INTERSTITIAL LUNG DISEASE

Definition & Background Interstitial lung disease (ILD) is a common term that includes more than 150 chronic lung disorders. When a person has ILD, the lung is affected in three ways. First, the lung tissue is damaged in some known or unknown way. Second, the walls of the air sacs in the lung become inflamed. Finally, scarring (or fibrosis) begins in the interstitium (or tissue between the air sacs), and the lung becomes stiff. When the interstitium becomes scarred and thickened, it is much more difficult for oxygen to travel from the air into the bloodstream. Patients with interstitial lung disease, then, will develop symptoms which are the result of lung malfunction, like shortness of breath and cough.

-”without” or “with” granulomas The terms interstitial lung disease, pulmonary fibrosis, interstitial pulmonary fibrosis, and diffuse parenchymal lung disease often used to describe the same condition. Classification: “Known” vs. “Unknown” -”without” or “with” granulomas

Examples of Known Etiology: without granulomas ARDS Occupational and environmental inhalants (e.g. asbestos, gases, aerosols) Drugs Aspiration Radiation Lymphangitic spread of carcinoma

Examples of Known Etiology: with granulomas Occupational and environmental inhalants -Beryllium -Hypersensitivity pneumonitis (an allergic disorder) - Talc Infectious agents - AFB (Acid-fast bacillus) - Fungi

Examples of Unknown Etiology: without granulomas Ideopathic Interstitial Pneumonias (IIP): Vasculitis Pulmonary hemorrhage syndromes Eosinophilic infiltration Ankylosising spondylitis

Examples of Unknown Etiology: with granulomas Sarcoidosis Histiocytosis-X ANCA (+) Granulomatos vasculitis -Wegener’s granulomatosis -Churg-Strauss -Lymphomatoid granulomatosis

Clinical Assessment Check medication Employment Systemic Illnesses Exposures

Signs & Symptoms The most common symptoms are shortness of breath with exercise and a non-productive cough. Some patients may also have fever, weight loss, fatigue, muscle and joint pain, and abnormal chest sounds, depending upon the cause. Clubbing can also be seen.

Pulmonary Function Test PFT usually shows a restrictive pattern -The FEV1/FVC ratio is usually normal -It shows reduced lung volumes (low vital capacity, low total lung capacity) Arterial blood gases typically show mild hypoxemia. Patients tend to hyperventilate and have a reduced PCO2 and compensated respiratory alkalosis, mostly as a result of increased respiratory rate.

Check Medications Immunosuppressive or chemo agents - Bleomycin, methotrexate, cyclophosphmide Antibiotics - Macrobid Cardivascular drugs - Amiodarone Vasoactive and neuroactive - Sansert and dilantin

Occupational ILD There are 3 categories of occupational lung disease Hypersensitiviy pneumonitis Organic dusts (byssinosis) Inorganic dusts (asbestosis, silicosis, coal workers’ pneumoconiosis, and berylliosis)

Hypersensitivity Pneumonitis It is an immune-mediated reaction to organic agents Typically it has poorly formed granulomas Diagnosis is by history and chest x-ray may reveal recurrent infiltrates Various causes include: Moldy hay --- “farmer’s lung” Grain dust (works in a grain elevator) Air conditioning systems Hobbies such as bird breeding Best treatment is to remove the patient from the offending antigent. Corticosteroids are beneficial only in acute disease.

Byssinosis Caused by inhalation of cotton, flax, or hemp dust. Not immune-related, no sensitization needed Early stage has occasional chest tightness Late stage has regular chest tightness toward the end of the 1st day of the work week (“Monday chest tightness”) Therapy for early-stage focuses on reversing airway narrowing. Antihistamines may be prescribed to reduce tightness in the chest. Bronchodilators may be used with an inhaler or taken in tablet form. Reducing exposure is essential.

Asbestos exposure Causes parenchymal fibrosis with > 10 years of moderate exposure Features Causes bilateral mid-thoracic pleural thickening/plaque/calcification formation. Chest X-ray shows diaphragmatic calcification with sparing of the costophrenic angle Malignant mesotheliomas are associated (80%) with asbestos exposure Asbestosis results from > 10 years of moderate exposure. Smoking has a synergistic effect with asbestosis in development of lung CA (adeno and squamous)

Asbestosis - Pleural Plaques

This long, thin object is an asbestos fiber

Silicosis Requires years of exposure to crystalline silica to develop (as in mining, glassmaking, ceramics, sandblasting, foundries, and brick yards—with a latency of 20-30 years. Acute form: large exposures to fine particles --- may develop in months, not years Hallmark of chronic forms:=nodules - simple: small nodule <1 cm, usually upper lung zones - not associated with symptoms or pulmonary function changes - complicated: leads to progressive massive fibrosis nodules > 1 cm

Silicosis showing calcified coalescence areas in upper lobes broncholiths 2 mm in diameter showing calcified coalescence areas in upper lobes

Berylliosis Caused by a cell-mediated immune response that can occur from > 2 years exposure to even slight amount of beryllium. Suspect in people working in high-tech electronics, alloys, ceramics, and pre-1950 fluorescent light manufacturing. Affects upper lobes (like silicosis, TB) Have hilar lymphadenopathy that looks identical to that caused by sarcoidosis on chest X-ray. Diagnose by beryllium lymphocyte transformation test. Treat with corticosteroids.

Non-Occupational ILD Idiopathic pulmonary fibrosis (IPF) BOOP (bronchiolitis obliterans organizing pneumonia) Collagen-vascular diseases Sarcoidosis Eosinophilic Granuloma Lymphangioleiomyomatosis (pronounced lim-fan-g-o-lie-o-my-o-ma-toe-sis) Vasculitis causing ILD: Churg-Strauss Goodpasture syndrome Eosinophilic pneumonia

Idiopathic Pulmonary Fibrosis Etiology uncertain (autoimmune?) It is a diagnosis of exclusion Accounts for 50% of ILD’s No extrapulmonary manifestation of the disease Male = female, average age = 55 Smoking worsen disease 10% may have low titers of ANA or RF

IPF presentation Dyspnea and cough and diffuse infiltrative process on CXR Clubbing is common History of progressive exercise intolerance Dry crackles at lung bases Like many ILD’s, PFT’s show a “restrictive” pattern (low TLC, normal FEV1/FVC, low DLCO) Diagnosis: confirmed in about 25% of patients by transbronchial biopsy. If transbronchial biopsy is not sufficient, a thorascopic-guided lung biopsy or open lung biopsy should be done-especially when there is any suggestion that there may be an infection involved or in younger patients. Treatment: corticosteroids + or – cyclophosphamide or azathioprine (20-30% of patients show improvement. This disease progresses to death. Single-lung transplantation is an option for some late-IPF patients. Pneumococcal and influenza vaccines should be given.

Sarcoidosis A disease characterized by the presence of granulomatous tissue. This is a systemic disease which involves eyes, brain, heart, lungs, bones and kidneys, skin, liver and spleen. On pathology a non-caseating granuloma composed of histiocytes, giant cells and lymphocytes. In advanced lung disease fibrotic changes are seen.

Etiology Unknown, likely immunological basis. Clinical Features Four stages are identified: Stage 0: No obvious intrathoracic involvement Stage 1: Bilateral hilar lymphadenopathy, often accompanied by arthritis, uveitis and erythema nodosum. Stage 2: Pulmonary parenchyma is also involved, changes in mid and upper zones. Stage 3: Pulmonary infiltrates and fibrosis without adenopathy.

Stage I (bilateral hilar adenopathy)

Stage II Reticular nodules and BHL

Treatment and Prognosis Pulmonary Function No impairment occurs in stages 0 and 1. In stages 2 and 3 restrictive changes are seen. Treatment and Prognosis 85% of these patients improve spontaneously, but 15% may develop progressive fibrosis and respiratory failure. Prednisone 0.5- 1 mg/kg initially, then tapered and continued for 6 months to 1 year.

Mental Break

Hypersensitivity Pneumonitis Also known as extrinsic allergic alveolitis. Hypersensitivity reaction in the lung occurs in response to inhaled organic dust. Example is farmer’s lung. The exposure may be occupational or environmental. The disease occurs from type III and type IV hypersensitivity reactions. Farmer’s lung is due to thermophilic actinomyces in moldy hay. Bird fancier’s lung is caused by avian antigen.

Pathology There is infiltration of alveolar walls with lymphocytes, plasma cells and histiocytes. There are loosely formed granulomas. Fibrotic changes occur in advanced disease.

Clinical Features Acute Hypersensitivity Pneumonitis The disease may occur in acute or chronic forms. Acute Hypersensitivity Pneumonitis Dyspnea, fever, malaise and cough appear 4-6 hours after exposure. These symptoms continue for 24-48 hours. Physical examination shows fine crackles throughout the lungs. These patients present with progressive dyspnea over a period of years. Chest radiograph may be normal, but may show reticular nodular infiltration.

Chronic Hypersensitivity Pneumonitis These patients present with progressive dyspnea. Physical examination shows bilateral inspiratory crackles. Chest x-ray shows reticular nodular infiltration and fibrosis predominantly in upper lobes. Pulmonary function tests – restrictive pattern. Gas exchange shows hypoxemia which worsens on exercise.

Interstitial Disease Caused by Drugs, Poisons and Radiation Various drugs cause acute pulmonary reaction – proceeding to interstitial fibrosis. These drugs are busulfan, nitrofurantoin, amiodarone, bleomycin. High oxygen concentration – interstitial fibrosis. Radiation exposure – acute pneumonitis – fibrosis.

Bronchiolitis Obliterans Organizing Pneumonia (BOOP) BOOP is bronchiolitis (inflammation of the small airways) and a chronic alveolitis (the organizing pneumonia). In adults, it is associated with penicillamine use. Common presentation is an insidious onset (seeks to 1-2 months), of cough, fever, dyspnea, malaise, and myalgias. Multiple courses of antibiotics without effect. Rales are common. Chest X-ray shows some interstiial disease, bronchia thickening, and patchy bilateral alveolar infiltrate. It has good prognosis and responds to steroids. Open lug biopsy is the definitive means of diagnosing BOOP.

Eosinophilic granuloma Previously called “Histiocystosis X” Smokers; and M > F It sometimes involves the posterior pituitary-leading to diabetes insipidus In the lung, it causes interstitial changes and small cystic spaces in the upper lung fields, both of which are visible on chest X-ray giving a “honeycomb appearance”. 10 % initialy present with a pneumothorax and up to 50% get a pneumothrorax some time in the course of the illness. Diagnosis is made by finding Langerans cells on lung biopsy or bronchoalveolar lavage. Treatment: stop smoking!

Vasculitis which causes ILD Wegener Granulomatosis - “necrotizing granuloma” which: 1. Affects the upper respiratory tract and paranasal sinuses 2. Causes a granulomatous pulmonary vasculitis with large (sometimes cavitary) nodules 3. Causes a necrotizing glomerulonephritis Test: ANCA test (90% sensitive and 90% specific); when positive, it virtually always c-ANCA Diagnosis: confirmed from either a biopsy of the nasal membrane or an open lung biopsy Treatment: cyclophosphamide with or without corticosteroids.

Wegener's Granulomatosis chest x–ray showing bilateral lung nodules CT scan from the same patient

Wegener’s granulomatosis affecting other sites in the body Nasal crusting and frequent nosebleeds can occur. Erosion and perforation of the nasal septum. The bridge of the nose can collapse resulting in a “saddle–nose deformity”. This resulted from the collapse of the nasal septum caused by cartilage inflammation Narrowing of the “windpipe” just below the vocal cords, a condition called “subglottic stenosis”. This narrowing, caused by inflammation and scarring

Churg-Strauss necrotizing small vessel vasculitis with eosinophilic infiltration.” it may affect the skin and kidney, and may cause neuropathy Patients usually presents with preexisting asthma and have eosinophilia (up to 80% of the WBCs!) -Consider this with a progressively worsening asthmatic -Treatment: Aggressive therapy with cytotoxic agents and corticosteroids.

Other ILD’s Goodpasture Syndrome - Autoimmune; young adult males M to F is 3 : 1 - hemoptysis that usually precedes renal abnormalities - May have Fe anemia - Symptoms due to anti-glomerular basement memberrane antibodies which result in linear deposition of IgG and C3 on alveolar and glomerular BM. - Treat with immunosuppressives and plasmapheresis

Idiopathic Pulmonary Hemosiderosis causes intermittent pulmonary hemorrhage It is similar to Goodpasture except IPH does not affect the kidneys Fe deficiency anemia occurs It may remit in young patients, but it is unrelenting in adults.

The End