Environmental risks and sphingolipid signatures in adult asthma and its phenotypic clusters: a multicentre study.

BACKGROUND: Adult asthma is phenotypically heterogeneous with unclear aetiology. We aimed to evaluate the potential contribution of environmental exposure and its ensuing response to asthma and its heterogeneity. METHODS: Environmental risk was evaluated by assessing the records of National Health Insurance Research Database (NHIRD) and residence-based air pollution (particulate matter with diameter less than 2.5 micrometers (PM2.5) and PM2.5-bound polycyclic aromatic hydrocarbons (PAHs)), integrating biomonitoring analysis of environmental pollutants, inflammatory markers and sphingolipid metabolites in case-control populations with mass spectrometry and ELISA. Phenotypic clustering was evaluated by t-distributed stochastic neighbor embedding (t-SNE) integrating 18 clinical and demographic variables. FINDINGS: In the NHIRD dataset, modest increase in the relative risk with time-lag effect for emergency (N=209 837) and outpatient visits (N=638 538) was observed with increasing levels of PM2.5 and PAHs. Biomonitoring analysis revealed a panel of metals and organic pollutants, particularly metal Ni and PAH, posing a significant risk for current asthma (ORs=1.28-3.48) and its severity, correlating with the level of oxidative stress markers, notably Nε-(hexanoyl)-lysine (r=0.108-0.311, p<0.05), but not with the accumulated levels of PM2.5 exposure. Further, levels of circulating sphingosine-1-phosphate and ceramide-1-phosphate were found to discriminate asthma (p<0.001 and p<0.05, respectively), correlating with the levels of PAH (r=0.196, p<0.01) and metal exposure (r=0.202-0.323, p<0.05), respectively, and both correlating with circulating inflammatory markers (r=0.186-0.427, p<0.01). Analysis of six phenotypic clusters and those cases with comorbid type 2 diabetes mellitus (T2DM) revealed cluster-selective environmental risks and biosignatures. INTERPRETATION: These results suggest the potential contribution of environmental factors from multiple sources, their ensuing oxidative stress and sphingolipid remodeling to adult asthma and its phenotypic heterogeneity.

NICEFIT-A Prospective, Non-Interventional, and Multicentric Study for the Management of Idiopathic Pulmonary Fibrosis with Antifibrotic Therapy in Taiwan.

Idiopathic pulmonary fibrosis (IPF) causes progressive lung fibrosis with subsequent fatality and has limited treatment options. NICEFIT is the first Taiwan-based prospective, observational, and non-interventional registry for IPF progression under routine clinical practice in Taiwan. Data on 101 patients (aged 74.6 ± 9.1 years and 83.2% men) with IPF were collected over 2 years (2018-2020) from medical centers in Taiwan at baseline, 1 month, and subsequent 3-month intervals. Treated patients (n = 88) received the antifibrotics nintedanib or pirfenidone, compared with the untreated group (n = 13). The 2-year assessment revealed overall preserved lung functionality in the treated patients, with insignificant changes from baseline for percent predicted forced vital capacity or FVC (±1.7%). The presence of respiratory comorbidities significantly increased the risk of both AE and death (with or without AE) over the full study duration. Furthermore, the decline of predicted FVC significantly increased with the risk of acute exacerbations (AE) in the second year. Overall, antifibrotic medication was beneficial in stalling IPF progression, reducing AEs, and delaying mortality in the treated cohort, despite their lower baseline lung functions. Further, no new safety concerns over antifibrotic treatments were observed for the Taiwanese population.

The Effectiveness and Tolerability of Glycopyrronium for Patients with Chronic Obstructive Pulmonary Disease in a Clinical Setting: GLARE-Taiwan.

Glycopyrronium (GLY) is a pharmacological maintenance treatment for chronic obstructive pulmonary disease (COPD). However, its effectiveness and tolerability for COPD patients in routine clinical practice have not been well-investigated. This study aimed to assess the effectiveness of GLY on health-related quality of life and its safety in patients with COPD in a routine clinical care setting. This multi-center, prospective, six-month observational study recruited patients diagnosed with COPD and treated with GLY at three medical centers in central Taiwan. The full analysis set (n = 102) had a significant improvement in the Clinical COPD Questionnaire total (mean ± SD = −0.39 ± 0.90, p = 0.002), symptoms (mean ± SD = −0.61 ± 0.90, p < 0.001) and mental state scores (mean ± SD = −0.54 ± 1.72, p = 0.021) but not the functional state score (mean ± SD = −0.10 ± 1.15, p = 0.529). During the observational period, 58 patients (52.73%) experienced adverse events; only one adverse event (dizziness) was suspected to be related to the study drug. Three patients (2.73%) discontinued the study and GLY treatment because of an adverse event. One patient (0.91%) died during the study period because of a cerebral infarction, which was judged to be not associated with GLY treatment. In conclusion, GLY could be effective in improving the health status and is safe for patients with COPD in a real-life setting.

Relationship between exposure to ozone and exacerbation requiring hospital admission among patients with asthma: a case-control study in central Taiwan.

OBJECTIVE: The convergence of asthma and air pollutants in ageing populations is currently a growing health issue worldwide, and hence there is an essential need to investigate the association between exposure to air pollution, particularly ozone (O3), and exacerbation requiring admission in patients with asthma. SETTING: A case-control study at a tertiary referral hospital in central Taiwan. PARTICIPANTS: We used an asthma cohort, which included 11 400 patients with asthma, for the period 2006-2018 at Taichung Veterans General Hospital. PRIMARY AND SECONDARY OUTCOME MEASURES: We identified patients who had admitted for exacerbation as cases and selected patients with asthma without exacerbation, matching (1:4) the cases for age, gender and season of exacerbation, as controls. Data on hourly level of air pollutants were obtained from the Taiwan Environmental Protection Administration. We used conditional logistic regression and calculated adjusted ORs (adjORs) with 95% CIs. RESULTS: We enrolled 11 400 participants with asthma, and 4.4% (501) of them had been admitted for exacerbation. Participants with asthma with exacerbation requiring hospitalisation were exposed to a higher level of O3 8-hour daily maximum (adjOR 1.009, 95% CI 1.001 to 1.016) and were more likely to have high Charlson Comorbidity Index (CCI ≥3; adjOR 2.198, 95% CI 1.729 to 2.794) and asthma-chronic obstructive pulmonary disease overlap (adjOR 4.542, 95% CI 3.376 to 6.611) compared with those without exacerbation. The aforementioned associations between exacerbation of asthma requiring hospitalisation and exposure to O3 were similar when defined by either O3 1-hour daily maximum or O3 24-hour average. Moreover, the O3 relevant exacerbation of asthma mainly existed in those aged older than 65 years and patients with medical comorbidities, including gastrointestinal diseases, cardiovascular diseases, neurological diseases, diabetes and renal disease. CONCLUSIONS: Our findings highlight the need for vigilance of exposure to O3 among elderly with asthma, particularly those with medical comorbidities. Further studies are warranted to investigate the underlying mechanisms.

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.

The Long-Term Effectiveness of Omalizumab in Adult Patients with Severe Allergic Asthma: Continuous Treatment Versus Boosting Treatment.

The implications of boosting Omalizumab treatment (OT) in patients with severe allergic asthma (SAA) remain unclear. The study aimed to explore and compare the 12-month effectiveness between continuous, at least 10-month OT (continuation group) and four-month boost of Omalizumab (boost group) in adult patients with SAA. In this retrospective cohort study, clinical data were collected for further analysis. Of all participants (n = 124), a significant reduction in annual exacerbations (baseline = 0.8 ± 1.5, follow-up = 0.5 ± 1.0, p = 0.047 *) and improvement in small airway ventilation as evaluated by forced expiratory flow at 25-75% (baseline = 55.1 ± 11.1%, follow-up = 59.4 ± 8.4%, p < 0.001 *) were found in the continuation group (n = 110). By contrast, the boost group (n = 14) had significantly increased annual exacerbations (baseline = 0.7 ± 1.4, follow-up = 2.9 ± 3.6, p = 0.031 *) and impaired small airway function (baseline = 55.3 ± 12.9, follow-up = 52.1 ± 12.5, p = 0.026 *). Furthermore, the continuation group rather than the boost group had significant decreases in the frequency of oral corticosteroid (OCS) use as controllers (baseline = 32.7%, follow-up = 20.0%, p = 0.047 *; baseline = 50.0%, follow-up = 21.4%, p = 0.237, respectively) and OCS maintenance dose (mg/month) (baseline = 85.9 ± 180.8, follow-up = 45.8 ± 106.6, p = 0.020 *; baseline = 171.4 ± 221.5, follow-up = 50.0 ± 104.3, p = 0.064, respectively), and increases in asthma control test scores (baseline = 16.0 ± 3.0, follow-up = 19.8 ± 4.4, p < 0.001 *; baseline = 14.6 ± 3.8, follow-up = 19.7 ± 4.7, p = 0.050, respectively). Continuous OT would be beneficial for adult patients with SAA, while boost of Omalizumab would worsen their long-term outcomes.

Predictors of a Minimal Clinically Important Difference Following Omalizumab Treatment in Adult Patients With Severe Allergic Asthma.

Several factors have been found to be predictors of a good response following omalizumab treatment in patients with severe allergic asthma (SAA). However, it remains unclear whether clinical characteristics can predict a minimal clinically important difference (MCID) following omalizumab treatment in this population. Therefore, the aim of this study was to investigate the features associated with an MCID following omalizumab treatment in adult patients with SAA. Of the 124 participants enrolled in this retrospective, cross-sectional study, 94, 103, 20 and 53 achieved the MCID following treatment with omalizumab and were considered to be responders of exacerbation reduction (no exacerbation during the 1-year follow-up period or ≧50% reduction in exacerbations from baseline), oral corticosteroid (OCS) sparing (no use of OCS to control asthma during the study period or a reduction of the monthly OCS maintenance dose to <50% of baseline), lung function (an increase of ≧230 ml in the forced expiratory volume in 1 s from baseline) and asthma control (an increase of ≧3 points in the asthma control test score from baseline), respectively. Normal weight [<25 vs. ≧30 kg/m2, odds ratio (OR) = 3.86, p = 0.024] was predictive of a responder of reduction in exacerbations following omalizumab treatment while subjects with a blood eosinophil level of <300 cells/µL (<300 vs. ≧300 cells/µL, OR = 5.81, p = 0.001) were more likely to exhibit an MCID in OCS sparing. No factor was found to be a predictor of lung function or asthma control. When choosing treatment for adult patients with SAA, our findings may help to select those who may benefit the most from omalizumab treatment.

Budesonide/Formoterol Anti-Inflammatory Reliever and Maintenance or Fluticasone Propionate/Salmeterol Plus As-Needed, Short-Acting ß2 Agonist: Real-World Effectiveness in pAtients without Optimally Controlled asThma (REACT) Study.

INTRODUCTION: In the prospective, observational, 16-week REACT study conducted between October 21, 2008 and May 12, 2011, we compared the real-world effectiveness of anti-inflammatory reliever and maintenance therapy with budesonide/formoterol (Symbicort® Turbuhaler) and maintenance therapy with fixed-dose fluticasone/salmeterol (Seretide®) plus as-needed, short-acting ß2 agonists (SABAs) in Taiwanese patients with inadequate asthma control. METHODS: Asthma control was assessed using the five-item Asthma Control Questionnaire (ACQ-5) and standardized pulmonary function testing. Assessments were performed at baseline and at weeks 4-5 and 12-16. Overall, we enrolled 842 patients at 11 clinics, 723 of whom were included in analyses (budesonide/formoterol, 563.3±1.3 µg/d, n=551; fluticasone/salmeterol, 1013.8±1.4 µg/d, n=172). RESULTS: At baseline, 72.5% and 27.5% of all patients had "partly" and "uncontrolled" asthma, respectively. Mean±SD ACQ-5 scores were 1.54±1.06 and 1.46±1.28 in the budesonide/formoterol and fluticasone/salmeterol groups, respectively. ACQ-5 scores significantly improved from baseline (ie, decreased) in both groups at weeks 4 and 16. ACQ-5 difference scores were significantly lower in the budesonide/formoterol group (-0.91±1.11) than the fluticasone/salmeterol group (-0.69±1.27) at the end of the study (p=0.027). Peak expiratory flow rate significantly improved from baseline in the budesonide/formoterol but not the fluticasone/salmeterol group at the end of the study. Severe exacerbation rates and medical resource utilization were comparable between the budesonide/formoterol and fluticasone/salmeterol groups. CONCLUSION: Collectively, results indicate the real-world effectiveness of budesonide/formoterol anti-inflammatory reliever and maintenance therapy is better than fixed-dose fluticasone/salmeterol plus as-needed SABA. TRIAL REGISTRATION: ClinicalTrials.gov registration number: NCT00784953.

Dynamics of the lung microbiome in intensive care patients with chronic obstructive pulmonary disease and community-acquired pneumonia.

Little is known about the composition and clinical implications of lung microbiome in patients with chronic obstructive pulmonary disease (COPD) and community-acquired pneumonia requiring invasive mechanical ventilation and intensive care unit admission. Therefore, this study aimed to explore the longitudinal changes in microbial airway composition and its variations between COPD patients with different weaning outcomes. Fifty-one endotracheal aspirate samples from 21 participants and 5 saline samples were collected as the patient and control group, respectively. Sequence analysis revealed significant increases and upward trends in the relative abundance of the Acinetobacter genus and Acinetobacter baumannii complex species in paired comparisons of sampling points and over time, respectively, in patients with failed weaning (p for trend = 0.012 and 0.012, respectively) but not in those with successful weaning (p for trend = 0.335 and 0.426, respectively). Furthermore, significant changes in the composition of the bacterial community were observed in paired comparisons of sampling points in patients with failed weaning compared with those with successful weaning. The alpha diversity did not differ between the patients with different weaning outcomes. These results further the understanding of longitudinal airway microbiome structure analysis and its clinical implications when managing critically ill patients with and without COPD.

Dynamic Changes in Prognosis with Elapsed Time on Ventilators among Mechanically Ventilated Patients.

Rationale: Previous outcome studies of mechanical ventilation usually adopted a static timeframe to observe the outcome and reported prognosis from the standpoint of the first ventilator day. However, patients and their families may repeatedly inquire about prognosis over time after the initiation of mechanical ventilation.Objectives: We aimed to describe dynamic changes in prognosis according to the elapsed time on a ventilator among mechanically ventilated patients.Methods: For this cohort study we used the entire population dataset of Taiwan's National Health Insurance database. We enrolled adults who newly received invasive mechanical ventilation for at least two consecutive days between March 1, 2010, and August 31, 2011. For every single ventilator day after the initiation of mechanical ventilation, we estimated the cumulative probabilities of weaning success and death in the subsequent 90 days.Results: A total of 162,200 episodes of respiratory failure requiring invasive mechanical ventilation were included. The median age of the subjects was 72 years (interquartile range 57-81 yr) and the median follow-up time was 250 days (interquartile range 30-463 d). The probability curve of weaning success against the time on ventilation showed a unidirectionally decreasing trend, with a relatively sharp slope in the initial 2 months. The probabilities of weaning success in 90 days after the 2nd, 7th, 21st, and 60th ventilator days were 68.3% (95% confidence interval [CI], 68.1-68.5%), 62.6% (95% CI, 62.2-62.9%), 46.3% (95% CI, 45.8-46.8%), and 21.0% (95% CI, 20.3-21.8%), respectively. In contrast, the death curve showed an initial increase and then a decreasing trend after the 19th ventilator day. We also reported tailored prognosis information according to the age, sex, and ventilator day of a mechanically ventilated patient.Conclusions: This study provides ventilator-day-specific prognosis information obtained from a large cohort of unselected patients on invasive mechanical ventilation. The probability of weaning success decreased with the elapsed time on mechanical ventilation, and the decline was particularly remarkable in the first 2 months of ventilatory support.

Distinct Physiological Characteristics of Isolated Laryngopharyngeal Reflux Symptoms.

BACKGROUND & AIMS: Patients with isolated laryngopharyngeal reflux symptoms (LPRS) defined as those without concomitant typical reflux symptoms (CTRS) are clinically challenging to manage due to unclear pathophysiology. We investigated esophageal physiology in patients with isolated LPRS and their response to proton-pump inhibitors (PPI) therapy. METHODS: This is a multi-center observational study conducted in referral hospitals in Taiwan. Patients with predominant LPRS, but without common non-reflux causes, underwent esophageal manometry, 24-hr ambulatory esophagopharyngeal pH testing, and Bernstein test, followed by a 12-week esomeprazole 40 mg twice-daily treatment. Participants with pathological reflux were divided into the isolated LPRS group (ie, LPRS without CTRS, n = 40) and the CTRS group (ie, LPRS with CTRS, n = 66). Participants without pathological reflux or esophagitis (n = 132) served as the nonreflux controls. RESULTS: The PPI-responsiveness was similar between the isolated LPRS group and CTRS group (63% vs 57%, P = .8), but lower in the nonreflux controls (32%, P = .005). Despite similar distal esophageal acid exposure time (P = .7) when compared to those with CTRS, the isolated LPRS group had a lower prevalence of both positive Bernstein test (P = .001) and ineffective esophageal motility disorder (P = .03), and fewer pharyngeal acid reflux episodes (P < .0001). CONCLUSIONS: Our findings indicate similar distal esophageal acid exposure and PPI-responsiveness between LPRS patients with and without CTRS. The lack of CTRS in the isolated LPRS group is likely due to esophageal acid hyposensitivity and fewer pharyngeal acid reflux episodes, thus implicating distinct pathophysiology of isolated LPRS from those with CTRS.

The association between airflow limitation and blood eosinophil levels with treatment outcomes in patients with chronic obstructive pulmonary disease and prolonged mechanical ventilation.

The clinical implications of airflow limitation severity and blood eosinophil level in patients with chronic obstructive pulmonary disease (COPD) and prolonged mechanical ventilation (PMV) are unknown. Thus, this study aimed to identify whether or not these two indicators were significantly associated with short-term in-respiratory care center (RCC) treatment outcomes in this population. Of all participants (n = 181) in this retrospective cross-sectional study, 41.4%, 40.9%, 8.3%, and 52.5% had prolonged RCC admission (RCC length of stay >21 days), failed weaning, death, and any adverse outcomes of interest, respectively. Compared to participants without any adverse outcomes of interest, moderate (the Global Initiative for Chronic Obstructive Lung Disease (GOLD) II) and/or severe (GOLD III) airflow limitation were significantly associated with short-term in-RCC adverse outcomes in terms of failed weaning (for III versus I, OR = 15.06, p = 0.003) and having any adverse outcomes of interest (for II versus I, OR = 17.66, p = 0.002; for III versus I, OR = 37.07, p = 0.000) though the severity of airflow limitation did not have associations with prolonged RCC admission and death after adjustment. Meanwhile, blood eosinophilia defined by various cut-off values was not associated with any adverse outcomes. The findings have significant clinical implications and are useful in the management of patients with COPD and PMV.

Shared prenatal impacts among childhood asthma, allergic rhinitis and atopic dermatitis: a population-based study.

BACKGROUND: Increasing prevalence of childhood allergic diseases including asthma is a global health concern, and we aimed to investigate prenatal risk factors for childhood asthma and to address the potential shared prenatal impacts among childhood asthma, allergic rhinitis (AR) and atopic dermatitis (AD). METHODS: We used two claim databases, including Taiwan Birth Cohort Study (TBCS) and National Health Insurance Research Database (NHIRD), to identify independent paired mother-child data (mother-child dyads) between 2006 and 2009. The association between prenatal factors and asthma was determined by calculating adjusted odds ratio (aOR) with 95% confidence interval (CI) using conditional logistic regression analysis. RESULTS: A total of 628,878 mother-child dyads were included, and 43,915 (6.98%) of children developed asthma prior to age 6. We found that male gender (aOR 1.50, 95% CI 1.47-1.53), maternal asthma (aOR 1.80, 95% CI 1.71-1.89), maternal AR (aOR 1.33, 95% CI 1.30-1.37), preterm birth (aOR 1.32, 95% CI 1.27-1.37), low birth weight (aOR 1.14, 95% CI 1.10-1.19) and cesarean section (aOR 1.10, 95% CI 1.08-1.13) were independent predictors for childhood asthma. A high urbanization level and a low number of older siblings were associated with asthma in a dose-response manner. Notably, we identified that the association between maternal asthma and childhood asthma (aOR 1.80, 95% CI 1.71-1.89) was stronger compared with those between maternal asthma and childhood AR (aOR 1.67, 95% CI 1.50-1.87) as well as childhood AD (aOR 1.31, 95% CI 1.22-1.40). Similarly, the association between maternal AR and childhood AR (aOR 1.62, 95% CI 1.53-1.72) was higher than those between maternal AR and childhood asthma (aOR 1.33, 95% CI 1.30-1.37) as well as childhood AD (aOR 1.35, 95% CI 1.31-1.40). Furthermore, the number of maternal allergic diseases was associated with the three childhood allergic diseases in a dose-response manner. CONCLUSIONS: In conclusion, this population-based study provided evidence of prenatal impacts on childhood asthma and demonstrated the shared maternal impacts among childhood asthma, AR, and AD. These findings highlight the shared prenatal impacts among allergic diseases, and studies are warranted to address the pivotal pathway in allergic diseases.

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.

The impact of 2011 and 2017 Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) guidelines on allocation and pharmacological management of patients with COPD in Taiwan: Taiwan Obstructive Lung Disease (TOLD) study.

BACKGROUND: This nationwide study was performed to evaluate the evolution of distributions of patients with COPD according to the 2011 and 2017 Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) guidelines and to assess the concordance between the prescribed medications and the pharmacological management recommended by the two distinct classification systems in Taiwan. SUBJECTS AND METHODS: Data were retrospectively retrieved from stable COPD patients in 11 participating hospitals across Taiwan. Patients were grouped according to GOLD 2011 and 2017 guidelines respectively. Definitions of undertreatment and overtreatment were based on the pharmacological recommendations in the individual guidelines. RESULTS: A total of 1,053 COPD patients were included. The percentages of patients in GOLD 2011 groups A, B, C and D were 18.4%, 40.6%, 6.7% and 34.2%, respectively. When reclassified according to the GOLD 2017, the percentages of group A and B increased to 23.3% and 63.2%, and groups C and D decreased to 1.9% and 11.6%, respectively. Up to 67% of patients in GOLD 2011 groups C and D were reclassified to GOLD 2017 groups A and B. The pharmacological concordance rate was 60.9% for GOLD 2011 and decreased to 44.9% for GOLD 2017. Overtreatment was found in 29.5% of patients according to GOLD 2011 and the rate increased to 46.1% when classified by the GOLD 2017. The major cause of overtreatment was unnecessary inhaled corticosteroids and the main cause of undertreatment was a lack of maintenance long-acting bronchodilators. CONCLUSION: The distribution of COPD patients in Taiwan was more uneven with the GOLD 2017 than with the GOLD 2011. A pharmacological discordance to the guidelines was identified. Updated guidelines with reclassification of COPD patients resulted in more discordance between prescribed medications and the guidelines. Physicians should make proper adjustments of the prescriptions according to the updated guidelines to ensure the mostly appropriate treatment for COPD patients.

Clinical features, bacteriology of endotracheal aspirates and treatment outcomes of patients with chronic obstructive pulmonary disease and community-acquired pneumonia in an intensive care unit in Taiwan with an emphasis on eosinophilia versus non-eosinophilia: a retrospective case-control study.

OBJECTIVES: The clinical implications of blood eosinophil level in patients with chronic obstructive pulmonary disease (COPD) and community-acquired pneumonia (CAP) requiring invasive mechanical ventilation (IMV) and intensive care unit (ICU) admission are still unknown. Thus, this study aimed to compare the features of such patients with and without blood eosinophilia. DESIGN: This was a retrospective case-control study. SETTING: An ICU of a medical centre in central Taiwan. PARTICIPANTS: A total of 262 patients with COPD and CAP requiring IMV and ICU admission. RESULTS: Of all participants (n=262), 32 (12.2%) had an eosinophil percentage (EP) >2% and 169 (64.5%) had an absolute eosinophil count (AEC) >300 cells/µL. Regardless of whether 2% or 300 cells/µL was used as a cut-off value, the eosinophilia group were slightly older (years) (82.9±5.4 vs 78.1±9.1, p=0.000 and 79.2±8.4 vs 77.6±9.6, p=0.246, respectively), and had a higher forced expiratory volume in 1 s/forced vital capacity (%) (56.0±8.0 vs 51.3±11.6, p=0.005 and 53.1±11.2 vs 49.5±11.2, p=0.013, respectively), less severe spirometric classification (p=0.008 and p=0.001, respectively), and lower white cell count 109/L (8.8±3.2 vs 11.1±4.9, p=0.009 and 10.3±4.4 vs 11.8±5.3, p=0.017, respectively) than the non-eosinophilia group. The bacteriology of endotracheal aspirates showed that Pseudomonas aeruginosa and other gram-negative bacilli were the most common organisms in all study groups. Participants with an EP >2% had a shorter ICU length of stay (OR=12.13, p=0.001) than those with an EP ≤2%, while an AEC >300 cells/µL was not associated with any in-ICUoutcomes. CONCLUSIONS: The results of this study have significant clinical implications and should be considered when making treatment decisions for the management of patients with COPD and CAP requiring IMV and ICU admission.

Characteristics and risk factors for inconsistency between the risk of exacerbations and the severity of airflow limitation in COPD based on GOLD 2017: A retrospective, cross-sectional study.

BACKGROUND AND OBJECTIVES: The clinical implications of the discordance between the risk of exacerbations and the level of airflow limitation in patients with chronic obstructive pulmonary disease (COPD) are still unknown. This study aimed to clarify the clinical significance of such discordance in the management of COPD by exploring its characteristics and risk factors. METHODS: In this retrospective, cross-sectional study, participating physicians completed a detailed patient record form for each participating outpatient with COPD. The data, collected by the Taiwan Obstructive Lung Disease consortium, were managed and analyzed. RESULTS: Of the enrolled participants, 316 (41.7%) had an inconsistency between the risk of exacerbations and the severity of airflow limitation. Univariate analysis showed that more severe airflow limitation (p = 0.000), higher COPD assessment test (CAT) scores (p = 0.003) and modified Medical Research Council (mMRC) scales (p = 0.008), and the presence of at least one (p = 0.000) or two (p = 0.003) co-morbidities were significantly associated with such inconsistency. More severe airflow limitation (Global Initiative for Chronic Obstructive Lung Disease (GOLD) 3 and 4 classification; odds ratio (OR) = 27.09, p = 0.000 and OR = 25.15, p = 0.000, respectively) and the presence of at least one co-morbidity (OR = 2.01, p = 0.001) were still associated with the inconsistency in multivariate logistic regression analysis. Furthermore, the presence of wheezing (OR = 3.90, p = 0.000) and at least two co-morbidities (OR = 5.43, p = 0.005) were independent risk factors for an inconsistency of a high risk of exacerbations / GOLD 1 or 2 and the CAT score≧10 (OR = 1.58, p = 0.007), mMRC scale 2-4 (OR = 1.53, p = 0.017), and the presence of at least one co-morbidity (OR = 2.55, p = 0.000) for an inconsistency of a low risk of exacerbations / GOLD 3 or 4. CONCLUSIONS: The patients with COPD and an inconsistency between the risk of exacerbations and level of airflow limitation had unique clinical characteristics and risk factors for this inconsistency. Management of these patients should include more detailed evaluations.

Comparative efficacy and tolerability of beclomethasone/formoterol and fluticasone/salmeterol fixed combination in Taiwanese asthmatic patients.

BACKGROUND: The study was designed to compare the efficacy and tolerability of a fixed combination of extra-fine beclomethasone and formoterol, with the fixed combination fluticasone and salmeterol in Taiwanese asthmatic patients. METHODS: This was a phase III, multicentre, randomized, two-arm parallel groups, controlled study. Patients with moderate to severe asthma were randomized to a 12-week treatment with either beclomethasone 100 mcg plus formoterol 6 mcg (BDP/F) or fluticasone 125 mcg plus salmeterol 25 mcg (FP/S), both delivered 2 inhalations twice daily. The efficacy and tolerability of these two combinations were compared. RESULTS: Among the 253 randomized subjects, 244 patients were evaluable (119 in the BDP/F group and 125 in the FP/S group). A significant improvement from baseline to the end of treatment period was observed in both BDP/F and FP/S groups in forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), morning and evening peak expiratory flow (PEF), Asthma Control Test (ACT) score and the use of rescue medication. FVC increase from pre-dose was significant after 5 min post inhalation in the BDP/F group only, while statistically significant within group improvement was not achieved until 30 min post inhalation in the FP/S group. CONCLUSION: The BDP/F combination is comparable in efficacy and tolerability to FP/S combination in Taiwanese asthmatic patients, with the advantage of rapid onset of improvement of FVC, consistent with the faster improvement of pulmonary hyperinflation with BDP/F.

The suitability of the GERDyzer instrument in pH-test-proven laryngopharyngeal reflux patients.

The use of validated patient-reported outcome (PRO) instruments for the treatment outcome measure of laryngopharyngeal reflux (LPR) is crucial given the lack of objective markers. However, current symptom-based PRO instruments can only partially capture the impact of LPR. The GERD Analyzer (GERDyzer), an existing disease-specific PRO instrument, which measures multidimensional health-related quality of life (HRQL) affected by the illness rather than by any specific symptoms, has been validated in patients with erosive gastroesophageal reflux disease (GERD). Following the U.S. Food and Drug Administration PRO guidance, we cross-culturally adapted the GERDyzer instrument into Chinese, and examined the qualitative and quantitative psychometric properties of the Chinese version GERDyzer in pH-test-proven LPR patients.The GERDyzer comprises 10 dimensions of HRQL, including general well-being, pain/discomfort, physical health, diet, energy, activities, leisure activities, social life, mood, and sleep. To examine the content validity, we recruited 26 pH-test-proven LPR participants to conduct 4 focus group meetings for direct patient input on clinical manifestations and HRQL impacts. We also tested the quantitative psychometric properties, including reliability, validity, and responsiveness in 100 pH-test-proven LPR patients.Saturation of concept elicitation was achieved from the 4 focus groups, and a strong conceptual match was evident between the GERDyzer contents and responses from the focus group participants. Cognitive debriefing assessment showed that the Chinese version GERDyzer was adequate for use by patients as it demonstrated linguistic validation and cultural harmonization. Quantitative psychometric properties showed evidence of high internal consistency (Cronbach α: 0.96), good to excellent test-retest reliability (intraclass correlation coefficient: 0.84-0.98). Confirmatory factor analysis supported a 2-factor structure. Convergent validity was confirmed by moderate correlation assessments referencing the Reflux Symptoms Index and the Reflux Questionnaire. The discriminant validity was supported by the ability to discriminate moderate-to-severe disease from mild disease. The responsiveness was also high in participants with and without typical GERD symptoms (effect sizes 1.20 and 1.21, respectively).In conclusion, the Chinese version GERDyzer instrument is a reliable, valid, and responsive instrument for assessing HRQL in Taiwanese patients with LPR.