[Annual progress on bronchial asthma diagnosis and treatment in 2023].

Bronchial asthma (referred to as asthma) is a common chronic inflammatory airway disease mediated by various immune cells, cytokines, and inflammatory mediators. This disease exhibits considerable heterogeneity in clinical symptoms, severity, and treatment outcomes, posing significant challenges to the diagnosis and treatment of asthma. This article reviews the literature on both basic and clinical research in asthma, published from October 1, 2022 to September 30, 2023. The review focuses on summarizing and elucidating four aspects of asthma: pathogenesis, diagnosis, assessment, and treatment. The aim is to provide more evidence for clinical diagnosis and treatment and offer new perspectives for future research.

[Epidemiology of asthma based on the standard questionnaire].

Asthma is a common chronic airway disease in the world. Although the guidelines recommend the diagnostic criteria for asthma, which have been widely used in clinical practice, the standardized asthma questionnaire is often recommended for prevalence surveys in large-scale epidemiological surveys of the population, because the standardized asthma questionnaire has the characteristics of good cost-effectiveness and high response rate, and the results are also feasible for comparison between different populations or regions. There are currently four asthma epidemiological surveys in the world, including the European Community Respiratory Health Survey (ECRHS), the International Study of Asthma and Allergies in Childhood (ISAAC), the International Study of Wheezing in Infants (EISL) and World Health Survey (WHS). The above research results were also important data source for estimating the global prevalence of asthma in the Global Burden of Disease Study (GBD). In China, several national surveys were conducted on the prevalence of asthma in children and adults, but the reported prevalence of asthma was not comparable with other countries because clinical diagnostic criteria for asthma were frequently used to define asthma in these previous studies. The China Pulmonary Health (CPH) study was a national cross-sectional study that enrolled a nationally representative sample of Chinese adults aged 20 years or older, using the asthma questionnaire derived from ECRHS, we reported that the prevalence of asthma with wheezing in Chinese adults was 4.2%, representing 45.7 million adult asthmatics. However, it should be realized that these data did not include people under the age of 20 years or those with atypical asthmatic symptoms. In addition, the study shows that asthma is largely under-diagnosed and undertreated in China, and these findings call for national efforts to improve the prevention, detection and treatment of asthma in China.

[Investigation on cognition, diagnosis and treatment status of chest tightness variant asthma among Chinese pediatricians].

Objective: To evaluate the awareness, diagnosis and treatment of chest tightness variant asthma (CTVA) among pediatricians in China. Methods: The survey was conducted by convenient sampling method. Pediatricians with professional title of attending physician and above from different grades hospitals in 30 provinces were invited to conduct online questionnaire surveys through WeChat, pediatricians scan QR codes to complete electronic questionnaires in the mini program from January 16th to February 4th, 2021. The contents of questionnaire included the awareness, diagnosis and treatment of CTVA, and comparing the differences between pediatricians in secondary hospitals and tertiary hospitals. Results: A total of 1 529 pediatricians participated in the survey, and 1 484 (97.06%) pediatricians completed the questionnaire and included in the analysis, including 420 males (28.30%). The awareness rate of CTVA among pediatricians was 77.83 % (1 155/1 484). Pediatricians in tertiary hospitals had higher rates of awareness of CTVA than pediatricians in secondary hospitals [81.86% (898/1 097) vs 66.41% (257/387), P<0.001] and had better execution of the guidelines [89.15% (978/1 097) vs 79.59% (308/387), P<0.001]. A total of 93.06 % (1 381/1 484) of pediatricians' first-line treatment included inhaled corticosteroids (ICS) for CTVA. Among them, a higher proportion of pediatricians in tertiary hospitals used ICS included regimens for first-line treatment of CTVA compared with pediatricians in secondary hospitals [94.90% (1 041/1 097) vs 87.86% (340/387), P<0.001]. The reported well control rate of CTVA was 32.08% (476/1 484), which was significantly lower in secondary hospitals than that in tertiary hospitals [17.31% (67/387) vs 37.28% (409/1 097), P<0.001]. Conclusion: Most pediatricians are well aware of CTVA, among which there is a certain gap in clinical practice between pediatricians in secondary hospitals and tertiary hospitals in terms of understanding, diagnosis, and treatment of CTVA.

[Complications of chronic cough].

Chronic cough is a common complaint, which may cause various complications involving many organ systems, including respiratory system, circulatory system, digestive system, urinary system, reproductive system, skeletal movement system, nervous system, etc. Cough and its complications are associated with an adverse impact on the work and quality of life in the huge population with chronic cough, and lead to an increased healthcare resource utilization. In this paper, we review the common complications of chronic cough by organ system classification.

Improved quantitative assessment of HBV-associated liver fibrosis using second-harmonic generation microscopy with feature selection.

BACKGROUND AND AIM: Quantitative assessments of liver fibrosis using second-harmonic generation/two-photon excited fluorescence microscopy provide greater sensitivity and accuracy than collagen proportionate area while eliminating operator-dependent variation in the staining process. In conjunction with sophisticated image analysis algorithms and feature selection, we might reduce the computation cost in future and narrow down the candidates for further clinical studies. METHODS: We sampled a total of 244 liver specimens from patients with hepatitis B viral infections who underwent liver biopsy or liver resection at the National Taiwan University Hospital. The samples were then imaged using a Genesis (HistoIndex Pte. Ltd, Singapore) system, wherein second-harmonic generation microscopy was used to visualize collagen, and two-photon excited fluorescence microscopy was used to visualize other cell structures. We used 100 morphological features extracted from the images to assess correlations with METAVIR fibrosis scores. RESULTS: Out of 100 quantitative measurements, 76 showed significant correlation with METAVIR scoring, thereby enabling the statistical discrimination of patients in various stages of the disease. These 76 features were also narrowed down by the nonlinear test to 10 candidate measurements, which can be further investigated in detail. CONCLUSIONS: Our experimental results showed that the model with 10 selected features can beat the one with second-harmonic generation only, and performed equivalently well compared the model with 76 features, especially for early-stage discrimination. Features presenting significant correlation were used to fit a single combined index in order to predict pathological staging, thereby making it possible to reveal incremental progress during treatment.

[Effect of particulate air pollution on hospital admissions for acute exacerbation of chronic obstructive pulmonary disease in Beijing].

OBJECTIVE: To assess the association between particulate air pollution and hospital admissions for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in Beijing, and to evaluate the differences of association among different subgroups. METHODS: Hospital admissions to intertiary hospitals for AECOPD from January 1, 2014, through December 31, 2015 were obtained from the electronic hospitalization summary reports (HSRs).We obtained the data on air pollution during the study period from the national air pollution monitoring system. The data on meteorological variables were obtained from the Chinese meteorological bureau. A poison generalized additive model was used to assess the effects of particulate pollution on AECOPD with adjustment for the long term trend, day of week, holiday effect and meteorological variables. Subgroup analyses were also conducted by age and gender, which would help identify higher-risk groups. RESULTS: A total of 7 884 hospitalizations from 15 tertiary hospitals were recorded during the study period, and 69.3% were male patients, 37.1% were ≥80 years of age, 45.5% were 65-79 years of age, and 17.4% were younger than 65. The mean (SD) daily concentrations of PM2.5, PM10 were 77.1 (66.6) µg/m3, 111.9 (75.8) µg/m3. Every 10 µg/m3 increase in particulate pollution concentration for a lag of 4 d was associated with an increase in hospital admissions for AECOPD as follows: 0.53% (95% CI: 0.01%-1.06%, P=0.0478) of PM2.5, 0.53% (95% CI: 0.07%-1.00%, P=0.0250) of PM10, respectively. We found differences in risk for AECOPD admissions among the different subgroups. For every 10 µg/m3 increase in PM2.5, PM10 exposure in the female group there was a 1.13% (95% CI: 0.19%-2.07%, P=0.018 3) increase, 1.06% (95% CI: 0.22%-1.91%, P=0.013 6) increase in admissions, respectively, while in the male group, the association was non-significant. The patients of 80 years of age and older demonstrated a higher risk of AECOPD, 1.25% (95% CI: 0.40%-2.11%, P=0.004 0) increase of PM2.5, 1.18% (95% CI: 0.42%-1.95%, P=0.002 4) increase of PM10, respectively, while other subgroups didn't find significant association. CONCLUSION: Our findings showed that particulate air pollution was significantly associated with hospital admissions for AECOPD in Beijing. The susceptibility to particulate pollution varied by gender and age.

Immunomagnetic Reduction Assay on Des-Gamma-Carboxy Prothrombin for Screening of Hepatocellular Carcinoma.

The accredited biomarker alpha-fetoprotein (AFP) offers limited sensitivity and specificity in the early detection of hepatocellular carcinoma (HCC). To improve the screening performance, des-gamma-carboxy prothrombin (DCP) has been identified as another promising biomarker of HCC, combined with AFP biomarkers. The results of the commercial optical enzyme-linked immunosorbent assay (ELISA) kit easily have the interference problem due to the optical methodology. The immunomagnetic reduction (IMR) assay based on the magnetic measurement was utilized to assay DCP biomarkers without the excellent antiinterference performances. A DCP magnetic reagent, composed of iron-oxide (Fe3O4 ) magnetic nanoparticles coated with anti-DCP antibodies solved in phosphoryl-buffer solution, was synthesized and characterized. In the test of standard DCP antigens, superior antiinterference and sensitivity than optical ELISA were proved. In the animal test, the results indicate good agreement between the IMR assay findings and the tumor sizes of HCC rats at all time points after the HCC implantation. The feasibility of the developed DCP magnetic reagent with the IMR for the detection of DCP is verified, and demonstrates the high potential for future clinical applications.

Initial institutional experience of uncooled single-antenna microwave ablation for large hepatocellular carcinoma.

AIM: To evaluate the safety, efficacy, and feasibility of a novel microwave generator, designed to deliver automatically adjusted energy by tissue permittivity feedback control into the tumour via an uncooled antenna, in patients with larger hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Fourteen patients with HCC >5 cm in diameter received surgical or percutaneous microwave ablation with more than 12 months of follow-up. Microwave ablation was performed using a 902-928 MHz generator at 28 W; a single 14 G antenna without water-cooled system was used. The patients were followed up with contrast-enhanced CT and serum alpha-foetoprotein to monitor for tumour recurrence at 1 month and then every 3 months after tumour ablation. RESULTS: The follow-up duration for the 11 male and three female patients (mean tumour size 5.77 cm, range 5-7 cm; mean age 63.8 years) was 15.8 months. The mean ablation time was 2025 s (range 900-3600 s), and the mean ablation session was 2.5 (range 1-4). The complete ablation rate was 85% (17 of 20). Local recurrence rate was 5.8% (1 of 17). All patients survived and the morbidity and mortality rate was 21.4% and 0%, respectively. CONCLUSIONS: Microwave tissue ablation using this novel system with tissue permittivity feedback control and a single uncooled antenna has a high complete ablation rate and lower morbidity. It proved to be a fast, easy, and effective option for ablation of large (>5 cm) tumours.

Direct comparison of the dynamics of IL-25- and 'allergen'-induced airways inflammation, remodelling and hypersensitivity in a murine asthma model.

BACKGROUND: Interleukin-25 has been implicated in the pathogenesis of asthma from studies on human asthmatics and in murine asthma models. OBJECTIVES: In this study, we hypothesized that chronic exposure of the airways to IL-25 alone is able to induce pathogenic changes observed in animal models of asthma. METHODS: We performed a detailed comparison of the dynamics of development of cellular infiltration, cytokine expression and airways remodelling and hyperresponsiveness in mice sensitized and challenged with OVA, a classical model of allergic asthma and those exposed to IL-25 alone. RESULTS: Intranasal challenge of BALB/c mice with IL-25 alone induced a delayed (compared with OVA-challenge), predominantly eosinophilic and lymphocytic infiltration into the airways lumen, along with increased production of Th2-type cytokines, chemokines and collagen, secretion of epithelial mucus, goblet cell hyperplasia, deposition of subepithelial collagen, airways smooth muscle cell hyperplasia and angiogenesis. Correspondingly, IL-25 as well as OVA challenge both induced airways hyperresponsiveness and increased lung tissue damping. In contrast, IL-25 exposure did not increase IgE or IgG1 production. CONCLUSIONS AND CLINICAL RELEVANCE: The data suggest that chronic airways exposure to IL-25 alone is sufficient to induce allergen- and IgE-independent, asthma-like airways inflammation, remodelling and hyperresponsiveness in mice. Thus, IL-25 is a key molecular target in asthma, irrespective of the coexistence of IgE-dependent mechanisms.

Patients with nonalcoholic fatty liver disease have higher risk of colorectal adenoma after negative baseline colonoscopy.

AIM: The study aimed to determine whether nonalcoholic fatty liver disease (NAFLD) is an independent risk factor of adenoma after negative baseline colonoscopy. METHOD: A retrospective cohort study was conducted on 1522 health-check individuals who underwent two consecutive colonoscopies at Taipei Veterans General Hospital between 2003 and 2010. Those developing an adenoma after an initial negative baseline colonoscopy (adenoma group) were compared with those in whom the second colonoscopy was negative (nonadenoma group). Anthropometric measurements, biochemical tests and the presence of NAFLD were compared between the two groups. RESULTS: The adenoma group had a higher prevalence of NAFLD than the nonadenoma group (55.6% vs 38.8%; P < 0.05). On multivariate logistic regression analysis, NAFLD was an independent risk factor (OR = 1.45, 95% CI: 1.07-1.98) for adenoma formation after a negative baseline colonoscopy. The risk of colorectal adenoma increased when NAFLD patients had other morbidities including metabolic syndrome, hypertension or smoking (OR = 2.85, 4.03 and 4.17). CONCLUSION: NAFLD is an independent risk factor for colorectal adenoma formation after a negative baseline colonoscopy. The risk is higher in individuals with NAFLD and other comorbidities, such as hypertension, smoking or metabolic syndrome.

Three dimensional microfluidics with embedded microball lenses for parallel and high throughput multicolor fluorescence detection.

We report a 3D microfluidic device with 32 detection channels and 64 sheath flow channels and embedded microball lens array for high throughput multicolor fluorescence detection. A throughput of 358 400 cells/s has been accomplished. This device is realized by utilizing solid immersion micro ball lens arrays for high sensitivity and parallel fluorescence detection. High refractive index micro ball lenses (n = 2.1) are embedded underneath PDMS channels close to cell detection zones in channels. This design permits patterning high N.A. micro ball lenses in a compact fashion for parallel fluorescence detection on a small footprint device. This device also utilizes 3D microfluidic fabrication to address fluid routing issues in two-dimensional parallel sheath focusing and allows simultaneous pumping of 32 sample channels and 64 sheath flow channels with only two inlets.

Interleukin-25 promotes basic fibroblast growth factor expression by human endothelial cells through interaction with IL-17RB, but not IL-17RA.

BACKGROUND: Unlike other IL-17 family members, the Th2-derived cytokine IL-25 (IL-17E) induces (promotes) Th2 responses. One or both of the two receptors for IL-25 (IL-17RA, IL-17RB) is expressed on inflammatory cells and tissue structural cells, suggesting that in addition to promoting Th2-type inflammation IL-25 may also act on structural cells at sites of Th2-type inflammation such as in the asthmatic bronchial mucosa to promote remodelling changes. OBJECTIVE: Our previous studies showed elevated expression of IL-25 and IL-17RB immunoreactivity in asthmatic airways with co-localization of the latter to endothelial cells. We therefore hypothesized that IL-25 acts on endothelial cells through this receptor to induce production of the key angiogenic and remodelling cytokine basic fibroblast growth factor (bFGF). METHODS: Polymerase chain reaction (PCR) immunocytochemistry/immunohistochemistry and ELISA were employed to detect expression of IL-17RB, IL-17RA and bFGF by human vascular endothelial cells (HUVEC) and immunoreactivity for IL-25 and bFGF in asthmatic bronchial biopsies. Receptor-blocking antibodies, PCR and an in vitro angiogenesis assay were used to investigate whether IL-25 acts on IL-17RB or IL-17RA to induce bFGF expression and angiogenesis. PCR was also employed to investigate the signalling pathways involved in IL-25-mediated bFGF expression. RESULTS: HUVEC constitutively expressed IL-17RB, IL-17RA and bFGF. Production of the latter was further increased by IL-25, but attenuated after blockade of the IL-17RB, but not the IL-17RA receptor. Neutralization of endogenous VEGF and bFGF completely abrogated IL-25-induced angiogenesis which was also inhibited by blocking IL-17RB, but not IL-17RA. The PI3K-specific inhibitor LY294002 also completely attenuated IL-25-induced bFGF expression. Immunoreactivity for IL-25 and bFGF was elevated in the asthmatic bronchial mucosa and the expression of each correlated with the other. CONCLUSIONS AND CLINICAL RELEVANCE: Our data support the hypothesis that IL-25 contributes to elevated bFGF in asthmatic airways by acting on the endothelial cell IL-17RB receptor through PI3K-signalling pathways. Targeting the pathways might benefit therapy of airways remodelling.

Chronic obstructive pulmonary disease: an independent risk factor for peptic ulcer bleeding: a nationwide population-based study.

BACKGROUND: Peptic ulcer bleeding remains a major healthcare problem despite decreasing prevalence of peptic ulcer disease. The role of chronic obstructive pulmonary disease (COPD) in the risk of peptic ulcer bleeding has not yet been established. AIM: To determine if COPD patients have a higher risk of peptic ulcer bleeding than the general population and to identify the risk factors of peptic ulcer bleeding in COPD patients. METHODS: From Taiwan's National Health Insurance research database, 62,876 patients, including 32,682 COPD and 30,194 age-gender-matched non-COPD controls, were recruited. Cox proportional hazard regression was performed to evaluate independent risk factors for ulcer bleeding in all patients and to identify risk factors in COPD patients. RESULTS: During the 8-year follow-up, COPD patients had a significant higher rate of peptic ulcer bleeding than the control group (P < 0.001, by log-rank test). By Cox proportional hazard regression analysis, COPD [hazard ratio (HR) 1.93, 95% CI 1.73-2.17] was an independent risk factor after adjusting for age, gender, underlying comorbidities and ulcerogenic medication. Age > 65 years, male, comorbidities of hypertension, diabetes, heart failure, history of peptic ulcer disease, and chronic renal disease and use of nonsteroidal anti-inflammatory drugs were risk factors of ulcer bleeding in COPD patients. CONCLUSION: Patients with chronic obstructive pulmonary disease have a higher risk of peptic ulcer bleeding after adjustments for possible confounding factors like underlying comorbidities and ulcerogenic medication.

Exploration of the relationship between the tumor burden and the concentration of vascular endothelial growth factor in liver-cancer-bearing animals using immunomagnetic reduction assay.

To achieve early-stage diagnosis, a high-sensitivity assay method is needed. As a biomarker, vascular endothelial growth factor (VEGF) has played a growing role in diagnosing and treating hepatocellular carcinoma (HCC). In this work, an immunomagnetic reduction (IMR) through bio-functionalized magnetic nanoparticles and a high-temperature superconducting-quantum-interference-device magnetometer were utilized for quantitative detection of low-concentration VEGF in serum from rats with HCC. The precision and accuracy of IMR on VEGF were characterized. Further, the results of assaying VEGF in the serum of rats were compared with those of using enzyme-linked immunosorbant assay (ELISA). It was found the correlations between the detected VEGF concentration in the rat serum and tumor burdens were 0.99 and 0.90 for IMR and ELISA, respectively, within the range from 2 pg/ml to 8000 pg/ml of VEGF concentration.

Randomised clinical trial: rabeprazole plus aspirin is not inferior to rabeprazole plus clopidogrel for the healing of aspirin-related peptic ulcer.

BACKGROUND: Clopidogrel does not inhibit prostaglandin synthesis. As a result, clopidogrel's incidence of peptic ulcer disease (PUD) and ulcer bleeding is lower than aspirin's. AIM: To compare the healing rate in aspirin-related dyspeptic ulcer patients who were given proton pump inhibitor (PPI) plus aspirin or PPI plus clopidogrel. METHODS: Patients with aspirin-related nonbleeding symptomatic ulcers were randomised to receive rabeprazole (20 mg/day) plus aspirin (100 mg/day) or rabeprazole (20 mg/day) plus clopidogrel (75 mg/day) for 12 weeks. The primary endpoint was the successful treatment of PUD as characterised by intention-to-treat at the end of therapy. RESULTS: Two hundred and eighteen patients (109 in the aspirin group and 109 in the clopidogrel group) were enrolled. There were no statistical demographic differences between the group that received aspirin and the group that received clopidogrel. The PUD treatment success rate was also statistically equal between the clopidogrel and aspirin groups (86.2% vs. 90.0%, P = 0.531). Neither group experienced ulcer-related bleeding. Multivariate logistic regression analysis showed that large ulcer size (>10 mm) (OR: 6.29, 95% CI: 2.58-15.37) and past history of PUD (OR: 3.69, 95% CI: 1.24-10.97) were important predictors of unsuccessful therapy for aspirin-related PUD. CONCLUSIONS: Rabeprazole plus aspirin is not inferior to rabeprazole plus clopidogrel in treating aspirin-related symptomatic PUD. Large ulcer size (>10 mm) and past history of PUD are important predictors of unsuccessful therapy (NCT 01037491).

Hepatic encephalopathy and cerebral blood flow improved by liver dialysis treatment.

Eight acute liver failure patients, all in grade IV hepatic encephalopathy, were administered liver dialysis treatment with the Hemo Therapies Unit (Hemo Therapies Inc, San Diego, CA, USA). The patients were evaluated to determine whether the Glasgow Coma Scale score and cerebral blood flow improved with treatment. After the initial treatment, consciousness levels as measured by the Glasgow Coma Scale improved from a pre-treatment median of 5 (range 3 to 6) to a post-treatment median of 7 (range 5 to 9) (p=0.0005 by paired Wilcoxon test); mean blood flow velocity in the middle cerebral arteries as shown by transcranial Doppler sonography increased from a median of 37.85 cm/sec (range 20.3 to 114.0) to 57.90 (32.5 to 135.0) post-treatment (p=0.022); however, there was no significant change in the pulsatility index from a median of 1.18 (range 0.61 to 1.71) to 0.85 (range 0.70 to approximately 1.79) post-treatment (p=0.13). The 8 patients received 2 to 7 (median 5.5) times of daily 6-h liver dialysis treatments. Following the completion of all liver dialysis treatments, hepatic coma was fully resolved in 4 of 8 patients (50%) Three of 8 patients (37.5%) survived to hospital discharge, whereas 5 patients did not survive due to irreversible liver function and associated complications. In conclusion, liver dialysis treatment could improve hepatic encephalopathy, but the prognosis still depended on the underlying diseases.

Selective sparing of human nucleus accumbens in aging and anoxia.

OBJECTIVE: To investigate the effects of aging and anoxia on the nucleus accumbens. METHODS: The number of neurons in nucleus accumbens and caudate nucleus in 35 patients over 65 and 35 under 65 years, all without neurological or psychiatric disease were counted. RESULTS: There was no statistically significant difference between the number of neurons in the accumbens in the two groups, but there was a decrease in the number of neurons in the elderly group. There was no reduction in volume of the neuronal nucleoli of the accumbens measured in 12 elderly patients compared to controls. These data suggest a sparing of the accumbens from changes associated with aging. There was relative preservation of the nucleus accumbens in 3 patients with anoxic encephalopathy. CONCLUSIONS: These results show that accumbens was resistant to both aging and anoxia, the mechanism of which is discussed.

Experimental study of NADPH-diaphorase positive neurons in nucleus accumbens of rats.

BACKGROUND: In order to explain the mechanism for the sparing of the nucleus accumbens in several pathologic conditions, the accumbens, caudate and putamen were examined in an experimental model. METHODS: The neurons in these regions from twenty adult rats were stained for the enzyme nicotinamide adenine dinucleotide phosphate (NADPH-diaphorase) and quantified. RESULTS: Positive neurons in the nucleus accumbens were more abundant than in the caudate and putamen. CONCLUSIONS: Since these neurons have been shown to be resistant to ischemia and degeneration, it is suggested that the mechanism for the sparing of the nucleus accumbens is related to the presence of a large number of NADPH-diaphorase positive neurons.