Interstitial Lung Disease for the PCP Jeff Swigris, DO, MS Associate Professor of Medicine Interstitial Lung Disease Program National Jewish Health Denver, Colorado

Objectives  Define the interstitium  Define ILD  Finding the cause  Clinical presentation  Therapy  Define internist’s role

Where is the interstitium?

170, ,000 alveoli in here ~1-1.5cm

Classification based on etiology ILD Exposure-related mold, bacteria, birds medications XRT dusts cigarette smoke Idiopathic Sarcoidosis IIP Genetic FPF CTD-related RA Systemic sclerosis PM/DM Sjögren’s syndrome MCTD UCTD SLE

DAD DIP OP RB-ILD CFA IPF BOOP COP LIP NSIP UIP AIP Hamman-Rich BO HP UIPOB

Idiopathic interstitial pneumonias (IIP)  Idiopathic pulmonary fibrosis (IPF)  Nonspecific interstitial pneumonia (NSIP)  Cryptogenic organizing pneumonia (COP)  (Idiopathic BOOP)  Acute interstitial pneumonia (AIP)  Desquamative interstitial pneumonia (DIP)  Respiratory bronchiolitis-ILD (RB-ILD)  Lymphoid interstitial pneumonia (LIP)

Classification based on histology

ILD Exposure-related mold, bacteria, birds medications XRT dusts cigarette smoke Idiopathic Sarcoidosis LAM IIP Genetic FPF Autoimmune-related RA Systemic sclerosis PM/DM Sjögren’s syndrome MCTD

Nicholson et al. Am J Respir Crit Care Med 2000;162: Scar = bad prognosis Fibrosis Inflammation

What type of fibrosis is the PCP most likely to see?  ++++ Idiopathic pulmonary fibrosis (IPF)  Aging population  ++++ Connective tissue disease-related  RA  + Chronic hypersensitivity pneumonitis  Organic exposure (M/M/B/B

Making the diagnosis You have to be a detective  History  Exam  Pulmonary physiology  Radiography  +/- surgical lung biopsy

History: chief complaint  Typically, ILD presents with:  Dyspnea—subacute, insidious onset  “I thought I was just…”  Getting older  5# heavier  Out of shape  +/- dry cough  Fatigue  No wheeze, no chest pain

History History Be a good detective  Symptoms/existence of concurrent disease  Patients may…  1. Have known CTD  2. Dyspnea from occult CTD-related ILD  Family history  Pulmonary fibrosis  Rheumatologic illness

History: exposures History: exposures Be a good detective  Smoking PEARL  IPF  DIP, RB-ILD, PLCH  Goodpasture’s

History: exposures History: exposures Be a good detective  Current or previous medications   Chemotherapy  Amiodarone  Nitrofurantoin  External beam radiation  Current or previous recreational drug use  Occupational, environmental, avocational PEARL

History: exposures History: exposures Be a good detective  Microbial agents  M/M/B/B  Hot tubs (indoor/enclosed)  Basement shower  Free-standing humidifiers  Water damage to home  Cooling systems (swamp cooler)

History: exposures History: exposures Be a good detective  Birds (proteins)  Bloom on feathers  Mucin in excrement  Feather pillow/down comforter  Fumes, dusts, gases  Asbestos  Beryllium

History: connective tissue diseases  RA  Symmetric arthritis/small joints  Morning stiffness  Subcutaneous nodules  Smoker PEARL

History: connective tissue diseases  SSc  Raynauds  After 40 y.o. in FEMALE  After 30 y.o. in MALE  Esophageal dysmotility  Skin tightening PEARL

History: connective tissue diseases   Sjögren’s Syndrome  Dry eyes/mouth  Dental caries

History: connective tissue diseases  PM/DM  Proximal muscle weakness  Rashes  Rough skin on the hands

Physical Exam

Physical examination Physical examination You’re still a detective  Skin  Rash  Purupura  Telangiectasia  Nodules  Calcinosis

Physical examination  Nails  Clubbing  COPD no clubbing PEARL

Nailfold capillaroscopy Normal Abnormal Fischer et al. Chest. In press

Physical examination  Chest  Velcro crackles are NEVER normal Must listen here PEARL

Laboratory  ANA—the pattern matters  Nucleolar ANA any titer – TO RHEUM  SSA is a myositis associated ab (ANA -)  ACE level non-specific  Don’t order it  HP panels unhelpful  Precipitating IgG to organic antigens  Don’t order them PEARLS

Laboratory  Isolated high MCV  Methotrexate  Azathioprine  ??? Telomerase abnormality  Elevated MCV  History of bone marrow irregularities  Premature graying  Cryptogenic cirrhosis  Pulmonary fibrosis PEARLS

Pulmonary physiology  Pulmonary function testing  Gas exchange

Pulmonary function testing  Lung volumes  Spirometry  DLCO  ABG

Patients with ILD have Restrictive Physiology  Low static lung volumes  Low forced volumes  Low FVC  Low FEV1  Normal FEV1/FVC

Volumes may be normal if… + …but the DLCO will be very low

Impaired Gas Exchange  SpO2 at rest is unhelpful  Exercise oximetry  Never normal to desaturate  6-minute walk test PEARL

Radiology: diagnosing ILD  “ILD protocol” HRCT  No IV contrast  Supine and prone  Inspiratory and expiratory images  Reconstruction algorithm — 1-1.5mm thick

HRCT Terminology  Opacities  Lines (reticular)  Dots or Circles (nodules)  Patches  Attenuation (shade of gray)  Consolidation – obscures underlying vessels  Ground glass – does not obscure underlying vessels

Lower zone Peripheral/subpleural Reticular opacities Traction bronchiectasis Interlobular septal thickening

Honeycombing

Ground glass opacities

Lung biopsy  Transbronchial biopsy  Sarcoidosis  Lymphangitic carcinomatosis  Subacute HP  Surgical  Thorascopic  Usually not if CTD-related

Putting it all Together  History  Exam  Labs  ANA, RF, anti-CCP  Physiology  Full PFTs  Gas exchange  6MWT  Radiology  HRCT  Pathology Integrate to get “summary diagnosis”

Therapy for ILD  Not all patients require therapy  General: treat clinically significant, progressive dz  All therapeutic regimens require monitoring  Glucocorticoids may be the mainstay  Steroid-sparing / immune-suppressing / immunomodulatory / cytotoxic agents  Nuance

STABILITY = SUCCESS I don’t want my patients ILD leaving clinic thinking they don’t have a serious condition I don’t want my patients with ILD leaving clinic thinking they should go home, sit on their couch and die

Gauging Response  Q 3mos visits to pulm  Subjective  Symptoms  FVC  DLCO  6MWT  Not HRCT unless scenario mandates

Internist: before ILD dx  Thorough history and examination  Order HRCT  Order serologies  ANA with pattern and ENA panel  RF/anti-CCP  Order PFTs/6MWT/HRCT  Refer: ILD on HRCT

Internist: after ILD dx  Monitor for side effects of therapy  Glucocorticoids  Weight  Sugar  BP  Eyes  Bones  Be on the lookout for infection  Monitor need for oxygen  Communicate with patient  Mood: therapy needed?  End-of-life discussions

Internist: after ILD dx  Refer to pulmonary rehabilitation  Vaccines  Sunscreen for all on immunosuppressive Tx  Monthly labs for all on immunosuppressive Tx

Five Main Points  You will see ILD — be a detective  Velcro crackles never normal — get HRCT  Surgical lung biopsy often needed to make a confident diagnosis  All patients and most therapies require monitoring—the internist is vital here