Reliability of blood eosinophil count in steady-state bronchiectasis.

RATIONALE: The baseline value of eosinophils in peripheral blood (BEC) has been associated with different degrees of severity, prognosis and response to treatment in patients with bronchiectasis. It is not known, however, if this basal value remains constant over time. OBJECTIVES: The aim of this study was to assess whether the BEC remains stable in the long term in patients with bronchiectasis. METHODS AND MEASUREMENTS: Patients from the RIBRON registry of bronchiectasis diagnosed by computed tomography with at least 2 BEC measurements one year apart were included in the study. Patients with asthma and those taking anti-eosinophilic drugs were excluded. Reliability was assessed using the intra-class correlation coefficient (ICC). A patient with a BEC of at least 300 cells/uL or less than 100 cells/uL was considered eosinophilic or eosinopenic, respectively. Group changes over time were also calculated. MAIN RESULTS: Seven hundred and thirteen patients were finally included, with a mean age of 66.5 (13.2) years (65.8 % women). A total of 2701 BEC measurements were performed, with a median number of measurements per patient of 4 (IQR: 2-5) separated by a median of 12.1 (IQR: 10.5-14.3) months between two consecutive measurements. The ICC was good (>0.75) when calculated between two consecutive measurements (approximately one year apart) but had dropped significantly by the time of the next annual measurements. Similarly, the change from an eosinophilic or eosinopenic patient to a non-eosinophilic or non-eosinopenic patient, respectively, was less than 30 % during the first year with respect to the baseline value but was close to 50 % in later measurements. CONCLUSIONS: Given the significant changes observed in the baseline value of the BEC over time, its monitoring is necessary in patients with bronchiectasis in order to more reliably assess its usefulness.

Pseudomonas aeruginosa and lung function decline in patients with bronchiectasis.

OBJECTIVES: The objective of this study was to analyse lung function decline over time in bronchiectasis, along with the factors associated with it. METHODS: Spirometry was measured every year in this observational, prospective study in 849 patients from the Spanish Bronchiectasis Registry (RIBRON). The main outcome was the decline in the rate of forced expiratory volume during the first second (FEV1). To be included in this study, patients needed a baseline assessment and at least one subsequent assessment. FEV1 decline was analysed using a mixed-effects linear regression model adjusted for clinically significant variables. RESULTS: We recruited 849 bronchiectasis patients with at least two annual lung function measurements (follow-up range 1-4 years). A total of 2262 lung function tests were performed (mean 2.66 per patient, range 2-5). Mean baseline FEV1 was 1.78 L (standard deviation (SD) 0.76; 71.3% predicted). Mean age was 69.1 (SD 15.4) years; 543 (64% women. The adjusted rates of FEV1 decline were -0.98% predicted/year (95% confidence interval (CI) -2.41 to -0.69) and -31.6 (95% CI -44.4 to -18.8) mL. The annual FEV1 decline was faster in those patients with chronic bronchial infection by Pseudomonas aeruginosa (-1.37% (52.1 mL) vs -0.37% (-24.6 mL); p < 0.001), greater age, increased number of severe exacerbations in the previous year and higher baseline FEV1 value. DISCUSSION: In patients with bronchiectasis, the annual rate of FEV1 decline was -31.6 mL/year and it was faster in older patients and those with chronic bronchial infection by P. aeruginosa, increased number of previous severe exacerbations and higher baseline FEV1 value.

Aerosolized Lipid Amphotericin B for Complementary Therapy and/or Secondary Prophylaxis in Patients with Invasive Pulmonary Aspergillosis: A Single-Center Experience.

BACKGROUND: Experience with aerosolized lipid amphotericin B (aeLAB) as therapy or secondary prophylaxis in patients with invasive pulmonary aspergillosis (IPA) is anecdotal. METHODS: We performed a single-center retrospective cohort study to evaluate the efficacy of systemic antifungal therapy with and without aeLAB in patients with proven or probable IPA. Complete or partial response at 3 months was the primary end-point. Clinical response and mortality at 12 months, occurrence of adverse drug reactions and respiratory fungal colonization were secondary end-point. RESULTS: Eleven patients (39%) received aeLAB in addition to systemic antifungal therapy (group A), and 22 (61%) received systemic antifungal therapy only (group B). The use of aeLAB was not standardized. Amphotericin B lipid complex was used in all patients but one, who received liposomal amphotericin B. Five patients received aeLAB as antifungal complementary therapy and 6 received it as secondary prophylaxis. Except for the requirement of inhaled corticosteroids and home oxygen therapy, more frequent in group A, both groups were similar in baseline conditions. A better (nonsignificant) clinical outcome was observed at 3 months in patients receiving aeLAB. Only uncontrolled baseline condition was associated with one-year mortality in univariate analysis (p = 0.002). A multivariate Cox regression analysis suggests that aeLAB, corrected for uncontrolled underlying disease, reduces mortality at 12 months (HR 0.258; 95% CI 0.072-0.922; p = 0.037). CONCLUSION: Although no significant difference was observed in the main variable (3-month clinical response) and in spite of methodological limitations of the study, the possible survival benefit of aeLAB, adjusted for the control of the underlying disease, could justify the performance of well-controlled studies with a greater number of patients.

Prevalence and factors associated with nontuberculous mycobacteria in non-cystic fibrosis bronchiectasis: a multicenter observational study.

BACKGROUND: Data on the prevalence of and factors associated with nontuberculous mycobacteria (NTM) in patients with non-cystic fibrosis (CF) bronchiectasis are limited. Our aim was to determine the prevalence and factors associated with isolation of NTM in this population. METHODS: We performed a multicenter observational study of historical cohorts comprising consecutive patients with non-CF bronchiectasis and at least 2 sputum samples cultured for mycobacteria over a period of 5 years. RESULTS: The study population included 218 adult patients (61.9 % women) with a mean (SD) age of 55.7 (16) years and a mean (SD) of 5.1 (3.3) cultures/patient. NTM was isolated from sputum in 18 patients (8.3 %). Of these, 5 patients (28 %) met the American Thoracic Society criteria for NTM disease. Mycobacterium avium complex was the most frequently isolated microorganism (9 patients, 4.1 %). The variables independently associated with isolation of NTM were FVC ≥ 75 % predicted (OR, 4.84; 95 % CI 1.47 to 15.9; p < 0.05), age ≥ 50 years (OR, 4.74; 95 % CI 1.25 to 17.97; p < 0.05), and body mass index (BMI) ≤ 23 kg/m(2) (OR, 2.97; 95 % CI 1.03-8.58; p < 0.05). Patients with these three characteristics had a 40 % probability of having at least one isolation of NMT. CONCLUSIONS: A significant number of patients with non-CF bronchiectasis are positive for the isolation of NTM. M. avium complex is the most frequently isolated mycobacteria. FVC ≥ 75 % predicted, age ≥ 50 years, and a BMI ≤ 23 kg/m(2) were independently associated with the presence of NTM in patients with non-CF bronchiectasis.

In vivo attenuation and genetic evolution of a ST247-SCCmecI MRSA clone after 13 years of pathogenic bronchopulmonary colonization in a patient with cystic fibrosis: implications of the innate immune response.

Methicillin-resistant Staphylococcus aureus (MRSA) causes chronic pulmonary infections in patients with cystic fibrosis (CF). This study tracks the 13-year evolution (1996-2009) of a single MRSA clone in a male patient with CF, evaluating both the host immunogenic response and the microbial variations. Whole-genome sequencing was performed for the initial (CF-96) and evolved (CF-09) isolates. The immunogenicity of CF-96 and CF-09 was evaluated by incubation with innate immune cells from healthy volunteers. We also studied the patient's innate immune response profile, cytokine production, expression of triggering receptor expressed on myeloid cells-1 (TREM-1), and phagocytosis. A total of 30 MRSA ST247-SCCmecI-pvl(-) isolates were collected, which evidenced a genome size reduction from the CF-96 ancestor to the evolved CF-09 strain. Up to six changes in the spa-type were observed over the course of the 13-year evolution. Cytokine production, TREM-1 expression, and phagocytosis were significantly lower for the healthy volunteer monocytes exposed to CF-09, compared with those exposed to CF-96. Patient monocytes exhibited a reduced inflammatory response when challenged with CF-09. Genetic changes in MRSA, leading to reduced immunogenicity and entry into the refractory state, may contribute to the attenuation of virulence and efficient persistence of the bacteria in the CF lung.

Fibrosis quística diagnosticada en edad adulta / Cystic fibrosis in adult age

Objetivo. Precisar la prevalencia de enfermos con fibrosis quística (FQ) diagnosticados en edades superiores a los 18 años y analizar sus características clínicas, genéticas y microbiológicas. Pacientes y métodos. Estudio observacional, transversal y descriptivo de todos los pacientes diagnosticados de FQ a edad igual o superior a los 18 años. Las variables analizadas fueron: edad actual, edad al diagnóstico, sexo, nacionalidad, parámetros de función pulmonar, patologías presentes al momento del diagnóstico, características microbiológicas y hallazgos genéticos. Resultados. Se incluyeron 89 pacientes (14,8%, del total de 600 pacientes en seguimiento en las unidades participantes), 45 mujeres (50,6%) y 44 varones (49,4%), con una edad media al diagnóstico de 36,4 años. Ochenta y un pacientes (91%) eran de nacionalidad española. La prueba del sudor fue diagnóstica en 77 de los 89 estudiados (86,5%). Las mutaciones detectadas con mayor frecuencia fueron la F508del/otra y la G542X/otra y los hallazgos clínicos más frecuentes en el momento del diagnóstico fueron las bronquiectasias en 33 pacientes (37,1%) y la esterilidad en 12 (13,5%). Los microorganismos colonizadores más frecuentes fueron Staphylococcus aureus (S.aureus) sensible a meticilina (23,6%) y Pseudomonas aeruginosa (P. aeruginosa) (13,5%). La mayoría de los pacientes presentaban una alteración ventilatoria obstructiva leve y no tenía afectación pancreática. La prueba del sudor con frecuencia ofreció resultados no concluyentes. Conclusiones. La FQ es también una enfermedad de diagnóstico en la edad adulta. Los pacientes diagnosticados en edad adulta presentan una función pulmonar levemente alterada y una baja incidencia de afectación pancreática, por lo que su pronóstico tiende a ser favorable (AU)

Aim. To know the prevalence of the patients diagnosed of cystic fibrosis (CF) older than 18 years old of five specific Spanish Units and to analyze their clinical, genetic and microbiological characteristics. Patients and methods. Observational, cross-sectional, descriptive study of patients diagnosed with CF at age or older than 18 years. The variables analyzed were: current age, age at diagnosis, sex, nationality, lung function parameters, pathologies presented at diagnosis, microbiological features and genetic findings. Results. Eigthy nine patients (14.8% of the total of 600 CF patients followed at the participating units), of which 45 patients were female (50.6%) and 44 were males (49.4%), were included with a mean age at diagnosis of 36.4 years. Eigthy one patients (91%) were Spaniards. The sweat test was diagnostic in 77 (86.5%) of the patients studied. The sweat test was diagnostic in 77 of the 89 patients studied (86.5%). The most frequently detected mutations were F508del/other and G542X/other, and the most frequent clinical findings at diagnosis were the presence of bronchiectasis in 33 patients (37.1%) followed by sterility in 12 patients (13.5%). The most common colonizing organisms were meticillin-sensitive Staphylococcus aureus (S.aureus) (23.6%) and Pseudomonas aeruginosa (P. aeruginosa) (13.5%). Most patients presented a mild obstructive ventilatory defect and had no pancreatic involvement. The sweat test used to be indeterminate. Conclusions. CF is also a disease which diagnosis can be in adulthood. CF patients diagnosed in adulthood have a mild lung function and lower incidence of pancreatic involvement, so their prognosis tends to be favorable (AU)

Cystic fibrosis in adult age. / Fibrosis quística diagnosticada en edad adulta.

AIM: To know the prevalence of the patients diagnosed of cystic fibrosis (CF) older than 18 years old of five specific Spanish Units and to analyze their clinical, genetic and microbiological characteristics. PATIENTS AND METHODS: Observational, cross-sectional, descriptive study of patients diagnosed with CF at age or older than 18 years. The variables analyzed were: current age, age at diagnosis, sex, nationality, lung function parameters, pathologies presented at diagnosis, microbiological features and genetic findings. RESULTS: Eigthy nine patients (14.8% of the total of 600 CF patients followed at the participating units), of which 45 patients were female (50.6%) and 44 were males (49.4%), were included with a mean age at diagnosis of 36.4 years. Eigthy one patients (91%) were Spaniards. The sweat test was diagnostic in 77 (86.5%) of the patients studied. The sweat test was diagnostic in 77 of the 89 patients studied (86.5%). The most frequently detected mutations were F508del/other and G542X/other, and the most frequent clinical findings at diagnosis were the presence of bronchiectasis in 33 patients (37.1%) followed by sterility in 12 patients (13.5%). The most common colonizing organisms were meticillin-sensitive Staphylococcus aureus (S.aureus) (23.6%) and Pseudomonas aeruginosa (P. aeruginosa) (13.5%). Most patients presented a mild obstructive ventilatory defect and had no pancreatic involvement. The sweat test used to be indeterminate. CONCLUSIONS: CF is also a disease which diagnosis can be in adulthood. CF patients diagnosed in adulthood have a mild lung function and lower incidence of pancreatic involvement, so their prognosis tends to be favorable.

Tos en el niño / Cough in the child

La tos en la infancia es un síntoma muy frecuente, siendo uno de los motivos de consulta más comunes en la práctica pediátrica diaria. En la mayoría de casos se debe a infecciones respiratorias banales. Raramente se asocia a problemas graves, pero todo niño con tos persistente durante más de 8 semanas debe ser evaluado, para descartar patologías tales como el asma y la bronquitis bacteriana persistente, entre otras. En cada caso es preciso, si es posible, realizar un tratamiento específico basado en la etiología, por lo que tendremos que hacer todo lo posible para encontrar la causa subyacente. Con un abordaje adecuado podremos llegar a identificar su etiología en el 80% de los casos. Si es así el tratamiento será efectivo en el 90% de ellos. No hay evidencia científica que justifique el empleo de tratamientos sintomáticos que alivien la tos, tales como jarabes antitusígenos; incluso algunos datos sugieren potenciales efectos dañinos. En algunos casos deberemos realizar un tratamiento empírico en base a las características y especificad ilusa de la tos (AU)

The cough in childhood is a very frequent symptom, this being one of the most common reasons for the medical visit in the daily pediatric practice. In most of the cases, it is due to common respiratory infections. It is rarely associated to serious problems, however, any child having a cough persisting for more than 8 weeks should be studied to rule out conditions such as asthma, persistent bacterial bronchitis, among others. It is necessary in every case, if possible, to carry out a specific treatment based on the etiology. Thus, we must do everything possible to find the underlying cause. With an adequate approach, we can identify its etiology is 80% of the cases. If this occurs, treatment will be effective in 90% of them. There is no scientific evidence that justifies the use of symptomatic treatment to relieve the cough , such as cough suppressants. Some data even suggest potential harmful effects. In some cases, it is necessary to perform an empirical treatment based on the characteristics and specificity of the cough (AU)

Actualización en el tratamiento de la enfermedad pulmonar en fibrosis quística / Update in the treatment of lung disease in cystic fibrosis

La fibrosis quística (FQ) es una enfermedad autosómica recesiva que afecta, aproximadamente, a 1 de cada 4.500 recién nacidos vivos en las personas de raza caucásica. Está causada por mutaciones de un solo gen, localizado en el brazo largo del cromosoma 7, que codifica una proteína de 1.480 aminoácidos llamada proteína reguladora de la conducción de iones en las membranas (CFTR). Esta proteína se comporta como un canal de cloro e indirectamente controla los movimientos del sodio, bicarbonato y agua a través de las membranas celulares. Hasta el momento actual, se han identificado alrededor de 1.800 mutaciones en esta enfermedad. El descubrimiento del gen de FQ, el aislamiento de la proteína CFTR y el mejor en rendimiento de los mecanismos moleculares que determinan las manifestaciones clínicas de la FQ han sido trasladados a nuevos tratamientos. Los tratamientos para la FQ y sus manifestaciones clínicas, que son discutidos en este artículo, incluyen antibióticos inhalados, terapias de hidratación, agentes anti-inflamatorios y modificadores de proteínas. También se discuten nueves tratamientos en experimentación y desarrollo. Los objetivos de estas terapias son la mejoría del flujo espiratorio forzado en el primer segundo (FEV1), la mejoría de la calidad de vida y la disminución del uso de antibióticos y del número de exacerbaciones pulmonares (AU)

Cystic fibrosis (CF) is an autosomal recessive disorder that affects, approximately, 1 in 4,500 Caucasian births. Is caused by mutations in one gene localized in large arm of 7 chromosome which encoded a 1,480 aminoacid protein called cystic fibrosis transmembrane conductance regulator (CFTR). This protein is a channel of chloride and indirectly controlled the transport of sodium, bicarbonate and water between the cellular membranes. The discovery of the CF gene, isolation of the CFTR protein and the better understanding of molecular mechanisms behind the clinical expression of CF are being translated into new treatments. Treatments for CF and its manifestations are discussed in this article including inhaled antibiotics. Hydrator therapies, anti-inflammatory agents and protein modifiers. New and experimental treatments that are development are also discussed. Outcomes for these treatments are Forced Expiratory Volume in one second (FEV1), improvement CF-related quality of life, use of intravenous antibiotics and frequency of exacerbations and hospitalizations (AU)

Clinical and microbiological features of a cystic fibrosis patient chronically colonized with Pandoraea sputorum identified by combining 16S rRNA sequencing and matrix-assisted laser desorption ionization-time of flight mass spectrometry.

Clonal isolates identified as various nonfermentative Gram-negative bacilli over a 5-year period from sputum cultures of a 30-year-old cystic fibrosis patient were successfully reidentified as Pandoraea sputorum by combining 16S rRNA sequencing and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). Decreased lung function improved after 1 year of azithromycin and inhaled 7%-hypertonic saline treatment.

Urgent lung transplantation in Spain.

BACKGROUND: Lung donors are scarce and lung transplantation resources are limited. Because urgent lung transplantation (ULT) is assumed to yield poor results, its use is controversial. We assessed the outcome of patients who received ULT seeking to determine effectiveness and risk factors. PATIENTS AND METHOD: We collected data from every ULT performed in Spain during 5 years (1998-2002). The survival of patients was studied using Kaplan-Meier, Cox regression, and chi-square statistical analyses. We compared outcomes and perioperative mortality (over 30 days) for ULT procedures, analyzing the influence of certain variables (age, type of transplant, diagnosis, indication, and time on waiting list). RESULTS: Among 109 patients proposed for the procedure, 73 ULT were performed during the period. The most frequent indications were pulmonary fibrosis (19 cases) and cystic fibrosis (19 cases), showing the worst and the better survival rates, respectively. The bad prognosis, determined mainly by per operative mortality rate (35.62%), was significantly affected by age (worse for patients older than 40 years) and type of LT (single worse than double; P < .05). A longer time waiting for ULT also showed a worse prognosis (P < .005). CONCLUSIONS: Long-term survival after ULT shows that the procedure is effective and efficient for a select group of patients, despite the high per operative risk. ULT should be reserved for younger patients. It also requires performance in a short period (just a few days), initially rejecting a single lung transplant, provided that the patient is adequately monitored.

Conferencia de consenso. Tratamiento antibiótico intravenoso domiciliario en la fibrosis quística / Consensus conference: home intravenous antibiotic treatment for cystic fibrosis

No disponible

[Asthmatic characteristics in smokers with advanced emphysema]. / Características asmáticas en pacientes fumadores con enfisema avanzado.

OBJECTIVES: Most pneumologists assume that chronic asthma and emphysema associated with smoking differ both in their etiology and type of inflammation. However, it is difficult to study subjects who have both diseases simultaneously. We designed a prospective study to determine whether or not some advanced emphysema patients who are smokers have an asthmatic profile suggesting the two diseases overlap. PATIENTS AND METHOD: Twenty-three smokers with moderate to severe obstruction and radiologic signs of advanced emphysema were studied. The following signs of asthma were analyzed for all patients: positive acute response to bronchodilators, eosinophilia in peripheral blood, significant eosinophilia in sputum, significant total serum immunoglobulin E (IgE) and specific IgE positive for common allergens and fungi. An asthmatic profile was defined as the presence of 3 or more of the aforementioned signs. Statistical analysis was by calculation of the confidence interval on the total number of positive cases to estimate the population percentage. RESULTS: Data on at least 4 characteristics were available for 21 of the 23 patients. Ten (48%) of the 21 had asthmatic profiles (3 or more of the aforementioned characteristics). This finding suggests that asthmatic characteristics are present in between 17.6 and 79.6% of the studied population with advanced emphysema, with a confidence interval of 99.9%. CONCLUSIONS: We conclude that emphysema initially associated with smoking may mean that at least 17.6% of patients have a clear asthmatic profile, which indicates a high degree of overlap between asthma and emphysema in smokers. Thus, our findings are consistent with the Dutch theory that chronic obstructive diseases have a common origin in underlying allergic sensitization and bronchial hyperresponsiveness alongside various other influential factors such as tobacco smoking over the course of disease.

Características asmáticas en pacientes fumadorescon enfisema avanzado / Asthmatic characteristics in smokers with advanced emphysema

OBJETIVOS: La mayoría de los neumólogos asumen que el asma crónica y el enfisema asociado al fumar difieren tanto en su origen como en el tipo de inflamación, pero es difícil que se estudie a individuos que presenten simultáneamente ambos procesos. Nosotros pretendemos averiguar mediante un análisis prospectivo si una porción de pacientes fumadores con enfisema avanzado tienen un perfil asmático, lo que supondría un solapamiento de ambas entidades. PACIENTES Y MÉTODO: Se estudió a una población de 23 fumadores afectados de obstrucción moderada a grave al flujo aéreo y con criterios radiológicos de enfisema avanzado. Se analizó en todos los pacientes el perfil asmático definido mediante 5 características: respuesta aguda positiva a broncodilatadores, eosinofilia en sangre periférica, eosinófilos en esputo significativos, IgE sérica total significativa e IgE específica positiva a alergenos comunes y hongos. Se consideró presente el perfil asmático si se daban en un paciente tres o más de las características citadas. El análisis estadístico se hizo construyendo intervalos de confianza sobre los casos positivos totales para estimar la proporción poblacional. RESULTADOS: De los 23 pacientes, en 21 se pudo analizar al menos 4 de las características. De los 21 pacientes, 10 (48 por ciento) presentaban un perfil asmático, es decir, tenían tres o más de las características antes señaladas. Este dato supone una proporción positiva de la presencia de características asmáticas de entre el 17,6 y el 79,6 por ciento de la población analizada con enfisema avanzado, con un intervalo de confianza del 99,9 por ciento de probabilidad. CONCLUSIONES: En el enfisema asociado en principio al hábito de fumar se podría admitir que al menos un 17,6 por ciento de los pacientes presentan un perfil asmático evidente, lo que supone un alto grado de solapamiento entre asma y enfisema del fumador, y por eso no se desmiente la teoría holandesa sobre el origen común de las enfermedades obstructivas crónicas que sostiene una base inicial de sensibilización alérgica e hiperreactividad bronquial e influencias diversas, como el humo de tabaco, en la evolución final a largo plazo (AU)

Patógenos multirresistentes en la fibrosis quística / Multiresistant pathogens in cystic fibrosis

No disponible