"Management of myositis associated interstitial lung disease".

Idiopathic inflammatory myopathies (IIM) are rare disorders characterised by the presence of skeletal muscle inflammation, with interstitial lung disease (ILD) being the most frequent pulmonary manifestation. The spectrum of clinical presentations of myositis related ILD (M-ILD) encompasses a chronic process to a rapidly progressive ILD (RP-ILD); which is associated with a high mortality rate. The most effective treatments remain controversial and poses a unique challenge to both rheumatologists and respiratory physicians to manage. Given the rare heterogenous nature of M-ILD, there is a paucity of data to guide treatment. The cornerstone of existing treatments encompasses combinations of immunosuppressive therapies, as well as non-pharmacological therapies. In this review, we aim to summarize the current pharmacological therapies (including its dosing regimens and side effects profiles) and non-pharmacological therapies. Based on the existing literature to date, we propose a treatment algorithm for both chronic M-ILD and RP-ILD.

Trials and Treatments: An Update on Pharmacotherapy for Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive fibrosing interstitial lung disease that occurs predominantly in the older population. There is increasing incidence and prevalence in IPF globally. The emergence of anti-fibrotic therapies in the last decade have improved patient survival though a cure is yet to be developed. In this review article, we aim to summarize the existing and novel pharmacotherapies for the treatment of IPF (excluding treatments for acute exacerbations), focusing on the current knowledge on the pathophysiology of the disease, mechanism of action of the drugs, and clinical trials.

Lactate Alters Metabolism in Human Macrophages and Improves Their Ability to Kill Mycobacterium tuberculosis.

In order to mount an appropriate immune response to infection, the macrophage must alter its metabolism by increasing aerobic glycolysis and concomitantly decreasing oxidative phosphorylation; a process known as the Warburg effect. Consequently, lactate, the end-product of glycolysis, accumulates in the extracellular environment. The subsequent effect of lactate on surrounding macrophages is poorly understood. Mycobacterium tuberculosis (Mtb), the causative organism of Tuberculosis (TB), is phagocytosed by macrophages in the airways. Mtb infected macrophages upregulate aerobic glycolysis and effector functions to try to kill the bacteria. Our lab has previously shown that human macrophages produce lactate in response to infection with Mtb. Although lactate has largely been considered a waste product of aerobic glycolysis, we hypothesised that the presence of extracellular lactate would impact subsequent immunometabolic responses and modulate macrophage function. We demonstrate that the presence of exogenous lactate has an immediate effect on the cellular metabolism of resting human macrophages; causing a decrease in extracellular acidification rate (ECAR; analogous to the rate of glycolysis) and an increase in the oxygen consumption rate (OCR; analogous to oxidative phosphorylation). When lactate-treated macrophages were stimulated with Mtb or LPS, glycolysis proceeds to increase immediately upon stimulation but oxidative phosphorylation remains stable compared with untreated cells that display a decrease in OCR. This resulted in a significantly reduced ECAR/OCR ratio early in response to stimulation. Since altered metabolism is intrinsically linked to macrophage function, we examined the effect of lactate on macrophage cytokine production and ability to kill Mtb. Lactate significantly reduced the concentrations of TNF and IL-1ß produced by human macrophages in response to Mtb but did not alter IL-10 and IL-6 production. In addition, lactate significantly improved bacillary clearance in human macrophages infected with Mtb, through a mechanism that is, at least in part, mediated by promoting autophagy. These data indicate that lactate, the product of glycolysis, has a negative feedback effect on macrophages resulting in an attenuated glycolytic shift upon subsequent stimulation and reduced pro-inflammatory cytokine production. Interestingly, this pro-resolution effect of lactate is associated with increased capacity to kill Mtb.

High prevalence of risk factors for low bone mineral density and estimated fracture and fall risk among elderly medical inpatients: a missed opportunity.

AIMS: (1) To calculate the absolute fracture risk by using the fracture risk assessment (FRAX) model among elderly medical inpatients; (2) to assess the risk of falls, especially among patients with increased risk of fractures; and (3) to design and implement a bone health protocol to improve the assessment of fracture risk. METHODS: The study participants were all inpatients admitted to the medical wards at University Hospital Kerry, Ireland. All consecutive eligible patients aged ≥ 65 years were prospectively evaluated to populate clinical risk factor variables used in the FRAX model and the fall assessment was made by using Fracture Risk Questionnaire. RESULTS: Consecutive 465 medical inpatients were screened, and 200 eligible medical inpatients were evaluated. The mean age of the cohort was 73.8 ± 9 years and 56% were male. The body mass index of the cohort was 27 ± 5, and only 21% (n = 42) of patients reported having ever had a DXA scan. Previous personal history of low fragility fracture was present in 20.5% (n = 41) of the patients. The absolute 10-year risk of major osteoporotic and hip fracture was 15 ± 12 and 7.6 ± 11, respectively, and 25.5% (n = 51) and 64.5% (n = 129) respectively of the cohort had fracture risks exceeding the National Osteoporosis Federation (NOF) thresholds for treatment. High fall risk was noted in 63% of the cohort. CONCLUSIONS: A very high prevalence of fracture and fall risk was noted. A medical inpatient stay offers a window of opportunity for assessment of osteoporotic fracture risk. With these findings, a bone health protocol has been developed.

The Effects of Statin Therapy on the Human Airway.

BACKGROUND: Statins have been long known for their lipid-lowering properties however there has been recent interest in their potential to positively influence clinical outcomes in pulmonary disease processes manifesting primarily as airway disorders. OBJECTIVES: We review the potential use of statin therapy in respiratory medicine, with particular emphasis on airway disease. We also explore the possible mechanisms for the observed benefits of statins in conditions of the airway. METHOD: A literary review of published articles related to defining the potential scientific basis for touted clinical efficacy, pertinent clinical data and review articles of statin therapy in airway disease. RESULTS: There was a vast quantity of publications available pertaining to the topic of interest. CONCLUSION: Statins may have beneficial pleiotropic effects in addition to their actions as potent lipid-lowering agents particularly in patients with chronic obstructive pulmonary disease and post lung transplantation. Further human studies are required to substantiate their possible potential as many of the clinical trials performed to date have not demonstrated the translation of results of these promising scientific and observational studies into positive outcomes in well-designed, randomized, placebo-controlled human trials.

Herpetic tracheitis in association with rituximab therapy.

A 58-year old lady under active follow-up with the respiratory services at our institution for bronchiectasis secondary to hypogammaglobulinaemia presented with hoarseness and haemoptysis. She was also receiving rituximab maintenance therapy for follicular lymphoma. Bronchoscopy demonstrated vesicular lesions on her vocal cords and trachea, confirmed as herpes simplex virus (HSV) on cytological analysis of brushings. She responded well to intravenous valacyclovir. Rituximab is increasingly utilised in the treatment of haematological and auto-immune disorders. This case highlights the potential of this drug to potentiate susceptibility to infection in an already immunocompromised individual.