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Original Research |

Vicks VapoRub Induces Mucin Secretion, Decreases Ciliary Beat Frequency, and Increases Tracheal Mucus Transport in the Ferret Trachea FREE TO VIEW

Juan Carlos Abanses, MD; Shinobu Arima, MD; Bruce K. Rubin, MD, FCCP*
Author and Funding Information

*From the Department of Pediatrics, Wake Forest University School of Medicine, Winston-Salem, NC.

Correspondence to: Bruce K. Rubin, MD, MEngr, MBA, Professor and Vice Chair, Department of Pediatrics, Wake Forest University School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157-1081; e-mail: brubin@wfubmc.edu

*Values are given as the mean ± SD, unless otherwise indicated. K-Y = water-soluble jelly (K-Y Jelly; Johnson & Johnson).

The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).


The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).


Chest. 2009;135(1):143-148. doi:10.1378/chest.08-0095
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Published online

Background:  Vicks VapoRub (VVR) [Proctor and Gamble; Cincinnati, OH] is often used to relieve symptoms of chest congestion. We cared for a toddler in whom severe respiratory distress developed after VVR was applied directly under her nose. We hypothesized that VVR induced inflammation and adversely affected mucociliary function, and tested this hypothesis in an animal model of airway inflammation.

Methods:  [1] Trachea specimens excised from 15 healthy ferrets were incubated in culture plates lined with 200 mg of VVR, and the mucin secretion was compared to those from controls without VVR. Tracheal mucociliary transport velocity (MCTV) was measured by timing the movement of 4 μL of mucus across the trachea. Ciliary beat frequency (CBF) was measured using video microscopy. [2] Anesthetized and intubated ferrets inhaled a placebo or VVR that was placed at the proximal end of the endotracheal tube. We evaluated both healthy ferrets and animals in which we first induced tracheal inflammation with bacterial endotoxin (a lipopolysaccharide [LPS]). Mucin secretion was measured using an enzyme-linked lectin assay, and lung water was measured by wet/dry weight ratios.

Results:  [1] Mucin secretion was increased by 63% over the controls in the VVR in vitro group (p < 0.01). CBF was decreased by 35% (p < 0.05) in the VVR group. [2] Neither LPS nor VVR increased lung water, but LPS decreased MCTV in both normal airways (31%) and VVR-exposed airways (30%; p = 0.03), and VVR increased MCTV by 34% in LPS-inflamed airways (p = 0.002).

Conclusions:  VVR stimulates mucin secretion and MCTV in the LPS-inflamed ferret airway. This set of findings is similar to the acute inflammatory stimulation observed with exposure to irritants, and may lead to mucus obstruction of small airways and increased nasal resistance.

Figures in this Article

Vicks VapoRub (VVR) [Proctor and Gamble; Cincinnati, OH] is sometimes used to relieve symptoms of colds and congestion. The active ingredients of VVR are camphor (4.8%), menthol (2.7%), and eucalyptus oil (1.2%).1 Although these aromatics provide a sensation of increased nasal airflow, there is no improvement in airflow or decrease in nasal resistance with the use of VVR.2

Although VVR is not recommended for direct application in the nostril, and is not recommended for children < 2 years of age,1 this advice is sometimes ignored. We cared for a toddler in whom respiratory distress developed requiring hospital admission after VVR was applied directly under her nose and then conducted studies in the ferret to elucidate the probable mechanisms for this respiratory distress.

An 18-month-old previously healthy girl was brought to the emergency department (ED) by her grandparents. The grandmother stated that the girl had an upper respiratory infection but otherwise had been well until 2 h before coming to the ED when severe respiratory distress suddenly developed.

In the ED, the child was not interactive with her grandparents or the medical staff. She had wheezing and intercostal retractions. Her initial pulse oximetry saturation was 0.66 while breathing ambient air. The patient was thought to have acute asthma and was treated with inhaled oxygen by nasal cannula, 360 μg of albuterol by pressurized metered-dose inhaler and holding chamber, and 2 mg/kg IV prednisolone without a clinical response. A chest radiograph showed mild peribronchial cuffing but no infiltrates or hyperinflation. With supplemental oxygen, pulse oximetry saturation increased to 0.93. On further questioning, the grandmother spontaneously stated that VVR had been placed under the child's nostrils and respiratory distress had quickly developed over a period of 30 to 45 min. The child was taking no other medications and had no clinical evidence of an allergic response. The patient was admitted to the hospital while receiving supplemental oxygen and was discharged to home the following day. We hypothesized that the application of VVR induced inflammation and mucociliary dysfunction, with mucus hypersecretion leading to severe dyspnea. The specific aims of this study were to evaluate the effect of VVR on tracheal mucus secretion and clearance, airway inflammation, and pulmonary vascular fluid leakage in the ferret airway, with and without initial exposure to bacterial endotoxin (ie, lipopolysaccharide [LPS]), to induce acute inflammation similar to that occurring during a respiratory tract infection.

Animals

Unlike rodents, ferrets have an airway anatomy and cellular composition that is similar to humans and other carnivores, and have often been used to study airway inflammation and mucus secretion.3,4 Adult ferrets (weight, 1.0 to 1.6 kg) were obtained from Marshall Farms (Rose, NY). This study was approved by the Wake Forest University Animal Care and Use Committee.

Study 1

As a requirement for Animal Care and Use Committee approval, we first studied the effects of VVR on tracheal mucin secretion, ciliary beat frequency (CBF), and tracheal mucociliary transport velocity (MCTV) ex vivo in tracheas from 15 ferrets. Ferrets were killed using an intraperitoneal injection of pentobarbital (120 mg/kg). The trachea and lungs were removed by block dissection.

Excised tracheas were divided longitudinally from the cricoids to the carina and were allowed to rest for 30 min in Krebs-Henseleit solution (KHS) [6.9 g/L NaCl, 0.35 g/L KCl, 0.16 g/L KH2PO4, 0.141 g/L MgSO4, 0.373 g/L CaCl2, 2 g/L D-glucose, pH 7.4]. The tracheas were submerged for 30 min with either 200 mg of a water-soluble jelly (K-Y Jelly; Johnson & Johnson; New Brunswick, NJ) or VVR layered on the base of a 10-mL culture plate with 7 mL of KHS added. This was kept at ferret body temperature (38°C). Period I (basal secretion) was measured for 30 min with 7 mL of KHS alone. Period 2 (stimulated secretion) was measured for 30 min with 7 mL of KHS with either 200 mg (control) of water-soluble jelly (K-Y Jelly; McNeil-PPC, Inc; Fort Washington, PA) or 200 mg of VVR layered on the base of the plates. Mucin secretion was measured by using an enzyme-linked lectin assay. MCTV was measured by timing the movement of mucus across the trachea, and CBF was measured on this tracheal segment using fast video microscopy. We did not measure the soluble components of VVR in the KHS.

Study 2A (In Vivo, Airway Not Inflamed)

Fourteen ferrets were anesthetized with 40 mg/kg ketamine and 5 mg/kg xylazine, and were shallowly intubated with a 3.0 uncuffed endotracheal tube (ETT). The ETT was placed approximately 1 cm below the larynx, and placement was checked using a pediatric fiberoptic bronchoscope. Either water-soluble jelly (K-Y Jelly; Johnson & Johnson) [negative control] or 0.5 mg of VVR was layered on the inside of the ETT connector keeping the ETT itself (interior and exterior) free of the test agent. The volume chosen (0.5 mg) was based on the personal experience of a mother working in the laboratory of the PI who had often put VVR under her children's noses. The animals were able to breathe spontaneously with the ETT in place for 90 min and were then killed. Wet-to-dry weights of the lung, MCTV, and mucin secretion were then measured.

Study 2B (In Vivo, Airway LPS Inflamed)

To evaluate the effects of VVR in the inflamed airway, eight ferrets were intubated to the carina for 30 min with an ETT coated with either water-soluble jelly (K-Y Jelly) or 10 mg of LPS (Escherichia coli LPS serotype 0111:B4; Sigma; St. Louis, MO) mixed in 300 μL of water-soluble jelly (K-Y Jelly). The following day, VVR or control exposure was performed, and the animal was killed. Wet-to-dry weights of the lung, MCTV, and mucin secretion were then measured.

Laboratory Analyses
Pulmonary Tissue Wet/Dry Weight Ratio of Lung Water:

After killing the ferret, the trachea and lungs were removed by block dissection. The lungs were weighed, minced, and lyophilized to complete dryness in order to determine the wet/dry weight ratio as a measurement of total lung water.

Mucin Secretion:

Mucin secretion was measured using a Dolichos biflorus agglutinin (DBA) enzyme-linked lectin assay that we have previously described.3 In brief, a 96-well microtiter plate was coated with 60 μL of DBA as 6 μg/mL in phosphate-buffered saline (PBS) solution and incubated at room temperature overnight. After rinsing five times with a PBS solution containing 0.5% Tween 20 (PBS-Tween solution), the wells were then exposed to a sample at 38°C for 2 h and then incubated for 1 h with 50 μL of DBA conjugated with horseradish peroxidase (0.25 μg/mL) in PBS solution. Before and after this step, the plate was washed five times with PBS-Tween solution. Tetramethylbenzidine 0.42 mmol/L (150 μL) in a citrate-acetate buffer (pH 6.0) was added to each well and incubated for 10 min. The reaction was stopped by adding 50 μL of 4.7 nmol/L H2SO4. Color development was read as the difference in absorbance at 450 and 650 nm. The mucin concentration was calculated by comparison with porcine gastric mucin (0 to 200 ng/mL). The results were expressed as mucin weight per tissue weight (in nanograms per gram).

CBF:

CBF was measured by using a high-speed video recorder attached to a phase contrast microscope. The light shift with each ciliary beat was counted from five fields of view during slow playback, and the CBF was counted as the mean frequency. The tracheas were kept in a humidified chamber throughout the measurement.

Tracheal MCTV:

MCTV was measured by placing a tracheal segment under a microscope and recording the transport time of the leading edge of a 0.2-mg sample of mucus that was placed on the tracheal epithelium.4 A small volume of ferret tracheal mucus was collected from the outside of the ETT each time the tube was removed from the airway. This mucus was then used to measure MCTV. The time to transport the mucus 3 mm was used to calculate the MCTV (in millimeters per minute). Measurements were repeated five times for each tracheal segment.

Data Analysis

A power calculation was conducted with appropriate software (G*Power 2; University of Düsseldorf; Düsseldorf, Germany) using the increase in mucin secretion as the primary outcome measurement.5 Based on pilot data, the mean (± SD) [unconverted] mucin secretion in the ferret was 5,381 ± 1,727 OD units. After demonstrating an increase in mucin secretion with VVR in the initial in vitro experiments, an a priori analysis for a one-tailed t test of means suggested that six animals per group would detect a 50% increase in mucin secretion with α = 0.05 and power (1 − β) = 0.80 (two-tailed testing required 11 animals per group). After assuring that the data were normally distributed, comparisons of the changes in mucin, lung water, MCTV, and CBF with VVR over those in controls were made using two-tailed paired t tests for the first study where hemitracheas from each individual animal were exposed to VVR or control conditions, and by two tailed unpaired t tests for the second and third studies using different animals in each group. By convention, p values < 0.05 were accepted as statistically significant.

Mucin Secretion

In vitro (study 1) VVR increased mucin secretion by 59% over baseline (n = 15; mean relative secretory index, 2.22 ± 1.17; p = 0.0012) [Fig 1].

Figure Jump LinkFigure 1 VVR significantly increased tracheal mucin secretion in vitro (p = 0.012)Grahic Jump Location

In vivo (study 2) VVR increased mucin secretion in the normal airway (14%) and in the inflamed airway (7.8%), but this did not reach statistical significance. Mucin secretion was significantly increased by 67% in the group treated with LPS compared to the group not treated with LPS (p = 0.007), but VVR only slightly increased mucin secretion further (Fig 2).

Figure Jump LinkFigure 2 LPS significantly increased tracheal mucin secretion in vivo (p = 0.007). Mucin secretion was similar in control and VVR-exposed tracheasGrahic Jump Location
CBF

In vitro VVR application decreased the mean CBF by 36% to 6.8 ± 0.5 Hz relative to the that for control conditions (10.7 ± 1.1 Hz; p = 0.042) [Fig 3].

Figure Jump LinkFigure 3 VVR significantly decreased CBF in vivo (p = 0.042)Grahic Jump Location
Tracheal MCTV

In vitro, there was no significant difference in MCTV comparing VVR to control samples (n = 14; p = 0.10). The mean MCTV in control tracheas was 9.5 ± 3.4 mm/min compared with 10.0 ± 3.1 mm/min in VVR-exposed airways.

In vivo, LPS decreased MCTV in both control airway (31%) and VVR-exposed airways (30%), but this decrease was not significant (p = 0.10). In the noninflamed airway, VVR did not significantly change MCTV compared with control conditions (p = 0.21), but in the LPS-inflamed airway there was a 34% increase in MCTV with VVR application over the inflamed airway without VVR application (p = 0.002) [Fig 4].

Figure Jump LinkFigure 4 LPS decreased MCTV, but this was not statistically significant (p = 0.1). VVR increased MCTV (p = 0.027 for all tracheas and p = 0.007 in the LPS inflamed airway) [black bars]Grahic Jump Location
Lung Water

As shown in Table 1, neither LPS nor VVR-induced pulmonary vascular leakage (lung water, approximately 78% in all groups; p = 0.60; n = 14). There was also no difference in lung water when comparing the control and VVR lungs. The group treated with LPS had a significantly higher wet weight than the groups not treated with LPS (p = 0.008); however, the percentage of lung water remained the same, suggesting that this increase in wet weight was due to a proportionate increase in water and solids (eg, proteins and cells).

Table Graphic Jump Location
Table 1 Although LPS Significantly Increased Total Lung Weight, Neither LPS Nor VVR (or the Combination) Increased Lung Water*

*Values are given as the mean ± SD, unless otherwise indicated. K-Y = water-soluble jelly (K-Y Jelly; Johnson & Johnson).

Lunsford Richardson II and John Farris first compounded VVR in 1891 in Greensboro, NC, soon after buying the local W. C. Porter Drugstore. VVR was introduced in 1905 with the name Vick's Magic Croup Salve. The flu epidemic of 1918 increased VVR sales from $900,000 to $2.9 million in just 1 year. Procter & Gamble has since marketed VVR as, “The only thing more powerful than a mother's touch.”1

VVR is widely used to relieve symptoms of colds and congestion, but there are few data supporting a clinical benefit. In a small open-label study,6 VVR was thought to decrease restlessness in children with “acute bronchitis.” However, VVR has been reported to cause keratoconjunctivitis,7 mental status changes,8 lipoid pneumonia,9 bronchospasm, and type IV allergic reactions.10 Hepatotoxicity has been described in a case report11 of a 2-month-old infant via direct absorption of VVR through the skin, which improved when the medication was discontinued. Menthol, the major active ingredient of VVR, has demonstrated a reflex inhibition of respiration in both animals and humans.1214

VVR stimulated mucin secretion in vitro consistent with what has been reported15 during an acute inflammatory process. Similar to this study, it has been shown16 that menthol increases the amount of mucus in dogs when applied to the nasal mucosa. In vivo, we documented a 14% increase in mucin secretion in the normal airway and an 8% increase in the LPS-inflamed airway, but these differences were not statistically significant. This increase, on top of a 67% increase by LPS, may have maximized the mucus secretory capacity of the epithelium. It is not known whether this effect would be different in a child with an acute viral respiratory infection, such as the infant we described in the “Case Report” section. Increased mucus secretion can reduce the diameter of the airways. As previously reported, LPS also increased tracheal mucin secretion.3,17 However, while LPS increased the lung weight (p = 0.008), the percentage of wet lung volume compared to dry lung volume remained the same both in vitro and in vivo (78%). This increased weight could be explained by an influx of neutrophils and cells in response to airway LPS rather than to a vascular fluid leak.18In vitro, CBF was decreased, which is consistent with reports19,20 that menthol is directly ciliotoxic. In vivo, VVR increased MCTV by 34% in the inflamed airway, which is also consistent with the presence of inflammation.

The active ingredients of VVR are camphor, menthol, and eucalyptus.1 Menthol is thought to be the primary agent responsible for the sensation of decreased congestion by activating trigeminal cold receptors.21,22 Menthol binds to the TRPMA8 receptor (a temperature receptor), activating a surface pore causing calcium ions to flow into the cell, thereby lowering the external calcium concentration.23 The cold receptors respond by producing an efflux of calcium and depolarizing the membrane. The brain recognizes the depolarization as a cooling sensation and perceives it to be due to increased airflow across the nostrils despite an actual decrease in airflow.24 In the human nasal cavity, menthol increased nasal resistance within 1 min, and this persisted for 210 min despite the patients reporting a decrease in their nasal symptoms.25 Although exercise increased nasal airflow measured by rhinomanometry in 70% of healthy subjects, only 20% of these subjects perceived an increase in nasal airflow. In contrast, when VVR was placed in the nose of these same healthy subjects, 100% reported a sensation of improved airflow while the objective rhinomanometry measurement showed no increased airflow in any subject.2 Similar results have been reported in a series of studies by Eccles and colleagues.2628

There are limitations to the interpretation of these results. The most dramatic results were from the in vitro experiments where the tracheas were exposed to a higher concentration of VVR than is typically achieved in the airway. It was beyond the scope of this study to measure any possible in vitro dose response. However, our ability to detect small but potentially clinically significant changes after the inhalation of VVR vapors in the intubated ferret supports the suggestion that these changes in mucus secretion and clearance may, in part, explain what we saw in the human infant.

We were prompted to conduct these studies in the ferret because of the infant described in the “Case Report” section as well as other young children we have seen in the ED since we began routinely asking about the use of VVR in young children with acute respiratory distress. Because of the limitations in conducting clinical studies, we do not know the extent to which the results in our ferret model adequately explain the clinical difficulties experienced by some, but certainly not all, infants with VVR placed directly in their nose. It is likely that there was a neurogenic response to the VVR, which could take the form of mucus secretion, pulmonary vascular leakage, or alterations in CBF, as well as things we did not measure, including the elaboration of inflammatory mediators and bronchial smooth muscle contraction. It is also possible that reflex inhibition of respiration could lead to hypoxemia, although it is unlikely that this would produce the significant respiratory distress that we documented in this infant.

In summary, although VVR can fool the brain into perceiving increased airflow by activation of trigeminal cold receptors, the active ingredients are ciliotoxic and mildly proinflammatory, increasing mucus secretion while decreasing mucus clearance. This may be of little physiologic consequence in older children and adults, but in infants and small children this potentially can lead to respiratory distress.

CBF

ciliary beat frequency

DBA

Dolichos biflorus agglutinin

ED

emergency department

ETT

endotracheal tube

KHS

Krebs-Henseleit solution

LPS

lipopolysaccharide

MCTV

tracheal mucociliary transport velocity

PBS

phosphate-buffered saline

VVR

Vicks VapoRub

Protcor & Gamble Vicks VapoRub.Accessed December 1, 2008 Available at:http://www.vicks.com/products/vaporub.
 
Burrow A, Eccles R, Jones AS. The effects of camphor, eucalyptus and menthol vapour on nasal resistance to airflow and nasal sensation. Acta Otolaryngol. 1983;96:157-161. [PubMed] [CrossRef]
 
Kishioka C, Okamoto K, Kim JS, et al. Regulation of secretion from mucous and serous cells in the excised ferret trachea. Respir Physiol. 2001;126:163-171. [PubMed] [CrossRef]
 
Okamoto K, Kim J-S, Rubin BK. Secretory phospholipases A2 stimulate mucus secretion, induce airway inflammation, and produce secretory hyperresponsiveness to neutrophil elastase in the ferret trachea. Am J Physiol Lung Cell Mol Physiol. 2007;292:L62-L67. [PubMed] [CrossRef]
 
Faul F, Erdfelder E, Lang A-G, et al. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007;39:175-191. [PubMed] [CrossRef]
 
Berger H, Madreiter H, Jarosch E. Effect of VapoRub on the restlessness of children with acute bronchitis. J Int Med Res. 1978;6:491-493. [PubMed]
 
Jaiwal A. Vick's VapoRub induced dermokerato conjunctivitis: a case report. Indian J Ophthalmol. 1989;37:154. [PubMed]
 
Ferrando RL, McCorvey E Jr, Simon WA, et al. Bizarre behavior following the ingestion of levo-desoxyephedrine. Drug Intell Clin Pharm. 1988;22:214-217. [PubMed]
 
Gattuso P, Reddy VB, Castelli MJ. Exogenous lipoid pneumonitis due to Vicks VapoRub inhalation diagnosed by fine needle aspiration cytology. Cytopathology. 1991;2:315-316. [PubMed] [CrossRef]
 
Schaller M, Korting HC. Allergic airborne contact dermatitis from essential oils used in aromatherapy. Clin Exp Dermatol. 1995;20:143-145. [PubMed] [CrossRef]
 
Uc A, Bishop WP, Sanders KD. Camphor hepatotoxicity. South Med J. 2000;93:596-598. [PubMed]
 
McBride B, Whitelaw WA. A physiological stimulus to upper airway receptors in humans. J Appl Physiol. 1981;51:1189-1197. [PubMed]
 
Orani GP, Anderson JW, Sant'Ambrogio G, et al. Upper airway cooling and l-menthol reduce ventilation in the guinea pig. J Appl Physiol. 1991;70:2080-2086. [PubMed]
 
Sant'Ambrogio FB, Anderson JW, Sant'Ambrogio G. Menthol in the upper airway depresses ventilation in newborn dogs. Respir Physiol. 1992;89:299-307. [PubMed] [CrossRef]
 
Seybold ZV, Mariassy AT, Stroh D, et al. Mucociliary interactionin vitro: effects of physiological and inflammatory stimuli. J Pharm Pharmacol. 1994;46:618-630. [PubMed]
 
Fox N. Effects of camphor, eucalyptol, and menthol on the vascular state of the mucous membrane. Arch Otolaryngol Head Neck Surg. 1927;6:112-122. [CrossRef]
 
Harkema JR, Hotchkiss JA. In vivoeffects of endotoxin on intraepithelial mucosubstances in rat pulmonary airways: quantitative histochemistry. Am J Pathol. 1992;141:307-317. [PubMed]
 
Harkema JR, Hotchkiss JA. In vivoeffects of endotoxin on nasal epithelial mucosubstances: quantitative histochemistry. Exp Lung Res. 1991;17:743-761. [PubMed] [CrossRef]
 
Riechelmann H, Brommer C, Hinni M, Martin C. Response of human ciliated respiratory cells to a mixture of menthol, eucalyptus oil and pine needle oil. Arzneimittelforschung. 1997;47:1035-1039. [PubMed]
 
Das PK, Rathor RS, Sinha PS, et al. Effect on ciliary movements of some agents which come in contact with the respiratory tract. Indian J Physiol Pharmacol. 1970;14:297-303. [PubMed]
 
Eccles R. Menthol and related cooling compounds. J Pharm Pharmacol. 1994;46:618-630. [PubMed] [CrossRef]
 
Jones AS, Crosher R, Wight RG, et al. The effect of local anaesthesia of the nasal vestibule on nasal sensation of airflow and nasal resistance. Clin Otolaryngol. 1987;12:461-464. [PubMed] [CrossRef]
 
Jordt SC, Mckeny DD, Julius D. Lessons from pepper and peppermint: the molecular logic of thermal sensation. Curr Opin Neurobiol. 2003;13:487-492. [PubMed] [CrossRef]
 
Schafer K, Braun HA, Hensel H. Static and dynamic activity of cold receptors at various calcium levels. J Neurophysiol. 1982;47:1017-1028. [PubMed]
 
Butler DB, Ivy AC. Effects of nasal inhalers on erectile tissues of the nose. Arch Otolaryngol Head Neck Surg. 1943;38:309-317. [CrossRef]
 
Eccles R, Lancashire B, Tolley NS. The effect of aromatics on inspiratory and expiratory nasal resistance to airflow. Clin Otolaryngol. 1987;12:11-14. [PubMed] [CrossRef]
 
Eccles R, Griffiths DH, Newton CG, et al. The effects of D and L isomers of menthol upon nasal sensation of airflow. J Laryngol Otol. 1988;102:506-508. [PubMed] [CrossRef]
 
Eccles R, Griffiths DH, Newton CG, et al. The effects of menthol isomers on nasal sensation of airflow. Clin Otolaryngol. 1988;13:25-29. [PubMed] [CrossRef]
 

Figures

Figure Jump LinkFigure 1 VVR significantly increased tracheal mucin secretion in vitro (p = 0.012)Grahic Jump Location
Figure Jump LinkFigure 2 LPS significantly increased tracheal mucin secretion in vivo (p = 0.007). Mucin secretion was similar in control and VVR-exposed tracheasGrahic Jump Location
Figure Jump LinkFigure 3 VVR significantly decreased CBF in vivo (p = 0.042)Grahic Jump Location
Figure Jump LinkFigure 4 LPS decreased MCTV, but this was not statistically significant (p = 0.1). VVR increased MCTV (p = 0.027 for all tracheas and p = 0.007 in the LPS inflamed airway) [black bars]Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1 Although LPS Significantly Increased Total Lung Weight, Neither LPS Nor VVR (or the Combination) Increased Lung Water*

*Values are given as the mean ± SD, unless otherwise indicated. K-Y = water-soluble jelly (K-Y Jelly; Johnson & Johnson).

References

Protcor & Gamble Vicks VapoRub.Accessed December 1, 2008 Available at:http://www.vicks.com/products/vaporub.
 
Burrow A, Eccles R, Jones AS. The effects of camphor, eucalyptus and menthol vapour on nasal resistance to airflow and nasal sensation. Acta Otolaryngol. 1983;96:157-161. [PubMed] [CrossRef]
 
Kishioka C, Okamoto K, Kim JS, et al. Regulation of secretion from mucous and serous cells in the excised ferret trachea. Respir Physiol. 2001;126:163-171. [PubMed] [CrossRef]
 
Okamoto K, Kim J-S, Rubin BK. Secretory phospholipases A2 stimulate mucus secretion, induce airway inflammation, and produce secretory hyperresponsiveness to neutrophil elastase in the ferret trachea. Am J Physiol Lung Cell Mol Physiol. 2007;292:L62-L67. [PubMed] [CrossRef]
 
Faul F, Erdfelder E, Lang A-G, et al. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007;39:175-191. [PubMed] [CrossRef]
 
Berger H, Madreiter H, Jarosch E. Effect of VapoRub on the restlessness of children with acute bronchitis. J Int Med Res. 1978;6:491-493. [PubMed]
 
Jaiwal A. Vick's VapoRub induced dermokerato conjunctivitis: a case report. Indian J Ophthalmol. 1989;37:154. [PubMed]
 
Ferrando RL, McCorvey E Jr, Simon WA, et al. Bizarre behavior following the ingestion of levo-desoxyephedrine. Drug Intell Clin Pharm. 1988;22:214-217. [PubMed]
 
Gattuso P, Reddy VB, Castelli MJ. Exogenous lipoid pneumonitis due to Vicks VapoRub inhalation diagnosed by fine needle aspiration cytology. Cytopathology. 1991;2:315-316. [PubMed] [CrossRef]
 
Schaller M, Korting HC. Allergic airborne contact dermatitis from essential oils used in aromatherapy. Clin Exp Dermatol. 1995;20:143-145. [PubMed] [CrossRef]
 
Uc A, Bishop WP, Sanders KD. Camphor hepatotoxicity. South Med J. 2000;93:596-598. [PubMed]
 
McBride B, Whitelaw WA. A physiological stimulus to upper airway receptors in humans. J Appl Physiol. 1981;51:1189-1197. [PubMed]
 
Orani GP, Anderson JW, Sant'Ambrogio G, et al. Upper airway cooling and l-menthol reduce ventilation in the guinea pig. J Appl Physiol. 1991;70:2080-2086. [PubMed]
 
Sant'Ambrogio FB, Anderson JW, Sant'Ambrogio G. Menthol in the upper airway depresses ventilation in newborn dogs. Respir Physiol. 1992;89:299-307. [PubMed] [CrossRef]
 
Seybold ZV, Mariassy AT, Stroh D, et al. Mucociliary interactionin vitro: effects of physiological and inflammatory stimuli. J Pharm Pharmacol. 1994;46:618-630. [PubMed]
 
Fox N. Effects of camphor, eucalyptol, and menthol on the vascular state of the mucous membrane. Arch Otolaryngol Head Neck Surg. 1927;6:112-122. [CrossRef]
 
Harkema JR, Hotchkiss JA. In vivoeffects of endotoxin on intraepithelial mucosubstances in rat pulmonary airways: quantitative histochemistry. Am J Pathol. 1992;141:307-317. [PubMed]
 
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    Print ISSN: 0012-3692
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