Abnormal alveolar wound repair contributes to the development of pulmonary fibrosis after lung injury. Hepatocyte growth factor (HGF) is a potent mitogenic factor for alveolar epithelial cells and may therefore improve alveolar epithelial repair in vitro and in vivo. We hypothesized that HGF could increase alveolar epithelial repair in vitro and improve pulmonary fibrosis in vivo. Alveolar wound repair in vitro was determined using an epithelial wound repair model with HGF-transfected A549 alveolar epithelial cells. Electroporation-mediated, nonviral gene transfer of HGF in vivo was performed 7 days after bleomycin-induced lung injury in the rat. Alveolar epithelial repair in vitro was increased after transfection of wounded epithelial monolayers with a plasmid encoding human HGF, pCikhHGF [human HGF (hHGF) gene expressed from the cytomegalovirus (CMV) immediate-early promoter and enhancer] compared with medium control. Electroporation-mediated in vivo HGF gene transfer using pCikhHGF 7 days after intratracheal bleomycin reduced pulmonary fibrosis as assessed by histology and hydroxyproline determination 14 days after bleomycin compared with controls treated with the same vector not containing the HGF sequence (pCik). Lung epithelial cell proliferation was increased and apoptosis reduced in hHGF-treated lungs compared with controls, suggesting increased alveolar epithelial repair in vivo. In addition, profibrotic transforming growth factor-beta1 (TGF-beta1) was decreased in hHGF-treated lungs, indicating an involvement of TGF-beta1 in hHGF-induced reduction of lung fibrosis. In conclusion, electroporation-mediated gene transfer of hHGF decreases bleomycin-induced pulmonary fibrosis, possibly by increasing alveolar epithelial cell proliferation and reducing apoptosis, resulting in improved alveolar wound repair.

BackgroundPulmonary tularaemia is a very rare disease with only a small number of cases described in the literature. So far, to our knowledge, there exists no case report of pulmonary tularaemia where PET-CT scans and follow up CT scans are available.Case presentationWe present four consecutive cases of pulmonary tularaemia. All patients suffered from non-specific symptoms. All patients were referred to our institution with strong suspicions of malignancy, particularly lung cancer.Diagnosis of tularaemia was made by typical findings in the aspirate of EBUS guided fine needle aspiration (necrosis, epithelioid cell aggregation) and surgical biopsy respectively, and a positive serology. In three of the four cases, the diagnosis was confirmed by positive PCR results of the tissue. PET-CT scans obtained in all four cases were indistinguishable from lesions typically seen in patients suffering from lung cancer.One of the four patients suffered from recurrence of the disease after antibiotic treatment; also this patient finally recovered after initiation of a second antibiotic regimen. One case became asymptomatic spontaneously, but this patient still received an antibiotic treatment.In one case, a follow up CT scan was unchanged compared to the initial PET-CT scan; in all other cases, the lesions disappeared almost completely.ConclusionsSymptoms of patients suffering from pulmonary tularaemia are non-specific and can be of prolonged character. PET-CT scans in these cases are indistinguishable from lung cancer. The diagnosis can be established when typical findings in EBUS guided fine needle aspirates or surgical biopsies are found in combination with a positive serology. In most cases the lesions disappear in follow up CT scans after clinically successful treatment.

Expression of NK-2R and PPT-A is increased in CP and is associated with pain. Failure to up-regulate NEP may contribute to the disruption of the neuropeptides loop balance in CP and thus may exacerbate the severe pain syndrome.

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ObjectivesThe olfactory function highly impacts quality of life (QoL). Continuous positive airway pressure is an effective treatment for obstructive sleep apnea (OSA) and is often applied by nasal masks (nCPAP). The influence of nCPAP on the olfactory performance of OSA patients is unknown. The aim of this study was to assess the sense of smell before initiation of nCPAP and after three months treatment, in moderate and severe OSA patients.MethodsThe sense of smell was assessed in 35 patients suffering from daytime sleepiness and moderate to severe OSA (apnea/hypopnea index ≥ 15/h), with the aid of a validated test battery (Sniffin’ Sticks) before initiation of nCPAP therapy and after three months of treatment. Additionally, adherent subjects were included in a double-blind randomized three weeks CPAP-withdrawal trial (sub-therapeutic CPAP pressure).ResultsTwenty five of the 35 patients used the nCPAP therapy for more than four hours per night, and for more than 70% of nights (adherent group). The olfactory performance of these patients improved significantly (p = 0.007) after three months of nCPAP therapy. When considering the entire group of patients, olfaction also improved significantly (p = 0.001). In the randomized phase the sense of smell of six patients deteriorated under sub-therapeutic CPAP pressure (p = 0.046) whereas five patients in the maintenance CPAP group showed no significant difference (p = 0.501).ConclusionsOlfactory performance improved significantly after three months of nCPAP therapy in patients suffering from moderate and severe OSA. It seems that this effect of nCPAP is reversible under sub-therapeutic CPAP pressure.Trial registrationISRCTN11128866