Treatable traits and exacerbation risk in patients with uncontrolled asthma prescribed GINA step 1-3 treatment: A nationwide asthma cohort study.

BACKGROUND AND OBJECTIVE: Uncontrolled asthma in patients treated for mild/moderate disease could be caused by non-pulmonary treatable traits (TTs) that affect asthma control negatively. We aimed to identify demographic characteristics, behavioural (smoking) and extrapulmonary (obesity, comorbidities) TTs and the risk for future exacerbations among patients with uncontrolled asthma prescribed step 1-3 treatment according to the Global Initiative for Asthma (GINA). METHODS: Twenty-eight thousand five hundred eighty-four asthma patients (≥18 y) with a registration in the Swedish National Airway Register between 2017 and 2019 were included (index-date). The database was linked to other national registers to obtain information on prescribed drugs 2-years pre-index and exacerbations 1-year post-index. Asthma treatment was classified into step 1-3 or 4-5, and uncontrolled asthma was defined based on symptom control, exacerbations and lung function. RESULTS: GINA step 1-3 included 17,318 patients, of which 9586 (55%) were uncontrolled (UCA 1-3). In adjusted analyses, UCA 1-3 was associated with female sex (OR 1.34, 95% CI 1.27-1.41), older age (1.00, 1.00-1.00), primary education (1.30, 1.20-1.40) and secondary education (1.19, 1.12-1.26), and TTs such as smoking (1.25, 1.15-1.36), obesity (1.23, 1.15-1.32), cardiovascular disease (1.12, 1.06-1.20) and depression/anxiety (1.13, 1.06-1.21). Furthermore, UCA 1-3 was associated with future exacerbations; oral corticosteroids (1.90, 1.74-2.09) and asthma hospitalization (2.55, 2.17-3.00), respectively, also when adjusted for treatment step 4-5. CONCLUSION: Over 50% of patients treated for mild/moderate asthma had an uncontrolled disease. Assessing and managing of TTs such as smoking, obesity and comorbidities should be conducted in a holistic manner, as these patients have an increased risk for future exacerbations.

Concordance of provider chart notation and guideline-based classification of asthma severity.

OBJECTIVE: To evaluate concordance of asthma severity classification via physician chart notation compared with guideline-based criteria in adolescents with diagnosed asthma. METHODS: Of 284 urban primary care and subspecialty clinic patients aged 13-18 years approached through convenience sampling, 203 surveys were completed (RR = 71.5%). We assessed concordance with sensitivity, specificity, and positive predictive values; overall agreement was evaluated with weighted kappa coefficients and McNemar's test. RESULTS: When considering prescribed treatment according to NAEPP guidelines as a gold standard, the sensitivity for chart notation was very good for intermittent (95%) and less for non-intermittent severity ratings (51%, 58%, and 67% for moderate, severe, and mild persistent asthma, respectively). Overall agreement between chart notation and guideline-based asthma criteria ranged from fair-to-good for mild- (k = 0.36), moderate- (k = 0.44), and severe-persistent severity (k = 0.66). Although the agreement for intermittent severity was highest (k = 0.88), it did not significantly differ by between the two classifications (p ≥ 0.05). CONCLUSIONS: Concordance for all non-intermittent asthma severity classifications varied between physician and medication-driven 2007 NAEPP guideline classifications in an ethnically diverse urban adolescent patient sample. Physicians should remain aware of the potential for this discordance and refer to the guidelines to classify and treat adolescents with asthma.

Uncontrolled asthma in school-aged children-a nationwide specialist care study.

Background: Uncontrolled asthma (UCA) is different from severe asthma and can be identified in children across all ranges of prescribed treatment. Objective: Our aim was to characterize uncontrolled childhood asthma in pediatric specialist care. Methods: We performed a nationwide cross-sectional study of 5497 children (aged 6-17 years) with asthma who were treated by pediatricians at outpatient clinics during 2019 and registered in the Swedish National Airway Register. UCA was defined as an Asthma Control Test score of 19 or lower and/or 2 or more exacerbations in the past year and/or an FEV1 value less than 80% predicted. Treatment was categorized from step 1 to step 5 according to the Global Initiative for Asthma. Results: UCA was identified in 1690 children (31%), of whom 64% had an Asthma Control Test score of 19 or lower, 20% had recurrent exacerbations, and 31% had an FEV1 value less than 80% predicted. UCA was associated with female sex (odds ratio [OR] = 1.29 [95% CI = 1.15-1.45]), older age (OR = 1.02 [95% CI = 1.00-1.04]), obesity (OR = 1.43 [95% CI = 1.12-1.83]), and more treatment using steps 1 and 2 as a reference (step 3, OR = 1.28 [95% CI = 1.12-1.46]); steps 4-5, OR = 1.32 [95% CI = 1.10-1.57]). UCA in children prescribed treatment steps 1 and 2 (group UCA1-2) occurred in 28% of all children at this treatment step (n = 887). Children in group UCA1-2 had exacerbations more frequently than did those children with UCA who were prescribed steps 4 and 5 treatment (24% vs 15% [P = .001]). Conclusion: UCA was common and associated with female sex, increasing age, obesity, and higher Global Initiative for Asthma treatment step. Surprisingly, UCA was also common in children prescribed less than the maximum treatment, and those children could be considered undertreated patients.

Mild asthma: Conundrums, complexities and the need to customize care.

Mild and moderate asthma cover a wide range of asthma presentations, phenotypes and symptom burden, and account for the majority of people with asthma worldwide. Mild asthma has been difficult to define because of its heterogeneity and wide spectrum of impact and outcomes, including being associated with severe exacerbations. Assessment of mild-moderate asthma is best made by combining asthma symptom control and exacerbation risk as the principle means by which to determine treatment needs. Incontrovertible evidence and guidelines support treatment initiation with anti-inflammatory medication, completely avoiding reliever-only treatment of mild asthma. Shared decision making with patients and a treatable traits approach will ensure that a holistic approach is taken to maximize patient outcomes. Most importantly, mild asthma should be regarded as a reversible, potentially curable condition, remaining in long-term remission through minimizing triggers and optimizing care.

On-Demand ICS + FABA Combinations in 6-11-Year-Old Children.

In recent years, some new concepts have been added to asthma treatment such as "anti-inflammatory reliever" (ß2-agonist use associated to an inhaled corticosteroid (ICS) as a reliever treatment) that combines the benefits of both therapies and provides short- and long-term benefits for treatment in asthma patients. Robust evidence has been presented in patients over 12 years, and the main changes in the international guidelines for asthma treatment were originally made in this age group. However, a few suggestions have been added to treatments in younger patients, in part because of the scarce evidence that exists in this group. We aim to analyze the information regarding the utilization of ICS + fast-acting beta-agonist (FABA) combination in children between 6 and 11 years. Although up until today only three published trials exist (two studies use beclomethasone + albuterol and one study uses budesonide + formoterol), they provide significant information on the benefits of ICS + FABA use in this population.

The Rubik's Cube of Manufacturers' Coupons: Making the Case for Sneetches.

Description Asthma maintenance inhalers are inordinately expensive, inhibiting patients from affording their medication and compromising compliance and adherence and optimal health outcomes. The objective of this article was to examine and highlight the competitive world and challenged opportunity of manufacturers' coupons discounting the inordinate cost of respiratory inhalers and asthma treatment. The cost of asthma treatment, in particular the cost of respiratory medicines, even with health insurance, can be prohibitive (upwards of $700 per month for one inhaler). Medication costs restrict medication access. Compliance and adherence suffer attested by monthly maintenance inhalers being filled less than 50% of the time. Pharmaceutical manufacturers of branded drugs competitively offer and market discount programs designed to help offset out-of-pocket medication (copay or coinsurance) costs. However, these programs vary depending on the manufacturer and are contingent on the parameters of individual insurance plans and their respective pharmacy benefit managers (PBMs). In an attempt to gain market advantage, manufacturers, coupons frequently change criteria making the opportunity of savings for patients and prescribing clinicians difficult to discern, implement and sustain.

Characteristics of Asthma Exacerbations in Emergency Care in Switzerland-Demographics, Treatment, and Burden of Disease in Patients with Asthma Exacerbations Presenting to an Emergency Department in Switzerland (CARE-S).

Emergency care for asthma is provided by general practitioners, pulmonologists, and emergency departments (EDs). Although it is known that patients presenting to EDs with acute asthma exacerbations are a vulnerable population and that this mode of presentation is a risk marker for more severe complications, research on this population is scarce. We conducted a retrospective study on patients with asthma exacerbations who presented to the ED of the University Hospital Basel, Switzerland, during 2017-2020. Of the last 200 presentations, 100 were selected and analyzed to assess demographic information, the use of previous and ED-prescribed asthma medication, and clinical outcomes after a mean period of time of 18 months. Of these 100 asthma patients, 96 were self-presenters, and 43 had the second highest degree of acuity (emergency severity index 2). Global Initiative for Asthma (GINA) step 1 and step 3 were the most common among patients with known GINA levels, accounting for 22 and 18 patients, respectively. A total of 4 patients were undergoing treatment with oral corticosteroids at presentation, and 34 were at discharge. At presentation, 38 patients used the combination therapy of inhaled corticosteroid/long-acting ß2-agonist (ICS/LABA), and 6 patients underwent ICS monotherapy. At discharge, 68 patients were prescribed with ICS/LABA. At entry to the ED, about one-third of patients did not use any asthma medication. In total, 10 patients were hospitalized. None of them needed invasive or non-invasive ventilation. A follow-up for the study was precluded by the majority of patients. This group of asthma patients seemed particularly vulnerable as their asthma medication at presentation was often not according to guidelines or even lacking, and almost all the patients had self-presented to the ED without any reference from a physician. The majority of patients did not give consent to the collection of any follow-up information. These medical shortcomings reflect an urgent medical need to improve care for patients at high risk of asthma exacerbations.

Co-Developing Patient-Centered Information: A Focus Group Study of Asthma Patients' Preferences and Attitudes towards New Medical Treatment Guidelines.

Studies have suggested patient involvement as an important factor when seeking to improve patient-centered information. The objective of this study was to explore asthma patients' preferences regarding information when co-developing patient-centered information and how they evaluate the material as a supportive initiative when they are deciding whether to switch to the new MART approach. The study was performed as a case study involving qualitative semi-structured focus group interviews inspired by the theoretical framework for supporting patient involvement in research. Two focus group interviews were held, with a total of nine interviewees. Three main interview themes were found: the identification of important topics about the new MART approach, feedback on the design and the preferred implementation of written patient-centered information. The asthma patients preferred written patient-centered material to be short and to be presented briefly at the local community pharmacy, and then discussed more thoroughly with their general practitioner (GP) at a consultation. In conclusion, this study identified asthma patients' preferences when co-developing written patient-centered information and how the patients favored the material to be implemented as a support to them in their decision on whether to change asthma treatment.

Classifying asthma control using salivary and fecal bacterial microbiome in children with moderate-to-severe asthma.

BACKGROUND: Uncontrolled asthma can lead to severe exacerbations and reduced quality of life. Research has shown that the microbiome may be linked with asthma characteristics; however, its association with asthma control has not been explored. We aimed to investigate whether the gastrointestinal microbiome can be used to discriminate between uncontrolled and controlled asthma in children. METHODS: 143 and 103 feces samples were obtained from 143 children with moderate-to-severe asthma aged 6 to 17 years from the SysPharmPediA study. Patients were classified as controlled or uncontrolled asthmatics, and their microbiome at species level was compared using global (alpha/beta) diversity, conventional differential abundance analysis (DAA, analysis of compositions of microbiomes with bias correction), and machine learning [Recursive Ensemble Feature Selection (REFS)]. RESULTS: Global diversity and DAA did not find significant differences between controlled and uncontrolled pediatric asthmatics. REFS detected a set of taxa, including Haemophilus and Veillonella, differentiating uncontrolled and controlled asthma with an average classification accuracy of 81% (saliva) and 86% (feces). These taxa showed enrichment in taxa previously associated with inflammatory diseases for both sampling compartments, and with COPD for the saliva samples. CONCLUSION: Controlled and uncontrolled children with asthma can be differentiated based on their gastrointestinal microbiome using machine learning, specifically REFS. Our results show an association between asthma control and the gastrointestinal microbiome. This suggests that the gastrointestinal microbiome may be a potential biomarker for treatment responsiveness and thereby help to improve asthma control in children.

The role of modeling studies in asthma management and clinical decision-making: a Delphi survey of physician knowledge and perceptions.

OBJECTIVE: To investigate the knowledge and perceptions of physicians on the role of modeling studies in asthma, using a modified Delphi procedure. METHODS: Group opinions among a panel of respiratory experts were obtained using two online questionnaires and a virtual scientific workshop. A consensus was pre-defined as agreement by >75% of participants. RESULTS: From 26 experts who agreed to participate, 22 completed both surveys. At the end of the process, the panel rated their own understanding of modeling as good (77%) but that among physicians in general as poor (77%). Participants agreed that data from modeling studies should be used, at least sometimes, to inform treatment guidelines (91%) and could be useful for guiding clinical decisions (100%). Perceived barriers to using modeling studies were 'A lack of understanding' (81%) and 'A lack of standardized methodology' (82%). Based on data from two modeling studies, no consensus was reached on physicians recommending regular inhaled corticosteroids (ICS) versus as-needed therapy for patients with mild asthma, whereas 77% agreed that they would recommend regular ICS over maintenance and reliever therapy for ≥80% of their patients with moderate asthma. No consensus was reached on the value of modeling data in relation to empirical data. CONCLUSION: There is overall support among respiratory experts for the usefulness of modeling data to guide asthma treatment guidelines and clinical decision making. More publications on modeling data using robust models and accessible terminology will aid the understanding of physicians in general and help clarify the evidence-based value of modeling studies.

A Shift in Asthma Treatment According to New Guidelines: An Evaluation of Asthma Patients' Attitudes towards Treatment Change.

The Global Initiative for Asthma (GINA) has presented a shift in pharmacological asthma treatment. The objective of this study was to explore factors influencing a successful switch to a new asthma treatment approach with a focus on asthma patients' attitudes toward treatment change and supportive initiatives. This study was performed as a case study involving a quantitative questionnaire and a qualitative semi-structured interview. A total of 284 responses were collected from the questionnaire, and 141 responses were included. The results showed that asthma patients thought that effectiveness of the new treatment approach, doctor recommendation, and knowledge of the new treatment approach were the most important factors influencing treatment change considerations. Nine interviews were conducted where the main themes were barriers to a shift in asthma treatment, such as effects and side effects of the new treatment, the role of the general practitioner (GP) and conflicts in agreeing on a treatment plan; as well as facilitators to a shift in asthma treatment, such as trust in the GP and easier inhaler use. We found several supportive initiatives, such as consultation with the GP, handing out information leaflets and a consultation at the pharmacy. In conclusion, this study uniquely identified factors that may influence successful treatment shifts in asthma patients that may be instrumental in understanding similar situations in other pharmacological settings.

Anti ige na asma grave 'relato de caso' / Anti ige in severe asthma 'case report / Anti ige en el asma grave 'informe de un caso

A asma grave é uma doença respiratória crônica que afeta as vias aéreas, provocando inflamação e estreitamento dos brônquios. Esse estreitamento pode dificultar a respiração e causar sintomas como tosse, falta de ar, chiado no peito e aperto no peito. Quando a asma não é controlada adequadamente com medicamentos e outras medidas, ela pode evoluir para um quadro de asma grave. O presente artigo científico consiste em uma revisão literária sobre o tratamento da asma grave com elevados níveis de anticorpos IgE por meio do uso do anticorpo monoclonal Omalizumabe, além de apresentar o relato de caso observacional em um paciente pediátrico atendido em um consultório especializado da cidade de Mineiros no estado de Goiás. Os estudos revisados demonstraram que a terapia com Omalizumabe pode melhorar a função pulmonar, reduzir a necessidade de medicação de resgate e melhorar a qualidade de vida em pacientes com asma grave. No entanto, também foi observado que o benefício do Omalizumabe é mais pronunciado em pacientes com níveis mais elevados de IgE e em pacientes que apresentam sintomas asmáticos frequentes. A revisão literária apresentou evidências consistentes de que o Omalizumabe é uma opção terapêutica eficaz e segura para o tratamento de asma grave com elevados níveis de IgE em pacientes pediátricos. Por fim com objetivo de fornecer informações importantes para médicos e profissionais de saúde sobre o uso do Omalizumabe no tratamento da asma grave em crianças, além de destacar a necessidade de mais pesquisas para avaliar a eficácia e segurança do medicamento em populações maiores e com seguimento mais prolongado.

Severe asthma is a chronic respiratory disease that affects the airways, causing inflammation and narrowing of the bronchi. This narrowing can make breathing difficult and cause symptoms such as coughing, shortness of breath, wheezing, and chest tightness. When asthma is not properly controlled with medication and other measures, it can develop into severe asthma. The present scientific article consists of a literature review on the treatment of severe asthma with high IgE antibody levels by the use of the monoclonal antibody Omalizumab, besides presenting the report of an observational case in a pediatric patient seen at a specialized clinic in the city of Mineiros in the state of Goiás. The studies reviewed showed that Omalizumab therapy can improve lung function, reduce the need for rescue medication, and improve quality of life in patients with severe asthma. However, it was also noted that the benefit of Omalizumab is more pronounced in patients with higher IgE levels and in patients who have frequent asthmatic symptoms. The literature review presented consistent evidence that Omalizumab is an effective and safe therapeutic option for the treatment of severe asthma with high IgE levels in pediatric patients. Finally with aim to provide important information for physicians and health care professionals about the use of Omalizumab in the treatment of severe asthma in children, and to highlight the need for further research to evaluate the efficacy and safety of the drug in larger populations and with longer follow-up.

El asma grave es una enfermedad respiratoria crónica que afecta a las vías respiratorias, causando inflamación y estrechamiento de los bronquios. Este estrechamiento puede dificultar la respiración y causar síntomas como tos, falta de aire, sibilancias y opresión torácica. Cuando el asma no se controla adecuadamente con medicación y otras medidas, puede convertirse en asma grave. El presente artículo científico consiste en una revisión bibliográfica sobre el tratamiento del asma grave con niveles elevados de anticuerpos IgE mediante el uso del anticuerpo monoclonal Omalizumab, además de presentar el informe de un caso observacional en un paciente pediátrico atendido en una clínica especializada de la ciudad de Mineiros, en el estado de Goiás. Los estudios revisados demostraron que el tratamiento con omalizumab puede mejorar la función pulmonar, reducir la necesidad de medicación de rescate y mejorar la calidad de vida en pacientes con asma grave. Sin embargo, también se observó que el beneficio del omalizumab es más pronunciado en pacientes con niveles más altos de IgE y en pacientes que presentan síntomas asmáticos frecuentes. La revisión bibliográfica presentó pruebas consistentes de que omalizumab es una opción terapéutica eficaz y segura para el tratamiento del asma grave con niveles elevados de IgE en pacientes pediátricos. Finalmente con el objetivo de proporcionar información importante para los médicos y profesionales de la salud sobre el uso de Omalizumab en el tratamiento del asma grave en niños, así como destacar la necesidad de nuevas investigaciones para evaluar la eficacia y seguridad del fármaco en poblaciones más grandes y con un seguimiento más prolongado.

Salbutamol in the Management of Asthma: A Review.

Asthma is a common inflammatory disease of the lungs. The prevalence of asthma is increasing worldwide, and the tendency indicates that the number of asthma sufferers will soar in the coming years for several reasons, in particular, the lifestyles we have adopted that expose us to risk factors. Salbutamol is the first selective short-acting ß2-agonist (SABA) used as an alternative reliever in the treatment of asthma. Its therapeutic effect is based on its potent smooth muscle relaxant properties, which allow the inhibition of bronchial smooth muscle contraction and subsequent bronchodilation. Salbutamol can be administered orally, intravenously (IV), intramuscularly (IM), subcutaneously, or by inhalation. For this reason, the pharmacokinetic (PK) parameters-absorption, distribution, metabolism, and elimination-are highly diverse and, consequently, the efficacy and adverse effects also differ between each formulation. Here, we review the pharmacological profile of different salbutamol formulations, focusing on their efficacy and adverse effects for its original application, asthma.

Resveratrol in the treatment of asthma based on an animal model.

Resveratrol is a natural polyphenol found, for example, in red wine, grapes or nuts. One of the resveratrol's health properties is a cardioprotective activity - it is believed that resveratrol is responsible for the French paradox and anticancer activity. Moreover, the effectiveness of resveratrol in the treatment of asthma is confirmed by multiple research. Resveratrol displays a multiway impact on the reduction of the symptoms of the disease which contributes to the alleviation of inflammation i.a. by: inhibition of cellular infiltration, suppression of oxidative stress, reduction in the volume of mucus, relaxation of smooth muscle, stalling of the fibrosis affecting the respiratory tract or counteracting bronchial hyperresponsiveness. Resveratrol reduces the concentration of eosinophils, pro-inflammatory interleukins and interferes with many signal transduction pathways. In case of concomitance of obesity, resveratrol alleviates the course of asthma. The review juxtaposes the mechanisms of resveratrol activity and presents the results of the published research conducted on rodents.

Behavioural side effects of inhaled corticosteroids among children and adolescents with asthma.

BACKGROUND: Inhalation corticosteroids (ICS) are prescribed for treatment of asthma in approximately 3% of all children in Denmark. Despite limited evidence, case reports suggest that ICS-related behavioural adverse drug events (ADEs) may be frequent. In general, underreporting of ADEs to official databases is common, and little is known about doctor's clinical experiences with behavioural ADEs when prescribing ICS for children with asthma. The objective was to investigate the extent of behavioural ADEs in children with asthma treated with ICS by comparing database findings to experiences of specialist doctors. METHODS: First, databases of the European Medicines Agency (EMA) and the Danish Medicines Agency (DKMA) were searched for reports made by healthcare professionals about behavioural ADEs in children from 2009 to 2018. Second, questionnaire data on behavioural ADEs were collected from eight of the 11 specialist doctors responsible for treating children with asthma at the six paediatric departments in Central Denmark Region and North Denmark Region. RESULTS: EMA and DKMA had registered 104 and 3 reports, respectively, on behavioural ADEs during the 10-year study period. In contrast, five of the eight specialist doctors (45.5%) had experienced patients who had developed behavioural changes during ICS treatment. However, none of the five specialist doctors had filed reports on these events to DKMA. CONCLUSION: Behaviour-related ADEs to ICS in children with asthma are likely to be highly underreported in official databases and doctors treating children with ICS should be aware of potential ADEs and consider submitting ADE reports whenever appropriate.

Identification of potential biomarkers and immune infiltration characteristics in severe asthma.

OBJECTIVES: We hope to identify key molecules that can be used as markers of asthma severity and investigate their correlation with immune cell infiltration in severe asthma. METHODS: An asthma dataset was downloaded from the Gene Expression Omnibus database and then processed by R software to obtain differentially expressed genes (DEGs). First, multiple enrichment platforms were applied to analyze crucial biological processes and pathways and protein-protein interaction networks related to the DEGs. We next combined least absolute shrinkage and selection operator logistic regression and the support vector machine-recursive feature elimination algorithms to screen diagnostic markers of severe asthma. Then, a local cohort consisting of 40 asthmatic subjects (24 with moderate asthma and 16 with severe asthma) was used for biomarker validation. Finally, infiltration of immune cells in asthma bronchoalveolar lavage fluid and their correlation with the screened markers was evaluated by CIBERSORT. RESULTS: A total of 97 DEGs were identified in this study. Most of these genes are enriched in T cell activation and immune response in the asthma biological process. CC-chemokine receptor 7 (CCR7) and natural killer cell protein 7(NKG7) were identified as markers of severe asthma. The highest area under the ROC curve (AUC) was from a new indicator combining CCR7 and NKG7 (AUC = 0.851, adj. p < 0.05). Resting and activated memory CD4 T cells, activated NK cells, and CD8 T cells were found to be significantly higher in the severe asthma group (adj. p < 0.01). CCR7 and NKG7 were significantly correlated with these infiltrated cells that showed differences between the two groups. In addition, CCR7 was found to be significantly positively correlated with eosinophils (r = 0.38, adj. p < 0.05) infiltrated in bronchoalveolar lavage fluid. CONCLUSION: CCR7 and NKG7 might be used as potential markers for asthma severity, and their expression may be associated with differences in immune cell infiltration in the moderate and severe asthma groups.

Adherence and quality of life assessment in patients with asthma treatment with budesonide/formoterol via the Elpenhaler device: the COMPLETE study.

BACKGROUND: Asthma is a chronic inflammatory disease of the airways that causes recurring episodes of wheezing, breathlessness, chest tightness and coughing. Inhaled drugs on a daily basis are the cornerstone of asthma treatment, therefore, patient adherence is very important. METHODS: We performed a multicenter, open, non-interventional, observational, prospective study of 716 adult patients diagnosed with asthma receiving FDC (Fixed-dose combination) budesonide/formoterol via the Elpenhaler device. We assessed the adherence to treatment at 3 and 6 months (based on the MMAS-8: 8-item Morisky Medication Adherence Scale), the quality of life and change in forced expiratory volume in 1 s (FEV1) from baseline to follow-up. RESULTS: Approximately 80% of the patients showed medium to high adherence throughout the study. The mean (SD) MMAS-8 score at 6 months was 6.85 (1.54) and we observed a statistically significant shift of patients from the low adherence group to the high adherence group at 6 months. Moreover, after 6 months of treatment with FDC budesonide/formoterol, we observed an increase in the patients' quality of life that as expressed by a change 2.01 (95%CI 1.93-2.10) units in Mini AQLQ (p < 0.0001) that was more pronounced in the high adherence group. The same trend was also observed in terms of spirometry (mean FEV1 2.58 L (0.85) at the end of the study, increased by 220 mL from baseline) with a higher improvement in the medium and high adherence groups. CONCLUSIONS: Treatment with FDC of budesonide/formoterol via the Elpenhaler device was associated with improvement in asthma-related quality of life and lung function over 6 months that were more prominent in patients with higher adherence. TRIAL REGISTRATION: 2017-HAL-EL-74 (ClinicalTrials.gov Identifier: NCT03300076).

Uncontrolled asthma predicts severe COVID-19: a report from the Swedish National Airway Register.

BACKGROUND: Severe asthma increases the risk of severe COVID-19 outcomes such as hospitalization and death. However, more studies are needed to understand the association between asthma and severe COVID-19. METHODS: A cohort of 150,430 adult asthma patients were identified in the Swedish National Airway Register (SNAR) from 2013 to December 2020. Data on body mass index, smoking habits, lung function, and asthma control test (ACT) were obtained from SNAR, and uncontrolled asthma was defined as ACT ⩽19. Patients with severe COVID-19 were identified following hospitalization or in death certificates based on ICD-10 codes U07.1 and U07.2. The Swedish Prescribed Drug register was used to identify comorbidities and data from Statistics Sweden for educational level. Multivariate logistic regression analyses were used to estimate associations with severe COVID-19. RESULTS: Severe COVID-19 was identified in 1067 patients (0.7%). Older age (OR = 1.04, 95% CI = 1.03-1.04), male sex (1.42, 1.25-1.61), overweight (1.56, 1.27-1.91), obesity (2.12, 1.73-2.60), high-dose inhaled corticosteroids in combination with long-acting ß-agonists (1.40, 1.22-1.60), dispensed oral corticosteroids ⩾2 (1.48, 1.25-1.75), uncontrolled asthma (1.64, 1.35-2.00), cardiovascular disease (1.20, 1.03-1.40), depression (1.47, 1.28-1.68), and diabetes (1.52, 1.29-1.78) were associated with severe COVID-19, while current smoking was inversely associated (0.63, 0.47-0.85). When comparing patients who died from COVID-19 with those discharged alive from hospital until 31 December 2020, older age, male sex, and current smoking were associated with COVID-19 death. CONCLUSION: Patients with uncontrolled asthma and high disease burden, including increased asthma medication intensity, should be identified as risk patients for severe COVID-19. Furthermore, current smoking is strongly associated with COVID-19 death in asthma.

miR-144-3p Is a Biomarker Related to Severe Corticosteroid-Dependent Asthma.

MicroRNAs are non-coding molecules that act both as regulators of the epigenetic landscape and as biomarkers for diseases, including asthma. In the era of personalized medicine, there is a need for novel disease-associated biomarkers that can help in classifying diseases into phenotypes for treatment selection. Currently, severe eosinophilic asthma is one of the most widely studied phenotypes in clinical practice, as many patients require higher and higher doses of corticosteroids, which in some cases fail to achieve the desired outcome. Such patients may only benefit from alternative drugs such as biologics, for which novel biomarkers are necessary. The objective of the study was to study the expression of miR-144-3p in order to discover its possible use as a diagnostic biomarker for severe asthma. For this purpose, miR-144-3p was evaluated in airway biopsies and serum from asthmatics and healthy individuals. mRNA was studied in asthmatic biopsies and smooth muscle cells transfected with miR-144-3p mimic. An in silico regulation of miR-144-3p was performed using miRSystem, miRDB, STRING, and ShinyGO for pathway analysis. From our experimental procedures, we found that miR-144-3p is a biomarker associated with asthma severity and corticosteroid treatment. MiR-144-3p is increased in asthmatic lungs, and its presence correlates directly with blood eosinophilia and with the expression of genes involved in asthma pathophysiology in the airways. When studied in serum, this miRNA was increased in severe asthmatics and associated with higher doses of corticosteroids, thereby making it a potential biomarker for severe asthma previously treated with higher doses of corticosteroids. Thus, we can conclude that miR-144-3p is associated with severe diseases in both the airways and serum of asthmatics, and this association is related to corticosteroid treatment.