Environmental Factors and Asthma: What We Learned from Epidemiological Studies, An Issue of Immunology and Allergy Clinics

201 Pages·2008·2.17 MB·English

by  Mark Eisner

ImmunolAllergyClinNAm
28(2008)xiii–xiv
Foreword
Environmental Factors in Asthma
RafeulAlam,MD,PhD
ConsultingEditor
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
thatenvironmentalchangestriggeredthebiologicalevolution,itisallabout
environment.Weasbiologistshaverecognizedthepowerofgeneseversince
Mendeldemonstratedtheprinciplesofgeneticinheritance,andWatsonand
Crick resolved the structure and beauty of the double helix. The driving
powerofgenesintheexpressionofaphenotypeisundeniable.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
nowunderstandthattheexpressionofageneisfarmorecomplex.Geneex-
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,beingapolygenicdisease,isfarmoresusceptibletoenvironmen-
talchanges.Thus,researchintheenvironmentalaspectofasthmaisveryim-
portant.Acomprehensiveunderstandingoftheenvironmentalcontribution
to asthma requires population-based case control and prospective epidemi-
ologic studies, which areextremely difficultto 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/$-seefrontmatter(cid:2)2008ElsevierInc.Allrightsreserved.
doi:10.1016/j.iac.2008.04.002 immunology.theclinics.com
xiv FOREWORD
indoor pollution. We recognize the complex biologic effect of indoor aller-
gens. To elaborate on the complexity of environmental factors, Dr. Mark
Eisner,aleaderinthefield,hasinvitedsomeofthetopexpertstocontribute
to this issue. The issue addresses such important areas as indoor allergens,
indoorandoutdoorpollution,hygienehypothesisdealingwithmicrobialen-
vironment, social environment that includes diet and obesity, and others.
This will be an exciting reading.
Rafeul Alam, MD, PhD
Division of Allergy and Immunology
National Jewish Medical and Research Center
University of Colorado at Denver Health Sciences Center
1400 Jackson Street
Denver, CO 80206, USA
E-mail address: [email protected]
ImmunolAllergyClinNAm
28(2008)xv–xvi
Preface
MarkD.Eisner,MD,MPH
GuestEditor
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
thedramaticincreasesinasthmaprevalenceandseverity.Dramaticchanges
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
outdoorenvironmentaredramaticfeaturesofthetwentiethandtwenty-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-
flectsallthatisexternaltothehumanorganism.Formany,theterm‘‘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
othersubstances,thereareuniquepointsourcesofpollution,allergenexpo-
sure,andviralinfectionindoors.Andfinally,thesocialenvironment,which
0889-8561/08/$-seefrontmatter(cid:2)2008ElsevierInc.Allrightsreserved.
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.
Randomizedcontrolledtrialshavebecomethegoldstandardforaddress-
ing many problems in clinical medicine and health. But such trials are not
suitedtostudyingmostoftheeffectsofenvironmentalexposuresonhealth.
Althoughshort-termexposurestudiesareconductedinhighlycontrolleden-
vironments, they provide limited insight into the development of chronic
diseases such as asthma, which have a long induction period (ie, develop
overalongperiodoftime). Ethical and logisticconcerns preclude random-
izing humansubjectstopotentially hazardousexposures overalongertime
period.Therefore,epidemiologicmethodsarethebestonesforassessingthe
impactofenvironmentalexposuresonhealthoutcomes,suchasasthmaand
other respiratory diseases.
In this issue, we review the evidence that exposures to indoor pollution
(passive smoking, indoor combustion), other indoor exposures (allergens,
viralinfections,occupationalexposures,dampness,mold),andoutdoorpol-
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
afarm,withexposuretomicrobesandallergens,hasfascinating,andsome-
times counterintuitive, effects on asthma induction and course. Finally, an
articleonasthmaandtheinnercityintegratestheissuesofpollutantandal-
lergen exposure that often occur concurrently in the urban environment.
Ultimately,thegoalofepidemiologyandpublichealthispreventiondin
thiscase,preventionofasthmaincidenceandexacerbation.Thisissueeluci-
dates the impact of the environment, defined broadly, on asthma with the
goalofhighlighting possibleareas inwhichexposureprevention or remedi-
ation might decrease the burden of asthma.
Mark D. Eisner, MD, MPH
University of California San Francisco
505 Parnassus Avenue, M1097
San Francisco, CA 94143, USA
E-mail address: [email protected]
ImmunolAllergyClinNAm
28(2008)485–505
Dampness and Mold in the Indoor
Environment: Implications for Asthma
N.M. Sahakian, MD, MPH*, J.-H. Park, ScD, CIH,
J.M. Cox-Ganser, PhD
CentersforDiseaseControlandPrevention,NationalInstituteofOccupationalHealth
andSafety,DivisionofRespiratoryDiseaseStudies,1095WillowdaleRoad,
MS-H2800,Morgantown,WV26505,USA
The National Institute for Occupational Safety and Health receives
weekly requests to help with issues of indoor environmental quality in rela-
tion to illness in nonindustrial workplaces, such as office buildings and
schools.Sincethe mid-1990s, there has been a marked increasein the num-
beroftheserequeststothepointwherein2007theyrepresented57%ofthe
total of 390 requests for evaluation of the workplace in relation to health
and safety issues. As an example of requests concerning work-related
asthma,fromJanuary2007throughDecember2007,therewere39requests
inrelationtoasthma,34(87%)fromnonindustrialworkplaceswithworkers
concerned about indoor environmental quality. Of these 34 requests,
23 (68%) listed dampness or mold as exposures of concern. Thus, asthma
in the nonindustrial environment accounts for the majority of the public’s
concern for possible work-related asthma, and requesters have made the
association between their work-related asthma symptoms and damp/moldy
environments. A recent calculation estimates that 21% (95% confidence
interval [CI], 12%–29%) of current asthma in the United States is attribut-
able to dampness/mold in homes [1].
This article presents epidemiologic findings pertinent to asthma and
asthma-like symptoms in relation to exposure to dampness/mold in homes,
schools,andworkplaces.Withregardtospecificagentsfoundindampindoor
environmentsthatmayplayaroleinasthma,itconcentratesonmold(used
synonymouslywithfungi)andincludessomefindingsonbacteria.Thelitera-
tureonasthmainrelationtodustmiteorcockroachallergensisnotaddressed.
Thefindingsandconclusionsinthisreportarethoseoftheauthorsanddonotnecessar-
ilyrepresenttheviewsoftheNationalInstituteforOccupationalSafetyandHealth.
* Correspondingauthor.
E-mailaddress:[email protected](N.M.Sahakian).
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doi:10.1016/j.iac.2008.03.009 immunology.theclinics.com
486 SAHAKIANetal
Reviews of the epidemiologic literature up to 2003
AEuropeanreview(NORDDAMP)ofwell-designedepidemiologicstud-
ies published prior to July 1998 found that odds ratios (ORs) for cough,
wheeze, and asthma associated with indoor dampness ranged from 1.4 to
2.2 [2]. A subsequent review (EUROEXPO) of studies published from
1998 to 2000 confirmed indoor dampness as a risk factor for health effects,
regardlessofatopicstatus.Theinvestigatorsconcludedthatadditionalpro-
spective studies were needed [3].
In the United States, the Centers for Disease Control and Prevention
askedtheInstituteofMedicine(IOM)tocomplete areviewofthescientific
literature. The IOM committee reviewed studies published up to late 2003
believed influential in shaping the scientific understanding of dampness-
associated health effects [4]. With respect to asthma and asthma-related
symptoms,theIOMfoundthattherewassufficientevidenceforassociations
betweenexposuretodamp indoorenvironments ormold orotheragentsin
damp indoor environments and cough, wheeze, and asthma symptoms in
asthmatic persons, and limited or suggestive evidence for associations
with asthma development and dyspnea. They concluded that excessive in-
doordampnessisapublichealthproblemandthatpreventionorreduction
of this condition should be a public health goal. Among the research needs
formulated by the committee were improved characterization of dampness-
relatedmicrobial emissions andchemical emissions from buildingmaterials
andfurnishingsandtheirrolesinadversehealthoutcomes;studiesoninter-
action effects of multiple exposure factors in damp indoor environments;
and studies on intervention effectiveness.
Meta-analysis in 2007
Ameta-analysisof33peer-reviewedepidemiologicstudiesonrespiratory
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.
Dampness/mold and asthma developmentdrecent publications
Recent research not included in the 2004 IOM report has increased the
body of evidence regarding the association between dampness and asthma
development (Tables 1 and 2).
DAMPNESSANDMOLDINTHEINDOORENVIRONMENT 487
Adults
Inastudythatinvestigatedoccupationalexposures,researchersreviewed
medical records at clinics in a Swedish town covering a 1.5-year period to
identifycasesofnewlydiagnosedasthmaamong20to65yearolds[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
3ormoreyearsandoccurredbeforetheyearofasthmadiagnosis(forcases)
orreferenttime(forcontrols)was4.7(95%CI,1.5–14.3).Becausethisstudy
included agricultural and maintenance workers whose exposure may differ
inintensityandtypefromoffice workersindampbuildings,cautionshould
be exercised when applying these findings to workers of nonindustrial in-
door environments.
AstudybyGunnbjo¨rnsdo´ttirandcolleaguesuseddatafromthe1990–1994
European Community Respiratory Health Surveys (ECRHS) and a follow-
up survey conducted in 1999–2001 [7]. Participants from four Nordic coun-
trieswere20to44yearsoldatthetimeoftheinitialsurvey.Responserates
and study numbers for the initial and follow-up surveys were 84% (n ¼
21,802)and74%(n¼16,190).New-onsetasthmawasdefinedasanasthma
attackoruseofasthmamedicationsduringthepast12monthsonthesecond
surveywithnegativeresponsestobothofthesequestionsonthefirstsurvey.
The OR (adjusted for age, study center, gender, body mass index, rhinitis,
smoking status,typeofhousing,ageofbuilding,andsocioeconomicstatus)
fortheassociationbetweenthepresenceofhomedampnessanytimebetween
thetwosurveysandnew-onsetasthmawas1.13(95%CI,0.92–1.40)andthus
didnotquitemeetstatisticalsignificance.Associationsfornew-onsetasthma
symptoms were significant. Researchers also investigated the remission of
asthma-like symptoms and found that presence of home dampness in-
betweenthetwosurveyssignificantlydecreasedremissionofnocturnaldysp-
neaandnocturnalcough.Analysisofasubset(Swedishsubjects,n¼1854)of
second survey, also by Gunnbjo¨rnsdo´ttir and colleagues, participants
demonstrated significant positive associations between home dampness
and dyspneaat 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.
Casesandcontrolswere21to63yearsoldandlivedwithinthesamehospi-
tal district in South Finland. Workplace wall-to-wall carpeting and work-
place mold independently increased the risk for new-onset asthma.
Table1 4
8
Epidemiologicstudiesinvestigatinganassociationbetweenindoordampnessormoldandnew-onsetasthmaornew-onsetasthma-likesymptomsthatuse 8
oddsratiosasameasureofrisk
Reference Studydesign Environmentalexposure Healthoutcome Oddsratio(95%CI)
Adults
Flodinand Longitudinalcase-controlstudy Reportedworkplacedampness New-onsetphysician-diagnosed 4.7(1.5–14.3)
Jo¨nsson[6] (20–65yearsold) (moldormoisturedamage)a asthmaatage20–65years
Gunnbjo¨rnsdo´ttir Prospectivestudywitha7.9-year Reporteddampness(water New-onsetasthmaattack 1.1 (0.9–1.4)
etal[7] follow-upperiod(meanage damage,leakage,ormold orcurrentuseofasthma
atfollowup:40years) growth)inthehomeb medicationsc
New-onsetwheezec 1.3 (1.1–1.5)
New-onsetnocturnaldyspneac 1.3 (1.1–1.6)
New-onsetnocturnalcoughc 1.3 (1.1–1.4) S
A
H
A
K
Jaakkolaetal[9] Population-basedincident Reportedvisiblemoldormold New-onsetphysician-diagnosed IA
case-controlstudy odoratworkcand asthmawithbothreversible N
e
(21–63yearsold) –Nowall-to-wallcarpetatwork airwaysobstructionand 1.4 (0.9–2.1) t
a
–Wall-to-wallcarpetatwork ahistoryofatleastone 4.6 (1.1–19.4) l
asthma-likesymptom
Children
Wickmanetal[12] Prospectivestudyofabirth Reportedwaterdamage, Threeormoreepisodesof 1.7(1.3–2.4)
cohortfromage2months windowpanecondensation, wheezingafterage3months
to2yearsofage visiblemold,ormoldodorwhen andeitheruseofinhaledsteroids
childwas2monthsofage orsymptomssuggestiveof
bronchialhyper-reactivity
Emeniusetal[13] Nestedcase-controlstudyof Onesignofdampnessbased Threeormoreepisodesof 1.3 (0.8–2.2)
abirthcohort(2yearsold) onhomeinspection wheezingafterage3months
Threeormoresignsofdampness andeitheruseofinhaled 2.7 (1.3–5.4)
basedonhomeinspection steroidsorsymptomssuggestive
ofbronchialhyper-reactivity
Pekkanenetal[15] Population-basedincident Moldodorbasedoncurrent New-onsetphysician-diagnosed 4.1 (0.6–26.0)
case-controlstudy homeinspection asthmaornewreferral
(1–7yearsold) Visiblemoldbasedoncurrent tohospitalaftertwoor 1.2 (0.7–2.1)
homeinspection moreattacksofwheezing
Visiblemoldinmainliving 2.6 (1.2–5.8)
areabasedoncurrent
homeinspection
Waterdamageinmainliving 2.2 (1.2–4.0)
areabasedoncurrent D
A
homeinspection M
P
N
a Presentfor3ormoreyearsandoccurredatleast3yearsbeforeyearofasthmadiagnosis. ES
S
b Presentanytimeinbetweentheinitialandfollow-upsurvey. A
N
c Presentduringthepastyear. D
M
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L
D
IN
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H
E
IN
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O
O
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N
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