Bronchial asthma is one of the much known long-term respiratory conditions. Incidence is increasing, in developing countries like Bangladesh. Cross-sectional type of observational study was carried out over one year (July 2017 to June 2018) in the department of Pharmacology with collaboration of the department of Respiratory Medicine and Medicine, Mymensingh Medical College and Hospital, Mymensingh, Bangladesh. A total of 160 patients were selected non-randomly for the study. Inhalation route (52.35%) was the most preferred one over oral route (47.65%). In total 245 drugs, 131 FDC drugs (Salmeterol + Fluticasone) were prescribed with inhalation therapy which is 53.46%, another 9 FDC drugs that is (Ipratropium bromide + Salbutamol) were prescribed with inhalation therapy which is 3.67%, 101 drugs (Salbutamol) were prescribed with inhalation therapy that is 41.23%, 4 drugs (Beclomethasone) were prescribed with inhalation therapy that is 1.64%. Majority of patient were taking inhalation form of anti-asthmatic drugs.

Early MAXimisation of bronchodilation for improving COPD stability (EMAX) was a large, multicentre, multi-national, randomised, double-blind, 24-week trial. EMAX evaluated the efficacy and safety of dual bronchodilator therapy with umeclidinium bromide (UMEC)/vilanterol (VI) versus monotherapy with either UMEC or salmeterol (SAL) in symptomatic patients with chronic obstructive pulmonary disease (COPD) at low exacerbation risk who were not taking concomitant inhaled corticosteroid (ICS). EMAX generated evidence covering a wide range of patient-centred endpoints in COPD in addition to measures of lung function, clinical deterioration and safety. In addition, prospective and post hoc secondary analyses have generated clinically valuable information regarding the effects of baseline patient characteristics on treatment outcomes. Importantly, as concomitant ICS use was not permitted in this study, EMAX compared dual long-acting muscarinic antagonist (LAMA)/long-acting β2-agonist (LABA) therapy with LAMA or LABA monotherapy without potential confounding due to concurrent ICS use or withdrawal. EMAX demonstrated beneficial treatment effects of UMEC/VI over UMEC or SAL monotherapy as maintenance treatment across a range of different patient characteristics, with no forfeit in safety. Thus, the trial provided novel insights into the role of LAMA/LABA versus LABA and LAMA monotherapies as maintenance therapy for patients with symptomatic COPD at low risk of exacerbations. This article will explore the clinical implications of the main findings to date of the EMAX trial and consider the key learnings this trial offers for future trial design in COPD.

Fluticasone propionate/formoterol fumarate (FP/FORM) is one of the newer combinations among inhaled corticosteroid (ICS) and long-acting β2-agonist (LABA) combination formulations currently available. To evaluate the efficacy and safety of this FP/FORM combination, it is important to review all the available evidence and take a comprehensive look at the current and relevant data in the patient population suffering from asthma and chronic obstructive pulmonary disease (COPD).

Objective: The objective of this study was to evaluate and compare knowledge, attitude, and practice patterns between pulmonologists and allergists for adult asthma in Turkey.Methods: Questionnaire-based data were gathered from 236 pulmonologists and 62 allergists, who had been members of the Turkish Thoracic Society and Turkish National Society of Allergy and Clinical Immunology in January-March 2021. Univariate and multivariate statistics were used to determine the factors associated with primary reliever preferences.Results: Of the 298 physicians, 39% encountered at least five asthma patients daily. Spirometer was used frequently by both the allergists (82.3%) and pulmonologists (77.5%) for asthma diagnosis. Budesonide was the most preferred inhaler corticosteroid. Formoterol/budesonide was the most preferred ICS/LABA combination, followed by beclomethasone/formoterol and fluticasone/salmeterol for asthma treatment. For mild asthmatics, formoterol/ICS was the most preferred (72.6%) reliever among allergists, whereas salbutamol was the most preferred (66.1%) among pulmonologists (p < 0.001). Age and workplace were associated with salbutamol preference of doctors for mild asthmatics. Age, specialty, and patient examination time were significantly associated with salbutamol preference for severe asthmatics.Conclusions: The use of diagnostic tools, such as a spirometer, for asthma diagnosis was compatible with the guidelines. While recent updates of the guidelines indicate that salbutamol should not be used solely in mild asthmatics due to its harmful effects in long-term use, it still was the most preferred drug by pulmonologists. Postgraduate education programs are needed to improve compliance with the guidelines.

Apart from the individual diseases, some patients also show overlapping manifestations of asthma and COPD. Nevertheless, the diagnosis of COPD is often delayed due to inaccessibility to spirometry; the prevalence of the asthma COPD overlap phenotype is rather high given the exposure to biomass smoke. Furthermore, the rates of exacerbations are twice as high compared to the patients with either of the diseases. A treatment strategy that would reduce the risk of exacerbations would contribute immensely to the management of such patients. Evidence of eosinophilia (marker of inflammation) in patients with asthma, asthma COPD overlap phenotype or COPD alone should prompt treatment with a combination of inhaled corticosteroids (ICS)/ long-acting β-agonists (LABA); several studies have shown improvement in the airflow limitation and reduction in the rate of exacerbations with salmeterol-fluticasone combination (SFC). Considering the association of COPD and cardiovascular diseases (CVD), it is critical to determine the cardiovascular safety of the LABA in such patients. Salmeterol is a highly selective partial b-2 agonist; the TORCH study and the studies comparing formoterol and salmeterol infer that there is no increased risk of new cardiovascular adverse events either with Salmeterol or SFC. Furthermore, the combination may provide certain degree of cardio-protection. Since COPD per se increases the risk of CVD, the cardio-safety of salmeterol outweighs its onset of action. SFC has well substantiated benefits in patients with asthma, COPD and high-risk patients such as those with an overlap of COPD and asthma symptoms, patients with elevated eosinophils and pre-existing CVD. An advisory board was hence conducted, which discussed the role of combination of salmeterol and fluticasone (SFC) not only in asthma and COPD but also in asthma COPD overlap phenotype. Based on the panel's clinical experience and the expertise derived thereof, the propositions regarding the place of SFC therapy in patients with stable and uncontrolled asthma, asthma COPD overlap phenotype and COPD has been put forth.

Asthma symptoms can be relieved through a maintenance treatment combining long-acting β2-agonist and inhaled corticosteroids (LABA/ICS). However, for patients with inadequately controlled asthma, the LABA/ICS combination might not be sufficient, and clinical guidelines recommend the administration of inhaled long-acting muscarinic antagonists (LAMA) as an add-on therapy to better control asthma and improve lung function. For nearly two decades, the only LAMA to be approved on the market has been tiotropium.

Background: Wixela Inhub (trademarks of Viatris, Inc.) is a dry powder inhaler (DPI) that delivers a fixed-dose combination of fluticasone propionate and salmeterol and is approved as a generic equivalent to Advair Diskus (trademarks of GlaxoSmithKline plc) for the treatment of asthma and chronic obstructive pulmonary disease (COPD). The dosing performance of DPIs is dependent on the patient's inspiratory capability, which may be impacted in disease populations such as those with severe COPD. The objective of this study was to evaluate the in vitro dose delivery of fluticasone propionate and salmeterol from the Inhub inhaler with in vivo inhalation profiles of severe COPD patients, using two types of breathing simulator with different modes of operation. Materials and Methods: Two breathing simulators (Si-Plan and Copley BRS3100) were used with United States Pharmacopoeia (USP) <601> apparatus 5 (Next Generation Impactor and accessories) to measure the total emitted dose and fine particle mass of fluticasone propionate and salmeterol for Wixela Inhub (250/50 mcg) using 13 severe COPD patient inhalation profiles. Results: Wixela Inhub demonstrated low flow dependency across the range of COPD patient profiles tested (peak inspiratory flow rate 60.8-84.9 L minute-1), when assessed by total emitted dose and fine particle mass. The results were similar to literature results reported for fluticasone propionate from the Diskus inhaler, tested using a proprietary breathing simulator and Andersen Cascade Impactor. Comparison between the breathing simulators showed no significant difference in fluticasone propionate results, but a small difference was observed between the breathing simulators for salmeterol total emitted dose and fine particle mass. Conclusions: This study demonstrates that severe COPD patients are likely to achieve a consistent inhaled dose from Wixela Inhub, with low flow dependency observed within this patient population. In addition, both breathing simulators, which differ significantly in design, produced similar results for fluticasone propionate, but yielded slightly (but statistically significant) different results for salmeterol.

Background: The efficacy of budesonide + formoterol therapy compared with high-dose salmeterol + fluticasone therapy plus short-acting β-agonist (SABA) has not been evaluated specifically in children. Objectives: To evaluate the efficacy and safety of budesonide + formoterol combination therapy two times a day plus as needed compared with salmeterol + fluticasone two times a day plus SABA (as needed) in children in China. Methods: This prospective cohort study included 164 children with persistent asthma (aged 12-17 years) who had experienced a minimum of one asthma exacerbation in 12 months prior to the study. The primary outcome was the time to the first severe exacerbation. Results: Eighty-two children were assigned to each of two groups. The exacerbation rate per 100 patients per year was not found to be significantly different. The number of patients with hospitalization/emergency room therapy was lower in budesonide + formoterol group, but the risk difference was not statistically significant. Asthma control measures showed comparable effects. Both treatments were well-tolerated. Conclusion: No significant differences were observed in the outcome measures between the groups. Budesonide + formoterol therapy is a favorable approach in terms of a low load of ICS, steroid exposure, need for multiple inhalers and cost.

Rationale: Inhaled corticosteroids (ICS) are commonly prescribed with long-acting β2-agonists (LABA) in chronic obstructive pulmonary disease (COPD). To date, the effects of ICS therapy on the airway microbiome in COPD are unknown. Objectives: To determine the effects of ICS/LABA on the airway microbiome of patients with COPD. Methods: Clinically stable patients with COPD were enrolled into a 4-week run-in period during which ICS was discontinued and all participants were placed on formoterol (Form) 12 μg twice daily (BID). The participants were then randomized to budesonide/formoterol (Bud + Form; 400/12 μg BID), fluticasone/salmeterol (Flu + Salm; 250/50 μg BID), or formoterol only (12 μg BID) for 12 weeks. Participants underwent bronchoscopy before and after the 12-week treatment period. The primary endpoint was the comparison of changes in the airway microbiome over the trial period between the ICS/LABA and LABA-only groups. Measurements and Main Results: Sixty-three participants underwent randomization: Bud + Form (n = 20), Flu + Salm (n = 22), and Form (n = 21) groups; 56 subjects completed all visits. After the treatment period, changes in α-diversity were significantly different across groups, especially between Flu + Salm and Form groups (Δrichness: P = 0.02; ΔShannon index: P = 0.03). Longitudinal differential abundance analyses revealed more pronounced microbial shifts from baseline in the fluticasone (vs. budesonide or formoterol only) group. Conclusions: Fluticasone-based ICS/LABA therapy modifies the airway microbiome in COPD, leading to a relative reduction in α-diversity and a greater number of bacterial taxa changes. These data may have implications in patients who develop pneumonia on ICS. Clinical trial registered with www.clinicaltrials.gov (NCT02833480).

This study was to explore the use of convolutional neural network (CNN) for the classification and recognition of computerized tomography (CT) images of chronic obstructive pulmonary disease (COPD) and the therapeutic effect of clarithromycin combined with salmeterol/fluticasone. First, the clinical data of COPD patients treated in hospital from September 2018 to December 2020 were collected, and CT and X-ray images were also collected. CT-CNN and X ray-CNN single modal models were constructed based on the LeNet-5 model. The randomized fusion algorithm was introduced to construct a fused CNN model for the diagnosis of COPD patients, and the recognition effect of the model was verified. Subsequently, the three-dimensional reconstruction of the patient's bronchus was performed using the classified CT images, and the changes of CT quantitative parameters in COPD patients were compared and analyzed. Finally, COPD patients were treated with salmeterol/fluticasone (COPD-C) and combined with clarithromycin (COPD-T). In addition, the differences between patients' lung function indexes, blood gas indexes, St. George respiratory questionnaire (SGRQ) scores, and the number of acute exacerbations (AECOPD) before and after treatment were evaluated. The results showed that the randomized fusion model under different iteration times and batch sizes always had the highest recognition rate, sensitivity, and specificity compared to the two single modal CNN models, but it also had longer training time. After CT images were used to quantitatively evaluate the changes of the patient's bronchus, it was found that the area of the upper and lower lung lobes of the affected side of COPD patients and the ratio of the area of the tube wall to the bronchus were significantly changed. The lung function, blood gas index, and SGRQ score of COPD-T patients were significantly improved compared with the COPD-C group (P < 0.05), but there was no considerable difference in AECOPD (P > 0.05). In summary, the randomized fusion-based CNN model can improve the recognition rate of COPD, and salmeterol/fluticasone combined with clarithromycin therapy can significantly improve the clinical treatment effect of COPD patients.

Despite multiple available fixed-dose combinations (FDCs) of inhaled long-acting β2-agonists (LABAs) plus long-acting muscarinic antagonists (LAMAs) and LABAs plus inhaled corticosteroids (ICS) for COPD, uncertainty remains regarding their comparative effects.

Both asthma and chronic obstructive pulmonary disease (COPD) are inflammatory chronic respiratory conditions with high rates of morbidity and mortality worldwide. The objectives of this review are to briefly describe the pathophysiology and epidemiology of asthma and COPD, discuss guideline recommendations for uncontrolled disease, and review a new generic option for the treatment of asthma and COPD. Although mild forms of these diseases may be controlled with as-needed pharmacotherapy, uncontrolled or persistent asthma and moderate or severe COPD uncontrolled by bronchodilators with elevated eosinophilia or frequent exacerbations may require intervention with combination therapy with inhaled corticosteroids (ICS) and long-acting beta agonists (LABAs), according to international guidelines. Fixed-dose combinations of ICS/LABA are commonly prescribed for both conditions, with fluticasone propionate (FP) and salmeterol forming a cornerstone of many treatment plans. An oral inhalation powder containing the combination of FP and salmeterol has been available as Advair Diskus® in the United States for almost 20 years, and the first and only substitutable generic version of this product has recently been approved for use: Wixela™ Inhub™. Bioequivalence of Wixela Inhub and Advair Diskus has been established. Furthermore, the Inhub inhaler was shown to be robust and easy to use, suggesting that Wixela Inhub may provide an alternative option to Advair Diskus for patients with asthma or COPD requiring intervention with an ICS/LABA.

Rationale: lactose is the only FDA-approved carrier for dry powder inhaler (DPI) formulations in the US. Lactose carrier-based DPI products are contraindicated in patients with a known lactose allergy. Hence, inhaler formulations without lactose will benefit lactose allergic asthmatics. Objectives: to rationally design and develop lactose carrier-free dry powder inhaler formulations of fluticasone propionate and salmeterol xinafoate that will benefit people with known lactose allergy. The study also aims at improving the aerosol deposition of the dry powder formulation through advanced particle engineering design technologies to create inhalable powders consisting of nanoparticles/microparticles. Methods: advanced DPI nanoparticle/microparticle formulations were designed, developed and optimized using organic solution advanced closed-mode spray drying. The co-spray dried (co-SD) powders were comprehensively characterized in solid-state and in vitro comparative analysis of the aerodynamic performance of these molecularly mixed formulations was conducted with the marketed formulation of Advair® Diskus® interactive physical mixture. Measurements and main results: comprehensive solid-state physicochemical characterization of the powders showed that the engineered co-SD particles were small and spherical within the size range of 450 nm to 7.25 μm. Improved fine particle fraction and lower mass median aerodynamic diameter were achieved by these DPI nanoparticles/microparticles. Conclusions: this study has successfully produced a lactose-free dry powder formulation containing fluticasone propionate and salmeterol xinafoate with mannitol as excipient engineered as inhalable DPI nanoparticles/microparticles by advanced spray drying. Further, co-spray drying with mannitol and using Handihaler® device can generate higher fine particle mass of fluticasone/salmeterol. Mannitol, a mucolytic agent and aerosol performance enhancer, is a suitable excipient that can enhance aerosol dispersion of DPIs.

Background: A generic combination of fluticasone propionate and salmeterol xinafoate inhalation powder in a premetered, multidose, nonreusable inhaler was recently approved. Objective: To assess the performance of the generic device. Methods: Findings from three studies with regard to device usability, function, and robustness were reviewed. Results: In a study to assess device function in patients and healthy volunteers, the generic device was successfully used by patients with asthma and chronic obstructive pulmonary disease who were either dry powder inhaler users or dry powder inhaler-naive, even though they were not trained beyond being provided the instructions for use. In a study to measure inhaled flow rates generated by patients and healthy volunteers, the generic device consistently simulated the delivery of a full dose of drug, even to patients with severe respiratory disease and reduced inspiratory flow rates. Although the generic device had a slightly higher airflow resistance, this study demonstrated that this difference did not result in any clinically meaningful differences in terms of drug delivery. Pressure drop, a key parameter that drives the fluidization and aerosolization of the powder dose, was found to be comparable between the devices. In an open-label study, the generic device met all U.S. Food and Drug Administration specifications for device robustness after 21.5 days of twice-daily dosing via oral inhalation among 111 participants with asthma or chronic obstructive pulmonary disease. All inhalers tested demonstrated conformity with a pharmacopeia with respect to key quality parameters (assay, delivered dose uniformity, aerodynamic size distribution). There was no evidence of chemical degradation of the active ingredients, nor of microbial or water ingress into the powder, as a result of inhaler use.

Összefoglaló. Az allergiás betegségekben szenvedő emberek száma világszerte, köztük Magyarországon is növekszik. Az egészségügyi ellátórendszerek azon dolgoznak, hogy minél hatékonyabban tudják felhasználni a rendelkezésre álló forrásokat. Az Allergic Rhinitis and its Impact on Asthma (ARIA) szervezet célja az allergiás náthában szenvedő betegek ellátásának javítása, szakmai ajánlások készítése, aktualizálása. Ennek egyik módja integrált betegellátási utak kidolgozása. Célunk ezek hazai elérhetővé tétele, az ajánlások széles körű elterjesztése az Európai Unió (EU) többi tagállamához hasonlóan Magyarországon is. Az ARIA más nemzetközi innovatív szervezetek bevonásával olyan integrált betegellátási utakat fejlesztett ki, amelyek allergiás nátha, esetleg társbetegsége, az asztma esetén támogatják a kezelést. Ezeket újgenerációs irányelvek kidolgozása útján alkották, amelyekhez felhasználták a mobiltechnológiából és pollenkamra-vizsgálatokból származó valós evidenciákat is. A gyógyszeres terápia optimalizálásához a vizuális analóg skálán alapuló, úgynevezett Mobil Légúti Figyelő Hálózat algoritmusát digitalizálták, és valós evidenciák felhasználásával tovább finomították. Allergén immunterápiára az ARIA a világon elsőként dolgozott ki integrált betegellátási utakat 2019-ben. A kezelési irányelvekhez való adherenciaszint alacsony, a betegek a tüneteik erőssége alapján módosítják a kezelést. A flutikazon-propionát-azelasztin kombináció hatása erősebb az intranasalis kortikoszteroidokénál, míg az utóbbi hatásosabb az oralis H1-antihisztaminoknál. A mobiltelefonokban tárolt elektronikus napló vagy más 'mobile health' (mHealth) eszközök használata segíti a betegek kiválasztását allergén immunterápiára. Az ARIA által javasolt algoritmus megfelelőnek mutatkozott az allergiás rhinitis kezelésére, ezért ezek az irányelvek bekerülnek integrált betegellátási utakba, és részét fogják képezni az EU Egészségügyi és Élelmiszer-biztonsági Főigazgatósága digitalizált, személyközpontú gondozási anyagainak. Az allergén immunterápia hatékony az inhalatív allergének által okozott allergiás betegségekben, alkalmazását azonban korlátozni kell gondosan válogatott betegekre. Orv Hetil. 2020; 161(49): 2059-2071. Summary. The number of allergic patients is increasing all over the world, also in Hungary. Delivering effective and cost-effective health care is essential for all health care systems. ARIA (Allergic Rhinitis and its Impact on Asthma) aims to improve the care of patients who suffer from allergic rhinitis by setting up guidelines and updating them. Development of ICPs (integrated care pathways) can play an essential role in attaining this goal. Our aim is to make ICP-s developed by ARIA available also in Hungary, as is already the case in other countries of the European Union (EU). Together with other international initiatives, ARIA has worked out digitally-enabled ICPs to support care in allergic rhinitis and comorbid asthma. ICPs are based on new-generation guidelines using RWE (real-world evidence) from chamber studies and mobile technology. The MASK (Mobile Airways Sentinel NetworK) algorithm - based on visual analogue scale - was digitalized to support pharmacotherapy, and was refined by using RWE. ARIA was the first to develop ICPs for allergen immunotherapy (AIT) in 2019. Based on MASK data, patients did not follow guidelines and their adherence to treatment was poor. Patients would modify their treatments, depending on the disease control. The effect of fluticasone propionate-azelastine combination is superior to intranasal corticosteroids which are superior to oral H1-antihistamines. Electronic diaries obtained from cell phones and other 'mobile health' (mHealth) devices help select patients for AIT. The ARIA algorithm for AR was found appropriate and no change is necessary. These guidelines will inform ICPs and will be included in the DG Santé digitally-enabled, person-centred care system. AIT is an effective treatment for allergic diseases caused by inhaled allergens. Its use should, however, be restricted to carefully selected patients. Orv Hetil. 2020; 161(49): 2059-2071.

This exploratory, randomised, double-blind, double-dummy, multicentre, cross-over study explored the effect of 6 weeks of treatment with tiotropium/olodaterol (T/O) versus fluticasone propionate/salmeterol (F/S) on left ventricular filling in patients with chronic obstructive pulmonary disease with functional residual capacity (FRC) >120% predicted and postbronchodilator improvement of FRC ≥7.5%. Overall, 76 patients were randomised across nine sites. Treatment with T/O or F/S increased left ventricular end-diastolic volume index from baseline (adjusted mean change: T/O: 2.317 mL/m2, F/S: 2.855 mL/m2), with no statistically significant difference between treatments. However, T/O resulted in a significantly greater reduction in lung hyperinflation versus F/S (FRC plethysmography absolute change from baseline: F/S: -0.329 L, T/O: -0.581 L).