Effects of N-Acetylcysteine combined with Ambroxol Hydrochloride on clinical symptoms, CRP, and PCT in children with pneumonia.

OBJECTIVE: This study investigated the effects of N-Acetylcysteine (NAC) combined with Ambroxol Hydrochloride (AH) on clinical symptoms, C-Reactive Protein (CRP), and Procalcitonin (PCT) levels in children with pneumonia. METHODS: A total of 98 children with pneumonia were assigned to the control group and observation group by random number table method. NAC was administered to the observation group and AH was given to the control group. The therapeutic effect was observed, the disappearance time of clinical symptoms and levels of inflammatory factors, lung function parameters, blood gas analysis parameters, and immunoglobulin were measured. The incidence of adverse reactions was statistically analyzed. RESULTS: A higher effective rate was observed in the observation group than in the control group (p < 0.05). Antipyretic time, cough disappearance time, and lung rale disappearance time in the observation group were shorter than those in the control group (p < 0.05). After treatment, CRP and PCT were lower (p < 0.05), FVC, FEV1, and FEV1/FVC were higher, PaCO2 was lower, PaO2 and SaO2 were higher, and IgA, IgG, IgM, and C3 were higher in the observation group than those in the control group (p < 0.05). The incidence of adverse reactions between the two groups was not significantly different (p > 0.05). CONCLUSION: NAC combined with AH is effective in the treatment of pediatric pneumonia by effectively alleviating clinical symptoms, reducing inflammatory factors, and improving lung function and immune function.

Pulmonary-Affinity Paclitaxel Polymer Micelles in Response to Biological Functions of Ambroxol Enhance Therapeutic Effect on Lung Cancer.

PURPOSE: Cancer chemotherapy effect has been largely limited by cell autophagy and little drug accumulation at the action sites. Herein, we designed an intelligent strategy involving paclitaxel (PTX) polymer micelles in response to biological functions of ambroxol (Ax). The amphiphilic polymers polyethyleneglycol-polylactic acid (PEG-PLA) and Pluronic P105 were selected as nanocarriers to encapsulate PTX to form into lung affinity PEG-PLA/P105/PTX micelles. Ax which can up-regulate the secretion of pulmonary surfactant (PS) and inhibit autophagy was hired to change the microenvironment of the lung, thereby promoting the lung accumulation and increasing cell-killing sensitivity of the micelles. METHODS: The physical and chemical properties of the micelles were characterized including size, morphology, critical micellar concentration (CMC) and in vitro drug release behavior. The therapeutic effects of the combination regimen were characterized both in vitro and in vivo including study on Ax in promoting the secretion of pulmonary surfactant, in vitro cytotoxicity, cellular uptake, Western blotting, in vivo biodistribution, in vivo pharmacokinetics and in vivo antitumor efficacy. RESULTS: The PEG-PLA/P105/PTX micelles showed a particle size of 16.7 ± 0.5 nm, a nearly round shape, small CMC and sustained drug release property. Moreover, the in vitro results indicated that Ax could increase PS and LC3 protein secretion and enhance the cytotoxicity of PEG-PLA/P105/PTX micelles toward A549 cells. The in vivo results indicated that the combination therapeutic regimen could promote the micelles to distribute in lung and enhance the therapeutic effect on lung cancer. CONCLUSION: This multifunctional approach of modulating the tumor microenvironment to enhance drug transportation and cell-killing sensitivity in the action sites might offer a new avenue for effective lung cancer treatment.

The therapeutic efficacy of high-dose ambroxol and the nursing effects in the treatment of severe pneumonia.

To observe and analyze the therapeutic efficacy of high-dose ambroxol in the treatment of severe pneumonia, as well as summarize the nursing methods. A total of 180 patients diagnosed with severe pneumonia and treated at our hospital who were enrolled. The patients were divided into a control group and are search group, with 90 patients in each group. Of those, patients in the research group were treated with high-doses ambroxol, while small-dose ambroxol was administered to patients in the control group. The therapeutic efficacy was compared between both groups. Meanwhile, predictive nursing regimens were applied on patients in the research group, while routine nursing care was given to patients in the control group. The nursing satisfaction was compared between both groups. By comparing the pulmonary function indicators, Comparison of procalcitonin (PCT) and C-reactive protein (CRP) results showed that all indicators of the research group were obviously better than those of the control group (p<0.05). The time of infection control, ICU stay and hospital stay of the research group were significantly less than those of the control group (p<0.05). Moreover, the overall nursing satisfaction of the research group was significantly higher than that of the control group (p<0.05).Application of high-dose ambroxol and scientific nursing methods could significantly improve the therapeutic efficacy in the treatment of severe pneumonia and gain favorable nursing satisfaction.

Mucoactive agents for adults with acute lung conditions: A systematic review.

BACKGROUND AND OBJECTIVES: Inhaled mucoactive agents are used to enhance airway clearance, however efficacy and safety are unclear in adults with acute respiratory conditions. METHODS: We systematically reviewed randomized controlled trials assessing respiratory function; safety; length of stay (LOS); mucus; radiology; and oxygenation. RESULTS: No adverse events were reported for dornase alfa (n = 63), N-acetylcysteine (NAC, n = 50), ambroxol (n = 140), hypertonic saline (n = 33), heparin (n = 384), mannitol (n = 20) or isotonic saline. During invasive ventilation, NAC, dornase alfa and saline had no effect on mucus. Postoperatively, mucus characteristics improved with NAC (n = 10). Ambroxol lowered LOS (mean difference 4 days) and halved complications following lung carcinoma resection (n = 140). Heparin improved ventilator-free days (n = 130, mean difference 3.9-4.6) and intensive care LOS (n = 223, 3.2 days), but not ventilator-acquired pneumonia. CONCLUSION: Dornase alfa, hypertonic saline and NAC were ineffective for atelectasis/mucus plugging while intubated. More data are required to support using NAC, ambroxol and heparin during acute illness.

[Clinical study of the oxygen drive aerosol inhalation with budesonide and ambroxol in the prevention of adult post-thoracotomy pneumonia].

OBJECTIVE: To study the clinical effect of the oxygen drive aerosol in halation with budesonide and ambroxol in the prevention of adult post-thoracotomy pneumonia. METHODS: This was a randomized, open and parallel controlled trial. We chose 80 cases of patients in the department of thoracic surgery in the First Affiliated Hospital of Xi'an Jiaotong University which fitted our criteria as the research object. The selected patients were randomly divided into the active group and the control group, and the active group underwent oxygen drive aerosol inhalation (2 mg budesonide combined 60 mg ambroxol) for 3 days before operation, and the control group without preoperative aerosol inhalation, and their postoperative therapy was the same. RESULTS: The baseline data showed that the differences in sex, age, disease and smoking were not statistically significant between the two groups, P>0.05. The results of blood gas analysis before 12 hours of operation suggested that, the PaO2and PaCO2values of the active group were (88.40±9.40) mmHg and (38.30±6.10) mmHg; The PaO2and PaCO2 values of the control group were (85.09±7.18) mmHg and (41.21±3.15) mmHg. And the two groups' P values were 0.029 and 0.011, with statistical differences. There were 3 patients who developed postoperative pneumonia out of 40 patients in the active group, the incidence was 7.50%, but the incidence of control group was 25.00%. The P value was 0.034, with statistical differences. We also analyzed the influence of different diseases and surgical methods on postoperative pneumonia, and the results showed that in the active group and the control group, the incidence of postoperative pneumonia in the patients with esophageal cancer was lower than that in lung cancer patients, and there was a statistically significant difference (P<0.05). In the active group, the numbers of pulmonary deed resection, lobectomy and pulmonary sleeve resection were 2, 21 and 1 cases respectively, and the corresponding numbers in the control group were 2, 21 and 2. Among the two groups, the incidence of postoperative pneumonia in the patients with different surgical methods of lung cancer was statistically significant (P<0.05). CONCLUSION: If we implement respiratory preparation with budesonide plus ambroxol inhalation for 3 days before operation, we can greatly reduce the incidence of postoperative pneumonia?

Antenatal maternal medication administration in preventing respiratory distress syndrome of premature infants: A network meta-analysis.

INTRODUCTION: High incidence of respiratory distress syndrome (RDS) was revealed in preterm infants, which acted as one of the main factors that led to infant death. OBJECTIVES: This network meta-analysis (NMA) was performed to rank the efficacy of different therapies in preventing for premature infants. METHODS: PubMed, Embase, Cochrane Library, CINAHL, and CNKI were searched. Statistical analysis was performed using STATA statistical software (Version 12.0). Odds ratios (ORs) with 95% credible intervals (95%CrIs) were applied to evaluate relative efficacy of various treatments. Ranking of probabilities of each treatment was illustrated by surface under the cumulative ranking curve (SUCRA). Consistency between direct and indirect evidence was assessed using the node-splitting plots and heat plots. RESULTS AND CONCLUSION: A total of 48 trials were eligible to evaluate the efficacy of 3 interventions including ambroxol (AMB), betamethasone (BET), and dexamethasone (DEX). Three outcomes including the incidence of RDS, bronchopulmonary dysplasia (BPD) and neonatal death were assessed. Compared with placebo, BET, DEX, and AMB all demonstrated better efficacy in terms of preventing RDS and neonatal death. No significant difference among treatments was found in the assessment of the incidence of BPD. According to SUCRA, AMB was the optimal treatment in preventing RDS and neonatal death. Besides, no significant inconsistency was detected between direct and indirect evidence. To conclude, no significant difference was found among these three medications. AMB seems to have the potential to be the most effective treatment for reducing the incidence of RDS and neonatal death.

Time-shifted co-administration of sub-analgesic doses of ambroxol and pregabalin attenuates oxaliplatin-induced cold allodynia in mice.

BACKGROUND: Oxaliplatin-induced cold allodynia is a frequent complication appearing in patients treated with this anti-tumor drug. Since, there are no clear algorithms to overcome this painful condition effectively, it is important to establish novel strategies for its treatment. AIM: In this study, the ability of pregabalin and ambroxol, used as single drugs or in combinations administered in a time-shifted manner to attenuate cold allodynia was assessed in the mouse cold plate test. The hot plate test was additionally used to assess antinociceptive properties of ambroxol in the acute, thermally-induced pain model. Locomotor activity and motor coordination of mice were also evaluated. In silico studies were undertaken to predict potential binding of ambroxol to sodium channel (Nav) subtypes whose overexpression is implicated in the development of oxaliplatin-induced neuropathic pain. KEY FINDINGS: A hyperadditive antiallodynic effect of combined sub-analgesic ambroxol and pregabalin was demonstrated in oxaliplatin-treated mice. This effect was particularly strong when these drugs were given 4 h apart. Both drugs used in combination reduced animals' locomotor activity, but they did not impair motor coordination in the rotarod test. Ambroxol did not show antinociceptive properties in the hot plate test. The molecular docking studies predicted that in mice ambroxol might bind to Nav1.6 and Nav1.9 rather than Nav1.7 and Nav1.8. SIGNIFICANCE: Time-shifted co-administration of sub-analgesic doses of ambroxol and pregabalin effectively attenuates oxaliplatin-induced cold allodynia. Molecular docking model predicts preferential binding of ambroxol to mouse Nav1.6, Nav1.9 channels. This mechanism, if confirmed in vitro, might explain pharmacological activities observed in vivo.

Clinical research on airway intervention before tracheal extubation after general anesthesia on snoring children.

OBJECTIVE: To analyze the method and the effect of airway intervention before tracheal extubation in post-anesthesia cure unit (PACU) after anesthesia when removing the tonsil under general anesthesia and adenoidectomy under nasal endoscope on children with snoring. PATIENTS AND METHODS: 46 cases diagnosed as snoring were executively selected in this study. The cases were randomly divided into the control group (n = 22) and the observation group (n = 24). For airway intervention after general anesthesia during the recovery period, the control group was treated with intravenous injection of 0.5 µg/kg remifentanil, whereas the observation group was treated with atomization inhalation of 15 mg ambroxol hydrochloride and 0.5 mg budesonide suspension. RESULTS: The clinical effects of both methods were compared and analyzed for statistical analysis. The blood pressure, heart rate and blood oxygen saturation at 30 min and 10 min after extubation in the control group was significantly more stable than those in the observation group (p < 0.05). The alertness/sedation (OAA/S) score in the observation group was significantly higher than that in the control group (p < 0.05). The prevalence rate of complications after extubation in the two groups was not statistically significant (p > 0.05). The levels of serum cortisol (Cor) and IL-8 in the control group were significantly lower than those in the observation group (p < 0.05). CONCLUSIONS: Both methods are effective for treatment of airway intervention concerned with snoring children after general anesthesia during the recovery period. The effect of remifentanil on hemodynamics is relatively huge compared with that of atomization inhalation.

Correlation Between Tumor Necrosis Factor-α and Interleukin-1ß in Exhaled Breath Condensate and Pulmonary Function.

BACKGROUND: Exhaled breath condensate (EBC) has emerged as a noninvasive method for assessing inflammation in lung diseases. Our aim is to investigate the correlation between tumor necrosis factor α (TNF-α) and interleukin 1ß (IL-1ß) in EBC and in lung tissue, and between these values in EBC with pulmonary function tests in patients with chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS: To ensure the availability of lung tissue, 60 patients undergoing resection for early lung cancer were divided into 3 groups: a COPD treatment group, a COPD control group and a non-COPD group. Patients in the COPD treatment group received what was termed "lung-protective treatment" including ambroxol, budesonide and ipratropium bromide in addition to chest physiotherapy. Patients underwent pulmonary function testing and EBC collection, and TNF-α and IL-1ß were detected by enzyme-linked immunosorbent assay (ELISA). TNF-α and IL-1ß in lung tissues were evaluated by immunoflorescense. Correlations were analyzed by Pearson correlation coefficients. RESULTS: The TNF-α and IL-1ß levels in EBC were significantly higher in the COPD groups compared with the non-COPD group before surgery (all P < 0.01), and the levels were significantly decreased after lung-protective treatment was received before surgery (all P < 0.01). TNF-α and IL-1ß levels in EBC were significantly decreased in all patients after surgery with lung-protective treatment (P = 0.027, P = 0.004). TNF-α and IL-1ß content in lung tissues was significantly higher in the COPD groups (all P < 0.05), and the histologic analysis showed similar results. Negative correlations between FEV1/FVC and expression of TNF-α and IL-1ß were observed. There was a positive correlation between TNF-α and IL-1ß in lung tissues and in EBC. CONCLUSIONS: TNF-α and IL-1ß in EBC are potential biomarkers for evaluating pulmonary function and inflammation in patients with COPD. Furthermore, lung-protective treatment is effective in reducing inflammation in patients with COPD.

Ambroxol inhalation ameliorates LPS-induced airway inflammation and mucus secretion through the extracellular signal-regulated kinase 1/2 signaling pathway.

Ambroxol, a metabolite of bromhexine, is shown to exert several pharmacological activities, including secretolytic, anti-inflammatory and antioxidant actions. Oral and intravenous administration of ambroxol is useful for the airway inflammatory diseases. However, little is known about its potential in inhalation therapy for lipopolysaccharide (LPS)-induced mucous hypersecretion and inflammatory response. In the present study, we compared the pharmacological effects of ambroxol by inhalation with intravenous administration and preliminarily explored its mechanism of action. Our results demonstrated that ambroxol administered by inhalation inhibited MUC5AC expression, reduced glycosaminoglycan levels, enhanced the function of mucociliary clearance and promoted sputum excretion, suggesting that ambroxol increases expectoration of sputum by reducing its viscosity. Moreover, ambroxol significantly alleviated LPS-induced the influx of inflammatory cells and the extracellular signal-regulated kinase 1/2 (Erk 1/2) expression in lung tissues, and inhibited increases in the mRNA expression of the pro-inflammatory cytokines tumor necrosis factor (TNF)-α, CCL-2 (monocyte chemotactic protein-1), KC (keratinocyte cell protein) and interleukin (IL)-1ß in lung tissues. The secretolytic and anti-inflammatory effects of inhaled ambroxol at a dose of 7.5 mg/ml was comparable to that of ambroxol at 20 mg/ml i.v. and dexamethasone at 0.5 mg/kg i.p. In addition, we found that ambroxol dose-dependently inhibited LPS-induced increases in the mRNA expression of MUC5AC, TNF-α, and IL-1ß in human bronchial epithelial cell (NCI-H292) by inhibiting the Erk signaling pathway. These results demonstrate the beneficial effects of ambroxol in inhalation therapy for the airway inflammatory diseases.

Effects of ambroxol hydrochloride on concentrations of paclitaxel and carboplatin in lung cancer patients at different administration times.

Our previous preliminary study revealed a synergistic effect of ambroxol hydrochloride with chemotherapeutic agents such as paclitaxel and carboplatin in lung cancer. However, the optimal conditions such as administration time and drug concentration of ambroxol hydrochloride to achieve the maximum synergistic effect remained unclear. Therefore, concentration changes of the chemotherapy drugs paclitaxel and carboplatin in the sputum were observed after ambroxol hydrochloride administration at different times in order to determine the most effective time frame of ambroxol hydrochloride administration. In this study, 470 cases of non-small cell lung cancer (NSCLC) were divided into different groups with ambroxol hydrochloride administered at different time points prior to chemotherapy, while another 171 cases received no ambroxol hydrochloride prior to chemotherapy. The results showed the concentrations of paclitaxel and carboplatin in sputum of patients treated with ambroxol hydrochloride were significantly higher than those of the control group, suggesting that ambroxol hydrochloride significantly increased the local concentrations of chemotherapeutic agents in lung tissues of NSCLC. Furthermore, the intravenous administration of ambroxol hydrochloride more than 48 hours before chemotherapy showed an optimized schedule and much greater efficacy in increasing drug concentrations than that of the control group. No statistical differences were found in the rates of grade 2 or above myelosuppression between the ambroxol intervention and control groups. Taken together, these results demonstrate that ambroxol hydrochloride administered intravenously more than 48 hours prior to chemotherapy optimally increased the concentrations of paclitaxel and carboplatin in lung tissue without significantly increasing hematologic toxicity.

Meta-analysis of high doses of ambroxol treatment for acute lung injury/acute respiratory distress syndrome based on randomized controlled trials.

This study seeks to evaluate the potential benefits of high doses of ambroxol treatment for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) by conducting a meta-analysis based on randomized controlled trials (RCTs). We searched the Pubmed, Embase, China National Knowledge Infrastructure, and Wanfang databases through December 2013. Only RCTs evaluating high doses of ambroxol (≥15 mg/kg or 1000 mg/day) treatment for patients with ALI/ARDS were selected. We included 10 RCTs involving 508 patients. Adjuvant treatment with high doses of ambroxol increased PaO(2)/FiO(2) (weight mean differences [WMD] = 69.18, 95% confidence intervals [CI]: 41.71-96.65), PO(2) (WMD = 11.74, 95% CI: 8.50-14.99), and SaO(2) (WMD = 2.15, 95% CI: 1.60-2.71) compared with usual treatment. Treatment with high doses of ambroxol appeared to reduce serum tumor necrosis factor-α level (WMD -7.92 µg/L; 95% CI, -10.94 to -4.9) and interleukin-6 level (WMD = -20.65 µg/L, 95% CI: -24.74 to -16.55) and to increase serum superoxide dismutase level (WMD = 19.07 NU/mL, 95% CI: 6.16-31.97). The findings suggest that treatment with high doses of ambroxol appears to improve PaO(2)/FiO(2), PO(2), and SaO(2), and the benefits might be related to ambroxol's anti-oxidant and anti-inflammatory properties.

Nebulized and oral thiol derivatives for pulmonary disease in cystic fibrosis.

BACKGROUND: Cystic fibrosis is an inherited condition resulting in thickened, sticky respiratory secretions. Respiratory failure, due to recurrent pulmonary infection and inflammation, is the most common cause of mortality. Muco-active therapies (e.g. dornase alfa and nebulized hypertonic saline) may decrease sputum viscosity, increase airway clearance of sputum, reduce infection and inflammation and improve lung function. Thiol derivatives, either oral or nebulized, have shown benefit in other respiratory diseases. Their mode of action is likely to differ according to the route of administration. There are several thiol derivatives, and it is unclear which of these may be beneficial in cystic fibrosis. OBJECTIVES: To evaluate the efficacy and safety of nebulized and oral thiol derivatives in people with cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, comprising references identified from comprehensive electronic database searches, hand searches of relevant journals, abstract books and conference proceedings.Most recent search: 13 June 2013.We also conducted a PubMed search on 26 February 2013 for relevant published articles. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing nebulized or oral thiol derivatives to placebo or another thiol derivative in people with cystic fibrosis. DATA COLLECTION AND ANALYSIS: The authors independently assessed trials for inclusion, analysed risk of bias and extracted data. MAIN RESULTS: Searches identified 23 trials; nine trials (255 participants) are included, of these seven trials are more than 10 years old. Three trials of nebulized thiol derivatives were identified (one compared 20% N-acetylcysteine to 2% N-acetylcysteine; another compared sodium-2-mercaptoethane sulphonate to 7% hypertonic saline; and another compared glutathione to 4% hypertonic saline). Although generally well-tolerated with no significant adverse effects, there was no evidence of significant clinical benefit in our primary outcomes in participants receiving these treatments.Six trials of oral thiol derivatives were identified. Three trials compared N-acetylcysteine to placebo; one compared N-acetylcysteine, ambroxol and placebo; one compared carbocysteine to ambroxol; and one compared low and high-dose N-acetylcysteine. Oral thiol derivatives were generally well-tolerated with no significant adverse effects, however there was no evidence of significant clinical benefit in our primary outcomes in participants receiving these treatments. AUTHORS' CONCLUSIONS: We found no evidence to recommend the use of either nebulized or oral thiol derivatives in people with cystic fibrosis. There are very few good quality trials investigating the effect of these medications in cystic fibrosis, and further research is required to investigate the potential role of these medications in improving the outcomes of people with cystic fibrosis.

Steroid/mucokinetic hybrid nanoporous microparticles for pulmonary drug delivery.

In a number of pulmonary diseases, patients may develop abnormally viscous mucus reducing drug efficacy. To increase budesonide diffusion within lung fluid, we developed nanoporous microparticles (NPMPs) composed of budesonide and a mucokinetic, ambroxol hydrochloride, to be inhaled as a dry powder. Budesonide/ambroxol-HCl particles were formulated by spray drying and characterised by various physicochemicals methods. Aerodynamic properties were evaluated using a cascade impactor. Drugs apparent permeability coefficients were calculated across mucus producing Calu-3 cell monolayers cultivated at an air-liquid interface. Microparticles made only from budesonide and ambroxol-HCl had smooth surfaces. In the presence of ammonium carbonate ((NH4)2CO3), NPMPs were formulated, with significantly (P<0.05) superior aerodynamic properties (MMAD=1.87±0.22 µm and FPF=84.0±2.6%). The formation of nanopores and the increase in the specific surface area in the presence of (NH4)2CO3 were mainly attributed to the neutralisation of ambroxol-HCl to form ambroxol base. Thus, ambroxol base could behave in the same manner as budesonide and prompt nanoprecipitation when spray dried from an ethanol/water mix occurs. All formulations were amorphous, which should enhance dissolution rate and diffusion through lung fluid. These NPMPs were able to improve budesonide permeability across mucus producing Calu-3 cell monolayers (P<0.05) suggesting that they should be able to enhance budesonide diffusion in the lungs through viscous mucus.

Recurrent acute rhinosinusitis: a single blind clinical study of N-acetylcysteine vs ambroxol associated to corticosteroid therapy.

The aim of rhinosinusitis treatment is to restore sinusal eutrophism and to normalize ventilation and mucociliary transport. Frequently the improvement of sinusal physiological conditions is associated with a reduction of infections and pulmonary symptoms. The treatment of these diseases often requires the combination of medical and surgical strategies. In particular, the aim of the medical therapy is multiple: to treat the infection (with antibiotics), to reduce the mucosal swelling (with corticosteroids) and to improve mucus drainage (with mucolytics or muco-regulators). The use of atomized nasal douche, as a washing of the nasal fossas, is chosen because of its local action minimizing systemic adverse effects. The surgical treatment is secondary to medical failure, and it is focused on clearing the sinusal ostia in the sphenoethmoidal recess and the osteomeatal complex. In case of recurrent sinonasal diseases the importance of the surgical operation is represented by the fact that the medical treatment better reaches the target in the sinusal space. This study is focused on the primary medical treatment of acute recurrent rhinosinusitis. The patients who immediately needed surgical treatment were excluded from the study (because of the presence of an anatomical obstruction of the osteomeatal complex and/or the sphenoethmoidal recess, hence non-susceptible to improvement by medical therapy alone), and these patients were immediately addressed to undergo a CT scan examination in order to be involved in a future surgical programme. The medical treatment for those forms which do not require antibiotics (i.e. when infections are not involved), is based on the use of topical corticosteroids. While there are controversies on the real efficacy of adding mucolytic agents to the steroids, they are commonly prescribed in clinical practice, with the rationale of reducing viscosity and improving clearance of mucus in order to help the restoration of the physiological sinus conditions. The primary aim of the medical treatment is to reduce the number of acute episodes and thus to increase the time between the exacerbations, allowing a good quality of life without necessitating surgical procedure.

[Impact of treatment with low dose roxithromycin on stable bronchiectasis].

OBJECTIVE: To investigate the impact of treatment with low dose roxithromycin on clinical symptoms and CT scores in patients with stable bronchiectasis. METHODS: Fifty patients with bronchiectasis in stable condition were randomly assigned to a control group and a treatment group. Patients in the control group received ambroxol hydrochloride tablet 90 mg 3 times a day. Patients in the treatment group received roxithromycin disperse tablet 0.15 g every day and ambroxol hydrochloride tablet 90 mg 3 times a day. The course of treatment lasted for 6 months. Quality of life was assessed using St. George's respiratory questionnaire (SGRQ). The British Medical Research Council (MRC) dyspnea scale was used to assess the degree of dyspnea. The score for CT evaluation of the thorax, quality of life and SGRQ were performed for all patients before and after the treatment. RESULTS: After 6 months, the scores for quality of life (48 ± 13) were lower compared to that (58 ± 15) before treatment in the control group; however, the scores for bronchial wall thickening of bronchiectasis (1.8 ± 0.5) were higher than that (1.8 ± 0.4) before study. The scores for the extent of bronchiectasis (2.7 ± 1.6), the bronchial wall thickening of bronchiectasis (1.3 ± 0.4) and the global CT score (6.7 ± 2.5) were reduced after treatment as compared to those before treatment [(4.8 ± 2.3), (1.8 ± 0.5), (9.5 ± 3.3)] in the treatment group, (all P < 0.01). The degree of dyspnea (1.3 ± 0.4) and quality of life (42 ± 12) were lower than those before treatment [(1.89 ± 0.45), (56 ± 15)] in the treatment group. Furthermore, the scores for extent of bronchiectasis (2.7 ± 1.6), the scores for the bronchial wall thickening of bronchiectasis (1.3 ± 0.4) and the global CT score (6.7 ± 2.5) in the treatment group were significantly improved as compared with those [(4.8 ± 2.0), (1.8 ± 0.5), (9.7 ± 3.6)] in the control group respectively after treatment. At the same time, the degree of dyspnea (1.3 ± 0.4) in the treatment group was significantly improved as compared with that (1.7 ± 0.4) in the control group after treatment. CONCLUSIONS: The scores for the bronchial wall thickening of bronchiectasis were increased in patients with stable bronchiectasis. Low dose roxithromycin combined with ambroxol hydrochloride significantly improved degree of dyspnea, reduced scores for extent of bronchiectasis, scores for the bronchial wall thickening of bronchiectasis and the global CT score as compared to treatment with ambroxol hydrochloride alone in patients with bronchiectasis in stable condition.

The differential effect of intrathecal Nav1.8 blockers on the induction and maintenance of capsaicin- and peripheral ischemia-induced mechanical allodynia and thermal hyperalgesia.

BACKGROUND: It has been reported that the selective blockade of Nav1.8 sodium channels could be a possible target for the development of analgesics without unwanted side effects. However, the precise role of spinal Nav1.8 in the induction and maintenance of persistent pain, e.g., mechanical allodynia (MA) and thermal hyperalgesia (TH), is not clear. We designed this study to investigate whether spinal Nav1.8 contributes to capsaicin-induced and peripheral ischemia-induced MA and TH. METHODS: The Nav1.8 blockers, A-803467 or ambroxol, were injected intrathecally either before or after intraplantar capsaicin injection. To evaluate capsaicin-induced neuronal activation in the spinal cord, we quantified the number of Fos-immunoreactive cells in the dorsal horn. In the thrombus-induced ischemic pain model, we determined the differential effect of A-803467 on the induction phase or maintenance phase of MA. RESULTS: Intrathecal injection of A-803467 (10, 30, 100 nmol) or ambroxol (241, 724, 2410 nmol) before intraplantar injection of capsaicin dose dependently prevented the induction of both MA and TH. However, posttreatment with A-803467 (100 nmol) and ambroxol (2410 nmol) did not reduce the MA that had already developed, but did significantly suppress capsaicin-induced TH. Moreover, the capsaicin-induced increase of spinal Fos-immunoreactive cells was significantly diminished by pretreatment, but not posttreatment with Nav1.8 blockers. In thrombus-induced ischemic pain rats, repetitive treatments of A-803467 during the induction period also prevented the development of MA, whereas A-803467 treatments during the maintenance period were ineffective in preventing or reducing MA. CONCLUSIONS: These results demonstrate that spinal activation of Nav1.8 mediates the early induction of MA, but not the maintenance of MA. However, both the induction and maintenance of TH are modulated by the intrathecal injection of Nav1.8 blockers. These findings suggest that early treatment with a Nav1.8 blocker can be an important factor in the clinical management of chronic MA associated with inflammatory and ischemic pain.

High-dose ambroxol reduces pulmonary complications in patients with acute cervical spinal cord injury after surgery.

BACKGROUND: Ambroxol has a very high affinity for lung tissues; its concentration is approximately 20 times higher in the lung than in the serum. We aimed to evaluate the effectiveness of high-dose ambroxol (990 mg/day) in the improvement of oxygenation and prevention of postoperative respiratory complications in the patients with acute cervical spinal cord injury (CSCI). METHODS: A total of 61 acute CSCI patients admitted to the Intensive Care Unit (ICU) of our hospital between January 2009 and June 2011 were included in the study. They were graded as ASIA A and ASIA B according to the classification of the American Spinal Injury Association (ASIA) and were randomly divided into two groups: one group received intravenous ambroxol at 990 mg/day for 5 consecutive days after operation; the other group treated without ambroxol served as control. The results of arterial blood gas analysis on postoperative day 3 and 5 and occurrence of pulmonary complications within 5 days after operation were evaluated. RESULTS: The group treated with high-dose ambroxol showed a lower rate of postoperative pneumonia and hypoxemia within 5 days after operation. On the 3rd and 5th days, the oxygenation index in the high-dose ambroxol group (291.02 ± 34.96 and 301.28 ± 37.69) was significantly higher than in the control group (230.08 ± 26.25 and 253.82 ± 26.26), with significant differences between the two groups (P = 0.045 and 0.041). CONCLUSION: Administration of high-dose ambroxol should be considered as an alternative and effective approach to reduce the postoperative respiratory complications and improve the oxygenation status in acute CSCI patients.

Fast-track pulmonary conditioning before urgent cardiac surgery in patients with insufficiently treated chronic obstructive pulmonary disease.

AIM: Chronic obstructive pulmonary disease (COPD) is an important risk factor for perioperative morbidity and mortality in patients undergoing cardiac surgery. Despite high clinical relevance, current guidelines lack clear recommendations on the optimal approach for patients with insufficiently treated COPD and urgent need for cardiac surgery. The aim of the present study was to analyze the efficacy of short-term pulmonary conditioning (PC) in this subset of cardiopulmonary patients. METHODS: Eighteen patients with urgent need for cardiac surgery were treated with 1 mg budenoside twice a day, 1.25 mg salbutamol four times a day and 15 mg ambroxol three times a day. On average, patients received pulmonary conditioning for 5.1 ± 2.1 days. Lung function was assessed before and after treatment. RESULTS: Pulmonary conditioning improved forced expiratory volume in one second (FEV1) by 16% (P<0.001). Predicted FEV1 increased from 48.3 ± 13.6% at baseline to 55.4 ± 16.1% after treatment (P<0.001). Total resistance was reduced from 0.933 ± 0.418 kPa·s/L to 0.631 ± 0.344 kPa·s/L after PC (P=0.004). The percentage of patients in GOLD stages III-IV was reduced from 55.6% at baseline to 27.8% after treatment. After surgery, patients needed mechanical ventilation for 2 ± 3.4 days. One patient (5.6%) received a tracheostomy and four patients (22.2%) developed pneumonia; 30-day mortality was 5.6%. CONCLUSION: Short-term treatment with budenoside, salbutamol and ambroxol significantly improved lung function parameters. If surgery can be delayed for several days, pulmonary conditioning should be considered for patients with insufficiently treated COPD.

[Antenatal ambroxol administration for prevention of respiratopry distress syndrome in preterm infants: preliminary report].

UNLABELLED: The rate of preterm births has remained unchanged for the recent years despite of the persistent attempts to diminish it. Preterm births are responsible for about 70% of neonatal morbidity and mortality. One of the main problems of preterm newborns is their lung immaturity. The aim of this study is to assess the effect of Ambroxol, given prenatally on the rate and severity of neonatal respiratory distress syndrome (NRDS) in preterm infants and its potential to replace the corticosteroid prophylaxis in cases where steroids are contraindicated or undesirable. MATERIALS AND METHODS: The trial consisted of 33 pregnant women between 27 and 32 week of gestation. 17 of them represented our work group and were given Ambroxol syrup 15 mg/ml, per os 30 ml in three intakes, for 7 days. 16 were controls and were not given any kind of NRDS prophylaxis. RESULTS: severe NRDS was diagnosed in 2.5 times more cases in the control group compared to the work group. All infants in the control group had clinical signs of NRDS, while 23.5% of the infants in the work group were asymptomatic. Bronchopulmonary dysplasia was diagnosed in 25% of the infants in the control group, compared to none diagnosed in the work group. Newborns with no antenatal NRDS prophylaxis had to be kept in intensive care units for an average period of time twice longer than the newborns to mothers who had received Ambroxol. CONCLUSIONS: Antenatal Ambroxol administration diminishes the rate of NRDS, decreases the duration, scope and price of the intensive care, lessens the duration of assisted ventilation and oxygen needs and hence improves the long-term outcome. Ambroxol and steroids have cumulative effect on fetal lung maturation and therefore should both be a part of the preterm delivery therapeutic scheme.