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Abstract Rationale Increased risk of coronavirus disease (COVID-19) hospitalization and death has been reported among patients with clinical lung disease. Objectives To test the association of objective measures of prepandemic lung function and structure with COVID-19 outcomes in U.S. adults. Methods Prepandemic obstruction (FEV1/FVC < 0.70) and restriction (FEV1/FVC ⩾ 0.7, FVC < 80%) were defined based on the most recent spirometry exam conducted in 11 prospective U.S. general population–based cohorts. Severe obstruction was classified by FEV1 < 50%. Percentage emphysema, percentage high-attenuation areas, and interstitial lung abnormalities were defined on computed tomography in a subset. Incident COVID-19 was ascertained via questionnaires, serosurvey, and medical records from 2020 to 2023 and classified as severe (hospitalized or fatal) or nonsevere. Cause-specific hazard models were adjusted for sociodemographics, anthropometry, smoking, comorbidities, and COVID-19 vaccination status. Measurements and Main Results Among 29,323 participants (mean age, 67 yr), there were 748 severe incident COVID-19 cases over median follow-up of 17.3 months from March 1, 2020. Greater hazards of severe COVID-19 were associated with severe obstruction (vs. normal; adjusted hazard ratio [aHR], 2.11; 95% confidence interval [CI], 1.02–1.27), restriction (vs. normal; aHR, 1.40; 95% CI, 1.12–1.76), and percentage emphysema (highest vs. lowest quartile; aHR, 1.64; 95% CI, 1.03–2.61), but not greater high-attenuation areas or interstitial lung abnormalities. COVID-19 vaccination provided greater absolute risk reduction in these groups. Results were similar in participants without smoking, obesity, or clinical cardiopulmonary disease. Conclusions Prepandemic severe spirometric obstruction, spirometric restriction, and greater percentage emphysema lung on computed tomography were associated with risk of severe COVID-19. These findings support enhanced COVID-19 risk mitigation for individuals with impaired lung health and warrant further mechanistic studies on interactions of lung function, structure, and vulnerability to acute respiratory illnesses.

ABSTRACT Background Hospital at home (HaH) provides hospital‐level care at home as a substitute for brick‐and‐mortar hospital care. Multiple HaH studies demonstrate HaH provides safe, high‐quality, cost‐effective care. However, practices have varied approaches to delivering care and no HaH‐specific national standards exist. We aimed to develop national practice standards for HaH and assess practice performance against the standards. Methods The HaH Users Group (HaHUG), the national convener of HaH practices, assembled the Practice Standards Council in 2019 to develop evidence‐based standards for HaH. We reviewed existing international standards and the requirements of the Centers for Medicare and Medicaid Services Acute Hospital Care at Home Waiver. We engaged in multiple iterative rounds to develop domains and standards within each domain and then held an open comment period. We distributed an online survey for all HaHUG practices to self‐assess whether they did not meet (score, −1), met (score, 0), or exceeded (score, +1) each standard. The American Hospital Association's Annual Survey was used to describe practices that did and did not complete the practice standards survey. Results Final practice standards included 31 standards in 7 domains: leadership; education and training; human resources management; quality and quality improvement; safe practice and environment; and clinical standards and protocols. The majority of HaH practices self‐rated that they met or exceeded standards: scores ranged from −5 to 31; mean score of 9.75 (SD, 12.60). Forty‐nine of 213 eligible HaH practices completed the survey (response rate, 23.0%). Most hospitals were large (65% > 299 beds), nonprofit (85%), teaching (90%) centers that cared for a large proportion of patients with Medicaid. Conclusion We present the first national practice standards for HaH. The vast majority of HaH practices met or exceeded these standards by their own assessment. There was a range of performance across standards, demonstrating strengths and opportunities for ongoing development and quality improvement.

ABSTRACT Although lung transplant recipients who develop Ureaplasma- associated hyperammonemia syndrome are treated with Ureaplasma -targeted antibiotics, optimal therapy is incompletely defined, and typically not based on real-time antimicrobial susceptibility testing results. This study compared levofloxacin, azithromycin, and doxycycline prevention and treatment of Ureaplasma urealyticum (UU) and Ureaplasma parvum (UP) infections in an immunosuppressed murine lung infection model. For prophylaxis, mice received antibiotics before infection with UP-FS (susceptible to all study antibiotics), UP-AzmR (azithromycin-resistant), UP-LevR (levofloxacin-resistant), or UU-DoxR (doxycycline-resistant), with lung bacterial loads (color changing units [CCUs]) measured 18 hours following infection. For UP-FS, doxycycline was most active (Δ4.84 log 10 CCU/g; P = 0.0006), followed by levofloxacin (Δ2.45 log 10 CCU/g; P = 0.018), with azithromycin yielding a nonsignificant CCU reduction. Doxycycline (Δ1.9 log 10 CCU/g; P = 0.0025) and levofloxacin (Δ1.3 log 10 CCU/g; P = 0.004) showed activity against UP-AzmR. Only doxycycline showed activity against UP-LevR (Δ2.28 log 10 CCU/g; P = 0.0002), and only azithromycin showed activity against UU-DoxR (Δ0.67 log 10 CCU/g; P = 0.0175). For treatment, antibiotics were administered 24 hours following infection; doxycycline significantly reduced bacterial loads of all study isolates, except UU-DoxR. In addition, azithromycin was active against UP-LevR (Δ1.21 log 10 CCU/g reduction; P = 0.0003). In summary, except for doxycycline-resistant UU, doxycycline was active in preventing and treating Ureaplasma lung infection in immunosuppressed mice.

Mitral regurgitation (MR) in lung transplant (LTx) recipients is a rare but complex cardiopulmonary phenomenon. The overlap between symptoms of MR and post-LTx complications, such as primary graft dysfunction, complicates its diagnosis and management. This systematic review aims to characterize the incidence, pathophysiology, presentation, and management of MR in LTx patients. We conducted a literature search in PubMed, Web of Science, Scopus, and Embase. The search yielded 133 studies, of which 11 were included. Data regarding MR development, clinical presentation, echocardiographic findings, and management strategies were extracted and analyzed. Perioperative MR, occurring during or immediately post-LTx, was frequently attributed to the systolic anterior motion of the mitral valve (MV) occurring in the setting of hypovolemia and/or inotrope usage. Later postoperative MR, on the other hand, was associated with reverse ventricular remodeling and mitral annular dilation, although some variability in the literature was present. Preexisting MR or ventricular dysfunction, elongated MV leaflets, and bilateral LTx procedure appeared to be risk factors for MR development. Management was dependent on the timing of MR and its pathophysiology, where systolic anterior motion–related MR was treated with medical therapy, whereas postoperative MR often required MV interventions. In conclusion, the diagnosis of MR in LTx patients is complicated by its symptomatic overlap with other post-LTx complications. Echocardiographic monitoring in patients with preexisting MR, regardless of severity, is essential for early identification and management. Further research is needed to better understand the underlying mechanisms and refine management strategies for MR in this population.

Abstract Rationale Stereotactic body radiation therapy (SBRT) represents an effective therapeutic strategy for early-stage non–small cell lung cancer (NSCLC); however, local and systemic recurrences represent ongoing challenges. Computed tomography (CT) radiomics-based risk models can potentially be used to predict the risk of local recurrence on pretreatment CT scans. Objective Development of a radiomics model to predict local recurrence after SBRT in patients with NSCLC. Methods This single-institution study includes a retrospective case-control training set (20 patients with local recurrence and 40 control subjects) and an independent validation set (198 consecutive cases) of patients with early-stage NSCLC treated with SBRT. Tumors were semiautomatically segmented, and 102 quantitative radiomic features, including texture, landscape, spatial, nodule shape, and nodule surface features, were extracted. These features were included in three separate multivariable models to predict the risk of recurrence on the basis of pre-SBRT, post-SBRT, and the difference between the pre-SBRT and post-SBRT scans (Delta model). The pre-SBRT model was subsequently validated in an independent validation set. Results Thirteen independent variables were selected for the models using the Boruta algorithm. The sensitivity, specificity, and area under the curve of the pre-SBRT, post-SBRT, and Delta models were 85%, 90%, and 0.91; 85%, 92.5%, and 0.92; and 85%, 92.5%, and 0.94, respectively. The pre-SBRT model was validated in the independent validation set (area under the curve, 0.89; confidence interval, 0.83–0.92), because this model was believed to be the most useful to assist in individualized treatment planning. Conclusions Radiomic analysis facilitated the development of three high-performing models predicting local recurrence using either pre-SBRT CT, post-SBRT CT, or the change between these two. We successfully validated the most clinically relevant model, the pre-SBRT model. Although this model needs further validation, it may facilitate individualized surveillance, treatment planning, and selection of adjuvant therapy.

ABSTRACTBackground and ObjectiveThe diagnosis of interstitial lung diseases (ILDs) often relies on the integration of various clinical, radiological, and histopathological data. Achieving high diagnostic accuracy in ILDs, particularly for distinguishing usual interstitial pneumonia (UIP), is challenging and requires a multidisciplinary approach. Therefore, this study aimed to develop a multimodal artificial intelligence (AI) algorithm that combines computed tomography (CT) and histopathological images to improve the accuracy and consistency of UIP diagnosis.MethodsA dataset of CT and pathological images from 324 patients with ILD between 2009 and 2021 was collected. The CT component of the model was trained to identify 28 different radiological features. The pathological counterpart was developed in our previous study. A total of 114 samples were selected and used for testing the multimodal AI model. The performance of the multimodal AI was assessed through comparisons with expert pathologists and general pathologists.ResultsThe developed multimodal AI demonstrated a substantial improvement in distinguishing UIP from non‐UIP, achieving an AUC of 0.92. When applied by general pathologists, the diagnostic agreement rate improved significantly, with a post‐model κ score of 0.737 compared to 0.273 pre‐model integration. Additionally, the diagnostic consensus rate with expert pulmonary pathologists increased from κ scores of 0.278–0.53 to 0.474–0.602 post‐model integration. The model also increased diagnostic confidence among general pathologists.ConclusionCombining CT and histopathological images, the multimodal AI algorithm enhances pathologists' diagnostic accuracy, consistency, and confidence in identifying UIP, even in cases where specialised expertise is limited. image

Supplemental O 2 (hyperoxia) in premature infants detrimentally affects bronchial airways leading to increased senescence. Understanding the mechanisms by which hyperoxia initiates senescence in developing airways is critical for future therapeutic strategies. The current study showed that hyperoxia-induced senescence is mediated through increased mitochondrial reactive oxygen species and endoplasmic reticulum (ER) stress. ER stress inhibitors or mitochondria-targeted antioxidants may represent future therapies to blunt detrimental effects of supplemental oxygen in developing lungs.

Abstract The lung is an inherently mechanosensitive organ, where cells of the airway and parenchyma experience a range of mechanical forces throughout life including shear, stretch, and compression, in both health and disease. In this regard, pediatric and adult lung diseases such as wheezing and asthma, bronchopulmonary dysplasia (BPD), chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis (PF) all involve macroscopic and cellular changes to the mechanical properties of the bronchial airways and/or parenchyma to varying extents. Accordingly, understanding how mechanical forces are sensed in the lung, and the responses of cells and tissues in the context of normal development and health versus disease conditions becomes highly relevant. There is increasing recognition that transduction of mechanical forces into cellular responses involves a number of channels, some of which are inherently mechanosensitive. Such channels trigger mechanotransduction pathways that may further mediate cellular remodeling, inflammation, and other pathophysiologic mechanisms in response to stretch, stiffness, and inflammatory cascades. Two particularly important channel families have emerged in pulmonary pathophysiology: the transient receptor potential vanilloid family with focus on member TRPV4 and the recently identified Piezo (PZ) channels. Here, we explore current understanding of the contributions of TRPV4 and PZ channels in lung health and disease states, focusing on the interactions between these mechanosensitive channels and their local environment including immune cells, the extracellular matrix, and cellular cytoskeletal elements. We further discuss potential areas for future research to better understand the impact of mechanical channels on pulmonary health and disease. © 2023 American Physiological Society. Compr Physiol 13:5157‐5178, 2023.

Abstract The lung parenchyma comprises a large number of thin‐walled alveoli, forming an enormous surface area, which serves to maintain proper gas exchange. The alveoli are held open by the transpulmonary pressure, or prestress, which is balanced by tissues forces and alveolar surface film forces. Gas exchange efficiency is thus inextricably linked to three fundamental features of the lung: parenchymal architecture, prestress, and the mechanical properties of the parenchyma. The prestress is a key determinant of lung deformability that influences many phenomena including local ventilation, regional blood flow, tissue stiffness, smooth muscle contractility, and alveolar stability. The main pathway for stress transmission is through the extracellular matrix. Thus, the mechanical properties of the matrix play a key role both in lung function and biology. These mechanical properties in turn are determined by the constituents of the tissue, including elastin, collagen, and proteoglycans. In addition, the macroscopic mechanical properties are also influenced by the surface tension and, to some extent, the contractile state of the adherent cells. This chapter focuses on the biomechanical properties of the main constituents of the parenchyma in the presence of prestress and how these properties define normal function or change in disease. An integrated view of lung mechanics is presented and the utility of parenchymal mechanics at the bedside as well as its possible future role in lung physiology and medicine are discussed. © 2011 American Physiological Society. Compr Physiol 1:1317‐1351, 2011.