Prph2 knock-in mice recapitulate human central areolar choroidal dystrophy retinal degeneration and exhibit aberrant synaptic remodeling and microglial activation.

Central areolar choroidal dystrophy is an inherited disorder characterized by progressive choriocapillaris atrophy and retinal degeneration and is usually associated with mutations in the PRPH2 gene. We aimed to generate and characterize a mouse model with the p.Arg195Leu mutation previously described in patients. Heterozygous (Prph2WT/KI) and homozygous (Prph2KI/KI) mice were generated using the CRISPR/Cas9 system to introduce the p.Arg195Leu mutation. Retinal function was assessed by electroretinography and optomotor tests at 1, 3, 6, 9, 12, and 20 months of age. The structural integrity of the retinas was evaluated at the same ages using optical coherence tomography. Immunofluorescence and transmission electron microscopy images of the retina were also analyzed. Genetic sequencing confirmed that both Prph2WT/KI and Prph2KI/KI mice presented the p.Arg195Leu mutation. A progressive loss of retinal function was found in both mutant groups, with significantly reduced visual acuity from 3 months of age in Prph2KI/KI mice and from 6 months of age in Prph2WT/KI mice. Decreased amplitudes in the electroretinography responses were observed from 1 month of age in Prph2KI/KI mice and from 6 months of age in Prph2WT/KI mice. Morphological analysis of the retinas correlated with functional findings, showing a progressive decrease in retinal thickness of mutant mice, with earlier and more severe changes in the homozygous mutant mice. We corroborated the alteration of the outer segment structure, and we found changes in the synaptic connectivity in the outer plexiform layer as well as gliosis and signs of microglial activation. The new Prph2WT/KI and Prph2KI/KI murine models show a pattern of retinal degeneration similar to that described in human patients with central areolar choroidal dystrophy and appear to be good models to study the mechanisms involved in the onset and progression of the disease, as well as to test the efficacy of new therapeutic strategies.

Transgenic Overexpression of Myocilin Leads to Variable Ocular Anterior Segment and Retinal Alterations Associated with Extracellular Matrix Abnormalities in Adult Zebrafish.

Myocilin is an enigmatic glaucoma-associated glycoprotein whose biological role remains incompletely understood. To gain novel insight into its normal function, we used transposon-mediated transgenesis to generate the first zebrafish line stably overexpressing myocilin [Tg(actb1:myoc-2A-mCherry)]. qPCR showed an approximately four-fold increased myocilin expression in transgenic zebrafish embryos (144 hpf). Adult (13 months old) transgenic animals displayed variable and age-dependent ocular anterior segment alterations. Almost 60% of two-year-old male, but not female, transgenic zebrafish developed enlarged eyes with severe asymmetrical and variable abnormalities in the anterior segment, characterized by corneal limbus hypertrophy, and thickening of the cornea, iris, annular ligament and lens capsule. The most severe phenotype presented small or absent ocular anterior chamber and pupils, due to iris overgrowth along with dysplastic retinal growth and optic nerve hypertrophy. Immunohistochemistry revealed increased presence of myocilin in most altered ocular tissues of adult transgenic animals, as well as signs of retinal gliosis and expanded ganglion cells and nerve fibers. The preliminary results indicate that these cells contributed to retinal dysplasia. Visual impairment was demonstrated in all old male transgenic zebrafish. Transcriptomic analysis of the abnormal transgenic eyes identified disrupted expression of genes involved in lens, muscular and extracellular matrix activities, among other processes. In summary, the developed transgenic zebrafish provides a new tool to investigate this puzzling protein and provides evidence for the role of zebrafish myocilin in ocular anterior segment and retinal biology, through the influence of extracellular matrix organization and cellular proliferation.

Decrease in DHA and other fatty acids correlates with photoreceptor degeneration in retinitis pigmentosa.

Fatty acids, and especially docosahexaenoic acid (DHA), are essential for photoreceptor cell integrity and are involved in the phototransduction cascade. In this study, we analyzed the changes in the fatty acid profile in the retina of the rd10 mouse, model of retinitis pigmentosa, in order to identify potential risk factors for retinal degeneration and possible therapeutic approaches. Fatty acids from C57BL/6J and rd10 mouse retinas were extracted with Folch's method and analyzed by gas chromatography/mass spectrometry. Changes in retinal morphology were evaluated by immunohistochemistry. The rd10 mouse retina showed a decreased number of photoreceptor rows and alterations in photoreceptor morphology compared to C57BL/6J mice. The total amount of fatty acids dropped by 29.4% in the dystrophic retinas compared to C57BL/6J retinas. A positive correlation was found between the retinal content of specific fatty acids and the number of photoreceptor rows. We found that the amount of several short-chain and long-chain saturated fatty acids, as well as monounsaturated fatty acids, decreased in the retina of rd10 mice. Moreover, the content of the n-6 polyunsaturated fatty acid arachidonic acid and the n-3 polyunsaturated DHA decreased markedly in the dystrophic retina. The fall of DHA was more pronounced, hence the n-6/n-3 ratio was significantly increased in the diseased retina. The content of specific fatty acids in the retina decreased with photoreceptor degeneration in retinitis pigmentosa mice, with a remarkable reduction in DHA and other saturated and unsaturated fatty acids. These fatty acids could be essential for photoreceptor cell viability, and they should be evaluated for the design of therapeutical strategies and nutritional supplements.

Child Head Circumference and Placental MFSD2a Expression Are Associated to the Level of MFSD2a in Maternal Blood During Pregnancy.

Gestational diabetes mellitus (GDM) is a world-wide health challenge, which prevalence is expected to increase in parallel to the epidemic of obesity. Children born from GDM mothers have lower levels of docosahexaenoic acid (DHA) in cord blood, which might influence their neurodevelopment. Recently, the membrane transporter Major Family Super Domain 2a (MFSD2a) was associated with the selective transportation of DHA as lysophospholipids. The expression of the DHA membrane transporter MFSD2a is lower in GDM placentas, which could affect materno-fetal DHA transport. Humans with homozygous inactivating mutations in the MFSD2a gene present severe microcephaly and intellectual impairments. Herein, we intended to identify early blood biomarkers that may be of use during pregnancy to monitor the offspring development and the adequate nutritional interventions, such as nutritional supplementation, that may be selected to improve it. We evaluated MFSD2a expression in maternal blood at the third trimester of pregnancy, and its potential relationship with the expression of placental MFSD2a at delivery and child outcomes. Three groups of pregnant women were recruited: 25 controls, 23 GDM with dietary treatment, and 20 GDM with insulin treatment. Maternal and neonatal anthropometric and biochemical parameters were evaluated. MFSD2a was analyzed in placenta, blood and serum. MFSD2a protein expression in maternal blood was significantly lower in GDM groups and correlated with placental MFSD2a and Z-score neonatal head circumference during the first 6 months of life. The cord/maternal serum ratio of DHA, a solid indicator of materno-fetal DHA transport, was reduced in GDM groups and correlated with MFSD2a in maternal blood at the third trimester and in placenta at delivery. This indicates that altered MFSD2a levels in maternal blood during pregnancy might influence placental nutrient transport and fetal neurodevelopment. Furthermore, MFSD2a levels in maternal blood on the third trimester were inversely correlated to DHA in maternal serum lyso-PL. Thus, the level of MFSD2a in maternal blood could be used as a potential biomarker for the early detection of disturbances of MFSD2a expression during pregnancy and the subsequent consequences for the neurodevelopment of the child, as well as it may help to choose the optimal treatment approach for the affected subjects.

Decreased Blood Level of MFSD2a as a Potential Biomarker of Alzheimer's Disease.

The protein Major Facilitator Superfamily Domain containing 2A (MFSD2a) was recently described as the primary carrier for docosahexaenoic acid (DHA) into the brain. Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by lower DHA levels in blood lipids. The aim of this study was to investigate the expression of MFSD2a in the whole blood and brain as a potential biomarker of AD. Three groups were established: 38 healthy controls, 48 subjects with moderate AD (GDS4), and 47 with severe AD (GDS6). We analyzed postmortem brain samples from the hippocampus of 11 healthy controls and 11 severe AD patients. Fatty acid (FA) was determined in serum and brain by gas chromatography. Blood and brain MFSD2a protein expression was analyzed by Western blotting. We found a significant and progressive decline of MFSD2a levels in blood of AD patients (Control 0.83 ± 0.13, GDS4 0.72 ± 0.09, GDS6 0.48 ± 0.05*, p ˂ 0.01). We also corroborated a significant reduction of DHA and other n-3 long-chain polyunsaturated FA in serum of AD. No differences were found in MFSD2a expression or FA levels in brain of controls and AD subjects. MFSD2A carrier was analyzed in AD patients for the first time and the level of MFSD2a in the whole blood could be a potential biomarker of this disease.

Termometría timpánica en pediatría como alternativa al termómetro de mercurio / The tympanic thermometer in pediatrics as an alternative to the mercury-in-glass thermometer

Objetivos. Conocer el comportamiento de un nuevo modelo de termómetro de infrarrojos de cono más pequeño y valorar si es una alternativa adecuada para la determinación de la fiebre en niños menores de 14 años. Método. Estudio descriptivo transversal que compara las temperaturas tomadas con termómetro de mercurio y termómetro de infrarrojos en menores de 14 años. Las investigadoras siguieron las instrucciones de uso de cada termómetro. En una muestra de 400 niños se hicieron 2 grupos de edad: grupo I, menores de 2 años, y grupo II, desde los 2 hasta los 14 años. Para el grupo I se utilizó el termómetro de mercurio rectal durante 3 min en recto y el termómetro timpánico en modo rectal en oído derecho. Para el grupo II el termómetro de mercurio axilar durante 8 min en axila derecha y termómetro timpánico en modo axilar. Para analizar el sesgo intraobservador, se seleccionaron 50 pacientes de la muestra a los que 2 enfermeras del equipo tomaron las temperaturas de forma simultánea. Tanto para medir la fiabilidad del termómetro timpánico como para analizar el sesgo intraobservador se utilizó el coeficiente de correlación intraclase (CCI). Resultados. El acuerdo entre las mediciones de temperatura con ambos instrumentos se ha medido por el CCI. Para el grupo I se obtuvo un CCI=0,91 (intervalo de confianza [IC] del 95%, 0,88-0,94) y para el grupo II un CCI=0,90 (IC del 95%, 0,87-0,92). La reproducibilidad de las mediciones realizadas por 2 enfermeras en 50 pacientes ha mostrado para el termómetro timpánico un CCI=0,97 (IC del 95%, 0,95-0,98). Conclusiones. El termómetro de infrarrojos es un dispositivo adecuado de valoración rápida de temperatura en nuestra área de trabajo de urgencias. Pero se deben confirmar las temperaturas con otro método cuando implique decisiones clínicas(AU)

Objectives. To determine the behavior of a new and smaller model of infrared thermometer cone and to assess whether it is an appropriate alternative to determine fever in children under 14 years old. Method. We performed a cross-sectional, descriptive study comparing the temperatures taken with a mercury thermometer with those taken by an infrared thermometer in children under 14 years old. The researchers followed the manufacturer's instructions for use for each thermometer. The overall sample of 400 children was divided into two age groups. Group I consisted of children aged less than 2 years and group II of 2–14-years-old. In group I the rectal mercury thermometer was placed in the rectum for 3minutes and the tympanic thermometer was used in rectal mode and placed in the right ear. In group II, the axillary mercury thermometer was placed for 8 minutes in the right axilla and the tympanic thermometer was used in the axillary mode. To analyze intraobserver bias, 50 patients were selected from the sample and their temperatures were simultaneously taken by two nurses from the team. The intraclass correlation coefficient (ICC) was used both to measure the reliability of the tympanic thermometer and to analyze intraobserver bias. Results. Temperature measurements with both instruments showed an ICC of 0.91 (95% confidence interval [CI], 0.88–0.94) for group I and 0.90 (95%CI, 0.87-0.92) for group II. The reproducibility of the measurements taken by the two nurses in 50 patients showed an ICC of 0.97 (95% CI, 0.95-0.98) for the tympanic thermometer. Conclusions. The infrared thermometer is an appropriate device for rapidly measuring temperature in the emergency department. However, the measurements taken should be confirmed by another method when clinical decisions are based on temperature values(AU)

[The tympanic thermometer in pediatrics as an alternative to the mercury-in-glass thermometer]. / Termometría timpánica en pediatría como alternativa al termómetro de mercurio.

OBJECTIVES: To determine the behavior of a new and smaller model of infrared thermometer cone and to assess whether it is an appropriate alternative to determine fever in children under 14-years-old. METHOD: We performed a cross-sectional, descriptive study comparing the temperatures taken with a mercury thermometer with those taken by an infrared thermometer in children under 14-years-old. The researchers followed the manufacturer's instructions for use for each thermometer. The overall sample of 400 children was divided into two age groups. Group I consisted of children aged less than 2 years and group II of 2-14-years-old. In group I the rectal mercury thermometer was placed in the rectum for 3 minutes and the tympanic thermometer was used in rectal mode and placed in the right ear. In group II, the axillary mercury thermometer was placed for 8 minutes in the right axilla and the tympanic thermometer was used in the axillary mode. To analyze intraobserver bias, 50 patients were selected from the sample and their temperatures were simultaneously taken by two nurses from the team. The intraclass correlation coefficient (ICC) was used both to measure the reliability of the tympanic thermometer and to analyze intraobserver bias. RESULTS: Temperature measurements with both instruments showed an ICC of 0.91 (95% confidence interval [CI], 0.88-0.94) for group I and 0.90 (95% CI, 0.87-0.92) for group II. The reproducibility of the measurements taken by the two nurses in 50 patients showed an ICC of 0.97 (95% CI, 0.95-0.98) for the tympanic thermometer. CONCLUSIONS: The infrared thermometer is an appropriate device for rapidly measuring temperature in the emergency department. However, the measurements taken should be confirmed by another method when clinical decisions are based on temperature values.

[The association between bronchiectasis, systemic inflammation, and tumor necrosis factor alpha]. / Bronquiectasias, inflamación sistémica y factor de necrosis tumoral alfa: factores asociados.

OBJECTIVE: The relationship between systemic inflammation and different measures of bronchiectasis severity has not been described. The objective of this study was to analyze the relationship between plasma concentrations of tumor necrosis factor alpha (TNF-alpha), as a marker of systemic inflammation, and some commonly used criteria for quantifying bronchiectasis severity in clinically stable patients whose disease was not caused by cystic fibrosis. PATIENTS AND METHODS: Sixty-eight clinically stable patients with bronchiectasis and 19 age- and sex-matched healthy control subjects were included in the study. Data on disease history, symptoms, severity, functional variables, sputum volume, and microbiological cultures, laboratory findings, and other indicators of disease course were collected. Plasma concentrations of TNF-alpha were measured using high-resolution enzyme-linked immunoabsorbent assay. RESULTS: Plasma concentrations of TNF-alpha were higher in patients than controls (8.28 vs 5.67 pg/mL; P=.001). This observation correlated with other markers of systemic inflammation such as erythrocyte sedimentation rate (r=0.42; P=.001), C-reactive protein (rho=0.45; P=.001), and percentage of peripheral blood neutrophils (rho=0.45; P=.001). Patients with high plasma concentrations of TNF-alpha (>8.1 pg/dL) had more severe disease (5.19 vs 3.21; P=.001), were more likely to have respiratory failure (37.5% vs 8.3%; P=.003), and a higher rate of Pseudomonas aeruginosa colonization (34.3% vs 8.3%; P=.008). CONCLUSIONS: High plasma concentrations of TNF-alpha were associated with several criteria usually used to assess severity of bronchiectasis in clinically stable patients with disease not caused by cystic fibrosis.

Bronquiectasias, inflamación sistémica y factor de necrosis tumoral alfa: factores asociados / The association between bronchiectasis, systemic inflammation, and tumor necrosis factor alpha

Objetivo: La relación existente entre la presencia de inflamación sistémica y los diferentes parámetros de gravedad en pacientes con bronquiectasias no ha sido descrita. El objetivo del estudio ha sido analizar la relación entre las concentraciones plasmáticas de factor de necrosis tumoral alfa (pTNF-alfa), como marcador de inflamación sistémica, y algunos criterios de gravedad comúnmente utilizados en pacientes con bronquiectasias, en fase de estabilidad clínica, no debidas a fibrosis quística. Pacientes y métodos: Se incluyó en el estudio a 68 pacientes con bronquiectasias clínicamente estables y 19 controles sanos ajustados según edad y sexo. Se recogieron datos referentes a antecedentes patológicos, síntomas, extensión, variables funcionales, volumen de esputo y aspectos microbiológicos, analíticos y evolutivos. Las concentraciones de pTNF-alfa se analizaron utilizando un método de enzimoinmunoanálisis de alta resolución. Resultados: Se observó una mayor concentración de pTNF-alfa en los pacientes que en los controles (8,28 frente a 5,67 pg/ml; p = 0,001), que se correlacionó con otros parámetros de inflamación sistémica como la velocidad de sedimentación globular (r = 0,42; p = 0,001), la proteína C reactiva (r = 0,45; p = 0,001) y el porcentaje de neutrófilos periféricos (r = 0,45; p = 0,001). Los pacientes con concentraciones elevadas de pTNF-alfa (> 8,1 pg/dl) presentaron mayor extensión de la enfermedad (5,19 frente a 3,21; p = 0,001), mayor probabilidad de presentar insuficiencia respiratoria (el 37,5 frente al 8,3%; p = 0,003) y mayor porcentaje de colonizaciones por Pseudomonas aeruginosa (el 34,3 frente al 8,3%; p = 0,008). Conclusiones: Las concentraciones elevadas de pTNF-alfa se asocian a varios parámetros comúnmente utilizados para valorar la gravedad en pacientes con bronquiectasias clínicamente estables y no debidas a fibrosis quística

Objective: The relationship between systemic inflammation and different measures of bronchiectasis severity has not been described. The objective of this study was to analyze the relationship between plasma concentrations of tumor necrosis factor alpha (TNF-alpha), as a marker of systemic inflammation, and some commonly used criteria for quantifying bronchiectasis severity in clinically stable patients whose disease was not caused by cystic fibrosis. Patients and methods: Sixty-eight clinically stable patients with bronchiectasis and 19 age- and sex-matched healthy control subjects were included in the study. Data on disease history, symptoms, severity, functional variables, sputum volume, and microbiological cultures, laboratory findings, and other indicators of disease course were collected. Plasma concentrations of TNF-alpha were measured using high-resolution enzyme-linked immunoabsorbent assay. Results: Plasma concentrations of TNF-alpha were higher in patients than controls (8.28 vs 5.67 pg/mL; P=.001). This observation correlated with other markers of systemic inflammation such as erythrocyte sedimentation rate (r=0.42; P=.001), C-reactive protein (ñ=0.45; P=.001), and percentage of peripheral blood neutrophils (ñ=0.45; P=.001). Patients with high plasma concentrations of TNF-alpha (>8.1 pg/dL) had more severe disease (5.19 vs 3.21; P=.001), were more likely to have respiratory failure (37.5% vs 8.3%; P=.003), and a higher rate of Pseudomonas aeruginosa colonization (34.3% vs 8.3%; P=.008). Conclusions: High plasma concentrations of TNF-alpha were associated with several criteria usually used to assess severity of bronchiectasis in clinically stable patients with disease not caused by cystic fibrosis

[Decrease of serum cholinesterase in colorectal cancer]. / Disminución de la colinesterasa sérica en el cáncer colorrectal.

BACKGROUND AND OBJECTIVE: Cholinesterase is an enzyme with an unknown physiologic function. Some situations are related to a decreased serum cholinesterase activity but those situations are not well defined and the responsible mechanisms are unknown. Malignancy is one of these situations. The aim of the study was to compare the cholinesterase activity between patients with and without colorectal cancer. PATIENTS AND METHOD: Case-control study of patients with colorectal cancer who underwent surgery in our hospital from March 05 to January 07. RESULTS: Patients from the cancer group had a significant decreased serum cholinesterase activity. CONCLUSIONS: Investigation of cholinesterase function in humans may result in new research lines in oncology treatment.

[Bronchiectasis in the elderly. Study of serum levels of immunoglobulin G subclasses]. / Bronquiectasias en pacientes mayores de 65 años. Estudio de los valores séricos de las subclases de inmunoglobulina G.

BACKGROUND AND OBJECTIVE: To analyze the serum levels of immunoglobulin G (IgG) subclasses in a broad range of elderly patients with bronchiectasis. PATIENTS AND METHOD: Data were collected from all patients who had a high-resolution chest computerized axial tomography diagnosis of bronchiectasis in our center. We gathered data related to case history, respiratory symptoms, forced spirometry, general laboratory tests, immunoglobulin concentration (including IgG subclasses), Mantoux test, sputum culture and staining, paranasal sinus X-rays/computerized axial tomography, and a specific etiologic evaluation based on the available clinical evidence. RESULTS: A total of 128 patients were included -mean age (standard deviation): 71.6 (5.1) years; range: 65-88; 44.5% males- and 20.3% of them had chronic sputum colonization with Pseudomonas aeruginosa. 28.1% cases had a post-infectious nature and in 40.6% the etiology was unknown. Sixteen patients (12.5%) had decreased levels of at least one of the sIgG compared to normal values. The most frequent deficiency corresponded to IgG2 levels. These subjects showed a characteristic profile of bronchiectasis with an increased lung extension of the disease (p = 0.02); greater presence of cylindrical and diffuse bronchiectasis (p = 0.02 and 0.01, respectively), greater percentage of an unknown etiology (p = 0.004); greater presence of paranasal sinus X-ray abnormalities (p = 0.004) and increased number of past repeated upper airway infections (p = 0.03). CONCLUSIONS: Decreased serum levels of IgG subclasses might be associated with a characteristic profile of bronchiectasis in elderly patients in whom other etiologies have been ruled out.

Disminución de la colinesterasa sérica en el cáncer colorrectal / Decrease of serum cholinesterase in colorectal cancer

Fundamento y objetivo: La colinesterasa es una enzima cuya función fisiológica se ignora. Hay diversas situaciones donde su actividad disminuye, pero aún no están bien definidas y se desconocen los mecanismos responsables. Una de estas situaciones es la presencia de malignidad. El objetivo de este estudio ha sido comparar la actividad de la colinesterasa en pacientes con y sin cáncer colorrectal. Pacientes y método: Se ha realizado un estudio de casos y controles, en el que se ha incluido a pacientes operados de carcinoma colorrectal en nuestro servicio entre marzo de 2005 y enero de 2007. Resultados: El grupo de cáncer presentó una disminución significativa de los valores séricos de actividad de colinesterasa. Conclusiones: El estudio de la función de la colinesterasa en el organismo humano puede ser útil en la génesis de nuevas líneas de investigación en tratamiento oncológico

Background and objective: Cholinesterase is an enzyme with an unknown physiologic function. Some situations are related to a decreased serum cholinesterase activity but those situations are not well defined and the responsible mechanisms are unknown. Malignancy is one of these situations. The aim of the study was to compare the cholinesterase activity between patients with and without colorectal cancer. Patients and method: Case-control study of patients with colorectal cancer who underwent surgery in our hospital from March 05 to January 07. Results: Patients from the cancer group had a significant decreased serum cholinesterase activity. Conclusions: Investigation of cholinesterase function in humans may result in new research lines in oncology treatment

Bronquiectasias en pacientes mayores de 65 años. Estudio de los valores séricos de las subclases de inmunoglobulina G / Bronchiectasis in the elderly. Study of serum levels of immunoglobulin G subclasses

Fundamento y objetivo: Analizar los valores séricos de las subclases de inmunoglobulina G (IgG) en un amplio número de pacientes mayores de 65 años con bronquiectasias. Pacientes y método: De todos los pacientes mayores de 65 años diagnosticados en nuestro centro de bronquiectasias mediante tomografía computarizada de alta resolución de tórax, se recogieron de forma prospectiva datos relativos a la historia clínica, síntomas, espirometría forzada, estudio analítico, determinación de la concentración de inmunoglobulinas, incluidas las subclases de IgG, Mantoux, tinción y cultivo de esputo, radiografía/tomografía computarizada de senos paranasales y estudio etiológico específico según sospecha clínica. Resultados: Se incluyó en el estudio a 128 pacientes, con una edad media (desviación estándar) de 71,6 (5,1) años (extremos: 65-88 años); un 44,5% eran varones. El 20,3% presentó colonización crónica por Pseudomonas aeruginosa. La causa conocida más frecuente de bronquiectasias fue la infecciosa (28,1%), si bien el 40,6% permaneció con etiología desconocida. Dieciséis pacientes (12,5%) presentaron alguna disminución de los valores séricos de las subclases de IgG respecto a los valores de normalidad, siendo la más frecuente la disminución de los valores de IgG2. Estos pacientes mostraron un perfil de bronquiectasias peculiar: de forma significativa, presentaron una mayor extensión pulmonar (p = 0,02), mayor porcentaje de formas difusas y cilíndricas (p = 0,02 y 0,01, respectivamente), mayor porcentaje de formas con etiología no conocida (p = 0,004), mayor afectación de los senos paranasales (p = 0,004) y mayor prevalencia pasada de infecciones respiratorias de las vías altas de repetición (p = 0,03). Conclusiones: La disminución de los valores séricos de las subclases de IgG podría asociarse a la aparición de bronquiectasias con un perfil peculiar en pacientes mayores de 65 años en los que se ha descartado otra posible causa

Background and objective: To analyze the serum levels of immunoglobulin G (IgG) subclasses in a broad range of elderly patients with bronchiectasis. Patientes and method: Data were collected from all patients who had a high-resolution chest computerized axial tomography diagnosis of bronchiectasis in our center. We gathered data related to case history, respiratory symptoms, forced spirometry, general laboratory tests, immunoglobulin concentration (including IgG subclasses), Mantoux test, sputum culture and staining, paranasal sinus X-rays/computerized axial tomography, and a specific etiologic evaluation based on the available clinical evidence. Results: A total of 128 patients were included ­mean age (standard deviation): 71.6 (5.1) years; range: 65-88; 44.5% males­ and 20.3% of them had chronic sputum colonization with Pseudomonas aeruginosa. 28.1% cases had a post-infectious nature and in 40.6% the etiology was unknown. Sixteen patients (12.5%) had decreased levels of at least one of the sIgG compared to normal values. The most frequent deficiency corresponded to IgG2 levels. These subjects showed a characteristic profile of bronchiectasis with an increased lung extension of the disease (p = 0.02); greater presence of cylindrical and diffuse bronchiectasis (p = 0.02 and 0.01, respectively), greater percentage of an unknown etiology (p = 0.004); greater presence of paranasal sinus X-ray abnormalities (p = 0.004) and increased number of past repeated upper airway infections (p = 0.03) Conclusions: Decreased serum levels of IgG subclasses might be associated with a characteristic profile of bronchiectasis in elderly patients in whom other etiologies have been ruled out