The Immunopathologic Effects of Mycoplasma pneumoniae and Community-acquired Respiratory Distress Syndrome Toxin. A Primate Model.

Mycoplasma pneumoniae infection has been linked to poor asthma outcomes. M. pneumoniae produces an ADP-ribosylating and vacuolating toxin called community-acquired respiratory distress syndrome (CARDS) toxin that has a major role in inflammation and airway dysfunction. The objective was to evaluate the immunopathological effects in primates exposed to M. pneumoniae or CARDS toxin. A total of 13 baboons were exposed to M. pneumoniae or CARDS toxin. At Days 7 and 14, BAL fluid was collected and analyzed for cell count, percent of each type of cell, CARDS toxin by PCR, CARDS toxin by antigen capture, eosinophilic cationic protein, and cytokine profiles. Serum IgM, IgG, and IgE responses to CARDS toxin were measured. All animals had a necropsy for analysis of the histopathological changes on lungs. No animal developed signs of infection. The serological responses to CARDS toxin were variable. At Day 14, four of seven animals exposed to M. pneumoniae and all four animals exposed to CARDS toxin developed histological "asthma-like" changes. T cell intracellular cytokine analysis revealed an increasing ratio of IL-4/IFN-γ over time. Both M. pneumoniae and CARDS toxin exposure resulted in similar histopathological pulmonary changes, suggesting that CARDS toxin plays a major role in the inflammatory response.

THE EFFICACY OF AN EIGHT-WEEK CORE STABILIZATION PROGRAM ON CORE MUSCLE FUNCTION AND ENDURANCE: A RANDOMIZED TRIAL.

BACKGROUND: Body armor is credited with increased survival rates in soldiers but the additional axial load may negatively impact the biomechanics of the spine resulting in low back pain. Multiple studies have found that lumbar stabilization programs are superior to generalized programs for patients with chronic low back pain. It is not known if such programs produce objective changes in trunk muscle function with wear of body armor. HYPOTHESIS/PURPOSE: An eight-week core stability exercise program would result in a larger improvement in physical endurance and abdominal muscle thickness than a control intervention. The purpose of this study was to assess the effectiveness of an eight-week core stability exercise program on physical endurance and abdominal muscle thickness with and without wear of body armor. STUDY DESIGN: Randomized controlled trial. METHODS: Participants (N = 33) were randomized into either the core strengthening exercise group or the control group. Testing included ultrasound imaging of abdominal muscle thickness in hook-lying and standing with and without body armor and timed measures of endurance. RESULTS: There were statistically significant group by time interactions for transversus abdominis muscle contraction thickness during standing, both with (p = 0.018) and without body armor (p = 0.038). The main effect for hold-time during the horizontal side-support (p = 0.016) indicated improvement over time regardless of group. There was a significant group by time interaction (p = 0.014) for horizontal side-support hold-time when compliance with the exercise protocol was set at 85%, indicating more improvement in the core stabilization group than in the control group. CONCLUSION: Performing an eight-week core stabilization exercise program significantly improves transversus abdominis muscle activation in standing and standing with body armor. When compliant with the exercises, such a program may increase trunk strength and muscle endurance. LEVELS OF EVIDENCE: Therapy, Level 2b.

ULTRASOUND IMAGING MEASUREMENT OF THE TRANSVERSUS ABDOMINIS IN SUPINE, STANDING, AND UNDER LOADING: A RELIABILITY STUDY OF NOVICE EXAMINERS.

BACKGROUND: Military personnel and first responders (police and firefighters) often carry large amounts of gear. This increased load can negatively affect posture and lead to back pain. The ability to quantitatively measure muscle thickness under loading would be valuable to clinicians to assess the effectiveness of core stabilization treatment programs and could aid in return to work decisions. Ultrasound imaging (USI) has the potential to provide such a measure, but to be useful it must be reliable. PURPOSE: To assess the intrarater and interrater reliability of measurements of transversus abdominis (TrA) and internal oblique (IO) muscle thickness conducted by novice examiners using USI in supine, standing, and with an axial load. STUDY DESIGN: Prospective, test-retest study. METHODS: Healthy, active duty military (N=33) personnel were examined by two physical therapy doctoral students (primary and secondary ultrasound technicians) without prior experience in USI. Thickness measurements of the TrA and IO muscles were performed at rest and during a contraction to preferentially activate the TrA in three positions (hook-lying, standing, and standing with body armor). Percent thickness changes and intraclass correlation coefficients (ICC) were calculated. RESULTS: Using the mean of three measurements for each of the three positions in resting and contracted muscle states, the intrarater ICC (3,3) values ranged from 0.90 to 0.98. The interrater ICC (2,1) values ranged from 0.39 to 0.79. The ICC values of percent thickness changes were lower than the individual ICC values for all positions and muscle states. CONCLUSION: There is excellent intrarater reliability of novice ultrasound technicians measuring abdominal muscle thickness using USI in three positions during the resting and contracted muscle states. However, interrater reliability of two novice technicians was poor to fair, so additional training and experience may be necessary to improve reliability. LEVEL OF EVIDENCE: 2b.

Mycoplasma pneumoniae CARDS toxin exacerbates ovalbumin-induced asthma-like inflammation in BALB/c mice.

Mycoplasma pneumoniae causes a range of airway and extrapulmonary pathologies in humans. Clinically, M. pneumoniae is associated with acute exacerbations of human asthma and a worsening of experimentally induced asthma in mice. Recently, we demonstrated that Community Acquired Respiratory Distress Syndrome (CARDS) toxin, an ADP-ribosylating and vacuolating toxin synthesized by M. pneumoniae, is sufficient to induce an asthma-like disease in BALB/cJ mice. To test the potential of CARDS toxin to exacerbate preexisting asthma, we examined inflammatory responses to recombinant CARDS toxin in an ovalbumin (OVA) murine model of asthma. Differences in pulmonary inflammatory responses between treatment groups were analyzed by histology, cell differentials and changes in cytokine and chemokine concentrations. Additionally, assessments of airway hyperreactivity were evaluated through direct pulmonary function measurements. Analysis of histology revealed exaggerated cellular inflammation with a strong eosinophilic component in the CARDS toxin-treated group. Heightened T-helper type-2 inflammatory responses were evidenced by increased expression of IL-4, IL-13, CCL17 and CCL22 corresponding with increased airway hyperreactivity in the CARDS toxin-treated mice. These data demonstrate that CARDS toxin can be a causal factor in the worsening of experimental allergic asthma, highlighting the potential importance of CARDS toxin in the etiology and exacerbation of human asthma.

Mycoplasma pneumoniae in children with acute and refractory asthma.

BACKGROUND: The presence of Mycoplasma pneumoniae has been associated with worsening asthma in children. Sensitive assays have been developed to detect M pneumoniae-derived community-acquired respiratory distress syndrome (CARDS) toxin. OBJECTIVES: To identify the frequency and persistence of M pneumoniae detection in respiratory secretions of children with and without asthma and to evaluate antibody responses to M pneumoniae and the impact of M pneumoniae on biological markers, asthma control, and quality of life. METHODS: We enrolled 143 pediatric patients (53 patients with acute asthma, 26 patients with refractory asthma, and 64 healthy controls; age range, 5-17 years) during a 20-month period with 2 to 5 follow-up visits. We detected M pneumoniae using CARDS toxin antigen capture and polymerase chain reaction and P1 adhesin polymerase chain reaction. Immune responses to M pneumoniae were determined by IgG and IgM levels directed against CARDS toxin and P1 adhesin. pH was measured in exhaled breath condensates, and asthma control and quality of life were assessed using the Asthma Control Test and Pediatric Asthma Quality of Life Questionnaire. RESULTS: M pneumoniae was detected in 64% of patients with acute asthma, 65% with refractory asthma, and 56% of healthy controls. Children with asthma had lower antibody levels to M pneumoniae compared with healthy controls. Exhaled breath condensate pHs and asthma control and quality of life scores were lower in M pneumoniae-positive patients with asthma. CONCLUSION: The results suggest that M pneumoniae detection is common in children, M pneumoniae detection is associated with worsening asthma, and children with asthma may have poor humoral immune responses to M pneumoniae.

Mycoplasma pneumoniae CARDS toxin induces pulmonary eosinophilic and lymphocytic inflammation.

Mycoplasma pneumoniae causes acute and chronic lung infections in humans, leading to a variety of pulmonary and extrapulmonary sequelae. Of the airway complications of M. pneumoniae infection, M. pneumoniae-associated exacerbation of asthma and pediatric wheezing are emerging as significant sources of human morbidity. However, M. pneumoniae products capable of promoting allergic inflammation are unknown. Recently, we reported that M. pneumoniae produces an ADP-ribosylating and vacuolating toxin termed the community-acquired respiratory distress syndrome (CARDS) toxin. Here we report that naive mice exposed to a single dose of recombinant CARDS (rCARDS) toxin respond with a robust inflammatory response consistent with allergic disease. rCARDS toxin induced 30-fold increased expression of the Th-2 cytokines IL-4 and IL-13 and 70- to 80-fold increased expression of the Th-2 chemokines CCL17 and CCL22, corresponding to a mixed cellular inflammatory response comprised of a robust eosinophilia, accumulation of T cells and B cells, and mucus metaplasia. The inflammatory responses correlate temporally with toxin-dependent increases in airway hyperreactivity characterized by increases in airway restriction and decreases in lung compliance. Furthermore, CARDS toxin-mediated changes in lung function and histopathology are dependent on CD4(+) T cells. Altogether, the data suggest that rCARDS toxin is capable of inducing allergic-type inflammation in naive animals and may represent a causal factor in M. pneumoniae-associated asthma.