Relationship between Fractional Exhaled Nitric Oxide Level and Efficacy of Inhaled Corticosteroid in Asthma-COPD Overlap Syndrome Patients with Different Disease Severity

This study explored the relationship between the fractional exhaled nitric oxide (FeNO) level and the efficacy of inhaled corticosteroid (ICS) in asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) patients with different disease severity. A total of 127 ACOS patients with ACOS (case group) and 131 healthy people (control group) were enrolled in this study. Based on the severity of COPD, the ACOS patients were divided into: mild ACOS; moderate ACOS; severe ACOS; and extremely severe ACOS groups. We compared FeNO levels, pulmonary function parameters including percentage of forced expiratory volume in 1 second (FEV1) to predicted value (FEV1%pred), ratio of FEV1 to forced vital capacity (FEV1/FVC), inspiratory capacity to total lung capacity (IC/TLC) and residual volume to total lung capacity (RV/TLC), arterial blood gas parameters, including PH, arterial partial pressure of oxygen (PaO₂) and arterial partial pressure of carbon dioxide (PaCO₂), total serum immunoglobulin E (IgE), induced sputum eosinophil (EOS), plasma surfactant protein A (SP-A), plasma soluble receptor for advanced glycation end products (sRAGE), sputum myeloperoxidase (MPO), sputum neutrophil gelatinase-associated lipocalin (NGAL) and Asthma Control Test (ACT) scores, and COPD Assessment Test (CAT) scores. Compared with pre-treatment parameters, the FeNO levels, RV/TLC, PaCO₂, total serum IgE, induced sputum EOS, plasma SP-A, sputum MPO, sputum NGAL, and CAT scores were significantly decreased after 6 months of ICS treatment, while FEV1%pred, FEV1/FVC, IC/TLC, PH, PaO₂, plasma sRAGE, and ACT scores were significantly increased in ACOS patients with different disease severity after 6 months of ICS treatment. This finding suggests that the FeNO level may accurately predict the efficacy of ICS in the treatment of ACOS patients.

Association between human beta defensin-1 single nucleotide polymorphisms and susceptibility to pulmonary tuberculosis / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the possible association between the SNP in the 5' untranslated region (5' UTR) of the human beta defensin 1 (DEFB1) gene and the susceptibility to pulmonary tuberculosis (PTB) in Chinese Han population.</p><p><b>METHODS</b>In this case-control study, venous blood was collected from 102 patients with PTB and 148 healthful persons. Genomic DNA was extracted using whole blood DNA extraction kit. The -52A/G, -44C/G and -20A/G SNP were genotyped by PCR-directed sequencing. The genotypes and allele frequency were analyzed using the χ(2) test. The linkage disequilibrium and haplotype were analyzed by SHEsis software.</p><p><b>RESULTS</b>A total of 102 patients with PTB (69 males and 33 females, (53.42 ± 20.22) years old) and 148 healthy control cases (95 males and 53 females, (50.67 ± 14.53) years old) were enrolled, with no difference in gender and age (all P values > 0.05). DEFB1 -44 CC genotype was significantly more frequently found in PTB patients than in control group (81.4% (83/102) vs 66.9% (99/148), χ(2) = 5.114, P < 0.05, OR = 2.096, 95%CI: 1.095 - 4.011), so was -44C allele (89.2% (182/204) vs 80.4% (238/296), χ(2) = 6.975, P < 0.05, OR = 1.576, 95%CI: 1.086 - 2.286). No difference in -52 A/G and -20 A/G SNP was observed between the two groups. The proportion of the GGG (-52/-44/-20) haplotype was lower in PTB patients than in the control group (0.030 vs 0.081, χ(2) = 5.629, P < 0.05, OR = 0.348, 95%CI: 0.140 - 0.863). No linkage disequilibrium was found among the SNP of the three sites (D' values were 0.132, 0.064, 0.088; r(2) values were 0.003, 0.002, 0.003; all P values > 0.05).</p><p><b>CONCLUSION</b>These results suggest that the SNP of DEFB1 5' UTR is associated with susceptibility to PTB in Chinese Han population. -44 C→G SNP and the related haplotype (GGG) might play a protective role in the pathogenesis of PTB.</p>

Changes of adrenomedullin 2/intermedin in the lung of rats with chronic hypoxic pulmonary hypertension / 中国应用生理学杂志

<p><b>AIM</b>To investigate the changes and probable roles of adrenomedullin2/intermedin (AIDM2/IMD), a novel micromolecular bioactive peptide, in the lungs of rats with chronic hypoxic pulmonary hypertension.</p><p><b>METHODS</b>Twenty male SD rats were randomly divided into normal control group (NC) and normobaric hypoxia group (4H). The protein levels of ADM and ADM2/IMD) in the plasma and lung were measured by radioimmunoassay and immunohistochemistry. The mRNA expressions of ADM, ADM2/IMD and their receptors C (RLR, RAMP1, RAMP2 and RAMP3 in the lung tissue were determined by reverse transcription-polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>(1) The rat model of chronic pulmonary hypertension was confirmed by the increased mean pulmonary arterial pressure (mPAP) and weight ratio of right ventricle to left ventricle plus septum [RV/(LV + S)] in 4H group compared to NC group. (2) The concentrations of ADM in the plasma and lung homogenate of 4H group were 2.3 and 3.2 folds of NC group, respectively (all P < 0.01). The levels of ADM2/IMD were higher 89.6% and 45.0% in the plasma and lung homogenate of 4H group than those of NC group (respectively, P < 0.01, P < 0.05). (3) The mRNA expressions of ADM2/IMD and ADM in the lung of 4H group were up-regulated (respectively, P < 0.01, P < 0.05 vs. NC group). The expressions of CRLR and RAMP1 mRNAs were down-regulated (all P < 0.01 vs. NC group), while the levels of RAMP2 and RAMP3 mRNAs were no significant difference between the two groups. (4) The strong ADM2/IMD immunostaining was detected in the endothelial and adventitial cells of the rat pulmonary arteriole.</p><p><b>CONCLUSION</b>ADM2/IMD, like its paralog ADM, might be closely related to the chronic hypoxic pulmonary hypertension in rats. The disorders of the gene expression and/or the synthesis and metabolism of ADM2/IMD and its receptor CRLR/RAMP1 possibly take part in the pathogenesis of chronic hypoxic pulmonary hypertension in rats.</p>

Changes of intermedin/adrenomedullin 2 and its receptors in the right ventricle of rats with chronic hypoxic pulmonary hypertension / 生理学报

The purpose of the present study was to explore the expression changes of intermedin/adrenomedullin 2 (IMD/ADM2), a novel small molecular bioactive peptide, and its receptors, calcitonin receptor-like receptor (CRLR) and receptor activity modifying proteins (RAMP1, RAMP2, RAMP3) in the right ventricle of rats with chronic hypoxia-induced pulmonary hypertension. Twenty male Sprague-Dawley rats were randomly divided into 4-week hypoxia group and normal control group (each n=10). The rats in hypoxia group were placed in an isobaric hypoxic chamber, in which O(2) content was maintained at 9%-11% by delivering N(2), and CO(2) content was maintained at <3% for 4 weeks (8 h/d, 6 d/week). The rats in the control group were housed in room air. The protein levels of IMD/ADM2 and adrenomedullin (ADM) in blood plasma and right ventricular tissue were measured by radioimmunoassay. The mRNA expressions of IMD/ADM2, ADM and their receptors CRLR, RAMP1, RAMP2, RAMP3 in right ventricular tissue were determined by reverse transcription-polymerase chain reaction (RT-PCR). The results showed that the ratio of right ventricle weight to left ventricle plus septum weight [RV/(LV+S)] and mean pulmonary arterial pressure (mPAP) were higher in hypoxia group than those in the control group (all P<0.01), suggesting that the rat model of pulmonary hypertension was successfully established. However, the mean carotid arterial pressure (mCAP) between the two groups had no significant difference. Compared with that in the control group, ADM contents in plasma and right ventricular tissue in hypoxia group increased by 1.26 and 1.68 folds (all P<0.01), respectively. Likewise, IMD/ADM2 contents in blood plasma and right ventricular tissue in hypoxia group increased by 0.90 and 1.19 folds (P<0.01), respectively, compared with that in the control group. The data of RT-PCR showed that mRNA levels of ADM, IMD/ADM2 and RAMP2 in hypoxia group increased by 155.1% (P<0.01), 80.9% (P<0.01) and 52.9% (P<0.05), respectively, compared with those in the control group. There were no significant differences in mRNA expressions of CRLR, RAMP1 and RAMP3 between the two groups (all P>0.05). Taken together, the results show that the level of IMD/ADM2 increases in the rats with chronic hypoxia-induced pulmonary hypertension.

Effects and relationship between NO and HIF-1alpha in rats with pulmonary hypertension induced by hypoxia / 中国应用生理学杂志

<p><b>AIM</b>To investigate the expression of hypoxia-inducible factor-1 alpha (HIF-1alpha) in rats with chronic pulmonary hypertension induced by hypoxia and hypercapnia and its relationship with nitric oxide(NO).</p><p><b>METHODS</b>Fourty male Sprague-Dawley rats were randomly divided into four groups, normal control group (NC), hypoxia-hypercapnia group (HH), hypoxia - hypercapnia + L-arginine liposome group(HP) and hypoxia-hypercapnia+ N-nitro-L-arginine methylester group (HM). Colorimetric analysis, immunohistochemistry and in situ hybridization were used for detection of NO, HIF-1alpha and constitutive nitric oxide synthase (ecNOS).</p><p><b>RESULTS</b>(1) The mean pulmonary arterial pressure (mPAP) and the weight ratio of right ventricular to left ventricle plus septum (RV/(LV + S)) of HH group were higher than those of NC group (P < 0.05), HP group much lower than HH group (P < 0.01), mPAP of HM higher than HH group ( P < 0.05). 2)0 Contents of NO in plasma and pulmonary tissue homogenates of HH group were much lower than those of NC group (P < 0.01), HP group higher than HH group (P < 0.01). There were no difference between HM group and HH group. (Expression of HIF-1alpha and HIF-1alpha mRNA in pulmonary arterioles of HH group were significantly higher than those of NC group( P < 0.01), HP group lower than HH group (P < 0.01) ,HM group higher than HH group (P < 0.01); Whereas expression of ecNOS and ecNOS mRNA in pulmonary arterioles of HH were lower than those of NC group( P < 0.05, IP group higher than HH group (P < 0.01), HM group lower than HH group (P < 0.05).</p><p><b>CONCLUSION</b>HIF-1alpha is involved in the pathogenesis of chronic pulmonary hypertension induced by hypoxia and hypercapnia. The protective function of NO in the pathogenesis might be partly depended on its effects on the expression/activity of HIF-1alpha in lung.</p>

Expression of Urotensin II and its receptor on right ventricle in rats of pulmonary hypertension / 中国应用生理学杂志

<p><b>AIM</b>To observe the expression of Urotensin II (U II) and its receptor (UT) on right ventricle in rats with chronic pulmonary hypertension induced by hypoxia and hypercapnia.</p><p><b>METHODS</b>Twenty male SD rats were randomly divided into normal control group (NC) and hypoxia-hypercapnia 4-week group(HH). Mean pulmonary arterial pressure(MPAP) and the weight ratio of right ventricle (RV) to left ventricle plus septum (LV+ S) were calculated separately. U II in plasma was measured using radioimmunoassay. The expression of U II was observed in right ventricle myocytes and right ventricle arteries by immunohistochemistry. The expression of U II mRNA and UT mRNA were observed in right ventricle myocytes and right ventricle arteries by in situ hybridization.</p><p><b>RESULTS</b>(1) The MPAP and RV/LV + S of HH group were higher respectively than those of NC group (P < 0.01, respectively). (2) The plasma U II content of HH group did not increased obviously than that of NC group. (3) The expression score of U II, U II mRNA, UT mRNA by right ventricle myocytes in HH group were higher significantly than those of NC group (P < 0.01 respectively). (4) The average value of integral light density (LD) of U II, U II mRNA, UT mRNA by right cardial arteries in HH group were higher significantly than those of NC group (P < 0.01, respectively).</p><p><b>CONCLUSION</b>The expression of U II in right ventricle arteries and right ventricle myocytes increase significantly during the formation of pulmonary hypertension and right ventricle hypertrophy in rats chronically exposed to hypoxia-hypercapnia. These changes indicate that U II might be involved in right ventricle remodeling, which promotes proliferation of cardiac muscle cells.</p>

Dynamic changes of urotensin II receptor in pulmonary artery and arterioles of rats chronically exposed to hypoxia-hypercapnia / 中国应用生理学杂志

<p><b>AIM</b>To investigate the dynamic changes and functions of urotensin II (U lI) receptor (UT) in pulmonary arteries of rats chronically exposed to hypoxia-hypercapnia.</p><p><b>METHODS</b>In rats with hypoxia-hypercapnia at 1, 2 and 4 weeks U II receptor binding of pulmonary arteries sarcolemma was determined by radioligand assay. U II mRNA and UTmRNA in various grades of pulmonary arterioles were measured by in situ hybridization.</p><p><b>RESULTS</b>(1) Mean pulmonary pressure (mPAP) and weight ratio of right ventricle to left ventricle and septum (RV/LV + S) of 1-week group were higher than those of normal control (NC) group by 26.2% and 21.6% (P < 0.01), respectively, and 2-week group higher than 1-week group by 22.5% and 14.1% (respectively, P < 0.01). However, no significant changes were found between 4-week and 2-week group. (2) U Il receptor (Bmax) of 1-week group was higher than NC group by 38.8%, 2-week group higher than 1-week group by 23.2%, and 4-week group increased 7.3% compared with 2-week group (respectively, P < 0.01). The UT changes were time-dependent, while the affinity to U II (Kd) was no different among each group. (3) UII mRNA in each grade of pulmonary arterioles of 2-week group and 4-week group were higher than NC group (respectively, P < 0.01), and those of 2-week group were higher than 1-week group by 5.9% (P > 0.05), 16.4% and 9.1% (respectively, P < 0.01), while no differences existed between 2-week group and 4-week group. (4) UT mRNA in each grade of pulmonary arterioles of all hypoxia-hypercapnia groups was higher than NC group (respectively, P < 0.01), and those of two abaxial grade vessels in 1-week group were the highest. No differences existed between 2-week group and 4-week group. (5) The pulmonary vessels remodeling were time-dependently aggravated by hypoxia-hypercapnia.</p><p><b>CONCLUSION</b>The dynamic changes of UT in pulmonary arterioles might have important contribution to the development of pulmonary hypertension and pulmonary arteriole remodeling induced by chronic hypoxia-hypercapnia in rats.</p>