The Role of Environmental Exposures and Atopy in Asthma of the Elderly

Monroe James King, DOAssociate Clinical Professor of Medicine

College of Medicine, University of South Florida

Potential Conflict of Interest

Consultant to Pure Air Controls, US Energy Corporation, Clearwater, FL,

prior to 2007

What We Know About the Environment and Allergens in Asthmatics ?

In The General PopulationIndoor Air – allergens and pollutantsOutdoor Air – allergens and pollutants

In Older Adults No comprehensive reviews or meta-analysis*

Small studies

*PubMed and Web of Science search July 24, 2008; search terms included asthma and elderly, age over 40, reviews, meta -analysis.

Evidence in General Population

Clearing the Air: Asthma and Indoor Air Exposure1

Institute of MedicineFor EPA

2000National Academy Press

www.nap.edu

Indoor Air QualityPollutants 1

Biological

Animals: cats, dogs, rodents, birds

CockroachesHouse dust mitesEndotoxinsFungi or moldsHouseplantsPollenViruses and bacteria

Chemical

NOx

PesticidesOzoneEnvironmental tobacco smokeOther particulate matterSOx

Volatile organicsFormaldehydeFragrances

Evidence Levels1

A: Sufficient evidence of a causal relationshipB: Sufficient evidence of an associationC: Limited or suggestive evidence of an associationD: Inadequate or insufficient evidence to determine if an association existsE: Limited or suggestive evidence of no association

Clearing the Air 1 Development Exacerbations

House Dust Mites A A

Environmental Tobacco Smoke

PreschoolOthers

BD

PreschoolOthers

AC

Cats D A

Cockroaches PreschoolOther

CD

AC

Dogs D B

Fungi D B

Clearing the Air 1 Development Exacerbations

Formaldehyde D B

Pollen (Indoor) D D

VolatileOrganic Compounds D D

Rhinovirus E B

Endotoxins D D

Fragrances D C

“Damp Indoor Spaces and Health”Institute of Medicine for CDC 2003 2

Development Exacerbation (Symptoms)

Asthma C B

Upper Respiratory Symptoms

B

Cough B

Wheeze B

Dyspnea C

Meta-analysis reported 30-50% increase in respiratory and asthma related health outcomes .Fisk WJ et al in Indoor Air, 2007;Vol 17, (4) 284-296

Evidence Specific to Older Adults With Asthma

No meta-analysis or evidence based large studies

Several small studies of skin test and specific IgE prevalence studies

No allergen bronchial challenge studiesFew epidemiological studies of ER or hospital

admissions

Allergy Skin Tests in Older Subjects

N Age Skin Test Positive Percent to at least 1 of 8

NHANES II 3

U.S. Population/1986Study conducted 1980-81

2509 65-74 8

NHANES II 4

US Population/2000Retrospective study of same NHANES II population

3910 60-74 12.6

Studies of Skin Test or Specific IgE in Older Adults with Asthma

Location Ref / Date N MeanAge

Mean Age of Onset

Skin TestPositive %

Serum Spec IgE Positive %

Britain5/1972 15 >60 >60 27 ND

Tuscon6/1991 46 73 52 37 ?

Baltimore7/2001 75 74 ? 75 ND

New York8/2002 45 69 39 ND 60 (Cockroach 47%)

Clearwater,FL9

/2004 32 >64 ? ND 56

(Dust Mite - Der P)

Early and Late Onset Asthma

Location Ref/Date N MeanAge

Mean Age of Onset

Skin Test Positive %

Serum Spec. IgE

Positive %

Providence RI10

/199125 > 70 < 43 (N=13)

> 70 (N=12)620

ND

Rochester MN11

/199763 > 65 < 40 (N?)

> 41 (N?)> 65 (N?)

562120

NDNDND

Boston MA12

/199746 61 49 ± 15.7 ND 24 (cat)

25 (Der P 1)

Boston MA12

/1997 33 61 61 ND 18 (cat)

21 (Der P 1)

Allergy Data from TENOR Study13

CharacteristicsCharacteristics Younger – Younger – Age 18 - 64 Age 18 - 64

N = 2912N = 2912

Older – Age Older – Age

≥ ≥ 6565

N=566N=566

PP value value

Geometric Geometric Mean IgE, Mean IgE, IU/mlIU/ml

9090 6060 <.001<.001

Allergic Allergic Rhinitis

2134 (74 2134 (74 %)%)

341 (61 %)341 (61 %) <.001<.001

Atopic Atopic DermatitisDermatitis

424 (15%)424 (15%) 49 (9%)49 (9%) <.001<.001

Never Skin Never Skin TestedTested

202 (11%)202 (11%) 61 (16%)61 (16%) <.001<.001

Negative Skin Negative Skin teststests

100 (5%)100 (5%) 40 (10%)40 (10%)

Positive Skin Positive Skin TestsTests

1568 (84%)1568 (84%) 290 (74%)290 (74%)

Do Skin Tests Reflect Current Allergen Exposure ? 7

Allergen Levels Skin Test +/n (%)

Der P. Group 1 > 20 µg 11/42 (26)

< 20 µg 13/37 (35)

Cockroach 0.4 -17.2 U 4/19 (21)

Undetectable 17/56 (30)

Do Skin Tests Reflect Current Allergen Exposure to Pets? 7

Allergen Pet in home Skin test + % Positive

Cat 15 yes 5 33

60 no 19 32

Dog 20 yes 6 30

55 no 15 27

Do Positive Skin Tests And/Or Specific IgE Predict Clinical Allergy In Older Adults?

Natural Challenge or Exposure Room - No studies in older adults

Bronchial Challenge - Only small studies in general population. No studies found in older adults

Nasal Challenge14 - Few studies; older subjects less likely to have positive nasal challenge with positive skin test or specific IgE

Nasal Challenge to Allergens in Older Adults

LocationRef/Date/ Allergen

N Age Skin Test and/or Specific IgE Response

Nasal ChallengeResponse

Tampa FL 14

/2008/ Der P.28 ≥ 60

(Mean 68)11 Pos17 Neg

2 Pos2 Pos

20 20-59 (Mean 34)

10 Pos10 Neg

10 Pos10 Neg

Summary of IgE Evidence Specific to Older Asthmatics

Skin tests or serum specific IgE were positive in 0 to 75%.

Late onset asthmatics were less likely to have skin or serum specific IgE positive tests.

Positive skin tests did not reflect current exposure to allergens.

Neither skin test or serum specific IgE predicted nasal challenge response in older adults.

Outdoor Air Pollution

AssociationsSurvey of Los Angeles and San Diego traffic density

and outdoor air pollution levels. Traffic density and ozone levels associated with poor asthma control in elderly adults.15

Particulate air pollution and hospital admissions for cardiorespiratory diseases: are the elderly at greater risk? 16

What Questions Need Answering?

What research is needed?

Questions Specific to Asthma in Older Adults

Does evidence of allergy/environmental exposure in the general population apply to older adults?

Is airway response to the environment in older adults different to:

Allergens and other Pollutants?Temperature?

Questions Specific to Asthma in Older Adults

Does asthma of late onset (over age 40) have a different etiology and mechanism than childhood/young adult onset?

What is the role of non-IgE–mediated pathways in the development of asthma, and does this role suggest other biomarkers of effect that should be considered?

Questions About Methods Specific to Older Adults

Is it safe to do allergen challenges?Bronchial Nasal Segmental Allergen Rooms Bronchial-alveolar lavage Natural Exposure

Biopsy

Is it safe to do nonspecific (methacholine, histamine, or cold air) bronchial challenge after exposure to allergen?

Technical Capabilities and Limitations

Allergen tests and assays depend on well characterized allergens.

Skin tests in older subjects are sometimes limited by subjects’ skin aging or sun damage

Need age specific cut off levels for clinical significance of specific IgE serum and skin tests

Do antibodies present in skin or serum reflect antibodies in the bronchial mucosa and lungs? (Bronchial Associated Lymph Tissue)

Future Studies

Small Mechanistic Large Natural History Observational

New Methods to Determine Causation

Modifiers of Environmental Influence on Asthma In Elderly

Female GenderFemale Gender

ObesityObesity

Aspirin NSAIDSAspirin NSAIDS

New IdeasNew Ideas

GeneticsInfections or

InsultPollutants

GeneticsInfections or

InsultPollutants

Co-MorbidityCo-Morbidity

Dwelling TypeDwelling Type

Asthma Prevalence (2001-2003)

Asthma Prevalence By Age Group

0

2

4

6

8

10

12

0 - 4 5- 14 15 - 34 35 - 64 65 +

Age Range (Yrs.)

% P

op

ula

tio

n

Male

Female

From 2007 CDC Surv. Summ on Asthma

Gender Patterns for Adult Asthma:471,000 Hospitalizations in NY State

female versus male age specific admission rates

0

50

100

150

200

250

300

350

400

20 25 30 35 40 45 50 55 60 65 70 75 80

5 yr age intervals

ad

mis

sio

n r

ate

s p

er

10

0,0

00

male 1990 female 1990

male 1995 female 1995

male 2000 female 2000

male 2005 female 2005

Lee GB. J Allergy Clin Immunol 2008;121 (2): S1

References1. Institute of Medicine. Committee on the Assessment of Asthma and Indoor Air. Division of Health Promotion and Disease Prevention. Clearing the Air: Asthma and Indoor Air Exposures. Washington, DC: National Academy Press; National Academy of Sciences; 2000. Available at: http://www.epa.gov/asthma/publications.html#Clearing_the_Air. Accessed July 24, 2008.

2. Institute of Medicine. Committee on Damp Indoor Spaces and Health. Board on Health Promotion and Disease Prevention. Damp Indoor Spaces and Health. Washington, DC: National Academy Press: National Academy of Sciences; 2004. ISBN 0-309-09193-4. Available at: www.nap.edu/catalog/1011.html. Accessed July 24, 2008.

3. Gergen PJ, Turkeltaub PC. Percutaneous Immediate Hypersensitivity to Eight Allergens. United States, 1976-80. Washington, DC: National Center for Health Statistics. Vital and Health Statistics. July 1986. DHHS Pub No.(PHS) 86-1685. Series 11, No. 235.

4. Gergen JP, Turkeltaub PC, Sempos CT. Is allergen skin test reactivity a predictor of mortality? Findings from a national cohort. Clin Exp Allergy. 2000;30(12):1717-1723.

5. Lee HY, Stretton TB. Asthma in the elderly. Br Med J. October 14, 1972; 4:93-95.

References (continued)

6. Burrows, B, Barbee RA, Cline MG, Knudson RJ, Lebowitz. Characteristics of asthma among elderly adults in a sample of the general population. Chest. 1991;100(4):935-942.7. Huss K, Naumann PL, Mason PJ, et al. Asthma severity, atopic status, allergen exposure, and quality of life in elderly persons. Ann Allergy Asthma Immunol. 2001;86:524-530.8. Rogers L, Cassino C, Berger KL, et al. Asthma in the elderly: cockroach sensitivity and severity of airway obstruction in elderly nonsmokers. Chest. 2002;122(5):1580-1586.9. King MJ, Bukantz SC, Phillips S, Mohapatra SS, Tamulis T, Lockey RF.

Serum total IgE and specific IgE to Dermatophagoides pteronyssinus, but not eosinophil cationic protein, are more likely to be elevated in elderly asthmatic patients. Allergy Asthma Proc. 2004;25(5):321-325.10. Braman SS, Kaemmerlen JT, Davis SM. Asthma in the elderly. A comparison between patients with recently acquired and long-standing disease. Am Rev Respir Dis. 1991;143(2):336-340.11. Reed CE. The role of allergy and airway inflammation. In: Barbee RA,

Bloom JW, eds. Asthma in the Elderly. New York, NY: Marcel Decker; 1997:33-52.

References (continued)12. Litonjua AA, Sparrow D, Weiss ST, O’Connor GT, Long AA, Ohman JL Jr.

Sensitization to cat allergen is associated with asthma in older men and predicts new-onset airway hyperresponsiveness. The Normative Aging Study. Am J Respir Crit Care Med. 1997;156(1):23-27.

13. Slavin RG, Haselkorn T, Lee JH, Zheng B, Deniz Y, Wenzel SE, and the TENOR Study Group. Asthma in older adults: observations from the epidemiology and natural history of asthma: outcomes and treatment regimens (TENOR) study. Ann Allergy Asthma Immunol. 2006;

96(3):406-414.

14. King MJ, Tamulus T, Lockey RF. Prick puncture skin tests and serum specific IgE as predictors of nasal challenge response to dermatophagoides pteronyssinus in older adults. Ann Allergy Asthma Immunol. 2008;101(1):12-17.

15. Meng YY, Wilhelm M, Rull RP, English P, Ritz B. Traffic and outdoor air pollution levels near residences and poorly controlled asthma in adults. Ann Allergy Asthma Immunol. 2007;98(5):455-463.

16. Anderson HR, Atkinson RW, Bremner SA, Marston L. Eur Respir J Suppl. May 2003;40:39s-46s.

Questions About Methods Specific to Older Adults

How do we define asthma for studies?SeverityDuration/ age of onsetDiagnosis by questionnaire or objective measures – Is spirometry, reversibility, provocation necessary?

Do we need new age specific cut off levels and norms for spirometry or other pulmonary function tests?