Dennis Shusterman

Chlorine inhalation produces nasal congestion in allergic rhinitics without mast cell degranulation

Seasonal allergic rhinitic (SAR) subjects are more sensitive to nasal irritants than nonrhinitic (NR) subjects; however, the mechanism underlying this difference is unclear. This study sought to determine whether irritant-induced nasal congestion involves mast cell degranulation. Eight SAR and eight NR subjects were exposed to both 1.0 parts per million chlorine and filtered air in separate visits; exposures were via nasal mask and lasted 15 min. Rhinomanometry was performed before, immediately after and 15 min after exposure. Following ≥2 weeks, exposures and symptom reporting were repeated with nasal lavage, rather than rhinomanometry, pre- and postexposure. A separate substudy using rye grass antigen provided a positive control. Mast cell tryptase was measured in nasal lavage fluid from both substudies using an automated fluoroenzyme immunoassay. Chlorine provocation significantly increased nasal airway resistance in SAR but not NR subjects. Conversely, tryptase levels in nasal lavage fluid were unaffected. Nasal allergen challenge significantly increased both nasal obstruction and nasal lavage tryptase in SAR subjects. Irritant-induced nasal congestion is more pronounced among seasonal allergic rhinitic than nonrhinitic subjects. However, unlike nasal allergen challenge, the mechanism of response to chlorine does not appear to involve mast cell degranulation.

Seasonal Allergic Rhinitic and Normal Subjects Respond Differentially to Nasal Provocation with Acetic Acid Vapor

Individuals with seasonal allergic rhinitis (SAR) showa more marked nasal obstructive response (increases in nasal airways resistance or NAR) after provocation with chlorine gas (Cl2) than do nonrhinitic (NR) controls. We were interested in learning whether similar differential respon-siveness was apparent after provocation with acetic acid vapor. Sixteen nonsmoking, nonasth-matic subjects, aged 21–63 yr, equally divided by gender and nasal allergy status, were enrolled in a single-blinded crossover study involving exposure to acetic acid (AA) vapor (15 ppm) or air for 15 min on separate days 1 wk apart. NAR was measured in triplicate before, immedi-ately post-, and 15 min postexposure, was normalized to baseline on a given exposure day, and was expressed as Net [NAR/baseline] after acetic acid versus control (air) exposure. After log transformation to achieve normality, the mean loge of Net [NAR/baseline] was 0.22 for SAR subjects and -0.11 for NR subjects immediately postexposure (p < .05); the corresponding values were 0.24 and -0.08, respectively, at 15 min postexposure (p < .05). Inhalation of acetic acid at the (NIOSH-recommended) short-term exposure limit of 15 ppm for 15 min produces differential nasal airflow obstruction among SAR versus NR subjects, with the former showing greater physiologic reactivity to this stimulus. This differential responsiveness is consistent with our previous findings with Cl2, indicating that there may be a generalized susceptibility factor associated with allergic rhinitis. The response occurs with slight subjective nasal irritation.

Predictors of Carbon Monoxide and Hydrogen Cyanide Exposure in Smoke Inhalation Patients

OBJECTIVE A prospective study of civilian (nonfirefighter) smoke inhalation patients was carried out to test the hypotheses that: 1) absorption of carbon monoxide and hydrogen cyanide from smoke can be predicted by clinical examination and historical data; and, more specifically 2) a history of exposure to burning synthetic polymers is an important predictor of systemic cyanide levels. METHODS The study was conducted over a three-year period at six urban hospitals. Patients with or without burns who were exposed to smoke within five hours of hospital arrival were sampled for carboxyhemoglobin, whole blood cyanide, urine cotinine and urine creatinine. Controls consisted of a smaller group of smoking status-matched, nonsmoke-exposed burn patients. ANALYSIS Historical information was obtained on SMOKING status, FIRETYPE (structural vs other), MATERIAL burned (natural vs synthetic) and LAGTIME (from exposure to sampling). A smoke inhalation SCORE (0-10) was assigned to each case, based on physical examination findings and changes on chest X ray, and carboxyhemoglobin and cyanide levels were entered into various multivariate linear regression models. RESULTS A total of 40 cases and 9 controls were recruited, ranging in age from 15 to 92 years. Thirty-four cases were discharged alive and six expired in-hospital. Observed carboxyhemoglobin levels ranged from 1.2% to 41.6% in cases (mean 8.6%), and from 0.5 to 7.3% in controls (mean 2.9%). Observed cyanide levels ranged from nondetectable (< 0.05 micrograms/mL) to 2.79 micrograms/mL in cases (mean 0.25 micrograms/mL), and from nondetectable to 0.11 micrograms/mL in controls (mean 0.03 micrograms/mL). Among cases, linear regression models explained up to 35% of the observed variance in carboxyhemoglobin levels (p < 0.001) and up to 48% of the variance in cyanide levels (p = 0.0001). CONCLUSIONS SCORE was the strongest predictor of both carboxyhemoglobin and cyanide levels; LAGTIME also explained significant variance for [log-transformed] carboxyhemoglobin. Historical factors, such as FIRETYPE, MATERIAL, and SMOKING status, did not explain significant variance in most of the statistical models employed.

A Device-Independent Evaluation of Carbonyl Emissions from Heated Electronic Cigarette Solvents

Objectives To investigate how the two main electronic (e-) cigarette solvents—propylene glycol (PG) and glycerol (GL)—modulate the formation of toxic volatile carbonyl compounds under precisely controlled temperatures in the absence of nicotine and flavor additives. Methods PG, GL, PG:GL = 1:1 (wt/wt) mixture, and two commercial e-cigarette liquids were vaporized in a stainless steel, tubular reactor in flowing air ranging up to 318°C to simulate e-cigarette vaping. Aerosols were collected and analyzed to quantify the amount of volatile carbonyls produced with each of the five e-liquids. Results Significant amounts of formaldehyde and acetaldehyde were detected at reactor temperatures ≥215°C for both PG and GL. Acrolein was observed only in e-liquids containing GL when reactor temperatures exceeded 270°C. At 318°C, 2.03±0.80 μg of formaldehyde, 2.35±0.87 μg of acetaldehyde, and a trace amount of acetone were generated per milligram of PG; at the same temperature, 21.1±3.80 μg of formaldehyde, 2.40±0.99 μg of acetaldehyde, and 0.80±0.50 μg of acrolein were detected per milligram of GL. Conclusions We developed a device-independent test method to investigate carbonyl emissions from different e-cigarette liquids under precisely controlled temperatures. PG and GL were identified to be the main sources of toxic carbonyl compounds from e-cigarette use. GL produced much more formaldehyde than PG. Besides formaldehyde and acetaldehyde, measurable amounts of acrolein were also detected at ≥270°C but only when GL was present in the e-liquid. At 215°C, the estimated daily exposure to formaldehyde from e-cigarettes, exceeded United States Environmental Protection Agency (USEPA) and California Office of Environmental Health Hazard Assessment (OEHHA) acceptable limits, which emphasized the need to further examine the potential cancer and non-cancer health risks associated with e-cigarette use.

Thirty Minute-Exposure to Aged Cigarette Smoke Increases Nasal Congestion in Nonsmokers

The aim of this study was to assess the effects of short exposures to experimentally aged cigarette smoke on the nose and upper airways. This crossover study compared the effects of 30-min exposures to (1) experimentally aged cigarette smoke at 1 mg/m3 particulate matter (PM)/14 ppm carbon monoxide (CO) and (2) conditioned filtered air on urinary metabolites of nicotine and tobacco-specific nitrosamines. Subjective nasal symptoms were assessed by questionnaire, objective nasal congestion was assessed by anterior rhinomanometry and nasal nitric oxide (NO) concentrations were determined. Experimentally aged cigarette smoke is a validated model for secondhand smoke (SHS). Twenty-six healthy nonsmokers (10 normal, 7 atopic/nonrhinitic, 7 atopic rhinitic, 2 nonatopic/rhinitic) were studied. A 30-min exposure to SHS increased nasal resistance in healthy nonsmokers. The rise in nasal resistance was most pronounced in rhinitic subjects. Significant increases were not noted when atopic subjects were considered independent of rhinitis status. Secondhand smoke exposure also elevated subjective nasal symptoms and urinary concentrations of metabolites of nicotine (cotinine and trans-3´-hydroxycotinine) and tobacco-specific nitrosamines [(4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL)] in all subgroups of subjects. Exposure-related, subjective nasal symptoms were significantly higher in rhinitic than in normal subjects. Significant changes in nasal NO concentrations were not detected. Data indicate a 30-min exposure to secondhand smoke at 1 mg/m3 PM increases subjective upper respiratory symptoms, increases urinary cotinine and NNAL, and produces objective nasal airflow obstruction in human subjects.

Occupational Rhinitis and Other Work-Related Upper Respiratory Tract Conditions

The nose and upper airways form the initial area of impact for air pollutants and allergens. The development of nasal allergies in the workplace (occupational rhinitis) may herald subsequent development of occupational asthma. Exposure controls, periodic surveillance, and early intervention may circumvent work-related airways disease and prevent unnecessary worker impairment and disability.

Methylene chloride intoxication in a furniture refinisher. A comparison of exposure estimates utilizing workplace air sampling and blood carboxyhemoglobin measurements.

A 35-year-old furniture refinisher came to the occupational medicine clinic with complaints of upper respiratory irritation, fatigue, and lightheadedness occurring on a daily basis after using a methylene chloride-containing paint stripper. Determinations of blood carboxyhemoglobin (COHb) on three occasions showed an apparently linear elevation of COHb as a function of hours worked on the day of sampling. COHb levels predicted from spot industrial hygiene measurements were in close concordance with those observed in the patient, indicating the potential usefulness of COHb monitoring in estimating airborne exposure levels. Methylene chloride (or dichloromethane) is an organic solvent that has found wide use as a degreaser, paint remover, aerosol propellant, and a blowing agent for polyurethane foams, and as a solvent in food processing, photographic film production, and plastics manufacturing. Discovery of its unusual metabolic fate--conversion to carbon monoxide in vivo--has earned the compound a special place in the solvent toxicology literature. Demonstration of oncogenicity in experimental animals has occasioned a reconsideration of exposure limits, with emphasis upon stricter controls. In some workplaces, conditions prevail in which controls are inadequate to prevent even acute toxicity, much less long-term exposure risks.

Pilot evaluation of the nasal nitric oxide response to humming as an index of osteomeatal patency.

Background Paranasal sinuses are reservoirs for nitric oxide (NO), and humming facilitates nasal diffusion of NO. The nasal NO response to humming has previously been shown to be blunted with chronic sinusitis and nasal polyposis. We hypothesized that the nasal NO response to humming will be proportional to radiographic osteomeatal patency when comparing allergic rhinitis (AR) patients (without chronic sinusitis) with normal controls. Methods Nonsmoking subjects completed questionnaires and skin-prick testing. Subjects underwent sinus CT scanning, followed by exhaled (oral) and nasal NO sampling (with and without humming). Humming-to-quiet (H/Q) nasal NO ratios were calculated. Three-dimensional reconstructions were used to trace the osteomeatal complex (OMC) and measure minimum cross-sectional area. Lund-Mackay scores were also documented. Results A total of 33 subjects (22 women; mean age, 35.5 years) completed the study. Seventeen AR patients (5 IAR and 12 PAR) participated, as did 16 nonallergic controls. Among controls, quiet nasal NO levels—corrected for fractional exhaled NO—rose significantly with OMC area and fell significantly with Lund-Mackay scores (p < 0.05). However, we observed no proportionality between H/Q ratio and radiographic OMC patency. Conclusion Analysis of nasal NO samples taken under quiet conditions from normal controls was consistent with the paranasal sinuses acting as a reservoir of nasal NO and with OMC patency acting as a significant factor in NO diffusion. However, our results did not support a relationship between the nasal NO response to humming and radiographic OMC patency in a sample excluding subjects with severe rhinosinusitis.

Acute-Onset Persistent Olfactory Deficit Resulting From Multiple Overexposures to Ammonia Vapor at Work

Impaired olfaction (a functional decrement in the sense of smell) is not uncommon. It is estimated that at least 2 million Americans suffer from an impaired sense of smell, although the actual number is probably higher. 1 The importance of this primary sense should in no way be minimized, since its absence can result in profound consequences. Both personal protection and quality of life can be compromised by impaired olfaction. Intact olfaction provides an excellent warning system for detection of hazardous conditions including smoke from fires, ingestion of spoiled foods, and hazardous materials encountered on the job. An employee lacking intact olfaction could be seriously impaired in certain settings, and indeed might be precluded from selected duties as a result. Even appropriate respiratory protection (ie, air-purifying respirators) might not offer sufficient assurance against toxic exposures because the impaired person would not be able to detect respirator leaks or cartridge breakthrough.2 The senses of taste and smell are intertwined; loss of smell can adversely affect gustatory pleasure or, more importantly, can lead to anorexia. Despite the frequency of irritant upper airway exposures occupationally,3 published cases of work-related residual olfactory impairment have frequently lacked documentation of sensory testing. Recognition of the link between irritant exposure and upper airway functional loss is thus important to occupational and general health practice. We report a case in which persistent hyposmia (reduction in the sense of smell) occurred following an acute industrial exposure to ammonia.

Symposium overview: Nasal trigeminal function: qualitative, quantitative, and temporal effects.

The nasal cavity is innervated by two cranial nerves: the olfactory (Cr. N. I) and the trigeminal (Cr. N. V). These structures together convey the sense of smell (I) and nasal pungency (V). These percepts are normally integrated in everyday life, as is implicit in references to, for example, “pungent odors.” Nasal pungency (often referred to as “irritation”) is an essential component of our response to foods, selected medications and cosmetics, and many air pollutants. Despite its obvious functional importance, however, nasal trigeminal function has commanded relatively modest scientific attention and resources, particularly when compared to its companion senses of smell and taste.1 The distinction between olfaction and nasal trigeminal chemoreception dates at least back to 1912, when Parker coined the term “common chemical sense” to describe the nonolfactory, nontaste chemical responsiveness of mucous membranes in vertebrates.2 Despite confusion regarding the word “common” (did it refer to the sensory apparatus or the nature of the stimuli?), the term continued to be used without serious debate at least until the 1960s. In 1964, Keele and Armstrong proposed the term “chemalgia,” highlighting the nociceptive nature of the sense.3 However, in 1990 Green