Non-allergic eosinophilic inflammation and airway hyperresponsiveness induced by diesel engine exhaust through activating ILCs.

RATIONALE: Diesel engine exhaust (DEE) is associated with the development and exacerbation of asthma. Studies have shown that DEE can aggravate allergen-induced eosinophilic inflammation in lung. However, it remains not clear that whether DEE alone could initiate non-allergic eosinophilic inflammation and airway hyperresponsiveness (AHR) through innate lymphoid cells (ILCs) pathway. OBJECTIVE: This study aims to investigate the airway inflammation and hyperresponsiveness and its relationship with ILC after DEE exposure. METHOD: Non-sensitized BALB/c mice were exposed in the chamber of diesel exhaust or filtered air for 2, 4, and 6 weeks (4 h/day, 6 days/week). Anti-CD4 mAb or anti-Thy1.2 mAb was administered by intraperitoneal injection to inhibit CD4+T or ILCs respectively. AHR、airway inflammation and ILCs were assessed. RESULT: DEE exposure induced significantly elevated level of neutrophils, eosinophils, collagen content at 4, 6 weeks. Importantly, the airway AHR was only significant in the 4weeks-DEE exposure group. No difference of the functional proportions of Th2 cells was found between exposure group and control group. The proportions of IL-5+ILC2, IL-17+ILC significantly increased in 2, 4weeks-DEE exposure group. After depletion of CD4+T cells, both the proportion of IL-5+ILC2 and IL-17A ILCs was higher in the 4weeks-DEE exposure group which induced AHR, neutrophilic and eosinophilic inflammation accompanied by the IL-5, IL-17A levels. CONCLUSION: Diesel engine exhaust alone can imitate asthmatic characteristics in mice model. Lung-resident ILCs are one of the major effectors cells responsible for a mixed Th2/Th17 response and AHR.

Targeting TtVgR via siRNA Knockdown Elicits Ovarian Cell Death in the Tri-spine Horseshoe Crab.

The vitellogenin present in the bloodstream undergoes internalization into developing oocytes through the vitellogenin receptor (VgR), a process mediated by receptor-mediated endocytosis. VgR plays a crucial role in facilitating the accumulation of vitellogenin and the maturation of oocytes. In this study, we characterized a Tachypleus tridentatus vitellogenin receptor (TtVgR) gene from the tri-spine horseshoe crab, revealing a length of 1956 bp and encoding 652 amino acid residues with 12 exons. TtVgR has a molecular weight of 64.26 kDa and an isoelectric point of 5.95. Predictions indicate 85 phosphorylation sites and 7 glycosylation sites within TtVgR. Transcriptional analysis demonstrated specific expression of TtVgR in the ovary and yellow connective tissue. TtVgR was identified and distributed in the plasma membrane of oocytes. The siRNA-mediated TtVgR knockdown significantly reduced the transcriptional activity of TtVgR. This depletion induced excessive ROS production, resulting in DNA damage in ovarian primary cells. TUNEL and flow cytometry analyses confirmed ovarian cell apoptosis following TtVgR knockdown, indicating DNA damage in ovarian primary cells. These findings underscore the importance of TtVgR in ovarian cell development, suggesting its potential involvement in vitellogenesis and oocyte maturation. This knowledge may inform innovative breeding strategies and contribute to the sustainable management and conservation of the tri-spine horseshoe crab.

Potassium-Competitive Acid Blocker Versus Proton Pump Inhibitor: A Pilot Study on Comparable Efficacy in the Treatment of Gastroesophageal Reflux-Related Cough.

Acid inhibitors have been considered in treating gastroesophageal reflux-related cough (GERC). Compared to proton pump inhibitors (PPIs), potassium-competitive acid blockers (P-CABs) have more potent and durable effects on anti-acid secretion. However, whether vonoprazan and esomeprazole have different therapeutic effects on GERC remains unknown. Patients diagnosed with GERC were enrolled in our study and randomly treated with vonoprazan (20 mg, once daily, P-CAB) or esomeprazole (20 mg, twice daily, PPI) for two months. A prokinetic agent was also administered. Patients were followed up once a month. Cough severity visual analogue scale (VAS) was measured as the primary outcome, while cough symptom score (CSS) and scores for cough-related quality-of-life or reflux-related symptoms were the secondary endpoints. A total of 50 patients completed the study, with 25 patients in each group. P-CAB and PPI groups showed similar decreases in cough severity VAS and CSS scores after the 2-month treatment (all P < 0.001). For quality-of-life, the Leicester Cough Questionnaire (LCQ) score increased significantly from baseline in both groups, but the P-CAB group had greater improvement and a higher LCQ score in month 2 (all P ≤ 0.05). For reflux-related symptoms, the Hull Airway Reflux Questionnaire (HARQ) score declined substantially over time in the P-CAB group, while the reflux symptom index (RSI) score decreased in both groups. The P-CAB group tended to have a lower HARQ (P = 0.051) and RSI (P = 0.069) scores in month 2. In conclusion, vonoprazan may be comparable to esomeprazole in cough symptom relief in GERC during the 2-month treatment period, but possibly provides better gains on classic reflux symptoms and quality-of-life. The long-term efficacy of P-CABs on GERC may be worth further exploration. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2200067089.

A Wash-Free Spheres-on-Sphere Strategy for On-Site and Multiplexed Biosensing.

Respiratory infections and food contaminants pose severe challenges to global health and the economy. A rapid on-site platform for the simultaneous detection of multiple pathogens is crucial for accurate diagnosis, appropriate treatment, and a reduced healthcare burden. Herein, we present a spheres-on-sphere (SOS) platform for multiplexed detection using a portable Coulter counter, which employs millimeter- and micron-sized spheres coupled with antibodies as multitarget probes. The assay allows for quantitative detection of multiple analytes within 20 min by simple mixing, enabling on-site detection. The platform shows high accuracy in identifying three respiratory viruses (SARS-CoV-2, influenza A virus, and parainfluenza virus) from throat swab samples, with LOD of 50.7, 32.4, and 49.1 pg/mL. It also demonstrates excellent performance in quantifying three mycotoxins (aflatoxin B1, deoxynivalenol, and ochratoxin A) from food samples. The SOS platform offers a rapid on-site approach with high sensitivity and specificity for applications in resource-limited settings.

Profile of cough triggers and their relationship with capsaicin cough sensitivity in chronic cough.

BACKGROUND: Cough hypersensitivity is an important part of the neurophysiology of cough, which presents with increased cough response to a lower level of stimuli or triggers. Classification of stimuli might bring about additional insight into the underlying mechanisms and management. OBJECTIVES: This study investigated the profile of cough triggers in chronic cough patients and their relationship with capsaicin cough sensitivity. DESIGN: This was a cross-sectional observational study. METHODS: We enrolled patients with different causes of chronic cough from 2006 to 2021. Cough triggers were defined as cough response to chemical triggers, mechanical triggers, meal triggers, or thermal trigger. Cough sensitivity to capsaicin was evaluated by the capsaicin challenge test, which was expressed as the lowest concentration of capsaicin inducing 5 or more coughing (C5). RESULTS: Among 1211 patients with chronic cough, 1107 (91.4%) patients reported at least one cough trigger. Chemical triggers (66.9%) were the most common cough triggers, followed by thermal exposure (50.6%), mechanical triggers (48.2%), and meal triggers (21.2%). There was no difference in the proportion of chemical triggers among different etiologies. Patients with refractory chronic cough reported the highest prevalence of cough triggers (97.1%). A higher number of meal triggers (34.9%) was associated with gastroesophageal reflux-related cough, and meal triggers and mechanical triggers were more common in refractory chronic cough. Among 254 patients who completed capsaicin challenge test, both the number of total triggers and the number of chemical triggers had a significant but mild correlation with capsaicin cough sensitivity. CONCLUSION: Cough hypersensitivity as reflected by a variety of cough triggers is a common feature in chronic cough patients, but different etiologies present specific profiles of cough triggers, which could not be evaluated comprehensively by capsaicin cough sensitivity.

Gabapentin alleviated the cough hypersensitivity and neurogenic inflammation in a guinea pig model with repeated intra-esophageal acid perfusion.

OBJECTIVE: The anti-tussive effect of gabapentin and its underlying neuromodulatory mechanism were investigated via a modified guinea pig model of gastroesophageal reflux-related cough (GERC). METHODS: Intra-esophageal perfusion with hydrochloric acid (HCl) was performed every other day 12 times to establish the GERC model. High-dose gabapentin (48 mg/kg), low-dose gabapentin (8 mg/kg), or saline was orally administered for 2 weeks after modeling. Cough sensitivity, airway inflammation, lung and esophagus histology, levels of substance P (SP), and neurokinin-1 (NK1)-receptors were monitored. RESULTS: Repeated intra-esophageal acid perfusion aggravated the cough sensitivity in guinea pigs in a time-dependent manner. The number of cough events was significantly increased after 12 times HCl perfusion, and the hypersensitivity period was maintained for 2 weeks. The SP levels in BALF, trachea, lung, distal esophagus, and vagal ganglia were increased in guinea pigs receiving HCl perfusion. The intensity of cough hypersensitivity in the GERC model was significantly correlated with increased SP expression in the airways. Both high and low doses of gabapentin administration could reduce cough hypersensitivity exposed to HCl perfusion, attenuate airway inflammatory damage, and inhibit neurogenic inflammation by reducing SP expression from the airway and vagal ganglia. CONCLUSIONS: Gabapentin can desensitize the cough sensitivity in the GERC model of guinea pig. The anti-tussive effect is associated with the alleviated peripheral neurogenic inflammation as reflected in the decreased level of SP.

Artificial Intelligence-Based Imaging Transcoding System for Multiplex Screening of Viable Foodborne Pathogens.

Multiplex detection of viable foodborne pathogens is critical for food safety and public health, yet current assays suffer trade-offs between cost, assay complexity, sensitivities, and the specificity between live and dead bacteria. We herein developed a sensing method using artificial intelligence transcoding (SMART) for rapid, sensitive, and multiplex profiling of foodborne pathogens. The assay utilizes the programmable polystyrene (PS) microspheres to encode different pathogens, inducing subsequent visible signals under conventional microscopy that can be analyzed using a customized, artificial intelligence-computer vision, which was trained to decode the intrinsic properties of PS microspheres to reveal the numbers and types of pathogens. Our approach enabled the rapid and simultaneous detection of multiple bacteria from egg samples of <102 CFU/mL without DNA amplification and showed strong consistency with the standard microbiologic and genotypic methods. We adopted our assay through phage-guided targeting to enable the discrimination between live and dead bacteria.

Clinical characteristics of protracted bacterial bronchitis in adults.

There are few data regarding adult protracted bacterial bronchitis (PBB). This study aimed to delineate the clinical features of PBB and evaluate their potential diagnostic value in adults. We recruited 55 adult patients with PBB and selected randomly 220 patients with non-PBB as control. A diagnosis of PBB was considered if patients had a cough lasting ≥3 weeks, no abnormalities of chest computed tomography, positive bacterial culture in sputum and/or response well to oral moxifloxacin for 1-4 weeks. The clinical manifestations and laboratory investigations were compared between PBB patients and non-PBB patients. Of the 55 patients with PBB, approximately three-fifths (34, 61.8%) were females with a median age of 46.0 years, which were similar to that of patients with non-PBB. We observed a shorter cough duration in PBB than non-PBB (median 3.0 versus 24.0 months, p < 0.001). Compared to non-PBB patients, PBB patients had higher incidences of productive cough, yellow phlegm and a sensation of mucus in the throat (SMIT) (all p < 0.001). Sputum neutrophils and lymphocytes were markedly elevated in PBB patients than non-PBB patients (both p = 0.004). Bacterial pathogens were detected in eight (28.6%) of 28 cases with PBB. The multivariate analyses showed yellow phlegm, productive cough, SMIT, increased sputum lymphocytes (≥2.3%) and cough duration ≤8.5 months with moderate sensitivity (50.9-81.8%) and moderate-high specificity (60.5-94.4%) for determining PBB. In summary, adults with PBB are characterized by productive cough, yellow phlegm, SMIT and neutrophilic airway inflammation. These cough features and increased sputum lymphocytes may be useful to indicate PBB.

Cartridge voltage-sensitive micropump immunosensor based on a self-assembled polydopamine coating mediated signal amplification strategy.

Current biosensing detection assays were developed to focus on rapid, low-cost, stable detection for clinical diagnosis and food safety monitoring. In this work, a novel portable cartridge voltage-sensitive micropump immunosensor (CVMS) biosensing device based on the integration of the microchannel circuit biosensing principle and polydopamine (PDA) was presented for rapid and sensitive detection of pathogenic factors in real samples at trace levels. The CVMS can sensitively evaluate voltage signal changes caused by clogging effects in the closed-loop circuit when the insulated microspheres pass through the microchannel. The targets could trigger the immune reaction between antibody-antigens that leads to the change in the concentration of horseradish peroxidase (HRP). And the HRP was further employed to catalyze the polymerization of dopamine into PDA, resulting in the rapid formation of the magnetic @PDA nanoparticles (MNP@PDA) with core-shell structures. The abundant functional groups on the MNP@PDA surface can efficiently adsorb polystyrene microspheres, thus causing changes in the number of polystyrene microspheres (PS). The CVMS can accurately monitor the change of PS with a portable device, which weighs less than 0.8 kg and costs only $50. The completion of CVMS takes 90 min to complete. The limit of detection of this immunosensor for procalcitonin and ochratoxin A were 42 pg/mL and 77 pg/mL, respectively, which improved about 15 folds and 38 folds, respectively, than those of enzyme-linked immunosorbent assay.

Comparison of pedicle screw fixation with or without cement augmentation for treating single-segment isthmic spondylolisthesis in the osteoporotic spine.

The present study examined the necessity of cement-augmented pedicle screw fixation in osteoporotic patients with single-segment isthmic spondylolisthesis.Fifty-nine cases were reviewed retrospectively. Thirty-three cases were in the polymethylmethacrylate-augmented pedicle screw (PMMA-PS) group, and the other 26 cases were in the conventional pedicle screw (CPS) group. Evaluation data included operation time, intraoperative blood loss, hospitalization cost, hospitalization days, rates of fusion, screw loosening, bone cement leakage, visual analogue scale (VAS) scores, Oswestry disability index (ODI), lumbar lordosis (LL), pelvic tilt (PT) and sacral slope (SS).The operation time and blood loss in the CPS group decreased significantly compared to those in the PMMA-PS group. The average hospitalization cost of the PMMA-PS group was significantly higher than that of the CPS group. There was no significant difference in the average hospital stay between the 2 groups. The initial and last follow-up postoperative VAS and ODI scores improved significantly in the two groups. There were no significant differences in VAS and ODI between the 2 groups at each time point. The last postoperative spine-pelvic parameters were significantly improved compared with those preoperatively. In the PMMA-PS group, the fusion rate was 100%. The fusion rate was 96.15% in the CPS group. No significant difference was found between the two groups for the fusion rate. Nine patients in the PMMA-PS group had bone cement leakage. There was no screw loosening in the PMMA-PS group. There were 2 cases of screw loosening in the CPS group. There were no significant differences in screw loosening, postoperative adjacent segment fractures, postoperative infection or postoperative revision between the 2 groups. The use of PMMA-PS on a regular basis is not recommended in posterior lumbar interbody fusion for the treatment of single-segment isthmic spondylolisthesis with osteoporosis.

Advances in epidemiology, etiology, and treatment of community-acquired pneumonia / 中华预防医学杂志

Community-acquired pneumonia (CAP) is the third leading cause of death worldwide and one of the most commonly infectious diseases. Its epidemiological characteristics vary with host and immune status, and corresponding pathogen spectrums migrate over time and space distribution. Meanwhile, with the outbreak of COVID-19, some unconventional treatment strategies are on the rise. This article reviewed the epidemiological characteristics, pathogen spectrum and treatment direction of CAP in China over the years, and aimed to provide guidance for the diagnosis and treatment of CAP in clinical practice.

Aspergillus tracheobronchitis with Birt-Hogg-Dubè syndrome as a rare cause of chronic cough.

BACKGROUND: Aspergillus tracheobronchitis (ATB) is confined as a condition of chronic superficial infection of tracheobronchial tree. Its diagnosis is difficult due to atypical manifestations and low detective rate of Aspergillus thus far. CASE PRESENTATION: Herein, we presented a 45-year-old male patient with a sole chronic productive cough for five years referred to our cough specialist clinic. Chest high-resolution computed tomography showed multiple lung cysts predominantly located in the subpleural lesions and near the mediastinum. Neither bacteria nor fungi were identified by sputum culture. However, metagenomic next-generation sequencing in sputum detected Aspergillus fumigatus DNA. The genetic testing of whole blood suggested the germline mutation of the tumor suppressor gene folliculin, supporting a diagnosis of Birt-Hogg-Dubé (BHD) syndrome. His productive cough symptom significantly improved after receiving itraconazole treatment for 2 months. After discontinuation of antifungal treatment, there was no relapse for four months follow-up. A diagnosis of ATB with BHD syndrome was eventually established in this patient. CONCLUSION: ATB should be considered in any patient with prolonged unexplained productive cough. Next-generation sequencing technologies may be useful to identify ATB which is uncommon and easily ignored in clinical practice.

Effects of treatment with montelukast alone, budesonide/formoterol alone and a combination of both in cough variant asthma.

BACKGROUND: Whether cysteinyl-leukotriene receptor antagonists (LTRAs) have a similar antitussive effect to inhaled corticosteroids and long-acting ß2-agonist (ICS/LABA), and that LTRA plus ICS/LABA is superior to LTRAs alone or ICS/LABA alone in treating cough variant asthma (CVA) remain unclear. This study aimed to investigate and compare the efficacy of montelukast alone, budesonide/formoterol alone and the combination of both in the treatment of CVA. METHODS: Ninety-nine CVA patients were assigned randomly in a 1:1:1 ratio to receive montelukast (M group: 10 mg, once daily), budesonide/formoterol (BF group: 160/4.5 µg, one puff, twice daily), or montelukast plus budesonide/formoterol (MBF group) for 8 weeks. The primary outcomes were changes in the cough visual analogue scale (VAS) score, daytime cough symptom score (CSS) and night-time CSS, and the secondary outcomes comprised changes in cough reflex sensitivity (CRS), the percentage of sputum eosinophils (sputum Eos%) and fractional exhaled nitric oxide (FeNO). CRS was presented with the lowest concentration of capsaicin that induced at least 5 coughs (C5). The repeated measure was used in data analysis. RESULTS: The median cough VAS score (median from 6.0 to 2.0 in the M group, 5.0 to 1.0 in the BF group and 6.0 to 1.0 in the MBF group, all p < 0.001), daytime CSS (all p < 0.01) and night-time CSS (all p < 0.001) decreased significantly in all three groups after treatment for 8 weeks. Meanwhile, the LogC5 and sputum Eos% improved significantly in all three groups after 8 weeks treatment (all p < 0.05). No significant differences were found in the changes of the VAS score, daytime and night-time CSSs, LogC5 and sputum Eos% among the three groups from baseline to week 8 (all p > 0.05). The BF and MBF groups also showed significant decreases in FeNO after 8 weeks treatment (p = 0.001 and p = 0.008, respectively), while no significant change was found in the M group (p = 0.457). Treatment with MBF for 8 weeks significantly improved the FEV1/FVC as well as the MMEF% pred and decreased the blood Eos% (all p < 0.05). CONCLUSIONS: Montelukast alone, budesonide/formoterol alone and a combination of both were effective in improving cough symptom, decreasing cough reflex sensitivity and alleviating eosinophilic airway inflammation in patients with CVA, and the antitussive effect and anti-eosinophilic airway inflammation were similar. Trial registration ClinicalTrials.gov, number NCT01404013.

Prevalence and risk factors for postinfectious cough in discharged patients with coronavirus disease 2019 (COVID-19).

Background: Cough is one of the most common symptoms of coronavirus disease 2019 (COVID-19). However, the prevalence of persistent cough in recovered patients with COVID-19 during a longer follow-up remained unknown. This study aims to investigate the prevalence, and risk factors for postinfectious cough in COVID-19 patients after discharge. Methods: We conducted a follow-up study for 129 discharged patients with laboratory-confirmed COVID-19 in two large hospitals located in Hubei Province, China from January 2020 to December 2020. Baseline demographics, comorbidities and smoking history were extracted from the medical record. Current symptoms and severity were recorded by a uniform questionnaire. Spirometry, diffuse function and chest computed tomography (CT) were performed on part of patients who were able to return to the outpatient department at follow-up. Results: The median (interquartile range) follow-up time was 8.1 (7.9-8.5) months after discharge. The mean (standard deviation) age was 51.5 (14.9) years and 57 (44.2%) were male. A total of 27 (20.9%) patients had postinfectious cough (>3 weeks), 6 patients (4.7%) had persistent cough by the end of follow-up, including 3 patients with previous chronic respiratory diseases or current smoking. Other symptoms included dyspnea (6, 4.7%), sputum (4, 3.1%), fatigue (4, 3.1%), and anorexia (4, 3.1%) by the end of follow-up. Thirty-six of 41 (87.8%) patients showed impaired lung function or diffuse function, and 39 of 50 (78.0%) patients showed abnormal CT imaging. Patients with postinfectious cough demonstrated more severe and more frequent cough during hospitalization (P<0.001), and more chronic respiratory diseases (P=0.01). In multivariate logistic regression analysis, digestive symptoms during hospitalization [odds ratio (OR) 2.95, 95% confidence interval (CI): 1.10-7.92] and current smoking (OR 6.95, 95% CI: 1.46-33.14) were significantly associated with postinfectious cough of COVID-19. Conclusions: A small part of patients developed postinfectious cough after recovery from COVID-19, few patients developed chronic cough in spite of a higher proportion of impaired lung function and abnormal lung CT image. Current smoking and digestive symptoms during hospitalization were risk factors for postinfectious cough in COVID-19.

Risk factors for impaired pulmonary diffusion function in convalescent COVID-19 patients: A systematic review and meta-analysis.

Background: The long-term prognosis of COVID-19 survivors remains poorly understood. It is evidenced that the lung is the main damaged organ in COVID-19 survivors, most notably in impairment of pulmonary diffusion function. Hence, we conducted a meta-analysis of the potential risk factors for impaired diffusing capacity for carbon monoxide (DLCO) in convalescent COVID-19 patients. Methods: We performed a systematic search of PubMed, Web of Science, Embase, and Ovid databases for relevant studies from inception until January 7, 2022, limited to papers involving human subjects. Studies were reviewed for methodological quality. Fix-effects and random-effects models were used to pool results. Heterogeneity was assessed using I2. The publication bias was assessed using the Egger's test. PROSPERO registration: CRD42021265377. Findings: A total of eighteen qualified articles were identified and included in the systematic review, and twelve studies were included in the meta-analysis. Our results showed that female (OR: 4.011; 95% CI: 2.928-5.495), altered chest computerized tomography (CT) (OR: 3.002; 95% CI: 1.319-6.835), age (OR: 1.018; 95% CI: 1.007-1.030), higher D-dimer levels (OR: 1.012; 95% CI: 1.001-1.023) and urea nitrogen (OR: 1.004;95% CI: 1.002-1.007) were identified as risk factors for impaired DLCO. Interpretation: Pulmonary diffusion capacity was the most common impaired lung function in recovered patients with COVID-19. Several risk factors, such as female, altered chest CT, older age, higher D-dimer levels and urea nitrogen are associated with impairment of DLCO. Raising awareness and implementing interventions for possible modifiable risk factors may be valuable for pulmonary rehabilitation. Funding: This work was financially supported by Emergency Key Program of Guangzhou Laboratory (EKPG21-29, EKPG21-31), Incubation Program of National Science Foundation for Distinguished Young Scholars by Guangzhou Medical University (GMU2020-207).

Eosinophil Progenitors in Patients With Non-Asthmatic Eosinophilic Bronchitis, Eosinophilic Asthma, and Normal Controls.

Objective: This study aims to explore the potential of in situ airway differentiation of eosinophil progenitors (EoPs) and hematopoietic progenitor cells (HPCs) in sputum and peripheral blood from patients with non-asthmatic eosinophilic bronchitis (NAEB), eosinophilic asthma (EA), and healthy controls (HC). Methods: Using flow cytometry, we enumerated sputum and blood HPCs and EoPs in patients with NAEB (n=15), EA (n=15), and HC (n=14) at baseline. Patients with NAEB and EA were then treated for 1 month with budesonide (200 µg, bid) or budesonide and formoterol (200/6 µg, bid), respectively. HPCs and EoPs in both compartments were re-evaluated. Results: At baseline, NAEB and EA both had significantly greater numbers of sputum but not blood HPCs and EoPs (p<0.05) compared to HC. There were no differences between NAEB and EA. After 1 month of inhaled corticosteroid (ICS) treatment, NAEB patients showed a significant improvement in cough symptoms, but the attenuation of sputum HPC and EoP levels was not significant. Conclusions: NAEB patients have increased airway levels of HPCs and EoPs. One-month treatment with ICS did not fully suppress the level of EoPs in NAEB. Controlling in situ airway differentiation of EoPs may control airway eosinophilia and provide long-term resolution of symptoms in NAEB.

A descending pathway emanating from the periaqueductal gray mediates the development of cough-like hypersensitivity.

Chronic cough is a common refractory symptom of various respiratory diseases. However, the neural mechanisms that modulate the cough sensitivity and mediate chronic cough remain elusive. Here, we report that GABAergic neurons in the lateral/ventrolateral periaqueductal gray (l/vlPAG) suppress cough processing via a descending pathway. We found that l/vlPAG neurons are activated by coughing-like behaviors and that tussive agent-evoked coughing-like behaviors are impaired after activation of l/vlPAG neurons. In addition, we showed that l/vlPAG neurons form inhibitory synapses with the nucleus of the solitary tract (NTS) neurons. The synaptic strength of these inhibitory projections is weaker in cough hypersensitivity model mice than in naïve mice. Important, activation of l/vlPAG GABAergic neurons projecting to the NTS decreases coughing-like behaviors. In contrast, suppressing these neurons enhances cough sensitivity. These results support the notion that l/vlPAG GABAergic neurons play important roles in cough hypersensitivity and chronic cough through disinhibition of cough processing at the medullary level.

Expression of interferon-γ and its effect on cough hypersensitivity in chronic refractory cough patients.

Chronic refractory cough (CRC) is characterised by cough hypersensitivity. Interferon-γ (IFN-γ) has been reported to induce calcium influx, action potentials of vagal neurons in vitro and cough response in guinea pigs. While the effect of IFN-γ in CRC patients remains unknown. Here, via flow-cytometry and inhalation cough challenge, we found CRC patients had significantly increased levels of sputum IFN-γ+CD4+ T cells, IFN-γ+CD8+ T cells as well as supernatant of IFN-γ. The average number of coughs in CRC patients increased as the concentration of inhaled IFN-γ went up in IFN-γ cough challenge. Two or more coughs and five or more coughs elicited by inhaled IFN-γ in CRC patients occurred in 7 of 10 and 2 of 10, respectively. Preinhaled IFN-γ (100 µg/mL) increased the capsaicin cough sensitivity in CRC patients but not healthy volunteers. Targeting IFN-γ may be a potential effective anti-tussive strategy in CRC patients.

Green Preparation of Robust Hydrophobic ß-Cyclodextrin/Chitosan Sponges for Efficient Removal of Oil from Water.

A relatively straightforward green method to fabricate robust hydrophobic sponges for effective removal of oil pollutants and other organic contaminants was developed. These sponges were constructed from bio-sources: citronellal and palmitic acid-modified aminoethyl cyclodextrin-sodium phytate-chitosan (ACCTCS). The modified sponge exhibited desirable mechanical properties and strong hydrophobicity with a water contact angle (WCA) of 147.8°. Scanning electron microscopy showed that the ACCTCS sponge had a highly porous structure that was particularly suitable for organic component absorption. The sponge exhibited excellent absorption capacities for n-hexane, trichloromethane, vacuum pump oil, and peanut oil (47.9, 32.3, 32.6, and 32.2 g/g, respectively). The removal rate of oil was more than 80% (>26.2 g/g) after 10 absorption-desorption cycles. The ACCTCS sponge also showed good oil/water and organic components/water separation performance. The bio-source materials, green preparation method, and new absorbed-oil recovery strategy provided a novel pathway to construct multifunctional absorbents for oil/water separation in industrial wastewater.