Mucosal exposure to cockroach extract induces allergic sensitization and allergic airway inflammation

<p>Abstract</p> <p>Background</p> <p>Allergic sensitization to aeroallergens develops in response to mucosal exposure to these allergens. Allergic sensitization may lead to the development of asthma, which is characterized by chronic airway inflammation. The objective of this study is to describe in detail a model of mucosal exposure to cockroach allergens in the absence of an exogenous adjuvant.</p> <p>Methods</p> <p>Cockroach extract (CE) was administered to mice intranasally (i.n.) daily for 5 days, and 5 days later mice were challenged with CE for 4 consecutive days. A second group received CE i.n. for 3 weeks. Airway hyperresponsiveness (AHR) was assessed 24 h after the last allergen exposure. Allergic airway inflammation was assessed by BAL and lung histology 48 h after the last allergen exposure. Antigen-specific antibodies were assessed in serum. Lungs were excised from mice from measurement of cytokines and chemokines in whole lung lysate.</p> <p>Results</p> <p>Mucosal exposure of Balb/c mice to cockroach extract induced airway eosinophilic inflammation, AHR and cockroach-specific IgG1; however, AHR to methacholine was absent in the long term group. Lung histology showed patchy, multicentric damage with inflammatory infiltrates at the airways in both groups. Lungs from mice from the short term group showed increased IL-4, CCL11, CXCL1 and CCL2 protein levels. IL4 and CXCL1 were also increased in the BAL of cockroach-sensitized mice in the short-term protocol.</p> <p>Conclusions</p> <p>Mucosal exposure to cockroach extract in the absence of adjuvant induces allergic airway sensitization characterized by AHR, the presence of Th2 cytokines in the lung and eosinophils in the airways.</p

Extracorporeal Lung Support as a Bridge to Diagnosis of Pulmonary Tumor Embolism

Bridging to diagnosis is an emerging technique used in end-stage cardiorespiratory failure that prolongs a patient’s life using various modalities of extracorporeal lung support (ECLS) to achieve antemortem diagnosis. Pulmonary tumor embolism occurs when cell clusters travel from primary malignancies through venous circulation to the lungs, causing respiratory failure through inflammatory and venoocclusive pathways. Due to its nonspecific symptomatology, pulmonary tumor embolism remains an elusive diagnosis antemortem. Herein, we bridge a patient who presented in acute respiratory failure to the diagnosis of pulmonary tumor embolism from a gastric signet-ring cell carcinoma using ECLS modalities including venoarterial extracorporeal membrane oxygenation and centrally cannulated Novalung pumpless extracorporeal lung assist. We demonstrate the utility of this approach in diagnostically uncertain cases in unstable patients who are potentially acceptable ECLS and transplant candidates

Pulmonary Ossification Syndrome in a Patient with Chronic Thromboembolic Pulmonary Hypertension

First described more than 150 years ago, diffuse pulmonary ossification is a rare disease that can be idiopathic or secondary to an underlying chronic disorder. Commonly under-recognized and challenging to diagnose, clinical, radiographic and functional tests are often necessary. Given the increasing prevalence of chronic lung disease in the aging population, it is likely the pulmonary ossification will be encountered in clinics more often. This article describes the diagnosis of the condition in a 51-year-old man

The efficacy of tiotropium as a steroid-sparing agent in severe asthma

People with severe asthma account for 5% to 10% of all asthmatic patients; however, this small group uses the majority of health care resources. Novel methods are needed to cope with the burden that this minority of patients places on the health care system. A severe asthma clinic patient, who was monitored through the University of Alberta’s Virtual Asthma Clinic (Edmonton, Alberta) is presented. Despite optimization of his disease and individualized asthma education (provided by a certified asthma educator), the patient remained on oral glucocorticosteroids (OGS) to control his disease. Following optimization and stabilization, a further reduction in the dose of his OGS by the addition of the long-acting anticholinergic agent tiotropium bromide, was demonstrated. The role of tiotropium as a potential ‘steroid-sparing agent’ in severe refractory asthma is discussed, noting that if patients who are on OGS are not monitored for active inflammation, they may overuse the amount of prescribed systemic steroids, which can result in long-term steroid-related sequelae

EGFR as a biomarker of smoking status and survival in oropharyngeal squamous cell carcinoma

Abstract Background This study aims to investigate EGFR as a prognostic biomarker in oropharyngeal squamous cell carcinoma (OPSCC). Methods OPSCC patients from retrospective (1998–2009) and prospective cohorts (2014–2017) were included. Retrospectively collected tumors were used to construct tissue microarrays (TMAs), which were stained with EGFR, p16, DAPI and Pan-cytokeratin, and digitally quantified. EGFR, CDKN2A and HPV E6/7 levels from prospectively collected OPSCC was measured by droplet digital PCR (ddPCR). Biomarkers were compared to patient covariates, factors and survival outcomes. Results A total of 249 patients were included retrospectively and 64 patients were enrolled prospectively. p16 status (p < 0.001), smoking above 10 pack years (p = 0.04), smoking above 20 pack years (p < 0.001), total EGFR tumor levels (p = 0.016), and high EGFR within high or low Ki67 tumor nuclear staining (p = 0.03) were found to be significant predictors of 5-year disease specific survival (DSS). A Cox proportional hazard model of DSS showed smoking status and eGFR expression to be dependent of each other on predicting 5-year DSS. ddPCR analysis showed a significant association between smoking status and EGFR levels. Conclusions Total EGFR tumor levels are predictive of 5-year DSS. EGFR levels correlate with. smoking and could be an objective marker for this disease etiology