Baltimore Asthma Intervention Trial

Patrick N. Breysse, PhDProfessor and Director Division of Environmental Health

EngineeringDepartment of Environmental Health Sciences

Johns Hopkins Bloomberg School of Public Health

Associate DirectorCenter for Childhood Asthma in the Urban Environment

Centers for Children’s Environmental Health

Co sponsored by NIEHS, EPA, CDC

Johns Hopkins Center for the Asthmatic Child in the Urban

Environment (CCAUE)

Director: Peyton A. Eggleston, MD Associate Director: Patrick Breysse, PhD

Tim Buckley, PhD

Gregory Diette, MD, MS

Sukon Kanchanaraska, PhD

Jerry Krishnan, MD

Elizabeth Matsui, MD

Sekhar Reddy, PhD

Arlene Butz, RN, DSc

Cynthia Rand, PhD

Marsha Wills-Karp, PhD

Steve Georas, MD

Investigators

Why Focus on Asthma?

• In 1999…– 10,488,000 persons with asthma in US (3.8%)– 14.5 million work days lost with asthma– 3,114,000 children < 14 yrs old with asthma (4.9%)– 14 million lost school days– 14.6% report activity limited by asthma– 10,808,000 physician visits– 1,997,000 ER visits for acute asthma– 478,000 hospitalizations for asthma– 4657 deaths

CDC MMWR March 29, 2002 / 51(SS01);1-13

CCAUE

• Multidisciplinary research center

• Combine basic research and community based studies

• Long Term Goals– Understand mechanism by which allergens,

pollutant increases airway inflammation and asthma morbidity

– Develop effective intervention strategies

Environmental Factors in Urban Asthma Research Model

RESPIRATORYMORBIDITY

SUSCEPTIBILITY FACTORSATOPY, INFLAMMATION CONTROL

BRONCHIAL HYPERRESPONSIVENESS

ASTHMATICAIRWAY

OBSTRUCTION

AIR POLLUTANTS

ALLERGENS

CHILDREN LIVINGIN URBAN

ENVIRONMENTS

UNDERLYING SOCIAL SUSCEPTIBILITY FACTORS POVERTY, STRESS, CONFLICTING NEEDS, EDUCATION, ADHERENCE, ACCESS TO CARE

IMMUNOLOGIC SENSITIZATION

CCAUE Study Components

• Community Based Studies– Cohort Study of Environmental Asthma

• Longitudinal comparison of environmental exposures and other risk factors

• Greg Diette et al.

– Asthma Susceptibility to Particulates, Allergens • Genetic association of environmental exposures and asthma• Greg Diette et al.

– Asthma Intervention Trial• Randomized trial to reduced household exposures to

particulate matter and allergens• Peyton Eggleston et al.

CCAUE Study Components

• Basic Biologic Research– Genetics of Response to Ozone

• Mouse model examining genetic basis of Ozone and endotoxin inflammation

• Sekhar Reddy, Steve Kleeberger– Inflammatory Response to Particulate Matter

• Mouse model comparing susceptible and non-susceptible strains

• Compare indoor and outdoor particulate matter• Marsha Wills-Karp

– Dendritic Cell Response to Particulate Matter• In vitro response of cultured dendritic cells• Steve Georas

CCAUE Community Outreach

• Community Advisory Committee– 9 members representing political

organizations, schools, churches, parents

• Advisory Functions– Protocol feasibility– Community priorities, concerns– Translation of results to local community

387 children enrolled in asthma education

program

180 eligible andinterested

13 ineligible 42 refused or unable to contact

125 consented, questionnaire completed

116 baseline home evaluation

100 randomized

97 competed 1 year study

6 refused or unable to contact

16 failed scheduled visits3 moved out of area

3 dropped out of study

93 ineligible44 refused

Recruitment

CCAUE – Asthma Intervention Study

• Randomized Controlled Trial of Home Exposure Control in Asthma

• Rationale– Strong epidemiologic evidence that indoor

environmental exposure relates to asthma morbidity– Effective treatments available for indoor

environmental exposure • Goal

– Test hypothesis that reduction of allergen and pollutant exposure in the homes of asthmatic children will reduce morbidity

STUDY AREA

Air monitoring station

Recruitment Plan

• 100 children recruited from elementary schools in inner city neighborhoods

• Eligibility:

– 6 – 12 years old– Doctor-diagnosed asthma– Current asthma symptoms – No other lung disease – Live in catchment area

Intervention Protocol

questionnaireskin test

serum,FEV1

home environment

telephone

0 3 6 9 12

BASELINE

CONTROL

TREATMENT

TREATMENT

INTERVENTION

Intervention

• 3-4 home visits by home health educators

• Roach extermination, sealed plastic containers

• Allergen-proof bedding encasings

• HEPA air cleaner in child’s bedroom

• Smoking cessation education and support

Air Cleaner

Environmental Monitoring

• Indoor Air Pollutants were measured over a 72-hr period in child's bedroom– Particulate Matter

• PM10

• PM2.5

• Data-logging Nephelometer

– Ozone– Nitrogen Dioxide– Airborne nicotine (marker for passive smoking

exposure)

In-Home Air Sampling Set-Up

0

0.2

0.4

0.6

0.8

1

1.2

1.4 1

6:34

:30

18:

21:3

0

20:

08:3

0

21:

55:3

0

23:

42:3

0

01:

29:3

0

03:

16:3

0

05:

03:3

0

06:

50:3

0

08:

37:3

0

10:

24:3

0

12:

11:3

0

13:

58:3

0

15:

45:3

0

17:

32:3

0

19:

19:3

0

21:

06:3

0

22:

53:3

0

00:

40:3

0

02:

27:3

0

04:

14:3

0

06:

01:3

0

07:

48:3

0

09:

35:3

0

11:

22:3

0

13:

09:3

0

14:

56:3

0

16:

43:3

0

18:

30:3

0

20:

17:3

0

22:

04:3

0

23:

51:3

0

PM

Co

nc

(mg

/m3)

Outdoor

Indoor

Central Site

Comparison of Indoor, Outdoor at the Home, and Outdoor Central Site Particulate Matter

Reservoir Dust Allergen Samples

• Vacuum samples collected in bedroom, living room/family room, and kitchen– Analyzed for

• Cockroach• Dust mite• Cat• Dog• Mouse

Baseline Characteristics

CONTROL TREATMENT

Age (mean) 8.3 8.5

home ETS (%) 65 73

Cockroach (%) 66 62

Pos skin test (%) 65 75

Mod/severe syx (%) 20 28

controller meds (%) 34 28

FEV1 (% pred) 94±21 101±20

ED visit/3 mon (%) 36 32

Housing CharacteristicsCharacteristic % Characteristic %Row House 91 Leaks in bedroom 18

Roof Leaks 24 Food in bedroom 29

Cats 26 Cockroaches in bedroom 8

Dogs 20 Mouse droppings in bedroom

7

Current smoker 46

Moisture damage in kitchen 22

Cockroaches in kitchen 31

Mouse droppings in kitchen 38

0

10

20

30

40

50

60

baseline 6 mon 12 mon

Median Particulate Concentrations

g/m3(median)

PM10 treatment PM 2.5 treatment PM 10 control PM 2.5 control

-50

-40

-30

-20

-10

0

10

20

baseline 6 months 12 months

% c

ha

ng

e f

rom

ba

se

lin

e

PM10 treatment PM 2.5 treatment PM 10 control PM 2.5 control

p<0.001

p<0.001

p=0.08

p=0.019

Particulate Concentrations:% Change

PM10 treatment PM 2.5 treatment PM 10 control PM 2.5 control

Bedroom Cockroach Allergen

1

10

base 6 mon 12 mon

Bla g 1U/gm

p=0.07p=0.001

TreatmentControl

Proportion of children with wheeze, cough, dyspnea in last 2 weeks

-40

-30

-20

-10

0

10

20

30

40

base 3 mon 6 mon 9 mon 12 monCh

ang

e in

pro

po

rtio

n w

ith

sym

pto

ms

Treatment group

Control group

p=<0.001

p=0.60p=<0.001 p=0.02

Other Health Outcomes

• Other health outcomes not different between the two groups– Nighttime symptoms– ED visits– Hospitalizations

– FEV1

Summary

• A global environmental intervention was able to reduce levels of PM10, PM2.5 and cockroach allergen in inner city homes

• There was an associated reduction in symptoms in asthmatic children living in the homes

• Persistence of reduction is uncertain

Acknowledgements

• In addition the investigators previously mentioned– Chris Beck - Nowella Durkin– D’Ann Williams - Mayme Grant– Jean Curtin-Brosnan - Craig Lewis – Lee Swartz - Jennette

Logan– Barry Merriman - Zina Nettles-Smith – Karen Callahan - Dena Scott