Related Articles

Therapeutic granulocyte and monocyte apheresis (GMA) for treatment refractory sarcoidosis: a pilot study of clinical effects and possible mechanisms of action.

Clin Exp Immunol. 2014 Sep;177(3):712-9

Authors: Olsen HH, Muratov V, Cederlund K, Lundahl J, Eklund A, Grunewald J

Abstract
Sarcoidosis is a systemic, inflammatory disorder, which in a proportion of patients runs a chronic progressive course despite immunosuppressive treatment. Therapeutic granulocyte and monocyte apheresis (GMA) has been shown to be an effective treatment option for other systemic inflammatory disorders, but has not yet been investigated in sarcoidosis. The aim of this study was to evaluate the response to GMA in sarcoidosis. Seven patients with sarcoidosis refractory to standard immunosuppressive therapy received 10 GMA sessions. All patients underwent chest X-ray, spirometry, a Chronic Respiratory Disease Questionnaire (CRQ-SAS), blood tests and bronchoscopy with bronchoalveolar lavage (BAL) before treatment and at 2-4 weeks and 3 months (except bronchoscopy) after the last treatment session. Bronchoalveolar lavage fluid (BALF) cell differential counts were recorded and T cells from blood and BALF were analysed for markers of activity, differentiation and T regulatory function. Compared to baseline, five of seven patients reported an improvement in dyspnoea score. In BALF there was an increase in the percentage of macrophages and a decrease in the percentage of lymphocytes and CD4(+) /FoxP3(+) T cells. Furthermore, the decrease in BALF CD4(+) /FoxP3(+) T cells correlated significantly with an improvement in dyspnoea score. In peripheral blood there was a statistically significant increase in the percentage of CD4(+) /CD27(-) T cells and a trend towards an initial increase in the percentage of CD4(+) /FoxP3(+) T cells, followed by a statistically significant decrease. The effects of GMA on regulatory T cells are consistent with those observed in other inflammatory disorders and could potentially translate into a clinical benefit.

PMID: 24773420 [PubMed - indexed for MEDLINE]

Lire la suite...

Related Articles

Incertainty exists about the benefit of oral anticoagulation in the treatment of pulmonary arterial hypertension (PAH), which is a lethal disease. We aimed to review and quantify the effect of oral anticoagulants in overall survival of PAH patients.

METHODS: We searched for randomized and observational studies that evaluated oral anticoagulants in PAH in the electronic databases MEDLINE, CENTRAL and ISI Web of Knowledge (December 2013). Review articles and references were also screened. We performed a random effects meta-analysis to estimate pooled HRs and 95% confidence intervals. Statistical heterogeneity was evaluated using the I(2) test.

RESULTS: No randomized controlled trials were identified. Nine cohort studies (2 prospective and 7 retrospective) of overall moderate quality that enrolled 1730 PAH patients were included. Oral anticoagulation (warfarin) was associated with a 31% mortality risk reduction (HR, 0.69; 95% confidence interval, 0.57-0.82; I(2) = 28%). Subgroup and sensitivity analyses showed similar results and no significant heterogeneity.

CONCLUSIONS: There is no randomized evidence to support the use of oral anticoagulation in PAH. Pooled results from cohort studies suggest a survival benefit, but the moderate study quality, the high risk of publication bias, and the methodological limitations inherent in the analysis of observational studies preclude a definite conclusion. There is an urgent need for pragmatic randomized evidence to definitely answer this important clinical question.

Lire la suite...

Related Articles

Adult-onset asthma and chronic obstructive pulmonary disease (COPD) are major public health burdens. This review presents a comprehensive synopsis of their epidemiology, pathophysiology, and clinical presentations; describes how they can be distinguished; and considers both established and proposed new approaches to their management. Both adult-onset asthma and COPD are complex diseases arising from gene-environment interactions.

Early life exposures such as childhood infections, smoke, obesity, and allergy influence adult-onset asthma. While the established environmental risk factors for COPD are adult tobacco and biomass smoke, there is emerging evidence that some childhood exposures such as maternal smoking and infections may cause COPD. Asthma has been characterized predominantly by Type 2 helper T cell (Th2) cytokine-mediated eosinophilic airway inflammation associated with airway hyperresponsiveness. In established COPD, the inflammatory cell infiltrate in small airways comprises predominantly neutrophils and cytotoxic T cells (CD8 positive lymphocytes). Parenchymal destruction (emphysema) in COPD is associated with loss of lung tissue elasticity, and small airways collapse during exhalation. The precise definition of chronic airflow limitation is affected by age; a fixed cut-off of forced expiratory volume in 1 second/forced vital capacity leads to overdiagnosis of COPD in the elderly. Traditional approaches to distinguishing between asthma and COPD have highlighted age of onset, variability of symptoms, reversibility of airflow limitation, and atopy. Each of these is associated with error due to overlap and convergence of clinical characteristics. The management of chronic stable asthma and COPD is similarly convergent. New approaches to the management of obstructive airway diseases in adults have been proposed based on inflammometry and also multidimensional assessment, which focuses on the four domains of the airways, comorbidity, self-management, and risk factors. Short-acting beta-agonists provide effective symptom relief in airway diseases. Inhalers combining a long-acting beta-agonist and corticosteroid are now widely used for both asthma and COPD. Written action plans are a cornerstone of asthma management although evidence for self-management in COPD is less compelling.

The current management of chronic asthma in adults is based on achieving and maintaining control through step-up and step-down approaches, but further trials of back-titration in COPD are required before a similar approach can be endorsed. Long-acting inhaled anticholinergic medications are particularly useful in COPD. Other distinctive features of management include pulmonary rehabilitation, home oxygen, and end of life care.

Lire la suite...

Related Articles

Infection with the human immunodeficiency virus (HIV) causes systemic T-cell destruction and reduced cell-mediated immunity that leads to a wide range of opportunistic infections and cancers. Secondly, it directly damages many tissues - gut, brain, lung - through mononuclear cell infection and activation.

Thirdly, through immune activation and effects on endothelia, it can cause more subtle systemic organ damage, such as chronic cardiovascular, hepatic, pulmonary and central nervous system disease. Antiretroviral treatment has enabled HIV-infected persons to live with chronic infection, although with some side effects and mortality, including reactions due to the immune reconstitution inflammatory syndrome (IRIS). As cohorts of infected people get older, age-related diseases will combine with chronic HIV infection to produce disabilities whose scale is not yet understood. HIV is detectable in tissues by immunohistochemistry when infection loads are high, such as at first presentation.

Pathologists should proactively consider HIV disease in routine diagnostic work, so as to identify more HIV-infected patients and enable their optimal management.

Lire la suite...