Environmental Factors and Asthma What We Learned From Epidemiological Studies An Issue of Immunology and Allergy Clinics 1st Edition Mark Eisner All Chapters Available
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Environmental Factors and Asthma What We Learned
from Epidemiological Studies An Issue of Immunology
and Allergy Clinics 1st Edition Mark Eisner Digital
Instant Download
Author(s): Mark Eisner
ISBN(s): 9781416063094, 1416063099
Edition: 1
File Details: PDF, 2.17 MB
Year: 2008
Language: english
Immunol Allergy Clin N Am
28 (2008) xiii–xiv
Foreword
Environmental Factors in Asthma
Whether you take the biblical quotationd‘‘for dust you are and to dust
you will return’’ (Genesis 3:19)dor the theory of evolution, which implies
that environmental changes triggered the biological evolution, it is all about
environment. We as biologists have recognized the power of genes ever since
Mendel demonstrated the principles of genetic inheritance, and Watson and
Crick resolved the structure and beauty of the double helix. The driving
power of genes in the expression of a phenotype is undeniable. Nonetheless,
phenotype is not the same as genotype, and we are yet to fully understand
the complexity of the gene–environment interaction. Our simple paradigm
of promoter-driven exon-based gene expression is losing its ground. We
now understand that the expression of a gene is far more complex. Gene ex-
pression is controlled by proximal and distant enhancers and silencers, epi-
genetic modulation of the gene locus, secondary regulation by microRNA,
gene splicing, single nucleotide polymorphism, and other factors. Many of
the foregoing processes are influenced by the environment.
Asthma, being a polygenic disease, is far more susceptible to environmen-
tal changes. Thus, research in the environmental aspect of asthma is very im-
portant. A comprehensive understanding of the environmental contribution
to asthma requires population-based case control and prospective epidemi-
ologic studies, which are extremely difficult to conduct. Nonetheless, signif-
icant progress has been made in this field. We have observed continued
evolution of the hygiene hypothesis. We have a better understanding of
0889-8561/08/$ - see front matter Ó 2008 Elsevier Inc. All rights reserved.
doi:10.1016/j.iac.2008.04.002 immunology.theclinics.com
xiv FOREWORD
Preface
The morbidity and mortality from asthma have increased greatly during
the past few decades in the United States and most developed countries.
Although recent developments in genetics have provided exciting break-
throughs in airway disease, genetic factors, by themselves, cannot explain
the dramatic increases in asthma prevalence and severity. Dramatic changes
in the environment have occurred concurrently with the asthma epidemic,
raising the possibility that environmental factors may be responsible for
the increased burden of asthma. Indeed, the alterations of the indoor and
outdoor environment are dramatic features of the twentieth and twenty-first
centuries. Changes in diet, body composition, and workplace conditions
have also occurred. In this issue of the Immunology and Allergy Clinics of
North America, we review recent epidemiologic studies that implicate the
environment as a cause of asthma and its exacerbation.
The term ‘‘environment’’ is broad and all encompassing. Indeed, it re-
flects all that is external to the human organism. For many, the term ‘‘envi-
ronment’’ connotes the outdoor environment and its pollution by traffic,
other sources of combustion, and industrial contamination. But for most
residents of industrialized countries, the majority of time, in excess of
90%, is spent indoors. Consequently, the indoor environment, which in-
cludes homes, schools, workplaces, and other public places, becomes
especially important. Although it is true that the outdoor (ambient)
environment greatly influences the indoor one by entrainment of air and
other substances, there are unique point sources of pollution, allergen expo-
sure, and viral infection indoors. And finally, the social environment, which
0889-8561/08/$ - see front matter Ó 2008 Elsevier Inc. All rights reserved.
doi:10.1016/j.iac.2008.04.001 immunology.theclinics.com
xvi PREFACE
reflects the broader context of our lives, may have important influences on
asthma.
Randomized controlled trials have become the gold standard for address-
ing many problems in clinical medicine and health. But such trials are not
suited to studying most of the effects of environmental exposures on health.
Although short-term exposure studies are conducted in highly controlled en-
vironments, they provide limited insight into the development of chronic
diseases such as asthma, which have a long induction period (ie, develop
over a long period of time). Ethical and logistic concerns preclude random-
izing human subjects to potentially hazardous exposures over a longer time
period. Therefore, epidemiologic methods are the best ones for assessing the
impact of environmental exposures on health outcomes, such as asthma and
other respiratory diseases.
In this issue, we review the evidence that exposures to indoor pollution
(passive smoking, indoor combustion), other indoor exposures (allergens,
viral infections, occupational exposures, dampness, mold), and outdoor pol-
lution (traffic, other ambient pollution) are important factors for the devel-
opment and clinical course of asthma. The issue also considers the social
environment and how it influences asthma status. The impact of diet and
obesity, which have changed markedly during the past several decades,
may also contribute substantively to the asthma epidemic. And living on
a farm, with exposure to microbes and allergens, has fascinating, and some-
times counterintuitive, effects on asthma induction and course. Finally, an
article on asthma and the inner city integrates the issues of pollutant and al-
lergen exposure that often occur concurrently in the urban environment.
Ultimately, the goal of epidemiology and public health is preventiondin
this case, prevention of asthma incidence and exacerbation. This issue eluci-
dates the impact of the environment, defined broadly, on asthma with the
goal of highlighting possible areas in which exposure prevention or remedi-
ation might decrease the burden of asthma.
The findings and conclusions in this report are those of the authors and do not necessar-
ily represent the views of the National Institute for Occupational Safety and Health.
* Corresponding author.
E-mail address: [email protected] (N.M. Sahakian).
Meta-analysis in 2007
A meta-analysis of 33 peer-reviewed epidemiologic studies on respiratory
health outcomes and home dampness or mold included studies published
from 1989 to 2006 [5]. The estimated OR for cough in adults was 1.52
(95% CI, 1.18–1.96); for cough in children 1.75 (95% CI, 1.56–1.96); for
wheeze in adults 1.39 (95% CI, 1.04–1.85); for wheeze in children 1.53
(95% CI, 1.39–1.68); for current asthma 1.56 (95% CI, 1.30–1.86); for
ever-diagnosed asthma 1.37 (95% CI, 1.23–1.53); and for asthma develop-
ment 1.34 (95% CI, 0.86–2.10). The investigators estimated that home
dampness or mold is associated with a 30% to 50% increase in respiratory
health outcomes.
Adults
In a study that investigated occupational exposures, researchers reviewed
medical records at clinics in a Swedish town covering a 1.5-year period to
identify cases of newly diagnosed asthma among 20 to 65 year olds [6]. Con-
trols were randomly selected from the Swedish population registry, lived in
the same town, and were matched by age and gender to cases. Response
rates and study numbers for cases and controls were 90% (n ¼ 120) and
84% (n ¼ 446), respectively. The OR (adjusted for occupational exposure
to dust, fumes, or vapors, childhood allergy symptoms, and ever smoking)
for workplace exposure to building mold or moisture damage that lasted
3 or more years and occurred before the year of asthma diagnosis (for cases)
or referent time (for controls) was 4.7 (95% CI, 1.5–14.3). Because this study
included agricultural and maintenance workers whose exposure may differ
in intensity and type from office workers in damp buildings, caution should
be exercised when applying these findings to workers of nonindustrial in-
door environments.
A study by Gunnbjörnsdóttir and colleagues used data from the 1990–1994
European Community Respiratory Health Surveys (ECRHS) and a follow-
up survey conducted in 1999–2001 [7]. Participants from four Nordic coun-
tries were 20 to 44 years old at the time of the initial survey. Response rates
and study numbers for the initial and follow-up surveys were 84% (n ¼
21,802) and 74% (n ¼ 16,190). New-onset asthma was defined as an asthma
attack or use of asthma medications during the past 12 months on the second
survey with negative responses to both of these questions on the first survey.
The OR (adjusted for age, study center, gender, body mass index, rhinitis,
smoking status, type of housing, age of building, and socioeconomic status)
for the association between the presence of home dampness anytime between
the two surveys and new-onset asthma was 1.13 (95% CI, 0.92–1.40) and thus
did not quite meet statistical significance. Associations for new-onset asthma
symptoms were significant. Researchers also investigated the remission of
asthma-like symptoms and found that presence of home dampness in-
between the two surveys significantly decreased remission of nocturnal dysp-
nea and nocturnal cough. Analysis of a subset (Swedish subjects, n ¼ 1854) of
second survey, also by Gunnbjörnsdóttir and colleagues, participants
demonstrated significant positive associations between home dampness
and dyspnea at rest, dyspnea after exertion, and nocturnal dyspnea [8].
A Finnish population-based incident case-control study compared 521
adults, who had newly diagnosed asthma (defined as reversible airways ob-
struction with at least one asthma-like symptom) identified over a 2.5-year
period, to 932 randomly selected controls who did not have asthma [9].
Response rates for cases and controls were 90% and 80%, respectively.
Cases and controls were 21 to 63 years old and lived within the same hospi-
tal district in South Finland. Workplace wall-to-wall carpeting and work-
place mold independently increased the risk for new-onset asthma.
Table 1
488
Epidemiologic studies investigating an association between indoor dampness or mold and new-onset asthma or new-onset asthma-like symptoms that use
odds ratios as a measure of risk
Reference Study design Environmental exposure Health outcome Odds ratio (95% CI)
Adults
Flodin and Longitudinal case-control study Reported workplace dampness New-onset physician-diagnosed 4.7 (1.5–14.3)
Jönsson [6] (20–65 years old) (mold or moisture damage)a asthma at age 20–65 years
Gunnbjörnsdóttir Prospective study with a 7.9-year Reported dampness (water New-onset asthma attack 1.1 (0.9–1.4)
et al [7] follow-up period (mean age damage, leakage, or mold or current use of asthma
at follow up: 40 years) growth) in the homeb medicationsc
New-onset wheezec 1.3 (1.1–1.5)
New-onset nocturnal dyspneac 1.3 (1.1–1.6)
New-onset nocturnal coughc
SAHAKIAN
1.3 (1.1–1.4)
Jaakkola et al [9] Population-based incident Reported visible mold or mold New-onset physician-diagnosed
case-control study odor at workc and asthma with both reversible
et al
(21–63 years old) – No wall-to-wall carpet at work airways obstruction and 1.4 (0.9–2.1)
– Wall-to-wall carpet at work a history of at least one 4.6 (1.1–19.4)
asthma-like symptom
Children
Wickman et al [12] Prospective study of a birth Reported water damage, Three or more episodes of 1.7 (1.3–2.4)
cohort from age 2 months windowpane condensation, wheezing after age 3 months
to 2 years of age visible mold, or mold odor when and either use of inhaled steroids
child was 2 months of age or symptoms suggestive of
bronchial hyper-reactivity
Emenius et al [13] Nested case-control study of One sign of dampness based Three or more episodes of 1.3 (0.8–2.2)
a birth cohort (2 years old) on home inspection wheezing after age 3 months
Three or more signs of dampness and either use of inhaled 2.7 (1.3–5.4)
based on home inspection steroids or symptoms suggestive
of bronchial hyper-reactivity
Pekkanen et al [15] Population-based incident Mold odor based on current New-onset physician-diagnosed 4.1 (0.6–26.0)
case-control study home inspection asthma or new referral
(1–7 years old) Visible mold based on current to hospital after two or 1.2 (0.7–2.1)
home inspection more attacks of wheezing
Visible mold in main living 2.6 (1.2–5.8)
area based on current
home inspection
Water damage in main living 2.2 (1.2–4.0)
489
490
Table 2
Epidemiologic studies investigating an association between indoor dampness or mold and new-onset asthma that use incidence rate ratio as a measure of risk
Incidence
rate ratio
Reference Study design Environmental exposure (95% CI)
Adults
Cox-Ganser et al [10] Cross-sectional study with information on Office building with water damage 7.5 (no CI)
dates of hire and asthma diagnosis and mold contamination based
(mean age 46 years) on building inspection
SAHAKIAN
White et al [11] Cross-sectional study with information on School building with evidence of water 8.5 (no CI)
dates of hire and asthma diagnosis damage and mold contamination
(mean age 48 years) based on building inspection
et al
Children
Jaakkola et al [14]a Population-based cohort study with Reported mold odor in the homeb 2.4 (1.1–5.6)
a 6-year follow-up period (1–7 years Reported visible mold in the homeb 0.6 (0.2–1.7)
old at baseline) Reported moisture on surfaces 0.9 (0.5–1.5)
in the homeb
Reported water damage in the homeb 1.0 (0.4–2.3)
Any of above dampness indicators 1.0 (0.7–1.5)
a
Cited in Fisk WJ, Lei-Gomez Q, Mendell MJ. Meta-analyses of the associations of respiratory health effects with dampness and mold in homes. Indoor
Air 2007;17:284–96.
b
Present during the past year at time of initial survey.
DAMPNESS AND MOLD IN THE INDOOR ENVIRONMENT 491
Children
A birth cohort study of 4089 Swedish children at 2 months old and 1 and
2 years old found a positive association between damp home environment
and asthma development 1.74 (95% CI, 1.28–2.39), adjusted for gender, pa-
rental history of allergic disease, socioeconomic status, maternal age, exclu-
sive breastfeeding, maternal smoking, pet ownership, and age of building
[12]. Data on damp home environment were taken from the first question-
naire when the children were 2 months old. Asthma was defined as at least
three episodes of wheezing between 3 months and 2 years of age, in combi-
nation with treatment of inhaled glucocorticoids or signs of hyperreactivity
without upper-respiratory infection. In a subsequent nested case-control
study of the same birth cohort, 181 children who met the case definition
were compared to 359 age-matched healthy controls [13]. Information on
damp indoor conditions came from the baseline questionnaire and from
home inspections in the first winter season after recruitment into the case-
control study. There were consistent positive associations between indica-
tors of dampness/mold in the home and being a case. A strong finding
was that there was an increasing risk for recurrent wheezing with an increas-
ing number of indicators of dampness found during the home inspections:
one indicator of dampness was associated with an OR of 1.3 (95% CI,
0.8–2.2), whereas having three or more dampness indicators was associated
with an OR of 2.7 (95% CI, 1.3–5.4).
A cohort study of randomly selected children from the Finnish popula-
tion registry used results from a survey at age 1 to 7 years and another sur-
vey 6 years later [14]. Response rates and study numbers for the initial and
subsequent surveys were 80% (n ¼ 2568) and 77% (n ¼ 1984), respectively.
Children were considered exposed if mold odor, visible mold, dampness, or
water damage had been reported in the home prior to the baseline study.
The IRR for asthma comparing children exposed (n ¼ 384) and nonexposed
492 SAHAKIAN et al
(n ¼ 1532) to mold odor was 2.44 (95% CI, 1.07–5.60) after adjustment for
age, gender, duration of breastfeeding, parental education, single parent,
maternal smoking during pregnancy, environmental tobacco smoke expo-
sure, gas cooking, presence of furry or feathery pets, and type of child
care. One of the major strengths of this study was its prospective study de-
sign, which eliminated over-reporting of pre-existing home mold based on
newly diagnosed asthma and provided evidence for a temporal relationship
between home mold and asthma.
Other Finnish researchers conducted a case-control study of children
newly diagnosed with asthma at the university hospital in Kuopio, Finland
[15]. Cases were defined as children 1 to 7 years of age who had been referred
to the hospital because of two or more attacks of wheezing within the past
year or were newly diagnosed with asthma. Controls who did not have
asthma were randomly drawn from the Finnish population registry and
matched by age, gender, and municipality to cases. Cases and controls
were required to have lived at least 2 years or at least 75% of their lifetime
in their current homes. Participation rates and study numbers for cases and
controls were 98% (n ¼ 121) and 84% (n ¼ 241). Homes were inspected for
evidence of mold odor, visible mold, and water damage. Models adjusted
for parental asthma, paternal education, number of siblings, indoor pets,
and daycare attendance during the first year of life yielded significant results
for water damage in the main living area (OR 2.24; 95% CI, 1.25–4.01) and
visible mold in the main living area (OR 2.59; 95% CI, 1.15–5.85). The study
found a trend for increased risk for newly diagnosed asthma with each ad-
ditional square meter of observed home water damage (OR 1.36; 95% CI,
0.91–2.03).
Adults
A longitudinal study of subjects who participated in the ECRHS in
Melbourne, Australia, followed 360 adults (20 to 45 years old) over
a 2-year period with regard to measured home exposures and the develop-
ment and remission of asthma [19]. The investigators measured dust mite
and cat allergens and ergosterol (the principal sterol in fungal membranes)
in bedroom floor and bed dust samples and culturable fungi from bedroom
air samples at the onset of the study and 2 years later. They found that
494
Table 3
Epidemiologic studies investigating an association between microbial agents and asthma and asthma-like symptoms
Odds ratios
Total Specific Other Fungal
Reference Study design Health outcome fungi fungi fungi biomass Endotoxin Bacteria MVOC
Adults
Matheson [19]a Longitudinal study: Development:
home (20–45 y) Current asthma 1.5 (a) 1.0 (Cla/a) 1.1 (a) 1.1 (Erg/fd) – – –
SAHAKIAN
Asthma attack 1.5 (a) 1.5 (Cla/a) 1.2 (a) 1.0 (Erg/fd) – – –
PD asthma 0.9 (a) 1.0 (a) 1.0 (a) 1.5 (Erg/fd) – – –
Remission:
Current asthma 1.2 (a) 1.1 (Cla/a) 0.9 (a) 1.1 (Erg/bd) – – –
et al
Wheeze 1.0 (a) 1.0 (Cla/a) 1.0 (a) 0.8 (Erg/bd) – – –
BHR 1.0 (a) 1.0 (Cla/a) 0.9 (a) 0.9 (Erg/bd) – – –
Park et al [20]b Case-control study: Post-occupancy 1.6 (fd) 2.2 (Hyd/fd) 0.7 (fd) 1.4 (Erg/fd) 1.4 (fd) – –
office (mean age 46 y) PD asthma 1.7 (cd) 1.9 (Hyd/cd) 1.3 (cd) 1.6 (Erg/cd) 1.2 (cd) – –
PD asthma or 1.7 (fd) 1.8 (Hyd/fd) 1.1 (fd) 1.6 (Erg/fd) 1.5 (fd) – –
asthma symptoms 1.6 (cd) 1.6 (Hyd/cd) 1.3 (cd) 1.5 (Erg/cd) 1.1 (cd)
Park et al [21]c Cross sectional study: WR wheeze 2.0 (fd) d d d 2.5 (fd) – –
office (mean age 46 y) WR chest-tightness 1.9 (fd) d d d 2.2 (fd) – –
WR shortness 2.4 (fd) d d d 1.9 (fd) – –
of breath
WR cough 1.7 (fd) d d d 1.3 (fd) – –
c
Salo et al [22] Cross sectional study: Current PD asthma – 1.7 (Alt/sd) – – – – –
home (73% O18 y)
Children
Douwes Birth cohort study: PD asthma by age 4 d d d 0.4 (EPS/fd) 0.4 (fd) d d
et al [26]d home (1–4 y) 0.7 (Glu/fd)
Persistent wheeze d d d 0.4 (EPS/fd) 0.7 (fd) d d
in past 4 years 0.4 (Glu/fd)
Hyvärinen Case-control study: Development d 1.1 (Mes/hd) d 1.1 (Erg/hd) 0.7 (hd) 1.2 (Mes, Act/hd) d
et al [27]e home (1–7 y) of asthma 1.1 (Xer/hd) 1.0 (Mes/hd)
van Strien Cross-sectional study: PD asthma 1.1 (Mur/bd)
495
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