Trigeminally-mediated health effects of air pollutants: sources of inter-individual variability.

Trigeminal (ocular and nasal) irritation comprises the dominant symptom complex in so-called "problem buildings". Imputed etiologic agents in indoor air include extremes of temperature and humidity, the presence of volatile organic compounds, combustion products (including tobacco smoke), ozone (from office machines), and products of indoor air chemistry. In addition to producing primary irritation, mucosal irritants trigger a variety of secondary reflex symptoms, such as nasal congestion, rhinorrhea, and sinus pressure, and may predispose to infection in the form of sinusitis and otitis media. Marked variability in self-reported sensitivity to indoor air pollutants has been observed, with females, younger individuals, and people with allergies reporting more symptoms. We report on a series of experiments designed to uncover demographic patterns of "nasal irritant sensitivity", as well as potential mechanism(s) involved in observed chemesthetic variability.

Acute respiratory responses of the mouse to chlorine.

In human subjects 15-min exposure to 0.5-1.0 ppm chlorine gas causes a nasal obstructive response in the absence of a marked sensation of irritation. The current investigation was designed to assess the response of the mouse for comparative purposes. Respiratory physiological responses were measured in female C57Bl/6J mice exposed to 0.8 to 4.0 ppm chlorine gas. Chlorine was a potent sensory irritant with an RD50 of 2.3 ppm. The gas produced airway obstruction as indicated by a concentration-dependent increase in specific airways resistance (sRaw) during the 15-min exposure. At 0.8 ppm, chlorine produced only mild sensory irritation (<20% change in breathing frequency) and a 65% increase in sRaw. Pretreatment with atropine was without effect on the obstructive response, suggesting a lack of involvement of muscarinic cholinergic pathways. Pretreatment with the sensory nerve toxin, capsaicin, dramatically reduced both the sensory irritation and obstructive responses to chlorine, suggesting the involvement of sensory nerves. Studies were also performed using the surgically isolated upper respiratory tract of the anesthetized mouse. Chlorine was efficiently scrubbed from the airstream (>97%) in that site and produced an obstructive response that was of sufficient magnitude to account for the entire response observed in the intact animal. In summary, chlorine gas produces an immediate nasal obstructive response in the mouse that appears to be similar to that in the human.

Health effects of indoor odorants.

People assess the quality of the air indoors primarily on the basis of its odors and on their perception of associated health risk. The major current contributors to indoor odorants are human occupant odors (body odor), environmental tobacco smoke, volatile building materials, bio-odorants (particularly mold and animal-derived materials), air fresheners, deodorants, and perfumes. These are most often present as complex mixtures, making measurement of the total odorant problem difficult. There is no current method of measuring human body odor, other than by human panel studies of expert judges of air quality. Human body odors have been quantitated in terms of the "olf" which is the amount of air pollution produced by the average person. Another quantitative unit of odorants is the "decipol," which is the perceived level of pollution produced by the average human ventilated by 10 L/sec of unpolluted air or its equivalent level of dissatisfaction from nonhuman air pollutants. The standard regulatory approach, focusing on individual constituents or chemicals, is not likely to be successful in adequately controlling odorants in indoor air. Besides the current approach of setting minimum ventilation standards to prevent health effects due to indoor air pollution, a standard based on the olf or decipol unit might be more efficacious as well as simpler to measure.

Symptom prevalence and odor-worry interaction near hazardous waste sites.

Retrospective symptom prevalence data, collected from over 2000 adult respondents living near three different hazardous waste sites, were analyzed with respect to both self-reported "environmental worry" and frequency of perceiving environmental (particularly petrochemical) odors. Significant positive relationships were observed between the prevalence of several symptoms (headache, nausea, eye and throat irritation) and both frequency of odor perception and degree of worry. Headaches, for example, showed a prevalence odds ratio of 5.0 comparing respondents who reported noticing environmental odors frequently versus those noticing no such odors and 10.8 comparing those who described themselves as "very worried" versus "not worried" about environmental conditions in their neighborhood. Elimination of respondents who ascribed their environmental worry to illness in themselves or in family members did not materially affect the strength of the observed associations. In addition to their independent effects, odor perception and environmental worry exhibited positive interaction as determinants of symptom prevalence, as evidenced by a prevalence odds ratio of 38.1 comparing headaches among the high worry/frequent-odor group and the no-worry/no-odor group. In comparison neighborhoods with no nearby waste sites, environmental worry has been found to be associated with symptom occurrence as well. Potential explanations for these observations are presented, including the possibility that odors serve as a sensory cue for the manifestation of stress-related illness (or heightened awareness of underlying symptoms) among individuals concerned about the quality of their neighborhood environment.

Hypotheses to explain the higher symptom rates observed around hazardous waste sites.

Five studies were carried out around hazardous waste sites in California in which the main route of exposure was to low-level parts per billion concentrations of either gaseous emissions or airborne dust particles. Although there was no evidence suggesting excesses in cancer or birth defects, the total number and the prevalence of many of subjective symptoms were higher in areas near the site than in control neighborhoods. We discuss a number of causal processes that could explain these results. We conclude that a classical toxicological response and mass psychogenic illness are not valid explanations. Recall bias may explain part of the pattern. We present data from situations where stress alone from environmental anxiety has produced a similar magnitude of excess symptoms in populations. The fact that excess symptoms in waste site neighbors is found primarily in those who complain of odors or who are worried about environmental chemicals suggests the possibility that autonomic, stress-mediated mechanisms or behavioral sensitization are active in the genesis of these symptoms. A variety of confounders were controlled for. The hypothesis that chemically "acquired immune deficiency" can cause subtle symptomatology as a prodrome to subsequent serious disease has been raised in testimony at several toxic tort trials about waste sites. Although this hypothesis seems unlikely, particularly at sites such as the ones we studied with low airborne exposures, if true it would have profound regulatory implications.

The influence of sex, allergic rhinitis, and test system on nasal sensitivity to airborne irritants: a pilot study.

"Nasal irritant sensitivity" is an important construct in environmental health science; functional measures, however, lack standardization. We performed duplicate measures of nasal irritant perceptual acuity on 16 subjects (evenly divided by sex and seasonal allergy status) using two different test compounds: carbon dioxide (CO2) (detection) and n-propanol (localization). The a priori hypotheses included a) allergic rhinitics will display lower perceptual thresholds than nonrhinitics; b) females will display lower perceptual thresholds than males; and c) estimates of perceptual acuity using the two test systems will be positively correlated. We obtained CO2 detection thresholds using an ascending concentration series, presenting 3-sec pulses of CO2, paired with air in random order, by nasal cannula. We obtained localization thresholds by simultaneously presenting stimuli (ascending concentrations of n-propanol vapor in air) and blanks (saturated water vapor in air) to opposite nostrils, with laterality randomized. In terms of test-retest reliability, individual replicate measures for CO2 detection thresholds correlated more closely than did the localization thresholds of volatile organic compounds (VOC) (r = 0.65 and r = 0.60, respectively). As an intertest comparison, log-transformed individual mean CO2 and VOC measures were positively correlated with an r of 0.63 (p < 0.01). In univariate analyses, sex predicted both log-transformed CO2 and VOC thresholds (females being more "sensitive"; p < 0.05 and 0.001, respectively). Nasal allergies predicted sensory testing results only in the multivariate analysis, and then only for VOC localization (p < 0.05). The question of population variation in nasal irritant sensitivity (as well as the generalizability of results across test compounds) deserves further attention.

Persistent respiratory health effects after a metam sodium pesticide spill.

STUDY OBJECTIVE: To report the occurrence of persistent respiratory disorders, including irritant-induced asthma, among adults living and working near an environmental spill of the pesticide, metam sodium, after the derailment of a tank car. DESIGN: Retrospective clinical case series. SETTING: California communities situated within one-half mile of the Sacramento River, from Mt. Shasta City to Shasta Lake. PATIENTS: 197 adults referred to a university occupational/environmental health clinic or to a private occupational/environmental health practitioner for evaluation of health problems potentially related to the spill. MEASUREMENTS AND RESULTS: History, physical examination, review of medical records, spirometry, and methacholine challenge testing revealed 20 cases of persistent irritant-induced asthma and 10 cases of persistent exacerbation of asthma. CONCLUSIONS: This is the first reported series of cases of persistent irritant-induced asthma involving both community residents and occupationally exposed individuals.

Usefulness of computed tomographic scan in the evaluation of sensorineural hearing loss in children.

A retrospective chart study was conducted to determine the diagnostic yield of temporal bone imaging for children with sensorineural hearing loss of unknown cause. Seventy consecutive cases, spanning 4.5 years, were identified and individual computed tomography films reviewed. Cases were analyzed with respect to patients' age, duration of hearing loss, sudden onset vs progressive loss, unilateral vs bilateral, and other symptoms. Of the 70 computed tomographic scans, nine showed temporal bone or other intracranial abnormalities. The majority of these findings were localized to structures in the posterior and middle cranial fossae. No eight nerve tumors were identified. Congenital hearing loss and hearing loss secondary to viral infections are the most common cause of sensorineural hearing loss when discovered in early childhood and, often, have no radiographic abnormality. The decision to explore an ear for a presumed perilymph fistula is based almost exclusively on the history and physical examination, and not on the demonstration of any radiographic findings. For the children presenting with stable hearing impairment in the absence of other findings, computed tomographic scans were either negative or did not contribute to diagnosis. Since tumors of the eighth nerve are rare in children under 16 years of age (without neurofibromatosis), and radiologic studies have a low yield in identifying perilymph fistulas, the routine use of computed tomographic imaging in such children may be unjustified.

Unintentional carbon monoxide deaths in California from charcoal grills and hibachis.

This study was carried out to determine the annual incidence rate of and factors associated with unintentional deaths due to carbon monoxide (CO) poisoning from charcoal grills/hibachis in California during 1979-1988. A search through the California Master Mortality File was conducted to identify all cases with ICD-9 codes related to unintentional CO deaths. Individual coroners' investigation reports were obtained from 42 counties and evaluated by three evaluators. After excluding miscoded and misclassified cases, 444 deaths were judged to be authentic cases of unintentional CO poisoning. Among them, 59 deaths found to be due to the improper use of charcoal grills/hibachis. An increasing but not statistically significant trend was observed over the 10-year period. The highest rates occurred among males, asians, blacks, and middle-aged (20-39) people. Fifty-four percent of the deaths occurred in motor vehicles and 46% in residential structures.

Medical causation analysis heuristics.

Medical causation analysis determines whether or not a specific patient's illness is the result of a work site or an environmental exposure. In the past, this has been conducted implicitly with little analysis of the process per se. Our review suggests that there are several distinct heuristics that may be utilized; these include probability-based models, application of group-based data (epidemiology) to individuals, Bayesian analysis, a priori assumptions about which conclusions are better, and others. Some methods consider only work causes, whereas others explicitly consider alternative explanations. There are considerable differences among the methods in process, outcome, and fundamental assumptions. Formal assessment of the medical causation analysis process can provide insight and may ultimately lead to its standardization and improvement.

Chest wall pain and possible rhabdomyolysis after chloropicrin exposure. A case series.

Three cases are summarized in which persistent chest wall pain, as well as elevations of creatine phosphokinase (CK) levels, occurred after exposure to chloropicrin vapor in an agricultural chemicals facility. Both the severity of the symptoms and the degree of biochemical abnormality appeared to follow a dose-response relationship. Myoglobinuria, on the other hand, was not found. Elevation of CK after chloropicrin exposure has not previously been reported and may represent low-grade rhabdomyolysis. Workups performed after symptomatic chloropicrine exposure should include CK-level determination.

Critical review: the health significance of environmental odor pollution.

Environmental odor pollution problems generate a significant fraction of the publicly initiated complaints received by air pollution control districts. Such complaints can trigger a variety of enforcement activities under existing state and local statutes. However, because of the frequently transient timing of exposures, odor sources often elude successful abatement. Furthermore, because of the predominantly subjective nature of associated health complaints, air pollution control authorities may predicate their enforcement activities upon a judgment of the public health impact of the odor source. Noxious environmental odors may trigger symptoms by a variety of physiologic mechanisms, including exacerbation of underlying medical conditions, innate odor aversions, aversive conditioning phenomena, stress-induced illness, and possible pheromonal reactions. Whereas relatively consistent patterns of subjective symptoms have been reported among individuals who live near environmental odor sources, documentation of objective correlates to such symptoms would require as-yet unproven research tools. Therefore, given our current state of knowledge, any differential regulatory response to environmental odor pollution, which is based upon the distinction between community "annoyance reactions" and "health effects," is a matter of legal--not scientific--interpretation.

Measurement of nasal irritant sensitivity to pulsed carbon dioxide: a pilot study.

Nasal irritation and associated symptoms (e.g., nasal congestion, rhinorrhea, sinus headache) are important air-pollution-related health complaints, particularly in so-called problem buildings. Individual differences in nasal irritant sensitivity are therefore of both clinical and regulatory interest. To document such differences, one must first functionally define perceptual acuity to airborne irritants. In an adaptation of an established sensory testing method, the authors used the odorless irritant carbon dioxide in an electronically controlled dilution apparatus to deliver brief (approximately 3 s) pulses at controlled levels (10%-70%, vol/vol), synchronized with the inspiratory phase of the respiratory cycle. Investigators who use this apparatus can use a variant of the forced-choice paradigm for threshold determination to document nasal irritant sensitivity. The authors recruited 30 adult volunteers (17 males, 13 females; average age = 41 y, range = 19-79 y) from a university laboratory complex and from the general community. Within this group, there was a skewed distribution of carbon dioxide thresholds (arithmetic mean = 28%, geometric mean = 27% [vol/vol]). In univariate analyses, geometric mean carbon dioxide thresholds differed significantly with respect to smoking status (36% carbon dioxide in smokers versus 25% in nonsmokers; p < .005), but not with respect to age, gender, or self-reported history of allergic rhinitis. In a multivariate analysis, gender also approached significance; females tended to show better perceptual acuity than males (p = .06). Neither self-reported "vasomotor rhinitis" symptoms nor self-reported symptomatic reactivity to environmental tobacco smoke predicted carbon dioxide thresholds. Pulsed carbon dioxide is well tolerated by subjects who participate in a threshold detection task; the procedure yields a potential endpoint with which to compare individuals (and groups) with respect to nasal irritant perceptual acuity. The relationship between such acuity and nasal physiologic reactivity-as well as the generalizability of such measures to other, more environmentally realistic irritants-has yet to be defined.

Work-related asthma and latex allergy. Sorting out the types, causes, and consequences.

Work-related asthma now has clear definitions based on criteria agreed upon by the American College of Chest Physicians. The clinician should suspect occupational asthma, irritant-induced asthma, or work-aggravated asthma in adults with new-onset asthma or asthma symptoms that worsen during work, after work (late allergic response), or over the course of workdays. The possible cause should be sought, and a skin test or immunoassay should be performed, if possible,to he;lp detect sensation. Workup als o includes objective documentation of worsening of symptoms and airway obstruction during occupational exposure. If this information is inconclusive, an inhalation challenge may be considered. Medical management is the same as for nonoccupational asthma, but cessation of exposure to the specific agent is necessary to improve long-term diagnosis. Latex allergy and latex-induced asthma are becoming more common in the workplace, particularly in the healthcare field. No commercially available standard serum or skin test are available for diagnosis. The principal treatment is avoidance of latex, which can be achieved in most cases without extensive changes to the workplace.

Problem-solving techniques in occupational medicine.

The diagnosis of occupational illnesses may be considerably more difficult than is the case with occupational injuries because of a variety of factors: an intervening latency period, uncertainty in identifying the most significant chemical or physical exposures, determination of exposure levels retrospectively, and coordination of the physician with regulatory and workers' compensation bureaucracies. Such problem-solving techniques as retrospective industrial hygiene and attention to in-situ chemistry can act as means of reducing the uncertainty in making the diagnosis of occupational illness. Advance familiarity with workers' compensation and state or federal regulatory agencies can further facilitate diagnosis and patient advocacy.

Nasal hyperreactivity in allergic and non-allergic rhinitis: a potential risk factor for non-specific building-related illness.

UNLABELLED: Self-reported non-allergic nasal symptom triggers in non-allergic ('vasomotor') rhinitis overlap with commonly identified environmental exposures in non-specific building-related illness. These include extremes of temperature and humidity, cleaning products, fragrances, and tobacco smoke. Some individuals with allergic rhinitis also report non-allergic triggers. We wished to explore the phenotypic overlap between allergic and non-allergic rhinitis by ascertaining self-reported non-allergic nasal symptom triggers among allergic rhinitics. Sixty subjects without work-related respiratory exposures or symptoms, aged 19-68 years, stratified by age, gender and (skin test-proven) allergic rhinitis status, were queried with regard to self-reported non-allergic nasal symptom triggers (aggregate score 0-8). In this sample, the number of self-reported non-allergic triggers was bimodal, with peaks at 1 and 5. Forty-two percent of seasonal allergic rhinitic subjects reported more than three non-allergic triggers, compared with only 3% of non-allergic non-rhinitics (P < 0.01). Subjects over 35 years were more likely to report one or more non-allergic triggers, particularly tobacco smoke (P < 0.05). Allergic rhinitics reported more non-allergic symptom triggers than did non-allergic, non-rhinitics. As indexed by self-reported reactivity to non-specific physical and chemical triggers, both non-allergic rhinitics and a subset of allergic rhinitics may constitute susceptible populations for non-specific building-related illness. PRACTICAL IMPLICATIONS: Judging by self-report, a substantial subset of individuals with allergic rhinitis--along with all individuals with nonallergic rhinitis (by definition)--are hyperreactive to non-allergic triggers. There is overlap between these triggers (elicited in the process of obtaining a clinical diagnosis) and environmental characteristics associated with ''problem buildings.'' Since individuals with self-identified rhinitis report an excess of symptoms in most epidemiologic studies of problem buildings (even in the absence of unusual aeroallergen levels), rhintics may be acting as a ''sentinel'' subgroup when indoor air quality is suboptimal. Together, non-allergic rhinitics plus allergic rhinitics with prominent non-allergic triggers, are thought to constitute approximately one-sixth of the US population.

Documentation of the nasal nitric oxide response to humming: methods evaluation.

RATIONALE: Nitric oxide (NO) is present at higher concentrations in the nasal cavity than in the lower airway, and at even higher concentrations within the paranasal sinuses proper. When the paranasal sinus ostia are patent, acoustic activity produced by vocalization with closed lips (humming) promotes mixing of sinus with nasal gases, producing a further increase in nasal NO. We wished to evaluate procedures for the documentation of the nasal NO response to humming. MATERIALS AND METHODS: We compared two ATS-recommended sampling methods: 1) active exhalation of lower airway gas (parallel technique) and 2) passive aspiration of nasal gas with closed velopharynx (series technique). Variables controlled for included sampling rate, external resistance (parallel method), humming frequency, humming duration, and intertrial interval. Prior to upper airway sampling, exhaled lower airway NO was determined utilizing ATS-standardized technique. RESULTS: Ten volunteers (seven males and three females, aged 21-58) with no history of respiratory allergies or sino-nasal disease were studied in a single session each. The parallel technique documented an increase in nasal NO during the humming manoeuvre in all subjects (mean ratio of humming-to-quiet NO, 4.2), whereas the series technique did so in eight of 10 subjects (mean ratio 2.1). Correcting for admixture from the lower airway, the ratio of humming-to-quiet NO was greater with the parallel than series sampling technique (P < 0.05). CONCLUSIONS: Documentation of the response of nasal NO to humming in subjects without sino-nasal disease was consistently achievable by parallel sampling using commercially available equipment. Specific operational procedures are proposed.