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INTRODUCTION: Physical inactivity is common in asthma and is recognised as an important modifiable risk for poor clinical outcomes such as impaired asthma control and health-related quality of life (HRQoL). Despite evidence supporting the role of physical activity in reducing the risk of these outcomes, little is known about optimal interventions for increasing physical activity in those with severe disease. This systematic review and meta-analysis evaluates the effectiveness of interventions in increasing physical activity in severe asthma. METHODS: MEDLINE, the Cumulative Index to Nursing and Allied Health Literature, Embase, PubMed, Informit, SPORTDiscus and Cochrane databases were searched up to September 2021 for physical activity-based intervention studies that assessed physical activity outcomes (e.g. steps per day, time spent undertaking physical activity) in adults with severe asthma. Data on asthma-related (e.g. asthma control) and health-related outcomes (e.g. HRQoL) were assessed as secondary outcomes. The revised Cochrane Risk of Bias tool was used to assess risk of bias. Random-effects meta-analyses synthesised data where possible. RESULTS: Four randomised controlled trials (all 12â weeks in duration) including 176 adults with moderate-to-severe asthma were included. An increase in physical activity was reported with a moderate-vigorous intensity aerobic and resistance training intervention (steps per day and time spent undertaking physical activity), and an unsupervised pedometer-based intervention (steps per day). Meta-analyses showed that physical activity interventions had an overall positive effect on steps per day (mean difference (MD) 1588, 95% CI 399-2778; p=0.009, I2=23), asthma control (MD -0.65, 95% CI -0.95--0.35; p<0.0001, I2=0%) and HRQoL (MD 0.56, 95% CI 0.10-1.01; p=0.02, I2=16%) compared to control. CONCLUSION: While there is some evidence supporting the effectiveness of interventions in improving physical activity in adults with severe asthma, higher-quality, large-scale studies of longer duration are needed to determine the optimal intervention.
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Asma , Qualidade de Vida , Adulto , Humanos , Exercício Físico , Comportamento Sedentário , Asma/terapia , ActigrafiaRESUMO
BACKGROUND: Anxiety and depression are comorbidities of severe asthma. However, clinical characteristics associated with coexisting severe asthma and anxiety/depression are poorly understood. The study objective is to determine clinical characteristics associated with anxiety and depressive symptoms in severe asthma. METHODS: Severe asthma participants (N = 140) underwent a multidimensional assessment. Categorization of symptoms of anxiety and depression were based on HADS scale sub-scores and divided into four groups (< 8 on both subscales; ≥ 8 on one subscale; ≥ 8 on both subscales). Clinical characteristics were compared between subgroups. Multivariate logistic regression determined associations of clinical characteristics and anxiety and/or depressive symptoms in people with severe asthma. RESULTS: Participants were (mean ± SD) 59.3 ± 14.7 years old, and 62% female. There were 74 (53%) severe asthma participants without symptoms of anxiety/depression, 11 (7%) with symptoms of anxiety, 37 (26%) with symptoms of depression and 18 (13%) with symptoms of anxiety and depression. Quality of life impairment was greater in participants with symptoms of depression (4.4 ± 1.2) and combined symptoms of anxiety and depression (4.4 ± 1.1). Asthma control was worse in those with symptoms of depression (2.9 ± 1.1) and combined anxiety and depression (2.6 ± 1.0). In multivariate models, dysfunctional breathing was associated with symptoms of anxiety (OR = 1.24 [1.01, 1.53]). Dyspnoea was associated with symptoms of depression (OR = 1.90 [1.10, 3.25]). Dysfunctional breathing (OR 1.16 [1.04, 1.23]) and obesity (OR 1.17 [1.00, 1.35]) were associated with combined symptoms of anxiety and depression. CONCLUSION: People with severe asthma and anxiety and/or depressive symptoms have poorer QoL and asthma control. Dyspnoea, dysfunctional breathing and obesity are associated with these symptoms. These key clinical characteristics should be targeted in severe asthma management.
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Asma , Qualidade de Vida , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Masculino , Ansiedade/diagnóstico , Ansiedade/epidemiologia , Depressão/diagnóstico , Depressão/epidemiologia , Asma/diagnóstico , Asma/epidemiologia , Asma/complicações , Dispneia/diagnóstico , Dispneia/epidemiologia , Obesidade/diagnóstico , Obesidade/epidemiologia , Obesidade/complicaçõesRESUMO
BACKGROUND AND OBJECTIVE: Exercise capacity is associated with health-related quality of life and symptom control in severe asthma. Thus, interventions targeting exercise capacity are likely to be beneficial. However, clinical and biological factors impacting exercise capacity in severe asthma are sparsely investigated. We aimed to describe the association of selected clinical and biological factors with 6-min walk distance (6MWD) in adults with severe asthma and investigate the impact of sex on these outcomes. METHODS: A cross-sectional study in adults with severe asthma was conducted. Exercise capacity was measured by 6-min walk test, and association between 6MWD and predictors were evaluated using multiple linear regression. RESULTS: A total of 137 patients (females, 85; median age, 59 years) were recruited. Overall, asthma control (-15.2 m, 95% CI -22.6 to -7.7; p = 0.0001) and BMI (-3.2 m, 95% CI -5.1 to -1.3; p = 0.001) were significantly associated with exercise capacity (adjusted variance, adj. R2 = 0.425). In females, 5-item Asthma Control Questionnaire (ACQ-5; p = 0.005) and BMI (p < 0.001) were significantly associated with 6MWD (adj. R2 = 0.423). In males, a 0.5-point increase in ACQ-5 was associated with a decrease in 6MWD by 10.2 m (95% CI -22.8 to 2.4; p = 0.11), but no clinical nor biological factors reached statistical significance (adj. R2 = 0.393). CONCLUSION: Asthma symptoms and BMI were associated with exercise capacity in the overall population. Optimizing these factors may enhance the ability of patients to improve their exercise capacity and gain the associated positive health outcomes, but further studies are warranted.
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Asma , Qualidade de Vida , Adulto , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Transversais , Caminhada , Teste de Caminhada , Fatores Biológicos , Teste de Esforço , Tolerância ao ExercícioRESUMO
BACKGROUND AND OBJECTIVE: Caring for people with severe asthma and chronic obstructive pulmonary disease (COPD) can impair the quality of life (QoL) of the carer. We aimed to describe the QoL and needs of severe asthma and COPD carers. METHODS: Carers of severe asthma (n = 89) and COPD (n = 48) completed an online cross-sectional survey assessing QoL and carer support needs using the Short Form Health Survey 12v2 (SF-12), the Hospital Anxiety and Depression Scale (HADS) and Carers Support Needs Assessment Tool (CSNAT) questionnaires. RESULTS: Carers of people with severe asthma and COPD were similar in age (mean ± SD 57.78 ± 14.09 vs. 56.93 ± 12.91) and gender (65% female vs. 66%); however, they differed in caring duration (proportion caring for >10 years: 65% vs. 33%, p < 0.002). QoL was impaired in both groups, but there were no significant differences between severe asthma and COPD carers in either of the SF-12 component scores. The HADS scores revealed no difference between groups. Compared to severe asthma carers, COPD carers had significantly greater needs for: 'having time for self' (33% vs. 13%, p = 0.006), 'equipment to help care for relative' (33% vs. 13%, p = 0.006), 'practical help in the home' (35% vs. 18%, p = 0.006) and 'getting a break from caring overnight' (21% vs. 6%, p = 0.023). CONCLUSION: QoL is impaired in carers of people with severe asthma to a similar degree of COPD carers and other debilitating diseases like cancer. These novel data highlight the support needs of severe asthma carers and identifies areas where tailored support is needed to reduce their substantial carer burden.
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Asma , Doença Pulmonar Obstrutiva Crônica , Cuidadores , Estudos Transversais , Feminino , Humanos , Masculino , Qualidade de VidaRESUMO
RATIONALE: Treatable traits have been proposed as a new paradigm for airway disease management. OBJECTIVES: To characterise treatable traits in a severe asthma population and to determine the efficacy of targeting treatments to these treatable traits in severe asthma. METHODS: Participants (n=140) with severe asthma were recruited to a cross-sectional study and underwent a multidimensional assessment to characterise treatable traits. Eligible participants with severe asthma (n=55) participated in a 16-week parallel-group randomised controlled trial to determine the feasibility and efficacy of management targeted to predefined treatable traits, compared to usual care in a severe asthma clinic. The patient-reported outcome of health-related quality of life was the trial's primary end-point. MAIN RESULTS: Participants with severe asthma had a mean±sd of 10.44±3.03 traits per person, comprising 3.01±1.54 pulmonary and 4.85±1.86 extrapulmonary traits and 2.58±1.31 behavioural/risk factors. Individualised treatment that targeted the traits was feasible and led to significantly improved health-related quality of life (0.86 units, p<0.001) and asthma control (0.73, p=0.01). CONCLUSIONS: Multidimensional assessment enables detection of treatable traits and identifies a significant trait burden in severe asthma. Targeting these treatable traits using a personalised-medicine approach in severe asthma leads to improvements in health-related quality of life, asthma control and reduced primary care acute visits. Treatable traits may be an effective way to address the complexity of severe asthma.
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Asma , Qualidade de Vida , Asma/tratamento farmacológico , Estudos Transversais , Humanos , Pulmão , FenótipoRESUMO
"Treatable traits" have been proposed as a new paradigm for the management of airway diseases, particularly complex disease, which aims to apply personalised medicine to each individual to improve outcomes. Moving new treatment approaches from concepts to practice is challenging, but necessary. In an effort to accelerate progress in research and practice relating to the treatable traits approach, the Treatable Traits Down Under International Workshop was convened in Melbourne, Australia in May 2018. Here, we report the key concepts and research questions that emerged in discussions during the meeting. We propose a programme of research that involves gaining international consensus on candidate traits, recognising the prevalence of traits, and identifying a potential hierarchy of traits based on their clinical impact and responsiveness to treatment. We also reflect on research methods and designs that can generate new knowledge related to efficacy of the treatable traits approach and consider multidisciplinary models of care that may aid its implementation into practice.
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Gerenciamento Clínico , Doenças Respiratórias/complicações , Doenças Respiratórias/terapia , Doença Aguda , Doença Crônica , Progressão da Doença , Feminino , Humanos , Pessoa de Meia-Idade , Fenótipo , Medicina de Precisão , Exacerbação dos SintomasRESUMO
It is largely unrecognised that the impacts of asthma are different in patients with severe disease compared with patients with mild to moderate disease. Severe asthma is associated with a significant health-related quality of life (HRQoL) burden due to excessive symptoms, frequent and life-threatening attacks, increased comorbidity burden, and high pharmacological treatment requirements. Interventions aimed at improving HRQoL need to be specifically tested in populations with severe asthma, including multicomponent interventions targeting the many clinical characteristics associated with the disease. It is necessary to have patient-reported outcome measures developed specifically for severe asthma. Public health messages recognising the significant burden of severe asthma on quality of life are needed.
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Asma/psicologia , Efeitos Psicossociais da Doença , Qualidade de Vida , Antiasmáticos/uso terapêutico , Humanos , Adesão à Medicação/psicologia , Inquéritos e QuestionáriosRESUMO
The management of severe asthma is complex. Multidimensional assessment (MDA) of specific traits has been proposed as an effective strategy to manage severe asthma, although it is supported by few prospective studies. We aimed to systematically review the literature published on MDA in severe asthma, to identify the traits included in MDA and to determine the effect of MDA on asthma-related outcomes. We identified 26 studies and classified these based on study type (cohort/cross-sectional studies; experimental/outcome studies; and severe asthma disease registries). Study type determined the comprehensiveness of the assessment. Assessed traits were classified into three domains (airways, co-morbidities and risk factors). The airway domain had the largest number of traits assessed (mean ± SD = 4.2 ± 1.7) compared with co-morbidities (3.6 ± 2.2) and risk factors (3.9 ± 2.1). Bronchodilator reversibility and airflow limitation were assessed in 92% of studies, whereas airway inflammation was only assessed in 50%. Commonly assessed co-morbidities were psychological dysfunction, sinusitis (both 73%) and gastro-oesophageal reflux disease (GORD; 69%). Atopic and smoking statuses were the most commonly assessed risk factors (85% and 86%, respectively). There were six outcome studies, of which five concluded that MDA is effective at improving asthma-related outcomes. Among these studies, significantly more traits were assessed than treated. MDA studies have assessed a variety of different traits and have shown evidence of improved outcomes. This promising model of care requires more research to inform which traits should be assessed, which traits should be treated and what effect MDA has on patient outcomes.
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Asma/etiologia , Asma/fisiopatologia , Asma/terapia , Broncodilatadores/uso terapêutico , Humanos , Pulmão/fisiopatologia , Fatores de RiscoRESUMO
BACKGROUND: People with asthma may have skeletal muscle dysfunction but data describing core function in severe asthma are limited. OBJECTIVE: To compare core function between people with severe asthma and healthy controls and to determine the difference between males and females. Furthermore, we aimed to investigate the association between core function and breathing symptoms. METHOD: Adults with a diagnosis of severe asthma and healthy controls undertook an assessment that included 3 core function tests: partial sit-up, Biering-Sorensen, and side bridge. Breathing symptoms were assessed by the modified Medical Research Council dyspnea scale, modified Borg scale, and Nijmegen questionnaire. RESULTS: People with severe asthma (n = 136) (38% male, age median [Q1-Q3] 59 y [45-68], body mass index 30 kg/m2 [26-37]) were compared with 66 people without respiratory disease (47% male, age 55 y [34-65], body mass index 25 kg/m2 [22-28]). There was no difference between groups in the partial sit-up (P = .09). However, participants with severe asthma performed worse with the Biering-Sorensen (P < .001), and the left and right side bridge test (P < .001 for both) than the healthy comparison group. Similar results were found when comparing males and females separately. Males with severe asthma had increased function compared with their female counterparts in the left side bridge test. Core function tests correlated with the breathing symptom measures, the modified Medical Research Council, modified Borg scale, and Nijmegen questionnaire (-0.51 > r > -0.19; P ≤ .03). CONCLUSIONS: Adults with severe asthma have worse core function than their control counterparts, independent of sex. Furthermore, as core function decreases, breathing symptoms increase.
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Asma , Índice de Gravidade de Doença , Humanos , Asma/fisiopatologia , Asma/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Inquéritos e Questionários , Dispneia/fisiopatologia , Respiração , Fatores Sexuais , Testes de Função Respiratória , Índice de Massa CorporalRESUMO
BACKGROUND: Asthma and vocal cord dysfunction (VCD), also known as inducible laryngeal obstruction (ILO), may coexist, resulting in worse outcomes for patients. The experience of people with VCD/ILO and coexisting asthma is unknown. OBJECTIVE: We sought to determine whether coexistent VCD/ILO and asthma have deleterious impacts on quality of life. METHODS: We undertook a descriptive qualitative study using one-to-one semistructured interviews with 30 purposively recruited adult participants with a prior confirmed doctor asthma diagnosis and laryngoscopy-confirmed VCD/ILO. A thematic and content analysis was conducted to explore the data. RESULTS: Participants were mostly female (63%), mean ± SD age 63 ± 12 years. Four themes were identified: trapped voice, altered life, knowledge about VCD/ILO, and looking for solutions. Participants reported their voice being trapped in their throat or the voice being suddenly cut off when talking or singing. Self-reported VCD/ILO symptoms including throat tightness and breathlessness were highlighted by participants. The second theme described how patients struggle to communicate or tended to shorten conversations. Insufficient knowledge and existing confusion regarding whether asthma was causing the breathlessness was described in the third theme. Looking for solutions depicted participants' diagnostic journey and how they sought an explanation for the symptoms. CONCLUSIONS: People with asthma and coexisting VCD/ILO experience a substantial burden affecting the quality of life. These data describe the impact on patients with coexisting conditions and should be used to increase clinician awareness of the experience of VCD/ILO from patients' perspectives to support a personalized approach to care.
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Asma , Qualidade de Vida , Disfunção da Prega Vocal , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Disfunção da Prega Vocal/diagnóstico , Idoso , Adulto , Obstrução das Vias Respiratórias , Prega Vocal/fisiopatologiaRESUMO
Introduction: Physical capacity is an important determinant of physical activity in people with obstructive airway disease (OAD). This study aimed to extend the "can do, do do" concept in people with OAD, to identify if people categorised into quadrants based on physical capacity and activity differ by clinical and movement behaviour characteristics. Methods: A total of 281 participants (bronchiectasis n=60, severe asthma n=93, COPD n=70 and control n=58) completed assessments to characterise physical capacity as "can do" versus "can't do" (6-min walk distance < or ≥70% pred) and physical activity as "do do" versus "don't do" (accelerometer-derived moderate to vigorous intensity physical activity (MVPA) < or ≥150â min·week-1). Results: The control group had a greater proportion of people in the "can do, do do" quadrant compared with the OAD groups (76% versus 10-33%). People with OAD in the "can't do, don't do" quadrant had worse clinical characteristics (airflow limitation, comorbidities, quality of life and functional dyspnoea) and spent less time doing light-intensity physical activity (LPA) and more time being sedentary compared with the "can do, do do" quadrant. Discussion: This study highlights that many people with OAD may be inactive because they do not have the physical capacity to participate in MVPA, which is further impacted by greater disease severity. It is important to consider the potential benefits of addressing LPA and sedentary behaviour due to suboptimal levels of these movement behaviours across different quadrants. Future research is needed to investigate if tailoring intervention approaches based on quadrant allocation is effective in people with OAD.
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Background: Disabling symptoms of asthma including breathlessness, cough, wheeze and chest tightness largely impact quality of life; however, how these symptoms impact people with asthma of different severity levels remains unknown. This study aimed to compare and characterise patients' symptom experience and the burden caused, their quality of life, and the medication preferences of people with severe asthma against those of people with mild-to-moderate asthma. Methods: This was a multisite qualitative study involving two focus groups and semistructured interviews of adults with severe asthma undertaken in Australia and UK. Interviews were also undertaken in people with mild-to-moderate asthma. Audio recordings were transcribed and analysed thematically. Results: Participants in both severe asthma and mild-to-moderate asthma groups had a mean±sd age of 57±12â years. Between the severe asthma and mild-to-moderate asthma groups, 62% of participants were female and 86% lived with family. Themes were identified: 1) what is asthma and most bothersome symptoms: both groups reported breathlessness as the most bothersome symptom; 2) impacts on life: disease-related impact differed as people with severe asthma reported significant burden in their quality of life, which encompassed emotional, physical, social and financial wellbeing; and 3) personalised and responsive care: severe asthma interviewees preferred injectable biological therapy as a mode of treatment administration. Conclusions: People with asthma are burdened by breathlessness and cough and other disabling symptoms resulting in impaired quality of life. Understanding the experiences of people with asthma of different severities can improve the patient-clinician partnership.
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BACKGROUND: Breathlessness is a disabling symptom, with complexity that is often under-recognized and undertreated in asthma. OBJECTIVE: To highlight the burden of breathlessness in people with severe compared with mild-to-moderate asthma and identify psychophysiological correlates of breathlessness. METHODS: This was a cross-sectional study of people with mild-to-severe asthma, who attended 2 in-person visits to complete a multidimensional assessment. The proportion of people with mild-to-moderate versus severe asthma who reported physically limiting breathlessness (modified Medical Research Council [mMRC] dyspnea score ≥2) was compared. Psychophysiological factors associated with breathlessness in people with asthma were identified via a directed acyclic graph and explored with multivariate logistic regression to predict breathlessness. RESULTS: A total of 144 participants were included, of whom, 74 (51%) had mild-to-moderate asthma and 70 (49%) severe asthma. Participants were predominantly female (n = 103, 72%) with a median (quartile 1, quartile 3) age of 63.4 (50.5, 69.5) years and body mass index (BMI) of 31.3 (26.2, 36.0) kg/m2. The proportion of people reporting mMRC ≥2 was significantly higher in those with severe- (n = 37, 53%) than those with mild-to-moderate (n = 21, 31%) asthma (P = .013). Dyspnoea-12 Total (8.00 [4.75, 17.00] vs 5.00 [2.00, 11.00], P = .037) score was also significantly higher in the severe asthma group. Significant predictors of physically limiting breathlessness were BMI, asthma control, exercise capacity, and hyperventilation symptoms. Airflow limitation and type 2 inflammation were poor breathlessness predictors. CONCLUSIONS: Over half of people with severe asthma experience physically limiting breathlessness despite treatment. Targeting psychophysiological factors, or traits, associated with breathlessness may help relieve this distressing symptom, which is of high priority to people with asthma.
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Chronic airway diseases including asthma and COPD are prevalent and high-burden conditions with the majority of patients successfully managed in the primary care setting. However, for some patients with more complex disease such as difficult-to-treat or severe asthma, or complex COPD, tertiary care is required. This review provides an overview of the successful tertiary care multidisciplinary respiratory service that operates in Newcastle, New South Wales, Australia, which has been integrated into the tertiary care outpatient clinics for almost three decades. The service is multifaceted in terms of the clinical care it provides; it includes an "Inpatient Service", "Asthma Management Service", "Difficult Airways Clinic", "Drug Administration Clinic", "Rapid Access Clinic" and "Pulmonary Rehabilitation", and has an integrated research programme. The core of the multidisciplinary approach to airway diseases is a person-centred model of care, the "Treatable Traits" approach. The staffing of this service comprises consultant physicians, respiratory advanced trainees, respiratory scientists, physiotherapists, speech pathologists, nurse specialists and a nurse consultant. Patients that present to this service undergo an initial assessment and clinical review by team members, synthesis of relevant data, and development of a diagnosis and management plan. Based on this clinical review, specific interventions are determined according to the traits identified. Over time the service has evolved to accommodate the increasing numbers of patients requiring access to the Difficult Airways Clinic assessment and therapies. This has been facilitated by partnering with the Centres of Excellence in Severe Asthma and Treatable Traits to develop educational and practice management tools.
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BACKGROUND: Whilst multidimensional assessment enables the detection of treatable traits in severe asthma and has the potential to improve patient outcomes, healthcare disparities exist, and little is known about the factors influencing optimal management in severe asthma. This study aimed to explore perceived barriers, and enablers to implementing personalised care in severe asthma, from the healthcare professionals' perspective. METHODS: A descriptive, qualitative study involving a single focus group (n = 7) and semi-structured interviews (n = 33) with multidisciplinary healthcare professionals involved in severe asthma care was conducted. A hybrid thematic and content analysis was undertaken to identify themes, which were then deductively mapped to the Theoretical Domains Framework (TDF). RESULTS: Overall, three emergent themes were identified: (1) Barriers- (2) Enablers- to optimal management; (3) Desired model of care. Across all TDF domains, 6 constructs influenced development and implementation of optimal care: (1) belief about consequences, (2) environmental context and resources, (3) belief about capabilities, (4) social/professional role and identity, (5) goals and (6) knowledge. CONCLUSION: Implementation of personalised care in severe asthma is complex and non-linear. The use of a theory-based approach effectively demonstrated how a variety of behaviours could be targeted to optimise and promote personalised care in different clinical setting.
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Asma , Ciência Translacional Biomédica , Asma/terapia , Pessoal de Saúde , Humanos , Papel Profissional , Pesquisa QualitativaRESUMO
The therapeutic and toxic effects of drugs are often generated through effects on distinct cell types in the body. Selective delivery of drugs to specific cells or cell lineages would, therefore, have major advantages, in particular, the potential to significantly improve the therapeutic window of an agent. Cells of the monocyte-macrophage lineage represent an important target for many therapeutic agents because of their central involvement in a wide range of diseases including inflammation, cancer, atherosclerosis, and diabetes. We have developed a versatile chemistry platform that is designed to enhance the potency and delivery of small-molecule drugs to intracellular molecular targets. One facet of the technology involves the selective delivery of drugs to cells of the monocyte-macrophage lineage, using the intracellular carboxylesterase, human carboxylesterase-1 (hCE-1), which is expressed predominantly in these cells. Here, we demonstrate selective delivery of many types of intracellularly targeted small molecules to monocytes and macrophages by attaching a small esterase-sensitive chemical motif (ESM) that is selectively hydrolyzed within these cells to a charged, pharmacologically active drug. ESM versions of histone deacetylase (HDAC) inhibitors, for example, are extremely potent anticytokine and antiarthritic agents with a wider therapeutic window than conventional HDAC inhibitors. In human blood, effects on monocytes (hCE-1-positive) are seen at concentrations 1000-fold lower than those that affect other cell types (hCE-1-negative). Chemical conjugates of this type, by limiting effects on other cells, could find widespread applicability in the treatment of human diseases where monocyte-macrophages play a key role in disease pathology.
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Sistemas de Liberação de Medicamentos/métodos , Esterases/antagonistas & inibidores , Esterases/química , Macrófagos/efeitos dos fármacos , Monócitos/efeitos dos fármacos , Aminoácidos/química , Animais , Anisomicina/farmacologia , Artrite/imunologia , Carboxilesterase/antagonistas & inibidores , Carboxilesterase/química , Carboxilesterase/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Citocinas/biossíntese , Citocinas/sangue , Citocinas/genética , Inibidores Enzimáticos/farmacologia , Esterases/genética , Ésteres/metabolismo , Proteínas de Choque Térmico HSP90/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Lipopolissacarídeos/farmacologia , Espectroscopia de Ressonância Magnética , Camundongos , Camundongos Transgênicos , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/sangue , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
There is an increasing number of new therapies for severe asthma; however, what outcomes people with severe asthma would like improved and what aspects they prioritise in new medications remain unknown. This study aimed to understand what outcomes are important to patients when prescribed new treatments and to determine the characteristics of importance to patients in their choice of asthma treatments. Participants with severe asthma (n=50) completed a cross-sectional survey that ranked 17 potential hypothetical outcomes of treatment using a seven-point Likert scale, as well as selecting their top five overall outcomes. Participants also completed hypothetical scenarios trading off medication characteristics for four hypothetical add-on asthma treatments. Participants (58% male), had a mean±sd age of 62.2±13.5 years. Their top three prioritised outcomes were: to improve overall quality of life (selected by 83% of people), reduce number and severity of asthma attacks (72.3%), and being able to participate in physical activity (59.6%) When trading off medication characteristics, the majority of patients with severe asthma chose the hypothetical medication with the best treatment efficacy (68%). However, a subgroup of patients prioritised the medication's side-effect profile and mode of delivery to select their preferred medication. People with severe asthma value improved quality of life as an important outcome of treatment. Shared decision-making discussions between clinicians and patients that centre around medication efficacy and side-effect profile can incorporate patient preferences for add-on therapy in severe asthma.
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PURPOSE: Add-on therapies for severe asthma are continually emerging with proven efficacy in randomised controlled trials. To date, however, there are no qualitative studies exploring patients' experiences with these treatments. We aimed to understand the experience of patients who were treated with an add-on therapy for their severe asthma. PATIENTS AND METHODS: A qualitative descriptive study was conducted, participants were recruited from the respiratory clinics and databases of a tertiary referral hospital. Participants with treatment-refractory severe asthma (n=20) prescribed an add-on therapy for >4 months (75% mepolizumab; 25% omalizumab, and 25% macrolide) were recruited. Qualitative semi-structured interviews were conducted, with interviews thematically analysed. RESULTS: Participants' mean (SD) age was 59.5 (15.3) years, and 50% were male. Participants reported 4.5 (2.3) exacerbations in the past year. Asthma Control Questionnaire score was 2.0 (1.4). The monoclonal add-on therapies had been prescribed for a median (IQR) of 12.5 (7.0, 24.0) months. Experience was captured in four emergent themes: "Life is just easier" provided an overall message that the add-on therapy made the participants' life easier in terms of increasing participation, levelling out symptoms, providing more energy and reducing healthcare use. "Prednisone: A necessary evil" was discussed, particularly in terms of dose and dependence and damaging side effects. The theme "worry and hope for the future" referenced treatment non-response or cessation of effect which was discussed by some participants. Finally, "holistic care" was centred on the sentiment that the participant's asthma management and overall health were not related to one aspect or medication alone. CONCLUSION: Patients with severe asthma experience vast improvements in quality-of-life and life participation with add-on therapies, but there remains a significant burden related to oral corticosteroids and incomplete treatment responses. Addressing this residual burden is an important area for future research.
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INTRODUCTION: Family carers and significant others play a fundamental role in the well-being of people with severe asthma. This study aimed to investigate the challenges faced by family carers/significant others of people with severe asthma, to understand if there is an unmet need and to explore coping strategies. METHODS: Carers of people with severe asthma were invited to participate in a face-to-face or telephone interview. Semi-structured interviews were conducted until reaching data saturation of themes. The 20 interviews were recorded and transcribed, and analysis of data followed an inductive thematic approach. RESULTS: We report three overarching emergent themes: 1) "Caring role impacts", which centred around the negative and positive impacts of caring on carers' well-being; 2) "Unmet needs", which encapsulated the support needs participants desired and were categorised into unmet information, biopsychosocial needs and carers' involvement in decision-making; and 3) "Coping strategies", which were central to the range of tools and positive approaches in dealing with caring demands. DISCUSSION: Caring for someone with severe asthma can be burdensome and may negatively affect the physical and psychosocial health of the carer. Various coping strategies are used to manage the demands of these caring roles. Carers of people with severe asthma expressed a need for informational, biopsychosocial and involvement in care decision-making support. Tailored support services that are sensitive to their needs may improve their quality of life and encourage healthcare providers to value and acknowledge the important contribution that carers make.
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PURPOSE: Severe asthma, depression and anxiety often co-exist and increase disease burden. Currently there are no published studies investigating severe asthma and psychological comorbidity using arts-based methodology. We aimed to (i) illustrate the individual experience of adults living with severe asthma, with and without symptoms of depression and/or anxiety and (ii) to explore common characteristics depicted in artworks between those groups. PATIENTS AND METHODS: A qualitative arts-based study was conducted. Adults with severe asthma were categorised into two groups according to Hospital Anxiety and Depression Scale scores (<8 on either subscale [SA-D/A] (N=15) or (≥8 on one or both subscales [SA+D/A] (N=15). Art thematic analysis was undertaken using a hybrid approach. The Common-Sense Model of Self-Regulation was used to examine frequencies in artworks. RESULTS: Participants with severe asthma alone and severe asthma with depression/anxiety were of older age (median 67 and 63 years respectively). There was greater asthma QoL impairment in participants with psychological comorbidity than without (4.7 ± 8.3 versus 5.8 ± 0.85, p=<0.01). Analysis of art works identified three themes: (1) "darkness" depicting misery, isolation and sadness; (2) "impacts" describing physical and social consequences; and (3) "resilience" illustrating acceptance and perseverance of living with all three conditions. CONCLUSION: Art-based research in severe asthma facilitates detailed exploration of intimate and individual experiences. Darkness, impacts and resilience are common themes emerging from artworks. Understanding these experiences may help guide assessment and treatment of psychological comorbidity in the clinic.