Efficacy and safety of caspofungin for the treatment of invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease.

OBJECTIVES: We assessed the efficacy of a 3-week primary or salvage caspofungin regimen in patients with chronic obstructive pulmonary disease (COPD) and concomitant proven or suspected invasive pulmonary aspergillosis (IPA). METHODS: Forty-four patients were treated with an initial loading caspofungin dose of 70 mg, followed by a daily dose of 50 mg for 20 days. The main efficacy endpoint was clinical effectiveness. Secondary endpoints included the clinical efficacy of caspofungin after 1 week, therapeutic efficacy based on the European Organization for Research and Treatment of Cancer and Mycoses Study Group Education and Research Consortium (EORTC/MSG) criteria, the sensitivity of different Aspergillus strains to caspofungin in vitro, and the safety of caspofungin. RESULTS: An assessment of 42 patients in the intention-to-treat group revealed efficacy rates of 33.33% within 1 week and 38.10% within 3 weeks. According to the EORTC/MSG criteria, the treatment success rate was 38.10%. The success rate of first-line treatment was 54.76%, whereas salvage treatment had a success rate of 45.24%. No adverse events were reported among the participants. CONCLUSIONS: Caspofungin is effective and safe as an initial or salvage treatment for patients with IPA and COPD.

Profiles of Cough and Associated Risk Factors in Nonhospitalized Individuals With SARS-CoV-2 Omicron Variant Infection: Cross-Sectional Online Survey in China.

BACKGROUND: Cough is a common symptom during and after COVID-19 infection; however, few studies have described the cough profiles of COVID-19. OBJECTIVE: The aim of this study was to investigate the prevalence, severity, and associated risk factors of severe and persistent cough in individuals with COVID-19 during the latest wave of the Omicron variant in China. METHODS: In this nationwide cross-sectional study, we collected information of the characteristics of cough from individuals with infection of the SARS-CoV-2 Omicron variant using an online questionnaire sent between December 31, 2022, and January 11, 2023. RESULTS: There were 11,718 (n=7978, 68.1% female) nonhospitalized responders, with a median age of 37 (IQR 30-47) years who responded at a median of 16 (IQR 12-20) days from infection onset to the time of the survey. Cough was the most common symptom, occurring in 91.7% of participants, followed by fever, fatigue, and nasal congestion (68.8%-87.4%). The median cough visual analog scale (VAS) score was 70 (IQR 50-80) mm. Being female (odds ratio [OR] 1.31, 95% CI 1.20-1.43), having a COVID-19 vaccination history (OR 1.71, 95% CI 1.37-2.12), current smoking (OR 0.48, 95% CI 0.41-0.58), chronic cough (OR 2.04, 95% CI 1.69-2.45), coronary heart disease (OR 1.71, 95% CI 1.17-2.52), asthma (OR 1.22, 95% CI 1.02-1.46), and gastroesophageal reflux disease (GERD) (OR 1.21, 95% CI 1.01-1.45) were independent factors for severe cough (VAS>70, 37.4%). Among all respondents, 35.0% indicated having a productive cough, which was associated with risk factors of being female (OR 1.44, 95% CI 1.31-1.57), having asthma (OR 1.84, 95% CI 1.52-2.22), chronic cough (OR 1.44, 95% CI 1.19-1.74), and GERD (OR 1.22, 95% CI 1.01-1.47). Persistent cough (>3 weeks) occurred in 13.0% of individuals, which was associated with the risk factors of having diabetes (OR 2.24, 95% CI 1.30-3.85), asthma (OR 1.70, 95% CI 1.11-2.62), and chronic cough (OR 1.97, 95% CI 1.32-2.94). CONCLUSIONS: Cough is the most common symptom in nonhospitalized individuals with Omicron SARS-CoV-2 variant infection. Being female, having asthma, chronic cough, GERD, coronary heart disease, diabetes, and a COVID-19 vaccination history emerged as independent factors associated with severe cough, productive cough, and persistent cough.

Efficacy of dupilumab and risk factors for dupilumab-induced hypereosinophilia in severe asthma: a preliminary study from China.

OBJECTIVE: Dupilumab has been approved for the treatment of severe asthma with type 2 inflammation by inhibiting interleukin (IL)-4 and IL-13 signaling. However, dupilumab-induced hypereosinophilia (HE) has been reported and should not be ignored. The aim of this study was to investigate the efficacy of dupilumab in Chinese patients with severe asthma, whether HE affects its efficacy, and the possible risk factors for HE. METHODS: 20 patients with severe asthma who received dupilumab treatment for at least 12 months in the First Affiliated Hospital of Guangzhou Medical University from 2019 to 2022 were included. We compared clinical data and laboratory tests results before dupilumab treatment and at 4 and 12 months after treatment. Based on whether dupilumab treatment triggers HE defined as blood eosinophil count (BEC) ≥ 1.5 × 109 cells/L, the patients were allocated into non-HE and HE groups. RESULTS: The patients showed a significant increase in asthma control test (ACT) scores, a decrease in the number of exacerbations, a decrease in the proportion of patients taking an oral corticosteroid (OCS) and in the dose, and a significant improvement in the pulmonary function parameters FEV1/FVC (%) and FEV1 (% predicted) after 4 and 12 months of treatment with dupilumab. For type 2 inflammatory biomarkers, the levels of fractional concentration of exhaled nitric oxide (FeNO), sputum eosinophil count percentage (SEC%) and total immunoglobulin E (TIgE) decreased significantly, whereas BEC were higher after 4 months of treatment, but returned to baseline levels after 12 months. 8 patients (40%) developed asymptomatic HE after dupilumab, and the efficacy was not significantly different between the HE and non-HE groups. The earliest BEC elevation appeared at 1 month after treatment, but most of them declined after 6 months, and basically returned to the baseline level around 12 months of treatment. In addition, we further found that when patients had FeNO ≥ 60 ppb, food allergens positive and combined eosinophilic otitis media (EOM), their BEC increased significantly more than that of the control group after 4 months as well as 12 months of treatment. CONCLUSIONS: This study demonstrated that dupilumab was efficacious in Chinese patients with severe asthma, and some patients developed asymptomatic, self-limited HE, which did not affect its efficacy. Additionally, FeNO ≥60 ppb, food allergens positive, and co-morbidities with EOM may be the risk factors for developing HE.

Fine particulate matter contributes to COPD-like pathophysiology: experimental evidence from rats exposed to diesel exhaust particles.

BACKGROUND: Ambient fine particulate matter (PM2.5) is considered a plausible contributor to the onset of chronic obstructive pulmonary disease (COPD). Mechanistic studies are needed to augment the causality of epidemiologic findings. In this study, we aimed to test the hypothesis that repeated exposure to diesel exhaust particles (DEP), a model PM2.5, causes COPD-like pathophysiologic alterations, consequently leading to the development of specific disease phenotypes. Sprague Dawley rats, representing healthy lungs, were randomly assigned to inhale filtered clean air or DEP at a steady-state concentration of 1.03 mg/m3 (mass concentration), 4 h per day, consecutively for 2, 4, and 8 weeks, respectively. Pulmonary inflammation, morphologies and function were examined. RESULTS: Black carbon (a component of DEP) loading in bronchoalveolar lavage macrophages demonstrated a dose-dependent increase in rats following DEP exposures of different durations, indicating that DEP deposited and accumulated in the peripheral lung. Total wall areas (WAt) of small airways, but not of large airways, were significantly increased following DEP exposures, compared to those following filtered air exposures. Consistently, the expression of α-smooth muscle actin (α-SMA) in peripheral lung was elevated following DEP exposures. Fibrosis areas surrounding the small airways and content of hydroxyproline in lung tissue increased significantly following 4-week and 8-week DEP exposure as compared to the filtered air controls. In addition, goblet cell hyperplasia and mucus hypersecretions were evident in small airways following 4-week and 8-week DEP exposures. Lung resistance and total lung capacity were significantly increased following DEP exposures. Serum levels of two oxidative stress biomarkers (MDA and 8-OHdG) were significantly increased. A dramatical recruitment of eosinophils (14.0-fold increase over the control) and macrophages (3.2-fold increase) to the submucosa area of small airways was observed following DEP exposures. CONCLUSIONS: DEP exposures over the courses of 2 to 8 weeks induced COPD-like pathophysiology in rats, with characteristic small airway remodeling, mucus hypersecretion, and eosinophilic inflammation. The results provide insights on the pathophysiologic mechanisms by which PM2.5 exposures cause COPD especially the eosinophilic phenotype.

Citrus peel extract protects against diesel exhaust particle-induced chronic obstructive pulmonary disease-like lung lesions and oxidative stress.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide and characterized by emphysema, small airway remodeling and mucus hypersecretion. Citrus peels have been widely used as food spices and in traditional Chinese medicine for chronic lung disease. Given that citrus peels are known for containing antioxidants and anti-inflammatory compounds, we hypothesize that citrus peel intake can suppress oxidative stress and inflammatory response to air pollution exposure, thereby alleviating COPD-like pathologies. This study aimed to investigate the efficacy of citrus peel extract, namely Guang Chenpi (GC), in preventing the development of COPD induced by diesel exhaust particles (DEPs) and its potential mechanism. DEP-induced COPD-like lung pathologies, inflammatory responses and oxidative stress with or without GC treatment were examined in vivo and in vitro. Our in vivo study showed that GC was effective in decreasing inflammatory cell counts and inflammatory mediator (IL-17A and TNF-α) concentrations in bronchoalveolar lavage fluid (BALF). Pretreatment with GC extract also significantly decreased oxidative stress in the serum and lung tissue of DEP-induced COPD rats. Furthermore, GC pretreatment effectively reduced goblet cell hyperplasia (PAS positive cells) and fibrosis of the small airways, decreased macrophage infiltration as well as carbon loading in the peripheral lungs, and facilitated the resolution of emphysema and small airway remodeling in DEP-induced COPD rats. An in vitro free radical scavenging assay revealed robust antioxidant potential of GC in scavenging DPPH free radicals. Moreover, GC demonstrated potent capacities in reducing ROS production and enhancing SOD activity in BEAS-2B cells stimulated by DEPs. GC treatment significantly attenuated the increased level of IL-8 and MUC5AC from DEP-treated BEAS-2B cells. Mechanistically, GC treatment upregulated the protein level of Nrf-2 and could function via MAPK/NF-κB signaling pathways by suppressing the phosphorylation of p38, JNK and p65. Citrus peel extract is effective in decreasing oxidative stress and inflammatory responses of the peripheral lungs to DEP exposure. These protective effects further contributed to the resolution of COPD-like pathologies.

Characteristics of patients with incidental eosinophilia admitted to a tertiary hospital in southern China.

Background: The characteristics of patients with eosinophilia are heterogeneous and the outcomes can vary from asymptomatic to severe. Objective: To describe the feature of patients with eosinophilia in a single center. Design: Based on the electronic medical records from Yangjiang People's Hospital in China, the inpatients admitted between June 2018 and February 2021 with measured blood eosinophil counts were evaluated. Methods: Eosinophilia was defined as a peripheral blood eosinophil count of ≥0.5 × 109/L. Differences were compared by eosinophilia severity. The medical records of patients with moderate to severe eosinophilia were reviewed and summarized in terms of examination, diagnoses and management. And these patients were matched with patients without incidental eosinophilia by propensity score and the differences were compared. Results: A total of 7,835 patients with eosinophilia were identified out of 131,566 total inpatients. All types of eosinophilia were most common in males (8.2%; 5,351/65,615), and in patients aged 0-6 years (11.6%; 1,760/15,204), and in the pediatric (10.8%; 1,764/16,336) department, followed by dermatology (10.6%; 123/1,162), Oncology (7.5%; 394/5,239) and Intensive care unit (ICU) (7.4%; 119/1,608). Patients with moderate to severe eosinophilia were more likely to admit to ICU (moderate: 1.3%; severe: 0.50%). In patients with moderate to severe eosinophilia, only 205/621 (33%) had eosinophilia mentioned in their records, and only 63/621 (10.1%) underwent investigations for eosinophilia. The majority of patients with moderate to severe eosinophilia (372/621, 59.9%) had an infectious disease, and little examination (7.4%; 46/621) was taken to identify the cause of eosinophilia, and only 39/621 (6.3%) of patients had a discrete cause of eosinophilia identified. Patients with moderate to severe eosinophilia (24.3%; 151/621) exhibited certain chance to have organ dysfunction. Conclusion: Incidental eosinophilia in inpatients was frequently neglected and less investigated. Multidisciplinary consultation may improve outcomes of inpatients with moderate to severe eosinophilia.

Identification of cough-variant asthma phenotypes based on clinical and pathophysiologic data.

BACKGROUND: Cough-variant asthma (CVA) may respond differently to antiasthmatic treatment. There are limited data on the heterogeneity of CVA. OBJECTIVE: We aimed to classify patients with CVA using cluster analysis based on clinicophysiologic parameters and to unveil the underlying molecular pathways of these phenotypes with transcriptomic data of sputum cells. METHODS: We applied k-mean clustering to 342 newly physician-diagnosed patients with CVA from a prospective multicenter observational cohort using 10 prespecified baseline clinical and pathophysiologic variables. The clusters were compared according to clinical features, treatment response, and sputum transcriptomic data. RESULTS: Three stable CVA clusters were identified. Cluster 1 (n = 176) was characterized by female predominance, late onset, normal lung function, and a low proportion of complete resolution of cough (60.8%) after antiasthmatic treatment. Patients in cluster 2 (n = 105) presented with young, nocturnal cough, atopy, high type 2 inflammation, and a high proportion of complete resolution of cough (73.3%) with a highly upregulated coexpression gene network that related to type 2 immunity. Patients in cluster 3 (n = 61) had high body mass index, long disease duration, family history of asthma, low lung function, and low proportion of complete resolution of cough (54.1%). TH17 immunity and type 2 immunity coexpression gene networks were both upregulated in clusters 1 and 3. CONCLUSION: Three clusters of CVA were identified with different clinical, pathophysiologic, and transcriptomic features and responses to antiasthmatics treatment, which may improve our understanding of pathogenesis and help clinicians develop individualized cough treatment in asthma.

Effects of tea saponin on the foaming properties of pea protein.

Plant proteins are becoming increasingly important for foam formation as an alternative to animal proteins. Consumers, however, are unsatisfied with the foaming properties of pea protein isolates. Recent research on proteins and surfactants has primarily concentrated on chemically synthesized surfactants. In this study, foams were prepared by complexing pea protein isolates with a natural small molecule surfactant tea saponin. This study investigates the mechanisms responsible for the formation and stability of foams prepared from pea protein isolates (PPIs) complexed with tea saponins. Analyses of foaming performance were carried out by analyzing the morphology of foam, foaming properties, foam's rheological properties, and the microstructure of the pea protein-tea saponin complex system. Compared to the pea protein isolate alone, the pea protein-tea saponin complex significantly improved foaming capacity and foaming stability. As shown by light microscopy analysis, the size of the foam decreased and became more homogeneous, probably because of the altered aggregate state of the protein. In this study, natural surfactants and mixtures of plant proteins are studied in order to better understand their properties. The mixed system has excellent prospects for application in the industries related to foam.

Low human beta-defensin-2 levels in the sputum of COPD patients are associated with the risk of exacerbations.

RATIONALE: Chronic obstructive pulmonary disease (COPD) is a complicated chronic inflammatory disease. It is important to investigate the characteristics of acute exacerbation of COPD to develop new therapeutic strategies. OBJECTIVE: This study aimed to determine the relationship between the human beta-defensin-2 (hBD-2) levels and aggravation of COPD. METHODS: We detected the sputum hBD-2 level of 254 patients from Guangzhou, China, for 2 years. The study participants were categorized into the COPD group (n = 203, GOLD 0-4) and the control group (n = 51, 40-79 years old). At baseline, 12th month, and 24th month, we detected the sputum hBD-2 level and levels of cytokines, such as CXCL10, CXCL11, and IFN. RESULTS: At baseline, there were no significant differences in the sputum and serum hBD-2 levels between the patients and the controls. However, the sputum hBD-2 levels of patients who had at least one symptom aggravation over the next 2 years were significantly lower than those of patients without any exacerbations (1130.9 ± 858.4 pg/mL vs. 2103.7 ± 1294.2 pg/mL, respectively; p = 0.001). Nevertheless, there were no statistically significant differences in the sputum hBD-2 levels between patients (no aggravation history) and controls (2084.9 ± 1317.6 pg/mL vs. 2152.5 ± 1251.6 pg/mL, respectively; p = 0.626). We used a logistic regression model to assess the relationship between aggravation and sputum hBD-2 levels. Interestingly, we found that low hBD-2 level (< 1000 pg/mL) was significantly associated with exacerbations. Specifically, patients with low hBD-2 levels were more likely to experience exacerbations in the next 12 months (0.333 vs. 0.117; p = 0.001). Moreover, we compared the hBD-2 levels between controls and patients with GOLD 3-4 and found that participants with bacteria (+) and/or viruses (+) had an association between hBD-2 level and disease severity (p = 0.02). CONCLUSION: Patients at risk of exacerbations are more likely to have lower sputum hBD-2 levels. These results have important implications for future therapies for COPD.

Phase Stability and Dual-Mode Photoluminescence Modulation in Er-Doped Lead Zirconate Titanate Antiferroelectrics.

The electric-field-modulation (E-modulation) of photoluminescence (PL) properties in bulk ceramics has attracted tremendous interest due to its potential application in optical data storage and communication devices. One promising approach of reversibly and largely modulating the PL intensity has been proposed in rare-earth Er3+-doped Pb0.96La0.04Zr0.9Ti0.1O3 (PLZT) antiferroelectrics (AFEs) based on the unique E-dependent antiferroelectric-ferroelectric (AFE-FE) phase transition. However, the AFE phase stability of PLZT doped with various Er contents and their E-modulated PL properties have not been systematically investigated. In this paper, the intrinsic AFE phase of PLZT-Er is found to be stabilized in the high-temperature and high-E regions with increasing Er3+ content. The enhanced AFE nature caused by increasing Er doping leads to a larger E-dependent PL tunability (∼35%). Moreover, the ceramics exhibit the characteristics of both upconversion and downconversion PL (UCPL and DCPL) effects. Based on the excellent E-dependent dual-mode PL tunability, an optoelectronic device named the optical latch is demonstrated, where an electric signal can be used to trigger a notable intensity change in both the UCPL and DCPL modes. This reversible E-dependent dual-mode capability in PLZT-Er sheds light on a feasible approach to optoelectronic applications.

Clinical characteristics of protracted bacterial bronchitis in adults.

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

Estimating stomatal conductance of citrus under water stress based on multispectral imagery and machine learning methods.

Introduction: Canopy stomatal conductance (Sc) indicates the strength of photosynthesis and transpiration of plants. In addition, Sc is a physiological indicator that is widely employed to detect crop water stress. Unfortunately, existing methods for measuring canopy Sc are time-consuming, laborious, and poorly representative. Methods: To solve these problems, in this study, we combined multispectral vegetation index (VI) and texture features to predict the Sc values and used citrus trees in the fruit growth period as the research object. To achieve this, VI and texture feature data of the experimental area were obtained using a multispectral camera. The H (Hue), S (Saturation) and V (Value) segmentation algorithm and the determined threshold of VI were used to obtain the canopy area images, and the accuracy of the extraction results was evaluated. Subsequently, the gray level co-occurrence matrix (GLCM) was used to calculate the eight texture features of the image, and then the full subset filter was used to obtain the sensitive image texture features and VI. Support vector regression, random forest regression, and k-nearest neighbor regression (KNR) Sc prediction models were constructed, which were based on single and combined variables. Results: The analysis revealed the following: 1) the accuracy of the HSV segmentation algorithm was the highest, achieving more than 80%. The accuracy of the VI threshold algorithm using excess green was approximately 80%, which achieved accurate segmentation. 2) The citrus tree photosynthetic parameters were all affected by different water supply treatments. The greater the degree of water stress, the lower the net photosynthetic rate (Pn), transpiration rate (Tr), and Sc of the leaves. 3) In the three Sc prediction models, The KNR model, which was constructed by combining image texture features and VI had the optimum prediction effect (training set: R2 = 0.91076, RMSE = 0.00070; validation set; R2 = 0.77937, RMSE = 0.00165). Compared with the KNR model, which was only based on VI or image texture features, the R2 of the validation set of the KNR model based on combined variables was improved respectively by 6.97% and 28.42%. Discussion: This study provides a reference for large-scale remote sensing monitoring of citrus Sc by multispectral technology. Moreover, it can be used to monitor the dynamic changes of Sc and provide a new technique for gaining a better understanding of the growth status and water stress of citrus crops.

Eosinophilia attention, diagnosis, treatment, and awareness in physicians: a cross-sectional survey.

Background: Patients with incidental eosinophilia is becoming increasingly common in clinical practice. But it remains challenging to diagnose and treat owing to its complex etiology. The awareness of physicians and the strategies of diagnosis and treatment toward eosinophilia are still unclear. Objective: We aimed to evaluate attention, diagnosis, treatment, and awareness of eosinophilia among physicians, as well as factors influencing clinical practice, and to find ways to improve the efficacy of this disease. Design: This is a cross-sectional survey. Methods: A cross-sectional study was conducted from 1 to 4 June 2021 in a tertiary hospital. Self-administered and validated electronic questionnaire was used to investigate the attention toward eosinophilia, the strategies of diagnosis and treatment, and the awareness in physicians. Results: A total of 607 valid questionnaires were collected, with a response rate of 84.5%. Among the responders, 65.4% of physicians claimed to be familiar with patients with eosinophilia but only 11.0% of them had read the relevant guidelines or expert consensus. Among 207 physicians who had ever diagnosed patients with eosinophilia, only 19.4% had performed detailed examinations. The accuracy of awareness questions was 1.6-53.5%, and only 26.5% of physicians had high levels of awareness. An increase in the awareness level of up to 2.82 folds was seen among physicians with factors such as job title, encountering patients with eosinophilia, linking patients' conditions to peripheral blood eosinophil count, and paying attention to guidelines. Conclusion: This study highlighted the importance of raising awareness and knowledge of eosinophilia among physicians in China. More works on education about eosinophilia guideline are needed, which may help physicians make decision with more benefits to patients.

Identification of Parameters Representative of Immune Dysfunction in Patients with Severe and Fatal COVID-19 Infection: a Systematic Review and Meta-analysis.

Abnormal immunological indicators associated with disease severity and mortality in patients with COVID-19 have been reported in several observational studies. However, there are marked heterogeneities in patient characteristics and research methodologies in these studies. We aimed to provide an updated synthesis of the association between immune-related indicators and COVID-19 prognosis. We conducted an electronic search of PubMed, Scopus, Ovid, Willey, Web of Science, Cochrane library, and CNKI for studies reporting immunological and/or immune-related parameters, including hematological, inflammatory, coagulation, and biochemical variables, tested on hospital admission of COVID-19 patients with different severities and outcomes. A total of 145 studies were included in the current meta-analysis, with 26 immunological, 11 hematological, 5 inflammatory, 4 coagulation, and 10 biochemical variables reported. Of them, levels of cytokines, including IL-1ß, IL-1Ra, IL-2R, IL-4, IL-6, IL-8, IL-10, IL-18, TNF-α, IFN-γ, IgA, IgG, and CD4+ T/CD8+ T cell ratio, WBC, neutrophil, platelet, ESR, CRP, ferritin, SAA, D-dimer, FIB, and LDH were significantly increased in severely ill patients or non-survivors. Moreover, non-severely ill patients or survivors presented significantly higher counts of lymphocytes, monocytes, lymphocyte/monocyte ratio, eosinophils, CD3+ T,CD4+T and CD8+T cells, B cells, and NK cells. The currently updated meta-analysis primarily identified a hypercytokinemia profile with the severity and mortality of COVID-19 containing IL-1ß, IL-1Ra, IL-2R, IL-4, IL-6, IL-8, IL-10, IL-18, TNF-α, and IFN-γ. Impaired innate and adaptive immune responses, reflected by decreased eosinophils, lymphocytes, monocytes, B cells, NK cells, T cells, and their subtype CD4+ and CD8+ T cells, and augmented inflammation, coagulation dysfunction, and nonpulmonary organ injury, were marked features of patients with poor prognosis. Therefore, parameters of immune response dysfunction combined with inflammatory, coagulated, or nonpulmonary organ injury indicators may be more sensitive to predict severe patients and those non-survivors.

Clinical characteristics in adult patients with somatic cough syndrome.

OBJECTIVE: The data in regard of the clinical characteristics and diagnosis of somatic cough syndrome in adults were limited. The aim of this study was to fill that gap. METHODS: This was a retrospective analysis of patients with somatic cough syndrome. We described clinical characteristics of adult patients with somatic cough syndrome. RESULTS: Twenty-three somatic cough syndrome patients were identified in 543 adult patients with chronic cough. Psychiatric disorder of these patients was identified as anxiety (n = 8), obsessive-compulsive (n = 7), somatoform (n = 6), depression (n = 3), and cognitive bias (n = 1). Twelve patients showed abnormal results of investigations related with common causes of chronic cough, including gastroesophageal reflux, sputum eosinophilia, bronchial hyper-responsiveness, or signs of sinusitis but did not respond to the treatments directed to those conditions. All these patients were ever misdiagnosed as other causes of chronic cough. Compared to 520 non-somatic cough syndrome patients, patients with somatic cough syndrome were younger (32 (29.0-43.0) vs 42.0 (32.0-55.0) years, p = 0.013), longer disease duration (48.0 (19.5-102.0) vs 24.0 (9.0-72.0) months, p = 0.037), more common in dry cough (100% vs 57.6%, p < 0.001), and lower proportion of nocturnal cough (13.0% vs 40.2%, p = 0.009). Common cold (60.9%) was the most common initial trigger of cough and itchy throat (60.9%) was the most common accompanying symptom in patients with somatic cough syndrome. Notably, there were similar distribution in cough triggers and accompanying symptoms between two groups. CONCLUSION: In spite of much higher proportion of dry cough and smaller proportion of nocturnal cough, adult patients with somatic cough syndrome show similar clinical characteristics with other chronic cough patients, in regard of cough triggers, accompanying symptoms as well as abnormal results of investigations, which should be an important reason for misdiagnosis of somatic cough syndrome. Psychiatric disorder should be addressed in clinical management of chronic cough.

Eosinophilia and Lung Cancer: Analysis From Real-World Data and Mendelian Randomization Study.

Background and Objective: Growing evidence added to the results from observational studies of lung cancer patients exhibiting eosinophilia. However, whether eosinophils contributed to tumor immune surveillance or neoplastic evolution was unknown. This study aimed to analyze the causal association between eosinophilia and lung cancer. Methods: The causal effect of eosinophil count on lung cancer from a genome-wide association study (GWAS) was investigated using the two-sample Mendelian randomization (MR) method. Secondary results according to different histological subtypes of lung cancer were also implemented. Meanwhile, we compared the measured levels of blood eosinophil counts among different subtypes of lung cancer from real-world data. Results: The median absolute eosinophilic count (unit: 109/L) [median (min, max): Lung adenocarcinoma 0.7 (0.5, 15); Squamous cell lung cancer 0.7 (0.5, 1.3); Small cell lung cancer 0.7 (0.6, 1.3); p = 0.96] and the median eosinophil to leukocyte ratio [median (min, max): Lung adenocarcinoma 8.7% (2.1, 42.2%); Squamous cell lung cancer 9.3% (4.1, 17.7%); Small cell lung cancer 8.9% (5.1, 24.1%); p = 0.91] were similar among different histological subtypes of lung cancer. MR methods indicated that eosinophilia may provide 28% higher risk for squamous cell lung cancer in East Asian [Weighted median method: odds ratio (OR) = 1.28, 95% CI: 1.04-1.57, p = 0.02]. Conclusion: Our study suggested that eosinophilia may be a potential causal risk factor in the progression of squamous cell lung cancer in East Asian.

Rigorous Assessment of Guidelines on COVID-19-Related Thrombotic or Thromboembolic Disease: Implications for Clinical Practice of Prevention, Diagnosis, and Treatment.

PURPOSE: Severe COVID-19 patients were prone to develop venous thromboembolism. Unfortunately, to date, there is no evidence of any effective medications for thromboembolism in COVID-19. The management of the disease relies on symptomatic and supportive treatments, giving rise to a variety of guidelines. However, the quality of methodology and clinical recommendations remains unknown. MATERIALS AND METHODS: We searched Medline, Cochrane Library, Web of Science, websites of international organizations and medical societies, and gray literature databases. Four well-trained appraisers independently evaluated the quality of eligible guidelines and extracted recommendations using well-recognized guideline appraisal tools. Furthermore, recommendations were extracted and reclassified according to a composite grading system. RESULTS: The search identified 23 guidelines that offered 108 recommendations. Guidelines scored average on AGREE II criteria, with Scope and Purpose and Clarity of Presentation highest. Only five (22%) guidelines provided high-quality recommendations. The existed clinical recommendations were inconsistent in terms of prophylaxis, diagnosis, and treatment of thromboembolic disease to some extent. CONCLUSION: Current guidelines for COVID-19 thromboembolism are generally of low quality, and clinical recommendations on thromboembolism are principally supported by insufficient evidence. There is still an urgent need for more well-designed clinical trials as evidence to prevent adverse events and improve prognosis during COVID-19 treatment.

Critical Review of the Scientific Evidence and Recommendations in COVID-19 Management Guidelines.

BACKGROUND: Little is known about the quality and potential impacts of the guidelines for coronavirus disease 2019 (COVID-19) management. METHODS: We systematically searched PubMed, Web of Science, Cochrane Library, guideline databases, and specialty society websites to evaluate the quality of the retrieved guidelines using the Appraisal of Guidelines for Research and Evaluation II. RESULTS: A total of 66 guidelines were identified. Only 24% were categorized as "recommended" for clinical practice. The 211 identified recommendations for COVID-19 management were classified into 4 topics: respiratory support (27), acute respiratory distress syndrome management (31), antiviral or immunomodulatory therapy (95), or other medicines (58). Only 63% and 56% of recommendations were supported by, respectively, assessment of the strength of the recommendations or level of evidence. There were notable discrepancies between the different guidelines regarding the recommendations on COVID-19 management. CONCLUSIONS: The quality of the guidelines for COVID-19 management is heterogeneous, and the recommendations are rarely supported by evidence.

Altered gut microbiome compositions are associated with the severity of asthma.

BACKGROUND: Despite substantial evidence on the contribution of the diversity of the gut microbiome to the pathogenesis of asthma and allergic diseases, little is known about their relationship with asthma severity and/or clinical phenotypes. We analyzed the difference in composition of the gut microbiome between subjects with asthma and healthy subjects and explored its role in the development of asthma. METHODS: Fecal samples from 15 subjects with severe asthma (SA), 14 with non-severe asthma (NSA), and 15 healthy subjects were assessed by 16S ribosomal RNA gene sequencing methods to identify the gut bacterial composition. RESULTS: Compared with those in the NSA group, patients in the SA group had a higher dose of inhaled corticosteroids, and there were more atopic subjects (60% vs. 35.7%, respectively). No significant differences were found at the phylum level either in operational taxonomic unit numbers or in diversity scores among the SA, NSA, and healthy groups. However, at the family level, the relative abundance of Acidaminococcaceae in the SA group was remarkedly lower than that in the group with healthy subjects (P<0.05). Furthermore, Veillonellaceae and Prevotellaceae were significantly more common in samples from the SA group than in those from the NSA group (P<0.05). In the SA group, positive correlations were observed between the relative abundance of Veillonellaceae and mid-expiratory flow 25% (MEF25%) predicted (r=0.538, P=0.047), as well as between the relative abundance of Acidaminococcaceae and body mass index (r=0642, P=0.010). Principal component analysis suggested that the relative abundances of Acidaminococcaceae and Prevotellaceae were associated with severe asthma. Moreover, we found that class Betaproteobacteria, order Burkholderiales, and family Alcaligenaceae were significantly different among the groups defined by serum immunoglobulin E (IgE) levels. CONCLUSIONS: Our findings suggest that altered gut microbiome compositions are involved in the severity of asthma and that there are specific bacteria related to different asthma phenotypes in terms of serum IgE levels.