Interstitial Lung Disease and Occupational/Environmental

Lung Diseases

Gary N. Carlos, MD, FPCP, FPCCP Section of Pulmonary MedicineDepartment of Internal Medicine

Outline

Definition Pathogenesis Classification Clinical manifestations 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. SeptumB. Pulmonary AC. Alveolar ductD. PleuraE. Alveolar sacF. Pulmonary vG. LymphaticsH. Bronchovascular bundle

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

Multiple initiating 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

Antigenic Stimulation

Air spacesAlveolar walls

Fibrosis

InterstitiumVascularLymphatic

Granuloma

Inflammation

Acute

Injury

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 sclerosis, Sjogren’s syndrome, polymyositis-dermatomyositis

Graft-vs-host disease (bone marrow transplantation; solid organ transplantataion)

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

Fine or 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/

diseasemanagement/pulmonary/occlung.htm http:/www.mayoclinic.com/health/interstitial-lung-disease/DS00592 http:/www.emedicine.com/med/topic1961.htm

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