Experimental rhinovirus challenges in adults with mild asthma: response to infection in relation to IgE.

BACKGROUND: Although most children and young adults with asthma are atopic, exacerbations of asthma are frequently associated with viral respiratory tract infections, especially those caused by rhinovirus (HRV). OBJECTIVE: Young atopic adults with mild asthma were evaluated before and during an experimental HRV infection to test the hypothesis that airway inflammation before virus inoculation may be a risk factor for an adverse response to HRV. METHODS: Experimental HRV infections were evaluated in 16 allergic volunteers with mild asthma and 9 nonatopic control patients (age, 18 to 30 years). Before virus inoculation, each participant was screened with tests for lung function, prick skin tests for sensitization to common aeroallergens, measurements of total serum IgE, and serum neutralizing antibody to rhinovirus-16 (the serotype used for inoculation). The response to infection was monitored for 21 days by using symptom diary cards, tests for lung function, and markers of airway inflammation in nasal washes, blood, and expired air. RESULTS: During the infection, asthmatic patients had cumulative upper and lower respiratory tract symptom scores that were significantly greater over the course of 21 days than scores from the control patients. At baseline, the asthmatic patients also had increased sensitivity to methacholine and significantly lower values for FEV(1) (percent predicted) than the control patients (geometric mean and intraquartile values: 87% [79% to 91%] for the asthmatic patients and 101% [90% to 104%] for the control patients, P <.03). Among the patients with mild asthma, 6 had levels of total serum IgE that were substantially elevated (range, 371 to 820 IU/mL) compared with 10 who had lower levels (range, 29 to 124 IU/mL). Those with high levels of IgE had significantly greater lower respiratory tract symptom scores during the initial 4 days of the infection than the low IgE group. They also had higher total blood eosinophil counts at baseline, increased eosinophil cationic protein in their nasal washes (>200 ng/mL), and augmented levels of expired nitric oxide at baseline and during peak cold symptoms. In contrast, levels of soluble intracellular adhesion molecule-1 in nasal wash supernatants from the asthmatic patients with high IgE were diminished, both at baseline and during the infection. CONCLUSIONS: The reduced lung function and increased markers of inflammation observed before virus inoculation in the asthmatic patients who had high levels of total serum IgE may be risk factors for an adverse response to infections with HRV.

Imaging the lungs in asthmatic patients by using hyperpolarized helium-3 magnetic resonance: assessment of response to methacholine and exercise challenge.

BACKGROUND: Imaging of gas distribution in the lungs of patients with asthma has been restricted because of the lack of a suitable gaseous contrast agent. Hyperpolarized helium-3 (HHe3) provides a new technique for magnetic resonance imaging of lung diseases. OBJECTIVE: We sought to investigate the use of HHe3 gas to image the lungs of patients with moderate or severe asthma and to assess changes in gas distribution after methacholine and exercise challenge. METHODS: Magnetic resonance imaging was performed in asthmatic patients immediately after inhalation of HHe3 gas. In addition, images were obtained before and after methacholine challenge and a standard exercise test. RESULTS: Areas of the lung with no signal or sharply reduced HHe3 signal (ventilation defects) are common in patients with asthma, and the number of defects was inversely related to the percent predicted FEV(1) (r = 0.71, P <.002). After methacholine challenge (n = 3), the number of defects increased. Similarly, imaging of the lungs after exercise (n = 6) showed increased ventilation defects in parallel with decreases in FEV(1). The increase in defects after challenge in these 9 asthmatic patients was significant both for the number (P <.02) and extent (P <.02) of the defects. The variability and speed of changes in ventilation and the complete lack of signal in many areas is in keeping with a model in which the defects result from airway closure. CONCLUSION: HHe3 magnetic resonance provides a new technique for imaging the distribution of inhaled air in the lungs. The technique is suitable for following responses to treatment of asthma and changes after methacholine or exercise challenge.