Impact of COVID-19 pandemic restrictions on the cardio-respiratory health of New Zealanders.

BACKGROUND AND OBJECTIVE: The COVID-19 pandemic has caused disruption to health, social interaction, travel and economies worldwide. In New Zealand, the government closed the border to non-residents and required all arrivals to quarantine for 14 days. They also implemented a strict contact-restriction system to eliminate COVID-19 from the community. These measures also reduced the circulation of other respiratory viruses such as influenza and respiratory syncytial virus. We assessed the impact of these measures on hospital admissions for respiratory and cardiac diseases. METHODS: National data on hospital admissions for each week of 2020 were compared to admissions for the previous 5 years. Analyses were curtailed after week 33, when a COVID-19 outbreak in Auckland led to different levels of pandemic restrictions making national data difficult to interpret. RESULTS: The numbers of acute infectious respiratory admissions were similar to previous years before the introduction of COVID-19 restrictions, but then fell lower and remained low after the pandemic restrictions were eased. The usual winter peak in respiratory admissions was not seen in 2020. Other than small reductions during the period of the strictest contact restrictions, non-infectious respiratory and cardiac admissions were similar to previous years and the usual winter peak in heart failure admissions was observed. CONCLUSION: The observed patterns of hospital admissions in 2020 are compatible with the hypothesis that circulating respiratory viruses drive the normal seasonal trends in respiratory admissions. By contrast, these findings suggest that respiratory viruses do not drive the winter peak in heart failure.

Cardiac dysfunction in exacerbations of chronic obstructive pulmonary disease is often not detected by electrocardiogram and chest radiographs.

BACKGROUND: Cardiac dysfunction is common in exacerbations of chronic obstructive pulmonary disease (COPD), even in patients without clinically suspected cardiac disorders. AIM: To investigate associations between electrocardiogram (ECG) and chest radiograph abnormalities and biochemical evidence of cardiac dysfunction (N-terminal pro-B-type natriuretic peptide and troponin T) in patients hospitalised with exacerbations of COPD at Waikato Hospital. METHODS: Independent examiners, blinded to NT-proBNP and troponin T levels, assessed ECG for tachycardia, atrial fibrillation, ventricular hypertrophy and ischaemic changes in 389 patients and chest radiographs for signs of heart failure in 350 patients. Associations between electrocardiographic and radiographic abnormalities with at least moderate interrater agreement and cardiac biomarkers were analysed. RESULTS: High NT-proBNP values (>220 pmol/L) were associated with atrial fibrillation (22 vs 6%), right ventricular hypertrophy (24 vs 15%), left ventricular hypertrophy (15 vs 4%), ischaemia (59 vs 33%) and cardiomegaly (42 vs 20%). High troponin T values (>0.03ug/L or high-sensitivity >50 ng/L) were associated with tachycardia (65 vs 41%), right ventricular hypertrophy (26 vs 15%) and ischaemia (60 vs 36%). None of the electrocardiographic or radiographic abnormalities was sensitive or specific for cardiac biomarker abnormalities. Ischaemia on ECG was the best indicator for raised NT-proBNP (sensitivity 59%, specificity 67%). Tachycardia and ischaemia were the best indicators of raised troponin T (sensitivity 65 and 60%, specificity 59 and 64% respectively). CONCLUSIONS: ECG and chest radiograph abnormalities have poor sensitivity and specificity for diagnosing acute cardiac dysfunction in exacerbations of COPD. Cardiac biomarkers provide additional diagnostic information about acute cardiac dysfunction in exacerbations of COPD.

A double-blind, randomised, placebo-controlled study of roxithromycin and doxycycline combination, roxithromycin alone, or matching placebo for 12 weeks in adults with frequent exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Azithromycin prophylaxis has been shown to reduce COPD exacerbations but there is poor evidence for other antibiotics. We compared exacerbation rates in COPD patients with a history of frequent exacerbations (at least three moderate or severe COPD exacerbations in the past two years) during a 12-week treatment course and over a subsequent 48-week follow up period. RESULTS: 292 patients were randomised to one of three treatments for 12 weeks: roxithromycin 300 mg daily and doxycycline 100 mg daily (n = 101); roxithromycin 300 mg daily (n = 97); or matching placebos (n = 94). There were no differences in the annualised moderate and severe exacerbation rates after treatment with roxithromycin/doxycycline (2.83 (95 % CI 2.37-3.40)) or roxithromycin only (2.69 (2.26-3.21)) compared to placebo (2.5 (2.08-3.03)) (p = 0.352 and p = 0.5832 respectively). Furthermore, there were no differences in the annualised exacerbation rates during 12-week treatment with roxithromycin/doxycycline (1.64 (95 % CI 1.17-2.30)), roxithromycin only (1.75 (1.24-2.41)) or placebo (2.23 (1.68-3.03)) (p = 0.1709 and p = 0.2545 respectively). There were also no significant differences between groups for spirometry or quality of life scores over either the 12-week treatment or 48-week post-treatment periods. Both active treatments were associated with nausea but otherwise adverse events were comparable among treatment groups. CONCLUSIONS: Twelve-weeks of prophylaxis with roxithromycin/doxycycline combination or roxithromycin alone did not reduce COPD exacerbations in patients with history of frequent exacerbations. These findings do not support the use of these antibiotics to prevent exacerbations in COPD patients.

Global mortality and readmission rates following COPD exacerbation-related hospitalisation: a meta-analysis of 65 945 individual patients.

Background: Exacerbations of COPD (ECOPD) have a major impact on patients and healthcare systems across the world. Precise estimates of the global burden of ECOPD on mortality and hospital readmission are needed to inform policy makers and aid preventive strategies to mitigate this burden. The aims of the present study were to explore global in-hospital mortality, post-discharge mortality and hospital readmission rates after ECOPD-related hospitalisation using an individual patient data meta-analysis (IPDMA) design. Methods: A systematic review was performed identifying studies that reported in-hospital mortality, post-discharge mortality and hospital readmission rates following ECOPD-related hospitalisation. Data analyses were conducted using a one-stage random-effects meta-analysis model. This study was conducted and reported in accordance with the PRISMA-IPD statement. Results: Data of 65 945 individual patients with COPD were analysed. The pooled in-hospital mortality rate was 6.2%, pooled 30-, 90- and 365-day post-discharge mortality rates were 1.8%, 5.5% and 10.9%, respectively, and pooled 30-, 90- and 365-day hospital readmission rates were 7.1%, 12.6% and 32.1%, respectively, with noticeable variability between studies and countries. Strongest predictors of mortality and hospital readmission included noninvasive mechanical ventilation and a history of two or more ECOPD-related hospitalisations <12 months prior to the index event. Conclusions: This IPDMA stresses the poor outcomes and high heterogeneity of ECOPD-related hospitalisation across the world. Whilst global standardisation of the management and follow-up of ECOPD-related hospitalisation should be at the heart of future implementation research, policy makers should focus on reimbursing evidence-based therapies that decrease (recurrent) ECOPD.

A case report describing the use of systemic bevacizumab in the treatment of recurrent respiratory papillomatosis with pulmonary involvement.

Recurrent respiratory papillomatosis (RRP) is a rare disease characterized by recurrent papilloma along the aerodigestive tract. In this case, we describe a 16-year-old with longstanding laryngeal RRP secondary to vertical transmission of human papillomavirus (HPV) who presented with symptomatic pulmonary involvement and was successfully treated with systemic bevacizumab. The case describes the clinical and radiological improvement with therapy as well as the adverse effects that occurred and resolved with dose adjustments.

Cardiac biomarkers and long-term outcomes of exacerbations of COPD: a long-term follow-up of two cohorts.

BACKGROUND: COPD patients often have cardiac comorbidities. Cardiac involvement at the time of a COPD exacerbation is associated with a high short-term mortality, but whether this influences long-term outcomes is unknown. We explored whether biomarkers of cardiac dysfunction at the time of a COPD exacerbation predict long-term outcomes. METHODS: Two prospective cohorts of patients admitted to Waikato Hospital for exacerbations of COPD were recruited during 2006-2007 and 2012-2013. N-terminal pro-B-type natriuretic peptide (NT-proBNP) and troponin T were measured on admission and were used to indicate cardiac stretch and myocardial injury, respectively. 5-year survival after discharge and subsequent admissions for cardiac disease and COPD exacerbations were analysed using Kaplan-Meier and Cox proportional hazards tests. RESULTS: The overall 5-year mortality was 61%. Patients with high NT-proBNP on admission had higher mortality than those with normal cardiac biomarkers (adjusted hazard ratio (aHR) 1.76, 95% CI 1.18-2.62). High NT-proBNP was also associated with a higher risk of future cardiac admissions (aHR 1.75, 95% CI 1.2-2.55). Troponin T levels were not associated with long-term survival (aHR 0.86, 95% CI 0.40-1.83) or future cardiac admissions (aHR 0.74, 95% CI 0.34-1.57). Neither biomarker predicted future COPD exacerbations. CONCLUSION: The long-term prognosis following a hospitalisation for an exacerbation of COPD is poor with less than half of patients surviving for 5 years. Elevated NT-proBNP at the time of a COPD exacerbation is associated with higher long-term mortality and a greater likelihood of future cardiac admissions, but not future COPD exacerbations.

MULTI-PHACET: multidimensional clinical phenotyping of hospitalised acute COPD exacerbations.

BACKGROUND: The generic term "exacerbation" does not reflect the heterogeneity of acute exacerbations of COPD (AECOPD). We utilised a novel algorithmic strategy to profile exacerbation phenotypes based on underlying aetiologies. METHODS: Patients hospitalised for AECOPD (n=146) were investigated for aetiological contributors summarised in a mnemonic acronym ABCDEFGX (A: airway virus; B: bacterial; C: co-infection; D: depression/anxiety; E: eosinophils; F: failure (cardiac); G: general environment; X: unknown). Results from clinical investigations were combined to construct AECOPD phenotypes. Relationships to clinical outcomes were examined for both composite phenotypes and their specific aetiological components. Aetiologies identified at exacerbation were reassessed at outpatient follow-up. RESULTS: Hospitalised AECOPDs were remarkably diverse, with 26 distinct phenotypes identified. Multiple aetiologies were common (70%) and unidentifiable aetiology rare (4.1%). If viruses were detected (29.5%), patients had longer hospitalisation (7.7±5.6 versus 6.0±3.9 days, p=0.03) despite fewer "frequent exacerbators" (9.3% versus 37%, p=0.001) and lower mortality at 1 year (p=0.03). If bacterial infection was found (40.4%), patients were commonly "frequent exacerbators" (44% versus 18.4%, p=0.001). Eosinophilic exacerbations (28%) were associated with lower pH (7.32±0.06 versus 7.36±0.09, p=0.04), higher venous carbon dioxide tension (P vCO2 ) (53.7±10.5 versus 48.8±12.8, p=0.04), greater noninvasive ventilation (NIV) usage (34.1% versus 18.1%) but shorter hospitalisation (4 (3-5) versus 6 (4-9) days, p<0.001) and lower infection rates (41.4% versus 80.9%, p<0.0001). Cardiac dysfunction and severe anxiety/depression were common in both infective and non-infective exacerbations. Characteristics identified at exacerbation often persisted after recovery. CONCLUSIONS: Hospitalised AECOPDs have numerous causes, often in combination, that converge in complex, multi-faceted phenotypes. Clinically important differences in outcomes suggest that a phenotyping strategy based on aetiologies can enhance AECOPD management.

Comparing severity scores in exacerbations of chronic obstructive pulmonary disease.

INTRODUCTION: Prognostic scores help identify patients at a high risk of mortality in exacerbations of chronic obstructive pulmonary disease (COPD). The Dyspnoea, Eosinopaenia, Consolidation, Acidaemia and atrial Fibrillation (DECAF) score has been reported to perform better than other severity scores in predicting mortality from exacerbations of COPD in studies including patients with pneumonia. OBJECTIVE: To compare the performance of DECAF with other prognostic scores: CURB-65, CRB-65 and BAP-65, in predicting 30-day mortality in patients hospitalised with exacerbations of COPD without pneumonia. METHODS: Data from hospital admission of 423 patients from two cohorts of patients with exacerbations of COPD without consolidation on chest radiographs were used to compile the CURB-65, CRB-65, BAP-65 and DECAF scores. The performance of each prognostic score in predicting 30-day mortality was studied using receiver operating curve analysis. RESULTS: Thirty-one patients (7%) died within 30 days of hospital admission. One hundred patients (24%) did not have DECAF scores because of the incomplete laboratory data, while all 423 patients had the other scores available for analysis. All scores predicted mortality with similar areas under the receiver operating characteristic curve (CURB-65 = 0.69, CRB-65 = 0.64, BAP-65 = 0.64, DECAF = 0.65, P = 0.186). CONCLUSION: In patients hospitalised with exacerbations of COPD without pneumonia, simple clinical scores that rely on fewer laboratory measures perform at least as well as DECAF in predicting early mortality.

Changes in biomarkers of cardiac dysfunction during exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Cardiac dysfunction is associated with a higher mortality in exacerbations of chronic obstructive pulmonary disease (COPD). It is unknown how the heart responds to treatment of COPD exacerbations. We followed cardiac biomarker levels during hospital admissions for exacerbations of COPD and hypothesised that these biochemical markers of cardiac dysfunction might be affected the severity and treatment of exacerbations of COPD. METHODS: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and troponin T were measured at admission, 12 h, 72 h, and clinical stability in 176 patients. In a second cohort (n = 93), associations between blood salbutamol concentrations and biomarker changes at 12 h were analysed. RESULTS: NT-proBNP increased from a geometric mean of 43 pmol/L at admission to 56 pmol/L at 12 h (p < 0.001), 53 pmol/L at 72 h (p = 0.045), and decreased to 25 pmol/L (p < 0.001) at stability. Troponin T levels decreased at 12 h (p < 0.001), but 15/174 (9%) patients had a clinically significant rise. Nebulised bronchodilator treatment and blood salbutamol concentrations were associated with greater increases in NT-proBNP rise at 12 h independently of baseline COPD or exacerbation severity and other treatments (p < 0.05). Nebulised bronchodilator and blood salbutamol concentrations also predicted rises in troponin T in univariate analyses (p < 0.05). CONCLUSIONS: NT-proBNP continues to rise after admission to hospital for COPD exacerbations and a minority of patients have clinically significant rises in cardiac troponins. These rises were associated with nebulised beta2-agonist treatment. These findings suggest that high doses of beta2-agonists may exacerbate cardiac dysfunction in COPD.

ß-blockers in exacerbations of COPD: feasibility of a randomised controlled trial.

A feasibility randomised controlled trial of ß-blockers in acute exacerbations of COPD http://ow.ly/lVcy305B36D.

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.