Nutritional support and functional capacity in chronic obstructive pulmonary disease: A systematic review and meta‐analysis

Currently, there is confusion about the value of using nutritional support to treat malnutrition and improve functional outcomes in chronic obstructive pulmonary disease (COPD). This systematic review and meta‐analysis of randomized, controlled trials (RCT) aimed to clarify the effectiveness of nutritional support in improving functional outcomes in COPD. A systematic review identified 12 RCT (n = 448) in stable COPD patients investigating the effects of nutritional support (dietary advice (1 RCT), oral nutritional supplements (10 RCT), enteral tube feeding (1 RCT)) versus control on functional outcomes. Meta‐analysis of the changes induced by intervention found that while respiratory function (forced expiratory volume in 1 s, lung capacity, blood gases) was unresponsive to nutritional support, both inspiratory and expiratory muscle strength (maximal inspiratory mouth pressure +3.86 standard error (SE) 1.89 cm H₂O, P = 0.041; maximal expiratory mouth pressure +11.85 SE 5.54 cm H₂O, P = 0.032) and handgrip strength (+1.35 SE 0.69 kg, P = 0.05) were significantly improved and associated with weight gains of ≥2 kg. Nutritional support produced significant improvements in quality of life in some trials, although meta‐analysis was not possible. It also led to improved exercise performance and enhancement of exercise rehabilitation programmes. This systematic review and meta‐analysis demonstrates that nutritional support in COPD results in significant improvements in a number of clinically relevant functional outcomes, complementing a previous review showing improvements in nutritional intake and weight.     

Longitudinal follow up of elevated pulmonary artery pressures in children with sickle cell disease

Elevated pulmonary artery pressures (PAP) occur in approximately 30% of children with sickle cell disease. In adults, pulmonary hypertension is significantly associated with mortality. There are no data on the long term significance in children. Nineteen children with SS/Sß⁰ thalassaemia had elevated PAP, defined as tricuspid regurgitant jet velocity (TRV) ≥2·5 m/s on screening echocardiograms. They were prospectively followed for 23 months (range 19–31 months). Patients with initial TRV ≥ 3 or TRV ≥ 2·5 m/s on repeat echocardiogram had cardiopulmonary evaluation and were offered treatment with hydroxyurea. Associated conditions like asthma and obstructive sleep apnea were treated. 18/19 patients had follow-up echocardiograms. These showed normalization of TRV in 8 patients. Risk factors associated with persistent elevation were higher TRV on initial echocardiogram ( P  = 0·01), lower haemoglobin ( P  = 0·003) and lower oxygen saturation ( P  = 0·03). Five patients with persistently elevated PAP were treated with hydroxyurea. Mean right ventricular pressure dropped from 40·16 to 29·26 ( P  = 0·017) after 3–6 months and to 23·6 mmHg ( P  = 0·002) after 9–12 months on treatment. In conclusion (i) At borderline elevation of TRV there is intrapatient variability and echocardiograms should be repeated for confirmation. (ii) Elevated PAP are reversible in children with early detection and treatment with hydroxyurea.     

Benefit and risk of adding rivaroxaban in patients with coronary artery disease: A systematic review and meta‐analysis

BackgroundAlthough the European Medicines Agency and the US Food and Drug Administration have, respectively, approved rivaroxaban for the prevention of recurrent major adverse cardiovascular events in patients with myocardial infarction and stable coronary artery disease, its efficacy and safety is unclear. This meta‐analysis aimed to evaluate the benefit and risk of adding rivaroxaban in coronary artery disease (CAD) patients, focusing on treatment effects stratified by different baseline clinical presentations.HypothesisThere are differences in treatment effects of adding rivaroxaban among CAD patients with different baseline clinical presentations.MethodsMedline, EMBASE, and Cochrane Databases were systematically searched from inception to 21 July 2020 for randomized controlled trials (RCTs) comparing rivaroxaban in CAD patients. The primary efficacy endpoint and safety endpoint were assessed by using Mantel–Haenszel pooled risk ratios (RRs) and 95% confidence intervals (CIs).ResultsFive RCTs that included 43 650 patients were identified. Patients receiving rivaroxaban had a significantly lower risk of the primary efficacy endpoint (RR, 0.86; 95% CI, 0.76–0.97, p = .01) accompanied by increased risk of the primary safety endpoint (RR, 1.83; 95% CI, 1.10–3.05, p = .02). Subgroup analyses showed that in males the risk–benefit appears to be more favorable while in patients ≥65 years, in females, in patients with diabetes, those with mild to moderate impaired renal function, and region of Asia/other seems unfavorable.ConclusionRivaroxaban may provide an additional choice for secondary prevention in CAD patients. However, careful estimation of the risk of ischemic and bleeding events using patient characteristics are critical to achieving net benefit.     

Glucocorticoid‐induced hyperglycaemia in respiratory disease: a systematic review and meta‐analysis

The relative risk of glucocorticoid‐induced hyperglycaemia is poorly quantified. We undertook a meta‐analysis to estimate the association between glucocorticoid treatment and hyperglycaemia, overall and separately in individuals with and without diabetes and underlying respiratory disease. We searched electronic databases for clinical trials of adults randomized to either glucocorticoid treatment or placebo. Eight articles comprising 2121 participants were identified. We performed a random effects meta‐analysis to determine relative risks for the associations between glucocorticoid use and both hyperglycaemia and starting hypoglycaemic therapy. In all individuals, the relative risk of hyperglycaemia comparing glucocorticoid treatment with placebo was 1.72 [95% confidence interval (CI) 1.50‐2.04; p < .001]. The relative risks in individuals with and those without diabetes were 2.10 (95% CI 0.92‐5.02; p = .079) and 1.50 (95% CI 0.79‐2.86; p = .22), respectively. In all individuals, the relative risk of hyperglycaemia requiring initiation of hypoglycaemic therapy, comparing glucocorticoid treatment with placebo, was 1.73 (95% CI 1.40‐2.14; p < .001). In conclusion, glucocorticoid therapy increases the risk of hyperglycaemia in all individuals with underlying respiratory disease but not when diabetic status is analysed separately.     

Endothelin receptor antagonists for pulmonary hypertension in adult patients with sickle cell disease

Pulmonary Hypertension is a serious complication of sickle cell disease (SCD), with high morbidity and mortality. Endothelin (ET)-1, a potent vasoconstrictor elevated in SCD, acts through the ET receptors (ETR), ETR-A and ETR-B. Bosentan and ambrisentan are ETR blockers used in primary pulmonary hypertension. We report on the use of ETR blocking agents in a cohort of 14 high-risk SCD adult patients with pulmonary hypertension. Patients underwent right heart catheterization, 6-min walk test, echocardiogram, physical examination and blood work-up before starting ETR blockers. Eight patients received ETR blockers as initial therapy; six patients were already taking sildenafil. Over more than 6 months of therapy, sequential measurements of 6-min walk distance increased significantly (baseline 357 ± 22 to 398 ± 18 m at 5–6 months, P  < 0·05). Downward trends were observed for amino-terminal brain natriuretic peptide and tricuspid regurgitant velocity. Pulmonary artery mean pressures decreased in three patients that had repeat right heart catheterization (44–38 mmHg). Adverse events were: increased serum alanine aminotransferase (2), peripheral oedema (4), rash (1), headache (3), decreased haemoglobin (2). Therapy was stopped in two patients who were switched then to the other ETR blocker agent. These data suggest preliminary evidence for the benefit of bosentan and ambrisentan in pulmonary hypertension in SCD.     

Chronic sickle cell lung disease: new insights into the diagnosis, pathogenesis and treatment of pulmonary hypertension

Pulmonary hypertension is a common complication of sickle cell disease (SCD). In spite of the mild elevations in pulmonary artery pressures in these patients, the associated morbidity and mortality is high. In fact, in adult patients with SCD, pulmonary hypertension is emerging as the major independent risk factor for death. The aetiology of pulmonary hypertension is probably multifactorial, including haemolysis, impaired nitric oxide bioavailability, chronic hypoxaemia, thromboembolism, parenchymal and vascular injury because of sequestration of sickle erythrocytes, chronic liver disease and asplenia. Interestingly, pulmonary hypertension is emerging as a common, and probably, invariant sequella of lifelong haemolytic anaemia in other hereditary and acquired haemolytic diseases, such as thalassaemia, stomatocytosis and spherocytosis. There are currently limited specific data on the effects of any treatment modality for pulmonary hypertension in patients with SCD. It is likely that maximization of SCD therapy, in all patients, and treatment with selective pulmonary vasodilators and antiproliferative agents, in patients with severe disease, would be beneficial. A large trial evaluating the effects of therapy for pulmonary hypertension in the SCD population is clearly indicated.     

Pulmonary hypertension in patients with sickle cell disease: a longitudinal study

Although pulmonary hypertension (PHT) is a common complication in patients with sickle cell disease (SCD), the rate of development of PHT and the factors that affect disease progression are unknown. We observed 93 patients over a median follow-up period of 2.6 years (range 0.2-5.1 years). Data were censored at the time of death or loss to follow-up. Pulmonary hypertension was associated with an increased risk of death (relative risk, 9.24; 95% confidence interval: 1.2-73.3; P = 0.01). There was no difference in the risk of death when patients with different degrees of PHT were compared. Lactate dehydrogenase and blood urea nitrogen were significantly associated with PHT in a logistic regression model. Higher levels of fetal haemoglobin and treatment with hydroxycarbamide were observed more frequently in patients without PHT. Thirteen per cent of patients with no previous evidence of PHT developed PHT following 3 years of observation. In conclusion: (1) PHT, regardless of severity, is associated with an increased risk of death in SCD patients; (2) haemolysis is strongly associated with PHT in SCD; (3) high levels of fetal haemoglobin and hydroxycarbamide therapy may decrease the occurrence of PHT; (4) screening for PHT is indicated for SCD patients in their non-crisis, steady states.