Regenerative pulmonary medicine: potential and promise, pitfalls and challenges.

Eur J Clin Invest. 2012 Feb 28;

Authors: Anversa P, Perrella MA, Kourembanas S, Choi AM, Loscalzo J

Abstract
Eur J Clin Invest 2012 ABSTRACT: Background  Chronic lung diseases contribute significantly to the morbidity and mortality of the population. There are few effective treatments for many chronic lung diseases, and even fewer therapies that can arrest or reverse the progress of the disease. Design  In this review, we present the current state of regenerative therapies for the treatment of chronic lung diseases. We focus on endothelial progenitor cells, mesenchymal stem cells, and endogenous lung stem/progenitor cells; summarize the work to date in models of lung diseases for each of these therapies; and consider their potential benefits and risks as viable therapies for patients with lung diseases. Conclusions  Cell-based regenerative therapies for lung diseases offer great promise, with preclinical studies suggesting that the next decade should provide the evidence necessary for their ultimate application to our therapeutic armamentarium.

PMID: 22435680 [PubMed - as supplied by publisher]

Adjunctive surgery improves treatment outcomes among patients with multidrug-resistant and extensively drug-resistant tuberculosis.

Int J Infect Dis. 2012 Mar 17;

Authors: Gegia M, Kalandadze I, Kempker RR, Magee MJ, Blumberg HM

Abstract
OBJECTIVES: To determine risk factors for poor outcomes among patients with pulmonary multidrug- or extensively drug-resistant (M/XDR) tuberculosis (TB) in Georgia. METHODS: This was a prospective, population-based observational cohort study. RESULTS: Among 380M/XDR-TB patients (mean age 38 years), 179 (47%) had a poor outcome: 59 (16%) died, 37 (10%) failed, and 83 (22%) defaulted. Newly diagnosed M/XDR-TB cases were significantly more likely to have a favorable outcome than retreatment cases (odds ratio (OR) 4.26, 95% confidence interval (CI) 1.99-9.10, p<0.001). In the multivariable analysis, independent risk factors for a poor treatment outcome included previous treatment history (OR 2.92, 95% CI 1.29-6.58), bilateral disease (OR 1.90, 95% CI 1.20-3.01), body mass index (BMI, kg/m(2)) ≤18.5 (OR 1.91, 95% CI 1.11-3.29), and XDR-TB (OR 2.28, 95% CI 1.11-4.71). Patients who underwent surgical resection (OR 0.27, 95% CI 0.11-0.64) and had sputum culture conversion by 4 months (OR 0.33, 95% CI 0.21-0.52) were significantly less likely to have poor treatment outcomes. CONCLUSIONS: Adjunctive surgery appeared to be beneficial in treating patients with M/XDR-TB. Retreatment cases, XDR-TB, bilateral disease, and low BMI were associated with a poor outcome. Additional studies are needed to further define the apparent beneficial role of surgery in the treatment of M/XDR-TB.

PMID: 22425494 [PubMed - as supplied by publisher]

[Place of surgery in pulmonary aspergillosis and other pulmonary mycotic infections].

Rev Pneumol Clin. 2012 Apr;68(2):67-76

Authors: Pagès PB, Abou Hanna H, Caillot D, Bernard A

Abstract
Surgery is part of the therapeutic strategy of aspergillosis and mucormycosis. The aspergilloma is defined as a rounded mass, developing in a cavity by the proliferation of spores of Aspergillus. The most common complication was haemoptysis reported in 50-95% of cases. The pleuropulmonary lesions predisposing are: tuberculosis, residual pleural space, emphysema and lung destroyed by fibrosis or radiotherapy or bronchiectasis. The indications for surgery depend on symptoms, respiratory function, the parenchyma and the type of aspergilloma (simple or complex). In a patient with an intrapulmonary aspergilloma, lung resection preceded by embolization is recommended based on respiratory function. For intrapleural aspergilloma, thoracoplasty is recommended according to the patient's general condition. The invasive pulmonary aspergillosis (IPA) is characterized by an invasion of lung tissue and blood vessels by hyphae in immunocompromised patients. The death rate of patients who have an API after treatment for leukemia or lymphoma was 30 to 40%, after bone marrow transplantation 60%, after solid organ transplantation from 50 to 60% and after any other cause of immunocompromising from 70 to 85%. The main cause of these deaths is massive hemoptysis. Surgery (lobectomy) is indicated for the prevention of hemoptysis when the mass is in contact with the pulmonary artery or one of its branches, and if it increases in size with the disappearance of border security between the mass and the vessel wall. The patient will be operated in an emergency before the white blood cells do not exceed the threshold of 1000cells/μl. A persistent residual mass after antifungal treatment may justify a lung resection (lobectomy or wedge) before a new aggressive therapy. Mucormycosis affects patients following immunocompromising states - haematologic malignancy, diabetes mellitus, transplantation, burns and malnutrition. The treatment of pulmonary mucormycosis combines surgical and medical approach.

PMID: 22425505 [PubMed - in process]

Interferon-gamma release assay performance in pulmonary and extrapulmonary tuberculosis.

PLoS One. 2012;7(3):e32652

Authors: Feng Y, Diao N, Shao L, Wu J, Zhang S, Jin J, Wang F, Weng X, Zhang Y, Zhang W

Abstract
BACKGROUND: The diagnosis of tuberculosis remains difficult. This study aimed to assess performance of interferon-gamma release assay (IGRA) in diagnosis of active tuberculosis (ATB) with pulmonary and extrapulmonary involvements, and to determine the diagnostic role of IGRA (T-SPOT.TB) and tuberculin skin test (TST) in BCG-vaccinated population.
METHODS AND FINDINGS: Two hundred twenty-six ATB suspects were recruited and examined with T-SPOT.TB. Among them, fifty-two and seventy-six subjects were simultaneously tested by TST with 5TU or 1TU of purified protein derivative (PPD). The sensitivity of T-SPOT.TB was 94.7% (71/75), comparable in pulmonary and extrapulmonary disease groups (95.6% vs. 93.3%, P>0.05), while the specificity was 84.10% (90/107) but differed in two groups (69.2% vs. 88.9%, P = 0.02). Compared to T-SPOT.TB, TST with 5TU-PPD showed less sensitivity (92.3% vs. 56.4%) and specificity (84.6% vs. 61.5%) (both P<0.01); the sensitivity of TST with 1TU-PPD was 27.8%, and despite its specificity identical to T-SPOT.TB (both 82.8%) positive predictive value (PPV) was only 33.3%. By combining T-SPOT.TB with TST (1TU), the specificity rose to 95%, but the PPV stayed unchanged.
CONCLUSIONS: IGRA could function as a powerful immunodiagnostic test to explore pulmonary and extrapulmonary TB, while TST failed to play a reliable or auxiliary role in identifying TB disease and infection in the BCG-vaccinated population.

PMID: 22427859 [PubMed - in process]