健康指导在稳定期COPD治疗中的作用观察

目的探究健康指导在稳定期COPD治疗中的作用。方法随机选取2010年10月至2013年10月我科收治的126例COPD患者,所取病例分为对照组(63例)、指导组(63例)。对照组予以常规治疗,指导组予以健康指导加常规治疗,对照分析两组患者的治疗效果。结果对照组急性加重频次和并发症的发生率明显高于指导组。结论在稳定期COPD的治疗中予以积极健康指导,可减轻患者症状,减少患者的住院率及并发症发生,延缓肺功能的下降,提高了生活质量,     

Changes in body weight and physical performance after receiving dietary advice in patients with chronic obstructive pulmonary disease (COPD): 1-year follow-up

Nutritional studies in patients with chronic obstructive pulmonary disease (COPD) are often based on oral nutritional supplementation and are of short duration. Our aim was to study the changes in body weight and physical performance in COPD patients after receiving the dietary advice for 1 year. Thirty-six patients with COPD as a primary diagnosis (mean age: 68.5 ± 7.8 years), referred to a pulmonary rehabilitation program were studied. Each patient received dietary advice individually. Body weight had increased significantly by 1.3 kg (p = 0.02) and walking distance by 83.2 m (p = 0.007) after 1 year. There was an increase in mean handgrip strength after 1 year (1.6 kg, p = 0.07). The mean intake of energy and protein expressed as percent of energy and protein requirement had increased after 1 year (15%, p < 0.001, and 5.6%, p = 0.09, respectively). Handgrip strength correlated significantly with energy (r = 0.53, p = 0.002), fat (r = 0.50, p = 0.02) and protein intake (r = 0.41, p = 0.002) after 1 year. In conclusion, positive effects on body weight, handgrip strength and walking distance in patients with COPD were seen after receiving dietary advice with a 1-year follow-up.     

SIRT4 inhibits cigarette smoke extracts-induced mononuclear cell adhesion to human pulmonary microvascular endothelial cells via regulating NF-κB activity

Cigarette smoking is an important risk factor for chronic obstructive pulmonary disease (COPD), yet its pathogenic mechanisms are not yet fully understood. Endothelial dysfunction is known to be involved in the pathogenesis of COPD. A detailed understanding of the mechanism involved in its progression would have a substantial impact on the optimization and development of treatment strategies. Here, we report that the expression of SIRT4, a mitochondrial sirtuin, is markedly down-regulated in cigarette smoke extract (CSE)-treated human pulmonary microvascular endothelial cells (HPMECs). Overexpression of SIRT4 significantly inhibits CSE-induced mononuclear cell adhesion to HPMECs. Consistently, we found that overexpression of SIRT4 attenuates the induction of vascular cell adhesion molecule 1 (VCAM-1) and E-selectin. Importantly, SIRT4 was found to negatively regulate CSE-induced NF-κB activation via inhibiting the degradation of IκBα. Moreover, we also found that proinflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and IL-6, the downstream target genes of NF-κB, are also inhibited by overexpression of SIRT4. These results suggest that SIRT4 protects HPMECs exposed to CSE stress via a mechanism that may involve the NF-κB pathway. Strategies based on the enhancement of SIRT4 may prove to be beneficial in the treatment of cigarette smoking caused COPD.     

Bronchodilation and safety of supratherapeutic doses of salbutamol or ipratropium bromide added to single dose GSK961081 in patients with moderate to severe COPD

BackgroundThere are few data on the bronchodilatory effects of adding short-acting bronchodilators (SABA) to maintenance, long-acting bronchodilator therapy. This study assessed the additional bronchodilation and safety of adding supratherapeutic doses of salbutamol (SALB) or ipratropium bromide (IPR) to the novel bi-functional molecule (or dual pharmacophore) GSK961081 400 μg (MABA 400) or 1200 μg (MABA 1200).MethodsThis randomised, double-blind, complete, crossover study in 44 patients with moderate to severe COPD, evaluated 6 treatments with a washout of at least 7 days between treatments: single doses of MABA 400 or MABA 1200 followed by cumulative doses of either SALB (3× 200 μg at 20 min intervals), IPR (20 μg, 20 μg and 40 μg at 20 min intervals) or placebo (PLA) (three doses at 20 min intervals) at 1 h, 12 h and 24 h post-MABA dose. The primary endpoint was maximal increase in FEV₁, from pre-dose bronchodilator (SABA/PLA), measured 15 min after each cumulative dose of SALB, IPR or PLA. Systemic pharmacodynamics (potassium, heart rate, glucose and QTc), adverse events and systemic pharmacokinetics were also assessed.ResultsThe additional bronchodilatory effects at 12 h and 24 h for both SALB and IPR were of a similar magnitude and statistically significant relative to PLA; mean differences (SE) (L) following MABA 400 dosing: 0.139 (0.023) after SALB at 12 h; 0.123 (0.022) after SALB at 24 h; 0.124 (0.023) after IPR at 12 h; 0.141 (0.021) after IPR at 24 h; and after MABA 1200 dosing: 0.091 (0.023) after SALB at 12 h; 0.126 (0.022) after SALB at 24 h; 0.055 (0.023) after IPR at 12 h; 0.122 (0.022) after IPR at 24 h. Any additional bronchodilator effects at 1 h were small and not clinically significantly different from PLA. There were small, non-clinically significant increases in mean heart rate after both MABA doses plus SALB, and decreased potassium levels in four patients after MABA 1200 plus SALB (×3) or PLA (×1) were observed but overall all treatments were well tolerated and raised no significant safety signals.ConclusionThe additional bronchodilation achieved following supratherapeutic doses of SALB and IPR on top of single doses of MABA 400 or 1200 was comparable for the two agents and neither were associated with any clinically relevant systemic pharmacodynamic effects other than the small transient hypokalemic effect in a 3 out of 41 patients receiving additional high dose salbutamol and MABA 1200. Either short-acting bronchodilator could potentially be used as rescue medication on top of MABA therapy.     

Acute Bronchodilator Response Has Limited Value in Differentiating Bronchial Asthma from COPD

Background. Acute responsiveness to inhaled bronchodilators is often used to differentiate between bronchial asthma and chronic obstructive pulmonary disease (COPD). The response can be expressed in terms of a change in FEV₁ and FVC in several ways—as absolute change, change as percent of baseline value, or as percent of predicted value with different thresholds for a positive test. A comprehensive evaluation of the diagnostic value of these different methods of expressing the acute bronchodilator response has not been carried out. Methodology. Response to inhaled salbutamol was measured by spirometry in 200 asthmatics and 154 patients with COPD. The sensitivity, specificity, and positive and negative predictive values of different methods of expressing responsiveness were calculated. Receiver operative characteristic curves were obtained. Results. None of the expressions of response gave a clear-cut separation between the two diseases. A ΔFEV₁≥ 0.2 L gave the most satisfactory combination of sensitivity (73%) and specificity (80%) and the highest positive (82%) and negative predictive values (69%) for diagnosing asthma. These values were superior to those obtained for the ERS or the ATS criteria for reversibility (ΔFEV₁%predicted ≥ 9% and ΔFEV₁ of ≥ than 12% and 0.2 L over the baseline, respectively), which had almost similar diagnostic characteristics. This was confirmed by the area under curve of the ROC plots. Expressions of response in terms of changes in FVC were unsatisfactory in separating the two diseases. Conclusions. It was concluded that the test of acute bronchodilator responsiveness has limited diagnostic value in separating asthma and COPD.     

Pfizer's dual-acting β2 agonists/muscarinic M3 antagonists

Bifunctional aromatic compounds that contain both β₂ agonist and muscarinic antagonist pharmacophores linked by a flexible lipophilic spacer are claimed. The compounds display nanomolar potency with respect to both activities and appear designed to provide a long duration of action. The compounds are claimed to be useful in the treatment of both asthma and chronic obstructive pulmonary disease.