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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.

Chronic obstructive pulmonary disease (COPD) is often associated with the co-occurrence of extra-pulmonary diseases, yet the underlying pathophysiology of comorbidities is poorly understood. In COPD patients, the bronchial epithelium often displays cellular damage and is chronically inflamed. The current study aimed to identify differentially expressed genes in bronchial epithelium of COPD patients with and without comorbidities. To this end, a genome-wide differential gene expression analysis was performed on bronchial epithelial samples of 123 severe COPD patients with and without the following comorbidities: anxiety, atherosclerosis, depression, hypercholesterolemia, hypertension, muscle wasting, osteoporosis, and low BMI. COPD patients with osteoporosis displayed higher expression of COL6A3 and lower expression of PHEX. Furthermore, COPD patients with hypercholesterolemia displayed a distinct bronchial epithelial gene expression profile, with 162 differentially expressed genes. No differentially expressed genes were identified for the other comorbidities. This study identified differentially expressed bronchial epithelial genes associated with osteoporosis and hypercholesterolemia in COPD patients.

Purpose: Combined lung-liver transplant (CLLT) is a complex yet life-saving procedure for patients with simultaneous end-stage lung and liver disease. Given the geographical allocation change to the lung allocation score (LAS) in 2017 and the recent SARS-CoV-2 outbreak in 2019, we aim to provide an updated analysis of the patient selection and outcomes of CLLTs.

Methods: The UNOS registry was used to identify all patients who underwent CLLT between January 2014 and June 2023. To account for the changes made to LAS in 2017, baseline characteristics and outcomes were compared between era 1 (before 2017) and era 2 (after 2017). Risk factors for mortality were analyzed using the Cox regression hazard models. Recipient survival of up to 3 years was analyzed using the Kaplan-Meier method.

Results: 117 CLLTs were performed (77.8% in era 2). Donor organs experienced significantly longer ischemic times (p = 0.039) and traveled longer distances (p = 0.025) in era 2. However, recipient (p = 0.79) and graft (p = 0.41) survival remained comparable at up to 3 years post-transplant between eras. CLLTs demonstrated similar long-term survival to isolated lung transplants (p = 0.73). Higher recipient LAS was associated with an increased mortality risk (HR 1.14, p = 0.034). Recipient diagnosis of idiopathic pulmonary fibrosis carried a 5.03-fold risk of mortality (p = 0.048) compared to those with cystic fibrosis.

Conclusion: In the post-2017 LAS change era, CLLTs are increasingly performed with comparable outcomes to isolated lung transplants. A careful, multidisciplinary approach to patient selection and management remains paramount to optimizing outcomes for this rare patient population.

Purpose: Staphylococcus aureus (SA) secretes pro-allergic molecules, including staphylococcal enterotoxins (SEs) and serine protease-like proteins (Spls). While IgE sensitization to SE has been relatively well documented in relation to severe eosinophilic late-onset asthma, the clinical implications of IgE sensitization to Spls remain unclear. We explored the clinical relevance of Spl-IgE in late-onset asthmatics.

Methods: Adults with late-onset asthma (onset age ≥ 40 years) were prospectively enrolled. Demographic and clinical characteristics were assessed, and serum levels of total IgE, SE-IgE, and SplA-IgE were measured. Nasal swabs were obtained to assess SA colonization.

Results: Among 109 participants, SplA-IgE levels were significantly associated with blood eosinophilia, total IgE, SE-IgE sensitization, and male sex, but not with SA colonization, asthma severity, or lung function.

Conclusion: Sensitization to SplA-IgE may indicate a type 2 inflammatory phenotype, but its role in asthma warrants further investigation.

Purpose: Cystic fibrosis (CF) is a genetic disease caused by mutations in the CFTR gene, leading to multisystemic complications, particularly in the lungs. CFTR dysfunction results in altered ion transport, chronic inflammation, and progressive lung damage. The triple therapy elexacaftor/tezacaftor/ivacaftor (ETI) has demonstrated significant improvements in pulmonary function and quality of life. This study aimed to evaluate the anti-inflammatory effects of ETI by analysing systemic cytokine profiles over 12 months.

Methods: A prospective study included 32 CF patients ≥ 18 years with at least one delF508 mutation, undergoing ETI therapy. Clinical stability was ensured prior to therapy initiation. Demographic data, BMI (Body Mass Index), FEV1% (Forced expiratory Volume in the first second), VR/TLC (residual volume/total lung capacity) and sweat chloride concentrations were recorded at baseline, 6 months and 12 months. Inflammatory markers, including fibrinogen, C-reactive protein (CRP), and a panel of 8 cytokines, were measured using multiplex bead-based immunoassays and electrochemiluminescence. Longitudinal changes were analysed using mixed-effects models and statistical tests, with significance set at p < 0.05.

Results: During a 12-month follow-up, the neutrophils number and proinflammatory biomarkers analyzed, fibrinogen, CRP, GM-CSF, IFN- γ, IL-1 α, IL-1 β, IL-8 (CXCL8), IL-12p70, IL-17A (CTLA-8), and TNF-α, significantly decreased, while eosinophils remained stable. Mixed-effects models confirmed the significant association of inflammatory biomarkers with FEV1, BMI, sweat chloride levels, and VR/TLC highlighting the role of inflammation in the progression of CF.

Conclusions: ETI demonstrated marked anti-inflammatory effects in CF patients, reducing systemic inflammation and improving clinical parameters.

Purpose: Cholesterol regulation is essential to maintain pulmonary homeostasis. Studies suggest that increased high-density lipoprotein cholesterol (HDL-C) levels correlate with better lung function. However, the longitudinal association of HDL-C with lung function remains unknown. We aimed to analyze the long-term correlation of HDL-C with lung function decline in a population-based cohort study.

Methods: We included 7,652 participants from a prospective community-based cohort study in South Korea. Participants were categorized into five trajectory groups based on repeated HDL-C measurements. Generalized linear mixed models with random intercepts and slopes were used to examine the longitudinal relationship between HDL-C levels and lung function decline within these groups.

Results: In the five HDL-C trajectory group analyses, the very low HDL-C trajectory group (Group 1) showed faster declines in forced vital capacity (FVC) (-3.1 mL/year) and forced expiratory volume in one second (FEV₁) (-3.1 mL/year) than the middle HDL-C group (Group 3, the reference group) did. The low HDL-C trajectory group (Group 2) also exhibited faster FVC (-1.5 mL/year) and FEV₁ (-1.7 mL/year) declines than the middle HDL-C group; however, the estimated difference was smaller than that in Group 1. Faster lung function decline in the low HDL-C trajectory group was consistently observed even when the population was analyzed using three- or four-HDL-C trajectory groups instead of five.

Conclusion: Participants in the low HDL-C trajectory groups experienced a more rapid lung function decline over time than the reference groups, suggesting a negative longitudinal association between HDL-C and lung function decline.