Nina Patel

Pulmonary arteriole gene expression signature in idiopathic pulmonary fibrosis

A third of patients with idiopathic pulmonary fibrosis (IPF) develop pulmonary hypertension (PH-IPF), which is associated with increased mortality. Whether an altered gene expression profile in the pulmonary vasculature precedes the clinical onset of PH-IPF is unknown. We compared gene expression in the pulmonary vasculature of IPF patients with and without PH with controls. Pulmonary arterioles were isolated using laser capture microdissection from 16 IPF patients: eight with PH (PH-IPF) and eight with no PH (NPH-IPF), and seven controls. Probe was prepared from extracted RNA, and hybridised to Affymetrix Hu133 2.0 Plus genechips. Biometric Research Branch array tools and Ingenuity Pathway Analysis software were used for analysis of the microarray data. Univariate analysis revealed 255 genes that distinguished IPF arterioles from controls (p<0.001). Mediators of vascular smooth muscle and endothelial cell proliferation, Wnt signalling and apoptosis were differentially expressed in IPF arterioles. Unsupervised and supervised clustering analyses revealed similar gene expression in PH-IPF and NPH-IPF arterioles. The pulmonary arteriolar gene expression profile is similar in IPF patients with and without coexistent PH. Pathways involved in vascular proliferation and aberrant apoptosis, which may contribute to pulmonary vascular remodelling, are activated in IPF patients.

Extracorporeal membrane oxygenation for refractory acute respiratory distress syndrome in severe malaria

BackgroundSevere malaria may be complicated by the acute respiratory distress syndrome (ARDS), which is associated with a high mortality. In the present report, a series of three cases of imported malaria complicated by refractory severe ARDS supported with extracorporeal membrane oxygenation (ECMO) is presented.MethodsOne female and two male adult patients (ages 39 to 53) were included. Two patients had Plasmodium falciparum infection and one patient had Plasmodium vivax and Plasmodium ovale co-infection. Anti-malarial therapy consisted in intravenous quinine (in two patients) and intravenous quinidine (in one patient), plus clindamycin or doxycycline.ResultsDespite lung protective ventilation, a conservative strategy of fluid management, corticosteroids (two patients), prone position (two patients) and inhaled nitric oxide (one patient), refractory severe ARDS supervened (PaO2 to FiO2 ratio 68) and venovenous ECMO was then initiated. In one patient, a bicaval dual-lumen cannula was inserted; in the two other patients, a two-site configuration was used. Two patients survived to hospital-discharge (duration of ECMO support: 8.5 days) and one patient died from nosocomial sepsis and multi-organ failure after 40 days of ECMO support.ConclusionsECMO support allowed adequate oxygenation and correction of hypercapnia under lung protective ventilation, therefore reducing ventilator-induced lung injury. ECMO referral should be considered early in malaria complicated by severe ARDS refractory to conventional treatment.

Cryobiopsy in the Diagnosis of Interstitial Lung Disease. A Step Forward or Back

high CTX and low-normal P1NP levels, are likely to reflect the rapid changes that were already occurring in these subjects as a result either of the effect of glucocorticoids or immobilization or of both. Although the reductions in BMD were significant, the average reduction was small and well within the least significant change of the measurement. This means that for a given patient, the small reduction in BMD at 1 year might not be statistically significant. To be confident of a statistically significant reduction in BMD at the 95% confidence level (10), the changes in an individual patient would have had to be 1.77% at the lumbar spine and 4.43% at the femoral neck (multiply the precision of the measurement, as reported by the authors, of 0.6% at the lumbar spine and 1.6% at the femoral neck by a factor of 2.77). As reported in the article, the standard deviation of these mean reductions is large, suggesting some would have experienced significant reductions in BMD during this period. It would have been interesting to know whether those with the greatest reductions were those who were treated with glucocorticoids. It is also important to point out that the reduction at the 1 year point may not reflect a true decline during that entire period. In this setting, particularly if the data are driven by immobilization and those who were treated with glucocorticoids, there might have been more rapid declines at the 3 month and 6 month points. The 1 year measurement might reflect partial recovery of more significant short-term reductions in BMD. This article is a successful exploration into the chronology and dynamics of bone loss in the ICU setting. We look forward to additional work to elucidate further the basis for these observations.n

Outcomes of immunosuppressive therapy in chronic hypersensitivity pneumonitis

In chronic hypersensitivity pneumonitis (CHP), lack of improvement or declining lung function may prompt use of immunosuppressive therapy. We hypothesised that use of azathioprine or mycophenolate mofetil with prednisone reduces adverse events and lung function decline, and improves transplant-free survival. Patients with CHP were identified. Demographic features, pulmonary function tests, incidence of treatment-emergent adverse events (TEAEs) and transplant-free survival were characterised, compared and analysed between patients stratified by immunosuppressive therapy. A multicentre comparison was performed across four independent tertiary medical centres. Among 131 CHP patients at the University of Chicago medical centre (Chicago, IL, USA), 93 (71%) received immunosuppressive therapy, and had worse baseline forced vital capacity (FVC) and diffusing capacity, and increased mortality compared with those who did not. Compared to patients treated with prednisone alone, TEAEs were 54% less frequent with azathioprine therapy (p=0.04) and 66% less frequent with mycophenolate mofetil (p=0.002). FVC decline and survival were similar between treatment groups. Analyses of datasets from four external tertiary medical centres confirmed these findings. CHP patients who did not receive immunosuppressive therapy had better survival than those who did. Use of mycophenolate mofetil or azathioprine was associated with a decreased incidence of TEAEs, and no difference in lung function decline or survival when compared with prednisone alone. Early transition to mycophenolate mofetil or azathioprine may be an appropriate therapeutic approach in CHP, but more studies are needed. Early transition to mycophenolate mofetil or azathioprine may be an appropriate therapeutic approach in CHP http://ow.ly/kAN130dRIX8