RESUMO
BACKGROUND: The burden of symptoms and risk of exacerbations are the main drivers of the overall assessment of the Chronic Obstructive Pulmonary Disease (COPD) and the adequate treatment approaches per current Global Initiative for Chronic Obstructive Lung Disease (GOLD). Physical activity has emerged as both functional outcome and non-pharmacological intervention in COPD patients, despite the lack of standardized measures or guidelines in clinical practice. This study aimed to explore in more depth the 24-h respiratory symptoms, the physical activity level (PAL) and the relationship between these two determinants in stable COPD patients. METHODS: This was a multinational, multicenter, observational, cross-sectional study conducted in ten European countries and Israel. Dedicated questionnaires for each part of the day (morning, daytime, night) were used to assess respiratory symptoms. PAL was evaluated with self- and interview-reported tools [EVS (exercise as vital sign) and YPAS (Yale Physical Activity Survey)], and physician's judgement. Patients were stratified in ABCD groups by 2013 and 2017 GOLD editions using the questionnaires currently recommended: modified Medical Research Council dyspnea scale and COPD Assessment Test. RESULTS: The study enrolled 2190 patients (mean age: 66.9 years; male: 70.0%; mean % predicted FEV1: 52.6; GOLD groups II-III: 84.5%; any COPD treatment: 98.9%). Most patients (> 90%) reported symptoms in any part of the 24-h day, irrespective of COPD severity. PAL evaluations showed discordant results between patients and physicians: 32.9% of patients considered themselves completely inactive, while physicians judged 11.9% patients as inactive. By YPAS, the overall study population spent an average of 21.0 h/week performing physical activity, and 68.4% of patients were identified as sedentary. In any GOLD ABCD group, the percentage of inactive patients was high. Our study found negative, weak correlations between respiratory symptoms and self-reported PAL (p < 0.001). CONCLUSIONS: Despite regular treatment, the majority of stable COPD patients with moderate to severe disease experienced daily variable symptoms. Physical activity level was low in this COPD cohort, and yet overestimated by physicians. With evidence indicating the negative consequences of inactivity, its adequate screening, a more active promotion and regular assessment of physical activity are urgently needed in COPD patients for better outcomes. TRIAL REGISTRATION: NCT03031769 , retrospectively registered, 23 Jan 2017.
Assuntos
Exercício Físico/fisiologia , Internacionalidade , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Comportamento Sedentário , Autorrelato/normas , Adulto , Idoso , Estudos Transversais , Europa (Continente)/epidemiologia , Feminino , Humanos , Israel/epidemiologia , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/fisiopatologiaRESUMO
OBJECTIVES: The aim of this study was to compare the cytokine levels of subjects with nasal polyps (NP) and comorbid asthma and NP patients without asthma. PATIENTS AND METHODS: Thirty patients with NP (15 asthmatic and 15 nonasthmatic) were included in this prospective study. Nasal secretion samples were collected from the nasal cavities of all subjects. The levels of eleven cytokines (TNF-alpha, TNF-beta, IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, and IFN-gamma) were measured using flow cytometric method. RESULTS: The concentrations of Th2 cytokines IL-5, IL-6 and IL-10 were significantly higher in patients with NP and asthma compared with subjects with NP without asthma. IFN-gamma, IL-4, IL-6 and IL-10 levels were found significantly higher in allergic patients with NP and asthma compared with those without asthma. In nonallergic patients with NP and asthma, the concentrations of TNF-alpha, IL-5 and IL-6 were significantly higher than in nonallergic patients with NP without asthma. CONCLUSION: Our results showed that the presence of Th2 cytokines, especially IL-5 and IL-6 in patients with NP and asthma is a prominent feature that relates to increased eosinophilic inflammation. We also found significant influence of asthma and allergy on the cytokine profiles in nasal secretions of patients with NP.
Assuntos
Asma/fisiopatologia , Citocinas/metabolismo , Hipersensibilidade/fisiopatologia , Pólipos Nasais/fisiopatologia , Adulto , Eosinófilos/metabolismo , Eosinófilos/fisiologia , Feminino , Citometria de Fluxo/métodos , Humanos , Inflamação/fisiopatologia , Interleucina-10/metabolismo , Interleucina-5/metabolismo , Interleucina-6/metabolismo , Masculino , Pessoa de Meia-Idade , Valores de ReferênciaRESUMO
A new palladium(II) complex 1 of the condensation product of 2-(diphenylphosphino)benzaldehyde (dpba) and ethyl hydrazinoacetate (etha) was synthesized and characterized by elemental analyses, IR, and (1)H NMR spectroscopy. The bound ligand is a bidentate (PN chromophore), the remaining two coordination places being occupied by chloride ions in overall square planar geometry. The cytotoxic activity of the complex 1 and two related Pd(II) and Pt(II) complexes 2 and 3 was tested against a panel of four tumor cell lines. The activity of the complexes was similar to that of cisplatin, the most widely used metal-based antitumor drug. It is important to notice that complexes 2 and 3 were active to cisplatin-resistant U2-OS/Pt cells. Cell cycle alteration investigation, apoptotic assay and gelatin zymography in relation to invasion and metastasis of tumor cells, were performed with all the investigated complexes on Human cervix carcinoma (HeLa) cells. The results suggest that 1 has a similar effect to cisplatin, inducing apoptosis followed by arrest of cells in S phase of cell cycle, while 2 and 3 induce apoptosis without significant perturbations of cell cycle distribution.
Assuntos
Benzaldeídos/química , Glicina/análogos & derivados , Paládio/química , Platina/química , Animais , Apoptose/efeitos dos fármacos , Benzaldeídos/síntese química , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Citometria de Fluxo , Gelatina/química , Gelatina/metabolismo , Glicina/síntese química , Glicina/química , Células HeLa , Humanos , Estrutura Molecular , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Compostos Organometálicos/farmacologiaRESUMO
The aim of this study was to compare the cytokine levels in nasal fluid in subjects with nasal polyposis (NP) and co-morbid asthma and NP patients without asthma and to correlate these levels with clinical parameters of severity of disease. Forty NP patients (20 asthmatic and 20 nonasthmatic) were enrolled. Nasal secretion samples were collected from nasal cavities of all 40 subjects. The levels of Th1 cytokines IL-2, IL-12 and IFN-γ, Th2 cytokines IL-4, IL-5, IL-6, and IL-10, chemokine IL-8, and proinflammatory cytokines IL-1ß, TNF-α and TNF-ß were measured using flow cytometric method. Each of the 40 patients was staged clinically according to global nasal symptom score, endoscopic score, and Lund-Mackay computed tomography (CT) score. The concentrations of Th2 cytokines IL-5, IL-6 and IL-10 were significantly higher (P < 0.01, P < 0.01, P < 0.05) in patients with NP and asthma compared with NP patients without asthma. Positive correlations were observed between concentration of IL-2 in nasal secretions and global nasal symptom score, endoscopic score, and Lund-Mackay score only in NP patients without asthma. We also found positive correlation between CT score and the levels of IL-8, IL-4, and IL-1ß in nonasthmatic patients. Finally, our results showed a positive correlation between IL-5 levels in nasal fluid and endoscopic score only in asthmatic patients. NP in asthmatic patients have different immunological patterns compared to those without asthma. We also concluded that concentrations of cytokines measured in nasal fluid were not sensitive enough to determine the severity of disease.
RESUMO
The aim of this prospective study was to evaluate whether cytokine levels in nasal secretions may be clinical parameters of severity of nasal polyposis. Forty nasal polyp patients (20 asthmatic and 20 nonasthmatic) requiring surgical treatment were included. Nasal secretion samples were collected from nasal cavities of all 40 subjects. The levels of T-helper type 1 (Th1) proinflammatory cytokines IL-2, IL-12, IFN-gamma, IL-1beta, TNF-alpha and TNF-beta, Th2 cytokines IL-4, IL-5 and IL-6, antiinflammatory cytokine IL-10 and chemokine IL-8 were measured using flow cytometric method. Each of the 40 patients was staged clinically according to global nasal symptom score, endoscopic score, and Lund-Mackay computed tomography (CT) score. Eosinophils were counted in hematoxylin-eosin stained sections of all nasal polyp samples. The concentrations of Th2 proinflammatory cytokines IL-5 and IL-6 were significantly higher (P < 0.05 and P < 0.01, respectively) in patients with nasal polyposis and asthma compared with nasal polyp patients without asthma. Positive correlations were observed between IL-2 concentration in nasal secretions and nasal symptom score, endoscopic score, and Lund-Mackay score only in nasal polyp patients without asthma. We also found positive correlation between Lund-Mackay score and the levels of IL-8, IL-4, and IL-1beta in nonasthmatic patients. A positive correlation between IL-5 levels in nasal fluid and endoscopic score was found only in asthmatic patients. Eosinophil counts were higher in asthmatic patients' polyps compared with nonasthmatic ones, but without statistical significance. Nasal polyposis in asthmatic patients has different immunological patterns compared to those without asthma. The concentrations of cytokines measured in nasal fluid were not sensitive enough to be universal criteria to determine the severity of all forms of nasal polyposis.