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1.
Pediatr Dev Pathol ; 24(2): 131-136, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33439110

RESUMEN

STAT1 gain-of-function (GOF) mutations are associated with a rare autosomal dominant immunodeficiency disorder with main clinical manifestations including chronic mucocutaneous candidiasis (CMC) and bronchiectasis. In addition, these patients show higher incidences of cerebral and extracerebral aneurysm, malignancies and various autoimmune conditions compared to the general population. Although previous publications have reported clinical findings in patients with STAT1 GOF mutation, they did not include histopathologic features. Herein, we describe the first case with detailed histologic findings in the lung of a 5-year-old patient with a de novo STAT1 GOF mutation, who presented with CMC and bronchiectasis. The biopsy showed severe bronchiolectasis with extensive airway dilatation and occasional disruptions. Peribronchiolar inflammation was not always present and evident mainly in areas of airway disruption; inflammation may have not been a main driver of the airway damage in this case. The airway dilatation often showed an interesting herniating pattern, possibly implying a connective tissue etiology. This case also demonstrates the diagnostic utility of whole exome sequencing as STAT1 GOF mutations are not detected by routine workup. The definitive diagnosis will lead to more specific treatments and increased surveillance for serious conditions, such as cerebral aneurysms and malignancies.


Asunto(s)
Bronquiectasia/diagnóstico , Mutación con Ganancia de Función , Factor de Transcripción STAT1/genética , Bronquiectasia/complicaciones , Bronquiectasia/genética , Bronquiectasia/patología , Candidiasis Mucocutánea Crónica/complicaciones , Candidiasis Mucocutánea Crónica/diagnóstico , Candidiasis Mucocutánea Crónica/genética , Candidiasis Mucocutánea Crónica/patología , Preescolar , Femenino , Marcadores Genéticos , Humanos , Secuenciación del Exoma
2.
Can J Physiol Pharmacol ; 99(3): 328-331, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33657328

RESUMEN

A total of 115 convalescent inpatients with COVID-19 were enrolled. According to the results of scans of lung lesions via computed tomography (CT), the patients were divided into mild, moderate, and severe groups. The clinical data of the patients were collected, including age, gender, finger pulse oxygen pressure, ventricular rate, body temperature, etc. The correlation between the clinical indicators and the lesions of high-resolution CT (HRCT) and bronchiectasis was analyzed. Among the 115 patients, 82 had no bronchiectasis and 33 had bronchiectasis. The bronchodilation-prone layers mainly included the left and right lower lobe of the lung. The probability of branching in the inflamed area was greater than that in the noninflamed area in patients with COVID-19. There were significant differences in gender, CT lesion range, and number of incidents of bronchiectasis between noninflamed and inflamed areas (P < 0.05). Moreover, there were significant differences in age, total proportion of CT lesions, volume of CT lesions, and total number of patients with bronchiectasis among the three groups (P < 0.05). CT lesion range was positively correlated with the total number of patients with bronchiectasis and patient age (respectively, r = 0.186, P < 0.05; r = 0.029, P < 0.05). The lesion range in HRCT images of lungs in patients with COVID-19 is correlated with bronchodilation. The larger the lesion, the higher the probability of bronchiectasis and the more incidents of bronchiectasis.


Asunto(s)
Bronquiectasia/patología , Bronquiectasia/virología , COVID-19/patología , COVID-19/virología , Pulmón/patología , Pulmón/virología , Neumonía/patología , Neumonía/virología , Adulto , Femenino , Humanos , Masculino , Estudios Retrospectivos , SARS-CoV-2/patogenicidad , Índice de Severidad de la Enfermedad , Tomografía Computarizada por Rayos X/métodos
3.
Int J Mol Sci ; 22(11)2021 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-34206113

RESUMEN

Airway inflammation plays a central role in bronchiectasis. Protease-antiprotease balance is crucial in bronchiectasis pathophysiology and increased presence of unopposed proteases activity may contribute to bronchiectasis onset and progression. Proteases' over-reactivity and antiprotease deficiency may have a role in increasing inflammation in bronchiectasis airways and may lead to extracellular matrix degradation and tissue damage. Imbalances in serine proteases and matrix-metallo proteinases (MMPs) have been associated to bronchiectasis. Active neutrophil elastase has been associated with disease severity and poor long-term outcomes in this disease. Moreover, high levels of MMPs have been associated with radiological and disease severity. Finally, severe deficiency of α1-antitrypsin (AAT), as PiSZ and PiZZ (proteinase inhibitor SZ and ZZ) phenotype, have been associated with bronchiectasis development. Several treatments are under study to reduce protease activity in lungs. Molecules to inhibit neutrophil elastase activity have been developed in both oral or inhaled form, along with compounds inhibiting dipeptydil-peptidase 1, enzyme responsible for the activation of serine proteases. Finally, supplementation with AAT is in use for patients with severe deficiency. The identification of different targets of therapy within the protease-antiprotease balance contributes to a precision medicine approach in bronchiectasis and eventually interrupts and disrupts the vicious vortex which characterizes the disease.


Asunto(s)
Bronquiectasia/metabolismo , Péptido Hidrolasas/metabolismo , Inhibidores de Proteasas/metabolismo , Deficiencia de alfa 1-Antitripsina/metabolismo , Bronquiectasia/enzimología , Bronquiectasia/genética , Bronquiectasia/patología , Humanos , Elastasa de Leucocito , Pulmón/metabolismo , Pulmón/patología , Metaloproteinasas de la Matriz/genética , Metaloproteinasas de la Matriz/metabolismo , Neutrófilos/metabolismo , Neutrófilos/patología , Serina Proteasas/genética , Serina Proteasas/metabolismo , Deficiencia de alfa 1-Antitripsina/genética , Deficiencia de alfa 1-Antitripsina/patología
4.
Turk J Med Sci ; 51(2): 631-637, 2021 04 30.
Artículo en Inglés | MEDLINE | ID: mdl-33081435

RESUMEN

Background/aim: Two different scoring systems were developed to determine the severity of bronchiectasis: FACED scoring and the bronchiectasis severity index (BSI). In this study, we aim to compare these 2 scoring systems according to the 6-min walking distance test and a disease-specific health status questionnaire in patients with noncystic fibrosis bronchiectasis (NCFB). Materials and methods: Smoking history, emergency and hospital admissions, and body mass index were obtained from NCFB patients admitted to our hospitals' pulmonary rehabilitation unit between 2013 and 2018. Detailed pulmonary function tests were performed for all participants. Dyspnea perceptions were determined according to the mMRC dyspnea scale. The 6-min walking test was used to determine exercise capacity. The Saint George respiratory questionnaire (SGRQ) was applied to determine health status. Both FACED and BSI scores were calculated for all participants. Results: There were a total of 183 participants, 153 of whom were men. A significant and strong correlation was found between FACED and BSI scores. As the severity of bronchiectasis increased, walking distance was significantly decreased and health status was significantly worse in both FACED and BSI scoring. A statistically significant but weak negative correlation was found between FACED score and walking distance. There was a significant negative correlation between BSI and walking distance, a stronger negative correlation than with FACED. Similarly, there was a significant negative correlation between health status and both FACED and BSI, but this correlation was stronger in the BSI score. Conclusions: Although both FACED and BSI scores were negatively correlated with walking distance and health status in patients with NCFB, BSI was more strongly associated.


Asunto(s)
Bronquiectasia/fisiopatología , Prueba de Esfuerzo/métodos , Tolerancia al Ejercicio/fisiología , Caminata/fisiología , Adulto , Anciano , Bronquiectasia/patología , Femenino , Fibrosis/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Consumo de Oxígeno
5.
Curr Opin Infect Dis ; 33(2): 189-196, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31990814

RESUMEN

PURPOSE OF REVIEW: Pulmonary exacerbations are key events in the natural history of bronchiectasis given their impact on quality of life, prognosis, and their contribution to healthcare costs. Preventing and managing exacerbations is a priority for clinicians and in this review, we discuss measures that should be utilized to achieve this aim. RECENT FINDINGS: Experts have proposed a focus on phenotyping and endotyping the bronchiectasis population to overcome the heterogeneity of this condition. Recent large studies of inhaled antibiotics and smaller studies of macrolides, which included exacerbation measures as their primary outcomes, have drawn further attention to this issue. SUMMARY: Exacerbations are currently treated with prolonged antibiotic treatment (10-14 days). Prevention of exacerbations requires a multidisciplinary approach which includes optimising airway clearance and treating underlying conditions. Patients who continue to experience exacerbations despite these measures may be offered chronic macrolide therapy or additional therapies based on identified treatable traits.


Asunto(s)
Bronquiectasia/patología , Bronquiectasia/terapia , Antibacterianos/uso terapéutico , Expectorantes/uso terapéutico , Humanos , Modalidades de Fisioterapia
6.
Rev Med Suisse ; 16(698): 1250-1255, 2020 Jun 17.
Artículo en Francés | MEDLINE | ID: mdl-32558454

RESUMEN

Allergic bronchopulmonary aspergillosis (ABPA) is a specific complex immunological response to the spores of Aspergillus fumigatus (Af) colonizing the bronchi of asthmatic or cystic fibrosis patients. Recurrent episodes of bronchial obstruction and inflammation, as well as mucoid impaction cause bronchiectasis, pulmonary infiltrates and fibrotic alterations of the lung parenchyma, resulting in significant morbidity and mortality. The pathogenesis of ABPA remains incompletely understood, so it is not clear why certain colonized subjects develop hypersensitivity to Af, and why some sensitized patients develop ABPA and others do not. There is no simple and specific test for diagnosing ABPA. The diagnosis is based on the combination of clinical, radiological and immunological criteria. Systemic steroids are the cornerstone of treatment.


L'aspergillose bronchopulmonaire allergique (ABPA) est une réponse immunologique spécifique complexe contre les spores d'Aspergillus fumigatus (Af) qui colonisent les bronches de patients asthmatiques ou mucoviscidosiques. Les épisodes répétés d'obstruction et d'inflammation bronchiques et d'impactions mucoïdes génèrent des bronchiectasies, des infiltrats pulmonaires et des altérations fibrotiques du parenchyme pulmonaire, d'où une morbi-mortalité significative. La pathogenèse de l'ABPA reste mal comprise, si bien qu'on ne sait pas véritablement pourquoi certains sujets colonisés développent une hypersensibilité à Af, et pourquoi certains patients sensibilisés développent une ABPA et d'autres pas. Il n'y a pas de test simple et spécifique qui permette de diagnostiquer une ABPA. Le diagnostic se base sur l'association de critères cliniques, radiologiques et immunologiques. Les stéroïdes systémiques sont la pierre angulaire du traitement.


Asunto(s)
Aspergilosis Broncopulmonar Alérgica , Aspergilosis Broncopulmonar Alérgica/diagnóstico , Aspergilosis Broncopulmonar Alérgica/tratamiento farmacológico , Aspergilosis Broncopulmonar Alérgica/inmunología , Aspergilosis Broncopulmonar Alérgica/patología , Aspergillus fumigatus/inmunología , Asma/inmunología , Asma/patología , Bronquiectasia/inmunología , Bronquiectasia/patología , Humanos , Pulmón/patología
7.
J Clin Immunol ; 39(1): 45-54, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30547383

RESUMEN

Studies of chest computed tomography (CT) in patients with primary antibody deficiency syndromes (ADS) suggest a broad range of bronchial pathology. However, there are as yet no multicentre studies to assess the variety of bronchial pathology in this patient group. One of the underlying reasons is the lack of a consensus methodology, a prerequisite to jointly document chest CT findings. We aimed to establish an international platform for the evaluation of bronchial pathology as assessed by chest CT and to describe the range of bronchial pathologies in patients with antibody deficiency. Ffteen immunodeficiency centres from 9 countries evaluated chest CT scans of patients with ADS using a predefined list of potential findings including an extent score for bronchiectasis. Data of 282 patients with ADS were collected. Patients with common variable immunodeficiency disorders (CVID) comprised the largest subgroup (232 patients, 82.3%). Eighty percent of CVID patients had radiological evidence of bronchial pathology including bronchiectasis in 61%, bronchial wall thickening in 44% and mucus plugging in 29%. Bronchiectasis was detected in 44% of CVID patients aged less than 20 years. Cough was a better predictor for bronchiectasis than spirometry values. Delay of diagnosis as well as duration of disease correlated positively with presence of bronchiectasis. The use of consensus diagnostic criteria and a pre-defined list of bronchial pathologies allows for comparison of chest CT data in multicentre studies. Our data suggest a high prevalence of bronchial pathology in CVID due to late diagnosis or duration of disease.


Asunto(s)
Bronquios/patología , Síndromes de Inmunodeficiencia/patología , Pared Torácica/patología , Adolescente , Adulto , Anciano , Bronquiectasia/patología , Niño , Preescolar , Inmunodeficiencia Variable Común/patología , Femenino , Humanos , Lactante , Masculino , Espirometría/métodos , Tomografía Computarizada por Rayos X/métodos , Adulto Joven
8.
Eur Respir J ; 54(5)2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31467117

RESUMEN

The pathophysiological processes underlying bronchiectasis in chronic obstructive pulmonary disease (COPD) are not understood. In COPD, both small and large airways are progressively lost. It is currently not known to what extent the different airway generations of patients with COPD and bronchiectasis are involved.COPD explant lungs with bronchiectasis were compared to COPD explant lungs without bronchiectasis and unused donor lungs as controls. In order to investigate all airway generations, a multimodal imaging approach using different resolutions was conducted. Per group, five lungs were frozen (n=15) and underwent computed tomography (CT) imaging for large airway evaluation, with four tissue cores per lung imaged for measurements of the terminal bronchioles. Two additional lungs per group (n=6) were air-dried for lobar microCT images that allow airway segmentation and three-dimensional quantification of the complete airway tree.COPD lungs with bronchiectasis had significantly more airways compared to COPD lungs without bronchiectasis (p<0.001), with large airway numbers similar to control lungs. This difference was present in both upper and lower lobes. Lack of tapering was present (p=0.010) and larger diameters were demonstrated in lower lobes with bronchiectasis (p=0.010). MicroCT analysis of tissue cores showed similar reductions of tissue percentage, surface density and number of terminal bronchioles in both COPD groups compared to control lungs.Although terminal bronchioles were equally reduced in COPD lungs with and without bronchiectasis, significantly more large and small airways were found in COPD lungs with bronchiectasis.


Asunto(s)
Bronquiectasia/diagnóstico por imagen , Bronquiectasia/patología , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico por imagen , Enfermedad Pulmonar Obstructiva Crónica/patología , Tomografía Computarizada por Rayos X , Anciano , Bronquiolos/diagnóstico por imagen , Bronquiolos/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
9.
Eur Respir J ; 54(1)2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31023850

RESUMEN

INTRODUCTION: Pulmonary inflammation and infection are important clinical and prognostic markers of lung disease in cystic fibrosis (CF). However, whether in young children they are transient findings or have cumulative, long-term impacts on respiratory health is largely unknown. We aimed to determine whether their repeated detection has a deleterious effect on structural lung disease. METHODS: All patients aged <6 years with annual computed tomography (CT) and bronchoalveolar lavage (BAL) were included. Structural lung disease on CT (%Disease) was determined using the PRAGMA-CF (Perth-Rotterdam Annotated Grid Morphometric Analysis for CF) method. The number of times free neutrophil elastase (NE) and infection were detected in BAL were counted, to determine cumulative BAL history. Linear mixed model analysis, accounting for repeat visits and adjusted for age, was used to determine associations. RESULTS: 265 children (683 scans) were included for analysis, with BAL history comprising 1161 visits. %Disease was significantly associated with the number of prior NE (0.31, 95% CI 0.09-0.54; p=0.007) but not infection (0.23, 95% CI -0.01-0.47; p=0.060) detections. Reference equations were determined. CONCLUSIONS: Pulmonary inflammation in surveillance BAL has a cumulative effect on structural lung disease extent, more so than infection. This provides a strong rationale for therapies aimed at reducing inflammation in young children.


Asunto(s)
Bronquiectasia/diagnóstico por imagen , Líquido del Lavado Bronquioalveolar/química , Fibrosis Quística/diagnóstico por imagen , Pulmón/diagnóstico por imagen , Bronquiectasia/patología , Preescolar , Ensayos Clínicos como Asunto , Fibrosis Quística/patología , Progresión de la Enfermedad , Femenino , Humanos , Lactante , Elastasa de Leucocito/análisis , Pulmón/patología , Masculino , Variaciones Dependientes del Observador , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad , Tomografía Computarizada por Rayos X , Australia Occidental
10.
Respir Res ; 20(1): 271, 2019 Dec 03.
Artículo en Inglés | MEDLINE | ID: mdl-31796019

RESUMEN

BACKGROUND: All-cause mortality risk and causes of death in bronchiectasis patients have not been fully investigated. The aim of this study was to compare the mortality risk and causes of death between individuals with bronchiectasis and those without bronchiectasis. METHODS: Patients with or without bronchiectasis determined based on chest computed tomography (CT) at one centre between 2005 and 2016 were enrolled. Among the patients without bronchiectasis, a control group was selected after applying additional exclusion criteria. We compared the mortality risk and causes of death between the bronchiectasis and control groups without lung disease. Subgroup analyses were also performed according to identification of Pseudomonas or non-tuberculous mycobacteria, airflow limitation, and smoking status. RESULTS: Of the total 217,702 patients who underwent chest CT, 18,134 bronchiectasis patients and 90,313 non-bronchiectasis patients were included. The all-cause mortality rate in the bronchiectasis group was 1608.8 per 100,000 person-years (95% confidence interval (CI), 1531.5-1690.0), which was higher than that in the control group (133.5 per 100,000 person-years; 95% CI, 124.1-143.8; P < 0.001). The bronchiectasis group had higher all-cause (adjusted hazard ratio (aHR), 1.26; 95% CI, 1.09-1.47), respiratory (aHR, 3.49; 95% CI, 2.21-5.51), and lung cancer-related (aHR, 3.48; 95% CI, 2.33-5.22) mortality risks than the control group. In subgroup analysis, patients with airflow limitation and ever smokers showed higher all-cause mortality risk among bronchiectasis patients. Therefore, we observed significant interrelation between bronchiectasis and smoking, concerning the risks of all-cause mortality (P for multiplicative interaction, 0.030, RERI, 0.432; 95% CI, 0.097-0.769) and lung cancer-related mortality (RERI, 8.68; 95% CI, 1.631-15.736). CONCLUSION: Individuals with bronchiectasis had a higher risk of all-cause, respiratory, and lung cancer-related mortality compared to control group. The risk of all-cause mortality was more prominent in those with airflow limitation and in ever smokers.


Asunto(s)
Bronquiectasia/diagnóstico por imagen , Bronquiectasia/mortalidad , Causas de Muerte , Neoplasias Pulmonares/mortalidad , Adulto , Bronquiectasia/patología , Estudios de Casos y Controles , Fibrosis Quística , Femenino , Fibrosis/mortalidad , Fibrosis/patología , Hospitales Universitarios , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Radiografía Torácica/métodos , Valores de Referencia , República de Corea , Pruebas de Función Respiratoria , Estudios Retrospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Tomografía Computarizada por Rayos X/métodos , Adulto Joven
11.
Eur J Clin Microbiol Infect Dis ; 38(2): 373-381, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30552538

RESUMEN

Mycobacterium xenopi pulmonary disease (Mxe-PD) is common among nontuberculous mycobacterial infections in Europe and Canada. Associations between radiological pattern and clinical features and outcomes are inadequately studied in Mxe-PD. We sought to investigate clinical characteristics and outcomes according to the dominant radiological pattern among patients with Mxe-PD. We retrospectively studied patients with Mxe-PD seen in our clinic, categorizing their predominant CT pattern as nodular bronchiectasis, fibrocavitary, or unclassifiable, and compared clinical characteristics, treatment, and outcomes between radiologic groups. Of 94 patients with Mxe-PD, CT patterns comprised nodular bronchiectasis (40/94, 42.6%), fibrocavitary (37/94, 39.4%), and unclassifiable (17/94, 18.1%). Compared with fibrocavitation, patients with nodular bronchiectasis were female dominant, less often had COPD, less often had AFB smear-positive sputum, and more frequently had co-isolation of Pseudomonas. Patients with nodular bronchiectasis were less often treated (65% versus 91.9%) and when treated, they received fewer anti-mycobacterial drugs (on average 3 versus 4). Outcomes did not differ significantly by radiological pattern. Nodular bronchiectasis was common among Mxe-PD patients in our clinic. Compared with fibrocavitary disease, patients with nodular bronchiectasis had features suggestive of milder disease and were less often treated. Among treated patients, outcomes did not differ by radiologic pattern.


Asunto(s)
Enfermedades Pulmonares/diagnóstico por imagen , Enfermedades Pulmonares/patología , Infecciones por Mycobacterium no Tuberculosas/diagnóstico por imagen , Infecciones por Mycobacterium no Tuberculosas/patología , Mycobacterium xenopi/aislamiento & purificación , Tomografía Computarizada por Rayos X , Anciano , Bronquiectasia/diagnóstico por imagen , Bronquiectasia/tratamiento farmacológico , Bronquiectasia/patología , Femenino , Humanos , Enfermedades Pulmonares/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Pronóstico , Estudios Retrospectivos
12.
Clin Lab ; 65(9)2019 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-31532086

RESUMEN

BACKGROUND: G-lipopolysaccharide, a component of the cell wall of Gram-negative bacteria, is called lipopolysaccharide. The detection of G-lipopolysaccharide can be used for the early diagnosis of infectious diseases, but some-times G-lipopolysaccharide provides limited help. We report a case of a patient with hemoptysis and high-density shadow of both lungs combined with elevated serum G-lipopolysaccharide which mimicked bronchiectasis with Gram-negative bacterium infection. It was ultimately confirmed as Mycobacterium iranicum infection by CT-guided percutaneous lung biopsy and next generation sequencing. METHODS: The chest computed tomography (CT) scan, CT-guided percutaneous lung biopsy, and NGS were performed for diagnosis and blood tests explored for the latent etiology. RESULTS: The chest CT scan showed a high-density shadow of both lungs, atelectasis of right middle lobe, multiple enlarged lymph nodes in mediastinum and right hilum. Pathology of CT-guided percutaneous lung biopsy indicated fibrous tissue proliferation and granulation tissue formation and some alveolar epithelial cells slightly proliferated with focal carbon powder deposition in alveolar sacs and spaces. The lung tissue NGS confirmed Mycobacterium iranicum infection. CONCLUSIONS: Elevated serum G-lipopolysaccharide is not a specific index for infectious diseases. CT-guided percutaneous lung biopsy and lung tissue NGS has high specificity in pathogen detection of infectious diseases.


Asunto(s)
Bronquiectasia/patología , Infecciones por Bacterias Gramnegativas/diagnóstico , Hemoptisis/diagnóstico , Lipopolisacáridos/sangre , Pulmón/patología , Infecciones por Mycobacterium/diagnóstico , Anciano , Biopsia/métodos , Diagnóstico Diferencial , Errores Diagnósticos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Pulmón/microbiología , Masculino , Tomografía Computarizada por Rayos X
13.
Med Sci Monit ; 25: 6805-6811, 2019 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-31503552

RESUMEN

BACKGROUND The prevalence of bronchiectasis with comorbid chronic obstructive pulmonary disease (COPD) is rising, which causes extremely high risk of exacerbation and mortality. We aimed to evaluate the differences in clinicopathological manifestations, immune function, and inflammation in bronchiectasis patients with comorbid COPD vs. patients who only have COPD. MATERIAL AND METHODS Clinicopathological characteristics, including common potentially pathogenic microorganisms, lung function, immune function, and inflammation were assessed in bronchiectasis patients with comorbid COPD and in patients who only had COPD. RESULTS Compared to patients who only had COPD, patients with bronchiectasis with comorbid COPD had a higher positive rate of sputum bacteria (45.27% vs. 28.03%, P<0.01). Among them, Pseudomonas aeruginosa (P. aeruginosa) accounted for 25.19% in COPD (4.37%) (P<0.01). Likewise, patients with bronchiectasis with comorbid COPD had worse lung function, worse COPD assessment test scores, and worse Modified Medical Research Council scores. Moreover, compared with COPD only cases, patients with bronchiectasis with comorbid COPD had higher levels of white blood cells (WBC), neutrophils, C-reactive protein (CRP), and procalcitonin (PCT) (all P<0.05). Interestingly, the expression levels of Treg in patients with bronchiectasis with comorbid COPD were lower than in patients with COPD only (P<0.05). Th17 and Th17/Treg levels were higher (P<0.05). Furthermore, remarkable increased level of IL17 and IL-6 and decreased level of IL-10 and TGF-ß were observed in the bronchiectasis combined COPD than in pure COPD (All P<0.05). CONCLUSIONS Our findings suggest that P. aeruginosa is the main pathogen of bacterial infection in bronchiectasis patients with comorbid COPD. These patients have more serious clinical manifestations and immune imbalance, which should be considered when providing clinical treatment.


Asunto(s)
Bronquiectasia/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Biomarcadores/metabolismo , Bronquiectasia/inmunología , Bronquiectasia/patología , Bronquiectasia/fisiopatología , China/epidemiología , Comorbilidad , Progresión de la Enfermedad , Femenino , Humanos , Inflamación/patología , Masculino , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Enfermedad Pulmonar Obstructiva Crónica/patología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Pruebas de Función Respiratoria , Esputo
14.
Curr Opin Infect Dis ; 31(2): 194-198, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29489526

RESUMEN

PURPOSE OF REVIEW: Bronchiectasis, once thought to be an orphan disease, is being diagnosed with increased frequency in the United States and around the world. The present review aims to provide an update on recent publications on the diagnosis and management of bronchiectasis. RECENT FINDINGS: Two large bronchiectasis patient registries have published initial reports regarding demographics and other patient data in 2017. Updates on the microbiology, microbiome, and inflammation in patients with bronchiectasis are clarifying the complexities of airway infection in this disease. A consensus definition of 'exacerbation' in bronchiectasis has been agreed upon this year. Reports on novel treatments, including the repurposing of older therapies, have also been published in 2016-2017. A new European guideline for the management of adult bronchiectasis is also now available. SUMMARY: Bronchiectasis, a resurgent disease, is now being better defined with a rapidly expanding portfolio of demographic, clinical, and therapeutic research and publications.


Asunto(s)
Bronquiectasia/diagnóstico , Bronquiectasia/terapia , Manejo de la Enfermedad , Factores de Edad , Bronquiectasia/epidemiología , Bronquiectasia/patología , Salud Global , Humanos , Prevalencia
15.
Int J Mol Sci ; 19(11)2018 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-30380761

RESUMEN

Cytokines are key players in the initiation and propagation of inflammation in chronic inflammatory airway diseases such as chronic obstructive pulmonary disease (COPD), bronchiectasis and allergic asthma. This makes them attractive targets for specific novel anti-inflammatory treatment strategies. Recently, both interleukin-1 (IL-1) and IL-6 have been associated with negative health outcomes, mortality and a pro-inflammatory phenotype in COPD. IL-6 in COPD was shown to correlate negatively with lung function, and IL-1beta was induced by cigarette smoke in the bronchial epithelium, causing airway inflammation. Furthermore, IL-8 has been shown to be a pro-inflammatory marker in bronchiectasis, COPD and allergic asthma. Clinical trials using specific cytokine blockade therapies are currently emerging and have contributed to reduce exacerbations and steroid use in COPD. Here, we present a review of the current understanding of the roles of cytokines in the pathophysiology of chronic inflammatory airway diseases. Furthermore, outcomes of clinical trials in cytokine blockade as novel treatment strategies for selected patient populations with those diseases will be discussed.


Asunto(s)
Asma , Bronquiectasia , Citocinas/antagonistas & inhibidores , Enfermedad Pulmonar Obstructiva Crónica , Mucosa Respiratoria , Animales , Asma/inmunología , Asma/patología , Asma/terapia , Bronquiectasia/inmunología , Bronquiectasia/patología , Bronquiectasia/terapia , Citocinas/inmunología , Humanos , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Enfermedad Pulmonar Obstructiva Crónica/patología , Enfermedad Pulmonar Obstructiva Crónica/terapia , Mucosa Respiratoria/inmunología , Mucosa Respiratoria/patología
16.
Crit Rev Microbiol ; 43(4): 508-519, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28068853

RESUMEN

One of the most common and most severe forms of primary antibody deficiency encountered in the clinical setting is a heterogeneous group of syndromes termed common variable immune deficiency (CVID). This disorder is characterized by reduced immunoglobulin production and increased susceptibility to infection, particularly of the respiratory tract. Infection and subsequent immunological/inflammatory processes may contribute to the development of pulmonary complications such as bronchiectasis and interstitial lung disease. Immunoglobulin replacement and/or antibiotic therapy, to prevent infection, are routinely prescribed treatments. However, chronic lung disease, the major cause of morbidity and mortality in this patient cohort, may still progress. This clinical progression suggests that pathogens recalcitrant to currently prescribed treatments and other immunological defects may be contributing to the development of pulmonary disease. This review describes the potential role of microbiological and non-B cell immunological factors, including T-cells, neutrophils, complement, toll like receptors, and antimicrobial peptides, in the pathogenicity of chronic lung disease in patients with CVID.


Asunto(s)
Infecciones Bacterianas/patología , Bronquiectasia/patología , Inmunodeficiencia Variable Común/patología , Enfermedades Pulmonares Intersticiales/patología , Infecciones del Sistema Respiratorio/patología , Virosis/patología , Antibacterianos/uso terapéutico , Infecciones Bacterianas/inmunología , Bronquiectasia/inmunología , Enfermedad Crónica , Inmunodeficiencia Variable Común/diagnóstico , Proteínas del Sistema Complemento/inmunología , Progresión de la Enfermedad , Humanos , Factores Inmunológicos/inmunología , Enfermedades Pulmonares Intersticiales/inmunología , Neutrófilos/inmunología , Infecciones del Sistema Respiratorio/inmunología , Infecciones del Sistema Respiratorio/microbiología , Linfocitos T/inmunología , Virosis/inmunología
17.
J Assist Reprod Genet ; 34(2): 275-281, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27988889

RESUMEN

PURPOSE: Kartagener syndrome (KS), also known as visceral inversion-nasosinusitis-bronchiectasis syndrome, or familial bronchiectasis, is an autosomal recessive inherited disease. In this study, through two cases of KS, we aimed to assess the clinical and genetic characteristics of KS caused by DNAH5 mutations. METHODS: The two cases of KS from the same family underwent extensive clinical assessments, with next-generation DNA sequencing and bioinformatics analysis to identify pathogenic genes. In addition, Sanger sequencing was used to verify the pedigrees. RESULTS: The present study employed a directional capture strategy for hereditary disease screening, which correctly identified the virulence sites in the pedigree, and facilitated the differential diagnosis among multiple genes. Two novel mutations were detected in DNAH5: c.7778C>T (missense mutation) and c.13729G>A (nonsense mutation). They were not found in dbSNP, 1000 Genomes, and ExAC. CONCLUSIONS: These findings demonstrated that new DNAH5 mutations could be used for molecular diagnosis of KS, providing families with genetic counseling and prenatal diagnosis.


Asunto(s)
Dineínas Axonemales/genética , Bronquiectasia/genética , Síndrome de Kartagener/genética , Bronquiectasia/diagnóstico , Bronquiectasia/patología , Niño , Codón sin Sentido/genética , Codón sin Sentido/aislamiento & purificación , Femenino , Pruebas Genéticas , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Lactante , Síndrome de Kartagener/diagnóstico , Síndrome de Kartagener/patología , Masculino , Mutación Missense/genética , Linaje , Fenotipo
18.
J Microsc ; 263(1): 113-7, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-26854176

RESUMEN

Transmission electron microscopy (TEM) provides sub-nanometre-scale details in volumetric samples. Samples such as pathology tissue specimens are often stained with a metal element to enhance contrast, which makes them opaque to optical microscopes. As a result, it can be a lengthy procedure to find the region of interest inside a sample through sectioning. We describe micro-CT scouting for TEM that allows noninvasive identification of regions of interest within a block sample to guide the sectioning step. In a tissue pathology study, a bench-top micro-CT scanner with 10 µm resolution was used to determine the location of patches of the mucous membrane in osmium-stained human nasal scraping samples. Once the regions of interest were located, the sample block was sectioned to expose that location, followed by ultra-thin sectioning and TEM to inspect the internal structure of the cilia of the membrane epithelial cells with nanometre resolution. This method substantially reduced the time and labour of the search process from typically 20 sections for light microscopy to three sections with no added sample preparation.


Asunto(s)
Microscopía Electrónica de Transmisión/métodos , Microtomografía por Rayos X , Bronquiectasia/patología , Cilios/ultraestructura , Células Epiteliales/patología , Células Epiteliales/ultraestructura , Resinas Epoxi , Humanos , Imagenología Tridimensional , Metales , Microtomía , Mucosa Nasal/patología , Mucosa Nasal/ultraestructura , Factores de Tiempo , Microtomografía por Rayos X/instrumentación
20.
Clin Radiol ; 71(11): 1126-31, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27394062

RESUMEN

AIM: To evaluate the high-resolution computed tomography (CT) findings of primary lung cancer with cavitation and compare the findings in adenocarcinoma and squamous cell carcinoma. MATERIALS AND METHODS: The high-resolution CT findings of tumours with cavitation were retrospectively evaluated in 60 patients. Forty-seven of the lesions were diagnosed as adenocarcinomas; 13 were diagnosed as squamous cell carcinomas. The diameters of the tumour and cavity, the maximum thickness of the cavity wall, shape of the cavity wall, the number of cavities, and the presence of ground-glass opacity, bronchial obstruction, intratumoural bronchiectasis, emphysema, and honeycombing were evaluated. The mechanisms of cavity formation were examined according to the pathological features. RESULTS: The maximum thickness of the cavity wall was significantly greater in squamous cell carcinomas than in adenocarcinomas (p=0.002). Ground-glass opacity and intratumoural bronchiectasis were significantly more common in adenocarcinomas than in squamous cell carcinomas (p<0.001 and p=0.040, respectively). Regarding the pathological findings, intratumoural bronchiectasis with or without alveolar wall destruction contributed to a significant difference between adenocarcinoma and squamous cell carcinoma (p<0.001; odds ratio [OR], 20.35; 95% confidence interval [CI], 3.87-107.10). CONCLUSION: The cavity wall tends to be thicker in squamous cell carcinomas than in adenocarcinomas. The presence of ground-glass opacity and intratumoural bronchiectasis is strongly suggestive of adenocarcinoma.


Asunto(s)
Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/patología , Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/patología , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Tomografía Computarizada por Rayos X/métodos , Anciano , Anciano de 80 o más Años , Bronquiectasia/diagnóstico por imagen , Bronquiectasia/patología , Femenino , Humanos , Pulmón/diagnóstico por imagen , Pulmón/patología , Masculino , Persona de Mediana Edad , Necrosis , Estudios Retrospectivos
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