Inncor Lung Clearance Index Method Guide Rev 4 Nov 2018

Innocor® Lung Clearance Index Method

Innovision

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LUNG CLEARANCE INDEX METHOD

1.1

SCOPE

The purpose of this document is to give an introduction to the Lung Clearance Index (LCI) Method used in Innocor. This section applies to users of Innocor with only limited experience in LCI measurements. This document will enable the reader to understand the LCI parameters measured by Innocor and the way they are determined. For more detailed information about the LCI method, please contact Innovision ApS or consult the “Pulmonary Function testing in Preschool Children” in: Am J Respir Crit Care Med Vol 175. pp 1328-1333

1.2

Section 7 – The Multiple-Breath Inert Gas washout Technique of An Official American Thoracic Society / European Respiratory Society Statement: Pulmonary Function testing in Preschool Children.

INTRODUCTION

LCI is a physiological test that measures ventilation distribution in the lungs and the Functional Residual Capacity. Spirometry is the commonest means of assessing lung function where diseases causing obstruction of larger airways eventually result in reduced expiratory flows and volumes. However, spirometry measurements are often normal in the early stages of peripheral airway diseases, and therefore changes (obstruction or restriction) in the peripheral airways associated with early cystic fibrosis disease, early chronic obstructive pulmonary disease or mild asthma cannot be detected by spirometry until the disease has progressed considerably because the small airways only contribute very little to the total airway resistance. Peripheral airway diseases do, however, affect the way air mixes within the lungs and thus lead to increased ventilation inhomogeneity. Ventilation inhomogeneity may be assessed using the multiplebreath washout (MBW) test performed by washing out a previously washed-in tracer gas from the lungs during tidal breathing of room air. From this test Lung Clearance Index (LCI) can be determined as a sensitive marker of airway disease. It reflects differences in specific ventilation between well and poorly ventilated lung regions. The LCI manoeuvre starts with normal tidal breathing during an Inert gas rebreathing (IGR) for rapid wash-in of a small amount of SF6. When an even concentration is obtained in the lungs the subject is disconnected from the bag and the multiple-breath washout starts. The subject breathes room air until the end-tidal SF6 concentration has fallen below 1/40th of the starting concentration.

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0.20

SF6 conc. (%)

0.15

0.10

Quick equilibration ▼ 0.05

Washout to 1/40 of starting concentration ▼

0.00 0

20

40

60

80

100 Time (s)

120

140

160

180

200

Figure 1.2–1 LCI manoeuvre.

1.3

LCI PARAMETERS

The LCI parameters measured by the Innocor are: Abbreviation FRC LCI

Name Functional Residual Capacity Lung Clearance Index

1.4

Unit L [BTPS]

CALCULATION OF FRC

Calculation of the Functional Residual Capacity is based on measured expired volume of SF6 during the multiple-breath washout. The FRC is calculated as:

FRC =

VSF 6 − VDS Cet (Start ) − Cet (N + 1)

where VSF6 = the cumulative net volume expired during the multi-breath washout – see below. N+1 = first breath where end tidal inert marker gas is below 1/40th of the starting concentration. (Cet(N+2) and Cet(N+3) must also be below 1/40th). VDS = equipment dead space. Cet(n) = End tidal concentration of breath n VSF6 is the cumulative net volume expired (i.e. the expired SF6 subtracted inspired SF6) during the multi-breath washout. The VSF6 is calculated as: VSF 6(BTPS ) =

 Flow

exp iration

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

BTPS ( t ) • FSF 6 ( t ) − FSF 6,exp, offset

• dt − C •  Flow ATP (t) • FSF6 (t) − FSF6,insp,offset • dt inspiration

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“expiration” integration is done from start of multi-breath washout to N+1, but only when flow is expiration. “inspiration” integration is done from start of multi-breath washout to N+1, but only when flow is inspiration. Flow = flow measured by flowmeter. FSF6 = SF6 measured by gas analyser corrected for flow-gas delay. FSF6,exp,offset = SF6 offset during expiration, measured prior to the test. FSF6,insp,offset = SF6 offset during inspiration, measured prior to the test. C = C1/C2 (conversion from ATP to BTPS). C1 = Conversion from ATP to STPD, see section 1.7. C2 = Conversion from BTPS to STPD, see section 1.7. 0.07 0.06

Integration interval

◄ Cet(start)

SF6 conc. (%)

0.05 0.04 0.03 0.02 0.01

Cet(N+1) ▼

0.00 50

70

90

110

130 Time (s)

150

170

190

Figure 1.4–1 Washout of an LCI manoeuvre. Example: VSF6 Cet(start) Cet(N+1) Vds(BTPS)

FRC =

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= = = =

0.210 l 0.05800% 0.00137% 0.127 l

0.210 − 0.127 = 3.58 (l,BTPS ) 0.05800 − 0.00137

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CALCULATION OF LCI

The LCI is calculated as: LCI =

VCE FRC

where VCE is the cumulative net volume expired during the multi-breath washout – see below. VCE is the cumulative net (i.e. corrected for equipment dead space) volume expired (i.e. the sum of tidal volumes) during the multi-breath washout. The VCE is calculated as: N

VCE =

 (VT (n) − VDS )) + Cet(N) n=1

Cet(N) Cet(Start) Cet(Start)

−

− 1

40

( VT (N + 1) − VDS )

Cet(N + 1) Cet(Start)

where n = breath after start of multi-breath washout. N = last breath where end tidal inert marker gas is above 1/40th of the starting concentration Cet(start). N+1 = first breath where end tidal inert marker gas is below 1/40th of the starting concentration. (Cet(N+2) and Cet(N+3) must also be below 1/40th). VT(n) = tidal volume of breath n. VDS = equipment dead space. Cet(n) = End tidal concentration of breath n Note: -

-

the last term in the equation is due to a linear interpolation between breath N and N+1. This is an improvement of the original calculation by ATS. Innocor s/w has by default turned this interpolation on, but can be disabled if wanted. Innocor s/w will by default subtract total equipment dead space when calculating V CE. Some users prefer to only subtract dead space between mouth and gas sample point. This is also supported. Turnover

Turnover

100

5

90

4.5

80

4 3.5

60

SF6-rel. (%)

SF6-rel. (%)

70

50 40 30

Cet(N) ▼

3

Cet(N+1) ▼

2.5 2 1.5

20

1

10

0.5

0 0

2

4 Vexp/FRC

6

8

0 7.2

7.4

7.6

7.8 Vexp/FRC

8

8.2

8.4

Figure 1.5–1 Turnover curve of an LCI manoeuvre.

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Innovision Example: FRC(BTPS) = 3.58 l VCE(BTPS) = 28.53 l

LCI =

28.53 = 7.97 3.58

1.6

LCI EVALUATION AND RESULTS

1.6.1

LCI manoeuvre acceptance

An LCI manoeuvre is correctly performed when: 1. The inert marker gas (SF6) is equilibrated with the lungs before the washout. 2. The end tidal concentration of the inert marker gas (SF6) is below 1/40th of the starting concentration over three subsequent breaths. Note on 1: The equilibration is measured as the deviation (x) between the inspiratory and expiratory concentration of the inert marker gas (SF6), and the limit is by default less than 2% relative at the end of the wash-in.

X=

Cin (n) − Cex (n)

(Cin (n) + Cex (n)) • ½

SF6 conc. (%)

0.065

Cin(n) ▼

0.060

▲ Cex(n)

0.055 40

42

44

46

48 Time (s)

50

52

54

Figure 1.6–1 Wash in of an LCI manoeuvre. Note on 2: • The end tidal concentration of the inert marker gas is below 1/40th of the starting concentration over three subsequent breaths. N is above the 1/40th, N+1, N+2 and N+3 is below.

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0.0030

N

1/40th

0.0025

N+1

N+2

N+3

SF6 conc. (%)

0.0020

0.0015

0.0010

0.0005

0.0000 150

155

160

165

170 Time (s)

175

180

185

190

Figure 1.6–2 Determination of stop of washout manoeuvre. 1.6.2

LCI test acceptance

Different criteria must be meet if an LCI test shall be accepted - in accordance to ERS/ATS standard: - Minimum 3 correctly performed manoeuvres - FRC must not differ more than 25% from median - LCI must not differ more than 10% or 1 TO in relation to median LCI (whichever is largest) The selection of best manoeuvres is in accordance to ERS/ATS standards: - Manoeuvre where FRC differs more than 25% from median FRC is excluded. - Manoeuvre where FRC differs more than 4.88% from mean FRC is excluded, if number of manoeuvres after exclusion is 3 or more. - Manoeuvre where LCI differs more than 10% or 1 TO in relation to median LCI (whichever is largest), is excluded, if number of manoeuvres after exclusion is 3 or more. If only two results exist, the median is the average of the two results. As default the Innocor s/w requires 3 manoeuvres, but can be changed to e.g. 2, which was the previous default. Note: ±4.88% from mean corresponds to 10% in relation to the lower. Note: the user can overwrite the selection of best manoeuvres.

1.6.3

LCI results

The results are summarised as: • The average FRC found in the accepted manoeuvres is recorded. • The average LCI found in the accepted manoeuvres is recorded.

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CONVERSION BETWEEN ATP, STPD AND BTPS

The volume of a number of moles (n) of gas molecules depends on the thermodynamic temperature (T) and the ambient pressure (P). The following relationship holds for dry gas: V = n·R·T/P where R = gas constant, and T is expressed in Kelvin (T(K) = 273.2 + t(ºC)). Air and expired gas are made up of gas molecules and water vapour. In a gas mixture saturated with water vapour and in contact with water (such as occurs in the lung) the number of water molecules in the gas phase varies with temperature and pressure. As the number of molecules is not constant, the above gas law should be applied to dry gas. This also holds outside the lung when gas saturated with water vapour is compressed or cools down. BTPS:

In respiratory physiology lung volumes and flows are standardised to barometric pressure at sea level, body temperature, saturated with water vapour: body temperature and pressure, saturated. Measured at ambient temperature, pressure, saturated with water vapour (e.g. expired gas, which has cooled down): ambient temperature and pressure, saturated. Like ATPS, but not saturated with water vapour (e.g. room air). Like ATPS, but dry (e.g. from a gas bottle). Oxygen consumption and carbon dioxide excretion are standardised to standard temperature (0 ºC), barometric pressure at sea level (101.3 kPa / 760 mmHg) and dry gas: standard temperature and pressure, dry.

ATPS: ATP: ATPD: STPD:

Correction from ATP to STPD. Multiply the ATP-value by:

273 C1 =  273 + t a

PB −

RH  PH2O ( t a ) 100 760

Correction from BTPS to STPD. Multiply the BTPS-value by: C2 =

P − 47 273  B 273 + 37 760

where ta PB RH PH2O(ta) Temperature [°C] 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14

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= = = =

ambient temperature in °C barometric pressure in mmHg relative humidity in % saturated water vapour pressure in mmHg at temperature ta, see table below

Water vapour pressure [mmHg] 4.7 5.2 5.6 6.1 6.5 7.0 7.4 7.9 8.3 8.8 9.2 9.8 10.5 11.2 12.0

Temperature [°C] 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29

Water vapour pressure [mmHg] 12.8 13.6 14.5 15.5 16.5 17.5 18.7 19.8 21.1 22.4 23.8 25.2 26.7 28.3 30.0

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Temperature [°C] 30 31 32 33 34 35 36 37 38 39 40

Water vapour pressure [mmHg] 31.8 33.7 35.7 37.7 39.9 42.2 44.6 47.1 49.7 52.4 55.3

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