Connective Tissue Disease–associated Pulmonary
Arterial Hypertension in the Modern Treatment Era
Robin Condliffe1,2, David G. Kiely1, Andrew J. Peacock3, Paul A. Corris4,5, J. Simon R. Gibbs6, Florenc Vrapi7,
Clare Das7, Charlie A. Elliot1, Martin Johnson3, Julia DeSoyza4, Chantal Torpy6, Kim Goldsmith2,
Denise Hodgkins2, Rodney J. Hughes2, Joanna Pepke-Zaba2, and J. Gerry Coghlan7
1Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield;2Pulmonary Vascular Disease Unit, Papworth Hospital, Cambridge;
3Scottish Pulmonary Vascular Disease Unit, Western Infirmary, Glasgow;4Northern Vascular Unit, Freeman Hospital, Newcastle-upon-Tyne;
5Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne;6Department of Cardiology, Hammersmith Hospital, London; and
7Department of Cardiology, Royal Free Hospital, London, United Kingdom
Rationale: Pulmonary arterial hypertension in association with con-
nective tissue disease (CTD-PAH) has historically had a poor prog-
nosis, with a 1-year survival rate among patients with systemic
sclerosis–associated pulmonary arterial hypertension (SSc-PAH) of
45%. However, more therapies have become available.
Objectives: To investigate the survival and characteristics of all
patients diagnosed with CTD-PAH in the U.K. pulmonary hyperten-
Methods: National registry of all incident cases of CTD-PAH di-
agnosed consecutively between January 2001 and June 2006.
Measurements and Main Results: Patients with CTD-PAH (429; 73%
SSc-PAH) were diagnosed by a catheter-based approach. One- and
3-year survivalrates were78 and47% for patientswith isolatedSSc-
PAH. Survival was worse for those with respiratory disease–associ-
patients with exercise-induced SSc-PAH was superior (3-yr survival,
86%; P 5 , 0.001). Age, sex, mixed venous oxygen saturation, and
World Health Organization functional class were independent
predictors of survival in isolated SSc-PAH. Nineteen percent of
patients with exercise-induced SSc-PAH and 39% of patients with
per 1 million. The 3-year survival rate of 75% for those with
pulmonary arterial hypertension associated with systemic lupus
erythematosus (SLE-PAH) was significantly better than that for
patients with SSc-PAH (P 5 0.01).
Conclusions: Survival of patients with SSc-PAH in the modern treat-
patients with mild functional impairment or exercise-induced SSc-
PAH have evidence of disease progression. Survival of patients with
respiratory disease–associated pulmonary hypertension is inferior.
SLE-PAH has a better prognosis than SSc-PAH.
Keywords: pulmonary hypertension; connective tissue disease; sys-
temic sclerosis; systemic lupus erythematosus; survival
Connective tissue disease–associated pulmonary arterial hyper-
tension (CTD-PAH) has historically had a poor prognosis, with
a 1-year survival rate before the availability of advanced
therapies of 45% in patients with systemic sclerosis (SSc) (1).
The management of CTD-PAH in the United Kingdom has,
however, changed significantly. First, all three groups of ad-
vanced therapies—prostanoids, endothelin receptor antagonists,
and phosphodiesterase-5 inhibitors—used in idiopathic PAH
have also been shown to improve pulmonary hemodynamics
and functional status in patients with CTD-PAH (2–7). Second,
the diagnosis, prescribing, and management of all adult CTD-
PAH has been centralized to five pulmonary hypertension (PH)
centers. This has produced a unique chance to investigate the
characteristics, treatments, and survival of all patients with CTD-
PAH within a single country.
Previous studies have largely concentrated on SSc-associated
PAH (SSc-PAH), with a disease prevalence estimated to be
between 7.5 and 12% (8, 9). This has led to the introduction of
screening programs. In systemic lupus erythematosus (SLE)
estimated survival has ranged from relatively good to being
worse than in idiopathic PAH (10, 11). Even less is known about
PAH in other forms of connective tissue disease.
Using pooled data from the five PH centers in the United
Kingdom we have performed a cohort study of all incident cases
diagnosed during a 5.5-year period starting in 2001, the year
when the centers were commissioned. We hypothesized that the
prognosis in SSc-PAH has improved during the modern treat-
ment era. Using this unique national registry we also aimed to
determine incidence, prevalence, and prognostic factors in SSc-
PAH, together with outcomes in rarer forms of CTD-PAH.
Some of the results of this study have been previously reported
in the form of an abstract (12).
Details of all incident cases of CTD-PAH diagnosed consecutively at
a U.K. PH center between January 1, 2001 and June 31, 2006 were
entered into local databases at the time of diagnosis. One investigator
AT A GLANCE COMMENTARY
Scientific Knowledge on the Subject
Systemic sclerosis (SSc)–associated pulmonary arterial
hypertension (PAH) has historically had a poor outcome.
Little is known of outcomes in exercise-induced and re-
spiratory disease–associated SSc-PAH, or in PAH due to
other connective tissue diseases.
What This Study Adds to the Field
Survival of patients with SSc-PAH in the modern treatment
era is better than in historical series. Survival of patients
with respiratory disease–associated pulmonary hypertension
is inferior. SLE-PAH has a better prognosis than SSc-PAH.
(Received in original form July 24, 2008; accepted in final form October 17, 2008)
Supported by unrestricted educational grants from Actelion, LungRx, Pfizer, and
Correspondence and requests for reprints should be addressed to J. G. Coghlan,
M.D., Department of Cardiology, Royal Free Hospital, London NW3 2QG, UK.
This article has an online supplement, which is accessible from this issue’s table of
contents at www.atsjournals.org
Am J Respir Crit Care Med
Originally Published in Press as DOI: 10.1164/rccm.200806-953OC on October 17, 2008
Internet address: www.atsjournals.org
Vol 179. pp 151–157, 2009
(R.C.) subsequently visited each site to examine patient records to
confirm the diagnosis and to record clinical data. Patients given
a diagnosis of PAH at rest were excluded from the study cohort if mean
pulmonary artery pressure (Ppa) was less than 25 mm Hg, pulmonary
capillary wedge pressure was greater than 15 mm Hg, or pulmonary
induced PAH was defined as a Ppa of at least 30 mm Hg with
a pulmonary capillary wedge not more than 15 mm Hg on exercise.
was defined as development of PAH at rest at subsequent right-heart
catheterization. In patients with baseline PAH at rest, progression was
defined as both a 20% fall in walk distance and an increase in World
Health Organization (WHO, Geneva, Switzerland) functional class or,
when subsequent catheterization data were present, a 20% increase in
both Ppa and PVR.
Patients with either a forced vital capacity of less than 60%
predicted or, when no spirometry results were found, moderate or
severe fibrosis (more than one third of lung fields involved) on high-
resolution computed tomography were defined as having respiratory-
associated PH. No specific nationwide treatment algorithm was used;
advanced therapies were commenced as thought appropriate at each
center. Combination therapies were used when allowed and clinically
indicated. Patient follow-up was as per clinical need. To calculate
survival an end point of either date of death or transplant or a censor
date of January 26, 2007 was used. Date of diagnosis was taken as the
date of initial diagnostic right-heart catheterization. If this could not be
located in the hospital records then date of first visit was used.
Mortality status was ascertained from PH center records, by contacting
general practitioners, and by using the National Health Service
strategic tracing service. As this study was designed and conducted to
define current care, formal ethics approval was not required. The
national Patient Information Advisory Group was fully informed
regarding the use of patient data.
Analysis was performed with the SPSS statistical package (SPSS,
Chicago, IL). Mean and standard deviation or confidence interval
were used to describe parametric data, whereas the median and
interquartile range were used for nonparametric data. Comparison
between unpaired quantitative data was performed by independent t or
Mann-Whitney U test. Qualitative data were compared by x2test.
Factors associated with survival in isolated SSc-PAH were examined
by multiple Cox regression analysis. Additional detail on the methods
of the regression analysis is provided in the online supplement. Two
types of walk tests were in use and therefore, to combine these into
a single variable for modeling, distances were converted to a z-score
corresponding to the number of standard deviations from the mean.
Survival estimates were performed by Kaplan-Meier analyses with
comparisons performed by log-rank test. As cause of death could not
always be confidently ascribed; all-cause mortality was used in survival
statistics. A P value less than 0.05 was taken as significant throughout.
The patients included in the study cohort are shown in Figure 1.
The maximal duration of follow-up was 6 years, with a mean
follow-up of 3.3 years. Data were recorded primarily for clinical
purposes and therefore baseline demographics were not com-
plete in all cases. Right-heart catheterization details were
located in 98% of cases, gas transfer in 71% of cases, and
forced vital capacity in 79% of cases. Exercise capacity was
recorded in 82% of patients, using the 6-minute walk test in
56% and incremental shuttle walking test in 26% of cases.
Baseline pulmonary hemodynamics of patients with isolated
SSc-PAH and isolated SLE-associated pulmonary arterial hy-
pertension (SLE-PAH) were not significantly different, al-
though patients in the latter group were younger and had better
exercise tolerance and gas transfer (TLCO; Table 1).
One-, 2-, and 3-year survival for patients with isolated SSc-PAH
was 78, 58, and 47%, respectively. The survival in isolated SSc-
PAH was superior to that seen in respiratory disease–associated
PH (Figure 2). There was no significant difference in the
pulmonary hemodynamics of these two groups, although
patients in the latter group had lower gas transfer and exercise
tolerance and were more likely to be nonwhite (see Table 1).
Therapies for SSc-PAH
Sixty-two percent of patients with isolated SSc-PAH received
advanced monotherapy, 28% combination therapy, and 10% no
advanced therapy. Patients who were commenced on a single
therapy and subsequently had an additional therapy added in
were classed as having received combination therapy. Of those
receiving a single monotherapy 68% received an endothelin
receptor antagonist, 17% a prostanoid, and 15% a phosphodi-
Predictors of Mortality in Patients with Isolated SSc-PAH
Univariate analysis showed that patients under the age of 60
years had better survival as compared with patients 70 years of
age or older (Table 2). WHO functional class III or IV was
associated with more than two times the risk of death as
compared with class I or II (P 5 0.002). Patients with higher
mean right atrial pressure, Ppa, PVR, and total pulmonary
resistance had a higher risk of death. Higher cardiac index,
mixed venous oxygen saturation (SvO2), gas transfer, and walk
associated pulmonary hypertension/pulmonary arterial hypertension;
DM/PM 5 dermatomyositis/polymyositis; MCTD 5 mixed connective
tissue disease; RA 5 rheumatoid arthritis; SLE 5 systemic lupus eryth-
ematosus; SSc 5 systemic sclerosis; UCTD 5 undifferentiated connective
tissue disease; UK-PH 5 U.K. pulmonary hypertension center.
Study cohort. CTD-PH/PAH 5 connective tissue disease–
152AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL 1792009
distance were associated with a decreased risk of death.
Multiple variable analysis showed that younger age, female
sex, higher SvO2, and lower WHO functional class were in-
dependent predictors of survival. The effects on survival of anti-
nuclear, SCl-70, and anti-centromere antibody status, together
with the time from onset of connective tissue disease to
diagnosis of PAH, were also tested but were found to be
nonsignificant in both univariate and multivariate analysis.
Survival curves based on SvO2and WHO class are shown in
Figures 3A and 3B.
SSc-PAH on Exercise
Survival of the 42 patients with isolated exercise-induced SSc-
PAH compared with those with isolated SSc-PAH at rest is
shown in Figure 4. Five patients with exercise-induced SSc-
PAH subsequently died. PH and/or right-heart failure was
recorded as the main cause of death in four patients. The fifth
patient died of septicemia secondary to hepatic abscesses. Eight
patients (19%) had evidence of disease progression with sub-
sequent PAH at rest diagnosed at repeat right-heart catheter-
ization (Ppa, 35.2 6 10.2 mm Hg; pulmonary capillary wedge
pressure, 10.6 6 2.0 mm Hg; cardiac index, 2.58 6 0.49 L ? min ?
m22; PVR, 478 6 213 dyn ? s ? cm25). Mean time to PAH at rest
was 838 6 477 days from diagnosis. Seven (17%) patients
required advanced therapies within 3 years of diagnosis.
SSc-PAH with Good Functional Class
Although survival of patients with isolated SSc-PAH at rest who
were in functional class I and II at baseline was superior to that
of patients in classes III or IV, mortality was still appreciable
(see Figure 3B). Three of the 41 patients refused clinical follow-
up. Evidence of disease progression was found in 15 (39%) of
the remaining patients during follow-up, and in 7 (88%, all of
whom received advanced therapy) of the 8 patients who died
and had follow-up. Disease progression was confirmed by
hemodynamics in eight patients and by a combination of both
a 20% fall in walk distance and an increase in WHO class in
seven patients who had not undergone repeat right-heart
catheterization. Mean time to clinical worsening was 840 6
414 days from diagnosis.
Incidence and Prevalence Estimates
Assuming a U.K. population of 60 million, the incidence of
CTD-PAH at rest, diagnosed within the U.K. PH Service,
increased from 0.68 per million per year in 2001 to 1.55 per
million per year in 2005. The population prevalence, on June 31,
2006, of patients diagnosed within the U.K. PH service was 4.23
per million for CTD-PAH at rest and 2.93 per million for SSc-
PAH at rest.
Other Disease Types
One- and 3-year survival rates for isolated PAH associated with
SLE were 78 and 74%, with polymyositis/dermatomyositis (PM/
DM) they were 100 and 100%, with MCTD they were 89 and
63%, and with rheumatoid arthritis they were 83 and 66%,
respectively. When compared with SSc-PAH, only the survival
of SLE-PAH (P 5 0.01; Figure 5) and PM/DM-PAH (P 5 0.03)
were significantly better. Of patients with SLE 75% were
treated with advanced therapy whereas 86% received immuno-
suppression; 11% had an immunosuppressive started and 75%
were already immunosuppressed. In contrast to patients with
isolated PAH, the superior survival seen in patients with other
forms of CTD when compared with SSc did not extend to those
patients with respiratory disease–associated PH.
This article reports the findings of the largest ever study of
connective tissue disease–associated pulmonary hypertension
involving patients with a right-heart catheter-based diagnosis. It
incorporates the vast majority of such patients within a single
nation and, importantly, includes only incident cases. We have
therefore been able to define the medium to long-term outcome
in patients with both SSc-PAH and other less well studied forms
of CTD-PAH. In an unselected cohort of patients with SSc-
PAH we have demonstrated improved survival when compared
with early historical data, where median survival was found to
be less than 2 years (1, 13).
Although some later studies have demonstrated superior
survival they have involved prevalent and selected patients
TABLE 1. BASELINE DEMOGRAPHICS
(n 5 259)
(n 5 56)P Value*(n 5 28)P Value†
Ppa, mm Hg‡
PVR, dyn ? s ? cm25‡
WHO I and II/III/IV, %
63.9 (10.5) 57.9 (11.4) ,0.001 42.0 (12.9) ,0.001
2.43 (0.73) 2.38 (0.72)
41.5 (14.8) 29.1 (10.1) ,0.001 59.2 (12.1) ,0.001
231 (216) 146 (124)0.03
Definition of abbreviations: 6MWT 5 6-minute walk test; CI 5 cardiac index;
Ppa 5 mean pulmonary artery pressure; SvO25 mixed venous oxygen saturation;
PVR 5 pulmonary vascular resistance; SLE-PAH 5 systemic lupus erythematosus–
associated pulmonary arterial hypertension; SSc-PH/PAH 5 systemic sclerosis–
associated pulmonary hypertension/pulmonary arterial hypertension; TLCO 5
percentage predicted gas transfer; WHO I, II, III, and IV 5 World Health
Organization functional classes.
Values represent mean (standard deviation) or percentage unless otherwise
* Isolated SSc-PAH versus respiratory-associated SSc-PH.
†Isolated SSc-PAH versus isolated SLE-PAH.
‡Median (interquartile range).
and isolated or respiratory disease–associated pulmonary hypertension.
Survival from diagnosis of patients with systemic sclerosis
Condliffe, Kiely, Peacock, et al.: U.K. CTD-PAH Registry153
(4, 13, 14). Our survival rates concur with those seen previously
in a smaller cohort of unselected incident cases (15). It is
impossible to exclude the contribution of lead-time bias toward
the improved survival we have demonstrated. However, even if
the observed improvement is real the prognosis in SSc-PAH
remains relatively poor, highlighting the need for more effective
Survival of patients with respiratory-associated SSc-PH was
significantly worse than that of patients with isolated SSc-PAH.
Chang and colleagues previously found no significant difference
in survival between 119 SSc patients with isolated PH and 112
SSc patients with a combination of restrictive lung disease and
PH (16). A limitation of that study, however, was that no right-
heart catheterization data were presented, with PH defined as
an echocardiographically estimated systolic pulmonary artery
pressure of less than 35 mm Hg. Patients with PH in association
with hypoxic lung disease often have relatively mildly elevated
pulmonary pressures with preserved or increased cardiac output
(17). It is interesting to note that in the present study cohort,
patients with both SSc and significant respiratory disease had
disturbances in pulmonary hemodynamics that were dispropor-
tionate to the underlying lung disease and were more akin to
TABLE 2. PREDICTORS OF MORTALITY IN ISOLATED SYSTEMIC SCLEROSIS–ASSOCIATED PULMONARY
Univariate Analysis Multiple Analysis
n Univariate HR‡
P Value Multiple HR‡
Pra, per 5 mm Hg
25–33 mm Hg
34–42 mm Hg
43–50 mm Hg
51–74 mm Hg
CI, per 0.5 L/min/m2
PVR, per 100 dyn ? s ? cm25
277–560.0 dyn ? s ? cm25
561–865 dyn ? s ? cm25
866–1,233 dyn ? s ? cm25
1,234–3,032 dyn ? s ? cm25
21.70 to 20.78
20.79 to 20.007
20.008 to 0.70
0.71 to 3.41
Year of diagnosis
0.61 (0.32, 1.16)
0.58 (0.34, 0.96)
1.14 (0.76, 1.74)
0.02 0.66 (0.34, 1.29)
0.40 (0.22, 0.71)
0.81 (0.52, 1.27)
1.39 (0.89, 2.15)
2.20 (1.36, 3.55)
2.70 (1.45, 5.01)
1.43 (1.22, 1.69)
2.26 (1.02, 4.97)
1.23 (0.69, 2.20)
2.77 (1.65, 4.67)
2.30 (1.34, 3.97)
0.77 (0.67, 0.89)
1.10 (1.06, 1.14)
2.55 (1.40, 4.65)
2.51 (1.37, 4.61)
4.69 (2.64, 8.34)
0.40 (0.24, 0.66)
0.40 (0.25, 0.66)
0.16 (0.09, 0.31)
0.36 (0.22, 0.59)
0.38 (0.23, 0.63)
0.17 (0.09, 0.33)
0.56 (0.34, 0.91)
0.35 (0.20, 0.60)
0.21 (0.11, 0.39)
0.63 (0.37, 1.05)
0.83 (0.50, 1.37)
0.46 (0.26, 0.83)
0.42 (0.22, 0.78)
1.39 (0.86, 2.26)
0.83 (0.49, 1.38)
0.72 (0.43, 1.22)
0.62 (0.34, 1.11)
1.52 (0.86, 2.69)
0.96 (0.64, 1.43)197 0.83
Definition of abbreviations: HR 5 hazard ratio; Pra5 mean right atrial pressure; TPR, total pulmonary resistance.
* n 5 259.
†Variables grouped where appropriate into quartiles.
‡Hazard ratios are presented with 95% confidence intervals.
xMore than 10% of patients with missing data.
154AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINEVOL 1792009
those seen in isolated SSc-PAH. Only three patients with
respiratory-associated SSc-PH underwent transplantation dur-
ing the study period. It is likely that this reflects the increased
risk of transplantation in this group of patients related to factors
such as gastroesophageal reflux disease and renal disease.
However, the poorer outcome with standard therapy in this
group of patients especially suggests that prompt referral for
transplant assessment of suitable patients should be considered.
Age, sex, mixed venous oxygen saturation, and WHO func-
tional class were identified as independent prognostic factors
and may be useful in decision-making regarding advanced ther-
apies. Several hemodynamic variables that correlated with each
other were included for consideration in the multiple regression
model. Parameters, such as PVR, which were significant in
univariate but not multivariable analysis are therefore still of
Although patients with exercise-induced SSc-PAH clearly had
a better prognosis than patients with SSc-PAH at rest, mortality
was not negligible, with the majority of these deaths being
attributed to PH. Furthermore, evidence of disease progression
to PAH at rest was found in almost one fifth of patients with SSc
and exercise-induced PAH, and in 60% of those patients who
died. It would therefore appear prudent to monitor patients with
exercise-induced PAH to ensure that any deterioration in
pulmonary hemodynamics is recognized early, allowing timely
commencement of advanced therapy. Mortality of patients with
isolated SSc-PAH at rest who were in WHO classes I and II was
appreciable. Furthermore, more than one third of patients had
evidence of disease progression during follow-up. The results of
a randomized controlled trial into the effects of bosentan on
patients in WHO functional class II (18% of whom had CTD-
PAH) have been published (18). Both PVR and time to clinical
worsening were improved in the treatment arm. Given the
observed mortality in our study, patients with SSc-PAH in
WHO class II may be a suitable group in which to study the
effect of treatment on survival.
grouped by (A) median mixed venous oxygen saturation and (B) World
Health Organization (WHO) functional class.
Survival from diagnosis of patients with isolated systemic
pulmonary arterial hypertension(SSc-PAH)
sclerosis–associated pulmonary arterial hypertension at rest or on
Survival from diagnosis of patients with isolated systemic
sclerosis–associated pulmonary arterial hypertension and systemic
lupus erythematosus–pulmonary arterial hypertension.
Survival from diagnosis of patients with isolated systemic
Condliffe, Kiely, Peacock, et al.: U.K. CTD-PAH Registry155
Two national studies estimated the prevalence of CTD-PAH
to be 2.3 and 10 cases per million within the general population
(19, 20). Our estimates of 4.23 per million for CTD-PAH and
2.93 per million for SSc-PAH are in rough agreement with these
There is a relative paucity of literature regarding the outcome
of CTD-PAH in conditions other than SSc. Chung and colleagues
retrospectively studied 20 patients with SLE-PAH, 55% of whom
received advanced therapy and 45% of whom received immu-
nosuppression (11). They found a median survival of 13 months.
Even less is known regarding the outcome of patients with other
forms of CTD-PAH. We have demonstrated that isolated SLE-
PAH in the modern treatment era has a relatively good prognosis
compared with SSc-PAH, although there was a group of patients
with rapidly progressive SLE-PAH who died within 1 year of
diagnosis. Sanchez and colleagues found that about 40% of
patients with SLE-PAH responded to immunosuppression (21).
We were unable to study the effect of immunosuppression on
survival as the number of untreated patients was small. There
were too few numbers with other CTD types to make many
definite conclusions, although the good prognosis in patients with
isolated PM/DM-PAH is noted.
The main limitations of this study are its observational,
uncontrolled nature and the fact that much of the data was
collected retrospectively, meaning that gaps in the data were
unavoidable. As such, only inferences rather than firm con-
clusions can be made regarding possible effects of treatment.
However, data regarding survival are robust and will not have
been affected by the study design. Our estimates of prevalence
did not include cases that were prevalent at the beginning of our
inclusion period. However, because of the length of our study
and the poor prognosis in CTD-PAH, the point prevalences at
the end of our inclusion period are probably representative of
the true prevalence of diagnosed and treated disease. These
figures are likely to be conservative estimates of the true
prevalences as they include only patients who had been di-
agnosed at a PH center. Few patients, however, will have been
diagnosed and treated appropriately elsewhere because funding
bodies in the United Kingdom will fund advanced therapies
only if prescribed by one of the national PH centers. The
comparison of survival between disease types is hampered by
confounding variables such as differing ages of the specific
disease populations. However, in the clinical setting it is useful
to be able to compare the likely outcome of a typical patient
with a rarer form of CTD-PAH with that of a typical patient
with the more commonly seen SSc-PAH.
In conclusion, although survival in SSc-PAH may have
improved when compared with historical data from before the
modern treatment era it remains unacceptably poor. Further
research into the use of advanced therapies specifically in CTD-
PAH is needed. Patients with respiratory disease–associated PH
have a poorer outcome. The clinical course of patients with both
exercise-induced SSc-PAH and with SSc-PAH at rest who are
in WHO functional classes I and II, although being superior to
that of patients with PAH at rest in classes III and IV, reinforces
the importance of monitoring these groups of patients for
evidence of disease progression. Finally, we have demonstrated
that the prognosis with current therapeutic regimens is signif-
icantly better in some of the other groups of CTD-PAH,
Conflict of Interest Statement: R.C. has received support for attending confer-
ences for Encysive, Actelion, and United Therapeutics. He has also received
honoraria from Actelion. D.G.K. has received consultancy and lecturing fees and
been funded to attend conferences for Actelion, GlaxoSmithKline, Pfizer,
Encysive, and Schering Pharmaceuticals. A.J.P. has received fees for consultan-
cies, lectures, and advisory board attendance from GlaxoSmithKline, Pfizer,
Actelion, and Encysive totaling less than $20,000 pa. P.A.C. has received lecture
and advisory board fees from Pfizer, GlaxoSmithKline, Actelion, and Encysive. He
has also received an unrestricted research grant to support a clinical fellow from
Encysive to the sum of £60,000. J.S.R.G. does not have a financial relationship
with a commercial entity that has an interest in the subject of this manuscript.
F.V. does not have a financial relationship with a commercial entity that has an
interest in the subject of this manuscript. C.D. does not have a financial
relationship with a commercial entity that has an interest in the subject of this
manuscript. C.A.E. has received lecture fees during 2005–2008 totaling less than
$3,000 from pharmaceutical companies (Actelion and Encysive) and has been
sponsored to attend scientific meetings during the same time period (Actelion,
Encysive, and Schering). M.J. has received lecture fees from Actelion, Encysive,
and GlaxoSmithKline. J.D. does not have a financial relationship with a commer-
cial entity that has an interest in the subject of this manuscript. C.T. does not
have a financial relationship with a commercial entity that has an interest in the
subject of this manuscript. K.G. does not have a financial relationship with
a commercial entity that has an interest in the subject of this manuscript. D.H.
does not have a financial relationship with a commercial entity that has an
interest in the subject of this manuscript. R.J.H. has received consultancy fees
from Encysive and has received sponsorship from Encysive and Actelion for
meeting attendance. He has also received fees for lecturing from Actelion. J.P.-Z.
has received fees for lecturing and consultancies and for sitting on advisory
boards from Schering, Pfizer, Actelion, and Encysive Pharmaceuticals. She also
received £75,000 from Lung Rx, Pfizer, Actelion, and Schering to fund the post
leading to this data collection and analysis. J.G.C. provides consultancy services
for Actelion and Encysive, as well as speaking at conferences and meetings
sponsored by them. He has received £15,750 over 3 years for these activities.
In addition, two nurses in the unit are funded by Actelion and Encysive,
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