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!