Asthma in Children: Risk Factors

Dennis R. Ownby, MDChief, Division of Allergy,Immunology & RheumatologyGeorgia Health Sciences UniversityAugusta, GA, USA

Environmental Exposures

Disclosures

In the past year I have been: A consultant to CarboNix, LLC Advisory board, Merck Childhood

Asthma Network No discussion of off label drug use Research Support: National

Institutes of Health Legal Fees: None Gifts: None

Concepts to Explore

What exposures allow wheezing in infancy to become asthma in childhood

How should we define “exposures” How do exposures interact with genetic

predisposition Are environmental exposures important

only in infancy or throughout life Have we been, “looking for love in all

the wrong places”

Accepted Knowledge

Most children with asthma are sensitized to allergens

Strong association between allergic sensitization and persistence of asthma

Stronger association between sensitization to perennial allergens and asthma than seasonal allergens

Early Allergen Sensitization and Chronic Asthma in Children

German MAS Study 1314 children: birth to 13 years of

age Allergen exposure at 6 & 18 months

and at 3, 4, 5 years Lung function at 7, 10 ,13 years IgE’s at 1, 2, 3, 5, 6, 7 and 10 years

Illi S, et al. Lancet 2006;368:763-770

Prevalence of Current Wheezing: Prevalence of Current Wheezing: Birth to 13 YearsBirth to 13 Years

Illi S, et al. Lancet 2006;368:763-770

at school ageNon-atopic, n=94Atopic, n=59

Previous Findings

Sporik et al, NEJM 1990 RR = 4.8 for asthma at age 11 associated with Der p 1>10 μg/g dust at 1-2 yrs

Burr et al, Arch Dis Child 1993 No association between dust mite levels at 1 yr and wheeze or atopy or +ST to mites at 7 yrs

Lau et al, Lancet 2000 No association between dust mite levels in infancy and asthma at 7 yrs

Johnson et al, J Allergy Clin Immunol 2004 No association between dust mite levels in infancy and seroatopy, atopy or asthma at 6-7 yrs

Dust Mite Exposure and Wheezing in MAS

= 1st quartile of dust mite at 6 months of age = 4th quartile of dust mite at 6 months of age

Lau S, et al. Paediatric Resp Rev 2002;3:265-272

Cigarette Smoke Exposure and Childhood Asthma

Both chemicals and particulates from cigarette smoke exacerbate asthma symptoms

Maternal smoking during pregnancy increases risk of asthma in most studies

Studies are inconsistent concerning the effects of smoke exposure during childhood and the risk of asthma

Prevalence of Allergic Sensitivity with Exposure to Parental Smoking

P = .07 P = .18 P = .28 P = .28

Perc

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t of

Child

ren

Ownby DR, et al. Unpublished

Cigarette Smoke Exposure and Allergic Sensitization in MAS

Lau S, et al. Paediatric Resp Rev 2002;3:265-272

Home VOC Exposure and Asthma in Young Children

Population based case-control study 88 cases (ED for asthma), 104 controls Asthma 25 months old, controls 20

months VOCs measured 1 week after ED visit

then 6 months later Active charcoal sampling in living room Ten VOCs sampled

Rumchev K, et al. Thorax 2004;59:746

Rumchev K, et al. Thorax 2004;59:746

Association of VOC Exposure and Asthma

VOC Exposure and Asthma

VOC’s given off by many products Indoor VOC’s 2-5 times outdoor levels NHANES 1999-2000 669 subjects Representative subgroup Wore 3M 3520 Organic Vapor

Monitors 10 VOC’s were measured Physician diagnosed asthma = 12.5%

Arif AA, Shah SM. Int Arch Occup Environ Health 2007;80:711-719

VOC Exposure and Asthma Risk

Arif AA, Shah SM. Int Arch Occup Environ Health 2007;80:711-719

Independent Variable

Odds Ratio** 95% CI

Factor 1* 1.63 1.17 – 2.27

Benzene 1.33 1.13 - 1.56

Toluene 1.34 1.01 – 1.78

o-Xylene 1.21 0.93 – 1.58

m,p-Xylene 1.33 1.08 – 1.64

*Factor 1 = aromatic compounds, **OR adjusted for age, race, sex, BMI, atopy,Smoking, ETS, poverty level, and interactions

Common Household Chemicals and Allergy Risks

Preschool children:198 cases, 202 health control

Measured 8 classes of VOC’s from bedroom air samples

Only propylene glycol and glycol ethers related to being a case

Choi H, et al. Plos One 2010;18(5):e13423

Common Household Chemicals and Allergy Risks

Choi H, et al. Plos One 2010;18(5):e13423

Fold

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Pets Contribute More than Allergens to Homes

18 house dust samples from WHEALS 6 ≥ 1 dogs, 6 ≥ 1 cat, 6 without pets PhyloChip analysis of microbial taxa

present Insufficient DNA in 2 dust samples

Homes with dogs More types of bacteria present, richer, p

< .04 More diverse, p < .04

19Fujimura KE, et al. J Allergy Clin Immunol 2010;126:410-412

Bacterial Communities in House Dust from Dog verses No-Pet Households

20Fujimura KE, et al. J Allergy Clin Immunol 2010;126:410-412

Pets Alter Home Dust Microbiome

337 bacterial taxa significantly increased in dog-owning homes• Proteobacteria (112 taxa)• Actinobacteria (63 taxa)• Firmicutes (47 taxa)• Bacteroidetes (41 taxa)• Spirochaetes (22 taxa)• Verrucomicrobia (7 taxa)

• These are phyla common in the human gastrointestinal tract

21Fujimura KE, et al. J Allergy Clin Immunol 2010;126:410-412

Movement of Bacteria from House Dust to Infant Gut

Hand-to-mouth activity Well studied by toxicologists Studies demonstrate that hand-to-

mouth activity relates dust and infant concentrations of toxins

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Soil and House Dust Ingestion by Children

Soil and dust ingestion directly related to hand to mouth and object to mouth activity in children

Hand to mouth activity is highly variable in children and varies indoors and outdoors

Average dust ingestion is 30–100 mg/day for children 6 months – 11 years of age

Pica (ingestion of large quantities of soil ~5 gm/day) is relatively common in children

U.S. EPA. Child Specific Exposure Factors Handbook 2008

Role of Unpasteurized Milk

Multi-center European study (PARSIFAL) 14,893 children 5-13 years-of-age Farm milk inversely associated with asthma,

adjOR = 0.74 (95% CI 0.61-0.88) Rhinoconjunctivitis, sensitization to pollen

and food mixes also significantly inversely associated with farm milk

Waser M, et al. Clinical Exp Allergy 2006;37:661-670

Drinking Water Microbes and Atopy

563 children, 7-16 years, living in Finnish- and Russian-Karelia

Skin prick tested with 14 common allergens and foods

Finnish children significantly more sensitization – 48% vs 16%

Multivariable analysis – sex, cat < 1 yr, density of microbes in water

Von Hertzen L, et al. Allergy 2007;62:288-292

Does Pet Ownership Impact House Dust and Stool Microbiota?

26Lynch S, et al. unpublished

Feeding Bacteria or Bacterial Products Affects Response to Viral Respiratory Infection in Humans

Oral treatment with a mixture of lyophilized bacterial extracts (OM-85BV) for first 10 days of 3 consecutive months reduced cumulative number of RTI’s and of wheezing episodes per child/year and reduced duration of wheezing episodes (p <0.001)

Razi, J Allergy Clin Immunol 2010; 126:763-0

Twice daily treatment with L. acidophilus and B. animalis for six months reduced fever, rhinorrhea, cough, antibiotic use, and missed school days in 3-5 y.o. children.

Leyer G, Pediatrics, 2009; 124:172-179

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Conclusions

Exposure to cigarette smoke increase asthma symptoms but not asthma or allergic sensitization

Exposures to volatile organic compounds appears to increase asthma in children

Microbes ingested by children in infancy have strong effects on the risk of developing allergic sensitivity and disease and response to viral respiratory infections