Health Surveillance of asbestos-exposed workers at Helsinki Asbestos 2014

Health surveillance of asbestos-exposed workers

Prof. Massimo Corradi, MD

University Hospital of Parma, Italy

[email protected]

No conflict of interest

Clin Respir J 2014; 8: 1–10

Asbestsosis

Pleural plaques

Benign asbestos pleural effusion

Rounded atelectasis

Diffuse pleural thickening

Mesothelioma

Lung cancer

NIOSH 2007

Asbestosis deaths in USA

Time trend in age-adjusted mesothelioma worldwide

Delgermaa. Bull World Health Organ 2011;89:716–724C

Peak incidence of mesothelioma

Int. Agency Res. Cancer (IARC). 2007.

Asbestos-exposed workers have justifiable anxiety about their future and

seek reassurance from the medical profession

These people consult physicians for many reasons: • to be screened for asbestos-related disease• for evaluation of specific symptoms• for treatment and advice• for evaluation of impairment

Clin Respir J 2014; 8: 1–10

Asbestsosis

Asbestosis is commonly associated with prolonged exposure, usually over 10 to 20 years.

However, short, intense exposures to asbestos, lasting from several months to 1 year or more, can

be sufficient to cause asbestosis.

The chest radiograph (ILO-BIT, B-reader) remains an useful tool for the radiographic diagnosis of asbestosis

HRCT has an important role when experienced readers disagree about the presence or absence of abnormalities on a high quality chest film

Health surveillance for asbestosis

There is no effective treatment for asbestosis but this is an independent risk factor for bronchial carcinoma and it is evidence of heavy asbestos exposure

Stopping smoking in subjects suffering from asbestosis will reduce the incidence of bronchial carcinoma

Markowitz. AJRCCM Vol. 188, No. 1 (2013), pp. 90-96.

Clin Respir J 2014; 8: 1–10

Asbestsosis

Pleural plaques

Benign asbestos pleural effusion

Rounded atelectasis

Diffuse pleural thickening

Health surveillance for asbestos-related benign pleural diseases

There is no effective treatment for asbestos-related benign pleural diseases but these are markers of exposure

The presence of pleural plaques has not been shown to be an aetiological factor for thoracic cancers

Ameille. Rev Mal Respir. 2011

The threshold limit 80 % for FEV1 74 % for DLCO

`Vehmas et al. Int Arch Occup Environ Health (2013)

Health surveillance of benign asbestos related diseases

Imaging techniques (RX/CT) are mandatory for diagnostic purposes

Lung function test (spirometry and DLCO) are necessary to grade the disease and to define the prognosis (thus useful in the follow up)

Clin Respir J 2014; 8: 1–10

Asbestsosis

Pleural plaques

Benign asbetos pleural effusion

Rounded atelectasis

Diffuse pleural thickening

Mesothelioma

Medical and public health benefits of screening for mesothelioma have not been demonstrated

To date, there are no scientific data that quantitate the contribution of imaging to the early

detection of mesothelioma

Early detection will result in early treatment (however prognosis seems to be more closely linked to cell type than timing of treatment)

Blood/pleural biomarkers for mesothelioma

Mesothelin

Osteopontin

YKL-40

Fibulin

Megakaryocyte potentiating factor

CA125

High-mobility group box 1 (HMGB1)

Vascular endothelial growth factor

Circulating tumor cells

“omic”approach

Endothelial cell

miR625-3P

Thioredoxin 1

miR126

Procalcitonin

Pubmed search 2014-2012

Clin Respir J 2014; 8: 1–10

Asbestsosis

Pleural plaques

Benign asbetos pleural effusion

Rounded atelectasis

Diffuse pleural thickening

Mesothelioma

Lung cancer

Lung Cancer (C33-C34): 2003-2006One-Year Relative Survival (%) by Stage, Adults 15-99, Former Anglia Cancer Network

1950-1990Randomised and non randomised controlled trials:

John Hopkins Lung ProjectMemorial Sloan Kettering Lung ProjectMayo Lung ProjectCzechoslovakian StudyNorth London Cancer StudyErfurt County StudyKaiser Permanente Study

Chest radiograph ± sputum cytology every 4 to 12 months compared to less frequent or no screening over 3 to 16 years

52000 subjects in intervention groups and 48000 in control groups

1950-1990

Intervention groups:More lung cancersMore early stage lung cancersMore resectable lung cancers

No reduction in lung cancer mortality

Lung Cancer Screening Tools

Sputum Cytology

Chest X-ray

Bach. ACCP guidelines, Chest 2007

Computed Tomography Screeningand Lung Cancer Outcomes

Increase of• cases• operated cases

Back. JAMA 2007

No change in • late

diagnosis• mortality

CT Screening for Lung Cancer Spiraling Into Confusion?

Black, WC, and Baron, JA

Editorial

Formulation of screening policy should await the rigorous assessment provided by ongoing randomized controlled trials (National Lung Screening Trial and NELSON Trial).

JAMA 2007

NLST: Design

time0 1 2 3 4 5 6 7 8

N 53,476 • Age 55-74 ys• Smoking hist.

≥30 PY

CT Arm

CXR Arm

Randomize

F/U

T0

T1

T2 Aberle. N Engl J Med 2011

Non-calcified nodules ≥4 mm in CT or any size in X-ray were referred for diagnostic work-up

Primary outcome: lung cancer related mortality

National lung screening trial (NLST)

Aberle. N Engl J Med 2011

320 participants were needed to screen to prevent 1 lung cancer death

….and CT Scan in asbestos exposed workers…..?

Ollier. Chest 2014

A meta-analysis of cohort studies involving CT scan in former asbestos-exposed workers

Ollier. Chest 2014

The prevalence compared favourably with the reported prevalence in the larger available trials in

heavy smokers (1%; CI 95%: 0.09% - 1.1%)Ollier. Chest 2014

European Screening Trials Overview

NELSON DLCST ITALUNG LUSI DANTE MILD

Nr rounds 4 5 4 5 5 10 or 5

Enrollement 15,464 4,104 3,206 3,551 2,472 3,581

Completed Y Y Y N Y N

Baseline detection 0.9% 0.8% 1.5% 1.0% 2.2% 0.8%

Incidence 0.5% 0.6% 0.4% - 0.5% 0.5%

de Koning, ECCO-ESMO meeting, Sept. 2011

Lung cancer in asbestos-exposed workers occurred at least 20-25 years following the initial exposure. Thus, such screening should

not start prior to the prolonged latency period

From: Benefits and Harms of CT Screening for Lung Cancer:  A Systematic Review

JAMA. 2012;307(22):2418-2429.

Journal of Surgical Oncology 2014

Journal of Surgical Oncology 2014

Potential harms with CT scan

Post-occupational follow-up may involve risks to health, particularly repeated irradiation and invasive diagnostic procedures

It is also necessary to consider the psychological consequences inherent in all screening programmes

Nodule(s) (%) Cancer (%)

ELCAP 23 2.7

Shinshu Univ 5.1 0.4

Hitachi HCC 26.3 0.44

ALCA 11.5 0.8

Mayo 51 2.0

Univ of Munster 43 1.5

Univ of Milano 19 1.1

Univ de Navarra 31.9 1.32

Beaumont, Ire 20.7 0.23

SMC, Korea 35 0.17

Helsinki Univ. 18.4 0.8

LSS, NCI 20.5 1.9

City Univ, NY 32 0.7

IELCAP 13 1.3

NY-ELCAP 41.8 1.6

Can-ELCAP 76 2.0

Depiscan, France 45.2 2.4

Cosmos, Italy 43 1.7

Pittsburgh 40.6 1.5

DANTE, Italy 15 2.2

Number of pulmonary nodules

CT scans(UH Parma)

•5000/year•100%

Solitary Nodules•500/year*•10% of CT scans

Stage I lung cancer•25/year•0.5% of CT scans •5% of nodules

PET FOR ALL?

Biomarkers to be developed?

Lung function tests

Biomarkers

CT screening inhigher individual risk

mRNA

One miRNA

mRNA

mRNA

mRNA

mRNA

…

small noncoding RNAs that regulate gene expression by binding complementary sequences of target mRNAs and inducing their degradation or translational repression

One miRNA has multiple targets

microRNA: a new class of biomarkers

PNAS, 2011

ConclusionsPost-occupational follow-up might reduce the

mortality of lung cancer due to asbestos

Lung fuction and biomarker driven screening procedures may reduce the very hight rate of false positives observed with CT scan

The theoretical benefits, have to be seen in perspective with the risks to physical and psychological health related to diagnostic procedures

SMOKING CESSATION is still a priority!

Thanks to

Antonio MuttiMatteo GoldoniMarcello TiseoNicola Sverzellati

Università degli Studi di Parma