2008 US dollarsCost in regional and national studies are in million of dollarsΦ: of total study sample size, x = societal perspective, y = ministry of health perspective, z = patient perspectivePage 4 of 16(page number not for citation purposes)m: million; yr: year; N/A*: data not availableBMC Pulmonary Medicine 2009, 9:24 http://www.biomedcentral.com/1471-2466/9/24all but one of the above studies was also high [51] andindirect costs accounted for 52–75% of the overall costs(Table 4).Direct Cost of AsthmaHospital AdmissionIn this systematic review, the largest amount of direct costsfound were those allocated to in-patient hospitalization,accounting for 52 to 86% of the overall asthma-relatedcosts in seven studies, [28,30,38,42,53-55] and 47 to 67%of total direct costs in another five studies [14,15,20,48,49] (Table 5).There are several factors that can contribute to higher totalhospital costs. Two studies found the following variablescorrelated significantly with higher hospital costs: olderpatients, significant comorbidities, intensive care unit(ICU) admission, increasing severity, and prolongedlength of stay. In both studies, a small proportion of asth-matics accounted for a large proportion of the total hospi-tal costs [36,56]. A similar result has also been observed inanother study, possibly because of poorly controlledpatients with more severe asthma [14].Stanford and associates reported resources such as nursingcare, respiratory therapy, and ED-specific supplies alongwith equipment use and physician fees to account for themajority of hospital costs of asthma; 44%, 11% and 53%of the costs, respectively [36]. The results of the cost esti-mation for asthma hospitalization in Quebec for the year1994/95 indicated that of the total cost of $23.3 million,the greatest proportion was accounted for by pediatricpatients ($11 million) [57]. Similar findings in a retro-spective cohort study also suggested that although teach-ing hospitals in their study were not found to have highercharges, children's hospitals appeared to be more expen-sive due to the inherent responsibilities of a teaching hos-pital, but also due to the fact that they act as regionalreferral centers with specialized services for children [25].A patient's characteristics can also affect the cost of hospi-talization. In a study conducted in France, the cost of ahospital stay was compared between a well-managed asth-matic group and a poorly managed one before hospitali-zation based upon guidelines (11 criteria judged byexperts). The poorly managed group was older, tended toinclude more smokers, spent half as much time in ambu-latory care, and had a shorter length of hospitalization.The cost of a hospital stay was found to be 1.72 timeshigher in the better managed group, due mainly to the dif-ferences in the length of the hospital stay. However, in theunmanaged group, non conformity to the treatment forthe attack resulted in a cost excess ($4,900 vs. $4,065 p <0.05) [58].Over a ten-year period in United States, hospital inpatientcare represented the largest component cost of direct med-ical expenditures in 1985. However, in 1994, medicationswere reported to be the largest component cost of directmedical expenditures. The annual estimates increasedfrom approximately $1.4 billion (1985 adjusted dollars)to $2.5 billion. This increase was due to an estimated103.2% increase in total number of prescribed medica-tions and an estimated 169.3% increase in average unitcost per medication [50].Asthma Cost and Hospital CharacteristicsOur review showed that there are associations betweenasthma-related costs and the stratification of hospitals bygeographic region, ownership, location, and teaching sta-tus. In this systematic review, five studies explored therelationship between hospital "characteristics" and thecost of asthma. A large, comprehensive administrativedatabase examined the association of selected hospitalTable 4: Studies were indirect cost exceeded direct cost of asthmaReferences No.Country Study durationSample size Total indirect costMean annual indirect cost/person% Total direct costTotal cost Mean annual cost per personInstitutional studies13 Spain 1 yr 333 - 2,749 69 1,221 - 3,97017 Italy 1 yr 500 - 1,068 52 970 - 2,03822* US 1 yr 638 - n/a 55 488 - 72750 Denmark 1 yr 115 822,067 - 67 402,668 1,224,735 -National studies51 Germany 1 yr 52,794 n/a - 75 - 4.43 b -Page 5 of 16(page number not for citation purposes)All costs are converted and adjusted into 2008 US dollars* n/a: data not available; b: billion; yr: yearBMC Pulmonary Medicine 2009, 9:24 http://www.biomedcentral.com/1471-2466/9/24characteristics with cost among pediatric patients withasthma and its severity by hospital type in the state of NewYork. Hospital types were classified into teaching versusnon-teaching and private versus public. They reported themean cost of asthma to be higher in private hospitals,($1,868 vs. $1,771) and non-teaching hospitals ($1,876vs. $1,528). Although after adjustments for patient andhospital covariates, the differences in mean cost betweenpublic and private hospitals did not remain significant[59]. In contrast, a high-quality study conducted at ateaching hospital in an urban setting in Canada, foundtotal operating expenses per in-hospital patient day to be$681.70 for teaching hospitals and $496.81 for non-teaching hospitals, for the fiscal year 1990 to 1991 [18].However, in another cohort study, after adjusting forpatient and hospital characteristics, they found no differ-ences in hospital charges between teaching and non-teaching hospitals [25].In a cross-sectional study, the mean total charges, afteradjusting for significant covariates including severity ofmore, the average charges were found to be higher aturban teaching ($4,230) and lower at rural institutions($2,910) compared with urban non-teaching hospitals($3,424) [44]. However, a five year-population-basedstudy yielded contradictory findings regarding costs perhospital discharge. In this study, public hospitals reportedthe highest costs per discharge when compared with not-for-profit and for-profit hospitals ($656.84 vs. $514.08and $411.95, respectively). They included the asthmapatients discharged with referral to an outpatient unit,who generally had higher costs than those patients dis-charged who had made a full recovery [32].Asthma MedicationsMedications were found to be another major contributorto the cost of asthma. Eighteen studies reported "medica-tions" as forming the largest proportion of the direct costsrelated to asthma, accounting for 38%–89% of the totalcost [11,13,15,16,19,22,23,27-29,35,37,43,46,47,52,56,60] (Table 6).Table 5: Studies that represented inpatient care cost as the largest proportion of total direct cost or total asthma related costReferences No.Country Study durationSample sizeCost of inpatient care/person Total direct costTotal asthma related cost/personTotal asthma related costMean SD 95%CI %Institutional studies15 Canada 1 yr 940 614¥ - - - 1,421 - -28 Australia 1 yr 245 397 - - - - 779 -30 France 1 yr 17 ** 229 282.4 - 52 - - 6,85638 UK 1 yr 29* 439 816 0–2,895 57 - - 77342 Canada 1 yr 339 591 - - 77ψ - 766 -48 Switzerland 1 yr 589 928 - - 47ξ 1,779 - -52 Spain 3 mo 126 1,932 - 1,529–2,353 83 2,338 - -53 France 1 yr 94** 64,675ϕ - - 86 - - 745,847Regional studies54 US 1 yr 530,000 7.8 m - - - - - 20 mNational studies14 US 1 yr 4.7 m 4 b - 2 – 6 b 54 7 b - -20 Singapore 1 yr 27,164** 12 m - - - 25 m 346 49 m49 US 5 yrs 463,500** 1.6 b - - 67 4 b - 7.2 bAll costs are converted and adjusted into 2008 US dollars¥ from the societal perspective; * Number of the trial families admitted to hospital, out of 94 trials; **average number of hospitalization for asthma in one year; ξ: Hospital care found to be a major cost factor only in the adult group of the study;ψ: From ministry of health (MOH) perspective. It accounted 43% of total cost from a societal perspective;ϕ:of total study sample size; m: million; b: billion; mo: month; yr: yearPage 6 of 16(page number not for citation purposes)illness, income, and payer, were found to be significantlyhigher at investor owned ($4,203) as opposed to non-profit ($3,640) or public hospitals ($3,620). Further-In a large-scale study, the costs of asthma medication werefound to be the largest cost factor in children ($382.09 or41.3% of total direct cost) whilst it was reported as beingBMC Pulmonary Medicine 2009, 9:24 http://www.biomedcentral.com/1471-2466/9/24lower in adults. Furthermore, hospital care was found tobe a major cost factor in adult patients ($928.28,accounted for 46.5% of total direct cost) [48]. Besides age,severity of disease was found to be another factor affectingthe cost of medications. In a high quality study in Switzer-land between 1996 and 1997, the cost categories differedgreatly between those with and without exacerbations. Inthe latter, medication costs represented 70% while hospi-talization costs were 10% of total cost. However, in thosewith exacerbations, medication costs contributed only28%, but hospitalization costs contributed 63% of totalcosts [35]. Moreover, differences in the perspectives ofpatients, society, and the Ministry of Health could affectboth their behaviors and the asthma related costs. In twodifferent high quality studies, the cost of asthma in Can-ada was estimated from the perspectives of society, theMinistry of Health, and the patient. Hospital admissionsboth societal and the Ministry of Health's perspectives inthe second study [42]. However, medication costs werefound to be the largest single component of direct costsfrom the patient's perspective, in both studies [15,42].Besides hospitalization and medications, some patientswere shown to have much higher or lower costs, depend-ing on the actual utilization of medical services.Physician Visits/Outpatient ClinicOutpatient services provided by hospitals may be in theform of clinics, or be more similar in practice to a groupmedical practice within a hospital. These outpatient visitsprovide the same kind of care that is provided in a physi-cian's office; it is thus anticipated that the costs will be thesame. In a recent retrospective study, the largest propor-tion of direct costs was due to outpatient clinic costsTable 6: Studies that represented medication costs as the largest component of total asthma related costReferences No.Country Study durationSample size Cost of medication/person Total direct costTotal cost Mean annual cost/personMean SD 95%CI %Institutional studies11 US 1 yr 401 2,070 50 4,10113 Spain 1 yr 333 552 454 45 1,221 3,97115 Canada 1 yr 940 56¥ 8216 Italy 1 yr 446 240 181–299 47 ν 1,18619 Turkey 1 yr 118 1,388 109 81 1,71322 US 1 yr 638 141 53 ψ 488 72723 France 1 yr 234 - 60–75 ξ -27 Sweden 1 yr 220 463 56 822 0.62 b 2,65528 Australia 1 yr 245 55 89¢ 235 ¥35 Switzerland 1 yr 263 814 735 70 1,15655 Thailand 1 yr 183 72 111 47 154 §60 Estonia 1 yr 1,423 154,140ϕ 53 ψ 3.60 m 203Regional studies37 US 1 yr 25,614 - 38 67947 Australia 1 yr 1.2 m 147 m 54 273 m 354 mNational studies29 Canada 1 yr N/A* 164 m - 404 m43 US 1 yr 2.52 m 495 m 66 43 2.3 b51 Germany 1 yr 52,794 0.58 b 84 0.69 b 2.74 bAll costs are converted and adjusted into 2008 US dollarsCost information of study 46 was not available¥: From the patient's perspective; ¥: Total annual cost per person of asthma management to individuals; ν: 47% of mean annual direct cost per patient;¢ :The major component of the individual cost; N/A*: All asthmatic patients in 1990; ξ: 75% of stage 2&3 and 60% of stages 1&4 (the total amount is not available); §: hospital resource utilization; ψ: 53% of total medical expenditure; ϕ: of total study sample size; m: million, b: billion; yr: yearPage 7 of 16(page number not for citation purposes)were reported to be the highest component of total cost inadults from a societal perspective in the one study [15],and the highest component of total cost in children from(48.5%) and the majority (~76%) of this cost was due tocompleting pulmonary function tests (44%) and skin-prick tests (34%) [61]. Similarly, two other studiesBMC Pulmonary Medicine 2009, 9:24 http://www.biomedcentral.com/1471-2466/9/24reported "physician visits or office-based visits" to be thelargest expense of asthma related direct costs accountingfor 55–58% of direct costs [21,39]. Likewise, a cost-of-ill-ness study in United States over the 10-year period from1985–1994 reported an increase in total estimated annualasthma-related physician office visits combined with anincrease in the average charge per visit, which accountedfor an 82% relative increase in office visit expenditures[50].Cost of Asthma and Category of ServiceUnscheduled consultations found to be major compo-nents of primary care costs associated with the manage-ment of asthma. Prescribed medication for maintenancetreatment was also found to contribute significantly to thetotal asthma related costs. However, the results from stud-ies comparing these two services have given conflictingresults. In a large high-quality cohort study in eight coun-tries from the Asia-Pacific region, direct costs of asthmawere estimated as: total costs, urgent (unscheduled) ver-sus maintenance costs, and drug versus non-drug costs.The study reported that the urgent care costs were higherthan maintenance costs in the participating areas: Singa-pore, Hong Kong, Malaysia and China, representing 62%of the total costs [31]. In contrast costs of maintenancetherapy were reported to be more important in adults andchildren, respectively accounting for 67% of total healthservices in one study [62] and 55% and 73% of the totaldirect costs of treatment in another study [63]. None ofthe two latter studies were of high quality and thus, maynot be a true reflection of the overall economic impact ofasthma.Another cohort study classified the encounters into fourcategories of services: non-urgent outpatient visit, urgentcare visit, pharmacy refills, and hospitalization. This studyshowed that two-thirds of the asthma care costs wereattributable to non-urgent outpatient care and prescrip-tions; only one third were found to be attributable tourgent care and hospitalizations. This was possibly due tobetter access of enrollees to preventive asthma care, result-ing in fewer acute exacerbations requiring emergencydepartment (ED) visits or hospitalizations [33]. Similarly,a recent study conducted in Taiwan found that almostthree-fourths of asthma related costs was attributable tooffice and outpatient care; and only one-fourth wereattributable to urgent care and hospitalization. Theauthors felt their findings to be reasonable given the regu-lar clinical and follow up these patients received, whichdiminished the need for urgent care and hospitalization[40].Insurance Coveragereduced use of urgent or emergent care. Two studies inves-tigated the influence of insurance coverage on medicalresource utilization and costs. In the first, which was ahigh-quality cohort study, the patients who were insuredreported for every visit that they used more primary careservices (at higher costs) and less emergency departmentservices (at lower costs) than patients who were unin-sured. However, patients who were uninsured on somevisits were reported to have higher primary care, emer-gency department, and inpatient costs than patients inany other insurance category, suggesting a greater severityof illness among these patients. An additional reason isthat they also lacked insurance coverage to purchase moreappropriate controller asthma medications [39]. Simi-larly, in the second study, patients with supplementaryinsurance coverage reported a lower overall resource utili-zation rate. Total costs amounted to $2,446 for patientswithout supplementary insurance coverage and $2,092for patients with such coverage [64].Indirect Cost of AsthmaEconomic assessments of asthma included in thereviewed studies indicated that decreased productivity atwork and school represent a considerable proportion ofthe disease burden, specifically adding to indirect healthcosts. To accurately assess health-related work impair-ment, it is important to take into account both time lostfrom work, or absenteeism, as well as loss of productivitywhile at work. Productivity losses were measured as thedays lost from productive activities because of asthma, thedays that patients worked despite asthma symptoms(restricted days), and travel and waiting time associatedwith receiving outpatient asthma care. Twelve studiesincluded loss of productivity due to absenteeism fromwork/school as the largest single indirect cost [11,13-16,20,27,42,43,48,51,65], and loss of school/work dayswas found to be the largest category of indirect cost ineight studies [10,18,21-23,26,49,50] (Table 7). The indi-rect cost of asthma was not evaluated in eleven studies[19,30,34,35,39,54,62,64,66-68]. The quality of theeleven studies, except for two of them, was all estimatedto be above average.Children with asthma have much higher indirect coststhan the average child as the costs of parents missing workdue to the child's asthma is also an indirect cost. In a studyconducted in Hungary, high consumption of indirectresources was observed for both the adult and pediatricpopulation. However, the indirect costs represented amuch higher proportion of total costs for pediatricpatients compared with adult patients (52% vs. 21%).Furthermore, there was a statistically significant increasein the cost of lost work between parents of patients withPage 8 of 16(page number not for citation purposes)In this systematic review, we found that adequate insur-ance coverage in patients with asthma correlated with agood control and parents of patients with poor control[26].BMC Pulmonary Medicine 2009, 9:24 http://www.biomedcentral.com/1471-2466/9/24Cost of Asthma and the Associated Risk FactorsSeverityIn our systematic review, disease of greater severity, wasassociated with a higher total costs. Twenty-two studiessuggested more severe disease to be a major factor influ-encing the increase in asthma- related costs [11,13, 15,17,19,21,23,27,30,31,35,36,41,46,51,53,54,58,62,66,67] (Table 8). In two studies, the severity of illness was clas-sified into mild, moderate and severe categories. The firststudy, conducted in Spain, reported that the per-patientcost ratio of asthma increased to 1 to 1.5 to 2.6 for thethree levels of asthma. The second study, from US,reported that the per-patient cost ratios increased to 1 to1.4 to 2.4 for pediatric patients and 1 to 1.5 to 2.9 foradult asthma patients having good, moderate, and poorasthma control, respectively [13,26]. Similarly in a studyin the US over a two year period, asthma costs per patientwere found to be five times higher for those whose asthmawas categorized as severe than for those with mild asthma($1,579 vs. $298) on a per patient basis [67]. AnotherSpanish study revealed that the cost of a moderate asthmaexacerbation was 4-fold greater than that of a mild exacer-bation, and the cost of a severe exacerbation as much as 12times that of a mild exacerbation. The cost analysis,according to prior asthma severity, also indicated that thecost attributed to a patient with severe persistent asthmawas 2.2 times higher than that of an exacerbation in apatient with intermittent asthma. This indicates thatsevere exacerbations were found to be more harmful tothe patient and much more costly to the health systemregardless of the prior disease severity [53]. In one highquality study in the US, dividing patients with persistentasthma into mild, moderate, and severe categoriesshowed that the average annual direct cost of a patientwith severe, persistent asthma to be 1.3 times the cost of apatient with moderate, persistent asthma and 1.7 timesthe cost of a patient with mild, persistent asthma [21].Moreover, another high-quality study completed in Spainbetween 1994 and 1995 reported the costs of asthma forpatients with severe disease to be almost three-timesTable 7: Studies that represented loss of productivity due to absenteeism from work/school as the largest proportion of total indirect costsReferences No. Country Study duration Sample size Productivity loss/person Total indirect costTotal asthma related costMean SD 95%CI %Institutional studies10 US 1 yr 3528 83 - - - 148 -11 US 1 yr 401 1,370 - - 61 2,234 -13 Spain 1 yr 333 553,569 ϕ - - - 915,674 -15¥ Canada 1 yr 940 935 - - 92 1,018 -1,411 - - 50 2,836 -16 Italy 1 yr 527 416 - 261–573 53 663 -18 Canada 1 yr 149 44,623 - - - 67,729 -21 US 1 yr 443 1,437 3732 - - 1,788 -23* France 1 yr 318 - - - - -26 Hungary 1 yr 378 x 540 - - - 1,132 -711 y 170 - - - 810 -27 Sweden 1 yr 115 1,399 - - 76 1,778 -42 Canada 1 yr 339 66 - - 44 150 -50 Denmark 1 yr 115 760,853 ϕ - - 62 822,067 1.2 mNational studies14 US 1 yr 35000 315 m - 113–517 33 955 m 8,256 m20 Singapore 1 yr 142,300 18.5 m - - 37 24.31 m 49.36 m43 US 1 yr 2.52 b 821 m - - - 1,124 m 2.3 b48 Switzerland 1 yr N/A 414 m - - 75 551 m 1,413 m49 US 1 yr N/A 1,448 m - - - 4.2 b 7.2 b58 US 10 yrs 14.2 m 1,902 m - - - 6,583 m 15,248 mAll costs are converted and adjusted into 2008 US dollars* Cost information of studies 65 and 22 were not availablePage 9 of 16(page number not for citation purposes)¥: 92% from the patient perspective and 50% from the societal perspective; ϕ: of total study sample size; N/A: Number of asthmatics patients in US in 1985x: adult and pediatric patients, y: pediatrics; m: million; b: billionBMC Pulmonary Medicine 2009, 9:24http://www.biomedcentral.com/1471-2466/9/24Page 10 of 16(page number not for citation purposes)Table 8: Studies that found influence of severity on asthma- related costsSeverityIntermittent Mild Moderate Severe SubgroupsReferences No.Country Study durationTotal n n Cost n Cost n Cost n costInstitutional11 US 1 yr 401 - - 200 3339 137 5,716 64 16,16813 Spain 1 yr 333 - - 140 257,979 116 385,239 77 679,09115 Canada 1 yr 940 - - 1,799 2,466 4,344 Societal perspective- 256 744 459 862 225 1,192 Ministry perspective- 877 1,079 1,763 patient perspective19 Turkey 1 yr 118 4 202 54 1,006 46 1,954 14 4,08121 US 1 yr 3002 - - 787 5,390 1194 6,838 988 9,02023 France 1 yr 318 32 435 78 1,134 91 1,977 33 4,59827 Sweden 1 yr 115 53 359 62 4,47330 France 1 yr 261 - - 108 606 58 704 63 561 Good control- 1,184 808 1,426 Moderate control- 329 741 4,476 Poor control35 Switzerland 1 yr 422 14 511 31 1,440 42 3,487 72 5,22836 US 1 yr 3223 515 2,875 431 3,973 101 6,303 27 19,82046 Thailand 1 yr 511 - 104 - 125 - 182 - 22452 Spain 3 mo 126 - - - 515 - 1,926 - 5,54453 US 1 yr 1038 - - - 536 - 1,255 - 627 Good control- 354 651 200 1,119 347 1.214 Moderate control- 1,903 1,953 1,808 Poor control57 France 1 yr 169 66 3,942 53 4,608 Group P23 4,527 27 9,574 Group A62 Turkey 1 yr 183 - - 124 806 36+23 1,72967 US 2 yrs 2213 - - 1,007 463 237 374 969 2,36241 Australia 1 yr 193 No visits One visit/yr 2 Visits/yr >2 Visits/yr Urgent visit Hospitalizationn $ n $ n $ n $ n $ n $35 80 26 195 38 207 55 202 31 298 8 819Regional50 Denmark 1 yr 115 16 755 47 8,856 48 13,201 4 40,67717 Italy 1 yr 500 174 1,165 134 1,692 153 2,507 39 5,382National66 11 countries 1 yr 1201 - 1,143 - 1,113 - 1,213 - 1,48010 countries 1124All costs are converted and adjusted into 2008 US dollarsGroup P: not managed; group A: managed; * Cost information of studies 31 and 22 were not available.BMC Pulmonary Medicine 2009, 9:24 http://www.biomedcentral.com/1471-2466/9/24higher than for those with moderate asthma and five-times higher for those with mild illness [13]. In 1999, aretrospective cohort analysis of a representative data set of12,203 patients with asthma in the United Kingdom (UK)made a comparison of healthcare costs between patientswho had an asthma attack and those who did not. Averagetotal costs per patient was reported to be 3.53 times higherin the group who reported asthma attacks than in the non-attack group, indicating that the cost of managing patientswho experienced an acute asthma attack impinged heavilyon healthcare budgets [69]. Similarly, in a large-scaleSwiss study, total costs in patients with attacks were 2.38more compared with patients without attacks [48].Poor Asthma ManagementThe mean annual cost per patient increased as the level ofdisease control decreased. Seven studies reported that"poor asthma control" was associated with an increase inhealthcare and elevated costs [14,16,26,30,31,51,54](Table 9). All but one were rated as a high quality study.In a study by Lai et al, the relationship between asthmacontrol status, measured using a derived Asthma ControlTest (ACT) score, and utilization of healthcare and its costin eight Asia-Pacific areas were explored. ACT questionsasked patients to report for the previous four weeks, limi-tations to activities; shortness of breath; nighttime awak-ening; use of rescue medication; and perception ofcontrol. Completion of the ACT resulted in a potentialscore of between 5 and 25; a score of ≥ 20 indicated "well-controlled" asthma and a score of <15 suggested "poorlycontrolled" asthma. The mean per-patient annual cost ofasthma management for patients with a derived ACT of<15 was $861; $319 for patients with a derived score 15–19; and $193 for patients with a derived ACT score of ≥ 20.A higher derived ACT score was associated with a signifi-cantly lower annual expenditure on asthma management.This provides new evidence quantifying the link betweenasthma control and unscheduled healthcare resource useand cost. Poor asthma control was found to be associatedwith a greater likelihood for hospitalization and unsched-uled physician visits in the previous year. Not surprisinglyhigher asthma related costs were also found [31].Disability Status and Comorbidity ConditionsAn association between asthma patients with co morbidi-ties and higher costs was also found. Three studiesreported that costs increased significantly amongstasthma patients with comorbidities/comorbid conditions[24,35,54]. In a high quality study, diseases such as hemi-plegia, neurological disorders, psychosis, and acquiredimmune deficiency syndrome (AIDS), which were associ-ated with significant resource use in general, were foundto be highly significant cost drivers for the asthma cohort.More importantly, low-cost high prevalence diseases suchas lower respiratory tract infections were also found to besignificant cost drivers as well [34].The high costs among unemployed or retired patientsconstituted an important finding because these patientswere found to be most likely to have a poor overall prog-nosis in terms of morbidity and mortality. In a study con-ducted in Switzerland, the highest total costs wereTable 9: Studies that found increased cost of asthma associated with poorly controlled asthmaReference No. Country Study duration n Asthma control Cost stratified by severityLow Moderate High50 Denmark 1 yr 39 Well treated 8,94876 Poorly treated 11,52353 US 1 yr 515 Well treated 536 651 1,903294 Intermediate 1,255 1,117 1,954128 Poorly treated 627 1,214 1,80814 Italy 1 yr Well treated 593527 Poorly treated 2,09920 Hungary 1 yr 248 Pediatrics Well treated 97398 Intermediate 1,37410 Poorly treated 2,651352 Adults Well treated 554254 Intermediate 86188 Poorly treated 1,632Page 11 of 16(page number not for citation purposes)All costs are converted and adjusted into 2008 US dollarsCost information of studies 30 and 31 were not availableBMC Pulmonary Medicine 2009, 9:24 http://www.biomedcentral.com/1471-2466/9/24observed among jobless patients and those receiving disa-bility payments [63]. Similarly, in another study con-ducted in Canada, illness-related disability was found tobe the largest component of indirect costs ($76 million)[29]. In another high quality study, total costs amongworker's with asthma, with disability claims were reportedto be approximately three times higher than among disa-bility claimants in the employee control sample ($14,827vs. $5,280). Although treatment for asthma itselfaccounted for 16% or more of total costs, comorbid con-ditions accounted for an additional 13% or more. Forworkers with asthma, wage-replacement costs for work-days lost (40%) were found to be almost as much as med-ical care (43%) [10]. Similarly, in a high quality study,disability pensioners and homemakers were found tohave higher costs than severely ill patients [15].AgeAge was also found to have an association with the cost ofasthma, but there were conflicting reports. Younger agewas found to be a significant predictor of higher costs inseven studies [12,14,22,42,62,70,71]. However, sevenstudies reported "older age" to be significantly more likelyto have higher costs [15,27,36,39,54,56,58], or costs ofasthma to be increased as patients' age increased[35,45,48,52,60,66]. One study reported asthma-deriveddirect costs to be double in elderly compared to youngerasthma patients, mainly due to higher costs of hospitali-zation and medication [68]. Two other cohort studiesfound totally different results. The first, conducted in theUS, after stratifying patients into five age groups (5–9, 10–14, 15–19, 20–29, and 30–34) years, found that adoles-cents (15–19) years old had both lower inpatient and out-patient (primary care, urgent and nonurgent emergencydepartment services) costs than either younger or olderpatients (pvalue < 0.05 and pvalue < 0.01, respectively)[39]. The second, conducted in eight Asia Pacific areacountries, found extremes of age (<10 yrs and >60 yrs) tobe significantly predictive of higher asthma related costs[31].GenderGender was also found to have an association with thecost of asthma. Females were found to have higher directcosts than males, independently of the severity of diseasein three high-quality studies [13,16,37].RaceWe also found a correlation between race and the cost ofasthma. Identified Caucasian patients, particularlyfemales in a high-quality study over one year, were foundto have significantly more primary care visits (at highercosts) compared with African Americans [14]. In contrast,cantly more emergency department visits and costs com-pared with Caucasian patients [39].Other FactorsBesides disease severity, current use of preventive drugs,current use of emergency services and/or current hospital-ization was found to be the predictors of costs of child-hood asthma [62]. Not surprisingly ICU admission wasfound to be significantly associated, with higher total hos-pital costs [56]. A study in Canada reported smoking anddrug plans to be significant explanatory factors of highercosts from different societal, Ministry of Health, andpatient perspectives. The annual cost per patient in thisstudy varied from $1,255 in young non smokers with nodrug plan and mild disease to $5,032 in older smokerswith drug plans and more severe disease [15]. Statisticallysignificant predictors of higher total costs in another studyby Ungar (2001) were worse symptoms and season of par-ticipation [42]. Also, in another high quality cost of illnessstudy, use of peak expiratory flow rate meters, low-incomestatus, non-Caucasian race, and longer duration of asthmawere found to have a significant association with increas-ing cost [22]. Two studies reported free access to health-care as a significant risk factor for increased cost of asthma[30,53]. In addition, one study reported that costsincreased significantly with the occurrence of asthmasymptoms in the previous year as well as possible pre-scribed inhaled corticosteroids [54]. A cohort study in theUS found the number of β-agonists and oral corticoster-oid prescriptions to be significantly associated with highercosts [34]. A study in Switzerland reported use of control-ler therapy versus symptom relief medication and involve-ment of a pulmonologist in management was associatedwith an 80% and 30% increase in direct medical asthmacosts, respectively [35]. Another Italian study reportedasthma subjects, with chronic cough and sputum produc-tion to have higher costs compared to subjects without thesymptoms. Moreover, the risk of having high direct med-ical expenditures was reported to be significantly higherfor blue-collar workers as compared to workers of a highersocio economic status [16]. Finally, multiple regressionanalyses of the 2,052 exacerbations included in the eco-nomic analysis showed that the cost of exacerbations wassignificantly affected by country (P < 0.0001). Mean costswere found to be significantly higher in secondary care($1,994) than primary care ($657, p = 0.0003) [66].DiscussionEconomic evaluations of asthma have been performed inmany countries. But there are only limited populationbased studies. The studies reported here are difficult tocompare because of differences in study designs, defini-tions of costs, and different time periods. The present sys-Page 12 of 16(page number not for citation purposes)African-American females were found to have signifi- tematic review was aimed at identifying the evidenceBMC Pulmonary Medicine 2009, 9:24 http://www.biomedcentral.com/1471-2466/9/24concerning the economic burden of asthma, as there havebeen no other systematic reviews in the literature thathave reviewed this field and it is a highly emergent aspectof health-services management.Asthma is associated with enormous healthcare expendi-tures that includes both direct costs, in the form of hospi-talizations and medications, and indirect costs, in theform of loss of work which is a combination of directlymissed days of work/school that occur during the exacer-bation and the loss of future potential earnings associatedwith both morbidity and mortality.Indirect costs in some studies constitute a major portionof health related costs, and were identified to be higherthan direct costs in six studies [13,15,17,22,51,52]. How-ever, not all of the reviewed studies have evaluated theindirect costs associated with asthmatic patients. There-fore, additional studies are necessary to provide a clearerdescription of these indirect costs and their contributionto the total cost of care.In contrast, nine cost of illness studies reported that thedirect costs of asthma, associated with hospitalization ormedications, to be higher than the indirect costs ofasthma [11,14,18,29,42,47-50]. This may possibly beexplained by the costs of hospitalization and medicationas the most important cost among direct costs.The significant contribution of direct healthcare costs dueto hospitalization in studies is not surprising given theinherent high costs associated with acute care versusambulatory care [14,15,20,28,30,36,38,42,48-50,53-57,65,72]. Variations in the cost of hospitalization arelikely related to the differences in the socioeconomic envi-ronment, that is, the difference in the gross nationalincome per capita, or more specifically differences in sal-ary costs in different countries.The fact that the cost of asthma medications is the largestproportion of direct costs of asthma, is likely explained bythe fact that there are a relatively large proportion ofpatients with asthma of whom only a minority are admit-ted to hospital. In addition the combination of frequentuse, the higher cost of newer asthma drugs [11,13,15,19,22,23,27-29,35,37,43,46,47,52,56,60], the smallerproportion in hospital costs and the higher proportion inmedication costs seen in some studies could also point tobetter control of asthma. It also likely reflects a rise in theprevalence of asthma. Furthermore, lower hospital costscan partly be explained by an overall trend towardsshorter length of stay in hospital [52].ment charges reported in five reviewed studies might beexplained by the better access of patients to preventiveasthma care or fewer acute exacerbations requiring hospi-talization or emergency care visits [33,37,39,40,43]. Like-wise, the predominance of urgent costs might be due tothe poor control of the disease in countries where primarycare is less well developed, leading to more urgent health-care utilization.Hospital type and characteristics were reported to havebeen associated with differences in charges for asthmahospitalizations. Teaching hospitals were found to havehigher charges compared with non-teaching hospitals[44]. This is likely due to higher costs associated withteaching hospitals in terms of funding due to teaching andalso the overall higher acuity and greater likelihood ofmore complex patients being cared for in these hospitals.The higher costs associated with patients admitted tomedical centers and regional hospitals than other patientsadmitted to district hospitals can be explained partly bythe tendency of medical centers and regional hospitals toreceive a relatively higher proportion of patients sufferingfrom more serious illnesses than district hospitals [32].In contrast, two studies in the US found no significant dif-ferences in costs and charges between teaching and non-teaching hospitals suggesting that, even with the responsi-bility of providing education, research, and care for indi-gent patients, teaching hospitals are competitive in theirtreatment of asthma [25,59]. One possible reason con-tributing to the differences in costs based on hospitalownership might be attributable to a hospital's levels ofefficiency and also with the exception of mechanical ven-tilation of asthma patients; usual care of asthma patientsirrespective of location is not associated with a high levelof technology [32].Not surprisingly costs of asthma care were found toincrease in the presence of exacerbations and with diseaseof greater severity [11,13,15,17,19,21-23,27,30,31,35,36,41,46,51,53,54,58,62,66,67].The reasons that children with asthma reported higherhealthcare costs compared to non-asthma conditionscould be related to: higher use of ambulatory care andmedications for upper respiratory tract infections or con-ditions that can act synergistically with asthma (such asrespiratory infections, otitis, sinusitis, etc), the use of day-care centers, experiencing more severe asthma on averageand higher healthcare use in general, and misclassificationof asthma-related encounters as "non-asthma"[24,25,30,40-43,57,62,70,71]. However, for adults, thePage 13 of 16(page number not for citation purposes)The predominance of non urgent office and outpatientcosts compared to hospitalization and emergency depart-increased total costs and increased costs per affected per-son could be explained by either an increase in the sever-BMC Pulmonary Medicine 2009, 9:24 http://www.biomedcentral.com/1471-2466/9/24ity of asthma or a decrease in the use of effectivehealthcare resources. In elderly patients with comorbidi-ties, such as congestive heart failure, which may deterio-rate with asthma exacerbations, have been associated witha sharp increase in the costs derived from the disease[36,56,68].Several studies have investigated a variety of potential riskfactors associated with a higher risk of direct or indirectcosts of asthma including: both old and young ages,female gender, smoking, co-morbid conditions, chroniccough and phlegm, use of peak expiratory flow ratemeters, free access to healthcare, low-income status, non-white race, asthma symptoms in the past year, longerduration of asthma, controller therapy versus quick ther-apy, involvement of a pulmonologist in diagnosis or treat-ment, number of β-agonists and oral corticosteroidprescriptions, and whether inhaled corticosteroids hadbeen prescribed before. The findings that females withasthma spend more on annual asthma care than malesmight be because of a higher use of acute care facilities dueto inadequate medication and poor inhalation skills, or itmight be interpreted as females confronted with a chronicillness are more concerned than males and thus, seekmedical care more often and have more medicine pre-scribed.Three more recent studies have been reviewed in this sys-tematic review; however, their findings didn't contributefurther to the previous results [73-75].Despite the availability of effective preventive therapy,hospital admissions from acute asthma are increasing.This might demonstrate that patients with acute asthmaexacerbations continue to be treated inappropriately priorto hospital admission.ConclusionIn summary, asthma is not only associated with patientspecific impairment, but it is also associated with a signif-icant cost to society. The comparison of studies assessingdirect and indirect costs of asthma underscores importantfacts: hospitalization and medications have been found tobe the most important cost driver of direct costs, whilework/school absenteeism accounted for the greatest per-centage of indirect costs. The cost of asthma was found tobe strongly correlated with comorbidities, age, severity ofdisease, and some other factors. It was also found to varysignificantly by hospital ownership, location, and teach-ing status. A large variation of asthma control can partlybe explained by variation in guideline adherence to med-ication use and deficits of patients' management espe-cially as it relates to access to patient education. Particularplanned homecare are required to improve quality of lifeas well as decrease the economic burdens of asthma.AbbreviationsACT: Asthma Control Test; AIDS: Acquired immune defi-ciency syndrome; AUD: Australian dollar; CAD: Canadiandollar; CDSR: Cochrane Database of Systematic Reviews;CINAHL: Cumulative Index to Nursing and Allied HealthLiterature; ED: Emergency Department; EUR: The eurocurrency code; GBP: Great Britain pound; ICER: Incre-mental cost effectiveness ratio; ICU: Intensive Care Unit;OHE-HEED: Health Economic Evaluation Database; SD:Standard Deviation; UK: United Kingdom; USD: UnitedStates dollarCompeting interestsThe authors declare that they have no competing interests.Authors' contributionsKB edited and prepared the final manuscript for publica-tion. KB and KA were responsible for reviewing articles,judging their relevance, assessing their quality, andextracting data. MW assisted in literature search. 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Huang ZJ, LaFleur BJ, Chamberlain JM, Guagliardo MF, Joseph JG:Inpatient childhood asthma treatment: relationship of hospi-Publish with BioMed Central   and  every scientist can read your work free of charge"BioMed Central will be the most significant development for disseminating the results of biomedical research in our lifetime."Sir Paul Nurse, Cancer Research UKYour research papers will be:available free of charge to the entire biomedical communitypeer reviewed and published immediately upon acceptancecited in PubMed and archived on PubMed Central BMC Pulmonary Medicine 2009, 9:24 http://www.biomedcentral.com/1471-2466/9/24tal characteristics to length of stay and cost: analyses of NewYork State discharge data, 1995.  Arch Pediatr Adolesc Med 2002,156(1):67-72.60. Kiivet RA, Kaur I, Lang A, Aaviksoo A, Nirk L: Costs of asthmatreatment in Estonia.  Eur J Public Health 2001, 11(1):89-92.61. 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Lane S, Molina J, Plusa T: An international observational pro-spective study to determine the cost of asthma exacerba-tions (COAX).  Respir Med 2006, 100(3):434-50.67. Li JT, Xakellis G, Edell ES, Angstman GL: Concentration of health-care costs in asthma.  Am J Manag Care 1995, 1:137-40.68. Plaza V, Serra-Batlles J, Ferrer M, Morejon E: Quality of life andeconomic features in elderly asthmatics.  Respiration 2000,67(1):65-70.69. Hoskins G, McCowan C, Neville RG, Thomas GE, Smith B, SilvermanS: Risk factors and costs associated with an asthma attack.Thorax 2000, 55(1):19-24.70. Lozano P, Sullivan SD, Smith DH, Weiss KB: The economic burdenof asthma in US children: estimates from the National Med-ical Expenditure Survey.  J Allergy Clin Immunol 1999,104(5):957-63.71. Valovirta E, Kocevar VS, Kaila M, Kajosaari M, Koivikko A, KorhonenK, Linna O, Makela M, Remes K, Ben-Joseph RH: Inpatientresource utilisation in younger (2–5 yrs) and older (6–14 yrs)asthmatic children in Finland.  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J Investig Allergol ClinImmunol 2000, 10(6):334-41.Pre-publication historyThe pre-publication history for this paper can be accessedhere:http://www.biomedcentral.com/1471-2466/9/24/prepubyours — you keep the copyrightSubmit your manuscript here:http://www.biomedcentral.com/info/publishing_adv.aspBioMedcentralPage 16 of 16(page number not for citation purposes)


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