Thoughtful prescription of inhaled medication has the potential to reduce inhaler-related greenhouse gas emissions by 85.

INTRODUCTION: Both physicians and patients are increasingly aware of the environmental impacts of medication. The shift of treatment paradigm towards MART-treatment (Maintenance and Reliever Therapy) in asthma affects the treatment-related emissions. The carbon footprint of inhaled medication is also tied to the type of the device used. Today the most commonly used propellant-containing pressurised metered-dose inhalers (pMDIs) have a carbon footprint typically 20-40-fold higher than propellant-free dry powder inhalers (DPIs) and soft mist inhalers. METHODS: We analysed the carbon footprint of inhaled medications in Europe using published life cycle analyses of marketed inhalers and comprehensive 2020 European sales data. In addition, we give an estimate on treatment-related emissions of different treatment regimens on Global Initiative for Asthma (GINA) step 2. RESULTS: There is potential to reduce the carbon footprint of inhaled medications by 85% if DPIs are preferred over pMDIs. Emissions from pMDIs in the EU were estimated to be 4.0 megatons of carbon dioxide equivalent (MT CO2e) and this could be reduced to 0.6 MT CO2e if DPIs were used instead. In the treatment of moderate asthma with DPI, an as-needed combination of inhaled corticosteroid and long-acting beta-agonist in a single inhaler had a substantially lower annual carbon footprint (0.8 kg CO2e) than the more traditional maintenance therapy with an inhaled corticosteroid alone with as-needed short-acting beta-agonist (2.9 kg CO2e). DISCUSSION: There has been an urgent call for healthcare to reduce its carbon footprint for appropriate patients with asthma and chronic obstructive pulmonary disease (COPD), changing to non-propellant inhalers can reduce the carbon footprint of their treatment by almost 20-fold.

Risk of neuropsychiatric adverse events associated with montelukast use in children and adolescents: a population-based case-crossover study.

PURPOSE: Montelukast is used extensively in children and adolescents for allergic rhinitis and asthma. However, concerns have been raised regarding the increased risk of neuropsychiatric adverse events (NPAEs) associated with montelukast use. Therefore, our case-crossover study was conducted to observe whether there is an increased risk of NPAEs associated with montelukast use in children and adolescents. MATERIALS AND METHODS: A population-based case-crossover study using the customised Health Insurance Review and Assessment (HIRA) dataset was conducted. Paediatric patients aged between 0 and 19 years diagnosed with allergic rhinitis and/or asthma with a history of at least one montelukast prescription between 1 January 2018 and 31 December 2021 were included. Exposure to montelukast was assessed during 3-, 7-, 14-, 28- and 56-day hazard periods prior to each patient's NPAE. Stratified analyses according to age group, gender and season for the risk of NPAEs associated with montelukast use in the previous 7 days and 14 days were performed, respectively. Conditional logistic regression analysis was used to calculate adjusted ORs (aORs) with their corresponding 95% CIs, adjusting for concomitant medications. RESULTS: A total of 161 386 paediatric patients was identified. An increased risk of NPAEs associated with montelukast was found in all time window periods, including 3-day (aOR 1.28, 95% CI 1.24 to 1.32), 7-day (aOR 1.29, 95% CI 1.26 to 1.33), 14-day (aOR 1.34, 95% CI 1.31 to 1.37), 28-day (aOR 1.38, 95% CI 1.36 to 1.41) and 56-day (aOR 1.21, 95% CI 1.19 to 1.22) preceding hazard periods compared with use in the four control periods. CONCLUSION: Children and adolescents with allergic rhinitis and/or asthma should be prescribed montelukast with caution considering clinical benefits.

Preparation and In Vitro Evaluation of Montelukast Sodium-Loaded 3D Printed Orodispersible Films for the Treatment of Asthma.

This research aims to produce orodispersible films (ODFs) and determine their potential use in the oral delivery of montelukast sodium for asthma treatment and allergic rhinitis. ODFs were successfully developed by Three-dimensional (3D) printing using propylene glycol (PG), and hydroxypropyl methylcellulose (HPMC), polyethylene glycol 400 (PEG). Finally, the amount of montelukast sodium in the ODFs was 5% (w/w). Drug-excipients compatibility with Fourier Transformed Infrared (FTIR) spectroscopy, mass uniformity, thickness, disintegration time, folding endurance, moisture absorption, pH, in vitro drug release (dissolution), drug content, moisture loss, moisture content, mechanical properties, and cytotoxicity studies were performed on the prepared films. All formulations disintegrated in approximately 40 s. Over 98% of drug release from all films within 2 min was confirmed. It was reported that Fm1-4 (8% HPMC and 1% PEG) and Fm2-4 (10% HPMC and 3% PEG) are more suitable for drug content, but Fm2-4 may be the ideal formulation considering its durability and transportability properties. Based on the characterization results and in vitro release values, the montelukast sodium ODF can be an option for other dosage forms. It was concluded that the formulations did not show toxic potential by in vitro cytotoxicity study with 3T3 cells. This new formulation can efficiently treat allergic rhinitis and asthma diseases.

Antiasthmatic Medicinal Plants of Tanzania: An Ethnomedicinal and Ethnopharmacological Review.

Traditional medicinal plants (TMPs) are a significant part of people's quality of life, offering a natural substitute for modern drugs with numerous side effects. In Tanzania, data on antiasthmatic TMPs are highly fragmented. This review, a comprehensive compilation of ethnobotanical research evidence, aimed to provide a thorough understanding of TMPs used by the locals for asthma management and identify species that have already been investigated in preclinical studies. The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. To gather relevant literature on antiasthmatic TMPs used by Tanzanians, a web search using electronic databases (Scopus, PubMed, ProQuest, Academic Library, Web of Science, SciFinder, Wiley Online Library, Google Scholar, ScienceDirect, and African Journals Online) was conducted. The scientific names were verified through the Plants of the World Online database, and the collected information was analysed for descriptive statistics using Microsoft Excel software. The ethnomedicinal information was obtained from 24 different articles. Microsoft Excel software was used to analyse the data using descriptive statistics. A total of 62 TMPs belonging to 33 families were identified. Species of the Fabaceae (14.5%) and Rubiaceae families (8.1%) are the most utilized. The analysis revealed that trees (42.0%) and leaves (40.0%) are the most utilized life forms and plant parts, respectively. Most plant materials (59.7%) used to make remedies were collected from the wild environment. Decoction (55.0%) is the dominant preparation method of remedies, and the majority (69.0%) were orally administered. Of the recorded TMPs, 22.6% had their in vivo antiasthmatic activity reported in the literature. The review also highlighted the strategic significance of preparations of remedies made from TMPs for discovering and developing new antiasthmatic drugs. However, the need to identify the molecular targets of action and toxicological aspects of the TMPs should be considered.

[Severe asthma: Pathophysiology, diagnosis, and treatment]. / Asma grave: fisiopatología, diagnóstico y tratamiento.

Severe asthma is an entity with a complex diagnosis, requiring an adequate differential diagnosis and identification of endotypes for a correct approach and therapeutic process. In the present review, we show a synthesis of the current literature on the diagnosis, pathophysiology, and management of severe asthma, having critically analyzed the evidence in search engines such as Medline, Scopus, and Embase.

El asma grave es una enfermedad compleja, que requiere un enfoque y diagnóstico diferencial ordenado e identificación de endotipos para el correcto abordaje y tratamiento. El tratamiento farmacológico cuenta cada vez con más moléculas a disposición del personal médico para el control efectivo de los síntomas. Esta revisión muestra una síntesis de la bibliografía actual acerca del diagnóstico, fisiopatología y tratamiento del asma grave, mediante la lectura crítica previa de la evidencia científica en buscadores como Medline, Scopus y Embase.

Anti-astmatic effect of ROCK inhibitor, GSK429286 A, in experimentally induced allergic airway inflammation.

BACKGROUND: Allergic asthma is a chronic inflammatory disease characterized by airway hyperresponsiveness, inflammation and remodeling. ROCK inhibitors have now been shown to have the potential to alleviate these symptoms, although the specific effects of a new ROCK inhibitor, GSK429286 A, remain underexplored. OBJECTIVE: The aim of this study was to evaluate the therapeutic effects of a novel ROCK inhibitor, GSK429286 A, which exhibits a high affinity for both ROCK1 and ROCK2 isoforms, on allergic asthma in a guinea pig model, focusing on its effects on airway hyperresponsiveness, inflammation, and remodeling. METHODS: To induce allergic asthma, guinea pigs were sensitized with ovalbumin for 28 days, and in the middle of sensitization they were treated with different doses of the RoCK inhibitor, GSK429286 A. The study evaluated the effect of the administered doses on the reduction of airway hyperresponsiveness, by measuring specific airway resistance (sRaw), and the number of coughs after citric acid inhalation. We also monitored the anti-inflammatory effect by measuring levels of inflammatory cytokines, IL-2, IL-4, IL-5, IL-13, and remodeling markers, such as collagen deposition, and goblet cell hyperplasia. In addition, we monitored the possible anti-remodeling effect of GSK429286 A by histopathological examination. RESULTS: The ROCK inhibitor, GSK429286 A, showed an effect on suppressing airway hyperresponsiveness by reducing sRaw and the number of coughs in treated guinea pigs compared to controls. Our investigated drug suppressed the release of key mediators of inflammation, including IL-2, IL-4, and IL-5, thus demonstrating the effect of this ROCK inhibitor on the suppression of inflammation in the airways. Finally, GSK429286 A reduced markers of airway remodeling such as collagen deposition and goblet cell hyperplasia. CONCLUSION: GSK429286 A, an inhibitor of the ROCK pathway, exhibits significant anti-inflammatory and antiremodeling effects in a guinea pig model of allergic asthma. Indeed, we demonstrate its effect on suppressing airway hyperreactivity and reducing cough frequency. These findings suggest that GSK429286 A may be a promising therapeutic agent for allergic asthma, although further studies are needed to investigate its long-term efficacy, underlying mechanisms, and optimal dosing strategy.

Real world prescription of beta-blockers in patients with asthma.

PURPOSE: This study aimed to investigate the prescription of beta-blockers (ß-blockers) for patients with asthma. METHODS: In this retrospective cross-sectional study using the National Patient Sample (NPS) of the Health Insurance Review and Assessment Service (HIRA) of South Korea, ß-blockers and asthma medications were investigated using generic name codes provided by HIRA. Concomitant administration was identified when a ß-blocker and an asthma medication were co-prescribed in one billing statement or when separate ß-blocker and asthma prescriptions had overlapping dates of use. RESULTS: In the 1027 patients with asthma who were prescribed non-selective ß-blockers (non-SBs), 3087 non-SB prescriptions were identified, of which 62.3% and 37.3% were for carvedilol and propranolol, respectively. Of the 906 patients with asthma prescribed selective ß-blockers (SBs), 2942 SB prescriptions were identified, of which 48.5%, 28.3%, and 20.3% were for bisoprolol, atenolol, and nebivolol, respectively. Overall, 2149 non-SB and 2124 SB prescriptions with overlapping use dates with asthma medications were identified, which were prescribed to 726 and 657 patients, accounting for 70.7% and 72.5% of the patients receiving non-SBs and SBs, respectively. ß2-agonists accounted for 39.9% of the concomitant asthma medications with overlapping dates of use with non-SBs. Co-prescribing of bronchodilators occurred at a rate of 38.7% and 45.1% for the 3087 non-SB prescriptions and 2942 SB prescriptions, respectively. CONCLUSIONS: Carvedilol and propranolol accounted for half of all ß-blockers prescribed to asthma patients. Prescribing ß-blockers to patients with asthma requires caution to prevent exacerbation of asthma and drug interactions between ß-blockers and co-prescribed asthma medications.

Efficacy and safety of a proposed omalizumab biosimilar compared to the reference product in the management of uncontrolled moderate-to-severe allergic asthma: a multicenter, phase III, randomized, double-blind, equivalency clinical trial.

Background and aims: Allergic asthma has a considerable burden on the quality of life. A significant portion of moderate-to-severe allergic asthma patients need omalizumab, an anti-immunoglobulin-E monoclonal antibody, as an add-on therapy. In this phase III clinical trial P043 (Zerafil®, CinnaGen, Iran) efficacy, safety, and immunogenicity were compared with Xolair® (the originator omalizumab). The primary outcome was the rate of protocol-defined asthma exacerbations. Methods: Exacerbation rates, Asthma Control Test (ACT) results, spirometry measurements, immunogenicity, and safety were evaluated. Each subject received either medication with a dose ranging from 150 to 375 mg based on pre-treatment serum total IgE level (IU/mL) and body weight (kg) every two or four weeks for a duration of 28 weeks. Results: Exacerbation rates were 0.150 (CI: 0.079-0.220) in the P043 group, and 0.190 (CI: 0.110-0.270) in the omalizumab group (per-protocol). The least squares mean differences of predicted Forced Expiratory Volume in the First second (FEV1) were -2.51% (CI: -7.17-2.15, P=0.29) and -3.87% (CI: -8.79-1.04, P=0.12), pre- and post-bronchodilator use. The mean ± SD of ACT scores at the screening and the last visit were 10.62 ± 2.93 and 20.93 ± 4.26 in P043 and 11.09 ± 2.75 and 20.46 ± 5.11 in the omalizumab group. A total of 288 adverse events were reported for the 256 enrolled participants. Among all, "dyspnea" and "headache" were the most reported ones. The overall incidence of adverse events (P=0.62) and serious adverse events (P=0.07) had no significant differences between the two groups. None of the samples were positive for anti-drug antibodies. Conclusion: P043 was equivalent to omalizumab in the management of asthma in reduction of exacerbations. There was no significant difference in other efficacy and safety parameters. Clinical trial registration: www.clinicaltrials.gov (NCT05813470) and www.IRCT.ir (IRCT20150303021315N20).

Intersocietal survey on real-world asthma management in Italian children.

Pediatric asthma management is a compelling challenge for every pediatrician. Different aspects require attention and definition. The present Intersocietal Survey aimed to collect real-world experiences from a sample of Italian pediatricians. A web platform was used to collect anonymous answers to the survey questions.Four hundred four pediatricians participated in this initiative promoted by the Italian Society of Pediatric Allergy and Immunology (SIAIP), the Society of Preventive and Social Pediatrics (SIPPS), and the Federation of Italian Pediatricians (FIMP).The results showed an extensive participation of primary care pediatricians (72%). There was a large consensus about diagnostic criteria and medication choice. However, treatment duration and device choice were various. Adherence to guidelines on general aspects of practical clinical management was high.In conclusion, the present Intersocietal Survey confirmed that pediatric asthma management is rather satisfactory, even if further improvement should concern a more widespread use of ICS for acute asthma/wheezing attacks, a better definition of the duration of ICS and bronchodilator use, and hospital-primary care integration.

SURFACTANT PROTEIN A: AN INNATE IMMUNE MODULATOR AND THERAPEUTIC IN ASTHMA.

Surfactant Protein A (SP-A) is an innate immune modulator produced by the lung with known protective effects against bacteria and viruses. Its role in asthma, an inflammatory lung disease that affects 10% of the world's population, is not entirely known. In this review, we demonstrate that SP-A confers protection against exposure to interleukin-13, a type 2 cytokine integral to eosinophilic asthma, in a mouse model of SP-A deficiency, a house dust mite model of asthma, and in human bronchial epithelial cells from participants with asthma. We also show that small peptides derived from SP-A, such as the major allele of single nucleotide polymorphism (SNP) rs1965708, which includes the carbohydrate recognition domain of SP-A2 at position 223, reduce airway hyperresponsiveness, airway eosinophils, and mucus in a mouse model of asthma. These data suggest that SP-A has beneficial effects relevant to asthma and that an SP-A peptide may have a new therapeutic use in asthma.

Exploring the In Vitro and In Vivo Therapeutic Efficacy of Juniperus oxycedrus Cade Oil: Antioxidant, Anti-inflammatory, and Anti-asthmatic Effects in an Allergic Asthma Model.

This investigation aimed to explore the antioxidant, anti-inflammatory effects of Cade oil and its efficacy within a Wistar allergic asthma model. The antioxidant activity was assessed through various in vitro tests using chain-breaking antioxidant effects (radical scavenging and reducing abilities assays).  In vivo experiments involved Wistar rats categorized into four groups: negative control group, Ovalbumin-sensitised/challenged group, Cade oil-treated group, and Ovalbumin-sensitised/challenged Cade oil-treated group. These experiments aimed to evaluate oxidative stress parameters in the lungs and erythrocytes. The results indicated that the Cade oil exhibited significant antioxidant capabilities, evidenced by its radical scavenging activity against DPPH, ABTS, and Galvinoxyl radicals, with IC50 values ranging from 21.92 to 24.44 µg/mL. Besides, the reducing abilities methods showed A0,5 value ranging from 11.51 to 30.40  µg/mL for reducing power, Cupric ion reducing antioxidant capacity, and O-phenanthroline assays. Additionally, the IC50 value for ß-carotene scavenging was found to be (8.2 ± 0.25 µg/ml). Analysis revealed high levels of polyphenols and flavonoids in Cade oil, indicating rich polyphenol (275.21 ± 3.14 mg GAE/g DW) and flavonoid (28.23 ± 1.91 µg QE/mg) content. In vivo findings highlighted Cade oil's efficacy in reducing inflammatory cell recruitment, enhancing antioxidant status, reducing lipid peroxidation, and improving histopathological alterations within the allergic asthma model. These results demonstrated that Cade oil has a potent antioxidant, anti-inflammatory, and anti-asthmatic properties, suggesting its potential therapeutic application in asthma treatment.

SingleNucleotide Polymorphisms as Biomarkers of Mepolizumab and Benralizumab Treatment Response in Severe Eosinophilic Asthma.

The most promising treatment options for severe uncontrolled asthma (SUA) have emerged in recent years with the development of monoclonal antibodies for blocking selective targets responsible for the underlying inflammation, such as mepolizumab and benralizumab. However, there is variability in treatment response that is not fully controlled. The variability of the response to mepolizumab and benralizumab could be influenced by single-nucleotide polymorphisms (SNPs), and it would be useful to detect these and use them as predictive biomarkers of response. We conducted a retrospective observational cohort study of 72 Caucasian patients recruited from a tertiary hospital with severe uncontrolled eosinophilic asthma treated with mepolizumab and benralizumab. Polymorphisms in the IL5 (rs4143832, rs17690122), RAD50 (rs11739623, rs4705959), IL1RL1 (rs1420101, rs17026974, rs1921622), GATA2 (rs4857855), IKZF2 (rs12619285), FCGR2A (rs1801274), FCGR2B (rs3219018, rs1050501), FCGR3A (rs10127939, rs396991), FCER1A (rs2251746, rs2427837), FCER1B (rs1441586, rs573790, rs569108), and ZNF415 (rs1054485) genes were analyzed by real-time polymerase chain reaction (PCR) using Taqman probes. The response was analyzed after 12 months of treatment. In patients under mepolizumab treatment, a treatment response defined as a reduction in exacerbations was associated with ZNF415 rs1054485-T (p = 0.042; OR = 5.33; 95% CI = 1.06-30.02), treatment response defined as a reduction in oral corticosteroids use was associated with the number of exacerbations in the previous year (p = 0.029; OR = 3.89; 95% CI = 1.24-14.92), and treatment response defined as improvement in lung function was associated with the age at the beginning of biological therapy (p = 0.002; OR = 1.10; 95% CI = 1.04-1.18), FCER1B rs569108-AA (p < 0.001; OR = 171.06; 95% CI = 12.94-6264.11), and FCER1A rs2427837-A (p = 0.021; OR = 8.61; 95% CI = 1.71-76.62). On the other hand, in patients under benralizumab treatment, treatment response, defined as a reduction in exacerbations, was associated with ZNF415 rs1054485-T (p = 0.073; OR = 1.3 × 108; 95% CI = 1.8 × 10-19-NA), FCER1B rs569108-AA (p = 0.050; OR = 11.51; 95% CI = 1.19-269.78), allergies (p = 0.045; OR = 4.02; 95% CI = 1.05-16.74), and sex (p = 0.028; OR = 4.78; 95% CI = 1.22-20.63); and treatment response defined as improvement in lung function was associated with polyposis (p = 0.027; OR = 9.16; 95% CI = 1.58-91.4), IKZF2 rs12619285-AA (p = 0.019; OR = 9.1; 95% CI = 1.7-75.78), IL5 rs4143832-T (p = 0.017; OR = 11.1; 95% CI = 1.9-112.17), and FCER1B rs1441586-C (p = 0.045; OR = 7.81; 95% CI = 1.16-73.45). The results of this study show the potential influence of the studied polymorphisms on the response to mepolizumab and benralizumab and the clinical benefit that could be obtained by defining predictive biomarkers of treatment response.

Therapeutic effect of long-acting muscarinic antagonist for treating uncontrolled asthma assessed using impulse oscillometry.

BACKGROUND: In recent years, the incorporation of LAMAs into asthma therapy has been expected to enhance symptom control. However, a significant number of patients with asthma continue to experience poorly managed symptoms. There have been limited investigations on LAMA-induced airway alterations in asthma treatment employing IOS. In this study, we administered a LAMA to patients with poorly controlled asthma, evaluated clinical responses and respiratory function, and investigated airway changes facilitated by LAMA treatments using the IOS. METHODS: Of a total of 1282 consecutive patients with asthma, 118 exhibited uncontrolled symptoms. Among them, 42 switched their treatment to high-dose fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) (ICS/LABA/LAMA). The patients were then assessed using AHQ-33 or LCQ and ACT. Spirometry parameters (such as FEV1 or MMEF) and IOS parameters (such as R20 or AX) were measured and compared before and after exacerbations and the addition of LAMA. RESULTS: Of the 42 patients, 17 who switched to FF/UMEC/VI caused by dyspnea exhibited decreased pulmonary function between period 1 and baseline, followed by an increase in pulmonary function between baseline and period 2. Significant differences were observed in IOS parameters such as R20, R5-R20, Fres, or AX between period 1 and baseline as well as between baseline and period 2. Among the patients who switched to inhaler due to cough, 25 were classified as responders (n = 17) and nonresponders (n = 8) based on treatment outcomes. Among nonresponders, there were no significant differences in spirometry parameters such as FEV1 or PEF and IOS parameters such as R20 or AX between period 1 and baseline. However, among responders, significant differences were observed in all IOS parameters, though not in most spirometry parameters, between period 1 and baseline. Furthermore, significant differences were noted between baseline and period 2 in terms of FEV1, %MMEF, %PEF, and all IOS parameters. CONCLUSION: ICS/LABA/LAMA demonstrates superiority over ICS/LABA in improving symptoms and lung function, which is primarily attributed to the addition of LAMA. Additionally, IOS revealed the effectiveness of LAMA across all airway segments, particularly in the periphery. Hence, LAMA can be effective against various asthma phenotypes characterized by airway inflammation, even in real-world cases.