Pulmonary Disease Research Articles

Recent and anticipated novel drug approvals (Q2 2024 through Q1 2025).

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Health-system pharmacists play a crucial role in monitoring the pharmaceutical pipeline to manage formularies, allocate resources, and optimize clinical programs for new therapies. This article aims to support pharmacists by providing periodic updates on new and anticipated novel drug approvals. Selected drug approvals anticipated in the 12-month period covering the second quarter of 2024 through the first quarter of 2025 are reviewed. The analysis emphasizes drugs expected to have significant clinical and financial impact in hospitals and clinics, as selected from 52 novel drugs awaiting US Food and Drug Administration approval. New cellular and gene therapies for cancers continued to strengthen the pipeline, in addition to new drugs targeting previously untreatable conditions. Several novel drugs are being developed for rare and ultra-rare diseases such as hemophilia, Niemann-Pick disease type C, hereditary angioedema, and aromatic L-amino acid decarboxylase deficiency. The current drug pipeline includes new drugs with various indications for cancers and rare diseases as well as diabetes, acute coronary syndrome, chronic skin disorder, and chronic obstructive pulmonary disease.

Lung volume reduction surgery: a micro-costing analysis from a national tertiary referral Centre.

Lung volume reduction surgery (LVRS) is a clinically effective palliation procedure for patients with chronic obstructive pulmonary disease (COPD). LVRS has recently been commissioned by the NHS England. In this study, a costing model was developed to analyse cost and resource implications of different LVRS procedures. Three pathways were defined by their surgical procedures: bronchoscopic endobronchial valve insertion (EBV-LVRS), video assisted (VATS-LVRS), and robotic assisted LVRS (RATS-LVRS). The costing model considered use of hospital resources from the LVRS decision until 90-days after hospital admission. The model was calibrated with data obtained from an observational study, electronic health records, and expert opinion. Unit costs were obtained from the hospital finance department and reported in 2021-Euros. VATS-LVRS was associated with the lowest cost at €12,896 per patient. This compares to the costs of EBV-LVRS at €15,598 per patient and €13,305 per patient for RATS-LVRS. A large component of EBV-LVRS costs were accrued secondary to complications, including revision EBV-LVRS. This study presents a comprehensive model framework for the analysis of hospital-related resource use and costs for the three surgical modalities. In the future, service commissioning agencies, hospital management, and clinicians can use this framework to determine their modifiable resource use (composition of surgical teams, use of staff and consumables, planned length of stay, and revision rates for EBV-LVRS) and to assess the potential cost implications of changes in these parameters.

Long non-coding RNA Small Nucleolar RNA Host Gene 4 ameliorates cigarette smoke-induced proliferation, apoptosis, inflammation, and airway remodeling in alveolar epithelial cells through the modulation of the mitogen-activated protein kinase signaling pathway via the microRNA-409-3p/Four and a Half LIM Domains 1 axis

The long non-coding RNA (lncRNA) Small Nucleolar RNA Host Gene 4 (SNHG4) has been demonstrated to be significantly downregulated in various inflammatory conditions, yet its role in chronic obstructive pulmonary disease (COPD) remains elusive. This study aims to elucidate the biological function of SNHG4 in COPD and to unveil its potential molecular targets. Our findings reveal that both SNHG4 and Four and a Half LIM Domains 1 (FHL1) were markedly downregulated in COPD, whereas microRNA-409-3p (miR-409-3p) was upregulated. Importantly, SNHG4 exhibited a negative correlation with inflammatory markers in patients with COPD, but a positive correlation with forced expiratory volume in 1s percentage (FEV1%). SNHG4 distinguished COPD patients from non-smokers with high sensitivity, specificity, and accuracy. Overexpression of SNHG4 ameliorated cigarette smoke extract (CSE)-mediated inflammation, apoptosis, oxidative stress, and airway remodeling in 16HBE bronchial epithelial cells. These beneficial effects of SNHG4 overexpression were reversed by the overexpression of miR-409-3p or the silencing of FHL1. Mechanistically, SNHG4 competitively bound to miR-409-3p, mediating the expression of FHL1, and consequently improving inflammation, apoptosis, oxidative stress, and airway remodeling in 16HBE cells. Additionally, SNHG4 regulated the miR-409-3p/FHL1 axis to inhibit the activation of the mitogen-activated protein kinase (MAPK) pathway induced by CSE. In a murine model of COPD, knockdown of SNHG4 exacerbated CSE-induced pulmonary inflammation, apoptosis, and oxidative stress. In summary, our data affirm that SNHG4 mitigates pulmonary inflammation, apoptosis, and oxidative damage mediated by COPD through the regulation of the miR-409-3p/FHL1 axis.Graphical

Host tracheal and intestinal microbiomes inhibit Coccidioides growth in vitro.

Coccidioidomycosis is caused by a fungal pathogen that invades the host lungs, causing respiratory distress. In 2019, 20,003 cases of Valley fever were reported to the CDC. However, this number likely vastly underrepresents the true number of Valley fever cases, as many go undetected due to poor testing strategies and a lack of diagnostic models. Valley fever is also often misdiagnosed as bacterial pneumonia, resulting in 60%-80% of patients being treated with antibiotics prior to an accurate diagnosis. Misdiagnosis contributes to a growing problem of antibiotic resistance and antibiotic-induced microbiome dysbiosis; the implications for disease outcomes are currently unknown. About 5%-10% of symptomatic Valley fever patients develop chronic pulmonary disease. Valley fever causes a significant financial burden and a reduced quality of life. Little is known regarding what factors contribute to the development of chronic infections and treatments for the disease are limited.

Exhaled Breath Analysis for The Discrimination of Asthma and Chronic Obstructive Pulmonary Disease.

Abstract
BACKGROUND Chronic obstructive pulmonary disease (COPD) and asthma are the most common chronic respiratory diseases. In middle-aged and elderly patients, it is difficult to distinguish between COPD and asthma based on clinical symptoms and pulmonary function examinations in clinical practice. Thus, an accurate and reliable inspection method is required.
METHOD In this study, we aimed to identify breath biomarkers and evaluate the accuracy of breathomics-based methods for discriminating between COPD and asthma. In this multi-center cross-sectional study, exhaled breath samples were collected from 89 patients with COPD and 73 with asthma and detected on a high-pressure photon ionization time-of-flight mass spectrometry (HPPI-TOFMS) platform from October 20, 2022, to May 20, 2023, in four hospitals. Data analysis was performed from June 15, 2023, to August 16, 2023. The sensitivity, specificity, and accuracy were calculated to assess the overall performance of the VOC-based COPD and asthma discrimination models. Potential VOC markers related to COPD and asthma were also analyzed. 
RESULTS The age of all participants ranged from to 18-86 years, and 54 (33.3%) were men. Based on breathomics feature selection, ten VOCs were identified as COPD and asthma discrimination biomarkers via breath testing. The joint panel of these ten VOCs achieved an area under the curve (AUC) of 0.843, sensitivity of 75.9%, specificity of 87.5%, and accuracy of 80.0% in COPD and asthma discrimination. Furthermore, the VOCs detected in the breath samples were closely related to the clinical characteristics of COPD and asthma.
CONCLUSIONS The VOC-based COPD and asthma discrimination model showed good accuracy, providing a new strategy for clinical diagnosis. Breathomics-based methods may play an important role in the diagnosis of COPD and asthma.

Chronic Obstructive Pulmonary Disease Exacerbations Increase the Risk of Subsequent Cardiovascular Events: A Longitudinal Analysis of the COPDGene Study.

Cardiovascular disease (CVD) is the most important comorbidity in patients with chronic obstructive pulmonary disease (COPD). COPD exacerbations not only contribute to COPD progression but may also elevate the risk of CVD. This study aimed to determine whether COPD exacerbations increase the risk of subsequent CVD events using up to 15 years of prospective longitudinal follow-up data from the COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease) study. The COPDGene study is a large, multicenter, longitudinal investigation of COPD, including subjects at enrollment aged 45 to 80 years with a minimum of 10 pack-years of smoking history. Cox proportional hazards models and Kaplan-Meier survival curves were used to assess the risk of a composite end point of CVD based on the COPD exacerbation rate. Frequent exacerbators exhibited a higher cumulative incidence of composite CVD end points than infrequent exacerbators, irrespective of the presence of CVD at baseline. After adjusting for covariates, frequent exacerbators still maintained higher hazard ratios (HRs) than the infrequent exacerbator group (without CVD: HR, 1.81 [95% CI, 1.47-2.22]; with CVD: HR, 1.92 [95% CI, 1.51-2.44]). This observation remained consistently significant in moderate to severe COPD subjects and the preserved ratio impaired spirometry population. In the mild COPD population, frequent exacerbators showed a trend toward more CVD events. COPD exacerbations are associated with an increased risk of subsequent cardiovascular events in subjects with and without preexisting CVD. Patients with COPD experiencing frequent exacerbations may necessitate careful monitoring and additional management for subsequent potential CVD. URL: https://www.clinicaltrials.gov; Unique identifier: NCT00608764.

Lung Ultrasonography Accuracy for Diagnosis of Adult Pneumonia: Systematic Review and Meta-Analysis.

Pneumonia is a ubiquitous health condition with severe outcomes. The advancement of ultrasonography techniques allows its application in evaluating pulmonary diseases, providing safer and accessible bedside therapeutic decisions compared to chest X-ray and chest computed tomography (CT) scan. Because of its aforementioned benefits, we aimed to confirm the diagnostic accuracy of lung ultrasound (LUS) for pneumonia in adults. A systematic literature search was performed of Medline, Cochrane and Crossref, independently by two authors. The selection of studies proceeded based on specific inclusion and exclusion criteria without restrictions to particular study designs, language or publication dates and was followed by data extraction. The gold standard reference in the included studies was chest X-ray/CT scan or both. Twenty-nine (29) studies containing 6702 participants were included in our meta-analysis. Pooled sensitivity, specificity and PPV were 92% (95% CI: 91-93%), 94% (95% CI: 94 to 95%) and 93% (95% CI: 89 to 96%), respectively. Pooled positive and negative likelihood ratios were 16 (95% CI: 14 to 19) and 0.08 (95% CI: 0.07 to 0.09). The area under the ROC curve of LUS was 0. 9712. LUS has high diagnostic accuracy in adult pneumonia. Its contribution could form an optimistic clue in future updates considering this condition.

Exploring Clinical Remission in Moderate Asthma - Perspectives from Asia, the Middle East, and South America.

Clinical remission is a relatively new concept in asthma but recent research initiatives suggest it could be an ambitious and achievable therapeutic target for patients with asthma. In this modified Delphi study (comprising two online surveys, completed either side of a virtual scientific workshop), the opinions of a panel of respiratory physicians were evaluated to summarize perspective statements on key therapeutic outcomes and criteria for on-treatment clinical remission in patients with moderate asthma. An agreement threshold was pre-defined as agreement by ≥ 75% of participants. Surveys 1 and 2 were completed by 20 and 18 participants, respectively. Most participants (95%) agreed with the concept of clinical remission in moderate asthma and that this should be a desirable treatment goal (90%). Based on a composite measure of 4-6 desirable therapeutic outcomes, current understanding of clinical remission was considered as 12months with no exacerbations, no oral corticosteroids, no daytime or night-time asthma symptoms (Asthma Control Test score ≥ 20 or Asthma Control Questionnaire score ≤ 0.75), stable lung function, and no treatment-related adverse events. No agreement was reached on the role of relievers in defining therapeutic outcomes or on the wider use of biomarkers and airway hyperresponsiveness for defining asthma remission in clinical practice. In line with recent consensus statements from the United States and Europe, there was a high level of agreement on the elements of clinical remission among a panel of respiratory physicians from Asia, the Middle East, and South America. Extension of the concept of clinical remission to patients with moderate asthma was considered aligned with the potential of clinical remission as a goal of therapy.

The management pattern and outcomes of chronic thromboembolic pulmonary hypertension: rationale and design for a Chinese real-world study

BackgroundChronic thromboembolic pulmonary hypertension (CTEPH) is a progressive pulmonary vascular disorder with substantial morbidity and mortality, also a disease underdiagnosed and undertreated. It is potentially curable by pulmonary endarterectomy (PEA) in patients with surgically accessible thrombi. Balloon pulmonary angioplasty (BPA) and targeted medical therapy are options for patients with distal lesions or persistent/recurrent pulmonary hypertension after PEA. There is an urgent need to increase the awareness of CTEPH. Qualified CTEPH centers are still quite limited. Baseline characteristics, management pattern and clinical outcome of CTEPH in China needs to be reported.Methods and designThe CHinese reAl-world study to iNvestigate the manaGEment pattern and outcomes of chronic thromboembolic pulmonary hypertension (CHANGE) study is designed to provide the multimodality treatment pattern and clinical outcomes of CTEPH in China. Consecutive patients who are ≥ 14 year-old and diagnosed with CTEPH are enrolled. The diagnosis of CTEPH is confirmed in right heart catheterization and imaging examinations. The multimodality therapeutic strategy, which consists of PEA, BPA and targeted medical therapy, is made by a multidisciplinary team. The blood sample and tissue from PEA are stored in the central biobank for further research. The patients receive regular follow-up every 3 or 6 months for at least 3 years. The primary outcomes include all-cause mortality and changes in functional and hemodynamic parameters from baseline. The secondary outcomes include the proportion of patients experiencing lung transplantation, the proportion of patients experiencing heart and lung transplantation, and changes in health-related quality of life. Up to 31 December 2023, the study has enrolled 1500 eligible patients from 18 expert centers.ConclusionsAs a real-world study, the CHANGE study is expected to increase our understanding of CTEPH, and to fill the gap between guidelines and the clinical practice in the diagnosis, assessment and treatment of patients with CTEPH.Registration Number in ClinicalTrials.govNCT05311072.

Does an Immigrant Health Advantage Exist Among US Whites? Evidence from a Nationally-Representative Examination of Mental and Physical Well-Being.

This study examines whether an immigrant health advantage exists among US Whites, a group often used as a reference category in research on racial and ethnic health disparities. Using recent data from the National Health Interview Survey (2019-2022), I disaggregate non-Hispanic White adults (n = 41,752) by nativity status and use logistic regression models to assess differences in six measures of mental and physical health. The analysis includes self-reported conditions (depression, anxiety, fair/poor self-rated health) and diagnosed conditions that require interaction with the healthcare system (hypertension, diabetes, and chronic obstructive pulmonary disease, COPD). Foreign-born Whites have a significantly lower prevalence of each health outcome relative to US-born Whites. The immigrant health advantage remains significant for depression, anxiety, fair/poor health (i.e., self-reported conditions) and diagnosed hypertension, after adjusting for sociodemographic and healthcare characteristics. In contrast, the inclusion of these explanatory factors reduces the nativity gap in diagnosed diabetes and COPD to non-significance. Overall, the results indicate important variation in health among Whites that is missed in studies that focus on US-born Whites, alone. Scholars must continue to monitor the health of White immigrants, who are projected to grow to 20% of the US immigrant population in the years to come.

Perspective of Pneumonia in the Health-Care Setting

Pneumonia is a major worldwide health issue, impacting millions of individuals annually and leading to a significant number of hospitalizations and fatalities. Pneumonia is the leading infectious cause of mortality in children globally, responsible for almost 15% of all fatalities in children under 5 years old, as stated by the World Health Organization (WHO). Pneumonia is a prominent reason for hospitalization in the United States, resulting in around 1.5 million hospital admissions annually. Pneumonia is most prevalent in the elderly population, especially those who are 65 years old and above, and persons with preexisting medical disorders such as chronic obstructive pulmonary disease (COPD), heart disease, diabetes, or a compromised immune system. Pneumonia can vary in severity, ranging from a minor case that can be managed at home to a severe and life-threatening infection that necessitates hospitalization and intense medical care. The symptoms and severity of pneumonia might vary based on the underlying cause, the individual's age and overall health status, and other factors. Pneumonia is a severe respiratory infection that can be caused by several pathogens, such as bacteria, viruses, fungi, and unusual microorganisms. It is defined by the presence of inflammation in the alveoli, which are the small air sacs in the lungs responsible for gas exchange. This inflammation can result in the buildup of fluid or pus, which can hinder the lungs' functionality and impede the body's capacity to obtain sufficient oxygen. The significant burden of pneumonia globally, especially on vulnerable populations like children and the elderly, underscores the need for improved prevention, early detection, and effective treatment strategies. The range in severity highlights the importance of timely and appropriate medical care, as well as the need for patient education on recognizing and seeking treatment for pneumonia. Understanding the diverse etiologies and risk factors for pneumonia can inform the development of targeted interventions and public health measures to reduce the impact of this major respiratory illness.

Eosinophils and chronic obstructive pulmonary diseases (COPD) in hospitalized COVID-19 patients

BackgroundThe emergence of coronavirus disease 2019 (COVID-19) as a global health emergency necessitates continued investigation of the disease progression. This study investigated the relationship between eosinophilia and the severity of COVID-19 in chronic obstructive pulmonary disease (COPD) patients.MethodsThis cross-sectional study was conducted on 73 COPD patients infected by COVID-19 in Afzalipour Hospital, Iran. Peripheral blood samples were collected for hematological parameter testing, including eosinophil percentage, using Giemsa staining. Eosinophilia was defined as≥ 2% and non-eosinophilia as< 2%. The severity of pulmonary involvement was determined based on chest CT severity score (CT-SS) (based on the degree of involvement of the lung lobes, 0%: 0 points, 1–25%: 1 point, 26–50%: 2 points, 51–75%: 3 points, and 76–100%: 4 points). The CT-SS was the sum of the scores of the five lobes (range 0–20).ResultsThe average age of patients was 67.90±13.71 years, and most were male (54.8%). Non-eosinophilic COPD patients were associated with more severe COVID-19 (P= 0.01) and lower oxygen saturation (P= 0.001). In addition, the study revealed a significant difference in the chest CT severity score (CT-SS) between non-eosinophilic (9.76±0.7) and eosinophilic COPD patients (6.26±0.63) (P< 0.001). Although non-eosinophilic COPD patients had a higher mortality rate, this difference was not statistically significant (P= 0.16).ConclusionsOur study demonstrated that reduced peripheral blood eosinophil levels in COPD patients with COVID-19 correlate with unfavorable outcomes. Understanding this association can help us identify high-risk COPD patients and take appropriate management strategies to improve their prognosis.

Analysis of the direct economic impact of smoking-related hospitalizations in Italy.

Tobacco-related diseases have a substantial economic impact in terms of medical expenses, loss of productivity, and premature death. Tobacco use is estimated to be responsible for more than 90000 deaths each year in Italy. We aimed to evaluate the annual direct economic impact on the National Health System of hospitalizations attributable to tobacco smoking in Italy. We analyzed data from all the hospitalizations of patients aged ≥30 years that occurred in Italy for 12 selected tobacco-related diseases, during 2018. These diseases included oropharyngeal cancer, esophageal cancer, gastric cancer, lung cancer, pancreatic cancer, bladder cancer, laryngeal cancer, ischemic heart disease, stroke, diseases of arteries, arterioles, and capillaries, pneumonia and influenza, and chronic obstructive pulmonary disease. We obtained information on 984322 hospital discharge records, including each hospitalization's direct costs. Using relative risk estimates from the scientific literature, we computed the population attributable fraction for various tobacco-related diseases to estimate the economic impact attributable to tobacco smoking. One-third of all hospitalizations occurred in 2018 in Italy among people aged ≥30 years for 12 tobacco-related diseases were found to be attributable to smoking, accounting for a total cost of €1.64 billion. Among the diseases considered, those with the highest expenditures attributable to tobacco smoking were ischemic heart disease, cerebrovascular disease, and lung cancer, accounting for €556 million, €290 million, and €229 million, respectively. Tobacco has a substantial economic impact in Italy, accounting for around 6% of the total cost of hospitalizations in 2018. This figure is expected to be largely underestimated due to several conservative assumptions adopted in the statistical analyses. It is imperative to prioritize comprehensive tobacco control measures to counteract the huge healthcare costs due to tobacco smoking.

MSO-GP: 3-D segmentation of large and complex conjoined tree structures

Robust segmentation of large and complex conjoined tree structures in 3-D is a major challenge in computer vision. This is particularly true in computational biology, where we often encounter large data structures in size, but few in number, which poses a hard problem for learning algorithms. We show that merging multiscale opening with geodesic path propagation, can shed new light on this classic machine vision challenge, while circumventing the learning issue by developing an unsupervised visual geometry approach (digital topology/morphometry). The novelty of the proposed MSO-GP method comes from the geodesic path propagation being guided by a skeletonization of the conjoined structure that helps to achieve robust segmentation results in a particularly challenging task in this area, that of artery-vein separation from non-contrast pulmonary computed tomography angiograms. This is an important first step in measuring vascular geometry to then diagnose pulmonary diseases and to develop image-based phenotypes. We first present proof-of-concept results on synthetic data, and then verify the performance on pig lung and human lung data with less segmentation time and user intervention needs than those of the competing methods.

Atrial fibrillation inpatient management patterns and clinical outcomes during the conflict in Syria: An observational cohort study.

Atrial fibrillation (AF) is the most common sustained arrhythmia worldwide. However, there is no data on AF inpatient management strategies and clinical outcomes in Syria. The study aims were to review the inpatient management of patients with AF and assess cardiovascular (CV) mortality in a tertiary cardiology centre in Latakia, Syria. A single-centre retrospective observational cohort study was conducted at Tishreen's University Hospital, Latakia, Syria, from June 2021 to June 2023. Patients ≥16years of age presenting and being treated for AF as the primary diagnosis with or without a thromboembolic event were included. Medical records were examined for patients' demographics, laboratory results, treatment plans and inpatient details. Studied outcomes include inpatient all-cause and CV mortality, ischemic and bleeding events, and conversion to sinus rhythm (SR). The study included 596 patients. The median age was 58, and 61% were males. 121 patients (20.3%) were known to have AF. A rhythm control strategy was pursued in 39% of patients. Ischemic and bleeding events occurred in 62 (11%) and 12 (2%), respectively. CV and all-cause mortality occurred in 28 (4.7%) and 31 patients (5%), respectively. The presence of valvular heart disease (VHD) (adjusted odds ratio (aOR) = 9.1, 95% confidence interval (CI): 1.7 to 55.1, p < .001), thyroid disease (aOR: 9.7, 95% CI = 1.2 to 91.6, p < .001) and chronic obstructive pulmonary disease (COPD) (aOR: 82, 95% CI: 12.7 to 71, p < .001) were independent risk factors of increased CV inpatient mortality. Syrian inpatients admitted with AF in Latakia are relatively younger than those in other countries. Active thyroid disease, COPD and VHD were independent risk factors of inpatient CV mortality with AF.

Contemporary Concise Review 2023: Environmental and occupational lung diseases.

Air pollutants have various effects on human health in environmental and occupational settings. Air pollutants can be a risk factor for incidence, exacerbation/aggravation and death due to various lung diseases, including asthma, chronic obstructive pulmonary disease (COPD), hypersensitivity pneumonitis or pneumonia (HP), pulmonary fibrosis such as pneumoconiosis and malignant respiratory diseases such as lung cancer and malignant pleural mesothelioma. Environmental and occupational respiratory diseases are crucial clinical and social issues worldwide, although the burden of respiratory disease due to environmental and occupational causes varies depending on country/region, demographic variables, geographical location, industrial structure and socioeconomic situation. The correct recognition of environmental and occupational lung diseases and taking appropriate measures are essential to their effective prevention.

Chronic obstructive pulmonary disease (COPD): eosinophilia and novel drug therapies

The phenotyping of chronic obstructive pulmonary disease (COPD) has increasingly gained attention in recent years, as it leads to new and individualized therapeutic concepts. The aim is to provide an overview of the heterogeneity of COPD and to summarize current drug therapy concepts, particularly in the context of eosinophilic airway inflammation. Several prospective, randomized, placebo-controlled studies have shown areduction in exacerbations and overall mortality with inhaled triple therapy using an inhaled corticosteroid and dual bronchodilation. The higher the eosinophils in the blood, the greater the expected effect. In addition, areduction in exacerbations with biologics in COPD with eosinophilia has been demonstrated for dupilumab. Eosinophil-guided therapy for acute exacerbations is the subject of current research. For COPD without exacerbations, dual bronchodilation forms the basis of inhaled therapy. With exacerbations, inhaled triple therapy is indicated for patients with ablood eosinophil count of ≥ 300/µl. This type of treatment may also be useful when eosinophils are between 100 and 300/µl. Therapy with dupilumab is apossible option for the eosinophilic phenotype in the near future.

Development and validation of reference equations for dual-energy x-ray absorptiometry-derived measures of fat-free mass in adults aged 45-85 years: Results from the Canadian Longitudinal Study on Aging.

Reference equations for fat-free (FFM) and lean soft tissue mass (LM) measures obtained from dual-energy x-ray absorptiometry (DEXA) are important for the interpretation of body composition. This study developed and validated reference equations for FFM and LM using DEXA from the Canadian Longitudinal Study on Aging. Reference equations were developed using data from a random population-based sample of ostensibly healthy and functionally independent adults aged 45-85years. Reference equations for absolute (accounting for age, sex, height, and body mass) and height-adjusted (accounting for age, sex, and body mass index) measures of FFM and LM were developed using quantile regression. Reference equations were respectively developed and validated in derivation (80%) and validation cohorts (20%). Reference equations were applied to symptomatic adults with self-reported chronic obstructive pulmonary disease (COPD) or heart disease to assess discriminant validity; and compared with other published equations to assess performance. Bland-Altman analyses and Lin's concordance correlation coefficients were utilised to assess agreement. Reference equations for 5th, 10th, 50th, 90th, and 95th percentiles were developed for DEXA-derived estimates of FFM and LM based on 1,881 healthy participants (57%male) aged 55years [IQR: 50-61]. Reference equations performed comparably in the validation cohort and discriminated reference values between healthy adults and people with symptomatic COPD or heart disease. Previously published reference equations tended to over- or under-predict estimates of LM compared with the current reference equations. This study provides a comprehensive and validated set of reference equations for estimating and interpreting FFM and LM from DEXA in Canadian adults aged 45-85 years.

Longitudinal multicompartment characterization of host-microbiota interactions in patients with acute respiratory failure

Critical illness can significantly alter the composition and function of the human microbiome, but few studies have examined these changes over time. Here, we conduct a comprehensive analysis of the oral, lung, and gut microbiota in 479 mechanically ventilated patients (223 females, 256 males) with acute respiratory failure. We use advanced DNA sequencing technologies, including Illumina amplicon sequencing (utilizing 16S and ITS rRNA genes for bacteria and fungi, respectively, in all sample types) and Nanopore metagenomics for lung microbiota. Our results reveal a progressive dysbiosis in all three body compartments, characterized by a reduction in microbial diversity, a decrease in beneficial anaerobes, and an increase in pathogens. We find that clinical factors, such as chronic obstructive pulmonary disease, immunosuppression, and antibiotic exposure, are associated with specific patterns of dysbiosis. Interestingly, unsupervised clustering of lung microbiota diversity and composition by 16S independently predicted survival and performed better than traditional clinical and host-response predictors. These observations are validated in two separate cohorts of COVID-19 patients, highlighting the potential of lung microbiota as valuable prognostic biomarkers in critical care. Understanding these microbiome changes during critical illness points to new opportunities for microbiota-targeted precision medicine interventions.

Clinician Views of Proactive Tobacco Treatment Programs: A Qualitative Evaluation.

Proactive tobacco treatment programs are an evidence-based strategy to recruit patients who smoke to make supported quit attempts. However, such programs are rarely implemented. We performed a qualitative assessment of clinicians to inform the creation of a proactive outreach program for patients with chronic obstructive pulmonary disease (COPD) who smoke. Informed by the Consolidated Framework for Implementation Research, we conducted semi-structured interviews to assess clinician views of proactive outreach, including barriers, program structure, and the use of technology. Clinicians included primary and specialty care physicians, nurses and advanced practice providers, pharmacists, respiratory therapists, a psychologist, and relevant members of leadership. Interviews were transcribed and analyzed using directed content analysis. Clinicians in all roles identified that proactive outreach could be an effective use of resources to help patients with COPD who smoke quit with several advantages over the current state. Clinicians disagreed on the priority population (e.g., younger patients, sicker patients), and to some extent on whether proactive outreach is a clinical priority. Though they supported that technology could be part of the outreach program, most advocated for multiple avenues (phone calls, drop-in clinic, texting), as these patients were perceived to be low technology utilizers. The primary implementation barriers were competing priorities and cost, as well as unclear billing and staffing models. Clinicians support proactive outreach for patients with COPD, but the optimal way to structure, staff, and fund such programs remains unclear. Health systems should leverage implementation strategies to speed uptake of these potentially life-saving programs.