Comparison of a portable, pneumotach flow-sensor-based spirometer (Spirofy™) with the vitalograph alpha Touch™ spirometer in evaluating lung function in healthy individuals, asthmatics, and COPD patients-a randomized, crossover study.

BACKGROUND: Spirofy™ is India's first portable, pneumotach flow-sensor-based digital spirometer developed to diagnose asthma and chronic obstructive pulmonary disease (COPD). In this study, we compared the performance of the Spirofy™ device with that of the Vitalograph Alpha Touch™ spirometer in measuring the lung capacities of healthy individuals, asthmatics, and COPD patients. We also assessed the inter-device variability between two Spirofy™ devices. METHODS: In a randomized, three-way crossover, open-label study, we measured the differences in forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) between the Spirofy™ and Vitalograph Alpha Touch™ spirometers. A proportion of the FEV1/FVC ratio distribution of < 0.7 was used to compare the diagnostic accuracies of the Spirofy™ with Vitalograph™ Alpha Touch™ spirometers. RESULTS: Ninety subjects participated in this study. The mean ± SD FVC values obtained from the Spirofy™ 1, Spirofy™ 2, and Vitalograph Alpha Touch™ devices were 2.60 ± 1.05 L, 2.64 ± 1.04 L, and 2.67 ± 1.04 L, respectively. The mean ± SD FEV1 values obtained from the Spirofy™ 1, Spirofy™ 2, and Vitalograph Alpha Touch™ devices were 1.87 ± 0.92 (L), 1.88 ± 0.92 (L), and 1.93 ± 0.93 (L), respectively. A significant positive correlation was found between the FVC and FEV1 values recorded by Vitalograph Alpha Touch™, Spirofy™ 1, and Spirofy™ 2. As compared to Vitalograph Alpha Touch™, the Spirofy™ device showed good sensitivity (97%), specificity (90%), and overall accuracy (93.3%) at an FEV1/FVC ratio < 0.7. No inter-device variability was observed between the two Spirofy™ devices. CONCLUSION: Spirofy™ is a portable and easy-to-use device and is as accurate as the standard Vitalograph Alpha Touch™ spirometer for the diagnosis of COPD and asthma. TRIAL REGISTRATION: CTRI/2021/09/036492 (Clinical Trials Registry - India).

Efficacy and safety of glycopyrronium/formoterol delivered via a dry powder inhaler in patients with moderate to severe chronic obstructive pulmonary disease: Results from a multi-centre, open-label, randomised study.

Background: We designed this randomised, open-label, parallel group, multi-centre study to investigate the efficacy and safety of glycopyrronium/formoterol, a long-acting muscarinic antagonist/long-acting ß2-agonist fixed dose combination, delivered through a dry powder inhaler (DPI) in patients with chronic obstructive pulmonary disease (COPD). Material and Methods: We randomised (1:1) patients with moderate to severe COPD (N = 356) to receive glycopyrronium 25 µg/formoterol 12 µg via DPI twice daily (GF-DPI) or glycopyrronium 50 µg monotherapy via DPI once daily (G-DPI). The primary study endpoint was the mean change from the baseline in pre-dose trough-forced expiratory volume in one second (FEV1) at 12 weeks. Results: At week 12, the mean increase from the baseline in pre-dose trough FEV1 was higher in the GF-DPI group (120 ml) than in the G-DPI (60 ml) group. The mean difference (MD) between treatment groups was 0.06 L (95% CI: 0.00-0.12 L, P < 0.0001 for non-inferiority). At week 12, the mean pre-dose forced vital capacity (FVC), 1 hour post-dose FEV1, and post-dose FVC increased significantly from the baseline only in the GF-DPI group (p < 0.0001). The reduction in the COPD assessment test score was greater in the GF-DPI group (p = 0.0379). The average daily number of puffs of rescue medication and the reduction in mean modified Medical Research Council scale, COPD, and Asthma Sleep Impact Scale score at week 12 were similar between groups (p > 0.05). Overall, 35 adverse events and two serious adverse events unrelated to study drugs were reported. Both groups had similar results for overall drug safety. Conclusion: The results demonstrate efficacy and safety of GF-DPI in Indian patients with moderate to severe COPD. Treatment with GF-DPI significantly improved the lung function and quality of life and was well tolerated.

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.

Device-handling study of a novel breath-actuated inhaler, Synchrobreathe®, versus a pMDI.

INTRODUCTION: Synchrobreathe®, a new-generation, novel breath-actuated inhaler (BAI) can address the key issues arising during the use of both pressurised metered dose inhalers ([pMDIs]; hand-breath coordination) and dry powder inhalers ([DPIs]; high inspiratory flow required) with respect to optimal drug deposition. MATERIALS AND METHODS: This was an open-label, prospective, 2-week, multicentre study that assessed device handling, ease of use, errors and participant perception regarding the use of Synchrobreathe® versus a pMDI in patients with chronic obstructive pulmonary disease (COPD) (n = 162) or asthma (n = 239) and inhaler-naïve healthy volunteers (n = 59). Ability to use the device without errors at the first attempt, total number of errors before and after training, time taken to use the device correctly and total number of training sessions, and number of attempts to perform the correct technique on Day 1 and Day 14 were evaluated. Device handling and preference questionnaires were also administered on Day 14. RESULTS: Of 460 participants, 421 completed the study. The number of participants using Synchrobreathe without any error after reading the patient information leaflet (PIL) was significantly low (p < 0.05) on Day 1. On Day 14, significantly more number of participants used Synchrobreathe without any error (p < 0.001). The total number of errors before and after training with Synchrobreathe was significantly less (p < 0.001). The average time required to perform the inhalation technique correctly (p < 0.01) and the total number of attempts (P < 0.001) with Synchrobreathe were significantly lower. The average number of attempts to inhale correctly was significantly (p < 0.001) less with Synchrobreathe on Day1 and Day 14. Most participants rated Synchrobreathe as their choice of inhaler. CONCLUSION: Synchrobreathe is an easy-to-use and easy-to-handle device with significantly less number of errors, which may have positive implications for disease control in asthma and COPD.

Real-world evaluation of the clinical safety and efficacy of fluticasone/formoterol FDC via the Revolizer® in patients with persistent asthma in India.

The combination of inhaled corticosteroids (ICS) and long-acting beta2-agonists (LABAs) is widely used for the management of asthma. This prospective, open-label, non-comparative, observational, 24-week multicentre study is the first real-world study from India to compare the efficacy and safety of fixed-dose combination of fluticasone/formoterol (Maxiflo® 100/6 mcg or 250/6 mcg) capsules via the Revolizer® device in patients with persistent asthma. The primary efficacy analyses included mean change in Asthma Control Test (ACT™) at 4, 8, 16 and 24 weeks. Secondary efficacy analyses included mean change in morning and evening peak expiratory flow rate (PEFR) at the end of 4, 8, 16 and 24 weeks, number of patients having symptom-free days and nights at the end of 4, 8, 16 and 24 weeks, the number and severity of exacerbations over 24 weeks and response to the Usability Preference Satisfaction Confidence questionnaire after 1 week. Overall, 385 (of 401; 96.01%) enrolled patients completed the study. The mean change in ACT™ score was 6.7 ± 3.71 (95% CI: 6.32, 7.06; p < 0.0001) at week 24. The ACT™ score at weeks 4, 8 and 16 showed progressive and statistically significant increase from baseline. A statistically significant improvement in morning and evening PEFR at weeks 4, 8, 16 and 24 was reported. The proportion of patients experiencing symptom-free days and nights continuously increased from baseline to week 24. A good safety profile over the 24-week period was observed. The Revolizer® device was preferred by 94.26% patients over their current device. Fluticasone propionate/formoterol fumarate FDC capsules administered via a single-dose dry powder inhaler ([DPI], (Revolizer®) offers a novel, well-tolerated and effective treatment option for the long-term management of asthma.

Comparison of fluticasone/formoterol with budesonide/formoterol pMDI in adults with moderate to severe persistent asthma: Results from a 12-week randomized controlled trial.

BACKGROUND: Combination therapy of inhaled corticosteroid/long acting ß2-agonist (ICS/LABA) is the cornerstone of managing asthmatics who are uncontrolled with low-medium dose of ICS. The novel ICS/LABA combination of fluticasone propionate and formoterol (flu/form) provides potent anti-inflammatory and rapid bronchodilatory effect. This randomized, multi-centre, double-blind study compared the efficacy and safety of flu/form (125/6 mcg BD; Maxiflo®) with the well-established budesonide/formoterol combination (bud/form 200/6 mcg BD), both delivered through a pressurized metered dose inhaler (pMDI) in patients with moderate to severe persistent asthma over 12 weeks. METHODS: This study enrolled patients between 18 and 65 years. The primary end-point was to demonstrate non-inferiority for the mean change in the pre-dose morning peak expiratory flow values (PEF). The secondary end-points included lung function assessments, number of symptom-free days and nights, rescue medication use, day-and night-time symptom scores and safety evaluation. RESULTS: Two hundred and thirty-two patients were randomized to either flu/form (n = 117) or bud/form (n = 115). At the end of 12 weeks, flu/form was non-inferior to bud/form with regards to the primary end-point of morning PEF (48.07 L/min vs. 49.03 L/min, p > 0.05). These improvements were statistically significant (p < 0.0001) vs baseline. Similar improvements were observed between the two groups for secondary efficacy end-points including FEV1, symptom-free nights, rescue medication use, day-and night-time symptom scores (p > 0.05). Flu/form exhibited a safety profile comparable to that of bud/form. CONCLUSION: Fluticasone/formoterol combination administered through a pMDI is as efficacious and well-tolerated as budesonide/formoterol and offers a new therapeutic option for patients with moderate to severe persistent asthma.

The association between educational resource utilization and knowledge/self-management among patients with Type 2 Diabetes in Pune, India.

AIMS: Patients utilize a variety of sources to learn about their condition. This study assessed the association of these resources with patient knowledge, adherence, and physiologic outcomes. METHODS: Adults with Type 2 diabetes recruited at an outpatient clinic in Pune, India provided IRB-approved consent and completed surveys measuring diabetes knowledge, self-management, and educational resource utilization. Lab values were obtained from the patient's medical record. Statistical analysis was conducted in SPSS to determine the association between educational resources and outcomes. RESULTS: We enrolled 82 patients with a mean age of 58.3 years. The most commonly used resource was books/pamphlets. The use of television and books/pamphlets as sources of information was significantly associated with greater knowledge and self-management. Use of books and pamphlets and peers with diabetes was associated with lower fasting and postprandial blood glucose. Regression analyses controlling for age, gender, and years with diabetes revealed that use of newspapers and magazines, books and pamphlets, and television were predictors of overall diabetes knowledge and nutrition knowledge. The use of television as a source of information was a predictor of the hours exercised per week. CONCLUSIONS: Resources such as books and pamphlets, newspapers and magazines, and television are common ways that people with diabetes learn about their medical conditions. The use of television as a source of information predicted the greatest number of positive outcomes among patients, followed by use of books and pamphlets. These methods should be further explored in order to understand how their benefit may be maximized for patients.

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.

Regulatory Considerations for Approval of Generic Inhalation Drug Products in the US, EU, Brazil, China, and India.

This article describes regulatory approaches for approval of "generic" orally inhaled drug products (OIDPs) in the United States, European Union, Brazil, China and India. While registration of a generic OIDP in any given market may require some documentation of the formulation and device similarity to the "original" product as well as comparative testing of in vitro characteristics and in vivo performance, the specific documentation approaches, tests and acceptance criteria vary by the country. This divergence is due to several factors, including unique cultural, historical, legal and economic circumstances of each region; the diverse healthcare and regulatory systems; the different definitions of key terms such as "generic" and "reference" drug; the acknowledged absence of in vitro in vivo correlations for OIDPs; and the scientific and statistical issues related to OIDP testing (such as how best to account for the batch-to-batch variability of the Reference product, whether to use average bioequivalence or population bioequivalence in the statistical analysis of results, whether to use healthy volunteers or patients for pharmacokinetic studies, and which pharmacodynamic or clinical end-points should be used). As a result of this discrepancy, there are ample opportunities for the regulatory and scientific communities around the world to collaborate in developing more consistent, better aligned, science-based approaches. Moving in that direction will require both further research and further open discussion of the pros and cons of various approaches.

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.