Interstitial lung fibrosis diseases

DR.OLA FAROUK RAMMAH
Medical Specialist, Meeqat General Hospital.
Madinah,KSA

1. UPDATES IN INTERSTITIAL LUN G DISEASE DR\ OLA FAROUK RAMMAH Meeqat General Hospital,Madinah.KSA

2. DEFINITION Encompasses a group of disorders of diverse aetiologies with common features of varying degrees of fibrosis and inflammation of the lung parenchyma or interstitium. It includes over 200 different diseases which, in spite of their heterogenous nature have several common clinical, radiological and histological manifestations.

3. “INTERSTITIAL” – A MISNOMER The interstitium of the lung spans the region between the alveolar epithelial and capillary endothelial basement membranes. This region includes a variety of cell types (fibroblasts, myofibroblasts, and macrophages) and matrix components (collagens, elastin, and proteoglycans). al v eo l ar space proximal t o the Th e i n t e r s tit ium e x t ends f r o m the terminal and respiratory bronchioles. This group of pulmonary disorders frequently involves: alveolar epithelium, alveolar space, pulmonary microvasculature, respiratory bronchioles, larger airways & pleura

4.  ILDs have been difficult to classify because >200 known individual diseases are characterized by diffuse parenchymal lung involvement, either as the primary condition or as a significant part of a multiorgan process, as may occur in the connective tissue diseases (CTDs). ILDs classified into two groups based on the major underlying histopathology: those associated with predominant inflammation and fibrosis and those with a predominantly granulomatous reaction in interstitial or vascular areas Each of these groups can be further clinically subdivided according to known or unknown etiology

5. EPIDEMIOLOGY ILDs was considered to be rare in the past. Increased awareness & wider availability of HRCT and other diagnostic tests have led to increased recognition. ILDs constitute about 10% to 15% of the patients with respiratory diseases, seen at any large hospital in the country. About 50% of the ILDs are idiopathic in origin while others are associated with identifiable diseases, most commonly, a CTD. UIP, also known as IPF is the most common form of IIP.

6. PATHOGENESIS ILDs are non-malignant disorders and are not caused by identified infectious agents. The precise pathway(s) leading from injury to fibrosis is not known. Although there are multiple initiating agent(s) of injury, the immunopathogenic responses of lung tissue are limited, & the mechanisms of repair have common features The two major histopathologic patterns inflammation and fibrosis granulomatous

7. INFLAMMATION & FIBROSIS The initial insult is an injury to the epithelial surface causing inflammation in the air spaces and alveolar walls. If the disease becomes chronic, inflammation spreads to adjacent portions of the interstitium and vasculature and eventually causes interstitial fibrosis. Important histopathologic patterns found in the ILDs include UIP, NSIP, respiratory bronchiolitis, organizing pneumonia (BOOP), diffuse alveolar damage (acute or organizing), DIP, & lymphocytic interstitial pneumonia. The development of irreversible scarring (fibrosis) of alveolar walls, airways, or vasculature is the most feared outcome in all of these conditions because it is often progressive and leads to significant derangement of ventilatory function and gas exchange.

8. CELLULAR BASES FOR THE PATHOGENESIS

9. EPITHELIAL DAMAGE & ACTIVATION Multiple microinjuries damage and activate alveolar epithelial cells, which in turn induce an antifibrinolytic environment in the alveolar spaces, enhancing wound clot formation.

10. FIBROBLAST MIGRATION & PROLIFERATION Alveolar epithelial cells secrete growth factors and induce migration and proliferation of fibroblasts and differentiation into myofibroblasts

11. ANGIOGENISIS & MYOFIBROBLAST FOCI FORMATION Subepithelial myofibroblasts and alveolar epithelial cells produce gelatinases that may increase basement membrane disruption and allow fibroblast–myofibroblast migration. Angiogenic factors induce neovascularization.

12. FIBROSIS & IMPAIRED REEPITHELIAZATION Both intraalveolar and interstitial myofibroblasts secrete extracellular matrix proteins, mainly collagens. An imbalance between interstitial collagenases and tissue inhibitors of metalloproteinases provokes the progressive deposit of extracellular matrix. Myofibroblasts produces angiotensin II provoking alveolar epithelial cell death, further impairing reepithelialization.

13. GRANULOMATOUS LUNG DISEASE Characterized by an accumulation of T-lymphocytes, macrophages and epithelioid cells organized into discrete structures (granulomas) in the lung parenchyma. The granulomatous lesions can progress to fibrosis. Many patients with granulomatous lung disease remain free of severe impairment of lung function, or when symptomatic, they improve after treatment. DDx - sarcoidosis and hypersensitivity pneumonitis

14. DIAGNOSING ILD A clinical diagnosis is possible for many forms of ILD, especially if an occupational and environmental history is aggressively pursued. For other forms, tissue examination, usually, obtained by thoracoscopic lung biopsy, is critical to confirmation of the diagnosis. HRCT scanning improves diagnostic accuracy as experience with histologic-image correlation is perfected.

15. SIGNS & SYMPTOMS Dyspnoea is a common and prominent complaint in patients with ILD, especially the idiopathic interstitial pneumonias, hypersensitivity pneumonitis, COP, sarcoidosis & eosinophilic pneumonias. Some patients, especially patients with sarcoidosis, silicosis, hypersensitivity pneumonitis, lipoid pneumonia, or lymphangitis carcinomatosis, may have extensive parenchymal lung disease on chest x-ray without significant dyspnoea, especially early in the course of the illness. Wheezing is an uncommon manifestation of ILD but has been described in patients with chronic eosinophilic pneumonia, ChurgStrauss syndrome, respiratory bronchiolitis, and sarcoidosis.

16. Clinically significant chest pain is uncommon in most ILDs. However, substernal discomfort is common in sarcoidosis. S ac u u d t d e e c n he w s o t r p s a e in n , in m g a o y f in d d y i s c p at n e o a ea sp , e o s n p t e a c n i e a o ll u y s if p a n s e s u o m cia o t t e h d orax, tuberous sclerosis, LAM, and neurofibromatosis. F p r r a e n se k n h ti a n e g m m o a p n t i y fe s s is ta a ti n o d ns b o lo f o IL d D -s b tr u e t a c k a e n d b s e p s u e t e u n m in ar th e e ra D r A e H ly syndromes, LAM, tuberous sclerosis, and the granulomatous vasculitides. Fatigue and weight loss are common in all ILDs.

17. PHYSICAL EXAMINATION  The findings are usually not specific.  Most commonly, physical examination reveals tachypnoea and bibasilar end-inspiratory dry crackles, which are common in most forms of ILD associated with inflammation but are less likely to be heard in the granulomatous lung diseases. Crackles may be present in the absence of radiographic abnormalities on the chest radiograph. Scattered late inspiratory high-pitched rhonchi—so-called inspiratory squeaks—are heard in patients with bronchiolitis. The cardiac examination is usually normal except in the mid or late stages of the disease, when findings of pulmonary hypertension and cor-pulmonale may become evident. Cyanosis and clubbing of the digits occur in some patients with advanced disease.

18. INVESTIGATIONS Antinuclear antibodies and anti-immunoglobulin antibodies (rheumatoid factors) are identified in some patients, even in the absence of a defined CTD. An increased lactate dehydrogenase (LDH) level is a nonspecific finding common to ILDs. Elevation of the serum angiotensin-converting enzyme level is common in sarcoidosis. Serum precipitins confirm exposure when hypersensitivity pneumonitis is suspected, although they are not diagnostic of the process. Antineutrophil cytoplasmic or anti–basement membrane antibodies are useful if vasculitis is suspected.

19.  electrocardiogram is usually normal unless pulmonary hypertension is present; then it demonstrates right-axis deviation, right ventricular hypertrophy, or right atrial enlargement or hypertrophy.  Echocardiography also reveals right ventricular dilatation, hypertrophy, or both in the presence of pulmonary hypertension.

20. CHEST X-RAY  ILD may be first suspected based on an abnormal chest radiograph, which most commonly reveals a bibasilar reticular pattern. A nodular or mixed pattern of alveolar filling and increased reticular markings may also be present. A subgroup of ILDs—sarcoidosis, chronic hypersensitivity pneumonitis, silicosis, berylliosis, RA (necrobiotic nodular form), ankylosing spondylitis— exhibit nodular opacities with a predilection for the upper lung zones. The chest x-ray correlates poorly with the clinical or histopathologic stage of the disease. The radiographic finding of honeycombing correlates with pathologic findings of small cystic spaces and progressive fibrosis; when present, it portends a poor prognosis. In most cases, the chest radiograph is nonspecific and usually does not allow a specific diagnosis.

21. COMPUTED TOMOGRAPHY HRCT is superior to the plain chest x-ray for early detection and confirmation of suspected ILD. Coexisting disease (e.g., mediastinal adenopathy, carcinoma, or emphysema) is often best recognized on HRCT scanning. In the appropriate clinical setting, HRCT may be sufficiently characteristic to preclude the need for lung biopsy in patients with IPF, sarcoidosis, hypersensitivity pneumonitis, asbestosis, lymphangitic carcinoma, and PLCH. When a lung biopsy is required, HRCT scanning is useful for determining the most appropriate area from which biopsy samples should be taken.

22. PULMONARY FUNCTION TESTING Spirometry and Lung Volumes Measurement of lung function is important in assessing the extent of pulmonary involvement in patients with ILD. Most forms of ILD produce a restrictive defect with reduced total lung capacity (TLC), functional residual capacity, and residual volume. Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) are reduced, but these changes are related to the decreased TLC. The FEV1/FVC ratio is usually normal or increased. Lung volumes decrease as lung stiffness worsens with disease progression. A few disorders produce interstitial opacities on chest x-ray and obstructive airflow limitation on lung function testing (uncommon in sarcoidosis and hypersensitivity pneumonitis but common in tuberous sclerosis and LAM).

23. Arterial Blood Gas: The resting arterial blood gas may be normal or reveal hypoxemia (secondary to a mismatching of ventilation to perfusion) and respiratory alkalosis. A normal arterial O2 tension (or saturation by oximetry) at rest does not rule out significant hypoxemia during exercise or sleep. Carbon dioxide (CO2) retention is rare and is usually a manifestation of end-stage disease.

24. CARDIOPULMONARY EXERCISE TESTING : useful to perform exercise testing with measurement of arterial blood gases to detect abnormalities of gas exchange. Arterial oxygen desaturation, a failure to decrease dead space appropriately with exercise ratio, and an excessive increase in respiratory rate with a lower than expected recruitment of tidal volume provide useful information about physiologic abnormalities and extent of disease. Serial assessment of resting and exercise gas exchange is an excellent method for following disease activity and responsiveness to treatment Increasingly, the 6-min walk test is used to obtain a global evaluation of submaximal exercise capacity in patients with ILD. The walk distance and level of oxygen desaturation tend correlate with the patient’s baseline lung function and mirror the patient’s clinical course.

25. FIBEROPTIC BRONCHOSCOPY AND BRONCHOALVEOLAR LAVAGE (BAL)

26. TISSUE AND CELLULAR EXAMINATION Lung biopsy is the most effective method for confirming the diagnosis and assessing disease activity. The findings may identify a more treatable process than originally suspected, particularly chronic hypersensitivity pneumonitis, COP, respiratory bronchiolitis–associated ILD, or sarcoidosis. Biopsy should be obtained before the initiation of treatment. Fiberoptic bronchoscopy with multiple transbronchial lung biopsies (4-8 samples) is often the initial procedure of choice, especially when sarcoidosis, lymphangitic carcinomatosis, eosinophilic pneumonia, Goodpasture syndrome, or infection is suspected. If a specific diagnosis is not made by transbronchial biopsy, surgical lung biopsy by video-assisted thoracic surgery or open thoracotomy is indicated. Adequate-sized biopsies from multiple sites, usually from two lobes, should be obtained. Relative contraindications to lung biopsy include serious cardiovascular disease, honeycombing and other roentgenographic evidence of diffuse end- stage disease, severe pulmonary dysfunction, and other major operative risks, especially in the elderly.

27. MANAGEMENT OF ILD  Although the course of ILD is variable, progression is common and often insidious.  Because therapy does not reverse fibrosis, the major goals of treatment are 1) Permanent removal of the offending agent, when known 2) Early identification and aggressive suppression of the acute and chronic inflammatory process, reducing further lung damage. Supplemental oxygen for Hypoxemia. Treating underlying infections, cor-pulmonale. 5) Pulmonary rehabilitation to improve the quality of life in patients

28.  Glucocorticoids: First line therapy for suppression of the inflammation present in ILD, but the success rate is low. Glucocorticoid therapy is recommended for symptomatic ILD patients with eosinophilic pneumonias, COP, CTD, sarcoidosis, hypersensitivity pneumonitis, acute inorganic dust exposures, acute radiation pneumonitis, DAH, and drug-induced ILD. In organic dust disease, glucocorticoids are recommended for both the acute and chronic stages.

29. Starting dose is prednisone , 0.5–1 mg/kg OD oral This dose is continued for 4–12 weeks, at which time the patient is reevaluated. If the patient is stable or improved, the dose is tapered to 0.25–0.5 mg/kg and is maintained at this level for an additional 4–12 weeks, depending on the course. If the patient’s condition continues to decline on glucocorticoids, a second agent (Cyclophosphamide, azathioprine ) often is added and the prednisone dose is lowered to or maintained at 0.25 mg/kg OD.

30.  Cyclophosphamide, azathioprine (1–2 mg/kg lean body weight per day), and mycophenolate mofetil , with or without glucocorticoids, have been tried with variable success in IPF, vasculitis, progressive systemic sclerosis, and other ILDs. An objective response usually requires at least 8–12 weeks to occur. In situations in which these drugs have failed or could not be tolerated, other agents, including methotrexate and cyclosporine , have been tried. Many cases of ILD are chronic and irreversible despite the therapy, and lung transplantation may then be considered.

31. IDIOPATHIC PULMONARY FIBROSIS Also known as usual interstitial pneumonia(UIP) most common form of idiopathic interstitial pneumonia. IPF has a distinctly poor response to therapy and a bad prognosis. Type I pneumocytes are lost, and there is proliferation of alveolar type II cells. Clinical Manifestations: Exertional dyspnoea, Non-productive cough, and inspiratory crackles with or without digital clubbing may be present on physical examination.

32. IDIOPATHIC PULMONARY FIBROSIS HRCT lung scans typically show patchy, predominantly basilar, subpleural reticular opacities, often associated with traction bronchiectasis and honeycombing. A definite UIP pattern on HRCT is highly accurate for the presence of a UIP pattern on surgical lung biopsy. Atypical findings that should suggest an alternative diagnosis include extensive ground-glass abnormality, nodular opacities, upper or midzone predominance, and prominent hilar or mediastinal lymphadenopathy. Pulmonary function tests often reveal a restrictive pattern, a reduced DlCO, and arterial hypoxemia that is exaggerated or elicited by exercise.

33. Management of IPF: Untreated patients with IPF show continued progression of their disease and have a high mortality rate. There is no effective therapy for IPF. Thalidomide appears to improve cough in patients with IPF. Chronic microaspiration secondary to gastroesophageal reflux may play a role in the pathogenesis and natural history of IPF. Gastroesophageal reflux (GER) therapy may be of benefit in IPF. In patients with IPF, treatment with the three-drug regimen of prednisone, azathioprine, and N-acetylcysteine (NAC) or warfarin (in IPF patients who lacked other indications for anticoagulation) has been shown to increase the risks of hospitalization and death. Patients with IPF and coexisting emphysema (combined pulmonary fibrosis and emphysema [CPFE]) are more likely to require long-term oxygen therapy and develop pulmonary hypertension and may have a more dismal outcome than those without emphysema. Patients should be referred early for lung transplant because of the unpredictability of disease progression

34. Disease Age M:F C/F Imaging Prognosis REMARKS Nonspecific interstitial pneumo n itis 40-50 May be in d istingu i s ha b l e from UIP Bilateral, subpleural ground glass Prognosis good but depends on But Surgical Biopsy is (NSIP) opacities asso with lower lobe volume loss the extent of fibrosis at diagnosis greater than 10 years. needed to confirm. Cryptogenic organizing pneumo n itis (bronchioliti s obliterans organizing pneumonia [BOOP]) 50–60 Abrupt onset, frequently weeks to a few months following a flu- like illness. constitutional symptoms are common areas of air- space consolidation, ground-glass opacities, small nodular opacities, and bronchial wall thickening and dilation. Good Rule out infection and treat with steroids

35. Disease Age M:F C/F Imaging Prognosis REMARKS Respiratory br o nchi o l i ti s - associated interstitial lung disease younger Heavy smokers with similar com p l a ins Like UIP. Bronchial wall thickening, centrilobular nodules, ground glass opacity with Airtrapping Emphy s e m a tous change. survival greater than 10 y Spon tan e o us remission 20%. ILD with Obstructiv pattern Acute interstitial pneumonitis Ha mm a n- Rich syndrome. young Apparently normal in d istingu i s hable from that of idiopathic ARDS ARDS Diffuse b/l airspace consolidation with patchy symmetric areas of ground-glass attenuation POOR Most severe form of ILD Pneumonia

36. NONSPECIFIC INTERSTITIAL PNEUMONITIS (NSIP)

37. CRYPTOGENIC ORGANIZING PNEUMONITIS (BRONCHIOLITIS OBLITERANS ORGANIZING PNEUMONIA [BOOP])

38. Smoking related ILD Respiratory bronchiolitis- associated interstitial lung disease

39. ACUTE INTERSTITIAL PNEUMONITIS

40. OCCUPATIONAL & RECREATIONAL EXPOSURE RELATED ILD Exposure Associated Lung Disease Bird breeders and fanciers Hypersensitivity pneumonitis Automotive mechanics, Electricians Pipefitters Shipyard workers Asbestosis Electronic and computer industry workers Berylliosis Farmers Farmer’s lung (hypersensitivity pneumonitis) Hot tub, sauna, humidifiers Hypersensitivity pneumonitis Metal workers (tool and die) Metal-induced pneumoconioses Miners, Sandblasters, Ceramic workers Silicosis Miners (specifically coal) Coal workers’ pneumoconiosis

41. Coal miners pneumo c onioisis Rounded opacities between 1 and 5 mm (upper and middle zones) small irregular and linear opacities Progressive massive fibrosis almost always starts in an upper zone Calcification is not a feature Cavitation of PMF can occur Caplan's syndrome is the name given to the combination of rheumatoid disease and several round nodules (usually 1 to 5 cm in diameter) in the lungs of a coal miner.

42. SILI C OSIS Clues to diagnosis Micronodular pattern Simple silicosis : Upper lobes Small multiple nodules Egg shell calcification Complicated : >1 cm nodules Acute silicosis : small nodular pattern with ground glass appearance ( crazy paving ) PMF : nodules coalesce to large masses BAL : dust particles on polarised light

43. X Ray: reticular interstitial pattern pleural plaques ( lower lung field , cardiac border and diaphragm ) Irrregular linear opacities first noted in lower lung fields. HRCT : Distinct subpleural curvilinear opacities 5- 10 mm length parallel to pleural surface BAL: Asbestos bodies ASB E S T OSIS Clues to diagnosis

44. HYPERSENSITIVITY PNEUMONITIS Hypersensitivity pneumonitis (HP), or extrinsic allergic alveolitis, is a spectrum of interstitial, alveolar, and bronchiolar lung diseases resulting from immunologically induced inflammation in response to inhalation of a wide variety of different materials that are usually organic or low- molecular weight chemical antigens (or haptens) that may lead to irreversible lung damage. Despite the terms hypersensitivity and allergic, HP is not an atopic disease and is not associated with increased IgE or eosinophils.

45. Hypersensitivity pneumonitis (HP) has Acute, subacute & chronic manifestations. Acute manifestations include: transient fever, hypoxemia, myalgias, arthralgias, dyspnoea, and cough that occur 2 to 9 h after exposure and resolve in 12 to 72 h without specific treatment (sometimes longer after a particularly intense exposure). Patients exhibit tachypnea, bibasilar rales, and occasionally cyanosis. There is usually peripheral blood leukocytosis with neutrophilia and lymphopenia (without eosinophilia), and bronchoalveolar lavage (BAL) neutrophilia. Subacute or intermittent disease may result from repeated exposures, and manifest as productive cough, dyspnea, fatigue, and weight loss. There may be BAL lymphocytosis, frequently (although not always) with a predominance of CD8+ T lymphocytes.

46. Chronic HP is clinically more insidious, and patients may lack a history of acute episodes. present with a gradual onset of cough, dyspnea, fatigue, and weight loss. Symptoms are usually present for months to years. There is typically no fever, but tachypnea and bibasilar dry rales are usually present. This form of the disease may be difficult to distinguish from idiopathic pulmonary fibrosis. symptoms and signs of cor-pulmonale are not uncommon at presentation.

47. bilateral lower lobe 2- to 3-mm nodules diffuse nodular radiodensities in the lower lobes, with areas of ground- glass densities posteriorly.

48. INTERSTITIAL LUNG DISEASE IN CTD Suspect a CTD if patient has : Musculosketetal pain Weakness Fatigue Joint pains and swelling Photosensitivity Raynauds phenomenon Pleuritis Dry eyes or mouth

49. Progressive Systemic Sclerosis (PSS) Clinical evidence of ILD is present in about one-half of patients with progressive systemic sclerosis (PSS), and pathologic evidence is present in three-quarters. Pulmonary function tests show a restrictive pattern and impaired diffusing capacity, often before any clinical or radiographic evidence of lung disease appears. Pulmonary vascular disease alone or in association with pulmonary fibrosis, pleuritis, or recurrent aspiration pneumonitis is strikingly resistant to current modes of therapy.

50. Rheumatoid Arthritis ILD associated with RA is more common in men. Pulmonary manifestations of RA include pleurisy with or without effusion, ILD in up to 20% of cases, necrobiotic nodules (nonpneumoconiotic intrapulmonary rheumatoid nodules) with or without cavities, Caplan’s syndrome (rheumatoid pneumoconiosis), pulmonary hypertension secondary to rheumatoid pulmonary vasculitis, BOOP, and upper airway obstruction caused by cricoarytenoid arthritis.

51. Systemic Lupus Erythematosus Lung disease is a common complication in SLE. Pulmonary manifestations” Pleuritis with or without effusion is the most common. atelectasis, diaphragmatic dysfunction with loss of lung volumes, pulmonary vascular disease, pulmonary hemorrhage, uremic pulmonary edema, infectious pneumonia,and BOOP. Acute lupus pneumonitis characterized by pulmonary capillaritis leading to alveolar hemorrhage is uncommon. Chronic,progressive ILD is uncommon.It is important to exclude pulmonary infection. Although pleuropulmonary involvement may not be evident clinically, pulmonary function testing reveals abnormalities in many patients with SLE.

52. Polymyositis and Dermatomyositis ILD occurs in ∼ 10% of patients with polymyositis and dermatomyositis (PM/DM). Diffuse reticular or nodular opacities with or without an alveolar component occur radiographically, with a predilection for the lung bases. ILD occurs more commonly in the subgroup of patients with an anti–Jo-1 antibody that is directed to histidyl tRNA synthetase. Weakness of respiratory muscles contributing to aspiration pneumonia may be present. A rapidly progressive illness characterized by diffuse alveolar damage may cause respiratory failure.

53. HRCT in RA bibasilar peripheral reticular pattern, intralobular interstitial thickening distortion of the lung parenchyma Bilateral is present, predominantly on the left side bibasilar peripheral reticular pattern, pleural effusion thickening of the interlobular septa,

54. DRUG REACTIONS CAUSING ILD Alveolar Haemorrhage: Amiodarone, Amphotericin B, Clopidogrel, Cocaine, Cyclophosphamide, Haloperidol, Heparin, Hydralazine, Mitomycin, Nitrofurantoin, Penicillamine, Statins, Streptokinase, Sulfonamides BOOP (bronchiolitis obliterans organizing pneumonia ) Carbamazepine, Cephalexin, Chloroquine, Cocaine, Cyclophosphamide, interferon-a Mecamylamine Mesalamine Methotrexate,Nitrofurantoin, Phenytoin, Statins, Sulfasalazine Constrictive bronchiolitis Busulfan, penicillamine

55. EOSINOPHILIC PNEUMONIAS Classified as: simple eosinophilic pneumonia (Loeffler syndrome), acute eosinophilic pneumonia (AEP)-a process that clinically resembles ARDS, chronic eosinophilic pneumonia (CEP) that has a longer time course and does not result in respiratory failure.

56. AEP CEP

57. RADIATION PNEUMONITIS evident 6 weeks to 6 months following radiotherapy radiographs show alveolar opacities that generally conform to the treatment portals. In most cases, the pneumonitis is asymptomatic If symptomatic, characterized by the abrupt onset of fever, cough, and dyspnea. Managed with supportive care in conjunction with Glucocorticoids.

58. Vasculitic Disorders Lung Involvement ANCA Interstial Pattern seen Wegener granulomatosis Common c-ANCA >> p- ANCA 80–90% Diffuse Alveolar Hemorrage with nodules ,cavitation Microscopic polyangiitis Common Common p- ANCA > c-ANCA 80% DAH Churg-Strauss syndrome Common p-ANCA > c- ANCA 30–50% DAH with transient infiltates Goodpasture syndrome Common p-ANCA 10% DAH Takayasu arteritis Common Negative DAH ILD WITH A GRANULOMATOUS OR VASCULAR STRUCTURES

59. X ray : consolidation, typically resolving within a matter of days, multiple a b cess e s HRCT : ground-glass partial alveolar filling. Hb : anaemia ( iron defeciency ) BAL :- frank blood-staining in sequential lavage (acute presentation) and numerous macrophages containing iron, identified by Perl's stain Dlco :- may be increased in acute conditions but is chronically low ILD in VASCULITIC DISORDERS Suspect if Mononeuritis mutiplex Renal involvement Skin lesions haemoptysis

60. SARCOIDOSIS Probably one-third of sarcoid patients who come to medical attention are asymptomatic, and the disease is picked up as an incidental finding on chest imaging. Another one third have fever, malaise, and weight loss, and an equal proportion have shortness of breath (SOB), cough, and sometimes chest pain.  Pulmonary function varies by radiologic stage.  Low-stage disease patients may have normal pulmonary function, but airflow obstruction (because sarcoid granulomas can narrow the large and small airways and restriction are also seen.  High-stage (i.e., diffuse fibrotic) disease shows a restrictive pattern with decreased diffusing capacity; pulmonary hypertension may also be present.

61. Stage 0: No demonstrable radiographic abnormality • Stage 1: Hilar and mediastinal lymph node enlargement without radiographic parenchymal abnormality Stage 2: Hilar and mediastinal. lymph node enlargement plus parenchymal abnormality Stage 3: Parenchymal abnormality alone Stage 4: Advanced fibrosis.

62. SARCOIDOSIS CTD…. BAL :- lymphocytosis CD4 : CD8 > 3.5 is most specific PFT :- Restrictive pattern But Obstructive component present in many Biops y : - no n casea t in g g r anul o mas lymphocytosis Sr. ACE levels:- Hyper calciuria or Hypercalcemia

63. LYMPHOCYTIC INFILTRATIVE DISORDERS This group of disorders features lymphocyte and plasma cell infiltration of the lung parenchyma. Are benign or can behave as low-grade lymphomas. characterized by diffuse lymphadenopathy, fever, hepato- splenomegaly, and hemolytic anemia, with ILD in some cases. Lymphocytic Interstitial Pneumonitis Lymphomatoid Granulomatosis histologic findings : angiocentric malignant (T cell) lymphoma characterized by a poly- morphic lymphoid infiltrate, an angiitis, and granulomatosis.

64. PULMONARY ALVEOLAR PROTEINOSIS The clinical features of (PAP) are nonspecific  cough, shortness of breath (SOB), malaise, and sometimes chest pain or weight loss, usually developing in an indolent fashion. Chest examination is frequently unremarkable, although crackles, clubbing, and cyanosis are reported.

65. PULMONARY ALVEOLAR PROTEINOSIS diffuse reticulo-alveolar infiltrates BAT WING distribution BAL:- milky effulent foamy macrophages with lipoproteinous intraalveolar material thickened interlobular septa “crazy paving” ground glass fashion, sharply demarked from normal lung creating a “geographic” pattern.

66. PROGNOSIS Some forms of interstitial lung disease resolve completely, while others lead to long-term and irreversible scarring and lung damage with accompanying respiratory failure . Pulmonary hypertension can develop in cases of long- standing interstitial lung disease and can lead to cor pulmonale The prognosis is dependent upon the type and severity of interstitial lung disease as well as the underlying health status of the patient.

67. PREVENTION Avoid or limit exposure to toxins or treatments that can lead to ILD Proper diet and exercise reduces chance of developing ILD . Quitting smoking and avoiding exposure to substances known to cause ILD can prevent the disorder from developing or worsening. People who are employed in jobs where they may be heavily exposed to known causes of lung disease in the workplace typically should undergo routine screening for lung disease.