1. INTERSTITIAL LUNG DISEASE
SPEAKER-DR.SAGAR
DNB MED.RES

2. INTRODUCTION
ILDs represent a large number of conditions that involve the parenchyma of the lung—the alveoli, the alveolar epithelium, the capillary endothelium, and the spaces between these structures, as well as the perivascular and lymphatic tissues.
Also called Diffuse Parenchymal Lung Disease

3. INTRODUCTION
Heterogeneous group of disorders have similar clinical, roentgenographic, physiologic, or pathologic manifestations.
Often associated with considerable morbidity and mortality, and there is little consensus regarding the best management of most of them.

4. CLASSIFICATION
One useful approach to classification is to separate the ILDs 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 subdivided according to whether the cause is known or unknown.
For each ILD there may be an acute phase, and there is usually a chronic one as well. Rarely, some are recurrent, with intervals of subclinical disease.

5. Major Categories of Alveolar and Interstitial Inflammatory Lung Disease
ON LUNG RESPONSE-
Alveolitis, Interstitial Inflammation, and Fibrosis 
Granulomatous 

6. Alveolitis, Interstitial Inflammation, and Fibrosis
Known Cause-
Asbestos
Fumes, gases
Drugs (antibiotics, amiodarone, gold) and chemotherapy drugs
Radiation
Aspiration pneumonia
Residual of adult respiratory distress syndrome

7. UNKNOWN CAUSES Idiopathic interstitial pneumonias (IIP)-
 Idiopathic pulmonary fibrosis (usual interstitial pneumonia) (UIP)
 Desquamative interstitial pneumonia(DIP)
 Respiratory bronchiolitis-associated interstitial lung disease (RB-ILD)
 Acute interstitial pneumonia (diffuse alveolar damage)
 Cryptogenic organizing pneumonia (bronchiolitis obliterans with organizing pneumonia) (COD)
 Nonspecific interstitial pneumonia
Connective tissue diseases-
 Systemic lupus erythematosus, rheumatoid arthritis, ankylosing spondylitis, systemic sclerosis, Sjögren's syndrome, polymyositis-dermatomyositis
Pulmonary hemorrhage syndromes
 Goodpasture's syndrome, idiopathic pulmonary hemosiderosis, isolated pulmonary capillaritis

8. CONT… Pulmonary alveolar proteinosis
Lymphocytic infiltrative disorders (lymphocytic interstitial pneumonitis associated with connective tissue disease)
Eosinophilic pneumonias
Lymphangioleiomyomatosis (LAM)
Amyloidosis
Inherited diseases-
  Tuberous sclerosis, neurofibromatosis, Niemann-Pick disease, Gaucher's disease, Hermansky-Pudlak syndrome
Gastrointestinal or liver diseases -(Crohn's disease, primary biliary cirrhosis, chronic active hepatitis, ulcerative colitis)
Graft-vs.-host disease- (bone marrow transplantation; solid organ transplantation)

9. Granulomatous Known Cause-
Hypersensitivity pneumonitis (organic dusts)
Inorganic dusts: beryllium, silica

10. Unknown Cause(GRANULOMATOUS)
Sarcoidosis
Langerhans' cell granulomatosis (eosinophilic granuloma of the lung)
Granulomatous vasculitides--
 Wegener's granulomatosis, allergic granulomatosis of Churg-Strauss
Bronchocentric granulomatosis
Lymphomatoid granulomatosis

11. Incident Cases of ILD (Incidence of IPF=26-31 per 100,000) DILD=drug
Fibrosis=IPF
(Incidence of IPF=26-31 per 100,000)

13. What is the Pulmonary Interstitium?
Interstitial compartment is the portion of the lung sandwiched between the epithelial and endothelial basement membrane
Expansion of the interstitial compartment by inflammation with or without fibrosis
Necrosis
Hyperplasia
Collapse of basement membrane
Inflammatory cells

16. Clinical Assessment History Physical Exam Chest Imaging
Pulmonary Function Testing
At Rest
Exercise
Serologic Studies
Tissue examination

17. History: Age and Gender
FEMALES-
LAM
Tuberous sclerosis
MALES-
Pneumoconiosis

18. History: Medications www.pneumotox.com
Schwartz, ILD text book, 4th edition

19. History: Occupational and Environmental
INORGANIC

20. ORGANIC: Hypersensitivity Pneumonitis

21. Occupational ????

22. History: Duration of Illness
Acute Diseases (Days to weeks)
AIP, EP, Drugs, Hypersensitivity
________________________________________________________________________________________________________________
Subacute Diseases (weeks to months)
Sarcoid, Drug, COP
__________________________________________________________________________________________________________________
Chronic Diseases (months to years)
IPF, Pneumoconioses,LCH,Sarcoidosis

23. PRESENTATION
Dyspnea is a common and prominent complaint in patients with ILD.
Non-Productive Cough
Fatigue,Weight loss
Symptoms associated with other diseases
Clubbing ,cyanosis

24. EXAMINATION
Late inspiratory ‘Velcro’ crackles unaltered by coughing at lung bases are heard.
Features of RV failure
Loud P2 present.

25. Physical Findings Resting Tachypnea Shallow breathing Dry crackles
Digital clubbing
Pulmonary HTN
Non-pulmonary findings
In a normal finger, the length of the perpendicular dropped from point A to point B should be greater than a similar line from C to D. In clubbing, the relationships are reversed - that is, the distance C-D is greater than the distance A-B. The other important change is the angle described by A-C-E. In the normal finger this is usually <180 degrees whereas in clubbing it is >180 degrees. Redrawn from DeRemee, RA. Facets of the algorithmic synthesis. In: DeRemee, RA, (Ed), Clinical profiles of diffuse interstitial pulmonary disease, Mount Kisco, NY, Futura Publishing Company, Inc, 1990, pp

27. Localized thickening and tightness of the skin of the fingers or toes
Localized thickening and tightness of the skin of the fingers or toes. Sclerodactyly is commonly associated with atrophy of the underlying soft tissues.

29. Laboratory

30. ILD: Evaluation Radiographic Physiologic testing Lung Sampling CXR
HRCT
Physiologic testing
PFT
Exercise test
Lung Sampling
BAL
Lung biopsy: (TBBx, Surgical)

31. CXR CLUES Interstitial Infiltrates Nodular Linear or reticular Mixed
Honeycomb
Cysts and traction bronchiectasis
GGO
nodules, lines, honeycombing, and groundglass
opacification.

32. CXR CLUES Alveolar Filling Air-bronchograms Acinar rosettes
Diffuse consolidation
Nodule like, poor boarder definition
Silhouetting: obliteration of normal structures

33. Radiographic Patterns in ILD
Pleural Involvement
Adenopathy
Sarcoidosis
Lymphoma
Lymphangitic CA
Amyloidosis
Berylliosis
Silicosis
Kerley B lines
Lymphangitic Carcinomatosis
LAM
Drug Induced
Radiation Pneumonitis
Asbestosis
Effusion
Thickening
Plaques
Mesothelioma
Collagen vascular disease
Chronic LV failure
Lymphangitic CA
Lymphoma
LAM
Veno-occlusive disease
Acute Eosinophilic Pneumonia

34. IPF: CXR Reduced lung volume Basal and peripheral reticulation
Chest Radiograph in IPF
These chest radiographs show peripheral reticular opacities that predominate at the lung bases, but also involve the mid-lung zones. Lung volume is reduced.
Reduced lung volume
Basal and peripheral reticulation
Images courtesy of W. Richard Webb, MD.

35. CXR: LlMITATIONS CXR is normal:
in 10 to 15 % of symptomatic patients with proven infiltrative lung disease
30% of those with bronchiectasis
~ 60 % of patients with emphysema
CXR has a sensitivity of 80% and a specificity of 82% percent for detection of DPLD
CXR can provide a confident diagnosis in ~ 23 % of cases

36. A normal CXR does not rule out the presence of ILD

37. HRCT 2 essential technical factors: Does not use contrast
Narrow collimation
Use of a high spatial frequency reconstruction algorithm
Does not use contrast
Prone and supine
Inspiratory and expiratory

38. Characteristic HRCT findings
Bibasilar interstitial and intralobular reticular opacities
Interlobular septal thickening
Subpleural honeycomb changes
Traction bronchiectasis in the lower lobes.
There may also be a variable amount of ground-glass opacity.

39. HRCT
Conventional
Supine Prone

40. The terminal bronchiole in the center divides into respiratory bronchioles with acini that contain alveoli. Lymphatics and veins run within the interlobular septa
Centrilobular area in blue (left) and perilymphatic area in yellow (right)
It is the smallest lung unit that is surrounded by connective tissue septa. It measures about 1-2 cm and is made up of 5-15 pulmonary acini, that contain the alveoli for gas exchange. The secondary lobule is supplied by a small bronchiole (terminal bronchiole) in the center, that is parallelled by the centrilobular artery. Pulmonary veins and lymphatics run in the periphery of the lobule within the interlobular septa. Under normal conditions only a few of these very thin septa will be seen. There are two lymphatic systems: a central network, that runs along the bronchovascular bundle towards the centre of the lobule and a peripheral network, that is located within the interlobular septa and along the pleural linings.

41. HRCT Clues What is the dominant HR-pattern:
Reticular
Nodular
High attenuation (ground-glass, consolidation)
Low attenuation (emphysema, cystic)
Where is it located within the secondary lobule (centrilobular, perilymphatic or random)
Is there an upper versus lower zone?
Central versus peripheral predominance
Are there additional findings (pleural involvement, lymphadenopathy, traction bronchiectasis)

42. HRCT: Radiographic Pattern

43. HRCT Findings in Late IPF
Characteristic HRCT findings include bibasilar interstitial and intralobular reticular opacities, interlobular septal thickening, subpleural honeycomb changes, and traction bronchiectasis in the lower lobes, without pleural abnormalities. There may also be a variable amount of ground-glass opacity. However, extensive ground-glass opacity on CT of the lung (involvement of ≥30% of lung) should prompt consideration of another cause of IIF
This HRCT scan shows a reticular pattern with a predominantly subpleural distribution in a patient with mid- to late-stage IPF Septa[ thickening and honeycombing are also seen.
American Thoracic Society, European Respiratory Society. Idiopathic pulmonary fibrosis: diagnosis and treatment. International Consensus Statement. Am J Respir Crit Care Med. 2000;161:
Slide courtesy of Ganesh Raghu, MD.

44. Honeycomb lung

45. Classic IPF HRCT Basal and subpleural predominance Reticular opacities
HRCT near the lung bases shows subpleural reticulation with traction bronchiectasis. Subpleural honeycombing is also present. Honeycombing can be confidently diagnosed if air-filled cysts are visible in a subpleural location.
Reticular opacities
Traction
bronchiectasis
Honeycombing
Image courtesy of W. Richard Webb, MD.

46. Ground Glass Pattern HP
PCP pneumonia
DIP
NSIP
PAP
DAH
Fluid

47. Cysts or Cyst Like
Bronchiectasis
LAM EG E

48. PFT: Lung Volumes Restrictive Disease
TLC RV VC
Normal
ILD
NM Disease

49. DLCO AND ABG DLCO reduced but nonspecific.
Does not correlate with severity of disease
ABG-
Normal to severe hypoxemia
Retained CO2 rare ..in end stage disease

50. Fiberoptic Bronchoscopy and Bronchoalveolar Lavage (BAL)
In selected diseases (e.g., sarcoidosis, hypersensitivity pneumonitis, DAH syndrome, cancer, pulmonary alveolar proteinosis)
Useful in narrowing D/D
Usefulness of BAL in the clinical assessment and management remains to be established

51. Tissue and Cellular Examination
Most effective method in confirming diagnosis and assessment of disease
May identify a more treatable process than originally suspected
Avoids confusion and anxiety later in the clinical course if the patient does not respond to therapy or suffers serious side effects from it.

52. Biopsy Fiberoptic bronchoscopy initial procedure of choice.
If specific diagnosis not made.
Then VATS or Surgical biopsy can be done

53. Probability of Histologic Diagnosis of Diffuse Diseases
Transbronchial
Biopsy
Surgical
Biopsy
1. Granulomatous diseases
Often
2. Malignant tumors/lymphangitic
3. DAD (any cause)
4. Certain infections
5. Alveolar proteinosis
6. Eosinophilic pneumonia
7. Vasculitis
Sometimes
8. Amyloidosis
9. EG/HX/PLCH
10. LAM
Probability of Histologic Diagnosis of Diffuse Diseases
UIP is histologically identified by surgical lung biopsy (SLB). SLB is recommended if IPF is suspected, and particularly in cases with atypical clinical or radiologic features.
Transbronchial biopsy (TBBx) has limited value in making a definitive diagnosis of UIP. TBBx is most useful in identifying diseases that affect the central structures within the lung lobule, such as granulomatous diseases, malignant tumors, DAD, and the rest of the diseases listed as 16 in the table. It is sometimes useful if the diagnostic lesion is encompassed in the transbronchial biopsy, as in amyloidosis or vasculitis. However, TBBx is almost never a useful diagnostic tool for diseases such as UIP, even though features may be suggestive of UIP.
11. RB/RBILD/DIP
Never
12. UIP/NSIP/LIP COP
13. Small airways disease
14. PHT and PVOD
Courtesy of Kevin O. Leslie, MD.

54. Video Assisted Thoracic Surgery (VATS)
VATS is the preferred procedure for obtaining a lung biopsy
High diagnostic accuracy
Less morbidity and mortality than open lung biopsy
BAL and TBBx limited to excluding other IPF mimickers
Ideal biopsy
Two or more surgical wedge biopsies with areas of normal lung
Samples should measure 35 cm in length and 23 cm in depth
Outpatient thoracoscopic lung biopsy can be a safe and effective procedure for patients with interstitial or focal lung disease
Video Assisted Thoracic Surgery (VATS)
The surgical lung biopsy is often indicated to establish a diagnosis of UIP. Video Assisted Thoracic Surgery (VATS) is a less invasive alternative to open lung biopsy for obtaining sufficient tissue and has been shown to provide a high degree of diagnostic accuracy and safety. Videothoracoscopy reduces postoperative pain and pulmonary dysfunction and is often associated with no or lower mortality compared with open lung biopsy.
A recent study demonstrated that outpatient thoracoscopic lung biopsy was safe and effective in diagnosing patients with ILD. 72.5% of patients in the study were discharged within 8 hours of admission and 22.5% went home within 23 hours.
American Thoracic Society. Idiopathic pulmonary fibrosis: diagnosis and treatment. International Consensus Statement. Am J Respir Crit Care Med. 2000;161:
Chang AC, Yee J, Orringer MB, Iannettoni MD. Diagnostic thoracoscopic lung biopsy: an outpatient experience. Ann Thorac Surg ;
Rena O, Casadio C, Leo F, et al. Videothoracoscopic lung biopsy in the diagnosis of interstitial lung disease. Eur J Cardiothorac Surg. 1999;16:

55. Major goals of treatment
Permanent removal of the offending agent, when known
Early identification and aggressive suppression of the acute and chronic inflammatory process
thereby reducing further lung damage

56. Hypoxemia (PaO2 < 55 mmHg) at rest and/or with exercise should be managed by supplemental oxygen.
If cor pulmonale develops, diuretic therapy and phlebotomy may occasionally be required

57. TREATMENT Glucocorticoid therapy is recommended-
for symptomatic ILD patients with eosinophilic pneumonias, COP, CTD, sarcoidosis, 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.

58. GLUCOCORTICOIDS
A common starting dose is prednisone, 0.5–1 mg/kg in a once-daily oral dose for 4–12 weeks.
If the patient is stable or improved, the dose is tapered to 0.25–0.5 mg/kg for an additional 4– 12 weeks depending on the course.
Rapid tapering or a shortened course of glucocorticoid treatment can result in recurrence.
If the patient's condition continues to decline while on glucocorticoids, a second agent added and the prednisone dose is lowered to or maintained at 0.25 mg/kg per day.

59. Other agents
Cyclophosphamide and azathioprine (1–2 mg/kg lean body weight per day), with or without glucocorticoids in IPF, vasculitis, and other ILDs.
An objective response usually requires at least 8–12 weeks to occur
Other agents, including methotrexate, colchicine, penicillamine, and cyclosporine, have been tried.
However, their role in the treatment of ILDs remains to be determined

60. LUNG TRANSPLANTATION
Many cases of ILD are chronic and irreversible despite the therapy discussed above, and lung transplantation may then be considered

61. Idiopathic Pulmonary Fibrosis: Treatment
No therapy effective in the management of acute exacerbations of IPF
Often mechanical ventilation is required but is usually not successful, with a hospital mortality rate of up to three-fourths of the patients.
In those that survive, a recurrence of acute exacerbation is common and usually results in death at those times.

62. Nonspecific Interstitial Pneumonia (NSIP)
DIP
AIP
Idiopathic BOOP.

63. NSIP

64. TREATMENT OF NSIP Unlike patients with IPF (UIP),
Majority of patients with NSIP have a good prognosis (5-year mortality rate estimated at <15%) with most showing improvement after treatment with glucocorticoids, often used in combination with azathioprine

65. Acute Interstitial Pneumonia (AIP, Hamman-Rich Syndrome)
Fulminant form of lung injury -RARE
Diffuse alveolar damage on lung
ARDS like presentation.D/D Idiopathic ARDS
Pathologic confirmation of organizing diffuse alveolar damage
Treatment –supportive-Ventilation.
Steroids role controversial

66. Cryptogenic Organizing Pneumonia
Idiopathic BOOP
clinicopathologic syndrome of unknown etiology.
5-6th decade
Distinctive Xray-bilateral, patchy, or diffuse alveolar opacities in the presence of normal lung volume.
2/3rd pts recovery by Glucocorticoids

68. THANK YOU