Asma

503

Braz J Med Biol Res 37(4) 2004

Cockroach infestation and asthmaBrazilian Journal of Medical and Biological Research (2004) 37: 503-510ISSN 0100-879X

There are more asthmatics in homeswith high cockroach infestation

1Centro de Pesquisas em Alergia e Imunologia Clínica em Pediatria, and2Departamento de Pediatria, Hospital de Clínicas, Faculdade de Medicina,Universidade Federal de Pernambuco, Recife, PE, Brasil

E. Sarinho1,2, D. Schor2,M.A. Veloso2 and

J.A. Rizzo1,2

Abstract

Although asthma has been commonly associated with sensitivity tocockroaches, a clear causal relationship between asthma, allergy tocockroaches and exposure levels has not been extensively investi-gated. The objective of the present study was to determine whetherasthma occurs more frequently in children living in homes with highcockroach infestation. The intensity of household infestation wasassessed by the number of dead insects after professional pesticideapplication. Children living in these houses in the metropolitan area ofRecife, PE, were diagnosed as having asthma by means of a question-naire based on the ISAAC study. All children had physician-diag-nosed asthma and at least one acute exacerbation in the past year.Children of both sexes aged 4 to 12 years who had been living in thehouseholds for more than 2 years participated in this transverse studyand had a good socioeconomic status. In the 172 houses studied, 79children were considered to have been exposed to cockroaches and 93not to have been exposed. Children living in residences with more than5 dead cockroaches after pesticide application were considered to beat high infestation exposure. Asthma was diagnosed by the question-naire in 31.6% (25/79) of the exposed group and in 11.8% (11/93) ofthe non-exposed group (P = 0.001), with a prevalence ratio of 3.45(95%CI, 1.48-8.20). The present results indicate that exposure tocockroaches was significantly associated with asthma among thechildren studied and can be considered a risk factor for the disease.Blattella germanica and Periplaneta americana were the speciesfound in 96% of the infested houses.

CorrespondenceE. Sarinho

Av. Parnamirim, 327, Apto. 202

52060-000 Recife, PE

Brasil

Fax: +55-81-3441-4801

E-mail: [email protected]

Received November 22, 2002

Accepted January 5, 2004

Key words• Cockroaches• Asthma• Atopy• Public health• Plague control

Introduction

Asthma is the most common childhoodillness and is responsible for more than350,000 hospital admissions annually, cor-responding to the 4th most common causefor hospitalization in the Brazilian PublicHealth System (2.3% of the total) and the 3rd

most common among children and youngadults (1).

A multicenter study (International Studyfor Asthma and Allergies in Childhood,ISAAC) carried out in 56 countries demon-strated that the prevalence of asthma hasbeen increasing throughout the world, withBrazil occupying 8th place, with a preva-

504


E. Sarinho et al.

lence of about 20% (2).Mortality rates for asthma are low, but

are increasing in magnitude in a number ofcountries and regions. Mortality rates in de-veloping countries have been rising in thelast ten years, corresponding to 5-10% ofdeaths by respiratory failure, with an el-evated proportion of in-home deaths (1).

The traditional concept of asthma de-fines it as a complex syndrome characterizedby a variable degree of obstruction of airflow, bronchial hyper-responsiveness andinflammation of the lungs as the result ofgenetic and environmental factors (3). It of-ten begins in early childhood and is associ-ated with atopy, a genetically determinedpredisposition toward producing IgE anti-bodies against common environmental aller-gens (4).

Exposure to allergens is assumed to playan important role in asthma, as indicated bythe following considerations: the associa-tion of asthma with sensitivity to commonallergens in the home is strong and found invarious parts of the world; an allergenicbronchial provocation induces both immedi-ate and delayed bronchial responses in asth-matics; a decrease in the levels of exposureto allergens results in a reduction in bron-chial hyperactivity (5).

Sensitivity to mites in household dust isconsidered to be the strongest risk factor forasthma in some studies (6), but other aller-gens have also been demonstrated to be sig-nificantly related to asthma, such as dog andcat epithelium, mold spores and cockroaches(7,8).

Allergy to cockroaches has been recog-nized for more than thirty years (9) andstudies carried out throughout the world haveshown an association between asthma andthe development of specific IgE antibodies.In Brazil, the role of cockroach antigens inrespiratory allergies has only been studied inthe last 5 years (10,11). Various antigensfrom the two most common species in theWestern World, Periplaneta americana and

Blattella germanica, have been identifiedand purified. The most important of theseare the major and the secondary antigenfrom Blattella germanica (Bla g1 and Blag2) and the major antigen from Periplanetaamericana (Per a1), with an extensive cross-reaction between them. Prick test reactivityand blood IgE response to roach antigens aredemonstrable in many asthmatics. It has alsobeen shown that an increase in lymphocyteproliferation in response to Bla g2 antigensis associated with high levels of Bla g1 orBla g2 in homes (11).

A study carried out in 2002 at the Hospi-tal das Clínicas of the Federal University ofPernambuco, demonstrated that allergic sen-sitivity to cockroaches was associated withasthma on the basis of both skin tests andspecific serum IgE. These data suggest thatexposure to insects is a possible risk factorfor the illness (12).

Although the combination of cockroachallergy and exposure to high levels of infes-tation can explain some aspects of asthmaamong these patients, a clear causal relation-ship between these factors has not been suf-ficiently demonstrated (13,14) and more in-formation should be obtained about this re-lationship.

The objective of the present study was todetermine if asthma occurs more frequentlyamong children living in houses with highcockroach infestation and to identify thespecies of cockroaches most frequently foundin the households studied.

Material and Methods

Study design

A cross-sectional study was carried outbetween September 2001 and July 2002 inresidences with and without cockroach in-festations and the presence of asthmatic andnon-asthmatic children in these homes wasalso determined. The Ethics Committee ofthe Hospital das Clínicas of the Federal Uni-

505


Cockroach infestation and asthma

versity of Pernambuco reviewed and ap-proved the protocol and the adults respon-sible for the children who participated in thestudy signed an informed consent form.

Study population

The study population consisted of chil-dren from residences within the metropoli-tan area of the city of Recife, PE, Brazil,whose parents or guardians had hired pro-fessional cockroach extermination services.The company serves 40% of the area marketand accepted the invitation to participate inthis study.

Based on the literature on exposure tocockroaches (12) and the asthma prevalencein the city (2), considering a discriminatorypower of 80% between the two groups, withthe level of significance set at 5% and arelative risk of the occurrence of an asthmaepisode to be 9.22 among those exposed(15), the minimum sample size for an asso-ciation between exposure to cockroachesand asthma was calculated to be 108 chil-dren, 54 of them exposed to cockroaches and54 not exposed.

Inclusion criteria were: age between 4and 12 years, having lived in the residencefor more than 2 years, and absence of diag-nosed heart or respiratory diseases known byparents or guardians.

Children were excluded from the study ifparents or guardians did not give consent toparticipate and also when the pest controltechnician observed visible molds on thewalls or ceiling of the residence, in order toreduce the confounding effect of a probablehigh exposure to mold antigens or high hu-midity.

Procedures

An initial questionnaire was sent to eachresidence that solicited extermination ser-vices for cockroaches. We determined thepresence of children in the household, their

ages and if they had lived there for more thantwo years. A professional pest-control tech-nician from the insect exterminating com-pany, having previously been trained by twomembers of the research team, submitted thequestionnaire to the parents or guardians. Atthat time, the technician verified the extentof cockroach infestation, as well as the spe-cies found, after application of the pesticide.

The extent of cockroach infestation wasdetermined on the basis of direct evidenceaccording to the semiquantitative criteriaestablished by the extermination company,considering the number of cockroaches thatdied after the service: 0 to 5 - little or noinfestation; 6 to 12 - moderate infestation,and more than 12 - high infestation. Thiscriterion is an empirical and tentative onesince there are no data about the correlationof the number of cockroaches in a housewith the burden of antigen present.

The residences willing to participate inthe study were selected from the data sup-plied by the questionnaires in chronologicalorder of entry, according to the previouslyestablished inclusion criteria. Their inclu-sion was based on the solicitation of theinsect exterminating service and not on thecompany files and those that requested theservice more than once a year were excluded.

All the residences were middle/upper-class and presented a homogeneous patternof hygiene. For each residence, only onechild was selected. When more than onechild lived in the house, the youngest withinthe age range of 4 to 12 years who had livedthere for more than 2 years was selected.This was done because the influence of theenvironment seems to be more important asa determinant factor for asthma amongyounger children, when the immune systemis still developing.

The insecticide was a deltametrine prepa-ration applied in gel or liquid form that leavesno volatile residues. A Medline review ofpapers published during the last ten yearsshowed no reports of association of this

506


E. Sarinho et al.

product with asthma. Indeed, the same prod-uct has been used for years for topical treat-ment of pediculosis and scabies in children,even in those with asthma.

Once the residences were selected, amember of the research team, blind to theresults of infestation, applied a new ques-tionnaire to the parents or guardians by tele-phone. The objective of this questionnaire,based on the ISAAC study (2), was to estab-lish the diagnosis of asthma. When the diag-nosis was positive, complementary questionswere asked to assess the severity of the ill-ness according to the criteria for asthmaseverity of the II Brazilian Consensus onAsthma Management (16). The specificISAAC questionnaire for rhinitis was notapplied in order to reduce the length of thetelephone interview and thus reduce thechances of error in the answers.

Statistical analysis

The information gathered was coded anddouble entries were made and stored in adata bank constructed using the Epi-Info(version 6.0) statistical software. A descrip-tive analysis was later carried out to deter-mine the frequency of gender and age vari-ables, followed by an analysis to determinepossible associations between asthma andthe levels of exposure to cockroaches. Con-tingency tables were organized. The preva-lence ratio with the 95% confidence intervalwas calculated as done for case-control stud-ies.

For the purposes of statistical analysis,children in whose houses up to 5 dead cock-roaches were observed after insecticide ap-plication were considered to be non-exposed,and children in whose houses more than 5dead cockroaches were found after insecti-cide application were considered to be ex-posed to high infestation. This cut-off waschosen empirically once it was possible toidentify a group of houses with less than thisnumber of dead insects after extermination

and another group with higher number ofdead insects, usually more than 50, after theinsecticide application.

Results

A total of 181 children whose residenceswere submitted to cockroach exterminationwere eligible for the study. All were frommiddle or high social class families. Nine ofthe responsible adults chose not to partici-pate. Of the 172 subjects who answered theISAAC questionnaire, 45.9% (79/172) wereexposed to high or moderate cockroach in-festation (exposed group) and 54.1% (93/172) were not exposed (non-exposed group).

Of the exposed children, 37 were malesand 42 were females; 45.6% (36/79) were 5years of age or younger and 54.4% (43/79)were older than 5 years. Of the non-exposedchildren, 45 were males and 48 were fe-males; 40.8% (38/93) were 5 years of age oryounger and 59.2% (55/93) were older than5 years. We initially stratified the children byage groups, i.e., older than 5 years and 5years or younger, because children youngerthan 5 years are more subject to asthmaticepisodes, mainly due to viral infections.However, analysis of the results revealed nostatistically significant difference betweenthe two age groups and age stratification wasdiscontinued. There was also no statisticallysignificant difference between genders.

Among the exposed children, 31.6% (25/79) were asthmatic while in the non-exposedchildren only 11.8% (11/93) were asthmatic(prevalence ratio: 3.45; 95%CI: 1.48-8.20),as shown in Table 1. Therefore, the exposedchildren living in homes with high cock-roach infestation had asthma more frequentlythan non-exposed ones, with a statisticallysignificant difference (P < 0.001).

Although the number of patients wassmall for comparison, we found that amongthe exposed children, 64% (16/25) had mildasthma and 36% (9/25) moderate or severeasthma. Among those who were not exposed,

507



72.7% (8/11) had mild asthma and 27.3% (3/11) moderate to severe asthma (P = 0.89). Itwas not possible to correlate the extent ofinfestation with the severity of the diseasedue to the small number of subjects.

Regarding the species found, we observedan infestation by Blattella germanica in55.7% (44/79) of the residences, by Periplan-eta americana in 26.6% (21/79), by Blattellagermanica and Periplaneta americana to-gether in 13.9% (11/79), and by Blattellaorientalis in 3.8% (3/79). Regarding infesta-tion, it is worth mentioning that in non-infested houses, usually no or up to 3 to 5dead insects were observed after insecticideapplication but in those considered to beinfested (more than 5 dead insects) usuallymore than 50 dead insects were observedafter the application. Stratifying the expo-sure to cockroaches according to the originalcompany classification (no/low, medium orhigh infestation) did not change our results.

Discussion

A number of hypotheses have been pro-posed in order to explain the increase inprevalence and morbidity of asthma in de-veloped countries over the last two decades.These hypotheses include changes in lifestylewith individuals spending more time in closedenvironments and a consequent increase inexposure to household allergens (17). Asthmaand other forms of allergic illnesses repre-sent a significant public health problem (18).Cockroaches have been associated withasthma in a number of regions throughoutthe world. Brazilian studies have recentlydemonstrated that 40 to 55% of children andyoung adults with asthma and/or allergicrhinitis exhibit positive reactions to the skintest and/or specific IgE for cockroaches(12,19).

The present study showed that when therewas cockroach home infestation (more than5 dead insects after pesticide), there was alsoa 3.45 higher frequency of asthma in the

children than when there was no cockroachinfestation, in agreement with data of studieswhich used different techniques for the as-sessment of exposure (5,13).

Unfortunately, in contrast to the manycontrolled clinical studies that support theuse of pharmacological treatment of asthma,there has been a relatively small amount ofresearch devoted to the exposure to aller-gens and to the determination of whetherremoving or minimizing allergen exposurewould be an important measure for control-ling asthma (20). Even for dust mites, whichhave been the allergens most extensivelystudied, there is some uncertainty aboutwhether environmental control measureswould actually bring effective benefits to thecontrol of asthma (21).

The population of the present study con-sisted of 172 children of both sexes aged 4 to12 years, from families of fair socioeco-nomic conditions. Exposure is assumed tobe more intense in lower socioeconomicstrata, with a greater association with asthma.Despite the existence of an association be-tween allergic respiratory diseases (includ-ing asthma and rhinitis) and exposure tocockroach antigens; 19), the present groupof children was not investigated for the pres-ence of rhinitis using the ISAAC question-naire.

The household species of cockroachesspend large part of the time aggregated, hid-den in dark and damp places. As a result,

Table 1. Relationship between children exposure to cockroaches within the residenceand prevalence of asthma.

Asthma

Yes No Prevalence ratio (95%CI)

Exposed 25 (31.6%) 54 (68.4%) 3.45 (1.48-8.20)Non-exposed 11 (11.8%) 82 (88.2%) 1Total 36 136

More than 5 dead cockroaches were found in homes of children exposed to cock-roaches after an insect extermination treatment and 5 or less in homes of non-exposed children. 95%CI = 95% confidence interval.

508


E. Sarinho et al.

infestation is not often apparent to the dwell-ers. Gelber et al. (22) demonstrated that 20%of homes studied with no visible evidence ofcockroach infestation exhibited levels of Blag2 in at least one of the rooms of the house.However, the originality of the present re-search lies in the attempt to examine thehypothesis that cockroach infestation by thevisualization and counting of dead insectsafter the application of an insecticide may berelated to the frequency of asthmatic chil-dren living in these houses. The insects leavetheir dens to die after the application of thevenom, permitting an approximate countwhich is a simple way to estimate the extentof infestation that can be of clinical rel-evance. The purpose of the study was not tomeasure the levels of cockroach allergenspresent in the residences, but to quantita-tively assess the presence of cockroaches.However, we realize now that it was anoversight not to have determined the numberof dead cockroaches in each room of thehouse, a procedure that would have permit-ted us to correlate our data with those in theliterature, as mentioned above.

Based on data reported in a study by theNational Cooperative Inner-City AsthmaStudy (NCICAS) in the United States (23),Arruda et al. (14) reported that the combina-tion of exposure and sensitivity to cockroachallergens is a risk factor for the severity ofasthma in children. Analysis of the relation-ship between cockroach infestation and se-verity of the illness in the 36 asthmatic pa-tients in the present study showed that therewere 16 children with mild asthma and 9with moderate and/or severe asthma in theinfested residences, whereas in the residenceswith no infestation 8 children were classi-fied as having mild asthma and just three ashaving moderate and/or severe asthma. Al-though there are studies correlating expo-sure to cockroach allergens with the severityof asthma (14,24), statistical analysis of thepresent data revealed no significant correla-tion between level of infestation and severity

of the illness (P = 0.89). The small number ofasthmatics may explain this result.

The species of cockroaches most com-monly found in homes are Blattella germa-nica and Periplaneta americana (25). Po-tential cockroach allergens in household dustinclude whole bodies of dead insects, saliva,secretions, shed products and feces. Rel-evant allergens have been identified in thebody and the feces of the insects (26), anddifferences in concentration suggest that thefeces are the most important source of aller-gens (27). In the present study, the speciesmost commonly found were Blattella ger-manica (44 homes) and Periplanetaamericana (21 homes), which were bothpresent in some residences (11 homes), fol-lowed by Periplaneta orientalis (3 homes).

The use of professionally applied pesti-cides is effective. However, a long-lastingremoval of cockroaches is difficult. For com-plete extermination, the pesticide must beapplied periodically to all rooms of the house,together with an adequate set of cleaningmeasures in an effort to prevent re-infesta-tion. This would guarantee better control ofthe exposure to allergens, although recentstudies have shown that a significant reduc-tion in the levels of cockroach allergens isdifficult, even when extermination isachieved (28).

There is a lack of knowledge on the partof the population about the relationship be-tween exposure to cockroach allergens andallergic asthma. When questioned, the largemajority of persons interviewed in the pres-ent study (including most parents of asth-matic children) stated that they knew noth-ing about this association.

Cross-sectional studies simultaneouslydescribe the observation of exposure andoutcomes. Consequently, this design cannotbe used to determine a cause and effectrelationship but it is possible to formulatethe hypothesis that the visual presence ofdead cockroaches within residences afterextermination can be associated with a higher

509



frequency of asthmatic children living inthese households. This hypothesis should betested by multivariate analysis in order toeliminate possible confounding factors andby using analytic designs (cohort and case-control studies). In the present study, Blattellagermanica and Periplaneta americana aloneor in combination were the species found in96% of the infested houses, although Blattellaorientalis was observed in 3 (4%) of them.

We recommend further studies on the

subject of exposure to cockroaches in otherregions. We also recommend that parentsand guardians of asthmatic children be alertedto the probable association between cock-roaches and asthma, and, although total long-lasting extermination is difficult, it is worththe effort to minimize infestation as part ofthe strategy of avoiding exposure to aller-gens of asthmatic children and children withrhinitis.

References

1. Consenso Brasileiro no Manejo da Asma, 3 (2002). Jornal dePneumologia, 8: S1-S4.

2. The International Study of Asthma and Allergy in Childhood (ISAAC)(1998). Steering Committee - Worldwide variation in prevalence ofasthma symptoms: The International Study of Asthma and Allergyin Childhood (ISAAC). European Respiratory Journal, 12: 315-355.

3. Busse WW & Lemanske Jr RF (2001). Advances in immunology:asthma. New England Journal of Medicine, 344: 350-362.

4. Larsen GL (1992). Asthma in children. New England Journal ofMedicine, 326: 1540-1545.

5. Platts-Mills TAE, Blumenthal K, Perzanowski M & Woodfolk JA(2000). Determinants of clinical allergic disease. The relevance ofindoor allergens to the increase in asthma. American Journal ofRespiratory and Critical Care Medicine, 162 (Part 2): S128-S133.

6. Squillace SP, Sporik RB & Rakes G (1997). Sensitization to dustmites as a dominant risk factor for asthma among adolescentsliving in central Virginia. Multiple regression analyses of a popula-tion-based study. American Journal of Respiratory and Critical CareMedicine, 156: 1760-1764.

7. Platts-Mills TAE, Rakes G & Heyman PW (2000). The relevance ofallergen exposure to the development of asthma in childhood.Journal of Allergy and Clinical Immunology, 105: S503-S508.

8. Platts-Mills TAE, Vervloet D, Thomas W, Aalberse RC & ChapmanMD (1997). Indoor allergens and asthma: Report of the Third Inter-national Workshop. Journal of Allergy and Clinical Immunology,100: S2-S24.

9. Bernton HS & Brown H (1964) Insect allergy - preliminary studies ofthe cockroach. Journal of Allergy, 35: 506-513.

10. Maia AAM, Croce J, Guimarães JH & Lopes M (1996). Sensibilizaçãoalérgica à Blattella germanica (Insecta: Dyctyoptera) em pacientescom asma e rinite na cidade de São Paulo, Brasil. Revista Brasileirade Alergia e Imunopatologia, 19: 47-50.

11. Filho NAR, Faria L, Riedi CA & Zulato S (1999). Sensibilização abaratas em crianças asmáticas: relação com a gravidade da doença.Revista Brasileira de Alergia e Imunopatologia, 22: 151-155.

12. Lopes MIL (2002). Sensibilização à Blattella germanica e à Periplan-eta americana. Master’s thesis, Universidade Federal de Pernam-buco, Recife, PE, Brazil.

13. Arruda LK, Vailes LD, Platts-Mills TAE, Hayden ML & Chapman MD(1997). Induction of IgE antibody responses by glutathione S trans-ferase from the German cockroach (Blattella germanica). Journal of

Biological Chemistry, 272: 20907-20912.14. Arruda LK, Vailes LD, Ferriani VPL, Santos AB, Pomés A & Chapman

MD (2001). Cockroach allergens and asthma. Journal of Allergy andClinical Immunology, 107: 419-428.

15. Litonjua AA, Carey VJ, Burge HÁ, Weiss TS & Gold DR (2001).Exposure to cockroach allergen in the home is associated withincident doctors-diagnosed asthma and recurrent wheezing. Jour-nal of Allergy and Clinical Immunology, 107: 41-47.

16. Pereira CAC & Sole D (1999). Segundo Consenso Brasileiro noManejo da Asma. Sociedade Brasileira de Pneumologia e Tisiologia,São Paulo, 75-77.

17. Romagnani S (2000). The role of lymphocytes in allergic diseases.Journal of Allergy and Clinical Immunology, 105: 399-408.

18. Call RS, Smith TF, Morris E, Chapman MD & Platts-Mills TAE (1992).Risk factors for asthma in inner city children. Journal of Pediatrics,121: 82-86.

19. Santos AB, Chapman MD, Aalberse RC, Vailes LD, Ferriani VP,Oliver C, Rizzo MC, Naspitz CK & Arruda LK (1999). Cockroachallergens and asthma in Brazil: identification of tropomyosin as amajor allergen with potential cross-reactivity with mite and shrimpsallergens. Journal of Allergy and Clinical Immunology, 104: 329-337.

20. Peyton A & Eggleston PA (2001). Clinical trials of allergen avoidancein established asthma. Journal of Allergy and Clinical Immunology,108: 685-687.

21. Gotzsche PC, Johansen HK, Burr ML & Hammarquist CH (2002).Dust mite control measures for asthma (Cochrane Review). In: TheCochrane Library. Issue 2, Update Software. Oxford, England.

22. Gelber LE, Seltzer LH, Bouzoukis JK, Pollart SM, Chapman MD &Platts-Mills TAE (1993). Sensitization and exposure to indoor aller-gens as risk factors for asthma among patients presenting to hospi-tal. American Review of Respiratory Disease, 147: 573-578.

23. Eggleston PA, Rosenstreich DL, Lynn H et al. (1998). Relationshipof indoor allergen exposure to skin test sensitivity in inner-citychildren with asthma. Journal of Allergy and Clinical Immunology,102: 563-570.

24. Rosenstreich DL, Eggleston PA, Kattan M et al. (1997). The role ofcockroach allergy and exposure to cockroach allergen in causingmorbidity among inner-city children with asthma. New EnglandJournal of Medicine, 336: 1356-1363.

25. National Asthma Education and Prevention Program (1997). ExpertPanel Report 2: Guidelines for the Diagnosis and Management of

510


E. Sarinho et al.

Asthma. NHI Publication, 97-4051. National Heart Lung and BloodInstitute, Bethesda, MD, USA.

26. Musmand JJ, Horner WE, Lopez M & Lehrer SB (1995). Identifica-tion of important allergens in German cockroach extracts by sodiumdodecylsulfate-polyacrylamide gel electrophoresis and Western blotanalysis. Journal of Allergy and Clinical Immunology, 95: 877-885.

27. Yun YY, Ko SH, Park JW, Lee IY, Ree HI & Hong CS (2001).Comparison of allergenic components between German cockroach

whole body and fecal extracts. Annals of Allergy, Asthma, andImmunology, 86: 551-556.

28. Gergen PJ, Mortimer KM, Eggleston PA et al. (1999). Results of theNational Cooperative Inner-City Asthma Study (NCICAS) environ-mental intervention to reduce cockroach allergen exposure in inner-city homes. Journal of Allergy and Clinical Immunology, 103: 501-506.

Documents

Asma