Correlation between bronchodilator responsiveness and quality of life in chronic obstructive pulmonary disease.

BACKGROUND: Guidelines and literature debate the importance of testing for bronchial reversibility and its total significance is unclear. Clinically, patients with greater reversibility have higher fluctuations in respiratory symptoms, and hence may have a reduced health-related quality of life (HRQoL). On the other hand, they may have a better HRQoL as medications may be more effective in this population. Presently, there are no reports concerning the relationship between HRQoL as an indicator of therapy and reversibility. We hypothesized that the reversibility of airflow limitation might be correlated with the HRQoL in COPD. METHODS: We examined 63 subjects with COPD (mean age: 71.7 years). Reversibility was measured by the change in FEV1 and FVC after the inhalation of salbutamol (300 microg), and we investigated the relationship between the reversibility and the parameters of HRQoL, which included St. George's Respiratory Questionnaire (SGRQ), Visual analogue scale-8 (VAS-8), Short-Form 36-Item Health Study, Basic activities of daily living, Instrumental activities of daily living, and the Oxygen cost diagram. RESULTS: Post-bronchodilator FEV1, % predicted was positively correlated with both the total scores of SGRQ and VAS-8 (p<0.0001 and p<0.006, respectively). Furthermore, the reversibility of FVC was positively correlated with all items of the SGRQ, except for impact (total score: p<0.02; symptoms: p<0.02; activity, p<0.05; total score of VAS-8: p<0.02). However, the reversibility of FEV1 was neither correlated with the total score nor any items in the scales. CONCLUSIONS: Those who have FVC that respond to bronchodilator at rest might result in an improvement of HRQoL after treatment.     

Acute bronchodilator trials in chronic obstructive pulmonary disease.

Short-term trials of bronchodilator drugs are widely used to assess patients with stable chronic obstructive pulmonary disease (COPD), but there is an uncertainty about the equivalence of the FEV1 response to beta-agonists and anticholinergic drugs, their relative ability to identify patients likely to improve with corticosteroids, the most appropriate way to express the results of these tests, and whether age or allergic status affects the beta-agonist and anticholinergic response differently. We studied 100 consecutive patients with stable COPD (mean FEV1, 0.96 +/- 0.48 L; mean age, 62 +/- 8 yr). Spirometry was measured before and after either 5 mg of nebulized salbutamol or 500 micrograms of nebulized ipratropium bromide and repeated after 2 wk of 30 mg of oral prednisolone daily. Total IgE, specific RAST, and skin prick testing values were recorded. Using modified American Thoracic Society response criteria, 33 patients failed to bronchodilate after the acute trials, 16 responded only to nebulized salbutamol, 17 to nebulized ipratropium, and 34 to both drugs. Twenty-two patients improved after corticosteroids. This was usually detected by a positive acute trial response (salbutamol 90% specific; ipratropium 84% specific). Baseline FEV1 differed between days, and in those who responded on only 1 day, this variation correlating with the response to ipratropium (r = 0.66). Expressing the response criterion as a percentage change in the available bronchodilatation increased the numbers responding with a high baseline FEV1, and vice versa. Neither age nor allergic status was related to the change in FEV1 after either drug in these patients. In COPD patients, testing with high-dose nebulized bronchodilators identifies a substantial number of partially reversible patients whatever age it is employed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Remodeling in asthma and chronic obstructive pulmonary disease

Airway and lung tissue remodeling and fibrosis play an important role in the development of symptoms associated with lung function loss in asthma and chronic obstructive pulmonary disease (COPD). In the past decades, much attention has been paid to the inflammatory cellular process involved in airway remodeling in these two diseases. However, it is increasingly clear that resident cells contribute to airway and lung tissue remodeling and to associated fibrosis as well. This article deals with some new aspects and discusses the role of vasculature and vascular endothelial growth factor in the development of airway obstruction and airway wall fibrosis in asthma and COPD. Moreover, it addresses the extracellular matrix (ECM) turnover as present in both asthma and COPD. All components of lung ECM (collagen, elastic fibers, proteoglycans) have been shown to be potentially altered in these two diseases. Finally, the interaction between transforming growth factor (TGF), Smad signaling, and TGF in the ECM turnover will be discussed. We propose that ECM damage and repair contribute to airway and lung tissue pathology and that the vasculature may enhance this process. The localization of this process is dependent on the etiology of the disease (i.e., allergen-driven in asthma and smoke-driven in COPD) and the local environment in which the pathologic process takes place.     

Overlap of asthma and chronic obstructive pulmonary disease

PURPOSE OF REVIEW: Asthma and chronic obstructive pulmonary disease (COPD) are both defined by the presence of airflow obstruction, but they present distinguishing differences in terms of both risk factors and clinical phenotypes. Yet it is quite common in the clinical setting to observe patients with asthma showing COPD-like phenotypes, and vice versa, making it a priority to search for optimal prevention, treatment, and management strategies for these cases of coexisting lung obstructive diseases. RECENT FINDINGS: Recent studies have provided further evidence of strong epidemiologic and clinical links between asthma and COPD. Adult subjects with active asthma are as much as 12 times more likely to acquire COPD over time than subjects with no active asthma. Signs identifying patients with asthma predisposed to developing COPD may already be present at the early stages of the disease, a finding with potential implications for prevention of COPD. In addition to spirometry and other pulmonary function tests (such as measurements of residual volume and diffusing capacity of the lung for carbon monoxide), recent evidence suggests that the assessment of type and degree of airway remodeling and the evaluation of inflammatory markers might prove useful in the future to characterize phenotypically patients with coexisting asthma and COPD. SUMMARY: The nature of the association between asthma and COPD remains unclear and open to discussion. Further research is required to develop effective management algorithms for patients with multiple obstructive lung diseases, determine to what extent early treatment and optimal management of asthma may protect against progression into COPD, and identify genetic markers of individual susceptibility to specific lung disease phenotypes and pharmacologic treatments.     

The bronchodilator test in chronic obstructive pulmonary disease: interpretation methods

The objective of the study was to evaluate the best method for interpreting the bronchodilator test (BDT). Five formulas for expressing the BDT results were analyzed and compared: changes experienced by maximum expiratory volume in 1s (FEV(1)) and forced vital capacity (FVC) measured in milliliters, in percentage with respect to the baseline, in percentage with respect to the predicted, in percentage with respect to the possible, and in standardized residuals. Ninety-eight chronic obstructive pulmonary disease (COPD) patients were submitted to a respiratory function test on two different days. On each occasion three spirometries were conducted: basal, post-placebo and post bronchodilator. As a gold standard, a normality interval was defined using the variability experienced with the placebo between the two days of the study. The best formulas according to their sensitivity, specivity and area under receiver operating characteristic (ROC) curve were the "standardized residuals", with a cut point of .3, and the "percentage with respect to the predicted" with a cut point of 6%.     

不同程度的慢性阻塞性肺疾病对支气管舒张试验的反应性差异

目的 探讨不同严重程度的慢性阻塞性肺疾病( COPD)患者对支气管舒张试验的反应性差异.方法 入选Ⅰ～Ⅳ级COPD稳定期患者共411例,采用支气管舒张试验比较支气管舒张前后第1秒用力呼气容积(FEV1)、用力肺活量(FVC)和深吸气量(IC)的改变值和改变率.结果 支气管舒张试验后,COPD患者的FEV1、FVC和IC均有增加,比试验前差异有统计学意义(P＜0.01).随着COPD严重程度的增加,FEV1的改变值逐渐减少,而FVC和IC改变值却逐渐增加.结论 随着COPD的严重程度加重,吸入支气管舒张剂后,FVC和IC改变值越大,FVC和IC是重度COPD患者对支气管舒张剂反应性的指标.     

Adenosine signaling in asthma and chronic obstructive pulmonary disease

PURPOSE OF REVIEW: The chronic lung diseases, asthma and chronic obstructive pulmonary disease, are pulmonary disorders in which persistent inflammation and alterations in lung structure contribute to a progressive loss of lung function. Although the exact type of inflammation and damage in each disease is distinct, they share the common feature that they are chronic in nature. Despite efforts, little is known about the cellular and molecular mechanisms that drive the chronicity of these two diseases. This review will summarize important findings regarding the role of adenosine, a signaling nucleoside implicated in the pathogenesis of these two disorders. RECENT FINDINGS: Aerosolized adenosine induces bronchoconstriction in patients with asthma and chronic obstructive pulmonary disease primarily through the release of mast cell mediators. In this setting it can not only be used to aid in diagnosis but also to monitor patient responses to steroid therapy. Adenosine levels are elevated in the lungs of asthma patients, indicating greater flux through adenosine receptor signaling pathways. In-vitro studies have shown adenosine to access pathways leading to the genesis of chronic inflammation via the release of proinflammatory cytokines and chemokines. Animal studies demonstrate that merely elevating adenosine levels in the mouse is sufficient to induce a pulmonary phenotype with features of asthma and chronic obstructive pulmonary disease. SUMMARY: Identifying mediators regulating the chronic nature of asthma and chronic obstructive pulmonary disease is critical towards advancements in treatment options. Adenosine has been implicated in promoting the inflammation and airway remodeling seen in chronic lung disease and thus makes an attractive therapeutic target.     

Predictors of cardiovascular disease in asthma and chronic obstructive pulmonary disease

Background

Cardiovascular disease (CVD) is a common comorbidity in patients with chronic airway obstruction, and is associated with systemic inflammation and airway obstruction. The aim of this study was to evaluate the predictors of CVD in two different conditions causing chronic airway obstruction, asthma and COPD.

Methods

Lung function tests, clinical and echocardiographic data were assessed in 229 consecutive patients, 100 with asthma and 129 with COPD. CVD was classified into: pressure overload (PO) and volume overload (VO). Sub-analysis of patients with ischemic heart disease (IHD) and pulmonary hypertension (PH) was also performed.

Results

CVD was found in 185 patients (81%: 51% COPD and 30% asthmatics) and consisted of PO in 42% and of VO in 38% patients. COPD patients, as compared to asthmatics, had older age, more severe airway obstruction, higher prevalence of males, of smokers, and of CVD (91% vs 68%), either PO (46% vs 38%) or VO (45% vs 30%). CVD was associated with older age and more severe airway obstruction both in asthma and COPD. In the overall patients the predictive factors of CVD were age, COPD, and male sex; those of PO were COPD, BMI, VC, FEV₁ and MEF₅₀ and those of VO were age, VC and MEF₅₀. In asthma, the predictors of CVD were VC, FEV₁, FEV₁ /VC%, and PaO₂, those of PO were VC, FEV₁ and FEV₁ /VC%, while for VO there was no predictor. In COPD the predictors of CVD were age, GOLD class and sex, those of VO age, VC and MEF₅₀, and that of PO was BMI. Sub-analysis showed that IHD was predicted by COPD, age, BMI and FEV₁, while PH (found only in 25 COPD patients), was predicted by VO (present in 80% of the patients) and FEV₁. In subjects aged 65 years or more the prevalence of CVD, PO and VO was similar in asthmatic and COPD patients, but COPD patients had higher prevalence of males, smokers, IHD, PH, lower FEV₁ and higher CRP.

Conclusions

The results of this study indicate that cardiovascular diseases are frequent in patients with chronic obstructive disorders, particularly in COPD patients. The strongest predictors of CVD are age and airway obstruction. COPD patients have higher prevalence of ischemic heart disease and pulmonary hypertension. In the elderly the prevalence of PO and VO in asthma and COPD patients is similar.

     

慢性阻塞性肺疾病支气管舒张试验后肺容量和呼气流量反应的差别

目的 探讨支气管舒张试验后COPD患者的肺容量和呼气流量反应的差别.方法 2006年1月至2008年6月临床诊断为COPD稳定期无呼吸衰竭及心力衰竭的患者465例,其中男426例,女39例;年龄(42～86)岁,平均(67±8)岁.采用支气管舒张试验比较患者支气管舒张前后FEV_1和FVC的改变值和改变率.统计学分析采用自身配对t检验和配对秩和检验,各组间比较采用独立样本t检验和方差分析(正态分布)以及非参数秩和检验(非正态分布).结果 支气管舒张试验后,COPD患者的FEV_1平均增加117 ml,较基础值平均提高13.2%,舒张试验阳性率为18.7%(87/465);FVC平均增加258 ml,较基础值平均提高14.0%,舒张试验阳性率为44.1%(205/465).随着COPD严重程度的增加,FEV_1改变值逐渐减少,而FVC改变值却逐渐增加.结论 吸入支气管舒张剂后COPD患者的容量反应较流量反应更为明显,FVC改变值较FEV_1更大,且随着COPD的严重程度增加,FVC增加值越大.FVC应该作为COPD患者对支气管舒张剂反应的重要指标.     

外周血白介素-17检测在气道慢性炎症性疾病诊断中的临床价值

目的探讨外周血CD4+T细胞亚群Th17代表性细胞因子IL-17在哮喘、慢性阻塞性肺疾病(COPD)以及哮喘COPD重叠综合征(ACOS)等气道慢性炎症性疾病鉴别诊断中的临床价值。方法收集哮喘患者26例、COPD患者33例及ACOS患者14例的血清、临床资料及实验室检查资料,检测哮喘、COPD、ACOS患者外周血IL-17等细胞因子、炎症介质、外周血白细胞分类计数、血清免疫球蛋白亚型以及肺通气功能,并进行组间比较。健康体检者69例作为对照。结果 Th17细胞因子IL-17在哮喘及ACOS组升高较COPD组更为明显(P0.01)。调节性T细胞的主要细胞因子IL-10在哮喘患者中的水平明显低于COPD患者(P0.05)。外周血炎症细胞比例、免疫球蛋白亚型在哮喘、COPD、ACOS鉴别诊断中具有一定参考价值。但肺通气功能指标对于以上三者的鉴别价值有限。哮喘及ACOS组患IL-17与肺通气功能指标呈负相关关系。结论 IL-17作为新型Th17细胞分泌的代表性细胞因子,在鉴别上述疾病中具有重要的参考价值。Th17/Treg细胞失衡可能是难治性哮喘的潜在发病机制。     

Exacerbations and progression of disease in asthma and chronic obstructive pulmonary disease

Exacerbations, characterized by an increase in patients' symptoms above baseline, are characteristic of both chronic obstructive pulmonary disease (COPD) and asthma. Prevention of exacerbations and their expedient treatment are major goals for reducing the morbidity and cost of both conditions. Exacerbations, however, may also adversely affect the natural history of these disorders, perhaps by contributing to increased rates of lung function decline, systemic effects, and premature mortality. Although the available information is limited, the course of COPD is affected adversely by exacerbations in multiple ways. First, exacerbations likely lead to structural alterations in the lung and to permanently worsened airflow. Second, health status is adversely affected by exacerbations, and although the mechanisms are unclear, the effects are long lasting and may be irreversible. Less is known in asthma about the effect of exacerbations on natural history, but many of the same pathogenetic processes involved in COPD exacerbations likely play a role in some subjects with asthma as well. Future studies of how exacerbation affects the "natural history" of asthma and COPD will require a better understanding of the heterogeneity of exacerbations but promises to identify new therapeutic strategies to treat these disorders.     

Role of indacaterol,a once-daily bronchodilator,in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow obstruction that can lead to lung destruction and dyspnea. Although there has been a slight reduction in mortality in recent decades, COPD is still a serious health problem that has enormous costs and utilizes significant medical resources. There have been a number of pharmacologic interventions that have been developed for the treatment of COPD. Current guidelines recommend the use of long-acting bronchodilators for the treatment of moderate and severe stage COPD, since they have been shown to improve lung function, respiratory symptoms, and quality of life. Indacaterol is a once-daily beta2-agonist (β2-agonist) delivered by a single-dose dry powder inhaler used for the treatment of COPD. It is currently approved at a dose of 75 μg in the United States and a dose of 150 μg with a maximal dose of 300 μg in Europe and other countries. Several studies show that indacaterol was statistically superior to both long-acting β2-agonist, formoterol and salmeterol, as well as, noninferior to tiotropium. Indacaterol is generally well tolerated and has a good safety profile. Other studies show that there is an additive bronchodilator response with the addition of indacaterol to tiotropium, which would provide a once-daily treatment option for patient with moderate to severe COPD. This review discusses the pharmacokinetic, comparative efficacy and safety data for indacaterol.KEYWORDS : Indacaterol, chronic obstructive pulmonary disease (COPD), long-acting beta2-agonist (β2-agonist), tiotropium, salmeterol, formoterol, bronchodilator     

Comparison of serum biomarkers between patients with asthma and with chronic obstructive pulmonary disease

Objective: Asthma and chronic obstructive pulmonary disease (COPD) have distinct pathophysiological mechanisms but sometimes share similar clinical manifestations. Distinguishing between these diseases is important. This study compared the profiles of serum biomarkers between patients with asthma and those with COPD. Methods: Serum levels of the chitinase like protein YKL-40, periostin, interleukin (IL)-18, and chemokine (C--C motif) ligand 18 (CCL18) were measured in asthma patients (n = 20), COPD patients (n = 16), and normal controls (n = 20). Results: Serum levels of YKL-40 were higher in COPD patients [median (range), 55 (17–565) versus 208 (74–922) ng/mL, p < 0.0001], but no differences were observed between asthma and COPD patients after adjusting for age and forced expiratory volume in 1 s (FEV₁). No differences in serum levels of periostin, IL-18, or CCL18 were observed between the patient groups. Total IgE and airway hypersensitivity were negatively correlated (r = ?0.485, p = 0.007). CCL18 levels were related to patients’ age in asthmatic patients (r = ?0.562, p = 0.010). Serum levels of CCL18 and IL-18 were positively correlated in patients with COPD (r = 0.696, p = 0.003). Conclusions: No differences in the serum profiles of periostin, IL-18, or CCL18 were observed between patients with asthma and those with COPD. Serum levels of YKL-40 were not different between asthma and COPD patients after adjusting for age and FEV₁. There were negative correlation between CCL18 and age in patients with asthma and positive correlation between IL-18 and CCL18 in patients with COPD.     

Sleep in patients with asthma and chronic obstructive pulmonary disease

Sleep abnormalities are common in patients with asthma and chronic obstructive pulmonary disease. Recent studies have provided new insight into the mechanisms involved in circadian changes in airway resistance, analyzed the effect of disease treatment on sleep quality, and re-examined issues relating to oxygen supplementation at night in patients with chronic obstructive pulmonary disease. Although providing new and useful information, some of these studies also raise new questions that will need answering in the future. This article reviews our current understanding of the complex interactions between sleep and lung disease in patients with asthma and chronic obstructive pulmonary disease.     

Role of ventilatory drive in asthma and chronic obstructive pulmonary disease

The ventilatory drive is affected by several factors such as chemosensitivity, basal arterial oxygen or carbon dioxide tension, mechanical impedance, and respiratory muscle dysfunction. Blunted ventilatory drive or a decrease in the perception of dyspnea in bronchial asthma and chronic obstructive pulmonary disease (COPD) could lead to a decrease in the alarm reaction to dangerous situations such as severe airway obstruction, severe hypoxemia, or severe hypercapnia. This could delay management and treatment, causing an increase in the morbidity and mortality of patients with bronchial asthma and COPD. The ventilatory drive to chemical stimuli can be altered by a beta-2-agonist, oxygen administration; and lung volume reduction, and an increased dyspnea sensation may be improved by corticosteroid, chest wall vibration, or lung volume reduction. The ventilatory drive has been found to play a key role in determining the severity of asthma and COPD.     

Mechanisms of bronchial hyperreactivity in asthma and chronic obstructive pulmonary disease

Bronchial hyperreactivity has long been recognized as a hallmark of chronic asthma. Less is known about the prevalence and mechanisms of hyperreactivity in chronic obstructive pulmonary disease (COPD). Currently, it is unclear whether the role and mechanisms of hyperreactivity are similar in patients with asthma and COPD or whether the underlying pathophysiologic abnormalities are different for both diseases. The aim of this review is to present an overview of current knowledge of the mechanisms of bronchial hyperreactivity in asthma and COPD.     

Diagnosis of chronic obstructive pulmonary disease and differentiation from asthma

Asthma and chronic obstructive pulmonary disease are both common diseases, which together afflict approximately 25 million Americans. Although expiratory airflow obstruction is the common physiologic abnormality, asthma and chronic obstructive pulmonary disease are characterized by unique pathologic findings, clues from clinical histories, and laboratory test results. Despite some overlap in these characteristics, it is usually possible to differentiate these two conditions. This distinction is important for the healthcare provider to communicate a realistic prognosis to the patient and the patient's family, and to institute appropriate therapy.