Interstitial Lung Disease

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실습 2조 강천지, 구윤수

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

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

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

Pathobiology

Unknown tissue injury + attempted repair

Fibroproliferattion ⇒ honeycombing

⇒ pulmonary vascular resistance↑ + 2nd pulmonary HTN

Highly heterogeneous findings

Normal, inflammation, fibrosis, granuloma, vasculitis,

secondary vascular change

Gene : hTERT, hTR(telomerase), MUC5B promotor

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

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

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, corpulmonale

Extra-thoracic findings

Sarcoidosis : skin abNL, peripheral lymphadenopathy, hepatosplenomegaly, arthritis

Polymyositis : m. tenderness, proximal m. weakness

Collagen vascular disease : arthritis

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

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

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

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

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

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

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

2014-07-1116

Idiopathic Interstitial Pneumonias

Idiopathic pulmonary fibrosis

Nonspecific interstitial pneumonia

Respiratory bronchiolitis-associated ILD

Desquamative interstitial pneumonia

Acute interstitial pneumonia

Cryptogenic organizing pneumonia

Lymphoid and lymphocytic interstitial pneumonia

Idiopathic Interstitial Pneumonias

Unknown etiology

Dyspnea, nonproductive cough, chest pain, wt. loss,

fatigue, crackle, clubbing

HRCT, better than CXR

Idiopathic Pulmonary Fibrosis

2014-07-1118

Epidemiology

50~60% of IIP

Mean age at onset : 62 yrs(older than 50 yrs)

Clinical manifestation

Cigarette smoking, coexisting emphysema

Gradual dyspnea, restrictive pattern on PFT

HRCT : bilateral pulmonary fibrosis

Median survival : 3~5 yrs after diagnosis

Acute exacerbation : 5~10%, admission & ICU

Diagnosis

2014-07-1119

CXR : basal, reticular pattern, decreased lung volume

HRCT

basilar patchy intra-lobular reticulation

Subpleural honeycomb cysts

Traction bronchiectasis : advanced disease

PFT : restrictive pattern

Mild disease : normal lung volume, small decreased DLCO,

normal PFT

BAL : nonspecific / neutrophil, eosinophil

Histopathology : honeycombing, fibrosis, inflammatory

cell, collagen deposition, normal lung

Diagnosis

2014-07-1120

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

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

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

RESPIRATORY BRONCHIOLITIS–

ASSOCIATED ILD

2014-07-1124

Epidemiology : Smoking, 40th or 50th yrs

Diagnosis

PFTs

airway obstruction, mildly decreased or preserved TLC, Dlco ↓

CXR

bronchial wall thickening, GGO

BAL

brown-pigmented alveolar macrophages w/ neutrophils

HRCT

Biopsy

Diagnosis

2014-07-1125

Treatment and Prognosis

2014-07-1126

cessation of smoking

low-dose corticosteroids

(e.g., prednisone, 10 to 20 mg/day) for a few months

DESQUAMATIVE INTERSTITIAL

PNEUMONIA

2014-07-1127

more extensive form of RB-ILD

More affected in smoker

Diagnosis

PFTs

restrictive pattern, Dlco ↓ w/ or w/o obstruction

CXR

patchy basal consolidation w/ a lower lobe & periphery

BAL

pigmented alveolar Mø, frequently w/ neutrophils ↑

HRCT

Biopsy

Diagnosis

2014-07-1128

Treatment and Prognosis

2014-07-1129

cessation of smoking

oral corticosteroid therapy

lung transplantation for selected patients

Good therapeutic outcome, survival rate : 70% at 10 yrs

Treatment and Prognosis

2014-07-1130

Treatment and Prognosis

2014-07-1131

ACUTE INTERSTITIAL PNEUMONIA

2014-07-1132

Healthy person

after viral URI

mimics the ARDS

Dx

CT scan

CRYPTOGENIC ORGANIZING

PNEUMONIA (idiopathic BOOP)

2014-07-1133

flulike illness w/ nonproductive cough, followed by exertional dyspnea

DX

PFTs : restrictive defect

CXR : peripheral or recurrent migratory alveolar opacities

BAL : nonspecific

HRCT

LLF consolidation(subpleural or peribronchial),

small nodules along bronchovascular bundles & GGO

Biopsy : granulation tissue ↑↑

within the small airways & alveolar ducts

Treatment and Prognosis

2014-07-1134

oral corticosteroids

adjunct immunosuppressive agents (azathioprine)

Spontaneous remissions can occur

LYMPHOID AND LYMPHOCYTIC

INTERSTITIAL PNEUMONIA

2014-07-1135

Epidemiology

women > men, especially in the 50th

Clinical manifestation

Concurrent collagen vascular dz. or an autoimmune dis (esp. Sjogren’s synd.)

gradual onset of cough & exertional dyspnea

Dx

CXR : Lower lung field reticular or reticulonodular pattern

BAL : lymphocytes ↑

HRCT : bilateral GGO, small or large nodules & scattered cysts

perivascular honeycombing & reticular abnormalities

Biopsy : dense interstitial lymphocytic infiltrate

Treatment and Prognosis

2014-07-1136

oral corticosteroids

more than 1/3 of pts progressing to diffuse pul. fibrosis

ILD Associated with

Collagen Vascular Disease

2014-07-1137

Progressive systemic sclerosis

Rheumatoid arthritis

Systemic lupus erythematosus

Dermatomyositis and polymyositis

Sjogren’s syndrome

Mixed connective tissue disease

Ankylosing spondylitis

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

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

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

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

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

Mixed connective tissue disease

2014-07-1143

overlap syndrome

Pulmonary disease is common

but most often subclinical & identified only radiographically

Tx

underlying disease

Ankylosing spondylitis

2014-07-1144

upper lobe, bilateral reticulonodular infiltrates

w/ cyst formation

Tx : no known effective therapy

for apical fibrobullous disease

Hypersensitivity Pneumonitis

2014-07-1145

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

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

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

Drug-Induced ILD

2014-07-1149

alveolar and interstitial abnormalities

granulomatous pneumonitis

chronic nitrofurantoin-induced ILD

Drug-Induced ILD

2014-07-1150

Nonspecific bilateral

alveolar & interstitial

inflammatory

& fibrotic abnormalities

sarcoid-like

granulomatous ILD

Alveolar Filling Disorders

2014-07-1151

IDIOPATHIC PULMONARY HEMOSIDEROSIS

CHRONIC EOSINOPHILIC PNEUMONIA

IDIOPATHIC PULMONARY

HEMOSIDEROSIS

2014-07-1152

Epidemiology

children and young adults : rare

DAH w/o vasculitis, inflammation, granulomas, necrosis

Dx

BAL : Hemosiderin-laden macrophages

CXR

diffuse, bilateral alveolar infiltrates

hilar & mediastinal adenopathy

Tx

Systemic corticosteroids

CHRONIC EOSINOPHILIC PNEUMONIA

2014-07-1153

20th ~ 40th women, Peripheral blood eosinophilia : common, usually 10 to 40%

Sx

fevers, sweats, weight loss, fatigue, dyspnea, cough

Cardinal feature

CXR & HRCT : peripheral multifocal consolidation

predominantly in the upper and mid lung zones

BAL : eosinophils > 40% during exacerbations

Dx & Tx: corticosteroids

“photographic negative of pulmonary edema,”

Px: Relapse rate is high

ILD associated

with Pulmonary Vasculitides

2014-07-1154

WEGENER’S GRANULOMATOSIS

CHURG-STRAUSS SYNDROME

IDIOPATHIC PULMONARY CAPILLARITIS

ILD associated

with Pulmonary Vasculitides

2014-07-1155

WEGENER’S

GRANULOMATOSIS

CHURG-STRAUSS

SYNDROME

IDIOPATHIC

PULMONARY

CAPILLARITIS

m/c form of vasculitis

Destruction of the

nasal cartilage

→ septal perforation

→ cavitating nodules

Vasculitis of both

respiratory tracts

allergic disorders,

eosinophilia, IgE ↑

bronchospasm

pulmonary vasculature

within the alveolar walls

Manifestation like ILD

CXR multiple nodular or

cavitating infiltrates

bilateral patchy,

diffuse nodular

infiltrates, diffuse

reticulonodular dis.

Dx: ACNA Histopathologic

examination

subclinical alveolar

hemorrhage associated

w/ p- ACNA

Tx cyclophosphamide

→ Rituximab

corticosteroid unclear

Corticosteroids

cyclophosphamide

or rituximab

Other Forms of ILD

2014-07-1156

SARCOIDOSIS

PULMONARY LANGERHANS CELL HISTIOCYTOSIS

LYMPHANGIOLEIOMYOMATOSIS

SARCOIDOSIS

2014-07-1157

Idiopathic chronic multi- system granulomatous dis.

Epidemiology : 20~ 40th , women

Pathogenesis

T helper 1 cell ↑↑ → non caseating granuloma

Clinincal manifestation : Lung, Liver, skin, eye

Lung : ILD, BHL

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

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

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

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