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Background Incidental findings (IFs) are common on low dose CT obtained during lung cancer screening (LCS). The identification and management of clinically significant IFs is a challenging aspect of LCS programs and there is no standardized method of reporting IFs to primary care providers or patients. We explored the prevalence of incidental findings and radiologist use of the “S” modifier to identify clinically significant findings compared to what the LCS team identified as a clinically significant finding. We also presented a standardized reporting approach that provides suggested actions for providers and patients. Methods We conducted a review of a sample of low-dose CT scans of the chest reported between August 17, 2023 and April 29, 2024 completed at VA Boston Healthcare System, omitting scans with findings concerning for lung cancer. We assessed the reporting of incidental findings by the radiologist, compared this to identification of clinically significant incidental findings by the lung cancer screening team, and evaluated factors associated with number and occurrence of incidental findings (via complete case regression). Results Among 495 patients (Mean Age: 69.0 (6.6), 94.4% Male, 53.2% Current Smoker), 444 scans were retained for analysis. Scans had a median of seven incidental findings. The most common incidental finding was multiple pulmonary nodules (77.9%). There were 165 low-dose CT with findings the lung cancer screening team considered clinically important, however, radiologists only assigned the “S” modifier to 35 scans. Conclusions All scans reviewed had incidental findings and nearly 40% had a finding that was clinically significant to the lung cancer screening team. There was inconsistent reporting between the radiologists and lung cancer screening team on clinical significance. Radiologists identified fewer clinically important findings than the lung cancer screening team and applied the “S” modifier inconsistently. There is no standardized method for reporting clinically significant low-dose CT results to primary care providers or patients. Our approach provides a structured approach, acknowledges multiple clinical opinions, and provides a framework for communication.

Inhaled treprostinil was approved recently for interstitial lung disease‐pulmonary hypertension; however, efficacy in “real‐world” populations is not known. We designed a protocol and report our experience evaluating 10 patients referred for therapy. Misdiagnosis at presentation was common; ultimately, three patients (30%) were prescribed drug. This protocol offers an opportunity to standardize longitudinal assessment of inhaled treprostinil in clinical practice.

Treating Veterans with chronic obstructive pulmonary disease complicated by pulmonary hypertension (COPD‐PH) using phosphodiesterase type‐5 inhibitor pharmacotherapy is common, but efficacy data are lacking. To address this further, patients with COPD‐PH from five Department of Veterans Affairs hospitals were randomized (1∶1) to receive placebo or oral tadalafil (40 mg/day) for 12 months. The primary endpoint was changed from baseline in 6‐min walk distance at 12 months. Secondary endpoints included change from baseline in pulmonary vascular resistance, mean pulmonary artery pressure, and symptom burden by the University of California San Diego shortness of breath questionnaire scale at 6 months. A total of 42 subjects (all male; 68 ± 7.6 years old) were randomized to placebo (N = 14) or tadalafil (N = 28). The group imbalance was related to under‐enrollment. Compared to placebo, no significant difference was observed in the tadalafil group for change from the primary endpoint or change in mean pulmonary artery pressure or pulmonary vascular resistance from baseline at 6 months. A clinically meaningful improvement was observed in the secondary endpoint of shortness of breath questionnaire score in the tadalafil versus placebo group at 6 months. There was no significant difference in major adverse events between treatment groups, and tadalafil was well tolerated overall. For Veterans with COPD‐PH enrolled in this study, once‐daily treatment with tadalafil did not improve 6‐min walk distance or cardiopulmonary hemodynamics although a decrease in shortness of breath was observed. Under‐enrollment and imbalanced randomization confound interpreting conclusions from this clinical trial and limit the generalization of our findings.

A prominent feature of fibrotic tissue in general and of lungs in particular is fibroblast proliferation and accumulation. In patients overcoming fibrosis, apoptosis limits this excessive cell growth. We have previously shown resistance to Fas-induced apoptosis of primary lung fibroblasts from mice with bleomycin-induced lung fibrosis, their escape from immune surveillance, and continued accumulation in spite of overexpression of the Fas death receptor. Cellular FLICE-like inhibitory protein (c-FLIP) is a regulator of cell death receptor–induced apoptosis in many cell types. We aimed to determine c-FLIP levels in myofibroblasts from fibrotic lungs and to directly assess c-FLIP’s role in apoptosis and proliferation of primary lung myofibroblasts. c-FLIP levels were determined by apoptosis gene array, flow cytometry, Western blot, and immunofluorescence before and after down-regulation with a specific small interfering RNA. Apoptosis was assessed by caspase cleavage in Western blot and by Annexin V affinity labeling after FACS and tissue immunofluorescence. Proliferation was assessed by BrdU uptake, also using FACS and immunofluorescence. We show that myofibroblasts from lungs of humans with idiopathic pulmonary fibrosis and from bleomycin-treated versus normal saline-treated mice up-regulate c-FLIP levels. Using the animal model, we show that fibrotic lung myofibroblasts divert Fas signaling from apoptosis to proliferation and that this requires signaling by TNF receptor–associated factor (TRAF) and NF-κB. c-FLIP down-regulation reverses the effect of Fas activation, causing increased apoptosis, decreased proliferation, and diminished recruitment of TRAF to the DISC complex. This indicates that c-FLIP is essential for myofibroblast accumulation and may serve as a potential target to manipulate tissue fibrosis.

Invasive cardiopulmonary exercise testing (iCPET) combines full central hemodynamic assessment with continuous measurements of pulmonary gas exchange and ventilation to help in understanding the pathophysiology underpinning unexplained exertional intolerance. There is increasing evidence to support the use of iCPET as a key methodology for diagnosing heart failure with preserved ejection fraction and exercise-induced pulmonary hypertension as occult causes of exercise limitation, but there is little information available outlining the methodology to use this diagnostic test in clinical practice. To bridge this knowledge gap, the operational protocol for iCPET at our institution is discussed in detail. In turn, a standardized iCPET protocol may provide a common framework to describe the evolving understanding of mechanism(s) that limit exercise capacity and to facilitate research efforts to define novel treatments in these patients.

A single intratracheal dose of porcine pancreatic elastase, which is cleared from the lung by 24 hours, was administered to wild-type, IL-1β type 1 receptor-deficient, double TNF-α (type 1 and type 2) receptor-deficient, and combined TNF-α (type 1 receptor) plus IL-1β receptor-deficient mice. The mean linear intercept (Lm) of saline-treated mice was 32(3) μm [mean(SE)]. For wild-type elastase-treated mice, Lm was 81(6) μm at 21 days versus 52(5) μm at 5 days after treatment, indicating that alveolar wall remodeling occurs long after the elastase injury. At 21 days, Lm values were 67(10), 62(3), and 39(5) μm in elastase-treated mice deficient in the IL-1β receptor, double TNF-α receptors, and combined receptors, respectively. The level of apoptosis assessed by a terminal deoxynucleotidyl transferase-catalyzed in situ nick end-labeling assay was increased at 5 days after elastase treatment and was markedly and similarly attenuated in the IL-1β, the double TNF-α, and the combined receptor-deficient mice. Our results indicate that inflammatory mediators exacerbate elastase-induced emphysema. We estimate that in the combined TNF-α + IL-1β receptor-deficient mice, inflammation accounts for about 80% of the emphysema that develops after elastase treatment; decreased apoptosis of lung cells likely contributes to decreased severity of emphysema.

The objective of this study was to investigate the histology of tissue formed when fetal rat lung cells were grown in a collagen-glycosaminoglycan (GAG) tissue-engineering scaffold. The goal was the formation of lung histotypic structures in the tissue-engineering scaffolds in vitro . Achieving this goal would facilitate future investigations of the effects of selected scaffold design parameters on processes that may underlie aspects of lung regeneration in vivo. Lung cells were obtained from Sprague-Dawley rats after 16 and 19 days of gestation. These dissociated cells were seeded into type I collagen-chondroitin 6-sulfate matrices, 8 mm in diameter by 2 mm in thickness, cross-linked and sterilized by dehydrothermal treatment. Approximately 28 million cells were seeded into each spongelike sample. Histological and immunohistochemical studies were performed at termination periods of 2 days and 1, 2, and 3 weeks. The enzymatically dissociated 19-day gestation fetal rat lung cells formed and maintained alveolar-like structures, 50-60 µm in diameter, in the collagen- GAG scaffold. A novel finding was that all of the cell-seeded scaffolds underwent cell-mediated contraction that appeared to be associated with the finding by immunohistochemistry of expression of α-smooth muscle actin in some cells. These results demonstrate the capability of dissociated lung cells to form lung histotypic structures in collagen-GAG tissue-engineering scaffolds in vitro . This culture system may be of value in facilitating exploration of strategies for preparing such scaffolds for the regeneration of lung tissue in vivo .