Search

Introduction: Expiratory central airway collapse is defined by excessive inward bulging of either tracheobronchial posterior membrane or cartilage. The former is called excessive dynamic airway collapse (EDAC), and the latter, depending on the site of collapse, tracheomalacia, bronchomalacia or tracheobronchomalacia. Due to their non-specific symptoms and lack of awareness amongst clinicians they tend to be mislabeled as common obstructive lung disorders, or complicate their course undetected. Particular controversies refer to EDAC sometimes considered just as a symptom of obstructive lung disease and not a separate entity. Nonetheless, a growing body of evidence indicates that EDAC might be present in patients without apparent obstructive lung disease or it might be an independent risk factor in chronic obstructive pulmonary disease or asthma patients., Patient Concerns: Patient #1 was admitted because of idiopathic chronic cough whereas patient #2 was admitted for differential diagnosis of dyspnea of uncertain etiology. In both patients symptoms were unresponsive to bronchodilators and inhaled corticosteroids., Findings and Diagnosis: In both patients an excess collapse of tracheobronchial posterior membrane was detected during bronchoscopy; in patient #1, of right main bronchus and right upper lobe bronchus and in patient #2 of right upper lobe bronchus and both main bronchi. Excess central airway collapse in patient #2 was also visualized on expiratory chest CT. In patient #1 spirometry did not reveal obturation, whereas in patient #2 only mild, irreversible, obstruction was revealed, disproportionate to patients significant breathlessness., Interventions: Both patients were treated with N-acetylcysteine and adjustable positive expiratory pressure valves., Outcomes: Due to aforementioned treatment chronic cough in patient #1 subsided almost completely whereas patient's #2 dyspnea improved significantly., Conclusions: In presented cases EDAC was an unexpected finding, even though, it firmly corresponded with reported symptoms. Treatment modification led to improvement of patients quality of life.

This study aimed to assess the utility of serum YKL-40 and serum dipeptidyl peptidase IV (DPP4) as biomarkers for distinguishing between type 2 (T2)-high and T2-low asthma in the Chinese population. Additionally, we sought to explore the associations of serum YKL-40 and DPP4 levels with asthma characteristics and conventional markers. A real-world observational cross-sectional study was conducted, involving a total of 75 adult asthma patients. We collected general information, including demographics and medical history. Measurements included complete blood count, fractional exhaled nitric oxide (FeNO), post-bronchodilator spirometry, serum YKL-40 and serum DPP4 levels. Asthma endotypes, T2-high and T2-low, were defined through a comprehensive review of existing literature and expert group discussions. Logistic and linear regression models were employed. Our findings indicated no significant association between serum YKL-40 or serum DPP4 levels and T2-high asthma across all models. In the fully adjusted model, their odds ratios (OR) were 0.967 (95% CI: 0.920-1.017) and 0.997 (95% CI: 0.993-1.001), respectively. Notably, serum YKL-40 exhibited a positive correlation with FeNO (β = 0.382, 95% CI: 0.230-0.533) after adjusting for confounding factors. This association, however, diminished in patients under 40 years old (P = .24), males (P = .25), and those with FEV1%pred of 80% or higher (P = .25). Serum DPP4 demonstrated a negative correlation with FEV1/FVC in the fully adjusted model (β: -0.005, 95% CI: -0.009, -0.000). Among Chinese adult asthma patients, a positive correlation was observed between serum YKL-40 levels and FeNO in females aged over 40 with FEV1%pred less than 80%. Additionally, a weak negative correlation was found between serum DPP4 levels and FEV1/FVC. However, neither serum YKL-40 nor serum DPP4 levels exhibited the capability to differentiate between T2-high and T2-low asthma., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose of Review: Systemic opioids have the evidence to support their use in refractory dyspnea; however, the mechanisms of how they exert their effects are not fully understood. The relevance of peripheral mechanisms, in part, is still questioned, especially as a meta-analysis demonstrated no benefit from nebulized opioids. This might be related to the lack of standardization of the inhalation methods. There is a need to clarify whether peripheral opioid receptors may serve as the target for inhaled treatment and what are the potential peripheral mechanisms of opioids., Recent Findings: Opioidergic systems are present in structures important for the regulation of bronchial and pulmonary vascular responses, as well as breathlessness perception in the human respiratory system. Opioid receptors located in the pulmonary neuroendocrine cells (PNECs) and sensory C-fibers within the bronchial epithelium are easily accessible for inhaled treatment. Morphine administrated by a pneumodosimetric method shows a different pharmacokinetic profile to those described for systemic routes, suggesting local metabolism in lung., Summary: Research suggests that peripheral opioid receptors in lungs may be utilized as a target for therapeutic interventions. According to this hypothesis, to achieve breathlessness relief, opioids should be administered in close proximity to their receptors in the PNECs and sensory C-fibers of the bronchial epithelium.

While recent studies suggested a potential causal link between type 1 diabetes mellitus (T1DM) but not type 2 diabetes mellitus (T2DM) and idiopathic pulmonary fibrosis (IPF), the involved mechanism remains unclear. Here, using a Mendelian randomization (MR) approach, we verified the causal relationship between the two types of diabetes mellitus and IPF and investigated the possible role of inflammation in the association between diabetes mellitus and IPF. Based on genome-wide association study (GWAS) summary data of T1DM, T2DM, and IPF, the univariable MR, multivariable MR (MVMR), and mediation MR were successively used to analyze the causal relationship. Inverse variance weighted was used as the main method to infer the causal effect, together with a series of sensitivity analyses. The univariable MR showed that only T1DM increased the risk of IPF, and there was no significant causal relationship between T2DM and IPF. The MVMR further verified that there was an independent direct causal effect of T1DM on IPF. Further mediation analysis showed that this effect was partly mediated by increasing C-X-C motif chemokine ligand 10 (CXCL10) and interleukin-12 subunit beta (IL-12B). In conclusion, T1DM is related to an increased risk of IPF. Notably, the causal effect was partially mediated by CXCL10 and IL-12B. Hence, monitoring T1DM patients may help in the early detection and prevention of IPF., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2025 the Author(s). Published by Wolters Kluwer Health, Inc.)

Abstract: Chronic widespread pain (CWP) is prevalent and associated with reduced life expectancy. Cardiovascular disease is one possible mechanism for this. The purpose of this study was to examine the association of CWP with arterial stiffness and carotid plaque measured using ultrasound to determine if shared environmental or genetic factors might account for any observed association. Around 3000 participants from the TwinsUK with CWP information and measures of carotid-femoral pulse wave velocity (cfPWV), carotid intima-media thickness (cIMT), and plaque were considered. The relationship between CWP and cfPWV, cIMT, and plaque was determined. UK Biobank data were used to replicate the association. Cholesky decomposition and multivariate pathway twin models were examined. Using a 2-sample Mendelian randomisation approach, the causal association between CWP and coronary artery disease was assessed. TwinsUK participants demonstrated a significant association between CWP and increased cfPWV consistent with arterial stiffening (OR = 1.35, P-value = 0.012), as well as the presence of carotid plaque (OR = 1.45, P-value = 0.8e-5). The twin modelling showed a common latent component and pathway underlying CWP, cfPWV, and carotid plaque, with genetic factors accounting for 68% and 90% of the latent factor variation, respectively. The 2-sample MR revealed a potential causal association between CWP and coronary artery disease. This study found that those with CWP have increased the risk of arterial stiffness and atherosclerosis and suggests that CWP leads to an increased risk of cardiovascular disease through genetic factors., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Purpose of Review: To describe recent findings of diisocyanate-mediated mechanisms in allergy and toxicology by addressing the role of microRNA (miR) in immune responses that may contribute to the development of occupational asthma (OA)., Recent Findings: Studies of diisocyanate asthma have traditionally focused on the immune and inflammatory patterns associated with diisocyanate exposures; however, recognized knowledge gaps exist regarding the detailed molecular mechanism(s) of pathogenesis. Recent studies demonstrate the critical role endogenous microRNAs play as gene regulators in maintaining homeostasis of the human body, and in the pathophysiology of many diseases including asthma. Given that diisocyanate-OA shares many pathophysiological characteristics with asthma, it is likely that miR-mediated mechanisms are involved in the pathophysiology of diisocyanate-OA. Recent reports have shown that changes in expression of endogenous miRs are associated with exposure to the occupationally relevant diisocyanates, toluene diisocyanate (TDI) and methylene diphenyl diisocyanate (MDI). Continued mechanistic study of these relevant miRs may lead to the development of novel biomarkers of occupational exposure and/or provide efficacious targets for therapeutic strategies in diisocyanate asthma., Summary: The molecular mechanisms underlying diisocyanate-OA pathophysiology are heterogeneous and complicated. In this review, we highlight recent research into the roles and potential regulation of miRs in diisocyanate-OA., (Copyright © Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

To investigate the association between the visceral adiposity index (VAI) and asthma using data from National Health and Nutrition Examination Survey 2003 to 2018 by a cross-sectional study. We explored the potential relationship between the VAI and asthma incidence via a cross-sectional study of the National Health and Nutrition Examination Survey from 2003 to 2018. Multiple logistic regression analysis, restricted cubic spline analysis and subgroup analysis were performed. Among the 80,312 participants, 1984 had been told by a doctor or other health professional, and 1142 still had asthma. With all confounders controlled, the VAI was positively associated with asthma incidence (odds ratios 1.04, 95% confidence interval: 1.01, 1.08). When comparing the second, third, and fourth VAI quartiles to the lowest quartile, the adjusted odds ratios (95% confidence intervals) for asthma risk were 1.02 (0.86, 1.21), 1.14 (0.96, 1.36), and 1.18 (1, 1.39), respectively (P for trend = .02). Subgroup analysis revealed no significant interaction effect among the subgroups (P > .05). The positive association was stronger in current asthma patients (odds ratios 1.13, 95% confidence interval: 1.03, 1.24). When comparing the second, third, and fourth VAI quartiles to the lowest quartile, the adjusted odds ratios for current asthma risk were 1.15 (0.81, 1.64), 1.29 (0.91, 1.84), and 1.51 (1.01, 2.24), respectively (P for trend .04). The restricted cubic spline regression analysis did not reveal a nonlinear correlation between the VAI and asthma or current asthma. Subgroup analysis revealed a significant interaction effect between age (P for interaction = .03) and diabetes status (P for interaction = .02). Except in the age ≥60 years, Less than high school, normal body mass index subgroup, VAI, and current asthma were positively correlated. A positive relationship between the VAI and asthma incidence was observed. In particular, there was a strong positive correlation between the VAI score and current asthma. According to the subgroup analysis, more attention should be given to individuals aged 40 to 59 years who have diabetes., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Taxus chinensis (TC) has tremendous therapeutic potential in alleviating non-small cell lung cancer (NSCLC), but the mechanism of action of TC remains unclear. Integrated bioinformatics and network pharmacology were employed in this study to explore the potential targets and molecular mechanism of TC against NSCLC. Data obtained from public databases were combined with appropriate bioinformatics tools to identify the common targets for TC and NSCLC. Common targets were uploaded to the Metascape database for gene ontology terms and Kyoto Encyclopedia of Genes and Genomes pathway analyses. A protein-protein interaction network was established, and topological analysis was performed to obtain hub genes. The expression of the hub genes in NSCLC tissues and their consequent effects on the prognosis of patients with NSCLC were confirmed using the Human Protein Atlas database and appropriate bioinformatics tools. Molecular docking was used to verify the binding affinity between the active ingredients and hub targets. We found 401 common targets that were significantly enriched in the cancer, MAPK signaling, and PI3K/Akt signaling pathways. Proto-oncogene tyrosine-protein kinase Src (SRC), mitogen-activated protein kinase 1, phosphoinositide-3-kinase, regulatory subunit 1 (PIK3R1), AKT serine/threonine kinase 1 (AKT1), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), and lymphocyte-specific protein tyrosine kinase were identified as the hub genes. Immunohistochemical results confirmed that the expression of SRC, mitogen-activated protein kinase 1, PIK3R1, AKT1, and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha was upregulated in the NSCLC tissues, while survival analysis revealed the expression of SRC, AKT1, PIK3R1, and lymphocyte-specific protein tyrosine kinase was closely related to the prognosis of patients with NSCLC. Molecular docking results confirmed all bioactive ingredients present in TC strongly bound to hub targets. We concluded that TC exhibits an anti-NSCLC role through multi-target combination and multi-pathway cooperation., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Abstract: Patients with coronavirus disease (COVID-19) commonly experience distressing and challenging respiratory symptoms. Interventions such as oxygen therapy, oral opiates, and traditional nebulizers like ipratropium bromide and salbutamol are variable in their efficacy, and therapy responses in patients are difficult to predict. The purpose of this study is to investigate the efficacy of nebulized fentanyl citrate on dyspnea, cough, and throat pain in patients with COVID-19 and evaluate the safety with any potential adverse events.In COVID-19, about 59% of patients will exhibit cough, 35% generalized body ache and sore throat, and 31% dyspnea. Some methods such as nebulized lidocaine, magnesium sulfate, and systemic opioids have been used to manage the respiratory symptoms. It has been previously shown that fentanyl nebulizer has beneficial effect in improving shortness of breath in patients with chronic obstructive pulmonary disease. The proposed theory behind that was that fentanyl decreased the rate of spontaneous respiratory rate, diminished the brain stem chemoreceptor response to hypoxia and hypercarbia, in addition to exhibiting a modulating effect on the brain stem. Therefore, we hypothesize that nebulized fentanyl has superior effect in improving shortness of breath and relieving cough compared to normal saline, in addition to its advantageous throat pain relief, while exhibiting fewer side effects in patients with COVID 19 infection. Therefore, this phase-III, randomized, comparative, parallel assignment, single-blinded clinical trial aims at assessing the efficacy and safety of nebulized fentanyl to suppress cough, improve breathlessness, and relieve throat pain in patients with COVID-19., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes mellitus. The main clinical manifestations of DPN include pain, numbness, paraesthesia, and weakness of the lower limbs which often leads to diabetic foot ulceration, eventually resulting in amputation. Based on Traditional Chinese Medicine theory, moxibustion has a great effect on treating and preventing DPN. However, randomized clinical trials done to evaluate the efficacy of this treatment are still lacking. Hence, this study is carried out to evaluate the effectiveness and safety of moxibustion therapy on diabetic peripheral neuropathy., Methods: This study will be a pilot, interventional, randomized, 2-armed, parallel, singled-masked, controlled trial. A total of 40 diabetes mellitus patients with peripheral neuropathy will be recruited and assigned randomly into 2 groups (moxibustion group and waiting group) at a 1:1 ratio. This trial consists of an 8-week intervention period and a 4-week follow-up period. During the intervention period, the moxibustion group will take 3 moxibustion sessions per week, whereas no intervention will be done on the waiting group to act as the control group. The outcome will be assessed by an outcome assessor who is unaware of the group assignment. The primary outcome will be pain assessment measured with algometry, Leeds Assessment of Neuropathic Symptoms and Signs pain scale, visual analogue scale, and neuropathy pain scale. The secondary outcome will be an evaluation of functional performance capacity with 6 minutes walking test, evaluation of the Foot and Ankle Ability Measure, and serum HbA1c and albumin levels., Discussion: We hope that this trial will provide valuable insights on the efficacy of moxibustion in the management of diabetic peripheral neuropathy., Trial Registration: ClinicalTrials.gov Registry No.: NCT04894461 (URL: https://clinicaltrials.gov/ct2/show/NCT04894461?term=NCT04894461&draw=2&rank=1) Registered on May 20, 2021., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Diagnosis of numerous cancers has been closely linked to the expression of certain long non-coding RNAs. This study aimed to evaluate levels of plasma FEZ family zinc finger 1 antisense RNA 1 (FEZF1-AS1) relative to non-small-cell lung carcinoma (NSCLC) diagnosis.The level of FEZF1-AS1 in the blood plasma of 126 NSCLC patients and 62 healthy controls was examined by quantitative real-time polymerase chain reaction.Plasma FEZF1-AS1 of the NSCLC group was increased compared with that in the control group (P < .0001). Plasma FEZF1-AS1 could distinguish patients with NSCLC from healthy individuals via the area under the ROC curve (AUC) of 0.855 (95% CI = 0.800-0.909; P = .000). FEZF1-AS1 combined with neuron-specific enolase increased the area under the (ROC) curve to 0.932 (95% CI = 0.897-0.968; P = .018). A high expression level of plasma FEZF1-AS1 was associated with some clinical features of NSCLC. Increased expression of FEZF1-AS1 greatly improved the risk of NSCLC (adjusted OR = 2.42; 95% CI = 1.23-4.76). A significant concentration-dependent relationship was noted between risk of NSCLC and higher FEZF1-AS1 expression (P for trend <.001).Plasma FEZF1-AS1 could potentially be used as a biomarker for NSCLC diagnosis.