Environmental Influences on Asthma

Environmental Influences on Asthma Steven R. Grandgeorge, MD Dartmouth Hitchcock - Manchester

Indoor Air Allergens • Most commonly identified sources of indoor allergens are: • Dust mites • Cockroaches • Domestic pets • Feral animal pests • Fungi • Plants and pollens • Occupational

Mold Allergy Mold can cause diverse health effects, related to the type of exposure and the unique characteristics of the individual • Allergic and other immunologic respiratory disease • 3.6% of general population test + for one or more molds • 22-38% of asthmatics test + for one or more molds • Approx. 50% of mold allergic patients express clinical disease • Mycotoxicosis • Documented with ingestion of contaminated foods • Airborne toxin has been detected with heavy industrial mold contamination • Not a concern in residential settings • NO “Toxic Mold Syndrome” • Infection • Aero-irritation • Psychogenic

Mold Allergy: Home Dampness • Numerous studies of both adults and children in different countries have found a significant correlation between exposure to damp indoor environments (as evidenced by signs of mold growth) and the presence of various respiratory symptoms including cough, wheeze, rhinitis, and eye and nose irritation • Symptoms occur without regard to allergic status or to mold sensitization !

Mold Allergy: Home Dampness • Numerous studies of both adults and children in different countries have found a significant correlation between exposure to damp indoor environments (as evidenced by signs of mold growth) and the presence of various respiratory symptoms including cough, wheeze, rhinitis, and eye and nose irritation • Symptoms occur without regard to allergic status or to mold sensitization ! Aero-irritant effect

Mold Allergy: Tri-State Homes • Affordable prefabricated homes in Midwest US • 1960s-1970’s • Occupants noted: • Increased respiratory illnesses • Increased moisture • Mold growth in the homes • Premature decay of the structure

Mold Allergy: Tri-State Homes Wisconsin Department of Health and Social Services findings: • Compared environment and health of occupants of Tri-State Homes to that of a control group living in standard stick built homes • Tri-State residents had increased cough, phlegm, shortness of breath, nocturnal wheeze, stuffy nose, burning eyes and throat, and frequent colds • Homes had an impermeable, improperly placed vapor barrier

Mold Allergy: Tri-State Homes University of Wisconsin study findings: • High incidence of upper and lower respiratory irritation • Less than expected incidence of positive allergy tests to molds • Very high dust mite counts • Very high incidence of positive tests to dust mites

Mold Allergy: Summary • There is relatively little research • There is NO “toxic mold syndrome” • As an indoor allergen, mold is considered a minor participant • Most who think they are allergic to mold are likely bothered by aero-irritants or other allergens (mites) • Mold may be a marker for poor indoor air quality

Dust Mite Allergy: Biology • •Sources of house dust mite allergen • - Fecal matter and mite bodies are the major sources of allergen • Mites obtain and maintain water balance by absorbing water from the water vapor in air • Mite levels fluctuate relative to ambient humidity Indoor humidity Homes without A/C or dehumidifiers Ave. live mites/g dust (JACI 2001; 107: 99-104.)

Dust Mite Allergy: Distribution Major mite breeding sites in homes: Mite allergen in other locations: • Clothing: Small amts of live mites and allergens • Stuffed toys: Very low allergen levels • Offices: Usually low (occasional exception) • Schools: Usually low (occasional exception) • Churches: Low • Hotels: Significant amounts in beds • Hospitals: Low levels • Automobiles: Very low levels

Dust Mite Allergy: Distribution Mite allergen location in homes • Most mite allergen is associated with large dust particles that settle quickly (within 20-30 minutes) • Airborne allergen is low or non-existent in the absence of disturbance • Little allergen is found on vertical walls and tops of hard surface furniture • Little allergen on smooth surface floors if cleaned regularly

Pet Allergens: Biology Characteristics of pet allergens • Cat allergens • Secreted by sebaceous glands onto the skin and fur (also sublingual salivary glands and anal glands) and is under hormonal control • Secreted in copious amounts and accumulates in house dust • Dog allergens • Secreted by parotid gland and sebaceous glands • There is NO hypoallergenic dog; the breed of dog does not relate to the amount of allergen produced

Pet Allergens: Distribution Differencesfrom dust mite allergens • Distributed on small particles that remain airborne for long periods • Airborne levels increase 5x when pet is in the room • Sticky; high levels found on walls and other surfaces • Clothing is an important means of distributing pet allergen to pet-free environments

Pet Allergens: Distribution National Survey of Allergens in Homes • Dog and cat allergens are detected in 100% and 99.9% of homes respectively • For dog, 34.9% exceeded the asthma symptom threshold level (9.3% of homes w/o dogs exceeded the threshold level) • For cat, 34.7% exceeded the asthma symptom threshold level (15.7% of homes w/o cat exceeded the threshold level)

Pet Allergens: Distribution Impact of school exposure • Pet allergen levels in schools are high enough to sensitize and to induce asthma symptoms • Increased symptoms, medication requirements, and risk of exacerbations has been correlated with high numbers of cat-owner classmates • Cat allergen levels in the homes of non-cat owner students correlate with cat allergen levels in schools

Allergen Avoidance Strategies Relocation Reservoir removal Allergen avoidance Air filtration Source removal

Allergen Avoidance: Removal of biological sources Effect of Pet Removal on Pet Allergic Asthma • n=20 (10 removal; 10 keeping) • Follow-up ≥ 1 year • In the removal group: • Significantly greater improvement in BHR • Significantly lower ICS dosage (Shirai et al. Chest 2005;127: 1565-71)

Allergen Avoidance:Multi-targeted approach Results of a home-based environmental intervention among urban children with asthma (NEJM 2004; 351: 1068-80) • Interventions • Education • Impermeable mattress/pillow covers • HEPA-filtered vacuum • HEPA air filter • Professional cockroach extermination

Allergen Avoidance:Multi-targeted approach Results of a home-based environmental intervention among urban children with asthma (NEJM 2004; 351: 1068-80) • Results: • Decreased asthma symptoms • Reduction in disruption of caretaker activities • Decreased sleep loss • Decreased missed school • Decreased ED visits $1500 to 2000 / child / 2 years

Indoor Air Allergens: Assessing Relevance Allergic symptoms + Positive test + Exposure “Relevant allergen” =

Are All Allergens Created Equal? • Response to allergens • may differ by: • Frequency of sensitization • Magnitude of IgE response • Exposure/sensitization relationship • Development of tolerance Sensitization Dust mite Exposure Cat Sensitization Exposure

Dermatophytes Cockroaches* Ladybugs Helminths Monkeys Scabies Reptiles Grasses* Humans Rodents* Fungi* Trees* Dogs* Mites* Birds Cats* Dinosaurs Great Cretaceous Catastrophe X 80 Million Mammals 300 Million • * Major inhalant allergen • * Allergens inducing tolerance 600 Million ║ 1200 Million 1500 Million The relevance of evolutionary distance to immunogenicity and cross-reactivity.

Avoidance of Indoor Allergens: Summary • Identifying the important allergen(s) may be the key to success • Testing is required to reliably determine sensitivity to perennial indoor allergens • Studies of allergen avoidance measures have largely been disappointing • Individual avoidance measures are generally ineffective • Effective allergen avoidance requires a multifaceted, comprehensive approach

Air pollution: The Beijing Olympics

Air quality issues may be of particular concern for New Englanders New England lies directly downwind of major urban and industrial centers in the United States. The climate gradient across New England is one of the steepest in the country. Even though the region is small geographically, the region is influenced by both polar and tropical air masses.

London: Mid-day in December 1952

London Killer Fog, December, 1952 UK Met Office, 2009

Common pollutants that are of human respiratory health concern Sulfur dioxide (SO2) Nitric oxides (NOx) Ozone (O3) Carbon dioxide (CO2) Particulate matter (PM)

Air pollutants could impact atopic disease at various levels Allergen Sensitization Allergic inflammation, Bronchial hyperreactivity Symptoms (wheeze, cough, sneeze, etc.) Pollutant “Adjuvant” or “cause” “Exacerbating factor” Pollutant “Trigger” Pollutant

Asthma exacerbations increase as ozone pollution exposures increase AJRCCM 1997; 155: 654-60.

Age-related association of PM and ozone with asthma hospitalizations Estimated relative risks of asthma hospitalization per IQR (interquartile range) increase in the average PM (12 µg/m3 ) and ozone (22 ppb) by age. JACI 2010; 125: 367-73

Age-related association of PM and ozone with asthma hospitalizations Estimated relative risks of asthma hospitalization with increasing PM or ozone exposure. JACI 2010; 125: 367-73

Effects of air pollution on asthma In patients with asthma, studies have shown that exposure to various pollutants has been associated with all of the following: • Increased ER visits and hospitalizations • Increased symptoms and medication use • Decreased pulmonary function • Increased bronchial hyper-responsiveness • Increased airway inflammation

DEP augments allergen-specific IgE in humans Further… Air pollution can interact with pollen grains, leading to an increased release of antigens thereby increasing allergenicity. Air pollution can interact with paucimicronic allergen-carrying plant particles allowing them to be more easily inhaled to the peripheral airways. IgE ( U/ml) Effect of ragweed or ragweed plus DEP challenges on ragweed specific IgE in nasal washes. (J Immunol. 1997; 158: 2406-13.)

Air pollution (ozone) &/or exercise as a cause of asthma? Effect of number of team sports played on the risk of new asthma diagnosis in high and low ozone communities. N = number of cases of asthma. RR = relative risk. Lancet 2002; 359: 386-91.

Interaction of atopy and chlorinated pool exposure on rhinitis and asthma risk Percent with hay fever Percent with asthma CPA (hours) CPA (hours) Prevalence of children with allergic rhinitis or asthma according to the CPA (chlorinated pool attendance) with atopic status. Bernard et al. Pediatrics 2009; 124: 1110-8. Bernard et al. Environ Health Perspect 2006; 114: 1567-73.

Air pollution as a cause of asthma? Increased risk of asthma in children living near roadways with high traffic volume. In primary school children the relative risk increased 1.8 per 30 meter increment. (AJRCCM 2009; 164: 2177-80.) Increased asthma in children living near petrochemical plants. (JACI 2009;123: 632-8.)

Health benefits of O3 reduction Reduction in vehicle exhaust and O3 production during the 1996 Summer Olympic games in Atlanta, GA, resulted in a reduction of acute asthma care in children aged 1-16 years. Percent decrease Friedman et al. JAMA 2001; 285: 897-905.

Pollutant levels during the 1996 Summer Olympic Games, Atlanta, GA Peak daily zone levels decreased 27.9%, from 81.3 ppb pre-Olympics to 58.6 ppb during the Olympic games. Peak weekday morning traffic counts dropped 22.5%. Friedman et al. JAMA 2001; 285: 897-905.

Atmospheric CO2 concentration and temperature change Projected concentrations of CO2 during the 21st century are 2-4 times pre-industrial levels

Atmospheric CO2 concentration and temperature change, 1860-2007 Changes in annual global mean surface temperatures and carbon dioxide concentrations since 1860 relative to 1961-1990 average values.

Health Impacts of Climate Change Temperature-related illness and death Extreme weather-related health effects Air pollution-related health effects Allergic disease Water and food-borne disease Vector-borne and rodent-borne diseases Effects of food and water shortages Mental, nutritional, infectious, and other health effects Environmental refugees Heat stress, cardiovascular failure Injuries, fatalities Asthma, cardiovascular disease Respiratory allergies, asthma Malaria, dengue, others Cholera, crypotosporidosis, others Malnutrition, diarrhea Anxiety, PTSD, stress, depression Forced migration, civil conflict Climate change Temperature Heat waves Extreme weather Precipitation Sea level rise

Effect of extreme temperatures when mean temperature increases IPCC 2007

European heat wave, 2003 Confirmed excess mortality Time line (France) Mortality in 13 French cities during the August 2003 heat wave. Am J Public Health 2004; 94: 1518-20. European mortality during the August 2003 heat wave. Public Health 2006; 120: 585-96.

Climate change and severe weather events, 1972-2004 Intensity of hurricanes (categories 1-5) 1970-2004, including number of storms by category (A) and proportion of storms in each category (B). Science 2005;309: 1844-6.

How much warming can we expect? 2020-2029 2090-2099 Global warming 2.8ºC IPCC 2007

Environmental Influences on Asthma