http://www.biomedcentral.com/bmcpulmmed/ The editor's pick of recent articles published by BMC Pulmonary Medicine 2012-03-29T00:00:00Z Background: Surfactant protein C (SP-C) is important for the function of pulmonary surfactant. Heterozygous mutations in SFTPC, the gene encoding SP-C, cause sporadic and familial interstitial lung disease (ILD) in children and adults. Mutations mapping to the BRICHOS domain located within the SP-C proprotein result in perinuclear aggregation of the proprotein. In this study, we investigated the effects of the mutation A116D in the BRICHOS domain of SP-C on cellular homeostasis. We also evaluated the ability of drugs currently used in ILD therapy to counteract these effects. Methods: SP-CA116D was expressed in MLE-12 alveolar epithelial cells. We assessed in vitro the consequences for cellular homeostasis, immune response and effects of azathioprine, hydroxychloroquine, methylprednisolone and cyclophosphamide. Results: Stable expression of SP-CA116D in MLE-12 alveolar epithelial cells resulted in increased intracellular accumulation of proSP-C processing intermediates. SP-CA116D expression further led to reduced cell viability and increased levels of the chaperones Hsp90, Hsp70, calreticulin and calnexin. Lipid analysis revealed decreased intracellular levels of phosphatidylcholine (PC) and increased lyso-PC levels. Treatment with methylprednisolone or hydroxychloroquine partially restored these lipid alterations. Furthermore, SP-CA116D cells secreted soluble factors into the medium that modulated surface expression of CCR2 or CXCR1 receptors on CD4+ lymphocytes and neutrophils, suggesting a direct paracrine effect of SP-CA116D on neighboring cells in the alveolar space. Conclusions: We show that the A116D mutation leads to impaired processing of proSP-C in alveolar epithelial cells, alters cell viability and lipid composition, and also activates cells of the immune system. In addition, we show that some of the effects of the mutation on cellular homeostasis can be antagonized by application of pharmaceuticals commonly applied in ILD therapy. Our findings shed new light on the pathomechanisms underlying SP-C deficiency associated ILD and provide insight into the mechanisms by which drugs currently used in ILD therapy act. http://www.biomedcentral.com/1471-2466/12/15 Ralf Zarbock Markus Woischnik Christiane Sparr Tobias Thurm Suncana Kern Eva Kaltenborn Andreas Hector Dominik Hartl Gerhard Liebisch Gerd Schmitz Matthias Griese BMC Pulmonary Medicine 2012, 12:15 2012-03-29T00:00:00Z 10.1186/1471-2466-12-15 Effects of SP-C mutation in vitro Mutations to the gene encoding Surfactant protein C (SP-C) are implicated in interstitial lung disease; the A116D mutation impairs processing of proSP-C in vitro, leading to altered cell viability, surfactant lipid composition and activation of immune cells. /content/figures/1471-2466-12-15-toc.gif BMC Pulmonary Medicine 1471-2466 12 15 2012-03-29T00:00:00Z PDF Background: The aim of this study was to assess the responsiveness of the asthma control test (ACT) to detect changes at the initiation of therapy and its utilization in the initiation of asthma treatment. Methods: This study was designed as a randomized clinical trial conducted in a primary care setting. The subjects were asthma patients who had not received controller therapy for at least two months. The patients were randomized into two groups: The Saudi Initiative for Asthma (SINA) group and the Global Initiative for Asthma (GINA) group. Treatment in the SINA group was initiated at step1 when the ACT scores ≥ 20, step 2 when the score between16-19, and step 3 when the score < 16 began at step 3. The GINA group patients were started on step 2 when they had persistent asthma symptoms or step 3 when they had severely uncontrolled disease. Results: Forty-five patients were analyzed in each group. The improvement in ACT score after treatment initiation was significantly higher when the SINA approach was used (2.9 in the SINA group compared to 1.7 in the GINA group (p = 0.04)). The improvement in FEV1 was 5.8% in the SINA group compared to 3.4% in the GINA group (p = 0.46). The number of patients who achieved asthma control at the follow-up visit and required no treatment adjustment was 33 (73.3%) in the SINA group and 27 (60%) in the GINA group (p = 0.0125). Conclusion: The ACT was responsive to change at the initiation of asthma treatment and was useful for the initiation of asthma treatment.Trial Registration numberISRCTN31998214 http://www.biomedcentral.com/1471-2466/12/14 Mohamed S Al Moamary Ahmed G Al-Kordi Mohammed O Al Ghobain Hani M Tamim BMC Pulmonary Medicine 2012, 12:14 2012-03-26T00:00:00Z 10.1186/1471-2466-12-14 Utilisation of the ACT in primary care In a primary care setting, the Asthma Control Test (ACT) is responsive to changes in lung function at the initiation of asthma treatment, and may be useful for the initiation of asthma treatment. /content/figures/1471-2466-12-14-toc.gif BMC Pulmonary Medicine 1471-2466 12 14 2012-03-26T00:00:00Z XML Background: The aim of our study was to investigate the predictive value of the biomarkers interleukin 6 (IL-6), interleukin 10 (IL-10) and lipopolysaccharide-binding protein (LBP) compared with clinical CRB and CRB-65 severity scores in patients with community-acquired pneumonia (CAP). Methods: Samples and data were obtained from patients enrolled into the German CAPNETZ study group. Samples (blood, sputum and urine) were collected within 24 h of first presentation and inclusion in the CAPNETZ study, and CRB and CRB-65 scores were determined for all patients at the time of enrollment. The combined end point representative of a severe course of CAP was defined as mechanical ventilation, intensive care unit treatment and/or death within 30 days. Overall, a total of 1,000 patients were enrolled in the study. A severe course of CAP was observed in 105 (10.5%) patients. Results: The highest IL-6, IL-10 and LBP concentrations were found in patients with CRB-65 scores of 3-4 or CRB scores of 2-3. IL-6 and LBP levels on enrollment in the study were significantly higher for patients with a severe course of CAP than for those who did not have severe CAP. In receiver operating characteristic analyses, the area under the curve values for of IL-6 (0.689), IL-10 (0.665) and LPB (0.624) in a severe course of CAP were lower than that of CRB-65 (0.764) and similar to that of CRB (0.69). The accuracy of both CRB and CRB-65 was increased significantly by including IL-6 measurements. In addition, higher cytokine concentrations were found in patients with typical bacterial infections compared with patients with atypical or viral infections and those with infection of unknown etiology. LBP showed the highest discriminatory power with respect to the etiology of infection. Conclusions: IL-6, IL-10 and LBP concentrations were increased in patients with a CRB-65 score of 3-4 and a severe course of CAP. The concentrations of IL-6 and IL-10 reflected the severity of disease in patients with CAP. The predictive power of IL-6, IL-10 and LBP for a severe course of pneumonia was lower than that of CRB-65. Typical bacterial pathogens induced the highest LBP, IL-6 and IL-10 concentrations. http://www.biomedcentral.com/1471-2466/12/6 Katrin Zobel Peter Martus Mathias W Pletz Santiago Ewig Michael Prediger Tobias Welte Frank Bühling CAPNETZ study group BMC Pulmonary Medicine 2012, 12:6 2012-02-20T00:00:00Z 10.1186/1471-2466-12-6 Biomarkers for CAP Patients with a severe course of community-aquired pneumonia (CAP) exhibit increased levels of interleukin 6, 10 and lipopolysaccharide-binding protein, however the predictive power of these factors for a severe course of pneumonia is lower than that of CRB-65. /content/figures/1471-2466-12-6-toc.gif BMC Pulmonary Medicine 1471-2466 12 6 2012-02-20T00:00:00Z XML