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Spirometry, assessment of
bronchial responsiveness and
induced sputum
Catherine Lemière MD,MSc
Hôpital du Sacré-Cœur
de Montréal Université
de Montréal
Spirometry
Flow-volume loop
Normal Airflow limitation
Reversible airflow limitation
Gender: For a given height and age, males have a larger FEV1, FVC, FEF25-75%
and PEF, but a slightly lower FEV1/FVC%.
Age: FEV1, FVC, FEF25-75% and PEF increase, while FEV1/FVC% decreases, with
age until about 20 years old in females and 25 years in males.
After this, all indices gradually fall, although the precise rate of decline is
probably masked due to the complex interrelationship between age and
height. The fall in FEV1/FVC% with age in adults is due to the greater decline
in FEV1 than FVC.
Height: All indices other than FEV1/FVC% increase with standing height.
Ethnic Caucasians have the largest FEV1 and FVC and, of the various ethnic
Origin: groups, Polynesians are among the lowest. The values for black Africans are
10-15% lower than for Caucasians of similar age, sex and height because for
a given standing height their thorax is shorter. Chinese have been found to
have an FVC about 20% lower and Indians about 10% lower than matched
Caucasians. There is little difference in PEF between ethnic groups.
Spirometry Cont’d
• Airflow limitation (FEV1/VC <70%) is considered
reversible if there is an improvement in FEV1 of at
least 12% with an absolute increase of 180ml after
bronchodilator.
• If there is a history suggestive of asthma with
normal spirometry or absence of reversibility a
methacholine challenge should be performed.
Assessing airway responsiveness
Methacholine Challenge
• Methacholine induces a bronchoconstriction
by acting on the airway smooth muscle.
• Methacholine inhalation challenge test
measures the level of airway responsiveness.
Methacholine Challenge
• Administration of increasing doses of
methacholine via a Wright nebulizer (or
dosimeter) until the occurrence of a 20% fall
in FEV1.
• Determination of the provocative
concentration inducing a 20% fall in FEV1
(PC20).
Wright nebulizer
• 2 minutes of nebulization at tidal voulme
• Doubling doses of methacholine
– .03, .06, .125, .25, .50, 1, 2, 4, 8,16 ( 32, 64, 128)
mg/ml
– Measure the FEV1 at about 30 and 90 s after the
end of nebulization. Obtain an acceptable-quality
FEV1 at each time point. This may require
repeated attempts.
– At each dose, report the highest FEV 1
Determining starting dose of methacholine
Hospital Outside
No history of asthma –No treatment
Si FEV1> 75% predicted and FEV1 fall < 10% post-diluant 2 mg/ml 0.5 mg/ml
If FEV1 pred < 75% and FEV1 fall < 10% post-diluant 0.125 mg/ml 0.03 mg/ml
FEV1 fall > 10% post-diluant 0.03 mg/ml No
History of asthma No treatment
If FEV1> 75% predicted and FEV1 fall < 10% post-diluant 0.5 mg/ml 0.03 mg/ml
If FEV1 pred < 75% and FEV1 fall < 10% post-diluant 0.125 mg/ml 0.03 mg/ml
FEV1 fall > 10% post-diluant 0.03 mg/ml No
History of asthma- Treatment for asthma
If FEV1> 75% predicted and FEV1 fall < 10% post-diluant 0.125 mg/ml 0.03 mg/ml
If FEV1 pred < 75% and FEV1 fall < 10% post-diluant 0.03 mg/ml 0.03 mg/ml
If FEV1 fall > 10% post-diluant 0.03 mg/ml No
Methacholine Challenge Test
PC20
Normal > 16 mg/ml
borderline 4-16
Mild 1-4
Moderate to severe<1
Contraindications for methacholine challenge testing
Absolute:
•Severe airflow limitation (FEV1 <50% predicted or <1.0 L)
•Heart attack or stroke in last 3 months
•Uncontrolled hypertension, systolic BP >200, or diastolic BP>100
•Known aortic aneurysm
Relative:
•Moderate airflow limitation (FEV1< 60% predicted or <1.5 L)
•Inability to perform acceptable-quality spirometry
•Pregnancy
•Nursing mothers
•Current use of cholinesterase inhibitor medication (for myasthenia
gravis)
Factor Minimum Time Interval
from Last Dose .
Short-acting inhaled bronchodilators,
such as isoproterenol, 8h
isoetharine, metaproterenol, albuterol, or terbutaline
Medium-acting bronchodilators such as ipratropium 24 h
Long-acting inhaled bronchodilators, such as salmeterol, 48 h
formoterol, tiotropium (perhaps 1 wk for tiotropium)
Oral bronchodilators
Liquid theophylline 12 h
Intermediate-acting theophyllines 24 h
Long-acting theophyllines 48 h
Standard b2-agonist tablets 12 h
Long-actingb2 agonist tablets 24 h
Cromolyn sodium 8h
Nedocromil 48 h
Hydroxazine, cetirizine 3d
Leukotriene modifiers 24 h
Coffee, tea, cola drinks, chocolate Day of study
PC20 measurements in addition to PEF monitoring
SIC – false negative- Monitoring of PC20
Follow-up
Sputum Induction and processing
Sputum induction
• Induction
– Bronchodilation
– 3 seven-minute periods of nebulisation with
increasing concentrations of hypertonic saline (3,
4 and 5%) using an ultrasonic nebuliser.
– Monitoring of FEV1 before each increasing
concentration of hypertonic saline
Sputum Induction
• Sputum collection after each period of nebulization.
• Sample processing within 2 hours after sputum
collection.
Processing
Supernatant
•.
PBS
…
. Centrifuge
Selection .
DTT .
…
..
..
.
Total cell count -Viability
Differential cell Cytospin
count
Induced Sputum
• Normal Values
– Total cell count < 5.5x106/ml
– Neutrophils 15- 64%
– Eosinophils ≤1%
– Macrophages: 30- 80%
– Lymphocytes <3%
– Viability> 40%
– Squamous contamination < 20%
Advantages
• Reproducible
• Sensitive
• Non-invasive
• Measurement of cell counts as well as soluble
inflammatory mediators.
Advantages
• Eosnophils are increased in the majority of
asthmatic subjects.
• Increase after inhalation challenge to common
allergens and decrease after asthma treatment.
• Managing asthma treatment according to sputum
eosinophils seems to reduce asthma exacerbations
in moderate to severe asthmatics.
Green et al. Lancet 2002 360: 1715-21
Sensitivity and specificity of different diagnostic
strategies compared to SIC
1
0.9
0.8
PEF
0.7
PEF/Sputum (1% cutoff)
0.6
PEF/sputum (2% cutoff)
0.5
0.4
0.3
0.2
0.1
0
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1
1- Specificity
(Girard et al, ARJCCM 2004)
Limitations
• Some subjects do not produce enough sputum
(Success rate 70 to 80%).
• Repeated sputum inductions (within 24h) modify cell
counts (increase neutrophils).
