Journal of Asthma, 48:797–803, 2011Copyright © 2011 Informa Healthcare USA, Inc.ISSN: 0277-0903 print / 1532-4303 onlineDOI: 10.3109/02770903.2011.604887
PEDIATRIC ASTHMA
Predicting Future Asthma Morbidity in Preschool Inner-City Children
NADIA N. HANSEL, M.D., M.PH.,1,2,∗ ELIZABETH C. MATSUI, M.D.,2,3 ROBERT RUSHER, M.D.,1
MEREDITH C. MCCORMACK, M.D.,1,2 JEAN CURTIN-BROSNAN,3 ROGER D. PENG, PH.D.,4 DEREK MAZIQUE,1
PATRICK N. BREYSSE, PH.D.,2 AND GREGORY B. DIETTE, M.D., M.HS.1,2
1Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.2Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
3Department of Pediatrics, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.4Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Background and aims. Children living in the inner city are particularly vulnerable to asthma. While we know much about factors that affectnear-term outcomes in inner-city children, there is little evidence to guide clinicians on what to expect in the coming years, especially inpreschool children. The purpose of our study was to determine which clinical and environmental factors are predictive of poor long-termasthma control in preschool inner-city children.Materials and methods. Baseline characteristics determined to be potential predictors of asthmaseverity were examined: demographics, asthma symptoms, medication use, healthcare utilization, early life medical history, family history,allergen exposure and allergic disease, and pollutant exposure. Bivariate and multivariate analyses were performed using logistic regressionto examine the association of predictors of asthma severity with healthcare utilization at 2 years. Results. Of the 150 children at baseline,the follow-up rate was 83% at 2 years; therefore, 124 children were included in final analyses. At baseline, the mean age was 4.4 years andparticipants were predominantly African-American (90%). Most of the children were atopic and 32.5% reported using inhaled corticosteroids.Nighttime awakening from asthma and a history of pneumonia were predictive of future poor control. Conclusion. Preschool children withnighttime awakening from asthma and a history of pneumonia may deserve closer monitoring to prevent future asthma morbidity.
Keywords asthma, inner city, preschool children
INTRODUCTION
Asthma is one of the most common chronic illnessesof childhood, affecting an estimated 6 million childrenin the United States alone (1). We know that childrenliving in the inner city are particularly vulnerable toasthma, including higher asthma prevalence and poordisease outcomes, with worse disease severity, increasedhospitalizations, and increased mortality (2–6). Whilewe know much about factors that affect near-termoutcomes in inner-city children, there is little evidenceto guide clinicians on what to expect in the comingyears, especially in preschool children. Parents of youngchildren with asthma want to know if the disease willstabilize, improve, or worsen, and healthcare practitionersneed to know which children will require more intensivefollow-up and medical services. It would be helpfulto identify clinical factors that could distinguish whichchildren will develop or continue to have troublesomesymptoms, especially as they prepare to enter school.
Cross-sectional studies have shown that certain factorsare associated concurrently with asthma control. Forexample, a recent study (7) investigated children andadolescents aged 4–17 years and found that uncontrolledasthma was linked to self-reported asthma severity and
∗Corresponding author: Nadia N. Hansel, M.D., M.PH., Johns HopkinsAsthma & Allergy Center, 5501 Hopkins Bayview Circle, Room 4B69,Baltimore, MD 21224, USA; Tel: (410) 550-4887; Fax: (410) 550-2612;E-mail: [email protected]
to reported history of recent cold, flu or sinus infections,history of exacerbation, and caregiver unemployment. Inanother cross-sectional study of children aged 4–18 years,race/ethnicity, lower lung function, and immunoglobulinE (IgE) sensitization to cockroach were concurrentlylinked to asthma control. In one of the few studieslooking exclusively at preschool age children (2–5 years),factors found to precede exacerbations by only 1 dayincluded nighttime use of a short-acting bronchodilator(8). To date and to our knowledge, most studies have beencross-sectional or focused on very near-term outcomes;asthma morbidity predictors have varied from study tostudy; and none has examined long-term predictors ofasthma severity in a group confined to preschool-agedchildren in the inner city.
Pediatricians commonly collect information fromparents about the child’s early life history, current asthmahealth, medication use, environmental exposures, andfamily health history. The predictive value of suchinformation for longer term prognosis has not beensufficiently studied. The purpose of our study was todetermine which, if any, clinical factors are predictive ofpoor long-term asthma control.
METHODS
Study Participants
The study population was composed of children whoparticipated in the observational study: Baltimore Indoor
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Environment Study of Asthma in Kids (9–11). At enroll-ment, participants were between 2 and 6 years of age andresided in one of nine contiguous zip codes in Baltimore,MD, USA. The participants were identified from asample of children with healthcare encounters withinthe previous 12 months at Johns Hopkins CommunityPhysicians or Bayview Pediatrics, the medical centersthat provide the majority of care to children living inthese inner-city zip codes. Eligibility criteria for childrenincluded: (1) doctor-diagnosed asthma, (2) symptoms oruse of asthma medications within the last 6 months, and(3) at least one healthcare encounter for asthma withinthe preceding 12 months (ICD-9 493.xx). Participantswere recruited between September 2001 and December2003, and written informed consent was obtained fromparents or legal guardians, and the Johns HopkinsMedicalInstitutional Review Board approved the study protocol.
Baseline Data Collection
Baseline data were collected using an interviewer-administered survey with closed-ended questions. Care-givers reported on household demographics, indoor envi-ronmental exposures (including allergens and pollutants),family history (asthma, hay fever, and eczema), thechild’s respiratory symptoms during the previous 2 weeks,and medication use (long-term controller [LTC] use andrescue medications use within the previous 2 weeks).The use of the following LTC medications was assessed:inhaled corticosteroids (ICSs), cromolyn and nedocromil,oral leukotriene modifiers, long-acting beta-agonists, andoral theophylline.
Asthma severity was categorized as intermittent, mildpersistent, moderate persistent, and severe persistentbased on reported daytime symptoms, nighttime symp-toms, reliever medication use, and activity limitation overthe prior 2 weeks, as recommended by the NationalAsthma Education and Prevention Program (NAEPP)guidelines (1).
Allergic sensitization status was assessed by skinprick testing (Multi-Test II, Lincoln Diagnostics, Decatur,IL, USA) to 14 common aeroallergens and 2 controls(histamine and glycerine) (Hollister-Stier Laboratories,Spokane, WA, USA and Greer Laboratories, Lenoir, NC,USA), as previously described (10,11). A positive skintest was defined as a net wheal diameter of at least 2 mm,and a child was considered atopic if he/she had at leastone positive skin test in the panel of allergens tested.Subjects also underwent blood draws, with serum samplesanalyzed for total IgE (kU/l) by CAP-RAST (PharmaciaDiagnostics, Uppsala, Sweden).
Environmental assessments included an inspection ofthe entire dwelling, and dust and air sampling wereconducted in the child’s bedroom. This location waschosen as the indoor monitoring site as it representswhere the child spends a substantial portion of time whileindoors. Household dust samples were collected from thechild’s bedroom as previously described (11) and assayedfor the allergens of cat (Fel d 1), dog (Can f 1), andcockroach (Bla g 1) using standard methods (12–16). The
limits of detection of the assay were 50 ng/g for Fel d 1and Can f 1, and 1 U/g for Bla g 1.
Air samples were collected following previouslydescribed procedures (11,17). Briefly, integrated airsampling of particulate matter (PM) was performed over3 days using PM10 (PM with an aerodynamic size lessthan 10 µm) and PM2.5 (PM with an aerodynamicsize less than 2.5 µm) and 4 l/min MSPTM impactors(St. Paul, MN, USA) loaded with 37 mm diameter,2.0 µm pore size, PALL TefloTM polytetrafluoroethylene(PTFE) membrane filters with polypropylene supportrings (Pall Corporation, Ann Arbor, MI, USA). Sampleswere collected using battery operated pumps pluggedinto house electrical service to assure 72 h of operation.Nitrogen dioxide (NO2) samples were collected for thesame period using passive Ogawa badges (11,18).
2-Year Follow-Up Data Collection
Participants were contacted after 2 years to completean interviewer-administered survey with closed-endedquestions. Asthma severity after 2 years of follow-upwas the primary outcome of interest; as with baselineasthma severity, it was determined by parent/guardianreport of the child’s symptoms over the previous 2weeks. Categories of asthma severity were dichotomizedas intermittent/mild persistent versus moderate/severepersistent. The secondary outcome of interest was acutehealthcare utilization (HCU) at 2 years, defined as anyunscheduled doctor’s visit, emergency department visit,or hospitalization for asthma in the previous 3 monthsand reported at the 2-year follow-up; responses weredichotomized as yes or no.
Statistical Analysis
We used descriptive statistics to characterize the patientsample, with proportions or means with standarddeviations applied where appropriate. Student’s t-test andFisher’s exact test were also used, where appropriate, todetermine differences between subjects lost to follow-upand those remaining in the study.
Baseline characteristics that were determined to bepotential predictors of future asthma morbidity wereidentified (Figure 1) and categorized as (1) demographics(age, race, gender, and caregiver education); (2) asthmasymptoms (symptoms of wheeze and cough during theprevious 2 weeks); (3) medication use (ICSs and short-acting beta-agonist); (4) healthcare utilization (HCU);(5) early-life medical history (birth weight and history ofpneumonia, bronchitis, prematurity [born 3 weeks early],being breast fed, being on a ventilator, and antibiotic usein first year of life, or previous 12 months); (6) familyhistory (mother and/or father with a history of atopy,hay fever, or asthma); (7) allergen exposure and allergicdisease (symptoms of rhinitis, symptoms of eczema);(8) exposure and/or sensitization to common householdallergens – mouse, cat, dog, cockroach); and (9) pollutantexposure (PM10, PM2.5, NO2, and total cigarettes smokedin the household).
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PREDICTING FUTURE ASTHMA IN PRESCHOOL CHILDREN 799
Asthma control at 2 years
• Symptoms of wheeze• Symptoms of cough
Baseline asthma characteristics
• Pneumonia• Bronchitis
Early childhood illness
• Healthcare utilization• Medication use
Medication/healthcare use
• Age• Race/ethnicity• Gender• Caregiver education level
Demographics
• Mother and father history ofAsthma
• Hay fever• Atopy
Family history
• PM2.5• PM10• NO2• Reported smoking
Pollutants
• Symptoms of rhinitis• Symptoms of eczema• Exposure and sensitization(positive skin test) to commonhousehold allergens
Allergens/allergic disease
FIGURE 1.—Potential baseline predictors of asthma severity at 2 years.Note: PM2.5, PM with an aerodynamic size less than 2.5 µm; PM10, PM with an aerodynamic size less than 10 µm; NO2, nitrogen dioxide.
To address covariates with missing data, we usedmultivariate imputation by chained equations (19).Bivariate analysis was performed using logistic regressionto examine the association of predictors shown inFigure 1 with asthma severity and healthcare utilizationat 2 years. Variables with a p-value <.1 in bivariateanalysis were included in the multivariable models.Results were reported as odds ratios (ORs) with 95%confidence intervals (CIs). All analyses were performedusing StataSE 10.1 (Stata Corporation, College Station,TX, USA), and a two-tailed p-value < .05 was used todetect statistically significant differences.
RESULTS
Study Population
Of the 150 children at baseline, 124 (83%) returnedfor the 2-year follow-up visit and were included infinal analyses. The mean age of these 124 children atbaseline was 4.4 years (range 2–6 years); participantswere predominantly boys (61%) and African American(90%). Most of the children were atopic and 32.5%reported using ICSs (Table 1). The use of other LTCmedication use was infrequent: cromolyn and nedocromil(3%), and leukotriene modifiers (7%). Nine childrenreported taking oral corticosteroids during the past 2weeks. Median baseline pollutant concentrations were33.5 mcg/m3 for PM2.5, 47.5 mcg/m3 for PM10, and24 ppb for NO2.
Characteristics between subjects included in the finalanalyses and those lost to follow-up were not significantlydifferent, except male subjects (61 vs. 38%, p = .04)and those with less educated caregivers were morelikely to attend the follow-up visit and therefore beincluded in the final analyses. There was no significantdifference in the proportion of children with mildasthma or moderate/severe disease between the twovisits. Almost half of the children were classified ashaving moderate/severe asthma at both baseline and the
2-year follow-up (44% and 43%, respectively). Despiteminimal change in the proportion of children with mildor severe disease, 48 children (38.7%) showed a changein their asthma severity (improvement or worsening) atthe follow-up visit. Specifically, 25 (20.2%) children hadimproved and 23 (18.5%) children had worsened withregard to disease severity at 2 years (Table 2).
TABLE 1.—Baseline participant characteristics.
n = 124
Mean age (range) 4.44 (2−6)Gender
Percentage of male (%) 61.3Race (%)
African-American 90.3Other 9.7
Inhaled corticosteroid (ICS) use 32.5Educational attainment of caregiver (%)
8th Grade/some high school 42.7High school graduate 42.0Some college or more 15.3
Recent healthcare utilization (HCU)(previous 3 months) (%)Urgent doctor visit 17.7Emergency department visit 25.8Hospitalization 3.2
Atopic (%) 67.6Baseline asthma control (%)
Mild intermittent/persistent 55.6Moderate/severe persistent 44.4
TABLE 2.—Asthma severity at baseline and 2 years.
2-Year asthma severity
Intermittent/mildpersistent
Moderate/severepersistent Total
Baseline asthma severityIntermittent/mild persistent 46 23 69Moderate/severe persistent 25 30 55
Total 71 53 124
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Baseline Predictors of Asthma Severity at 2-YearFollow-Up Visit
In bivariate analyses, children with recent HCU at base-line were three times more likely (OR = 3.06; 95% CI =1.43–6.53) to have moderate/severe persistent asthmasymptoms at 2-year follow-up, while children with areported history of ever having pneumonia were fourtimes more likely (OR = 4.44; 95% CI = 1.32–14.86)(Table 3). Reported antibiotic use in the 12 months priorto the baseline visit was borderline statistically associated(p = .052) with worse asthma severity. Similarly,baseline medication use (both short-acting beta-agonistand ICS use) and daytime and nighttime symptoms ofwheeze predicted increased asthma severity at the 2-yearfollow-up. Specifically, ICS use (OR = 2.45; 95% CI =1.14–5.31), beta-agonist use (OR = 1.10, 95% CI =1.02–1.18), wheeze without a cold (OR = 2.52; 95%CI = 1.21–5.26), and nighttime awakening due to wheeze(OR = 3.18; 95% CI = 1.29–7.57) were associatedwith having moderate/persistent asthma symptoms atfollow-up. Demographic factors, other measured earlylife exposures, markers of allergy/allergic disease, familyhistory, and in-home allergen and pollutant exposuresincluding PM and NO2 were not predictive of worseasthma symptoms at 2 years.
In the multivariable models, after adjusting for factorsassociated with higher asthma severity in bivariate anal-yses, a reported history of pneumonia (OR = 4.91; 95%CI= 1.14–21.15) and nocturnal wheeze (OR= 2.65; 95%CI = 1.02–6.93) were independently associated with riskof having moderate/severe persistent asthma symptomsat 2 years. Medication use and baseline healthcareutilization were no longer significant predictors of asthmasymptoms.
Baseline Predictors of Healthcare Utilization at the2-Year Follow-Up Visit
Children with acute healthcare visits and children whoreported wheeze without a cold at baseline were almost
TABLE 3.—Baseline predictors of asthma symptoms at 2-year follow-up.
Asthma symptoms(moderate/severe vs.intermittent/mild
symptoms)
Asthma symptoms(moderate/severe vs.intermittent/mild
symptoms)Unadjusted Adjusteda
Baseline severity 1.34 (0.99–1.81) 1.09 (0.71–1.66)Acute healthcare visit 3.06 (1.43–6.53) 1.72 (0.65–4.57)Inhaled corticosteroids
(ICSs)2.45 (1.14–5.31) 1.39 (0.52–3.72)
Beta-agonist use 1.10 (1.02–1.18) 0.99 (0.88–1.10)Wheeze without cold 2.52 (1.21–5.26) 1.32 (0.53–3.29)Woken with wheeze 3.18 (1.29–7.57) 2.69 (1.00–7.21)Pneumonia 4.44 (1.32–14.86) 5.39 (1.43–20.28)Antibiotic use 2.05 (0.99–4.25) 1.38 (0.59–3.20)Rhinitis 1.97 (0.96–4.06) 1.31 (0.54–3.20)Mother/father hay
fever1.94 (0.92–4.09) 1.37 (0.56–3.35)
Note: Bold values are those statistically significant by P < 0.05.aAdjusted for all variables shown in table (these include all variables associated withasthma symptoms in bivariate analyses with p < .1).
TABLE 4.—Baseline predictors of healthcare utilization (HCU) at 2-yearfollow-up.
HCU HCU
unadjusted adjusteda
Acute healthcare visit 2.84 (1.25–6.46) 1.83 (0.70−4.77)Inhaled corticosteroids (ICSs) 2.19 (0.96–5.00) 1.46 (0.53–4.06)Wheeze without cold 2.84 (1.25–6.44) 1.53 (0.56–4.21)Woken with wheeze 1.60 (0.68–3.79) 1.14 (0.43−3.05)Rhinitis 3.35 (1.45–7.76) 1.64 (0.61−4.44)Mother hay fever 2.91 (1.27–6.69) 2.39 (0.91−6.26)Atopic 2.31 (0.88–6.01) 2.28 (0.77−6.79)Eczema ever 2.46 (1.07–5.66) 2.22 (0.85−5.83)Caregiver education 1.63 (0.93–2.84) 1.06 (0.54−2.09)
Note: Bold values are those statistically significant by P < 0.05.aAdjusted for all variables shown in table (these include all variables associated withHCU in bivariate analyses with p < .1).
three times as likely to require healthcare utilization2 years later. Similarly, those with markers of allergicdisease, including a history of eczema (OR = 2.46; 95%CI = 1.07–5.66), rhinitis symptoms (OR = 3.35; 95%CI = 1.45–7.76), and a family history of mother withhay fever (OR = 2.91; 95% CI = 1.27–6.69) were morelikely to report healthcare utilization at 2 years. Baselinedemographic factors, history of pneumonia or bronchitis,and in-home allergen and pollutant exposures were notpredictive of HCU at 2 years.
After adjusting for factors associated with health-care utilization in bivariate analyses, all tested factorscontinued to show a trend toward predicting healthcareutilization at 2 years, though none met statisticalsignificance (Table 4).
DISCUSSION
Although poor, inner-city children suffer disproportion-ately from asthma morbidity, few studies have investi-gated which clinical and environmental factors predictfuture asthma morbidity in inner-city preschool children.Several studies have shown that children with asthmahave more lost days from school, activity restriction,and missed sleep which may lead to worse schoolperformance (20). Furthermore, it has been shown thatbeginning school with asthma independently predictslow achievement (21). This has several implications forchildren with asthma in the inner city who suffer highlevels of asthma severity and may have poor schoolperformance (20). Thus understanding which preschoolchildren will have worse asthma morbidity upon enteringschool age may help target those at higher risk of worseoutcomes. To our knowledge, no study has examinedlong-term predictors of asthma severity in a groupconfined to preschool-aged children in the inner city. Inthis study, we determined that certain information readilyavailable to clinicians is a strong predictor of worseasthma symptoms and healthcare utilization 2 years laterin inner-city preschool children. These clinical factors,namely nighttime awakening from asthma and a history ofpneumonia, were predictive of which children would havemore severe disease 2 years later. Therefore, children with
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PREDICTING FUTURE ASTHMA IN PRESCHOOL CHILDREN 801
these clinical risk factors may deserve closer monitoringto prevent future asthma morbidity.
The NAEPP guidelines recommend assessing noctur-nal awakening due to asthma symptoms when assessing achild’s history and selecting an asthma treatment plan (1).Prior studies have highlighted the importance of nocturnalasthma symptoms by demonstrating that nocturnal symp-toms were associated with children’s decreased schoolattendance and performance, and parents’ lower workattendance, independent of daytime symptoms (22). Inour study, children who awakened at night due to asthmasymptoms had worse asthma symptoms 2 years later,independent of baseline daytime symptoms or overallasthma severity. The finding that the presence of nocturnalsymptoms was more predictive of future disease severitythan overall baseline asthma severity supports the theorythat the presence of nocturnal symptoms is an importantprognostic indicator. Not only does this symptom requireshort-term management changes but it also necessitatesmore intensive, longer term follow-up.
A clinician can easily obtain a child’s clinical historyduring a routine office visit, including whether heor she has had pneumonia. Our results indicate that,in addition to recent nocturnal symptoms, childrenwith a previous occurrence of pneumonia had worseasthma symptoms 2 years after enrollment. Whetherhaving had pneumonia previously predisposes one toworse asthma symptoms through an altered immuneresponse or structural lung changes, or whether thoseat risk for worse asthma are more likely to developpneumonia or a lower respiratory illness remains unclear.However, the importance of early life infection hasbeen previously implicated as a risk factor for persistentwheeze in children and adults (23–25). Based on ourresults, early life pneumonia is an important clinicalfactor associated with children developing wheeze,and with the presence of worse symptom severityin those with already established asthma. The abovefindings show that nocturnal symptoms and previouspneumonia are predictive of worse asthma symptoms,regardless of baseline atopic status and environmentalexposures.
Numerous studies have suggested that markers ofallergic disease and environmental exposures are associ-ated with concurrent worse asthma symptoms and maybe predictive of future asthma symptoms in children(26–29). Specifically, the Epidemiology and NaturalHistory of Asthma: Outcomes and Treatment Regimens(TENOR) study revealed that patients with three ormore allergic triggers were two times more likelyto have a future exacerbation (30,31). The ChildhoodAsthma Management Program retrospectively comparedchildren with prior hospitalization with those withoutprior hospitalization over 12 months and noted thatmarkers of atopy, such as greater number of positiveallergy skin tests, higher serum IgE level, and greaterperipheral blood eosinophilia, were strongly associatedwith hospitalization in children with mild-to-moderateasthma (32). In our study, the presence of rhinitis,along with family history of atopic disease, tended
to be associated with worse asthma symptoms at 2years. Similarly, children with atopy, allergic symptomsincluding rhinitis and eczema, and a history of motherwith hay fever showed an overall trend toward increasedHCU at 2 years, after adjusting for other factors, includingbaseline healthcare utilization. Although allergic markersdid not have a statistically significant association withworse outcomes after adjustment for other factors,the overall trends support prior longitudinal studiesdemonstrating that markers of allergic disease tend tobe predictive of future asthma symptoms in children(26–29,33). This information may help identify childrenat risk, and therefore studies investigating the effect ofearly treatment of allergies on the natural history ofallergies and asthma are warranted.
We have previously demonstrated that inner-city chil-dren are exposed to high levels of indoor pollutants andallergens (11,17,34). We have also shown that increasingconcentrations of PM and NO2 measured over 72 h at3-month intervals, as well as exposure to high levelsof mouse allergen in mouse-sensitized individuals, wereassociated with increased asthma symptoms at the time ofhigher pollutant concentrations in the home (9,11,17,35).Similarly, previous studies have demonstrated allergenexposure such as mouse and cockroach are independentrisk factors for increased asthma morbidity in inner-citychildren (36). Gruchalla et al. (37) showed that schoolage children, aged 5–11 years, in the inner city withexposure and sensitization to allergens – in particular tocockroaches – had worse 2-year asthma morbidity in theInner City Asthma Study. Similarly, Illi et al. showedthat sensitization and exposure to perennial allergens inearly life predisposed children to loss of lung function andasthma at school age (33). The current results, however,show that baseline pollutant and allergen concentrationswere not predictive of future asthma severity or HCUat 2 years in inner-city preschool children. Pollutantlevels measured over a 72-h period or allergen exposuremeasured at a single time point may not be an accuratereflection of chronic exposure over a 2-year period,and measuring exposure concentrations repeatedly overlonger periods may be warranted to assess long-termrisk of exposure. Furthermore, given our smaller samplesize, we were limited in power for subgroup analysisto investigate whether sensitized individuals exposed toa particular allergen may be more predisposed to poorfuture asthma morbidity.
Our comprehensive baseline evaluation, includingbaseline measures of asthma severity, medication use, andallergen and pollutant environmental exposures, allowedfor a thorough evaluation of multiple factors which maycontribute to disease progression. All of the data regardingsymptoms, medication use, and HCU were collected bycaregiver report. Therefore, reported LTC use may differfrom verified use, and medication compliance was notassessed. In addition, a reported history of pneumoniaand early life infections may be particularly subject torecall bias; however, this recall bias is likely minimizedby the young age of the children at enrollment and theprospective design of the study where parents reported
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history of pneumonia at baseline without knowing if theirchildren would continue to develop significant asthmamorbidity at 2 years of follow-up. Objective measures ofairway inflammation (i.e., exhaled nitric oxide) and lungwere not available; therefore, we were unable to assesstheir importance or additional contribution to predictingfuture asthma severity and HCU. In addition, culturedata were not available, therefore we were unable todistinguish whether the association of pneumonia withincreased disease severity was due to a particular organ-ism of infection. Lastly, the demographic homogeneity ofour poor, mostly African-American, inner-city populationlimits generalizability, but is in fact a strength of ourstudy, as we are able to identify baseline clinical char-acteristics that are particularly relevant in a population athigh risk of suffering significant asthma morbidity.
In summary, inner-city preschool children with asthmawho report a history of pneumonia and nighttimesymptoms of wheeze have worse asthma symptoms 2years later. Findings from this study may help to identifychildren who will continue to contribute to the highasthma burden that exists among school-aged minoritychildren with asthma and those residing in the inner city.These findings suggest that by using information readilyavailable to them, clinicians may identify preschool ageinner-city children who may be at risk for high asthmamorbidity in the future and who may require closermonitoring and asthma management.
ACKNOWLEDGMENTS
The study was supported by grants from the USEnvironmental Protection Agency (R82672401), NIEHS(ES09606), and NHLBI (HL04266, HL076322, andHL67850). None of the authors has any financial,consulting, or personal relationship with other peopleor organizations that could have influenced the workdescribed in this article.
DECLARATION OF INTEREST
The authors report no conflicts of interest. The authorsalone are responsible for the content and writing of thepaper.
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