Background: This document provides clinical recommendations for the diagnosis of idiopathic pulmonary fibrosis (IPF). It represents a collaborative effort between the American Thoracic Society, Eur...

https://www.atsjournals.org/doi/pdf/10.1164/rccm.201807-1255ST

Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline.

The appropriate selection of lung transplant recipients is an important determinant of outcomes. This consensus document is an update of the recipient selection guidelines published in 2006. The Pulmonary Council of the International Society for Heart and Lung Transplantation (ISHLT) organized a Writing Committee of international experts to provide consensus opinion regarding the appropriate timing of referral and listing of candidates for lung transplantation. A comprehensive search of the medical literature was conducted with the assistance of a medical librarian. Writing Committee members were assigned specific topics to research and discuss. The Chairs of the Writing Committee were responsible for evaluating the completeness of the literature search, providing editorial support for the manuscript, and organizing group discussions regarding its content. The consensus document makes specific recommendations regarding the timing of referral and of listing for lung transplantation. These recommendations include discussions not present in previous ISHLT guidelines, including lung allocation scores, bridging to transplant with mechanical circulatory and ventilator support, and expanded indications for lung transplantation. In the absence of high-grade evidence to support decision making, these consensus guidelines remain part of a continuum of expert opinion based on available studies and personal experience. Some positions are immutable. Although transplant is rightly a treatment of last resort for end-stage lung disease, early referral allows proper evaluation and thorough patient education. Subsequent waiting list activation implies a tacit agreement that transplant offers a significant individual survival advantage. It is both the challenge and the responsibility of the transplant community globally to ensure organ allocation maximizes the potential benefits of a scarce resource, thereby achieving that advantage.

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A consensus document for the selection of lung transplant candidates: 2014-An update from the Pulmonary Transplantation Council of the International Society for Heart and Lung Transplantation

Fibrosis is a consequence of the inflammatory response. When fibrotic tissue becomes excessive, it can have diverse pathophysiological effects on a number of organ systems. The mechanisms underlying fibrosis and approaches to therapy are reviewed.

https://www.nejm.org/doi/suppl/10.1056/NEJMra1300575/suppl_file/nejmra1300575_appendix.pdf

Fibrosis — A Common Pathway to Organ Injury and Failure

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(17)30866-8.pdf

Idiopathic pulmonary fibrosis

Acute exacerbation of idiopathic pulmonary fibrosis has been defined as an acute, clinically significant, respiratory deterioration of unidentifiable cause. The objective of this international working group report on acute exacerbation of idiopathic pulmonary fibrosis was to provide a comprehensive update on the topic. A literature review was conducted to identify all relevant English text publications and abstracts. Evidence-based updates on the epidemiology, etiology, risk factors, prognosis, and management of acute exacerbations of idiopathic pulmonary fibrosis are provided. Finally, to better reflect the current state of knowledge and improve the feasibility of future research into its etiology and treatment, the working group proposes a new conceptual framework for acute respiratory deterioration in idiopathic pulmonary fibrosis and a revised definition and diagnostic criteria for acute exacerbation of idiopathic pulmonary fibrosis.

Acute Exacerbation of Idiopathic Pulmonary Fibrosis. An International Working Group Report

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. The primary end point was the change in FVC or death at week 52. Secondary end points were the 6-minute walk distance, progression-free survival, dyspnea, and death from any cause or from idiopathic pulmonary fibrosis. Results In the pirfenidone group, as compared with the placebo group, there was a relative reduction of 47.9% in the proportion of patients who had an absolute decline of 10 percentage points or more in the percentage of the predicted FVC or who died; there was also a relative increase of 132.5% in the proportion of patients with no decline in FVC (P<0.001). Pirfenidone reduced the decline in the 6-minute walk distance (P = 0.04) and improved progression-free survival (P<0.001). There was no significant between-group difference in dyspnea scores (P = 0.16) or in rates of death from any cause (P = 0.10) or from idiopathic pulmonary fibrosis (P = 0.23). However, in a prespecified pooled analysis incorporating results from two previous phase 3 trials, the between-group difference favoring pirfenidone was significant for death from any cause (P = 0.01) and from idiopathic pulmonary fibrosis (P = 0.006). Gastrointestinal and skin-related adverse events were more common in the pirfenidone group than in the placebo group but rarely led to treatment discontinuation. Conclusions Pirfenidone, as compared with placebo, reduced disease progression, as reflected by lung function, exercise tolerance, and progression-free survival, in patients with idiopathic pulmonary fibrosis. Treatment was associated with an acceptable sideeffect profile and fewer deaths. (Funded by InterMune; ASCEND ClinicalTrials.gov number, NCT01366209.)

/pdf/a-phase-3-trial-of-pirfenidone-in-patients-with-idiopathic-4d381vhpk1.pdf

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

Introduction: ASCEND is a Phase 3 trial evaluating pirfenidone in IPF. Design modifications (vs. CAP) included a 1 year treatment period; centralised procedures for diagnosis, spirometry, and mortality adjudication; and modification of eligibility criteria to enrol patients with greater risk for disease progression. Objective: Assess the effect of design modifications on IPF trial outcomes. Methods: Modified criteria for ASCEND included: IPF diagnosis ≥6 months prior to randomization (vs. no time limit in CAP); % predicted forced vital capacity (%FVC) ≥50% and ≤90% and % predicted carbon monoxide diffusing capacity (%DLco) ≥30% and ≤90% (vs. %FVC or %DLco ≤90% in CAP); and forced expiratory volume in 1 second (FEV 1 )/FVC ratio ≥0.80 (vs. ≥0.70 in CAP). Central review of HRCT scans and lung biopsies was implemented to minimiseheterogeneity. Results : Baseline characteristics in the ASCEND and CAP studies are summarized in Table 1 . Lower median values for %FVC and %DL CO and a longer median time since diagnosis were observed in ASCEND. Conclusions: Baseline characteristics in ASCEND were generally similar to those in CAP. Notable differences included lower %FVC and %DL CO and a longer time since diagnosis in ASCEND, each of which has been shown to be independently associated with a higher risk of FVC decline.

Socorro Castro-Bernardini

Papers

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

Effect of design modifications on trial outcomes in idiopathic pulmonary fibrosis (IPF): Analysis of data from ASCEND and CAPACITY (CAP)