Med - Interstitial Lung Disease , Final Sept08

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  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. 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  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 Air spaces Alveolar walls

Antigenic Stimulation

Interstitium Vascular Lymphatic

Acute 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 Connective Tissue Diseases Syrematic lupus erythematous, rheumatoid arthritis , ankylosing spondylitis systemic sclerosis, Sjogren’s syndrome, polymyositis-dermatomyositis

Tuberous sclerosis, neurofibromatosis, Niemann-Pick disease, Gaucher’s Disease, Hermansky-Pudlak syndrome Gastrointestinal or liver diseases (Crohn’s disease, primary biliary cirrhosis, chronic active hepatitis, ulcerative colitis) 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 – – – – –

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

 Older –

years

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 – – –

Oily nose drops Petroleum products Amino acid supplements

 Illicit – –

the counter medications

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 –



Environmental exposure –



Hypersensitivity precipitin panel, serum precipitins

Systemic vasculitis – –



ANA, RF

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 – –

Abundant inflammatory cells(early phase) Less cells, abundant fibrosis (late phase)

 Pattern –

of cellularity or distribution of cellular reaction

Collection of cells in alveoli (early alveolitis)

 Predominant

cell –

type of inflammatory or effector

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 – –



Alternative sources of exposure – – –

 

Work Symptoms 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 –



Lung Cancer – – –



Diffuse interstitial fibrosing disease (pulmonary fibrosis) of the lung directly related to intensity and duration of exposure 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 

–

PE 

–

Fibrotic changes-lower lobes and subpleural areas

PFT 



Inspiratory crackles, digital clubbing

CXR and HRCT 

–

Progressive dyspnea, cough, chest pain

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/diseaseinfo/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

John Powell

You cannot dream yourself into a character; you must hammer and forge yourself one James Froude