Severe respiratory insufficiency during pandemic H1N1 infection: prognostic value and therapeutic potential of pulmonary surfactant protein A.
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ABSTRACT:
SUBMITTER: Tolosa MF
PROVIDER: S-EPMC4423634 | biostudies-literature | 2014 Aug
REPOSITORIES: biostudies-literature
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Project description:INTRODUCTION: Inherited variability in host immune responses influences susceptibility and outcome of Influenza A virus (IAV) infection, but these factors remain largely unknown. Components of the innate immune response may be crucial in the first days of the infection. The collectins surfactant protein (SP)-A1, -A2, and -D and mannose-binding lectin (MBL) neutralize IAV infectivity, although only SP-A2 can establish an efficient neutralization of poorly glycosylated pandemic IAV strains. METHODS: We studied the role of polymorphic variants at the genes of MBL (MBL2), SP-A1 (SFTPA1), SP-A2 (SFTPA2), and SP-D (SFTPD) in 93 patients with H1N1 pandemic 2009 (H1N1pdm) infection. RESULTS: Multivariate analysis showed that two frequent SFTPA2 missense alleles (rs1965708-C and rs1059046-A) and the SFTPA2 haplotype 1A(0) were associated with a need for mechanical ventilation, acute respiratory failure, and acute respiratory distress syndrome. The SFTPA2 haplotype 1A(1) was a protective variant. Kaplan-Meier analysis and Cox regression also showed that diplotypes not containing the 1A(1) haplotype were associated with a significantly shorter time to ICU admission in hospitalized patients. In addition, rs1965708-C (P = 0.0007), rs1059046-A (P = 0.0007), and haplotype 1A(0) (P = 0.0004) were associated, in a dose-dependent fashion, with lower PaO2/FiO2 ratio, whereas haplotype 1A(1) was associated with a higher PaO2/FiO2 ratio (P = 0.001). CONCLUSIONS: Our data suggest an effect of genetic variants of SFTPA2 on the severity of H1N1pdm infection and could pave the way for a potential treatment with haplotype-specific (1A(1)) SP-A2 for future IAV pandemics.
| S-EPMC4229788 | biostudies-literature
Project description:The differentiation between influenza and coronavirus disease 2019 (COVID-19) could constitute a diagnostic challenge during the ongoing winter owing to their clinical similitude. Thus, novel biomarkers are required to enable making this distinction. Here, we evaluated whether the surfactant protein D (SP-D), a collectin produced at the alveolar epithelium with known immune properties, was useful to differentiate pandemic influenza A(H1N1) from COVID-19 in critically ill patients. Our results revealed high serum SP-D levels in patients with severe pandemic influenza but not those with COVID-19. This finding was validated in a separate cohort of mechanically ventilated patients with COVID-19 who also showed low plasma SP-D levels. However, plasma SP-D levels did not distinguish seasonal influenza from COVID-19 in mild-to-moderate disease. Finally, we found that high serum SP-D levels were associated with death and renal failure among severe pandemic influenza cases. Thus, our studies have identified SP-D as a unique biomarker expressed during severe pandemic influenza but not COVID-19.
| S-EPMC7989215 | biostudies-literature
Project description:The influenza A (H1N1)pdm09 outbreak in 2009 exemplified the problems accompanying the emergence of novel influenza A virus (IAV) strains and their unanticipated virulence in populations with no pre-existing immunity. Neuraminidase inhibitors (NAIs) are currently the drugs of choice for intervention against IAV outbreaks, but there are concerns that NAI-resistant viruses can transmit to high-risk populations. These issues highlight the need for new approaches that address the annual influenza burden. In this study, we examined whether palmitoyl-oleoyl-phosphatidylglycerol (POPG) and phosphatidylinositol (PI) effectively antagonize (H1N1)pdm09 infection. POPG and PI markedly suppressed cytopathic effects and attenuated viral gene expression in (H1N1)pdm09-infected Madin-Darby canine kidney cells. POPG and PI bound to (H1N1)pdm09 with high affinity and disrupted viral spread from infected to noninfected cells in tissue culture and also reduced (H1N1)pdm09 propagation by a factor of 102 after viral infection was established in vitro In a mouse infection model of (H1N1)pdm09, POPG and PI significantly reduced lung inflammation and viral burden. Of note, when mice were challenged with a typically lethal dose of 1000 plaque-forming units of (H1N1)pdm09, survival after 10 days was 100% (14 of 14 mice) with the POPG treatment compared with 0% (0 of 14 mice) without this treatment. POPG also significantly reduced inflammatory infiltrates and the viral burden induced by (H1N1)pdm09 infection in a ferret model. These findings indicate that anionic phospholipids potently and efficiently disrupt influenza infections in animal models.
| S-EPMC7008372 | biostudies-literature
Project description:Pandemic influenza viruses often cause severe disease in middle-aged adults without preexisting comorbidities. The mechanism of illness associated with severe disease in this age group is not well understood. Here we find preexisting serum antibodies that cross-react with, but do not protect against, 2009 H1N1 influenza virus in middle-aged adults. Nonprotective antibody is associated with immune complex-mediated disease after infection. We detected high titers of serum antibody of low avidity for H1-2009 antigen, and low-avidity pulmonary immune complexes against the same protein, in severely ill individuals. Moreover, C4d deposition--a marker of complement activation mediated by immune complexes--was present in lung sections of fatal cases. Archived lung sections from middle-aged adults with confirmed fatal influenza 1957 H2N2 infection revealed a similar mechanism of illness. These observations provide a previously unknown biological mechanism for the unusual age distribution of severe cases during influenza pandemics.
| S-EPMC3034774 | biostudies-other
Project description:The 2009 H1N1 influenza A virus that has targeted not only those with chronic medical illness, the very young and old, but also a large segment of the patient population that has previously been afforded relative protection - those who are young, generally healthy, and immune naive. The illness is mild in most, but results in hospitalization and severe ARDS in an important minority. Among those who become critically ill, 20-40% will die, predominantly of severe hypoxic respiratory failure. However, and potentially in part due to the young age of those affected, intensive care with aggressive oxygenation support will allow most people to recover. The volume of patients infected and with critical illness placed substantial strain on the capacity of the health care system and critical care most specifically. Despite this, the 2009 pandemic has engaged our specialty and highlighted its importance like no other. Thus far, the national and global critical care response has been brisk, collaborative and helpful - not only for this pandemic, but for subsequent challenges in years ahead.
| S-EPMC3256529 | biostudies-other
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.
| S-EPMC9295393 | biostudies-literature
Project description:PurposeIn view of the expected 2009 influenza A(H1N1) pandemic, the Italian Health Authorities set up a national referral network of selected intensive care units (ICU) able to provide advanced respiratory care up to extracorporeal membrane oxygenation (ECMO) for patients with acute respiratory distress syndrome (ARDS). We describe the organization and results of the network, known as ECMOnet.MethodsThe network consisted of 14 ICUs with ECMO capability and a national call center. The network was set up to centralize all severe patients to the ECMOnet centers assuring safe transfer. An ad hoc committee defined criteria for both patient transfer and ECMO institutions.ResultsBetween August 2009 and March 2010, 153 critically ill patients (53% referred from other hospitals) were admitted to the ECMOnet ICU with suspected H1N1. Sixty patients (48 of the referred patients, 49 with confirmed H1N1 diagnosis) received ECMO according to ECMOnet criteria. All referred patients were successfully transferred to the ECMOnet centers; 28 were transferred while on ECMO. Survival to hospital discharge in patients receiving ECMO was 68%. Survival of patients receiving ECMO within 7 days from the onset of mechanical ventilation was 77%. The length of mechanical ventilation prior to ECMO was an independent predictor of mortality.ConclusionsA network organization based on preemptive patient centralization allowed a high survival rate and provided effective and safe referral of patients with severe H1N1-suspected ARDS.
| S-EPMC7080128 | biostudies-literature
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.
| S-EPMC6088209 | biostudies-literature
Project description:Data on risk factors for severe outcomes from 2009 pandemic influenza A (H1N1) virus infection are limited outside of developed countries.We reviewed medical charts to collect data from patients hospitalized with laboratory-confirmed 2009 H1N1 infection who were identified across China during the period from September 2009 through February 2010, and we analyzed potential risk factors associated with severe illness (defined as illness requiring intensive care unit admission or resulting in death).Among 9966 case patients, the prevalence of chronic medical conditions (33% vs 14%), pregnancy (15% vs 7%), or obesity (19% vs 14%) was significantly higher in those patients with severe illness than it was in those with less severe disease. In multivariable analyses, among nonpregnant case patients aged ? 2 years, having a chronic medical condition significantly increased the risk of severe outcome among all age groups, and obesity was a risk factor among those <60 years of age. The risk of severe illness among pregnant case patients was significantly higher for those in the second and third trimesters. The risk of severe illness was increased when oseltamivir treatment was initiated ? 5 days after illness onset (odds ratio, 1.42; 95% confidence interval, 1.20-1.67). For persons <60 years of age, the prevalence of obesity among case patients with severe illness was significantly greater than it was among those without severe illness or among the general population.Risk factors for severe 2009 H1N1 illness in China were similar to those observed in developed countries, but there was a lower prevalence of chronic medical conditions and a lower prevalence of obesity. Obesity was a risk factor among case patients < 60 years of age. Early initiation of oseltamivir treatment was most beneficial, and there was an increased risk of severe disease when treatment was started ? 5 days after illness onset.
| S-EPMC3060897 | biostudies-other
Project description:This case-control study was carried out to estimate risk factors associated with hospitalizations and severe outcomes [intensive care unit (ICU) admission or death] among patients with illness because of laboratory-confirmed 2009 pandemic A/H1N1 virus (pH1N1) during the first wave of pH1N1 activity in the province of Quebec, Canada.We collected epidemiologic information by phone using a standardized questionnaire from patients with laboratory-confirmed pH1N1 illness during the first spring/summer pandemic wave in Quebec, Canada. Risk factors associated with hospitalization were assessed by comparing hospitalized to community cases and for ICU admission or death through comparison with hospitalized cases.Cases (321 hospitalized patients including 47 ICU admissions and 15 deaths) were compared to controls (395 non-hospitalized patients) by using multivariable logistic regression adjusted for gender, age, education, being a health care worker, smoking, seasonal influenza vaccination, delay to consultation, antiviral use before admission, pregnancy, underlying medical conditions, and obesity. Age <5 years, underlying medical conditions (neuromuscular, cardiac, pulmonary, and renal conditions, diabetes, asthma, and other), and delayed consultation were associated with hospitalization. The strongest association with hospitalization was observed for neuromuscular disorders. Antiviral medication before hospital admission protected against severe disease. Association of obesity with hospitalization was not significant after adjustment in multivariable analysis. Among hospitalized patients, age ≥60 years and immune suppression were associated with death.Previously identified risk factors for seasonal influenza were also associated with increased risk of severe pH1N1 outcomes. The independent role of obesity needs to be further defined.
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