Protocol for the air purification for eosinophilic COPD study (APECS): a randomised controlled trial of home air filtration by HEPA.

INTRODUCTION: Exposure to particulate matter (PM) pollution has been associated with lower lung function in adults with chronic obstructive pulmonary disease (COPD). Patients with eosinophilic COPD have been found to have higher levels of airway inflammation, greater responsiveness to anti-inflammatory steroid inhalers and a greater lung function response to PM pollution exposure compared with those with lower eosinophil levels. This study will evaluate if reducing home PM exposure by high-efficiency particulate air (HEPA) air filtration improves respiratory health in eosinophilic COPD. METHODS AND ANALYSIS: The Air Purification for Eosinophilic COPD Study (APECS) is a double-blinded randomised placebo-controlled trial that will enrol 160 participants with eosinophilic COPD living in the area of Boston, Massachusetts. Real and sham air purifiers will be placed in the bedroom and living rooms of the participants in the intervention and control group, respectively, for 12 months. The primary trial outcome will be the change in forced expiratory volume in 1 s (FEV1). Lung function will be assessed twice preintervention and three times during the intervention phase (at 7 days, 6 months and 12 months postrandomisation). Secondary trial outcomes include changes in (1) health status by St. George's Respiratory Questionnaire; (2) respiratory symptoms by Breathlessness, Cough and Sputum Scale (BCSS); and (3) 6-Minute Walk Test (6MWT). Inflammatory mediators were measured in the nasal epithelial lining fluid (NELF). Indoor PM will be measured in the home for the week preceding each study visit. The data will be analysed to contrast changes in outcomes in the intervention and control groups using a repeated measures framework. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Institutional Review Board of Beth Israel Deaconess Medical Centre (protocol #2019P0001129). The results of the APECS trial will be presented at scientific conferences and published in peer-reviewed journals. TRIAL REGISTRATION: NCT04252235. Version: October 2023.

Age and Task Modulate Olfactory Sensitivity in the Florida Carpenter Ant Camponotus floridanus.

Age-related changes in behavior and sensory perception have been observed in a wide variety of animal species. In ants and other eusocial insects, workers often progress through an ordered sequence of olfactory-driven behavioral tasks. Notably, these behaviors are plastic, and workers adapt and rapidly switch tasks in response to changing environmental conditions. In the Florida carpenter ant, smaller minors typically perform most of the work needed to maintain the colony, while the larger majors are specialized for nest defense and rarely engage in these routine tasks. Here, we investigate the effects of age and task group on olfactory responses to a series of odorant blends in minor and major worker castes. Consistent with their respective roles within the colony, we observed significant age-associated shifts in the olfactory responses of minors as they transitioned between behavioral states, whereas the responses of majors remained consistently low regardless of age. Furthermore, we have identified a unitary compound, 3-methylindole, which elicited significantly higher responses and behavioral aversion in minor nurses than in similarly aged foragers suggesting that this compound may play an important role in brood care. Taken together, our results suggest that age- and task-associated shifts in olfactory physiology may play a critical role in the social organization of ant colonies.

Discrete roles of Ir76b ionotropic coreceptor impact olfaction, blood feeding, and mating in the malaria vector mosquito Anopheles coluzzii.

Anopheline mosquitoes rely on their highly sensitive chemosensory apparatus to detect diverse chemical stimuli that drive the host-seeking and blood-feeding behaviors required to vector pathogens for malaria and other diseases. This process incorporates a variety of chemosensory receptors and transduction pathways. We used advanced in vivo gene-editing and -labeling approaches to localize and functionally characterize the ionotropic coreceptor AcIr76b in the malaria mosquito Anopheles coluzzii, where it impacts both olfactory and gustatory systems. AcIr76b has a broad expression pattern in female adult antennal grooved pegs, coeloconic sensilla, and T1 and T2 sensilla on the labellum, stylets, and tarsi, as well as the larval sensory peg. AcIr76b is colocalized with the Orco odorant receptor (OR) coreceptor in a subset of cells across the female antennae and labella. In contrast to Orco and Ir8a, chemosensory coreceptors that appear essential for the activity of their respective sets of chemosensory neurons in mosquitoes, AcIr76b−/− mutants maintain wild-type peripheral responses to volatile amines on the adult palps, labellum, and larval sensory cone. Interestingly, AcIr76b−/− mutants display significantly increased responses to amines in antennal grooved peg sensilla, while coeloconic sensilla reveal significant deficits in responses to several acids and amines. Behaviorally, AcIr76b mutants manifest significantly female-specific insemination deficits, and although AcIr76b−/− mutant females can locate, alight on, and probe artificial blood hosts, they are incapable of blood feeding successfully. Taken together, our findings reveal a multidimensional functionality of Ir76b in anopheline olfactory and gustatory pathways that directly impacts the vectorial capacity of these mosquitoes.

Quantifying factors affecting contributions of roadway exhaust and non-exhaust emissions to ambient PM10-2.5 and PM2.5-0.2 particles.

Traffic-related particulate matter (PM) plays an important role in urban air pollution. However, sources of urban pollution are difficult to distinguish. This study utilises a mobile particle concentrator platform and statistical tools to investigate factors affecting roadway ambient coarse particle (PM10-2.5) and fine particle (PM2.5-0.2) concentrations in greater Boston, USA. Positive matrix factorization (PMF) identified six PM10-2.5 sources (exhaust, road salt, brake wear, regional pollution, road dust resuspension and tyre-road abrasion) and seven fine particle sources. The seven PM2.5-0.2 sources include the six PM10-2.5 sources and a source rich in Cr and Ni. Non- exhaust traffic-related sources together accounted for 65.6% and 29.1% of the PM10-2.5 and PM2.5-0.2 mass, respectively. While the respective contributions of exhaust sources were 10.4% and 20.7%. The biggest non-exhaust contributor in the PM10-2.5 was road dust resuspension, accounting for 29.6%, while for the PM2.5-0.2, the biggest non-exhaust source was road-tyre abrasion, accounting for 12.3%. We used stepwise general additive models (sGAMs) and found statistically significant (p < 0.05) effects of temperature, number of vehicles and rush hour periods on exhaust, brake wear, road dust resuspension and road-tyre abrasion with relative importance between 19.1 and 62.2%, 12.5-42.1% and 4.4-42.2% of the sGAM model's explained variability. Speed limit and road type were also important factors for exhaust, road-tyre and brake wear sources. Meteorological variables of wind speed and relative humidity were significantly associated with both coarse and fine road dust resuspension and had a combined relative importance of 38% and 48%. The quantifying results of the factors that influence traffic-related sources can offer key insights to policies aiming to improve near-road air quality.

Ammonium transporter AcAmt mutagenesis uncovers reproductive and physiological defects without impacting olfactory responses to ammonia in the malaria vector mosquito Anopheles coluzzii.

Anopheline mosquitoes are the sole vectors of malaria and rely on olfactory cues for host seeking in which ammonia derived from human sweat plays an essential role. To investigate the function of the Anopheles coluzzii ammonium transporter (AcAmt) in the mosquito olfactory system, we generated an AcAmt null mutant line using CRISPR/Cas9. AcAmt-/- mutants displayed a series of novel phenotypes compared with wild-type mosquitoes including significantly lower insemination rates during mating and increased mortality during eclosion. Furthermore, AcAmt-/- males showed significantly lower sugar consumption while AcAmt-/- females and pupae displayed significantly higher ammonia levels than their wild-type counterparts. Surprisingly, in contrast to previous studies in Drosophila that revealed that the mutation of the ammonium transporter (DmAmt) induces a dramatic reduction of ammonia responses in antennal coeloconic sensilla, no significant differences were observed across a range of peripheral sensory neuron responses to ammonia and other odorants between wild-type and AcAmt-/- females. These data support the existence in mosquitoes of novel compensatory ammonia-sensing mechanisms that are likely to have evolved as a result of the importance of ammonia in host-seeking and other behaviors.

Advances in the Study of Olfaction in Eusocial Ants.

Over the past decade, spurred in part by the sequencing of the first ant genomes, there have been major advances in the field of olfactory myrmecology. With the discovery of a significant expansion of the odorant receptor gene family, considerable efforts have been directed toward understanding the olfactory basis of complex social behaviors in ant colonies. Here, we review recent pivotal studies that have begun to reveal insights into the development of the olfactory system as well as how olfactory stimuli are peripherally and centrally encoded. Despite significant biological and technical impediments, substantial progress has been achieved in the application of gene editing and other molecular techniques that notably distinguish the complex olfactory system of ants from other well-studied insect model systems, such as the fruit fly. In doing so, we hope to draw attention not only to these studies but also to critical knowledge gaps that will serve as a compass for future research endeavors.

The Microbiome of Size-Fractionated Airborne Particles from the Sahara Region.

Diverse airborne microbes affect human health and biodiversity, and the Sahara region of West Africa is a globally important source region for atmospheric dust. We collected size-fractionated (>10, 10-2.5, 2.5-1.0, 1.0-0.5, and <0.5 µm) atmospheric particles in Mali, West Africa and conducted the first cultivation-independent study of airborne microbes in this region using 16S rRNA gene sequencing. Abundant and diverse microbes were detected in all particle size fractions at levels higher than those previously hypothesized for desert regions. Average daily abundance was 1.94 × 105 16S rRNA copies/m3. Daily patterns in abundance for particles <0.5 µm differed significantly from other size fractions likely because they form mainly in the atmosphere and have limited surface resuspension. Particles >10 µm contained the greatest fraction of daily abundance (51-62%) and had significantly greater diversity than smaller particles. Greater bacterial abundance of particles >2.5 µm that are bigger than the average bacterium suggests that most airborne bacteria are present as aggregates or attached to particles rather than as free-floating cells. Particles >10 µm have very short atmospheric lifetimes and thus tend to have more localized origins. We confirmed the presence of several potential pathogens using polymerase chain reaction that are candidates for viability and strain testing in future studies. These species were detected on all particle sizes tested, including particles <2.5 µm that are expected to undergo long-range transport. Overall, our results suggest that the composition and sources of airborne microbes can be better discriminated by collecting size-fractionated samples.

Odor coding of nestmate recognition in the eusocial ant Camponotus floridanus.

In eusocial ants, aggressive behaviors require the ability to discriminate between chemical signatures such as cuticular hydrocarbons that distinguish nestmate friends from non-nestmate foes. It has been suggested that a mismatch between a chemical signature (label) and the internal, neuronal representation of the colony odor (template) leads to aggression between non-nestmates. Moreover, a definitive demonstration that odorant receptors are responsible for the processing of the chemical signals that regulate nestmate recognition has thus far been lacking. To address these issues, we have developed an aggression-based bioassay incorporating highly selective modulators that target odorant receptor functionality to characterize their role in nestmate recognition in the formicine ant Camponotus floridanus Electrophysiological studies were used to show that exposure to either a volatilized antagonist or an agonist eliminated or dramatically altered signaling, respectively. Administration of these compounds to adult workers significantly reduced aggression between non-nestmates without altering aggression levels between nestmates. These studies provide direct evidence that odorant receptors are indeed necessary and sufficient for mediating aggression towards non-nestmates. Furthermore, our observations support a hypothesis in which rejection of non-nestmates depends on the precise decoding of chemical signatures present on non-nestmates as opposed to the absence of any information or the active acceptance of familiar signatures.

Characterization of Chemosensory Responses on the Labellum of the Malaria Vector Mosquito, Anopheles coluzzii.

Anopheles gambiae coluzzii (An. coluzzii) uses olfaction to modulate a range of critical behaviors that are essential for survival and reproduction; most notably, host preference and selection underlie its vectorial capacity for human malaria. As is the case for all mosquitoes, An. coluzzii has three specialized peripheral olfactory appendages-the antennae, maxillary palps and labella-which are used to detect and orient in response to a large variety of olfactory cues. Of these, neither the molecular nor the physiological significance of the labellum have been thoroughly characterized despite suggestions that labial-derived odorant reception is critical for close-range host attraction. Here we report global chemoreceptor transcriptome profiles together with a systematic electrophysiological analysis of labial T2 sensilla, and associated behavioral responses of female An. coluzzii. Single sensillum recordings of the T2 sensilla revealed robust responses to odorants previously associated with human sweat and oviposition sites and identified a 10-component blend that elicited attraction in a dual-choice landing bioassay designed to mimic host seeking in which non-blood fed females were significantly more attracted to the labial-responsive odorant blend as compared to gravid females. Taken together, these data suggest that, in An. coluzzii, olfactory responses derived from the labellum contribute to host-seeking.

Functional characterization of odorant receptors in the ponerine ant, Harpegnathos saltator.

Animals use a variety of sensory modalities-including visual, acoustic, and chemical-to sense their environment and interact with both conspecifics and other species. Such communication is especially critical in eusocial insects such as honey bees and ants, where cooperation is critical for survival and reproductive success. Various classes of chemoreceptors have been hypothesized to play essential roles in the origin and evolution of eusociality in ants, through their functional roles in pheromone detection that characterizes reproductive status and colony membership. To better understand the molecular mechanisms by which chemoreceptors regulate social behaviors, we investigated the roles of a critical class of chemoreceptors, the odorant receptors (ORs), from the ponerine ant Harpegnathos saltator in detecting cuticular hydrocarbon pheromones. In light of the massive OR expansion in ants (∼400 genes per species), a representative survey based on phylogenetic and transcriptomic criteria was carried out across discrete odorant receptor subfamilies. Responses to several classes of semiochemicals are described, including cuticular hydrocarbons and mandibular gland components that act as H. saltator pheromones, and a range of more traditional general odorants. When viewed through the prism of caste-specific OR enrichment and distinctive OR subfamily odorant response profiles, our findings suggest that whereas individual HsOrs appear to be narrowly tuned, there is no apparent segregation of tuning responses within any discrete HsOr subfamily. Instead, the HsOR gene family as a whole responds to a broad array of compounds, including both cuticular hydrocarbons and general odorants that are likely to mediate distinct behaviors.

The School Inner-City Asthma Intervention Study: Design, rationale, methods, and lessons learned.

Asthma is the most common chronic disease of childhood in the United States, causes significant morbidity, particularly in the inner-city, and accounts for billions of dollars in health care utilization. Home environments are established sources of exposure that exacerbate symptoms and home-based interventions are effective. However, elementary school children spend 7 to 12h a day in school, primarily in one classroom. From the observational School Inner-City Asthma Study we learned that student classroom-specific exposures are associated with worsening asthma symptoms and decline in lung function. We now embark on a randomized, blinded, sham-controlled school environmental intervention trial, built on our extensively established school/community partnerships, to determine the efficacy of a school-based intervention to improve asthma control. This factorial school/classroom based environmental intervention will plan to enroll 300 students with asthma from multiple classrooms in 40 northeastern inner-city elementary schools. Schools will be randomized to receive either integrated pest management versus control and classrooms within these schools to receive either air purifiers or sham control. The primary outcome is asthma symptoms during the school year. This study is an unprecedented opportunity to test whether a community of children can benefit from school or classroom environmental interventions. If effective, this will have great impact as an efficient, cost-effective intervention for inner city children with asthma and may have broad public policy implications.

Development and Performance Evaluation of an Exhaled-Breath Bioaerosol Collector for Influenza Virus.

The importance of the aerosol mode for transmission of influenza is unknown. Understanding the role of aerosols is essential to developing public health interventions such as the use of surgical masks as a source control to prevent the release of infectious aerosols. Little information is available on the number and size of particles generated by infected persons, which is partly due to the limitations of conventional air samplers, which do not efficiently capture fine particles or maintain microorganism viability. We designed and built a new sampler, called the G-II, that collects exhaled breath particles that can be used in infectivity analyses. The G-II allows test subjects to perform various respiratory maneuvers (i.e. tidal breathing, coughing, and talking) and allows subjects to wear a mask or respirator during testing. A conventional slit impactor collects particles > 5.0 µm. Condensation of water vapor is used to grow remaining particles, including fine particles, to a size large enough to be efficiently collected by a 1.0 µm slit impactor and be deposited into a buffer-containing collector. We evaluated the G-II for fine particle collection efficiency with inert particle aerosols and evaluated infective virus collection using influenza A virus aerosols. Testing results showed greater than 85% collection efficiency for particles greater than 50nm and influenza virus collection comparable with a reference SKC BioSampler®. The new design will enable determination of exhaled infectious virus generation rate and evaluate control strategies such as wearing a surgical type mask to prevent the release of viruses from infected persons.

Development and evaluation of a countercurrent parallel-plate membrane diffusion denuder for the removal of gas-phase compounds from vehicular emissions.

Diffusion denuders have been commonly used to remove trace gases from an aerosol (mixture of gases and particles), while allowing the particles to remain suspended in air. We present the design and evaluation of a high-flow (16.7 L min⁻¹) countercurrent parallel-plate membrane diffusion denuder that has high removal efficiencies for both non-reactive gases such as carbon monoxide (89%), as well as volatile organic compounds (80-85%) from an automobile exhaust. Particle losses were approximately 15% for particles around 100 nm in diameter. This denuder is suitable for toxicological tests involving both human and animal exposures to combustion aerosols. The denuder may also be used for other applications, for example, to reduce the effect of gas-phase sampling artifacts on particle composition.

Laboratory evaluation of a prototype photochemical chamber designed to investigate the health effects of fresh and aged vehicular exhaust emissions.

Laboratory experiments simulating atmospheric aging of motor vehicle exhaust emissions were conducted using a single vehicle and a photochemical chamber. A compact automobile was used as a source of emissions. The vehicle exhaust was diluted with ambient air to achieve carbon monoxide (CO) concentrations similar to those observed in an urban highway tunnel. With the car engine idling, it is expected that the CO concentration is a reasonable surrogate for volatile organic compounds (VOCs) emissions. Varying the amount of dilution of the exhaust gas to produce different CO concentrations, allowed adjustment of the concentrations of VOCs in the chamber to optimize production of secondary organic aerosol (SOA) needed for animal toxicological exposures. Photochemical reactions in the chamber resulted in nitric oxide (NO) depletion, nitrogen dioxide (NO2) formation, ozone (O3) accumulation, and SOA formation. A stable SOA concentration of approximately 40 µg m⁻³ at a chamber mean residence time of 30 min was achieved. This relatively short mean residence time provided adequate chamber flow output for both particle characterization and animal exposures. The chamber was operated as a continuous flow reactor for animal toxicological tests. SOA mass generated from the car exhaust diluted with ambient air was almost entirely in the ultrafine mode. Chamber performance was improved by using different types of seed aerosol to provide a surface for condensation of semivolatile reaction products, thus increasing the yield of SOA. Toxicological studies using Sprague-Dawley rats found significant increases of in vivo chemiluminescence in lungs following exposure to SOA.

Aged particles derived from emissions of coal-fired power plants: the TERESA field results.

The Toxicological Evaluation of Realistic Emissions Source Aerosols (TERESA) study was carried out at three US coal-fired power plants to investigate the potential toxicological effects of primary and photochemically aged (secondary) particles using in situ stack emissions. The exposure system designed successfully simulated chemical reactions that power plant emissions undergo in a plume during transport from the stack to receptor areas (e.g., urban areas). Test atmospheres developed for toxicological experiments included scenarios to simulate a sequence of atmospheric reactions that can occur in a plume: (1) primary emissions only; (2) H(2)SO(4) aerosol from oxidation of SO(2); (3) H(2)SO(4) aerosol neutralized by gas-phase NH(3); (4) neutralized H(2)SO(4) with secondary organic aerosol (SOA) formed by the reaction of α-pinene with O(3); and (5) three control scenarios excluding primary particles. The aged particle mass concentrations varied significantly from 43.8 to 257.1 µg/m(3) with respect to scenario and power plant. The highest was found when oxidized aerosols were neutralized by gas-phase NH(3) with added SOA. The mass concentration depended primarily on the ratio of SO(2) to NO(x) (particularly NO) emissions, which was determined mainly by coal composition and emissions controls. Particulate sulfate (H(2)SO(4) + neutralized sulfate) and organic carbon (OC) were major components of the aged particles with added SOA, whereas trace elements were present at very low concentrations. Physical and chemical properties of aged particles appear to be influenced by coal type, emissions controls and the particular atmospheric scenarios employed.

Development and evaluation of a photochemical chamber to examine the toxicity of coal-fired power plant emissions.

When investigating the toxicity of individual particle sources, it is important to consider the contribution of both primary and secondary particles. In this article, we present the design of a new photochemical chamber that can be used to form secondary sulfuric acid particles from diluted coal-fired power plant emissions. The chamber is a relatively small, well-mixed flow reactor that can fit in a mobile reaction laboratory. It produces high concentrations of hydroxyl radical (OH) from the photolysis of ozone (O3) in the presence of water vapor. Two chambers were built and tested. A pilot chamber was tested in the laboratory, using mixtures of NO and SO2 in air, at concentrations that are approximately 100 times lower than those in power plant stack emissions. This chamber was able to oxidize about 20% of the SO2, thereby producing 1350 microg m(-3) of H2SO4 particles. Further tests showed that increasing O3 concentrations and residence time increased the H2SO4 production. A field chamber was built subsequently and used in a toxicological study. Diluted coal-fired power plant emissions were introduced in the chamber. Over 19 days of exposure, the chamber, on average, converted 17% of the supplied SO2 emissions and produced an average of 350 microg m(-3) of H2SO4 particles. Particle losses were determined for the pilot chamber, using artificial particles whose size ranged from 50 to 1000 nm. The determined losses ranged from 21 to 42%, with no trend between the amount of particle loss and particle size. Losses for the field chamber, estimated using model calculations, were found to be similar to those of the pilot chamber.

Development of an exposure system for the toxicological evaluation of particles derived from coal-fired power plants.

To investigate the toxicity of particles originating from coal-fired power plants it is necessary to consider the effects of both primary particles and secondary components formed in the air through atmospheric reactions. This report describes a new exposure system that can be used to expose animals to both directly emitted particles and to secondary particles. The system consists of three main components. The first is a sampling system to continuously collect and dilute power plant stack emissions. The second is a reaction laboratory that contains reaction chambers to simulate atmospheric reactions. The following atmospheric reactions were simulated: (1) the oxidation of sulfur dioxide to form sulfuric acid, (2) the neutralization of sulfuric acid by ammonia, and (3) the reaction of alpha-pinene with ozone to form secondary organic aerosol. Using these chambers with the diluted emissions, different typical atmospheric scenarios can be simulated. The final component is a mobile toxicology laboratory where animals are exposed to the resulting test aerosols. We report here the characteristics of the test aerosol exposures obtained at a coal-fired electric power plant. Particle exposures were characterized for concentrations of mass, elements, elemental carbon, organic species, inorganic ions, strong acidity, particle number, and size distributions. Mass concentrations ranged from a few micrograms per cubic meter for a scenario of primary emissions only, to about 250 microg m(-3) for the most complex scenario. We show that the different scenarios produced a large variation in the composition of the test aerosol, thus potentially changing the toxicity of the emissions.

A counter-current parallel-plate membrane denuder for the non-specific removal of trace gases.

In this paper we present a counter-current parallel-plate membrane diffusion denuder for the non-specific removal of trace gases from an air flow. In this design, gaseous pollutants are removed by diffusing from a sample channel to two purge channels by crossing microporous membranes. In the laboratory, at a sample flow rate of 5 L/min and purge flow rates of 5 L/min each, gas removal efficiencies ranged from 84% for CO to 72% for SF6. Removal efficiencies increased with lower sample flow rate, a higher sample to purge flow rate ratio, a longer channel length, and using molecules with higher diffusion coefficient. Removal efficiencies were, however, not affected by the sample channel height. In addition, gas penetration was exponentially associated with the product of channel length, diffusion coefficient, and the inverse of sample flow rate. Particle losses were significant (10-25% losses) only for particles smaller than 50 nm. In a field evaluation, the denuder's performance was tested with an aerosol produced in a photochemical chamber. The denuder's performance was similar to that observed in the laboratory and was stable over time. Finally, the denuder was tested with a semivolatile organic aerosol. Particle mass losses due to volatilization were about 30%.