Angiogenesis in pulmonary fibrosis: too much or not enough?

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and usually fatal disease, based on a multifaceted and incompletely understood pathogenesis. Some of the cellular and molecular mechanisms of vascular remodeling have been experimentally explored, and it is obvious that alterations of microvessels are involved in IPF. These can, among others, lead to the development of pulmonary hypertension. In order to understand the process of vascular integrity and repair, it is necessary to identify the factors associated with angiogenesis in IPF. A delicate balance of angiogenic and angiostatic factors regulates vessel homeostasis in normal physiologic conditions in the lungs. Although earlier studies have proposed that IPF is associated with an increase of angiogenesis, there is some more recent evidence that angiogenesis in fibrotic lungs may actually be decreased, causing some controversy in the literature in this area. This review, therefore, discusses the concept of angiogenesis in pulmonary fibrosis and speculates on how the spatial and temporal heterogeneity of IPF might explain the controversial findings about vessel density in fibrotic lungs.     

Iron: how much is too much?

Gross iron overload has long been known to result in diabetes mellitus. However, it is now thought that milder levels of iron overload, possibly within the normal range, also increase the risk of diabetes mellitus. The article by Rawal et al in this issue (Diabetologia doi:  10.1007/s00125-016-4149-3) provides further support for the relationship between mild degrees of iron overload and the risk of gestational diabetes. The purpose of this commentary is to briefly discuss the background of this relationship and the implications it may have for routine pregnancy care.     

Are we giving too much iron? Low-dose iron therapy is effective in octogenarians

PURPOSE: Elderly patients are vulnerable to the dose-dependent adverse effects of iron replacement therapy. Our study examines whether low-dose iron therapy can efficiently resolve iron-deficiency anemia in patients over the age of 80 years and reduce adverse effects. SUBJECTS AND METHODS: Ninety hospitalized patients with iron-deficiency anemia were randomized to receive elemental iron in daily doses of 15 mg or 50 mg as liquid ferrous gluconate or 150 mg of ferrous calcium citrate tablets for 60 days. Thirty control patients without anemia were given 15 mg of iron for 60 days. A 2-hour iron absorption test was performed after the initial dose. Hemoglobin and ferritin levels were measured on day 1, 30, and 60 after initiating therapy. Each patient completed a weekly questionnaire regarding drug-induced adverse effects. RESULTS: Serum iron rose significantly in the anemic patients beginning 15 minutes after the first dose but not in nonanemic patients. Two months of iron treatment significantly increased hemoglobin and ferritin concentrations similarly in all 3 groups of iron-deficiency anemia patients (for example, hemoglobin levels rose from 10.0 g/dL to 11.3 g/dL with 15 mg/d of iron therapy and from 10.2 g/dL to 11.6 g/dL with 150 mg/d). Abdominal discomfort, nausea, vomiting, changes in bowel movements, and black stools were significantly more common at higher iron doses. CONCLUSIONS: Low-dose iron treatment is effective in elderly patients with iron-deficiency anemia. It can replace the commonly used higher doses and can significantly reduce adverse effects.     

Supplementation with oral vs. intravenous iron for anemia with IBD or gastrointestinal bleeding: is oral iron getting a bad rap?

Although iron supplementation is commonly prescribed, the amount of elemental iron needed to achieve clinical efficacy, and the optimal method of supplementation, are under debate. Use of intravenous (IV) iron replacement is increasingly being advocated. We explore the physiology of iron supplementation, review clinical data suggesting that the typical oral dosing of iron may be excessive, and compare IV and oral methods of iron supplementation with a focus on inflammatory bowel disease (IBD). Both IV and oral iron can effectively raise hemoglobin levels in iron-deficiency anemia. There is no evidence that IV iron can raise hemoglobin at a faster pace. Side effects of oral iron are probably related to the relatively high doses of elemental iron that are typically prescribed. Emerging data suggest that low-dose iron has comparable efficacy, with fewer side effects. In IBD, both oral and IV iron are effective, and there is no convincing evidence that oral iron activates or exacerbates clinical symptoms. The use of a low starting dose of oral iron, such as one ferrous sulfate tablet per day, for treatment of iron deficiency is worth considering.     

Iron therapy for the treatment of iron deficiency in chronic heart failure: intravenous or oral?

This article considers the use and modality of iron therapy to treat iron deficiency in patients with heart failure, an aspect of care which has received relatively little attention compared with the wider topic of anaemia management. Iron deficiency affects up to 50% of heart failure patients, and is associated with poor quality of life, impaired exercise tolerance, and mortality independent of haematopoietic effects in this patient population. The European Society of Cardiology Guidelines for heart failure 2012 recommend a diagnostic work‐up for iron deficiency in patients with suspected heart failure. Iron absorption from oral iron preparations is generally poor, with slow and often inefficient iron repletion; moreover, up to 60% of patients experience gastrointestinal side effects. These problems may be exacerbated in heart failure due to decreased gastrointestinal absorption and poor compliance due to pill burden. Evidence for clinical benefits using oral iron is lacking. I.v. iron sucrose has consistently been shown to improve exercise capacity, cardiac function, symptom severity, and quality of life. Similar findings were observed recently for i.v. ferric carboxymaltose in patients with systolic heart failure and impaired LVEF in the double‐blind, placebo‐controlled FAIR‐HF and CONFIRM‐HF trials. I.v. iron therapy may be better tolerated than oral iron, although confirmation in longer clinical trials is awaited. Routine diagnosis and management of iron deficiency in patients with symptomatic heart failure regardless of anaemia status is advisable, and, based on current evidence, prompt intervention using i.v. iron therapy should now be considered.     

Device therapy in patients with heart failure and advanced age: too much too late?

Expanding indications for implantable cardiac rhythm devices coupled with the aging of the population have led to a progressive rise in the number of elderly patients referred for device implantation. However, the value of implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy (CRT) in elderly patients remains unproven, in part because few patients over 75 years of age were enrolled in the major device trials. In this article, we summarize the current evidence base regarding the use of device therapy in elderly heart failure patients. We review the efficacy, complications, indications, cost, and current controversies surrounding the use of ICDs and CRT in the geriatric age group. We conclude that reduced benefit coupled with higher complication rates and associated higher costs make it unlikely that the net clinical benefit of an ICD is favorable in most patients over 75 to 80 years of age. Conversely, preliminary data indicate that elderly patients undergoing CRT experience improved quality of life at acceptable cost, suggesting that CRT may be an attractive therapeutic option in appropriately selected patients of advanced age.