Nasal spirometry has been used previously to monitor the nasal cycle. Asymmetry of nasal airflow ... more Nasal spirometry has been used previously to monitor the nasal cycle. Asymmetry of nasal airflow is expressed as a nasal partitioning ratio (NPR) that ranges from -1 (left nasal cavity obstruction) to + (right nasal cavity obstruction) with 0 indicating symmetry of airflow. This study investigated the normal range of NPR in the decongested nose as a means of assessing the degree of nasal septal deviation. NPR was measured in 100 healthy volunteers using a portable spirometer. Mean NPR before decongestion was -0.1 +/- 0.32 SD (range, -0.84-0.75), and after decongestion mean NPR was -0.02 +/- 0.16 SD (range, -0.46-0.51). Male NPR ranged from -0.46 to 0.51 (mean, -0.1 +/- 0.22) whereas female NPR was from -0.21 to 0.37 (mean, -0.03 +/- 0.1; p < 0.001). There was a significant correlation between the clinicians assessment of the degree of septal deviation and NPR, r(s) = 0.69 (p < 0.01). The 95% reference range for NPR in this normal population was found to be between +0.30 and -0.34. A normal range of NPR may prove useful in assessing patients complaining of nasal obstruction. A case may be made that patients on the waiting list that fall within the normal range of NPR are unlikely to benefit from septal surgery because their nasal passages are not greatly asymmetrical.
Nasal challenge with bradykinin has been previously reported to cause sore throat. The aim of the... more Nasal challenge with bradykinin has been previously reported to cause sore throat. The aim of the present study was to investigate the mechanism of sore throat by comparing the effects of nasal and oropharyngeal challenge with bradykinin on the sensation of sore throat. Twelve healthy volunteers (6 male, 6 female, mean age 29.9 years), were given nasal followed by oropharyngeal challenge with bradykinin. The nasal and oropharyngeal challenges were separated by 1 week and 1 mg of bradykinin dissolved in 10% ethanol in 0.9% saline was administered as a spray to both nasal passages or to the posterior oropharyngeal wall and tonsillar fauces. The same group of volunteers were also given a control nasal challenge with the ethanol/saline vehicle. Subjects were asked to score symptoms of throat irritation using a ten point visual analogue scale with the extremes labelled 'Worst ever throat irritation' and 'No throat irritation', before and at intervals after bradykinin challenge. Nasal challenge with vehicle did not cause any throat irritation, but both nasal and oropharyngeal challenge with bradykinin caused a significant increase in throat irritation scores at 5 and 15 min following challenge when compared with baseline scores. At 30 min following challenge, the throat irritation scores obtained on nasal challenge were significantly greater than those obtained on oropharyngeal challenge. The results demonstrate that nasal challenge with bradykinin causes a sensation of sore throat which is just as intense as that caused by oropharyngeal challenge and with the sensation of sore throat persisting for a longer period on nasal challenge when compared with oropharyngeal challenge.(ABSTRACT TRUNCATED AT 250 WORDS)
Current Medical Research and Opinion, Feb 12, 2010
Common cold is one of the most prevalent conditions that family doctors encounter. One of the fir... more Common cold is one of the most prevalent conditions that family doctors encounter. One of the first symptoms to occur is nasal congestion, which can have a negative impact on daily life and prompts many patients to seek treatment for relief. Xylometazoline nasal spray (Otrivin*) is a topical decongestant that has been used successfully for many years and is generally recognized as an effective and safe therapy. However, most studies have investigated its clinical efficacy in healthy patients and few have included patients with common cold. To review the published clinical efficacy and safety of xylometazoline alone and in combination in the management of nasal congestion in patients with common cold. Literature searches of PubMed and the Cochrane Library were conducted to obtain published open or blinded, randomized, placebo- or active-controlled studies on the use of xylometazoline hydrochloride for the symptomatic relief of nasal congestion in patients with common cold. Searches included papers published in English only, up to September 2009. Despite the small number of studies identified in common cold (n = 4), as per search criteria defined, intranasal xylometazoline quickly and effectively relieved nasal congestion. When used alone, xylometazoline had a clinically relevant decongestant effect that was significantly superior for up to 10 hours compared with placebo. The superior decongestant effect with xylometazoline led to high patient satisfaction with treatment. When used in combination with ipratropium bromide, nasal congestion and rhinorrhoea were treated simultaneously, leading to significantly higher patient general impression scores compared with either agent used alone. Xylometazoline was well tolerated, with generally mild to moderate nasal-related side effects (e.g. epistaxis in 3.4% of patients, and blood-tinged mucus in 10-26% of patients) that were easily resolved; the most frequently reported non-nasal AEs were headache (3.4%) and period pain (10.3%); no cases of sedation were reported. As expected, no rhinitis medicamentosa or rebound congestion was noted with short-term use (<10 days). No clinically important differences in ciliary motility and mucociliary clearance were observed. Xylometazoline does not result in sympathomimetic systemic side effects seen with oral decongestants (e.g. pseudoephedrine, phenylephrine). The few studies available in common cold suggest that intranasal xylometazoline provides fast and effective relief of nasal congestion and is well tolerated. When xylometazoline is used in combination with ipratropium, patients with common cold experience the additive benefit of nasal congestion and rhinorrhoea being treated simultaneously.
Nitric oxide (NO) is known to play a role in the non-specific host defence mechanism. Furthermore... more Nitric oxide (NO) is known to play a role in the non-specific host defence mechanism. Furthermore, it has been proposed that NO may be important in respiratory defence against the viruses which cause the common cold. Indeed, elevated NO levels have previously been observed in orally expired air during upper respiratory tract infection (URTI). We wanted to investigate further the role of NO in the host response to URTI. Total nasal airway resistance (tNAR) and nasal NO levels were obtained during symptomatic URTI in 97 subjects. Of these, 80 received treatment with either oxymetazoline or a placebo spray. Post-treatment tNAR and NO levels were obtained 60 min after treatment. Measurements of NO were also repeated 4-6 weeks later, when subjects were healthy, (n = 82). NO levels were measured using a chemiluminescence gas analyse whilst tNAR was measured using posterior rhinomanometry. The mean pre-treatment NO level (1063 +/- 541 ppb) was shown to be reduced significantly after treatment with oxymetazoline (827 +/- 373ppb), p < 0.0001. The mean pre-treatment tNAR, 0.42 Pa cm-3 sec-1, was also reduced significantly to 0.21 Pa cm-1 sec-1 (p < 0.001) after treatment with oxymetazoline. There was no significant correlation between the change in NO levels and change in tNAR following treatment with oxymetazoline (p. corrected for ties = 0.011, p = 0.98. No significant difference was found between NO levels obtained during URTI (1130 +/- 444 ppb) when compared to values obtained when healthy (1197 +/- 361 ppb), p = 0.25. These results demonstrate that treatment with a topical nasal decongestant spray causes a reduction in nasal NO levels. We propose that this occurs as an indirect consequence of the vasoconstrictor actions of oxymetazoline. Since no change in NO levels was observed during URTI, we propose that the NO synthase responsible for NO production in the nose responds in a different manner to that in the lungs.
The resistance to air flow of each nasal passage was recorded in 2 subjects over a period of 7 da... more The resistance to air flow of each nasal passage was recorded in 2 subjects over a period of 7 days. The cyclical changes in nasal resistance observed were very regular, with a consistent pattern apparent over the period of study. The regular changes in nasal resistance recorded under laboratory conditions may be directly related to changes in activity of an autonomic centre in the brain.
Presents a letter to the editor about an article in the "British Medical Journal" that ... more Presents a letter to the editor about an article in the "British Medical Journal" that discussed the effects of fluid intake on the course of acute respiratory infections.
Lysozyme is a protein secreted by nasal submucosal glands. Its secretion is under cholinergic con... more Lysozyme is a protein secreted by nasal submucosal glands. Its secretion is under cholinergic control. It is considered important in nasal defence as it enzymatically hydrolyses peptidoglycan bonds in bacterial cell walls and has specific activity against Gram-positive bacteria in vitro. Oxymetazoline is freely available as a non-prescription nasal decongestant. Some recent work has shown that it has no effect on histamine-induced plasma exudation but little is known about its effects on glandular secretion. The current study is a randomized controlled study that investigates the effect of topical oxymetazoline on the total protein and lysozyme content of nasal fluid. Thirty healthy volunteers were randomized to receive either a normal saline nasal spray (placebo) or an active spray of oxymetazoline, 0.05% (w/v) in saline. NAR was assessed in all subjects using posterior rhinomanometry and nasal lavage before the application of the spray and again 10 min later. The results were analysed using non-parametric statistics. There was a significant decrease in both the lysozyme and total protein content of nasal lavage after application of oxymetazoline when compared with placebo (p < 0.05). A possible mechanism for the observed decease in total protein and lysozyme would be that the vasoconstrictor effects of oxymetazoline also apply to the vessels supplying nasal submucosal glands and that this decrease in blood supply is reflected by a decrease in secretion.
The effects of sucking a lozenge containing 11 mg L-menthol on reaction time and nasal sensation ... more The effects of sucking a lozenge containing 11 mg L-menthol on reaction time and nasal sensation were investigated in a double blind trial on 60 subjects suffering from the common cold. Reaction time was determined by measuring the response time to a stimulus presented on a microcomputer screen and nasal sensation was scored on a visual analogue scale. Menthol ingestion compared to placebo caused a significant increase in nasal sensation of airflow which persisted for up to 30 min. The simple and choice reaction times measured before ingestion of the lozenge were similar to those found in healthy uninfected subjects and there was no change in reaction time after ingestion of menthol.
The objective of this study was to determine the effects of a placebo treatment on cough in patie... more The objective of this study was to determine the effects of a placebo treatment on cough in patients with cough associated with acute upper respiratory tract infection (URTI). Patients with dry or slightly productive cough associated with a history of URTI were recruited. Cough frequency (CF) over 15 minutes was recorded by means of a microphone connected to a pen recorder. Cough suppression time (CST) was recorded when patients were instructed by means of a red light to try not to cough. Patients received either a single dose of vitamin E (placebo treatment) or no treatment. CF and CST were recorded before and 15 minutes after treatment. Twenty-seven patients were randomized to placebo treatment and 27 to the no-treatment group (mean age 22.6 years). The median difference between post- and pretreatment CF was -3 in the no-treatment group and -18 in the placebo group (p = .0003). There was a significant increase in CST in the placebo group compared with no treatment (p = .027). The results demonstrate that placebo treatment has significant antitussive activity. This placebo effect may be related to generation of central neurotransmitters such as endogenous opioids.
Nasal spirometry has been used previously to monitor the nasal cycle. Asymmetry of nasal airflow ... more Nasal spirometry has been used previously to monitor the nasal cycle. Asymmetry of nasal airflow is expressed as a nasal partitioning ratio (NPR) that ranges from -1 (left nasal cavity obstruction) to + (right nasal cavity obstruction) with 0 indicating symmetry of airflow. This study investigated the normal range of NPR in the decongested nose as a means of assessing the degree of nasal septal deviation. NPR was measured in 100 healthy volunteers using a portable spirometer. Mean NPR before decongestion was -0.1 +/- 0.32 SD (range, -0.84-0.75), and after decongestion mean NPR was -0.02 +/- 0.16 SD (range, -0.46-0.51). Male NPR ranged from -0.46 to 0.51 (mean, -0.1 +/- 0.22) whereas female NPR was from -0.21 to 0.37 (mean, -0.03 +/- 0.1; p < 0.001). There was a significant correlation between the clinicians assessment of the degree of septal deviation and NPR, r(s) = 0.69 (p < 0.01). The 95% reference range for NPR in this normal population was found to be between +0.30 and -0.34. A normal range of NPR may prove useful in assessing patients complaining of nasal obstruction. A case may be made that patients on the waiting list that fall within the normal range of NPR are unlikely to benefit from septal surgery because their nasal passages are not greatly asymmetrical.
Nasal challenge with bradykinin has been previously reported to cause sore throat. The aim of the... more Nasal challenge with bradykinin has been previously reported to cause sore throat. The aim of the present study was to investigate the mechanism of sore throat by comparing the effects of nasal and oropharyngeal challenge with bradykinin on the sensation of sore throat. Twelve healthy volunteers (6 male, 6 female, mean age 29.9 years), were given nasal followed by oropharyngeal challenge with bradykinin. The nasal and oropharyngeal challenges were separated by 1 week and 1 mg of bradykinin dissolved in 10% ethanol in 0.9% saline was administered as a spray to both nasal passages or to the posterior oropharyngeal wall and tonsillar fauces. The same group of volunteers were also given a control nasal challenge with the ethanol/saline vehicle. Subjects were asked to score symptoms of throat irritation using a ten point visual analogue scale with the extremes labelled 'Worst ever throat irritation' and 'No throat irritation', before and at intervals after bradykinin challenge. Nasal challenge with vehicle did not cause any throat irritation, but both nasal and oropharyngeal challenge with bradykinin caused a significant increase in throat irritation scores at 5 and 15 min following challenge when compared with baseline scores. At 30 min following challenge, the throat irritation scores obtained on nasal challenge were significantly greater than those obtained on oropharyngeal challenge. The results demonstrate that nasal challenge with bradykinin causes a sensation of sore throat which is just as intense as that caused by oropharyngeal challenge and with the sensation of sore throat persisting for a longer period on nasal challenge when compared with oropharyngeal challenge.(ABSTRACT TRUNCATED AT 250 WORDS)
Current Medical Research and Opinion, Feb 12, 2010
Common cold is one of the most prevalent conditions that family doctors encounter. One of the fir... more Common cold is one of the most prevalent conditions that family doctors encounter. One of the first symptoms to occur is nasal congestion, which can have a negative impact on daily life and prompts many patients to seek treatment for relief. Xylometazoline nasal spray (Otrivin*) is a topical decongestant that has been used successfully for many years and is generally recognized as an effective and safe therapy. However, most studies have investigated its clinical efficacy in healthy patients and few have included patients with common cold. To review the published clinical efficacy and safety of xylometazoline alone and in combination in the management of nasal congestion in patients with common cold. Literature searches of PubMed and the Cochrane Library were conducted to obtain published open or blinded, randomized, placebo- or active-controlled studies on the use of xylometazoline hydrochloride for the symptomatic relief of nasal congestion in patients with common cold. Searches included papers published in English only, up to September 2009. Despite the small number of studies identified in common cold (n = 4), as per search criteria defined, intranasal xylometazoline quickly and effectively relieved nasal congestion. When used alone, xylometazoline had a clinically relevant decongestant effect that was significantly superior for up to 10 hours compared with placebo. The superior decongestant effect with xylometazoline led to high patient satisfaction with treatment. When used in combination with ipratropium bromide, nasal congestion and rhinorrhoea were treated simultaneously, leading to significantly higher patient general impression scores compared with either agent used alone. Xylometazoline was well tolerated, with generally mild to moderate nasal-related side effects (e.g. epistaxis in 3.4% of patients, and blood-tinged mucus in 10-26% of patients) that were easily resolved; the most frequently reported non-nasal AEs were headache (3.4%) and period pain (10.3%); no cases of sedation were reported. As expected, no rhinitis medicamentosa or rebound congestion was noted with short-term use (<10 days). No clinically important differences in ciliary motility and mucociliary clearance were observed. Xylometazoline does not result in sympathomimetic systemic side effects seen with oral decongestants (e.g. pseudoephedrine, phenylephrine). The few studies available in common cold suggest that intranasal xylometazoline provides fast and effective relief of nasal congestion and is well tolerated. When xylometazoline is used in combination with ipratropium, patients with common cold experience the additive benefit of nasal congestion and rhinorrhoea being treated simultaneously.
Nitric oxide (NO) is known to play a role in the non-specific host defence mechanism. Furthermore... more Nitric oxide (NO) is known to play a role in the non-specific host defence mechanism. Furthermore, it has been proposed that NO may be important in respiratory defence against the viruses which cause the common cold. Indeed, elevated NO levels have previously been observed in orally expired air during upper respiratory tract infection (URTI). We wanted to investigate further the role of NO in the host response to URTI. Total nasal airway resistance (tNAR) and nasal NO levels were obtained during symptomatic URTI in 97 subjects. Of these, 80 received treatment with either oxymetazoline or a placebo spray. Post-treatment tNAR and NO levels were obtained 60 min after treatment. Measurements of NO were also repeated 4-6 weeks later, when subjects were healthy, (n = 82). NO levels were measured using a chemiluminescence gas analyse whilst tNAR was measured using posterior rhinomanometry. The mean pre-treatment NO level (1063 +/- 541 ppb) was shown to be reduced significantly after treatment with oxymetazoline (827 +/- 373ppb), p < 0.0001. The mean pre-treatment tNAR, 0.42 Pa cm-3 sec-1, was also reduced significantly to 0.21 Pa cm-1 sec-1 (p < 0.001) after treatment with oxymetazoline. There was no significant correlation between the change in NO levels and change in tNAR following treatment with oxymetazoline (p. corrected for ties = 0.011, p = 0.98. No significant difference was found between NO levels obtained during URTI (1130 +/- 444 ppb) when compared to values obtained when healthy (1197 +/- 361 ppb), p = 0.25. These results demonstrate that treatment with a topical nasal decongestant spray causes a reduction in nasal NO levels. We propose that this occurs as an indirect consequence of the vasoconstrictor actions of oxymetazoline. Since no change in NO levels was observed during URTI, we propose that the NO synthase responsible for NO production in the nose responds in a different manner to that in the lungs.
The resistance to air flow of each nasal passage was recorded in 2 subjects over a period of 7 da... more The resistance to air flow of each nasal passage was recorded in 2 subjects over a period of 7 days. The cyclical changes in nasal resistance observed were very regular, with a consistent pattern apparent over the period of study. The regular changes in nasal resistance recorded under laboratory conditions may be directly related to changes in activity of an autonomic centre in the brain.
Presents a letter to the editor about an article in the "British Medical Journal" that ... more Presents a letter to the editor about an article in the "British Medical Journal" that discussed the effects of fluid intake on the course of acute respiratory infections.
Lysozyme is a protein secreted by nasal submucosal glands. Its secretion is under cholinergic con... more Lysozyme is a protein secreted by nasal submucosal glands. Its secretion is under cholinergic control. It is considered important in nasal defence as it enzymatically hydrolyses peptidoglycan bonds in bacterial cell walls and has specific activity against Gram-positive bacteria in vitro. Oxymetazoline is freely available as a non-prescription nasal decongestant. Some recent work has shown that it has no effect on histamine-induced plasma exudation but little is known about its effects on glandular secretion. The current study is a randomized controlled study that investigates the effect of topical oxymetazoline on the total protein and lysozyme content of nasal fluid. Thirty healthy volunteers were randomized to receive either a normal saline nasal spray (placebo) or an active spray of oxymetazoline, 0.05% (w/v) in saline. NAR was assessed in all subjects using posterior rhinomanometry and nasal lavage before the application of the spray and again 10 min later. The results were analysed using non-parametric statistics. There was a significant decrease in both the lysozyme and total protein content of nasal lavage after application of oxymetazoline when compared with placebo (p < 0.05). A possible mechanism for the observed decease in total protein and lysozyme would be that the vasoconstrictor effects of oxymetazoline also apply to the vessels supplying nasal submucosal glands and that this decrease in blood supply is reflected by a decrease in secretion.
The effects of sucking a lozenge containing 11 mg L-menthol on reaction time and nasal sensation ... more The effects of sucking a lozenge containing 11 mg L-menthol on reaction time and nasal sensation were investigated in a double blind trial on 60 subjects suffering from the common cold. Reaction time was determined by measuring the response time to a stimulus presented on a microcomputer screen and nasal sensation was scored on a visual analogue scale. Menthol ingestion compared to placebo caused a significant increase in nasal sensation of airflow which persisted for up to 30 min. The simple and choice reaction times measured before ingestion of the lozenge were similar to those found in healthy uninfected subjects and there was no change in reaction time after ingestion of menthol.
The objective of this study was to determine the effects of a placebo treatment on cough in patie... more The objective of this study was to determine the effects of a placebo treatment on cough in patients with cough associated with acute upper respiratory tract infection (URTI). Patients with dry or slightly productive cough associated with a history of URTI were recruited. Cough frequency (CF) over 15 minutes was recorded by means of a microphone connected to a pen recorder. Cough suppression time (CST) was recorded when patients were instructed by means of a red light to try not to cough. Patients received either a single dose of vitamin E (placebo treatment) or no treatment. CF and CST were recorded before and 15 minutes after treatment. Twenty-seven patients were randomized to placebo treatment and 27 to the no-treatment group (mean age 22.6 years). The median difference between post- and pretreatment CF was -3 in the no-treatment group and -18 in the placebo group (p = .0003). There was a significant increase in CST in the placebo group compared with no treatment (p = .027). The results demonstrate that placebo treatment has significant antitussive activity. This placebo effect may be related to generation of central neurotransmitters such as endogenous opioids.
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Papers by Ronald Eccles