Exploring the Role of Olfaction in CPAP Compliance: A Literature Review
By Bret F. Randall, J.D.
©2007
The numbers are shocking: One in four adults, 31% of all men and 21% of all women over 18, are “at high risk” for sleep apnea, based on analysis of the National Sleep Foundation’s 2005 Sleep in America survey (Hiestand, 2006). Another study estimates that one third of all people over 18 in primary care are “at high risk” for sleep apnea (Netzer, 2003). Thus, between 50 and 60 million Americans are at high risk for sleep apnea (based on the 2000 Census), a significant increase from previous estimates.
Continuous positive airway pressure (CPAP) therapy is the treatment of choice for sleep apnea; it’s simple, economical, and effective. Unfortunately, despite the serious risks posed by untreated sleep apnea and improvements to CPAP equipment (such as heated humidification), CPAP compliance rates remain extremely low: As many as half of patients discontinue CPAP use within the first week and up to 25% of the remaining patients may be expected to have discontinued therapy within three years (Engleman 2003; Kribbs, 1993). Patterns developed during the first few nights of CPAP therapy have been shown to be highly predictive of long-term compliance (Weaver, 1997).
With the advent of behavioral sleep medicine in the last 15 years, researchers are increasingly focusing on psychological variables associated with CPAP compliance. Depression, mood, and anxiety (Edinger, 1994; Lewis, 2004), as well as personal coping strategies (Stepanowsky, 2002a) have been shown to be factors that affect CPAP compliance. Of psychological variables, anxiety appears to be a significant issue, with feelings of claustrophobia being reported in 11 to 28 percent of patients (Lewis, 2004). A growing number of intervention programs currently under development focus on improving psychological variables, including equipment de-sensitization, intensive training, in-home follow-up care, telemedicine, and group training, education, and experience sharing (Stepnowsky, 2002b; Haynes, 2005; Likar, 1997). Studies from compliance programs that focus on improving psychological variables associated with CPAP use are showing success in improving compliance rates.
While an association between CPAP compliance and olfaction has not been suggested before, a growing number of studies shows that pleasant aromatics are effective in improving the very same kinds of psychological variables that affect CPAP compliance: mood, comfort, anxiety, depression, claustrophobia, etc. Existing research suggests that hedonically pleasant aromatics will reduce CPAP mask anxiety and increase acceptance and compliance. The use of scented anesthesia masks, particularly in pediatrics, is widespread to reduce anesthesia mask anxiety. Aromatics have been demonstrated to be effective in reducing patient anxiety and improving comfort associated with unpleasant medical procedures and pain perception and management. Pleasant aromatics also present an effective mode of CPAP equipment desensitization.
At the same time, research also suggests that chemosensory irritation may play a role in reducing CPAP compliance. Virtually all CPAP equipment emits volatile organic compounds (VOCs) such as vinyl chloride (the “new car” smell), styrene, and DEHP, all well-known chemosensory irritants. Because new CPAP equipment imparts the most intense plastic aromas during the first several days of use, irritation and anxiety caused by those smells would be expected to be most significant during the most critical first week of CPAP use for new patients. Pleasant aromatics may be effective to counteract the negative impacts of chemosensory irritation caused by VOCs in CPAP equipment.
Human Olfaction
Among the human senses, olfaction is unique for a number of reasons. Unlike other sensory neurons, olfactory receptor cells are in direct contact with the external environment, where olfactory cilia extend down into the mucous layer covering the olfactory epithelium, the odor-sensitive tissue region in the nose (Dalton, 2001). In addition, olfactory stimuli bypass the brain stem and are presented directly to the primary sensory cortical areas and limbic system: “Olfactory neurons have a single unbranched axon that projects directly to the brain without synapsing on intermediate neurons” (Dalton, 2001). The direct neurological connections between the olfactory system and the higher cortical regions of the brain, combined with the presence of as many as 10 million olfactory cells in humans, “may account, in part, for the olfactory system’s capacity to detect and respond to minute concentrations of odorants” (Dalton, 2001).
The perception of smell is dominated by a hedonic (pleasantness-unpleasantness) dimension and exposure to odorants produces robust approach and withdrawal responses (Zald, 1997). Olfaction is the only human sense possessing direct neurological connections between the amygdala and primary sensory cortex. “This anatomy suggests a high level of functional connectivity between the olfactory and limbic systems” (ibid.). Because the limbic system represents the emotional center of the brain, “olfactory perception robustly engages emotional processes.” (ibid.)
Physiological responses to odorants occur irrespective of whether or not the individual is consciously aware of the presence of the smell. For example, conditioning with unpleasant odors present below conscious detection limits induced negative mood (Kirk-Smith, 1983) and undetected odors have been shown to affect patterns of EEG activity (Lorig, 1990; Schwartz, 1994). Undetected smells also affect the sense of taste (Labbe, 2006). Functional MRI testing in a human test showed that sub-threshold odorants induced significant brain activation in all subjects (Sobel, 1999).
Aromatics Improve Sleep
The use of aromatics to bring about physiological and psychological effects is acknowledged worldwide in folk medicine (Tisserand, 1988) and in healthcare (Buckle, 2001). In folklore, pillows were filled with lavender flowers to help the restless fall sleep. While evidence of the effectiveness of lavender (and other fragrances) to improve sleep is predominantly anecdotal and is largely based upon case studies and small trials, an increasing body of scientific evidence now suggests that lavender essential oil may slow the activity of the central nervous system, improve sleep quality, promote relaxation, and lift mood.
Lavender’s general calming and sedative effects have been documented in several studies. Lavender demonstrated strong central nervous system depressant activity with sedative, anticonvulsive, anxiolytic, motor inhibitory and spasmolytic effects (Gyllenhaal, 2000). Caffiene-induced hyperactivity in mice was reduced to nearly normal locomotor activity upon lavender inhalation (Buchbauer, 1991). In humans, lavender has been shown to lower heart rate and blood pressure (Nagai, 2000; Romine, 1999) and to result in immediate physiological changes (including EEG) following exposure (Diego, 1998). Lavender has also been shown to slow reaction times (Klemm, 1992; Yagyu, 1994) and to reduce performance of cognitive tasks (Ludvigson, 1989). Lavender increases beta activity (Diego, 1998; Lorig, 1990), decreases alpha activity (Masago, 2000), and increases theta activity (Klemm, 1992). These findings are consistent with self-reported relaxing mood states induced by lavender exposure (Goel, 2005; Diego, 1998). Consistent with this data, early human case studies reported improved sleep and supported the use of lavender essential oil as a mild anxiolytic and sedative in elderly and demented patients (Hardy, 1991; Hardy, 1995; Henry, 1994; Hudson, 1996; Wolfe, 1996).
In 2005, a group of researchers set out to study the effect of lavender on sleep through a controlled human study, the first of its kind, by collecting standard polysomnographic sleep and self-rated sleepiness and mood data (Goel, 2005). The human study concludes that: “lavender serves as a mild sedative and has practical applications as a novel, nonphotic method for promoting deep sleep in young men and women and for producing gender-dependent sleep effects.” (Goel, 2005).
The proven ability of aromatics to induce physiological and psychological relaxation, as well as to improve sleep, suggests that aromatics should be incorporated into mainstream cognitive behavior therapy (CBT) for sleep disorders generally. It also suggests that aromatics would represent an effective modality to improve CPAP compliance.
Aromatics Significantly Reduce Anxiety and Claustrophobia in MRI Procedures
While no investigation to date has directly considered the effect of aromatics on CPAP compliance, a number of studies have demonstrated the effectiveness of pleasant aromatics on reducing psychological variables associated with various medical procedures.
In a study that is analogous to the suggested application, the use of aromatics was proven to be effective in reducing anxiety and distress in patients undergoing magnetic resonance imaging (MRI) during diagnostic work-up for cancer (Redd, 1995). During an MRI procedure, patients are slid into a 23-inch diameter tunnel in the center of a large MRI machine. Scans can last over one hour. In order to obtain a clear image the patient must remain still during the entire procedure.
Because of the severe restriction of movement and the confined spaces, some patients report feelings of claustrophobia and other forms of anxiety, particularly where the scan may confirm the presence of cancer. Up to 20% of patients are unable to complete the procedure due to anxiety, distress, and feelings of claustrophobia. This is similar to the report that up to 28% of new CPAP patients experience claustrophobia.
Based on previous work showing that fragrance reduces anxiety, the authors conducted a controlled study of patients undergoing MRI procedures. During the procedure, the control group was given humidified air through a nasal canula and the experimental group were given humidified air with bursts of heliotropin, a vanilla-like fragrance found to be highly relaxing and pleasant to most people.
Controlling for individuals who found heliotropin to be pleasant, administration of fragrance during the MRI procedure was shown to be associated with 63% less anxiety than administration of humidified air alone. The fragrance intervention was successful for the 70% of those patients who experienced heliotropin as pleasant. The authors hypothesize that cognitive distraction, combined with physiological relaxation in direct response to the physical properties of the fragrance were important mechanisms in the study.
Aromatics Improve Psychological Variables Associated with Medical Procedures and Pain Perception and Management
In a recent controlled study, ambient odors of orange and lavender were shown to be effective to reduce anxiety and improve mood in patients waiting for dental treatment (Lehrner, 2005). Similarly, in another study, aromatics were shown to have the potential to moderate various aspects of mood following an anxiety-provoking task (when individual hedonic preferences are controlled) (Burnett, 2004). In a study of full-term newborns, exposure to a familiar odor was shown to reduce agitation during routine heel stick procedures and to diminish distress after the procedure (Rattaz, 2005).
A number of studies have focused on the interaction between aromatics and pain. Studies have found that positively hedonic fragrances decreased pain response in mice, whereas negatively hedonic odors increased pain response (Jahangeer, 1997; Mellier, 1997). In a more recent study, the presence of peppermint odor resulted in an increase in the individual’s ability to withstand painful stimulus and well as promoted a decreased sensation of pain over time (Raudenbush, 2002). In another study, it was found that while odors significantly influence mood in both women and men, effects of odor on pain perception were experienced only by women, suggesting gender differences in the mechanisms involved in the emotional aspects of mood and pain perception (Marchand, 2002).
Chemosensory Irritation as a Psychological Variable in CPAP Compliance
CPAP equipment is made from various hard and soft plastic components, including polyvinyl chloride (PVC) and softening agents (phthalates or plasticizers), such as di-ethylhexylphthalate (DEHP), vinyl chloride, styrene, etc. PVC is the most widely used plastic in medical devices and DEHP is the most common plasticizer used in medical products, where it comprises 20-40% by weight of flexible plastic medical devices (as much as 80% in tubing).
Because plasticizers are not chemically bound to the polymer, they leach out during normal use. Among other things, the presence of heat and moisture are important factors in the rate of plasticizer leaching. In one study, endotracheal tubes used to provide CPAP treatment to premature newborns was shown to release 6% to 12% of its total mass, where doctors found that the tubing changed in color and flexibility after only a few hours use but also that plasticizer loss increased over time (Healthcare without Harm).
Wholly apart from potential health exposure risks, the odors associated with VOCs released from plastics used in medical devices are known to result in stress, anxiety, and discomfort from a chemosensory standpoint, even when present in extremely low concentrations, as discussed more fully above. The conscious odor threshold for styrene is 0.54 parts per million (ppm) and vinyl chloride can be detected at levels as low as 10 ppm. EPA’s Inhalation Reference Concentrations (RfC) represent an estimate of a continuous inhalation exposure concentration to people (including sensitive subgroups) that is likely to be without risk of deleterious effects during a lifetime (constant exposures). The RfC for styrene is 60 parts per billion (ppb) and 30 ppb for vinyl chloride. EPA’s Acute Exposure Guideline Level 1 (the level involving noticeable discomfort, with increasing severity of reversible effects) for vinyl chloride is 70 ppm (8 hour exposure) and for styrene is 20 ppm (4 hour exposure).
Chemosensory irritation to VOCs is also characterized by a latency effect, meaning that there may be considerable delay in the onset of irritation in contrast to odor perception, with irritation starting near the end of a typical working day (Baird, 1994; Wolkoff, 1991). Hence, in many CPAP patients, chemosensory irritations from VOCs may not begin until many hours into the night. The latency effect of chemosensory irritation may explain fractured sleep patterns experienced by CPAP patients.
Moreover, chemosensory irritation may play an important role in CPAP compliance due to gender differences in olfaction. While men tend to have a less sensitive sense of smell than women, men perceive greater olfactory intensity in emotional states than women, regardless of the valence of the olfactory stimuli (Chen, 2005). Because CPAP therapy creates emotional states in many people, especially new patients, men would be expected to perceive equipment-related VOC odors, as well as pleasant aromatics, more intensely than they would in a neutral state.
While the issue has not been directly studied, existing research in olfaction and plastic VOCs released by medical equipment supports the theory that VOCs released by new CPAP equipment is a significant psychological variable affecting CPAP compliance, particularly during the critical first two or three nights of therapy. It also stands to reason that plastic smells emitted by CPAP equipment exacerbate feelings of smothering, claustrophobia, stress, anxiety, and irritation. The use of pleasant aromatics in CPAP therapy should mitigate chemosensory irritations. In light of the fact that up to half of new CPAP patients give up on therapy during the first week, aromatics should be considered for new patients.
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