Asthma prevalence and control among schoolchildren residing near outdoor air pollution sites.

INTRODUCTION: Outdoor air pollution (OAP) contributes to poor asthma outcomes and remains a public health concern in Pittsburgh. The purpose of this study was to determine the prevalence of childhood asthma and its rate of control among Pittsburgh schoolchildren residing near OAP sites. METHODS: Participants were recruited from schools near OAP sites. Asthma prevalence and control were assessed using a validated survey. Demographics and socioeconomic status were collected by survey, BMI was calculated, secondhand smoke (SHS) exposure was assessed by salivary cotinine levels, and OAP was assessed by mobile platform monitoring. Multivariate analysis adjusted for confounders. RESULTS: In 1202 Pittsburgh elementary school students surveyed, 50.9% were female, average age was 8.5 years (SD = 1.9), 52.2% were African American and 60.6% had public health insurance. SHS exposure was relatively high at 33.9%, 17.1% of students were obese, and 70% had exposure to particulate matter (PM2.5) greater than the World Health Organization standard of 10 µg/m3. Overall prevalence of asthma was 22.5% with PM2.5, nitric oxide (NOx), sulfur (S), and zinc (Zn) significantly related to odds of asthma. Among the 270 children previously diagnosed with asthma, 59.3% were not well controlled with PM2.5, black carbon, and silicon (Si) significantly related to odds of uncontrolled asthma. CONCLUSIONS: These results demonstrate that asthma prevalence and poor disease control are significantly elevated in Pittsburgh schoolchildren exposed to high levels of OAP. Future efforts need to focus on primary prevention of asthma by reducing exposure to OAP in at risk populations.

A Pilot Study of the Effect of an Educational Web Application on Asthma Control and Medication Adherence.

BACKGROUND: An Asthma Adherence Pathway (AAP) application, which is an Internet application that combines patient and clinician education strategies to promote adherence to asthma therapy, has been developed. OBJECTIVE: The primary objective of this pilot study was to evaluate the effectiveness of the AAP application with electronic adherence monitors on asthma control. Secondary objectives evaluated the effect of AAP and monitors on medication adherence, asthma symptoms, quality of life, psychosocial factors, and barriers to treatment. METHODS: Adult patients with asthma were randomly assigned either to intervention (n = 19) or control (n = 20) groups in this 3-month prospective study, and they completed the Asthma Control Questionnaire (ACQ). Intervention patients completed the AAP software and were given barrier-specific motivational interviewing adherence strategies and a SmartTrack device to monitor mometasone furoate/formoterol (MF/F) use. Clinicians in the interventional group received adherence management training. Interventional patients were given feedback regarding adherence findings at each visit. Treatment adherence was determined by the mean of 4 measures of doses taken over 3 months. Control patients were not monitored for MF/F adherence. RESULTS: The mean MF/F adherence in the intervention group was 81%. The intervention and control groups did not differ on the mean baseline ACQ. Thirteen intervention patients achieved the minimal important difference (defined as an improvement ≥0.5 units on the ACQ) compared with 6 control patients (P = .016). The intervention group showed greater improvement in the ACQ (0.75) than the control group (0.19) representing a moderate-to-large effect size of d = 0.638. CONCLUSIONS: The AAP was effective in promoting adherence and helped to improve asthma control. These findings provide preliminary validation of the AAP model.

Quintupling Inhaled Glucocorticoids to Prevent Childhood Asthma Exacerbations.

BACKGROUND: Asthma exacerbations occur frequently despite the regular use of asthma-controller therapies, such as inhaled glucocorticoids. Clinicians commonly increase the doses of inhaled glucocorticoids at early signs of loss of asthma control. However, data on the safety and efficacy of this strategy in children are limited. METHODS: We studied 254 children, 5 to 11 years of age, who had mild-to-moderate persistent asthma and had had at least one asthma exacerbation treated with systemic glucocorticoids in the previous year. Children were treated for 48 weeks with maintenance low-dose inhaled glucocorticoids (fluticasone propionate at a dose of 44 µg per inhalation, two inhalations twice daily) and were randomly assigned to either continue the same dose (low-dose group) or use a quintupled dose (high-dose group; fluticasone at a dose of 220 µg per inhalation, two inhalations twice daily) for 7 days at the early signs of loss of asthma control ("yellow zone"). Treatment was provided in a double-blind fashion. The primary outcome was the rate of severe asthma exacerbations treated with systemic glucocorticoids. RESULTS: The rate of severe asthma exacerbations treated with systemic glucocorticoids did not differ significantly between groups (0.48 exacerbations per year in the high-dose group and 0.37 exacerbations per year in the low-dose group; relative rate, 1.3; 95% confidence interval, 0.8 to 2.1; P=0.30). The time to the first exacerbation, the rate of treatment failure, symptom scores, and albuterol use during yellow-zone episodes did not differ significantly between groups. The total glucocorticoid exposure was 16% higher in the high-dose group than in the low-dose group. The difference in linear growth between the high-dose group and the low-dose group was -0.23 cm per year (P=0.06). CONCLUSIONS: In children with mild-to-moderate persistent asthma treated with daily inhaled glucocorticoids, quintupling the dose at the early signs of loss of asthma control did not reduce the rate of severe asthma exacerbations or improve other asthma outcomes and may be associated with diminished linear growth. (Funded by the National Heart, Lung, and Blood Institute; STICS ClinicalTrials.gov number, NCT02066129 .).

Acetaminophen versus Ibuprofen in Young Children with Mild Persistent Asthma.

BACKGROUND: Studies have suggested an association between frequent acetaminophen use and asthma-related complications among children, leading some physicians to recommend that acetaminophen be avoided in children with asthma; however, appropriately designed trials evaluating this association in children are lacking. METHODS: In a multicenter, prospective, randomized, double-blind, parallel-group trial, we enrolled 300 children (age range, 12 to 59 months) with mild persistent asthma and assigned them to receive either acetaminophen or ibuprofen when needed for the alleviation of fever or pain over the course of 48 weeks. The primary outcome was the number of asthma exacerbations that led to treatment with systemic glucocorticoids. Children in both groups received standardized asthma-controller therapies that were used in a simultaneous, factorially linked trial. RESULTS: Participants received a median of 5.5 doses (interquartile range, 1.0 to 15.0) of trial medication; there was no significant between-group difference in the median number of doses received (P=0.47). The number of asthma exacerbations did not differ significantly between the two groups, with a mean of 0.81 per participant with acetaminophen and 0.87 per participant with ibuprofen over 46 weeks of follow-up (relative rate of asthma exacerbations in the acetaminophen group vs. the ibuprofen group, 0.94; 95% confidence interval, 0.69 to 1.28; P=0.67). In the acetaminophen group, 49% of participants had at least one asthma exacerbation and 21% had at least two, as compared with 47% and 24%, respectively, in the ibuprofen group. Similarly, no significant differences were detected between acetaminophen and ibuprofen with respect to the percentage of asthma-control days (85.8% and 86.8%, respectively; P=0.50), use of an albuterol rescue inhaler (2.8 and 3.0 inhalations per week, respectively; P=0.69), unscheduled health care utilization for asthma (0.75 and 0.76 episodes per participant, respectively; P=0.94), or adverse events. CONCLUSIONS: Among young children with mild persistent asthma, as-needed use of acetaminophen was not shown to be associated with a higher incidence of asthma exacerbations or worse asthma control than was as-needed use of ibuprofen. (Funded by the National Institutes of Health; AVICA ClinicalTrials.gov number, NCT01606319.).

The Future of Sublingual Immunotherapy in the United States.

Sublingual immunotherapy (SLIT) is a safe and effective treatment for allergic rhinitis (AR) and allergic rhinoconjunctivitis (ARC). The Food and Drug Administration (FDA) in the USA has approved three SLIT tablets for the treatment of AR and ARC in relation to pollen. Specifically, Grastek® and Oralair® are two formulations approved to treat patients suffering with AR/ARC to grass pollen, and Ragwitek™ is a formulation approved to treat patients suffering with AR/ARC to ragweed pollen. Although these approvals provide support for physicians to prescribe SLIT, barriers to prescribing SLIT still remain such as FDA approval for additional formulations, a standard dose and dosing schedule, and cost/insurance coverage. In order to further support the use of SLIT, research is currently being conducted to expand the indication for SLIT to other common comorbidities to AR/ARC. For example, allergic asthma, food allergies, and atopic dermatitis are other diseases which are being explored. The future of SLIT in the USA is unknown; however, education will be necessary for both providers and patients.

An asthma sports camp series to identify children with possible asthma and cardiovascular risk factors.

BACKGROUND: The prevalence of asthma and obesity in children has increased over the past several years, with obesity being associated with higher rates of asthma. In response to known disparities in asthma prevalence and morbidity, along with barriers to diagnosis, assessment and education, a comprehensive asthma sports camp series was developed and implemented. OBJECTIVE: The primary objective was to evaluate the effectiveness of utilizing a sports camp model to identify children with undiagnosed and uncontrolled asthma, and to provide recommendations for follow-up care. The secondary objectives were to identify the presence of and associations between related co-morbidities and risk factors for asthma morbidity such as obesity, hypertension and exposure to tobacco smoke; and to assess asthma medication use. METHODS: Six daylong camps at an inner-city university were offered to children 5-17 years of age over a period of two years. Asthma, body mass index, blood pressure (BP) and carbon monoxide screenings were conducted at each camp. RESULTS: In this sample, 43.7% of children had previously diagnosed asthma, and 12.6% were classified as having potential, undiagnosed asthma. Of the children with previously diagnosed asthma, 76% were considered uncontrolled. Thirty-eight percent were determined to be overweight or obese and 17% had elevated BP. CONCLUSIONS: An interdisciplinary sports camp model can be used to identify children with undiagnosed and uncontrolled asthma and cardiovascular risk factors; and to provide recommendations for follow-up care.

Impact of student pharmacist-delivered asthma education on child and caregiver knowledge.

OBJECTIVE: To evaluate the effectiveness of asthma education delivered by student pharmacists and to assess the impact of child and caregiver baseline asthma knowledge on asthma control in children. DESIGN: Student pharmacists developed and implemented asthma self-management education interventions for children and their caregivers and performed asthma screenings for children at a series of asthma camps. ASSESSMENT: Eighty-seven children, ages 5-17 years, and their caregivers were enrolled in this study. A previously validated asthma questionnaire was modified to assess asthma knowledge among children and adults. Asthma knowledge increased significantly in children following participation in the education intervention (p<0.001). The education intervention, however, did not increase caregiver knowledge of asthma. A significant association was observed between caregiver baseline asthma knowledge and better asthma control in their children (p=0.019). CONCLUSION: The results of this study demonstrate that student pharmacist-delivered asthma education can positively impact asthma knowledge in children, and that caregivers' knowledge of asthma is strongly correlated with better asthma control in their children.

New asthma drugs: small molecule inhaled corticosteroids.

Small-particle inhaled corticosteroid (ICS) metered-dose inhalers were recently developed to treat asthma as part of the CFC to HFA propellant switch mandated by the Montreal Protocol. Two such ICS, beclomethasone dipropionate (BDP) and ciclesonide (CIC), are available in the United States and are formulated in HFA solutions. A major advantage of small-particle ICS is that they have improved total lung deposition and consequently, effective asthma control is achieved at lower daily doses than the large-particle ICS. Another advantage of small-particle ICS is that they are able to reach the small airways and consequently, may result in increased efficacy. Indeed, recent studies have demonstrated the effect of small-particle ICS on asthmatic inflammation in the small airways. Another advantage of small-particle ICS is that they may have an improved safety profile. Small-particle inhalers generally deposit decreased amounts of drug in the oropharynx than their CFC counterparts possibly resulting in a lower incidence of oropharyngeal candidiasis. However, growth studies and most HPA studies do not support improved safety on the basis of particle size alone and some studies suggest even higher systemic bioavailability and safety risk with smaller particles, depending on the molecule and the formulation. Further efficacy and safety studies are clearly warranted to determine any potential advantages of small-particle ICS, particularly in long-term disease modification where large-particle ICS have failed, and in infants and pre-schoolers, in whom airway delivery is problematic with current formulations.

Effect of therapeutic doses of mometasone furoate on cortisol levels in children with mild asthma.

Corticosteroids are the foundation of pharmacologic treatment for children with asthma. However, high-dose inhaled corticosteroid treatment can cause hypothalamic-pituitary-adrenal (HPA) axis suppression. We investigated the effect of three doses of mometasone furoate administered via dry-powder inhaler (MF-DPI) on the HPA axis in children. Fifty children (6-11 years) with mild asthma of > or =6 months' duration were randomized to MF-DPI, 100 (n = 13), 200 (n = 13), or 400 micrograms b.i.d. (n = 12), or placebo (n = 12) for 29 days. The primary end point was change from baseline in the 12-hour area under the plasma-cortisol-concentration-time curve (AUC). Secondary parameters included plasma cortisol response to cosyntropin stimulation and 24-hour urinary free cortisol concentrations. Compared with placebo, AUC changes associated with treatments of MF-DPI, 100 or 200 micrograms b.i.d., were not significant, whereas a significant change was observed with MF-DPI, 400 micrograms b.i.d. (27%; p = 0.05). Responses to cosyntropin stimulation and urinary cortisol measurements were similar to placebo with all MF-DPI doses. All regimens were well tolerated. MF-DPI did not have a significant effect on plasma or urinary cortisol levels at doses up to 200 micrograms b.i.d. in children with mild asthma. Higher MF-DPI doses may potentially suppress the HPA axis.

Effect on growth of long-term treatment with intranasal triamcinolone acetonide aqueous in children with allergic rhinitis.

BACKGROUND: Guidelines recommend treatment with intranasal corticosteroids for patients with allergic rhinitis (AR), but concerns remain about possible adverse effects. OBJECTIVE: To present the 1- and 2-year growth results for children with AR treated with triamcinolone acetonide aqueous nasal spray. METHODS: Thirty-nine children (aged 6.1-14.3 years at study entry) were treated with triamcinolone acetonide aqueous for 1 year, and a subset of 30 children completed a second year of treatment. The dose was physician titered to achieve control over AR symptoms. For each child, statural heights at baseline and at the 1- and 2-year (where available) visits, together with growth rates, were measured and were compared with predicted values. RESULTS: There were no significant differences between measured and predicted heights at the 1- and 2-year visits. The mean (SD) measured--predicted difference was 0.3 (2.2) cm (95% confidence interval, -0.4 to 1.0 cm) at the 1-year visit and 0.5 (3.0) cm (95% confidence interval, -0.6 to 1.6 cm) at the 2-year visit. Mean differences in measured and predicted growth rates were nonsignificant at the 1- and 2-year visits. CONCLUSIONS: Triamcinolone acetonide aqueous titered to control AR symptoms and given for 1 or 2 years had no significant effect on statural growth in children with AR.

A randomized, double-blind, parallel-group, multicenter, placebo-controlled study of the safety and efficacy of extended-release guaifenesin/pseudoephedrine hydrochloride for symptom relief as an adjunctive therapy to antibiotic treatment of acute respiratory infections.

PURPOSE: This study assessed the efficacy and safety of guaifenesin 600 mg and pseudoephedrine hydrochloride 60 mg extended-release bilayer tablets in providing relief of acute respiratory symptoms when used as an adjunct to antibiotics in patients with an acute respiratory infection (ARI). METHODS: Adult patients experiencing symptoms of ARI and meeting the physician's usual diagnostic criteria for oral antibiotic treatment were prescribed an antibiotic and randomized to adjunctive guaifenesin/pseudoephedrine hydrochloride or matching placebo twice daily for 7 days. Patients completed symptom diaries and treatment assessments twice daily and attended office visits on Days 4 and 8. RESULTS: The safety/intent-to-treat (ITT) population analysis included 601 patients (guaifenesin/pseudoephedrine, n = 303; placebo, n = 298). Mean symptom scores were lower with guaifenesin/pseudoephedrine from Day 3 for every symptom assessed, with statistically significant improvements in total symptom score from Day 3 (P = 0.026). The greatest effects of treatment with guaifenesin/pseudoephedrine were observed for nasal congestion and sinus headache. Time to overall relief was shorter with guaifenesin/pseudoephedrine (P = 0.038). Significantly more patients reported "the medication was helping during the day" on Day 2 with guaifenesin/pseudoephedrine (P = 0.002). Patient assessments of symptom relief showed a significant preference for guaifenesin/pseudoephedrine versus placebo (P = 0.021). Treatment with guaifenesin/pseudoephedrine was well tolerated. Insomnia (2.6%), nausea (2.3%), and headache (1.3%) were the most common treatment-related adverse effects. CONCLUSIONS: As adjunctive therapy for symptom relief for patients taking antibiotics for ARIs, guaifenesin/pseudoephedrine shortened time to relief and improved bothersome respiratory symptoms better than placebo, with greatest effects seen for nasal congestion and sinus headache.

Viral and bacterial rhinitis.

In contradistinction to the poetically inspired disjunction between the name and quality of a rose recited by Juliet in the famous quote from Shakespeare's play, disease labels used in the medical sciences need to have exact meaning to ensure that they communicate an accurate diagnosis and a valid treatment approach. Above, we presented a consistent nosology for rhinitis consequent to infection. There, we argued that the term "rhinitis" should be used to describe the condition of nasal mucosal pathology and that the rSSC be used to describe the appreciated expression of that pathology. In discussing viral and bacterial rhinitis, we conclude that former is consistent with a strict application of our nosology where the accompanying rSSC is usually referred to as cold or flu, but that the latter is not. Lacking direct evidence for bacterial infection of the nasal mucosa, bacterial rhinitis is better referred to as an acute bacterial infection of an adjacent compartment complicated by rhinitis (e.g., sinusitis complicated by rhinitis) or as "toxic rhinitis" complicated by bacterial infection. Interestingly, bacterial infection of the adjacent compartments is a frequent complication of viral rhinitis making "bacterial" rhinitis a complication of a complication of viral rhinitis. The antiviral and antibacterial host-defense mechanisms available to the nasal mucosa are multilayered and formidable. For this reason, nasal mucosal infection with extracellular bacterial pathogens is rarely established and infection with a broad range of upper respiratory viruses is self-limited with short duration morbidity and no mortality. However, in select subpopulations, those infections predispose to more serious complications associated with secondary bacterial, and perhaps viral, infection of the sinuses, middle ears, and lungs. The morbidity and mortality of these complications remains a concern, and strategies to decrease their frequency need to be formulated and tested in clinical trials. Because the viruses causing rhinitis are spread by interpersonal contact, the most appropriate and least expensive prophylactic measures are good hygiene and contact avoidance. Prophylactic efficacy for vaccination and passive immunoglobulin therapy was demonstrated for influenza and RSV infections, respectively. However, these approaches hold little promise for other viruses and are associated with some risks, making them less acceptable for populations "at low risk" for the more serious complications of viral rhinitis. Existing pharmacological treatments for viral rhinitis target the effector chemicals of the rSSC and therefore are largely palliative, whereas antiviral treatment has limited theoretical and realized efficacy, and no treatment has been shown to decrease the risk of complications. Indeed, given the small treatment window available (time between rSSC onset and typical resolution) and the poor understanding of the immune/inflammatory pathways of host defense, it is doubtful that the general population's demand for a cure will be satisfied in the near future, but then, viral rhinitis by any other name is still just a cold.

Allergy skin test responses during experimental infection with respiratory syncytial virus.

BACKGROUND: Allergy skin testing is one of the most frequently performed physician office procedures. Many factors can affect the results of those tests, including the well-defined suppressive effect of systemic antihistamines. False-positive allergen skin test results are known to occur; however, contributing factors are not well understood. OBJECTIVE: To determine whether a viral upper respiratory tract infection affects allergy skin test responsiveness. METHODS: We performed skin tests with histamine and a panel of geographically relevant inhalant allergens on 16 adults before and 3, 6, and 21 days after experimental exposure to respiratory syncytial virus (RSV), a virus that causes signs and symptoms of a cold. RESULTS: The RSV exposure, with and without documented infection, caused increased wheal and flare areas to histamine and allergen and de novo positive allergen test responses in individuals with no measurable responses at baseline. These were noted as late as 21 days after RSV exposure and may be consistent with mediation by up-regulated neurogenic inflammation during RSV infection. CONCLUSION: These results may have implications for explaining the cause of such well-known complications of RSV infection as otitis media, bronchiolitis, and asthmatic exacerbation.

Emotional style, nasal cytokines, and illness expression after experimental rhinovirus exposure.

Psychosocial factors moderate the expression of illness during upper respiratory virus infections but past attempts to define mediational pathways were not successful. Here, we used a model of experimental rhinovirus infection in humans to evaluate three proinflammatory cytokines for their potential role in mediating the previously documented association between positive emotional style and illness. After assessing emotional style in 327 healthy adults, each was exposed to one of two strains of rhinovirus and followed for 5 days in quarantine. Symptoms/signs, nasal lavage IL-1beta, IL-6, and IL-8 protein, and viral shedding were assessed at baseline and on each of the 5 days after exposure. Virus-specific antibody was assessed at baseline and 28 days after challenge. An analysis of the data for 234 subjects with documented infection showed that nasal IL-1beta, IL-6, and IL-8 protein levels were all associated with greater illness expression but IL-6 was by far the best predictor of nasal signs and symptoms. Lower positive emotional style was associated with greater objective and subjective markers of illness and these associations were decreased substantially by controlling for IL-6 but not for IL-1beta or IL-8. These results are consistent with the hypothesis that IL-6 acts as a biological mediator in linking positive emotional style to illness expression during rhinovirus infection.

Diminished dendritic cell interleukin 10 production in atopic children.

BACKGROUND: Diminished interleukin 10 (IL-10) and/or IL-12 production may contribute to the pathogenesis of asthma and atopy. Dendritic cells (DCs) produce these cytokines and have been implicated in the pathogenesis of these disorders. OBJECTIVE: To determine whether DC IL-10 and/or IL-12 production is diminished in children aged 6 to 12 years with allergic rhinitis (AR) and with or without asthma. METHODS: Monocyte-derived DCs were isolated from 20 subjects without AR or asthma (group 1), 20 subjects with AR without asthma (group 2), and 20 subjects with AR and asthma (group 3). Asthma was defined as a history of physician-diagnosed disease, and AR was defined as a positive history and positive puncture skin test responses (wheal > or = 5 mm) to relevant inhalant allergens. DCs were stimulated with either lipopolysaccharide (LPS) or diluent and cultured for 24 hours. Supernatants were assayed for IL-10 and IL-12 levels by enzyme-linked immunosorbent assay. RESULTS: DC IL-10 production was diminished in groups 2 and 3 compared with group 1. Median LPS-induced IL-10 levels were 11.0 pg/mL in group 1, 6.1 pg/mL in group 2, and 1.5 pg/mL in group 3. The frequencies of subjects with detectable IL-10 levels were 85%, 20%, and 20% in groups 1, 2 and 3, respectively. Median LPS-induced IL-12 levels were similar in all groups. CONCLUSIONS: These data support the hypothesis that atopic subjects have an intrinsic inability to up-regulate DC IL-10 production. Future studies in this area could lead to a better understanding of the pathogenesis of atopy.

Association between TNF-alpha and TGF-beta genotypes in infants and parental history of allergic rhinitis and asthma.

The development and expression of allergic rhinitis and asthma may be influenced by the elaboration of specific cytokines. Cytokine genotypes moderate illness severity in a variety of inflammatory disorders. Cytokine genotyping was performed on 124 infants (85% white, 57% male) to determine whether specific cytokine genotypes are associated with a parental history of allergic rhinitis and/or asthma. DNA was extracted from buccal brushings and assayed for tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), interleukin (IL)-6, IL-10, and transforming growth factor (TGF)-beta1 genotypes using polymerase chain reaction-sequence specific primer technology. Outcomes consisted of parental history of allergy and asthma, and results were evaluated by logistic regression. TNF-alpha and TGF-beta genotypes were related to maternal and/or paternal history of allergic rhinitis and asthma, respectively. The frequencies of the genotype associated with high production of TNF-alpha were 41% versus 18% in infants with and without a parental history of allergic rhinitis, respectively (p < 0.01). The frequencies of the genotype associated with low production of TGF-beta1 were 14% versus 1% in infants with and without a parental history of asthma, respectively (p < 0.01). There were no associations between IFN-gamma, IL-6, and IL-10 genotypes and any of the outcome parameters. These results suggest a role for TNF-alpha and TGF-beta1 genotypes in the pathogenesis of allergic rhinitis and asthma, respectively. If confirmed by future studies, cytokine genotyping may be a useful tool for identifying at-risk infants who may benefit from the selective use of preventative and/or early intervention treatments for these disorders.

Elevations of local leukotriene C4 levels during viral upper respiratory tract infections.

BACKGROUND: One potential mechanism by which respiratory viruses trigger illness and complications is via the local elaboration of inflammatory mediators. OBJECTIVE: To determine whether there is an increase in local leukotriene C4 (LTC4) levels during experimental infection with influenza A virus (FLU), rhinovirus (RV), or respiratory syncytial virus (RSV). METHODS: Healthy adults were intranasally inoculated with a safety-tested strain of FLU (n = 29), RV (n = 16), or RSV (n = 21). Nasal lavage samples were collected, symptoms were recorded, and expelled nasal secretions were weighed before and then daily after challenge. Lavage samples were submitted for viral culture and assayed for LTC4 levels by radioimmunoassay. Serum antibody titers to the challenge viruses were assayed at baseline and 21 days after challenge. RESULTS: All subjects were infected as evidenced by viral shedding and/or seroconversion. Following infection, significant increases (P < 0.05 by analysis of variance) in LTC4 levels were measured for each virus. Furthermore, there was a temporal association between the local LTC4 levels and the development of illness. CONCLUSIONS: The results of this study, which used an adult experimental model, demonstrate elevations in locally produced LTC4 during respiratory infection with FLU, RV, and RSV. Future studies using antileukotriene agents may help elucidate the precise role of leukotrienes in mediating disease expression.

Cytokine levels during symptomatic viral upper respiratory tract infection.

BACKGROUND: Previous studies suggest a role for locally produced proinflammatory cytokines in the development and expression of illness during experimental infection with a variety of respiratory viruses. However, most of these studies fail to make comparisons between symptomatic and asymptomatic infected subjects. OBJECTIVE: To compare the pattern of nasal cytokine elaboration in asymptomatic and symptomatic subjects experimentally infected with rhinovirus-39 (RV-39). METHODS: Healthy adults underwent experimental intranasal inoculation with a safety-tested clinical isolate of RV-39. Nasal lavages were collected, nasal symptoms were recorded, and expelled nasal secretions were weighed before and then daily for 6 days after challenge. Nasal lavages were submitted for viral culture and assayed for cytokine protein levels by enzyme-linked immunosorbent assay. RESULTS: Twenty-nine subjects were enrolled in the study. All subjects were infected as evidenced by viral shedding and/or seroconversion. Sixteen subjects were symptomatic and 13 were asymptomatic as evaluated by subject self-report. During infection, significant increases in mean levels of nasal interleukin 6 (IL-6) (P = .01) and IL-1 (P = .02) were observed in symptomatic but not asymptomatic subjects. In symptomatic subjects, these increases were temporally related to the development of nasal symptoms and production of secretions. Mean levels of IL-8, IL-10, and tumor necrosis factor a were not increased in either group during infection. CONCLUSIONS: The results of this study demonstrate elevations in certain locally produced cytokines during symptomatic but not asymptomatic respiratory infection with RV-39. Future studies using selected anticytokine therapies may help elucidate the precise role of cytokines in mediating disease expression.