Pulmonary pharmacology & therapeutics
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Pulm Pharmacol Ther · Jun 2013
Efficacy and safety of indacaterol and tiotropium in COPD patients according to dyspnoea severity.
Guidelines for chronic obstructive pulmonary disease (COPD) recommend that treatment choices be based partly on symptoms. ⋯ In patients with less dyspnoea, all treatments had similar effects. Indacaterol 300 μg may be a useful treatment option for patients with COPD who experience more severe breathlessness.
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Pulm Pharmacol Ther · Jun 2013
Methacholine PC20 in African Americans and whites with asthma with homozygous genotypes at ADRB2 codon 16.
African Americans have worse asthma outcomes compared to whites. Adrenoceptor beta 2, surface gene (ADRB2) Gly16Arg genotypes have been associated with β2-agonist bronchodilator response, asthma exacerbation rate, response to methacholine, and lung function decline but not specifically in African Americans. ⋯ Airway hyperresponsiveness is influenced by race and the ADRB2 codon 16 polymorphism. African Americans with the Arg16Arg genotype have increased airway reactivity and may be at risk for worse asthma outcomes. Inclusion of genetic information as an additional clinical tool may aid in the personalization of asthma management decisions. [ClinicalTrials.gov Identifier: NCT00708227].
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Pulm Pharmacol Ther · Jun 2013
Multidetector-row computed tomography assessment of adding budesonide/formoterol to tiotropium in patients with chronic obstructive pulmonary disease.
In patients with chronic obstructive pulmonary disease (COPD), multidetector-row computed tomography (MDCT) showed that tiotropium dilated the inner diameters in airways from the third to the sixth generation of the bronchi. Here we aimed to evaluate the morphological effect by adding a budesonide/formoterol combination to tiotropium in COPD patients using three-dimensional MDCT. ⋯ MDCT demonstrated budesonide/formoterol induced bronchodilation in the non-small airway. CT imaging can evaluate drug therapeutic effect and may provide additional insights into pharmacotherapy for COPD.
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Pulm Pharmacol Ther · Jun 2013
Knockdown of myeloid differentiation protein-2 reduces acute lung injury following orthotopic autologous liver transplantation in a rat model.
Acute lung injury (ALI) is a serious complication that commonly occurs during orthotopic liver transplantation (OLT). Toll-like receptor 2/4 (TLR2/4) are the main membrane receptors that respond to inflammatory stimuli and mediate NF-kappa B (NF-κB) signal pathway. We previously showed that TLR2/4 expression on monocytes and serum cytokine levels were increased in patients with ALI induced by OLT. Myeloid differentiation protein-2 (MD-2) expresses the functional domains that combines TLRs and play a key regulatory role in TLRs activation. Therefore, we hypothesized that blocking MD-2 would inhibit the TLR2/4-mediated inflammatory response and lessen ALI induced by liver transplantation. ⋯ MD-2 gene knock-down attenuated the increase in TLR2/4 activation and reduced ALI after OALT.
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Pulm Pharmacol Ther · Jun 2013
AP301, a synthetic peptide mimicking the lectin-like domain of TNF, enhances amiloride-sensitive Na(+) current in primary dog, pig and rat alveolar type II cells.
Pulmonary permeability oedema is a frequent complication in a number of life-threatening lung conditions, such as ALI and ARDS. Apart from ventilation strategies, no specific therapy yet exists for treatment of these potentially fatal illnesses. The oedema-reducing capacity of the lectin-like domain of TNF (TIP) and of synthetic peptides, mTIP and hTIP, which mimic the TIP domain of mouse and human TNF, have been demonstrated in various studies in rodents. ⋯ These results provide strong evidence that AP301 activates the amiloride-sensitive Na(+) current through ENaC in type II AEC from dog, pig and rat. To our knowledge, this is the first cell-based analysis of the oedema-clearing effect of AP301 observed in the porcine model of pulmonary oedema. Furthermore, the results validate the dog and pig models in non-clinical assessment of AP301.