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.

https://onlinelibrary.wiley.com/doi/epdf/10.1111/j.2042-7158.1994.tb03871.x

Menthol and related cooling compounds.

Objective: To determine whether intranasal corticosteroids are superior to oral H 1 receptor antagonists (antihistamines) in the treatment of allergic rhinitis. Design: Meta-analysis of randomised controlled trials comparing intranasal corticosteroids with oral antihistamines. Setting: Randomised controlled trials conducted worldwide and published between 1966 and 1997. Subjects: 2267 subjects with allergic rhinitis in 16 randomised controlled trials. Main outcome measures: Nasal blockage, nasal discharge, sneezing, nasal itch, postnasal drip, nasal discomfort, total nasal symptoms, nasal resistance, and eye symptoms and global ratings. Outcomes measured on different scales were combined to determine pooled odds ratios (categorical outcomes) or standardised mean differences (continuous outcomes). Assessment of heterogeneity between studies, and subgroup analyses of eye symptoms, were undertaken. Results: Intranasal corticosteroids produced significantly greater relief than oral antihistamines of nasal blockage (standardised mean difference −0.63, 95% confidence interval −0.73 to −0.53), nasal discharge (−0.5, −0.6 to −0.4), sneezing (−0.49, −0.59 to −0.39), nasal itch (−0.38, −0.49 to −0.21), postnasal drip (−0.24, −0.42 to −0.06), and total nasal symptoms (−0.42, −0.53 to −0.32), and global ratings gave an odds ratio for deterioration of symptoms of 0.26 (0.08 to 0.8). There were no significant differences between treatments for nasal discomfort, nasal resistance, or eye symptoms. The effects on sneezing, total nasal symptoms, and eye symptoms were significantly heterogeneous between studies. Other combined outcomes were homogeneous between studies. Subgroup analysis of the outcome of eye symptoms suggested that the duration of assessment (averaged mean score over the study period versus mean score at end of study period) might have accounted for the heterogeneity. Conclusion: The results of this systematic review, together with data on safety and cost effectiveness, support the use of intranasal corticosteroids over oral antihistamines as first line treatment for allergic rhinitis.

https://www.bmj.com/content/bmj/317/7173/1624.full.pdf

Intranasal corticosteroids versus oral H1 receptor antagonists in allergic rhinitis: systematic review of randomised controlled trials

This article reviews the literature on the efficacy of treatment for voice disorders primarily using studies published in peer-reviewed journals. Voice disorders are defined, their frequency of occurrence across the life span is reported, and their impact on the lives of individuals with voice disorders is documented. The goal of voice treatment is to maximize vocal effectiveness given the existing disorder and to reduce the handicapping effect of the voice problem. Voice treatment may be (a) the preferred treatment to resolve the voice disorder when medical (surgical or pharmacological) treatments are not indicated; (b) the initial treatment in cases where medical treatment appears indicated; it may obviate the need for medical treatment; (c) completed before and after surgical treatment to maximize long-term post-surgical voice; and (d) a preventative treatment to preserve vocal health. Experimental and clinical data are reviewed that support these roles applied to various disorder types: (a) vocal misuse, hyperfunction and muscular imbalance (frequently resulting in edema, vocal nodules, polyps or contact ulcers); (b) medical or physical conditions (e.g., laryngeal nerve trauma, Parkinson disease); and (c) psychogenic disorders (e.g., conversion reactions, personality disorders). Directions for future research are suggested which maximize clinical outcomes and scientific rigor to enhance knowledge on the efficacy of voice treatment.

Treatment efficacy: voice disorders

Background: There is no consensus about the value of objective measurements of nasal patency.



Objective:  To assess the correlation between the subjective sense of nasal patency and the outcomes found with rhinomanometry and acoustic rhinometry.



Type of review:  Structured literature search.



Search strategy and evaluation method:  Review of English-language articles in which correlations were sought between subjective nasal patency symptoms and objective scores as found with rhinomanometry [nasal airway resistance (NAR)] and acoustic rhinometry [minimal cross-sectional area (MCA)]. Correlations were related to unilateral or combined assessment of nasal passages and to symptomatic nasal obstruction or unobstructed nasal breathing.



Results:  Sixteen studies with a level of evidence II-a or II-b fit the inclusion criteria and were further analysed. Almost every possible combination of correlations or lack thereof in relation to the variables included was found. However, when obstructive symptoms were present, a correlation between the patency symptoms with nasal airway resistance and minimal crosssectional area was found more often than in the absence of symptoms. In cases of bilateral assessment a correlation was found almost as often as it was not between patency symptoms and total nasal airway resistance or combined minimal crosssectional areas, while in the limited amount of studies in which unilateral assessment was done a correlation was found each time between patency symptoms and nasal airway resistance.



Conclusions:  The correlation between the outcomes found with rhinomanometry and acoustic rhinometry and an individual’s subjective sensation of nasal patency remains uncertain. Based on this review, it seems that the chance of a correlation is greater when each nasal passage is assessed individually and when obstructive symptoms are present. There still seems to be only a limited argument for the use of rhinomanometry or acoustic rhinometry in routine rhinologic practice or for quantifying surgical results.



Clin. Otolaryngol. 2009, 34, 518–525.

Correlation between subjective and objective evaluation of the nasal airway. A systematic review of the highest level of evidence

Background: Allergic rhinitis (AR) is a frequent disease affecting up to 20% of the population. AR causes a hypersensitivity reaction, which results in inflamed nasal mucosa and nasal congestion. Negative pressure generated during inspiration in the nasal airway secondary to nasal congestion may lead to nasal collapse, airway obstruction, and an increased number of sleep microarousals. Sleep disturbances and microarousals can detrimentally affect daytime energy levels, mood, and daytime function. It is unknown whether treatment directed to reduce congestion may reduce these microarousals, sleep problems, and, consequently, associated daytime fatigue. Objective: We sought to determine whether reducing nasal congestion with nasal steroids will reduce sleep complaints and daytime sleepiness. Method: We enrolled 20 subjects in a double-blind, placebo-controlled study using Balaam's Design. Patients were treated with topical nasal corticosteroids or placebo. Subjective data were collected by use of a daily diary, which focused on nasal symptoms, sleep, and daytime sleepiness. Results: The results demonstrated that nasal congestion and subjective sleep improved significantly in the topical corticosteroid–treated subjects but not in the placebo group. Sleepiness improved, but not significantly ( p  = 0.08). Conclusion: Often, people with perennial allergies may attribute their daytime fatigue to causes such as the side effects of medications, when in fact, the fatigue may be a result of nasal congestion and associated sleep fragmentation. Decreasing nasal congestion with nasal steroids may improve sleep, daytime fatigue, and the quality of life of patients with AR. (J Allergy Clin Immunol 1998;101:633-7.)

https://www.jacionline.org/article/S0091-6749%2898%2970171-X/pdf

Nasal congestion secondary to allergic rhinitis as a cause of sleep disturbance and daytime fatigue and the response to topical nasal corticosteroids

Fifteen subjects underwent nasal pressure gradient studies to determine the resistance profile of the nose. Seventy-nine per cent of nasal resistance to airflow occurred in the segment 0 cm.-2.8 cm. from the posterior margin of the anterior nares. The greater part of this resistance (43 per cent) occurred in the segment 1.5 cm.-2.8 cm. within the nose, and this area approximated to the site of the pyriform aperture. Eighteen patients underwent a trial of radical trimming of the inferior turbinates (12 patients) versus anterior trimming of the inferior turbinates (6 patients). Both operations produced a similar fall in nasal resistance to airflow, confirming that the region of the pyriform aperture was the site of maximum nasal resistance. Whereas the radical operation significantly reduced the sensation of nasal obstruction, the anterior operation did not. The results of the study are discussed with reference to previous work on the subject.

The nasal valve: a physiological and clinical study.

The effect of local anaesthesia of the nasal vestibule on nasal sensation of airflow and nasal resistance was assessed in 15 subjects. A single blind parallel group trial was undertaken in 30 subjects, with lignocaine as the active drug, and normal saline as the placebo. Fifteen subjects were included in each group. Both agents were infiltrated bilaterally into the floor of the nasal vestibule on each side via the sublabial route. Local anaesthesia of the nasal vestibule by infiltrating lignocaine produced a sensation of nasal obstruction in 9 out of 15 subjects (P less than 0.02). The infiltration of normal saline had no such effect. The difference between the effect of the 2 agents on nasal airflow sensation was significant (P less than 0.05). Neither injection had any significant effect on nasal resistance to airflow as assessed by active anterior rhinomanometry.

The effect of local anaesthesia of the nasal vestibule on nasal sensation of airflow and nasal resistance

A method of rhinomanometry is described for use in clinical research work. The statistical distribution of nasal resistance values is studied in a sample of 59 normal individuals. The variation of nasal resistance within two individuals is studied over a period of 7 hours. The choice of appropriate statistical tests to be used when comparing nasal resistance values is discussed. The reproducibility of nasal resistance measurements is assessed in 47 normal individuals. The results were used to define a normal range of values for total nasal resistance to airflow.

https://www.cambridge.org/core/services/aop-cambridge-core/content/view/S0022215100102762

Nasal resistance to airflow (its measurement, reproducibility and normal parameters).

The distribution of thermoreceptors within the nasal vestibule (that part of the nasal cavities lined with skin) and nasal cavum (that part of the nasal cavities lined with respiratory epithelium) was studied in 20 subjects. The distribution was compared with that of the malar skin adjacent to the nose. No thermoreceptors were located in the nasal cavum but the nasal vestibule contained a dense distribution of cold receptors (3.5 receptors per cm2) and warm receptors (3.2 receptors per cm2). The corresponding density of receptors in the malar skin was 2.7 receptors per cm2 and 2.6 receptors per cm2. The difference in distribution density between the nasal vestibule and the malar skin was significant (P less than 0.05). The implications of these findings are discussed.

The distribution of thermoreceptors within the nasal cavity.

In 1963, Brodnitz conducted a study which assessed the vocal recovery incidences for patients with voice problems, which included a group of patients with vocal cord nodules (singers' nodules). Nagata et al., (1983), compared the long-term outcome in vocal nodule patients treated by surgery alone, with those treated by minimal conservative measures, and those not treated at all. However, there is no reported study which compares the long-term outcome of patients with vocal cord nodules treated surgically with those treated with a combination of surgery and speech therapy, and those treated only with speech therapy.

The outcome of different management patterns for vocal cord nodules.

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