Randomized, Double-blind, Phase III Trial of Lobeglitazone Add-on to Metformin in Type 2 Diabetes (SENSITIZE INDIA).

BACKGROUND: The efficacy and safety of lobeglitazone sulfate has been reported only in the Korean population, and no study has been conducted in India. MATERIALS AND METHODS: In this 16-week randomized, double-blind, and multicenter study, the efficacy and safety of lobeglitazone sulfate 0.5 mg were evaluated with pioglitazone 15 mg. Type 2 diabetes mellitus (T2DM) patients with ≥7.5% glycated hemoglobin (HbA1c) ≤10.5% and on stable metformin dose were assigned to both treatment arms. The primary outcome was a mean change in HbA1c. Safety assessments included adverse events (AE), home-based glucose monitoring, vital parameters, electrocardiogram (ECG), and laboratory assessments. RESULTS: A total of 328 subjects were randomized equally in two groups. A statistically significant reduction in HbA1c at week 16 in the lobeglitazone group with the least square (LS) mean change: 1.01 [standard error (SE): 0.09] (p < 0.0001) was seen. The LS mean difference between the two groups was 0.05 (SE: 0.12) [95% confidence interval (CI): -0.18, 0.27], which was statistically significant (p = 0.0013). Statistically significant reductions were also observed in fasting and postprandial glucose. Treatment-emergent Aes (TEAE) were comparable between both groups. CONCLUSION: Lobeglitazone 0.5 mg once daily was found to be efficacious and safe in the treatment of T2DM in the Indian population. Lobeglitazone significantly improved glycemic parameters and was noninferior to pioglitazone; hence, it could be a promising insulin sensitizer in T2DM management in India.

Correction to "SARS-CoV-2 accelerated clearance using a novel nitric oxide nasal spray (NONS) treatment: A randomized trial".

[This corrects the article DOI: 10.1016/j.lansea.2022.100036.].

SARS-CoV-2 accelerated clearance using a novel nitric oxide nasal spray (NONS) treatment: A randomized trial.

Background: Additional outpatient therapies which are readily accessible will be essential to reduce COVID-19 illness progression in high risk individuals. Especially as the virus continues to mutate with greater transmissibility despite increased global vaccination. Methods: A randomized, double-blind, multicentre, parallel group, placebo-controlled phase III clinical trial evaluated the ability of nitric oxide (NO) to rapidly eradicate nasal SARS-CoV-2 RNA. Adults (18-70 years) with mild symptomatic COVID-19 were randomized, confirmed by laboratory SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) nasal swab. Randomisation was 1:1, NONS (N = 153) vs placebo (N = 153). NO generated by a nasal spray (NONS) was self-administered six times daily as two sprays per nostril (0⋅45 mL of solution/dose) for seven days. Patients at high risk of illness progression, defined as unvaccinated, ≥ 45 years of age or having comorbidities, were the primary analysis population. Findings: Overall, mean SARS-CoV-2 RNA concentrations (6·96 log10 copies/mL in the NONS group and 7·16 log10 copies/mL in the placebo group) were comparable at baseline. Primary endpoint mean treatment difference SARS-CoV-2 RNA change from baseline to the end of treatment (EOT) was -0·52 copies/mL (SE 0·202, 95% CI -0·92 to -0·12; p = 0·010) with NONS compared to placebo. Secondary endpoint assessments demonstrated a greater proportion of patients receiving NONS (82·8%) cleared SARS-CoV-2 (RT-PCR negative) by EOT compared to placebo (66·7%, p = 0·046), with no virus RNA detected a median of four days earlier compared to placebo (three vs seven days; p = 0·044). Interpretation: Use of NONS in patients recently infected with SARS-CoV-2 accelerates nasal virus clearance. Funding: Funding provided by Glenmark Pharmaceuticals Limited. Study medication provided by SaNOtize.

Comparative efficacy and safety of glycopyrronium/formoterol fixed-dose combination versus glycopyrronium monotherapy in patients with moderate-to-severe COPD.

Background: The safety and efficacy of fixed-dose combination (FDC) of glycopyrronium bromide 12.5 µg/formoterol fumarate 12 µg (GB/FF) twice daily as dry powder inhalers (DPIs) compared to glycopyrronium 50 µg monotherapy (GLY) once daily as DPI in subjects with moderate-to-severe chronic obstructive pulmonary disease (COPD) were evaluated. Methods: This was a phase-3, randomized, double-blind, active-controlled, parallel-group, superiority study conducted in India. COPD patients aged ≥40 to ≤65 years, current or ex-smokers with FEV1/FVC <0.70, using ICS, LAMA, or LABA for ≥1 month were included. Subjects were randomized (1:1) to GB/FF or GLY for 12 weeks. The primary efficacy endpoint was the change from baseline in peak FEV1 at the end of 12 weeks. The study is registered with the Clinical Trials Registry of India (CTRI/2017/02/007814). Results: Between March 2017 and July 2018, 331 patients were enrolled and randomized into GB/FF FDC (165 patients) and GLY monotherapy (166 patients) groups. At week 12, the difference in change from baseline in the peak FEV1 for GB/FF DPI versus GLY was 0.115 L (SE = 0.02; 95% CI = 0.061, 0.170; P < 0.0001). Trough FEV1 increased significantly in the GB/FF group compared to the GLY group with a treatment difference of 0.078 L (SE = 0.02; 95% CI = 0.015, 0.14; P = 0.01). There were no significant differences in adverse events between the groups. Conclusion: FDC of GB/FF (12.5/12 µg twice daily) as a DPI provides superior bronchodilation and lung function improvement over GLY (50 µg once daily) monotherapy. It is safe and well tolerated in symptomatic COPD patients.

Efficacy and safety of single-inhaler triple therapy of glycopyrronium, formoterol and fluticasone in patients with COPD: a double-blind, randomised controlled trial.

BACKGROUND: The aim of this work was to investigate the safety and efficacy of single-inhaler triple therapy with 12.5 µg glycopyrronium (GB)/12 µg formoterol fumarate (FF)/250 µg fluticasone propionate (FP), compared to 50 µg GB co-administered with a fixed dose of 12 µg FF/250 µg FP in subjects with COPD. METHODS: This was a phase 3, randomised, double-blind, active-control, parallel-group, noninferiority study conducted at 20 sites across India. COPD patients aged ≥40 to ≤75 years, with forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <0.70, using mono/dual therapy with inhaled corticosteroids (ICSs), long-acting muscarinic antagonists (LAMAs), or long-acting ß-agonists (LABAs) for ≥1 month, were included. Subjects were randomised 1:1 to GB/FF/FP or GB+FF/FP for 12 weeks. The primary efficacy end-point was the change from baseline in trough FEV1 at the end of 12 weeks. The study is registered with the Clinical Trials Registry of India (identifier number: CTRI/2019/01/017156). RESULTS: Between 23 March 2019 and 14 February 2020, 396 subjects were enrolled, with 198 patients each in the fixed-triple (GB/FF/FP) and open-triple (GB+FF/FP) groups. The difference in least-square mean (LSM) changes in pre-dose FEV1 from baseline at 12 weeks was noninferior between the groups (p<0.05). The LSM change from baseline in post-dose FEV1 was comparable (p=0.38). A superiority test showed comparable efficacy (p=0.12) for the difference in mean change from baseline in trough FEV1 between the groups. Adverse events (mild or moderate) were recorded in 25.3% and 24.9% of subjects in the GB/FF/FP and GB+FF/FP groups. CONCLUSIONS: Fixed triple therapy with GB/FF/FP provides comparable bronchodilation and lung function improvement as open-triple therapy. It is safe and well tolerated in symptomatic COPD patients with a history of exacerbations.

Fixed-dose combination of three drugs, i.e. LABA/LAMA/ICS for COPD: Results of a real-world study from India.

BACKGROUND: The use of triple therapy with inhaled corticosteroids, long-acting beta-agonist and long-acting antimuscarinics has been shown to be beneficial in COPD patients who continue to have symptoms and exacerbations, despite receiving dual bronchodilator combinations. This study assessed the real-world effectiveness and safety of once-daily, fixed-dose combination of Tiotropium/Formoterol/Ciclesonide (TFC) (18 mcg/12 mcg/400 mcg) via dry powder inhaler (DPI) or metered dose inhaler (MDI) in patients with COPD. PATIENTS AND METHODS: In this 24-week, open-label, prospective, non-comparative, multicentre, real-world study, COPD patients requiring triple therapy as judged by their physician, were enrolled. The primary endpoint was mean change from baseline in pre-dose Forced Expiratory Volume in 1 s (FEV1) at week 24. Pre and post-dose (30 min) FEV1, Forced Vital capacity (FVC), COPD Assessment Test (CAT), modified Medical Research Council (mMRC) score and safety were also evaluated. A post-hoc analysis was conducted to evaluate the efficacy of the triple drug combination among smoker and non-smoker COPD patients. RESULTS: Out of the 297 patients enrolled [mean age 61 ± 10 years; 84.8% males; 55.2% smokers and post-dose FEV1 (% predicted) 39 ± 16%], 253 completed the study. Mean change in pre-dose FEV1 from baseline to week 24 increased significantly after administering the triple drug combination [580 ± 600 mL, 95% CI (510, 650 mL), p < 0.0001]. The increase in the pre-dose FEV1 was significant at all time points (p < 0.0001). Similar improvements were seen in pre-dose FVC, post-dose FEV1 and post-dose FVC across all time points. CAT scores and the proportion of patients with improved mMRC score improved at all visits. The post-hoc analysis showed that TFC significantly increased pre-dose FEV1 both among smokers [mean change 200 ± 430 mL, 95% CI (130, 270 mL), p < 0.0001] as well as non-smokers [990 ± 470 mL, 95% CI (900, 1070 mL), p < 0.0001] at week 24. This difference was significant from week 12 onwards. Mean change in pre and post-dose FEV1 and FVC was significant across all visits between the two groups. At week 24, CAT score reduced significantly from baseline (overall: -6.6 ± 6.07; smokers: -5.17 + 6.96; non-smokers: 8.06 ± 4.44; all p < 0.0001). The mean difference between the two groups was 2.88 (p < 0.0001) at week 24. TFC was well tolerated. CONCLUSION: In this real world, multicentre study in India, TFC significantly improved lung function, symptoms and quality of life among all patients with COPD, but the effect was more pronounced among non-smoker COPD patients.

Efficacy and Safety of Remogliflozin Etabonate, a New Sodium Glucose Co-Transporter-2 Inhibitor, in Patients with Type 2 Diabetes Mellitus: A 24-Week, Randomized, Double-Blind, Active-Controlled Trial.

BACKGROUND: Metformin is the first-line treatment for type 2 diabetes mellitus (T2DM), but many patients either cannot tolerate it or cannot achieve glycemic control with metformin alone, so treatment with other glucose-lowering agents in combination with metformin is frequently required. Remogliflozin etabonate, a novel agent, is an orally bioavailable prodrug of remogliflozin, which is a potent and selective sodium-glucose co-transporter-2 inhibitor. OBJECTIVE: Our objective was to evaluate the efficacy and safety of remogliflozin etabonate compared with dapagliflozin in subjects with T2DM in whom a stable dose of metformin as monotherapy was providing inadequate glycemic control. METHODS: A 24-week randomized, double-blind, double-dummy, active-controlled, three-arm, parallel-group, multicenter, phase III study was conducted in India. Patients aged ≥ 18 and ≤ 65 years diagnosed with T2DM, receiving metformin ≥ 1500 mg/day, and with glycated hemoglobin (HbA1c) levels ≥ 7 to ≤ 10% at screening were randomized into three groups. Every patient received metformin ≥ 1500 mg and either remogliflozin etabonate 100 mg twice daily (BID) (group 1, n = 225) or remogliflozin etabonate 250 mg BID (group 2, n = 241) or dapagliflozin 10 mg once daily (QD) in the morning and placebo QD in the evening (group 3, n = 146). The patients were followed-up at weeks 1 and 4 and at 4-week intervals thereafter until week 24. The endpoints included mean change in HbA1c (primary endpoint, noninferiority margin = 0.35), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), bodyweight, blood pressure, and fasting lipids. Treatment-emergent adverse events (TEAEs), safety laboratory values, electrocardiogram, and vital signs were evaluated. RESULTS: Of 612 randomized patients, 167 (group 1), 175 (group 2), and 103 (group 3) patients with comparable baseline characteristics completed the study. Mean change ± standard error (SE) in HbA1c from baseline to week 24 was - 0.72 ± 0.09, - 0.77 ± 0.09, and - 0.58 ± 0.12% in groups 1, 2, and 3, respectively. The difference in mean HbA1c of group 1 versus group 3 (- 0.14%, 90% confidence interval [CI] - 0.38 to 0.10) and group 2 versus group 3 (- 0.19%; 90% CI - 0.42 to 0.05) was noninferior to that in group 3 (p < 0.001). No significant difference was found between group 1 or group 2 and group 3 in change in FPG, PPG, and bodyweight. The overall incidence of TEAEs was comparable across study groups (group 1 = 32.6%, group 2 = 34.4%, group 3 = 29.5%), including adverse events (AEs) of special interest (hypoglycemic events, urinary tract infection, genital fungal infection). Most TEAEs were mild to moderate in intensity, and no severe AEs were reported. CONCLUSION: This study demonstrated the noninferiority of remogliflozin etabonate 100 and 250 mg compared with dapagliflozin, from the first analysis of an initial 612 patients. Remogliflozin etabonate therefore may be considered an effective and well-tolerated alternative treatment option for glycemic control in T2DM. TRIAL REGISTRATION: CTRI/2017/07/009121.

An investigation into the stress-relieving and pharmacological actions of an ashwagandha (Withania somnifera) extract: A randomized, double-blind, placebo-controlled study.

BACKGROUND: Ashwagandha (Withania somnifera (L.) Dunal) is a herb traditionally used to reduce stress and enhance wellbeing. The aim of this study was to investigate its anxiolytic effects on adults with self-reported high stress and to examine potential mechanisms associated with its therapeutic effects. METHODS: In this 60-day, randomized, double-blind, placebo-controlled study the stress-relieving and pharmacological activity of an ashwagandha extract was investigated in stressed, healthy adults. Sixty adults were randomly allocated to take either a placebo or 240 mg of a standardized ashwagandha extract (Shoden) once daily. Outcomes were measured using the Hamilton Anxiety Rating Scale (HAM-A), Depression, Anxiety, and Stress Scale -21 (DASS-21), and hormonal changes in cortisol, dehydroepiandrosterone-sulphate (DHEA-S), and testosterone. RESULTS: All participants completed the trial with no adverse events reported. In comparison with the placebo, ashwagandha supplementation was associated with a statistically significant reduction in the HAM-A (P = .040) and a near-significant reduction in the DASS-21 (P = .096). Ashwagandha intake was also associated with greater reductions in morning cortisol (P < .001), and DHEA-S (P = .004) compared with the placebo. Testosterone levels increased in males (P = .038) but not females (P = .989) over time, although this change was not statistically significant compared with the placebo (P = .158). CONCLUSIONS: These findings suggest that ashwagandha's stress-relieving effects may occur via its moderating effect on the hypothalamus-pituitary-adrenal axis. However, further investigation utilizing larger sample sizes, diverse clinical and cultural populations, and varying treatment dosages are needed to substantiate these findings. TRIAL REGISTRATION: Clinical Trials Registry-India (CTRI registration number: CTRI/2017/08/009449; date of registration 22/08/2017).

Classification of voluntary coughs applied to the screening of respiratory disease.

Pulmonary and respiratory diseases (e.g. asthma, COPD, allergies, pneumonia, tuberculosis, etc.) represent a large proportion of the global disease burden, mortality, and disability. In this context of creating automated diagnostic tools, we explore how the analysis of voluntary cough sounds may be used to screen for pulmonary disease. As a clinical study, voluntary coughs were recorded using a custom mobile phone stethoscope from 54 patients, of which 7 had COPD, 15 had asthma, 11 had allergic rhinitis, 17 had both asthma and allergic rhinitis, and four had both COPD and allergic rhinitis. Data were also collected from 33 healthy subjects. These patients also received full auscultation at 11 sites, given a clinical questionnaire, and underwent full pulmonary function testing (spirometer, body plethysmograph, DLCO) which culminated in a diagnosis provided by an experienced pulmonologist. From machine learning analysis of these data, we show that it is possible to achieve good classification of cough sounds in terms of Wet vs Dry, yielding an ROC curve with AUC of 0.94, and show that voluntary coughs can serve as an effective test for determining Healthy vs Unhealthy (sensitivity=35.7% specificity=100%). We also show that the use of cough sounds can enhance the performance of other diagnostic tools such as a patient questionnaire and peak flow meter; however voluntary coughs alone provide relatively little value in determining specific disease diagnosis.

Peak flow meter with a questionnaire and mini-spirometer to help detect asthma and COPD in real-life clinical practice: a cross-sectional study.

Peak flow meter with questionnaire and mini-spirometer are considered as alternative tools to spirometry for screening of asthma and chronic obstructive pulmonary disease. However, the accuracy of these tools together, in clinical settings for disease diagnosis, has not been studied. Two hundred consecutive patients with respiratory complaints answered a short symptom questionnaire and performed peak expiratory flow measurements, standard spirometry with Koko spirometer and mini-spirometry (COPD-6). Spirometry was repeated after bronchodilation. Physician made a final diagnosis of asthma, chronic obstructive pulmonary disease and others. One eighty nine patients (78 females) with age 51 ± 17 years with asthma (115), chronic obstructive pulmonary disease (33) and others (41) completed the study. "Breathlessness > 6months" and "cough > 6months" were important symptoms to detect obstructive airways disease. "Asymptomatic period > 2 weeks" had the best sensitivity (Sn) and specificity (Sp) to differentiate asthma and chronic obstructive pulmonary disease. A peak expiratory flow of < 80% predicted was the best cut-off to detect airflow limitation (Sn 90%, Sp 50%). Respiratory symptoms with PEF < 80% predicted, had Sn 84 and Sp 93% to detect OAD. COPD-6 device under-estimated FEV1 by 13 mL (95% CI: -212, 185). At a cut-off of 0.75, the FEV1/FEV6 had the best accuracy (Sn 80%, Sp 86%) to detect airflow limitation. Peak flow meter with few symptom questions can be effectively used in clinical practice for objective detection of asthma and chronic obstructive pulmonary disease, in the absence of good quality spirometry. Mini-spirometers are useful in detection of obstructive airways diseases but FEV1 measured is inaccurate. CHRONIC LUNG DISEASES: DIFFERENTIATING CONDITIONS IN POORLY-EQUIPPED SETTINGS: A simple questionnaire and peak flow meter measurements can help doctors differentiate between asthma and chronic lung disease. In clinical settings where access to specialist equipment and knowledge is limited, it can be challenging for doctors to tell the difference between asthma and chronic obstructive pulmonary disease (COPD). To determine a viable alternative method for differentiating between these diseases, Rahul Kodgule and colleagues at the Chest Research Foundation in Pune, India, trialed a simplified version of two existing symptom questionnaires, combined with peak flow meter measurements. They assessed 189 patients using this method, and found it aided diagnosis with high sensitivity and specificity. Breathlessness, cough and wheeze were the minimal symptoms required for COPD diagnosis, while the length of asymptomatic periods was most helpful in distinguishing asthma from COPD.

Use of spirometry among chest physicians and primary care physicians in India.

Although spirometry is the gold-standard diagnostic test for obstructive airways diseases, it remains poorly utilised in clinical practice. We aimed to investigate the use of spirometry across India, the change in its usage over a period of time and to understand the reasons for its under-utilisation. Two nationwide surveys were conducted in the years 2005 and 2013, among four groups of doctors: chest physicians (CPs), general physicians (GenPs), general practitioners (GPs) and paediatricians (Ps). A total of 1,000 physicians from each of the four groups were randomly selected from our database in the years 2005 and 2013. These surveys were conducted in 52 cities and towns across 15 states in India. A questionnaire was administered to the physicians, which captured information about their demographic details, type of practice and use of spirometry. The overall response rates of the physicians in 2005 and 2013 were 42.8% and 54.9%, respectively. Spirometry was reported to be used by 55% CPs, 20% GenPs, 10% GPs and 5% Ps in 2005, and this increased by 30.9% among CPs (P value <0.01), 18% among GenPs (P value=0.01), 20% among GPs (P value: not significant) and 224% among Ps (P value <0.01). The reasons for not using spirometry varied between 2005 and 2013. In all, 32.2% of physicians were unaware of which predicted equation they were using. The use of spirometry in India is low, although it seems to have improved over the years. The reasons identified in this study for under-utilisation should be used to address initiatives to improve the use of spirometry in clinical practice.

A randomized, double-blind study comparing the efficacy and safety of a combination of formoterol and ciclesonide with ciclesonide alone in asthma subjects with moderate-to-severe airflow limitation.

CONTEXT: The combination of inhaled corticosteroids (ICS) and long-acting beta-agonists (LABA) is widely used in the treatment of moderate-to-severe asthma uncontrolled by ICS alone. AIMS: To evaluate the efficacy and safety of a new ICS-LABA combination inhaler containing Formoterol (F) and Ciclesonide (C). SETTINGS AND DESIGN: A double-blind, double-dummy, parallel group fashion, multi-centric study. SUBJECTS AND METHODS: A total of 169 asthma patients received Ciclesonide 80 µg once daily during a 4-week run-in period, after which, they were randomized to receive either C (80 µg) or a combination of F (4.5 µg) and C (80 µg) (FC) both delivered through a hydro-fluro-alkane pressurized-metered-dose inhaler as 1 puff twice daily, for 6 weeks. STATISTICAL ANALYSIS USED: Inter-group differences were compared using t-test for independent samples at a significance level of 5%. RESULTS: From baseline, the improvements in forced expiratory volume in 1 s at 1, 3, and 6 weeks was significantly higher in the FC group compared to Group C (110 ml vs. 40 ml, 140 ml vs. 20 ml, and 110 ml vs. 40 ml, respectively, all P < 0.05). From baseline, the improvements in mean morning peak expiratory flow at 1, 3, and 6 weeks was significantly higher in the FC group compared to Group C (17 L/min vs.-3 L/min, 22 L/min vs. 3 L/min, and 30 ml vs. 8 L/min respectively, all P < 0.05). The changes in symptom scores were similar in both the groups. The adverse events in the FC group were not significantly different from those in the C group. CONCLUSIONS: FC provides better improvement than C alone in terms of lung function and symptoms without increased risk of adverse events in asthma patients.

A mobile platform for automated screening of asthma and chronic obstructive pulmonary disease.

Chronic Obstructive Pulmonary Disease (COPD) and asthma each represent a large proportion of the global disease burden; COPD is the third leading cause of death worldwide and asthma is one of the most prevalent chronic diseases, afflicting over 300 million people. Much of this burden is concentrated in the developing world, where patients lack access to physicians trained in the diagnosis of pulmonary disease. As a result, these patients experience high rates of underdiagnosis and misdiagnosis. To address this need, we present a mobile platform capable of screening for Asthma and COPD. Our solution is based on a mobile smart phone and consists of an electronic stethoscope, a peak flow meter application, and a patient questionnaire. This data is combined with a machine learning algorithm to identify patients with asthma and COPD. To test and validate the design, we collected data from 119 healthy and sick participants using our custom mobile application and ran the analysis on a PC computer. For comparison, all subjects were examined by an experienced pulmonologist using a full pulmonary testing laboratory. Employing a two-stage logistic regression model, our algorithms were first able to identify patients with either asthma or COPD from the general population, yielding an ROC curve with an AUC of 0.95. Then, after identifying these patients, our algorithm was able to distinguish between patients with asthma and patients with COPD, yielding an ROC curve with AUC of 0.97. This work represents an important milestone towards creating a self-contained mobile phone-based platform that can be used for screening and diagnosis of pulmonary disease in many parts of the world.

Application of semi-supervised deep learning to lung sound analysis.

The analysis of lung sounds, collected through auscultation, is a fundamental component of pulmonary disease diagnostics for primary care and general patient monitoring for telemedicine. Despite advances in computation and algorithms, the goal of automated lung sound identification and classification has remained elusive. Over the past 40 years, published work in this field has demonstrated only limited success in identifying lung sounds, with most published studies using only a small numbers of patients (typically N<;20) and usually limited to a single type of lung sound. Larger research studies have also been impeded by the challenge of labeling large volumes of data, which is extremely labor-intensive. In this paper, we present the development of a semi-supervised deep learning algorithm for automatically classify lung sounds from a relatively large number of patients (N=284). Focusing on the two most common lung sounds, wheeze and crackle, we present results from 11,627 sound files recorded from 11 different auscultation locations on these 284 patients with pulmonary disease. 890 of these sound files were labeled to evaluate the model, which is significantly larger than previously published studies. Data was collected with a custom mobile phone application and a low-cost (US$30) electronic stethoscope. On this data set, our algorithm achieves ROC curves with AUCs of 0.86 for wheeze and 0.74 for crackle. Most importantly, this study demonstrates how semi-supervised deep learning can be used with larger data sets without requiring extensive labeling of data.

Priming of beta-2 agonist and antimuscarinic induced physiological responses induced by 1200mg/day NAC in moderate to severe COPD patients: A pilot study.

UNLABELLED: This study evaluated antioxidant modulations of lung physiological-responses to beta-2-agonist and antimuscarinic bronchodilators with 1200mg/day n-acetyl-cysteine (NAC) in a placebo-controlled, randomised, double-blind, parallel-group study, in moderate-very severe COPD patients. METHODS: 15 COPD patients received NAC treatment, while 9 COPD patients received placebo treatment, for 15 days. Pre-and-post salbutamol and ipratopium-bromide lung-physiology responses were measured using body-plethysmography, impulse-oscillometry (IOS) and spirometry before-and-after study treatments. RESULTS: Compared to pre-treatment, the NAC-treatment significantly enhanced the potential of ipratopium-bromide to reduce functional-residual-capacity (FRC) by nearly 3-folds (mean% FRC-response: pre-NAC: -5.51%±10.42% versus post-NAC: -17.89%±12.94%, p=0.02; mean-absolute FRC-response: pre-NAC: -300ml±450ml versus post-NAC: -770ml±550ml, p=0.02), which was superior to placebo-treatment. The increase in total-lung-capacity response to ipratopium-bromide, although insignificant, was superior with post-NAC treatment versus post-placebo treatment (p=0.049). The salbutamol-response remained unaltered with either treatment. CONCLUSION: The treatment with 1200mg/day NAC has potential to enhance the bronchodilator ability of antimuscarinic-agents but not beta-2-agonist. However, its clinical application has to be established in large sample-size studies for longer-duration.