Dr.

Daniel Miller
is a ffth year
Resident in the
Respiratory
Medicine training
program at the
University of Calgary in Calgary,
Alberta. He completed his Internal
Medicine and Medical School
training at the University of
Alberta in Edmonton.
Past newsletters:
Idiopathic Pulmonary Fibrosis:
optimizing the diagnosis and
multi-disciplinary decision-
making by Dr. Gerard Cox
IPF: understanding the natural
history and epidemiology of this
fatal disease by Dr. Charlene D.
Fell
How recent randomized controlled
trials inform clinical treatment of
IPF: the therapeutic trials roller
coaster ride by Dr. Charles K.N.
Chan
Genetics in idiopathic pulmonary
fbrosis: impact on outcome and
patient management by Dr. Jolene
Fisher
Protein-based biomarkers in
IPF: current evidence and future
directions by Dr. Deborah Assayag
Upcoming newsletters:
The next several newsletters
will be based on presentations
from the ATS 2014 International
Conference and the US PFF
Summit 2013: From Bench to
Bedside.
If you wish to receive the
newsletters by email, wish to
subscribe or unsubscribe, or have
any questions, please contact:
Anna Liachenko, MSc
514-435-7860
anna@z-zinc.com
Talking with IPF Patients: Truth-Telling While
Maintaining Hope
by Daniel Miller, BSc (Engg), MD
Effective communication is a core competency of any healthcare professional. In the United States, the
Accreditation Council for Graduate Medical Education lists Interpersonal and Communication Skills as a
core competency. These skills are defned as communication skills that result in the effective exchange
of information and collaboration with patients
1
In Canada, the Royal College of Physicians and Surgeons
has identifed seven different domains that a competent physician is evaluated in, one of which is the role
of Communicator. This role is considered so important as it is essential for establishing rapport and trust,
formulating a diagnosis, delivering information, striving for mutual understanding, and facilitating a shared plan
of care.
2
One may argue that the Physicians ability to deliver appropriate information and establish mutual
understanding is even more important in the current era where any patient able to access the Internet is privy
to a limitless supply of information. Effective communication is especially important in the care of patients with
interstitial lung disease (ILD) as they suffer from a complex disease that is diffcult to diagnose and may have a
poor prognosis. This article is based on a lecture given by Dr. Jeff Swigris, of the National Jewish Health Center
in Denver Colorado, at the 2013 Pulmonary Fibrosis Foundation Summit.
Tis is a newsletter series in the continuing educational program
designed to bring you articles by leading respirologists who are experts
in fbrosing diseases.
Educating a patient about the diagnostic process
Te frst communication-related task for the Physician who treats patients with ILD is to educate the patient
about the process of reaching a specifc diagnosis. At the frst appointment, the patient should be counseled
that the diagnostic process may require a few meetings. Te American Toracic Society (ATS) Guidelines for
the Diagnosis and Management of Idiopathic Pulmonary Fibrosis (IPF) specify that the diagnosis requires both
the exclusion of other causes of ILD and appropriate imaging and/or pathology.
3
As stated in these guidelines,
the frst criteria (excluding other causes of ILD) is broad and inherently subjective and the patient needs to
understand that satisfying these criteria may be aided by observing the evolution of clinical data over time.
Educating the patient about the diagnostic process early on in the therapeutic relationship should prevent some
frustration on the patients part and aid the development of rapport and trust with the Physician. For more
information on investigations that may be appropriate for the diagnosis of ILD, the reader is referred to the ATS
Guidelines cited above.
3
Explaining disease prognosis to a patient
Te second communication-related task for the Physician who treats patients with ILD is to educate the
patient about the prognosis associated with his or her disease. Many patients will have accessed other sources
of information regarding their disease prior to meeting with an ILD Physician and most of this information is
quite dire. Part of the issue is that most of this information will be specifcally about patients with IPF, which
may or may not apply to the patient being investigated for an ILD. A commonly quoted number for the median
survival of patients with IPF is approximately three years.
4
While there is some evidence supporting this number
the individual patient must be counseled on the applicability of statistics derived from studying a subset of a
population to an individual person. Additionally, it needs to be stressed to the patient who is being investigated
for an ILD that they may or may not end up being diagnosed with IPF. Nicholson and colleagues demonstrated
quite nicely that the prognosis of diferent ILDs varies considerably (see Figure 1).
4
Teir results do suggest that
the median survival of patients with a diagnosis of usual interstitial pneumonia (UIP) is approximately three
years, but that other histopathologic subtypes of ILD have an improved prognosis.
If the patient should have their ILD diagnosed as IPF it is imperative that the Physician communicate
efectively and clearly about the evidence available regarding their prognosis. As noted above in a commonly
quoted statistic, the patient will likely discover on their own when they access the Internet that the median
survival is approximately three years. Te Physician should educate the patient about the inherent difculties
Learning objectives:
1. Recognize physician's core competency as communicator
2. Understand the basics of disclosing the diagnosis of interstitial
lung disease (ILD) to the patient
3. Examine how to best counsel the patient about the ILD
prognosis and survival
Sponsored by an unrestricted educational grant from InterMune.
The Honeycomb Network
THE IPF EXPERT EXCHANGE
Brown and colleagues have also investigated the efect of diferent
clinical variables on survival in IPF.
6
Tey corroborated some of the
results presented in the review by Ley et al by showing that the following
had a positive efect on prognosis: higher BMI, higher FVC, and higher
DLCO. Te unique part of their work was that they identifed a cohort
of patients with IPF who survived longer than 5 years from their date
of diagnosis. Tey showed that these individuals were not living on
borrowed time, but actually continued to have improved survival over
time. Teir results indicated that those patients who survive with IPF
actually continue to have an improved survival over time (see Figure 2).
Tese data can be a very powerful tool when counseling a patient with
IPF about the prognosis of their disease.
To aid efective communication, the Physician who manages patients
with ILD should also be knowledgeable about the techniques available
to efectively break bad news to their patients. Tere is a large amount
of literature available on this topic and numerous protocols exist for
structuring a conversation with a patient and their family regarding a
life-limiting disease.
7
Tese diferent protocols generally incorporate
the same steps in preparing for and carrying out these discussions
(see Table 1).
Te Royal Colleges description of the Communicator role specifes
that it assists the Physician in delivering information. Providing the
patient with resources that carry reliable information about their disease
is also an efective communication tool. Additionally, many of these
sites also contain support groups that can be of immense beneft to the
patient struggling with their diagnosis. Some useful sites for patients
with ILD are as follows:
www.pfresearch.org
www.pfdoc.org
www.pulmonaryfbrosis.org
www.canadianpulmonaryfbrosis.ca
REFERENCES:
1. http://www.acgme.org/acgmeweb/Portals/0/PFAssets/ProgramRequirements/
CPRs2013.pdf
2. http://www.royalcollege.ca/portal/page/portal/rc/canmeds/framework
3. Raghu et al. An Offcial ATS/ERS/JRS/ALAT Statement: Idiopathic Pulmonary Fibrosis:
Evidence-based Guidelines for Diagnosis and Management. Am J Respir Crit Care Med
2011; 183:788-824.
4. Nicholson et al. The Prognostic Signifcance of the Histologic Pattern of Interstitial
Pneumonia in Patients Presenting with the Clinical Entity of Cryptogenic Fibrosing
Alveolitis. Am J Respir Crit Care Med 2000;162:2213-17.
5. Ley et al. Clinical Course and Prediction of Survival in Idiopathic Pulmonary Fibrosis.
Am J Respir Crit Care Med 2011;183:431-40.
6. Brown et al. Dynamic Patient Counseling - A Novel Concept in Idiopathic Pulmonary
Fibrosis. Chest 2012;142:1005-10.
7. Harrison and Walling. What Do We Know About Giving Bad News? A Review. Clinical
Pediatrics 2010;49:619-26.
8. Arnold and Egan. Breaking the Bad News to Patients and Families: Preparing to
Have the Conversation About End-of-Life and Hospice Care. Am J Ger Cardiol
2004;13:307-12.
in applying statistics derived from studying a population to the natural
progression of disease in an individual patient. Te patient will often
perseverate greatly on these numbers, and if they live longer than the
median survival they may feel like theyre living on borrowed time.
Tese statistics can be misleading as there is heterogeneity in the clinical
course of patients diagnosed with IPF.
How disease survival statistics in IPF apply to
individual patients
Ley and colleagues published a review on prediction of survival in IPF
and summarized the clinical predictors that have been identifed.
5
Tis
review highlighted a number of clinical, radiographic, and physiologic
variables that have some evidence for diferentiating prognosis in
IPF patients. Some of the clinical predictors associated with a poorer
prognosis were: older age, male sex, worse dyspnea scores, presence
of digital clubbing, lower body mass index (BMI), and presence of
pulmonary hypertension. Radiographically the overall extent of fbrosis
correlates inversely with survival. Physiologic variables that have been
shown to correlate with survival include the forced vital capacity (FVC)
and difusing capacity of the lungs for carbon monoxide (DLCO), and
more specifcally the decline in these variables over a 6-to-12 month
interval. Six-minute walk distance, desaturation during this test, and a
decline in the distance walked over a 6 month time period have also been
shown to identify those IPF patients with a poorer prognosis. Using these
variables to diferentiate patients with a better or worse prognosis can be a
powerful tool for the Physician counseling a patient about their diagnosis.
FIGURE 2. Idiopathic pulmonary fbrosis survival contingent on annual survival.
6
%

s
u
r
v
i
v
a
l
Months
0 12 24 36 48 60 72 84 96 108 120
--- 5 year surviors
--- 4 year surviors
--- 3 year surviors
--- 2 year surviors
--- 1 year surviors
--- All-comers
0
25
50
75
100
FIGURE 1. Survival of usual interstitial pneumonia (UIP), fbrotic nonspecifc
interstitial pneumonia (NSIP), and desquamative interstitial pneumonia (DIP)/
respiratory bronchiolitisassociated interstitial lung disease (RBILD)/cellular
NSIP subgroups of interstitial pneumonia in patients originally classifed as having
cryptogenic fbrosing alveolitis (CFA).
4
Months
100
75
50
25
0
0 20 40 60 80 100
Fibrotic NSIP
DIP/RBILD/Cellular NSIP
UIP
%

s
u
r
v
i
v
a
l
N Engl J Med 2007;356:1317-26.
TABLE 1. Breaking Bad News Protocol
1. Create a conducive environment (a private space,
limited interruptions).
2. Find out what a patients current understanding
is regarding their disease.
3. Discover how much information the patient wants at this meeting
(more may be shared in future meetings).
4. Share the information slowly and clearly (avoid medical terms,
invite feedback, wait for questions).
5. Respond to the patients and family members experience
(validate their feelings).
6. Plan for additional meetings and future therapeutic interventions
(can transition into information on palliative care).
Dr. Tifany Winstone
is a fourth year resident
in the Respiratory
Medicine program
at the University of
British Columbia.
She completed her medical degree
and Internal Medicine residency in
Vancouver. She has a particular interest
in interstitial lung disease and plans to
pursue additional training in this feld.
on adjusted analysis. Tese fndings difer from idiopathic pulmonary
fbrosis (IPF) where radiological and histopathological features of usual
interstitial pneumonia (UIP) are strong predictors of poor outcome.
Additional research is required to determine the independent prognostic
importance of radiological pattern.
Methods
Tree databases were searched to identify all studies relating to
predictors of mortality or ILD progression in SSc-ILD. Te initial search
identifed 3145 unique citations.
Study Selection
Studies were eligible if they were:
published in English
evaluated potential predictors of survival and/or ILD progression
in 10 or more adults with SSc-ILD.
ILD progression was defned by worsening forced vital capacity
or radiological fndings of fbrosis. Tere was no restriction on study
design, study quality, or duration of follow-up.
Data Analysis
Twenty-seven studies met inclusion criteria, including 6 abstracts (see
Table 1). A total of 1616 patients with SSc-ILD were included. Study
quality was assessed using the Critical Appraisal Skills Program. We
report hazard and/or odds ratios for predictors of mortality and ILD
progression in SSc-ILD. Results are grouped according to pre-defned
categories including patient-specifc variables, ILD-specifc variables,
and SSc-specifc variables.
Te main limitation of this systematic review is that included studies
were of variable methodological quality. Most predictors were identifed
in only one study and there were few studies with rigorous multivariate
analyses. Despite these limitations, the data provide a framework for
future research and suggest several areas for future investigation.
Results and Discussion
Te fndings are shown in Figure 1 and Tables 2 and 3. Difusing
capacity of the lungs for carbon monoxide (DLCO) was identifed in
multiple studies as a signifcant predictor of mortality in both unadjusted
and adjusted analyses. Te strong association of DLCO with mortality is
likely related to DLCO being a marker for the severity of both ILD and
pulmonary hypertension.
Forced vital capacity (FVC) was an unadjusted predictor of mortality
in multiple studies, but was not identifed as an independent predictor in
any of the multivariate analyses. Further research is required to validate
FVC as an outcome measure in SSc-ILD.
Several radiological variables predicted prognosis on unadjusted
analysis, however extent of disease on high-resolution computed
tomography (HRCT) was the only radiological predictor of mortality
Predictors of Mortality and Progression in Scleroderma-
Associated Interstitial Lung Disease: A Systematic Review
Learning objective:
1. To conduct a systematic review to identify variables that predict mortality
and ILD progression in SSc-ILD
Interstitial lung disease (ILD) is the leading cause of morbidity and mortality in patients with systemic
sclerosis (SSc), however prognostication of SSc-ILD remains challenging. We conducted a systematic
review to identify variables that predict mortality and ILD progression in SSc-ILD. The results
available in this article were frst presented at the US Pulmonary Fibrosis Foundation Summit 2013:
From Bench to Bedside and subsequently published in Chest 2014 Feb 27. doi:10.1378/chest.13-2626.
TA Winstone
1
, D Assayag
2
, PG Wilcox
1
, JV Dunne
1
, CJ Hague
3
, J Leipsic
3
, HR Collard
2
, CJ Ryerson
1
1. Department of Medicine, University of British Columbia, Canada.
2. Department of Medicine, University of California San Francisco, CA
3. Department of Radiology, University of British Columbia, Canada
* Published in abstract form only. N/R - not reported.
TABLE 1. Study selection (n=27)
Study Enrollment n
Al-Dhaher 2010
Beretta 2007
Boin 2010*
Bouros 2002
De Lauretis 2010*
De Santis 2010
De Santis 2011
Fertig 2009
Fischer 2008
Goh 2007
Goh 2008
Goh 2011
Khanna 2011
Kim 2001
Kuwana 2012*
Launay 2006
Launay 2011
Le Gouellec 2012*
Lopes 2011
Roth 2011
Shahane 2010*
Steen 1994
Strange 2008
Swigris 2009
Trad 2006
Volpinari 2011
Zhang 2012*
1994-2004
N/R
N/R
1985-1997
N/R
2003-2005
2007-2009
1982-2005
1983-2005
1990-1999
1990-1999
1990-1999
2000-2004
1990-1999
1980-1995
1991-2001
2001-2006
N/R
2002-2005
2000-2004
N/R
1972-1989
2000-2004
1983-2005
1980-2004
N/R
N/R
27
18
22
74
74
73
46
97
22
141
215
168
77
40
50
50
47
75
35
112
133
116
141
83
52
79
N/R
models for SSc-ILD. Such studies would likely require a coordinated
multicenter efort given the relative rarity of SSc-ILD and the need for a
large and distinct cohort for appropriate validation.
Conclusions
Mortality and ILD progression in SSc-ILD were predicted by several
patient-specifc, ILD-specifc and SSc-specifc factors. Additional
prospective studies are required to validate these preliminary fndings
and identify combinations of variables that accurately predict prognosis
of SSc-ILD.
An accurate clinical prediction model could have a signifcant
impact on patient care in SSc-ILD by identifying high-risk individuals.
Additional studies are required to derive and validate clinical prediction
p value
TABLE 2. Statistically signifcant predictors of mortality
on unadjusted analysis in multiple studies
Variable Study Hazard Ratio
Le Gouellec 2012*
Bouros 2002
Goh 2008
Steen 1994
Le Gouellec 2012*
Bouros 2002
Goh 2008
Launay 2011
Trad 2006
De Santis 2010
Goh 2008
De Santis 2010
Goh 2008
N/R
N/R
0.99
N/R
N/R
N/R
0.95
0.96
N/R
N/R
1.03
N/R
4.78
<0.05
0.007
<0.01
<0.01
<0.05
0.004
<0.0005
0.01
0.007
0.035
<0.0005
0.048
<0.0005
FVC
DLCO
HRCT Fibrosis Severity
PAH/PH
* Published in abstract form only. FVC - forced vital capacity; DLCO - diffusing
capacity of the lungs for carbon monoxide; HRCT - high-resolution computed
tomography; PAH/PH - pulmonary arterial hypertension/pulmonary hypertension;
N/R - not reported.
Predictors of mortality in systemic sclerosis with interstitial lung disease (p<0.05)
Patient-specifc variables
Physiological variables Radiological variables Bronchoscopic variables Laboratory/Other variables
ILD-specifc variables SSc-specifc variables
Age
Male gender
DLCO
DLCO at 3 yrs
End-stage lung disease
FEV1
FVC
FVC/DLCO
SpO
2
Alveolar score
Extent of disease
Presence of honeycombing
Proportion of ground glass
Reticulation
Eosinophils >2%
Neutrophils >4%
Anticentromere antibody
dSSc
LEVF
PAH/PH
Pericardial effusion
C-reactive protein
Elevated KL-6
Hemoglobin level
Rapid DTPA pulmonary clearance
FIGURE 1. DLCO - diffusing capacity of the lungs for carbon monoxide; FEV
1
- forced expiratory volume in 1 second; FVC - forced vital capacity; SpO
2
- peripheral
capillary oxygen saturation; dSSc - diffuse systemic sclerosis; LVEF - left ventricular ejection fraction; PAH/PH - pulmonary arterial hypertension/pulmonary hypertension;
KL-6 (serum biomarker for interstitial lung disease); DTPA - diethylenetriamine penta-acetic acid.
REPORT on IPF from the American Thoracic Society
2014 International Conference
On Sunday 18
th
May 2014, results from three randomized controlled trials in IPF (ASCEND, INPULSIS and PANTHER) were presented during
the New England Journal of Medicine and Te Journal of the American Medical Association (NEJM/JAMA) session at the American Toracic Society
Congress in San Diego. Te session was attended by more than 1000 people and chaired by the chief editors of JAMA and NEJM. It was unanimously
recognised that this ATS session was an important time for IPF research and for patients fghting this devastating disease. Te trials will be presented
in the July (ASCEND and INPULSIS) and August (PANTHER) editions of the IPF Expert Exchange newsletter.
Summary of trials
ASCEND data were presented by Dr. Talmadge King. Pirfenidone met the primary endpoint of change from baseline to week 52 in % predicted
FVC, p<0.001. Te results of the secondary endpoints showed a signifcant diference in the change in the 6-min walk distance and in progression-free
survival. In the pooled analysis (ASCEND and CAPACITY), pirfenidone signifcantly reduced the risk of death at 1 year by 48% and the risk of death
from IPF by 68%. Pirfenidone was considered as generally safe. INPULSIS data were presented by Dr. Luca Richeldi. Nintedanib met the primary
endpoint in both studies but there was no consistency for the secondary endpoints (acute exacerbations and St. George's Respiratory Questionnaire)
between the two studies. Tere was no diference in death between nintedanib and placebo. Te main side-efects associated with nintedanib were
diarrhea (62-63%), nausea (22-26%), vomiting (13-10%) and weight loss (8-11%). PANTHER results were presented by Dr. Ganesh Raghu. Te
primary and secondary endpoints were not met. In addition, there were no diferences between N-acetyl cysteine and placebo in the rate of death.
p value
TABLE 3. Statistically signifcant predictors of mortality
on multivariate analysis in multiple studies
Variable Study Hazard Ratio
Bouros 2002
Goh 2007
Goh 2008
Launay 2011
Goh 2007
Goh 2008
Trad 2006
N/R
0.97
N/R
3.96
2.73
N/R
5.07
0.04
0.004
<0.0005
0.004
0.009
<0.0005
0.038
DLCO
PAH/PH
DLCO - diffusing capacity of the lungs for carbon monoxide; PAH/PH - pulmonary
arterial hypertension/pulmonary hypertension; N/R - not reported.