1. Interstitial Lung Diseases Sevda Özdoğan MD, Prof. Chest Diseases

2. Definition  Interstitial lung diseases covers a group of diffuse lung disorders that involve infiltration of alveolar air spaces or thickening of pulmonary interstitial structures  This heterogenious group of diseases have similar clinical, radiological and physiological characteristics

3. Classification Alveolar proteinosis, microlithiasis Berilliosis, hypersensitivity pn, histiocytosis Occupational radiation 40-50%

5. pneumoconiosis

6. Hypersensitivity pneumonitis

7. Collagen tissue diseases associated with ILD  SLE  RA  PSS  Sjögren sydrome  Polymyositis-dermatomyositis  Mixed connective tissue disease  Ankylosing spondylitis

8. Other Systemic Diseases  Sarcoidosis  Vasculites (Wegener, Churg Strauss)  Hemorragic Syndromes (Goodpasture, Idiopathic pulmonary hemosiderosis)  Hystiositosis X  Chronic Gastric aspiration  Lymphangitis Carcinomatosa  Chronic pulmonary edema  Chronic uremia  Alveolary proteinosis

9. Epidemiology  The known insidance and prevalance rate of ILD depens on some reports which may not represent the population  Estimated prevalance in man is 80.9/100 000 population  Estimated prevalance in woman is 67.2/100 000 population

10. SYMPTOMS  Dyspnea: Progressive, prominent in exercise. Sudden worsening of dyspnea, particularly if associated with pleural pain, may indicate a spontaneous pneumothorax.  Cough: A dry cough

11.  Hemoptysis: Diffuse alveolar hemorrhage syndromes, Vasculitides  Churg strauss, Wegener Granulomatosis  Behçet’s disease Can be due to other complications  Lung cancer  Pulmonary tuberculosis  Symptoms of Right Hearth Failure

12. HISTORY  The cause of the illness is often recognized from the patient's history.  Entire lifelong employment  Prior medication use  Symptoms of a systemic disease Musculoskeletal pain, weakness, fatigue, fever, joint pains or swelling, photosensitivity, dry mouth or eye

13. Gender:  Female Lymphangioleiomyoma tosis (Premenopausal) pulmonary involvement in tuberous sclerosis Connective tissue diseases  Male ILD associated with rheumatoid arthritis occupational exposures, pneumoconiosis.

14. Smoking history  Current or former smokers Hystiocytosis X DIP, IPF, RBILD  Never or exsmokers Sarcoidosis Hypersensitivity pneumonitis.  Active smoking can lead to complications in Goodpasture's syndrome, in which pulmonary hemorrhage is far more frequent in current smokers.

15. Family history Tuberous sclerosis, Neurofibromatosis  Idiopathic pulmonary fibrosis,  Sarcoidosis

16. PHYSICAL EXAMINATION  Physical examination is usually nonspecific  Crackles or "velcro rales" are common in most forms of ILD, although they are less likely to be heard in the granulomatous lung diseases, especially sarcoidosis.  Scattered late inspiratory high-pitched rhonchi (inspiratory squeaks) are frequently heard on chest examination in patients with bronchiolitis.

17.  Cyanosis  Tachypnea  Tachicardia  Cor pulmonale (edema, hepatomegali)  Extrapulmonary manifestations of systemic diseases Erythema nodosum (sarcoidosis, tb) Telenjiectasis (scleroderma) Joint deformities (RA)

18.  Clubbing: Common in IPF, Asbestosis

19. Diagnosis  History  Chest radiography Chest x-ray (can be normal in 10%) HRCT  The routine laboratory evaluation is not much helpfull but should be done (biochemical and hematologic tests)

20. Chest x-ray  All available previous chest radiograms should be reviewed to ascertain the onset, progression, chronicity and stability of the disease Diffuse alveolar (aciner) pattern, lineer, nodular or reticulonodular infiltrations Cystic changes (honeycombing) can be present

21. 5-10 mm nodules aciner pattern Cystic changes (Honeycombing)

23. Reticular pattern Normal

24.  The distribution of the lesions (Upper or lover zone distribution) can be usefull in narroving the differential diagnosis  The presence and the pattern of adenopathy may provide additional clues

25. HRCT  More sensitive and specific than chest radiographs Graund grass attenuation Lung consolidation Reticular opacities Nodules Cysts Fibrotic changes  Honey combing

27. Pulmonary Function Testing  A restrictive defect with reductions in total lung capacity (TLC), functional residual capacity (FRC), and residual volume (RV)  Flow rates are decreased (FEV1 and FVC), but the changes are in proportion to the decreased lung volumes; thus, the FEV1/FVC ratio is usually normal or increased  A reduction in the DLCO is a commonly found

28. Arterial Blood Gas analysis  The resting arterial blood gases may be normal or may reveal hypoxemia  A normal resting PaO2 does not rule out significant hypoxemia during exercise or sleep, which is common in ILD.  Carbon dioxide retention is rare and usually a manifestation of end-stage disease.

29. Invasive Diagnostic techniques  FOB Bronchoalveolar lavage (BAL) Transbronchial lung biopsy  VATS

30. Treatment  Avoid the exposed etiologic factor if there is any  Supportive care (Oxygen, pulmonary rehabilitation)  Treat the underlying disease if there is any  Corticosteroids  Immunesuppressive treatment  Lung transplantation

31. Sarcoidosis Sarcoidosis is a multisystem granulomatous disorder of unknown cause(s). It commonly affects young and middle-aged adults and frequently presents with bilateral hilar lymph- adenopathy, pulmonary infiltration, ocular and skin lesions. VII İnternational Sarcoidosis Meeting 1976

32.  The histologic hallmark is noncaseating granulomas

33. Etiology  The cause of Sarcoidosis remains unknown  Despite the lack of specific infectious cause Tuberculosis Atipic mycobacteria Epstein Barr virus Fungal infections Mycoplasma are investigated

34. Organ involvement in sarcoidosis Organ % of patients Mediastinal lymph nodes 95-98% Lungs>90% Liver50-80% Spleen40-80% Eyes20-50% Peripheral lymph nodes 30% Skin25% Nervous system 10% Heart (clinically) 5%

35. Chest x-ray Bilateral hiler adenopathy Bilateral hiler adenopathy+ paranchymal infiltrates

36. Chest radiographic stages of sarcoidosis StageFrequency 0Normal5-10% IBHL50% II BHL and parenchymal infiltrates 25% III Parenchymal infiltrates without BHL 15% IV Signs of fibrosis 5-10%

38. HRCT  Hilar and mediastinal lymphadenopathy  Beaded or irregular thickening of the bronchovascular bundles  Nodules along bronchi, vessels, and subpleural regions  Ground glass opacification  Parenchymal masses or consolidation  Parenchymal bands  Cysts  Traction bronchiectasis  Fibrosis with distortion of the lung architecture

39. Clinical Symptoms  2/3 of the patients are asymtomatic diagnosed in an incidental chest radiogram  Respiratory symptoms Dyspnea (marked on exertion) Cough (nonproductive) Chest discomfort (Chest pain often difficult to describe) Chest tightness and Wheesing (In chronic fibrocystic sarcoidosis)

40. Systemic / constitutional symptoms  Fatigue (up to 70% of patients)  Fever (usually low-grade, but up to 40°C possible)  Weight loss (2-6 kg during 10-12 weeks)  Symptoms of involved system

41. Löfgren’s Syndrome  It is a well defined presentation of sarcoidosis that consists of Erythema nodosum Polyartritis Bilateral hiler lymphadenopathy  The unset is usually abrupt  In most cases spontaneous remission occurs

42. Heerfordt’s Syndrome  Also known as Uveoparotid fever Consists of Fever Anterior uveitis Parotid and lacrimal gland enlargement Bilateral hiler adenopathy Facial paralysis  Has an abrupt unset

43. Diagnostic Evaluation  History (occupational and environmental exposure, symptoms)  Physical examination  Postero-anterior chest radiogaphy  Pulmonary function tests: spirometry and CO diffusion capacity  Serum chemistries: calcium, liver enzymes, creatinine, blood urea nitrogen, ACE  Urine analysis  Electrocardiography  Routine opthalmologic examination  Tuberculin skin test  Tissue biopsy

44. Bronchoscopic evaluation  FOB can be usefull in tissue sampling by Bronchial mucosal biopsy (there may be nodularity, mucosal edema, hypervascularity) Transbronchial needle aspiration of the mediastinal lymph nodes Transbronchial lung biopsy  BAL sampling Increased lymphocyts to 20-50% (<10% in normal subjects)

45.  The easiest accessible biopsy site should be preferred for tissue sampling A sklin nodule Superficial lymph node Nasal mucosa, salivary gland  Mediastinoscopy  VATS or thoracotomy rarely needed

46. Treatment  >80% of the patients undergo spontaneous remission depending on the stage of the disease with the highest rate in the early stages  Which patients should be treated??

47. Treatment indications  Systemic symptoms (Fever, weight loss)  Progressive symptomatic pulmonary involvement (Dyspnea, cough, hypoxemia)  Multipl vital organ involvement  Myocardial involvement  Eye involvement that is resistant to topical treatment  Santral Nervous system involvement  Hypercalcemia

48.  Corticosteroids minimum of 8-12 months  Supportive management of patients who have advanced disease and corpulmonale  Special topical treatments for extrapulmonary disease