Coughing our guts up: how do we diagnose reflux cough?

Should Peptest be routinely used in a cough clinic? The answer is yes, but only as part of more intricate workup in which discovering the nature of the reflux is as important as identifying its presence. https://bit.ly/3QkbChb.

The volatile oil of Hyssopus cuspidatus Boriss. (HVO) ameliorates OVA-induced allergic asthma via inhibiting PI3K/Akt/JNK/P38 signaling pathway and maintaining airway barrier integrity.

ETHNOPHARMACOLOGICAL RELEVANCE: Hyssopus cuspidatus Boriss., a classic Uyghur medicine, is used to treat inflammatory lung diseases such as asthma. But the therapeutic effect and mechanism of the volatile oil of Hyssopus cuspidatus Boriss.(HVO) in asthma therapy remain unclear. AIM OF THE STUDY: We aim to characterize the constituents of HVO, investigate the therapeutic effect in OVA-induced allergic asthmatic mice and further explore the molecular mechanism. MATERIALS AND METHODS: In this study, we applied two-dimensional gas chromatography quadrupole time-of-flight mass spectrometry (GC × GC-QTOF MS) to identify the ingredients of HVO. We established OVA-induced asthmatic model to investigate the therapeutic effect of HVO. To further explore the potential molecular pathways, we used network pharmacology approach to perform GO and KEGG pathways enrichment, and then built an ingredient-target-pathway network to identify key molecular pathways. Finally, LPS-induced RAW 264.7 macrophages and OVA-induced asthmatic model were used to validate the potential signaling pathways. RESULTS: GC × GC-QTOF MS analysis revealed the presence of 123 compounds of HVO. The sesquiterpenes and monoterpenes are the main constituents. The in vivo study indicated that HVO suppressed OVA-induced eosinophilic infiltration in lung tissues, inhibited the elevation of IgE, IL-4, IL-5, and IL-13 levels, downregulated the expressions of phosphorylated PI3K, Akt, JNK and P38, and maintained epithelial barrier integrity via reducing the degradation of occludin, Zo-1, Zo-2, and E-cadherin. The in vitro study also revealed an inhibition of NO release and downregulation of phosphorylated PI3K, Akt, JNK and P38 levels. CONCLUSION: HVO alleviates airway inflammation in OVA-induced asthmatic mice by inhibiting PI3K/Akt/JNK/P38 signaling pathway and maintaining airway barrier integrity via reducing the degradation of occludin, Zo-1, Zo-2, and E-cadherin.

Protective effect of vitexin against high fat-induced vascular endothelial inflammation through inhibiting trimethylamine N-oxide-mediated RNA m6A modification.

A high-fat diet (HFD) is a major risk factor for cardiovascular disease. However, the specific effects of a HFD on vascular inflammation and the protective role of vitexin, a bioactive compound derived from food, require further research. This study investigated the protective effects of vitexin intervention against HFD-induced vascular inflammation and its underlying mechanism. The results demonstrated that vitexin intervention significantly reduced body weight, serum total cholesterol, and low-density lipoprotein cholesterol levels in HFD-fed mice. Vitexin also improved vascular pathological changes and the inflammatory status in the mice. Furthermore, vitexin intervention reduced serum TMAO levels in HFD-fed mice by altering the gut microbiota composition. The HFD significantly increased N6-methyladenosine (m6A) levels in aorta tissues, while vitexin intervention reversed this abnormal m6A level. Through metabolite affinity responsive target fluorescence quenching and molecular docking assays, it was found that vitexin could directly bind to fat mass and obesity-associated protein (FTO), potentially promoting m6A demethylation. The dose-response relationship between TMAO and inflammation/m6A was further validated in HUVEC cells and in vivo mouse experiments. Specifically, TMAO increased m6A levels and inflammation, while vitexin inhibited TMAO-mediated m6A modification, exhibiting anti-inflammatory effects. In conclusion, this study demonstrates the protective role of vitexin against HFD-induced vascular inflammation by inhibiting TMAO-mediated RNA m6A modification, laying the foundation for the development of functional foods.

Nonlinear responses of biofilm bacteria to alkyl-chain length of parabens by DFT calculation.

Parabens can particularly raise significant concerns regarding the disruption of microbial ecology due to their antimicrobial properties. However, the responses of biofilm bacteria to diverse parabens with different alkyl-chain length remains unclear. Here, theoretical calculations and bioinformatic analysis were performed to decipher the influence of parabens varying alkyl-chain lengths on the biofilm bacteria. Our results showed that the disturbances in bacterial community did not linearly response to the alkyl-chain length of parabens, and propylparaben (PrP), with median chain length, had more severe impact on bacterial community. Despite the fact that paraben lethality linearly increased with chain length, the PrP had a higher chemical reactions potential than parabens with shorter or longer alkyl-chain. The chemical reactions potential was critical in the nonlinear responses of bacterial community to alkyl-chain length of parabens. PrP could impose selective pressure to disturb the bacterial community, because it had a more profound contribution to deterministic assembly process. Furthermore, N-acyl-homoserine lactones was also significantly promoted under PrP exposure, confirming that PrP could affect the bacterial community by influencing the quorum-sensing system. Overall, our study reveals the nonlinear responses of bacterial communities to the alkyl-chain lengths of parabens and provides insightful perspectives for the better regulation of parabens. ENVIRONMENTAL IMPLICATION: Parabens are recognized as emerging organic pollutants, which specially raise great concerns due to their antimicrobial properties disturbing microbial ecology. However, few study have addressed the relationship between bacterial community responses and the molecular structural features of parabens with different alkyl-chain length. This investigation revealed nonlinear responses of the bacterial community to the alkyl-chain length of parabens through DFT calculation and bioinformatic analysis and identified the critical roles of chemical reactions potential in nonlinear responses of bacterial community. Our results benefit the precise evaluation of ecological hazards posed by parabens and provide useful insights for better regulation of parabens.

Vertically Oriented Perovskites with Minimized Intrinsic Boundaries for Efficient Photovoltaics.

Intrinsic boundaries formed by grain stacks of randomly oriented perovskite crystallites seriously restrict charge transport in the resultant photovoltaic devices, whereas direct passivation of these defects remains unexplored, and it is desirable to modulate perovskite growth with uniform orientation. Herein, we report a simple but effective method to regulate perovskite crystallization by employing a volatile and polymerizable monomer of hydroxyethyl methacrylate (HEMA), which can simultaneously interact with both FA+ and Pb2+ via hydrogen and coordination bonding, respectively, to seed perovskite crystallization with accelerated nucleation and retarded crystal growth. Upon thermal annealing, the gradual volatilization and partial self-condensation of the HEMA drive the perovskite growth perpendicularly to the substrate, leading to largely suppressed defect states, improved crystallinity, and a reduced Young's modulus of the perovskite film. As a result, champion efficiencies exceeding 24 and 22% with improved operational and mechanical stability of the optimized perovskite solar cells based on rigid and flexible substrates were finally achieved.

A Smartphone-Based M-Health Monitoring System for Arrhythmia Diagnosis.

Deep learning technology has been widely adopted in the research of automatic arrhythmia detection. However, there are several limitations in existing diagnostic models, e.g., difficulties in extracting temporal information from long-term ECG signals, a plethora of parameters, and sluggish operation speed. Additionally, the diagnosis performance of arrhythmia is prone to mistakes from signal noise. This paper proposes a smartphone-based m-health system for arrhythmia diagnosis. First, we design a cycle-GAN-based ECG denoising model which takes real-world noise signals as input and aims to produce clean ECG signals. In order to train its two generators and two discriminators simultaneously, we explore an unsupervised pre-training strategy to initialize the generator and accelerate the convergence speed during training. Second, we propose an arrhythmia diagnosis model based on the time convolution network (TCN). This model can identify 34 common arrhythmia events using eight-lead ECG signals, and we deploy such a model on the Android platform to develop an at-home ECG monitoring system. Experimental results have demonstrated that our approach outperforms the existing noise reduction methods and arrhythmia diagnosis models in terms of denoising effect, recognition accuracy, model size, and operation speed, making it more suitable for deployment on mobile devices for m-health monitoring services.

Revealing bioresponses of biofilm and flocs to salinity gradient in halophilic biofilm reactor.

Understanding the different biological responses to salinity gradient between coexisting biofilm and flocs is crucial for regulating the ecological function of biofilm system. This study investigated performance, dynamics, and community assembly of biofilm system under 3 %-7% salinity gradient. The removal efficiency of NH4+-N remained stable and exceeded 93 % at 3 %-6% salinity, but decreased to below 80 % at 7 % salinity. The elevated salinity promoted the synthesis of extracellular polymer substrates, inhibited microbial respiration, and significantly regulated the microbial community structure. Compared to flocs, biofilm exhibited greater species diversity and richer Nitrosomonas. It was found diffusion limitations dominated the microbial community assembly under the salinity gradient. And microbial network revealed positive interactions predominated the microbial relationships, designating norank Spirochaetaceae, unclassified Micrococcales, Corynebacterium, and Pusillimonas as keystone species. Moreover, distinct salinity preferences in nitrogen transformation-related genes were observed. This study can improve the understanding to the regulation of biofilm systems to salt stresses.

Advancements in Stimulus-Responsive Co-Delivery Nanocarriers for Enhanced Cancer Immunotherapy.

Cancer immunotherapy has emerged as a novel therapeutic approach against tumors, with immune checkpoint inhibitors (ICIs) making significant clinical practice. The traditional ICIs, PD-1 and PD-L1, augment the cytotoxic function of T cells through the inhibition of tumor immune evasion pathways, ultimately leading to the initiation of an antitumor immune response. However, the clinical implementation of ICIs encounters obstacles stemming from the existence of an immunosuppressive tumor microenvironment and inadequate infiltration of CD8+T cells. Considerable attention has been directed towards advancing immunogenic cell death (ICD) as a potential solution to counteract tumor cell infiltration and the immunosuppressive tumor microenvironment. This approach holds promise in transforming "cold" tumors into "hot" tumors that exhibit responsiveness to antitumor. By combining ICD with ICIs, a synergistic immune response against tumors can be achieved. However, the combination of ICD inducers and PD-1/PD-L1 inhibitors is hindered by issues such as poor targeting and uncontrolled drug release. An advantageous solution presented by stimulus-responsive nanocarrier is integrating the physicochemical properties of ICD inducers and PD-1/PD-L1 inhibitors, facilitating precise delivery to specific tissues for optimal combination therapy. Moreover, these nanocarriers leverage the distinct features of the tumor microenvironment to accomplish controlled drug release and regulate the kinetics of drug delivery. This article aims to investigate the advancement of stimulus-responsive co-delivery nanocarriers utilizing ICD and PD-1/PD-L1 inhibitors. Special focus is dedicated to exploring the advantages and recent advancements of this system in enabling the combination of ICIs and ICD inducers. The molecular mechanisms of ICD and ICIs are concisely summarized. In conclusion, we examine the potential research prospects and challenges that could greatly enhance immunotherapeutic approaches for cancer treatment.

Electrochemical oxidative decarboxylative of α-oxocarboxylic acids towards the synthesis of quinazolines and quinazolinones.

A mild and environmentally electrochemical method for the synthesis of quinazolines and quinazolinones has been developed through anodic oxidation decarboxylative of α-oxocarboxylic acids. The present reaction was efficiently conducted by using simple and cheap NH4I as the N-source and electrolyte in an undivided cell. The desired products, quinazolines and quinazolinones, were isolated in high yield under chemical oxidant free conditions.

Recovery mechanism of heterotrophic ammonia assimilation system under chromium hexavalent stress.

Heterotrophic ammonia assimilation (HAA), an innovative technology for high-salinity wastewater treatment, demonstrates self-recovery capability following Cr (VI) stress. This study investigated the inhibitory effects and self-restoration mechanisms of Cr (VI) at various stress levels. The removal efficiencies of NH4+-N and Cr (VI) in the HAA gradually decreased with increasing influent Cr (VI) concentration. Exposure to Cr (VI) increased the amounts of high-molecular-weight proteins in soluble microbial products and stimulated the generation of extracellular polymeric substances. Heterotrophic functional microorganisms with Cr (VI) tolerance, such as Marinobacter and Planktosalinus, were enriched. An assimilation pathway gene (glnA) and a Cr (VI)-related gene (atoB) were also upregulated. After ceasing Cr (VI) addition, the HAA system demonstrated a 17.1 % increase in the removal efficiency of NH4+-N, which was attributable to its self-recovery ability. This study provides a scientific and theoretical foundation for the HAA process in resisting the impact of heavy-metal-containing wastewater and self-recovery.

Catalytic oxidation of toluene by manganese oxides: Effect of K+ doping on oxygen vacancy.

Alkali metal potassium was beneficial to the electronic regulation and structural stability of transition metal oxides. Herein, K ions were introduced into manganese oxides by different methods to improve the degradation efficiency of toluene. The results of activity experiments indicated that KMnO4-HT (HT: Hydrothermal method) exhibited outstanding low-temperature catalytic activity, and 90% conversion of toluene can be achieved at 243°C, which was 41°C and 43°C lower than that of KNO3-HT and Mn-HT, respectively. The largest specific surface area was observed on KMnO4-HT, facilitating the adsorption of toluene. The formation of cryptomelane structure over KMnO4-HT could contribute to higher content of Mn3+ and lattice oxygen (Olatt), excellent low-temperature reducibility, and high oxygen mobility, which could increase the catalytic performance. Furthermore, two distinct degradation pathways were inferred. Pathway Ⅰ (KMnO4-HT): toluene → benzyl → benzoic acid → carbonate → CO2 and H2O; Pathway ⅠⅠ (Mn-HT): toluene → benzyl alcohol → benzoic acid → phenol → maleic anhydride → CO2 and H2O. Fewer intermediates were detected on KMnO4-HT, indicating its stronger oxidation capacity of toluene, which was originated from the doping of K+ and the interaction between KOMn. More intermediates were observed on Mn-HT, which can be attributed to the weaker oxidation ability of pure Mn. The results indicated that the doping of K+ can improve the catalytic oxidation capacity of toluene, resulting in promoted degradation of intermediates during the oxidation of toluene.

Coexistence of giant Goos-Hänchen shift and high reflectance in Dirac semimetal based multilayered structure.

Bulk Dirac semimetals (BDSs) possess Fermi energy dependent optical parameters, providing unprecedented opportunities for the study of the controllable Goos-Hänchen (GH) shift. However, the enhancement of GH shifts often comes at the cost of the reflectance in the previous BDS-based structures, which hinders their practical application. In this work, we theoretically present the investigation of the GH shift in a multilayered structure composed of one BDS film and a symmetric one-dimensional photonic crystal (1DPC) with a defect layer. We demonstrate that this well-designed structure supports a large GH shift at the specific working wavelength, whose magnitude can be enhanced up to 3883 times the incident wavelength. In particular, such an enhanced GH shift achieved in this structure is associated with high reflectance (0.94) and these remarkable features can be attributed to the sharp change in the reflective phase and the destructive interference that occurs between the simultaneously excited optical Tamm state (OTS) at the BDS/1DPC interface and the defect state at the 1D defected PC. In addition, we also explore the manipulation of the GH shift by adjusting the Fermi energy of the BDS as well as the geometrical parameter of the multilayered structure. Our results provide a new approach for realizing an enhanced and controllable GH shift in a BDS-based multilayered structure, which endows it with promising prospects for application in optical sensors, optical detectors and beam controllers.

Nutrients recovery by coupled bioreactor of heterotrophic ammonia assimilation and microbial fuel cell in saline wastewater.

Heterotrophic ammonia assimilation (HAA) process had been widely used in the treatment of high salt wastewater, but the electro enhanced coupling process and electron transfer process were rarely studied. In this study, a HAA process coupled microbial fuel cell (MFC) system was established to treat ammonia-containing wastewater under increasing salinity to achieve nitrogen recovery and electricity generation. Up to 95.4 % NH4+-N and 96.4 % COD removal efficiencies were achieved at 2 % salinity in HAA-MFC. The maximum power density and current density at 2 % salinity were 29.93 mW/m2 and 182.37 mA/m2, respectively. The residual organic matter in the cathode effluent was effectively removed by the anode. The increase of salinity not only enhanced the sludge settling performance and activity, but also promoted the enzyme activity and amino acid production of the ammonia assimilation pathway. Marinobacter and Halomonas were gradually enriched at the anode and cathode with increased salinity to promote ammonia assimilation and electron production. This research offered a promising solution to overcome salinity-related challenges in wastewater treatment and resource recovery.

Effective substances and molecular mechanisms guided by network pharmacology: An example study of Scrophulariae Radix treatment of hyperthyroidism and thyroid hormone-induced liver and kidney injuries.

ETHNOPHARMACOLOGICAL RELEVANCE: Scrophulariae Radix (Xuanshen [XS]) has been used for several years to treat hyperthyroidism. However, its effective substances and pharmacological mechanisms in the treatment of hyperthyroidism and thyroid hormone-induced liver and kidney injuries have not yet been elucidated. AIM OF THE STUDY: This study aimed to explore the pharmacological material basis and potential mechanism of XS therapy for hyperthyroidism and thyroid hormone-induced liver and kidney injuries based on network pharmacology prediction and experimental validation. MATERIALS AND METHODS: Based on 31 in vivo XS compounds identified using ultra-performance liquid chromatography tandem quadruple exactive orbitrap high-resolution accurate-mass spectrometry (UPLC-QE-HRMS), a network pharmacology approach was used for mechanism prediction. Systematic networks were constructed to identify the potential molecular targets, biological processes (BP), and signaling pathways. A component-target-pathway network was established. Mice were administered levothyroxine sodium through gavage for 30 d and then treated with different doses of XS extract with or without propylthiouracil (PTU) for 30 d. Blood, liver, and kidney samples were analyzed using an enzyme-linked immunosorbent assay (ELISA) and western blotting. RESULTS: A total of 31 prototypes, 60 Phase I metabolites, and 23 Phase II metabolites were tentatively identified in the plasma of rats following the oral administration of XS extract. Ninety-six potential common targets between the 31 in vivo compounds and the diseases were identified. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that Bcl-2, BAD, JNK, p38, and ERK1/2 were the top targets. XS extract with or without PTU had the following effects: inhibition of T3/T4/fT3/fT4 caused by levothyroxine; increase of TSH levels in serum; restoration of thyroid structure; improvement of liver and kidney structure and function by elevating the activities of anti-oxidant enzymes catalase (CAT),superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px); activation anti-apoptotic proteins Bcl-2; inhibition the apoptotic protein p-BAD; downregulation inflammation-related proteins p-ERK1/2, p-JNK, and p-p38; and inhibition of the aggregation of pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6, as well as immune cells in the liver. CONCLUSION: XS can be used to treat hyperthyroidism and liver and kidney injuries caused by thyroid hormones through its anti-oxidant, anti-inflammatory, and anti-apoptotic properties. In addition, serum pharmacochemical analysis revealed that five active compounds, namely 4-methylcatechol, sugiol, eugenol, acetovanillone, and oleic acid, have diverse metabolic pathways in vivo and exhibit potential as effective therapeutic agents.

Role of alveolar nitric oxide in gastroesophageal reflux-associated cough: prospective observational study.

BACKGROUND: Fractional exhaled nitric oxide (FeNO) measured at multiple exhalation flow rates can be used as a biomarker to differentiate central and peripheral airway inflammation. However, the role of alveolar nitric oxide (CaNO) indicating peripheral airway inflammation remains unclear in gastroesophageal reflux-associated cough (GERC). OBJECTIVES: We aimed to characterize the changes in alveolar nitric oxide (CaNO) and determine its clinical implication in GERC. DESIGN: This is a single-center prospective observational study. METHODS: FeNOs at exhalation flow rates of 50 and 200 ml/s were measured in 102 patients with GERC and 134 patients with other causes of chronic cough (non-GERC). CaNO was calculated based on a two-compartment model and the factors associated with CaNO were analyzed. The effect of anti-reflux therapy on CaNO was examined in 26 GERC patients with elevated CaNO. RESULTS: CaNO was significantly elevated in GERC compared with that in non-GERC (4.6 ± 4.4 ppb versus 2.8 ± 2.3 ppb, p < 0.001). GERC patients with high CaNO (>5 ppb) had more proximal reflux events (24 ± 15 versus 9 ± 9 episodes, p = 0.001) and a higher level of pepsin (984.8 ± 492.5 versus 634.5 ± 626.4 pg/ml, p = 0.002) in sputum supernatant than those with normal CaNO. More GERC patients with high CaNO required intensified anti-reflux therapy (χ2 = 3.963, p = 0.046), as predicted by a sensitivity of 41.7% and specificity of 83.3%. Cough relief paralleled a significant improvement in CaNO (8.3 ± 3.0 versus 4.8 ± 2.6 ppb, p < 0.001). CONCLUSION: Peripheral airway inflammation can be assessed by CaNO measurement in GERC. High CaNO indicates potential micro-aspiration and may predict a necessity for intensified anti-reflux therapy.

Role of CaNO in GERCWhy was the study done? This study aimed to investigate the role of concentration of alveolar nitric oxide (CaNO) as a biomarker for peripheral airway inflammation in patients with gastroesophageal reflux-associated cough (GERC). The evaluation of airway inflammation in GERC has not been widely practiced in clinical settings, and the potential of CaNO as a biomarker remained unclear.What did the researchers do? The researchers conducted a prospective study involving patients diagnosed with GERC and compared the changes in CaNO levels between GERC patients and those with cough due to other causes. The study also identified potential factors contributing to elevated CaNO levels in GERC patients relative to the normal range. Additionally, CaNO level changes were evaluated in a subgroup of GERC patients with initially elevated CaNO levels (n = 26).What did the researchers find? The study found that CaNO levels were significantly increased in GERC patients. Using a reference value for normal CaNO, the GERC patients were divided into a high CaNO cohort and a normal CaNO cohort. More proximal reflux episodes and higher level of pepsin in sputum supernatant were observed in the high CaNO cohort. Moreover, CaNO demonstrated moderate predictive value for the therapeutic efficacy of intensified anti-reflux therapy in GERC patients. After several weeks of anti-reflux therapy, CaNO levels significantly decreased along with the resolution of cough. These findings further confirmed the predictive value of CaNO for anti-reflux therapy.What do the findings mean? The findings suggest that CaNO may have the potential to be used as a non-invasive biomarker for detecting peripheral airway inflammation in GERC patients. Increased CaNO may be associated with potential micro-aspiration. Furthermore, high CaNO may predict the need for intensified anti-reflux therapy.

Enhanced mechanical properties and antibacterial activities of chitosan films through incorporating zein-gallic acid conjugate stabilized cinnamon essential oil Pickering emulsion.

In this study, zein-gallic acid covalent complex prepared by alkali treatment was utilized as an emulsifier to stabilize cinnamon essential oil (CEO) Pickering emulsion, and the chitosan-based (CZGE) films loaded with CEO Pickering emulsion were prepared by blending. The influences of different contents of CEO Pickering emulsion on the physical properties and biological activities of CZGE films were investigated. The results showed that Pickering emulsion had good compatibility with chitosan matrix and enhanced the interaction between film-forming matrix polymer. In addition, incorporating with CEO Pickering emulsion (15 %, v/v) significantly improved the mechanical and barrier properties of the films, and also enhanced the light transmittance and thermal stability of the films. Furthermore, the loading of emulsion also improved the antioxidant activities of the films and led to the formation of high antimicrobial property against food pathogens, and the slow-release behavior of CEO could effectively extend the biological activity of the films. These results suggested that Pickering emulsion has potential as a loading system and a plasticizer in active packaging, and the feasibility of CZGE film in food packaging.

Contributions of climate change and human activities to grassland degradation and improvement from 2001 to 2020 in Zhaosu County, China.

Grassland degradation poses a serious threat to biodiversity, ecosystem services, and human well-being. In this study, we investigated grassland degradation in Zhaosu County, China, between 2001 and 2020, and analyzed the impacts of climate change and human activities using the Miami model. The actual net primary productivity (ANPP) obtained with CASA (Carnegie-Ames-Stanford Approach) modeling, showed a decreasing trend, reflecting the significant degradation that the grasslands in Zhaosu County have experienced in the past 20 years. Grassland degradation was found to be highest in 2018, while the degraded area continuously decreased in the last 3 years (2018-2020). Climatic factors for found to be the dominant factor affecting grassland degradation, particularly the decrease in precipitation. On the other hand, human activities were found to be the main factor affecting improvement of grasslands, especially in recent years. This finding profoundly elucidates the underlying causes of grassland degradation and improvement and helps implement ecological conservation and restoration measures. From a practical perspective, the research results provide an important reference for the formulation of policies and management strategies for sustainable land use.

New Insights Into Refractory Chronic Cough and Unexplained Chronic Cough: A 6-Year Ambispective Cohort Study.

PURPOSE: Only limited studies have depicted the unique features and management of refractory chronic cough (RCC) and unexplained chronic cough (UCC). These led to the initiation of this study, which reported the demographic characteristics, manifestations, and long-term outcomes on a large series of consecutive RCC/UCC patients, providing a guideline-led real-world clinical experience. METHODS: Retrospective baseline information was obtained from Clinical Research Database (January 2016 to May 2021). At least 6 months after the last clinic visit, included subjects were prospectively followed up. RESULTS: Three hundred and sixty-nine RCC and UCC patients (199 females, 53.9%) were analyzed. The median cough duration was 24.0 (12.0-72.0) months. Laryngeal symptoms were reported in 95.9% of the patients. The common triggers for coughing were talking (74.9%), pungent odors (47.3%), eating (45.5%), and cold air (42.8%). RCC was considered in 38.2%, and the remainder of 228 patients had UCC, with an equal sex distribution (P = 0.66). Among the 141 RCCs, 90.8% (128) had refractory reflux cough, which was more responsive to current treatments (P < 0.01). Although most features and test results between RCC and UCC were similar, UCC was more commonly inappropriately treated (P < 0.01). Nineteen (7.7-41.1) months after the final clinic visit, 31.2% still coughed persistently, while 68.8% reported cough improvement or remission. RCC reported more favorable treatment outcomes (including cough improvement, control, and spontaneous remission) than UCC (P < 0.01). Coughs with long duration before the initial cough clinic visit (P < 0.01), frequent urinary incontinence (P < 0.01), and being sensitive to "talking" (P < 0.01) or "cold air" (P < 0.01) were less likely to be solved. CONCLUSIONS: The current treatments only improve cough symptoms in two-thirds of patients. Clinical indicators for treatment failure were those coughing for long duration and being sensitive to "talking" or "cold air."