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Presented by Professor Massimo Corradi from University of Parma, Italy.
Citation preview
Health surveillance of asbestos-exposed workers
Prof. Massimo Corradi, MD
University Hospital of Parma, Italy
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