H1N1 Influenza Pneumonia Research Articles

Non-Cystic Fibrosis-Related Bronchiectasis in Children: Are Bacteria Always to Blame?

Background: Bronchiectasis isa structural alteration characterized by the dilation of bronchial walls due to inflammation, resulting in a loss of elasticity and muscle function. They are more common in adults than children and have various etiologies (such as chronic infections, particularly in developing countries, or immunodeficiencies in industrialized nations), with up to 40% being idiopathic. Case presentation: We reported the case of a nine-year-old child who, following two lower respiratory tract infections (a severe H1N1 influenza pneumonia and a milder episode caused by M. pneumoniae), developed bronchiectasis without underlying predisposing conditions. Discussion: Bronchiectasis is a morphological alteration of the bronchi, which can develop subsequently to lung infections and may remain clinically silent even for a long time. The most common associated symptoms include productive cough, persistent rales, therapy-resistant “asthma,” and recurrent lung infections. High-Resolution CT (HRCT) scans are the gold standard for their diagnosis, while their management requires a comprehensive approach, including pharmacological and psychosocial measures. It is always advisable to investigate the underlying etiology to eventually establish a causal treatment. Conclusion: This study aims to emphasize that not only bacteria but also viral infections and their associated inflammatory impact on lung tissue can contribute to the development of bronchiectasis. This study aims to implement current knowledge regarding non-cystic fibrosis-related bronchiectasis and to underscore the significance of post-acute instrumental reassessment in lower respiratory tract infections, especially when severe.

Using a targeted metabolomics approach to explore differences in ARDS associated with COVID-19 compared to ARDS caused by H1N1 influenza and bacterial pneumonia

RationaleAcute respiratory distress syndrome (ARDS) is a life-threatening critical care syndrome commonly associated with infections such as COVID-19, influenza, and bacterial pneumonia. Ongoing research aims to improve our understanding of ARDS, including its molecular mechanisms, individualized treatment options, and potential interventions to reduce inflammation and promote lung repair.ObjectiveTo map and compare metabolic phenotypes of different infectious causes of ARDS to better understand the metabolic pathways involved in the underlying pathogenesis.MethodsWe analyzed metabolic phenotypes of 3 ARDS cohorts caused by COVID-19, H1N1 influenza, and bacterial pneumonia compared to non-ARDS COVID-19-infected patients and ICU-ventilated controls. Targeted metabolomics was performed on plasma samples from a total of 150 patients using quantitative LC–MS/MS and DI-MS/MS analytical platforms.ResultsDistinct metabolic phenotypes were detected between different infectious causes of ARDS. There were metabolomics differences between ARDSs associated with COVID-19 and H1N1, which include metabolic pathways involving taurine and hypotaurine, pyruvate, TCA cycle metabolites, lysine, and glycerophospholipids. ARDSs associated with bacterial pneumonia and COVID-19 differed in the metabolism of D-glutamine and D-glutamate, arginine, proline, histidine, and pyruvate. The metabolic profile of COVID-19 ARDS (C19/A) patients admitted to the ICU differed from COVID-19 pneumonia (C19/P) patients who were not admitted to the ICU in metabolisms of phenylalanine, tryptophan, lysine, and tyrosine. Metabolomics analysis revealed significant differences between C19/A, H1N1/A, and PNA/A vs ICU-ventilated controls, reflecting potentially different disease mechanisms.ConclusionDifferent metabolic phenotypes characterize ARDS associated with different viral and bacterial infections.

COVID-19 and H1N1 Influenza: Are They 2 Sides of the Same Coin?

Swine flu (H1N1) and Coronavirus diseases (COVID-19) have been compared in the past few months. Both pandemics sparked a worldwide major panic. Although both have some common symptoms and diagnoses, they are quite different in many aspects. The current study aimed to investigate the differences in clinical and viral behaviors between H1N1 Influenza and COVID-19 pneumonia. This was a retrospective study of adult patients hospitalized with H1N1 influenza pneumonia between January 2019 and February 2020, and patients hospitalized with COVID-19 during the outbreak. A demographic and clinical characteristic of H1N1 influenza and COVID-19 patients were recorded. Both groups were compared-using an independent samples student t test for continuous variables and a chi-square test for categorical data-to identify significantly different parameters between the 2 diseases. A total of 78 patients were included and divided into 2 groups: 33 patients (42.3%) with H1N1 and 45 patients (57.7%) with COVID-19. The mean age of the patients was 43.3 ± 10.6 years. Bronchial asthma was significantly higher among patients with H1N1, while diabetes mellitus was significantly higher among patients with COVID-19. Right lower lobe affection was significantly present among those with H1N1 than those with COVID (100% vs 0%). The monocytic count was significantly higher among those with H1N1 than COVID-19 (11.63 ± 1.50 vs 7.76 ± 1.68; P < 0.001). Respiratory rates of more than 22 c/min significantly increased in patients with HINI than in those with COVID-19 (18.2% vs 4.4%; P = 0.05). Mortality increased in patients with HINI than in those with COVID-19 (18.2% vs 6.7%). However, the difference did not reach statistical significance (P = 0.15). Clinically, it is difficult to distinguish between H1N1 and COVID-19. Thus, a polymerase chain reaction is recommended for all patients suffering from influenza-like symptoms to rule out influenza A subtype H1N1 and/or SARS-CoV2.

Feasibility of Radiomics to Differentiate Coronavirus Disease 2019 (COVID-19) from H1N1 Influenza Pneumonia on Chest Computed Tomography: A Proof of Concept.

Background: Chest computed tomography (CT) plays an essential role in diagnosing coronavirus disease 2019 (COVID-19). However, CT findings are often nonspecific among different viral pneumonia conditions. The differentiation between COVID-19 and influenza can be challenging when seasonal influenza concurs with the COVID-19 pandemic. This study was conducted to test the ability of radiomics-artificial intelligence (AI) to perform this task.Methods: In this retrospective study, chest CT images from 47 patients with COVID-19 (after February 2020) and 19 patients with H1N1 influenza (before September 2019) pneumonia were collected from three hospitals affiliated with Arak University of Medical Sciences, Arak, Iran. All pulmonary lesions were segmented on CT images. Multiple radiomics features were extracted from the lesions and used to develop support-vector machine (SVM), k-nearest neighbor (k-NN), decision tree, neural network, adaptive boosting (AdaBoost), and random forest.Results: The patients with COVID-19 and H1N1 influenza were not significantly different in age and sex (P=0.13 and 0.99, respectively). Nonetheless, the average time between initial symptoms/hospitalization and chest CT was shorter in the patients with COVID-19 (P=0.001 and 0.01, respectively). After the implementation of the inclusion and exclusion criteria, 453 pulmonary lesions were included in this study. On the harmonized features, random forest yielded the highest performance (area under the curve=0.97, sensitivity=89%, precision=90%, F1 score=89%, and classification accuracy=89%).Conclusion: In our preliminary study, radiomics feature extraction, conjoined with AI, especially random forest and neural network, appeared to yield very promising results in the differentiation between COVID-19 and H1N1 influenza on chest CT.

Pulmonary Thromboembolism and Pulmonary Fibrosis due to H1N1 Pneumonia with Acute Respiratory Distress Syndrome :: Not ALL is COVID

Novel influenza A H1N1 virus (pH1N1) was the predominant strain in the 2009 pandemic. It continues to circulate along with other influenza strains in the post pandemic era. This new virus is nevertheless well known for its strong association with high cardiovascular mortality and a high propensity to preferentially affect young and otherwise healthy adults, resulting in a clustering of severe and even fatal cases in patients of the productive age group. H1N1 infection is a multifaceted disease. It affects the lung parenchyma as well as the pulmonary vasculature. It also affects the multisystemic vasculature and can cause other embolic events not strictly falling in the “usual” thrombotic category. We herein present a case of H1N1 influenza pneumonia induced severe ARDS with pulmonary thromboembolism (PTE) and pulmonary fibrosis.

Comparison of Clinical Characteristics and Outcomes Between COVID-19 Pneumonia and H1N1 Influenza

The COVID-19 pandemic has been likened to the 2009 H1N1 influenza pandemic. We aim to study the similarities and differences between patients hospitalized with COVID-19 and H1N1 influenza in order to provide better care to patients, particularly during the co-circulation of Influenza A Subtype H1N1 and SARS-CoV-2. A retrospective cohort study was conducted in order to compare clinical characteristics, complications, and outcomes of hospitalized patients with PCR-confirmed H1N1 influenza pneumonia and COVID-19 at a tertiary care center in Karachi, Pakistan. A total of 115 patients hospitalized with COVID-19 were compared with 55 patients with H1N1 Influenza A pneumonia. Median age was similar in both COVID-19 patients (54 years) and in patients with H1N1 influenza (59 years), but there was male predominance in COVID-19 patients (OR = 2.95; 95% CI: 1.12-7.79). Patients with COVID-19 pneumonia were 1.34 (95% CI: 1.14-1.62) times more likely to have a greater duration of illness prior to presentation compared to H1N1 influenza patients. COVID-19 patients were 4.59 times (95% CI: 1.32-15.94) more likely to be admitted to a general ward compared to H1N1 pneumonia patients. Moreover, patients with COVID-19 were 7.62 times (95% CI: 2.42-24.00) more likely to be treated with systemic steroids compared to patients with H1N1 pneumonia. The rate of nosocomial infections as well as mortality was similar in both H1N1 and COVID-19 pneumonia. Our study found a male predominance and longer duration of illness in hospitalized patients with COVID-19 compared to H1N1 influenza patients but no difference in outcomes with either infection.

Validation of pneumonia prognostic scores in a statewide cohort of hospitalised patients with COVID‐19

ObjectiveWe aimed to externally validate the predictive performance of two recently developed COVID‐19‐specific prognostic tools, the COVID‐GRAM and CALL scores, and prior prognostic scores for community‐acquired pneumonia (CURB‐65), viral pneumonia (MuBLSTA) and H1N1 influenza pneumonia (Influenza risk score) in a contemporary US cohort.MethodsWe included 257 hospitalised patients with laboratory‐confirmed COVID‐19 pneumonia from three teaching hospitals in Rhode Island. We extracted data from within the first 24 hours of admission. Variables were excluded if values were missing in >20% of cases, otherwise, missing values were imputed. One hundred and fifteen patients with complete data after imputation were used for the primary analysis. Sensitivity analysis was performed after the exclusion of one variable (LDH) in the complete dataset (n = 257). Primary and secondary outcomes were in‐hospital mortality and critical illness (mechanical ventilation or death), respectively.ResultsOnly the areas under the receiver‐operating characteristic curves (RO‐AUC) of COVID‐GRAM (RO‐AUC = 0.775, 95% CI 0.525‐0.915) for in‐hospital death, and CURB65 for in‐hospital death (RO‐AUC = 0.842, 95% CI 0.674‐0.932) or critical illness (RO‐AUC = 0.766, 95% CI 0.584‐0.884) were significantly better than random. Sensitivity analysis yielded similar trends. Calibration plots showed better agreement between the estimated and observed probability of in‐hospital death for CURB65, compared with COVID‐GRAM. The negative predictive value (NPV) of CURB65 ≥2 was 97.2% for in‐hospital death and 88.1% for critical illness.ConclusionsThe COVID‐GRAM score demonstrated acceptable predictive performance for in‐hospital death. The CURB65 score had better prognostic utility for in‐hospital death and critical illness. The high NPV of CURB65 values ≥2 may be useful in triaging and allocation of resources.

Clinical characteristics and outcomes of patients with H1N1 influenza pneumonia admitted at a tertiary care hospital in Karachi, Pakistan

IntroductionInfluenza viruses specifically, A and B mainly contribute to seasonal outbreaks that occur globally. However, due to limited diagnostics for influenza there is little data regarding clinical outcomes of patients with H1N1 pneumonia in our region. Our objective was to determine the clinical characteristics and outcomes of patients hospitalized with H1N1 pneumonia at a tertiary care facility in Karachi, Pakistan.MethodsA retrospective study of adult patients admitted with influenza pneumonia from November 2017 to February 2018 at a tertiary care hospital in Karachi, Pakistan. Patient characteristics were compared between influenza A H1N1 and other types of influenza using multivariable logistic regression analysis and subgroup analysis for factors associated with mortality in H1N1 Pneumonia was performed.ResultsOut of 497 adult patients with community acquired pneumonia (CAP), 172 fulfilled the criteria for Influenza like illness (ILI). 88 patients had PCR confirmed Influenza pneumonia of whom n = 57 (65%) had Influenza A H1N1. The mean age of patients 53.5 years (SD: 17.3) and 60% were male. The overall mortality from Influenza in this study was 15.9% (n = 14); out of these 11 (78.5%) had Influenza A H1N1. Multivariable analysis showed that the increase in length of hospital admission was significantly associated with H1N1 Influenza A infection (OR: 1.47 CI: 1.2–1.8). Factors associated with mortality showed that presence of ARDS, Septic shock and multi-organ failure was highly significantly associated with death (p-value < 0.001) along with deranged liver function tests (p-value 0.01) and presence of nosocomial infection (p-value 0.027).ConclusionInfluenza A H1N1 is associated with greater length of stay compared with infection due to other types of Influenza and mortality in H1N1 Pneumonia was found to be associated with presence of nosocomial infection among several other factors which may have implications given higher rates in a low-middle income country.

Improved survival rates in patients with H1N1 acute respiratory failure in Korea between 2009 and 2016.

There was a pandemic of influenza A (H1N1) in 2009; in Korea, there was also an H1N1 epidemic in 2016. We aim to investigate whether survival had improved in the setting of recent advances in intensive care unit (ICU) management. We conducted a retrospective analysis of acute respiratory failure patients with H1N1 influenza pneumonia in 2016 and 2009 respectively at two tertiary referral hospitals in Korea. A total of 28 patients were treated in 2016, and 34 in 2009. There was no significant difference in SOFA scores on ICU admission day. In-hospital mortality was significantly lower in patients of 2016 compared to those of 2009 (18% vs. 44% P = 0.028). By multivariable analyses, the treatment year 2016 was associated with a greater likelihood of survival. Compared to the patients treated in 2009, those treated in 2016 were one seventh as likely to die after adjusting for other clinical variables (hazard ratio for mortality, 0.15; 95% confidence interval. 0.03–0.63, P = 0.010). Improved survival in patients who underwent extracorporeal membrane oxygenation treatment (in-hospital mortality, 17% vs. 60%, P = 0.242) and decreased tidal volumes during mechanical ventilation (median 5.4 mL/kg vs. median 9.2 mL/kg, P = 0.018) were observed in 2016 compared to 2009. Treatment outcomes for patients with H1N1 acute respiratory failure improved from 2009 to 2016 in two tertiary referral centers in South Korea.

Outcomes of severe H1N1 pneumoniae: A retrospective study at intensive care units

The incidence of acute respiratory distress syndrome (ARDS) and the mortality rate of H1N1 influenza pneumonia are unclear. The aim of this study is to investigate the clinical features and outcomes of adult patients admitted to intensive care units (ICUs) with H1N1 pneumonia related ARDS. This retrospective study included patients with confirmed H1N1 influenza pneumonia admitted to the ICUs of a medical center between July 2009 and May 2014. We investigated the patients' characteristics, clinical presentations, illness severities, and outcomes. Sixty-six patients were confirmed to have H1N1 influenza pneumonia requiring mechanical ventilation. Fifty-four of those patients (82%) developed ARDS, while their hospital mortality rate was 33% (22/66). There were no significant differences in the ICU and hospital mortality rates of the ARDS and non-ARDS patients. Among the ARDS patients, there were higher rates of solid malignant disease (22.8% vs. 2.8%, p=0.038) and sepsis (66.7% vs. 33.3%, p=0.020) and a higher mean tidal volume (8.9±1.8 vs. 7.8±1.9ml/kg, p=0.032) in the non-survivors than the survivors. Logistic regression analysis revealed that a high tidal volume (odds ratio=1.448, 95 % CI=1.033-2.030; p=0.032) and sequential organ failure assessment (SOFA) score (odds ratio=1.233, 95% CI=1.029-1.478; p=0.023) were the risk factors of hospital mortality. For H1N1 influenza pneumonia patients admitted to ICUs with mechanical ventilation, there is a high probability of developing ARDS with a modest mortality rate. For patients with ARDS due to H1N1 influenza pneumonia, the tidal volume and SOFA score are the predictors of hospital mortality.

First-in-human phase 1 study of the BTK inhibitor GDC-0853 in relapsed or refractory B-cell NHL and CLL

GDC-0853 is a selective, reversible, and non-covalent inhibitor of Bruton’s tyrosine kinase (BTK) that does not require interaction with the Cys481 residue for activity. In this first-in-human phase 1 study we evaluated safety, tolerability, pharmacokinetics, and activity of GDC-0853 in patients with relapsed or refractory non-Hodgkin lymphoma (NHL) or chronic lymphocytic leukemia (CLL). Twenty-four patients, enrolled into 3 cohorts, including 6 patients who were positive for the C481S mutation, received GDC-0853 at 100, 200, or 400 mg once daily, orally. There were no dose limiting toxicities. GDC-0853 was well tolerated and the maximum tolerated dose (MTD) was not reached due to premature study closure. Common adverse events (AEs) in ≥ 15% of patients regardless of causality included fatigue (37%), nausea (33%), diarrhea (29%), thrombocytopenia (25%), headache (20%), and abdominal pain, cough, and dizziness (16%, each). Nine serious AEs were reported in 5 patients of whom 2 had fatal outcomes (confirmed H1N1 influenza and influenza pneumonia). A third death was due to progressive disease. Eight of 24 patients responded to GDC-0853: 1 complete response, 4 partial responses, and 3 partial responses with lymphocytosis, including 1 patient with the C481S mutation. Two additional C481S mutation patients had a decrease in size of target tumors (–23% and –44%). These data demonstrate GDC-0853 was generally well-tolerated with antitumor activity.

Inhibitory effects and related molecular mechanisms of total flavonoids in Mosla chinensis Maxim against H1N1 influenza virus.

The Shixiangru (Mosla chinensis Maxim) total flavonoids (STF) mainly contain luteolin and apigenin. The study aims to examine the inhibitory effects of STF on anti-H1N1 influenza virus and its related molecular mechanisms in pneumonia mice. The viral pneumonia mice were treated with Ribavirin or various doses of STF. We observed histological changes of lung by immunohistochemistry and measured lung index to value anti-influenza virus effects of STF. The concentrations of inflammatory cytokines and anti-oxidant factors were detected by ELISA. RT-PCR and western blot assays were used to determine the expression level of TLR pathway's key genes and proteins in lung tissues. We found that the pathological changes of lung in the viral pneumonia mice obviously alleviated by STF treatments and the STF (288 or 576mg/kg) could significantly decrease lung indices. Moreover, the up-regulation (IL-6, TNF-α, IFN-γ, and NO) and down-regulation (IL-2, SOD and GSH) of inflammatory cytokines and anti-oxidant factors were associated with higher clearance of virus and reduction of inflammatory lung tissue damage. Meanwhile, the expression levels of TLR3, TLR7, MyD88, TRAF3 and NF-κB p65 of the TLR pathway were reduced by STF treatment. This study suggested that STF may be a promising candidate for treating H1N1 influenza and subsequent viral pneumonia.

Plasma metabolomics for the diagnosis and prognosis of H1N1 influenza pneumonia

BackgroundMetabolomics is a tool that has been used for the diagnosis and prognosis of specific diseases. The purpose of this study was to examine if metabolomics could be used as a potential diagnostic and prognostic tool for H1N1 pneumonia. Our hypothesis was that metabolomics can potentially be used early for the diagnosis and prognosis of H1N1 influenza pneumonia.Methods1H nuclear magnetic resonance spectroscopy and gas chromatography-mass spectrometry were used to profile the metabolome in 42 patients with H1N1 pneumonia, 31 ventilated control subjects in the intensive care unit (ICU), and 30 culture-positive plasma samples from patients with bacterial community-acquired pneumonia drawn within the first 24 h of hospital admission for diagnosis and prognosis of disease.ResultsWe found that plasma-based metabolomics from samples taken within 24 h of hospital admission can be used to discriminate H1N1 pneumonia from bacterial pneumonia and nonsurvivors from survivors of H1N1 pneumonia. Moreover, metabolomics is a highly sensitive and specific tool for the 90-day prognosis of mortality in H1N1 pneumonia.ConclusionsThis study demonstrates that H1N1 pneumonia can create a quite different plasma metabolic profile from bacterial culture-positive pneumonia and ventilated control subjects in the ICU on the basis of plasma samples taken within 24 h of hospital/ICU admission, early in the course of disease.

Radiological findings in patients with H1N1 influenza pneumonia

BackgroundA new strain of human influenza A (H1N1) virus originated from Mexico in 2009 and spread to more than 190 countries. WHO declared it a level 6 (highest level) pandemic. Some previously healthy patients who were infected by H1N1 virus experienced rapidly progressive pneumonia leading to acute respiratory distress syndrome (ARDS) and even death. The aim of this study was to describe the radiological features in adult patients with H1N1 influenza pneumonia and to see if there were any predominant radiological features. MethodsRetrospective descriptive study was performed during the epidemic of H1N1 influenza infection from August through November 2009 in two Middle East countries. The study involved 209 adult patients with laboratory confirmed H1N1 influenza virus infection by RT-PCR. Pneumonia was confirmed in 54 patients of them. The CXR (No. 54) and the chest CT images (No. 24) of those 54 patients were enrolled in the study for radiological description. ResultsMean age of patients was 43.07years, of them 27 patients were males. CXR was diagnostic of pneumonia in 47/54 patients and chest CT was diagnostic of pneumonia in 24/24 patients. GGO (34/47 of CXR and 23/24 of CT) and alveolar consolidation (31/47 of CXR and 16/24 of CT) were the predominant pattern. Chest CT was more sensitive than the CXR in the diagnosis (17/24 for CXR and 24/24 for CT) and in showing the different patterns of opacities (p value was 0.02 for alveolar opacity and was 0.00 for both GGO and nodular opacity). The opacities were mainly bilateral (28/47 of CXR and 17/24 of CT), basal and midzonal in CXR (23/47), and peripheral (23/24) in CT. Most of the cases were not extensive (33/47 of CXR and 18/24 of CT). ConclusionThe predominant radiological pattern in H1N1 pneumonia is bilateral GGO and alveolar consolidation. In the CXR, the opacities were basal and midzonal while in the chest CT were peripheral and peribronchovascular with diffuse zonal involvement. Chest CT is more sensitive than CXR in diagnosing doubtful cases and in showing different patterns of opacities.

Proteomics study of N‐acetylcysteine response in H1N1‐infected cells by using mass spectrometry

The pathology of A/Puerto Rico/8/1934 (H1N1) infection associated with the interaction of virus and its host cells is not clear. N-Acetylcysteine (NAC) is an antioxidant as well as a premier antitoxin and immune support substance. A high dose of NAC was recently reported for a therapy of H1N1 (2009) influenza pneumonia. NAC was used as a small-molecule organic probe to investigate the protein expression of human lung carcinoma cell line (A549) infected by influenza virus A/Puerto Rico/8/1934 (H1N1). Differential proteins were identified from MALDI-TOF MS and Q-TOF MS/MS analyses. The obtained results showed that NAC kept cells away from apoptosis. Virus-infected cells were arrested in G0/G1 phase. The lowest cell population of G0/G1 phase was detected when the cells were treated by 10 mM NAC for one day. Application of MS-based proteomics allowed the identification of the differential proteins. Software analysis showed that four proteins had close relationship. The results indicated that NAC as a small-molecule probe might effect the protein expression of A549 cells infected by the H1N1 virus.

Procalcitonin for diagnosis of bacterial pneumonia in critically ill patients during 2009 H1N1 influenza pandemic: a prospective cohort study, systematic review and individual patient data meta-analysis

IntroductionProcalcitonin (PCT) is helpful for diagnosing bacterial infections. The diagnostic utility of PCT has not been examined thoroughly in critically ill patients with suspected H1N1 influenza.MethodsClinical characteristics and PCT were prospectively assessed in 46 patients with pneumonia admitted to medical ICUs during the 2009 and 2010 influenza seasons. An individual patient data meta-analysis was performed by combining our data with data from five other studies on the diagnostic utility of PCT in ICU patients with suspected 2009 pandemic influenza A(H1N1) virus infection identified by performing a systematic literature search.ResultsPCT levels, measured within 24 hours of ICU admission, were significantly elevated in patients with bacterial pneumonia (isolated or coinfection with H1N1; n = 77) (median = 6.2 μg/L, interquartile range (IQR) = 0.9 to 20) than in patients with isolated H1N1 influenza pneumonia (n = 84; median = 0.56 μg/L, IQR = 0.18 to 3.33). The area under the curve of the receiver operating characteristic curve of PCT was 0.72 (95% confidence interval (CI) = 0.64 to 0.80; P < 0.0001) for diagnosis of bacterial pneumonia, but increased to 0.76 (95% CI = 0.68 to 0.85; P < 0.0001) when patients with hospital-acquired pneumonia and immune-compromising disorders were excluded. PCT at a cut-off of 0.5 μg/L had a sensitivity (95% CI) and a negative predictive value of 80.5% (69.9 to 88.7) and 73.2% (59.7 to 84.2) for diagnosis of bacterial pneumonia, respectively, which increased to 85.5% (73.3 to 93.5) and 82.2% (68.0 to 92.0) in patients without hospital acquired pneumonia or immune-compromising disorder.ConclusionsIn critically ill patients with pneumonia during the influenza season, PCT is a reasonably accurate marker for detection of bacterial pneumonia, particularly in patients with community-acquired disease and without immune-compromising disorders, but it might not be sufficient as a stand-alone marker for withholding antibiotic treatment.

IFITM3 and Susceptibility to Respiratory Viral Infections in the Community

Interferon-inducible transmembrane proteins 1, 2, and 3 (IFITM 1,2, and 3) are viral restriction factors that mediate cellular resistance to several viruses. We have genotyped a possible splice-site altering single-nucleotide polymorphism (rs12252) in the IFITM3 gene in 34 patients with H1N1 influenza and severe pneumonia, and >5000 individuals comprising patients with community-acquired mild lower respiratory tract infection and matched controls of Caucasian ancestry. We found evidence of an association between rs12252 rare allele homozygotes and susceptibility to mild influenza (in patients attending primary care) but could not confirm a previously reported association between this single-nucleotide polymorphism and susceptibility to severe H1N1 infection.

Designing and conducting a randomized trial for pandemic critical illness: the 2009 H1N1 influenza pandemic

To analyze the hurdles in implementing a randomized trial of corticosteroids for severe 2009 H1N1 influenza infections. This was an investigator-led, multicenter, randomized, placebo-controlled, double-blind trial of corticosteroids in ICU patients with 2009 H1N1 influenza pneumonia requiring mechanical ventilation. The feasibility of and hurdles in designing and initiating a phase III trial in a short-lived pandemic crisis were analyzed. The regulatory agency and ethics committee approved the study's scientific, financial, and ethical aspects within 4 weeks. Hydrocortisone and placebo were prepared centrally and shipped to participating hospitals within 6 weeks. The inclusion period started on November 9, 2009. From August 1, 2009 to March 8, 2010, only 205/224 ICU patients with H1N1 infections required mechanical ventilation. The peak of the wave was missed by 2-3 weeks and only 26 patients were randomized. The two main reasons for non-inclusion were patients' admission before the beginning of the trial and ICU personnel overwhelmed by clinical duties. Parallel rather than sequential regulatory and ethics approval, and preparation and masking of study drugs by local pharmacists would have allowed the study to start 1 month earlier and before the peak of the "flu" wave. A dedicated research team in each participating center would have increased the ratio of screened to randomized patients. This report highlights the main hurdles in implementing a randomized trial for a pandemic critical illness and proposes solutions for future trials.

Cytokine Response in Pediatric Patients with Pandemic H1N1 Influenza Virus Infection and Pneumonia: Comparison with Pediatric Pneumonia Without H1N1 Infection

Cytokine Response in Pediatric Patients with Pandemic H1N1 Influenza Virus Infection and Pneumonia: Comparison with Pediatric Pneumonia Without H1N1 Infection

Predicting mortality in hospitalized patients with 2009 H1N1 influenza pneumonia

Community-acquired pneumonia (CAP) severity scores can identify patients at low risk for mortality who may be suitable for ambulatory care. Here, we follow the clinical course of hospitalized patients with CAP due to 2009 H1N1 influenza. To evaluate the role of CAP severity scores as predictors of mortality. This was a secondary data analysis of patients hospitalized with CAP due to 2009 H1N1 influenza confirmed by reverse transcriptase polymerase chain reaction enrolled in the CAPO (Community-Acquired Pneumonia Organization) international cohort study. CAP severity scores PSI (Pneumonia Severity Index), CURB-65 (confusion, urea, respiratory rate, blood pressure, age ≥ 65 years) and CRB-65 (confusion, respiratory rate, blood pressure, age ≥ 65 years) were calculated. Actual and predicted mortality rates were compared. A total of 37 predictor variables were evaluated to define those associated with mortality. Data from 250 patients with CAP due to 2009 H1N1 influenza were analyzed. Patients with low predicted mortality rates (0-1.5%) had actual mortality rates ranging from 2.6% to 17.5%. Obesity and wheezing were the only novel variables associated with mortality. The decision to hospitalize a patient with CAP due to 2009 H1N1 influenza should not be based on current CAP severity scores, as they underestimate mortality rates in a significant number of patients. Patients with obesity or wheezing should be considered at an increased risk for mortality.