The effects of an epithelial barrier protective cationic aerosol on allergen‐induced airway inflammation in asthma: a randomized, placebo‐controlled clinical trial

Abstract

Inhaled cationic airway lining modulator (iCALM) is a cationic aerosol therapy comprised of 1.29% calcium chloride dissolved in 0.9% isotonic saline that enhances the biophysical barrier function of the airway lining fluid and primes the host defense response. It's ability to attenuate bronchitis caused by inhaled particles was investigated using an allergen-inhalation model in a proof-of-concept study. In a randomized, double-blind, placebo-controlled cross-over trial of 6 mild atopic steroid-naïve asthmatic subjects, 3 doses of iCALM were well tolerated and they attenuated allergen-induced increase in sputum eosinophils, and levels of IL-5, MCP-1 and eotaxin. This study provides an opportunity to investigate the role of enhancing epithelial barrier to decrease airway inflammation provoked by inhaled particles in a variety of airway diseases.

Allergen-induced airway responses

“…Although anti-IL-5 antibodies have been reported to effectively reduce eosinophil levels in the circulation and airways, one study of treatment with anti-IL-5 did not show any inhibition of the LAR but did markedly attenuate allergen-induced airway eosinophilia (table 2) [57]. However, blocking receptors Calcium channel blocker [145] Cationic airway lining modulator [146] Heparin disaccharide [147] Cromones [148,149] Nonsteroidal anti-inflammatory drug [129,150] Lysine ASA [151] Synbiotics [152] ω-3 polyunsaturated fatty acids [153] Furosemide [103] CS: corticosteroid; CytLT: cysteinyl leukotriene; NK: neurokinin; COX: cyclo-oxygenase; MAb: monoclonal antibody; IL: interleukin; TSLP: thymic stromal lymphopoietin; PDE: phosphodiesterase; CRTH2: chemoattractant receptor-homologous molecule expressed on type 2 helper T-cells; IL-4R: IL-4 receptor; VLA: very late antigen; TNF: tumour necrosis factor; Bc: common β-chain; PPAR: peroxisome proliferator-activated receptor; ASA: acetylsalicylate.…”

Revisiting the Role of Eotaxin-1/CCL11 in Psychiatric Disorders

“…PET analysis of beta-amyloid and tau burden). For example, eotaxin-1/CCL11 has been used as a biomarker in clinical trials in asthma ( 50 , 51 ).…”

How does allergen immunotherapy‐induced tolerance improve the airway epithelial barrier function: A mechanistical‐driven hypothesis

“…Other trials have also investigated the potential of enhancing the epithelial barrier to reduce airway inflammation caused by inhaled particles. For instance, a cross‐over double‐blind, randomized controlled trial involving six mild atopic steroid‐naïve asthmatic subjects demonstrated that three doses of an inhaled cationic airway lining modulator had well‐tolerated effects, resulting in attenuation of allergen‐induced sputum eosinophils and reduction of IL‐5, MCP‐1, and eotaxin levels 10 . Moreover, a separate study identified the human CST1 protein as an inhibitor of allergenic protease activity, effectively safeguarding the bronchial epithelial barrier in individuals with asthma, and suggesting CST1 as a promising biomarker for asthma control 11 …”