MED - Interstitial Lung Disease , Final Sept08

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Interstitial Lung Disease and Occupational/Environmental Lung Diseases

Gary N. Carlos, MD, FPCP, FPCCPSection of Pulmonary Medicine Department of Internal Medicine

Outline Definition Pathogenesis Classification Clinical

manifestations Natural history of disease Diagnosis Treatment Prognosis


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?


small area, space, or gap in the substance of an organ or tissue. The in betweens

Disease in the in betweens Bronchi Alveoli Blood


Normal Lung AnatomyA. 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 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 tissuesHarrisons 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 patternsGranulomatous lung diseaseT

lymphocytes, macrophages, epithelioid cells

Inflammation and fibrosis

PathogenesisAntigenic StimulationAcute Injury

Air spaces Alveolar walls Interstitium Vascular Lymphatic


Granuloma Fibrosis

Classification (Clinical and Histological)

Major Categories of Alveolar and Interstitial Inflammatory Lung DiseaseLung Response: Alveolitis, Interstitial Inflammation, and FibrosisKNOWN CAUSE Asbestos Fumes, Gases Drugs (Antibiotics, amiodarone, gold) and chemotherapy drugs UNKNOWN CAUSE Idiopathic interstitial pneumonias Idiopathic pulmonary fibrosis ( usual interstitial pneumonia) Desquamative Interstitial Pneumonia Respiratory bronchiolitis-associated interstitial lung disease Acute Interstitial Pneumonia (diffuse alveolar range) Cryptogenic organizing pneumonia (bronchiolitis obliterans with organizing pneumonia) Nonspecific interstitial pneumonia Connective Tissue Diseases Syrematic lupus erythematous, rheumatoid arthritis , ankylosing spondylitis systemic sclerosis, Sjogrens syndrome, polymyositis-dermatomyositis Pulmonary hemorrhage syndromes Goodpastures syndrome, idiopathic pulmonary hemosiderosis, isolated pulmonary capillaritis Pulmonary alveolar proteinosis Lymphocytic infiltrative disorders (lymphocytic interstitial pneumonitis assoc. with connective tissue diasese Eosinophilic Pneumonia Lymphangiooleimyomatosis Amyloidosis Inherited Diseases Tuberous sclerosis, neurofibromatosis, Niemann-Pick disease, Gauchers Disease, Hermansky-Pudlak syndrome Gastrointestinal or liver diseases (Crohns disease, primary biliary cirrhosis, chronic active hepatitis, ulcerative colitis) Graft-vs-host disease (bone marrow transplantation; solid organ transplantataion) Radiation Aspiration Pneumonia Residual of adult respiratory distress syndrome

Lung Response: GranulomatousKNOWN CAUSE Hypersensitivity penumonitis (organic dusts) UNKNOWN CAUSE Sarcoidosis Langerhans cell granulomatosis (eosinophilic granuloma of the lung) Granulomatous vasculitides Wegeners granulomatosis, allergic granulomatosis of Churg-Strauss Bronchocentric granulomatosis Lymphomatoid granulomatosis Inorganic dusts: beryllium silica

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?


KnownPrimary disease Occupational / Environment Drugs / Poisons / Infections

Unknown KnownPrimary disease Occupation / Environmental Drugs / Poisons / infections



What symptoms will I experience? What are the reasons for consultation.


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


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


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


Sarcoidosis ILD with CTD Lymphangioleiomyomatosis (LAM) PLCH Inherited forms of ILD


than 50 years

Idiopathic Pulmonary Fibrosis (IPF)

Gender Premenopausal


LAM, tuberous sclerosis

Female preponderanceLymphocytic interstitial pneumonitis ILD in Hermansky-Pudlak syndrome Connective Tissue Disease



Pneumoconiosis Rheumatoid arthritis

Smoking History Current

or former smokers

IPF, pulmonary histiocytosis X, Desquamative interstitial pneumonitis Respiratory bronchiolitis Never Active

smokers smoking

Sarcoidosis, HP Goodpasture's syndrome

Prior medication use Over

the counter medications

Oily nose drops Petroleum products Amino acid supplements



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 Exposuresdusts, gases, chemicals duration, degree, latency

Physical Examination

Physical exam

Not specific Usual

Tachypnea Bibasilar end inspiratory crackles Late inspiratory high pitched rhonchi Wheezing (uncommon) Cyanosis and clubbing pulmonary hypertension Cor pulmonale


Physical exam Findings

supportive of underlying disease / multi organ


Laboratory examination

Chest Imaging Studies

Chest radiograph

Bibasilar reticular pattern Nodular or mixed pattern of alveolar filling HoneycombingLate 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 Hypersensitivity precipitin panel, serum precipitins Antineutrophil cytoplasmic & antibasement membrane Ab (vasculitis) anti-IG Ab, circulating immune complex CRP, ESR Serum ACE level (sarcoidosis)

Environmental exposure

Systemic vasculitis


Tissue / Cellular examination Bronchoscopy

Bronchio-alveolar lavage Transbronchial biopsy


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 or distribution of cellular reaction type of inflammatory or effector

Abundant inflammatory cells(early phase) Less cells, abundant fibrosis (late phase) Collection of cells in alveoli (early alveolitis)




Many lymphocytes, eosinophils and PMNs (better response to corticosteroid therapy)


Is there a treatment for it?

Principles of treatment Major


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 0.5-1 mg/kg 0.25-0.5 mg/kg



of treatment

4-12 weeks -> re evaluated -> tapered

Treatment Cyclophosphamide Azathioprin Methotrexate Colchicine Penicillamine Cyclosporine


Other medicalManage 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



(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



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


of work related pulmonary disease

Impairment Disability Workers compensation Impairment objectively determined abnormality of functional assessment Disability inability to perform specific task owing to the impairment


Clinical History Most

important Detailed occupational historyPotential exposure in the workplace Specific

contaminants involved

Availability of personal respiratory protection device Specific contaminant Ventilation

in the workplace Size of particles


above 10-15 microns

Do not penetrate the upper airways Little or no role in chronic respiratory disease


below 10 microns

Deposited below the larynx Fossil fuels, high temperature industrial processes Coarse

mode fractions (2.5-10microns) Fine or accumulation mode fractions(


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