ILD, Nahid Ali Sherbini

1. APPROACH TO
INTERSTITIAL LUNG DISEASE
Dr Nahid Sherbini
Pulmonary Fellow

2. OBJECTIVES
• Review the spectrum of ILD or DPLD
• Identify clues on presentation to make the diagnosis
• Review common radiographic findings in ILD
• Role of BAL,TBBX and OLB in the diagnosis of ILD
• An algorithm to make the diagnosis

3. INTRODUCTION
• (ILDs) are a heterogeneous group of disorders
that are classified together because of similar
clinical, radiographic, physiologic, or pathologic
manifestations .

4. PULMONARY INTERSTITIUM
• Alveolar lining cells
(types 1 and 2)
• Thin elastin-rich
connective component
containing capillary
blood vessels

5. WHAT IS THE PULMONARY INTERSTITIUM?
• 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

6. • "interstitial" reflects the pathological abnormality begins
in the interstitium extensive alteration of alveolar and
airway architecture.

7. PATHOGENESIS
 The pathogenesis of ILDs is unknown.
 But more and more facts have shown that immune
cells and their cytokines play an important role in
the course of ILDs.

8. NOWADAYS THE MAJOR COURSES OF THE ILDS
INCLUDING:
• Intra-alveolar inflammation
• Immune cells and their cytokines injure epithelial and
endothelial cells
• Intra-alveolar fibrosis/alveolar collapse

9. In the course of ILDs many cytokines
involved in :
including TGF- , IGF- , prostaglandin E2,
platelet-derived growth factor, ects,.

10. CLASSIFICATION
• Divided into
-Associated with known causes and
-Idiopathic.
The treatment choices and prognosis vary among the different
causes and types of ILD

11. DPLD
Idiopathic Granulomatous
DPLD of known
Interstitial Lung Diseases Others
Cause
Pneumonias (Sarcoidosis)
LAM
Drugs Exposure CVD IPF IIP other than IPF Histiocytosis X
Malignancy
Respiratory
Desquamative
Hypersensitivity Bronchiolitis-
Pneumoconiosis Interstitial
Pneumonitis Interstitial Lung
Pneumonia
disease
IPF: 47-64%
Cryptogenic
Acute Interstitial Organizing NSIP: 14 to 36%
Toxic Inhalation Radiation
Pneumonia Pneumonia
RBILD/DIP: 10-
17%
Lymphocytic Non Specific COP: 4-12%
Interstitial Interstitial
Pneumonia Pneumonia
AIP: 2%
LIP: 2%

12. INCIDENT CASES OF ILD
Occupation
11% DILD
Sarcoidosis
5% DAH
8%
4%
CTD
9%
Other
11%
Pulmonary Fibrosis
52%
(Incidence of IPF=26-31 per 100,000)
Coultas AJRCCM ; 150:967

13. HISTORICAL CLASSIFICATION OF IIP
UIP/IPF
UIP UIP
DIP
RB-
ILD 2002
DIP ATS/ERS
NSIP
UIP-BO DIP-RBILD
LIP AIP
AIP
Giant cell IP
Cellular
NSIP
Fibrotic
1970 1997 COP
Liebow and Carington Katzenstein
Adapted from Ryu JH, et al. Mayo Clin Proc. 1998;73:1085-1101. LIP
Adapted from ATS/ERS. Am J Respir Crit Care Med. 2002;165:277-304.

15. CLINICAL ASSESSMENT
• History
• Physical Exam
• Chest Radiograph
• Pulmonary Function Testing
• Laboratory Studies
• Tissue examination

16. CLINICAL MANIFESTATIONS
• Progressive SOB
• Dry cough.
• Some patients may have OTHER e.g fatigue, weight loss, joint
pain.

17. HISTORY
• Age and gender
• Onset of symptoms
• Past medical history
• Smoking history
• Family history
• Prior medication use and irradiation
• Occupational and environmental exposures
• Symptoms

18. HISTORY: AGE AND GENDER
Age Gender
• LAM
• Tuberous sclerosis
• Pneumoconiosis

19. HISTORY
• Age and gender
• Duration of symptoms
• Past medical history
• Smoking history
• FH
• Prior medication use and irradiation
• Occupational and environmental exposures
• Symptoms

20. History: Duration of Illness
2. Acute Diseases (Days to weeks)
• DAD (AIP), EP, Vasculitis/DPH, Drug, CVD
________________________________________________________________________________________________________________
3. Subacute Diseases (weeks to months)
• HSP, Sarcoid, Cellular NSIP, Drug,
“Chronic” EP
__________________________________________________________________________________________________________________
4. Chronic Diseases (months to years)
• UIP, Fibrotic NSIP, Pneumoconioses,
CVD-related, Chronic HSP
Smoking (RBILD and PLCH)

21. MODIFIED LIEBOW CLASSIFICATION OF THE IDIOPATHIC
INTERSTITIAL PNEUMONIAS (KATZENSTEIN)
• Acute
• Acute interstitial pneumonia (AIP)
• Subacute
• Nonspecific interstitial pneumonia (NSIP)
• Lymphocytic Interstitial Pneumonia (LIP)
• Cryptogenic Organizing Pneumonia (COP)
• Desquamative interstitial pneumonia/ (DIP)
Respiratory bronchiolitis-associated
interstitial lung disease /(RBILD)
• Chronic
• Usual interstitial pneumonia (UIP)

22. HISTORY: SMOKING
• All of the following DPLD are • In Goodpasture’s syndrome
associated with smoking • 100% of smokers vs. 20% of
except: nonsmokers experience
a) IPF pulmonary hemorrhage
b) RBILD • Individuals exposed to asbestos
c) DIP who smoke are more likely to
develop asbestosis.
d) HP
e) Histiocytosis X

23. MEDICATIONS HISTORY

25. History: Occupational and
Environmental
INORGANIC

26. ORGANIC: Hypersensitivity Pneumonitis

27. WHAT IS THE OCCUPATION ?

28. PHYSICAL EXAMINATION
• Lung examination
• Cardiac examination
• Clubbing
• Extrapulmonary findings of systemic disease

29. PHYSICAL EXAMINATIONS
• Bilateral basilar, crepitant velcro-like rale
• wheezing, rhonchi and coarse rales are occasionally heard
• with advanced disease, patients may have tachypnea and
tachycardia
• At last, pulmonary hypertention and cor pulmonale may be
exist

30. PHYSICAL FINDINGS

36. LABORATORY TESTS
.

38. • Anti-JO-1 ab even in the absence of clinical myositis, as ILD
precedes the onset of myositis ~70% of patients with the anti-
synthetase syndrome.

39. SERUM MARKERS SUGGESTIVE OF ILD
• Surfactant protein A and B (SP-A, SP-B)
• Monocyte chemoattractant protein-1 (MCP-1)
• Kerbs von Lungren (KL)-6, a circulating, high-molecular weight
glycoprotein expressed by type II pneumocytes.

40. • In one report, evaluated in a mixed population of patients with
idiopathic ILD, collagen vascular disease-associated ILD, and
controls with and without pulmonary disease  KL-6 was
associated with the highest sensitivity, specificity and diagnostic
accuracy for the presence of ILD (94, 96, and 94 percent,
respectively).
• In the future, the KL-6 assay may help to identify and monitor ILD
in patients with RA and other CTD.
COMPARITIVE STUDYOF KL-6,SURFACTANT A ,B AJRCC 2002

41. ILD: EVALUATION
• Rdiographic
• CXR
• HRCT
• Physiologic testing
• PFT
• Exercise test
• Lung Sampling
• BAL
• Lung biopsy: (TBBx, Surgical)

42. CHEST RADIOGRAPHY
It is important method to diagnose the ILDs.

43. IMAGING -CXR
• The correlation between the radiographic pattern and the stage
of disease (clinical or histopathologic) is generally poor.
• Honeycombing correlates a poor prognosis.
• Review all previous chest films to assess the rate of change in
disease activity.

44. CXR: LMITATIONS
• 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 & HP
• CXR has a sensitivity and a specificity of ~80% for detection of DPLD
• CXR can provide a confident diagnosis in ~ 23 % of cases

45. A diffuse ground glass pattern early in the disease
Progresses, nodules, linear(reticular) infiltrates, or
a combination
 infiltrates become coarser and lung volume is
losthoneycomb pattern

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

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

53. CXR CLUES
Interstitial Infiltrates
• Nodular
• Linear or reticular
• Mixed
• Honeycomb
• Cysts and traction
bronchiectasis

54. IPF: CXR
Reduced lung volume Basal and peripheral reticulation
Images courtesy of W. Richard Webb, MD.

55. HRCT
• Both supine and prone images to avoid confusing dependent
atelectasis with interstitial opacities.
• HRCT provides greater diagnostic.
• Narrow the differential diagnosis of ILD.

56. Conventional HRCT
Supine Prone

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

58. nodular
linear

59. nodular
linear

60. honeycomb
ground glass pattern

61. CLASSIC IPF HRCT
Basal and subpleural predominance
Reticular opacities Traction Honeycombing
bronchiectasis
Image courtesy of W. Richard Webb, MD.

62. HRCT FINDINGS
• Bilateral symmetric hilar adenopathy and upper lung zone
reticular opacities  sarcoidosis
• Pleural plaques with linear calcification asbestosis.
• Centrilobular nodules that spare the subpleural region
hypersensitivity pneumonitis, sarcoidosis, Langerhans cell
histiocytosis &respiratory, follicular, and cellular bronchiolitis.

63. HRCT FINDINGS
• Irregular cysts associated with nodules in the upper and middle lung zones
pulmonary Langerhans cell histiocytosis.
• Subpleural and bibasilar reticular opacities associated with honeycomb changes and
traction bronchiectasis are IPF
Chronic hypersensitivity pneumonitis
ILD-associated with RA.
• In an asymptomatic patient, diffuse, calcified, nodular, interstitial opacities healed
varicella-zoster pneumonia.

64. DIP: RADIOGRAPHICS
• CXR:
• Normal: 3-22%
• Patchy GROUNG GLASS
• lower zone predilection
• HRCT:
• Ground glass opacities
• LL distribution (73 %)
• peripheral distribution (59%)

68. PREDOMINANT HRCT PATTERN?
Sjogren’s Syndrome
“NSIP”
WITH LIP

69. PERIPHERAL LOCATION
COP IPF

70. CHRONIC ALVEAOLAR INFITRATES
W (Wegner’s)
E (EP)
B (BOOP)
A (PAP, Aspiration)
L (Lymphoma)
L (Lipoid
Pneumonia)
S (Sacroidosis)

71. GROUND GLASS PATTERN
• HP
• PCP pneumonia
• DIP
• NSIP
• PAP
• DAH
• Fluid

72. CYSTS OR CYST LIKE
Bronchiectasis
LAM
EG
E

73. GALLIUM-67 LUNG SCANNING
• Gallium-67 lung scanning is of limited value as a means of
evaluating patients with ILD.

74. FDG-PET SCANNING
• The role of (18)F-2-deoxy-2-fluoro-D-glucose (FDG) (PET) in the evaluation
of ILD is unclear.
• Positive FDG uptake can be seen in
Sarcoidosis
Pulmonary Langerhans cell histiocytosis
Lymphangitic carcinomatosis
Not typically obtained in the evaluation of ILD.

75. CARDIAC EVALUATION
• ECG pulmonary HTN, OR cardiac disease.
• If heart failure BNP
• ECHO
• R HEART CATH WHEN NEEDED.

76. PFT
• TO
Severity
Obstructive, restrictive, or mixed

77. PFT
• A restrictive defect :
(TLC), (FRC), (RV) ,(FVC) and (FEV1)
but usually the changes are in proportion to the
decreased lung volumes

78. PFT: LUNG VOLUMES
RESTRICTIVE DISEASE
VC
VC
TLC VC
TLC TLC
RV RV
RV
Normal ILD NM Disease

79. AN INTERSTITIAL PATTERN ON CXR ACCOMPANIED BY
OBSTRUCTIVE AIRFLOW SUGGESTIVE OF :
1. Sarcoidosis
2. Lymphangioleiomyomatosis
3. Hypersensitivity pneumonitis
4. Pulmonary Langerhans cell histiocytosis
5. Tuberous sclerosis and pulmonary lymphangioleiomyomatosis
6. Combined COPD and ILD
7. Constrictive bronchiolitis

80. PFT
• A reduction (DLCO) is a common, but nonspecific finding
in ILD- , the severity of the DLCO reduction does not
correlate well with disease prognosis, unless the DLCO is
less than 35 % of predicted
• Due to effacement of the alveolar capillary units but more
importantly, to the extent of mismatching of V/Q of the
alveoli.

81. MODERATE TO SEVERE REDUCTION OF DLCO IN THE
PRESENCE OF NORMAL LUNG VOLUMES IN A PATIENT
WITH ILD SUGGESTS ONE OF THE FOLLOWING:
1. Combined emphysema and ILD
2. Combined ILD and PVD
3. PLCH
4. LAM
.

82. GAS EXCHANGE AT REST AND ON EXERTION
• Resting ABG may be normal in early ILD or
may reveal hypoxemia (secondary to V/Q mismatch)
CO2 retention is rare and usually a manifestation of end-stage
disease.

83. CARDIOPULMONARY EXERCISE TEST (CPET)
• Desaturation
• A failure to decrease dead space appropriately with exercise
• Increase in RR with a lower than expected recruitment of TV physiologic
abnormalities and the extent of disease.
• CPET is not necessary for every patient with ILD.
• a normal maximal CPET effectively excludes significant ILD .
• Serial assessment of resting and exercise gas exchange is one of the
methods used to follow ILD activity and responsiveness to treatment,
especially in (IPF).

84. 6MWT
• 6MWT have correlated with prognosis in several studies of IPF .
• Pulse oximetry desaturation to 88 during the 6MWT is
associated with a median survival of 3.21 y compared with a
median survival of 6.63 y in those who did not desaturate below
89%.

85. • The distance walked during the 6MWT is a reproducible
measure and correlates with the maximal oxygen
consumption (VO2max) obtained during a maximal
exercise test .

86. ROLE OF BRONCHOALVEOLAR LAVAGE
• The lavage fluid is sent for cell counts, cultures for mycobacterial,
viral and fungal pathogens, and cytologic analysis.
• Virtually all patients presenting with hemoptysis and radiographic
ILD should undergo BAL to confirm an alveolar source of
bleeding and identify any infectious etiologies.

91. • BAL is less likely to be helpful in patients with a radiographic
pattern suggestive of IPF.
• BAL does not have an established role in the assessment of
ILD progression or response to therapy

92. LUNG BIOPSY
• Obtained by flexible fiberoptic bronchoscopy, video-assisted
thoracoscopic (VATS) biopsy, or open lung biopsy.
• The histopathologic pattern found on the lung biopsy specimen
is evaluated in combination with the clinical information to
determine the diagnosis.

93. ROLE OF LUNG BIOPSY
1. Atypical or progressive symptoms and signs (age less than
50 years, fever, weight loss, hemoptysis, signs of vasculitis)
2. Atypical radiographic features
3. Unexplained extrapulmonary manifestations
4. Rapid clinical deterioration
5. Sudden change in radiographic appearance.

94. 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
Diagnosis obtained in 61/62 patients
72.5 % discharged home within 8 hours
22.5% discharged home within 23 hours
ATS/ERS Consensus Statement. Am J Respir Crit Care Med. 2000;161:646-664.
Chang AC, et al. Ann Thorac Surg. 2002.74;1942-1946.
Rena O, et al. Eur J Cardiothorac Surg. 1999;16:624-627.

101. PROBABILITY OF HISTOLOGIC DIAGNOSIS OF DIFFUSE DISEASES
Transbronchial Surgical
Biopsy Biopsy
1. Granulomatous diseases
2. Malignant tumors/lymphangitic
3. DAD (any cause)
4. Certain infections Often
5. Alveolar proteinosis
6. Eosinophilic pneumonia
7. Vasculitis
8. Amyloidosis
9. EG/HX/PLCH Sometimes
10. LAM
11. RB/RBILD/DIP
12. UIP/NSIP/LIP COP
13. Small airways disease Rare
14. PHT and PVOD
Courtesy of Kevin O. Leslie, MD.

102. KEY POINTS:
• Suspectinterstitial lung diseases with insidious dyspnea,
even with minimal or no radiographic findings
• A thorough history with exposures and systemic ROS is key
• Firm diagnosis for IPF requires ruling out treatable causes
and considering biopsy for atypical presentations

104. THANK YOU