Cuneyt M. Alper

Emotional Style and Susceptibility to the Common Cold

Objective: It has been hypothesized that people who typically report experiencing negative emotions are at greater risk for disease and those who typically report positive emotions are at less risk. We tested these hypotheses for host resistance to the common cold. Methods: Three hundred thirty‐four healthy volunteers aged 18 to 54 years were assessed for their tendency to experience positive emotions such as happy, pleased, and relaxed; and for negative emotions such as anxious, hostile, and depressed. Subsequently, they were given nasal drops containing one of two rhinoviruses and monitored in quarantine for the development of a common cold (illness in the presence of verified infection). Results: For both viruses, increased positive emotional style (PES) was associated (in a dose‐response manner) with lower risk of developing a cold. This relationship was maintained after controlling for prechallenge virus‐specific antibody, virus‐type, age, sex, education, race, body mass, and season (adjusted relative risk comparing lowest‐to‐highest tertile = 2.9). Negative emotional style (NES) was not associated with colds and the association of positive style and colds was independent of negative style. Although PES was associated with lower levels of endocrine hormones and better health practices, these differences could not account for different risks for illness. In separate analyses, NES was associated with reporting more unfounded (independent of objective markers of disease) symptoms, and PES with reporting fewer. Conclusions: 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.

Sleep Habits and Susceptibility to the Common Cold

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 A total of 153 healthy men and women (age range, 21-55 years) volunteered to participate in the study. For 14 consecutive days, they reported their sleep duration and sleep efficiency (percentage 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 quarantined, administered nasal drops containing a rhinovirus, and monitored for the development of a clinical cold (infection in the presence of objective signs of illness) on the day before and for 5 days after exposure. RESULTS There was a graded association with average sleep duration: participants with less than 7 hours of sleep were 2.94 times (95% confidence interval [CI], 1.18-7.30) more likely to develop a cold than those with 8 hours or more of sleep. The association with sleep efficiency was also graded: participants with less than 92% efficiency were 5.50 times (95% CI, 2.08-14.48) more likely to develop a cold than those with 98% or more efficiency. These relationships could not be explained by differences in prechallenge virus-specific antibody titers, demographics, season of the year, body mass, socioeconomic status, psychological variables, or health practices. The percentage of days feeling rested was not associated with colds. CONCLUSION Poorer sleep efficiency and shorter sleep duration in the weeks preceding exposure to a rhinovirus were associated with lower resistance to illness.

Objective and Subjective Socioeconomic Status and Susceptibility to the Common Cold

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.

Positive Emotional Style Predicts Resistance to Illness After Experimental Exposure to Rhinovirus or Influenza A Virus

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 = 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. BMI = body mass index; CI = confidence interval; NES = negative emotional style; PES = positive emotional style; RV = rhinovirus; TCID = Tissue Culture Infectious Dose.

Sociability and Susceptibility to the Common Cold

There is considerable evidence that social relationships can influence health, but only limited evidence on the health effects of the personality characteristics that are thought to mold peoples social lives. We asked whether sociability predicts resistance to infectious disease and whether this relationship is attributable to the quality and quantity of social interactions and relationships. Three hundred thirty-four volunteers completed questionnaires assessing their sociability, social networks, and social supports, and six evening interviews assessing daily interactions. They were subsequently exposed to a virus that causes a common cold and monitored to see who developed verifiable illness. Increased sociability was associated in a linear fashion with a decreased probability of developing a cold. Although sociability was associated with more and higher-quality social interactions, it predicted disease susceptibility independently of these variables. The association between sociability and disease was also independent of baseline immunity (virus-specific antibody), demographics, emotional styles, stress hormones, and health practices.

Temporal Relationships Between Colds, Upper Respiratory Viruses Detected by Polymerase Chain Reaction, and Otitis Media in Young Children Followed Through a Typical Cold Season

INTRODUCTION. Otitis media is a frequent complication of a viral upper respiratory tract infection, and the reported co-incidence of those diseases increases with assay sensitivity and sampling density. We determined the incidence of otitis-media complications in young children when referenced to cold-like illnesses and to concurrent virus recovery from the nasopharynx. METHODS. A total of 60 children from 24 families were followed from October 2003 through April 30, 2004, by daily parental recording of illness signs, weekly pneumatic otoscopic examinations, and periodic polymerase chain reaction assay of collected nasal fluids for common viruses. RESULTS. One hundred ninety-nine cold-like illnesses were observed, but a sample for virus assay was not collected concurrent with 71 episodes. Of the remainder, 73% of cold-like illnesses were temporally related to recovery of 1 or a combination of the assayed viruses, with rhinovirus predominating. For non–cold-like illness periods, 54 (18%) of 297 assays were positive for virus, and the virus frequency distribution was similar to that for cold-like illnesses. There were 93 diagnosed otitis-media episodes; 65 (70%) of these occurred during a cold-like illness. For the 79 otitis-media episodes with available nasal samples, 61 (77%) were associated with a positive virus result. In this population, the otitis-media complication rate for a cold-like illness was 33%. CONCLUSIONS. A cold-like illness was not a prerequisite for polymerase chain reaction detection of viruses in the nose and nasopharynx of young children. Viral detection by polymerase chain reaction in the absence of a cold-like illness is associated with complications in some subjects. Otitis media is a complication of viral infection both with and without concurrent cold-like illnesses, thus downwardly biasing coincidence estimates that use cold-based illnesses as the denominator.

Magnetic resonance imaging of the development of otitis media with effusion caused by functional obstruction of the Eustachian tube

In this study, magnetic resonance imaging (MRI) was used to define in vivo the effect of experimental functional obstruction of the eustachian tube (ET) on vascular permeability and the development of middle ear (ME) effusion. After collection of baseline data for ME pressure and MRI, the right tensor veli palatini muscle of 10 cynomolgus monkeys was injected with botulinum toxin A to induce ET obstruction. The left tensor veli palatini muscle was injected with saline in 4 monkeys. Right and left ME pressures and compliances were measured twice daily over a follow-up period of 36 days, and MRI scanning sessions including administration of a contrast agent, gadopentetate dimeglumine, were repeated on days 3, 6, 11, 15, 21,29, and 36 in 6 animals and on days 15, 21, 29, and 36 in 4 animals. Two right ears did not develop underpressures, 5 developed persistent underpressures, and 3 developed underpressures that resolved. No changes in MRI parameters were noted for the ears that did not develop underpressures, but a progressive brightening of the ME on T2-weighted images, indicative of the development of inflammation and effusion, was noted for the others. Also, an increasing rate of transfer of the contrast agent between the vascular and ME compartments, indicative of increasing vascular permeability, was observed to track the temporal changes in ME pressure. These results support a causal relationship between ET dysfunction, ME underpressures, increased vascular permeability, and otitis media with effusion.

Effect of Rimantadine Treatment on Clinical Manifestations and Otologic Complications in Adults Experimentally Infected with Influenza A (H1N1) Virus

Susceptible adults (n = 105) were enrolled into a randomized double-blind study of rimantadine treatment of experimental influenza A infection. Subjects were cloistered for 8 days and challenged with a rimantadine-sensitive strain of influenza A H1N1 virus at the end of the first day. Forty-eight hours after challenge and for 8 days, 54 subjects received placebo and 51 received rimantadine (100 mg orally, twice a day). Symptoms, signs, and pathophysiologies were monitored. Nine subjects were not infected. Seventeen subjects (38%) in the rimantadine and 26 (53%) in the placebo group became ill. A beneficial effect of rimantadine was documented for virus shedding, symptom load, and sinus pain. Rimantadine had no effect on nasal patency, mucociliary clearance, nasal signs, or on symptoms and signs of otologic complications. These results do not support a preventive effect of rimantadine on the development of otologic manifestations of influenza A infection in adults.

Upregulation of messenger RNA for inflammatory cytokines in middle ear mucosa in a rat model of acute otitis media.

A rat model for acute otitis media has been established and was used to delineate the temporal expression of messenger RNA for key inflammatory cytokines. Inoculation with live Streptococcus pneumoniae induced a rapid expression of tumor necrosis factor α (within 6 hours) followed by upregulation of message for interleukin (IL)–6 (peak at 12 to 24 hours, remaining elevated through 120 hours) and IL-10 (peak at 24 hours). Inducible nitric oxide synthase message was also selectively increased following live bacterial inoculation (peak at 12 to 24 hours). Although there was a detectable inflammatory response to killed bacteria, it was minimal, was of short duration, and preceded the peak for live bacteria; only expression of IL-6 was significantly increased in this group (peak at 12 hours, remaining elevated through 72 hours). We interpret this to be due to an inflammatory response to bacterial products (such as lipopolysaccharide) in the heat-killed bacterial inoculum. The phosphate-buffered saline (PBS)–inoculated group exhibited a transient increase of IL-6 message, which indicates that this cytokine is a sensitive marker of the acute response to trauma. Otherwise, PBS invoked only a slight reaction in the mucosa with respect to the other inflammatory mediators being measured.

Cytokine Profiles in a Rat Model of Otitis Media With Effusion Caused by Eustachian Tube Obstruction With and Without Streptococcus pneumoniae Infection

Objective Cytokine expression was studied in a rat model of otitis media with effusion.