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ABSTRACT: ABSTRACT BACKGROUND: Idiopathic pulmonary fibrosis is a progressive lung disease with pulmonary vasculopathy. OBJECTIVE: To determine whether sildenafil improves six minute walk distance (6MWD) in subjects with right ventricular dysfunction. MEASUREMENTS: The IPFnet conducted a randomized trial examining the effect of sildenafil on 6MWD in patients with advanced IPF, defined by DLCO <35% predicted. A substudy examined 119/180 randomized subjects where echocardiograms were available for independent review by two cardiologists. Right ventricular (RV) hypertrophy (RVH), right ventricular systolic dysfunction (RVSD) and right ventricular systolic pressure (RVSP) were assessed. Multivariable linear regression models estimated the relationship between RV abnormality, sildenafil treatment and changes in 6MWD, St. George's Respiratory Score (SGRQ), EuroQol and SF36 from enrollment to 12 weeks. RESULTS: The prevalence of RVH and RVSD were 12.8% and 18.6%, respectively. RVSP was measurable in 71/119 subjects, 60%; mean RVSP was 42.5 mmHg. In the subgroup of subjects with RVSD, sildenafil-treated subjects experienced less decrement in 6MWD (99.3 meters, p=0.01) and greater improvement in SGRQ (13.4 points, p=0.005) and EuroQol visual analog scores (17.9 points, p=0.04) than placebo-treated subjects. In the subgroup with RVH, sildenafil was not associated with change in 6MWD (p=0.13), but was associated with greater relative improvement in SGRQ (14.8 points, p=0.02) versus placebo-treated subjects. Sildenafil treatment in those with RVSD and RVH was not associated with change in SF36. CONCLUSIONS: Sildenafil treatment in IPF with RVSD results in better preservation of exercise capacity as compared to placebo; sildenafil also improves quality of life in subjects with RVH and RVSD.
Chest 01/2013; · 5.25 Impact Factor
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MeiLan K Han,
Jeffrey Swigris,
Lyrica Liu,
Brian Bartholmai,
Susan Murray,
Nicholas Giardino,
Bruce Thompson,
Margaret Frederick,
Daner Li,
Marvin Schwarz,
Andrew Limper, Kevin Flaherty,
Fernando J Martinez
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ABSTRACT: HRQL in IPF patients is impaired. Data from other respiratory diseases led us to hypothesize that significant gender differences in HRQL in IPF also exist.
Data were drawn from the NIH-sponsored Lung Tissue Research Consortium (LTRC). Demographic and pulmonary physiology data along with MMRC, SF-12, and SGRQ scores from women vs. men were compared with two-sample t-tests. Multivariate linear regression was used to examine the association between SF-12 component scores and gender while adjusting for other relevant variables.
The study sample consisted of 147 men and 74 women. Among several baseline variables, only DL(CO)% predicted differed between women and men, (43.7 vs. 38.0, p=0.03). In general, men exhibited lower (better) MMRC scores (1.7 vs. 2.4, p=0.02), particularly those with milder disease as measured by DL(CO)% predicted. In an adjusted analysis, SF-12 PCS scores in men were lower (worse) than women (p=0.01), an effect that was more pronounced in men with greater dyspnea scores. In a similar analysis, SF-12 MCS scores in women were lower than men (worse) (48.3 vs. 54.4, p=0.0004), an effect that was more pronounced in women with greater dyspnea scores.
Significant gender differences in HRQL exist in IPF. As compared to women, men reported less severe dyspnea, had worse SF-12 PCS scores, but better SF-12 MCS scores. Dyspnea appears to have a greater impact on the physical HRQL of men and the emotional HRQL of women. An improved understanding of the mechanism behind these differences is needed to better target interventions.
Respiratory medicine 05/2010; 104(5):724-30. · 2.33 Impact Factor
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ABSTRACT: The clinical course of patients with idiopathic pulmonary fibrosis (IPF) is generally marked by a decline in pulmonary function over time. Increasingly, patients have been recognized as having an acute, and often fatal, clinical deterioration, termed an acute exacerbation of IPF (AE-IPF).
Review of the current literature pertaining to AE-IPF.
Acute exacerbations are defined by an acute onset of dyspnea (<1 month) with worsening hypoxia and progressive infiltrates seen in the absence of heart failure or infection. New ground-glass infiltrates are seen on chest CT scans with diffuse alveolar damage superimposed on a background of usual interstitial pneumonia that is evident on histopathology. The incidence is unknown and is impeded by difficulties in eliminating infection as a cause, as well as by reporting biases contained in reported series introduced by including only biopsied patients or only deaths, or by excluding patients with advanced disease. Prognosis is poor but may be influenced by diagnostic inaccuracy. Treatment with antiinflammatory therapies, such as corticosteroids, or with anticoagulation are unproven and have not as yet been fully studied.
AE of IPF is a complication that demands additional careful study to clarify its relationship to the clinical course of patients with IPF.
Chest 11/2007; 132(5):1652-8. · 5.25 Impact Factor
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ABSTRACT: Diffuse parenchymal lung diseases are a group of disorders that involve the space between the epithelial and endothelial basement membranes and are generally segregated into four major categories. These include the idiopathic interstitial pneumonias, which are further categorized into seven clinical/radiologic/pathologic subsets. These disorders generally share a common pattern of physiologic abnormality characterized by a restrictive ventilatory defect and reduced diffusing capacity (DLCO). Pulmonary function testing is often used and recommended in their assessment and management. The potential clinical application of physiologic testing includes to aid in diagnosis, although its value in differential diagnosis is limited. Pulmonary function testing also aids in establishing disease severity and in defining prognosis. In nonspecific interstitial pneumonia and idiopathic pulmonary fibrosis, severely decreased DLCO has proven valuable in this regard. Similarly, exertional desaturation to less than 88% at baseline testing and a decrease in FVC (greater than 10%) over the course of short-term follow-up identify patients at particular risk of mortality. Finally, physiologic testing, especially spirometry and DLCO, have demonstrated value in monitoring response to therapy and identifying disease progression.
Proceedings of the American Thoracic Society 07/2006; 3(4):315-21.
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ABSTRACT: Over the past several years, the significance of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in patients with chronic airflow obstruction has become increasingly apparent due to the impact these episodes have on the natural history of disease. It is now known that frequent AECOPD can adversely affect a patient's health-related quality of life and short- and long-term pulmonary function. The economic burden of these episodes is also substantial. AECOPDs represent a local and systemic inflammatory response to both infectious and noninfectious stimuli, but the majority of episodes are likely related to bacterial or viral pathogens. Patients with purulent sputum and multiple symptoms are the most likely to benefit from treatment with antibiotics. Antibiotic choice should be tailored to the individual patient, taking into account the severity of the episode and host factors which might increase the likelihood of treatment failure. Current evidence suggests that therapeutic goals not only include resolution of the acute episode, but also prolonging the time to the next event. In the future, preventing exacerbations will likely become increasingly accepted as an additional therapeutic goal in chronic obstructive pulmonary disease patients.
Expert Review of Anticancer Therapy 03/2006; 4(1):101-24. · 3.28 Impact Factor
