Exercise-Induced Wheeze, Urgent Medical Visits, andNeighborhood Asthma Prevalence

WHAT’S KNOWN ON THIS SUBJECT: The prevalence of asthma andassociated urgent medical visits vary dramatically acrossneighborhoods in New York City. Some, but not all, children withasthma wheeze when they exercise.

WHAT THIS STUDY ADDS: Exercise-induced wheeze was morecommon for asthmatic children living in neighborhoods withhigher versus lower asthma prevalence. Because exercise-induced symptoms indicate a propensity for rapid-onsetsymptoms, this increased prevalence may contribute to theobserved increase in urgent medical visits.

abstractOBJECTIVE: Exercise-induced wheeze (EIW) may identify a distinctpopulation among asthmatics and give insight into asthma morbidityetiology. The prevalence of pediatric asthma and associated urgentmedical visits varies greatly by neighborhood in New York City and ishighest in low-income neighborhoods. Although increased asthmaseverity might contribute to the disparities in urgent medical visits,when controlling for health insurance coverage, we previously ob-served no differences in clinical measures of severity between asth-matic children living in neighborhoods with lower (3%–9%) versushigher (11%–19%) asthma prevalence. Among these asthmatics, wehypothesized that EIW would be associated with urgent medical visitsand a child’s neighborhood asthma prevalence.

METHODS: Families of 7- to 8-year-old children were recruited intoa case-control study of asthma through an employer-based health insur-ance provider. Among the asthmatics (n = 195), prevalence ratios (PRs)for EIW were estimated. Final models included children with valid meas-ures of lung function, seroatopy, and waist circumference (n = 140).

RESULTS: EIW was associated with urgent medical visits for asthma(PR, 2.29; P = .021), independent of frequent wheeze symptoms. Incontrast to frequent wheeze, EIW was not associated with seroatopyor exhaled NO, suggesting a distinct mechanism. EIW prevalenceamong asthmatics increased with increasing neighborhood asthmaprevalence (PR, 1.09; P = .012), after adjustment for race, ethnicity,maternal asthma, environmental tobacco smoke, household income,and neighborhood income.

CONCLUSIONS: EIW may contribute to the disparities in urgent medicalvisits for asthma between high- and low-income neighborhoods.Physicians caring for asthmatics should consider EIW an indicatorof risk for urgent medical visits. Pediatrics 2013;131:e127–e135

AUTHORS: Timothy R. Mainardi, MD, MA,a Robert B.Mellins, MD,b Rachel L. Miller, MD,a,b,c Luis M. Acosta, MD,c

Alexandra Cornell, MD,d Lori Hoepner, MPH,c,e James W.Quinn, MA,f Beizhan Yan, PhD,g Steven N. Chillrud, PhD,g

Omar E. Olmedo, BS,c Frederica P. Perera, DrPH,c Inge F.Goldstein, DrPH,h Andrew G. Rundle, DrPH,h Judith S.Jacobson, DrPH,h and Matthew S. Perzanowski, PhDc

aDivision of Pulmonary, Allergy, Critical Care Medicine,Department of Medicine, and bDepartment of Pediatrics,Columbia University College of Physicians and Surgeons, NewYork, New York; cDepartments of Environmental Health Sciences,hEpidemiology, and eData Coordinating Center, Mailman School ofPublic Health, Columbia University, New York, New York; fInstitutefor Social and Economic Research and Policy, ColumbiaUniversity, New York, New York; dDivision of PediatricPulmonology, Dartmouth-Hitchcock Medical Center, Lebanon, NewHampshire; and gLamont-Doherty Earth Observatory, ColumbiaUniversity, Palisades, New York

KEY WORDSasthma, allergy, exercise, emergency department, exercise-induced bronchoconstriction

ABBREVIATIONSBC—black carbonED—emergency departmentEIB—exercise-induced bronchoconstrictionEIW—exercise-induced wheezeETS—environmental tobacco smokeFeNO—fractional exhaled nitric oxideFEV1—forced expiratory volume in 1 secondFVC—forced vital capacityGEE—generalized estimating equationGIS—geographic information systemHAPN—higher asthma prevalence neighborhoodIgE—immunoglobulin EISAAC—International Study of Asthma and Allergy in ChildhoodLAPN—lower asthma prevalence neighborhoodNO—nitric oxidePR—prevalence ratioSES—socioeconomic statusUHF—United Hospital Fund

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Patterns of asthma symptoms are im-portant to understanding the etiologyand treatment of the disease.1,2

Exercise-induced bronchoconstriction(EIB) and exercise-induced wheeze(EIW) are common among asthmatics,with estimates that 40% to 90% ofasthmatics have symptoms with exer-cise.3 With EIB, drying and cooling of themucosa after brief exercise causerapid bronchoconstriction through re-lease of inflammatory mediators in-cluding histamine and leukotrienes.4,5

Although different entities, EIB maycause the symptoms that occur withEIW for many asthmatics. Although EIWis often described as a phenotype ofasthma,2,6,7 it may be simply a discreteclinical expression of asthma.8 EIWamong mild asthmatics has been im-plicated in.40 deaths during sportingactivities between 1993 and 2000.9

Therefore, EIW may represent a clini-cally relevant asthma phenotype de-fined by a rapid onset of symptoms.

In New York City, the range in pediatricasthma prevalence (3%–19%) amongneighborhoods is striking.10 The fre-quency of associated urgent medicalvisits varies even more dramatically;emergency department (ED) visits forasthma are up to 20 times more com-mon in lower than in higher socioeco-nomic status (SES) neighborhoods.10,11

Differences in asthma severity couldexplain these differences in urgentmedical visits. However, after control-ling for health insurance coverageamong a middle-income population of7- to 8-year-old asthmatics, we ob-served no difference in clinical indica-tors of asthma severity (lung function,exhaled nitric oxide [NO], and fre-quency of wheeze) between childrenliving in higher versus lower asthmaprevalence neighborhoods (LAPNs).12,13

Although neighborhood SES was asso-ciated with urgent medical visits,13 weconsidered the possibility that anunderlying biological determinant of

these differences might also be in-volved. An asthma phenotype associ-ated with rapid-onset exacerbations,like EIW, might increase a child’s riskfor an urgent medical visit for asthma.We hypothesized that EIW would beassociated with urgent medical visits,independent of clinical indicators ofasthma severity, and with the preva-lence of asthma in a child’s neighbor-hood. To minimize heterogeneity inpotential confounders such as accessto health care and household income,we tested this hypothesis among thechildren described previously,12–14

a group of middle-income asthmaticchildren living throughout New YorkCity neighborhoods.

METHODS

The NYC Neighborhood Asthma and Al-lergy Study is a case-control study ofchildren with and without asthma de-scribed previously.12–14 Parents of 7- to8-year-old children were recruitedthrough the Health Insurance Plan ofNew York, a provider used primarily bya middle-income population. Neigh-borhoods were selected based onUnited Hospital Fund (UHF) level (sev-eral zip codes) asthma prevalenceamong 5-year-olds as reported by theNew York City Department of Healthand Mental Hygiene.10 All LAPNs (3%–9%) and higher asthma prevalenceneighborhoods (HAPNs; 11%–19%) inthe Bronx, Brooklyn, Queens, andManhattan were selected for re-cruitment by mail.

A caregiver completed a detailedquestionnaire on the child’s health, thefamily’s demographics, and environ-mental tobacco smoke (ETS) exposure.Parents were questioned about howmany hours per week their child ex-ercised or played sports. During thehome visit, spirometry, fractional ex-haled NO (FeNO) testing, and waistcircumference measurements wereconducted, serum was collected for

total and allergen specific immuno-globulin E (IgE), and settled dust andairborne particulate matter were col-lected (details, online supplement).Columbia University’s Institutional Re-view Board approved this study.

Asthma Case Definition,Exercise-Induced Wheeze, andFrequent Wheeze

Asthma cases were defined by ques-tionnaire, including the modules fromthe International Study of Asthma andAllergy in Childhood (ISAAC). Childrenwere classified as asthmatic if theircaregiver reported at least 1 of thefollowing for the child in the past 12months: (1) wheeze, (2) being awak-ened at night by cough without havinga cold, (3) wheeze with exercise, or (4)report of medication use for asthma.Children not meeting the asthma defi-nition were excluded from the currentanalyses.

The following outcomes also werereported for the previous 12 months.Exercise-induced wheeze (EIW) wasdefined as an affirmative response toquestions about (1) wheezing afterrunning or active play and/or (2) child’schest sounding wheezy during or afterexercise. Frequent wheeze was definedas $4 episodes of wheeze. Urgentmedical visits were defined as a posi-tive response to questions about takingthe child either to the doctor in a hurryor to the ED due to breathing difficul-ties.

Neighborhood Variables

Children’s home addresses were geo-coded and linked to a geographic in-formation system (GIS) demographicdatabase described previously.12,15 Achild’s local neighborhood wasassigned the demographic character-istics of households in the 500-m ra-dius surrounding the home. Additionalbuilt environment variables related toair pollution sources are described in

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the online supplement. Each child wasassigned a neighborhood asthmaprevalence based on the UHF levelasthma prevalence described earlier.10

Statistical Analysis

FeNO and total IgE were log-normallydistributed; we used natural log-transformed values in the analyses.GIS variables were not normally dis-tributed and thus were compared byusing nonparametric tests. Prevalenceratios (PRs) were calculated by usinggeneralized estimating equation (GEE)models with UHF used as a clustervariable because the neighborhoodasthma prevalence was available at theUHF level. Variables conventionallyconsidered as potential confounderswere included in the multivariablemodels including gender, race, His-panic ethnicity, maternal asthma, ETS,neighborhood income, and materialhardship.16 Sensitivity analyses of theassociation between neighborhoodasthma prevalence and EIW are de-scribed in the online supplement. Datawere analyzed in SPSS version 17(SPSS, Inc, Chicago, IL) and visualized inR version 2.14.0.

RESULTS

There were 195 children classified asasthmatic who had a blood sample, 95and 100 in LAPN and HAPN, respectively(Fig 1). Among those, valid lung func-tion and FeNO were available on 166(eg, 85%) and 167 (86%) children, re-spectively. Waist circumference wasnot measured in the first 25 childrenand was thus available on 170 (87%)children. A complete set of data formultivariable models including lungfunction, household income, and waistcircumference was available on 140children.

Asthmatics in the LAPN and HAPN hadsimilar demographics, except for dif-ferences in Asian and mixed races,Hispanic ethnicity, report of seeing

cockroaches or mice, and the presenceof a smoker in their home (Table 1). Asreported previously, there were nodifferences in clinical measures ofasthma severity (lung function, FeNO,symptom frequency) or seroatopy(measureable IgE to at least 1 inhalantallergen) between asthmatics in theLAPN versus HAPN (Table 1).13 The localneighborhoods (500 m surroundingthe homes) differed in the proportionsof households reporting African-American race and Hispanic ethnicityand median household income.

Wheeze, Urgent Medical Visits, andMedication Use

Among the children classified as asth-matic, 84/195 (43%) had a report of EIW,whereas frequent wheeze was lesscommon (21%). Many but not all of thechildren with frequent wheeze also hadEIW, whereas more than half of thosechildren with EIW did not have frequentwheeze (Fig 2). Urgent medical visitsfor asthma in the past year were alsocommon (26.7%) with 21.9% and 17.5%reporting taking their child to a doctorin a hurry and to the ED, respectively. Ina multivariable model controlling forpotential confounders, EIW (PR: 2.29[1.13–4.63]; P = .021) and frequentwheeze (PR: 2.07 [1.12–3.84]; P = .020)

were independently associated (samemodel) with urgent medical visits. In 2similar models, EIW was associatedwith taking their child to the doctor ina hurry (PR: 2.62 [1.19–5.75]; P = .016)and borderline associated with ED vis-its for asthma (PR: 2.31 [0.95–5.63]; P =.066). Many asthmatics with EIW hadused controller medications in the pastyear (42%) and a majority, but not all,had used short-acting bronchodilators(65%) in the past year. The associationbetween EIW and urgent medical visitsremained statistically significant (PR:2.27 [1.11–4.63]; P = .024) after adjust-ment for use of preventative medi-cations (1%, 16.5%, and 14.4% hadtaken long-actingb antagonist, inhaledor oral corticosteroids and leukotrienemodifiers in the past year, respec-tively).

Comparing Clinical Features of EIWand Frequent Wheeze

To validate EIWasdistinct from frequentwheeze, we examined the clinical fea-tures of these phenomenon, first inbivariate analyses (Fig 3) and then inadjusted models. In multivariableanalyses with individual models foreach clinical variable, after controllingfor gender, race, and Hispanic ethnicity,EIW was associated with forced

FIGURE 1Map of New York City depicting study subjects’ places of residence overlaying neighborhood asthmaprevalence. Neighborhood asthma prevalence was defined for 5-year-old school children as reportedby the New York City Department of Health and Mental Hygiene.10 Participants were recruited fromneighborhoods with lower (3%–9%) or higher (11%–18%) neighborhood asthma prevalence.

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expiratory volume in 1 second/forcedvital capacity FEV1/FVC (as percent)(PR: 0.95 [0.92–0.99]; P = .010), but notwith FeNO (PR: 1.21 [0.89–1.65]; P =.25) or total IgE (PR: 1.06 [0.92–1.22];P = .43). In similar models, frequentwheeze was associated with FEV1/FVC(PR: 0.94 [0.89–0.99]; P = .025), FeNO(PR: 2.21 [1.40–3.49]; P = .001), andtotal IgE (PR: 1.61 [1.29–2.00]; P ,.001). Seroatopy was associated withfrequent wheeze (PR: 3.55 [1.48–8.54];P = .005) but not EIW (PR: 1.12 [0.76–1.92]; P = .41).

Neighborhood Asthma Prevalenceand EIW

The prevalence of EIW increased withincreasing neighborhood asthmaprevalence in bivariate analyses (Fig4A) and after adjustment for potentialconfounders (PR: 1.06 [1.003–1.13]; P =.040) including local neighborhood in-come. The prevalence of frequentwheeze was not associated withneighborhood asthma prevalence inbivariate analyses (Fig 4B) or in themultivariable model (PR: 0.93 [0.83–1.04]; P = .19). As we have described

previously,13 the prevalence of urgentmedical visits modestly increasedwith increasing asthma prevalence,although this was not statistically sig-nificant (Fig 4C). In the multivariablemodel, local neighborhood income (PR:0.96 [0.93–0.998]; P = .039) and notneighborhood asthma prevalence (PR:0.99 [0.90–1.09]; P = .84]) was associ-ated with urgent visits and a similarassociation was observed with ED vis-its as the outcome (data not shown).

Stratification by Seroatopy,Sensitivity Analyses, and Report ofExercise

In multivariable models, neither lungfunction nor neighborhood asthmaprevalence was associated with prev-alence of EIW among the nonseroatopicasthmatics, although waist circumfer-ence trended toward a positive but notstatistically significant association(Table 2). Among seroatopic children,both lung function and neighbor-hood asthma prevalence were in-dependently associated with EIW. Theassociation between neighborhoodasthma prevalence and EIW was notaltered (,10% change in PR) by step-wise inclusion of previously reportedmeasures and estimations of allergensand combustion byproducts in oraround the child’s homes (Supple-mental Table 3). Median reported timespent exercising or playing sports didnot differ significantly (P . .05) be-tween children in HAPN versus LAPN orbetween children with or without EIWor urgent visits (all medians 4–5 hoursper week). Also, the frequency of chil-dren with limited exercise or sports(,1 hour per week) did not differ byneighborhood or report of symptoms(data not shown).

DISCUSSION

Among middle-income asthmatic chil-dren with the same health insuranceprovider, the proportion of asthmatics

TABLE 1 Characteristics of the Study Participants and Their Neighborhood (n = 195)

LAPN HAPN P

Child’s demographicsBoy (%) 59/95 (62.1) 53/100 (53.0) .20African-American race (%)a 43/95 (45.3) 55/100 (55.0) .17Asian race (%)a 16/95 (16.8) 2/100 (2.0) ,.001White race (%)a 17/95 (17.9) 7/100 (7.0) .021Other/mixed race (%)a 15/95 (15.8) 34/100 (34.0) .003Hispanic ethnicity (%)b 24/95 (25.3) 45/100 (45.0) .004Mother’s age (mean years) 38.4 35.3 ,.001Maternal asthma (%) 21/95 (22.1) 27/100 (27.0) .43Material hardship reported (%)c 26/94 (27.4) 29/100 (29.0) .80Mother has college degree (%) 37/94 (39.4) 31/98 (31.6) .26Household income (median)d $50–60K $40–45K .077Smoker in the home (%) 14/94 (14.9) 26/99 (26.3) .051Cockroach sightings not rare (%) 19/95 (20.0) 34/100 (34.0) .028Mouse sightings not rare (%) 6/95 (6.3) 15/100 (15.0) .051

Clinical featuresFrequent wheeze past 12 mo (%) 18/95 (18.9) 22/100 (22.0) .60Controller medication past 12 mo (%) 19/94 (20.2) 31/100 (31.0) .086Bronchodilator past 12 mo (%) 52/94 (55.3) 51/100 (51.0) .55Seroatopy (%)e 58/95 (61.1) 61/100 (61.0) .99Total IgE (IU/mL, GM [95% CI]) 111 [85.2–146] 98.9 [70.2–139] .59FeNO (ppb, GM [95% CI])f 10.4 [8.9–12.1] 10.5 [9.0–12.4] .92FEV1/FVC (median [25% to 75%])g 0.88 0.87 .60Waist circumference (cm, mean [95% CI])h 63.1 [61–65] 61.9 [60–63] .32

Neighborhood demographicsi

African-Americans, median, % 28.8 45.9 .040Hispanic, median, % 14.1 42.8 ,.001Households below federal poverty income, median, % 17.3 37.2 ,.001Median household income (median $ in 1000) 40.4 21.3 ,.001Adult population with high school degree, median, % 18.2 10.1 ,.001

95% CI, 95% confidence interval; GM, geometric mean.a Race was not reported for 4 (4.2%) and 2 (2.0%) of the children in the LAPN and HAPN, respectively.b Whether the child was of Hispanic ethnicity was not reported for 1 (1.1%) and 5 (5.0%) of the children in the LAPN and HAPN,respectively.c Mother reported that in the past 6 mo she and her family could not afford needed food, rent, clothing or medical care, orthat gas/electricity was suspended because of bill nonpayment.30d There were 5 families in each group that did not report household income.e Seroatopy defined as serum IgE . 0.35 kIU to at least 1 of the tested allergens.f Missing data for FeNO on 17 (18%) and 15 (15%) children because of high ambient NO in the home at the time of testing.g Missing data for FEV1/FVC on 18 (19%) and 11 (11%) of children.h Missing data for waist circumference on 15 (16%) and 10 (10%).i Neighborhood variables are defined for each of the study participant based on 2000 US Census data for the households inthe 500 m surrounding the participant’s home.

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with a report of EIW increased withincreasing asthma prevalence in thechild’s neighborhood. These findingswere robust in models adjusting forpotential confounders and indicatorsof asthma severity. EIW and frequentwheeze symptoms were independentlyassociated with urgent medical visits.These findings are intriguing because(1) EIW is an indicator of rapid-onsetexacerbation, (2) there is an excess ofurgent medical visits among asth-matics living in neighborhoods withhigher asthma prevalence, and (3) ur-gent medical visits could be triggeredby any rapid-onset exacerbation.

These results build on our previouslyobserved associations between neigh-borhood income and urgent medicalvisits in this study population thatreinforced the established dogma thaturgent medical visits (eg, to the ED) forasthma in lower-income neighbor-hoods have socio-demographic deter-minants.13 Our findings also supporta novel hypothesis: higher prevalenceof an asthma phenotype, defined byrapid-onset symptoms, could providean underlying biological mechanismfor the higher frequency of urgentmedical visits in HAPNs.

The authors of other studies have ex-amined the associations of specifictriggers with slow- versus rapid-onset

asthma exacerbations. Although viralinfections are thought to trigger a ma-jority of asthma exacerbations in chil-dren,17 upper respiratory infectionshave been associated with slower on-set exacerbations.18 In contrast, aller-gen exposure and exercise have beenassociated with more rapid onset.19 Anexplanation for the rapid onset ofsymptoms with EIW lies in the mecha-nism of airway hyperresponsiveness,with release of bronchoconstrictivemediators from inflammatory cellsupon rewarming and rehydration ofthe airway after exercise.5 A previousstudy in children demonstrated that anexercise challenge can increase sub-sequent airway hyperresponsivenessto allergens.20 Although we did not de-termine whether exercise was thetrigger for the exacerbations leadingto the urgent medical visits, our find-ings combined with those revealingsusceptibility to allergen challenge af-ter exercise20 suggest that a report ofEIW may be an indicator of a rapid-onset phenotype that could be aggra-vated by other extrinsic exposures.

It is likely that the EIW phenotype andsocio-demographicdeterminantscouldact together and lead to urgentmedicalvisits. Repeat ED visits for asthma havebeen associated with families lackingconfidence in the efficacy of asthma

medications and not using criteria indeciding to seek emergency care.21,22

The proportion of children with EIW inthis study who had taken controllermedications in the past year (41%)maybe consistent with current NationalHeart, Lung, and Blood Institute guide-lines, or even high, given their rela-tively mild disease.6 However, one-thirdof children with an EIW episode in thepast year had not used a bronchodila-tor, which is not in keeping withcurrent guidelines. A rapid-onset ex-acerbation combined with a parentincorrectly treating their child’s symp-toms could result in an urgent medicalvisit. Collectively, these findings sug-gest that physicians treating even mildasthmatics should consider EIW asa risk for urgent medical visits andprovide appropriate education andmedication.

The overall goal of the New York CityNeighborhood Asthma and AllergyStudy is to better understand neigh-borhood disparities in asthma preva-lence and morbidity. Allergens andcombustion byproducts are 2 types ofexposures that we and others havehypothesized contribute to these dis-parities.23 In support of these hypoth-eses, we demonstrated the relevanceof both cockroach allergen and air-borne black carbon (BC) to allergy andairway inflammation among the chil-dren in this cohort.12,14 Other studieshave revealed that exercise can modifythe effect of air pollutants, includingBC, on asthma outcomes.24,25 We ex-amined whether allergen or combus-tion byproduct exposures partiallyexplained the association betweenneighborhood and EIW (SupplementalTable 3). Despite testing a comprehen-sive set of both measured and modeledestimations of exposures, we wereunable to show any associations withEIW or that exposures substantiallydiminished the association betweenneighborhood asthma prevalence and

FIGURE 2Venn diagrams depicting overlap in frequent wheeze, EIW, and urgent medical visits for asthma. Therewere89/195 asthmaticswhohadno report of EIW, frequentwheeze, or urgentmedical visits and thus notdepicted in this figure.

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EIW. Future studies into the cause of thehigher prevalence of EIW in HAPNs (eg,environment, stress) could lead toa better understanding of the etiologyof urban asthma.

Despite overlap, EIW appeared to rep-resent a phenotype with clinical out-comes that differed from those offrequent wheeze. Poorer lung functionwasassociatedwithbothoutcomes,but

FeNO and total IgE concentrations, tra-ditional biomarkers of inflammationand atopy, although associated withfrequent wheeze, were not associatedwith EIW. In our study, FeNO and total IgEwere higher among asthma cases ingeneral12 and among those cases withEIW (data not shown), than amongcontrols, as others have observed.26

However, unlike frequent wheeze, FeNO

and total IgE did not differ amongasthmatics with and without EIW.

We did observe modest differences inrisk patterns for EIW among childrenwith and without seroatopy. Among thenonseroatopic asthmatics, there wasan (statistically nonsignificant) asso-ciation between EIW and waist cir-cumference but no association withlung function. This lack of association

FIGURE 3Logistic regression lines for univariate analyses are depicted in black with 95% confidence intervals in gray. P values are for the univariate logistic re-gressions. A, EIW with FEV1/FVC (P, .001); B, frequent wheeze with FEV1/FVC (P = .018); C, EIW with FeNO (P = .21); D, frequent wheeze with FeNO (P, .001); E,EIW with total IgE (P = .22); F, frequent wheeze with total IgE (P = .001). Probability of EIW (A, C, D) and frequent wheeze (B, E, F) with FEV1/FVC (A and B), FeNO(C and D), and total IgE (E and F).

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among this group suggests thatdeconditioningmay explain some of thedyspnea in the nonseroatopic asth-matic children, not EIW, which has beenreported previously to be associatedwith obesity.27 But a recent studydemonstrating associations betweenEIW and leptin and adiponectin in se-rum also lends support to the idea thatEIW may have multiple etiologies.28

Neighborhood asthma prevalence wasonly a statistically significant predictorof EIW among the seroatopic asth-matics; however, whether the riskconferred by living in neighborhoods isreally modified by seroatopy or if therelatively small sample size among thenonseroatopics led to type-2 errorremains to be determined.

This study has several limitations. First,because the recruitment method wasdesigned to reduce heterogeneity inhealth care access and household in-come, our participants are not fullyrepresentative of their neighborhoods.

However, the health plan throughwhichthey were recruited has observedneighborhood differences in physician-diagnosed asthma among its membersthat are consistent geographically withthose observed by the New York CityDepartment of Health. Therefore, thesechildren should be representative ofmiddle-income children with employer-based health insurance. Second, we didnot measure EIB. Although an objectivemeasure of bronchoconstriction wouldhave strengthened the findings, theISAAC question assessing EIW hasbeen shown to be predictive of EIBamong 7-year-olds.27,29 Also, althoughour question about EIW came from theinternationally validated ISAAC ques-tionnaire to allow for comparisonwith the many other studies that haveemployed this questionnaire, we didnot ask about other symptoms ofbronchial hyperreactivity after exer-cise (eg, cough, chest tightness) thatcould manifest in the absence of

wheeze. Therefore, we may haveunderestimated the prevalence ofexercise-associated asthma symptomsamong these children. Third, the cross-sectional design of the study did notallow us to evaluate the temporality ofmedication usage and urgent medicalvisits or the impact of previous con-troller medication use on EIW preva-lence. Fourth, this population-basedstudy included primarily asthmaticswith only a few exacerbations in theprevious year, preventing generaliz-ability to asthmatic populations withmore severe asthma. Finally, neigh-borhood differences in access tophysical activity or limitation in phys-ical activity because of previous ex-acerbations could have confoundedour findings. However, we did notobserve differences in the report ofexercise by neighborhood or EIWsymptoms, and the density of parksaround the child’s home was not as-sociated with EIW.

CONCLUSIONS

In a relatively homogenous, middle-income pediatric asthmatic popula-tion, EIW was more commonly reportedfor children living in New York Cityneighborhoods with higher versuslower asthma prevalence. EIW wassignificantly associated with urgentmedical visits among these children,independent of measures of asthma

FIGURE 4Logistic regression lines for the univariate analyses in black with 95% confidence in gray. P values are for the univariate logistic regression. A, EIW (P = .011);B, frequent wheeze (P = .054); C, urgent medical visit (P = .098).

TABLE 2 Multivariable PRs for EIW

Overalla (n = 140)b Nonatopic (n = 52) Atopic (n = 88)

FEV1/FVC 0.96 (0.92–0.997); P = .037 1.02 (0.92–1.13); P = .75 0.94 (0.89–0.99); P = .022Abdominal

circumference1.01 (0.98–1.04); P = .40 1.05 (0.99–1.12); P = .11 1.01 (0.97–1.04); P = .67

Neighborhoodasthma prevalence

1.09 (1.02–1.16); P = .012 1.09 (0.93–1.28); P = .27 1.09 (1.01–1.17); P = .024

a PRs calculated by using a GEE model with community district used as a cluster variable, adjusted for gender, race, Hispanicethnicity, maternal asthma, ETS, neighborhood income, and material hardship.b Sample size restricted based on complete information from cases.

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severity or neighborhood income. Be-cause exercise-induced symptoms in-dicate a propensity for rapid-onsetexacerbation, the increased preva-lence of EIW may be contributing to theobserved increase in urgent medicalvisits. Therefore, the presence of EIWmay be useful to pediatric practi-tioners to identify children at riskfor urgent medical visits. Practition-ers then may apply appropriate

interventions, such as a primary careasthma evaluation, comprehensiveasthma education, and medical treat-ment (eg, bronchodilators and leuko-triene modifiers used before exercise,and/or other medications to improveasthma control).

ACKNOWLEDGMENTSThisprojectwouldnothavebeenpossiblewithout our collaborators at the Health

Insurance Plan of New York; BeatrizJaramillo, DrPH, was instrumental inthe design and initial implementationof the study, and Michael Byrne, MA,has ensured the continued successof the recruitment for the study. Wethank the New York City Neighbor-hood Asthma and Allergy Study fieldteam for their hard work. We thankthe families who have participatedin the study.

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2. Lötvall J, Akdis CA, Bacharier LB, et al.Asthma endotypes: a new approach toclassification of disease entities within theasthma syndrome. J Allergy Clin Immunol.2011;127(2):355–360

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Dr Mainardi contributed to the acquisition, analyses and interpretation of data, and was involved in drafting, revising, and final approval of the article; Dr Mellinscontributed to the conception and design of the study, analyses and interpretation of data, and was involved in revising and final approval of the article; Dr Millercontributed to the conception and design of the study, analyses and interpretation of data, and was involved in revising and final approval of the article; Dr Acostacontributed to the acquisition, analyses and interpretation of data, and was involved in drafting, revising, and final approval of the article; Dr Cornell contributed tothe interpretation of data and was involved in revising and final approval of the article; Dr Hoepner contributed to the acquisition, analyses and interpretation ofdata, and was involved in revising and final approval of the article; Dr Perera contributed to the conception and design of the study and was involved in revisingand final approval of the article; Mr Quinn contributed to the acquisition, analyses and interpretation of data, and was involved in revising and final approval ofthe article; Dr Yan contributed to the acquisition, analyses and interpretation of data, and was involved in revising and final approval of the article; Dr Chillrudcontributed to the conception and design of the study and was involved in revising and final approval of the article; Mr Olmedo contributed to the acquisition ofdata and was involved in revising and final approval of the article; Dr Goldstein contributed to the conception and design of the study, analyses and interpretationof data, and was involved in revising and final approval of the article; Dr Rundle contributed to the conception and design of the study, analyses and interpretationof data, and was involved in revising and final approval of the article; Dr Jacobson contributed to the conception and design of the study, analyses and inter-pretation of data, and was involved in revising and final approval of the article; and Dr Perzanowski contributed to the conception and design of the study, analysesand interpretation of data, and was involved in drafting, revising, and final approval of the article.

www.pediatrics.org/cgi/doi/10.1542/peds.2012-1072

doi:10.1542/peds.2012-1072

Accepted for publication Sep 11, 2012

Address correspondence to Matthew S. Perzanowski, PhD, Department of Environmental Health Sciences, 722 W 168th St, 11th Floor, New York, New York 10032.E-mail: mp2217@columbia.edu

PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).

Copyright © 2013 by the American Academy of Pediatrics

FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.

FUNDING: Supported by the National Institute of Environmental Health Sciences (grant numbers R01 ES014400 and P30 ES09089), Housing and Urban DevelopmentHealthy Homes and Lead Technical Study (HUD NYHHU0003-11). Funded by the National Institutes of Health (NIH).

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Jacobson and Matthew S. PerzanowskiS.Omar E. Olmedo, Frederica P. Perera, Inge F. Goldstein, Andrew G. Rundle, Judith

Chillrud,Alexandra Cornell, Lori Hoepner, James W. Quinn, Beizhan Yan, Steven N. Timothy R. Mainardi, Robert B. Mellins, Rachel L. Miller, Luis M. Acosta,

PrevalenceExercise-Induced Wheeze, Urgent Medical Visits, and Neighborhood Asthma

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Chillrud,Alexandra Cornell, Lori Hoepner, James W. Quinn, Beizhan Yan, Steven N. Timothy R. Mainardi, Robert B. Mellins, Rachel L. Miller, Luis M. Acosta,

PrevalenceExercise-Induced Wheeze, Urgent Medical Visits, and Neighborhood Asthma

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