Update in Interstitial Lung Diseases - csim.ca · Idiopathic Lymphoid Interstitial Pneumonia -...

Update in Interstitial Lung Diseases

Charlene D FellCSIM 2018

cfell@ucalgary.ca

Disclosures

• Faculty: Charlene D Fell

• Relationships with commercial interests:– Grants/Research Support: Roche Canada– Educational Grants: Boehringer Ingelheim, CPFF– Scientific Advisory Boards: Boehringer Ingelheim, Roche Canada– Speakers Bureau/Honoraria: Boehringer Ingelheim, Roche Canada– Consulting Fees: Boehringer Ingelheim, Roche Canada

– Employment: – University of Calgary and Alberta Health Services

At the end of this workshop you’ll be able to:

• Develop an approach to diagnose and classify ILD.• Screen patients for environmental and

occupational causes of ILD.• (Screen patients for rheumatological causes of

ILD).• Discuss recent updates in anti-fibrotic therapy.

Objectives

Hopkins, RB et al. Eur Respir J. 2016. 48:187-95.

Epidemiology of IPF in Canada

Incidence* Prevalence*

Broad Narrow Broad Narrow

Men 21.3 10.5 45.4 22.3

Women 16.2 7.4 38.2 17.7

Total 18.7 9.0 41.8 20.0

Hopkins, RB et al. Eur Respir J. 2016. 48:187-95.Raghu, G et al. AJRCCM 2006.

Navaratnam, V et al. Thorax 2011.

* Per 100,000 persons

Incidence* Prevalence*

Broad Narrow Broad Narrow

USA 16.3 6.8 42.7 14.0

UK 7.44 - - -

* Per 100,000 persons

Prevalence rates of idiopathic pulmonary fibrosis by the narrow definition, per 100 000 persons aged ≥50 years, by province and sex, in 2011.

Robert B. Hopkins et al. Eur Respir J 2016;48:187-195©2016 by European Respiratory Society

Survival estimates for 2008 incident cases, Ontario

Hopkins, RB et al. Eur Respir J. 2016. 48:187-95.

Baseline Characteristics And Comorbidities in the CAnadian REgistry for Pulmonary Fibrosis (CARE-PF)

JH. Fisher1, S. Shapera1, M. Algamdi2,3,4, J. Morisset5, KA. Johannson6Mo, CD. Fell6, M. Kolb7, H. Manganas5, G. Cox7, N. Khalil2, AJ. Halayko8,9, AS. Gershon1,10, T. To10,11,12, N. Hambly7, M.

Sadatsafavi13,14, P. Wilcox2,3, C. J. Ryerson2,3

Most common diagnoses among 1285 ILD patients enrolled in the CARE-PF study

At the end of this workshop you’ll be able to:

Develop an approach to diagnose and classify ILD.

Screen patients for environmental and occupational causes of ILD.

(Screen patients for rheumatological causes of ILD).

• Discuss recent updates in anti-fibrotic therapy.

Objectives

56 male ex-smoker Control systems

engineer

PMHx: GERD (PPI)

3 year history: Exertional dyspnea

(stairs) Exertional cough

Idiopathic Interstitial

Pneumonias

Major IIPs- IPF Idiopathic Pulmonary Fibrosis- iNSIP Idiopathic Nonspecific Interstitial Pneumonitis- RBILD Respiratory Bronchiolitis Interstitial Lung Disease- DIP Desquamative Interstitial Pneumonia- COP Cryptogenic Organizing Pneumonia- AIP Acute Interstitial Pneumonia

Rare IIPs- Idiopathic Lymphoid Interstitial Pneumonia- Idiopathic pleuroparenchymal fibroelastosis

Unclassifiable Interstitial Pneumonias

Interstitial Lung Disease

Rare ILDsLAM, PLHC, etc

Sarcoidosis

ILDs of known cause

Collagen Vascular DiseaseSclerodermaRheumatoid Arthritis

Organic Exposures(Hypersensitivity Pneumonitis)Farmer’s LungBird Fancier’s Lung

Inorganic ExposuresAsbestosisSilicosis

IatrogenicNitrofurantoinRadiationChemotherapy

Find the Panda

Find the Panda

Idiopathic Interstitial

Pneumonias

Major IIPs- IPF Idiopathic Pulmonary Fibrosis- iNSIP Idiopathic Nonspecific Interstitial Pneumonitis- RBILD Respiratory Bronchiolitis Interstitial Lung Disease- DIP Desquamative Interstitial Pneumonia- COP Cryptogenic Organizing Pneumonia- AIP Acute Interstitial Pneumonia

Rare IIPs- Idiopathic Lymphoid Interstitial Pneumonia- Idiopathic pleuroparenchymal fibroelastosis

Unclassifiable Interstitial Pneumonias

Interstitial Lung Disease

Rare ILDsLAM, PLHC, etc

Sarcoidosis

ILDs of known cause

Collagen Vascular DiseaseSclerodermaRheumatoid Arthritis

Organic Exposures(Hypersensitivity Pneumonitis)Farmer’s LungBird Fancier’s Lung

Inorganic ExposuresAsbestosisSilicosis

IatrogenicNitrofurantoinRadiationChemotherapy

Inspiratory Crackles(clubbing)

CXR PFTs

Cough / Dyspnea

Interstitial Lung Disease

Inspiratory Crackles(clubbing)

CXR PFTs

Cough / Dyspnea

Interstitial Lung Disease

Refer to Respirology

Inspiratory Crackles(clubbing)

CXR PFTs

Cough / Dyspnea

Interstitial Lung Disease

CT ChestHRCT images

Basic Bloodwork

Serology:ANA, RF, anti-CCP

For some patients:• Bronchoscopy/BAL• Surgical Lung Biopsy• Rheumatology opinion

Inspiratory Crackles(clubbing)

CXR PFTs

Cough / Dyspnea

CT ChestHRCT images

Basic Bloodwork

Serology:ANA, RF, anti-CCP ILD Multidisciplinary

Discussion

Diagnosis

Management

56 male ex-smoker Control systems

engineer

PMHx: GERD (PPI)

3 year history: Exertional dyspnea

(stairs) Exertional cough

Am Fam Physician. 1998 Sep 15;58(4):935-944

Occupational history

Control Systems Engineer x 25 years Inspecting and servicing

pressure gauges x 7 yrs Administrator x 18 yrs Bystander asbestos

exposure

Heavy construction as a machine operator (dusts)

Other exposures

Raised on a farm in AB Mixed: livestock & crops Canola, barley 1500 hogs 360 cattle Small chicken coop

Clean grain bins, attending animals

Coal-burning stove

Other exposures

Pet cockatiel x 5 yrs

No down bedding or other feather products

No mold No hot tubs

71 male ex-smoker CAD, RCA infarct, R

sided heart failure Hypertrophic

cardiomyopathy & LV systolic dysfunction

Custodian commercial buildings

Occupational history

High-pressure welding late teens (no mask)

Automobile manufacturing: “wet deck” sanding area; near “dry deck”

Gunsmith Commercial cleaner Short haul trucking Taxi driver Union representative

• Do you get rashes? Where? • Do you have dry, gritty

eyes?• Do you have a dry mouth?

Do you get sores in your mouth? What about cavities/infections?

• Do you have pain or swelling in the small joints of your hands/fingers? Where?

• Do you have pain in your muscles? Are you able to wash your hair? Get up from a chair?

• Do you have acid reflux? Problems swallowing?

• Do you have numbness or tingling in your hands/feet, arms or legs?

• Is your skin tight? Are you having trouble opening your mouth?

• Do you get sores on the tips of your fingers?

• Do your fingers get cold and change colour?

Screening questions for features of Autoimmune Disease*

* Not intended to replace a formal Rheumatology opinion!

Screening physical exam for features of Autoimmune Disease

Hinchcliff, M, and Varga, J. Am Fam Physician. 2008 Oct 15;78(8):961-968

http://www.medicinenet.com/rheumatoid_arthritis_early_symptoms/article.htm

https://www.aoedemuse.com/2012/02/22/dermatowhat-on-living-with-dm/

http://sclerodermainfo.org/faq/symptoms-and-prognosis/

http://online.cit.edu.au/fitnessonline/fit_tb/fit011_1_lr10/fit011_1_lr10_1_1.htm

• Skin thickening• Upper extremity strength• Serositis• Pulmonary Hypertension

* Not intended to replace a formal Rheumatology opinion!

Screening Serology

When there are no signs/symptoms of autoimmune disease:

• ANA, RF, anti-CCP antibodiesWith signs/symptoms of autoimmune disease:

(Testing should be based on suspected disease)

Autoantibody Association

dsDNA Highly specific for SLE

SS-A (anti-Ro) SLE, Sjogren’s Syndrome

SS-B (anti-La) Sjogren’s Syndrome

Scl-70 Scleroderma, especially with ILD

RF, anti-CCP Rheumatoid arthritis

RNP MCTD

Jo-1, EJ, PL7, PL12, OJ DM/PM, anti-synthetase antibody syndrome

Antin-Ozerkis, D et al. in Interstitial Lung Disease. Elsevier. 2017

At the end of this workshop you’ll be able to:

• Develop an approach to diagnose and classify ILD.• Screen patients for environmental and

occupational causes of ILD.• (Screen patients for rheumatological causes of

ILD).Discuss recent updates in anti-fibrotic therapy.

Objectives

Slide courtesy of Dr. M KolbSivakumar P et al, Curr Opinion Pulm Med 2012

IPF – Molecular Drug Targets

Slide courtesy of Dr. M KolbSivakumar P et al, Curr Opinion Pulm Med 2012

NINT

NN

N

N

PIRFP

PP

P

PP P

“broad”

“precise”

IPF – Molecular Drug Targets

“ASCEND”King TE Jr et al. N Engl J Med 2014. DOI: 10.1056/NEJMoa1402582

Pirfenidone (Esbriet)

Form: 267 mg capsule Dose: 3 capsules three times daily (with meals)

Important Side Effects: Upset stomach, nausea, decreased appetite

— Take pirfenidone with food Photosensitive rash

— Sunblock with SPF 50 daily Hepatoxicity (liver damage)

— Regular bloodwork— Reversible with dose reduction / discontinuation

ASCEND Primary and Key Secondary Outcomes

King TE Jr et al. N Engl J Med 2014. DOI: 10.1056/NEJMoa1402582

“INPULSIS”Richeldi L et al. N Engl J Med 2014. DOI: 10.1056/NEJMoa1402584

Form: 150 mg capsule + 100 mg capsule Dose: one 150 mg capsule twice per day with

meals

Important Side Effects: Diarrhea

— Loperamide (Imodium) capsules Nausea, vomiting Hepatoxicity (liver damage)

— Regular bloodwork— Reversible with dose reduction / discontinuation

Nintedanib (Ofev)

INPULSIS Primary Outcome

Richeldi L et al. N Engl J Med 2014. DOI: 10.1056/NEJMoa1402584

Key message on anti-fibrotics:

They do not stop IPF from getting worse They do not reverse existing pulmonary fibrosis They slow down the rate of disease progression

Side effects are tolerated by most but unbearable for a few

$46,000 per year/patient

Completed therapy: 34 42

Summary

A complete history, including a detailed occupational and exposure history, is key in narrowing the differential diagnosis for ILD.

Pirfenidone and nintedanib are the only anti-fibrotic agents approved for use in mild to moderate IPF in Canada— Combination therapy has not been shown to be

effective and is not recommended

Thank You!