Interstitial Lung Disease:

Overview and Approach

Selam B

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• the interstitial lung diseases (ILDs)(AKA diffuse parenchymal lung
disease, are a heterogeneous group of disorders that are classified
together because of similar :

• clinical, radiographic, physiologic, or pathologic manifestations.

• 100s of diseases.

• most of these disorders are also associated with extensive alteration

of alveolar and airway architecture
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• The treatment choices and prognosis vary among the different causes
and types of ILD, so ascertaining the correct diagnosis is important.

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• Patients with ILD commonly come to clinical attention in one of the
following ways:

• Symptoms of progressive breathlessness with exertion (dyspnea) or a persistent

nonproductive cough.

• Pulmonary symptoms associated with another disease, such as a connective

tissue disease

• History of occupational exposure (eg, asbestosis, silicosis)

• An abnormal chest imaging study

• Lung function abnormalities on simple office spirometry, particularly a restrictive

ventilatory pattern (ie, reduced total lung capacity and forced vital capacity).
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 DIAGNOSTIC APPROACH TO ILD
• Diagnosis is based upon :
• History,

• Physical examination,

• Laboratory data

• PFT

• radiography,

• BAL and

• Lung biopsy

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DX APPROACH………HISTORY …..Age
Younger (20-40) Older (>50)

sarcoidosis Idiopathic pulmonary fibrosis (IPF)

connective tissue disease-associated ILD

lymphangioleiomyomatosis(LAM)

Pulmonary Langerhans cell histiocytosis (LCH)

Inherited forms of ILD (familial IPF, Gaucher's disease,

Hermansky-Pudlak syndrome)

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 DX APPROACH………HISTORY
…..Gender
Females Males

Lymphangioleiomyomatosis(LAM) (premenopausal) ILD associated with rheumatoid arthritis

pulmonary involvement in tuberous sclerosis (premenopausal) Pneumoconiosis.

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DX APPROACH………HISTORY …..Duration of Smx

• Acute (days to weeks)

• Acute idiopathic interstitial pneumonia (AIP, Hamman-Rich syndrome)
• Acute Eosinophilic pneumonia
• Acute Hypersensitivity pneumonitis
• Cryptogenic organizing pneumonia
• Acute exacerbation of idiopathic pulmonary fibrosis or other ILDs

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 DX APPROACH………HISTORY …..Duration of Smx
• Subacute (weeks to months) to Chronic (months to years)

• Sarcoidosis

• Some drug-induced ILDs, Radiation

• Alveolar hemorrhage syndromes

• Cryptogenic organizing pneumonia

• Connective tissue disease (systemic lupus erythematosus or polymyositis)

• Idiopathic pulmonary fibrosis

• Pulmonary Langerhans cell histiocytosis

• Chronic hypersensitivity pneumonitis 10

DX APPROACH………HISTORY …..snx/smx

• wheezing
• hypersensitivity pneumonitis
• eosinophilic pneumonia,
• sarcoidosis

• Substernal chest pain…… sarcoidosis

• Pleuritic chest pain ……in a patient with connective tissue disease,

• pneumothorax in cystic lung diseases…….LAM and LCH

• Hemoptysis…………….diffuse alveolar hemorrhage,

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DX APPROACH………HISTORY …..systemic
snx/smx
• night sweats, fever, fatigue, or weight loss suggest an underlying
inflammatory condition.

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DX APPROACH………HISTORY …..dermatologic
sn/sm
• Dermatomyositis…..heliotrope rash, Gottron’s papules, or “mechanic’s
hands,”

• Systemic sclerosis (scleroderma)….skin tightness and thickening,

telangiectasias, Raynaud’s phenomenon, or digital pitting.

• Sarcoidosi…..Papular eruptions, lupus pernio, and erythema nodosum

• SLE…. malar rash, photosensitivity skin reaction, or hair loss

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 DX APPROACH………HISTORY …..Musculoskeletal sn/sm
• Rheumatoid arthritis, Sjögren syndrome, or mixed connective tissue
disorder
• arthralgias,
• morning stiffness, joint swelling and erythema, and deformities

• systemic sclerosis and polymyositis…Swollen fingers (“sausage digits”)

• scleroderma, mixed connective tissue disease, SLE, and antisynthetase

syndrome…Raynaud’s phenomenon

• Clubbing
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DX APPROACH………HISTORY …..Neurologic/Ophthalmologic pic

• Sjögren syndrome….. Dry eye

• SLE or sarcoidosis…….. Uveitis

• SLE, vasculitis or sarcoidosis…… Neurologic symptoms

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DX APPROACH………Hx/PE …..cvs
• c/p of Corpulmonale in long standing Chronic ILDs

• Accentuated p2 (Pulmonary HTN as secondary or related to the

primary disease)

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 Physical findings Associated conditions

Systemic rheumatic disease, neurofibromatosis, anti-GBM antibody

Systemic arterial hypertension
syndrome, systemic vasculitis

Skin
Discoid lupus IPF, SLE, drug-induced SLE

Drug-induced, amyloidosis, systemic rheumatic disease, Gaucher's

Maculopapular rash
disease

Heliotrope rash; Gottron papules; poikiloderma Dermatomyositis

Mechanic's hands Antisynthetase syndrome
Palmar papules, ulcerating lesions Amyopathic dermatomyositis

Telangiectasia, sclerodactyly, hyperpigmentation/hypopigmentation, Systemic sclerosis (scleroderma)

digital ulcers or pitting

Systemic rheumatic disease (scleroderma, SLE, mixed systemic

Raynaud phenomenon
rheumatic disease)

Cafe-au-lait spots, neurofibromas Neurofibromatosis

Cutaneous vasculitis (eg, palpable purpura) Systemic vasculitides; systemic rheumatic disease

Reticulated or mottled skin hyperpigmentation, nail dystropy, Dyskeratosis congenita

mucosal leukoplakia

Albinism Hermansky-Pudlak syndrome

Calcinosis Dermatomyositis-polymyositis; scleroderma

Subcutaneous nodules Rheumatoid arthritis, neurofibromatosis, ANCA-associated vasculitis

Erythema nodosum (deep, painful nodules predominantly on Sarcoidosis; systemic rheumatic disease; Behçet syndrome;
anterior surfaces lower extremities) inflammatory bowel disease; histoplasmosis, coccidioidomycosis 18
Eyes

Uveitis Sarcoidosis (eg, mutton-fat keratic precipitates), Behçet syndrome (eg,

panuveitis, hypopyon), ankylosing spondylitis (eg, acute anterior uveitis)

Scleritis ANCA-associated vasculitis, SLE, systemic sclerosis (scleroderma), sarcoidosis

Keratoconjunctivitis sicca Lymphocytic interstitial pneumonia (in Sjögren syndrome)

Cherry red macula, macular halo Neiman-Pick disease

Hematologic and reticuloendothelial system

Peripheral lymphadenopathy Sarcoidosis, lymphangitic carcinomatosis, lymphocytic interstitial pneumonia,

lymphoma, LAM-TSC

Hepatosplenomegaly Sarcoidosis, pulmonary Langerhans cell histiocytosis, systemic rheumatic

disease, amyloidosis, lymphocytic interstitial pneumonia

Anemia, thrombocytopenia, hypocellular marrow Dyskeratosis congenita

Heart

Pericarditis, pericardial effusion Radiation pneumonitis, systemic rheumatic disease, LAM-TSC

Cardiomyopathy ANCA-associated vasculitis, sarcoidosis, SLE

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Musculoskeletal/neurologic

Muscle weakness Systemic rheumatic disease, drugs (eg, statins), sarcoidosis

Nervous system abnormalities Pulmonary Langerhans cell histiocytosis, Neiman-Pick disease,

neurofibromatosis, sarcoidosis, SLE, systemic vasculitis, TSC

Arthritis ANCA-associated vasculitis, Rheumatoid arthritis, SLE, sarcoidosis

(predominantly periarthritis of ankles and knees)

Gastrointestinal/renal

Glomerulonephritis Anti-GBM antibody syndrome, ANCA-associated vasculitis, sarcoidosis

Nephrotic syndrome Amyloid, drug-induced, sarcoidosis, SLE

Renal mass (eg, angiomyolipoma) TSC, LAM

Gastrointestinal symptoms (eg, diarrhea, abdominal pain, hematochezia) Pneumonitis related to inflammatory bowel disease

Other

Salivary or lacrimal gland enlargement Sarcoidosis, lymphocytic interstitial pneumonia (in Sjögren syndrome), IgG4-
related disease

Pleural abnormalities Systemic rheumatic disease, LAM-TSC (chylous effusion), abestosis

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 Smoking history
• Largely among current or former smokers
• pulmonary Langerhans cell histiocytosis,
• desquamative interstitial pneumonitis,

• respiratory bronchiolitis-interstitial lung disease, and

• idiopathic pulmonary fibrosis

• Among never or former smokers

• sarcoidosis and

• hypersensitivity pneumonitis 21
PAST MEDICAL HISTORY
• connective tissue disease

• HIV

• kidney disease(vasculitis, pulmonary–renal syndromes, or connective

tissue disease)

• liver disease(sarcoidosis)

• Facial palsy (sarcoidosis)

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 FAMILY HISTORY
• Most forms of ILD are not heritable, though several do have a genetic
component.

• When heritable disease is suspected, it is important to consider both

systemic disorders as well as those that primarily affect the lung.

• idiopathic pulmonary fibrosis (IPF),

• tuberous sclerosis
• neurofibromatosis
• Niemann-Pick disease
• Gaucher's disease
• Hermansky-Pudlak syndrome
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Occupational and environmental
exposures history
• The occupational history should be thorough, including a review of all
jobs held in the past.

• In particular, attention should be paid to any occupation in which a

history of exposure to organic or inorganic products was present.

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Medication/radiation history http://www.pneumotox

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 CHEST IMAGING
HRCT Than CXR

Normal

Hypersensitivity pneumonitis

Sarcoidosis

Bronchiolitis obliterans

Asbestosis

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Peripheral lung zone

Idiopathic pulmonary fibrosis

Asbestosis

Connective tissue disease

Cryptogenic organizing pneumonia

Eosinophilic pneumonia

Central disease (bronchovascular thickening)

Sarcoidosis

Lymphangitic carcinoma

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Upper zone predominance

Granulomatous disease

Sarcoidosis

Pulmonary histiocytosis X (eosinophilic granuloma)

Chronic hypersensitivity pneumonitis

Chronic infectious diseases (eg, tuberculosis, histoplasmosis)

Pneumoconiosis

Silicosis

Berylliosis

Coal miners' pneumoconiosis

Lower zone predominance

Idiopathic pulmonary fibrosis

Rheumatoid arthritis (associated with usual interstitial pneumonia)

Asbestosis 30
Airspace opacities

Haze or ground glass attenuation

Hypersensitivity pneumonitis

Desquamative interstitial pneumonia

Respiratory bronchiolitis-associated interstitial lung disease

Drug toxicity

Pulmonary hemorrhage

Lung consolidation

Chronic or acute eosinophilic pneumonia

Cryptogenic organizing pneumonia (bronchiolitis obliterans with organizing pneumonia)

Aspiration (lipoid pneumonia)

Alveolar carcinoma

Lymphoma

Alveolar proteinosis 31
Reticular opacities

Idiopathic pulmonary fibrosis

Asbestosis

Connective tissue disease

Hypersensitivity pneumonitis

Nodules

Hypersensitivity pneumonitis

Respiratory bronchiolitis-associated interstitial lung disease

Sarcoidosis

Pulmonary langerhans cell histiocytosis

Silicosis

Coal workers' pneumoconiosis

Metastatic cancer

Isolated lung cysts

Pulmonary langerhans cell histiocytosis

Lymphangioleiomyomatosis

Chronic Pneumocystis carnii (P. jirovecii) pneumonia

LIP 32
Radiographic Characteristics of the UIP Pattern

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Lab

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 PULMONARY FUNCTION TESTS
• assist in assessing the severity of disease and help determine
prognosis.

• The testing typically include spirometry, measurement of lung

volumes, and diffusing capacity.

• Exercise testing, such as the 6-minute walk test, is particularly

important for patients with ILD.

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 PULMONARY FUNCTION TESTS
• Typically, spirometry in most forms of ILD demonstrates a restrictive
ventilatory defect due to decreased compliance and increased recoil of
the lung parenchyma.

• The presence of obstruction suggests either concomitant obstructive lung

disease, often from prior smoking exposure, or the presence of an airway-
centered lung ILD such as LCH, LAM, or sarcoidosis.

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 BRONCHOALVEOLAR LAVAGE
• Bronchoalveolar lavage (BAL) is performed during flexible
bronchoscopy to obtain samples of cells and fluid from the distal
airways and alveoli.

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 Disease category Examples Findings in BAL fluid
Lymphangitic carcinomatosis Malignant cells
Malignancy Bronchioloalveolar cell carcinoma Malignant cells
Pulmonary lymphoma Malignant cells
Fat globules in macrophages (oil-red-O-
Lipoid pneumonia stain)
Multinucleated giant cells
Diseases due to inhaled (exogenous) Asbestosis Ferruginous bodies
material Dust particles seen by polarized
Silicosis microscopy
Positive lymphocyte transformation test
Berylliosis to beryllium salts
Large numbers of erythrocytes
Hemosiderin-laden macrophages (iron
Diffuse alveolar hemorrhage stain)
Sequential lavages progressively more
hemorrhagic
Chronic eosinophilic pneumonia Eosinophils ≥40 percent
Idiopathic acute eosinophilic pneumonia Eosinophils ≥25 percent
Inflammatory
Pulmonary alveolar proteinosis Lipoproteinaceous material (periodic acid-
Schiff stain)
Monoclonal antibody (T6) positive
histiocytes
Pulmonary Langerhans cell histiocytosis CD1 positive Langerhans cells >5 percent
(Histiocytosis X)
Birbeck granules in lavaged macrophages
(seen by electron microscopy)

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 Interstitial lung disease associated with BAL eosinophilia

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 (Histiocytosis X)

Sarcoidosis
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Interstitial lung disease associated with BAL neutrophilia

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)

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CD4:CD8 T lymphocyte ratios in diseases presenting with lymphocytic alveolitis

CD4 : CD8 raised

Sarcoidosis
Berylliosis
Asbestosis
Crohn's disease
Rheumatoid arthritis

CD4 : CD8 normal

Tuberculosis
Lymphangioleiomyomatosis

CD4 : CD8 lowered

Hypersensitivity pneumonitis

Silicosis
Drug induced
BOOP
HIV infection
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 LUNG BIOPSY
• Lung biopsy is indicated in patients with:

• atypical or progressive symptoms and signs (fever, weight loss, hemoptysis,

signs of vasculitis),

• atypical radiographic features,

• unexplained extrapulmonary manifestations,

• rapid clinical deterioration, or

• sudden change in radiographic appearance.

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• END

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 Hypersensitivity Pneumonitis (HP)
• HP, or extrinsic allergic alveolitis, is a spectrum of
interstitial, alveolar, and bronchiolar lung diseases
resulting from immunologically induced inflammation
in response to inhalation of a wide variety of different
materials that are usually organic or low–molecular-
weight chemical antigens (or haptens), which may
lead to irreversible lung damage

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 HP…….Introduction
• HP is not an atopic disease and is not associated with increased IgE or eosinophils.

• A large number of agents are associated with HP.

• Prevalence is quite variable in different populations, presumably because of

differing intensity, frequency, and duration of inhalation exposure, and host
factors.

• Farmer's lung is one of the most common forms of HP, affecting 0.4 to 7 percent of
the farming population.

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 HP….. Introduction
• Exposed non smokers tend to develop HP than smokers.

• Exposure explored via occupation or avocational/ recreational is

crucial in the dx of HP.

• Seasonal variation (leading to variation in exposure) is seen.

• 5-10% of HP pts do have asthma.

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 HP….. Introduction
• More than 300 etiologies are reported … the following occupations are seen
commonly ( see table on UTD)
• Farming, vegetable, or dairy cattle workers

• Ventilation and water-related contamination

• Bird and poultry handling

• Veterinary work and animal handling

• Grain and flour processing and loading

• Lumber milling, construction, wood stripping, paper and wallboard manufacture

• Plastic manufacture, painting, electronics industry, other chemicals

• Textile workers
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 HP …. CLINICAL FEATURES
• The manifestations of the disease may be acute, subacute, or chronic.

• This variability likely is because of dose and duration of exposure with

the inciting agent.

• The spectrum is not a continuum.

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 HP …. CLINICAL FEATURES….Acute
HP
• Transient fever, hypoxemia, myalgias, arthralgias, dyspnea, and cough that
occur 2 to 9 hours after exposure and resolve in 12 to 72 hours without specific
treatment (sometimes longer after a particularly intense exposure).

• Patients exhibit tachypnea, bibasilar rales, and occasionally cyanosis.

• There is usually peripheral blood leukocytosis with neutrophilia and

lymphopenia (without eosinophilia), and BAL neutrophilia.

• Elevated acute phase reactants.

• PFT usually reveal a restrictive ventilatory defect during symptomatic episodes.
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 HP …. CLINICAL
FEATURES….Subacute HP
• Subacute or intermittent disease may result from repeated exposures,
and manifest as productive cough, dyspnea, fatigue, and weight loss.

• There may be BAL lymphocytosis, frequently (though not always) with

a predominance of CD8+ T lymphocytes.

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 HP …. CLINICAL FEATURES….Chronic
HP
• The chronic form is clinically more insidious, and patients may lack a history of acute
episodes.

• Present with a gradual onset of cough, dyspnea, fatigue, and weight loss.

• Symptoms are usually present for months to years.

• There is typically no fever, but tachypnea and bibasilar dry rales are usually present.

• Symptoms and signs of cor pulmonale are not uncommon at presentation.

• DDX : IPF and Chronic bronchitis

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 HP…. RADIOGRAPHIC FEATURES…
Acute HP
• In acute HP, chest radiographs demonstrate diffuse poorly defined nodular
radiodensities, often with areas of ground-glass radiodensities or occasionally even
consolidation.

• These radiodensities tend to occur in the lower lobes and spare the apices.

• CT is seldom performed in acute HP because the clinical manifestations are

characteristic and the symptoms usually resolve rapidly.

• The few reported cases demonstrated extensive bilateral ground-glass opacities

(GGOs) with or without dependent areas of consolidation and centrilobular nodules

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 HP…. RADIOGRAPHIC FEATURES…Subacute HP

• The typical finding consists of a heterogeneous appearance of the lung

parenchyma (mosaic attenuation) with patchy or confluent GGOs and
scattered lobular areas of decreased attenuation and vascularity.

• Another common finding is the presence of small centrilobular nodular

opacities of ground-glass attenuation.

• Expiratory HRCT shows air trapping.

• The abnormalities can be diffuse but tend to have lower zone predominance.
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 HP…. RADIOGRAPHIC FEATURES…
Chronic HP
• In chronic HP, CXR are notable for diffuse linear and nodular radiodensities, with sparing of the
bases and upper-lobe predominance, and volume loss.

• HRCT scans of patients with chronic HP demonstrate several patterns. Most commonly there
are multiple centrilobular nodules 2 to 4 mm in diameter throughout the lung
fields ,reticulation accompanied by honeycombing and/or emphysema.

• Unlike sarcoidosis, the nodules are seldom attached to the pleura or bronchovascular bundles,
and the border between the nodules and the surrounding lung is well demarcated.

• There are also well-delineated areas of increased radiolucency, which are presumably
overinflated pulmonary lobules subserved by partly occluded bronchioles.

• Might also resemble IPF.

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 HP…. Diagnosis

exposure

Compatible
Positive
clinical,
inhalation
radiographic, or
challenge
physiologic
testing
HP
findings

Histopathology BAL

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 HP…. MIMICS

• Inhalation fever

• Organic dust toxic syndrome

• Chronic bronchitis

• Airway-centered interstitial fibrosis

• Fire-eater's lung

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 HP….. Rx
• Avoidance, protective equipment and modifying the envt.

• Systemic glucocorticosteroids are usually required to treat severely symptomatic patients.

• The usual treatment is prednisone or prednisolone, 0.5-1m/kg(of ideal body weight) a

day for 2 weeks, followed by a gradual decrease over 2 to 4 weeks.

• !!!!! Maintenance therapy is rarely required.

• ~~~~~~####~~~~~~
• End of HP

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