Transcript Irritant-induced Asthma

Non-RADS Irritant Asthma
Paul K. Henneberger, MPH, ScD
Division of Respiratory Disease Studies
National Institute For Occupational Safety & Health
Centers for Disease Control and Prevention
3rd Jack Pepys Workshop
Saturday, May 19, 2007
Montreal, Quebec
The findings and conclusions in this presentation have not been formally
disseminated by the National Institute for Occupational Safety and Health and
should not be construed to represent any agency determination or policy.
Outline
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Selected questions from 2nd Pepys
Workshop statement
Background: findings before last Workshop
Examples of findings since last Workshop
Can we answer selected questions from the
2nd Workshop?
Questions for discussion today
Selected questions and goals from
the 2nd Pepys Workshop:
Irritant-induced Asthma
43. Are underlying host factors more important
in the response to low-level irritant
exposures than to massive accidental
exposures?
33. Biological markers to identify the effects of
irritants on the expression of asthma are
needed
Background: Irritants, atopy, and
asthma
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Preller 1996 study of pig farmers
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Atopy associated with non-allergenic
quaternary ammonium compounds (QACs)
Symptoms consistent with asthma were
associated with atopy + exposure to QACs
Brooks 1998: Pre-existing allergic/atopic
status and/or pre-existing asthma were
significant contributors to not-so-sudden,
irritant-induced asthma
Background: Biomarkers studied by
Bernard & colleagues
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Isolated pneumoproteins in serum
and used as indicators of lung
epithelium damage and permeability
SP-A and SP-B: Alveolar surfactant
associated proteins A and B
CC-16:
– Antioxidant 16 kDa cell protein
– Small anti-inflammatory protein secreted
by non-ciliated bronchiolar Clara cells
Study by Bernard & colleagues:
Carbonnelle 2002
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Studied children and adults who attended
indoor chlorinated pool
Exposure to chlorine by-products
including nitrogen trichloride (NCl3)
Findings:
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Increases in SP-A and SP-B associated with
cumulated pool attendance
Little change in CC-16 levels
Conclude: Exposure impacted deep lung
Examples of findings since
the 2nd Jack Pepys Workshop
1. Asthma associated with low-level
irritants
2. Asthma associated with low-level
irritants only in atopic subjects
3. Low-level irritants acting in
combination with other agents
4. Biomarkers of irritant exposure
Asthma-irritant association
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Medina-Ramon 2005: asthma
associated with bleach use in cleaners
Nickmilder & Bernard 2007
– From the International Study of Asthma
and Allergies in Childhood (ISAAC)
– Subjects: children 13-14 yrs old
– For each additional chlorinated pool per
105 inhabitants, increase of 2.7% (95% CI
1.9%-3.5%) for ever-asthma
Asthma-irritant association:
European Community Respiratory
Health Survey (ECRHS) farmers
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Smit 2007 used ECRHS data
Hay fever (OR=2.1, 95% CI 1.0-4.4) but not
asthma (OR=1.7, 95% CI 0.7-3.9) associated
with use of QACs
Asthma-irritant association only
in atopic subjects: Indoor pools
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Bernard 2006 study of pool attendance
on among 341 children 10-13 yrs old
Asthma associated with cumulated
pool attendance (CPA) only if child also
atopic (total IgE>100 kIU/L)
OR=1.8 (95% CI 1.1-2.7) for each 100
hour increase in CPA for atopics
QACs as adjuvants without
respiratory exposure
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Larsen 2004 exposed mice by
subcutaneous injections to ovalbumin
and quaternary ammonium compounds
(QACs)
Observed IgE adjuvant effect of certain
QACs and combinations of QACs
Biomarkers:
Indoor pool attendance
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Lagerkvist 2004
– Children who regularly attended indoor
pools had significantly lower CC-16 levels
– Might be due to Clara cell damage or
dysfunction
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Carraro 2006
– Children who regularly attended pools 1 to
2 hours/week did not have increase in
fractional exhaled nitric oxide, suggesting
a lack of eosinophilic airway inflammation
Can we answer selected questions
from the 2nd Pepys Workshop?
43. Are underlying host factors more important in
the response to low-level irritant exposures
than to massive accidental exposures?
Host factors modified the effect of low-level
irritant exposures in some studies
33. Biological markers to identify the effects of
irritants on the expression of asthma are
needed
Biological markers for effects of irritants continue
to be explored
Questions
How do the following risk factors for
work-related asthma interact?
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Work-related irritant exposures
Biomarkers (e.g., of epithelial damage)
Atopy
Work-related allergen exposures
Sensitization to workplace allergens
Non-work exposures (ambient air pollution,
at home)
Questions
What proportion of work-related asthma is
due to low-level irritant exposure:
a) alone?
b) in the presence of atopy?
c) combined with allergen exposure?
Questions
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How do we better understand the
combination and temporal
sequence of potential risk factors
for asthma?
Where should we go with
biomarkers for irritants? Which
ones? How to use?