Potential drug-drug interactions in hospitalized patients with chronic heart failure and chronic obstructive pulmonary disease

Introduction

Polypharmacy is common in patients with chronic heart failure (HF) and/or chronic obstructive pulmonary disease (COPD), but little is known about the prevalence and significance of drug-drug interactions (DDIs). This study evaluates DDIs in hospitalized patients.

Material and methods

We retrospectively screened medical charts over a 6-month period for diagnosis of chronic HF and/or COPD. Potential DDIs were evaluated using Lexi-Interact software.

Results

Seven hundred and seventy-eight patients were included in the study (median age 75 years, 61% men). The median number of drugs on admission and discharge was 6 (interquartile range (IQR) 4–9) and 7 (IQR 5–), respectively (p = 0.10). We recorded 6.5 ±5.7 potential DDIs per patient on admission and 7.2 ±5.6 on discharge (p = 0.2). From admission to discharge, type-C and type-X potential DDIs increased (p < 0.05 for both). Type X interactions were rare (< 1%), with the combination of a β-blocker and a β₂ agonist being the most common (64%). There were significantly more type-C and type-D potential DDIs in patients with chronic HF as compared to patients with COPD (p < 0.001). Patients with concomitant chronic HF and COPD had more type-C and type-X potential DDIs when compared to those with individual disease (p < 0.005). An aldosterone antagonist and ACE inhibitor/ARB were prescribed to 3% of chronic HF patients with estimated glomerular filtration rate < 30 ml/(min × 1.73 m²).

Conclusions

The DDIs are common in patients with chronic HF and/or COPD, but only a few appear to be of clinical significance. The increase in potential DDIs from admission to discharge may reflect better guideline implementation rather than poor clinical practice.     

Impact of chronic obstructive pulmonary disease on linear and nonlinear dynamics of heart rate variability in patients with heart failure

The objective of this study was to investigate the impact of chronic obstructive pulmonary disease (COPD)-heart failure (HF) coexistence on linear and nonlinear dynamics of heart rate variability (HRV). Forty-one patients (14 with COPD-HF and 27 HF) were enrolled and underwent pulmonary function and echocardiography evaluation to confirm the clinical diagnosis. Heart rate (HR) and R-R intervals (iRR) were collected during active postural maneuver (APM) [supine (10 min) to orthostasis (10 min)], respiratory sinus arrhythmia maneuver (RSA-M) (4 min), and analysis of frequency domain, time domain, and nonlinear HRV. We found expected autonomic response during orthostatic changes with reduction of mean iRR, root mean square of successive differences between heart beats (RMSSD), RR tri index, and high-frequency [HF (nu)] and an increased mean HR, low-frequency [LF (nu)], and LF/HF (nu) compared with supine only in HF patients (P<0.05). Patients with COPD-HF coexistence did not respond to postural change. In addition, in the orthostatic position, higher HF nu and lower LF nu and LF/HF (nu) were observed in COPD-HF compared with HF patients. HF patients showed an opposite response during RSA-M, with increased sympathetic modulation (LF nu) and reduced parasympathetic modulation (HF nu) (P<0.05) compared with COPD-HF patients. COPD-HF directly influenced cardiac autonomic modulation during active postural change and controlled breathing, demonstrating an autonomic imbalance during sympathetic and parasympathetic maneuvers compared with isolated HF.     

Total inspiratory and expiratory impedance in patients with severe chronic obstructive pulmonary disease

OBJECTIVES:

Several studies have confirmed the high potential of the forced oscillation technique for the assessment of respiratory modifications related to chronic obstructive pulmonary disease. However, most of these studies did not employ within-breath analyses of the respiratory system. The aim of this study is to analyze respiratory impedance alterations in different phases of the respiratory cycle of chronic obstructive pulmonary disease patients and to evaluate their clinical use.

METHODS:

39 individuals were evaluated, including 20 controls and 19 individuals with chronic obstructive pulmonary disease who experienced severe airway obstruction. We evaluated the mean respiratory impedance (Zm) as well as values for inspiration (Zi) and expiration cycles (Ze), at the beginning of inspiration (Zbi) and expiration (Zbe). The peak-to-peak impedance (Zpp), and the impedance change (ΔZrs) were also analyzed. The clinical usefulness was evaluated by investigating the sensibility, specificity and the area under the receiver operating characteristic curve.

RESULTS:

The respiratory impedance increased in individuals with chronic obstructive pulmonary disease in all of the studied parameters (Zm, Zi, Ze, Zbi, Zbe, ΔZrs and Zpp). These changes were inversely associated with spirometric parameters. Higher impedances were observed in the expiratory phase of individuals with chronic obstructive pulmonary disease. All of the studied parameters, except for ΔZrs (area under the receiver operating characteristic <0.8), exhibited high accuracy for clinical use (area under the receiver operating characteristic >0.90; Sensibility ≥ 0.85; Sp ≥ 0.85).

CONCLUSIONS:

The respiratory alterations in severe chronic obstructive pulmonary disease may be identified by the increase in respiratory system impedance, which is more evident in the expiratory phase. These results confirm the potential of within-breath analysis of respiratory impedance for the assessment of respiratory modifications related to chronic obstructive pulmonary disease.     

The relationship between self-efficacy and self-reported physical functioning in chronic obstructive pulmonary disease and chronic heart failure

In this study, the authors investigated whether self-reported physical functioning of patients with chronic obstructive pulmonary disease (COPD) and chronic systolic heart failure (CHF) was primarily explained by illness-specific differences related to diagnosis or whether more generic factors also contributed to their physical functioning. Consecutive patients with COPD (n = 56; mean age = 67.8, SD = 8.5) and CHF (n = 65; mean age = 60.0, SD = 10.2)from the outpatient clinics of a university hospital and a general hospital completed a self-report questionnaire, including the Rand-36 Health Survey, Cantril's ladder, the Mastery scale, the Perceived Health Competence Scale, and the Self-efficacy scale. COPD patients scored significantly worse in self-reported physical and psychological functioning and perceived health competence than did patients with CHF Regression analysis revealed that both the diagnosis and the illness severity contributed to self-reported physical functioning, although self-efficacy explained the main part of physical functioning. Therefore, important aims in the treatment of patients with COPD and CHF should be not only improving physical functioning but also enhancing self-efficacy.     

Handle with care: targeting neutrophils in chronic obstructive pulmonary disease and severe asthma?

Neutrophils play an important role in the pathogenesis of airway inflammation in both chronic obstructive pulmonary disease (COPD) and severe asthma. Currently available drugs have only limited effects on neutrophilic airway inflammation, particularily in COPD. Therefore, great efforts are undertaken to address neutrophilic inflammation in chronic respiratory disorders, in particular COPD. This review summarizes the rationale for anti-neutrophilic treatment in COPD and asthma and gives a critical overview of current developments in drug therapy. Moreover, unanswered questions and limitations of clinical trial design and choice of outcome parameters for proof-of-concept studies with novel anti-neutrophilic drugs are discussed as well as potential safety issues.     

Neurophysiological aspects and their relationship to clinical and functional impairment in patients with chronic obstructive pulmonary disease

OBJECTIVE:

The purpose was to assess functional (balance L–L and A–P displacement, sit‐to‐stand test (SST) and Tinetti scale – balance and gait) and neurophysiological aspects (patellar and Achilles reflex and strength) relating these responses to the BODE Index.

INTRODUCTION:

The neurophysiological alterations found in patients with chronic obstructive pulmonary disease (COPD) are associated with the severity of the disease. There is also involvement of peripheral muscle which, in combination with neurophysiological impairment, may further compromise the functional activity of these patients.

METHODS:

A cross‐sectional study design was used. Twenty‐two patients with moderate to very severe COPD (>60 years) and 16 age‐matched healthy volunteers served as the control group (CG). The subjects performed spirometry and several measures of static and dynamic balance, monosynaptic reflexes, peripheral muscle strength, SST and the 6‐minute walk test.

RESULTS:

The individuals with COPD had a reduced reflex response, 36.77±3.23 (p<0.05) and 43.54±6.60 (p<0.05), achieved a lower number repetitions on the SST 19.27±3.88 (p<0.05), exhibited lesser peripheral muscle strength on the femoral quadriceps muscle, 24.98±6.88 (p<0.05) and exhibited deficits in functional balance and gait on the Tinetti scale, 26.86±1.69 (p<0.05), compared with the CG. The BODE Index demonstrated correlations with balance assessment (determined by the Tinetti scale), r = 0.59 (p<0.05) and the sit‐to‐stand test, r = 0.78 (p<0.05).

CONCLUSIONS:

The individuals with COPD had functional and neurophysiological alterations in comparison with the control group. The BODE Index was correlated with the Tinetti scale and the SST. Both are functional tests, easy to administer, low cost and feasible, especially the SST. These results suggest a worse prognosis; however, more studies are needed to identify the causes of these changes and the repercussions that could result in their activities of daily living.     

Quality of life in patients with chronic obstructive pulmonary disease and comorbid anxiety or depression

The authors examined 179 veterans with chronic obstructive pulmonary disease (COPD) to determine the relative contribution of clinical depression and/or anxiety (Beck Depression and Beck Anxiety Inventories) to their quality of life (Chronic Respiratory Questionnaire and Medical Outcomes Survey Short Form). Multiple-regression procedures found that both depression and anxiety were significantly related to negative quality-of-life outcomes (anxiety with both mental and physical health quality-of-life outcomes, and depression primarily with mental health). When comorbid with COPD, mental health symptoms of depression and anxiety are some of the most salient factors associated with quality-of-life outcomes.     

Nonlinear analysis of heart rate variability of healthy subjects and patients with chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is one of the causes of mortality worldwide with an increasing prevalence. Heart rate variability (HRV) reflects the regulation mechanism of the cardiac activity by the autonomic nervous system. The assessment of HRV by using nonlinear methods is more sensitive for the detection of complexity when compared to linear methods. This study aims to get information about the autonomic dysfunction occurred in patients with COPD by analysing the complexity of HRV. Electrocardiogram signals recorded from healthy subjects, patients with moderate COPD and severe COPD (eight subjects per group) were analysed. The HRV signals were acquired from ECG signals. Signals were reconstructed in the phase space and largest Lyapunov exponent (LLE), correlation dimension, Hurst exponent and approximate entropy (ApEn) values were calculated. It has seen that for the patients with COPD LLE, correlation dimension, Hurst exponent and ApEn values were less than control group. According to this, HRV complexity decreases in the presence of COPD. However, there is no significant difference between COPD groups and the severity of COPD has no effect on the chaoticity of the system. The results revealed that autonomic dysfunction occurred in patients with COPD is associated with reduced HRV complexity.     

Responses to tiotropium in African-American and Caucasian patients with chronic obstructive pulmonary disease

Sparse information exists about chronic obstructive pulmonary disease (COPD) outcomes among different ethnic groups. To determine whether the effect of tiotropium on COPD exacerbation differs between African Americans and Caucasians, we performed a post hoc analysis of African-American (n = 150) and Caucasian (n = 1670) subgroups from a previously reported 6-month trial of tiotropium in patients with moderate-to-very-severe COPD. Compared with placebo, tiotropium reduced the likelihood of having at least 1 exacerbation in the entire group (RR, 0.81; 95% CI, 0.66-0.99, P = 0.037) with no statistically significant difference between African-American and Caucasian subgroups (P = 0.34). For African Americans, tiotropium significantly reduced the number of antibiotic days for COPD, hospitalizations for exacerbations, and hospitalization days for COPD. For Caucasians, tiotropium significantly reduced the number of exacerbations, exacerbation days, unscheduled clinic visits for COPD, and hospitalizations for exacerbations. Tiotropium reduced the frequencies of antibiotic days and of COPD hospital days to a significantly greater extent in African Americans compared with Caucasians (P = 0.027 and P = 0.025, respectively). No statistically significant ethnic-related differences were observed in the effect of tiotropium on the frequencies of exacerbations, exacerbation days, systemic corticosteroid days, unscheduled clinic visits, or COPD hospitalizations. Spirometry improved to a similar extent in both subgroups for the entire duration of the 6-month trial. African Americans used fewer respiratory medications than Caucasians in this study. We conclude that tiotropium reduces COPD exacerbations and associated health-care use to a similar extent in African Americans compared with Caucasians.     

Association of serotonin transporter gene variation with smoking, chronic obstructive pulmonary disease, and its depressive symptoms

A serotonin transporter gene, SLC6A4, is thought to be related to nicotine dependence and depression, one of the comorbidities of chronic obstructive pulmonary disease (COPD). To investigate the association between SLC6A4 variation and tobacco consumption, susceptibility to COPD, and depression status. In all, 247 patients with COPD and 119 control subjects were genotyped for 5 tag single-nucleotide polymorphisms (SNPs) of SLC6A4. We analyzed the correlation between these genotypes and COPD, using the results of a pulmonary function test or chest computed tomography; data on tobacco consumption (pack-years); and the depression score based on the hospital anxiety and depression scale (HADS) after adjusting for age, gender, and smoking status (and pack-years, when appropriate). The rare allele rs2020936 was significantly associated with COPD incidence in the trend model (P = 0.003; odds ratio, 2.20; 95% confidence interval, 1.31-3.74). This allele was also associated with the number of pack-years (P = 0.026). The major allele of another SNP of SLC6A4, namely rs3794808, correlated with the HADS depression score (P = 0.016). We conclude that SLC6A4 variation affects COPD pathogenesis, and this effect depends partly on tobacco consumption. SLC6A4 variation also affects depressive symptoms. SLC6A4 could be modified to prevent COPD and treat the depressive symptoms of COPD.     

慢性阻塞性肺病患者冷敏受体高表达及其临床意义

目的 探讨瞬时受体电位蛋白-8(TRPM8)在慢性阻塞性肺病(COPD)患者与正常人气道黏膜上皮组织的表达差异及其信号传导机制.方法 免疫组化法观察TRPM8蛋白在气道黏膜上皮分布特点及表达差异,RT-PCR及Western bolt检测TRPM8 mRNA及其蛋白表达.体外培养16HBE细胞(n=5),分为对照组(37℃)、冷刺激组、冷刺激+BCTC组、冷刺激+转染TRPM8 shRNA组、冷刺激+转染对照组,以18℃冷空气刺激细胞,激光共聚焦检测胞内Ca2+相对浓度.结果 TRPM8蛋白主要分布于支气管黏膜上皮基底细胞或小颗粒细胞的细胞膜,COPD组累积吸光度/面积比值、TRPM8 mRNA及其蛋白表达量显著高于对照组(P＜0.05).冷刺激组的Ca2+浓度显著高于对照组(P＜0.05),BCTC、转染TRPM8 shRNA组较前者明显下降(P＜0.05).结论 COPD患者气道黏膜上皮TRPM8蛋白高表达可能是其对冷空气敏感的重要原因之一.     

Daily activities are sufficient to induce dynamic pulmonary hyperinflation and dyspnea in chronic obstructive pulmonary disease patients

OBJECTIVE:

The aim of this study was to measure dynamic lung hyperinflation and its influence on dyspnea perception in moderate and severe chronic obstructive pulmonary disease patients after performing activities of daily living.

METHODS:

We measured inspiratory capacity, sensation of dyspnea, peripheral oxygen saturation, heart rate and respiratory rate in 19 chronic obstructive pulmonary disease patients. These measurements were taken at rest and after performing activities of daily living (e.g., going up and down a set of stairs, going up and down a ramp and sweeping and mopping a room).

RESULT:

The inspiratory capacity of patients at rest was significantly decreased compared to the capacity of patients after performing activities. The change in inspiratory capacity was -0.67 L after going up and down a ramp, -0.46 L after sweeping and mopping a room, and -0.55 L after climbing up and down a set of stairs. Dyspnea perception increased significantly between rest, sweeping and mopping, and going up and down a set of stairs. Dyspnea perception correlated positively with inspiratory capacity variation (r = 0.85) and respiratory rate (r = 0.37) and negatively with peripheral oxygen saturation (r = -0.28).

CONCLUSION:

Chronic obstructive pulmonary disease patients exhibited reductions in inspiratory capacity and increases in dyspnea perception during commonly performed activities of daily living, which may limit physical performance in these patients.     

Excess hospital admissions for pneumonia, chronic obstructive pulmonary disease, and heart failure during influenza seasons in Hong Kong

It is widely held that Southern China is a hypothetical influenza epicentre for the emergence of pandemic influenza viruses. However, influenza is perceived as a relatively unimportant infection in this part of the world compared with western countries. Hong Kong is situated within the hypothetical epicentre and serves as a sentinel post for the region. In a retrospective study, the influenza-associated excess hospitalisations in a regional hospital for pneumonia, chronic obstructive pulmonary disease (COPD), heart failure, and asthma in persons aged > or = 65 years from 1998 to 2001 were each estimated by a model taking into consideration the confounding effect of other respiratory viral infections, seasonal factors, time trends, and weather and pollution indices. In the regression models, influenza activity is an independent significant factor affecting admission rates for pneumonia, COPD, and heart failure but not that for asthma. The variations in hospital admissions for pneumonia, COPD, and heart failure explained by influenza activity were 38.9, 7.5, and 45.6%, respectively. The adjusted rates of excess influenza-associated hospital admissions for the three diagnoses combined amounted to 58.5, 20.0, 29.2, and 13.4 per 10,000 populations aged > or = 65 years in 1998, 1999, 2000, and 2001, respectively. In conclusion, influenza activity is associated significant excess hospital admissions among elderly aged 65 or above in Hong Kong, comparable to the data reported in Western countries. The findings support a wider application of annual influenza vaccination in this region.     

Acute effects of different levels of continuous positive airway pressure on cardiac autonomic modulation in chronic heart failure and chronic obstructive pulmonary disease

Introduction

Non-invasive ventilation may improve autonomic modulation and ventilatory parameters in severely disabled patients. The aim of the present study was to evaluate the physiological influence of acute treatment with different levels of continuous positive airway pressure (CPAP) on the autonomic balance of heart and respiratory responses in patients with stable chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF).

Materials and methods

A COPD group (n = 10), CHF group (n = 8) and healthy subjects (n = 10) were evaluated. The participants were randomized to receive three different levels of CPAP on the same day: sham ventilation (Sham), 5 cmH₂0 (CPAP5) and 10 cmH₂0 (CPAP10) for 10 min. Respiratory rate, end tidal carbon dioxide (E_TCO₂), peripheral oxygen saturation (SpO₂), heart rate (HR), blood pressure and heart rate variability in the time and frequency domains were measured during spontaneous breathing and under the sham, CPAP5 and CPAP10 conditions.

Results

All groups experienced a reduction in E_TCO₂ values during treatment with CPAP (p < 0.05). CPAP increased SpO₂ and HR in the COPD group (p < 0.05). The COPD group also had lower RMSSD values during treatment with different levels of CPAP when compared to the control group (p < 0.05). In the CHF group, CPAP5 and CPAP10 increased the SDNN value (p < 0.05). CPAP10 reduced the SDNN value in the COPD group (p < 0.05).

Conclusion

The findings suggest that CPAP may cause improvements in the neural control of heart rate in patients with stable COPD and CHF. For each patient, the “best CPAP level” should be defined as the best respiratory response and autonomic balance.     

Self-management abilities, physical health and depressive symptoms among patients with cardiovascular diseases, chronic obstructive pulmonary disease, and diabetes

Objective

This study aimed to identify the predictive role of direct resources (educational level and marital status) and self-management abilities on physical health and depressive symptoms in patients with cardiovascular diseases (CVD), diabetes, or chronic obstructive pulmonary disease (COPD).

Methods

Our cross-sectional questionnaire-based study included 1570 CVD patients, 917 COPD patients, and 412 patients with diabetes.

Results

Physical health and depressive symptoms of COPD patients was lower than those of CVD and diabetic patients. Correlation analyses indicated that self-management abilities were strong indicators for physical health and depressive symptoms (all p < 0.001). This relationship was strongest for depressive symptoms. Self-management abilities were related to educational level in all groups (all p < 0.001). Regression analyses revealed that self-management abilities were strong predictors of physical health and depressive symptoms in all three patient groups (all p < 0.001).

Conclusion

This research showed that self-management abilities are strong predictors of physical health and depressive symptoms.

Practice implications

Interventions that improve self-management abilities may counteract a decline in physical health and depressive symptoms. Such interventions may be important tools in the prevention of the loss of self-management abilities, because they may motivate people who are not yet experiencing serious problems.     

Improvement in mood, physical symptoms, and function with nortriptyline for depression in patients with chronic obstructive pulmonary disease.

Although recent epidemiologic studies have established that patients with chronic medical illness and depressed mood are more disabled than euthymic patients, detailed data on the benefits and risks of antidepressant treatment in medically high-risk patients have been slow to accumulate. The authors have examined multiple outcome indicators in patients with disabling chronic obstructive pulmonary disease and comorbid depression. Thirty patients completed a 12-week, randomized controlled trial of nortriptyline. Nortriptyline was clearly superior to placebo for treatment of depression. Nortriptyline treatment was accompanied by marked improvements in anxiety, certain respiratory symptoms, overall physical comfort, and day-to-day function; placebo effects were negligible. Physiological measures reflecting pulmonary insufficiency were generally unaffected by treatment. These data provide impetus for renewed efforts to improve recognition and treatment of mood disorders in even severely disabled medical patients.     

Influenza vaccination and risk of respiratory failure in patients with chronic obstructive pulmonary disease: A nationwide population-based case-cohort study

Background

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease which causes a considerable disease burden. Patients with COPD are at a higher risk for influenza infection and influenza vaccination are recommended at this high risk patient group. In the current study, we aimed to evaluate the association between influenza vaccination and the risk of respiratory failure (RF) in COPD patients.

Thyroid status and nephron loss--a study in patients with chronic renal failure, end stage renal disease and/or on hemodialysis

Thyroid function was measured in 30 healthy subjects and 84 patients with various degrees of nephron loss (GRF: 70 +/- 15 m/min, 30 +/- 16 ml/min, 10 +/- 7 ml/min and 2.1 +/- 1.3 ml/min). A low T3 and T4 syndrome is evident when GRF is reduced to 30 +/- 16 ml/min while a blunted TSH response is detected earlier in the course of nephron loss. T3 response to TRH was normal and FT4 was not affected by renal dysfunction. The data indicate that in nephron loss hypothalamic-pituitary abnormalities occur.