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Introduction: The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to pose major health challenges despite effective vaccination efforts. The sustained occurrence of breakthrough infections and emerging variants of the virus highlights the need for additional therapeutic strategies. Given the anti-inflammatory role of the cannabinoid type 2 receptor (CB2R), we examined the effect of CB2R activation in SARS-CoV-2 spike protein subunit 1 (S1SP)-induced acute lung injury (ALI).

Methods: ALI was induced in mice by intratracheal (i.t.) administration of S1SP, followed by treatment with the CB2R agonist HU308 (5 mg/kg, intraperitoneal: i.p.) 1 h post-S1SP and every 24 h thereafter. Lung function, bronchoalveolar lavage fluid (BALF) parameters, cytokine levels, and inflammatory signaling were assessed at 48 h following S1SP exposure.

Results: HU308 treatment significantly reduced S1SP-induced pulmonary dysfunction, immune cell infiltration, neutrophil activation, and proinflammatory cytokine production, while suppressing NF-κB and STAT3 activation. HU308 treatment restored the Nrf2 expression in the lung.

Conclusion: CB2R activation ameliorates S1SP-induced lung inflammation and injury, suggesting its therapeutic potential against COVID-19-related ALI.

Purpose: E-cigarette use, or vaping, is increasing in prevalence, especially among adolescents. There is a paucity of information on the impact of e-cigarette aerosols on lung health, particularly to the airway protective components. In this study, disruptions to airway protective functions in response to increasing repetitive exposure to nicotine-free e-cigarette aerosols were examined. The recovery capability of the airway defence was also investigated.

Methods: Cultured primary nasal airway cells from five healthy individuals were exposed to repetitive exposures to e-cigarette aerosols. Cilia function was analysed via high-speed video microscopy, while epithelial barrier integrity was assessed through trans-epithelial electrical resistance measurements and immunofluorescence. Cytokine secretion was assessed using multiplex screening.

Results: Significant impairment in cilia function and epithelial barrier integrity was observed after 24 or more vaping exposures. Cilia beating frequency declined by 18.6% (6.78 ± 0.23 Hz) after 24 sessions and by 53.0% (3.91 ± 0.27 Hz) after 60 sessions (p < 0.01). Trans-epithelial electrical resistance values dropped by 45.6% (315.37 ± 13.38 Ωcm²) after 24 sessions and by 77.4% (131.29 ± 6.84 Ωcm²) after 60 sessions (p < 0.01). Nicotine-free aerosols disrupted Occludin-1 and ZO-1 expression but not E-cadherin. Cytokine analysis showed increased secretion of IL-1ra, IL-6, FGF-basic, IFN-γ, and VEGF following 36 vaping sessions. Recovery experiments indicated cilia function normalised within 48 h, while epithelial barrier required up to 72 h.

Conclusion: Repetitive vaping progressively impairs airway protective functions in vitro. While cilia function and epithelial integrity recover in the short term, the delay may increase susceptibility to infections.

Introduction: Primary ciliary dyskinesia (PCD) is a rare, congenital condition in which impaired ciliary function leads to bronchiectasis and progressive lung function decline. Bronchiectasis development is believed to involve infection and inflammation but is incompletely understood. Macrophages play a central role in cellular immune response, contributing to both pathogen clearance and immunoregulation. Depending on local stimuli, macrophages are polarized towards pro-inflammatory (M1) or pro-resolution/phagocytic (M2) phenotypes. This study aims to investigate the effects of PCD sputum on macrophage polarization.

Methods: Sputum from 27 individuals with PCD and seven healthy controls were used to stimulate healthy monocyte-derived macrophages. Macrophage polarization was determined by surface markers, phagocytic ability and cytokine production using flow cytometry and immunoassays.

Results: Macrophages stimulated with PCD sputum exhibited enhanced phagocytosis (MFI 194268 vs. 58235, p = 0.0002), increased expression of M2-associated surface markers CD163, CD206 and CD16, and reduced secretion of proinflammatory cytokines IL-6 (10.38 vs. 113.22 pg/ml, p = 0.0013) and IL-1β (0.75 vs. 3.60 pg/ml, p < 0.0001). Concurrently, expressions of M1-associated surface markers CD40 and CD80 were reduced.

Conclusion: PCD sputum induced a phagocytosis prone, M2-like phenotype in healthy macrophages.

Purpose: To assess whether a Network Physiology approach using Sample Entropy and Transfer Entropy can be applied to simple physiological signals obtained during sleep studies, to accurately distinguish between different types of sleep disordered breathing (SDB) and streamline the diagnostic process.

Methods: Retrospective study on patients who underwent a sleep study between January 2017 and December 2021. The training dataset, used for algorithm development, included four clinically important groups: normal, obstructive sleep apnoea alone, sustained nocturnal hypoxemia with a high AHI (≥ 30/hr) and sustained nocturnal hypoxemia with a low AHI (< 30/hr). Mean, standard deviation, Sample Entropy and Transfer Entropy was calculated for heart rate, respiratory rate, oxygen saturation and nasal flow for each patient. Sample entropy is a measure of signal complexity. This was validated in a separate test dataset. ROC analysis was used.

Results: In the training dataset (n = 105), the Sample Entropy of the oxygen saturation signal was significantly different in patients with SDB compared to normal studies. The area under a ROC curve for predicting obstructive sleep apnoea from normal studies and sustained hypoxia with a high AHI (≥ 30events/hr) compared to sustained hypoxia with a low AHI (AHI < 30events/hr) was 0.943 and 0.785 respectively. When tested in the test dataset (n = 80), oxygen saturation Sample Entropy above 0.1456 was 100% sensitive and 60% specific in diagnosing obstructive sleep apnoea. Patients with OSA had significantly increased Transfer Entropy from HR → SpO2, RR → SpO2 and NF → SpO2; and significantly decreased Transfer Entropy from SpO2 → RR.

Interpretation: Network Physiology mapping of oxygen saturation can help distinguish between different types of sleep disordered breathing and has the potential to support simplified global diagnostic pathways for sleep apnoea utilising oximetry alone.

Background: Bronchopulmonary dysplasia (BPD) remains a significant complication in very preterm infants (< 32 weeks gestational age). Risk factors may differ between mild and moderate-to-severe BPD, but stratified analyses are limited.

Objective: To compare risk factors for mild versus moderate-to-severe BPD in very preterm infants (< 32 weeks gestational age).

Methods: This retrospective study analyzed data from very preterm infants (< 32 weeks gestational age) admitted to a tertiary neonatal intensive care unit between January 2017 and December 2024. BPD was classified as mild, moderate, or severe according to the 2001 NICHD/NHLBI criteria. Maternal, perinatal, and postnatal variables were compared between no-BPD, mild BPD, and moderate-to-severe BPD groups.

Results: Among 486 very preterm infants (< 32 weeks gestational age), 213 (43.8%) had no BPD, 147 (30.2%) had mild BPD, and 126 (25.9%) had moderate-to-severe BPD. After multivariate analysis, lower gestational age (aOR 1.92, 95% CI 1.63-2.26), male sex (aOR 1.68, 95% CI 1.14-2.48), and prolonged mechanical ventilation (aOR 1.21, 95% CI 1.14-1.29) were risk factors for both mild and moderate-to-severe BPD. However, histological chorioamnionitis (aOR 2.35, 95% CI 1.54-3.59), pulmonary hypertension (aOR 3.12, 95% CI 1.87-5.21), and postnatal sepsis (aOR 2.15, 95% CI 1.43-3.24) were significantly associated only with moderate-to-severe BPD.

Conclusion: Risk factors for BPD in very preterm infants (< 32 weeks gestational age) differ by disease severity. Identifying severity-specific risk factors may help develop targeted prevention strategies and improve outcomes.

Introduction: The frequent-exacerbator (FE) phenotype guides COPD management, yet its year-to-year stability and the role of airway eosinophilia in FE remission are uncertain.

Methods: In a single-center prospective cohort (n = 289), patients were classified as FE (≥ 2 moderate or ≥ 1 severe exacerbation in the prior year; n = 88) or non-FE (n = 201) and followed 12 months. FE patients were labeled FE-persistent or FE-remitted at 1 year. Clinical data, spirometry, CT, fractional exhaled nitric oxide (FeNO), blood counts, and induced-sputum cytology were collected. Logistic regression identified correlates of remission; ROC/AUC with bootstrap validation and calibration assessed models.

Results: FE prevalence was 30.4%; 58.0% of FE patients remitted. Compared with non-FE, FE had higher SE% and more eosinophilic/mixed sputum phenotypes. Within FE, remitters had better lung function and greater airway eosinophilia. Each 1% SE% increase independently predicted remission (OR 1.21, 95% CI 1.03-1.47); SE% ≥ 3% tripled the odds (OR 3.76, 95% CI 1.29-11.91). Prior severe exacerbations and CT-defined chronic bronchitis predicted persistence (ORs 0.21-0.27). Models showed good discrimination (AUC 0.785-0.799; bootstrap-corrected 0.750-0.773) and calibration (Brier 0.179).

Conclusion: FE status is dynamic; over half remit within a year. Airway eosinophilia-especially SE% ≥ 3%-independently associates with FE remission, while prior severe exacerbations and CT-chronic bronchitis indicate persistence. Incorporating sputum cytology with history and imaging may enable earlier re-stratification and treatable-trait-guided COPD care.

Purpose: The expiratory time constant (TC), reflecting the rate of lung emptying, has emerged as a marker of early small airway disease. Although TC is traditionally used in mechanical ventilation, several calculation methods are also applicable to spirometry. This study aimed to evaluate the feasibility of four spirometry-based approaches for determining TC and to compare their sensitivity to detect airway obstruction.

Methods: In this multicenter, cross-sectional study of 17,988 adult flow/volume curves, the TC was directly measured (TC_M: time to exhale 63% of forced vital capacity), calculated as proposed by Ikeda (TC_I) and Brunner (TC_B), or derived using the slicing method (TC_S). Stability was assessed by the 5th (lower limit of normal, LLN) and 95th (upper limit of normal, ULN) percentile ranges. Diagnostic performance to detect obstruction was quantified by the area under the receiver operating characteristic curve (AUC).

Results: All four TC methods were feasible but not interchangeable across spirometric categories. In the normal group, TC_I (ULN at 0.7s) and TC_B (ULN at 0.76) were most stable and had values below or at the 0.76s obstruction threshold. In the obstruction group, only TC_M was most closely aligned with the obstruction cutoff (TC_M LLN 0.75s). AUC analysis showed the TC_M was most sensitive (AUC = 0.977) for detecting obstruction, outperforming TC_I (AUC = 0.965), TC_S (AUC = 0.890), and TC_B (AUC = 0.822) (DeLong's test, p < 0.001 for all comparisons). This finding was most pronounced in younger individuals.

Conclusions: TC_M demonstrated the highest overall accuracy for detecting obstruction.

Background: Shape-sensing robotic-assisted bronchoscopy (ssRAB) combined with intraoperative imaging optimizes tool-lesion relationship during the sampling of focal pulmonary lesions. Nevertheless, confirmation of tool-in-lesion status is not equivalent to diagnostic sampling. This gap may be bridged by the addition of transbronchial cryobiopsy (TBCB) to traditional transbronchial needle aspiration (TBNA) and forceps biopsy (TBFB); however, the performance of TBCB, specifically with the 1.7-mm cryoprobe, has raised significant safety concerns.

Objective: Evaluate the safety of TBCB using the 1.7-mm cryoprobe, added into ssRAB-guided TBNA and TBFB, and performed via a protocolized approach in a cancer center patient population undergoing lung biopsy for focal parenchymal pulmonary lesions. Secondary endpoints included diagnostic yield, accuracy, and TBFB vs. TBCB tissue quality measures.

Methods: This prospective, single center, single arm study, enrolled patients referred for sampling of focal pulmonary parenchymal lesions. All procedures were performed with image-guided ssRAB with prophylactic balloon occlusion. The primary endpoint was a safety composite of grade ≥ 2 bleeding, grade ≥ 2 pneumothorax, or other biopsy-related grade ≥ 3 complication. Secondary endpoints included conservative diagnostic yield, diagnostic accuracy for malignancy, and biopsy specimen quality measures.

Results: Fifty-one participants were enrolled and underwent image-guided ssRAB. The primary severe adverse event rate was 0% (95% CI 0.0-7.9). The conservative diagnostic yield was 92% and the diagnostic accuracy for malignancy was 90%. TBCB was superior to forceps biopsy in measures of total specimen dimensions, diagnostic tissue area, and degree of crush artifact (P < 0.001 for all comparisons).

Conclusion: In cancer patients with localized parenchymal lung lesions, the incorporation of a rigorous safety protocol into image-guided ssRAB allows for the safe acquisition of high-quality peripheral lung TBCB specimen, utilizing the 1.7-mm cryoprobe.

Clinical trial registration: Clinicaltrials.gov identifier: NCT04548830.

Asthma is a heterogeneous condition characterized by chronic airway inflammation, airway hyperresponsiveness, and mucin hypersecretion. Obesity-related asthma is one phenotype of asthma with significant metabolic dysregulation. A complete understanding of obesity-related asthma remains elusive, but it is most often characterized by the absence of hallmark features of Type-2 (T2) high asthma, such as eosinophilia or elevated exhaled nitric oxide (NO) levels. Patients with obesity-related and T2 low asthma with or without type 2 diabetes mellitus (T2DM) experience worse clinical outcomes, including more severe acute exacerbations. Among the Food and Drug Administration (FDA) approved drug classes for T2DM, there is a growing interest in glucagon-like peptide 1 receptor agonists' (GLP-1RAs) ability to potentially exert effects in the airway. Previous studies found that individuals with T2DM and asthma who were prescribed GLP-1RAs, had decreased asthma exacerbations and improved lung function. However, there remains a gap in understanding GLP-1RAs mechanism of action in the lung and airways to improve pulmonary function. In this review we discuss the potential mechanisms by which GLP-1RAs may impact T2 low asthma and offer a therapeutic option for this highly prevalent disorder.

Right ventricular failure (RVF) is a complex clinical syndrome resulting from anatomical and physiological dysfunction of the right ventricle, marked by insufficient cardiac output state, elevated filling pressures, and elevated central venous pressures. Historically, acute RVF in the medical intensive care unit (MICU) has posed significant diagnostic and therapeutic challenges, often leading to poor patient outcomes and increased healthcare utilization. RVF is a pervasive and critically underdiagnosed condition in MICUs, often masked by nonspecific symptoms and overlooked in favor of left-sided pathology, despite its profound impact on patient outcomes and mortality. This difficulty stems from a limited understanding of its underlying mechanisms and a lack of high-quality evidence to guide management in critical care settings. Effective care for RVF demands early recognition, precise identification of the underlying etiology, and prompt, targeted interventions. Intensivists must possess comprehensive knowledge and a diverse skill set to navigate these complexities and address unforeseen complications. Over the past two decades, advancements in diagnostic and therapeutic technologies have transformed the approach to RVF, driving significant progress in the field. This review explores the historical evolution, pathophysiology, clinical presentation, and contemporary management strategies for RVF in the MICU.