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Rhinovirus produces nonspecific activation of lymphocytes through a monocyte-dependent mechanism.

There is evidence that rhinovirus (RV) infections are frequent causes of increased asthmatic symptoms and can specifically enhance allergic inflammation in the airway. To further define effects of RV infection on cellular immunity, we have begun to develop in vitro models for study. When human PBMC were incubated with 35S-labeled RV16, specific binding via ICAM-1 on monocytes was observed. Incubation of PBMC with RV also led to a dose-related increase in the expression of the early activation marker CD69 on 30 to 70% of T cells. The RV16-induced increases in CD69 were blocked by anti-ICAM-1 mAb, and were not elicited by UV-inactivated (noninfectious) virus. The degree of CD69 enhancement correlated with the number of monocytes in mixtures of PBMC, did not occur in monocyte-depleted cultures, and was mediated by one or more soluble factor(s). RV also induced secretion of IFN-gamma from both peripheral blood T cells and NK cells, and IFN-gamma mRNA was greatest in T cells that were CD69+. Finally, supernatant from RV-activated CD3+CD69+ cells had biologic activity that promoted eosinophil survival in vitro; this RV16-associated activity was blocked when co-incubations were performed with IFN-gamma mAbs. These observations suggest that RV nonspecifically activates a large proportion of T cells through a monocyte-dependent mechanism. Such changes in vivo could enhance airway inflammation, and this may include effects on inflammatory cells in the airways of allergic individuals.

Adult↗

The effectiveness of vitamin C in preventing and relieving the symptoms of virus-induced respiratory infections.

BACKGROUND: An ever increasing demand to evaluate the effect of dietary supplements on specific health conditions by use of a "significant scientific" standard has prompted the publication of this study. OBJECTIVE: To study the effect of megadose Vitamin C in preventing and relieving cold and flu symptoms in a test group compared with a control group. DESIGN: Prospective, controlled study of students in a technical training facility. SUBJECTS: A total of 463 students ranging in age from 18 to 32 years made up the control group. A total of 252 students ranging in age from 18 to 30 years made up the experimental or test group. METHOD: Investigators tracked the number of reports of cold and flu symptoms among the 1991 test population of the facility compared with the reports of like symptoms among the 1990 control population. Those in the control population reporting symptoms were treated with pain relievers and decongestants, whereas those in the test population reporting symptoms were treated with hourly doses of 1000 mg of Vitamin C for the first 6 hours and then 3 times daily thereafter. Those not reporting symptoms in the test group were also administered 1000-mg doses 3 times daily. RESULTS: Overall, reported flu and cold symptoms in the test group decreased 85% compared with the control group after the administration of megadose Vitamin C. CONCLUSION: Vitamin C in megadoses administered before or after the appearance of cold and flu symptoms relieved and prevented the symptoms in the test population compared with the control group.

Adolescent↗

Rhinovirus illnesses during infancy predict subsequent childhood wheezing.

BACKGROUND: The contribution of viral respiratory infections during infancy to the development of subsequent wheezing and/or allergic diseases in early childhood is not established. OBJECTIVE: To evaluate these relationships prospectively from birth to 3 years of age in 285 children genetically at high risk for developing allergic respiratory diseases. METHODS: By using nasal lavage, the relationship of timing, severity, and etiology of viral respiratory infections during infancy to wheezing in the 3rd year of life was evaluated. In addition, genetic and environmental factors that could modify risk of infections and wheezing prevalence were analyzed. RESULTS: Risk factors for 3rd year wheezing were passive smoke exposure (odds ratio [OR]=2.1), older siblings (OR=2.5), allergic sensitization to foods at age 1 year (OR=2.0), any moderate to severe respiratory illness without wheezing during infancy (OR=3.6), and at least 1 wheezing illness with respiratory syncytial virus (RSV; OR=3.0), rhinovirus (OR=10) and/or non-rhinovirus/RSV pathogens (OR=3.9) during infancy. When viral etiology was considered, 1st-year wheezing illnesses caused by rhinovirus infection were the strongest predictor of subsequent 3rd year wheezing (OR=6.6; P < .0001). Moreover, 63% of infants who wheezed during rhinovirus seasons continued to wheeze in the 3rd year of life, compared with only 20% of all other infants (OR=6.6; P < .0001). CONCLUSION: In this population of children at increased risk of developing allergies and asthma, the most significant risk factor for the development of preschool childhood wheezing is the occurrence of symptomatic rhinovirus illnesses during infancy that are clinically and prognostically informative based on their seasonal nature.

Child, Preschool↗

Acute bacterial sinusitis in adults: management in the primary care setting.

Sinus disease is inherently associated with viral upper respiratory tract infections and occurs in 90% of individuals with the common cold. Acute bacterial sinusitis occurs in 0.5 to 2% of these individuals. Although the diagnosis of acute bacterial sinusitis is usually based on physical findings, no one sign or symptom is either sensitive or specific for sinusitis. The predictive power can be significantly improved when all signs and symptoms are combined into a clinical impression. Imaging studies have not been shown to be cost effective in the initial assessment and treatment of patients in the primary care setting. Simple plain films may be indicated to resolve the diagnosis in patients with an equivocal history or to follow patients admitted to hospital with severe sinus disease. The initial management of acute sinusitis should be directed toward the relief of symptoms with a 7-day course of decongestants and mucoevacuents. For patients who fail to improve with symptomatic treatment, a 10-day course of amoxicillin is recommended. Second line antibiotics should be initiated if improvement is not seen within 72 to 96 hours.

Adult↗

Transient autoantibodies with elevated complement levels in common viral diseases.

Autoantibodies including rheumatoid factor (RF), anti-DNA antibody (ADA), and anti-nuclear factor (ANF) in addition to cold agglutinin and heterophil antibody titers were tested for in a total of 219 patients with common viral diseases. The diseases included varicella, influenza, measles, mumps, herpes zoster, hand-foot-mouth syndrome, and exanthem subitum . A high incidence of RF (23%) was demonstrated in varicella patients, and ADA and ANF (16% and 12%, respectively) were most frequently detected in the influenza cases. Those autoantibodies were most frequently found in patients with influenza. Each serum complement component and total hemolytic complement (CH50) were also assayed. Elevated levels of the fourth (C4) and ninth (C9) components of complement, along with elevated CH50, were observed in most patients. Follow-up studies indicated that those autoantibodies as well as other antibodies disappeared 3 to 8 weeks after the onset of infection. The present study indicates that substantial but transient alterations in the immune system accompanied by autoimmune phenomena and elevated levels in the complement components can occur in viral infections.

Adolescent↗

Nasal mucosa in natural colds: effects of allergic rhinitis and susceptibility to recurrent sinusitis.

The mechanisms of virus-induced airway hyperresponsiveness in asthma and allergy and the failure of host defence in patients suffering from secondary airway infections are still largely unknown. The aim of this study was to examine whether the presence of allergic rhinitis or susceptibility to recurrent sinusitis affects the structural and cellular changes in nasal mucosa during natural colds and convalescence. We compared the mucosal changes in biopsy samples during acute natural colds (days 2-4 of illness) and convalescence (3 weeks later) in patients with allergic rhinitis (n = 9), patients with susceptibility to sinusitis (n = 19) and healthy controls (n = 20). We saw similarly increased numbers of mucosal T and B lymphocytes and mast cells and increased vascular density during the acute colds compared to convalescence in all the three groups. The allergic subjects had elevated levels of eosinophils in the acute phase (P = 0.03), and the allergic and sinusitis-prone subjects had elevated levels of epithelial T cells (P = 0.04) and low levels of mast cells (P = 0.005) in convalescence compared to the control group. The sinusitis-prone subjects lacked intraepithelial cytotoxic cells in convalescence. In the allergic subjects, the reticular basement membrane was thicker in the acute phase compared to the convalescence (P = 0.05). These results suggest that various cells of the airways, including inflammatory and structural cells, are involved during viral respiratory infections in subjects with allergic rhinitis. The small numbers of mast cells and cytotoxic lymphocytes in the sinusitis-prone subjects may be related to their susceptibility to bacterial complications.

Acute Disease↗

Pathobiology of neuropathic pain.

This review deals with physiological and biological mechanisms of neuropathic pain, that is, pain induced by injury or disease of the nervous system. Animal models of neuropathic pain mostly use injury to a peripheral nerve, therefore, our focus is on results from nerve injury models. To make sure that the nerve injury models are related to pain, the behavior was assessed of animals following nerve injury, i.e. partial/total nerve transection/ligation or chronic nerve constriction. The following behaviors observed in such animals are considered to indicate pain: (a) autotomy, i.e. self-attack, assessed by counting the number of wounds implied, (b) hyperalgesia, i.e. strong withdrawal responses to a moderate heat stimulus, (c) allodynia, i.e. withdrawal in response to non-noxious tactile or cold stimuli. These behavioral parameters have been exploited to study the pharmacology and modulation of neuropathic pain. Nerve fibers develop abnormal ectopic excitability at or near the site of nerve injury. The mechanisms include unusual distributions of Na(+) channels, as well as abnormal responses to endogenous pain producing substances and cytokines such as tumor necrosis factor alpha (TNF-alpha). Persistent abnormal excitability of sensory nerve endings in a neuroma is considered a mechanism of stump pain after amputation. Any local nerve injury tends to spread to distant parts of the peripheral and central nervous system. This includes erratic mechano-sensitivity along the injured nerve including the cell bodies in the dorsal root ganglion (DRG) as well as ongoing activity in the dorsal horn. The spread of pathophysiology includes upregulation of nitric oxide synthase (NOS) in axotomized neurons, deafferentation hypersensitivity of spinal neurons following afferent cell death, long-term potentiation (LTP) of spinal synaptic transmission and attenuation of central pain inhibitory mechanisms. In particular, the efficacy of opioids at the spinal level is much decreased following nerve injury. Repeated or prolonged noxious stimulation and the persistent abnormal input following nerve injury activate a number of intracellular second messenger systems, implying phosphorylation by protein kinases, particularly protein kinase C (PKC). Intracellular signal cascades result in immediate early gene (IEG) induction which is considered as the overture of a widespread change in protein synthesis, a general basis for nervous system plasticity. Although these processes of increasing nervous system excitability may be considered as a strategy to compensate functional deficits following nerve injury, its by-product is widespread nervous system sensitization resulting in pain and hyperalgesia. An important sequela of nerve injury and other nervous system diseases such as virus attack is apoptosis of neurons in the peripheral and central nervous system. Apoptosis seems to induce neuronal sensitization and loss of inhibitory systems, and these irreversible processes might be in common to nervous system damage by brain trauma or ischemia as well as neuropathic pain. The cellular pathobiology including apoptosis suggests future strategies against neuropathic pain that emphasize preventive aspects.

Animals↗

[Factors of recurrence of intraepithelial lesions of the uterine cervix].

MATERIAL AND METHODS: A retrospective study (1994-1996) of 282 cases of intraepithelial lesions treated in the Gynecology Services of Coimbra University Hospitals and subsequent follow-up (9-45 months). The following parameters were evaluated as recurrence factors: the patient's age, lesion degree, associated HPV infection, treatment type, safety margin in the ablative treatments and interval free of illness. RESULTS: Of the 282 cases, 72.4% (N = 204) corresponded to HSIL and 27.6% (N = 78) to LSIL. The patients' mean was 36.3 +/- 9.1 [19-67] years. The most commonly used treatment types were the LLETZ (large loop excision of the transformation zone) (76.9%) followed by CO2 LASER vaporization (16%) and finally cold-knife conization (7.1%). The safety margins were determined in 184 cases and, on average, were of 3.2 +/- 2.4 [1-10] mm. Forty-four recurrences occurred (15.6%) of which 75% corresponded to HSIL lesions (N = 33) and 25% (N = 11) to LSIL. From the total number of recurrences the association to HPV infection was found in 24 of the cases (54.5%) and 75% of these (N = 19) corresponded to HSIL. The average age in the recurrence group was 38.2 +/- 8.7 [21-53] years and 35.9 +/- 9.2 [19-67] years in the group without recurrences (p > 0.05). In the LSIL group treated with CO2 LASER (N = 32) the recurrence rate was 15.6% versus 13.3% in the group treated with LLETZ (N = 45). In the HSIL that were treated with CO2 LASER vaporization (N = 13) the recurrence rate was 23%; in those treated with LLETZ (N = 172) there were 16.2% recurrences and in the group submitted to cold-knife conization (N = 19) that rate was 10.5%. CONCLUSIONS: The total rate of recurrence was 15.6% with the greatest incidence of lesions associated to HPV (p > 0.05). Regarding the particular case of the HSIL, a great number of recurrences with the destructive treatments (CO2 LASER) was observed when compared to the ablative treatments (cold-knife conization or LLETZ).

Adult↗

Rhinovirus and the lower respiratory tract.

Human rhinoviruses (HRVs) are well-recognised causes of common colds and associated upper respiratory tract complications such as sinusitis and otitis media. This article reviews information linking HRV infection to illness in the lower respiratory tract. HRVs are capable of efficient replication in vitro at temperatures present in the tracheobronchial tree and have been shown to cause productive infection, elaboration of cytokines and chemokines, and up-regulation of cell surface markers in human bronchial epithelial cells. In situ hybridisation studies have proven that HRV infection occurs in the tracheobronchial tree following experimental infection. Clinical studies report that HRV infection is the second most frequently recognised agent associated with pneumonia and bronchiolitis in infants and young children and commonly causes exacerbations of pre-existing airways disease in those with asthma, chronic obstructive pulmonary disease or cystic fibrosis. HRV infection is associated with one-third to one-half of asthma exacerbations depending on age and is linked to asthma hospitalisations in both adults and children. Limited information implicates HRV infection as a cause of severe lower respiratory tract illness in older adults and in highly immunocompromised hosts, particularly bone marrow transplant recipients. More information is needed about the pathogenesis of HRV infection with regard to lower respiratory tract complications in these diverse patient groups. Given the large unmet medical need associated with HRV infections, safe and effective antiviral agents are needed for both prevention and treatment of these infections.

Adolescent↗

Reversible merger of membranes at the early stage of influenza hemagglutinin-mediated fusion.

Fusion mediated by influenza hemagglutinin (HA), a prototype fusion protein, is commonly detected as lipid and content mixing between fusing cells. Decreasing the surface density of fusion-competent HA inhibited these advanced fusion phenotypes and allowed us to identify an early stage of fusion at physiological temperature. Although lipid flow between membranes was restricted, the contacting membrane monolayers were apparently transiently connected, as detected by the transformation of this fusion intermediate into complete fusion after treatments known to destabilize hemifusion diaphragms. These reversible connections disappeared within 10-20 min after application of low pH, indicating that after the energy released by HA refolding dissipated, the final low pH conformation of HA did not support membrane merger. Although the dynamic character and the lack of lipid mixing at 37 degrees C distinguish the newly identified fusion intermediate from the intermediate arrested at 4 degrees C described previously, both intermediates apparently belong to the same family of restricted hemifusion (RH) structures. Because the formation of transient RH structures at physiological temperatures was as fast as fusion pore opening and required less HA, we hypothesize that fusion starts with the formation of multiple RH sites, only a few of which then evolve to become expanding fusion pores.

Cell Line↗

Reducing agents inhibit rhinovirus-induced up-regulation of the rhinovirus receptor intercellular adhesion molecule-1 (ICAM-1) in respiratory epithelial cells.

Rhinoviruses are the major cause of common colds and of asthma exacerbations. Intercellular adhesion molecule-1 (ICAM-1) has a central role in airway inflammation and is the receptor for 90% of rhinoviruses. Rhinovirus infection of airway epithelium induces ICAM-1. Because redox state is directly implicated in inflammatory responses via molecular signaling mechanisms, here we studied the effects of reducing agents on rhinovirus-induced ICAM-1 expression, mRNA up-regulation, promoter activation, and nuclear factor activation. To investigate the effects of rhinovirus infection on the intracellular redox balance, we also studied whether rhinovirus infection triggers the production of reactive oxygen species. We found that reduced (GSH) but not oxidized (GSSG) glutathione (1-100 microM) inhibited in a dose-dependent manner rhinovirus-induced ICAM-1 up-regulation and mRNA induction in primary bronchial and A549 respiratory epithelial cells. GSH but not GSSG also inhibited rhinovirus-induced ICAM-1 promoter activation and rhinovirus-induced NF-kB activation. In parallel, we found that rhinovirus infection induced a rapid increase of intracellular superoxide anion that was maximal at the time of NF-kB activation. This oxidant generation was completely inhibited by GSH. We conclude that redox-mediated intracellular pathways represent an important target for the therapeutic control of rhinovirus-induced diseases.

Animals↗

Differential diagnosis of bovine teat lesions.

Teat lesions affect the dairyman by interfering with the milking process or by increasing the likelihood of intramammary infection. Lesions where the skin is broken are frequently infected. The viral, chemical, environmental, and equipment-induced lesions that lead to ulceration, hemorrhage, and scabbing are all associated with increased intramammary infection; however, this association does not necessarily hold true with the less severe conditions. The dry and flakey skin seen with certain teat dips, lime, or sunburn, the common teat-end callous condition, and the mild, temporary congestion or edema sometimes seen after machine milking usually do not lead to increased intramammary infection. When investigating a problem of increased intramammary infection, other factors should be discussed with the dairyman before suggesting that these conditions are the cause of the problem. Before making a diagnosis of machine-induced lesions, the milking equipment should be carefully inspected and tested. Although the equipment can and frequently does cause lesions, it rarely does so if it is properly set or maintained. Maintenance of inflations, pulsators, vacuum regulators, and vacuum pumps will frequently reveal the source of the problem. In most cases, an equipment malfunction must be quite severe to result in teat injury. Many teat-lesion problems are seasonal in occurrence. The problem will frequently subside in the spring only to reoccur in mid fall. In the midwestern United States, most teat-lesion problems occur from November to April. When investigating a teat-lesion complaint, a large proportion of the herd should be examined.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Rhinovirus stimulation of interleukin-8 in vivo and in vitro: role of NF-kappaB.

Neutrophil infiltration is a well-documented early event in the pathogenesis of rhinovirus (RV) infections. To further understand the mechanisms responsible for this neutrophilia, we determined whether interleukin (IL)-8 was present at sites of experimental RV infection in vivo and characterized the mechanism(s) by which RV stimulates IL-8 production in vitro. IL-8 was readily detectable in the nasal washings of all normal volunteers and did not increase with sham nasal inoculation. In contrast, RV infection caused a significant additional increase in nasal IL-8, the levels of which peaked 48-72 h after virus inoculation. RV was a potent stimulator of IL-8 protein production by A549 epithelial-like cells, MRC-5 fibroblasts, and normal human bronchial epithelial cells in vitro. This induction was associated with a significant increase in IL-8 mRNA accumulation and gene transcription. RV also stimulated IL-8 promoter-driven luciferase activity. This stimulation was significantly decreased by mutation of the nuclear factor (NF)-IL-6 site and was completely abrogated by mutation of the NF-kappaB site in this promoter. In addition, NF-kappaB-DNA binding activity was rapidly induced in RV-infected cells. This inducible binding was made up of p65 and, to a lesser extent, p50 NF-kappaB moieties. These studies demonstrate that IL-8 is present in normal nasal secretions and that the levels of IL-8 are further increased after RV infection. They also demonstrate that RVs are potent stimulators of IL-8 production and that this induction is mediated, at least in part, by an NF-kappaB-dependent transcriptional activation pathway. IL-8 may contribute to the pathogenesis of RV infection, and NF-kappaB activation may be a central event in RV-induced pathologies.

Adult↗

Infection and associated risk factors in the immediate postoperative period of pediatric liver transplantation: a study of 176 transplants.

OBJECTIVE: To describe the characteristics of infections occurring in the immediate postoperative period of orthotopic liver transplantation (OLT) in children in a pediatric intensive care unit (PICU) and the associated risk factors. DESIGN: Retrospective cohort study. SETTING: Multidisciplinary 16-bed pediatric intensive care unit in a tertiary university hospital. PATIENTS: One hundred and thirty-three pediatric patients (range 6M to 22 yr) who underwent 176 liver transplantations and were admitted to the pediatric intensive care unit for at least 48 h. RESULTS: A total of 180 infectious episodes (IE) occurred in 78 (59%) patients who underwent 96 (54.5%) liver transplantations (1.35 IE/patient; 1.02 IE/transplantation). The mean stay was 15.4 +/- 1.1 d (mean +/- SD) and 22 patients died in the pediatric intensive care unit. One hundred and thirty-one IE (72.8%) were bacterial, 31 (17.2%) fungal, and 14 (7.8%) mixed bacterial and fungal. 39% of the IE appeared in the first postoperative week and 27% in the second postoperative week. The most common sites of infection were abdomen (48.3%) and blood stream (26.1%). Bacteria, alone or with fungi, were present in 145 IE (1.1 IE/patient). Gram-positive aerobic bacteria (63%) predominated over gram-negative bacteria (54%) and fungi. Fungi were present in 45 IE; 53.4% of the infections occurred in lung (73% yeasts). The risk factors for infection that were identified were related with younger age, lower body weight, longer cold ischemia time, partial graft, and the volume of packed red blood cell transfusions. Infected patients had more postoperative complications and longer stay in the PICU (21 +/- 16 vs. 8 +/- 6 d), but no increase in mortality. The risk of infection increased 2.38 times with partial grafts and 1.1 times with each intraoperative transfusion of 20 ml/kg of packed red blood cells (RBC). CONCLUSIONS: Infection in the immediate postoperative period of pediatric OLT was related with a high morbidity but was not related significantly with increased mortality. The main risk factors for infection in the postoperative period of OLT were related essentially with small recipient size and the inherent complexity of the operation. Routine oropharyngeal decontamination is recommended, as well as early administration of oral nystatin in preoperative intestinal decontamination. The risk of infection increased 2.38 times with partial grafts and 1.1 times with the transfusion of every 20 ml of packed RBC.

Adolescent↗

Absence of the Kilifi mutation in the rhinovirus-binding domain of ICAM-1 in a Caucasian population.

Human rhinoviruses (HRV), responsible for approximately 60% of the common colds, are divided into two groups, according to their receptor specificity. The major group of HRVs gains access to human cells by binding to the intercellular adhesion molecule-1 (ICAM-1), whereas HRVs of the minor group use members of the low-density lipoprotein receptor (LDLR) family for cell entry. Previous studies confirmed that the HRV-binding region of ICAM-1 is located in the amino-terminal immunoglobulin-like (Ig) domain 1, which is encoded by exon 2 of the ICAM-1 gene. An A --> T transversion in codon 29 of ICAM-1 exon 2 causes a lysine to methionine substitution (K29M), and was found at a high frequency (33.2%) in Kilifi (Kenya), as well as in other African populations. In this study we examined whether polymorphisms in exon 2 of ICAM-1 could be detected in a Caucasian population, assuming that these could be of importance in HRV binding. DNA from 100 healthy, unrelated, Belgian volunteers was obtained through a noninvasive swish-and-spit method. Using a primer set in the adjacent intron sequences, the full-length ICAM-1 exon 2 was amplified by polymerase chain reaction (PCR), followed by direct sequencing of the PCR product. No polymorphisms could be demonstrated in exon 2 of the ICAM-1 gene among all 100 tested individuals. The rhinovirus-binding Ig domain 1 of ICAM-1 seems to be a highly conserved region in the Caucasian population.

Base Sequence↗

Efficacy of inactivated and cold-adapted vaccines against influenza A infection, 1985 to 1990: the pediatric experience.

BACKGROUND: Influenza is a common and potentially serious infection in children. Although there is interest in broadening the use of influenza vaccine in healthy children, there are few large, randomized, controlled trials that evaluate the safety and efficacy of inactivated vaccine in the pediatric population. METHODS: From 1985 through 1990 a randomized, controlled trial of cold-adapted and inactivated vaccines for the prevention of influenza A disease was conducted at Vanderbilt University, and the cumulative results from this trial in patients of all ages have been previously published. We reanalyzed the data from this trial in the subset of patients who were younger than 16 years at the time of their participation. We determined vaccine safety, immunogenicity and efficacy, based on culture-positive illness and seroconversion, in this subset of patients. RESULTS: During the 5 years of the study, 791 children younger than 16 years received 1809 doses of either inactivated or cold-adapted vaccine or placebo. The vaccines were well-tolerated, and there were no serious reactions. Inactivated trivalent influenza vaccines were 91.4 and 77.3% efficacious in preventing symptomatic, culture-positive influenza A H1N1 and H3N2 illness, respectively. The efficacy of the inactivated vaccine based on hemagglutination inhibition assay seroconversion was 67.1 and 65.5%, respectively, for H1N1 and H3N2 serotypes. CONCLUSIONS: Inactivated trivalent influenza A vaccines are well-tolerated and efficacious in the prevention of influenza A disease in children 1 to 16 years old.

Adolescent↗

Statistical procedures for estimating the community probability of illness in family studies: rhinovirus and influenza.

A statistical method is presented for determining acquisition rates of illness from community sources of infection and for distinguishing among viruses which are associated with different epidemic seasons. The new method consists of a computationally simple procedure for estimating the community transmission parameter and the standard error of the estimator. This method, as well as a previously developed maximum likelihood procedure, is applied to illness data as a means for distinguishing among broad patterns of illness acquisition. The periods evaluated are the rhinovirus, influenza A and influenza B seasons in Tecumseh, Michigan, for the years 1976-1980. Tecumseh households are stratified into exposure groups depending on age-group composition. Estimates are found for the risk differences of illness acquired from the community for households with different age-group distributions. Analysis of the Tecumseh data reveals that members of households with children are more apt than members of households without children to acquire illness associated with rhinovirus, influenza A and influenza B from the community. Members of households with just preschool children (and adults) are more apt than members of households with just school children (and adults) to acquire illness associated with rhinovirus and influenza B from the community. In contrast, members of households with just preschool children (and adults) are just as likely as members of households with just school children (and adults) to acquire illnesses associated with influenza A from the community.

Adolescent↗

Effect of experimental rhinovirus 16 colds on airway hyperresponsiveness to histamine and interleukin-8 in nasal lavage in asthmatic subjects in vivo.

BACKGROUND: Asthma exacerbations are closely associated with respiratory virus infections. However, the pathophysiological consequences of such infections in asthma are largely unclear. OBJECTIVE: To examine the effect of rhinovirus 16 (RV16) infection on airway hypersensitivity to histamine, and on interleukin-8 (IL-8) in nasal lavage. METHODS: Twenty-seven non-smoking atopic, mildly asthmatic subjects participated in a placebo-controlled, parallel study. A dose of 0.5-2.9 x 10(4) TCID50 RV16 or placebo was nasally administered. Cold symptoms were recorded by questionnaire throughout the study. Histamine challenges were performed at entry, and on days 4 and 11 after inoculation. Nasal lavages were obtained at entry, and on days 2 and 9. The response to histamine was measured by PC20 (changes expressed as doubling doses: DD) IL-8 levels were obtained by ELISA, and were expressed in ng/ml. RESULTS: RV infection was confirmed by culture of nasal lavage and/or by antibody titre rise in each of the RV16-treated subjects. Among the 19 RV 16-treated subjects, eight developed severe cold symptoms. Baseline FEV1, did not change significantly during the study in either treatment group (P = 0.99). However, in the RV16-treated subjects there was a decrease in PC20 at day 4, which was most pronounced in those with a severe cold (mean change +/- SEM: -1.14 +/- 0.28 DD, P = 0.01). In addition, IL-8 levels increased in the RV16 group at days 2 and 9 (P < 0.001). The increase in nasal IL-8 at day 2 correlated significantly with the change in PC20 at day 4 (r = -0.48, P = 0.04). CONCLUSION: We conclude that the severity of cold, as induced by experimental RV16 infection, is a determinant of the increase in airway hypersensitivity to histamine in patients with asthma. Our results suggest that this may be mediated by an inflammatory mechanism, involving the release of chemokines such as IL-8.

Adolescent↗