Safety of research bronchoscopy in mild-moderate and severe asthma

SUMMARY. OBJECTIVES: Fiberoptic bronchoscopy (FB) as a research tool has contributed considerably to the understanding of the pathogenesis of asthma, but there are concerns regarding its safety, especially in patients with severe asthma. The aim of this study was to document safety data on FB and sampling techniques in asthma research. METHODS: A total of 75 subjects (36 mild-moderate asthmatics, 25 severe asthmatics and 14 healthy control subjects), participating in three studies, underwent research FB. Depending on the study, endobronchial and nasal biopsy, bronchioalveolar lavage (BAL) and bronchial brushing were performed, according to established guidelines. Pulmonary function tests were performed prior to bronchoscopy and 2 hours after the procedure. Daily peak expiratory flow (PEF) measurements were recorded 5 days before and 5 days after bronchoscopy in the 30 patients participating in the first two studies. RESULTS: FB was tolerated well. None of the patients or healthy control subjects developed severe adverse reactions during or after bronchoscopy. Only two patients with severe asthma presented mild adverse events; one demonstrated immediate and complete occlusion of the middle lobe segmental bronchial lumen after BAL instillation and another developed mild desaturation (SaO2 91%). There were no significant changes in FEV1 and PEF measurements after bronchoscopy. CONCLUSIONS: Research FB can be performed safely in patients with asthma, including those with severe disease, with careful assessment and adherence to guidelines. Pneumon 2010, 23(1):34-47

Activin-A is overexpressed in severe asthma and is implicated in angiogenic processes

Activin-A is a pleiotropic cytokine that regulates allergic inflammation. Its role in the regulation of angiogenesis, a key feature of airways remodelling in asthma, remains unexplored. Our objective was to investigate the expression of activin-A in asthma and its effects on angiogenesis in vitro.Expression of soluble/immunoreactive activin-A and its receptors was measured in serum, bronchoalveolar lavage fluid (BALF) and endobronchial biopsies from 16 healthy controls, 19 patients with mild/moderate asthma and 22 severely asthmatic patients. In vitro effects of activin-A on baseline and vascular endothelial growth factor (VEGF)-induced human endothelial cell angiogenesis, signalling and cytokine release were compared with BALF concentrations of these cytokines in vivo.Activin-A expression was significantly elevated in serum, BALF and bronchial tissue of the asthmatics, while expression of its protein receptors was reduced. In vitro, activin-A suppressed VEGF-induced endothelial cell proliferation and angiogenesis, inducing autocrine production of anti-angiogenic soluble VEGF receptor (R)1 and interleukin (IL)-18, while reducing production of pro-angiogenic VEGFR2 and IL-17. In parallel, BALF concentrations of soluble VEGFR1 and IL-18 were significantly reduced in severe asthmatics in vivo and inversely correlated with angiogenesis.Activin-A is overexpressed and has anti-angiogenic effects in vitro that are not propagated in vivo, where reduced basal expression of its receptors is observed particularly in severe asthma.</p

Osteopontin has a crucial role in allergic airway disease through regulation of dendritic cell subsets

Osteopontin (Opn) is important for T helper type 1 (TH1) immunity and autoimmunity. However, the role of this cytokine in TH2-mediated allergic disease as well as its effects on primary versus secondary antigenic encounters remain unclear. Here we demonstrate that OPN is expressed in the lungs of asthmatic individuals and that Opn-s, the secreted form of Opn, exerts opposing effects on mouse TH2 effector responses and subsequent allergic airway disease: pro-inflammatory at primary systemic sensitization, and anti-inflammatory during secondary pulmonary antigenic challenge. These effects of Opn-s are mainly mediated by the regulation of TH2-suppressing plasmacytoid dendritic cells (DCs) during primary sensitization and TH2-promoting conventional DCs during secondary antigenic challenge. Therapeutic administration of recombinant Opn during pulmonary secondary antigenic challenge decreased established TH2 responses and protected mice from allergic disease. These effects on TH2 allergic responses suggest that Opn-s is an important therapeutic target and provide new insight into its role in immunity