N Engl J Med. 2012 Jul 26;367(4):340-7
Authors: Wenzel RP, Fowler AA, Edmond MB
PMID: 22830464 [PubMed - in process]

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Background: Matrix metalloproteinase-9 (MMP-9) and its inhibitor tissue inhibitor of metalloproteinase-1 (TIMP-1) are involved in the pathogenesis of airway inflammation in patients with chronic obstructive pulmonary disease (COPD). However, no study so far has addressed their value as noninvasive biomarkers of airways inflammation.

Objective: To evaluate MMP-9 and TIMP-1 concentrations in the exhaled breath condensate (EBC) of patients with stable COPD and also during the exacerbation episode.

Methods: EBC and serum samples were collected in 17 stable-phase COPD patients who were current smokers as well as during their first exacerbation episode, and in 22 asymptomatic smokers. EBC and serum levels of MMP-9 and TIMP-1 were measured with ELISA kit.

Results: Mean EBC MMP-9 and TIMP-1 levels were higher in patients with stable COPD than in asymptomatic smokers. Exacerbation of COPD increased 2-fold the exhalation of MMP-9 (18.5 ± 10.1 ng/ml vs. 8.9 ± 6.2 ng/ml, p = 0.01) and TIMP-1 (to 41.1 ± 20.4 ng/ml vs. 16.4 ± 6.8 ng/ml, p < 0.001). Both, MMP-9 and TIMP-1 in EBC correlated negatively with FEV(1) (% predicted) at baseline (r = -0.78, p < 0.001 and r = -0.73, p < 0.001) and during the exacerbation episode (r = -0.57, p = 0.02 and r = -0.65, p = 0.005). Similar negative correlations were noted with FVC (% predicted), except for MMP-9 in EBC at exacerbation. Exhaled MMP-9 and TIMP-1 did not correlate with serum concentrations in COPD patients, either at baseline or during exacerbation.

Conclusion: Exhaled MMP-9 and TIMP-1 increased during COPD exacerbation and was negatively correlated with spirometric variables, which suggests the usefulness of their measurement in EBC for the monitoring of airways inflammation. However, to better assess their diagnostic or prognostic value larger studies are necessary.

Roflumilast is a selective phosphodiesterase 4 inhibitor which has been licensed in the European Union since 2010 and in Switzerland since November 2011 as an add-on treatment for patients with chronic obstructive pulmonary disease (COPD) in GOLD (Global Initiative for Chronic Obstructive Lung Disease) stages 3 and 4 (FEV1 <50% predicted after bronchodilatation) and frequent exacerbations despite correctly-dosed therapy with a long-acting bronchodilator.

Roflumilast is designed to target both the systemic and pulmonary inflammation associated with COPD. In this review roflumilast's chemistry, pharmacodynamics, pharmacokinetics, clinical efficacy, safety and tolerability and the current ongoing clinical trials involving roflumilast are outlined. Information has been sourced from the Swiss and US product information monographs, peer-reviewed published literature (identified from a PubMed MEDLINE search 1966 - March 2012 using the term "roflumilast"), the COPD GOLD international guidelines for the management of COPD (Revised 2011) and an independent analysis of phase 3 clinical trial data by FDA staff physicians.

Clinical efficacy in terms of a modest gain in FEV1% and a reduction in exacerbation rate has been demonstrated in phase 3 clinical trials and roflumilast has been recently incorporated into international treatment guidelines. However data examining roflumilast as add-on therapy to long-acting bronchodilators and ICS (standard therapy) is currently awaited and phase 4 post-marketing studies are required to determine the incidence and severity of adverse events and the long-term beneficial effects of roflumilast as a maintenance therapy for COPD in every-day clinical practice.

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Lung radiofrequency ablation for the treatment of unresectable recurrent non-small-cell lung cancer after surgical intervention.

Cardiovasc Intervent Radiol. 2012 Jun;35(3):563-9

Authors: Kodama H, Yamakado K, Takaki H, Kashima M, Uraki J, Nakatsuka A, Takao M, Taguchi O, Yamada T, Takeda K

Abstract
PURPOSE: A retrospective evaluation was done of clinical utility of lung radiofrequency (RF) ablation in recurrent non-small-cell lung cancer (NSCLC) after surgical intervention.
METHODS: During May 2003 to October 2010, 44 consecutive patients (26 male and 18 female) received curative lung RF ablation for 51 recurrent NSCLC (mean diameter 1.7±0.9 cm, range 0.6 to 4.0) after surgical intervention. Safety, tumor progression rate, overall survival, and recurrence-free survival were evaluated. Prognostic factors were evaluated in multivariate analysis.
RESULTS: A total of 55 lung RF sessions were performed. Pneumothorax requiring pluerosclerosis (n=2) and surgical suture (n=1) were the only grade 3 or 4 adverse events (5.5%, 3 of 55). During mean follow-up of 28.6±20.3 months (range 1 to 98), local tumor progression was found in 5 patients (11.4%, 5 of 44). The 1-, 3-, and 5-year overall survival rates were 97.7, 72.9, and 55.7%, respectively. The 1- and 3-year recurrence-free survival rates were 76.7 and 41.1%, respectively. Tumor size and sex were independent significant prognostic factors in multivariate analysis. The 5-year survival rates were 73.3% in 18 women and 60.5% in 38 patients who had small tumors measuring≤3 cm.
CONCLUSION: Our results suggest that lung RF ablation is a safe and useful therapeutic option for obtaining long-term survival in treated patients.

PMID: 21748451 [PubMed - indexed for MEDLINE]