Anti-IL-5 and anti-IL-5 receptor therapy significantly improves quality of life and FEV1 values in patients with severe asthma

Anti-IL-5 and anti-IL-5 receptor therapy significantly improves quality of life and FEV1 values in patients with severe asthma | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Anti-IL-5 and anti-IL-5 receptor therapy significantly improves quality of life and FEV1 values in patients with severe asthma Anaiza Odalis Villalobos-Alfaro, Haydee Carolina Gutiérrez-Vargas, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6543940/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 13 Aug, 2025 Read the published version in Allergy, Asthma & Clinical Immunology → Version 1 posted 9 You are reading this latest preprint version Abstract Asthma is a chronic inflammatory disease of the airways triggered by exogenous antigens. Among its variants, it is crucial to differentiate between severe asthma and asthma, which is difficult to control. Severe asthma is characterized by a lack of response to high doses of inhaled corticosteroids and long-acting beta-2 agonists, whereas difficult-to-control asthma is associated with poor adherence to treatment, inappropriate use of inhalers, or the presence of uncontrolled comorbidities. In recent years, the use of monoclonal antibodies directed against interleukin-5 (anti-IL-5) and its receptor alpha (anti-IL-5R) has proven to be an effective therapeutic option for patients with severe asthma by reducing the number of eosinophils, which may promote disease remission. This study aimed to evaluate clinical improvement and remission in patients with severe asthma treated with anti-IL-5 and anti-IL-5R antibodies over a period of 12 months. A cohort study was conducted with 49 patients who were diagnosed with severe eosinophilic asthma and who did not respond to conventional treatment. During follow-up, medical control was carried out every 3 months via spirometry, eosinophil counts, quality of life scales and disease control. The results revealed an improvement in FEV1 from 3 months of treatment, with statistical significance at 12 months in patients treated with anti-IL-5 and at 9 months in those treated with anti-IL-5R. In addition, better perceptions of asthma control and quality of life were observed, with significant differences at 6 and 12 months. The correlations between spirometry and the ACT, ACQ and AQLQ reflect a progressive recovery of well-being and function. Finally, the remission rate was 41.1% with anti-IL-5 therapy and 47.3% with anti-IL-5R therapy after one year of follow-up. These findings support the efficacy of treatment with anti-IL-5 and anti-IL-5R in improving severe asthma control and patients' quality of life, suggesting their key role in disease remission. Asthma Anti-IL-5 Anti-IL5R ACQ5 Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 1. Introduction Asthma is a heterogeneous disease characterized by chronic inflammation of the airways caused by exogenous antigens. Different immunological mechanisms are altered in this illness, such as the balance between Th1 and Th2 lymphocytes, leading to an inadequate response to infections and IgE-mediated inflammation of the airways ( 1 ). During the early phase of inflammation, antigen-presenting cells present antigens to Th2 lymphocytes, which produce interleukins, including IL-4, IL-5, and IL-13 ( 1 ). B lymphocytes secrete IgE, which binds to the receptors of mast cells, eosinophils and basophils, sensitizing patients toallergens. Finally, the allergen binds to the IgE present in effector cells, releasing mediators such as histamine, prostaglandins, leukotrienes, etc., contributing to inflammation and classic asthma symptomatology ( 1 ). Many clinical phenotypes of asthma have been identified, some of which are as follows: (I) allergic asthma, (II) nonallergic asthma, (III) cough-variant asthma, cough-predominant asthma, (IV) adult-onset asthma, (V) asthma with persistent airflow limitation, and (VI) asthma with obesity ( 1 ). Severe asthma is defined as asthma that remains uncontrolled despite optimized treatment with high doses of inhaled corticosteroids and long-acting beta-2 agonists (ICS-LABAs); asthma is a common disorder affecting approximately 7.8% of the U.S. population or 23 million Americans ( 2 ). Approximately 10% of adults and 2.5% of children with asthma develop severe asthma, which negatively impacts their quality of life and increases the risk of airflow limitation, exacerbation, hospitalization, and even death ( 3 ). Additionally, this pathology encompasses various clinical phenotypes varying by age of onset, presence of allergies, and coexisting conditions ( 2 , 3 ). These phenotypes include type 2 (T2) and non-T2 asthma, with significant differences in treatment response, particularly to inhaled corticosteroids (ICSs) ( 1 ). T2 asthma primarily features eosinophilic airway inflammation in 50% of cases associated with increased blood eosinophil counts or elevated fractions of exhaled nitric oxide (FeNO), whereas non-T2 asthma includes neutrophilic and pancigranulocytic asthma ( 3 – 7 ). On the other hand, difficult-to-treat asthma is defined as uncontrolled asthma despite adequate treatment. A number of factors, such as poor adherence to treatment or the misuse of inhalers, may lead to treatment failure and to an uncontrolled patient ( 1 ). It is important to distinguish between severe asthma and difficult-to-control asthma, which is caused by modifiable factors such as poor inhalation technique, poor treatment adherence, or the presence of comorbidities such as chronic rhinosinusitis or obesity ( 3 ). To differentiate between uncontrolled and controlled asthma, tools such as the Asthma Control Questionnaire (ACQ5) and Asthma Control Test (ACT) are used in adolescents and adults to assess asthma control and classify patients into different levels on the basis of the reported symptoms ( 41 ). There are different treatments for severe asthma patients. Recently, monoclonal antibodies such as anti-interleukin-5 (Anti-IL-5) and anti-interleukin-5 receptor alpha (Anti-IL5R) have been used to control patients with severe asthma ( 3 ). However, few studies have focused on patients treated with these therapies in real-life settings, especially regarding clinical remission and complete remission, which may involve discontinuation of the therapy. Notably, both antibodies reduce the number of eosinophils, while the anti-IL-5R antibody also depletes basophils ( 3 ). This study aims to compare current epidemiological and follow-up data on biomarkers, respiratory function tests, quality of life scales, and annual remission in patients with severe eosinophilic asthma treated with anti-IL-5 or anti-IL-5R. 2. Materials and methods This cohort study was conducted at ISSSTE Aguascalientes General Hospital, Valentín Gómez Farías Zapopan Hospital, and the Mexican Institute of Social Security Tepic Hospital between February 2021 and February 2023. The study included patients aged 18 to 99 years with confirmed severe eosinophilic asthma type 2, regardless of sex, who did not respond to conventional treatment with high-dose corticosteroids. Those who did not meet the definition of severe asthma, experienced an exacerbation at baseline, were pregnant, or had conditions that could mask asthma control symptoms, such as ischemic heart disease, neurodegenerative diseases, or concomitant cardiorespiratory conditions, were excluded. The study was approved by the ethics committee (Approval No. 2024-RCEI-9), and all participants provided informed consent. Patients who met the definition of severe eosinophilic asthma characterized by uncontrolled asthma despite adequate adherence to inhaled therapy, high-dose ICS/LABA, and controlled modifiable risk factors were included ( 1 ). In addition, patients received at least one year of treatment with anti-IL-5 or anti-IL-5R monoclonal antibodies (benralizumab 30 mg every 4 weeks and then every 8 weeks or mepolizumab 100 mg every 4 weeks) at their respective hospitals. This therapy has been extensively evaluated in controlled clinical trials, establishing that the greatest therapeutic effect is observed with those doses ( 4 – 26 ). During the follow-up period, every three months, medical control, including spirometry tests and eosinophil counts, was performed for each patient. Quality of life (Table 1 ) and asthma control scales (Table 2 ) were applied at each visit to determine the patients’ quality of life, treatment adherence, and biological treatment. (Figs. 1 – 3 ) Table 1 Quality-of-life tools used in this study Test/tool Characteristics Scores/Interpretation Asthma Quality of Life Questionnaire (AQLQ) It is an instrument to assess the quality of life in disease through physical and emotional impact¨. It has 32 items corresponding to 4 dimensions of health: limitations of habitual activities (11 items), symptoms (12 items), emotional function (5 items), and environmental stimuli (4 items) 27 0 = good health-related quality of life 10 = poor health-related quality of life Mini Asthma Quality of Life Questionnaire (mini AQLQ) It consists of 15 questions, grouped into 4 dimensions: symptoms (5 items), activity limitation (4 items), emotional function (3 items) and environmental stimuli (3 items) 28 1 = Lower degree of disability 7 = greater degree of autonomy Saint George's Respiratory Questionnaire (SGRQ- 1) It has 73 items and 3 domains: symptoms, activity, and impact of the disease on daily life. 30 0 = better health status 100 = worse health status The University of California, San Diego Shortness of Breath Questionnaire (UCSD) It is a self-administered questionnaire for dyspnea associated with activities of daily living (ADLs) featuring 24 items. Respondents are asked to rate themselves from 0 ("Not at all") to 5 ("Maximum or unable to do so due to shortness of breath") in two areas: 1. How short of breath they feel when performing various activities (21 items). 2. To what extent shortness of breath, fear of hurting oneself due to overexertion, and fear of shortness of breath limits them in their daily lives (3 items) Scores range from 0 to 120, with higher scores indicating greater dyspnea. The King’s Brief Interstitial Lung Disease (K-BILD) It is a questionnaire on health-related quality of life (HRQoL), a specific measure of interstitial lung disease (ILD), which comprises 15 items. It has three domains: psychological (KBILD-P), dyspnea and activities (KBILD-B), and chest symptoms (KBILD-C)) combined into a total score (KBILD-T) 27 Score ranges from 0 to 100; 100 represents the best state of health. Modified Dyspnea Scale from British Medical Research Council (mMRC) It is used to establish a baseline in respiratory impairment due to dyspnea. It has 5 items (0: absence of dyspnea, 1: dyspnea when walking fast on the flat, 2: dyspnea that limits the pace of other people, 3: dyspnea that causes resting when walking approximately 100 meters, 4: dyspnea that prevents leaving the house) 31 With grades from 0 to 4, where the highest score expresses a greater functional limitation. Hospital Anxiety and Depression Scale (HADS) Instrument for the detection of depressive and anxiety disorders in the framework of hospital or psychiatric services. It is made up of 14 items grouped into two subscales, each with 7 items. Anxiety subscale (psychic manifestations) and depression subscale (focused on anhedonia) 32 In each subscale, the score obtained is interpreted according to the following criteria: * 0–7 normal * 8–10 probable case * 11–21 case of anxiety or depression Table 2 Asthma control tools used in this study. Test/tool Characteristics Scores/Interpretation Asthma Control Test (ACT) It assesses frequency of respiratory distress and general asthma symptoms, use of rescue medications, effect of asthma on daily functioning, and overall self-assessment of asthma control. Scores range from 5 (asthma control) to 25 (complete asthma control). An ACT score > 19 indicates well-controlled asthma. Asthma Control Questionnaire (ACQ) A questionnaire that helps measuring the adequacy of asthma control that occurs spontaneously or because of treatment. The questionnaire consists of 5 questions. 34 Each question is scored from 0 to 6. The points are added up and divided by 5. According to the result: * Less than or equal to 0.75: Adequate asthma control. *0.75 to 1.50: Partially controlled asthma. * Over 1.50: Inadequate asthma control Inhaler adherence test (TAI) Questionnaire aimed at patients with asthma and COPD that allows us to identify patients with low adherence, establish the intensity of adherence (good, intermediate or poor), and provide guidance on the patient's time or pattern of noncompliance. It is made up of 10 questions. 35 The score ranges from 1 (low compliance) to 5 (best compliance) The score provides a total ranging from 10 (minimum) to 50 (maximum) Clinical remission was considered in patients with a sustained absence of asthma symptoms (ACQ 20), no exacerbations in the past year, and optimized lung function with postbronchodilator FEV1 > 80%. Owing to study limitations, complete pathological remission was not evaluated. Statistical analysis. The data obtained in this study were analyzed, and the results were plotted via GraphPad Prism 8.0 software. Descriptive statistics were used to analyze demographic data and remission percentages obtained from patients. Clinical data from the spirometry-FEV1 (percentage as well as the Z-point score), ACT, and ACQ instruments were analyzed via paired RM one-way ANOVA. Quality of life was analyzed via the AQLQ, mini-AQLQ, SGRQ-1, UCSD, K-BILD, and HADSR tests and compared with the paired Friedman test and Dunn’s multiple comparisons. The difference between population data and p values was obtained and plotted in each figure. 3. Results After completing the 12-month timeline defined in this study, which included and compared data from patients who passed through all the diagnostic tests, we established a population of 49 patients (100%) in this study. In total, 76% of the patients were females, and 24% were males; in terms of age, our population had a mean age of 55.78 years (range 21–60. SD: 14.88). An average body mass index of 29.73 was determined (range 20–53). SD 6.1), nasal polyps were found in 20% of the patients, and tobacco was consumed in 29% of the patients. In this study, 17 patients were treated with anti-IL-5 antibodies (35%), and 35 individuals were treated with anti-IL-5 receptor antibodies (65%). The quantification of basal eosinophils before starting the treatment in the anti-IL-5 group revealed a mean of 573.1/1x105 cells/µl (range 180–1,100/1x10 5 cells/µl). SD: 265.2), and for the anti-IL-5R group, the mean number of cells was 839.3/1x105 cells/µl (range: 180–2,668/1x10 5 cells/µl). SD: 547.7). In this study, the following results belong to the two previously mentioned groups. To determine the correlation between spirometry results and the perceived improvement of patients participating in this asthma protocol, we used the asthma control test (ACT) as well as the asthma control questionnaire (ACQ). The ACT results from the anti-IL-5 group showed a similar pattern to those of the spirometry group, demonstrating a significant time-dependent improvement at the end of 12 months in comparison to the first data point at 3 months (Fig. 5 A). Asthma control perception was also enhanced over time in the anti-IL5R group (Fig. 5 B). Furthermore, the ACQ results revealed a reduction in the scores for both groups (Fig. 5 C and D), indicating significant differences only at 12 months. Next, to continue the evaluation of qualityoflife, repercussions after treatment with anti-IL-5 and anti-IL5R antibodies were similar to previously reported data. This study compiled the results of both groups for the six different questionnaires and compared them within the time points set every three months against the baseline data. First, the results from the asthma quality of life questionnaire (AQLQ) (Fig. 6 A) revealed a significant difference at 6 months of treatment. Additionally, these results correlated with the results of the mini-AQLQ instrument used in this work (Fig. 6 B). Afterward, the St. George’s Respiratory Questionnaire (SGRQ) was used to measure the overall wellness perceptions of the patients (Fig. 6 C); interestingly, the patients mentioned an improvement in quality of life with treatment after 3 months. Similar results were observed for the UCSD, K-BILD, and HADSR questionnaires (Fig. 6 D, E, and F), demonstrating a general improvement in different conditions that were reflected in the patients’ perceptions, as well as in their incorporation into normal life. 4. Discussion Severe asthma encompasses various clinical phenotypes that differ on the basis of age of onset, presence of allergies, and other coexisting conditions. These phenotypes include T2 and non-T2 asthma, with significant differences in treatment response, particularly to inhaled corticosteroids (ICSs). T2 asthma is characterized primarily by eosinophilic airway inflammation in 50% of cases and is associated with increased blood eosinophil counts or elevated levels of fractional exhaled nitric oxide (FeNO) ( 3 ). On the other hand, non-T2 asthma includes neutrophilic asthma and paucigranulocytic asthma. It is estimated that up to 83.8% of patients present an eosinophilic phenotype; a Latin American registry reported that 44% of patients had blood eosinophil counts of > 300 cells/mm³ ( 37 ). In this study, 49 patients were evaluated, 76% of whom were women with ages similar to the average age reported previously (55.7 years). Nasal polyposis was observed as a comorbidity in 22% of the patients, which is consistent with previously reported rates (9.8%-35%). However, in our population, active smoking was reported in 29% of cases, which is a higher rate than that reported in previous studies (XALOC 4%, ARABIA 9%, SIROCCO 1%) ( 7 , 17 , 18 , 38 ). This could impact lung function or even exacerbate the condition. In addition, this study reported that 65% of patients used anti-IL-5R therapies, differing from previous real-world studies in which most patients were treated with IL-5 inhibitors. This may explain the higher initial blood eosinophil counts in our study, which reached 2,668 cells/mm³. Previous studies have not demonstrated statistically significant improvements in FEV1. In our study, a significant improvement in FEV1 was observed at 12 months for patients treated with anti-IL-5 and at 9 months for those treated with anti-IL-5R. These findings suggest that respiratory functional effects may occur over the long term. Further studies with longer follow-up periods are necessary to evaluate the effectiveness of pulmonary function, particularly for patients receiving anti-IL-5 therapies. The improvements in disease control, as measured by the ACT and ACQ-6, were similar in both groups (anti-IL-5R and anti-IL-5), which is consistent with the findings of previous studies, which revealed significant improvements at 12 months of treatment compared with early time points ( 7 , 8 , 9 & 14 ). However, the quality of life scales (AQLQ and mini-AQLQ) showed statistically significant improvements as early as 6 months after treatment initiation. he SGRQ-1 questionnaire score decreased during the first 3 months, indicating clinically significant improvements in respiratory symptoms and overall perception of lung function. This positive effect persisted throughout follow-up, although no additional significant differences were observed after the initial months, suggesting that benefits are achieved mainly during the early stages of treatment. This finding is consistent with other studies in which significant correlations were found between changes in SGRQ scores and comparison measures, which is a valid measure of impaired health in diseases of chronic airflow limitation that is repeatable and sensitive ( 43 ). The UCSD questionnaire showed a similar trend, with significant improvements in scores from baseline to 3 and 6 months. While the scores continued to improve, they did not reach statistical significance, possibly indicating a stabilization in the impact of the intervention on daily functioning after the first few months. There is evidence of the use of this scale in interstitial lung disease, where there is evidence of excellent agreement and a moderate positive correlation with the scores of the MRC scale; ( 44 ) however, there is not enough evidence in patients with severe asthma. The K-BILD results revealed statistically significant and sustained improvements across all follow-up points, highlighting the continuous benefits of the intervention on patients’ general well-being and reinforcing its importance in comprehensive condition management. For the HADSR questionnaire, improvements were more modest than those for the other questionnaires. While significant score reductions were observed at 3 and 6 months, these differences were not maintained at 12 months. This suggests that although the intervention initially contributes to improving mental health symptoms, additional strategies may be needed to sustain these effects. Early improvements in quality of life, despite delayed disease control, may be attributed to patients being initially highly symptomatic or being diagnosed late with severe asthma. Therefore, even minimal improvements in disease control could have an early and meaningful impact on quality of life. In our study, clinical remission was achieved in 41.10% of patients treated with anti-IL-5 and in 47.3% of patients treated with anti-IL-5R. This percentage is higher than that reported in previous studies, where the maximum percentage of remission was 43.2% (REMI-M) ( 40 ). Another multicenter observational study reported that 30.12% of patients treated with Anti-IL5 and 40% with Anti-IL5R achieved complete remission after 12 months of treatment ( 42 ). In particular, there was a trend toward higher remission rates with anti-IL-5R, as previously reported ( 7 , 17 , 18 , 38 ), although the difference was not statistically significant. The high remission rate in our study may be due to improved lung function at baseline, fewer exacerbations, and a perception of uncontrolled disease at baseline. Improvements in quality of life occurred before disease control occurred in both groups, and earlier improvements were observed in the anti-IL-5R group. Long-term comparative studies are needed to establish statistically significant differences between the two groups. 5. Conclusions This real-world cohort study demonstrated that biological therapy with anti-IL-5 and anti-IL-5R monoclonal antibodies is effective in improving clinical asthma control, quality of life, and lung function in patients with severe eosinophilic asthma who do not respond to conventional treatment. Both therapies showed significant improvements in ACT, ACQ, and AQLQ scores, with over 40% clinical remission after 12 months of follow-up. Benefits were observed from the early stages of treatment—earlier with anti-IL-5R—and were sustained over time. These findings support the use of targeted therapies as a key tool to modify the clinical course of severe asthma, particularly in settings where optimizing outcomes and resources is essential. Further studies are needed to evaluate the long-term sustainability of these effects and their impact on complete disease remission. Abbreviations The following abbreviations are used in this manuscript: Anti-IL-5 Anti-IL-5R FEV1 ACT TAI ACQ AQLQ mini-AQLQ SGRQ UCSD K-BILD HADS mMRC IL-4 IgE ICS LABA FeNO ANOVA SD REMI-M Anti-interleukin-5 Anti-interleukin-5 receptor alpha Forced expiratory volume Asthma Control Test Inhaler adherence test Asthma Control Questionnaire Asthma Quality of Life Questionnaire Mini Asthma Quality of Life Questionnaire Saint George's Respiratory Questionnaire The University of California, San Diego Shortness of Breath Questionnaire The King’s Brief Interstitial Lung Disease Hospital Anxiety and Depression Scale Modified Dyspnea Scale from British Medical Research Council Interleukin-4 Immunoglobulin E Inhaled corticosteroids Long-acting beta-2 agonists Fraction of exhaled nitric oxide Analysis of variance Standard deviation Maximum percentage of remission Declarations Author Contribution Conceptualization, E.H.; methodology, J.D.; software, J.D.; validation, J.A., D.G., S.P.; formal analysis, H.G., E.,H; research, H.G.; data curation, J.A.; drafting: preparation of the original draft, A.V.; writing: revision and editing, A.V., S.P.; visualization, J.P., A.LL., J.P.,; supervision, S.P.; project management, S.P. 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Enero de 2020 [consultado el 25 de enero de 2025];6(1):00289-2019. Disponible en: https://doi.org/10.1183/23120541.00289-2019 Juniper EF, Guyatt GH, Cox FM, Ferrie PJ, King DR. Development and validation of the Mini Asthma Quality of Life Questionnaire. Eur Respir J [Internet]. Julio de 1999 [consultado el 25 de enero de 2025];14(1):32. Disponible en: https://doi.org/10.1034/j.1399-3003.1999.14a08.x American Thoracic Society | Home [Internet]. The University of California, San Diego Shortness of Breath Questionnaire (SOBQ); [consultado el 25 de enero de 2025]. Disponible en: https://www.thoracic.org/members/assemblies/assemblies/srn/questionaires/sobq.php Gelpi M, Argentiero J, Jones PW, Ronit A. A Scoring Application for the St. George’s Respiratory Questionnaire. Chest [Internet]. Septiembre de 2016 [consultado el 25 de enero de 2025];150(3):747-8. Disponible en: https://doi.org/10.1016/j.chest.2016.05.029 Fabbri LM, Hurd SS. Global Strategy for the Diagnosis, Management and Prevention of COPD: 2003 update. Eur Respir J [Internet]. Julio de 2003 [consultado el 25 de enero de 2025];22(1):1. Disponible en: https://doi.org/10.1183/09031936.03.00063703 Wong AW, Danoff SK. Providing Patient-Centered Care in Interstitial Lung Disease. Clin Chest Med [Internet]. Junio de 2021 [consultado el 25 de enero de 2025];42(2):337-46. Disponible en: https://doi.org/10.1016/j.ccm.2021.03.003 American Thoracic Society | Home [Internet]. Asthma Control Test (ACT); [consultado el 25 de enero de 2025]. Disponible en: https://www.thoracic.org/members/assemblies/assemblies/srn/questionaires/act.php Qoltech - Measurement of Health-Related Quality of Life & Asthma Control [Internet]. Qoltech - Measurement of Health-Related Quality of Life & Asthma Control; [consultado el 25 de enero de 2025]. Disponible en: http://www.qoltech.co.uk/acq.html aria - Web especializada en atención primaria [Internet]. 1aria - TAITEST. Test de adherencia a los inhaladores; abril de 2016 [consultado el 25 de enero de 2025]. Disponible en: https://1aria.com/entrada/taitest-test-de-adherencia-a-los-inhaladores Thomas D, McDonald VM, Pavord ID, Gibson PG. Asthma remission- what is it and how can it be achieved? Eur Respir J [Internet]. 31 de marzo de 2022 [consultado el 25 de enero de 2025]:2102583. Disponible en: https://doi.org/10.1183/13993003.02583-2021 Maspero J, Pavie J, Torres-Duque CA, Montero-Arias F, Cerino-Javier R, Rovira F, Beekman MJ. Toward a better understanding of severe asthma phenotypes in Latin America: results from the PREPARE study. Curr Med Res Opin [Internet]. 5 de febrero de 2023 [consultado el 25 de enero de 2025]:1-35. Disponible en: https://doi.org/10.1080/03007995.2023.2174328 Al-Jahdali H, Wali S, Albanna AS, Allehebi R, Al-Matar H, Fattouh M, Beekman M. Prevalence of eosinophilic, atopic, and overlap phenotypes among patients with severe asthma in Saudi Arabia: a cross-sectional study. BMC Pulm Med [Internet]. 17 de febrero de 2022 [consultado el 25 de enero de 2025];22(1). Disponible en: https://doi.org/10.1186/s12890-022-01856-9 Maglio A, Vitale C, Pelaia C, D’Amato M, Ciampo L, Sferra E, Molino A, Pelaia G, Vatrella A. Severe Asthma Remissions Induced by Biologics Targeting IL5/IL5r: Results from a Multicenter Real-Life Study. Int J Mol Sci [Internet]. 27 de enero de 2023 [consultado el 25 de enero de 2025];24(3):2455. Disponible en: https://doi.org/10.3390/ijms24032455 Crimi C, Nolasco S, Noto A, Maglio A, Quaranta VN, Di Bona D, Scioscia G, Papia F, Caiaffa MF, Calabrese C, D’Amato M, Pelaia C, Campisi R, Vitale C, Ciampo L, Dragonieri S, Minenna E, Massaro F, Gallotti L, Macchia L, Triggiani M, Scichilone N, Valenti G, Pelaia G, Foschino Barbaro MP, Carpagnano GE, Vatrella A, Crimi N, Porto M, Impellizzeri P, Frazzetto V, Bonsignore M, Giannì C, Nardo AA, Vignera F, Busceti MT, Lombardo N, Lacedonia D, Tondo P, Soccio P, Irene Quarato CM, Montagnolo F, Salerno V, Maselli L, Julai E, Coppa F, Grimaldi L, Julai E, Carrieri I, Valeria L. Long-Term Clinical and Sustained REMIssion in Severe Eosinophilic Asthma treated with Mepolizumab: The REMI-M study. J Allergy Clin Immunol [Internet]. Agosto de 2024 [consultado el 25 de enero de 2025]. Disponible en: https://doi.org/10.1016/j.jaip.2024.08.033 Rhee H, Love T, Mammen J. Comparing Asthma Control Questionnaire (ACQ) and National Asthma Education and Prevention Program (NAEPP) asthma control criteria. Ann Allergy Asthma Amp Immunol [Internet]. Enero de 2019 [consultado el 25 de enero de 2025];122(1):58-64. Disponible en: https://doi.org/10.1016/j.anai.2018.09.448 Maglio A, Vitale C, Pelaia C, D’Amato M, Ciampo L, Sferra E, Molino A, Pelaia G, Vatrella A. Severe Asthma Remissions Induced by Biologics Targeting IL5/IL5r: Results from a Multicenter Real-Life Study. Int J Mol Sci [Internet]. 27 de enero de 2023 [consultado el 3 de abril de 2025];24(3):2455. Disponible en: https://doi.org/10.3390/ijms24032455 Jones PW, Quirk FH, Baveystock CM, Littlejohns P. A Self-complete Measure of Health Status for Chronic Airflow Limitation: The St. George's Respiratory Questionnaire. Am Rev Respir Dis [Internet]. Junio de 1992 [consultado el 3 de abril de 2025];145(6):1321-7. Disponible en: https://doi.org/10.1164/ajrccm/145.6.1321 Silva1 H, Cruz Mantoani1 L, Ludovico Zamboti1 C, Florentin Aguiar1 W, L Ries2 A, Ferreira Lima Gonçalves1 A, Garcia da Silva1 T, Ribeiro3 M, Pitta1 F, Augusto Camillo1,4 C. Validation of the Brazilian Portuguese version of the University of California San Diego Shortness of Breath Questionnaire in patients with interstitial lung disease. J Bras Pneumol [Internet]. 31 de diciembre de 2021 [consultado el 3 de abril de 2025]:e20210172. Disponible en: https://doi.org/10.36416/1806-3756/e20210172 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 13 Aug, 2025 Read the published version in Allergy, Asthma & Clinical Immunology → Version 1 posted Editorial decision: Revision requested 16 Jun, 2025 Reviews received at journal 16 Jun, 2025 Reviews received at journal 22 May, 2025 Reviewers agreed at journal 18 May, 2025 Reviewers agreed at journal 13 May, 2025 Reviewers invited by journal 12 May, 2025 Editor assigned by journal 30 Apr, 2025 Submission checks completed at journal 30 Apr, 2025 First submitted to journal 28 Apr, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6543940","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":456071342,"identity":"2b119794-cbd8-4554-9723-380c5a90345f","order_by":0,"name":"Anaiza Odalis Villalobos-Alfaro","email":"","orcid":"","institution":"Cuauhtémoc University","correspondingAuthor":false,"prefix":"","firstName":"Anaiza","middleName":"Odalis","lastName":"Villalobos-Alfaro","suffix":""},{"id":456071343,"identity":"c8b5003f-92bb-4c46-81f2-bffac6d22934","order_by":1,"name":"Haydee Carolina Gutiérrez-Vargas","email":"","orcid":"","institution":"Institute for 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05:08:20","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6543940/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6543940/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s13223-025-00979-y","type":"published","date":"2025-08-13T15:57:46+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":82886982,"identity":"849b2ede-017b-48f4-82d1-1e3a54b85780","added_by":"auto","created_at":"2025-05-16 11:55:06","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":43845,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eClinical asthma patient flowchart used in this study from diagnosis to treatment.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Picture1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6543940/v1/5754b5af754dab58ef38a155.jpg"},{"id":82888602,"identity":"6fa989bc-f695-4766-926c-cdf915ed0136","added_by":"auto","created_at":"2025-05-16 12:03:06","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":56441,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAsthma patients’ outcomes in consideration for this study.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Picture2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6543940/v1/97374f9785072aacf46c6cc2.jpg"},{"id":82886985,"identity":"23d4c17a-8144-421e-8008-f88a97d44e21","added_by":"auto","created_at":"2025-05-16 11:55:06","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":49259,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAlgorithm used to monitor patients in this study for a period of 12 months.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Picture3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6543940/v1/e4a29a025163c8d81087c7a1.jpg"},{"id":82886990,"identity":"0618b582-978a-42f5-a316-ccc687bc8487","added_by":"auto","created_at":"2025-05-16 11:55:07","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":59514,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eLung capacity analysis through the treatment of patients with anti-IL-5 and anti-IL-5R. \u003c/strong\u003eLung capacity was evaluated using FEV1 with spirometry. (A) The percentage of lung capacity in the anti-IL-5 group showed an improvement beginning at 3 months and continuing until the final timepoint of the timeline and being statistically significant at that point. In the anti-IL-5R group (B), this behavior was also observed with significant results after 6 months of treatment. On the other hand, although in the FEV1 expressed by Z-point score, the patients from both groups (C and D) showed a decrease, neither the anti-IL-5 nor anti-IL-5R group appeared statistically significant. Paired RM one-way ANOVA, bars represent the geometric mean, while each data point represents a single patient.\u003c/p\u003e","description":"","filename":"Picture4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6543940/v1/2b47bdb76293145234a17f08.jpg"},{"id":82886992,"identity":"3fd11a7a-59d7-4ec7-861d-394a4736d8ec","added_by":"auto","created_at":"2025-05-16 11:55:07","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":215318,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eControl and improvement perceptions of asthma patients using ACT and ACQ tools. \u003c/strong\u003eThe patient´s perception of improvement using the ACT for the anti-IL-5 group (A) showed a significant improvement after 12 months of treatment. Similar results were observed for the anti-IL-5R group (B). Moreover, the ACQ results revealed significant improvement after 12 months for anti-IL-5 (C) and anti-IL-5R therapies (D). Paired RM one-way ANOV A, bars represent the geometric mean, while each data point represents a single patient.\u003c/p\u003e","description":"","filename":"Picture5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6543940/v1/cb6c8b4f0ad3ebaff1758aa6.jpg"},{"id":82886991,"identity":"4bd82189-b1c8-4f33-a86d-241e54866fc2","added_by":"auto","created_at":"2025-05-16 11:55:07","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":83101,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAssessment of quality of life in asthma patients treated with anti-IL-5 and anti-IL5R antibodies using AQLQ, mini-AQLQ, SGRQ-1, UCSD, K-BILD, and HADSR. \u003c/strong\u003eTo generate a global understanding of the\u003cstrong\u003e \u003c/strong\u003equality-of-life progress by patients over time, this study collected data from six different instruments. There was\u003cstrong\u003e \u003c/strong\u003estatistical significance in all these tools after completing 6 months of treatment. Paired Friedman test, Dunn’s\u003cstrong\u003e \u003c/strong\u003emultiple comparisons\u003c/p\u003e","description":"","filename":"Picture6.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6543940/v1/30c69c776f558bd005c4e985.jpg"},{"id":82887000,"identity":"2951923a-8440-4adc-8b4f-85c3d745e7e7","added_by":"auto","created_at":"2025-05-16 11:55:07","extension":"jpg","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":24382,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eRemission percentage of patients treated after one year with anti-IL-5 or anti-IL5R antibodies. \u003c/strong\u003eThe percentage of patients who reported remission after completing 12 months of treatment with the anti-IL-5 drug (A) and with the anti-IL5R drug (B) was 41.10% and 47.30%, respectively. After comparing the data between both groups, no differences were observed.\u003c/p\u003e","description":"","filename":"Picture7.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6543940/v1/307d3dcf4e394101b6169261.jpg"},{"id":89310668,"identity":"08e9b9da-7881-4788-af8f-e22a90b227b2","added_by":"auto","created_at":"2025-08-18 16:09:29","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1436528,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6543940/v1/cb13996c-b407-42cb-87ee-904c0d609469.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Anti-IL-5 and anti-IL-5 receptor therapy significantly improves quality of life and FEV1 values in patients with severe asthma","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eAsthma is a heterogeneous disease characterized by chronic inflammation of the airways caused by exogenous antigens. Different immunological mechanisms are altered in this illness, such as the balance between Th1 and Th2 lymphocytes, leading to an inadequate response to infections and IgE-mediated inflammation of the airways (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). During the early phase of inflammation, antigen-presenting cells present antigens to Th2 lymphocytes, which produce interleukins, including IL-4, IL-5, and IL-13 (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). B lymphocytes secrete IgE, which binds to the receptors of mast cells, eosinophils and basophils, sensitizing patients toallergens. Finally, the allergen binds to the IgE present in effector cells, releasing mediators such as histamine, prostaglandins, leukotrienes, etc., contributing to inflammation and classic asthma symptomatology (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Many clinical phenotypes of asthma have been identified, some of which are as follows: (I) allergic asthma, (II) nonallergic asthma, (III) cough-variant asthma, cough-predominant asthma, (IV) adult-onset asthma, (V) asthma with persistent airflow limitation, and (VI) asthma with obesity (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eSevere asthma is defined as asthma that remains uncontrolled despite optimized treatment with high doses of inhaled corticosteroids and long-acting beta-2 agonists (ICS-LABAs); asthma is a common disorder affecting approximately 7.8% of the U.S. population or 23\u0026nbsp;million Americans (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Approximately 10% of adults and 2.5% of children with asthma develop severe asthma, which negatively impacts their quality of life and increases the risk of airflow limitation, exacerbation, hospitalization, and even death (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Additionally, this pathology encompasses various clinical phenotypes varying by age of onset, presence of allergies, and coexisting conditions (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). These phenotypes include type 2 (T2) and non-T2 asthma, with significant differences in treatment response, particularly to inhaled corticosteroids (ICSs) (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). T2 asthma primarily features eosinophilic airway inflammation in 50% of cases associated with increased blood eosinophil counts or elevated fractions of exhaled nitric oxide (FeNO), whereas non-T2 asthma includes neutrophilic and pancigranulocytic asthma (\u003cspan additionalcitationids=\"CR4 CR5 CR6\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOn the other hand, difficult-to-treat asthma is defined as uncontrolled asthma despite adequate treatment. A number of factors, such as poor adherence to treatment or the misuse of inhalers, may lead to treatment failure and to an uncontrolled patient (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). It is important to distinguish between severe asthma and difficult-to-control asthma, which is caused by modifiable factors such as poor inhalation technique, poor treatment adherence, or the presence of comorbidities such as chronic rhinosinusitis or obesity (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). To differentiate between uncontrolled and controlled asthma, tools such as the Asthma Control Questionnaire (ACQ5) and Asthma Control Test (ACT) are used in adolescents and adults to assess asthma control and classify patients into different levels on the basis of the reported symptoms (\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThere are different treatments for severe asthma patients. Recently, monoclonal antibodies such as anti-interleukin-5 (Anti-IL-5) and anti-interleukin-5 receptor alpha (Anti-IL5R) have been used to control patients with severe asthma (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). However, few studies have focused on patients treated with these therapies in real-life settings, especially regarding clinical remission and complete remission, which may involve discontinuation of the therapy. Notably, both antibodies reduce the number of eosinophils, while the anti-IL-5R antibody also depletes basophils (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThis study aims to compare current epidemiological and follow-up data on biomarkers, respiratory function tests, quality of life scales, and annual remission in patients with severe eosinophilic asthma treated with anti-IL-5 or anti-IL-5R.\u003c/p\u003e"},{"header":"2. Materials and methods","content":"\u003cp\u003eThis cohort study was conducted at ISSSTE Aguascalientes General Hospital, Valent\u0026iacute;n G\u0026oacute;mez Far\u0026iacute;as Zapopan Hospital, and the Mexican Institute of Social Security Tepic Hospital between February 2021 and February 2023. The study included patients aged 18 to 99 years with confirmed severe eosinophilic asthma type 2, regardless of sex, who did not respond to conventional treatment with high-dose corticosteroids. Those who did not meet the definition of severe asthma, experienced an exacerbation at baseline, were pregnant, or had conditions that could mask asthma control symptoms, such as ischemic heart disease, neurodegenerative diseases, or concomitant cardiorespiratory conditions, were excluded. The study was approved by the ethics committee (Approval No. 2024-RCEI-9), and all participants provided informed consent.\u003c/p\u003e \u003cp\u003ePatients who met the definition of severe eosinophilic asthma characterized by uncontrolled asthma despite adequate adherence to inhaled therapy, high-dose ICS/LABA, and controlled modifiable risk factors were included (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). In addition, patients received at least one year of treatment with anti-IL-5 or anti-IL-5R monoclonal antibodies (benralizumab 30 mg every 4 weeks and then every 8 weeks or mepolizumab 100 mg every 4 weeks) at their respective hospitals. This therapy has been extensively evaluated in controlled clinical trials, establishing that the greatest therapeutic effect is observed with those doses (\u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8 CR9 CR10 CR11 CR12 CR13 CR14 CR15 CR16 CR17 CR18 CR19 CR20 CR21 CR22 CR23 CR24 CR25\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e During the follow-up period, every three months, medical control, including spirometry tests and eosinophil counts, was performed for each patient. Quality of life (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) and asthma control scales (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) were applied at each visit to determine the patients\u0026rsquo; quality of life, treatment adherence, and biological treatment. (Figs.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eQuality-of-life tools used in this study\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTest/tool\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eScores/Interpretation\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAsthma Quality of Life Questionnaire (AQLQ)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIt is an instrument to assess the quality of life in disease through physical and emotional impact\u0026uml;.\u003c/p\u003e \u003cp\u003eIt has 32 items corresponding to 4 dimensions of health: limitations of habitual activities (11 items), symptoms (12 items), emotional function (5 items), and environmental stimuli (4 items)\u003csup\u003e27\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u0026thinsp;=\u0026thinsp;good health-related quality of life\u003c/p\u003e \u003cp\u003e10\u0026thinsp;=\u0026thinsp;poor health-related quality of life\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMini Asthma Quality of Life Questionnaire (mini AQLQ)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIt consists of 15 questions, grouped into 4 dimensions: symptoms (5 items), activity limitation (4 items), emotional function (3 items) and environmental stimuli (3 items) \u003csup\u003e28\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u0026thinsp;=\u0026thinsp;Lower degree of disability\u003c/p\u003e \u003cp\u003e7\u0026thinsp;=\u0026thinsp;greater degree of autonomy\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSaint George's Respiratory Questionnaire (SGRQ- 1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIt has 73 items and 3 domains: symptoms, activity, and impact of the disease on daily life. \u003csup\u003e30\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u0026thinsp;=\u0026thinsp;better health status\u003c/p\u003e \u003cp\u003e100\u0026thinsp;=\u0026thinsp;worse health status\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThe University of California, San Diego Shortness of Breath Questionnaire (UCSD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIt is a self-administered questionnaire for dyspnea associated with activities of daily living (ADLs) featuring 24 items. Respondents are asked to rate themselves from 0 (\"Not at all\") to 5 (\"Maximum or unable to do so due to shortness of breath\") in two areas:\u003c/p\u003e \u003cp\u003e1. \u0026nbsp;How short of breath they feel when performing various activities (21 items).\u003c/p\u003e \u003cp\u003e2.\u0026nbsp;To what extent shortness of breath, fear of hurting oneself due to overexertion, and fear of shortness of breath limits them in their daily lives (3 items)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eScores range from 0 to 120, with higher scores indicating greater dyspnea.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThe King\u0026rsquo;s Brief Interstitial Lung Disease (K-BILD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIt is a questionnaire on health-related quality of life (HRQoL), a specific measure of interstitial lung disease (ILD), which comprises 15 items.\u003c/p\u003e \u003cp\u003eIt has three domains: psychological (KBILD-P), dyspnea and activities (KBILD-B), and chest symptoms (KBILD-C)) combined into a total score (KBILD-T)\u003csup\u003e27\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eScore ranges from 0 to 100; 100 represents the best state of health.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModified Dyspnea Scale from British Medical Research Council (mMRC)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIt is used to establish a baseline in respiratory impairment due to dyspnea.\u003c/p\u003e \u003cp\u003eIt has 5 items (0: absence of dyspnea, 1: dyspnea when walking fast on the flat, 2: dyspnea that limits the pace of other people, 3: dyspnea that causes resting when walking approximately 100 meters, 4: dyspnea that prevents leaving the house) \u003csup\u003e31\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eWith grades from 0 to 4, where the highest score expresses a greater functional limitation.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospital Anxiety and Depression Scale (HADS)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInstrument for the detection of depressive and anxiety disorders in the framework of hospital or psychiatric services.\u003c/p\u003e \u003cp\u003eIt is made up of 14 items grouped into two subscales, each with 7 items. Anxiety subscale (psychic manifestations) and depression subscale (focused on anhedonia)\u003csup\u003e32\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIn each subscale, the score obtained is interpreted according to the following criteria:\u003c/p\u003e \u003cp\u003e* 0\u0026ndash;7 normal\u003c/p\u003e \u003cp\u003e* 8\u0026ndash;10 probable case\u003c/p\u003e \u003cp\u003e* 11\u0026ndash;21 case of anxiety or depression\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAsthma control tools used in this study.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTest/tool\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eScores/Interpretation\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAsthma Control Test (ACT)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIt assesses frequency of respiratory distress and general asthma symptoms, use of rescue medications, effect of asthma on daily functioning, and overall self-assessment of asthma control.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eScores range from 5 (asthma control) to 25 (complete asthma control).\u003c/p\u003e \u003cp\u003eAn ACT score\u0026thinsp;\u0026gt;\u0026thinsp;19 indicates well-controlled asthma.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAsthma Control Questionnaire\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e(ACQ)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA questionnaire that helps measuring the adequacy of asthma control that occurs spontaneously or because of treatment. The questionnaire consists of 5 questions. \u003csup\u003e34\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eEach question is scored from 0 to 6. The points are added up and divided by 5. According to the result:\u003c/p\u003e \u003cp\u003e* Less than or equal to 0.75: Adequate asthma control.\u003c/p\u003e \u003cp\u003e*0.75 to 1.50: Partially controlled asthma.\u003c/p\u003e \u003cp\u003e* Over 1.50: Inadequate asthma control\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eInhaler adherence test\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e(TAI)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eQuestionnaire aimed at patients with asthma and COPD that allows us to identify patients with low adherence, establish the intensity of adherence (good, intermediate or poor), and provide guidance on the patient's time or pattern of noncompliance. It is made up of 10 questions. \u003csup\u003e35\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eThe score ranges from 1 (low compliance) to 5 (best compliance)\u003c/p\u003e \u003cp\u003eThe score provides a total ranging from 10 (minimum) to 50 (maximum)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eClinical remission was considered in patients with a sustained absence of asthma symptoms (ACQ\u0026thinsp;\u0026lt;\u0026thinsp;1 or ACT\u0026thinsp;\u0026gt;\u0026thinsp;20), no exacerbations in the past year, and optimized lung function with postbronchodilator FEV1\u0026thinsp;\u0026gt;\u0026thinsp;80%. Owing to study limitations, complete pathological remission was not evaluated.\u003c/p\u003e \u003cp\u003eStatistical analysis. The data obtained in this study were analyzed, and the results were plotted via GraphPad Prism 8.0 software. Descriptive statistics were used to analyze demographic data and remission percentages obtained from patients. Clinical data from the spirometry-FEV1 (percentage as well as the Z-point score), ACT, and ACQ instruments were analyzed via paired RM one-way ANOVA. Quality of life was analyzed via the AQLQ, mini-AQLQ, SGRQ-1, UCSD, K-BILD, and HADSR tests and compared with the paired Friedman test and Dunn\u0026rsquo;s multiple comparisons. The difference between population data and p values was obtained and plotted in each figure.\u003c/p\u003e"},{"header":"3. Results","content":"\u003cp\u003eAfter completing the 12-month timeline defined in this study, which included and compared data from patients who passed through all the diagnostic tests, we established a population of 49 patients (100%) in this study. In total, 76% of the patients were females, and 24% were males; in terms of age, our population had a mean age of 55.78 years (range 21\u0026ndash;60. SD: 14.88). An average body mass index of 29.73 was determined (range 20\u0026ndash;53). SD 6.1), nasal polyps were found in 20% of the patients, and tobacco was consumed in 29% of the patients. In this study, 17 patients were treated with anti-IL-5 antibodies (35%), and 35 individuals were treated with anti-IL-5 receptor antibodies (65%). The quantification of basal eosinophils before starting the treatment in the anti-IL-5 group revealed a mean of 573.1/1x105 cells/\u0026micro;l (range 180\u0026ndash;1,100/1x10\u003csup\u003e5\u003c/sup\u003e cells/\u0026micro;l). SD: 265.2), and for the anti-IL-5R group, the mean number of cells was 839.3/1x105 cells/\u0026micro;l (range: 180\u0026ndash;2,668/1x10\u003csup\u003e5\u003c/sup\u003e cells/\u0026micro;l). SD: 547.7). In this study, the following results belong to the two previously mentioned groups.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eTo determine the correlation between spirometry results and the perceived improvement of patients participating in this asthma protocol, we used the asthma control test (ACT) as well as the asthma control questionnaire (ACQ). The ACT results from the anti-IL-5 group showed a similar pattern to those of the spirometry group, demonstrating a significant time-dependent improvement at the end of 12 months in comparison to the first data point at 3 months (Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e5\u003c/span\u003eA). Asthma control perception was also enhanced over time in the anti-IL5R group (Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e5\u003c/span\u003eB). Furthermore, the ACQ results revealed a reduction in the scores for both groups (Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e5\u003c/span\u003eC and D), indicating significant differences only at 12 months.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eNext, to continue the evaluation of qualityoflife, repercussions after treatment with anti-IL-5 and anti-IL5R antibodies were similar to previously reported data. This study compiled the results of both groups for the six different questionnaires and compared them within the time points set every three months against the baseline data. First, the results from the asthma quality of life questionnaire (AQLQ) (Fig.\u0026nbsp;\u003cspan refid=\"Fig11\" class=\"InternalRef\"\u003e6\u003c/span\u003eA) revealed a significant difference at 6 months of treatment. Additionally, these results correlated with the results of the mini-AQLQ instrument used in this work (Fig.\u0026nbsp;\u003cspan refid=\"Fig11\" class=\"InternalRef\"\u003e6\u003c/span\u003eB). Afterward, the St. George\u0026rsquo;s Respiratory Questionnaire (SGRQ) was used to measure the overall wellness perceptions of the patients (Fig.\u0026nbsp;\u003cspan refid=\"Fig11\" class=\"InternalRef\"\u003e6\u003c/span\u003eC); interestingly, the patients mentioned an improvement in quality of life with treatment after 3 months. Similar results were observed for the UCSD, K-BILD, and HADSR questionnaires (Fig.\u0026nbsp;\u003cspan refid=\"Fig11\" class=\"InternalRef\"\u003e6\u003c/span\u003eD, E, and F), demonstrating a general improvement in different conditions that were reflected in the patients\u0026rsquo; perceptions, as well as in their incorporation into normal life.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eSevere asthma encompasses various clinical phenotypes that differ on the basis of age of onset, presence of allergies, and other coexisting conditions. These phenotypes include T2 and non-T2 asthma, with significant differences in treatment response, particularly to inhaled corticosteroids (ICSs). T2 asthma is characterized primarily by eosinophilic airway inflammation in 50% of cases and is associated with increased blood eosinophil counts or elevated levels of fractional exhaled nitric oxide (FeNO) (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). On the other hand, non-T2 asthma includes neutrophilic asthma and paucigranulocytic asthma. It is estimated that up to 83.8% of patients present an eosinophilic phenotype; a Latin American registry reported that 44% of patients had blood eosinophil counts of \u0026gt;\u0026thinsp;300 cells/mm\u0026sup3; (\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e). In this study, 49 patients were evaluated, 76% of whom were women with ages similar to the average age reported previously (55.7 years). Nasal polyposis was observed as a comorbidity in 22% of the patients, which is consistent with previously reported rates (9.8%-35%). However, in our population, active smoking was reported in 29% of cases, which is a higher rate than that reported in previous studies (XALOC 4%, ARABIA 9%, SIROCCO 1%) (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e). This could impact lung function or even exacerbate the condition.\u003c/p\u003e \u003cp\u003eIn addition, this study reported that 65% of patients used anti-IL-5R therapies, differing from previous real-world studies in which most patients were treated with IL-5 inhibitors. This may explain the higher initial blood eosinophil counts in our study, which reached 2,668 cells/mm\u0026sup3;. Previous studies have not demonstrated statistically significant improvements in FEV1. In our study, a significant improvement in FEV1 was observed at 12 months for patients treated with anti-IL-5 and at 9 months for those treated with anti-IL-5R. These findings suggest that respiratory functional effects may occur over the long term. Further studies with longer follow-up periods are necessary to evaluate the effectiveness of pulmonary function, particularly for patients receiving anti-IL-5 therapies.\u003c/p\u003e \u003cp\u003eThe improvements in disease control, as measured by the ACT and ACQ-6, were similar in both groups (anti-IL-5R and anti-IL-5), which is consistent with the findings of previous studies, which revealed significant improvements at 12 months of treatment compared with early time points (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e \u0026amp; \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). However, the quality of life scales (AQLQ and mini-AQLQ) showed statistically significant improvements as early as 6 months after treatment initiation. he SGRQ-1 questionnaire score decreased during the first 3 months, indicating clinically significant improvements in respiratory symptoms and overall perception of lung function. This positive effect persisted throughout follow-up, although no additional significant differences were observed after the initial months, suggesting that benefits are achieved mainly during the early stages of treatment. This finding is consistent with other studies in which significant correlations were found between changes in SGRQ scores and comparison measures, which is a valid measure of impaired health in diseases of chronic airflow limitation that is repeatable and sensitive (\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e). The UCSD questionnaire showed a similar trend, with significant improvements in scores from baseline to 3 and 6 months. While the scores continued to improve, they did not reach statistical significance, possibly indicating a stabilization in the impact of the intervention on daily functioning after the first few months. There is evidence of the use of this scale in interstitial lung disease, where there is evidence of excellent agreement and a moderate positive correlation with the scores of the MRC scale; (\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e) however, there is not enough evidence in patients with severe asthma. The K-BILD results revealed statistically significant and sustained improvements across all follow-up points, highlighting the continuous benefits of the intervention on patients\u0026rsquo; general well-being and reinforcing its importance in comprehensive condition management. For the HADSR questionnaire, improvements were more modest than those for the other questionnaires. While significant score reductions were observed at 3 and 6 months, these differences were not maintained at 12 months. This suggests that although the intervention initially contributes to improving mental health symptoms, additional strategies may be needed to sustain these effects.\u003c/p\u003e \u003cp\u003eEarly improvements in quality of life, despite delayed disease control, may be attributed to patients being initially highly symptomatic or being diagnosed late with severe asthma. Therefore, even minimal improvements in disease control could have an early and meaningful impact on quality of life.\u003c/p\u003e \u003cp\u003eIn our study, clinical remission was achieved in 41.10% of patients treated with anti-IL-5 and in 47.3% of patients treated with anti-IL-5R. This percentage is higher than that reported in previous studies, where the maximum percentage of remission was 43.2% (REMI-M) (\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e). Another multicenter observational study reported that 30.12% of patients treated with Anti-IL5 and 40% with Anti-IL5R achieved complete remission after 12 months of treatment (\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e). In particular, there was a trend toward higher remission rates with anti-IL-5R, as previously reported (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e), although the difference was not statistically significant. The high remission rate in our study may be due to improved lung function at baseline, fewer exacerbations, and a perception of uncontrolled disease at baseline.\u003c/p\u003e \u003cp\u003eImprovements in quality of life occurred before disease control occurred in both groups, and earlier improvements were observed in the anti-IL-5R group. Long-term comparative studies are needed to establish statistically significant differences between the two groups.\u003c/p\u003e"},{"header":"5. Conclusions","content":"\u003cp\u003eThis real-world cohort study demonstrated that biological therapy with anti-IL-5 and anti-IL-5R monoclonal antibodies is effective in improving clinical asthma control, quality of life, and lung function in patients with severe eosinophilic asthma who do not respond to conventional treatment. Both therapies showed significant improvements in ACT, ACQ, and AQLQ scores, with over 40% clinical remission after 12 months of follow-up. Benefits were observed from the early stages of treatment\u0026mdash;earlier with anti-IL-5R\u0026mdash;and were sustained over time. These findings support the use of targeted therapies as a key tool to modify the clinical course of severe asthma, particularly in settings where optimizing outcomes and resources is essential. Further studies are needed to evaluate the long-term sustainability of these effects and their impact on complete disease remission.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003ch1\u003eThe following abbreviations are used in this manuscript:\u003c/h1\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"601\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003eAnti-IL-5\u003c/p\u003e\n \u003cp\u003eAnti-IL-5R\u003c/p\u003e\n \u003cp\u003eFEV1\u003c/p\u003e\n \u003cp\u003eACT\u003c/p\u003e\n \u003cp\u003eTAI\u003c/p\u003e\n \u003cp\u003eACQ\u003c/p\u003e\n \u003cp\u003eAQLQ\u003c/p\u003e\n \u003cp\u003emini-AQLQ\u003c/p\u003e\n \u003cp\u003eSGRQ\u003c/p\u003e\n \u003cp\u003eUCSD\u003c/p\u003e\n \u003cp\u003eK-BILD\u003c/p\u003e\n \u003cp\u003eHADS\u003c/p\u003e\n \u003cp\u003emMRC\u003c/p\u003e\n \u003cp\u003eIL-4\u003c/p\u003e\n \u003cp\u003eIgE\u003c/p\u003e\n \u003cp\u003eICS\u003c/p\u003e\n \u003cp\u003eLABA\u003c/p\u003e\n \u003cp\u003eFeNO\u003c/p\u003e\n \u003cp\u003eANOVA\u003c/p\u003e\n \u003cp\u003eSD\u003c/p\u003e\n \u003cp\u003eREMI-M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 499px;\"\u003e\n \u003cp\u003eAnti-interleukin-5\u003c/p\u003e\n \u003cp\u003eAnti-interleukin-5 receptor alpha\u003c/p\u003e\n \u003cp\u003eForced expiratory volume\u003c/p\u003e\n \u003cp\u003eAsthma Control Test\u003c/p\u003e\n \u003cp\u003eInhaler adherence test\u003c/p\u003e\n \u003cp\u003eAsthma Control Questionnaire\u003c/p\u003e\n \u003cp\u003eAsthma Quality of Life Questionnaire\u003c/p\u003e\n \u003cp\u003eMini Asthma Quality of Life Questionnaire\u003c/p\u003e\n \u003cp\u003eSaint George\u0026apos;s Respiratory Questionnaire\u003c/p\u003e\n \u003cp\u003eThe University of California, San Diego Shortness of Breath Questionnaire\u003c/p\u003e\n \u003cp\u003eThe King\u0026rsquo;s Brief Interstitial Lung Disease\u003c/p\u003e\n \u003cp\u003eHospital Anxiety and Depression Scale\u003c/p\u003e\n \u003cp\u003eModified Dyspnea Scale from British Medical Research Council\u003c/p\u003e\n \u003cp\u003eInterleukin-4\u003c/p\u003e\n \u003cp\u003eImmunoglobulin E\u003c/p\u003e\n \u003cp\u003eInhaled corticosteroids\u003c/p\u003e\n \u003cp\u003eLong-acting beta-2 agonists\u003c/p\u003e\n \u003cp\u003eFraction of exhaled nitric oxide\u003c/p\u003e\n \u003cp\u003eAnalysis of variance\u003c/p\u003e\n \u003cp\u003eStandard deviation\u003c/p\u003e\n \u003cp\u003eMaximum percentage of remission\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eConceptualization, E.H.; methodology, J.D.; software, J.D.; validation, J.A., D.G., S.P.; formal analysis, H.G., E.,H; research, H.G.; data curation, J.A.; drafting: preparation of the original draft, A.V.; writing: revision and editing, A.V., S.P.; visualization, J.P., A.LL., J.P.,; supervision, S.P.; project management, S.P. All authors have read and agree with the published version of the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eGlobal Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2024. Updated May 2024. Available from: www.ginasthma.org \u003c/li\u003e\n\u003cli\u003egob.mx [Internet]. Asma y calidad del aire en las ciudades; 14 de septiembre de 2018 [consultado el 25 de enero de 2025]. Disponible en: https://www.gob.mx/comisionambiental/articulos/asma-y-calidad-del-aire-en-las-ciudades?idiom=es#:~:text=Seg\u0026uacute;n%20cifras%20del%20Instituto%20Nacional,humo%20de%20le\u0026ntilde;a%20y%20la\u003c/li\u003e\n\u003cli\u003eBrusselle GG, Koppelman GH. Biologic Therapies for Severe Asthma. New Engl J Med [Internet]. 13 de enero de 2022 [consultado el 25 de enero de 2025];386(2):157-71. 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Disponible en: https://doi.org/10.1056/nejmoa1703501\u003c/li\u003e\n\u003cli\u003eBusse WW, Bleecker ER, FitzGerald JM, Ferguson GT, Barker P, Sproule S, Olsson RF, Martin UJ, Goldman M, Ya\u0026ntilde;ez A, Fern\u0026aacute;ndez M, Tolcachier A, Belloni J, Taborda J, De Salvo M, Maspero J, Victorio C, Navarta MC, Grilli M, Rodr\u0026iacute;guez P, Otaola M, Cambursano V, Malamud P, Stok A, Arce G, Roza O, Scherbovsky F, Elias P, Saez MS, Peters M, Phillips M, Upham J, Gibson P, Thien F, Douglass J, Thomas P, Bardin P, Sajkov D, Hew M, Langton D, Pez A, Fritscher C, Hetzel J, Mattos W, Stelmach R, Antila M, Fernandes AL, Metev H, Ivanov Y, Le L. Long-term safety and efficacy of benralizumab in patients with severe, uncontrolled asthma: 1-year results from the BORA phase 3 extension trial. Lancet Respir Med [Internet]. Enero de 2019 [consultado el 25 de enero de 2025];7(1):46-59. Disponible en: https://doi.org/10.1016/s2213-2600(18)30406-5\u003c/li\u003e\n\u003cli\u003eKorn S, Bourdin A, Chupp G, Cosio BG, Arbetter D, Shah M, Gil EG. Integrated Safety and Efficacy Among Patients Receiving Benralizumab for Up to Five Years. J Allergy Clin Immunol [Internet]. Septiembre de 2021 [consultado el 25 de enero de 2025]. Disponible en: https://doi.org/10.1016/j.jaip.2021.07.058\u003c/li\u003e\n\u003cli\u003eOrtega HG, Liu MC, Pavord ID, Brusselle GG, FitzGerald JM, Chetta A, Humbert M, Katz LE, Keene ON, Yancey SW, Chanez P. Mepolizumab Treatment in Patients with Severe Eosinophilic Asthma. New Engl J Med [Internet]. 25 de septiembre de 2014 [consultado el 25 de enero de 2025];371(13):1198-207. Disponible en: https://doi.org/10.1056/nejmoa1403290\u003c/li\u003e\n\u003cli\u003ePilette C, Canonica GW, Chaudhuri R, Chupp G, Lee FE, Lee JK, Almonacid C, Welte T, Alfonso-Cristancho R, Jakes RW, Maxwell A, Price RG, Howarth P. REALITI-A study: Real-world oral corticosteroid-sparing effect of mepolizumab in severe asthma. J Allergy Clin Immunol [Internet]. Junio de 2022 [consultado el 25 de enero de 2025]. Disponible en: https://doi.org/10.1016/j.jaip.2022.05.042\u003c/li\u003e\n\u003cli\u003ePavord ID, Korn S, Howarth P, Bleecker ER, Buhl R, Keene ON, Ortega H, Chanez P. Mepolizumab for severe eosinophilic asthma (DREAM): a multicenter, double-blind, placebo-controlled trial. Lancet [Internet]. Agosto de 2012 [consultado el 25 de enero de 2025];380(9842):651-9. Disponible en: https://doi.org/10.1016/s0140-6736(12)60988-x\u003c/li\u003e\n\u003cli\u003eBel EH, Wenzel SE, Thompson PJ, Prazma CM, Keene ON, Yancey SW, Ortega HG, Pavord ID. Oral Glucocorticoid-Sparing Effect of Mepolizumab in Eosinophilic Asthma. New Engl J Med [Internet]. 25 de septiembre de 2014 [consultado el 25 de enero de 2025];371(13):1189-97. 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Disponible en: https://doi.org/10.36416/1806-3756/e20210172\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"allergy-asthma-and-clinical-immunology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"aaci","sideBox":"Learn more about [Allergy, Asthma \u0026 Clinical Immunology](http://aacijournal.biomedcentral.com/)","snPcode":"13223","submissionUrl":"https://submission.nature.com/new-submission/13223/3","title":"Allergy, Asthma \u0026 Clinical Immunology","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Asthma, Anti-IL-5, Anti-IL5R, ACQ5","lastPublishedDoi":"10.21203/rs.3.rs-6543940/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6543940/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Asthma is a chronic inflammatory disease of the airways triggered by exogenous antigens. Among its variants, it is crucial to differentiate between severe asthma and asthma, which is difficult to control. Severe asthma is characterized by a lack of response to high doses of inhaled corticosteroids and long-acting beta-2 agonists, whereas difficult-to-control asthma is associated with poor adherence to treatment, inappropriate use of inhalers, or the presence of uncontrolled comorbidities. In recent years, the use of monoclonal antibodies directed against interleukin-5 (anti-IL-5) and its receptor alpha (anti-IL-5R) has proven to be an effective therapeutic option for patients with severe asthma by reducing the number of eosinophils, which may promote disease remission. This study aimed to evaluate clinical improvement and remission in patients with severe asthma treated with anti-IL-5 and anti-IL-5R antibodies over a period of 12 months. A cohort study was conducted with 49 patients who were diagnosed with severe eosinophilic asthma and who did not respond to conventional treatment. During follow-up, medical control was carried out every 3 months via spirometry, eosinophil counts, quality of life scales and disease control. The results revealed an improvement in FEV1 from 3 months of treatment, with statistical significance at 12 months in patients treated with anti-IL-5 and at 9 months in those treated with anti-IL-5R. In addition, better perceptions of asthma control and quality of life were observed, with significant differences at 6 and 12 months. The correlations between spirometry and the ACT, ACQ and AQLQ reflect a progressive recovery of well-being and function. Finally, the remission rate was 41.1% with anti-IL-5 therapy and 47.3% with anti-IL-5R therapy after one year of follow-up. These findings support the efficacy of treatment with anti-IL-5 and anti-IL-5R in improving severe asthma control and patients' quality of life, suggesting their key role in disease remission.","manuscriptTitle":"Anti-IL-5 and anti-IL-5 receptor therapy significantly improves quality of life and FEV1 values in patients with severe asthma","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-16 11:55:02","doi":"10.21203/rs.3.rs-6543940/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-06-17T03:54:10+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-06-16T17:31:03+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-22T15:32:50+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"128310532662709133483500396933882987270","date":"2025-05-18T09:14:53+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"8540453586548076333546614304008445045","date":"2025-05-13T06:32:03+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-05-13T03:39:43+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-04-30T09:47:50+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-30T09:43:09+00:00","index":"","fulltext":""},{"type":"submitted","content":"Allergy, Asthma \u0026 Clinical Immunology","date":"2025-04-28T05:02:19+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"allergy-asthma-and-clinical-immunology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"aaci","sideBox":"Learn more about [Allergy, Asthma \u0026 Clinical Immunology](http://aacijournal.biomedcentral.com/)","snPcode":"13223","submissionUrl":"https://submission.nature.com/new-submission/13223/3","title":"Allergy, Asthma \u0026 Clinical Immunology","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"571f649f-268a-4c4e-9c76-5a2ff7a138ae","owner":[],"postedDate":"May 16th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-08-18T16:05:45+00:00","versionOfRecord":{"articleIdentity":"rs-6543940","link":"https://doi.org/10.1186/s13223-025-00979-y","journal":{"identity":"allergy-asthma-and-clinical-immunology","isVorOnly":false,"title":"Allergy, Asthma \u0026 Clinical Immunology"},"publishedOn":"2025-08-13 15:57:46","publishedOnDateReadable":"August 13th, 2025"},"versionCreatedAt":"2025-05-16 11:55:02","video":"","vorDoi":"10.1186/s13223-025-00979-y","vorDoiUrl":"https://doi.org/10.1186/s13223-025-00979-y","workflowStages":[]},"version":"v1","identity":"rs-6543940","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6543940","identity":"rs-6543940","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}