the role of environmental exposures and atopy in asthma of the elderly monroe james king, do...
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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?
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