Lung development and immune status under chronic LPS exposure in rat pups with and without CD26/DPP4 deficiency.

Dipeptidyl-peptidase IV (CD26), a multifactorial integral type II protein, is expressed in the lungs during development and is involved in inflammation processes. We tested whether daily LPS administration influences the CD26-dependent retardation in morphological lung development and induces alterations in the immune status. Newborn Fischer rats with and without CD26 deficiency were nebulized with 1 µg LPS/2 ml NaCl for 10 min from days postpartum (dpp) 3 to 9. We used stereological methods and fluorescence activated cell sorting (FACS) to determine morphological lung maturation and alterations in the pulmonary leukocyte content on dpp 7, 10, and 14. Daily LPS application did not change the lung volume but resulted in a significant retardation of alveolarization in both substrains proved by significantly lower values of septal surface and volume as well as higher mean free distances in airspaces. Looking at the immune status after LPS exposure compared to controls, a significantly higher percentage of B lymphocytes and decrease of CD4+CD25+ T cells were found in both subtypes, on dpp7 a significantly higher percentage of CD4 T+ cells in CD26+ pups, and a significantly higher percentage of monocytes in CD26- pups. The percentage of T cells was significantly higher in the CD26-deficient group on each dpp. Thus, daily postnatal exposition to low doses of LPS for 1 week resulted in a delay in formation of secondary septa, which remained up to dpp 14 in CD26- pups. The retardation was accompanied by moderate parenchymal inflammation and CD26-dependent changes in the pulmonary immune cell composition.

Postnatal morphological lung development of wild type and CD26/DPP4 deficient rat pups in dependency of LPS exposure.

BACKGROUND: Rodents are born with morphological immature lungs and an intact surfactant system. CD26/DPP4 is a multifactorial transmembrane integral type II protein, which is involved in physiological and pathophysiological processes and is already expressed during development. CD26/DPP4, called CD26 in the following, is able to enhance or dampen differently triggered inflammation. LPS exposure often used to simulate perinatal infection delays lung development. OBJECTIVE: A perinatal LPS rat model was used to test the hypothesis that CD26 deficiency modulates LPS-induced retardation in morphological lung development. METHODS: New born Fischer CD26 positive (CD26+) and deficient (CD26-) rats were exposed to LPS on postnatal day (day post partum, dpp) 3 and 5. Morphological parameters of lung development were determined stereologically. Lung development was analysed in 7, 10 14 and 21day old rats. RESULTS: Compared to controls LPS application resulted (1) in a mild inflammation independent of the strain, (2) in significantly lower total surface and volume of alveolar septa combined with significantly higher total volume of airspaces and alveolar size on dpp 7 in both substrains. However, compared to controls in LPS treated CD26- rats significant lower values of total septal surface and volume combined with higher values of total parenchymal airspaces and alveolar size were found until the end of classical alveolarization (dpp14). In LPS treated CD26+ rat pups the retardation was abolished already on dpp 10. CONCLUSION: In absence of CD26, LPS enhances the delay of morphological lung development. Morphological recovery was slower after the end of LPS exposure in CD26 deficient lungs.

Topical Nasal Anesthesia in Flexible Bronchoscopy--A Cross-Over Comparison between Two Devices.

INTRODUCTION: Topical airway anesthesia is known to improve tolerance and patient satisfaction during flexible bronchoscopy (FB). Lidocaine is commonly used, delivered as an atomized spray. The current study assesses safety and patient satisfaction for nasal anesthesia of a new atomization device during outpatient bronchoscopy in lung transplant recipients. METHODS: Using a prospective, non-blinded, cross-over design, patients enrolled between 01-10-2014 and 24-11-2014 received 2% lidocaine using the standard reusable nasal atomizer (CRNA). Those enrolled between 25-11-2014 and 30-01-2015, received a disposable intranasal mucosal atomization device (DIMAD). After each procedure, the treating physician, their assistant and the patient independently rated side-effects and satisfaction, basing their responses on visual analogue scales (VAS). At their next scheduled bronchoscopy during the study period, patients then received the alternative atomizer. Written consent was obtained prior to the first bronchoscopy, and the study approved by the institutional ethics committee. RESULTS: Of the 252 patients enrolled between 01-10-2014 and 30-01-2015, 80 (32%) received both atomizers. Physicians reported better efficacy (p = 0.001) and fewer side effects (p< = 0.001) for DIMAD in patients exposed to both procedures. Among patients with one visit, physicians and their assistants reported improved efficacy (p = 0.018, p = 0.002) and fewer side effects (p< = 0.001, p = 0.029) for the disposable atomizer, whereas patients reported no difference in efficacy or side effects (p = 0.72 and p = 0.20). No severe adverse events were noted. The cost of the reusable device was 4.08€ per procedure, compared to 3.70€ for the disposable device. DISCUSSION: Topical nasal anesthesia via a disposable intranasal mucosal atomization device (DIMAD) offers comparable safety and patient comfort, compared to conventional reusable nasal atomizers (CRNA) in lung transplant recipients. Procedural costs were reduced by 0.34€ per procedure. TRIAL REGISTRATION: clinicaltrials.gov NCT02237651.