Janneane F. Gent

Evaluation of olfactory dysfunction in the connecticut chemosensory clinical research center

The olfactory test administered to patients at the Connecticut Chemosensory Clinical Research Center combines stability of outcome with sensitivity to variables known to affect olfaction (age, sex). The test, which pairs an odor threshold component with an odor identification component, readily resolves differences in function between patients and controls. It reveals differences in the distribution of functioning for various probable causes (nasal/sinus disease, postupper respiratory infection, and head trauma), proves sensitive to improvements in function caused by therapeutic intervention (ethmoidectomy, steroid administration for nasal/sinus disease), and correlates with objective signs of nasal/sinus disease (visual exam, x‐ray). The two components of the test agree well, though the odor identification component seems somewhat more sensitive than the threshold component as currently designed.

Clinical evaluation of olfaction

An odor identification test and an odor threshold test offered satisfactory quantitative information on olfactory function in patients with chemosensory complaints. The threshold test used various concentrations of butanol presented in an ascending sequence. On each trial, the participant had to choose between stimulus and blank (two-alternative forced-choice procedure). The identification test used common odorous items (e.g., baby powder and ground coffee) and pungent items (e.g., ammonia) to test trigeminal function. A list of odor names and use of corrective feedback during testing overcame word-finding difficulty in odor identification. Each test readily distinguished between patients and control subjects. At present, a score that reflects the combined outcome of the tests is used to indicate five categories of functioning: normal osmesis, mild hyposmia, moderate hyposmia, severe hyposmia, and anosmia.

Microbial interactions during upper respiratory tract infections.

Competitive interactions between bacteria differ by number and species present; thus, vaccination and treatment strategies may alter nasopharyngeal flora and disease susceptibility.

Prenatal Exposure to Fine Particulate Matter and Birth Weight: Variations by Particulate Constituents and Sources

Background: Exposure to fine particles (PM2.5) during pregnancy has been linked to lower birth weight; however, the chemical composition of PM2.5 varies widely. The health effects of PM2.5 constituents are unknown. Methods: We investigated whether PM2.5 mass, constituents, and sources are associated with birth weight for term births. PM2.5 filters collected in 3 Connecticut counties and 1 Massachusetts county from August 2000 through February 2004 were analyzed for more than 50 elements. Source apportionment was used to estimate daily contributions of PM2.5 sources, including traffic, road dust/crustal, oil combustion, salt, and regional (sulfur) sources. Gestational and trimester exposure to PM2.5 mass, constituents, and source contributions were examined in relation to birth weight and risk of small-at-term birth (term birth <2500 g) for 76,788 infants. Results: Road dust and related constituents such as silicon and aluminum were associated with lower birth weight, as were the motor-vehicle-related species such as elemental carbon and zinc, and the oil-combustion-associated elements vanadium and nickel. An interquartile range increase in exposure was associated with low birthweight for zinc (12% increase in risk), elemental carbon (13%), silicon (10%), aluminum (11%), vanadium (8%), and nickel (11%). Analysis by trimester showed effects of third-trimester exposure to elemental carbon, nickel, vanadium, and oil-combustion PM2.5. Conclusions: Exposures of pregnant women to higher levels of certain PM2.5 chemical constituents originating from specific sources are associated with lower birth weight.

Symptoms and Medication Use in Children with Asthma and Traffic-Related Sources of Fine Particle Pollution

Background Exposure to ambient fine particles [particulate matter ≤ 2.5 μm diameter (PM2.5)] is a potential factor in the exacerbation of asthma. National air quality particle standards consider total mass, not composition or sources, and may not protect against health impacts related to specific components. Objective We examined associations between daily exposure to fine particle components and sources, and symptoms and medication use in children with asthma. Methods Children with asthma (n = 149) 4–12 years of age were enrolled in a year-long study. We analyzed particle samples for trace elements (X-ray fluorescence) and elemental carbon (light reflectance). Using factor analysis/source apportionment, we identified particle sources (e.g., motor vehicle emissions) and quantified daily contributions. Symptoms and medication use were recorded on study diaries. Repeated measures logistic regression models examined associations between health outcomes and particle exposures as elemental concentrations and source contributions. Results More than half of mean PM2.5 was attributed to traffic-related sources motor vehicles (42%) and road dust (12%). Increased likelihood of symptoms and inhaler use was largest for 3-day averaged exposures to traffic-related sources or their elemental constituents and ranged from a 10% increased likelihood of wheeze for each 5-μg/m3 increase in particles from motor vehicles to a 28% increased likelihood of shortness of breath for increases in road dust. Neither the other sources identified nor PM2.5 alone was associated with increased health outcome risks. Conclusions Linking respiratory health effects to specific particle pollution composition or sources is critical to efforts to protect public health. We associated increased risk of symptoms and inhaler use in children with asthma with exposure to traffic-related fine particles.

Microbial Communities of the Upper Respiratory Tract and Otitis Media in Children

ABSTRACT Streptococcus pneumoniae asymptomatically colonizes the upper respiratory tract of children and is a frequent cause of otitis media. Patterns of microbial colonization likely influence S. pneumoniae colonization and otitis media susceptibility. This study compared microbial communities in children with and without otitis media. Nasal swabs and clinical and demographic data were collected in a cross-sectional study of Philadelphia, PA, children (6 to 78 months) (n = 108) during the 2008-2009 winter respiratory virus season. Swabs were cultured for S. pneumoniae. DNA was extracted from the swabs; 16S rRNA gene hypervariable regions (V1 and V2) were PCR amplified and sequenced by Roche/454 Life Sciences pyrosequencing. Microbial communities were described using the Shannon diversity and evenness indices. Principal component analysis (PCA) was used to group microbial community taxa into four factors representing correlated taxa. Of 108 children, 47 (44%) were colonized by S. pneumoniae, and 25 (23%) were diagnosed with otitis media. Microbial communities with S. pneumoniae were significantly less diverse and less even. Two PCA factors were associated with a decreased risk of pneumococcal colonization and otitis media, as follows: one factor included potentially protective flora (Corynebacterium and Dolosigranulum), and the other factor included Propionibacterium, Lactococcus, and Staphylococcus. The remaining two PCA factors were associated with an increased risk of otitis media. One factor included Haemophilus, and the final factor included Actinomyces, Rothia, Neisseria, and Veillonella. Generally, these taxa are not considered otitis media pathogens but may be important in the causal pathway. Increased understanding of upper respiratory tract microbial communities will contribute to the development of otitis media treatment and prevention strategies. IMPORTANCE Otitis media (middle ear infection) is the most common reason for pediatric sick visits in the United States. Streptococcus pneumoniae is a leading otitis media pathogen. S. pneumoniae must colonize the upper respiratory tract and compete with a complex community of nonpathogenic bacteria before infecting the middle ear. We compared microbial communities in the upper respiratory tract of children who had otitis media and those who did not. Members of the normal flora, i.e., Corynebacterium and Dolosigranulum, were protective for S. pneumoniae colonization and otitis media. As expected, the genera Haemophilus was associated with otitis media. Surprisingly, Actinomyces, Rothia, Neisseria, and Veillonella were associated with an increased risk of otitis media. These bacteria are not otitis media pathogens but may be associated with antibiotic use or involved in the causal pathway to disease. Increased understanding of upper respiratory tract microbial communities will lead to new ways to prevent middle ear infections, including probiotics. Otitis media (middle ear infection) is the most common reason for pediatric sick visits in the United States. Streptococcus pneumoniae is a leading otitis media pathogen. S. pneumoniae must colonize the upper respiratory tract and compete with a complex community of nonpathogenic bacteria before infecting the middle ear. We compared microbial communities in the upper respiratory tract of children who had otitis media and those who did not. Members of the normal flora, i.e., Corynebacterium and Dolosigranulum, were protective for S. pneumoniae colonization and otitis media. As expected, the genera Haemophilus was associated with otitis media. Surprisingly, Actinomyces, Rothia, Neisseria, and Veillonella were associated with an increased risk of otitis media. These bacteria are not otitis media pathogens but may be associated with antibiotic use or involved in the causal pathway to disease. Increased understanding of upper respiratory tract microbial communities will lead to new ways to prevent middle ear infections, including probiotics.

Viral-Bacterial Interactions and Risk of Acute Otitis Media Complicating Upper Respiratory Tract Infection

ABSTRACT Acute otitis media (AOM) is a common complication of upper respiratory tract infection whose pathogenesis involves both viruses and bacteria. We examined risks of acute otitis media associated with specific combinations of respiratory viruses and acute otitis media bacterial pathogens. Data were from a prospective study of children ages 6 to 36 months and included viral and bacterial culture and quantitative PCR for respiratory syncytial virus (RSV), human bocavirus, and human metapneumovirus. Repeated-measure logistic regression was used to assess the relationship between specific viruses, bacteria, and the risk of acute otitis media complicating upper respiratory tract infection. In unadjusted analyses of data from 194 children, adenovirus, bocavirus, Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis were significantly associated with AOM (P < 0.05 by χ2 test). Children with high respiratory syncytial virus loads (≥3.16 × 107 copies/ml) experienced increased acute otitis media risk. Higher viral loads of bocavirus and metapneumovirus were not significantly associated with acute otitis media. In adjusted models controlling for the presence of key viruses, bacteria, and acute otitis media risk factors, acute otitis media risk was independently associated with high RSV viral load with Streptococcus pneumoniae (odds ratio [OR], 4.40; 95% confidence interval [CI], 1.90 and 10.19) and Haemophilus influenzae (OR, 2.04; 95% CI, 1.38 and 3.02). The risk was higher for the presence of bocavirus and H. influenzae together (OR, 3.61; 95% CI, 1.90 and 6.86). Acute otitis media risk differs by the specific viruses and bacteria involved. Acute otitis media prevention efforts should consider methods for reducing infections caused by respiratory syncytial virus, bocavirus, and adenovirus in addition to acute otitis media bacterial pathogens.

Associations of PM2.5 Constituents and Sources with Hospital Admissions: Analysis of Four Counties in Connecticut and Massachusetts (USA) for Persons ≥ 65 Years of Age

Background: Epidemiological studies have demonstrated associations between short-term exposure to PM2.5 and hospital admissions. The chemical composition of particles varies across locations and time periods. Identifying the most harmful constituents and sources is an important health and regulatory concern. Objectives: We examined pollutant sources for associations with risk of hospital admissions for cardiovascular and respiratory causes. Methods: We obtained PM2.5 filter samples for four counties in Connecticut and Massachusetts and analyzed them for PM2.5 elements. Source apportionment was used to estimate daily PM2.5 contributions from sources (traffic, road dust, oil combustion, and sea salt as well as a regional source representing coal combustion and other sources). Associations between daily PM2.5 constituents and sources and risk of cardiovascular and respiratory hospitalizations for the Medicare population (> 333,000 persons ≥ 65 years of age) were estimated with time-series analyses (August 2000–February 2004). Results: PM2.5 total mass and PM2.5 road dust contribution were associated with cardiovascular hospitalizations, as were the PM2.5 constituents calcium, black carbon, vanadium, and zinc. For respiratory hospitalizations, associations were observed with PM2.5 road dust, and sea salt as well as aluminum, calcium, chlorine, black carbon, nickel, silicon, titanium, and vanadium. Effect estimates were generally robust to adjustment by co-pollutants of other constituents. An interquartile range increase in same-day PM2.5 road dust (1.71 μg/m3) was associated with a 2.11% (95% CI: 1.09, 3.15%) and 3.47% (95% CI: 2.03, 4.94%) increase in cardiovascular and respiratory admissions, respectively. Conclusions: Our results suggest some particle sources and constituents are more harmful than others and that in this Connecticut/Massachusetts region the most harmful particles include black carbon, calcium, and road dust PM2.5. Citation: Bell ML, Ebisu K, Leaderer BP, Gent JF, Lee HJ, Koutrakis P, Wang Y, Dominici F, Peng RD. 2014. Associations of PM2.5 constituents and sources with hospital admissions: analysis of four counties in Connecticut and Massachusetts (USA) for persons ≥ 65 years of age. Environ Health Perspect 122:138–144; http://dx.doi.org/10.1289/ehp.1306656

Upper respiratory tract microbial communities, acute otitis media pathogens and antibiotic use in healthy and sick children

ABSTRACT The composition of the upper respiratory tract microbial community may influence the risk for colonization by the acute otitis media (AOM) pathogens Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. We used culture-independent methods to describe upper respiratory tract microbial communities in healthy children and children with upper respiratory tract infection with and without concurrent AOM. Nasal swabs and data were collected in a cross-sectional study of 240 children between 6 months and 3 years of age. Swabs were cultured for S. pneumoniae, and real-time PCR was used to identify S. pneumoniae, H. influenzae, and M. catarrhalis. The V1-V2 16S rRNA gene regions were sequenced using 454 pyrosequencing. Microbial communities were described using a taxon-based approach. Colonization by S. pneumoniae, H. influenzae, and M. catarrhalis was associated with lower levels of diversity in upper respiratory tract flora. We identified commensal taxa that were negatively associated with colonization by each AOM bacterial pathogen and with AOM. The balance of these relationships differed according to the colonizing AOM pathogen and history of antibiotic use. Children with antibiotic use in the past 6 months and a greater abundance of taxa, including Lactococcus and Propionibacterium, were less likely to have AOM than healthy children (odds ratio [OR], 0.46; 95% confidence interval [CI], 0.25 to 0.85). Children with no antibiotic use in the past 6 months, a low abundance of Streptococcus and Haemophilus, and a high abundance of Corynebacterium and Dolosigranulum were less likely to have AOM (OR, 0.51; 95% CI, 0.31 to 0.83). An increased understanding of polymicrobial interactions will facilitate the development of effective AOM prevention strategies.

Association of pediatric asthma severity with exposure to common household dust allergens.

BACKGROUND Reducing exposure to household dust inhalant allergens has been proposed as one strategy to reduce asthma. OBJECTIVE To examine the dose-response relationships and health impact of five common household dust allergens on disease severity, quantified using both symptom frequency and medication use, in atopic and non-atopic asthmatic children. METHODS Asthmatic children (N=300) aged 4-12 years were followed for 1 year. Household dust samples from two indoor locations were analyzed for allergens including dust mite (Der p 1, Der f 1), cat (Fel d 1), dog (Can f 1), cockroach (Bla g 1). Daily symptoms and medication use were collected in monthly telephone interviews. Annual disease severity was examined in models including allergens, specific IgE sensitivity and adjusted for age, gender, atopy, ethnicity, and mothers education. RESULTS Der p 1 house dust mite allergen concentration of 2.0 microg/g or more from the main room and the childs bed was related to increased asthma severity independent of allergic status (respectively, OR 2.93, 95% CI 1.37, 6.30 for 2.0-10.0 microg/g and OR 2.55 95% CI 1.13, 5.73 for 10.0 microg/g). Higher pet allergen levels were associated with greater asthma severity, but only for those sensitized (cat OR 2.41 95% CI 1.19, 4.89; dog OR 2.06 95% CI 1.01, 4.22). CONCLUSION Higher levels of Der p 1 and pet allergens were associated with asthma severity, but Der p 1 remained an independent risk factor after accounting for pet allergens and regardless of Der p 1 specific IgE status.