Identifying the features of an easy-to-use and intuitive dry powder inhaler for asthma and chronic obstructive pulmonary disease therapy: results from a 28-day device handling study,and an airflow resistance study

Background: Many patients with asthma and chronic obstructive pulmonary disease (COPD) symptoms remain insufficiently controlled despite inhalation treatment, with poor inhaler technique recognized as a significant contributor. Dry powder inhalers (DPIs) need less coordination of actuation and inspiration than pressured metered dose inhalers.

Objectives: To assess whether consideration of ‘ideal inhaler’ features during design and development of a new DPI device (Forspiro® Sandoz AG, Switzerland) led to an easy-to-use and reliable inhaler.

Methods: Two studies are reported here: i) 24 adult Accuhaler® users received either limited written instructions (n = 12) or fully illustrated instructions (n = 12) for the Forspiro device; and ii) peak inspiratory flow rates through the Forspiro device were assessed in 30 adult and 10 pediatric patients with asthma and 10 adult patients with COPD.

Results: All subjects understood the correct sequence of actions for the Forspiro device and rated all aspects of handling the device as ‘very easy’ or ‘fairly easy’ (except one uninstructed subject who rated ‘ease of determining number of doses left’ as ‘fairly difficult’). All patients achieved ≥ 35 l/min, thus demonstrating that the Forspiro device provides low-medium airflow resistance.

Conclusions: Inhaler design providing good drug delivery with maximum ease of use may lead to more reliable therapy and improved control of airway diseases.     

Effects of inhaled aminophylline on airway constriction and inflammation in ovalbumin-sensitized guinea pigs

Abstract

Background: The systemic administration of theophylline is useful for asthma treatment. However its narrow therapeutic range makes it difficult to use. Little is known about its potential in inhalation therapy, particularly repeated inhalation.

Objective: The purpose of this study is to investigate the therapeutic usefulness of inhaled aminophylline in an asthma model.

Methods: The effects of pretreatment with inhaled aminophylline (25?mg/mL for 30?min/dose) on airway response and inflammation after an ovalbumin (OVA) challenge and airway hypersensitivity to acetylcholine (Ach) were evaluated using guinea pigs sensitized with OVA.

Results: Aminophylline relaxed the ACh-induced contraction of tracheal smooth muscle in vitro in a concentration-dependent manner. Pretreatment with single-dose aminophylline inhalation suppressed OVA-induced airway constriction to the same extent as the intraperitoneal pretreatment with high-dose aminophylline (10–20?mg/kg). However, pretreatment with single-dose aminophylline inhalation did not suppress eosinophil infiltration into airways (neither bronchoalveolar lavage [BAL] fluid nor lung tissue) and did not suppress airway hyperreactivity to ACh, 24?h after OVA challenge. Repeated inhalation of aminophylline (twice daily for 7 days) suppressed the infiltration of eosinophils and suppressed airway hypersensitivity to ACh. In addition, high concentrations of aminophylline inhibited production of oxygen radicals by BAL cells.

Conclusion: Single-dose inhalation treatment with aminophylline has transient but relatively strong bronchodilating effects due to delivery of high doses into local airways. Repeated inhalation treatment suppressed airway inflammation and hypersensitivity induced by allergens. Therefore, inhaled aminophylline may be useful for asthma treatment.     

Evaluation of efficacy and safety of budesonide delivered via two dry powder inhalers

ABSTRACT

Background: The dry powder inhaler (DPI) device for budesonide inhalation powder 200?μg (DPI?A^*) was redesigned to improve dosing consistency and provide new features (budesonide inhalation powder 90?μg and 180?μg; DPI?B^?).

Objective: Two multicenter, parallel-group, double-blind, randomized, 12-week studies compared the efficacy and safety of budesonide delivered via each DPI versus placebo, and the systemic exposure of budesonide from each device.

Methods: Asthmatic adults with mild-to-moderate asthma (N?=?621) and patients 6–17 years with mild asthma (N?=?516) received budesonide DPI?B 360?μg or DPI?A 400 μg twice-daily (total daily dose 720?μg or 800?μg), budesonide DPI?B 180?μg or DPI?A 200?μg once daily (total daily dose 180?μg or 200?μg), or matching placebo. Change in forced expiratory volume in 1 second (FEV₁) and secondary variables (asthma symptoms, β₂-adrenergic agonist use, peak expiratory flow [PEF], and withdrawals due to worsening asthma) versus placebo were measured.

Results: In both studies, FEV₁ significantly (?p < 0.05) improved for all active treatments versus placebo except once-daily budesonide DPI?B 180?μg in adults. In the adult study, significantly (?p?<?0.05) greater improvements in all secondary variables occurred with all active treatments versus placebo. In the pediatric/adolescent study, improvements in AM/PM PEF were significantly (p?≤?0.011) greater with twice-daily budesonide DPI?B 360?μg versus placebo. Numerically fewer patients in all active-treatment groups withdrew due to worsening asthma versus placebo.

Adverse event profiles were similar among groups. In the pediatric/adolescent study, no significant differences in mean 24-h urine cortisol or cortisol?:?creatinine ratio assessments were observed between the active treatment groups and the placebo group. Although pharmacokinetic variables were generally similar across subgroups in the adult (n?=?77) and pediatric/adolescent (n?=?32) studies, pairwise treatment comparisons of twice-daily budesonide DPI?B 360 μg versus DPI?A 400?μg and once-daily budesonide DPI?B 180?μg versus DPI?A 200?μg showed large variability for the area under the drug plasma concentration–time curve over the dosing interval and the maximum detected drug plasma concentration.

Conclusions: The efficacy and safety of budesonide DPI?A and DPI?B versus placebo were demonstrated across the low to medium inhaled corticosteroid dose range in children?≥?6 years with very mild asthma and adolescents and adults with mild-to-moderate asthma. The study is limited by the evaluation of only two doses for each product in both studies. Additionally, the studies were not designed to test equivalence or noninferiority between the active products. Pharmacokinetic characterization was limited because of the small sample sizes.     

Dry powder inhalers in COPD,lung inflammation and pulmonary infections

Introduction: The number of pulmonary diseases that are effectively treated by aerosolized medicine continues to grow.

Areas covered: These diseases include chronic obstructive pulmonary disease (COPD), lung inflammatory diseases (e.g., asthma) and pulmonary infections. Dry powder inhalers (DPIs) exhibit many unique advantages that have contributed to the incredible growth in the number of DPI pharmaceutical products. To improve the performance, there are a relatively large number of DPI devices available for different inhalable powder formulations. The relationship between formulation and inhaler device features on performance of the drug–device combination product is critical. Aerosol medicine products are drug–device combination products. Device design and compatibility with the formulation are key drug–device combination product aspects in delivering drugs to the lungs as inhaled powders. In addition to discussing pulmonary diseases, this review discusses DPI devices, respirable powder formulation and their interactions in the context of currently marketed DPI products used in the treatment of COPD, asthma and pulmonary infections.

Expert opinion: There is a growing line of product options available for patients in choosing inhalers for treatment of respiratory diseases. Looking ahead, combining nanotechnology with optimized DPI formulation and enhancing device design presents a promising future for DPI development.     

Industry guidance for the selection of a delivery system for the development of novel respiratory products

Introduction: Respiratory diseases remain a target for improved forms of inhalation therapy. However, there are neither regulatory preferences for one type of device over another, nor well-recognized guidelines. This guidance describes factors that should be considered to optimize the choice of delivery system.

Areas covered: This article summarizes the different types of delivery systems with key technical and commercial considerations for selection. It highlights current market trends and opportunities for the future, based on the author’s experience of more than 20 years in this field.

Expert opinion: For a generic drug, low device cost favors a capsule dry powder inhaler (DPI) or a propellant-based metered-dose inhaler (pMDI). Novel particle engineering approaches may allow close matching to the innovator product performance. For novel drugs, most companies favor a bespoke DPI, adding patent protection and aiding brand recognition, despite being expensive to develop. Device features may add differentiation, but “no outcome, no income.” Patient technique and adherence remain problematic, compounded by age, although accessories, including monitors, can help. There are few modern medicines available in nebulized form, so there is value in fast-tracking the nebulized formulations from Phase I studies through to market in parallel to the chosen inhaler.     

Anticonvulsant hypersensitivity syndrome: an update

Introduction: Long-acting β-agonists (LABAs) added to inhaled corticosteroids (ICS) reduce symptoms, improve lung function and enhance overall asthma control. However, several studies have indicated an increased risk of asthma mortality and asthma-related serious adverse events and the FDA recently mandated restrictions to the use of LABAs in asthma.

Areas covered: This review highlights the clinical studies on which safety analyses pertaining to salmeterol and formoterol have been based and then focuses on recent meta-analyses of safety outcomes with and without consideration of concomitant ICS.

Expert opinion: The phenomenon of masking of inflammation by LABA if ICS dose is insufficient underscores the potential for confounding in determining real safety risks. Under-treatment with ICS and differential dosing of ICS in many trials are major factors driving the LABA safety concern. The FDA meta-analysis, when stratified for mandatory ICS use, found no significant increase in the composite outcome of asthma mortality, intubations and hospitalizations. Add-on therapy with LABA is effective and safe if the dose of ICS is adequate to treat airway inflammation. LABA and ICS given in a single device will negate the possibility of LABA monotherapy which is contraindicated. The FDA has recommended that LABAs be withdrawn when control is achieved with combination therapy but recent evidence suggests this may result in loss of symptom control.     

Models of deposition,pharmacokinetics, and intersubject variability in respiratory drug delivery

ABSTRACT

Introduction: Aerosol drug delivery to the lungs via inhalation is widely used in the treatment of respiratory diseases. The deposition pattern of inhaled particles within the airways of the respiratory tract is key in determining the initial delivered dose. Thereafter, dose-dependent processes including drug release or dissolution, clearance, and absorption influence local and systemic exposure to inhaled drugs over time.

Areas covered: Empirical correlations, numerical simulation, and in vitro airway geometries that permit improved prediction of extrathoracic and lung deposition fractions in a variety of age groups and breathing conditions are described. Efforts to link deposition models with pharmacokinetic models predicting lung and systemic exposure to inhaled drugs over time are then reviewed. Finally, new methods to predict intersubject variability in extrathoracic deposition, capturing variability in both size and shape of the upper airways, are highlighted.

Expert opinion: Recent work has been done to expand in vitro deposition experiments to a wide range of age groups and breathing conditions, to link regional lung deposition models with pharmacokinetic models, and to improve prediction of intersubject variability. These efforts are improving predictive understanding of respiratory drug delivery, and will aid the development of new inhaled drugs and delivery devices.     

Usage of inhalation devices in asthma and chronic obstructive pulmonary disease: a Delphi consensus statement

Objectives: The study aimed to assess usage of inhalation devices in asthma and chronic obstructive pulmonary disease (COPD).

Methods: In this two-round Delphi survey, 50 experts in asthma and COPD completed a 13-item, Internet-based, self-administered questionnaire about choice of inhalation device, training and monitoring of inhalation techniques, the interchangeability and the role of costs in the selection of inhalation devices. For each item, the median (central tendency) and interquartile ranges (degree of consensus) were calculated.

Results: Experts considered that the choice of inhalation device was as important as that of active substance (very good consensus) and should be driven by ease of use (good to very good consensus) and teaching (very good consensus). Experts recommended giving oral and visual instructions (good consensus) and systematic monitoring inhalation techniques. Pulmonologists and paramedics have predominantly educational roles (very good consensus). Experts discouraged inhalation device interchangeability (good consensus) and switching for cost reasons (good to very good consensus) without medical consultation (good consensus).

Conclusions: The results of this survey thus suggested that inhalation devices are as important as active substances and training and monitoring are essential in ensuring effective treatment of asthma and COPD. Inhalation device switching without medical consultation should be avoided.     

Optimizing the Entrainment Geometry of a Dry Powder Inhaler: Methodology and Preliminary Results

Purpose

For passive dry powder inhalers (DPIs) entrainment and emission of the aerosolized drug dose depends strongly on device geometry and the patient’s inhalation manoeuvre. We propose a computational method for optimizing the entrainment part of a DPI. The approach assumes that the pulmonary delivery location of aerosol can be determined by the timing of dose emission into the tidal airstream.

Methods

An optimization algorithm was used to iteratively perform computational fluid dynamic (CFD) simulations of the drug emission of a DPI. The algorithm seeks to improve performance by changing the device geometry. Objectives were to achieve drug emission that was: A) independent of inhalation manoeuvre; B) similar to a target profile. The simulations used complete inhalation flow-rate profiles generated dependent on the device resistance. The CFD solver was OpenFOAM with drug/air flow simulated by the Eulerian-Eulerian method.

Results

To demonstrate the method, a 2D geometry was optimized for inhalation independence (comparing two breath profiles) and an early-bolus delivery. Entrainment was both shear-driven and gas-assisted. Optimization for a delay in the bolus delivery was not possible with the chosen geometry.

Conclusions

Computational optimization of a DPI geometry for most similar drug delivery has been accomplished for an example entrainment geometry.

     

Challenges and advances in the development of inhalable drug formulations for cystic fibrosis lung disease

Introduction: Cystic fibrosis (CF) is a multisystem genetic disorder, which usually results in significant respiratory dysfunction. At present there is no cure for CF, but advances in pharmacotherapy have gradually increased the life expectancy of CF patients. As many drugs used in the therapy of CF are delivered by inhalation, the demand for effective and convenient inhalational CF drug formulations will grow as CF patients live longer. Knowledge of the current limitations in inhalational CF drug delivery is critical in identifying new opportunities and designing rational delivery strategies.

Areas covered: This review discusses current and emerging therapeutic agents for CF therapy, selected physiological challenges to effective inhalational medication delivery, and various approaches to overcoming these challenges. The reader will find an integrated view of the known inhalational drug delivery challenges and the rationales for recent investigational inhalational drug formulations.

Expert opinion: An ideal drug/gene delivery system to CF airways should overcome the tenacious sputum, which presents physical, chemical and biological barriers to effective transport of therapeutic agents to the targets and various cellular challenges.     

Selective serotonin reuptake inhibitors: a review of efficacy and tolerability in depression

Background: In asthma small airways inflammation often persists despite inhaled corticosteroids therapy. Objective: To discuss the effects of ciclesonide, a newer inhaled corticosteroid on small airways inflammation and the reliability of some biomarkers of small airways inflammation in asthma. Methods and results: Evaluation of a study assessing the short-term effects of ciclesonide on small airways inflammation in patients with mild to moderate asthma. Conclusions: Ciclesonide could have beneficial effects on small airways inflammation and some of the outcome measures used as efficacy endpoints could represent possible biomarkers of small airways involvement in obstructive chronic respiratory diseases.     

Improving inhaler technique,adherence to therapy and the precision of dosing: major challenges for pulmonary drug delivery

Introduction: The inhaled route has many advantages, but requires the patient to use, and to master the use of, an inhaler device. Poor inhaler technique and non-adherence to therapy lead to a highly variable lung dose in clinical practice, with subsequent loss of clinical efficacy and wastage of economic resources.

Areas covered: This paper discusses problems of poor inhaler technique, non-adherence to inhaler therapy, other issues relating to the precision of dose delivery, the consequences of these problems and how they can be addressed.

Expert opinion: The precision of dosing by the pulmonary route can be improved by appropriate choice of inhaler device and by education. It is vital to educate patients about their disease, about the importance of taking prescribed medications and about correct inhaler use. One-on-one sessions with healthcare professionals probably represent the most effective educational method. For some drugs and patient groups, inhalers containing small microprocessors may also be used to control inhalation technique, and hence, to obtain a more reproducible lung dose. As the range of drugs delivered by inhalation increases, the need for correct inhaler technique, adherence to therapy and precise dosing becomes more and more important.     

Relative systemic availability of budesonide in patients with asthma after inhalation from two dry powder inhalers

ABSTRACT

Background: To improve dosing consistency and product features, budesonide inhalation powder delivered via a dry powder inhaler (DPI) (DPI?A^* 200?μg) was redesigned to include lactose, a newly shaped mouthpiece, and a new dose indicator (DPI?B^*). Budesonide DPI?B is available in two strengths (90?μg, 180?μg).

Objective: To compare the relative rate and extent of the systemic availability of budesonide inhaled via DPI?A and DPI?B and test for systemic absorption bio­equivalence.

Methods: Adults (n?=37) with asthma as defined by the American Thoracic Society were randomized in an open-label, crossover, single-center, single-dose study to budesonide DPI?A 200?μg × 4 inhalations, budesonide DPI?B 180?μg × 4 inhalations, or budesonide DPI?B 90?μg × 8 inhalations, on 3 days, each separated by a washout period of?≥?5 days. Plasma samples were collected immediately before and up to 12?h after dosing. Primary pharmacokinetic variables were area under the drug plasma concentration–time curve from 0 to infinity (AUC_0–∞) and maximum plasma concentration (C_max); plasma concentration at 12?h (C_12h) and time to maximum plasma concentration (T_max) were secondary variables. Treatments were considered bioequivalent if the 90% confidence intervals (CIs) for their AUC_0–∞ and C_max ratios fell between 80 and 125%. Adverse events were collected.

Results: The 90% CIs for the ratios of AUC_0–∞ and C_max for budesonide DPI?A 200?μg and DPI?B 180?μg and for both budesonide DPI?B strengths fell between 80% and 125% (AUC_0–∞: budesonide DPI?B 180?μg × 4/DPI?A 200?μg × 4: 96.3% [90 % CI: 90.9, 102.1]; budesonide DPI?B 180?μg × 4/DPI?B 90?μg × 8: 92.2% [90 % CI: 87.0, 97.7]; C_max: (budesonide DPI?B 180?μg × 4/DPI?A 200?μg × 4: 100.4% [95 % CI: 92.1, 109.4]; budesonide DPI?B 180?μg × 4/DPI?B 90?μg × 8: 94.4% [90 % CI: 86.6, 102.9]). No differences in C_12h and T_max were found between treatments. All treatments were well tolerated.

Conclusions: Budesonide DPI?A 200?μg and DPI?B 180?μg have systemic absorption bioequivalence, and DPI?B 90?μg and 180?μg are dose-strength equivalent when administered at the same dose. These results may not be generalized to all patients with asthma, as this analysis included only patients with mild-to-moderate asthma aged?≥?19 years.     

Dry powder inhalation: past,present and future

Introduction: Early dry powder inhalers (DPIs) were designed for low drug doses in asthma and COPD therapy. Nearly all concepts contained carrier-based formulations and lacked efficient dispersion principles. Therefore, particle engineering and powder processing are increasingly applied to achieve acceptable lung deposition with these poorly designed inhalers.

Areas covered: The consequences of the choices made for early DPI development with respect of efficacy, production costs and safety and the tremendous amount of energy put into understanding and controlling the dispersion performance of adhesive mixtures are discussed. Also newly developed particle manufacturing and powder formulation processes are presented as well as the challenges, objectives, and new tools available for future DPI design.

Expert opinion: Improved inhaler design is desired to make DPIs for future applications cost-effective and safe. With an increasing interest in high dose drug delivery, vaccination and systemic delivery via the lungs, innovative formulation technologies alone may not be sufficient. Safety is served by increasing patient adherence to the therapy, minimizing the use of unnecessary excipients and designing simple and self-intuitive inhalers, which give good feedback to the patient about the inhalation maneuver. For some applications, like vaccination and delivery of hygroscopic formulations, disposable inhalers may be preferred.     

Inhalation exposure of nano-scaled titanium dioxide (TiO2) particles alters the inflammatory responses in asthmatic mice

Abstract

Context: Titanium dioxide (TiO₂) nanoparticles (NPs) are regarded as relatively non-toxic in concentrations occurring in occupational environments. Nevertheless, it is conceivable that adverse health effects may develop in sensitive populations such as individuals with respiratory diseases.

Objective: We investigated whether single or repeated exposure to TiO₂ could aggravate inflammatory responses in naïve mice and mice with ovalbumin (OVA)-induced airway inflammation.

Methods: Exposure to aerosolized TiO₂ was performed during OVA sensitization, before, or during the OVA challenge period. The effects on respiratory physiology, inflammatory cells in bronchoalveolar lavage (BAL) and inflammatory mediators in BAL and serum were assessed 24?h after the last OVA challenge or TiO₂ exposure.

Results: A single exposure of TiO₂ had a marked effect on responses in peripheral airways and increasing infiltration of neutrophils in airways of naïve animals. Marked aggravation of airway responses was also observed in animals with allergic disease provided that the single dose TiO₂ was given before allergen challenge. Repeated exposures to TiO₂ during sensitization diminished the OVA-induced airway eosinophilia and airway hyperresponsiveness but concomitant exposure to TiO₂ during the OVA challenge period resulted in neutrophilic airway inflammation and a decline in general health condition as indicated by the loss of body weight.

Conclusion: We conclude that inhalation of TiO₂ may aggravate respiratory diseases and that the adverse health effects are highly dependent on dose and timing of exposure. Our data imply that inhalation of NPs may increase the risk for individuals with allergic airway disease to develop symptoms of severe asthma.     

Surface-modified Antiasthmatic Dry Powder Aerosols Inhaled Intratracheally Reduce the Pharmacologically Effective Dose

Purpose. The aim of this study was to construct a reliable dry powder inhalation (DPI) testing system for use in guinea pigs. Using this system, we were able to demonstrate the superiority of pulmonary administration of hydrophilically surface-modified pranlukast hydrate powder (SM-DP) over IV and PO administration as reflected in improved pharmacological action. Our ultimate aim is the development of an ideal treatment system for bronchial asthma involving topical administration to the lung. Methods. The reliability of the present DPI system was validated by continuously monitoring the concentration and particle size distribution of aerosols generated with an ambient particulate monitor and an Andersen air sampler, respectively. The pharmacological effect of SM-DP intratracheally administered to guinea pig was investigated by measuring the degree of bronchoconstriction and microvascular leakage induced by leukotriene D₄. Results. The mass concentration of aerosols generated by the DPI system was stable and the mass median aerodynamic diameter of aerosols insufflated from the respirator of the DPI system ranged from 1.4 to 1.7 m, within respirable limits. Inhibition of bronchoconstriction and airway microvascular leakage induced by leukotriene D₄ was achieved successfully with a dramatically lower dose of DP, or a further lower dose of SM-DP, comparable with that of the drug solution injected intravenously. The plasma pranlukast hydrate level with SM-DP at 50% inhibition of bronchoconstriction and airway microvascular leakage was reduced to 1/10 or less that following IV and PO administration. Conclusions. The hydrophilically surface-modified pranlukast hydrate powders were ideally aerosolized by the present DPI system, and were uniformly deposited in the lung lobes after inhalation. The pulmonary administration system with SM-DP is strongly recommended as an ideal system for the treatment of bronchial asthma in order to avoid systemic side-effects due to a dramatically reduced ED₅₀, comparable with or lower than IV, and the low plasma concentration of drug, 1/12 or less than that following IV and PO administration.     

Large Porous Particles for Sustained Protection from Carbachol-Induced Bronchoconstriction in Guinea Pigs

Purpose. To determine whether a new formulated albuterol aerosol could sustain inhibition to bronchoconstriction for approximately one day in guinea pigs challenged with carbachol. Methods. Large and porous particles, comprising a combination of endogenous or PDA-approved excipients and albuterol sulfate, were prepared by spray drying using a NIRO portable spray drier. The anesthetized animals inhaled 5 mg of large porous or small nonporous particles by forced ventilation via cannulae inserted in the lumen of their exposed tracheae. At regular intervals over a period of 36 hours after drug delivery, airway resistance was determined in response to carbachol challenge dose. Results. Whereas inhalation of small nonporous albuterol particles protected from the carbachol-induced bronchoconstriction for up to 5 hours, inhalation of large porous albuterol particles produced a significant inhibition of carbachol-induced bronchoconstriction for at least 16 hours. Conclusions. The absence of substantial side effects, verified over a period of 24 hours by evaluating cardio-respiratory parameters as well as pulmonary inflammation, supports the utility of large porous albuterol particles for sustained therapies in asthma and other types of lung disease.Dr. Ben-Jebria is also affiliated with     

Thymic stromal lymphopoietin: a central regulator of allergic asthma

Introduction: Epithelial cell-derived mediators have emerged as key players for instigating local remodeling and the associated cellular inflammation in asthmatic airways. In particular, the epithelial-derived cytokine, thymic stromal lymphopoietin (TSLP), has been identified as a master switch for allergic inflammation.

Areas covered: TSLP is expressed by structural and immune cells at the site of allergen entry in the airways. Stimuli for release of TSLP include common triggers of asthma symptoms, and TSLP levels correlate with disease severity. TSLP regulates helper T cell 2 (Th2) humoral immunity through upregulating OX40L on dendritic cells (DCs), which drives Th2 lymphocytes; however, activation of several other cells by TSLP also supports the development of Th2 inflammation. Animal models of asthma demonstrate that increased levels of TSLP can induce many of the characteristics of asthma.

Expert opinion: The work conducted to date supports a critical role of TSLP in the pathogenesis of allergic asthma. The first clinical trial to block the downstream effects of OX40L has shown reduced levels of circulating IgE and airway eosinophils, confirming the importance of TSLP-induced OX40L levels on DCs. Clinical trials with TSLP blockade are underway and will unequivocally confirm whether TSLP is indeed a key driver of allergic inflammation in asthma.     

Comparing the efficacy and safety of salmeterol/fluticasone pMDI versus its mono-components,other LABA/ICS pMDIs and salmeterol/fluticasone Diskus in patients with asthma

Introduction: Pressurized metered dose inhalers (pMDIs) are evolving to be a very effective drug delivery option in patients with airway diseases. They offer comparable lung deposition and reduced oropharyngeal deposition similar with the dry powder inhalers. As recommended by the Global Initiative for Asthma guidelines, the ideal maintenance treatment for asthma is a combination of long acting β₂-agonists (LABAs) and inhaled corticosteroids (ICSs). One of the available LABA/ICS combinations is the salmeterol/fluticasone propionate combination (SFC) and a plethora of evidence supports its clinical efficacy and safety.

Areas covered: This article focuses on the SFC hydrofluroalkane pMDI and compares the efficacy and tolerability with salmeterol and fluticasone given individually, and with other fixed-dose combinations namely formoterol/fluticasone, formoterol/beclometasone and formoterol/mometasone furoate, all delivered via pMDI. Also discussed is the efficacy and tolerability of the SFC delivered via a pMDI, as compared to the SFC via Diskus.

Expert opinion: pMDIs play an important role in inhalation therapy given the low price, low maintenance and convenience of use. LABA/ICS combinations are the preferred choice of medication for asthma treatment and will remain the mainstay for the decades to come. In our opinion, pMDI should be the choice of device to administer LABA/ICS maintenance therapy, as it is already being used by the patients for reliever therapy, which may eventually improve patient adherence and compliance.     

Micro- and nanocarrier-mediated lung targeting

Importance of the field: Drug delivery to lungs appears to be an attractive proposition on account of the large surface area of the alveolar region; it provides tremendous opportunities to improve drug therapies both systemically and locally using new drug delivery systems. Administration of drugs directly to the lungs is the most appropriate route in the treatment of asthma and other pulmonary diseases such as tuberculosis, chronic obstructive pulmonary disease and lung cancer.

Areas covered in this review: This review focuses on the utilization of nano- and microcarriers such as microspheres, nanoparticles, liposomes, niosomes and dendrimers for targeted delivery of bioactive molecules to lungs.

What the reader will gain: This review sheds light on the current status of nano- and microcarrier-mediated lung targeting of bioactive compounds.

Take home message: The literature review shows that carriers could supplement sustained drug delivery to the lungs, extended duration of action, reduced therapeutic dose, improved patient compliance, and reduced adverse effects of highly toxic drugs. There is still a need to identify more specific receptors that are present exclusively in the lungs. The identification of such receptors may also facilitate drug targeting to further specific parts of the lungs, such as bronchioles and alveoli.