Epidemiological and clinical data of hospitalizations associated with respiratory syncytial virus infection in children under 5 years of age in Spain: FIVE multicenter study.

BACKGROUND Respiratory syncytial virus (RSV) is an important pathogen in lower respiratory tract infections (LRTI) in infants, but there are limited data concerning patients with underlying conditions and children older than 2 years of age. METHODS We have designed a prospective observational multicenter national study performed in 26 Spanish hospitals (December 2011-March 2012). Investigational cases were defined as children with underlying chronic diseases and were compared with a group of previously healthy children (proportion 1:2). Clinical data were compared between the groups. RESULTS A total of 1763 children hospitalized due to RSV infection during the inclusion period were analyzed. Of them, 225 cases and 460 healthy children were enrolled in the study. Underlying diseases observed were respiratory (64%), cardiovascular (25%), and neurologic (12%), as well as chromosomal abnormalities (7·5%), immunodeficiencies (6·7%), and inborn errors of metabolism (3·5%). Cases were statistically older than previously healthy children (average age: 16·3 versus 5·5 months). Cases experienced hypoxemia more frequently (P < 0·001), but patients with respiratory diseases required oxygen therapy more often (OR: 2·99; 95% CI: 1·03-8·65). Mechanical ventilation was used more in patients with cardiac diseases (OR: 3·0; 95% CI: 1·07-8·44) and in those with inborn errors of metabolism (OR: 12·27; 95% CI: 2·11-71·47). This subgroup showed a higher risk of admission to the PICU (OR: 6·7, 95% CI: 1·18-38·04). Diagnosis of pneumonia was more frequently found in cases (18·2% versus 9·3%; P < 0·01). CONCLUSIONS A significant percentage of children with RSV infection have underlying diseases and the illness severity is higher than in healthy children.

Tratamiento farmacológico de la EPOC estable

Pharmacological treatment of patients with stable COPD should be individualised. Inhaled bronchodilators are the mainstay of pharmacological treatment for COPD. Long-acting medications (LABA or LAMA) are recommended over short-acting agents (SABA or SAMA). Short-acting bronchodilators are used on demand to rapidly control symptoms regardless of level of severity. Long-acting bronchodilators are used as maintenance therapy and are the mainstay of treatment in patients with permanent symptoms. Initial treatment for COPD is monotherapy with a long-acting bronchodilator. Clinical practice guidelines do not specify the best bronchodilator to use. The choice should be made on an individual basis, taking into account the patient’s preferences, response to treatment, its potential side effects and cost. When monotherapy fails to control symptoms, the first recommended step is to check medication adherence, inhaler technique and adequacy of inhalation device, and if these are correct but monotherapy is still insufficient, treatment should be intensified with combined inhaled therapies. Most clinical practice guidelines recommend the use of long-term therapy with LABA+inhaled corticosteroids in patients who experience frequent exacerbations and with FEV1 <50%. Long-term monotherapy with inhaled corticosteroids or oral corticosteroids is not recommended, and neither is the regular use of mucolytics nor the use of roflumilast.

Trends in socioeconomic inequalities in preventable mortality in urban areas of 33 Spanish cities, 1996-2007 (MEDEA project).

Abstract Background: Preventable mortality is a good indicator of possible problems to be investigated in the primary prevention chain, making it also a useful tool with which to evaluate health policies particularly public health policies. This study describes inequalities in preventable avoidable mortality in relation to socioeconomic status in small urban areas of thirty three Spanish cities, and analyses their evolution over the course of the periods 1996–2001 and 2002–2007. Methods: We analysed census tracts and all deaths occurring in the population residing in these cities from 1996 to 2007 were taken into account. The causes included in the study were lung cancer, cirrhosis, AIDS/HIV, motor vehicle traffic accidents injuries, suicide and homicide. The census tracts were classified into three groups, according their socioeconomic level. To analyse inequalities in mortality risks between the highest and lowest socioeconomic levels and over different periods, for each city and separating by sex, Poisson regression were used. Results: Preventable avoidable mortality made a significant contribution to general mortality (around 7.5%, higher among men), having decreased over time in men (12.7 in 1996–2001 and 10.9 in 2002–2007), though not so clearly among women (3.3% in 1996–2001 and 2.9% in 2002–2007). It has been observed in men that the risks of death are higher in areas of greater deprivation, and that these excesses have not modified over time. The result in women is different and differences in mortality risks by socioeconomic level could not be established in many cities. Conclusions: Preventable mortality decreased between the 1996–2001 and 2002–2007 periods, more markedly in men than in women. There were socioeconomic inequalities in mortality in most cities analysed, associating a higher risk of death with higher levels of deprivation. Inequalities have remained over the two periods analysed. This study makes it possible to identify those areas where excess preventable mortality was associated with more deprived zones. It is in these deprived zones where actions to reduce and monitor health inequalities should be put into place. Primary healthcare may play an important role in this process. Keywords: Preventable avoidable mortality, Causes of death, Inequalities in health, Small area analysis

Pandemic 2009 A(H1N1) infection requiring hospitalization of elderly Spanish adults.

To describe the clinical presentation and prognosis of elderly adults hospitalized with pandemic 2009 A(H1N1) influenza infection and to compare these data with those of younger patients. DESIGN: Prospective, observational, multicenter study. SETTING: Thirteen hospitals in Spain. PARTICIPANTS: Adults admitted to the hospital with confirmed pandemic 2009 A(H1N1) influenza infection. MEASUREMENTS: Demographic, clinical, laboratory, radiological, and outcome variables. RESULTS: Between June 12 and November 10, 2009, 585 adults with confirmed 2009 A(H1N1) influenza were hospitalized, of whom 50 (8.5%) were aged 65 and older (median age 72, range 65-87). Older adults (≥ 65) were more likely to have associated comorbidities (88.0% vs 51.2%; P < .001), primarily chronic pulmonary diseases (46.0% vs 27.3%; P < .001). Lower respiratory tract symptoms and signs such as dyspnea (60.0% vs 45.6%) and wheezing (46.0% vs 27.8%; P = .007) were also more common in these elderly adults, although pulmonary infiltrates were present in just 14 (28.0%) of the older adults, compared with 221 (41.3%) of the younger adults (P = .06). Multilobar involvement was less frequent in elderly adults with pulmonary infiltrates than younger adults with pulmonary infiltrates (21.4% vs 60.0%; P = .05). Rhinorrhea (4.0% vs 21.9%; P = .003), myalgias (42.0% vs 59.1%; P = .01), and sore throat (14.0% vs 29.2%; P = .02) were more frequent in younger adults. Early antiviral therapy (<48 hours) was similar in the two groups (34.0% vs 37.9%; P = .58). Two older adults (4.0%) died during hospitalization, compared with 11 (2.1%) younger adults (P = .30). CONCLUSION: Elderly adults with 2009 A(H1N1) influenza had fewer viral-like upper respiratory symptoms than did younger adults. Pneumonia was more frequent in younger adults. No significant differences were observed in hospital mortality.

Evaluation of the speed-oligo direct Mycobacterium tuberculosis assay for molecular detection of mycobacteria in clinical respiratory specimens.

We present the first evaluation of a novel molecular assay, the Speed-oligo Direct Mycobacterium tuberculosis (SO-DMT) assay, which is based on PCR combined with a dipstick for the detection of mycobacteria and the specific identification of M. tuberculosis complex (MTC) in respiratory specimens. A blind evaluation was carried out in two stages: first, under experimental conditions on convenience samples comprising 20 negative specimens, 44 smear- and culture-positive respiratory specimens, and 11 sputa inoculated with various mycobacterium-related organisms; and second, in the routine workflow of 566 fresh respiratory specimens (4.9% acid-fast bacillus [AFB] smear positives, 7.6% MTC positives, and 1.8% nontuberculous mycobacteria [NTM] culture positives) from two Mycobacterium laboratories. SO-DMT assay showed no reactivity in any of the mycobacterium-free specimens or in those with mycobacterium-related organisms. Compared to culture, the sensitivity in the selected smear-positive specimens was 0.91 (0.92 for MTC and 0.90 for NTM), and there was no molecular detection of NTM in a tuberculosis case or vice versa. With respect to culture and clinical data, the sensitivity, specificity, and positive and negative predictive values for the SO-DMT system in routine specimens were 0.76 (0.93 in smear positives [1.0 for MTC and 0.5 for NTM] and 0.56 in smear negatives [0.68 for MTC and 0.16 for NTM]), 0.99, 0.85 (1.00 in smear positives and 0.68 in smear negatives), and 0.97, respectively. Molecular misidentification of NTM cases occurred when testing 2 gastric aspirates from two children with clinically but not microbiologically confirmed lung tuberculosis. The SO-DMT assay appears to be a fast and easy alternative for detecting mycobacteria and differentiating MTC from NTM in smear-positive respiratory specimens.

Neutrophil defensins: their possible role in allergic asthma.

BACKGROUND Neutrophil defensins, originally identified as broad-spectrum antimicrobial peptides, have been implicated in the regulation of inflammatory and immunological processes. OBJECTIVES To investigate whether the in vitro challenge of neutrophils from patients with bronchial asthma with allergens stimulated the release of alpha-defensins and whether levels released were dependent on lung infections. METHOD The neutrophils were cultivated with different agonists and the concentration of alpha-defensin in cell-free supernatant was measured with enzyme-linked immunosorbent assay (ELISA). RESULTS Neutrophils from allergic patients released alpha-defensins via an allergen-dependent mechanism. Our results indicate that the in vitro activation of neutrophils is highly allergen-specific. In this context, allergens other than those which produced clinical symptoms did not elicit alpha-defensin release, and allergens had no effect on neutrophils from healthy donors. However, neutrophils from both allergic patients and healthy controls were able to release alpha-defensins upon treatment with PMA. In the allergen-stimulated neutrophils, cells from asthmatic patients stimulated with a sensitizing allergen showed a significantly higher production of alpha-defensin under respiratory tract infection than cells from the same patients without such an infection. CONCLUSION Neutrophils from allergic patients release alpha-defensins via an allergen-dependent mechanism.

Quality of life in patients with respiratory allergy is influenced by the causative allergen.

OBJECTIVE We aimed to analyze health-related quality of life (HRQOL) in adults with newly diagnosed respiratory allergy according to the sensitization profile for relevant aeroallergens in their usual area of residence. METHODS We performed a cross-sectional, epidemiological, observational, descriptive, multicenter study in allergy clinics in Spain. The sample comprised adults diagnosed with rhinitis, asthma, or both caused by significant allergens in their residential area (olive and/or grass pollen or house dust mite). Allergic rhinitis was classified according to the Allergic Rhinitis and its Impact on Asthma guidelines; asthma was classified according to the Guía Españiola para el Manejo del Asma (Spanish Guideline on the Management of Asthma). HRQOL was studied according to the ESPRINT-15 questionnaire and Mini Asthma Quality of Life Questionnaire. Control of asthma was measured using the Asthma Control Questionnaire 5. RESULTS We studied 1437 patients. Rhinitis was the most common respiratory disease. The HRQOL of rhinitis patients was lower in those sensitized to olive pollen only and in those with combined sensitization to olive and grass pollens. HRQOL associated with rhinitis was worse in patients diagnosed with both rhinitis and asthma than in patients diagnosed with rhinitis only. Asthma patients sensitized to olive pollen or olive and grass pollens had worse HRQOL. CONCLUSIONS In our study population, the HRQOL of patients with respiratory allergies varied with the allergen responsible for symptoms. In patients with rhinitis, the presence of asthma significantly worsened rhinitis-associated HRQOL.

Allergens Induce the Release of Lactoferrin by Neutrophils from Asthmatic Patients.

BACKGROUND Despite the evidence that Lactoferrin (Lf) is involved in allergic asthma processes, it is unknown whether neutrophils can be one of the main cellular sources of this key inflammatory mediator directly in response of an IgE mediated stimulus. The present study was undertaken to analyze this question. METHODS Neutrophils from healthy subjects (n = 34) and neutrophils from allergic asthmatic patients (n = 102) were challenged in vitro with specific allergens to which the patients were sensitized, PAF, or agonist mAbs against IgE-receptors, and the levels of Lf were measured in the culture supernatant. The levels of serum IgE together with the severity of symptoms were also analyzed. RESULTS Lf was released into the culture supernatant of neutrophils from allergic asthmatic patients in response to allergens and PAF. This response was highly allergen-specific, and did not happen in neutrophils from healthy donors. Allergen effect was mimicked by Abs against FcεRI and galectin-3 but not by FcεRII. The levels of released Lf correlated well with the levels of serum specific IgE and severity of asthma symptoms. These observations represent a novel view of neutrophils as an important source of Lf in allergic asthma. Importantly, the levels of released Lf by neutrophils could therefore be used to evaluate disease severity in allergic asthmatic patients.

Enfermedad pulmonar obstructiva crónica : proceso asistencial integrado. 3ª ed

Proceso publicado en la página web de la Consejería de Salud: www.juntadeandalucia.es/salud (Consejería de Salud / Profesionales / Nuestro Compromiso por la Calidad / Procesos Asistenciales Integrados)

A Genome-Wide Association Study of Upper Aerodigestive Tract Cancers Conducted within the INHANCE Consortium

Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p≤5×10−7). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1×10−8) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p = 2×10−8) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5×10−8; rs1229984-ADH1B, p = 7×10−9; and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.

Necrotising pneumonia due to influenza A (H1N1) and community-acquired methicillin-resistant Staphylococcus aureus clone USA300: successful management of the first documented paediatric case.

Necrotising pneumonia in young, previously healthy patients due to Panton–Valentine leucocidin (PVL) producing Staphylococcus aureus has been increasingly recognised. PVL pneumonia is often associated with influenza co-infection and high mortality. This case report describes the successful management of the first documented paediatric case of a previous healthy adolescent who developed necrotising pneumonia due to community-acquired methicillin-resistant (CA-MRSA) clone USA300 with pandemic influenza A (H1N1) co-infection, and highlights the importance of early recognition and initiation of appropriate therapy for this potentially fatal co-infection. PCR remains the gold standard to diagnose pandemic H1N1 since it may not be detected by rapid antigen tests. Bacterial necrotising pneumonia should be suspected in those presenting with worsening flu-like symptoms and clinical and/or radiological evidence of PVL infection (multifocal infiltrates, effusion and cavitation). These patients may benefit from the administration of toxin neutralising agents. In light of the current H1N1 pandemic, healthcare professionals will be increasingly confronted with this clinical scenario.

Asma en la edad pediátrica : proceso asistencial integrado

Este documento (2003), junto con el de Asma en la edad adulta (2004), han sido unificados en un único Proceso Asistencial Integrado: Asma (2012)[http://hdl.handle.net/10668/674]. Publicado en la página web de la Consejería de Salud y Bienestar Social: www.juntadeandalucia.es/salud (Consejería de Salud y Bienestar Social/ Profesionales / Nuestro Compromiso por la Calidad / Proceso Asistencial Integrado Asma / Histórico de documentos del PAI Asma)

Asma del adulto : proceso asistencial integrado

Este documento (2004), junto con el de Asma en la edad pediátrica (2003), han sido unificados en un único Proceso Asistencial Integrado: Asma (2012)[http://hdl.handle.net/10668/674]. Publicado en la página web de la Consejería de Salud y Bienestar Social: www.juntadeandalucia.es/salud (Consejería de Salud y Bienestar Social/ Profesionales / Nuestro Compromiso por la Calidad / Proceso Asistencial Integrado Asma / Histórico de documentos del PAI Asma)

Asma : proceso asistencial integrado

Este Proceso (2012) integra los dos publicados anteriormente de Asma en la edad pediátrica (2003) y Asma en la edad adulta (2004). Fichero en formato pdf, publicado en la página web de la Consejería de Salud y Bienestar Social: www.juntadeandalucia.es/salud (Consejería de Salud y Bienestar Social / Profesionales / Nuestro Compromiso por la Calidad / Procesos Asistenciales Integrados)

High Prevalence of Systemic Autoimmune Diseases in Patients with Meniere's Disease

BACKGROUND. Autoimmunity appears to be associated with the pathophysiology of Meniere's disease (MD), an inner ear disorder characterized by episodes of vertigo associated with hearing loss and tinnitus. However, the prevalence of autoimmune diseases (AD) in patients with MD has not been studied in individuals with uni or bilateral sensorineural hearing loss (SNHL). METHODS AND FINDINGS. We estimated the prevalence of AD in 690 outpatients with MD with uni or bilateral SNHL from otoneurology clinics at six tertiary referral hospitals by using clinica criteria and an immune panel (lymphocyte populations, antinuclear antibodies, C3, C4 and proinflammatory cytokines TNFα, INFγ). The observed prevalence of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and ankylosing spondylitis (AS) was higher than expected for the general population (1.39 for RA, 0.87 for SLE and 0.70 for AS, respectively). Systemic AD were more frequently observed in patients with MD and diagnostic criteria for migraine than cases with MD and tension-type headache (p = 0.007). There were clinical differences between patients with uni or bilateral SNHL, but no differences were found in the immune profile. Multiple linear regression showed that changes in lymphocytes subpopulations were associated with hearing loss and persistence of vertigo, suggesting a role for the immune response in MD. CONCLUSIONS. Despite some limitations, MD displays an elevated prevalence of systemic AD such as RA, SLE and AS. This finding, which suggests an autoimmune background in a subset of patients with MD, has important implications for the treatment of MD.