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INTRODUCTION: Immunoglobulins play a vital role in host immune response and in the pathogenesis of conditions like asthma. Therapeutic agents such as monoclonal antibodies target specific elements of the asthmatic inflammatory cascade. Decisions to utilize these medications are often based on systemic inflammatory profiling without direct insight into the airway inflammatory profile. We sought to investigate the relationship between immunoglobulin and cytokine profiles in the airway and systemic immune compartments of adult asthmatics. METHODS: Blood sampling and bronchoscopy with bronchoalveolar lavage (BAL) were performed in 76 well-defined adult asthmatics. Antibody and cytokine profiles were measured in both BAL and serum using ELISA and quantibody arrays. RESULTS: There was no relationship between BAL and serum levels of IgE. This is of significance in an asthma population. For some analytes, correlation analysis was significant (P < 0.05) indicating representativeness of our cohort and experimental setup in those cases. Nevertheless, the predictive power (r2) of the BAL-to-serum comparisons was mostly low except for TNF-α (r2 = 0.73) when assuming a simple (linear) relationship. CONCLUSION: This study highlights the importance of sample site when investigating the roles of immunoglobulins and cytokines in disease pathogenesis and suggests that both localized and systemic immune responses are at play. The prescription of asthma monoclonal therapy is generally based on systemic evaluation of cytokine and immunoglobulin levels. Our research suggests that this approach may not fully reflect the pathophysiology of the disease and may provide insight into why some patients respond to these targeted therapies while others do not.
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Asma , Líquido da Lavagem Broncoalveolar , Broncoscopia , Citocinas , Imunoglobulina E , Humanos , Asma/imunologia , Asma/tratamento farmacológico , Asma/sangue , Adulto , Masculino , Feminino , Líquido da Lavagem Broncoalveolar/imunologia , Líquido da Lavagem Broncoalveolar/citologia , Pessoa de Meia-Idade , Citocinas/sangue , Imunoglobulina E/sangue , Adulto Jovem , Imunoglobulinas/sangue , IdosoRESUMO
Objective: Information on the preferences of people with asthma for support in managing a flare-up can inform service design which may facilitate appropriate help-seeking. To date, little is known about support preferences for managing a flare-up. The aim of this study was to develop and pilot a discrete choice experiment (DCE) to elicit the preferences of people with asthma with regards to support in managing a flare-up.Methods: Steps in developing the DCE included identification and selection of attributes and levels of the support services, construction of choice tasks, experimental design, construction of DCE instrument, and pretest (n=16) and pilot (n=38) studies of the DCE instrument. A multinomial logit model was used to examine the strength and direction of the six attributes in the pilot study.Results: Our results indicate that from a patient perspective, having a healthcare professional that listens to their concerns was the most valued attribute of support in asthma flare-up management. The other features of support valued by participants were timely access to consultation, a healthcare professional with knowledge of their patient history, a specialist doctor and face-to-face communication. Having a written action plan was the least valued attribute.Conclusions: Our findings suggest patient preference for a model of support in managing their symptoms which includes timely, face-to-face access to a healthcare professional that knows them and listens to their concerns. The findings of the pilot study need to be verified with a larger sample and using models to account for preference heterogeneity.
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Asma , Humanos , Projetos Piloto , Comportamento de Escolha , Modelos Logísticos , Pessoal de Saúde , Preferência do PacienteRESUMO
Early life dietary patterns and timely maturation of mucosa-associated microbial communities are important factors influencing immune development and for establishing robust immune tolerance networks. Microbial fermentation of dietary components in vivo generates a vast array of molecules, some of which are integral components of the molecular circuitry that regulates immune and metabolic functions. These in turn protect against aberrant inflammatory processes and promote effector immune responses that quickly eliminate pathogens. Multiple studies suggest that changes in dietary habits, altered microbiome composition, and microbial metabolism are associated with asthma risk and disease severity. While it remains unclear whether these microbiome alterations are a cause or consequence of dysregulated immune responses, there is significant potential for using diet in targeted manipulations of the gut microbiome and its metabolic functions in promoting immune health. In this article, we will summarize our knowledge to date on the role of dietary patterns and microbiome activities on immune responses within the airways. Given the malleability of the human microbiome, its integration into the immune system, and its responsiveness to diet, this makes it a highly attractive target for therapeutic and nutritional intervention in children with asthma.
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Asma , Microbioma Gastrointestinal , Microbiota , Criança , Humanos , Asma/etiologia , Dieta , Sistema ImunitárioRESUMO
BACKGROUND: The development of single-use flexible or disposable bronchoscopes (SUFBs) has accelerated in recent years, with the reduced risk of infectious transmission and reduced need for endoscopy staffing particularly advantageous in the COVID-19 pandemic era. OBJECTIVE: The objective of this study was to assess the performance of a novel single-use bronchoscope in an academic quaternary referral centre with on-site interventional pulmonology programme. METHODS: With ethical approval in a quaternary referral centre, we prospectively collected data on sequential bronchoscopy procedures using The Surgical Company Broncoflex© range of SUFBs. Data collected included demographic, procedural, scope performance, user satisfaction, and complication parameters in a tertiary bronchoscopy service. RESULTS: 139 procedures were performed by five pulmonology faculty from January to July 2021. The majority were carried out for infection (45%) and malignancy (32%). Most were performed in the endoscopy suite and 8% were COVID positive or suspected. Most procedures reported the highest score in satisfaction (85%) with technical limitations reported in 15% (predominately related to scope suction or inadequate image quality) reverting to a reusable scope in 2.8 %. CONCLUSION: In our subset of patients in a bronchoscopy unit, SUFBs are safe, and both routine and advanced bronchoscopy procedures can be performed with high satisfaction reported.
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Broncoscopia , COVID-19 , Broncoscópios , Humanos , Pandemias , Encaminhamento e ConsultaRESUMO
Motor neuron disease (MND) is a neurodegenerative disorder which leads to progressive muscle weakness including respiratory muscle decline. The introduction of non-invasive ventilation (NIV) has been shown to improve quality of life, survival and slow the rate of pulmonary function decline. A retrospective chart analysis of patients who attended the MND clinic from 2014 to 2019 at a tertiary-referral, academic, teaching hospital was carried out to evaluate if NIV and greater compliance with NIV was associated with improved survival. 111 patients were included. The mean age at diagnosis was 63.8 years and 61.3% were males. 66.7% of our cohort used NIV and of this 66.7%, 44.1% were compliant. There was a significantly longer survival in those who used NIV (p = 0.002) and in those who used NIV optimally (p = 0.02) when both groups were compared to those who did not use NIV. In the bulbar MND group those who were compliant with NIV survived longer than who those who did not use NIV (p = 0.001). We found a significantly longer survival with the use of NIV, the use of NIV optimally and with use of NIV in those with bulbar onset MND compared to those who did not use NIV.
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Doença dos Neurônios Motores , Ventilação não Invasiva , Insuficiência Respiratória , Estudos de Coortes , Humanos , Masculino , Doença dos Neurônios Motores/terapia , Qualidade de Vida , Insuficiência Respiratória/terapia , Estudos RetrospectivosRESUMO
BACKGROUND: It is suggested that airway fungi, in particular Aspergillus may impinge on clinical phenotype in asthma. Indeed, the term severe asthma with fungal sensitization (SAFS) has been coined. We aimed to ascertain whether the presence of fungi, in particular Aspergillus fumigatus, in the airway correlated with asthma severity and control. Furthermore, we aimed to determine whether traditional markers of Aspergillus sensitization related to the presence of Aspergillus within the airway. METHODS: Sixty-nine patients characterized by asthma severity (GINA) and level of control (ACQ-7) underwent bronchoscopy and bronchoalveolar lavage (BAL). Serum was assessed for A fumigatus-specific IgE and total IgE. Galactomannan and relevant cytokine levels were assessed in serum, plasma and BAL. BAL was analyzed for the presence of A fumigatus. RESULTS: In BAL, fungi were visible by microscopy in 70% and present by qPCR in 86% of patients, while A fumigatus was detectable by qPCR in 46%. Plasma and BAL IL-4, IL-6, IL-10, IL-13 and TNF-α correlated with BAL fungal presence, while plasma IL-17 correlated with BAL fungal presence. Aspergillus positive BAL correlated with increased plasma and BAL IL-6 and BAL IL-13. There was no relationship between fungal airway presence and steroid dose, asthma severity or control. The presence of Aspergillus within the airway did not relate to serum IgE positivity for Aspergillus. CONCLUSIONS: Fungi were present in a large proportion of our asthmatic patients' airways, but their presence was not predicted by traditional markers of sensitization, nor did it appear to be related to measures of disease severity or control.
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Aspergilose Broncopulmonar Alérgica , Asma , Aspergillus fumigatus , Asma/diagnóstico , Líquido da Lavagem Broncoalveolar , Humanos , Imunoglobulina E , Índice de Gravidade de DoençaRESUMO
In severe asthma, poor control could reflect issues of medication adherence or inhaler technique, or that the condition is refractory. This study aimed to determine if an intervention with (bio)feedback on the features of inhaler use would identify refractory asthma and enhance inhaler technique and adherence.Patients with severe uncontrolled asthma were subjected to a stratified-by-site random block design. The intensive education group received repeated training in inhaler use, adherence and disease management. The intervention group received the same intervention, enhanced by (bio)feedback-guided training. The primary outcome was rate of actual inhaler adherence. Secondary outcomes included a pre-defined assessment of clinical outcome. Outcome assessors were blinded to group allocation. Data were analysed on an intention-to-treat and per-protocol basis.The mean rate of adherence during the third month in the (bio)feedback group (n=111) was higher than that in the enhanced education group (intention-to-treat, n=107; 73% versus 63%; 95% CI 2.8%-17.6%; p=0.02). By the end of the study, asthma was either stable or improved in 54 patients (38%); uncontrolled, but poorly adherent in 52 (35%); and uncontrolled, but adherent in 40 (27%).Repeated feedback significantly improved inhaler adherence. After a programme of adherence and inhaler technique assessment, only 40 patients (27%) were refractory and adherent, and might therefore need add-on therapy.
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Asma/tratamento farmacológico , Asma/terapia , Biorretroalimentação Psicológica , Adesão à Medicação , Nebulizadores e Vaporizadores , Administração por Inalação , Adulto , Idoso , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pico do Fluxo Expiratório , Estudos ProspectivosRESUMO
INTRODUCTION: Exhaled nitric oxide is believed be a useful surrogate for airways inflammation while non-adherence with therapy is known to be associated with worsening of asthma control. CASE: We present the case of a 49-year-old female with steroid-dependent asthma and an exacerbation rate of >20/year. She was enrolled in a 3-month-long prospective study using a validated diagnostic inhaler device that provided objective evidence of inhaler compliance. Fractional exhaled nitric oxide (FeNO), peak expiratory flow rates, asthma control questionnaires were measured throughout the study period. Peripheral eosinophil count was obtained prior to the study, during the study, and immediately afterwards. RESULTS: Improvement in compliance at the end of the study led to significant improvements in lung function peak expiratory flow rate (PEFR), and objective scores of asthma. There was an observed improvement in PEFR after 4 weeks, with an associated decrease in FeNO from 92 to 9 ppb that plateaued over the remainder of the study. Her eosinophil count was 0.79 × 109/litre prior to starting in the study, 0.37 × 109/litre after 2 months, and 0.1 × 109/litre at the end of the study. CONCLUSION: We believe that this is the first case study to objectively prove that improvements in compliance can lead to dramatic reductions in the overall inflammatory airway response and in particular that improvements in patient compliance are mirrored by marked reduction in FeNO levels. These changes occurred in tandem with an observed clinical improvement in our patient.
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Asma/tratamento farmacológico , Adesão à Medicação , Óxido Nítrico/análise , Testes Respiratórios , Feminino , Humanos , Pessoa de Meia-Idade , Nebulizadores e Vaporizadores , Pico do Fluxo ExpiratórioRESUMO
Asthma is a chronic respiratory disease whose prevalence is increasing in the western world. Recently research has begun to focus on the role the microbiome plays in asthma pathogenesis in the hope of further understanding this respiratory disorder. Considered sterile until recently, the lungs have revealed themselves to contain a unique microbiota. A shift towards molecular methods for the quantification and sequencing of microbial DNA has revealed that the airways harbour a unique microbiota with apparent, reproducible differences present between healthy and diseased lungs. There is a hope that in classifying the microbial load of the asthmatic airway an insight may be afforded as to the possible role pulmonary microbes may have in propagating an asthmatic airway response. This could potentially pave the way for new therapeutic strategies for the treatment of chronic lung conditions such as asthma.
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Asma/microbiologia , Asma/virologia , Pulmão/microbiologia , Pulmão/virologia , Microbiota , Animais , Asma/epidemiologia , Asma/fisiopatologia , Carga Bacteriana , Interações Hospedeiro-Patógeno , Humanos , Hipótese da Higiene , Mediadores da Inflamação/metabolismo , Pulmão/metabolismo , Pulmão/fisiopatologia , Fatores de Risco , Transdução de Sinais , Carga ViralRESUMO
BACKGROUND: Neutrophils are effector cells recruited to airways in patients with asthma. Migration of neutrophils occurs predominantly through activation of the CXCR1 and CXCR2 receptors by CXC chemokines, including IL-8 and Gro-α. The dual CXCR1/CXCR2 antagonist SCH 527123 has been developed to target neutrophil migration to alleviate airway neutrophilia. This study investigated the effects of SCH 527123 on neutrophil levels within the bone marrow, peripheral blood and airways, and on isolated bone marrow and peripheral blood neutrophil migration from mild allergic asthmatics. METHODS: Thirteen subjects with mild allergic asthma completed a double blind, placebo-controlled, multi-center crossover study and were randomized to daily dosing of 30 mg SCH 527123 and placebo for 8 days. Subjects provided bone marrow, peripheral blood and sputum samples pre-dosing and on the last day of dosing. Neutrophil numbers were quantified in all samples and chemotaxis assays were performed on neutrophils purified from bone marrow and peripheral blood. RESULTS: Neutrophil numbers fell significantly in the peripheral blood and sputum following treatment with SCH 527123 compared to placebo treatment. No change in neutrophil numbers was observed in bone marrow. SCH 527123 reduced IL-8-induced migration of purified peripheral blood neutrophils (p < 0.05), but had limited effects on migration of neutrophils purified from bone marrow. CONCLUSIONS: The results from this study demonstrate that oral administration of the dual CXCR1/CXCR2 antagonist SCH 527123 reduces neutrophil levels in the circulation and airways through inhibition of migration. There were no toxic effects of SCH 527123 on granulocytic progenitor cells in the bone marrow.
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Asma/tratamento farmacológico , Benzamidas/farmacologia , Ciclobutanos/farmacologia , Receptores de Interleucina-8A/antagonistas & inibidores , Receptores de Interleucina-8B/antagonistas & inibidores , Adulto , Asma/fisiopatologia , Benzamidas/efeitos adversos , Movimento Celular/efeitos dos fármacos , Estudos Cross-Over , Ciclobutanos/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Masculino , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Escarro/metabolismo , Adulto JovemRESUMO
The lungs have their own microbiota which seems to be altered in disease processes such as asthma. Viral infection accounts for many asthma exacerbations. Little is known about the lung virome, and the role that viruses play in non-exacerbating asthmatics. We aimed to assess if detection of virus in bronchoscopy samples of asthmatic patients in a non-exacerbating state influences their asthma control and modulates airway cytokine composition. Patients were recruited from a specialist asthma clinic and underwent bronchoscopy with standardised bronchoalveolar lavage (BAL). Viral analysis was performed; cell differential and cytokine levels were measured. Forty-six samples were obtained of which 10.8% demonstrated evidence of airway virus, and 91.3% of patients in the cohort were classed as severe asthmatics. Oral steroid use was significantly higher in severe asthmatic patients with virus detected, and the forced expiratory volume in one second tended to be lower in the virus-detected group. It was also found that BAL interleukin-13 and tumor necrosis factor-α levels were significantly higher in severe asthmatic patients with virus detected. Our results suggest that in severe asthmatics in a non-exacerbating state, the presence of virus resulted in overall poorer asthma control. The pattern of cytokine elevation seen in asthmatic patients with virus detected may provide insight to the pathophysiology involved.
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BACKGROUND: Previous studies showed that the combination of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) corrector and potentiator, lumacaftor-ivacaftor (LUMA-IVA) provides meaningful clinical benefits in patients with cystic fibrosis who are homozygous for the Phe508del CFTR mutation. However, little is known about the effect of LUMA-IVA on Proinflammatory Cytokines (PICs). OBJECTIVES: To investigate the impact of LUMA-IVA CFTR modulation on circulatory and airway cytokines before and after 12 months of LUMA-IVA treatment in a real-world setting. METHODS: We assessed both plasma and sputum PICs, as well as standard clinical outcomes including Forced Expiratory Volume in one second (FEV1) %predicted, Body Mass Index (BMI), sweat chloride and pulmonary exacerbations at baseline and prospectively for one year post commencement of LUMA-IVA in 44 patients with cystic fibrosis aged 16 years and older homozygous for the Phe508del CFTR mutation. RESULTS: Significant reduction in plasma cytokines including interleukin (IL)-8 (p<0.05), tumour necrosis factor (TNF)-α (p<0.001), IL-1ß (p<0.001) levels were observed while plasma IL-6 showed no significant change (p=0.599) post-LUMA-IVA therapy. Significant reduction in sputum IL-6 (p<0.05), IL-8 (p<0.01), IL-1ß (p<0.001) and TNF-α (p<0.001) levels were observed after LUMA-IVA therapy. No significant change was noted in anti-inflammatory cytokine IL-10 levels in both plasma and sputum (p=0.305) and (p=0.585) respectively. Clinically significant improvements in FEV1 %predicted (mean+3.38%, p=0.002), BMI (mean+0.8 kg/m2, p<0.001), sweat chloride (mean -19 mmol/L, p<0.001), as well as reduction in intravenous antibiotics usage (mean -0.73, p<0.001) and hospitalisation (mean -0.38, p=0.002) were observed after initiation of LUMA-IVA therapy. CONCLUSION: This real-world study demonstrates that LUMA-IVA has significant and sustained beneficial effects on both circulatory and airway inflammation. Our findings suggest that LUMA-IVA may improve inflammatory responses, which could potentially contribute to improved standard clinical outcomes.
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Fibrose Cística , Humanos , Adulto , Fibrose Cística/tratamento farmacológico , Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Escarro , Cloretos/uso terapêutico , Interleucina-6/uso terapêuticoRESUMO
The prevalence of mental health disorders is high among people with Cystic Fibrosis. The psychological symptoms in CF are associated with poor adherence, worse treatment outcomes, and greater health utilization/cost. Mental health and neurocognitive Adverse Events (AEs) have been reported with all available Cystic Fibrosis Transmembrane conductance Regulator (CFTR) modulators in small groups of patients. We report our experience with a dose reduction strategy in 10 of our patients on elexacaftor/tezacaftor/ivacaftor (7.9% of total number of patients) who self-reported developing intense anxiety, irritability, sleep disturbance and/or mental slowness after initiation of full dose treatment. Standard dose elexacaftor/tezacaftor/ivacaftor resulted in 14.3 points improvement in mean Percent Predicted Forced Expiratory Volume in 1 s (ppFEV1), and a mean difference in sweat chloride of -39.3 mmol/L. We initially discontinued and/or reduced therapy according to the AEs severity, with a subsequent planned dose escalation every 4-6 weeks guided by sustainability of clinical effectiveness, absence of AEs recurrence, and patients' preferences. Clinical parameters including lung function and sweat chloride were monitored for up to 12 weeks to assess ongoing clinical response to the reduced dose regimen. Dose reduction resulted in resolution of self-reported mental/psychological AEs, without loss of clinical effectiveness (ppFEV1 was 80.7% on standard dose, and 83.4% at 12 weeks on reduced dose; sweat chloride was 33.4 and 34 mmol/L on standard and reduced dose, respectively). Furthermore, in a subgroup of patients who completed 24 weeks of the reduced dose regimen, repeat low dose Computed Tomography imaging showed a significant response when compared to pre-initiation of elexacaftor/tezacaftor/ivacaftor.
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BACKGROUND: The clinical value of using digital tools to assess adherence and lung function in uncontrolled asthma is not known. We aimed to compare treatment decisions guided by digitally acquired data on adherence, inhaler technique, and peak flow with existing methods. METHODS: A 32-week prospective, multicentre, single-blinded, parallel, randomly controlled trial was done in ten severe asthma clinics across Ireland, Northern Ireland, and England. Participants were 18 years or older, had uncontrolled asthma, asthma control test (ACT) score of 19 or less, despite treatment with high-dose inhaled corticosteroids, and had at least one severe exacerbation in the past year despite high-dose inhaled corticosteroids. Patients were randomly assigned in a 1:1 ratio to the active group or the control group, by means of a computer-generated randomisation sequence of permuted blocks of varying sizes (2, 4, and 6) stratified by fractional exhaled nitric oxide (FeNO) concentration and recruitment site. In the control group, participants were masked to their adherence and errors in inhaler technique data. A statistician masked to study allocation did the statistical analysis. After a 1-week run-in period, both groups attended three nurse-led education visits over 8 weeks (day 7, week 4, and week 8) and three physician-led treatment adjustment visits at weeks 8, 20, and 32. In the active group, treatment adjustments during the physician visits were informed by digital data on inhaler adherence, twice daily digital peak expiratory flow (ePEF), patient-reported asthma control, and exacerbation history. Treatment was adjusted in the control group on the basis of pharmacy refill rates (a measure of adherence), asthma control by ACT questionnaire, and history of exacerbations and visual management of inhaler technique. Both groups used a digitally enabled Inhaler Compliance Assessment (INCA) and PEF. The primary outcomes were asthma medication burden measured as proportion of patients who required a net increase in treatment at the end of 32 weeks and adherence rate measured in the last 12 weeks by area under the curve in the intention-to-treat population. The safety analyses included all patients who consented for the trial. The trial is registered with ClinicalTrials.gov, NCT02307669 and is complete. FINDINGS: Between Oct 25, 2015, and Jan 26, 2020, of 425 patients assessed for eligibility, 220 consented to participate in the study, 213 were randomly assigned (n=108 in the active group; n=105 in the control group) and 200 completed the study (n=102 in the active group; n=98 in the control group). In the intention-to-treat analysis at week 32, 14 (14%) active and 31 (32%) control patients had a net increase in treatment compared with baseline (odds ratio [OR] 0·31 [95% CI 0·15-0·64], p=0·0015) and 11 (11%) active and 21 (21%) controls required add-on biological therapy (0·42 [0·19-0·95], p=0·038) adjusted for study site, age, sex, and baseline FeNO. Three (16%) of 19 active and 11 (44%) of 25 control patients increased their medication from fluticasone propionate 500 µg daily to 1000 µg daily (500 µg twice a day; adjusted OR 0·23 [0·06-0·87], p=0·026). 26 (31%) of 83 active and 13 (18%) of 73 controls reduced their medication from fluticasone propionate 1000 µg once daily to 500 µg once daily (adjusted OR 2·43 [1·13-5·20], p=0·022. Week 20-32 actual mean adherence was 64·9% (SD 23·5) in the active group and 55·5% (26·8) in the control group (between-group difference 11·1% [95% CI 4·4-17·9], p=0·0012). A total of 29 serious adverse events were recorded (16 [55%] in the active group, and 13 [45%] in the control group), 11 of which were confirmed as respiratory. None of the adverse events reported were causally linked to the study intervention, to the use of salmeterol-fluticasone inhalers, or the use of the digital PEF or INCA. INTERPRETATION: Evidence-based care informed by digital data led to a modest improvement in medication adherence and a significantly lower treatment burden. FUNDING: Health Research Board of Ireland, Medical Research Council, INTEREG Europe, and an investigator-initiated project grant from GlaxoSmithKline.
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Antiasmáticos , Asma , Humanos , Broncodilatadores/uso terapêutico , Estudos Prospectivos , Resultado do Tratamento , Método Duplo-Cego , Asma/tratamento farmacológico , Fluticasona/uso terapêutico , Nebulizadores e Vaporizadores , Corticosteroides/uso terapêutico , Adesão à Medicação , Pulmão , Antiasmáticos/uso terapêuticoRESUMO
A well-functioning 68 year old gentleman presented to our hospital with a macular rash 2 weeks after starting a course of Ciprofloxacin. There was rapid progression of skin involvement including the mucosa, complicated by pancytopaenia. Toxic Epidermal Necrolysis (TEN) was suspected and the patient was administered intravenous immunoglobulins and granulocyte colony stimulating factor. TEN was confirmed on skin biopsy and a lymphocyte transformation test demonstrated sensitisation to Ciprofloxacin. The patient developed multifocal pulmonary infiltrates with evidence of pulmonary involvement and probable pneumonia after 1 week and was treated with broad spectrum antibiotics. He also became dysphagic and suffered recurrent aspiration pneumonias. Follow up studies revealed fixed airways obstruction and features of bronchiolitis on computed tomography. This case highlights pulmonary involvement which can become a chronic complication of TEN, itself precipitated by the rare drug cause of Ciprofloxacin.
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Introduction: Approximately 3%-10% of asthma patients will remain uncontrolled despite maximum, optimal conventional therapy. Treatment of severe refractory asthma often involves the use of targeted biological therapy. Randomised controlled trials have shown improvements in clinical parameters with these treatments but real-world data is lacking. Methods: The clinical parameters, frequency of exacerbations, number of hospital admissions, asthma control questionnaire score (ACQ), forced expiratory volume in one second (FEV1) and maintenance oral corticosteroid (OCS) dose of twenty asthma patients switched from reslizumab to benralizumab or mepolizumab at 1 year prior and 6 months after switching were compared, with adjustments for time. Results: The mean frequency of exacerbations (0.35 v 0.3) and the mean ACQ were essentially unchanged (1.6 v 1.5) following the switch. The number of hospital admissions was one in the 6 months post switch compared to one in 1-year pre switch. 25% of patients were on maintenance OCS before and after switching but one patient required an increased dose post switch resulting in an increase in the mean maintenance OCS dose (1.6â mg to 2.4â mg). The mean FEV1 was unchanged (80% v 77.9%) six months post switching. Regarding asthma control (n = 19), 47.4% were controlled pre and post switch (ACQ < 1.5), 36.8% remained uncontrolled despite switching, 10.5% improved control while 5.3% disimproved. Conclusion: We present real-world clinical outcomes of asthma patients switched from reslizumab to either benralizumab or mepolizumab without a loss of clinical effectiveness in the majority.
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INTRODUCTION: Interleukin 5 (IL-5) inhibitors are an important therapeutic advance in the management of severe, refractory, eosinophilic asthma. However, their utilisation should be targeted to maximise their benefits. This study used multisite, centralised, national data collected over 18 months to perform an observational integrated, retrospective, cohort study of selection criteria for initiation and continuation of IL-5 inhibitor treatment in Ireland. MATERIALS/PATIENTS AND METHODS: We used data from 230 patients who were given anti-IL-5 monoclonal therapy (reslizumab, mepolizumab or benralizumab) in Ireland between 2018 and 2020. Reimbursement of these drugs in Ireland requires fulfilling eligibility criteria defined by the Acute Hospitals Drugs Management Programme with continued reimbursement requiring ongoing submission of clinical data demonstrating clinical effectiveness. RESULTS: IL-5 inhibitor use for 18 months was associated with a total reduction in asthma-associated hospital admissions of 108 (p=0.036) and in non-hospital exacerbations of 85 in 18 months (p=0.014). Respiratory-associated GP visits were reduced from 637 in 12 months to 89 at 6 months and 210 at 18 months of treatment (p<0.001). Oral corticosteroid requirement was reduced or stopped entirely (p<0.001). Subgroup analysis of one site replicated these results and showed a significant reduction in the Asthma Control Questionnaire Score (p<0.001) CONCLUSIONS: Selected patients continued on IL-5 treatment to 18 months had significantly reduced exacerbations, GP visits, oral corticosteroid use and asthma-associated hospitalisations. These results show that anti-IL-5 therapy, in carefully selected and monitored patients with asthma, results in significant improvements in clinical outcomes in a real-world setting.
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Antiasmáticos , Asma , Eosinofilia , Corticosteroides , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Estudos de Coortes , Eosinofilia/tratamento farmacológico , Humanos , Estudos RetrospectivosAssuntos
Aminofenóis/uso terapêutico , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fibrose Cística/tratamento farmacológico , Quinolonas/uso terapêutico , Adolescente , Cloretos/análise , Fibrose Cística/genética , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Homozigoto , Humanos , Mutação , Suor/químicaRESUMO
BACKGROUND: Treatment with Ivacaftor provides a significant clinical benefit in people with cystic fibrosis (PWCF) with the class III G551D-CFTR mutation. This study determined the effect of CFTR modulation with ivacaftor on the lung microbiota in PWCF. METHODS: Using both extended-culture and culture-independent molecular methods, we analysed the lower airway microbiota of 14 PWCF, prior to commencing ivacaftor treatment and at the last available visit within the following year. We determined total bacterial and Pseudomonas aeruginosa densities by both culture and qPCR, assessed ecological parameters and community structure and compared these with biomarkers of inflammation and clinical outcomes. RESULTS: Significant improvement in FEV1, BMI, sweat chloride and levels of circulating inflammatory biomarkers were observed POST-ivacaftor treatment. Extended-culture demonstrated a higher density of strict anaerobic bacteria (p = 0.024), richness (p = 1.59*10-4) and diversity (p = 0.003) POST-treatment. No significant difference in fold change was observed by qPCR for either total bacterial 16S rRNA copy number or P. aeruginosa density for oprL copy number with treatment. Culture-independent (MiSeq) analysis revealed a significant increase in richness (p = 0.03) and a trend towards increased diversity (p = 0.07). Moreover, improvement in lung function, richness and diversity displayed an inverse correlation with the main markers of inflammation (p < 0.05). CONCLUSIONS: Following treatment with ivacaftor, significant improvements in clinical parameters were seen. Despite modest changes in overall microbial community composition, there was a shift towards a bacterial ecology associated with less severe CF lung disease. Furthermore, a significant correlation was observed between richness and diversity and levels of circulating inflammatory markers.