Asthma is believed to be a risk factor for influenza infection, however little experimental evidence exists to directly demonstrate the impact of asthma on susceptibility to influenza infection. Using a mouse model, we now report that asthmatic mice are actually significantly more resistant to a lethal influenza virus challenge. Notably, the observed increased resistance was not attributable to enhanced viral clearance, but instead, was due to reduced lung inflammation. Asthmatic mice exhibited a significantly reduced cytokine storm, as well as reduced total protein levels and cytotoxicity in the airways, indicators of decreased tissue injury. Further, asthmatic mice had significantly increased levels of TGF-β1 and the heightened resistance of asthmatic mice was abrogated in the absence of TGF-β receptor II. We conclude that a transient increase in TGF-β expression following acute asthma can induce protection against influenza-induced immunopathology.

The analytical performance of the AIX1000 system, a fully automated and recently FDA-cleared rapid plasma reagin (RPR) system, was evaluated by comparison to a manual RPR test in a traditional syphilis testing algorithm. A total of 1,028 consecutive serum samples submitted for syphilis testing to the University of North Carolina Hospitals Clinical Immunology Laboratory were tested per each manufacturer's instructions. Among those samples, 996 were nonreactive and 20 were reactive using both the ASI RPR card system and the AIX1000 system. Of the 12 discrepant specimens, 11 were AIX1000 reactive and ASI card nonreactive whereas 1 specimen was ASI card reactive and AIX1000 nonreactive. The sensitivity and specificity of the manual ASI card were 76.0% and 99.8%, respectively, while the sensitivity and specificity of the AIX100 were 100.0% and 99.4%, respectively (sensitivity = 0.03). Among the 20 concordant reactive specimens, 68.4% of the titers agreed within ±1 dilution between methods. Reproducibility testing of the AIX1000 system demonstrated qualitative and semiquantitative (within ±1 dilution) agreement between specimens tested on different days of 96.0% and 76.0%, respectively, and 100.0% agreement between replicates within the same run. One of 24 samples analyzed under other disease conditions was reactive on both the AIX1000 system and the ASI card. Overall, the fully automated AIX1000 system demonstrated significantly enhanced sensitivity and specificity similar to that of the manual ASI RPR card test, making the AIX1000 system suitable for the laboratory diagnosis of syphilis in a clinical laboratory setting.

Asthma was the most common comorbidity observed among patients hospitalized with influenza A virus during the 2009 pandemic. However, little remains known about how the asthmatic phenotype influences protective immune responses against respiratory viral pathogens. Using the ovalbumin-induced allergic lung inflammation model, we found that asthmatic mice, unlike nonasthmatic mice, were highly susceptible to secondary heterologous virus challenge. While primary virus infection generated protective memory immune responses against homologous secondary virus challenge in both asthmatic and nonasthmatic mice, full protection against heterologous A/California/04/2009 (CA04) viral infection was observed only in nonasthmatic mice. Significant reductions in CA04-specific IgA, IgG, and IgM levels and in CA04-neutralizing activity of bronchoalveolar lavage fluid (BALF) was observed following secondary CA04 challenge of PR8-immunized asthmatic mice. Furthermore, transfer of immune BALF obtained from nonasthmatic, but not asthmatic, donors following secondary viral infection generated protection against CA04 in naive recipients. Nonspecific B-cell activation by CpG inoculation restored protection in PR8-immunized, CA04-challenged asthmatic mice. These results demonstrate a causal link between defective mucosal antibody responses and the heightened susceptibility of asthmatic mice to influenza infection and provide a mechanistic explanation for the observation that asthma was a major risk factor during the 2009 influenza pandemic. IMPORTANCEThe prevalence of asthma worldwide is increasing each year. Unfortunately, there is no cure for asthma. Asthmatic individuals not only suffer from consistent wheezing and coughing but are also believed to be more prone to serious lung infections that result in bronchitis and pneumonia. However, little is known about the influence of asthma on host mucosal immunity. Here we show that antibody responses during secondary heterologous influenza infections are suboptimal and that this is responsible for the increased mortality in asthmatic mice from viral infections. Understanding the mechanism of increased susceptibility will aid in developing new antiviral therapies for asthmatic patients.

Asthma is generally thought to confer an increased risk for invasive pneumococcal disease (IPD) in humans. However, recent reports suggest that mortality rates from IPD are unaffected in patients with asthma and that chronic obstructive pulmonary disease (COPD), a condition similar to asthma, protects against the development of complicated pneumonia. To clarify the effects of asthma on the subsequent susceptibility to pneumococcal infection, ovalbumin (OVA)-induced allergic lung inflammation (ALI) was induced in mice followed by intranasal infection with A66.1 serotype 3 Streptococcus pneumoniae. Surprisingly, mice with ALI were significantly more resistant to lethal infection than non-ALI mice. The heightened resistance observed following ALI correlated with enhanced early clearance of pneumococci from the lung, decreased bacterial invasion from the airway into the lung tissue, a blunted inflammatory cytokine and neutrophil response to infection, and enhanced expression of transforming growth factor ␤1 (TGF-␤1). Neutrophil depletion prior to infection had no effect on enhanced early bacterial clearance or resistance to IPD in mice with ALI. Although eosinophils recruited into the lung during ALI appeared to be capable of phagocytizing bacteria, neutralization of interleukin-5 (IL-5) to inhibit eosinophil recruitment likewise had no effect on early clearance or survival following infection. However, enhanced resistance was associated with an increase in levels of clodronatesensitive, phagocytic SiglecF low alveolar macrophages within the airways following ALI. These findings suggest that, while the risk of developing IPD may actually be decreased in patients with acute asthma, additional clinical data are needed to better understand the risk of IPD in patients with different asthma phenotypes. Streptococcus pneumoniae is a Gram-positive, extracellular bacterium commonly found in the upper respiratory tract and is recognized as the leading cause of community-acquired pneumonia worldwide (1). S. pneumoniae infections can range from asymptomatic carriage to more-severe outcomes such as otitis media, pneumonia, and pneumococcal meningitis. The capacity for invasion from a carrier state is directly related to the capsule polysaccharide serotype. Over 90 serotypes are known to exist (2), which complicates the clinical effectiveness of vaccination and emphasizes the importance of developing a better understanding of the immunological response to acute pneumococcal infections in the lung.Mortality following invasive pneumococcal infections is significantly higher among at-risk populations, such as the elderly or individuals with underlying medical conditions (3). Asthma has recently been identified as a significant risk factor for invasive pneumococcal disease (4-6). This increased risk has also been extended to other atopic conditions such as allergic rhinitis and hay fever (7), and the Advisory Committee on Immunization Practices has included individuals with asthma among those indicated for pneumococcal polysaccharid...