Exhaled breath analysis for the discrimination of asthma and chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) and asthma are the most common chronic respiratory diseases. In middle-aged and elderly patients, it is difficult to distinguish between COPD and asthma based on clinical symptoms and pulmonary function examinations in clinical practice. Thus, an accurate and reliable inspection method is required. In this study, we aimed to identify breath biomarkers and evaluate the accuracy of breathomics-based methods for discriminating between COPD and asthma. In this multi-center cross-sectional study, exhaled breath samples were collected from 89 patients with COPD and 73 with asthma and detected on a high-pressure photon ionization time-of-flight mass spectrometry (HPPI-TOFMS) platform from 20 October 2022, to 20 May 2023, in four hospitals. Data analysis was performed from 15 June 2023 to 16 August 2023. The sensitivity, specificity, and accuracy were calculated to assess the overall performance of the volatile organic component (VOC)-based COPD and asthma discrimination models. Potential VOC markers related to COPD and asthma were also analyzed. The age of all participants ranged from to 18-86 years, and 54 (33.3%) were men. The age [median (minimum, maximum)] of COPD and asthma participants were 66.0 (46.0, 86.0), and 44.0 (17.0, 80.0). The male and female ratio of COPD and asthma participants were 14/75 and 40/33, respectively. Based on breathomics feature selection, ten VOCs were identified as COPD and asthma discrimination biomarkers via breath testing. The joint panel of these ten VOCs achieved an area under the curve of 0.843, sensitivity of 75.9%, specificity of 87.5%, and accuracy of 80.0% in COPD and asthma discrimination. Furthermore, the VOCs detected in the breath samples were closely related to the clinical characteristics of COPD and asthma. The VOC-based COPD and asthma discrimination model showed good accuracy, providing a new strategy for clinical diagnosis. Breathomics-based methods may play an important role in the diagnosis of COPD and asthma.

Comparison of air pollutant-related hospitalization burden from AECOPD in Shijiazhuang, China, between heating and non-heating season.

Few researches have been investigated on the effects of ambient air pollutants from coal combustion on acute exacerbation of chronic obstructive pulmonary disease (AECOPD) hospitalizations. The whole time series was split into heating season and non-heating season. We used a quasi-Poisson generalized linear regression model combined with distributed lag non-linear models (DLNMs) to estimate the relative cumulative risk and calculate the air pollutant hospitalization burden of AECOPD for lag 0-7 days in heating season and non-heating season. There were higher PM2.5, PM10, NO2, SO2, and CO concentrations in heating seasons than non-heating season in Shijiazhuang; however, O3 was higher in non-heating season than heating season. The AECOPD-associated relative cumulative risks for PM2.5, PM10, NO2, and SO2 for lag 0-7 days were significantly positively associated with hospitalization in heating and non-heating season; we found that the cumulative relative risk of NO2 was the greatest in every 1 unit of air pollutants during the heating season and the cumulative relative risk of SO2 was the greatest during the non-heating season. The results showed that 17.8%, 12.9%, 1.7%, 16.7%, and 10.5% of AECOPD hospitalizations could be attributable to PM2.5, PM10, SO2, NO2, and CO exposure in heating season, respectively. However, the results showed that 19.5%, 22.4%, 15%, 8.3%, and 10.4% of AECOPD hospitalizations could be attributable to PM2.5, PM10, SO2, NO2, and O3 exposure in non-heating season, respectively. The attributable burden of AECOPD hospitalization in heating season and non-heating season are different. PM2.5, PM10, NO2, and CO are the main factors of heating season, while PM10, PM2.5, SO2, and O3 are the main factors of non-heating season. In conclusions, the centralized heating can change the influence of attributable risk. When government departments formulate interventions to reduce the risk of acute hospitalization of chronic obstructive pulmonary disease (COPD), the influence of heating on disease burden should be considered.

The hospitalization attributable burden of acute exacerbations of chronic obstructive pulmonary disease due to ambient air pollution in Shijiazhuang, China.

Few studies have investigated the acute exacerbations of chronic obstructive pulmonary disease (AECOPD)-associated attributable burden under exposure to high levels of air pollution among Asians. Data on hospitalization for AECOPD, air pollution and meteorological factors from 1 January 2013 to 31 December 2016 were collected in Shijiazhuang, China. We used a Poisson generalized linear regression model combined with a distributed lag nonlinear model (DLNM) to evaluate the relative cumulative risk for a lag of 0-7 days and examined the potential effect modifications by age and sex via stratification analyses, controlling for long-term trends, seasonal patterns, meteorological factors, and other possible confounders. Then, we computed hospitalization percentages attributable to air pollutants. The AECOPD-associated relative cumulative risks for PM2.5, PM10, NO2, SO2, and CO for a lag of 0-7 days were significantly positively correlated with hospitalization. The associations were stronger in females and retired patients. The NO2 Cum RR of AECOPD admission was the greatest. A 10µg/m3 increase in daily NO2 concentration was associated with 6.7% and 5.7% increases in COPD hospitalizations in the retired and female groups, respectively. The results showed that 13%, 9.4%, 1.7%, 9.7%, and 8.8% of AECOPD hospitalizations were attributable to exposure to PM2.5, PM10, SO2, NO2, and CO, respectively. If the air pollutant concentration was reduced to the 24-h average grade II levels of NAAQS of China, the AECOPD attributable percentage for PM2.5 and PM10 would decrease by 80%. The air pollutants PM2.5, PM10, SO2, NO2, and CO were significantly relevant to AECOPD-associated hospitalization. The associations differed by individual characteristics. The retired and female populations were highly vulnerable.

The effect and burden modification of heating on adult asthma hospitalizations in Shijiazhuang: a time-series analysis.

BACKGROUND: Previous studies have found associations between asthma morbidity and air pollution especially in young population, (PLoS One 12:e0180522, 2017; Can J Public Health 103:4-8, 2012; Environ Health Perspect 118:449-57, 2010; Am J Respir Crit Care Med 182:307-16, 2010; J Allergy Clin Immunol 104:717-22, 2008; J Allergy Clin Immunol 104:717-22, 1999; Environ Res 111:1137-47, 2011) but most of them were conducted in areas with relatively low air pollutant level. Moreover, very few studies have investigated the effect and burden modification of heating season during which the ambient air pollution level is significantly different from that during non-heating season in north China. OBJECTIVES: This study aimed to evaluate the effect and burden modification of heating on short-term associations between adult asthma hospitalizations and ambient air pollution in the north China city of Shijiazhuang. METHODS: Generalized additive models combined with penalized distributed lag nonlinear models were used to model associations between daily asthma hospitalizations and ambient air pollutants from 1 January 2013 to 16 December 2016 in Shijiazhuang city, adjusting for long-term and seasonality trend, day of week, statutory holiday, daily mean air pressure and temperature. Attributable risks were calculated to evaluate the burden of asthma hospitalizations due to air pollutants exposure. The effect of pollutants on hospitalization and the attributable measures were estimated in heating and non-heating season separately and the comparisons between the two seasons were conducted. RESULTS: All pollutants demonstrated positive and significant impacts on asthma hospitalizations both in heating season and non-heating season, except for O3 in heating season where a negative association was observed. However, the differences of the pollutant-specific effects between the two seasons were not significant. SO2 and NO2 exposure were associated with the heaviest burden among all pollutants in heating season; meanwhile, PM10 and PM2.5 were associated with the heaviest burden in heating season. CONCLUSIONS: In conclusion, we found evidence of the effect of ambient air pollutants on asthma hospitalizations in Shijiazhuang. The central heating period could modify the effects in terms of attributable risks. The disease burden modification of heating should be taken into consideration when planning intervention measures to reduce the risk of asthma hospitalization.

Comparative transcriptomics analyses of the different growth states of multidrug-resistant Acinetobacter baumannii.

Multidrug-resistant (MDR) Acinetobacter baumannii is an important bacterial pathogen commonly associated with hospital acquired infections. A. baumannii can remain viable and hence virulent in the environment for a long period of time due primarily to its ability to form biofilms. A total of 459 cases of MDR A. baumannii our hospital collected from March 2014 to March 2015 were examined in this study, and a representative isolate selected for high-throughput mRNA sequencing and comparison of gene expression profiles under the biofilm and exponential growth conditions. Our study found that the same bacteria indeed exhibited differential mRNA expression under different conditions. Compared to the rapidly growing bacteria, biofilm bacteria had 106 genes upregulated and 92 genes downregulated. Bioinformatics analyses suggested that many of these genes are involved in the formation and maintenance of biofilms, whose expression also depends on the environment and specific signaling pathways and transcription factors that are absent in the log phase bacteria. These differentially expressed mRNAs might contribute to A. baumannii's unique pathogenicity and ability to inflict chronic and recurrent infections.

Prevalence, severity and risk factors of asthma, rhinitis and eczema in a large group of Chinese schoolchildren.

BACKGROUND: There is a lack of information on the prevalence, severity and risk factors of asthma, rhinitis and eczema in Chinese children. OBJECTIVE: To establish baseline data for a major longitudinal study of factors affecting asthma, rhinitis and eczema in a large group of children from the industrialized city of Shijiazhuang, China. METHODS: We used the International Study of Asthma and Allergies in Childhood questionnaire and studied 10 338 children, ages 6-18, from Shijiazhuang. RESULTS: The prevalence of childhood asthma, rhinitis and eczema is 1.2%, 13.5% and 11.8%, respectively. Boys had higher prevalence of these conditions than girls and younger children had higher prevalence of asthma and eczema but lower prevalence of rhinitis than older children. Breastfed children had lower prevalence of asthma and rhinitis, but not eczema, than non-breastfed children. Overweight children had higher prevalence of asthma and rhinitis than those who were not overweight. Children exposed to paternal smoking had higher prevalence of rhinitis and eczema than those not exposed; children exposed to pets had higher prevalence of asthma and rhinitis than those not exposed. CONCLUSIONS: The prevalence of asthma in this study group is low, but the prevalence of rhinitis is high, and could be considered a major public health problem. The prevalence of asthma, rhinitis and eczema is generally higher in boys and younger children generally have higher prevalence of asthma and eczema but lower prevalence of rhinitis. Exposure to pets is a risk factor for rhinitis, being overweight is a risk factor for asthma and rhinitis, and exposure to parental smoking is a risk factor for asthma, rhinitis and eczema in these children.

[Effect of selective phosphodiesterase 4 inhibitors on nuclear factor kappa B, tumor necrosis factor-α and interleukin-8 expression in peripheral blood mononuclear cells in rheumatoid arthritis with interstitial lung disease].

OBJECTIVE: To investigate the effect of selective phosphodiesterase (PDE) 4 inhibitors on nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNFα) and interleukin-8 (IL-8) secreted by peripheral blood mononuclear cells (PBMCs) in patients diagnosed as rheumatoid arthritis with interstitial lung disease (RA-ILD). METHODS: PBMCs isolated from 15 healthy volunteers (group A) and 20 patients with untreated active RA-ILD (group B) were cultured in vitro. PBMCs from healthy subjects were considered as normal control. PBMCs from RA-ILD patients were divided into four groups with different treatment: blank group (B1), theophylline group (B2), selective PDE4 inhibitor rolipram group (B3), and glucocorticoid group (B4) with dexamethasone. The expression of NF-κB was determined by immunocytochemical staining, and the levels of TNFα and IL-8 in the culture supernatant were detected by enzyme linked immunosorbent assay (ELISA). RESULTS: (1) The activity of NF-κB and the levels of TNFα and IL-8 in group B1 were significant higher than that in group A (P < 0.01). Compared with group B1, three parameters above were similar to those in group B2 (P > 0.05), while group B3 and group B4 had significant decreased levels of three parameters (P < 0.01); IL-8 level in group B4 was significantly lower than that in group B3 (P < 0.05). (2) TNFα and IL-8 levels were positively correlated with NF-κB activity in group B (r = 0.902 and 0.735, P < 0.01 respectively). (3) The reduction of TNFα and IL-8 levels were positively correlated with reduction of NF-κB activity after intervention of rolipram in group B3 (r = 0.874, P < 0.01; r = 0.561, P < 0.05 respectively). CONCLUSION: NF-κB activation and proinflammatory cytokines were involved in the pathogenesis of RA-ILD. selective PDE4 inhibitors may inhibit the production of inflammatory cytokines by inhibiting the activity of the transcription factor NF-κB in PBMC, thus inhibiting the inflammatory reaction of RA-ILD.

[The effect of controlled mechanical ventilation on the diaphragm of rats].

OBJECTIVE: To investigate the effect of controlled mechanical ventilation (CMV) on the diaphragm of rats, and therefore to understand the theoretic basis of difficulty weaning due to dysfunction and morphology in diaphragm induced by inappropriate mechanical ventilation. METHODS: Twenty-four adult male SD rats were randomly assigned into 3 experimental groups: a control group, a 18 h CMV group, and a 24 h CMV group. Trans-diaphragmatic pressure (Pdi), maximal trans-diaphragmatic pressure (Pdimax), diaphragm electromyogram (EMGdi), and diaphragm muscle force were measured during CMV at various stimulation frequencies. Morphological changes of the diaphragm myofibril were observed by transmission electron microscopy. Myosin heavy chain (MHC) isoform expression were analyzed with SDS-glycerol PAGE and Western blotting. RESULTS: The Pdimax in the 18 h CMV group and the 24 h CMV group [(8.98+/-0.55, 6.12+/-0.53) cm H2O, 1 cm H2O=0.098 kPa] was significantly reduced (F=82.35, P<0.01) compared with the control group [(14.92+/-0.16) cm H2O]. The Fc and the H/L decreased significantly. At the stimulation frequency of 100 Hz, the diaphragm muscle force in the 18 h CMV group and 24 h CMV group [(84.11+/-0.43) N, (52.65+/-0.64) N, respectively] decreased compare with the control [(98.13+/-0.50) N, F=15.02, P<0.01]. The proportion of MHC2A decreased in the 24 h group compared with control. The ultrastructural changes of the diaphragm was observed in the 24 h CMV group, such as disrupted myofibrils, increased numbers of lipid vacuoles in the sarcoplasm, and abnormally small mitochondria containing focal membrane disruptions. CONCLUSION: Short-term CMV induced diaphragm fatigue and altered the function and morphology of diaphragm in SD rats. Diaphragmatic dysfunction induced by CMV maybe one of the important reasons for difficult weaning.

[Effects of leukotriene receptor antagonists on vascular endothelial growth factor and its receptors in a sensitized rat model].

OBJECTIVE: To investigate the effect of montelukast (MK) on airway inflammation and remodeling in asthmatic rats, and to explore the regulating role of MK on vascular endothelial growth factor (VEGF) and its receptors. METHODS: Twenty-four male Sprague-Dawley rats were randomly divided into 3 groups, a control group (n = 8), an asthmatic group (n = 8) and a MK treated group (n = 8). The rats were sensitized with ovalbumin and AL (OH3), and repeatedly exposed to aerosolized ovalbumin. Airway reactivity of the animals were measured by animal lung function meter. VEGF levels and leukotriene D(4) (LTD(4)) in serum were measured by enzyme linked-immunosorbent assay (ELISA). The pathologic changes of bronchi and the lung tissue were evaluated, and the expression of VEGF and its acceptors was analyzed with immunohistochemistry. The vascular counts and vascular smooth muscle thickness were measured by using image analysis system. RESULTS: The bronchial provocation test showed that, in the asthmatic group, the average expiratory resistance increased remarkably. The serum levels of VEGF and LTD(4) in the asthmatic group were 31 +/- 6 and 11 +/- 4 respectively, significantly higher than those in the control group (17 +/- 5 and 6.1 +/- 0.7) respectively and in the MK group (15 +/- 4 and 9.8 +/- 1.6) respectively. (F 63.78, 39.56 all P < 0.01). Immunohistochemistry showed that, the expression of VEGF, VEGFR(1) and VEGFR(2) in the asthmatic group were increased, as compared to those in the control group and the treated group. The vascular counts were 14 +/- 2, 22 +/- 2 and 16 +/- 4 in the control, the asthmatic, and the treated groups. CONCLUSIONS: VEGF and its receptors were over-expressed in the sensitized rat model, and involved in angiogenesis and airway remodeling. MK may be effective in reducing allergic airway inflammation and airway remodeling through VEGF and VEGFR.

[Study on hemodynamic changes and cardiac troponin I level in pig model of acute experimental pulmonary embolism].

OBJECTIVE: To evaluate the hemodynamic effects and cardiac troponin I (cTn I), creatine kinase-MB (CK-MB), myoglobin (Mb) releasing kinetics of acute experimental pulmonary embolism of pigs. METHODS: Sixteen juvenile pigs, of either gender and weighing 30 to 40 kg were studied, 8 in the embolism group and 8 in the control group. The 8 embolism animals received 0.1 g/kg polystyrene beads (diameter range 0.65 to 0.67 mm) suspended in 0.9% saline by venous injection. Pulmonary arterial pressure (PAP), systemic arterial pressure (SAP), pulmonary capillary wedged pressure (PCWP), cardiac output (CO), blood gases and serum cTn I, CK-MB, and Mb were measured before and immediately, 30 min, 1 hour, 2 hour, and 3 hour after acute pulmonary embolism. RESULTS: PAP was increased to 2 - 3 fold of the baseline and the control level immediately, and then decreased to the baseline level in 2 to 3 hours. Serum cTn I and Mb increased significantly after embolism and remained at a higher level through the 3 hour experimental procedure. The CK-MB was not changed after acute pulmonary embolism. CONCLUSIONS: Acute pulmonary embolism caused lung gas exchange abnormality and acute pulmonary hypertension. The hemodynamic effects of acute pulmonary embolism include injury to the myocardial cells and releasing of cTn I and Mb to blood stream. cTn I can be detected in the early phase of acute pulmonary embolism, and maybe a useful marker in diagnosis and management of acute pulmonary embolism.

[Detection of thromboxane B2, 6-keto-prostaglandin F1alpha and anticardiolipin antibody in patients with obstructive sleep apnea-hypopnea syndrome].

OBJECTIVE: To observe the changes of thromboxane B(2) (TXB(2)), 6-keto-prostaglandin F1alpha (6-K-PGF1alpha) and anticardiolipin antibody (ACA) in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) before and after institution of nasal continuous positive airway pressure (nCPAP). METHODS: Sixty cases of OSAHS confirmed by polysomnography (PSG) were selected as the trial group, and 20 normal donors without OSAHS were recruited as the control group. Nineteen patients with severe OSAHS were treated by nCPAP. Plasma levels of TXB(2), 6-K-PGF1alpha were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: Plasma (serum) level of TXB(2) (ACA) was significantly higher in patients with moderate to severe OSAHS than that in control group (P < 0.01), and nCPAP therapy decreased its level significantly (P < 0.01). Plasma level of 6-K-PGF1alpha was significantly lower than that in the control group (P < 0.01), and nCPAP therapy increased its level significantly (P < 0.01). TXB(2) and ACA were correlated positively with AHI, and negatively with minimal oxygen saturation (P < 0.01). 6-K-PGF1alpha was correlated negatively with AHI, and positively with minimal oxygen saturation (P < 0.01). CONCLUSIONS: The results indicate that patients with OSAHS are susceptible to thromboembolism disease. TXB(2), 6-K-PGF1alpha, ACA may be associated with the high prevalence of thromboembolism in patients with OSAHS. nCPAP therapy is effective in correcting TXB(2), 6-K-PGF1alpha, ACA.

[Changes of the platelet function and serum anticardiolipin antibody in patients with pulmonary thromboembolism].

OBJECTIVE: To explore the changes of the platelet function and serum anticardiolipin antibody (ACA) in patients with pulmonary thromboembolism (PTE). METHODS: Forty-eight patients with PTE diagnosed by spiral computed tomographic pulmonary angiography (CTPA) were included as the trial group, while 20 person in which PTE was excluded served as the control group. P-selectin, and GPIIb/IIIa expressed on platelets were measured by flow cytometry, and plasma TXB(2), 6-Keto-PGF1alpha, vWF, D-dimer and serum ACA were measured by ELISA and the changes of these parameters were compared 1 week later. RESULTS: In the trial group, the levels of P-selectin, GPIIb/IIIa, TXB(2), vWF, D-dimer and T/K were significantly higher than those in the control group (P < 0.01). But the plasma level of 6-Keto-PGF1alpha in the patients with PTE was significantly lower than that in the control group (P < 0.01). The levels of ACA-IgG and ACA-IgA were significantly higher than those in the control group (P < 0.01). After therapy the level of 6-Keto-PGF1alpha was significantly higher than that before therapy (P < 0.01), and other parameters were significantly lower than those before therapy (P < 0.01). P-selectin, GPIIb/IIIa and vWF were positively correlated with D-dimer (P < 0.01). CONCLUSION: Endothelium damage, platelet activation and hypercoagulation combined with fibrinolytic activation occur in patients with PTE.

[Significance of the changes of platelet activation and fibrinolytic activity in patients with obstructive sleep apnea-hypopnea syndrome].

OBJECTIVE: To investigate the changes of platelet activation, coagulability, and fibrinolytic activation in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) before and after the institution of nasal continuous positive airway pressure (nCPAP). METHODS: Fifty-eight cases of OSAHS confirmed by polysomnography (PSG) were selected as the trial group, 20 subjects without OSAHS were recruited as the control group. Eleven patients with severe OSAHS were treated by nCPAP. Plasma GMP-140, GPIIb/IIIa and D-dimer were measured by ELISA. RESULTS: Plasma levels of GMP-140, GPIIb/IIIa and D-dimer were significantly higher in patients with moderate to severe OSAHS than those in the control group, P < 0.05, and nCPAP therapy decreased their levels significantly, P < 0.001. GMP-140, GPIIb/IIIa and D-dimer were correlated positively with AHI, and negatively with minimal oxygen saturation, P < 0.001. CONCLUSIONS: Our findings suggest that activation of platelet and coagulation system with fibrinolytic activation may be associated with the high prevalence of cerebrovascular and cardiovascular events in patients with OSAHS. nCPAP therapy is effective in correcting these coagulatory and fibrinolytic abnormalities.

[A study on viral infections in patients with chronic obstructive pulmonary disease].

OBJECTIVE: To study the relation between viral infection and chronic obstructive pulmonary disease (COPD), and the role of viral infection in the pathogenesis of COPD. METHODS: (1)Serum samples from 91 patients with acute exacerbation of COPD (Group A), 42 patients with stable COPD (Group B) and 25 healthy subjects (Group C) were tested for specific IgM and IgG for respiratory syncytial virus (RSV) herpes simplex virus type 1 (HSV-1) parainfluenza virus(PIV),adenovirus (ADV) and cytomegalovirus (CMV) with an indirect enzyme linked immunosorbent assay (ELISA). (2) T lymphocyte subsets (CD(3) CD(4) and CD(8)) were studied by flow cytometry in patients with IgM positivity (Group D n = 28) and patients in Group C. RESULTS: (1) The positive rates of IgM were significantly different (P < 0.001) in group A (12%, 8%, 6%, 2%, 3% for RSV HSV-1 PIV ADV and CMV) as compared to group B (0%, 0%, 0%, 0%, 0%) and group C (0%, 0%, 0%, 0%, 0%). There was no significant difference in the positive rate of IgG between group A (47%, 41%, 12%, 14%, 10%) and group B (43%, 33%, 12%, 7%, 7%, P > 0.05), but the positive rates of IgG in group A and group B were significantly different (P < 0.01) as compared to group C (0%, 8%, 0%, 0%, 0%) (2)In group D the expression of CD(4) and CD(4)/CD(8) were significantly lower, the expression of CD(8) was significantly higher (P < 0.01) than those in group C but the expression of CD(3) was not significantly different (P > 0.05). CONCLUSION: Viral infection was common in acute exacerbation of COPD, and related to the pathogenic mechanism of COPD.