Development of a Rhinovirus Inoculum Using a Reverse Genetics Approach.

Background: Experimental inoculation is an important tool for common cold and asthma research. Producing rhinovirus (RV) inocula from nasal secretions has required prolonged observation of the virus donor to exclude extraneous pathogens. We produced a RV-A16 inoculum using reverse genetics and determined the dose necessary to cause moderate colds in seronegative volunteers.

Effects of montelukast on patients with asthma after experimental inoculation with human rhinovirus 16.

Background: Leukotrienes are induced by viral infections.

Objectives: To determine whether treatment with montelukast would improve asthma disease control in patients with mild allergic asthma during an experimentally induced rhinovirus infection.

Methods: Patients with mild allergic asthma were randomized to receive treatment with either montelukast or placebo, and 7 days later both groups were inoculated with human rhinovirus 16.

House dust mite sublingual immunotherapy: results of a US trial.

Background: Few trials of sublingual immunotherapy (SLIT) in the United States have been reported.

Objective: This randomized, placebo-controlled feasibility SLIT study compared the safety and physiologic effects of high- versus low-dose Dermatophagoides farinae vaccine.

Methods: Thirty-one D farinae-sensitive adults with allergic rhinitis with or without mild intermittent asthma were eligible for randomization to high-dose maintenance vaccine (n = 10, 4200 allergen units [approximately 70 μg of Der f 1/d]), low-dose maintenance vaccine (n = 10; 60 allergen units [approximately 1 μg of Der f 1/d]), or placebo (n = 11) over 12 to 18 months.

Similar colds in subjects with allergic asthma and nonatopic subjects after inoculation with rhinovirus-16.

Background: Rhinovirus infections are frequent causes of asthma exacerbations.

Objective: This study was conducted to test whether subjects with and without allergic asthma have different responses to infection and to identify baseline patient risk factors that predict cold outcomes.

Methods: Twenty subjects with mild persistent allergic asthma and 18 healthy subjects were experimentally inoculated with rhinovirus-16.

Distribution and seasonality of rhinovirus and other respiratory viruses in a cross-section of asthmatic children in Trinidad, West Indies.

Background: Childhood asthma in the Caribbean is advancing in prevalence and morbidity. Though viral respiratory tract infections are reported triggers for exacerbations, information on these infections with asthma is sparse in Caribbean territories. We examined the distribution of respiratory viruses and their association with seasons in acute and stable asthmatic children in Trinidad.

A study to evaluate safety and efficacy of mepolizumab in patients with moderate persistent asthma.

Rationale: Accumulation of eosinophils in the bronchial mucosa of individuals with asthma is considered to be a central event in the pathogenesis of asthma. In animal models, airway eosinophil recruitment and airway hyperresponsiveness in response to allergen challenge are reduced by specific targeting of interleukin-5. A previous small dose-finding study found that mepolizumab, a humanized anti-interleukin-5 monoclonal antibody, had no effect on allergen challenge in humans.

Inhibition of rhinovirus replication in vitro and in vivo by acid-buffered saline.

Human rhinoviruses (HRVs) are quite sensitive to low pH. To determine whether this characteristic might be a therapeutic target, we evaluated the sensitivity of HRV to low-pH buffers in vitro and in vivo. Our findings confirm that low pH inhibited replication of most HRVs and reduced the replication of influenza virus.

Neural circuitry underlying the interaction between emotion and asthma symptom exacerbation.

Asthma, like many inflammatory disorders, is affected by psychological stress, suggesting that reciprocal modulation may occur between peripheral factors regulating inflammation and central neural circuitry underlying emotion and stress reactivity. Despite suggestions that emotional factors may modulate processes of inflammation in asthma and, conversely, that peripheral inflammatory signals influence the brain, the neural circuitry involved remains elusive. Here we show, using functional magnetic resonance imaging, that activity in the anterior cingulate cortex and insula to asthma-relevant emotional, compared with valence-neutral stimuli, is associated with markers of inflammation and airway obstruction in asthmatic subjects exposed to antigen.

Quantitative and qualitative analysis of rhinovirus infection in bronchial tissues.

Although rhinovirus (RV) infections can cause asthma exacerbations and alter lower airway inflammation and physiology, it is unclear how important bronchial infection is to these processes. To study the kinetics, location, and frequency of RV appearance in lower airway tissues during an acute infection, immunohistochemistry and quantitative polymerase chain reaction analysis were used to analyze the presence of virus in cells from nasal lavage, sputum, bronchoalveolar lavage, bronchial brushings, and biopsy specimens from 19 subjects with an experimental RV serotype 16 (RV16) cold. RV was detected by polymerase chain reaction analysis on cells from nasal lavage and induced sputum samples from all subjects after RV16 inoculation, as well as in 5 of 19 bronchoalveolar lavage cell samples and in 5 of 18 bronchial biopsy specimens taken 4 days after virus inoculation.

Rhinovirus-induced interferon-gamma and airway responsiveness in asthma.

The majority of asthma exacerbations are caused by respiratory infections, with rhinovirus (RV) being the most common virus. Recent evidence has suggested that decreased generation of IFN-gamma is associated with more severe colds and delayed elimination of virus. Whether the generation of IFN-gamma also has any relationship to general features of asthma severity has yet to be determined.

Comparison of the effects of repetitive low-dose and single-dose antigen challenge on airway inflammation.

Background: Airway allergen provocation provides a model to study allergic inflammation in relationship to pulmonary physiology. Allergen provocation is usually administered as a relatively large single-dose challenge that might not reflect a chronic, natural, low-dose airborne allergen exposure.

Objective: We sought to compare the magnitude, characteristic features, and kinetics of airway inflammation induced by means of repetitive low-dose antigen challenges with those factors induced by means of an equivalent single-dose allergen challenge in allergic asthma.

School examinations enhance airway inflammation to antigen challenge.

Psychological stress can lead to asthma exacerbations in some patients. It is our hypothesis that the stress effect can occur through an enhancement of allergic inflammatory response. To investigate this possibility, airway antigen challenge was evaluated in 20 college students with mild asthma during both a low-stress phase (midsemester or two weeks postfinal examination) and a stress phase (final examination week).