Interstitial Lung Disease and

Occupational/Environmental
Lung Diseases

Gary N. Carlos, MD, FPCP, FPCCP

Section of Pulmonary Medicine
Department of Internal Medicine
Outline

 Definition
 Pathogenesis
 Classification
 Clinicalmanifestations
 Natural history of disease
 Diagnosis
 Treatment
 Prognosis
Objectives:

 What are Interstitial Lung Diseases? Occupational

Lung Diseases
 What causes it?
 What are the symptoms?
 Am I at risk? Who are at risk?
 How will I know that its an ILD?
 Is there a treatment for it?
 What will happen if I am not treated? What are the
complications?
 What do I expect from the disease and with
treatment?
What are Interstitial Lung
Diseases?
Interstitium

A small area, space, or gap in the substance

of an organ or tissue.
 The in betweens
– Disease in the in betweens
 Bronchi
 Alveoli
 Blood vessels
Normal Lung Anatomy

A. Septum
B. Pulmonary
A
C. Alveolar
duct
D. Pleura
E. Alveolar
sac
F. Pulmonary
v
Interstitial Lung Disease

 Wide variety of disorders

> 200 clinical conditions

 Diffuse parenchymal lung diseases (DPLD)

Interstitial Lung Diseases

 Heterogeneous group of lung disorders that

are classified together because of similar
clinical, roentgenographic, physiologic or
pathologic manifestations
 Misnomer. Associated with extensive alveolar
and airway architecture
Interstitial Lung Diseases

 Represents a large number of conditions that

involves the parenchyma of the lungs
(alveoli, alveolar epithelium), the capillary
endothelium, spaces between these
structures, as well as the perivascular and
lymphatic tissues

Harrison’s 05
What causes it?
Pathogenesis

 Multipleinitiating events
 Precise pathway from injury to fibrosis not
known
 Postulated common pathway
– Acute injury to the lung parenchyma
– Chronic interstitial inflammation?
– Fibroblast activation and proliferation
– Pulmonary fibrosis and tissue destruction
Pathogenesis

 Immunopathogenic responses are limited

 Two major histopathologic patterns
– Granulomatous lung disease
T lymphocytes, macrophages, epithelioid cells
– Inflammation and fibrosis
Pathogenesis

Air spaces
Antigenic Alveolar walls
Stimulation
Interstitium
Acute
Vascular
Lymphatic
Injury

Inflammation

Granuloma

Fibrosis
 Classification
(Clinical and Histological)
 Major Categories of Alveolar and Interstitial Inflammatory Lung Disease
Lung Response: Alveolitis, Interstitial Inflammation, and Fibrosis
KNOWN CAUSE

Asbestos Radiation

Fumes, Gases Aspiration Pneumonia

Drugs (Antibiotics, amiodarone, gold) and chemotherapy drugs Residual of adult respiratory distress syndrome

UNKNOWN CAUSE
Idiopathic interstitial pneumonias Pulmonary alveolar proteinosis

Idiopathic pulmonary fibrosis ( usual interstitial pneumonia) Lymphocytic infiltrative disorders (lymphocytic interstitial pneumonitis assoc. with
connective tissue diasese

Desquamative Interstitial Pneumonia Eosinophilic Pneumonia

Respiratory bronchiolitis-associated interstitial lung disease Lymphangiooleimyomatosis

Acute Interstitial Pneumonia (diffuse alveolar range) Amyloidosis

Cryptogenic organizing pneumonia (bronchiolitis obliterans with organizing pneumonia) Inherited Diseases

Nonspecific interstitial pneumonia Tuberous sclerosis, neurofibromatosis, Niemann-Pick disease, Gaucher’s Disease,
Hermansky-Pudlak syndrome

Connective Tissue Diseases Gastrointestinal or liver diseases (Crohn’s disease, primary biliary cirrhosis, chronic active
hepatitis, ulcerative colitis)

Syrematic lupus erythematous, rheumatoid arthritis , ankylosing spondylitis systemic Graft-vs-host disease (bone marrow transplantation; solid organ transplantataion)
sclerosis, Sjogren’s syndrome, polymyositis-dermatomyositis

Pulmonary hemorrhage syndromes

Goodpasture’s syndrome, idiopathic pulmonary hemosiderosis, isolated pulmonary

capillaritis

Lung Response: Granulomatous

KNOWN CAUSE

Hypersensitivity penumonitis (organic dusts) Inorganic dusts: beryllium silica

UNKNOWN CAUSE

Sarcoidosis Bronchocentric granulomatosis

Langerhan’s cell granulomatosis (eosinophilic granuloma of the lung) Lymphomatoid granulomatosis

Granulomatous vasculitides

Wegener’s granulomatosis, allergic granulomatosis of Churg-Strauss

Major histopathologic forms
 Desquamative Interstitial Pneumonia (DIP)
 Respiratory Bronchiolitisis ILD (RBILD)
 Acute Interstitial Pneumonitis / Hamman-Rich Syndrome
 Non specific interstitial pneumonia (NSIP)
 Cryptogenic Organizing Pneumonia (COP)
 Lymphocytic Interstitial Pneumonia (LIP)
 Hypersensitivity Pneumonitis
 Sarcoidosis
 Pulmonary Langerhans Cell Histiocytosis (PLCH)
 Tuberous sclerosis
 lymphangioleiomyomatosis
Major histopathologic forms

 Provides clues to etiology, pathogenesis,

natural history, and prognosis
 Not free standing diagnostic entities
– Each limits your differential diagnosis
– Each has specific implications concerning likely
treatment response and outcome
How to approach it?

 Granulomatous
 Known
– Primary disease
– Occupational / Environment
– Drugs / Poisons / Infections
 Unknown
 Fibrosis
 Known
– Primary disease
– Occupation / Environmental
– Drugs / Poisons / infections
 Unknown
What symptoms will I experience?

What are the reasons for

consultation.
CLINICAL PRESENTATION

 Wide variety of disorders

 Signs and symptoms are very similar
 Problems usually vague and develop
gradually
 May be attributed to aging, being overweight,
out of shape or residual effects of an URTI
 SSx are common with wide range of medical
conditions
CLINICAL PRESENTATION

 Progressive breathlessness
 Persistent non productive cough
 Abnormal radiograph
 Pulmonary symptoms associated with
another disease
 Abnormality on simple spirometry
SYMPTOMS

 Dyspnea
 Cough
– Fatigue
– Weight loss

– Chest pain
– Hemoptysis
– Wheezing
Clinical Manifestations

 Acute
 Subacute
 Chronic
Symptoms

 May be secondary to the primary disease

 Clinical findings consistent for CTD
Musculoskeletal pain
Weakness
Fatigue
Fever
Joint pains or swelling
Photosensitivity
Raynaud's phenomenon
Pleuritis
Who are affected?

Who are at risk?

 Age at presentation

 20-40 years
– Sarcoidosis
– ILD with CTD
– Lymphangioleiomyomatosis (LAM)
– PLCH
– Inherited forms of ILD
 Older than 50 years
– Idiopathic Pulmonary Fibrosis (IPF)
Gender
 Premenopausal women
LAM, tuberous sclerosis
 Female preponderance
Lymphocytic interstitial pneumonitis
ILD in Hermansky-Pudlak syndrome

Connective Tissue Disease

 Male preponderance
Pneumoconiosis
Rheumatoid arthritis
Smoking History

 Current or former smokers

IPF, pulmonary histiocytosis X,
Desquamative interstitial pneumonitis
Respiratory bronchiolitis
 Never smokers
Sarcoidosis, HP
 Active smoking
Goodpasture's syndrome
Prior medication use

 Over the counter medications

– Oily nose drops
– Petroleum products
– Amino acid supplements
 Illicit drugs
– Heroine
– Methadone
Family History

 Autosomal dominant pattern

– Idiopathic pulmonary fibrosis
– Sarcoidosis
– Tuberous sclerosis
– Neurofibromatosis
 Autosomal recessive pattern
– Niemann-Pick disease
– Gaucher's disease
– Hermansky-Pudlak syndrome
Occupational and Environmental
History

 Lifelong employment history

– Specific duties / job description
– Problems with co workers
– Summer jobs?
– Use of protective devices
– Exposures
 dusts, gases, chemicals
 duration, degree, latency
Physical Examination
Physical exam

 Not specific
 Usual
– Tachypnea
– Bibasilar end inspiratory crackles
– Late inspiratory high pitched rhonchi
 Wheezing (uncommon)

 Late
– Cyanosis and clubbing
– pulmonary hypertension
– Cor pulmonale
Physical exam

 Findings supportive of underlying disease

 Extra-pulmonary / multi organ

Laboratory examination
Chest Imaging Studies

 Chest radiograph
– Bibasilar reticular pattern
– Nodular or mixed pattern of alveolar filling
– Honeycombing
 Late finding
 Poor prognosis
 Clinical correlation is poor
 Other conditions may mimic ILD
– Congestive Heart Failure
– Atypical pneumonia
– Lymphangitic spread of cancer
 May be normal in 10% of patients
Chest Imaging Studies

 CT Scan (HRCT)
– More sensitive and superior for early detection
– Better assessment of extent and distribution
– Better in evaluating possible co-existing disease
– Can be helpful in determining the most
appropriate site for biopsy
– Patterns usually follow same findings on chest
xray / disease
 Pulmonary Function Test

 Spirometry: restrictive pattern

– May be absent or masked in the presence of concomitant
obstructive lung disease
 Diffusion Capacity: generally reduced DLCO
 Static compliance: reduced
 Pulmonary exercise testing: decrease exercise
capacity; impaired ventilation and gas exchange
 ABG: normal or hypoxemic; respiratory alkalosis
Blood / Serum

 Connective tissue disease

– ANA, RF
 Environmental exposure
– Hypersensitivity precipitin panel, serum precipitins
 Systemic vasculitis
– Antineutrophil cytoplasmic & antibasement membrane Ab
(vasculitis) anti-IG Ab, circulating immune complex
– CRP, ESR
 Sarcoidosis
– Serum ACE level (sarcoidosis)
Tissue / Cellular examination

 Bronchoscopy
– Bronchio-alveolar lavage
– Transbronchial biopsy
 Lung biopsy
 Video Assisted Thoracoscopic Surgery
(VATS)
– Confirms diagnosis
– Assess activity of the disease
– Helps in determining prognosis
Important histologic patterns
 Usual Interstitial Pneumonia (UIP)
 Non specific Interstitial Pneumonia
 Respiratory bronchiolitis
 Bronchiolitis Obliterans with Organizing
Pneumonia (BOOP)
 Desquamative Interstitial Pneumonia
 Lymphocytic Interstitial Pneumonia
 Pattern of diffuse alveolar damage
Histologic features affecting prognosis

 Degree of cellularity
– Abundant inflammatory cells(early phase)
– Less cells, abundant fibrosis (late phase)
 Pattern or distribution of cellular reaction
– Collection of cells in alveoli (early alveolitis)
 Predominant type of inflammatory or effector
cell
– Many lymphocytes, eosinophils and PMN’s
(better response to corticosteroid therapy)
Algorhythm
Is there a treatment for it?
Principles of treatment
 Major goals
– Permanent removal of offending agent

– Early identification and aggressive suppression of

acute and chronic inflammatory process
Treatment

 Glucocorticoids
– Mainstay of therapy
– Success rate low
– No direct evidence that it improves survival
 Dose
– 0.5-1 mg/kg
– 0.25-0.5 mg/kg
 Length of treatment
– 4-12 weeks -> re evaluated -> tapered
Treatment
 Cyclophosphamide
 Azathioprin

 Methotrexate
 Colchicine
 Penicillamine
 Cyclosporine
Treatment
 Other medical
 Manage cough and hyper reactive airways
 Supplemental oxygen, Phlebotomy
 Diuretics and drugs for pulmonary hypertension
 Early control of infections and immunizations
 Lung transplantation
 Non medical
– Smoking cessation
– Regular exercise
– Eat well
– Pulmonary rehabilitation program
Ancillary measures and care

 Patient education
 Nutritional instructions
 Psychological support
 Rehabilitation and body conditioning
 Smoking cessation
Complications

 Hypoxemia (low blood oxygen levels)

 Pulmonary hypertension (high blood
pressure in the pulmonary circulation)
 Cor pulmonale (right sided heart failure)
 Respiratory failure
Interstitial Lung Disease

 Non malignant disorder

 Not caused by definite identified infectious agent
 Multiple initiating agents
 Outcome due to the effects of immunopathogenic
pathogenic responses of the lungs
 Characterized by diffuse parenchymal lung
involvement
 May be primary or secondary
 All develop irreversible scarring
 Progressive derangement of ventilatory function and
gas exchange
 OCCUPATIONAL and
ENVIRONMENTAL LUNG DISEASES
OCCUPATIONAL and ENVIRONMENTAL
LUNG DISEASES

 Diseases for which the environment or

occupation are the suspected cause
 Identification of an environment associated
disease
– Only intervention that might prevent further
significant deterioration
– Lead to patients improved condition
– Primary preventive strategies
OCCUPATIONAL and ENVIRONMENTAL
LUNG DISEASES

 Diagnosis of work related pulmonary disease

– Impairment
– Disability
– Workers compensation
 Define
– Impairment – objectively determined abnormality
of functional assessment
– Disability – inability to perform specific task owing
to the impairment
Clinical History

 Most important
 Detailed occupational history
– Potential exposure in the workplace
 Specific contaminants involved
– Availability of personal respiratory protection
device
– Specific contaminant
 Ventilation in the workplace
 Size of particles
MEASUREMENT OF EXPOSURES

 Particles above 10-15 microns

– Do not penetrate the upper airways
– Little or no role in chronic respiratory disease
MEASUREMENT OF EXPOSURES

 Particles below 10 microns

– Deposited below the larynx
– Fossil fuels, high temperature industrial
processes
 Coarse mode fractions (2.5-10microns)
 Fine or accumulation mode fractions(<2.5)
 Ultrafine fraction (<0.1)
MEASUREMENT OF EXPOSURES

 Coarse mode fractions (2.5-10microns)

– Crustal elements
 Silica
 Aluminum
 Iron

 Fineor accumulation mode fractions(<2.5

microns)
– Potentially carried to the lower airways
 MEASUREMENT OF EXPOSURES

 Ultrafine fraction (<0.1 microns)

– Make up the largest number of particles
– Tend to remain in the airstream
– Deposit on random basis
Clinical History

 Similar symptoms of co-workers

 Temporal association
– Work
– Symptoms
 Alternative sources of exposure
– Home, hobbies
– Exposure to traffic or industrial facilities
– Exposure to second hand smoke
 Actual chemical composition, mechanical properties,
immunogenicity and infectivity of inhaled particles
 Visit to work site
OCCUPATIONAL PULMONARY DISEASE

 Inorganic dust
– Asbestosis
– Silica
– Coal
– Beryllium
– Other metals
 Organic dust
– Cotton dust
– Grain dust
– Agricultural dust
– Other environmental agents
Asbestos

 Generic term for different mineral silicates

 Crocidolite
 Chrysolite
 Amosite
 Anthophyllite

 Clinical manifestations
 Pleural disease: pleural plaques, benign pleural
effusions, pleural fibrosis and malignant mesothelioma
 Asbestosis
Asbestos

 Industries
– Constructions and shipbuilding
 Occupations
– Plumbing
– Pipefitting
– insulating
 Bystander exposure
Asbestos

 Asbestosis
– Diffuse interstitial fibrosing disease (pulmonary fibrosis) of
the lung directly related to intensity and duration of exposure
 Lung Cancer
– Squamous cell or adenocarcinoma
– Higher risk among smokers
– Peaks 15-19 yrs after exposure
 Mesotheliomas
– Pleural or peritoneal
– Not associated with smoking
– Peaks 30-35 yrs after exposure
Asbestosis

 DIAGNOSIS
– History
 Progressive dyspnea, cough, chest pain
– PE
 Inspiratory crackles, digital clubbing
– CXR and HRCT
 Fibrotic changes-lower lobes and subpleural areas
– PFT
 Restrictive
 Treatment
– Supportive
Silica or Crystalline quartz

 Occupations associated with exposure to

silica containing rock and sand
– Construction
– Mining, sandblasting
– Granite quarrying
– Drilling
– Foundry work
Silica or Crystalline quartz

 Clinical manifestations
– Silicosis (Progressive pulmonary fibrosis with exposure and
occurs in a dose-response fashion after many years of
exposure)
– Auto immune connective tissue disorder
– RA, SLE and scleroderma
 Silicotuberculosis (3x)
 COPD and Chronic bronchitis
 Lung cancer
Silicosis
 Fibronodular parenchymal disease (silicotic nodules)
 Frequently without symptoms
 May have acute or accelerated forms which may
lead to respiratory failure
 Chest radiograph
– Small rounded opacities in the upper lobes
– Reticular or irregular densities
– Hilar adenopathy
 Calcification of hilar nodes
 “Egg shell pattern
Coal dust

 Coal mining
– Coal dust; 50% of anthracite miners
– Develop coal macules and focal emphysema
 Coal worker’s Pneumoconiosis
– pneumoconiosis with progressive massive fibrosis
& seropositive rheumatoid arthritis
 Caplan’s syndrome
Coal Dust

 Chest radiograph
– early = reticular: small irregular opacity
– late = nodular: rounded regular opacity
1-5mm
– nodules > 1 cm upper lung in
complicated CWP
– Calcifications are generally not seen
Beryllium

 Berylliosis
– Acute pneumonitis or chronic interstitial
pneumonitis
– Exposure: alloys, ceramics, high-tech electronics,
fluorescent lights production
– Biopsy: granulomatous formation
Inorganic Dust

 SIDEROSIS: iron & iron oxides from welding

or silver finishing
 STANNOSIS: tin oxide used in metallurgy,
color stabilization, printing, porcelain, glass
and fabric
 BARITOSIS: barium sulfate used as catalyst
for organic reactions, drilling mud and
electroplating
Organic Dust

 BYSSINOSIS (Cotton Dust): cotton, flax or

hemp
 GRAIN DUST: grain elevators; farmers,
 FARMER’S LUNG: moldy hay containing
spores of thermophilic actinomycetes; results
to hypersensitivity pneumonitis
References
 Harrison’s Principles of Internal Medicine; Chapter 250 and 255; 17th
edition 2008
 Up to date; Approach to patients with interstitial lung disease; 2008
 Up to date; Idiopathic Interstitial Pneumonias; 2008
 Up to date; Overview of occupational and environmental health; 2008
 The Washington Manual, Pulmonary Medicine Subspecialty Consult;
2006
 http:/www.nationaljewish.org/disease-
info/diseases/rheum/ild/about/index.aspx
 http:/www.clevelandclinicmeded.com/medicalpubs/diseasemanageme
nt/pulmonary/occlung.htm
 http:/www.mayoclinic.com/health/interstitial-lung-disease/DS00592
 http:/www.emedicine.com/med/topic1961.htm
The only real mistake is the one from which
we learn nothing
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