Oral Sildenafil has No Acute Effect on Diffusion Capacity Measurements in
Patients with Diffuse Parenchymal Lung Disease and Pulmonary Hypertension
Isabel Mira-Avendano
1*
, Umur Hatipoglu
1
, Catherine Sant
1
, Daniel Laskowski
1
, Ruchi Yadav
2
and Raed Dweik
1
1
Respiratory Institute, Cleveland Clinic, Cleveland, Ohio, USA
2
Imaging Institute, Cleveland Clinic, Cleveland, Ohio, USA
*
Corresponding author: Isabel Mira-Avendano, Respiratory Institute, Cleveland Clinic, Cleveland, Ohio, USA, Tel: 904-953-6728; E-mail: mira.isabel@mayo.edu
Rec date: Apr 08, 2015; Acc date: Apr 25, 2015; Pub date: Apr 27, 2015
Copyright: © 2015 Mira-Avendano I, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Diffuse parenchymal lung diseases have diverse etiology and treatment often requires individualization taking into
consideration comorbidities. Pulmonary hypertension represents one such comorbidity which, when present,
worsens prognosis and confounds approach to treatment. Sildenafil is a pulmonary vasodilator, which has recently
generated considerable interest for use in patients with diffuse parenchymal lung disease and concomitant
pulmonary hypertension.
We wondered whether acute administration of oral sildenafil affects the diffusion capacity measurement, which is
a tool for serially monitoring patients with diffuse parenchymal lung diseases.
Methods: 15 patients with diffuse parenchymal lung disease and pulmonary hypertension (WHO Class III) had
diffusion capacity measurements and 6 minute walk test performed before and after receiving sildenafil 20 mg orally.
CT scans of the chest were scored to determine burden of interstitial lung disease.
Results: The mean change in DLCO after administration of oral sildenafil was -0.26 ± 0.94 ml/min/mmHg
(p=0.30) and -0.41 ± 2.84 % predicted (p=0.58). The average 6 minute walk distance at baseline was 363.28 ± 141
meters. After oral administration of sildenafil, 6 minute walk distance was 369 ± 116 meters (p=0.63). No correlation
was observed between composite radiology scores and DLCO measurements or change in DLCO and radiology
scores (p=0.43 and p=0.17 respectively).
Conclusion: We found no acute change in diffusion capacity after a single dose of oral sildenafil in patients with
diffuse parenchymal lung disease and pulmonary hypertension.
Keywords: Pulmonary hypertension; Parenchymal lung disease;
Diffusion capacity
Introduction
Diffuse parenchymal lung diseases have diverse etiology and
treatment often requires individualization taking into consideration
comorbidities. Pulmonary hypertension represents one such
comorbidity which, when present, worsens prognosis [1,2] and
confounds approach to treatment. Furthermore, with the exception of
pulmonary hypertension in the setting of connective tissue disease-
related parenchymal lung disease, there is controversy in the utility of
treatment of pulmonary hypertension in this group of patients (WHO
Group III).
Sildenafil is a cyclic GMP selective phosphodiesterase type 5
inhibitor approved for use in patients with pulmonary arterial
hypertension. The drug has recently generated considerable interest
for use in patients with diffuse parenchymal lung disease and
concomitant pulmonary hypertension. A theoretical concern has been
the possible worsening in oxygenation when pulmonary vasodilators
are introduced to patients with abnormal ventilation perfusion
matching at baseline. In a small, but meticulously conducted
physiological studies, sildenafil has shown salutary effects with
improvement in pulmonary pressures with negligible impact on
oxygenation and ventilation perfusion mismatch [3]. In a post hoc
subgroup analysis of 84 patients with pulmonary arterial hypertension
and connective tissue disease who had been included in the SUPER-1
trial, Badesch and colleagues demonstrated improvements in exercise
capacity, hemodynamic changes and functional class, following 12
weeks of treatment with varying doses of sildenafil [4]. Later, 259
patients from the SUPER-1 trial were enrolled in an open label
extension study (SUPER-2) of 3 years duration which demonstrated
continued improvement or maintenance of functional status while on
sildenafil [5]. Recently, sildenafil was associated with small but
statistically significant improvements in diffusion capacity and
oxygenation while having no effect on 6 minute walk distance in 180
patients with advanced idiopathic pulmonary fibrosis and pulmonary
hypertension [6].
Diffusion capacity of the lung for carbon monoxide (DLCO)
measurement is ubiquitously available and is used as a tool for serially
monitoring patients with diffuse parenchymal lung diseases. The
American Thoracic Society has endorsed its use in the assessment of
patients with idiopathic interstitial pneumonias [7]. Diffusion capacity
measurements are affected by blood volume and transit time in the
capillary bed. Therefore, pulmonary vasodilators can potentially affect
measurements by altering pulmonary vascular hemodynamics.
Mira-Avendano, et al., Fam Med Med Sci Res 2015, 4:3
DOI: 10.4172/2327-4972.1000173
Research Article Open Access
Fam Med Med Sci Res
ISSN:2327-4972 FMMSR, an open access journal
Volume 4 • Issue 3 • 1000173
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