Background: Diagnostic criteria for mast cell (MC) activation syndrome have been recently proposed, but clinical studies to validate these criteria are lacking.Objective: We sought to determine the clinical manifestations of this newly recognized syndrome in a cohort of patients.Methods: We prospectively evaluated 18 patients seen at our institution with MC activation syndrome from 2006 to 2009. Patients enrolled had at least 4 of the signs and symptoms of abdominal pain, diarrhea, flushing, dermatographism, memory and concentration difficulties, or headache. Response to treatment with anti-MC mediator medications was assessed based on established criteria. Laboratory tests indicating MC mediator release and histopathology and immunohistochemical studies on gastrointestinal biopsy samples were performed.Results: Ninety-four percent of the patients had abdominal pain, 89% had dermatographism, 89% had flushing, and 72% had the constellation of all 3 symptoms. Patients additionally had headache, diarrhea, and memory and concentration difficulties. All patients had at least 1 positive laboratory test result for an increased MC mediator level. On the basis of the response to treatment criteria, 67% of the patients in the cohort had either a complete or major regression in symptoms while taking medications targeting MC mediators. There was no significant difference in the numbers of intestinal mucosal MCs between our patients and healthy control subjects.Conclusion: MC activation syndrome might be the underlying cause of unexplained symptoms when several organ systems are involved, such as the gastrointestinal tract and the skin. It is especially important to be able to recognize the constellation of clinical features because response to anti-MC mediator medications is often excellent.

Pulmonary arterial hypertension (PAH) is a clinical condition characterised by the presence of precapillary pulmonary hypertension (PH). Included within the subcategorisation of PAH are heritable (HPAH) and PAH associated various conditions (APAH) including systemic sclerosis (SSc). The pathogenesis of HPAH and SSc has been linked to both a genetic predisposition and epigenetic factors. TGF-β superfamily signalling has also been implicated in the development of these conditions. In this review, we discuss the role of genetic predisposition, epigenetic factors along with dysregulation in TGF-β superfamily signalling in the pathogenesis of PAH and SSc.

The WHO classification of pulmonary hypertension (PH) recognises five distinct groups, all sharing a mean, resting, pulmonary artery pressure (PAP) > 25 mmHg. The aetiology of PH varies by group (1-pulmonary vascular disease, 2-high left heart filling pressures, 3-hypoxia, 4-unresolved pulmonary embolism and 5-miscellaneous). Inclusion in a group reflects shared histological, haemodynamic and pathophysiological features and has therapeutic implications. Advantages of using rodent models to understand the pathophysiology of human PH and to test experimental therapies include the economy, safety and mechanistic certainty they provide. As rodent models are meant to reflect human PH, they should be categorised by a parallel PH classification and limitations in achieving this ideal recognised. Challenges with rodent models include: accurate phenotypic characterisation (haemodynamics, histology and imaging), species and strain variations in the natural history of PH, and poor fidelity to the relevant human PH group. Rat models of group 1 PH include: monocrotaline (± pneumonectomy), chronic hypoxia + SU-5416 (a VEGF receptor inhibitor) and the fawn-hooded rat (FHR). Mouse models of group 1 PH include: transgenic mice overexpressing the serotonin transporter or dominant-negative mutants of bone morphogenetic protein receptor-2. Group 1 PH is also created by infecting S100A4/Mts1 mice with γ-herpesvirus. The histological features of group 1 PH, but not PH itself, are induced by exposure to Schistosoma mansoni or Stachybotrys chartarum. Group 3 PH is modelled by exposure of rats or mice to chronic hypoxia. Rodent models of groups 2, 4 and 5 PH are needed. Comprehensive haemodynamic, histological and molecular phenotyping, coupled with categorisation into WHO PH groups, enhances the utility of rodent models.

Conclusions:  Esomeprazole did not have a clinically important effect greater than placebo in patients with cough. It suggests a marked placebo effect in the treatment of cough. (Source: Respirology)