Environmental Factors
in Pediatric Respiratory Disease
W. Gerald Teague, M.D.
The Emory Asthma Center and
Pediatric Environmental Health Specialty Unit
Emory University School of Medicine
Interaction of Environmental and Genetic
Factors in the Natural History of Asthma
Environmental Exposures:
Allergens, Infections,
Tobacco Smoke
“Triggers”
Normal Lung
Function
Inception of
Asthma
Genetic Factors:
Atopy
Airways Hyperreactivity
Mild
Asthma
Severe
Asthma
Impact of Environmental Factors
on T Lymphocyte Differention
B Cell
Activation
Default Pathway
Undifferentiated T
Helper Cell
IL- 4
Th2 Phenotype
IL- 5
Environmental
Exposures
IL-12
Th1 Phenotype
Eosinophil
Signaling
Environmental Exposures Associated
with Decreased Risk of Asthma
• Crowded living arrangements
• Increased number of siblings
• Exposure to group day care
• Early exposure to dogs
• Rural versus urban environment
• Exposure to farm animals
• Diet high in fish oil
Environmental Exposures Associated
with Increased Risk of Asthma
• Maternal smoking
• Being reared in a dusty home
• Early introduction of non-milk foods in diet
• Antibiotic treatment during infancy
• “Western” life style
Routes of Exposure
• Breathing
- Children at higher risk:
Minute ventilation
newborn 400 ml/min/kg/body weight
adult
150 ml/min/kg/body weight
• Trans-placental
- Exchange of fetal lung fluid with
amniotic fluid
Breathing Zones
Adult
4 ft
1 ft
Infant
Exposure to dust
mite, cock roach,
mercury
Specific Environments
• Prenatal
• Home
• School and day care
• Food and water
• Occupational
• Medical treatments and cosmetics
Evidence that Prenatal Tobacco Smoke
Exposure Increases Risk of Respiratory Disease
• Lung function and histology in the offspring
of exposed pregnant rats
• Increased risk of asthma and reduced
lung function in children born to
mothers who smoke
Environmental Tobacco Smoke
• Prenatal exposure highly correlated with
wheezing during first year of life.
• Maternal smoking of > 1/2 pack per day:
2.5 X increased risk of asthma in children
• Role for ETS as both a trigger for wheezing
and in the inception of asthma.
Effects of In Utero and Environmental Tobacco
Smoke Exposure on Lung Function in Boys with Asthma
2
1
0
% Change
from Unexposed
Reference Group
-1
-2
-3
FVC
FEV1
-4
-5
-6
-7
-8
Past ETS Current In Utero In Utero
ETS
+ ETS
Li et al, Am J Respir Crit Care Med 2000; 162: 2097
Effects of Chronic Alcohol Abuse on Lung
Antioxidant Capacity
800
700
BAL
Glutathione
(umol)
600
500
400
300
200
100
0
Alcoholics
Controls
Moss et al. Am J Respir Crit Care Med 2000; 161:414
Importance of the Home Environment
• Infants and children spend relatively
more time indoors
• Exposure to a wide range of bioallergens, VOC’s, combustion sources
• Modern homes and buildings better
insulated - less air exchange
Asbestos and Radon
Asbestos
• An important cause of lung cancer and malignant
mesothelioma in adults.
• Risk of pulmonary disease is dose-dependent.
• Exposure through inhalation of fibers used in
building materials.
Radon
• Gas from the radioactive decay of uranium deposits
in rocks and soil.
• Exposure associated with increased rates of lung cancer.
Important Indoor Agents
Precipitating Asthma
Agent
Major Sources
Allergens
Dust mite
Animal
Cock roach
Molds
Tobacco smoke
Nitrogen oxides (NO2)
VOC’s
Odors
Carpet, mattresses, pillows
Cats, dogs, rodents
Kitchens, bathrooms
Basements, bathrooms
Cigarettes, pipes, cigars
Indoor combustion
Formaldehyde- pressed wood
Sprays, deodorizers, pesticides
Dust Mite Sensitization and Asthma
• Immune response is to a digestive protein
passed in the mite feces.
• Two major mite antigens der f 1 and der p 1
• High rate of sensitization in children admitted
to the hospital with asthma.
Ecology of the Dust Mite
Dust mite
Exfoliated skin
Asthma
Humid Environment
Bedding
Inflammatory
Response
Inhalation of antigen
Deposition in the
respiratory tract
Avoidance Measures for Dust Mite
• Encase pillows and mattresses in plastic
• Decrease room humidity levels to < 50%
• Wash bedding in hot (> 120° F) water
every two weeks
• Remove carpeting and area rugs
• Enclose stuffed animals, toys, in closets
• Move to high altitude
Cock Roach Antigen and Asthma
• Major public health problem in the inner city
• Levels highest in the kitchen, bathroom, and
TV-watching areas
• 60% of urban residents with asthma are
sensitized
Avoidance Measures for Cock Roach
• Minimize organic materials on open surfaces
• Store foodstuffs in sealed containers
• Restrict eating to the kitchen
• Caulk cracks around faucets and pipes
• Stick traps and boric acid
• Professional extermination - last resort
Cat Antigen (Fel d 1)
• Highly respirable
• Difficult to clear from the environment
• Found in highest concentrations in dander
• Control measures:
- get rid of cat
- scrub cat at intervals
- special HEPA filters on vacuum
Mold and Asthma
• Alternaria and aspergillus main species
• Found in dark, moist environments
- bathrooms, basements, crawl spaces, air
conditioner collecting systems.
• Known trigger for asthma exacerbations
• Controlled by reducing humidity to < 50%
Indoor Sources of Combustion
• Gas stoves, space heaters, wood stoves
• Main species produced include nitrogen
oxides, CO, methane
• Exposure linked to increased respiratory
symptoms
Important Outdoor Agents
Precipitating Asthma
Agent
Major Source
Ozone (O3)
Hydrocarbon combustion
Sulfur Dioxide
Fossil fuels, industry
Particles
Diesel exhaust, wood
Acid aerosols
Southwestern U.S.
Mold spores
Alternaria, Aspergillus
Principal Components of Smog
Pollutant
Air Limit
Averaging Time
Ozone
0.08 ppm
8 hours
PM10
50 µg/m3
150 µg/m3
Annual mean
24 hours
PM2.5
15 µg/m3
Annual mean
65 µg/m3
24 hours
SO2
0.03 ppm
0.14 ppm
Annual mean
24 hours
NO2
0.053 ppm
Annual mean
The London Air Pollution Crisis - 1952
Daytime photo of
Bus, December 6th
Smoke, SO2 Levels,
and Mortality
Importance of Fine Particulate Air Pollution and
Mortality in 20 U.S. Cities 1987-1994
• Pollutants surveyed:
- fine particles < 10 µm in aerodynamic diameter (PM10)
- ozone
- carbon monoxide
- sulfur dioxide
- nitrogen dioxide
• Analysis: two-stage analytic approach of pooled data
• Results
- relative rate of death from cardiovascular and respiratory
illnesses increased 0.68% for each increase in PM10 level
of 10 µg per cubic meter.
Samet et al. N Engl J Med 2000; 343:1742
Ozone Exposure and Asthma:
The Atlanta Experience
• Ground ozone level > EPA standards:
- 33% increase in visits to Grady Hospital for children
with acute wheezing
• Ground ozone levels less than normal:
- 42% decrease in asthma activity around the city
Ozone Avoidance Measures for
Children with Asthma
• Monitor daily smog forecasts May-Sept.
• Limit outdoors activity as much as possible,
especially late in the afternoon
• Close all doors and windows of the house,
use the air conditioner
School and Day Care Exposures
• Air pollution
• Bio-allergens
• Volatile Organic Compounds
Case Presentation
• JH is a 12 y/o female admitted for evaluation of intermittent
chest pain and shortness of breath.
• The symptoms started four weeks before admission and
were most acute while at school, especially at 11:00 a.m
while in band practice. The patient was symptom-free at home.
• Physical examination, EKG, chest film, arrhythmia monitoring,
and an echocardiogram were normal.
• JH diagnosed with an “acute panic disorder” and discharged
on a medication to reduce anxiety.
Pulmonary Evaluation and Treatment
• A treadmill exercise study showed a 16% decrease in FEV1
after exercise.
• Peak flow monitoring showed a consistent fall in PEFR and
chest tightness within one or two hours of attending an early
morning class held in a new trailer.
• Treatment with fluticasone 110 MDI - two puffs BID and
albuterol before entering the trailer completely restored
lung function and resolved the symptoms.
Formaldehyde and Asthma
• Volatile organic compound emitted as a gas
from laminated wood products (particle board).
• Formaldehyde is a respiratory irritant and can
trigger exacerbations of asthma.
• Exposure risk highest in new modular buildings
with pressed wood construction.
Smedje G et al. Asthma among secondary school children in relation
to the school environment. Clin Exp Allergy 1997; 27 :1270-78.
The “Sick” Building Syndrome
• Work-related nasal discharge, cough,
wheezing, and migraine headache.
• Symptoms more common in workers
exposed to modern offices with heatventilating air conditioning units (HVAC)
and fan coil units (FCU).
Vincent et al, Envir Res 1997; 75:100.
Typical Modern “HVAC” System
The School Environment
• Assessment of bio-allergen levels in 52
public schools near Birmingham, AL.
• > 25% classrooms had levels of dust mite
exceeding threshold sensitization levels.
• > 25% cafeteria rooms had levels of cock
roach exceeding threshold sensitization
levels.
Turner-Henson et al, AJRCCM 2000; 161:A619
Food and Water Exposures
• Dietary factors may accelerate the inception
of asthma by affecting T cell differention.
• Certain foods may act as allergens and trigger
asthma exacerbations:
- shell fish
- milk products
- peanuts
Occupational Exposures
• Volatile organic compounds and respiratory irritants:
- cleaning agents - restaurants, nursing homes, schools
- isocyanates - auto body repair, roofing
- wood dusts - shops, furniture making
• Asbestos
- auto brake repair, renovation projects
• Tobacco smoke
- restaurants
Extrinsic Allergic Alveolitis
An abnormal immunologic reaction in the lung to
antigens contained in a variety of organic dusts.
• Thermophilic bacteria - Farmer’s lung
• Avian proteins - Bird fancier’s lung
• Thermophilic fungi - Mushroom
workers lung, bagassosis (sugar cane),
moldy malt
9 y/o with interstitial pattern and avian
hypersensitivity pneumonitis
Respiratory Diseases Associated with
Inhalation of Inorganic Dusts (Pneumoconiosis)
The accumulation of dust in the lungs and the
tissue reaction to its presence.
•
•
•
•
27 y/o sandblaster with apical nodular
opacities and enlarged hilar lymph nodes
Silicosis - sandblasters
Coal and carbon workers
Asbestos
Beryllium - refinery workers
Medical Treatments
Ionizing radiation
• Interstitial fibrosis following thoracic irradiation
Drug-induced lung disease
• Chemotherapy - bleomycin, busulfan
• Anti-metabolites - methotrexate
• Anti-microbials - nitrofurantoin, sulfasalazine
• Anti-arrhythmics - amiodarone
• Anti-convulsants - diphenylhydantoin
Controversial Environmental
Control Measures
• Acaricides
• Custom heating/air ventilation systems
• Filters
• Humidifiers
• Chihuahua dogs
• Air purifiers/ozone generators