Female Sex and Gender in Lung/Sleep Health and Disease. Increased Understanding of Basic Biological, Pathophysiological, and Behavioral Mechanisms Leading to Better Health for Female Patients with Lung Disease

Female sex/gender is an undercharacterized variable in studies related to lung development and disease. Notwithstanding, many aspects of lung and sleep biology and pathobiology are impacted by female sex and female reproductive transitions. These may manifest as differential gene expression or peculiar organ development. Some conditions are more prevalent in women, such as asthma and insomnia, or, in the case of lymphangioleiomyomatosis, are seen almost exclusively in women. In other diseases, presentation differs, such as the higher frequency of exacerbations experienced by women with chronic obstructive pulmonary disease or greater cardiac morbidity among women with sleep-disordered breathing. Recent advances in -omics and behavioral science provide an opportunity to specifically address sex-based differences and explore research needs and opportunities that will elucidate biochemical pathways, thus enabling more targeted/personalized therapies. To explore the status of and opportunities for research in this area, the NHLBI, in partnership with the NIH Office of Research on Women's Health and the Office of Rare Diseases Research, convened a workshop of investigators in Bethesda, Maryland on September 18 and 19, 2017. At the workshop, the participants reviewed the current understanding of the biological, behavioral, and clinical implications of female sex and gender on lung and sleep health and disease, and formulated recommendations that address research gaps, with a view to achieving better health outcomes through more precise management of female patients with nonneoplastic lung disease. This report summarizes those discussions

Non-typeable Haemophilus Influenzae detection in the lower airways of patients with lung cancer and chronic obstructive pulmonary disease

Background: Chronic airway inflammation and hypersensitivity to bacterial infection may contribute to lung cancer pathogenesis. Previous studies have demonstrated that nontypeable Haemophilus influenzae (NTHi) is the most common colonizing bacteria in the lower airways of patients with COPD. The objective of this study was to determine the presence of NTHi and immunoglobulin concentrations in patients with lung cancer, COPD and controls. Methods: Serum and bronchial wash samples were collected from patients undergoing diagnostic bronchoscopy. Total IgE, IgG and specific NTHi IgG were measured by enzyme linked immunosorbent assay. Bronchial wash samples were examined for the presence of NTHi via PCR. Results: Out of the 60 patients: 20 had confirmed Lung Cancer, 27 had COPD only and 13 were used as Controls. NTHi was detected in the lower airways of all three groups (Lung Cancer 20%; COPD 22% and Controls 15%). Total IgE was highest in Lung Cancer subjects followed by COPD and control subjects (mean ± SD: 870 ± 944, 381 ± 442, 159 ± 115). Likewise total IgG was higher in Lung cancer (Mean ± SD: 6.99 ± 1.8) patients compared to COPD (Mean ± SD: 5.43 ± 2). Conclusions: The lack of difference in NTHi and specific antibodies between the three groups makes it less likely that NTHi has an important pathogenetic role in subjects with Lung Cancer. However the detection of higher IgE antibody in Lung Cancer subjects identifies a possible mechanism for carcinogenesis in these subjects and warrants further study.Griffith Health, School of MedicineFull Tex

American thoracic society/national heart, lung, and blood institute asthma-chronic obstructive pulmonary disease overlap workshop report

Asthma and chronic obstructive pulmonary disease (COPD) are highly prevalent chronic obstructive lung diseases with an associated high burden of disease. Asthma, which is often allergic in origin, frequently begins in infancy or childhood with variable airflow obstruction and intermittent wheezing, cough, and dyspnea. Patients with COPD, in contrast, are usually current or former smokers who present after the age of 40 years with symptoms (often persistent) including dyspnea and a productive cough. On the basis of age and smoking history, it is often easy to distinguish between asthma andCOPD. However, some patients have features compatible with both diseases. Because clinical studies typically exclude these patients, their underlying disease mechanisms and appropriate treatment remain largely uncertain. To explore the status of and opportunities for research in this area, the NHLBI, in partnership with the American Thoracic Society, convened a workshop of investigators in San Francisco, California on May 14, 2016. At the workshop, current understanding of asthma-COPD overlap was discussed among clinicians, pathologists, radiologists, epidemiologists, and investigators with expertise in asthma and COPD. They considered knowledge gaps in our understanding of asthma-COPD overlap and identified strategies and research priorities that will advance its understanding. This report summarizes those discussions

Lipid Motif of a Bacterial Antigen Mediates Immune Responses via TLR2 Signaling

The cross-talk between the innate and the adaptive immune system is facilitated by the initial interaction of antigen with dendritic cells. As DCs express a large array of TLRs, evidence has accumulated that engagement of these molecules contributes to the activation of adaptive immunity. We have evaluated the immunostimulatory role of the highly-conserved outer membrane lipoprotein P6 from non-typeable Haemophilus influenzae (NTHI) to determine whether the presence of the lipid motif plays a critical role on its immunogenicity. We undertook a systematic analysis of the role that the lipid motif plays in the activation of DCs and the subsequent stimulation of antigen-specific T and B cells. To facilitate our studies, recombinant P6 protein that lacked the lipid motif was generated. Mice immunized with non-lipidated rP6 were unable to elicit high titers of anti-P6 Ig. Expression of the lipid motif on P6 was also required for proliferation and cytokine secretion by antigen-specific T cells. Upregulation of T cell costimulatory molecules was abrogated in DCs exposed to non-lipidated rP6 and in TLR2−/− DCs exposed to native P6, thereby resulting in diminished adaptive immune responses. Absence of either the lipid motif on the antigen or TLR2 expression resulted in diminished cytokine production from stimulated DCs. Collectively; our data suggest that the lipid motif of the lipoprotein antigen is essential for triggering TLR2 signaling and effective stimulation of APCs. Our studies establish the pivotal role of a bacterial lipid motif on activating both innate and adaptive immune responses to an otherwise poorly immunogenic protein antigen

Importance of lysosomal cysteine proteases in lung disease

The human lysosomal cysteine proteases are a family of 11 proteases whose members include cathepsins B, C, H, L, and S. The biology of these proteases was largely ignored for decades because of their lysosomal location and the belief that their function was limited to the terminal degradation of proteins. In the past 10 years, this view has changed as these proteases have been found to have specific functions within cells. This review highlights some of these functions, specifically their roles in matrix remodeling and in regulating the immune response, and their relationship to lung diseases

Multicolor analysis of bone marrow stromal cells from normal and leukemic patients

Immunophenotypic analysis of bone marrow stromal cells selected by immunomagnetic technique in acute myeloid leukemi

Serratus anterior plane block for hybrid transthoracic esophagectomy: a pilot study

Cinzia Barbera,1 Pamela Milito,2 Michele Punturieri,1 Emanuele Asti,2 Luigi Bonavina2 1Anesthesiology Unit, 2Department of General Surgery, IRCCS Policlinico San Donato, University of Milan Medical School, Milano, Italy Background: Pain is a major limiting factor in patient’s recovery from major thoracic surgical procedures. Thoracic epidural analgesia (TEA), the current gold standard of perioperative management, has contraindications, can technically fail, and carries a risk of complications such as epidural abscess and spinal hematoma. The ultrasound-guided serratus anterior plane (SAP) block is a promising regional analgesia technique.Objectives: Since the anatomic space involved in the SAP block corresponds to the area exposed by the surgeon during right posterolateral thoracotomy, we investigated the feasibility of a “surgically guided” continuous SAP block as an alternative to TEA in selected esophagectomy patients.Study design: This was a pilot case-series study.Setting: This study was carried out in a tertiary-care university hospital.Methods: The demographic and clinical data of patients in whom the continuous SAP block was performed were retrieved from a prospectively maintained database of hybrid (laparoscopy plus right thoracotomy) Ivor Lewis esophagectomy. The SAP block was performed upon closure of the thoracotomy incision using a 19-gauge catheter tunnelized subcutaneously and positioned in the deep plane between the serratus anterior muscle and the ribs. A bolus dose of 30 mL of levobupivacaine 0.25% was injected, followed by a continuous infusion of the 0.125% solution at 7 mL/h until postoperative day 4.Results: Between January 2016 and July 2016, seven (20%) out of 37 esophagectomy patients underwent a SAP block rather than TEA for the following reasons: inability to insert the epidural catheter, antiaggregation or anticoagulant therapy, or unplanned thoracotomy. The procedure was uneventful in all patients. Only two patients required rescue analgesia on day 1.Conclusion: Continuous SAP block under direct vision is feasible and safe. This novel “surgically guided” application of the SAP block may be useful in case of failure or contraindications to TEA. Keywords: serratus anterior block, thoracic epidural anesthesia, post-thoracotomy pain, esophageal carcinoma, transthoracic esophagectom

Neoangiogenesis and its significance in MDS

Neoangiogenesis and its significance in MD

Multiparametric four color flow cytometric analysis of human bone marrow derived mesenchymal cells from normal and hematological patients.

Multiparametric four color flow cytometric analysis of human bone marrow derived mesenchymal cells from normal and hematological patient

Bone marrow stromal cells in acute promyelocytic leukaemia: comparison with other acute myelogenous leukaemia subtypes.

Bone marrow stromal cells in acute promyelocytic leukaemia: comparison with other acute myelogenous leukaemia subtypes