Firenze 22/23.09.2016

FISIOPATOLOGIA E IMAGING FUNZIONALE DEL POLMONE

BPCO: diagnosi e valutazione di gravita’ Isa Cerveri

SC PNEUMOLOGIA

IRCCS

Fondazione Policlinico

San Matteo

Universita’di

Pavia

DIAGNOSIS AND SEVERITY CLASSIFICATION OF COPD

COPD as a complex disease with multiple pathological components ignored when spirometry is used as the only method to evaluate it

FEV1is a crude, not sensitive parameter

It correlates poorly with clinical parameters

Similar FEV1 may have different pathologies

Additional measures are needed to allow a more complete and clinically relevant assessment of the disease

Advances in quantitative CT scanning has emerged

as a noninvasive tool in the “phenotyping of COPD”,

with measures investigating changes in the aiways wall

and lumen and within the lung parenchyma

CT imaging quantitative assessments has shown

associations with parameters of airway physiology

Relationships of emphysema extent by HRCT to

lung elastic recoil and DLCO

Baldi et al., AJRCCM 2001

0

0,1

0,2

0,3

0,4

0,5

Sim

ple

reg

ress

ion

R 2

FEV1

FRC

RV

TLC

RV

/TLC

DL,C

O

DL,C

O/V

A

Chest 2004

Relationships of classical PFT variables to emphysema extent by

HRCT

Chest 2004

Predicting variables:

FRC

DL,CO/VA

FEV1/FVC post BD R2=0.71

Prediction of radiological emphysema

by pulmonary function data

Relationships between airway wall area by CT or OCT and

lung function in COPD

Coxson et al AJRCCM 2008

CT

OCT OCT

CT

Bronchodilator response in COPD In some patients, the FVC increases without an increase

in FEV1

Cerveri et al., JAP 2000

1 2 3 4

-1

0

1

2

3

4

Volume (L)

Flo

w (

L/s

)

FEV1 & FVC

responder

Cerveri et al., JAP 2000

1 2 3 4

-1

0

1

2

3

4

Volume (L)

Flo

w (

L/s

)

FVC responder

1 2 3 4

-1

0

1

2

3

4

Volume (L)

Flo

w (

L/s

)

FEV1 & FVC

responder

Bronchodilator response in COPD In some patients, the FVC increases without an increase in

FEV1

Bronchodilator response in COPD The increase in FEV1 is inversely related to the extent of

emphysema

FVC responders

FVC & FEV1 responders

Emphysema extent (%)

Δ F

EV

1 (

% p

red

icte

d)

0

12

24

20 30 40 50 60

Cerveri et al., JAP 2000

Cerveri et al. JAP 2000

Bronchodilator response in COPD Isolated volume responses are associated with a

paradoxical effect of lung volume on airway caliber

FVC & FEV1 responder FVC responder

131 patients firstly diagnosed with moderate COPD

(GOLD stage 2)

Three years follow-up study

Baseline wide multidimensional approach with comprehensive clinical, complete functional and imaging characterisation of the patients

0

10

20

30

40

Presence of emphysema

Frequent exacerbations prestudy

N. of patients

26,1% 24,4%

Baseline clinical characteristics

Cerveri I, COPD 2012

0

20

40

60

80

100

120

140

FRC RV FEV1post

%p

red

62±12

123±24 129±32

91±18

FVCpost

Baseline lung function

The mean FEV1 decline were 42±66 mL/y

0

20

40

60

80

100

Rapid decliners Non rapid decliners

FE

V1 d

eclin

e

(mL/y

)

88±76 mL/y

6±54 mL/y

Cerveri I, COPD 2012

MULTIVARIABLE ANALYSIS

The presence of emphysema at HRCT scan proved to be an

independent prognostic factor of rapid decline in FEV1

When the presence of emphysema was replaced by mean RV, the

model still remained significant

Odds ratios

(95% CI)

p Value

Model 1: <0.0001

● Smoking pack-years 1.02 (1.00, 1.03) 0.047

● Presence of emphysema 17.76 (4.21, 74.93) <0.001

● FEV1 3.64 (1.07, 12.38) 0.038

● Exacerbations per year requiring hospitalization during F/U 4.60 (1.53, 13.86) 0.001

Model 2: 0.002

● Smoking pack-years 1.01 (1.00, 1.02) 0.15

● Residual volume 1.84 (1.04, 3.24) 0.037

● FEV1 2.93 (1.16, 7.43) 0.023

● Exacerbations per year requiring hospitalization during F/U 2.58 (0.99, 6.72) 0.052

The rapid FEV1 decline may be identified by the presence of

emphysema, as assessed by HRCT scans or lung function

testing, in patients with a long smoking history

This supports the importance of lung volume

determination at the first assessment of COPD patients and,

only when needed, further imaging studies

CONCLUSIONS

Quantitative evaluation CT scan in COPD

%LAA-950 AWT-Pi10 (mm)

Vida Diagnostics, Coralville, Iowa,

http://www.vidadiagnostics.com/

Lung Functional Imaging in COPD

244 studies from 1967 to 2016

>200 studies from 2010 to 2016

FEV1 103%pred DLCO 119% pred

FEV165% pred DLCO 17% pred

FEV147% pred DLCO 63% pred

The routine clinical application of serial examinations limited because of the potential risks of cumulative exposure, even in older subjects with COPD

Need to perform CT imaging in patients at the lowest doses possible X ray–dose reduction strategies

Limited spatial resolution possible when low radiation doses are used (evaluation of wall thickeness in the small airways extremely difficult or impossible)

The reconstruction methods affect quantitative measurements and can alter comparability

Standardization of imaging protocols and methods

Availability of sophysticated techniques

Increased costs !!

Excellent safety and tolerability profile Major application of conventional MRI: pulmonary vessel emodynamics Technical problems due to the unique

caracteristics of lung tissue Recent refinements reducing the time

required for imagine acquisition

FEV1:52%; FEV1/FVC 40% FEV1:81%; FEV1/FVC 52%

FEV1:89%; DLCO 64% FEV1:28%; DLCO 32% FEV1:52%; DLCO:55%

A : He MRI

FEV1:46%; FEV1/FVC 53%

B : FDMRI

Patient with COPD and bullous emphysema

Evaluation of regional ventilation Depending on inhaled gas or injected

contrast agents Poor availability of polarized noble gases Expensive !!

Evaluation of regional ventilation and /or perfusion

Not depending on inhaled gas or injected contrast agents

Image registration and analysis complex Important advantages with good potential

for clinical translation

FEV189% pred DLCO 64% pred

FEV1 28% pred DLCO 32% pred

FEV1:52% pred DLCO:55% pred

CT For younger people, even with low dose adaptive iteraction methods, radiation

dose and long-term burden/risk remain a concern

For clinical application continued emphasys on dose reduction is essential

MRI MRI, without exposure to ionizing radiation, could provide an excellent alternative

for clinical application in COPD patients

Semplification of the acquisition and analysis of methods

Improvement of knowledge dissemination

CONCLUSIONS I

CONCLUSIONS II

PULMONARY FUNCTION TESTING

Widely accessible

Easy to implement

Straighforward measurements

They do not tell the whole story for patient populations and individual patient

IMAGING AND PULMONARY FUNCTION TESTING

COPD, as a complex and heterogeneous disease, can not be diagnosed

and treated with simple tools !!

A greater integration is necessary between imaging and pulmonary

function tests both in research, in clinical trials and in clinical practice !!

Reduced parenchymal density (LAA) and airway wall

thickening in asymptomatic smokers and COPD

Nakano et al, Chest 2002

Cerveri et al. JAP 2000

FVC & FEV1 responders

FVC responders

Bronchodilator response in COPD The increase in FEV1 is inversely related to functional

indices of emphysema