Disclosures
All relevant financial relationships with commercial interests
reported by faculty speakers, steering committee members,
non-faculty content contributors and/or reviewers, or their
spouses/partners have been listed in your program syllabus.
Off-label Discussion Disclosure
This educational activity may contain discussion of published and/or
investigational uses of agents that are not indicated by the Food and Drug
Administration. PCME does not recommend the use of any agent outside of
the labeled indications. Please refer to the official prescribing information for
each product for discussion of approved indications, contraindications and
warnings. The opinions expressed are those of the presenters and are not to
be construed as those of the publisher or grantors.
Pre-activity Survey
• Please take out the Pre-activity Survey from the
front of your packet
• Your answers are important to us and will be used
to help shape future CME activities
Polling Question
Pre-activity Survey
Please rate your level of confidence in developing treatment
strategies for patients with idiopathic pulmonary fibrosis
(IPF):
A. Not confident
B. Slightly confident
C. Confident
D. Very confident
E. Expert
Polling Question
Pre-activity Survey
How familiar are you with treatment recommendations for
IPF?
A. Not familiar
B. Slightly familiar
C. Familiar
D. Very familiar
E. Expert
Polling Question
Pre-activity Survey
JG is a 67-year-old white female who presents to her physician with
worsening shortness of breath on exertion and non-productive cough
not relieved by over-the-counter antihistamines or cough
suppressants.
Which of the following is NOT a “red flag” for additional
evaluation for IPF:
A. Velcro crackles
B. Presence of GERD
C. Presence of OSA
D. Exposure to environmental toxins
Polling Question
Pre-activity Survey
JG has a history of gastroesophageal reflux disease (GERD), for
which she takes omeprazole once daily, and obstructive sleep apnea
(OSA) treated with nasal continuous positive airway pressure at night.
Physical exam is notable for bibasilar fine crackles that sound like
Velcro being separated.
What is the most appropriate initial diagnostic test to identify
IPF and rule out other conditions?
A. Pulmonary function testing
B. Chest x-ray
C. High-resolution computed tomography
D. Open lung biopsy
Polling Question
Pre-activity Survey
JG is diagnosed with IPF.
Which of the following factors has been associated with
prolonged survival and improved quality of life?
A. Lung biopsy
B. Aerobic exercise
C. Corticosteroids
D. Multidisciplinary care at specialized treatment center
Polling Question
Pre-activity Survey
Which of the following medications has been shown to
reduce the risks of death or disease progression in patients
with IPF?
A. Prednisone
B. N-acetylcysteine
C. Pirfenidone
D. Nintedanib
Polling Question
Pre-activity Survey
Which of the following medications has been shown to
reduce the risk for acute exacerbations of IPF?
A. Prednisone
B. N-acetylcysteine
C. Pirfenidone
D. Nintedanib
Learning Objectives
At the conclusion of this activity, participants should be able to
demonstrate the ability to:
• Screen patients presenting with shortness of breath and other
risk factors for pulmonary fibrosis and differentiate idiopathic
from non-idiopathic forms by applying appropriate diagnostic
testing, such as high-resolution CT scanning, to characterize
distribution of fibrosis and inflammation
• Incorporate current guidelines and new clinical evidence to
develop an appropriate management plan for patients with IPF
• Describe strategies to engage patients and facilitate a
multidisciplinary approach to the management of IPF and
associated comorbidities
An Exciting Time in IPF
• Guidelines to standardize the definitions
• Networks developing across the US
• Patient support resources expanding
• Registries established
• New treatment options
A Challenging Time in IPF
• Making the right diagnosis
of IPF is more critical than
ever
• Patients often see multiple
doctors prior to diagnosis
• Delayed referral to tertiary
care center associated
with mortality
Survival from the time of evaluation at a tertiary care center
adjusted for age and FVC across quartiles of delay. Entry
time into the cohort began at study enrollment.
Making the IPF Diagnosis is Hard
• There are more than 200 recognized types of diffuse
parenchymal lung diseases
• While IPF is the most
common, there are
many “look alike”
diseases
• History, symptoms,
physical exam,
imaging, and
sometimes histology
are required to make
the IPF diagnosis
Mueller-Mang C et al. Radiographics. 2007;27:595-615.
Screening Patients for IPF
• Common first symptoms: dyspnea on exertion, cough
– Symptoms may be present years before diagnosis
•
Registry data suggest 3.9 ± 4.4 years
• Age >50
• Male predominance
• Consider occupational, environmental, and drug
exposures, along with autoimmune disease symptoms that
may point to another diagnosis
• Consider risk factors associated with IPF
Risk Factors Associated with IPF
• History of cigarette smoking
• Environmental exposures
– Recent registry report with 27% of IPF patients reporting an
enviromental exposure
• Gastroesophageal reflux disease (GERD)
• Genetics
• Infections
Patient 1 Case Study
• CC: Shortness of Breath (SOB), Post-hospital Discharge Evaluation
• HPI: Patient 1 is a 63-year-old man who presents for outpatient
pulmonary evaluation of an abnormal chest x-ray found during recent
hospitalization.
• One week prior to his office visit, patient 1 was admitted to a local
hospital with a diagnosis of atypical community acquired pneumonia,
treated with 7 days of levofloxacin therapy, and discharged to home
with supplemental oxygen. Patient notes admissions for pneumonia
2 previous times over the past 3 years and has noticed increasing
dyspnea with exertion.
• Other concerns during evaluation are nonproductive cough (which
he attributes to sinus congestion), general fatigue, and heart burn.
Case 1 (continued)
PMH: Osteoarthritis, GERD, and macular degeneration
Medications: Ranitidine OTC and levofloxacin 500 mg daily for one
week
Allergies: NKDA
FH: No history of lung disease, no heart disease, no malignancies
Social History: Patient 1 is a previous smoker (1/2 ppd for 18 years)
and stopped smoking after he left the Navy. He served in the Navy for
12 years. No overseas tours of duty noted.
He worked at an office and does not recall any exposures. He is
married with one daughter. He was originally from Chicago, IL and
moved to Florida in his 30s. He has a family dog. No recent travel
noted.
Case 1 (continued)
Physical Exam
T: 97.6 P: 82 BP: 116/60 RR: 16 Sat: 98% on 2L Ht: 65 in Wt: 165 lbs
Gen: Well developed, well nourished, not in distress
Neck: No lymphadenopathy, no bruits
CV: RRR, no murmur, rubs, no gallops
Lungs: Clear anteriorly without wheeze, bibasilar inspiratory and expiratory dry crackles
Abd: soft/non-tender
Ext: No clubbing noted and no cyanosis noted, mild edema at ankles
Neuro: Alert and oriented x3, non-focal; ambulating with portable oxygen E tank today
Labs:
 Normal chemistries and renal function
 CBC WNL without eosinophila, normal diff
 Serologies normal rheum panel, normal immunoglobulins
Case 1 (continued)
• CXRs: bibasilar interstitial infiltrates (R>L), no
effusions, no pulmonary edema, no adenopathy;
review of exams (back 3 years) with progressive
interstitial changes mid-lung and basilar
• Echo: EF 50%, normal valves, PA est. 60 mmHg
• HRCT: bilateral ground-glass opacities and reticular
changes with subpleural and lower lobe predominance
• Select PFT Data 2 weeks after initial visit:
FVC
59%
TLC
61%
DLco
40%
Diagnostic Tools
• Symptoms
• Exam: inspiratory basilar “velcro” crackles, clubbing
• Serologies for connective tissue disorders
• Pulmonary function testing with restrictive pattern, though
may be normal in early stages
• HRCT
• Histology of lung biopsy (not always needed)
HRCT of the Chest
High-Resolution Computed Tomography Criteria for UIP Pattern
UIP Pattern
Possible UIP Pattern
Inconsistent with UIP Pattern
(All 4 Features)
(All 3 Features)
(Any of the 7 Features)
• Subpleural, basal
Predominance
• Subpleural, basal
Predominance
• Upper or mid-lung predominance
• Reticular abnormality
• Reticular abnormality
• Honeycombing with or
without traction
bronchiectasis
• Absence of features listed as
inconsistent with UIP pattern
(see third column)
• Absence of features
listed as inconsistent
with UIP pattern
(see third column)
• Peribronchovascular predominance
• Extensive ground glass abnormality
(extent > reticular abnormality)
• Profuse micronodules (bilateral,
predominantly upper lobes)
• Discrete cysts (multiple, bilateral, away
from areas of honeycombing)
• Diffuse mosaic attenuation/air-trapping
(bilateral, in three or more lobes)
• Consolidation in bronchopulmonary
segment(s) lobe(s)
UIP = usual interstitial pneumonia
HRCT Honeycombing and Opacity
Mueller-Mang C et al. Radiographics. 2007;27:595-615.
HRCT Heterogeneous Fibrotic and
Normal Lung Tissue
Mueller-Mang C et al. Radiographics. 2007;27:595-615.
Histology
UIP pattern
(All Four Criteria)
Probable UIP Pattern
• Evidence of marked
fibrosis/architectural
distortion, ±
honeycombing in a
predominantly
subpleural/paraseptal
distribution
• Evidence of fibrosis
architectural distortion, ±
honeycombing
• Presence of patchy
involvement of lung
parenchyma by fibrosis
• Absence of features
against diagnosis of UIP
suggesting an alternate
diagnosis (see fourth
column)
• Presence of fibroblast foci
• Absence of features
against a diagnosis of UIP
suggestion an alternate
diagnosis (see fourth
column)
• Absence of either patchy
involvement of fibroblastic
foci, but not both
OR
• Honeycomb changes
only‡
Possible UIP Pattern
(All Three Criteria)
• Patchy or diffuse
involvement of lung
parenchyma by fibrosis,
with or without interstitial
inflammation.
• Absence of other criteria
for UIP (see UIP Pattern
column)
• Absence of features
against a diagnosis of
UIP suggesting an
alternate diagnosis (see
fourth column)
Not UIP Pattern
(Any of the Six Criteria)
• Hyaline membranes*
• Organizing pneumonia*†
• Granulomas†
• Marked interstitial
inflammatory cell infiltrate
away from honeycombing
• Predominant airway
centered changes
• Other features suggestive
of an alternate diagnosis
HRCT = high-resolution computed tomography; UIP = usual interstitial pneumonia
* Can be associated with acute exacerbation of idiopathic pulmonary fibrosis.
†
An isolated or occasional granuloma and/or a mild component of organizing pneumonia pattern may rarely be coexisting in
lung biopsies with an otherwise UIP pattern.
‡
This scenario usually represents end-stage fibrotic lung disease where honeycombed segments have been samples but
where a UIP pattern might be present in other areas. Such areas are usually represented by overt honeycombing on HRCT
and can be avoided by pre-operative targeting of biopsy sites away from these areas using HRCT.
Follow Up on Case 1
• Patient 1 had rapidly progressive course after routine follow up. Hospitalized 2
more times during the year with worsening hypoxemia and increased oxygen
needs requiring 5L continuous to maintain saturations of 92% at rest.
• A referral was placed to the lung transplant service and patient 1 started on
prednisone 60 mg daily during the first hospitalization and titrated down to a daily
dose of 15 mg daily.
• Hospitalized again within 3 months due to chest pain; during second
hospitalization a right- and left-heart catheterization confirmed secondary PH and
no coronary disease. Started on nintedanib 100 mg, twice daily at discharge. Seen
by transplant team 2 weeks after discharge and awaiting completion of work up
• One week after transplant service evaluation, family took patient 1 to the hospital
due to an inability to obtain oxygen saturations above 86% on 6L. He was
intubated and hospitalized for 2 weeks on a ventilator with an inability to wean from
support due to persistent hypoxemia. He expired in hospice care due to hypoxic
respiratory failure.
Making a Differential Diagnosis:
Patient 2 Case Study
• CC: Recurrent Pneumonia
• HPI: Patient 2 is a 74-year-old woman with 2 episodes of pneumonia
treated by antibiotic in the past 6 months. First chest x-ray diagnosed
RLL pneumonia; treated with azithromycin for 5 days and she felt
better after the course of treatment.
• Two months later, had recurrent fever and cough. Chest CT
demonstrated atypical infiltration of the RLL and she was treated for
10 days with levofloxacin 750 mg. In her presentation she denied
muscle or joint pain. Increased lethargy and fatigue, progressively
worse since the first pneumonia. No chest pain or discomfort noted.
She did still complain of productive cough without wheezing.
Case 2 (continued)
PMH: GERD, hypercholesterolemia, and hypertension
Medications: Amlodipine 10 mg daily, HcTZ 12.5 mg daily, simvastatin 40 mg at
bedtime, and esomeprazole 20 mg daily
Allergies: none reported
FH: CAD
Social History: She is a previous smoker (40 pack years) and stopped 10 years prior
to visit. When asked about work or exposure, she notes she is a retired administrator
without specific exposures.
ROS: negative
PE: T: 97 P: 84 BP: 128/62 Sat: 94% on RA Wt: 147 lbs
Gen: Healthy appearing
CV: RRR, no G
Chest: Clear bilaterally without wheeze or crackle
Abd: Soft +BS wnl
Ext: No cyanosis, no clubbing
Neuro: Alert and oriented x3
Case 2 (continued)
Radiology: HRCT with mild subpleural cystic changes bilaterally in the mid-lung to
lower lung fields with diffuse ground glass opacities noted bibasilarly
Course: Patient 2 was treated with prednisone at 40 mg daily for 2 weeks and
tapered off over an additional 2 weeks; HRCT was repeated 2 months after
completion of her steroid taper.
CT scan demonstrated mild basilar fibrotic changes without ground glass opacities
and stability in the previously seen subpleural cystic changes.
Her repeat PFTs one year after initial evaluation demonstrates stability in her FVC
with only a 7% change from initial presentation spirometry. She remains with minimal
cough as her primary complaint and no longer has limiting shortness of breath on
exertion. No exposures were found after careful review of her environment and travel
history and UIP is not believed to be the diagnosis of fibrosing lung pathology.
MH
First PFT
Second PFT
FEV1
1.70 (81%)
1.40 (67%)
FVC
2.17 (78%)
1.97 (71%)
FEV1/ FVC
0.78
0.71
When To Do A Lung Biopsy?
Histologic confirmation should be obtained in all patients with
atypical imaging findings, such as extensive ground-glass
opacities, nodules, consolidation, or a predominantly
peribronchovascular distribution
When NOT To Do A Lung Biopsy?
Surgical lung biopsy is the gold standard method of
diagnosing IPF, but carries risks that should be discussed
prior to the procedure. Risks include infection, bleeding,
pneumothorax, persistent air leak into the chest cavity, and
as with all surgical procedures, risk of death in 3%-4% of
cases within 30 days of biopsy
Histology-IPF vs NSIP
UIP
NSIP
Mueller-Mang C et al. Radiographics. 2007;27:595-615.
Putting It All Together
Suspected IPF
Identifiable causes for ILD?
Yes
No
HRCT
Possible UIP
Inconsistent w/UIP
Surgical Lung
Biopsy
Not UIP
UIP
Probable UIP/Possible UIP
Non-classifiable fibrosis
MDD
IPF
IPF/Not IPF
Not IPF
Comorbidities of Idiopathic
Pulmonary Fibrosis
Comorbidities in IPF
•
•
•
•
•
•
•
•
•
•
GERD
CAD
OSA
Pulmonary hypertension
Pulmonary embolism
Emphysema
Obesity
Diabetes mellitus
Osteoporosis
Cachexia
• Depression and anxiety
Aging
• Loss of 20-30 mL vital capacity per year
– Loss of 1900 mL by age 85
• Other causes of reduced lung volumes in an aging population
– Kyphosis/scoliosis
– CHF with an enlarged heart
– Deconditioning
– Neuromuscular disease
– Metabolic disease
– Obesity
Sharma G, Goodwin J. Clin Interv Aging. 2006;1:253-260.
Obesity
Physiologic Effects:
Endocrine Effects:
• Restriction
• Adipose tissue
• Decreased airway size
• Hormonal effects
• Compromised chest muscle
function
– reduced respiratory muscle
and diaphragm endurance
• Altered lung perfusion and
VQ mismatch at bases
• Upper airway narrowing
Salome CM et al. J Appl Physiol (1985). 2010;108:206-211.
– *Leptin: promotes visceral
fat deposition
• Proinflammatory
– *TNF alpha: promotes
• Pharyngeal neuromuscular
dysfunction
GERD in IPF
Lee JS et al. Am J Med. 2010;123:304-311.
Prevalence of GERD
• Normal prevalence:
10%-20%
• Prevalence of GERD in
COPD: 60%
• Prevalence of GERD in
cystic fibrosis: 35%-81%
• Prevalence of GERD in
asthma: 68%
• Prevalence in IPF: 90%
Prevalence
113%
90%
68%
45%
23%
0%
in general
population
in COPD
in Cystic
Fibrosis
in Asthma
in IPF
Survival Distribution Function
Therapy for GERD is Associated with
Improved Survival
Time to Event (days)
Lee JS et al. Am J Respir Crit Care Med. 2011;184:1390-1394.
IPF With Severe PH
mPAP = 61 mmHg
Prevalence of PH in IPF
Hamada (2007)
RHC
Echo
Raghu (2010)
Patel (2007)
Song (2009)
Nathan (2007)
Zisman (2007)
Shorr (2007)
Minai (2009)
Nadrous (2005)
Nathan (2008)
at evaluation
at transplantation
Estimate of PH Prevalence, %
Nathan SD, Cottin V. Eur Respir Monogr. 2012;57:148-160.
ATS/ERS Recommendation
• PH should not be treated in the majority of patients with IPF,
but treatment may be a reasonable choice in a minority
(weak recommendation, very low-quality evidence).
• In patients with moderate to severe PH (mPAP >35 mmHg)
documented by right heart catheterization, a trial of
vasomodulatory therapy may be indicated.
• It is not clear if IPF with PH represents a distinct clinical
phenotype (IPF–PH).
Raghu G et al. Am J Respir Crit Care Med. 2011;183:788-824.
Why Refer Early to an ILD Center?
• Diagnostic expertise
– Standardized assessment
– Confirmation of diagnosis
• Management expertise
–
–
–
–
–
–
Choice of an appropriate therapy
Oxygen prescription
Pulmonary rehabilitation
Attention to obesity and sarcopenia/frailty
Potential enrollment in a clinical trial
Transplant evaluation
Flaherty KR et al. Am J Respir Crit Care Med. 2004;170:904-910.
Flaherty KR et al. Am J Respir Crit Care Med. 2007;175:1054-1060.
Lamas DJ et al. Am J Respir Crit Care Med. 2011;184:842-847.
Maintain Recreational Activities
• Normalcy should be maintained as much as possible
• Regular activities give rhythm to life
• Low intensity activities enhance pleasure and social contact
– Socializing
– Cultural activities
– Family events
– Sexual activity
– Exercise
Pulmonary Rehabilitation
• Program originally designed for COPD
• Education, exercise, support/counseling
• Run by PT/RT
• Goals:
– Improve self-management
– Reduce symptoms
– Optimize functional capacity
– Increase social participation
Holland AE et al. Thorax. 2008;63:549-554.
Monitoring for Disease Progression
• Every 3 to 6 months:
– PFTs
– 6MWT (distance/nadir saturation)
– O2 requirement
– Comorbidities
– Consider dyspnea questionnaire (UCSD)
• HRCT
– Annually or when suspicion for clinical worsening
Lung Transplantation for IPF:
2014 Referral Guidelines
• Histopathologic or radiographic evidence of usual
interstitial pneumonitis (UIP)
• Abnormal lung function: FVC <80% predicted or
DLCO <40% predicted
• Any dyspnea or functional limitation attributable to lung
disease
• Any oxygen requirement, even if only during exertion
Weill D et al. J Heart Lung Transplant. 2015;34:1-15.
Oxygen Therapy
• Goal: Maintain SpO2 >89%
– Rest, activity, sleep
• Give patients control over their
disease
• Make sure patients are using
O2 correctly
• Regular assessment
– Yearly (or with change in status), nocturnal oximetry,
exercise oximetry (q3 months)
• Pulse oxygen does not generally supply enough O2 in
IPF patients to fulfill their exertional O2 needs
Nishiyama O et al. Respir Med. 2013;107:1241-1246.
Risk Factor Reduction
• Smoking cessation
• Weight management
• Sleep study
• Exercise training/pulmonary rehab
• Screen and address comorbidities
– GERD
– OSA
– Heart disease (diastolic dysfunction/PH/CAD)
– Thromboembolic disease
Patient Care Summary
• Educate patients
– Refer to reliable sources
• Prescribe O2
– (screen for resting/nocturnal/exertional requirement)
• Prescribe medication
• Look for treatable comorbid conditions
• Refer
– Pulmonary rehab
– ILD center
– Lung transplantation evaluation
• Monitor for disease progression
Patient Resources
• INSPIRE support groups
– https://www.inspire.com/conditions/pulmonary-fibrosis
• Pulmonary Fibrosis Physician Blogs
– Jeff Swigris: www.pulmonaryfibrosisresearch.org/blog
– David Lederer: PFDoc.org
• Local support groups
• Online resources
– www.patientslikeme.com
– www.coalitionforpf.org
– www.pulmonaryfibrosis.org
– www.lungsandyou.com
– www.knowIPFnow.com
New Agents for the
Management of IPF
Past Negative Clinical Trials in IPF
Trial
n
Primary Endpoint
Result
Interferon-beta (1999)
167
Progression-free survival time
Negative
Interferon-gamma (GIPF-001)
330
Progression-free survival
Negative
Interferon-gamma (Inspire)
826
Survival time
Negative
Pirfenidone (CAPACITY 1)
344
Change in FVC
Negative
Etanercept
100
Change in DLco, FVC
Negative
Imatinib Mesylate
120
Progression-free survival
Negative
Bosentan (BUILD 1 and 2)
132
Change in 6MW
Negative
Bosentan (BUILD 3)
390
Progression-free survival time
Negative
Sildenafil (STEP)
29
Change in 6MWD, Borg
dyspnea index
Negative
Ambrisentan (Artemis-IPF)
478
Progression-free survival
Stopped –
Ambrisentan (Artemis-PH)
50
6MWD
Stopped –
Everolimus
89
Progression
Negative
Noth I et al. Am J Respir Crit Care Med. 2012;186:88-95.
Pirfenidone
• Pirfenidone is an orally-available small molecule that exerts systemic
antifibrotic effects
• Pirfenidone is active in several animal models of fibrosis
– Including lung, liver, heart, and kidney
– Active at clinically relevant exposures
• The molecular target of pirfenidone is not known; however,
preclinical evidence of antifibrotic activity exists
– Both antifibrotic and anti-inflammatory activities in vivo and in vitro
– Modulates extracellular matrix deposition, production of cytokines and
growth factors, and fibroblast proliferation
Inclusion Criteria
• Age 40-80 years
• Confident diagnosis of IPF based on central
review of HRCT +/- SLB
• Percent predicted FVC ≥50% and ≤90%
• Percent predicted DLco ≥30% and ≤90%
• FEV1/FVC ratio ≥0.80
• 6MWD ≥150 m
King TE Jr. et al. N Engl J Med. 2014;370:2083-2092.
Patient Characteristics
Pirfenidone
(n=278)
Placebo
(n=277)
Age (years)
69.0
68.0
Male gender (%)
79.9
76.9
US enrollment (%)
67.3
66.4
FVC (% predicted)
68.1
68.0
DLco (% predicted)
41.5
43.0
6MWT distance (m)
409.3
423.0
FEV1/FVC ratio
0.84
0.84
Supplemental O2 use (%)
28.1
27.4
Time since IPF diagnosis (years)
1.7
1.7
Former Smoker (%)
66.2
61.0
HRCT “Definite IPF” (%)
95.7
94.6
Surgical lung biopsy (%)
30.9
28.5
King TE Jr. et al. N Engl J Med. 2014;370:2083-2092.
Decreased FVC or Death with Pirfenidone
King TE Jr. et al. N Engl J Med. 2014;370:2083-2092.
Pirfenidone Reduces Loss of FVC
King TE Jr. et al. N Engl J Med. 2014;370:2083-2092.
Pirfenidone Patients Maintain Walk
Distance or Survive
King TE Jr. et al. N Engl J Med. 2014;370:2083-2092.
Increased Progression Free Survival
with Pirfenidone
King TE Jr. et al. N Engl J Med. 2014;370:2083-2092.
Pirfenidone Associated with Less Mortality
King TE Jr. et al. N Engl J Med. 2014;370:2083-2092.
Conclusions
• Pirfenidone decreases the decline in breathing
tests over 52 weeks
• Pirfenidone appears to have a benefit in terms of
risk of death
• Pirfenidone appears to be well tolerated
Nintedanib
• Nintedanib is an orally-available intracellular inhibitor that
targets multiple tyrosine kinases, including:
– VEGF receptors
– FGF receptors
– PDGF receptors
Richeldi L et al. N Engl J Med. 2014;370:2071-2082.
Inclusion Criteria
• Age ≥40 years
• Diagnosis of IPF within previous 5 years
• IPF diagnosis based on central review of HCRT and lung
biopsy, if available
• Percent predicted FVC ≥50%
• Percent predicted DLco 30%–79%
Richeldi L et al. N Engl J Med. 2014;370:2071-2082.
Nintedanib
Impulsis-2
Impulsis-1
• 718 Screened
• 794 Screened
• 616 Randomized
• 551 Randomized
• 513 Treated
• 548 Treated
10: ΔFVC
1066 Patients
Richeldi L et al. N Engl J Med. 2014;370:2071-2082.
52 Weeks
20: Time to first AE
Δ SGRQ
Baseline Patient Characteristics
Richeldi L et al. N Engl J Med. 2014;370:2071-2082.
Nintedanib Reduces Loss of FVC
Richeldi L et al. N Engl J Med. 2014;370:2071-2082.
Nintedanib Reduces Loss of FVC
Richeldi L et al. N Engl J Med. 2014;370:2071-2082.
Time to Acute Exacerbations Delayed with
Nintedanib
Richeldi L et al. N Engl J Med. 2014;370:2071-2082.
Conclusions
• Nintedanib decreases the decline in breathing tests over
52 weeks
• There was no detectable difference in mortality over 52
weeks
• Nintedanib appears to be well tolerated
Future Therapies
• Better stratification of IPF patients
– CCL 18 data and risk for death
– Loxyl-2 and composite endpoint
– HSP 80 and acute exacerbation
• Combination therapy?
• IPF registries and further research
Participant CME Evaluation
• Please take out the Participant CME Post-survey and
Evaluation Form from the back of your packet.
• If you are not seeking credit, we ask that you fill out the
information pertaining to your degree and specialty, as well
as the few post-activity survey questions measuring the
knowledge and competence you have garnered from this
program. The post-survey begins on page 1 of the
evaluation form.
• Your participation will help shape future CME activities.
Polling Question
Post-activity Survey
Please rate your level of confidence in developing treatment
strategies for patients with idiopathic pulmonary fibrosis
(IPF):
A. Not confident
B. Slightly confident
C. Confident
D. Very confident
E. Expert
Polling Question
Post-activity Survey
How familiar are you with treatment recommendations for
IPF?
A. Not familiar
B. Slightly familiar
C. Familiar
D. Very familiar
E. Expert
Polling Question
Post-activity Survey
JG is a 67-year-old white female who presents to her physician with
worsening shortness of breath on exertion and non-productive cough
not relieved by over-the-counter antihistamines or cough
suppressants.
Which of the following is NOT a “red flag” for additional
evaluation for IPF:
A. Velcro crackles
B. Presence of GERD
C. Presence of OSA
D. Exposure to environmental toxins
Polling Question
Post-activity Survey
JG has a history of gastroesophageal reflux disease (GERD), for
which she takes omeprazole once daily, and obstructive sleep apnea
(OSA) treated with nasal continuous positive airway pressure at night.
Physical exam is notable for bibasilar fine crackles that sound like
Velcro being separated.
What is the most appropriate initial diagnostic test to identify
IPF and rule out other conditions?
A. Pulmonary function testing
B. Chest x-ray
C. High-resolution computed tomography
D. Open lung biopsy
Polling Question
Post-activity Survey
JG is diagnosed with IPF.
Which of the following factors has been associated with
prolonged survival and improved quality of life?
A. Lung biopsy
B. Aerobic exercise
C. Corticosteroids
D. Multidisciplinary care at specialized treatment center
Polling Question
Post-activity Survey
Which of the following medications has been shown to
reduce the risks of death or disease progression in patients
with IPF?
A. Prednisone
B. N-acetylcysteine
C. Pirfenidone
D. Nintedanib
Polling Question
Post-activity Survey
Which of the following medications has been shown to
reduce the risk for acute exacerbations of IPF?
A. Prednisone
B. N-acetylcysteine
C. Pirfenidone
D. Nintedanib