Occupational Lung

Diseases
Part II
 Case #1
45 yo sandblaster develops SOB, diffuse
miliary infiltrates and calcified
hilar nodes. Which of the following
is correct?
a) Lung damage due to asbestos exposure
b) Increased likelihood of tuberculosis
c) Disease will abate if exposure ends
d) Obstructive pattern likely on PFTs
e) ACE levels will be high
 Silicosis
General
• Most prevalent occupational Dz in
the world
• Years of Exposure - Crystalline
silica
• 20 to 30 year latency
• Progression despite stopping
exposure
• Mining, glassmaking, ceramics,
brickyards, foundries, SAND BLASTING
 Silicosis
Clinical
• Simple Characteristics
Nodular
– Small nodules, UPPER Lobes other
• Complicated Nodular (AKA PMF)
– Big nodules (> 1 cm), coalesce, retract up,
traction bronchiectasis
– Fibrosis, dystrophic calcification (similar to TB)
– May progress to respiratory failure/death
• Silico-proteinosis
– Overwhelming exposure (~5 year lag)
– May be rapidly fatal
• Hilar LAD with “Eggshell” calcification
• Nodules may cavitate - Think TB!
Normal
Silicosis
Silicosis
Black silicotic nodules & pleural fibrosis
Silicotic Nodule
Complicated Silicosis AKA PMF
End stage silicosis
Silico-proteinosis
Eggshell Calcification
 Silicosis
Associations &
Complications
• Mycobacterial Disease (MTB and
Mycobacterial Disease (MTB and
MOTT)
– Macrophage Dysfunction
– Any acute clinical or CXR change
should prompt investigation
• Slight increase risk of lung Cancer
• Broncholithiasis
• Does NOT cause Asthma
Multiple cavities in silicosis
 Silicosis
Diagnosis and
Treatment
• Exposure Hx + Typical Radiographic signs
• If Dx in doubt (i.e. atypical
presentation)
– FOB + TBBx
• Stop ongoing exposure
• Anti-inflammatory/cytotoxic drugs
currently of no proven benefit
• Silico-proteinosis: Whole lung lavage +/-
steroids
• Early Dx and RX of MTB and MOTT
• Yearly PPD - Rx if +
 Case #1
45 yo sandblaster develops SOB, diffuse
miliary infiltrates and Ca++ hilar
nodes. Which of the following is
correct?
a) Lung damage due to asbestos exposure
b) Increased likelihood of tuberculosis
c) Disease will abate if exposure ends
d) Obstructive pattern likely on PFTs
e) ACE levels will be high
 Case #2
65 yo retired insulation worker with 3
yr Hx of gradually increasing DOE.
Coupled with a reliable exposure Hx,
which of the following is NECESSARY to
make the Dx?
• Restrictive/obstructive PFTs
• Bilateral fixed basilar crackles
• Ferruginous bodies in BAL
• Radiographic evidence of lung fibrosis
• Mineralogical confirmation by lung Bx
 Asbestos
Related Diseases
• Pulmonary Asbestosis
• Asbestos-related Pleural Plaques
• Benign Asbestos Pleural Effusion
• Diffuse Pleural Fibrosis
• Rounded Atelectasis
• Mesothelioma
• Lung cancer
• Gastrointestinal Cancer
 Asbestos
Common Occupations at
• Pre WW II
Risk
– ship building, repair, or refitting
industries

• Post-World War II: construction and

transport industries.
– Insulators and laggers, Carpenters,
Plumbers, Electricians
– Welders, boiler makers, scrap metal workers
– Brake pads
– Maintenance, demolition, removal
 Asbestos
Pathogenesis
• DEPOSITION
– Short fibers deposit at bifurcations
– Longer Fibers ( >3um) penetrate into the lung parenchyma
• PHAGOCYTOSIS & TRANSPORT
– Shorter fibers: transported to interstitium and pleural
space
– Longer fibers : ferruginous body
• INFLAMMATION & FIBROSIS:
– Activated Macrophages: inflammation and fibrosis
• CARCINOGENESIS:
– Altered apoptosis, ROS, adsorption/ concentration of
toxins
 Pulmonary Asbestosis
• Pulmonary parenchymal fibrosis
• Associated with moderate exposure >10yr
• Latency >30yr
• Clinical Symptoms and Signs:
– Dyspnea – early and progressive
– Cough – NP, persistent and paroxysmal
– Chest pain and tightness
– Mid to late inspiratory Basilar crackles (32-64%)
– Clubbing (32-34%)
– Right Heart Failure/ Cor Pulmonale
 Pulmonary Asbestosis
• CXR
• 15-20 % may have a normal CXR in the
face of Histological diagnosis
• Typical Findings
– small, irregular opacities, primarily in
bases (early)
– coarse interstitial markings
– basal fibrosis changes (irregular/
reticular)
– shaggy heart border
 Pulmonary Asbestosis
• High Resolution CT
• Parenchymal abnormalities in 96% of
patients
– dense parenchymal bands
– thickened interlobular septa
– pleural-based and sub pleural
irregularities
– peripheral interstitial lines or
reticulation
– honeycombing
 Asbestosis has a pattern of UIP with
peripheral honeycombing and asbestos bodies.
 Pulmonary Asbestosis
PULMONARY FUNCTION TESTS
• Restrictive ventilatory defect is
typical
• Reduced diffusing capacity
• 50% showed a mixed or obstructive
function profile
 Pulmonary Asbestosis
Diagnosis
History of exposure and radiographic evidence
(CXR or HRCT) are essential and the others
confirmatory

• Reliable exposure history

• CXR or HRCT evidence of fibrosis
• Appropriate lag time
• Restrictive ventilatory pattern
• Crackles
• Clubbing
• ** Mineralogical Assessment of Lung Tissue ( >
0.5 ferruginous body/ cm2 –equivalent to 1000-
7000 uncoated fibers or > I million fibers /
gm dried lung) suggest significant exposure
 Asbestos
Pleural Plaques
• Parietal pleura
• Lateral and posterior mid-zones and
diaphragm
• Frequently calcified
• SPARE the apices and costophrenic sulci
• Sole manifestation of asbestos exposure
in 50%
• Usually asymptomatic
• Marker of significant exposure
• Large Plaques (> 4 cm): increased risk
for Mesothelioma
 Asbestos
Benign Asbestos
Pleural Effusion
• Earliest manifestation of
significant exposure
• Latency 10-20 yrs
• Small, unilateral, and asymptomatic
• Exudative, macrophage predominance
• Atypical cytology: hard to R/O
mesothelioma
• Usually resolves with some residual
pleural fibrosis
 Diffuse Pleural
Fibrosis
• Diffuse pleural
thickening
• Visceral pleura
• Usually INCLUDES
costophrenic angles
• Restrictive
ventilatory defect
• Significant symptoms
and disability
• Can occur in absence
of parenchymal Dz
• Latency >20 yrs
 Rounded Atelectasis
• Trapping of lung
adjacent to a pleural
plaque
• Pleural in-folding
• Pseudo-tumor
appearance
• Has a wedge or
lenticular shape
• Characteristic “comet
tail”
• Contiguous with
pleural thickening
 Mesothelioma
• Asbestos is the only known risk factor (8-
13% lifetime)
• 11- 16% of cases: no known exposure
• Indirect exposure may be a significant
risk
• Latency: 30-40 years;
• Clinical Symptoms and Signs:
– Dyspnea and CHEST PAIN (Rarely, asymptomatic )
– Unilateral dullness, palpable chest wall
masses, and ipsilateral scoliosis
 Mesothelioma
CHEST X-RAY
• Large, unilateral pleural effusion (60% on Right)
• Pleural mass or diffuse thickening (‘lumpy
bumpy”)
• MOST will have pleural plaques and/or
calcifications
• 20% have radiographic signs of ASBESTOSIS
• Ipsilateral mediastinal shift can be seen
secondary to encasement of lung by a thick rind
of tumor.
 Mesothelioma
DIAGNOSIS: Often misdiagnosed initially
• Thoracentesis alone (26%) or closed pleural
biopsy (39%) often suggestive but don’t
provide enough diagnostic material to
confirm Dx.
• Pleural Fluid Hyaluronidase is usually
elevated (not Dxic)
• Negative results do not exclude Dx
• VATS or open thoracotomy: up to 98% Dx yield
• 10% seed the biopsy site
 Mesothelioma
Clinical Course
• Progressive SOB and chest pain
• Hypoxia due to SHUNT ( refractory to O2 )
• Local invasion: Dysphagia, Hoarseness, Cord
compression, Brachial plexopathy, Horner's
syndrome, SVC syndrome
• Paraneoplastic syndromes – DIC, Trousseau’s
Syndrome, Thrombocytosis, Coombs-positive
hemolytic anemia, Hypoglycemia, Hypercalcemia from
PTH - like peptide
• Median survival : 6 - 18 months
 Asbestos
Lung Cancer
• Asbestos alone increases lung cancer risk
6-fold
• Smoking alone Increases lung cancer risk
11-fold
• Asbestos + Smoking SYNERGISTICALLY
increases lung cancer risk 59-fold!!
• Most commonly lower lobe, peripheral,
multi-centric, ADENOCARCINOMA
 Asbestos-associated
Disease
Management
• Largely Supportive
• Remove exposure
• Cancer surveillance
• O2 as needed
• Prepare for court!
 Case #2
65 yo retired insulation worker with 3
yr Hx of gradually increasing DOE.
Coupled with a reliable exposure Hx,
which of the following is NECESSARY
to make the Dx?
• Restrictive/obstructive PFTs
• Bilateral fixed basilar crackles
• Ferruginous bodies in BAL
• Radiographic evidence of fibrosis
• Mineralogical confirmation by lung Bx
 Case #3
62 yo former nuclear reactor worker
presents with insidious onset DOE, dry
cough, weight loss and arthralgias.
Which of the following in NOT true?
a) Pathology identical to sarcoidosis
b) Involves Delayed-type hypersensitivity
c) Steroids are of NO benefit
d) Lymphocyte proliferation test confirms
Dx
 Berylliosis
• First associated with Dz in
fluorescent light workers
• Current occupations at risk:
Aerospace, electronics,
ceramics, telecommunications,
metal workers, nuclear
weapons/reactors
• Indirect exposure important
 Berylliosis
• Acute Beryllium Disease (RARE)
– Acute toxic chemical pneumonitis,
– Brief exposure to extremely high levels of
airborne beryllium
• Chronic Beryllium Disease (~5% exposed)
– Chronic granulomatous pulmonary disease
– Beryllium-specific, cell-mediated immune
response
– Multi-system disorder, indistinguishable
from Sarcoid
 Berylliosis
• Delayed-type hypersensitivity Rxn
• Enters body via lungs
• Acts as an antigen or hapten
• Activates CD4+ lymphocytes (via IL-2
receptor)
• Chemokines/granuloma formation
• Carcinogenic
• HLA-DPb1(Glu 69) was found in 97% of
patients with CBD and only in 30% of
controls
 Berylliosis
Acute
• Cough
• Chest pain
• Blood-tinged sputum
• Crackles
• Air-space disease on CXR
 Berylliosis
Chronic
• Clinical: Similar to Sarcoidosis
– Pulm: Dyspnea, Cough, Chest pain
– Systemic: Weight loss, Fatigue, Arthralgias
– PE: Crackles
• CXR: ill-defined fibro-nodular opacities UL>LL
– Hilar LAD 40%
– Fibrosis, volume loss, honeycombing late
• PFTs: Restriction, Obstruction or Both and
reduced DLCO
• Labs: hyperuricemia, hypercalcemia/calciuria
elevated ACE
HRCT can be negative in ~25% patients with +BeLPT
 Berylliosis
Diagnosis
1. Exposure Hx
2. Clinically compatible lung disease
3. Radiological fibro-nodular Dz
4. Impaired Lung Fxn
5. Granuloma in lung or lymph nodes
6. + BeLPT (BAL more sensitive than
blood) clonal proliferation of
sensitized subsets of CD4 lymphocytes using
tritiated thymidine uptake
4 of 6 makes Dx as long as one is +BeLPT
 Berylliosis
Treatment
Acute
– Self-limited, remove exposure,
monitor

Chronic
– Steroids: long term treatment
improves outcome but not curative
– Relapse with withdrawal of Rx:
stays in lungs forever
 Case #3
62 yo former nuclear reactor worker
presents with insidious onset DOE,
dry cough, weight loss and
arthralgias. Which of the following
in NOT true?
a) Pathology identical to sarcoidosis
b) Involves Delayed-type
hypersensitivity
c) Steroids are of NO benefit
d) Lymphocyte proliferation test
confirms Dx
 Case #4
47 yo cotton mill worker with no PMH
presents with a hx of recurrent shortness
of breath and chest tightness most
prominent on the first day of the work
week. Which of the following is FALSE?
a) Associated with refined cotton fibers
b) Sx represent acute bronchoconstriction
c) Chronology of Sx severity represents
tachyphylaxis
d) Ongoing exposure may produce irreversible
impairment
 Byssinosis
General
Characteristics
Inhalation of ORGANIC DUST
• Cotton
• Hemp
• Flax
• Sisal
NOT immune mediated/ no sensitization needed
TWO patterns of pulmonary Response
• Acute bronchospasm: “Monday Morning”
chest tightness
• Chronic Bronchitis
 Byssinosis
Etiology
• Exposure to CRUDE fibers
• Etiology debatable
– Dust Vs endotoxin
– Mast cells seem to be involved,
NOT histamine
– Inflammation
• Some correlation between Acute
Sx and chronic decline in FEV1
 Byssinosis
Diagnosis & Treatment
• Appropriate exposure Hx
Cotton opener/carder >> winder/spinner
• Sx most prominent first shift of work
week
– 5% or 200cc cross-shift decline FEV1
• PE and CXR usually normal
• Chronic Bronchitis
– Airflow obstruction with air trapping
– Severely reduced DLCO suggest other Dx
• Avoidance
• Cromolyn sodium
 Case #4
47 yo cotton mill worker with no PMH
presents with a hx of recurrent shortness
of breath and chest tightness most
prominent on the first day of the work
week. Which of the following is FALSE?
a) Associated with refined cotton fibers
b) Sx represent acute bronchoconstriction
c) Chronology of Sx severity represents
tachyphylaxis
d) Ongoing exposure may produce irreversible
impairment
 Case #5
57 yo coal miner c/o progressive
dyspnea and black sputum. Which
of the following is INCORRECT?
a) Primarily lower lobe abnormality
b) Asthenic habitus and older age
increase risk
c) No increased risk of TB
d) No progression if exposure stops
 Coal Workers
Pneumoconiosis
• Inhalation of coal dust
• Radiographic Dx
• 3 Clinical Types
1. Simple CWP
2. Complicated CWP (AKA PMF)
3. Caplan’s Syndrome
 Coal Workers
Pneumoconiosis
Pathogenesis
Inhaled Dust

Phagocytosis

Macrophage Activation
CWP Emphysema
Reactive Oxygen Species

Inflammatio Proteas
n es
Fibrinogene
 Coal Workers
Pneumoconiosis
Simple CWP
• Small rounded opacities on CXR
(“coal nodules”)
• Upper lung zones (mid and
lower later)
• Minimal if any PFT impairment
• Predisposes to Complicated CWP
Simple CWP
 Complicated CWP
Progressive Massive
Fibrosis
• Nodules >1 cm
• Coalescence of “simple” nodules
• Associated fibrosis and volume loss
• Upper/mid lung zones (hila retracted up)
• Dust + Host Factors
• Risk Factors: Asthenic habitus, older
age, length of exposure, Higher ILO
category simple CWP
• No progression after they stop mining
• Dyspnea, severe progressive ventilatory
impairment, melanoptysis
Complicated CWP
 Caplan’s Syndrome
• Coal Workers with Rheumatoid
arthritis
• Develop ‘crops’ of macrobiotic
nodules on background of simple CWP
• Peripheral/sub-pleural distribution
• Frequently cavitate
• Associated with increased RF,
cigarette smoking and rheumatoid
nodules elsewhere
Caplan’s
Syndrome
 Case #5
57 yo coal miner c/o progressive
dyspnea and black sputum. Which
of the following is INCORRECT?
a) Primarily lower lobe abnormality
b) Asthenic habitus and older age
increase risk
c) No increased risk of TB
d) No progression if exposure stops
 Occupational Lung
Disease
• Exposure Hx
Summary
• Know typical jobs at risk
• Know typical radiographic
presentations
• Know Associated illnesses
• Know unique diagnostic
characteristics
• Also be familiar with occupational
asthma and RADS
The End
 Case #1
• 21 yo student, no PMH, lab technician
• Recurrent SOB, cough, fever, chills,
and malaise lasting several days
• Increased ESR
• Ill defined diffuse patchy infiltrates
• Reduced lung volumes and DLCO
• Sx begin on days he does rat
experiments
 Case #1
What is the best treatment for this
condition?
• Inhaled Cromolyn Sodium
• Prednisone
• Inhaled corticosteroids
• Discontinue visits to the animal
facility
• No Treatment
Hypersensitivity Pneumonitis
 Hypersensitivity
Pneumonitis
• Immunologic-induced, non-IgE
mediated inflammatory lung disease
• Sensitization and subsequent re-
exposure to organic dusts
• Terminal bronchioles, interstitium
and alveoli (NOT large airways)
• Mononuclear cell infiltrate with
frequent granuloma formation
 Hypersensitivity
Pneumonitis
1.
Inciting
Microbial Agents
Agents
• Bacteria
• Fungi
• Amoebae
2. Animal Proteins
• Avian
• Mammal
• Insect
• other
3. Low Molecular Weight Chemicals
• Isocyanates, etc
 Hypersensitivity
Pneumonitis
Host Factors
• No HLA association
• Not IgE mediated
• More common in NON-smokers
• Age: infrequent in kids
• Sx increased with pregancy
 Hypersensitivity
Pneumonitis
Histopathology
• Distinctive but NOT
Pathognomonic
• Triad i. Cellular bronchiolitis
ii. Interstitial mononuclear
infiltrate
iii. Small, loosely formed,
non- necrotizing granuloma
• Chronic: Fibrosis, Honeycombing
 Hypersensitivity
Pneumonitis
Clinical Presentation
• History: Important for Dx and Exposure
intervention
• Acute: Brief, intense exposure
Sx 4 - 12º after exposure, last ~ 24º
“flu-like “ syndrome
– Respiratory: Cough, SOB, Chest tightness
– Constitutional: fever, chills, malaise,
myalgias
– Signs: fever, tachypnea, tachycardia, insp.
crackles
**Recurrent Sx should increase suspicion**
 Hypersensitivity
Pneumonitis
•
Clinical Presentation
Subacute: less intense, more
prolonged exposure
Sx: insidious, don’t
necessarily coincide with
exposures
Chronic cough, DOE, fatigue,
malaise, anorexia, wt. loss
**May progress to chronic with
continued exposure**
 Hypersensitivity
Pneumonitis
Clinical Presentation
Chronic HP
• Result of untreated/undiagnosed
subacute Dz
• Indistinguishable from IPF
• Irreversible lung fibrosis
• May have RHF Sx, severe
hypoxemia and clubbing (poor
prognostic indicator)
 Hypersensitivity
Pneumonitis
PFT’s
• Acute HP: RESTRICTIVE
– Reduced DLCO
– Rest/exertional hypoxemia
– Resolve within 4-6 weeks after exposure
• Subacute/Chronic: RESTRICTIVE or
OBSTRUCTIVE or MIXED
– Reduced DLCO
– Rest/exertional hypoxemia - may be severe
– + methacholine challenge (22-60%)
**”COPD” in NON-smoker - Think HP!!**
 Hypersensitivity
Pneumonitis
•
Radiography
Acute/Subacute
Fine micronodular pattern or diffuse
ground glass (may be normal with mild
Dz)
Resolves in 4-6 weeks
• Chronic
Fibrosis: linear reticular opacity,
volume loss, honeycombing
May see only ground glass in some sub-
acute/chronic Dz: ? Reversible?
**CT more sensitive than CXR**
 Hypersensitivity
Pneumonitis
Diagnosis
Major
1. Exposure to offending Ag (Hx, measured,
Abs)
2. Compatible Sx several hours after exposure
3. *Abnormal CXR
Minor
1. Bibasilar crackles
2. Reduced DLCO
3. Desaturation (rest/exertion)
4. *Compatible histology
5. + provocation test
 Hypersensitivity
Pneumonitis
Diagnosis
• Detailed Hx/PE
• High Resolution CT
• Complete PFT’s
• Precipitant Abs: only helpful if +
(confirms exposure)
• FOB w/ BAL and TBBx
– Lymphocytes (CD4/CD8<1.0)
– Loose granuloma
**High Index of Suspicion Important**
 Hypersensitivity
Pneumonitis
Treatment
• Antigen Avoidance
• Corticosteroids
– Acute severe attacks
– 60 mg/day, taper at 4 weeks if PFT/Sx
improved
– Improve acute Sx, don’t alter long term
outcome
– Inhaled CS: Sx SOB, cough, Chest tightness
• Prevention
– Avoidance
– Ventilation
– Respirator (air powered “Papper” hood)