RESUMEN
BACKGROUND: The gut-lung axis, pivotal for respiratory health, is inadequately explored in pulmonary and critical care medicine (PCCM) inpatients. METHODS: Examining PCCM inpatients from three medical university-affiliated hospitals, we conducted 16S ribosomal RNA sequencing on stool samples (inpatients, n = 374; healthy controls, n = 105). We conducted statistical analyses to examine the gut microbiota composition in PCCM inpatients, comparing it to that of healthy controls. Additionally, we explored the associations between gut microbiota composition and various clinical factors, including age, white blood cell count, neutrophil count, platelet count, albumin level, hemoglobin level, length of hospital stay, and medical costs. RESULTS: PCCM inpatients exhibited lower gut microbiota diversity than healthy controls. Principal Coordinates Analysis revealed marked overall microbiota structure differences. Four enterotypes, including the exclusive Enterococcaceae enterotype in inpatients, were identified. Although no distinctions were found at the phylum level, 15 bacterial families exhibited varying abundances. Specifically, the inpatient population from PCCM showed a significantly higher abundance of Enterococcaceae, Lactobacillaceae, Erysipelatoclostridiaceae, Clostridiaceae, and Tannerellaceae. Using random forest analyses, we calculated the areas under the receiver operating characteristic curves (AUCs) to be 0.75 (95% CIs 0.69-0.80) for distinguishing healthy individuals from inpatients. The four most abundant genera retained in the classifier were Blautia, Subdoligranulum, Enterococcus, and Klebsiella. CONCLUSIONS: Evidence of gut microbiota dysbiosis in PCCM inpatients underscores the gut-lung axis's significance, promising further avenues in respiratory health research.
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Disbiosis , Microbioma Gastrointestinal , Humanos , Microbioma Gastrointestinal/fisiología , Masculino , Disbiosis/diagnóstico , Femenino , Persona de Mediana Edad , Anciano , Cuidados Críticos , Pacientes Internos , Adulto , Heces/microbiologíaRESUMEN
Bronchiectasis is a complex and heterogeneous disease with a myriad of pulmonary and extrapulmonary etiologies. Bronchiectasis has a predominantly neutrophilic inflammatory profile. However, eosinophilic inflammation has also been documented in both the airways and the systemic circulation. Various diseases (eg, asthma, allergic bronchopulmonary aspergillosis, chronic rhinosinusitis with nasal polyps) characterized by heightened type 2 airway inflammatory responses, including blood or sputum eosinophilia, may coexist with bronchiectasis. Apart from those eosinophilic etiologies or comorbidities related to bronchiectasis, around 20% of patients with bronchiectasis have peripheral eosinophilia (at least 3% or 300 eosinophils/µL) with no identified concomitant disease (also termed "eosinophilic bronchiectasis"), whose roles have not been fully understood. The two key points regarding these observations are that eosinophils confer both bactericidal and antiviral properties against common pathogenic microorganisms that are usually detected in bronchiectasis, and that eosinophilic bronchiectasis has been associated with better therapeutic response to inhaled corticosteroids and other anti-TH2 profile treatments. In this review, we summarize the most significant evidence regarding the role of eosinophils in patients with bronchiectasis, including the association of bronchiectasis with eosinophilic diseases (as etiologies or comorbidities), and existing data on eosinophilic bronchiectasis not related to eosinophilic disorders.
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Bronquiectasia , Eosinofilia , Humanos , Eosinófilos/patología , Pulmón/patología , Eosinofilia/patología , FibrosisRESUMEN
Human adenoviruses type 26 (HAdV26) and type 35 (HAdV35) have increasingly become the choice of adenovirus vectors for vaccine application. However, the population pre-existing immunity to these two adenoviruses in China, which may reduce vaccine efficacy, remains largely unknown. Here, we established micro-neutralizing (MN) assays to investigate the seroprevalence of neutralizing antibodies (nAbs) against HAdV26 and HAdV35 in the general population of Guangdong and Shandong provinces, China. A total of 1184 serum samples were collected, 47.0% and 15.8% of which showed HAdV26 and HAdV35 nAb activity, respectively. HAdV26-seropositive individuals tended to have more moderate nAbs titers (201-1000), while HAdV35-seropositive individuals appeared to have more low nAbs titers (72-200). The seropositive rates of HAdV26 and HAdV35 in individuals younger than 20 years old were very low. The seropositive rates of HAdV26 increased with age before 70 years old and decreased thereafter, while HAdV35 seropositive rates did not show similar characteristics. Notably, the seropositive rates and nAb levels of both HAdV26 and HAdV35 were higher in Guangdong Province than in Shandong Province, but did not exert significant differences between males and females. The seroprevalence between HAdV26 and HAdV35 showed little correlation, and no significant cross-neutralizing activity was detected. These results clarified the characteristics of the herd immunity against HAdV26 and HAdV35, and provided information for the rational development and application of HAdV26 and HAdV35 as vaccine vectors in China.
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Adenovirus Humanos , Anticuerpos Neutralizantes , Adenoviridae , Adulto , Anciano , Anticuerpos Antivirales , China/epidemiología , Femenino , Humanos , Masculino , Estudios Seroepidemiológicos , Adulto JovenRESUMEN
Unlike the pulmonary artery (PA), the pathophysiological changes of the pulmonary vein (PV) in the development of pulmonary hypertension (PH) remain largely unknown. In this study, we comprehensively investigated the structural and functional changes in the PV isolated from the chronic hypoxia (CH; 10% O2, 21 days)-induced PH rat model (CHPH). Results showed that CH caused an increase in right ventricular pressure but did not affect the mean pulmonary venous pressure and the left atrial pressure. Similar to the PA, vascular lumen stenosis and medial thickening were also observed in the intrapulmonary veins isolated from the CHPH rats. Notably, CH induced more severe loss in the endothelium of intrapulmonary veins than the arteries. Then, the contractile response to 5-HT and U46619 was significantly greater in the intrapulmonary small veins (ISPV) and arteries (ISPA) isolated from CHPH rats than those from normoxic rats but not in the extrapulmonary and intrapulmonary large veins. Treatment with nifedipine (Nif), SKF96365 (SKF), or ryanodine and caffeine either partially attenuated (Nif) or dramatically abolished (SKF or ryanodine and caffeine) 5-HT-induced maximal contraction in ISPV from both normoxic and CHPH rats. Because of the severe loss of endothelium in the PV of CHPH rats, the decrease in acetylcholine (ACh)-induced endothelium-dependent relaxation was significantly larger in ISPV than ISPA, whereas the sodium nitroprusside-induced endothelium-independent relaxation was not altered in both ISPA and ISPV. In conclusion, our results provide fundamental data to comprehensively define the PV system in CHPH rat model.
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Modelos Animales de Enfermedad , Hipertensión Pulmonar/fisiopatología , Hipoxia/fisiopatología , Venas Pulmonares/citología , Venas Pulmonares/fisiología , Animales , Células Cultivadas , Enfermedad Crónica , Hipertensión Pulmonar/inducido químicamente , Hipertensión Pulmonar/patología , Hipoxia/patología , Masculino , Técnicas de Cultivo de Órganos , Venas Pulmonares/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Vasoconstrictores/toxicidad , Vasodilatadores/farmacologíaRESUMEN
BACKGROUND: Asthma is a heterogeneous disease with diverse clinical manifestations and inflammatory pathologies that is punctuated by exacerbations. OBJECTIVE: To describe the clinical and inflammatory characteristics of patients with asthma treated in hospital for an acute exacerbation. METHODS: Data from 320 adult patients receiving treatment for an acute exacerbation of asthma were obtained. In 218 patients with complete data, we used the Ward hierarchical clustering to obtain clusters. Pulmonary function, blood cell counts, sputum cell counts, serum IgE levels, and fractional exhaled nitric oxide were measured on hospital admission. We selected 13 variables with which we performed the Ward minimum-variance hierarchical clustering. RESULTS: Four clusters were defined. Clusters 1 (24.5%) and 3 (36.7%) were characterized by predominantly female patients with asthma with sputum neutrophilia, with cluster 1 associated with a small degree of airflow obstruction and early-onset asthma and cluster 3 with a moderate degree of reduction in FEV1. Clusters 2 (22.0%) and 4 (16.5%) were associated with high sputum eosinophilia and severe airflow obstruction. Cluster 4 was made exclusively of male smoking subjects, whereas cluster 2 was made up of predominantly female nonsmoking subjects with the worst FEV1, forced expiratory flow at 25% to 75% of forced vital capacity (% predicted), and partial pressure of oxygen in arterial blood on admission. There were no differences between clusters in terms of atopy, serum IgE, prevalence of nasal disease, dose of maintenance inhaled corticosteroids, or oral/systemic corticosteroid use and asthma exacerbations. CONCLUSIONS: The clusters during recovery from an exacerbation of asthma were distinguished by airflow obstruction and a neutrophilic, eosinophilic, or mixed inflammation. Eosinophilic inflammation was found in smoking and nonsmoking patients with asthma during an exacerbation.
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Asma , Corticoesteroides/uso terapéutico , Adulto , Asma/tratamiento farmacológico , Asma/inmunología , Asma/metabolismo , Asma/fisiopatología , Progresión de la Enfermedad , Eosinofilia/tratamiento farmacológico , Eosinofilia/inmunología , Eosinofilia/metabolismo , Eosinofilia/fisiopatología , Femenino , Volumen Espiratorio Forzado , Hospitalización , Humanos , Inmunoglobulina E/sangre , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Óxido Nítrico/metabolismo , Fenotipo , Fumar/tratamiento farmacológico , Fumar/inmunología , Fumar/metabolismo , Fumar/fisiopatología , Capacidad VitalRESUMEN
OBJECTIVE: To relieve large airway obstruction in a patient with advanced non-small cell lung cancer (NSCLC) by injecting the mouse-human chimeric monoclonal antibody radiolabeled with iodine 131 chimeric tumor necrotic treatment (131I-chTNT) and to study the irradiation absorption in the tumor and critical organs. METHODS: A 50-year-old patient with NSCLC was treated with radioimmunotherapy. His airway was still obstructed in spite of intensive chemotherapy and radiotherapy.131I-chTNT was injected into the tumor at the right bronchus through a fiberscope. A131I scan was performed during treatment, and a computed tomography (CT) scan of the chest and fiberscope were performed pre- and post-treatment.131I-chTNT distribution in tissues was followed for up to 4 weeks using gamma camera imaging. RESULTS: The radiation material accumulated notably in the tumor, relieving the patient's symptoms by suppressing the tumor. Recanalization of the airway was achieved so that the patient was able to breathe easily and cough. CONCLUSION: As a new type of radioimmunotherapy,131I-chTNT may be helpful in treatment of advanced lung cancer.
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Obstrucción de las Vías Aéreas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Radioinmunoterapia , Tráquea/fisiopatología , Factor de Necrosis Tumoral alfa/uso terapéutico , Anticuerpos Monoclonales , Humanos , Inyecciones , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
OBJECTIVE: To investigate the effects of budesonide (BUD) on the airway remodeling and the expression of Janus protein tyrosine kinases 1 (JAK1) and signal transducer and activator of transcription 6 (STAT6) in asthma. METHODS: Thirty female Balb/c mice were randomly divided into 3 equal groups: control group; asthma group, sensitized on day 1, 8, and 15 and challenged from day 21 to 52 with periodically repeated intranasal drip of ovalbumin (OVA); and BUD treated group, undergoing intranasal drip of OVA as mentioned above and intranasal administration of BUD 2 hours before each OVA challenge. 24 h after the final OVA inhalation an invasive single-chamber whole body plethysmograph was used to assess the airway responsiveness. Then bronchoalveolar lavage fluid (BALF) was obtained and ELISA was used to measure the contents of interleukin (IL)-4 and IL-13. The mice were killed and their lungs taken out. HE staining and periodic acid Schiff (PAS) staining were used to observe the airway score of goblet cells. Peribronchiolar collagen deposition was imaged in Masson-stained lung sections. Biochemical assay was used to determine the total lung tissue level of collagen. Potass hydrolyse method was used to examine the content of hydroxyproline in the lung tissue. Western blotting was used to detect the protein expression of alpha-smooth muscle actin (SMA), JAK1, and STAT6. RT-PCR was used to detect the mRNA expression of alpha-SMA. RESULTS: The value of LogPC100 of the asthma group was 1.88 +/- 0.34, significantly higher than those of the BUD and control groups (1.79 +/- 0.18 and 0.82 +/- 0.78 respectively, both P = 0.000). The airway score of goblet cells of the asthma group was 3.05 +/- 0.23, significantly higher than those of the BUD and control groups (1.35 +/- 0.26 and 0.40 +/- 0.13 respectively, both P < 0.01). The hydroxyproline content of the asthma group was (459 +/- 47) microg/100 mg tissue, significantly higher than those of the BUD and control groups [(284 +/- 16) and (181 +/- 22) microg/100 mg tissue respectively, both P < 0.01]. The level of IL-4 of the asthma group was (14.4 +/- 1.12) ng/L, significantly higher than those of the BUD and control groups [(7.3 +/- 0.6) and (5.6 +/- 0.8) ng/L respectively, both P < 0.01]. The IL-13 level of the asthma group was (16.8 +/- 0.9) ng/L, significantly higher than those of the BUD and control groups [(10.6 +/- 0.9) and (5.6 +/- 0.8) ng/L respectively, both P < 0.01]. Treatment of BUD attenuated the allergen-induced airway hyperresponsiveness (AHR) and structural changes in airway, and decreased the values of the airway scores of goblet cells, and levels of hydroxyproline, IL-4, and IL-13 in comparison with the asthma group (all P < 0.01). Repeated OVA challenge resulted in an upregulation of the expression levels of alpha-SMA, JAK1 and STAT6 protein and alpha-SMA mRNA, while use of BUD suppressed these changes. The changes of JAK1 and STAT6 expression were correlated significantly with the changes in the airway score of goblet cells, hydroxyproline content, expression level of alpha-SMA, and levels of IL-4 and IL-13 in BALF (all P < 0.05). CONCLUSION: BUD ameliorates the progression of airway remodeling following prolonged allergen challenge via regulation of JAK1/STAT6 signal pathway.
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Asma/prevención & control , Budesonida/farmacología , Janus Quinasa 1/biosíntesis , Pulmón/efectos de los fármacos , Factor de Transcripción STAT6/biosíntesis , Actinas/genética , Actinas/metabolismo , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Asma/metabolismo , Asma/fisiopatología , Western Blotting , Budesonida/uso terapéutico , Modelos Animales de Enfermedad , Femenino , Interleucina-13/análisis , Interleucina-4/análisis , Pulmón/metabolismo , Pulmón/fisiopatología , Ratones , Ratones Endogámicos BALB C , Músculo Liso/química , Distribución Aleatoria , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
OBJECTIVE: The spectrum and frequency of causes and the diagnostic protocol for chronic cough were explored. METHODS: A total of 194 patients with at least 3 weeks of chronic cough and normal chest radiographs were recruited from the outpatient clinic of Guangzhou Institute of Respiratory Diseases between July 2003 to June 2004. The causes were investigated using a well-established protocol. The diagnostic protocol included history inquiring and physical examination, pulmonary function tests, induced sputum cell differentials, 24 h esophageal pH monitoring, CT of the paranasal sinuses or chest, fiberoptic rhinoscopy or bronchoscopy. The final diagnosis was made based on clinical manifestation, examination findings and a positive response to therapy. RESULTS: The cause of chronic cough was defined in 95.4% of the patients, with a single cause found in 153 patients (82.7%), and multiple causes in 32 patients (17.3%). The five most important causes of cough were: eosinophilic bronchitis (n = 51, 22.4%), rhinitis and/or paranasal sinusitis (PNDs, n = 39, 17.1%), cough-variant asthma (n = 31, 13.6%), atopic cough (n = 28, 12.3%), and gastroesophageal reflux (n = 27, 11.8%). CONCLUSIONS: The spectrum and frequency of causes of chronic cough in our study is different from the previous reports in western countries. Eosinophilic bronchitis and atopic cough are important causes of chronic cough. A modified diagnostic protocol was established accordingly.
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Tos/diagnóstico , Tos/etiología , Adolescente , Adulto , Anciano , Asma/complicaciones , Enfermedad Crónica , Femenino , Reflujo Gastroesofágico/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Pruebas de Función Respiratoria , Rinitis/complicaciones , Adulto JovenRESUMEN
OBJECTIVE: To investigate the features of airway inflammation in patients with eosinophilic bronchitis (EB) by analyzing the inflammatory cells and mediators in induced sputum and bronchoalveolar lavage fluid (BALF). METHODS: Sputum induced by hypertonic saline aerosol inhalation was collected in 43 patients with EB (EB group), 20 patients with cough variant asthma (CVA, CVA group), 16 patients with bronchial asthma (asthma group) and 21 healthy controls (healthy group). Bronchoalveolar lavage was also performed in 11 patients with EB and 10 patients with CVA. Differential cell count was carried out in sputum and BALF. Levels of eosinophilic cationic protein (ECP), leukotriene C(4) (LTC(4)) and histamine in sputum and BALF were measured. RESULTS: The percentage of sputum eosinophils (EOS) showed significant difference among the four groups; healthy group 0.0020 +/- 0.0050, EB group 0.1130 +/- 0.1470, CVA group 0.1900 +/- 0.1800, asthma group 0.3860 +/- 0.2670 (P < 0.01). The difference between asthma group and CVA group, and the difference between CVA group and EB group were significant (P < 0.05). The percentage of EOS in BALF was (0.011 +/- 0.016) in EB group, (0.053 +/- 0.040) in CVA group, the difference being significant (P < 0.05). The concentration of sputum ECP was (0.62 +/- 0.66) mg/L in EB group, (1.27 +/- 1.74) mg/L in CVA group, (0.07 +/- 0.10) mg/L in healthy group, the difference among the three groups being significant (P < 0.01). The difference of LTC(4) level was also significant when CVA group (0.65 +/- 0.62) microg/L was compared with EB group (0.39 +/- 0.61) microg/L (P < 0.05) and healthy group (0.15 +/- 0.11) microg/L (P < 0.01). The difference of histamine level in the supernatant of BALF was significant between CVA group (3.4 +/- 1.4) microg/L and EB group (1.6 +/- 1.5) microg/L (P < 0.05). CONCLUSIONS: EOS infiltration is mainly localized to the central airway in EB, with lower airway levels of LTC(4) and histamine as compared to CVA. These inflammatory features may partly explain the absence of non-specific airway hyperresponsiveness in patients with EB.
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Bronquitis/patología , Líquido del Lavado Bronquioalveolar/citología , Proteína Catiónica del Eosinófilo/metabolismo , Eosinófilos , Adulto , Asma/patología , Asma/fisiopatología , Hiperreactividad Bronquial/patología , Hiperreactividad Bronquial/fisiopatología , Bronquitis/fisiopatología , Estudios de Casos y Controles , Eosinófilos/clasificación , Eosinófilos/citología , Femenino , Humanos , Inflamación , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: Gastro-esophageal reflux (GER) is an important etiological factor inducing chronic cough. This study aims to identify the clinical features for the diagnosis of GER induced cough (GERC). METHODS: A modified Irwin's diagnostic protocol and continuous 24-hour esophageal pH monitoring were performed in 50 patients with chronic cough. Twenty patients were diagnosed as having GERC. The clinical features were compared with those of non-GER (NGER) induced cough. RESULTS: One hundred and ninety-two patients met the chronic cough criteria and were fully evaluated. The x +/- s of age was (40.6 +/- 12.1) years (range, 10 - 69 years) and 101 were males and 91 were females, with a cough history of 25 months (range, 2 - 487 months). GER accounted for 10.4% (n = 20) of the causes and was the fourth common cause of chronic cough. The mean +/- SD of age was (37.7 +/- 13.9) years (range, 10 - 60 years) in the GERC group, with a cough history of 61 months (range, 3 - 360 months). Cough associated with having meals (occurring while eating or anytime during the subsequent 2 h) was present in 13 out of the 20 patients in GERC, significantly higher than that in NGER (2 out of 23 patients) (chi2= 14.29, P < 0.01). The specificity, the positive predictive value and the sensitivity of cough associated with meals for GERC were 91.3%, 86.7% and 65.0%, respectively. Regurgitation associated symptom was present in 11 out of the 20 patients in the GERC group, not significantly different from that in the NGER group (8 out of 23 patients). Continuous 24 hour ambulatory esophageal pH measurement showed that reflux events were more common in upright [8.9 (range, 1.9 - 71.9)%] than in supine position [1.4 (range, 0 - 41.2)%] as well as at post-meal [20.2 (range, 2.1 - 84.2)%] than during meal period [1.95 (range, 0 - 51.6)%] (P < 0.01 and P < 0.05). CONCLUSION: Cough associated with having meals is of diagnostic value for GERC. The reflux events are more frequent when patients are awake, with upright position and after meals.