Alexandra Ek

Fluticasone and budesonide inhibit cytokine release in human lung epithelial cells and alveolar macrophages

Glucocorticoids are potent anti‐inflammatory agents capable of influencing cytokine release in a number of cell types. The aim of the present study was to investigate whether glucocorticoids, frequently used in the treatment of asthma, interfere with cytokine secretion by lung epithelial cells and alveolar macrophages in vitro. Inhalation of swine dust induces airway inflammation with influx of inflammatory cells and release of proinflammatory cytokines in the lungs. Therefore, human lung epithelial cells (A549) and human alveolar macrophages were stimulated with swine dust or lipopolysaccharide (LPS), and the inhibitory effect of budesonide and fluticasone propionate on cytokine release was studied in a dose‐response (10−13–10−8 M) manner. The time course for the steroid effect was also investigated. Both steroids caused a dose‐dependent, almost total, inhibition of swine dust‐induced IL‐6 and IL‐8 release from epithelial cells and LPS‐induced IL‐6 and TNF‐α from alveolar macrophages. The steroids only partially inhibited IL‐8 release from alveolar macrophages. Budesonide was approximately 10 times less potent than fluticasone propionate. Preincubation with the steroids did not inhibit cytokine release more than simultaneous incubation with stimulus and steroid. In conclusion, budesonide and fluticasone propionate, in concentrations that probably occur in the airway lining fluid during inhalational therapy, inhibited cytokine release from human lung epithelial cells (IL‐6, IL‐8) and alveolar macrophages (TNF‐α, IL‐6, IL‐8). In vitro, the onset of this effect was rapid.

Chronic rhinosinusitis in asthma is a negative predictor of quality of life: results from the Swedish GA(2)LEN survey.

Asthma and chronic rhinosinusitis (CRS) both impair quality of life, but the quality‐of‐life impact of comorbid asthma and CRS is poorly known. The aim of this study was to evaluate the impact of CRS and other relevant factors on quality of life in asthmatic subjects.

Organic dust activates NF-κB in lung epithelial cells

Exposure in swine confinement facilities induces airway inflammation in healthy subjects. The aim of the present study was to elucidate the role of nuclear factor (NF)-kappaB in the inflammatory response induced by organic dust. A human lung epithelial carcinoma cell line (A549) was transfected with reporter genes of the human IL-6 promoter or the NF-kappaB binding site fused to the luciferase reporter gene and stimulated with dust from a swine confinement building. Cytokine release in cell culture supernatants and luciferase activity was measured. The dust-induced the activities of the IL-6 promoter reporter gene and the NF-kappaB reporter gene in parallel with an increase in IL-6 and IL-8 release. The addition of pyrrolidinedithiocarbamate, a chemical NF-kappaB blocking agent, inhibited IL-6 and IL-8 secretion as well as the NF-kappaB reporter gene activity. Increasing the amount of IkappaB alpha led to inhibition of organic dust-induced IL-6 promoter and NF-kappaB reporter gene activities. Fluticasone inhibited the organic dust-induced NF-kappaB activation and IL-6 and IL-8 secretion. Finally, swine dust incubation of A549 cells resulted in a NF-kappaB DNA binding, which is composed of the NF-kappaB1 and RelA proteins. In conclusion, by interference at various levels we have shown that NF-kappaB plays a key role in the inflammatory response to organic dust.

The effect of fluticasone on the airway inflammatory response to organic dust

Exposure to organic dust in a swine house causes acute airway inflammation and increased bronchial responsiveness to methacholine in healthy subjects. The aim of this study was to investigate whether an inhaled glucocorticoid, fluticasone propionate, alters the acute airway responses induced by exposure in a swine barn. In 15 healthy subjects, analysis of nasal lavage fluids, serum samples and bronchial methacholine responsiveness were performed before and after exposure to organic dust in a swine house for 3 h. Seven subjects received fluticasone propionate (500 µg b.i.d. by inhalation and 100 µg intranasally once daily) and eight subjects received placebo during the 2 weeks prior to exposure. Post-exposure plasma interleukin (IL)-6 levels and body temperature were significantly lower in the fluticasone group than in the placebo group. Intranasally administered fluticasone propionate significantly attenuated the plasma protein (assessed as albumin concentrations) leakage and IL-8 and tumour necrosis factor-α response induced by exposure. Fluticasone propionate inhalation exerted no influence on the increased bronchial responsiveness to methacholine induced by exposure. In conclusion, glucocorticoid treatment attenuated the inflammatory response to inhaled organic dust without influencing the increased bronchial responsiveness to methacholine.

Fluticasone and ibuprofen do not add to the effect of salmeterol on organic dust-induced airway inflammation and bronchial hyper-responsiveness

Background.  Exposure in a pig house causes airway inflammation and bronchial hyper‐responsiveness which are not influenced by anti‐asthma drugs, including a β2‐agonist (salmeterol).

Serum periostin relates to type‐2 inflammation and lung function in asthma: Data from the large population‐based cohort Swedish GA(2)LEN

Periostin has been suggested as a novel, phenotype‐specific biomarker for asthma driven by type 2 inflammation. However, large studies examining relationships between circulating periostin and patient characteristics are lacking and the suitability of periostin as a biomarker in asthma remains unclear.

Quality of life in relation to the traffic pollution indicators NO2 and NOx: results from the Swedish GA2LEN survey

Background Asthma is a chronic disease that may affect daily activities and quality of life. Asthmatics have higher incidence of chronic rhinosinusitis (CRS) and asthma is associated with sinonasal inflammation and nasal symptoms, that all impair quality of life. Worsening of asthma has been found associated with levels of nitrogen dioxide as traffic indicator. Aims The aim of the study was to evaluate the impact of traffic pollution indicated by nitrogen oxides (NO2 and NOx) on quality of life in asthmatic persons, individuals with CRS and controls. Methods Within the Swedish Ga2len (Global Allergy and Asthma European Network), 605 asthmatics with and without CRS, 110 individuals with CRS only and 226 controls from four cities were surveyed. The mini Asthma Quality of life Questionnaire (mAQLQ) and the Euro Quality of Life (EQ-5D) health questionnaire were used. Air pollution concentrations at the home address were modelled using dispersion models. Results Levels of NO2 (geometric mean 10.1 μg/m3 (95% CI 9.80 to 10.5) and NOx (12.1 μg/m3, 11.7 to 12.6) were similar among conditions (controls, asthmatics, individuals with CRS and asthmatics with CRS). The mAQLQ overall score was not found associated with levels of NO2 or NOx, with or without adjustments, and neither was scores within each of the four domains of mAQLQ: symptoms, activity limitations, emotional functions and effects of environmental stimuli. The mean EQ-5D index value, based on the five dimensions mobility, self-care, usual activities, pain/discomfort and anxiety depression, was also found unrelated to NO2 and NOx. Conclusions At moderate exposure levels traffic pollution appears not to affect quality of life.