RESEARCH ARTICLE

Ohio Pediatric Asthma Repository: Opportunitiesto Revise Care Practices to Decrease Time toPhysiologic Readiness for DischargeJeffrey M. Simmons, MD, MSc,a,j Jocelyn M. Biagini Myers, PhD,b,j Lisa J. Martin, PhD,c,j Carolyn M. Kercsmar, MD,d,j Christine L. Schuler, MD, MPH,a,j

Valentina V. Pilipenko, PhD,c John W. Kroner, MS,b Hua He, MS,c Stephen R. Austin, BS,b Huyen-Tran Nguyen, MD,b Kristie R. Ross, MD, MS,e Karen S. McCoy, MD,f

Sherman J. Alter, MD,g Samantha M. Gunkelman, MD,h Pierre A. Vauthy, MD,i Gurjit K. Khurana Hershey, MD, PhDb,j

A B S T R A C T BACKGROUND: Large-scale, multisite studies in which researchers evaluate patient- and systems-level factorsassociated with pediatric asthma exacerbation outcomes are lacking. We sought to investigate patient-level risksand system-level practices related to physiologic readiness for discharge (PRD) in the prospective Ohio PediatricAsthma Repository.

METHODS: Participants were children ages 2 to 17 years admitted to an Ohio Pediatric Asthma Repositoryhospital for asthma exacerbation. Demographics, disease characteristics, and individual hospital practices werecollected. The primary outcome was PRD timing (hours from admission or emergency department [ED]presentation until the first 4-hour albuterol spacing).

RESULTS: Data for 1005 participants were available (865 ED presentations). Several nonstandard care practiceswere associated with time to PRD (P , .001). Continuous pulse oximetry was associated with increased timeto PRD (P5 .004). ED dexamethasone administration was associated with decreased time to PRD (P, .001) andless ICU admittance and intravenous steroid use (P , .0001). Earlier receipt of chest radiograph, antibiotics,and intravenous steroids was associated with shorter time to PRD (P, .05). Care practices associated with shortertime to PRD varied markedly by hospital.

CONCLUSIONS: Substantial variation in care practices for inpatient asthma treatment exists among children’shospital systems in Ohio. We found several modifiable, system-level factors and therapies that contribute toPRD that warrant further investigation to identify the best and safest care practices. We also found that therewas no standardized measure of exacerbation severity used across the hospitals. The development of such a toolis a critical gap in current practice and is needed to enable definitive comparative effectiveness studies of themanagement of acute asthma exacerbation.

aDivisions of HospitalMedicine, bAsthmaResearch, cHuman

Genetics, and dPulmonaryMedicine, CincinnatiChildren’s Hospital

Medical Center,Cincinnati, Ohio;eDepartment of

Pediatrics-Pulmonary,Rainbow Babies andChildren’s Hospital,

Cleveland, Ohio; fDivisionof Pediatric Pulmonology,

Nationwide Children’sHospital, Columbus, Ohio;gDepartment of Infectious

Disease, DaytonChildren’s Hospital,

Dayton, Ohio; hDivision ofPediatric HospitalMedicine, Akron

Children’s Hospital, Akron,Ohio; iDepartment ofPediatric PulmonaryMedicine, ProMedica

Toledo Children’sHospital, Toledo, Ohio;and jDepartment of

Pediatrics, Universityof Cincinnati College of

Medicine, Cincinnati, Ohio

www.hospitalpediatrics.orgDOI:https://doi.org/10.1542/hpeds.2017-0085Copyright © 2018 by the American Academy of Pediatrics

Address correspondence to Gurjit K. Khurana Hershey, MD, PhD, Division of Asthma Research, Cincinnati Children’s Hospital MedicalCenter, Cincinnati, OH 45229-3026. E-mail: gurjit.hershey@cchmc.org

HOSPITAL PEDIATRICS (ISSN Numbers: Print, 2154-1663; Online, 2154-1671).

FINANCIAL DISCLOSURE: Dr Simmons reports grants from the Patient-Centered Outcomes Research Institute outside the submitted work. DrsHershey and Martin report grants from the National Institutes of Health outside the submitted work. Dr Kercsmar reports personal fees fromGlaxoSmithKline outside the submitted work; the other authors have indicated they have no financial relationships relevant to this article to disclose.

FUNDING: Funded by the Ohio Department of Job and Family Services grant G-1 213-07-0561.

POTENTIAL CONFLICT OF INTEREST: Dr Kercsmar reports personal fees from GlaxoSmithKline outside the submitted work; the otherauthors have indicated they have no potential conflicts of interest to disclose.

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Asthma is the most pervasive chronicchildhood condition, affecting more than7 million US children.1 Hospital asthmaadmissions are costly,2 and longer time tophysiologic readiness for discharge (PRD)coincides with increased length of stay andcost.3 Determinants of PRD for asthmaexacerbations are multifactorial, reflectingin part disease heterogeneity, the presenceof comorbid conditions,4 and the rapidity ofresponse to exacerbation therapies.5–7 Inaddition to patient-level factors, the systemsin which care occurs have the potential toinfluence PRD timing. System-level carepractices may dictate the timing or durationof therapies, the use of diagnostic testing,preferred methods of medicationadministration, patient monitoringpractices, discharge criteria, and otheraspects of acute exacerbation care. System-level practices in asthma, particularlywith regard to treatment standardization,guideline implementation,8 and albuterolweaning protocols,9 are associated withpatient outcomes. However, there is a needfor multisite studies in which researchersaddress the distinct and combined impactof patient-level risks and system-level carepractices on PRD in acute asthma.

Our goal in this study was to investigatepatient-level risks and system-levelpractices as they relate to PRD for asthmaexacerbations using a unique, multicenter,statewide database called the Ohio PediatricAsthma Repository (OPAR).10 OPAR is acomprehensive, statewide, prospectivestudy in which researchers link clinical,demographic, environmental, and healthoutcomes data from the 6 major children’shospitals in Ohio. By using OPAR, we areuniquely positioned to address howvariability in patient- and system-levelfactors at each site impact PRD duringacute asthma exacerbation.

METHODSSubject Identification and Eligibility

OPAR was initiated and funded by the stateof Ohio to better understand and optimizeasthma care practices.10 Children aged 2 to17 years who were admitted for asthma,wheezing, or reactive airway disease at 1 of6 Ohio children’s hospitals were eligible.Each participant’s parent or legal guardian

provided informed consent, and assentwas obtained from children .7 years old.For this analysis, participants recruitedbetween December 2012 and September2013 were included. As previouslyreported, the mean proportion of eligibleparticipants enrolled was 68% (53%–81%).Nonparticipants did not differ fromparticipants by age or sex.10 This study wasapproved by the Institutional Review Board.

Questionnaires and Clinical DataCollection

Participants completed questionnairesthat were used to capture demographics,symptom history, and health care use forwheezing and/or asthma. Information fromadmission, emergency department (ED)course, and ICU course (includingrespiratory assessment tools used, drugsadministered, and providers) was collectedfrom the medical record.

Outcome Definition: PRD

Medical criteria for PRD varied. Fourhospitals used albuterol spacing every4 hours (q4h), and 2 hospitals usedalbuterol spacing every 6 hours.10 Toaccount for these differences, we definedPRD as the first time point at which thepatient demonstrated sufficient clinicalimprovement while receiving albuterolinhalation treatments no more frequentlythan q4h. We measured the time frominpatient (IP) or ICU admission until thepatient reached the first 4-hour albuterolspacing (PRDIP) (Fig 1). If a patient wasdischarged before meeting q4h, then PRDIPwas the time from IP admission todischarge. We also measured PRDTOT asthe time from emergency departmentpresentation to first 4-hour albuterolspacing (Fig 1). If a patient was dischargedbefore meeting q4h, then PRDTOT was definedas the time from ED presentation todischarge. Because of skewing, PRDIP andPRDTOT were log-transformed.

Covariate Definitions

Chronic Severity and Risk

Chronic asthma severity classification wasassigned as intermittent, mild persistent,moderate persistent, or severe persistenton the basis of baseline symptomfrequencies according to Expert Panel

Report 3.11 High risk for asthmareadmission was defined as parental reportof hospitalization for asthma in the past12 months. We combined asthma severityand risk into 4 categories: intermittent, mildand low risk; moderate, severe and low risk;intermittent, mild and high risk; andmoderate, severe and high risk.10

Nonstandard Care Practices

We defined nonstandard care practices asintravenous (IV) steroid use, IP ipratropiumadministration, ICU admission, chestradiograph, continuous albuterol, andantibiotic administration.

Statistical Analyses

Our primary goal was to identify factorsassociated with PRD. Because demographicsand care practices varied across hospitals,10

analyses were performed with mixed linearmodels in which hospital was includedas a random effect. Because the factorsassociated with PRD may be correlated,we used a multistep strategy. First, wedetermined the relationships between PRDIPand each factor individually. These analysesreveal information about individual-levelassociations; however, they do not accountfor correlation between variables. Therefore,we next generated a multivariate model,considering variables exhibiting a marginallevel of significance (P , .2) in the individualscreens. Variables that were significant in theindividual but not the multivariable analyseswere evaluated for collinearity by usingcontingency tables. When collinearity existed,only 1 variable was included. The finalmultivariable model eliminated variables atP. .2. We used a similar strategy to evaluatefactors associated with PRDTOT but alsoevaluated ED practices. For antibiotic use,steroid administration route, and chestradiograph, we created combined variableswith 4 categories (ED only, IP only, both, andnone), which replaced the dichotomousvariables. Because ED dexamethasone wasused primarily at a single hospital, analysesusing only that hospital were evaluated.Additionally, we modeled PRDIP in the EDsubpopulation to ensure consistency ofresults (data not shown).

To determine if hospital differences persistedafter accounting for demographics,

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nonstandard care practices, and hospitalpractices, we performed multivariatemodeling for hospital association. Weincluded a fixed and a random effect forthe number of nonstandard care practicesreceived. We included demographic andIP practices that were significant in themultivariable PRDIP model as covariates.We generated a second multivariable PRDIPmodel that incorporated ED practices andlocation-dependent practices as covariates.These models allowed for the comparison ofPRD among hospitals. Statistical analyseswere performed by using SAS 9.4 (SASInstitute, Inc, Cary, NC).

RESULTSCharacteristics of the StudyPopulation

The study population included 1005 childrenwho were primarily boys, African American,and on public insurance (Fig 1). Because notall enrollees presented to an OPAR hospital-affiliated ED (direct admit), analyses ofPRDIP include fewer children (n 5 865;Fig 1). PRDIP and PRDTOT, as well as the

proportion of patients who receivednonstandard care practices, variedmarkedly among hospitals (Table 1).

Factors Influencing PRDIP

In the individual screen, adolescent age,injected steroid route, oral steroids,ipratropium, ICU admission, chestradiograph, continuous albuterol, antibiotics,specialist overseeing physician, continuouspulse oximetry, and albuterol weaning bymultiple providers were associated withincreased PRDIP (Supplemental Table 2).

Because factors associated with PRDIP maycorrelate, we considered factors jointly.Demographics contributed to increasedPRDIP after accounting for nonstandard careand routine care practices. There was a2-hour increase in PRDIP for children withpublic compared with private insurance(P 5 .02) and a 2.7-hour increase foradolescents (aged 13–17 years) comparedwith younger children (P 5 .04; Fig 2).

Nonstandard care practices were alsoassociated with PRDIP in the multivariable

model (Fig 2). The receipt of continuousalbuterol increased PRDIP by almost 4 hours(P , .001). Children receiving injectedsteroids had a 9.7-hour longer PRDIP thanthose who only received oral steroids(P , .001). Receiving azithromycinincreased PRDIP by 5.9 hours (P , .001). Theadministration of ipratropium and receipt ofa chest radiograph increased PRDIP by5.6 and 4.3 hours, respectively (P , .001 forboth). ICU admission was not associatedwith PRDIP (P 5 .82) because of its highcorrelation with continuous albuterol(Spearman’s r 5 0.80; P , .0001). Theseresults support that nonstandard carepractice use is associated with PRDIP.

IP care practices also contributed to PRDIPin the multivariable model (Fig 2). Childrenreceiving continuous pulse oximetry, aloneor in combination with spot checks, had a3- to 3.5-hour longer PRDIP than childrenreceiving only spot checks (P , .05).Other than the small number of childrendischarged from the ICU, the providerperforming weaning assessments did not

FIGURE 1 Subject identification and PRD definitions.

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markedly alter PRDIP. PRDIP was notassociated with the managing physician(P 5 .08; Fig 2); however, children who wereseen only by a generalist were less likelyto receive nonstandard care practices(odds ratio 5 0.20; confidence interval 50.15–0.26; P, .0001; data not shown). Theseresults reveal that continuous pulseoximetry is associated with longer PRDIPafter accounting for other factors.

Factors Influencing PRDTOT

ED-specific and location-dependent factors(performed in the ED, IP, or both) that wereindividually associated with increasedPRDTOT included injected steroids outsidethe ED, not receiving ED dexamethasone,receiving ED magnesium sulfate, chestradiograph not performed in the ED, andthe administration of IP and antibioticsoutside of the ED (Supplemental Table 3).Because dexamethasone was used mainlyat the Cleveland hospital, we testedthe association between PRDTOT anddexamethasone for Cleveland and foundthat it was strongly associated withshorter PRDTOT (P , .001; data notshown).

In the multivariable model, location-dependent practices were associated withPRDTOT (Fig 3). Receiving antibiotics only in

IP was associated (P # .001) with a 6- to6.7-hour longer PRDTOT than receivingantibiotics in the ED and IP, ED only, and notreceiving antibiotics. Furthermore, havingchest radiographs in the IP only or in boththe IP and ED was associated with 5.6- and7.9-hour longer PRDTOT, respectively, than nothaving a chest radiograph (P , .001).Individuals receiving a chest radiographonly in the ED did not have a significantlyincreased PRDTOT (P 5 .06). Receiving IVsteroids only in IP was associated with8.4- and 7.1-hour longer PRDTOT thanreceiving no IV steroids or only in the ED,respectively (P , .001).

Dexamethasone and magnesiumadministration in the ED were marginallysignificant in the multivariate model (P #

.14), although they were highly significantindividually (Supplemental Table 3).Individuals receiving magnesium sulfatewere more likely to receive nonstandard care(odds ratio 5 5.53; confidence interval 53.87–8.05; P , .001; data not shown). Toevaluate the effect of dexamethasone onPRDTOT, we restricted the analyses toCleveland. Those receiving dexamethasonewere less likely to receive nonstandard care(60.2% vs 87.9%; P 5 .0041; data notshown), be admitted to the ICU (36.0% vs69.7%; P , .0001), and to receive injected

steroids (31.8% vs 72.7%; P , .0001). In amultivariate model that was not adjustedfor nonstandard care, those receivingdexamethasone stayed for 11.7 hoursless (P 5 .007; data not shown) than thosewho did not.

Variation in PRDIP Among Hospitalsis Due in Part to Variation in Hospital-Level Factors

After accounting for demographics,nonstandard care, and IP practices ordemographics, nonstandard care, IPpractices, and ED practices, the differencesin PRD among the hospitals substantiallydecreased compared with what was seenin the unadjusted model (Fig 4). In theadjusted models, the longer PRDIP at theCleveland site observed in the unadjustedmodel decreased. Thus, hospital-levelfactors contributed substantially to PRDIP.It is important to note that even afteradjustment for system-level variation,differences in PRDIP among the sitespersisted, suggesting that other,unaccounted factors play a role.

Opportunities for ProcessImprovement by Site

To determine if there are opportunities forimprovement within each hospital, weevaluated hospital practices that were

TABLE 1 Prevalence of IP and ED Practices Associated With Shorter Time to PRD by Hospital

Dayton Akron Cincinnati Toledo Cleveland Columbus

n , IP (ED) 115 (114) 103 (72) 365 (356) 58 (35) 196 (121) 168 (168)

PRDIP, mean 6 SD 9.74 6 0.06 18.06 6 0.07 19.13 6 0.04 22.46 6 0.09 33.57 6 0.05 38.66 6 0.05

PRDTOT, mean 6 SD 13.77 6 0.05 20.77 6 0.07 24.71 6 0.03 26.09 6 0.10 39.01 6 0.05 44.60 6 0.04

Receipt of nonstandard care, % 20.0 68.0 45.2 70.7 93.1 63.1

Intervention

Pulse oximetry, % spot only (n) 77.4 (89) 72.8 (75) 8.8 (32) 67.3 (39) 39.3 (77) 4.8 (8)

ED dexamethasone % (n in ED) 0 (0) 1.4 (1) 0.2 (1) 0 (0) 72.7 (88) 0.6 (1)

ED antibioticsa % (n in ED) 6.1 (7) 13.8 (10) 3.9 (14) 11.4 (4) 9.1 (11) 8.3 (14)

ED chest radiographb % (n in ED) 56.1 (64) 44.4 (32) 47.2 (168) 45.7 (16) 51.2 (62) 43.3 (73)

ED IV steroidsa % (n in ED) 13.2 (15) 37.5 (27) 11.5 (41) 14.3 (5) 12.4 (15) 31.5 (53)

ED intervention among those receiving intervention

Antibioticsa, % (n in ED/n ever) 38.9 (7/18) 47.6 (10/21) 30.4 (14/46) 26.7 (4/15) 28.2 (11/39) 30.4 (14/46)

Chest radiographb , % (n in ED/n ever) 90.1 (64/71) 69.6 (32/46) 78.1 (168/215) 55.1 (16/29) 63.3 (62/98) 69.5 (73/105)

IV steroidsc, % (n in ED/n ED and IP) 77.8 (7/9) 64.7 (11/17) 18.1 (17/94) 12.5 (1/8) 8.9 (4/45) 28.1 (9/32)

a Initiated in ED.b Received only in ED.c Includes individuals who received during IP hospital course but excludes individuals receiving in both the ED and IP.

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associated with shorter PRDIP by hospital(Table 1). The use of spot-only pulseoximetry monitoring was .72% at Daytonand Akron, but it is rarely exclusivelyperformed in Cincinnati or Columbus.Dayton and Akron also had higher rates of

the initiation of antibiotics and IV steroids inthe ED compared with the other sites. EDdexamethasone use was limited almostexclusively to the Cleveland site but wasassociated with a significantly shorter PRDIPwhen that site was evaluated alone.

DISCUSSION

When children are admitted for an acuteasthma exacerbation, the goal is to useguideline-level care to bring the patientto PRD in the shortest amount of time.However, treatment guidelines for IP asthma

FIGURE 2 Demographic, severity indicator practices, and IP practices are associated with PRDIP in a multivariable model. LSM, least square mean;RT, respiratory therapist. * P , .05; ** P , .01; *** P , .001.

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exacerbation translate into practicedifferently, leading to wide variation inhospitals. In this article, using a prospectivestudy of 6 major hospitals in Ohio (OPAR),we demonstrate that PRD timing ismultifactorial and includes a substantialcontribution from hospital-level factors.Although clearly influenced by patientfactors, the differences in hospital practicesidentified herein may offer an opportunityfor improvement. Specifically, our resultsreveal that when clinically indicated, usingspot-only pulse oximetry may shorten timeto PRD. Furthermore, because those who didnot receive nonstandard care had markedlylower PRD, minimizing the use of

nonstandard care practices unlessmedically warranted is critical. Theseresults reveal that the use of standardizedand evidence-based severity assessments toidentify those who warrant nonstandardcare is essential.

We found that continuous pulse oximetryuse was associated with increased time toPRD. It has been recommended to limitcontinuous pulse oximetry in children withsevere illness, who likely need intensivemonitoring (eg, in the ICU), but those withmild and moderate respiratory diseasecan be managed with spot checks.12

Furthermore, although pulse oximetryoffers a noninvasive method for measuring

arterial oxygen saturation, a majorlimitation is that of motion artifacts.13

Continuous monitoring likely increasesthe observation of artifacts and othernonclinically significant, transient decreasesin oxygen saturation that may lead to moreaggressive care and increase time to PRD.In several of the OPAR hospitals, the use ofcontinuous pulse oximetry is routine. Ourresults suggest that limiting the use ofcontinuous pulse oximetry to only when it isclinically indicated may decrease time toPRD. Additional studies are required toverify this finding.

We also found that nonstandard carepractice use is associated with increased

FIGURE 3 ED practices and time-dependent practices associated with PRDTOT in a multivariate model. LSM, xxx. * P , .05; ** P , .01; *** P , .001.

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PRD. One reason for nonstandard carepractices use is the more severe or complexexacerbation. Previous researchers havefound comorbid respiratory infections14,15

and respiratory failure16 to be associatedwith increased length of stay. In addition,the use of nonstandard care practices thatcontribute to delaying PRD may be relatedto physician preference or a lack of use ofevidence-based practices across providers.Interestingly, in our previous article,10 wenoted a high rate of IP ipratropium use atthe Cleveland hospital. It was determined

that this high rate had no relation toexacerbation, but rather it was due to astandard order set. The routine use ofipratropium on the IP units in Cleveland hassince been discontinued, but our data revealthe need to minimize nonstandard careunless it is medically warranted.

Notably, dexamethasone use in the EDwas associated with shorter time to PRD.Previous studies have revealed potentialbenefits of dexamethasone, includingdecreased vomiting and improvedadherence.17 Furthermore, dexamethasone

has been associated with shorter length ofstay and comparable readmission rates.18

We found that individuals receiving EDdexamethasone were less likely to beadmitted to the ICU or receive IV steroids,suggesting that receiving ED dexamethasonemay circumvent the need for moreaggressive IP interventions. Because thisfinding was driven by nearly exclusive use inCleveland, it requires confirmation. Early(within 1 hour of arrival) administration ofsystemic corticosteroid in the ED has beenassociated with fewer admissions and

FIGURE 4 Variation in timing to PRD by hospital is partially explained by demographics, exacerbation severity, and IP and ED practices. * P , .05;** P , .01; *** P , .001.

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shorter length of stay.19 Although the earlyadministration of dexamethasone in theCleveland ED could be an alternativeexplanation for the differential outcome,this was not the practice at this site. As partof process improvement, an evaluation ofthe use of dexamethasone in the ED hasbeen implemented at Cincinnati on the basisof our findings, and data on readmissionand hospital PRD are being prospectivelycollected.

The timing of certain care practices (chestradiographs, antibiotics, and/or IV steroidsin the ED rather than IP) was alsoassociated with shorter PRD timing amongthose who received the practice. There are2 possible reasons for such an association.First, an earlier initiation of clinicallyimportant and indicated specific treatmentsmay shorten PRD. When indicated bysymptoms or physical findings (eg, fever,localized adventitious lung sounds,hypoxemia, or vomiting), initiating suchinterventions in the ED may shorten lengthof stay by 6 to 10 hours.19,20 If this is thecase, then there could be opportunities forimprovement by incorporating evidence-based care algorithms in the ED, giventhe marked variations among the OPARhospitals. Indeed, the use of validatedassessment tools or development of moresensitive scores could expedite theidentification of children with more severeillnesses who would benefit from an earlierinitiation of treatments. It is also possiblethat nonstandard interventions may be usedmore indiscriminately in the ED on patientswith milder exacerbations, and then these

care practices are discontinued duringthe IP stay. However, we are unable todetermine if certain nonstandard carepractices, such as chest radiographs orantibiotics, were definitely indicated. Clearly,additional studies are warranted todetermine guidelines for ED physicians;however, the routine use of such practicesshould be discouraged because childrenwho do not require nonstandard care haveshorter PRD.

Not surprisingly, patient-level factors, suchas public insurance, were also associatedwith increased time to PRD. Our finding isconsistent with previous studies in whichresearchers have found that children withpublic insurance had longer length of stay21

and higher hospital charges.22 This may bebecause socioeconomic status (for whichinsurance is a proxy) is considered arough marker of environmental and/orbehavioral exposures that may contributeto exacerbation severity.23 Indeed, oncematched for severity, researchers in amultisite study failed to find differences inlength of stay by insurance.24

A major limitation of our study is that the6 OPAR hospitals do not use consistentmeasures to evaluate exacerbation severity,such as the use of an established scoringsystem.25–27 This is a critical gap in currentpractice and makes multisite qualityimprovement challenging. Although thenonstandard care practices that weexamined herein may be indicators of amore severe course (confounding byindication), they are not exacerbation

severity measures and cannot be usedas such. Furthermore, it is important torecognize that simply shortening PRD maynot result in optimal patient outcomes.Patients who fail standard ED therapy andthen also fail to respond to or deterioratewith standard IP treatment will also requirenonstandard care practices and longer timeto PRD. It is important to note that evenafter adjustment for hospital-level practicevariation, significant differences in PRDamong the sites persisted, suggesting thatother, unaccounted factors play a role. Thissuggests that factors such as adherenceand underlying differences in diseasebiology (eg, treatment response phenotypes,immunologic phenotypes, and geneticvariation) may also contribute.

CONCLUSIONS

Variation in care practices exists within andamong children’s hospital systems in Ohio,and specific, system-level factors andtherapies contribute to PRD. We foundseveral modifiable factors that warrantfurther investigation. Furthermore, theassessment of exacerbation severity iscritical to ensure that those who requirenonstandard care receive it in a timelymanner while minimizing nonessential carefor those who are not likely to need it.

Acknowledgments

We thank the staff at each of theparticipating sites who helped recruitthe patients for this study as well as theparticipants and their families.

Dr Simmons contributed to the conception and design of the study, interpreted results, and drafted the manuscript; Dr Biagini Myers contributed to subjectrecruitment and acquisition of data and the study design, interpreted results, and drafted the manuscript; Dr Martin contributed to the study design, oversaw,performed, and interpreted data analyses, and drafted the manuscript; Dr Kercsmar contributed to the conception and design of the study and data acquisitionand interpreted results; Dr Schuler interpreted results and drafted the manuscript; Dr Pilipenko and Ms He performed data analyses and interpreted results;Mr Austin and Mr Kroner designed data collection instruments and supervised subject recruitment, data acquisition, and data management; Dr Nguyeninterpreted results; Drs Ross, McCoy, Alter, Gunkelman, and Vauthy contributed to the conception and design of the study and oversaw subject recruitment;Dr Khurana Hershey conceived the Ohio Pediatric Asthma Repository, oversaw its design, implementation, and data acquisition, and interpreted results; and allauthors reviewed and revised the manuscript and approved the final manuscript as submitted.

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