Exhausted and Apoptotic BALF T Cells in Proinflammatory Airway Milieu at Acute Phase of Severe Mycoplasma Pneumoniae Pneumonia in Children

AbstractHost immune response may be involved in the pathogenesis of children Mycoplasma pneumoniae pneumonia (MPP). In the current study, we investigated the alterations of cytokines levels among control, mild MPP and severe MPP children to determine whether cytokine signatures associate with MPP and correlate with disease severity. We measured 13 cytokines in bronchoalveolar lavage fluid (BALF) of 88 children with MPP and 26 children with foreign body aspiration (FB) using a Luminex system. Linear discriminant analyses were performed to develop predictive models of mild MPP and severe MPP on these children. We observed nearly complete separations of severe MPP group, mild MPP group and control group in linear discriminant analyses. Eleven cytokines significantly increased in children with MPP, and seven cytokines had statistically significant upward linear trends correlated with MPP severity. In addition, compared to control group, both IFNγ/IL4 ratio and IFNγ/IL13 ratio increased in mild MPP and severe MPP groups. Our results suggest that children MPP can alter BALF cytokines signatures which associate with disease severity and can be characterized by a distinct airway molecular phenotype that has elevated Th1/Th2 ratios.

Abstract Background: An increased number of refractory mycoplasma pneumoniae (MP) pneumonia (MPP) cases have been reported. However the duration of MP infection in lower airway and the course of anti-MP treatment remains unclear. Methods: We retrospectively reviewed the medical records of 94 MPP children. Patients were classified into two groups. The long-term group (Group LT) was defined as bronchoalveolar lavage fluid (BALF) remained MP-positive by PCR after 30 days of the disease course. The non-long-term group (Group NLT) was defined as BALF became MP-negative by PCR within 30 days of disease and patients who only needed one bronchoscopy lavage therapy. MP loads, clinical outcomes were analyzed along with other clinical measurements. Results: The average levels of inflammatory markers such as C reactive protein and lactate dehydrogenase in Group LT were significantly higher than those in Group NLT. Airway and lung damage in Group LT were more severe than Group NLT. 28 patients developed necrotizing pneumonia and 8 patients developed pulmonary embolism in Group LT. Mean maximum MP loads in BALF were 10 7.46±0.93 and 10 4.86±0.93 in Groups LT and NLT, respectively. There was persistent MP DNA in Group LT, even lasted for 120 days. One severe MPP patient in Group LT had MP-associated bloodstream infection. After 3 months of follow-up, chest imaging revealed incomplete absorption of pulmonary consolidation in 33 patients of Group LT [including 13 airway obliterans (AO) patients] and in 7 patients of Group NLT (including 2 AO patients). Conclusion: MP loads of BALF were associated with the subsequent duration of MP DNA in lower airway. High MP loads and persistent long-term MP DNA in lower airway were associated with severity of pediatric MPP.

Abstract Background An increased number of refractory mycoplasma pneumoniae (MP) pneumonia (MPP) cases have been reported. However the duration of MP infection in lower airway and the course of anti-MP treatment remains unclear. Methods We retrospectively reviewed the medical records of 94 MPP children. Patients were classified into two groups. The long-term group (Group LT) was defined as bronchoalveolar lavage fluid (BALF) remained MP-positive by PCR after 30 days of the disease course. The non-long-term group (Group NLT) was defined as BALF became MP-negative by PCR within 30 days of disease and patients who only needed one bronchoscopy lavage therapy. MP loads, clinical outcomes were analyzed along with other clinical measurements. Results The average levels of inflammatory markers such as C reactive protein and lactate dehydrogenase in Group LT were significantly higher than those in Group NLT. Airway and lung damage in Group LT were more severe than Group NLT. 28 patients developed necrotizing pneumonia and 8 patients developed pulmonary embolism in Group LT. Mean maximum MP loads in BALF were 107.46 ± 0.93 and 104.86 ± 0.93 in Groups LT and NLT, respectively. There was persistent MP DNA in Group LT, even lasted for 120 days. One severe MPP patient in Group LT had MP-associated bloodstream infection. After 3 months of follow-up, chest imaging revealed incomplete absorption of pulmonary consolidation in 33 patients of Group LT [including 13 airway obliterans (AO) patients] and in 7 patients of Group NLT (including 2 AO patients). Conclusion MP loads of BALF were associated with the subsequent duration of MP DNA in lower airway. High MP loads and persistent long-term MP DNA in lower airway were associated with severity of pediatric MPP.

Abstract Background: An increased number of refractory mycoplasma pneumoniae (MP) pneumonia (MPP) cases have been reported. However the duration of MP infection in lower airway and the course of anti-MP treatment remains unclear. Methods: We retrospectively reviewed the medical records of 94 MPP children. Patients were classified into two groups. The long-term group (Group LT) was defined as bronchoalveolar lavage fluid (BALF) remained MP-positive by PCR after 30 days of the disease course. The non-long-term group (Group NLT) was defined as BALF became MP-negative by PCR within 30 days of disease and patients who only needed one bronchoscopy lavage therapy. MP loads, clinical outcomes were analyzed along with other clinical measurements. Results: The average levels of inflammatory markers such as C reactive protein and lactate dehydrogenase in Group LT were significantly higher than those in Group NLT. Airway and lung damage in Group LT were more severe than Group NLT. 28 patients developed necrotizing pneumonia and 8 patients developed pulmonary embolism in Group LT. Mean maximum MP loads in BALF were 10 7.46±0.93 and 10 4.86±0.93 in Groups LT and NLT, respectively. There was persistent MP DNA in Group LT, even lasted for 120 days. One severe MPP patient in Group LT had MP-associated bloodstream infection. After 3 months of follow-up, chest imaging revealed incomplete absorption of pulmonary consolidation in 33 patients of Group LT [including 13 airway obliterans (AO) patients] and in 7 patients of Group NLT (including 2 AO patients). Conclusion: MP loads of BALF were associated with the subsequent duration of MP DNA in lower airway. High MP loads and persistent long-term MP DNA in lower airway were associated with severity of pediatric MPP.

ABSTRACT Mycoplasma pneumoniae is a major cause of community-acquired pneumonia. We evaluated the efficacy of LBM415, a novel peptide deformylase inhibitor antimicrobial agent, for the treatment of M. pneumoniae pneumonia in a mouse model. Eight-week-old BALB/c mice were intranasally inoculated once with 107 CFU of M. pneumoniae. Groups of mice were treated with LBM415 (50 mg/kg of body weight) or placebo subcutaneously daily for 13 days, starting 24 h after inoculation. Groups of mice were evaluated at the baseline; at days of treatment 1, 3, 6, and 13; and at 7 days after treatment. The MIC of LBM415 against M. pneumoniae was <0.005 μg/ml. LBM415-treated mice had significantly lower bronchoalveolar lavage fluid M. pneumoniae concentrations than placebo-treated mice on days 6 and 13 of treatment. Compared with placebo treatment, therapy with LBM415 significantly decreased lung histopathology scores at days 3, 6, and 13 of treatment and at 7 days after treatment. Airway obstruction was significantly lower in LBM415-treated mice than in placebo-treated mice on days 1, 3, and 6 of treatment and after 7 days of therapy, while airway hyperresponsiveness was significantly lower only on day 3 of therapy. The bronchoalveolar lavage fluid concentrations of tumor necrosis factor alpha, gamma interferon (IFN-γ), interleukin-6 (IL-6), IL-12, KC (functional IL-8), monocyte chemotactic protein 1, macrophage inflammatory protein 1α, monokine induced by IFN-γ, and IFN-inducible protein 10 were significantly reduced in LBM415-treated mice compared with the levels in placebo-treated mice. There were no differences in the bronchoalveolar lavage fluid concentrations of granulocyte-macrophage colony-stimulating factor, IL-1β, IL-2, IL-4, IL-5, and IL-10 between the two groups of mice. LBM415 therapy had beneficial microbiologic, histologic, respiratory, and immunologic effects on acute murine M. pneumoniae pneumonia.