Breath-actuated Inhaler Research Articles

Inhaled levodopa for threatening impending OFF episodes in managing Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder that leads to the degeneration of dopaminergic neurons resulting in a widespread pathology of motor and non-motor symptoms. Oral levodopa remains the most effective symptomatic treatment of PD, but motor complications such as Off episodes occur over time. The spectrum of manifestation of OFF episodes varies, e.g., early morning akinesia, end-of-dose wearing OFF, delayed ON, suboptimal ON and dose failure. The functional disability substantially impacts the quality of life for PD patients. An innovative on-demand therapy to treat Off episodes was approved for patients receiving oral levodopa/dopa deacarboxylase inhibitor: inhaled levodopa powder (Inbrija®). The pulmonary delivery of inhaled levodopa powder provides a predictable and fast treatment effect, independent of gastrointestinal dysfunctions or food intake, which could affect levodopa absorption. Levodopa is administered with a breath-actuated inhaler device and the approved dose is 84mg per Off episode. During the pivotal SPAN-PD phase III trial, significant improvement in Unified Parkinson Disease Rating Scale III score was measured 30min post-dose at week 12. Improvement was already seen for the first measured time point 10min post-dose. No differences in pulmonary function was observed when using inhaled levodopa powder regularly for up to 12months. Inhaled levodopa powder was also approved for early morning Off episodes. The aim of this review article is to give an overview of the different clinical studies of the innovative inhaled levodopa powder, a new on-demand therapy to treat Off episodes in PD.

Pharmacokinetic and Pharmacodynamic Comparison of Fluticasone Propionate/Formoterol Fumarate Administered via a Pressurized Metered-Dose Inhaler and a Novel Breath-Actuated Inhaler in Healthy Volunteers.

Introduction: Fluticasone propionate/formoterol fumarate (fluticasone/formoterol) exposures, following administration of Flutiform® K-haler®, a breath-actuated inhaler (BAI), were compared with the Flutiform pressurized metered-dose inhaler (pMDI) with/without spacer in two healthy volunteer studies. In addition, formoterol-induced systemic pharmacodynamic (PD) effects were examined in the second study. Methods: Study 1: single-dose, three-period, crossover pharmacokinetic (PK) study with oral charcoal administration. Fluticasone/formoterol 250/10 μg was administered via BAI, pMDI, or pMDI with spacer (pMDI+S). Pulmonary exposure for BAI was deemed no less than for pMDI (primary comparator) if the lower limit of 94.12% confidence intervals (CIs) for BAI:pMDI maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUCt) ratios was ≥80%. Study 2: two-stage adaptive design, both stages being single-dose, crossover without charcoal administration. The PK stage compared fluticasone/formoterol 250/10 μg via BAI, pMDI, or pMDI+S. The primary comparisons were as follows: BAI versus pMDI+S for fluticasone and BAI versus pMDI for formoterol. Systemic safety with BAI was deemed no worse than primary comparator if the upper limit of 94.12% CIs for Cmax and AUCt ratios was ≤125%. PD assessment was to be conducted if BAI safety was not confirmed in the PK stage. Based on PK results, only formoterol PD effects were evaluated. The PD stage compared fluticasone/formoterol 1500/60 μg via BAI, pMDI, or pMDI+S; fluticasone/formoterol 500/20 μg pMDI; and formoterol 60 μg pMDI. The primary endpoint was maximum reduction in serum potassium within 4 hours postdose. Equivalence was defined as 95% CIs for BAI versus pMDI+S and pMDI ratios within 0.5-2.0. Results: Study 1: lower limit of 94.12% CIs for BAI:pMDI ratios >80%. Study 2, PK stage: upper limit of 94.12% CIs for fluticasone (BAI:pMDI+S) ratios <125%; upper limit of 94.12% CIs for formoterol (BAI:pMDI) ratios >125% (for Cmax, not AUCt). Study 2, PD stage: 95% CIs for serum potassium ratios 0.7-1.3 (BAI:pMDI+S) and 0.4-1.5 (BAI:pMDI). Conclusions: Fluticasone/formoterol BAI performance was within the range observed for the pMDI with/without a spacer. Sponsor: Mundipharma Research Ltd. EudraCT 2012-003728-19 (Study 1) and 2013-000045-39 (Study 2).

The Clinical Development of Levodopa Inhalation Powder.

Oral levodopa is the most effective treatment for Parkinson disease, but OFF periods emerge over time. Gastrointestinal dysfunction and food effects impact levodopa absorption, contributing to unpredictable control of OFF periods. Inhaled levodopa powder (Inbrija) is approved for on-demand treatment of OFF periods in patients receiving oral levodopa-dopa decarboxylase inhibitors. The 84-mg dose is administered via a breath-actuated inhaler. It provides pulmonary delivery of levodopa to the systemic circulation and is taken when a patient has an OFF period in between doses of regular oral levodopa medication. The pivotal SPAN-PD trial in patients experiencing OFF periods on oral dopaminergic therapy showed that levodopa inhalation powder 84 mg produced significant improvement in Unified Parkinson Disease Rating Scale Part III score, as measured 30 minutes postdose at week 12, and improvement was seen as early as 10 minutes. More patients in the levodopa inhalation powder group turned ON within 60 minutes of treatment and remained ON at 60 minutes than in the placebo group. Levodopa inhalation powder can also be used to treat early-morning OFF periods and, when used for up to 12 months, produced no clinically significant differences in pulmonary function compared with an untreated cohort. Levodopa inhalation powder 84 mg increased plasma levodopa concentration rapidly and with less variability than oral levodopa/carbidopa (25/100 mg). Most common adverse event associated with levodopa inhalation powder is cough, found in ~15% of patients in the SPAN-PD trial; otherwise, reported adverse events were consistent with those known to be associated with oral levodopa.

Breath-actuated INhalation TheRapy: survey of phySicians’ PErCepTion (INTROSPECT) in Nepal

Objective Breath-actuated inhalers (BAIs) are gaining attention in the management of obstructive airway diseases (OADs). In Nepal, a BAI containing fluticasone propionate/salmeterol (FPS) has been available for a year. This survey is aimed at determining the perception and experience of physicians in Nepal concerning BAIs. Methods A cross-sectional, questionnaire-based survey was conducted. A total of 141 physicians participated and filled the survey. Results Most physicians felt that the right device should be easy to teach, learn and remember. They considered coordination and multiple steps as the primary challenges with pressurized metered-dose inhalers and dry powder inhalers, respectively. Most of them agreed that BAIs could address these challenges. BAIs were not only preferred by most of the physicians for asthma and chronic obstructive pulmonary disease but were also the preferred choice in newly diagnosed patients. Physicians believed that if current patients were shifted to BAIs, it could improve inhalation technique (88%) and compliance/adherence (81%). Almost all of them (92–97%) agreed that teaching the breathing technique and the cleaning process was easier and faster in BAIs. BAIs were considered easy and simple to use. Also, BAI’s dose-counter helps patients to increase adherence to inhalation therapy. Conclusions In this INTROSPECT survey, physicians in Nepal believed that BAIs could address the key challenges faced with using pMDIs and DPIs in asthma and COPD patients.

Ефективність різних засобів доставки інгаляційних препаратів у дітей із бронхіальною астмою

Мета дослідження — оцінити ефективність техніки інгаляції при використанні різних видів інгаляторів. Матеріали та методи. 45 пацієнтам 6–17 років була проведена оцінка правильності виконання інгаляції за допомогою апарата імітації внутрішнього опору деяких видів інгаляторів та виміру швидкості, з якою відбувається вдих (In-Check-Dial). Вивчена частота помилок у різних вікових групах. Результати. 80 % дітей молодшої групи помилилися при використанні турбухалеру, 73,3 % — дозованого аерозольного інгалятора, 60 % — ізихалеру. Жоден пацієнт 6–7 років не зробив помилку при використанні дискхалеру. 100 % дітей 12–14 років зробили помилки при застосуванні дозованого аерозольного інгалятора. При використанні ізихалеру частота помилок становила 66,6 %, дискхалеру — 26,6 %. Серед дітей старшого віку частота помилок при застосуванні турбухалеру була вірогідно меншою, а саме: 40 % — у дітей 12–14 років, 25 % — 15–17 років (р &lt; 0,05). Діти 15–17 років найбільш правильно використовували турбухалер та дискхалер (помилки в 33,3 та 46,6 % відповідно). Тоді як за допомогою дозованого аерозольного інгалятора жоден пацієнт не зробив правильну інгаляцію, 93,3 % хворих також помилились у використанні інгаляції через ізихалер. Висновки. Частота помилок залежно від віку та виду інгалятора сягає 26–100 %. Найменша кількість помилок спостерігається при застосуванні дискхалеру (у всіх вікових групах), найвища — дозованого аерозольного інгалятора. З метою вибору оптимального інгалятора для дитини з бронхіальною астмою доцільно вимірювати інспіраторний потік за допомогою In-Check-Dial перед призначенням терапії.

Multidisciplinary consensus on inhaled therapy in asthma

ABSTRACT Background Asthma is managed by health professionals from different specialties. We aim to reach a consensus on the optimal use of inhaled therapy and the initial steps of asthma treatment, taking into account the opinions of the involved specialists. Methods A modified Delphi approach was used. A scientific committee provided 52 controversial statements, which were submitted to primary care physicians, allergists, and pulmonologists. Discrepancies among specialties were evaluated. Results A total of 209 specialists completed the questionnaire (20.2 ± 9.3 years of asthma management experience). A consensus was reached on 37 statements (71.1%), discrepancies among specialties were found in 14. The most recommended maintenance treatment for mild persistent asthma in adults/adolescents was low-dose-inhaled corticosteroids daily. MART (Maintenance and Reliever Therapy) was recommended as salvage treatment for moderate persistent asthma. Panelists agreed on the most frequent critical errors with pressurized Metered-Dose Inhalers or Dry-Powder Inhalers, and considered that Breath-Actuated Inhalers are a suitable option for all patients with the ability to inhale voluntarily. Conclusions The experts endorse the main guidelines recommendations; however, do not fully agree on recent GINA recommendations about the treatment of the initial steps of the disease. The experts value positively the differential characteristics of BAI over other devices.

Levodopa Inhalation Powder: A Review in Parkinson's Disease.

Levodopa inhalation powder (Inbrija®) is approved for the intermittent treatment of OFF episodes in patients with Parkinson's disease (PD) treated with levodopa/dopa-decarboxylase inhibitor (LD-DCI) in the EU and specifically with carbidopa/levodopa in the USA. The approved dosage is 84mg taken as needed up to five times a day. Administered via a breath-actuated inhaler, this formulation enables levodopa to bypass the gastrointestinal (GI) tract and, instead, rapidly enter the bloodstream through the pulmonary system. In the 12-week, double-blind, placebo-controlled, phaseIII SPAN-PD trial, as-needed levodopa inhalation powder 84mg improved motor symptoms during OFF periods in PD patients (aged 30-86years) treated with levodopa and carbidopa or benserazide. The likelihood of achieving an ON state 60min postdose was significantly higher in the levodopa inhalation powder than the placebo group, with most patients in the levodopa inhalation powder group experiencing improvements in PD symptoms. Findings from longer-term, 52-week phaseIII studies were consistent with those from the SPAN-PD trial with regards to the treatment of OFF episodes. Levodopa inhalation powder was generally well tolerated and did not noticeably affect pulmonary function in PD patients. Providing a nonintrusive, convenient treatment method, levodopa inhalation powder is a promising option for the intermittent treatment of OFF episodes in patients with PD treated with a LD-DCI.

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

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. 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. 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. 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.

Device mechanics and evaluation of inspiratory flow rate required of the beclomethasone dipropionate breath-actuated inhaler.

Background: Approximately 80% of patients with asthma and chronic obstructive pulmonary disease incorrectly use a metered-dose inhaler and, therefore, fail to obtain full benefit from their inhaler medication. Beclomethasone dipropionate (BDP) hydrofluoroalkane, an inhalation aerosol administered via a breath-actuated inhaler (BAI) has been designed to improve ease of use over press-and-breathe metered-dose inhalers by eliminating the need for hand-breath coordination. Objective: To present the mechanics of the BAI device, assess the minimum reliable inspiratory flow rate required to trigger an actuation, and evaluate if intended users can safely and effectively use the BDP BAI according to the instructions for use (IFU). Methods: Six random batches (three batches each of 40 μg and 80 μg) of 10 inhalers were evaluated for the minimum inspiratory flow rate required for actuation trigger. Each inhaler was tested for actuation at five flow rates: 12, 14, 16, 18, and 20 L/min. Simulated-use testing was conducted with 91 participants from six representative user groups in the United States to assess the use of a placebo-filled production-equivalent BDP BAI according to the IFU. Results: Across the 40-μg batches, 83% of the devices actuated at 16 L/min and 100% actuated at 18 and 20 L/min. For the 80-μg batches, 67% and 100% actuated at 18 L/min and 20 L/min, respectively. All the participants demonstrated successful use of the BDP BAI during the study session. Isolated safety-critical errors with the potential for no-dose delivery were recorded for 15 participants but were considered unrelated to the design of the IFU. Conclusion: The BDP BAI consistently triggered actuation at an airflow rate of 20 L/min and was successfully used based on guidance from the IFU only. This device provides an alternative for patients who find it difficult to use metered-dose inhaler devices correctly.

Relationship between handheld and clinic-based spirometry measurements in asthma patients receiving beclomethasone.

Handheld spirometers for home use by patients allow longitudinal spirometry data to be collected daily and may overcome some of the limitations of in-clinic spirometry (long intervals between measurements, results can be affected by site-based coaching and patient's asthma status during a given visit). To determine the relationship between spirometry values measured by clinic-based and handheld spirometers during a clinical trial. A post hoc correlation analysis of data from a 6-week phase 3 study of beclomethasone dipropionate (BDP; delivered by breath-actuated inhaler: BAI) versus placebo in patients aged ≥12 years with persistent asthma. During the study, forced expiratory volume in 1 s (FEV1) was assessed by both office-based spirometry at Weeks 2, 4 and 6, and daily by handheld spirometer as a secondary study endpoint. There was a high correlation between FEV1 values measured at home and in-clinic (overall correlation coefficient = 0.8393, R = 0.81921, 0.85927, 0.85369 and 0.83734 for BAI 320 μg/day, BAI 640 μg/day, BDP metered dose inhaler 320 μg/day and placebo treatment groups, respectively), with the scatterplot showing an upward trend for all treatment groups. Nearly all patients achieved home FEV1 values close to clinic FEV1 values, with very few outliers. Clinic-based and handheld spirometry demonstrated comparable treatment effects relative to placebo, suggesting that home spirometry could be used to help patients monitor their asthma severity. Daily measurement of FEV1 provides more comprehensive data than can be achieved through clinic visits, and may lead to a new approach to clinical trial design.

BECLOMETHASONE DIPROPIONATE DELIVERED VIA BREATH-ACTUATED INHALER IN PERSISTENT ASTHMA: EFFICACY EVALUATION ACCORDING TO PRIOR TREATMENT

Introduction The treatment effect of beclomethasone dipropionate (BDP) delivered via a novel breath-actuated inhaler (BAI) was evaluated overall, and also according to pre-study therapy to see if the latter influenced efficacy. Methods This was a Phase 3, 6-week, double-blind, placebo-controlled study (NCT02513160) in 425 patients ≥12 years with persistent asthma previously treated with non-corticosteroids (NCS), inhaled corticosteroids (ICS), or ICS/long-acting beta-2 agonists. After a washout/inhaler training period, randomized patients received placebo (BAI), placebo metered-dose inhaler (MDI), BAI 320 mcg/day, BAI 640 mcg/day, or BDP MDI 320 mcg/day. Rescue medication (albuterol/salbutamol) MDI or equivalent was permitted throughout the study. Results In 425 patients, BDP BAI 320 and 640 mcg/day significantly improved baseline-adjusted trough morning forced expiratory volume in 1 second area under the effect curve from 0 to 6 weeks (FEV1AUEC0–6wk; p Conclusions Both BDP BAI doses demonstrated significant improvements in lung function overall according to the primary study endpoint; exploratory subanalysis suggests that efficacy is independent of prior asthma therapy. The safety profile of this new BDP BAI device was comparable to the established safety profile of BDP MDI, with no new safety signals.

Randomized trial to assess the efficacy and safety of beclomethasone dipropionate breath-actuated inhaler in patients with asthma

Randomized trial to assess the efficacy and safety of beclomethasone dipropionate breath-actuated inhaler in patients with asthma

Pharmacokinetics of Beclomethasone Dipropionate Delivered by Breath-Actuated Inhaler and Metered-Dose Inhaler in Healthy Subjects.

Breath-actuated inhalers (BAIs) eliminate the need for hand-breath coordination required of pressurized metered-dose inhalers (MDIs). This pharmacokinetic study compared systemic exposure following beclomethasone dipropionate delivery through BAI versus MDI. This open-label, three-period crossover, single-dose study randomized healthy subjects aged 18-45 years (N = 72) to 1 of 6 treatment sequences containing beclomethasone dipropionate BAI 160 mcg (40 mcg/inhalation, 4 inhalations), beclomethasone dipropionate BAI 320 mcg (80 mcg/inhalation, 4 inhalations), and beclomethasone dipropionate MDI 320 mcg (80 mcg/inhalation, 4 inhalations). Blood samples were collected predose through 24 hours postdose for determination of plasma concentrations of beclomethasone-17-monopropionate (17-BMP), the active metabolite of beclomethasone dipropionate. The primary pharmacokinetic parameters were area under the plasma drug concentration-time curve (AUC) from time 0 (predose) until the last measurable drug concentration (AUC0-t) and maximum plasma drug concentration (Cmax) for 17-BMP. Safety was assessed by adverse events, vital signs, clinical laboratory tests, and physical examinations. Plasma concentrations of 17-BMP peaked at a median of 10 minutes after the last inhalation of all study treatments and remained measurable for at least 18 hours in most subjects. Mean elimination half-life was ∼4 hours. The AUC0-t and Cmax for 17-BMP were 11% and 14% higher, respectively, when beclomethasone dipropionate 320 mcg was administered through BAI versus MDI, but the 90% confidence intervals of the geometric least squares mean BAI:MDI ratio for each parameter were fully contained within the bioequivalence boundaries of 0.80-1.25. Plasma concentrations of 17-BMP following beclomethasone dipropionate 160 mcg BAI were approximately half those with 320 mcg through BAI or MDI. All treatments were safe and generally well tolerated. Systemic availability of 17-BMP following administration of beclomethasone dipropionate was bioequivalent between BAI and MDI at the 320-mcg dose, and approximately dose proportional at the 160- and 320-mcg doses using the BAI.

The Efficacy and Safety of Beclomethasone Dipropionate Delivered via a Breath-Actuated Inhaler in Adult and Adolescent Patients With Persistent Asthma

The Efficacy and Safety of Beclomethasone Dipropionate Delivered via a Breath-Actuated Inhaler in Adult and Adolescent Patients With Persistent Asthma

Guiding Inspiratory Flow: Development of the In-Check DIAL G16, a Tool for Improving Inhaler Technique.

Portable inhalers are divisible into those that deliver medication by patient triggering (pMDIs: a gentle slow inhalation) and those that use the patient's inspiratory effort as the force for deaggregation and delivery (DPIs: a stronger deeper inspiratory effort). Patient confusion and poor technique are commonplace. The use of training tools has become standard practice, and unique amongst these is an inspiratory flow meter (In-Check) which is able to simulate the resistance characteristics of different inhalers and, thereby, guide the patient to the correct effort. In-Check's origins lie in the 1960s peak expiratory flow meters, the development of the Mini-Wright peak flow meter, and inspiratory flow assessment via the nose during the 1970s–1980s. The current device (In-Check DIAL G16) is the third iteration of the original 1998 training tool, with detailed and ongoing assessments of all common inhaler resistances (including combination and breath-actuated inhaler types) summarised into resistance ranges that are preset within the device. The device works by interpolating one of six ranges with the inspiratory effort. Use of the tool has been shown to be contributory to significant improvements in asthma care and control, and it is being advocated for assessment and training in irreversible lung disease.

P143 Beclomethasone dipropionate pharmacokinetics delivered by breath-actuated inhaler and metered-dose inhaler in healthy subjects

The relative rate and extent of systemic availability of beclomethasone-17-monopropionate (17-BMP; active metabolite of beclomethasone dipropionate) delivered via a BAI and MDI were compared.

P150 Evaluation of beclomethasone dipropionate (80 and 160 mcg/day) DELIVERED via breath-actuated inhaler for persistent asthma

P150 Evaluation of beclomethasone dipropionate (80 and 160 mcg/day) DELIVERED via breath-actuated inhaler for persistent asthma

A systematic review of comparative studies of tiotropium Respimat® and tiotropium HandiHaler® in patients with chronic obstructive pulmonary disease: does inhaler choice matter?

BackgroundIn many countries worldwide, the long-acting anticholinergic drug tiotropium is available as a dry powder formulation delivered by means of the HandiHaler® inhalation device and as an aqueous solution delivered via the Respimat® Soft Mist™ Inhaler. Tiotropium HandiHaler® is a single-dose, dry powder, breath-actuated inhaler that provides delivered doses and lung deposition of tiotropium that are, over a wide range, not influenced by the severity of chronic obstructive pulmonary disease (COPD). Tiotropium Respimat® is a propellant-free, multi-dose inhaler that delivers a metered dose of medication as a fine, slow-moving, long-lasting soft mist, independently of patient inspiratory effort. The high fine-particle fraction of droplets produced by the Respimat® inhaler optimizes the efficiency of drug delivery to the lungs.MethodsTo help inform the choice of tiotropium inhaler for prescribers and patients, this systematic review summarizes the available pharmacokinetic, efficacy and safety data from comparative studies of tiotropium Respimat® and tiotropium HandiHaler® in COPD, focusing on the licensed once-daily doses of 5 and 18 μg, respectively. Data sources reviewed include publications and abstracts identified from database searches.ResultsPublished evidence from comparative studies suggests that tiotropium Respimat® 5 μg and tiotropium HandiHaler® 18 μg provide similar clinical outcomes in patients with COPD.ConclusionsThe findings indicate that physicians can base their decision about an inhaler for tiotropium on factors other than efficacy or safety. These could be patient preference for a particular inhaler, ease of use and the efficiency of drug delivery, with the aim of optimizing adherence and clinical outcomes with long-term tiotropium maintenance therapy. Video (MP4 314368 kb) Electronic supplementary materialThe online version of this article (doi:10.1186/s12890-016-0291-4) contains supplementary material, which is available to authorized users.

Ciprofloxacin dry powder for inhalation in non-cystic fibrosis bronchiectasis

ABSTRACTIntroduction: Non-cystic fibrosis bronchiectasis (NCFB) is an increasingly prevalent chronic respiratory disease, characterized by a cycle of infection and inflammation. It is progressive and associated with poor quality of life, increasing healthcare costs and mortality. Inhaled antibiotics offer the potential to decrease long-term bacterial burden and reduce or delay exacerbations which are a key driver of disease progression and healthcare costs. Currently however, no inhaled treatments are approved for the prevention of exacerbations in patients with NCFB.Areas covered: We consider current evidence for inhaled treatment in NCFB and discuss ciprofloxacin dry powder for inhalation (DPI), a novel treatment using PulmoSphere™ technology, delivered via a pocket-sized, breath-actuated inhaler. We also detail the unique features of the ongoing Phase 3 RESPIRE trials for ciprofloxacin DPI.Expert opinion: The simplicity of use and short administration time could make ciprofloxacin DPI an attractive treatment option with potential to reduce the number of exacerbations in patients with NCFB. The RESPIRE studies are the largest carried out in NCFB to date and will provide a benchmark for future trial design. If approved, following successful Phase 3 data, ciprofloxacin DPI has potential for significant use in NCFB due to its good tolerability and low treatment burden.

Salmeterol/fluticasone through breath-actuated inhaler versus pMDI: a randomized, double-blind, 12 weeks study

Objective: Salmeterol/fluticasone combination (SFC) formulated in a breath-actuated inhaler (BAI) overcomes the co-ordination problem associated with the pressurized-metered dose inhaler (pMDIs). Our aim was to compare the efficacy and the safety of SFC given through the BAI versus the conventional pMDI in moderate-to-severe asthmatics. Methods: In this randomized, double-blind, double-dummy, prospective, active-controlled, parallel group, multicenter, 12 weeks study, 150 asthmatics were randomized to receive SFC (25/125 mcg) through either BAI or pMDI. The primary efficacy endpoint was mean change in pre-dose morning PEFR value at 12 weeks and the secondary efficacy endpoints included, mean change in FEV1, pre-bronchodilator FVC, pre-dose morning and evening PEFR, symptom scores at 2, 4, 8, and 12 weeks. Patient preferences for device and safety were also assessed. Results: At 12 weeks, the mean change in pre-dose morning PEFR in BAI and pMDI groups was 50.72 L/min and 48.82 L/min, respectively (p < 0.0001; both groups) and the difference between the two groups was not significant. Both the treatment groups showed a statistically significant improvement in secondary endpoints at all-time points compared with baseline. The usability questionnaire assessment results showed that the BAI device was preferred by 75% of patients as compared with 25% preferring pMDI. SFC in both BAI and pMDI devices was found to be safe and well tolerated. Conclusion: This is the first study to demonstrate that SFC given through the BAI produces comparable efficacy and safety endpoints as pMDI. Additionally, BAI was the preferred inhaler by patients compared to conventional pMDI.