RESUMO
BACKGROUND: Tidal expiratory flow limitation (EFLT) is common among COPD patients. Whether EFLT changes during sleep and can be abolished during home ventilation is not known. METHODS: COPD patients considered for noninvasive ventilation used a ventilator which measured within-breath reactance change at 5 Hz (∆Xrs) and adjusted EPAP settings to abolish EFLT. Participants flow limited (∆Xrs > 2.8) when supine underwent polysomnography (PSG) and were offered home ventilation for 2 weeks. The EPAP pressure that abolished EFLT was measured and compared to that during supine wakefulness. Ventilator adherence and subjective patient perceptions were obtained after home use. RESULTS: Of 26 patients with supine EFLT, 15 completed overnight PSG and 10 the home study. In single night and 2-week home studies, EFLT within and between participants was highly variable. This was unrelated to sleep stage or body position with only 14.6% of sleep time spent within 1 cmH2O of the awake screening pressure. Over 2 weeks, mean EPAP was almost half the mean maximum EPAP (11.7 vs 6.4 cmH2O respectively). Group mean ∆Xrs was ≤ 2.8 for 77.3% of their home use with a mean time to abolish new EFLT of 5.91 min. Adherence to the ventilator varied between 71 and 100% in prior NIV users and 36-100% for naïve users with most users rating therapy as comfortable. CONCLUSIONS: Tidal expiratory flow limitation varies significant during sleep in COPD patients. This can be controlled by auto-titrating the amount of EPAP delivered. This approach appears to be practical and well tolerated by patients. TRIAL REGISTRATION: The trial was retrospectively registered at CT.gov NCT04725500.
Assuntos
Expiração/fisiologia , Ventilação não Invasiva/métodos , Polissonografia/métodos , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/terapia , Volume de Ventilação Pulmonar/fisiologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Estudos RetrospectivosRESUMO
BACKGROUND: In 2014 approximately 21,200 patients were diagnosed with oesophageal and gastric cancer in England and Wales, of whom 37 % underwent planned curative treatments. Potentially curative surgical resection is associated with significant morbidity and mortality. For operable locally advanced disease, neoadjuvant chemotherapy (NAC) improves survival over surgery alone. However, NAC carries the risk of toxicity and is associated with a decrease in physical fitness, which may in turn influence subsequent clinical outcome. Lower levels of physical fitness are associated with worse outcome following major surgery in general and Upper Gastrointestinal Surgery (UGI) surgery in particular. Cardiopulmonary exercise testing (CPET) provides an objective assessment of physical fitness. The aim of this study is to test the hypothesis that NAC prior to upper gastrointestinal cancer surgery is associated with a decrease in physical fitness and that the magnitude of the change in physical fitness will predict mortality 1 year following surgery. METHODS: This study is a multi-centre, prospective, blinded, observational cohort study of participants with oesophageal and gastric cancer scheduled for neoadjuvant cancer treatment (chemo- and chemoradiotherapy) and surgery. The primary endpoints are physical fitness (oxygen uptake at lactate threshold measured using CPET) and 1-year mortality following surgery; secondary endpoints include post-operative morbidity (Post-Operative Morbidity Survey (POMS)) 5 days after surgery and patient related quality of life (EQ-5D-5 L). DISCUSSION: The principal benefits of this study, if the underlying hypothesis is correct, will be to facilitate better selection of treatments (e.g. NAC, Surgery) in patients with oesophageal or gastric cancer. It may also be possible to develop new treatments to reduce the effects of neoadjuvant cancer treatment on physical fitness. These results will contribute to the design of a large, multi-centre trial to determine whether an in-hospital exercise-training programme that increases physical fitness leads to improved overall survival. TRIAL REGISTRATION: ClinicalTrials.gov NCT01325883 - 29(th) March 2011.
Assuntos
Quimiorradioterapia Adjuvante/métodos , Quimioterapia Adjuvante/métodos , Procedimentos Cirúrgicos do Sistema Digestório/mortalidade , Neoplasias Gastrointestinais/terapia , Aptidão Física/fisiologia , Inglaterra , Teste de Esforço/métodos , Feminino , Neoplasias Gastrointestinais/mortalidade , Neoplasias Gastrointestinais/fisiopatologia , Humanos , Masculino , Estudos Prospectivos , Qualidade de Vida , Análise de Sobrevida , Resultado do Tratamento , País de GalesRESUMO
Short-acting ß2-agonist bronchodilators are the most common medications used in treating chronic obstructive pulmonary disease (COPD). Genetic variants determining bronchodilator responsiveness (BDR) in COPD have not been identified. We performed a genome-wide association study (GWAS) of BDR in 5789 current or former smokers with COPD in one African-American and four white populations. BDR was defined as the quantitative spirometric response to inhaled ß2-agonists. We combined results in a meta-analysis. In the meta-analysis, single-nucleotide polymorphisms (SNPs) in the genes KCNK1 (P=2.02 × 10(-7)) and KCNJ2 (P=1.79 × 10(-7)) were the top associations with BDR. Among African Americans, SNPs in CDH13 were significantly associated with BDR (P=5.1 × 10(-9)). A nominal association with CDH13 was identified in a gene-based analysis in all subjects. We identified suggestive association with BDR among COPD subjects for variants near two potassium channel genes (KCNK1 and KCNJ2). SNPs in CDH13 were significantly associated with BDR in African Americans.The Pharmacogenomics Journal advance online publication, 27 October 2015; doi:10.1038/tpj.2015.65.
Assuntos
Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Broncodilatadores/uso terapêutico , Pulmão/efeitos dos fármacos , Variantes Farmacogenômicos/genética , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/genética , Negro ou Afro-Americano/genética , Idoso , Caderinas/genética , Europa (Continente) , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Nova Zelândia , América do Norte , Testes Farmacogenômicos , Fenótipo , Canais de Potássio Corretores do Fluxo de Internalização/genética , Canais de Potássio de Domínios Poros em Tandem/genética , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Fatores de Risco , Sarcoglicanas/genética , Índice de Gravidade de Doença , Espirometria , Resultado do Tratamento , População Branca/genéticaRESUMO
The objective of Integrated Care Pathways for Airway Diseases (AIRWAYS-ICPs) is to launch a collaboration to develop multi-sectoral care pathways for chronic respiratory diseases in European countries and regions. AIRWAYS-ICPs has strategic relevance to the European Union Health Strategy and will add value to existing public health knowledge by: 1) proposing a common framework of care pathways for chronic respiratory diseases, which will facilitate comparability and trans-national initiatives; 2) informing cost-effective policy development, strengthening in particular those on smoking and environmental exposure; 3) aiding risk stratification in chronic disease patients, using a common strategy; 4) having a significant impact on the health of citizens in the short term (reduction of morbidity, improvement of education in children and of work in adults) and in the long-term (healthy ageing); 5) proposing a common simulation tool to assist physicians; and 6) ultimately reducing the healthcare burden (emergency visits, avoidable hospitalisations, disability and costs) while improving quality of life. In the longer term, the incidence of disease may be reduced by innovative prevention strategies. AIRWAYSICPs was initiated by Area 5 of the Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing. All stakeholders are involved (health and social care, patients, and policy makers).
Assuntos
Transtornos Respiratórios/terapia , Envelhecimento , Asma/terapia , Tomada de Decisões , Europa (Continente) , União Europeia , Guias como Assunto , Humanos , Cooperação Internacional , Área Carente de Assistência Médica , Doença Pulmonar Obstrutiva Crônica/terapia , Qualidade de Vida , Rinite/terapia , Fatores de Risco , Organização Mundial da SaúdeRESUMO
BACKGROUND: Neoadjuvant chemotherapy (NAC) followed by surgery for resectable oesophageal or gastric cancer improves outcome when compared with surgery alone. However NAC has adverse effects. We assess here whether NAC adversely affects physical fitness and whether such an effect is associated with impaired survival following surgery. METHODS: We prospectively studied 116 patients with oesophageal or gastric cancer to assess the effect of NAC on physical fitness, of whom 89 underwent cardiopulmonary exercise testing (CPET) before NAC and proceeded to surgery. 39 patients were tested after all cycles of NAC but prior to surgery. Physical fitness was assessed by measuring oxygen uptake (VO2 in ml kg(-1) min(-1)) at the estimated lactate threshold (θL) and at peak exercise (VO2 peak in ml kg(-1) min(-1)). RESULTS: VO2 at θL and at peak were significantly lower after NAC compared to pre-NAC values: VO2 at θL 14.5 ± 3.8 (baseline) vs. 12.3 ± 3.0 (post-NAC) ml kg(-1) min(-1); p ≤ 0.001; VO2 peak 20.8 ± 6.0 vs. 18.3 ± 5.1 ml kg(-1) min(-1); p ≤ 0.001; absolute VO2 (ml min(-1)) at θL and peak were also lower post-NAC; p ≤ 0.001. Decreased baseline VO2 at θL and peak were associated with increased one year mortality in patients who completed a full course of NAC and had surgery; p = 0.014. CONCLUSION: NAC before cancer surgery significantly reduced physical fitness in the overall cohort. Lower baseline fitness was associated with reduced one-year-survival in patients completing NAC and surgery, but not in patients who did not complete NAC. It is possible that in some patients the harms of NAC may outweigh the benefits. Trials Registry Number: NCT01335555.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Terapia Neoadjuvante , Consumo de Oxigênio , Aptidão Física , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Estudos de Coortes , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/cirurgia , Teste de Esforço , Tolerância ao Exercício , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/cirurgiaRESUMO
OBJECTIVE: This real-life, global study aimed to investigate current views of and clinical practice in the management of COPD and its exacerbations, among clinicians from both the primary and secondary care settings. METHODOLOGY: We devised an online questionnaire about COPD management and invited 13,613 general practitioners (GPs) and respiratory specialists to respond. Participating clinicians, recruited from an established research panel, treated a minimum of 10 (GPs) or 20 (respiratory specialists) patients with COPD per month. Completed responses were collected from 1400 clinicians from 14 countries. RESULTS: A third of GPs and respiratory specialists reported that the main goal of COPD management was to improve patients' quality of life; only 14% of GPs thought that the prevention of exacerbations was a priority. The study showed a strong preference for inhaled corticosteroids in combination with other treatments, rather than as sole therapy, in line with global guidelines. Fewer GPs than respiratory specialists routinely recommended anticholinergics, pulmonary rehabilitation or oxygen therapy. Clinicians reported that 55% (GPs) and 57% (respiratory specialists) of their COPD patients had experienced an exacerbation in the previous 12 months. Although higher than those reported in clinical trials, these rates were lower than patients' own estimates from a corresponding patient survey, even in mild COPD patients (62%; 80% in severe patients). Despite this, 74% of GPs and 67% of respiratory physicians reported satisfaction with therapies to prevent exacerbations. CONCLUSIONS: This global survey revealed that clinicians' main goal when managing COPD was to improve the lives of their patients, and that few viewed reducing exacerbations as a priority. Despite a relatively high level of adherence to treatment recommendations, it appears that clinicians, particularly GPs, underestimate the frequency and impact of exacerbations. These results suggest a need to raise awareness of exacerbations among both GPs and respiratory specialists.
Assuntos
Doença Pulmonar Obstrutiva Crônica/terapia , Comorbidade , Clínicos Gerais , Fidelidade a Diretrizes , Humanos , Guias de Prática Clínica como Assunto , Doença Pulmonar Obstrutiva Crônica/diagnósticoRESUMO
We investigated the impact of season relative to other determinants of chronic obstructive pulmonary disease (COPD) exacerbation frequency in a long-term international study of patients with forced expiratory volume in 1 s (FEV(1)) <60% predicted. COPD exacerbations were defined by worsening symptoms requiring systemic corticosteroids and/or antibiotics (moderate) or hospital admission (severe). Seasonality effect was calculated as the proportion of patients experiencing an exacerbation each month. Exacerbations in the northern and southern regions showed an almost two-fold increase in the winter months. No seasonal pattern occurred in the tropics. Overall, 38% of exacerbations were treated with antibiotics only, 19% with systemic corticosteroids only and 43% with both, while 20% required hospital admission irrespective of the season. Exacerbation frequency was associated with older age, lower body mass index, lower FEV(1) % pred and history of prior exacerbations. Females and patients with worse baseline breathlessness, assessed using the Medical Research Council (MRC) dyspnoea scale, exacerbated more often (rate ratio (RR) for male versus female 0.7, 95% CI 0.7-0.8 (p<0.001); RR for MRC dyspnoea score 3 versus 1 and 2 combined 1.1, 95% CI 1.1-1.2 (p<0.001)). The effect of season was independent of these risk factors. COPD exacerbations and hospitalisations were more frequent in winter.
Assuntos
Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Pneumologia/métodos , Corticosteroides/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Método Duplo-Cego , Feminino , Volume Expiratório Forçado , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Doença Pulmonar Obstrutiva Crônica/terapia , Risco , Estações do Ano , Resultado do TratamentoAssuntos
Pneumologia/educação , Pneumologia/métodos , Currículo , Educação Médica Continuada/organização & administração , Educação de Pós-Graduação em Medicina/organização & administração , Europa (Continente) , Feminino , Humanos , Masculino , Desenvolvimento de Programas , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/terapiaRESUMO
The oral, selective phosphodiesterase type-4 inhibitor roflumilast reduces exacerbations and improves lung function in patients with severe-to-very severe chronic obstructive pulmonary disease (COPD). We investigated the efficacy and safety of roflumilast used concomitantly with long-acting ß(2)-agonists (LABAs) to reduce exacerbations, and the influence of exacerbation history. Pooled data were analysed from two 12-month, placebo-controlled roflumilast (500 µg once daily) studies involving 3,091 patients with severe-to-very severe COPD. Approximately half of patients used concomitant LABAs; 39% used concomitant short-acting muscarinic antagonists (SAMAs); 27% were frequent exacerbators (two or more exacerbations per year). Roflumilast reduced the rate of moderate or severe exacerbations, with LABA (rate ratio (RR) 0.79, 95% CI 0.69-0.91; p=0.001) or without LABA (RR 0.85, 95% CI 0.74-0.99; p=0.039) and prolonged time both to first (p=0.035 with LABA, p=0.300 without LABA) and second (p=0.018 with LABA, p=0.049 without LABA) exacerbations. Frequent exacerbators experienced a reduction in moderate or severe exacerbations (RR 0.78, 95% CI 0.66-0.91; p=0.002). Similarly, roflumilast remained effective with concomitant SAMA. No differences arose in adverse events between these subgroups. Roflumilast may be used to reduce exacerbations and improve dyspnoea and lung function, without increasing adverse events in COPD patients receiving concomitant LABAs.
Assuntos
Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Aminopiridinas/administração & dosagem , Benzamidas/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Corticosteroides/administração & dosagem , Idoso , Broncodilatadores/administração & dosagem , Ciclopropanos/administração & dosagem , Dispneia/metabolismo , Feminino , Humanos , Pulmão/fisiologia , Masculino , Pessoa de Meia-Idade , Placebos , Análise de RegressãoRESUMO
BACKGROUND: Household air pollution from burning biomass fuel is increasingly recognised as a major global health concern. Biomass smoke is associated with chronic obstructive pulmonary disease (COPD) in Asian and Central American countries, but there are few data from Africa. METHODS: We hypothesised that reported wood smoke as compared to charcoal smoke exposure would be associated with a reduction in forced expiratory volume in 1 second in Malawian adults. Volunteers from urban and rural locations performed spirometry and completed a questionnaire assessing lifestyle, including smoke exposure and symptoms. RESULTS: In total, 374 adults were recruited; 61% were female; 160 cooked using charcoal and 174 used wood. Individuals who used wood as their main domestic fuel had significantly worse lung function than those who used charcoal. Significant factors associated with impaired lung function in the multivariate model were age, sex, height, wood smoke exposure, poverty, smoking and previous tuberculosis. CONCLUSION: Our data suggest that wood smoke and poverty contribute to reduced lung function in rural Africans and that COPD is common in this population. The use of charcoal in rural populations may be relatively protective, and this idea merits further study. The risk factors for impaired lung function in Malawi are multiple and require more detailed characterisation to plan appropriate health interventions.
Assuntos
Poluição do Ar em Ambientes Fechados/efeitos adversos , Doença Pulmonar Obstrutiva Crônica/etiologia , Fumaça/efeitos adversos , Adulto , Biomassa , Carvão Vegetal , Culinária , Estudos Transversais , Feminino , Volume Expiratório Forçado , Humanos , Malaui/epidemiologia , Masculino , Análise Multivariada , Pobreza , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Testes de Função Respiratória , Fatores de Risco , Saúde da População Rural , Espirometria , Inquéritos e Questionários , Saúde da População Urbana , MadeiraRESUMO
Lack of reproducibility of findings has been a criticism of genetic association studies on complex diseases, such as chronic obstructive pulmonary disease (COPD). We selected 257 polymorphisms of 16 genes with reported or potential relationships to COPD and genotyped these variants in a case-control study that included 953 COPD cases and 956 control subjects. We explored the association of these polymorphisms to three COPD phenotypes: a COPD binary phenotype and two quantitative traits (post-bronchodilator forced expiratory volume in 1 s (FEV1) % predicted and FEV1/forced vital capacity (FVC)). The polymorphisms significantly associated to these phenotypes in this first study were tested in a second, family-based study that included 635 pedigrees with 1,910 individuals. Significant associations to the binary COPD phenotype in both populations were seen for STAT1 (rs13010343) and NFKBIB/SIRT2 (rs2241704) (p<0.05). Single-nucleotide polymorphisms rs17467825 and rs1155563 of the GC gene were significantly associated with FEV1 % predicted and FEV1/FVC, respectively, in both populations (p<0.05). This study has replicated associations to COPD phenotypes in the STAT1, NFKBIB/SIRT2 and GC genes in two independent populations, the associations of the former two genes representing novel findings.
Assuntos
Polimorfismo Genético , Doença Pulmonar Obstrutiva Crônica/genética , Fator de Transcrição STAT1/genética , Sirtuína 2/genética , Proteína de Ligação a Vitamina D/genética , Idoso , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Humanos , Masculino , Pessoa de Meia-Idade , Noruega/epidemiologia , Polimorfismo de Nucleotídeo Único , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Testes de Função Respiratória/estatística & dados numéricos , Fumar/epidemiologiaRESUMO
OBJECTIVES: To evaluate the effect of beclomethasone/formoterol versus budesonide/formoterol (non-inferiority) and versus formoterol (superiority) in patients with severe stable chronic obstructive pulmonary disease (COPD). METHODS: A double-blind, double-dummy, randomised, active-controlled, parallel-group study. After 4 weeks run-in with ipratropium/salbutamol (40/200 µg, three times daily) patients were randomised to receive beclomethasone/formoterol (200/12 µg pressurised metered dose inhaler), budesonide/formoterol (400/12 µg dry powder inhaler) or formoterol (12 µg dry powder inhaler) twice daily for 48 weeks. Co-primary efficacy variables were change from baseline to 48 weeks in pre-dose morning forced expiratory volume in 1 s (FEV(1)) and mean rate of COPD exacerbations. RESULTS: Of 718 patients randomised, 703 (232 beclomethasone/formoterol, 238 budesonide/formoterol, 233 formoterol) were in the ITT analysis. Improvement in pre-dose morning FEV(1) was 0.077 L, 0.080 L and 0.026 L for beclomethasone/formoterol, budesonide/formoterol and formoterol respectively (LS mean from the ANCOVA model). Beclomethasone/formoterol was not inferior to budesonide/formoterol (95% CI of the difference -0.052, 0.048) and superior to formoterol (p = 0.046). The overall rate of COPD exacerbations/patient/year was similar and not statistically significantly different among treatments (beclomethasone/formoterol 0.414, budesonide/formoterol 0.423 and formoterol 0.431). Quality of life and COPD symptoms improved in all groups and use of rescue medication decreased. Safety profiles were as expected and treatments well-tolerated. CONCLUSIONS: Beclomethasone/formoterol (400/24 µg) treatment for 48 weeks improved pulmonary function, reduced symptoms compared to formoterol, was safe and well-tolerated in patients with severe stable COPD. Neither of the long-acting ß2-agonist/inhaled corticosteroid combinations affected the low exacerbation rate seen in this population.
Assuntos
Albuterol/uso terapêutico , Beclometasona/uso terapêutico , Broncodilatadores/uso terapêutico , Etanolaminas/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Volume Expiratório Forçado/fisiologia , Fumarato de Formoterol , Humanos , Masculino , Inaladores Dosimetrados , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Qualidade de VidaAssuntos
Doença Pulmonar Obstrutiva Crônica/diagnóstico , Pesquisa Biomédica/tendências , Broncodilatadores/uso terapêutico , Glucocorticoides/uso terapêutico , Humanos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/etiologia , Pneumologia/tendênciasAssuntos
Broncodilatadores/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Agonistas Adrenérgicos beta/uso terapêutico , Quimioterapia Combinada , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Indanos/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Quinolonas/uso terapêuticoRESUMO
Dyspnoea, usually defined as an uncomfortable awareness of breathing, is one of the most frequent and distressing symptoms experienced by patients with lung disease. Idiopathic hyperventilation (IHV) has unknown aetiology and little is known about the mechanisms that cause the characteristic sustained hypocapnia and chronic dyspnoea. We have shown in IHV and other chronic respiratory disorders that air hunger is the dominant sensation during exercise, while resting breathlessness is characterised by an affective component. The increased drive to breathe in IHV, and indeed dyspnoea in all chronic respiratory disorders, might be better understood if the central mechanisms of dyspnoea were known. The aim of the present study was to characterise the cortical processing of respiratory-related sensory inputs in patients with IHV. Four patients with IHV were studied with ethical approval. Respiratory stimulation was produced using transient occlusion of inspiration (TIO) during spontaneous breathing (delivered in early inspiration with duration c. 300 ms; this is well tolerated) while BOLD fMRI was performed on a 3 Tesla Siemens Trio. TIO was associated with significant activation in sensorimotor and pre-motor cortical areas and the cerebellum, notably the anterior insula, an area previously associated with breathlessness in healthy volunteers. These preliminary observations on the pattern of brain activity in response to respiratory stimulation support the hypothesis that breathlessness in IHV may reflect inappropriate cortical processing of respiratory-related sensory inputs.
Assuntos
Encéfalo/fisiologia , Hiperventilação/fisiopatologia , Respiração , Humanos , Inalação/fisiologia , Imageamento por Ressonância MagnéticaRESUMO
INTRODUCTION: Oral mucolytics are now recommended in some treatment guidelines for the management of chronic obstructive pulmonary disease (COPD). This article reviews the evidence for their use and their possible benefits. SOURCES OF DATA: The review is based upon peer reviewed publications relating to the use of mucolytics in COPD cited in PubMed. AREAS OF AGREEMENT: Much of the published evidence is of somewhat poor quality and many studies include patients with both chronic bronchitis and COPD. Mucolytics reduce exacerbations by up to 0.8 exacerbations per year, but have little additional benefit in those on standard maximum therapy. AREAS OF CONTROVERSY: Data that mucolytics improve symptoms, alter mucus or impact health-related quality of life in COPD patients receiving other standard therapy are unconvincing. In those on little or no other treatment, they may reduce exacerbation rate. GROWING POINTS: The use of mucolytics to treat acute exacerbations is promising. AREAS TIMELY FOR DEVELOPING RESEARCH: Head-to-head trials of mucolytics versus long-acting bronchodilators and/or inhaled corticosteroids are lacking. Even in patients with severe COPD who remain symptomatic despite maximal inhaled therapy the role of mucolytics remains unproven.
Assuntos
Expectorantes/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Administração Oral , Humanos , Resultado do TratamentoRESUMO
The TOwards a Revolution in COPD Health (TORCH) study was a 3-yr multicentre trial of 6,112 patients randomised to salmeterol (Salm), fluticasone propionate (FP), a Salm/FP combination (SFC) or placebo (P). Here the cost-effectiveness of treatments evaluated in the TORCH study is assessed. For four regions, 3-yr all-cause hospitalisation, medication and outpatient care costs were calculated. The sample was restricted to the 21 countries (n = 4,237) in which European quality of life five-dimension (EQ-5D) data were collected in order to estimate the number of quality-adjusted life years (QALYs). Regression models were fitted to survival, study medication cost, other medication cost and EQ-5D data in order to estimate total cost, number of QALYs and cost per QALY, adjusted for missing data and region. SFC had a trial-wide estimate of cost per QALY of 43,600 US dollars (USD) compared with P (95% confidence interval 21,400-123,500 USD). Estimates for Salm versus P (197,000 USD) and FP versus P (78,000 USD) were less favourable. The US estimates were greater than those from other regions; for SFC versus P, the cost per QALY was 77,100 (46,200-241,700) USD compared to 24,200 (15,200-56,100) USD in Western Europe. Compared with P, SFC has a lower incremental cost-effectiveness ratio than either FP or Salm used alone, and is, therefore, preferred to these monotherapies on the grounds of cost-effectiveness.
Assuntos
Corticosteroides/economia , Albuterol/análogos & derivados , Androstadienos/economia , Broncodilatadores/economia , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/economia , Administração por Inalação , Corticosteroides/administração & dosagem , Idoso , Albuterol/administração & dosagem , Albuterol/economia , Androstadienos/administração & dosagem , Broncodilatadores/administração & dosagem , Análise Custo-Benefício , Combinação de Medicamentos , Feminino , Fluticasona , Humanos , Masculino , Pessoa de Meia-Idade , Anos de Vida Ajustados por Qualidade de Vida , Xinafoato de SalmeterolRESUMO
The TORCH (Towards a Revolution in COPD Health) trial has highlighted some important issues in the design and analysis of long term trials in chronic obstructive pulmonary disease. These include collection of off-treatment exacerbation data, analysis of exacerbation rates and the effect of inclusion of patients receiving inhaled corticosteroids (ICS) prior to randomisation. When effective medications are available to patients who withdraw, inclusion of off-treatment data can mask important treatment effects on exacerbation rates. Analysis of on-treatment data avoids this bias but it needs to be combined with careful analysis of withdrawal patterns across treatments. The negative binomial model is currently the best approach to statistical analysis of exacerbation rates, while analysis of time to exacerbation can supplement this approach. In the TORCH trial, exacerbation rates were higher among patients with previous use of ICS compared to those with no prior use on all study treatments. Retrospective subgroup analysis suggests ICS reduced exacerbation rates compared with placebo, regardless of prior use of ICS before entry to the study. Factorial analysis provides an alternative analysis for trials with combinations of treatments, but assumes no interaction between treatments, an assumption which cannot be verified by a significance test. No definitive conclusions can yet be drawn on whether ICS treatment has an effect on mortality.