1. 1 Restrictive and Interstitial Lung Disease J.B. Handler, M.D. Physician Assistant Program University of New England

2. 2 Abbreviations SLE- systemic lupus erythematosis DL CO - diffusing capacity for carbon monoxide HRCT- high resolution computed tomography ALS- Amyotrophic Lateral Sclerosis RR- respiratory rate IFIP- idiopathic fibrosing interstitial pneumonia RA- rheumatoid arthritis

3. 3 Restrictive Disease and Dysfunction Collection of diseases that are characterized by reduction in volume of air within the lung parenchyma. Abnormal reduction in pulmonary ventilation. Restrictive pattern on PFT’s. Compensated by RR. Multiple etiologies: Most common are forms of interstitial lung disease. Some diseases have both obstructive and restrictive components: Cystic fibrosis, others.

4. 4 Interstitial Lung Disease Heterogeneous group of diseases (>180) with common response to lung injury. Idiopathic fibrosing interstitial pneumonia (IFIP), formerly called Idiopathic (primary) Pulmonary Fibrosis: Classic example of restrictive lung disease. Multiple secondary etiologies- see below. Pathology is similar, regardless of etiology.

5. 5 Secondary Etiologies Drug related: Amiodarone (potent anti- arrhythmic), bleomycin (tx cancer), some antibiotics (sulfonamides), others. Occupational inhalation: Silica, asbestos, beryllium, others. Connective tissue disorders: SLE, Polymyositis, RA, scleroderma. Others: Radiation, amyloidosis, sarcoidosis. Infections: Fungal (Coccoidiomycosis, Pneumocystis), Mycobacterium, some viruses.

6. 6 IFIP Diagnosis of exclusion Must exclude other etiologies (via biopsy) before saying “idiopathic”. Variations of IFIP exist, with varying response to therapy. Characteristic clinical, radiographic, PFT and other findings. Poor prognosis as with many other etiologies of interstitial lung disease.

7. 7 Pathology Inflammatory infiltrate in lung parenchyma/interstitium: Inflammation of alveolar epithelium and capillary endothelium followed by: Fibrosis of the alveoli and interalveolar septum Inflammation can include the respiratory bronchioles. Thickening of alveolar-capillary membrane by collagen and fibrous tissue. Over timeFibrosis throughout lung parenchyma.

8. Terminal Respiratory Unit Images.google.com

9. 9 Pathology/Pathophysiology Inflammatory cellular and fibrotic response. Inflammatory cells release chemical mediators activation of fibroblasts collagen deposition. Tissue injury, vascular injury and permeability. Epithelial injury thickens/breaks alveolar- capillary membraneimpaired diffusion of gas (DL CO ).

10. 10 Pathophysiology Destruction of alveoli/capillariesV/Q mismatch; both shunting and increased dead space. Ongoing repair/re-injury cycle; non- homogeneous scarring throughout lung. Lung compliance.

11. Normal Lung Parenchyma Images.google.com

12. Pulmonary Fibrosis Images.google.com

13. 13 Clinical Presentation (IFIP) Insidious onset most often with gradual development of shortness of breath; initially exertional, then at rest. Other etiologies may have acutechronic presentation. History: Occupational exposure? Smoker? Travel history (parasitic infections) Risk factors for HIV

14. 14 Clinical Presentation Decreased activity tolerance Dry, non-productive cough +/- fever; depends on etiology Presentation may vary depending on etiology

15. 15 Physical Exam, Testing Lungs: Fine, inspiratory crackles (like velcro) at lung bases. RR late. Clubbing of fingers: bony growth and enlargement of terminal phalange; present 25-50% of cases. Chest x-ray (see below): May appear normal until advanced disease. HRCT- may be useful- confirms “honey- comb pattern”.

16. Clubbing of Fingers Images.google.com

17. Chest X-Ray Lung volume Interstitial “honeycombing” Indicates advanced Disease Images.google.com

18. 18 PFT’s and ABG Marked reduction in all lung volumes. FVC, FEV 1, both often markedly Normal FEV 1 /FVC (or ) DL CO ABG: progressive hypoxemia due to both DL CO and V/Q mismatch. Worse with exercise. PCO 2 reflects increased respiratory rate to accommodate hypoxemia. PCO 2 levels rare except with end stage disease.

19. 19 Lung Biopsy Most important tool to confirm diagnosis and sort out underlying etiologies. Trans bronchial biopsy- least invasive, but sample size to small in most cases. Thoracoscopic biopsy- less invasive than open thoracotomy but still requires small incisions into thorax. Open lung biopsy- requires thoracotomy; multiple samples obtained from different areas of lung.

20. 20 Treatment No data to show that any treatment improves survival or quality of life of in patients with IFIP. Progressive disease in most patientsdeath in 3-5 years. Other etiologies sometimes respond to systemic corticosteroids (prednisone, et al) or immunosuppressive agents with varying degrees of improvement.

21. 21 Restrictive Disease: Others Neuromuscular diseases: ALS, Muscular Dystrophy, Polio,etc. Impair lung inflation; restrictive pattern on PFT’s. Kyphoscoliosis: Decrease lung volume; restrictive pattern on PFT’s. – abnl forward bending puts pressure on lungs Pleural diseases: prevent lung expansion; restrictive pattern on PFT’s.

22. Scoliosis Images.google.com