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Lacrimal and salivary secretion in Sjögren's syndrome: the effect of systemic treatment with bromhexine.

In a randomized clinical study, 32 patients with Sjögrens syndrome (SS) were given placebo/bromhexine (Bisolvon) 48 mg daily for 3 weeks. Various ophthalmological and oral variables as well as different proteins in tear fluid and saliva were registered. Bromhexine stimulated the tear secretion significantly, presumably without changing the protein composition of the tear fluid. In saliva the IgM concentration in contrast to other proteins decreased in patients with high pre-treatment values. Bromhexine may be of valuable help in the treatment of some patients with SS.

Aged↗

Italian multicenter study on the treatment of chronic obstructive lung disease with bromhexine. A double-blind placebo-controlled trial.

237 out-patients suffering from chronic obstructive lung disease (COLD) were selected from 7 Italian clinical centers. They were randomly allocated to either placebo or bromhexine 30 mg b.i.d. p.o., in a double-blind fashion. Sputum volume and quality, facility of expectoration, cough, dyspnea, auscultatory thoracic symptoms, forced expiratory volume, peak expiratory flow rate and residual volume were evaluated. Bromhexine showed a statistically significant therapeutic activity in comparison to placebo. This action was rapid, marked and effective in determining a modulation of bronchial secretions.

Adult↗

Mediastinal pancreatic pseudocyst caused by obstruction of the pancreatic duct was eliminated by bromhexine hydrochloride.

A 49-year-old man, who had a 30-year history of drinking the equivalent of 80 g of ethanol per day, underwent a detailed medical examination for cough and dyspnea. Chest-abdominal computed tomography and endoscopic retrograde pancreatography led to the diagnosis of a mediastinal pancreatic pseudocyst resulting from obstruction of the pancreatic duct by a protein plug. The pseudocyst rapidly improved with conservative treatment with camostat mesilate, H2-receptor antagonist and digestive enzymes. Although the patient abstained from alcohol for approximately 6 months, he resumed drinking, leading to recurrent attacks of pancreatitis. Bromhexine hydrochloride was then administered for 6 months, with the expectation that it would have a mucolytic effect on the pancreatic juice, resulting in improvement in the clinical symptoms, pancreatic enzymes and pancreatic exocrine function, as well as elimination of the protein plug. Bromhexine hydrochloride may be a new therapy for pathological states, such as alcoholic chronic pancreatitis, in which there is increased viscosity of the pancreatic juice because of elevated protein concentration, leading to protein plug formation and temporary blockage of the pancreatic duct.

Bromhexine↗

Bromhexine treatment of Sjögren's syndrome: effect on lacrimal and salivary secretion, and on proteins in tear fluid and saliva.

In a randomized clinical study, 32 patients with Sögren's syndrome (SS were given placebo/bromhexine (Bisolvon) 48 mg daily for 3 weeks. Various ophthalmological and oral variables as well as different proteins in the tear fluid and saliva were registered. Bromhexine stimulated the tear secretion significantly, presumable without changing the protein composition of the tear fluid. In contrast to other proteins in saliva the IgM concentration decreased in patients with high pre-treatment values. Bromhexine may be of valuable help in the treatment of some patients with SS.

Adult↗

[Experimental investigations on the influence of bromhexine hydrochloride on the excretion of lacrimal fluid].

The influence of bromhexine hydrochloride on the excretion of the lacrimal fluid in rabbits was investigated by means of lysozyme test. The investigations showed that the application of the compound is leading to a considerable increase of excretion of tears. It reaches its maximum after ca. 2 hours from the moment of application when the production of tears is ca. 80 p.c. larger than before it. This suggests the possibility of application of bromhexine hydrochloride in the therapy of keratoconjunctivitis sicca.

Animals↗

[The existence of sinusitis in rabbits and the use of bromhexine as a mucolytic nose drop in the treatment of sinusitis].

To make an experimental sinusitis, 38 maxillary sinus ostia of 19 rabbits were closed by silicon plastic and 24 hours later 10(8)-10(10) germs/ml. of Streptococcus pneumoniae type C III were given to the antrums of sinuses. 5 days later all the rabbits showed sinusitis clinically, radiologically, bacteriologically and histopathologically. Viscous, purulent secretions collected in the antrums of sinuses. We thought that the medical treatment of sinuses which had drainage treatment necessitated to decrease the viscosity of secretions. Because of this bromhexine as a mucolytic nose drop was investigated for the first time for the treatment of sinusitis in two groups of rabbits. As a result of the study bromhexine as a nose drop in the eradication of sinus infections was seen a useful drug.

Administration, Intranasal↗

Effect of bromhexine on nasal mucus clearance in chronic maxillary sinusitis.

Nasal mucus clearance (NMC) was studied in seventy patients with chronic maxillary sinusitis. Forty-five patients were treated with oral administration of bromhexine tablets along with oral antibiotics and nasal decongestants. Twenty-five patients received the same treatment but without bromhexine to evaluate the results. NMC was also studied in hundred healthy controls.

Bromhexine↗

[The effect of ambroxol and bromhexine on the "respiratory burst" of alveolar macrophages].

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.

Acridines↗

The effect of bromhexine on the kidney lesions in NZB-NZW-F1 mice.

The NZB-NZW-F1 mice develop a clinical picture resembling SLE and an exocrinopathy resembling Sjögren's syndrome. Three groups of hybrids were treated from their 20th week of age for 10, 17 and 20 weeks (groups 1, 2, 3) with Bromhexine in two different concentrations--6 & 60 mg/kg and placebo. NMRJ mice treated with placebo acted as healthy controls. After the treatment the kidneys were examined by light microscopy. The kidneys exhibited lupus-like lesions. Animals treated with 60 mg/kg Bromhexine for 17 weeks had a significantly lower degree of changes than had the other hybrids.

Animals↗

Bromhexine in severe asthma.

Fourteen patients with acute severe asthma necessitating hospital admission were all treated with a standard therapeutic regimen, and in addition received either bromhexine or placebo (initially intravenously and subsequently orally) double-blind. We were unable to show any significant improvement in the rate of recovery of the bromhexine-treated group, in terms of either arterial blood gases or change in peak expiratory flow rates.

Acute Disease↗

[Clinical results in the treatment of chronic obstructive bronchitis with ambroxol in comparison with bromhexine (author's transl)].

Preclinical studies of trans-4-[(2-amino-3,5-dibromobenzyl)-amino]-cyclohexanol hydrochloride (ambroxol, NA 872), the metabolite VIII of bromhexine, show that it is superior to the basic substance with respect to its bronchosecretolytic properties. In a double blind study 30 patients suffering from chronic obstructive bronchitis received in randomized order 36 mg bromhexine/d or 45 mg ambroxol/d, each over a period of 4 weeks. The following parameters were studied: mean bronchial flow resistance, forced expiratory volume, static lung volumes, arterial blood gases as well as clinical and laboratory results. Bromhexine was not associated with a change in lung function parameters. Ambroxol was associated with a 25% reduction of the average bronchial flow resistance. The forced expiratory volume improved over the period on the average by 14%. Patients with slight arterial hypoxemia had an increase in the partial pressure of arterial oxygen. The patients found both substances facilitated expectoration. Further studies appear necessary to confirm the improved respiratory performance under the influence of ambroxol.

Adult↗

Bromhexine for otitis media with effusion.

As one of the causes of persistence of otitis media with effusion is reputed to be the viscidity of the mucoid effusion in the middle ear, a double-blind drug trial with a mucolytic agent, bromhexine hydrochloride, was carried out. There were 97 affected ears in the active group and 98 ears in the placebo group. There was 3.6 times the resolution rate in the active group and the results were not related to the size of the adenoids nor the season. This study shows that bromhexine hydrochloride is a valuable adjunct in the treatment of otitis media with effusion.

Adenoids↗

Enhancement of spiramycin concentration by bromhexin in the bovine nasal secretions.

Intramuscular injection of bromhexin (Quentan) results in increased bioavailability of spiramycin in nasal secretions. In the presence of a mucolytic agent, the area under the curve calculated according to spiramycin concentrations found in nasal secretions increases by 6%, 41% and 32% respectively in the course of three days of treatment. This potentiation reveals the interest involved in administering a combination of bromhexine and antibiotics in the treatment of infectious diseases of the respiratory tract.

Animals↗

Clinical effectiveness of a combination of bromhexine and amoxicillin in lower respiratory tract infection. A randomized controlled trial.

A multicenter double-blind randomized trial was performed in 22 teaching hospitals to compare the clinical effectiveness of the combination of amoxicillin (CAS 26787-78-0) plus bromhexine (CAS 3572-43-8) versus amoxicillin alone given 4 times a day for 5 to 7 days in the treatment of clinically diagnosed community-acquired bacterial lower respiratory tract infections. 392 adult patients diagnosed clinically to have acute bronchitis or pneumonia of bacterial etiology were recruited for the study with 192 subjects given amoxicillin (250 mg) plus bromhexine (8 mg) (Drug AB) and 200 receiving amoxicillin (250 mg) (Drug AA) alone 4 times a day for 5 to 7 days. Clinical response, improvement in symptom scores using a visual analogue scale, and bacteriologic response were monitored at Days 3, 5 and 7 of treatment. Results showed that although 180/192 (94%) given Drug AB and 185/200 (93%) given Drug AA had favorable clinical response at the end of treatment, the infection was completely resolved for 89/192 (46%) among the Drug AB group and in 67/200 (34%) of patients on Drug AA (p = 0.022). Also, patients given Drug AB had significantly greater reduction of their symptom scores at Day 3 for symptoms of cough discomfort, cough frequency, ease of expectoration and sputum volume. Among the subset of patients with pneumonia, the cure rates for Drug AB and Drug AA were 24/50 (47%) and 11/50 (22%), respectively (p = 0.008). A respiratory pathogen was cultured in only 72/392 (18%) of subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Experimental studies on the question of an adjuvant function of bromhexine].

On a possible adjuvant function of a bronchosecretolytic preparation commercially available, N-cyclohexyl-N-methyl-(2-amino-3,5-dibromobenzyl)-amine-hydrochloride (bromhexine, Bisolvon-R), sensibilization tests on 30 rabbits were undertaken. 5 animals received Bisolvon and human albumin as antigen, 5 rabbits human albumin only, 5 rabbits Bisolvon and human lymphocytes, 5 rabbits human lymphocytes only, 5 rabbits Bisolvon alone, and 5 received neither Bisolvon nor any antigen. The techniques in these studies, such as two-dimensional double immunodiffusion in agar gel, lymphocytotoxicity test, mixed lymphocyte culture test, electrophoresis on cellulose-acetate foil were used as well as histologic preparations. It could be ascertained that sensitizing with human albumin and simultaneous application of Bisolvon led to a higher concentration of antibodies against albumin than did sensitizing with human albumin alone. Rabbits sensitized with human lymphocytes showed no obvious difference in their antibody rates whether they had received Bisolvon or not. This applied to cell mediated antibodies as well as to the rate of cytotoxic antibodies against human lymphocytes. Among the histologic findings of spleen, bone marrow showed the morphologic equivalences expected from xenosensitization. Comparing the results of sensitized rabbits with and without Bisolvon there were no positive differences as to intensity and/or type of reactivity to be seen. Liver and kidney showed no considerable pathologic phenomena with the exception of some cases with coccidiosis in the bile ductuli. Concerning the bronchial mucosa, in all rabbits treated with Bisolvon an increase of mucine enriched goblet cells as well as a hypergranulation of different epithelial cell types could be observed. Moreover in all animals, including the controls, an intense lymphatic infilitration in the subepithelial and submucous area was identified. The increased antibody concentration in the sera of animals from group I compared with that of rabbits from group II is interpreted as an enhancement of cell membrane's permeability effected by bromhexine. By this mechanism, on one hand antigen molecules could be absorbed better, while on the other elimination of molecular antibodies, that means immunoglobulins, from plasma cells could be favoured.

Adjuvants, Immunologic↗

Expectorant action of bromhexine in chronic obstructive bronchitis.

Bromhexine was compared with a placebo in a double-blind clinical trial in bronchitic inpatients with mucoid sputum. Oral bromhexine 16 mg. thrice daily for 11 days compared with placebo resulted in a significant increase in sputum volume and significant decrease in sputum viscosity, and changed markedly the rheological characteristics of the sputum. There was, however, no improvement in ventilatory capacity or in the overall respiratory state as assessed by the patients themselves or their clinician. No patient having the drug had side-effects and there was no change in laboratory findings attributable to it.

Adult↗