Interstitial lung diseases (ILDs) encompass a variety of conditions affecting lung parenchyma, classified primarily based on pathogenesis, with over 200 known individual diseases. Diagnosis involves a comprehensive clinical evaluation, radiography, and often lung biopsy, while treatment focuses on managing symptoms, addressing underlying causes, and preventing progression. Key evaluations include pulmonary function tests to assess lung capacity and diffusion capacity, with management strategies tailored to individual disease variants.

1. INTERSTITIAL
LUNG DISEASES
Prepared by -Mikru Taye C1- student-2019 GC
Moderator–Dr. Getachew Endrie (MD, Internist)
10/2/2019
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2. Presentation out line
 Introduction
 Classification
 Pathogenesis
 Clinical evaluation /presentation
 Diagnosis
 Treatment
 Follow up
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3. 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 those structures—as well as the
perivascular and lymphatic tissues.
 The disorders in this heterogeneous group are
classified together because of similar clinical,
physiologic, radiologic or pathologic manifestations.
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4. Introduction
 There are more than 200 known individual diseases
 Classification
1. Those associated with predominant inflammation
and fibrosis
2. Those with a predominantly granulomatous reaction
in interstitial or vascular areas
 Each of these groups can be subdivided further
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.
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6. Introduction
 The most common ILDs of unknown etiology are
Sarcoidosis
IPF and
Pulmonary fibrosis associated with connective tissue
diseases.
 The most common ILDs of known etiology are those of
environmental and occupational related ILDs
 especially the inhalation of
inorganic dusts
organic dusts
various fumes or gases
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9. Pathogenesis
 The ILDs are nonmalignant 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, and the mechanisms of repair have common
features
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10. Pathogenesis
 Granulomatous Lung Disease
 It is characterized by an accumulation of
➢ T lymphocytes,
➢ macrophages, and granulomasin-> in the lung
➢ epithelioid cells
 Many patients with granulomatous lung disease
remain free of severe impairment of lung function
or, when symptomatic, improve after treatment
 Main DDx: Sarcoidosis and hypersensitivity
pneumonitis
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11. ✓ Pathogenesis
 Inflammation and Fibrosis
 Initial Insult: an injury to the epithelial surface that
causes 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 in these ILDs:
✓ usual interstitial pneumonia (UIP),
✓ nonspecific interstitial pneumonia,
✓ respiratory bronchiolitis
✓ diffuse alveolar damage (acute or organizing), and
✓ lymphocytic interstitial pneumonia 10/2/2019
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14. Clinical Evaluation
 A thorough and comprehensive history may provide
invaluable information that can suggest certain entities
and provide suspicion that a patient may have a specific
diagnosis such as hypersensitivity pneumonitis (HP) or
CTD-ILD
 Additional clues to an ultimate diagnosis can be provided
by pulmonary and extra-pulmonary physical examination
findings,
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15. Clinical Evaluation
 The differential diagnosis can be considerably narrowed
when key elements of the patient interview and physical
examination findings are combined with appropriate
measurements of lung function, specific blood tests such
as autoimmune serologies to assist in the detection of
CTD if such are indicated, extra-pulmonary tissue
sampling (e.g. lymph node or skin biopsy), and thoracic
imaging.
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16. Clinical Evaluation
 History
 Progressive exertional dyspnea is the commonest
complaint.
 Some may not have dyspnea – eg Sarcoidosis
 The other is persistent non productive cough
 Chest Pain, Hemoptysis and Wheeze are uncommon
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17. Diagnosis
 History
 Pattern->Acute, Subacute , Chronic and/or Episodic.
 Age-> 20-40 years ,IPF older than 60yrs.
 Sex-> Mostly female.
◼ In males -> ILDs in Rheumatoid Arthritis, IPF and
Occupation related ILDs like pneumoconiosis
 Some ILDs are related with smoking.
◼ Two third to 75% of IPF and familial lung fibrosis
have history of smoking cigarette.
◼ A strict Occupational and Environmental History
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20.  P/E
 The
findings are
usually not
specific
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23. Diagnosis
 Radiography
 CXR findings include
◼ a bibasilar reticular pattern
◼ A nodular or mixed pattern of alveolar filling and
increased reticular markings
◼ A subgroup of ILDs exhibit nodular opacities with a
predilection for the upper lung zones [sarcoidosis,
chronic hypersensitivity pneumonitis, silicosis,
berylliosis, RA (necrobiotic nodular form), ankylosing
spondylitis].
 Presence of honeycomb appearance indicates poor
prognosis
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26.  Radiography
 A variety of infectious processes cause interstitial
opacities
fungal pneumonias (eg, coccidioidomycosis,
cryptococcosis, Pneumocystis jirovecii),
atypical bacterial pneumonias, and viral pneumonias.
 These infections often occur in immunocompromised
hosts
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27. Diagnosis
 Radiography- HRCT
 HRCT is superior to CXR in that
Early detection and confirmation of the disease
Better assessment of extent and distribution of
the lesions
Useful even in patients with normal chest
radiograph
Can better detect the presence of concomitant
condition like mediastinal adenopathy,
carcinoma…
Can preclude and be useful before lung biopsy
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28.  Radiography- HRCT
Certain HRCT findings help to narrow the differential
diagnosis of ILD.
 Bilateral symmetric hilar adenopathy and upper lung
zone reticular opacities suggest sarcoidosis or another
granulomatous disease
 Pleural plaques with linear calcification suggest
asbestosis
 Centrilobular nodules that spare the subpleural region
are seen in hypersensitivity pneumonitis, sarcoidosis,
Langerhans cell histiocytosis and also respiratory,
follicular, and cellular bronchiolitis
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29. ❖A complete lack of pulmonary parenchymal changes on
HRCT imaging virtually excludes a diagnosis of ILD
❖But, it may rarely still be present with microscopic
involvement.
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30.  Gallium-67 lung scanning — Gallium-67 lung scanning is
of limited value as a means of evaluating patients with
ILD. We do not obtain gallium-67 lung scans in the
evaluation of patients with ILD.
 FDG-PET scanning — The role of (18)F-2-deoxy-2-
fluoro-D-glucose (FDG) positron emission tomography
(PET) scanning in the evaluation of ILD is unclear. In a
series of 35 patients with pulmonary lymphangitic
carcinomatosis, diffuse uptake of FDG was noted in 30
patients and focal uptake in four. However, positive FDG
uptake can also be seen in sarcoidosis and pulmonary
Langerhans cell histiocytosis. We do not typically obtain
PET scans in the evaluation of ILD.
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31. Diagnosis
 PFT
 Most forms of ILD produce a restrictive defect with
reduced total lung capacity (TLC), functional residual
capacity, and residual volume
 FEV1 and FVC are reduced, related to the decreased
TLC
 FEV1/FVC ratio is usually normal or increased
 Lung volumes decrease as lung stiffness worsens with
disease progression
 Pulmonary function studies have been proved to have
prognostic value in patients with idiopathic interstitial
pneumonias, particularly IPF and nonspecific
interstitial pneumonia (NSIP)
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32. Diagnosis
 PFT
 In contrast, an interstitial pattern on chest radiograph
accompanied by obstructive airflow limitation (ie, a
reduced FEV1/FVC ratio) on lung function testing is
suggestive of any of the following processes:
➢ Sarcoidosis
➢ Lymphangioleiomyomatosis
➢ Hypersensitivity pneumonitis
➢ Pulmonary Langerhans cell histiocytosis
➢ Tuberous sclerosis and pulmonary
lymphangioleiomyomatosis
➢ Combined COPD and ILD
➢ Constrictive bronchiolitis
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33. Diagnosis
 Diffusion Capacity
 A reduction in the diffusing capacity of the lung
for carbon monoxide (DlCO) is a common but
nonspecific finding in most ILDs
 Moderate to severe reduction of DLCO in the
presence of normal lung volumes in a patient with
ILD suggests one of the following:
◼ Combined emphysema and ILD
◼ Combined ILD and pulmonary vascular disease
◼ Pulmonary Langerhans cell histiocytosis
◼ Pulmonary lymphangioleiomyomatosis
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34. Diagnosis
 DLCO
 Pulmonary vascular disease, and thus a reduction in
DLCO, can develop in patients with ILD as a
consequence of hypoxemic vasoconstriction,
thromboembolic disease complicating the ILD, or a
disease with both ILD and pulmonary hypertension,
such as scleroderma.
 In general, the severity of the DLCO reduction
does not correlate well with disease prognosis, unless
the DLCO is less than 35 percent of predicted
◼ Longitudinal changes in DLCO have been used to assess
disease progression or regression. Due to difficulties with
reproducibility in measuring DLCO, a change of 15 percent
is needed to identify a true change in disease severity
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35. Diagnosis
 Arterial Blood Gas
 Resting: May be normal or reveal hypoxemia
(secondary to a mismatching of ventilation to
perfusion) and respiratory alkalosis.
 A normal resting arterial O2 tension 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
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36. Diagnosis
 Exercise Testing
 Normal values for resting arterial partial pressure of
oxygen (PaO 2 ) or pulse O 2 saturation do not rule out
significant hypoxemia during exercise or sleep.
 Thus, it is important to perform exercise testing with
serial measurement of arterial blood gases or pulse
oximetry
 Cardiopulmonary exercise testing with measurement of
arterial blood gases to detect abnormalities of gas
exchange (b/c hypoxemia may not be seen at rest)
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37. Diagnosis
 Exercise Testing
 Exercise testing may take the form of a
cardiopulmonary exercise test, a six-minute
walk test, or informal ambulatory oximetry
including a stair climb to replicate the
patient's usual daily activity.
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38.  BAL
 Virtually all patients presenting with hemoptysis and
radiographic ILD should undergo BAL promptly to
confirm an alveolar source of bleeding and identify
any infectious etiologies.
 The majority of patients with an acute onset of ILD
will undergo BAL to evaluate for acute eosinophilic
pneumonia, alveolar hemorrhage, malignancy, and
opportunistic or atypical infection, which can often
be diagnosed on the basis of BAL findings
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39.  BAL
 The right middle lobe or lingula of the left upper
lobe are likely the best regions
 Ground glass opacification or profuse nodular
change are more likely to provide useful diagnostic
information
 BAL fluid and sediment can be analyzed for
infection or the presence of malignant cells, and
the gross appearance of freshly retrieved BAL
fluid may provide diagnosistic information
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40. Disease category Examples Findings in BAL fluid
Malignancy Lymphangitic carcinomatosis Malignant cells
Bronchioloalveolar cell carcinoma Malignant cells
Pulmonary lymphoma Malignant cells
Diseases due to inhaled (exogenous)
material
Lipoid pneumonia Fat globules in macrophages (oil-red-
O-stain)
Multinucleated giant cells
Asbestosis Ferruginous bodies
Silicosis Dust particles seen by polarized
microscopy
Berylliosis Positive lymphocyte transformation
test to beryllium salts
Inflammatory Diffuse alveolar hemorrhage Large numbers of erythrocytes
Hemosiderin-laden macrophages (iron
stain)
Sequential lavages progressively
more hemorrhagic
Chronic eosinophilic pneumonia Eosinophils ≥40 percent
Idiopathic acute eosinophilic
pneumonia
Eosinophils ≥25 percent
Pulmonary alveolar proteinosis Lipoproteinaceous material (periodic
acid-Schiff stain)
Pulmonary Langerhans cell
histiocytosis (Histiocytosis X)
Monoclonal antibody (T6) positive
histiocytes
CD1 positive Langerhans cells >5
percent
Birbeck granules in lavaged
macrophages (seen by electron
microscopy)
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41. High count (≥25 percent)
➢Chronic eosinophilic pneumonia (≥40 percent)
➢Churg Strauss syndrome with active pneumonitis
➢Idiopathic acute eosinophilic pneumonia (≥25 percent)
➢Tropical pulmonary eosinophilia (40 to 70 percent)
Mild to moderate counts (<25 percent)
➢Connective tissue disease
➢Drug-induced pneumonitis
➢Fungal pneumonia
➢Idiopathic pulmonary fibrosis (<10 percent)
➢Pulmonary Langerhans cell histiocytosis
➢Sarcoidosis
Interstitial lung disease associated with BAL
Eosinophilia
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42. ➢Idiopathic pulmonary fibrosis (15 to 40 percent)
➢Cryptogenic organizing pneumonia (40 to 70 percent)
➢Inorganic dust diseases
➢Asbestosis
➢Silicosis
➢Cigarette smoking (<10 percent)
➢Pulmonary Langerhans cell histiocytosis (Histiocytosis
X)
➢Hypersensitivity pneumonitis (acute)
➢Sarcoidosis (advanced)
Interstitial lung disease associated with BAL
Neutrophilia
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43. ➢ Hypersensitivity pneumonitis (60 to 80 percent)
➢ Sarcoidosis (Acute - 40 to 60 percent)
➢ Idiopathic pulmonary fibrosis (15 to 30 percent)
➢ Berylliosis
➢ Granite workers
➢ Amiodarone pneumonitis
➢ Lymphoma/Pseudolymphoma
➢ Pulmonary Langerhans cell histiocytosis (Early)
Interstitial lung disease associated with BAL
Lymphocytosis
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44. Diagnosis
 Lung biopsy is the most effective method for
confirming the diagnosis and assessing disease
activity
 Lung biopsy: 3 types
◼ Transbronchial (fibreoptic bronchoscopy)
◼ Video Assisted thoracic surgery (VATS)
◼ Surgical Lung Biopsy (SLB)
 Adequate sized multiple (4-8) biopsies should be
taken from at least 2 lobes
◼ Avoid areas with extensive fibrosis*
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45. Diagnosis
 Lung biopsy- complications
 Open lung biopsy in patients with suspected ILD has
approximately a 4.3% 30-day mortality rate, whereas
VATS biopsy appears to be safer with an associated
30-day mortality that is somewhat lower than open
biopsy but not negligible at approximately 2.1%
 Additionally, the highest mortality risk may occur in
patients whose ultimate diagnosis is IPF
◼ And SLB in patients with IPF has been reported to trigger
an acute exacerbation of IPF
◼ However, confirming the diagnosis and differentiating among
specific forms of IIP may not be possible without
performing SLB.
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46. Diagnosis
 Lung Biopsy- Contraindications
 Serious cardiovascular condition
 Honeycombing
 Radiographic evidence of end stage disease
 Severe Pulmonary dysfunction
 Major operative risks eg. Elderly
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47. Diagnosis
 *Serology
 Usually a hypersensitivity precipitin panel like
➢anti-nuclear antibodies (ANA)
➢rheumatoid factor,
➢anti-topoisomerase and
➢anti-neutrophil cytoplasmic antibodies
(ANCA)
 Esophageal Manometry & PH
 awareness of abnormal GER Vs aspiration -> ILD
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48. Treatment
 Although the course of ILD is variable, progression is
common and often insidious
 Therapy does not reverse fibrosis
 The major goals of treatment are
 Permanent removal of the offending agent, when
known, and
 Early identification and aggressive suppression of the
acute and chronic inflammatory process, thereby
reducing further lung damage
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49. Treatment
 Hypoxemia (PaO2 <55 mmHg) at rest and/or
with exercise should be managed with
supplemental oxygen.
 Management of cor pulmonale may be
required as the disease progresses
 Pulmonary rehabilitation has been shown to
improve the quality of life in patients with
ILD
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50. Treatment
 Immunosuppressive anti-inflammatory agents are used to
treat various forms of ILD
 Treatment of any form of ILD with immunosuppressive
therapy is off-label in the U.S. and anti-inflammatory/
immunosuppressive pharmacologic therapy has not been
validated in placebo-controlled clinical trials
 However, there is reasonably compelling evidence that the
administration of agents such as corticosteroids is
strongly associated with improvement or even clearing of
lung pathology for many forms of ILD.
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51. Treatment
 This is particularly the case for disorders
such as cryptogenic organizing pneumonia
(COP), eosinophilic pneumonia, sarcoidosis,
or cellular non-specific interstitial
pneumonia (NSIP)
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52. Treatment
 Glucocorticoids
 Steriods are the mainstay of therapy though there
has not been a clinical trial supporting it
 Prednisolol 0.5-1mg/kg once daily dosing is started
and given for 4-12 weeks and patient reevaluated
after this time.
 Then if the patient is improving it should be
tapered to 0.25-0.5mg/kg and kept for 4-12 weeks.
 If the patient’s condition declines in this period,
other agents can be added like cyclophosphamide
and azathioprine.
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53. Treatment
 Cyclophosphamide and azathioprine (1–2 mg/kg
lean body weight per day), 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
 Lung transplantation can be considered for ILDs
which are chronic and irreversible despite therapy.
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54. Treatment
 When extensive fibrosis is present, such
therapies may be less efficacious, especially
for patients with IPF, for whom currently
available immunosuppressive or antifibrotic
therapies are not recommended
 However, some forms of CTD-associated ILD
(NSIP or UIP pathologies) have been reported
to respond to mycophenolate therapy, which
also allowed a significant lowering of
corticosteroid dosing
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55. Treatment
 Anti-fibrotic pharmacologic therapies are
being increasingly brought to clinical trials,
and patients should be encouraged to enroll
in clinical trials if they are found to have
IPF or other forms of advanced ILD for
which effective therapies have yet to be
identified and clinical trials for their
specific form of ILD are open to enrollment.
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56. Treatment
 Lung transplantation
 Lung transplantation is an accepted form of
treatment for patients with ILD that is
progressive, clearly leading to respiratory
failure, and refractory to other therapies
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57. Follow-up
 Measurements that can be made periodically
to objectively assess changes in physiologic
function over time include
 Formal dyspnea assessment tools,
 The forced vital capacity (FVC),
 Diffusion capacity of the lung for carbon
monoxide (DLCO), and
 The 6-minute walk test (6-MWT) distance and
oxyhemoglobin saturation change
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58. Follow-up
 The baseline FVC value has not been shown to
correlate well with disease course for patients with
IPF, but change in FVC over time has been show to
correlate well with stable versus progressive disease
with greater than 10% decline considered to be
significant and indicative of disease progression
 A decline of ≥15% in DLCO has also been correlated
with disease progression in IPF, and declining 6-MWT
distance or oxyhemoglobin saturation are also
associated with disease progression
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59. Follow-up
 More recent analyses suggest that changes in
FVC that are less than 10% may represent
important clinical change, and using relative
change rather than absolute change in FVC
values may provide a better indication of
clinical response
 Biomarkers
 Biomarkers that reflect disease severity and
correlate with prognosis have been reported for
IPF, but these have yet to be validated for use in
the clinical setting
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60. Follow-up
 HRCT for follow-up
 In addition to its utility in diagnosis, HRCT can
be scored for the extent/severity of fibrosis,
and the fibrosis severity scoring has been
shown to correlate with prognosis
 However, the use of serial HRCT scanning has
not been validated as a useful gauge of disease
progression over time for IPF and presents a
significant radiation risk to the patient.
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62. Refrences
 Harrison principle of Medicine 20th ed.
 Upto date 21.6
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63. ???
+++
suggestion /recommendation
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