3. By: Dr
Consultant Chest Physcian
TB TEAM Expert - WHO
Mansoura -Egypt
4. What is the Pulmonary Interstitium?
Interstitial compartment is the area of the lung between
the alveolar epithelial and capillary endothelial
basement membranes
5. Nomenclature
More than 200 diseases can result in Interstitial
Lung Disease (ILD).
The term interstitial is misleading since most of
these disorders are also associated with extensive
alterations of alveolar and airway architecture.
Diffuse parenchymal lung diseases (DPLD)
increasingly in favor worldwide as a generic term
for these disorders.
6. Epidemiology
o ILD is more frequent than previously recognized.
o Incidence ranges from 3 to 26 per 100.000 per year.
o The prevalence of preclinical and undiagnosed ILD
in the community is 10 times that of clinically
recognized.
o Among these, IPF is the most common, representing
at least 30% of the incident cases.
7. ILD presents a clinical conundrum as;
1st at least 150 clinical entities and situation are
associated with ILD.
2nd difficulty to determine the best specific
diagnostic approach.
3rd a conclusive cause cannot be ascertained
(even after lung biopsy) in a significant portion of
patients.
Finally even when a specific diagnosis is made, an
effective therapeutic regimen is not available for
many patients with ILD.
8. Table 1: Potential Causes /Categories
of Interstitial Lung Disease
Cause Categories
Byssinosis
Malt worker's lung
Coffee worker's lung
Bird fancier's lung
Farmer's lung
Bagassosis
Occupational or
other inhaled
organic agents
(EAA/HP)
Talc pneumoconiosis
Berylliosis
Hard metal fibrosis
Silicosis
Asbestosis
Coal worker's
pneumoconiosis
Occupational or
other inhaled
inorganic agents
Ankylosing spondylitis
Sjogrens syndrome
Bechet`s disease
Dermatopolymyositis
SLE
Rheumatoid arthritis
Scleroderma
Mixed CT disease
Collagen vascular
disease related
Chemotherapeutics ( Bleomycin, Methotrexate, Busulfan)
Drug induced Lupus (Phyenytoin, procainamide)
Antiarrhythmics (Amiodarone)
Antibiotics (Nitrofurantoin, sulfasalazine)
Gold
Drug related
9. Table 1: Potential Causes /Categories
of Interstitial Lung Disease
Cause Categories
Radiation / Radiotherapy Paraquat toxicity
Oxygen
Physical agents &
toxins
Tuberous sclerosis
Neurofibromatosis
Niemann-Pick disease
Sarcoidosis
Amyloidosis
Lymphangioleiomyomatosis
Primary disease
diagnosis
Pulmonary Langerhans cell histiocytosis
Bronchoalveolar carcinoma
Lymphangitis carcinomatosis
Neoplastic
diseases
Churg -Strauss syndrome
Wegener`s granulomatosis
Vasculitides
Pulmonary lymphoma
Chronic aspiration
Alveolar protienosis
Lipoid pneumonia
Eosinophilic pneumonia
Alveolar filling
diseases
Pulmonary edema
Pulmonary veno-occlusive disease
Disorders of
circulation
Tuberculosis
Residue of active infection of any type
Infection
10. Diffuse Parenchymal Lung Disease (DPLD)
DPLD of known cause,
eg, Drugs or
association, eg,
Collagen vascular
disease
Idiopathic
interstitial
pneumonias
Granulomatou
s DPLD, eg,
Sarcoidosis
,HP
Other forms
of DPLD, eg,
LAM, HX, etc
Idiopathic
pulmonary fibrosis
IIP other than idiopathic
pulmonary fibrosis
Desquamative
interstitial pneumonia
Acute interstitial
pneumonia
Nonspecific
interstitial pneumonia
Respiratory
bronchiolitis interstitial
lung disease
Cryptogenic
organizing
pneumonia
Lymphocytic
interstitial pneumonia
ATS/ERS Consensus Statement. Am J Respir Crit Care Med. 2002.
11. Diffuse Parenchymal Lung Disease (DPLD)
DPLD of known cause,
eg, Drugs or
association, eg,
Collagen vascular
disease
Idiopathic
interstitial
pneumonias
Granulomatou
s DPLD, eg,
Sarcoidosis
,HP
Other forms
of DPLD, eg,
LAM, HX, etc
Idiopathic
pulmonary fibrosis
IIP other than idiopathic
pulmonary fibrosis
Desquamative
interstitial pneumonia
Acute interstitial
pneumonia
Nonspecific
interstitial pneumonia
Respiratory
bronchiolitis interstitial
lung disease
Cryptogenic
organizing
pneumonia
Lymphocytic
interstitial pneumonia
ATS/ERS Consensus Statement. Am J Respir Crit Care Med. 2002.
12. Diffuse Parenchymal Lung Disease (DPLD)
DPLD of known cause,
eg, Drugs or
association, eg,
Collagen vascular
disease
Idiopathic
interstitial
pneumonias
Granulomatou
s DPLD, eg,
Sarcoidosis
,HP
Other forms
of DPLD, eg,
LAM, HX, etc
Idiopathic
pulmonary fibrosis
IIP other than idiopathic
pulmonary fibrosis
Desquamative
interstitial pneumonia
Acute interstitial
pneumonia
Nonspecific
interstitial pneumonia
Respiratory
bronchiolitis interstitial
lung disease
Cryptogenic
organizing
pneumonia
Lymphocytic
interstitial pneumonia
ATS/ERS Consensus Statement. Am J Respir Crit Care Med. 2002.
17. 2002
UIP
?
Fibrotic
NSIP
Prognostic Classification of ILD
? COP
Drug
reaction
Connective
tissue
disease
Cellular
NSIP
Hypersensitivity
Pneumonitis
Good Bad
18. Diagnostic Criteria for IPF in the
Absence of a Surgical Lung Biopsy
Major Criteria
Exclusion of other known causes of ILD
Evidence of restriction and/or impaired
gas exchange
HRCT: bibasilar reticular abnormalities
with minimal ground glass opacities
TBB or BAL that does not support an
alternative diagnosis
Minor Criteria
Age > 50 years
Insidious onset of otherwise
unexplained dyspnea on exertion
Duration of illness > 3 months
Bibasilar, inspiratory, Velcro®
crackles
All major criteria and at least 3 minor criteria must be present to
increase the likelihood of an IPF diagnosis
ATS/ERS. Am J Respir Crit Care Med. 2000;161:646-664.
19.
20. Approach to Diagnosing IPF
Clinical Evaluation: History, PE, CXR, PFTs,
6MWT
Not IIP Potential IIP
HRCT
Diagnostic of IPF or other
diffuse lung disease
Diagnosis uncertain
Surgical lung
biopsy
Transbronchial Bx or
BAL
Diagnostic Nondiagnostic
Not IPF IPF
Adapted from ATS/ERS Consensus Statement. Am J Respir Crit Care
Med. 2002.
21. Approach to the Diagnosis of
ILD
Clinical
• History
• Physical
• Laboratory
• PFTs
Primary care
physicians
Radiology
• Chest X-ray
• HRCT
Pathology
• Surgical lung biopsy
Pulmonologists Radiologists Pathologists
Multidimensional and multidisciplinary
22. Clinical Assessment
• History
• Physical Exam
• CXR - HRCT
• Pulmonary Function Testing
– At Rest
– Exercise
• Serologic Studies
• Tissue examination
24. History
1) Age
2) Gender
3) Smoking history
4) Medications
5) Duration of symptoms
6) Environmental
exposure
7) Occupational
exposure
8) Family history
25. HISTORY
1. AGE:
Some of the ILDs are more common in certain age
groups:
Age 20-40 years - Sarcoidosis
- CTD
- LAM
- EG
> 50years - Idiopathic pulmonary fibrosis
(cryptogenic fibrosing
alveolitis)
26. HISTORY
2. GENDER:
- Premenopausal female:
LAM (lymphangioleiomatosis)
- Female predominant:
ILD associated with CTD.
- Male predominant:
ILD associated with RA
Pneumoconiosis
27. HISTORY
3.SMOKING:
Diseases associated with smoker:
- EG (histocytosis X)
- Desquamative interstitial pneumonitis
- Respiratory broncholitis ILD
Diseases less likely to be seen in smoker:
- Hypersensditivity pneumonitis
-Sarcoidosis
28. History: Smoking
• All of the following
DPLD are associated
with smoking except:
a) IPF
b) RBILD
c) DIP
d) HP
e) Histiocytosis X
• In Goodpasture’s
syndrome
– 100% of smokers vs. 20%
of nonsmokers
experience pulmonary
hemorrhage
• Individuals exposed to
asbestos who smoke are
more likely to develop
asbestosis
31. HISTORY
5.DURATION:
i. Insidious over months or years (e.g. IPF,
Sarcoidosis)
ii. Acute (less than 3 weeks) (e.g. drug reaction,
acute hypersensitivity pneumonitis, chemical
exposure)
iii. Subacute: 3-12 weeks (e.g. BOOP)
32. History
6. OCCUPATIONAL HISTORY AND
ENVIROMENTAL EXPOSURES
• Each of the following requires specific exposure:
1. Pneumoconiosis
2. Hypersensitivity pneumonitis (HP)
• The occupational history should begin with the patient’s
first job and continues chronologically.
• The patient should be asked to describe the exact duties
at each job.
37. Physical examination of the respiratory
system is rarely helpful in the diagnostic
evaluation of interstitial lung diseases.
38. INTENSITY OF SYMPTOMS:
i. Minimal symptoms in the presence of grossly
abnormal chest radiograph (e.g., Sarcoidosis,
histocytosis X).
ii. Severe symptoms in the presence of mild
radiograph abnormalities (e.g., IPF, HP).
iii. Sudden worsening of dyspnea (particularly if
assocaites with pleural pain) may indicate a
spontaneous pneumothorax.
39. Diagnostic approach: Clinical picture
• Typically present with progressive exertional
dyspnoea and/or persistent nonproductive cough.
• Other unusual chest symptoms:
– Haemoptysis e.g. alveolar hemorrhage
syndromes, pulmonary vascular diseases
– Pleuritic chest pain e.g. collagen vascular
illness.
– Wheezing e.g. Churg -Strauss syndrome &
EAA.
• Dry bibasilar crepitations / Squeaks.
• Clubbing (most common in IPF)
• Cyanosis.
• Signs of right heart failure.
Late in advanced disease
40. • New onset of hemoptysis in a patient with known
ILD suggests a complicating malignancy.
• Fever: IPF, RA are almost never associated with
fever.
41. Diffuse crackles: presence or absence adds little.
May be present in the presence of normal c-xray.
“Velcro rales” are common in most forms of ILD.
They are less likely to be heared in sarcoidosis.
Inspiratory squeaks typical of Boop.
Clubbing: most commonly seen in IPF but non-specific.
Rare in EG, sarcoidosis, HP.
42. • Among patients with ILD clubbing is found in
25-50% of patients with IPF and 50% of
patients with DIP and 75% of patients with
ILD from rheumatoid arthritis.
43. Extra thoracic manifestations : directive but
not diagnostic.
i. Nasal discharge or other upper airway
symptoms that suggest Wegener’s
granulomatosis.
ii Arthritis: CVD, Sarcoidosis or granulomatous
vasculitides.
iii. IPF: arthralgias but never true synovitis.
iv. Skin rashes: common to Sarcoidosis, CVD
and granulomatous vasculitis.
48. Radiological Patterns of ILD
• Interstitial lung disease may result in four patterns
of abnormal opacity on chest radiographs and CT
scans:
1. Linear
2. Reticular
3. Nodular
4. Reticulonodular
• These patterns are more accurately and
specifically defined on (HRCT) scan - key
investigation
50. CHEST RADIOGRAPH
ILD is often suspected on the basis of an
abnormal chest x-ray.
Review all previous films to assess the rate of
change in disease activity.
Remember, chest radiograph is normal in 10%
of patients with ILD (particularly those with HP).
51. A normal CXR does not rule
out the presence of DPLD
52. – CXR is normal in 10 % of
ILD
- May be mistaken for heart
failure
54. Linear Pattern
•A linear pattern is seen when
there is thickening of the
interlobular septa, producing
Kerley lines.
•The interlobular septa contain
pulmonary veins and
lymphatics.
•The most common cause of
interlobular septal thickening,
producing Kerley A and B lines,
is pulmonary edema, as a
result of pulmonary venous
hypertension and distension of
Kerley B lines
Kerley A lines
55. DD of Kerly Lines
• Pulmonary edema is the most common cause
• Mitral stenosis
• Lymphangitic carcinomatosis
• Malignant lymphoma
• Congenital lymphangiectasia
• Idiopathic pulmonary fibrosis
• Pneumoconiosis
• Sarcoidosis
56. Reticular Pattern
• A classic reticular pattern is seen with Idiopathic
pulmonary fibrosis, in which multiple curvilinear
opacities form small cystic spaces along the
pleural margins and lung bases (honeycomb lung)
• Asbestosis
• Connective tissue disease
• Hypersensitivity pneumonitis
60. This 50-year-old man presented with end-stage lung fibrosis
PA chest radiograph shows medium to coarse reticular opacities
CT scan shows multiple small cysts (honeycombing) involving
predominantly the subpleural peripheral regions of lung.
Traction bronchiectasis, another sign of end-stage lung fibrosis.
61. IPF is a progressive disease. Successive computed tomography (CT) lung images show
reticular infiltrates with honeycombing in the basilar and peripheral portions of the lung.
The patient's disease was progressive and she died from respiratory failure at the age of
61.
62. Nodular pattern
A nodular pattern consists of multiple round opacities,
generally ranging in diameter from 1 mm to 1 cm
Nodular opacities may be described as miliary (1 to 2
mm, the size of millet seeds), small, medium, or large,
as the diameter of the opacities increases
A nodular pattern, especially with predominant
distribution, suggests a specific differential diagnosis
63. Nodular pattern in sarcoidosis. Posteroanterior chest radiograph shows
numerous bilateral nodules involving mainly the upper and middle lung zones.
Also note evidence of right paratracheal lymph node enlargement (arrow). The
patient was a 37-year-old woman with sarcoidosis.
64. Nodular Pattern. Innumerable tiny nodules are randomly scattered throughout
both lungs. Some of them also involve the fissures (arrowheads), however not
insistently. A few relatively spared areas with less nodules show reduced
vascularization [this was a miliary reactivation of an old tuberculosis (TB)].
68. Reticulonodular pattern
A reticulonodular pattern results from a combination of
reticular and nodular opacities.
This pattern is often difficult to distinguish from a purely
reticular or nodular pattern, and in such a case a
differential diagnosis should be developed based on the
predominant pattern.
If there is no predominant pattern, causes of both nodular
and reticular patterns should be considered.
71. A 71-year-old white man with rheumatoid arthritis (RA) and no pulmonary
complaints. A and B, Posteroanterior (PA) and lateral chest radiographs
demonstrate a bilateral reticulonodular pattern with a basal predominance
74. A single cut of the high-resolution computed tomography scan showing diffuse ground
glass and reticulonodular opacities, suggestive of interstitial pneumonitis.
81. Systemic sclerosis.
A: PA chest radiograph shows a bibasilar and subpleural distribution of fine
reticular ILD. The presence of a dilated esophagus (arrows) provides a clue
to the correct diagnosis.
B: CT scan shows peripheral ILD and a dilated esophagus (arrow).
83. Rule no. 3
A middle or upper lung predominant distribution
suggests: (Mycobacterium Settle Superiorly in Lung)
1. Mycobacterial or fungal disease
2. Silicosis
3. Sarcoidosis
4. Langerhans Cell Histiocytosis
84. Complicated silicosis. PA chest radiograph shows multiple
nodules involving the upper and middle lungs, with coalescence
of nodules in the left upper lobe resulting in early
85. Langerhan cell histiocytosis.
This 50-year-old man had a
30 pack-year history of
cigarette smoking.
A: PA chest radiograph
shows hyperinflation of the
lungs and fine bilateral
reticular ILD.
B: CT scan shows multiple
cysts (solid arrow) and
nodules (dashed arrow).
87. o The presence of cystic images within the parenchyma
raises the possibilities of three major cystic ILD
LAM, Tuberous sclerosis and Langerhans cell
granulomatosis
o In LAM and Tuberous sclerosis, the cysts are
numerous, thin walled, typically less than 2 mm in
diameter and distributed throughout the pulmonary
parenchyma.
o In Langerhans cell granulomatosis cysts are bizar
94. Lymphangitic carcinomatosis. This 53-year-old man presented with
chronic obstructive pulmonary disease and large-cell bronchogenic
carcinoma of the right lung.
CT scan shows unilateral nodular thickening (arrows) and a malignant
right pleural effusion.
96. Lymphangioleiomyomatosis
(LAM).
A: PA chest radiograph shows
a right basilar pneumothorax
and two right pleural drainage
catheters.
The lung volumes are
increased, which is
characteristic of LAM, and
there is diffuse reticular ILD.
B: CT scan shows bilateral
thin-walled cysts and a
loculated right pneumothorax
(P).
103. Helpful Radiographic Patterns in the Differential
Diagnosis of Interstitial Lung Disease
• Lung consolidation Lobar/Segmental
Infiltrates
Chronic or acute eosinophilic pneumonia
Bronchiolitis obliterans with organizing
pneumonia
Aspiration (lipid pneumonia)
Alveolar carcinoma
Lymphoma
Alveolar proteinosis
• Isolated lung cysts
Pulmonary histiocytosis X
Lymphangioleiomyomatosis
Chronic PCP
104. Helpful Radiographic Patterns in the Differential
Diagnosis of Interstitial Lung Disease
• Haze or ground glass attenuation
Hypersensitivity pneumonitis
Desquamative interstitial pneumonia
Respiratory bronchiolitis-ILD
Drug toxicity
Pulmonary hemorrhage
• In acute hypersensitivity pneumonitis HRCT show
multifocal diffuse ground glass attenuation despite a
normal chest radiograph.
• Smokers with symptomatic RBILD typically have patchy
ground glass attenuation on HRCT.
107. • HRCT scans are more sensitive and have a greater
ability to detect anatomic abnormalities than do
chest radiograph.
• It helps the surgeon to identify areas of non-fibrotic,
active disease and relatively unaffected areas to
guide appropriate site selection for biopsy.
108. • HRCT helps in identifying "active and reversible
inflammation" (ground glass attenuation) and
irreversible fibrotic manifestations (traction
bronchiectasis and honeycombing).
• Extensive fibrotic changes suggest end or
advanced stage disease with limited potential for
both invasive diagnostic and therapeutic
approaches which could be toxic.
109.
110. Pulmonary Function
Regardless of the cause, a restrictive lung defect
and decreased diffusing capacity (DLco) are the
predominant physiological abnormalities seen in
ILD.
Exercise affords the most sensitive diagnostic and
physiological test for ILD. The degree of arterial
hypoxemia induced by exercise and the alveolar-arterial
difference in P02 (PAO2 – PaO2 gradient)
correlate well with the degree of pulmonary fibrosis.
111. Pulmonary Function
• Usually a restrictive abnormality
– Normal FEV1/FVC ratio
– Reduced VC and TLC
– Impaired diffusing capacity
• Arterial hypoxemia at rest / exercise.
• Mixed PFT abnormality if DPLD is superimposed
on COPD
• Isolated abnormality in diffusion
– early interstitial pneumonia
112. Pulmonary Function
Most of the ILD have a restrictive defect.
Mixed pattern:
- Sarcoidosis
- Hypersensitivity Pneumonitis (HP)
- Histocytosis X
- Lymphangioleiomyomatosis (LAM)
- Wegener’s granulomatosis
- Broncholitis obliterans organizing pneumonia
(BOOP) rarely present with mixed pattern
113. Bronchoalveolar lavage (BAL)
• Narrow the differential diagnosis.
• Diagnostic: infectious causes, occupational
exposures, malignancy & pulmonary alveolar
proteinosis.
• Differential cell count of BAL:
– Sarcoidosis: lymphocytosis / ++ T-helper cells &
high CD4/CD8 ratio : > 2.
– HP: marked T lymphocytosis/ CD4: CD8 < 1.
– IPF: increases in neutrophils and eosinophils.
114. Bronchoalveolar lavage (BAL)
The value of differential cell count of BAL
in the diagnosis of DPLD has been
extensively explored & found to be less
helpful.
116. Transbronchial Lung Biopsy (TBX)
• Minimally invasive
• Performed at the same time as BAL.
• Useful in the diagnosis of some ILDs e.g. Sarcoidosis,
infection or
lymphangitis carcinomatosis .
Unfortunately, TBX is of limited
value in the diagnosis IIPs
small amount of tissue obtained.
117. Surgical lung biopsy
• Surgical lung biopsy remains the “gold standard” for
diagnosis.
• The size of specimens, site of biopsy, expertise of
pathologists are factors that may preclude a
conclusive diagnosis.
• The site of the biopsy should be chosen on the basis
of HRCT findings and ideally be at the interface of
involved and less involved lung tissue.
• A biopsy of more than one site in the lung is more
helpful.
118. Surgical lung biopsy
- Video-assisted Thoracoscopic (VATS) biopsy
-Open lung biopsy
VATS lung biopsy is the preferred method of obtaining
lung tissue.
Indication for biopsy
- Inflammatory cause
- Young patient (might require many years of
immunosuppression)
- Diagnosis nor clear
•If HRCT shows classical pattern of IPF, then biopsy is
not required
119. Probability of Histologic Diagnosis of DOLD
Surgical
Biopsy
1. Granulomatous diseases
2. Malignant tumors/lymphangitic
3. DAD (any cause)
4. Certain infections
5. Alveolar proteinosis
6. Eosinophilic pneumonia
7. Vasculitis
8. Amyloidosis
9. EG/HX/PLCH
10. LAM
11. RB/RBILD/DIP
12. UIP/NSIP/LIP COP
13. Small airways disease
14. PHT and PVOD
Transbronchial
Biopsy
Often
Sometimes
Never
Courtesy of Kevin O. Leslie, MD.
