Role of flow volume loops in cpet

Ventilatory Limitation and Role of Flow-Volume Loops in CPET

Gagan Kumar MDFellow

Pulmonary & Critical Care

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

Case

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

• BMI 35

Stopped due to ‘Dyspnea’

What is the reason for dyspnea of exertion?

1. Deconditioning2. Obesity3. COPD4. CHF5. Pulmonary hypertension6. Interstitial lung disease

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.

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.

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”.

Respiratory limitation and Role of flow-volume loops in CPET

Minute ventilation (ṼE)

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

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

ṼEmax

Ventilatory reserve (>20-30%)

ṼEmax

Ventilatory reserve decreases in:1. COPD2. CHF3. ILD4. Obesity5. Pulmonary vascular

disease6. Deconditioning

Ventilatory reserve

• Also called ‘breathing reserve’• Ventilatory reserve = [1- (ṼEmax/MVV)]X 100

• Normal 20-30%• Absolute difference should be > 10-15LPM

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.

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

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

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 50-60% of VC– Frequency is major

contributor

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

VT

VT

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

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

VD/VT

• Marker for pulmonary vascular disease or interstitial lung disease

• NORMAL in Obesity & deconditioning !!

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

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

• 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.

Respiratory exchange ratio

• Ventilatory equivalent method:

Respiratory exchange ratio

• V slope method

Respiratory exchange ratio

• 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

Ventilatory equivalent for CO2

ṼE/VCO2

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.

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

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)

ṼE/VO2

• High values are a marker of “Inefficient ventilation”

• Seen in – Hyperventilation– Increased dead-space– Poor gas exchange

Flow volume Loop Analysis

MFVL = Maximal Flow Volume LoopextFVL = Exercise Tidal Flow Volume LoopVT= Tidal VolumeEELV=End expiratory Lung VolumeEILV = End Inspiratory Lung VolumeVT = Tidal volumesERV = expiratory reserve volumeIRV = Inspiratory reserve volumeIC – Inspiratory capacity

Flow volume Loop Analysis

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.

• End-inspiratory lung volume: EILV • breathing at high lung volumes (near TLC) – Increases the inspiratory elastic load work of

breathing

Some new terms

What is Expiratory Flow Limitation

• Percent of VT that meets/exceeds expiratory boundary of MFVL

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

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.

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.

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.

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.

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

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.

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

• 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

End-inspiratory lung volume

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)

• 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.

Inspiratory flow

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

• 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 suggests1. Inspiratory muscle fatigue2. Laryngeal dysfunction 3. Poor patient effort

Inspiratory flow reserve

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.

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

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

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

Limitation of VECAP

• Dependent on accurate measurement of EELV

Assessing ventilatory constraints using Exercise Tidal Flow Volume

Lop (extFVL)

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

Examples

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)

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.

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.

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.

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

Quick Comparison of FVLs

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

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

Obesity

7 Steps to interpret ventilatory & flow limitations

STEP1

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

STEP 2

• Did MV increase appropriately with work load?

• Remember – MV increases linearly with work load till AT then the slope increases a bit

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

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

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

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

STEP 7

• What was the reason to stop exercise?– Chest pain– Dyspnea– Leg fatigue

• Was this consistent with the pattern of ventilation observed?

Thank you

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):2217-26.

• 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