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Interstitial Lung Diseases (ILD)Interstitial Lung Diseases (ILD)Diffuse Parenchymal Lung Diffuse Parenchymal Lung

Diseases (DPLD)Diseases (DPLD)Edit Csada, MDEdit Csada, MD

29.10.2014.29.10.2014.

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Interstitial lung disorders Interstitial lung disorders (ILD)(ILD)

The interstitial lung disorders are The interstitial lung disorders are chronic, nonmalignant, chronic, nonmalignant, noninfectious diseases of the lower noninfectious diseases of the lower respiratory tract characterized by respiratory tract characterized by inflammation and derangement of inflammation and derangement of the alveolar walls.the alveolar walls.

Secondary fibrosis and pulmonal Secondary fibrosis and pulmonal hypertension may develophypertension may develop

Prevalence: 7-20/100 000Prevalence: 7-20/100 0002

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Etiology (ATS/ERS 2002)

1. Known origin Drugs (busulfan,

nitrofurantoin, bleom., amiodaron)

Pneumoconiosis Connective tissue

diseases Irradiation Malignant diffuse

infiltr. lung diseases

2. Granulomatous origin

Sarcoidosis Hypersensitive

pneumonitis

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Etiology

3. Other DPLD Langerhans-cell

histiocytosis Lymphangioleiomyo

matosis Alveolar proteinosis Wegener

granulomatosis

4. IIP UIP (IPF) DIP/RBILD NSIP AIP COP LIP

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According to the pathogenesis I.

Acute DPLD allergy (drugs) toxin (gas) vasculitis/hemorrhage (Goodpasture,

idiopathic hemosiderosis) ARDS (trauma, septicaemia) unknown (COP, BOOP)

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According to the pathogenesis II.

Episodic DPLD eo pneumonia vasculitis, hemorrhage Churg-Strauss sy Hypersensitive pneumonitis COP

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According to the pathogenesis III.

Chronic DPLD (exposition)

inorganic dusts (silicosis, asbestosis) organic dusts (bacteria, fungi, animal

proteins) drugs

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According to the pathogenesis IV.

Chronic DPLD (systemic diseases) sarcoidosis connective tissue diseases malignant diseases (lymphoma, lymphangitis cc) vasculitis (Wegener) hereditary diseases others ( bone marrow transplantation,

inflammatory intestine diseases, amyloidosis)

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According to the pathogenesis V.

Chronic DPLD (without systemic disease and without exposition)

Idiopathic interstitial pneumonitis (IIP) alveolar proteinosis chronic aspiration LAM Langerhans-cell histiocytosis venoocclusive disease idiopathic pulmonal haemosiderosis bronchioloalveolar cc.

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Morphologic changesMorphologic changes

Loss of pulmonary capillariesLoss of pulmonary capillaries Alterations of alveolar epithelial cellsAlterations of alveolar epithelial cells Fibrosis of alveolar wallsFibrosis of alveolar walls

PathogenesisPathogenesis

Total number of inflammatory cells increasesTotal number of inflammatory cells increases The proportions of inflammatory cells changeThe proportions of inflammatory cells change The inflammatory cells are activatedThe inflammatory cells are activated

Mediators release – toxic oxygen radical, proteasesMediators release – toxic oxygen radical, proteases FibrosisFibrosis Impairment of O2 transportImpairment of O2 transport

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Normal cell content of BALNormal cell content of BAL

90%90% alveolar macrophagesalveolar macrophages 7%7% lymphocyteslymphocytes 1%1% polymorph leucocytespolymorph leucocytes

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•Neutrophyl alveolitis : cryptogenic fibrotic alveolitis

•Lymfocytic alveolitis : sarcoidosis, hypersensitive pneumonitis, beryllosis

•Eosinophil alveolitis

•Mixed-cell alveolitis: amiodaron fibrosis (eosinophil+lymphocyte)

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Clinical features in ILD I.Clinical features in ILD I.

SymptomsSymptoms Dyspnea during exerciseDyspnea during exercise FatigueFatigue Nonproductive coughNonproductive cough

Physical findingPhysical finding Dry, crackling ralesDry, crackling rales WheezingWheezing Tubular breath soundsTubular breath sounds Digital clubbingDigital clubbing

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Clinical features in ILD II.Clinical features in ILD II.

Laboratory changesLaboratory changes ERS can be elevatedERS can be elevated HypoxaemiaHypoxaemia

Chest X-ray, HRCT scanChest X-ray, HRCT scan ReticularReticular NodularNodular ReticulonodularReticulonodular Ground glass hazinessGround glass haziness HoneycombingHoneycombing

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Clinical features in ILD III.Clinical features in ILD III. Lung function testsLung function tests

Reduction in VC, TLCReduction in VC, TLC FEV1/FVC is normal, or supranormalFEV1/FVC is normal, or supranormal Decrease in diffusing capacity, transfer factorDecrease in diffusing capacity, transfer factor

(DLCO)(DLCO) Oxyergospirometry (exercise test)Oxyergospirometry (exercise test)

Scintigraphic findings Tc99, Xe133Scintigraphic findings Tc99, Xe133 Patchy abnormalitiesPatchy abnormalities

BALBAL Various mixtures of inflammatory cellsVarious mixtures of inflammatory cells

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Diagnosis of ILDDiagnosis of ILD

Clinical featuresClinical features Transbronchial biopsyTransbronchial biopsy VATSVATS Open lung biopsyOpen lung biopsy

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Therapy of ILDTherapy of ILD Known etiologyKnown etiology

Remove the individual from exposure to the Remove the individual from exposure to the causative agentscausative agents

Known and unknown etiologyKnown and unknown etiology Suppress inflammatory processSuppress inflammatory process

Oral corticosteroids (1mg/kgOral corticosteroids (1mg/kg0,25 mg/kg)0,25 mg/kg) CPA (cyclophosphamide)CPA (cyclophosphamide) Imuran (azathioprine)Imuran (azathioprine)

Late stageLate stage O2 therapyO2 therapy Supportive treatmentSupportive treatment TransplantationTransplantation

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Idioptahic pulmonary fibrosis Idioptahic pulmonary fibrosis (IPF)(IPF)

Hamman-Rich sy (acute IP)Hamman-Rich sy (acute IP) Cryptogenic fibrosing alveolitis (COP)Cryptogenic fibrosing alveolitis (COP) Desquamative intersitial pneumonitis Desquamative intersitial pneumonitis

(DIP)(DIP) Usual interstitial pneumonitis (UIP)Usual interstitial pneumonitis (UIP) Respiratory bronchiolytis-associted IP Respiratory bronchiolytis-associted IP

(RB-ILD)(RB-ILD) Nonspecific interstitial pneumonitis Nonspecific interstitial pneumonitis

(NSIP)(NSIP) Lymphoid interstitial pneumonitis (LIP)Lymphoid interstitial pneumonitis (LIP)

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Idioptahic pulmonary fibrosis Idioptahic pulmonary fibrosis (IPF)(IPF)

The cause of condition is not clear.The cause of condition is not clear. Chr. inflammatory process initiated Chr. inflammatory process initiated

by immune complexesby immune complexes derangement of the lung derangement of the lung

parenchymaparenchyma The clinical features are similar to The clinical features are similar to

other ILDother ILD

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Radiologic changes of IPFRadiologic changes of IPF

Ground glass hazinessGround glass haziness Streaky wisps of shadowStreaky wisps of shadow Generalized micronodular mottlingGeneralized micronodular mottling Honeycomb lungHoneycomb lung

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Diagnosis of IPFDiagnosis of IPF

Clinical featuresClinical features X-rayX-ray CT scanCT scan Diffusing capacity, transfer factor Diffusing capacity, transfer factor

decreaseddecreased (DLCO) (DLCO) BAL (neutr.)BAL (neutr.) Transbronchial biopsyTransbronchial biopsy VATSVATS Open lung biopsyOpen lung biopsy

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ATS/ERS ATS/ERS diagnostic criteria of IPF diagnostic criteria of IPF (biopsy)(biopsy)

Major Major criteriacriteria There is no known cause of ILD (drug, There is no known cause of ILD (drug,

environmental exposition) environmental exposition) Impaired lung function, restriction, decreased Impaired lung function, restriction, decreased

diffusion capacitydiffusion capacity Bilateral basal reticular, streaky shadow, Bilateral basal reticular, streaky shadow,

minimal granulomas minimal granulomas There is no other diseases with similar There is no other diseases with similar

symptomssymptoms Minor Minor criteriacriteria

AgeAge > 50 > 50 There is no other cause of dyspnoeThere is no other cause of dyspnoe Duration of diseaseDuration of disease > 3 > 3 monthmonth Bilateral basal subcrepitatioBilateral basal subcrepitatio AJRCCMAJRCCM

2002;165:277-3042002;165:277-304

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Therapy of IPF (ATS) No treatment

Age > 70 years Extreme obesity DM, hearth disease, osteoporosis Severe impaired lung function Honeycomb lung

Early and combined treatment CS+ azathioprine CS+ cyclophosphamide CS+ azathioprine+ N-acetylcysteine

Restaging after 3-6-9-12-18 month Symptoms, radiology, lung function, side effects

PR, transplantation Best supportive care, O2 treatment

Therapy of IPF (ATS)

New drugsNew drugs InterferonInterferon BosentanBosentan EtanerceptEtanercept PirfenidonPirfenidon

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Sarcoidosis (Morbus Boeck)Sarcoidosis (Morbus Boeck)

It is clinically well defined, systemic, It is clinically well defined, systemic, granulomatous disease of unknown granulomatous disease of unknown origin.origin.

HistologyHistology Altered immuneAltered immune

responseresponse

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Clinical features of sarcoidosisClinical features of sarcoidosis

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Radiological appearances of Radiological appearances of sarcoidosissarcoidosis

Stage/form IStage/form I BHL syBHL sy Stage/form IIStage/form II pulmonary pulmonary

dissemination dissemination with with or without BHLor without BHL

Stage/form IIIStage/form III pulmonary fibrosispulmonary fibrosis

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Diagnosis of sarcoidosisDiagnosis of sarcoidosis BHL accompanied by erythema nodosum BHL accompanied by erythema nodosum

(Löfgren-sy)(Löfgren-sy) Tuberculin test: negativeTuberculin test: negative Lung function testsLung function tests Se ACE (angiotensin converting enzyme) Se ACE (angiotensin converting enzyme)

increasesincreases Transbronchial biopsy, perbronchial biopsy Transbronchial biopsy, perbronchial biopsy

(TBNA)(TBNA) BAL (ly)BAL (ly) Gallium scanGallium scan MediastinoscopyMediastinoscopy

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Treatment of sarcoidosisTreatment of sarcoidosis

Stage I:Stage I: no treatment is necessaryno treatment is necessary Indication of steroid treatment:Indication of steroid treatment:

Progressive pulmonary diseaseProgressive pulmonary disease Severe uveitisSevere uveitis HypercalcaemiaHypercalcaemia Neurological involvementNeurological involvement

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Histiocytosis X (Langerhans)Histiocytosis X (Langerhans) This is a disorder of the mononuclear This is a disorder of the mononuclear

phagocyte system characterized by the phagocyte system characterized by the accumulation of mononuclear phagocytes accumulation of mononuclear phagocytes is various organs.is various organs.

In pediatric patientsIn pediatric patients Letterer-Siwe diseaseLetterer-Siwe disease Hand-Schüller-Christian diseaseHand-Schüller-Christian disease

In adultsIn adults Histiocytosis XHistiocytosis X Eosinophilic granulomaEosinophilic granuloma

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Clinical features of Clinical features of histiocytosisXhistiocytosisX

20-40 years of age (smoking)20-40 years of age (smoking) Nonproductive coughNonproductive cough DyspneaDyspnea Chest painChest pain Ptx – 10% of all casesPtx – 10% of all cases

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Characteristics of Characteristics of histiocytosisXhistiocytosisX X-ray changesX-ray changes

Reticulonodular shadowReticulonodular shadow Small cystic spacesSmall cystic spaces

Lung function testsLung function tests Mixed restrictive-obstructive patternMixed restrictive-obstructive pattern Decreased diffusing capacityDecreased diffusing capacity

BALBAL Large number of mononuclear phagocytesLarge number of mononuclear phagocytes

HistologyHistology X bodies (Birbeck) in the cytoplasmX bodies (Birbeck) in the cytoplasm

There is no known treatment. Corticosteroids may There is no known treatment. Corticosteroids may be given.be given.

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Langerhans-cell histiocytosis

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Rheumatoid arthritisRheumatoid arthritis

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TreatmentTreatmentIf the disease is mild, no specific If the disease is mild, no specific therapy is used.therapy is used.If the ILD is progressive, corticosteroids If the ILD is progressive, corticosteroids are administered.are administered.

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Other immunological Other immunological disesesdiseses

SLESLE Sjögren sySjögren sy SclerodermaScleroderma BechterewBechterew Dematomyositis, polymiositisDematomyositis, polymiositis Periarteritis nodosaPeriarteritis nodosa NeurofibromatosisNeurofibromatosis

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Alveolar proteinosisAlveolar proteinosis

Primary-secondary (myeloid Primary-secondary (myeloid leukaemy, dust)leukaemy, dust)

PAS positive lipoproteinPAS positive lipoprotein X-ray: butterfly shape infiltrationX-ray: butterfly shape infiltration Therapy: BALTherapy: BAL

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Eosinophylic pneumoniasEosinophylic pneumonias

The eosinophylic pneumonias are The eosinophylic pneumonias are characterized by eosinophilic characterized by eosinophilic pulmonary infiltrates and commonly pulmonary infiltrates and commonly peripherial blood eosinophylia.peripherial blood eosinophylia.

Known and unknown etiologyKnown and unknown etiology

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Eosinophylic pneumoniasEosinophylic pneumonias Known etiologyKnown etiology

Allergic bronchopulmonary aspergillosis (ABPA)Allergic bronchopulmonary aspergillosis (ABPA) Parasitic infestations (ascaris, toxocara,etc)Parasitic infestations (ascaris, toxocara,etc) Drug reactions (nitrofurantoin, sulphonamides)Drug reactions (nitrofurantoin, sulphonamides)

Idiopathic (unknown etiology)Idiopathic (unknown etiology) Löffler’s syLöffler’s sy

Benign, acute eosinophilic pneumonia (AEP) with Benign, acute eosinophilic pneumonia (AEP) with migrating pulmonary infiltrates and minimal clinical migrating pulmonary infiltrates and minimal clinical manifestation.manifestation.

Chr. eosinophilic pneumonia (CEP)Chr. eosinophilic pneumonia (CEP) Symptoms: cough, sweats, fever, anorexia, weight loss, Symptoms: cough, sweats, fever, anorexia, weight loss,

chillschills X-ray: Peripherial infiltratesX-ray: Peripherial infiltrates

Allergic granulomatosis of Churg and StraussAllergic granulomatosis of Churg and Strauss Hypereosinophilic sy (HES)Hypereosinophilic sy (HES)

Therapy: corticosteroidsTherapy: corticosteroids

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PNEUMOCONIOSIS

Etiologic agents: inhalation of inorganic dusts

metal dusts free silica coal dusts

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HYPERSENSITIVE PNEUMONITIS(Extrinic allergic alveolitis)

It is an immunologically induced inflammation of lung parenchyma involving alveolar walls and terminal airways secondary to repeated inhalation of a variety of organic dusts and other agents by susceptible host.

Manifestations:Farmer’s lung (1932) – thermophylic actinomycetesBird fancier’s breeder’s or handler’s lung

Miller’s lungBagassosisByssinosis

Air conditioner’s lungCoffee worker’s lung

50Thank you for your attention!