IFITM3 and severe influenza virus infection. No evidence of genetic association.

Influenza virus infection (IVI) is typically subclinical or causes a self-limiting upper respiratory disease. However, in a small subset of patients IVI rapidly progresses to primary viral pneumonia (PVP) with respiratory failure; a minority of patients require intensive care unit admission. Inherited and acquired variability in host immune responses may influence susceptibility and outcome of IVI. However, the molecular basis of such human factors remains largely elusive. It has been proposed that homozygosity for IFITM3 rs12252-C is associated with a population-attributable risk of 5.4 % for severe IVI in Northern Europeans and 54.3 % for severe H1N1pdm infection in Chinese. A total of 148 patients with confirmed IVI were considered for recruitment; 118 Spanish patients (60 of them hospitalized with PVP) and 246 healthy Spanish individuals were finally included in the statistical analysis. PCR-RFLP was used with confirmation by Sanger sequencing. The allele frequency for rs12252-C was found to be 3.5 % among the general Spanish population. We found no rs12252-C homozygous individuals in our control group. The only Spanish patient homozygous for rs12252-C had a neurological disorder (a known risk factor for severe IVI) and mild influenza. Our data do not suggest a role of rs12252-C in the development of severe IVI in our population. These data may be relevant to recognize whether patients homozygous for rs12252-C are at risk of severe influenza, and hence require individualized measures in the case of IVI.

Solitary tumours associated with Jaagsiekte retrovirus in sheep are heterogeneous and contain cells expressing markers identifying progenitor cells in lung repair.

Ovine pulmonary adenocarcinoma (OPA) is a naturally occurring lung cancer of sheep caused by jaagsiekte sheep retrovirus (JSRV). This study examines immunohistochemically solitary lung nodules considered as early OPA lesions from 11 sheep infected naturally by JSRV. All 11 neoplastic nodules exhibited features of adenocarcinoma and in four of them mesenchymal growth was also observed. Both types of lesion were labelled with antibody specific for JSRV-Env. In two cases infiltrating lymphoreticular cells also contained JSRV-Env. All tumours had a high Ki67 labelling index and variably contained cells expressing CC10 (a marker of Clara cells (CCs)), SPC (a marker of type II pneumocytes), p63 and keratin 14 (markers for stem/progenitor cells of the lung airway epithelia). Tumours with mesenchymal growth had intense expression of vimentin and desmin, weak expression of smooth muscle actin and did not express pancytokeratin and p63. Both epithelial and mesenchymal proliferations did not express the stem cell markers CD90 and CD117, but some tumour infiltrating cells expressed CD133. Solitary OPA tumours can therefore be adenocarcinomas or mixed tumours and have a heterogeneous cellular composition, containing groups of cells expressing markers that characterize local progenitor cells involved in lung repair.

Initial management of pneumonia and sepsis: factors associated with improved outcome.

Processes of care and adherence to guidelines have been associated with improved survival in community-acquired pneumonia (CAP). In sepsis, bundles of processes of care have also increased survival. We aimed to audit compliance with guideline-recommended processes of care and its impact on outcome in hospitalised CAP patients with sepsis. We prospectively studied 4,137 patients hospitalised with CAP in 13 hospitals. The processes of care evaluated were adherence to antibiotic prescription guidelines, first dose within 6 h and oxygen assessment. Outcome measures were mortality and length of stay (LOS). Oxygen assessment was measured in 3,745 (90.5%) patients; 3,024 (73.1%) patients received antibiotics according to guidelines and 3,053 (73.8%) received antibiotics within 6 h. In CAP patients with sepsis, the strongest independent factor for survival was antibiotic adherence (OR 0.4). In severe sepsis, only compliance to antibiotic adherence plus first dose within 6 h was associated with lower mortality (OR 0.60), adjusted for fine prognostic scale and hospital. Antibiotic adherence was related to shorter hospital stay. In sepsis, antibiotic adherence is the strongest protective factor of care associated with survival and LOS. In severe sepsis, combined antibiotic adherence and first dose within 6 h may reduce mortality.

Impact of initial antibiotic choice on mortality from pneumococcal pneumonia.

To determine the impact of initial antimicrobial choice on 30-day mortality rate in patients with community-acquired pneumonia due to Streptococcus pneumoniae (CAP-SP), a prospective, observational study was conducted in 35 Spanish hospitals. A total of 638 patients with CAP-SP were identified. Antimicrobials were chosen by the attending physician. Patients were grouped into the following categories: beta-lactam monotherapy (n = 251), macrolide monotherapy (n = 37), beta-lactam plus macrolide (n = 198), levofloxacin alone/combination (n = 48), and other combinations (n = 104). The reference category was beta-lactam+macrolide. The 30-day survival probability was 84.9%. Using multivariate survival analysis, factors related to mortality in the entire population were: bilateral disease, suspected aspiration, shock, HIV infection, renal failure and pneumonia severity index (PSI) score Class IV versus I-III and categories V versus I-III. The association of beta-lactams+macrolides was not better than the use of beta-lactams alone. The current authors analysed the different groups of patients with significant mortality/morbidity: intensive care unit, PSI Class >III, renal failure, chronic lung disease and bacteraemia. Only in patients with PSI Class >III, who had undergone initial antimicrobial choice classified as other combinations, were associated with higher mortality. In conclusion, the current authors have not demonstrated an independent association between initial antimicrobial regimen and 30-day mortality in community-acquired pneumococcal pneumonia patients, except for those with a higher pneumonia severity index score.

Risk factors of treatment failure in community acquired pneumonia: implications for disease outcome.

BACKGROUND: An inadequate response to initial empirical treatment of community acquired pneumonia (CAP) represents a challenge for clinicians and requires early identification and intervention. A study was undertaken to quantify the incidence of failure of empirical treatment in CAP, to identify risk factors for treatment failure, and to determine the implications of treatment failure on the outcome. METHODS: A prospective multicentre cohort study was performed in 1424 hospitalised patients from 15 hospitals. Early treatment failure (<72 hours), late treatment failure, and in-hospital mortality were recorded. RESULTS: Treatment failure occurred in 215 patients (15.1%): 134 early failure (62.3%) and 81 late failure (37.7%). The causes were infectious in 86 patients (40%), non-infectious in 34 (15.8%), and undetermined in 95. The independent risk factors associated with treatment failure in a stepwise logistic regression analysis were liver disease, pneumonia risk class, leucopenia, multilobar CAP, pleural effusion, and radiological signs of cavitation. Independent factors associated with a lower risk of treatment failure were influenza vaccination, initial treatment with fluoroquinolones, and chronic obstructive pulmonary disease (COPD). Mortality was significantly higher in patients with treatment failure (25% v 2%). Failure of empirical treatment increased the mortality of CAP 11-fold after adjustment for risk class. CONCLUSIONS: Although these findings need to be confirmed by randomised studies, they suggest possible interventions to decrease mortality due to CAP.

Community-acquired pneumonia in the elderly: Spanish multicentre study.

Community-acquired pneumonia (CAP) in the elderly has increased as a consequence of an overall increase of the elderly population. A controversy about the aetiology and outcome of CAP in this population still exists and more epidemiological studies are needed. A prospective, 12-month, multicentre study was carried out to assess the clinical characteristics, aetiology, evolution and prognostic factors of elderly patients (> or = 65 yrs) admitted to hospital for CAP. The study included 503 patients (age 76 +/- 7 yrs). The clinical picture lasted < or = 5 days in 318 (63%) and the main clinical features were cough (n = 407, 81%) and fever (n = 380, 76%). Aetiological diagnosis was achieved in 199 (40%) cases, with a definite diagnosis obtained in 164 (33%). Of the 223 microorganisms isolated the main agents found were Streptococcus pneumoniae in 98 (49%) and Haemophilus influenzae in 27 (14%). A total of 53 patients died (11%) and the multivariate analysis showed the following factors of bad prognosis: previous bed confinement, alteration in mental status, absence of chills, plasma creatinine > or = 1.4 mg x dL(-1), oxygen tension in arterial blood/inspiratorv oxygen fraction ratio < 200 at the time of admission, and shock and renal failure during the evolution. The results of this study may aid in the management of empiric antibiotic treatment in elderly patients with community-acquired pneumonia and the patients who have a greater probability of bad evolution may be identified based on the risk factors.

Lack of effects of moderate-high altitude upon lung function in healthy middle-aged volunteers.

This study investigates the effects of moderate-high altitude on lung function and exercise performance in 46 volunteers (19 females, 27 males), with a mean age of 42.4 +/- 1.4 years (+/- SEM) and varying smoking and exercise habits, who were not previously acclimatized. Measures obtained in the base camp (1140 m) and at altitude (2630 m), in random order, included forced spirometry, maximal voluntary ventilation, maximal inspiratory and expiratory pressures, arterial oxygen saturation and capillary lactate concentration after a standardized exercise test. The smoking history, Fagerström test and degree of habitual physical activity were also recorded for each participant. The percentage of smokers was similar in males (19%) and females (21%) (P = n.s.). Mean habitual physical activity index was 8.2 +/- 0.2 (range, 5.88-11.63). At the base camp, all lung function variables were within the normal range. Lactate concentration after exercise averaged 3.7 +/- 0.3 mm l-1. No significant change was observed at altitude, except for a higher heart rate and a lower arterial oxygen saturation (SaO2) (both at rest and after inspiratory manoeuvres). The smoking history and the degree of physical activity did not influence lung function or exercise performance at altitude. The results of this study show that in middle-aged, healthy, not particularly well-trained individuals, lung function is not significantly altered by moderate-high altitude, despite the absence of any acclimatization period and independent of their smoking history and previous exercise habits.

[Endobronchial tuberculosis]. / Tuberculosis endobronquial.

Eight hospitalized patients with endobronchial tuberculosis are reported. Diagnosis was reached in six patients by the demonstration of acid-alcohol resistant bacilli in the bronchial aspirate. In the fifth patient microscopic examination of the bacteria in the liquid obtained by aspiration of a paraspinal abscess was positive. In the last patient diagnosis was established by the positive growth in Lowenstein's medium of lymph node extracts. The clinical, radiologic, endoscopic and microbiologic features are discussed.