A controlled trial of sildenafil in advanced idiopathic pulmonary fibrosis.

BACKGROUND: Sildenafil, a phosphodiesterase-5 inhibitor, may preferentially improve blood flow to well-ventilated regions of the lung in patients with advanced idiopathic pulmonary fibrosis, which could result in improvements in gas exchange. We tested the hypothesis that treatment with sildenafil would improve walk distance, dyspnea, and quality of life in patients with advanced idiopathic pulmonary fibrosis, defined as a carbon monoxide diffusion capacity of less than 35% of the predicted value. METHODS: We conducted a double-blind, randomized, placebo-controlled trial of sildenafil in two periods. The first period consisted of 12 weeks of a double-blind comparison between sildenafil and a placebo control. The primary outcome was the proportion of patients with an increase in the 6-minute walk distance of 20% or more. Key secondary outcomes included changes in oxygenation, degree of dyspnea, and quality of life. The second period was a 12-week open-label evaluation involving all patients receiving sildenafil. RESULTS: A total of 180 patients were enrolled in the study. The difference in the primary outcome was not significant, with 9 of 89 patients (10%) in the sildenafil group and 6 of 91 (7%) in the placebo group having an improvement of 20% or more in the 6-minute walk distance (P=0.39). There were small but significant differences in arterial oxygenation, carbon monoxide diffusion capacity, degree of dyspnea, and quality of life favoring the sildenafil group. Serious adverse events were similar in the two study groups. CONCLUSIONS: This study did not show a benefit for sildenafil for the primary outcome. The presence of some positive secondary outcomes creates clinical equipoise for further research. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov number, NCT00517933.)

Screening Strategies for Pulmonary Hypertension in Patients With Interstitial Lung Disease: A Multidisciplinary Delphi Study.

BACKGROUND: Pulmonary hypertension (PH) is a common complication of interstitial lung disease (ILD) and is associated with worse outcomes and increased mortality. Evaluation of PH is recommended in lung transplant candidates, but there are currently no standardized screening approaches. Trials have identified therapies that are effective in this setting, providing another rationale to routinely screen patients with ILD for PH. RESEARCH QUESTION: What screening strategies for identifying PH in patients with ILD are supported by expert consensus? STUDY DESIGN AND METHODS: The study convened a panel of 16 pulmonologists with expertise in PH and ILD, and used a modified Delphi consensus process with three surveys to identify PH screening strategies. Survey 1 consisted primarily of open-ended questions. Surveys 2 and 3 were developed from responses to survey 1 and contained statements about PH screening that panelists rated from -5 (strongly disagree) to 5 (strongly agree). RESULTS: Panelists reached consensus on several triggers for suspicion of PH including the following: symptoms, clinical signs, findings on chest CT scan or other imaging, abnormalities in pulse oximetry, elevations in brain natriuretic peptide (BNP) or N-terminal pro-brain natriuretic peptide (NT-proBNP), and unexplained worsening in pulmonary function tests or 6-min walk distance. Echocardiography and BNP/NT-proBNP were identified as screening tools for PH. Right heart catheterization was deemed essential for confirming PH. INTERPRETATION: Many patients with ILD may benefit from early evaluation of PH now that an approved therapy is available. Protocols to evaluate patients with ILD often overlap with evaluations for pulmonary hypertension-interstitial lung disease and can be used to assess the risk of PH. Because standardized approaches are lacking, this consensus statement is intended to aid physicians in the identification of patients with ILD and possible PH, and provide guidance for timely right heart catheterization.

Diagnosis and hemodynamic assessment of pulmonary arterial hypertension.

Pulmonary hypertension (PH) can occur as either a primary or a secondary process, and in general, its presence increases overall morbidity and mortality. Importantly, the majority of prior studies have been in the setting of idiopathic pulmonary arterial hypertension (IPAH); thus the following discussion focuses on IPAH. Because the majority of available diagnostic strategies lack sensitivity and specificity, the physician must maintain a high index of suspicion in considering PAH. This article provides an overview of the available diagnostic studies for PAH with a particular focus on hemodynamic assessment. Novel approaches to the often delayed diagnosis of PAH are being studied and are also discussed here.

Validation of a method to screen for pulmonary hypertension in advanced idiopathic pulmonary fibrosis.

BACKGROUND: We have developed a method to screen for pulmonary hypertension (PH) in idiopathic pulmonary fibrosis (IPF) patients, based on a formula to predict mean pulmonary artery pressure (MPAP) from standard lung function measurements. The objective of this study was to validate this method in a separate group of IPF patients. METHODS: Cross-sectional study of 60 IPF patients from two institutions. The accuracy of the MPAP estimation was assessed by examining the correlation between the predicted and measured MPAPs and the magnitude of the estimation error. The discriminatory ability of the method for PH was assessed using the area under the receiver operating characteristic curve (AUC). RESULTS: There was strong correlation in the expected direction between the predicted and measured MPAPs (r = 0.72; p < 0.0001). The estimated MPAP was within 5 mm Hg of the measured MPAP 72% of the time. The AUC for predicting PH was 0.85, and did not differ by institution. A formula-predicted MPAP > 21 mm Hg was associated with a sensitivity, specificity, positive predictive value, and negative predictive value of 95%, 58%, 51%, and 96%, respectively, for PH defined as MPAP from right-heart catheterization > 25 mm Hg. CONCLUSIONS: A prediction formula for MPAP using standard lung function measurements can be used to screen for PH in IPF patients.

Right ventricular systolic pressure by echocardiography as a predictor of pulmonary hypertension in idiopathic pulmonary fibrosis.

RATIONALE: Pulmonary hypertension (PH) commonly complicates the course of patients with idiopathic pulmonary fibrosis (IPF). It has a significant impact on outcomes and is, therefore, important to detect. OBJECTIVES: We sought to characterize the accuracy and performance characteristics of the right ventricular systolic pressure (RVSP) as estimated by echocardiography (ECHO) alone and in conjunction with physiologic indices in predicting the presence of PH in IPF patients. METHODS: Cross-sectional study of IPF patients from two large tertiary centers in whom both ECHO and right-heart catheterization (RHC) were available. MEASUREMENTS AND MAIN RESULTS: There were 110 patients with available ECHOs and RHCs. Estimates of RVSP were reported in 60 of these patients (54.5%) of whom 22 (36.6%) had PH, while 16 of the 50 patients without RVSP estimate (32%) had PH. Twenty-four of 60 (40%) ECHOs accurately reflected the pulmonary arterial systolic pressure as measured by RHC. An optimal RVSP threshold for the screening of PH could not be detected. When assessed in combination with various thresholds of PFT and 6-minute walk test (6MWT) parameters, the performance characteristics of the RVSP were slightly improved. CONCLUSION: The RVSP is not an accurate test for the assessment of PH in IPF patients. Awareness of the various combinations of threshold values for RVSP with and without PFT and 6MWT might nonetheless assist clinicians in risk stratifying IPF patients for the presence of PH.

Retrospective study of pulmonary function tests in patients presenting with isolated reduction in single-breath diffusion capacity: implications for the diagnosis of combined obstructive and restrictive lung disease.

OBJECTIVE: To examine the frequency and spectrum of diseases associated with isolated reduction in the diffusing capacity of lung for carbon monoxide (D(Lco)). PATIENTS AND METHODS: We retrospectively identified all potentially dyspneic patients who had pulmonary function tests (PFTs) performed at the Mayo Clinic in Jacksonville, Fla, between January 1, 1990, and June 30, 2000, that showed reduced D(Lco) (< 70% of predicted), normal lung volumes (total lung capacity and residual volume > 80% and < 120% of predicted, respectively), and airflow variables (forced expiratory volume in 1 second and forced vital capacity values > 80% of predicted and forced expiratory volume in 1 second/forced vital capacity ratio > 70% of predicted). Only patients who had also undergone chest computed tomography (CT) and echocardiography within 1 month of PFTs were studied. RESULTS: Of the 38,095 patients who underwent PFTs during the study period, 179 (0.47%; 95% confidence interval [CI], 0.40%-0.54%) had isolated D(Lco) abnormalities. The 27 patients (15.1%; 95% CI, 10.2%-21.2%) who had also undergone chest CT and echocardiography within 1 month of PFTs form the study cohort reported herein. Their mean D(Lco) was 50% +/- 15% (95% CI, 45%-56%) with average normal pulse oxygen saturation at rest and mild hypoxemia with activity. Thirteen of the 27 patients (48%; 95% CI, 28.7%-68.1%) had underlying emphysema evident on CT. Eleven of these 13 patients had emphysema associated with a restrictive lung process. The 14 patients without emphysema had interstitial lung disease, pulmonary vascular disease, and other isolated findings. Six patients with combined emphysema and idiopathic pulmonary fibrosis accounted for the largest percentage (22%) of patients with Isolated D(Lco) reduction. The mean +/- SD smoking history of the 27 patients in the study cohort was 36 +/- 33 pack-years (range, 0-116 pack-years). CONCLUSION: Dyspneic patients with respiratory symptoms and normal lung volumes and airflows associated with Isolated reduction in D(Lco) should be evaluated for underlying diseases such as emphysema, with or without a concomitant restrictive process, and pulmonary vascular disease.

Sildenafil improves walk distance in idiopathic pulmonary fibrosis.

Pulmonary hypertension is a common finding in patients with idiopathic pulmonary fibrosis (IPF), and is associated with increased morbidity and mortality. Therapy with sildenafil has been shown to decrease pulmonary vascular resistance in patients with pulmonary fibrosis and may improve functional status. Patients with IPF and documented pulmonary hypertension were followed up in an open-label study of sildenafil. The 6-min walk test distance (6MWD) was obtained before and after 3 months of sildenafil therapy. Fourteen patients were followed up in the study; 11 patients completed both 6-min walk tests. The mean improvement in walk distance was 49.0 m (90% confidence interval, 17.5 to 84.0 m). When all 14 patients were dichotomized into groups of "responders" (ie, >/= 20% improvement in 6MWD) or "nonresponders" (ie, < 20% change or unable to complete), 57% were classified as responders. Sildenafil is a promising and well-tolerated therapeutic agent for use in patients with IPF and pulmonary hypertension, and should be studied in a large, well-controlled trial.

High-resolution chest CT findings do not predict the presence of pulmonary hypertension in advanced idiopathic pulmonary fibrosis.

BACKGROUND: Reliable, noninvasive approaches to the diagnosis of pulmonary hypertension (PH) in patients with idiopathic pulmonary fibrosis (IPF) are needed. We tested the hypothesis that chest CT-determined extent of pulmonary fibrosis and/or main pulmonary artery diameter (MPAD) can be used to identify the presence of PH in patients with advanced IPF. METHODS: Cross-sectional study of 65 patients with advanced IPF and available right-heart catheterization and high-resolution chest CT. An expert radiologist scored ground-glass opacity, lung fibrosis, and honeycombing in the CT images on a scale of 0 to 4. These scores were also summed into a total profusion score. The main pulmonary artery was measured at its widest dimension on the supine full-chest sequence. At this same level, the widest aorta diameter was measured. RESULTS: Chest CT-determined fibrosis score, ground-glass opacity score, honeycombing score, total profusion score, diameter of the main pulmonary artery, and the ratio of the pulmonary artery to aorta diameter did not differ between those with and without PH. There was no significant correlation between mean pulmonary artery pressure and any of the chest CT-determined measures. CONCLUSIONS: High-resolution chest CT-determined extent of pulmonary fibrosis and/or MPAD cannot be used to screen for PH in advanced IPF patients.

Prediction of pulmonary hypertension in idiopathic pulmonary fibrosis.

BACKGROUND: Reliable, noninvasive approaches to the diagnosis of pulmonary hypertension in idiopathic pulmonary fibrosis are needed. We tested the hypothesis that the forced vital capacity to diffusing capacity ratio and room air resting pulse oximetry may be combined to predict mean pulmonary artery pressure (MPAP) in idiopathic pulmonary fibrosis. METHODS: Sixty-one idiopathic pulmonary fibrosis patients with available right-heart catheterization were studied. We regressed measured MPAP as a continuous variable on pulse oximetry (SpO(2)) and percent predicted forced vital capacity (FVC) to percent-predicted diffusing capacity ratio (% FVC/% DL(co)) in a multivariable linear regression model. RESULTS: Linear regression generated the following equation: MPAP=-11.9+0.272 x SpO(2)+0.0659 x (100-SpO(2))(2)+3.06 x (% FVC/% DL(co)); adjusted R(2)=0.55, p<0.0001. The sensitivity, specificity, positive predictive and negative predictive value of model-predicted pulmonary hypertension were 71% (95% confidence interval (CI): 50-89%), 81% (95% CI: 68-92%), 71% (95% CI: 51-87%) and 81% (95% CI: 68-94%). CONCLUSIONS: A pulmonary hypertension predictor based on room air resting pulse oximetry and FVC to diffusing capacity ratio has a relatively high negative predictive value. However, this model will require external validation before it can be used in clinical practice.

Utility of Transbronchial vs Surgical Lung Biopsy in the Diagnosis of Suspected Fibrotic Interstitial Lung Disease.

BACKGROUND: Surgical lung biopsy (SLB) is invasive and not possible in all patients with undiagnosed interstitial lung disease (ILD). We hypothesized that transbronchial biopsy (TBB) findings combined with clinical and high-resolution CT (HRCT) data leads to a confident diagnosis congruent to SLB and therefore avoids the need for SLB in some patients. METHODS: We evaluated 33 patients being investigated for suspected ILD who underwent HRCT, TBB, and SLB. First, clinicians, radiologists, and a pathologist reviewed the clinical information and HRCT and TBB findings. Clinicians were asked to provide a diagnosis and were also asked if SLB was needed for a more confident diagnosis. Subsequently, the clinical, HRCT, and SLB data were reviewed, and the same participants were asked to provide a final diagnosis. Clinician consensus and overall agreement between TBB- and SLB-based diagnoses were calculated. RESULTS: Four patients had definite usual interstitial pneumonia (UIP) on HRCT and would not be considered for biopsy using current guidelines. Of the 29 patients without a definitive HRCT diagnosis, the clinicians felt confident of the diagnosis (ie, would not recommend SLB) in six cases. In these cases, there was 100% agreement between TBB and SLB diagnoses. UIP was the most common diagnosis (n = 3) and was associated with an HRCT diagnosis of possible UIP/nonspecific interstitial pneumonia-like. Agreement was poor (33%) between TBB and SLB diagnoses when confidence in the TBB diagnosis was low. CONCLUSIONS: Information from TBB, when combined with clinical and HRCT data, may provide enough information to make a confident and accurate diagnosis in approximately 20% to 30% of patients with ILD.

Transbronchial biopsy in usual interstitial pneumonia.

BACKGROUND: Usual interstitial pneumonia (UIP) is a slowly progressive, usually fatal form of idiopathic interstitial pneumonia for which there is no effective treatment. Transbronchial biopsy (TBB) has been utilized only to exclude other diseases such as sarcoidosis, lymphangitic carcinoma, and infection, for example, but TBB is generally considered to have little role in confirming UIP. OBJECTIVE: To determine whether diagnostic changes of UIP can be appreciated on TBB specimens. DESIGN: Retrospective analysis of TBB specimens from patients with proven UIP. SETTING: Two study sites in the United States. PARTICIPANTS: Twenty-one patients with UIP confirmed by surgical lung biopsy and/or lung explant, and 1 patient with UIP confirmed by clinical and radiographic findings along with follow-up information. MEASUREMENTS AND RESULTS: Adequate tissue for diagnosis was available in 18 cases; in 7 cases (32% overall), there were varying combinations of interstitial fibrosis in a patchwork pattern along with fibroblast foci and/or honeycomb change. These features were considered diagnostic of UIP. Interstitial fibrosis along with fibroblast foci or honeycomb change were seen in two other cases, but the fibrosis lacked a patchwork pattern, and these features were considered consistent with UIP. Nonspecific interstitial fibrosis alone was found in nine cases. CONCLUSIONS: In summary, characteristic histologic features of UIP can be identified on TBB specimens more often than previously appreciated. TBB may be more useful in confirming UIP than previously recognized.

Pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing lung disease limited to the lungs and associated with the histologic appearance of usual interstitial pneumonia (UIP) on surgical lung biopsy. The estimated prevalence in the United States is between 35,000 and 55,000 cases,and evidence suggests that the prevalence is increasing for IPF. Risk factors associated with pulmonary fibrosis include smoking, environmental exposures, gastroesophageal reflux dis-ease, commonly prescribed drugs, diabetes mellitus, infectious agents, and genetic factors. The diagnosis requires a careful history and physical examination, characteristic physiological and radiological studies, and, in some cases, a surgical lung biopsy. The natural history of IPF is not known, but evidence supports the concept of a continuum of idiopathic interstitial pneumonias that may overlap in time. Most patients with IPF succumb to respiratory failure, cardiovascular disease, lung cancer, pulmonary embolism, infection, and other health problems. The median survival time for patients with IPF is less than 3 yr. Factors that predict poor outcome include older age, male gender, severe dyspnea, history of cigarette smoking, severe loss of lung function, appearance and severity of fibrosis on radiological studies, lack of response to therapy,and prominent fibroblastic foci on histopathologic evaluation. Conventional therapy (corticosteroids, azathioprine, cyclophosphamide) provides only marginal benefit. Lung transplantation should be considered for patients with IPF refractory to medical therapy. In light of the poor prognosis and lack of response to available anti-inflammatory therapy, alternative approaches to therapy are being pursued. Emerging strategies to treat patients with IPF include agents that inhibit epithelial injury or enhance repair, anti-cytokine approaches, agents that inhibit fibroblast proliferation or induce fibroblast apoptosis, and other novel approaches.

Association between pulmonary fibrosis and coronary artery disease.

BACKGROUND: Pulmonary fibrosis and atherosclerosis have many similarities at the histopathologic level. Moreover, fibrotic lung diseases exhibit systemic effects and have the potential to affect the vasculature beyond the lung. The existence of a relationship between the two, however, has not been studied. METHODS: To investigate whether fibrotic lung disorders may predispose to atherosclerosis, we conducted a cross-sectional study of 630 patients referred for lung transplantation evaluation at a university hospital. We compared the prevalence of angiographic coronary artery disease (CAD) in patients with fibrotic vs nonfibrotic lung diseases. RESULTS: Fibrotic lung diseases were associated with an increased prevalence of CAD compared with nonfibrotic diseases after adjustment for traditional risk factors (odds ratio, 2.18; 95% confidence interval, 1.17-4.06). The magnitude and significance of this association were maintained when only nongranulomatous fibrotic disease or its subset, idiopathic pulmonary fibrosis, was examined. The strength of the relationship between fibrotic disorders and CAD increased when multivessel disease was analyzed (odds ratio, 4.16; 95% confidence interval, 1.46-11.9). No significant association was detected for granulomatous fibrotic disorders (odds ratio, 1.56; 95% confidence interval, 0.47-5.16; P =.47), although this subgroup had fewer cases of CAD for analysis. CONCLUSIONS: These findings support an association between fibrotic lung disorders and CAD. Further research is necessary to confirm this relationship and to explore the pathologic processes underlying, and potentially linking, these 2 conditions.

Usual interstitial pneumonia: histologic study of biopsy and explant specimens.

The pathologic findings in biopsy and subsequent explant specimens from 20 patients with usual interstitial pneumonia (UIP) were reviewed to refine histologic criteria for diagnosis, to identify factors that may confound diagnosis, and to assess the relationship of UIP and nonspecific interstitial pneumonia (NSIP). One case of NSIP was also identified and included for comparison. Surgical biopsies from 15 of the 20 UIP cases were diagnosed as UIP, whereas 5 showed only nondiagnostic changes. An important new observation is that areas resembling nonspecific interstitial pneumonia (NSIP-like areas) are present in the majority of UIP cases in both biopsy and explant specimens, and they are extensive in some. Ten of the 15 UIP biopsies were considered straightforward, with typical patchy interstitial fibrosis, honeycomb change, and fibroblast foci. Five cases were considered difficult because of prominent NSIP-like areas in two, extensive honeycomb change in one, superimposed diffuse alveolar damage in one, and superimposed bronchiolitis obliterans-organizing pneumonia in one. The most helpful feature for diagnosing UIP in difficult cases was the presence of a distinct patchwork appearance to the characteristic uneven or variegated parenchymal involvement along with evidence of architectural derangement. No explant showing UIP was preceded by biopsy findings of NSIP, and the one NSIP case appeared similar at biopsy and explant. NSIP or NSIP-like areas and UIP may reflect different mechanisms of fibrosis related either to different severity of injury or to different injuries.

Idiopathic pulmonary fibrosis: pathogenesis and therapeutic approaches.

Idiopathic pulmonary fibrosis (IPF), also termed cryptogenic fibrosing alveolitis, is a clinicopathological syndrome characterised by cough, exertional dyspneoa, basilar crackles, a restrictive defect on pulmonary function tests, honeycombing on high-resolution, thin-section computed tomographic scans and the histological diagnosis of usual interstitial pneumonia on lung biopsy. The course is usually indolent but inexorable. Most patients die of progressive respiratory failure within 3-8 years of the onset of symptoms. Current therapies are of unproven benefit. Although the pathogenesis of IPF has not been elucidated, early concepts focused on lung injury leading to a cycle of chronic alveolar inflammation eventuating in fibrosis and destruction of the lung architecture. Anti-inflammatory therapies employing corticosteroids or immunosuppressive or cytotoxic agents have been disappointing. More recent hypotheses acknowledge that sequential alveolar epithelial cell injury is likely to be a key event in the pathogenesis of IPF, but the cardinal event is an aberrant host response to wound healing. In this context, abnormal epithelial-mesenchymal interactions, altered fibroblast phenotypes, exaggerated fibroblast proliferation, and excessive deposition of collagen and extracellular matrix are pivotal to the fibrotic process. Several clinical trials are currently underway or in the planning stages, and include drugs such as interferon-gamma 1b, pirfenidone, acetylcysteine, etanercept (a tumor necrosis factor-alpha antagonist), bosentan (an endothelin-1 receptor antagonist) and zileuton (a 5-lypoxygenase inhibitor). Future therapeutic strategies should be focused on alveolar epithelial cells aimed at enhancing re-epithelialisation and on fibroblastic/myofibroblastic foci, which play an essential role in the development of IPF. Stem cell progenitors of the alveolar epithelial cells and genetic and epigenetic therapies are attractive future approaches for this and other fibrotic lung disorders.

Cardiopulmonary bypass for bilateral sequential lung transplantation in patients with chronic obstructive pulmonary disease without adverse effect on lung function or clinical outcome.

OBJECTIVE: The use of cardiopulmonary bypass in lung transplantation remains controversial. Previous studies have concluded that cardiopulmonary bypass is deleterious, but these studies were confounded by the inclusion of patients with different diagnoses undergoing single- and double-lung transplantation with elective or emergency use of bypass. The goal of this study was to determine whether cardiopulmonary bypass has deleterious effects on lung function or clinical outcome by analyzing the cases of patients with a single disease entity and elective use of bypass for bilateral sequential lung transplantation. METHODS: A retrospective review of 50 patients with chronic obstructive pulmonary disease who underwent bilateral sequential lung transplantation was performed. Fourteen patients who underwent elective cardiopulmonary bypass for 218.3 +/- 75.4 minutes were compared to 36 control patients. RESULTS: After the operation, the bypass and nonbypass groups were not significantly different with respect to median duration of mechanical ventilation (1 day vs 1 day, P =.76), median stay in the intensive care unit (4 days vs 4 days, P =.44), median hospital stay (15.5 days vs 16 days, P =.74), mean increase in serum creatinine level (1.4 +/- 1.9 mg/dL vs 0.9 +/- 1.0 mg/dL, P =.33), and mean ratio of Pao(2) to fraction of inspired oxygen at 1 hour (376.6 +/- 123 vs 357.0 +/- 218, P =.75), at 24 hours (309.9 +/- 92 vs 350.6 +/- 122, P =.26), and at 48 hours (335.0 +/- 144 vs 316.2 +/- 120, P =.64). Late outcome markers compared between the bypass and nonbypass groups were the following: 1-year percentage predicted forced expiratory volume in 1 second (76.1% +/- 17.0% vs 85.3% +/- 21.7%, P =.24), 30-day mortality (7.1% vs 8.3%, P >.999), 1-year survival (85.7% vs 80.1%, P =.66), 3-year survival (64.3% vs 58.3%, P =.70), and the prevalence of bronchiolitis obliterans syndrome (0% vs 36.1%, P =.01). CONCLUSION: Cardiopulmonary bypass appears to have no deleterious effect on early lung function or clinical outcome. We hope that this pilot study removes some of the unwarranted fear of the use of bypass in lung transplantation for chronic obstructive pulmonary disease.

Treprostinil to reverse pulmonary hypertension associated with idiopathic pulmonary fibrosis as a bridge to single-lung transplantation.

The available therapies and prognosis of idiopathic pulmonary fibrosis remain relatively poor, and concurrent pulmonary hypertension further increases the risk of death and complications after lung transplantation. Limited data exist for the treatment of pulmonary hypertension associated with idiopathic pulmonary fibrosis. We describe a case where intravenous treprostinil was used to bridge an elderly patient with idiopathic pulmonary fibrosis with severe pulmonary hypertension to successful single-lung transplantation.

Serum albumin concentration and waiting list mortality in idiopathic interstitial pneumonia.

BACKGROUND: Hypoalbuminemia is a reliable predictor of mortality in patients with various illnesses as well as a predictor of disability and mortality in healthy older adults. The association between hypoalbuminemia and mortality in patients with idiopathic interstitial pneumonia remains unknown. The objective of this study was to examine the relationship between serum albumin concentration and mortality in a large cohort of patients with idiopathic interstitial pneumonia listed for lung transplantation. METHODS: In patients classified as having idiopathic pulmonary fibrosis who were listed for lung transplantation with the United Network for Organ Sharing between January 1, 2004, and December 31, 2006 (n = 1,269), we studied the relationship between serum albumin concentration at the time of listing and mortality while awaiting transplantation. RESULTS: Lower serum albumin was associated with increased mortality rate. Patients with lower categories of serum albumin had increased mortality rates before and after multivariable adjustment (p value for linear trend < 0.0001). Analysis with serum albumin as a continuous predictor indicated that the mortality rate increased by 54% with each 0.5 g/dL decrease in serum albumin concentration (95% confidence interval, 32 to 79%). CONCLUSIONS: Lower serum albumin is strongly and independently associated with higher mortality in patients with idiopathic interstitial pneumonia on transplant waiting lists.

Idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF; also known as cryptogenic fibrosing alveolitis) is a distinctive type of chronic fibrosing interstitial pneumonia of unknown cause associated with the histological pattern usual interstitial pneumonia (UIP). UIP is a distinct histological pattern observed in IPF but may also be found in other etiologies. The diagnosis of UIP can be established by surgical lung biopsy or by high-resolution thin-section CT scans (provided the radiographic features are classical). Historically, patients labeled as 'IPF' encompassed a group of disorders, including UIP, as well as other idiopathic interstitial pneumonias, which differ from UIP in prognosis and responsiveness to therapy. The term IPF should be restricted to patients with idiopathic UIP. The inciting cause(s) and pathogenesis of IPF have not been elucidated but alveolar epithelial cell injury and dysregulation or altered phenotypic expression of fibroblasts are key elements. Inflammatory cells may play minor roles in initiating or propagating the fibrotic process. The prognosis of idiopathic UIP is poor. Mean survival following diagnosis approximates at 3 years. Current medical therapies are of unproven value. Lung transplantation is a viable option for patients failing medical therapy.