R. Eccles

Voluntary suppression of cough induced by inhalation of capsaicin in healthy volunteers

The aim of the present study was to investigate the voluntary suppression of cough in response to capsaicin inhalation in healthy volunteers, and to determine if the dose-response curve to capsaicin was significantly altered when volunteers were asked to suppress their cough response. The quantification of the degree of voluntary suppression of induced cough could provide a new methodology for screening antitussive agents as antitussives may act by influencing voluntary control of cough. Cough was induced by inhalation of capsaicin. Two challenges were given 5 min apart, each comprising five ascending concentrations of capsaicin (1 x 10(-5) M-3.33 x 10(-4) M). During one of these challenges the volunteer was allowed to cough when required, and during the other they were asked to suppress cough. These two conditions were given in random order. The cough response was recorded by means of a microphone with the integrated sound trace displayed on a chart recorder. A dose-response relationship was obtained on administration of ascending concentrations of capsaicin. In the non-suppressed challenge 23/24 subjects coughed on inhalation of capsaicin (3.33 x 10(-4) M) with a mean number of coughs of 2.92 +/- 0.34, whereas in the suppressed challenge only 3/24 subjects coughed with a mean number of coughs of 0.29 +/- 0.18 (P < 0.001). These results demonstrate that cough induced by inhalation of capsaicin can be voluntarily suppressed. The mechanism of voluntary suppression of cough is discussed in relation to capsaicin challenge and the screening of antitussive medications.

Lack of effect of codeine in the treatment of cough associated with acute upper respiratory tract infection

Codeine is often used as a standard antitussive against which new antitussives are compared. However there is little information available about the effects of codeine on cough associated with upper respiratory tract infection. The present study investigated the effects of codeine syrup B.P. (30 mg/10 ml, q.d.s.) or syrup vehicle on cough frequency and the subjective severity of cough during a 3‐h laboratory phase and a 4‐day home phase of treatment. Cough frequency and subjective scores of cough severity were significantly decreased during the 3‐h laboratory phase but at no time point was there a significant difference between the codeine‐ and placebo‐treated groups. The results of the 4‐day home phase diary were similar to those of the laboratory phase as at no time point was there a significant difference between the mean scores for the codeine‐ and placebo‐treated groups. The results indicate that codeine, either as a single 30‐mg dose or in a total daily dose of 120 mg, is no more effective than the syrup vehicle in controlling cough associated with acute upper respiratory tract infection.

The opioid agonist codeine and antagonist naltrexone do not affect voluntary suppression of capsaicin induced cough in healthy subjects

Opioids exert an analgesic action by mimicking the effects of endogenous neurotransmitter substances in the central nervous system. Opioids are widely used as antitussives, and it is reasonable to assume that endogenous opioids are involved in the control of cough. In order to investigate this hypothesis, a parallel design study was carried out to examine the effects of 50 mg codeine (opioid agonist), 50 mg naltrexone (opioid antagonist) and placebo on capsaicin-induced cough in 80 healthy volunteers (mean age 25 yrs). Volunteers received two capsaicin challenge units (each consisting of five inhalations of different concentrations of capsaicin, 0.00-3.33 x 10(-4) M). On one challenge unit subjects were instructed to suppress cough, and on the other challenge unit subjects coughed freely. Coughs were recorded on a tape cassette player and later played back into a pen recorder to produce integrated sound traces. The number of coughs in the suppression challenge unit was significantly reduced in all three treatment groups compared to that recorded in the non-suppression challenge unit. Comparisons between the three treatment groups showed that there was no statistical difference between the three groups both before and 90 min after treatment for the total coughs in the suppression challenge unit and for the total coughs in the non-suppression challenge unit. These results demonstrate that capsaicin-induced cough can be voluntarily suppressed, but that both suppressed and non-suppressed cough were unaffected by treatment with codeine, naltrexone or placebo. These results do not provide any support for the hypothesis that capsaicin-induced cough is influenced by endogenous opioid substances.

The Relationship Between Nasalance and Nasal Resistance to Airflow

The relationship between nasal airway resistance and nasalance in healthy volunteers and in subjects suffering from symptoms of acute rhinitis was investigated. A non-invasive objective measure of nasalance using the Nasometer (Kay Electronics) was used and an inverse correlation between airway resistance and nasalance was found (r = 0.67, r2 = 0.46, p less than 0.0001). The effect of a topical nasal decongestant on nasal airway resistance and nasalance was investigated, and significant changes were seen both in resistance and nasalance (p less than 0.0001) with a correlation in the changes seen in both parameters (r = 0.82, r2 = 0.66, p less than 0.0001). The measure of nasalance may be useful in assessing various forms of nasal treatment including nasal, adenoidal and palatal surgery. The measurement of nasalance is well tolerated by subjects of all ages and is particularly useful in subjects with high nasal resistance where rhinomanometry tends to be unstable.

The Relationship Between Nasal Airway Resistance and Middle Ear Pressure in Subjects with Acute Upper Respiratory Tract Infection

Middle ear pressure and nasal airway resistance were measured over 7 1/2h in 8 subjects (age 18-32) with symptomatic acute upper respiratory tract infection. The mean middle ear pressure was -13 +/- 1.5 daPa (s.e.m.) with a range between 65 to -140 daPa. The mean total nasal resistance was 0.4 +/- 0.02 Pa/cm3/s (s.e.m.) with a range between 0.20 to 1.28 Pa/cm3/s. Unilateral nasal airway resistance exhibited reciprocal fluctuations with a range between 0.18-3.60 Pa/cm3/s. The mean difference between the highest and lowest unilateral nasal resistance values for each subject was 1.48 +/- 0.22 Pa/cm3/s (n = 16). No correlation was found between unilateral nasal airway resistance and middle ear pressure. Total nasal airway resistance had an inverse correlation with middle ear pressure r = 0.32, r2 = 0.11, n = 176 (p < 0.001). The results indicate that the generation of a negative middle ear pressure in acute upper respiratory tract infection occurred in a manner consistent with intermittent obstruction of the Eustachian tube and gradual middle ear gas absorption. Rapid increases in middle ear pressure and the generation of a positive middle ear pressure were associated with nose blowing. No evidence was found to support the hypothesis that negative middle ear pressures are associated with sniffing.

Cyclical changes in nasal airway resistance and middle ear pressures.

The relationship between unilateral changes in nasal airway resistance and the ipsilateral middle ear pressure were investigated in 8 otologically and rhinologically normal adults over the course of 7 1/2 h under laboratory conditions. Despite mean changes in unilateral nasal resistance of 0.75 Pa/cm3/s associated with the nasal cycle, no correlation existed with changes in ipsilateral Eustachian tube function, as judged by serial middle ear pressure recordings (r = 0.06, r2 = 0.00, p = 0.461). Middle ear pressure in healthy adults in a controlled environment remained very constant (mean = -6.71 +/- 0.52 daPa). 69% of middle ear pressures were equal to or above 0 daPa, which represents evidence in favour of a net positive production of middle ear gas.

The Effect of Postural Change and Upper Respiratory Tract Infection on Middle Ear Pressure

The effect of a change in posture from sitting erect to lying supine and horizontal on middle ear pressure was investigated in 5 healthy adults and 5 adults with symptoms of an acute upper respiratory tract infection (URTI). The change in posture had no significant effect on middle ear pressure in the healthy subjects (p greater than 0.05). In those with URTI mean middle ear pressure increased from -39.5 daPa (erect) to -16.9 daPa (supine) (p = 0.026, n = 10). In the supine posture the middle ear pressure in subjects with URTI was raised. The cause of the increase in middle ear pressure is discussed in terms that the postural change may alter middle ear physiology such that in the supine posture there is a net production of middle ear gas as opposed to a net reabsorption in the erect posture. This may indicate that an increase in jugular venous pressure causes a net positive production of middle ear gas.

The Effect of Pressure and Warmth Applied to the Axilla on Unilateral Nasal Airway Resistance and Facial Skin Temperature

The effect of pressure, warmth, and control stimuli applied to the axilla and lateral chest wall on unilateral nasal airway resistance and facial skin temperature was investigated in 60 healthy adults. Nasal resistance was measured by posterior rhinomanometry and skin temperature with an infrared thermometer. A significant increase in unilateral nasal resistance ipsilateral to the applied stimulus was seen with both pressure and warmth (p = 0.006, p = 0.02). A decrease in unilateral nasal resistance contralateral to the stimulus was seen in both these groups, but this was not significant (p = 0.45, p = 0.81). The control stimulus showed a non-significant increase in unilateral nasal resistance ipsilateral to the applied stimulus (p = 0.55), and a significant rise in unilateral nasal resistance on the contralateral side (p = 0.008). There were no significant differences between the ipsilateral and contralateral facial skin temperatures before or after the application of a unilateral pressure, warm or control stimulus. A significant bilateral increase in facial temperature was observed during the course of the experiment in all three groups. The mechanisms of induced changes in unilateral nasal resistance are discussed. The results increase our knowledge of the corporo-nasal reflex and demonstrate that the reciprocal changes in sympathetic tone to the nasal capacitance blood vessels are independent from any parallel reflex changes in sympathetic tone to cutaneous blood vessels.

Depletion of urate in human nasal lavage following in vitro ozone exposure

Ozone, a strong oxidant present in summer smog, is thought to primarily react with antioxidant molecules found in the epithelial lining fluid of the respiratory tract. In humans, as much as 40% of inhaled ozone can be removed in the nasal cavity where the major extracellular antioxidant has been identified as uric acid. The present study was undertaken to examine urate/oxidant interactions in human nasal lavage fluid following in vitro exposure to ozone at concentrations relevant to the U.K. Lavage fluid was collected from 8 volunteers using a modified Foley catheter which permits prolonged contact of isotonic saline with the anterior nasal cavity. Nasal lavage samples in multiwell plates were exposed to ozone at concentrations of 50, 100 and 250 ppb. Samples were removed at intervals from 15 to 240 min following exposure and assayed for uric acid depletion. Uric acid concentrations in the nasal lavage were found to fall from 8.52 (time zero) to 3.99 microM, 0.05 and 0.07 microM after 240 min at 50, 100 and 250 ppb ozone respectively. At a non-environmentally relevant ozone concentration of 1000 ppb, uric acid was completely depleted after 60 min. Regression analysis showed a linear correlation between rate of loss of urate and ozone concentration (R2 = 0.97). A novel, non-invasive technique is described to investigate antioxidant compromise and its importance in individual subjects. We conclude that uric acid in nasal lavage samples is scavenged by ozone in a dose and time dependent manner.