Treatment of Systemic Sclerosis-associated Interstitial Lung Disease: Evidence-based Recommendations. An Official American Thoracic Society Clinical Practice Guideline.

Background: Interstitial lung disease (ILD) is a significant cause of morbidity and mortality in patients with systemic sclerosis (SSc). To date, clinical practice guidelines regarding treatment for patients with SSc-ILD are primarily consensus based. Methods: An international expert guideline committee composed of 24 individuals with expertise in rheumatology, SSc, pulmonology, ILD, or methodology, and with personal experience with SSc-ILD, discussed systematic reviews of the published evidence assessed using the Grading of Recommendations, Assessment, Development, and Evaluation approach. Predetermined conflict-of-interest management strategies were applied, and recommendations were made for or against specific treatment interventions exclusively by the nonconflicted panelists. The confidence in effect estimates, importance of outcomes studied, balance of desirable and undesirable consequences of treatment, cost, feasibility, acceptability of the intervention, and implications for health equity were all considered in making the recommendations. This was in accordance with the American Thoracic Society guideline development process, which is in compliance with the Institute of Medicine standards for trustworthy guidelines. Results: For treatment of patients with SSc-ILD, the committee: 1) recommends the use of mycophenolate; 2) recommends further research into the safety and efficacy of (a) pirfenidone and (b) the combination of pirfenidone plus mycophenolate; and 3) suggests the use of (a) cyclophosphamide, (b) rituximab, (c) tocilizumab, (d) nintedanib, and (e) the combination of nintedanib plus mycophenolate. Conclusions: The recommendations herein provide an evidence-based clinical practice guideline for the treatment of patients with SSc-ILD and are intended to serve as the basis for informed and shared decision making by clinicians and patients.

Trends in Lung Cancer Incidence and Mortality (1990-2019) in the United States: A Comprehensive Analysis of Gender and State-Level Disparities.

PURPOSE: Lung cancer is the leading cause of cancer-related deaths in the United States. This study aims to analyze lung cancer incidence, mortality, and related statistics from 1990 to 2019, focusing on national- and state-level trends and exploring potential disparities between sexes. METHODS: The Global Burden of Disease database was used to extract tracheal, bronchus, and lung cancer mortality data from 1990 to 2019 for both males and females and across all states of the United States. Age-standardized incidence rates, age-standardized mortality rates, disability-adjusted life years (DALYs), and mortality-to-incidence indices (MIIs) were studied to assess for gender-based, geographic, and temporal disparities. Joinpoint regression analysis was performed to further evaluate trends. RESULTS: The incidence of these cancers in the United States decreased between 1990 and 2019 by 23.35%, with a more significant decline in males (37.73%) than females (1.41%). Similarly, for mortality, a decrease was observed for both sexes combined (26.83%), but much more significantly for males (40.23%) than females (6.01%). The MIIs decreased overall, but there were variations across states. DALYs decreased for both sexes combined, with males experiencing a larger reduction, but an increase was noted in some states for females. CONCLUSION: This analysis reveals diverse trends pertaining to the incidence, mortality, and disability burden associated with lung cancer by sex and states in the United States, emphasizing the need for targeted interventions to reduce disparities. These findings contribute to our understanding of the current landscape of lung cancer and can inform future strategies for prevention, early detection, and management.

Idiopathic pulmonary fibrosis: state of the art for 2023.

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease characterised by worsening respiratory symptoms and physiological impairment. Increasing awareness of the clinical manifestations of IPF, more widespread use of computed tomography scans and other potential factors have contributed to a rising prevalence of IPF over the last two decades, especially among people over the age of 65 years. Significant advances in the understanding of the pathobiology of IPF have emerged, and multiple genetic and nongenetic contributors have been identified. The individual patient course and the rate of disease progression in IPF are often unpredictable and heterogeneous. The rate of lung function decline is further modified by treatment with antifibrotic therapies, which have been shown to slow down disease progression. The presence of comorbid conditions may increase symptom burden and impact survival. Clinical monitoring at regular intervals to assess for disease progression by worsening symptoms, physiological parameters and/or radiological features is essential to assess the natural disease course and to guide further management, including prompt detection of complications and comorbid conditions that warrant additional treatment considerations, and timely consideration of referral to palliative care and lung transplantation for the appropriate patient. More studies are needed to determine whether early detection of IPF might improve patient outcomes. The purpose of this concise clinical review is to provide an update on IPF diagnosis, epidemiology, natural history and treatment in the context of new knowledge and latest clinical practice guidelines.

Care teams misunderstand what most upsets patients about their care.

BACKGROUND: Negative healthcare delivery experiences can cause lasting patient distress and medical service misuse and disuse. Yet no multi-site study has examined whether care-team members understand what most upsets patients about their care. METHODS: We interviewed 373 patients and 360 care-team members in the medical oncology and ambulatory surgery clinics of 11 major healthcare organizations across six U.S. census regions. Patients deeply upset by a service-related experience (n = 99, 27%) answered questions about that experience, while care-team members (n = 360) answered questions about their beliefs regarding what most upsets patients. We performed content analysis to identify memorably upsetting care (MUC) themes; a generalized estimating equation to explore whether MUC theme mention frequencies varied by participant role (care-team member vs. patient), specialty (oncology vs. surgery), facility (academic vs. community), and gender; and logistic regressions to investigate the effects of participant characteristics on individual themes. RESULTS: MUC themes included three systems issues (inefficiencies, access barriers, and facilities problems) and four care-team issues (miscommunication, neglect, coldness, and incompetence). MUC theme frequencies differed by role (all Ps < 0.001), with more patients mentioning care-team coldness (OR = 0.37; 95% CI, 0.23-0.60) and incompetence (OR = 0.17; 95% CI, 0.09-0.31); but more care-team members mentioning system inefficiencies (OR = 7.01; 95% CI, 4.31-11.40) and access barriers (OR, 5.48; 95% CI, 2.81-10.69). CONCLUSIONS: When considering which service experiences most upset patients, care-team members underestimate the impact of their own behaviors and overestimate the impact of systems issues. IMPLICATIONS: Healthcare systems should reconsider how they collect, interpret, disseminate, and respond to patient service reports. LEVEL OF EVIDENCE: Level III.

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 Asociación Latinoamericana de Tórax 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.

A rare etiology of pulmonary nodules.

INTRODUCTION: Pulmonary nodules are a frequent finding on chest imaging studies, with differential including multiple benign entities, but malignancy is often also a concern. Computed Tomography (CT) and Fluorodeoxyglucose (FDG)-Positron Emission Tomography (PET) scans have improved the characterization of pulmonary nodules. However, many nodules remain indeterminate and require periodic monitoring. Here we report two nodular pulmonary amyloidosis cases as a rare etiology of enlarging pulmonary nodules with FDG avidity. CASE PRESENTATION: Case 1: 75-year-old woman with a history of asthma, emphysema, bronchiectasis, and a 48 pack-year smoking history was found to have subcentimeter groundglass pulmonary nodules in the right lower lobe (RLL). Follow-up imaging demonstrated an increased solid component of a RLL bulla associated with mild FDG uptake on PET scan. A CT-guided biopsy revealed amyloid deposition. Case 2: 77-year-old man with a history of interstitial lung disease, asbestos exposure, prior tobacco use, and atrial fibrillation treated with amiodarone was found to have a 1.6cm RLL nodule. Follow-up imaging identified an interval increase to 2.0cm associated with moderate FDG uptake on PET scan. Transthoracic biopsy identified amyloid deposition. DISCUSSION: Nodular pulmonary amyloidosis is a rare form of amyloidosis which may present as an enlarging pulmonary nodule with FDG avidity, raising concern for malignancy. A CT-guided biopsy is a safe way to establish a diagnosis. Recent studies have demonstrated an association between nodular pulmonary amyloidosis and marginal zone lymphomas, which warrants longitudinal follow-up for evolution to lymphoproliferative disorder.

Qualitative coronary artery calcification scores and risk of all cause, COPD and pneumonia hospital admission in a large CT lung cancer screening cohort.

BACKGROUND: Patients at high-risk for lung cancer and qualified for CT lung cancer screening (CTLS) are at risk for numerous cardio-pulmonary comorbidities. We sought to examine if qualitatively assessed coronary artery calcifications (CAC) on CTLS exams could identify patients at increased risk for non-cardiovascular events such as all cause, COPD and pneumonia related hospitalization and to verify previously reported associations between CAC and mortality and cardiovascular events. STUDY DESIGN AND METHODS: Patients (n = 4673) from Lahey Hospital and Medical Center who underwent CTLS from January 12, 2012 through September 30, 2017 were included with clinical follow-up through September 30, 2019. CTLS exams were qualitatively scored for the presence and severity of CAC at the time of exam interpretation using a four point scale: none, mild, moderate, and marked. Multivariable Cox regression models were used to evaluate the association between CT qualitative CAC and all-cause, COPD-related, and pneumonia-related hospital admissions. RESULTS: 3631 (78%) of individuals undergoing CTLS had some degree of CAC on their baseline exam: 1308 (28.0%), 1128 (24.1%), and 1195 (25.6%) had mild, moderate and marked coronary calcification, respectively. Marked CAC was associated with all-cause hospital admission and pneumonia related admissions HR 1.48; 95% CI 1.23-1.78 and HR 2.19; 95% 1.30-3.71, respectively. Mild, moderate and marked CAC were associated with COPD-related admission HR 2.30; 95% CI 1.31-4.03, HR 2.17; 95% CI 1.20-3.91 and HR 2.27; 95% CI 1.24-4.15. CONCLUSION: Qualitative CAC on CTLS exams identifies individuals at elevated risk for all cause, pneumonia and COPD-related hospital admissions.

Proposed Quality Metrics for Lung Cancer Screening Programs: A National Lung Cancer Roundtable Project.

Lung cancer screening with a low radiation dose chest CT scan is the standard of care for screening-eligible individuals. The net benefit of screening may be optimized by delivering high-quality care, capable of maximizing the benefit and minimizing the harms of screening. Valid, feasible, and relevant indicators of the quality of lung cancer screening may help programs to evaluate their current practice and to develop quality improvement plans. The purpose of this project was to develop quality indicators related to the processes and outcomes of screening. Potential quality indicators were explored through surveys of multidisciplinary lung cancer screening experts. Those that achieved predefined measures of consensus for each of the validity, feasibility, and relevance domains are proposed as quality indicators. Each of the proposed indicators is described in detail, with guidance on how to define, measure, and improve program performance within the indicator.

Lung cancer mortality in Europe and the USA between 2000 and 2017: an observational analysis.

BACKGROUND: The lung is the most common site for cancer and has the highest worldwide cancer-related mortality. Our study reports and compares trends in lung cancer mortality in the USA and 26 European countries. STUDY DESIGN AND METHODS: Lung cancer mortality data were extracted for males and females for each of the years 2000-2017 from the World Health Organization (WHO) Mortality and the Centers for Disease Control and Prevention (CDC) WONDER databases. Lung cancer mortality trends were compared using Joinpoint regression analysis, and male-to-female mortality ratios were calculated. RESULTS: Down-trending lung cancer mortality rates were observed in males in all countries except Cyprus and Portugal between 2000 and 2017. In females, increasing mortality rates were observed in 22 of the 27 countries analysed. Latvia had the highest estimated annual percentage change (EAPC) in male mortality (-9.6%) between 2013 and 2015. In the USA, EAPCs were -5.1% for males and -4.2% for females between 2014 and 2017. All countries had an overall decrease in the ratio of male-to-female lung cancer mortality. The most recent observation of median male-to-female mortality was 2.26 (IQR 1.92-4.05). The countries with the greatest current sex disparity in lung cancer mortality were Lithuania (5.51) and Latvia (5.00). CONCLUSION: Between 2000 and 2017, lung cancer mortality rates were decreasing for males in Europe and the USA, whereas increasing lung cancer mortality rates were generally observed in females. There is a persistent but decreasing sex-mortality gap, with men having persistently greater lung cancer mortality but with rates decreasing faster than women.

Qualitative emphysema and risk of COPD hospitalization in a multicenter CT lung cancer screening cohort study.

BACKGROUND: In the United States, 9 to 10 million Americans are estimated to be eligible for computed tomographic lung cancer screening (CTLS). Those meeting criteria for CTLS are at high-risk for numerous cardio-pulmonary co-morbidities. The objective of this study was to determine the association between qualitative emphysema identified on screening CTs and risk for hospital admission. STUDY DESIGN AND METHODS: We conducted a retrospective multicenter study from two CTLS cohorts: Lahey Hospital and Medical Center (LHMC) CTLS program, Burlington, MA and Mount Auburn Hospital (MAH) CTLS program, Cambridge, MA. CTLS exams were qualitatively scored by radiologists at time of screening for presence of emphysema. Multivariable Cox regression models were used to evaluate the association between CT qualitative emphysema and all-cause, COPD-related, and pneumonia-related hospital admission. RESULTS: We included 4673 participants from the LHMC cohort and 915 from the MAH cohort. 57% and 51.9% of the LHMC and MAH cohorts had presence of CT emphysema, respectively. In the LHMC cohort, the presence of emphysema was associated with all-cause hospital admission (HR 1.15, CI 1.07-1.23; p < 0.001) and COPD-related admission (HR 1.64; 95% CI 1.14-2.36; p = 0.007), but not with pneumonia-related admission (HR 1.52; 95% CI 1.27-1.83; p < 0.001). In the MAH cohort, the presence of emphysema was only associated with COPD-related admission (HR 2.05; 95% CI 1.07-3.95; p = 0.031). CONCLUSION: Qualitative CT assessment of emphysema is associated with COPD-related hospital admission in a CTLS population. Identification of emphysema on CLTS exams may provide an opportunity for prevention and early intervention to reduce admission risk.