Lymphangioleiomyomatosis Diagnosis and Management: High-Resolution Chest Computed Tomography, Transbronchial Lung Biopsy, and Pleural Disease Management. An Official American Thoracic Society/Japanese Respiratory Society Clinical Practice Guideline.

Background: Recommendations regarding key aspects related to the diagnosis and pharmacological treatment of lymphangioleiomyomatosis (LAM) were recently published. We now provide additional recommendations regarding four specific questions related to the diagnosis of LAM and management of pneumothoraces in patients with LAM.

Methods: Systematic reviews were performed and then discussed by a multidisciplinary panel.

Heme Oxygenase-1 Deficiency Diminishes Methicillin-Resistant Staphylococcus aureus Clearance Due to Reduced TLR9 Expression in Pleural Mesothelial Cells.

Methicillin Resistant Staphylococcus aureus (MRSA) cause pneumonia and empyema thoraces. TLR9 activation provides protection against bacterial infections and Heme oxygenase-1 (HO-1) is known to enhance host innate immunity against bacterial infections. However, it is still unclear whether HO-1 regulates TLR-9 expression in the pleura and modulates the host innate defenses during MRSA empyema.

Official American Thoracic Society/Japanese Respiratory Society Clinical Practice Guidelines: Lymphangioleiomyomatosis Diagnosis and Management.

Background: Lymphangioleiomyomatosis (LAM) is a rare cystic lung disease that primarily affects women. The purpose of these guidelines is to provide recommendations for the diagnosis and treatment of LAM.

Methods: Systematic reviews were performed to summarize evidence pertinent to our questions.

Pleural Fluid Analysis in Chronic Hemothorax: A Mimicker of Infection.

Objectives: Timing to video-assisted thoracoscopic surgery (VATS) in hemothorax is based on preventing acute and long-term complications of retained blood products in the pleural space, including pleural space infection. We propose that the persistence of blood in the pleural space induces a proinflammatory state, independent of active infection.

Methods: We identified six patients with a hemothorax by clinical history, radiographic imaging, and pleural fluid analysis from a database of 1133 patients undergoing thoracentesis from 2002 to 2010 at the Medical University of South Carolina.

Validation of test performance characteristics and minimal clinically important difference of the 6-minute walk test in patients with idiopathic pulmonary fibrosis.

Background: The 6-minute walk test distance (6MWD) has been shown to be a valid and responsive outcome measure in patients with idiopathic pulmonary fibrosis (IPF). The analyses were based, however, on a single phase 3 trial and require validation in an independent cohort.

Objective: To confirm the performance characteristics and estimates of minimal clinically important difference (MCID) of 6MWD in an independent cohort of patients with IPF.

Sensitivity Analyses of the Change in FVC in a Phase 3 Trial of Pirfenidone for Idiopathic Pulmonary Fibrosis.

Background: FVC outcomes in clinical trials on idiopathic pulmonary fibrosis (IPF) can be substantially influenced by the analytic methodology and the handling of missing data. We conducted a series of sensitivity analyses to assess the robustness of the statistical finding and the stability of the estimate of the magnitude of treatment effect on the primary end point of FVC change in a phase 3 trial evaluating pirfenidone in adults with IPF.

Methods: Source data included all 555 study participants randomized to treatment with pirfenidone or placebo in the Assessment of Pirfenidone to Confirm Efficacy and Safety in Idiopathic Pulmonary Fibrosis (ASCEND) study.

Analysis of lung function and survival in RECAP: An open-label extension study of pirfenidone in patients with idiopathic pulmonary fibrosis.

Background: RECAP is an open-label extension study evaluating pirfenidone in patients with idiopathic pulmonary fibrosis (IPF) who completed the Phase 3 CAPACITY program.

Objective: We examined the effect of pirfenidone on lung function and survival in patients who were previously randomised to the placebo group in one of the two CAPACITY studies and received pirfenidone for the first time in RECAP.

Methods: Eligible patients received oral pirfenidone 2403 mg/day.

Characteristics of patients with yellow nail syndrome and pleural effusion.

Yellow nail syndrome (YNS) can be associated with a pleural effusion (PE) but the characteristics of these patients are not well defined. We performed a systematic review across four electronic databases for studies reporting clinical findings, PE characteristics, and most effective treatment of YNS. Case descriptions and retrospective studies were included, unrestricted by year of publication.

Comprehensive assessment of the long-term safety of pirfenidone in patients with idiopathic pulmonary fibrosis.

Background And Objective: Pirfenidone is an oral antifibrotic agent that is approved in several countries for the treatment of idiopathic pulmonary fibrosis (IPF). We performed a comprehensive analysis of safety across four clinical trials evaluating pirfenidone in patients with IPF.

Methods: All patients receiving pirfenidone 2403 mg/day in the Phase 3 CAPACITY studies (Studies 004 and 006) and all patients receiving at least one dose of pirfenidone in one of two ongoing open-label studies in patients with IPF (Studies 002 and 012) were selected for inclusion.

A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis.

Background: In two of three phase 3 trials, pirfenidone, an oral antifibrotic therapy, reduced disease progression, as measured by the decline in forced vital capacity (FVC) or vital capacity, in patients with idiopathic pulmonary fibrosis; in the third trial, this end point was not achieved. We sought to confirm the beneficial effect of pirfenidone on disease progression in such patients.

Methods: In this phase 3 study, we randomly assigned 555 patients with idiopathic pulmonary fibrosis to receive either oral pirfenidone (2403 mg per day) or placebo for 52 weeks.

All-cause mortality rate in patients with idiopathic pulmonary fibrosis. Implications for the design and execution of clinical trials.

Rationale: FVC has emerged as a standard primary endpoint in clinical trials evaluating novel therapies for patients with idiopathic pulmonary fibrosis (IPF). However, it has recently been proposed that all-cause mortality or a composite comprised of all-cause mortality and all-cause nonelective hospitalization be adopted as the standard primary endpoint for IPF clinical trials.

Objectives: To conduct a comprehensive evaluation of mortality in three phase 3 clinical trials and evaluate the feasibility of mortality trials in patients with IPF.

6-Minute walk distance is an independent predictor of mortality in patients with idiopathic pulmonary fibrosis.

6-min walk distance (6MWD) has recently been shown to be associated with the risk of mortality in patients with idiopathic pulmonary fibrosis (IPF); however, the independent contribution of 6MWD to the prediction of mortality risk has not been evaluated in a large, well-defined population of patients with IPF. A Cox proportional hazards model was used to characterise the relationship between risk factors of interest and all-cause mortality in IPF patients who completed a week 24 study visit in a clinical trial evaluating interferon γ-1b (n=748). Risk factors of interest included the independent predictors of mortality in the previously published clinical prediction model together with 6MWD and 24-week change in 6MWD.

Improving the predictive accuracy of identifying exudative effusions.

Background: Application of Light's criteria results in misclassification of some transudative effusions as exudative, particularly because of congestive heart failure (CHF). We sought to determine if the serum to pleural fluid albumin (SF-A) and serum to pleural fluid protein (SF-P) gradients increased the predictive accuracy to correctly identify exudative effusions.

Methods: We retrospectively analyzed 1,153 consecutive patients who underwent a diagnostic thoracentesis at the Medical University South Carolina.

Viral diseases affecting the pleura.

Background: Viruses affect the human body in multiple ways producing various disease states. The infections of the pulmonary parenchyma have been well described. However, there has been no current review of the literature pertaining to the pleura.

Can tuberculous pleural effusions be diagnosed by pleural fluid analysis alone?

Objective: To assess whether pleural fluid analysis (PFA) can confidently diagnose tuberculous pleural effusion (TPE).

Methods: PFA of 548 TPEs was performed between January 1991 and December 2011. The control group consisted of patients with malignant PE (MPE), complicated parapneumonic/empyema (infectious) PE (IPE), miscellaneous PE (MisPE) and transudative PE (TrPE).

Effects of coexisting pneumonia and end-stage renal disease on pleural fluid analysis in patients with hydrostatic pleural effusion.

Background: In individual patients, especially those who are hospitalized, several conditions often coexist that may be responsible for the development of a pleural effusion and may affect the pleural fluid analysis (PFA). The objective of this study was to investigate the effects of end-stage renal disease and pneumonia on PFA in patients with hydrostatic pleural effusion.

Methods: In a retrospective analysis of 1,064 consecutive patients who underwent thoracentesis at a university hospital, cell counts and pleural fluid protein, lactate dehydrogenase, pH, and glucose levels were examined in those (n = 300) with clinical evidence of hydrostatic pleural effusion.

Parasitic diseases of the pleura.

Parasitic infections are prevalent in certain parts of the world and may cause pleural involvement, which often goes unrecognized. Common parasites involving the pleura include Entamoeba histolytica, Echinococcus granulosus and Paragonimus westermani. Amebiasis can cause empyema with "anchovy sauce" pus, reactive pleural effusions and bronchopleural fistula with hydropneumothorax.

Unusual bacterial infections and the pleura.

Rickettsiosis, Q fever, tularemia, and anthrax are all bacterial diseases that can affect the pleura. Rocky Mountain Spotted Fever (RMSF) and Mediterranean Spotted Fever (MSF) are caused by Rickettsia rickettsii and Rickettsia conorii, respectively. Pleural fluid from a patient with MSF had a neutrophil-predominant exudate.

Getting the most from pleural fluid analysis.

Virtually, every pulmonary disease and most non-pulmonary diseases may be associated with a pleural effusion. The presence of a pleural effusion allows the clinician to 'diagnose' or narrow the differential diagnosis and aetiology of the fluid collection. However, pleural fluid analysis (PFA) in isolation rarely provides a definitive diagnosis.

Forced vital capacity in patients with idiopathic pulmonary fibrosis: test properties and minimal clinically important difference.

Rationale: Forced vital capacity (FVC) is an established measure of pulmonary function in idiopathic pulmonary fibrosis (IPF). Evidence regarding its measurement properties and minimal clinically important difference (MCID) in this population is limited.

Objectives: To assess the reliability, validity, and responsiveness of FVC and estimate the MCID in patients with IPF.

Intrapleural therapy.

Numerous intrapleural therapies have been adopted to treat a vast array of pleural diseases. The first intrapleural therapies proposed focused on the use of fibrinolytics and DNase to promote fluid drainage in empyema. Numerous case series and five randomized controlled trials have been published to determine the outcomes of fibrinolytics in empyema treatment.

Ascertainment of individual risk of mortality for patients with idiopathic pulmonary fibrosis.

Rationale: Several predictors of mortality in patients with idiopathic pulmonary fibrosis have been described; however, there is a need for a practical and accurate method of quantifying the prognosis of individual patients.

Objectives: Develop a practical mortality risk scoring system for patients with idiopathic pulmonary fibrosis.

Methods: We used a Cox proportional hazards model and data from two clinical trials (n = 1,099) to identify independent predictors of 1-year mortality among patients with idiopathic pulmonary fibrosis.

Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials.

Background: Idiopathic pulmonary fibrosis is a progressive and fatal lung disease with inevitable loss of lung function. The CAPACITY programme (studies 004 and 006) was designed to confirm the results of a phase 2 study that suggested that pirfenidone, a novel antifibrotic and anti-inflammatory drug, reduces deterioration in lung function in patients with idiopathic pulmonary fibrosis.

Methods: In two concurrent trials (004 and 006), patients (aged 40-80 years) with idiopathic pulmonary fibrosis were randomly assigned to oral pirfenidone or placebo for a minimum of 72 weeks in 110 centres in Australia, Europe, and North America.