Therapeutic Strategies in Pulmonary Hypertension

Pulmonary hypertension (PH) is a life-threatening condition characterized by elevated pulmonary arterial pressure. It is clinically classified into five groups: patients in the first group are considered to have pulmonary arterial hypertension (PAH) whereas patients of the other groups have PH that is due to cardiopulmonary or other systemic diseases. The management of patients with PH has advanced rapidly over the last decade and the introduction of specific treatments especially for PAH has lead to an improved outcome. However, despite the progress in the treatment, the functional limitation and the survival of these patients remain unsatisfactory and there is no cure for PAH. Therefore the search for an “ideal” therapy still goes on. At present, two levels of treatment can be identified: primary and specific therapy. Primary therapy is directed at the underlying cause of the PH. It also includes a supportive therapy consisting in oxygen supplementation, diuretics, and anticoagulation which should be considered in all patients with PH. Specific therapy is directed at the PH itself and includes treatment with vasodilatators such as calcium channel blockers and with vasodilatator and pathogenetic drugs such as prostanoids, endothelin receptor antagonists and phosphodiesterase type-5 inhibitors. These drugs act in several pathogenetic mechanisms of the PH and are specific for PAH although they might be used also in the other groups of PH. Finally, atrial septostomy and lung transplantation are reserved for patients refractory to medical therapy. Different therapeutic approaches can be considered in the management of patients with PH. Therapy can be established on the basis of both the clinical classification and the functional class. It is also possible to adopt a goal-oriented therapy in which the timing of treatment escalation is determined by inadequate response to known prognostic indicators

Polymorphism of Beta2-Adrenoceptor and Regular Use of Formoterol in Asthma: Preliminary Results

Polymorphism at codon 16 of the beta2-adrenoceptor (beta2-AR) affects the responsiveness to salmeterol in asthmatics. Data concerning formoterol are more controversial in the literature. The aim of this study was to verify whether homozygous for arginine-16 (ArgArg16) and homozygous for glycine-16 (GlyGly16) genotypes differently influence the long-term responsiveness to formoterol. Twenty-nine patients with mild-to-moderate asthma, in stable clinical conditions, underwent genotyping at codon 16 of the beta2-AR by RFLP-PCR assay. The effects of a 4-week monotherapy with formoterol (12 μg BID) were tested on the peak expiratory flow (PEF) variability and the forced expiratory volume in 1 sec (FEV1) slope of the dose-response curve to salbutamol. Variability in PEF significantly increased during the 4-week treatment period in 14 patients with GlyGly16, but not in 15 patients with ArgArg16 and ArgGly16 (P=0.032). The FEV1 slope of the dose-response curve to salbutamol decreased after the 4-week treatment period in GlyGly16, but not in pooled ArgArg16 and ArgGly16 patients. This study provides preliminary evidence that tolerance to formoterol develops more frequently in asthmatics with GlyGly16 genotype. If confirmed in a larger population, this finding might be useful in choosing the bronchodilator therapy on the basis of genetic polymorphism of the beta2-AR

Pneumopatie da agenti ambientali (professionali ed immunomediate)

Pneumopatie da agenti ambientali professionali ed immunomediate

Nonrespiratory determinants of respiratory impairment in elderly patients: heart failure and diabetes.

Heart failure (HF) and diabetes mellitus (DM) promote a plethora of abnormalities in lung function and, in both conditions, the lung is considered the ‘‘target organ’’ for therapeutic interventions. HF is associated with changes in lung mechanics and gas diffusion, which are the direct consequence of haemodynamic perturbations and congestion. Changes in lung mechanics may vary according to the acute or chronic manifestations of HF, with a predominant obstructive lung pattern in acute HF and a restrictive one in chronic conditions. Specific relevance has recently been given to the anatomical and functional consequence of a pressure and/or a volume overload on the lung microcirculation of HF patients. This challenges the alveolar–capillary integrity, causes an increase in capillary permeability to water and ions, and impairs local mechanisms for gas diffusion. Remarkably, an impairment in alveolar gas conductance properties reflects underlying lung tissue damage, is involved in the pathogenesis of exercise limitation and is an independent prognostic marker. Diabetes mellitus elicits an angiopathy process of the lung microvessels that leads to the development of pulmonary dysfunction and to an accelerated organ ageing process. An increasing prevalence of type 2 diabetes mellitus with age indicates that elderly subjects are more exposed to the pulmonary complications of the disease. Diabetes mellitus could also contribute to an increase in the incidence of respiratory infections both by itself and by worsening the age-related abnormalities of the respiratory system. Epidemiological and clinical studies show that diabetes mellitusrelated pulmonary involvement has important clinical and prognostic implications contributing to increased morbidity and mortality of older subjects