Pulmonary pharmacology & therapeutics
-
Pulm Pharmacol Ther · Jun 2010
Somatic DNA alterations in lung epithelial barrier cells in COPD patients.
Instability of the Microsatellite DNA Instability (MSI) and Loss of Heterozygosity (LOH) have been previously detected in sputum cells of COPD patients. However, the particular cell subpopulation exhibiting genetic instability in COPD was uncertain. The aim of this study was to determine which cell type expresses Microsatellite DNA Instability in sputum and BALF samples from COPD patients. ⋯ Our results support the hypothesis that chronic inflammation and oxidative burden in COPD can lead to DNA damage of the lung epithelial barrier cells, detected at the Microsatellite DNA level. Further studies are required to investigate the significance of these findings in the pathogenesis of COPD.
-
Pulm Pharmacol Ther · Jun 2010
Phosphodiesterase-5 inhibition by sildenafil citrate in a rat model of bleomycin-induced lung fibrosis.
Sildenafil, a selective and potent inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase (PDE)5, has a relaxant effect on the smooth muscle cells of the arterioles supplying the human corpus cavernosum acting via nitric oxide (NO)-dependent mechanism. This study aimed to investigate the possible protective effect of sildenafil citrate on the extent of tissue integrity, oxidant-antioxidant status and neutrophil infiltration to the inflamed organ in a rat model of bleomycin-induced lung fibrosis. Lung fibrosis was induced by intratracheal administration of 0.1 ml of bleomycin hydrochloride (5 mg/kg in 0.9% NaCl) under anesthesia to Sprague-Dawley rats (200-250 g; n = 7-8 per group). ⋯ Sildenafil reversed tissue MDA levels, MPO activity and serum pro-inflammatory cytokine levels, and preserved GSH content although its effect on the extent of tissue lesion and apoptosis was not statistically significant. Treatment with l-NAME reversed the effect of sildenafil on GSH content. In conclusion, sildenafil citrate administration to rats with bleomycin-induced lung fibrosis seems to be beneficial via prevention of lipid peroxidation, cytokine production and/or release and neutrophil accumulation.
-
Pulm Pharmacol Ther · Feb 2010
ReviewPharmacological modulation of beta-adrenoceptor function in patients with coexisting chronic obstructive pulmonary disease and chronic heart failure.
Pharmacological modulation of beta-adrenoceptor function is one of the critical issues in the treatment of patients with concurrent chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF). A volume of published evidence sustains the role of long-acting beta(2)-agonists in the treatment of stable COPD, but beta-agonists seem to be detrimental when used for long term in CHF. beta(2)-agonists may exacerbate heart failure and, in any case, they induce adverse cardiac effects in COPD patients with pre-existing cardiovascular disease. ⋯ Although the literature is reassuring, there are currently no prospective long-term studies on the safety of beta-blockers in COPD. Therefore, although beta-blockers can be introduced in any medical setting for treating patients with concurrent COPD and CHF, it still seems appropriate to only use those beta-blockers that are more selective for the beta(1)-AR but without ISA at the lowest dose and to titrate them slowly with attention to lung function and symptoms, adding an inhaled antimuscarinic agent when bronchodilation is needed.
-
Pulm Pharmacol Ther · Dec 2009
Assessment of myocardial injury in the emergency department independently predicts the short-term poor outcome in patients with severe carbon monoxide poisoning receiving mechanical ventilation and hyperbaric oxygen therapy.
Patients with severe carbon monoxide (CO) poisoning are often prone to unconsciousness and respiratory distress and as a result will receive mechanical ventilation and hyperbaric oxygen (MV-HBO) therapy. Factors associated with poor outcome at discharge are less defined in this patient population. This study was conducted to identify the prognostic predictors of short-term poor outcome in severely CO-poisoned patients receiving MV-HBO therapy. ⋯ The results of this study indicate that myocardial injury assessed at ED arrival independently predicts the short-term poor outcome in severely CO-poisoned patients who receive MV-HBO therapy. Emergency physicians could use this objective marker to identify patients with an increased risk of poor outcome at discharge and refine the treatment protocol by shortening the time of patient transport and administering HBO therapy as soon as possible.
-
Pulm Pharmacol Ther · Aug 2009
Randomized Controlled TrialEffect of inhaled corticosteroids on small airways in asthma: investigation using impulse oscillometry.
Small airways appear to have an important role in asthma. Hydrofluoroalkane-134a beclomethasone dipropionate (HFA-BDP) has ultrafine particles and accordingly greater deposition in the small airways than chlorofluorocarbon (CFC)-BDP. Impulse oscillometry systems (IOS), a new and non-invasive measure of pulmonary function, can examine the resistance of total (R5), large (R20), and small airways (R5-R20) separately, and low-frequency reactance area (AX), also considered a measure of small airways dysfunction. ⋯ HFA-BDP is an effective treatment of small airways in asthma. Prolonged treatment provides a progressive effect over time, which is associated with an attenuation of airway responsiveness.