The prevalence and clinical features of chronic obstructive pulmonary disease patients with traits of asthma in Taiwan.

BACKGROUND/PURPOSE: The application of the checkbox for identifying patients with traits of both chronic obstructive pulmonary disease (COPD) and asthma proposed by the 2015 Global Initiative for Asthma (GINA)/Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommendations has not been well studied although such identification is important in clinical practice. Thus, we aimed to investigate the prevalence and features of COPD coexistent with asthma traits diagnosed based on the 2015 GINA/GOLD strategies, and explore the gap between guidelines and routine practice in the diagnosis and pharmacological management of such condition in a COPD cohort. METHODS: COPD subjects were enrolled retrospectively throughout Taiwan. A patient record form was completed for each participant and the data were analyzed. RESULTS: Of 340 participants, the prevalence of COPD coexistent with traits of asthma was 39.4% and 30.3% based on guidelines and physician's judgment, respectively. Coexistent patients were characterized by blood eosinophilia, higher total immunoglobulin E (IgE) levels, preserved lung function, and the presence of gastro-esophageal reflux disease and atopic disease while total IgE level > 100 kU/L and the presence of atopic disease were predictors for coexistent patients. Gaps existed in the diagnosis (a weak agreement with kappa = 0.53) and treatment (non-adherence to the preferred therapy in 18.4% of physician-judged coexistent patients) in COPD patients with asthma traits. The exacerbation history was similar between coexistent and non-coexistent patients. CONCLUSION: We found that measuring circulatory eosinophil and total IgE levels may raise clinicians' awareness of the presence of traits of asthma in the management of COPD.

Is PM2.5 associated with emergency department visits for mechanical ventilation in acute exacerbation of chronic obstructive pulmonary disease?

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) can have recurrent exacerbations and acute respiratory failure (ARF) triggered by particulate matter with a diameter of ≤2.5 µm (PM2.5). To prevent ventilator shortages, this study investigated the short-term association between PM2.5 concentration and emergency department visits (EDVs) among patients with acute exacerbation of COPD (AECOPD) requiring mechanical ventilation (MV). METHODS: We conducted a time-series study to predict the PM2.5 concentration and number of ventilators needed. Daily counts of EDVs among AECOPD patients requiring ventilation from 2015 to 2019 were obtained from a hospital. Generalized linear models extending Poisson regression were used to explore the association of AECOPD with PM2.5 after controlling for the time trend, seasonal variations, and meteorological variables. RESULTS: Eight hundred seventy-five AECOPD patients receiving MV were recorded, of whom 734 received noninvasive ventilation and 141 received invasive ventilatory support. EDVs for AECOPD patients with ARF significantly increased by 3.5% (95% confidence interval [CI]: 2.51%-4.42%) per 10 µg m-3 increase in PM2.5 concentration. Among seasons, PM2.5 concentration had the strongest effect on AECOPD patients with ARF in spring (<24.5 °C), with a 1.64% (95% CI: -0.56% to 3.83%) increase in admissions per 10 µg m-3 increase in same-day PM2.5 concentration. The interquartile range increase of 20 µg m-3 between winter and spring was associated with an average EDV increase of 48.66%. CONCLUSION: This is the first study to predict the number of ventilators required by calculating quantitative estimates of the short-term effects of PM2.5 on EDVs for AECOPD patients with ARF. Adverse effects of PM2.5 on AECOPD patients requiring MV are evident, especially in the spring. Establishing protective standards and reducing the PM2.5 concentration to below various thresholds are urgently needed.

Update on guidelines for the treatment of COPD in Taiwan using evidence and GRADE system-based recommendations.

Chronic obstructive pulmonary disease (COPD) has significant contributions to morbidity and mortality world-wide. Early symptoms of COPD are not readily distinguishable, resulting in a low rate of diagnosis and intervention. Different guidelines and recommendatations for the diagnosis and treatment of COPD exist globally. The first edition of clinical practice guidelines for COPD was published in 2016 by the Ministry of Health and Welfare in Taiwan in collaboration with the Taiwan evidence-based medicine association and Cochrane Taiwan, and was revised in 2019 in order to update recent diagnostic and therapeutic modalities for COPD and its acute exacerbation. This revised guideline covered a range of topics highlighted in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) report, including strategies for the diagnosis, assessment, monitoring, and management of stable COPD and exacerbations, with particular focus on evidence from Taiwan. The recommendations included in the revised guideline were formed based on a comprehensive systematic review or meta-analysis of specific clinical issues identified by an expert panel that surveyed relevant scientific evidence in the literature and guidelines published by the clinical communities and organizations nationally and internationally. The guidelines and recommendations are applicable to the clinical settings in Taiwan. We expect this revised guideline to facilitate the diagnosis, treatment and management of patients with COPD by physicians and health care professionals in Taiwan. Adaptations of the materials included herein for educational and training purposes is encouraged.

The impact on incident tuberculosis by kidney function impairment status: analysis of severity relationship.

BACKGROUND: The risk of tuberculosis (TB) in patients with impaired kidney function remains unclear by different stages of renal function impairment. METHODS: We retrospectively recruited all patients with kidney function in a tertiary-care referral center from January 2008 to December 2013 and followed them till December 2016. We defined the primary outcome as active TB development and analyzed the impact of kidney function impairment. RESULTS: During the study period, a total of 289,579 patients were enrolled for analysis, and of them, 1012 patients had active TB events in an average of 4.13 years of follow-up. According to kidney function impairment, the incidence rate of TB was similar in patients with no chronic kidney disease (CKD) or stage 1 and stage 2, and it increased apparently at stage 3a (167.68 per 100,000 person-years) to stage 3b, stage 4 and stage 5 (229.25, 304.95 and 349.29 per 100,000 person-years, respectively). In a Cox proportional hazard regression model, the dose response of TB risk among different stages of kidney function impairment increased significantly from CKD stage 3a to stage 5. Patients with long-term dialysis had a hazard ratio of 2.041 (1.092-3.815, p = 0.0254), which is similar to that of stage 4 CKD but lower than that of stage 5. CONCLUSION: In patients with impaired kidney function, the risk of TB increases from CKD stage 3, and in stage 5, the risk is even higher than that of those receiving dialysis. Further strategies of TB control need to consider this high-risk group.

Mono- and poly-functional T cells in nontuberculous mycobacteria lung disease patients: Implications in analyzing risk of disease progression.

AT A GLANCE: The diagnosis and progression of nontuberculous mycobacteria lung disease (NTN-LD) are important for clinical judgement but cannot easily be predicted. The immunological response of mono- and poly-functional T cells, a representative of host reactivity to NTM, could be a surrogate biomarker for disease and progression prediction. BACKGROUND: Mycobacterium avium complex (MAC) and M. abscessus (MAB) induced lung disease (LD) have become a clinical concern. Predicting clinical disease relevance and progression is important, but suitable biomarkers are lacking. The host immune response of mono- and poly-functional T cells might aid in clinical judgement. METHODS: We enrolled 140 participants, including 42 MAC-LD, 25 MAB-LD, 31 MAC airway colonization (MAC-Co), 15 MAB-Co patients, and 27 healthy controls. Their blood mono- and poly-functional T cells were measured and analyzed after in-vitro stimulation. RESULTS: Patients with MAC-LD generally had lower total IFN-γ+, total TNF-α+ and triple-positive T cells but higher mono-IL-2+ expression than the controls and MAC-Co group. The MAB-LD group had lower total IL-2 and triple positive cells than the controls and colonization group. Multivariate analysis revealed that body mass index (BMI), mono-IL2+ CD4+ and triple positive-CD8+ cells (PMA stimulation) significantly predicted MAC-LD from the controls. By contrast, male gender and triple positive-CD4+ cells predicted MAC-LD from colonization. On the other hand, the triple positive-CD4+ cells (PMA stimulation) alone or together with the mock/MAB ratio of IL-2+/TNF-α+ CD4 cells could predict MAB-LD in the MAB-Co group or the controls. Among MAC/MAB-LD patients without anti-mycobacterial treatment, MAC-specific mono-IFN-γ+ CD4+ cells and PMA-induced triple positive-CD4+ cells were correlated with progression, with an area under the ROC curve of 0.875. CONCLUSIONS: The patients with MAC/MAB-LD had attenuated poly-functional T cells. The triple-positive CD4+ cells could be useful in diagnosing disease from colonization. MAC-specific mono-IFN-γ+ CD4+ cells and triple positive-CD4+ might predict radiographic progression, which could be useful in making treatment decisions.

Large-scale production and directed induction of functional dendritic cells ex vivo from serum-free expanded human hematopoietic stem cells.

BACKGROUND: Dendritic cells (DCs) that are derived from hematopoietic stem cells (HSCs) are the most potent antigen-presenting cells and play a pivotal role in initiating the immune response. Hence, large-scale production and direct induction of functional DCs ex vivo from HSCs are crucial to HSC research and clinical potential, such as vaccines for cancer and immune therapy. METHODS: In a previous study, we developed a serum-free HSC expansion system (SF-HSC medium) to expand large numbers of primitive HSCs ex vivo. Herein, a DC induction and expansion medium (DC medium) was proposed to further generate large numbers of functional DCs from serum-free expanded HSCs, which were developed and optimized by factorial design and the steepest ascent method. RESULTS: The DC medium is composed of effective basal medium (Iscove's modified Dulbecco's medium [IMDM]) and cytokines (2.9 ng/mL stem cell factor [SCF], 2.1 ng/mL Flt-3 ligand, 3.6 ng/mL interleukin [IL]-1ß, 19.3 ng/mL granulocyte-macrophage colony-stimulating factor [GM-CSF] and 20.0 ng/mL tumor necrosis factor-α [TNF-α]). After 10-day culture in DC medium, the maximum fold expansion for accumulated CD1a+CD11c+ DCs was more than 4000-fold, and the induced DCs were characterized and confirmed by analysis of growth kinetics, surface antigen expression, endocytosis ability, mixed lymphocyte reaction, specific cytokine secretion and lipopolysaccharide stimulation. DISCUSSION: In conclusion, the combination of DC medium and SF-HSC medium can efficiently induce and expand a large amount of functional DCs from a small scale of HSCs and might be a promising source of DCs for vaccine and immune therapy in the near future.

Comparison between COPD Assessment Test (CAT) and modified Medical Research Council (mMRC) dyspnea scores for evaluation of clinical symptoms, comorbidities and medical resources utilization in COPD patients.

BACKGROUND: The 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD) proposed a new severity assessment system for emphasizing clinical symptom evaluation by COPD Assessment Test (CAT) or modified Medical Research Council (mMRC) dyspnea scores. The aim of the study was to evaluate the effectiveness of two scoring systems in evaluating COPD patients. METHODS: A population based cross-sectional study employing computer-assisted telephone interviewing system (CATI) for surveying the epidemiology of COPD in Taiwan. Among 6600 subjects recruited (age > 40), 404 subjects (6.1%) were diagnosed as COPD. The comorbidities, COPD-related symptoms, health care resources utilization were compared between CAT and mMRC. RESULTS: There were significant differences in all co-morbidities, symptom severity in favor of CAT as compared to mMRC. When comparing health care resources utilization, CAT and mMRC have equal effectiveness in evaluating patients with regular medical treatment. There were significant differences in emergency room visit and hospitalization in favor of mMRC. However, CAT was more effective in evaluating patients with ICU admission (P = 0.005). CONCLUSION: Compared with CAT and mMRC, there are individual benefits in the evaluation of clinical symptoms, co-morbidities and medical resources utilization for ER, hospitalization and ICU admission in COPD patients.

MMP-12 activates protease-activated receptor-1, upregulates placenta growth factor, and leads to pulmonary emphysema.

Because of the expansion of aging and smoking populations, chronic obstructive pulmonary disease (COPD) is predicted to be the third leading cause of death worldwide in 2030. Therefore, it is pertinent to develop effective therapy to improve management for COPD. Cigarette smoke-mediated protease-antiprotease imbalance is a major pathogenic mechanism for COPD and results in massive pulmonary infiltration of neutrophils and macrophages, releasing excessive neutrophil elastase (NE) and matrix metalloproteinases (MMPs). Our previous studies indicated that placenta growth factor (PGF) and PGF-triggered downstream signaling molecules mediate NE-induced lung epithelial cell apoptosis, which is a major pathogenic mechanism for pulmonary emphysema. However, the relationship between MMP-directed COPD and PGF remains elusive. We hypothesize that MMPs may upregulate PGF expression and be involved in MMP-mediated pathogenesis of COPD. In this study, we demonstrate that only MMP-12 can increase the expression of PGF by increasing early-growth response protein 1 (Egr-1) level through the activation of protease-activated receptor 1 (PAR-1). The PGF-mediated downstream signaling molecules drive caspase-3 and caspase-9-dependent apoptosis in bronchial epithelial cells. Both the upregulation of PGF by MMP-12 and PGF downstream signaling molecules with pulmonary apoptosis and emphysema were also demonstrated in animals. Given these findings, we suggest that both human COPD-associated elastases, NE, and MMP-12, upregulate PGF expression and promote the progression of emphysema and COPD.

Factors responsible for poor sleep quality in patients with chronic obstructive pulmonary disease.

BACKGROUND: Sleep disturbance is a common complaint in patients with chronic obstructive lung disease (COPD). However, the factors resulting in sleep disturbance remain unclear. This retrospective, observational, multicenter study aimed to identify the factors associated with sleep disturbance in patients with COPD. METHODS: The study was a retrospective, observational, and multicenter research. Data including age, sex, body mass index, smoking status, COPD inhaler prescribed, clinical symptoms, pulmonary function tests, medical history of comorbidities, and questionnaires were collected. Parameters including demographics, symptoms, medication, severity, functional classification, and comorbidities were correlated with sleep quality scores. RESULTS: Among 377 patients with COPD, 200 (53 %) patients experienced poor sleep quality (Pittsburg Sleep Quality Index scores > 5). A significant difference in sleep quality, as measured by PSQI scores, was noted between groups based on the 2011 Global Initiatives for Chronic Obstructive Lung Disease (GOLD) classification system. The most common sleep disturbances included "getting up to use the bathroom" (70.3 %), "wake up at night or early morning" (40.3 %), and "cough and snore loudly at night" (15.9 %). The use of inhaled corticosteroids, the presence of wheezing, COPD Assessment Test (CAT) scores, and Modified Medical Research Council (mMRC) dyspnea scale scores positively correlated with poor sleep quality (odds ratio: 1.51, 1.66, 1.09, and 1.30, respectively). Upon multivariate analysis, the CAT score was an independent factor for poor sleep quality in these patients. With the exception of sleep problem items, based on the CAT questionnaire, phlegm was significantly higher in COPD patients with poor sleep quality. CONCLUSIONS: Poor sleep quality is common among patients with COPD and symptoms including wheeze, phlegm, and inhaled corticosteroid use may contribute to poor sleep quality. The CAT score is a good indicator of poor sleep quality in patients with COPD.

Selection of empirical antibiotics for health care-associated pneumonia via integration of pneumonia severity index and risk factors of drug-resistant pathogens.

BACKGROUND/PURPOSE: The pneumonia severity index (PSI) both contains some risk factors of drug-resistant pathogens (DRPs) and represents the severity of health care-associated pneumonia. The aim of this study was to investigate whether the PSI could be used to predict DRPs and whether there were risk factors beyond the PSI. METHODS: A retrospective observational study enrolled 530 patients with health care-associated pneumonia who were admitted from January 2005 to December 2010 in a tertiary care hospital. RESULTS: A total of 206 patients (38.9%) had DRPs, of which the most common was Pseudomonas aeruginosa (24.3%). The incidence of DRPs increased with increasing PSI classes (6.7%, 25.5%, 36.9%, and 44.6% in PSI II, III, IV, and V, respectively). An analysis of the risk factors for DRPs by PSI classes revealed that wound care was associated with methicillin-resistant Staphylococcus aureus (MRSA) infection in PSI V (p = 0.045). Nasogastric tube feeding (odds ratio, 3.88; 95% confidence interval, 1.75-8.60; p = 0.006), and bronchiectasis (odds ratio, 3.12; 95% confidence interval, 0.66-14.69; p = 0.007) were risk factors for DRPs in PSI III and IV. The area under the receiver operating characteristic curve progressed from 0.578 to 0.651 while integrating these risk factors with PSI classes. CONCLUSION: The findings suggested that PSI plus risk factors predicted the risk of DRPs. PSI II had a low risk of DRPs and could be treated as community-acquired pneumonia. Antibiotics of PSI III and IV with risk factors could be targeted DRPs. PSI V with wound care had a higher risk of MRSA, and empirical anti-MRSA antibiotics could be added.

PlGF mediates neutrophil elastase-induced airway epithelial cell apoptosis and emphysema.

BACKGROUND: Chronic pulmonary obstructive disease (COPD) has become the fourth leading cause of death worldwide. Cigarette smoking induces neutrophil elastase (NE) and contributes to COPD, but the detailed mechanisms involved are not fully established. In an animal model of pulmonary emphysema, there are increased expressions of placenta growth factor (PlGF) and lung epithelial (LE) cell apoptosis. This study hypothesized that excessive NE may up-regulate PlGF and that PlGF-induced LE apoptosis mediates the pathogenesis of pulmonary emphysema. METHODS: Human bronchial epithelial cells, BEAS-2B, and primary mouse type II alveolar epithelial cells were treated with NE. The PlGF promoter activity was examined by luciferase activity assay, while PlGF expression and secretion were evaluated by RT-PCR, Western blotting, and ELISA. Both cell lines were treated with PlGF to evaluate its effects and the downstream signaling pathways leading to LE cell apoptosis. PlGF knockout and wild-type mice were instilled with NE to determine the roles of PlGF and its downstream molecules in NE-promoted mice pulmonary apoptosis and emphysema phenotype. RESULTS: The transcriptional factor, early growth response gene-1, was involved in the NE-promoted PlGF promoter activity, and the expression and secretion of PlGF mRNA and protein in LE cells. PlGF-induced LE cell apoptosis and NE-induced mice pulmonary apoptosis and emphysema were mediated by the downstream c-Jun N-terminal kinase (JNK) and protein kinase C (PKC)δ signaling pathways. CONCLUSION: The NE-PlGF-JNK/PKCδ pathway contributes to the pathogenesis of LE cell apoptosis and emphysema. PlGF and its downstream signaling molecules may be potential therapeutic targets for COPD.

The role of treatment regimen and duration in treating patients with Mycobacterium avium complex lung disease: A real-world experience and case-control study.

PURPOSE: The treatment advantage of guideline-based therapy (GBT) in Mycobacterium avium complex lung disease (MAC-LD) is well-known. However, GBT is not always feasible. The aim of the study was to analyze the relationship of treatment regimens and duration with outcomes. MATERIALS AND METHODS: This study screened patients with MAC-LD from Jan 2011 to Dec 2020 and enrolled those who received treatment. The treatment regimens were categorized to triple therapy (three active drugs) and non-triple therapy. The favorable outcomes included microbiological cure or clinical cure if no microbiologic persistence. RESULTS: A total of 106 patients with MAC-LD were enrolled. Among them, 88 subjects (83 %) received triple therapy, 58 (54.7 %) had MAC treatment >12 months, and 66 (62.3 %) had favorable outcomes. Patients receiving triple therapy (90.9 % vs. 67.5 %, p = 0.008) and treatment >12 months (62.1 % vs. 42.5 %, p = 0.07) had higher proportion of favorable outcomes than unfavorable outcomes. Multivariable logistic regression analysis showed that age >65, comorbidities of COPD and prior tuberculosis, low hemoglobin, and high MAC burden were independent risk factors of unfavorable outcome. In contrast, triple therapy (OR: 0.018, 95 % CI: 0.04-0.78, p = 0.022) and treatment duration >12 months (OR: 0.20, 95 % CI: 0.055-0.69, p = 0.012) were protective factors against unfavorable outcome. CONCLUSIONS: Triple therapy including GBT, and treatment more than 12 months achieved more favorable outcome. Maintenance of triple therapy, but not reducing the number of active drugs, might be an acceptable alternative of GBT.

Revisiting the association between vitamin D deficiency and active tuberculosis: A prospective case-control study in Taiwan.

BACKGROUND: To revisit the association between vitamin D deficiency (VDD, defined as serum 25(OH)D < 20 ng/ml) and incident active tuberculosis (TB), after two potentially underpowered randomized trials showed statistically non-significant 13%-22% decrease in TB incidence in vitamin D supplementation groups. METHODS: We prospectively conducted an age/sex-matched case-control study that accounting for body-mass index (BMI), smoking, and other confounding factors to examine the association between VDD and active TB among non-HIV people in Taiwan (latitude 24°N), a high-income society which continues to have moderate TB burden. RESULTS: We enrolled 62 people with incident active TB and 248 people in control group. The TB case patients had a significantly higher proportion of VDD compared to the control group (51.6% vs 29.8%, p = 0.001). The 25(OH)D level was also significantly lower in TB patients compared to control group (21.25 ± 8.93 ng/ml vs 24.45 ± 8.36 ng/ml, p = 0.008). In multivariable analysis, VDD (adjusted odds ratio [aOR]: 3.03, p = 0.002), lower BMI (aOR: 0.81, p < 0.001), liver cirrhosis (aOR: 8.99, p = 0.042), and smoking (aOR: 4.52, p = 0.001) were independent risk factors for incident active TB. CONCLUSIONS: VDD is an independent risk factor for incident active TB. Future randomized trials examining the effect of vitamin D supplementation on TB incidence should focus on people with a low BMI or other risk factors to maximize the statistical power.

Correlating Reiff scores with clinical, functional, and prognostic factors: characterizing noncystic fibrosis bronchiectasis severity: validation from a nationwide multicenter study in Taiwan.

BACKGROUND: Our study aimed to confirm a simplified radiological scoring system, derived from a modified Reiff score, to evaluate its relationship with clinical symptoms and predictive outcomes in Taiwanese patients with noncystic fibrosis bronchiectasis (NCFB). METHODS: This extensive multicenter retrospective study, performed in Taiwan, concentrated on patients diagnosed with NCFB verified through high-resolution computed tomography (HRCT) scans. We not only compared the clinical features of various types of bronchiectasis (cylindrical, varicose, and cystic). Furthermore, we established relationships between the severity of clinical factors, including symptom scores, pulmonary function, pseudomonas aeruginosa colonization, exacerbation and admission rates, and HRCT parameters using modified Reiff scores. RESULTS: Data from 2,753 patients were classified based on HRCT patterns (cylindrical, varicose, and cystic) and severity, assessed by modified Reiff scores (mild, moderate, and severe). With increasing HRCT severity, a significant correlation was found with decreased forced expiratory volume in the first second (FEV1) (p < 0.001), heightened clinical symptoms (p < 0.001), elevated pathogen colonization (pseudomonas aeruginosa) (p < 0.001), and an increased annual hospitalization rate (p < 0.001). In the following multivariate analysis, elderly age, pseudomonas aeruginosa pneumonia, and hospitalizations per year emerged as the only independent predictors of mortality. CONCLUSION: Based on our large cohort study, the simplified CT scoring system (Reiff score) can serve as a useful adjunct to clinical factors in predicting disease severity and prognosis among Taiwanese patients with NCFB.

Expression of Gα12 predicts progression and prognosis of oral squamous cell carcinomas in Taiwan.

BACKGROUND: Expression of Gα12 is found to be associated with cancer cell proliferation, migration, invasion, and metastasis. METHODS: This study used immunohistochemistry to examine the expression of Gα12 protein in 100 specimens of oral squamous cell carcinoma (OSCC), 45 specimens of oral epithelial dysplasia (OED), and 36 specimens of normal oral mucosa (NOM). RESULTS: The mean Gα12 labeling indices (LIs, defined as the percentage of positive cells in total cells) increased significantly from NOM (7 ± 11%) through OED (21 ± 20%) to OSCC samples (53 ± 33%, P < 0.001). The higher mean Gα12 LI was significantly associated with OSCCs with larger tumor size (P = 0.003), positive lymph node metastasis (P = 0.002), or more advanced clinical stages (P = 0.003). Positive lymph node metastasis (P = 0.039) and Gα12 LI > 50% (P = 0.009) were identified as independent unfavorable prognosis factors by multivariate analyses with Cox regression model. Moreover, Kaplan-Meier curve showed that OSCC patients with a Gα12 LI > 50% had a significantly poorer cumulative survival than those with a Gα12 LI ≤ 50% (log-rank test, P = 0.009). CONCLUSIONS: Our results showed a stepwise and significant elevation in Gα12 protein expression from NOM through OED to OSCCs, suggesting that overexpression of Gα12 protein may be an early event in oral carcinogenesis and may play a pivotal role in oral cancer development. Moreover, the Gα12 protein can be a biomarker for prediction of the progression of OSCCs and the prognosis of patients with OSCC in Taiwan.

Increased placenta growth factor mRNA level is significantly associated with progression, recurrence and poor prognosis of oral squamous cell carcinoma.

BACKGROUND/PURPOSE: Expression of placenta growth factor (PlGF) mRNA is shown to correlate with the progression and prognosis of several human cancers. In this study, we assessed whether the PlGF mRNA level in oral squamous cell carcinoma (OSCC) tissue could be used to predict the progression and prognosis of OSCCs in Taiwan. METHODS: This study used quantitative real-time reverse transcription-polymerase chain reaction (quantitative RT-PCR) to detect the PlGF mRNA levels in 63 paired OSCC and adjacent normal-looking oral mucosa (non-OSCC) tissues. Threshold cycle (CT) was defined as the PCR cycle number needed to generate a pre-determined amount of DNA (threshold). For a chosen threshold, a smaller starting copy number of mRNA results in a higher CT value. In this study, the relative expression level of tissue PlGF mRNA in each OSCC patients was expressed as -ΔCT = -(OSCC CT - non-OSCC CT). Thus, the higher the -ΔCT, the greater the copy number of PlGF mRNA in tissues. RESULTS: We found that the higher mean PlGF mRNA -ΔCT value was significantly associated with OSCCs with larger tumor size (p = 0.03), positive lymph node metastasis (p = 0.003), more advanced clinical stages (p = 0.013) or the presence of loco-regional recurrence (p = 0.039). Positive lymph node metastasis (p = 0.019) and PlGF mRNA -ΔCT value >2 (p = 0.016) were identified as two independent unfavorable prognosis factors by multivariate analyses with Cox regression model. Moreover, Kaplan-Meier curve showed that OSCC patients with a PlGF mRNA -ΔCT value >2 had a significantly poorer recurrence-free survival than those with a PlGF mRNA -ΔCT value ≤2 (log-rank test, p = 0.017). CONCLUSION: The OSCC tissue PlGF mRNA level can be used to predict the progression and prognosis of OSCCs in Taiwan.

Pathophysiology, Therapeutic Targets, and Future Therapeutic Alternatives in COPD: Focus on the Importance of the Cholinergic System.

Chronic obstructive pulmonary disease (COPD) is a progressive disease characterized by airway limitation and changes in airway structure. It has a high global burden of mortality and morbidity. The etiology of COPD is complex, but exposure to tobacco smoke and other inhaled lung oxidants are major risk factors. Both pharmacological and non-pharmacological approaches are used to manage COPD, but there remains an urgent unmet need for drugs that can modify the course of the disease. This review focuses on the role of acetylcholine and other components of the pulmonary cholinergic system in the pathogenesis of COPD, and the inhaled pharmacological agents that target it. In addition to its role as a neurotransmitter, acetylcholine regulates diverse aspects of COPD pathogenesis including bronchoconstriction, airway remodeling, mucus secretion and inflammation. Inhaled antimuscarinic drugs are a key component of therapy for COPD, as monotherapy or in combination with inhaled ß2 agonists or corticosteroids. We review the evidence supporting the use of current anticholinergic agents in COPD and preview novel drugs targeting the cholinergic system and agents from other classes in clinical development, such as phosphodiesterase-4 inhibitors and monoclonal antibodies targeting inflammatory mediators.

Current Progress of COPD Early Detection: Key Points and Novel Strategies.

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide, with approximately 70% to 80% of adults with COPD being undiagnosed. Patients with undiagnosed COPD are at increased risk of poor outcomes and a worsened quality of life, making early detection a crucial strategy to mitigate the impact of COPD and reduce the burden on healthcare systems. In the past decade, increased interest has been focused on the development of effective strategies and instrument for COPD early detection. However, identifying undiagnosed cases of COPD is still challenging. Both screening and case-finding approaches have been adopted to identify undiagnosed COPD, with case-finding being recommended by the 2023 Global Initiative for Chronic Obstructive Lung Disease (GOLD) guideline and the updated United States Preventive Services Task Force (USPTF) recommendation. Nonetheless, the approaches, criteria, and instruments used for early detection of COPD are varied. However, advances in the taxonomy and risk factors of COPD are continuously being investigated. It is important to continuously assess the current state of knowledge on COPD early detection, given the challenges associated with identifying undiagnosed COPD. This review aims to highlight recent advances in early detection of COPD. To discuss the current challenge and opportunity in COPD early detection, providing an overview of existing literature on COPD case-finding strategies, including the approaches, criteria for subjects, and instruments. The review also summarizes the current progress in COPD case-findings and proposes a COPD case-finding flowchart as an efficient method for identifying at risk COPD patients.

The Benefits of Molnupiravir Treatment in Healthcare Facilities Patients with COVID-19.

Background: Molnupiravir (MOL) is an oral antiviral medication that has recently been treated for COVID-19. Objectively: We perform a prospective and observational study to elucidate the efficacy and safety of MOL in healthcare patients with COVID-19. Materials and Methods: A observational, non-randomized study of patients diagnosed with COVID-19 in 46 healthcare facilities and treated with MOL started within 5 days after the onset of signs or symptoms. We recorded data for all patients, including demographic data, clinical features, and symptoms. Treatment response was classified into cure, stable, hospitalization and death. Multivariate analysis was performed with stepwise logistic regression for hospitalization and death risk factors. Results: In total, 856 patients were diagnosed as having COVID-19 and treated with MOL during the study period. Of those, 496 patients (57.9%) were cured, 256 patients (29.9%) in stable condition, 104 patients (12.2%) hospitalized, and 22 patients (2.6%) died, respectively. There was significant effectiveness (87.8%) in COVID-19 patients using MOL. Multivariate analysis was performed to confirm the risk factors for hospitalization and death and included elder age (>80 years old) (odds ratio (OR) 2.2, 95% confidence interval (CI): 1.1-6.9), old cerebrovascular accident (CVA) (OR=4.1, 95% CI: 1.3-9.9), the presence of diabetes mellitus (DM) (OR=2.6, 95% CI: 1.2-9.1) and chronic respiratory diseases (OR=2.4, 95% (CI): 1.3-8.1). Limitations: This is an observational study, neither randomized study nor control group study. Conclusion: Initial treatment with MOL has the treatment benefits and is well tolerated for patients with COVID-19 in healthcare facilities. Older age, old CVA, DM, and chronic respiratory diseases were independent risk factors for hospitalization and mortality. The results demonstrate there are important clinical benefits of MOL beyond the reduction in hospitalization or death for these patients with more comorbidities in Taiwan.

Asthma and COVID-19 Associations: Focus on IgE-Related Immune Pathology.

Management of patients with asthma during the coronavirus disease 2019 (COVID-19) pandemic is a concern, especially since asthma predisposes patients to respiratory problems. Interestingly, asthma characterized by type 2 inflammation, also known as T-helper type 2-high endotype, displays a cellular and molecular profile that may confer protective effects against COVID-19. The results of experimental and clinical studies have established the actions of immunoglobulin E (IgE) in inducing airway hyperreactivity and weakening an interferon-mediated antiviral response following respiratory viral infection. Robust evidence supports the beneficial effect of the anti-IgE biologic treatment omalizumab on reducing respiratory virus-induced asthma exacerbations and reducing the frequency, duration, and severity of respiratory viral illness in patients with asthma. Indeed, accumulating reports of patients with severe asthma treated with omalizumab during the pandemic have reassuringly shown that continuing omalizumab treatment during COVID-19 is safe, and in fact may help prevent the severe course of COVID-19. Accordingly, guidance issued by the Global Initiative for Asthma recommends that all patients with asthma continue taking their prescribed asthma medications, including biologic therapy, during the COVID-19 pandemic. The impact of biologic treatments on patients with asthma and COVID-19 will be better understood as more evidence emerges.