Novel Anti-Inflammatory Agents in COPD: Targeting Lung and Systemic Inflammation.

Curr Drug Targets. 2012 Dec 17;

Authors: Loukides S, Bartziokas K, Vestbo J, Singh D

Abstract
Inflammation plays a central role in chronic obstructive pulmonary disease (COPD). COPD related inflammation is less responsive to inhaled steroids compared to asthma. There are three major novel anti-inflammatory approaches to the management of COPD. The first approach is phosphodiesterase inhibitors, such as roflumilast which provides additional clinical benefit either as a single agent or as an additive treatment to long-acting bronchodilators. The second approach involves novel strategies using drugs licensed for other indications, such as statins and macrolides; limited prospective studies on these strategies exist at the moment. A third potential approach involves novel agents whose mechanism of action is closely related to COPD mechanisms and pathophysiology. Such novel treatments are of great interest since they may treat both COPD and co-morbidities. Several novel agents are currently under development and may be of importance in the future.

PMID: 23256720 [PubMed - as supplied by publisher]

Stem Cell Therapy in Chronic Obstructive Pulmonary Disease. Seeking the Prometheus Effect.

Curr Drug Targets. 2012 Dec 17;

Authors: Tzouvelekis A, Laurent G, Bouros D

Abstract
Chronic obstructive pulmonary diseaseis characterized by dramatic alterations in lung architecture associated to an exaggerated inflammatory process, alveolar epithelial cell apoptosis, endothelial dysfunction and extracellular matrix destruction due to a protease and anti-protease imbalance. In addition a significant inflammatory spillover into systemic circulation has been suggested to be responsible for a wide range of fatal comorbidities. In view of the current disappointing status of available pharmaceutical agents, there is an urgent need for alternative more effective therapeutic approaches that will fulfill the unmet need of modulating both local and systemic inflammation and at the same time accelerate alveolar epithelial and endothelial turnover intervening into disease natural course and not only relieving patient's symptoms. Regenerative medicine based on stem cells properties represents one promising option with several fruitful therapeutic applications in patients with COPD. Nevertheless, despite relative enthusiasm arising from experimental data, application of stem cell therapy in the clinical setting has been severely hampered by several safety concerns arising from the major lack of knowledge on the fate of exogenously administrated stem cells within the COPD lung as well as the mechanisms regulating activation of resident progenitor cells. The above evidence coupled with the rather disappointing results emerging from the first stem cell clinical trials in COPD patients underline the need for careful study design by setting realistic goals to assess efficacy such as biomarkers that reflect clinically inconspicuous alterations of the disease molecular phenotype before rigid conclusions can be safely drawn. 

PMID: 23256721 [PubMed - as supplied by publisher]

Pathologically Confirmed, Early-onset, Severe Chronic Obstructive Pulmonary Disease.

Intern Med. 2012;51(24):3411-4

Authors: Tsuchida T, Matsuse H, Nishino T, Kawano T, Fukushima C, Hayashi T, Kohno S

Abstract
A 27-year-old man who had been a smoker since 14 years of age presented with exertional dyspnea. Approximately three years earlier, he had been occupationally been exposed to an organic solvent and felt dyspnea during its use. He later developed severe dyspnea and received treatment for asthma. He had no relevant family history. Chest auscultation revealed decreased breath sounds without rales. Spirometry and high-resolution computed tomography scans suggested a diagnosis of chronic obstructive pulmonary disease (COPD). Video-assisted thoracoscopic surgery performed to obtain a pathological diagnosis confirmed the presence of centrilobular emphysema. High susceptibility, smoking from an early age and organic solvent exposure may have caused early-onset COPD in this case.

PMID: 23257530 [PubMed - in process]

Pulmonary Hypertension in COPD.

Respir Care. 2012 Dec 18;

Authors: Held M, Jany B

Abstract
Pulmonary hypertension (PH) is a common consequence of chronic obstructive pulmonary disease (COPD). It has been speculated that patients showing serious PH and vascular remodelling without severe airway obstruction might benefit from vasoactive treatment. There is no approved drug available for COPD-induced PH. Most trials assessing the efficacy of vasoactive drugs in PH have a follow-up of 12-16 weeks. We report on four patients with COPD and PH. Pulmonary arterial hypertension (PAH) associated diseases and pulmonary embolism were ruled out. PH persisted despite optimized treatment of underlying COPD and comorbidities. Therefore, Bosentan treatment was started in all the 4 patients. With Bosentan treatment, the mean pulmonary artery pressure (PAP) was found to improve. The average gain in six-minute walking distance (6MWD) at 2-3 months and 8-9 months was 36 m and 145 m, respectively. The maximum gain in 6MWD of the individual patients was noticed after the 9(th), 13(th), and 18(th) month. Oxygenation was found to be stable, and no side effects were observed. We suggest from this experience that in clinical trials of PH in COPD, a follow-up of 16 weeks might lead to an underestimation of the treatment effects.

PMID: 23258580 [PubMed - as supplied by publisher]