The perfused rat lung as a model for studies on the formation of surfactant and the effect of Ambroxol on this process

Post, Martin; Batenburg, Joseph J.; Schuurmans, E. A. J. M.; Oldenborg, V.; Molen, Aart J. van der; Golde, L.M.G. Van

doi:10.1007/bf02713884

Cited by 38 publications

(22 citation statements)

References 32 publications

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“…Ambroxol has been shown to stimulate surfactant secretion [116,117]. However, LUSUARDI et al [92] report only an insignificant increase of BAL phospholipids in COPD patients treated with 150 mg ambroxol·day -1 for 2 weeks.…”

Section: Conventional Antiobstructive Therapymentioning

confidence: 99%

The role of pulmonary surfactant in obstructive airways disease

Hohlfeld

Fabel²,

Hamm³

1997

Eur Respir J

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Pulmonary surfactant research has an increasing impact on treatment considerations in adult respiratory disorders, above all acute respiratory distress syndrome (ARDS). Obstructive airways diseases have only been sporadically addressed in this respect. In the last decade, direct and circumstantial evidence for surfactant as a contributing factor in the regulation of airway calibre has emerged.Morphologically, a bronchiolar surfactant layer has been demonstrated, whereby the airways are mostly supplied by alveolar surfactant components via the mucociliary escalator. Functionally, prevention of airway film collapse and collapse of the airway walls are important surfactant properties in maintaining airway stability. In addition to its surface activity, airway surfactant improves bronchial clearance and regulates airway liquid balance, thus indirectly modulating airway wall thickness and airway diameter. Surfactant has furthermore been shown to modulate the function of respiratory inflammatory cells. Its immunomodulatory activity includes suppression of cytokine secretion and transcription factor activation. This may be of importance in the inflammatory network of asthma.Thus, dysfunction of surfactant in obstructive lung disease might be one of the mechanisms leading to increased airway resistance, which is commonly thought to be due to narrowing of airways under humoral and nervous control. In animal models of asthma, surfactant dysfunction was demonstrated, which was possibly due to protein inhibition. Furthermore, surfactant therapy seems to be capable of preventing allergen-induced bronchoconstriction. Human studies on surfactant impairment in obstructive airways diseases are still scarce but the data available are consistent with animal studies.Antiobstructive pharmacotherapy, mainly with corticosteroids, might influence and improve airway surfactant balance, but the exact mechanisms and the overall effect of pharmacotherapy on surfactant function in obstructive airways disease has to be further elucidated. Our knowledge about the role of pulmonary surfactant in obstructive airways disease is still limited, but there is convincing evidence that pulmonary surfactant plays a role in keeping the airways open.

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Section: Conventional Antiobstructive Therapymentioning

confidence: 99%

The role of pulmonary surfactant in obstructive airways disease

Hohlfeld

Fabel²,

Hamm³

1997

Eur Respir J

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“…Animal studies showed that it enhances both bronchial glandular cell secretions [1 ] and the production of alveolar type II pneumocyte surfactant [2][3][4][5][6][7][8]. It also stimu lates ciliary motility [9,10] and accelerates mucociliary transport [11,12].…”

Section: Introductionmentioning

confidence: 99%

Clinical Efficacy of Ambroxol in the Treatment of Bronchial Stasis. Clinical Trial in 120 Patients at Two Different Doses

Germouty

Jirou-Najou²

1987

Respiration

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Mucosolvan is a ‘mucus-modifier’ whose active compound is ambroxol. The aim of our research was to determine its clinical efficacy in the treatment of bronchial stasis by carrying out two successive double-blind studies in two parallel groups of patients and comparing ambroxol with placebo in a treatment lasting 10 days. The first trial involving 60 patients daily treated with 120 mg of ambroxol showed significant differences (p < 0.05) in sputum volume, sputum viscosity, difficulty of expectoration, and severity of cough when compared with the placebo group. The two groups of patients were initially well matched and the drug was well tolerated. In a second trial involving 60 new patients daily treated with 30 mg of ambroxol, the drug showed no clear clinical effects. We conclude that ambroxol is an effective ‘mucus modifier’ and is well tolerated at a dose of 120 mg/day.

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“…The fact that acebrophylline induced the uptake not only of labeled choline but also of 32 Pphosphate suggests it acts on two levels on surfactant synthesis: the first involves ambroxol's estab- lished action on phosphocholine-cytidyl-transferase [25,26] and the second probably because of theophylline-7 acetic acid's action on choline-kinase [22] (fig. 3).…”

Section: ) Synthesis and Release Of Pulmonary Surfactantmentioning

confidence: 99%

Acebrophylline: an airway mucoregulator and anti-inflammatory agent

Pozzi

2016

Monaldi Arch Chest Dis

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Acebrophylline is an airway mucus regulator with antiinflammatory action. The drug’s approach involves several points of attack in obstructive airway disease. The molecule contains ambroxol, which facilitates various steps in the biosynthesis of pulmonary surfactant, theophylline-7 acetic acid whose carrier function raises blood levels of ambroxol, thus rapidly and intensely stimulating surfactant production. The resulting reduction in the viscosity and adhesivity of the mucus greatly improves ciliary clearance. By deviating phosphatidylcholine towards surfactant synthesis, making it no longer available for the synthesis of inflammatory mediators such as the leukotrienes, acebrophylline also exerts an inflammatory effect. This is confirmed in vivo by the reduction in aspecific bronchial hyperresponsiveness in patients with stable bronchial asthma. On a clinical level, acebrophylline is therapeutically effective in patients with acute or chronic bronchitis, chronic obstructive or asthma-like bronchitis and recurrence of chronic bronchitis; it reduces the frequency of episodes of bronchial obstruction and reduces the need for β2-agonists, and improves indexes of ventilatory function.

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The perfused rat lung as a model for studies on the formation of surfactant and the effect of Ambroxol on this process

Cited by 38 publications

References 32 publications

The role of pulmonary surfactant in obstructive airways disease

The role of pulmonary surfactant in obstructive airways disease

Clinical Efficacy of Ambroxol in the Treatment of Bronchial Stasis. Clinical Trial in 120 Patients at Two Different Doses

Acebrophylline: an airway mucoregulator and anti-inflammatory agent

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