R. POLOSA - COI last 5 yrs

Lecture fees: Pfizer, GlaxoSmithKline, a number of european electronic cigarette industry and trade associations (including FIVAPE in France and FIESEL in Italy);

Research grants: Pfizer and GlaxoSmithKline;

Consultancy services: Pfizer, Global Health Alliance for treatment of tobacco dependence, ECITA, Health Diplomats;

Scientific advisor (pro bono): LIAF, IBVTA, CASAA

Chair: European Technical Committee for standardization on “Requirements and test methods for emissions of electronic cigarettes” (CEN/TC 437; WG4).

Impact of long term EC use on lung health

Prof. Riccardo Polosa

Institute of Internal Medicine

University of Catania

ITALY

PRODUCT TOBACCO

PRESENT

AEROSOL

FORMATION

MECHANISM

NUMBER OF

COMPOUNDS

IN AEROSOL

NUMBER

OF

TOXICANTS

TOXICANT FORMATION

MECHANISMS

UNTARGETED

EMISSIONS

CIGARETTE Yes Combustion &

pyrolysis of

tobacco

>7000 100–150 Transfer from tobacco

Pyrosynthesis of tobacco

Pyrolysis

Combustion

E-CIG No Vaporisation

of e-liquid 10–100 <5 Poorly quality e-liquids

(eg. contaminants)

Thermal degradation of

PG/VG (‘Dry wicking’)

Transfer of extractables &

leachables from device

during storage or heating

GCxGC-TOF-MS chromatograms

of cigarette smoke vs EC aerosol

E-cigarettes: reduced toxicants emission

Reduced exposure to toxicants in EC users M.L. Goniewicz et al. Nicotine Tob Res 2017

≈ 60% reduction ≈ 80% reduction

≈ 75% reduction ≈ 70% reduction

• EC use common and increasing

• Concern about the long-term health effects of vaping (in

vitro systems, animal studies, surveys)

• Very little is known about the health impact of long-term

vaping

The problems

• What is the long-term health impact of vaping (in real-life

situation)?

• Can we answer the question by prospective studies of well-

characterized EC users?

The questions

• large prospective studies of well-characterized EC users

(impractical, costly)

• extrapolating responses to EC in cell lines and/or in animal

models (does not directly apply to real-life situation)

• surveys (issues with working definitions, design, etc.)

Substantiating evidence for the long-term health impact of EC - 1

Risk Reduction

• detecting early changes of subclinical injury with highly sensitive functional tests (“healthy” smokers)

• documenting changes with more robust and validated investigational tools (EC users with pre-existing disease)

• population modelling (smoking related morbidity and mortality)

Risk Reductio

Risk Reduction

Substantiating evidence for the long-term health impact of EC - 2

Impact of long term EC use on lung function in “healthy” smokers switching to ECs

Campagna D, Cibella F, Russo C, et al. Clin Sci. 2016

Campagna D, Cibella F, Russo C, et al. Clin Sci. 2016

Impact of long term EC use on lung function in “healthy” smokers switching to ECs

Quitters Reducers Failures

0

5

10

15

20

pp

b

BL W-12 W-24 W-52

FeNO Between subject effects: p<0.0001

Impact of long term EC use on FeNO in “healthy” smokers switching to ECs

CHANGES IN BREATHOMICS: 1-YR RANDOMIZED SMOKING CESSATION TRIAL OF ECs

D. Campagna, et al. Eur J Clin Invest 2016

• NCT02396381

• NCT02649556

• NCT02103751

• NCT03020667

• ….

• Smoking abstinence by using ECs may improve respiratory function and symptoms

• No data about EC use in smokers with pre-existing disease

• We investigated changes in subjective and objective asthma outcomes in smoking asthmatics who switched to EC

1st F/up Visit

Assessment Timepoints

Baseline Pre-Baseline

Fo

rce

d E

xp

ira

tory

Vo

lum

e in 1

se

co

nd

(L

)

3.0

3.2

3.4

3.6

3.8

2nd F/up Visit

**

Impact of EC use on lung function in asthma

FEV1 improvement from baseline to 24 months

p=0.005 mean increase of 100mls

Harm

Reversal!

Regular EC use

3rd F/up Visit

Polosa et al. Discov Med 2016

FE

F2

5-7

5 (

L/s

ec)

2.4

2.6

2.8

3.0

3.2

3.4

1st F/up Visit

Assessment Timepoints

Baseline Pre-Baseline

2nd F/up Visit

**

***p=0.006

mean increase of 250mls/sec

p=0.001 mean increase of 360mls/sec

Harm

Reversal!

Regular EC use

3rd F/up Visit

Polosa et al. Discov Med 2016

Impact of EC use on lung function in asthma FEF25-75 improvement from baseline to 24 months

Pre-Baseline

Me

tha

cho

line

PC

20

(m

g/m

L)

1.0

1.5

2.0

2.5

3.0

3.5

Baseline 2nd F/up Visit

1st F/up Visit

Assessment Timepoints

**

p=0.003 mean increase of 1.2 DD

Harm

Reversal!

Regular EC use

3rd F/up Visit

Polosa et al. Discov Med 2016

Impact of EC use on lung function in asthma PC20 improvement from baseline to 24 months

AC

Q s

co

res

1.2

1.4

1.6

1.8

2.0

2.2

2.4

1st F/up Visit

Assessment Timepoints

Baseline Pre-Baseline

2nd F/up Visit

***

***p=0.001

mean decrease of 0.43

p=0.001 mean decrease of 0.56

Harm

Reversal!

Regular EC use

3rd F/up Visit

Polosa et al. Discov Med 2016

Impact of EC use on lung QoL in asthma ACQ improvement from baseline to 24 months

• Smoking abstinence by using ECs may improve respiratory function and symptoms

• No data about EC use in smokers with COPD

• We investigated changes in subjective and objective respiratory outcomes in COPD smokers who switched to EC

Time

Baseline 12 Months 24 Months 36 Months

Post

-Bro

nch

odila

tor

FE

V1 (

L)

0.6

0.8

1.0

1.2

1.4

1.6

1.8

2.0

COPD EC Users

COPD Controls

p = 0.233

Polosa R et al. Respir Res 2017

No change in post B/Dil FVC No change in %FEV1/FVC

Impact of EC use on lung function in COPD No change from baseline to 36 months

Time

Baseline 12 Months 24 Months 36 Months

CO

PD

Exa

cerb

atio

ns/y

ear

0

1

2

3

4

COPD EC Users

COPD Controls

p = 0.004

Polosa R et al. Respir Res 2017

Less respiratory exacerbations

Impact of EC use on clinical outcomes in COPD Improvement from baseline to 36 months

Time

Baseline 12 Months 24 Months 36 Months

CO

PD

Ass

ess

ment

Tool (

CA

T)

Sco

res

10

15

20

25

30

COPD EC Users

COPD Controls

p=0.019

Polosa R et al. Respir Res 2017

Improved CAT score

Impact of EC use on QoL in COPD Improvement from baseline to 36 months

Time

Baseline 12 Months 24 Months 36 Months

6-M

inu

te W

alk

Dis

tan

ce (

me

tre

s)

200

300

400

COPD EC Users

COPD Controls

p = 0.001

Polosa R et al. Respir Res 2017

Improved 6MWD

Impact of EC use on physical performance in COPD Improvement from baseline to 36 months

• The large majority of EC users are smokers or ex-smokers

• Smoking hx and previous smoking hx are key confounders

• Changes in health outcomes take time (early sensitive

indicators – e.g. HRCT, FEF25-75)

The challenges

STUDY OBJECTIVE:

Detecting early changes of subclinical lung damage in a prospective study of well-

characterized EC users who have never smoked in their life

Results – Spirometry

Results – eCO and eNO

Results – Lung HRCT

Scans showed no pathological findings. In particular no CT

features compatible with early signs of :

• COPD (i.e. parenchymal micronodules, ground-glass

opacity, or macroscopic emphysema)

• Lipoid pneumonia

• Popcorn lung disease

Of note, no early pathological signs were observed in subjects with the highest e-liquid consumption (i.e. 5

mls/day) and longest overall vaping hx

(i.e. 57 months)

Impact of long term EC use on lung health Take Home Message

ECs are unlikely to raise significant health concerns for the respiratory tract under normal condition of use

Former smokers using and smokers intending to use ECs should receive correct information about residual risks and potential benefits

Promoting further access to ECs may reduce risk and reverse harm

Fabio Cibella National Research Council of Italy, Institute of Biomedicine and Molecular Immunology, Palermo, Italy Donald W. Cockroft Department of Medicine, Division of Respirology, Royal University of Saskatchewan, Canada Donald P. Tashkin David Geffen School of Medicine, UCLA, Los Angeles, California, USA Mario Malerba Department of Internal Medicine, University of Brescia and AOU Spedali Civili, Brescia, Italy Umberto Prosperini Ospedale “San Vincenzo” - ASP Messina, Taormina (ME), Italy. Cristina Russo Giovanni Ciampi MCAU ARNAS Garibaldi, Catania, Italy. Jaymin B. Morjaria Department of Respiratory Medicine, Royal Brompton & Harefield Hospital Foundation Trust, UK

Pasquale Caponnetto Marilena Maglia

Valeria Vinci Centro Prevenzione e Cura Tabagismo, University of Catania

Riccardo Polosa Cosimo M. Bruno Massimo Caruso Alfredo Fisichella Davide Campagna Maria Domenica Amaradio Dipartimento di Medicina Clinica e Sperimentale, University of Catania

Acknoweldgements