Search

Background and Purpose: Toll‐like receptors 4 (TLR4) and TLR7/TLR8 play an important role in mediating the inflammatory effects of bacterial and viral pathogens. Interleukin‐1 receptor‐associated kinase 4 (IRAK4) is an important regulator of signalling by toll‐like receptor (TLR) and hence is a potential therapeutic target in diseases characterized by increased lung inflammatory signalling. Experimental Approach: We used an established murine model of acute lung inflammation, and studied human lung tissue ex vivo, to investigate the effects of inhibiting IRAK4 on lung inflammatory pathways. Key Results: We show that TLR4 stimulation produces an inflammatory response characterized by neutrophil influx and tumour necrosis factor‐α (TNF‐α) production in murine lungs and that these responses are markedly reduced in IRAK4 kinase‐dead mice. In addition, we characterize a novel selective IRAK4 inhibitor, BI1543673, and show that this compound can reduce lipopolysaccharide (LPS)‐induced airway inflammation in wild‐type mice. Additionally, BI1543673 reduced inflammatory responses to both TLR4 and TLR7/8 stimulation in human lung tissue studied ex vivo. Conclusion and Implications: These data demonstrate a key role for IRAK4 signalling in lung inflammation and suggest that IRAK4 inhibition has potential utility to treat lung diseases characterized by inflammatory responses driven through TLR4 and TLR7/8. [ABSTRACT FROM AUTHOR]

Background: Ventilator‐associated pneumonia (VAP) is a significant concern in low‐middle‐income countries (LMICs), where the burden of hospital‐acquired infections is high, and resources are low. Evidence‐based guidelines exist for preventing VAP; however, these guidelines may not be adequately utilized in intensive care units of LMICs. Aim: This scoping review examined the literature regarding the use of nursing care bundles for VAP prevention in LMICs, to understand the knowledge, practice and compliance of nurses to these guidelines, as well as the barriers preventing the implementation of these guidelines. Study Design: The review was conducted using Arksey and O'Malley's (2005) five‐stage framework and the PRISMA‐ScR guidelines guided reporting. Searches were performed across six databases: CINAHL, Medline, Embase, Global Health, Scopus and Cochrane, resulting in 401 studies. Results: After screening all studies against the eligibility criteria, 21 studies were included in the data extraction stage of the review. Across the studies, the knowledge and compliance of nurses regarding VAP prevention were reported as low to moderate. Several factors, ranging from insufficient knowledge to a lack of adequate guidelines for VAP management, served as contributing factors. Multiple barriers prevented nurses from adhering to VAP guidelines effectively, including a lack of audit/surveillance, absence of infection prevention and control (IPC) teams and inadequate training opportunities. Conclusions: This review highlights the need for adequate quality improvement procedures and more efforts to conduct and translate research into practice in intensive care units in LMIC. Relevance to Clinical Practice: IPC practices are vital to protect vulnerable patients in intensive care units from developing infections and complications that worsen their prognosis. Critical care nurses should be trained and reinforced to practice effective bundle care to prevent VAP. [ABSTRACT FROM AUTHOR]

Background: Inflammation and immunity contribute pivotally to diverse acute and chronic diseases. Inflammatory pathways have become increasingly targets for therapy. Yet, despite substantial similarity in mechanisms and pathways, the scientific, medical, pharma and biotechnology sectors have generally focused programs finely on a single disease entity or organ system. This insularity may impede progress in innovation and the harnessing of powerful new insights into inflammation biology ripe for clinical translation. Methods: A multidisciplinary thinktank reviewed highlights how inflammation contributes to diverse diseases, disturbed homeostasis, ageing and impaired healthspan. We explored how common inflammatory and immune mechanisms that operate in key conditions in their respective domains. This consensus review highlights the high degree of commonality of inflammatory mechanisms in a diverse array of conditions that together contribute a major part of the global burden of morbidity and mortality and present an enormous challenge to public health and drain on resources. Results: We demonstrate how that shared inflammatory mechanisms unite many seemingly disparate diseases, both acute and chronic. The examples of infection, cardiovascular conditions, pulmonary diseases, rheumatological disorders, dementia, cancer and ageing illustrate the overlapping pathogenesis. We outline opportunities to synergize, reduce duplication and consolidate efforts of the clinical, research and pharmaceutical communities. Enhanced recognition of these commonalties should promote cross‐fertilization and hasten progress in this rapidly moving domain. Conclusions: Greater appreciation of the shared mechanisms should simplify understanding seemingly disparate diseases for clinicians and help them to recognize inflammation as a therapeutic target which the development of novel therapies is rendering actionable. [ABSTRACT FROM AUTHOR]

Background: Although swallowing impairment is prevalent following lung transplantation, baseline respiratory and swallowing characteristics are often overlooked. Respiratory disease processes may predispose lung transplant candidates to altered respiratory‐swallow patterning and swallowing impairment. Methods: This cross‐sectional study included patients referred for a Modified Barium Swallow Study during lung transplant evaluation. Swallowing impairment was measured using the Modified Barium Swallow Impairment Profile and Penetration‐Aspiration Scale. Respiratory plethysmographic signals synchronized with videofluoroscopy were analyzed to determine phase patterning, pause duration, and rate. Mixed‐effects logistic regression was used to identify linkages between respiratory and swallowing measures. Key Results: Fifty patients were included and demonstrated delayed swallow initiation (49/50), oral residue (37/50), incomplete pharyngoesophageal segment opening (35/50), and esophageal retention (43/50). Airway invasion occurred infrequently (10/50). Atypical respiratory patterning was significantly associated with impairment in pharyngeal swallow initiation (OR [95% CI] = 1.76 [1.16, 2.68], p = 0.009), laryngeal elevation (OR [95% CI] = 1.45 [1.01, 2.07], p = 0.044), and laryngeal vestibular closure (OR [95% CI] = 2.57 [1.48, 4.46], p < 0.001). Increased pause duration was associated with impaired initiation (OR [95% CI] = 2.24 [1.20, 4.16], p = 0.011), laryngeal elevation (OR [95% CI] = 1.18 [1.03, 1.36], p = 0.018), laryngeal closure (OR [95% CI] = 1.28 [1.9, 1.50], p = 0.003), and tongue base retraction (OR [95% CI] = 1.33 [1.13, 1.56], p < 0.001). Conclusions & Inferences: Patients undergoing evaluation for lung transplant demonstrated impaired swallowing and phase patterning. Preliminary findings implicate the need for further evaluation of respiratory‐swallow coordination and its potential role in swallowing impairment before and after lung transplantation. [ABSTRACT FROM AUTHOR]

Phase‐resolved functional lung (PREFUL) MRI is a proton‐based, contrast agent‐free technique derived from the Fourier decomposition approach to measure regional ventilation and perfusion dynamics during free‐breathing. Besides the necessity of extensive PREFUL postprocessing, the utilized MRI sequence must fulfill specific requirements. This study investigates the impact of sequence selection on PREFUL‐MRI–derived functional parameters by comparing the standard spoiled gradient echo (SPGRE) sequence with a lung‐optimized balanced steady‐state free precession (bSSFP) sequence, thereby facilitating PREFULs clinical application in pulmonary disease assessment. This study comprised a prospective dataset of healthy volunteers and a retrospective dataset of patients with suspected chronic thromboembolic pulmonary hypertension. Both cohorts underwent PREFUL‐MRI with both sequences to assess the correspondence of PREFUL ventilation and perfusion parameters (A). Additionally, healthy subjects were scanned a second time to evaluate repeatability (B), whereas patients received dynamic contrast‐enhanced (DCE)‐MRI, considered the perfusion gold standard for comparison with PREFUL‐MRI (C). Signal‐to‐noise ratio (SNR), calculated from the unprocessed images, was compared alongside median differences of PREFUL‐MRI–derived parameters using a paired Wilcoxon signed rank test. Further evaluations included calculation of the Pearson correlation, intraclass‐correlation coefficient for repeatability assessment, and spatial overlap (SO) for regional comparison of PREFUL‐MRI and DCE‐MRI. bSSFP showed a clear SNR advantage over SPGRE (median: 23 vs. 9, p < 0.001). (A) Despite significant differences, parameter values were strongly correlated (r ≥ 0.75). After thresholding, binary maps showed high healthy overlap across both cohorts (SOHealthy > 86%) and high defect overlap in the patient cohort (SODefect ≥ 48%). (B) bSSFP demonstrated slightly higher repeatability across most parameters. (C) Both sequences demonstrated comparable correspondence to DCE‐MRI, with SPGRE excelling in absolute quantification and bSSFP in spatial agreement. Although bSSFP showed superior SNR results, both sequences displayed spatial defect concordance and highly correlated PREFUL parameters with deviations regarding repeatability and alignment with DCE‐MRI. [ABSTRACT FROM AUTHOR]

Hypersensitivity pneumonitis (HP) is an immune‐mediated interstitial lung disease (ILD) relating to specific occupational, environmental or medication exposures. Disease behaviour is influenced by the nature of exposure and the host response, with varying degrees of lung inflammation and fibrosis seen within individuals. The differentiation of HP from other ILDs is important due to distinct causes, pathophysiology, prognosis and management implications. This Thoracic Society of Australia and New Zealand (TSANZ) position statement aims to provide an up‐to‐date summary of the evidence for clinicians relating to the diagnosis and management of HP in adults, in the Australian and New Zealand context. This document highlights recent relevant findings and gaps in the literature for which further research is required. [ABSTRACT FROM AUTHOR]

SUMMARY OF KEY POINTS In this review, we have discussed several important developments in 2023 in Interstitial Lung Disease (ILD). The association of pollution with genetic predispositions increased the risk of Idiopathic Pulmonary Fibrosis (IPF). An interesting comorbidity of malnutrition was not adequately recognized in ILD. Novel genes have been identified in IPF involving predominantly short telomere length and surfactant protein production leading to alveolar epithelial cell dysfunction. Genetics also predicted progression in IPF. Crosstalk between vascular endothelial cells and fibroblasts in IPF mediated by bone morphogenic protein signalling may be important for remodelling of the lung. A novel modality for monitoring of disease included the 4‐min gait speed. New treatment modalities include inhaled pirfenidone, efzofitimod, for sarcoidosis, and earlier use of immunosuppression in connective tissue disease‐ILD. [ABSTRACT FROM AUTHOR]

Aims Methods and Results Conclusion Giant cell interstitial pneumonia (GIP) is a fibrosing lung disease histologically characterized by centrilobular pulmonary fibrosis and cannibalistic intra‐alveolar multinucleated giant cells. It is considered a form of pneumoconiosis caused particularly by secondary exposure to hard metals (cemented carbide or tungsten carbide). Hard metals are commonly used in various industrial applications, such as cutting tools, drilling tools, machine inserts, and other wear‐resistant components. However, cases with unknown exposure that recurred in transplanted lungs have been described. This has led to the hypothesis of a complex etiopathogenesis, likely multifactorial, involving the coparticipation of immune mechanisms. We aimed to identify all the elements present in a series of GIP lung samples to better understand the pathogenic mechanisms of the disease.We describe five cases of histologically diagnosed GIP in patients with occupational exposure to metallic dust using ultrastructural characterization to identify metal dust and to quantify asbestos fibres. We found that tungsten was present in three cases, albeit in trace amounts in two of them. Numerous elements were identified in all samples, including asbestos fibres in patients with endstage pulmonary fibrosis. Furthermore, in one of the described cases the recurrence of the disease was also observed in transplanted lungs.These findings support the hypothesis that GIP may be due to elements other than hard metals, with asbestos possibly representing a contributory factor in the expression of a more severe fibrotic disease. The recurrence of GIP observed in transplanted organs strengthens the hypothesis of the existence of a not yet fully understood etiopathogenic immune mechanism. [ABSTRACT FROM AUTHOR]

Summary The NLRP3 inflammasome is a multiprotein complex that upon activation by the innate immune system drives a broad inflammatory response. The primary initial mediators of this response are pro‐IL‐1β and pro‐IL‐18, both of which are in an inactive form. Formation and activation of the NLRP3 inflammasome activates caspase‐1, which cleaves pro‐IL‐1β and pro‐IL‐18 and triggers the formation of gasdermin D pores. Gasdermin D pores allow for the secretion of active IL‐1β and IL‐18 initiating the organism‐wide inflammatory response. The NLRP3 inflammasome response can be beneficial to the host; however, if the NLRP3 inflammasome is inappropriately activated it can lead to significant pathology. While the primary components of the NLRP3 inflammasome are known, the precise details of assembly and activation are less well defined and conflicting. Here, we discuss several of the proposed pathways of activation of the NLRP3 inflammasome. We examine the role of subcellular localization and the reciprocal regulation of the NLRP3 inflammasome by autophagy. We focus on the roles of mitochondria and mitophagy in activating and regulating the NLRP3 inflammasome. Finally, we detail the impact of pathologic NLRP3 responses in the development and manifestations of pulmonary disease. [ABSTRACT FROM AUTHOR]

Interstitial lung diseases (ILDs) include a variety of inflammatory and fibrotic pulmonary conditions. This study employs high‐resolution metabolomics (HRM) to explore plasma metabolites and pathways across ILD phenotypes, including non‐fibrotic ILD, idiopathic pulmonary fibrosis (IPF), and non‐IPF fibrotic ILD. The study used 80 plasma samples for HRM, and involved linear trend and group‐wise analyses of metabolites altered in ILD phenotypes. We utilized limma one‐way ANOVA and mummichog algorithms to identify differences in metabolites and pathways across ILD groups. Then, we focused on metabolites within critical pathways, indicated by high pathway overlap sizes and low p‐values, for further analysis. Targeted HRM identified putrescine, hydroxyproline, prolyl‐hydroxyproline, aspartate, and glutamate with significant linear increases in more fibrotic ILD phenotypes, suggesting their role in ILD fibrogenesis. Untargeted HRM highlighted pathway alterations in lysine, vitamin D3, tyrosine, and urea cycle metabolism, all associated with pulmonary fibrosis. In addition, methylparaben level had a significantly increasing linear trend and was higher in the IPF than fibrotic and non‐ILD groups. This study highlights the importance of specific amino acids, metabolic pathways, and xenobiotics in the progression of pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

Lung diseases are one of the leading causes of global mortality. Advances in induced pluripotent stem cell (iPSC) differentiation have enabled the creation of bronchiolar and alveolar lung organoids, advancing research on lung conditions. Traditional Matrigel encapsulation, reliant on the spontaneous assembly and propagation of cells with limited external intervention, often results in variability and low reproducibility. The absence of hyaluronic acid (HA) in Matrigel, a key lung extracellular matrix component, limits bronchiolar and alveolar cell differentiation, reducing the efficacy and reproducibility of iPSC‐derived organoid generation. To address this, a novel hybrid hydrogel combining HA and 23% Matrigel, inspired by the natural lung environment, is developed. This hydrogel offers improved biochemical support and viscoelastic properties, significantly accelerating organoid development. Within eight days, the hydrogel produces uniformly sized organoids containing both bronchiolar and alveolar epithelial cells. Increased levels of active mechanosensors and transducers, including PIEZO1, Integrin, and Myosin, suggest that the hydrogel's altered viscoelasticity triggers a mechanotransduction cascade. This bioinspired hydrogel provides a robust, fast model for biomedical research, facilitating rapid drug screening, respiratory disease treatment studies, and surfactant trafficking investigations. Furthermore, it enables the exploration of underlying biomechanical mechanisms to enhance the controllability of organoid generation and maturation. [ABSTRACT FROM AUTHOR]

Background and Purpose: To examine the respiratory and functional benefits of manual diaphragmatic release for Cleaning‐Laborers Exposed to Occupational Hazards. Methods: A randomized controlled trial of 36 participants aged 35–45 years was randomly allocated into two groups. The experimental group (n = 18); received manual diaphragm release along with respiratory training exercises, and the control group (n = 18); received respiratory training exercises only. Three times/week for 12 consecutive weeks. The serum immunoglobulin E level, pulmonary functions [forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1/FVC, and peak expiratory flow (PEF) rate (PEF)], chest wall mobility, and 6 min walk‐test performance were assessed pre‐ and post‐intervention. Results: There was a greater decline in serum immunoglobulin levels (p = 0.003; Partial η2 = 0.23) and enhancement in pulmonary functions [FEV1 (p = 0.025, Partial η2 = 0.14), FVC (p = 0.017, Partial η2 = 0.16), FEV1/FVC (p = 0.028, Partial η2 = 0.13), and PEF (p = 0.012, Partial η2 = 0.17) in the experimental group. Further, there was a greater increase in chest mobility at the xiphoid level (p = 0.002, Partial η2 = 0.25) in the experimental group, but this was not the case at the axillary level (p = 0.29, Partial η2 = 0.03). Still, the 6 min walk‐test performance improved more significantly in the experimental group (p = 0.002, Partial η2 = 0.24). Conclusion: The diaphragmatic release technique may offer a promising approach for mitigating distressing respiratory symptoms, enhancing immune function, and improving 6 min walk‐test performance among cleaning laborers with work‐related respiratory hazards. Trial registration: The study was retrospectively registered at XXX (ID: NCT05802355). [ABSTRACT FROM AUTHOR]

Introduction: Center‐based rehabilitation is limited by COVID‐19 infectivity and social distancing policy. We hypothesized that discharged patients benefit from 8‐week home‐based tele‐rehabilitation (tele‐PR) using mobile phones and low‐cost instruments. Methods: The TERCOV (Tele‐rehabilitation in COVID‐19 survivors) is an investigator‐initiated, prospective, multi‐center, real‐world study. After proper assessment, 186 discharge patients received tele‐PR by smartphone, including breathing exercise, respiratory muscle training, aerobic exercise, and resistance training. Physicians, physiotherapists, and nurses provided guidance through smartphone applications. The primary outcome was six‐minute walk distance (6MWD). The secondary outcomes included hand grip, short physical performance battery, maximal inspiratory pressure, maximal expiratory pressure, self‐rating anxiety/depression scale (SAS/SDS), 36‐item short‐form health survey (SF‐36) and international physical activity questionnaire. Results: Dyspnea subgroups were more functionally impaired. After tele‐PR, improvements were observed in exercise capacity(∆6MWD: 16.80 m, 95% CI 1.18–32.42, p < 0.0001), limb muscle function (∆SPPB 0.25 points, 95% CI 0.05–0.46), respiratory muscle strength (∆MIP 16.50 cm H2O, 95% CI 9.22–23.78, p < 0.0001; ∆MEP: 12.09 cm H2O, 95% CI 3.48–20.70, p = 0.0002), health‐related quality of life (∆SF‐36 49.85, 95% CI: 21.01–78.69, p < 0.0001), physical activity(∆HEPA 13.01%, p = 0.0029). Anxiety reduced in patients with mMRC ≥ 2 (∆SAS = −4.19 points, CI −8.16 to −0.22, p = 0.03). Greater change was seen in dyspnea patients. Implications on Physiotherapy Practice: Supervised/semi‐supervised tele‐PR is a promising option during the pandemic. Patients with Dyspnea benefit more. [ABSTRACT FROM AUTHOR]

A 31‐week gestation male infant with respiratory distress since day of delivery had lobectomy at 8 weeks of age for symptomatic, suspected congenital pulmonary airway malformation (CPAM). Histology of resected lung showed cytomegalovirus (CMV) inclusion bodies and emphysematous changes. The infant was treated with antiviral therapy with improvement in symptoms. CMV infection of the lung should be considered in any neonate presenting with lung cysts. [ABSTRACT FROM AUTHOR]

The high risk of patients with chronic lung diseases in developing into lung cancer has been recognised, but the key factors driving such procedure are still barely known. Dendritic cells (DCs) as major antigen presenting cells take part in the immune response in the very upstream, and myeloid DCs regulate the inflammation in pulmonary diseases. In this article, we performed single‐cell RNA sequencing (scRNA‐seq) analyses on DCs from pulmonary diseases. We explore the DC characteristics in chronic lung diseases, lung cancer and healthy control samples. We discover that a special type of DC, which is highly associated with inflammatory, inf‐DC, is abundant in lung cancer samples. Furthermore, we find that there are about 10% patients with chronic lung diseases also has such inf‐DC‐rich pattern. Such proportion is consistent to the fact that about 10% chronic lung disease patients finally developed into cancer. Our findings indicate inf‐DC could be a potential factor to predict the risk of chronic lung disease developing into cancer. [ABSTRACT FROM AUTHOR]

Background: Lung transplant recipients (LTRs) are at risk for Mycobacterium avium complex (MAC) infections, in part due to the presence of structural lung disease pre‐transplant and relatively higher levels of immunosuppression post‐transplant. There is a lack of data regarding outcomes of LTR with MAC infections pre‐transplant. Methods: This is a single‐center retrospective analysis of patients who received lung transplants (LTs) from 2013 to 2020 with 1) evidence of MAC on culture or polymerase chain reaction before or at the time of transplant or 2) granulomas on explant pathology and positive acid‐fast bacillus stains with no other mycobacteria identified. Patients were deemed to have MAC pulmonary disease (MAC‐PD) if they met the American Thoracic Society/Infectious Disease Society of America criteria. Results: Fourteen patients (14/882, 2%) met inclusion criteria. Seven patients (7/14, 50%) had pre‐transplant MAC‐PD, four of whom had cavitary disease. None of the 14 patients had smear‐positive cultures at the time of transplant. Two patients in our cohort received treatment for MAC before transplant. Thirteen patients were bilateral LTR (13/14, 93%). One single LTR was the sole patient to receive MAC treatment post‐transplant. No patients developed MAC‐PD after transplant. Conclusion: The bilateral LTR in our cohort did not develop MAC‐PD despite not receiving MAC treatment post‐transplant. It is possible source control was achieved with native lung explantation. Our observations suggest patients may not uniformly require pre‐ or post‐transplant MAC treatment if they are smear‐negative and undergo bilateral LT. [ABSTRACT FROM AUTHOR]

Background: Primary spontaneous pneumothorax occurs in patients with no underlying lung disease and guidelines recommend chest tube drainage for the first episode, with surgical intervention reserved for recurrent episodes, persistent air leak or failure of lung re‐expansion. Modern surgical management is associated with reduced length of hospital stay and superior freedom from recurrence compared with chest tube drainage alone. The objective of this study was to identify risk factors for failed chest tube drainage in patients who present with first episode primary spontaneous pneumothorax. Methods: A retrospective analysis of patients who presented to Royal Prince Alfred Hospital, Australia with first episode PSP and underwent chest tube insertion was performed. Patient demographics and size of pneumothorax were examined in relation to the primary outcome, a composite of failed chest tube drainage and recurrent ipsilateral pneumothorax. Results: Fifty‐five patients underwent chest tube drainage for first episode primary spontaneous pneumothorax between 1st January 2017 and 31st December 2020. Complete lung collapse on admission chest x‐ray was associated with an increased risk of the primary outcome (63% versus 19%, OR 7.3 [96% CI 2.0–27.4), P = 0.004). Conclusion: This small retrospective study found that patients that undergo chest drain insertion for first episode primary spontaneous pneumothorax who present with complete lung collapse on admission are at high risk of requiring pleurodesis and therefore may benefit from early surgical referral. [ABSTRACT FROM AUTHOR]

Age‐related chronic inflammatory lung diseases impose a threat on public health, including idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). However, their etiology and potential targets have not been clarified. We performed genome‐wide meta‐analysis for IPF with the largest sample size (2883 cases and 741,929 controls) and leveraged the summary statistics of COPD (17,547 cases and 617,598 controls). Transcriptome‐wide and proteome‐wide Mendelian randomization (MR) designs, together with genetic colocalization, were implemented to find robust targets. The mediation effect was assessed using leukocyte telomere length (LTL). The single‐cell transcriptome analysis was performed to link targets with cell types. Individual‐level data from UK Biobank (UKB) were used to validate our findings. Sixteen genetically predicted plasma proteins were causally associated with the risk of IPF and 6 proteins were causally associated with COPD. Therein, genetically‐elevated plasma level of SCARF2 protein should reduce the risk of both IPF (odds ratio, OR = 0.9974 [0.9970, 0.9978]) and COPD (OR = 0.7431 [0.6253, 0.8831]) and such effects were not mediated by LTL. Genetic colocalization further corroborated these MR results of SCARF2. The transcriptome‐wide MR confirmed that higher expression level of SCARF2 was associated with a reduced risk of both. However, the single‐cell RNA analysis indicated that SCARF2 expression level was only relatively lower in epithelial cells of COPD lung tissue compared to normal lung tissue. UKB data implicated an inverse association of serum SCARF2 protein with COPD (hazard ratio, HR = 1.215 [1.106, 1.335]). The SCARF2 gene should be a novel target for COP. [ABSTRACT FROM AUTHOR]

Objective: About 3% of patients with lupus develop severe diffuse alveolar hemorrhage (DAH) with pulmonary vasculitis. C57BL/6 (B6) mice with pristane‐induced lupus also develop DAH, but BALB/c mice are resistant. DAH is independent of Toll‐like receptor signaling and other inflammatory pathways. This study examined the role of the MEK1/2 pathway (MEK1/2–ERK1/2, JNK, p38). Methods: B6 and BALB/c mice were treated with pristane with or without inhibitors of MEK1/2 (trametinib/GSK1120212 [GSK]), ERK1/2 (SCH772984 [SCH]), JNK, or p38. Effects on lung hemorrhage and hemostasis were determined. Results: GSK and SCH abolished DAH, whereas JNK and p38 inhibitors were ineffective. Apoptotic cells were present in lung samples from pristane‐treated mice but not in mice receiving pristane and GSK, and endothelial dysfunction was normalized. Expression of the ERK1/2‐regulated transcription factor early growth response 1 increased in pristane‐treated B6, but not BALB/c, mice and was normalized by GSK. Pristane also increased expression of the anticoagulant genes Tfpi and Thbd in B6 mice. The ratio of Tfpi to tissue factor (F3) to Tfpi increased in B6 (but not BALB/c) mice and was normalized by GSK. Circulating thrombomodulin protein levels increased in B6 mice and returned to normal after GSK treatment. Consistent with augmented endothelial anticoagulant activity, pristane treatment increased tail bleeding in B6 mice. Conclusion: Pristane treatment promotes lung endothelial injury and DAH in B6 mice by activating the MEK1/2–ERK1/2 pathway and impairing hemostasis. The hereditary factors determining susceptibility to lung injury and bleeding in pristane‐induced lupus are relevant to the pathophysiology of life‐threatening DAH in systemic lupus erythematosus and may help to optimize therapy. [ABSTRACT FROM AUTHOR]

Objectives: Allergic bronchopulmonary aspergillosis (ABPA) is a complex lung disease associated with significant morbidity. The ABPA Working Group (AWG) of the International Society for Human and Animal Mycology (ISHAM) revised their management guidelines in 2024, but there is currently no standardised tool to assess adherence to these recommendations. Methods: We extracted key recommendations from the updated 2024 ISHAM‐AWG guidelines, focusing on critical areas: screening and diagnosis of ABPA, managing acute and treatment‐dependent ABPA, and monitoring treatment response. Each item was assigned a score ranging from zero to three. We assigned negative scores to interventions not recommended by the guidelines. Results: We identified 38 items indicative of optimal clinical care for patients with ABPA. The score for screening asthmatics for ABPA was set at three points. For diagnosing ABPA, 16 items were included, with a score ranging from 12 to 16 points, depending on the specific components used (predisposing conditions, serum A. fumigatus‐specific IgE and IgG, serum total IgE, blood eosinophil count and chest computed tomography). The management of acute ABPA comprised 11 items, with a maximum score of three points. For treatment‐dependent ABPA, there were nine items (scores ranging from −3 to 6). Follow‐up care comprised 10 items with a maximum score of 10–13 points, covering imaging, spirometry, testing serum total IgE levels and therapeutic drug monitoring. Conclusions: The EQUAL ABPA score has been developed as a comprehensive tool to quantify guideline adherence. Future studies will evaluate to which extent guideline adherence is associated with improved clinical outcomes for patients with ABPA. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) pneumonia, often presented as pneumonitis, is characterized by respiratory failure and large interstitial infiltrates visible on chest radiographs. This retrospective cohort study investigates the predictive significance of plasma CMV DNA load on the short‐ and long‐term mortality among immunocompetent patients diagnosed with CMV pneumonia. The study included 61 immunocompetent patients suspected of having CMV pneumonia, treated with intravenous ganciclovir after positive CMV DNA results from bronchoalveolar lavage or plasma. Our multivariate Cox regression analysis identified several independent predictors of mortality. Having idiopathic pulmonary fibrosis (IPF) significantly increased the risk of in‐hospital mortality (HR: 7.27, 95% CI: 1.62–32.52, p = 0.009), as did shorter durations of antiviral therapy (HR: 0.90, 95% CI: 0.84–0.97, p = 0.005) and higher CMV DNA levels (>3870 IU/mL; HR: 9.63, 95% CI: 2.32–39.98, p = 0.002). High CMV DNA levels (>5154 IU/mL) were also predictors of 30‐day mortality (HR: 9.39, 95% CI: 2.20–40.01, p = 0.002). For 1‐year mortality, the presence of IPF (HR: 2.96, 95% CI: 1.08–8.06, p = 0.034), hypersensitivity pneumonia (HP) (HR: 4.30, 95% CI: 1.57–11.78, p = 0.005), shorter duration of total antiviral therapy (HR: 0.95, 95% CI: 0.93–0.99, p = 0.010), and higher CMV DNA levels (>327 IU/mL) (HR: 3.36, 95% CI: 1.33–8.47, p = 0.010) were identified as independent determinants. The study reveals that IPF increases short and long‐term mortality risks, while HP increases long‐term mortality. Extended antiviral treatment duration results in a 10% reduction in in‐hospital mortality for each additional day of treatment. Furthermore, elevated viral loads are associated with higher mortality rates, highlighting the necessity for careful monitoring. [ABSTRACT FROM AUTHOR]

Infection with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) impacts multiple anatomical sites. Whether this is due to the virus itself or is a secondary effect caused by the influx and activation of immune cells is not known. Positron emission tomography (PET) with immunoglobulins can provide insights into which sites and cells are activated in a living animal. Our aim is to use two nanobodies as tools to monitor (1) the distribution of antigen presenting cells (APC) by virtue of their Mafa‐DR expression profile, (2) virus‐infected cells and viral particles using a nanobody against the SARS‐CoV‐2 spike protein. Two [89Zr]‐labeled nanobodies that target the SARS‐CoV‐2 spike protein and major histocompatability complex (MHC) class II antigens (Mafa‐DR), respectively, are used to monitor their distribution during an experimental SARS‐CoV‐2 infection in a nonhuman primate model. Scans are obtained before infection and on Day 3 and 10 post infection (pi) in two macaques each. The [89Zr]anti‐SARS‐CoV‐2 spike nanobody localized to SARS‐CoV‐2‐associated lung lesions and the nasal mucosa, while the [89Zr]anti‐human leukocyte antigen (HLA)‐DR nanobody was predominantly found in non‐affected lung tissue after infection. We also detected, pi, upregulation of the Mafa‐DR signal, indicative of recruitment of professional APCs, in the superior sagittal sinus. [89Zr]‐labeled nanobodies show recruitment of macrophages/monocytes in non‐lesional lung tissue in cynomolgus macaques after experimental infection with SARS‐CoV‐2, as well as accumulation of the spike protein in both lung lesions and the nasal mucosa during infection. These results show the possibility of in vivo monitoring the quality and quantity of immune responses during the initial stages of an infection. [ABSTRACT FROM AUTHOR]

Pulmonary fibrosis (PF) is a chronic and progressive lung disease characterized by extensive alterations of cellular fate and function and excessive accumulation of extracellular matrix, leading to lung tissue scarring and impaired respiratory function. Although our understanding of its pathogenesis has increased, effective treatments remain scarce, and fibrotic progression is a major cause of mortality. Recent research has identified various etiological factors, including genetic predispositions, environmental exposures, and lifestyle factors, which contribute to the onset and progression of PF. Nonetheless, the precise mechanisms by which these factors interact to drive fibrosis are not yet fully elucidated. This review thoroughly examines the diverse etiological factors, cellular and molecular mechanisms, and key signaling pathways involved in PF, such as TGF‐β, WNT/β‐catenin, and PI3K/Akt/mTOR. It also discusses current therapeutic strategies, including antifibrotic agents like pirfenidone and nintedanib, and explores emerging treatments targeting fibrosis and cellular senescence. Emphasizing the need for omni‐target approaches to overcome the limitations of current therapies, this review integrates recent findings to enhance our understanding of PF and contribute to the development of more effective prevention and management strategies, ultimately improving patient outcomes. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the value of 2‐deoxy‐18f‐fluorodeoxyglucose (18F‐FDG) positron emission tomography/computed tomography (PET/CT) and circulating tumor cells (CTCs) for the differential diagnosis of patients with benign lung diseases and those with NSCLC. To explore the phenotypic heterogeneity of CTCs and their correlation with FDG uptake in patients with Stage I–IV NSCLC. Methods: Blood specimens from patients with benign lung diseases and patients with primary NSCLC were collected for the detection of CTCs and their subtypes (epithelial, mixed, and mesenchymal) and analyzed for 18F‐FDG PET/CT tumor metabolic parameters, including the maximum standardized uptake value (SUVmax), standard uptake value (SUL), metabolic tumor volume of primary lesion (MTV), total lesion glycolysis of primary lesion (TLG). Clinical data including age, gender, smoking history, tumor size, TNM stage and pathology type were also collected. The value of the two method alone and in combination for the differential diagnosis of benign and malignant was comparatively analyzed. Finally, the differences in CTC and its subtypes in different stages of NSCLC were compared, and FDG metabolic parameters were correlated with CTC subtypes. Results: There were a total of 65 patients with pulmonary diseases, including 12 patients with benign pulmonary diseases and 53 patients with NSCLC. The mean age was 67 ± 10 (38–89 years), 27 were females and 38 were males. 31 (22 males and 9 females) had a long history of smoking. The mean size of the largest diameter of all single lesions was 36 ± 22 mm with a range of 10–108 mm. Seven out of 12 benign diseases were inflammatory granulomatous lesions and 5 were inflammatory pseudotumours. Twenty‐four out of 53 NSCLC were adenocarcinomas and 29 were squamous carcinomas. Twelve out of 53 patients with NSCLC were in Stage I, 10 were in Stage II, 17 were in Stage III and 14 were in Stage IV. SUVmax, SUL, MTV, TLG, total CTCs, epithelial CTCs, and mixed CTCs were all valuable in the differential diagnosis of benign and malignant. TLG combined with mixed CTCs was statistically different from all other diagnostic methods (p < 0.05) and higher than any other diagnostic criteria. In the differential diagnosis of benign and Stage I NSCLC, only total CTC (Z = −2.188 p = 0.039) and mixed CTCs (Z = −3.020 p = 0.014) had certain diagnostic efficacy, and there was no statistical difference between them (p = 0.480). Only mesenchymal CTCs differed in Stage I–IV NSCLC, with a higher number of those who developed distant metastases than those who had non‐distant metastases. Epithelial CTCs correlated with SUVmax (r = 0.333, p = 0.015) and SUL (r = 0.374, p = 0.006). Mmesenchymal CTCs correlated with MTV (r = 0.342, p = 0.018) and TLG (r = 0.319, p = 0.02). Further subgroup analyses revealed epithelial CTCs were correlated with SUVmax (r = 0.543, p = 0.009) and SUL (r = 0.552, p = 0.008), and the total CTCs was correlated with SUVmax (r = 0.622, p = 0.003), SUL (r = 0.652, p = 0.003), MTV (r = 0.460, p = 0.031), and TLG (r = 0.472, p = 0.027) in the early group (Stage I–II). Only mesenchymal CTCs was associated with MTV (r = 0.369, p = 0.041), and TLG (r = 0.415, p = 0.02) in the intermediate‐late group (Stage III–IV). Conclusion: Both FDG PET metabolic parameters and CTCs demonstrated diagnostic value for NSCLC, and combining TLG with mixed CTCs could enhance their diagnostic efficacy. The total CTCs and mixed CTCs showed greater diagnostic value than FDG PET in distinguishing benign lesions from Stage I NSCLC. In NSCLC patients, the epithelial CTCs exhibited a positive correlation with SUVmax and SUL, while mesenchymal CTCs correlated with MTV, and TLG. Besides, epithelial CTCs showed stronger correlations with SUVmax and SUL, and total CTCs showed stronger correlations with SUVmax, SUL, MTV, and TLG in Stage I–II NSCLC. Only mesenchymal CTCs in Stage III–IV NSCLC showed correlations with MTV and TLG. Stage IV NSCLC cases displayed a higher number of mesenchymal CTCs. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusions Radiation‐induced angiosarcoma (RIAS) of the breast is a rare tumour with high rate of local recurrence. The aim of this study is to evaluate the outcome of radical resections.A retrospective analysis of all patients who underwent extended surgical resection for RIAS of the breast between 2013 and 2022. Included were patients who underwent radical resection, including complete resection of previously irradiated skin and underlying fascia of pectoralis major. Post‐operative and long‐term oncological outcomes were than analysed. A systematic review was performed using the MEDLINE database in the last 20 years.Twenty‐two (n = 22) patients met the inclusion criteria. The median length of the specimen was 220 mm (range, 120–377 mm). At a median follow‐up of 33.5 months (range, 7.9–102.4), 3 (13.6%) patients had both local and metastatic lung disease and 1 (4%) patient with only lung metastasis. The estimated 3‐ and 5‐year OS was 81.1% and 57.9%, respectively. The estimated 3‐ and 5‐year DSS was 91.7% and 65.5%, respectively. The estimated 3‐ and 5‐year DFS rate were both 75.2%. The systematic review identified 17 studies with a recurrence rate ranging from 33% to 100%.Treatment of RIAS of the breast with an up‐front locally extended approach is associated with a low rate of local recurrence compared with the reported literature. [ABSTRACT FROM AUTHOR]

Complete removal of all tumor tissue with a wide surgical margin is essential for the treatment of osteosarcoma (OS). However, it's difficult, sometimes impossible, to achieve due to the invisible small satellite lesions and blurry tumor boundaries. Besides, intraoperative frozen‐section analysis of resection margins of OS is often restricted by the hard tissues around OS, which makes it impossible to know whether a negative margin is achieved. Any unresected small tumor residuals will lead to local recurrence and worse prognosis. Herein, based on the high expression of B7H3 in OS, a targeted probe B7H3‐IRDye800CW is synthesized by conjugating anti‐B7H3 antibody and IRDye800CW. B7H3‐IRDye800CW can accurately label OS areas after intravenous administration, thereby helping surgeons identify and resect residual OS lesions (<2 mm) and lung metastatic lesions. The tumor‐background ratio reaches 4.42 ± 1.77 at day 3. After incubating fresh human OS specimen with B7H3‐IRDye800CW, it can specifically label the OS area and even the microinvasion area (confirmed by hematoxylin‐eosin [HE] staining). The probe labeled area is consistent with the tumor area shown by magnetic resonance imaging and complete HE staining of the specimen. In summary, B7H3‐IRDye800CW has translational potential in intraoperative resection guidance and rapid pathological diagnosis of OS. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Lung cancer screening with low‐dose computed tomography (CT) scans (LDCT) has reduced mortality for patients with high‐risk smoking histories, but it has significant limitations: LDCT screening implementation remains low, high rates of false‐positive scans, and current guidelines exclude those without smoking histories. We sought to explore the utility of liquid biopsy (LBx) in early cancer screening and diagnosis of lung cancer.Using the high‐definition single‐cell assay workflow, we analyzed 99 peripheral blood samples from three cohorts: normal donors (NDs) with no known pathology (n = 50), screening CT patients (n = 25) with Lung‐RADS score of 1–2, and biopsy (BX) patients (n = 24) with abnormal CT scans requiring tissue biopsy.For CT and BX patients, demographic information was roughly equivalent; however, average pack‐years smoked differed. A total of 14 (58%) BX patients were diagnosed with primary lung cancer (BX+). The comparison of the rare event enumerations among the cohorts revealed a greater incidence of total events, rare cells, and oncosomes, as well as specific cellular phenotypes in the CT and BX cohorts compared with the ND cohort. LBx analytes were also significantly elevated in the BX compared with the CT samples, but there was no difference between BX+ and BX− samples.The data support the utility of the LBx in distinguishing patients with an alveolar lesion from those without, providing a potential avenue for prescreening before LDCT. [ABSTRACT FROM AUTHOR]

Background: Auxiliary diagnosis of different types of cystic lung diseases (CLDs) is important in the clinic and is instrumental in facilitating early and specific treatments. Current clinical methods heavily depend on accumulated experience, restricting their applicability in regions with less developed medical resources. Thus, how to realize the computer‐aided diagnosis of CLDs is of great clinical value. Purpose: This work proposed a deep learning‐based method for automatically segmenting the lung parenchyma in computed tomography (CT) slice images and accurately diagnosing the CLDs using CT scans. Methods: A two‐stage deep learning method was proposed for the automatic classification of normal cases and five different CLDs using CT scans. Lung parenchyma segmentation is the foundation of CT image analysis and auxiliary diagnosis. To meet the requirements of different sizes of the lung parenchyma, an adaptive region‐growing and improved U‐Net model was employed for mask acquisition and automatic segmentation. The former was achieved by a self‐designed adaptive seed point selection method based on similarity measurement, and the latter introduced multiscale input and multichannel output into the original U‐Net model and effectively achieved the lightweight design by adjusting the structure and parameters. After that, the middle 30 consecutive CT slice images of each sample were segmented to obtain lung parenchyma, which was employed for training and testing the proposed multichannel parallel input recursive MLP‐Mixer network (MPIRMNet) model, achieving the computer‐aided diagnosis of CLDs. Results: A total of 4718 and 16 290 CT slice images collected from 543 patients were employed to validate the proposed segmentation and classification methods, respectively. Experimental results showed that the improved U‐Net model can accurately segment the lung parenchyma in CT slice images, with the Dice, precision, volumetric overlap error, and relative volume difference of 0.96 ± 0.01, 0.93 ± 0.04, 0.05 ± 0.02, and 0.05 ± 0.03, respectively. Meanwhile, the proposed MPIRMNet model achieved appreciable classification effect for normal cases and different CLDs, with the accuracy, sensitivity, specificity, and F1 score of 0.8823 ± 0.0324, 0.8897 ± 0.0325, 0.9746 ± 0.0078, and 0.8831 ± 0.0334, respectively. Compared with classical machine learning and convolutional neural networks‐based methods for this task, the proposed classification method had a preferable performance, with a significant improvement of accuracy of 10.74%. Conclusions: The work introduced a two‐stage deep learning method, which can achieve the segmentation of lung parenchyma and the classification of CLDs. Compared to previous diagnostic tasks targeting single CLD, this work can achieve various CLDs' diagnosis in the early stage, thereby achieving targeted treatment and increasing the potential and value of clinical applications. [ABSTRACT FROM AUTHOR]

Objectives: Haematopoietic stem cell transplant (HCT) is a cellular therapy that, whilst curative for a child's underlying disease, carries significant risk of mortality, including because of pulmonary complications. The aims of this study were to describe the burden of pulmonary complications post‐HCT in a cohort of Australian children and identify risk factors for the development of these complications. Methods: Patients were identified from the HCT databases at two paediatric transplant centres in Australia. Medical records were reviewed, and demographics, HCT characteristics and pulmonary complications documented. Relative risk ratio was used to identify risk factors for developing pulmonary complications prior to first transplant episode, and survival analysis performed to determine hazard ratio. Results: In total, 243 children underwent transplant during the study period, and pulmonary complications occurred in 48% (117/243) of children. Infectious complications were more common (55%) than non‐infective complications (18%) and 26% of patients developed both. Risk factors for the development of pulmonary complications included the following: diagnoses of MPAL (RR 2.16, P = 0.02), matched unrelated donor (RR1.34, P = 0.03), peripheral blood (RR 1.36, P = 0.028) or cord blood (RR 1.73, P = 0.012) as the stem cell source and pre‐existing lung disease (RR1.72, P < 0.0001). Children with a post‐HCT lung complication had a significantly increased risk of mortality compared with those who did not (HR 3.9, P < 0.0001). Conclusion: This study demonstrates pulmonary complications continue to occur frequently in children post‐HCT and contribute significantly to mortality. Highlighting the need for improved strategies to identify patients at risk pre‐transplant and enhanced treatments for those who develop lung disease. [ABSTRACT FROM AUTHOR]

Objectives: In cystic fibrosis (CF), an imbalanced lipid metabolism is associated with lung inflammation. Little is known about the role that specific lipid mediators (LMs) exert in CF lung inflammation, and whether their levels change during early disease progression. Therefore, we measured airway LM profiles of young CF patients, correlating these with disease‐associated parameters. Methods: Levels of omega (ω)‐3/6 PUFAs and their LM derivatives were determined in bronchoalveolar lavage fluid (BALF) of children with CF ages 1–5 using a targeted high‐performance liquid chromatography–tandem mass spectrometry approach. Hierarchical clustering analysis was performed on relative LM levels. Individual relative LM levels were correlated with neutrophilic inflammation (BALF %Neu) and structural lung damage (PRAGMA‐CF %Disease). Significant correlations were included in a backward multivariate linear regression model to identify the LMs that are best related to disease progression. Results: A total of 65 BALF samples were analysed for ω‐3/6 lipid content. LM profiles clustered into an arachidonic acid (AA)‐enriched and a linoleic acid (LA)‐enriched sample cluster. AA derivatives like 17‐OH‐DH‐HETE, 5‐HETE, 5,15‐diHETE, 15‐HETE, 15‐KETE, LTB4 and 6‐trans‐LTB4 positively correlated with BALF %Neu and/or PRAGMA %Dis. Contrastingly, 9‐HoTrE and the LA derivatives 9‐HoDE, 9(10)‐EpOME, 9(10)‐DiHOME, 13‐HoDE, 13‐oxoODE and 12(13)‐EpOME negatively correlated with BALF %Neu and/or PRAGMA %Dis. 6‐trans‐LTB4 was the strongest predictor for BALF %Neu. 5‐HETE and 15‐KETE contributed most to PRAGMA %Dis prediction. Conclusions: Our data provide more insight into the lung lipidome of infants with CF, and show that a shift from LA derivatives to AA derivatives in BALF associates with early CF lung disease progression. [ABSTRACT FROM AUTHOR]

Diagnosing diffuse infiltrative lung diseases (DILD) using high‐resolution computed tomography (HRCT) is challenging, even for expert radiologists, due to the complex and variable image patterns. Moreover, the imbalances among the six key DILD‐related patterns—normal, ground‐glass opacity, reticular opacity, honeycombing, emphysema, and consolidation—further complicate accurate segmentation and diagnosis. This study presents an enhanced U‐Net‐based segmentation technique aimed at addressing these challenges. The primary contribution of our work is the fine‐tuning of the U‐Net model using image‐level labels from 92 HRCT images that include various types of DILDs, such as cryptogenic organizing pneumonia, usual interstitial pneumonia, and nonspecific interstitial pneumonia. This approach helps to correct the imbalance among image patterns, improving the model's ability to accurately differentiate between them. By employing semantic lung segmentation and patch‐level machine learning, the fine‐tuned model demonstrated improved agreement with radiologists' evaluations compared to conventional methods. This suggests a significant enhancement in both segmentation accuracy and inter‐observer consistency. In conclusion, the fine‐tuned U‐Net model offers a more reliable tool for HRCT image segmentation, making it a valuable imaging biomarker for guiding treatment decisions in patients with DILD. By addressing the issue of pattern imbalances, our model significantly improves the accuracy of DILD diagnosis, which is crucial for effective patient care. [ABSTRACT FROM AUTHOR]

Major histocompatibility complex class I (MHC I) molecules present peptides to CD8+ T‐cells for immunosurveillance of infection and cancer. Recent studies indicate lineage‐specific heterogeneity in MHC I expression. While respiratory diseases rank among the leading causes of mortality, studies in mice have shown that lung epithelial cells (LECs) express the lowest levels of MHC I in the lung. This study aims to answer three questions: (i) Do human LECs express low levels of MHC I? (ii) Is LEC MHC I expression modulated in chronic respiratory diseases? (iii) Which factors regulate MHC I levels in human LECs? We analyzed human LECs from parenchymal explants using single‐cell RNA sequencing and immunostaining. We confirmed low constitutive MHC I expression in human LECs, with significant upregulation in chronic respiratory diseases. We observed a sexual dimorphism, with males having higher MHC I levels under steady‐state conditions, likely due to differential redox balance. Our study unveils the complex interplay between MHC I expression, sex, and respiratory disease. Since MHC I upregulation contributes to the development of immunopathologies in other models, we propose that it may have a similar impact on chronic lung disease. [ABSTRACT FROM AUTHOR]

Background: This field efficacy study was designed to determine the efficacy of a new bivalent vaccine containing porcine circovirus type 2d (PCV2d) and Mycoplasma hyopneumoniae at three independent pig farms. Methods: Three pig farms were selected based on their history of subclinical PCV2 infection and enzootic pneumonia. Each farm housed a total of 40, 18‐day‐old pigs that were randomly allocated to 1 of 2 treatment groups. Pigs were administered a 2.0 mL dose of the bivalent vaccine intramuscularly at 21 days of age in accordance with the manufacturer's recommendations, whereas unvaccinated pigs were administered a single dose of phosphate‐buffered saline at the same age. Results: Clinically, the average daily weight gain of vaccinated groups was significantly higher (p < 0.05) than those of unvaccinated animals during the growing (70–112 days of age), finishing (112–175 days of age) and overall (3–175 days of age) stages of production. Vaccinated animals elicited neutralizing anti‐PCV2 antibodies and PCV2d‐specific interferon‐γ secreting cells (IFN‐γ‐SC), which reduced the amount of PCV2d genomic copies in blood and reduced lymphoid lesions severity when compared with unvaccinated animals. Similarly, vaccinated animals elicited M. hyopneumoniae‐specific IFN‐γ‐SC, which reduced the amount of M. hyopneumoniae in the larynx and reduced lung lesions severity. Conclusions: The result of the field trial demonstrated that the bivalent vaccine was efficacious in the protection of swine herds suffering from subclinical PCV2d infection and enzootic pneumonia. [ABSTRACT FROM AUTHOR]

Sinusoidal obstruction syndrome/veno‐occlusive disease (SOS/VOD) is a life‐threatening complication which can develop after haemopoietic stem cell transplantation (HSCT) and some antibody–drug conjugates. Several SOS/VOD diagnostic and management guidelines exist, with the most recent and refined being the European Society for Blood and Marrow Transplantation adult and paediatric guidelines. Timely diagnosis and effective management (including the availability of therapeutic options) significantly contribute to improved patient outcomes. In Australia and New Zealand, there is variability in clinical practice and access to SOS/VOD therapies. This review aims to summarise the current evidence for SOS/VOD diagnosis, prevention and treatment and to provide recommendations for SOS/VOD in the context of contemporary Australasian HSCT clinical practice. [ABSTRACT FROM AUTHOR]

Background and Objective: Lymphangioleiomyomatosis (LAM) is a rare neoplastic disease associated with the functional tumour suppressor genes TSC1 and TSC2 and causes structural destruction in the lungs, which could potentially increase the risk of lung cancer. However, this relationship remains unclear because of the rarity of the disease. Methods: We investigated the relative risk of developing lung cancer among patients diagnosed with LAM between 2001 and 2022 at a single high‐volume centre in Japan, using data from the Japanese Cancer Registry as the reference population. Next‐generation sequencing (NGS) was performed in cases where tumour samples were available. Results: Among 642 patients diagnosed with LAM (sporadic LAM, n = 557; tuberous sclerosis complex‐LAM, n = 80; unclassified, n = 5), 13 (2.2%) were diagnosed with lung cancer during a median follow‐up period of 5.13 years. All patients were female, 61.5% were never smokers, and the median age at lung cancer diagnosis was 53 years. Eight patients developed lung cancer after LAM diagnosis. The estimated incidence of lung cancer was 301.4 cases per 100,000 person‐years, and the standardized incidence ratio was 13.6 (95% confidence interval, 6.2–21.0; p = 0.0008). Actionable genetic alterations were identified in 38.5% of the patients (EGFR: 3, ALK: 1 and ERBB2: 1). No findings suggested loss of TSC gene function in the two patients analysed by NGS. Conclusion: Our study revealed that patients diagnosed with LAM had a significantly increased risk of lung cancer. Further research is warranted to clarify the carcinogenesis of lung cancer in patients with LAM. [ABSTRACT FROM AUTHOR]

Background and Objective Methods Results Conclusion Sarcoidosis can manifest with atypical findings on chest computed tomography (CT). Cysts are a rare manifestation of lung sarcoidosis. The aim of the study was to describe a series of patients with cystic sarcoidosis and their clinical‐radiological characteristics and progression.In this retrospective, bicentric study we recruited all patients affected by sarcoidosis with lung cystic lesions at chest CT. We collected clinical characteristics, pulmonary tests and tracked number, distribution and size of the cysts at diagnosis and at the last evaluation.Twelve patients (6 males, median age 53 years) were identified (prevalence: 1.9%; 95% Confidence Interval: 0.8%–2.9%). All patients presented multiple cystic lesions (median number: 14 [range: 2–216]) with a bilateral distribution in 10/12, micronodules and nodules in 11/12 and fibrotic lesions in 4/12. Seven patients had normal lung function test, three had an obstructive syndrome, one had a restrictive syndrome and one had coexistence of both. During follow‐up (median: 10 years [range 1–16 years]), an increase of the number of cysts was observed in four patients. At last evaluation, 3/12 patients experienced a decline of forced vital capacity >10% and 3/12 patients a decline of diffusing capacity for carbon monoxide (DLCO) >10%. A lower DLCO at diagnosis, and the presence of nodules or fibrotic lesions on CT were associated with an increase in the number of cysts.Cystic lung lesions are rare in patients with sarcoidosis and do not influence long term prognosis. [ABSTRACT FROM AUTHOR]

Summary The objective of this study is to assess obesity prevalence and characterize European nursing home (NH) residents with obesity comprehensively. Cross‐sectional nutritionDay data from 2016 to 2021. Descriptive characterization of European NH residents ≥65 years with and without obesity. Binomial logistic regression to identify factors associated with obesity. A total of 11 327 residents (73.8% female, 86.4 ± 7.9 years, mean body mass index 25.3 ± 5.4 kg/m2) from 12 countries were analysed. Obesity prevalence was 17.7%, mostly class I (13.0%). Taking ≥5 drugs/day (OR 1.633; 95% confidence intervals 1.358–1.972), female sex (1.591; 1.385–1.832), being bed/chair‐bound (1.357; 1.146–1.606), and having heart/circulation/lung disease (1.276; 1.124–1.448) was associated with increased obesity risk, older age (0.951; 0.944–0.958), mild (0.696; 0.601–0.805) and severe (0.591; 0.488–0.715) dementia, eating less than ¾ of lunch on nutritionDay (0.669; 0.563–0.793), needing assistance for eating (0.686; 0.569–0.825), and being identified by NH staff at risk for (0.312; 0.255–0.380) or with malnutrition (0.392; 0.236–0.619) decreased obesity risk. Almost one in five residents in European NH participating in nutritionDay is affected by obesity. Through a wide exploratory analysis, including data from 12 European countries, we confirmed previous findings and identified additional factors associated with obesity that should be considered in the daily care of affected residents. [ABSTRACT FROM AUTHOR]

Objective: The ORAL Surveillance trial found a dose‐dependent increase in venous thromboembolism (VTE) and pulmonary embolism (PE) events with tofacitinib versus tumor necrosis factor inhibitors (TNFi). We aimed to assess VTE incidence over time and explore risk factors of VTE, including disease activity, in ORAL Surveillance. Methods: Patients with rheumatoid arthritis (RA) aged 50 years or older with at least one additional cardiovascular risk factor received tofacitinib 5 or 10 mg twice daily (BID) or TNFi. Post hoc, cumulative probabilities and incidence rates (patients with first events/100 patient‐years) by 6‐month intervals were estimated for adjudicated VTE, deep vein thrombosis, and PE. Cox regression models identified risk factors. Clinical Disease Activity Index leading up to the event was explored in patients with VTE. Results: Cumulative probabilities for VTE and PE were higher with tofacitinib 10 mg BID, but not 5 mg BID, versus TNFi. Incidence rates were consistent across 6‐month intervals within treatments. Across treatments, risk factors for VTE included prior VTE, body mass index greater than or equal to 35 kg/m2, older age, and history of chronic lung disease. At the time of the event, most patients with VTE had active disease as defined by Clinical Disease Activity Index. Conclusion: Incidences of VTE and PE were higher with tofacitinib (10 > 5 mg BID) versus TNFi and were generally consistent over time. Across treatments, VTE risk factors were aligned with previous studies in the general RA population. These data highlight the importance of assessing VTE risk factors, including age, body mass index, and VTE history, when considering initiation of tofacitinib or TNFi in patients with active RA. [ABSTRACT FROM AUTHOR]

Background: Helicobacter pylori (H. pylori) infection is currently widespread throughout the world. Bismuth‐containing quadruple therapy is widely used, but it has rarely been associated with interstitial lung disease. Case Presentation: We described six cases with similar clinical symptoms and typical pulmonary interstitial imaging changes during anti‐H. pylori therapy, usually on Days 7–12 following treatment. Anti‐H. pylori infection treatment was discontinued when it was suspected to be the cause of the clinical symptoms, and all of the patients accepted observation therapy. All of them had a favorable outcome, the clinical symptoms returned to normal almost 1 week later, and the chest computed tomography (CT) scan images showed remarkable absorption 4 weeks later. Conclusions: Drug interactions could be the cause, and the most likely drug was furazolidone. All of the patients recovered quickly after drug discontinuation, and low‐dose steroid may help shorten the recovery time. [ABSTRACT FROM AUTHOR]

Summary: Late toxicities can impact survivorship in patients with classical Hodgkin lymphoma (cHL) with pulmonary toxicity after bleomycin‐containing chemotherapy being a concern. The incidence of pulmonary diseases was examined in this Danish population‐based study. A total of 1474 adult patients with cHL treated with ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) or BEACOPP (bleomycin, vincristine, etoposide, doxorubicin, cyclophosphamide, procarbazine and prednisone) between 2000 and 2018 were included along with 7370 age‐ and sex‐matched comparators from the background population. Median follow‐up was 8.6 years for the patients. Patients with cHL had increased risk of incident pulmonary diseases (HR 2.91 [95% CI 2.30–3.68]), with a 10‐year cumulative risk of 7.4% versus 2.9% for comparators. Excess risks were observed for interstitial lung diseases (HR 15.84 [95% CI 9.35–26.84]) and chronic obstructive pulmonary disease (HR 1.99 [95% CI 1.43–2.76]), with a 10‐year cumulative risk of 4.1% and 3.5% respectively for patients. No excess risk was observed for asthma (HR 0.82 [95% CI 0.43–1.56]). Risk factors for interstitial lung diseases were age ≥60 years, the presence of B‐symptoms and low albumin. These findings document a significant burden of pulmonary diseases among patients with cHL and emphasize the importance of diagnostic work‐up of pulmonary symptoms. [ABSTRACT FROM AUTHOR]

Noninvasive and effective methods for early screening of non‐small cell lung cancer (NSCLC) still need to be developed. At present, a reasonable conclusion is that a combination of tumor markers is a superior predictor of screening. Cytokines, as important regulators of cancer development, have great potential for the screening and prognosis of NSCLC. This study screened novel biomarkers related to the early screening and prognosis of NSCLC. In the present study, the biological significance and immunoregulation of interleukin‐24 (IL‐24) were analyzed based on The Cancer Genome Atlas data. Next, 150 serum samples from initially treated patients with NSCLC and 70 controls were collected, and we obtained pathological sections from 60 patients with NSCLC. The ELISA and immunohistochemistry results showed the differential expression of IL‐24 and carbohydrate antigen 125 (CA125). The results show that IL‐24 is an important tumor suppressor in NSCLC that helps to improve the poor prognosis of these patients. A significantly negative correlation between IL‐24 and CA125 levels was also found. Notably, serum IL‐24 levels were significantly negatively correlated with the TNM stage of patients with NSCLC, consistent with an important role for tumor suppressors in NSCLC. The receiver operating characteristic curve analysis showed that a combination of IL‐24 and CA125 was an effective panel for discriminating patients with NSCLC from HD, and individuals with other lung diseases. Serum IL‐24 and CA125 levels were identified as independent prognostic markers for NSCLC. The IL‐24 and CA125 panel exhibited good performance in the screening of NSCLC. [ABSTRACT FROM AUTHOR]

Key Clinical Message: A 46‐year‐old male developed respiratory distress due to asthma‐chronic obstructive pulmonary disease overlap and experienced severe tremor caused by beta2 agonist inhalant. We present our successful experience with tizanidine administration. [ABSTRACT FROM AUTHOR]

Background: The inhalation of paraquat (PQ), one of the most widely used herbicides in the world, can result in lung injury. Curcuma longa (Cl) has long history in traditional and folk medicine for the treatment of a wide range of disorders including respiratory diseases. Aim: The aim of the present work was to evaluate the preventive effect of Cl on inhaled PQ‐induced lung injury in rats. Methods: Male Wistar rats were divided into 8 groups (n = 7), one group exposed to saline (control) and other groups exposed to PQ aerosol. Saline (PQ), Cl extract, (two doses), curcumin (Cu), pioglitazone (Pio), and the combination of Cl‐L + Pio and dexamethasone (Dex) were administered during the exposure period to PQ. Total and differential white blood cell (WBC) counts, oxidant and antioxidant indicators in the bronchoalveolar lavage (BALF), interleukin (IL)‐10, and tumor necrosis alpha (TNF‐α) levels in the lung tissues, lung histologic lesions score, and air way responsiveness to methacholine were evaluated. Results: WBC counts (Total and differential), malondialdehyde level, tracheal responsiveness (TR), IL‐10, TNF‐α and histopathological changes of the lung were markedly elevated but total thiol content and the activities of catalase and superoxide dismutase were decreased in the BALF in the PQ group. Both doses of Cl, Cu, Pio, Cl‐L + Pio, and Dex markedly improved all measured variables in comparison with the PQ group. Conclusion: CI, Pio, and Cl‐L + Pio improved PQ‐induced lung inflammation and oxidative damage comparable with the effects of Dex. [ABSTRACT FROM AUTHOR]

Introduction: Direct current cardioversion (DCCV) remains one of the recommended management strategies for symptomatic atrial fibrillation (AF). Antiarrhythmic drugs (AAD) are prescribed post procedure to maintain sinus rhythm (SR). Limited literature exists on the AAD prescribing practices and their efficacy, post‐DCCV in rural Australia. Objective: The primary aim was to determine the preferred AAD post‐DCCV and the factors affecting AAD prescribing practices. The secondary aim was to assess the efficacy of the AAD in maintaining SR. Design: A retrospective observational audit of patients with non‐valvular AF who underwent successful elective DCCV for symptomatic AF, during 2015–2020 at a regional hospital in New South Wales (NSW) (Dubbo Base Hospital). Patients were followed up for a duration of 12 months post‐DCCV. Results: 233 patients underwent successful DCCV during the study duration. Amiodarone was the preferred AAD of choice post‐DCCV followed by sotalol and flecainide, respectively (36.5% vs. 27.8% vs. 1.3%). 35.2% patients were not prescribed AAD. Amiodarone and sotalol had similar but modest efficacies and neither were superior to no AAD, in maintaining SR 12 months post‐DCCV (AF recurrence rate 61.5% vs. 68.2% vs. 71.6% respectively, p = 0.37). Antecedent cerebrovascular accident (CVA), pulmonary disease, smoking, prior treatment with digoxin, diuretics and left ventricular (LV) dysfunction were factors that influenced AAD prescribing practices. Conclusion: The study demonstrates equal efficacies of amiodarone, sotalol and no AAD in maintaining SR 12 months post‐DCCV. Prescribing practices post‐DCCV at Dubbo Base Hospital differ from observed national trends and guidelines. AAD prescription requires a multifaceted approach with a key consideration to prioritise safety over efficacy, being mindful of challenges in delivering optimal healthcare in a rural setting. [ABSTRACT FROM AUTHOR]

Diagnosis and treatment of pulmonary hypertension (PH) in patients with lung diseases (PH‐LD) remain unestablished and pose significant challenges. In this report, we present a case of a 77‐year‐old patient with an indeterminate for usual interstitial pneumonia pattern along with chronic obstructive pulmonary disease, who developed groups 1 and 3 PH. Following diagnosis, upfront triple oral combination therapy (UTOCT) with macitentan, sildenafil, and selexipag was initiated. Stability in disease progression was achieved over 4 years with the addition of pirfenidone to address interstitial lung disease progression. To the best of our knowledge, this represents the first reported case of PH‐LD, where disease control was maintained with the addition of pirfenidone to UTOCT. This case suggests that some patients with PH‐LD, presenting with groups 1 and 3 PH, may benefit from combined UTOCT and antifibrotic agents, potentially improving symptoms and extending their prognosis. [ABSTRACT FROM AUTHOR]

One of the resistant mechanisms of EGFR‐TKIs is BRAF V600E mutation. Herein, we present the case of a 54‐year‐old Japanese female who underwent a right middle lobectomy for pathological stage IIB lung adenocarcinoma. One year and nine months after the surgery, she developed multiple intrapulmonary metastases. Osimertinib was administered due to EGFR exon 19 deletion. Although all intrapulmonary metastases had shrunk, the nodule at the superior segment of left lung enlarged after postoperative 4 years. The tumour was resected and BRAF V600E mutation and exon 19 deletion were detected. Three months after treatment with dabrafenib and trametinib instead of osimertinib, the remaining intrapulmonary metastases increased again. The continued growth of the metastatic foci even after EGFR‐TKI may indicate an acquired resistance. Thus, a repeat biopsy will aid in confirming the new gene expression. It should have been necessary to administer an additional dose of dabrafenib and trametinib without discontinuing osimertinib. [ABSTRACT FROM AUTHOR]

Background and main body: Although interactions between the nervous and immune systems have been recognized decades ago, it has become increasingly appreciated that neuroimmune crosstalk is among the driving factors of multiple pulmonary inflammatory diseases including acute lung injury (ALI). Here, we review the current understanding of nerve innervations towards the lung and summarize how the neural regulation of immunity and inflammation participates in the onset and progression of several lung diseases, especially ALI. We then present advancements in the development of potential drugs for ALI targeting neuroimmune interactions, including cholinergic anti‐inflammatory pathway, sympathetic‐immune pathway, purinergic signalling, neuropeptides and renin‐angiotensin system at different stages from preclinical investigation to clinical trials, including the traditional Chinese medicine. Conclusion: This review highlights the importance of considering the therapeutic strategy of inflammatory diseases within a conceptual framework that integrates classical inflammatory cascade and neuroimmune circuits, so as to deepen the understanding of immune modulation and develop more sophisticated approaches to treat lung diseases represented by ALI. Key points: The lungs present abundant nerve innervations.Neuroimmune interactions exert a modulatory effect in the onset and progression of lung inflammatory diseases, especially acute lung injury.The advancements of potential drugs for ALI targeting neuroimmune crosstalk at different stages from preclinical investigation to clinical trials are elaborated.Point out the direction for the development of neuroimmune pharmacology in the future. [ABSTRACT FROM AUTHOR]

The interactions between immune cells and epithelial cells influence the progression of many respiratory diseases, such as chronic obstructive pulmonary disease (COPD). In vitro models allow for the examination of cells in controlled environments. However, these models lack the complex 3D architecture and vast multicellular interactions between the lung resident cells and infiltrating immune cells that can mediate cellular response to insults. In this study, three complementary microphysiological systems are presented to delineate the effects of cigarette smoke and respiratory disease on the lung epithelium. First, the Transwell system allows the co‐culture of pulmonary immune and epithelial cells to evaluate cellular and monolayer phenotypic changes in response to cigarette smoke exposure. Next, the human and mouse precision‐cut lung slices system provides a physiologically relevant model to study the effects of chronic insults like cigarette smoke with the dissection of specific interaction of immune cell subtypes within the structurally complex tissue environment. Finally, the lung‐on‐a‐chip model provides an adaptable system for live imaging of polarized epithelial tissues that mimic the in vivo environment of the airways. Using a combination of these models, a complementary approach is provided to better address the intricate mechanisms of lung disease. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusions Chest computed tomography (CT) scan is useful to evaluate the type and extent of lung lesions in coronavirus disease 2019 (COVID‐19) pneumonia. This study explored the association between radiological parameters and various circulating serum‐derived markers, including microRNAs, in older patients with COVID‐19 pneumonia.A retrospective analysis was designed to study geriatric patients (≥75 years) with COVID‐19 pneumonia, who underwent chest CT scan on admission, and for whom clinical data and serum samples were obtained. To quantify the extent of lung involvement, CT‐score, the percentage of healthy lung (HL%), the percentage of ground glass opacity (GGO%), and the percentage of lung consolidation were assessed using computer‐aided tools. The association of these parameters with two circulating microRNAs, miR‐483‐5p and miR‐320b, previously identified as biomarkers of mortality risk in COVID‐19 geriatric patients, was tested.A total of 73 patients with COVID‐19 pneumonia were evaluable (median age 85 years; interquartile range 82–90 years). Among chest CT‐derived parameters, the percentage of lung consolidation (HR 1.08, 95% CI 1.02–1.14), CT‐score (HR 1.14, 95% CI 1.03–1.25), and HL% (HR 0.97, 95% CI 0.95–0.99) emerged as significant predictors of mortality, whereas non‐significant trends toward increased mortality were observed in patients with higher GGO%. We also found a significant positive association between serum miR‐483‐5p and GGO% (correlation coefficient 0.28; P = 0.018) and a negative association with HL% (correlation coefficient −0.27; P = 0.023).Overall, the extent of lung consolidation can be confirmed as a prognostic parameter of COVID‐19 pneumonia in older patients. Among various serum‐derived markers, miR‐483‐5p can help in exploring the degree of lung involvement, due to its association with higher GGO% and lower HL%. Geriatr Gerontol Int 2024; ••: ••–••. [ABSTRACT FROM AUTHOR]

Mitochondria are dynamic organelles that continuously undergo fusion/fission to maintain normal cell physiological activities and energy metabolism. When mitochondrial dynamics is unbalanced, mitochondrial homeostasis is broken, thus damaging mitochondrial function. Accumulating evidence demonstrates that impairment in mitochondrial dynamics leads to lung tissue injury and pulmonary disease progression in a variety of disease models, including inflammatory responses, apoptosis, and barrier breakdown, and that the role of mitochondrial dynamics varies among pulmonary diseases. These findings suggest that modulation of mitochondrial dynamics may be considered as a valid therapeutic strategy in pulmonary diseases. In this review, we discuss the current evidence on the role of mitochondrial dynamics in pulmonary diseases, with a particular focus on its underlying mechanisms in the development of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), asthma, pulmonary fibrosis (PF), pulmonary arterial hypertension (PAH), lung cancer and bronchopulmonary dysplasia (BPD), and outline effective drugs targeting mitochondrial dynamics‐related proteins, highlighting the great potential of targeting mitochondrial dynamics in the treatment of pulmonary disease. [ABSTRACT FROM AUTHOR]