1. The patient is a 64-year-old obese female with a history of hypertension, diabetes, heart disease, COPD, and congestive heart failure who presents with dyspnea on exertion. 2. Pulmonary function tests show an FEV1 of 34% predicted indicating severe COPD. Spirometry also found an increased RV and decreased DLCO. 3. Ventilatory limitation during exercise is characterized by an inability to further increase minute ventilation due to constraints of ventilatory mechanics. This leads to respiratory acidosis and limits exercise capacity before maximal cardiac output is reached, causing the patient to stop due to dyspnea rather than fatigue.

1. Ventilatory Limitation and Role
of Flow-Volume Loops in CPET
Gagan Kumar MD
Fellow
Pulmonary & Critical Care

2. Case
• 64 y obese female c/o “Dyspnea on exertion”
• PMH: HTN, DM, Hyperlipidemia, CAD (s/p 3V
CABG in 2010), COPD, CHF.
• Last ECHO shows EF 25% with moderate diastolic
dysfunction.
• 40 pack years smoking.
• Medications: metoprolol, amlodipine, albuterol,
simvastatin

3. Case
• PFTs:
– Ratio = 60
– FEV1 =1.1 L (34%),
– TLC = 106%,
– RV = 120%,
– DLco = 50%
• BMI 35

5. Stopped due to ‘Dyspnea’

6. What is the reason for dyspnea of
exertion?
1.
2.
3.
4.
5.
6.
Deconditioning
Obesity
COPD
CHF
Pulmonary hypertension
Interstitial lung disease

7. Features of ventilatory limitation
• The VO2max is reduced relative to
age, sex and height-matched
normal individuals.
• Heart rate rises with exercise but
because ventilatory failure occurs
before the heart is stressed to its
maximum
• At any given work rate:
– minute ventilation is higher than
normal, as the result of increased
dead-space ventilation.

8. Features of ventilatory limitation
• At peak exercise:
– Minute ventilation is at or just below
their MVV indicating that they have
no ventilatory reserve.
– Instead of the expected decrease in
arterial PCO2 with maximal exercise,
obstructive lung disease patients will
develop a respiratory acidosis
because they cannot ventilate
enough to eliminate the CO2 being
produced in exercising muscles.

9. Features of ventilatory limitation
• Because ventilatory mechanics limit the person
before the heart reaches its limits, they never
reach a point where the heart cannot meet the
blood flow demands of the exercising muscle 
significant lactic acidosis does not develop and
you cannot identify a ventilatory threshold.
• Oxygen saturation may fall due to areas of low
V/Q inequality.
• These patients stop exercising due to “dyspnea”.

10. Respiratory limitation and Role of
flow-volume loops in CPET

11. Minute ventilation (ṼE)
• In healthy person (ṼEmax)
– At rest: 5-10LPM
– During exercise in untrained person ~ 100LPM
– During exercise in trained person ~ 200LPM

12. Maximum minute ventilation
during exercise : ṼEmax
• Ventilation increases linearly
with work load
• When work reaches ~ 60% of
VO2max  metabolic
demands > capacity of
aerobic metabolism
• Anerobic metabolism ensues
– lactic acid is produced
– Buffering by HCO3 
increase in VCO2

13. ṼEmax
Ventilatory reserve
(>20-30%)
ṼEmax
Ventilatory reserve
decreases in:
1. COPD
2. CHF
3. ILD
4. Obesity
5. Pulmonary vascular
disease
6. Deconditioning

14. Ventilatory reserve
• Also called ‘breathing reserve’
• Ventilatory reserve = [1- (ṼEmax/MVV)]X 100
• Normal 20-30%
• Absolute difference should be > 10-15LPM

15. How do we calculate MVV?
• Maximum voluntary ventilation
– Indirect MVV: FEV1 x 40 (some use 35)
– Direct MVV: maximal breaths for 12 sec then multiply
by 5 to get MVV.
• Healthy persons use <70% of MVV during
maximal exertion. In diseased this exceeds 80%.
• In absolute terms if maximal ventilation reaches
within 10-15L/min of MVV, ventilatory limitation
is probably present.

16. MVV vs. Exercise hyperpnea
• During exercise: End Expiratory Lung Volume (EELV) is reduced
resulting in tidal breathing occurring at a more optimal position of
the pressure volume relationship of the lung and chest wall with
consequent less work of breathing

17. Limitation of MVV
– MVV is performed at high lung volumes
– Expiratory flows reach maximum at the
highest lung volumes
– Requires large expiratory pleural
pressures to obtain the high flows early in
expiration (often two to three times those
necessary to produce maximal flows)
– Actually it requires lot of work since you
are working at high EILV/TLC = high
elastic load
– Hence MVV cannot be carried out for >15
to 30 s
– Motivationally dependent
– Ventilatory capacity may also vary during
exercise due to
• bronchodilation
• bronchoconstriction

18. Tidal volumes (VT)
• For low to moderate
workloads
– increase in VT accounts for
most of the rise in
ventilation
– Increased frequency
contributes small amount
• When VT approaches 5060% of VC
– Frequency is major
contributor

19. VT
• In restrictive disease,
VT may be relatively
fixed. The increase in
ṼE is primarily by
increase RR.

20. VT
• Increase in VT is done by
– Utilizing IRV
– Reducing EELV

21. Dead Space: Tidal volume ratio
(VD/VT)
• With exercise
– Decreases rapidly at onset
– Then more slowly
• There is decrease in dead space due to better
VQ matching and increasing tidal volumes
– <0.45 at rest
– <0.3 during maximal exercise

22. VD/VT
• Marker for pulmonary vascular disease or
interstitial lung disease
• NORMAL in Obesity & deconditioning !!

23. Anaerobic Threshold
• Between 45-60% estimated VO2max for the person
• Anaerobic metabolism ensues
– Lactic acid is produced
– Buffering by HCO3  increase in VCO2
– Increased ṼE due to increase in VCO2

24. Respiratory exchange ratio
• = ṼCO2/ṼO2
• In a steady state = respiratory
quotient = 0.8
• Hyperventilation before
exercise  increases it
• Comes to baseline and starts
rising slowly
• Once VCO2 exceeds VO2 : RER
crosses 1
• If >1.15  shows maximal
effort was performed

25. Respiratory exchange ratio
• RQ = 1 for carbohydrates
• RQ < 1 indicates carbohydrate + fat (RQ=0.7) +
protein (RQ=0.8) metabolism
• RQ is reserved for events at cellular & tissue
level.

26. Respiratory exchange ratio
• Ventilatory equivalent method:

27. Respiratory exchange ratio
• V slope method

28. Ventilatory equivalent for CO2
ṼE/VCO2
• In initial portion both ṼE and VCO2
change linearly till anaerobic
threshold
• Once this is reached, both increase
at faster rate as lactic acid is
buffered by HCO3 to produce more
CO2
• Once buffering cannot keep pace
with metabolic acidemia  ṼE
increases out of proportion to VCO2
and the slope goes upwards

29. Ventilatory equivalent for CO2
ṼE/VCO2
• Rest: 25-30L/L
• High values are a marker
of inefficient ventilation,
which can be due to
– Hyperventilation
– Increased dead space.

30. ṼE/VCO2 at Anaerobic threshold
• Normal <34 L/L
• “Non invasive index of dead space” = Adequate
ventilation with poor perfusion.
• Increased in
–
–
–
–
CHF
COPD
ILD
Pulmonary Vascular Dz
(if > 60 = severe)
• NORMAL in
– Obesity
– Deconditioning

31. Ventilatory equivalent for O2
ṼE/VO2
• Measure of “Efficiency of
ventilatory pump”
• Normal
• At rest: 30 L/L
• Pre exercise hyperventilation
increases it.
• Decreases to 25L/L with exercise
due to better VQ matching
• Increases once the person
reaches their ventilatory
threshold (ṼE follows increased
CO2 production)

32. ṼE/VO2
• High values are a marker of “Inefficient
ventilation”
• Seen in
– Hyperventilation
– Increased dead-space
– Poor gas exchange

33. Flow volume Loop Analysis
MFVL = Maximal Flow Volume Loop
extFVL = Exercise Tidal Flow Volume Loop
VT= Tidal Volume
EELV=End expiratory Lung Volume
EILV = End Inspiratory Lung Volume
VT = Tidal volumes
ERV = expiratory reserve volume
IRV = Inspiratory reserve volume
IC – Inspiratory capacity

34. Flow volume Loop Analysis

35. Some new terms
• End-expiratory lung volume : EELV
• Breathing at a low lung volume (near RV) limits the
– Available ventilatory reserve due to the shape of the
expiratory flow-volume curve
– The reduced maximal available airflows
– Reduced chest Wall compliance.

36. Some new terms
• End-inspiratory lung volume: EILV
• breathing at high lung volumes (near TLC)
– Increases the inspiratory elastic load  work of
breathing

37. What is Expiratory Flow Limitation
• Percent of VT that
meets/exceeds
expiratory boundary
of MFVL

38. Functional Residual Capacity
• FRC is the lung volume
achieved with a passive
expiration and is an
equilibrium volume
between the chest wall
forces expanding the lungs
and the recoil forces of the
lungs

39. End-expiratory lung volume
• Dynamically determined (dynamic FRC) based on
expiratory and inspiratory muscle recruitment and
timing.
• Why should you drop your EELV during exercise
– Requires expiratory muscle recruitment : optimize
inspiratory muscle length
– Energy stored (elastic and gravitational energy) in the
chest wall (rib cage, abdomen, and diaphragm) because of
active expiration provides passive recoil at the initiation of
the ensuing inspiration
• If drop in EELV that is too great
– will cause expiratory-flow limitation near EELV due to the
fall in maximal available air flow as lung volume decreases.

40. End-expiratory lung volume
In Normal subjects
• EELV decreases with
exercise
• Expiratory airflow limitation
generally averages , 25% of
the VT at peak exercise
workloads
• Flow limitation occurs only
over the lower lung
volumes, near EELV.

41. End-expiratory lung volume
• EELV increases (to resting values or higher (dynamic hyperinflation) if
– degree of expiratory airflow limitation becomes significant (> 40 to 50%
of the tidal breath), e.g. with heavier exercise
• Increase in EELV causes
– Decreases inspiratory muscle length
– Increases the work and oxygen cost of breathing
– Decreases inspiratory muscle endurance time.

42. End-inspiratory lung volume
• The lung volume at the end of a
tidal inspiratory breath and is
usually expressed as a percent of
the TLC (EILV/TLC) or FVC (if TLC
not available)
• EILV reaches 75 to 90% of TLC in
heavy exercise in normal
subjects.
• As EILV approaches TLC  lung
compliance begins to fall the
inspiratory elastic load
increases.

43. End-inspiratory lung volume
• A high EILV (>90%) relative
to TLC may also be a marker
of ventilatory constraint
and an index of increased
ventilatory muscle

44. When ventilatory demand increases
• Subject increases EELV in order to avoid expiratory
flow limitation and to take advantage of the higher
available maximal expiratory airflows
• EILV increases in order to preserve the exercise VT.

45. End-inspiratory lung volume
• A failure to increase EILV in the presence of
significant expiratory flow limitation
represents
– Inspiratory muscle fatigue
– Inspiratory muscle weakness
– Coexistent elastic loading due to increased lung
recoil
– Constraints imposed by the chest wall

46. End-inspiratory lung volume
• If EILV doesn’t increases as required,
Respiratory Rate goes up.
– Initially it works to decrease work of breathing,
decrease intrathoracic pressures and unpleasant
sensation of breathing at higher flow rates.
– But later this increases expiratory flow limitation

47. Inspiratory flow
• Maximum inspiratory flow: limited mainly by
the ability of the inspiratory muscles to
develop pressure.
• Hence it is marker for inspiratory muscle
constraint.
• This decreases with
– Higher lung volumes (shorter muscle length)
– Higher flow rates (increased velocity of muscle
shortening)

48. Inspiratory flow
• Ability to reduce inspiratory pressure
decreases from 0.65 to 0.97% for every 1%
increase in lung volume above FRC
• Ability to reduce inspiratory pressure
decreases from 4 to 5% for every 1 L/s
increase in inspiratory flow rate above resting.

49. Inspiratory flow reserve
• At the lower ventilatory demands : significant reserve
is observed throughout inspiration
• With higher ventilatory demands: tidal inspiratory
flows come closest to capacity

50. Inspiratory flow reserve
• In normal subjects:
• Flows during exercise typically reach 50 to 70% of
the maximal volitional inspiratory flows at the
closest point during the inspiratory cycle
 so there is no inspiratory flow limitation.
• Low inspiratory flow reserve suggests
1. Inspiratory muscle fatigue
2. Laryngeal dysfunction
3. Poor patient effort

51. Back to MVV
• We talked about limitations of using MVV
• The breathing reserve using the MVV
therefore only provides limited information
and does not provide insight on
– breathing strategy or
– the degree of expiratory or inspiratory flow
constraints.

52. Ventilatory capacity (VECAP)
• Calculates a theoretical maximal exercise
ventilation based on the maximal available
inspiratory and expiratory airflows over the
range of the tidal exercise breath placed at the
measured EELV
• Hence - independent of “volitional effort “
• But is better than MVV since it takes into
account – breathing pattern & dynamic
changes in airway function

53. How to measure VECAP
• Exercise Tidal FVL is aligned within
the MFVL according to the measured
EELV.
• The tidal breath is divided into 50
equal volume segments(ΔV)
• Expiratory time (TE) is determined by
dividing each ΔV by the average
maximal expiratory flow (MEF)
within each volume segment
• Total Expiratory time = ΣTE
• Measure inspiratory to total
breathing cycle time  inspiratory
time
• Expiratory + Inspiratory time 
maximal breathing frequency
• Frequency X VT = ventilatory
capacity

54. VECAP
• In normal subjects:
– Ventilatory capacity decreases with low level of
exercise – due to decrease in EELV
– Then increase as VT increases when it encroaches
inspiratory reserve volume
• No flow limitation exists if tidal expiratory flows
do not meet or exceed the maximal available
flows at any point throughout expiration

55. Limitation of VECAP
• Dependent on accurate measurement of EELV

56. Assessing ventilatory constraints using
Exercise Tidal Flow Volume Lop
(extFVL)

57. Degree of constraint
• < 25% is normal
• As the degree of expiratory flow limitation increases,
EELV typically rises (dynamic hyperinflation) and the
inspiratory elastic load increases.
• The degree of constraint necessary to influence
exercise performance or contribute to the sensation of
dyspnea is unclear.
• Oxygen cost associated with breathing during exercise
rises dramatically as ventilatory constraints are
approached

58. Examples

59. Average fitness
• Flow limitation is present near
peak exercise but over <20% of
the tidal breath and only near
EELV.
• EELV falls by approximately 0.7 L
• EILV can increase up to 80% of
the TLC
• Exercise VE = 68% (of MVV)

60. Healthy aged
• Flow limitation begins to occur at a
lower ventilation than noted in the
younger subjects
• At peak exercise >50% of the tidal breath
meets or exceeds the expiratory
boundary of the MFVL.
• EELV initially decreases but then begins
to increase with these moderate VE
demands
• At peak exercise, EELV is above the
resting FRC
• EILV reaches >90% of TLC,
• Inspiratory flows approach >90% of the
inspiratory flow capacity, indicating little
reserve available to increase VE and
moderate to severe ventilatory
constraint.

61. Endurance athlete
• The responses are similar to the average
fit adult up to a ventilation of ~ 110 to
120 L/min
• With heavier exercise and the increased
ventilatory demands, expiratory flow
limitation increases to >50% of the VT
• EILV approaches >85% of the TLC
• Inspiratory flow rates with exercise are
closest in proximity to the maximal
available inspiratory flow rates at 75%
of TLC reaching 6.0 L/s and 95% of the
available flow.

62. Moderate COPD
• EELV may increase even with
light activity due to the early
degree of expiratory flow
limitation
• By peak exercise, flow
limitation is present over the
entirety of expiration
• Inspiratory flows are produced
that nearly overlap the maximal
inspiratory flows achieved
immediately after exercise.
• EILV approaches >95% of TLC.

63. Interstitial lung disease
•
•
•
Reduced VC and EELV at rest - little room for an exercise-induced decline in EELV
More dependent on an increase in breathing frequency (and flow) to increase
ventilation.
In those patients stopping exercise due to dyspnea
– significant expiratory flow limitation
– high EILV/TLC is present,
•
In patients stopping exercise due to a complaint of leg
– No flow limitation was observed

64. Quick Comparison of FVLs

65. Congestive heart failure
• Patients breathe at
reduced lung volumes
– secondary to increased
respiratory drive and
activation of expiratory
muscles, or due to
inspiratory muscle
weakness.
• Expiratory flow constraint

66. Obesity
• Breathe at extremely low lung
volumes at rest
• During exercise despite
significant room in the
inspiratory reserve volume
there is substantial expiratory
flow limitation
• Even though there is
ventilatory reserve (VE/MVV),
there is little room to increase
the expiratory flow.
NORMAL

67. Obesity

68. 7 Steps to interpret
ventilatory & flow limitations

69. STEP1
• Check resting ventilation ~ 5-10LPM.
• If not Why?

70. STEP 2
• Did MV increase appropriately with work
load?
• Remember – MV increases linearly with work
load till AT then the slope increases a bit

71. STEP 3
• Was VEmax<70% of MVV or expected MVV?
• Was absolute difference >10-15LPM?
• If yes  ventilatory reserve is present
• If not  ventilatory limitation is unlikely

72. STEP 4
• Did VT increase to 50-60% of VC?
• If not  why?
• Was increased RR primarily responsible for
increased VE?
– If yes  suspect restrictive ventilatory pattern

73. STEP 5
• Is there a flow limitation ?
• Is it expiratory, inspiratory or both?
• To what extent?
• Remember: these can be present even if
VEmax<70% of MVV

74. STEP 6
• Did VD/VT decrease appropriately?
• If not  increased dead space ventilation or
inability to increase VT
• You can also look at ṼE/VCO2 at Anaerobic
threshold which can be > 34L/L

75. STEP 7
• What was the reason to stop exercise?
– Chest pain
– Dyspnea
– Leg fatigue
• Was this consistent with the pattern of
ventilation observed?

76. Thank you

77. References
•
‘Manual of Pulmonary function test’ by Gregg Ruppel, 8th edition, Mosby
Publisher.
•
Ofir D, Laveneziana P, Webb KA, O'Donnell DE. Ventilatory and perceptual
responses to cycle exercise in obese women. J Appl Physiol. 2007 Jun;102(6):221726.
•
Johnson BD, Weisman IM, Zeballos RJ, Beck KC. Emerging concepts in the
evaluation of ventilatory limitation during exercise: the exercise tidal flow-volume
loop.Chest. 1999 Aug;116(2):488-503
•
ATS/ACCP Statement on cardiopulmonary exercise testing. American Thoracic
Society; American College of Chest Physicians. Am J Respir Crit Care Med. 2003 Jan
15;167(2):211-77
•
K Albouaini, M Egred, A Alahmar, et al. Cardiopulmonary exercise testing and its
Application. Heart 2007 93: 1285-1292