The Canadian Childhood Asthma Primary Prevention Study: outcomes at 7 years of age.

Abstract

Avoidance of any one of the individual risk factors associated with childhood asthma has not been successful in preventing its development.
The purpose of this study is to determine the effectiveness of a multifaceted intervention program for the primary prevention of asthma in high-risk infants at 7 years of age.
Five hundred forty-five high-risk infants with an immediate family history of asthma and allergies were prospectively randomized into intervention or control groups prenatally. Intervention measures introduced before birth and during the first year of life included avoidance of house dust, pets, and environmental tobacco smoke and encouragement of breast-feeding with delayed introduction of solid foods. Assessment of outcomes at 7 years consisted of examination by pediatric allergists, methacholine inhalation tests, and allergy skin tests.
At 7 years, 469 of the 545 children were contacted, and 380 returned for further assessment. The prevalence of pediatric allergist-diagnosed asthma was significantly lower in the intervention group than in the control group (14.9% vs 23.0%; adjusted risk ratio, 0.44; 95% CI, 0.25-0.79). The prevalence of allergic rhinitis, atopic dermatitis, atopy (defined as positive skin test reactions to any common allergen), and bronchial hyperresponsiveness (defined as the provocative concentration of methacholine that induced a 20% decrease in FEV 1 from a postsaline value of less than 7.8 mg/mL) were not significantly different between the 2 groups. The prevalence of asthma (defined as wheeze without colds and the presence of bronchial hyperresponsiveness) was also significantly lower in the intervention group compared with the control group (12.9% vs 25.0%; adjusted risk ratio, 0.39; 95% CI, 0.22-0.71).
The multifaceted intervention program was effective in reducing the prevalence of asthma in high-risk children at 7 years of age.

Full text

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The Canadian Childhood Asthma Primary
Prevention Study: Outcomes at 7 years of age
Moira Chan-Yeung, MB,aAlexander Ferguson, MD,bWade Watson, MD,c
Helen Dimich-Ward, PhD,aRoxanne Rousseau, BSc,aMarilyn Lilley, RN,c
Anne DyBuncio, BSc,aand Allan Becker, MDcVancouver, British Columbia,
and Winnipeg, Manitoba, Canada
Background: Avoidance of any one of the individual risk
factors associated with childhood asthma has not been
successful in preventing its development.
Objective: The purpose of this study is to determine the
effectiveness of a multifaceted intervention program for the
primary prevention of asthma in high-risk infants at 7 years
of age.
Methods: Five hundred forty-five high-risk infants with an
immediate family history of asthma and allergies were
prospectively randomized into intervention or control groups
prenatally. Intervention measures introduced before birth and
during the first year of life included avoidance of house dust,
pets, and environmental tobacco smoke and encouragement
of breast-feeding with delayed introduction of solid foods.
Assessment of outcomes at 7 years consisted of examination
by pediatric allergists, methacholine inhalation tests, and
allergy skin tests.
Results: At 7 years, 469 of the 545 children were contacted,
and 380 returned for further assessment. The prevalence of
pediatric allergist–diagnosed asthma was significantly lower
in the intervention group than in the control group (14.9%
vs 23.0%; adjusted risk ratio, 0.44; 95% CI, 0.25-0.79). The
prevalence of allergic rhinitis, atopic dermatitis, atopy (defined
as positive skin test reactions to any common allergen), and
bronchial hyperresponsiveness (defined as the provocative
concentration of methacholine that induced a 20% decrease
in FEV1from a postsaline value of less than 7.8 mg/mL) were
not significantly different between the 2 groups. The prevalence
of asthma (defined as wheeze without colds and the presence
of bronchial hyperresponsiveness) was also significantly lower
in the intervention group compared with the control group
(12.9% vs 25.0%; adjusted risk ratio, 0.39; 95% CI, 0.22-0.71).
Conclusion: The multifaceted intervention program was
effective in reducing the prevalence of asthma in high-risk
children at 7 years of age. (J Allergy Clin Immunol
2005;116:49-55.)
Key words: Asthma, primary prevention
Asthmaandotheratopicdisordersarecomplexdiseases
because of interaction between environmental influences
and genetic predisposition. The rapid increase in the
prevalence of asthma observed in many countries is un-
likely to be related to genetic changes. A number of
intervention studies have focused on reducing one or
more environmental exposures in early life that might be
modified in families with a strong history of asthma.1-5
These environmental interventions have involved indoor
aeroallergens, environmental tobacco smoke, and breast-
feeding. Avoidance of individual risk factors has not been
successful in preventing the development of asthma.
We conducted a prospective, randomized controlled
study to determine the effectiveness of a multifaceted
intervention program in the primary prevention of asthma
in high-risk infants in 2 Canadian centers, Vancouver and
Winnipeg, in 1995.6The intervention program included
reduction of exposure to common indoor allergens,
avoidance of environmental tobacco smoke, encourage-
ment of breast-feeding, and delayed introduction of other
foods during the first 12 months of life. We hypothesized
that intervention during this window of opportunity has
thepotentialforlong-termmodificationoftheinfant’srisk
forasthmadevelopment.Wehavepreviouslyreportedthat
the prevalence of possible asthma was significantly
reduced by 34% and 40% in the intervention group
compared with the control group at 12 and 24 months of
age,respectively.6,7Thisisareportoftheoutcomesofthis
cohort at 7 years of age.
METHODS
Study population
The cohort has been described in previous reports.6,7Briefly,
infants at high risk for asthma development, defined as those with at
least one first-degree relative with asthma or 2 first-degree relatives
with other IgE-mediated allergic diseases(atopic dermatitis, seasonal
or perennial allergic rhinitis, or food allergy), were identified during
the mother’s third trimester of pregnancy. Families were randomly
allocated to our multifaceted intervention (n = 279) or to the control
group (n = 266). There were 4 pairs of twins at birth. At 7 years of
Fromathe Occupational and Environmental Lung Disease Unit, Department
of Medicine, and
University of British Columbia, Vancouver, andcthe Section of Allergy
and Clinical Immunology, Department of Pediatrics and Child Health,
Manitoba Institute of Child Health, University of Manitoba, Winnipeg.
Supported by the Canadian Institute of Health Research, the British Columbia
Lung Association, and the Manitoba Medical Service Foundation.
Received for publication January 18, 2005; revised March 23, 2005; accepted
for publication March 24, 2005.
Available online June 1, 2005.
Disclosure of potential conflict of interest: A; authors—none disclosed.
Reprint requests: Moira Chan-Yeung, MB, Respiratory Division, Department
of Medicine, 2775, Heather Street, Vancouver, BC, Canada V5Z 3J5.
E-mail: myeung@interchange.ubc.ca.
0091-6749/$30.00
? 2005 American Academy of Allergy, Asthma and Immunology
doi:10.1016/j.jaci.2005.03.029
bthe Division of Allergy, Department of Pediatrics,
49
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Abbreviations used
BHR: Bronchial hyperresponsiveness
OR: Odds ratio
PC20: Provocative concentration of methacholine that
induced a 20% decrease in FEV1from
postsaline value
RR: Relative risk
age, 80 (14% of the cohort) families were lost to follow-up. The
number of families that dropped out was not significantly different
betweenthe2groups.Ofthe466families(3pairsoftwins)thatcould
be contacted, 250 in the intervention and 219 in the control group
completedaquestionnairebyinterviewortelephone.Inaddition,202
in the intervention group and 178 in the control group were assessed
bya pediatricallergistineachcenter; ofthese,186inthe intervention
group and 164 in the control group also underwent a methacholine
inhalation test (Fig 1).
Study protocol
Home visits were carried out during the third trimester of
pregnancy and at 2 weeks and 4, 8, 12, 18, and 24 months after the
birthofthechild.Duringtheinitialvisit,astandardizedquestionnaire
was completed by trained interviewers to obtain information relating
to the demographic and health characteristics of the families, and the
children were randomly assigned to the intervention or control group
after theinitial assessment. The controlgroupfollowedthe usualcare
recommended by their primary care physicians.
Intervention measures during the
first year of life
The multifaceted intervention program implemented before birth
and during the first year of life has been described previously.4,5
Briefly, it consisted of the following: (1) house dust mite control
measures that included encasing parents’ and infants’ mattresses
and box springs with vapor-impermeable covers, hot water wash of
all bedding weekly, and application of benzyl benzoate powder
(Acarosan powder; Bencard Laboratories-SmithKline Beecham Inc,
Mississauga, Ontario) to carpets in bedrooms and benzyl benzoate
foam to the upholstered furniture in the most commonly used room
before and at 4 and 8 months after birth; (2) pet avoidance measures
consistingofremovalofcats,dogs,orbothfromthehomeand,where
this was not possible, instructions to keep pets outside the home or at
least outside the infant’s bedroom; (3) avoidance of environmental
tobacco smoke, including counseling parents on smoking cessation
and instructing families to keep their homes smoke free; and (4)
encouragement ofmotherstobreast-feedfor atleast4monthsandfor
the first year if possible and to delay introduction of other foods until
6 months of age. Partially hydrolyzed whey formula (Good Start;
Nestle Canada, Inc, North York, Ontario, Canada) was supplied for
supplementation if necessary and after weaning until 12 months of
age. Families were also encouraged to avoid use of daycare facilities
until after the first year of life. At each visit, the research nurse
reinforced the various avoidance measures.
The compliance and efficacy of the intervention measures have
been reported previously.6,8The average house dust mite allergen
(Der p 1 plus Der f 1) levels had been significantly reduced in the
intervention group compared with the control group at 12 and 24
monthsafter birth.6,8Althoughthe prevalenceof pets did not change,
there was less, but not statistically significantly less, cat allergen
exposure in the intervention homescompared with the control homes
(average Fel d 1, 1.68 vs 2.09 mg/g dust and 2.24 vs 2.5 mg/g dust
during 12 and 24 months, respectively).7Only 6% of the mothers in
the intervention group and 8.7% in the control group smoked at the
time of recruitment. The prevalence of mother smoking at 12 and 24
months after delivery were not different from baseline and also not
different between the 2 groups.6,8A high proportion of mothers in
both groups breast-fed their infants from birth (93% and 92% in the
intervention and control groups, respectively). At 8 months after
birth, differences in the prevalence of breast-feeding between the
intervention and control groups were significant (61% vs 50%,
P = .02). Only 19.5% of infants in the intervention group received
solids by the age of 4 months compared with 49.8% of the control
infants (P , .001). Significantly fewer children in the intervention
groupwere indaycare by 1year comparedwithcontrol infants(3.6%
vs 10.3%, P = .004).
Follow-up assessment
At 7 years, the research nurse completed a questionnaire on all
children contacted (n = 469), either when they returned for their
interview with the pediatric allergist or by telephone for those who
were unable to return or refused. The questionnaire used was
modified from that used in the International Study of Asthma and
Allergy in Childhood.9Respiratory symptoms asked about included
wheeze, attacks of wheeze and shortness of breath, nocturnal
awakening caused by wheeze, and the frequency and severity and
medication for treatment of wheeze attacks in the last 12 months.
On those who returned for further assessment, a pediatric allergist
ineachcenterwithoutknowledgeofthegroupallocationstatusofthe
children and who did not provide health care services to the families
conducted a structured interview with parents by using a standar-
dized form to record symptoms and physical findings (n = 380).
Spirometry and methacholine challenge testing were performed after
obtaining parental consent. The diagnosesof asthma and other atopic
disorders were clinical decisions made by the pediatric allergists
without knowledge of the results of the questionnaire, allergy skin
tests, spirometry, or methacholine challenge tests.
Allergy skin tests were performed with the epicutaneous method
by using a prick lanceter (Hollister-Stier, Omega Laboratories LTD,
Montreal, Quebec, Canada) with the following allergens (Hollister-
Stier, Omega Laboratories LTD): house dust mite (Dermatophagoides
FIG 1. Profile of clinical trial and follow-up assessment.
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50 Chan-Yeung et al
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pteronyssinus and Dermatophagoides farinae), cat, dog, cockroach,
Alternaria species, Cladosporium species, tree, grass and weed (rag-
weed) pollens, cow’s milk, egg white, wheat, soy, and peanut.
Histamine (1 mg/mL) was used as the positive control, and saline
was used as the negative control. The largest wheal diameter and its
perpendicularweremeasuredat15minutesaftertesting.Ameanwheal
diameter of 3 mm or greater than that elicited by the negative control
wasconsideredapositivereaction.Atopywasdefinedasapositiveskin
test reaction to one or more of these common allergens.
Methacholine (Methapharm Inc, Brantford, Ontario, Canada)
challenge testing was carried out according to the protocol of
Cockcroft et al.10Two children who had FEV1values of less than
70%ofpredictedvaluewereexcludedfrommethacholinetesting,but
both of them had a postbronchodilator change in FEV1of 12% or
more, and they were considered to have bronchial hyperresponsive-
ness (BHR). The provocative concentration of methacholine that
induced a 20% decrease in FEV1from postsaline value (PC20) was
determined. BHR was defined as a PC20of less than 7.8 mg/mL
methacholine.11The percentages of children whose FEV1values
decreased by 20% at 2, 4, 6, and 7.8 mg/mL methacholine were also
determined.
Follow-up assessment of all children was completed in 1 year.
Ethics
Ethics Committees of the University of British Columbia and the
University of Manitoba approved the study. Parents provided written
informed consent.
Data analysis
Our aim was to identify the size of the effect of our intervention
program on the point prevalence of asthma symptoms, pediatric
allergist–diagnosed asthma, allergic rhinitis and atopic dermatitis,
BHR, and atopy at 7 years of age. Distribution of outcome profiles
was compared between the control and intervention groups by using
x2analysis and t tests, where appropriate. Relative risks (RRs) with
95% CIs were estimated, and risk estimate–adjusted potential con-
founding variables included sex (male and female), first-born status
(yes and no), race (white, oriental, and others), socioeconomic status
(mother with and without postsecondary education), maternal and
paternalhistoryofasthma,andhistoryofasthmainoldersiblings(yes
and no for each) by using multiple regression analysis.
Statistical analysis was carried out with SPSS/PC Version 10
(SPSS, Chicago, Ill) and Stata statistical software, version 6.0 for
Windows 8 (Stata Corp, Tex).
RESULTS
The characteristics at baseline of the 380 children who
returned for an interview and physical examination at 7
years of age are shown in Table I. Except for a greater
percentage of mothers in the control group having post-
secondary education, personal and family characteristics
at baseline of those who came in for interview and exam-
ination at 7 years of age were not different from the
characteristics of those who only completed a question-
naire over the telephone and also were not different from
those of the 80 children who were lost to follow-up (data
not shown).
Table II shows the frequencies and adjusted RRs and
95% CIs of allergic rhinitis, atopic dermatitis, pediatric
allergist–diagnosed asthma, and asthma symptoms, nasal
symptoms, and skin rash in the last 12 months in the
control and intervention groups. The proportion of chil-
dren with pediatric allergist–diagnosed asthma was sig-
nificantly lower in the intervention group (14.9%)
compared with the control group (23.0%; adjusted RR,
0.44; 95% CI 0.25-0.79). The prevalence of allergic
rhinitis and atopic dermatitis was not different between
the 2 groups.
Theprevalenceandrelativerisksformostoftheasthma
symptoms in the last 12 months were lower in the
intervention group compared with the control group, and
this issignificant forwheeze andwheeze apartfrom colds.
The prevalence of emergency department visits for
wheeze or asthma was higher in the intervention group,
but the numbers were small.
Comparisons of asthma symptoms, nasal symptoms,
and skin rash in the control and intervention groups were
also carried out to include children who only had ques-
tionnaire data. The prevalence of asthma symptoms were
also significantly lower in the intervention group com-
paredwiththecontrolgroupforwheeze(16.8%vs26.0%;
adjusted odds ratio [OR], 0.55; 95% CI, 0.34-0.86),
TABLE I. Demographic characteristics of those who
were interviewed and examined by pediatric allergists
at age 7 years (n = 380)
Characteristics
Control
group
(n = 178)
Intervention
group
(n = 202)P value*
Male, N (%)
First born, N (%)
Ethnic, N (%)
Whites
Nonwhites
Mother received
postsecondary
education, N (%)
Family history of
asthma, N (%)
Mother
Father
Older sibs
Family history of other
allergic disorders, n (%)
Mother
Father
Older sibs
Smokers in the family
at birth, N (%)
Mother
Father
Others
Pets at home at birth, N (%)
Any
Cats
Dogs
City where the trial was
conducted, N (%)
Vancouver
Winnipeg
84 (47.2)
102 (57.3)
93 (46.0)
96 (47.5)
.837
.064
142 (79.8)
36 (20.2)
151 (84.8)
159 (78.7)
43 (21.3)
144 (71.3)
.899
.002
69 (38.8)
69 (40.1)
24 (13.5)
93 (46.0)
61 (31.1)
39 (19.3)
.177
.081
.132
140 (78.7)
121 (69.9)
61 (34.3)
152 (75.2)
122 (61.9)
80 (39.6)
.466
.124
.290
17 (9.8)
30 (16.9)
5 (2.8)
13 (6.4)
34 (16.8)
9 (4.5)
.341
1.00
.429
64 (36.0)
38 (21.3)
26 (14.6)
82 (40.6)
40 (19.8)
32 (15.8)
.398
.799
.776
86 (48.3)
92 (51.7)
100 (49.5)
102 (50.5)
.838
*Comparison of the 2 groups by using x2tests.
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wheeze apart from colds (8.0% vs 13.2%; adjusted OR,
0.54; 95% CI, 0.29-0.99), attacks of wheeze associated
with shortness of breath (16.5% vs 26.0%; adjusted OR,
0.53; 95% CI, 0.34-0.84), nocturnal awakening caused by
wheeze(9.2%vs11.9%;adjustedOR,0.70;95%CI,0.38-
1.28),andwheezeafter exercise (7.6%vs13.2%;adjusted
OR, 0.48; 95% CI, 0.26-0.90).
The mean FEV1values (92.7% 6 11.3% of predicted
value in the control group and 93.3% 6 12.5% of
predicted value in the intervention group) were not
different between children in the intervention and control
groups. The findings were similar for forced vital capacity
and FEV1/forced vital capacity (data not shown).
Fig2showsthattherewerenosignificantdifferencesin
theproportionsofchildrenwhohadadecreaseinFEV1by
20% at varying concentrations of methacholine between
the control and intervention groups. The prevalence of
BHR, defined as a PC20of less than 7.8 mg/mL, was
similar in the 2 groups. The prevalence of a PC20of less
than2 mg/mL washigher in theintervention groupthanin
the control group but not statistically significant.
The prevalence of asthma, defined as wheeze in the last
12 months and the presence of BHR, was 12.9% in the
intervention group and 25.0% in the control group
(adjusted RR, 0.39; 95% CI, 0.22-0.71; Table II).
Almost all (96.6%) of the children who came for an
interview and physical examination had allergy skin tests.
Although there were no significant differences between
groups, the intervention group had a higher proportion
of children with a positive skin reaction to one or more
common allergens than the control group (49.0% vs
41.6%, P = .349), especially to peanut (12.4% vs 6.9%,
P = .113; Fig 3).
DISCUSSION
This is a study of the outcomes at 7 years of a
prospective, randomized controlled trial with a multifac-
eted intervention program to decrease exposure to aller-
gens (both inhaled and ingested) and environmental
tobacco smoke in the first year of life of infants at high
risk for the development of asthma because of their family
history. We have previously reported a significant reduc-
tioninpossibleasthma(definedashaving,overthepast12
months, at least 2 distinct episodes of cough, each lasting
for2ormoreweeks;atleast2distinctepisodesofwheeze,
each lasting 1 or more weeks; or, in the absence of a cold,
at least one of the following: nocturnal cough at least once
a week and hyperpnea-induced cough or wheeze) in the
intervention group at 12 and 24 months of age.6,7
We now report a significant reduction of 56% in the
prevalence of pediatric allergist–diagnosed asthma asso-
ciated with a significant reduction of asthma symptoms,
including wheeze, attacks of wheeze with shortness of
breath, and wheeze associated with nocturnal awakening,
at 7 years of age in children in the intervention group
compared with children in the control group. There was
also a tendency toward the prevalence of bronchodilators
and anti-inflammatory drugs for the treatment of asthma
symptoms to be lower in the intervention group compared
with the control group. This multifaceted program, how-
ever, did not reduce the prevalence of BHR or sensitiza-
tion to common allergens in the intervention group. The
dissociation between the successful reduction of asthma
diagnosis by pediatric allergists and the more objective
tests of BHR and atopy is unlikely the result of incorrect
diagnoses made by the pediatric allergists because BHR
TABLE II. Symptoms in the last 12 months (questionnaire), diagnosis by pediatric allergists, and laboratory findings
in the control and intervention groups
Control group
Intervention
group
Adjusted
RR (95% CI)*P value
Symptoms in the last 12 mo
Wheeze
Wheeze apart from colds
?3 attacks of wheeze and SOB
Nocturnal awakening caused by wheeze
Wheeze after exercise
Cough at night, apart from colds
Used bronchodilator for wheeze
Used anti-inflammatory for wheeze
Emergency department visit for wheeze
Nasal symptoms apart from colds
Skin rash lasting for ?6 mo
Diagnosis by pediatric allergists
Asthma
Allergic rhinitis
Atopic dermatitis
Laboratory investigations
BHR (PC20?7.8)
Atopy (positive skin test to ?1 allergens)
Asthma (wheeze plus BHR)
N = 178
52 (29.2)
24 (13.5)
25 (14.0)
5 (2.6)
25 (14.0)
37 (20.8)
43 (24.2)
37 (20.9)
4 (2.2)
60 (33.7)
45 (25.3)
N = 202
35 (17.3)
15 (7.4)
22 (10.9)
3 (1.5)
17 (8.4)
40 (19.8)
39 (19.3)
31 (15.3)
10 (5.0)
80 (39.6)
45 (22.4)
0.42 (0.25-0.71)
0.39 (0.18-0.83)
0.61 (0.31-1.20)
0.51 (0.12-2.29)
0.48 (0.22-1.01)
0.84 (0.49-1.43)
0.63 (0.37-1.07)
0.63 (0.36-1.10)
1.68 (0.42-6.78)
1.23 (0.80-1.89)
0.83 (0.51-1.34)
.001
.015
.152
.359
.054
.520
.085
.107
.464
.344
.445
41 (23.0)
49 (27.5)
24 (13.5)
N = 164
117 (71.3)
72 (41.6)
41 (25.0)
30 (14.9)
64 (31.7)
25 (12.4)
N = 186
141 (75.8)
95 (49.0)
24 (12.9)
0.44 (0.25-0.79)
1.13 (0.71-1.81)
0.92 (0.49-1.73)
.006
.611
.791
1.27 (0.77-2.10)
1.23 (0.80-1.90)
0.39 (0.22-0.71)
.347
.349
.002
*Adjusted for differences in maternal education, maternal and paternal and older siblings with history of asthma, and male sex.
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and atopy are often present in individuals without asthma.
It was also not due to bias on the part of the pediatric
allergists because they were not aware of the group
allocation of the children or the results of methacholine
challenge tests and allergy skin tests when they were
conducting their assessment of the children. The prev-
alence of asthma, defined as BHR plus wheeze in the
last 12 months and derived from a questionnaire
interview conducted independently by research nurses,
was also significantly reduced by 61% in the interven-
tion group compared with the control group, providing
additional evidence for less asthma in the intervention
group.
The prevalence of BHR (defined as a PC20of less than
7.8mg/mL)inthiscohortatage7yearswas73.7%.Thisis
very high compared with the 16% to 30% prevalence
reported in other studies of schoolchildren.11-13The high
prevalence of BHR in the cohort is likely due to our
selection of a high-risk group on the basis of a history of
asthma and other atopic diseases among the first-degree
relatives for this study. Self-reported asthma was present
in 42.6%ofmothers,35.3%offathers,and13.4%ofolder
siblings. Another explanation for the high prevalence of
BHR could be related to the quality of the first methacho-
line challenge test attempted in this group of 7-year-olds.
Arshad and colleagues1,14-16carried out a primary
prevention of asthma study in 120 high-risk infants on
the basis of an atopic background. Using an intervention
focused on house dust mite control and food avoidance in
early life, the authors reported a dramatic reduction in
recurrent wheezing at 12 months. By 2 years of age, al-
though the prevalence of asthma was lower in the inter-
ventiongroupcomparedwiththatinthecontrolgroup,the
difference was not statistically significant.14At the age of
8 years, a significantly reduced risk of asthma symptoms,
such as current wheeze, nocturnal cough, and exercise-
induced wheeze, was found in the intervention group
compared with the control group.16The prevalence of
BHRdefinedasaPC20oflessthan8mg/mLattheageof8
years was lower (not statistically significant) in the inter-
vention group compared with the control group (32.7%
and 43.1%, respectively), considerably lower than the
prevalence of BHR in our cohort. However, a history of
familial asthma was present in a significantly smaller
proportion of their cohort (24.2% of mothers, 23.3%
fathers, and 26.7% siblings) compared with our cohort. In
FIG 3. Percentage of children with positive skin test reactions to various specific allergens in the intervention
and control groups.
FIG 2. Proportion of children with BHR according to different cutoff points of PC20in the intervention group (I)
and the control group (C).
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contrast to our study, Arshad et al16observed that atopy
was significantly reduced in the intervention compared
with the control group at 8 years (OR, 0.21; 95% CI, 0.07-
0.62).Theprevalenceofpositiveskintestresponsestoany
allergen in their control group was 46.8%, about the same
as our cohort. The history of allergy among first-degree
relatives was similar for the 2 cohorts.
There are 3 other prospective, randomized controlled
trials conducted in high-risk children recruited prenatally
for primary prevention of asthma using house dust mite
avoidance and other measures.2-5The intervention mea-
sures of the Australian Childhood Asthma Prevention
Study consisted of house dust mite avoidance measures
and dietary supplementation with omega-3 fatty acids.3,4
At 3 years, there was a significant reduction of 10% in the
prevalence of cough in atopic children but not in the
nonatopic children in the active diet group and a signif-
icant reduction in sensitization to house dust mite in the
active allergen avoidance group.4The Manchester Child-
hood Asthma and Allergy Prevention Study, using envi-
ronmental control measures, reported a significant
reduction in the prevalence of severe wheeze with short-
nessofbreath,prescriptionofmedicationforthetreatment
of wheezy attacks, and wheeze after vigorous playing,
crying, or exertion during the first year of life.2However,
themultinationalstudyofpreventionofallergyinchildren
in Europe, consisting of not only house dust mite avoid-
ance but also an educational package on the development
of allergies, did not find any difference in the prevalence
of sensitization to house dust mite or the prevalence of
various asthma symptoms at 2 years.5A longer period
of follow-up will be required to determine the effective-
ness of these intervention trials.
It is possible that both BHR and atopy, which are
genetically predetermined, cannot be easily modified by
decreasing exposure to allergens. We have shown that our
intervention measures applied during the first year of life
resulted in a lower level of exposure to indoor allergens,
reduced exposure to environmental tobacco smoke, and
a higher proportion of breast-feeding in the intervention
group.6These interventions reduced the prevalence of
possible asthma at 1 and 2 years of age and clinical
manifestations of asthma at 7 years. We speculate that it
might be possible that our multifaceted intervention
during an early-life window of opportunity had an effect
on the developing airways in these children. The genetic
determination of BHR and asthma might well be parallel
events that, when they intersect, have the potential to
induce clinical disease. Inflammatory airway changes,
airway subbasement membrane collagen deposition,
mucus gland hyperplasia and hypertrophy, and smooth
muscle hyperplasia and hypertrophy might relate to atopy
and could worsen constitutive airway responsiveness.
Early-life modification of one or more of these inducible
factorsmightaffecttheclinicalpresentation(symptomatic
BHR) and decreased clinical asthma in our cohort.17We
hypothesize that the intervention measures might have
reduced the degree of airway inflammation, which we did
not measure as an outcome at 7 years. Asthma at age 7
years, especially in the presence of atopy, is likely to
represent persistent disease.
It should be noted that our cohort consisted of highly
educated families, with the majority of mothers having
postsecondary education. This might have contributed to
the effectiveness of the intervention program. Moreover,
the prevalence of smoking among parents was low.
Differences in the effectiveness of primary prevention of
asthma and allergies could well be related to differential
efficacy of decreasing allergen exposure, given the pres-
ence of absence of prenatal or postnatal environmental
tobacco smoke exposure.
In conclusion, the multifaceted intervention program
applied during the first year of life for the primary
prevention of asthma in a group of high-risk children
significantly reduced the prevalence of pediatric allergist–
diagnosed asthma and asthma symptoms but not allergic
rhinitis, atopic dermatitis, atopy, or BHR at 7 years of age.
It will be important to reassess these children at age 11 to
12 years to determine whether the multifaceted interven-
tion program carried out during the first year of life has
been effective in decreasing the lifelong risk for asthma or
has merely postponed the onset of asthma.
We thank Michelle Dittrick, Maureen Sigurdson, Joan Brooks,
Henry Chan, Judy Passante, Lesley Stewart, Kathy Lee, Brenda
Gerwing,andVanjaDijakfor theirhardwork,whichmadethisstudy
possible.
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Correction
With regard to the May 2005 editorial entitled ‘‘Does obesity weigh heavily on the health of the human airway?’’
(2005;115:921-4):Inthesecondsentenceofthesectionentitled‘‘EXPERIMENTALEVIDENCEFORASSOCIATION,’’a
quotation was incorrectly attributed to an article in the May issue by S.A. Shore and J.J. Fredberg. In fact, the quotation is
from the article in the May issue by G. Fantuzzi (pages 911-9). The sentence should have appeared as follows:
Fantuzzi,8in an article in this issue, has quite rightly commented that ‘‘[t]he majority of studies published on
this topic are epidemiologic investigations; the paucity of basic research on the possible role of adipose tissue
in modulating asthma susceptibility and symptoms is quite striking.’’
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