We propose a model wherein chronic stress results in glucocorticoid receptor resistance (GCR) that, in turn, results in failure to downregulate inflammatory response. Here we test the model in two viral-challenge studies. In study 1, we assessed stressful life events, GCR, and control variables including baseline antibody to the challenge virus, age, body mass index (BMI), season, race, sex, education, and virus type in 276 healthy adult volunteers. The volunteers were subsequently quarantined, exposed to one of two rhinoviruses, and followed for 5 d with nasal washes for viral isolation and assessment of signs/symptoms of a common cold. In study 2, we assessed the same control variables and GCR in 79 subjects who were subsequently exposed to a rhinovirus and monitored at baseline and for 5 d after viral challenge for the production of local (in nasal secretions) proinflammatory cytokines (IL-1β, TNF-α, and IL-6). Study 1: After covarying the control variables, those with recent exposure to a long-term threatening stressful experience demonstrated GCR; and those with GCR were at higher risk of subsequently developing a cold. Study 2: With the same controls used in study 1, greater GCR predicted the production of more local proinflammatory cytokines among infected subjects. These data provide support for a model suggesting that prolonged stressors result in GCR, which, in turn, interferes with appropriate regulation of inflammation. Because inflammation plays an important role in the onset and progression of a wide range of diseases, this model may have broad implications for understanding the role of stress in health.lymphocytes | receptor sensitivity | psychological stress | cortisol | hypothalamic-pituitary-adrenocortical axis

Summary Acute respiratory infections (ARI) are a common reason for seeking medical attention and the threat of pandemic influenza will likely add to these numbers. Using human viral challenge studies with live rhinovirus, respiratory syncytial virus, and influenza A, we developed peripheral blood gene expression signatures that distinguish individuals with symptomatic ARI from uninfected individuals with > 95% accuracy. We validated this “acute respiratory viral” signature - encompassing genes with a known role in host defense against viral infections - across each viral challenge. We also validated the signature in an independently acquired dataset for influenza A and classified infected individuals from healthy controls with 100% accuracy. In the same dataset, we could also distinguish viral from bacterial ARIs (93% accuracy). These results demonstrate that ARIs induce changes in human peripheral blood gene expression that can be used to diagnose a viral etiology of respiratory infection and triage symptomatic individuals.

Background Sleep quality is thought to be an important predictor of immunity and in turn susceptibility to the common cold. This article examines whether sleep duration and efficiency in the weeks preceding viral exposure are associated with cold susceptibility. Methods Participants were 153 healthy men and women volunteers, ages 21–55. For 14 consecutive days, they reported their sleep duration and sleep efficiency (percent of time in bed actually asleep) for the previous night, and whether they felt rested. Average scores for each sleep variable were calculated over the 14-day baseline. Subsequently, participants were administered nasal drops containing a rhinovirus, quarantined and monitored on the day before and for five days following exposure for development of a clinical cold (infection in the presence of objective signs of illness). Results There was a graded association with average sleep duration, with those with <7 hours sleep 2.94 times (CI[95%]=1.18–7.30) more likely to develop a cold than those with ≥ 8 hours. The association with sleep efficiency was also graded with those with < 92% efficiency 5.50 times (CI[95%]=2.08–14.48) more likely to develop a cold than those with efficiencies ≥98%. These relations could not be explained by differences in pre-challenge virus-specific antibody, demographics, season of the year, body mass, socioeconomic status, psychological variables or health practices. Percent of days feeling rested was not associated with colds. Conclusions Poorer sleep efficiency and shorter sleep duration in the weeks preceding an exposure to a rhinovirus were associated with lower resistance to illness.

The tendency to experience positive emotions was associated with greater resistance to objectively verifiable colds. PES was also associated with reporting fewer unfounded symptoms and NES with reporting more.

Exhaled breath condensate (EBC) pH is low in several lung diseases and it normalises with therapy.The current study examined factors relevant to EBC pH monitoring. Intraday and intraweek variability were studied in 76 subjects. The pH of EBC collected orally and from isolated lower airways was compared in an additional 32 subjects. Effects of ventilatory pattern (hyperventilation/hypoventilation), airway obstruction after methacholine, temperature (-44 to z13uC) and duration of collection (2-7 min), and duration of sample storage (up to 2 yrs) were examined. All samples were collected with a disposable condensing device, and de-aerated with argon until pH measurement stabilised.Mean EBC pH (n=76 subjects, total samples=741) was 7.7¡0.49 (mean¡SD). Mean intraweek and intraday coefficients of variation were 4.5% and 3.5%. Control of EBC pH appears to be at the level of the lower airway. Temperature of collection, duration of collection and storage, acute airway obstruction, subject age, saliva pH, and profound hyperventilation and hypoventilation had no effect on EBC pH.The current authors conclude that in health, exhaled breath condensate pH is slightly alkaline, held in a narrow range, and is controlled by lower airway source fluid. Measurement of exhaled breath condensate pH is a simple, robust, reproducible and relevant marker of disease. Eur Respir J 2003; 22: 889-894.

Objective:We ask whether subjective socioeconomic status (SES) predicts who develops a common cold when exposed to a cold virus. Design: 193 healthy men and women ages 21-55 years were assessed for subjective (perceived rank) and objective SES, cognitive, affective and social dispositions, and health practices. Subsequently, they were exposed by nasal drops to a rhinovirus or influenza virus and monitored in quarantine for objective signs of illness and self-reported symptoms. Main Outcome Measures: Infection, signs and symptoms of the common cold, and clinical illness (infection and significant objective signs of illness). Results: Increased subjective SES was associated with decreased risk for developing a cold for both viruses. This association was independent of objective SES and of cognitive, affective and social disposition that might provide alternative spurious (third factor) explanations for the association. Poorer sleep among those with lesser subjective SES may partly mediate the association between subjective SES and colds. Conclusions: Increased Subjective SES is associated with less susceptibility to upper respiratory infection, and this association is independent of objective SES, suggesting the importance of perceived relative rank to health.

Objective: In an earlier study, positive emotional style (PES) was associated with resistance to the common cold and a bias to underreport (relative to objective disease markers) symptom severity. This work did not control for social and cognitive factors closely associated with PES. We replicate the original study using a different virus and controls for these alternative explanations. Methods: One hundred ninety-three healthy volunteers ages 21 to 55 years were assessed for a PES characterized by being happy, lively, and calm; a negative emotional style (NES) characterized by being anxious, hostile, and depressed; other cognitive and social dispositions; and self-reported health. Subsequently, they were exposed by nasal drops to a rhinovirus or influenza virus and monitored in quarantine for objective signs of illness and self-reported symptoms. Results: For both viruses, increased PES was associated with lower risk of developing an upper respiratory illness as defined by objective criteria (adjusted odds ratio comparing lowest with highest tertile ϭ 2.9) and with reporting fewer symptoms than expected from concurrent objective markers of illness. These associations were independent of prechallenge virus-specific antibody, virus type, age, sex, education, race, body mass, season, and NES. They were also independent of optimism, extraversion, mastery, self-esteem, purpose, and self-reported health. Conclusions: We replicated the prospective association of PES and colds and PES and biased symptom reporting, extended those results to infection with an influenza virus, and "ruled out" alternative hypotheses. These results indicate that PES may play a more important role in health than previously thought.

Prophylactic administration of fluconazole to the VLBW infant for the first 28 days of life is safe and results in a decreased risk of rectal colonization by candidal species. Larger studies to determine the effect of prophylaxis on candidal septicemia and development of resistance in such a selective high-risk group are warranted before initiation of routine prophylaxis.fluconazole, very low birth weight infant, prophylaxis, candidal sepsis, sensitivities to fluconazole.