Case Approach in Interstitial

Lung DiseasesSuree Sompradeekul, MD, FCCPAssistant Professor of Medicine

Division of Respiratory Disease & TuberculosisDept of Medicine, Siriraj Hospital

Diffuse Diffuse parenchymalparenchymal lung diseaselung disease

DPLD of known DPLD of known cause or associationcause or association

Idiopathic Idiopathic interstitial interstitial

pneumoniaspneumonias

GranulomatousGranulomatous Other forms of Other forms of interstitial pneumonia interstitial pneumonia

e.g. LAM, PLCH, e.g. LAM, PLCH, eosinophiliceosinophilic

pneumonia, etc.pneumonia, etc.Idiopathic Idiopathic pulmonary pulmonary

fibrosis fibrosis

Interstitial pneumonia Interstitial pneumonia other than idiopathicother than idiopathicpulmonary fibrosispulmonary fibrosis

DesquamativeDesquamative interstitialinterstitialpneumonia pneumonia

Respiratory Respiratory bronchiolitisbronchiolitisInterstitial lung diseaseInterstitial lung disease

Acute interstitial Acute interstitial pneumonia pneumonia

Cryptogenic Cryptogenic organisingorganising pneumoniapneumonia

NonNon--specificspecificInterstitial pneumoniaInterstitial pneumonia

LymphocyticLymphocyticInterstitial pneumoniaInterstitial pneumonia

ILD associated with systemic diseaseRheumatogical

Systemic sclerosisRheumatoid arthritisSystemic lupus erythematosusSjÖgren’s syndromeAnkylosing spondylitisPolymyositis/dermatomyositisMixed connective tissue disease

VasculitisGiant cell arteritisTakayasu’s arteritisMicroscopic polyangiitisWegener’s granulomatosisChurg-Strauss granulomatosisBehcet’s syndromePulmonary-renal syndrome (including Goodpasture’s syndrome)Capillaritis

ILD associated with systemic disease

Vascular Antiphospholipid syndromeCoagulopathiesArteriovenous malformationsPrimary pulmonary hypertensionIdiopathic pulmonary hemosiderosisPulmonary veno-occlusive disease

Disease caused by environmental triggers or drug ingestion

Drug*ChemotherapeuticCardiovascularAntibioticsAnti-inflammatoryIllicitPsychotropicRadiationPesticidesOxygen

Environmental (organic causes)Extrinsic allergic alveolitis

FungalBacterialAvianChemical

Inorganic causesFibrogenic inorganic dusts

AsbestosSilicaHard metal alloyBerylliumCoalAluminium

Non-fibrogenicSiderosisStannosisBaritosisAntimony

Idiopathic interstitial pneumoniasIdiopathic pulmonary fibrosis (or cryptogenic fibrosing alveolitis)Desquamative interstitial pneumonia (DIP)Acute interstitial pneumonia (AIP)Non-specific interstitial pneumonia (NSIP)Respiratory bronchiolitis/interstitial lung disease (RB-ILD)Cryptogenic organising pneumonia (COP or idiopathic BOOP)Lymphocytic interstitial pneumonia (LIP)

Histologic & Clinical Classification of ILDHistologic patterns Clinical-Radiologic-

Pathologic DxUsual interstitial pneumonitis

Nonspecific interstitial pneumoniaOrganizing pneumonia

Diffuse alveolar damageRespiratory bronchiolitis

Desquamative interstitial pneumoniaLymphoid interstitial pneumonia

Idiopathic pulmonary fibrosis/cryptogenic fibrosing alveolitisNonspecific interstitial pneumonia (provisional)Cryptogenic organizing pneumonia (BOOP)Acute interstitial pneumoniaRespiratory bronchiolitis interstitial lung diseaseDesquamative interstitial pneumonia

Lymphoid interstitial pneumonia

Granulomatous diseasesSarcoidosisBerylliosisHypersensitivity pneumonitis or Extrinsic allergic alveolitisLangerhan’s cell histiocytosisWegener’s granulomatosisChurg-Strauss syndromeLymphomatoid granulomatosisBronchocentric granulomatosis

Other diffuse lung diseasesInherited disorders

Tuberous sclerosisNeurofibromatosisHermansky-Pudlak syndromeLipid storage disordersFamilial fibrosing alveolitis

Pulmonary eosinophiliaKnown causes, e.g. fungi, parasites, drugsUnknown causes, e.g. acute and chronic idiopathic

eosinophilic pneumoniaLymphangioleiomyomatosisAlveolar proteinosisAlveolar microlithiasisAmyloidosisChronic aspirationChronic left heart failure

Clinical manifestationProgressive dyspneaNon-productive coughPleuritic chest pain (pneumothorax)Hemoptysis +/- Fe def anemiaWheezingAbnormal CXRSymptoms related to associated diseases e.g. CNTRestrictive pattern from spirometry

Physical examinationIncreased RRRespiratory distressCracklesInspiratory squeaks – late inspiratoryhigh-pitched rhonchi; bronchiolitisCyanosis, clubbing of fingers, corpulmonale – advanced diseaseExtrapulmonary findings

Extrapulmonary findingsHypertensionSkin: EN, maculopapular rash, heliotrope, telangiectasis, Raynaud’s, Café-au-lait spots, vasculitis, subcut nodules, albinism, calcinosisEye: uveitis, scleritis, keratoconjunctivitissiccaSalivary gland enlargementLymphadenopathyHepatospenomegalyPericarditis, myocarditisMuscle weakness

Duration of illnessAcute (days to weeks)

Acute idiopathic interstitial pneumonia (AIP, Hammon-Rich syndrome)Eosinophilic pneumoniaHypersensitivity pneumoniaBronchiolitis obliterans with organizing pneumonia (BOOP) or cryptogenic organizing pneumonia (COP)

Subacute (weeks to months)SarcoidosisDrug-inducedAlveolar hemorrhage syndromesIdiopathic BOOPCNT (SLE, polymyositis)

Chronic (months to years)Idiopathic pulmonary fibrosis (IPF)SarcoidosisPulmonary Langerhans cell histiocytosis (PLCH) or eosinophilicgranuloma (EG)

Occupation & environmental exposures

Inhaled organic dusts (hypersensitivity pneumonitis)

Thermophilic fungi; farmer’s lung, grain handler’s lung, humidifier or air conditioner lungBacteria (Bacillus spp); humidifier lungTrue fungi (aspergillus, cryptostorma coricale, penicilliumAnimal proteins; bird fancier’s disease

Occupation & environmental exposuresInhaled inorganic dust

SilicatesSilica (silicosis)Asbestosis (asbestosis)Talc (talcosis)Kaolin or china clayDiatomaceous earth (Fuller’s earth)Nepheline (hard rock)Aluminum silicates (sericite, sillimanite, ziolite)Portland cementMicaBeryllium (berylliosis)

CarbonCoal dust (pneumoconiosis)graphite

MetalsTins (stannosis)Aluminum; powdered aluminum, bauxiteHard metal dusts: cadmium, titanium, tungsten, hafnium, niobium, cobalt, vanadium carbidesIron (siderosis, arc welder’s lung)AntimonyHematite (siderosilicosis)Mixed dusts of silver and iron oxide (argyrodiserosis)Barium (powder of baryteor BaSO4- (baritosis)CuSO4 neutralized with hydrated lime (vineyard sprayer’s lung)Rare earths, Ocerium scandium, yttrium , lanthanum

Occupation & environmental exposuresInhaled other agents

Chemical sourcesSynthetic-fiber lung (nylon, acrylic, polyesters, orlon)Bakelite worker’s lungVinyl chloride, polyvinyl chloride powder

GasesOxygenOxides of nitrogensulfur dioxideChlorine gasesMethyl isocyanate

FumesOxides of zinc, copper, manganese, cadmium, iron, magnesium, nickel, brass, selenium, tin, antimonyDiphenylmethane diisocyanateTrimellitic anhydride toxicity

VaporsHydrocarbonsThermosetting resins (rubber tire workers)Toluene diisocyanate (TDI-asthmatic reactions prominent)Mercury

AerosolsOilsFatsPyrethrum (natural insecticide)

Laboratory dataLeukopenia: sarcoidosis, CNT, lymphoma, drug-inducedLeukocytosis: HP, lymphoma, vasculitisEosinophilia: eosinophilic pneumonia, sarcoidosis, vasculitis, drug-induced (sulfa, methotrexate)Thrombocytopenia: sarcoidosis, CNT, drug-induced, Gaucher’s disHemolytic anemia: CNT sarcoidosis, lymphoma, drug-inducedNormocytic anemia: alv hemorrhage syndrome, CNT, lymphangitic carcinomatosisElevated LDH: alv proteinosis, IPFHypogammaglobulinemia: LIPHypergammaglobulinemia: CNT,sarcoidosis, vasculitis, LIP, lymphoma, silicosis

Laboratory dataSerum immune complexes: IPF, LIP, vasculitis, CNT, EGACE: sarcoidosis, HP, silicosis, Gaucher’s diseaseAntibasement membrane Ab (anti-GBM):Goodpasture’s syndromeANCA: Wegener’s granulomatosis, Churg-Strauss syndrome, microscopic polyangiitisSerum precipitating Ab: HPLymphocyte transformation test to specific antigens: chronic beryllium disease, aluminum potroom workers disease, gold-induced pneumonitis

IPFIPF DIPDIP RBRB--ILDILD AIPAIP BOOPBOOP NSIPNSIP

Age (years) 65 40 35 50 55 55

Occurrence in children

No Rare No Rare No Occasional

Onset Chronic Chronic Chronic Acute Acute/subacute

Subacute/Chronic

Clubbing Frequent Frequent No No No Occasional

Fever Rare No No 50% 70% 20%

Mortality (%) 70 27 0 8 13 11

Mean survival 2.8 years 12 years Not reduced

1.5 months

> 10 years

13 years

Response to corticosteroids

Poor Good Good Poor Good Good

Disease Radiographic features CT Differential Dx

IPF Peripheral, basal reticular abnormalities with volume loss

Asbestosis, CNT, HP, sarcoidosis

DIP Ground glass opacity RB-ILD, HP, sarcoidosis, PCP

RB-ILD Bronchial wall thickening, ground glass opacity

DIP, NSIP, HP

AIP Progressive diffuse ground glass density/consolidation

Hydrostatic edema, pneumonia, acute eosinophilic pneumonia

COP Patchy bilateral consolidation Infection, vasculitis, sarcoidosis, alveolar carcinoma, lymphoma, eosinophilic pneumonia, NSIP

LIP Reticular opacity, nodules Sarcoidosis, lymphangiticcarcinomatosis, PLCH

NSIP Ground glass and reticular opacity

UIP, DIP, COP, HP

Disease Distribution CT Pattern

IPF Peripheral, subpleural, basal Reticular, honeycombing, traction bronchiectasis, minor focal ground-glass

DIP Peripheral, subpleural, basal Predominant ground glass, minor reticular lines

RB-ILD Diffuse Bronchiolar-wall thickening, centrilobular nodules, patchy ground-glass

AIP Diffuse Ground glass with focal lobular sparing, consolidation, later traction bronchiectasis

COP Subpleural, peribronchial Patchy consolidation and/or nodules

LIP Diffuse Centrilobular nodules, ground glass attenuation, septal and bronchial wall thickening, thin-walled cysts

NSIP Peripheral, subpleural Predominant ground glass, basal reticular lines, consolidation

Acute interstitial pneumoniaDiffuse alveolar hemorrhage (vasculitis or coagulopathy most common causes)Acute pneumonia due to rheumatological diseaseDrugs (selected)Eosinophilic lung disease, acute or chronicCryptogenic and known causes of organizing pneumonia (BOOP)Mimics

− Pulmonary edema of any cause− Infection, especially opportunistic with

Pneumocystis carinii− Acute respiratory distress syndrome

Acute onset ILD

Diffuse lung disease with characteristic features on HRCT

Idiopathic pulmonary fibrosis (cryptogenic fibrosing alveolitis)Desquamative interstitial pneumoniaExtrinsic allergic alveolitisSarcoidosisLangerhans cell histiocytosisLymphangioleiomyomatosisAlveolar proteinosisLymphangitic carcinomatosis

Predominant distribution on HRCTUpper-lobe predominance Sarcoidosis

Coalworker’s pneumoconiosisSilicosisEosinophilic pneumoniaLangerhans cell histiocytosisExtrinsic allergic alveolitis

Lower-lobe predominance Idiopathic pulmonary fibrosisDesquamative interstitial pneumonia AsbestosisCollagen vascular disease

Peripheral predominance Idiopathic pulmonary fibrosisDesquamative interstitial pneumoniaAsbestosisCollagen vascular diseaseEosinophilic pneumoniaOrganising pneumonia

Central (peribronchovascular) predominance

SarcoidosisLymphangitis carcinomatosis

Pattern in HRCTLinear and reticular Idiopathic pulmonary fibrosis

Collagen vascular diseaseAsbestosis

Nodular or reticulonodular SarcoidosisSilicosisLymphangitis carcinomatosis

Parenchymal opacification(consolidation/ground-glass)

Organising pneumoniaExtrinsic allergic alveolitisDesquamative interstitial pneumoniaRespiratory bronchiolitis/interstitial lung

diseaseChronic eosinophilic pneumonia HaemorrhageAlveolar proteinosis

Cystic abnormalities Langerhans cell histiocytosisLymphangioleiomyomatosis

Neutrophilic(± eosinophilic)

Idiopathic pulmonary fibrosis Desquamative interstitial pneumonia Collagen vascular diseaseAsbestosisAcute interstitial pneumonia

Lymphocytic SarcoidosisExtrinsic allergic alveolitisSilicosisLymphocytic interstitial pneumonia

Eosinophilic (Chronic) eosinophilic pneumonia Churg-Strauss syndromeHypereosinophilic syndrome

Mixed cellularity Bronchiolitis obliterans organizing pneumoniaCollagen/vascular diseaseNon-specific interstitial pneumonia

Abnormal macrophage morphology

Extrinsic allergic alveolitisAlveolar proteinosisRespiratory bronchiolitis/interstitial lung diseaseAlveolar hemorrhage

BAL cell

Initial assessment:• Breathlessness• Crackles on auscultation• Pulmonary function: reduced

TL CO, restrictive defect• Chest radiograph: compatible

with interstitial fibrosis• Absence of environmental or systemic disease cause

• High-resolution CT• Bronchoalveolar lavage± transbronchial biopsy

Diagnosis and prognosis

Yes No

Thoracoscopic or open lung biopsy

• Reversible disease on biopsy or CT ?• Progressive disease ?• Moderate functional impairment ?

Yes No

Treat If deteriorates

Observe (but monitor with serial pulmonary function tests)

Thank you & GOOD LUCK !!!!!