Low levels of miR-143-3p are associated with severe chronic rhinosinusitis with nasal polyps.

microRNAs (miRNAs) are small, single-stranded, non-coding RNA molecules that regulate post-transcriptional gene expression. Accumulating evidence suggests their involvement in regulating various biological and pathological processes, including inflammation. Studies have revealed distinct expression patterns of miRNAs in Chronic Rhinosinusitis with (CRSwNP) and without (CRSsNP) nasal polyps (1). Specifically, miR-155 and miR-21 have been observed to be upregulated in CRSwNP, increasing and attenuating the expression of pro-inflammatory cytokines, respectively (2,3). Conversely, the downregulation of miR-34, miR-449, and members of the miR-200 family has been associated with impaired ciliogenesis and the regulation of epithelial-mesenchymal transition, respectively (4,5). Nonetheless, the direct role of miRNAs in CRSwNP is still being investigated.

Impact of climate change-related environmental factors on the allergens production and the epidemiology and severity of allergic pathologies.

BACKGROUND: Allergic disease affects up to 40% of the global adult population, a proportion that is increasing with environmental changes related to global warming. METHODS: We undertook a systematic review of the literature to identify and evaluate the current evidence of the impact of climate change-related environmental factors on the allergen production and the epidemiology and severity of allergic pathologies. PECO criteria were established and guided the literature searches of the PubMed and Cochrane databases (Jan 1, 2016 to Dec 31, 2021). Study outcomes were categorized and grouped to facilitate data synthesis. Outcomes were classified as significant (statistical significance <0.05), non-significant (p>0.05) or undetermined (p value not reported). Study quality was assessed using MMAT analysis. RESULTS: Of 195 studies, 40 were considered relevant and 9 of them provided data to be included in the data quantitative synthesis. Environmental factors, including the presence of pollutants, temperature, and drought, influenced the type, volume, and timing of exposure to local aeroallergens. The most relevant environmental factor was the presence of environmental pollutants, of which tropospheric ozone was the most frequently associated to changes in allergen production, prevalence, and severity of allergic disease. Also, several publications demonstrated the impact of environmental factors on the healthcare burden. CONCLUSIONS: Climate-change related environmental factors increased allergic disease in terms of prevalence, severity, and healthcare burden due to alterations in allergen exposure (volume and type) with the presence of pollutants such as ozone being the most commonly reported driver of such increase.

Differences in molecular sensitization profiles between a Spanish and Latin American mite allergic patients.

BACKGROUND AND OBJECTIVE: To analyze the sensitization pattern to Dermatophagoides pteronyssinus and to associate the diagnostic findings and clinical severity in 218 allergic patients from two different continents. METHODS: Mite allergic patients were recruited by the Allergology departments from Latin America (n=88: Colombia, Costa Rica and Guatemala) and Spain (N=130). All patients had allergic rhinitis with or without asthma and positive skin prick test results to D. pteronyssinus. Specific IgE levels to D. pteronyssinus, D. farinae, Der p 1, Der p 2, and Der p 23 were quantified by ImmunoCAP system (ThermoFisher Scientific). Allergenic profile was also determined by western blot. Comparative Statistical analysis was performed by GraphPad software. RESULTS: Patients recognized most frequently Der p 2 (79%) followed by Der p 1 (73%), and Der p 23 (69%) allergens. The percentage of asthmatic patients increases with the number of sensitizations however none statistically significant differences were found. Interestingly, asthmatic patients presented the highest median levels of total IgE and specific IgE levels of D. pteronyssinus and molecular allergens, mainly Der p 2. Analysing the two different populations, Spanish patients were predominantly sensitized to Der p 2 (88.46%) and Der p 1 (83.84%), whereas Latin American population were more sensitized to Der p 23. CONCLUSION: Our data support the relevance of Der p 2 in mite allergy as the major allergen, with the high number of patients sensitized to it and its importance in the development of asthma. Sensitization to Der p 23 was more important in Latin America.

[Reference levels of thyroid hormones in pregnant woman from Guadalajara]. / Valores de referencia de hormonas tiroideas en la población de gestantes de Guadalajara.

INTRODUCTION: Thyroid dysfunction during gestation impacts on maternal-fetal health and may influence the neurocognitive development of the child. Thyroid physiology changes during pregnancy and requires the establishment of specific reference levels per trimester and for each population and method. The objectives of our study were to analyse thyroid function throughout pregnancy and to establish reference levels for TSH and T4L in each trimester for our population and methodology. MATERIAL AND METHODS: Prospective analytical study of 598 pregnant women from March 2018 to October 2020. TSH, T4L, T3L, ATPO and ATG were determined in all of them. A total of 151 pregnant women were excluded due to positive thyroid immunity, previous thyroid disease in treatment with levothyroxine, twin pregnancy, diagnosis of hypothyroidism and hyperthyroidism in the request or absence of some of the parameters studied, with a reference population of 447 pregnant women. RESULTS: The reference levels for TSH were 0.07-3.14mIU/L for the first, 0.66-3.21mIU/L for the second and 0.52-2.97mIU/L for the third trimester. Reference levels for T4L were 0.81-1.19ng/dL for the first, 0.71-1.07ng/dL for the second and 0.69-1.06ng/dL for the third trimester. CONCLUSIONS: The reference levels for TSH and T4L obtained in this study differ from those used for the general population, which may have led to misclassification errors and unnecessary treatment in pregnant women.

Prevalence of asthma in Catalonia (Spain): a retrospective, large-scale population-based study.

BACKGROUND AND OBJECTIVE: Asthma epidemiology reports an estimated global prevalence of about 4.3-8.6% in adults, with last differences among geographical regions. This study analyses a more significant population of asthma patients (473,737 individuals).To study the prevalence of medical diagnosis of asthma, overall and by age, gender, and disease severity, as well as comorbidities and type 2 biomarkers, and undergo medical treatments of a retrospective population-based asthma cohort from Catalonia (Spain). METHODS: Individuals with a diagnosis of asthma established by medical records at different healthcare levels (primary, hospital, and emergency) from the Catalan Health System (CHS) were included. Socio-demographic characteristics, prevalence, overall and by age and gender, disease severity, comorbidities, and biomarkers of type-2 inflammation were evaluated, together with appropriate medical treatment. RESULTS: The overall diagnosed asthma prevalence in the population of Catalonia was 6.3%, where patients mainly had mild asthma (5.3%) and were significantly higher in females (6.8%) than males (5.7%). By age groups, asthma was more prevalent in boys and young men adults; however, being more prevalent in females above the age of 30y. The prevalence of severe asthma was 0.4%, 42.6% had uncontrolled asthma, and a high proportion (84.2%) were under systemic corticosteroid prescription. As expected, SABAs were the most prescribed drug (62.6%), followed by systemic corticosteroids (43.3%). More than half (53.8%) of patients showed type 2 inflammation. CONCLUSION: Asthma prevalence in Catalonia is similar to other areas studied in Spain, with a high prevalence in women and of T2 asthma.

Prevalence of Atopic Dermatitis in the adult population of Catalonia (Spain): a retrospective, large-scale population-based study.

BACKGROUND AND OBJECTIVES: Studies on the prevalence of Atopic Dermatitis (AD) for the adult cohort in general-based populations are scarce worldwide. We performed a retrospective population-based observational cohort study of 537,098 adult patients diagnosed with AD in Catalonia (Spain), a larger population than in previous studies. To study the prevalence of AD generally by age, gender, disease severity, multi-morbidities, and serum total Immunoglobin E (tIgE) and undergo appropriate medical treatment (AMT) for the Catalan population. METHODS: Adult individuals (≥18 years old) diagnosed with AD by medical records at different health care levels (primary, hospital, emergency) from the Catalan Health System (CHS) were included. Statistical analyses were conducted to evaluate socio-demographic characteristics, prevalence, multi-morbidities, serum tIgE and AMT. RESULTS: The overall diagnosed AD prevalence in the adult Catalan population was 8.7%, being higher for the non-severe (8.5%) than for the severe (0.2%) populations and females (10.1%) than males (7.3%). Topical corticosteroids were the most prescribed drug (66.5%), and the use of all prescribed treatments was higher in severe AD patients, especially systemic corticosteroids (63.8%) and immunosuppressant agents (60.7%). More than half (52.2%) of severe AD patients reported serum tIgE ≥ 100 KU/L, and higher values were observed for those with multi-morbidities. Acute bronchitis (13.7%), allergic rhinitis (12.1%), and asthma (8.6%) were the most frequent comorbid respiratory diseases. CONCLUSIONS: Our study provides new and robust evidence of AD´s prevalence and related characteristics in adults using a large-scale population-based study and a more significant cohort of individuals.

Impact of Asthma Inhalers on Global Climate: A Systematic Review of Their Carbon Footprint and Clinical Outcomes in Spain.

BACKGROUND: Pressurized metered-dose inhalers (pMDIs) exert an environmental impact resulting from CO2 emissions. Therapeutic alternatives with less environmental impact are widely used. Nevertheless, the choice of device and appropriate therapy should meet the clinical needs and the characteristics of the patient. OBJECTIVE: The primary objective was to estimate the impact of pMDIs prescribed for any indication on annual CO2 emissions in Spain.The secondary objective was to evaluate the potential impact of switching pMDIs to dry-powder inhalers (DPIs) in patients with asthma. METHODS: A systematic review of the evidence published during 2010-2021 was carried out. Average annual CO2 emissions of DPIs and pMDIs were calculated in 2 scenarios: the current situation and a hypothetical situation involving a switch from all pMDIs to DPIs. The impact of the switch on clinical outcomes was also evaluated. RESULTS: The total value of CO2-eq/year due to DPIs and pMDIs accounted for 0.0056% and 0.0909%, respectively, of total emissions in Spain. In the event of switching pMDIs to DPIs, except those used for rescue medication, the percentages were 0.0076% and 0.0579%. The evaluation of efficacy, handling, satisfaction, safety, and use of health care resources was not conclusive. CONCLUSIONS: Current CO2 emissions by pMDIs account for a small percentage of the total CO2 footprint in Spain. Nevertheless, there is a need for research into new and more sustainable devices. Suitability and patient clinical criteria such as age and inspiratory flow should be prioritized when prescribing an inhaler.

Weight Loss and Vitamin D Improve Hyporesponsiveness to Corticosteroids in Obese Asthma.

BACKGROUND AND OBJECTIVES: Obesity negatively impacts on the response of asthma patients to inhaled corticosteroids. The mechanisms underlying this impact are unknown. Objective: To demonstrate that the poor response to inhaled corticosteroids in obese asthma patients is associated with impaired anti-inflammatory activity of corticosteroids and vitamin D deficiency, both of which are improved by weight loss. METHODS: The study population comprised 23 obese asthma patients (OA) (18 females; median (IQR) age 56 [51-59] years), 14 nonobese asthma patients (NOA) (11 females; 53 [43-60] years), 15 obese patients (OP) (13 females; 47 [45-60] years), and 19 healthy controls (HC) (14 females; 43 [34-56] years). Ten OA and 11 OP were evaluated at baseline (V1) and 6 months after bariatric surgery (V2). Corticosteroid response was measured using dexamethasone-induced inhibition of peripheral blood mononuclear cell (PBMC) proliferation. Lung function and serum levels of leptin, adiponectin, and vitamin D were measured at V1 and V2. RESULTS: We found a reduced response to dexamethasone in PBMCs of OP and OA with respect to NOA and HC; this inversely correlated with the adiponectin/leptin ratio and vitamin D levels. Bariatric surgery improved corticosteroid responses in OP and OA and normalized the adiponectin/leptin ratio and vitamin D levels. Exposure of PBMCs to vitamin D potentiated the antiproliferative effects of corticosteroids. Dexamethasone and vitamin D induced similar MKP1 expression in OP and OA. CONCLUSION: The efficacy of weight loss to improve symptoms and lung function in OA may be due, at least in part, to the recovered anti-inflammatory effects of corticosteroids. Vitamin D deficiency may contribute to corticosteroid hyporesponsiveness in OA.

Improvement in Olfaction in Patients With CRSwNP and Severe Asthma Taking Anti-IgE and Anti-IL-5 Biologics: A Real-Life Study.

BACKGROUND AND OBJECTIVES: Chronic rhinosinusitis with nasal polyps (CRSwNP), which is characterized by partial loss of smell (hyposmia) or total loss of smell (anosmia), is commonly associated with asthma and/or nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD). CRSwNP worsens disease severity and quality of life. The objective of this real-world study was to determine whether biological treatments prescribed for severe asthma can improve olfaction in patients with CRSwNP. A further objective was to compare the improvement in in olfaction in N-ERD and non-N-ERD subgroups. METHODS: We performed a multicenter, noninterventional, retrospective, observational study of 206 patients with severe asthma and CRSwNP undergoing biological treatment (omalizumab, mepolizumab, benralizumab, or reslizumab). RESULTS: Olfaction improved after treatment with all 4 monoclonal antibodies (omalizumab [35.8%], mepolizumab [35.4%], reslizumab [35.7%], and benralizumab [39.1%]), with no differences between the groups. Olfaction was more likely to improve in patients with atopy, more frequent use of short-course systemic corticosteroids, and larger polyp size. The proportion of patients whose olfaction improved was similar between the N-ERD (37%) and non-N-ERD (35.7%) groups. CONCLUSIONS: This is the first real-world study to compare improvement in olfaction among patients undergoing long-term treatment with omalizumab, mepolizumab, reslizumab, or benralizumab for severe asthma and associated CRSwNP. Approximately 4 out of 10 patients reported a subjective improvement in olfaction (with nonsignificant differences between biologic drugs). No differences were found for improved olfaction between the N-ERD and non-N-ERD groups.

Economic Consequences of the Overuse of Short-Acting ß-Adrenergic Agonists in the Treatment of Asthma in Spain.

BACKGROUND AND OBJECTIVE: To determine the relationship between short-acting ß-adrenergic agonist (SABA) overuse and health care resource use and costs in asthma patients in routine clinical practice. METHODS: A longitudinal retrospective study was conducted in Spanish primary and specialized care centers using the BIG-PAC medical records database. The study population comprised asthma patients ≥12 years of age who attended ≥2 consultations during 2017 and had 1-year follow-up data available. The main outcomes were demographics, comorbidities, medication, and clinical and health care resource use and costs. The relationship between SABA overuse and health care costs and between asthma severity and health care costs was determined. RESULTS: The SABA use IN Asthma (SABINA) study included 39 555 patients, with a mean (SD) age of 49.8 (20.7) years (64.2% female). The Charlson comorbidity index was 0.7 (1.0). SABA overuse (≥3 canisters/y) was 28.7% (95%CI, 27.7-29.7), with a mean of 3.3 (3.6) canisters/y. Overall, 5.1% of patients were prescribed ≥12 canisters/y. SABA overuse was correlated with health care costs (ρ=0.621; P<.001). The adjusted mean annual cost/patient according to the Global Initiative for Asthma (GINA 2019) classification of asthma severity was €2231, €2345, €2735, €3473, and €4243 for steps 1-5, respectively (P<.001). Regardless of asthma severity, SABA overuse yielded a significant increase in health care costs per patient and year (€5702 vs €1917, P<.001) compared with recommended use (<2 canisters/y). CONCLUSION: SABA overuse yields high costs for the Spanish National Health System. Costs increased with severity of asthma.

Exacerbations Among Patients With Asthma Are Largely Dependent on the Presence of Multimorbidity.

BACKGROUND AND OBJECTIVE: Comorbidities can influence asthma control and promote asthma exacerbations (AEs). However, the impact of multimorbidity in AEs, assessed based on long-term follow-up of patients with asthma of different degrees of severity, has received little attention in real-life conditions. To describe the epidemiological and clinical characteristics and predictors of AEs in patients who had presented at least 1 AE in the previous year in the MEchanism of Genesis and Evolution of Asthma (MEGA) cohort. METHODS: The work-up included a detailed clinical examination, pulmonary function testing, fractional exhaled nitric oxide (FeNO), blood counts, induced sputum, skin prick-tests, asthma questionnaires, and assessment of multimorbidity. The number of moderate-severe AEs in the preceding year was registered for each patient. RESULTS: The study population comprised 486 patients with asthma (23.7% mild, 35% moderate, 41.3% severe). Disease remained uncontrolled in 41.9%, and 47.3% presented ≥1 moderate-severe AE, with a mean (SD) annual exacerbation rate of 0.47 (0.91) vs 2.11 (2.82) in mild and severe asthma, respectively. Comorbidity was detected in 56.4% (66.6% among those with severe asthma). Bronchiectasis, chronic rhinosinusitis with nasal polyps, atopy, psychiatric illnesses, hyperlipidemia, and hypertension were significantly associated with AEs. No associations were found for FeNO, blood eosinophils, or total serum IgE. Sputum eosinophilia and a high-T2 inflammatory pattern were significantly associated with AEs. Multivariable regression analysis showed a significant association with asthma severity, uncontrolled disease, and low prebronchodilator FEV1/FVC. CONCLUSION: Our study revealed a high frequency of AE in the MEGA cohort. This was strongly associated with multimorbidity, asthma severity, poor asthma control, airflow obstruction, higher sputum eosinophils, and a very high-T2 inflammatory pattern.

Quantitative assessment of Campylobacter spp. levels with real-time PCR methods at different stages of the broiler food chain.

The importance of thermotolerant Campylobacter spp. as a food-borne pathogen continues to increase and there is a great need for rapid quantitative results in routine diagnostics. However, currently, only the culture-based ISO method is authorized for use in the context of official food control. The present study therefore aimed to assess the suitability of a qPCR method for a rapid quantitative determination of Campylobacter spp. at different stages in the poultry production chain and its equivalence with the culture-based method. Samples from two processors were collected and evaluated both separately and together. Censored regression (Tobit) models have been used to establish a relationship between Campylobacter qPCR counts on the carcasses and explanatory variables of processor and meat counts. Further, correlations of qPCR Campylobacter spp. counts at the different stages of production were calculated. In addition, the comparative data between microbiological enumeration and qPCR results were statistically analyzed. In the correlation calculation of the qPCR results, a highly significant relationship between the Campylobacter spp. counts of the neck skin samples to breast fillet and leg samples could be calculated, indicating a good prediction of Campylobacter spp. loads in these samples. The intercalating dye ethidium monoazide (EMA) was used to see whether the correlations between microbiological counts and qPCR results were improved by pretreating fecal and cecal samples before qPCR analysis. It was shown that the observed values of scatter plots between the qPCR-based and the culture-based methods were strongly correlated. However, on average, the qPCR results were two log10 CFU/mL levels higher than the microbiological counts. However, the classical culture-based method for food hygiene risk assessment cannot be replaced one-to-one by the qPCR or EMA-qPCR. The qPCR method can rather be used for the rapid identification of particularly highly contaminated flocks.

Weight Loss and Vitamin D Improve Hyporesponsiveness to Corticosteroids in Obese Asthma

Background: Obesity negatively impacts on the response of asthma patients to inhaled corticosteroids. The mechanisms underlying this impact are unknown. Objective: To demonstrate that the poor response to inhaled corticosteroids in obese asthma patients is associated with impaired anti-inflammatory activity of corticosteroids and vitamin D deficiency, both of which are improved by weight loss. Methods: The study population comprised 23 obese asthma patients (OA) (18 females; median (IQR) age 56 [51-59] years), 14 nonobese asthma patients (NOA) (11 females; 53 [43-60] years), 15 obese patients (OP) (13 females; 47 [45-60] years), and 19 healthy controls (HC) (14 females; 43 [34-56] years). Ten OA and 11 OP were evaluated at baseline (V1) and 6 months after bariatric surgery (V2). Corticosteroid response was measured using dexamethasone-induced inhibition of peripheral blood mononuclear cell (PBMC) proliferation. Lung function and serum levels of leptin, adiponectin, and vitamin D were measured at V1 and V2. Results: We found a reduced response to dexamethasone in PBMCs of OP and OA with respect to NOA and HC; this inversely correlated with the adiponectin/leptin ratio and vitamin D levels. Bariatric surgery improved corticosteroid responses in OP and OA and normalized the adiponectin/leptin ratio and vitamin D levels. Exposure of PBMCs to vitamin D potentiated the antiproliferative effects of corticosteroids. Dexamethasone and vitamin D induced similar MKP1 expression in OP and OA. (AU)

Antecedentes: La obesidad tiene un impacto negativo en la respuesta del asma a los corticosteroides inhalados por mecanismos desconocidos. Objetivo: Demostrar que la mala respuesta a los corticosteroides inhalados en pacientes obesos asmáticos se asocia con una actividad antiinflamatoria alterada de los corticosteroides, así como también a la deficiencia de vitamina D, ambos mejorados por la pérdida de peso. Métodos: 23 obesos asmáticos (OA) (18 mujeres; mediana de edad [rango intercuartílico] 56 [51-59] años), 14 asmáticos no obesos (NOA) (11 mujeres; 53 [43-60] años), 15 obesos (O) (13 mujeres; 47 [45-60] años), y 19 controles sanos (HC) (14 mujeres; 43 [34-56] años) fueron incluidos. Se evaluaron 10 pacientes OA y 11 O al inicio (V1) y seis meses después (V2) de cirugía bariátrica. La respuesta a los corticosteroides se midió mediante la inhibición con dexametasona de la proliferación de células mononucleares de sangre periférica (PBMC). La función pulmonar, los niveles séricos de leptina, adiponectina y vitamina D se midieron en V1 y V2. Resultados: Encontramos una respuesta reducida a la dexametasona en PBMC de pacientes O y OA con respecto a los NOA y HC, que se correlacionó de forma inversamente proporcional con la relación adiponectina/leptina y los niveles de vitamina D. La cirugía bariátrica mejoró las respuestas de los corticosteroides en los grupos de pacientes O y OA, y normalizó la relación adiponectina/leptina y los niveles de vitamina D. La exposición de las PBMC a la vitamina D potenció los efectos antiproliferativos de los corticosteroides. La dexametasona y la vitamina D indujeron una expresión similar de MKP-1 en los pacientes O y OA. (AU)

Economic Consequences of the Overuse of Short-Acting ß-Adrenergic Agonists in the Treatment of Asthma in Spain

Objective: To determine the relationship between short-acting ß-adrenergic agonist (SABA) overuse and health care resource use and costs in asthma patients in routine clinical practice. Methods: A longitudinal retrospective study was conducted in Spanish primary and specialized care centers using the BIG-PAC medical records database. The study population comprised asthma patients ≥12 years of age who attended ≥2 consultations during 2017 and had 1-year follow-up data available. The main outcomes were demographics, comorbidities, medication, and clinical and health care resource use and costs. The relationship between SABA overuse and health care costs and between asthma severity and health care costs was determined. Results: The SABA use IN Asthma (SABINA) study included 39 555 patients, with a mean (SD) age of 49.8 (20.7) years (64.2% female). The Charlson comorbidity index was 0.7 (1.0). SABA overuse (≥3 canisters/y) was 28.7% (95%CI, 27.7-29.7), with a mean of 3.3 (3.6) canisters/y. Overall, 5.1% of patients were prescribed ≥12 canisters/y. SABA overuse was correlated with health care costs (ρ=0.621; P<.001). The adjusted mean annual cost/patient according to the Global Initiative for Asthma (GINA 2019) classification of asthma severity was €2231, €2345, €2735, €3473, and €4243 for steps 1-5, respectively (P<.001). Regardless of asthma severity, SABA overuse yielded asignificant increase in health care costs per patient and year (€5702 vs €1917, P<.001) compared with recommended use (<2 canisters/y). Conclusion: SABA overuse yields high costs for the Spanish National Health System. Costs increased with severity of asthma (AU)

Objetivo: Determinar la relación entre la sobreutilización de agonistas beta adrenérgicos de acción corta (SABA) en pacientes con asma y el uso y coste de recursos sanitarios en la práctica clínica rutinaria. Métodos: Se realizó un estudio longitudinal retrospectivo en atención primaria y especializada en España, en el que se utilizó la base de datos de registros médicos BIG-PAC®. Se incluyeron pacientes con asma ≥12 años que asistieron a ≥2 consultas durante 2017 y con datos disponibles del seguimiento durante 1 año. Los principales resultados analizados fueron características demográficas, comorbilidades, medicaciones, y el uso y coste de recursos clínicos y sanitarios. Se determinó la relación de los costes sanitarios tanto con la sobreutilización de SABA como con la severidad del asma. Resultados: Este estudio sobre el uso de SABA en asma (SABINA, del inglés “SABA use IN Asthma”) incluyó a 39.555 pacientes, con una edad media (DE, desviación estándar) de 49,8 años (20,7); 64.2% fueron mujeres. La media del índice de comorbilidad Charlson fue 0,7 (1,0). La sobreutilización de SABA (≥3 envases/año) fue del 28,7% (IC95%: 27,7–29,7), con una media global de 3,3 envases (3,6) /año. En total, el 5,1% de los pacientes fueron prescritos con ≥12 envases/año. La sobreutilización de SABA correlacionó con los costes sanitarios (ρ = 0,621; p < 0,001). El coste medio anual/paciente según la clasificación de severidad del asma de la Global Initiative for Asthma (GINA 2019) fue de 2.231 €, 2.345 €, 2.735 €, 3.473 €, y 4.243 €, para los pasos 1-5, respectivamente (p < 0,001) (AU)