Related Articles

Cellular interplay in pulmonary arterial hypertension: implications for new therapies.

Biochim Biophys Acta. 2014 May;1843(5):885-93

Authors: Nogueira-Ferreira R, Ferreira R, Henriques-Coelho T

Abstract
Pulmonary arterial hypertension (PAH) is a complex and multifactorial disease characterized by vascular remodeling, vasoconstriction, inflammation and thrombosis. Although the available therapies have resulted in improvements in morbidity and survival, PAH remains a severe and devastating disease with a poor prognosis and a high mortality, justifying the need of novel therapeutic targets. An increasing number of studies have demonstrated that endothelial cells (ECs), smooth muscle cells (SMCs) and fibroblasts of the pulmonary vessel wall, as well as platelets and inflammatory cells have a role in PAH pathogenesis. This review aims to integrate the interplay among different types of cells, during PAH development and progression, and the impact of current therapies in cellular modulation. The interplay among endothelial cells, smooth muscle cells and fibroblasts present in pulmonary vessels wall, platelets and inflammatory cells is regulated by several mediators produced by these cells, contributing to the pathophysiologic features of PAH. Current therapies are mainly focused in the pulmonary vascular tone and in the endothelial dysfunction. However, once they have not been effective, novel therapies targeting other PAH features, such as inflammation and platelet dysfunction are emerging. Further understanding of the interplay among different vascular cell types involved in PAH development and progression can contribute to find novel therapeutic targets, decreasing PAH mortality and morbidity in the future.

PMID: 24491811 [PubMed - indexed for MEDLINE]

Related Articles

Impact of pulmonary hypertension on exercise performance in patients with interstitial lung disease undergoing evaluation for lung transplantation.

Respirology. 2014 May 6;

Authors: Armstrong HF, Schulze PC, Bacchetta M, Thirapatarapong W, Bartels MN

Abstract
BACKGROUND AND OBJECTIVE: Pulmonary hypertension (PH) is a known complication in patients with interstitial lung disease (ILD). Cardiopulmonary exercise testing (CPET) is an essential tool for the assessment of patients with cardiac and pulmonary diseases due to its prognostic and therapeutic implications. Few studies have evaluated the relationship between CPET response and mean pulmonary artery pressures (mPAP) in ILD. The purpose of the present study was to determine and compare the potential correlations between CPET, 6-min walk test (6MWT), pulmonary function testing (PFT) and PH in patients with ILD being evaluated for lung transplantation.
METHODS: The present study reviewed patients with ILD who received lung transplantations and had CPETs within 2 years before transplantation, right heart catheterizations, PFTs and 6MWTs within 4 months of CPET.
RESULTS: A total of 72 patients with ILD were analysed; 36% had PH. There were significant correlations between mPAP and CPET parameters in patients with PH; but mPAP had no impact on percent of predicted diffusion capacity of the lung for carbon monoxide or 6-min walk distance (6MWD). CPET parameters were able to detect differences between levels of severity of PH through the use of the ratio of minute ventilation to rate of carbon dioxide production ( V ˙ E / V ˙ C O 2 ) and the partial pressure of end-tidal carbon dioxide.
CONCLUSIONS: This is the first study that analyses 6MWD, PFT and CPET in patients with ILD awaiting lung transplantation with and without PH. The present study demonstrates the significant impact of PH on exercise capacity and performance in patients with ILD awaiting lung transplantation.

PMID: 24797365 [PubMed - as supplied by publisher]

Use of pressurized metered dose inhalers in patients with chronic obstructive pulmonary disease: review of evidence.

Expert Rev Respir Med. 2014 May 7;

Authors: Aggarwal B, Gogtay J

Abstract
The inhaled route is considered to be the best route to administer drugs for treating respiratory diseases like asthma and chronic obstructive pulmonary disease (COPD), for both safety and efficacy. Inhalation devices are classified into four types - pressuriszed metered dose inhalers (pMDIs), dry powder inhalers, breath actuated inhalers and nebulizers. pMDIs are portable, convenient, multi-dose devices and these advantages have made them very popular with patients. They were introduced in the 1950s as the first portable, multi-dose delivery system for bronchodilators. Even though pMDIs are the most widely used devices for inhalation therapy in asthma and COPD, studies establishing their use and providing clinical data with bronchodilators and combination therapies in patients with COPD are limited. A summary of the use of pMDI with spacers in patients with COPD in terms of lung deposition and impact on lung function are presented in this review article. A review of use of the pMDI device in patients with COPD with different available and prescribed medications (bronchodilators-β2-agonists and anticholinergics, and their combination with inhaled corticosteroids) is discussed.

PMID: 24802511 [PubMed - as supplied by publisher]

Related Articles

Novel Simvastatin Inhalation Formulation and Characterisation.

AAPS PharmSciTech. 2014 May 8;

Authors: Tulbah AS, Ong HX, Colombo P, Young PM, Traini D

Abstract
Simvastatin (SV), a drug of the statin class currently used orally as an anti-cholesterolemic via the inhibition of the 3-hydroxy-3-methyl-glutaryl-Coenzyme A (HMG-CoA) reductase, has been found not only to reduce cholesterol but also to have several other pharmacological actions that might be beneficial in airway inflammatory diseases. Currently, there is no inhalable formulation that could deliver SV to the lungs. In this study, a pressurised metered-dose inhaler (pMDI) solution formulation of SV was manufactured, with ethanol as a co-solvent, and its aerosol performance and physico-chemical properties investigated. A pMDI solution formulation containing SV and 6% w/w ethanol was prepared. This formulation was assessed visually and quantitatively for SV solubility. Furthermore, the aerosol performance (using Andersen Cascade impactor at 28.3 L/min) and active ingredient chemical stability up to 6 months at different storage temperatures, 4 and 25°C, were also evaluated. The physico-chemical properties of the SV solution pMDI were also characterised by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and laser diffraction. The aerosol particles, determined using scanning electron microscopy (SEM), presented a smooth surface morphology and were spherical in shape. The aerosol produced had a fine particle fraction of 30.77 ± 2.44% and a particle size distribution suitable for inhalation drug delivery. Furthermore, the short-term chemical stability showed the formulation to be stable at 4°C for up to 6 months, whilst at 25°C, the formulation was stable up to 3 months. In this study, a respirable and stable SV solution pMDI formulation for inhalation has been presented that could potentially be used clinically as an anti-inflammatory therapy for the treatment of several lung diseases.

PMID: 24806822 [PubMed - as supplied by publisher]