Brain natriuretic peptide in pulmonary arterial hypertension: biomarker and potential therapeutic agent

B-type natriuretic peptide (BNP) is a member of the natriuretic peptide family, a group of widely distributed, but evolutionarily conserved, polypeptide mediators that exert myriad cardiovascular effects. BNP is a potent vasodilator with mitogenic, hypertrophic and pro-inflammatory properties that is upregulated in pulmonary hypertensive diseases. Circulating levels of BNP correlate with mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR) in patients with pulmonary arterial hypertension (PAH). Elevated plasma BNP levels are associated with increased mortality in patients with PAH and a fall in BNP levels after therapy is associated with improved survival. These findings have important clinical implications in that a noninvasive blood test may be used to identify PAH patients at high-risk of decompensation and to guide pulmonary vasodilator therapy. BNP also has several biologic effects that could be beneficial to patients with PAH. However, lack of a convenient method for achieving sustained increases in circulating BNP levels has impeded the development of BNP as a therapy for treating pulmonary hypertension. New technologies that allow transdermal or oral administration of the natriuretic peptides have the potential to greatly accelerate research into therapeutic use of BNP for cor pulmonale and pulmonary vascular diseases. This review will examine the basic science and clinical research that has led to our understanding of the role of BNP in cardiovascular physiology, its use as a biomarker of right ventricular function and its therapeutic potential for managing patients with pulmonary vascular disease

Ambrisentan for the treatment of pulmonary arterial hypertension

Ambrisentan is an endothelin receptor antagonist (ERA) that was recently approved for treatment of pulmonary arterial hypertension (PAH). Endothelin (ET) is a potent vasoconstrictor with mitogenic, hypertrophic and pro-inflammatory properties that is upregulated in pulmonary hypertensive diseases. The biologic effects of ET are mediated by 2 cell surface receptors termed ETA and ETB. ETA mediates the vasoconstrictor effect of ET on vascular smooth muscle, whereas ETB is expressed primarily on vascular endothelial cells where it induces nitric oxide synthesis and acts to clear ET from the circulation. Ambrisentan is the first ETA selective ERA approved for use in the US. Recently published clinical trials in patients with PAH demonstrate improvement in functional capacity and pulmonary hemodynamics similar to other ETA selective and non-selective ERAs. Its once daily dosing and lower incidence of serum aminotransferase elevation offer potential advantages over other ERAs, but further experience with this agent is needed to fully understand its long-term efficacy and safety. This review discusses the endothelin family of proteins and receptors and their role in the pathophysiology of pulmonary hypertensive diseases. It also examines the development process, safety profile and clinical trials that have resulted in ambrisentan being approved for treatment of PAH

Hamman-Rich syndrome: a forgotten entity

The following report outlines the case of a 76-year-old gentleman who presented to the hospital with acute interstitial pneumonitis, a rare and rapidly progressive type of idiopathic interstitial pneumonia. The patient initially presented with a three-week history of progressive shortness of breath and cough which was diagnosed as community acquired pneumonia. Treatment with oral antibiotics was unsuccessful resulting in re-presentation the following week with type one respiratory failure. Investigations revealed widespread inflammatory changes consistent with an acute inflammatory process. Intravenous steroids, antibiotics and antiviral medications were initiated before an urgent transfer to the intensive care unit was required for intubation. An open lung biopsy, in conjunction with the clinical picture, confirmed the diagnosis of acute interstitial pneumonitis. The significance of this report is to highlight the rapid and destructive clinical course of a rare type of pneumonitis, which initially presented as a routine and innocuous diagnosis in our patient

Air embolism following bronchoscopy with fine needle aspiration: an unexpected complication

Flexible fibreoptic bronchoscopy with fine needle aspiration is a common procedure, useful in the diagnosis and assessment of lung disease. There are known complications associated with such a procedure that are well documented in the literature. However, there are only four cases of air embolus following fine needle aspiration during bronchoscopy described in the literature. Due to the varying clinical manifestations of the complication, it remains underrecognized by the clinical community and was not described at all by the most recent British Thoracic society 2013 statement on bronchoscopy. The following two case reports describe incidences where air emboli ensued following bronchoscopy with fine needle aspiration. They examine four notable, and arguably avoidable, risk factors that can exacerbate an air embolus and offer guidance on both imaging and treatment for any physician faced with a corresponding clinical pictur

Into the Wild(ish)

The author describes his trip down the Allagash, the river\u27s history, and how part of it came to be the Allagash Wilderness Waterway in 1966. [images

A pyo-hydropneumothorax with sepsis, secondary to Gardnerella vaginalis infection in a post-partum female

A 20 year old female, 14 days post partum, presented to the Emergency Department in severe respiratory distress. Imaging of her chest revealed a left tension hydropneumothorax with significant mediastinal displacement. A chest drain was inserted and over 4L of cloudy-brown malodourous fluid was drained. Gardnerella Vaginalis was isolated on culture of the fluid. The pyohydropneumothorax and associated sepsis, was refractory to management with a chest drain and antimicrobial therapy. She required a video-assisted thoracoscopic surgery and decortication of her unexpanded lung. She ultimately made a full recovery. Gardnerella vaginalis is considered a dysbiosis of the genitourinary tract, rather than an overtly virulent pathogen. Although extremely rare, there are occasional reports of Gardnerella vaginalis causing infection, even at sites distant from the genitourinary tract. To our knowledge, this is the first documented case of Gardnerella vaginalis causing respiratory sepsis and a pyohydropneumothorax in a healthy, immunocompetent female during the post-partum period. Although it is a unique case, nevertheless, it highlights the need for physicians to be congnisant of G. vaginalis as a potential pathogen when treating post-partum sepsis and indeed, even as a potential pathogen when treating pulmonary infections in obstetric patients. This will lend to prompt initiation of appropriate antimicrobial treatment. Keywords: Pneumothorax, Post-partum, Sepsis, Gardnerella vaginali