Interstitial lung diseases (ILDs) represent a heterogeneous group of over 200 lung disorders that involve the parenchyma of the lungs. ILDs can be caused by various factors including hazardous exposures, autoimmune diseases, infections, and idiopathic factors. Clinically, ILDs present with dyspnea, cough, and crackles on exam. Diagnosis involves imaging such as chest X-ray and HRCT which show patterns of reticular opacities, honeycombing, and fibrosis. Pulmonary function tests typically show a restrictive defect. Precise diagnosis requires consideration of clinical features, imaging patterns, and sometimes lung biopsy.

1. INTERSTITIAL LUNG
DISEASES
Jan 9th, 2023
Presentor: Awatif Bashir
(R1)
Moderator: AbdulAziz M.
(Internist)

2. Table of Contents
1. Introduction
2. Overview
3. Epidemiology
4. Etiology
5. Pathogenesis
6. Clinical Picture
7. Diagnosis
8. Management

3. 01
INTRODUCTION
&
OVERVIEW

4. OVERVIEW
• Interstitial Lung Diseases ILDs represents a vast spectrum of
lung parenchymal disease including >200 known individual
Diseases identified and classified based on many different
properties.
• For the sake of this presentation, an overall overview of
ILDs will be discussed containing the main points of these
diseases as a group and not in individual diseases form.

5. INTRODUCTION
o DEFINITION: ILD’s are a heterogeneous group of
disorders classified together because of similar
clinical, radiographic, physiologic, or pathologic
manifestations.
o They involve the parenchyma of the lung—the alveoli,
the alveolar epithelium, the capillary endothelium,
and the spaces between those structures and
perivascular and lymphatic tissues.

6. INTRODUCTION
o These diseases are sometimes referred to as
“Diffuse Parenchymal Lung Diseases DPLD”
to establish the point that the interstitium isn’t the
only lung compartment affected by them.

7. INTRODUCTION
o These Diseases are Characterized By:
1. Radiologically:
• Diffuse infiltrations
2. Histologically:
• Distortion of gas exchanging units
3. Physiologically:
• Restriction of lung volumes and impaired oxygenation

9. 02
EPIDEMIOLOGY
&
ETIOLOGY

10. EPIDEMIOLOGY
1. Among persons >18 years, the prevalence of all ILDs is
about 120 per 100,000 men and 80 per 100,000
women.
2. The prevalence of undiagnosed or early ILD is
estimated to be 10 times that of clinically recognized
disease
3. Among the ILDs, the most common is idiopathic
pulmonary fibrosis, which represents at least 30%
of incident cases

11. ETIOLOGY
• ILDs can be caused by various of mechanisms leading to
various disease processes. And most of them are Idiopathic
with no identified cause:
• Among the Known causes:
• Hazardous Material Exposure
• Metals Exposure
• Autoimmune Diseases
• Inhaled gases

12. Lung Response: Alveolitis, Interstitial Inflammation, and Fibrosis
Known Cause
Asbestos
Fumes, gases
Drugs (antibiotics, amiodarone, gold)
and chemotherapy drugs
Radiation
Aspiration pneumonia
Residual of acute respiratory distress
syndrome
Smoking-related
Desquamative interstitial pneumonia
Respiratory bronchiolitis–associated
ILD
Langerhans cell granulomatosis
(eosinophilic granuloma of the lung)

13. Lung Response: Alveolitis, Interstitial Inflammation, and Fibrosis
Unknown Cause
Idiopathic interstitial pneumonias
Idiopathic pulmonary fibrosis (usual
interstitial pneumonia)
Acute interstitial pneumonia (diffuse
alveolar damage)
Cryptogenic organizing pneumonia
(bronchiolitis obliterans with organizing
pneumonia)
Nonspecific interstitial pneumonia Connective
tissue diseases
SLE, RA, ankylosing spondylitis, systemic
sclerosis, Sjögren's syndrome,
polymyositis-dermatomyositis
Pulmonary hemorrhage syndromes
Goodpasture's syndrome, idiopathic
pulmonary hemosiderosis, isolated
pulmonary capillaritis
Pulmonary alveolar proteinosis
Lymphocytic infiltrative disorders
(lymphocytic interstitial pneumonitis
associated with connective tissue disease)
Eosinophilic pneumonias
Lymphangioleiomyomatosis
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-versus-host disease (bone marrow
transplantation; solid organ
transplantation)

14. Lung Response: Granulomatous
Known Cause
Hypersensitivity pneumonitis (organic
dusts)
Inorganic dusts: beryllium, silica
Unknown Cause
Sarcoidosis
Granulomatous vasculitides
Granulomatosis with polyangiitis
(Wegener's), allergic granulomatosis of
Churg-Strauss
Bronchocentric granulomatosis
Lymphomatoid granulomatosis

15. ETIOLOGY
 Of the various causes mentioned above, the important or
mention worthy ones are:
 Primary or Idiopathic:
a.Idiopathic Pulmonary Fibrosis
b.Nonspecific interstitial pneumonia (NSIP)
c.Organizing pneumonia (OP)
d.Respiratory bronchiolitis (RB)
e.Diffuse alveolar damage (DAD)
f.Desquamative interstitial pneumonia (DIP)
g.Lymphocytic interstitial pneumonia (LIP)

16. ETIOLOGY
 Secondary Causes:
a. Hypersensitivity pneumonitis
b. Pneumoconiosis
c. Drug induced
d. Radiation induced

17. ETIOLOGY
 The most common ILDs of unknown etiology are:
 Sarcoidosis
 IPF and
 Pulmonary fibrosis associated with connective tissue diseases.
 And the most common ILDs of known etiology are:
 Environmental related ILDs
 Occupational related ILDs

18. 03
PATHOGENESIS

19. PATHOGENESIS
o These are nonmalignant disorders and are not caused by
identified infectious agents.
o The precise pathway(s) leading from injury to fibrosis is not
known.
o Injury initiating agents are multipleand lead o limited
Immunopathogenic responses of lung tissue
o The mechanisms of repair of lung tissues have common
features

21. PATHOGENESIS
1. Inflammation and Fibrosis
a. Initial Insult: an injury to the epithelial surface that
causes inflammation in the air spaces and alveolar walls
b. As time goes by, disease becomes more chromic and the
inflammation spreads to adjacent portions of the
interstitium and vasculature and eventually causes
interstitial fibrosis.

22. PATHOGENESIS
Important histopathologic patterns in these ILDs:
 Usual interstitial pneumonia (UIP)
 Nonspecific interstitial pneumonia
 Respiratory bronchiolitis/desquamative interstitial
pneumonia
 Organizing pneumonia
 Diffuse alveolar damage (acute or organizing) and
 Lymphocytic interstitial pneumonia

23. PATHOGENESIS
1. Granulomatous Lung Disease
a. Characterized by Accumulation of immune cells (T
Lymphocytes, Epithelioid cells, Macrophages) that form
granulomas in the lung parenchyma.
b. Progression of these granulomatous lesions leads to fibrosis
c. Because it’s a slowly progressing process, many patients
with granulomatous lung disease remain free of severe
impairment of lung function or, when symptomatic,
improve after treatment
Main Differentials : Sarcoidosis and hypersensitivity
pneumonitis

24. 04
CLINICAL
PICTURE

25. OVERVIEW
• Although these disease can present differently based on
the type of damage and the area of impairment in the lung,
the clinical picture can be evaluated looking into:
1. History
2. Symptoms
3. Physical Exam Finding

26. HISTORY
• The common points looked into in these patient’s Histories
are
1. Age
2. Family History
3. Gender
4. Duration of Illness
5. Smoking History
6. Intensity of Symptoms
7. Drug History
8. Occupational History

27. HISTORY
1. Age
o Some of the ILDs are more common in certain age groups:
o Age 20-40 years - Sarcoidosis
- CTD-ILD
- LAM
o > 50years - Idiopathic pulmonary fibrosis
2. Family History
- IPF
- Sarcoidosis

28. HISTORY
3. Gender
• Premenopausal female:
LAM (lymphangioleiomatosis)
• Male predominant:
ILD associated with RA
Pneumoconiosis
4. Duration
a. Insidious over months or years (e.g., IPF)
b. Acute (less than 3 weeks) (e.g. drug
reaction, acute hypersensitivity
pneumonitis, chemical exposure)
c. Subacute: 3-12 weeks (e.g. iBoop)

29. Duration of Illness Prior to Diagnosis
Acute (days to weeks) < 3 WKS
AIP, (Hamman-Rich syndrome)
Eosinophilic pneumonia
Hypersensitivity pneumonitis
Bronchiolitis obliterans with organizing pneumonia
Subacute (weeks to months) 3-12 WKS
Sarcoidosis
Some drug-induced ILDs
Alveolar hemorrahge syndromes
Idiopathic bronchiolitis obliterans with organizing pneumonia
Connective tissue disease (SLE or polymyositis)
Chronic (months to years) >12 WKS
Idiopathic pulmonary fibrosis
Sarcoidosis
Pulmonary histocytosis X

30. HISTORY
5. Smoking History
o Diseases associated with smokers:
- Pulmonary langhren cell histiocytosis
- Desquamative interstitial pneumonitis
- Respiratory broncholitis
o Diseases less likely to be seen in smoker:
- Hypersensitivity pneumonitis
- Sarcoidosis
o Pulmonary Hemorrhage is far more frequent in current
smokers, with Good Pasture’s syndrome.

31. HISTORY
6. Intensity of Symptoms
i. Minimal symptoms in the presence of grossly
abnormal chest radiograph (e.g., sarcoidosis).
ii. Severe symptoms in the presence of mild
radiograph abnormalities (e.g., IPF, HP).
iii. Sudden worsening of dyspnea (particularly if
associated with pleural pain) may indicate
spontaneous pneumothorax.
7. Drug History

32. HISTORY
8. Occupational History
• Each of the following requires specific exposure:
1. Pneumoconiosis
2. Drug induced ILD
3. 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.
• A list of possible agent to which the patient may have been
exposed.

35. SYMPTOMS OF ILDs
1. Dyspnea
2. Cough:
A dry cough is common and seen
in conditions that involve the
airways
Productive cough is unusual.
3. Wheezing
is an uncommon symptoms:
-Chronic eosinophilic pneumonia
-Churg-Strauss syndrome
-Respiratory bronchiolitis
4.Fever: IPF, RA, PSS are
almost never associated with
fever
5. Chest pain is an uncommon
symptom:
-Pleuritic chest pain may occur in
ILD, associated with RA/SLE, drug-
induced disorders
-Substernal discomfort is common in
sarcoidosis
6. Hemoptysis: invokes the
differential diagnosis of diffuse
alveolar haemorrhage syndromes,
granulomatous vasculitides.
- New onset of hemoptysis in a
patient with known ILD suggests a
complicating malignancy, PE or
infection

36. SYMPTOMS OF ILDs
7.Extra thoracic manifestations:
i. Nasal discharge or other upper airway
symptoms that suggest Wegener’s
granulomatosis.
ii Arthritis: CVD, sarcoidosis or granulomatous
vasculitides.
iii. Skin rashes: common to sarcoidosis, CVD
and granulomatous vasculitis.

37. PHYSICAL ECAMINATION FINDINGS
Respiratory system exam
o Tachypnea,
o Finger clubbing - IPF
o Crackles
o Scattered late inspiratory high-pitched rhonchi, so-called inspiratory
squeaks
o Cyanosis in late course
Cardiac examination
1. Usually normal except in more advanced stages of pulmonary fibrosis
When findings of pulmonary hypertension and cor-pulmonale (augmented P2,
right-sided lift, right-sided gallop) may become evident
• Pulmonary hypertension may also be a primary manifestation of some
connective tissue disorders (eg, progressive systemic sclerosis).

41. 05
DIAGNOSIS

42. INVESTIGATIONS
Laboratory tests
1. CBC
2. Abnormal RFT -pulmonary-renal syndromes
3. Serum electrolyte
4. Urine analysis
5. HIV testing
6. ANA, rheumatoid factor, anti-topoisomerase
(anti-Scl70), and anti-neutrophil cytoplasmic
antibodies (ANCA)

43. Abnormality Associated Condition
Leukopenia Sarcoidosis, connective tissue disease, lymphoma, drug-induced
Eosinophilia Eosinophilic pneumonia, sarcoidosis, systemic vasculitis, drug-induced
(sufa, methotrexate)
Thrombocytopenia Sarcoidosis, connective tissue disease, drug-induced, Gaucher’s
Hemolytic anemia Connective tissue disease, sarcoidosis, lymphoma, drug-induced
Normocytic anemia Diffuse alveolar hemorrhage syndromes, connective tissue
lymphangitic carcinomatosis
Urinary sediment abnormalities Connective tissue disease, systemic vasculitis, drug-induced
Hypogammaglobulinemia Lymphocytic interstitial pneumonitis
Hypergammaglobulinemia Connective tissue disease, sarcoidosis, systemic vasculitis, lymphocytic
interstitial pneumonia, lymphoma
Serum immune complexes Idiopathic pulmonary fibrosis, lymphocytic interstitial pneumonitis,
vasculitis, connective tissue disease, eosinophilic granuloma
Serum angiotensin-converting enzyme Sarcoidosis, hypersensitivity pneumonitis, silicosis, Gauche’s dz
Antibasement membrane antibody Goodpasture’s syndrome
Antineutrophil cytoplasmic antibody Wegener’s granulomatosis, Churg-Strauss syndrome, microscopic
polyangitis
Serum precipitating antibodies Hypersensitivity pneumonitis
Lymphocyte transformation test Chronic beryllium disease, aluminum-potroom workers disease,
pneumonitis
Elevation of LDH Alveolar proteinosis, idiopathic pulmonary fibrosi

44. IMAGING
1. CXR findings include
a. a bibasilar reticular pattern
b. A nodular or mixed pattern of alveolar filling and increased reticular
markings
c. subgroup of ILDs exhibit nodular opacities with a predilection for the
upper lung zones [sarcoidosis, PLCH, chronic hypersensitivity
pneumonitis, silicosis, berylliosis, RA (necrobiotic nodular form),
ankylosing spondylitis].
Presence of honeycomb appearance indicates poor prognosis
o A variety of infectious processes cause interstitial opacities on chest
radiograph, including fungal pneumonias (eg, coccidioidomycosis,
cryptococcosis, Pneumocystis jirovecii), atypical bacterial
pneumonias, and viral pneumonias.
o These infections often occur in immunocompromised hosts

45. CXR PATTERNS

46. CXR PATTERNS

47. CXR PATTERNS

48. CXR PATTERNS

50. IMAGING
2. HRCT
a. HRCT is superior to CXR in that
i. Early detection and confirmation of the disease
ii. Better assessment of extent and distribution of the lesions
iii. Useful even in patients with normal chest radiograph
iv. Can better detect the presence of concomitant condition
like mediastinal adenopathy, carcinoma…
v. Can preclude and be useful before lung biopsy

51. RETICULAR INFILTRATES

52. HONEYCOMB LUNG

53. IPF on HRCT
On HRCT, a confident diagnosis of IPF is based on the presence of bilateral,
predominantly subpleural, and basal reticular opacities with associated traction
bronchiectasis and honeycombing in the absence of small nodules or extensive
ground-glass opacity .this is known as “confident” pattern of IPFon HRCT.

54. PULMONARY FUNCTION TESTS
Spirometry Shows:
 Most forms of ILD produce a restrictive defect with reduced total lung
capacity (TLC), functional residual capacity, and residual volume
 Forced expiratory volume in one second (FEV1) and forced vital
capacity (FVC) are reduced, but these changes are 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)

55. PULMONARY FUNCTION TESTS
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:
i. Sarcoidosis
ii. Lymphangioleiomyomatosis
iii. Hypersensitivity pneumonitis
iv. Pulmonary Langerhans cell histiocytosis
v. Tuberous sclerosis and pulmonary
lymphangioleiomyomatosis
vi. Combined COPD and ILD
vii. Constrictive bronchiolitis

56. DIFFUSION CAPACITY (DLCO)
a. A reduction in the diffusing capacity of the lung for
carbon monoxide (DlCO) is a common but nonspecific
finding in most ILDs
b. Moderate to severe reduction of DLCO in the presence of
normal lung volumes in a patient with ILD suggests one of
the following:
i. Combined emphysema and ILD
ii. Combined ILD and pulmonary vascular disease
iii. Pulmonary Langerhans cell histiocytosis
iv. Pulmonary lymphangioleiomyomatosis

57. ARTERIAL BLOOD GASES
a. Resting: May be normal or reveal hypoxemia
(secondary to a mismatching of ventilation to
perfusion) and respiratory alkalosis.
b. A normal resting arterial O2 tension does not rule
out significant hypoxemia during exercise or sleep
c. Carbon dioxide (CO2) retention is rare and is
usually a manifestation of end-stage disease

58. FIBEROPTIC BRONCHOSCOPY AND
BRONCHOALVEOLAR LAVAGE (BAL)
1. Lymphocyte-predominant
sarcoidosis or hypersensitivity pneumonitis
1. Eosinophils
pulmonary Langerhans cell granulomatosis,
1. An asbestos body count greater than 1 fiber per
milliliter of BAL fluid is seen in asbestosis

59. 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

60. LUNG BIOPSY
1. Fiberoptic bronchoscopy with multiple
transbronchial lung biopsies (four to eight
biopsy samples)
2. Video-assisted thoracoscopic biopsy or open
lung biopsy
3. Relative contraindications are serious CVD,
honeycombing , severe pulmonary
dysfunction,
4. Mortality rate is 1%

61. LUNG BIOPSY
1. Lung Biopsy- Contraindications
a. Serious cardiovascular condition
b. Honeycombing
c. Radiographic evidence of end stage disease
d. Severe Pulmonary dysfunction
e. Major operative risks eg. Elderly

62. 06
MANAGEMENT

63. GOALS OF TREATMENT
1. Permanent removal of the offending agent, when known,
2. Early identification and aggressive suppression of the
acute and chronic inflammatory process, thereby reducing
further lung damage.
3. Supplemental oxygen for hypoxemia (PaO2<55 mmHg)
4. Pulmonary rehabilitation
5. Management of cor pulmonale may be required as the
disease progresses

64. MEDICAL TREATMENT
1. Glucocorticoids
a. Steriods are the mainstay of therapy though there has not been
a clinical trial supporting it
b. Prednisolol 0.5-1mg/kg once daily dosing is started and given
for 4-12 weeks and patient reevaluated after this time.
c. Then if the patient is improving it should be tapered to 0.25-
0.5mg/kg and kept for 4-12 weeks.
d. If the patient’s condition declines in this period, other agents
can be added like cyclophosphamide and azathioprine.

65. MEDICAL TREATMENT
1. 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.
2. An objective response usually requires at least 8–12 weeks to
occur
a. Lung transplantation can be considered for ILDs which
are chronic and irreversible despite therapy.

66. 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

67. FOLLOW-UP
1. Measurements that can be made periodically to objectively
assess changes in physiologic function over time include
a. Formal dyspnea assessment tools,
b. The forced vital capacity (FVC),
c. Diffusion capacity of the lung for carbon monoxide
(DLCO), and
d. The 6-minute walk test (6-MWT) distance and
oxyhemoglobin saturation change

68. ● Harrison 21st Edition
● Uptodate
● Medscape
● Infographics from Internet
Resources

69. THANK YOU
QUESTIONS???