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Background:Many over-the-counter medications are available to treat common cold nasal symptoms, but patients may be unsure which one to use. Methods:This review assesses two widely used intranasal treatments for nasal congestion and rhinorrhea in the common cold: xylometazoline hydrochloride and ipratropium bromide. Results:Xylometazoline quickly and effectively relieves nasal congestion, while ipratropium is effective at reducing rhinorrhea. When used in combination, a novel approach to treatment, nasal congestion and rhinorrhea are treated simultaneously, providing effective relief from two of the most troublesome symptoms of the common cold Both drugs are well tolerated, with only mild to moderate, nasal-related side effects. Conclusions:The efficacy and safety of the combination product suggest that it should be used first-line in the symptomatic relief of nasal congestion and rhinorrhea, before the use of oral treatments.

ABSTRACTObjective:This study compared the efficacy of 1000 mg of paracetamol combined with 60 mg of pseudoephedrine, with that of either paracetamol or pseudoephedrine alone and placebo for the treatment of symptomatic URTI.Research design and methods:A double‐blind, parallel group study was performed on 305 patients with URTI (nasal airflow resistance [NAR] of > 0.25 Pa cm3s and a global pain score of at least moderate intensity). NAR and pain relief/intensity scores were measured over 4 h after initial dose. Patients then dosed up to three times daily for 3 days and recorded nasal congestion and pain intensity scores.Main outcome measures:Nasal airflow conductance (NAC) and pain relief after the initial dose were primary objectives. NAC was calculated from NAR. Pain relief was measured on a 5‐point verbal rating scale (VRS) and pain intensity and nasal congestion on a 4‐point VRS. Data were analysed using analysis of covariance. Safety was assessed by adverse events.Results:A single dose of the combination was superior to paracetamol and placebo for NAC ( p= 0.0001) and was superior to pseudoephedrine and placebo for pain relief ( p≤ 0.048). Multiple doses of the combination were also superior to paracetamol and placebo for decongestion ( p≤ 0.021) and were superior to pseudoephedrine and placebo for pain reduction ( p≤ 0.0057). All treatments were well tolerated.Conclusions:The combination treatment provided a greater decongestant effect than either paracetamol or placebo and better pain relief than either pseudoephedrine or placebo. The additive effect of the combination was apparent for both single and multiple doses.

The article provides the clinician with core information about the aetiology and treatment of nasal congestion and discusses nasal blood vessels, autonomic nerves, nasal cycle, effects of posture, subjective sensation of congestion, objective assessments of congestion and medical and surgical treatments.

Dextromethorphan is one of the most widely used antitussives for the treatment of cough associated with acute upper respiratory tract infection. However, there is very little data to support the efficacy of dextromethorphan in this disease state. This aim of this study was to obtain more information about the efficacy of a single dose of 30 mg dextromethorphan in the treatment of cough associated with acute upper respiratory tract infection.

Objectives To assess the frequency and severity of coughing and choking episodes, possible related factors, and their association with chest infections in patients with motor neuron disease (MND). Methods Thirty seven patients with MND and 23 healthy volunteers were studied. Cough was assessed using a questionnaire and a 3 day diary, and volitional cough quantified by peak cough flow and sound intensity. Other clinical symptoms, smoking habit, affective state, oral secretions, bulbar signs, and quantitative assessments of swallowing and respiratory function were documented. Results Patients with MND coughed and choked significantly more often and to a greater degree than the healthy volunteers (26 of 37 patients with MND and 2 of 23 volunteers, p<0.001). Female sex, older age, abnormal speech, reduced swallowing capacity, and low forced vital capacity (FVC)% predicted were each significantly associated with excessive coughing and choking episodes in patients with MND. Smokers had significantly more severe and prolonged episodes of coughing and choking than non-smokers (p<0.05). Patients with upper motor neuron bulbar signs had a greater tendency to severe and prolonged episodes of coughing and choking than those without (p<0.05). Chest infections were reported only rarely among the patients who coughed and choked. ConclusionsCoughing and choking episodes are common in patients with MND but infrequently associated with overt chest infection. Upper motor neuron bulbar signs may both promote factors (for instance, dysphagia) which trigger cough and reduce volitional capacity to suppress it.

Menthol is widely used in candy, chewing gum, toothpastes, cigarettes and common cold medications. Menthol has been shown to stimulate cold receptors in the mouth and nose. The present paper puts forward the hypothesis that menthol, by its effects on oral and nasal cold receptors, may influence thirst, the drive to breathe, and arousal. The satisfying effects of menthol on thirst and breathing, together with an effect on arousal, may explain the popularity of menthol and account for the very large amount of menthol-containing products that are consumed each day.

Profiles white rapper Vanilla Ice, 22, (born Robby Van Winkle in Miami Florida). Huge success of his debut album `To the Extreme'; Hit single `Ice Ice Baby'; Fabrications in his official biography; Discovery by Dallas club owner Tommy Quon, now Ice's manager; Comments by SBK Records executives. INSET: Two more reasons Vanilla Ice is just like Elvis..

Antihistamines are widely used in common cold medications, although the role of histamine in the development of common cold symptoms is unclear and the use of antihistamines for the treatment of common cold is controversial. It is clear that antihistamines do not offer a cure for common cold but they may alleviate symptoms of sneezing and runny nose. The present study was designed to investigate the efficacy of an antihistamine, doxylamine, on the symptoms of runny nose and sneezing associated with common cold.We conducted a randomized double-blind study in cold sufferers. One thousand and one volunteers with cold symptoms were screened in four centres (UK, Denmark, Belgium, Germany) and 688 satisfied the entry criteria of the study. The main reasons for excluding subjects were a low nasal secretion weight (secretion weight < 0.2 g, 72%) and a low subjective rhinorrhoea score (24%). Volunteers were randomized to receive either doxylamine succinate 7.5 mg by mouth four times a day up to nine doses (n = 345) or placebo (n = 343). The principal measurements were prospectively defined as runny nose and sneezing symptom scores. Data were analysed on an intention-to-treat basis, using Cochran-Mantel-Haenszel statistics controlling for baseline symptom scores.A between-group comparison showed that doxylamine-treated volunteers benefited from a significantly greater reduction in runny nose scores (P< 0.01) and sneezing scores (P< 0.001), than those volunteers in the placebo group. Doxylamine therapy was well tolerated; the incidence of unexpected side-effects was comparable with placebo. Of the expected side-effects, 13.3% of doxylamine-treated patients reported drowsiness. The incidence of sedative effects was lower than has been reported for other commonly used first-generation antihistamines.

Menthol and related cooling compounds such as ‘coolant agent 10’, are widely used in products ranging from common cold medications to toothpastes, confectionery, cosmetics and pesticides. The review brings together a range of information on production and chemistry of menthol, and its metabolism, mechanism of action, structure-activity relationships, pharmacology and toxicology. In particular, the coolant action and carminative actions of menthol are discussed in terms of actions on calcium conductance in sensory nerves and smooth muscle. The actions of menthol on the nose, respiratory reflexes, oral cavity, skin and gastrointestinal tract are reviewed.

The relative abilities of acoustic rhinometry, rhinomanometry, and subjective sensation of nasal patency, as recorded using a Visual Analogue Scale (VAS), were compared in a group of 51 healthy volunteers. All three methods were able to detect a change following the application of a nasal decongestant. A 27.5% change in minimum cross sectional area, a 13.29% change in nasal resistance, and a 30.7% change in the sensation of nasal patency was observed. No correlation was demonstrated between either acoustic rhinometry or rhinomanometry and subjective sensation, and only a weak correlation was found between acoustic rhinometry and rhinomanometry.

The internal surface of the nasal cavity is geometrically complicated and does not lend itself readily to direct measurement. Simple geometric shapes were used as a model for changes in the nasal cavity. Following the introduction of specific changes to a particular system, the effect of these changes on the acoustic evaluation of the space was studied. Cylinders were chosen, as the wave path could be assumed to be perpendicular to the model surface. The acoustic rhinometer's accuracy was assessed in the presence of small and large variations in cross sectional area, in the presence of a series of consecutive area changes, and a gradual change in diameter. The effect of the introduction of acoustic leak was also modelled. The acoustic data acquired from these models was used to reconstruct the model in three dimensions. These reconstructions were compared to the original model. The acoustic rhinometer was found to resolve with reasonable accuracy the dimensions of small spaces; however, if regions of sudden large area changes were present in the space, the data beyond these regions was highly unreliable. Furthermore, the presence of acoustic leak in a system had a similar effect. Unless precautions are taken in the set-up and operation of the acoustic rhinometer, the potential for misinterpretation of data and the introduction of bias is very high.

The resistance to airflow of each nasal passage was measured using active, posterior, rhinomanometry. Application of pressure to the axilla for 15 min by means of a wooden crutch caused a reciprocal change in nasal resistance with an ipsilateral increase and a contralateral decrease in resistance. The results are discussed in terms of reflex changes in sympathetic tone to the nasal venous erectile tissue.

1. The effects of nasal stimulation using an air jet or balloon on the electromyographic (e.m.g.) activity of a nasal muscle, the levator labii superioris alaeque nasi component of the quadratus labii superioris muscle, were studied in the anaesthetized cat. 2. Respiratory related nasal e.m.g. activity was recorded and this normally consisted of two components, one coinciding with the onset of inspiratory airflow and a larger component which commenced at the onset of expiratory airflow and often persisted until the onset of the following inspiratory airflow. 3. An air jet (room air, 1‐8 l/min, temperature 24 degrees C) applied to the nasal vestibule by means of a small nozzle caused an increase in the amplitude of the ipsilateral spontaneous nasal e.m.g. activity. 4. The increase in nasal e.m.g. activity caused by the nasal air jet was unaffected by warming the airflow from 30 to 40 degrees C. 5. A sustained increase in nasal e.m.g. activity was caused by application of pressure to the walls of the nasal vestibule by means of a small balloon. 6. Section of the ethmoidal and infra‐orbital branches of the trigeminal nerve abolished the increase in nasal e.m.g. amplitude caused by nasal stimulation with the air jet, whilst section of the facial nerve abolished the spontaneous respiratory nasal e.m.g. activity. 7. The results indicate that there are sensory receptors in the nasal vestibule which respond to nasal positive pressure and cause a reflex increase in nasal e.m.g. activity.

The role of nasal heat exchange in the control of brain temperature has been studied in cats, pigs, ducks and rabbits during acute experiments under general anaesthesia. Nasal air flow at physiological rates caused hypothalamic temperature to fall at beween 0.2 and 0.5°C/min in cats, pigs and ducks, which all have arterial rete systems that can cool blood flowing to the brain, but not in rabbits, which lack an arterial rete. Bilateral stimulation of cervical sympathetic trunks reduced or abolished the brain cooling effect of nasal air flow in cats, pigs and ducks. After a period of airflow during which brain cooling was reduced by sympathetic stimulation, the end of stimulation was sometimes followed by marked and rapid brain cooling, indicating re-perfusion through ischaemic cooled tissues. Cervical sympathetic stimulation caused a reduction in resistance to nasal airflow in all species studied, by inducing vasoconstriction and shrinkage of the nasal mucosa. In species with well-developed arterial retia, the effect of cervical sympathetic stimulation in regulating nasal cooling of the brain is probably mediated by controlling blood flow through the nasal mucosa. Although this vascular control also occurs in rabbits, they cannot selectively cool the brain and sympathetic stimulation has no effect on rabbit brain temperature.

The effects of five minutes exposure to camphor, eucalypths or menthol vapour on nasal resistance to airflow and nasal sensation of airflow were compared with the effects of exercise on the nose. Inhalation of camphor, eucalyptus or menthol had no effect on nasal resistance to airflow but the majority of subjects reported a cold sensation in the nose with the sensation of improved airflow. Exercise caused a decrease in nasal resistance but did not induce any nasal sensation of cold or improved airflow. The results indicate that camphor, eucalyptus and menthol stimulate cold receptors in the nose. The clinical significance of nasal sensation of airflow is discussed.

Asymmetrical nasal vasomotor oscillations mediated via the cervical sympathetic nerve have been observed in the spontaneously breathing cat. The vasomotor activity persists after abolition of spontaneous respiration with a neuromuscular relaxant agent indicating that the vasomotor activity originates in the respiratory areas of the brain and is not due to any of the mechanical effects of respiration. The nasal vasomotor activity is abolished on hyperventilation indicating that it may be driven from a central respiratory oscillator. The vasomotor activity exhibits a reciprocal activity with oscillations in sympathetic activity alternating from one nasal passage to the other and this may be due to a direct relationship with a nasal cycle in the cat.

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 > 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.

1.Nasal vasomotor oscillations were studied in 23 anaesthetised cats. The oscillations occurred in all cats and showed both respiratory (vasoconstriction in inspiration) and non-respiratory rhythms. In all cases the oscillations were asymmetrical between the two sides of the nose, and the side with greater oscillations also had a higher level of nasal vasoconstriction.2.Oscillations shifted from one side to the other, both spontaneously and in response to stimulation of the brainstem reticular formation. Induced shifts were nearly always to the stimulated side, and preceded by ipsilateral vasoconstriction and contralateral vasodilation. This reciprocal pattern was shown in 19 out of 89 responsive sites, and is similar to changes shown spontaneously in the nasal cycle.3.Non-respiratory oscillations were seen at some time in most preparations and varied from frequency doubling to complete independence from respiration.4.The evidence presented indicated that nasal vasomotor oscillations are driven from sympathetic oscillators which may be independent of, or can be entrained by, central respiratory activity. The oscillators show reciprocal inhibition, and electrical stimulation over a poorly-defined area of the brainstem reticular formation can shift the balance of activity between them, though responses from any one site depend on the existing state of the oscillating system.

1. A study has been made in the anaesthetized cat of the stimulation parameters required to separate the vasodilator and vasoconstrictor responses evoked in the nose by stimulating the cut peripheral end of the Vidian nerve.

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, r 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.

Summary Vasomotor responses from the nasal mucosa and tongue, and contractions of the nictitating membrane, were recorded on stimulation of the cervical sympathetic or internal carotid nerves.

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, p0.81). The control stimulus group 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.

Middle ear preassure and nasal airway resistance were measured over 71/2 h 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 -140daPa. 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.

Codeine is generally accepted as the standard antitussive against which new antitussive medications are compared. This presents a problem because the support for codeine's antitussive activity comes from studies on cough in animals, and chronic and induced cough models in man, whereas antitussives are almost exclusively used for the treatment of cough associated with acute upper respiratory tract infection (URTI). The aims of this study were twofold. Firstly, to study the antitussive efficacy of codeine in cough associated with URTI and, secondly, to validate a sound meter as tool for quantifying cough.

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.

The resistance to air flow of each nasal passage in the anaesthetized pig was determined by pumping air through the nose and measuring pressure changes in nasal cannulae. A nasal cycle was observed in the majority of the pigs. Three types of change in nasal resistance were observed and their possible causes are discussed. Section of the right cervical sympathetic nerve abolished the cyclic changes in nasal resistance of both nasal passages. The method described may prove useful in studying the physiology of the nasal cycle.

The nasal resistance to airflow was determined in four subjects for periods of up to 7 hr. Cyclic changes in the resistance of each nasal passage were demonstrated in 13 of 24 experiments. After exercise on the cycle ergometer the total nasal resistance decreased and this change in nasal resistance was found to be directly related to the work rate. After oral rebreathing, the total nasal resistance decreased, and after hyperventilation the total nasal resistance increased. These changes in resistance are believed to be caused by changes in arterial pCO2 and mediated by the autonomic innervation of the nasal vasculature.

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. The sensation of throat irritation on nasal challenge with bradykinin may be due to stimulation of sensory nerves in the nasopharynx. This finding may explain why sore throat is often reported as an early symptom of common cold as bradykinin generated by nasal infection would be cleared towards the nasopharynx.

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< 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< 0.0001) with a correlation in the changes seen in both parameters (r 0.82, r2 0.66, p < 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.

Objective and subjective measurements of nasal airflow were made before and after inhalation of vanilla and a commercial mixture of aromatics used to treat nasal stuffiness. These substances had no effect on nasal resistance to airflow but caused significant changes in the subjective sensation of nasal airflow. The use of a visual numerical scale for the assessment of nasal sensation of airflow is discussed in terms of its significance as regards quantifying changes in nasal sensation of airflow before and after nasal surgery.

Abstract: The incidence of rhinitis is on the increase, especially in towns and cities with high levels of pollution from motor traffic and industry. There is a growing body of evidence which links this increased incidence of rhinitis to chronic nasal irritation from industrial pollution. Studies on the mechanisms of nasal inflammation and the nasal immune response are now providing insights into the etiology of rhinitis. This knowledge will help in the development of therapies aimed at alleviating the symptoms of rhinitis and controlling the development of rhinitis in susceptible individuals. This review discusses some of the factors that may explain the increased incidence of rhinitis and examines basic mechanisms involved in the nasal response to infection and allergy.

Nasal congestion associated with the common cold or allergy is associated with a decreased sensitivity of the sense of smell. This study was designed to detect any relationship between nasal resistance to airflow and the ability to detect odors presented to the nose. In particular we were interested to determine if the asymmetrical nasal resistance to airflow associated with the nasal cycle influenced nasal thresholds to menthol which is detected by trigeminal nerves and vanillin which is detected by olfactory nerves. Nasal resistance to airflow and the thresholds for L-menthol and vanillin were measured for each nasal passage in 17 normal volunteer subjects. Nasal resistance to airflow was asymmetrical due to the nasal cycle with a resistance on the high side of 0.94±0.15 Pa/cm3 s (mean ±S.E. n=17). and 0.48±0.04 Pa/cm3 s on the low side. The range of unilateral nasal resistances varied from 0.31-2.55 Pa/cm3 s. Despite these variations in nasal resistance to airflow no relationship was found between nasal resistance to airflow and thresholds for menthol or vanillin. Since threshold and nasal resistance are not related in normal subjects this may indicate that it is not the level of nasal congestion that affects the sense of smell in nasal infection and allergy, but some other factor related to the inflammatory response of the nasal mucosa.

A method for accurately predicting the average fundamental frequency of the larynx from an external measurement of laryngeal size has been developed. In 21 human cadaveric dissections we have demonstrated that the external height of the larynx (measured from the lower border of the cricoid cartilage to the upper border of the thyroid notch) was significantly correlated to the length of the membranous vocal fold (r=0.94, p<0.001). This same external measure of laryngeal size in 115 healthy volunteers was found to be related to their voice fundamental frequency. Significant differences were found between males and females with respect to both laryngeal size (p<0.001) and voice fundamental frequency (p<0.001). A strong correlation between the external laryngeal measurement and speaking fundamental frequency was found with an overall correlation coefficient for both sexes of 0.8 (p<0.001). Using this external measurement, it may be possible to accurately predict the fundamental frequency in males and females. It is proposed that such a measurement could be used to identify various laryngeal diseases and also serve as a basis for corrective treatment in various voice disorders.

It is now over 100 years since Kayser (Archiv Fur Laryngol Rhinol 1895; 3; 101-120) first reported in the scientific literature that the human nasal passages exhibit spontaneous changes in unilateral nasal airway resistance, yet our understanding of this unusual phenomenon is still very confused. Spontaneous, reciprocal changes in unilateral nasal resistance are often referred to as a "nasal cycle" and although this term is now commonly used to describe spontaneous changes in nasal resistance in man and animals, there is little evidence for any true periodicity. A major problem in increasing our knowledge and understanding of the so-called "nasal cycle" is that most studies have relied on simple descriptions of the changes in nasal resistance and have not developed any numerical parameters to quantify the changes in resistance over time. This lack of definition of what actually constitutes a nasal cycle has meant that the literature of the present day generally accepts the views put forward by Heetderks (Am J Med Sci 1927; 174: 231-244) and Stoksted (Acta Otolaryngol (Stockh) 1953; Suppl 109: 159-175) that around 80% of the healthy population exhibit a regular cycle. In order to define the characteristics of the spontaneous changes in nasal airway resistance we have used numerical measures of reciprocity and also developed a measurement of the division of airflow between the nasal passages over time. With these two parameters it is possible to describe the nature of the spontaneous changes in airflow in numerical terms and to define what exactly constitutes a nasal cycle. Fifty-two volunteers underwent hourly measurement of unilateral nasal airflow for 8 h. For each volunteer, two values were derived from the graph of unilateral nasal airflows against time: the correlation coefficient between unilateral airflows (r) and the airflow distribution ratio between the two nasal airways (ADR). The spread of different types of airflow pattern (nasal cycle) throughout the population was illustrated by plotting r against ADR for each subject. A nasal cycle was defined as having an r value between -0.6 and -1.0, and an ADR value between 0.7 and 1.0. Only 21% (11 of the 52 volunteers) exhibited airflow patterns that could be defined as a nasal cycle in these terms. This finding contradicts the generally accepted, but undefined, view that around 80% of the population exhibit a regular nasal cycle. The numerical definition of a nasal cycle in terms of both reciprocity and airflow distribution, as described in this paper may help to clarify our understanding of this interesting phenomenon and allow rhinologists to describe the spontaneous changes in nasal airflow in more exact terms than have been used previously in the literature.

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 analyser 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' (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.

Electrical stimulation of areas of the hypothalamus and mesencephalon in the anaesthetized cat induced bilateral nasal vasoconstriction, retraction of the nictitating membranes, and a rise in arterial blood pressure. the areas of the brain from which marked nasal vasoconstriction could be induced were similar to those previously described as the defence area, and it is suggested that nasal vasoconstriction may be one component of an integrated defence reaction. Some separation of the various autonomic responses induced on electrical stimulation of the hypothalamus was achieved by variation in either electrode position, stimulation frequency, or pulse duration. the results provide evidence which indicates that the hypothalamus is involved in the regulation of the sympathetic innervation of the nasal mucosa. This finding may be of some significance in understanding the aetiology of psychosomatic nasal disorders in Man.

Nasal airflow is normally asymmetrical and subject to spontaneous reciprocal changes which are often referred to as the 'nasal cycle'. the nature of these spontaneous changes in nasal resistance is poorly understood and little information is available about how they are affected by nasal disease. in order to understand the changes in nasal resistance in health and disease it is important to record unilateral resistance rather than express results as total nasal resistance. Unilateral resistance is subject to continuous reciprocal changes and therefore new measurements were developed in this study in order to quantify the nasal resistance of each nasal passage.Twelve human subjects (age 19-38) with symptoms of acute respiratory tract infection (URTI) were recruited for the study which involved serial measurements of unilateral nasal airway resistance using the technique of posterior rhinomanometry over a period of six hours. Measurements were made on one day when subjects had symptoms of URTI and then repeated 6-8 weeks later when subjects were healthy. the results of this study show that all of the subjects exhibited spontaneous reciprocal changes in nasal airway resistance on both study days but that there was a significant increase in the amplitude of the changes in resistance when the subjects had symptoms of URTI with one nasal passage often becoming severely congested. in order to quantify the amplitude of the reciprocal changes in nasal resistance two new measures were used. the minimum and maximum nasal airway resistance recorded for each nasal passage during the six hour recording period (MIN NAR and MAX NAR). Mean MIN NAR with URTI was 0.4 Pa em's ± 0.07 which was not significantly different from mean MIN NAR in health which was 0.36 Pa cm3s ± 0.05 (p = 0.22, n = 20). the mean MAX NAR during URTI was 2.44 Pa cm3s ± 0.38 and this decreased significantly to 1.36 + 0.17 when recorded during healthy conditions (p=0.01, n = 20). the increased amplitude of spontaneous reciprocal changes in nasal airway resistance associated with symptoms of URTI is proposed to be due to an increased filling pressure to the nasal venous sinusoids associated with a nasal inflammatory response. A model is proposed to explain the role of the nasal sympathetic vasoconstrictor tone and nasal venous filling pressure in the control of nasal airway resistance and to help explain the periods of unilateral nasal obstruction often associated with allergic and infective rhinitis.

Prostaglandins of the E series have been shown to be more potent than adrenaline as nasal decongestants. We now present evidence that prostaglandins of the E series (PGE) can be synthesised and inactivated by the nasal mucosa of the pig. This study demonstrates that PGE may be formed by pieces of pig nasal mucosa in vitro and that PGE formation by the nasal mucosa is inhibited by indomethacin. The nasal mucosa was also shown to contain 15-hydroxy prostaglandin dehydrogenase activity and this enzyme is involved in the inactivation of PGE. The findings of this study may help towards a better understanding of the role of PGE in nasal physiology and nasal disease.

The effect of nasal anaesthesia upon the sensation of nasal airflow and activity of menthol was investigated in 25 subjects using a visual analogue scale. Nasal anaesthesia was shown to decrease the sensation of nasal airflow, and also decrease the action of menthol in enhancing the sensation of nasal airflow. These differences were shown to be highly significant p < 0.001. Physiological mechanisms responsible for conveying the subjective appreciation of a nasal airflow stimulus are discussed, and also the site and nature of the sensory nerve endings involved.

In a lecture delivered by Dr. T. Clifford Allbutt, regius professor of physics in Cambridge University, England, before the Johns Hopkins University in October, 1898, occur these words1 : "The study of origins, then, is not only the new method of modern criticism, of modern history, of modern anthropology, of our reading of the evolution of the universe itself from elements which even themselves are falling under the same analytic inquiry, but the study of origins is leading to a revolution in our conceptions of therapeutics, as all of these other studies : a revolution which as yet we have not fully understood."Never were truer or more profound words uttered than these. The revolution to which Prof. Allbutt refers is one so momentous that but few have scanned the horizon of modern therapeutics closely enough to duly appreciate its far-reaching consequences and importance.

1. In cats anaesthetised with 50 mg/kg chloralose, 102 extensor a motoneurones were examined from hindlimb extensor nuclei. 2. On stimulation of ipsilateral cutaneous and muscle afferent fibres, many types of intracellular responses were recorded. In general, there was a flexor reflex IPSP and then a “chloralose IPSP” at the time of the chloralose jerk discharge recorded from flexor nerves. This was usually followed by a 50–75 msec depolarisation and finally a late, prolonged hyperpolarisation. 3. The “chloralose IPSPs” were more sensitive to increases in stimulus frequency than flexor reflex IPSPs and were abolished after spinal cord section. 4. The late prolonged hyperpolarisation was unaltered by increased chloride ion concentration within the cell and was often associated with a reduction in spontaneous synaptic noise.

1. Ninety flexor a-motoneurones mainly belonging to the PBST nucleus were examined in 27 cats anaesthetised with 50 mg/kg chloralose. 2. A fairly uniform intracellular response pattern was recorded on stimulation of ipsilateral cutaneous and muscle afferent fibres. There was an early EPSP corresponding to the flexor reflex; a second EPSP (usually with spikes superimposed) was designated a “chloralose EPSP” as it was associated with the chloralose jerk discharge recorded from the peripheral nerve; finally a prolonged hyperpolarisation, frequently associated with a reduction in synaptic activity. 3. The “chloralose EPSP” was more susceptible to increases in stimulus frequency and small doses of barbiturate than the flexor reflex EPSP. 4. The prolonged hyperpolarisation was unaltered by increased intracellular chloride ion concentration, and was therefore unlikely to be an IPSP generated at the motoneurone soma. 5. On spinal cord section, the flexor reflex EPSP and a late and prolonged hyperpolarisation were still recorded. However, the “chloralose EPSP” and the chloralose jerk discharge recorded from the peripheral nerve were abolished.

1. A flow of watery nasal secretion can be induced in the anaesthetized cat either by electrical stimulation of the brain stem or by the simpler procedure of stimulating the cut peripheral end of the Vidian nerve. In both instances the rate of flow of secretion was dependent on the stimulation frequency. Because brain stem stimulation caused an increase in arterial blood pressure, nasal secretion was evoked in subsequent experiments by Vidian nerve stimulation.