Occupational lung disease

occupational lung disease


Occupational asthma - Two types of OA

• OA with latency (more common)
• Immune sensitization
• LMW compounds or not IgE mediated
• Isocyanates - auto body shops; paint, upholstery, glues
• Anhydrides
• Wood dusts
• Metals
• HMW compounds or IgE mediated
• Animal Products
• Plant products
• Biologic enzymes
• OA without latency
• Non-allergic irritant mediated
• RADS (Reactive airways Dysfunction Syndrome) (high incidence in 9-11 first responders)
• Chlorine and ammonia

         peak flows in OA (days 8-10 = weekend)

Interstitial Lung Disease: 

• Pneumoconiosis
• Silicosis simple or progressive massive fibrosis (PMF)
• inc. risk for TB & lung cancer
• may occur with SLE and cause PMF = Caplan's Syndrome
• occupational exposures
• Mining
• Quarrying
• Tunneling
• Stone cutting
• Abrasive blasting
• Glass manufacture
• Ceramics
• Coal Workers Pneumoconiosis
• coal dust macule = macs filled with coal dust
• COPD common
• radiology similar to silicocic - nodules - upper lobe predominance
• Caplan's syndrome
• Asbestosis - 
  • Mining
  • Construction
  • Ship yard work
  • Automobile repair: brake linings
• Parenchymal:
• Asbestosis -late
• Lung Cancer - late
• Rounded Atelectasis
• local area of pleural thickening
• Pleural:
• Benign Asbestos Related Pleural Effusion - early
• Pleural Plaques - early or late
• Pleural Thickening
• Malignant Mesothelioma - late
• Granulomatous Diseases:
• Chronic Beryllium Lung Disease - common in NM
• Hypersensitivity Pneumonitis - 
• Most common
• • Farmers Lung (thermophilic actinomyces) - fungi in hay
  • Pigeon fanciers’ Disease (avian proteins) - feather proteins
  • Humidifier’s Lung (thermophilic actinomyces) 
  • "hot tub lung" - mycobacteria in indoor hot tubs
  • swamp cooler lung
• path = sarcoid like granulomas

Occupational Thoracic Malignancies

• Lung Cancer
• cadmium
• chromium
• radon # 1 cause of environmental cancer
• beryllium
• asbestis
• Mesothelioma

Lung Diseases

Lung Diseases

• Interstitial Pneumonia
• – Reticulonodular pattern
• – Peribronchial thickening
• Viruses, Mycoplasma pneumoniae, Pneumocystis carinii
• Bronchopneumonia 
• – Patchy inhomogeneous consolidation
• – Several lobes involved
• Common organisms:
• S. aureus, E coli, Pseudomonas aeruginosa, Anaerobes, Hemophilus influenzae
• Lobar Pneumonia
• – Predominately one lobe
• – Consolidation crosses segmental boundaries
• Common organisms:
• S. Pneumoniae, Klebsiella pneumoniae, Legionella Pneumophila
• Nodular Pneumonia
• Chronic Pneumonia/Recurrent
• Etiology of Chronic Pneumonia
• Mycobacteria
• Tuberculosis and non-tuberculous
• Fungus
• Chronic aspiration pneumonia
• Post-obstructive pneumonia
• Foreign body
• Tumor
• Not pneumonia

Anatomical Sites of TB Infection

• Lung 80-85%  (nl route of infection)
• Extrapulmonary
• – Lymph nodes
• – Pleura
• – Bones and joints
• – GU system
• – Central nervous system

Tx

long duration = only kill during organisms reproductive cycle

Fungal Infection = Mycoses

• Coccidioidomycosis
• Valley fever (central California)
• CXR - lots of calcified little spots
• 
  
• Histoplasmosis
• Ohio river valley
• CXR - same as Cocci
• more virulent than Cocci
• complication = fibrosing mediastinum
• Blastomycosis
• muddy bogs - Southeast Southcentral
• clinically same as other mycoses

Pleural Effusions

Pleural Diseases

• Pleural fluid 
• Originates from systemic (mainly bronchial) vessels of pleural membranes
• Approximately 15 ml per hemithorax is formed every 24 hours
• Usually has a low protein and low wbc with predominance of macrophages
• Makeup is markedly altered in disease states
• Increased fluid entry
• Increase in permeability of membrane
• Increase in microvascular pressure outside the membrane
• Decrease in intra-pleural pressure
• Atelectasis of the lung
• Decrease in plasma oncotic pressure
• Decreased fluid exit
• Inflammation due to infection, tumor or pulmonary infarct
• Direct infiltration of lymphatics by tumor or infection

Pleural fluid studies

• All effusions: Total protein, LDH, glucose, cell count and differential
• If infection is in differential: cultures and stains (bacterial, mycobacterial and fungal).
• If infection or malignancy is suspected: pH which should be collected in a blood gas syringe (heparinized) on ice and run as soon as possible.
• Cytology if malignancy is in the differential

Transudate vs. exudate

pressure/oncotic imbalance vs inflammation

transudative pleural effusions

• Result from imbalances in hydrostatic and oncotic pressures in the chest rather than local inflammation
• As they result from systemic processes, they are frequently bilateral
• Are rarely the result of primary pulmonary pathology

Causes of transudative effusions

• Increased venous hydrostatic pressure
• – Congestive heart failure; right or left sided  
• Pericardial disease
• Hypoalbuminemia (nephrotic syndrome, liver disease)
• – Decreased intravascular oncotic pressure
• Leakage of ascites or peritoneal dialysate through the diaphragm into the pleural space.
• Treatment of hepatic hydrothorax is aimed at ascites management rather than drainage of pleural fluid
• Hypothyroidism
• Endobronchial obstruction with atelectasis
• Decreased intrapleural pressure
• ? Pulmonary embolism

Exudative pleural effusions = inflammation

• Result from inflammatory processes of the lung or pleural space.
• Present more of a diagnostic dilemma
• – 30% may remain undiagnosed despite repeated studies
• Causes of exudative effusions
• • Infection
• • Pulmonary embolism
• • Malignancy
• • Collagen vascular disease
• – Systemic Lupus, Rheumatoid Arthritis
• Subdiaphragmatic inflammation
• – Pancreatitis
• – Liver abscess
• – Spontaneous bacterial peritonitis
• • Drug reactions
• • Hypothyroidism
• • Prior asbestos exposure

Parapneumonic effusions

• Occur frequently in patients with bacterial pneumonia

if cultures are positive or frank pus is present, an “empyema”

– Pneumococcus most common organism

– Anaerobes and staphylococci also occur frequently

Tuberculous pleural effusions

• Usually not a direct infection of the pleural space, 

but an immunologic reaction to new tuberculous infection

– Exudative effusion with lymphocytic predominance and moderately low glucose

Malignant pleural effusions

• As prognosis is generally poor, management is aimed at palliation

Pulmonary embolism

• Small exudative pleural effusions occur frequently with PE

Pleural Fibrosis

• Usually results from large amounts of 
  • undrained infection or blood in pleural 
  • space
• May also occur with tumor
• May result from asbestos exposure
• Heals with progressive thickening of 
  • pleura
• Some cases are idiopathic
• May result in “trapped lung”

Pulmonary Edema

It is less confusing to think of the colloid osmotic pressure as a positive number with a minimum value of zero (NO PROTEIN).

When the rate of fluid filtration from the capillary 

into the interstitium is the rate of lymphatic 

removal and evaporation - no net fluid 

accumulation.

• However, when the rate of fluid filtration from the 

capillary into the interstitium is > the rate of 

lymphatic removal and evaporation - there is net 

fluid accumulation PULMONARY EDEMA.

Cardiogenic Pulmonary Edema

In a normal lung, the driving force for fluid filtration is 

~1 mmHg

• If in CHF the pulmonary capillary pressure increases 

to ~25 mmHg

• Assuming that at least initially Pi ~ 8 mmHg, plasma 

protein osmotic pressure is ~28 mmHg, interstitial 

fluid protein osmotic pressure is ~14 mmHg, and 

remains 0.98

• Then [(25 8) 0.98(28 14)] = ~ 19 mmHg

Treatment for pulmonary edema

• Decrease Preload: diuretics, sit patient up in bed, n
  • itrates, morphine, dialysis.
• Improve Cardiac Performance: Nitrates, Inotropes, 
  • Digoxin.
• Decrease Afterload: ACE inhibitors, nitroprusside
• Increase Pi: Continuous positive airway pressure, 
  • mechanical ventilation
• Decreasing LpA, or osmotic pressure has not been 
  • attempted.

Non-cardiogenic Pulmonary Edema

If there is endothelial damage Lp

increases and Jv increases

Capillary endothelium loses barrier function

– Does not require change in hemodynamics

– Forces that oppose Pc decrease

– LpA increases

– leaky capillaries and increased fluid filtration!

Treatment of non-cardiogenic pulmonary edema

Treatment / Removal of offending source (infection , aspiration , inhalation)
• Mechanical Ventilation if necessary (with low tidal volumes)
• Many experimental therapies (antiinflammatory among others)


DDx Cardiogenic versus Non-cardiogenic


Underlying condition: Myocardial infarction vs. severe infection
• X-ray appearance
• Estimates of Pc (central venous pressure, BNP peptide)
• Measurement of Pc (Swann-Ganz Catheter)
• Measurement of Alveolar protein concentration (estimate of πi)


Hanta virus = both cardiogenic and non-cardiogenic pulmonary edema

High altitude pulmonary edema (HAPE)

• cardiogenic = pulm venoconstriction
• non-cardiogenic = protein in alveolar fluid

Pulmonary Embolism

Pulmonary Embolism

Swan-Ganz catheter in pulmonary hypertension:  sign of decreased cardiac outout is reduced mixed venous O2.  (Fick principle)

metamphetamine cause of Pulmonary HTN

Pulmonary Embolism


Classic: Stasis, Hypercoagulability and 
endothelial damage (Virchow’s triad)
• Now thought of as acquired or congenital
• Congenital: Thrombophilia (Factor V Leiden, 

Thrombin gene mutations, protein C&S 

deficiency, AT III deficiency)
• Acquired: Immobility of Lower Extremities, 

Surgery (esp. orthopedic of LE), trauma, stroke, 

heart failure, medical illness, critical illness, 

pregnancy, exogenous estrogens, malignancy, 

inflammatory disorders, nephrotic syndrome, 

APLA, smoking, age.

Clinical Signs

• 

Pulmonary: Increased 

respiratory rate, 

Hypoxemia, Crackles, 

Pleural friction rub

• Cardiac: Tachycardia,

hypotension, Right sided 

S4, Elevated jugular 

venous pressure, Increased 

P2.

• Extremities: Leg swelling,

redness. 

Well’s Criteria for PE

• Clinical Signs and Symptoms of DVT? Yes +3
• PE Is #1 Diagnosis, or Equally Likely Yes +3
• Heart Rate > 100? Yes +1.5
• Immobilization at least 3 days, or Surgery in the Previous 4 weeks Yes +1.5
• Previous, objectively diagnosed PE or DVT? Yes +1.5
• Hemoptysis? Yes +1
• Malignancy w/ Treatment within 6 mo, or palliative? Yes +1
• Score interp: <2 points 3.4% chance of PE
• 2-6 points 27.8% chance of PE
• >6 point 78% chance of PE

Diagnostic Tests for PE

• D-dimer and dead-space measurement
• Assessment of lower extremities for DVT
• Ventilation / Perfusion Scanning  (gives probability answer)
• CT angiography of pulmonary arteries = most commonly done test (yes or no answer)
• MRI thorax for PE
• Pulmonary Angiography - no advantage over CT angio

Treatment of PE

• 

Anticoagulation with heparin 

or Low Molecular Weight 

Heparin or Fondaparinux 

then coumadin
• Removal of aggravating

cause when possible

• Thrombolysis for

hemodynamically unstable 

patients

• IVC filters in cases of LE

DVT in patients who cannot 

be anti-coagulated

Lung Development

Lung Development


LUNG DEVELOPMENT
• Embryonic - 3-8 weeks (3-6)

• vascular connection with right atrium
• bronchi develop

• Pseudoglandular 5-17 weeks (6-16)

• peritoneal cavities close
• continued branching
• smooth muscle develops
• terminal buds
• vascularization

• Canalicular 16-26 weeks (16-26)

• capillaries close to alveoli
• surfactant produced
• survival possible at end of this stage
• complex histo

• Saccular 24-37 weeks (26-36)

• first true alveoli
• type I cells flatten = thin
• complex histo
• more surfactant

• Alveolar 36 weeks – 3 years+

• septation of alveli
• 85% of alveoli form postnatally

Airway Development

• 4wk Primitive epithelial cells
• 8wk Neuroendocrine cells appear
• mitogenic
• 10-12wk Presecretory and preciliated 
• 14wk Ciliated cells, neuroepithelial bodies
• mosh pit - move particle to upper airways
• 16wk Goblet (make mucus), serous, basal
• 20-22wk Pre-clara
• 24wk Type I and Type II
• 24-26wk Clara
• detoxify
• regenerate epithelium

Pulmonary circulation

• controlled by VEGF

Bronchial circulation

• branch of aorta

Lymphatic circulation

Barrier Function

• Anatomical-branching
• Ciliated cells
• Mucous cells
• Innate immune function – TOLL-like receptors
• TLRs activated by TGF beta to activate macrophages
• Adaptive immune function

Lung in utero

Pulmonary

• Lung fluid production
• Fluid filled condensed alveoli
• Intermittent fetal breathing movements
• Placenta is the site of gas exchange
• Low PaO2  "Mt. Everest in Utero"

Cardiac

• High pulmonary vascular resistance - collapsed & hypoxic
• Lungs receive 5-10% of cardiac output
• Cardiac circulation shunts past the lung
• Foramen ovale RA-LA
• Ductus venosus - bypass liver
• Ductus arteriosus - bypass lungs

Lungs Post-natally

• Pulmonary
• Lung fluid production stops and fluid is 
• actively resorbed
• Air filled expanded alveoli
• Continuous breathing movements
• Lung is the site of gas exchange
• High PaO2
• Cardiac
• Low pulmonary vascular resistance
• Lungs receive 100% of cardiac output
• Cardiac circulation shunts close
• Foramen ovale closes due to pressure 
• Ductus venosus constricts 
• Ductus arteriosus constricts and obliterate after several days - becomes ligamentum arteriosum

Aging

• Decrease in:
• Static elastic recoil of the lung
• Compliance of the chest wall (but increase
  • in lung compliance)
• – Strength of respiratory muscles
• – Oxygenation (but not carbon dioxide)
• – Respiratory response to hypoxia and
  • hypercapnea

Physical changes in the lung 

with aging

• Cellular-more neutrophils, fewer 
  • macrophages
• Higher elastin/collagen (more lung 
  • compliance)
• Spinal osteoporosis with loss of 
  • height and decrease in lung volume
• Airspace enlargement (senile 
  • emphysema)

Abnormalities of Prenatal 

Lung Growth

• Embryonic-Tracheoesophageal Fistula
• Pseudoglandular-Congenital Diaphragmatic Hernia
• • intestines into thorax = lung hypoplasia
• Canalicular-Pulmonary hypoplasia, 
  • Surfactant deficient lung disease of 
  • prematurity
• • amnioyic fluid = urine
• • IRDS
• • don't have adequate surfactant

• babies are obligate nose breathers

Clinical Signs of Respiratory 

Distress Syndrome

• Grunting
• Flaring
• Retracting
• Increased respiratory rate 
  • to increase minute 
  • ventilation

Chronic Lung Diseases

Bronchopulmonary Dysplasia (BPD)

• after IRDS
• Defined as oxygen requirement at 28 
• days or 36 weeks

Persistent Pulmonary Hypertension

• Right to left shunting at the ductus arteriosis
  • (PDA) and foramen ovale
• Decreased pulmonary blood flow
• Marked hypoxemia