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Steroids in severe pneumonia: a literature review

Despite more than sixty years of scientific medical research, severe pneumonia, either community-acquired or nosocomial, remains a leading cause of death regardless of the patients’ immunity state.

The clinical introduction of new and more potent antibiotic molecules and the continuous development of efficient respiratory assistance devices may not be able to radically improve the clinical outcome of pneumonia. Adjunctive therapies based on the physiopathological mechanisms of lung damage in severe pneumonia have been strongly advocated, and corticosteroids, which present many properties that theoretically interfere with these pathways, have been widely used, with conflicting results.

The aim of this review is to examine existing literature data on steroid use in severe pneumonia. Molecular, endocrinological and clinical studies will be described to help physicians to clarify the reasons for the historical debate about steroid use as an adjunctive treatment in severe pneumonia. There is growing evidence that, during lung infection, an excessive inflammatory response can have deleterious effects and contribute to tissue damage mechanisms. Because of their immunomodulatory properties, glucocorticoids have been suggested as a useful tool for regulating the complex balance of cytokine networks, and they are commonly used as an adjunctive therapy during serious infections. In severe pneumonia, preclinical data, including cytokine level detection and animal studies, have shown encouraging results, although the clinical data is controversial. Moreover, large randomized controlled trials have not been conducted to determine steroid side effects and the risk of immunosuppression-induced superinfections.

The benefits of steroid use in patients with severe pneumonia have not been proven by current literature, but ongoing investigations of anti-inflammatory molecules probably represent the key point of severe infection management in the near future.

Systemic biomarkers in exacerbations of COPD: the evolving clinical challenge

Exacerbations of chronic obstructive pulmonary disease (ECOPD) remain a major cause of mortality and morbidity of COPD patients. Despite advances in the understanding of their pathophysiology, their assessment relies primarily on clinical presentation which can be variable and difficult to predict. A large number of biomarkers have already been assessed in this context and some appear to be promising.

Methods: An online search for articles published until December 2010 was conducted using 3 terms for ECOPD, 5 terms for biomarkers and 5 terms regarding the sampling method. Biomarkers were evaluated for their potential role in the establishment and/or confirmation of the diagnosis of ECOPD, the evaluation of etiology and severity, the prediction of prognosis and the guidance of treatment decisions.

Results: Several systemic biomarkers have been measured in the context of ECOPD and most of them have been found to increase at ECOPD onset and to subside during the course of exacerbations. Correlations have been reported among these biomarkers but direct associations with clinical variables have been more difficult to establish. Although there are several limitations yet to be addressed, some of the biomarkers, and most notably C-reactive protein for the identification of a COPD exacerbation and procalcitonin for antibiotic guidance, may provide clinically relevant information.

Conclusions: So far no single biomarker has been able to gain wide acceptance, but some provide clinically useful information. The evaluation of such biomarkers in large decision-making studies is expected to become an area of intense investigation in the near future.

Azithromycin for Prevention of Exacerbations of COPD

Background

Acute exacerbations adversely affect patients with chronic obstructive pulmonary disease (COPD). Macrolide antibiotics benefit patients with a variety of inflammatory airway diseases.

Methods

We performed a randomized trial to determine whether azithromycin decreased the frequency of exacerbations in participants with COPD who had an increased risk of exacerbations but no hearing impairment, resting tachycardia, or apparent risk of prolongation of the corrected QT interval.

Results

A total of 1577 subjects were screened; 1142 (72%) were randomly assigned to receive azithromycin, at a dose of 250 mg daily (570 participants), or placebo (572 participants) for 1 year in addition to their usual care. The rate of 1-year follow-up was 89% in the azithromycin group and 90% in the placebo group. The median time to the first exacerbation was 266 days (95% confidence interval [CI], 227 to 313) among participants receiving azithromycin, as compared with 174 days (95% CI, 143 to 215) among participants receiving placebo (P<0.001). The frequency of exacerbations was 1.48 exacerbations per patient-year in the azithromycin group, as compared with 1.83 per patient-year in the placebo group (P=0.01), and the hazard ratio for having an acute exacerbation of COPD per patient-year in the azithromycin group was 0.73 (95% CI, 0.63 to 0.84; P<0.001). The scores on the St. George's Respiratory Questionnaire (on a scale of 0 to 100, with lower scores indicating better functioning) improved more in the azithromycin group than in the placebo group (a mean [±SD] decrease of 2.8±12.8 vs. 0.6±11.4, P=0.004); the percentage of participants with more than the minimal clinically important difference of −4 units was 43% in the azithromycin group, as compared with 36% in the placebo group (P=0.03). Hearing decrements were more common in the azithromycin group than in the placebo group (25% vs. 20%, P=0.04).

Conclusions

Among selected subjects with COPD, azithromycin taken daily for 1 year, when added to usual treatment, decreased the frequency of exacerbations and improved quality of life but caused hearing decrements in a small percentage of subjects. Although this intervention could change microbial resistance patterns, the effect of this change is not known. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00325897.)

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Magnetic resonance imaging for lung cancer detection: Experience in a population of more than 10,000 healthy individuals.

BACKGROUND: Recent refinements of lung MRI techniques have reduced the examination time and improved diagnostic sensitivity and specificity. We conducted a study to assess the feasibility of MRI for the detection of primary lung cancer in asymptomatic individuals.

METHODS: A retrospective chart review was performed on images of lung parenchyma, which were extracted from whole-body MRI examinations between October 2000 and December 2007. 11,766 consecutive healthy individuals (mean age, 50.4 years; 56.8% male) were scanned using one of two 1.5-T scanners (Sonata and Sonata Maestro, Siemens Medical Solutions, Erlangen, Germany). The standard protocol included a quick whole-lung survey with T2-weighted 2-dimensional half Fourier acquisition single shot turbo spin echo (HASTE) and 3-dimensional volumetric interpolated breath-hold examination (VIBE). Total examination time was less than 10 minutes, and scanning time was only 5 minutes. Prompt referrals and follow-ups were arranged in cases of suspicious lung nodules.

RESULTS: A total of 559 individuals (4.8%) had suspicious lung nodules. A total of 49 primary lung cancers were diagnosed in 46 individuals: 41 prevalence cancers and 8 incidence cancers. The overall detection rate of primary lung cancers was 0.4%. For smokers aged 51 to 70 years, the detection rate was 1.4%. TNM stage I disease accounted for 37 (75.5%). The mean size of detected lung cancers was 1.98 cm (median, 1.5 cm; range, 0.5-8.2 cm). The most histological types were adenocarcinoma in 38 (77.6%).

CONCLUSION: Rapid zero-dose MRI can be used for lung cancer detection in a healthy population.

Multicenter Analysis of Survival and Prognostic Factors in Pathologic Stage I Non-Small-Cell Lung Cancer According to the New 2009 TNM Classification.

INTRODUCTION: The new 2009 TNM classification introduced important modifications in lung cancer staging. The aim of this study is to validate our series of patients with pathologic stage I non-small-cell lung cancer according to the 7th edition of the TNM classification of malignant tumors and to the factors related with prognosis.

PATIENTS AND METHODS: A multicenter retrospective study was performed. Survival rates were calculated by the Kaplan-Meier method, and for multivariate analyses, Cox proportional hazards regression model was used. The following variables were analyzed: age, sex, pathologic stage, T category, histology, type of resection and tumor size.

RESULTS: A total of 402 patients were included. Mean follow-up was 70.18 months. Overall 5-year survival was 68%. Males and patients over 70 had lower survival. Prognosis worsened with increasing pathologic stage, T category and tumor size. We found no statistically significant differences in prognosis for histology or type of resection. Multivariate analysis showed age, sex and pathologic stage to be independent prognostic factors.

CONCLUSIONS: Survival results and the analysis of prognostic factors in our series are similar to those published in the new 2009 TNM classification. The most important prognostic factor is pathologic stage. Other adverse prognostic factors include male sex and age over 70.

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