Ventilation rates and health: multidisciplinary review of the scientific literature.

UNLABELLED: The scientific literature through 2005 on the effects of ventilation rates on health in indoor environments has been reviewed by a multidisciplinary group. The group judged 27 papers published in peer-reviewed scientific journals as providing sufficient information on both ventilation rates and health effects to inform the relationship. Consistency was found across multiple investigations and different epidemiologic designs for different populations. Multiple health endpoints show similar relationships with ventilation rate. There is biological plausibility for an association of health outcomes with ventilation rates, although the literature does not provide clear evidence on particular agent(s) for the effects. Higher ventilation rates in offices, up to about 25 l/s per person, are associated with reduced prevalence of sick building syndrome (SBS) symptoms. The limited available data suggest that inflammation, respiratory infections, asthma symptoms and short-term sick leave increase with lower ventilation rates. Home ventilation rates above 0.5 air changes per hour (h(-1)) have been associated with a reduced risk of allergic manifestations among children in a Nordic climate. The need remains for more studies of the relationship between ventilation rates and health, especially in diverse climates, in locations with polluted outdoor air and in buildings other than offices. PRACTICAL IMPLICATIONS: Ventilation with outdoor air plays an important role influencing human exposures to indoor pollutants. This review and assessment indicates that increasing ventilation rates above currently adopted standards and guidelines should result in reduced prevalence of negative health outcomes. Building operators and designers should avoid low ventilation rates unless alternative effective measures, such as source control or air cleaning, are employed to limit indoor pollutant levels.

Differential sensitivity for smell: "noise" at the nose.

The ability of subjects to resolve differences in concentration of chemicals in the vapor phase by smell rivaled the optimum performance of chromatographs. In some instances, subjects resolved a difference in concentration of only 5 percent. The reported inability of olfaction to register fine differences in intensity seems to be largely a result of fluctuations in the stimulus.

To know with the nose: keys to odor identification.

Successful odor identification depends on (i) commonly encountered substances, (ii) a long-standing connection between an odor and its name, and (iii) aid in recalling the name. The absence of any one ingredient impairs performance dramatically, but the presence of all three permits ready identification of scores of substances, with performance seemingly limited only by the inherent confusability of the stimuli.

Cutoff in detection of eye irritation from vapors of homologous carboxylic acids and aliphatic aldehydes.

Using neat vapors of selected homologous aldehydes (decanal, undecanal, dodecanal) and carboxylic acids (pentanoic, hexanoic, heptanoic, octanoic, nonanoic), we explored the point where a certain homolog (and all larger ones) becomes undetectable by eye irritation (i.e. by ocular chemesthesis). This phenomenon has been observed in other homologous series that also reach a break-point, or cutoff, in chemesthetic detection. Participants (11

Reduction of odor and nasal pungency associated with aging.

Aging can seriously blunt suprathreshold sensations mediated by the olfactory receptor system and by common chemical receptors. Despite large individual differences, on the average any given stimulus seemed only about half as intense to the elderly (20 subjects, 65-83 yrs) as to the young (20 subjects, 18-25 yrs). The nature of the loss was a constant percentage reduction of perceived magnitude at stimulus levels from weak to strong. The stimuli were iso-amyl butyrate (a nonirritating fruity odor) and CO2 (which is practically odorless but triggers common chemical sensations effectively). The method used was magnitude matching, by which subjects made numerical estimates of the perceived magnitude of various levels of the two chemical stimuli and of the loudness of low-pitched noises. The loudness estimates served to adjust each subject's chemical estimates to help compensate for individual idiosyncrasies in the use of numbers and potential biases associated with age. Common chemical and olfactory losses seem to be unrelated; aging can dull one sense and leave the other acute.

Olfactory functioning in temporal lobectomy patients.

Seventeen patients who received unilateral excision of the temporal lobe for intractable epilepsy were compared to 46 normal controls on a battery of tests of olfactory functioning. Tests included quality discrimination, immediate and delayed recognition memory, matching an odor to its visually or haptically presented source, and verbal identification of odors and the function of stimulus objects. In spite of clinically normal absolute sensitivity, the patients performed significantly worse than controls on all tests of olfactory functioning. There were no significant differences in performance between dominant and non-dominant lobectomy patients. Likely explanations for the uniformly impaired performance of patients include deficits in quality discrimination and minor lapses of attention.

Odor perception in temporal lobe epilepsy patients with and without temporal lobectomy.

The investigation employed monorhinic (single nostril) olfactory testing to decide whether patients with unilateral anterior temporal lobe resection (N = 16) and patients with unoperated temporal lobe epilepsy (N = 18) have impaired ability to detect, remember, and identify odors. A shape memory task accompanied the odor memory task for comparison. The lobectomy patients showed a minor bilateral depression of absolute sensitivity but still fell within the clinically normal range. The lobectomy patients showed impairment of odor recognition memory but strictly via the nostril ipsilateral to the resected lobe. A similar ipsilateral-contralateral asymmetry characterized the performance of these patients in odor identification. In that case, however, performance via the contralateral nostril showed some impairment too. Nonsurgery patients also exhibited some impairment in odor identification, but bilaterally. Finally, both groups of patients fell somewhat below normals in recognition memory for amorphous shapes. The various results implied that temporal lobe epilepsy alone takes some toll on olfactory information processing and that temporal lobe resection exacerbates the problem, but only on the side of surgery.

Human breathing and eye blink rate responses to airborne chemicals.

Increased levels of air pollution have been linked with morbidity and mortality, but mechanisms linking physiologic responses to quality of life and productivity issues remain largely unknown. Individuals often report irritation of the nose and/or eyes upon exposures to environmental contaminants. Evaluation of these self-reports would be greatly aided by the development of valid physiological markers. Chamber studies (unencumbered exposures) of nonsmoker responses to environmental tobacco smoke offer two candidate end points: (a) Tidal volume increases and breathing frequency declines with stimuli that elicit only moderate irritation. (b) Eye blink rate increases only with a concentration sufficiently high to cause progressive worsening of eye irritation with prolonged exposure. Experiments with very brief nasal-only presentations also suggest the value of breathing changes as sensitive markers of irritation: (a) Tidal volume is inversely related to perceived nasal irritation (NI) intensity in both normal and anosmic (lacking olfactory input) individuals, although normals exhibit greater NI sensitivity. (b) Inhalation duration, in both groups, declines only with trigeminal activation sufficient to cause readily perceptible NI in anosmics. Changes in eye blink rate and breathing may be useful in the investigation of irritation and other effects of air pollution, and could be quite useful in investigations of mixtures of volatile organic compounds.

Uniformity of olfactory loss in aging.

Most studies of how human olfaction changes with age have compared young and old. Essentially all such studies imply that aging takes a toll. The elderly have higher thresholds, perceive suprathreshold odors as being weaker, discriminate quality less well, recognize and identify common odors less well, and remember episodic presentations of odors poorly. To a first approximation, it appears that all odor qualities and functions undergo a general blunting. The few studies of persons between the young and the elderly suggest that the process of deterioration sets in early and progresses gradually. Such gradual deterioration would presumably allow the easiest accommodation to any loss and may account for why many elderly people seem oblivious to it. In some respects, ignorance may be bliss. For example, the diminished flavor of food may go unnoticed. In other respects, the loss of olfactory information may pose some nutritional and safety risks of which the elderly and perhaps even the middle-aged should be apprised. Longitudinal studies would seem to offer the only chance to decide the rate and magnitude of individual losses in olfaction. Such studies might also offer enlightenment regarding ways to forestall loss.

Sensory irritation. Relation to indoor air pollution.

All mucosae of the body possess chemical sensitivity provided by the CCS. Airborne chemicals can stimulate the CCS through the ocular, nasal, and respiratory mucosae, evoking different pungent sensations, for example, stinging, irritation, burning, piquancy, prickling, freshness, and tingling. Pungent sensations elicited in the nose differ from odor sensations in various characteristics. They are achieved at considerably higher concentrations than those necessary to elicit odor, but they increase with the concentration of the stimulus in a steeper fashion than odor. Pungent sensations from mixtures of compounds show a higher degree of addition--relative to the pungency of the individual components--than that of odor sensations. Pungency is more resistant to adaptation than odor, and, unlike it, displays considerable temporal integration with continuous stimulation. Measurement of a reflex, transitory apnea produced upon inhalation of pungent chemicals holds promise as an objective indicator of the functional status of the CCS. Results from the measurement of this reflex have agreed quantitatively with sensory data in a number of studies, and have shown higher common chemical sensitivity in nonsmokers (compared to smokers), in females (compared to males), and in young adults (compared to the elderly). Research issues mentioned here include the following: 1. We can rarely validate the symptoms putatively caused by indoor air pollution objectively. Without such means, we will always have the potential problem of overreporting and embellishment. Although one person may seem more sensitive than another, the difference may lie in a greater proclivity to complain. 2. Studies of anosmic persons offer a simple means to understand the functional characteristics of the nasal CCS. Studies of chemical series in such subjects should eventually allow construction of quantitative structure-activity models for human pungency perception. The human data can be compared with relevant animal data when possible. 3. The rules of additivity of pungency in mixtures need explication. Regarding the possible role of VOCs in the creation of irritation, we need to ask whether subthreshold levels add up or even amplify each other to produce noticeable irritation. Do repetitive or continuous exposures to subthreshold concentrations increase sensitivity to those substances, so that they evoke pungency when they otherwise would not? Do the various mucose--ocular, nasal, throat--differ in their sensitivity? 4. Modulation of CCS sensitivity by long-term and short-term inhalation of various agents (for example, environmental tobacco smoke) would seem a suitable topic for further research.

Sensory properties of selected terpenes. Thresholds for odor, nasal pungency, nasal localization, and eye irritation.

We tested four normosmics and four anosmics in detection thresholds for six terpenes commonly found indoors: cumene, p-cymene, delta-3-carene, linalool, 1,8-cineole and geraniol. Normosmics provided odor thresholds and anosmics provided nasal pungency thresholds. All subjects provided nasal localization (i.e., right/left nostril) and eye irritation thresholds. Each type of threshold was measured eight times per subject-stimulus combination. Stimuli were presented from squeeze bottles in a two-alternative forced-choice procedure via an ascending method of limits. Odor thresholds ranged between 0.1 and 1.0 parts per million (ppm, by volume). Nasal pungency thresholds lay about three orders of magnitude above odor thresholds. Nasal localization and eye irritation thresholds did not differ between normosmics and anosmics, and fell close to nasal pungency thresholds. Olfactory thresholds could be obtained for all stimuli in all repetitions using the criterion of five correct choices in a row. Trigeminal thresholds (i.e., pungency, localization and eye irritation) could be obtained on all repetitions only for some terpenes using that same criterion. Carene and cineol produced nasal pungency and eye irritation on all repetitions. None of the terpenes could be localized on all repetitions, but cineol was localized a higher percentage of instances than were the other stimuli. At the other extreme, geraniol failed to evoke any of the three trigeminal responses in most instances. Overall, the results indicate that the three trigeminal thresholds produce a uniform view of the potency of these terpenes, with nasal pungency and eye irritation being slightly more sensitive than nasal localization. Furthermore, application of a previously derived linear solvation energy relationship to the results reinforced the view that physicochemical properties can predict the chemesthetic impact of volatile organic compounds.

Draize eye scores and eye irritation thresholds in man can be combined into one QSAR.

Draize eye scores (DES) of 37 pure organic liquids have been converted into scores for the corresponding vapors, DES/P0, where P0 is the liquid vapor pressure in atmospheres at 298 K. It is shown that there is a constant difference of 6.7 between values of log(DES/P0) and log (1/EIT), where EIT is the eye irritation threshold in parts per million (ppm, by volume) of eight vapors for human subjects. The 37 log(DES/P0) values can be combined with log(1/EIT) values for 17 vapors into one quantitative structure-activity relationship (QSAR) for sensory potency (SP) using our general solvation equation, [formula: see text] where R2 is an excess molar refraction, pi 2H is the compound polarizability/dipolarity, sigma alpha 2H and sigma beta 2H are the compound hydrogen-bond acidity and basicity, and L16 is the gas-hexadecane partition coefficient at 298 K. n is the number of data points, r the correlation coefficient, SD the standard deviation, and F the F-statistic. LogSP is then either [log(DES/P0) - 0.66] or log (1/EIT), confirming the result for the eight common compounds. It is suggested that the equation can be used to predict eye irritancy of organic vapors and pure liquids. It is further suggested that for the compounds in the data set, the main process in eye irritation is transfer of the compound from the vapor or pure liquid to a biological phase, and a number of chemical properties of the biological phase have been mapped out through the equation. These properties are consistent with corresponding properties for a number of organic liquid phases.

Ocular and nasal trigeminal detection of butyl acetate and toluene presented singly and in mixtures.

To probe into the rules of trigeminal chemosensory agonism in a binary mixture of chemicals we measured, first, the detectability (i.e., psychometric) function for eye irritation and for nasal pungency of butyl acetate and toluene, singly. (To avoid olfactory biases, nasal pungency was measured in a group of anosmics, i.e., persons lacking a functional sense of smell.) Then, based on the detectability function obtained for the individual chemicals, we prepared mixtures where the 2 components varied in their relative proportions but, if a simple rule of complete sensory agonism (in the sense of dose-additivity) were to hold, the mixtures should be as detectable as the reference concentration of each of the single chemicals. For both trigeminal endpoints (i.e., eye irritation and nasal pungency), the results showed that stimuli of relatively low detectability did show complete sensory agonism, whereas stimuli of relatively high detectability fell short of complete sensory agonism when compared with the detectability of the single substances. Further testing of additional binary and higher order mixtures will confirm whether or not a structure-activity model of trigeminal chemosensory impact of single chemicals, based on selected physicochemical parameters of the stimuli, can also be applied to chemical mixtures.

Remembered odors and mental mixtures: tapping reservoirs of olfactory knowledge.

Five experiments explored how (a) perceived and remembered odor intensities relate to concentration; (b) odor intensities integrate in perceptual, memorial, and mentally constructed mixtures; and (c) components vary in intensity in physical versus mental mixtures. Ss estimated the magnitude of unmixed stimuli presented physically (perceptual estimation) or represented symbolically (memorial estimation). Ss also judged mixtures and their components in combinations of perceptual and memorial presentation. Power functions with similar exponents described the relations between both perceived and remembered intensity and concentration. Perceptual, memorial, and mental mixtures all followed much the same interactive rule of integration. Correspondingly, the intensities of components varied similarly in mentally constructed and physical mixtures. The results imply intensive invariance across odor perception and odor memory.

Olfactory sensitivity: reliability, generality, and association with aging.

Thirty-two Ss between 22 and 59 years of age yielded detection thresholds for 4 odorants over 4 sessions. The thresholds decreased and reliability increased over the course of testing. High intercorrelations between odorants and the stability of an S's relative position within the threshold distributions showed that a general factor of sensitivity dominated the outcome. Age contributed strongly to intersubject variation. Even among these nonelderly individuals, it accounted for up to 2 orders of magnitude in threshold performance. Other important factors included superiority of the right nostril and a negative correlation between the mean and variance of threshold distributions. Scant attention to the correlation may have contributed to overestimation of the frequency and specificity of specific anosmia. A clinically relevant outcome was that measurement of threshold for diagnostic purposes can generally rely on just 1 odorant.

Perceptual and mental mixtures in odor and in taste: are there similarities and differences between experiments or between modalities? Reply to Schifferstein (1997)

D. Algom and W. S. Cain (1991b) found relative invariance in the pattern of judgments of perceptual and mental mixtures of banana and grass odors. Invariance held both for judgments of total intensity and for those of an individual constituent. For 2 tastes, H. N. J. Schifferstein (1997) found a pattern with both similarities to and differences from D. Algom and W. S. Cain's. A key difference lay in finding more symmetry of masking in mental mixtures than in perceptual mixtures. H. N. J. Schifferstein concluded from this alone that any similarity between the perceptual and mental arose from knowledge of "mixture suppression." The authors of this article do not refute the possibility; however, they reject the premise that a statistically reliable difference between the perceptual and the imaginal rules out imagery. The authors review relevant considerations and find no a priori reason to assume that what held for attributes in taste will hold for odors. An approach to resolve the issue is also suggested.

Aging and the perception of nasal irritation.

Three types of measurement were employed to assess the effects of aging on nasal irritation (common chemical sense). These were measurement of detection threshold of CO2 mixed with air, measurement of the threshold concentration of CO2 that causes a transient reflex apnea, and measurement of the suprathreshold perceived strength of five levels of CO2 by the method of magnitude matching. Ancillary measurements included nasal airflow resistance and magnitude matching of an odorant (1-butanol). Twenty elderly (67 to 93) and twenty young persons (19 to 31) served as subjects. The young and elderly gave no evidence of average difference in detection threshold. In contrast, the elderly group showed a strong elevation of the threshold of apnea and a marked weakening of perceived CO2 suprathreshold strength. CO2 and butanol approximated power functions of concentration level, functions for the elderly being depressed relative to those for the young. Although the elderly had on the average slightly higher nasal resistance than the young, the differences played at most a minor role in the perception of nasal stimuli.

Odor identification: the blind are better.

Twenty sighted and twenty blind adults, 19 to 66 years of age, participated in tests of olfactory sensitivity to n-butyl alcohol and of identification of 80 everyday odors. The blind had poorer absolute sensitivity, but outperformed the sighted at identification. Age proved an important factor in the comparison; more than half the variance in identification within each group was ascribable to an age-related decline.

Bilateral integration in the common chemical sense.

Human participants judged the pungency of various concentrations of carbon dioxide presented to one nostril, the other nostril, or both (dichorhinic stimulation). Perceived magnitude grew sharply with concentration over the range explored. The combinatorial rule of bilateral integration followed the Pythagorean theorem: the effective mass in a bilateral stimulus equalled the square root of the sum of squares of the mass entering each nostril. This simple rule implies a possible mutual inhibitory interaction between the two nostrils, but it also implies partial spatial summation of the sensory impact of bilaterally presented concentrations. When persons inhale a relatively strong irritant, such as the higher concentrations used here, they will exhibit a very brief reflex interruption of inhalation. An experiment on the threshold for the reflex implied that it too followed the Pythagorean rule of integration. This occurred for both males and females, though females displayed a lower threshold for the reflex, whether evoked unilaterally or bilaterally. This reflex may hold promise as an objective indicator of functional status of the nasal common chemical sense.

Perception of nasal pungency in smokers and nonsmokers.

Two experiments explored the difference in common chemical sensitivity between smokers and nonsmokers. The first experiment confirmed and extended our previous finding that smokers have a higher threshold than nonsmokers for a short-latency, reflex transitory apnea in response to a nasal irritant (carbon dioxide). The experiment revealed that even short periods of smoking (6-10 min) just before the measurement will further impair the smokers's sensitivity to an irritant. Application of the novel scaling technique magnitude matching, whereby persons judged the perceived magnitude of various levels of an irritant, odorant, and tone in the same session, implied that smokers actually perceive irritation less keenly than nonsmokers. The psychophysical functions for pungency in the two groups suggested that the insensitivity may arise from conductive factors (e.g., thickening of the mucus barrier) rather than from neural factors. The results of the scaling and those for the threshold for transitory apnea showed excellent quantitative agreement and indicated that the threshold for the reflex occurred at a criterion level of perceived pungency.