 |
|
Day Care Attendance, Respiratory Tract Illnesses, Wheezing, Asthma, and Total Serum IgE Level in Early Childhood
Juan C. Celedón, MD, DrPH;
Augusto A. Litonjua, MD, MPH;
Louise Ryan, PhD;
Scott T. Weiss, MD, MS;
Diane R. Gold, MD, MPH
Arch Pediatr Adolesc Med. 2002;156:241-245.
ABSTRACT
| |
Background It has been hypothesized that day care–related infections may
explain the inverse relation between day care attendance in early life and
asthma in childhood.
Objective To examine the relation between day care attendance or respiratory tract
illnesses in the first year of life and wheezing and asthma in the first 4
years of life among children with a parental history of atopy who were followed
up from birth.
Results Day care attendance in the first year of life was inversely associated
with geometric mean total serum IgE level (12.9 [±1 SD = 3.3, 51.4]
IU/mL for day care vs 18.5 [±1 SD = 5.3, 64.7] IU/mL for no day care; P = .03) at 2 years of age but not significantly associated
with wheezing at or after 2 years of age. Having at least 1 physician-diagnosed
lower respiratory tract illness in the first year of life was significantly
associated with recurrent wheezing (odds ratio [OR], 2.0; 95% confidence interval
[CI], 1.0-4.1) and asthma (OR, 2.5; 95% CI, 1.1-5.5) at 4 years of age, but
not with any wheezing (infrequent and frequent) at 3 years or older. Illnesses
of the upper respiratory tract ( 1 physician-diagnosed upper respiratory
tract illness or 3 episodes of nasal catarrh) in the first year of life
were associated with any wheezing (frequent and infrequent) between the ages
of 1 and 4 years, but not with recurrent wheezing or asthma at 4 years of
age.
Conclusions Our results suggest that among children with a parental history of atopy
the protective effect of day care attendance in early life against the development
of atopy has begun by 2 years of age, and that a protective effect of day
care attendance in early life against wheezing may not be observed until after
4 years of age.
INTRODUCTION
THE PREVALENCE of asthma in the United States has increased significantly
during the past 30 years, making this respiratory disease a major public health
problem.1-2 It has been hypothesized
that the asthma epidemic in the United States and other developed countries
is due, at least in part, to reduced exposure to other children3
and a decreased risk for infections in early childhood.4
Approximately 60% of children in the United States attended day care
in 1995.5 Results of 2 recent studies conducted
in Germany6 and the United States7
have demonstrated an inverse association between day care attendance in early
life and the development of atopy,6 wheezing,7 and asthma7 later in
childhood. Since day care attendance is associated with an increased risk
for infectious illnesses of the upper (URI)8
and lower respiratory tract (LRI)9-10
in early life, these infectious illnesses may be partly responsible for the
observed protective effect of day care attendance on the development of childhood
asthma.
The Home Allergens and Asthma Study is a prospective birth cohort study
of children with a parental history of asthma or allergies in the Boston,
Mass, metropolitan area. We previously showed that day care attendance among
study participants was associated with an increased risk for physician-diagnosed
URIs and LRIs in the first year of life.11
In the present report, we examine the association between day care attendance
in the first year of life and wheezing and asthma in the first 4 years of
life and try to determine whether the observed association is due primarily
to day care–related respiratory tract illnesses requiring medical attention.
PATIENTS AND METHODS
The 505 infants with a history of allergy or asthma in at least 1 parent
were recruited between September 1, 1994, and August 31, 1996. The screening
and recruitment of families have been described elsewhere.12
Every 2 months, beginning when the child was 2 months of age, a telephone
questionnaire was administered to the child's primary caretaker until the
child's second birthday. Afterwards, interviews were conducted every 6 months.
Of the 505 children, 7 were excluded because they were followed up for no
more than 4 months during their first year of life. The study was approved
by the institutional review board of Brigham and Women's Hospital, Boston.
Day care attendance in the first year of life was treated as a binary
variable.11 Every 2 months during the child's
first year of life, the caretaker was asked: "Since we last spoke with you
on [date given], has your child had a pneumonia diagnosed by a doctor?" Other
bimonthly questions included whether a runny or stuffed nose or physician-diagnosed
croup, bronchitis, bronchiolitis, ear infection, or sinus trouble had occurred
since the previous questionnaire was administered. These variables were then
categorized as any vs no physician-diagnosed LRIs (ie, croup, bronchitis,
bronchiolitis, or pneumonia), any vs no physician-diagnosed URIs (ie, ear
infection and sinus trouble), and at least 3 vs fewer than 3 reports of runny
or stuffed nose (nasal catarrh).11
Sociodemographic and familial variables included the child's race and
annual household income,12 type of medical
insurance (none, private, and nonprivate), in utero exposure to smoking, breast-feeding
(as a binary and a categorical variable [never, exclusively for <4 months,
and exclusively for 4 months]), bottle-feeding in a bed or crib before
bedtime, parental history of asthma (ever diagnosed and ever diagnosed with
current symptoms), number of older siblings (as a continuous and as a categorical
variable [<3 vs 3]), and average number of cigarettes per day smoked
by all adults in the household.11
Wheezing was considered present at any time from 12 to 48 months of
age if at least 1 affirmative response was given to the question: "Since we
last spoke with you on [date given], has your child had wheezing or whistling
in the chest?" Every year—starting at 2 years of age—we also asked:
"How many attacks or episodes of wheezing has your child had in the past 12
months?" Recurrent wheezing at 4 years of age was defined as at least 2 episodes
of wheezing in the previous 12 months. Asthma at 4 years of age was defined
as physician-diagnosed asthma and at least 1 episode of wheezing in the 12
months preceding the interview.
Total serum IgE level at 2 years of age was measured by an enzyme-immunoassay
based on the sandwich technique (UniCAP; Pharmacia Diagnostics, Kalamazoo,
Mich). All values were converted to the log-natural scale for analysis.
We conducted the bivariate analysis using  2 and 2-tailed t tests. We used stepwise logistic regression to study
the relation between day care attendance in the first year of life and the
outcomes of interest (total serum IgE level at 2 years of age, and recurrent
wheezing and asthma at 4 years of age) while adjusting for potential confounders
and examining interactions. In the final models, we included those variables
that satisfied a change-in-estimate criterion (10% in the odds ratio [OR])
or that were significant at the P<.05 level. For
the longitudinal analysis of the relation between day care attendance in the
first year of life and wheezing in the first 4 years of life, we used proportional
hazard models, with repeated events on the same child being handled by the
method of Anderson and Gill.13 To examine age-dependent
associations, we calculated interaction terms between the age of the children
at each survey and the variables in the model.
RESULTS
CHARACTERISTICS OF THE COHORT AND DAY CARE EXPERIENCE
The characteristics of the 498 study subjects have been described in
detail elsewhere.11 Table 1 summarizes the main characteristics of the study participants.
Of the 238 children (47.8%) who attended day care in their first year of life,
161 (67.6%) attended in a home setting; 52 (21.8%), a nonresidential setting;
and 25 (10.5%), both (mixed day care).11 Among
these 238 children, 50 (21.0%) attended day care with at least 10 children.
All 238 children attended day care for at least 5 hours per week and for at
least 1 month; 109 (45.8%) attended day care for at least 6 months, at least
3 days per week, and at least 4 hours per day.
|
|
|
|
Table 1. Characteristics of Children in the Cohort*
|
|
|
Of the 498 study participants, 461 (92.6%) were followed up to 4 years
of age. No statistically significant differences in sex, day care attendance
in the first year of life, respiratory tract illnesses in the first year of
life, and parental history of asthma were found between those with and without
4-year follow-up. Subjects who dropped out of the study before 4 years of
age were significantly more likely to come from low-income families and to
not be breastfed in the first year of life than subjects who underwent 4 years
of follow-up. Of the 498 participating children, 230 (46.2%) underwent a measurement
of total serum IgE level at 2 years of age. No significant differences in
day care attendance or respiratory tract illnesses in the first year of life
were found between those with and without total serum IgE measurements at
2 years of age.
RELATION BETWEEN DAY CARE ATTENDANCE OR RESPIRATORY TRACT ILLNESSES
IN THE FIRST YEAR OF LIFE AND RECURRENT WHEEZING AND ASTHMA AT AGE 4 YEARS
As in our previous study,11 the amount
of time that the children spent in day care during the first year of life
was not associated with the outcomes of interest. Since the estimates of the
association between day care attendance in the first year of life and the
outcomes of interest were similar, whether the child attended day care in
the first or second 6 months of life, we combined attendance in the first
and second 6 months of life.
Table 2 summarizes the results
of the analysis of the relation between day care attendance or respiratory
tract illnesses in the first year of life and recurrent wheezing and asthma
at 4 years of age. There was no significant association between day care attendance
in the first year of life and recurrent wheezing or asthma at 4 years of age.
Although children who had at least 1 physician-diagnosed LRI in the first
year of life had increased odds of having recurrent wheezing or asthma at
4 years of age, we found no significant association between URIs (physician-diagnosed
URIs or 3 episodes of nasal catarrh) in the first year of life and recurrent
wheezing or asthma at 4 years of age. We found no association between the
number of older siblings and recurrent wheezing or asthma at 4 years of age.
|
|
|
|
Table 2. Relation Between Day Care Attendance or Physician-Diagnosed
Infectious Lower Respiratory Tract Illnesses in the First Year of Life and
Recurrent Wheezing and Asthma at 4 Years of Age*
|
|
|
To examine whether the association between physician-diagnosed LRIs
in the first year of life and recurrent wheezing or asthma at 4 years of age
was due to reverse causation, we repeated the multivariate analysis after
excluding children who wheezed in the first year of life. Among the 280 children
who did not have any wheezing episodes in the first year of life, there was
no significant association between physician-diagnosed LRIs in the first year
of life and recurrent wheezing (OR, 1.7; 95% confidence interval [CI], 0.5-5.8)
or asthma (OR, 0.4; 95% CI, 0.1-3.8) at 4 years of age.
LONGITUDINAL ANALYSIS OF THE RELATION BETWEEN DAY CARE ATTENDANCE OR
RESPIRATORY TRACT ILLNESSES IN THE FIRST YEAR OF LIFE AND ANY WHEEZING IN
THE FIRST 4 YEARS OF LIFE
The results of the multivariate longitudinal analysis of the relation
between day care attendance or respiratory tract illnesses in the first year
of life and the primary caretaker's report of wheezing (infrequent and frequent)
throughout the first 4 years of life are summarized in Table 3. We found a significant interaction between day care attendance
or physician-diagnosed LRIs in the first year of life and age. The risk for
wheezing associated with day care attendance in the first year of life decreased
with increasing age, with no significant day care–related risk for wheezing
at 2 years of age. Although the risk for wheezing associated with physician-diagnosed
LRIs in the first year of life decreased significantly with age, the risk
for wheezing associated with physician-diagnosed URIs or at least 3 episodes
of nasal catarrh in the first year of life was increased throughout the first
4 years of life.
|
|
|
|
Table 3. Multivariate Longitudinal Analysis of the Relation Between
Day Care Attendance in the First Year Life and Wheezing in the First 4 Years
of Life*
|
|
|
DAY CARE ATTENDANCE IN THE FIRST YEAR OF LIFE AND TOTAL SERUM IgE LEVEL
AT 2 YEARS OF AGE
The geometric mean (± 1 SD) total serum IgE level at 2 years
of age was significantly lower in children who attended day care in their
first year of life than that in children who did not (12.9 [3.3, 51.4] IU/mL
vs 18.5 [5.3, 64.7] IU/mL; P = .03). This difference
was not significantly changed after adjusting for sex and household income.
There was no significant association between physician-diagnosed respiratory
tract illnesses or at least 3 episodes of nasal catarrh in the first year
of life and the children's total serum IgE level at 2 years of age.
COMMENT
Our study is unique in that we included detailed information on exposure
to day care and URIs and LRIs in the first year of life, a time when exposure
to day care or respiratory tract infections may influence the development
of the immune system.6-7,14
Among children with parental history of atopy, the risk for wheezing associated
with day care attendance in the first year of life decreased significantly
with age. At 2 years of age, day care attendance in the first year of life
was inversely associated with total serum IgE level, but not significantly
associated with wheezing.
In a longitudinal birth cohort study, children with greater exposure
to older siblings at home or day care were more likely to have frequent wheezing
at 2 years of age, but significantly less likely to have frequent wheezing
or a high total serum IgE level at 6 years of age than those with less exposure
to other children.7 Cross-sectional studies
of German6 and Italian15
children also showed an inverse association between day care attendance in
early life and atopy6 and persistent wheezing
at school age.15 Our longitudinal finding of
an inverse association between day care attendance in the first year of life
and total serum IgE level among children with a parental history of atopy
suggests that the protective effect of day care attendance in early life on
the development of atopy has begun by 2 years of age. The lack of a significant
inverse association between day care attendance in the first year of life
and asthma or wheezing at 4 years of age in our study is likely because wheezing
in early childhood may be related to infections in children with small airways
or to allergic inflammation of the airways.15
Since day care attendance in our study was positively associated with an increased
risk for infectious respiratory tract illnesses in the first year of life11 but inversely associated with a marker of atopy at
2 years (total serum IgE level), it may not be possible to observe a protective
effect of day care attendance in early life on wheezing until the children
are older.
In our study, having at least 1 physician-diagnosed LRI in the first
year of life was associated with increased odds of recurrent wheezing and
asthma at 4 years of age. Reverse causation is a plausible explanation for
our findings, as the observed association between physician-diagnosed LRIs
in the first year of life and recurrent wheezing or asthma at 4 years of age
was no longer significant once children who wheezed in the first year of life
were excluded from the analysis. Thus, children who are true asthmatic patients
may be predisposed to infectious LRIs in early life. An alternative explanation
for our findings is that some of the LRIs in our study may have been due to
respiratory syncytial virus, an infectious illness that is associated with
wheezing in early life16 and up to 11 years
of age.17 Our findings are in agreement with
those of 2 longitudinal birth cohort studies of Norwegian18
and German14 children. In the Norwegian study,
a strong association was found between parental report of infectious LRIs
in infancy and asthma at 4 years of age.18
The German investigators found a strong association between infectious LRIs
in the first 3 years of life and asthma and current wheezing at 7 years of
age.14 This association was no longer significant,
however, when wheezing LRIs were excluded from the analysis.
We found that having at least 1 physician-diagnosed LRI in the first
year of life was associated with an increased risk for wheezing (infrequent
and frequent wheeze) at 1 and 2 years of age but not at 3 or 4 years of age.
This finding is likely explained by airway growth resulting in a decreased
risk for wheezing related to infectious LRIs in early life, particularly among
children with infrequent wheezing and no maternal history of asthma.19
We found that URIs (physician-diagnosed URIs or 3 episodes of nasal
catarrh) in the first year of life were significantly associated with wheezing
(infrequent and frequent) from 1 to 4 years of age, but not with asthma at
4 years of age. However, we found a nonstatistically significant trend for
an association between at least 3 episodes of nasal catarrh in the first year
of life and recurrent wheezing at 4 years of age, as none of the children
who had fewer than 3 episodes of nasal catarrh in the first year of life had
recurrent wheezing at 4 years of age. Among children with parental history
of atopy, URIs may be due to infection or allergic inflammation. Inflammation
of the nasal mucosa due to allergy or infection could lead to recurrent nasal
catarrh, physician-diagnosed sinus trouble, or eustachian tube dysfunction
with persistent middle ear effusions20 and,
perhaps, otitis media. Thus, the association between URIs and wheezing in
the first 4 years of life in our study may be due to concurrent infectious
or allergic inflammation of the lower airways. Nafstad and colleagues18 found a positive association between having otitis
media in the first year of life or the common cold in the first 6 months of
life and asthma at 4 years of age.
We recognize several limitations to our findings. First, since most
of the subjects participating in our study attended day care in home settings
with a relatively small number of children, they may have been exposed to
a more modest burden of infectious and noninfectious illnesses than children
attending nonresidential day care centers. This could have resulted in limited
statistical power to detect an association between day care attendance in
the first year of life and asthma or recurrent wheezing at 4 years of age.
However, the predilection of study participants for home-based day care reflects
the general experience in the greater Boston area, where approximately 76%
of licensed day care is provided in a home setting.11
Second, we assessed the presence of respiratory tract illnesses in early life
by means of parental report and did not make an attempt to measure asymptomatic
infections. As previously mentioned, illnesses of the respiratory tract among
children with a parental history of atopy may be due to moderate to severe
infection, allergy, or both. Third, other investigators have found an inverse
association between recurrent nasal catarrh and asthma at 7 years of age.14 Since we have followed up children to 4 years of
age, we do not yet know what the relation between URIs and asthma will be
when the children reach school age.
CONCLUSIONS
Our results suggest that the protective effect of day care attendance
in early life against the development of atopy has begun by 2 years of age,
and that a protective effect of day care attendance in early life against
wheezing may not be observed until after 4 years of age. Among children with
a parental history of atopy, the association between illnesses of the respiratory
tract in the first year of life and wheezing in the first 4 years of life
may be due to infections and/or may be the early manifestation of an atopic
predisposition. Further follow-up of our study cohort should help us to clarify
the relation between day care attendance or respiratory tract illnesses in
early life and childhood asthma and atopy.
| What This Study Adds
Day care attendance in early life is inversely related to atopy and
asthma among children of school age. Little is known about the relation between
day care attendance or respiratory tract illnesses in early life and wheezing
and asthma in early childhood, particularly among children with a parental
history of atopy.
Our findings among children with parental history of atopy suggest that
an inverse relation exists between day care attendance in early life and atopy
by 2 years of age, but that any inverse association between day care attendance
in early life and wheezing may not be evident until after 4 years of age.
In children at high risk for atopy, the positive association between illnesses
of the upper and lower respiratory tract and wheezing in the first 4 years
of life may be due to infections and/or be the early manifestation of an atopic
predisposition.
|
|
AUTHOR INFORMATION
Accepted for publication November 14, 2001.
This study was supported by grant AI35786 from the National Institutes
of Health, Bethesda, Md. Dr Celedón is supported by a Charles A. King
Trust Fellowship Award, Boston.
We thank Jaylyn Olivo, MS, for her editorial assistance and Diane Sredl,
MPH, for her assistance with computer programming.
Corresponding author and reprints: Juan C. Celedón, MD, DrPH,
Channing Laboratory, 181 Longwood Ave, Boston, MA 02115 (e-mail: juan.celedon{at}channing.harvard.edu).
From the Channing Laboratory, Department of Medicine, Brigham and Women's
Hospital (Drs Celedón, Litonjua, Weiss, and Gold), the Division of
Pulmonary and Critical Care Medicine, Beth Israel Deaconess Medical Center
(Drs Celedón, Litonjua, Weiss, and Gold), Department of Medicine, Harvard
Medical School (Drs Celedón, Litonjua, and Weiss), and the Department
of Biostatistics, Harvard School of Public Health (Dr Ryan), Boston, Mass.
REFERENCES
| |
1. Mannino DM, Homa DM, Pertowski CA, et al. Surveillance for asthma—United States, 1960-1995. Mor Mortal Wkly Rep CDC Surveill Summ. 1998;47:1-27.
2. Centers for Disease Control and Prevention. Asthma—United States, 1982-1992. MMWR Morb Mortal Wkly Rep. 1995;3:952-955.
3. Strachan DP. Hay fever, hygiene, and household size. BMJ. 1989;299:1259-1260.
4. Martinez FD. Maturation of immune responses at the beginning of asthma. J Allergy Clin Immunol. 1999;103:355-361.
FULL TEXT
|
ISI
| PUBMED
5. West J, Wright D, Hausken EG. Child Care and Early Education Program Participation
for Infants, Toddlers, and Preschoolers. Washington, DC: Dept of Health, Education, and Welfare; 1995. Dept
of Health, Education, and Welfare publication (NCES) 95-824.
6. Krämer U, Heinrich J, Wjst M, Wichmann H-E. Age of entry to day nursery and allergy in later childhood. Lancet. 1999;353:450-454.
FULL TEXT
|
ISI
| PUBMED
7. Ball TM, Castro-Rodriguez JA, Griffith KA, Holberg CJ, Martinez FD, Wright AL. Siblings, day-care attendance, and the risk of asthma and wheezing
during childhood. N Engl J Med. 2000;343:538-543.
FREE FULL TEXT
8. Nafstad P, Hagen JA, Oie L, Magnus P, Jaakkola JJ. Day care centers and respiratory health. Pediatrics. 1999;103:753-758.
FREE FULL TEXT
9. Holberg CJ, Wright AL, Martinez FD, Morgan WJ, Taussig LM and Group Health Medical Associates. Child day care, smoking by caregivers, and lower respiratory tract
illness in the first 3 years of life. Pediatrics. 1993;91:885-892.
FREE FULL TEXT
10. Marbury MC, Maldonado G, Waller L. Lower respiratory illness, recurrent wheezing, and day care attendance. Am J Respir Crit Care Med. 1997;155:156-161.
ABSTRACT
11. Celedon JC, Litonjua AA, Weiss ST, Gold DR. Day care attendance in the first year of life and illnesses of the
upper and lower respiratory tract in children with a familial history of atopy. Pediatrics. 1999;104:495-500.
FREE FULL TEXT
12. Litonjua AA, Carey VJ, Burge HA, Weiss ST, Gold DR. Parental history and the risk for childhood asthma. Am J Respir Crit Care Med. 1998;158:176-181.
FREE FULL TEXT
13. Therneau TM, Grambsch J. Extending the Cox model. In: Modeling Survival Data: Extending the Cox Model. New York: Springer-Verlag NY Inc; 2000:185-186.
14. Illi S, von Mutius E, Lau S, et al and the MAS Group. Early childhood infectious diseases and the development of asthma up
to school age: a birth cohort study. BMJ. 2001;322:390-395.
FREE FULL TEXT
15. Rusconi F, Galassi C, Corbo GM, et al for the SIDRIA Collaborative Group. Risk factors for early, persistent, and late-onset wheezing in young
children. Am J Respir Crit Care Med. 1999;160:1617-1622.
FREE FULL TEXT
16. Wright AL, Taussig LM, Ray CG, Harrison HR, Holberg CJ. The Tucson Children's Respiratory Study, II. Am J Epidemiol. 1989;129:1232-1246.
FREE FULL TEXT
17. Stein RT, Sherrill D, Morgan WJ, et al. Respiratory syncytial virus in early life and risk of wheeze and allergy
by age 13 years. Lancet. 1999;354:541-545.
FULL TEXT
|
ISI
| PUBMED
18. Nafstad P, Magnus P, Jaakkola J, Jouni JK. Early respiratory infections and childhood asthma. Pediatrics. 2000;106:E38.
19. Martinez FD, Wright AL, Taussig LM, Holberg CJ, Halonen M, Morgan WJ for the Group Health Medical Associates. Asthma and wheezing in the first six years of life. N Engl J Med. 1995;332:133-138.
FREE FULL TEXT
20. Kraemer MS, Richardson MA, Weiss NS, et al. Risk factors for persistent middle-ear effusions. JAMA. 1983;249:1022-1025.
FREE FULL TEXT
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati
What's this?
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
Recurrent wheeze in early childhood and asthma among children at risk for atopy.
Ly et al.
Pediatrics 2006;117:e1132-e1138.
ABSTRACT
| FULL TEXT
Infections, medication use, and the prevalence of symptoms of asthma, rhinitis, and eczema in childhood
Cohet et al.
J. Epidemiol. Community Health 2004;58:852-857.
ABSTRACT
| FULL TEXT
Low-Normal Gestational Age as a Predictor of Asthma at 6 Years of Age
Raby et al.
Pediatrics 2004;114:e327-e332.
ABSTRACT
| FULL TEXT
Childhood Social Environment and Hodgkin's Lymphoma: New Findings from a Population-Based Case-Control Study
Chang et al.
Cancer Epidemiol. Biomarkers Prev. 2004;13:1361-1370.
ABSTRACT
| FULL TEXT
Day Care Attendance in Early Life, Maternal History of Asthma, and Asthma at the Age of 6 Years
Celedon et al.
Am. J. Respir. Crit. Care Med. 2003;167:1239-1243.
ABSTRACT
| FULL TEXT
Eat Dirt -- The Hygiene Hypothesis and Allergic Diseases
Weiss
NEJM 2002;347:930-931.
FULL TEXT
|
