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Interstitial Lung Disease:Clinical Approach to Diagnosis

Rupal J. Shah, MD MSDirector, Interstitial Lung Disease ClinicUniversity of California, San Francisco

Disclosures

• Nothing to Disclose

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Outline

• What is ILD?

• Diagnostic Approach

• Specific types of ILD

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What is the pulmonary interstitium?

• Anatomic space that is lined by epithelial and endothelial cells

• Contains collagen, elastin, reticulin, ECM

• Also in the connective tissue of the lung (interlobular septa, visceral pleura, peribronchovascularsheaths)

Not Just Interstitial

• Misnomer because many ILD’s affect the airways, parenchyma, blood vessels and pleura

• More accurately described as diffuse parenchymal lung disease

• Over 100 types of ILD’s

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Farrand, E et al The hospitalized patient with interstitial lung disease: A hospitalist primer J Hosp Med 2017

Epidemiology

• Very difficult to estimate

• Prevalence:

– IPF: 10‐40/100,000 adult per year

– All ILD: 60‐80/100,000 adults per year

• COPD: 5% of the population (16 million)

Raghu, et al Incidence and prevalence of IPF AJRCCM 2006Coultas DB The epidemiology of interstitial lung disease AJRCCM 1994

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Epidemiology

Lederer DJ, et al Idiopathic pulmonary fibrosis NEJM 2018

Diagnosis

• Challenge: Presentation is usually nonspecific

• Average time from symptom onset to diagnosis: 1‐2 years

• Early recognition is important!

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Outline

• What is ILD?

• Diagnostic Approach

• Specific types of ILD

Clinical Evaluation: History

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Elements Examples Demographics

Age: IPF>50 years, 20-40: CTD, sarcoid, LAM, LCH, familial Female: LAM, CTD-ILD, Men: RA-ILD, occupational

Onset of Symptoms Timing can guide the differential (acute: COP, CTD-ILD, chronic: IPF, sarcoid)

Smoking History LCH, DIP, RB-ILD, IPF

Family History Premature graying, history of ILD

Review of Systems Arthralgias, Raynaud’s, Myositis, Dysphagia/Reflux

Drugs Occupational/Environmental Exposures

Pneumotox.com Don’t forget OTC and illicit Birds/Mold Asbestos, Silica Next Slide

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Clinical Evaluation: Physical Exam

14Travis, WD et al An official ATS/ERS statement: Update of the international multidisciplinary classification of IIP AJRCCM 2013

Elements Examples Lung

Nonspecific, typically crackles or rales

Cardiac Signs of pulmonary HTN Edema, augmented P2, RV heave

Extremities Clubbing, joint deformities, weakness

Skin Alopecia, angiofibromas, Gottron’s papules, mechanic’s hands, sclerodactyly (next slide)

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Clinical Evaluation: Physical Exam

15Folliculofibroma: BHD Angiofibroma: LAM

Diagnostic Tests

• Imaging (to be discussed by Dr. Elicker)

• Pulmonary Function Tests

• Laboratory

• Bronchoscopy

• Surgical lung biopsy

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PFT Interpretation

Order full PFT’s

Pulmonary Function Test

Spirometry Predicted Observed %PredFVC 3.72 2.24 60%FEV1 3.06 1.78 58%FEV1/FVC 82 79 96%

PlethysmographyTLC 5.26 3.38 64%

DiffusionDiffusing Capacity  29.01 8.01 28%

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Clinical Evaluation: Laboratory Analysis

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Elements Comment

CBC with differential Macrocytosis (telomeropathy)Eosinophilia (CEP)

Autoimmune serologies Next slide

HP precipitans Poor sensitivity and specificity, limited range of antigens tested

Genetic testing Selected cases (e.g. BHD), emerging for FPF

Telomere length measurement Emerging

VEGF‐D Lymphangioleiomyomatosis

Travis, WD et al An official ATS/ERS statement: Update of the international multidisciplinary classification of IIP AJRCCM 2013

Autoimmune Serologies

• Initial Evaluation

– ANA

– RF/CCP

– ANCA

– Myositis Panel

– SSa/SSb

Alsumrain, M Utility of autoimmune serology testing in the assessment of uncharacterized ILD: a large retrospective cohort review Respir Res 2017

*yield is lower with increasing age

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Bronchoscopy

Meyer KC, Raghu G. Bronchoalveolar lavage for the evaluation of interstitial lung disease: is it clinically useful? Eur Respir J. 2011;38:761-769.

Surgical Lung Biopsy• Mortality

– 1.7% (elective)– 16% (non‐elective)

22Hutchinson,JP et al In-Hospital Mortality after SLB for ILD in the US 2000-2011 AJRCCM 2015

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History, Physical Exam,CT scan, labs

Diagnosis!IPFHP (some)LCH, AP, LAMCTD‐ILDSome occupational lung diseases

Is bronchoscopy safe and indicated?SarcoidMalignancyEosinophilic pneumoniaCOP

NoSurgical Lung Biopsy

Bronchoscopy Diagnostic

Confident diagnosis

Diagnosis of highest probability (MDC)

Procedures are unsafe

Non diagnostic

Non diagnostic

Adapted from Wells, AU ILD guideline: the BTS with Thoracic society of Australia and New Zealand and Irish Thoracic Society Thorax 2008

Multi Disciplinary Conference

Flaherty KR, King TE, Raghu G, et al. Idiopathic interstitial pneumonia: what is the effect of a multidisciplinary approach to diagnosis? Am J Respir Crit Care Med. 2004;170:904-910.

• Agreement is best when there is a consensus discussion between clinicians, radiology, and pathology 

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Outline

• What is ILD?

• Diagnostic Approach

• Specific types of ILD

• Available therapies

• Cases

Idiopathic Pulmonary Fibrosis• IPF is a specific form of chronic, 

progressive fibrotic interstitial lung disease that occurs in older adults and is characterized by radiographic or pathologic usual interstitial pneumoniawithout a secondary cause

• UIP pattern: peripheral basilar reticulation, traction bronchiectasis and honeycombing without other features (i.e. ground glass, air trapping, etc)– CTD, asbestosis, chronic HP, XRT

11/7/2018 26Official ATS/ERS/JRS/ALAT Guidelines on Idiopathic Pulmonary Fibrosis. AJRCCM 2011;183:788

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IPF: Why is diagnosis important?

• Median survival ~4 years

• Acute exacerbation rate 5‐10% per year

27Ryerson CJ et al Predicting survival across interstitial lung disease: the ILD-GAP model Chest 2014

Hypersensitivity Pneumonitis• No consensus diagnostic criteria

– Classic imaging + good exposure

– Lung biopsy

• Described as acute, sub-acute, and chronic

• Over 200 exposures identified:– Typically related to mold or bird products

• Treatment– Remove exposure

– Prednisone +/- mycophenolate or azathioprine

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Connective Tissue Disease

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CTD  Diagnosis 

Systemic Sclerosis  

Esophageal Dilation 

Rheumatoid Arthritis  Consider drug induced lung injury for new/worsening ILD  

Dermatomyositis/Polymyositis  Myositis may be subtle ILD can come first ANA can be negative  

Sjogren’s Syndrome  Cysts on HRCT  

Lupus  ILD is unsual 

Adapted from Vij, R Diagnosis and Treatment of CTD-ILD Chest 2013

Interstitial Lung Abnormalities• Increased lung density on CT scans in patients with no history of ILD

• 2‐10% of the population• Association with reduction in PFT, exercise capacity, development of ILD, and mortality

• Refer to pulmonary

Putman, RK et al Association between ILA and All‐cause mortality JAMA 2016

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Conclusions

• Multiple types of ILD

• Consider in older patient with cough or subacute shortness of breath

• Evaluation starts with high resolution CT, may need surgical lung biopsy

• Important to distinguish IPF from other types of ILD as treatment differs

Refer to us!

• UCSF ILD Program

• https://www.ucsfhealth.org/clinic/interstitial_lung_disease_program/#

• 415.353.2577

• Rupal.shah@ucsf.edu

Environmental Exposure Assessment Form

Interstitial lung disease (ILD) can be a progressive scarring disease of the lung. Some types of ILD can be related to environmental exposures. UCSF’s Interstitial Lung Disease Program developed this assessment form to help gauge your potential exposures. This checklist does not include every possible exposure and having an exposure does not mean that it is the cause of your lung disease. This form is best used in consultation with an expert in interstitial lung disease.

General

Approximate year your house/residence was built: _________________

Address: ______________________________________________________________

Is the location: 1. Urban 2. Suburban 3. Rural

Race: 1. Caucasian 2. Hispanic 3. African American 4. Asian 5. Other (specify)

Are you an immigrant?

If yes, from which country/region? 1. Mexico 2. Asia 3. Canada 4. Other (specify) Yes No

Does your residence or office smell musty? Yes No

Has there been a history of flooding? Yes No

Is there water damage to the walls or ceilings

(Look behind furniture that is up against the walls in your rooms)? Yes No

Do you have carpeting?

If yes, When was it installed? __________           

Is the carpeting steam-cleaned regularly?           

Was the carpeting installed over cement?

Yes No

Yes No

Yes No

Do you have a hot tub or sauna? How often do you use it? ___________ Yes No

Are there any birds (pets or nesting) on the property?

If yes, which species? 1. Finch 2. Cockatiel 3. Parakeet 4. Other (specify)

How long was the exposure? _______ days/weeks/months/years

Was the bird(s) kept indoors?

Yes No

Yes No

Do you have any decorations, clothing or furniture with bird feathers (e.g. down feathers)? Yes No

Do you have a lot of plants in your home or office? Yes No

Do you have a fish tank(s)? Yes No

Do the window sills in your home of office show any signs of mold? Yes No

Do you use a swamp cooler? Yes No

Do you use humidifiers, dehumidifiers or vaporizers? Yes No

Do you use ozone cleaners, HEPA filters or other air filters? Yes No

Are there any water features, such as a fountain, in your home? Yes No

Do you have a water collection system, cistern or water storage unit? Yes No

Heating your residence

Do you have central or forced-air heating

If yes, is there mold on filters? Yes No

Do you use a wood-burning stove at least once a week? Yes No

Kitchen

Do you have any appliances or sinks that leak water or have a water pan to change? Yes No

Does your dishwasher leak/overflow or smell musty? Yes No

To refer a patient: Interstitial Lung Disease Program • Phone 415-353-2577 • Fax 415-353-8944 Lung Transplant Program • Phone 415-353-4145 • Fax 415-353-4166Referral forms can be found at www.ucsfhealth.org/referral

To refer a patient: Interstitial Lung Disease Program • Phone 415-353-2577 • Fax 415-353-8944 Lung Transplant Program • Phone 415-353-4145 • Fax 415-353-4166Referral forms can be found at www.ucsfhealth.org/referral

Bathroom

Are there signs of mold or mildew on walls, ceilings, tiles or curtains? Yes No

Is there a working exhaust fan? Yes No

Bedrooms

Do you have any clothes, jackets, pillows or comforters that contain down (fine bird feathers)? Yes No

Do you use a Sleep Number® (or similar) bed or water bed? Yes No

Closets

Are any leather clothes or shoes stored in your closets covered with a white or black film? Yes No

Are the walls of the closets discolored or are they covered with a black or white film? Yes No

Other rooms in your home

Does your clothes washing machine smell musty (if you have one in your residence)? Yes No

Is there a hobby room or workshop in or attached to your home, including a garage used in this way? Yes No

Are there any rooms located below ground or built on the side of a hill? Yes No

Basement

Is there any mold or mildew on walls or boxes? Yes No

Are there times during the year when water gets into the basement? Yes No

Do you spend time in the basement? Yes No

Is there carpeting in the basement?

If yes, was it installed over cement? Yes No

Yes No

Outside your home

Is there a compost pile in or near your home? Yes No

Is there any evidence of birds roosting on the roof, rafters, sills or decks? Yes No

Outdoor activities

Do you work with potting soils, moist soil or compost on a regular basis? Yes No

Do you hunt in duck blinds or have exposure to a lot of feathers? Yes No

Have you been exposed to moldy hay or grain? Yes No

Have you been involved in the packaging industry? Yes No

Have you been a farm worker?

If yes, for how many years? Yes No

Please list the products cultivated (e.g. almonds, grapes, etc.).

Have you been exposed to pesticides and/or other chemicals? Yes No

Did you ever smoke?

If yes: Packs/day: _________ Number of years: _________

Do you currently smoke?

If no, when did you quit? ____________________

Have you ever lived with a smoker?

If yes, for how long? ____________________________

Yes No

Yes No

Yes No

Name_________________________________ Date Completed_______________ revised 07.18