Environmental Causes of Asthma in Children A Debate

Environmental Causes of Asthma in Children A Debate of Causes vs. Triggers Emily Cohn, Jahan Mohiuddin

What is Asthma? • Chronic disease that inflames and narrows the airways • Symptoms include: wheezing, chest tightness, shortness of breath, and coughing • Inflammation makes airways hypersensitive and reactive • When airways react, the muscles constrict, narrowing the airway • Increased mucous production

Pathophysiology of Asthma • A chronic condition in which the airways periodically constrict, inflame, and secrete excessive amounts of mucus. • 2 types: allergic and non-allergic. • Most common chronic childhood disorder in developed countries.

Allergic Asthma • Triggered by inhaling allergens such as dust mites, pet dander, pollens, mold, etc. • Ig. E antibodies produced by B cells activate mast cells • Mast cells initiate inflammatory response with release of histamine and other granules. • One of the effects of histamine is an increase in blood vessel permeability, leading to edema (swelling).

Non-Allergic Asthma • Very similar symptoms as allergic asthma but non-allergic asthma is characterized by the absence of an immune response. • Caused by factors such as anxiety, stress, exercise, cold air, dry air, hyperventilation, smoke viruses or other irritants

Why Is Asthma Important? • According to Fisk (2000), “asthma, allergic rhinitis, and other associated airway allergic diseases cost $23 billion in terms of health care and indirect costs including lost work and lost school days. ” • Landrigan et al. (2002) estimated the total annual costs from US children’s asthma caused by environmental exposures at $2. 3 billion. • Between 1980 and 1994 the prevalence of asthma in the US increased 75%.

Asthma Prevalence United States, 1980 -2004 Lifetime Current 12 -Month Attack Source: National Health Interview Survey; National Center for Health Statistics

Asthma Prevalence by Sex United States, 1980 -2004 • Female § Male 12 -Month Lifetime Current Attack Source: National Health Interview Survey; National Center for Health Statistics

Child and Adult Asthma Prevalence United States, 1980 -2004 • Child § Adult Lifetime Current 12 -Month Attack Source: National Health Interview Survey; National Center for Health Statistics

Adult and Child Asthma Prevalence United States, 1997 -2004 Child Lifetime Adult Lifetime Child Current Adult Current Child Attack Adult Attack Source: National Health Interview Survey; National Center for Health Statistics

12 -Month Asthma Prevalence by Race: United States, 1980 -1996 Black White Source: National Health Interview Survey; National Center for Health Statistics

Asthma Prevalence by Race/Ethnicity United States, 1997 -2004 Lifetime ▲ Black NH Current § White NH w Hispanic Attack Source: National Health Interview Survey; National Center for Health Statistics

Current Asthma Prevalence by MSA Size: United States, 2001 MSA size Source: National Health Interview Survey; National Center for Health Statistics

Current Asthma Prevalence by Poverty Status: United States, 2004 Poverty Source: National Health Interview Survey; National Center for Health Statistics

Why is asthma incidence higher now? • Hygiene Hypothesis – Emphasis on hygiene and sanitation has changed living conditions and reduced infections – Different environmental exposure – Increased risk for atopy and asthma

Causes and Triggers Causes • Genetic • At least 25 genes associated with asthma 1 • Environmental Factors • Only indoor agents are involved. • Environmental tobacco smoke 2 • Poor air quality 2 • Mold • Dust mites • Gene-environment interactions Triggers • Allergens • Airborne irritants • Respiratory infections • Exercise • Weather • Strong emotions • Some medications • Ex: aspirin

Environmental Agents: Causes or Just Triggers? Can environmental factors cause the development of asthma? Or do environmental factors only trigger asthmatic attacks?

What the literature has to say • Jaakkola et al. (2005) found that children living in homes with mold odor had a >100% increased risk of developing asthma in the following 6 years. • Strachan (1988), Dales et al. (1991), Brunekreef (1992), and other studies had supporting findings. • According to Etzel (2003) and Strachan (2000), environmental tobacco smoke and indoor dust mites strongly increase the likelihood of asthma development.

Gold (2000)

Indoor Exposure Asthma Development Asthma Exacerbations House dust mite Increased Environmental Tobacco Smoke Probably increased Increased Cockroach Maybe Increased Cat Maybe Increased Dog Maybe Increased Probably Increased Etzel RA (2003)

House Dust Mites • “The Institute of Medicine has concluded that sensitization to house dust mites is an important risk factor for asthma development” Etzel (2003) • “These data strongly suggest that dust mite exposure is a risk factor for the development of symptomatic asthma in children” Gold (2000)

Environmental Tobacco Smoke • Prenatal maternal smoking is correlated with reduced infant airway size, among many other things. Gold (2000) • The influence of ETS on the development of asthma among children less than 6 years old is much greater than that among school-age children. Gold (2000)

Non-Environmental Causes • Viral or sinus infections and antibiotic use - early antibiotic use that prevents differentiation toward TH 1 (Delfino 2002) -RSV infection in infants is asthma risk factor (Sigurs 2000) • Diet • Obesity • Genetics

Diet and Asthma • “Westernization” of societies caused change in diet • Between 1961 -1985, the British diet decreased: – Fresh fruit consumption by 26% – Green vegetables by 51% • reduced antioxidants causes increased susceptibility to oxidant attack and airway inflammation Seaton 1993

Obesity and Asthma • Reduced residual capacity, increased airway responsiveness • In children, might affect lung growth leading to reduced pulmonary function • Increased airway contractility through chronic, lowgrade inflammation • Alteration of serum concentrations of hormones which could affect airway function Shore 2005

Genetic Factors of Asthma • No simple Mendelian pattern of inheritance • Exhibits polygenic inheritance and genetic heterogeneity • six loci have been implicated: -chromosomes 6 p 21, 5 q, 11 q 13, 13 q, and 12 q Sandford 2000

Evidence of Genetic Basis in Causation of Asthma • “in families with asthma in successive generations, genetic factors alone explained as much as 87% of the development of asthma in offspring (Holloway, 1999) ” • Harris et al. twin study -RR for identical twins was 17. 9 -RR for fraternal twins was 2. 3

Factors which suggest genetic components in causation of asthma • Prevalence of asthma in the US differs between: - males and females -racial groups

Outdoor air pollution and asthma • Lang and Polansky study in Philadelphia between 1969 -1991: - concentrations of all major air pollutants declined -asthma morality rates increased • American six cities study found no association between exposure to PM, NO 2, SO 2 and prevalence of asthma • Leipzig and Munich study Seaton 1993

Non-environmental Triggers • • Gastroesophageal reflux (AAAAI) Exercise Smoking Stress

Discussion Questions • What do you think is the primary cause of asthma? • If there is an environmental component to asthma, what kinds of public health implications are there? • What types of public health measures need to be created/ enforced to reduce the burden of asthma and other chronic diseases? • Why does correlation not equal causation? • Why do people so often make the mistake of equating the two? • How does this fact make it difficult to prove that environmental factors can cause the development of asthma? • What are your thoughts on the hygiene hypothesis?

References Ober C, Hoffjan S (2006). "Asthma genetics 2006: the long and winding road to gene discovery". Genes Immun 7 (2): 95– 100. Gold DR, Wright R (2005). "Population disparities in asthma". Annu Rev Public Health 26: 89– 113. Fisk, WJ. 2000. Estimates of potential nationwide productivity and health benefits from better indoor environments: an update. In: Indoor Air Quality Handbook (Spengler J, Samet JM, Mc. Carthy JF, eds). New York: Mc. Graw Hill, 4. 1– 4. 36. Landrigan, PJ; Schecter, CB; Lipton, JM; Fahs, MC; Schwartz, J. Environmental pollutants and disease in American children: estimates of morbidity, mortality, and costs for lead poisoning, asthma, cancer and developmental disabilities. Environ Health Perspect. 2002; 110: 721– 728. Jaakkola, JJK; Hwang, BF; Jaakkola, N. Home dampness and molds, parental atopy, and asthma in childhood: a six-year population-based cohort study. Environ Health Perspect. 2005; 113: 357– 361. Etzel RA. How environmental exposures influence the development and exacerbation of asthma. Pediatrics. 2003. 112(1 Pt 2): 233 -9. Strachan DP. Damp housing and childhood asthma: validation of reporting of symptoms. BMJ 1988; 297: 1223 -6 Dales RE, Burnett R, Zwanenburg H. Adverse health effects among adults exposed to home dampness and molds. Am Rev Respir Dis 1991; 143: 505 -9 Brunekreef B. Associations between questionnaire reports of home dampness and childhood respiratory symptoms. Set Total Environ 1992; 127: 79 -89 Strachan DP. The role of environmental factors in asthma. Br Med Bull. 2000. 56(4): 865 -82. Gold DR. Environmental tobacco smoke, indoor allergens, and childhood asthma. Environ Health Perspect. 2000 Aug; 108 Suppl 4: 643 -51. Brim SSN. Asthma prevalence among US children in underrepresented minority populations: American Indian/Alaska native, chinese, filipino, and asian indian. Pediatrics (Evanston). 2008; 122(1): e 217 -22.

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