Respiratory Drugs Research Articles

Instant velocity and consistency of emitted cloud change by the different levels of canister filling with Metered Dose Inhalers (MDIs), but not with Soft Mist Inhalers (SMIs): a\xa0bench study

BackgroundInhalation is the preferred route for respiratory drug delivery, but several factors contribute to the variability of the respirable dose fraction. Instant velocity and the dynamic characteristics of the droplet cloud represent crucial factors. Aim was to measure and compare the instant velocity and the consistency of emitted cloud from five different MDIs (A - Salbutamol sulphate 100mcg, GSK; B - Salbutamol sulphate 100mcg, Valeas; C - Salmeterol xinafoate/Fluticasone propionate 25/125mcg, GSK; D - Formoterol fumarate/Bechlomethasone propionate 6/100mcg, Chiesi; E - Formoterol fumarate/Fluticasone dipropionate 5/125mcg, Mundipharma) and one SMI (Tiotropium bromide 5mcg, Boehringer Ingelheim), at different distance from the nozzle and canister filling.MethodsMeasurements were made at 90, 50, and 10% of canister filling, and at 5, 10, and 20 cm from the nozzle, for a total of 972 puffs. A high speed video photography protocol was adopted and high speed cameras (1.200 frames/sec.) were used. Data were acquired by means of specialized softwares. Temperature, humidity, and vibrations occurrence were strictly controlled during measurements. Statistics: Anova and p < 0.05 were accepted as the minimum significance level.ResultsMDIs generated different Instant velocities: MDI B generated the highest, while MDI A the lowest. As expected, velocity decreased in proportion to the distance from the nozzle. Except with MDI C, instant velocity decreased significantly over the first 50% of canister emptying, but dropped by >33% at 90% of emptying with all other MDIs (p < 0–037; p < 0.001; p < 0.005, and p < 0.001, respectively). Instant velocity was extremely lower (p < 0.001) and constant for all levels of canister filling (p = ns) with SMI. All MDIs had a very fast jet phase, ranging 0.01–0.03 s at 10 cm, and 0.03–0.05 s at 20 cm from the nozzle, without any significant difference from each other (p = ns). MDIs generated a cloud similarly tight (p = ns) at 10 and 20 cm from the nozzle, while it was extremely wider and constant with the SMI (p = 0–001). Also the cloud turbulence was minimized during the SMI emission.Discussion and ConclusionsMDIs are characterized by a substantial variability in both their instant velocity and consistency of the emitted cloud at different levels of canister filling. SMI generates a much slower soft mist cloud which is constantly homogeneous and independent of canister emptying. These peculiarities assessed at bench are suggesting a higher dose consistency and a much more effective therapeutic performance also in real life.

Large porous particles for respiratory drug delivery. Glycine-based formulations

Large porous particles are becoming increasingly popular as carriers for pulmonary drug delivery with both local and systemic applications. These particles have high geometric diameters (5–30μm) but low bulk density (~0.1g/cm3 or less) such that the aerodynamic diameter remains low (1–5μm). In this study salbutamol and budesonide serve as model inhalable drugs with poor water solubility. A novel method is proposed for the production of dry powder inhaler formulations with enhanced aerosol performance (e.g. for salbutamol-glycine formulation the fine particle fraction (FPF≤4.7μm) value is 67.0±1.3%) from substances that are poorly soluble in water. To overcome the problems related to extremely poor aqueous solubility of the APIs, not individual solvents are used for spray freeze-drying of API solutions, but organic-water mixtures, which can form clathrate hydrates at low temperatures and release APIs or their complexes as fine powders, which form large porous particles after the clathrates are removed by sublimation. Zwitterionic glycine has been used as an additive to API directly in solutions prior to spray freeze-drying, in order to prevent aggregation of powders, to enhance their dispersibility and improve air-flow properties. The clathrate-forming spray freeze-drying process in the multi-component system was optimized using low-temperature powder X-ray diffraction and thermal analysis.

Chronic Disease Prevalence Among Mothers Delivering in the United States, 2004-2013 [38N

INTRODUCTION: Reasons for nationwide increases in delivery-associated maternal morbidity and mortality are poorly understood. Pre-existing chronic disease increases the risk of obstetric complications, and there is a need to understand trends in chronic disease burden among the childbearing population. METHODS: We conducted a serial cross-sectional analysis of the National Inpatient Sample between 2004 and 2013. We used multivariable logistic regression, adjusted for age, income, and insurance status, to examine trends in chronic disease among delivery hospitalizations. Chronic disease was measured with ICD-9CM codes for 8 common conditions known to impact obstetric outcomes. RESULTS: Our sample was comprised of 8,307,761 delivery hospitalizations between 2004-2013. The mean age of delivering mothers was 27.7. The most prevalent conditions were respiratory disease, hypertension, and drug abuse (3.0, 1.9 and 1.4 per 100 delivery hospitalizations, respectively). In adjusted analyses, records in 2012/2013 were more likely than those in 2004/2005 to include diagnoses of diabetes, hypertension, respiratory disease, liver disease, kidney disease, and drug use (all P less than 0.001) and less likely to have diagnoses of heart disease (P less than 0.001) or HIV (P equal to 0.02). Delivery hospitalizations in 2012/2013 were also more likely than those in 2004/2005 to be complicated by at least one or at least two chronic conditions (both P less than 0.001). CONCLUSION: Chronic disease burden increased significantly among delivering mothers between 2004/2005 and 2012/2013. Higher proportions of women with chronic conditions and higher numbers of chronic conditions per patient may contribute to increases in delivery-associated morbidity and mortality.

An In Vitro Aerosolization Efficiency Comparison of Generic and Branded Salbutamol Metered Dose Inhalers

Background: Due to the high rate of pulmonary diseases, respiratory drug delivery systems have been attracted excessive attention for the past decades. Because of limitations and growing drug bill, physicians are encouraged to prescribe generically whenever possible. The purpose of this study was to evaluate whether there was any significant difference in aerosolization performance between a reference brand Salbutamol (A) Metered Dose Inhalers (MDIs) and two generic products (B and C). Methods: The aerosolization performance of MDIs was evaluated by calculating aerosolization indexes including fine particle fraction (FPF), fine particle dose (FPD), geometric standard deviation (GSD) and mass median aerodynamic diameters (MMAD) by using the next generation impactor. Results: Although aerosolization indexes of MDI A were superior than the Iranian brands, but the differences were not statistically significant. Conclusion: These results verified that generic MDIs deliver similar quantities of Salbutamol to the reference brand and aerosolization performance parameters of generic Salbutamol MDIs did not differ significantly from the reference brand.

In Vitro and in Silico Tools To Assess Extent of Cellular Uptake and Lysosomal Sequestration of Respiratory Drugs in Human Alveolar Macrophages

Accumulation of respiratory drugs in human alveolar macrophages (AMs) has not been extensively studied in vitro and in silico despite its potential impact on therapeutic efficacy and/or occurrence of phospholipidosis. The current study aims to characterize the accumulation and subcellular distribution of drugs with respiratory indication in human AMs and to develop an in silico mechanistic AM model to predict lysosomal accumulation of investigated drugs. The data set included 9 drugs previously investigated in rat AM cell line NR8383. Cell-to-unbound medium concentration ratio (Kp,cell) of all drugs (5 μM) was determined to assess the magnitude of intracellular accumulation. The extent of lysosomal sequestration in freshly isolated human AMs from multiple donors (n = 5) was investigated for clarithromycin and imipramine (positive control) using an indirect in vitro method (±20 mM ammonium chloride, NH4Cl). The AM cell parameters and drug physicochemical data were collated to develop an in silico mechanistic AM model. Three in silico models differing in their description of drug membrane partitioning were evaluated; model (1) relied on octanol-water partitioning of drugs, model (2) used in vitro data to account for this process, and model (3) predicted membrane partitioning by incorporating AM phospholipid fractions. In vitro Kp,cell ranged >200-fold for respiratory drugs, with the highest accumulation seen for clarithromycin. A good agreement in Kp,cell was observed between human AMs and NR8383 (2.45-fold bias), highlighting NR8383 as a potentially useful in vitro surrogate tool to characterize drug accumulation in AMs. The mean Kp,cell of clarithromycin (81, CV = 51%) and imipramine (963, CV = 54%) were reduced in the presence of NH4Cl by up to 67% and 81%, respectively, suggesting substantial contribution of lysosomal sequestration and intracellular binding in the accumulation of these drugs in human AMs. The in vitro data showed variability in drug accumulation between individual human AM donors due to possible differences in lysosomal abundance, volume, and phospholipid content, which may have important clinical implications. Consideration of drug-acidic phospholipid interactions significantly improved the performance of the in silico models; use of in vitro Kp,cell obtained in the presence of NH4Cl as a surrogate for membrane partitioning (model (2)) captured the variability in clarithromycin and imipramine Kp,cell observed in vitro and showed the best ability to predict correctly positive and negative lysosomotropic properties. The developed mechanistic AM model represents a useful in silico tool to predict lysosomal and cellular drug concentrations based on drug physicochemical data and system specific properties, with potential application to other cell types.

Self-medication practice in Ethiopia: a systematic review.

BackgroundSelf-medication patterns vary among different populations, and are influenced by many factors. No review has been done that comprehensively expresses self-medication practice in Ethiopia. The aim of this study was to provide an overview of the literature on self-medication practice in Ethiopia.Materials and methodsDatabases (PubMed, Google Scholar, ResearchGate, and Hinari) were searched for published studies on the practice of self-medication in Ethiopia without restriction in the year of publication or methodology. Some studies were also identified through manual Google search. Primary search terms were “self medication”, “Ethiopia”, “self care”, “non-prescription”, “OTC drug use”, “drug utilization”, and “drug hoarding”. Studies that measured knowledge only or attitude only or beliefs only and did not determine the practice of self-medication were excluded.ResultsThe database search produced a total of 450 papers. After adjustment for duplicates and inclusion and exclusion criteria, 21 articles were found suitable for the review. All studies were cross-sectional in nature. The prevalence of self-medication varied from 12.8% to 77.1%, with an average of 36.8%. Fever/headache, gastrointestinal tract diseases, and respiratory diseases were the commonest illnesses/symptoms for which self-medication was taken. The major reasons for practicing self-medication were previous experience of treating a similar illness and feeling that the illness was mild. Analgesics/antipyretics, antimicrobials, gastrointestinal drugs, and respiratory drugs were the common drug classes used in self-medication. Mainly, these drugs were obtained from drug-retail outlets. The use of self-medication was commonly suggested by pharmacy professionals and friends/relatives.ConclusionSelf-medication practice is prevalent in Ethiopia and varies in different populations and regions of the country. Some of the self-medication practices are harmful and need prompt action. Special attention should be given to educating the public and health care providers on the types of illnesses that can be self-diagnosed and self-treated and the types of drugs to be used for self-medication.

Clinical Characterization of a Large Population of Subjects with Respiratory Vs Cutaneous Non-Steroidal Anti-Inflammatory Drugs (NSAID) Hypersensitivity Reactions

Clinical Characterization of a Large Population of Subjects with Respiratory Vs Cutaneous Non-Steroidal Anti-Inflammatory Drugs (NSAID) Hypersensitivity Reactions

Innovations in Outcomes and Designs of Clinical Trials for Respiratory Drug Development

Clinical trials for the development of respiratory drugs have for years been reliant upon measurements of physiologic tests, combined with the use of questionnaires. New drugs were mostly administered by inhalation and increasingly in fixed combinations. However, these lung function tests have a lack of sensitivity for patient-relevant clinical outcomes. Moreover, new insights in phenotypes and endotypes of these diseases in the basic mechanisms and the discovery of new targets for therapy, have led to the need for a more personalized patient-centered approach and precision medicine. In recent years, a great number of techniques have been proposed but some need further validation. These include fractional exhaled nitric oxide, health-related quality of life and the use of biomarkers like blood and sputum eosinophils and neutrophils, IgE, sIgE, periostin, copeptin and specific cytokines. Additionally, exhaled breath condensate and lung deposition studies by functional residual imaging and by local bronchial pharmacokinetics can be used. In rare diseases like cystic fibrosis, Lung Clearance Index and CT and PET scan fusion images seem to be valuable outcome measurements. Lastly leverage of lung function tests can be done by using body plethysmography, measuring respiratory impedance, variability and the use of modeling and simulation. The need for a patient-centric approach through all stages of clinical development is becoming mandatory. So, an evolution from classical randomized clinical trials (RCTs) to more efficient and patient-relevant designs will be seen more in the future. RCTs will remain necessary for regulatory submission but more efficient and adaptive designs with lower heterogeneity and the use of pragmatic trials are needed. This evolution from undefined targets to a more targeted approach will lead us closer to precision medicine. In this overview, the unmet medical need for better outcomes and study designs in the development of treatments for respiratory diseases, are discussed.

The Global Usability Score: A Novel Comprehensive Tool for Assessing, Ranking, and Compare Usability of Inhalers in Patients Requiring Airway Treatments

Introduction: The inhalation route is the best choice for respiratory drug delivery, but benefits to patients are strictly related to the proper use of inhalers. The role of patients’ view point (such as: their intuitivity, preference, acceptance, and satisfaction) were extensively investigated, even if other factors, unrelated to their personal beliefs, can further affect inhaler usability. Aim: to define a specific tool for easily assessing, ranking, and comparing the real usability of whatever inhaler by a single, comprehensive score, also based on objective measurements. Methods: A specific, anonymous questionnaire was validated. The Questionnaire consists of four main sections (Introductory; Assessing Track; Global Score calculation, Patient’s personal data). Questions are twenty-seven, all scored: twenty-two addressed to the patient, and five to the expert nurse, who has to conduct the independent assessments. The sum of the eight sub-scores of the Assessing Track will represent the final Global Usability Score- GUS, which ranges 0-50 points for each inhaler; higher the GUS value, higher the real usability will be. Results: the comprehension of all questions at their first reading was >97% in the final version of the GUS Questionnaire, for both patients and nurses participating to the questionnaire development. Discussion: usability of inhalers is a complex and multifaceted issue. When assessing usability, it should be taken into account that the role of patients’ beliefs differently integrates the role of other objective determinants which are unrelated to the sole patients’ viewpoint. Terms like intuitivity, preference, acceptability, or satisfaction should not be used as synonyms for usability, because too related to the patients’ subjectivity only. Conclusions: the Global Usability Score represents the first comprehensive score for assessing, ranking, and comparing objectively the contribution of all main components of inhaler usability, and then provide an effective and motivated standard of choice.

Transport and deposition of cohesive pharmaceutical powders in human airway

Pharmaceutical powders used in inhalation therapy are in the size range of 1-5 microns and are usually cohesive. Understanding the cohesive behaviour of pharmaceutical powders during their transportation in human airway is significant in optimising aerosol drug delivery and targeting. In this study, the transport and deposition of cohesive pharmaceutical powders in a human airway model is simulated by a well-established numerical model which combines computational fluid dynamics (CFD) and discrete element method (DEM). The van der Waals force, as the dominant cohesive force, is simulated and its influence on particle transport and deposition behaviour is discussed. It is observed that even for dilute particle flow, the local particle concentration in the oral to trachea region can be high and particle aggregation happens due to the van der Waals force of attraction. It is concluded that the deposition mechanism for cohesive pharmaceutical powders, on one hand, is dominated by particle inertial impaction, as proven by previous studies; on the other hand, is significantly affected by particle aggregation induced by van der Waals force. To maximum respiratory drug delivery efficiency, efforts should be made to avoid pharmaceutical powder aggregation in human oral-to-trachea airway.

Medication package inserts: how far do they adhere to the guidelines?

Background: Package Insert (PI) is a document that is provided with the package of a drug. It is chiefly directed at the prescribers and is set to provide information for the safe and effective use of the respective drug. This study was conducted to assess the completeness of clinical information provided in the currently available PIs.Methods: PIs were collected from pharmacies located at various parts of Bangalore over three months. A total of 310 drugs were checked for package inserts (PI) and 192 PI’s were collected. They were analysed based on the criteria mentioned in Schedule D of Drug and Cosmetic act 1945.Results: Out of 192 PIs, 33 were repeated and so were not taken into account. Hence, 159 PIs were analysed. Among 159 PIs, 43 (27.04%) were of Cancer chemotherapy drugs; 19 (11.94%) of antibiotics, 18 of anti-diabetic drugs, 13 (8.17%) of Vitamins and minerals, 10 (6.28%) of Cardiac drugs, 9 (5.66%) of Respiratory drugs, 6 (3.77%) of CNS drugs, 5 (3.14%) of Ophthalmic eye solutions, 4 (2.51%) of Hormones and reproductive system, 4 (2.51%) of GIT, 4 (2.51%) of Antifungals, 3 (1.88%) of steroids, and 21 (13.20%) of miscellaneous drugs respectively. Out of them, the PIs that belonged to “A”, “B”, and “C” categories were 5 (3.14%), 150 (94.33%), and 4 (2.51%) respectively. It was observed that the PIs were inadequate in many aspects. Majority of the PIs had unclear instructions about drug usage, special precautions, ability to drive and use machines and adverse effects to name a few.Conclusions: This study showed that many of the drugs now days come without PI. Also of the available ones, very few fulfil all the criteria mentioned in the guidelines. With the growing sales of over the counter drugs in India, it is important for companies to dispense PIs with all the drugs. PIs oriented toward educating the patient are the need of the hour.

Computationally efficient analysis of particle transport and deposition in a human whole-lung-airway model. Part II: Dry powder inhaler application

Pulmonary drug delivery is becoming a favored route for administering drugs to treat both lung and systemic diseases. Examples of lung diseases include asthma, cystic fibrosis and chronic obstructive pulmonary disease (COPD) as well as respiratory distress syndrome (ARDS) and pulmonary fibrosis. Special respiratory drugs are administered to the lungs, using an appropriate inhaler device. Next to the pressurized metered-dose inhaler (pMDI), the dry powder inhaler (DPI) is a frequently used device because of the good drug stability and a minimal need for patient coordination. Specific DPI-designs and operations greatly affect drug-aerosol formation and hence local lung deposition. Simulating the fluid-particle dynamics after use of a DPI allows for the assessment of drug-aerosol deposition and can also assist in improving the device configuration and operation. In Part I of this study a first-generation whole lung-airway model (WLAM) was introduced and discussed to analyze particle transport and deposition in a human respiratory tract model. In the present Part II the drug-aerosols are assumed to be injected into the lung airways from a DPI mouth-piece, forming the mouth-inlet. The total as well as regional particle depositions in the WLAM, as inhaled from a DPI, were successfully compared with experimental data sets reported in the open literature. The validated modeling methodology was then employed to study the delivery of curcumin aerosols into lung airways using a commercial DPI. Curcumin has been implicated to possess high therapeutic potential as an antioxidant, anti-inflammatory and anti-cancer agent. However, efficacy of curcumin treatment is limited because of the low bioavailability of curcumin when ingested. Hence, alternative drug administration techniques, e.g., using inhalable curcumin-aerosols, are under investigation. Based on the present results, it can be concluded that use of a DPI leads to low lung deposition efficiencies because large amounts of drugs are deposited in the oral cavity. Hence, the output of a modified DPI has been evaluated to achieve improved drug delivery, especially needed when targeting the smaller lung airways. This study is the first to utilize CF-PD methodology to simulate drug-aerosol transport and deposition under actual breathing conditions in a whole lung model, using a commercial dry-powder inhaler for realistic inlet conditions.

Polypharmacy in older adults with human immunodeficiency virus infection compared with the general population.

BackgroundThe percentage of older HIV-positive patients is growing, with an increase in age-related comorbidities and concomitant medication.ObjectivesTo quantify polypharmacy and profile types of non-antiretroviral drugs collected at community pharmacies in 2014 by HIV-positive individuals on antiretroviral therapy and to compare these findings with those of the general population.MethodsHIV-positive patients (n=199) were compared with a group of patients from the general population (n=8,172), aged between 50 and 64 years. The factors compared were prevalence of polypharmacy (≥5 comedications with cumulative defined daily dose [DDD] per drug over 180), percentage of patients who collected each therapeutic class of drug, and median duration for each drug class (based on DDD). Results were stratified by sex.ResultsPolypharmacy was more common in HIV-positive males than in the male general population (8.9% vs 4.4%, P=0.010). Polypharmacy was also higher in HIV-positive females than in the female general population (11.3% vs 3.4%, P=0.002). Percentage of HIV-positive patients receiving analgesics, anti-infectives, gastrointestinal drugs, central nervous system (CNS) agents, and respiratory drugs was higher than in the general population, with significant differences between male populations. No differences were observed in proportion of patients receiving cardiovascular drugs. The estimated number of treatment days (median DDDs) were higher in HIV-positive males than in males from the general population for anti-infectives (32.2 vs 20.0, P<0.001) and CNS agents (238.7 vs 120.0, P=0.002). A higher percentage of HIV-positive males than males from the general population received sulfonamides (17.1% vs 1.5%, P<0.001), macrolides (37.1% vs 24.9%, P=0.020), and quinolones (34.3% vs 21.2%, P=0.009).ConclusionPolypharmacy is more common in HIV-positive older males and females than in similarly aged members of the general population. HIV-positive patients received more CNS drugs and anti-infectives, specifically sulfonamides, macrolides, and quinolones, but there were no differences in the percentage of patients receiving cardiovascular drugs. It is essential to investigate nonantiretroviral therapy medication use in the HIV-positive population to ensure these patients receive appropriate management.

Drugs Delivery by Charities: A Possible Epidemiologic Indicator in Children of Undocumented Migrants.

Describing the health status of a population is difficult, especially in the case of irregular migrants who are now a growing population in western Countries. Data for children of these families are almost inexistent. In the absence of databases on this peculiar pediatric population, we analyzed drugs dispensation by a major Charity to have an insight into their health needs. This observational retrospective study was carried out during the entire 2015 and enrolled 628 undocumented children. A cohort of 8438 adult patients belonging to the same ethnic groups was used for comparison. Respiratory drugs were those most commonly prescribed, followed by those for skin and ocular diseases and by those for gastrointestinal disorders. Also in adults respiratory medications were the most dispensed, but almost in equal measure than cardiovascular drugs.To our knowledge this is the first study on the health needs of undocumented children residing in a western Country. The method we used seems to be a useful method for epidemiological analysis. As could be expected, respiratory and skin diseases ranked first, possibly owing to environmental factors.

The effects of inhaled respiratory drugs on the risk of stroke: A nested case-control study

Although there have been concerns that inhaled long-acting muscarinic antagonists increase the risk of stroke, controversies exist. We investigated whether respiratory drugs including long-acting muscarinic antagonists are associated with the risk of stroke. A nested case-control study using the nationwide insurance claims database of the Health Insurance Review and Assessment Service (Seoul, Republic of Korea) was conducted. Overall, 16,354 stroke cases and 74,451 matched (up to 1:5) controls were identified from 809,684 subjects without acute major cardiovascular events in the past year between January 1, 2010, and December 31, 2011. To determine whether the use of inhaled respiratory drugs is associated with the risk of stroke, conditional logistic regression analysis adjusted by comorbidities, cardiovascular drugs and healthcare utilization was performed. After adjusting for covariates, there were no statistically significant effects of the inhaled drugs on stroke incidence, except for inhaled corticosteroids without a long-acting β2-agonists, which was significantly associated with hemorrhagic stroke. Inhaled respiratory medications, including long-acting muscarinic antagonists, did not affect the risk of stroke in the inhaled respiratory drug users.

The impact of adherence to inhaled drugs on 5‐year survival in COPD patients: a time dependent approach

PurposeWhether inhaled medications improve long‐term survival in Chronic Obstructive Pulmonary Disease (COPD) is an open question. The purpose of this study is to assess the impact of adherence to inhaled drug use on 5‐year survival in COPD.MethodsA population‐based cohort study in three Italian regions was conducted using healthcare linked datasets (hospitalization, mortality, drugs). Individuals (45+ years) discharged after COPD exacerbation in 2006–2009 were enrolled. Inhaled drug daily use during 5‐year follow‐up was determined through Proportion of Days Covered on the basis of Defined Daily Doses. Five levels of time‐dependent exposure were identified: (i) long‐acting β2 agonists and inhaled corticosteroids (LB/ICS) regular use; (ii) LB/ICS occasional use; (iii) LB regular use; (iv) LB occasional use; and (v) respiratory drugs other than LB. Cox regression models adjusted for baseline (socio‐demographic, comorbidities, drug use) and time‐dependent characteristics (COPD exacerbations, cardiovascular hospitalizations, cardiovascular therapy) were performed.ResultsA total of 12 124 individuals were studied, 46% women, mean age 73,8 years. Average follow‐up time 2,4 year. A total of 3415 subjects died (mortality rate = 11.9 per 100 person years). In comparison to LB/ICS regular use, higher risks of death for all remaining treatments were found, the highest risk for respiratory drugs other than LB category (HR = 1.63, 95%CI 1.43–1.87). Patients with regular LB use had higher survival than those with LB/ICS occasional use (HR = 0.89, 95%CI 0.79–0.99).ConclusionsThese findings support clinical guidelines and recommendations for the regular use of inhaled drugs to improve health status and prognosis among moderate–severe COPD patients. © 2016 The Authors. Pharmacoepidemiology and Drug Safety Published by John Wiley & Sons Ltd.

The Effect of Spacer Morphology on the Aerosolization Performance of Metered-Dose Inhalers.

Respiratory drug delivery has been attracted great interest for the past decades, because of the high incidence of pulmonary diseases. However, despite its invaluable benefits, there are some major drawbacks in respiratory drug delivery, mainly due to the relatively high drug deposition in undesirable regions. One way to improve the efficiency of respiratory drug delivery through metered-dose inhalers (MDI) is placing a respiratory spacer between the inhaler exit and the mouth. The aim of this study was to assess the effect of type and shape of spacer on the aerosolization performance of MDIs. A commercial Beclomethasone Dipropionate (BDP) MDI alone or equipped with two different spacer devices (roller and pear type) widely distributed in the world pharmaceutical market was used. The effect of spacers was evaluated by calculating aerosolization indexes such as fine particle fraction (FPF), mass median aerodynamic diameters (MMAD) and geometric standard deviation (GSD) using the next generation impactor. Although one of the spacers resulted in superior outcomes than the other one, but it was not statistically significant. The results confirmed that the type and shape of spacer did not substantially influence the aerosolization performance of MDIs.

Respiratory drugs and macrolides prevent asthma exacerbations: A real-world investigation

ObjectiveWe investigated the real-world effectiveness of several drugs (including short- and long-acting beta-agonists [SABAs and LABAs], inhaled corticosteroids [ICS], and antibiotics) in preventing severe asthma exacerbations by carrying-out a large observational study based on the healthcare utilization databases of the Italian Lombardy Region. MethodsWe identified all patients aged 6–40 years who performed an Emergency Department visit for asthma during 2010–2012 as cases. To address bias due to unmeasured confounders, we implemented a case-crossover (CC) design. Addressing other specific sources of systematic errors (e.g. protopathic bias) was of particular concern in this study. ResultsA total of 7300 cases were included in the study. The CC odds ratios (95% confidence intervals) for current vs. past use were 0.81 (0.71, 0.92) for SABAs, 0.83 (0.72, 0.96) for ICS, 0.78 (0.66, 0.91) for LABA/ICS fixed combinations, 0.79 (0.65, 0.97) for other respiratory drugs, and 0.79 (0.69, 0.92) for macrolides antibiotics. Sensitivity analyses showed that our results were robust with respect to several sources of bias. ConclusionsOur study provides evidence from the real-world clinical practice on the effectiveness of several respiratory drugs and macrolides in reducing the risk of severe asthma exacerbations.

Pharmacological Management of Elderly Patients with Asthma-Chronic Obstructive Pulmonary Disease Overlap Syndrome: Room for Speculation?

Asthma and chronic obstructive pulmonary disease (COPD) are two distinct diseases that share a condition of chronic inflammation of the airways and bronchial obstruction. In clinical settings, it is not rare to come across patients who present with clinical and functional features of both diseases, posing a diagnostic dilemma. The overlap condition has been termed asthma-COPD overlap syndrome (ACOS), and mainly occurs in individuals with long-standing asthma, especially if they are also current or former smokers. Patients with ACOS have poorer health-related quality of life and a higher exacerbation rate than subjects with asthma or COPD alone. Whether ACOS is a distinct nosological entity with genetic variants or rather a condition of concomitant diseases that overlap is still a matter of debate. However, there is no doubt that extended life expectancy has increased the prevalence of asthma and COPD in older ages, and thus the probability that overlap conditions occur in clinical settings. In addition, age-associated changes of the lung create the basis for the two entities to converge on the same subject. ACOS patients may benefit from a stepwise treatment similar to that of asthma and COPD; however, the proposed therapeutic algorithms are only speculative and extrapolated from studies that are not representative of the ACOS population. Inhaled corticosteroids are the mainstay of therapy, and always in conjunction with long-acting bronchodilators. The potential heterogeneity of the overlap syndrome in terms of inflammatory features (Thelper-1 vs. T helper-2 pathways) may be responsible for the different responses to treatments. The interaction between respiratory drugs and concomitant diseases should be carefully evaluated. Similarly, the effect of non-respiratory drugs, such as aspirin, statins, and β-blockers, on lung function needs to be properly assessed.

Unintentional Pharmaceutical-Related Medication Errors Caused by Laypersons Reported to the Toxicological Information Centre in the Czech Republic.

The purpose of the article was to study unintentional pharmaceutical-related poisonings committed by laypersons that were reported to the Toxicological Information Centre in the Czech Republic. Identifying frequency, sources, reasons and consequences of the medication errors in laypersons could help to reduce the overall rate of medication errors. Records of medication error enquiries from 2013 to 2014 were extracted from the electronic database, and the following variables were reviewed: drug class, dosage form, dose, age of the subject, cause of the error, time interval from ingestion to the call, symptoms, prognosis at the time of the call and first aid recommended. Of the calls, 1354 met the inclusion criteria. Among them, central nervous system-affecting drugs (23.6%), respiratory drugs (18.5%) and alimentary drugs (16.2%) were the most common drug classes involved in the medication errors. The highest proportion of the patients was in the youngest age subgroup 0-5 year-old (46%). The reasons for the medication errors involved the leaflet misinterpretation and mistaken dose (53.6%), mixing up medications (19.2%), attempting to reduce pain with repeated doses (6.4%), erroneous routes of administration (2.2%), psychiatric/elderly patients (2.7%), others (9.0%) or unknown (6.9%). A high proportion of children among the patients may be due to the fact that children's dosages for many drugs vary by their weight, and more medications come in a variety of concentrations. Most overdoses could be prevented by safer labelling, proper cap closure systems for liquid products and medication reconciliation by both physicians and pharmacists.