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 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 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 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 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 retrospectively analyze off-label drug use (OLDU) situation of ambroxol hydrochloride injection (AHI) among inpatients in the Guangdong General Hospital in 2012, so as to provide references for AHI OLDU. MethodsAll medical orders of AHI for inpatients in the Guangdong General Hospital in 2012 were included, and OLDU was judged according to drug labels. We summarized situation of drug use in all departments, analyzed OLDU incidence in administration path and in dose, calculated prescribed daily dose (PDD) and utilization index (DUI) in each department to evaluate the degree of OLDU in dose. Resultsa) A total of inpatients 138 227 patient-days who used AHI were included. OLDU occurred in all departments in this hospital and the total OLDU incidence was 67.06%. b) OLDU in dose occurred in 71.43% of the departments (25/35) with an incidence of 29.53%; the top 4 departments were cardiac surgery intensive care unit department (CICU) (97.74%), cardiac surgery department (97.51%), pediatric cardiac surgery department (72.30%) and pediatric intensive care unit department (PICU) (70.28%) in order. c) The PDDs in CICU department, cardiac surgery department, PICU departments, pediatric cardiac surgery department, oncological surgery ward, neurosurgery ward and intensive care unit (ICU) were higher than the defined daily dose (DDD), of which, the DUI/cDUI in CICU, cardiac surgery department, PICU and pediatric cardiac surgery department were 1 to 3 times higher than normal level. d) No relevant adverse drug reaction/adverse event (ADR/AE) reports were received in this hospital in 2012. ConclusionAHI is widely used in the Guangdong General Hospital, and AHI OLDU is commonly-seen. Further studies should be conducted to analyze the influence factors of AHI OLDU in dose and to evaluate the rationality of its application.
ObjectiveTo investigate the effect of ambroxol hydrochloride on c-Jun N-terminal kinase (JNK) signal pathway in gastric aspiration lung injury. MethodsForty healthy male Sprague Dawley rats were randomly divided into a control group, an injury group, a SP600125 (JNK specific inhibitor) group and an ambroxol group. The model of gastric aspiration lung injury was established by aspiration of gastric contents. The rats in the SP600125 group preoperatively received intravenous injection of JNK specific inhibitor SP600125 (3 mg/100 g). The rats in the ambroxol group received intravenous injection of ambroxol hydrochloride (50 mg/kg) 2 hours after the damage occurred. The neutrophil count and malondialdehyde (MDA) activity in bronchoalveolar lavage fluid (BALF), the lung wet weight/dry weight ratio (W/D), and myeloperoxidase (MPO) activity were measured. The protein expressions of JNK and phosphorylated JNK (p-JNK) and inducible nitric oxide synthase (iNOS) in lung tissue were detected by Western blot method. The changes of lung tissue structure were observed under light microscope. ResultsIn the injury group, the neutrophil counts and MDA activity in BALF, W/D, MPO activity, p-JNK and iNOS protein expression increased significantly, lung tissue appeared obvious histopathological injury compared with the control group. In the SP600125 group and the ambroxol group, neutrophil count and MDA activity in BALF, lung W/D, MPO activity, p-JNK and iNOS protein expression were significantly decreased compared with the injury group (P < 0.05), and the damage of the lung tissue pathology was reduced. The expression of JNK protein in lung tissue was not different in all groups (P > 0.05). ConclusionsJNK is involved in inflammatory reaction of gastric aspiration lung injury. The protective effect of ambroxol may be related to the inhibition of JNK signaling pathway and the inhibition of iNOS expression.
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.
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.
ObjectiveTo observe the effects of cluster therapy combined with anisodamine, dexamethasone and ambroxol on arterial blood gas, inflammatory cytokines and pulmonary pathological changes by making an early (<48 h) primary blast lung injury model in rats. MethodsEighty Wistar rats were randomly divided into six groups, ie. a control group (n=5), an injury group (n=15), an ambroxol treatment group (n=15), a dexamethasone treatment group, a scopolamine treatment group (n=15), a combination of ambroxol, dexamethasone and anisodamine group (n=15). The treatment groups were injected intraperitoneally with ambroxol 46.7 mg/kg (three times a day) or (and) dexamethasone at 5 mg·kg–1·d–1 or (and) anisodamine at a dose of 3.33 mg/kg (three times a day). The rats in the injury group were injected intraperitoneally with an equal volume of normal saline. Respiratory rate and weight change were observed before and after injury. Five rats were sacrificed at 6 hours, 24 hours and 48 hours after injury in each experimental group. Arterial blood gas analysis, Yelverton pathological score, lung tissue wet/dry weight ratio, serum tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were measured. The lung histopathology was observed. ResultsAfter lung blast injury, the rats in the injury group showed progressive respiratory acidosis, and hypoxemia increased with the increase of IL-6 and TNF-α in a time-dependent manner. The PaO2 decreased in the groups with ambroxol, dexamethasone and anisodamine alone or in combination with anisodamine, and the contents of serum IL-6 and TNF-α decreased. Pathological edema and inflammatory infiltration of lung tissue were alleviated significantly. ConclusionsAfter treatment with dexamethasone, anisodamine and ambroxol after lung blast injury, blood gas analysis is improved, inflammatory factor level is decreased and lung injury is alleviated, indicating that the three drugs can treat lung detonation injury in rats. The cluster therapy is superior to the single drug therapy.