Idiopathic Pulmonary Fibrosis:
Diagnosis, Treatment, and
Management
ISCHR Conference March 5, 2016
Wendi R Mason, MSN, ACNP-BC
Program Director
Interstitial Lung Disease Program at Vanderbilt
Idiopathic Pulmonary Fibrosis
A specific form of chronic, progressive fibrosing interstitial
pneumonia of unknown cause, occurring primarily in older
adults, limited to the lungs, and associated with the
histopathologic and or radiologic pattern of UIP.
Symptom onset to diagnosis is 1.5 years
Diagnosis to death is 3.8 years
Case Study: JWM
• 67 year old WM presented in early 2014 for shortness of
breath concerning for IPF.
Earlier had been dx’d with COPD and given inhalers
More recently, had CT and nondiagnostic bronch
Referred to our Center
• Symptoms: shortness of breath with exertion; rare cough
• ROS:
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EENT: glasses, no dysphagia, + snores
Card: no chest pain or pressure
GI: reflux with OTC tums for relief
Musculoskel: OA in right shoulder, right knee; no clubbing;
Derm: no rash
IPF: Clinical Presentation
Consider IPF in all adults with unexplained chronic exertional
dyspnea which commonly presents with cough, bilateral
crackles, and finger clubbing.
Incidence increases with older age with typical presentation
between 60 and 70 years old. A presentation younger than 50
years may be familial in nature.
Slightly more men than women.
Estimated 130,000 persons in the US with IPF, with about 40,000
cases diagnosed annually.
JWM: Past Medical History
GERD
HTN
Hyperlipidemia
Obesity (BMI 35.4)
Medications:
• Coricidin prn
• TUMS prn
No macrodantin, bleomycin
Reivew of outside records:
CT chest – patchy areas of subpleural increased reticulation, suggestion of
bronchiolectasis versus less likely early honeycombing, suggestion of ground
glass opacities; distribution is subpleural with lower lung zone involvement.
Concern for NSIP, less likely UIP, collagen-vascular disease vs HP vs. infection.
Transbronchial biopsy – neg for tumor
IPF: Comorbidities
Gastroesophageal Reflux Disease (GERD)
Obstructive Sleep Apnea (OSA)
Pulmonary Arterial Hypertension (PAH)
Coronary Artery Disease (CAD)
Hypothyroidism
Obesity
Emphysema
JWM: Social History
Retired cement plant employee of 40+ years
Started out doing repairs on machines, advanced to safety and
training; usually wore masks and had abbreviated exposure to
asbestos in walls.
Currently drives a van locally
EtOH – 1-2 beers a week
No h/o illicit drugs
Cigarette use for 2 weeks in high school
Pets: 3 dogs, no birds
Hobbies: races cars, rides motorcycles
IPF: Risks
Although by definition, IPF is a disease of unknown etiology,
there are a number of risk factors:
cigarette smoking (20+ pack years)
environmental exposures (wood dust, metal dusts)
certain viruses (EBV, CMV, HHV)
GERD (acid and alkaline GER)
familial
JWM: Family History
Father – deceased 69 yo with CAD, MI
Mother – deceased 75 yo with lung cancer, heavy smoker
Brother – MI, renal failure, hyperlipidemia
No cirrhosis
No bone marrow disease
No fibrotic lung disease
IPF: Genetic Factors
Currently accounting for about 5% of the IPF population, familial
forms of IPF occur where two or more members of the same
primary biologic family are diagnosed.
TERT
TERC
telomere length
dyskeratosis congentia, anemias, liver diseases
JWM: Exam
P 69, BP 116/82, RR 33, Wt 240 lbs, 95% RA at rest, afebrile
ENT - tympanic membranes clear bilaterally; nares patent,
oropharnyx is clear with grade IV mallampati airway
Neck - no lymphadenopathy, trachea midline, no thyroid mass
Lungs - bibasilar velcro crackles, lung sounds throughout, no
wheezes
CV - RRR with no murmur, S3 or S4
GI – abd is soft, nontender, nondistended, with bowel sounds
throughout
Musculoskeletal - no cyanosis, no clubbing, no edema
Skin - no rashes or ecchymosis
Neurologic – alert and oriented x 4, CN II-XII intact, strength
intact, normal gait
JWM: Procedures
Labs
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CBC, CMP, CPK - wnl
ANA +, smooth, 1:40
RF 3
SclAb: < 0.1
Pulmonary Function
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FVC 2.75L 62%
FEV1 2.35 L 69%
FEV1/FVC ratio 85
TLC 4.14L 61%
DLCO 18.5 mL/mmHg/min 58%
6 Minute Walk Testing – walked 1050 feet with room air, no
desaturation
JWM: Dx and Initial Plan
Interstitial Lung Disease concerning for IPF by history and exam,
restrictive pattern on PFTs:
• Return for HRCT of chest and 2D echocardiogram
Referred to GERD clinic for evaluation:
• Nexium 40 mg daily
Elevated BMI:
• Weight loss efforts through exercise and diet
h/o snoring and disturbed sleep concerning for OSA:
• Refer for NPSG
Pneumovax
JWM: Return Appointment
No change on history, physical exam
Pulmonary Function:
FVC 2.68 L 61%
FEV1 2.27 L 67%
FEV1/FVC ratio 85
TLC 57%
DlCO 17.6 mL/mmHg 56%
NPSG: AHI 20.4, being set up for cpap titration
Echocardiogram:
Mild concentric LVH, with mildly dilated LA; LVEF > 55%
No evidence to support pulmonary hypertension
JWM: Return Appointment
HRCT of Chest
• Diffuse areas of peripheral septal thickening involving all lobes
of both lungs with sparing of the extreme lung apices
• Several areas of bronchiectasis of lower lobes and RML.
• Scattered areas of bronchiolectasis at the periphery
• Evidence of early honeycombing at the lung bases
• Minimal ground glass opacities seen at the bases
• No significant air trapping
• No pleural effusion
• Changes are persistent on prone imaging and expiratory
imaging.
Consistent with UIP
IPF: HRCT Features of UIP
HRCT is essential in diagnosing IPF, with the finding of honeycombing
critical for a definitive diagnosis.
Definitive UIP:
subpleural, basal predominance
reticular abnormality
honeycombing with or without traction bronchiectasis
absence of features associated with “inconsistent”
Possible UIP
Inconsistent UIP:
upper or mid-lung predominance; peribronchovascular
predominance, extensive ground glass, profuse micronodules, discrete
cysts, diffuse mosaic attenuation or air-trapping in three or more
lobes; consolidation in bronchopulmonary segments or lobes.
IPF: Histopathology Features of UIP
Key findings on biopsy include:
heterogeneous appearance at low magnification in
which areas of fibrosis with scarring and honeycomb change
alternate with area of less affected or normal parenchyma
inflammation is usually mild
subepithilial foci of proliferating fibroblasts and
myofibroblasts (the “fibroblastic foci”)
honeycomb change are usually cystic fibrotic airspaces
that are frequently lined by bronchiolar epithelium and filled
with mucus and inflammatory cells
IPF: Diagnostic Criteria
A thorough medical, occupational/environmental and family history,
physical examination, physiological testing, laboratory evaluation, and
the presence of a UIP pattern on HRCT is sufficient for diagnosis.
Diagnosis requires the following:
1. Exclusion of other known causes of ILD
2. The presence of a UIP pattern on HRCT
3. Specific combinations of HRCT and surgical lung biopsy UIP
pattern
Surgical lung biopsy is no longer essential.
Diagnostic accuracy increases with clinical, radiologic, and
histopatholgic correlation, or a multidisciplinary discussion (MDD).
JWM: Dx and Plan
Idiopathic Pulmonary Fibrosis
Treat with oral pirfenidone or nintedanib
Not a candidate (currently) for lung transplant (weight, age)
Comorbidities
Hypertension and Hyperlipidemia
• Refer to Cardiology HTN Clinic or PCP for management
Obstructive Sleep Apnea
• Schedule cpap titration
Referred to GERD clinic for evaluation
• Nexium 40 mg daily
Obesity
• Weight loss efforts through exercise and diet
IPF Treatments
FDA Approved Oral Treatments
Pirfenidone and Esbriet
Non-Pharmaceutical Treatments
Oxygen, Pulmonary Rehabilitation, Vaccines
Clinical Drug Trials
Lung Transplantation
Palliative and Hospice Care
IPF Treatments: Oral Therapy
Pirfenidone / Esbriet®
Nintedanib / Ofev ®
Reduced the proportion of patients
with a 10% decline in FVC:
35% to 17%
(a 48% change)
Reduced the mean decline in mL FVC:
240mL to 115mL
(a 48% change)
Increased stability evidenced by no
decline in FVC:
10% to 23%
(a 132% increase)
Reduced the mean decline in mL FVC:
428mL to 235mL
(a 45% change)
Increase in time to 1st Acute
Exacerbation:
9.6 % to 3.6 %
(a 37.5% change)
IPF Treatments: Oral Therapy
Pirfenidone / Esbriet®
Adverse Reactions:
nausea (36%)(2% dc’d)
other GI: abd pain, bloating,
dyspepsia, vomiting, GERD,
anorexia, weight loss
fatigue (26%)
photosensitivity (9%)
liver enzymes (3.8%)
Nintedanib / Ofev ®
Adverse Reactions:
diarrhea (62%)(4.5% dc’d)
other GI: nausea, abd pain,
bloating, dyspepsia, vomiting,
GERD, anorexia, weight loss
liver enzymes (14%)
headache (8%)
elevated bp (5%)
IPF Treatments: Oral Therapy
Pirfenidone / Esbriet®
Nintedanib / Ofev ®
Risks:
No fluoxetine
No enoxacin
Cipro 750mg BID
Hepatic Impairment?
Use with caution in Child-Pugh
Class A, B; do not use with Class C
Renal Impairment?
Use with caution
Smoking causes decreased
exposure to pirfenidone
Risks:
Arterial Thromboembolic Events
MI 1.6 %
CVA
Bleeding (nintedanib is a VEGFR
inhibitor, therefore, use with
caution with full anticoagulation
therapy)
Hepatic Impairment?
Use with caution in Child-Pugh
Class A; do not use with Class B, C
IPF Treatments: Oral Therapy
Pirfenidone / Esbriet®
Nintedanib / Ofev ®
Oral treatment 267mg
Oral treatment 150mg
3 capsules three times daily
1 capsule twice daily
with food
full dose 300 mg d
titration to full dose
full dose 2403 mg daily
Liver function monitoring:
Initiation, monthly x 6
months, then quarterly
Liver function monitoring:
Initiation, monthly x 3
months, then quarterly
IPF Treatments: Non-Pharma
Supplemental Oxygen Support
Medicare requirements support desaturation to 88% or lower
Pulmonary Rehabilitation
Medicare requirements for restrictive patterns:
FVC equal to or less than the values in a height-based
chart (70-71 inches -> 1.75 L or less)
DLCO < 10.5 mL/min/mmHg or < 40%
ABGs according to charts based on altitude and
comparing arterial PCO2 and arterial PO2.
Vaccines
influenza annually
pneumonia
PCV 13 (once)
PPSV23 (up to 3 doses q 5 years)
IPF Treatments: Clinical Trials
AF-219 vs placebo
BG0001 vs. placebo
CC-90001 (100mg vs. 200mg)
FG-3019 vs. placebo
Lebrikizumab vs. placebo
Nintedanib +/- pirfenidone
Pirfenidone + nintedanib
Riociguat vs. placebo
IPF Treatments: Lung Txplnt
Each Center in the US has specific guidelines for their programs.
Indications for Transplant Referral for IPF at Vanderbilt:
referral at the time of diagnosis
TLC < 60%
supplemental oxygen use
secondary pulmonary hypertension
clinical decline (> 10% loss of FVC in 6 months)
IPF Treatments: Lung Txplnt
Absolute Contraindications:
Active tobacco use
Active substance abuse
History of cancer within past 2 years
beliefs prohibiting blood transfusions
ventilator dependence (continuous cpap / endotrachial)
history of HIV, chronic HepC, Burkholderiea cenocepacia infections
severe comorbidities:
DM with end organ damage (nephropathy, retinopathy)
impaired renal function (GFR < 50)
severe CAD: left main, three vessel
impaired cardiac function
CTD/Autoimmune causing sign renal, GI, esophageal, or liver dz
Inadequate social support
History of medical noncompliance
IPF Treatments: Lung Txplnt
Relative Contraindications:
osteoporosis with symptomatic fractures
stented 1 or 2 vessel CAD
previous chest wall surgery
chronic narcotic use
BMI < 17; BMI > 30
cancer within 2-5 years
Age > 69, age < 14
uncontrolled infection
IPF Treatments: Palliative Care
The focus of palliative care is to reduce symptoms and provide
comfort to patients.
The primary goal is relief of suffering, both physical and
emotional.
Advanced directives and end-of-life care issues should be
addressed.
IPF Management
Natural History
10% Seemingly stable
80% Gradual decline
10 % Acute Exacerbation of IPF (acute decline after ruling
out other causes of acute respiratory worsening)
Those at increased risk of mortality at baseline presentation
include those with increased dyspnea, DLCO < 40%, desat < 88%
during 6MWT, greater extent of honeycombing on HRCT, or
pulmonary hypertension
Those at increased risk of mortality longitudinally are those who
lose > 10% FVC or > 15% in DLCO in 12 months, have increased
dyspnea and/or hypoxemia, or worsening fibrosis on HRCT.
IPF Management: Symptoms
Dyspnea
oxygen therapy
Fatigue
pulmonary rehabilitation
Cough
benzonatate
hydrocodone/chlorpheniramine syrup
IPF Management: Dz Progression
Pulmonary Function Tests
FVC
DLCO
6 Minute Walk Test
oxygen saturation on room air, or previously prescribed
oxygen liter flow
HRCT
if PFTs change significantly
IPF Management: Comorbidities
GERD
PPI, even in asymptomatic GER
Referral to GI
PAH
limited data on treatment of PAH due to IPF
sildenafil may improve quality of life
recommendation: reasonable treatment for some
OSA
cpap/bipap
CAD/HTN
referral to cardiology
JWM: Today
Current Comorbidities:
HTN/Hyperlipidemia
OSA, excellent compliance with cpap
GER
basal cell carcinoma
obesity (BMI 34.9)
Current Medications:
Started pirfenidone on 12/2014; full dose maintained
Started amlodipine, asa, and simvastatin by cardiologist
GER controlled with omeprazole daily
oxygen 4L/min/nc with exertion
JWM: Today
Pulmonary Function (01/28/2016)
FVC 1.97L 49%
DLCO 7.94 mL/min/Hg 33%
One year prior (11/06/2014):
FVC 2.12L / 52% [150mL or 7% loss]
DLCO 11.75 / 47% [32.1% loss]
6MWT
880 feet on 3L with desat to 87%
One year prior: 800 feet on 3L with desat to 94%
JWM: Today, so… What now?
- Decline in FVC by 7% in one year
- Sharp decline in DLCO by > 15% in one year
- 80 feet further in walk distance, however, reduced saturation with
the increased effort.
Treatment Plan:
Continue pirfenidone at full dose
Continue PPI, other comorbidity treatments
Continue supplemental oxygen at 4L
Consider re-evaluation of pulmonary hypertension by echo
Consider enrollment in clinical trial
Enroll in Pulmonary Rehabilitation
Weight loss
Ensure vaccines remain up to date
Not interested in Lung Transplant
Consider introduction to Palliative Care
Return in 3 months with PFTs, 6MWT
wendi.mason@vanderbilt.edu
615-343-7068