Catherina L Chang

Biochemical markers of cardiac dysfunction predict mortality in acute exacerbations of COPD

Background Retrospective studies suggest that plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac troponin T are often elevated in patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) and are associated with increased mortality. These cardiac biomarkers were investigated in an unselected cohort of patients admitted to hospital with exacerbations of COPD. Methods Consecutive patients with physician-diagnosed COPD exacerbation but without clinical evidence of acute cardiac disease admitted to a public hospital over a 1 year period were studied prospectively. NT-proBNP and troponin T were measured on admission. The primary end point was all-cause mortality at 30 days. Results Elevated NT-proBNP (>220 pmol/l) was present in 65/244 patients (27.5%) and significantly predicted 30-day mortality (OR 9.0, 95% CI 3.1 to 26.2, p<0.001). Elevated troponin T (>0.03 μg/l) was found in 40/241 patients (16.6%) and also predicted 30-day mortality (OR 6.3, 95% CI 2.4 to 16.5, p<0.001). These associations persisted after adjusting for other clinical and laboratory predictors of mortality (arterial CO2 pressure (Paco2), body mass index and CURB65 score). NT-proBNP and troponin T levels appeared to have additive associations with mortality: 30-day mortality among patients with abnormalities of both NT-proBNP and troponin T was 15-fold higher than among patients with normal values. Conclusion Elevated levels of NT-proBNP and troponin T are strong predictors of early mortality among patients admitted to hospital with acute exacerbations of COPD independently of other known prognostic indicators. The pathophysiological basis for this is unknown, but indicates that cardiac involvement in exacerbations of COPD may be an important determinant of prognosis.

Glycopyrronium once-daily significantly improves lung function and health status when combined with salmeterol/fluticasone in patients with COPD: the GLISTEN study—a randomised controlled trial

Background The optimal use of various therapeutic combinations for moderate/severe chronic obstructive pulmonary disease (COPD) is unclear. The GLISTEN trial compared the efficacy of two long-acting anti-muscarinic antagonists (LAMA), when combined with an inhaled corticosteroid (ICS) and a long-acting β2 agonist (LABA). Methods This randomised, blinded, placebo-controlled trial in moderate/severe COPD patients compared once-daily glycopyrronium (GLY) 50 µg, once-daily tiotropium (TIO) 18 µg or placebo (PLA), when combined with salmeterol/fluticasone propionate (SAL/FP) 50/500 µg twice daily. The primary objective was to determine the non-inferiority of GLY+SAL/FP versus TIO+SAL/FP on trough FEV1 after 12 weeks. An important secondary objective was whether addition of GLY to SAL/FP was better than SAL/FP alone. Results 773 patients (mean FEV1 57.2% predicted) were randomised; 84.9% completed the trial. At week 12, GLY+SAL/FP demonstrated non-inferiority to TIO+SAL/FP for trough FEV1: least square mean treatment difference (LSMdiff) −7 mL (SE 17.4) with a lower limit for non-inferiority of −60 mL. There was significant increase in week 12 trough FEV1 with GLY+SAL/FP versus PLA+SAL/FP (LSMdiff 101 mL, p<0.001). At 12 weeks, GLY+SAL/FP produced significant improvement in St Georges Respiratory Questionnaire total score versus PLA+SAL/FP (LSMdiff −2.154, p=0.02). GLY+SAL/FP demonstrated significant rescue medication reduction versus PLA+SAL/FP (LSMdiff −0.72 puffs/day, p<0.001). Serious adverse events were similar for GLY+SAL/FP, TIO+SAL/FP and PLA+SAL/FP with an incidence of 5.8%, 8.5% and 5.8%, respectively. Conclusions GLY+SAL/FP showed comparable improvements in lung function, health status and rescue medication to TIO+SAL/FP. Importantly, addition of GLY to SAL/FP demonstrated significant improvements in lung function, health status and rescue medication compared to SAL/FP. Trial registration number NCT01513460.

Predicting early mortality in acute exacerbation of chronic obstructive pulmonary disease using the CURB65 score.

Background and Objective:  Hospitalization for exacerbation of COPD is associated with a high risk of mortality. A risk‐prediction model using information easily obtained on admission could help to identify high‐risk individuals. The CURB65 score was developed to predict mortality risk in community acquired pneumonia. A retrospective study found that this score was also associated with mortality in COPD exacerbations. We conducted a prospective study to assess the utility of the CURB65 score in acute COPD exacerbations.

Audit of acute admissions of chronic obstructive pulmonary disease: inpatient management and outcome

Background: Despite the publication of several management guidelines for exacerbations of chronic obstructive pulmonary disease (COPD), there is little information on standards of care in clinical practice. The aim of this audit was to examine the assessment, management and outcome of COPD admissions to a secondary and tertiary referring New Zealand hospital during two different seasons. Compliance to current recommendations was examined and compared with the available international published work.

Cardiac dysfunction during exacerbations of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) and cardiovascular disease often coexist, and acute cardiac events frequently occur during COPD exacerbations. Even when cardiac complications are not clinically apparent, biochemical evidence of cardiac dysfunction is often noted during exacerbations and portends poor prognosis. Diagnosis of cardiac disease in COPD can be difficult and necessitates a high degree of clinical suspicion. However, the additional strain of an exacerbation could be a pivotal moment, during which previously unsuspected cardiac dysfunction is exposed. In this Review, we present evidence about cardiac involvement in exacerbations of COPD, and discuss diagnostic challenges and treatment opportunities.

Sensitivity and specificity of the Geriatric Anxiety Inventory and the Hospital Anxiety and Depression Scale in the detection of anxiety disorders in older people with chronic obstructive pulmonary disease.

BACKGROUND Anxiety and depression are prevalent in patients with chronic obstructive pulmonary disease (COPD). This study evaluates the sensitivity and specificity of two self-administered anxiety rating scales in older people with COPD. The Geriatric Anxiety Inventory (GAI) and the Hospital Anxiety and Depression Scale (HADS) are established useful screening tools but they have not been previously validated in this population. METHODS Older people with COPD completed the GAI and the HADS along with a structured diagnostic psychiatric interview, the Mini International Neuropsychiatric Interview (MINI). The outcomes of both rating scales were compared against the diagnosis of anxiety disorders based on the MINI. Receiver operating characteristic (ROC) curves were used to identify the optimal diagnostic cut points for each scale. RESULTS Fourteen (25.5%) of the 55 participants, were diagnosed with an anxiety disorder. Mean GAI and HADS-anxiety subscale scores were significantly higher in subjects with an anxiety disorder than those without the diagnosis (p = 0.002 and 0.005 respectively). Both scales demonstrated moderate diagnostic value (area under the ROC curve was 0.83 for GAI and 0.79 for HADS). Optimal cut points were ≥3 (GAI) and ≥4 (HADS-anxiety subscale). At these cut-points, the GAI had a sensitivity of 85.7%, specificity of 78.0% and the HADS had a sensitivity of 78.6%, specificity 70.7%. CONCLUSION Our results support the use of the GAI and HADS as screening instruments for anxiety disorders in older people with COPD. The optimal cut points in this population were lower than previously recommended for both rating scales. The results of this study should be replicated before these cut points can be recommended for general use in older people with COPD.

Biomarkers of cardiac dysfunction and mortality from community-acquired pneumonia in adults.

Background Cardiac dysfunction is common in acute respiratory diseases and may influence prognosis. We hypothesised that blood levels of N-terminal B-type natriuretic peptide (NT-proBNP) and high-sensitivity Troponin T would predict mortality in adults with community-acquired pneumonia. Methods and Findings A prospective cohort of 474 consecutive patients admitted with community-acquired pneumonia to two New Zealand hospitals over one year. Blood taken on admission was available for 453 patients and was analysed for NT-proBNP and Troponin T. Elevated levels of NT-proBNP (>220 pmol/L) were present in 148 (33%) and 86 (19%) of these patients respectively. Among the 26 patients who died within 30 days of admission, 23 (89%) had a raised NT-proBNP and 14 (53%) had a raised Troponin T level on admission compared to 125 (29%) and 72 (17%) of the 427 who survived (p values<0.001). Both NT-proBNP and Troponin T predicted 30-day mortality in age-adjusted analysis but after mutual adjustment for the other cardiac biomarker and the Pneumonia Severity Index, a raised N-terminal pro-brain natriuretic peptide remained a predictor of 30-day mortality (OR = 5.3, 95% CI 1.4–19.8, p = 0.013) but Troponin T did not (OR = 1.3, 95% CI 0.5–3.2, p = 0.630). The areas under the receiver-operating curves to predict 30-day mortality were similar for NT-proBNP (0.88) and the Pneumonia Severity Index (0.87). Conclusions Elevated N-terminal B-type natriuretic peptide is a strong predictor of mortality from community-acquired pneumonia independent of clinical prognostic indicators. The pathophysiological basis for this is unknown but suggests that cardiac involvement may be an under-recognised determinant of outcome in pneumonia and may require a different approach to treatment. In the meantime, measurement of B-type natriuretic peptides may help to assess prognosis.

Cardio‐selective and non‐selective beta‐blockers in chronic obstructive pulmonary disease: effects on bronchodilator response and exercise

Background: Patients with chronic obstructive pulmonary disease (COPD) often have co‐existing cardiovascular disease and may require beta‐blocker treatment. There are limited data on the effects of beta‐blockers on the response to inhaled β2‐agonists and exercise capacity in patients with COPD.

Modafinil improves daytime sleepiness in patients with mild to moderate obstructive sleep apnoea not using standard treatments: a randomised placebo-controlled crossover trial

Introduction Patients with mild to moderate obstructive sleep apnoea (OSA) commonly suffer excessive daytime sleepiness. Continuous positive airway pressure (CPAP) has limited effectiveness in reducing sleepiness in milder OSA. Modafinil is a wake-promoting drug licensed to treat residual sleepiness in CPAP-treated OSA. We hypothesised that modafinil may effectively treat sleepiness in untreated mild to moderate OSA. Methods Untreated sleepy men with mild to moderate OSA (age 18–70, apnoea-hypopnoea index (AHI) 5–30/h, Epworth Sleepiness Scale (ESS) ≥10) were randomised to receive 200 mg modafinil or matching placebo daily for 2 weeks before crossing over to the alternative treatment after a minimum 2-week washout. Mixed model analysis of variance was used to compare the changes on modafinil to placebo while classifying all randomised patients as random factors. Results 32 patients were randomised (mean (SD) AHI 13 (6.4)/h, age 47 (10.7) years, ESS 13.6 (3.3), body mass index 28.2 (3.6) kg/m2), 29 of whom (91%) completed the trial. The primary outcome (ESS) improved more on modafinil than placebo (3.6 points, 95% CI 1.3 to 5.8, p=0.003) and the secondary outcome (40-min driving simulator performance) also improved more on modafinil than placebo (steering deviation 4.7 cm, 95% CI 0.8 to 8.5, p=0.018). Psychomotor Vigilance Task reciprocal reaction time improved significantly over placebo (0.15 (1/ms), 95% CI 0.03 to 0.27, p=0.016). Improvements on the Functional Outcomes of Sleep Questionnaire were not significant (5.3 points over placebo, 95% CI −1 to 11.6, p=0.093). Conclusions Modafinil significantly improved subjective sleepiness in patients with untreated mild to moderate OSA. The size of this effect is clinically relevant at 3–4 ESS points of improvement compared with only 1–2 points in CPAP clinical trials. Driving simulator performance and reaction time also improved on modafinil. Clinical Trial Registration ACTRN#12608000128392.

Cardiac dysfunction and N-terminal pro-B-type natriuretic peptide in exacerbations of chronic obstructive pulmonary disease

Elevated levels of B‐type natriuretic peptides among patients with exacerbations of chronic obstructive pulmonary disease (COPD) are associated with higher mortality. The pathophysiology is unclear. To establish if elevated levels of N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) are due to right or left heart dysfunction, we performed echocardiograms in 18 patients admitted to hospital with COPD. Elevated levels of NT‐proBNP were associated with both right and left heart dysfunction and indicate that these patients have biventricular dysfunction rather than isolated right ventricular compromise.