Occupational rhinitis is a frequently underdiagnosed condition that can cause patient morbidity, potentially progress to asthma, and result in economic hardship for both the individual and the workforce. It is important to screen for work-related exposures and have knowledge of high molecular weight and low molecular weight agents in the workplace, as well as common occupational irritants. Having a methodical diagnostic approach, understanding primary, secondary, and tertiary prevention measures, recognizing comorbid disease and utilizing targeted management strategies will, in all likelihood, improve patient outcomes. Challenging cases may require co-management of Allergy with both Primary Care and Occupational Medicine.

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.

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.

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.

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.

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.

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 similar 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.

This case series analyzes characteristics of methylene chloride–related fatalities in the United States from 1980 to 2018.

The term occupational rhinitis (OR) refers to the inception of rhinitis induced by either immunologically mediated sensitization to a specific substance at the workplace (i.e. sensitizer-induced occupational rhinitis or allergic occupational rhinitis—hereafter referred to as OR) or by exposure to an inhaled irritant at work, which is termed irritant-induced occupational rhinitis. OR is characterized clinically by the development of nasal hypersensitivity to a specific occupational agent after an asymptomatic period of exposure, the so-called latency period, which is necessary to acquire immunological sensitization to the causal agent. The workplace agents capable of causing OR are the same as those identified as inducing sensitizer-induced OA, including high-molecular-weight (HMW) and low-molecular-weight (LMW) agents. In the case of irritant-induced OR, transient or persistent nasal symptoms may occur within a few hours after a single or repeated exposure to high concentrations of irritant compounds, such as chlorine, chlorine dioxide, sulfur dioxide, ozone, and hydrogen sulfide. By analogy with work-exacerbated asthma, work-exacerbated rhinitis has been defined as preexisting or concurrent (allergic or nonallergic) rhinitis that is worsened by workplace exposures, while the disease itself was not initiated by the work environment. There is a significant association between OR and OA in individual workers. OR is probably two to three times more frequent than OA. As for OA, the level of exposure to the sensitizing agent is the most important determinant of the development of IgE-mediated sensitization and OR due to HMW agents. Nasal provocation test is a useful test to confirm the diagnosis of OR. A diagnostic algorithm is proposed. Subjects with OR should be advised to diminish exposure to the causal agent to reduce the risk of developing OA.

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.

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.

This chapter is the first of two chapters demonstrating the wide variety of CFD studies in clinical applications presented from leading researchers in their respective fields. This chapter covers the latest research techniques and outcomes in airflow and conditioning in the nasal cavity; fluid and particle dynamics from sniffing; nasal obstruction and empty nose syndrome; nasal nitric oxide (nNO) dynamics and the ostiomeatal complex.

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.

Nasal mucociliary clearance is impaired in primary ciliary dyskinesia (PCD) and cystic fibrosis, as well as most inflammatory conditions of the nose, including allergic rhinitis, chronic rhinosinusitis, and chronic exposure to environmental irritants.1-8 Although no longer used as an initial screening test for PCD, the saccharin transit time (STT; the interval between instillation of a small grain of saccharin near the tip of an inferior turbinate and the subsequent subject report of a sweet taste on the tongue) may serve as a practical bedside assay for nasal mucociliary clearance in selected situations, albeit not without its technical challenges. Foremost among these are the physical form and quantity of crystalline saccharin, as well as the application device and procedure.9 We evaluated a novel variant testing technique, using a concentrated sodium saccharin solution as the stimulus and a flexible-shaft calcium alginate-tipped applicator to deliver the stimulus to the inferior turbinate. In addition to monitoring patient acceptability, we validated the measure by comparing results between individuals with self-reported allergic rhinitis and non-rhinitic controls. Research subjects were recruited via posters placed at a university research campus and a public health office complex. Non-smoking individuals aged 18 to 70 years, with no history of asthma, chronic cardiac or pulmonary conditions, angioedema or anaphylaxis, nor prior sinus surgery, were considered. Informed consent was obtained per institutional guidelines, and subjects were reimbursed for their time. After screening procedures (described in the next paragraph) we ultimately recruited 10 subjects total, 5 with and 5 without a self-reported history of allergic rhinitis, including 6 females and 4 males ranging in age from 21 to 53 years. Testing took place on 3 separate days—generally 1 week apart—in a temperature-regulated office environment (22°C ± 1.5°C). Subjects were asked to avoid eating, drinking (other than water), and engaging in vigorous exercise for the hour prior to each testing session. At the first

Question Is baseline rhinitis status (allergic, nonallergic, or none) associated with change in nasal congestion when continuous positive airway pressure (CPAP) is used? Findings In this cohort study of 102 participants with newly diagnosed obstructive sleep apnea, CPAP was associated with improved subjective nasal congestion on average, but less so in participants with baseline allergic rhinitis. Meaning Baseline allergic rhinitis may predict which patients are more vulnerable to potential congestive effects of CPAP. 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. This cohort study assesses whether continuous positive airway pressure (CPAP) therapy is associated with nasal congestion in patients with allergic rhinitis, nonallergic rhinitis, or no rhinitis.

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.

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.

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.