José Serrano

FREQUENCY AND CLINICAL CHARACTERISTICS OF RAPID-ONSET FATAL AND NEAR-FATAL ASTHMA

The onset of fatal and near-fatal asthma attacks can be rapid. The objective of this study was to determine the frequency and clinical characteristics of rapid-onset asthma (ROA) in patients suffering fatal and near-fatal crises. Two-hundred and twenty patients with fatal or near-fatal attacks were enrolled in a multicentre, prospective study. ROA was defined as a crisis developing in ≤2 h. Data on patient and clinical characteristics were collected, and spirometric and allergy studies were performed when the patients were in a stable condition. Forty-five attacks (20%) were ROA and 175 (80%) were slow-onset asthma (SOA). The triggers for SOA and ROA attacks were different, with the ROA group having a significantly lower rate of suspected respiratory infection (7% versus 38%), higher rates of fume/irritant inhalation (9% versus 1%) and a higher intake of nonsteroidal anti-inflammatory drugs (14% versus 3%). The ROA group exhibited significantly higher rates of impaired consciousness (63% versus 44%), absence of lung sounds upon admission (68% versus 42%), fewer hours of mechanical ventilation (13 h versus 28 h) and fewer days of hospitalization (8 days versus 9.5 days) than the SOA group. The 20% frequency of rapid-onset fatal and near-fatal attacks in this study suggests that rapidly developing attacks may not be rare. These findings also support a distinct clinical profile for rapid-onset asthma marked by differences in triggers, severity of exacerbation and clinical course.

Genome-Wide Association Study of Survival in Non–Small Cell Lung Cancer Patients Receiving Platinum-Based Chemotherapy

BACKGROUND Interindividual variation in genetic background may influence the response to chemotherapy and overall survival for patients with advanced-stage non-small cell lung cancer (NSCLC). METHODS To identify genetic variants associated with poor overall survival in these patients, we conducted a genome-wide scan of 307,260 single-nucleotide polymorphisms (SNPs) in 327 advanced-stage NSCLC patients who received platinum-based chemotherapy with or without radiation at the University of Texas MD Anderson Cancer Center (the discovery population). A fast-track replication was performed for 315 patients from the Mayo Clinic followed by a second validation at the University of Pittsburgh in 420 patients enrolled in the Spanish Lung Cancer Group PLATAX clinical trial. A pooled analysis combining the Mayo Clinic and PLATAX populations or all three populations was also used to validate the results. We assessed the association of each SNP with overall survival by multivariable Cox proportional hazard regression analysis. All statistical tests were two-sided. RESULTS SNP rs1878022 in the chemokine-like receptor 1 (CMKLR1) was statistically significantly associated with poor overall survival in the MD Anderson discovery population (hazard ratio [HR] of death = 1.59, 95% confidence interval [CI] = 1.32 to 1.92, P = 1.42 × 10(-6)), in the PLATAX clinical trial (HR of death = 1.23, 95% CI = 1.00 to 1.51, P = .05), in the pooled Mayo Clinic and PLATAX validation (HR of death = 1.22, 95% CI = 1.06 to 1.40, P = .005), and in pooled analysis of all three populations (HR of death = 1.33, 95% CI = 1.19 to 1.48, P = 5.13 × 10(-7)). Carrying a variant genotype of rs10937823 was associated with decreased overall survival (HR of death = 1.82, 95% CI = 1.42 to 2.33, P = 1.73 × 10(-6)) in the pooled MD Anderson and Mayo Clinic populations but not in the PLATAX trial patient population (HR of death = 0.96, 95% CI = 0.69 to 1.35). CONCLUSION These results have the potential to contribute to the future development of personalized chemotherapy treatments for individual NSCLC patients.

Alexithymia: a relevant psychological variable in near-fatal asthma

Alexithymia is a psychological trait characterised by difficulty in perceiving and expressing emotions and body sensations. Failure to perceive dyspnoea could lead alexithymic asthmatics to underestimate the severity of an asthma exacerbation, and thereby increase the risk of developing a fatal or near-fatal asthma (NFA) attack. The objective of the present study was to determine the prevalence of alexithymia in NFA patients and to analyse their clinical characteristics. Alexithymia was assessed using the Toronto Alexithymia Scale in this multicentric prospective observational study. From 33 Spanish hospitals, 179 NFA patients and 40 non-NFA patients, as a control group, were enrolled. There was a higher proportion of alexithymia in the NFA group than in the non-NFA group (36 versus 13%). Patients with NFA and alexithymia were older than the rest of the NFA group, and had a lower level of education, a higher level of psychiatric morbidity, a higher proportion of severe persistent asthma and a greater number of prior very severe asthma exacerbations (49 versus 27%). Alexithymia, severe persistent asthma and a low level of education were identified as independent variables related to repeated very severe asthma exacerbations. The results show that alexithymia is more frequent in near-fatal asthma patients compared to the rest of asthmatics and is associated with recurrent very severe asthma exacerbations.

Circulating Immunoreactive Somatostatin in Gastrointestinal Diseases: Decrease after Vagotomy and Enhancement in Active Ulcerative Colitis, Irritable Bowel Syndrome, and Duodenal Ulcer

The main source of circulating immunoreactive somatostatin (IRS) seems to be the gastrointestinal tract. We therefore investigated plasma IRS in patients with various gastrointestinal diseases. Mean basal IRS oscillated between 46 and 73 pg/ml. A postprandial rise was observed in all patients and age-matched controls. However, the increment was significantly higher in patients with duodenal ulcer (159 +/- 20 pg/ml), active ulcerative colitis (176 +/- 17 pg/ml), and irritable bowel syndrome (194.4 +/- 20.4 pg/ml). Patients with duodenal ulcers who underwent vagotomy showed a decreased postprandial increment (107 +/- 10 pg/ml) when compared with active duodenal ulcer patients. No difference was demonstrable between controls and individuals with gastric ulcer, and patients with inactive ulcerative colitis. These results suggest that vagal innervation plays a role in postprandial IRS stimulation, whereas gastric hyperacidity, acute lesions of the colonic mucosa, and hypermotility of the gastrointestinal tract are associated with an exaggerated postprandial IRS response. Since somatostatin is known to influence many gastrointestinal functions, these variations in circulating IRS concentrations may be of pathophysiologic importance.

Características clínicas de las crisis de asma de riesgo vital en los pacientes sensibilizados a Alternaria alternata

Fundamento y objetivo Algunas observaciones otorgan un papel relevante al hongo Alternaria alternata como desencadenante de crisis de asma de riesgo vital (ARV). El objetivo de este trabajo fue determinar si las crisis de ARV de los pacientes sensibilizados a Alternaria cursan con un perfil clinico diferencial. Pacientes y metodo Estudio descriptivo y multicentrico (33 hospitales espanoles) de 194 pacientes incluidos de forma prospectiva por padecer una crisis de ARV. Se recogieron las caracteristicas y el curso clinico de la crisis, y cuando alcanzaron la estabilidad clinica se les practicaron una espirometria, pruebas cutaneas de alergia y determinacion de IgE a Alternaria. Se establecio la sensibilizacion a Alternaria cuando la prueba cutanea o bien la IgE especifica resultaron positivas. Resultados En 20 de los pacientes (10%) se pudo constatar sensibilizacion a Alternaria. En comparacion con el grupo de pacientes no sensibilizados, los sensibilizados a Alternaria resultaron ser significativamente mas jovenes, con una media (DE) de edad de 35 (15) frente a 50 (21) anos (p Conclusiones Las caracteristicas clinicas constatadas en las crisis de ARV de los pacientes sensibilizados a Alternaria parecen distinguirlos como fenotipo particular. Una conducta de evitacion especifica podria comportar efectos beneficiosos al prevenir crisis de ARV en los pacientes sensibilizados.

Control of Ventilation, Breathlessness Perception and Alexithymia in Near-Fatal Asthma

Several studies have demonstrated impaired control of ventilation in some patients with near-fatal asthma (NFA). The objective of our study was to determine a possible relationship between alexithymia (a cognitive processing disorder), control of ventilation, and breathlessness perception in patients who had an NFA attack. We analyzed data from 100 subjects: 50 with NFA, 25 asthmatics without NFA, and 25 non-asthmatic controls. Ventilatory responses to hypoxia and hypercapnia were measured by the rebreathing technique in terms of slope of ventilation and mouth occlusion pressure (P0.1). Breathlessness perception was assessed with the Borg scale and alexithymia with the Toronto Alexithymia Scale (TAS). No statistical differences were observed between groups in breathlessness perception and ventilatory responses. The mean (SD) TAS score of 63.6 (14.9) in the NFA group was significantly higher than the score of 56.4 (12.1) in the non-asthmatic group (p = 0.007). More subjects with alexithymia were identified in the NFA group (24%) than in the non-NFA group (12%) or the non-asthmatic control group (12%). Although the presence of alexithymia did not correlate with poor ventilatory responses or breathlessness perception, it was associated with a larger number of previous hospitalisations: 6.2 (8.1) in the NFA group and 2.8 (4.8) in the non-NFA group (p = 0.036). In conclusion, the prevalence of alexithymia is higher among NFA patients than among asthmatics who have not experienced NFA attacks. Neither altered breathlessness perception nor ventilatory response to hypoxia seems to play a role in NFA, although alexithymia may favor poor clinical control.

Ingreso en el hospital por asma. Análisis descriptivo y factores pronósticos tras el alta

Fundamento En Espana, los estudios observacionales sobre los asmaticos que ingresan por una agudizacion de su enfermedad son escasos. El objetivo del presente estudio fue determinar las caracteristicas clinicas de estos pacientes y analizar que factores influyen en su evolucion tras el alta. Metodos Se incluyeron prospectivamente los asmaticos que ingresaron en nuestro hospital durante 12 meses consecutivos. Tras el alta, se efectuaron dos controles telefonicos al primer y cuarto mes. Se recogieron las caracteristicas demograficas y clinicas de los pacientes, las exacerbaciones, los reingresos, el tratamiento y el control medico recibidos. Resultados Se incluyeron 65 pacientes (44 mujeres y 21 varones; media de edad 45 anos; DE: 19). La mayoria (54%) ingreso en otono y las causas mas frecuentes de exacerbacion fueron las infecciones del tracto respiratorio (68%). El 54% de los pacientes presentaba asma grave, el 32% moderada y el 14% leve antes del ingreso. Durante el seguimiento, el 51% de los mismos presento, al menos, una exacerbacion del asma, el 38% preciso asistencia en urgencias y el 19% reingreso. Dos pacientes (3%) fallecieron por asma. El analisis de regresion logistica multiple relaciono la aparicion de exacerbaciones tras el alta con la mayor gravedad del asma y la ausencia de betaadrenergicos de accion prolongada; los reingresos se relacionaron con la menor duracion del tratamiento con glucocorticoides orales al alta y un mayor numero de ingresos hospitalarios previos. Conclusiones a) Los ingresos por asma se producen mayoritariamente en otono, probablemente en relacion con las infecciones de vias respiratorias, y no son exclusivos del asma grave; b) tras el alta, la morbilidad y la mortalidad de la enfermedad, a corto plazo, son elevadas, y c) la propia gravedad de la enfermedad y un tratamiento insuficiente son factores relacionados con una mala evolucion clinica del asma tras la hospitalizacion.

Separation and o-phthaldehyde fluorometric determination of 5-hydroxy- and 5-methoxyindoleamines by thin-layer chromatography: Selected applications

Individual 5-hydroxyindoles and 5-methoxyindoles were simultaneously isolated and quantified, after o-phthaldehyde condensation in different concentrations of HCl, followed by separation on silica gel plates. The 5-hydroxyindoleamines and 5-methoxyindoleamines were differentiated by intense orange and blue fluorescences, respectively. Distinct Rf values with new phase composition and optimal HCl concentrations in the condensation reaction were established for each of the nine indoleamines tested. Minimal detectable doses ranged from 0.2 ng for 5-methoxytryptophol to 4 ng for 5-hydroxyindole acetic acid. The above methodology was applied in order to determine platelet serotonin. Preliminary results suggest that this method could be adapted to other selected biological samples.

Bronchiectasthma and asthmectasis

Respiratory disease can be considered as a species in constant evolution. Due to population growth and ageing only, and apart from the current 1.1 billion smokers, there have never been more respiratory patients ever in history than today [1]. With the latest World Health Organization (WHO) worldwide estimates of 400 million individuals with rhinitis, 334 million asthmatics, 328 million chronic obstructive pulmonary disease (COPD) patients and over 100 million with sleep apnoea, there is plenty of opportunity for the concurrence of two or more respiratory diseases in the same person. Not surprisingly, it is now commonplace in medical journals and conferences to explore for syndromes that combine two respiratory conditions, such as COPD and sleep apnoea, asthma and COPD, lung cancer and pulmonary fibrosis, emphysema and bronchiectasis, etc. A relatively new kid on the block is, perhaps, bronchiectasis and asthma. Both chronic conditions are diagnosed clinically, with or without the help of imaging and lung function, and their flares (or exacerbations) share similar symptoms. Asthma and bronchiectasis: association or overlap http://ow.ly/YHcJS

Grado de conocimiento de las propias sensibilizaciones alérgicas en pacientes asmáticos y su repercusión en el nivel de control del asma

BACKGROUND Asthma guidelines recommend the adoption of allergen avoidance measures (AAM). To do so, patients need to know their own allergies. However, this degree of knowledge has not yet been assessed. The aims of this study were to determine, in allergic asthma patients: i)the degree of knowledge of their own allergic sensitizations; ii)the percentage of those who knew all their allergies and, in addition, adopted AAM against all of them, and iii)the possible impact of this degree of knowledge on the level of asthma control. PATIENTS AND METHODS Descriptive, prospective and multicentre study, including 147patients from 9 Respiratory Medicine outpatient clinics. After confirming the previous allergic asthma diagnosis, a questionnaire was completed. It included asthma control and severity levels, results of previous allergy tests, and the description and number of allergic sensitizations known by the patients and AAM followed. RESULTS Only 72 (49%) patients knew all their allergic sensitizations and only 48 (33%) were also following AAM against all the allergens to which they were allergic. No relationship was established between the degree of knowledge of their own allergies and the level of asthma control (P=.544). CONCLUSIONS Overall knowledge about the allergic nature of their disease among asthmatic patients attending Spanish Respiratory Medicine Departments is inadequate. Furthermore, a higher degree of knowledge of their allergies does not seem to lead, by itself, to better asthma control. Both findings seem to question the effectiveness of current educational strategies in this field and consequently, they should be revised.