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Objective: To determine if the GSTM1 null genotype is a risk factor for increased inflammatory response to inhaled endotoxin.Methods: 35 volunteers who had undergone inhalation challenge with a 20 000 endotoxin unit dose of Clinical Center Reference Endotoxin (CCRE) were genotyped for the GSTM1 null polymorphism. Parameters of airway and systemic inflammation observed before and after challenge were compared in GSTM1 null (n=17) and GSTM1 (n=18) sufficient volunteers.Results: GSTM1 null volunteers had significantly increased circulating white blood cells (WBCs), polymorphonuclear neutrophils (PMNs), platelets and sputum PMNs (% sputum PMNs and PMNs/mg sputum) after CCRE challenge. GSTM1 sufficient volunteers had significant, but lower increases in circulating WBCs, PMNs and % sputum PMNs, and no increase in platelets or PMNs/mg sputum. Linear regression analysis adjusted for baseline values of the entire cohort revealed that the GSTM1 null genotype significantly increased circulating WBCs, platelets and % sputum PMNs after challenge.Conclusion: These data support the hypothesis that the GSTM1 null genotype is a risk factor for increased acute respiratory and systemic inflammatory response to inhaled CCRE. These data are consistent with other observations that the GSTM1 null genotype is associated with increased respiratory, systemic and cardiovascular effects linked to ambient air particulate matter exposure and indicate that the GSTM1 null genotype should be considered a risk factor for adverse health effects associated with exposure to environmental endotoxin. [ABSTRACT FROM AUTHOR]

Background: Affect recall is key to psychological assessment and decision-making. However, self-concepts (self-beliefs) may bias retrospective affect reports such that they deviate from lived experiences. Does this experience-memory gap apply to solitude experiences? We hypothesized that individuals misremember how they feel overall and when in solitude, in line with self-concepts of introversion, self-determined/not-self-determined solitude motivations, and independent/interdependent self-construal. A pilot study comparing retrospective to daily affect reports captured over 2 weeks (N = 104 UK university students) provided preliminary evidence of introversion and not-self-determined solitude shaping affect recall., Methods: In the main pre-registered study, participants aged 18-49 in the UK (N = 160) and Hong Kong (N = 159) reported their momentary affective states and social situations 5 times per day over 7 days, then recalled how they felt over the week., Results and Discussion: Individuals higher in self-determined solitude were more prone to retrospectively overestimate their high- and low-arousal positive affect in solitude and showed less overestimation/more underestimation of negative affect in solitude. Higher not-self-determined solitude was associated with overestimating loneliness, and higher interdependent self-construal with overestimating loneliness and energy levels, in solitude. Comparisons based on residence/ethnicity suggest culture influences solitude-seeking and affective memory. Implications for well-being and affect measurement are discussed., (© 2024 The Author(s). Journal of Personality published by Wiley Periodicals LLC.)

Older adults report greater affective well-being in solitude than younger adults, but prior findings are based on correlational designs. We aim to examine age differences in affective well-being in solitude using an experimental design and to examine conflict de-escalation as a potential mechanism. In Study 1, 207 participants were randomly assigned to either a solitude or a social interaction condition. In Study 2, 128 participants were randomly assigned to one of four conditions: solitude-escalation, solitude-de-escalation, interaction-escalation, and interaction de-escalation. After a 15-min solitude or social interaction period, they reported their affective experiences. In Study 1, older (vs. younger) adults reported more positive affect overall. This age-related difference was greater in the solitude (vs. social interaction) condition; older adults reported less negative affect than younger adults in the solitude, but not the social interaction, condition. In Study 2, older (vs. younger) participants reported more high-arousal positive affect in the solitude-escalation condition. This difference was not significant in conflict de-escalation conditions. Our studies provide causal evidence of the relationship between solitude and affective well-being and advance our understanding of motivations that explain why older adults maintain better affective well-being in solitude., (© 2024 International Association of Applied Psychology.)

This study investigated everyday associations between one key facet of mindfulness (allocating attention to the present moment) and pain. In Study 1, 89 community-dwelling adults (33-88 years; M age = 68.6) who had experienced a stroke provided 14 daily end-of-day present-moment awareness and pain ratings. In Study 2, 100 adults (50-85 years; M age = 67.0 years) provided momentary present-moment awareness and pain ratings three times daily for 10 days. Multi-level models showed that higher trait present-moment awareness was linked with lower overall pain (both studies). In Study 1, participants reported less pain on days on which they indicated higher present-moment awareness. In Study 2, only individuals with no post-secondary education reported less pain in moments when they indicated higher present-moment awareness. Findings add to previous research using global retrospective pain measures by showing that present-moment awareness might correlate with reduced pain experiences, assessed close in time to when they occur.

Background and Objectives: Extremely hot temperature affects psychological well-being negatively, especially for older adults with lower socioeconomic status (SES). The objectives of this study are to examine: (a) the impact of hot instantaneous temperature on older adults' emotional well-being and (b) whether meaningful engagement could reduce the above impact, particularly for those of lower SES., Research Design and Methods: We conducted a quantitative time-sampling study during hot-weather months (May-September) in 2021 and 2022. The sample comprises 344 participants aged 60 years or older ( M age = 67.15, SD age = 5.26) living in urban areas of Hong Kong, where hot days (daily maximum temperature ≥33°C) accounted for 23% of the study days. Participants reported positive and negative affect, and engagement in meaningful activities, three times a day over a 10-day period, and wore sensors that tracked the instantaneous temperature of their immediate environment. Multilevel modeling was employed to examine the impacts on affect from temperature, SES, and meaningful activity engagement., Results: Hotter instantaneous temperature predicted greater momentary negative affect and less positive affect immediately afterwards. Meaningful engagement significantly buffered against the affective impacts of hotter temperature, and this buffering effect was more salient among older adults of lower SES., Discussion and Implications: This study highlights the role of meaningful engagement in reducing the impact of hotter instantaneous temperature on older adults' emotional well-being, particularly for those of lower SES. Meaningful activity engagement may be capitalized on, as a strategy, to reduce climate-related social inequality., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Background: Although the majority of existing literature has suggested positive effects of housework on older adults' health and survival rate, the underlying mechanisms of such effects remain unclear. To address potential mechanisms, the present study examined the association between older adults' housework engagement and days of survival across 14 years and tested three potential mediation pathways in this association., Methods: Four thousand Hong Kong older adults (50% female; aged between 65 and 98 years) participated in a longitudinal study in which they reported initial housework engagement and health status across three domains (cognitive functioning, physical health, and mental health) at the baseline, and the numbers of days they survived over the subsequent 14-year period were recorded. Linear regression, Cox proportional hazard, and parallel mediation analyses were performed to examine the relationship between housework engagement and days survived, and the mediating effects of these three health factors., Results: The results showed a positive association between housework engagement and days survived after controlling for demographic variables (age, sex, education, marital status, subjective social status, and living alone). Physical health and mental health, but not cognitive functioning, partially mediated the relationship between housework engagement and days survived. The findings suggest that doing housework may contribute to longer survival by improving older adults' physical and mental health., Conclusion: The current study confirms positive relations of housework with health and mortality among Hong Kong older adults. As the first study examining the relationships and mediation pathways between doing housework and survival in later life, the findings advance our understanding of the mechanisms underlying the positive association between housework and mortality and provide insights for future daily-life health-promotion interventions for older adults., (© 2023. The Author(s).)

Loneliness is a recognized risk factor for morbidity and mortality across the adult life span including old age. Loneliness is a negative emotional experience that has been associated with social isolation, but loneliness may also be adaptive to the extent that it signals a need to socially reengage. To reconcile these seemingly contradictory findings, we unpack the timing of the underlying processes by distinguishing between transient and chronic loneliness in shaping prosocial behaviors. Using 10 days of electronic daily life assessments from 100 middle-aged and older adults ( M age = 67.0 years; 64.0% women), findings indicate that chronic loneliness moderates time-varying associations between transient loneliness and prosocial behavior. Simple slope results point to individual differences in daily loneliness-prosocial action associations. Specifically, adults high in chronic loneliness, but not those low in chronic loneliness, showed decreased prosocial behaviors on days with elevated transient loneliness. Findings suggest that chronic loneliness may elicit maladaptive responses to transient loneliness by hampering the use of opportunities to engage in prosocial behavior. Exploratory analyses point to fear of evaluation as a potential mechanism that is associated with increased loneliness and reduced prosocial behavior. Findings highlight the differential roles of transient and chronic loneliness in shaping prosocial activities in midlife and older adulthood, thereby providing a more nuanced picture as well as potential avenues for intervention. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Older adults spend much time in solitude (without social interaction), putting them at risk of loneliness, especially if aging outside their country of origin (e.g., Chinese immigrants to Canada). Yet, cultural contextual factors that may reduce loneliness in moments of solitude are poorly understood. This study sought to disentangle the roles of culture, immigration, and acculturation in solitude-loneliness associations across two countries. Community-dwelling adults aged 51-85 in Vancouver (N = 58 East Asian, N = 37 European/North American) and in Hong Kong (N = 56 East/Southeast Asian) completed approximately 30 ecological momentary assessments over 10 days on their current affect and social situations. Participants in Vancouver spent more time in solitude, desired solitude more, and felt less lonely overall than those in Hong Kong. Multilevel models revealed that moments of solitude felt lonelier than moments spent in social interaction, but only for individuals less acculturated to their host culture or not concurrently desiring solitude. Associations held regardless of host culture, cultural heritage, or immigration status. Findings suggest that solitude need not feel lonely if it happens by choice and if individuals feel connected with their host culture, for both immigrant older adults and those aging in their birth country., (© 2019 International Union of Psychological Science.)

With global aging, it is crucial to understand how older adults and the process of aging are viewed by members of society. These attitudes can often influence how older adults are treated. Since the Journal of Gerontology was founded, we have gained increasing insights into attitudes toward aging, with several notable research developments, including clearer conceptualization of different types of aging attitudes (e.g., life-domain-specific attitudes and self-perceptions of aging), a wider variety of measurements, better understanding of how different social determinants shape aging attitudes, and more sophisticated investigations of cultural variance and invariance in aging attitudes. In this article, we highlight these major shifts in the field of aging attitudes in the past 75 years, discuss the contributions of these developments, and point to potential future directions., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Despite a basic need for social connection, individuals across the adult lifespan sometimes seek solitude-a phenomenon that is not well understood. This study examined situational and affective correlates of solitude-seeking and how they may differ between middle-aged and older adults., Method: One hundred community-dwelling adults aged 50-85 years (64% female, 56% East Asian, 36% European, 8% other) completed approximately 30 electronic daily life assessments over 10 days regarding their current location, affect, activities, and current and desired social context., Results: Solitude was common; 86% of solitude instances happened by individuals' own choosing. When desiring solitude, older adults were more likely to be at home and less likely to be outdoors, compared to other locations. Middle-aged adults showed no such solitude-location associations. Among middle-aged adults, desire for solitude was associated with decreased positive affect. Older adults experienced no such dip in affect., Discussion: Findings suggest that compared to middle-aged adults, older adults are more likely to go to locations that match their desired social context, and also that solitude-seeking has more positive ramifications for older adults. Findings are discussed in the context of age differences in activities, social preferences, and emotion regulation., (© The Author(s) 2018. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Being alone is often equated with loneliness. Yet, recent findings suggest that the objective state of being alone (i.e. solitude) can have both positive and negative connotations. The present research aimed to examine (1) affective experience in daily solitude; and (2) the association between everyday affect in solitude and well-being. We examined the distinct roles of culture and immigration in moderating these associations. Method: Using up to 35 daily life assessments of momentary affect, solitude, and emotional well-being in two samples (Canada and China), the study compared older adults who aged in place (local Caucasians in Vancouver , Canada and local Hong Kong Chinese in Hong Kong, China) and older adults of different cultural heritages who immigrated to Canada (immigrated Caucasians and immigrated East Asians). Results: We found that older adults of East Asian heritage experienced more positive and less negative affect when alone than did Caucasians. Reporting positive affect in solitude was more positively associated with well-being in older adults who had immigrated to Canada as compared to those who had aged in place. Conclusions: These findings speak to the unique effects of culture and immigration on the affective correlates of solitude and their associations with well-being in old age.

Objective: Solitude is a ubiquitous experience, often confused with loneliness, yet sometimes sought out in daily life. This study aimed to identify distinct types of solitude experiences from everyday affect/thought patterns and to examine how and for whom solitude is experienced positively versus negatively., Method: One hundred community-dwelling adults aged 50-85 years (64% female; 56% East Asian, 36% European, 8% other/mixed heritage) and 50 students aged 18-28 years (92% female; 42% East Asian, 22% European, 36% other/mixed) each completed approximately 30 daily life assessments over 10 days on their current and desired social situation, thoughts, and affect., Results: Multilevel latent profile analysis identified two types of everyday solitude: one characterized by negative affect and effortful thought (negative solitude experiences) and one characterized by calm and the near absence of negative affect/effortful thought (positive solitude experiences). Individual differences in social self-efficacy and desire for solitude were associated with everyday positive solitude propensity; trait self-rumination and self-reflection were associated with everyday negative solitude propensity., Conclusions: This study provides a new framework for conceptualizing everyday solitude. It identifies specific affect/thought patterns that characterize distinct solitude experience clusters, and it links these clusters with well-established individual differences. We discuss key traits associated with thriving in solitude., (© 2018 Wiley Periodicals, Inc.)

Aging takes place in a social context but older adults also spend a significant amount of their time alone. Solitude (the objective state of being alone and without social interaction) has been associated with negative experiences but also with specific benefits. We examine the importance of social relationships for time-varying associations between affective experiences and solitude. Using repeated daily life assessments from an adult life span sample (Study 1, N = 183, age: 20-81 years) and an older adult sample (Study 2, N = 97, age: 50-85 years), we examined the moderating role of social relationship quality on within-person solitude-affect associations. Data were analyzed using multilevel models controlling for gender, age, overall amount of time in solitude, retirement status, marital status, education, and current work activity. Higher relationship quality was associated with higher average affective well-being. Compared to being with others, participants reported lower levels of high-arousal positive affect (PA) during solitude in both studies. In Study 1, solitude was also associated with higher levels of low-arousal negative affect (NA) and higher levels of low-arousal PA compared to when with others. Across both studies, individuals with higher quality relationships reported lesser increases in low-arousal NA when in solitude, as compared to individuals with lower quality relationships. Findings highlight that solitude is experienced less negatively for individuals embedded in a context of higher quality social relationships. Thus, preservation and promotion of social resources in older adulthood may be important to ward off potential negative ramifications of spending a significant amount of time alone. (PsycINFO Database Record, ((c) 2018 APA, all rights reserved).)

Objective: Although research often relies on retrospective affect self-reports, little is known about personality's role in retrospective reports and how these converge or deviate from affect reported in the moment. This micro-longitudinal study examines personality (Neuroticism, Extraversion) and emotional salience (peak and recent affect) associations with retrospective-momentary affect report discrepancies over different time frames., Method: Participants were 179 adults aged 20-78 (M = 48.7 years; 73.7% Caucasian/White) who each provided up to 60 concurrent affect reports over 10 days, then retrospectively reported overall intensity of each affective state after 1 day and again after 1-2 months., Results: Multilevel models revealed that individuals retrospectively overreported or underreported various affective states, exhibiting peak associations for high arousal positive and negative affect, recency associations for low arousal positive affect, and distinct personality profiles that strengthened over time. Individuals high in both Extraversion and Neuroticism exaggerated high arousal positive and negative affect and underreported low arousal positive affect, high Extraversion/low Neuroticism individuals exaggerated high arousal positive affect and underreported low arousal positive affect, and low Extraversion/high Neuroticism individuals exaggerated high and low arousal negative affect., Conclusions: This study is the first to identify arousal-specific retrospective affect report discrepancies over time and suggests retrospective reports also reflect personality differences in affective self-knowledge., (© 2016 Wiley Periodicals, Inc.)

Background: Spending time alone constitutes a ubiquitous part of our everyday lives. As we get older, alone time increases. Less is known, however, about age differences in the experience of spending time alone (momentary solitude)., Objectives: We examined time-varying associations between momentary solitude, affect quality, and two hypothalamic-pituitary-adrenal axis activity markers [salivary cortisol; dehydroepiandrosterone sulfate (DHEAs)] to better understand the affective and biological correlates of momentary solitude across the adult life span., Method: A total of 185 adults aged 20-81 years (mean age = 49 years, 51% female, 74% Caucasian) completed questionnaires on momentary solitude (alone vs. not alone) and current affect on a handheld device, and provided concurrent saliva samples up to seven times a day for 10 consecutive days. Data were analyzed using multilevel models, controlling for the overall amount of time participants spent alone during the study (overall solitude)., Results: Greater overall solitude was associated with decreased average high arousal positive affect and increased average cortisol and DHEAs levels. Momentary solitude was associated with reduced high arousal positive affect, increased low arousal positive affect, and increased low arousal negative affect. Age by momentary solitude interactions indicate that greater age was associated with increased high arousal positive affect and reduced low arousal negative affect during momentary solitude. Furthermore, momentary solitude was associated with increased cortisol and DHEAs. With greater age, the association between momentary solitude and cortisol weakened., Conclusion: Consistent with the negative connotations to loneliness and objective social isolation, greater overall solitude was associated with negative affective and biological correlates. Spending a large overall amount of time alone in old age might thus have negative ramifications for health and well-being. Momentary solitude, in contrast, can be a double-edged sword as evidenced by both positive and negative well-being implications. Importantly, greater age is linked to more favorable affective and biological correlates of momentary solitude. The momentary state of spending time alone is thus an experience that is not necessarily negative and that may improve with aging., (© 2016 S. Karger AG, Basel.)

Objective: Marriage partners exert a special influence on each other's health and wellbeing, potentially even more so in old age, when social networks shrink and spouses become ever more important resources for dealing with everyday problems. This study extends past research by examining associations between spousal levels of neuroticism, a key trait tied to wellbeing and health, and everyday fluctuations in positive affect (PA) and negative affect (NA), physical symptoms, and responses to everyday problems., Methods: Forty-nine wives and 49 husbands aged 60-83 years (M marriage duration = 42.5 years) provided independent neuroticism self-reports. Spouses then simultaneously reported their PA and NA, physical health symptoms, and everyday problems 3 times daily for 9 days (up to 27 daily life assessments in total) using handheld computers., Results: Hierarchical linear models replicate past research by linking higher individual neuroticism with lower overall PA, higher overall NA, and more severe overall physical symptoms. Interestingly, although individual neuroticism did not affect associations between everyday problems and affect and physical symptoms, spousal neuroticism did moderate these relationships. Individuals with spouses higher in neuroticism (compared with those with spouses lower in neuroticism) reported less pronounced elevations in NA and physical symptoms, and less pronounced reductions in PA, when number of problems was greater, even when controlling for partner presence and various individual- and couple-level covariates., Conclusions: Findings are discussed in the context of evolutionary psychology and suggest that spousal neuroticism may serve adaptive functions by increasing vigilance and preparing older spouses to deal with everyday problems.

As nanoparticles (NPs) are cleared via phagocytes of the mononuclear phagocyte system (MPS), we hypothesized that the function of circulating monocytes and dendritic cells (MO/DC) in blood can predict NP clearance (CL). We measured MO/DC phagocytosis and reactive oxygen species (ROS) production in mice, rats, dogs, and patients with refractory solid tumors. Pharmacokinetic studies of polyethylene glycol (PEG)-encapsulated liposomal doxorubicin (PEGylated liposomal doxirubicin [PLD]), CKD-602 (S-CKD602), and cisplatin (SPI-077) were performed at the maximum tolerated dose. MO/DC function was also evaluated in patients with recurrent epithelial ovarian cancer (EOC) administered PLD. Across species, a positive association was observed between cell function and CL of PEGylated liposomes. In patients with EOC, associations were observed between PLD CL and phagocytosis (R(2) = 0.43, P = 0.04) and ROS production (R(2) = 0.61, P = 0.008) in blood MO/DC. These findings suggest that probes of MPS function may help predict PEGylated liposome CL across species and PLD CL in patients with EOC.

Background: Increased susceptibility of smokers to ambient PM may potentially promote development of COPD and accelerate already present disease., Objectives: To characterize the acute and subacute lung function response and inflammatory effects of controlled chamber exposure to concentrated ambient fine particles (CAFP) with MMAD  ≤  2.5 microns in ex-smokers and lifetime smokers., Methods: Eleven subjects, aged 35-74 years, came to the laboratory 5 times; a training day and two exposure days separated by at least 3 weeks, each with a post-exposure visit 22 h later. Double-blind and counterbalanced exposures to "clean air" (mean 1.5 ± 0.6 μg/m3) or CAFP (mean 108.7 ± 24.8 μg/m3 ) lasted 2 h with subjects at rest., Results: At 3 h post-exposure subjects' DTPA clearance half-time significantly increased by 6.3 min per 100 μg/m3 of CAFP relative to "clean air". At 22 h post-exposure they showed significant reduction of 4.3% per 100 μg/m3 in FEV1 and a significant DLCO decrease by 11.1% per 100 μg/m3 of CAFP relative to "clean air". At both 3 h and 22 h the HDL cholesterol level significantly decreased by 4.5% and 4.1%, respectively. Other blood chemistries and markers of lung injury, inflammation and procoagulant activity were within the normal range of values at any condition., Conclusions: The results suggest that an acute 2 h resting exposure of smokers and ex-smokers to fine ambient particulate matter may transiently affect pulmonary function (spirometry and DLCO) and increase DTPA clearance half-time. Except for a post exposure decrease in HDL no other markers of pulmonary inflammation, prothrombotic activity and lung injury were significantly affected under the conditions of exposure.

Epidemiologic studies suggest that dietary vitamin E is an important candidate intervention for asthma. Our group has shown that daily consumption of vitamin E (γ-tocopherol, γT) has anti-inflammatory actions in both rodent and human phase I studies. The objective of this study was to test whether γT supplementation could mitigate a model of neutrophilic airway inflammation in rats and in healthy human volunteers. F344/N rats were randomized to oral gavage with γT versus placebo, followed by intranasal LPS (20μg) challenge. Bronchoalveolar lavage fluid and lung histology were used to assess airway neutrophil recruitment. In a phase IIa clinical study, 13 nonasthmatic subjects completed a double-blinded, placebo-controlled crossover study in which they consumed either a γT-enriched capsule or a sunflower oil placebo capsule. After 7 days of daily supplementation, they underwent an inhaled LPS challenge. Induced sputum was assessed for neutrophils 6 h after inhaled LPS. The effect of γT compared to placebo on airway neutrophils post-LPS was compared using a repeated-measures analysis of variance. In rats, oral γT supplementation significantly reduced tissue infiltration (p<0.05) and accumulation of airway neutrophils (p<0.05) that are elicited by intranasal LPS challenge compared to control rats. In human volunteers, γT treatment significantly decreased induced sputum neutrophils (p=0.03) compared to placebo. Oral supplementation with γT reduced airway neutrophil recruitment in both rat and human models of inhaled LPS challenge. These results suggest that γT is a potential therapeutic candidate for prevention or treatment of neutrophilic airway inflammation in diseased populations., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Elevated inflammation and altered immune responses are features found in atopic asthmatic airways. Recent studies indicate γ-tocopherol (GT) supplementation can suppress airway inflammation in allergic asthma. We studied the effects of in vitro GT supplementation on receptor-mediated phagocytosis and expression of cell surface molecules associated with innate and adaptive immunity on sputum-derived macrophages. Cells from nonsmoking healthy (n = 6) and mild house dust mite-sensitive allergic asthmatics (n = 6) were treated ex vivo with GT (300 µM) or saline (control). Phagocytosis of opsonized zymosan A bioparticles (Saccharomyces cerevisiae) and expression of surface molecules associated with innate and adaptive immunity were assessed using flow cytometry. GT caused significantly decreased (p < 0.05) internalization of attached zymosan bioparticles and decreased (p < 0.05) macrophage expression of CD206, CD36 and CD86 in allergic asthmatics but not in controls. Overall, GT caused downregulation of both innate and adaptive immune response elements, and atopic status appears to be an important factor., (Copyright © 2013 S. Karger AG, Basel.)

Background: Exposure to ozone activates innate immune function and causes neutrophilic (PMN) airway inflammation that in some individuals is robustly elevated. The interplay between immuno-inflammatory function and genomic signaling in those with heightened inflammatory responsiveness to ozone is not well understood., Objectives: Determine baseline predictors and post exposure discriminators for the immuno-inflammatory response to ozone in inflammatory responsive adult volunteers., Methods: Sputum induction was performed on 27 individuals before and after a two hour chamber exposure to 0.4 ppm ozone. Subjects were classified as inflammatory responders or non-responders to ozone based on their PMN response. Innate immune function, inflammatory cell and cytokine modulation and transcriptional signaling pathways were measured in sputum., Results: Post exposure, responders showed activated innate immune function (CD16: 31,004 MFI vs 8988 MFI; CD11b: 44,986 MFI vs 24,770 MFI; CD80: 2236 MFI vs 1506 MFI; IL-8: 37,603 pg/ml vs 2828 pg/ml; and IL-1β: 1380 pg/ml vs 318 pg/ml) with muted signaling of immune cell trafficking pathways. In contrast, non-responders displayed decreased innate immune activity (CD16, CD80; phagocytosis: 2 particles/PMN vs 4 particles/PMN) post exposure that was accompanied by a heightened signaling of immune cell trafficking pathways., Conclusions: Inflammatory responsive and non responsive individuals to ozone show an inverse relationship between immune cell trafficking and immuno-inflammatory functional responses to ozone. These distinct genomic signatures may further our understanding about ozone-induced morbidity in individuals with different levels of inflammatory responsiveness.

Background: Atopic asthmatic patients are reported to be more sensitive to the effects of environmental endotoxin (LPS) than healthy volunteers (HVs). It is unknown whether this sensitivity is due to dysregulated inflammatory responses after LPS exposure in atopic asthmatic patients., Objective: We sought to test the hypothesis that atopic asthmatic patients respond differentially to inhaled LPS challenge compared with HVs., Methods: Thirteen allergic asthmatic (AA) patients and 18 nonallergic nonasthmatic subjects (healthy volunteers [HVs]) underwent an inhalation challenge to 20,000 endotoxin units of Clinical Center Reference Endotoxin (LPS). Induced sputum and peripheral blood were obtained at baseline and 6 hours after inhaled LPS challenge. Sputum and blood samples were assayed for changes in inflammatory cell numbers and cytokine and cell-surface marker levels on monocytes and macrophages., Results: The percentage of neutrophils in sputum (%PMN) in induced sputum similarly and significantly increased in both HVs and AA patients after inhaled LPS challenge. However, the absolute numbers of leukocytes and PMNs recruited to the airways were significantly lower in AA patients compared with those seen in HVs with inhaled LPS challenge. Sputum levels of IL-6 and TNF-α were significantly increased in both cohorts, but levels of IL-1β and IL-18 were only significantly increased in the HV group. Cell-surface expression of Toll-like receptors 4 and 2 were significantly enhanced only in the HV group., Conclusions: The airway inflammatory response to inhaled LPS challenge is blunted in AA patients compared with that seen in HVs and accompanied by reductions in airway neutrophilia and inflammasome-dependent cytokine production. These factors might contribute to increased susceptibility to airway microbial infection or colonization in AA patients., (Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Background: The evaluation of sputum leukocytes by flow cytometry (FCM) is an opportunity to assess characteristics of cells residing in the central airways, yet it is hampered by certain inherent properties of sputum including mucus and large amounts of contaminating cells and debris., Objective: To develop a gating strategy based on specific antibody panels in combination with light scatter properties for flow cytometric evaluation of sputum cells., Methods: Healthy and mild asthmatic volunteers underwent sputum induction. Manually selected mucus "plug" material was treated with dithiothreitol, filtered and total leukocytes acquired. Multicolor FCM was performed using specific gating strategies based on light scatter properties, differential expression of CD45 and cell lineage markers to discriminate leukocytes from squamous epithelial cells and debris., Results: The combination of forward scatter and CD45 expression reliably segregated sputum leukocytes from contaminating squamous epithelial cells and debris. Overlap of major leukocyte populations (neutrophils, macrophages/monocytes) required the use of specific antibodies (e.g. CD16, CD64, CD14, HLA-DR) that differentiated granulocytes from monocytes and macrophages. These gating strategies allowed identification of small populations of eosinophils, CD11c+ myeloid dendritic cells, B-cells and natural killer cells., Conclusions: Multicolor FCM can be successfully applied to sputum samples to identify and characterize leukocyte populations residing on the surfaces of the central airways., Clinical Relevance: This research describes detailed methods to overcome difficulties associated with FCM of sputum samples, which previously has been lacking in the literature. FCM of sputum samples can provide valuable information on inflammation and immunological response elements in the bronchial airways for both clinical diagnostic and research applications and can be a useful tool in inhalation toxicology for assessing health effects of inhaled environmental pollutants.

Rationale: Exposure to ozone causes a decrease in spirometric lung function and an increase in airway inflammation in healthy young adults at concentrations as low as 0.08 ppm, close to the National Ambient Air Quality Standard for ground level ozone., Objectives: To test whether airway effects occur below the current ozone standard and if they are more pronounced in potentially susceptible individuals, such as those deficient in the antioxidant gene glutathione S-transferase mu 1 (GSTM1)., Methods: Pulmonary function and subjective symptoms were measured in 59 healthy young adults (19-35 yr) immediately before and after exposure to 0.0 (clean air, CA) and 0.06 ppm ozone for 6.6 hours in a chamber while undergoing intermittent moderate exercise. The polymorphonuclear neutrophil (PMN) influx was measured in 24 subjects 16 to 18 hours postexposure., Measurements and Main Results: Subjects experienced a significantly greater (P = 0.008) change in FEV(1) (± SE) immediately after exposure to 0.06 ppm ozone compared with CA (-1.71 ± 0.50% vs. -0.002 ± 0.46%). The decrement in FVC was also greater (P = 0.02) after ozone versus CA (-2.32 ± 0.41% vs. -1.13 ± 0.34%). Similarly, changes in %PMN were greater after ozone (54.0 ± 4.6%) than CA (38.3 ± 3.7%) exposure (P < 0.001). Symptom scores were not different between ozone versus CA. There were no significant differences in changes in FEV(1), FVC, and %PMN between subjects with GSTM1-positive and GSTM1-null genotypes., Conclusions: Exposure of healthy young adults to 0.06 ppm ozone for 6.6 hours causes a significant decrement of FEV(1) and an increase in neutrophilic inflammation in the airways. GSTM1 genotype alone appears to have no significant role in modifying the effects.

Background: Asthma is a known risk factor for acute ozone-associated respiratory disease. Ozone causes an immediate decrease in lung function and increased airway inflammation. The role of atopy and asthma in modulation of ozone-induced inflammation has not been determined., Objective: We sought to determine whether atopic status modulates ozone response phenotypes in human subjects., Methods: Fifty volunteers (25 healthy volunteers, 14 atopic nonasthmatic subjects, and 11 atopic asthmatic subjects not requiring maintenance therapy) underwent a 0.4-ppm ozone exposure protocol. Ozone response was determined based on changes in lung function and induced sputum composition, including airway inflammatory cell concentration, cell-surface markers, and cytokine and hyaluronic acid concentrations., Results: All cohorts experienced similar decreases in lung function after ozone. Atopic and atopic asthmatic subjects had increased sputum neutrophil numbers and IL-8 levels after ozone exposure; values did not significantly change in healthy volunteers. After ozone exposure, atopic asthmatic subjects had significantly increased sputum IL-6 and IL-1beta levels and airway macrophage Toll-like receptor 4, Fc(epsilon)RI, and CD23 expression; values in healthy volunteers and atopic nonasthmatic subjects showed no significant change. Atopic asthmatic subjects had significantly decreased IL-10 levels at baseline compared with healthy volunteers; IL-10 levels did not significantly change in any group with ozone. All groups had similar levels of hyaluronic acid at baseline, with increased levels after ozone exposure in atopic and atopic asthmatic subjects., Conclusion: Atopic asthmatic subjects have increased airway inflammatory responses to ozone. Increased Toll-like receptor 4 expression suggests a potential pathway through which ozone generates the inflammatory response in allergic asthmatic subjects but not in atopic subjects without asthma., (Published by Mosby, Inc.)

Ozone and lipopolysaccharide (LPS) are environmental pollutants with adverse health effects noted in both healthy and asthmatic individuals. The authors and others have shown that inhalation of ozone and LPS both induce airway neutrophilia. Based on these similarities, the authors tested the hypothesis that common biological factors determine response to these two different agents. Fifteen healthy, nonasthmatic volunteers underwent a 0.4 part per million ozone exposure for 2 h while performing intermittent moderate exercise. These same subjects underwent an inhaled LPS challenge with 20,000 LPS units of Clinical Center Reference LPS, with a minimum of 1 month separating these two challenge sessions. Induced sputum was obtained 24 h before and 4-6 h after each exposure session. Sputum was assessed for total and differential cell counts and expression of cell surface proteins as measured by flow cytometry. Sputum supernatants were assayed for cytokine concentration. Both ozone and LPS challenge augmented sputum neutrophils and subjects' responses were significantly correlated (R = .73) with each other. Ozone had greater overall influence on cell surface proteins by modifying both monocytes (CD14, human leukocyte antigen [HLA]-DR, CD11b) and macrophages (CD11b, HLA-DR) versus LPS where CD14 and HLA-DR were modified only on monocytes. However, LPS significantly increased interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha, with no significant increases seen after ozone challenge. Ozone and LPS exposure in healthy volunteers induce similar neutrophil responses in the airways; however, downstream activation of innate immune responses differ, suggesting that oxidant versus bacterial air pollutants may be mediated by different mechanisms.

The effects of low-level ozone exposure (0.08 ppm) on pulmonary function in healthy young adults are well known; however, much less is known about the inflammatory and immunomodulatory effects of low-level ozone in the airways. Techniques such as induced sputum and flow cytometry make it possible to examine airways inflammatory responses and changes in immune cell surface phenotypes following low-level ozone exposure. The purpose of this study was to determine if exposure to 0.08 parts per million ozone for 6.6 h induces inflammation and modifies immune cell surface phenotypes in the airways of healthy adult subjects. Fifteen normal volunteers underwent an established 0.08 part per million ozone exposure protocol to characterize the effect of ozone on airways inflammation and immune cell surface phenotypes. Induced sputum and flow cytometry were used to assess these endpoints 24 h before and 18 h after exposure. The results showed that exposure to 0.08 ppm ozone for 6.6 h induced increased airway neutrophils, monocytes, and dendritic cells and modified the expression of CD14, HLA-DR, CD80, and CD86 on monocytes 18 h following exposure. Exposure to 0.08 parts per million ozone is associated with increased airways inflammation and promotion of antigen-presenting cell phenotypes 18 hours following exposure. These findings need to be replicated in a similar experiment that includes a control air exposure.

Background: The glutathione-S-transferase Mu 1 (GSTM1) null genotype has been reported to be a risk factor for acute respiratory disease associated with increases in ambient air ozone levels. Ozone is known to cause an immediate decrease in lung function and increased airway inflammation. However, it is not known whether GSTM1 modulates these ozone responses in vivo in human subjects., Objective: The purpose of this study was to determine whether the GSTM1 null genotype modulates ozone responses in human subjects., Methods: Thirty-five healthy volunteers were genotyped for the GSTM1 null mutation and underwent a standard ozone exposure protocol to determine whether lung function and inflammatory responses to ozone were different between the 19 GSTM1 wild type and 16 GSTM1 null volunteers., Results: GSTM1 did not modulate lung function responses to acute ozone. Granulocyte influx 4 hours after challenge was similar between GSTM1 normal and null volunteers. However, GSTM1 null volunteers had significantly increased airway neutrophils 24 hours after challenge, as well as increased expression of HLA-DR on airway macrophages and dendritic cells., Conclusion: The GSTM1 null genotype is associated with increased airways inflammation 24 hours after ozone exposure, which is consistent with the lag time observed between increased ambient air ozone exposure and exacerbations of lung disease.

Background: The uptake of inhaled particulate matter by airway phagocytes is an important defence mechanism contributing to the clearance of potentially toxic substances, including aeroallergens, from the lung. Since airway monocytes and macrophages can also function as antigen presenting cells, their ability to engulf materials deposited on the airway surface is of particular interest in patients with allergic asthma. To determine whether airway mononuclear phagocytes of patients with allergic asthma might have enhanced phagocytic activity, the in vivo uptake of inhaled radiolabelled particles was compared in 10 patients with mild allergic asthma and 8 healthy (non-allergic) individuals., Methods: Phagocyte function was assessed by quantifying the proportion of radioactivity associated with cellular and supernatant fractions of induced sputum 2 h after inhalation of radiolabelled sulfur colloid particles. All subjects were pretreated with albuterol before sputum induction. A standardised breathing pattern was used to target aerosol deposition in the bronchial airways., Results: In vivo particle uptake by airway cells was significantly greater in patients with asthma than in healthy volunteers (57.2% (95% CI 46.5% to 67.9%) vs 22.3% (95% CI 4.9% to 39.6%), p<0.01), as was in vitro phagocytosis of opsonised zymosan-A bioparticles. There was also a significant correlation (r = 0.85, p<0.01) between the percentage of sputum mononuclear phagocytes and the percentage uptake of particles in the patients with asthma but not in the control subjects., Conclusions: In vivo particle uptake by airway macrophages is enhanced in persons with mild asthma. Enhanced uptake and processing of particulate antigens could contribute to the pathogenesis and progression of allergic airways disease and may contribute to the increased risk of disease exacerbation associated with particulate exposure.

Background: Ozone exposure induces airway neutrophilia and modifies innate immune monocytic cell-surface phenotypes in healthy individuals. High-dose inhaled corticosteroids can reduce O(3)-induced airway inflammation, but their effect on innate immune activation is unknown., Objectives: We used a human O(3) inhalation challenge model to examine the effectiveness of clinically relevant doses of inhaled corticosteroids on airway inflammation and markers of innate immune activation in healthy volunteers., Methods: Seventeen O(3)-responsive subjects [>10% increase in the percentage of polymorphonuclear leukocytes (PMNs) in sputum, PMNs per milligram vs. baseline sputum] received placebo, or either a single therapeutic dose (0.5 mg) or a high dose (2 mg) of inhaled fluticasone proprionate (FP) 1 hr before a 3-hr O(3) challenge (0.25 ppm) on three separate occasions at least 2 weeks apart. Lung function, exhaled nitric oxide, sputum, and systemic biomarkers were assessed 1-5 hr after the O(3) challenge. To determine the effect of FP on cellular function, we assessed sputum cells from seven subjects by flow cytometry for cell-surface marker activation., Results: FP had no effect on O(3)-induced lung function decline. Compared with placebo, 0.5 mg and 2 mg FP reduced O(3)-induced sputum neutrophilia by 18% and 35%, respectively. A similar effect was observed on the airway-specific serum biomarker Clara cell protein 16 (CCP16). Furthermore, FP pretreatment significantly reduced O(3)-induced modification of CD11b, mCD14, CD64, CD16, HLA-DR, and CD86 on sputum monocytes in a dose-dependent manner., Conclusions: This study confirmed and extended data demonstrating the protective effect of FP against O(3)-induced airway inflammation and immune cell activation.

Background: Environmental exposure to endotoxin is a known cause of exacerbation of asthma. Inhaled endotoxin protocols have been used to evaluate airway cell surface phenotypes associated with antigen presentation and innate immunity in healthy volunteers, but not in allergic volunteers., Objectives: To establish the safety of challenge with low-dose endotoxin (10,000 endotoxin units) (lipopolysaccharide [LPS]) inhalation in allergic individuals, to measure airway cell surface phenotypes associated with antigen presentation and innate immunity in induced sputum (IS) after LPS challenge, and to conduct gene expression profiling in IS cells to determine which host genetic networks are modified by LPS inhalation., Methods: Induced sputum was obtained before and 6 hours after LPS inhalation in 10 allergic volunteers (8 with asthma and 2 with rhinitis). Flow cytometry was used to examine cell surface phenotypes on IS cells. Genomic expression was analyzed on a subset of IS samples (n = 10) using microarray and ingenuity pathway analysis., Results: A total of 10,000 endotoxin units of LPS induced significant up-regulation of membrane CD14, CD11b, CD16, HLA-DR, CD86, and Fcepsilon receptor 1 on sputum phagocytes and increased expression of genes that influence antigen-presenting surface molecules (HLA-DR, chemokine ligand 2 or monocyte chemoattractant protein 1, v-rel reticuloendotheliosis viral oncogene homolog, prostaglandin-endoperoxide synthase 2 or cyclooxygenase 2, and transforming growth factor beta), immune activation (CD14, interleukin 1beta, and regulated upon activation, normal T cell expressed and secreted), and inflammation (intracellular adhesion molecule 1 and inhibitory kappaBalpha). Gene profiles for nuclear factor kappaB, interleukin 1, and tumor necrosis factor pathways were also significantly affected., Conclusions: Low-dose inhaled endotoxin challenge is safe in allergic individuals with mild to moderate disease. It enhances airway cell surface phenotypes and expression of genes associated with antigen presentation, innate immunity, and inflammation. Microarray with ingenuity pathway analysis can be successfully applied to sputum cells to characterize genetic responses to inhaled exacerbants.

Although smallpox vaccine-associated myopericarditis has been reported, the risk of cardiac ischemic events remains uncertain. We identified personnel receiving the smallpox vaccination and compared them to a historical referent population. The rate of cardiac ischemia diagnoses in the 30 days following smallpox vaccination was 140.1 per 100,000 person-years, compared to 143.5 per 100,000 person-years in referent group (RR 1.0 [95% CI: 0.7-1.4]). The rate of cardiac ischemic events in vaccinees was 121.4 per 100,000 person-years before and 175.7 after adopting pre-vaccination cardiac screening (RR 1.4 [95% CI: 0.8-2.7]). Implementation of pre-vaccination cardiac risk factor screening was not associated with a reduction in cardiac events.

Background: In vitro, endotoxin on coarse fraction particulate matter (PM2.5-10) accounts for the majority of the ability of PM2.5-10 to induce cytokine responses from alveolar macrophages., Objective: We examined in vivo whether inhaled PM2.5-10 from local ambient air induce inflammatory and immune responses in the airways of healthy human beings and whether biologic material on PM2.5-10 accounts for these effects., Methods: On 3 separate visits, 9 healthy subjects inhaled nebulized saline (0.9%, control), PM2.5-10 collected from local ambient air that was heated to inactivate biological material (PM2.5-10-), or nonheated PM (PM2.5-10+). PM2.5-10 deposition (approximately 0.65 mg/subject) targeted the bronchial airways (confirmed by using radiolabeled aerosol), and induced sputum was obtained 2 to 3 hours postinhalation for analysis of cellular and biochemical markers of inflammation and innate immune function., Results: Inhaled PM2.5-10+ induced elevated inflammation (% PMNs, macrophage mRNA TNF-alpha), increased eotaxin, upregulated immune surface phenotypes on macrophages (mCD14, CD11b, HLA-DR), and increased phagocytosis (monocytes) versus saline (P < .05). Biological inactivation of PM2.5-10 (PM2.5-10-) had no effect on neutrophilia but significantly (P < .05) attenuated mRNA TNF-alpha, eotaxin levels, cell surface marker responses, and phagocytosis., Conclusion: Biological components of PM2.5-10 are not necessary to induce neutrophil responses but are essential in mediating macrophage responses. The ability of PM2.5-10 to activate monocytic cells and potentially skew the airways toward an allergic phenotype by enhancing eotaxin levels may enhance responses to allergens or bacteria in individuals with allergy., Clinical Implications: PM2.5-10 might enhance the response of individuals with allergy to airborne bacteria.

We combined two techniques, radiolabeled aerosol inhalation delivery and induced sputum, to examine in vivo the time course of particle uptake by airway macrophages in 10 healthy volunteers. On three separate visits, induced sputum was obtained 40, 100, and 160 min after inhalation of radiolabeled sulfur colloid (SC) aerosol (Tc99 m-SC, 0.2 microm colloid size delivered in 6-microm droplets). On a fourth visit (control) with no SC inhalation, induced sputum was obtained and SC particles were incubated (37 degrees C) in vitro with sputum cells for 40, 100, and 160 min (matching the times associated with in vivo sampling). Total and differential cell counts were recorded for each sputum sample. Compared with 40 min (6 +/- 3%), uptake in vivo was significantly elevated at 100 (31 +/- 5%) and 160 min (27 +/- 4%); both were strongly associated with the number of airway macrophages (R = 0.8 and 0.7, respectively); and the number and proportion of macrophages at 40 min were significantly (P < 0.05) elevated compared with control (1,248 +/- 256 versus 555 +/- 114 cells/mg; 76 +/- 6% versus 60 +/- 5%). Uptake in vitro increased in a linear fashion over time and was maximal at 160 min (40 min, 12 +/- 2%; 100 min, 16 +/- 4%; 160 min, 24 +/- 6%). These data suggest that airway surface macrophages in healthy subjects rapidly engulf insoluble particles. Further, macrophage recruitment and phagocytosis-modifying agents are factors in vivo that likely affect particle uptake and its time course.

Background: We have been studying the innate immune response of airways cells of healthy human volunteers to inhaled LPS, a Toll-like receptor 4 (TLR4) ligand, and have shown that macrophage phagocytic capacity is blunted., Objective: Because a primary feature of dendritic cell (DC) maturation is a loss of phagocytic capacity, we sought to determine whether acute LPS inhalation in healthy volunteers promotes DC maturation in vivo., Methods: Phagocytosis (IgG-opsonized zymosan particles) and cell-surface phenotypes were analyzed by flow cytometry of induced sputum cells obtained before and 6 hours after Clinical Center Reference Endotoxin (CCRE; 20,000 EU) inhalation in 9 healthy volunteers., Results: Neutrophils were elevated in the airways after CCRE inhalation (67% +/- 6% vs 37% +/- 6%; P < .05). Phagocytosis (monocytes, macrophages) was blunted (73%, 46%; P < .05) and negatively correlated with PMN influx ( R = -0.73; P < .05) after CCRE inhalation. GM-CSF and IL-1beta, potent DC maturation agents, were elevated after versus before CCRE inhalation (217 pg/mL +/- 103 pg/mL vs 722 pg/mL +/- 202 pg/mL; 83 pg/mL +/- 24 pg/mL vs 148 pg/mL +/- 37 pg/mL, respectively; P < .05). Markers of DC maturation (CD80, CD86, HLA-DR) were upregulated on monocytes and macrophages ( P < .05), and discrete populations of mature DC were observed ( P < .05) after CCRE inhalation., Conclusion: Inhaled LPS, directly through TLR4 stimulation of immature DC and/or indirectly through stimulation of GM-CSF and IL-1beta, induces pulmonary DC maturation in vivo . Inhaled LPS may enhance allergic airways responses to air pollution through its ability to induce DC maturation.

Background: We previously reported that inhalation of 5 mug of endotoxin (30,000 endotoxin units [EU]) induced airway neutrophilia and decreased phagocytosis by airway monocytes, macrophages, and neutrophils. Conversely, we recently reported that very low doses of endotoxin, which are not associated with neutrophil influx, enhance response to allergen in the nasal and bronchial airway., Objective: We sought to determine whether endotoxin (0-10,000 EU) at doses that do not induce airway neutrophilia prime airway phagocyte function, alter expression of relevant cell-surface receptors (membrane-bound CD14 [mCD14] and CD11b/CR3), and cause induction of a T(H)2 cytokine profile in the airway., Methods: Thirteen nonallergic healthy volunteers were challenged on separate occasions with escalating doses of Clinical Center Reference Endotoxin (CCRE; 0, 2500, 5000, and 10,000 EU), with 9 volunteers completing the entire dose range. Sputum cells and fluid-phase components were recovered 6 hours after challenge. Sputum inflammatory cells were analyzed by means of flow cytometry for mCD14 and CD11b expression and immune function (phagocytosis of IgG-opsonized zymosan particles)., Results: At all doses of CCRE, there was no increase in airway neutrophils relative to that caused by saline. However, inhalation of 10,000 EU enhanced phagocytosis (monocytes and macrophages), upregulated expression of CD11b and mCD14 (monocytes and neutrophils), and increased IL-13 levels, whereas IFN-gamma levels were significantly decreased., Conclusion: The 10,000-EU dose of CCRE is subthreshold for inducing airway neutrophilia but primes phagocyte function and cell-surface receptor expression in the presence of increased IL-13 and decreased IFN-gamma levels. We speculate that low-dose endotoxin challenge skews airway inflammation in a T(H)2 direction in vivo .

Active surveillance for laboratory-confirmed Yersinia enterocolitica (YE) infections was conducted at 5 Foodborne Diseases Active Surveillance Network (FoodNet) sites in the United States during 1996-1999. The annual incidence averaged 0.9 cases/100,000 population. After adjusting for missing data, the average annual incidence by race/ethnicity was 3.2 cases/100,000 population among black persons, 1.5 cases/100,000 population among Asian persons, 0.6 cases/100,000 population among Hispanic persons, and 0.4 cases/100,000 population among white persons. Incidence increased with decreasing age in all race/ethnicity groups. Black infants had the highest incidence (141.9 cases/100,000 population; range, 8.7 cases/100,000 population in Minnesota to 207.0 cases/100,000 population in Georgia). Seasonal variations in incidence, with a marked peak in December, were noted only among black persons. YE infections should be suspected in black children with gastroenteritis, particularly during November-February. Culturing for YE should be part of routine testing of stool specimens by clinical laboratories serving populations at risk, especially during the winter months.

We used a gamma camera to monitor the retention and clearance of radiolabeled human serum albumin (HSA), a water-soluble material with molecular weight of 66,000 Daltons, and radiolabeled sulfur colloid (SC), an insoluble submicron (0.22 microm) particle, following localized deposition in a 4-5-mm bronchus in each of five dogs. The average retention time of HSA was significantly greater than that of SC both in the deposition site (23.3 +/- 2.3 vs. 18.2 +/- 2.9 min respectively, p < 0.05) and in the clearance pathway (26.5 +/- 2.0 vs. 22.0 +/- 1.4 min, respectively, p < 0.05). The mean percent retention at the deposition site at 60 minutes post-deposition also was significantly greater for HSA than for SC (33.5 +/- 10.1 vs. 11.6 +/- 4.7%, respectively, p < 0.05). The percentage of HSA which had cleared to the level of the cuffed endotracheal tube was significantly less than that of SC (18.0 +/- 6.7 vs. 35.8 +/- 3.5%, respectively, p < 0.05) at 60 min post-deposition. These findings indicate that a low-permeating water-soluble material such as HSA deposited on the surface of an airway remains in contact with the sensitive airway epithelium to a greater extent than does a solid insoluble particle. Based on our results, we speculate that the slower clearance of HSA compared to SC was likely due to diffusion of a greater portion of the HSA into the periciliary sol layer which may be transported less efficiently than the mucus layer during mucociliary clearance. Additionally, some degree of uptake of HSA by bronchial epithelium may have contributed to its increased retention.

Pulmonary inflammation secondary to oxidant generation catalyzed by transition metals associated with inhaled particles is one factor postulated to underlie the acute health effects of particulate air pollution. We postulated that inhaled iron oxide particles with associated amounts of soluble iron should induce mild pulmonary inflammation and lead to altered alveolar epithelial integrity and altered gas exchange. To test this hypothesis we examined the effects of inhaled iron oxide particles on alveolar epithelial permeability. Sixteen healthy subjects inhaled aerosols of iron oxide particles (1.5 microm mass median aerodynamic diameter) having either high or low water-soluble iron content [3.26 +/- 0.25 (SE) and 0.14 +/- 0.04 microg soluble iron/mg of particles, respectively] for 30 min at an average mass concentration of 12.7 mg/m(3). Alveolar epithelial permeability was assessed by measuring the pulmonary clearance of an inhaled radiolabeled tracer molecule ((99m)Tc-DTPA, diethylene triamine pentaacetic acid) using a gamma camera at 1/2 h and 24 h post particle exposure. Carbon monoxide lung diffusing capacity (DL(CO)) and spirometry were also performed before and after breathing the iron oxide. As a control, on a separate day, the procedures were duplicated except that the subject breathed particle-free air. For those subjects breathing aerosols with high soluble iron, we found no significant difference in DTPA clearance half-times after breathing particles versus particle-free air either at 1/2 h (97.4 +/- 15.4 vs. 116.1 +/- 15.5 min, respectively) or 24 h postinhalation (105.1 +/- 13.8 vs. 106.9 +/- 12.9 min, respectively). Likewise, for those subjects breathing aerosols with low soluble iron content we found no significant difference in DTPA clearance half-times after breathing particles versus particle-free air either at 1/2 h (108.6 +/- 31.9 vs. 95.6 +/- 10.8 min, respectively) or 24 h postinhalation (130.0 +/- 18.0 vs. 105.8 +/- 13.7 min, respectively). We found no significant differences in DL(CO) between particle exposures and air exposures. Minor differences in spirometric measurements were noted but were not statistically significant. We conclude that inhalation of iron oxide particles did not cause an appreciable alteration of alveolar epithelial permeability, lung diffusing capacity, or pulmonary function in healthy subjects under the studied conditions.

Bronchoalveolar lavage (BAL) was used to sample lung cells and biochemical components in the lung air spaces at various times from 1 to 91 d after intrapulmonary instillation of 2.6 microm-diameter iron oxide particles in human subjects. The instillation of particles induced transient acute inflammation during the first day post instillation (PI), characterized by increased numbers of neutrophils and alveolar macrophages as well as increased amounts of protein, lactate dehydrogenase, and interleukin-8 in BAL fluids. This response was subclinical and was resolved within 4 d PI. A similar dose-dependent response was seen in rats 1 d after intratracheal instillation of the same particles. The particles contained small amounts of soluble iron (240 ng/mg) and possessed the capacity to catalyze oxidant generation in vitro. Our findings indicate that the acute inflammation after particle exposure may, at least partially, be the result of oxidant generation catalyzed by the presence of residual amounts of ferric ion, ferric hydroxides, or oxyhydroxides associated with the particles. These findings may have relevance to the acute health effects associated with increased levels of ambient particulate air pollutants.

Bronchoalveolar lavage (BAL) was used to sample retention of particles within the alveolar macrophage (AM) compartment at various times from 1 to 91 d following intrapulmonary instillation of 2. 6-microm-diameter iron oxide (Fe2O3) particles in human subjects. Particles were cleared from the lavagable AM compartment in a biphasic pattern, with a rapid-phase clearance half-time of 0.5 d and long-term clearance half-time of 110 d, comparable to retention kinetics determined by more traditional methods. The intracellular distribution of particles within lavaged AMs was similar in bronchial and alveolar BAL fractions. AMs with high intracellular particle burdens disappeared from the lavagable phagocytic AM population disproportionately more rapidly (shorter clearance half-time) than did AMs with lower particle burdens, consistent with the occurrence of a particle redistribution phenomenon as previously described in similar studies in rats. The rates of AM disappearance from the various particle burden categories was generally slightly slower in bronchial fractions than in alveolar fractions. The instillation of particles induced a transient acute inflammatory response at 24 h postinstillation (PI), characterized by increased numbers of neutrophils and alveolar macrophages in BAL fluids. This response was subclinical and was resolved within 4 d PI.

The atmosphere constitutes a prime vehicle for the movement and redistribution of metals. Metal exposure can be associated with an oxidative stress. We tested the hypothesis that, in response to an iron-containing particle, the human respiratory tract will demonstrate an increased expression of both lactoferrin and ferritin as the host attempts to transport and store the metal in a chemically less-reactive form and therefore diminish the oxidative stress the particle presents. Subjects (n = 22) were instilled with 20 ml of saline and 20 ml of an iron-containing particle suspended in saline in a right middle lobe bronchus and a lingular bronchus, respectively. At either 1, 2, or 4 days after this exposure, the volunteer was lavaged for a sample of the lower respiratory tract, and concentrations of L-ferritin, transferrin, and lactoferrin were measured by enzyme immunoassay, immunoprecipitin analysis, and enzyme-linked immunosorbent assay (ELISA), respectively. Transferrin receptor was also quantified by ELISA. The concentrations of L-ferritin in the lavage fluid of lung exposed to particles were significantly increased relative to the levels of the protein in the segment exposed to saline. Relative to saline instillation, transferrin was significantly diminished after exposure to the iron-containing particle, whereas both lactoferrin and transferrin receptor concentrations in the segment of the lung exposed to the particle were significantly elevated. We conclude that instillation of an iron-containing particle was associated with a disequilibrium in iron metabolism in the lower respiratory tract. The response included increased ferritin and lactoferrin concentrations, whereas transferrin concentrations diminished. This coordinated series of reactions by the host effects a decrease in the availability of catalytically reactive iron to likely diminish the consequent oxidative stress to the human host.

Recent studies have challenged the generally accepted hypothesis that bronchial particle clearance is complete within 24-48 h postdeposition. We studied bronchial retention of inert particles using a bronchoscope and microspray nozzle to localize deposition in a bronchus while avoiding alveolar deposition. Six-microliter aliquots (444 kBq) of submicrometer (number mean diameter = 0.22 microns, geometric standard deviation = 1.75) technetium-99m-labeled (99mTc) sulfur colloid (SC) particles (n = 6) or the unbound radiolabel 99mTc-pertechnetate (99mTcO4-; n = 3) were sprayed onto a 5-mm-diam bronchus in halothane-anesthetized dogs. Radioactivity at the deposition site and clearance pathway was monitored externally with a gamma camera beginning immediately postspray. Bronchial retention of SC was 8.5 +/- 2.4 and 1.5 +/- 0.7% at 3 and 24 h postspray, respectively. Tracheal mucus velocity was measured at 10.4 +/- 2.2 mm/min. For comparison, clearance of inhaled submicrometer SC particles was also measured in the same dogs. Retention of inhaled aerosolized SC (peripheral lung deposition) was 98.1 +/- 1.1 and 76.3 +/- 1.8% at 3 and 24 h, respectively. 99mTcO4- cleared from the bronchi slightly more rapidly than did SC. Radioactivity was readily detected in the blood after deposition of 99mTcO4- but not of SC. Thus SC cleared by mucociliary transport, whereas 99mTcO4- cleared predominantly by transepithelial absorption. We conclude that clearance of submicrometer particles from a 5-mm conducting airway is very nearly complete by 24 h, with approximately 92% of the clearance occurring within the first 3 h postdeposition.

A 3-year-old Quarter Horse gelding admitted for evaluation of weight loss, signs of depression, and dermatitis of the coronary bands was found to have eosinophilic gastroenteritis. Intralesional nematodes identified as Strongylus edentatus were seen in multiple microscopic sections of the small colon, suggesting a parasitic cause of the disease.

A condition resembling human sclerosing encapsulating peritonitis was identified in 3 young large-breed dogs. All 3 dogs had similar clinical signs: ascites, vomiting, and excessive borborygmus. The condition was discovered at laparotomy and confirmed histologically. Laparotomy revealed a sac-like formation totally or partially occupying the peritoneal cavity. The predominant histologic abnormality was marked peritoneal and serosal fibrosis. None of the dogs had a favorable response to treatment, and euthanasia was performed because of development of abdominal distention.