Environmental Factorsin Pediatric Respiratory DiseaseW. Gerald Teague, M.D.The Emory Asthma Center and Pediatric Environmental Health Specialty UnitEmory University School of Medicine

Interaction of Environmental and GeneticFactors in the Natural History of AsthmaGenetic Factors:

AtopyAirways HyperreactivityEnvironmental Exposures: Allergens, Infections, Tobacco Smoke Triggers

Impact of Environmental Factors on T Lymphocyte DifferentionDefault PathwayUndifferentiated THelper CellIL-12Th2 PhenotypeB CellActivationEosinophilSignalingIL- 5IL- 4Th1 PhenotypeEnvironmentalExposures

Environmental Exposures Associatedwith 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 Associatedwith 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 weightadult 150 ml/min/kg/body weight

Trans-placental

- Exchange of fetal lung fluid with amniotic fluid

Breathing ZonesAdultInfantExposure to dustmite, cock roach,mercury

Specific Environments Prenatal

Home

School and day care

Food and water

Occupational

Medical treatments and cosmetics

Evidence that Prenatal Tobacco SmokeExposure 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 TobaccoSmoke Exposure on Lung Function in Boys with AsthmaLi et al, Am J Respir Crit Care Med 2000; 162: 2097% Changefrom UnexposedReference Group

Effects of Chronic Alcohol Abuse on LungAntioxidant CapacityBALGlutathione(umol)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 bio- allergens, VOCs, combustion sources

Modern homes and buildings better insulated - less air exchange

Asbestos and RadonAsbestos

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 AgentsPrecipitating AsthmaAgentMajor Sources

Allergens

Dust miteCarpet, mattresses, pillows

Animal Cats, dogs, rodents

Cock roachKitchens, bathrooms

MoldsBasements, bathrooms

Tobacco smokeCigarettes, pipes, cigars

Nitrogen oxides (NO2)Indoor combustion

VOCsFormaldehyde- pressed wood

OdorsSprays, 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 MiteDust miteHumid Environment

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 AgentsPrecipitating AsthmaAgentMajor Source

Ozone (O3)Hydrocarbon combustion

Sulfur DioxideFossil fuels, industry

ParticlesDiesel exhaust, wood

Acid aerosolsSouthwestern U.S.Mold sporesAlternaria, Aspergillus

Principal Components of SmogPollutantAir LimitAveraging Time

Ozone0.08 ppm8 hours

PM1050 g/m3Annual mean150 g/m324 hours

PM2.515 g/m3Annual mean65 g/m324 hours

SO20.03 ppmAnnual mean0.14 ppm24 hours

NO20.053 ppmAnnual mean

The London Air Pollution Crisis - 1952

Importance of Fine Particulate Air Pollution andMortality in 20 U.S. Cities 1987-1994 Pollutants surveyed:- fine particles < 10 m 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 g per cubic meter.Samet et al. N Engl J Med 2000; 343:1742

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 forChildren 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 andalbuterol before entering the trailer completely restoredlung 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 relationto 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 heat- ventilating air conditioning units (HVAC) and fan coil units (FCU). Vincent et al, Envir Res 1997; 75:100.

Typical Modern HVAC System

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. The School EnvironmentTurner-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.9 y/o with interstitial pattern and avianhypersensitivity pneumonitis

Respiratory Diseases Associated withInhalation of Inorganic Dusts (Pneumoconiosis)The accumulation of dust in the lungs and thetissue reaction to its presence.27 y/o sandblaster with apical nodularopacities and enlarged hilar lymph nodes

Medical TreatmentsIonizing 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