The lack of effect of benzalkonium chloride on the cilia of the nasal mucosa in patients with perennial allergic rhinitis: a combined functional, light, scanning and transmission electron microscopy study

Braat, J. P. M.; Ainge, G.; Bowles, J. A. K.; Richards, D. H.; Riessen, D. Van; Visser, W.J.; Rijntjes, E.

doi:10.1111/j.1365-2222.1995.tb00398.x

Cited by 50 publications

(39 citation statements)

References 14 publications

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“…Some investigators have concluded that the inclusion of preservatives, such as BAC, in nasal solutions does not cause any adverse biological effects in vivo [20, 21]. However, these data are inconsistent with the numerous in vitro studies characterizing the adverse effects of preservatives on nasal mucociliary transport and nasal histology [22,23,24].…”

Section: Discussionmentioning

confidence: 71%

Inhaled Ethanolic and Aqueous Solutions via Respimat Soft Mist Inhaler Are Well-Tolerated in Asthma Patients

Patel

Pavia²,

Lowe³

et al. 2006

Respiration

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Background: Respimat^® Soft Mist^™ Inhaler (SMI) is a new-generation inhaler offering improved lung deposition compared with other devices. Bronchodilators administered via Respimat SMI are preserved and stabilized with benzalkonium chloride (BAC) and ethylene diamine tetra-acetic acid (EDTA); both have been reported to cause paradoxical bronchoconstriction if a threshold dose is exceeded. Objective: The aim of this randomized, double-blind, three-period, crossover study was to establish that the safety of inhaled ethanolic and aqueous placebo solutions (containing BAC and EDTA) is equivalent to that of inhaled normal saline solution when administered to asthma patients via Respimat SMI. Methods: Thirty-seven asthma patients with airway hyper-reactivity were randomized to receive four actuations of each of the following three treatments via Respimat SMI, one on each of 3 study days: ethanolic placebo (12 µl 96% ethanol + 0.13 µg EDTA/actuation), aqueous placebo (12 µl water + 5.5 µg EDTA + 1.1 µg BAC/actuation), and normal saline (12 µl 0.9% sodium chloride/actuation). Pulmonary function tests were performed at baseline and at 5, 15, 30, 60, 120 and 180 min after inhalation; the primary endpoint was the lowest FEV₁ recorded between 0 and 30 min. Results: The mean lowest FEV₁ recorded between 0 and 30 min after inhalation minus the study day baseline was –0.090 litres for ethanolic placebo, –0.121 litres for aqueous placebo and –0.094 litres for normal saline (SEM 0.034 litres for all). The mean treatment differences were: ethanolic placebo versus normal saline 0.004 litres (90% CI –0.075–0.083 litres, p = 0.002), and aqueous placebo versus normal saline –0.028 litres (90% CI –0.107–0.052 litres, p = 0.006). Since both 90% CIs fell within the pre-determined equivalence region of ±0.15 litres, both treatments were considered equivalent to normal saline. Conclusion: Ethanolic and aqueous solutions administered via Respimat SMI are safe with regard to paradoxical bronchoconstriction in asthma patients with airway hyper-reactivity.

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Section: Discussionmentioning

confidence: 71%

Inhaled Ethanolic and Aqueous Solutions via Respimat Soft Mist Inhaler Are Well-Tolerated in Asthma Patients

Patel

Pavia²,

Lowe³

et al. 2006

Respiration

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“…Figure 4 and Table 4 show various components and mediators affecting the stimulation or inhibition of nasal mucus secretion. Upon either an extracellular stimuli or an unregulated secretion, the exocytosis of mucin occur, involving the movement of the mucin granule Cigarette smoke Stop/incoordinate 63) Clenbuterol No effect 58) Cocaine Paralize 64) Ephedrine Stimulate 65) Epinephrine Stimulate 66) Fluticasone propionate No effect 67) Guaiphenesin No effect 58) Hyoscine Inhibit 58) Insulin No effect 68,69) Ipratropium No effect 58) Lidocaine No effect 70) Menthol Inhibit 71) Methyl xanthines Stimulate Hypertonic (>1.5% NaCl) Stop 8,54) Hypotonic (<0.45% NaCl) Inhibit 8,54) Microspheres Inhibit 55) pH (>11) Inhibit 54) pH (<6) Inhibit 54) Temperature >40°C Inhibit Temperature <30°C Inhibit Viscosity (increased) Inhibit to the apical surface of the goblet cell. At the surface of the mucosa different components are mixed together and become mucus.…”

Section: Mucinmentioning

confidence: 99%

The Effect of Cilia and the Mucociliary Clearance on Successful Drug Delivery

Gizurarson

2015

Biological & Pharmaceutical Bulletin

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Nasal mucociliary clearance is one of the most important factors affecting nasal delivery of drugs and vaccines. This is also the most important physiological defense mechanism inside the nasal cavity. It removes inhaled (and delivered) particles, microbes and substances trapped in the mucus. Almost all inhaled particles are trapped in the mucus carpet and transported with a rate of 8-10 mm/h toward the pharynx. This transport is conducted by the ciliated cells, which contain about 100-250 motile cellular appendages called cilia, 0.3 µm wide and 5 µm in length that beat about 1000 times every minute or 12-15 Hz. For efficient mucociliary clearance, the interaction between the cilia and the nasal mucus needs to be well structured, where the mucus layer is a tri-layer: an upper gel layer that floats on the lower, more aqueous solution, called the periciliary liquid layer and a third layer of surfactants between these two main layers. Pharmacokinetic calculations of the mucociliary clearance show that this mechanism may account for a substantial difference in bioavailability following nasal delivery. If the formulation irritates the nasal mucosa, this mechanism will cause the irritant to be rapidly diluted, followed by increased clearance, and swallowed. The result is a much shorter duration inside the nasal cavity and therefore less nasal bioavailability.

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“…Some studies, including both in vitro and in vivo studies [3,4,5], have suggested that BKC does produce adverse effects on mucociliary activity. Other data, however, suggest BKC lacks deleterious effects [10,11,12,13]. The discrepancy in these results, particularly between in vitro and in vivo findings, could be explained by the possibility of problems in the experimental design and methodology as well as the difference between in vitro and in vivo conditions [13,14].…”

Section: Discussionmentioning

confidence: 60%

Effects of Benzalkonium Chloride and Potassium Sorbate on Airway Ciliary Activity

Deng

Han

Zhang

2012

ORL

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Objectives: Preservatives are indispensable components of aqueous multidose topical formulations. The purpose of our study was to investigate the effects of two representative preservatives, benzalkonium chloride (BKC) and potassium sorbate (PS), on rabbit tracheal ciliary beat frequency (CBF). Methods: Rabbit tracheal ciliated cell culture was established and CBF was determined using high-speed digital imaging methods. The effects of preservatives at different concentrations on CBF were observed over a 10-min exposure period. Results: BKC induced inhibition of CBF in a concentration-dependent manner. Ciliary beating was stopped by 0.01% BKC after 5 min of exposure. A low concentration of PS (0.12%) only resulted in a mild decrease in CBF during a 10-min exposure. The CBF decreased by 13.0% from baseline after 10 min. However, there was no statistically significant difference compared with the corresponding control condition. Application of 0.24, 0.48 and 0.96% of PS to rabbit tracheal cells resulted in an increase in CBF, with an increase of 105 ± 9.8, 107.6 ± 4.0, and 117.1 ± 9.5% relative to baseline CBF after 10 min of exposure, respectively. Conclusions: PS could be considered as a safer and more promising preservative than BKC for use in topical formulations.

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The lack of effect of benzalkonium chloride on the cilia of the nasal mucosa in patients with perennial allergic rhinitis: a combined functional, light, scanning and transmission electron microscopy study

Abstract: Despite reports of its ciliostatic effects in vitro, BKC did not have such an effect when it was applied for 6 weeks (with/without fluticasone propionate) to the nasal mucosa of perennial allergic rhinitis patients in vivo.

Cited by 50 publications

References 14 publications

Inhaled Ethanolic and Aqueous Solutions via Respimat Soft Mist Inhaler Are Well-Tolerated in Asthma Patients

Inhaled Ethanolic and Aqueous Solutions via Respimat Soft Mist Inhaler Are Well-Tolerated in Asthma Patients

The Effect of Cilia and the Mucociliary Clearance on Successful Drug Delivery

Effects of Benzalkonium Chloride and Potassium Sorbate on Airway Ciliary Activity

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