Reducing Hospitalizations and Multidrug-Resistant Organisms via Regional Decolonization in Hospitals and Nursing Homes.

Importance: Infections due to multidrug-resistant organisms (MDROs) are associated with increased morbidity, mortality, length of hospitalization, and health care costs. Regional interventions may be advantageous in mitigating MDROs and associated infections. Objective: To evaluate whether implementation of a decolonization collaborative is associated with reduced regional MDRO prevalence, incident clinical cultures, infection-related hospitalizations, costs, and deaths. Design, Setting, and Participants: This quality improvement study was conducted from July 1, 2017, to July 31, 2019, across 35 health care facilities in Orange County, California. Exposures: Chlorhexidine bathing and nasal iodophor antisepsis for residents in long-term care and hospitalized patients in contact precautions (CP). Main Outcomes and Measures: Baseline and end of intervention MDRO point prevalence among participating facilities; incident MDRO (nonscreening) clinical cultures among participating and nonparticipating facilities; and infection-related hospitalizations and associated costs and deaths among residents in participating and nonparticipating nursing homes (NHs). Results: Thirty-five facilities (16 hospitals, 16 NHs, 3 long-term acute care hospitals [LTACHs]) adopted the intervention. Comparing decolonization with baseline periods among participating facilities, the mean (SD) MDRO prevalence decreased from 63.9% (12.2%) to 49.9% (11.3%) among NHs, from 80.0% (7.2%) to 53.3% (13.3%) among LTACHs (odds ratio [OR] for NHs and LTACHs, 0.48; 95% CI, 0.40-0.57), and from 64.1% (8.5%) to 55.4% (13.8%) (OR, 0.75; 95% CI, 0.60-0.93) among hospitalized patients in CP. When comparing decolonization with baseline among NHs, the mean (SD) monthly incident MDRO clinical cultures changed from 2.7 (1.9) to 1.7 (1.1) among participating NHs, from 1.7 (1.4) to 1.5 (1.1) among nonparticipating NHs (group × period interaction reduction, 30.4%; 95% CI, 16.4%-42.1%), from 25.5 (18.6) to 25.0 (15.9) among participating hospitals, from 12.5 (10.1) to 14.3 (10.2) among nonparticipating hospitals (group × period interaction reduction, 12.9%; 95% CI, 3.3%-21.5%), and from 14.8 (8.6) to 8.2 (6.1) among LTACHs (all facilities participating; 22.5% reduction; 95% CI, 4.4%-37.1%). For NHs, the rate of infection-related hospitalizations per 1000 resident-days changed from 2.31 during baseline to 1.94 during intervention among participating NHs, and from 1.90 to 2.03 among nonparticipating NHs (group × period interaction reduction, 26.7%; 95% CI, 19.0%-34.5%). Associated hospitalization costs per 1000 resident-days changed from $64 651 to $55 149 among participating NHs and from $55 151 to $59 327 among nonparticipating NHs (group × period interaction reduction, 26.8%; 95% CI, 26.7%-26.9%). Associated hospitalization deaths per 1000 resident-days changed from 0.29 to 0.25 among participating NHs and from 0.23 to 0.24 among nonparticipating NHs (group × period interaction reduction, 23.7%; 95% CI, 4.5%-43.0%). Conclusions and Relevance: A regional collaborative involving universal decolonization in long-term care facilities and targeted decolonization among hospital patients in CP was associated with lower MDRO carriage, infections, hospitalizations, costs, and deaths.

Impact of universal chlorhexidine bathing with or without COVID-19 intensive training on staff and resident COVID-19 case rates in nursing homes.

We evaluated whether universal chlorhexidine bathing (decolonization) with or without COVID-19 intensive training impacted COVID-19 rates in 63 nursing homes (NHs) during the 2020-2021 Fall/Winter surge. Decolonization was associated with a 43% lesser rise in staff case-rates (P < .001) and a 52% lesser rise in resident case-rates (P < .001) versus control.

Evaluating barriers and potential solutions to speaking up about coronavirus disease 2019 (COVID-19) symptoms: A survey among nursing home workers.

OBJECTIVE: Quantify the frequency and drivers of unreported coronavirus disease 2019 (COVID-19) symptoms among nursing home (NH) staff. DESIGN: Confidential telephone survey. SETTING: The study was conducted in 70 NHs in Orange County, California, December 2020-February 2022. PARTICIPANTS: The study included 120 NH staff with COVID-19. METHODS: We designed a 40-item telephone survey of NH staff to assess COVID-19 symptom reporting behavior and types of barriers [monetary, logistic, and emotional (fear or stigma)] and facilitators of symptom reporting using 5-point Likert scales. Summary statistics, reliability of survey constructs, and construct and discriminant validity were assessed. RESULTS: Overall, 49% of surveys were completed during the 2020-2021 COVID-19 winter wave and 51% were completed during severe acute respiratory coronavirus virus 2 (SARS-CoV-2) δ (delta)/ (omicron) waves, with a relatively even distribution of certified nursing assistants, licensed vocational or registered nurses, and nonfrontline staff. Most COVID-19 cases (71%) were detected during mandated weekly NH surveillance testing and most staff (67%) had ≥1 symptom prior to their test. Only 34% of those with symptoms disclosed their symptom to a supervisor. Responses were consistent across 8 discrete survey constructs with Cronbach α > 0.70. In the first wave of the pandemic, fear and lack of knowledge were drivers of symptom reporting. In later waves, adequate staffing and sick days were drivers of symptom reporting. COVID-19 help lines and encouragement from supervisors facilitated symptom reporting and testing. CONCLUSIONS: Mandatory COVID-19 testing for NH staff is key to identifying staff COVID-19 cases due to reluctance to speak up about existing symptoms. Active encouragement from supervisors to report symptoms and stay home when ill was a major driver of symptom reporting and resultant infection prevention and worker safety measures.

Decolonization in Nursing Homes to Prevent Infection and Hospitalization.

BACKGROUND: Nursing home residents are at high risk for infection, hospitalization, and colonization with multidrug-resistant organisms. METHODS: We performed a cluster-randomized trial of universal decolonization as compared with routine-care bathing in nursing homes. The trial included an 18-month baseline period and an 18-month intervention period. Decolonization entailed the use of chlorhexidine for all routine bathing and showering and administration of nasal povidone-iodine twice daily for the first 5 days after admission and then twice daily for 5 days every other week. The primary outcome was transfer to a hospital due to infection. The secondary outcome was transfer to a hospital for any reason. An intention-to-treat (as-assigned) difference-in-differences analysis was performed for each outcome with the use of generalized linear mixed models to compare the intervention period with the baseline period across trial groups. RESULTS: Data were obtained from 28 nursing homes with a total of 28,956 residents. Among the transfers to a hospital in the routine-care group, 62.2% (the mean across facilities) were due to infection during the baseline period and 62.6% were due to infection during the intervention period (risk ratio, 1.00; 95% confidence interval [CI], 0.96 to 1.04). The corresponding values in the decolonization group were 62.9% and 52.2% (risk ratio, 0.83; 95% CI, 0.79 to 0.88), for a difference in risk ratio, as compared with routine care, of 16.6% (95% CI, 11.0 to 21.8; P<0.001). Among the discharges from the nursing home in the routine-care group, transfer to a hospital for any reason accounted for 36.6% during the baseline period and for 39.2% during the intervention period (risk ratio, 1.08; 95% CI, 1.04 to 1.12). The corresponding values in the decolonization group were 35.5% and 32.4% (risk ratio, 0.92; 95% CI, 0.88 to 0.96), for a difference in risk ratio, as compared with routine care, of 14.6% (95% CI, 9.7 to 19.2). The number needed to treat was 9.7 to prevent one infection-related hospitalization and 8.9 to prevent one hospitalization for any reason. CONCLUSIONS: In nursing homes, universal decolonization with chlorhexidine and nasal iodophor led to a significantly lower risk of transfer to a hospital due to infection than routine care. (Funded by the Agency for Healthcare Research and Quality; Protect ClinicalTrials.gov number, NCT03118232.).

Impact of Alzheimer's disease and related dementias (ADRD) on the quality of room cleaning in nursing homes.

Persons with Alzheimer's disease and related dementias (ADRD) are prone to receiving reduced quality of care. We compared the quality of room cleaning of rooms with ADRD residents and rooms with non-ADRD residents in nursing homes using an ultraviolet (UV) marker. ADRD status was associated with greater failure of UV marker removal (odds ratio, 1.68; 95% confidence interval, 1.04-2.71; P = .03).

Beyond Costs: Pragmatic Considerations for Pooling of SARS-CoV-2 Test Samples for Nursing Home Surveillance.

Pooling of samples can increase throughput and reduce costs for large-scale SARS-CoV-2 testing when incidence is low. In a cross-sectional study of serial SARS-CoV-2 sampling of staff and residents at three nursing homes, laboratory labor constraints limited the feasibility of pooling prior to the maximal incidence that favored cost savings. IMPORTANCE This study highlights the pragmatic considerations surrounding SARS-CoV-2 sample pooling beyond accuracy and costs. We performed a cost analysis to determine the percent positivity at which pooling would reduce costs versus single testing. We found that the need for a stable amount of daily work hours staffed by a highly trained workforce was a major limitation in pooling as test positivity increased. For the COVID-19 pandemic and future pandemic threats, laboratories should carefully consider the thresholds at which sample pooling is beneficial, with a particular focus on the impact on laboratory staff.

Post-discharge decolonization of patients harboring methicillin-resistant Staphylococcus aureus (MRSA) USA300 strains: secondary analysis of the CLEAR Trial.

The CLEAR Trial recently found that decolonization reduced infections and hospitalizations in MRSA carriers in the year following hospital discharge. In this secondary analysis, we explored whether decolonization had a similar benefit in the subgroup of trial participants who harbored USA300, using two different definitions for the USA300 strain-type.

Modeling Interventions to Reduce the Spread of Multidrug-Resistant Organisms Between Health Care Facilities in a Region.

Importance: Multidrug-resistant organisms (MDROs) can spread across health care facilities in a region. Because of limited resources, certain interventions can be implemented in only some facilities; thus, decision-makers need to evaluate which interventions may be best to implement. Objective: To identify a group of target facilities and assess which MDRO intervention would be best to implement in the Shared Healthcare Intervention to Eliminate Life-threatening Dissemination of MDROs in Orange County, a large regional public health collaborative in Orange County, California. Design, Setting, and Participants: An agent-based model of health care facilities was developed in 2016 to simulate the spread of methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Enterobacteriaceae (CRE) for 10 years starting in 2010 and to simulate the use of various MDRO interventions for 3 years starting in 2017. All health care facilities (23 hospitals, 5 long-term acute care hospitals, and 74 nursing homes) serving adult inpatients in Orange County, California, were included, and 42 target facilities were identified via network analyses. Exposures: Increasing contact precaution effectiveness, increasing interfacility communication about patients' MDRO status, and performing decolonization using antiseptic bathing soap and a nasal product in a specific group of target facilities. Main Outcomes and Measures: MRSA and CRE prevalence and number of new carriers (ie, transmission events). Results: Compared with continuing infection control measures used in Orange County as of 2017, increasing contact precaution effectiveness from 40% to 64% in 42 target facilities yielded relative reductions of 0.8% (range, 0.5%-1.1%) in MRSA prevalence and 2.4% (range, 0.8%-4.6%) in CRE prevalence in health care facilities countywide after 3 years, averting 761 new MRSA transmission events (95% CI, 756-765 events) and 166 new CRE transmission events (95% CI, 158-174 events). Increasing interfacility communication of patients' MDRO status to 80% in these target facilities produced no changes in the prevalence or transmission of MRDOs. Implementing decolonization procedures (clearance probability: 39% in hospitals, 27% in long-term acute care facilities, and 3% in nursing homes) yielded a relative reduction of 23.7% (range, 23.5%-23.9%) in MRSA prevalence, averting 3515 new transmission events (95% CI, 3509-3521 events). Increasing the effectiveness of antiseptic bathing soap to 48% yielded a relative reduction of 39.9% (range, 38.5%-41.5%) in CRE prevalence, averting 1435 new transmission events (95% CI, 1427-1442 events). Conclusions and Relevance: The findings of this study highlight the ways in which modeling can inform design of regional interventions and suggested that decolonization would be the best strategy for the Shared Healthcare Intervention to Eliminate Life-threatening Dissemination of MDROs in Orange County.

Impact of empiric antibiotics for methicillin-resistant Staphylococcus aureus (MRSA) infection and associated Clostridioides difficile infection (CDI) risk: Secondary analysis of the CLEAR trial.

We performed secondary analyses of a postdischarge decolonization trial of MRSA carriers that reduced MRSA infection and hospitalization by 30%. Hospitalized MRSA infection was associated with 7.9 days of non-MRSA antibiotics and CDI in 3.9%. Preventing MRSA infection and associated hospitalization may reduce antibiotic use and CDI incidence.

High Prevalence of Multidrug-Resistant Organism Colonization in 28 Nursing Homes: An "Iceberg Effect".

OBJECTIVE: Determine the prevalence of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus spp. (VRE), extended-spectrum beta-lactamase producing organisms (ESBLs), and carbapenem-resistant Enterobacteriaceae (CRE) among residents and in the environment of nursing homes (NHs). DESIGN: Point prevalence sampling of residents and environmental sampling of high-touch objects in resident rooms and common areas. SETTING: Twenty-eight NHs in Southern California from 2016 to 2017. PARTICIPANTS: NH participants in Project PROTECT, a cluster-randomized trial of enhanced bathing and decolonization vs routine care. METHODS: Fifty residents were randomly sampled per NH. Twenty objects were sampled, including 5 common room objects plus 5 objects in each of 3 rooms (ambulatory, total care, and dementia care residents). RESULTS: A total of 2797 swabs were obtained from 1400 residents in 28 NHs. Median prevalence of multidrug-resistant organism (MDRO) carriage per NH was 50% (range: 24%-70%). Median prevalence of specific MDROs were as follows: MRSA, 36% (range: 20%-54%); ESBL, 16% (range: 2%-34%); VRE, 5% (range: 0%-30%); and CRE, 0% (range: 0%-8%). A median of 45% of residents (range: 24%-67%) harbored an MDRO without a known MDRO history. Environmental MDRO contamination was found in 74% of resident rooms and 93% of common areas. CONCLUSIONS AND IMPLICATIONS: In more than half of the NHs, more than 50% of residents were colonized with MDROs of clinical and public health significance, most commonly MRSA and ESBL. Additionally, the vast majority of resident rooms and common areas were MDRO contaminated. The unknown submerged portion of the iceberg of MDRO carriers in NHs may warrant changes to infection prevention and control practices, particularly high-fidelity adoption of universal strategies such as hand hygiene, environmental cleaning, and decolonization.

Errors in antibiotic transitions between hospital and nursing home: How often do they occur?

We performed systematic review on 40 paired hospital and nursing home charts from a clinical trial to evaluate the fidelity of transitions of care among those discharged on antibiotics. We found that 30% of transitions included an inappropriate change to the patient's antibiotic plan of care.

Decolonization to Reduce Postdischarge Infection Risk among MRSA Carriers.

BACKGROUND: Hospitalized patients who are colonized with methicillin-resistant Staphylococcus aureus (MRSA) are at high risk for infection after discharge. METHODS: We conducted a multicenter, randomized, controlled trial of postdischarge hygiene education, as compared with education plus decolonization, in patients colonized with MRSA (carriers). Decolonization involved chlorhexidine mouthwash, baths or showers with chlorhexidine, and nasal mupirocin for 5 days twice per month for 6 months. Participants were followed for 1 year. The primary outcome was MRSA infection as defined according to Centers for Disease Control and Prevention (CDC) criteria. Secondary outcomes included MRSA infection determined on the basis of clinical judgment, infection from any cause, and infection-related hospitalization. All analyses were performed with the use of proportional-hazards models in the per-protocol population (all participants who underwent randomization, met the inclusion criteria, and survived beyond the recruitment hospitalization) and as-treated population (participants stratified according to adherence). RESULTS: In the per-protocol population, MRSA infection occurred in 98 of 1063 participants (9.2%) in the education group and in 67 of 1058 (6.3%) in the decolonization group; 84.8% of the MRSA infections led to hospitalization. Infection from any cause occurred in 23.7% of the participants in the education group and 19.6% of those in the decolonization group; 85.8% of the infections led to hospitalization. The hazard of MRSA infection was significantly lower in the decolonization group than in the education group (hazard ratio, 0.70; 95% confidence interval [CI], 0.52 to 0.96; P=0.03; number needed to treat to prevent one infection, 30; 95% CI, 18 to 230); this lower hazard led to a lower risk of hospitalization due to MRSA infection (hazard ratio, 0.71; 95% CI, 0.51 to 0.99). The decolonization group had lower likelihoods of clinically judged infection from any cause (hazard ratio, 0.83; 95% CI, 0.70 to 0.99) and infection-related hospitalization (hazard ratio, 0.76; 95% CI, 0.62 to 0.93); treatment effects for secondary outcomes should be interpreted with caution owing to a lack of prespecified adjustment for multiple comparisons. In as-treated analyses, participants in the decolonization group who adhered fully to the regimen had 44% fewer MRSA infections than the education group (hazard ratio, 0.56; 95% CI, 0.36 to 0.86) and had 40% fewer infections from any cause (hazard ratio, 0.60; 95% CI, 0.46 to 0.78). Side effects (all mild) occurred in 4.2% of the participants. CONCLUSIONS: Postdischarge MRSA decolonization with chlorhexidine and mupirocin led to a 30% lower risk of MRSA infection than education alone. (Funded by the AHRQ Healthcare-Associated Infections Program and others; ClinicalTrials.gov number, NCT01209234 .).

The SHIELD Orange County Project: Multidrug-resistant Organism Prevalence in 21 Nursing Homes and Long-term Acute Care Facilities in Southern California.

BACKGROUND: Multidrug-resistant organisms (MDROs) spread between hospitals, nursing homes (NHs), and long-term acute care facilities (LTACs) via patient transfers. The Shared Healthcare Intervention to Eliminate Life-threatening Dissemination of MDROs in Orange County is a regional public health collaborative involving decolonization at 38 healthcare facilities selected based on their high degree of patient sharing. We report baseline MDRO prevalence in 21 NHs/LTACs. METHODS: A random sample of 50 adults for 21 NHs/LTACs (18 NHs, 3 LTACs) were screened for methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus spp. (VRE), extended-spectrum ß-lactamase-producing organisms (ESBL), and carbapenem-resistant Enterobacteriaceae (CRE) using nares, skin (axilla/groin), and peri-rectal swabs. Facility and resident characteristics associated with MDRO carriage were assessed using multivariable models clustering by person and facility. RESULTS: Prevalence of MDROs was 65% in NHs and 80% in LTACs. The most common MDROs in NHs were MRSA (42%) and ESBL (34%); in LTACs they were VRE (55%) and ESBL (38%). CRE prevalence was higher in facilities that manage ventilated LTAC patients and NH residents (8% vs <1%, P < .001). MDRO status was known for 18% of NH residents and 49% of LTAC patients. MDRO-colonized adults commonly harbored additional MDROs (54% MDRO+ NH residents and 62% MDRO+ LTACs patients). History of MRSA (odds ratio [OR] = 1.7; confidence interval [CI]: 1.2, 2.4; P = .004), VRE (OR = 2.1; CI: 1.2, 3.8; P = .01), ESBL (OR = 1.6; CI: 1.1, 2.3; P = .03), and diabetes (OR = 1.3; CI: 1.0, 1.7; P = .03) were associated with any MDRO carriage. CONCLUSIONS: The majority of NH residents and LTAC patients harbor MDROs. MDRO status is frequently unknown to the facility. The high MDRO prevalence highlights the need for prevention efforts in NHs/LTACs as part of regional efforts to control MDRO spread.

Impact of Policies on the Rise in Sepsis Incidence, 2000-2010.

BACKGROUND: Sepsis hospitalizations have increased dramatically in the last decade. It is unclear whether this represents an actual rise in sepsis illness or improved capture by coding. We evaluated the impact of Centers of Medicare and Medicaid Services (CMS) guidance after newly introduced sepsis codes and medical severity diagnosis-related group (MS-DRG) systems on sepsis trends. METHODS: In this retrospective cohort study of California hospitalizations from January 2000 to December 2010, sepsis was identified by International Classification of Diseases, Ninth Revision (ICD-9) coding (Dombrovskiy method). Sepsis-associated mortality rates were calculated. Logistic regression models evaluated variables associated with sepsis and mortality. Segmented regression time series analysis assessed changes in sepsis frequency for (1) baseline (January 2000 to September 2003); (2) post-CMS guidelines on sepsis coding (October 2003 to September 2007); and (3) after the introduction of MS-DRG (October 2007 to December 2010). RESULTS: Annual hospitalizations with sepsis diagnoses tripled within a decade, from 21.1 to 59.9 cases per 1000 admissions, with a 2.8- and 2.0-fold increase in severe and nonsevere sepsis, respectively, whereas annual admissions remained unchanged and sepsis-associated mortality decreased. Greatest increases were seen for severe sepsis present on admission (3.8-fold increase). Increases in sepsis were temporally correlated with CMS coding guidance and MS-DRG introduction after adjustment for comorbidity and other factors. CONCLUSIONS: Sepsis rate increases were associated with introduction of CMS-issued guidance for new sepsis ICD-9 coding and MS-DRGs. Coding artifact ("up-capture" of less severely ill septic patients) may be contributing to the apparent rise in sepsis incidence and decline in mortality. Epidemiologic trends based on administrative data should account for policy-related effects.

Nrf2-related gene expression and exposure to traffic-related air pollution in elderly subjects with cardiovascular disease: An exploratory panel study.

Gene expression changes are linked to air pollutant exposures in in vitro and animal experiments. However, limited data are available on how these outcomes relate to ambient air pollutant exposures in humans. We performed an exploratory analysis testing whether gene expression levels were associated with air pollution exposures in a Los Angeles area cohort of elderly subjects with coronary artery disease. Candidate genes (35) were selected from published studies of gene expression-pollutant associations. Expression levels were measured weekly in 43 subjects (≤ 12 weeks) using quantitative PCR. Exposures included gaseous pollutants O3, nitrogen oxides (NOx), and CO; particulate matter (PM) pollutants elemental and black carbon (EC, BC); and size-fractionated PM mass. We measured organic compounds from PM filter extracts, including polycyclic aromatic hydrocarbons (PAHs), and determined the in vitro oxidative potential of particle extracts. Associations between exposures and gene expression levels were analyzed using mixed-effects regression models. We found positive associations of traffic-related pollutants (EC, BC, primary organic carbon, PM 0.25-2.5 PAH and/or PM 0.25 PAH, and NOx) with NFE2L2, Nrf2-mediated genes (HMOX1, NQO1, and SOD2), CYP1B1, IL1B, and SELP. Findings suggest that NFE2L2 gene expression links associations of traffic-related air pollution with phase I and II enzyme genes at the promoter transcription level.

Relations of exhaled nitric oxide and FEV1 to personal endotoxin exposure in schoolchildren with asthma.

BACKGROUND: Asthma prevalence and acute exacerbations have been associated with endotoxin exposure. However, there are limited data on relations between acute asthma outcomes in children and personal exposure to endotoxin or whether this relation is modified by personal air pollution exposures. METHODS: We made repeated measurements of the fractional concentration of exhaled NO (FeNO), forced expiratory volume in 1 s (FEV1) and personal endotoxin exposures in patients with persistent asthma aged 9-18 years, each of whom was followed for 10 consecutive days in Riverside and Whittier, California. Endotoxin was measured in PM2.5, and simultaneously we measured personal exposure to air pollutants: NO2 and PM2.5 mass, elemental carbon and organic carbon. Endotoxin exposure-response relations and interactions between endotoxin and air pollutants were analysed with mixed models controlling for personal temperature, humidity and the 10-day period. RESULTS: Neither percent-predicted FEV1 nor FeNO was associated with personal endotoxin overall; however, endotoxin was associated with FEV1 among patients with average percent-predicted FEV1<80%. When NO2 was above its median, FeNO increased by 2.2% (95% CI -0.8% to 5.2%) for an interquartile increase in personal endotoxin, whereas FeNO was lower by -1.8% (95% CI -4% to 0.5%) when NO2 was≤its median. However, this is out of 12 interaction tests between personal endotoxin and a binary air pollutant for each outcome (FEV1 and FeNO), and there were no interactions with any continuous-scaled pollutant. CONCLUSIONS: Personal endotoxin exposure was not associated with acute daily changes in FeNO or FEV1 in a cohort panel of schoolchildren with asthma, except for decreased FEV1 among patients with more severe asthma (percent-predicted FEV1<80%). There was limited evidence of effect modification of endotoxin by personal exposure to air pollution.

Asthma morbidity and ambient air pollution: effect modification by residential traffic-related air pollution.

BACKGROUND: Ambient air pollution has been associated with asthma-related hospital admissions and emergency department visits (hospital encounters). We hypothesized that higher individual exposure to residential traffic-related air pollutants would enhance these associations. METHODS: We studied 11,390 asthma-related hospital encounters among 7492 subjects 0-18 years of age living in Orange County, California. Ambient exposures were measured at regional air monitoring stations. Seasonal average traffic-related exposures (PM2.5, ultrafine particles, NOx, and CO) were estimated near subjects' geocoded residences for 6-month warm and cool seasonal periods, using dispersion models based on local traffic within 500 m radii. Associations were tested in case-crossover conditional logistic regression models adjusted for temperature and humidity. We assessed effect modification by seasonal residential traffic-related air pollution exposures above and below median dispersion-modeled exposures. Secondary analyses considered effect modification by traffic exposures within race/ethnicity and insurance group strata. RESULTS: Asthma morbidity was positively associated with daily ambient O3 and PM2.5 in warm seasons and with CO, NOx, and PM2.5 in cool seasons. Associations with CO, NOx, and PM2.5 were stronger among subjects living at residences with above-median traffic-related exposures, especially in cool seasons. Secondary analyses showed no consistent differences in association, and 95% confidence intervals were wide, indicating a lack of precision for estimating these highly stratified associations. CONCLUSIONS: Associations of asthma with ambient air pollution were enhanced among subjects living in homes with high traffic-related air pollution. This may be because of increased susceptibility (greater asthma severity) or increased vulnerability (meteorologic amplification of local vs. correlated ambient exposures).

Relations between isoprene and nitric oxide in exhaled breath and the potential influence of outdoor ozone: a pilot study.

The role of endogenous isoprene in the human body, if any, is unclear because previous research is inconsistent and mechanistic evidence for the biologic function of isoprene is lacking. Given previous evidence that exhaled isoprene is elevated in systemic inflammatory states, we hypothesized that exhaled isoprene would be positively associated with a breath biomarker of airway inflammation, the fractional concentration of exhaled nitric oxide (FENO). We examined relationships of exhaled breath isoprene with FENO and with outdoor ozone given that ozone chemically reacts with isoprene and has been positively associated with FENO in past studies. Sixteen elderly subjects were followed with ≤12 weekly exhaled hydrocarbon and FENO collections at the subjects' retirement community. Outdoor ozone concentrations were measured continuously on site. Mixed-effects regression analyses tested relations of FENO with isoprene, and FENO and isoprene with ozone, adjusted for temperature. We found FENO was inversely associated with isoprene, and this was not confounded by ozone. Isoprene was inversely related to ozone. FENO was positively related to ozone and this relation was not confounded by isoprene. In contrast to hypothesized relations, we conclude that exhaled isoprene is inversely associated with FENO as well as outdoor ozone, which suggests possible protective ozone-scavenging functions of endogenous isoprene. Findings may indicate chemical reactions of isoprene oxidation by ozone and by hydroxyl radicals in the presence of O2 that is dependent on NO concentration. These preliminary results need to be confirmed in additional studies of human subjects, particularly as they apply to FENO monitoring in asthma.

Particulate air pollution, ambulatory heart rate variability, and cardiac arrhythmia in retirement community residents with coronary artery disease.

BACKGROUND: Decreased heart rate variability (HRV) has been associated with future cardiac morbidity and mortality and is often used as a marker of altered cardiac autonomic balance in studies of health effects of airborne particulate matter. Fewer studies have evaluated associations between air pollutants and cardiac arrhythmia. OBJECTIVES: We examined relationships between cardiac arrhythmias, HRV, and exposures to airborne particulate matter. METHODS: We measured HRV and arrhythmia with ambulatory electrocardiograms in a cohort panel study for up to 235 hr per participant among 50 nonsmokers with coronary artery disease who were ≥ 71 years of age and living in four retirement communities in the Los Angeles, California, Air Basin. Exposures included hourly outdoor gases, hourly traffic-related and secondary organic aerosol markers, and daily size-fractionated particle mass. We used repeated measures analyses, adjusting for actigraph-derived physical activity and heart rate, temperature, day of week, season, and community location. RESULTS: Ventricular tachycardia was significantly increased in association with increases in markers of traffic-related particles, secondary organic carbon, and ozone. Few consistent associations were observed for supraventricular tachycardia. Particulates were significantly associated with decreased ambulatory HRV only in the 20 participants using ACE (angiotensin I-converting enzyme) inhibitors. CONCLUSIONS: Although these data support the hypothesis that particulate exposures may increase the risk of ventricular tachycardia for elderly people with coronary artery disease, HRV was not associated with exposure in most of our participants. These results are consistent with previous findings in this cohort for systemic inflammation, blood pressure, and ST segment depression.