Using Machine Learning with Impulse Oscillometry Data to Develop a Predictive Model for Chronic Obstructive Pulmonary Disease and Asthma.

We aimed to develop and validate a machine learning model using impulse oscillometry system (IOS) profiles for accurately classifying patients into three assessment-based categories: no airflow obstruction, asthma, and chronic obstructive pulmonary disease (COPD). Our research questions were as follows: (1) Can machine learning methods accurately classify obstructive disease states based solely on multidimensional IOS data? (2) Which IOS parameters and modeling algorithms provide the best discrimination? We used data for 480 patients (240 with COPD and 240 with asthma) and 84 healthy individuals for training. Physiological and IOS parameters were combined into six feature combinations. The classification algorithms tested were logistic regression, random forest, neural network, k-nearest neighbor, and support vector machine. The optimal feature combination for identifying individuals without pulmonary obstruction, with asthma, or with COPD included 15 IOS and physiological features. The neural network classifier achieved the highest accuracy (0.786). For discriminating between healthy and unhealthy individuals, two combinations of twenty-three features performed best in the neural network algorithm (accuracy of 0.929). When distinguishing COPD from asthma, the best combination included 15 features and the neural network algorithm achieved an accuracy of 0.854. This study provides compelling technical evidence and clinical justifications for advancing IOS data-driven models to aid in COPD and asthma management.

Assessment of antibiotic resistance patterns in Central Taiwan during the COVID-19 pandemic: A retrospective study.

BACKGROUND: Antimicrobial resistance (AMR) is a growing worldwide public health issue due to the overuse and inappropriate use of antibiotics. AMR has been more prevalent during the coronavirus pandemic of 2019 (COVID-19) compared to previous periods. Therefore, this study was conducted to evaluate the AMR profile of common bacteria that were isolated for routine analysis during the pandemic of COVID-19 in Central Taiwan. The main goal of this study was to examine and analyze the AMR patterns both before and after the start of the COVID-19 pandemic. METHODS: We conducted a retrospective analysis of clinical samples collected from two different time periods: the 1-year period before the onset of the COVID-19 pandemic (January 2019 to December 2019) and the 2-year period following the start of the pandemic (September 2020 to September 2022). The data for this study were obtained from clinical records, and both bacterial identification and antibiotic susceptibility testing were performed using the Phoenix identification system. RESULTS: Among the 8152 bacterial isolates obtained during the study period from September 2020 to September 2022, 4022 (49.3%) were Escherichia coli, 1346 (16.5%) were Klebsiella pneumoniae, 1156 (14.2%) were Staphylococcus aureus, 887 (10.9%) were Pseudomonas aeruginosa, 376 (4.6%) were Enterococcus faecium, and 365 (4.5%) were Acinetobacter baumannii. The overall prevalence of resistant bacteria during the COVID-19 pandemic was as follows: vancomycin-resistant Enterococcus, 69%; carbapenem-resistant A. baumannii, 65%; methicillin-resistant S. aureus, 49%; carbapenem-resistant K. pneumoniae, 29%; carbapenem-resistant P. aeruginosa, 17%; and carbapenem-resistant E. coli, 2%. Carbapenem-resistant A. baumannii, vancomycin-resistant Enterococcus, carbapenem-resistant K. pneumoniae, and carbapenem-resistant E. coli increased by 19%, 10%, 2%, and 1%, respectively. On the other hand, carbapenem-resistant P. aeruginosa and methicillin-resistant S. aureus decreased by 6%, respectively. CONCLUSION: This study provides a comprehensive assessment of AMR during the COVID-19 pandemic in Central Taiwan. Understanding the prevalence of AMR is crucial for preventing infection and formulating disease prevention policies. Further research is warranted to elucidate the correlation between AMR and the severity of infection in COVID-19 patients.

Angiotensin-(1-7) attenuates SARS-CoV2 spike protein-induced interleukin-6 and interleukin-8 production in alveolar epithelial cells through activation of Mas receptor.

BACKGROUND: SARS-CoV-2 spike proteins (SP) can bind to the human angiotensin-converting enzyme 2 (ACE2) in human pulmonary alveolar epithelial cells (HPAEpiC) and trigger an inflammatory process. Angiotensin-(1-7) may have an anti-inflammatory effect through activation of Mas receptor. This study aims to investigate whether SARS-CoV-2 SP can induce inflammation through ACE2 in the alveolar epithelial cells which can be modulated through angiotensin-(1-7)/Mas receptor axis. METHODS: HPAEpiC were treated with SARS-CoV-2 SP in the presence or absence of ACE2 antagonist-dalbavancin and Mas receptor agonist-angiotensin-(1-7). Proinflammatory cytokine production (IL-6 and IL-8) were measured at mRNA and protein levels. MAP kinase phosphorylation and transcription factor activation was determined by Western Blot. Mas receptor was blocked by either antagonist (A779) or knockdown (specific SiRNA). Experiments were replicated using A549 cells. FINDINGS: SARS-CoV-2 SP (5 µg/mL) significantly induced MAP kinase (ERK1/2) phosphorylation, downstream transcription factor (activator protein-1, AP-1) activation and cytokine production (IL-6 and IL-8) at both mRNA and protein levels. Pretreatment with dalbavancin (10 µg/mL), or angiotensin-(1-7) (10 µM) significantly reduced ERK1/2 phosphorylation, AP-1 activation, and cytokine production. However, these angiotensin-(1-7)-related protective effects were significantly abolished by blocking Mas receptor with either antagonist (A799,10 µM) or SiRNA knockdown. INTERPRETATION: SARS-CoV-2 SP can induce proinflammatory cytokine production, which can be inhibited by either ACE2 antagonist or Mas receptor agonist-angiotensin-(1-7). Angiotensin-(1-7)-related protective effect on cytokine reduction can be abolished by blocking Mas receptor. Our findings suggest that ACE2/angiotensin-(1-7)/Mas axis may serve as a therapeutic target to control inflammatory response triggered by SARS-CoV-2 SP.

Assessing the prognostic value of respiratory oscillometry in patients with difficult-to-treat asthma.

Respiratory oscillometry is widely explored in asthma management; however, there is currently no consensus on its routine work-up in patients with difficult-to-treat asthma. We conducted a retrospective, cross-sectional study involving patients with difficult-to-treat asthma at Asia University Hospital between January 2017 and October 2020. We aimed to correlate clinical significance of respiratory oscillometry and asthma treatment outcomes including symptoms control and exacerbation in patients with difficult-to-treat asthma. Among the 69 patients enrolled in the study, a total of 26.1% of the patients experienced at least one severe or two moderate exacerbations. Patients with ACT < 20 presented a higher prevalence of higher frequency-dependent resistance (FDR; the difference in resistance at 5 Hz and 20 Hz) and frequency of resonance (Fres) than those with ACT ≥ 20. In the multivariable analysis, comorbidities, COPD or allergic rhinitis, and FDR were independent factors in increasing the odds ratio in poorly controlled asthma. (FDR ≥ 0.10 vs. < 0.10, adjusted ORR = 5.05, P = 0.037) There was a higher proportion of frequent exacerbations in patients with higher FDR (FDR ≥ 0.10 vs. < 0.10 = 30.0%:20.7%), but IOS parameters failed to predict frequent exacerbations on further analysis. FDR may be a potential clinical parameter for predicting symptom control in patients with difficult-to-treat asthma.

Inhibition of the clinical isolates of Acinetobacter baumannii by Pseudomonas aeruginosa: In vitro assessment of a case-based study.

BACKGROUND: The global rise in nosocomial infections associated with gram-negative bacteria and the spread of multi-drug resistant Acinetobacter baumannii (MDR-AB) pose public health concerns. This study investigates the inhibitory effects and possible inhibitory mechanism of Pseudomonas aeruginosa (PA) on selected clinical strains of A. baumannii (AB) isolated from Taiwanese patients. METHODS: Four and eight clinical strains of AB and PA, respectively, were randomly selected from the bacterial collection of Feng-Yuan Hospital, Taiwan. Antimicrobial-susceptibility was performed on the AB strains. Inhibition potential of the PA strains against AB was assessed by measuring the inhibition zones. In vitro analysis using phenazine-1-carboxamide (PCN) was conducted to assess the possible inhibitory mechanism of PA, which was later confirmed in the clinical isolates by liquid chromatography-mass spectrometry. RESULTS: All the clinical AB strains showed resistance to the eleven antibiotics and were classified as MDR-AB. The nine PA strains exert either a high (PA3596, PA3681, PA3772, and ATCC27853) or a low (PA3613, PA3625, PA3712, PA3715, and PA3744) degree of inhibition against AB strains. 0.25 mg/ml PCN had a clearer inhibition zone than 0.05 mg/ml PCN, suggesting a dose-dependent inhibition of PCN on the AB strains. The four PA strains that demonstrated a high degree of inhibition had a relatively high amount of PCN. CONCLUSION: Selected strains of PA exert inhibitory actions on MDR-AB with PCN being a possible inhibitory agent. This finding raises the possibility of developing effective therapeutic antibiotics and disinfectant from specific components of PA for the treatment and control of Acinetobacter-associated infections in hospital settings.

Association of TIMP-2 Rs8179090 Genotypes With Lung Cancer Risk in Taiwan.

BACKGROUND/AIM: The tissue inhibitor of metalloproteinase-2 (TIMP-2) is a critical inhibitor of matrix metalloproteinases (MMPs). Along with MMPs, TIMP-2 regulates the breakdown and remodeling of the extracellular matrix (ECM) and basement membranes. This study investigated the role of genotypes of the TIMP-2 -418G/C (rs8179090) single nucleotide polymorphism on lung risk. MATERIALS AND METHODS: A total of 358 lung cancer patients and 716 healthy subjects were recruited in this study. Genotypes were identified via the polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS: The distribution of alleles and genotype frequencies of TIMP-2 -418G/C genotypes between the two groups were compared and no statistically significant difference (p>0.05) was found. The heterozygous and homozygous variant genotypes showed no differential distribution between the control and case groups (p>0.05). CONCLUSION: TIMP-2 -418G/C variants might not be associated with lung cancer susceptibility and could not serve as predictors.

Benchmarking of eight recurrent neural network variants for breath phase and adventitious sound detection on a self-developed open-access lung sound database-HF_Lung_V1.

A reliable, remote, and continuous real-time respiratory sound monitor with automated respiratory sound analysis ability is urgently required in many clinical scenarios-such as in monitoring disease progression of coronavirus disease 2019-to replace conventional auscultation with a handheld stethoscope. However, a robust computerized respiratory sound analysis algorithm for breath phase detection and adventitious sound detection at the recording level has not yet been validated in practical applications. In this study, we developed a lung sound database (HF_Lung_V1) comprising 9,765 audio files of lung sounds (duration of 15 s each), 34,095 inhalation labels, 18,349 exhalation labels, 13,883 continuous adventitious sound (CAS) labels (comprising 8,457 wheeze labels, 686 stridor labels, and 4,740 rhonchus labels), and 15,606 discontinuous adventitious sound labels (all crackles). We conducted benchmark tests using long short-term memory (LSTM), gated recurrent unit (GRU), bidirectional LSTM (BiLSTM), bidirectional GRU (BiGRU), convolutional neural network (CNN)-LSTM, CNN-GRU, CNN-BiLSTM, and CNN-BiGRU models for breath phase detection and adventitious sound detection. We also conducted a performance comparison between the LSTM-based and GRU-based models, between unidirectional and bidirectional models, and between models with and without a CNN. The results revealed that these models exhibited adequate performance in lung sound analysis. The GRU-based models outperformed, in terms of F1 scores and areas under the receiver operating characteristic curves, the LSTM-based models in most of the defined tasks. Furthermore, all bidirectional models outperformed their unidirectional counterparts. Finally, the addition of a CNN improved the accuracy of lung sound analysis, especially in the CAS detection tasks.

Association between asthma and risk of benign prostatic hyperplasia: a retrospective population-based study.

OBJECTIVE: The association between asthma and benign prostatic hyperplasia (BPH) has rarely been explored. We investigated whether male asthmatic patients had an increased risk of BPH by conducting this retrospective nationwide population-based study. METHODS: We utilized data derived from the National Health Insurance Research Database (NHIRD) in Taiwan. A total of 9778 male patients aged >40 years who were newly diagnosed with asthma between 2000 and 2006 were included in the asthma group. Male enrollees without asthma were selected as the non-asthma group from the same database. Both the groups were followed up until the end of 2013. We performed Cox proportional hazard regression analysis to estimate the risk of BPH and transurethral resection of the prostate (TURP) in the male patients with asthma compared with that in those without asthma. RESULTS: The risk of BPH and TURP in the asthma group was 1.40-fold (95% confidence interval [CI] = 1.30-1.42) and 1.30-fold (95% CI= 1.31-1.50) higher than that in the non-asthma group, respectively, after adjusting for comorbidities, relevant medications and number of annual outpatient visits. CONCLUSIONS: The male patients with asthma were found to have a higher risk of BPH than did those without asthma.

Asthma is associated with endometriosis: A retrospective population-based cohort study.

BACKGROUND: Evidence regarding the association between asthma and endometriosis is limited and inconsistent. The goal of the study was to investigate whether women diagnosed as having asthma were at a greater risk of endometriosis than age-matched unaffected women. METHODS: We conducted a nationwide population-based retrospective study by using data retrieved from the Taiwan National Health Insurance Research Database during the period of 2000-2005 with follow-up through 2013. The current analysis included 7337 women aged 12-50 years with newly diagnosed asthma and using asthma-related medications and 29,348 age-matched women without asthma. A Cox proportional hazards regression model was used to estimate the risks of endometriosis in women with asthma as compared with those without asthma. RESULTS: The overall risk of endometriosis in the asthma group was 1.50-fold higher (95% confidence interval = 1.33-1.70) than that in the nonasthma group. A stratified analysis by age further revealed that patients with asthma were associated with a higher risk of endometriosis in age groups of 21-50 years. CONCLUSION: Compared with women without asthma, women with asthma of reproductive age are at a higher risk of endometriosis. Additional studies are warranted to elucidate the mechanism(s) underlying the association between asthma and a higher risk of endometriosis.

Association between chronic obstructive pulmonary disease and increased risk of benign prostatic hyperplasia: a retrospective nationwide cohort study.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) and benign prostatic hyperplasia (BPH) are common disorders in ageing male populations. Nevertheless, the relationship between the two diseases has rarely been explored. The objective of this study was to examine whether patients with COPD are at an increased risk of BPH. DESIGN: Retrospective nationwide cohort study. SETTING: Data retrieved from the Taiwan National Health Insurance Research Database. PARTICIPANTS: Overall, 19 959 male patients aged 40 years and over with newly diagnosed COPD between 2000 and 2006 were included as the COPD group, and 19 959 sex-matched and age-matched enrollees without COPD were included as the non-COPD group. Both groups were followed-up until the end of 2011. OUTCOME MEASURES: A Cox proportional hazards regression model was used to compute the risk of BPH in patients with COPD compared with enrollees without COPD. RESULTS: The overall incidence rate of BPH was 1.53 times higher in the COPD group than that in the non-COPD group (44.7 vs 25.7 per 1000 person-years, 95% CI 1.46 to 1.60) after adjusting for covariates. An additional stratified analysis revealed that this increased risk of BPH in patients with COPD remained significantly higher than that in enrollees without COPD in all men aged 40 years and over. CONCLUSION: After adjustment for covariates, male patients with COPD were found to be at a higher risk of BPH. We suggest that clinicians should be cautious about the increased risk of BPH in male patients with COPD.

Achieving zero waste of municipal incinerator fly ash by melting in electric arc furnaces while steelmaking.

The main objective of this work was to promote zero waste of municipal incinerator fly ash (MIFA) by full-scale melting in electric arc furnaces (EAFs) of steel mini mills around the world. MIFA, generally, is considered as a hazardous waste. Like in many countries, MIFA in Taiwan is first solidified/stabilized and then landfilled. Due to the scarcity of landfill space, the cost of landfilling increases markedly year by year in Taiwan. This paper presents satisfactory results of treating several hundred tons of MIFA in a full-scale steel mini mill using the approach of "melting MIFA while EAF steelmaking", which is somewhat similar to "molten salt oxidation" process. It was found that this practice yielded many advantages such as (1) about 18wt% of quicklime requirement in EAF steelmaking can be substituted by the lime materials contained in MIFA; (2) MIFA would totally end up as a material in fractions of recyclable EAF dust, oxidized slag and reduced slag; (3) no waste is needed for landfilling; and (4) a capital cost saving through the employment of existing EAFs in steel mini mills instead of building new melting plants for the treatment of MIFA. Thus, it is technically feasible to achieve zero waste of MIFA by the practice of this innovative melting technology.

Tuning perovskite morphology by polymer additive for high efficiency solar cell.

Solution processable planar heterojunction perovskite solar cell is a very promising new technology for low cost renewable energy. One of the most common cell structures is FTO/TiO2/CH3NH3PbI3-xClx/spiro-OMeTAD/Au. The main issues of this type of solar cell are the poor coverage and morphology control of the perovskite CH3NH3PbI3-xClx film on TiO2. For the first time, we demonstrate that the problems can be easily resolved by using a polymer additive in perovskite precursor solution during the film formation process. A 25% increase in power conversion efficiency at a value of 13.2% is achieved by adding 1 wt % of poly(ethylene glycol) in the perovskite layer using a 150 °C processed TiO2 nanoparticle layer. The morphology of this new perovskite was carefully studied by SEM, XRD, and AFM. The results reveal that the additive controls the size and aggregation of perovskite crystals and helps the formation of smooth film over TiO2 completely. Thus, the Voc and Jsc are greatly increased for a high efficiency solar cell. The amount of additive is optimized at 1 wt % due to its insulating characteristics. This research provides a facile way to fabricate a high efficiency perovskite solar cell by the low temperature solution process (<150 °C), which has the advancement of conserving energy over the traditional high temperature sintering TiO2 compact layer device.

Molecular typing and epidemiology of Clostridium difficile in respiratory care wards of central Taiwan.

BACKGROUND/PURPOSE: In industrialized countries, Clostridium difficile is the major cause of nosocomial diarrhea. This study involved a broad overview of baseline epidemiology for C. difficile in Taiwan. MATERIALS AND METHODS: Point prevalence was estimated from a prospective survey conducted in the respiratory care wards of six hospitals in central Taiwan. Polymerase chain reaction (PCR) ribotyping and multiple-locus variable-number tandem-repeat analysis (MLVA) were performed on all toxigenic C. difficile isolates, including asymptomatic and symptomatic strains. RESULTS: A total of 149 patients were screened for C. difficile; the point prevalence for C. difficile infection (CDI) and C. difficile colonization was 4% and 19%, respectively. CDI cases were significantly related to end-stage renal disease, and C. difficile colonization cases were significantly associated with previous admission to an acute-care facility. No hypervirulent PCR ribotype 027 strain was found. MLVA detected two clusters of CDI-related and three clusters of asymptomatic C. difficile strains circulating in wards. CONCLUSION: Our results demonstrate a high prevalence of toxigenic C. difficile colonization in hospitals. Infection control personnel should pay attention to the increasing numbers of CDI cases, and molecular typing for C. difficile should be performed when necessary.

Synergistic activities of tigecycline with clarithromycin or amikacin against rapidly growing mycobacteria in Taiwan.

The occurrence of diseases caused by rapidly growing mycobacteria (RGM) is increasing in Taiwan. In this study, the in vitro antimicrobial activities of tigecycline, minocycline, tetracycline and doxycycline were evaluated against 160 clinical RGM isolates, including 34 Mycobacterium abscessus sensu stricto (s.s.), 44 Mycobacterium massiliense, 1 Mycobacterium bolletii, 58 Mycobacterium fortuitum and 23 Mycobacterium chelonae. Clarithromycin and amikacin were tested alone as well as for synergistic effect with tigecycline. Both amikacin and tigecycline showed excellent activities against the RGM. More than 85% of each of the five RGM species isolates showed susceptibility to the two drugs. The MIC50 and MIC90 values (drug concentrations at which 50% and 90%, respectively, of the tested isolates did not show any visible growth) of amikacin were 1-4 mg/L and 2-8 mg/L, respectively, whilst those of tigecycline were 0.125-1 mg/L and 0.5-2.0 mg/L. Clarithromycin had only moderate activity, with ≥42.9% but ≤87.5% of each RGM species isolates showing susceptibility. The other three drugs had limited or no antimicrobial activity, with <40% of each RGM species isolates showing susceptibility. Combined with clarithromycin, tigecycline had synergistic activity against 92.9%, 68.8%, 100%, 35.7% and 46.2% of M. abscessus s.s., M. massiliense, M. bolletii, M. fortuitum and M. chelonae isolates, respectively. However, tigecycline combined with amikacin had synergistic activity against <25% but antagonistic activity against >18% of each RGM species. Thus, tigecycline alone may be an alternative for treating RGM diseases in patients who are intolerant to cefoxitin, imipenem or amikacin. However, it should be used with caution or not used in combination with amikacin for RGM diseases.

Respiratory deposition model of an inhaled aerosol bolus.

The bolus delivery method is designed to deliver a dose to the desired location in the lung, and it has the advantage of fewer side effects and a more efficient way of delivery. Based upon the lung deposition model developed for continuously inhaling aerosols of constant concentration, a mathematical model of aerosol bolus deposition is proposed. The calculated results show that the recovery depends on the bolus penetration depth, flow rate, particle size, breath holding time and bolus volume. Three sets of published experimental data with different controlling factors (particle size, flow rate and breath holding time) are adopted to make the quantitative comparisons with the calculated results. The predictions and data for the low intrinsic motion particles (∼1 µm) have good agreement, as do the coarse particles in the shallow airways region. For females, the recovery was found to be consistently lower than that for males.