Presented by Professor Massimo Corradi from University of Parma, Italy.

1. Health surveillance of asbestos-
exposed workers
Prof. Massimo Corradi, MD
University Hospital of Parma, Italy
massimo.corradi@unipr.it

2. No conflict of interest

3. Clin Respir J 2014; 8: 1–10
 Asbestsosis
 Pleural plaques
 Benign asbestos pleural effusion
 Rounded atelectasis
 Diffuse pleural thickening
 Mesothelioma
 Lung cancer

4. NIOSH 2007
Asbestosis deaths in USA

5. Time trend in age-adjusted
mesothelioma worldwide
Delgermaa. Bull World Health Organ 2011;89:716–724C

6. Peak incidence of mesothelioma
Int. Agency Res. Cancer (IARC). 2007.

7. 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

8. 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.

9.  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

10. 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.

11. Clin Respir J 2014; 8: 1–10
Asbestsosis
 Pleural plaques
 Benign asbestos pleural effusion
 Rounded atelectasis
 Diffuse pleural thickening

12. 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

13. The threshold limit
80 % for FEV1 74 % for DLCO
`Vehmas et al. Int Arch Occup Environ Health (2013)

14. 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)

15. Clin Respir J 2014; 8: 1–10
 Asbestsosis
 Pleural plaques
 Benign asbetos pleural effusion
 Rounded atelectasis
 Diffuse pleural thickening
 Mesothelioma

16. 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)

17. 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

20. Clin Respir J 2014; 8: 1–10
 Asbestsosis
 Pleural plaques
 Benign asbetos pleural effusion
 Rounded atelectasis
 Diffuse pleural thickening
 Mesothelioma
 Lung cancer

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

23. 1950-1990
 Randomised and non randomised controlled trials:
 John Hopkins Lung Project
 Memorial Sloan Kettering Lung Project
 Mayo Lung Project
 Czechoslovakian Study
 North London Cancer Study
 Erfurt County Study
 Kaiser 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

24. 1950-1990
 Intervention groups:
 More lung cancers
 More early stage lung cancers
 More resectable lung cancers
 No reduction in lung cancer mortality

25. Lung Cancer Screening Tools
 Sputum Cytology
 Chest X-ray
Bach. ACCP guidelines, Chest 2007

27. Computed Tomography Screening
and Lung Cancer Outcomes
Increase of
• cases
• operated cases
Back. JAMA 2007
No change in
• late diagnosis
• mortality

28. 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

29. NLST: Design
time
0 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

30. National lung screening trial (NLST)
Aberle. N Engl J Med 2011
320 participants were needed to screen
to prevent 1 lung cancer death

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

35. Ollier. Chest 2014
A meta-analysis of cohort studies involving CT
scan in former asbestos-exposed workers

36. Ollier. Chest 2014

37. 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

38. 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

39. 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

40. From: Benefits and Harms of CT Screening for Lung Cancer: A Systematic Review
JAMA. 2012;307(22):2418-2429.

41. Journal of Surgical Oncology 2014

42. Journal of Surgical Oncology 2014

43. 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

44. 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

45. 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?

46.  Lung function tests
 Biomarkers
CT screening in
higher individual risk

48. 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

49. PNAS, 2011

50. Conclusions
 Post-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!

51. Thanks to
 Antonio Mutti
 Matteo Goldoni
 Marcello Tiseo
 Nicola Sverzellati
Università degli Studi di Parma