Many lung diseases have high morbidity and mortality rates and there are no cures or treatments apart from mechanical ventilation or transplantation. Cell-based therapies are currently an area of intense research, and many groups are working to translate successful in vitro results into treatments that are safe for patients.

This review discusses several types of stem and progenitor cells that have been proven likely candidates for cell therapies, as well as their applications so far in specific acute and chronic lung diseases, focusing on their mechanisms of action and how best they can be directed toward clinical aims.

Expert opinion: The research on cell therapies for the lung, particularly regarding mesenchymal stem cells (MSCs), is promising, but there is still much uncertainty surrounding the mechanisms of MSC action and the factors relevant to clinical applications such as the optimal timing of dosage. Future studies will focus on the microenvironment of the stem cells, including the role of microRNAs and extracellular vesicles.

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The efficacy of systemic corticosteroids in community-acquired pneumonia (CAP) has not yet been confirmed. We prospectively investigated the clinical features of patients treated with early adjunctive systemic corticosteroids and its clinical impact in very severe CAP.

METHODS: One hundred and one consecutive CAP patients having a pneumonia severity index of >130 points were enrolled from August 2010 through February 2013. Early adjunctive systemic corticosteroids were defined as administration of systemic corticosteroids equivalent to prednisone of ≥20 mg/day added to initial antibiotics. The multivariate analysis was performed to evaluate the independent factors associated with mortality.

RESULTS: Thirty-two patients (31.7%) died within 28 days of admission. Early adjunctive systemic corticosteroids were administered in 30 patients (29.7%), who more frequently had alteration of mental status, serious respiratory failure, or underlying lung diseases and received fluoroquinolones as initial antibiotics. In most patients treated with early adjunctive systemic corticosteroids, the dosage was less than 60 mg/day of an equivalent to prednisone by bolus intravenous infusion for a period shorter than 8 days. The occurrence of adverse events did not differ between the groups. Factors independently associated with mortality were blood urea nitrogen (hazard ratio [HR] 1.02, 95% confidence interval [CI] 1.00-1.04), serum albumin (HR 0.44, 95% CI 0.22-0.86), a requirement for intensive care (HR 4.93, 95% CI 1.75-13.87), and the therapy with early adjunctive systemic corticosteroids (HR 0.29, 95% CI 0.11-0.81).

CONCLUSION: Early adjunctive systemic corticosteroids may have an effect to reduce the mortality in very severe CAP, although a larger-scale study is necessary.

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SERPINA1, α-antitrypsin (AAT) is an acute phase protein, a member of the serpin (serine protease inhibitor) super family and one of the most abundant protease inhibitors in the circulation. The clinical importance of AAT is emphasized in persons with inherited AAT deficiency who exhibit high risk of developing early onset pulmonary emphysema, neonatal hepatitis, liver cirrhosis, which may appear at any age, and in rare cases panniculitis and vasculitis.

The most common and severe AAT deficiency is associated with the Z (Glu342 to Lys) mutation. It is also well established that Z AAT deficiency results from the polymerization and accumulation of the misfolded AAT protein. Consequently, low levels of circulating Z AAT are assumed to be inadequate to neutralize elastolytic activity and to prevent lung tissue damage. Novel studies, however, are expanding the link between AAT and human diseases. Associations are shown between reduced AAT levels and HIV type 1 infection, hepatitis C infection, diabetes mellitus, vasculitis, panniculitis and other diseases. Given the importance of the protease/antiprotease imbalance in causing emphysema, augmentation of circulating AAT is used as a specific therapy for patients with AAT deficiency-related emphysema but not for those with liver diseases.

According to the novel findings, therapy with AAT possesses antiinflammatory and immuno-modulatory effects across a broad spectrum of experimental models of systemic and local inflammation. Hence, in this article we will discuss putative new directions for the clinical use of therapy with AAT.

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Salbutamol, as a short-acting β2-agonist, was popularly used in the past for detection of reversibility in patients with airway obstruction when it was the only drug available in the treatment of airway obstruction. Today, the combination of long-acting β2-agonists (LABA) and inhaled glucocorticoids are the first choice of therapy, with or without the presence of reversibility, in patients with airway obstruction. We aimed to compare the efficacy of salbutamol and long acting β2-agonists plus inhaled glucocorticoids for early reversibility test in patients with airway obstruction.

METHODS: Symptomatic patients (cough, dyspnea, and/or wheezing) with airway obstruction according to pulmonary function testing (FEV1/FVC value less than 70% of expected) who had never used bronchodilators before or had not received short- or long-acting inhaled bronchodilator therapy within the most recent 12 hours were evaluated. Reversibility measurements were made by administering the combination of long-acting β2-agonists (LABA) and inhaled glucocorticoids after 15 minutes.

RESULTS: A total of 90 patients were evaluated. The mean age of patients was 57.3±17.7 (range, 8-88) years and the male-to-female ratio was 69/21. The baseline pulmonary function test results were mean FVC; 2,747±1,181 mL and 74.7%±21.4%, mean FEV1; 1,716±825 mL and 57.5%±19.0%, mean FEV1/FVC; 61.4%±7.4%. The bronchodilator drugs given before reversibility testing were as salmeterol/fluticasone (FTC/SAL), formoterol/budesonide (BUD/FOR), beclomethasone dipropionate/formoterol (BDP/FOR) and salbutamol (SLB) in 24, 22, 24 and 20 patients, respectively. The reversibility was positive in 33 (36.7%) patients. The absolute change and percentage of change in mean FEV1 were 206±252 mL, 13.2%±16.6% for FTC/SAL group, 273±201 mL, 14%±8% for BUD/FOR group, 240±151 mL, 18.7%±15.9% for BUD/FOR groupand 171±116 mL, 13.3%±11.8% for SLB group. There was no statistically significant for reversibilty results between LABAs/inhaledsteroids and SLB group. And the patients with positivere versibility test were significantly higher in both of BUD/FOR and BDP/FOR groups than SLB group.

CONCLUSIONS: We think that performance of an early reversibility test using the combination of a LABA and an inhaled corticosteroid for treatment would enhance both the education of the patient in using the device and the reliability of the drug. And, we suggest that: "you should make the reversibility test with Long-Acting β2-Agonists plus Inhaled Corticosteroids which used in treatment of obstructive lung diseases".

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