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Contemporary data on the availability, cost and affordability of essential medicines for chronic respiratory diseases (CRDs) across low-income and middle-income countries (LMICs) are missing, despite most people with CRDs living in LMICs. Cross-sectional data for seven CRD medicines in pharmacies, healthcare facilities and central medicine stores were collected from 60 LMICs in 2022-2023. Medicines for symptomatic relief were widely available and affordable, while preventative treatments varied widely in cost, were less available and largely unaffordable. There is an urgent need to address these issues if the Sustainable Development Goal 3 is to be achieved for people with asthma by 2030.
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Países en Desarrollo , Medicamentos Esenciales , Accesibilidad a los Servicios de Salud , Humanos , Estudios Transversales , Medicamentos Esenciales/economía , Medicamentos Esenciales/provisión & distribución , Medicamentos Esenciales/uso terapéutico , Enfermedad Crónica , Accesibilidad a los Servicios de Salud/economía , Costos de los Medicamentos , Enfermedades Respiratorias/tratamiento farmacológico , Enfermedades Respiratorias/economíaRESUMEN
The widespread use of systemic corticosteroids (SCS) in asthma is associated with significant comorbidities and mortality. A dose-response relationship for cumulative SCS exposure with most adverse outcomes began at cumulative exposures of 1.0-<2.5 g, equivalent to four lifetime SCS courses. The purpose of creating the SCS credit concept was to increase awareness of the risks of SCS exposure and to promote better therapeutic alternatives. Consuming the lifetime SCS credit of 1.5 g/yr significantly increased morbidity and mortality.
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INTRODUCTION: Biomarkers are used to select biologic therapies for patients with severe asthma, but not to regularly adjust therapy, especially oral corticosteroids (OCS). OBJECTIVE: Our goal was to test the efficacy of an algorithm to guide the titration of OCS using blood eosinophil count and fraction of exhaled nitric oxide (FeNO) levels. DESIGN, PARTICIPANTS, INTERVENTIONS AND SETTING: This proof-of-concept prospective randomised controlled trial assigned adult participants with severe uncontrolled asthma (n=32) to biomarker-based management (BBM) where OCS dose was adjusted based on a composite biomarker score comprised of blood eosinophil count and FeNO, or a standard best practice (SBP) arm. The study was conducted at the Hunter Medical Research Institute, Newcastle, Australia. Participants were recruited from the local Severe Asthma Clinic and were blinded to their study allocation. MAIN OUTCOME: The coprimary outcomes were number of severe exacerbations and time to first severe exacerbation assessed over 12 months. RESULTS: There was a longer median time to first severe exacerbation with BBM, although not significant (295 vs 123 days, Adj. HR: 0.714; 95% CI: 0.25 to 2.06; p=0.533). The relative risk of a severe exacerbation in BBM (n=17) vs SBP (n=15) was 0.88 (Adj.; 95% CI: 0.47 to 1.62; p=0.675) with a mean exacerbation rate per year of 1.2 and 2.0, respectively. There was a significant reduction in the proportion of patients requiring an emergency department (ED) visit using BBM (OR 0.09, 95% CI: 0.01 to 0.91; p=0.041). There was no difference in the cumulative OCS dose used between the two groups. CONCLUSION: A treatment algorithm to adjust OCS using blood eosinophil count and FeNO is feasible in a clinical setting and resulted in a reduced odds of an ED visit. This warrants further study to optimise the use of OCS in the future. TRIAL REGISTRATION NUMBER: This trial was registered with the Australia and New Zealand Clinical Trials Registry (ACTRN12616001015437).
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Antiasmáticos , Asma , Adulto , Humanos , Estudios Prospectivos , Óxido Nítrico , Asma/tratamiento farmacológico , Corticoesteroides/uso terapéutico , Inflamación/tratamiento farmacológico , Biomarcadores , Antiasmáticos/uso terapéuticoRESUMEN
INTRODUCTION: Asthma is a complex disease with heterogeneous expression/severity. There is growing interest in defining asthma endotypes consistently associated with different responses to therapy, focusing on type 2 inflammation (Th2) as a key pathological mechanism. Current asthma endotypes are defined primarily by clinical/laboratory criteria. Each endotype is likely characterised by distinct molecular mechanisms that identify optimal therapies. METHODS: We applied unsupervised (without a priori clinical criteria) principal component analysis on sputum airway cells RNA-sequencing transcriptomic data from 19 asthmatics from the Severe Asthma Research Program at baseline and 6-8 weeks follow-up after a 40 mg dose of intramuscular corticosteroids. We investigated principal components PC1, PC3 for association with 55 clinical variables. RESULTS: PC3 was associated with baseline Th2 clinical features including blood (rank-sum p=0.0082) and airway (rank-sum p=0.0024) eosinophilia, FEV1 change (Kendall tau-b R=-0.333 (-0.592 to -0.012)) and follow-up FEV1 albuterol response (Kendall tau-b R=0.392 (0.079 to 0.634)). PC1 with blood basophlia (rank-sum p=0.0191). The top 5% genes contributing to PC1, PC3 were enriched for distinct immune system/inflammation ontologies suggesting distinct subject-specific clusters of transcriptomic response to corticosteroids. PC3 association with FEV1 change was reproduced in silico in a comparable independent 14-subject (baseline, 8 weeks after daily inhaled corticosteroids (ICS)) airway epithelial cells microRNAome dataset. CONCLUSIONS: Transcriptomic PCs from this unsupervised methodology define molecular pharmacogenomic endotypes that may yield novel biology underlying different subject-specific responses to corticosteroid therapy in asthma, and optimal personalised asthma care. Top contributing genes to these PCs may suggest new therapeutic targets.
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Asma , Eosinófilos , Corticoesteroides/uso terapéutico , Asma/tratamiento farmacológico , Asma/genética , Basófilos/patología , Eosinófilos/patología , Humanos , Inflamación , Pulmón , Esputo , Esteroides/uso terapéuticoRESUMEN
BACKGROUND: Infants and young children might be particularly susceptible to the potential side effects from inhaled corticosteroid (ICS) on height and bone mineral content (BMC), but this has rarely been studied in long-term prospective studies. METHODS: Children from two Copenhagen Prospective Studies on Asthma in Childhood cohorts were included. ICS use was registered prospectively from birth to age 6 and the cumulative dose was calculated. Primary outcomes were height and BMC from dual-energy X-ray absorptiometry (DXA) scans at age 6. RESULTS: At age 6, a total of 930 children (84%) from the cohorts had a valid height measurement and 792 (71%) had a DXA scan. 291 children (31%) received a cumulated ICS dose equivalent to or above 10 weeks of standard treatment before age 6. We found an inverse association between ICS use and height, -0.26 cm (95% CI: -0.45 to -0.07) per 1 year standard treatment from 0 to 6 years of age, p=0.006. This effect was mainly driven by children with ongoing treatment between age 5 and 6 years (-0.31 cm (95% CI: -0.52 to -0.1), p=0.004), while there was no significant association in children who stopped treatment at least 1 year before age 6 (-0.09 cm (95% CI: -0.46 to 0.28), p=0.64). There was no association between ICS use and BMC at age 6. CONCLUSIONS: ICS use in early childhood was associated with reduced height at age 6 years but only in children with continued treatment in the sixth year of life.
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Antiasmáticos , Asma , Administración por Inhalación , Corticoesteroides/uso terapéutico , Antiasmáticos/uso terapéutico , Asma/complicaciones , Asma/tratamiento farmacológico , Densidad Ósea , Niño , Preescolar , Humanos , Estudios ProspectivosRESUMEN
BACKGROUND: several biological treatments have become available for management of severe asthma. There is a significant overlap in the indication of these treatments with lack of consensus on the first-line biologic choice and switching practice in event of treatment failure. AIMS: to evaluate outcomes of biologic treatments through analysis of the UK Severe Asthma Registry (UKSAR), and survey of the UK severe asthma specialists' opinion. METHODS: patients registered in the UKSAR database and treated with biologics for severe asthma in the period between January 2014 and August 2021, were studied to explore biologic treatments practice. This was complemented by survey of opinion of severe asthma specialists. RESULTS: a total of 2,490 patients from 10 severe asthma centres were included in the study (mean age 51.3 years, 61.1% female, mean BMI 30.9kg/m2 ). Biologics use included mepolizumab 1,115 (44.8%), benralizumab 925 (37.1%), omalizumab 432 (17.3%), dupilumab 13 (0.5%), and reslizumab 5 (0.2%). Patients on omalizumab were younger and had earlier age of onset asthma than those prescribed mepolizumab or benralizumab. Patients prescribed mepolizumab and benralizumab had similar clinical characteristics. Those on benralizumab were more likely to continue treatment at approximately one year follow up (93.9%), than those on mepolizumab (80%), or omalizumab (69.6%). The first choice biologic differed between centres and changed over the study time period. Experts' opinion also diverged in terms of biologic initiation choice and switching practice. CONCLUSION: We observed significant variation and divergence in the prescribing practices of biologics in severe asthma that necessitates further research and standardisation.
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BACKGROUND: The relationship between asthma and vitamin D deficiency has been known for some time. However, interventional studies conducted in this regard have shown conflicting results. OBJECTIVE: To evaluate the efficacy of vitamin D supplementation in asthmatic patients in improving the degree of control of asthma. METHODS: Randomised, triple-blind, placebo-controlled, parallel-group study in adult asthmatic patients with serum 25-hydroxyvitamin-D3 <30 ng/mL. The intervention group received oral supplementation with 16 000 IU of calcifediol per week, and the control group had placebo added to their usual asthma treatment. The study period was 6 months. The primary endpoint was the degree of asthma control as determined by the asthma control test (ACT). Secondary endpoints included quality of life measured using the mini Asthma Quality of Life Questionnaire, the number of asthma attacks, oral corticosteroid cycles, the dose of inhaled corticosteroids, number of emergency visits, unscheduled consultations with the primary care physician and hospitalisations for asthma. RESULTS: One hundred and twelve patients were randomised (mean age 55 years, with 87 (78%) being women). Of the 112 patients, 106 (95%) completed the trial. Half the patients (56) were assigned to the intervention group and the other half to the control group. A statistically significant clinical improvement was observed in the intervention group (+3.09) compared with the control group (-0.57) (difference 3.66 (95% CI 0.89 to 5.43); p<0.001) as measured using ACT scores. Among the secondary endpoints, a significant improvement in the quality of life was found in the intervention group (5.34), compared with the control group (4.64) (difference 0.7 (95% CI 0.15 to 1.25); p=0.01). CONCLUSION: Among adults with asthma and vitamin D deficiency, supplementation with weekly oral calcifediol compared with placebo improved asthma control over 6 months. Further research is needed to assess long-term efficacy and safety. TRIAL REGISTRATION NUMBER: NCT02805907.
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Asma/prevención & control , Deficiencia de Vitamina D/tratamiento farmacológico , Vitamina D/administración & dosificación , Corticoesteroides/uso terapéutico , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Encuestas y CuestionariosRESUMEN
BACKGROUND: Severe asthma is a chronic lung disease characterised by inflammation, airway hyperresponsiveness (AHR) and airway remodelling. The molecular mechanisms underlying uncontrolled airway smooth muscle cell (aSMC) proliferation involved in pulmonary remodelling are still largely unknown. Small G proteins of the Rho family (RhoA, Rac1 and Cdc42) are key regulators of smooth muscle functions and we recently demonstrated that Rac1 is activated in aSMC from allergic mice. The objective of this study was to assess the role of Rac1 in severe asthma-associated airway remodelling. METHODS AND RESULTS: Immunofluorescence analysis in human bronchial biopsies revealed an increased Rac1 activity in aSMC from patients with severe asthma compared with control subjects. Inhibition of Rac1 by EHT1864 showed that Rac1 signalling controlled human aSMC proliferation induced by mitogenic stimuli through the signal transducer and activator of transcription 3 (STAT3) signalling pathway. In vivo, specific deletion of Rac1 in SMC or pharmacological inhibition of Rac1 by nebulisation of NSC23766 prevented AHR and aSMC hyperplasia in a mouse model of severe asthma. Moreover, the Rac1 inhibitor prevented goblet cell hyperplasia and epithelial cell hypertrophy whereas treatment with corticosteroids had less effect. Nebulisation of NSC23766 also decreased eosinophil accumulation in the bronchoalveolar lavage of asthmatic mice. CONCLUSION: This study demonstrates that Rac1 is overactive in the airways of patients with severe asthma and is essential for aSMC proliferation. It also provides evidence that Rac1 is causally involved in AHR and airway remodelling. Rac1 may represent as an interesting target for treating both AHR and airway remodelling of patients with severe asthma.
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Remodelación de las Vías Aéreas (Respiratorias) , Asma/metabolismo , Miocitos del Músculo Liso/metabolismo , Hipersensibilidad Respiratoria , Proteína de Unión al GTP rac1/metabolismo , Corticoesteroides/farmacología , Aminoquinolinas/administración & dosificación , Aminoquinolinas/farmacología , Animales , Biopsia , Líquido del Lavado Bronquioalveolar/citología , Estudios de Casos y Controles , Proliferación Celular , Modelos Animales de Enfermedad , Eosinófilos/metabolismo , Células Caliciformes/metabolismo , Humanos , Ratones , Pirimidinas/administración & dosificación , Pirimidinas/farmacología , Factor de Transcripción STAT3/metabolismo , Transducción de SeñalRESUMEN
BACKGROUND: Inhaled (ICS) and oral (OCS) corticosteroids are used widely in asthma; however, the risk of osteoporosis and fragility fracture (FF) due to corticosteroids in asthma is not well-established. METHODS: We conducted two nested case-control studies using linked data from the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) databases. Using an asthma cohort, we separately identified patients with osteoporosis or FF and gender-, age- and practice-matched controls. Conditional logistic regression was used to determine the association between ICS and OCS exposure, and the risk of osteoporosis or FF. The prevalence of patients receiving at least one bisphosphonate was also calculated. RESULTS: There was a dose-response relationship between both cumulative dose and number of OCS/ICS prescriptions within the previous year, and risk of osteoporosis or FF. After adjusting for confounders, people receiving more OCS prescriptions (≥9 vs 0) had a 4.50 (95% CI 3.21 to 6.11) and 2.16 (95% CI 1.56 to 3.32) increased risk of osteoporosis and FF, respectively. For ICS (≥11 vs 0) the ORs were 1.60 (95% CI 1.22 to 2.10) and 1.31 (95% CI 1.02 to 1.68). The cumulative dose had a similar impact, with those receiving more OCS or ICS being at greater risk. The prevalence of patients taking ≥9 OCS and at least one bisphosphonate prescription was just 50.6% and 48.4% for osteoporosis and FF, respectively. CONCLUSIONS: The findings suggest that exposure to OCS or ICS is an independent risk factors for bone health in patients with asthma. Steroid administration at the lowest possible level to maintain asthma control is recommended.
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Corticoesteroides/efectos adversos , Asma/tratamiento farmacológico , Fracturas Osteoporóticas/inducido químicamente , Fracturas Osteoporóticas/epidemiología , Administración por Inhalación , Administración Oral , Corticoesteroides/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Osteoporosis/inducido químicamente , Osteoporosis/epidemiología , Fracturas Osteoporóticas/etiología , Factores de Riesgo , Reino Unido/epidemiologíaRESUMEN
Add-on azithromycin (AZM) significantly reduces exacerbations in poorly controlled asthma irrespective of disease phenotype. In a predefined substudy of the original AMAZES protocol (500 mg, three times a week for 48 weeks), we report that AZM treatment reduces key sputum inflammatory proteins (interleukin (IL)-6, IL-1ß and extracellular DNA), which is more evident in non-eosinophilic asthma (NEA). Moreover, AZM reduced Haemophilus influenzae load only in NEA. Our data support the anti-inflammatory effects of AZM in poorly controlled asthma. Prospective studies are required to identify patients that derive greatest benefit from AZM add-on therapy.
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Asma/tratamiento farmacológico , Azitromicina/administración & dosificación , Citocinas/metabolismo , Esputo/metabolismo , Antibacterianos/uso terapéutico , Asma/metabolismo , Humanos , Estudios ProspectivosRESUMEN
BACKGROUND: An as-needed combination preventer and reliever regimen was recently introduced as an alternative to conventional daily preventer treatment for mild asthma. In a subgroup analysis of the PRACTICAL study, a pragmatic randomised controlled trial of budesonide-formoterol reliever therapy versus maintenance budesonide plus terbutaline reliever therapy in adults with mild asthma, we recently reported that about two-thirds preferred as-needed combination preventer and reliever therapy. The aim of this study was to determine the relative importance of attributes associated with these two asthma therapies in this subgroup of participants who indicated their preferred treatment in the PRACTICAL study. METHODS: At their final study visit, a subgroup of participants indicated their preferred treatment and completed a discrete choice experiment using the Potentially All Pairwise RanKings of all possible Alternatives method and 1000minds software. Treatment attributes and their levels were selected from measurable study outcomes, and included: treatment regimen, shortness of breath, steroid dose and likelihood of asthma flare-up. RESULTS: The final analysis dataset included 288 participants, 64% of whom preferred as-needed combination preventer and reliever. Of the attributes, no shortness of breath and lowest risk of asthma flare-up were ranked highest and second highest, respectively. However, the relative importance of the other two attributes varied by preferred therapy: treatment regimen was ranked higher by participants who preferred as-needed treatment than by participants who preferred maintenance treatment. CONCLUSIONS: Knowledge of patient preferences for treatment attributes together with regimen characteristics can be used in shared decision-making regarding choice of treatment for patients with mild-moderate asthma. TRIAL REGISTRATION NUMBER: ACTRN12616000377437.
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Asma/tratamiento farmacológico , Broncodilatadores/uso terapéutico , Combinación Budesonida y Fumarato de Formoterol/uso terapéutico , Participación del Paciente , Prioridad del Paciente , Terbutalina/uso terapéutico , Adulto , Toma de Decisiones Conjunta , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
In the 1990s, metered dose inhalers (MDIs) containing chlorofluorocarbons were replaced with dry-powder inhalers (DPIs) and MDIs containing hydrofluorocarbons (HFCs). While HFCs are not ozone depleting, they are potent greenhouse gases. Annual carbon footprint (CO2e), per patient were 17 kg for Relvar-Ellipta/Ventolin-Accuhaler; and 439 kg for Seretide-Evohaler/Ventolin-Evohaler. In 2017, 70% of all inhalers sold in England were MDI, versus 13% in Sweden. Applying the Swedish DPI and MDI distribution to England would result in an annual reduction of 550 kt CO2e. The lower carbon footprint of DPIs should be considered alongside other factors when choosing inhalation devices.
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Agonistas Adrenérgicos beta/administración & dosificación , Asma/tratamiento farmacológico , Huella de Carbono , Nebulizadores y Vaporizadores , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Administración por Inhalación , Inglaterra , Diseño de Equipo , Fluorocarburos , Humanos , SueciaRESUMEN
BACKGROUND: Allostatic load, a measure of early ageing or 'wear and tear' from adapting to environmental challenges, has been suggested as a framework with which to understand the stress-related disruption of multiple biological systems which may be linked to asthma. Considering the socioeconomic context is also critical given asthma and allostatic overload are more common in lower socioeconomic groups. AIMS: Estimate the relationship between allostatic load and its constituent biomarkers, asthma and corticosteroid prescribing while controlling for socioeconomic status. METHODS: Data from Understanding Society (a nationally representative survey of UK community-dwelling adults) waves 1-3 (2009-2012) allowed the identification of a sex-specific risk profile across 12 biomarkers used to construct an Allostatic Load Index for a sample of 9816 adults. Regression analyses were used to examine the association of asthma status and corticosteroid prescriptions with allostatic load and its constituent biomarkers while controlling for socioeconomic status (n=9805). RESULTS: Subjects with currently treated asthma and no corticosteroid prescription have an allostatic load 1.21 times higher than those without asthma (p<0.001). Asthmatic subjects in receipt of inhaled corticosteroids had an allostatic load, approximately 1.12 times higher than those without asthma (p<0.001). This association persisted in sensitivity analyses and appeared to be driven by an association with specific biomarkers (dehydroepiandrosterone-sulfate, waist-to-height ratio and C-reactive protein). CONCLUSION: Early ageing, in the form of a higher allostatic load, was present even in the mildest asthma group not receiving inhaled corticosteroids. Allostatic load is helpful in understanding the increased all-cause mortality and multimorbidity observed in asthma.
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Corticoesteroides/uso terapéutico , Envejecimiento/fisiología , Alostasis/fisiología , Asma/complicaciones , Asma/metabolismo , Adulto , Anciano , Asma/terapia , Biomarcadores/metabolismo , Proteína C-Reactiva/metabolismo , Estudios Transversales , Sulfato de Deshidroepiandrosterona/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Factores Socioeconómicos , Relación Cintura-EstaturaRESUMEN
BACKGROUND: Respiratory syncytial virus (RSV) is associated with childhood asthma. Nevertheless, not all children exposed to RSV develop asthma symptoms, possibly because genes modulate the effects of RSV on asthma exacerbations. OBJECTIVE: The purpose of this study was to identify genes that modulate the effect of RSV latent infection on asthma exacerbations. METHODS: We performed a meta-analysis to investigate differentially expressed genes (DEGs) of RSV infection from Gene Expression Omnibus datasets. Expression quantitative trait loci (eQTL) methods were applied to select single nucleotide polymorphisms (SNPs) that were associated with DEGs. Gene-based analysis was used to identify SNPs that were significantly associated with asthma exacerbations in the Taiwanese Consortium of Childhood Asthma Study (TCCAS), and validation was attempted in an independent cohort, the Childhood Asthma Management Program (CAMP). Gene-RSV interaction analyses were performed to investigate the association between the interaction of SNPs and RSV latent infection on asthma exacerbations. RESULTS: A total of 352 significant DEGs were found by meta-analysis of RSV-related genes. We used 38 123 SNPs related to DEGs to investigate the genetic main effects on asthma exacerbations. We found that eight RSV-related genes (GADD45A, GYPB, MS4A3, NFE2, RNASE3, EPB41L3, CEACAM6 and CEACAM3) were significantly associated with asthma exacerbations in TCCAS and also validated in CAMP. In TCCAS, rs7251960 (CEACAM3) significantly modulated the effect of RSV latent infection on asthma exacerbations (false-discovery rate <0.05). The rs7251960 variant was associated with CEACAM3 mRNA expression in lung tissue (p for trend=1.2×10-7). CEACAM3 mRNA was reduced in nasal mucosa from subjects with asthma exacerbations in two independent datasets. CONCLUSIONS: rs7251960 is an eQTL for CEACAM3, and CEACAM3 mRNA expression is reduced in subjects experiencing asthma exacerbations. CEACAM3 may be a modulator of RSV latent infection on asthma exacerbations.
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Asma/genética , Asma/virología , Antígeno Carcinoembrionario/genética , ARN Mensajero/metabolismo , Infecciones por Virus Sincitial Respiratorio/complicaciones , Adolescente , Antígenos CD/genética , Asma/fisiopatología , Moléculas de Adhesión Celular/genética , Proteínas de Ciclo Celular/genética , Niño , Progresión de la Enfermedad , Proteína Catiónica del Eosinófilo/genética , Femenino , Proteínas Ligadas a GPI/genética , Perfilación de la Expresión Génica , Genotipo , Glicoforinas/genética , Humanos , Inmunoglobulina M/sangre , Infección Latente/complicaciones , Infección Latente/inmunología , Pulmón/metabolismo , Masculino , Proteínas de la Membrana/genética , Proteínas de Microfilamentos/genética , Subunidad p45 del Factor de Transcripción NF-E2/genética , Polimorfismo de Nucleótido Simple , Mucosa Respiratoria/metabolismo , Infecciones por Virus Sincitial Respiratorio/inmunología , Brote de los SíntomasRESUMEN
Recognition that about half of asthma deaths might be preventable if recommended guidelines are followed suggests that better implementation of established management strategies is needed. However, to achieve a further substantive reduction in asthma mortality, novel strategies will also be required. It is well established that asthma is a disease of chronic inflammation, with episodes of worsening inflammation associated with increased symptoms and/or exacerbations; however, current guidelines paradoxically recommend that initial treatment is only symptomatic, rather than directed at the underlying inflammatory mechanism. The "Treat to target" (TTT) approach has become a popular concept in the medical management of several common chronic conditions, including rheumatoid arthritis (RA), diabetes, hypertension and hyperlipidemia. For example, as part of a TTT approach, rheumatologists recommend methotrexate for RA with onset within 6 months. Applying the TTT approach to asthma, the primary target could be clinical remission and the primary goals as follows: eliminate symptoms and exacerbation risk; prevent airway remodeling; and normalize lung function. To construct a TTT algorithm for chronic asthma, the proposal is to eradicate short-acting ß2-agonists (SABA) at all asthma severity levels and replace SABA with "Anti-Inflammatory Reliever Therapy" (AIR), using inhaled corticosteroids (ICS)/SABA or ICS/formoterol. For individuals with equal to or less than 12 months' history of symptoms, fewer than two symptoms per month, no exacerbations in the last 12 months and normal lung function, the recommendation is early initiation of ICS/SABA or ICS/formoterol as AIR.
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Antiasmáticos/uso terapéutico , Asma/tratamiento farmacológico , Corticoesteroides/uso terapéutico , Agonistas de Receptores Adrenérgicos beta 2/uso terapéutico , Algoritmos , Antiinflamatorios/uso terapéutico , Broncodilatadores/uso terapéutico , Fumarato de Formoterol/uso terapéutico , Humanos , Inducción de Remisión , Índice de Severidad de la EnfermedadRESUMEN
Type-2 biomarkers and related cytokines (IL-5, IL-13), lung function and asthma symptoms were measured in 44 poorly-controlled severe oral corticosteroid (OCS)-dependent asthmatics for up to 88 days after a 7-day prednisolone boost (0.5 mg/kg). High-dose OCS reduced median blood eosinophils (-60 cells/µl; 95% CI -140 to 10), periostin (-8.4 ng/mL; -11.6 to -2.8), FeNO (-19.0 ppb; -28.5 to -4.0), IL-5 (-0.17 pg/mL; -0.28 to -0.08) and IL-13 (-0.15 pg/mL; -0.27 to -0.03). There were small improvements in mean FEV1 (0.16 L; 0.05 to 0.27) and (Asthma Control Questionnaire) ACQ-7 score (0.3; 0.0 to 0.7). Study measures returned to baseline 1-month postintervention. Following rescue OCS, 1 month is sufficient before using type-2 biomarkers to guide long-term treatment. TRIAL REGISTRATION NUMBER: NCT01948401.
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Antiinflamatorios/uso terapéutico , Asma/tratamiento farmacológico , Asma/fisiopatología , Eosinófilos , Interleucina-13/sangre , Interleucina-5/sangre , Prednisolona/uso terapéutico , Administración Oral , Adulto , Antiinflamatorios/administración & dosificación , Asma/sangre , Biomarcadores/sangre , Pruebas Respiratorias , Moléculas de Adhesión Celular/sangre , Femenino , Volumen Espiratorio Forzado , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Óxido Nítrico/análisis , Prednisolona/administración & dosificación , Capacidad VitalAsunto(s)
Asma , Rinitis Alérgica , Inmunoterapia Sublingual , Humanos , Eosinófilos , Asma/terapia , AlérgenosRESUMEN
BACKGROUND: We assessed the efficacy of the licensed mepolizumab dose (100 mg subcutaneously [SC]) in patients with severe eosinophilic asthma according to body weight/body mass index (BMI). METHODS: This was a post hoc individual patient-level meta-analysis of data from the Phase 3 studies MENSA (MEA115588/NCT01691521) and MUSCA (200862/NCT02281318). Patients aged ≥12 years with severe eosinophilic asthma and a history of exacerbations were randomised to 4-weekly placebo, mepolizumab 75 mg intravenously (IV) or 100 mg SC (MENSA) or placebo or mepolizumab 100 mg SC (MUSCA) for 32 (MENSA) or 24 (MUSCA) weeks. The primary endpoint was the annual rate of clinically significant exacerbations; other outcomes included the proportion of patients with no exacerbations, lung function, St George's Respiratory Questionnaire (SGRQ) and Asthma Control Questionnaire-5 (ACQ-5) scores and blood eosinophil counts. Analyses were performed by baseline body weight and BMI (≤60, > 60-75, > 75-90, > 90, < 100, ≥100 kg; ≤25, > 25-30, > 30, < 36, ≥36 kg/m2). RESULTS: Overall, 936 patients received placebo or mepolizumab 100 mg SC. Across all body weight/BMI categories, mepolizumab reduced the rate of clinically significant exacerbations by 49-70% versus placebo. Improvements with mepolizumab versus placebo were also seen in lung function in all body weight/BMI categories except > 90 kg; improvements in SGRQ and ACQ-5 scores were seen across all categories. CONCLUSIONS: Mepolizumab 100 mg SC has consistent clinical benefits in patients with severe eosinophilic asthma across a range of body weights and BMIs. Data show that the fixed-dose regimen of mepolizumab is suitable, without the need for weight-based dosing. TRIAL REGISTRATION: This manuscript is a post hoc meta-analysis of data from the Phase 3 studies MENSA and MUSCA. ClinicalTrials.gov, NCT01691521 (MEA115588; MENSA). Registered September 24, 2012. ClinicalTrials.gov, NCT02281318 (200862; MUSCA). Registered November 3, 2014.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Asma/tratamiento farmacológico , Índice de Masa Corporal , Peso Corporal/efectos de los fármacos , Eosinofilia Pulmonar/tratamiento farmacológico , Índice de Severidad de la Enfermedad , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/farmacología , Asma/diagnóstico , Asma/epidemiología , Peso Corporal/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Eosinofilia Pulmonar/diagnóstico , Eosinofilia Pulmonar/epidemiologíaRESUMEN
Efficacy of omalizumab in severe asthma is well documented; however, the optimal duration of the treatment remains unclear. In an open prospective study, we sought to assess the persistence of response in subjects withdrawing from omalizumab treatment. We evaluated 49 patients who voluntarily accepted to discontinue omalizumab treatment after 6 years of therapy. Asthma relapse was defined as any severe asthma exacerbation associated with loss of asthma control. Twelve patients relapsed in the first year of follow-up, and 7 within 13 and 48 months. These results suggest that the effects of 6 years of omalizumab may persist after discontinuation of therapy in 60% of patients for at least 4 years.