Air Pollutants and Asthma Control

1
Air Pollutants and Asthma Control
www.woolcock.org.au
2
Outcomes Investigated

• Short-term effects on symptoms, lung function and
  AHR (specific and non-specific)
• Chamber studies RCTs
• Panel studies cohort design
• Short-term effects on exacerbations
• ED attendances, hospital admissions, mortality
• Time series
• Long-term effects on asthma incidence, lung
  function
• Ecological studies

3
Pollutants Investigated

• Ozone (oxidants)
• Oxides of nitrogen (mainly NO2)
• Sulphur dioxide
• Particulates (of various sizes)

4
Ozone

• Secondary pollutant
• NOx VOC sun time ozone
• Mainly summer afternoons, outdoor
• Insoluble, highly reactive oxidant
• Respirable to small airways and alveoli

5
Ozone

• Symptoms
• Cough
• Pain on inspiration
• Chest tightness
• Lung function
• Decrease in lung volumes
• Decrease exercise capacity (athletes)
• Possible enhanced response to allergen challenge
  (at high levels)

6
Effect of ozone exposureProportion experiencing
gt 10 decrease in FEV1
50
40
30

6.6
6.6
5.6
5.6
20
4.6
4.6
10
Duration(hrs)
3
3
2
2
0
1
1
0.0
0.08
0.1
0.12
Ozone concentration(ppm)
McDonnell et al., AJRCCM 1995 152589-96
7
Probability of a 10 Fall in FEV1
8
OzoneSummary of Panel Studies (1985 1995)
1
0
Regression coefficient (FEV1 L/ppm)
Mean 0.65 L/ppm
-1
-2
9
OzoneFactors influencing response

• concentration
• duration of exposure
• level of exercise
• Marked inter-individual variability, but
  consistent within individuals

10
OzonePopulation sub-groups

• elite athletes - more responsive
• children less symptoms
• elderly less responsive
• asthma - in general, not different
• COPD - less responsive

11
Effect of Ozone on Allergen Responsiveness
Mild atopic asthma (n15) pre-exposed to FA or O3
0.12ppm x 1 hour
Also no significant effect of O3 pre-exposure on
allergen induced increase in non-specific AHR
P 0.12
12
Effect of Oxidants on Allergen Responsiveness
No effect at half conc for 6 hrs
3 hour exposure
0.2ppm
0.4ppm
13
Effect of Ozone on Post-allergen Sputum Cell
Counts
Mild asthma, dual allergen responders (n 12),
Rx ß2 agonists only
14
Differential Cell Counts
FA
O3
15
Asthma Admissions
16
Ozone and Asthma Admissions Brisbane
17
Ozone Dose-Response 1 hr averages
18
Ozone Dose-Response 8 hr averages
19
OzoneSummary

• Symptoms and decreased lung function
• Dose, duration and exercise dependent
• Athletes most at risk
• Effect in high risk groups not enhanced
• Effect on risk of hospitalisation varies
• Basis of heterogeneity is unknown but may be
  informative

20
Nitrogen Dioxide

• Fossil fuel combustion
• Motor vehicles
• Gas heaters and stoves
• Poorly soluble, highly reactive oxidant
• Reaches small airways

21
Effects of NO2 in People With Asthma

• People with asthma are more sensitive to effects
  on airway narrowing
• Inter-subject variability
• Some enhanced allergen responsiveness at high
  concentrations
• Epidemiological evidence of link with asthma
  symptoms and hospitalisations is conflicting and
  inconclusive
• More evidence for link with symptoms with indoor
  exposure

22
Sydney Air Pollution Study
23
Particulates

• Non-gaseous airborne pollutants
• Heterogeneous
• Size matters
• Composition
• Diesel exhaust particulates modulate immune
  response in the lung
• ? Metals as catalysts
• ? Carrier
• ? Other toxic effect

24
Effect of Particulates on Lung FunctionMeta-analy
sis of Panels of Children
25
ParticulatesSymptoms and lung function
LRT Symptoms
PEF change (L/min)
PM10 Quartiles
Pope and Dockery, 1992
26
ParticulatesEffect on lung function in school
children
0.02
0.01
0.00
-0.01
asthma
Regression coefficient
non-asthma
-0.02
-0.03
-0.04
-0.05
-0.06
Koenig et al., Environ Res 1993 6326-38
27
ParticulatesER visits for asthma
Schwartz, 95
28
Particulates Acute Exposure in People With Asthma

• More symptoms.
• Decrease in lung function.
• Hospital admissions.
• Conflicting evidence negative studies in Europe
  and Sydney.

29
Sulphur Dioxide

• Soluble, irritant gas
• Product of burning sulphurous fossil fuel
• Only point source pollutant in Australia

30
Effects of Sulphur Dioxide

• Potent trigger for bronchoconstriction in people
  with asthma at 0.25 0.5 ppm
• Individual variability in susceptibility
• Very brief exposure required
• Partially blocked by ipratropium and
  indomethacin
• No effect in people without asthma up to 5ppm

31

• SO2 dose response relationship for symptoms in 23
  people with mild asthma when exposed to arrange
  of SO2 concentrations for 5 minutes. Plt0.05.
  Total symptoms score is the aggregate of cough,
  sputum, substernal irritation, wheeze, chest
  tightness, dyspnea, throat irritation, nasal
  discharge/congestion, fatigue, headache, eye
  irritation and any other symptoms. From Linn et
  al., 1983.

32
SO2 dose response relationship for FEV1 in
non-asthmatics, mild and severe asthmatics when
exposed to arrange of SO2 concentrations for 15
minutes. 85 people including 24 non-atopic and
non-asthmatics, 21 atopics, 16 minimal/mild
asthmatics and 24 moderate/severe asthmatics.
(From Linn et al. 1987).
33
Meta-analysis for SO2

• 0.01 ppm increase in SO2.
• Ambient 24 hour levels ranged from 0.004-0.04 ppm
• Hospitalisations of studies OR 95 CIs
• Total 25 1.0229 1.0140-1.0318
• Respiratory 10 1.0202 1.0103-1.0301
• Asthma 10 1.0299 1.0065-1.0538
• Cardiovascular 5 1.0265 1.0024-1.0512
• Mortality
• Total 16 1.0158 1.0066-1.0251
• Respiratory 14 1.0119 0.9994-1.0246
• Cardiovascular 12 1.0095 1.0022-1.0169

34
Conclusion

• Varying relation to asthma
• Heterogeneity in response only partly (and
  loosely) related to asthma status
• Mechanisms not established
• Evidence that more than one may be involved
• Epidemiology is difficult
• Ubiquitous exposure
• Lots of confounders