Factores Ambientales y el Asma en Hispanoamérica

Factores Ambientales y el Asma en Hispanoamérica Juan C. Celedón, M.D., Dr.P.H.

Channing Laboratory Division of Pulmonary and Critical Care Medicine Department of Medicine Brigham and Women’s Hospital Department of Medicine Harvard Medical School BRIGHAM AND WOMEN’S HOSPITAL

HARVARD MEDICAL SCHOOL

Outline • 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

1.

Asthma in Hispanic America

Demographic and Health Care Characteristics of Hispanic Countries Country

Argentina

Per Capita GDP (Dollars) $12,400

Infant Health Asthma Mortality Spending Deaths Rate 15.18 $238

Colombia

$6,600

20.97

$151

13.44

Costa Rica $9,600

9.95

$383

10.10

Peru

31.94

$93

7.55

$5,600

Puerto Rico $17,700

8.24

37.19

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

Asthma Symptoms, ISAAC I Country

Current wheeze

>=4 attacks

Ever asthma

N

Argentina

16.4%

3.8%

5.3%

6,012

Costa Rica

32.1%

7.3%

26.9%

2,942

Mexico 8.6% (Cuernavaca) Chile 17.9%

1.3%

5.1%

3,097

2.9%

12.1%

10,838

Uruguay 18.0% (Montevideo)

4.6%

12.0%

3,071

Hunninghake GM, Weiss ST, Celed贸n 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.

2.

Potential Risk Factors for Asthma in Hispanic America

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 and Asthma in Hispanic America • 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)

Allergen Exposure 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

Ascaris lumbricoides

www.altcancer.com

Intensity of Parasitic Infection and Asthma in Hispanic America • Inverse association between helminthiasis (active and chronic) and intensity of helminthic infection and atopy in rural Ecuador • Conflicting findings with regard to asthma – Inverse association between helminthiasis and exercise-induced wheeze in Ecuador

Table 1. Characteristics of Participating Children with Asthma in Costa Rica Categorical Variables Sensitized to Ascaris lumbricoides P value for comparison* Number, percentage Yes (n=171) No (n=268) Sex (male)

119 (69.6)

157 (58.6)

0.02

Parental education † Less than High School

87 (50.9)

117 (43.7)

0.33

Skin test reactivity to 1 allergen

162 (95.3)

213 (79.8)

<0.001

Airway responsiveness to methacholine 1.98 mol

107 (70.4)

144 (58.3)

0.02

Bronchodilator responsiveness ‡

32 (19.1)

21 (8.3)

0.002

Hospitalized for asthma, last year

13 (7.6)

9 (3.4)

0.07

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

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

Odds ratio (95% confidence interval), p value Unadjusted Adjusted*

Skin test reactivity to 1 allergen

5.13 (2.38-11.09), <0.001 5.15 (2.36-11.21), <0.001

Airway responsiveness to 1.98 mol of methacholine†

1.70 (1.11-2.62), 0.02

1.61 (1.02-2.54), 0.04

Bronchodilator responsiveness 2.60 (1.44-4.69), 0.002

2.60 (1.34-5.05), 0.005

Hospitalizations for asthma in the previous year§

3.08 (1.23-7.68), 0.02

2.37 (0.99-5.67), 0.05

* 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

Table 3. Sensitization to A. lumbricoides and Continuous Measures of Allergy, Asthma Morbidity and Asthma Severity in Costa Rican Children Outcomes Coefficient estimate (95% confidence interval), p value Unadjusted

Adjusted*

Total IgE (IU/ml)†

0.58 (0.47-0.69), <0.001

0.57 (0.46-0.68), <0.001

Eosinophil count (cells/m3)†

0.18 (0.12-0.25), <0.001

0.20 (0.13-0.26), <0.001

Baseline FEV1 (Liters)§

0.05 (-0.04-0.14), 0.28

-0.06 (-0.12 to -0.01), 0.02

Dose-response slope to methacholine ( mol)†

0.15 (0.04-0.26), 0.006

0.15 (0.04-0.25), 0.009

* 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.

Sensitization to Ascaris and Increased Asthma Severity in Costa Rica • 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

3.

Future Directions

Future Directions • 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

Collaborators • Channing Laboratory, Brigham and Women’s Hospital (Boston, MA): Jody Senter, Barbara Klanderman, Matt Hunninghake, Ngoc Ly, Catherine Liang, Dan Laskey, Ed Silverman, and Scott T. Weiss • Hospital Nacional de Niños (San José, Costa Rica): Manuel Soto-Quiros and Lydiana Avila