2. Definition
Heterogenous group of lower respiratory tract disorders
Many potential causes
Common features
Exertional dyspnea, restrictive pattern on PFT, airflow
obstruction, decreased DLCO, increased alveolar-arterial
oxygen difference
absence of pulmonary infection or neoplasm
ILD = misnomer
In pathology, Not restricted to the interstitium
Gas exchange unit + beyond gas exchange unit are
involved
3. Clinical classification
Idiopathic interstitial pneumonias : 40%
IPF(idiopathic pulmonary fibrosis) – m/c, at least 30% of ILD
nonspecific pulmonary fibrosis – 10%
Respiratory bronchiolitis-associated ILD – 6%
Desquamative interstitial pneumonia
ILD associated with collagen vascular disease : RA, SLE, DM, PM, AS
Hypersensitivity pneumonitis : 26%, occupational, environmental
Drug-induced and iatrogenic ILD : cepha., aspirin, amodarone, CBZ
Alveolar filling disorders : DAH, Goodpasture’s, pul. hemosiderosis
ILD associated with pulmonary vasculitis
Wegener’s syndrome, Churg-strauss syndrome
Other specific forms of ILD
sarcoidosis, lymphangioleiomyomatosis, histiocytosis X
Inherited forms of ILD
Neurofibromatosis, tuberous sclerosis
4. Epidemiology
Prevalence in US
Man : 81/100,000
Woman : 61/100,000
Overall incidence in US : man > woman
Man : 31.5/100,000
Woman : 26.1/100,000
6. Clinical manifestations
Progressive dyspnea : typically Sx.
Nonproductive cough, fatigue : common Sx.
Pleuritic chest pain : collagen vascular, drug-induced
Pneumothorax : LAM, neurofibromatosis, Histiocytosis X
Hemoptysis : diffuse alveolar hemorrhagic synd., SLE,
LAM, Wegener, Goodpasture
Coarse rale, crackle in ILD / wheezing is not common
Cyanosis, clubbing
7. Diagnosis : History
Age, sex, smoking
IPF : >50 yrs, 75% smoking
Sarcoidosis : young, middle-aged adult
Langerhans cell histiocytosis : smoking, young man
LAM : women of childbearing age
Respiratory bronchiolitis associated ILD : smoking, all ages
Environmental, occupational factor
Framing, avian antigen, mold, mining, grinding, welding
Medication, drug
Immunosuppression, HIV, transplant
Onset, duration, progression
Extra-pul. Sx.
dysphagia, arthritis, m. weakness, rec. sinusitis, hematuria
8. Diagnosis : Physical examination
Rarely helpful on respiratory exam
Rhonchi, rale, digital clubbing = non-specific
Findings On cardiac exam, in Pts with advanced lung
disease
P2, tricuspid insufficiency, pulmonary hypertension, cor
pulmonale
Extra-thoracic findings
Sarcoidosis : skin abNL, peripheral lymphadenopathy,
hepatosplenomegaly, arthritis
Polymyositis : m. tenderness, proximal m. weakness
Collagen vascular disease : arthritis
9. Diagnosis : Laboratory testing
Not specific : CBC, chemistry panel, U/A
Hypoxemia in moderate to severe ILD
SLE : ANA
RA : RF, anti-citrullinated peptide
Scleroderma : Scl 70
DM, PM : anti-Jo-1, aldolase, creatine kinase
Wegener’s granulomatosis : ANCA
Goodpasture’s syndrome: anti-BM
10. Diagnosis : Chest radiograph
Normal in 10% pts of ILD
Most ILDs
Infiltration in the lower lung zones
No hilar / mediastinal adenopathy
Decreased lung volume
Diffuse GGO -> reticulonodular infiltration
ill-defined nodules w/ air bronchograms
Infiltration : recurrent, migratory
Pleural thickening, pleural effusion, pneumothorax
11. Diagnosis : HRCT
Essential in both the diagnosis and staging of ILD
Earlier diagnosis than CXR
Help narrow differential diagnosis
Aid selecting the site for BAL, lung biopsy
Assist in choosing among therapeutic options
Assist in estimating the response to treatment
12. Diagnosis : Pulmonary function test
Monitoring the progression, prognosis
Restrictive lung defect
Decreased : DLCO, FVC, FEV1, total lung capacity,
lung volume
DDx
Obstructive-restrictive : CSS, allergic bronchopulmonary
aspergillosis, endobronchial sarcoidosis, hypersensitivity
pneumonitis
Respiratory m. weakness : PM, systemic sclerosis, SLE
13. Diagnosis : Exercise testing
Increased PAO2-PaO2 ∝ severity of disease, degree
of fibrosis
Decreased work rate, maximal oxygen consumption
Abnormally high minute ventilation
Decreased peak minute ventilation
Failure of tidal volumes to increase
6-min walk test : quantitative date on exercise
capacity and oxygen desaturation with exercise
14. Diagnosis : Invasive evaluation
Bronchoalveolar lavage
Lymphocyte, eosinophil, asbestos body, staining
surfactants
Transbronchial lung biopsy
Non-caseating granuloma, giant cell, smooth m.
proliferation
Video-assisted thoracoscopic biopsy
Open lung biopsy
Most IPF do not need to have biopsy to confirm the
diagnosis
15. Treatment
Avoidance of the inciting agent
Systemic corticosteroid
Unclear dosage and duration
Supportive oxygen supplementation
Treatments for pulmonary hypertension
Lung transplantation
End-stage ILD : significant pul. Fibrosis, pul. Hypertension
21. Treatment
2014-07-1121
No treatment to improve survival rate
All treatments are experimental
Oral prednisone + azathioprine + N-acetylcysteine
Better preservation of PFT
Pirfenidone + anti-fibrotic agent
Loss of lung function↓, progression-free survival↑
Empirical IV corticosteroid
Not beneficial
INF-ɣ1b , cyclophosphamide, colchicine, D-penicillamine, oral
corticosteroid + immunosuppressive agent
Supplemental O2, Tx of infection, PE, pul. HTN, GERD
Immunization for influenza, herpes zoster, pneumococcus
Lung transplantation : 2/3 of IPF is a contraindication
22. Prognosis
2014-07-1122
Progressive impairment of lung function, gas exchange
Median survival : 3~5 yrs
Longer survival
Less fibrosis, less functional impairment, no pul. HTN,
no significant oxygen desaturation on the 6min walk test
Shorter survival
Emphysema, pul. HTN, acute exacerbation
23. Nonspecific Interstitial Pneumonia
2014-07-1123
Two subgroup : cellular, fibrotic
Fibrotic NIP is similar to early IPF
Onset age : 50 yrs
Diagnosis
CXR : bilateral patchy infiltration in LLF
HRCT
Cellular : bilateral GGO, consolidation, subpleural reticulation, loss
of lower lobe volume
Fibrotic : bilateral architectural derangement in lower lobe
Bx.
Cellular : chronic lymphoplasmacytic infiltration
Fibrotic : dense interstitial fibrosis
Treatment : corticosteroid
Prognosis : better than IPF
38. Progressive systemic sclerosis
2014-07-1138
most frequently associated with ILD
nonspecific interstitial pneumonia
Clinical manifestation
Pulmonary Sx → cutaneous or digital Sx
chronic pulmonary fibrosis : bronchogenic ca. ↑
Tx
cyclophosphamide for 1 year
39. Rheumatoid arthritis
2014-07-1139
more common in men (3:1 ratio) at 50th to 60th
Clinical manifestation
bronchiectasis, bronchiolitis,
idiopathic interstitial pneumonias
pleural effusions or pleural thickening
lymphocytic infiltrate ↑ -> fibrous tissue, honeycomb
Tx
underlying RA
40. Systemic lupus erythematosus
2014-07-1140
Pleural disease (m/c) or pleural effusions
widespread GGO w/ consolidation, or DAH
Shrinking lung
Result of diaphragmatic weakness→Progressive lung
restriction →resistant to Tx
Tx
underlying SLE
41. Dermatomyositis and Polymyositis
2014-07-1141
anti-Jo-1 antibody
Clinical manifestation
acute interstitial pneumonia–like syndrome
ILD → muscular manifestations
The severity of the muscular dis. does not corr. with ILD
Tx
underlying DM PM
42. Sjogren’s syndrome
2014-07-1142
ILD is primary form
Lymphocytic interstitial pneumonia
Respiratory infections & bronchiectasis
common in advanced stages
Tx response is usually good
43. Mixed connective tissue disease
2014-07-1143
overlap syndrome
Pulmonary disease is common
but most often subclinical & identified only radiographically
Tx
underlying disease
46. Hypersensitivity Pneumonitis
2014-07-1146
extrinsic allergic alveolitis
Pathogenesis
repeated inhalation of specific antigens
inflammatory cell infiltration : bronchioles, alveoli & interstitium
noncaseating, epithelioid cell granulomas
A history of exposure is essential to Diagnosis & Tx
47. 2014-07-1147
Diagnosis
CXR : focal patchy consolidation or diffuse GGO
→ micronodular & reticular shadowing
→ upper lung zone reticulation with honeycombing
BAL : lymphocytes & plasma cells ↑↑
HRCT : small centrilobular ill-defined nodules of GGO
Biopsy : granulation ↑↑ (small airways & alveolar ducts)
& chronic inflammation in the surrounding alveoli
Tx & Px
avoidance of exposure to the antigen
Corticosteroids
Continued exposure : chronic HP & irreversible fibrosis
48. Occupational ILDs
2014-07-1148
silicosis inhalation of silica in crystalline form
or silicon dioxide,
sandblasting & working w/ granite
coal workers’
pneumoconiosis
inhalation of coal dust
asbestosis deposition of fibers
during mining, milling
welding & working in a shipyard
berylliosis seen in aerospace workers
& in electronic industries
58. PULMONARY LANGERHANS CELL
HISTIOCYTOSIS
2014-07-1158
pulmonary histiocytosis X or eosinophilic granuloma of the lung,
idiopathic, granulomatous ILD 20 ~ 30th, male, smoke
DIAGNOSIS
CXR : diffuse symmetrical reticulonodular opacities + multiple small cysts (upper &
mid lung)
HRCT : subpleural nodules, scattered GGO, irregular cysts in both lungs, with
spare lung bases
PFTs : a mixed restrictive & obstructive pattern
BAL : Langerhans cells (atypical histiocytes)
TBLB. Open lung bx
interstitial and peribronchiolar (histiocytes, eosinophils, and lymphocytes)
peribronchiolar nodules + cysts + central stellate fibrosis.
immunostaining : CD1, S-100
Tx & Px
prognosis is favorable
discontinue smoking (75% of patients improving or stabilizing)
corticosteroids
w/ or w/o vincristine, cyclosporine, cyclophosphamide, azathioprine
59. LYMPHANGIOLEIOMYOMATOSIS
2014-07-1159
Women>men, childbearing age.
Sx
Hemoptysis, pneumothorax(rupture of subpleural cysts) chylothorax (lymphatic ob.)
CXR: Coarse reticulonodular infiltrates, often w/ bilat’ cysts or bullae, lung vol. ↑
HRCT : diffuse thin-walled cysts <2 cm
BAL : occult alveolar hemorrhage
Lung bx : abNL sm. cells in airways, lymphatics, bv,
w/ concurrent airflow obstruction & replace parenchyma with cysts
Tx & Px
Sirolimus(RCT) progesterone or Tamoxifen(non-RCT)
10 yrs survival after the onset of symptoms
60. Inherited Disorders
2014-07-1160
AD tuberous sclerosis indistinguishable from LAM
both radiographically & histopathologically
neurofibromatosis bilateral lower lobe fibrosis
& bullae or cystic changes
AR Gaucher’s disease interstitial infiltration
w/ fibrosis, alveolar consolidation,
& filling of alveolar spaces
Niemann-Pick disease infiltration of the characteristic "foam cell"
throughout the pulmonary lymphatics,
the pulmonary arteries,
& the pulmonary alveoli
Hermansky-Pudlak
syndrome
Pulmonary fibrosis;
onset in the 30th~ 40th
slowly progressive