A controlled trial of ambroxol in chronic bronchitis.

Ambroxol is a mucolytic agent which is widely used in chronic bronchitis in Europe. We conducted a double-blind randomized controlled trial of ambroxol vs matched placebo in 90 patients with chronic bronchitis and difficulty clearing secretions. It was concluded that there was no advantage to taking ambroxol.

Effects of a beta adrenergic drug and a secretolytic agent on regional mucociliary clearance in patients with COLD.

The effect of clenbuterol, a beta adrenergic drug, and ambroxol, a secretolytic agent, on regional mucociliary clearance and pulmonary radioaerosol distribution was investigated in two groups of 15 patients with COLD in a double-blind cross-over trial with placebo. Clearance rates of inhaled 99mTc-labelled human serum albumin minimicrospheres (HAMM) were determined over upper, middle, lower, central, and peripheral anterior lung regions. Additionally, an index was employed for quantitative analysis of initial pulmonary aerosol distribution in order to detect changes in the site of particle deposition caused by the drugs. Regional measurement of tracheobronchial particle clearance showed clenbuterol to have a significant (P less than 0.05) stimulating effect in 4 of 5 tested pulmonary zones resulting in significantly accelerated whole lung clearance. Ambroxol was effective in only 1 of 5 tested lung areas and did not prove to enhance whole lung clearance significantly. The secretolytic agent was associated with significant (P less than 0.05) improvement of lung aerosol distribution in obstructive emphysematous patients, whereas no significant change in lung deposition of the inhaled particles was encountered in the patients with chronic obstructive bronchitis after either drug regimen.

Therapeutic activity of ambroxol theophyllinacetate in chronic obstructive pulmonary diseases.

In an open study, 50 patients suffering from chronic obstructive pulmonary disease in an acute infectious phase were treated with ambroxol theophyllinacetate. The drug was given orally in a dosage of 100 mg BID for ten days. Viscosimetric data showed a significant decrease of viscosity of the mucus, leading to easier expectoration and reduction in the severity and frequency of cough. These improvements had positive effects on respiratory function and on the condition of the patients.

Increased incorporation of fatty acids into phospholipids of lungs and livers of rabbits under the influence of bromhexine and ambroxol.

The incorporation of lauric acid, palmitic acid and oleic acid into phospholipids of lung and liver has been studied in tissue slices of control rabbits and of rabbits treated with bromhexine or ambroxol in doses of 10 mg/kg. A marked increase (up to 200% of the controls) of palmitic acid incorporation into phosphatidylcholine (lecithin) and phosphatidylethanolamine of the lung was found whereas the incorporation rate of palmitic acid into lecithin and phosphatidylethanolamine of the liver displayed no significant change. The incorporation of lauric acid and oleic acid into lung phospholipids was not accelerated. The observed effects were more marked in short time experiments (analysis 2 h after drug injection) than after treatements for 7 days. It is concluded that the phospholipid synthesis is stimulated by the drugs especially in the lungs. This seems to be of particular interest with respect to the surfactant system of the lung and might have some therapeutic relevance.

The effects of Oradexone and Ambroxol pretreatment of the oxidative sensitivity of the red blood cells in preterm infants.

The antioxidant enzyme activities and lipid peroxidation in the red blood cells of cord blood were investigated and compared at different gestation times in preterm and full-term neonates, with and without pretreatment of the pregnant mothers with Oradexone (Dexamethasone) or Ambroxol. Administration of the two drugs not only stimulated the lung surfactant system, but also exerted favourable effects on the antioxidant enzyme activities while the lipid peroxidation was decreased.

Surfactant in the amniotic fluid and bromhexine metabolite VIII.

The effect of metabolite VIII of bromhexine on surfactant content in the amniotic fluid was investigated in a double blind study. Administration of 100 and 200 mg NA-872 daily for 5 days to pregnant women ranging in gestational age from 196 to 243 days was not followed by a significant rise in the L/S ratio.

Possibility of interaction among antibiotics and mucolytics in children.

A controlled clinical trial in children with acute infections of the lower respiratory tract was carried out to see whether or not treatment with ambroxol could bring about faster and better results. One hundred twenty children with acute lower respiratory tract infections were all given antibiotics plus, at random, either ambroxol (1.5-2.0 mg/kg body weight orally) or a placebo. The duration of the trial was ten days. All the patients in both groups were cured clinically. However, remission of the cough, of the chest pathological signs, as well as the improvement of the lung radiographical pictures were significantly more rapid in children treated with ambroxol than in those who received the antibiotic alone. Ambroxol was tolerated perfectly by all the children.

Ambroxol and pulmonary toxicity induced by antineoplastic drugs.

The authors describe the potential effects of ambroxol on the pulmonary disorders induced by antineoplastic agents (in particular, bleomycin and the nitrosureas). An experimental stage focussed attention on the early modifications occurring in the alveolar surfactant and in the afflux of inflammatory and immune-effector cells following bleomycin-induced lung fibrosis in the rat (by intratracheal instillation). The ambroxol-protected rats showed a slower drop of alveolar lecithins in the first few hours after bleomycin administration and a lower afflux of neutrophils, macrophages and lymphocytes. In the clinical stage, respiratory function was studied in two groups of cancer patients treated with nitrosureas or bleomycin. Preliminary findings indicate a rapid worsening of some functional parameters--maximal expiratory flow at 25% vital capacity, diffusing capacity for carbon monoxide and diffusing capacity/ventilation--in controls, while no such changes occurred in the ambroxol-protected subjects. The possible pathogenetic implications of these results and perspective for future investigations are discussed.

Ambroxol for prophylaxis and treatment of bronchopulmonary complications after chest surgery.

A double-blind clinical trial has been carried out with 40 patients hospitalized for thoracic pathology requiring surgery (cancer of the lungs, hamartoma, pleural mesothelioma, bullous dystrophy or emphysema of the lung). The purpose was to determine the effectiveness of the drug in preventing and in treating postoperative bronchopulmonary complications. The results showed that the patients treated with 1g of ambroxol for three days before surgery, on the day of the operation and for five days afterwards had a more rapid turnover of intra-alveolar surface tension and better re-expansion of the pulmonary parenchyma after surgery. They also had better mucociliary clearance of the respiratory tract. These improvements are indispensable for limiting bronchopulmonary complications after chest surgery.

Lack of effect of ambroxol, a bronchial secretolytic agent, on gastric mucus in man.

The effect of ambroxol, a bronchial mucolytic agent, on gastric mucus was investigated in man. Ten patients with bronchial hypersecretion were treated with ambroxol 30 mg t.i.d. by the oral route for 10 days. Before and after treatment the amount of total mucoproteins in the gastric juice was measured and a 'mucoprotective index' was calculated. Neither quantitative nor qualitative changes in gastric mucus were observed after ambroxol treatment. Our results show that the drug does not exert lytic effects on the gastric mucus layer and hence is devoid of damaging activity on the gastric mucosa.

[Ambroxol versus betamethasone for the promotion of antepartum lung maturity in pathological pregnancies]. / Ambroxol versus Betamethason zur Förderung der antepartalen Lungenreife bei pathologischen Schwangerschaften.

Although glucocorticoids have been universally implemented to stimulate fetal lung maturity, their effectiveness and side effects are still widely contested. In search of alternative drugs a double-blind study was conducted between June 1981 and June 1984 comparing betamethasone, a conventional corticoid, and ambroxol, a bromhexine metabolite for efficacy and tolerance in prenatal prevention of the respiratory distress syndrome (RDS) in premature infants and full-term neonates. The therapeutic efficacies of betamethasone and ambroxol for this indication proved to be comparable. Since the possible risks of corticoid therapy in abnormal pregnancies are repeatedly discussed in the literature and in daily clinical practice. 137 patients with EPH gestosis, placental insufficiency, diabetes mellitus, and premature rupture of the membranes were selected from the original group of 308 patients. Only minor side effects (e.g. nausea) were present in a few of the 137 cases undergoing treatment with the 2 test substances. No side effects were observed in the neonates. The incidence of fetal RDS was comparable in both groups (2.9% with ambroxol, 2.2% with betamethasone). Transient and mild RDS cases were slightly more frequent in the ambroxol group than in the betamethasone group. To date, contraindications to ambroxol treatment in abnormal pregnancies are unknown and since generally the rate of potential side effects is considered to be lower in comparison with corticoid treatment, the use of ambroxol especially in abnormal pregnancies corresponding indication can be recommended.

A study of cellular immunity in newborns after prevention of respiratory distress syndrome (RDS).

Cellular immune responsiveness against infections was evaluated in four groups of newborns. The first group was composed of preterm newborns whose mothers had received betamethasone for prevention of RDS, the second group of preterm newborns whose mothers had received ambroxol for prevention of RDS, the third group of preterm newborns whose mothers had not received any drug enhancing surfactant production, and the fourth group were healthy-term infants. A reduction of OKT4+ cells and functional deficits of neutrophils were found in preterm infants born to mothers treated with steroids, whereas no functional abnormalities of immune-competent cells were observed in preterm infants born to mothers treated with ambroxol.

Normalization of bronchial exocrine pathology after endobronchial treatment with ambroxol.

A clinical study was performed on nine adult in-patients suffering from chronic intercrisis bronchopneumopathy, to evaluate whether a local endobronchial treatment with ambroxol could be effective in stabilizing the secretory activity of bronchial glands modified by phlogistic injury. The patients underwent bronchoscopic examination and deep biopsy, before and after treatment with local medication of ambroxol every other day for 30 days. In addition to morphometric measurements, detailed histochemical examinations were performed on the secretion of mucous acinic and glandular excretory ducts. The trial proved that the treatment with ambroxol stimulates serous acini, restoring normal production of sulphomucins and also of mucous acini, increasing the metabolic activities of acid glycoproteins and proportionally curtailing the excessive synthesis of glycoproteins. Ambroxol can therefore be considered a mucoregulating drug.

[The effect of ambroxol and bromhexine on the "respiratory burst" of alveolar macrophages]. / Einfluss von Ambroxol und Bromhexin auf den "Respiratory Burst" von Alveolarmakrophagen.

The effect of ambroxol and bromhexine on the yeast cell wall- and arachidonic acid (AA)-induced luminol-respectively lucigenin-dependent chemiluminescence (CL) of alveolar macrophages (AM) of patients with lung diseases has been investigated. Both drugs cause a suppression of the induced CL. These results suggest that ambroxol and bromhexine reduce the generation of reactive oxygen metabolites (ROM) by AM. The mechanism of action is thought to involve the activation of the acyl-CoA: lysophosphatide acyltransferase. The increase of this enzyme activity lowers probably the intracellular concentration of free AA and consequently also the production of ROM. The investigations show a new possibility for the influence of biosynthesis of ROM and likely of eicosanoids, which play an important role as pathogenetic mediators in different lung diseases.

[Combination of oral bacterial vaccines and antibiotics in acute recurrent respiratory infections]. / Sull'associazione vaccino batterico orale e antibiotici in corso di infezioni respiratorie acute ricorrenti.

The authors treated 34 patients with acute bronchopulmonary disease or flare-ups of chronic ones with equal doses of ambroxol and ceftriaxone considering the homogeneity of the morbid processes. Patients were divided into two groups of 17 subjects each: group A was given a polyvalent oral bacterial vaccine, group B a placebo. Relevant differences were found between the experimental and control groups concerning cough (score: A = 108, B = 119), duration of expectoration (A = 5.3 days, B = 6.4 days), duration of antibiotic therapy (A = 8.0 days, B = 8.8 days), and length of hospitalization (A = 10.9 days, B = 12.0 days). Differences were slight as far as duration of fever, characteristics of cough and objective findings on the chest were concerned.

Clinical trial of ambroxol (Mucosolvan) in Sjögren's syndrome.

A clinical trial is described in which twelve patients with Sjögren's Syndrome (SS) were given a dose of 135 mg ambroxol (Mucosolvan) daily for eight weeks. Nine of the patients completed the trial. Three patients dropped out because they developed side effects (generalized rashes in two patients and stomatitis in one). The side effects, however, were mild and cleared off after cessation of treatment. Ambroxol improved sicca symptoms, especially ocular symptoms, in the SS patients, although lacrimal and salivary gland functions measured by Schirmer test or gum test were not changed. Furthermore, the treatment did not alter any chemical findings determined in the stimulated tear and saliva. Our results suggest that ambroxol is useful for the management of sicca symptoms in some patients with SS.

[Study of the activity of ambroxol in children with aspecific bronchial hyperreactivity]. / Studio sull'attività dell'Ambroxol in bambini con iperreattività bronchiale aspecifica.

The authors examined the action of non-specific bronchial reactivity to methacholine (IBA) before and after treatment with ambroxol in a group of a children with clinic symptomatology of recurrent cough and/or rhinitis. The little patients are selected from a pediatric population that, besides the clinical data mentioned above, had a high probability to manifest nonspecific bronchial reactivity for which clinical and anamnestic data predisposed. In all patients were carried out an allergologic examination with the execution of Prick test and determination of total IgE. The results obtained and discussed suggest a favorable employ of the drug that is able to normalize the functional condition of the bronchial mucous membrane and of the ciliary apparatus which alteration are frequently present in subjects with high non-specific bronchial reactivity.

[Prophylaxis and treatment of bronchopulmonary complications with ambroxol administered by infusion in elderly patients undergoing surgery]. / Prevenzione e trattamento delle complicanze broncopolmonari con ambroxol per infusione negli operandi anziani.

The Authors consider the high number of patients who are affected with chronic obstructive bronchitis due to various factors (cigarettes smoking, infections, pollution, reduced immune response). These patients, when submitted to middle-high abdominal surgery in total anaesthesia of middle-long duration, are at increased risk due to pulmonary complications. Therefore, an adequate respiratory protection is necessary; actually it is possible with high dose of Ambroxol (1 g). Two groups, both of 35 patients, were compared; the first group was treated with Ambroxol 1 g the second one with aminophilline, bromexine, B2 adrenergic agonists, corticosteroids. The results show the efficacy of respiratory protection by using Ambroxol 1g.