RESUMEN
OBJECTIVE: To investigate the related risk factors for bronchiolitis obliterans (BO) in children with mycoplasma pneumonia (MP) bronchiolitis. METHOD: The clinical data of 227 children with MP bronchiolitis who were admitted to the II Department of Respiratory of Children's Hospital of Hebei Province from January 2018 to June 2020 were retrospectively analyzed. According to the sequelae of BO, they were divided into 32 cases in the BO group and 195 cases in the non-BO group. The univariate analysis was performed on the clinical and laboratory parameters of the two groups, and the multifactor logistic regression was performed further to determine the independent risk factors for the occurrence of BO in MP bronchiolitis, and then, the cut-off value with the maximum diagnostic value of indicators was found through the ROC curve analysis. RESULTS: The results of univariate and multivariate logistic regression analysis showed that the independent risk factors for the occurrence of BO in MP bronchioles were longer duration of moist rales (OR = 1.203, P = 0.003), higher levels of serum lactate dehydrogenase (LDH) (OR = 1.005, P = 0.036), hypoxemia (OR = 7.442, P = 0.035), and pleural effusion (OR = 4.437, P = 0.004). The area under the ROC curve was 78.2%, 72.0%, 68.2%, and 71.0%, respectively (P < 0.001). The cut-off value of duration of moist rales and levels of serum LDH are 7.5 d and 330 U/L, respectively. CONCLUSION: Children with MP bronchiolitis with high serum LDH level (≥330 U/L), combined with hypoxemia, pleural effusion, and lung wet rale duration (≥7.5 d), may be more prone to BO, in which lung wet rale duration prediction value is the largest. Among them, duration of pulmonary moist rales has the highest predictive value.
Asunto(s)
Bronquiolitis Obliterante/etiología , Bronquiolitis/complicaciones , Neumonía por Mycoplasma/complicaciones , Adolescente , Bronquiolitis/enzimología , Bronquiolitis/microbiología , Bronquiolitis Obliterante/enzimología , Bronquiolitis Obliterante/microbiología , Niño , Preescolar , Biología Computacional , Femenino , Humanos , Hipoxia/complicaciones , Lactante , L-Lactato Deshidrogenasa/sangre , Modelos Logísticos , Masculino , Análisis Multivariante , Mycoplasma pneumoniae , Derrame Pleural/complicaciones , Neumonía por Mycoplasma/enzimología , Curva ROC , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Acid sphingomyelinase (ASM) is a lysosomal enzyme that hydrolyzes sphingomyelin into ceramide, a bioactive lipid to regulate cellular physiological functions. Thus, ASM activation has been reported as a key event in pathophysiological reactions including inflammation, cytokine release, oxidative stress, and endothelial damage in human diseases. Since ASM activation is associated with extracellular ASM secretion through unknown mechanisms, it can be detected by recognizing the elevation of secretory ASM (S-ASM) activity. Serum S-ASM activity has been reported to increase in chronic diseases, acute cardiac diseases, and systemic inflammatory diseases. However, the serum S-ASM has not been investigated in common acute illness. This study was designed to evaluate serum S-ASM activity in children with common acute illness. Fifty children with common acute illness and five healthy children were included in this study. The patients were categorized into five groups based on clinical diagnoses: acute respiratory syncytial virus (RSV) bronchiolitis, adenovirus infection, streptococcal infection, asthma, and other infections due to unknown origin. The serum S-ASM activity was significantly elevated at 6.9 ± 1.6 nmol/0.1 mL/6 h in the group of acute RSV bronchiolitis patients compared with healthy children who had a mean level of 1.8 ± 0.8 nmol/0.1 mL/6 h (p < 0.05). In the other illness groups, the serum S-ASM activity was not significantly elevated. The results suggest an association of ASM activation with RSV infection, a cause for common acute illness. This is the first report to describe the elevation of serum S-ASM activity in respiratory tract infection.
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Bronquiolitis/sangre , Bronquiolitis/enzimología , Infecciones por Virus Sincitial Respiratorio/sangre , Infecciones por Virus Sincitial Respiratorio/enzimología , Esfingomielina Fosfodiesterasa/sangre , Enfermedad Aguda , Adolescente , Bronquiolitis/diagnóstico , Niño , Preescolar , Demografía , Femenino , Humanos , Concentración de Iones de Hidrógeno , Lactante , Interleucina-6/sangre , Masculino , Infecciones por Virus Sincitial Respiratorio/diagnósticoRESUMEN
The mechanism by which severe bronchiolitis can result in the development of recurrent childhood wheeze is unclear. However, mucosal inflammation and immune activation may play a major role. Prostaglandin (PG) E(2) has been highlighted as a possible therapeutic target for both the treatment of bronchiolitis and the prevention of subsequent airway hyperresponsiveness. The aim of this pilot study was to examine PGE(2) in the airways of infants hospitalised with bronchiolitis. Nasopharyngeal aspirates (NPA) were collected from 18 infants within 12 hours of admission and assayed by enzyme immunoassays for PGE(2), interleukin (IL)-10, and IL-12, as well as cyclooxygenase (COX) 1 and 2 activity. NPA PGE(2) concentration correlated with length of illness preadmission, but was not related to disease severity, causal virus, or IL-10. NPA COX 1 and 2 activity and IL-12 were all below the level of detection. Neither NPA PGE(2) nor disease severity was related to development of recurrent wheeze over 3 years following bronchiolitis. These data suggest that nasopharygeal PGE(2) at hospital admission may be neither directly causal or diagnostic of severity of infant bronchiolitis, or prognostic of development of recurrent wheeze. However, large-cohort temporal examinations are required to adequately define this mediator as a therapeutic target for bronchiolitis.
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Bronquiolitis/metabolismo , Dinoprostona/metabolismo , Nasofaringe/metabolismo , Bronquiolitis/enzimología , Ciclooxigenasa 1/metabolismo , Ciclooxigenasa 2/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Lactante , Interleucina-10/metabolismo , Interleucina-12/metabolismo , Masculino , Proyectos PilotoRESUMEN
Objectives: We characterised the T helper cytokine profiles on the surface of nasal mucosa of children with acute bronchiolitis caused by Respiratory Syncytial Virus, Parainfluenza Virus, Influenza Virus, Adenovirus, or without any viral identification, in order to examine whether these viral types modified cytokine responses. As an additional objective we sought to determine if T helper polarisation was associated with other demographic and environmental factors. Methods: A prospective study of children with acute bronchiolitis was performed. Patients were recruited from the emergency department of a central hospital in Lisbon, Portugal. Demographical, epidemiological and clinical data were gathered from a questionnaire. Nasal swabs were collected for viral studies (immunofluorescence) and T cell cytokine responses (detection of expression of interleukins 4, 13, 12 and interferon-ã by real-time polymerase chain reaction assays). Results: Respiratory Syncytial Virus elicited lower levels of interleukin 4, when compared with samples without virus identification. A similar tendency to Th1 polarisation was found in older children, in those who attended day-care centres, and in breastfed individuals. Exposure to tobacco smoke was associated with a Th2 bias in this population.ConclusionsThese findings show that Respiratory Syncytial Virus infection contributes to Th1 polarisation in immune response of respiratory mucosa, an effect that is similar to other environmental factors. Further studies are needed to assess immune response to other infectious causes of acute bronchiolitis (AU)
Asunto(s)
Humanos , Masculino , Femenino , Preescolar , Bronquiolitis/diagnóstico , Bronquiolitis/enzimología , Secreciones Corporales/enzimología , Interleucina-12/análisis , Interleucina-12 , Interleucina-4/análisis , Citocinas/análisis , Citocinas , Receptores de Citocinas/biosíntesis , Encuestas y Cuestionarios , 28599RESUMEN
The impact of smoking on the peripheral airways, the determining field of respiratory functions in the lungs, is well known. Fifty two cases were included in the study; autopsy cases of non-cardiopulmonary related deaths with a smoking history, and cases with lung resection, known as smokers. Ten cases without a smoking history and a systemic disease were used as a control group at the histopathological examination. Parenchymal samples were taken from the central and peripheral airways (1st, 2nd, 3rd division) and from each lob. In addition, age, gender, amount and duration of smoking (package/year) were considered and histopathological changes of the lung are evaluated under the light microscope. The relations of all parameters to each other are evaluated and compared with the control group. On the distal airways with small diameter, Respiratory Bronchiolitis (RB) was determined in 14 (26.9%) cases, and Respiratory Bronchiolitis-associated interstitial lung disease (RB-ILD) in 16 (30.7%) cases. Two (3.8%) cases were diagnosed as Desquamative Interstitial Pneumonia (DIP). MMP-9, a matrix metalloproteinase known for its role in the development and repair of obstructive diseases of the lung related to smoking, and TIMP-1, an inhibitor, were used on the lung samples by means of immunohistochemical method. MMP-9 and TIMP-1 expressions of all cases were compared statistically with the existing pathological findings and the control group. MMP-9, TIMP-1 were expressed from the alveolar macrophages, endothelial and epithelial cells. Considering the MMP-9 and TIMP-1 density of alveolar macrophages, no statistically significant differences were found among the RB, RBILD and DIP case groups. However; despite of the significant MMP-9 expression of the DIP cases, TIMP-1 expression could not be determined. Compared to the control group, a more intensive and widespread positive reaction on MMP-9 was found in the alveolar macrophages. In conclusion, although there was no significant relation between the level and duration of smoking and the MMP-9 and TIMP-1 expressions, alveolar macrophages were found to be more important in lung damage related to smoking and the MMP-9 expression from these cells to be more intensive than the control group.
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Pulmón/patología , Metaloproteinasa 9 de la Matriz/análisis , Fumar/efectos adversos , Inhibidor Tisular de Metaloproteinasa-1/análisis , Adulto , Anciano , Bronquiolitis/enzimología , Bronquiolitis/patología , Estudios de Casos y Controles , Femenino , Humanos , Inmunohistoquímica , Pulmón/enzimología , Pulmón/ultraestructura , Enfermedades Pulmonares Intersticiales/enzimología , Enfermedades Pulmonares Intersticiales/patología , Masculino , Persona de Mediana EdadRESUMEN
Idiopathic usual interstitial pneumonia/idiopathic pulmonary fibrosis (UIP/IPF) and asbestosis represent progressive and often fatal pulmonary fibrous disorders, whereas cryptogenic organizing pneumonia (COP), desquamative interstitial pneumonia (DIP), and respiratory bronchiolitis-interstitial lung disease (RB-ILD) usually are reversible or nonprogressive conditions. Prostaglandin E2 (PGE2) inhibits fibroblast proliferation and myofibroblast transition, its production depending on cyclooxygenase-2 (COX-2). In patients with UIP/IPF, levels of PGE2 and COX-2 are reduced in fibroblasts, and levels of PGE2 in bronchioalveolar lavage fluid may be lowered. We analyzed the immunohistochemical expression of COX-2 in UIP/IPF, asbestosis, COP, DIP, and RB-ILD. Our results show that the metaplastic epithelium in UIP/IPF, asbestosis, and COP is widely COX-2+, whereas COX-2 positivity is scant in DIP and RB-ILD. The mesenchymal cells remained negative. Our results suggest that irrespective of the underlying disease, lung injury that causes extensive fibrosis induces wide expression of COX-2 in the regenerating metaplastic epithelium.
Asunto(s)
Ciclooxigenasa 2/metabolismo , Proteínas de la Membrana/metabolismo , Fibrosis Pulmonar/patología , Asbestosis/enzimología , Asbestosis/patología , Bronquiolitis/enzimología , Bronquiolitis/patología , Neumonía en Organización Criptogénica/enzimología , Neumonía en Organización Criptogénica/patología , Epitelio/enzimología , Epitelio/patología , Humanos , Inmunohistoquímica , Enfermedades Pulmonares Intersticiales/enzimología , Enfermedades Pulmonares Intersticiales/patología , Metaplasia , Fibrosis Pulmonar/enzimologíaRESUMEN
Pseudomonas aeruginosa frequently colonizes the respiratory tract of patients suffering from cystic fibrosis (CF) and diffuse panbronchiolitis (DPB). However, the relationship between lung inflammation and extracellular products of P. aeruginosa is not well-defined. To assess the role of elastase released by P. aeruginosa in DPB, a murine model of DPB was employed in this study. Mice were inoculated with either P. aeruginosa PAO1 or PAO-E64; the latter produces elastase with greatly reduced enzymic activity. Throughout the 90-day experiments, counts of viable bacteria from the PAO1- and PAO-E64-infected mice were found to be equivalent. However, the number of lymphocytes isolated from the lungs of PAO-E64-infected mice was significantly lower than the number isolated from the lungs of PAO1-infected animals. Histopathological examination of the lungs of mice infected by PAO1 on day 90 revealed an intense accumulation of chronic respiratory cells surrounding the bronchi, in sharp contrast to the more localized inflammatory response found in those mice infected by PAO-E64. These data suggest that P. aeruginosa elastase (PE) is a potent inflammatory factor in a mouse model of DPB and that the control of PE release by P. aeruginosa may be beneficial for patients with DPB.
Asunto(s)
Bronquiolitis/enzimología , Fibrosis Quística/complicaciones , Elastasa Pancreática/fisiología , Infecciones por Pseudomonas/enzimología , Pseudomonas aeruginosa/enzimología , Animales , Bronquiolitis/microbiología , Bronquiolitis/patología , Enfermedad Crónica , Recuento de Colonia Microbiana , Modelos Animales de Enfermedad , Pulmón/microbiología , Pulmón/patología , Recuento de Linfocitos , Masculino , Ratones , Infecciones por Pseudomonas/microbiología , Infecciones por Pseudomonas/patología , Pseudomonas aeruginosa/crecimiento & desarrollo , Organismos Libres de Patógenos EspecíficosRESUMEN
BACKGROUND: Diffuse panbronchiolitis (DPB) is characterized by chronic neutrophil-mediated inflammation of the airway mediated by oxygen radical production. DPB can be controlled with low-dose and long-term erythromycin therapy based on its anti-inflammatory effect. OBJECTIVE: In this study, the antioxidant levels were analyzed as an anti-inflammatory effect of erythromycin in the patients. METHODS: We investigated the activity and protein level of an antioxidant enzyme, Cu, Zn-superoxide dismutase (SOD) in alveolar macrophages (AMs) of patients with DPB before and after erythromycin therapy. AMs were obtained from bronchoalveolar lavage fluid. RESULTS: There was no significant difference in the activity of Cu, Zn-SOD between normal subjects and untreated patients. Erythromycin therapy (600 mg/day) significantly increased the activity of the enzyme relative to that before therapy and normal subjects [18.2 units/10(6) cells (9.2-26.2) vs. 4.4 units/10(6) cells (1.1-9.3), p < 0.01 and 10.4 units/10(6) cells (2.4-20.6), p < 0.05, respectively]. Furthermore, the protein level of Cu, Zn-SOD in AMs in treated patients was significantly higher than in the other two groups [69.4 ng/10(6) cells (34.2-147.1) vs. 20.1 ng/ 10(6) cells (16.9-39.8) for untreated patients, p < 0.01 and 43.2 ng/10(6) cells (32.6-68.2) for normal subjects, p < 0.01], but the levels in the latter groups were not different. CONCLUSION: Our results suggest that one of the anti-inflammatory effects of erythromycin in DPB may be, in part, mediated by enhancement of antioxidant activity in AMs.
Asunto(s)
Bronquiolitis/tratamiento farmacológico , Eritromicina/uso terapéutico , Macrófagos Alveolares/enzimología , Superóxido Dismutasa/metabolismo , Adulto , Anciano , Bronquiolitis/enzimología , Líquido del Lavado Bronquioalveolar/citología , Estudios de Casos y Controles , Recuento de Células , Eritromicina/farmacología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neutrófilos , Distribución Aleatoria , Valores de ReferenciaRESUMEN
BACKGROUND: There are some reports of the coexistence of chronic suppurative lung diseases such as cystic fibrosis and systemic vasculitis. Diffuse panbronchiolitis has the same characteristics as chronic recurrent sinopulmonary infection and respiratory bronchiolitis. METHODS: Serum samples from 30 patients with diffuse panbronchiolitis and 57 patients with other pulmonary diseases were tested to find the titer of myeloperoxidase antineutrophil cytoplasmic antibodies (MPO-ANCA). RESULTS: We found MPO-ANCA positivity in 4 patients with diffuse panbronchiolitis but not in those with other pulmonary diseases. CONCLUSIONS: Our findings show that MPO-ANCA is positive in some patients with diffuse panbronchiolitis. Careful attention should be paid to the combination of chronic pulmonary infection and various vasculitis.
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Anticuerpos Anticitoplasma de Neutrófilos/análisis , Bronquiolitis/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Bronquiolitis/enzimología , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Enfermedades Pulmonares/enzimología , Enfermedades Pulmonares/inmunología , Masculino , Persona de Mediana Edad , Peroxidasa/análisisRESUMEN
Epidemiologic studies suggest an association between recurrent bronchiolitis in children younger than 3 years of age and diagnosis of asthma later in life. Bronchoalveolar lavages from 20 infants with recurrent wheezing and 18 nonwheezy control subjects were analyzed to determine whether alveolar macrophages of wheezy infants present abnormalities similar to those described in adults with asthma. Alveolar macrophages from both groups responded in vitro, in a concentration-dependent manner, to prostaglandin E2, salbutamol, and forskolin, drugs that increase cyclic adenosine monophosphate levels. However, alveolar macrophages from infants with recurrent wheezing accumulated less cyclic adenosine monophosphate than those from control subjects in response to all three stimulations. These results are in agreement with the reduced cyclic adenosine monophosphate response to different agonists demonstrated in leukocytes from patients with asthma, and suggest that this refractoriness could be one of the precipitating events in the development of asthma observed in a large proportion of infants who have had bronchiolitis.
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Adenilil Ciclasas/metabolismo , Bronquiolitis/enzimología , Macrófagos Alveolares/enzimología , Adenilil Ciclasas/efectos de los fármacos , Albuterol/farmacología , Asma/etiología , Bronquiolitis/complicaciones , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Broncoscopía , Colforsina/farmacología , AMP Cíclico/análisis , Dinoprostona/farmacología , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Lactante , Macrófagos Alveolares/química , Macrófagos Alveolares/efectos de los fármacos , Masculino , Recurrencia , Ruidos Respiratorios/fisiopatología , Estimulación QuímicaRESUMEN
The authors have tried to value in 17 children (age: 1-11 months) affected by a severe acute viral bronchiolitis, if the measurement of Lactate Dehydrogenase (LD) isoenzymes could have been used to reveal alveolar injury. In the 76.4% (13/17) of subjects areas of consolidation were demonstrated by chest's radiographic examination due either to atelectasis secondary to obstruction or to inflammation of the alveoli. These coincided with a significant increase respect to a check's group (18 children) of LD4 in 70.5% (12/17), LD3 in 35.2% (6/17) and LD5 in 29.4% (5/17) of children. The presence of an analogous electrophoretic pattern and macrophages degenerated in pulmonary alveolar proteinosis lavage effluent associated with increases in lymphocytes and mononuclear phagocytes in lung specimens from children dead for bronchiolitis help to understand the inflammatory origin of pathological modification of LD isoenzymes observed in this series of cases.
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Bronquiolitis/enzimología , L-Lactato Deshidrogenasa/sangre , Alveolos Pulmonares/enzimología , Enfermedad Aguda , Bronquiolitis/complicaciones , Femenino , Humanos , Lactante , Inflamación/enzimología , Inflamación/etiología , Isoenzimas , MasculinoRESUMEN
Diffuse panbronchiolitis (DPB) is a disease of adults characterized by chronic inflammation of the respiratory bronchioles and the infiltration of chronic inflammatory cells. The clinical efficacy of erythromycin therapy has been demonstrated in DPB patients, but the mechanism of action of this drug is unknown. We investigated the localization of neutrophils in lung biopsy specimens, as well as the cell population and elastolytic-like and chemotactic activity of bronchoalveolar lavage (BAL) fluid, before and after treatment with erythromycin or ampicillin in 11 DPB patients (six biopsy-proven and five clinically diagnosed) and one follicular bronchiolitis patient. These bronchiolitis patients had a high percentage of neutrophil and a high neutrophil-derived elastolytic-like activity in BAL fluid compared with chronic bronchitis patients and normal control subjects. The number of neutrophils and the neutrophil-derived elastolytic-like activity in BAL fluid decreased significantly after treatment with erythromycin along with a significant improvement in pulmonary function studies, although there was no significant change in the chemotactic activity of BAL fluid. No significant reduction in BAL fluid neutrophilia was found in the ampicillin-treated patients. These results suggest an important role for the neutrophil in the pathogenesis or development of bronchiolitis, and also suggest that erythromycin may be useful for the treatment of bronchiolitis through its direct action upon host phagocytic cells.
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Bronquiolitis/patología , Eritromicina/farmacología , Pulmón/patología , Neutrófilos/efectos de los fármacos , Elastasa Pancreática/metabolismo , Adolescente , Adulto , Ampicilina/farmacología , Bronquios/patología , Bronquiolitis/enzimología , Bronquiolitis/fisiopatología , Líquido del Lavado Bronquioalveolar/enzimología , Líquido del Lavado Bronquioalveolar/patología , Quimiotaxis de Leucocito/efectos de los fármacos , Femenino , Humanos , Elastasa de Leucocito , Masculino , Persona de Mediana Edad , Neutrófilos/patología , Neutrófilos/fisiología , Mecánica RespiratoriaRESUMEN
To examine the mechanism of tissue damage which causes bronchiolectasis in diffuse panbronchiolitis (DPB), the cellular components, elastase and its main inhibitor, alpha 1-protease inhibitor (alpha 1-PI) were measured in bronchoalveolar and bronchial lavage fluid (BALF and BLF) from 14 DPB patients. A predominant increase in the neutrophil count was observed in DPB. Elastase activity in BALF and BLF was about 1,000-fold higher in the DPB group than in the control group. An inhibitor study and a positive correlation between elastase activity and the neutrophil count in both lavage fluids from the DPB group indicated that the activity was mainly that of neutrophil elastase. Western blot analysis of alpha 1-PI showed that most of the alpha 1-PI in the lavage fluids from DPB group was degraded. These results indicated that neutrophil infiltration increases the level of elastase in the DPB lesions; this increase seems to be closely related to tissue damage.
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Bronquiolitis/enzimología , Bronquiolitis/patología , Elastasa Pancreática/metabolismo , Adulto , Anciano , Bronquiolitis/etiología , Líquido del Lavado Bronquioalveolar/metabolismo , Líquido del Lavado Bronquioalveolar/patología , Recuento de Células , Femenino , Humanos , Masculino , Persona de Mediana Edad , Peso Molecular , Neutrófilos/enzimología , Neutrófilos/patología , alfa 1-Antitripsina/aislamiento & purificación , alfa 1-Antitripsina/metabolismoRESUMEN
The clinical and pathological features of diffuse panbronchiolitis (DPB) have been well reported to date though its pathogenesis remains unknown. This study was designed to evaluate the protease antiprotease imbalance in patients with DPB. For this purpose, we performed bronchoalveolar lavage (BAL) in sixteen patients with DPB, twelve patients with chronic bronchitis (CB) and control subjects (nine smokers and eleven non-smokers), and determined elastase activity and alpha 1 antitrypsin (alpha 1 AT) concentration in bronchoalveolar lavage fluid (BALF). Elastase activity was measured using a synthetic substrate, succinyl-tri-L-alanine-p-nitroanilide. BALF from eleven of sixteen patients with DPB showed elastase activity. However, only two of twelve patients with CB showed elastase activity, and control subjects did not show any elastase activity in BALF. Although alpha 1 AT concentration is elevated in BALF from patients with DPB, it is assumed that elastase burden exceeded the elastase inhibitory capacity of alpha 1 AT in BALF. The percentage of neutrophils in BALF correlated significantly with elastase activity which was inhibited by DFP, but not by EDTA. These data revealed that the elastase in BALF was a serine protease of neutrophil origin. In five DPB-patients treated with low-dose long-term erythromycin chemotherapy, elastase activity in BALF decreased significantly. The above mentioned findings suggest that the neutrophil elastase plays an important role in the pathogenesis of DPB, and the mode of action of erythromycin on DPB is to decrease the elastase burden.