History of pollutant adjuvants in respiratory allergy.

Combined exposures to allergens and air pollutants emerged as a topic of concern in scientific circles by the 1980's, when it became clear that parallel increases in respiratory allergies and traffic-related air pollution had been occurring during the 20th century. Although historically there has been a tendency to treat exposure-related symptoms as either allergic or toxicologic in nature, cross-interactions have since been established between the two modalities. For example, exposure to selected air pollutants in concert with a given allergen can increase the likelihood that an individual will become sensitized to that allergen, strongly suggesting that the pollutant acted as an adjuvant. Although not a review of underlying mechanisms, the purpose of this mini-review is to highlight the potential significance of co-exposure to adjuvant chemicals in predicting allergic sensitization in the respiratory tract. The current discussion emphasizes the upper airway as a model for respiratory challenge studies, the results of which may be applicable-not only to allergic rhinitis-but also to conjunctivitis and asthma.

Relationships between GABA, glutamate, and GABA/glutamate and social and olfactory processing in children with autism spectrum disorder.

Theories of altered inhibitory/excitatory signaling in autism spectrum disorder (ASD) suggest that gamma amino butyric acid (GABA) and glutamate (Glu) abnormalities may underlie social and sensory challenges in ASD. Magnetic resonance spectroscopy was used to measure Glu and GABA+ levels in the amygdala-hippocampus region and cerebellum in autistic children (n = 30), a clinical control group with sensory abnormalities (SA) but not ASD (n = 30), and children with typical development (n = 37). All participants were clinically assessed using the Autism Diagnostic Interview-Revised, the Autism Diagnostic Observation Scale-2, and the Child Sensory Profile-2. The Social Responsiveness Scale-2, Sniffin Sticks Threshold Test, and the University of Pennsylvania Smell Identification Test were administered to assess social impairment and olfactory processing. Overall, autistic children showed increased cerebellar Glu levels compared to TYP children. Evidence for altered excitatory/inhibitory signaling in the cerebellum was more clear-cut when analyses were restricted to male participants. Further, lower cerebellar GABA+/Glu ratios were correlated to more severe social impairment in both autistic and SA males, suggesting that the cerebellum may play a transdiagnostic role in social impairment. Future studies of inhibitory/excitatory neural markers, powered to investigate the role of sex, may aid in parsing out disorder-specific neurochemical profiles.

Trigeminal Function in Sino-Nasal Health and Disease.

The upper airway (nasal passages, paranasal sinuses, pharynx, and glottis) provides the sentinel portion of the human respiratory tract, with the combined senses of olfaction (cranial nerve I) and trigeminal sensation (cranial nerve V) signaling the quality of inspired air. Trigeminal function also complements the sense of taste (in turn mediated by cranial nerves VII, IX and X), and participates in the genesis of taste aversions. The ability of trigeminal stimulation in the upper aero-digestive tract to trigger a variety of respiratory and behavioral reflexes has long been recognized. In this context, the last three decades has seen a proliferation of observations at a molecular level regarding the mechanisms of olfaction, irritation, and gustation. Concurrently, an ever-widening network of physiological interactions between olfaction, taste, and trigeminal function has been uncovered. The objective of this review is to summarize the relatively recent expansion of research in this sub-field of sensory science, and to explore the clinical and therapeutic implications thereof.

Nasal nitric oxide flux from the paranasal sinuses.

PURPOSE OF REVIEW: Upper airway nitric oxide (NO) is physiologically important in airway regulation and defense, and can be modulated by various airway inflammatory conditions, including allergic rhinitis and chronic rhinosinusitis - with and without polyposis. Paranasal sinuses serve as a NO 'reservoir', with concentrations typically exceeding those measured in lower airway (fractional exhaled NO or FeNO) by a few orders of magnitude. However, the dynamics of NO flux between the paranasal sinuses and main nasal airway, which are critical to respiratory NO emission, are poorly understood. RECENT FINDINGS: Historically, NO emissions were thought to be contributed mostly by the maxillary sinuses (the largest sinuses) and active air movement (convection). However, recent anatomically-accurate computational modeling studies based on patients' CT scans showed that the ethmoid sinuses and diffusive transport dominate the process. SUMMARY: These new findings may have a substantial impact on our view of nasal NO emission mechanisms and sinus physiopathology in general.

Use of computational fluid dynamics (CFD) to model observed nasal nitric oxide levels in human subjects.

BACKGROUND: Upper airway nitric oxide (NO) is physiologically important in airway regulation and defense, and nasal NO (nNO) levels typically exceed those in exhaled breath (fractional exhaled NO [FeNO]). Elevated concentrations of NO sampled from the nose, in turn, reflect even higher concentrations in the paranasal sinuses, suggesting a "reservoir" role for the latter. However, the dynamics of NO flux within the sinonasal compartment are poorly understood. METHODS: Data from 10 human subjects who had previously undergone both real-time nNO sampling and computed tomography (CT) scanning of the sinuses were analyzed using computational fluid dynamics (CFD) methods. Modeled and observed nNO values during the initial 2-s transient ("spike") during nasal exhalation were then compared. RESULTS: Examining the initial 2-s transient spike for each subject (as well as the pooled group), there was a statistically significant correlation between modeled and observed nNO levels, with r values ranging from 0.43 to 0.89 (p values ranging from <0.05 to <0.0001). Model performance varied between subjects, with weaker correlations evident in those with high background (FeNO) levels. In addition, the CFD simulation suggests that ethmoid sinuses (>60%) and diffusion process (>54%) contributed most to total nasal NO emissions. CONCLUSION: Analysis of this dataset confirms that CFD is a valuable modeling tool for nNO dynamics, and highlights the importance of the ethmoid sinuses, as well as the role of diffusion as an initiating step in sinonasal NO flux. Future model iterations may apply more generally if baseline FeNO is taken into account.

Seroprevalence of SARS-CoV-2 Among Firefighters/Paramedics in San Francisco, CA.

OBJECTIVES: Despite having close contact with the general public, members of the San Francisco Fire Department (SFFD) reported relatively few cases of COVID-19 during the first half of 2020. Our objective was to explore evidence for prior undetected infections by conducting a seroprevalence survey, and to document both risk and protective factors for prior COVID-19 infection. METHODS: This cross-sectional study assessed workplace practices and exposures of SFFD personnel during the first 6 months of 2020 via questionnaire and documented prior COVID-19 infections by serologic antibody testing using an orthogonal testing protocol. RESULTS: Of 1231 participating emergency responders, three (0.25%) had confirmed positive COVID-19 antibody results. CONCLUSIONS: Safe workplace practices, community public health intervention, and low community infection rates appear to have been protective factors for emergency responders in San Francisco during our study period.

Computational modeling of nasal nitric oxide flux from the paranasal sinuses: Validation against human experiment.

BACKGROUND: Nitric oxide (NO) is important in respiratory physiology and airway defense. Although the paranasal sinuses are the major source of nasal NO, transport dynamics between the sinuses and nasal cavities are poorly understood. METHODS: Exhaled nasal NO tracings were measured in two non-asthmatic subjects (one with allergic rhinitis, one without) using NO analyzer connected via face mask. We subsequently performed computational fluid dynamics NO emission simulations based on individual CT scans and compared to the experimental data. RESULTS: Simulated exhaled NO tracings match well with experimental data (r > 0.84, p < 0.01) for both subjects, with measured peaks reaching 319.6 ppb in one subject (allergic-rhinitis), and 196.9 ppb in the other. The CFD simulation accurately captured the peak differences, even though the initial sinus NO concentration for both cases was set to the same 9000 ppb based on literature value. Further, the CFD simulation suggests that ethmoid sinuses contributed the most (>67%, other sinuses combined <33%) to total nasal NO emission in both cases and that diffusion contributes more than convective transport. By turning off diffusion (setting NO diffusivity to ~0), the NO emission peaks for both cases were reduced by >70%. CONCLUSION: Historically, nasal NO emissions were thought to be contributed mostly by the maxillary sinuses (the largest sinuses) and active air movement (convection). Here, we showed that the ethmoid sinuses and diffusive transport dominate the process. These findings may have a substantial impact on our view of nasal NO emission mechanisms and sinus physiopathology in general.

Assessment of Methylene Chloride-Related Fatalities in the United States, 1980-2018.

Importance: Methylene chloride is a halogenated organic solvent widely used in paint strippers, cleaners, adhesives, and sealants. Despite label warnings and occupational standards, methylene chloride-related fatalities continue to occur in the United States. Objective: To identify and analyze methylene chloride-related fatalities in the US. Design, Setting, and Participants: For this case series, we conducted systematic searches of sources, including PubMed and government databases, for unintentional fatalities in the US that were associated with exposure to methylene chloride or products containing methylene chloride between 1980 and 2018. We reviewed all available information, including inspection reports, autopsy reports, and medical records; data analyses were conducted from August 2018 to August 2020. Cases were categorized as those occurring in the home (consumer deaths) or at work (occupational deaths). Exposures: Methylene chloride or products containing methylene chloride. Main Outcomes and Measures: To determine characteristics of the methylene chloride-related fatalities, we recorded demographic information; the setting; circumstances, including information on safety measures used, if available; and products used. Where medical records were available, we recorded toxicology results and autopsy findings. We also obtained data about nonfatal methylene chloride cases from the American Association of Poison Control Centers. Results: From 1980 to 2018, 85 methylene chloride-related fatalities were identified in the US, including 74 (87%) in occupational settings; of those who died, 75 (94%) were men, and for the 70 cases with available information, the median (interquartile range) age of the decedents was 31 (24-46) years. Paint strippers were the most common products involved in methylene chloride-related fatalities (n = 60). The proportion of occupational fatalities related to paint stripping increased from 22 (55%) before 2000 to 30 (88%) after 2000. Similarly, occupational fatalities associated with bathtub or paint stripping in bathrooms increased from 2 (5%) before 2000 to 21 (62%) after 2000. From 1985 to 2017, the American Association of Poison Control Centers documented 37 201 nonfatal methylene chloride cases, with a decrease in the annual number of cases starting in the late 1990s. Conclusions and Relevance: Results of this case series demonstrated that despite regulations to address the toxic effects of methylene chloride use for consumers and workers, there are continuing fatalities in the US, particularly in occupational settings. Prevention of fatalities associated with methylene chloride exposure should emphasize the use of safer substitutes, rather than hazard warnings or reliance on personal protective equipment.

Solvent-based paint and varnish removers: a focused toxicologic review of existing and alternative constituents.

Paint and varnish removers constitute a major potential source of organic solvent exposure to contractors and home improvement enthusiasts. Unfortunately, the leading paint remover formulations have traditionally contained, as major ingredients, chemicals classified as probable human carcinogens (eg, methylene chloride) or reproductive toxicants (eg, N-methylpyrrolidone). In addition, because of its unique toxicology (ie, hepatic conversion to carbon monoxide compounding generic solvent narcosis and arrythmogenesis), high volatility, and rigorous requirements for personal protective equipment, methylene chloride exposures from paint removers have been linked to numerous deaths involving both occupational and consumer usage. The aim of this review is to summarize the known toxicology of solvent-based paint remover constituents (including those found in substitute formulations) in order to provide health risk information to regulators, chemical formulators, and end-users of this class of products, and to highlight any data gaps that may exist.

Association of Allergic Rhinitis With Change in Nasal Congestion in New Continuous Positive Airway Pressure Users.

Importance: Nasal congestion occurring after continuous positive airway pressure (CPAP) treatment initiation impairs CPAP adherence. Allergic rhinitis is associated with worsening nasal congestion in patients who are exposed to nonallergic triggers. Use of CPAP presents potential nonallergic triggers (eg, humidity, temperature, pressure, and airflow). Objective: To compare nasal congestion among CPAP users with allergic rhinitis, nonallergic rhinitis, and no rhinitis. We hypothesize that CPAP patients with baseline allergic rhinitis are more likely to experience a worsening of nasal congestion (or less improvement in nasal congestion) compared with patients with no baseline rhinitis. Design, Setting, and Participants: This prospective cohort study included consecutive patients newly diagnosed with obstructive sleep apnea in a tertiary sleep center who were using CPAP therapy 3 months after diagnosis. Baseline rhinitis status was assigned as allergic rhinitis, nonallergic rhinitis, or no rhinitis, based on questionnaire responses and past allergy testing. Data were collected from 2004 to 2008 and analyzed from July 2019 to February 2020. Main Outcomes and Measures: At baseline before CPAP exposure and again 3 months later, subjective nasal congestion was measured with the Nasal Obstruction Symptom Evaluation (NOSE) scale and a visual analog scale (VAS), each scored from 0 to 100 (100 = worst congestion). Changes in nasal congestion were tested over 3 months for the whole cohort, within each rhinitis subgroup (paired t test), and between rhinitis subgroups (multivariate linear regression). Results: The study cohort comprised 102 participants, of whom 61 (60%) were male and the mean (SD) age was 50 (13). The study included 23 (22.5%) participants with allergic rhinitis, 67 (65.7%) with nonallergic rhinitis, and 12 (11.8%) with no rhinitis. Nasal congestion improved from baseline to 3 months in the whole cohort (mean [SD] NOSE score, 38 [26] to 27 [23], mean [SD] change, -10 [23]; 95% CI, -15 to -6; mean [SD] VAS score, 41 [27] to 32 [28]; mean [SD] change, -10 [26]; 95% CI, [-15 to -4]) and in each rhinitis subgroup. Adjusted improvement in nasal congestion at 3 months was significantly less in the allergic rhinitis subgroup compared with the no rhinitis subgroup (positive difference means less improvement) compared with baseline: NOSE score 14 (95% CI, 1 to 28) and VAS score 15 (95% CI, 0 to 30). Conclusions and Relevance: Initiation of CPAP was associated with improved subjective nasal congestion, but less improvement in patients with baseline allergic rhinitis. Baseline allergic rhinitis may predict which patients are more vulnerable to potential congestive effects of CPAP.

FMRI correlates of olfactory processing in typically-developing school-aged children.

Human olfactory processing is understudied relative to other sensory modalities, despite its links to neurodevelopmental and neurodegenerative disorders. To address this limitation, we developed a fast, robust fMRI odor paradigm that is appropriate for all ages and levels of cognitive functioning. To test this approach, thirty-four typically developing children aged 7-12 underwent fMRI during brief, repeated exposure to phenylethyl alcohol, a flower-scented odor. Prior to fMRI scanning, olfactory testing (odor detection and identification) was conducted. During fMRI stimulus presentation, odorant release was synchronized to each participant's inspiratory phase to ensure participants were inhaling during the odorant exposure. Between group differences and correlations between activation and odor detection threshold scores were tested using the FMRIB Software Library. Results demonstrated that our 2-min paradigm significantly activated primary and secondary olfactory regions. In addition, a significant relationship between odor detection threshold and higher activation in the right amygdala and lower activation in the left frontal, insular, occipital, and cerebellar regions was observed, suggesting that this approach is sensitive to individual differences in olfactory processing. These findings demonstrate the feasibility of studying olfactory function in children using brain imaging techniques.

Measurement of heating coil temperature for e-cigarettes with a "top-coil" clearomizer.

OBJECTIVES: To determine the effect of applied power settings, coil wetness conditions, and e-liquid compositions on the coil heating temperature for e-cigarettes with a "top-coil" clearomizer, and to make associations of coil conditions with emission of toxic carbonyl compounds by combining results herein with the literature. METHODS: The coil temperature of a second generation e-cigarette was measured at various applied power levels, coil conditions, and e-liquid compositions, including (1) measurements by thermocouple at three e-liquid fill levels (dry, wet-through-wick, and full-wet), three coil resistances (low, standard, and high), and four voltage settings (3-6 V) for multiple coils using propylene glycol (PG) as a test liquid; (2) measurements by thermocouple at additional degrees of coil wetness for a high resistance coil using PG; and (3) measurements by both thermocouple and infrared (IR) camera for high resistance coils using PG alone and a 1:1 (wt/wt) mixture of PG and glycerol (PG/GL). RESULTS: For single point thermocouple measurements with PG, coil temperatures ranged from 322 ‒ 1008°C, 145 ‒ 334°C, and 110 ‒ 185°C under dry, wet-through-wick, and full-wet conditions, respectively, for the total of 13 replaceable coil heads. For conditions measured with both a thermocouple and an IR camera, all thermocouple measurements were between the minimum and maximum across-coil IR camera measurements and equal to 74% ‒ 115% of the across-coil mean, depending on test conditions. The IR camera showed details of the non-uniform temperature distribution across heating coils. The large temperature variations under wet-through-wick conditions may explain the large variations in formaldehyde formation rate reported in the literature for such "top-coil" clearomizers. CONCLUSIONS: This study established a simple and straight-forward protocol to systematically measure e-cigarette coil heating temperature under dry, wet-through-wick, and full-wet conditions. In addition to applied power, the composition of e-liquid, and the devices' ability to efficiently deliver e-liquid to the heating coil are important product design factors effecting coil operating temperature. Precautionary temperature checks on e-cigarettes under manufacturer-recommended normal use conditions may help to reduce the health risks from exposure to toxic carbonyl emissions associated with coil overheating.

Occupational rhinitis and occupational asthma: Association or progression?

BACKGROUND: Occupational asthma is the most frequently reported occupational respiratory disease in registries, and is often co-diagnosed with occupational rhinitis. We undertook a systematic review of the English-language epidemiologic literature linking these two conditions, with emphasis on progression from occupational rhinitis to occupational asthma. METHODS: PubMed and Embase were queried in a series of structured searches designed to identify studies comparing occupational asthma and occupational rhinitis incidence or prevalence in occupationally exposed individuals. RESULTS: The searches yielded a total of 109 unique citations, 15 of which yielded inferential data on the occupational rhinitis-asthma relationship. Nine of fifteen studies showed statistically significant associations between the occurrence of occupational rhinitis and occupational asthma among individual workers. CONCLUSIONS: Limited data support the notion that occupational rhinitis precedes the development of occupational asthma, particularly when high-molecular-weight (HMW) agents are involved. The relationship between the two conditions could not be evaluated in many relevant studies due to a lack of cross-tabulation of individual cases.

Dust Exposure and Coccidioidomycosis Prevention Among Solar Power Farm Construction Workers in California.

OBJECTIVES: To investigate if work activities, dust exposure, and protection measures were associated with a 2011 to 2014 coccidioidomycosis outbreak among workers constructing 2 solar farms in California. METHODS: In 2013, we mailed self-administered questionnaires to employees who were onsite at the solar farms where the outbreak occurred to identify cases of clinical coccidioidomycosis and compare with asymptomatic workers by using multivariate logistic regression. RESULTS: When we compared 89 workers with clinical coccidioidomycosis to 325 asymptomatic workers, frequently being in a dust cloud or storm (odds ratio [OR] = 5.93; 95% confidence interval [CI] = 3.18, 11.06) significantly increased the odds of clinical coccidioidomycosis, whereas frequently wetting soil before soil-disturbing activity (OR = 0.42; 95% CI = 0.24, 0.75) was protective. When we controlled for being in a dust cloud or storm, frequent soil disturbance significantly increased the odds of clinical coccidioidomycosis only among those who reported wearing a respirator infrequently (OR = 2.31; 95% CI = 1.27, 4.21). CONCLUSIONS: Utilization of personal and employer-driven safety practices and increased coccidioidomycosis awareness among construction workers should be considered during the planning of any construction work in coccidioidomycosis-endemic regions to prevent occupational infections and outbreaks.

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.

Role of the Allergist-Immunologist and Upper Airway Allergy in Sleep-Disordered Breathing.

BACKGROUND: Sleep-disordered breathing in general and obstructive sleep apnea in particular are commonly encountered conditions in allergy practice. Physiologically, nasal (or nasopharyngeal) obstruction from rhinitis, nasal polyposis, or adenotonsillar hypertrophy are credible contributors to snoring and nocturnal respiratory obstructive events. Nevertheless, existing practice parameters largely relegate the role of the allergist to adjunctive treatment in cases of continuous positive airway pressure intolerance. OBJECTIVES: To survey active American Academy of Allergy, Asthma & Immunology members regarding their perceptions and practices concerning sleep-disordered breathing in adult and pediatric patients with rhinitis, and to review the medical literature concerning this connection to identify therapeutic implications and research gaps. METHODS: Members of the Work Group on Rhinitis and Sleep-disordered Breathing composed and distributed a Web-based clinically oriented survey to active American Academy of Allergy, Asthma & Immunology members in mid-2015. The group, in addition, conducted an English-language literature review using PubMed and other sources. RESULTS: Survey results were returned by 339 of 4881 active members (7%). More than two-third of respondents routinely asked about sleep problems, believed that sleep-disordered breathing was a problem for at least a "substantial minority" (10%-30%) of their adult patients, and believed that medical therapy for upper airway inflammatory conditions could potentially help ameliorate sleep-related complaints. Literature review supported the connection between high-grade nasal congestion/adenotonsillar hypertrophy and obstructive sleep apnea, and at least in the case of pediatric patients, supported the use of anti-inflammatory medication in the initial management of obstructive sleep apnea of mild-to-moderate severity. CONCLUSIONS: Clinical allergy practice and the medical literature support a proactive role for allergists in the diagnosis and management of sleep-disordered breathing.

Nonallergic Rhinitis: Environmental Determinants.

"Nonallergic rhinitis" (NAR) is defined by intermittent or persistent nasal symptoms without evidence of immunoglobulin E-mediated sensitization to relevant aeroallergens. The largest subgroup is idiopathic, and is characterized by nasal hyperreactivity to nonspecific environmental triggers, including temperature, humidity, and chemical exposures. As nonspecific nasal hyperreactivity is often found in the absence of mucosal inflammation, some clinicians refer to this condition as "nonallergic rhinopathy." Irritant rhinitis, can arise de novo after high-level and/or prolonged exposure to airborne irritant chemicals. We review the range of environmentally induced nonallergic nasal symptoms and signs, and explore issues of pathophysiology unique to environmental chemical exposures.

Coccidioidomycosis among Workers Constructing Solar Power Farms, California, USA, 2011-2014.

Coccidioidomycosis is associated with soil-disruptive work in Coccidioides-endemic areas of the southwestern United States. Among 3,572 workers constructing 2 solar power-generating facilities in San Luis Obispo County, California, USA, we identified 44 patients with symptom onset during October 2011-April 2014 (attack rate 1.2 cases/100 workers). Of these 44 patients, 20 resided in California outside San Luis Obispo County and 10 resided in another state; 9 were hospitalized (median 3 days), 34 missed work (median 22 days), and 2 had disseminated disease. Of the 25 patients who frequently performed soil-disruptive work, 6 reported frequent use of respiratory protection. As solar farm construction in Coccidioides-endemic areas increases, additional workers will probably be exposed and infected unless awareness is emphasized and effective exposure reduction measures implemented, including limiting dust generation and providing respiratory protection. Medical providers, including those in non-Coccidioides-endemic areas, should suspect coccidioidomycosis in workers with compatible illness and report cases to their local health department.

Occupational irritant and allergic rhinitis.

The upper airway (extending from the nares to larynx) fulfills essential physiologic functions, including sensation, air conditioning, filtration, and communication. As the portal of entry for the respiratory tract, the upper airway's sentinel function is performed by the olfactory and trigeminal nerves. Sensory (eye, nose and throat) irritation figures prominently in symptom reporting in so-called "problem buildings," as well as in industrial exposures to irritant gases, vapors, and smokes. Both irritants and allergens can alter function in the upper airway, leading to loss of air conditioning and filtering due to airflow obstruction and hypersecretion. Increasing evidence points to a "unified airway" model of pathogenesis (in which rhinitis may precede the development of asthma). The spectrum of occupational irritant- and allergen-related upper airway health effects-including sensory irritation, olfactory dysfunction, rhinitis, sinusitis, nasal septal perforation, and sinonasal cancer-is reviewed in this article.