Duration of Illness in Infants With Bronchiolitis Evaluated in the Emergency Department Frank D. Petruzella and Marc H.

Gorelick Pediatrics published online Jul 12, 2010; DOI: 10.1542/peds.2009-2189

The online version of this article, along with updated information and services, is located on the World Wide Web at: http://www.pediatrics.org

PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1948. PEDIATRICS is owned, published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, 60007. Copyright 2010 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

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Duration of Illness in Infants With Bronchiolitis Evaluated in the Emergency Department

AUTHORS: Frank D. Petruzella, MD, MS and Marc H. Gorelick, MD, MSCE
Division of Emergency Medicine, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin KEY WORD emergency medicine bronchiolitis respiratory syncytial virus ABBREVIATIONS RSVrespiratory syncytial virus ED emergency department RDAIRespiratory Distress Assessment Instrument CI condence interval IQRinterquartile range www.pediatrics.org/cgi/doi/10.1542/peds.2009-2189 doi:10.1542/peds.2009-2189 Accepted for publication Apr 27, 2010 Address correspondence to Frank D. Petruzella, MD, MS, Medical College of Wisconsin, Childrens Corporate Center, Suite 550, 999 N 92nd St, Milwaukee, WI 53226. E-mail: fpetruze@mcw.edu PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). Copyright 2010 by the American Academy of Pediatrics FINANCIAL DISCLOSURE: The authors have indicated they have no nancial relationships relevant to this article to disclose.

WHATS KNOWN ON THIS SUBJECT: Viral bronchiolitis is one of the most common illnesses of infancy. The majority of children evaluated in the ED for bronchiolitis are discharged from the hospital, where the burden of treatment falls on the caregivers. WHAT THIS STUDY ADDS: This report describes the duration of symptoms in children with bronchiolitis and provides information that clinicians can use to improve the accuracy of anticipatory guidance given to caregivers of children with bronchiolitis.

abstract
OBJECTIVES: To describe the duration of illness in infants with rsttime bronchiolitis who present to an emergency department (ED) and assess the burden of the illness on caregivers and families. METHODS: This was a prospective cohort study of infants younger than 12 months who presented to a tertiary care childrens hospital ED with a rst episode of bronchiolitis. Subjects were excluded if they had a history of bronchodilator use or immunocompromise. Demographic and clinical data were collected in the ED. Outcomes data were collected by weekly telephone interviews for 4 weeks or until the subject was free of cough for 24 hours. RESULTS: Ninety-ve infants were enrolled from November 2007 to March 2008. Median duration of symptoms was 15 days; 25% of the infants remained symptomatic after 21 days. Subjects with a history of eczema trended toward a longer median duration of symptoms when compared with those who did not (18 days [interquartile range (IQR): 15.524] and 15 days [IQR: 1119], respectively; P .055). Duration of symptoms did not signicantly vary with regards to respiratory syncytial virus status or secondhand smoke exposure. Subjects missed a median of 2.5 days (IQR: 0.55.5) of day care, and caregivers missed a median of 2 days (IQR: 1 4) of work. Of these infants, 37.1% (95% condence interval: 24.3 44.1) had a subsequent unscheduled medical visit. CONCLUSIONS: Infants seen in the ED for bronchiolitis have a prolonged disease course, with substantial burden to the family. Symptom duration may be inuenced by a propensity toward atopy. Clinicians may use this information for counseling families. Pediatrics 2010;126: e285e290

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Viral respiratory tract infections are among the most common infections in children. Specically in the infant population, the majority of these infections are caused by respiratory syncytial virus (RSV).1 In the United States, a preponderance of infants will remain outpatients for the duration of their illness; only an estimated 2% to 3% will require hospitalization.1,2 For infants evaluated in an emergency department (ED), caregivers rely on the anticipatory guidance provided before discharge as a guide for the expected course of illness in their child. A search of the literature, however, has revealed that, although the disease course in hospitalized patients has been well described, less is known about the duration of symptoms of ambulatory patients.3,4 Pediatric and infectious disease texts vary in the stated disease course, from 3 to 7 days to 3 weeks.58 In the current literature there are only 2 previous studies that reported the length of symptoms in nonhospitalized infants with bronchiolitis.9,10 The generalizability of these studies is difcult, however, because the rst study took place in an outpatient clinic in Cape Town, South Africa, and the second study was designed to evaluate viral etiology of bronchiolitis rather than illness duration.9,10 The variability of the natural history of bronchiolitis as stated in available resources can lead to inconsistent and inaccurate anticipatory guidance, which can lead to many unnecessary return visits to health care providers. The primary objective of this study was to describe the duration of illness in infants with rst-time viral bronchiolitis who presented to an ED located in a major metropolitan area in the United States. Data were also collected on the impact of this illness on the daily life of both infants and caregivers; the number of missed days of work and/or missed days of day care by the caregiver
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Day 0

Day 7

Day 14

Day 21

Day 28

ED visit Inclusion/exclusion criteria Demographic data Historical data Clinical data Nasal swab for RSV testing

Telephone interviews Presence/severity of cough Missed days of work Missed days of day care Unscheduled medical visits

FIGURE 1
Study design.

and infant, respectively, and the number of unscheduled medical visits made during the illness were evaluated.

METHODS
Study Overview This was a prospective cohort study of infants younger than 12 months with rst-time bronchiolitis (Fig 1). Potentially eligible infants were identied from a convenience sample of infants who presented to the Childrens Hospital of Wisconsin ED from November 1, 2007, through March 31, 2008, with a rst episode of acute bronchiolitis. The enrolling ED is within a large, tertiary care childrens hospital and has an annual patient volume of 60 000 visits. The study was approved by the Childrens Hospital of Wisconsin human research review board. Patient Enrollment To be eligible for enrollment, infants had to be younger than 12 months and had to have a clinical diagnosis of bronchiolitis made by the treating ED physician. Infants were determined to have bronchiolitis if they had lower airway disease (tachypnea, crackles, wheezing, and/or retractions) and a history of previous upper airway infection (nasal congestion and/or rhinorrhea).11 Infants were excluded for any of the following reasons: any previous episode of wheezing; bronchiolitis or asthma (as diagnosed by a physician); previous bronchodilator use; treat-

ment with corticosteroids in the 14 days before the current illness; immunosuppression; immunodeciency; or a diagnosis of croup or pneumonia by the treating ED physician. Infants were also excluded if the primary caregiver did not speak English. Eligible infants were approached for enrollment by trained clinical research assistants who screened all patients when on duty (15 hours/day on weekdays and 10 hours/day on weekends and holidays). Patients who presented to the ED outside of this time frame were identied for comparison to the study cohort by a medical record search for infants younger than 12 months with an International Classication of Diseases, Ninth Revision diagnosis of bronchiolitis who were seen in the ED during the enrollment season but during nonenrolling hours. Aggregate data including age, gender, race, and disposition for the nonenrolled cohort was then abstracted from the records. Baseline Data Collection After informed consent was obtained from the parent or guardian, 3 categories of baseline data were collected: demographic, historical, and clinical. Demographic data including age, gender, race, and ethnicity were collected from the ED medical record and directly from caregivers before patient discharge. Historical data obtained included the presence of risk factors for a severe bronchiolitis course (prema-

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turity, cardiac disease, and pulmonary disease), past history of atopy, and any family history of asthma or atopy (dened as having a rst-degree relative with asthma, eczema, or food allergies). Clinical data collected in the ED included the number of days of symptoms before presentation to the ED and the severity of current symptoms. To determine onset of illness, caregivers were asked, How many days ago did this illness start? Severity of symptoms was determined by the treating physician using the wheezing and retraction scales from the Respiratory Distress Assessment Instrument (RDAI).12 Infants also had a nasal swab collected during the ED stay for RSV testing. Caregivers were given the option to refuse RSV testing but still remain in the study. Follow-up Data Collection Caregivers were contacted for evaluation of cough, unplanned medical treatment, and missed days of work and/or day care via weekly telephone interviews for 4 weeks after discharge from the ED or until the illness had resolved. ED discharge is used to indicate the end of the ED stay and applies both to infants discharged from the hospital and those admitted for inpatient management. Before discharge from the ED, the parent or guardian was given a symptom diary for daily recording of symptoms and outcomes. Each page of the diary consisted of the exact questions that were asked of the caregiver during the follow-up telephone interviews. Caregivers were asked to refer to this diary during the interview to help minimize recall bias. Infants were considered lost to follow-up if 3 consecutive attempts to contact the parent or guardian at appropriate times were unsuccessful over a period of at least 3 days for 2 consecutive weeks.
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Outcomes The primary outcome was time from onset of symptoms to resolution of illness. The illness was considered resolved when the subject was free of cough for a 24-hour period. Cough was chosen as the index of illness duration for several reasons. First, it has been used in previous literature to estimate bronchiolitis symptoms.9,13 Second, it is a symptom that is often worrisome to parents. Third, it was chosen on the basis of the ease with which it can be monitored at home. Secondary outcomes were determination of difference in duration of illness between RSV-positive and RSV-negative bronchiolitis, as well as estimation of the burden of illness. Measures of this burden included days of missed day care by the infant, number of days of alternate or emergency day care arranged for by the caregiver, days of missed work by the caregiver, and frequency of unplanned return medical visits that resulted from the illness. Statistical Analysis Standard descriptive statistics were used for demographic, historical, and clinical data and for the primary and secondary outcomes. 2 testing was used to compare demographic and disposition data between the enrolled and missed eligible cohorts. Additional subgroup analysis for the primary outcome was performed by using Wilcoxon rank-sum tests, because duration of illness was found to have a nonnormal distribution. Survival analysis was also performed to evaluate time to symptom resolution both in the entire cohort and in subgroups. By ex-

pressing duration of illness as a median rather than a mean, and by performing survival analysis, statistical analysis was performed on the entire cohort without the exclusion of censored data. Minimum sample size was based on the primary study aim: the ability to estimate illness duration in the overall sample with a 95% condence interval (CI) of 1 day. On the basis of data available from Swingler et al,9 we assumed an average duration of 12 days with an SD of 3. A sample size of at least 50 would yield a 95% CI of 1 day, and 60 would be sufcient with an SD of 4. The study was also powered to nd a clinically important difference in duration of illness between RSV-positive and RSV-negative infants, assuming a 2:1 ratio of RSV-positive to RSVnegative infants. To detect a clinically relevant difference in duration of illness of 2 days between RSV groups with 90% power and an value of .05, we estimated a total sample size of 108.

RESULTS
Subject Enrollment During the enrollment period, 112 infants were enrolled onto the study (Fig 2). After enrollment, 9 of these infants were diagnosed by the treating physician as having pneumonia and, therefore, were subsequently excluded from the study, which left 103 enrolled children. Eight infants (8%) were lost to follow-up during the study period, which left 95 infants who completed the study and were included in data analysis.

112 Enrolled

103 Baseline data

9 Subsequently excluded

95 Complete data
8 Lost to follow-up

FIGURE 2
Subject enrollment.

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TABLE 1 Demographic, Historical, and Clinical

Characteristics of Infants (n
Demographic Age, median (IQR), mo Gender, % Female Male Race, % Black White Asian Mixed Unknown Ethnicity, % Hispanic Non-Hispanic Unknown Smoker living in home, % Historical, % History of eczema Family history of atopy History of prematurity Clinical RSV-positive (n 85), %a RDAI score, median (IQR) Discharged from the ED, %
a

95)
4 (37) 41 59 47 44 2 6 1 8 89 3 37 13 72 21 74 5 (39) 67

cohort were RSV-positive (74% [n 85]). Overall, infants had mild-tomoderate disease, with a median RDAI score of 5 and approximately twothirds of infants discharged from the ED. Rate of admission was not affected by history of atopy, history of prematurity, RSV status, or exposure to smoke in the home. Younger infants were admitted more frequently (60.9% of infants younger than 3 months admitted versus 26.3% of infants 3 to 6 months of age and 20.6% of infants 6 to 12 months of age; P .004). There was no difference found between the enrolled cohort and the missed eligible cohort with regards to age, gender, race, or disposition from the ED. Primary Outcome Median time to resolution of symptoms in the cohort was 15 days, and 25% of the infants continued to be symptomatic at day 20 of illness (Fig 3). At the end of the follow-up period, 11% of the infants continued to be symptomatic. Subgroup analysis (shown in Table 2) revealed a trend toward a prolonged duration of illness in those children with a history of eczema compared with those without a history of eczema (median: 18 days [inter-

TABLE 2 Subgroup Analysis of Duration of

Illness
Characteristic History of eczema Positive Negative Family history of atopy Positive Negative RSV status Positive Negative Exposure to tobacco smoke Positive Negative Disposition from the ED Discharged Admitted Duration of Illness, Median (IQR), d 18 (15.524) 15 (1119) P

.0547

16 (11.524) 14 (1115) 15 (1123) 15 (1217)

.0627

.6048

14 (1023) 15 (1220)

.2463

15 (1119) 15 (1125)

.6341

RSV testing was refused by 10 caregivers.

Subject Characteristics Subject characteristics are shown in Table 1. Just over one-third of the infants had passive exposure to tobacco smoke at home. Twelve infants (13%) had been given the diagnosis of eczema by a physician, and a family history of atopy was reported for the majority of them (72%). Of those tested, approximately three-quarters of the

quartile range (IQR): 15.524] vs 15 days [IQR: 1119], respectively; P .0547). A similar trend was seen in those with family history of atopy versus those with no atopic family history (median: 16 days [IQR: 11.524] vs 14 days [IQR: 1115], respectively; P .0627). No difference in illness duration was found with regards to RSV status, history of prematurity, exposure to tobacco smoke, or disposition from the ED. Secondary Outcomes Table 3 shows the burden placed on families by the illness in the form of missed day care, missed work, and return medical visits. In our study population, 34% of the infants attended day care. Caregivers reported that the inTABLE 3 Burden Placed on Families Due to
Bronchiolitisa
Day care missed (n 32), median (IQR), d Emergency day care (n 32), median (IQR), d Work missed (n 49), median (IQR), d Unscheduled medical visits (n 95), % (95% CI) 2.5 (0.55.5) 0 (03) 2 (14) 37.1 (27.547.5)

FIGURE 3
Duration of illness of cohort showing a median (IQR) duration of illness of 15 (1120) days, and 25% of infants continuing to be symptomatic at 20 days of illness.

a Only those infants who attended daycare and/or whose primary caregiver worked outside of the home were included in the daycare and work analysis.

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fants missed a median of 2.5 days (IQR: 0.55.5) of day care, and 75% of the children who attended day care missed at least 1 day because of the illness. Thirty-nine percent of the caregivers with children in day care reported having to make emergency alternate day care arrangements for at least 1 day. Of the 54% of caregivers who worked or attended school outside of the home, 78% reported missing at least 1 day of work or school because of their childs illness. The median number of days of work or school missed by caregivers was 2 days (IQR: 1 4). After disposition from the ED, 59 (61%) of the infants were reevaluated by a physician. Of these infants, 36 (37%) had at least 1 subsequent medical visit that was not recommended in the discharge instructions. The majority (78%) of these visits were to the primary physicians ofce; only 22% presented to the ED for reevaluation.

evaluate the duration of illness in infants with bronchiolitis who present to an ED. In the recent literature there are 2 previous studies that reported the length of symptoms in nonhospitalized infants with bronchiolitis.9,10 The rst study, by Swingler et al,9 revealed a median duration of illness of 12 days and that 40% of the patients continued to be symptomatic by day 14 of illness. Although the authors did not evaluate the impact on caregiver work attendance or infant day care attendance, it did report that 34% of the infants were seen for unscheduled medical visits within 28 days of enrollment.9 The ndings of the Swingler et al9 study may be difcult to generalize to the patient population seen in an urban ED in the United States, however. The study was conducted in an outpatient clinic in Cape Town, South Africa, which raises the question of demographic generalizability of the subject sample. Also, moderately to severely ill children were excluded from the study, which suggests that the study population examined was less ill than the typical population of infants with bronchiolitis seen in an ED. The second study, by Mansbach et al,10 reported a duration of illness of 3 to 8 days; however, this study was designed to evaluate viral etiology of bronchiolitis rather than duration of illness. It is unclear which symptoms the authors used to determine duration of illness or how often caregivers were contacted to assess progression of the illness. Results of previous studies have demonstrated that early infection with bronchiolitis is associated with prolonged and recurrent wheezing in some children.18,19 There is also epidemiologic evidence to suggest a link between bronchiolitis in infancy and development of asthma later in life.2022 On the basis of these previous studies,

one could hypothesize that those children with a genetic predisposition toward asthma or atopic disease would have a more prolonged disease course. In our cohort, we observed a trend toward prolonged illness in infants with a diagnosis of eczema when compared with those without an atopic history. Similarly, those infants with rst-degree relatives diagnosed with atopic disease tended to have longer illness. Although these trends were not statistically signicant, our study was not powered to detect a difference between these groups. Therefore, although these infants may truly be at risk for a more protracted illness, the combination of small sample size in each subgroup and lack of power to detect a difference between these subgroups increased the likelihood of type II error in these analyses. As suggested by the duration of illness reported for this cohort, bronchiolitis can cause a signicant disruption in routine home life of infants with the disease. Results of previous studies have shown a delayed return to normal family routine and a detrimental effect on quality of life for infants and families after hospitalization for bronchiolitis.3,23 Our data are consistent with these ndings; approximately three-fourths of working caregivers in our cohort reported missed days of work or day care because of the illness. When one also considers that almost two-thirds of the infants were taken for subsequent medical evaluation at least 1 time during the course of the illness, and that more than half of these visits were unplanned, the signicance of the nancial and temporal burden placed on families becomes obvious. This study has several limitations. In general, when infants are selected by convenience sampling, the possibility exists that the cohort analyzed is not representative of the general population. Specically, in the case of respiratory illnesses
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DISCUSSION
Despite the ubiquity of viral bronchiolitis in the infant population, there remains no therapy that has proven to be consistently effective in ameliorating symptoms or shortening the duration of illness in children with bronchiolitis.1417 Therefore, in the ED setting, after evaluation and stabilization, often the most important role of health care providers is to provide accurate anticipatory guidance to the caregivers before discharge. To provide this guidance, however, providers must have accurate information in regards to the natural history of the disease in question. In this study, we found a median duration of illness of 15 days in infants seen in the ED, and almost 25% of the infants continued to be symptomatic 3 weeks after the onset of illness. To our knowledge, this is the rst prospective cohort study designed specically to
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in children, failing to enroll patients during the overnight hours could result in a study sample that is less symptomatic than the general population. Although we do not have RDAI scores for those infants who presented to the ED during the overnight hours, we found no difference between this cohort and the enrolled infants with regards to the proportion of infants who required admission. Using admission as a proxy for symptom severity, the study cohort enrolled during the daytime and evening hours seemed to have had a similar severity of illness as those missed during the overnight hours. Our cohort was enrolled at a single site during a single bronchiolitis season. As such, the possibility exists that the population from which our sample was drawn is not generalizable to other REFERENCES
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CONCLUSIONS
We have shown that infants evaluated in the ED with acute bronchiolitis have a prolonged disease course, with substantial burden placed on the family during the illness. Clinicians may use this information for counseling families in an attempt to reduce unscheduled return visits. Our data also suggest that symptom duration may be inuenced by an infants propensity toward atopy. Future study is required to determine the true role of atopic tendency in the duration of illness in bronchiolitis.

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Duration of Illness in Infants With Bronchiolitis Evaluated in the Emergency Department Frank D. Petruzella and Marc H. Gorelick Pediatrics published online Jul 12, 2010; DOI: 10.1542/peds.2009-2189
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