OBJECTIVE: To explore the clinical symptoms, lung function and airway inflammation phenotype characteristics of asthmatic patients who are sensitive to cold stimulation. METHODS: Eighty patients with newly diagnosed bronchial asthma or with mild to moderate acute exacerbation of previously diagnosed bronchial asthma but without regular treatment were selected. According to whether cold air stimulation could induce respiratory symptoms such as cough and wheeze, the patients were divided into cold-insensitive group (45 cases) and cold-sensitive group (35 cases). All the patients were treated with inhaled corticosteroid (ICS), long-acting β2 receptor agonist (LABA; salmeterol xinafoate and fluticasone propionate powder for inhalation, 50 μg/250 μg, twice daily) and montelukast sodium tablets (10 mg, once daily); short-acting β2 receptor agonist (SABA) and/or systemic glucocorticoid (prednisone acetate tablets, 10 mg, once daily; or injection of methylprednisolone sodium succinate, 40 mg) were given if necessary. Asthma Control Test (ACT) score before treatment and at 3 months of treatment was used to assess the clinical symptoms such as cough and wheeze; spirometry was performed to determine lung function impairment and recovery. Blood and induced sputum cell counts were examined to determine the characteristics of airway inflammation. RESULTS: The two groups were comparable for age, gender, BMI, proportion of smokers and allergic rhinitis before treatment. The cold-sensitive patients experienced significantly more frequent acute exacerbations than the cold-insensitive patient within 1 year before the visit ( < 0.05), but the use of SABA and glucocorticoid for symptom control during the treatment did not differ significantly between the two groups ( > 0.05). The ACT scores of the cold-sensitive group were significantly lower than those of the cold-insensitive group both before and after the treatment ( < 0.01). Compared with the cold-insensitive patients, the cold-sensitive patients had more obvious impairment of FEV1/FVC% and FEV1%pred before treatment ( < 0.01), and also showed poorer recovery after treatment ( < 0.05). The percentages of eosinophils in blood and induced sputum samples did not differ significantly between the two groups either before and after the treatment, but the percentage of neutrophils was significantly higher in the cold-sensitive group ( < 0.01). In the induced sputum samples collected before treatment, the cell populations consisted mainly of eosinophilic subtype (60%) and neutrophilic subtype (20%) in the cold-insensitive group; in the cold-sensitive patients, the sputum neutrophilic subtype cells increased significantly to 42.86% (=0.03) and the eosinophilic subtype cells were lowered to 31.43% (=0.01). CONCLUSIONS The cold-sensitive asthmatic patients experience frequent recurrent and/or aggravated symptoms and have obvious lung function impairment. Different from that in patients with classic asthma, the airway inflammatory phenotype in these patients is characterized by the domination by neutrophilic subtype.
Administration, Inhalation ; Adrenal Cortex Hormones ; therapeutic use ; Anti-Asthmatic Agents ; therapeutic use ; Asthma ; drug therapy ; physiopathology ; Cold Temperature ; adverse effects ; Cryopyrin-Associated Periodic Syndromes ; physiopathology ; Disease Progression ; Eosinophils ; Humans ; Phenotype ; Recurrence ; Sputum ; cytology

OBJECTIVE: To compare the serum glycerophospholipid levels in the inflammatory subtypes of asthma by using targeted metabolomic analysis. METHODS: Demographic and clinical data were collected from 51 patients with asthma between January 2015 and December 2015. Routine blood and sputum induction tests were performed. Eosinophilic asthma was defined as induced sputum containing ⪖ 3% eosinophils, and neutrophilic asthma, as induced sputum containing ⪖ 71% neutrophils. Serum metabolic glycerophospholipid profile was determined by liquid chromatography-mass spectrometry. Differences in glycerophospholipid levels between eosinophilic and non-eosinophilic asthma and between neutrophilic and non-neutrophilic asthma were analyzed using partial least squares discriminant analysis. RESULTS: The serum lysophosphatidylglycerol level was significantly higher in the group with ⪖ 3% eosinophils in sputum than in the group with < 3% eosinophils in sputum. The area under the receiver-operating characteristic curve was ⪖ 70%. There was no significant difference in the serum metabolic glycerophospholipid profile between the group with sputum neutrophils ⪖ 71% and the group with sputum neutrophils < 71%. CONCLUSION Serum lysophosphatidylglycerol is produced abundantly in eosinophilic asthma and may be a biomarker of eosinophilic asthma. This information is helpful for identifying and tailoring treatment for the common asthma subtypes.
Adult ; Asthma ; blood ; immunology ; Eosinophils ; immunology ; Female ; Glycerophospholipids ; blood ; Humans ; Male ; Metabolomics ; Middle Aged ; Neutrophils ; immunology ; Sputum ; cytology ; immunology

The evaluation of the quality of a sputum specimen prior to bacterial culture has been an accepted practice. However, optimal sputum criteria for pulmonary tuberculosis (TB) are not well established. We investigated indicators for sputum acceptability in tuberculosis cultures and acid-fast bacilli (AFB) smear. A post-hoc analysis of a randomized trial with 228 sputum specimens from 77 patients was conducted. In the trial, pulmonary TB suspects were requested for collecting three sputum specimens. We performed both TB study (AFB smear and M. tuberculosis culture) and Gram staining in each specimen. By using generalized estimating equations, the association between sputum characteristics and positive TB testings were analyzed. Although acceptable specimens for bacterial pneumonia showed higher TB-culture positive rates than unacceptable specimens (adjusted odds ratio [aOR]=1.66; 95% confidence interval [CI]=1.11-2.49), a specimen with > or =25 white blood cells/low-power field was the better predictor for positive M. tuberculosis cultures (aOR=2.30; 95% CI=1.48-3.58) and acid-fast bacilli smears (aOR=1.85; 95% CI=1.05-3.25). Sputum leukocytosis could be an indicator of sputum acceptability for diagnosing pulmonary tuberculosis.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bacteriological Techniques/*methods ; Female ; Humans ; Male ; Middle Aged ; Mycobacterium tuberculosis/*isolation & purification ; Reproducibility of Results ; Sensitivity and Specificity ; Sputum/cytology/*microbiology ; Tuberculosis, Pulmonary/*diagnosis/*microbiology/pathology ; Young Adult

No abstract available.
Bronchi/microbiology/pathology ; Coronavirus Infections/*microbiology/*pathology ; Delayed Diagnosis/*prevention & control ; Diagnosis, Differential ; Diagnostic Errors/*prevention & control ; False Positive Reactions ; Humans ; Male ; Middle Aged ; Reproducibility of Results ; Sensitivity and Specificity ; Specimen Handling/methods ; Sputum/*cytology/*microbiology

Neuropilin 1 (NP1) is a part of essential receptor complexes mediating both semaphorin3A (SEMA3A) and vascular endothelial growth factor (VEGF) which is one of important mediators involved in the pathogenesis of asthma. Therefore, it is possible that SEMA3A plays a role in the pathogenesis of asthma through attenuation of VEGF-mediated effects. In the present study, we aimed to evaluate expression levels of SEMA3A and NP1 using induced sputum of asthmatics and a murine model of asthma. Firstly, SEMA3A and NP1 expressions in induced sputum of asthmatics and SEMA3A and NP1 expression on bronchoalveolar lavage (BAL) cells and lung homogenates of asthmatic mice were determined. Then we evaluated the immunolocalization of VEGF receptor 1 (VEGFR1), VEGF receptor 2 (VEGFR2), and NP1 expressions on asthmatic mice lung tissue and their subcellular distributions using fibroblast and BEAS2B cell lines. Sputum SEMA3A and NP1 expressions were significantly higher in asthmatics than controls. Similarly, SEMA3A and NP1 expressions on BAL cells and lung homogenates were significantly elevated in asthmatic mice compared to control mice. Immunohistochemical analysis showed that VEGFR1, VEGFR2, and NP1 expressions were also uniformly increased in asthmatic mice. Our observations suggest that SEMA3A and NP1 may play important roles in the pathogenesis of asthma.
Animals ; Asthma/metabolism/pathology/*physiopathology ; Bronchoalveolar Lavage Fluid/cytology ; Cell Line ; Disease Models, Animal ; Female ; Fibroblasts/metabolism ; *Gene Expression Regulation ; Immunohistochemistry ; Lung/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Neuropilin-1/*genetics/metabolism ; Semaphorin-3A/*genetics/metabolism ; Sputum/metabolism ; Vascular Endothelial Growth Factor Receptor-1/metabolism ; Vascular Endothelial Growth Factor Receptor-2/metabolism

BACKGROUNDThe airway inflammation could be assessed by some noninvasive approaches. To investigate the value of eosinophil counts in induced sputum and fractional concentration of exhaled nitric oxide (FENO) for the regimen adjustment in patients with asthma, the correlation was analyzed between the two parameters and lung function parameter (forced expiratory volume in one second (FEV(1))).

METHODSSixty-five outpatients with mild to moderate non-exacerbation asthma from Beijing Chao-Yang Hospital were enrolled as treatment group. Combined medications of inhaled corticosteroids plus long-acting beta-2 agonist were administered for one year. Lung function parameters, eosinophil counts in induced sputum, concentration of exhaled nitric oxide and the Asthma Control Test scores were recorded, at regular intervals in the follow-up period. Twenty-one healthy volunteers were enrolled as control group and underwent examination of eosinophil counts in induced sputum, lung function and concentration of exhaled nitric oxide.

RESULTSSixty-three subjects from treatment group completed follow-up period for one year or longer. Mean FEV(1) value of the 63 subjects was (2.75 ± 0.54) L at baseline, (2.97 ± 0.56) L and (3.07 ± 0.52) L at month 3 and month 6, respectively, and maintained as (3.14 ± 0.51) L in the following six months. Mean FENO decreased from (61 ± 25) parts per billion (ppb) at baseline to (32 ± 19) ppb at month 3 (P < 0.05), and continued to decrease to (22 ± 12) ppb at month 6, the difference being significant when compared to both baseline and control group ((13 ± 8) ppb). Mean eosinophil counts decreased to (0.032 ± 0.011) × 10(6)/ml at month 3, which was significantly different from baseline ((0.093 ± 0.023)×10(6)/ml) and the control group ((0.005 ± 0.003)×10(6)/ml (both P < 0.05). The eosinophil counts in induced sputum correlated positively with concentration of FENO in the first six months (all P < 0.05). The concentration of FENO had a significant negative correlation with FEV(1) value (all P < 0.05) in any time point in the follow-up period. The Asthma Control Test scores were 18 ± 5, 19 ± 7, 23 ± 2, 24 ± 1 and 24 ± 1 at months 1, 3, 6, 9 and 12, respectively, which were significantly different from the score at baseline (14 ± 3) (P < 0.05). The most rapid clinical effect was observed at the second month after treatment.

CONCLUSIONEosinophil counts in induced sputum and FENO are sensitive parameters to detect airway inflammation and may be useful in evaluating the efficacy of treatment and adjusting medication regimens.

Adult ; Asthma ; immunology ; physiopathology ; Breath Tests ; Eosinophils ; physiology ; Female ; Humans ; Leukocyte Count ; Lung ; physiopathology ; Male ; Middle Aged ; Nitric Oxide ; analysis ; Sputum ; cytology

BACKGROUNDThe condition of concomitant upper lobe emphysema and lower lobe fibrosis as identified by computer tomography is known as combined pulmonary fibrosis and emphysema (CPFE). CPFE has distinct clinical characteristics compared with emphysema alone (EA) and idiopathic pulmonary fibrosis (IPF) without emphysema. However, the pulmonary inflammation characteristics of CPFE are not well known, and the differences between CPFE and the other two diseases with regards to pulmonary inflammation need to be explored. The pulmonary inflammatory characteristics were investigated in CPFE patients and compared with EA and IPF.

METHODSFraction exhaled nitric oxide (Fe,NO) and differential cell counts, the concentrations of monokine induced by interferon gamma (MIG/CXCL9), interferon-inducible protein 10 (IP-10/CXCL10), and interferon-inducible T cell alpha chemoattractant (I-TAC/CXCL11) were measured in induced sputum obtained from subjects with CPFE (n = 22), EA (n = 22), IPF (n = 14), and healthy volunteers (HV, n = 12). In addition, immunohistochemistry was used to quantify the expression of nitric oxide synthases in alveolar macrophages in 23 lung tissues from patients and control subjects.

RESULTSThe CPFE group had higher alveolar NO than subjects in the EA and HV groups (P = 0.009, P = 0.001, respectively) but not than the IPF group (P > 0.05). Numbers of sputum eosinophils were significantly elevated in CPFE and IPF groups compared with the HV group (P = 0.001, P = 0.008). In contrast, eosinophil counts in EA group did not differ from those in the HV group. Compared with the EA and HV groups, the CPFE group had a lower concentration of I-TAC/CXCL11 in sputum supernatants (P = 0.003, P = 0.004). Immunoreactivity for inducible nitric oxide synthase (iNOS) was higher in the CPFE group than in the EA group (P = 0.018, P = 0.006, respectively).

CONCLUSIONSThe pulmonary inflammation of CPFE group is more similar to IPF group, while the distal airway inflammation is more significant in CPFE and IPF groups than in EA group. Lung eosinophil cell infiltration and high NOS expression in alveolar macrophage might participate in this pathogenesis.

Aged ; Breath Tests ; Chemokines ; analysis ; Female ; Humans ; Immunohistochemistry ; Lung ; pathology ; Male ; Middle Aged ; Nitric Oxide ; analysis ; Nitric Oxide Synthase Type II ; analysis ; Pneumonia ; etiology ; pathology ; Pulmonary Emphysema ; pathology ; Pulmonary Fibrosis ; pathology ; Sputum ; cytology

BACKGROUNDChronic obstructive pulmonary disease (COPD) is a progressive disease associated with a cellular inflammatory response mostly concerned with cigarette smoking. Chemokine receptors CCR1/5 play an important role in the inflammatory cells recruitment in the lung of COPD patients. The aim of this study was to determine the impact of cigarette smoking on the expression of CCR1/5 on inflammatory cells in induced sputum, and the relationship between the receptors expression and COPD severity.

METHODSDifferential cells in induced sputum were counted and the optical densities of CCR1 and CCR5 on inflammatory cells in induced sputum from COPD patients (n = 29), healthy smokers (n = 11), and nonsmokers (n = 6) were measured using immunocytochemistry. Concentrations of CCL3, the ligand of CCR1/5, in supernatant of induced sputum were detected by enzyme-linked immunosorbent assay.

RESULTSThe expressions of CCR1 and CCR5 on inflammatory cells in healthy smokers were significantly higher than those in nonsmokers, and the expression of CCR1 in patients with COPD was significantly increased when compared with nonsmokers but not healthy smokers. The expressions of CCR1 and CCR5 on inflammatory cells in severe and very severe COPD patients were higher compared with mild and moderate COPD patients. CCL3 level was positively correlated with the total cell counts in induced sputum and smoking history, and negatively correlated with percentage of predicted FEV(1).

CONCLUSIONSCigarette smoking could increase the expression of CCR1 on the inflammatory cells. Both CCR1 and CCR5 expressions on the inflammatory cells in induced sputum could be associated with COPD severity.

Adult ; Aged ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Pulmonary Disease, Chronic Obstructive ; immunology ; metabolism ; Receptors, CCR1 ; metabolism ; Receptors, CCR5 ; metabolism ; Smoking ; adverse effects ; Sputum ; cytology ; immunology

OBJECTIVETo establish the method of cytological examination and the normal reference values for hypertonic saline solution-induced sputum of healthy children (age range from 5 to 15 years) with physical examination in Guangzhou.

METHODA total of 352 children, 5 to 15 years old, were enrolled from primary school and middle school in Guangzhou from January to December, 2010. All subjects completed a standardized questionnaire on the presence of respiratory, allergic symptoms and family history, the medical history and the physical examination was performed by doctors, lung function (forced expiratory volume at 1 s in predicted normal, FEV(1)%) was determined. There were 266 healthy children (137 males, 129 females) who were selected and undergone hypertonic saline solution induction of sputum, and cytological examination was performed. Hypertonic saline (5%) was nebulized and inhaled for 15 - 30 min. No expectoration within 30 min was defined as failure, and the procedure was terminated. The part of opaque and higher density sputum samples was detected by cytology. The proportion of neutrophils, lymphocytes, eosinophils, macrophages and monocytes was calculated. This study was approved by the institutional Ethics Review Committee of First Affiliated Hospital of Guangzhou Medical College. Informed consent was obtained from the legal guardians of all participants following a detailed description of the purpose and potential benefits of the study.

RESULTThere were 175 subjects' induced sputum specimens (175/266, 65.8%), non-qualified sputum samples were obtained from 16 of the subjects. The proportions of median (IQR) of lymphocytes were 0.012 (0.020), 95%CI were ranged from 0.015 to 0.022; neutrophils 0.207 (0.330), 95%CI 0.266 - 0.356 macrophages 0.761 (0.327), 95%CI 0.607 - 0.699; eosinophils 0.004 (0.019), 95%CI 0.013 - 0.022. There were no significant differences in proportions of cytological findings of female or male, different age groups and second-hand smoking or not (all P > 0.05). The incidence of adverse event was 4.40% (7/159).

CONCLUSIONThe method and the preliminary data may be used for research, diagnosis and treatment of patients with chronic cough and airway inflammation.

Adolescent ; Child ; Child, Preschool ; China ; Cough ; diagnosis ; physiopathology ; Eosinophils ; cytology ; Female ; Forced Expiratory Volume ; Humans ; Leukocyte Count ; Lymphocyte Count ; Lymphocytes ; cytology ; Male ; Monocytes ; cytology ; Neutrophils ; cytology ; Reference Values ; Saline Solution, Hypertonic ; chemistry ; Sputum ; cytology ; metabolism

OBJECTIVETo discuss the effect of different positive criteria on the sensitivity and specificity of sputum cytology screening for lung cancer among Yunnan tin miners.

METHODS9223 Yunnan tin miners who received at least one annual sputum cytology screening for lung cancer during the period between 1992 and 1999 were recruited in the study. At time of enrollment, all participants were aged over 40 years old, had at least 10 years of employment as an underground miner and(or) smelter, and had not been diagnosed with malignancy. In our study, a true positive was categorized as having at least one prior positive sputum screening and a diagnosis of lung cancer, while a true negative, by our definition, signified negative sputum examinations and no diagnosis of lung cancer during the follow up time. Based on different positive criteria, sensitivity and specificity of sputum cytology were computed and receiver operating characteristic (ROC) curve analysis was conducted. Z statistic was used to test the differences of the area under ROC based on Hanley and McNeil method.

RESULTSBy the end of following up on December 31, 2001, a total 500 lung cancer cases were diagnosed among 9223 participants: most were squamous cell carcinoma (55.8% (222/398)) and central lung cancers (68.5% (316/461)). 150 lung cancer cases had a previous positive sputum screening result. When positive criteria were taken as grave atypical metaplasia, moderate atypical metaplasia and slight atypical metaplasia, the corresponding sensitivities were 30.0% (150/500), 36.4% (182/500), 53.0% (265/500) respectively; while the corresponding specificities were 98.9% (8628/8723), 95.1% (8611/8723), 77.9% (7033/8723) respectively. The areas under ROC curve according to different positive criterias were 0.645 (95%CI: 0.635 - 0.654), 0.657 (95%CI: 0.668 - 0.667), 0.655 (95%CI: 0.645 - 0.664) respectively. There were no significant differences found in the comparisons between grave and moderate atypical metaplasia, grave and slight atypical metaplasia, moderate and slight atypical metaplasia(Z statistics were 0.780, 0.645, 0.209 respectively, all P values > 0.05).

CONCLUSIONWhile the standard of positive criteria for diagnosis of lung cancer decreased, the sensitivity of sputum cytology screening increased and the specificity decreased. Since there were no significant differences of accuracy for different positive criteria.

Cytodiagnosis ; methods ; standards ; Female ; Humans ; Lung Neoplasms ; diagnosis ; Male ; Mass Screening ; methods ; Sensitivity and Specificity ; Sputum ; cytology