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Severe respiratory insufficiency during pandemic H1N1 infection: prognostic value and therapeutic potential of pulmonary surfactant protein A.

ABSTRACT: For almost two decades, studies have shown collectins to be critical for effective antimicrobial defense of the airways. Members of this protein family, which includes surfactant proteins (SP)-A and D, provide broad-spectrum protection through promoting the aggregation and clearance of pathogens. Interestingly, these proteins may also modulate the immune response, and growing evidence has shown collectins to be protective against several markers of inflammation and injury. In a recent study by Herrera-Ramos and colleagues, genetic variants of collectins were examined in Spanish patients with the pandemic 2009 H1N1 influenza A virus. Comparing genotypes for measures of poor lung function, inflammation, and admission to intensive care, these authors identified three variants of the SP-A gene SFTPA2 that positively correlated with flu severity. Remarkably, they also found the haplotype 1A(1) of SFTPA2 to be protective against these indicators, suggesting that targeted therapy with a recombinant form of SP-A2 may improve patient outcome. Although further work is required to confirm the specificity and efficacy of SP-A in therapeutic H1N1 protection, this study is one of the first to suggest a clinical role for SP-A in pandemic influenza.

SUBMITTER: Tolosa MF

PROVIDER: S-EPMC4423634 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Severe respiratory insufficiency during pandemic H1N1 infection: prognostic value and therapeutic potential of pulmonary surfactant protein A.

Tolosa Monica Fern MF Palaniyar Nades N

Critical care (London, England) 20140807 4

For almost two decades, studies have shown collectins to be critical for effective antimicrobial defense of the airways. Members of this protein family, which includes surfactant proteins (SP)-A and D, provide broad-spectrum protection through promoting the aggregation and clearance of pathogens. Interestingly, these proteins may also modulate the immune response, and growing evidence has shown collectins to be protective against several markers of inflammation and injury. In a recent study by H ...[more]

PMID: 25184962

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Project description:BackgroundLong-term home non-invasive ventilation (LTH-NIV) has an impact on the health-related quality of life of patients with chronic hypercapnic respiratory failure (CRF) of different causes. There are generic and specific questionnaires for respiratory diseases. In 2003 a specific questionnaire was developed for patients with CRF in LTH-NIV, called the Severe Respiratory Insufficiency (SRI) questionnaire, which has been shown to be reproducible and reliable and has been validated in several languages. The aim of the study was to translate and culturally adapt the SRI questionnaire for adult Chilean patients under LTH-NIV, and to assess its psychometric properties.MethodsThe Chilean version of the SRI was obtained using the translation-back translation method, which was then applied by cross-sectional study to a non-probabilistic convenience sample of stable patients from five regions of Chile. The validated Chilean version of the SRI questionnaire and SF-36 (gold standard) questionnaire were applied, demographic and ventilatory data were collected. Reliability was analysed using Cronbach's alpha and intraclass correlation (test-retest). Construct validity was tested using exploratory factor analysis (principal component extraction and equimax orthogonal rotation) and hypothesis testing (Mann-Whitney test). Convergent criterion validity was tested using Spearman's rho.ResultsThe sample comprised 248 patients, 132 women (53.2%), median age (IQR) was 62 years (51-75), 146 patients (58.9%) were 60 years or older, 40% had a low education level. The mean ± SD completion time of the questionnaire was 18.8 ± 9.1 min, and 100% of the items were answered. The questionnaire was self-applied by 46.8% of the sample. The validated Chilean version of the SRI questionnaire showed very good overall reliability (0.95) and by scales (> 0.7). It showed a good correlation with the SF-36, with equivalent scales, a rotated matrix with 8 factors and hypotheses that explain the underlying constructs.ConclusionsThe validated Chilean version of the SRI questionnaire has good psychometric properties. It is feasible, valid, and reliable for application to evaluate patients with CRF in LTH-NIV. It was found to be sensitive to assess the characteristics of the local population.

Project description:Surfactant protein D (SP-D) is a pattern recognition molecule belonging to the Collectin (collagen-containing C-type lectin) family that has pulmonary as well as extra-pulmonary existence. In the lungs, it is a well-established opsonin that can agglutinate a range of microbes, and enhance their clearance via phagocytosis and super-oxidative burst. It can interfere with allergen-IgE interaction and suppress basophil and mast cell activation. However, it is now becoming evident that SP-D is likely to be an innate immune surveillance molecule against tumor development. SP-D has been shown to induce apoptosis in sensitized eosinophils derived from allergic patients and a leukemic cell line via p53 pathway. Recently, SP-D has been shown to suppress lung cancer progression via interference with the epidermal growth factor signaling. In addition, a truncated form of recombinant human SP-D has been reported to induce apoptosis in pancreatic adenocarcinoma via Fas-mediated pathway in a p53-independent manner. To further establish a correlation between SP-D presence/levels and normal and cancer tissues, we performed a bioinformatics analysis, using Oncomine dataset and the survival analysis platforms Kaplan-Meier plotter, to assess if SP-D can serve as a potential prognostic marker for human lung cancer, in addition to human gastric, breast, and ovarian cancers. We also analyzed immunohistochemically the presence of SP-D in normal and tumor human tissues. We conclude that (1) in the lung, gastric, and breast cancers, there is a lower expression of SP-D than normal tissues; (2) in ovarian cancer, there is a higher expression of SP-D than normal tissue; and (3) in lung cancer, the presence of SP-D could be associated with a favorable prognosis. On the contrary, at non-pulmonary sites such as gastric, breast, and ovarian cancers, the presence of SP-D could be associated with unfavorable prognosis. Correlation between the levels of SP-D and overall survival requires further investigation. Our analysis involves a large number of dataset; therefore, any trend observed is reliable. Despite apparent complexity within the results, it is evident that cancer tissues that produce less levels of SP-D compared to their normal tissue counterparts are probably less susceptible to SP-D-mediated immune surveillance mechanisms via infiltrating immune cells.

Dataset Information

Severe respiratory insufficiency during pandemic H1N1 infection: prognostic value and therapeutic potential of pulmonary surfactant protein A.

Publications

Severe respiratory insufficiency during pandemic H1N1 infection: prognostic value and therapeutic potential of pulmonary surfactant protein A.

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