Interstitial Lung Disease <14판>

1. 정의 및 개요

alveolar wall(septa), perialveolar tissue, supporting structure를 침범하는 여러가지 상황들

을 통칭함. nonmalignant, noninfectious, insidious onset, chronic duration

epithelial cell injury -> air space, alveolar wall inflammation

-> intraluminal & mural alveolitis(acute phase)

-> interstitial fibrosis(chronic phase)

inflammation은 conducting airway를 침범할수도 있다.

지금은 BOOP이 ILD의 한 spectrum으로 여겨진다.

2. 분류

known cause vs unknown cause의 2 groups으로 나누는데

각각 granuloma유무에 따라 subgroups으로 나눈다.

ILD가운데 큰 부분을 차지하는 것이 occupational & environmental inhalant exposure

(inorganic dust or noxious gases)이다.

unknown cause부분 또한 큰데 IPF, sarcoidosis, ILD associated with collagen vascular

disease등이 있다.

*Tab 259-1

Lung response : alveolitis, interstitial inflammation, fibrosis

1)known cause

Asbestos, Fumes, Gas, 항생제, 방사선, Aspiration pneumonia

drug(antibiotics, amiodarone, gold, chemotherapeutic drugs)

2)unknown cause

IPF(UIP), collagen vascular disease(SLE등), pulmonary hemorrhagic syndrome

(Goodpasture's syndrome, idiopathic pulmonary hemosiderosis),

Pulmonary alveolar proteinosis, Eosinophilic pneumonia, Amyloidosis

Lung response : as above but with Granuloma

1)known cause

Hypersensitivity pneumonitis(organic dust)

Inorganic dust : beryllium, silica

2)unknown cause

Sarcoidosis, Eosinophilic granuloma

Granulomatous vasculitides : Wegener's granulomatosis, Allergic granulomatosis of

Churg-Strauss

Idiopathic pulmonary fibrosis(IPF) = Cryptogenic fibrosing alveolitis

: nonproductive cough, progressive dyspnea

CXR상 lower lung reticular or reticulonodular shadow

PFT상 restrictive pattern을 보인다.

1. Immunopathogenesis

* alveolar wall은 type I pneumocyte, type II pneumocyte, mesenchymal cell,

(fibroblast,macrophase등), collagen, adhesive proteoglycan 등으로 이루어져 있다.

* upper or conducting airway는 침범하지 않으나 resp. bronchioles의 bronchiolitis는

일으킬수 있으며 alveolar unit를 흔히 침범한다.

* 초기 - reversible form of alveolar injury

( alveolar & interstitial edema, intraalveolar hyaline membrane formation)

진행되면 - macrophage에 의해 chemokine분비 -> mesenchymal cell자극

-> fibroblast증식

( Fig 259-1 )

2. 임상적 특징

1) Hx : exertional dyspnea, effort intolerance, dry cough

fatigue, anorexia, wt loss, arthralgia동반

2) P/E : 초기는 정상

말기엔 cor pulmonale발생, pul hypertension(P2 sound↑), Rt sided heart failure,

RVEF↓

3) Lab & diagnostic test

① Imaging study

* CXR : diffuse reticular or reticulonodular marking - lower lung

early- hazy "ground glass" appearance of the lower lung field - acute alveolar stage

later- nodular infiltration

end-stage - all lung field linear opacity, cystic & bronchiectatic change(=

honey-combed appearance)

* HRCT : disease activity monitor에 도움

* Bx-proven diffuse IPF중 CXR가 정상인 경우가 있다(14%).

② Lab : ESR↑, circulating immune complex titer, immunoglobulin↑

③ PFT

④ Bronchoscopy

4-6 transbronchial biopsy시행 -> definite pathologic diagnosis를 얻는경우가 1/4.

sarcoidosis와 같은 diffuse granulomatous interstitial disease는

transbronchial biopsy만으로 조직진단에 충분하다(80%).

⑤ Lung biopsy

transbronchial Bx로 진단에 필요한 충분한 조직을 얻을수 없다면

thoracoscopy-guided or open lung biopsy를 고려해야 한다.

4) Diagnostic approach & staging

① occupational & environmental Hx가 중요

② aspiration & infection : DDx에 중요

③ CXR or HRCT, PFT, ABGA를 측정한다.

④ 진단전에 조직학적 분석이 필요하다.

FOB : first invasive procedure

infection, malignancy, 다른 특정질환을 배제하는데 중요

⑤ BAL : alveolar inflammation & immunologic activity를 판단하는데 유용하다.

⑥ 67 Ga lung scan : 진단적 정확성 혹은 activity를 monitoring하는데 더 이상 도움이

안된다.

⑦ bronchoscopy로 진단이 의심스러우면 thoracoscopic or open lung bipsy를 고려한다.

3. 치료

1) oral Pd : 1mg/kg/d X 8주

response(+) -> 0.25 mg/kg/d X 6개월

response(-) -> immunosuppression(cyclophosphamide)

1.0mg/kg/d(total 50-75mg) + oral Pd(0.25mg/kg/d)

7-10일 간격으로 50mg씩 증량

WBC는 대략 1/2로 감소되는 것을 목표로, 1000개 미만일때는 stop.

2) high-dose, pulsed glucocorticoid : special advantage(-)

3) Azathioprine : cyclophosphamide 대신 사용

4) colchine : macrophage-produced fibroblast growth factor억제. 0.6mg/d

5) stop cigarette smoking

6) diuretics : Rt-sided CHF때

7) prophylaxis of pneumococcal & influenza vaccine

8) lung transplantation고려

Individual forms of ILD

1. Collagen vascular disorders

1) SLE : 1/2에서 결국 over lung disese로 진행한다.

mc : pleuritis, pleural effusion, acute pneumonitis

chronic, progressive ILD : uncommon

2) RA : pleural disease(pleural effusion & subpleural nodules)

parenchymal nodular infiltrates

diffuse interstitial fibrosis

BOOP이 보고됨

MTX, gold치료시 ILD로 발전할 가능성(drug hypersensitivity)이 있는데

이때 preexisting or developing ILD)와 감별해야 한다.

Penicillamine Tx : bronchiolitis obliterans의 원인이 됨.

3) Ankylosing spondylititis : bilateral upper lobe fibrosis, fibrocavitary ds합병가능

4) systemic sclerosis

5) sjogren's syndrome

6) polymyositis & dermatomyositis(5-10%): anti-Jo-1 Ab가 있는 환자에서 더 흔히 발생

2. Pul. hemorrhage

1) Goodpasture's syndrome

2) Idiopathic pulmonary hemosiderosis

3. Pulmonary alveolar proteinosis

diffuse alveolar consolidation and/or nodular shadows

typically radiating from the hilar regions

alveoli - PAS(+) granular materials로 차있다.

no inflammation & normal septal structure

intraalveolar material : surfactant phospholipid, LDH, other protein, Ig의 복합체

4. Lymphocytic infiltrative disorders

5. Eosinophilic pneumonia

많은 약들이 eosinophilc pneumonia를 유발한다. 주로 older female

lung Bx로 진단 => eosinophilic inflammatory process

6. Lymphangioleiomyomatosis

7. Amyloidosis

8. Inherited disorders

9. GI & liver disease

10. GVHD

11. Granulomatous response

1) Langerhans cell granulomatosis(Eosinophilic granuloma or Histiocytosis X)

unknown etiology의 ILD의 1-5%

* dendritic cell : potent stimulatory & accessory cell immune function

interstitium, alveolar septal area & BAL fluid에서 발견

tissue macrophage와는 확연히 다름.

BAL cell에서 3%이상 인지(other disease보다 많은 수치임)

그러나 Langerhans cell은 not pathognomonic

CXR : diffuse micronodular shadows & cystic spaces, CPA sparing

PFT : obstructive & restrictive defect이 공존

병이 진행될수록 advanced COPD와 비슷

* 치료

① stop smoking

② glucocorticoid : not helpful

③ penicillamine : prevent fibrosis

④ local bone lesion : irradiation

⑤ supportive Tx & bronchodilator : 효과는 중등도

⑥ lung transplantation : 일부환자에서 고려

2) Granulomatous vasculitis

Wegener's granulomatosis

Churg & Strauss granulomatosis: asthma, eosinophilia가 존재

3) Lymphomatoid granulomatosis

lung에 일차적으로 침범하고, skin, CNS, PNS, kidney에는 덜 흔하다.

50%에서 malignant lymphoma로 진행한다.

치료 : glucocorticoid, cyclophosphamide

12. Bronchocentric granulomatosis