Objective To explore the anti-inflammatory effects of ambroxol hydrochloride in chronic obstructive pulmonary disease（COPD）.Methods Thirty Wistar rats were randomly divided into three groups，ie.a control group，a smoking group and an ambroxol group.The rats in the smoking and ambroxol groups were exposed to cigarettes smoking for 12 weeks.Ambroxol hydrochloride was administered via intragastric gavage after 4 weeks smoking in the ambroxol group.After 12 weeks，the expiratory airway resistance(Re) and dynamic lung compliance(CLdyn) were measured.The expression levels of nuclear factor kappa B（NF-κB）and intercellular adhesion molecule-1(ICAM-1) in airway epithelium cell were observed by immunohistochemical method.Results Re was increased and CLdyn was decreased significantly in the smoking and ambroxol groups compared with the control group(all Plt;0.01).Re was lower (Plt;0.01) and CLdyn was higher(Plt;0.05) in the ambroxol group than those in the smoking group.B.The level of NF-κB and ICAM-1 in smoking and ambroxol groups were obviously increased compared with the control group (all Plt;0.05)，which was decreased in the ambroxol group compared with the smoking group(both Plt;0.05).C.The expression of NF-κB was positively correlated with ICAM-1 expression in airway epithelial cells（r=0.924，Plt;0.01）.Conclusions Smoking can increase the airway resistance，reduce the lung compliance and increase the expression of NF-κB and ICAM-1 in airway epithelium.Ambroxol hydrochloride can relieve those effects of smoking，which suggested an anti-inflammatory therapeutic role in COPD.
Objective To investigate the effects of high dose ambroxol on patients with acute lung injury（ALI） after liver transplantation.Methods Thirty patients with ALI after liver transplantation were divided randomly into an ambroxol group and a control group.On the base of routine treatment，the patients were treated by intravenous infusion with high dose ambroxol of 15 mg/kg once a day for 7 days in the ambroxol group and with normal saline of same volume in the control group.The arterial blood gas analysis was performed and IL-1，IL-10 and TNF-α were measured before and 1 day，3 day and 7 day after the treatment.Length of stay in ICU were recorded and death rate in one year were followed-up.Results After the 1 days，3 days and 7 days of treatment，PaO2 and PaO2/FiO2 were improved in both groups with more significant improvement in the ambroxol group（Plt;0.05）.Before treatment，no differences of IL-1，IL-10 and TNF-α level were found between the two groups.But the level of IL-1 and TNF-α decreased significantly in the ambroxol group compared with the control group after 1 day treatment，and no differences were found after 3 day and 7 day.The level of IL-10 increased in both groups，but significantly in the ambroxol group after 1 day.The lenght of ICU stay in the ambroxol group was shorter than that in the control group[（8.2±5.6）d vs（11.4±6.5）d，Plt;0.05].Two died in the ambroxol group and 3 in the control group with no significant difference.Conclusion High dose ambroxol can improve blood gas exchange and decrease the lenght of ICU stay in ALI patients after liver transplantation，through its inhibitory effects on inflammatory response by down-regulation of IL-1，TNF-α and up-regulation of IL-10.
Objective To observe the protective effects of ambroxol hydrochloride ( AMB) on rabbit model of acute lung injury ( ALI) induced by oleic acid and explore its mechanisms. Methods The ALI model of rabbit was induced by oleic acid. Twenty-four Japanese white rabbits were divided into three groups randomly, ie. a normal saline group ( NC group) , an ALI group and an ALI plus ambroxol injection group ( AMB group) . The pathological changes and apoptotic index ( AI) in lung tissue, Caspase-3 activity in lung tissue homogenate were observed 6 hours after the intervention. Serum activity of superoxide dismutase ( SOD) and serum levels of malonaldehyde ( MDA) , interleukin-1β( IL-1β) , and tumor necrosis factor-α ( TNF-α) were measured simutanously. Results The pathological injury of lung in the AMB group was milder than that in the ALI group. Both the AI in lung tissue and Caspase-3 activity in homogenate in the AMB group were lower than those in the ALI group significantly ( P lt;0. 01, P lt;0. 05 respectively) , butwere higher than those in the NC group( both P lt; 0. 01) . The activity of SOD in serum measured 6 hours after AMB intervention was higher while the serum levels of MDA, IL-1βand TNF-αin serum were lower ( P lt;0. 01) than those in the ALI group significantly ( all P lt;0. 01) . Conclusions Ambroxol hydrochloride has protective effects on oleic acid-induced acute lung injury. The mechanisms may be related to inhibition of oxidative stress and suppression of cytokines synthesis ( IL-1βand TNF-α) , the activity of the Caspase-3,and the apoptosis of lung tissue.
Objective To assess the efficacy of ambroxol on acute lung injury/acute respiratory distress syndrome ( ALI/ARDS) . Methods The randomized controlled study involving ambroxol on ALI/ARDS were searched and identified from Cochrane Library, PubMed, China Academic Journals Full-text Database, Chinese Biomedical Literature Database, WanFang Resource Database, and Chinese Journal Fulltext Database. The quality of the chosen randomized controlled studies was evaluated, and then the valid data was extracted for meta-analysis. Results Ten articles were included, all in Chinese, including 459 cases ofpatients ( 233 cases in experimental group,226 cases in control group) , with baseline comparability between the various experiments. Systematic review showed that in ALI/ARDS patients, high-dose ambroxol was in favor to improve PaO2 [ WMD =12. 23, 95% ( 9. 62, 14. 84) , P lt; 0. 0001] and PaO2 /FiO2 [ WMD = 32. 75,95% ( 30. 00, 35. 51) , P lt;0. 0001] , reduce lung injury score [ WMD = - 0. 49, 95% ( - 0. 66, - 0. 33) ,P lt;0. 0001] , decrease the duration of mechanical ventilation [ WMD = - 2. 70, 95% ( - 3. 24, - 1. 12) ,P lt;0. 0001] and the length of ICU stay [ WMD= - 2. 70, 95% ( - 3. 37, - 2. 04) , P lt;0. 0001] , and lower mortality [ OR=0. 46,95%( 0. 22, 1. 00) , P = 0. 05] . Conclusions The existing clinical evidence shows that, compared with conventional therapy, high-dose ambroxol plus can significantly improve PaO2 , PaO2 /FiO2 , lung injury score, duration of mechanical ventilation, length of ICU stay and mortality in ALI/ARDS patients. Due to the quality of research and the limitations of the study sample, there likely to exist a bias,and may affect the strength of result, so we expect more high-quality, large-scale randomized controlled clinical trial to verify.
Objective To observe the effects of ambroxol injection on mucosal surface structure of trachea injured by intratracheal instillation of amikacin. Methods 280 Wistar rats were randomly divided into four groups( n = 70 in each group) , ie. a normal control group, a normal saline group( intratracheally instilled normal saline) , an amikacin group ( intratracheally instilled amikacin) , and an ambroxol group ( intratracheally instilled amikacin and ambroxol simultaneously) . At the time points of 2, 12, 24, 48, 72 hours six animals in each group were killed and the samples of 1/3 lower segment of trachea were collected and observed by scanning electron microscope. Endotracheal intubation were made on other 6 animals to collecte broncho-alveolar lavage fluid ( BALF) for leucocyte count. Results Compared with the normal control group, elevated leucocyte count was observed in all other groups, various grades of swelling of the cilia were revealed, followed by more or less cilia laid flat with adjacent cilia conglutinated. Then partial cell membrane on top of some cilia bulged out. In terms of injury, the normal saline group was the most mild, and the amikacin group was most serious with the highest leucocyte count. All the parameters were relieved in ambroxol group. Conclusions Intratracheal instillation of amikacin causes acute injury of the ultrastructure of mucosal surface cilia. Ambroxol can promote the recovery process and alleviate inflammation of airway.
Objective To systematically review the efficacy of ambroxol for lung protection in perioperative period. Methods We followed the Cochrane Collaboration methodology to conduct systematic reviews. We searched relevant randomized controlled trials (RCTs) from The Cochrane Library, PubMed, Embase, CBM, CNKI and VIP. We assessed the methodological quality for each outcome by grading the quality, and used RevMan5.0.0 to perform meta-analysis. Results Eight RCTs were eligible and included 669 patients. All of these trials used randomization but the quality scales were B. Compared to the control group, the ambroxol group had a statistically significant benefit in atelectasis, pulmonary complications, cough and expectoration degree. The RR (95%CI) were 0.44 (0.25, 0.78), 0.51 (0.34, 0.75), 0.39 (0.16, 0.94) and 0.22 (0.09, 0.53), respectively. The ambroxol group was also better than the control group in sputum volume, sputum characteristics, rales and pulmonary surfactant. Conclusion Ambroxol can improve respiratory system symptoms post-operatively, reduce pulmonary complications, and prevent pulmonary surfactant from decreasing during operation. Ambroxol has a satisfactory lung protective effect in the preoperative period, but we can’t define a proper dose and usage time.
Objective To evaluate the efficacy and safety of domestic ambroxol hydrochloride injection in the treatment of lower respiratory tract infection. Methods A total of 120 patients with respiratory tract infections were included and randomized into the treatment group (ambroxol hydrochloride injection 30mg, iv, q12h) and the control group (mucosolvan ampoule 30mg, iv, q12h). The duration of treatment was 6 days. Results 118 patients completed the trial, 59 in each group. From Day 1 to Day 6, the severity scores of cough, sputum amount, difficulty in expectoration and rales were similar between the two groups (Pgt;0.05), but a significant difference was observed in the nature of sputum (Plt;0.05). The total effective rates of the treatment group and the control group were 96.6% (FAS analysis and PP analysis) or 93.3% (FAS analysis), and 94.9% (PP analysis), respectively. There was no significant difference between the two groups (Pgt;0.05). The incidence of adverse effects was comparable between the two groups (1.7% vs. 0%, Pgt;0.05), and no severe adverse effect was observed. Conclusion The efficacy of domestic ambroxol hydrochloride injection in the treatment of lower respiratory infection was equal to that of mucosolvan ampoule, and it can even further improve the nature of sputum. Ambroxol hydrochloride was as safe as mucosolvan ampoule.
Objective To assess the effectiveness and safety of an aerosol inhalation of ambroxol in accessory treatment of pneumonia. Methods Biomedical databases, including MEDLINE, EMbase, The Cochrane Central Register of Controlled Trials (CENTRAL), CBM-disk and CNKI were searched. Randomized controlled trials (RCTs) and quasi-RCTs that compare aerosol inhalation of ambroxol with placebo or other aerosol inhalation regimens were collected. A critical quality assessment and Meta-analysis were performed for included studies. Results Thirteen RCTs were included and all of them were carried out in China. None of the trials described the method of randomization, allocation concealment, blind, and follow-up. With Juni scales, 13 trials scored C degree. Compared with the control group, aerosol inhalation of ambroxol improved total improvement rate and symptoms, and shortened hospital stay. Although statistical difference was not found in some comparisons, all trials showed beneficial tendency. We didn’t find any RCTs describing the safety of ambroxol aerosol inhalation. Conclusion Because of the low quality of RCTs on ambroxol aerosol inhalation for pneumonia, no reliable conclusion can be drawn from our Meta-analysis. Well-designed RCTs and economic evaluation are urgently needed to evaluate the value and safety of aerosol inhalation of ambroxol in treating pneumonia.
Objective To investigate the effects of ambroxol hydrochloride on surface structure of trachea mucosa in rats injured by intratracheally instilled amikacin. Methods Thirty Wistar rats injured by intratracheally instilled amikacin ( 0. 252 mL/kg) were randomly divided into a control group ( n =15) and an ambroxol group ( n= 15) . The rats in the ambroxol group were intraperitoneally injected with ambroxol hydrochloride ( 70 mg/kg) 5 minutes after amikacin administration. They were all equally divided into five subgroups and sacrificed at 2, 4, 8, 28, 48 hours respectively. Then the samples of 1/3 lower segment of trachea were collected and observed under scanning electron microscope. Results In the control group, the mucous secretion and its stickness were increased. The cilia were found lodged, sticked together, aligned abnormally, abrupt partly, and recovered slowly, with the percentage of damaged area of 98. 2% , 98. 5% , 97. 5%, 92. 7% , 82. 1% at 2, 4, 8,24,48 h, respectively. The injuries of mucosa in the ambroxol group were much milder and recovered more rapidly than those in the control group, with the percentage of damaged area of 85. 7% , 81. 9% , 73. 0% , 61. 9% , 50. 2% at 2, 4, 8, 24, 48 h, respectively. Conclusions Intratracheal instillation of amikacin can cause cilia ultrastructure damage on tracheal mucosa. Ambroxol can promote the recovery process and alleviate airway inflammation.
ObjectiveTo explore the effect of respiratory support in Community Respiratory Support Center on patients with chronic obstructive pulmonary disease (COPD) in stable phase. MethodsSixty-four GOLD gradeⅢpatients with stable COPD over age of 55 years were randomly divided into two groups.A respiratory support group received respiratory support in Community Respiratory Support Center, including health education, long-term oxygen therapy (LTOT), long-term ambroxol for atomization, long-term budesonide and formoterol for inhalation.A control group were prescribed budesonide and formoterol for inhalation when recruited, informed LTOT and long-term ambroxol for atomization at home, and follow-up visits to clinic every month. ResultsAfter 24 months of treatment in the respiratory support group, SpO2, PaO2, FEV1%pred, 6MWD, BMI, and ALB increased, mMRC, CAT, Hb, PaCO2 decreased (P < 0.05).While in the control group, FEV1%pred decreased, mMRC and CAT increased (P < 0.05), other indexes did not change significantly (P > 0.05).The times of acute exacerbation and hospitalization of the respiratory support group was less than that in the control group(P < 0.05). ConclusionsEstablishing Community Respiratory Support Center will benefit patients with stable COPD correct hypoxemia, slow the deterioration of lung function, improve the nutritional status of patients, and can also increase patients compliance to treatment.