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Chronic obstructive pulmonary disease (COPD), which includes emphysema and chronic bronchitis, is now the third cause of death worldwide, and COVID-19 infection has been reported as an exacerbation factor of them. In this study, we report that the intratracheal administration of the keratan sulfate-based disaccharide L4 mitigates the symptoms of elastase-induced emphysema in a mouse model. To know the molecular mechanisms, we performed a functional analysis of a C-type lectin receptor, langerin, a molecule that binds L4. Using mouse BMDCs (bone marrow-derived dendritic cells) as langerin-expressing cells, we observed the downregulation of IL-6 and TNFa and the upregulation of IL-10 after incubation with L4. We also identified CapG (a macrophage-capping protein) as a possible molecule that binds langerin by immunoprecipitation combined with a mass spectrometry analysis. We identified a portion of the CapG that was localized in the nucleus and binds to the promoter region of IL-6 and the TNFa gene in BMDCs, suggesting that CapG suppresses the gene expression of IL-6 and TNFa as an inhibitory transcriptional factor. To examine the effects of L4 in vivo, we also generated langerin-knockout mice by means of genome editing technology. In an emphysema mouse model, the administration of L4 did not mitigate the symptoms of emphysema as well as the inflammatory state of the lung in the langerin-knockout mice. These data suggest that the anti-inflammatory effect of L4 through the langerin-CapG axis represents a potential therapeutic target for the treatment of emphysema and COPD. [ABSTRACT FROM AUTHOR]

Cigarette smoke (CS)-induced oxidative stress drives the pathogenesis of respiratory diseases, in which the activation and accumulation of reactive oxygen species (ROS) play an important role. Ferroptosis, a regulated cell death induced by Fe2+-dependent, lipid peroxidation, and ROS, is closely related to CS-induced airway injury disease, but its mechanism remains unclear. We found that bronchial epithelial ferroptosis and expression of iNOS in smoking patients were significantly higher than that in non-smokers. The iNOS, induced by CS exposure, was involved in bronchial epithelial cell ferroptosis, whereas genetic depletion or pharmacologic inactivation of iNOS attenuated the CS-induced ferroptosis and mitochondrial dysfunction. Our mechanistic studies found that SIRT3 directly bound to and negatively regulated iNOS to mediate ferroptosis. Moreover, we found that the Nrf-2/SIRT3 signal was deactivated by cigarette smoke extract (CSE)-induced ROS. Collectively, these results linked CS to human bronchial epithelial cell ferroptosis through ROS deactivation of the Nrf-2/SIRT3 signal to promote iNOS expression. Our study provides new insights into the pathogenesis of CS-induced tracheal injury diseases such as chronic bronchitis, emphysema, and chronic obstructive pulmonary disease. • Human lung tissues are used to confirm that cigarette smoke induces ferroptosis in bronchial epithelium. • ROS is a key factor in the bronchial epithelium ferroptosis caused by cigarette smoke. • Activation of Nrf-2/SIRT3 inhibits ferroptosis in the bronchial epithelium. • Inactivating iNOS inhibits ferroptosis in the bronchial epithelium. • SIRT3 binds directly to iNOS and inhibits its expression and activity. [ABSTRACT FROM AUTHOR]

Among individuals with chronic respiratory conditions, transitions between patterns of tobacco product use are not well understood. This study examines how transitions, including quitting altogether, differ over time between those who do and do not have chronic respiratory conditions. Data from youth and adult participants of the longitudinal Population Assessment of Tobacco and Health Study (2013–2018) were analyzed. Youth aged 12–17 years were included if they had aged into the adult sample by Wave 4. Stratified polytomous regression models built under a first-order Markov assumption modeled the probability of transitioning between different states/patterns of tobacco product use (exclusive current E-cigarette use, exclusive current combustible tobacco product use, current dual use of combustible products and E-cigarettes, and no current tobacco product use) at each wave. Marginal transition probabilities were computed as a function of ever or past-year diagnosis of a respiratory condition (separately for asthma and a composite variable representing chronic bronchitis, emphysema, and/or chronic obstructive pulmonary disease). Analyses were conducted in 2020–2021. Most individuals, regardless of respiratory condition, maintained the same pattern of tobacco use between waves. Exclusive combustible tobacco product users, including those with or without a respiratory condition, were not likely to become exclusive E-cigarette users or to quit using tobacco entirely. Although combustible tobacco use negatively impacts the management and prognosis of respiratory illnesses, combustible tobacco users who were recently diagnosed with a chronic respiratory condition were not likely to quit using tobacco. Efforts to encourage and support cessation in this medically vulnerable population should be increased. [ABSTRACT FROM AUTHOR]

Ground-level ozone ranks sixth among common air pollutants. It worsens lung diseases like asthma, emphysema, and chronic bronchitis. Despite recent attention from researchers, the link between exhaled breath and ozone-induced injury remains poorly understood. This study aimed to identify novel exhaled biomarkers in ozone-exposed mice using ultra-sensitive photoinduced associative ionization time-of-flight mass spectrometry and machine learning. Distinct ion peaks for acetonitrile (m/z 42, 60, and 78), butyronitrile (m/z 70, 88, and 106), and hydrogen sulfide (m/z 35) were detected. Integration of tissue characteristics, oxidative stress-related mRNA expression, and exhaled breath condensate free-radical analysis enabled a comprehensive exploration of the relationship between ozone-induced biological responses and potential biomarkers. Under similar exposure levels, C57BL/6 mice exhibited pulmonary injury characterized by significant inflammation, oxidative stress, and cardiac damage. Notably, C57BL/6 mice showed free radical signals, indicating a distinct susceptibility profile. Immunodeficient non-obese diabetic Prkdc -/-/ Il2rg -/- (NPI) mice exhibited minimal biological responses to pulmonary injury, with little impact on the heart. These findings suggest a divergence in ozone-induced damage pathways in the two mouse types, leading to alterations in exhaled biomarkers. Integrating biomarker discovery with comprehensive biopathological analysis forms a robust foundation for targeted interventions to manage health risks posed by ozone exposure. [Display omitted] • PAI-TOFMS detects exhaled biomarkers of ozone-exposed mice with high sensitivity. • The impact of ozone varies distinctly between the heart and lungs in mice. • The immune responses are vital in ozone-related damage. • Free radicals in EBC are linked to ozone exposure and immune responses. • Exhaled breath analysis is a promising tool for monitoring ozone exposure. [ABSTRACT FROM AUTHOR]

• Formation of mucus plugs has been observed in critically ill COVID-19 patients. • Proteomic analyses of airway mucus were obtained by bronchoscopy or induced sputum. • Eight proteins specifically present in COVID-19 were found compared with chronic obstructive pulmonary disease and asthma. The mortality rate for critically ill COVID-19 cases was more than 80%. Nonetheless, research about the effect of common respiratory diseases on critically ill COVID-19 expression and outcomes is scarce. We performed proteomic analyses on airway mucus obtained by bronchoscopy from patients with severe COVID-19, or induced sputum from patients with chronic obstructive pulmonary disease (COPD), asthma, and healthy controls. Of the total identified and quantified proteins, 445 differentially expressed proteins (DEPs) were found in different comparison groups. In comparison with COPD, asthma, and controls, 11 proteins were uniquely present in COVID-19 patients. Apart from DEPs associated with COPD versus controls and asthma versus controls, there was a total of 59 DEPs specific to COVID-19 patients. Finally, the findings revealed that there were 8 overlapping proteins in COVID-19 patients, including C9, FGB, FGG, PRTN3, HBB, HBA1, IGLV3-19, and COTL1. Functional analyses revealed that most of them were associated with complement and coagulation cascades, platelet activation, or iron metabolism, and anemia-related pathways. This study provides fundamental data for identifying COVID-19–specific proteomic changes in comparison with COPD and asthma, which may suggest molecular targets for specialized therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Evidence on the association of volatile organic compounds (VOCs) with chronic bronchitis (CB) and emphysema is spare and defective. To evaluate the relationship between urinary metabolites of VOCs (mVOCs) with CB and emphysema, and to identify the potential mVOC of paramount importance, data from NHANES 2011–2014 waves were utilized. Logistic regression was conducted to estimate the independent association of mVOCs with respiratory outcomes. Least absolute shrinkage and selection operator (LASSO) regression was performed to screen a parsimonious set of CB- and emphysema-relevant mVOCs that were used for further co-exposure analyses of weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR). Mediation analysis was employed to detect the mediating role of inflammatory makers in such associations. In single exposure analytic model, nine mVOCs were individually and positively associated with CB, while four mVOCs were with emphysema. In WQS regression, positive association between LASSO selected mVOCs and CB was identified (OR = 1.82, 95% CI : 1.25 to 2.69), and N-acetyl-S-(4-hydroxy-2-butenyl)- l -cysteine (MHBMA3) weighted the highest. Results from BKMR further validated such combined association and the significance of MHBMA3. As for emphysema, significantly positive overall trend of mVOCs was only observed in BKMR model and N-acetyl-S-(N-methylcarbamoyl)- l -cysteine (AMCC) contributed most to the mixed effect. White blood cell count (WBC) and lymphocyte number (LYM) were mediators in the positive pattern of mVOCs mixture with CB, while association between mVOCs mixture and emphysema was significantly mediated by LYM and segmented neutrophils num (NEO). This study demonstrated that exposure to VOCs was associated with CB and emphysema independently and combinedly, which might be partly speculated that VOCs were linked to activated inflammations. Our findings shed novel light on VOCs related respiratory illness, and provide a new basis for the contribution of certain VOCs to the risk of CB and emphysema, which has potential public health implications. [Display omitted] • Metabolites of volatile organic compounds co-exposure were positively associated with chronic bronchitis and emphysema. • MHBMA3, the metabolite of 1,3-butadiene, was the major contributor to increased CB. • AMCC, the metabolite of methyl isocyanate, drove the main effect of the mVOCs mixture on elevated emphysema risk. • Lymphocyte number (LYM) and white blood cell count were mediators in the association of mVOCs with CB. • The relationship between mVOCs and emphysema was markedly mediated by LYM and segmented neutrophils num. [ABSTRACT FROM AUTHOR]

[Display omitted] • ELP treatment attenuates airway inflammation and obstruction in lipopolysaccharide-induced chronic bronchitis rat. • ELP treatment improves metabolic pathway changes that caused by LPS challenge. • ELP could inhibit the TLR4 signaling pathways in LPS-induced Beas-2B cells and CB rats. Chronic bronchitis (CB), a type of chronic obstructive pulmonary disease (COPD), poses a significant global health burden owing to its high morbidity and mortality rates. Eucalyptol, limonene and pinene enteric capsules (ELPs) are clinically used as expectorants to treat various respiratory diseases, including CB, but their acting mechanisms remain unclear. In this study, we investigated the anti-CB effects of ELP in a rat model of lipopolysaccharide (LPS)-induced CB. The molecular mechanisms underlying its inhibitory effects on airway inflammation were further explored in LPS -stimulated Beas-2B cells. ELP was characterized using gas chromatography. The production of inflammatory mediators in bronchoalveolar lavage fluid (BALF) was determined using an enzyme-linked immunosorbent assay. The expression of MUC5AC, MUC5B, and p-p65 in the lung tissue was measured using immunohistochemical staining. The gene expression of inflammatory mediators was determined using qRT-PCR. The expression levels of the target proteins were detected by western blotting. Nuclear localization of p65 was determined using an immunofluorescence assay. Compared to the CB model rats, ELP-treated rats showed reduced airway resistance, inflammation, and goblet cell hyperplasia. In BALF, ELP decreased the levels of inflammatory mediators, including TNF-α, IL-6, MIP-1α, and CCL5. ELP also suppressed LPS -induced elevation of MUC5AC, MUC5B, and p-p65 in the lung tissue. The metabolic pathway changes caused by LPS challenge were improved by ELP treatment. In LPS -exposed Beas-2B cells, ELP treatment inhibited the expression of TNFA , IL6 , CCL5 , MCP1 , and MIP2A and decreased the phospho-levels of toll-like receptor 4 (TLR4) signaling-related proteins, including p-p38, p-JNK, p-ERK, p-TBK1, p-IKKα/β, p-IκB, p-p65, and p-c-Jun. ELP also hindered the nuclear translocation of p65, c-Jun, and IRF3. This study showed that ELP has a potential therapeutic effect in LPS-induced CB rat model, possibly by suppressing TLR4 signaling. These results justify the clinical use of ELP for the treatment of pulmonary inflammatory diseases. [ABSTRACT FROM AUTHOR]

Ambient air pollution increases the risk of respiratory mortality and morbidity, but evidence concerning effects of air pollution on chronic bronchitis (CB) is scarce. This study aimed to evaluate the associations of a set of air pollutants with the burden of CB, and to explore potential modifiers on the associations. In 2020, a total of 6,556,440 adults living in the Northwestern region of China were recruited. The Space-Time Extra-Trees model was employed to assess the annual average concentrations of six air pollutants for the three years (2017-2019) before 2020 , and subsequently allocated to the participants based on the latitude and longitude of their home addresses. We investigated the associations between the levels of various air pollutants and the odds of CB using generalized linear mixed models, and conducted multiple sensitivity analyses and subgroup analyses. The odds of CB displays an approximately linear association with particulate matter with aerodynamic diameter ≤2.5 μm (PM 2.5), particulate matter with aerodynamic diameter ≤10 μm (PM 10), while it shows a non-linear relationship with gaseous pollutants. In the adjusted model, the odds ratios and 95% confidence intervals for CB per 10 μg/m3 increase in PM 2.5 , PM 10 , and sulfur dioxide (SO 2) were 1.297 (1.262–1.332), 1.072 (1.064–1.080), and 2.587 (2.186–3.063), respectively. Furthermore, several additional sensitivity analyses demonstrated the stability of these associations. Subgroup analyses found that the aforementioned associations were greater among participants aged below 50 years old and those who smoked and had no leisure time exercise. Long-term exposure to ambient air pollutants may increase the odds of CB, especially among younger people and those with unhealthy lifestyles. [Display omitted] • Evidence concerning ambient air pollution and chronic bronchitis (CB) is limited. • We examined the association between air pollution and CB in northwestern China. • Exposure to particulate and gaseous pollutants was related to higher odds of CB. • Our findings may help develop individual-and population-level interventions to reduce CB burden. [ABSTRACT FROM AUTHOR]

The extracellular signals that initiate intracellular reactions are dispatched by the mitogen-activated protein kinases (MAPKs), which oversee a multitude of cellular activities. p38, Extracellular signal-regulated kinase (ERK), and c-Jun NH2-terminal kinase (JNK) are members of the vertebrate family of MAPKs, and each MAPK signaling pathway consists of a MAPK kinase (MAP3K), a MAPK kinase (MAP2K), and a MAPK. These signaling pathways orchestrate numerous cellular processes, including cell growth, survival, differentiation, and apoptosis. The emergence of various inflammatory respiratory diseases in humans has been linked to the dysregulation of MAPK signaling pathways. Conditions such as asthma, lung cancer, pulmonary fibrosis, and COPD are among the prevalent respiratory ailments where MAPK plays a pivotal role. Additionally, MAPK is implicated in infectious diseases, including COVID-19, pneumonia, and tuberculosis. COPD, asthma, emphysema, chronic bronchitis, and other inflammatory lung disorders highlight the significance of MAPK as a potential target for therapeutic development. Further studies are needed to delve into the molecular mechanisms by which the MAPK signaling pathway contributes to inflammatory lung disorders, representing an area that demands continued research. [ABSTRACT FROM AUTHOR]

Pyrazinamide (PZA)-resistant Mycobacterium tuberculosis has gradually increased in recent years. Therefore, the discovery of drugs that can enhance the effect of PZA has important value in the treatment of tuberculosis. Cinnamomum cassia Blume (Lauraceae) is popularly used in China and Africa to treat gastritis, chronic bronchitis, diabetes and other diseases. The aims of this study were to isolate molecules with anti-Mtb activity from the extract of twig of C. cassia and evaluate the active molecule alone or in combination with PZA against Mycobacterium tuberculosis in vitro and in vivo. Compound 1 , with anti- Mycobacterium tuberculosis activity (MIC = 10 μg/ml), was isolated from the extract of twig of C. cassia using bioassay-guided approach, and identified as cinnamic aldehyde on the basis of its spectroscopic data. The MICs of compound 1 against E. coli, S. aureus, and M. tuberculosis were 640, 320, and 10 μg/ml, respectively. The compound 1 in combination with PZA showed additive effect (FICI: 0.75). Compound 1 showed no toxicity on the growth of Vero cells at concentration of 120 μg/ml. Its selectivity index (SI) was 12. The in vivo experiment showed that compound 1 and PZA clearly act synergistically against Mycobacterium tuberculosis in the murine model. Scanning electron microscopy showed that M. tuberculosis cells swelled, collapsed and ruptured after treatment with sub-inhibitory concentration of compound 1. This implies that the anti- M. tuberculosis mechanism of compound 1 might be associated with disruption of cell wall. The above results indicate that compound 1 could be used as a drug candidate in new regimens design for TB treatment. [Display omitted] • The crude EtOH extract of Cinnamomum cassia showed antimycobacterial activity. • Cinnamic aldehyde was isolated from Cinnamomum cassia and identified as active compound. • Cinnamic aldehyde could significantly enhanced the activity of PZA against M. tuberculosis. • Cinnamic aldehyde and PZA clearly act synergistically against Mycobacterium tuberculosis in the murine model. • Anti- M. tuberculosis mechanism of cinnamic aldehyde might be associated with disruption of cell wall. [ABSTRACT FROM AUTHOR]

: to report on the use of high-dose-rate (HDR) endobronchial interventional radiotherapy (brachytherapy, EBIRT) for palliation of symptoms in patients with lung cancer. : retrospective review of lung cancer patients treated with HDR-EBIRT at our institution (1995–2017). Treatment results and treatment related toxicity were recorded. Clinical response was subjectively evaluated within 3 months after treatment. Overall survival (OS) was analyzed. : 347 patients were identified. The median age was 69 years and the median follow-up time was 13.4 months. Most patients received external beam radiation therapy during the primary treatment. Within 3 months, 87.7% of the patients had complete or major response of their presenting symptoms. OS was 55.2% at 1 year, 18.3% at 2 years. Patients who had complete or major response had a longer median survival than other patients (13 versus 7 months, p = 0.03). Chronic bronchitis was found in 26.8%, while 7.8% of the patients died due to uncontrollable hemoptysis. : HDR-EBIRT is a safe and effective treatment option for the palliative treatment of lung cancer patients. HDR-EBIRT is most suitable as a re-irradiation technique. Further clinical studies are needed to validate its role. [ABSTRACT FROM AUTHOR]

• This the first study to investigate AZLI in the acute exacerbation setting. • We found AZLI use was associated with positive clinical outcomes. • Neither IV antibiotics nor AZLI consistently reduced P. aeruginosa load. • AZLI appeared to disturb the core lung microbiota less than IV antibiotics. • AZTEC-CF will inform the design of larger trials of inhaled antibiotics in the acute setting The objective of this study was to explore the clinical and microbiological outcomes associated with substituting inhaled aztreonam lysine for an intravenous antibiotic in the treatment of acute pulmonary exacerbations of CF. An open-label randomised crossover pilot trial was conducted at a UK CF centre among 16 adults with CF and P. aeruginosa infection. Median [IQR] age was 29.5 [24.5-32.5], mean ± SD forced expiratory volume in 1 second (FEV1) was 52.4 ± 14.7 % predicted. Over the course of two exacerbations, participants were randomised to sequentially receive 14 days of inhaled aztreonam lysine plus IV colistimethate (AZLI+IV), or dual IV antibiotics (IV+IV). Primary outcome was absolute change in % predicted FEV1. Other outcomes evaluated changes in quality of life, bacterial load and the lung microbiota. The difference between mean change in lung function at day 14 between AZLI+IV and IV+IV was +4.6% (95% CI 2.1-7.2, p =0.002). The minimum clinically important difference of the Cystic Fibrosis Revised Questionnaire (CFQ-R) was achieved more frequently with AZLI+IV (10/12, 83.3%) than IV+IV (7/16, 43.8%), p =0.05. No differences were observed for modulation of serum white cell count, C-reactive protein or sputum bacterial load. Microbiome compositional changes were observed with IV+IV (Bray-Curtis r2=0.14, p=0.02), but not AZLI+IV (r2=0.03, p=0.64). In adults with CF and P. aeruginosa infection experiencing an acute pulmonary exacerbation, AZLI+IV improved lung function and quality of life compared to the current standard treatment. These findings support the need for larger definitive trials of inhaled antibiotics in the acute setting. EudraCT 2016-002832-34 ClinicalTrials.org NCT02894684 [ABSTRACT FROM AUTHOR]

• JFEE and JFEE-D inhibit type I allergic reactions in vivo and in vitro. • JFEE and JFEE-D reduced degranulation of RBL-2H3 cells induced by IgE. • The isolate D is an important part of the antiallergic effect of JFEE. • PI3K/Akt pathway play a critical role in JFEE and JFEE-D. Jing-Fang powder (Schizonepeta tenuifolia Briq. and Saposhnikovia divaricata (Turcz.) Schischk.) was used to treat chronic bronchitis, asthma and chronic urticaria. Based on the preliminary results of screening research on the antiallergic effective parts of Jing-Fang powder, its ethyl acetate extract fractions (JFEE) and isolate D (JFEE-D) showed the best anti-allergic effect. RBL-2H3 cell activation degranulation model and mice passive cutaneous anaphylaxis (PCA) reaction model were used to investigate the effects and mechanisms of JFEE and JFEE-D on IgE-mediated type I allergic reactions. LC–MS was utilized to determine the composition of JFEE and JFEE-D. We found that JFEE and JFEE-D significantly reduced β-HEX, histamine, IL-4, IL-6 levels in cell supernatants, and improved the degree and morphology of cell degranulation. JFEE and JFEE-D significantly inhibited the increase of ear vascular permeability and abnormal increase of serum IgE, TNF-α, IL-6 levels. JFEE and JFEE-D inhibited mRNA expression of PI3K and Akt and down-regulated protein expression of PI3K, Akt, p-Akt, and PLCγ1 in sensitized RBL-2H3 cells. The combined use of JFEE and JFEE-D with pathway inhibitor Wortmannin revealed synergistic down-regulation of PI3K, Akt, and p-Akt protein expression. The combined use of pathway agonist IGF-1, JFEE and JFEE-D down-regulated increase of p-Akt/Akt protein expression. Moreover, JFEE and JFEE-D significantly inhibited protein expression of PI3K, p-Akt and PLCγ1 in PCA model mice. These results show that JFEE and JFEE-D inhibit type I allergic reactions by inhibiting PI3K/Akt signaling pathway. [ABSTRACT FROM AUTHOR]

Gleditsiae sinensis fructus Pills (GF) is a famous classical prescription, that is regularly combined with Jujubae fructus (JF) for the treatment of chronic bronchitis (CB) in the clinic. While the clinical efficacy of this combination prescription is clearly established, the active ingredients and molecular mechanisms remain unclear. To elucidate the mechanisms of action of Gleditsiae sinensis fructus Pills combined with Jujubae fructus (GF&JF) against CB based on network pharmacology and experimental verification. The potential targets of GF&JF involved in therapeutic activity against CB were predicted based on network pharmacology and an "ingredients-targets" network constructed. The Metascape database was used for Module, GO functional and KEGG signaling pathway enrichment analyses of potential targets. Molecular docking was applied to simulate the binding activities of key candidate active ingredients to core targets. For experimental verification, a CB model was established through smoking and nasal cavity drip of lipopolysaccharide. Related inflammatory factors, including TNF-α, TGF-β, IL-6 and IL-8 in serum, and IL-4 IL-8, IFN-γ and IL-10 in bronchoalveolar lavage fluid (BALF), were detected using ELISA. Hematoxylin and eosin (H&E) and Masson staining were performed to observe pathological changes in lung and tracheal tissue. The expression of related proteins and mRNAs in the lung tissue were detected using immunohistochemistry (IHC), quantitative real-time PCR, and western blot. In network pharmacology, 36 common targets of GF&JF for CB were screened and the key targets and main signaling pathways identified. The active ingredients quercetin and stigmasterol in GF&JF had more targets for CB, which displayed good binding activity to IL-6, VEGFA, and EGFR, as established from molecular docking results. In vivo , GF&JF effectively inhibit the inflammatory response in CB mice and improved pathological changes in lung and tracheal tissue. In terms of the key proteins of the AGE-RAGE signaling pathway, GF&JF induced significant down-regulation of IL-6, ICAM-1, VCAM-1, EGFR, CASPASE-3, AGEs and RAGE proteins in lung tissue as well as mRNA expression of IL-6, ICAM-1, VCAM-1, EGFR, AGEs and RAGE. The GF&JF combination exerts a good therapeutic effect in CB model mice, which may be attributed to inhibition of the inflammatory response as well as regulation on the expression of AGE-RAGE signaling pathway. In addition, quercetin and stigmasterol appear to be the main active ingredients of GF&JF in the treatment of CB. [Display omitted] • GF was described in "Jingui Yaolue" by Zhongjing Zhang in the Han Dynasty. • Classical prescription GF&JF was an ancient prescription mainly used for chronic bronchitis. • GF&JF has a better therapeutic effect on CB, which may be related to regulating the expression of AGE-RAGE signaling pathway. [ABSTRACT FROM AUTHOR]

Zhisou Powder (ZP), one of the most common prescriptions in traditional Chinese medicine, has been widely used in the treatment of acute or chronic bronchitis and chronic cough. The ZP was composed of Ziwan (Aster tataricus L. f.), Jiegeng (Platycodon grandiflorus (Jacq.) A. DC.), Jingjie (Nepeta cataria L.), Baibu (Stemona sessilifolia (Miq.) Miq.), Baiqian (Vincetoxicum glaucescens (Decne.) C. Y. Wu & D. Z. Li), Chenpi (Citrus × aurantium f. deliciosa (Ten.) M. Hiroe) and Gancao (Glycyrrhiza uralensis Fisch. ex DC.), with plant names among it checked with MPNS (http://mpns.kew.org). But until now, the key active components and targets of ZP, and related mechanism of ZP in the treatment of chronic bronchitis (CB) remain unclear. This study combined UPLC-Q-Exactive-Orbitrap-MS, network pharmacology, metabonomics with experiment verification to explore potential mechanism of ZP in the treatment of CB. UPLC-Q-Exactive-Orbitrap-MS was performed to analyze the chemical components of ZP. The potentially effective components, attractive targets and critical signaling pathways of Zhisou Powder in the treatment of CB were screened by UPLC-Q-Exactive-Orbitrap-MS combined with network pharmacology. Additionally, the CB model rats induced by SO 2 were used to evaluate the anti-chronic bronchitis activity of ZP in vivo. The pulmonary pathology was determined by hematoxylin-eosin staining. Meanwhile, PI3K/Akt/HIF-1α/VEGFA signaling pathway predicted from network pharmacology was verified by Western blot and RT-PCR. Lastly, the metabolic changes of arachidonic acid (AA) in ZP-treated rats were quantitatively analyzed by LC-MS targeted metabonomics, and the proteins expression involved in AA metabolic pathway were detected by immunohistochemistry, immunofluorescence and Western blot. The main active components of ZP in the treatment of CB selected by network pharmacology and UPLC-Q-Exactive-Orbitrap-MS technology were quercetin, kaempferol, luteolin, galangin, isorhamnetin, naringenin, nobiletin, formononetin and so on. The core targets of these components were predicted to be TP53, TNF, IL-6, VEGFA, CASP3, IL-1β, JUN, PTGS2. Enrichment of KEGG pathway analysis found that PI3K/Akt/HIF-1α/VEGFA signaling pathway might play a key role in the treatment of CB with ZP. The in vivo study showed that ZP significantly improved the pathological changes of SO 2 -treated lung tissue and inhibited the activation of PI3K/Akt/HIF-1α/VEGFA signaling pathway. The changes of AA and its metabolites in vivo were studied by targeted metabonomics, and it showed that ZP could reprogram the disorder of AA metabolism which contributed to the treatment of CB with ZP. ZP displayed good therapeutic effect on CB model rats through inhibiting PI3K/Akt/HIF-1α/VEGFA signaling pathway to exhibit anti-inflammatory effect and reprogramming disordered metabolic pathway of arachidonic acid. [Display omitted] [ABSTRACT FROM AUTHOR]

• Cough is a defense mechanism for clearing the airways but may become troublesome. • Chronic cough of known and unknown cause(s) frequently requires medical attention. • Chronic cough of known cause(s) must be treated according to guidelines. • Chronic refractory cough may benefit from neuromodulatory/speech pathology therapy. • Novel promising neuromodulatory agents are in clinical development. Cough, a defense mechanism for clearing the airways of secretions, exudate, or foreign bodies, may become a troublesome symptom. Chronic cough, one of the most frequent symptoms requiring medical attention, is often not due to identifiable causes in adults. Chronic productive cough defines chronic bronchitis, and thus is present in 100% of these patients, and frequently in patients with bronchiectasis, cystic fibrosis, and chronic infectious respiratory diseases. However, chronic cough is most frequently dry. Thus, chronic cough in adults is a difficult syndrome requiring multidisciplinary approaches, particularly to diagnose and treat the most frequent identifiable causes, but also to decide which patients may benefit by treating the central cough hypersensitivity by neuromodulatory therapy and/or non-pharmacologic treatment (speech pathology therapy). Recent guidelines provide algorithms for diagnosis and assessment of cough severity; particularly chronic cough in adults. After excluding life-threatening diseases, chronic cough due to identifiable causes (triggers and/or diseases), particularly smoking and/or the most frequent diseases (asthma, chronic bronchitis, chronic obstructive pulmonary disease, eosinophilic bronchitis, and adverse reactions to drugs [angiotensin-converting enzyme inhibitors and sitagliptin]) should be treated by avoiding triggers and/or according to guidelines for each underlying disease. In patients with troublesome chronic cough due to unknown causes or persisting even after adequate avoidance of triggers, and/or treatment of the underlying disease(s), a symptomatic approach with neuromodulators and/or speech pathology therapy should be considered. Additional novel promising neuromodulatory agents in clinical development (e.g., P2X3 inhibitors) will hopefully become available in the near future. [ABSTRACT FROM AUTHOR]

Emphysema is one of three main lung pathologies in Chronic Obstructive Pulmonary Disease, along with chronic bronchitis and small airway obstruction. The diagnosis is based on detection of low attenuation areas in lung tissue on chest Computed Tomography, either visual by a radiologist, or automatic by the applied Computed Tomography software. Results of the studies on the association between emphysema and lung cancer incidence are mixed. Many studies have demonstrated, that chronic lung diseases, like Chronic Obstructive Pulmonary Disease, are associated with lung cancer morbidity. There is also evidence, that emphysema can be related with worse prognosis in patients with detected lung cancer. In this review article we aim to summarize current knowledge about emphysema detection and evaluation on Computed Tomography, both quantitative and qualitative. We also summarize current data on correlation between emphysema and lung cancer, as well as its potential use in selecting patients, who would most benefit from lung cancer screening. • There are several methods of lung emphysema evaluation, both qualitative and quantitative. • Visual assessment of emphysema on CT image is superior to automatic estimation in terms of prediction of lung cancer risk. • In patients with detected lung cancer, presence of emphysema is related with worse prognosis. [ABSTRACT FROM AUTHOR]

• Postural abnormalities are more common in people with emphysema. • People with emphysema have more head protraction and greater scapular elevation. • Postural differences exist between COPD patients and healthy individuals. Few studies have demonstrated postural abnormalities in patients with chronic obstructive pulmonary disease - when compared with healthy individuals. However, none of these studies have compared postural abnormalities in different phenotypes of chronic obstructive pulmonary disease. To compare the thoracic posture between two phenotypes of chronic obstructive pulmonary disease (emphysema and chronic bronchitis) with healthy individuals. Forty individuals with chronic obstructive pulmonary disease (20 with chronic bronchitis, 67 ± 3.5 years, 20 with emphysema, 67.7 ± 4 years) and 20 age-matched healthy individuals (67.3 ± 3.9 years) underwent postural assessment which was performed using photogrammetric measurements of head protraction, shoulder protraction, thoracic kyphosis angle, coronal shoulder angle, and scapular elevation. Significant differences were found amongst the groups in protraction of head (emphysema vs. chronic bronchitis, mean difference = 7.63°, 95% confidence interval [CI] = 2.10, 13.15°; emphysema vs. healthy, 7.91°, 95% CI = 2.38, 13.43°), protraction of shoulder (emphysema vs. healthy, 13.69°, 95% CI = 6.96, 20.43°; chronic bronchitis vs. healthy, 8.11°, 95% CI = 1.38, 14.85°), thoracic kyphosis (emphysema vs. healthy, −11.59°, 95% CI = −17.26, −5.92°; chronic bronchitis vs. healthy, −6.75°, 95% CI = −12.41, −1.08°), coronal shoulder angle (emphysema vs. chronic bronchitis, 1.01°, 95% CI =.22, 1.80°; emphysema vs. healthy, 1.59°, 95% CI =.80, 2.38°) and scapular elevation (emphysema vs. chronic bronchitis, =.74 cm, 95% CI =.34, 1.15 cm; emphysema vs. healthy,.99 cm, 95% CI =.59, 1.40 cm). People with emphysema show greater degree of postural malalignments in terms of head and shoulder protraction, thoracic kyphosis, symmetry of shoulders and scapular elevation than patients with chronic bronchitis and age-matched healthy individuals. These observations emphasize the importance of postural assessment in individuals with chronic obstructive pulmonary disease, particularly if they are emphysematous. [ABSTRACT FROM AUTHOR]

• The influenza vaccination rate was 2.4% from a national cross-sectional study. • The rate was 3.8% for people ≥60 years and 4.0% for chronically ill people. • The rate was 3.6% for COPD patients and 4.8% for chronic bronchitis patients. • Widespread reimbursement vaccination policy for the old is needed. • Strategies towards patients with chronic diseases need urgent attention. Influenza vaccination is the most effective way to prevent influenza. Few studies on its rate were reported throughout China and for populations with chronic diseases. An estimation of the rates in China was accomplished. All data were from a national cross-sectional survey of a sample representing the population aged 40 years or older in mainland China in 2014–15. A total of 74,484 individuals with complete self-reported influenza vaccination status were analyzed in 2018–19. The overall influenza vaccination rate was 2.4% (95% CI 1.4–3.3) with 1.7% (95% CI 1.2–2.2) for the age group 40–59 years and 3.8% (95% CI 1.6–5.9) for the group ≥60 years. The rate was 4.0% (95% CI 2.0–5.9) among people with a chronic disease. People with asthma and people with emphysema had the highest rates (7.1%, 95% CI 3.2–11.0 and 6.6%, 95% CI 3.6–9.7) while people with chronic obstructive pulmonary disease (COPD) and people with chronic bronchitis had the lower rates (3.6%, 95% CI 2.0–5.2 and 4.8%, 95% CI 2.6–7.0). The rate was the highest among former smokers (3.3%, 95% CI 2.3–4.4) compared to current smokers (1.8%, 95% CI 0.9–2.7) and never smokers (2.5%, 95% CI 1.4–3.6). People living with finance-reimbursed vaccination policy, a positive factor for vaccination, had a higher vaccination rate (11.5%, 95% CI 10.8–12.2) (p < 0.05). People with older age, higher education level, occupation of professionals or technical personnel, living in rural areas or Northern China, former/never smoking were more likely to be vaccinated (p < 0.05). The influenza vaccination rate is low among adults aged ≥40 years, those ≥60 years and those with chronic diseases in China. Reimbursement policy targeting the elderly should be implemented widely and strategies towards patients with chronic diseases need urgent attention to increase the influenza vaccination coverage. [ABSTRACT FROM AUTHOR]

Introduction: The association between e-cigarette use and chronic bronchitis, emphysema, and chronic obstructive pulmonary disease has not been studied thoroughly, particularly in populations defined by concomitant combustible smoking status.Methods: Using pooled 2016 and 2017 data from the Behavioral Risk Factor Surveillance System, investigators studied 705,159 participants with complete self-reported information on e-cigarette use, combustible cigarette use, key covariates, and chronic bronchitis, emphysema, or chronic obstructive pulmonary disease. Current e-cigarette use was the main exposure, with current use further classified as daily or occasional use. The main outcome was defined as reported ever having a diagnosis of chronic bronchitis, emphysema, or chronic obstructive pulmonary disease. For all the analyses, multivariable adjusted logistic regression was used, with the study population stratified by combustible cigarette use status (never, former, or current). All the analyses were conducted in 2019.Results: Of 705,159 participants, 25,175 (3.6%) were current e-cigarette users, 64,792 (9.2%) current combustible cigarette smokers, 207,905 (29.5%) former combustible cigarette smokers, 432,462 (61.3%) never combustible cigarette smokers, and 14,036 (2.0%) dual users of e-cigarettes and combustible cigarettes. A total of 53,702 (7.6%) participants self-reported chronic bronchitis, emphysema, or chronic obstructive pulmonary disease. Among never combustible cigarette smokers, current e-cigarette use was associated with 75% higher odds of chronic bronchitis, emphysema, or chronic obstructive pulmonary disease compared with never e-cigarette users (OR=1.75, 95% CI=1.25, 2.45), with daily users of e-cigarettes having the highest odds (OR=2.64, 95% CI=1.43, 4.89). Similar associations between e-cigarette use and chronic bronchitis, emphysema, or chronic obstructive pulmonary disease were noted among both former and current combustible cigarette smokers.Conclusions: The results suggest possible e-cigarette-related pulmonary toxicity across all the categories of combustible cigarette smoking status, including those who had never smoked combustible cigarettes. [ABSTRACT FROM AUTHOR]

Introduction: The critical sociodemographic, lifestyle and diseases factors influencing sarcopenia, defined by the current European Working Group on Sarcopenia 2 (EWGSOP2) classification and cut-off points, have not yet been fully elucidated. This study aimed, therefore, to determine sociodemographic, anthropometric, lifestyle and health-related factors associated with sarcopenia using the new EWGSOP2 definition.Study Design: 396,283 participants (52.8 % women, age 38-73 years) were included in this cross-sectional study. The potential factors associated with sarcopenia were allocated to four categories: sociodemographic (sex, age, education, income and professional qualification), anthropometric (nutritional status, abdominal obesity, body fat and birth weight), lifestyle (physical activity, smoking, sleeping, sitting time, TV viewing, alcohol, and dietary intakes) and health status (self-reported prevalent diseases). P-values were corrected for multiple testing using the Bonferroni method.Results: Age, women, lower education, higher deprivation, underweight, lower birth weight, and chronic diseases such as rheumatoid arthritis, chronic bronchitis and osteoporosis were associated with a higher likelihood of sarcopenia. Conversely, overweight, obesity, as well as a self-reported higher intake of energy, protein, vitamins (B12 and B9) and minerals (potassium, calcium and magnesium) were associated with lower odds of sarcopenia.Conclusion: Women, people aged over 65 years, underweight people and those with rheumatoid arthritis were most likely to have sarcopenia. Considering the increase in the ageing population, sarcopenia is likely to become more prevalent. Identifying factors associated with sarcopenia could inform future strategies for early identification of individuals at high risk of sarcopenia and therefore the implementation of preventive strategies against the disease. [ABSTRACT FROM AUTHOR]

• Patients with COPD commonly have comorbid conditions, including sleep disorders. • Most frequent sleep disorders in COPD include sleep disordered breathing, insomnia and restless legs. • The coexistence of sleep disorders and COPD impacts a range of clinical outcomes. • Sleep disorders should be actively diagnosed and treated in patients with COPD. A good night's sleep is a prerequisite for sustainable mental and physical health. Sleep disorders, including sleep disordered breathing, insomnia and sleep related motor dysfunction (e.g., restless legs syndrome), are common in patients with chronic obstructive pulmonary disease (COPD), especially in more severe disease. COPD is commonly associated with multimorbidity, and sleep disorders as a component of this multimorbidity spectrum have a further negative impact on COPD-related comorbidities. Indeed, concomitant diseases in COPD and in obstructive sleep apnea (OSA) are similar, suggesting that the combination of COPD and OSA, the so called OSA-COPD overlap syndrome (OVS), affects patient outcomes. Potential clinically important interactions of OVS exist in cardiovascular and metabolic disease, arthritis, anxiety, depression, neurocognitive disorder and the fatigue syndrome. Correct diagnosis for recognition and treatment of sleep-related disorders in COPD is recommended. However, surprisingly limited information is available and further research and improved diagnostic tools are needed. In the absence of clear evidence, we agree with the recommendation of the Global Initiative on Chronic Obstructive Lung Disease that sleep disorders should be actively searched for and treated in patients with COPD. We believe that both aspects are important components of the holistic approach required in patients with chronic multimorbid conditions. [ABSTRACT FROM AUTHOR]

• Serum HE4 was elevated in patients with pulmonary tuberculosis. • Serum HE4 associated with the severity of disease. • Serum HE4 could be a clinical biomarker for patients with pulmonary tuberculosis. Human epididymis protein 4 (HE4) has been recognized as a biomarker which elevated in various diseases. The aim of this study was to evaluate the value of serum HE4 in pulmonary tuberculosis (PTB). Serum HE4 concentrations were determined in 127 PTB, 88 chronic bronchitis (CHB), and 105 healthy control subjects by chemiluminescent microparticle immunoassay. Receiver operating characteristic (ROC) curves and Spearman's correlation analysis were performed for investigating value of HE4. Serum HE4 concentrations were significantly increased in PTB (62.8 pmol/L, IQR 45.8–90.7), compared with that of CHB (50.2 pmol/L, IQR 42.3–64.3, P = 0.0002) and normal control (35.4 pmol/L, IQR 31.1–42.9, P < 0.0001). ROC curve suggested that the AUC of HE4 used to discriminate PTB from CHB was 0.647 (95% CI, 0.574–0.719), with the cutoff value, sensitivity, specificity, PPV, and NPV at 71.9 pmol/L, 0.417, 0.852, 0.672 and 0.543, respectively. Meanwhile, compared with mild to moderated PTB, the levels of HE4 in advanced PTB were significantly elevated (75.8 vs. 57.7 pmol/L, P = 0.0052). What's more, the levels of HE4 in PTB were found to be significantly associated with the albumin, CRP, and cavity (r = −0.2996, P = 0.0006, r = 0.265, P = 0.0026, r = 0.4699, P < 0.0001, respectively). Elevated serum HE4 concentration could be used as a biomarker for the diagnosis and assessment of disease severity in PTB. [ABSTRACT FROM AUTHOR]

Introduction: E-cigarettes deliver an aerosol of nicotine by heating a liquid and are promoted as an alternative to combustible tobacco. This study determines the longitudinal associations between e-cigarette use and respiratory disease controlling for combustible tobacco use.Methods: This was a longitudinal analysis of the adult Population Assessment of Tobacco and Health Waves 1, 2, and 3. Multivariable logistic regression was performed to determine the associations between e-cigarette use and respiratory disease, controlling for combustible tobacco smoking, demographic, and clinical variables. Data were collected in 2013-2016 and analyzed in 2018-2019.Results: Among people who did not report respiratory disease (chronic obstructive pulmonary disease, chronic bronchitis, emphysema, or asthma) at Wave 1, the longitudinal analysis revealed statistically significant associations between former e-cigarette use (AOR=1.31, 95% CI=1.07, 1.60) and current e-cigarette use (AOR=1.29, 95% CI=1.03, 1.61) at Wave 1 and having incident respiratory disease at Waves 2 or 3, controlling for combustible tobacco smoking, demographic, and clinical variables. Current combustible tobacco smoking (AOR=2.56, 95% CI=1.92, 3.41) was also significantly associated with having respiratory disease at Waves 2 or 3. Odds of developing respiratory disease for a current dual user (e-cigarette and all combustible tobacco) were 3.30 compared with a never smoker who never used e-cigarettes. Analysis controlling for cigarette smoking alone yielded similar results.Conclusions: Use of e-cigarettes is an independent risk factor for respiratory disease in addition to combustible tobacco smoking. Dual use, the most common use pattern, is riskier than using either product alone. [ABSTRACT FROM AUTHOR]

• The role of autoantibodies in chronic obstructive pulmonary disease (COPD) has been extensively researched in recent years. • The strongest associations are with autoantibodies to endothelium/epithelium, IgG, cytokeratin, nuclei and collagen. • The relationship between autoantibody levels and disease phenotype and disease severity require further research. Chronic Obstructive Pulmonary Disease (COPD) is a major cause of death worldwide in which the involvement of autoimmunity has been widely investigated and debated. The role of autoantibodies in COPD has been extensively researched in recent years. The aim of this systematic review is to assess the association between autoantibodies and COPD and analyse whether autoantibody levels correlate with disease severity and/or phenotype. PubMed, Embase, OpenGrey and the reference lists of articles were searched. The strongest evidence for an association between autoantibodies and COPD lies with anti-endothelial/epithelial cell autoantibodies (7 studies, all positive), rheumatoid factor autoantibodies (4 studies, all positive), anti-cytokeratin autoantibodies (3 studies, all positive), anti-nuclear autoantibodies (8 studies, 7 positive) and anti-collagen autoantibodies (10 studies, 6 positive). This review also identifies several other autoantibodies which had both positive and negative associations with COPD, however the evidence for these was not as strong and/or the number of studies is low, and further research is required. In particular, a clear case can be made for the potential importance of autoantibodies to carbonylated proteins. The relationship between autoantibody levels and disease severity requires further research with only 17/43 studies investigating this; however, 12 of the studies did show a positive association, making it a promising area for future research. There was also not enough evidence available on the relationship between autoantibody levels and disease phenotype to draw any conclusions, with only 2 studies investigating it (1 positive and 1 negative). This review has shown very promising evidence for the association of several autoantibodies in COPD and has identified those autoantibodies which require further research. [ABSTRACT FROM AUTHOR]

This meta-analysis study was performed to examine the relationship between occupational exposure to pesticides and the risk of obstructive pulmonary diseases such as chronic obstructive pulmonary disease (COPD) and chronic bronchitis. This is a systematic review and meta-analysis study. PubMed and Scopus databases were searched for English-language publications. Eight cohort studies and one case–control study were included in the pooled analysis. These studies had a total of 101,353 participants from eleven different countries and were published between 2006 and 2018. The heterogeneity among the studies was high (P < 0.001, I2 = 68.7%). In a random-effects model meta-analysis, a pooled odds ratio (OR) analysis showed that there was a direct relationship between occupational exposure to the pesticides and obstructive pulmonary diseases (OR = 1.33, 95% confidence interval [CI]: 1.21–1.47). A positive significant relationship was also observed between exposure to the pesticides and risk of chronic bronchitis (OR = 1.27, 95% CI: 1.23–1.31). Also, there was a significant relationship between occupational exposure to the pesticides and an increased risk of COPD (OR = 1.44, 95% CI: 1.14–1.81). No evidence of publication bias was found among the studies according to the results of the Egger's test (P of bias = 0.157). Findings of this study show that occupational exposure to pesticides can be associated with an increased risk of obstructive lung diseases including chronic bronchitis and COPD. • An association between the type of pesticide and risk of obstructive lung diseases was shown. • A significant positive risk of chronic bronchitis and occupational exposure to pesticides was observed. • A significant positive risk of chronic obstructive pulmonary disease (COPD) and occupational exposure to pesticides was shown. • COPD diagnosis by GOLD and LLN criteria showed a significant association with occupational exposure to pesticides. [ABSTRACT FROM AUTHOR]

Chronic bronchitis refers to a chronic condition that is characterized by long-term inflammation of the bronchi. It is of great importance to understand the contributing risk factors for chronic bronchitis because it is associated with adverse outcomes such as healthcare burden and mortality. We aimed to understand if the personality traits could predict ever and the 7-year risk of clinically diagnosed chronic bronchitis in a large cohort of participants from the UK. We analyzed data from Understanding Society: the UK Household Longitudinal Study, which consists of 15,387 middle-aged or older participants for the cross-sectional analysis and 8783 middle-aged or older adults for the longitudinal analysis using two binary logistic regressions. We found that Neuroticism (OR = 1.36, p < 0.001, 95% C.I. [1.23, 1.51]), Conscientiousness (OR = 0.87, p = 0.014, 95% C.I. [0.78, 0.97]), and Extraversion (OR = 1.15, p = 0.009, 95% C.I. [1.04, 1.29]) are related to a higher chance of ever clinically diagnosed chronic bronchitis. However, Agreeableness and Openness were not related to the chance of ever clinically diagnosed chronic bronchitis. Moreover, Conscientiousness (OR = 0.72, p = 0.012, 95% C.I. [0.55, 0.93]) was related to a lower risk of future clinical diagnosis of chronic bronchitis whereas Extraversion (OR = 1.35, p = 0.024, 95% C.I. [1.04, 1.76]) was associated with a higher risk of future chronic bronchitis. However, Neuroticism, Agreeableness, and Openness were not related to change of ever clinically diagnosed chronic bronchitis. We showed that personality can identify people who are at greater risk of chronic bronchitis, which has translational utility for healthcare of middle-aged and older adults. • Neuroticism is positively associated with ever chronic bronchitis. • Conscientiousness is negatively related to ever and future chronic bronchitis. • Extraversion is positively associated with ever and future chronic bronchitis. [ABSTRACT FROM AUTHOR]

Occupational exposure to animal production is associated with chronic bronchitis symptoms; however, few studies consider associations with chronic obstructive pulmonary disease (COPD). We estimated associations between animal production activities and prevalence of self-reported COPD among farmers in the Agricultural Health Study. During a 2005–2010 interview, farmers self-reported information about: their operations (i.e., size, type, number of animals, insecticide use), respiratory symptoms, and COPD diagnoses (i.e., COPD, chronic bronchitis, emphysema). Operations were classified as small or medium/large based on regulatory definitions. Farmers were classified as having a COPD diagnosis, chronic bronchitis symptoms (cough and phlegm for ≥3 months during 2 consecutive years), or both. Polytomous logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Of 22,491 participating farmers (median age: 59 years), 922 (4%) reported a COPD diagnosis only, 254 (1%) reported a diagnosis and symptoms, and 962 (4%) reported symptoms only. Compared to raising no commercial animals, raising animals on a medium/large operation was positively associated with chronic bronchitis symptoms with (OR: 1.59; 95% CI: 1.16, 2.18) and without a diagnosis (OR: 1.69; 95% CI: 1.42, 2.01). Ever use of multiple organophosphates, carbaryl, lindane, and permethrin were positively associated with chronic bronchitis symptoms. Animal production work, including insecticide use, was positively associated with chronic bronchitis symptoms; but not consistently with COPD diagnosis alone. Our results support the need for further investigation into the role of animal production-related exposures in the etiology of COPD and better respiratory protection for agricultural workers. • Although smoking is the most important risk factor for COPD, 15–20% of COPD in the United States may be related to occupational exposures, with this proportion being 30–48% of COPD among non-smokers. • Few studies have examined the association between animal production work and manifestations of COPD. • Farmers who raised animals on a medium or large operation had higher odds of self-reported chronic bronchitis symptoms with and without a COPD diagnosis compared with farmers raising no animals. • Ever use of specific insecticides was positively associated with self-reported chronic bronchitis symptoms. [ABSTRACT FROM AUTHOR]

Abstract Ethnopharmacological relevance Srolo Bzhtang (SBT), a traditional Tibetan medicine formula, was composed of three herbs, Solms-Laubachia eurycarpa , Bergenia purpurascens , Glycyrrhiza uralensis , and one lac, and was first documented in the ancient Tibetan medical work Four Medical Tantras (rGyud-bzhi) in the eighth century AD. It has been widely used to treat lung "phlegm-heat" syndromes such as chronic bronchitis and chronic obstructive pulmonary disease (COPD). Objective The aim of this study was to evaluate the potential influences of aqueous extract of SBT on airway inflammation and mucus secretion and to reveal the underlying mechanism in a rat model of cigarette smoke (CS)-induced chronic bronchitis (CB). Materials and methods Sixty male Sprague-Dawley rats were randomly divided to six groups: control (room air exposure), model (CS exposure), DEX (CS exposure and 0.2 mg/kg/day dexamethasone), and three SBT (CS exposure and 1.67, 2.50, and 3.34 g/kg/day SBT) groups. DEX and the three doses of SBT were administered by oral gavage every day for eight weeks. Pathological changes and mucus expression in the lung tissue were determined by hematoxylin and eosin (H&E), Alcian blue-periodic acid-Schiff (AB-PAS) and immunohistochemical staining. The levels of cytokines in bronchoalveolar lavage fluid (BALF) were assessed by ELISA. Western blot analysis and qRT-PCR were performed to explore the effects of SBT on the expression of IL-13, STAT6 and MUC5AC. Results Pretreatment with SBT attenuated the TNF-α, IL-8, IL-13 expression levels in BALF and the inflammatory cell infiltration in bronchial walls and peribronchial lung tissue. SBT exhibited a dose-dependent downregulation of MUC5AC expression as assessed by AB-PAS and immunohistochemical staining. The protein and mRNA levels of IL-13, STAT6/p-STAT6 and MUC5AC were also downregulated by SBT preconditioning. Conclusion These results for the first time demonstrated that SBT exhibited protective effects on CS-induced airway inflammation and MUC5AC hypersecretion, which might be related to the downregulation of the IL-13/STAT6 signaling pathway. Graphical abstract fx1 [ABSTRACT FROM AUTHOR]

Abstract With increasing air pollution, chronic bronchitis (CB) has become a major public health problem worldwide. Previous studies have shown beneficial effects of Bergenin (Ber) on chronic bronchitis. To facilitate understanding of the pathogenesis underlying CB as well as to elucidate the Ber therapeutic mechanism, it is crucial to confirm the rational biomarkers of CB and its treatment. This study aimed to investigate the preventive chronic bronchitis mechanism of Ber by applying a serum metabolomics strategy. In this study, 18 Sprague-Dawley rats were randomly divided into three groups,with six rats in each group. Rats from the CB and Ber groups were exposed to tobacco smoke for 1 hd−1 (1 h per day) for 28 days. Ber was administered orally to Ber rats 3 h after exposure every day, and the others were administered water. According to the morphometric analysis of the airway epithelium and the count of white blood cells in the bronchoalveolar lavage fluid, Ber suppressed the infiltration of inflammatory cells, inhibited the secretion of mucus, and reduced white blood cells in bronchoalveolar lavage fluid. The metabolic profiles of sera were analyzed by multivariate statistical analyses, including PCA, PLS-DA and OPLS-DA models, and revealed that the levels of thirteen metabolites were significantly changed and identified as potential biomarkers in the CB group and Ber group. The results suggested that the therapeutic mechanism of Ber may be related to the regulation of dysfunctions in glycerophospholipid, tryptophan, arginine and proline metabolism induced by CB, and changes in arachidonic acid metabolism. [ABSTRACT FROM AUTHOR]

Highlights • CM is associated with an increased risk of psychopathological symptoms. • CM is associated with an increased risk of diabetes mellitus, hypothyroidism, and chronic bronchitis/emphysema/COPD in adulthood. • Psychopathological symptoms drive some proportion of the association between child maltreatment and physical health. • The association between child maltreatment and physical health is not driven entirely by psychopathological symptoms. Abstract Background The aim of this study was to assess the associations between child maltreatment (CM), psychopathological symptoms, and onset of diabetes mellitus, hypothyroidism (i.e., low metabolism), and chronic bronchitis/emphysema/COPD in adulthood. Methods The present analysis used cross-sectional data collected in 2007–2008 within the Tromsø Study, Norway (N = 12,981). CM was measured with a single item, and self-reported information on psychopathological symptoms and physical health outcomes was used. The associations between CM, psychopathological symptoms, and physical health outcomes were assessed with linear and Poisson regression models. Mediation was assessed with difference-in-coefficients method. Results In the fully-adjusted models, CM was associated with higher levels of anxiety and depression, psychological distress, difficulty in sleeping, insomnia, and use of sleeping pills and antidepressants in adulthood (p < 0.05). Moreover, CM was associated with a more than two-folds increased risk of consultation with psychiatrist (p < 0.001), a 26% increased risk of forgetfulness (p < 0.001), a 15% increased risk of decline in memory (p < 0.001), and a 96% increased risk of psychiatric problems (p < 0.001) over the course of life. In the fully-adjusted models, CM was associated with a 27–82% increased risk of physical health outcomes in adulthood (p < 0.05). Indicators of psychopathological symptoms significantly (p < 0.05) mediate the associations between CM and physical health outcomes. Limitations The design of this study is cross-sectional, and all measures are self-reported. Conclusion The associations between retrospectively-reported CM and physical health outcomes in adulthood are partially driven by psychopathological symptoms in adulthood. [ABSTRACT FROM AUTHOR]

Abstract China is in a critical stage of ambient air quality management after global attention on pollution in its cities. Industrial development and urbanization have led to alarming levels of air pollution with serious health hazards in densely populated cities. The quantification of cause-specific PM 2.5 -related health impacts and corresponding economic loss estimation is crucial for control policies on ambient PM 2.5 levels. Based on ground-level direct measurements of PM 2.5 concentrations in 338 Chinese cities for the year 2016, this study estimates cause-specific mortality using integrated exposure-response (IER) model, non-linear power law (NLP) model and log-linear (LL) model followed by morbidity assessment using log-linear model. The willingness to pay (WTP) and cost of illness (COI) methods have been used for PM 2.5 -attributed economic loss assessment. In 2016 in China, the annual PM 2.5 concentration ranged between 10 and 157 μg/m3 and 78.79% of the total population was exposed to >35 μg/m3 PM 2.5 concentration. Subsequently, the national PM 2.5 -attributable mortality was 0.964 (95% CI: 0.447, 1.355) million (LL: 1.258 million and NPL: 0.770 million), about 9.98% of total reported deaths in China. Additionally, the total respiratory disease and cardiovascular disease-specific hospital admission morbidity were 0.605 million and 0.364 million. Estimated chronic bronchitis, asthma and emergency hospital admission morbidity were 0.986, 1.0 and 0.117 million respectively. Simultaneously, the PM 2.5 exposure caused the economic loss of 101.39 billion US$, which is 0.91% of the national GDP in 2016. This study, for the first time, highlights the discrepancies associated with the three commonly used methodologies applied for cause-specific mortality assessment. Mortality and morbidity results of this study would provide a measurable assessment of 338 cities to the provincial and national policymakers of China for intensifying their efforts on air quality improvement. Graphical abstract The spatial distributions of annual mean PM 2.5 concentrations (μg/m3) (left) and corresponding total premature mortality per 100,000 population attributable to PM 2.5 (right) in 338 cities in China. Unlabelled Image Highlights • This study provides a comprehensive analysis of PM 2.5 associated health risk in China using three most prevalent methods. • Total PM 2.5 -related death was 0.964 million using IER method, 1.258 million using LL and 0.770 million using NPL method. • Cities with high premature mortality were largely located in heavily polluted and densely populated regions. • Total economic loss due to PM 2.5 exposure was 101.39 billion US$, about 0.91% of the total Chinese GDP. • Only 8.3% of total premature deaths could be avoided by meeting national PM 2.5 -target in 2030. [ABSTRACT FROM AUTHOR]

Several researchers have raised the concern that the cross-sectional association of retrospectively reported childhood adversity with self-reported onset of asthma and chronic bronchitis in adulthood may be confounded, as well as mediated by an individual's mental health. The aim of this study was to assess the effect of retrospectively reported childhood adversity on self-reported onset of asthma and chronic bronchitis in adulthood, independent of potential confounding and mediating variables (including respondent's mental health). We used data collected in 2007-2008 within the framework of the Tromsø Study (N = 12,981), a representative study of adult men and women in Norway. The associations of childhood adversity with asthma and chronic bronchitis were assessed with Poisson regression models. Relative risks (RR) and 95% confidence intervals (CI) were estimated with bias-corrected bootstrapping. Childhood adversity was associated with a 9% increased risk of asthma (RR = 1.09, 95% CI: 1.02, 1.16) and a 14% increased risk chronic bronchitis (RR = 1.14, 95% CI: 1.03, 1.26) in adulthood, independent of age, sex, parental history of psychiatric problems/asthma/dementia, education, smoking, social support, and respondent's mental health. Controlling for indicators of respondent's mental health reduced the strength of associations of childhood adversity with asthma and chronic bronchitis; however, the associations were still present in the same direction (p < .05). These findings suggest that the association of retrospectively reported childhood adversity with asthma and chronic bronchitis is independent of respondent's mental health. We recommend controlling for indicators of the respondent's mental health to assess an unbiased association of retrospectively measured childhood adversity with self-reported asthma and chronic bronchitis. [ABSTRACT FROM AUTHOR]

We aim to: 1) investigate whether starting cardiac rehabilitation (CR) during the COVID-19 period was influential on new-onset depressive symptoms, 2) examine the relationship between sociodemographic and medical factors with the new-onset of depressive symptoms before and during the COVID-19 period in UK patients commencing CR. The national audit of cardiac rehabilitation (NACR) data were used and the two years of data before COVID-19 and during COVID-19 were analysed (Feb,2018 – Nov,2021). Hospital Anxiety and Depression Scale measurement was used to assess depressive symptoms. Bivariate analysis and logistic regression were conducted to examine the influence of the COVID-19 period on new-onset depressive symptoms and the patient characteristics associated with it. 71055 patients screened for new-onset depressive symptoms were included in the analysis. Based on multivariate analysis, patients commencing CR during COVID-19 were 8% more likely to have new onset depressive symptoms compared to patients commencing before COVID-19. Smoking (OR: 1.26, 95%CI: 1.11, 1.43), physical inactivity (OR: 1.86, 95%CI: 1.74, 1.98), high anxiety (OR: 1.45, 95%CI: 1.44, 1.46), being male (OR: 1.21, 95%CI: 1.12, 1.30), single (OR: 1.25, 95%CI: 1.16, 1.35), having comorbidities of arthritis, diabetes, chronic bronchitis, emphysema, claudication (OR range: 1.19 to 1.60), receiving CABG treatment (OR: 1.47, 95%CI: 1.25, 1.73), and having heart failure (OR: 1.33, 95%CI: 1.19, 1.48) were the factors associated with having new-onset depressive symptoms at the start of CR. Our findings have shown that starting CR during the COVID-19 period was associated with increased odds of having new-onset depressive symptoms. • 71,055 patients screened for new onset depression during cardiac rehabilitation (CR). • Attending CR during the COVID-19 pandemic was associated with new onset depression. • Having heart failure was associated with new onset depression. • Receiving CABG treatment was associated with new onset depression. • Several comorbid conditions were associated with new onset depression. [ABSTRACT FROM AUTHOR]

and Purpose Volatile organic compounds (VOCs) pose a serious respiratory hazard. This study evaluated the relationship between the compositional patterns of blood VOCs and the risk and age at onset of chronic respiratory diseases (CRDs), including asthma, emphysema and chronic bronchitis, with the objective of preventing or delaying CRDs. Participants from five cycles of the NHANES survey were included. Blood VOCs were clustered using k-means clustering. Differences in VOCs and age at onset between multiple groups were compared with the Kruskal‒Wallis test. Logistic regression and a generalized linear model were applied to examine the associations between different compositional patterns of blood VOCs and risk and age at onset of CRDs. 12,386 participants were enrolled in this study. Three VOC compositional patterns were identified after clustering nine species of blood VOCs. The concentration of VOCs in pattern 2 was relatively low and stable. The concentrations of benzene, ethylbenzene, o-xylene, styrene, toluene and m-p-xylene in pattern 3 and the concentrations of 1,4-dichlorobenzene and MTBE in pattern 1 were significantly higher than those in pattern 2. After adjustment for covariates, the participants with VOC pattern 3 had an increased risk of asthma (OR = 1.23, 95% CI: 1.02, 1.49), emphysema (OR = 3.37, 95% CI: 2.24, 5.06) and chronic bronchitis (OR = 1.79, 95% CI: 1.30, 2.45). Meanwhile, VOC pattern 3 was negatively correlated with the age at onset of asthma (β = −5.61, 95% CI: 9.69, −1.52) and chronic bronchitis (β = −9.17, 95% CI: 13.96, −4.39). VOC pattern 1 was not associated with either risk or age at onset of the three CRDs after adjustment. Changing the compositional pattern of blood VOCs by reducing certain species of VOCs may be a new strategy to lengthen the ages at onset of CRDs and effectively prevent them. [Display omitted] • Blood VOCs in the U.S. population show 3 main composition patterns. • Different compositional patterns of blood VOCs show different relations with CRDs. • Changing the compositional pattern of VOCs may prevent or delay the onset of CRDs. [ABSTRACT FROM AUTHOR]

Background Cystic fibrosis (CF) is the most common inherited disease in Caucasians, affecting around 10,000 individuals in the UK today. Prognosis has improved considerably over recent decades with ongoing improvements in treatment and care. Providing up-to-date survival predictions is important for patients, clinicians and health services planning. Methods Flexible parametric survival modelling of UK CF Registry data from 2011 to 2015, capturing 602 deaths in 10,428 individuals. Survival curves were estimated from birth; conditional on reaching older ages; and projected under different assumptions concerning future mortality trends, using baseline characteristics of sex, CFTR genotype (zero, one, two copies of F508del) and age at diagnosis. Findings Male sex was associated with better survival, as was older age at diagnosis, but only in F508del non-homozygotes. Survival did not differ by genotype among individuals diagnosed at birth. Median survival ages at birth in F508del homozygotes were 46 years (males) and 41 years (females), and similar in non-homozygotes diagnosed at birth. F508del heterozygotes diagnosed aged 5 had median survival ages of 57 (males) and 51 (females). Conditional on survival to 30, median survival age rises to 52 (males) and 49 (females) in homozygotes. Mortality rates decreased annually by 2% during 2006–2015. Future improvements at this rate suggest median survival ages for F508del homozygous babies of 65 (males) and 56 (females). Interpretation Over half of babies born today, and of individuals aged 30 and above today, can expect to survive into at least their fifth decade. Research in context Evidence before this study We searched PubMed with terms “(cystic fibrosis survival) and (projection OR model OR registry OR United Kingdom OR UK)” to identify relevant studies on survival estimates for individuals with cystic fibrosis (CF). We also considered the most recent annual report from the UK Cystic Fibrosis Registry (Cystic Fibrosis Trust, 2016), a review by Buzzetti and colleagues (2009), the chapter on Epidemiology of Cystic Fibrosis by MacNeill (2016), the study of MacKenzie and colleagues (2014), and references therein. There have been many studies of factors associated with survival in CF; most have focused on identifying risk factors, and only a few have presented estimated survival curves, which are the focus of this work. The most recent study of survival in the UK is by Dodge and colleagues (2007), who used data obtained from CF clinics and the national death register, and gave an estimate of survival for babies born in 2003. We found no previous studies that have obtained detailed information on survival using UK Cystic Fibrosis Registry data. Jackson and colleagues obtained survival estimates for the US and Ireland using registry data (Jackson et al., 2011). MacKenzie and colleagues used US Cystic Fibrosis Foundation Patient Registry data from 2000 to 2010 to project survival for children born and diagnosed with CF in 2010, accounting for sex, genotype and age at diagnosis (MacKenzie et al., 2014). Previous studies on estimated survival in CF have become out of date or have not accounted for the full range of patient characteristics available at birth. Few have presented conditional survival estimates (Dodge et al., 2007). Added value of this study This is the first study to yield detailed survival statistics using the UK Cystic Fibrosis Registry, which is one of the largest national CF registries outside of the US and has almost complete coverage of the UK CF population. The primary goal was to leverage the long-term follow-up of the nearly complete UK CF population available in the Registry for the purposes of producing accurate, precise predictions in the modern era of CF care. Estimates are presented from birth and conditional on survival to older ages. These are the first conditional estimates in CF to also account for genotype, sex and age at diagnosis, which were each included in the modelling using a flexible approach. Projections are also provided under different scenarios based on downward trends in mortality rates. Our use of flexible parametric survival models is novel in this field, and our approach could be used to provide modern survival statistics for other chronic diseases and disorders. Implications of all the available evidence Our estimates of future survival in CF under a range of different scenarios are based on data on nearly all individuals living with the disease in the UK in recent times, reflective of a modern era of care, and are most appropriate for the families of babies being born in the present day with CF. Conditional estimates inform patients who have already reached an older age, and their clinicians. Over half of babies born today, and of individuals aged 30 years and above alive today, can expect to survive into their fifth decade. Insights based on our survival projections can be used to inform future needs in CF health care provision. [ABSTRACT FROM AUTHOR]

Background Gait abnormalities have been seen in patients with Parkinson disease or Parkinson-like (P-L) disorders and cervical spinal stenosis. Acute presentation of P-L symptoms has been reported in 24 cases caused by chronic subdural hematomas with 11 cases due to bilateral chronic subdural hematomas. When a patient also presents with cervical spinal stenosis, the correct therapeutic decision between P-L disorders and myelopathy is challenging. Case Description An 80-year-old male presented with a 2-week history of weakness in his left leg. A few days before presentation, his gait had deteriorated quite dramatically. Neurologic examination showed mild leg weakness, hyperreflexia, and a gait that was slow and wide based, at times festinating but with relatively spared arm movement. He also had masked facial features with increased tone in his extremities. Magnetic resonance imaging of the cervical spine showed cervical stenosis at C5-6, and computed tomography of the head showed large bilateral subdural hematomas. The subdural hematomas were drained. Immediate improvement in his symptoms was observed with complete resolution by his third month of follow-up. The patient never had a history of Parkinson disease. Conclusions This paper reports for the first time a patient who presented with acute P-L symptoms and cervical myelopathy with findings of both bilateral chronic subdural hematomas and cervical spinal stenosis. The decision to drain the subdural hematoma in our case resulted in full recovery of the patient's gait and other extrapyramidal symptoms. This paper reviews the literature on reversible P-L symptoms caused by bilateral chronic subdural hematomas. [ABSTRACT FROM AUTHOR]

Background: There are only few data on medical problems and utilization of health services of former very low birth weight (VLBW) children at preschool age.Study Design: At five years of age parents of a cohort of VLBW children (N=862) received questionnaires, a medical interview and examination. The results were compared to the KIGGS cohort (Deutscher-Kinder-und Jugendgesundheitssurvey, N=777).Results: Parents of the VLBW and KIGGS cohort reported a very good or good health in 95% in their children. When compared to the KIGGS cohort, families in the VLBW cohort had a lower social economic status. The VLBW cohort suffered more frequently from disabilities (9.6% vs. 1.4%), from chronic bronchitis (45% vs. 17%) and from recurrent pain (headaches (20% vs. 7%), ear (16% vs. 6%), throat (23% vs. 8%), tooth (10% vs. 3%)). The VLBW cohort received more specialized care (ophthalmologist, ENT, orthopaedics, paediatric neurologist).Conclusion: Families of VLBW children report a good health status in their children, but they utilized more specialized care. Higher rates of pain are reported in the VLBW cohort. Chronic bronchitis and various upper respiratory infections cause an increased morbidity in former VLBW children. Follow up programs are needed to develop optimal treatment and prevention strategies for these problems. [ABSTRACT FROM AUTHOR]

Yu Ping Feng San (YPFS) is a classical TCM formulation which has been traditionally used for treatment of immune system related diseases such as chronic bronchitis, allergic rhinitis and asthma. The formula is a mixture of Radix Saposhnikoviae (Fangfeng), Radix Astragali (Huangqi), and Rhizoma Atractylodis macrocephalae (Baizhu). TLC- and LC-DAD-ESI-MS/MS methods have been developed for the analysis of the metabolic profiles of the single herbs and of the formula. Decoctions and ASE extracts were analyzed in order to trace components of the individual herbs in YPFS. Nine constituents of Radix Saposhnikoviae, ten constituents of Radix Astragali and five constituents of Rhizoma Atractylodis macrocephalae have been assigned in the chemical profiles of the formula, which now allow the standardisation of YPFS. The pharmacological testing showed that all extracts significantly inhibited expression of TNF-α, IFN-γ, and IL-1β in U937 cells, while the inhibition of IL-4 was consistently low. Compared to conventional analyses which are focused on a limited set of compounds, metabolomics approaches, together with novel data processing tools, enable a more holistic comparison of the herbal extracts. In order to identify the constituents which are relevant for the immunomodulatory effects of the formula, metabolomics studies (PCA, OPLS-DA) have been performed using UPLC/QTOF MS data. [ABSTRACT FROM AUTHOR]

Chronic bronchitis (CB) affects a growing number of people and may be linked to lung function impairment. The traditional Chinese medicine formula Houpo Mahuang Decoction (HPMHD) has been used for clinical treatment of respiratory diseases for thousands of years. Until now, its bioactive ingredients, potential targets and molecular mechanism remain unclear. To investigate the effect of HPMHD on the treatment of CB and explore the bioactive ingredients and possible mechanisms of HPMHD against CB. UHPLC-Q Exactive Orbitrap HRMS was performed to analyze the chemical components of HPMHD. The mechanism of multiple components, targets and pathways of HPMHD in the treatment of chronic bronchitis were explored by network pharmacology. Additionally, CB mice model induced by lipopolysaccharide (LPS) and smoking was used to evaluate the anti-chronic bronchitis activity of HPMHD in vivo. Pulmonary pathology was determined by hematoxylin and eosin (H&E) measurement. The levels of TNF- α and IL-6 in lung were measured by ELISA. The immunofluorescence experiments were carried out for the expression of IL-1 β , TNF- α , IL-6 and NF-κB p-P65/P65 in lung. Western blot assays were performed to quantify and visualize the protein expression of NF-κB p-P65/P65 in mice lung. Data showed that 79 compounds were identified in HPMHD. The network pharmacology results showed 53 compounds were hinted their effectivity for the treatment of chronic bronchitis with HPMHD, such as ephedrine, schisantherin A, and honokiol. The main targets were predicted as 37 genes, including TNF, TP53, IL6 and so on. HPMHD ameliorated lung damages in mice and inhibited the NF-κB signaling pathway, one of the pathways plotted by KEGG pathway enrichment analysis, by reducing IL-1 β , TNF- α and IL-6 expression and significantly downregulating the NF-κB p-P65/P65. In summary, the complex chemical components of HPHMD was successfully elucidate by UHPLC-Q Exactive Orbitrap HRMS. The study based on network pharmacology and experiment verification indicated that HPMHD can decreased inflammatory response in lung to treat CB. The underlying mechanism may be related to the reduction of inflammation by down-regulated the NF-κB pathways. [Display omitted] • 79 compounds in Houpo Mahuang Decoction (HPHMD) were identified by UHPLC-Q Exactive Orbitrap HRMS. • Network pharmacology revealed that NF-κB pathway was an important pathway for treatment of chronic bronchitis with HPMHD. • HPMHD improved lung damages in mice by down-regulating the level of NF-κB p -P65/P65. [ABSTRACT FROM AUTHOR]

Inflammatory processes are putative mechanisms underlying chronic disease. In this study we explore linear and non-linear associations between personality and change in inflammatory markers (C–reactive protein [CRP], fibrinogen, and white blood cell count [WBC]). In total, 5294 older adults ( M age = 64.51 ± 8.34 years) provided blood samples in 2008 with 3751 providing follow-up samples four year later. Midway between the two assessments, participants completed a measure of personality. After controlling for participant demographics (e.g., age, gender) and health-related lifestyle factors (e.g., exercise, cigarette smoking), we found that higher levels of agreeableness and lower levels of conscientiousness were associated with higher CRP levels, and (for conscientiousness) an increase in CRP over time. Age moderation effects indicated that agreeableness and conscientiousness were related to WBC among older participants in the sample (over ~ 70 years of age). These findings provide evidence that agreeableness and conscientiousness traits are important for inflammatory biomarkers in older adulthood. [ABSTRACT FROM AUTHOR]

Airways diseases, especially chronic obstructive pulmonary disease (COPD) and asthma, are common causes of morbidity and mortality worldwide. There is an ongoing unmet need for novel and effective therapies. There is an established pathophysiological link and phenotypic similarity between the chronic bronchitis phenotype of COPD and cystic fibrosis (CF). New evidence suggests that CFTR dysfunction may play a role in other common airways diseases such as COPD, non-atopic asthma and non-CF bronchiectasis. Newly approved and investigational drugs that target both mutant and wild-type CFTR channels have provided a new treatment opportunity addressing the mucus defect in pulmonary diseases that share the same pathophysiology with CF. [ABSTRACT FROM AUTHOR]

Background The presence of a bifurcation (BL) in the context of a coronary chronic total occlusion (CTO) represents an additional difficulty. This study analyzes the incidence of BLs in CTO recanalization, the treatment, predictors of bifurcation technical success and their clinical impact. Methods and results BLs with a side branch (SB) ≥ 2.0 mm located proximally, distally or within the occluded segment were observed in 130 (33%) of 391 CTO. Provisional stenting was the strategy more frequently used (94%). Bifurcation success (stenosis < 30% in main vessel and TIMI flow III in both branches) was achieved in 105 patients (81%). In the remaining 25 (19%), the TIMI flow at the SB was < III. Predictors of bifurcation success were baseline SB wiring (OR 0.01, 95% CI: 0.001–0.09; p < 0.01), the absence of dissection across the bifurcation (OR 0.10, 95% CI: 0.02–0.49; p < 0.01) and non-true BLs (OR 0.16, 95% CI: 0.04–0.68; p < 0.05). Regarding in-hospital results, patients with final TIMI flow < III at the SB had a higher incidence of periprocedural MI (32% vs 4.8%; p < 0.01). Subsequently, the rate of MI was higher in patients with CTO-BLs than in those without BLs. At follow-up, there were no differences in the event rate between CTO-BLs and non CTO-BLs (7.7% vs 9.5%, p = ns) Conclusions BLs in CTO is a frequent finding and could be approached as regular bifurcations. The primary success was low and this was associated with a higher incidence of periprocedural MI. Baseline SB wiring was a powerful predictor of technical success. [ABSTRACT FROM AUTHOR]

Background: Airway clearance techniques include positive expiratory pressure, commonly used in our clinical practice, and a recently introduced temporary positive expiratory pressure device called UNIKO®. It is unclear which one provides the best benefit to patients. Objectives: The aim of this observational 4-year study was to retrospectively compare the efficacy of and specific indications for temporary positive expiratory pressure compared to positive expiratory pressure in a standard rehabilitation program. Method: We retrospectively collected data from 162 subjects (107 males, mean age 70±9 years, 97 with primary diagnosis of chronic obstructive pulmonary disease, 65 with bronchiectasis), 51 treated with temporary positive expiratory pressure and 111 with positive expiratory pressure. Results: Subjects showed significant improvement in ratio of partial pressure arterial oxygen and fraction of inspired oxygen (p < 0.001), forced vital capacity, forced expiratory volume in one second, peak expiratory flow, arterial oxygen saturation, and partial pressure arterial oxygen with no significant difference between positive expiratory pressure and temporary positive expiratory pressure groups apart from forced expiratory flow, which increased only in the positive expiratory pressure group. Evaluating specific subgroups, temporary positive expiratory pressure was more effective than positive expiratory pressure in improving gas transfer in subjects with emphysema and in those on oxygen therapy, as the effective supplement oxygen flow decreased significantly (p = 0.034 and 0.046 respectively for temporary positive expiratory pressure vs. positive expiratory pressure). In subjects on mechanical ventilation, positive expiratory pressure was superior to temporary positive expiratory pressure in increasing forced expiratory flow (p = 0.018). Conclusion: The physiological parameters of both groups improved significantly and similarly. Subgroup analysis suggests that temporary positive expiratory pressure could provide some advantage to subjects with emphysema and those on oxygen therapy, while positive expiratory pressure would benefit patients on mechanical ventilation. Randomized clinical trials are necessary to confirm our preliminary results indicating that different subgroups/phenotypes can benefit more from one type of treatment. [ABSTRACT FROM AUTHOR]

Although spirometry is a simple, portable test and recommended for the diagnosis of asthma and chronic obstructive pulmonary disease (COPD), it is not routinely used in the primary care setting. Minorities and underserved populations are less likely to have spirometry assessment, leading to both over and misdiagnosis of asthma and COPD. Because dyspnea is a common symptom across multiple diseases, use of spirometry as a diagnostic tool is important. Missed, delayed, or misdiagnosis of asthma and COPD, which are considered diagnostic errors (DE), can lead to poor quality of care, increased morbidity and mortality, and increased costs to patients and health systems. Barriers to the use of spirometry have been identified at clinician/clinic and health systems levels. The REDEFINE program is designed to overcome identified barriers to spirometry use in primary care by utilizing health promoters (HPs) who perform spirometry within primary care clinics and work collaboratively with clinicians to incorporate the results at the point of care without interrupting clinic workflow. The REDEFINE trial is a comparative effectiveness study comparing outcomes of the REDEFINE program with usual care (UC) in primary care patients determined to be at increased risk of DE for asthma and COPD. The primary outcome will be all-cause hospitalizations. The secondary outcomes will be the proportion of accurate diagnosis of COPD, asthma, or asthma-COPD overlap based on initial diagnosis and spirometry and all cause and respiratory-related acute outpatient care and emergency department visits. In this report, we describe the design and methods for the REDEFINE trial. Trial registration: NCT03137303 https://clinicaltrials.gov/ct2/show/NCT03137303?term=REDEFINE&draw=2&rank=1 [ABSTRACT FROM AUTHOR]

• 2,4-Dibromoaniline is the core chromophore of ambroxol. • Exposure to UV 254 resulted in debromination of ambroxol and 2,4-dibromoaniline. • The para -Br is more vulnerable toward photo-debromination. • A total of 12 photoproducts were identified. • Bioluminescence inhibition assay revealed that photoproducts were not toxic. As one of the most effective expectorant class drugs, ambroxol (AMB) has been frequently used to treat acute and chronic bronchitis. Extensive use and human excretion result in the widespread occurrence of AMB in wastewater. Herein, we reported the photolysis of AMB in aqueous solution upon 254 nm ultraviolet radiation (UV 254). Spectroscopic characterization showed that 2,4-dibromoaniline (DBA) moiety is the core chromophore of AMB. Quantum yield of DBA changed little at pH 4.0 - 9.0; however, AMB showed higher quantum yield at pH > 8.0. Both DBA and AMB have high photoreactivity, which can be attributed to the "heavy atom" effect of bromine substituents. The photolysis of AMB occurred through photoreduction, photoionization, photonucleophilic substitution, side-chain cleavage, and coupling reactions. Both AMB and DBA underwent debromination with yields reaching 80% under 3200 mJ cm−2 UV fluence. Photo-debromination occurred preferentially at the para -position. The presence of natural organic matter inhibited the photodegradation, mainly due to the light-screening effect. The photolysis of AMB was slightly enhanced in the presence of NO 3 − likely due to radical-induced oxidation. Bioluminescence inhibition assay revealed that photoproducts were not toxic. The results show that UV 254 radiation with fluences relevant to advanced oxidation processes was effective for the abatement of AMB in wastewater. However, UV 254 treatment of wastewater containing higher concentrations (˃ μg L−1) of AMB should be done with caution because the released Br− can be converted to toxic brominated disinfection byproducts and bromate in subsequent oxidation process. [Display omitted] [ABSTRACT FROM AUTHOR]

Background Several studies highlighted a great variability, both between and within countries, in the prevalence of asthma and chronic airways diseases. Aim To evaluate if geo-climatic variations can explain the heterogeneity in the prevalence of asthma and respiratory diseases in Italy. Methods Between 2006 and 2010, a postal screening questionnaire on respiratory health was administered to 18,357 randomly selected subjects, aged 20–44, living in 7 centers in northern, central, and southern Italy. A random-effects meta-analysis was fitted to evaluate the between-centers heterogeneity in the prevalence of asthma, asthma-like symptoms, allergic rhinitis, and chronic bronchitis (CB). A principal component analysis (PCA) was performed to synthetize the geo-climatic information (annual mean temperature, range of temperature, annual rainfalls, global solar radiations, altitude, distance from the sea) of all the 110 Italian province capital towns. The associations between these geo-climatic components obtained with PCA and the prevalence of respiratory diseases were analyzed through meta-regression models. Results 10,464 (57%) subjects responded to the questionnaire. There was a significant between-centers heterogeneity in the prevalence of asthma (I 2 = 59.5%, p = 0.022) and CB (I 2 = 60.5%, p = 0.019), but not in that of asthma-like symptoms or allergic rhinitis. Two independent geo-climatic components explaining together about 80% of the overall geo-climatic variability were identified: the first principally summarized the climatic variables; the second the topographic ones. Variations in the prevalence of asthma across centers were significantly associated with differences in the climatic component (p = 0.017), but not with differences in the topographic one. Conclusions Our findings suggest that climate play a role in determining the between-center heterogeneity in the prevalence of asthma in Italy, with higher prevalence in dry-hot Mediterranean climates, and lower in rainy-cold northern climates. [ABSTRACT FROM AUTHOR]

Background Serum cytokeratin fragment 21-1 (CYFRA 21-1) expression levels are reported to be useful in the diagnosis of lung cancer, especially non-small cell lung cancer (NSCLC). However, the clinical value of CYFRA 21-1 as a tumor marker remains unclear, and no optimal cut-off value has been determined thus far. The purpose of this study was to establish a potential clinical cut-off value for serum CYFRA 21-1 as a diagnostic marker in patients with NSCLC. Methods A total of 90 patients with NSCLC, 237 patients with benign pulmonary disease (BPD), and 1296 healthy controls were enrolled in this study. Among BPD there are 84 with chronic obstructive pulmonary disease (COPD), 81 with pneumonia, 38 with tuberculosis and 34 with chronic bronchitis. CYFRA 21-1 was measured in sera with an electrochemiluminescence (ECL) E170 analyzer. Comparisons were conducted using the chi-squared test and the Mann–Whitney test (two-sided). A receiver operating characteristic (ROC) curve was constructed to investigate the diagnostic power of CYFRA 21-1 expression, and the recommended cut-off value was chosen to calculate its sensitivity and specificity. Results The cut-off values of CYFRA 21-1 in NSCLC by the ROC curve were 4.70 ng/mL when compared with COPD, which was obviously greater than that found with pneumonia (2.79 ng/mL) (P < 0.05), tuberculosis (2.66 ng/mL) (P < 0.05), and chronic bronchitis (3.94 ng/mL) (P < 0.05) patients. Therefore, a cut-off value of 4.24 ng/mL in NSCLC was suggested. Conclusions The presence of various BPDs may be one of the main reasons that no optimal cut-off value for CYFRA 21-1 expression in NSCLC has been determined previously. [ABSTRACT FROM AUTHOR]