COPD is not COPD is not allergy.

Chronic obstructive pulmonary disease (COPD) is still a poorly understood disease. Its pathogenesis is excitingly complex and has systemic consequences caused not only by increased production of certain cytokines but also by neurohumoral activation, chronic bacterial infection, muscle wasting and cachexia. Asthma and COPD have many overlapping clinical features so it should not be surprising that in the pathogenesis of COPD mediators such as leukotrienes, complement activation, atopic or even autoimmune processes are possibly involved. The pathogenesis of cardiovascular system involvement in COPD is also multifaceted and includes chronic heart hypoxia, damage by smoking and pulmonary hypertension; it must also be viewed as a consequence of systemic inflammation and neurohormonal activation. COPD is among the leading causes of morbidity and mortality worldwide and therefore it should be studied intensively beyond the lung itself. Treatments directed at neurohumoral activation in COPD have not been fully addressed; this aspect of COPD should be better understood, as it may direct novel therapeutic approaches.

Distribution of self-rated health and association with clinical parameters in patients with chronic obstructive pulmonary disease.

BACKGROUND: Data on self-rated health (SRH) in patients with chronic obstructive pulmonary disease (COPD) are very limited; we therefore initiated this study to investigate the distribution of SRH and association with established parameters of disease severity. PATIENTS AND METHODS: We included 135 clinically stable patients with COPD (64 +/- 8 years, 71% men, GOLD stage: II -59; III -55; IV -21) and 25 healthy control persons. SRH was evaluated using the 5-grade Likert scale (1-very poor to 5-very good). RESULTS: Patients with COPD had poorer SRH when compared with controls (3.0 +/- 0.7 vs. 3.8 +/- 0.6, P < 0.001). SRH decreased over GOLD stage (P = 0.016) and 27 (20%) patients reported poor or very poor SRH. In univariate analysis, GOLD stage (P = 0.022), Center for Epidemiologic Studies Depression (CES-D) score (P = 0.001), BODE index score (P < 0.001), score on the modified Medical Research Council (MMRC) dyspnea scale (P < 0.001) and 6-minute walk test (6MWT) distance (P < 0.001) determined poor or very poor SRH. In a multivariate model which included BODE index score, a CES-D score > or = 16 (P = 0.013) and BODE index score (P = 0.012) determined poor or very poor SRH. In the model with individual components of the BODE index, a CES-D score > or = 16 (P = 0.012), MMRC score of 3 or 4 (P = 0.019) and 6MWT distance < or = 249 m (P = 0.019) determined poor or very poor SRH. CONCLUSION: In patients with COPD, SRH is worse than in healthy control persons and deteriorates over GOLD stage. Perception of health as poor or very poor is associated with psychological components (CES-D score) and disease severity (BODE index score, 6MWT distance and MMRC dyspnea score).

Clinical-pharmacist intervention reduces clinically relevant drug-drug interactions in patients with heart failure: A randomized, double-blind, controlled trial.

BACKGROUND: Incidence of drug-drug interactions (DDIs) increases with complexity of treatment and comorbidities, as in heart failure (HF). This randomized, double-blind study evaluated the intervention of the pharmacist on prevalence of clinically relevant DDIs (NCT01855165). METHODS: Patients admitted with HF were screened for clinically relevant DDIs, and randomized to control or intervention. All attending physicians received standard advice about pharmacological therapy; those in the intervention group also received alerts about clinically relevant DDIs. Primary endpoint was DDI at discharge and secondary were re-hospitalization or death during follow-up. RESULTS: Of 213 patients, 51 (mean age, 79 ± 6 years; male, 47%) showed 66 clinically relevant DDIs and were randomized. For intervention (n=26) versus control (n=25), the number of patients with and the number of DDIs were significantly lower at discharge: 8 vs. 18 and 10 vs. 31; p=0.003 and 0.0049, respectively. Over a 6 month follow-up period, 11 control and 9 intervention patients were re-hospitalized or died (p>0.2 for all). No significant differences were seen between control and intervention for patients with eGFR <60 mL/min/1.73 m(2) (78%) for re-hospitalization or death (10 vs. 7; p=0.74). CONCLUSIONS: Pharmacist intervention significantly reduces the number of patients with clinically relevant DDIs, but not clinical endpoints 6 months from discharge.

Asthma treatment outcome in children is associated with vascular endothelial growth factor A (VEGFA) polymorphisms.

BACKGROUND: Asthma is a common chronic disease characterized by airway inflammation and structural remodeling. Vascular endothelial growth factor (VEGF), a major regulator of angiogenesis, is elevated in asthma patients. VEGF contributes to airway responsiveness and remodeling. It has been shown that treatment of asthma patients decreases VEGF levels, and inhibition of VEGF diminishes asthma symptoms in mice. Therefore, polymorphisms in the vascular endothelial growth factor A (VEGFA) gene might be associated with asthma treatment response. METHODS: This study enrolled 131 children with asthma treated with different therapies - specifically, the inhaled corticosteroid (ICS) fluticasone propionate or the leukotriene receptor antagonist (LTRA) montelukast. We performed an association analysis between improvement of lung function - assessed by measurement of the percentage of the predicted forced expiratory volume in 1 second (%predicted FEV(1)), the ratio between the FEV(1) and the forced vital capacity (FEV(1)/FVC) after 6 and 12 months of treatment, and asthma control after 12 months of treatment - and two polymorphisms, rs2146323 and rs833058, in the VEGFA gene. RESULTS: Polymorphism rs2146323 A>C in VEGFA was associated with response to ICS therapy. Asthma patients with the AA genotype had a greater improvement in the %predicted FEV(1) than those with the AC or CC genotype (p = 0.018). Conversely, the AA genotype in rs2146323 was associated with uncontrolled asthma in patients regularly receiving LTRA therapy (p = 0.020) and a worse FEV(1)/FVC ratio in patients who episodically used LTRA therapy (p = 0.044). Furthermore, polymorphism rs833058 C>T was associated with treatment response to episodically used LTRA therapy. A subgroup of patients with the TT genotype had an improvement in the %predicted FEV(1), compared with no improvement in patients with the CT or CC genotype (p = 0.029). CONCLUSIONS: Our results showed that treatment response to commonly used asthma therapies (ICS or LTRA) is associated with polymorphisms rs2146323 and rs833058 in VEGFA. With additional replication of this preliminary study, our findings could contribute to the development of individualized asthma therapy.

The need for medication reconciliation: a cross-sectional observational study in adult patients.

BACKGROUND: Poor communication of drug therapy at care interface often results in medication errors and adverse drug events. Medication reconciliation has been introduced as a measure to improve continuity of patient care. The aim of this cross-sectional observational study was to evaluate the need for medication reconciliation. METHODS: Comprehensive information on pre-admission therapy was obtained by a research pharmacist for adult medical patients, admitted to a teaching hospital, specialised in pulmonary and allergic diseases, in Slovenia. This information was compared with the in-patient and discharge therapies to identify unintentional discrepancies (medication errors) whose clinical significance was determined by an expert panel reaching consensus. RESULTS: Most of the included 101 patients were elderly (median age: 73 years) who had multiple medications. Among their in-patient drugs (880), few discrepancies were a medication error (54/654), half of which were judged to be clinically important. A higher rate was observed in the discharge drug therapy (747): 369 of the identified discrepancies (566) were a medication error, over half of which were judged as clinically important. A greater number of pre-admission drugs, poorly taken medication histories and a greater number of medication errors in in-patient therapy predisposed patients to clinically important medication errors in discharge therapy. CONCLUSIONS: This study provided evidence in a small sample of patients on the discontinuity of drug therapy at patient discharge in a hospital in Slovenia and its implications for patient care. To ensure continuity and safety of patient care, medication reconciliation should be implemented throughout a patient's hospital stay.

Adherence to treatment guidelines and long-term survival in hospitalized patients with chronic obstructive pulmonary disease.

RATIONALE AND AIMS: Adherence to treatment guidelines in chronic obstructive pulmonary disease (COPD) has been shown to be less than optimal over the COPD continuum. This retrospective study aimed to assess the implementation of COPD guidelines and potential association with long-term mortality in patients with COPD. METHODS: All consecutive patient discharges in the period of February 2002-June 2007 from the University Clinic of Pulmonary and Allergic Diseases Golnik, Slovenia, were screened for a primary discharge diagnosis of COPD. RESULTS: Data on 1185 patients (mean age 70 ± 9 years, 72% men, 64% GOLD stage III/IV) were analysed. In the discharge letters 62% of patients had three or more drugs prescribed; 3% had no regular prescription. Most patients were discharged with short-acting (91%) and long-acting ß2-agonists (LABAs, 65%) and inhaled corticosteroids (61%), and 23% received long-term oxygen therapy. Prescription rates of LABAs, tiotropium and inhaled corticosteroids increased over the disease continuum (P < 0.001). In total, 48% of patients died during a median follow-up of 1149 days. Deceased patients had been less often treated with LABAs, inhaled corticosteroids and tiotropium. In multivariate Cox proportional-hazards analysis, advanced age, current smoking status, lower body mass index, longer hospital stay and cancer were associated with higher mortality (P < 0.05 for all), and inhaled corticosteroids predicted lower mortality (hazard ratio 0.72, 95% confidence interval 0.55-0.94). CONCLUSION: Implementation of guideline-recommended therapy was not optimal, particularly in patients who died during follow-up. The high long-term mortality calls for careful risk assessment and appropriate adherence to treatment guidelines.

Body mass index and prognosis in patients hospitalized with acute exacerbation of chronic obstructive pulmonary disease.

BACKGROUND: Nutritional status, weight loss and cachexia have important prognostic implications in patients with chronic obstructive pulmonary disease (COPD). Body mass index (BMI) has been implicated in COPD risk assessment, but information is mostly limited to composite scores or to patients with stable disease. We aimed to analyse the association between BMI and mortality in acute exacerbation of COPD. METHODS: This retrospective survey included 968 patients hospitalized due to acute exacerbation of COPD at the University Clinic Golnik from February 2002 to June 2007. Vital status was ascertained with Central Population Registry, and database was censored on November 1, 2008. RESULTS: Median BMI was 25.08 kg/m(2) (interquartile range, 21.55-29.05 kg/m(2)) and 210 patients (22%) had BMI < 21 kg/m(2). During median follow-up of 3.26 years (1.79-4.76 years), 430 patients (44%) died. Lowest mortality was found for BMI 25.09-29.05 kg/m(2). When divided per BMI decile, mortality was lowest for BMI 25.09-26.56 kg/m(2) (33%). In univariate analysis, BMI per quartile and BMI per unit increase were predictive for all-cause mortality. In an adjusted model, BMI per 1 kg/m(2) unit increase was associated with 5% less chance of death (hazard ratio 0.95, 95% confidence interval 0.93-0.97). CONCLUSIONS: Low BMI < 21 kg/m(2) is frequent in patients hospitalized due to acute exacerbation of COPD. Higher BMI was independently predictive of better long-term survival. A better outcome in obese patients compared to normal weight is in contrast to primary prevention data but concurs with observations of an obesity paradox in other cardiovascular diseases.

Heart failure and chronic obstructive pulmonary disease: Two for tea or tea for two?

A combination of chronic obstructive pulmonary disease (COPD) and heart failure (HF) is common yet it is inadequately and rarely recognized. Because of the similar clinical manifestations, comorbidity is frequently not considered and appropriate diagnostic tests are not performed. It is very important that a combination of COPD and HF is recognized as these patients have a worse prognosis than patients with an individual disease. When present, COPD should not prevent the use of life-saving therapy in patients with HF, particularly ß-blockers. Despite clear evidence of the safety and tolerability of cardioselective ß-blockers in COPD patients, these drugs remain grossly underprescribed and underdosed. Routine spirometry and echocardiography in HF and COPD patients, respectively, is therefore warranted to improve current clinical practice.

Self-rated health predicts acute exacerbations and hospitalizations in patients with COPD.

BACKGROUND: Self-rated health predicts outcome in chronic disease, but such information is scarce in COPD. We aimed to assess self-rated health as an outcome predictor in carefully characterized patients with this condition. METHODS: This was a prospective study in 127 clinically stable patients with COPD (64 +/- 8 years, 79% men, 82% Global Initiative for Chronic Obstructive Lung Disease stage II or III). Self-rated health was assessed using a 5-grade Likert scale ranging from very poor to very good. RESULTS: During 26.0 +/- 4.9 months of follow-up, 78 patients experienced acute exacerbation, 39 were hospitalized, and 10 died. Poor or very poor self-rated health was reported by 19 patients (15%) and was more common in patients experiencing acute exacerbations (20% vs 6%, P = .027) and hospitalizations (19% vs 5%, P = .039). Kaplan-Meier curves demonstrated more acute exacerbations (P = .003) and hospitalizations (P = .008) in patients with poor or very poor self-rated health. In a fully adjusted Cox model of proportional hazard, poor or very poor self-rated health remained predictive of acute exacerbations (hazard ratio [HR], 1.80; 95% CI, 1.03-3.11) and hospitalizations (HR, 1.93; 95% CI, 1.12-3.68) but not of death. CONCLUSIONS: This study suggests that self-rated health is predictive of acute exacerbations and hospitalizations. Although prediction of mortality was limited, the study is supportive of self-rated health testing in COPD.

Complement factors c3a, c4a, and c5a in chronic obstructive pulmonary disease and asthma.

Studies of animal models have shown that the activation of the complement system could have a role in chronic obstructive pulmonary disease (COPD) and asthma by promoting inflammation and enhancing airway hyperresponsiveness. We sought to determine whether the levels of complement factors C3a, C4a, and C5a are elevated at the site of inflammation in patients with COPD and patients with asthma. We analyzed the induced sputum of seven patients with COPD, ten patients with asthma, and twelve healthy nonsmokers. The concentrations of anaphylatoxins in the induced sputum were measured by cytometric bead array. We found significantly increased C5a/C5a desArg concentrations in supernatants of the induced sputum of patients with COPD (P = 0.007) and those with asthma (P = 0.002) compared with the control group. In patients with COPD the C5a/C5a desArg concentrations were significantly negatively correlated with lung diffusion coefficient (r = -0.71, P = 0.035). There was no significant difference in C3a/C3a desArg or C4a/C4a desArg measurements between the three groups of subjects. These in vivo results propose the involvement of complement factor C5a in the pathogenesis of COPD and asthma.