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2.
Int J Chron Obstruct Pulmon Dis ; 13: 3885-3894, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30568440

RESUMO

BACKGROUND: In COPD disturbed sleep is related to exacerbation frequency, poor quality of life, and early mortality. We developed the Manchester Respiratory-related Sleep Symptoms scale (MaRSS) to assess sleep-time symptoms in COPD. METHODS: Focus groups including COPD and age-matched controls were used to develop an item-list, which was then administered to COPD patients and age-matched controls in a cross-sectional study. Hierarchical and Rasch analysis informed item selection and scale unidimensionality. Construct validity was examined using Pearson's correlation with the Sleep Problems Index, St George's Respiratory Questionnaire (SGRQ), and FACIT-Fatigue scale. MaRSS change scores from baseline (stable) to exacerbation were assessed in a separate sub-study of COPD patients. RESULTS: Thirty-six COPD patients and nine age-matched controls produced an initial 26-item list. The cross-sectional study involved 203 COPD patients (male: 63%, mean age 64.7 years) and 50 age-matched controls (male: 56%, mean age 65.8 years). Eighteen items were removed to develop an eight-item unidimensional scale covering breathlessness, chest tightness, cough, sputum production, lack of sleep, and medication use. MaRSS scores significantly correlated with sleep problems, SGRQ Total, and FACIT-Fatigue (r=0.58-0.62) and demonstrated a good fit to the Rasch model (chi-squared=29.2; P=0.04). In the substudy, MaRSS scores demonstrated a moderate effect size from baseline to exacerbation visit in 27 patients with 32 exacerbation episodes (Cohen's d=0.6). CONCLUSION: The MaRSS is a reliable, valid, and clinically responsive measure of respiratory-related symptoms that disturb sleep. It is simple to use and score, making it suitable for research and clinical practice.


Assuntos
Pulmão/fisiopatologia , Medidas de Resultados Relatados pelo Paciente , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Respiração , Transtornos do Sono-Vigília/diagnóstico , Sono , Idoso , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Psicometria , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Reprodutibilidade dos Testes , Transtornos do Sono-Vigília/etiologia , Transtornos do Sono-Vigília/fisiopatologia
3.
Int J Chron Obstruct Pulmon Dis ; 13: 1279-1288, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29719383

RESUMO

BACKGROUND: The effects of anti-inflammatory drugs in COPD patients may vary between different cell types. The aim of the current study was to assess the anti-inflammatory effects of the corticosteroid budesonide and a p38 MAPK inhibitor (AZD7624) on different cell types obtained from COPD patients and healthy controls. METHODS: Eight healthy smokers, 16 COPD infrequent exacerbators, and 16 frequent COPD exacerbators (≥2 exacerbations in the last year) were recruited for bronchoscopy and blood sampling. The anti-inflammatory effects of budesonide and AZD7624 were assessed on cytokine release from lipopolysaccharide-stimulated alveolar macrophages and peripheral blood mononuclear cells and polyinosinic:polycytidylic acid-stimulated bronchial epithelial cells. RESULTS: The anti-inflammatory effects of budesonide varied greatly within a patient according to the cell type studied. Bronchial epithelial cells showed the lowest sensitivity to budesonide, while peripheral blood mononuclear cells showed the greatest sensitivity. AZD7624 had a greater effect than budesonide on cytokine production from bronchial epithelial cells. Exacerbation frequency did not influence corticosteroid sensitivity. CONCLUSION: We observed variable corticosteroid and p38 MAPK inhibitor anti-inflammatory responses within the same individual depending on the cell type studied. These findings support the use of multiple anti-inflammatory strategies in COPD patients due to differences between cell types.


Assuntos
Corticosteroides/farmacologia , Anti-Inflamatórios/farmacologia , Benzamidas/farmacologia , Budesonida/farmacologia , Células Epiteliais/efeitos dos fármacos , Leucócitos Mononucleares/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Macrófagos Alveolares/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Pirazinas/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Idoso , Estudos de Casos e Controles , Células Cultivadas , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Células Epiteliais/enzimologia , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Leucócitos Mononucleares/enzimologia , Pulmão/enzimologia , Macrófagos Alveolares/enzimologia , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/enzimologia , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
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