Evolving to a single inhaler extrafine LABA/LAMA/ICS - Inhalation technique and adherence at the heart of COPD patient care (TRIVOLVE).

OBJECTIVE: Incorrect inhaler use and poor treatment adherence have a negative impact on COPD outcomes. This multi-centre, single arm, non-interventional, phase IV study investigated whether inhalation technique, treatment adherence and patient outcomes change in patients who evolve from dual therapy or multiple inhaler triple therapy to single inhaler extrafine triple therapy (beclomethasone dipropionate (BDP, 87 µg), formoterol fumarate (FF, 5 µg) and glycopyrronium (G, 9 µg)) in combination with inhalation technique training. METHODS: A total of 126 COPD patients were included in the per protocol set. Inhalation technique and treatment adherence were assessed at baseline and at two visits at approximately 3 and 6 months of treatment with extrafine BDP/FF/G. In addition, lung function, symptom score, patient satisfaction and exacerbations (exploratory) were followed up. RESULTS: Before switching to single inhaler extrafine BDP/FF/G (baseline), any device errors and critical errors were detected for 28.8% and 9.6% of patients, respectively. After switching to BDP/FF/G, the percentage of patients with any device errors decreased to 14.0% (visit 2) and 16.3% (visit 3), without critical errors at the two follow-up visits. Treatment adherence increased from 67.5% at baseline to 75.8% (visit 2) and 80% (visit 3). In addition, lung function, symptom and patient satisfaction scores improved, whilst exacerbation rates substantially decreased. CONCLUSIONS: This observational study demonstrates that in eligible COPD patients in a real-life setting, the switch from dual therapy or multiple inhaler triple therapy to single inhaler extrafine BDP/FF/G in combination with inhalation technique training is associated with improved inhalation technique and adherence.

Dual-Network Structured Nanofibrous Membranes with Superelevated Interception Probability for Extrafine Particles.

Airborne particulate matter (PM) pollution has caused a public health threat, including nanoscale particles, especially with emerging infectious diseases and indoor and vehicular environmental pollution. However, most existing indoor air filtration units are expensive, energy-intensive, and bulky, and there is an unavoidable trade-off between low-efficiency PM0.3/pathogen interception, PM removal, and air resistance. Herein, we designed and synthesized a two-dimensional continuous cellulose-sheath/net with a unique dual-network corrugated architecture to manufacture high-efficiency air filters and even N95 particulate face mask. Combined with its sheath/net structured pores (size 100-200 nm) consisting of a cellulose framework (1-100 nm diameter), the cellulose sheath/net filter offers high-efficiency air filtration (>99.5338%, Extrafine particles; >99.9999%, PM2.5), low-pressure drops, and a robustness quality factor of >0.14 Pa-1, utilizing their ultralight weight of 30 mg/m2 and physical adhesion and sieving behaviors. Simultaneously, masks prepared with cellulose-sheath/net filters are more likely to capture and block smaller particles than the N95 standard. The synthesis of such materials with their nanoscale features and designed macrostructures may suggest new design criteria for a novel generation of high-efficiency air filter media for different applications such as personal protection products and industrial dust removal.

Impulse Oscillometry, Small Airways Disease, and Extra-Fine Formulations in Asthma and Chronic Obstructive Pulmonary Disease: Windows for New Opportunities.

In recent years, the perspective of management of respiratory disease has been gradually changing in light of the increasing evidence of small airways as the major site of airflow obstruction contributing to the development of both COPD and asthma already in early stages of disease. First and foremost, the evidence is redefining disease severity, identifying small airways disease phenotypes and early signs of disease, and revising prevalence and overall epidemiological data as well. Much effort has been put toward the instrumental assessment of small airways' involvement and early detection. Several clinical trials have evaluated the advantage of extra-fine formulations which can best target the small airways in uncontrolled asthma and severe COPD. Here, we briefly present a practical overview of the role of the small airways in disease, the most appropriate diagnostic methods for quantifying their impairment, and provide some insight into the costs of respiratory management in Italy, especially in sub-optimally controlled disease.

TRICOP - A Real-world effectiveness study with a single-inhaler extrafine triple therapy over 52 weeks in Austrian patients with COPD.

OBJECTIVE: Evidence of the efficacy of single-inhaler triple therapy in COPD patients inferred from RCTs has not been assessed in a real-world setting in Austria. In this non-interventional study (NIS) tolerability and effectiveness of extrafine beclometasone-dipropionate, formoterol-fumarate and glycopyrronium (Trimbow® 87/5/9 µg) was evaluated in COPD patients. METHODS: A prospective NIS was conducted over 52 weeks in 24 sites in Austria. Eligible COPD patients had an indication for treatment with single-inhaler BDP/FF/G. In this study tolerability, lung function, exacerbation rate, symptom scores and CAT scores were recorded. RESULTS: 265 patients with moderate to very severe airflow limitation (GOLD Grade 2-4: 96.2%) and persistent symptoms (GOLD B: 62.3%, GOLD D: 34%) according to the 2018 GOLD Report were included. After 52 weeks, a significant improvement was detected in lung function (FEV1, FEV1% predicted and FVC; p < 0.001) and symptoms (cough, sputum and shortness of breath; p < 0.001). A clinically relevant improvement in CAT score observed at 12 weeks persisted after 52 weeks in GOLD B and GOLD D patients (p < 0.001), paralleled by a significant reduction of moderate and severe exacerbations by 57.4% and 27.3%, respectively (p < 0.001). After 52 weeks, 93.7% of the patients continued the treatment. Of 21 adverse events reported 16 were non-serious, five were serious, none were deemed drug related. CONCLUSIONS: The present results support the tolerability and effectiveness of extrafine BDP/FF/G in COPD patients in a real-world setting, showing an improvement in lung function, symptom control and a significant reduction in exacerbations.

Effect of extrafine formulation of BDP/FF inhaler on asthma control, small airway function and airway inflammation among Mexican asthmatic patients. A retrospective analysis.

BACKGROUND: Asthma, an inflammatory disease affecting more than 300 million patients in the world. Small airways are by far bigger than the large airway's one and constitutes the area most affected by asthma. Reaching the small airways represents a challenge for treatments because of the dimensions and structure of the bronchial lumen. Inhaled extrafine (ExF) combinations are needed to reach and treat them. This study aimed to assess the effect of extrafine Beclometasone dipropionate/Formoterol fumarate (BDP/FF) in the control of symptoms, lung function and lung inflammation in patients with asthma. METHODS: Retrospective study, carried out in 62 Mexican patients diagnosed with asthma and treated with two inhalations twice daily of ExF BDP/FF 100/6 µg (via pMDI) and with an Asthma Control Test (ACT) score ≤19 points. Moreover, from patient's files, we analysed ACT score, Impulse Oscillometry (IOS) and Fractional exhaled Nitric Oxide (FeNO) both from their first consultation (baseline) and after one month of therapy. RESULTS: BDP/FF 100/6 µg ExF showed that ACT, 79% of patients achieved control of disease (ACT ≥ 20 points) and 14.5% of patients achieved total control of the disease (ACT = 25 points); Oscillometry values R5- R20 diminished by 41%, X5 by 18.1% and AX by 56.5% and FeNO decreased by 52% after one month of treatment. CONCLUSIONS: BDP/FF 100/6 µg extrafine improved asthma control after one month of treatment, and this was sustained for 3 months. Likewise, both the lung function, measured by IOS and inflammatory state, measured by FeNO, also significantly improved.

Treatment response according to small airway phenotypes: a real-life observational study.

OBJECTIVE: Scant clinical data are available on the effects of current treatments for asthma on different subgroups of patients with this disease. We conducted a prospective, noninterventional, multicenter real-life study in adult patients with persistent asthma, and we specifically analyzed the effects of treatment with extrafine beclometasone dipropionate/formoterol (BDP/F) in asthma patients categorized by phenotypes related to small airways (i.e. smoking habits, disease duration, and air trapping). METHODS: Patients received BDP/F as a fixed combination (100/6 µg), administered in 1-2 inhalations twice daily over a period of 12 weeks. Peak expiratory flow (PEF), forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), number of asthma attacks, asthma control, and severity of asthma symptoms were evaluated in the overall population and in different subgroups at three different time points. RESULTS: Overall, 213 patients were enrolled. In the overall population the treatment resulted in a significant increase in the proportion of well controlled patients (from 6.1% to 66.3%; p<0.001), and a reduction of uncontrolled subjects (70.3% versus 10.0%; p<0.001). BDP/F was also associated with a reduction in asthma attacks and an improvement of symptoms. These results were confirmed in specific subgroups of patients identified as small airway phenotypes: smokers, elderly patients, those with long duration of disease and air trapping. CONCLUSIONS: This real-life observational study indicates that extrafine BDP/F in a fixed combination improves asthma control and symptoms in the overall population as well as specific subgroups of patients.

NEXThaler, an innovative dry powder inhaler delivering an extrafine fixed combination of beclometasone and formoterol to treat large and small airways in asthma.

INTRODUCTION: Airway inflammation and remodelling in asthma occur in the large airways and also in the small airways. The small airways are those < 2 mm in diameter and are significant sites of chronic asthmatic inflammation. It is important, therefore, to target the small as well as the large airways in any strategy for effective treatment of this disease. AREAS COVERED: The present review deals with the recently developed fixed dose drug combination of beclometasone dipropionate/formoterol fumarate that emits extrafine particles when delivered from an innovative dry powder inhaler (DPI), NEXThaler®. The aim is to present the technical and clinical aspects of aerosolized drug delivery to the lungs. EXPERT OPINION: The data show that the NEXThaler DPI is an efficient device for the management of persistent asthma. The evaluation of the inhalation profiles through the NEXThaler DPI demonstrates that device activation and consistent dose delivery occurs at patient achievable inhalation flow rates, and supports the broad utility of the NEXThaler DPI in patients with asthma. Overall, all the effectiveness, efficiency and satisfaction outcomes demonstrate the NEXThaler DPI is easy to use.