Lung最新文献

Pyruvate kinase M2 (PKM2) is a critical enzyme regulating cell metabolism and growth under different physiological conditions. In its metabolic role, PKM2 catalyzes the final and also a rate-limiting reaction in the glycolytic pathway, converting phosphoenolpyruvate (PEP) to pyruvate while phosphorylating adenosine diphosphate (ADP) to pyruvate and adenosine-triphosphate (ATP). Also, PKM2 has been reported to function as a protein kinase that regulates gene transcription and expression involved in cellular growth and survival. Current studies have focused on the glycolytic and non‑glycolytic functions of PKM2 in various tissues and organs. In this review, we summarize the in-depth role of PKM2 in the pathogenesis in pulmonary diseases including chronic obstructive pulmonary disease (COPD), asthma, pulmonary arterial hypertension (PAH), acute lung injury (ALI), pulmonary fibrosis, infectious lung disease and lung cancer. We also discuss its potential applications in disease diagnosis and therapies.

Poor or worsening functional status of lung transplant (LTx) candidates is a key risk factor for waitlist and post-transplant mortality. As more critically ill adults and children are listed for LTx, the use of extracorporeal membrane oxygenation (ECMO) as bridge to LTx is also increasing. Sustaining optimal functional status while on the waitlist to LTx is crucial for LTx candidates as deterioration in functional status can negatively impact pre- and post-LTx outcomes. We conducted an analysis of the United Network for Organ Sharing Registry which showed that most patients (70%) on ECMO successfully bridged to LTx. The majority had severely limited functional status at the time of waitlisting but 96% of adults requiring ECMO on the waitlist for LTx either maintained or improved functional status from the time of waitlist to the time of LTx while all children on ECMO maintained or improved their functional status. With continuing medical and technical advances, the use of ECMO may also evolve to improve LTx candidates' functional status.

Purpose: Pregnancy is a risk factor for the development of obstructive sleep apnea (OSA) and for worsening of asthma; the interaction between the two disorders is not well described. We aimed to examine airway mechanics in pregnant patients with and without OSA and asthma.

Methods: We studied 217 women with BMI above 25 early in the second trimester of pregnancy. Airways resistance was measured using the forced oscillation technique at 5 Hz (R5), 20 Hz (R20), and 35 Hz (R35). All values were expressed as % predicted. level III sleep studies were scored according to the recommended AASM rules; OSA was diagnosed by AHI ≥ 5 events per hour. Asthma was defined by medical history and record review.

Results: Of the 217 women tested, 53 had OSA and 66 had asthma. R20 and R35 were increased in women with both OSA and asthma compared to those with neither asthma nor OSA (adjusted mean difference (aMD) for R20 was 19.7, CI 3.4-36.0, p value = 0.02; aMD for R35 was 36.9 CI 12.4-61.5, p value = 0.003). There was a significant increase in R35 for women with OSA as opposed to those without (aMD 17.6 (CI 1.4-33.8; p value = 0.03).

Conclusion: Pregnant women with both OSA and asthma have higher central airways resistance and upper airway resistance as measured at R20 and R35, respectively, compared to those with neither OSA nor asthma. Further work is needed to understand mechanisms underlying the synergistic effects of OSA and asthma on airways mechanics.

Pericytes, specialized mural cells residing within the basement membrane of pulmonary microvessels, participate in various biological processes, including vascular homeostasis, immunomodulation, and tissue repair. However, these beneficial physiological roles can be detrimental under pathological conditions. Numerous pulmonary fibrosis models have demonstrated pericyte differentiation into scar-forming myofibroblasts, leading to collagen deposition and matrix remodeling, thereby contributing to tissue fibrosis. Similarly, pericytes play crucial roles in inflammatory diseases. This review aims to explore the dual roles of pericytes in the lung and the underlying mechanisms of their role conversion, providing insights for developing therapeutic strategies targeting these cells.

Oxidative stress has been implicated in lung injury and repair. We seek to understand how alterations in the plasma redox potential (Eh) of the thiol disulfide couple cysteine (Cys) and cystine (CySS) (Eh Cys/CySS) affect this process. Previously, we reported that Eh Cys/CySS oxidation promotes a pro-fibrotic phenotype in lung fibroblasts and identified the cystine/glutamate exchanger solute carrier family 7, member 11 (Slc7a11) as a regulator of Eh Cys/CySS. We also observed that pharmacological agents capable of altering Slc7a11 expression affect lung fibroblast phenotype in vitro. We hypothesized that alterations in Slc7a11 expression would affect lung injury in vivo and set out to test this in C57Bl6 mice exposed to bleomycin. However, we did not observe changes in bleomycin-induced lung injury in animals treated with pharmacological alterations in Slc7a11 expression or when Slc7a11 knockout animals were tested. Thus, the role of Slc7a11 in lung injury remains uncertain.

Objectives: To systematically review the efficacy and safety, both short and long-term, of superior laryngeal nerve block (SLNB) for managing neuropathic cough.

Methods: A literature search was conducted using the keywords "Superior laryngeal nerve block," "Neurogenic Cough," "Neuropathic Cough," and "Refractory Chronic Cough." The primary outcome was cough-specific quality of life (QoL), evaluated with validated patient-reported outcome measures (PROMs) such as the Leicester Cough Questionnaire (LCQ), Cough Severity Index (CSI), and Hull Airway Reflux Questionnaire (HARQ). Additional data included SLNB technique, cough duration, use of neuromodulators and Behavioral Cough Suppression Therapy (BCST), injection frequency, vocal fold dysfunction (VFD), and adverse events. Quality assessments used the Methodological Index for Non-Randomized Studies (MINORS) criteria.

Results: Ten studies comprising 625 patients were included. The average cough duration prior to intervention was 78 months, with a mean follow-up of 5.01 months. Patients received an average of 2.5 injections. Short-term outcomes showed consistent improvements in PROMs and cough perception. Long-term outcomes (beyond three months) were reported in four studies, with minimal variations but no statistical comparisons to baseline scores. Significant heterogeneity was noted across studies, including differences in assessment protocols and adjunctive therapies. No significant adverse events were reported.

Conclusion: SLNB is a safe and effective treatment for refractory chronic cough, either alone or with systemic medications. However, the variability among studies highlights the need for standardized protocols and further research with long-term follow-up to confirm its efficacy.

Chronic cough is a significant burden on patient quality of life and is associated with poor health outcomes. Chronic cough may be a result of neural hypersensitivity due to changes in both the peripheral and the central nervous systems, although the exact mechanisms underlying its pathogenesis are not completely understood. Opioid receptors, specifically kappa and mu, are potential therapeutic targets in the management of chronic cough because they play a pivotal role in both the peripheral and the central neural pathways implicated in the act of coughing. Morphine, a mu opioid receptor agonist, is an effective cough modulator; however, mu receptor agonists are part of a drug class that can induce respiratory depression and euphoria, with strong reinforcing properties that may lead to excessive use and abuse. Drugs with a dual-acting mechanism of kappa receptor agonism and mu receptor antagonism may be effective in the management of chronic cough without the potential for abuse. This review summarizes the current understanding of the mechanisms of cough hypersensitivity, the role of the kappa and mu receptors in the neurophysiology of cough, and the clinical potential of targeting these receptors as a novel way of managing chronic cough.

Introduction: Studies indicate that chronic treatment with mucoactive drugs may reduce COPD exacerbation rates. This real-world, multicenter, prospective, observational study aimed to determine the effect of long-term mucoactive treatment on exacerbations in patients with COPD in the Czech Republic.

Methods: 452 adult patients on the Czech Multicenter Research Database of COPD with post-bronchodilator FEV₁ ≤ 60% of predicted value received standard of care and were followed up for 5 years. For the first 24 months, 81 patients received regular thiol-based mucoactive drugs (77 erdosteine, 4 N-acetylcysteine) at the discretion of the treating physician and 371 patients had no mucoactive treatment (control group). Erdosteine was fully reimbursed, and NAC was partially reimbursed for COPD patients. The annual number/rate of COPD exacerbations over 5 years was monitored.

Results: Patients receiving mucoactive treatment for 24 months had a significantly larger reduction from baseline in all exacerbations compared to the control group (- 0.61 vs - 0.18, p = 0.026; - 0.54 vs - 0.09, p = 0.007; - 0.55 vs 0.04, p = 0.005; - 0.67 vs 0.13, p = 0.002; - 0.53 vs 0.10, p = 0.019 in the first to fifth year, respectively). The reduction in moderate exacerbations was also significantly larger in those receiving mucoactive treatment versus no mucoactive treatment. The exacerbation rate was reduced to a greater extent in the subgroups with cough or with stage 3‒4 COPD who received mucoactive treatment but was independent of the use of inhaled corticosteroids (ICS).

Conclusion: Mucoactive treatment for two years reduced the number of COPD exacerbations (all, moderate) over five years of follow-up. The reduction in exacerbations was more pronounced in patients with cough or with stage 3‒4 COPD but was independent of the use of ICS.

Purpose: Potassium-competitive acid blockers (P-CABs) are a newer class of acid suppressants with convenient dosing and a rapid onset of action, while showing efficacy comparable to proton pump inhibitors (PPIs) in treating peptic symptoms of gastroesophageal reflux disease (GERD). This study aimed to assess the effect of P-CABs on GERD-related chronic cough.

Methods: This randomized, double-blind, active-controlled, exploratory trial evaluated adults with chronic cough (≥ 8 weeks) and a recent physician diagnosis of GERD or peptic symptoms (< 1 month). Participants were randomized (1:1) to receive either fexuprazan 40 mg or esomeprazole 40 mg (PPI) once daily for eight weeks, along with matched placebos. The primary endpoint was the change in Leicester Cough Questionnaire (LCQ) score from baseline. Secondary endpoints included changes in the cough severity Numerical Rating Scale (NRS) and Reflux Disease Questionnaire (RDQ) scores. Safety was evaluated through monitoring adverse events.

Results: Of the 190 subjects recruited, 161 met the selection criteria and were randomized, and 146 completed the trial. The participants were predominantly female (74.3%, mean age 39 ± 12 years). After 8 weeks of treatment, cough-related quality of life improved significantly, with comparable LCQ scores change between the groups (fexuprazan: 4.9 ± 4.0 vs. esomeprazole: 5.3 ± 3.8, p = 0.558). Changes in cough severity NRS and RDQ scores were also similar between the groups. Adverse events were comparable and consisted mostly of mild symptoms.

Conclusion: These findings support the potential of P-CABs as a promising alternative to PPIs for patients with chronic cough requiring acid-suppressive therapy.