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29 August 2024: This article published in Early View in error. The article is under embargo and will republish on 16th September 2024.
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Mild and moderate asthma cover a wide range of asthma presentations, phenotypes and symptom burden, and account for the majority of people with asthma worldwide. Mild asthma has been difficult to define because of its heterogeneity and wide spectrum of impact and outcomes, including being associated with severe exacerbations. Assessment of mild-moderate asthma is best made by combining asthma symptom control and exacerbation risk as the principle means by which to determine treatment needs. Incontrovertible evidence and guidelines support treatment initiation with anti-inflammatory medication, completely avoiding reliever-only treatment of mild asthma. Shared decision making with patients and a treatable traits approach will ensure that a holistic approach is taken to maximize patient outcomes. Most importantly, mild asthma should be regarded as a reversible, potentially curable condition, remaining in long-term remission through minimizing triggers and optimizing care.
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Antiasmáticos , Asma , Humanos , Antiasmáticos/uso terapêutico , Asma/diagnóstico , Asma/tratamento farmacológico , Administração por Inalação , Cognição , Carga de SintomasRESUMO
Background: Patients with mild asthma are believed to represent the majority of patients with asthma. Disease-associated risks such as exacerbations, lung function decline, and death have been understudied in this patient population. There have been no prior efforts from major societies to describe research needs in mild asthma. Methods: A multidisciplinary, diverse group of 24 international experts reviewed the literature, identified knowledge gaps, and provided research recommendations relating to mild asthma definition, pathophysiology, and management across all age groups. Research needs were also investigated from a patient perspective, generated in conjunction with patients with asthma, caregivers, and stakeholders. Of note, this project is not a systematic review of the evidence and is not a clinical practice guideline. Results: There are multiple unmet needs in research on mild asthma driven by large knowledge gaps in all areas. Specifically, there is an immediate need for a robust mild asthma definition and an improved understanding of its pathophysiology and management strategies across all age groups. Future research must factor in patient perspectives. Conclusions: Despite significant advances in severe asthma, there remain innumerable research areas requiring urgent attention in mild asthma. An important first step is to determine a better definition that will accurately reflect the heterogeneity and risks noted in this group. This research statement highlights the topics of research that are of the highest priority. Furthermore, it firmly advocates the need for engagement with patient groups and for more support for research in this field.
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Asma , Humanos , Estados Unidos , Asma/diagnóstico , Asma/terapia , Sociedades Médicas , CuidadoresRESUMO
BACKGROUND: COVID-19 accelerated healthcare changes, introducing various telehealth services. Work is needed to determine the suitability of telemedicine in the post-pandemic era. AIMS: To explore perceptions and experiences of telemedicine among patients and providers (clinicians and health administrators) who were involved in telemedicine appointments in hospital outpatient clinics in 2020-2022. DESIGN, SETTING AND PARTICIPANTS: Qualitative study: semi-structured interviews were conducted with 37 participants (16 patients and 21 providers) in various hospital specialist outpatient clinics in a New South Wales local health district. RESULTS: Patients were generally satisfied with telemedicine consultations, especially during COVID restrictions, because of the convenience of accessing care from home and minimising the risk of COVID exposure. However, patients considered that the inability to receive a physical examination was a significant disadvantage of telemedicine. Providers had ambivalent perceptions and expressed concerns about mis- and under-diagnoses because of the inability to conduct physical examinations. They considered telemedicine suitable for review appointments but noted an associated increased workload and stressed the need for sustainable funding models (Medicare items). Both patients and providers recognised the need for education/training and better integration of telemedicine platforms into existing infrastructure to facilitate an optimal hybrid model of care. CONCLUSION: Despite expressing some concerns over its limitations, patients valued telemedicine for its convenience and for meeting their needs during the pandemic. While acknowledging that patients experienced some benefits from telemedicine, clinicians expressed concerns about potential missed diagnoses, uncertain clinical outcomes and lack of administrative and technological infrastructure. The ultimate test of telemedicine will be its impact on clinical outcomes versus longstanding models of in-person care.
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COVID-19 , Telemedicina , Estados Unidos , Humanos , Idoso , Medicare , Assistência Ambulatorial , Ambulatório HospitalarRESUMO
Aboriginal Australians experience a high prevalence of chronic obstructive pulmonary disease (COPD), with high rates of potentially preventable hospitalisations. However, little is known about Aboriginal peoples' experiences of living with COPD and how they navigate health care systems. This study used thematic analysis and Aboriginal methodology to explore Aboriginal peoples' lived experiences of COPD, their health care journey from receiving a diagnosis of COPD to the clinical management, and the impact of COPD on their daily lives. We conducted in-depth semi-structured interviews over a 6-month period with 18 Aboriginal adults diagnosed with COPD from four Aboriginal Community Controlled Health Services (ACCHS) in New South Wales, Australia. Reflexive thematic analysis was employed to ensure rigour. The findings revealed deeply personal and reflective stories shaped by historical, social, and cultural realities of Aboriginal peoples living with COPD. Four themes were identified characterising their experiences. Based on the findings, the following guidance is provided on future COPD care for Aboriginal peoples: Better alignment of existing COPD management with Aboriginal peoples' cultural contexts and perspectives to improve access to culturally safe care; Increased funding for ACCHS to enhance COPD management, such as early detection through case finding and access to ACCHS-led pulmonary rehabilitation; Engaging family members in COPD management and providing culturally centred COPD education that facilitates discussions and builds health literacy and self-management skills; Implementing health promotion initiatives to increase awareness and counteract fear and shame to improve early COPD detection.
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Rationale: Exacerbations of chronic obstructive pulmonary disease (COPD) are an important endpoint in multinational clinical treatment trials, but the observed event rate is often lower than anticipated and appears to vary between countries. Objectives: We investigated whether systematic differences in national exacerbation rates might explain this observed variation. Methods: We reviewed data from three large multicenter international randomized trials conducted over an 18-year period with different designs and clinical severities of COPD, comparing bronchodilator and/or inhaled corticosteroids with bronchodilators alone and/or placebo. Exacerbations were defined by antibiotic and/or oral corticosteroid use (moderate) or need for hospitalization (severe). We calculated crude exacerbation rates in the 30 countries contributing 30 or more patients to at least two trials. We grouped data by exacerbation rate based on their first study contribution. Measurements and Main Results: For the 29,756 patients in 41 countries analyzed, the mean exacerbation rate was two- to threefold different between the highest and lowest tertiles of the recruiting nations. These differences were not explained by demographic features, study protocol, or reported exacerbation history at enrollment. Of the 18 countries contributing to all trials, half of those in the highest and half in the lowest tertiles of exacerbation history remained in these groups across trials. Severe exacerbations showed a different rank order internationally. Conclusions: Countries contributing to COPD trials differ consistently in their reporting of healthcare-defined exacerbations. These differences help explain why large studies have been needed to show differences between treatments that decrease exacerbation risk.
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Broncodilatadores , Doença Pulmonar Obstrutiva Crônica , Corticosteroides/uso terapêutico , Broncodilatadores/uso terapêutico , Progressão da Doença , Hospitalização , Humanos , Estudos Multicêntricos como Assunto , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/epidemiologiaRESUMO
BACKGROUND: Despite the high incidence of chronic obstructive pulmonary disease (COPD) in Aboriginal communities in Australia, Aboriginal Health Workers (AHWs) have limited knowledge about effective management. AIM: To evaluate an online education program, co-designed with AHWs and exercise physiologists (EPs) or physiotherapists (PTs), to increase knowledge about COPD and its management. METHODS: AHWs and EPs from four Aboriginal Community Controlled Health Services (ACCHS) were recruited. An Aboriginal researcher and a physiotherapist experienced in COPD management and pulmonary rehabilitation (PR) delivered seven online education sessions. These sessions used co-design principles and an Aboriginal pedagogy framework '8 Ways of learning', which incorporates Aboriginal protocols and perspectives to realign teaching techniques and strengthen learning outcomes. Topics covered were: How the lungs work; What is COPD; Medications and how to use inhalers and COPD Action Plans; Why exercise is important; Managing breathlessness; Healthy eating; Managing anxiety and depression. After each session, AHWs with support from EPs, co-designed education 'yarning' resources using Aboriginal ways of learning to ensure topics were culturally safe for the local Aboriginal community and practiced delivering this at the following session. At the end of the program participants completed an anonymous online survey (5-point Likert scale) to assess satisfaction, and a semi-structured interview about their experience of the online education. RESULTS: Of the 12 participants, 11 completed the survey (7 AHWs, 4 EPs). Most (90%) participants strongly agreed or agreed that the online sessions increased knowledge and skills they needed to support Aboriginal patients with COPD. All (100%) participants felt: their cultural perspectives and opinions were valued and that they were encouraged to include cultural knowledge. Most (91%) reported that delivering their own co-designed yarning scripts during the online sessions improved their understanding of the topics. Eleven participants completed semi-structured interviews about participating in online education to co-design Aboriginal 'yarning' resources. Themes identified were: revealing the Aboriginal lung health landscape; participating in online learning; structuring the online education sessions; co-designing with the facilitators. CONCLUSIONS: Online education using co-design and 8 Ways of learning was rated highly by AHWs and EPs for improving COPD knowledge and valuing cultural perspectives. The use of co-design principles supported the cultural adaptation of COPD resources for Aboriginal people with COPD. TRIAL REGISTRATION: PROSPERO (registration number: CRD42019111405).
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Serviços de Saúde do Indígena , Pneumopatias , Doença Pulmonar Obstrutiva Crônica , Humanos , Povos Aborígenes Australianos e Ilhéus do Estreito de Torres , Pneumopatias/terapia , Doença Pulmonar Obstrutiva Crônica/terapia , Educação de Pacientes como AssuntoRESUMO
BACKGROUND: Individual case series and cohort studies have reported conflicting results in people with asthma on the vulnerability to and risk of mortality from coronavirus disease 2019 (COVID-19). RESEARCH QUESTION: Are people with asthma at a higher risk of being infected or hospitalised or poorer clinical outcomes from COVID-19? METHODS: A systematic review and meta-analysis based on five main databases including the World Health Organization COVID-19 database between 1 December 2019 and 11 July 2021 on studies with a control (non-asthma) group was conducted. Prevalence and risk ratios were pooled using Sidik-Jonkman random-effects meta-analyses. FINDINGS: 51 studies with an 8.08% (95% CI 6.87-9.30%) pooled prevalence of people with asthma among COVID-19 positive cases. The risk ratios were 0.83 (95% CI 0.73-0.95, p=0.01) for acquiring COVID-19; 1.18 (95% CI 0.98-1.42, p=0.08) for hospitalisation; 1.21 (95% CI 0.97-1.51, p=0.09) for intensive care unit (ICU) admission; 1.06 (95% CI 0.82-1.36, p=0.65) for ventilator use; and 0.94 (95% CI 0.76-1.17, p=0.58) for mortality for people with asthma. Subgroup analyses by continent revealed a significant difference in risk of acquiring COVID-19, ICU admission, ventilator use and death between the continents. INTERPRETATION: The risk of being infected with severe acute respiratory syndrome coronavirus 2 was reduced compared to the non-asthma group. No statistically significant differences in hospitalisation, ICU admission and ventilator use were found between groups. Subgroup analyses showed significant differences in outcomes from COVID-19 between America, Europe and Asia. Additional studies are required to confirm this risk profile, particularly in Africa and South America, where few studies originate.
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Asma , COVID-19 , Asma/epidemiologia , Hospitalização , Humanos , Unidades de Terapia Intensiva , SARS-CoV-2RESUMO
BACKGROUND: Around 10% of adults suffer from clinically significant breathlessness. High quality and actionable patient education materials (PEMs) and patient decision aids (PDAs) have an important role for shared decision making and patient self-management. OBJECTIVE: To systematically assess the effectiveness of patient education materials (PEMs) and patient decision aids (PDAs) on clinical outcomes. Secondly, to assess the quality of PEMs and PDAs for breathlessness that are accessible online. METHODS: A systematic review of PEM or PDA intervention for breathlessness published between 1 January 2010 and November 2020 was conducted. An environmental scan and quality assessment of publicly available PEMs and PDAs was also conducted. RESULTS: Out of 2985 records, five studies were eligible for inclusion in this systematic review. Results of two randomised controlled trials suggest potential effectiveness of PEMs to improve patient reported outcomes and reduce healthcare utilization. In the environmental scan, 88 materials were included. Minimum reading age for most was high (Grade 10) and PEMs scored an average of 87% for understandability and 67% for actionability. Based on the DISCERN tool only 10 were classified as high quality. CONCLUSION: There is a paucity of evidence on the effectiveness of PEMs and PDAs for improvement in breathlessness. There is a need to develop higher quality PEMs for breathlessness.
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Técnicas de Apoio para a Decisão , Educação de Pacientes como Assunto , Dispneia/terapia , HumanosRESUMO
BACKGROUND: Strong evidence exists for the benefits of pulmonary rehabilitation (PR) for people with chronic obstructive pulmonary disease (COPD), however the availability of culturally safe PR for Aboriginal and Torres Strait Islander (Indigenous) Peoples is limited. The study aims to determine whether PR can be implemented within Aboriginal Community Controlled Health Services (ACCHS) to improve outcomes for Indigenous people with COPD. METHODS: Multi-centre cohort study using participatory action research guided by the Knowledge-to-Action Framework. ACCHS supportive of enhancing services for chronic lung disease will be recruited. Aboriginal Health Workers (AHW) and the exercise physiologist (EP) or physiotherapist (PT) within these ACCHS will attend a workshop aimed at increasing knowledge and skills related to management of COPD and the provision of PR. Indigenous people with COPD will be invited to attend an 8-week, twice weekly, supervised PR program. OUTCOMES: AHW, EP/PT knowledge, skills and confidence in the assessment and management of COPD will be measured before and immediately after the BE WELL workshop and at 3, 6 and 12 months using a survey. PR participant measures will be exercise capacity (6-minute walk test (6MWT), health-related quality of life and health status at commencement and completion of an 8-week PR program. Secondary outcomes will include: number, length and cost of hospitalisations for a COPD exacerbation in 12-months prior and 12-months post PR; local contextual factors influencing implementation of PR; specific respiratory services provided by ACCHS to manage COPD prior to project commencement and at project completion. Repeated measures ANOVA will be used to evaluate changes in knowledge and confidence over time of AHWs and EP/PTs. Paired t-tests will be used to evaluate change in patient outcomes from pre- to post-PR. Number of hospital admissions in the 12 months before and after the PR will be compared using unpaired t-tests. DISCUSSION: Pulmonary rehabilitation is an essential component of best-practice management of COPD and is recommended in COPD guidelines. Indigenous peoples have limited access to culturally safe PR programs. This study will evaluate whether PR can be implemented within ACCHS and improve outcomes for Indigenous people with COPD. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12617001337369, Registered 2nd September 2017 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373585&isClinicalTrial=False.
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Serviços de Saúde do Indígena , Doença Pulmonar Obstrutiva Crônica , Austrália , Estudos de Coortes , Gerenciamento Clínico , Humanos , Pulmão , Havaiano Nativo ou Outro Ilhéu do Pacífico , Doença Pulmonar Obstrutiva Crônica/reabilitação , Qualidade de VidaRESUMO
BACKGROUND: The highest burden of chronic obstructive pulmonary disease (COPD) occurs in low- and middle-income countries. Low-cost oral medications, if effective, could enable affordable, accessible COPD treatment. METHODS: In this randomised, three-arm, double-blind, double-dummy, placebo-controlled study conducted in 37 centres in China, symptomatic patients with moderate to very severe COPD were randomised 1:1:1 to placebo twice daily plus placebo once daily, low-dose theophylline 100â mg twice daily plus placebo once daily or low-dose theophylline 100â mg twice daily plus low-dose oral prednisone 5â mg once daily for 48â weeks. The primary end-point was annualised exacerbation rate. RESULTS: 1670 subjects were randomised and 1242 completed the study (1142 with acceptable data at week 48). Subjects (75.7% male) had a mean age of 64.4â years, with mean±sd baseline post-bronchodilator forced expiratory volume in 1â s (FEV1) 1.1±0.4â L (42.2% predicted) and St George's Respiratory Questionnaire (SGRQ) score 45.8±20.1. There were negligible differences between annualised exacerbation rates across the three treatments: 0.89 (95% CI 0.78-1.02) on theophylline plus prednisone, 0.86 (95% CI 0.75-0.99) on theophylline plus placebo and 1.00 (95% CI 0.87-1.14) on placebo. The rate ratio for theophylline plus prednisone versus pooled theophylline plus placebo and placebo was 0.96 (95% CI 0.83-1.12), for theophylline plus placebo versus placebo was 0.87 (95% CI 0.73-1.03; p=0.101) and for theophylline plus prednisone versus placebo was 0.90 (95% CI 0.76-1.06; p=0.201). Secondary outcomes of hospitalisations, FEV1, SGRQ and COPD Assessment Test score showed no statistically significant difference between treatment arms. Serious adverse events other than exacerbations were <2% and did not differ between treatment arms. CONCLUSIONS: Low-dose theophylline alone or in combination with prednisone did not reduce exacerbation rates or clinically important secondary end-points compared with placebo.
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Doença Pulmonar Obstrutiva Crônica , Teofilina , Corticosteroides/uso terapêutico , Broncodilatadores/uso terapêutico , China , Método Duplo-Cego , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Teofilina/farmacologia , Teofilina/uso terapêuticoRESUMO
Add-on azithromycin (AZM) results in a significant reduction in exacerbations among adults with persistent uncontrolled asthma. The aim of this study was to assess the cost-effectiveness of add-on AZM in terms of healthcare and societal costs.The AMAZES trial randomly assigned 420 participants to AZM or placebo. Healthcare use and asthma exacerbations were measured during the treatment period. Healthcare use included all prescribed medicine and healthcare contacts. Costs of antimicrobial resistance (AMR) were estimated based on overall consumption and published estimates of costs. The value of an avoided exacerbation was based on published references. Differences in cost between the two groups were related to differences in exacerbations in a series of net monetary benefit estimates. Societal costs included lost productivity, over the counter medicines, steroid induced morbidity and AMR costs.Add-on AZM resulted in a reduction in healthcare costs (mean (95% CI)) including nights in hospital (AUD 433.70 (AUD 48.59-818.81) or EUR 260.22 (EUR 29.15-491.29)), unplanned healthcare visits (AUD 20.25 (AUD 5.23-35.27) or EUR 12.15 (EUR 3.14-21.16)), antibiotic costs (AUD 14.88 (AUD 7.55-22.21) or EUR 8.93 (EUR 4.53-13.33)) and oral corticosteroid costs (AUD 4.73 (AUD 0.82-8.64) or EUR 2.84 (EUR 0.49-5.18)); all p<0.05. Overall healthcare and societal costs were lower (AUD 77.30 (EUR 46.38) and AUD 256.22 (EUR 153.73) respectively) albeit not statistically significant. The net monetary benefit of add-on AZM was estimated to be AUD 2072.30 (95% CI AUD 1348.55-2805.23) or (EUR 1243.38 (EUR 809.13-1683.14) assuming a willingness to pay per exacerbation avoided of AUD 2651 (EUR 1590.60). Irrespective of the sensitivity analysis applied, the net monetary benefit for total, moderate and severe exacerbations remained positive and significant.Add-on AZM therapy in poorly controlled asthma was a cost-effective therapy. Costs associated with AMR did not influence estimated cost-effectiveness.
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Asma , Azitromicina , Corticosteroides/uso terapêutico , Adulto , Antibacterianos/uso terapêutico , Asma/tratamento farmacológico , Azitromicina/uso terapêutico , Análise Custo-Benefício , HumanosRESUMO
Despite improvements in medications, devices and understanding of the disease, about half of all asthma patients worldwide remain inadequately controlled, suggesting the need for a new approach to asthma management. Poor adherence to prescribed maintenance therapy and over-reliance on SABA reliever medication is a common cause of inadequate control. This article reviews published data from 6- to 12-month, double-blind, RCT and open-label real-world studies involving budesonide/formoterol maintenance and reliever therapy (MART) and relevant comparator approaches to asthma management, and considers how these compare in achieving the treatment goals described in guidelines. The data confirm that patients with asthma treated with budesonide/formoterol MART achieved the same or better asthma symptom control compared with ICS/LABA plus SABA regimens at similar or higher ICS doses, with consistently lower rates of exacerbations and considerably lower annual requirement for oral corticosteroids. These findings have been confirmed across a range of severities of persistent asthma. With the MART approach, maintenance dosing ensures coverage for day-to-day control, and the use of a reliever with anti-inflammatory properties (budesonide/formoterol) provides extra doses of ICS as soon as symptoms prompt the use of reliever, resulting in a 40-50% reduction of exacerbations compared with an ICS-based treatment approach plus as-needed SABA as reliever. As-needed, budesonide/formoterol has also recently been shown to be more effective as a reliever in mild asthma than SABA alone, reducing exacerbations by up to 64% in the SYGMA studies.
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Asma/tratamento farmacológico , Asma/prevenção & controle , Budesonida/uso terapêutico , Ensaios Clínicos como Assunto , Fumarato de Formoterol/uso terapêutico , Quimioterapia de Manutenção , Adulto , Antiasmáticos/uso terapêutico , Broncodilatadores/uso terapêutico , Budesonida/administração & dosagem , Feminino , Humanos , MasculinoAssuntos
Broncodilatadores , Doença Pulmonar Obstrutiva Crônica , Administração por Inalação , Broncodilatadores/uso terapêutico , Combinação de Medicamentos , Humanos , Antagonistas Muscarínicos/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/prevenção & controle , Fumantes , Resultado do TratamentoRESUMO
BACKGROUND: Patients requiring non-invasive ventilation for acute-on-chronic respiratory failure due to chronic obstructive pulmonary disease or heart failure exacerbations may have a poor prognosis underscoring the importance of advance care planning. AIM: We aimed to describe attitudes to, and experiences of, discussing the future among patients recently treated with non-invasive ventilation. DESIGN: Qualitative research using thematic analysis. SETTINGS AND PARTICIPANTS: Tertiary teaching hospital. Patients with acute hypercapnic respiratory failure requiring non-invasive ventilation. RESULTS: Individuals recently treated with non-invasive ventilation describe feeling the future is beyond their control and instead controlled by their illness. Participants often recognised their poor prognosis but avoided discussing some difficult topics. The majority preferred not to undergo cardiopulmonary resuscitation but most had not discussed this with healthcare professionals. When participants voiced concerns about their future health to family members, they were met with polarised responses. Some encountered willingness for further discussion, while others met deflection, deterring further conversation. An overarching narrative of 'Looking through my illness to an uncertain but concerning future' unites these themes. CONCLUSION: This study suggests opportunities and barriers for advance care planning in individuals with chronic disease. Patients' understanding of their prognosis and their attitudes to cardiopulmonary resuscitation suggests an opportunity for advance care planning. Structuring discussions around patients' preferences for care during future exacerbations may foster a sense of control over the future despite illness. The diversity of familial responses to patients' concerns about their future health has implications for advance care planning. These findings have the potential to improve care for patients with respiratory failure and suggest an important ongoing research agenda.
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Planejamento Antecipado de Cuidados , Ventilação não Invasiva , Síndrome do Desconforto Respiratório/psicologia , Idoso , Idoso de 80 Anos ou mais , Atitude Frente a Morte , Reanimação Cardiopulmonar/psicologia , Feminino , Insuficiência Cardíaca/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Preferência do Paciente , Doença Pulmonar Obstrutiva Crônica/complicações , Pesquisa Qualitativa , Síndrome do Desconforto Respiratório/terapiaRESUMO
BACKGROUND: Asthma management may involve a step up in treatment when symptoms are not well controlled. We examined whether budesonide/formoterol maintenance and reliever therapy (MRT) is as effective as higher, fixed-dose budesonide plus as-needed terbutaline in patients requiring step-up from Step 2 treatment (low-dose inhaled corticosteroids), stratified by baseline reliever use. METHODS: A post-hoc analysis utilized data from three clinical trials of 6-12 months' duration. Patients aged ≥12 years with symptomatic asthma uncontrolled despite Step 2 treatment were included. Severe exacerbation rate, lung function and reliever use were analysed, stratified by baseline reliever use (<1, 1-2 and >2 occasions/day). RESULTS: Overall, 1239 patients were included. Reductions in severe exacerbation rate with budesonide/formoterol MRT versus fixed-dose budesonide were similar across baseline reliever use levels, and were statistically significant in patients using 1-2 (42%, p = 0.01) and >2 (39%, p = 0.02) reliever occasions/day, but not <1 reliever occasion/day (35%, p = 0.11). Both treatments significantly increased mean FEV1 from baseline; improvements were significantly greater for budesonide/formoterol MRT in all reliever use groups. Reductions in reliever use from baseline were significantly greater with budesonide/formoterol MRT versus fixed-dose budesonide in patients using 1-2 and >2 reliever occasions/day (-0.33 and -0.74 occasions/day, respectively). CONCLUSIONS: Treatment benefit with budesonide/formoterol MRT versus higher, fixed-dose budesonide plus short-acting ß2-agonist was found in Step 2 patients with relatively low reliever use, supporting the proposal that budesonide/formoterol MRT may be useful when asthma is uncontrolled with low-dose inhaled corticosteroid.