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Experimental experience suggests that microbial agents including probiotics and prebiotics (representative microbial agents) play a critical role in defending against respiratory virus infection. We aim to systematically examine these agents' effect on respiratory viral infection and encourage research into clinical applications. An electronic literature search was conducted from published data with a combination of a microbial agents search component containing synonyms for microbial agents-related terms and a customized search component for respiratory virus infection. Hazard ratio (HR), risk ratio (RR) and standard deviation (SD) were employed as effect estimates. In 45 preclinical studies, the mortality rates decreased in the respiratory viral infection models that included prebiotics or prebiotics as interventions (HR: 0.70; 95% confidence interval (CI): 0.56-0.87; P=0.002). There was a significant decrease in viral load due to improved gut microbiota (SD: -1.22; 95% CI: -1.50 to -0.94; P<0.001). Concentrations of interferon (IFN)-α (SD: 1.05; 95% CI: 0.33-1.77; P=0.004), IFN-γ (SD: 0.83; 95% CI: 0.01-1.65; P=0.05) and interleukin (IL)-12 (SD: 2.42; 95% CI: 0.32-4.52; P=0.02), IL-1β (SD: 0.01; 95% CI: -0.37 to 0.40; P=0.94) increased, whereas those of TNF-α (SD: -0.58; 95% CI: -1.59 to 0.43; P=0.26) and IL-6 (SD: -0.59; 95% CI: -1.24 to 0.07; P=0.08) decreased. Six clinical studies had lower symptom scores (SD: -0.09; 95% CI: -0.44 to 0.26; P=0.61) and less incidence of infection (RR: 0.80; 95% CI: 0.64-1.01; P=0.06). Our research indicates that probiotics and prebiotics pose a defensive possibility on respiratory viral infection and may encourage the clinical application., (© 2021 The Author(s).)

Objective: For the majority of people with acute sore throat, over-the-counter treatments represent the primary option for symptomatic relief. This study evaluated the in vitro bactericidal activity of lozenges containing the antiseptic hexylresorcinol against five bacteria associated with acute sore throat: Staphylococcus aureus, Streptococcus pyogenes, Moraxella catarrhalis, Haemophilus influenzae and Fusobacterium necrophorum., Results: Hexylresorcinol 2.4 mg lozenges were dissolved into 5 mL of artificial saliva medium. Inoculum cultures were prepared in triplicate for each test organism to give an approximate population of 10 8 colony-forming units (cfu)/mL. Bactericidal activity was measured by log reduction in cfu. Greater than 3log 10 reductions in cfu were observed at 1 min after dissolved hexylresorcinol lozenges were added to S. aureus (log 10 reduction cfu/mL ± standard deviation, 3.3 ± 0.2), M. catarrhalis (4.7 ± 0.4), H. influenzae (5.8 ± 0.4) and F. necrophorum (4.5 ± 0.2) and by 5 min for S. pyogenes (4.3 ± 0.4). Hexylresorcinol lozenges achieved a > 99.9% reduction in cfu against all tested organisms within 5 min, which is consistent with the duration for a lozenge to dissolve in the mouth. In conclusion, in vitro data indicate that hexylresorcinol lozenges offer rapid bactericidal activity against organisms implicated in acute sore throat.

Avibacterium paragallinarum is the causative agent of infectious coryza, a highly contagious respiratory disease in chickens. Given its fastidious nature, this bacterium is difficult to recover and identify, particularly from locations colonized by normal bacterial flora. Standard PCR methods have been utilized for detection but are labor-intensive and not feasible for high-throughput testing. We evaluated a real-time PCR (rtPCR) method targeting the HPG-2 region of A. paragallinarum , and validated a high-throughput extraction for this assay. Using single-tube extraction, the rtPCR detected 4 A. paragallinarum (ATCC 29545 T and 3 clinical) isolates with a limit of detection (LOD) of 10 cfu/mL and a PCR efficiency of 89-111%. Cross-reaction was not detected with 33 non- A. paragallinarum , all close relatives from the family Pasteurellaceae . Real-time PCR testing on extracts of 66 clinical samples (choana, sinus, or trachea) yielded 98.2% (35 of 36 on positives, 30 of 30 on negatives) agreement with conventional PCR. Duplicate samples tested in a 96-well format extraction in parallel with the single-tube method produced equivalent LOD on all A. paragallinarum isolates, and 96.8% agreement on 93 additional clinical samples extracted with both procedures. This A. paragallinarum rtPCR can be utilized for outbreak investigations and routine monitoring of susceptible flocks.

Background: Patients  with  viral respiratory infections/viral rhinitis/common colds are often treated with antibiotic; however, there is little information on whether or how bacterial microbiota in the nose and nasopharynx might influence the course of viral illnesses., Methods: To initiate investigation of possible interaction between viral respiratory illness and microbiota of the nose/nasopharynx, we used microarray technology to examine 100 nasal lavage fluid (NLF) samples for bacterial species and recorded the bacterial titer of culturable bacteria. Rhinovirus illnesses were induced by self-inoculation using the "finger to nose or eye natural transmission route" in 10 otherwise healthy young adults. NLF samples were collected during wellness and at specific time points following experimental rhinovirus inoculation., Results: The rhinovirus infection rate was 70%. There were no consistent changes in the prevalence of different bacterial species determined by microarray and bacterial titer by culture methods during rhinovirus infection. The bacterial profile in NLF samples showed high variability between volunteers but low variability in multiple NLFs obtained before and following infection from the same volunteer. Streptococcus epidermidis/coagulase-negative staphylococcus (CNS) were identified in all 10 subjects. One or more bacterial sinus/otitis pathogens were identified by microarray in 6 of the 10 volunteers. The microarray identified a few bacteria not included in traditional bacterial cultures., Conclusion: Our pilot study showed that each of the 10 volunteers had a unique bacterial profile in the nose by microarray analysis and that bacterial load did not change during experimental rhinovirus colds. Larger scale studies are warranted., (© 2013 The Authors. International Forum of Allergy & Rhinology published by Wiley Periodicals, Inc., on behalf of ARS-AAOA, LLC.)

Cytokines are a group of diverse molecules that influence the function of every organ system. They are most well studied in their effects on the immune system and their integral role in mediating inflammation. The common cold and otitis media are two such disease states, and much has been learned about the various effects of cytokines in each disease. Most often the viruses isolated include rhinovirus (RV), respiratory syncytial virus (RSV), adenovirus, coronavirus, and picornavirus. Otitis media, sinusitis, bronchiolitis, pneumonia, and asthma exacerbation are commonly accepted as complications of viral upper respiratory tract infections. Furthermore, otitis media and upper respiratory infections are inextricably linked in that the majority (>70 %) of cases of acute otitis media occur as complications of the common cold. Cytokine polymorphisms have been associated with the severity of colds as well as the frequency of otitis media. This article attempts to update the reader on various studies that have recently been published regarding the role of cytokines in these two disease entities.

Bacterial 'colonisation' of the nasopharynx by potential bacterial pathogens is frequent in early childhood and is frequent as part of a dynamic process in which the microbiota of the oral and nasopharynx are established. New understanding recognizes this process is evolving and that competition and likely regulation occurs among potential pathogens as well as between pathogens and commensals. Such events elicit host responses that either results in clearance or persistence within the nasal and oral pharynx. Environmental factors such as recent antibiotic usage, smoking and vaccines all impact on the success of specific bacterial species in this competition. Understanding the significant bacterial interactions as well as how bacteria work in concert to regulate density, expression of virulence factors and capacity to produce disease are likely to provide new approaches to disease prevention., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Pathogenic bacteria have been cultured from the osteomeatal complex (OMC) in one-third of adults with apparent acute bacterial sinusitis; however, it is not known whether bacteria are present in the OMC during uncomplicated viral colds in adults., Methods: Adult volunteers were recruited for a study during wellness and at the time of acute common cold. Swab cultures were obtained from the OMC and from the nasopharynx by 2 routes (through the nose and through the mouth). Swab eluates were inoculated on selective agars to detect S. pneumoniae, H. influenzae, and M. catarrhalis., Results: Bacterial pathogens were detected in the OMC more frequently during common colds than during wellness (31% vs 8%, p < 0.008). Pathogens detected in the OMC were always present in the nasopharynx of the subject., Conclusion: Bacterial pathogens are present in the OMC in a subgroup of adult patients with uncomplicated upper respiratory illness/common cold. The nasopharynx appears to be the reservoir for bacterial pathogens in the OMC., (Copyright © 2011 American Rhinologic Society-American Academy of Otolaryngic Allergy, LLC.)

Health education can offer a valuable window onto conceptual and behavioral change. In Study 1, we mapped out 3rd-grade Chinese children's beliefs about causes of colds and flu and ways they can be prevented. We also explored older adults' beliefs as a possible source of the children's ideas. In Study 2, we gave 3rd- and 4th-grade Chinese children either a conventional cold/flu education program or an experimental "Think Biology" program that focused on a biological causal mechanism for cold/flu transmission. The "Think Biology" program led children to reason about cold/flu causation and prevention more scientifically than the conventional program, and their reasoning abilities dovetailed with their mastery of the causal mechanism. Study 3, a modified replication of Study 2, found useful behavioral change as well as conceptual change among children who received the "Think Biology" program and documented coherence among knowledge enrichment, conceptual change, and behavioral change.

The objective of this study was to investigate the possibility of visualizing the ability of hydroxypropylmethylcellulose (HPMC) and a nasal spray (First Defense), in which the bioadhesive is HPMC, to bind to human mucosal cells using inorganic (black carbon particles and Congo red dye) and organic markers (Escherichia coli). A significant reduction in the bacterial adhesiveness has been observed. Our findings indicate the possibility of counteracting the lock-and-key mechanism of microorganism adhesion using the bioadhesive properties of polymers, such as HPMC, in First Defense to prevent a possible contact between adhesins and complementary receptors.

Background: Staphylococcus aureus is among the most important pathogens in today's hospital setting., Methods: The effects of sneezing on the airborne dispersal of S. aureus and other bacteria were assessed in 11 healthy nasal S. aureus carriers with experimentally induced rhinovirus colds. Airborne dispersal was studied by volumetric air sampling in 2 chamber sessions with and without histamine-induced sneezing. After 2 days of preexposure measurements, volunteers were inoculated with a rhinovirus and monitored for 14 days. Daily quantitative nasal- and skin-culture samples for bacteria and nasal-culture samples for rhinovirus were obtained, cold symptoms were assessed, and volunteer activities were recorded during sessions., Results: All participants developed a cold. Sneezing caused a 4.7-fold increase in the airborne dispersal of S. aureus, a 1.4-fold increase in coagulase-negative staphylococci (CoNS), and a 3.9-fold increase in other bacteria (P < .001). An additional 2.83 colony forming units (cfu) of S. aureus/m3/min, 3.24 cfu of CoNS/m3/min, and 474.61 cfu of other bacteria/m3/min were released per sneeze. Rhinovirus exposure did not change the frequency of sneezing or airborne dispersal. Having respiratory allergies increased the spread of S. aureus by 3.8-fold during sneezing sessions (P < .001)., Conclusion: Nasal S. aureus carriers disperse a significant amount of S. aureus into the air by sneezing. Experimental colds do not alter bacterial dispersal, but respiratory allergies multiply the effect of dispersing S. aureus.

Objective: To determine whether healthy adult nasal carriers of Staphylococcus aureus can disperse S. aureus into the air after rhinovirus infection., Design: We investigated the "cloud" phenomenon among adult nasal carriers of S. aureus experimentally infected with a rhinovirus. Eleven volunteers were studied for 16 days in an airtight chamber wearing street clothes, sterile garb, or sterile garb plus surgical mask; rhinovirus inoculation occurred on day 2. Daily quantitative air, nasal, and skin cultures for S. aureus; cold symptom assessment; and nasal rhinovirus cultures were performed., Setting: Wake Forest University School of Medicine, Winston-Salem, North Carolina., Participants: Wake Forest University undergraduate or graduate students who had persistent nasal carriage of S. aureus for 4 or 8 weeks., Results: After rhinovirus inoculation, dispersal of S. aureus into the air increased 2-fold with peak increases up to 34-fold. Independent predictors of S. aureus dispersal included the time period after rhinovirus infection and wearing street clothes (P < .05). Wearing barrier garb but not a mask decreased dispersal of S. aureus into the air (P < .05)., Conclusion: Virus-induced dispersal of S. aureus into the air may have an important role in the transmission of S. aureus and other bacteria.

The cross-protection and haemagglutination-inhibition antibodies present in chickens vaccinated with one of the nine currently recognized Kume haemagglutinin serovars of Haemophilus paragallinarum were investigated. The results confirmed the widely accepted dogma that serogroups A, B, and C represent three distinct immunovars. Within Kume serogroup A, there was generally good cross-protection among all four serovars. However, within Kume serogroup C, there was evidence of a reduced level of cross-protection between some of the four serovars. The haemagglutination-inhibition antibody levels generally showed the same trend as with the cross-protection results. This study suggests that some apparent field failures of infectious coryza vaccines may be due to a lack of cross-protection between the vaccine strains and the field strains. Our results will help guide the selection of strains for inclusion in infectious coryza vaccines.

Objective: To evaluate the effect of uncomplicated viral respiratory infections (colds) on middle ear pressure in healthy school-aged children., Methods: Children (ages 2-12) with normal tympanograms before onset of illness had bilateral tympanometry daily except weekends for 2 weeks after the onset of a cold. Nasopharyngeal secretion obtained at onset of illness was cultured for bacterial pathogens of otitis media using selective agars and tested for rhinovirus, coronavirus, respiratory syncytial virus, influenza A and B, and parainfluenza 1-3 by reverse transcriptase polymerase chain reaction technology. Tympanometry was designated as abnormal with peak pressure of < or =-100 daPa or > or =50 daPa and/or a compliance peak of < 0.2 cm(3)., Results: Eighty-six colds were studied, 82 in schoolchildren (5-12 years old) and 4 in 2- to 3-year-olds. Abnormal negative middle ear pressure occurred at least once during the 2 weeks after onset in 57 (66%) of the 86 colds. Tympanometry was abnormal in the first week after onset in 50 (88%) of the 57 colds and was abnormal on a single day in 17 (30%) of the 57. The middle ear pressure abnormalities were intermittent and shifted from one ear to the other ear from day to day. Reverse transcriptase polymerase chain reaction was positive for a respiratory virus in 56 (65%) of the 86 illnesses. Rhinovirus was found in 48% and respiratory syncytial virus in 14%. Pathogenic bacteria (Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis) were detected in nasopharyngeal secretion in 29 (34%) of the 86 colds; the bacteria were in high titer (> or =10(3) cfu/mL) in 26 of the 29 positive specimens. None developed illness that required a visit to a physician. Age, detection of a respiratory virus, and presence of bacterial pathogen in the nasopharyngeal secretion had a negligible effect on the occurrence of abnormal tympanometry. Occurrence of negative middle ear pressure in winter-spring colds was significantly greater than in fall colds for unexplained reasons., Conclusions: Transient negative middle ear pressure occurred in two thirds of uncomplicated colds in healthy children. This negative pressure, which may facilitate secondary viral or bacterial otitis media, seems to result from viral infection of the nasopharynx and distal tube causing bilateral eustachian tube dysfunction. Tympanometry provides an objective measure of the potential beneficial effects of investigational treatments on the risk of eustachian tube dysfunction/otitis media.

The common cold is the most prevalent disease in humans. It is generally caused by rhinovirus. Bacterial involvement is rare, and an uncomplicated common cold does not require treatment with antibiotics. The symptoms are not caused by tissue destruction, but rather by the response of the immune system, including the release of kinins and interleukins. The intensity of transmission depends upon the amount of nasal discharge. It is mediated in part by the hands (sometimes via contaminated objects) and partly by aerosols. Rhinovirus is involved in 40% of asthma attacks in school children, and in about 60% of exacerbations in adults with chronic obstructive pulmonary disease. Smoking, stress, and a few types of social contact are all risk factors, whereas alcohol consumption seems to be protective. Exposure to a cold environment is probably of no significance in the pathogenesis. No effective cure is known. The medications in use are all directed exclusively against the symptoms, and especially for pre-school children, they are of doubtful value and potentially harmful.

Objective: To reduce the injudicious use of antibiotics, we developed an educational strategy that focused on parents of pediatric patients and their physicians., Methods: This intervention was conducted in 5 pediatric practices in Arkansas during a 9-month period. Baseline data on parent attitudes about antibiotics and physician practice habits were measured by questionnaire. During the following 36 weeks, an educational videotape about the judicious use of antibiotics was played in waiting rooms. The videotape on antibiotics used a standard script based on the recommendations of the American Academy of Pediatrics. The physicians and staff at each site were actors in the videotape. During week 2 and week 36 of videotape use, parent attitudes were measured again. After the baseline week, the physicians and staff in each site were provided a standard in-service review of the American Academy of Pediatrics recommendations for judicious use of antibiotics. A study nurse recruited patients, administered questionnaires, and reviewed charts on-site., Results: Parents who were exposed to the videotape were significantly less inclined to seek antibiotics for viral infections. Passively provided pamphlets were not read. No significant change in antibiotic prescribing by physicians was seen., Conclusion: Parent-focused passive education tools are effective at changing parent attitudes toward the use of antibiotics. Although physicians have blamed parent attitudes and demands for the overuse of antibiotics, changes in parent attitudes in this study were not associated with changes in prescribing rates. Changes in parent attitudes may be necessary but do not seem sufficient for changes in antimicrobial prescribing patterns.

The aim of the present study was to assess the hypothesis that, when present in nasopharyngeal secretions, Streptococcus pneumoniae. Haemophilus influenzae, and Moraxella catarrhalis play a pathogenic role early in the course of an upper respiratory tract infection. Adults with a clinical diagnosis of acute sinusitis or common cold were enrolled. Participants were randomly assigned in a double-blind manner to receive azithromycin 500 mg daily or placebo for 3 days. The effect of treatment on symptom evolution in the predefined subset of patients with Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis in their nasopharyngeal secretions was assessed. Of 265 patients enrolled, 132 received placebo and 133 azithromycin. Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis was identified in nasopharyngeal secretions of 77 patients (29%). In this predefined subgroup of patients with Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis, resolution of symptoms by day 7 occurred in 73% of those treated with azithromycin compared with 47% of those who received placebo (P=0.007). The median time before resolution of symptoms was 5 days in the azithromycin group compared to 7 days in the placebo group. Respiratory complications requiring antibiotic treatment occurred in 19% of patients in the placebo group and in 3% of the azithromycin group (P=0.025). In the remaining 188 patients without Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis, resolution of symptoms by day 7 was similar in both groups (69% in the placebo group vs. 64% in the azithromycin group [P=0.75]). Antibiotic treatment is of clinical benefit for patients with acute sinusitis or common cold when Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis is present in nasopharyngeal secretions. This observation provides new insights into the pathogenic role of these bacteria in the early stage of the common cold.

Background: We evaluated whether the symptoms and signs and radiologic findings during a common cold are similar in patients who have and have not suffered from recurrent sinusitis., Methods: We recruited 2 series of volunteer cases from February 1, 1996, to December 31, 1996. Twenty-three adults who claimed to have suffered from recurrent sinusitis and 25 who had never had sinusitis were examined during the period of a self-diagnosed cold of 48 to 96 hours' duration and again after 21 days. Symptom scores were recorded, nasoendoscopy and computed tomography scans were performed, and viral and bacterial specimens were taken., Results: The patients with a history of sinusitis had significantly higher symptom scores than the control patients (P=.04) and had radiologic sinusitislike changes more often (65% [15] vs 36% [9]; difference 29% [95% confidence interval, 2%-56%]; P=.04). The viral etiology of the common cold (verified in 67% of the episodes) was similar in both groups. Pathogenic bacteria were isolated from the middle meatus in 24% (6) of the control patients and only 9% (2) of the sinusitis-prone patients (P=.15). On the basis of the symptomatology, radiologic findings, and bacterial cultures only 2 patients in the sinusitis-prone group should have been treated with antimicrobials., Conclusions: Some patients are susceptible to both sinusitislike symptoms and radiologic findings during viral common colds. This may cause them to consult their physicians earlier and more often during viral colds, which may result in unnecessary antibiotic treatments. Nasopharyngeal bacteriological cultures may prove to be useful in ruling out bacterial sinusitis.

Background: Rhinovirus infections in airway epithelial cells in vitro have been shown to upregulate intercellular adhesion molecule-1 (ICAM-1) expression. Epithelial ICAM-1, in its dual role as the major rhinovirus receptor and as adhesion molecule for inflammatory cells may be involved in the pathogenesis of rhinovirus-induced exacerbations of asthma., Objective: We aimed to investigate the effect of experimental rhinovirus 16 (RV16) infection on ICAM-1 expression in bronchial mucosal biopsies in asthma. In addition, the effect of 2 weeks pretreatment with inhaled budesonide (800 microg b.d.) on RV16-associated changes in ICAM-1 expression was studied., Methods: The study had a parallel, placebo-controlled design in 25 steroid-naive nonsmoking atopic asthmatic subjects. After 2 weeks budesonide (BUD) or placebo (PLAC) pretreatment bronchoscopy was performed 2 days before (day -2) and 6 days after (day 6) RV16 inoculation (on days 0 and 1). Immunohistochemical staining for ICAM-1 was performed on snap-frozen bronchial biopsies. ICAM-1 staining intensity on the basal epithelial cells was scored semiquantitatively from 1 (weak) to 3 (intense). Similarly, epithelial intactness was noted (1 = basal cells only, 2 = basal and parabasal cells, 3 = intact epithelium)., Results: ICAM-1 scores were not significantly different between the groups at day -2 (P > or = 0.08). Subsequent RV16 infection was associated with a trend towards an increase in ICAM-1 expression in the BUD-group (P = 0.07), whereas the increase was significant in the PLAC-group (P = 0.03). However, the increase was not significantly different between the groups (P = 0.74). Epithelial intactness score was not different between the groups before RV16 infection (P > or = 0.07), and no significant changes were observed in either group (P > or = 0.59). Moreover, ICAM-1 score did not correlate significantly with epithelium score in either group, at any time-point (P > or = 0.27)., Conclusion: We conclude that an RV16 common cold in atopic asthmatic subjects is associated with increased ICAM-1 expression in the bronchial epithelium, which is not related to epithelial intactness. Glucocorticoid treatment does not appear to prevent the RV16-associated increased ICAM-1 expression. This suggests that other treatment modalities are required to protect against the spreading of infection during rhinovirus-induced exacerbations in asthma.

The antimicrobial susceptibility of 1078 isolates of Haemophilus influenzae, 348 Streptococcus pneumoniae and 258 Moraxella catarrhalis was determined. Overall 15.1% of H. influenzae produced beta-lactamase; 98.8% were susceptible to co-amoxiclav, 85.8% to cefaclor, 96% to clarithromycin and 100% to ciprofloxacin. The majority (94.2%) of M. catarrhalis produced beta-lactamase. The overall prevalence of low-level penicillin resistance (MIC = 0.12-1 mg/L) amongst isolates of S. pneumoniae was 3.4% and that of high-level resistance (MIC > or = 2 mg/L) was 3.7%. Most (96.3%) of the isolates of S. pneumoniae were susceptible to amoxycillin (MIC < or = 0.5 mg/L), 96% to cefaclor (MIC < or = 8 mg/L), 90.7% to clarithromycin (MIC < or = 0.25 mg/L) and 89% to ciprofloxacin (MIC < or = 1 mg/L).

Background: Cold virus infections are associated with asthma attacks and with increased bronchial responsiveness even in normal subjects. Possible mechanisms include epithelial damage, interaction with adhesion molecules or with T-helper cell subsets., Objective: To determine whether colds increase lower airway inflammation, comparing atopic with non-atopic normal subjects., Methods: Thirty healthy volunteers (15 atopic) took part. Baseline tests included viral serology, microbiological culture and polymerase chain reaction for rhinovirus infection (HRV-PCR), histamine bronchial provocation and bronchoscopy. Twenty subjects (eight atopic) underwent repeat tests when they developed a cold., Results: Forced expiratory volume in one second (FEV1) was significantly lower during colds (-0.19 L [95% confidence interval -0.10, -0.29], P = 0.0004) and there was a significant increase in bronchial responsiveness (+0.62 doublings of the dose-response slope [+0.24, +1.00], P = 0.003). Eight subjects (two atopic) had a diagnosed viral infection: two HRV, three coronavirus (HCV), one HRV + HCV, one parainfluenza III (PI) and one respiratory syncytial virus (RSV) (also Haemophilus influenzae). In biopsies, during colds, total eosinophils (EGI+) increased significantly (geometric mean 6.73-fold [1.12,40.46], P = 0.04). Activated eosinophils (EG2+) only increased significantly in the subgroup without diagnosed viral infection and particularly in atopic rhinitics. T-suppressor (CD8+) cells also increased significantly (median + 178.3 cells mm2, P = 0.004). Epithelial expression of intercellular adhesion molecule-1 (ICAM-1) expression increased in four atopic rhinitics during colds. Bronchial washings showed a significant increase in neutrophils (GM 1.53-fold [1.04,2.25], P = 0.02)., Conclusion: Lower airway inflammation was present in atopic and non-atopic normal subjects with colds. Atopic subjects differed in that they were less likely to have positive virological tests and were more likely to show activated eosinophilia in the lower airway, despite a similar spectrum of symptoms.

Background: Upper-respiratory-tract infection is one of the main causes of overuse of antibiotics. We have found previously that bacteria such as Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae can be isolated from the nasopharyngeal secretions of a substantial proportion of adults with upper-respiratory-tract infections. We have assessed the efficacy of co-amoxiclav in patients with common colds but no clinical signs of sinusitis or other indications for antibiotics., Methods: Between January, 1992 and March, 1994, 314 patients who presented to our outpatient clinic with common colds were enrolled in the double-blind, placebo-controlled study. They were randomly assigned 5 days' treatment with co-amoxiclav (375 mg three times daily) or identical placebo. Clinical examinations were done at enrolment and on day 5-7 to assess outcome (cured, persistent symptoms, worse symptoms). Seven patients were excluded after randomisation, seven did not have nasopharyngeal aspiration, and 12 did not return for followup assessment., Findings: Of 300 patients with nasopharyngeal aspirates, 72 had negative bacterial cultures, 167 had cultures positive only for bacteria unrelated to respiratory infections, and 61 had cultures positive for H influenzae, M catarrhalis, or S pneumoniae. At 5-day follow-up of these culture-positive patients, the distribution of outcome was significantly better among co-amoxiclav-treated (n=30) than placebo-treated (n=28) patients (cured 27 vs 4%; persistent symptoms 70 vs 60%; worse symptoms 3 vs 36%; p=0.001). Patients on co-amoxiclav also scored their symptoms significantly lower than patients on placebo (p=0.008). Among culture-negative patients (n=230), the outcome distribution did not differ between the treatment groups (p=0.392)., Interpretation: The majority of patients with upper-respiratory-tract infection do not benefit from antibiotics and side-effects are frequent. However, for the subgroup whose nasopharyngeal secretions contain H influenzae, M catarrhalis, or S pneumoniae, antibiotics are clinically beneficial.

The potential involvement of interleukin-1 (IL-1) in the pathogenesis of experimental rhinovirus colds was examined. Nasal lavages were recovered before and for 5 days after rhinovirus infection from 44 subjects, 22 of whom were randomized to receive prophylaxis with glucocorticoids, while the rest received placebo. Immunoreactive IL-1 beta was significantly increased in subjects who were infected and symptomatic compared with noninfected volunteers or subjects who were infected but asymptomatic. Concentrations of immunoreactive IL-1 beta correlated with levels of kinins and albumin in lavage fluids. Studies of IL-1 bioactivity established that most activity in lavages from infected subjects was IL-1 beta. Glucocorticoid prophylaxis did not inhibit IL-1 production, nor did it significantly affect the symptomatic response to infection or, in a subset of patients, neutrophil infiltration. These data are consistent with the hypothesis that IL-1 could contribute to the pathogenesis of rhinovirus infections.

Evidence suggests that atopic individuals may be predisposed to more severe rhinoviral colds coupled to a worsening of existing airway disease than those with asthma. The role of atopy and IgE levels, as well as their relationship to clinical disease expression have not been defined. We hypothesized that an allergic diathesis modulates rhinoviral colds and have initiated studies of normal, atopic and asthmatic subjects employing experimental rhinoviral infection, with measurements of symptom scores, viral shedding and cultures, albumin in nasal washes and serological responses. Twenty-two subjects (11 normal, 5 atopic, 6 atopic and asthmatic) participated and were inoculated with human rhinovirus serotype 16 (HRV 16). Measurements of neutralizing antibody and viral culture were performed at screening, pre-inoculation, during the cold and at 8-10 weeks convalescence. Daily symptoms were noted, nasal washes done, IgE measured and atopy was diagnosed by skin tests. Seventeen volunteers developed clinical colds as assessed by symptom scores, virus shedding was demonstrated (with positive culture) in all subjects and a fourfold or higher seroconversion occurred in 11/22. Neutralizing HRV antibody developed unexpectedly in 10 subjects between screening and inoculation and the presence of absence of this pre-inoculation antibody determined subsequent severity of colds in normal but not in atopic subjects. Atopic antibody positive individuals developed severe clinical colds that were independent of preinoculation antibody in contrast to normal subjects who developed mild colds in the presence of a neutralizing antibody (P = 0.01). Both atopic and normal antibody negative subjects developed severe colds.(ABSTRACT TRUNCATED AT 250 WORDS)

Objective: Nasal inhalation of steam has been proposed as treatment of viral colds on the assumption that increased intranasal temperature will inhibit replication of rhinovirus (RV). The effect of steam inhalation on RV shedding by infected volunteers was examined in this study., Design: Randomized controlled trial. Volunteers experimentally infected with RV were treated with machine-generated humidified air, which was either hot (active) or at room temperature (placebo). Viral shedding was assessed over the 4 days following treatment., Setting: Local hotel., Participants: Twenty volunteers from the university community who were susceptible to the challenge virus., Intervention: Two 30-minute intranasal treatments, the first at 24 hours after inoculation and the second at 48 hours. The temperature of active vapor was 42 degrees C to 44 degrees C and of placebo vapor was 22 degrees C., Main Outcome Measures: Viral titers in nasal washings on each of 5 days following inoculation., Results: Mean viral titers prior to the first treatment were 10(1.7) tissue culture infectious doses per milliliter in the active group and 10(1.5) in the placebo group. Mean titers for the next 4 days were 10(1.7), and 10(1.7), 10(1.2), and 10(0.9)/mL in the active group and 10(1.8), 10(1.9), 10(1.6), and 10(0.7)/mL in the placebo group (no significant difference). The proportion of volunteers who shed virus on each day was also similar in the two groups., Conclusion: Two nasal inhalation treatments with steam had no effect on viral shedding in volunteers with experimental RV colds.

Delineation of the pathogenesis of symptoms during common colds is the overall aim of this work. The studies included in this thesis have focused on the histopathologic changes in the nasal mucosa produced by infection with respiratory viruses. The accepted concept when these studies were undertaken was that cold symptoms were caused by destruction of nasal epithelium by virus and that epithelial damage sometimes led to secondary bacterial infection evidenced by purulent nasal secretions. The pathogenesis of cold symptoms has been reviewed in this thesis based on investigations by others and my own research. Chapter 1 described the clinical design of a naturally acquired cold model and an experimental rhinovirus cold model which were used. The advantages of the experimental model over the natural cold model are that the viral etiology is known and that volunteers can be studied beginning at viral inoculation rather than onset of symptoms. Unfortunately, the experimental model is very expensive. Chapter 2 reviewed the histopathology of the nasal mucosa during colds. The degree of destruction of the mucosa during naturally acquired colds reported in the literature has varied. We did not detect any discernible damage of the epithelium by light and scanning electron microscopy in naturally acquired colds. We repeated the study in volunteers with rhinovirus colds and again did not find any damage to the surface epithelium (light microscopy). Although different viruses may cause epithelial damage in naturally acquired colds, in rhinovirus colds the epithelium of the anterior part of the inferior turbinate is not destroyed. There was an early influx of neutrophils into the nasal mucosa in patients both with naturally acquired colds (day 2 after onset) and with experimental rhinovirus colds. This discovery in combination with the minimal damage of the nasal epithelium led to formulation of a new hypothesis of how cold symptoms may be produced. The influx of neutrophils might be a direct response to viral infection and/or may reflect the release of a cascade of inflammatory mediators which are responsible in part for the symptoms. Naclerio et al (1988) has since shown that the number of neutrophils in nasal secretions increases early in rhinovirus colds. This increase correlated nicely with the symptoms. In addition, Turner (1988) demonstrated the elaboration of a chemoattractant factor for neutrophils by cell cultures infected with rhinovirus type 39. Chapter 3 focused on the location of rhinovirus replication in the nose and nasopharynx. The entire mucosal lining of the nasal cavities was not infected during the first week of a rhinovirus colds.(ABSTRACT TRUNCATED AT 400 WORDS)

Ohio HeLa cells in multichamber slides were inoculated with nasal samples from patients presenting with common cold symptoms and incubated at 33 degrees C with gentle shaking for 48 hours. The cultures were fixed with cold acetone, and viral antigens were detected by immunofluorescence using an antirhinovirus type 2 (HRV-2) polyclonal serum. Of 158 samples, 58 (36.7%) and 57 (36%) were positive for HRV by virus isolation (confirmed by acid lability test) and by culture-amplified immunofluorescent (CAIF) test, respectively. The correlation between the two tests was highly significant (P = 0.0001). Nasal washings or nasal/throat swabs were equally suitable for detecting virus by isolation but not by CAIF. On the other hand, nasal washings were better than nasal/throat swabs for detecting HRV by CAIF. In an ELISA system, the polyclonal anti-HRV-2 serum recognized a rhinovirus antigen expressed in situ within 48 hr postinfection by all the 11 HRV serotypes investigated. However, 60 hr postinfection, the anti-HRV-2 serum recognized only homologous and closely related HRV antigens. These results suggest that a rhinovirus "common" antigen may be expressed some 48 hr after infection of Ohio HeLa cells with rhinoviruses. The CAIF test provides a sensitive, rapid and reliable procedure to detect wild-type rhinovirus infection as well as a clear alternative to detection by isolation.

Background: The inflammatory response of the airway microcirculation in rhinitis and asthma may be recorded as luminal entry of plasma macromolecules (mucosal exudation). This study examines the exudative responsiveness of the subepithelial microvessels in subjects with and without common cold after inoculation with coronavirus., Methods: The airway mucosa was exposed to exudative concentrations of histamine (40 and 400 micrograms/ml) before and six days after inoculation. To assess whether mucosal penetration of a topically applied agent was altered, nasal absorption of chromium-51 labelled ethylene diamine tetraacetic acid (51Cr-EDTA, MW 372) was also examined. A nasal pool technique kept the challenge and tracer solutes in contact with the same ipsilateral mucosal surface. Concentrations of albumin in lavage fluids were measured as an index of mucosal exudation of plasma. Nasal absorption of 51Cr-EDTA was determined by the cumulated 24 hour urinary excretion of radioactivity., Results: Nine subjects developed common cold after coronavirus inoculation and 10 remained healthy. Histamine produced concentration dependent mucosal exudation of plasma in all subjects before and after coronavirus inoculation. In subjects with common cold, however, the histamine-induced mucosal exudation was significantly augmented compared with the group without common cold. This exudative hyperresponsiveness is not explained by an increased baseline exudation because the lavage regimen used produced comparably low baseline exudation in both groups of subjects, nor is it explained by an increased penetration of topical histamine because the ability of the nasal mucosa to absorb 51Cr-EDTA was not significantly increased in the subjects with common cold., Conclusions: An increased proclivity of the airway subepithelial microcirculation to respond with plasma exudation develops during coronavirus-induced common cold. This specific exudative hyperresponsiveness may be a feature of inflammatory airway diseases.

Objective: To study the role of respiratory viruses in exacerbations of asthma in adults., Design: Longitudinal study of 138 adults with asthma., Setting: Leicestershire Health Authority., Subjects: 48 men and 90 women 19-46 years of age with a mean duration of wheeze of 19.6 years. 75% received regular treatment with bronchodilators; 89% gave a history of eczema, hay fever, allergic rhinitis, nasal polyps, or allergies; 38% had been admitted to hospital with asthma., Main Outcome Measures: Symptomatic colds and asthma exacerbations; objective exacerbations of asthma with > or = 50 l/min reduction in mean peak expiratory flow rate when morning and night time readings on days 1-7 after onset of symptoms were compared with rates during an asymptomatic control period; laboratory confirmed respiratory tract infections., Results: Colds were reported in 80% (223/280) of episodes with symptoms of wheeze, chest tightness, or breathlessness, and 89% (223/250) of colds were associated with asthma symptoms. 24% of 115 laboratory confirmed non-bacterial infections were associated with reductions in mean peak expiratory flow rate > or = 50 l/min through days 1-7 and 48% had mean decreases > or = 25 l/min. 44% of episodes with mean decreases in flow rate > or = 50 l/min were associated with laboratory confirmed infections. Infections with rhinoviruses, coronaviruses OC43 and 229E, influenza B, respiratory syncytial virus, parainfluenza virus, and chlamydia were all associated with objective evidence of an exacerbation of asthma., Conclusions: These findings show that asthma symptoms and reductions in peak flow are often associated with colds and respiratory viruses; respiratory virus infections commonly cause or are associated with exacerbations of asthma in adults.

Colds are a common clinical condition, caused by a variety of pathogens. This article reviews the etiology of the cold, proposed cures, symptomatic relief, method of transmission, and advice for patients. Transmission through indirect contact, or self-inoculation, seems more common than was once thought. Experimental antiviral agents hold some promise; in the meantime, symptomatic relief is available.

We studied the mucosal exudation of plasma in relation to pathophysiological events during an induced common cold. Coronavirus 229E was inoculated nasally in 20 healthy volunteers under controlled conditions. Ten volunteers developed the common cold, determined by symptom scores and serology. The bulk plasma exudate was monitored, using fibrinogen (MW 340 kD) in nasal lavage fluids as an endogenous marker. Following inoculation, anterior rhinoscopy and objective registrations of nasal mucosal temperature, nasal discharge weight, and nasal blockage index by peak expiratory air flow, were followed twice daily for 6 days. Mucosal plasma exudation, as assessed by fibrinogen in lavage fluids, increased hundredfold after virus inoculation, concomitantly with the subjective symptoms and objective physiological changes. We propose that this exudation reflects the degree of subepithelial inflammation, and suggests that plasma bulk exudate, including all potent plasma protein systems may be involved in the resolution of acute viral rhinitis--common cold.

This study's objective was to determine if the combination of pseudoephedrine hydrochloride and atropine sulfate attenuates the symptomatic and pathophysiologic response of individuals to experimental rhinovirus infection when given after illness begins. Forty-three susceptible adult volunteers were challenged with rhinovirus type 39 and randomly assigned to 1 of 2 treatment groups. Twenty-one subjects were treated with the active medication (0.3 mg atropine sulfate and 60 mg pseudoephedrine) and 22 subjects were treated with inert capsules identical in appearance. Treatments were administered 4 times daily beginning approximately 24 hours after rhinovirus challenge and extending for 5 days. Before challenge and on each of 5 treatment days, all volunteers were asked to rate symptom severity and were evaluated for secretion production (weighted tissues), nasal patency (active posterior rhinomanometry), nasal clearance (dyed saccharin technique), eustachian tube function (9-step test), and middle ear status (tympanometry). Twenty subjects in each group were infected with rhinovirus type 39 and were included in the efficacy analysis. Between-group comparisons showed no significant differences in total symptom scores, combined nasal symptom score, secretion production, or the frequencies of persons with eustachian tube obstruction or abnormal middle ear pressures. However, an objective measure of nasal congestion was significantly lower in the active treatment group. The nasal mucociliary clearance rate was significantly more impaired in that group. Side effects consistent with anticholinergic activity were reported more frequently in the active treatment group.

Six (18%) of 34 healthy, asymptomatic young adults had mucosal thickening or fluid in the paranasal sinuses on screening magnetic resonance imaging (MRI) examination. When 19 of these subjects were challenged with rhinovirus, 18 became infected. Twelve of the 18 infected subjects had technically satisfactory serial MRI examinations, and four (33%) of these developed MRI abnormalities of the ethmoid or antral sinuses that were temporally associated with the acute infection. The mean total nasal secretion weights were 22 gm/5 days in the four subjects whose MRI abnormalities were associated with the acute infection compared with 5.5 gm/5 days in the eight subjects who had normal MRI examinations during the acute infection (p = 0.06). Abnormalities of the paranasal sinuses, which were associated with increased volumes of nasal secretion, were detected by MRI examination during rhinovirus infection. These abnormalities may have a role in the pathogenesis of acute sinusitis associated with colds.

Objective: To determine whether naproxen, a propionic acid inhibitor of cyclooxygenase, alters the course of experimental rhinovirus colds., Design: A randomized, double-blind, controlled trial., Setting: Rhinovirus challenge model in volunteers cloistered in individual hotel rooms., Volunteers: Eighty-seven healthy young adults with serum neutralizing antibody titers of less than or equal to 1:2 to the challenge virus; 79 were evaluable., Intervention: Thirty-nine participants received naproxen (loading dose, 400 mg or 500 mg followed by 200 mg or 500 mg three times daily for 5 days). Forty participants received placebo. Treatment was started 6 hours after viral challenge., Measurements: Daily measurement of viral titers, symptoms, nasal mucus production, and nasal tissue use; incidence of infection and illness; and measurement of homotypic serum neutralizing antibody responses., Results: Viral titers and serum homotypic antibody responses were similar in the naproxen and placebo groups. Significant reductions in headache, malaise, myalgia, and cough occurred in the naproxen group. A 29% reduction was noted in the total (5-day) symptom score in the naproxen group (95% CI, 16% to 42%)., Conclusion: Naproxen treatment did not alter virus shedding or serum neutralizing antibody responses in participants with experimental rhinovirus colds, but it had a beneficial effect on the symptoms of headache, malaise, myalgia, and cough. Prostaglandins may be among the inflammatory mediators that play a role in the pathogenesis of rhinovirus colds.

I have been asked to stand back and describe in broad terms the view I have had of common colds--probably the most frequent of acute human diseases and a long-lasting scientific problem--and in particular our recent work on antivirals. I should be able to do this for two reasons. Like everyone else I have suffered from colds, but in addition I have been studying the problem from the virological and clinical point of view for over 35 years--for the last 31 at the Common Cold Unit, Salisbury. As a result I may have problems with perspective--it is not possible to give a personal view and at the same time to describe something from every possible angle, and quite impossible to be comprehensive, but I have done my best and readers will make their own judgements and corrections.

Rhinoviruses are the main etiologic agents of infectious common colds, which represent about 40% of the acute respiratory infections in man. The antigenic diversity of rhinoviruses precludes any prevention by vaccination. Within the last 20 years, efforts have therefore concentrated on chemoprophylaxis or chemotherapy with antiviral agents. Interferons (alpha and beta) administered intranasally at high doses, exerted a significant prophylactic activity in volunteers inoculated with rhinoviruses or in the course of epidemics in families. By contrast, the therapeutic activity of interferons is almost nonexistent, which greatly limits their practical interest. Various synthetic chemicals exert a marked and selective inhibitory effect on the replication of various serotypes of rhinoviruses in cell cultures. In the absence of an animal model of rhinovirus infection, in vivo studies of these molecules have been performed in human volunteers, chiefly at the Common Cold Research Unit in Salisbury (Great Britain). 3 synthetic compounds (an imidazothiazole, a benzimidazole derivative and a piperazinyl-pyridazine) have exerted a significant prophylactic activity, especially marked with the latter. None of these compounds, however, was active when administered after the infectious challenge. The search for selective anti-rhinovirus compounds is still going on; it will probably be facilitated through a combination of structural studies of rhinovirus capsids (or of their cellular receptors) with computer-assisted design of synthetic molecules. The recent observation of the influence of psychological factors on the propensity of rhinovirus-infected subjects to develop clinically apparent common cold must be taken into account in future studies.

Results from two studies involving challenge with respiratory syncytial viruses showed that volunteers who developed colds were more sensitive to a visually distracting pattern presented prior to virus challenge than were volunteers who did not get a cold. Volunteers with sub-clinical infections reported more illusions after virus challenge than they had done before, whereas uninfected volunteers and those with colds tended to report fewer illusions on the second test. These effects did not occur when volunteers were challenged with either a coronavirus or rhinovirus. Overall, the results confirm that behavioural measures may be related to susceptibility to subsequent illness, and that viral infections may influence visual perception. They also show that the effects vary according to the nature of the infecting agent, which agrees with results from studies looking at other aspects of behaviour.