Antacid Medication and Antireflux Surgery in Patients with Idiopathic Pulmonary Fibrosis A Systematic Review and Meta-Analysis

Rationale: Idiopathic pulmonary fibrosis (IPF) is a fibrosing interstitial pneumoniawith impaired survival. Previous guidelines recommend antacidmedication to improve respiratory outcomes in patientswith IPF. Objectives: This systematic review was undertaken during the development of an American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociacion Latinoamericana del Torax guideline. The clinical question was, "Should patients with IPF who have documented abnormal gastroesophageal reflux (GER) with or without symptoms of GER disease 1) be treated with antacidmedication or 2) undergo antireflux surgery to improve respiratory outcomes?"Methods: Medline, Embase, the Cochrane Central Register of Controlled Trials, and the gray literature were searched through June 30, 2020. Studies that enrolled patients with IPF and 1) compared antacid medication to placebo or no medication or 2) compared antireflux surgery to no surgery were selected. Metaanalyses were performed when possible. Outcomes included disease progression, mortality, exacerbations, hospitalizations, lung function, respiratory symptoms, GER severity, and adverse effects/complications. Results: For antacidmedication,when two studieswere aggregated, therewas no statistically significant effect on disease progression, defined as a 10% ormore decline in FVC,more than 50-mdecline in 6-minute walking distance, or death (risk ratio [RR], 0.88; 95% confidence interval [CI], 0.76-1.03).Aseparate study that could not be included in themetaanalysis found no statistically significant effect on disease progression when defined as a 5% ormore decline in FVC or death (RR, 1.10; 95% CI, 1.00-1.21) and an increase in disease progressionwhen defined as a 10% ormore decline in FVC or death (RR, 1.28; 95% CI, 1.08-1.51). For antireflux surgery, therewas also no statistically significant effect on disease progression (RR, 0.29; 95% CI, 0.06-1.26).Neither antacid medications nor antireflux surgerywas associated with improvements in the other outcomes. Conclusions: There is insufficient evidence to conclude that antacid medication or antireflux surgery improves respiratory outcomes in patientswith IPF,most ofwhomhad not had abnormalGER confirmed. Well-designed and adequately powered prospective studieswith objective evaluation forGER are critical to elucidate the role of antacidmedication and antireflux surgery for respiratory outcomes in patientswith IPF

Home oxygen therapy for adults with chronic lung disease an official american thoracic society clinical practice guideline

Background: Evidence-based guidelines are needed for effective delivery of home oxygen therapy to appropriate patients with chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD). Methods: The multidisciplinary panel created six research questions using a modified Delphi approach. A systematic review of the literature was completed, and the Grading of Recommendations Assessment, Development and Evaluation approach was used to formulate clinical recommendations. Recommendations: The panel found varying quality and availability of evidence and made the following judgments: 1) strong recommendations for long-term oxygen use in patients with COPD (moderate-quality evidence) or ILD (low-quality evidence) with severe chronic resting hypoxemia, 2) a conditional recommendation against long-term oxygen use in patients with COPD with moderate chronic resting hypoxemia, 3) conditional recommendations for ambulatory oxygen use in patients with COPD (moderate-quality evidence) or ILD (low-quality evidence) with severe exertional hypoxemia, 4) a conditional recommendation for ambulatory liquidoxygen use in patients who are mobile outside the home and require .3 L/min of continuous-flow oxygen during exertion (very-lowquality evidence), and 5) a recommendation that patients and their caregivers receive education on oxygen equipment and safety (bestpractice statement). Conclusions: These guidelines provide the basis for evidence-based use of home oxygen therapy in adults with COPD or ILD but also highlight the need for additional research to guide clinical practice

Global Health Impacts for Economic Models of Climate Change: A Systematic Review and Meta-Analysis.

Rationale: Avoiding excess health damages attributable to climate change is a primary motivator for policy interventions to reduce greenhouse gas emissions. However, the health benefits of climate mitigation, as included in the policy assessment process, have been estimated without much input from health experts. Objectives: In accordance with recommendations from the National Academies in a 2017 report on approaches to update the social cost of greenhouse gases (SC-GHG), an expert panel of 26 health researchers and climate economists gathered for a virtual technical workshop in May 2021 to conduct a systematic review and meta-analysis and recommend improvements to the estimation of health impacts in economic-climate models. Methods: Regionally resolved effect estimates of unit increases in temperature on net all-cause mortality risk were generated through random-effects pooling of studies identified through a systematic review. Results: Effect estimates and associated uncertainties varied by global region, but net increases in mortality risk associated with increased average annual temperatures (ranging from 0.1% to 1.1% per 1°C) were estimated for all global regions. Key recommendations for the development and utilization of health damage modules were provided by the expert panel and included the following: not relying on individual methodologies in estimating health damages; incorporating a broader range of cause-specific mortality impacts; improving the climate parameters available in economic models; accounting for socioeconomic trajectories and adaptation factors when estimating health damages; and carefully considering how air pollution impacts should be incorporated in economic-climate models. Conclusions: This work provides an example of how subject-matter experts can work alongside climate economists in making continued improvements to SC-GHG estimates

Global Health Impacts for Economic Models of Climate Change: A Systematic Review and Meta-Analysis

RATIONALE: Avoiding excess health damages attributable to climate change is a primary motivator for policy interventions to reduce greenhouse gas emissions. However, the health benefits of climate mitigation, as included in the policy assessment process, have been estimated without much input from health experts. OBJECTIVES: In accordance with recommendations from the National Academies in a 2017 report on approaches to update the social cost of greenhouse gases (SC-GHG), an expert panel of 26 health researchers and climate economists gathered for a virtual technical workshop in May 2021 to conduct a systematic review and meta-analysis and recommend improvements to the estimation of health impacts in economic-climate models. METHODS: Regionally-resolved effect estimates of unit increases in temperature on net all-cause mortality risk were generated through random-effects pooling of studies identified through a systematic review. RESULTS: Effect estimates, and associated uncertainties, varied by global region, but net increases in mortality risk associated with increased average annual temperatures (ranging from 0.1-1.1% per 1 degree C) was estimated for all global regions. Key recommendations for the development and utilization of health damage modules were provided by the expert panel, and include: not relying on individual methodologies in estimating health damages; incorporating a broader range of cause-specific mortality impacts; improving the climate parameters available in economic models; accounting for socio-economic trajectories and adaptation factors when estimating health damages; and carefully considering how air pollution impacts should be incorporated in economic-climate models. CONCLUSIONS: This work provides an example for how subject-matter experts can work alongside climate economists in making continued improvements to SC-GHG estimates

Idiopathic Pulmonary Fibrosis (an Update) and Progressive Pulmonary Fibrosis in Adults: An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline

Background: This American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociacion Latinoamericana de Torax guideline updates prior idiopathic pulmonary fibrosis (IPF) guidelines and addresses the progression of pulmonary fibrosis in patients with interstitial lung diseases (ILDs) other than IPF. Methods: A committee was composed of multidisciplinary experts in ILD, methodologists, and patient representatives. 1) Update of IPF: Radiological and histopathological criteria for IPF were updated by consensus. Questions about transbronchial lung cryobiopsy, genomic classifier testing, antacid medication, and antireflux surgery were informed by systematic reviews and answered with evidence-based recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. 2) Progressive pulmonary fibrosis (PPF): PPF was defined, and then radiological and physiological criteria for PPF were determined by consensus. Questions about pirfenidone and nintedanib were informed by systematic reviews and answered with evidence-based recommendations using the GRADE approach. Results: 1) Update of IPF: A conditional recommendation was made to regard transbronchial lung cryobiopsy as an acceptable alternative to surgical lung biopsy in centers with appropriate expertise. No recommendation was made for or against genomic classifier testing. Conditional recommendations were made against antacid medication and antireflux surgery for the treatment of IPF. 2) PPF: PPF was defined as at least two of three criteria (worsening symptoms, radiological progression, and physiological progression) occurring within the past year with no alternative explanation in a patient with an ILD other than IPF. A conditional recommendation was made for nintedanib, and additional research into pirfenidone was recommended. Conclusions: The conditional recommendations in this guideline are intended to provide the basis for rational, informed decisions by clinicians. © 2022 by the American Thoracic Societ

Idiopathic Pulmonary Fibrosis (an Update) and Progressive Pulmonary Fibrosis in Adults: An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline

Abstract Background: This American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociacion Latinoamericana de T orax guideline updates prior idiopathic pulmonary fibrosis (IPF) guidelines and addresses the progression of pulmonary fibrosis in patients with interstitial lung diseases (ILDs) other than IPF. Methods: A committee was composed of multidisciplinary experts in ILD, methodologists, and patient representatives. 1) Update of IPF: Radiological and histopathological criteria for IPF were updated by consensus. Questions about transbronchial lung cryobiopsy, genomic classifier testing, antacid medication, and antireflux surgery were informed by systematic reviews and answered with evidence-based recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. 2) Progressive pulmonary fibrosis (PPF): PPF was defined, and then radiological and physiological criteria for PPF were determined by consensus. Questions about pirfenidone and nintedanib were informed by systematic reviews and answered with evidence-based recommendations using the GRADE approach. Results: 1) Update of IPF: A conditional recommendation was made to regard transbronchial lung cryobiopsy as an acceptable alternative to surgical lung biopsy in centers with appropriate expertise. No recommendation was made for or against genomic classifier testing. Conditional recommendations were made against antacid medication and antireflux surgery for the treatment of IPF. 2) PPF: PPF was defined as at least two of three criteria (worsening symptoms, radiological progression, and physiological progression) occurring within the past year with no alternative explanation in a patient with an ILD other than IPF. A conditional recommendation was made for nintedanib, and additional research into pirfenidone was recommended. Conclusions: The conditional recommendations in this guideline are intended to provide the basis for rational, informed decisions by clinicians. Keywords: idiopathic pulmonary fibrosis; progressive pulmonary fibrosis; radiology; histopatholog

Meaningful Endpoints for Idiopathic Pulmonary Fibrosis (IPF) Clinical Trials:Emphasis on 'Feels, Functions, Survives'. Report of a Collaborative Discussion in a Symposium with Direct Engagement from Representatives of Patients, Investigators, the National Institutes of Health, a Patient Advocacy Organization, and a Regulatory Agency

Background: Idiopathic pulmonary fibrosis (IPF) carries significant mortality and unpredictable progression, with limited therapeutic options. Designing trials with patient-meaningful endpoints, enhancing the reliability and interpretability of results, and streamlining the regulatory approval process are of critical importance to advancing clinical care in IPF. Methods: A landmark in-person symposium in June 2023 assembled 43 participants from the US and internationally, including patients with IPF, investigators, and regulatory representatives, to discuss the immediate future of IPF clinical trial endpoints. Patient advocates were central to discussions, which evaluated endpoints according to regulatory standards and the FDA's 'feels, functions, survives' criteria. Results: Three themes emerged: 1) consensus on endpoints mirroring the lived experiences of patients with IPF; 2) consideration of replacing forced vital capacity (FVC) as the primary endpoint, potentially by composite endpoints that include 'feels, functions, survives' measures or FVC as components; 3) support for simplified, user-friendly patient-reported outcomes (PROs) as either components of primary composite endpoints or key secondary endpoints, supplemented by functional tests as secondary endpoints and novel biomarkers as supportive measures (FDA Guidance for Industry (Multiple Endpoints in Clinical Trials) available at: https://www.fda.gov/media/162416/download). Conclusions: This report, detailing the proceedings of this pivotal symposium, suggests a potential turning point in designing future IPF clinical trials more attuned to outcomes meaningful to patients, and documents the collective agreement across multidisciplinary stakeholders on the importance of anchoring IPF trial endpoints on real patient experiences-namely, how they feel, function, and survive. There is considerable optimism that clinical care in IPF will progress through trials focused on patient-centric insights, ultimately guiding transformative treatment strategies to enhance patients' quality of life and survival.</p

Meaningful Endpoints for Idiopathic Pulmonary Fibrosis (IPF) Clinical Trials:Emphasis on 'Feels, Functions, Survives'. Report of a Collaborative Discussion in a Symposium with Direct Engagement from Representatives of Patients, Investigators, the National Institutes of Health, a Patient Advocacy Organization, and a Regulatory Agency

Background: Idiopathic pulmonary fibrosis (IPF) carries significant mortality and unpredictable progression, with limited therapeutic options. Designing trials with patient-meaningful endpoints, enhancing the reliability and interpretability of results, and streamlining the regulatory approval process are of critical importance to advancing clinical care in IPF. Methods: A landmark in-person symposium in June 2023 assembled 43 participants from the US and internationally, including patients with IPF, investigators, and regulatory representatives, to discuss the immediate future of IPF clinical trial endpoints. Patient advocates were central to discussions, which evaluated endpoints according to regulatory standards and the FDA's 'feels, functions, survives' criteria. Results: Three themes emerged: 1) consensus on endpoints mirroring the lived experiences of patients with IPF; 2) consideration of replacing forced vital capacity (FVC) as the primary endpoint, potentially by composite endpoints that include 'feels, functions, survives' measures or FVC as components; 3) support for simplified, user-friendly patient-reported outcomes (PROs) as either components of primary composite endpoints or key secondary endpoints, supplemented by functional tests as secondary endpoints and novel biomarkers as supportive measures (FDA Guidance for Industry (Multiple Endpoints in Clinical Trials) available at: https://www.fda.gov/media/162416/download). Conclusions: This report, detailing the proceedings of this pivotal symposium, suggests a potential turning point in designing future IPF clinical trials more attuned to outcomes meaningful to patients, and documents the collective agreement across multidisciplinary stakeholders on the importance of anchoring IPF trial endpoints on real patient experiences-namely, how they feel, function, and survive. There is considerable optimism that clinical care in IPF will progress through trials focused on patient-centric insights, ultimately guiding transformative treatment strategies to enhance patients' quality of life and survival.</p