Rhinolalia as a presenting sign of pneumomediastinum complicating post peripheral blood stem cell transplantation bronchiolitis obliterans

A 26-year-old male with graft vs. host disease (GVHD) presented with rhinolalia (a squeaky voice of nasal quality) as a presenting sign for pneumonasopharynx and pneumomediastinum secondary to bronchiolitis obliterans. The patient underwent HLA-identical related peripheral blood stem cells transplantation 8 months before the diagnosis. Three weeks after transplantation he began to suffer from GVHD Grade III that involved the gut, liver, and skin and later on the lungs. Due to severe obstructive bronchiolitis obliterans the patient developed intensive cough evolving into pneumomediastinum and pneumonasopharynx with rhinolalia. The patient was treated conservatively with complete resolution. Although rare, pneumomediastinum and pneumonasopharynx can be a life-threatening event, and one should be aware of the signs and symptoms on physical examination, which may be as subtle as rhinolalia alone.     

CD4 T Cells but Not Th17 Cells Are Required for Mouse Lung Transplant Obliterative Bronchiolitis

Lung transplant survival is limited by obliterative bronchiolitis (OB), but the mechanisms of OB development are unknown. Previous studies in a mouse model of orthotopic lung transplantation suggested a requirement for IL‐17. We have used this orthotopic mouse model to investigate the source of IL‐17A and the requirement for T cells producing IL‐17A. The major sources of IL‐17A were CD4⁺ T cells and γδ T cells. Depletion of CD4⁺ T cells led to a significantly decreased frequency and number of IL‐17A⁺ lymphocytes and was sufficient to prevent acute rejection and OB. However, mice with STAT3‐deficient T cells, which are unable to differentiate into Th17 cells, rejected lung allografts and developed OB similar to control mice. The frequency of IL‐17A⁺ cells was not decreased in mice with STAT3‐deficient T cells due mainly to the presence of IL‐17A⁺ γδ T cells. Deficiency of γδ T cells also did not affect the development of airway fibrosis. Our data suggest that CD4⁺ T cells are required for OB development and expansion of IL‐17A responses in the lung, while Th17 and γδ T cells are not absolutely required and may compensate for each other.     

Changes in lung mechanics and histamine responsiveness after sequential canine adenovirus 2 and canine parainfluenza 2 virus infection in beagle puppies.

We determined the effects of an immediately antecedent viral lower respiratory tract infection (LRI) on the severity of clinical illness, changes in lung function and airway histamine responsiveness produced by a subsequent LRI in 9-12 week old beagle puppies inoculated with canine adenovirus 2, followed in 2 weeks by inoculation with canine parainfluenza 2 virus (CAV2-CP12, n = 7). We compared their acute responses to puppies infected with CP12 alone (n = 5), CAV2 alone (n = 7), and no infection (control, n = 6). Puppies inoculated with either virus alone developed a LRI 3 to 6 days after inoculation which resolved by 12-14 days after inoculation. However, the illness was more severe in the CAV2 group. In the CAV2-CP12 group, CP12 infection following CAV2 infection resulted in a clinical illness nearly comparable to that observed with CAV2 alone. Whereas in control and CP12 puppies, lung resistance (RL) decreased and dynamic lung compliance (Cdyn) increased during the study due to normal growth, RL increased and Cdyn remained unchanged in the CAV2 group. In contrast, RL did not change and Cdyn increased in the CAV2-CP12 group. Airway histamine responsiveness in the CAV2-CP12 group increased during infection with CP12 and was similar to that observed with CAV2 alone. In contrast, infection with CP12 alone produced a small, but non-significant increase in histamine responsiveness. The duration of the increase in histamine responsiveness was not prolonged in the CAV2-CP12 group in comparison to CP12 or CAV2 alone. However, the length of clinical illness was extended in the CAV2-CP12 group in comparison to the other infected groups. These data suggest that an immediately antecedent viral LRI can potentiate the clinical and physiologic effects of a subsequent viral LRI.     

The functional response of infants with persistent wheezing to nebulized beclomethasone dipropionate

Lung function was measured in nine infants, ages 15-36 weeks, who had persistent wheezing, apparently following acute bronchiolitis, before and after 2 weeks of treatment with either inhaled nebulized beclomethasone dipropionate (BDP) or placebo in a randomized, double blind, crossover trial. The effect of nebulized albuterol (Salbutamol) was measured before and after the steroid treatment. Thoracic gas volume (TGV) and specific airway conductance (SGaw) were determined using a whole body plethysmograph, and forced expiratory flow at resting lung volume (VmaxFRC) was determined with a thoracoabdominal compression jacket. All infants had marked airways obstruction before treatment with mean +/- SE VmaxFRC of 24 +/- 4% predicted and SGaw of 37 +/- 5% predicted. Two weeks of placebo treatment had no significant effect on lung function, but after 2 weeks of BDP inhalation there was a significant rise in SGaw to 61 +/- 7% (P less than 0.005). VmaxFRC increased to 42 +/- 13% but the difference did not reach significance. Respiratory rate and clinical score for retractions and wheezing also fell significantly with BDP therapy (P less than 0.01 and P less than 0.001 respectively). Albuterol had no effect on lung function either before or during steroid therapy. Steroids may have a role in the management of persistent wheezing following bronchiolitis.