Interstitial Lung Disease

1. Interstitial Lung Disease David S. Goya, DO, FCCP, FACP Kaiser Permanente Medical Center Santa Clara, California

2. Introduction • Interstitial lung disease (ILD) comprise of a diverse group of lung infiltrates that cause disruption of alveolar structures & have common clinical, radiographic & physiological consequences

3. Introduction • Interstitium of the lung refers to the space interposed between the basement membranes of the alveolar lining epithelium & capillary endothelium

4. Etiology • Over 100 causes of interstitial lung disease • 2/3 of causes have no know cause • Classified based on their clinical, radiographic & pathological features

5. Interstitium • Space contains connective tissue elements consisting of collagen, proteoglycans, glycoproteins, noncollagenous proteins, fibronectin & laminin • Interstitial macrophages, fibroblast & myofibroblast • Participate in lung repair • Can stimulate & contribute to scarring & injury

6. Interstitium • Anatomic boundaries of the interstitium include the alveolar epithelial lining cells & adjacent capillary network • Alveolar lumen is part of interstitium • Anatomy of interstitium can be altered by inflammatory cells, proliferation of fibroblast or disordered collagen deposits

7. Incidence • 100,000 hospital admissions a year • 15% of pulmonary practice • Incidence of ILD varies with disease entities • Scleroderma 100% • Rheumatoid arthritis 33% • Sarcoidosis 33% • Idiopathic pulmonary fibrosis 30-40%

8. Classification of Interstitial Lung Disease • Occupational/Environmental • Drugs & Poisons (chemo) • Connective Tissue Disease (SLE, RA…) • Idiopathic Interstitial Lung Disease • Infection (can give appearance of ILD) • Other Systemic Disease – i.e sarcoidosis

9. Occupational/Environmental • Silicosis • Asbestos • Coal workers’ pneumonconiosis • Berylliosis • Stannosis (tin) • Polyvinyl chloride pneumonitis • Humidifer Lung – hypersensitivity -

10. Drug Induced Interstitial Lung Disease • Nitrofurantoin - antibiotics • Amiodarone – cardiologist love this for Afib, aflutter, Vtac, Vfib and refractory rhythm (smurf drug) • Gold • Penicillamine • Dilantin • Bleomycin • Cytoxan • Radiation – breast cancer tx • Bromocryptine • Methotrexate

11. Connective Tissue Disease • Scleroderma • Systemic Lupus erythematosis – ILD in women • Rheumatoid Arthritis – ILD in men • Primary Sjogrens Syndrome • Mixed Connective Tissue Disease • Polymyositis-Dermatomyositis

12. Idiopathic Interstitial Pneumonias • Initially thought to be the same disease with different stages of idiopathic pulmonary fibrosis • Idiopathic Interstitial pneumonias have been recently reclassified into 4 categories • Usual Interstitial Pneumonia (UIP) • Nonspecific interstitial pneumonia (NSIP) • Desquamative interstitial pneumonia • Acute interstitial pneumonia

13. 5 Most Common Interstitial Lung Disease • Usual interstitial pneumonia • Nonspecific interstitial pneumonia • Collagen Vascular Disease • Hypersensitivity Pneumonitis • Sarcoidosis

14. Pathogenesis • Injury to the alveolar-capillary epithelial surface • Agents can reach the lung via airway or circulation • Not known whether genetics predispose individuals • Injury is severe or persistent healing will be inhibited

15. Pathogenesis • Initial step appears to be injury to lung cells by an unknown mechanism • Following injury, there is an influx of inflammatory & immune effector cells • Proliferation of type 2 epithelial cells • Attempt to restore integrity of epithelial surface • Synthesize a variety of matrix components & release complement & cytokines

16. Pathogenesis • Inflammatory cells are attracted to area & releasing proteolytic enzymes & oxygen free-radicals • Major requirement for injury is continued exposure to inciting agent • Persistence of inflammatory cells/immune effector cells eventually lead to loss of alveolar gas exchange units due to honey-combing & fibrosis • Genetic component

17. Pathogenesis

18. Clinical Presentation • History • Past, Occupational & Family History • Physical Examination

19. History • Typical patients are middle aged presenting with progressive dyspnea & nonproductive cough • Other symptoms are dependent on underlying process • Fever, weight loss, fatigue, myalgias & arthralgias

20. History • Most patients report chronic & progressive symptoms • Several diseases states have a more rapid presentation of symptoms (days-weeks) • Fever, leukocytosis & diffuse radiographic infiltrates suggest atypical pneumonia - days • BOOP, hypersensitivity pneumonitis, eosinophilic pneumonia, diffuse alveolar syndrome - weeks

21. Past, Occupational & Family History • Detailed & life-long occupational history must be obtained • Long latency period from time to exposure to disease • Environmental antigens & occupational exposure may lead to hypersensitivity pneumonitis

22. Past, Occupational & Family History • Heredity • Autosomal dominant form of IPF-Tuberous sclerosis & Neurofibromatosis • Autosomal recessive form of IPF-Gaucher’s Disease, Niemann-Pick & Hermansky-Pudlack syndrome

23. Past, Occupational & Family History • Sex • Lymphangioleiomyomatosis occurs only in premenopausal women – 100% exclusive • Interstitial lung disease of connective tissue disorders affect woman more often than males • Exception is Rheumatoid arthritis • Pneumoconiosises affect men more often – women don’t work as hard

24. Physical Examination • Characteristic finding is bibasilar rales • Clubbing of fingers are common in IPF • Rare in Sarcoidosis • Signs of pulmonary hypertension & cor pulmonale are generally seen only in advanced diseases

25. Diagnostic Test • Chest Radiography • High Resolution CT • Pulmonary Function Testing • Bronchoscopy/Bronchoalveolar Lavage • Lung Biopsy

26. Chest Radiography • CXR is useful in suggesting the presence but not the stage of ILD • 10% of CXR maybe normal in ILD • Most common radiographic pattern are reticular or a reticulonodular pattern • Honey-combing is a late finding • Pleural disease is uncommon in IPF • Suggestive of connective tissue disease • TQ in a women think of lymphangionmyelot….

28. High Resolution CT scan • Better resolution than conventional CT • Provide better resolution of pulmonary parenchyma & detects early interstitial lung disease • Patterns can strongly suggest presence of specific ILD • Direct biopsies

29. Pulmonary Function Testing • Can not distinguish an inflammatory stage from fibrosis or honey-combing • Classic findings are consistent with Restrictive Ventilatory Defect • Reduced vital capacity & total lung capacity

30. Pulmonary Function Testing • Uncommon to have an obstructive defectBronchiolitis obliterans or endobronchial sarcoidosis • Diffusion capacity is reduced due to loss of capillary bed • May precede abnormalities in lung volumes • ABG maybe normal or reveal hypoxemia due to ventilation & perfusion mismatch

31. Bronchoalveolar Lavage • Technique conducted by wedging bronchoscope into a subsegmental bronchus • Saline is instilled & aspirated for cytology & culture • Characterize the quantity of the inflammatory & immune effector cells • Lymphocytes-hypersensitivity pneumonitis & sarcoidosis • Neutrophils increased in IPF & asbestosis

32. Lung Biopsy • Provides a more accurate diagnosis • Exclude neoplastic & infectious process • Identify a more treatable process than originally suspected • Provide a better assessment of disease activity

33. Lung Biopsy • Biopsies should be large quantity of tissue from 2 sites in an area of involved & normal lung • Bronchoscopy • Video Assisted Thorascopy (VAT) • Decision to proceed with bronchoscopy or VAT depends on findings of HRCT

34. Lung Biopsy • Bronchoscopy maybe the initial procedure of choice • Good yield: • Sarcoidosis • Hypersensitivity pneumonitis • Eosinophilic pneumonia • Lymphangitic Carcinomatosis • Bronchoalveolar lavage can aid in diagnosing eosinophilic pneumonia, hypersensitivity pneumonitis, sarcoidosis & alveolar proteinosis

35. Lung Biopsy • VATS lung biopsy yields a specific diagnosis approximately 85% of cases • Useful in diagnosing UIP, Nonspecific interstitial pneumonia, desquamative interstitial pneumonia, eosinophic granuloma, • Can only performed once

36. Management of Interstitial Lung Disease

37. Management of Interstitial Lung Disease • Many of the ILDs are not responsive to therapy • Major goal of therapy • Identify & aggressively treat the inflammatory process • Removal of the offending agent • No accurate or specific method available to stage the intensity of the alveolitis in a serial fashion • Followed by HRCT & PFT

38. Treatment • Immunosuppressive agents • Azathioprine • Cytoxan • Cyclosporin • Corticosteroids

39. Corticosteroids • Mainstay of therapy for suppressing the alveolitis • IPF-40-50% may experience subjective improvement but only a 20% objective improvement • No evidence that steroids influence the natural course of ILD in the connective tissue diseases • Exception is polymyositis/dermatomyositis

40. Lung Transplantation • Indications for Referral • Failure to medical therapy • Worsening oxygen desaturation with minimal exercise • Resting hypoxemia • Worsening pulmonary function testing • Single Lung transplant has been standard procedure • Double Lung Transplant

42. Idiopathic Interstitial Pneumonias • Idiopathic Interstitial pneumonias are a subset of diffuse interstitial lung disease of unknown etiology • Initially thought to be the same disease with different stages • Recognized as 4 distinct diseases with different etiologies, rate of progression, prognosis & response to therapy

43. Idiopathic Interstitial Pneumonias • Idiopathic Interstitial pneumonias have been recently reclassified into 4 categories • Usual Interstitial Pneumonia (UIP) • Nonspecific interstitial pneumonia (NSIP) • Desquamative interstitial pneumonia • Acute interstitial pneumonia

44. Usual Interstitial Pneumonia (UIP) • Term is synonymous with IPF • Cause is unknown • Estimated prevalence of 14 to 42 per 100,000 • Men > Female • Mortality increased from 1992 to 2003 • 49.7 to 64.3 deaths per 1000 men • 42.3 to 58.4 deaths per 1000 women • Average survival is 3 years from time of diagnosis

45. Usual Interstitial Pneumonia (UIP) • Pulmonary function typically demonstrates a restrictive pattern & CXR reveals diffuse interstitial opacities associated with reduced lung volumes • HRCT demonstrates a peripheral & bibasilar reticulonodular opacities

46. Usual Interstitial Pneumonia (UIP) • Disease generally does not respond to prednisone alone –given but usually don’t respond • No therapy has proven to be effective • Current therapies include prednisone & azathioprin, cytoxan, mycophenolate (cellcept) • Lung transplant may improve survival in selected patients

47. Nonspecific Interstitial Pneumonia (NSIP) • NSIP maybe idiopathic or a manifestation of connective tissue-ILD, hypersensitivity pneumonitis, or drug reaction • 2 pathologic subtypes: cellular & fibrotic • Survival for cellular NSIP >10yrs • Survival for fibrotic NSIP is 5yrs

48. Nonspecific Interstitial Pneumonia • Cellular NSIP typically responds to prednisone • Therapy for fibrotic NSIP is same as cellular NSIP, but less clear

49. Desquamative Interstitial Pneumonia • Similar to Respiratory bronchiolitis interstitial lung disease (RBILD) • Smoking causes this disease • Typically resolves with smoking cessation • Some pts may require treatment with prednisone

50. Acute Interstitial Pneumonia • AIP presents with explosive onset of respiratory symptoms & characterized by rapid progressive respiratory failure associated with diffuse infiltrates • Similar to ARDS, differing only in that it is not preceded by catastrophic event • Pathology reveals diffuse alveolar damage • May respond to prednisone, however relapses are frequent • In hospital mortality is 33%