Neural signature of attention impairment in allergic asthma: an ERP study

Background Cognitive impairments are linked to poor treatment response and disease control in allergic asthma. However, there are no studies exploring attention-related functional brain alterations in allergic asthma. Here, we explore attention deficit and its association with clinical characteristics and common neuropsychiatric disorders in patients with allergic asthma. Methods We recruited 38 participants, equally distributed into healthy and asthma groups. Behavioral, neurophysiological, and lung function assessment tools were used in this study. Results Our behavioral data show that allergic asthma induces attention impairment. Additionally, the event-related potentials (ERP) analysis reveals that this attention deficit is associated with a disruption in cognitive processing capability in frontal brain areas. These behavioral and neurophysiological abnormalities were strongly correlated with disease severity and neuropsychiatric comorbidities of asthmatic patients. Conclusion Together, here we propose that disrupted neurophysiological responses in frontal brain areas might lead to attention impairments in patients with allergic asthma. These findings could help characterizing the neuro-pathophysiology of cognitive disorders in allergic asthma, possibly opening the way for development of novel treatment strategies.</p

Effects of <i>L</i>. <i>rhamnosus</i> (LR) and <i>B</i>. <i>breve</i> (BB) on the release of cytokines induced by cigarette smoke extract (CSE).

<p>THP-1 cells (1x10⁶/ml) were preincubated for 2h with LR or BB (both at 10 bacteria/cell) in the presence or absence of 1.5% CSE and the release of IL-23 (A), IL-10 (B), IL-1β (C), TNF-α (D) and IL-6 (E) assessed after 16hrs. Data are presented as mean ± S.E.M. of three independent experiments. *p < 0.05; **p < 0.01 versus control and ^#p<0.05 versus CSE-stimulated mediator release.</p

THP-1 cells efficiently phagocytose FITC-labeled-<i>L. rhamnosus</i> and <i>B. breve</i>.

<p>Data are presented as median (95% confidence intervals) of n = 4 independent experiments.</p><p>THP-1 cells efficiently phagocytose FITC-labeled-<i>L. rhamnosus</i> and <i>B. breve</i>.</p

The effect of <i>L</i>. <i>rahmonusus (</i>LR<i>) and B</i>. <i>breve</i> (BB) on cigarette smoke extract (CSE)-, lipopolysaccharide (LPS)- and CpG-induced CXCL-8 release by THP-1 macrophages.

<p>Cells 1x10⁶/ml were pretreated for 2hrs with 10 bacteria/cell (1), 20 bacteria/cell (2) and 50 bacteria/cell (3) LR and BB in the presence and absence of 1.5% CSE and CXCL-8 release (A) and mRNA expression (B) determined after 16 and 3hrs respectively. Expression of CXCL-8 mRNA is expressed as a ratio of the housekeeping gene GAPDH. Cell viability as assessed by Annexin V expression was not affected by any treatment (C). A similar effect of LR and BB on (D) LPS (1000ng/ml)-and (E) CpG oligonucleotide (3μM)-stimulated CXCL-8 release at 16h was also seen. (F) Cells were preincubated for 2 h with E.coli (at various ratios of bacteria to cells) and then stimulated with 1.5% CSE and CXCL-8 release determined after 16hrs. (G) U937 macrophages were stimulated with LR and BB in the presence and absence of 1.5% CSE and CXCL-8 release determined after 16hrs. Data are presented as mean ± S.E.M. of three independent experiments. *p < 0.05; **p < 0.01 versus control and ^#p<0.05 versus CSE-stimulated CXCL-8.</p

Effects of <i>L</i>. <i>rhamnosus</i> (LR), <i>B</i>. <i>breve</i> (BB) and cigarette smoke extract (CSE) on expression and release of HMGB1.

<p>Cells were preincubated with LR or BB (both at 10 bacteria/cell) for 2h before stimulation with 1.5% CSE for 5h for analysis of intracellular HMGB1 by Western blotting (A) and 16h for detection of HMGB1 release by ELISA (B). A representative blot of the results from 3 independent experiments is shown with histone H1 (H1) as a housekeeping protein. Data in B are presented as the mean±S.E.M. of 3 independent experiments. *p < 0.05; **p < 0.01 versus control and ^#p<0.05, ^##p<0.01 versus CSE-stimulated HMGB1 release.</p

Effects of <i>L</i>. <i>rhamnosus</i> (LR) and <i>B</i>. <i>breve</i> (BB) on cigarette smoke extract (CSE)-induced NF-κB activation.

<p>Cells 5x10⁴ /well were preincubated for 2h with LR or BB (both at 10 bacteria/cell) and then incubated for 24h in the presence or absence of 1.5% CSE. SEAP activity was measured in cell culture supernatant (A). *p<0.05 compared to the control and ^#p< 0.05 compared to CSE alone. The effect of RL and BB on NF-κB p65 nuclear import was also assessed by Western blotting with histone H1 (H1) as a nuclear loading control (B). A representative blot of 3 independent experiments is shown (upper panel) with the mean±S.E.M. data presented graphically (lower panel). *p < 0.05; **p < 0.01 versus control and ^#p<0.05 versus CSE-stimulated p65 nuclear import.</p