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PULMONARY FUNCTION TESTING
1718 Jurin J. blew air into a bladder and measured the volume of
air in the bladder by the principles of Archimedes. He
measured 650 ml tidal volume and maximal expiration of
3610 ml.
1749 Bernouilli D. decribes a method of measuring an expired
volume.
1788 Goodwyn E. sucked water into a 'pneumatic vessel' which
was weighted on scales. He stated that the Vital Capacity
could reach as much as 4460 ml. He corrected for
temperature.
1796 Menzies R. plunged a man into water in a hogshead (large
barrel) up to his chin and measured the rise and fall of the
level in the cylinder round the chin. With this method of body
plethysmography he determined the tidal volume.
1800 Davy H. measured his own vital capacity 3110 ml, his tidal
volume 210 ml with a gasometer and the residual volume
590-600 ml by a hydrogen dilution method.
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1845 Vierordt published his book
'Physiologie des Athmens
mit besonderer Rücksicht
auf die Auscheidung der
Kohlensäure'. For his
experiments he used an
'Expirator'. Vierordt already
described some parameters
still used today in modern
spirometry, like residual
volume ('Rückständige
Luft'), vital capacity ('vitales
Atmungsvermögen'), ...
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1852 Hutchinson, John publishes
his paper about his water
spirometer. He recorded the
Vital Capacities of over 4000
persons with his spirometer.
He did three trials and
occluded the nose. He
classified the persons as
'Paupers', 'First Battalion
Grenadier Guards', 'Pugilists
and Wrestlers', 'Giants and
Dwarfs', 'Girls', 'Gentleman',
'Diseased cases'. He showed
the linear relationship of vital
capacity to height and also
showed that that vital
capacity does not relate with
weight at any given height.
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1866 Salter added the kymograph to the spirometer to record time
as well as the volume obtained.
1868
Bert P. introduces the total body plethysmography and did
experiments on animals only, and presented his studies
under the title ['Alterations of the pulmonary air pressure
during the two periods of respiration'].
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1879
Gad J. publishes a paper about the 'Pneumatograph', which
allows to register additionally to the known parameters
resulting from spirometric examination also the volume
changes of the thorax during inspiration and expiration.
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1904 Tissot introduces a close-circuit spirometer.
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1908
Marie Krogh sits next to the respiration chamber constructed
in Greenland. Two Eskimos remained inside the chamber for
four days. Food consumption was monitored, respiratory gas
was analyzed using Krogh's hand-made equipment, and daily
urine samples analyzed for nitrogen content.
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1916
Krogh A. publishes the monograph The Respiratory
Exchange in Animals and Man. Krogh constructed his own
equipment, perfecting the art of glassblowing and other
laboratory skills. Krogh’s experiments led to the Nobel Prize.
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1947
Tiffeneau R. introduces the FEV1 and the Tiffeneau Index
(FEV1/VC).
1959
Wright B.M. and McKerrow C.B. introduces the peak flow
meter.
1969
DuBois A.B. and van de Woestijne K.P. presents the whole
body plethysmograph on humans.
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TYPES OF SPIROMETERS
Volumetric Spirometers
Water bell
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Dry Rolling-Seal
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Flow measuring Spirometers (Laminar flow theory)
•
•
•
•
•
Fleisch-pneumotach
Lilly (screen) pneumotach
Turbine
Pitot tube
Hot-wire anemometer
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SPIROMETRIC TEST STANDARDS
ATS 1994 UPDATE, AM J RESPIR CRIT CARE MED
VOL 152. PP 1107-1136, 1995 (SIMILAR TO 1979 STANDARD)
Equipment
Spiro
Identify manufacturer, model number, type (bellows, water, dryrolling seal, pneumotach etc.).
Vol
0.00 to 7.00 L (BTPS).
Acc
+3% or +50 ml, whichever is greater.
Calib
Minimum 2.00 L syringe with calibration volume displayed on chart.
Graph
Minimum 10mm/L and 20mm/s, volume vs time tracings of 3 best
tests required on graphic report.
Test Information
Temp
Spirometer temperature to nearest oC.
Press
Local barometric pressure to nearest mmHg.
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Test Administration
Tech
Technician administrating the test should have successfully
completed a NIOSH approved course in spirometric testing.
Posture Standing or seated, but same posture for repeat evaluations if
possible.
Nose
Clips
Recommended, or subject can pinch nose.
Test
Minimum Forced Expired Time (FET) of 6 Sec.
Duration
End Of
Test
No volume change for 2 sec or FET of 10 sec.
Quality
Assur
Good initial and continued effort without coughing, glottis closing or
leaks.
Number Minimum of 3 good quality tests, but repeatability (below) may
of Tests require up to 8 good quality tests.
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Calculations
FEV1
Back-extrapolate and report largest & 2nd largest FEV1 in L BTPS.
FVC
Report largest and 2nd largest FVC In L BTPS.
FET
Must be recorded for reported FVC's.
Repeat
ability
Two largest FVC's and FEV1's within 5% or 100 ml, whichever is
greater.
Pred
Values
Can vary by 30% depending on source.
Race
Corr
African-American generally 15% lower Volumes and Flow rates
than Caucasian.
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COMMON & UNCOMMON SPIROMETRIC MEASURES
•
•
•
•
•
•
FVC: Forced Vital Capacity - This is the total amount of air that you can
forcibly blow out after full inspiration, measured in liters.
FEV1: Forced Expiratory Volume in 1 Second - This is the amount of air that
you can forcibly blow out in one second, measured in liters. Along with FVC it
is considered one of the primary indicators of lung function.
FEV1 / FVC - This is the ratio of FEV 1 and FVC, which showing the amount
of the FVC that can be expelled in one second. In healthy adults this should
be approximately 80%.
PEF: Peak Expiratory Flow - This is the speed of the air moving out of your
lungs at the beginning of the expiration, measured in liters per second.
FEF 25-75%: Forced Expiratory Flow 25-75% - This is the average flow (or
speed) of air coming out of the lung during the middle portion of the
expiration (also sometimes referred to as the MMEF, for maximal midexpiratory flow).
FET: Forced Expiratory Time - This measures the length of the expiration in
seconds.
FEV.5, FEV2, FEV3, FEFMAX, FEF25, FEF50, FEF75, FEF75-85, FIF25, FIF50,
FIF75, etc., etc., etc.
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MEASURING THE FEV1, FVC AND FEF25-75 (MMEF)
•
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MEASURING INSTANTANEOUS FLOW RATES FROM A FLOW VOLUME CURVE
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LUNG VOLUME AND CAPACITIES
• The total volume contained in the lung at the end of a maximal inspiration is
subdivided into volumes and subdivided into capacities.
• There are four volume subdivisions which: do not overlap, can not be further
divided, and when added together equal total lung capacity.
• Lung capacities are subdivisions of total volume that include two or more of the
4 basic lung volumes.
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• TLC = RV+IRV+TV+ERV = IC+FRC = VC+RV
• VC =IRV+TV+ERV = IC+ERV = TLC-RV
• FRC = RV+ERV
• IC = TV+IRV
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Measuring Vital Capacity and its subcomponents. Use a spirometer.
Measuring Residual Volume. Cannot be measured by spirometry, and is
determined by one of 3 techniques.
In practice measure FRC, and then subtract ERV to compute RV.
Nitrogen washout technique (open circuit). Poorly ventilated or nonventilated areas will not be included in FRC with this technique.
2500 ml with 80% N2
= 2000 ml N2
40000 ml with 5% N2
= 2000 ml N2 = 2500 ml air
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Helium dilution technique. Poorly ventilated or non-ventilated areas will not be
included as part of FRC when measured with this technique.
Before equilibrium
After equilibrium
Amount of He
= C1 x V1
= C2 x (V1 + V2)
Where: V1 = initial volume of spirometer (known)
V2 = initial volume of airways (usually FRC)
C1 = initial concentration of helium (known)
C2 = final (equilibrium) concentration of helium (known)
Solve for V2 = (C1-C2)/C2 x V1
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Body Plethysmography. Non-ventilated regions are included in FRC as
measured by this technique.
• The subject breathes normally, and at the end of a normal exhalation the
shutter is closed to occlude the airway
• The subject makes inspiratory and expiratory efforts, his alveolar pressure
being recorded using a pressure gauge connected to the airway proximal to the
stopcock.
• The pneumotach measures ΔV of the box less the subject, and thus one
determines ΔV/ΔP, and can calculate TGV.
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• Assuming that the change in volume (ΔV) = 71 ml, and that the change in lung
gas pressure (ΔP) = 20 mmHg, and that Ps = 760 mmHg and Pv = 47 mmHg,
P = Ps – Pv = 713 mm HG, the calculation proceeds as follows:
PV = (P + ΔP)(V - ΔV), where V = Thoracic Gas Volume = FRC
• Multiplying out
PV = PV - PΔV + VΔP - ΔPΔV
• Cancelling out PV’s, rearranging, and factoring
V = ΔV(P + ΔP)/ΔP
• Since ΔP is quite small relative to P (20 mmHg versus 713 mmHg), then
V = ΔV(P)/ΔP
V = 71 ml x (713 mmHg) / 20 mmHg = 2,531 ml = FRC
Radiographic Determination. A qualitative technique. Non-ventilated regions
are included in FRC as measured by this technique.
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Henry Glindmeyer 7/10/08
LUNG CAPACITIES AND RESPIRATORY DISEASES
• Obstructive Disease. Respiratory disease which make it more difficult to get
air out of the lungs (emphysema, chronic bronchitis, asthma). Decreased VC;
increased TLC, RV, FRC. Figure B
• Restrictive Disease makes it more difficult to get air in to the lungs. They
“restrict” inspiration. Includes fibrosis, sarcoidosis, muscular diseases, and
chestwall deformities. Decreased VC; decreased TLC, RV, FRC. Figure C
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•
LUNG VOLUME TEST STANDARDS
ATS/ERS 2005 STANDARDS NO. 3 (Eur Respir J 2005; 26:511-522)
FRC
At least 1 test, but if 2 tests, they should be within 10% of the
larger
SINGLE BREATH DIFFUSING CAPACITY (DLCO) TEST STANDARDS
ATS 1995 UPDATE (AM J RESPIR CRIT CARE MED VOL 152. PP 2185
Insp Vol
> 85% of largest FVC or VC
Insp Time < 4 seconds
BHT
9-11 seconds
Exp Time < 4 seconds
DLCO
At least 2 tests within 10% or 3 units of the larger
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Henry Glindmeyer 7/10/08
SINGLE BREATH DIFFUSING CAPACITY (DLCO)
• Diffusing Capacity measures the transfer of a diffusion-limited gas (Carbon
Monoxide, CO 0.3%) across the alveolocapillary membrane.
• CO combines with hemoglobin approximately 210 times more readily than
oxygen does.
• In the presence of normal amounts of hemoglobin and normal ventilatory
function, the primary limiting factor of diffusion of CO is the status of the
alveolocapillary membrane.
DLCO can be physiologically reduced by
• decrease in the total surface area,
• loss of capillary bed,
• increased distance from terminal bronchiole to alveolocapillary membrane,
• mismatching of ventilation to blood flow.
DLCO can be procedurally altered (reduced) by
• slow inhalation,
• reduced inhaled volume,
• reduced breathhold time,
• reduced washout volume
• reduced sample volume.
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SPIROMETRY QUALITY ASSURANCE AND INTERPRETATION
Examine tracings for
• Initial and continued effort, and adequate expiratory time
Look at the demographic data
• check entered data that is used to determine predicted values
Stick with reliable spirometric parameters
• (FEV1, FVC, FEV1/FVC(%), FEF25-75)
• Select appropriate predicted values
• Be familiar with the lower limit of normal
• Understand the effect of obstructive, restrictive and mixed impairments on
these parameters
Many predicted values
• Are based on all Caucasian white collar populations
• Utilize linear change driven by small numbers of subjects
• The linear regression overestimates lung function of older workers due to
inclusion of very elderly (90+ years) subjects with no symptoms or conditions
whose values tend to flatten the slope
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•
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PREDICTED VALUES
Estimate of normal lung function based on:
• Demographics (age, height, gender, race (occasionally),
weight (occasionally)
• Determined from a population of never-smokers (usually),
absent respiratory symptoms and absent occupational
exposure (sometimes)
• Based on cross-sectional data only, not longitudinal, so
predicted changes with age assume the younger
individuals (say 30 year olds) will have the same lung
function as the older individuals (say the 60 year olds ) as
they age (say 30 years).
• Depend on the equipment and procedures used and the
population tested
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VARIATION IN FEV1 PREDICTED VALUES
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=
%PREDICTED VALUES (Observed/Predicted)x100
AND LOWER LIMIT OF NORMAL
5
4.5
4
3.5
3
100%P
80%P
LLN
FEV1 2.5
2
1.5
1
0.5
0
20 years
30 years
40 years
50 years
60 years
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INDIVIDUAL ASSESSMENT OF LUNG FUNCTION
5
4.5
4
3.5
3
FEV1 2.5
2
100%P
Subject A
Subject B
LLN
1.5
1
0.5
0
20 years
30 years
40 years
50 years
60 years
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Henry Glindmeyer 7/10/08
5
4.5
4
3.5
3
FEV1 2.5
2
100%P
Subject A
Subject B
LLN
1.5
1
0.5
0
20 years
30 years
40 years
50 years
60 years
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Henry Glindmeyer 7/10/08
POPULATION ASSESSMENT
4.8
4.6
4.4
4.2
FEV1
Tests
in
1980
4
3.8
3.6
3.4
3.2
3
20 years
30 years
40 years
50 years
60 years
Population of cigarette smokers
• Initially 30-40 years old
• Greater decline in older subjects with
longer smoking history
• All stop smoking in 1980
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Henry Glindmeyer 7/10/08
4.8
4.6
4.4
4.2
FEV1
Tests
in
1980
4
3.8
Tests
in
2000
3.6
3.4
3.2
3
20 years
30 years
40 years
50 years
60 years
Population retested in 2000
• Now 50-60 year old non-smokers
• Steep cross-sectional age regression persists
• Actual longitudinal decline more normal
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Henry Glindmeyer 7/10/08
4.8
Tests in 1980
4.6
4.4
4.2
FEV1
4
3.8
3.6
3.4
3.2
3
20 years
30 years
40 years
50 years
60 years
Population of never smokers
• initially 30-50 years old
• All start smoking in 1980
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4.8
Tests in 1980
4.6
4.4
4.2
FEV1
4
3.8
3.6
3.4
Tests in 2000
3.2
3
20 years
30 years
40 years
50 years
60 years
Population retested in 2000
• Now 40-60 years old current smokers
• Shallow cross-sectional age regressions persists
• Actual longitudinal decline steeper
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Henry Glindmeyer 7/10/08
Cross-sectional data are:
• Influenced by past respiratory effects
• Relatively insensitive to current effects
Longitudinal data are:
• Relatively insensitive to past respiratory effects
• Influenced by current respiratory effects
Both analyses agree only when:
• Past and current respiratory effects are similar
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CLASSIFICATION OF COPD
• American Thoracic Society (ATS)
• Global Initiative for Chronic Obstructive Lung Disease (GOLD)
• Using data from the U.S. population-based third National Health and Nutrition
Examination Survey (NHANES III),
The following case definitions for COPD and airflow obstruction were used
COPD definitions based on a fixed ratio criteria:
• Mild COPD (GOLD Stage 1): FEV1/FVC<70% and FEV1≥ 80% predicted.
• Moderate COPD (GOLD Stage 2): FEV1/FVC<70% and FEV1<80%
predicted.
LLN-based definitions:
• LLN-1: FEV1/FVC<LLN and FEV1<100% predicted
• LLN-2: FEV1/FVC<LLN and FEV1<LLN (about 80% predicted).
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Figure 1 Predicted lower 95% confidence limits (LLN) for FEV1/FVC (%), for
males, by race/ethnicity, based on NHANES III data
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50
Prevalence (%)
40
Mild COPD
Moderate COPD
LLN-1
LLN-2
30
20
10
0
20 to 29
30 to 39
40 to 49
50 to 59
60 to 69
70 to 80
Age Group
Figure 2 U.S. age-specific prevalences of airflow obstruction based on the
following definitions: LLN-1, LLN-2, Mild COPD and Moderate COPD, as
estimated from NHANES III data
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30
Prevalence (%)
25
Mild COPD
Moderate COPD
LLN-1
LLN-2
20
15
10
5
0
20 to 29
30 to 39
40 to 49
50 to 59
60 to 69
70 to 80
Age Group
Figure 3 U.S. age-specific prevalences of airflow obstruction based on the
following definitions: LLN-1, LLN-2, Mild COPD and Moderate COPD, as
estimated from never-smokers without respiratory disease or conditions
from NHANES III data
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14
12
Prevalence (%)
10
LLN-2
Asthma
Emphysema
Chronic Bronchitis
CB Symptoms
8
6
4
2
0
20 to 29
30 to 39
40 to 49
50 to 59
60 to 69
70 to 80
Age Group
Figure 4 U.S. age-specific prevalence of airflow obstruction based on LLN2, physician-diagnosed asthma, emphysema, chronic bronchitis, and selfreported symptoms of chronic bronchitis (CB), estimated from NHANES III
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70
60
Prevalence (%)
50
No Disease
Asthma
Emphysema
Chronic Bronchitis
CB Symptoms
40
30
20
10
0
20 to 29
30 to 39
40 to 49
50 to 59
60 to 69
70 to 80
Age Group
Figure 5 Percent with airflow obstruction (LLN-2) among individuals with
physician-diagnosed emphysema, chronic bronchitis and asthma; among
those who do not report physician-diagnosed disease (no disease); and
among those reporting symptoms of chronic bronchitis (CB), NHANES III
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Definitions for COPD based on a fixed ratio of FEV1/FVC<0.70 will result in
• Underestimation of the presence of airflow obstruction among persons 20-49
years of age and
• overestimation in persons over age 50.
• These misclassification rates have important implications for case-finding
and for estimating the burden of disease and need to be taken into
consideration when applying the COPD definitions in practice.
In comparison to the FEV1/FVC<LLN and FEV1<100% predicted definition
(LLN-1), the fixed ratio-based definition for mild COPD
• underestimates airflow obstruction by 29% in 20-49 year olds and
• overestimates it by 58% in 50-80 year olds.
In comparison to the FEV1/FVC<LLN and FEV1<LLN definition (LLN-2), the
fixed ratio-based definition for moderate COPD
• underestimates airflow obstruction by 31% in 20-49 year olds and
• overestimates it by 37% in 50-80 year olds.
Approximately 0.9 million (26%) of the 3.6 million U.S. adults aged 20-49
years who have airflow obstruction (FEV1/FVC<LLN and FEV1<LLN
definition) may have undiagnosed respiratory disease.
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YEAR-TO-YEAR CHANGES IN FEV1
• Often made in spirometry monitoring programs to identify individuals with an
excessive decline.
• The American Thoracic Society (ATS) recommends that the year-to-year
decline in FEV1 that exceeds 15% should be considered clinically important
• The American College of Occupational and Environmental Medicine
(ACOEM) has proposed a limit for a significant decline based on the ATS
recommendations.
We used data from four spirometry monitoring programs with varying data
precision
• Evaluated the longitudinal data precision using the pair-wise estimate of
within-person variation.
• We then estimated the appropriate program-specific absolute and relative
Longitudinal Limit of Normal Decline (LND)
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800
Limit of Normal Decline and
th
5 Percentile for FEV1 (mL/yr)
700
1 yr
600
P3B
P3B
500
P3B
P2
400
P3A
P2
P2
P4
P3A
P1
300
P4
P4
2 yr
P3A
P1
3 yr
200
P1
5 yr
8 yr
100
15 yr
0
100
150
200
250
Within-person Standard Deviation (mL)
Male
Female
Overall
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Henry Glindmeyer 7/10/08
CONCLUSIONS:
The expected rate of normal decline in FEV1 is about 30 ml/yr.
• Actually a slight increase from age 20-30, a plateau from 30-40 and
a decline thereafter.
Depending on individual variability, the variability of the testing program,
and the length of follow-up:
• For three data points over 2 years, individual declines would need to
exceed 200-300 ml/yr before they could be considered abnormal
• With 5 years of follow-up, a reasonably good surveillance program
could consider individual declines in excess of 100 ml/yr excessive.
• Greater declines would need to be observed in individuals with
inherently variable lung function, like asthmatics
• Tracking the variability allows the program to become aware of and
minimize non-physiologic sources of variability (equipment,
calibration, technicians, procedures, etc.)
56