Childhood asthma and household exposures to nitrogen dioxide and fine particles: a triple-crossover randomized intervention trial.

OBJECTIVE: Triple-crossover randomized controlled intervention trial to test whether reduced exposure to household NO2 or fine particles results in reduced symptoms among children with persistent asthma. METHODS: Children (n = 126) aged 5-11 years with persistent asthma living in homes with gas stoves and levels of NO2 15 ppb or greater recruited in Connecticut and Massachusetts (2015-2019) participated in an intervention involving three air cleaners configured for: (1) NO2 reduction: sham particle filtration and real NO2 scrubbing; (2) particle filtration: HEPA filter and sham NO2 scrubbing; (3) control: sham particle filtration and sham NO2 scrubbing. Air cleaners were randomly assigned for 5-week treatment periods using a three-arm crossover design. Outcome was number of asthma symptom-days during final 14 days of treatment. Treatment effects were assessed using repeated measures, linear mixed models. RESULTS: Measured NO2 was lower (by 4 ppb, p < .0001) for NO2-reducing compared to control or particle-reducing treatments. NO2-reducing treatment did not reduce asthma morbidity compared to control. In analysis controlling for measured NO2, there were 1.8 (95% CI -0.3 to 3.9, p = .10) fewer symptom days out of 14 in the particle-reducing treatment compared to control. CONCLUSIONS: It remains unknown if using an air cleaner alone can achieve levels of NO2 reduction large enough to observe reductions in asthma symptoms. We observed that in small, urban homes with gas stoves, modest reductions in asthma symptoms occurred using air cleaners that remove fine particles. An intervention targeting exposures to both NO2 and fine particles is complicated and further research is warranted. REGISTRATION NUMBER: NCT02258893.

Haemophilus influenzae genome evolution during persistence in the human airways in chronic obstructive pulmonary disease.

Nontypeable Haemophilus influenzae (NTHi) exclusively colonize and infect humans and are critical to the pathogenesis of chronic obstructive pulmonary disease (COPD). In vitro and animal models do not accurately capture the complex environments encountered by NTHi during human infection. We conducted whole-genome sequencing of 269 longitudinally collected cleared and persistent NTHi from a 15-y prospective study of adults with COPD. Genome sequences were used to elucidate the phylogeny of NTHi isolates, identify genomic changes that occur with persistence in the human airways, and evaluate the effect of selective pressure on 12 candidate vaccine antigens. Strains persisted in individuals with COPD for as long as 1,422 d. Slipped-strand mispairing, mediated by changes in simple sequence repeats in multiple genes during persistence, regulates expression of critical virulence functions, including adherence, nutrient uptake, and modification of surface molecules, and is a major mechanism for survival in the hostile environment of the human airways. A subset of strains underwent a large 400-kb inversion during persistence. NTHi does not undergo significant gene gain or loss during persistence, in contrast to other persistent respiratory tract pathogens. Amino acid sequence changes occurred in 8 of 12 candidate vaccine antigens during persistence, an observation with important implications for vaccine development. These results indicate that NTHi alters its genome during persistence by regulation of critical virulence functions primarily by slipped-strand mispairing, advancing our understanding of how a bacterial pathogen that plays a critical role in COPD adapts to survival in the human respiratory tract.

Gastrointestinal Microbiota Disruption and Risk of Colonization With Carbapenem-resistant Pseudomonas aeruginosa in Intensive Care Unit Patients.

BACKGROUND: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) colonizes the gastrointestinal tract of intensive care unit (ICU) patients, and CRPA colonization puts patients at increased risk of CRPA infection. Prior studies have not examined relationships between the microbiota, medications, and CRPA colonization acquisition. METHODS: Data and perirectal swabs were obtained from a cohort of ICU patients at the University of Maryland Medical Center. Patients (N = 109) were classified into 3 groups by CRPA colonization-acquisition status and antimicrobial exposure. We conducted 16S ribosomal RNA gene sequencing of an ICU admission swab and ≥1 additional swab and evaluated associations between patient characteristics, medications, the gastrointestinal microbiota, and CRPA colonization acquisition. RESULTS: ICU patients had low levels of diversity and high relative abundances of pathobionts. Piperacillin-tazobactam was prescribed more frequently to patients with CRPA colonization acquisition than those without. Piperacillin-tazobactam was associated with low abundance of potentially protective taxa (eg, Lactobacillus and Clostridiales) and increased risk of Enterococcus domination (odds ratio [OR], 5.50; 95% confidence interval [CI], 2.03-14.92). Opioids were associated with dysbiosis in patients who did not receive antibiotics; potentially protective Blautia and Lactobacillus were higher in patients who did not receive opioids. Several correlated taxa, identified at ICU admission, were associated with lower risk of CRPA colonization acquisition (OR, 0.58; 95% CI, .38-.87). CONCLUSIONS: Antibiotics differed in their impact on the microbiota, with piperacillin-tazobactam being particularly damaging. Certain bacterial taxa (eg, Clostridiales) were negatively associated with CRPA colonization acquisition. These taxa may be markers of risk for CRPA colonization acquisition and/or serve a protective role.

Indoor microbial communities: Influence on asthma severity in atopic and nonatopic children.

BACKGROUND: Allergic and nonallergic asthma severity in children can be affected by microbial exposures. OBJECTIVE: We sought to examine associations between exposures to household microbes and childhood asthma severity stratified by atopic status. METHODS: Participants (n = 196) were selected from a cohort of asthmatic children in Connecticut and Massachusetts. Children were grouped according to asthma severity (mild with no or minimal symptoms and medication or moderate to severe persistent) and atopic status (determined by serum IgE levels). Microbial community structure and concentrations in house dust were determined by using next-generation DNA sequencing and quantitative PCR. Logistic regression was used to explore associations between asthma severity and exposure metrics, including richness, taxa identification and quantification, community composition, and concentration of total fungi and bacteria. RESULTS: Among all children, increased asthma severity was significantly associated with an increased concentration of summed allergenic fungal species, high total fungal concentrations, and high bacterial richness by using logistic regression in addition to microbial community composition by using the distance comparison t test. Asthma severity in atopic children was associated with fungal community composition (P = .001). By using logistic regression, asthma severity in nonatopic children was associated with total fungal concentration (odds ratio, 2.40; 95% CI, 1.06-5.44). The fungal genus Volutella was associated with increased asthma severity in atopic children (P = .0001, q = 0.04). The yeast genera Kondoa might be protective; Cryptococcus species might also affect asthma severity. CONCLUSION: Asthma severity among this cohort of children was associated with microbial exposure, and associations differed based on atopic status.

Effect of Fluoroquinolones and Macrolides on Eradication and Resistance of Haemophilus influenzae in Chronic Obstructive Pulmonary Disease.

Little is known about the effect of antibiotics on eradication of carriage and development of resistance in Haemophilus influenzae in individuals with chronic obstructive pulmonary disease (COPD). Our goals were to assess antibiotic susceptibilities, prevalence of resistance genes, and development of resistance in H. influenzae and to evaluate the effect of macrolide and fluoroquinolone administration on H. influenzae eradication. Data were from a 15-year longitudinal study of COPD. Genome sequence data were used to determine genotype and identify resistance genes. MICs of antibiotics were determined by reference broth microdilution. Generalized linear mixed models were used to evaluate associations between antibiotic use and H. influenzae eradication. We examined 267 H. influenzae isolates from 77 individuals. All newly acquired H. influenzae isolates were susceptible to azithromycin. Five of 27 (19%) strains developed 4-fold increases in azithromycin MICs and reached or exceeded the susceptibility breakpoint (≤4 µg/ml) during exposure. H. influenzae isolates were uniformly susceptible to ciprofloxacin, levofloxacin, and moxifloxacin (MIC90s of 0.015, 0.015, and 0.06, respectively); there were no mutations in quinolone resistance-determining regions. Fluoroquinolone administration was associated with increased H. influenzae eradication compared to macrolides (odds ratio [OR], 16.67; 95% confidence interval [CI], 2.67 to 104.09). There was no difference in H. influenzae eradication when comparing macrolide administration to no antibiotic (OR, 1.89; 95% CI, 0.43 to 8.30). Fluoroquinolones are effective in eradicating H. influenzae in individuals with COPD. Macrolides are ineffective in eradicating H. influenzae, and their use in COPD patients may lead to decreased macrolide susceptibility and resistance.

Association of sputum microbiota profiles with severity of community-acquired pneumonia in children.

BACKGROUND: Competitive interactions among bacteria in the respiratory tract microbiota influence which species can colonize and potentially contribute to pathogenesis of community-acquired pneumonia (CAP). However, understanding of the role of respiratory tract microbiota in the clinical course of pediatric CAP is limited. METHODS: We sought to compare microbiota profiles in induced sputum and nasopharyngeal/oropharyngeal (NP/OP) samples from children and to identify microbiota profiles associated with CAP severity. We used 16S ribosomal RNA sequencing and several measures of microbiota profiles, including principal component analysis (PCA), to describe the respiratory microbiota in 383 children, 6 months to <18 years, hospitalized with CAP. We examined associations between induced sputum and NP/OP microbiota profiles and CAP severity (hospital length of stay and intensive care unit admission) using logistic regression. RESULTS: Relative abundance of bacterial taxa differed in induced sputum and NP/OP samples. In children 6 months to < 5 years, the sputum PCA factor with high relative abundance of Actinomyces, Veillonella, Rothia, and Lactobacillales was associated with decreased odds of length of stay ≥ 4 days [adjusted odds ratio (aOR) 0.69; 95 % confidence interval (CI) 0.48-0.99]. The sputum factor with high relative abundance of Haemophilus and Pasteurellaceae was associated with increased odds of intensive care unit admission [aOR 1.52; 95 % CI 1.02-2.26]. In children 5 to < 18 years, the sputum factor with high relative abundance of Porphyromonadaceae, Bacteriodales, Lactobacillales, and Prevotella was associated with increased odds of length of stay ≥ 4 days [aOR 1.52; 95 % CI 1.02-2.26]. Taxa in NP/OP samples were not associated with CAP severity. CONCLUSION: Certain taxa in the respiratory microbiota, which were detected in induced sputum samples, are associated with the clinical course of CAP.

Dynamic changes in the Streptococcus pneumoniae transcriptome during transition from biofilm formation to invasive disease upon influenza A virus infection.

Streptococcus pneumoniae is a leading cause of infectious disease globally. Nasopharyngeal colonization occurs in biofilms and precedes infection. Prior studies have indicated that biofilm-derived pneumococci are avirulent. However, influenza A virus (IAV) infection releases virulent pneumococci from biofilms in vitro and in vivo. Triggers of dispersal include IAV-induced changes in the nasopharynx, such as increased temperature (fever) and extracellular ATP (tissue damage). We used whole-transcriptome shotgun sequencing (RNA-seq) to compare the S. pneumoniae transcriptome in biofilms, bacteria dispersed from biofilms after exposure to IAV, febrile-range temperature, or ATP, and planktonic cells grown at 37°C. Compared with biofilm bacteria, actively dispersed S. pneumoniae, which were more virulent in invasive disease, upregulated genes involved in carbohydrate metabolism. Enzymatic assays for ATP and lactate production confirmed that dispersed pneumococci exhibited increased metabolism compared to those in biofilms. Dispersed pneumococci also upregulated genes associated with production of bacteriocins and downregulated colonization-associated genes related to competence, fratricide, and the transparent colony phenotype. IAV had the largest impact on the pneumococcal transcriptome. Similar transcriptional differences were also observed when actively dispersed bacteria were compared with avirulent planktonic bacteria. Our data demonstrate complex changes in the pneumococcal transcriptome in response to IAV-induced changes in the environment. Our data suggest that disease is caused by pneumococci that are primed to move to tissue sites with altered nutrient availability and to protect themselves from the nasopharyngeal microflora and host immune response. These data help explain pneumococcal virulence after IAV infection and have important implications for studies of S. pneumoniae pathogenesis.

Household levels of nitrogen dioxide and pediatric asthma severity.

BACKGROUND: Adverse respiratory effects in children with asthma are associated with exposures to nitrogen dioxide (NO2). Levels indoors can be much higher than outdoors. Primary indoor sources of NO2 are gas stoves, which are used for cooking by one-third of U.S. households. We investigated the effects of indoor NO2 exposure on asthma severity among an ethnically and economically diverse sample of children, controlling for season and indoor allergen exposure. METHODS: Children 5-10 years of age with active asthma (n = 1,342) were recruited through schools in urban and suburban Connecticut and Massachusetts (2006-2009) for a prospective, year-long study with seasonal measurements of NO2 and asthma severity. Exposure to NO2 was measured passively for four, month-long, periods with Palmes tubes. Asthma morbidity was concurrently measured by a severity score and frequency of wheeze, night symptoms, and use of rescue medication. We used adjusted, hierarchical ordered logistic regression models to examine associations between household NO2 exposure and health outcomes. RESULTS: Every 5-fold increase in NO2 exposure above a threshold of 6 ppb was associated with a dose-dependent increase in risk of higher asthma severity score (odds ratio = 1.37 [95% confidence interval = 1.01-1.89]), wheeze (1.49 [1.09-2.03]), night symptoms (1.52 [1.16-2.00]), and rescue medication use (1.78 [1.33-2.38]). CONCLUSIONS: Asthmatic children exposed to NO2 indoors, at levels well below the U.S. Environmental Protection Agency outdoor standard (53 ppb), are at risk for increased asthma morbidity. Risks are not confined to inner city children, but occur at NO2 concentrations common in urban and suburban homes.

Paired Indoor and Outdoor Nitrogen Dioxide Associated With Childhood Asthma Outcomes in a Mixed Rural-Urban Setting: A Feasibility Study.

INTRODUCTION: Nitrogen dioxide (NO2) is known to be a trigger for asthma exacerbation. However, little is known about the role of seasonal variation in indoor and outdoor NO2 levels in childhood asthma in a mixed rural-urban setting of North America. METHODS: This prospective cohort study, as a feasibility study, included 62 families with children (5-17 years) that had diagnosed persistent asthma residing in Olmsted County, Minnesota. Indoor and outdoor NO2 concentrations were measured using passive air samples over 2 weeks in winter and 2 weeks in summer. We assessed seasonal variation in NO2 levels in urban and rural residential areas and the association with asthma control status collected from participants' asthma diaries during the study period. RESULTS: Outdoor NO2 levels were lower (median: 2.4 parts per billion (ppb) in summer, 3.9 ppb in winter) than the Environmental Protection Agency (EPA) annual standard (53 ppb). In winter, a higher level of outdoor NO2 was significantly associated with urban residential living area (P = .014) and lower socioeconomic status (SES) (P = .027). For both seasons, indoor NO2 was significantly higher (P < .05) in rural versus urban areas and in homes with gas versus electric stoves (P < .05). Asthma control status was not associated with level of indoor or outdoor NO2 in this cohort. CONCLUSIONS: NO2 levels were low in this mixed rural-urban community and not associated with asthma control status in this small feasibility study. Further research with a larger sample size is warranted for defining a lower threshold of NO2 concentration with health effect on asthma in mixed rural-urban settings.

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

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.

Relationship between birth weight and exposure to airborne fine particulate potassium and titanium during gestation.

Airborne particles are linked to numerous health impacts, including adverse pregnancy outcomes. Most studies of particles examined total mass, although the chemical structure of particles varies widely. We investigated whether mother's exposure to potassium (K) and titanium (Ti) components of airborne fine particulate matter (PM(2.5)) during pregnancy was associated with birth weight or risk of low birth weight (<2500 g) for term infants. The study population was 76,788 infants born in four counties in Connecticut and Massachusetts, US, for August 2000-February 2004. Both K and Ti were associated with birth weight. An interquartile range (IQR) increase K was associated with an 8.75% (95% confidence interval (CI): 1.24-16.8%) increase in risk of low birth weight. An IQR increase in Ti was associated with a 12.1% (95% CI: 3.55-21.4%) increase in risk of low birth weight, with an estimate of 6.41% (95% CI: -5.80-20.2%) for males and 16.4% (95% CI: 5.13-28.9%) for females. Results were robust to sensitivity analysis of first births only, but not adjustment by co-pollutants. Disentangling the effects of various chemical components is challenging because of the covariance among some components due to similar sources. Central effect estimates for infants of African-American mothers were higher than those of white mothers, although the confidence intervals overlapped. Our results indicate that exposure to airborne potassium and titanium during pregnancy is associated with lower birth weight. Associations may relate to chemical components of sources producing K and Ti.

Household mold and dust allergens: exposure, sensitization and childhood asthma morbidity.

BACKGROUND: Few studies address concurrent exposures to common household allergens, specific allergen sensitization and childhood asthma morbidity. OBJECTIVE: To identify levels of allergen exposures that trigger asthma exacerbations in sensitized individuals. METHODS: We sampled homes for common indoor allergens (fungi, dust mites (Der p 1, Der f 1), cat (Fel d 1), dog (Can f 1) and cockroach (Bla g 1)) for levels associated with respiratory responses among school-aged children with asthma (N=1233) in a month-long study. Blood samples for allergy testing and samples of airborne fungi and settled dust were collected at enrollment. Symptoms and medication use were recorded on calendars. Combined effects of specific allergen sensitization and level of exposure on wheeze, persistent cough, rescue medication use and a 5-level asthma severity score were examined using ordered logistic regression. RESULTS: Children sensitized and exposed to any Penicillium experienced increased risk of wheeze (odds ratio [OR] 2.12 95% confidence interval [CI] 1.12, 4.04), persistent cough (OR 2.01 95% CI 1.05, 3.85) and higher asthma severity score (OR 1.99 95% CI 1.06, 3.72) compared to those not sensitized or sensitized but unexposed. Children sensitized and exposed to pet allergen were at significantly increased risk of wheeze (by 39% and 53% for Fel d 1>0.12 µg/g and Can f 1>1.2 µg/g, respectively). Increased rescue medication use was significantly associated with sensitization and exposure to Der p 1>0.10 µg/g (by 47%) and Fel d 1>0.12 µg/g (by 32%). CONCLUSION: Asthmatic children sensitized and exposed to low levels of common household allergens Penicillium, Der p 1, Fel d 1 and Can f 1 are at significant risk for increased morbidity.

Viral-bacterial interactions and risk of acute otitis media complicating upper respiratory tract infection.

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 χ(2) test). Children with high respiratory syncytial virus loads (≥3.16 × 10(7) 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.

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.

Integrated exposure modeling: a model using GIS and GLM.

Traffic exhaust is a source of air contaminants that have adverse health effects. Quantification of traffic as an exposure variable is complicated by aerosol dispersion related to variation in layout of roads, traffic density, meteorology, and topography. A statistical model is presented that uses Geographic Information Systems (GIS) technology to incorporate variables into a generalized linear model that estimates distribution of traffic-related pollution. Exposure from a source is expressed as an integral of a function proportional to average daily traffic and a nonparametric dispersion function, which takes the form of a step, polynomial, or spline model. The method may be applied using standard regression techniques for fitting generalized linear models. Modifiers of pollutant dispersion such as wind direction, meteorology, and landscape features can also be included. Two examples are given to illustrate the method. The first employs data from a study in which NO(2) (a known pollutant from automobile exhaust) was monitored outside of 138 Connecticut homes, providing a model for estimating NO(2) exposure. In the second example, estimated levels of nitrogen dioxide (NO(2)) from the model, as well as a separate spatial model, were used to analyze traffic-related health effects in a study of 761 infants.

Modeling effects of traffic and landscape characteristics on ambient nitrogen dioxide levels in Connecticut.

An integrated exposure model was developed that estimates nitrogen dioxide (NO(2)) concentration at residences using geographic information systems (GIS) and variables derived within residential buffers representing traffic volume and landscape characteristics including land use, population density and elevation. Multiple measurements of NO(2) taken outside of 985 residences in Connecticut were used to develop the model. A second set of 120 outdoor NO(2) measurements as well as cross-validation were used to validate the model. The model suggests that approximately 67% of the variation in NO(2) levels can be explained by: traffic and land use primarily within 2 km of a residence; population density; elevation; and time of year. Potential benefits of this model for health effects research include improved spatial estimations of traffic-related pollutant exposure and reduced need for extensive pollutant measurements. The model, which could be calibrated and applied in areas other than Connecticut, has importance as a tool for exposure estimation in epidemiological studies of traffic-related air pollution.

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 mother's education. RESULTS: Der p 1 house dust mite allergen concentration of 2.0 microg/g or more from the main room and the child's 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.

Microbial interactions during upper respiratory tract infections.

Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus often colonize the nasopharynx. Children are susceptible to bacterial infections during or soon after upper respiratory tract infection (URI). We describe colonization with these 4 bacteria species alone or in combination during URI. Data were from a prospective cohort of healthy children 6 to 36 months of age followed up for 1 year. Analyses of 968 swabs from 212 children indicated that S. pneumoniae colonization is negatively associated with colonization by H. influenzae. Competitive interactions shifted when H. influenzae and M. catarrhalis colonized together. In this situation, the likelihood of colonization with all 3 species is higher. Negative associations were identified between S. pneumoniae and S. aureus and between H. influenzae and S. aureus. Polymicrobial interactions differed by number and species of bacteria present. Antimicrobial therapy and vaccination strategies targeting specific bacterial species may alter the flora in unforeseen ways.

Respiratory symptoms among infants at risk for asthma: association with surfactant protein A haplotypes.

BACKGROUND: We examined the association between single nucleotide polymorphisms (SNPs) in loci encoding surfactant protein A (SFTPA) and risk of wheeze and persistent cough during the first year of life among a cohort of infants at risk for developing asthma. METHODS: Between September 1996 and December 1998, mothers of newborn infants were invited to participate if they had an older child with clinician-diagnosed asthma. Each mother was given a standardized questionnaire within 4 months of her infant's birth. Infant respiratory symptoms were collected during quarterly telephone interviews at 6, 9 and 12 months of age. Due to the association of SFTPA polymorphisms and race/ethnicity, analyses were restricted to 221 white infants for whom whole blood and respiratory data were available. Ordered logistic regression models were used to examine the association between respiratory symptom frequency and SFTPA haplotypes. RESULTS: The 6A allele haplotype of SFTPA1, with an estimated frequency of 6% among our study infants, was associated with an increased risk of persistent cough (OR 3.69, 95% CI 1.71, 7.98) and wheeze (OR 4.72, 95% CI 2.20, 10.11). The 6A/1A haplotype of SFTPA, found among approximately 5% of the infants, was associated with an increased risk of persistent cough (OR 3.20, 95% CI 1.39, 7.36) and wheeze (OR 3.25, 95% CI 1.43, 7.37). CONCLUSION: Polymorphisms within SFTPA loci may be associated with wheeze and persistent cough in white infants at risk for asthma. These associations require replication and exploration in other ethnic/racial groups.