FactoresFactores AmbientalesAmbientales y el y el AsmaAsma en en HispanoamHispanoamééricaricaJuan C. CeledJuan C. Celedóón, M.D., Dr.P.H.n, M.D., Dr.P.H.Channing Laboratory Division of Pulmonary and Critical Care MedicineDepartment of MedicineBrigham and Women’s HospitalDepartment of MedicineHarvard Medical School

BRIGHAM AND WOMEN’S HOSPITAL

HARVARDMEDICAL SCHOOL

• Asthma in Hispanic America• Potential Risk Factors for Asthma in Hispanic

America– Air pollution– Passive exposure to smoking – Obesity– Allergen exposure– Intensity of Parasitic Infection

Outline

Asthma in Hispanic America

1.

Demographic and Health Care Characteristics of Hispanic Countries

37.198.24$17,700Puerto Rico

7.55$9331.94$5,600Peru

10.10$3839.95$9,600Costa Rica

13.44$15120.97$6,600Colombia

$23815.18$12,400Argentina

Asthma Deaths

Health Spending

Infant MortalityRate

Per Capita GDP (Dollars)

Country

Hunninghake GM, Weiss ST, Celedón JC. Am J Respir Crit Care Med 2006; 173:143-63.

Asthma Symptoms, ISAAC I

3,07112.0%4.6%18.0%Uruguay (Montevideo)

10,83812.1%2.9%17.9%Chile

3,0975.1%1.3%8.6%Mexico (Cuernavaca)

2,94226.9%7.3%32.1%Costa Rica

6,0125.3%3.8%16.4%Argentina

NEver asthma

>=4 attacks

Current wheeze

Country

Hunninghake GM, Weiss ST, Celedón JC. Am J Respir Crit Care Med 2006; 173:143-63.

Asthma in Hispanic America

• Asthma is a major cause of morbidity in Hispanic America

• There is marked variation in asthma prevalence among and within Hispanic American countries– Likely due to genetic and environmental

factors

Hunninghake GM, Weiss ST, Celedón JC. State of the Art: Asthma in Hispanics. Am J Respir Crit Care Med 2006; 173:143-163.

Potential Risk Factors for Asthma in Hispanic America

2.

Air Pollution

• Associated with asthma morbidity in non-Hispanic populations

• Mexico City– Exposure to ozone and particulate matter

has been associated with• Reduced lung function• Urgent visits and school absences due to

asthma

Air Pollution and Asthma in Hispanic America

• Previous studies limited by– Cross-sectional or ecologic design– Small sample size– Non-assessment of individual exposures– Non-assessment of other risk factors for

asthma morbidity (e.g., allergens)– Limited data on asthma per se

Passive Smoking Exposure and Asthma in Hispanic America• Few studies

– In utero smoking associated with increased risk of asthma in Costa Rica (Celedón JC, et al. Chest 2001)

– ETS exposure in infancy associated with current wheeze in Ciudad Juárez (Rojas N, Rev Alerg Mex 2001)

• Limited by– Cross-sectional design– Small sample size– No objective measurements of exposure

• Obesity is common in Hispanic America, particularly in urban areas

• Studies in adults (cross-sectional)– Obesity was associated with a twofold

increase in asthma risk in Mexican men and women (Santillan A, et al. Int J Obes Rel Metab Disord 2003)

– Obesity was associated with increased risk of wheeze in Chilean women (Bustos P, et al. Int J Obes Rel Metab Disord 2005)

Obesity and Asthma in Hispanic America

• Exposure to high levels of dust mite allergen is common, particularly in coastal and/or tropical areas

• Few studies have examined allergens other than dust mite– High levels of cockroach allergen in Costa

Rica, specially in coastal areas

Allergen Exposure and Asthma in Hispanic America

• There have been no longitudinal studies of allergen exposure in early life and asthma in Hispanic America

Allergen Exposure and Asthma in Hispanic America

www.altcancer.comwww.altcancer.com

AscarisAscaris lumbricoideslumbricoides

• Inverse association between helminthiasis (active and chronic) and intensity of helminthic infection and atopyin rural Ecuador

• Conflicting findings with regard to asthma– Inverse association between helminthiasis

and exercise-induced wheeze in Ecuador

Intensity of Parasitic Infection and Asthma in Hispanic America

0.079 (3.4)13 (7.6)Hospitalized for asthma, last year

0.00221 (8.3)32 (19.1)Bronchodilator responsiveness ‡

0.02144 (58.3)107 (70.4)Airway responsiveness to methacholine � 1.98 �mol

<0.001213 (79.8)162 (95.3)Skin test reactivity to �1 allergen

0.33117 (43.7)87 (50.9)Less than High SchoolParental education †

0.02157 (58.6)119 (69.6)Sex (male)

No (n=268)Yes (n=171)Number, percentage

P value for comparison*

Sensitized to Ascaris lumbricoidesCategorical VariablesTable 1. Characteristics of Participating Children with Asthma in Costa Rica

* ‡ An increase of at least 200 ml and at least 12% in FEV1 after administration of albuterol.

3.08 (1.23-7.68), 0.022.37 (0.99-5.67), 0.05Hospitalizations for asthma in the previous year§

2.60 (1.34-5.05), 0.0052.60 (1.44-4.69), 0.002Bronchodilator responsiveness

1.61 (1.02-2.54), 0.041.70 (1.11-2.62), 0.02Airway responsiveness to � 1.98 �mol of methacholine†

5.15 (2.36-11.21), <0.0015.13 (2.38-11.09), <0.001Skin test reactivityto �1 allergen

Adjusted*UnadjustedOdds ratio (95% confidence interval), p valueOutcomes

Table 2: Sensitization to A. lumbricoides and Categorical Measures of Allergy, Asthma Morbidity, and Asthma Severity in Costa Rican Children

* All multivariate models are adjusted for age, gender, and parental education level. Multivariate models for airway responsiveness and bronchodilator responsiveness are additionally adjusted for height and FEV1.† Also adjusted for paternal asthma history.§ Also adjusted for use of anti-inflammatory medications

0.15 (0.04-0.25), 0.0090.15 (0.04-0.26), 0.006Dose-response slope to methacholine (�mol)†

-0.06 (-0.12 to -0.01), 0.020.05 (-0.04-0.14), 0.28Baseline FEV1 (Liters)§

0.20 (0.13-0.26), <0.0010.18 (0.12-0.25), <0.001Eosinophil count (cells/m3)†

0.57 (0.46-0.68), <0.0010.58 (0.47-0.69), <0.001Total IgE (IU/ml)†

Adjusted*Unadjusted

Coefficient estimate (95% confidence interval), p valueOutcomes

Table 3. Sensitization to A. lumbricoides and Continuous Measures of Allergy, Asthma Morbidity and Asthma Severity in Costa Rican Children

* All models were adjusted for age, gender, and parental education level. Models for FEV1, FEV1/FVC, airway responsiveness, and bronchodilator responsiveness were additionally adjusted for height. In addition, models for airway responsiveness and bronchodilator responsiveness were adjusted for baseline FEV1.† Variable was log10 –transformed prior to analysis.§ Also adjusted for number of children sharing the bedroom.

• Likely explanations– Children with severe atopy and asthma

have enhanced immune responses against Ascaris lumbricoides

– Removal of immuno-regulatory influences of helminthes by previous antihelminthic treatment

Sensitization to Ascaris and Increased Asthma Severity in Costa Rica

Future Directions

3.

• Case-control studies of modifiable risk factors– ETS exposure, obesity, access to health care– Unique risk factors: indoor exposure to wood smoke,

community violence

• Longitudinal studies/clinical trials– Helminthiasis and atopy/asthma– Air pollution, allergen exposure, obesity

Future Directions

• Channing Laboratory, Brigham and Women’s Hospital(Boston, MA): Jody Senter, Barbara Klanderman, Matt Hunninghake, Ngoc Ly, Catherine Liang, Dan Laskey, Ed Silverman, andScott T. Weiss

• Hospital Nacional de Niños (San José, Costa Rica): Manuel Soto-Quiros and Lydiana Avila

Collaborators