The activity of essential oils against the human head louse, Pediculus humanus capitis, has been investigated in a number of reports. Numerous essential oils have been found to exhibit pediculicidal activity in vitro, with common oils such as Eucalyptus globulus, Origanum marjo-rana, Rosmarinus officinalis, and Elettaria cardamomum being comparable to, or more effective than d-phenothrin and pyrethrum (Yang et al., 2004). Melaleuca alternifolia and Lavandula angustifolia have also been found to be highly effective pediculicidal agents (Willimason et al., 2007).
Despite the availability of positive in vitro results, only one trial involving application to humans has been documented; a mixture of anise and ylang ylang essential oils in coconut extract (Paranix®) was applied once to five children. Viable lice were not found after 7 days (Scanni and Bonifazi, 2006).
Recurrent aphthous stomatitis (RAS), also known as canker sores, are the most common oral mucosal lesions and although the process is sometimes self-limiting, the ulcer activity is mostly continuous and some forms may last for 20 years. Predisposing agents include bacteria and fungi, stress, mouth trauma, certain medications, and food allergies. Two essential oils both endemic to Iran have been investigated for treatment of this condition: Zataria multiflora, a thyme-like plant containing thymol, carvacrol, and linalool as major components, and Satureja khuzistanica containing predominantly carvacrol.
In a double-blind, randomized study, 60 patients with RAS received either 30 mL of an oral mouthwash composed of 60 mg of Zataria multiflora essential oil in an aqueous-alcoholic solution or placebo thrice daily for 4 weeks. In the treatment group, 83% of patients responded well while 17% reported a deterioration of their condition. This was compared with 13% and 87% for the placebo group, respectively. A significant clinical improvement with regard to less pain and shorter duration of the condition was found in the essential oil group (Mansoori et al., 2002).
Satureja khuzistanica essential oil 0.2% v/v was prepared in a hydroalcoholic solution and used in double-blind, randomized trial with 60 RAS patients. Its activity was compared with a 25% hydroalcoholic extract of the same plant and a hydroalcoholic placebo. A cotton pad was impregnated with 5 drops of preparation and placed on the ulcers for 1 min (fasting for 30 min afterwards) four times a day. The results of the extract and the essential oil groups were similar, with a significantly lower time for both pain elimination and complete healing of the ulcers in comparison with the placebo (Amanlou et al., 2007). The reported antibacterial, analgesic, antioxidant, and anti-inflammatory activities of this essential oil (Abdollahi et al., 2003; Amanlou et al., 2004, 2005) were thought responsible for the result.
Given the volatile nature of essential oils, it should come as no surprise that their ability to directly reach the site of intended activity via inhalation therapy has led to their use in the treatment of a range of respiratory conditions. Moreover, a number of components are effective when taken internally, since they are bioactive at the level of bronchial secretions during their excretion. With the exception of one report, all of the research has used the individual components of either 1,8-cineole or menthol, or has employed them in combination with several other isolated essential oil components within commercial preparations.
Menthol-containing essential oils have been used in the therapy of respiratory conditions for many years and the individual component is present in a wide range of over-the-counter medications. Of the eight optical isomers of menthol, l-(-)-menthol is the most abundant in nature and imparts a cooling sensation to the skin and mucous membranes.
Menthol is known to react with a temperature-sensitive (8-28°C range) transient receptor potential channel, leading to an increase in intracellular calcium, depolarization and initiation of an action potential (Jordt et al., 2003). This channel, known as TRPM8, is expressed in distinct populations of afferent neurons; primarily thinly myelinated A8 cool fibers and to a lesser extent, unmyeli-nated C-fiber nociceptors (Thut et al., 2003). It is the interaction with the TRPM8 thermoreceptor that is responsible for the cooling effect of menthol when it is applied to the skin. This activity is not confined to the dermis, since the presence of TRPM8 has been demonstrated by animal experimentation in the squamous epithelium of the nasal vestibule (Clarke et al., 1992), the larynx (Sant'Ambrogio et al., 1991), and lung tissue (Wright et al., 1998). Thus the activation of cold receptors via inhaled menthol leads to a number of beneficial effects.
Despite being used as a component in cough remedies since the introduction of a "vaporub" in 1890, there are few human trials of menthol used alone as being effective. In a citric acid-induced cough model in healthy subjects, Packman and London (1980) found that menthol was effective, although 1,8-cineole was more efficacious. The use of an aromatic unction rather than direct inhalation may have affected the results, since the inhalation of menthol has been shown in animal models to be significantly more effective at cough frequency reduction (28% and 56% at 10 and 30 g/l, respectively) compared to 1,8-cineole (Laude et al., 1994).
A single-blind pseudorandomized crossover trial in 42 healthy children was used to compare the effect of an inhalation of either menthol or placebo on citric acid-induced cough. It was found that cough frequency was reduced in comparison with the baseline but not to that of the placebo (Kenia et al., 2008). However, the placebo chosen was eucalyptus oil, whose main component is 1,8-cineole and known to have similar antitussive properties to menthol.
Along with other ion channel modulators, menthol is recognized as a potential "novel therapy" for the treatment of chronic cough (Morice et al., 2004, p. 489). It is not clear whether the antitussive activity of menthol is due solely to its stimulation of airway cold receptors; it may also involve pulmonary C-fibers (a percentage of which also express TRPM8) or there may be a specific interaction with the neuronal cough reflex.
Menthol is often thought of as a decongestant, but this effect is a sensory illusion. Burrow et al. (1983) and Eccles et al. (1988) showed that there was no change in nasal resistance to airflow during inhalation of menthol, although the sensation of nasal airflow was enhanced. In the former experiment, 1,8-cineole and camphor were also shown to enhance the sensation of airflow, but to a lesser extent than menthol.
In a double-blind, randomized trial subjects suffering from the common cold were given lozenges containing 11 mg of menthol. Posterior rhinomanometry could detect no change in nasal resistance to airflow after 10 min; however, there were significant changes in the nasal sensation of airflow (Eccles et al., 1990).
A single-blind pseudorandomized crossover trial compared the effect of an inhalation of either menthol or placebo. The main outcome measures were nasal expiratory and inspiratory flows and volumes, as measured by a spirometer and the perception of nasal patency, assessed with a visual analogue scale. It was found that there was no effect of menthol on any of the spirometric measurements although there was a significant increase in the perception of nasal patency (Kenia et al., 2008).
Thus it has been demonstrated that menthol is not a nasal decongestant. However, it is useful in therapy since stimulation of the cold receptors causes a subjective sensation of nasal decongestion and so relieves the feeling of a blocked nose. In commercial preparations that include menthol, a true decongestant such as oxymetazoline hydrochloride is often present.
188.8.131.52 Inhibition of Respiratory Drive and Respiratory Comfort
When cold air was circulated through the nose in human breath-hold experiments, subjects were able to hold their breath longer (McBride and Whitelaw, 1981) and inhaling cold air was shown to inhibit normal breathing patterns (Burgess and Whitelaw, 1988). This indicated that cold receptors could be one source of monitoring inspiratory flow rate and volume. Several animal experiments demonstrated that the inhalation of cold air, warm air, plus menthol, or menthol alone (390 ng/mL) significantly enhanced ventilator inhibition (Orani et al., 1991; Sant'Ambrogio et al., 1992).
Sloan et al. (1993) conducted breath-hold experiments with 20 healthy volunteers. The ingestion of a lozenge containing 11 mg of menthol significantly increased the hold time, indicating a depression of the ventilatory drive. It was later postulated by Eccles (2000) that in addition to chemoreceptors detecting oxygen and carbon dioxide in the blood, cold receptors in the respiratory tract may also modulate the drive to breathe.
Eleven healthy subjects breathed through a device that had either an elastic load or a flow-resistive load. Sensations of respiratory discomfort were compared using a visual analogue scale before, during, and after inhalation of menthol. It was found that the discomfort associated with loaded breathing was significantly reduced and was more effective during flow-resistive loading than elastic loading. Inhalation of another fragrance had no effect and so the result was attributed to a direct stimulation of cold receptors by menthol, a reduction in respiratory drive being perhaps responsible (Nishino et al., 1997).
During an investigation of dyspnea, the effect of menthol inhalation on respiratory discomfort during loaded breathing was found to be inconsistent. Further tests found that the effect of menthol was most important during the first few minutes of inhalation and in the presence of high loads (Peiffer et al., 2001). The therapeutic application of menthol in the alleviation of dyspnea has yet to be described.
184.108.40.206 Bronchodilation and Airway Hyperresponsiveness
The spasmolytic activity of menthol on airway smooth muscle has been demonstrated in vitro (Taddei et al., 1988). To examine the bronchodilatory effects of menthol, a small trial was conducted on six patients with mild to moderate asthma. A poultice-containing menthol was applied daily for 4 weeks and it was found that bronchoconstriction was decreased and airway hyperresponsiveness improved (Chiyotani et al., 1994b).
A randomized, placebo-controlled trial examined the effects of menthol (10 mg nebulized twice daily for 4 weeks) on airway hyperresponsiveness in 23 patients with mild to moderate asthma. The diurnal variation in the peak expiratory flow rate (a value reflecting airway hyperexcitability) was decreased but the forced expiratory volume was not significantly altered. This indicated an improvement of airway hyperresponsiveness without affecting airflow limitation (Tamaoki et al., 1995). Later in vivo research examined the effect of menthol on airway resistance caused by capsaicin- and neurokinin-induced bronchoconstriction; there was a significant decrease in both cases by inhalation of menthol at 7.5 ^g/L air concentration. The in vitro effect of menthol on bronchial rings was also studied. It was concluded that menthol attenuated bronchoconstriction by a direct action on bronchial smooth muscle (Wright et al., 1997).
In cases of asthma, the beneficial effects of menthol seem to be mainly due to its bronchodilatory activity on smooth muscle; interaction with cold receptors and the respiratory drive may also play an important role.
Recent in vitro studies have shown that a subpopulation of airway vagal afferent nerves expresses TRPM8 receptors and that activation of these receptors by cold and menthol excite these airway autonomic nerves. Thus, activation of TRPM8 receptors may provoke an autonomic nerve reflex to increase airway resistance. It was postulated that this autonomic response could provoke menthol-or cold-induced exacerbation of asthma and other pulmonary disorders (Xing et al., 2008). Direct cold stimulation or inhalation of menthol can cause immediate airway constriction and asthma in some people; perhaps the TRPM8 receptor expression is upregulated in these subjects. The situation is far from clear.
The respiratory effects of menthol that have been demonstrated are as follows:
1. Antitussive at low concentration.
2. Increases the sensation of nasal airflow giving the impression of decongestion.
3. No physical decongestant activity.
4. Depresses ventilation and the respiratory drive at comparatively higher concentration.
5. Reduces respiratory discomfort and sensations of dyspnea.
A number of in vitro and animal experiments have demonstrated the bronchomucotropic activity of menthol (Boyd and Sheppard, 1969; Welsh et al., 1980; Chiyotani et al., 1994a), whereas there have been conflicting reports as to whether menthol is a mucociliary stimulant (Das et al., 1970) or is ciliotoxic (Su et al., 1993). Apart from the inclusion of relatively small quantities of menthol in commercial preparations that have known beneficial mucociliary effects, there are no documented human trials to support the presence of these activities.
This oxide has a number of biological activities that make it particularly useful in the treatment of the respiratory tract. 1,8-Cineole has been registered as a licensed medication in Germany for over 20 years and is available as enteric-coated capsules (Soledum®). It is therefore not surprising that the majority of the trials originate from this country and use oral dosing of 1,8-cineole instead of inhalation. Rather than discuss specific pathologies, the individual activities will be examined and their relevance (alone or in combination) in treatment regimes should become apparent.
The anti-infectious properties of essential oils high in 1,8-cineole content may warrant their inclusion into a treatment regime but other components are more effective in this regard. 1,8-Cineole is often considered to have marginal or no antibacterial activity (Kotan et al., 2007), although it is very effective at causing leakage of bacterial cell membranes (Carson et al., 2002). It may thus allow more active components to enter the bacteria by permeabilizing their membranes.
1,8-Cineole does possess noted antiviral properties compared to the common essential oil components of borneol, citral, geraniol, limonene, linalool, menthol, and thymol; only that of eugenol was greater (Bourne et al., 1999). However, in comparison with the potent thujone, the antiviral potential of 1,8-cineole was considered relatively low (Sivropoulou et al., 1997).
A placebo-controlled, double-blind, randomized parallel-group trial examined the long-term treatment of 246 chronic bronchitics during winter with myrtol standardized Gelomyrtol® forte. This established German preparation consists mainly of 15% a-pinene, 35% limonene, and 47% 1,8-cine-ole and was administered thrice daily in 300 mg capsules. It was found to reduce the requirement for antibiotics during acute exacerbations; 51.6% compared to 61.2% under placebo. Of those patients needing antibiotics, 62.5% in the test group required them for <7 days whereas 76.7% of patients in the placebo group needed antibiotics for more than 7 days. Moreover, 72% of patients remained without acute exacerbations in the test group compared to 53% in the placebo group (Meister et al., 1999).
Although emphasis was given to antibiotic reduction, a significant antimicrobial effect by the preparation is unlikely to have paid an important contribution. Indeed, Meister et al. refer to reduced health impairment due to sputum expectoration and cough, and note other beneficial properties of 1,8-cineole that will be discussed in Sections 220.127.116.11 through 18.104.22.168.
The antitussive effects of 1,8-cineole were first proven by Packman and London in 1980, who induced coughing in 32 healthy human subjects via the use of an aerosol spray containing citric acid. This single-blind crossover study examined the effect of a commercially available chest rub containing, among others, eucalyptus essential oil. The rub was applied to the chest in a 7.5 mg dose and massaged for 10-15 s after which the frequency of the induced coughing was noted. It was found that the chest rub produced a significant decrease in the induced cough counts and that eucalyptus oil was the most active component of the rub.
1,8-Cineole interacts with TRPM8, the cool-sensitive thermoreceptor that is primarily affected by menthol. In comparison with menthol, the effect of 1,8-cineole on TRPM8 (as measured by Ca2+ influx kinetics) is much slower and declines more rapidly (Behrendt et al., 2004). In a similar manner to menthol, the antitussive activity of 1,8-cineole may be due in part to its stimulation of airway cold receptors.
In vitro tests using guinea pig trachea determined that the essential oil of Eucalyptus tereticornis had a myorelaxant, dose-dependent effect (10-1000 mg/mL) on airway smooth muscle, reducing tracheal basal tone and K+ -induced contractions, as well as attenuating acetylcholine-induced contractions at higher concentrations (Coelho-de-Souza et al., 2005). This activity was found to be mainly due to 1,8-cineole, although the overall effect was thought due to a synergistic relationship between the oxide and a - and b -pinene. Similar results were obtained using the essential oil of Croton nepetaefolius, whose major component was also 1,8-cineole (Magalhaes et al., 2003).
A double-blind, randomized clinical trial over 7 days compared oral pure 1,8-cineole (3 x 200 mg/ day) to Ambroxol (3 x 30 mg/day) in 29 patients with chronic obstructive pulmonary disease (COPD). Vital capacity, airway resistance, and specific airway conductance improved significantly for both drugs, whereas the intrathoracic gas volume was reduced by 1,8-cineole but not by Ambroxol. All parameters of lung function, peak flow, and symptoms of dyspnea were improved by 1,8-cineole therapy, but were not statistically significant in comparison with Ambroxol due to the small number of patients. In addition to other properties, it was noted that the oxide seemed to have bronchodila-tory effects (Wittman et al., 1998).
Mucolytics break down or dissolve mucus and thus facilitate the easier removal of these secretions from the respiratory tract by the ciliated epithelium, a process known as mucociliary clearance. Some mucolytics also have a direct action on the mucociliary apparatus itself.
Administered via steam inhalation to rabbits, 1,8-cineole in concentrations that produced a barely detectable scent (1-9 mg/kg) augmented the volume output of respiratory tract fluid from 9.5% to 45.3% (Boyd and Sheppard, 1971), an effect that they described as "mucotropic." Interestingly, in the same experiment fenchone at 9 mg/kg increased the output by 186.2%, thus confirming the strong effects of some ketones in this regard. Also using rabbits, Zanker (1983) found that oxygenated mono-terpenoids reduced mucus deposition and partially recovered the activity of ciliated epithelium.
Because of these early animal experiments, the beneficial effects of 1,8-cineole on mucociliary clearance have been clearly demonstrated in a number of human trials. Dorow et al. (1987) examined the effects of a 7-day course of either Gelomyrtol forte (4 x 300 mg/day) or Ambroxol (3 x 30 mg/day) in 20 patients with chronic obstructive bronchitis. Improved mucociliary clearance was observed in both groups, although improvement in lung function was not detected.
Twelve patients with chronic obstructive bronchitis were given a 4-day treatment with 1,8-cineole (4 x 200 mg/day). By measuring the reduction in percentage radioactivity of an applied radioaerosol, significant improvements in mucociliary clearance were demonstrated at the 60 and 120 min after each administration (Dorow, 1989).
In a small double-blind study, the expectorant effect of Gelomyrtol forte (1 x 300 mg/day, 14 days) was examined in 20 patients with chronic obstructive bronchitis. The ability to expectorate, frequency of coughing attacks, and shortness of breath were all improved by the therapy, as was sputum volume and color. Both patients and physicians rated the effects of Gelomyrtol forte as better than the placebo, but due to the small group size statistically significant differences could not be demonstrated (Ulmer and Schott, 1991).
A randomized, double-blind, placebo-controlled trial was used to investigate the use of mucolytics to alleviate acute bronchitis (Mattys et al., 2000). They compared Gelomyrtol forte (4 x 300 mg, days 1-14), with Ambroxol (3 x 30 mg, days 1-3; 2 x 30 mg, days 4-14) and Cefuroxime (2 x 250 mg, days 1-6) in 676 patients. By monitoring cough frequency data, regression of the frequency of abnormal auscultation, hoarseness, headache, joint pain, and fatigue, it was shown that Gelomyrtol forte was very efficacious and comparable to the other active treatments. Overall, it scored slightly more than Ambroxol and Cefuroxime and was therefore considered to be a well-evidenced alternative to antibiotics for acute bronchitis.
Several studies have demonstrated a direct effect of 1,8-cineole on the ciliated epithelium itself. Kaspar et al. (1994) conducted a randomized, double-blind three-way crossover 4-day study of the effects of 1,8-cineole (3 x 200 mg/day) or Ambroxol (3 x 30 mg/day) on mucociliary clearance in 30 patients with COPD. Treatment with the oxide resulted in a statistically significant increase in the ciliary beat frequency of nasal cilia, a phenomenon that did not occur with the use of Ambroxol (an increase of 8.2% and 1.1%, respectively). A decrease of "saccharine-time" was clinically relevant and significant after 1,8-cineole therapy (241 s) but not after Ambroxol (48 s). Lung function parameters were significantly improved equally by both drugs.
After the ingestion of Gelomyrtol forte (3 x 1 capsule/day for 4 days) by four healthy persons and one person after sinus surgery, there was a strong increase in mucociliary transport velocity, as detected by movement of a radiolabeled component (Behrbohm et al., 1995).
In sinusitis, the ciliated beat frequency is reduced and 30% of ciliated cells convert to mucus-secreting goblet cells. The impaired mucociliary transport, excessive secretion of mucus, and edema block drainage sites leading to congestion, pain, and pressure.
To demonstrate the importance of drainage and ventilation of sinuses as a therapeutic concept, Federspil et al. (1997) conducted a double-blind, randomized, placebo-controlled trial using 331 patients with acute sinusitis. The secretolytic effects of Gelomyrtol forte (300 mg) over a 6-day period proved to be significantly better than the placebo.
Kehrl et al. (2004) used the known stimulatory effects of 1,8-cineole on ciliated epithelium and its mucolytic effect as a rationale for treating 152 acute rhinosinusitis patients in a randomized, doubleblind, placebo-controlled study. The treatment group received 3 x 200 mg 1,8-cineole daily for 7 days. There was a clinically relevant and significant improvement in frontal headache, headache on bending, pressure point sensitivity of the trigeminal nerve, nasal obstruction, and rhinological secretions in the test group, as compared to the control group. It was concluded that 1,8-cineole was a safe and effective treatment for acute nonpurulent rhinosinusitis before antibiotics are indicated.
The effects of 1,8-cineole on stimulated human monocyte mediator production were studied in vitro and compared with that of budesonide, a corticosteroid agent with anti-inflammatory and immuno-suppresive effects (Juergens et al., 1998a). At therapeutic levels, both substances demonstrated a similar inhibition of the inflammatory mediators leukotriene B4 (LTB4), PGE2, and interleukin-1b (IL-1P). This was the first evidence of a steroid-like inhibition of arachidonic acid metabolism and IL-1P production by 1,8-cineole.
Later that year, the same team (Juergens et al., 1998b) reported a dose-dependent and highly significant inhibition of tumor necrosis factor-a (TNF-a), IL-1P, thromboxane B2, and LTB4 production by 1,8-cineole from stimulated human monocytes in vitro.
A third experiment combined ex vivo and in vivo testing; 10 patients with bronchial asthma were given 3 x 200 mg of 1,8-cineole daily for 3 days. Lung function was measured before the first dose, at the end of the third dose and 4 days after discontinuation of the therapy. At the same time, blood samples were taken from which monocytes were collected and stimulated ex vivo for LTB4 and PGE2 production. Twelve healthy volunteers also underwent the treatment and their blood was taken for testing. It was found that by the end of the treatment and 4 days after, the production of LTB4 and PGE2 from the monocytes of both asthmatics and healthy individuals was significantly inhibited. Lung function parameters of asthmatic patients were significantly improved (Juergens et al., 1998c).
These three reports suggested a strong anti-inflammatory activity of 1,8-cineole via both the cyclooxygenase and 5-lipooxygenase pathways, and the possibility of a new, well-tolerated treatment of airway inflammation in obstructive airway disease.
Juergens et al. (2003) conducted a double-blind, placebo-controlled clinical trial involving 32 patients with steroid-dependent severe bronchial asthma. The subjects were randomly assigned to receive either a placebo or a 3 x 200 mg 1,8-cineole daily for 12 weeks. Oral glucocorticoster-oids were reduced by 2.5 mg increments every 3 weeks with the aim of establishing the gluco-corticosteroid-sparing capacity of 1,8-cineole. The majority of asthma patients receiving oral 1,8-cineole remained clinically stable despite a mean reduction of oral prednisolone dosage of 36%, equivalent to 3.8 mg/day. In the placebo group, where only four patients could tolerate a steroid decrease, the mean reduction was 7%, equivalent to 0.9 mg/day. Compared with the placebo group,
I,8-cineole recipients maintained their lung function four times longer despite receiving lower doses of prednisolone.
Increased mucus secretion often appears as an initial symptom in exacerbated COPD and asthma, where stimulated mediator cells migrate to the lungs to produce cytokines; of particular importance are TNF-a, IL-1b, IL-6, and IL-8 and those known to induce immunoglobulin E (IgE) antibody synthesis and maintain allergic eosinophilic inflammation (IL-4 and IL-5). Therefore, a study was conducted to investigate the role of 1,8-cineole in inhibiting cytokine production in stimulated human monocytes and lymphocytes in vitro (Juergens et al., 2004). It was shown that 1,8-cineole is a strong inhibitor of TNF-a and IL-1b in both cell types. At known therapeutic blood levels, it also had an inhibitory effect on the production of the chemotactic cytokines IL-8 and IL-5 and may possess additional antiallergic activity by blocking IL-4 production.
A clinically relevant anti-inflammatory activity of 1,8-cineole has thus been proven for therapeutic use in airway diseases.
An inhaler was used to apply 1,8-cineole (Soledum Balm) to 24 patients with asthma or chronic bronchitis in an 8-day-controlled trial. In all but one patient, an objective rise in expiratory peak flow values was demonstrated. The subjective experience of their illness was significantly improved for all subjects (Grimm, 1987).
In an open trial of 100 chronic bronchitics using both inhaled (4 x 200 mg) and oral (3 x 200 mg) 1,8-cineole over 7 days, the clinical parameters of forced vital capacity, forced expiratory volume, peak expiratory flow, and residual volume were all significantly improved when compared to initial values before treatment (Mahlo, 1990).
In a randomized, double-blind, placebo-controlled study of 51 patients with COPD, 1,8-cineole (3 x 200 mg/day) was given for 8 weeks. For the objective lung functions of "airway resistance" and "specific airway resistance," there was a clinically significant reduction of 21% and 26%, respectively. The improvement was attributed to a positive influence on disturbed breathing patterns, mucociliary clearance, and anti-inflammatory effects (Habich and Repges, 1994).
The majority of the in vivo trials involving 1,8-cineole report good, if not significant, changes in lung function parameters, whether the investigation concerns the common cold or COPD. This is not a convenient, accidental side effect of treatment but is a direct result of one or more of the factors already discussed that have direct effects on the pathophysiology of the airways. The ability to breathe more effectively and easily is an important consequence of the therapy that is sometimes minimized when dealing with the specific complexities of infection, inflammation, and so on. A compilation of human trials with 1,8-cineole is given in Table 11.3.
Summary of Human Trials Demonstrating the Beneficial Effects of 1,8-Cineole in Various Respiratory Conditions
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