Exploring quality of life and satisfaction with treatment in asthmatic patients receiving dry powder inhalers: a multinational survey.

INTRODUCTION: The quality of life (QoL) and device needs have not been characterized in asthmatic patients treated via dry powder inhalers (DPIs). The aim of this study was to assess the impact of asthma on health-related QoL, device satisfaction, and preference in adult asthmatic patients using DPI devices, and to identify any DPI-associated unmet needs. METHODS: An online survey was conducted between November and December 2019 on eligible patients from the Cint consumer panel across Europe. Newly designed, as well as validated questionnaires were used to collect data on QoL and inhaler satisfaction. RESULTS: A total of 1063 asthmatic patient took part in the survey; 66% of the patients reported medium or high impact of asthma on the overall QoL. The majority of patients (61%) reported high level of satisfaction with their current device. The patients with medium-to-high impact of asthma on QoL were significantly less likely to be satisfied with their current device (55%) than those who reported low-to-medium impact of asthma on QoL (67%; p-value < 0.001). "Higher number of available doses," "usability," "clear dose counter," and "feedback on correct inhalation" were the attributes mostly requested from a new device. The demand for user-friendly devices that provide feedback on correct drug administration was identified as an unmet need. CONCLUSIONS AND CLINICAL RELEVANCE: In asthmatic patients with medium to high impact of asthma on the overall QoL, the satisfaction with the device is highly affected.

Targeting the Small Airways with Inhaled Corticosteroid/Long-Acting Beta Agonist Dry Powder Inhalers: A Functional Respiratory Imaging Study.

Background: Peripheral deposition of inhaled medication is important as small airway disease has a key role in asthma. In this study, we compared the lung deposition at different mean flow rates of three inhaled corticosteroid (ICS)/long-acting beta2-agonist (LABA) combinations delivered by dry powder inhaler (DPI), that is, Foster NEXThaler® (extrafine formulation of beclomethasone/formoterol), Relvar Ellipta® (fluticasone furoate/vilanterol trifenatate), and Symbicort Turbohaler® (budesonide/formoterol). Materials and Methods:In vitro drug delivery parameters were applied to lung computerized tomography (CT) scans of 20 asthma patients by functional respiratory imaging (FRI). Aerosol airway deposition patterns were calculated as percentage (standard deviation) intrathoracic versus extrathoracic deposition, percentage peripheral deposition, and central-to-peripheral (C/P) ratio at different inspiratory mean flow rates. Results: At 60 and 40 L/min, intrathoracic deposition of ICS/LABA was significantly higher with NEXThaler versus Ellipta. Peripheral deposition (60 L/min) with NEXThaler was higher than Ellipta for ICS (24.7% [3.5%] vs. 5.0% [2.0%]; p < 0.001) and LABA (25.3% [3.5%] vs. 13.0% [3.0%]; p < 0.001). C/P ratio with NEXThaler was lower (indicating higher peripheral deposition) than Ellipta (ICS: 0.63 vs. 1.63; LABA: 0.63 vs. 0.99). Inspiratory flow rate did not impact lung deposition with NEXThaler or Ellipta. In contrast, Turbohaler performance was negatively impacted by decreasing inspiratory flow rate. In fact, although lung deposition with Turbohaler was similar to that of NEXThaler at 60 L/min, lung deposition with Turbohaler was significantly lower than NEXThaler at both 40 L/min (∼30%) and 30 L/min (∼50%). Conclusions: Using FRI, we demonstrated better peripheral deposition and C/P ratios of ICS/LABA with NEXThaler versus Ellipta. NEXThaler demonstrated inspiratory flow rate independency of lung deposition versus Turbohaler. These findings suggest that the extrafine formulation is superior to large particle formulations in delivering ICS/LABA consistently both to the large and small airways.

Inspiratory flow profile and usability of the NEXThaler, a multidose dry powder inhaler, in asthma and COPD.

BACKGROUND: Inhaler selection is important when managing respiratory conditions; a patient's inhalation technique should be appropriate for the selected device, and patients should ideally be able to use a device successfully regardless of disease severity. The NEXThaler is a multidose dry-powder inhaler with a breath-actuated mechanism (BAM) and dose counter that activates only following inhalation, so effectively an 'inhalation counter'. We assessed inspiratory flow through the NEXThaler in two studies and examined whether inhalation triggered the BAM. METHODS: The two studies were open-label, single-arm, and single visit. One study recruited patients with asthma aged ≥ 18 years; the other recruited patients with chronic obstructive pulmonary disease (COPD) aged ≥ 40 years. All patients inhaled twice through a placebo NEXThaler. The inspiratory profile through the device was assessed for each inhalation using acoustic monitoring, with flow at and time to BAM firing, peak inspiratory flow (PIF), and total inhalation time assessed. RESULTS: A total of 40 patients were enrolled in the asthma study: 20 with controlled asthma and 20 with partly controlled/uncontrolled asthma. All patients were able to trigger the BAM, as evidenced by the inhalation counter activating on closing the device. Mean flow at BAM firing following first inhalation was 35.0 (range 16.3-52.3) L/min; mean PIF was 64.6 (35.0-123.9) L/min. A total of 72 patients were enrolled in the COPD study, with data analysed for 69 (mean forced expiratory volume in 1 s 48.7% predicted [17-92%]). As with the asthma study, all patients, regardless of airflow limitation, were able to trigger the BAM. Mean flow at BAM firing following first inhalation was 41.9 (26.6-57.1) L/min; mean PIF was 68.0 (31.5-125.4) L/min. Device usability was rated highly in both studies, with 5 min sufficient to train the patients, and a click heard shortly after inhalation in all cases (providing feedback on BAM firing). CONCLUSIONS: Inhalation flows triggering the BAM in the NEXThaler were similar between patients with controlled and partly controlled/uncontrolled asthma, and were similar across COPD airflow limitation. All enrolled patients were able to activate the device.

Determinants and impact of suboptimal asthma control in Europe: The INTERNATIONAL CROSS-SECTIONAL AND LONGITUDINAL ASSESSMENT ON ASTHMA CONTROL (LIAISON) study.

BACKGROUND: According to the Global Initiative of Asthma, the aim of asthma treatment is to gain and maintain control. In the INTERNATIONAL CROSS-SECTIONAL AND LONGITUDINAL ASSESSMENT ON ASTHMA CONTROL (LIAISON) study, we evaluated the level of asthma control and quality of life (QoL), as well as their determinants and impact in a population consulting specialist settings. METHODS: LIAISON is a prospective, multicentre, observational study with a cross-sectional and a 12-month longitudinal phase. Adults with an asthma diagnosis since at least 6 months, receiving the same asthma treatment in the 4 weeks before enrolment were included. Asthma control was assessed with the 6-item Asthma Control Questionnaire (ACQ) and QoL with the MiniAsthma Quality of Life Questionnaire (MiniAQLQ). RESULTS: Overall, 8111 asthmatic patients were enrolled in 12 European countries. Asthma control was suboptimal in 56.5 % of patients and it was associated with poorer asthma-related QoL, higher risk of exacerbations and greater consumption of healthcare resources. Variables associated with suboptimal control were age, gender, obesity, smoking and comorbidities. Major determinants of poor asthma control were seasonal worsening and persisting exposure to allergens/irritants/triggers, followed by treatment-related issues. CONCLUSIONS: The cross-sectional phase results confirm that suboptimal control is frequent and has a high individual and economic impact. TRIAL REGISTRATION: The clinicaltrials.gov identifier is NCT01567280 .

Extrafine beclomethasone/formoterol compared to fluticasone/salmeterol combination therapy in COPD.

BACKGROUND: The study evaluated the efficacy of beclomethasone dipropionate/formoterol fumarate (BDP/FF) extrafine combination versus fluticasone propionate/salmeterol (FP/S) combination in COPD patients. METHODS: The trial was a 12-week multicentre, randomised, double-blind, double dummy study; 419 patients with moderate/severe COPD were randomised to BDP/FF 200/12 µg or FP/S 500/50 µg twice daily. The primary objective was to demonstrate the equivalence between treatments in terms of Transition Dyspnoea Index (TDI) score and the superiority of BDP/FF in terms of change from pre-dose in the first 30 minutes in forced expiratory volume in the first second (FEV1). Secondary endpoints included lung function, symptom scores, symptom-free days and use of rescue medication, St. George's Respiratory Questionnaire, six minute walking test and COPD exacerbations. RESULTS: BDP/FF was equivalent to FP/S in terms of TDI score and superior in terms of FEV1 change from pre-dose (p < 0.001). There were no significant differences between treatments in secondary outcome measures, confirming overall comparability in terms of efficacy and tolerability. Moreover, a clinically relevant improvement (>4 units) in SGRQ was detected in the BDP/FF group only. CONCLUSION: BDP/FF extrafine combination provides COPD patients with an equivalent improvement of dyspnoea and a faster bronchodilation in comparison to FP/S. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01245569.

Stepping-across controlled asthmatic patients to extrafine beclometasone/formoterol combination.

BACKGROUND: Asthma management focuses on achieving and maintaining asthma control. Few studies have assessed whether complete and sustained asthma control is maintained in clinical practice after stepping-across ICS/LABA fixed combinations. Aim of this double-blind, double-dummy, randomized, parallel group, controlled study was to demonstrate clinical equivalence between equipotent doses of extrafine beclometasone/formoterol (BDP/F) pMDI and fluticasone/salmeterol (FP/S) Diskus® in maintaining lung function and asthma control. METHODS: A total of 416 asthmatic patients already controlled with FP/S 500/100 µg/day (Diskus®, pMDI or separate inhalers) were randomized to a 12-week treatment with extrafine BDP/F 400/24 µg/day pMDI or FP/S 500/100 µg/day Diskus®. Pre-dose 1-s forced expiratory volume (FEV(1)) was the primary efficacy variable; secondary variables included asthma control questionnaire (ACQ-7) and FEV(1)0-1 h area under the curve (FEV(1)AUC(0-1h)). Safety was assessed through adverse events monitoring and vital signs. RESULTS: After 12 weeks of treatment, pre-dose FEV(1) did not differ between treatments (difference between means 0.01 L; 95% CI -0.03-0.06 L) with no significant changes from baseline in both groups (p = 0.726 and p = 0.783 in BDF/F arm and FP/S, respectively). ACQ-7 score showed that control was maintained after stepping-across to extrafine BDP/F. FEV(1)AUC(0-1h) was significantly higher in BDP/F arm at the beginning (p = 0.004) and at the end of the 12-week treatment period (p = 0.019). No safety issues were reported in both groups. CONCLUSIONS: Patients previously controlled with FP/S in any device formulation can effectively step-across to extrafine BDP/F pMDI, maintaining lung function and asthma control with a 5-min onset of action.

Single and multiple ascending dose studies of a novel tissue-selective oestrogen receptor modulator, CHF 4227, in healthy postmenopausal women.

AIMS: We evaluated the tolerability, adverse events profile, pharmacokinetics, and pharmacodynamics of CHF 4227, a new selective oestrogen receptor modulator (SERM), in healthy postmenopausal women. METHODS: Two phase I studies were conducted according to a double-bind, placebo-controlled design. Subjects were randomized to receive six single (5-400 mg) or five multiple oral doses of CHF 4227 for 28 days (5-100 mg). RESULTS: No vaginal bleeding and no changes in either endometrial thickness or the placenta protein 14 marker were found after 4 weeks of treatment. The compound did not induce negative effects on the fibrinolytic system. After 28 days of treatment, CHF 4227 decreased both total and LDL cholesterol concentrations (maximum decreases from baseline of 17.4% (95% CI 7.0, 27.7) and 27.6% (95% CI 9.0, 46.3), respectively). Decreases in both serum and urinary type-I C-terminal collagen telopeptide were also observed producing maximum changes of 40.6% (95% CI 29.5, 51.7), and 41.7% (95% CI 20.3, 56.8), respectively. CHF4227 (5 and 10 mg) induced near maximal oestrogen-like effects on bone markers and serum lipids without causing hot flushes. The pharmacokinetics of CHF 4227 were characterized by a slow absorption, a long elimination half-life (31-42 h after single administration) and dose linearity with respect to C(max) and AUC up to 100 mg. CONCLUSIONS: CHF 4227 is a well-tolerated SERM when administered once daily for 28 days. It is potentially active on bone resorption and serum lipids, without affecting the endometrium and without worsening hot flushes. CHF 4227 is a promising agent for the treatment of several conditions in postmenopausal women.