Inflammation in asthma: relation to symptomatology, exacerbations and lung function

Sammanfattning: Asthma is an inflammatory disease in the airways. It is characterized by respiratory symptoms such as wheezing, variable airflow obstruction and impaired lung function development. A better understanding of the underlying inflammation is crucial in order to treat and prevent asthma symptoms and lung function deterioration.We have evaluated six inflammatory markers in relation to asthma symptoms, asthma attacks, and lung function measures (fixed airflow obstruction (FAO) and lung function development over time) in five investigations. The markers (elevated levels) were fraction of exhaled NO (FeNO) (elevated ≥25ppb), serum eosinophil cationic protein (S-ECP) (≥20 µg/L), blood eosinophils (B-Eos) (≥300 cells/µL), urinary eosinophil derived neurotoxin (U-EDN) (≥65.95mg/mol creatinine), serum periostin (S-periostin) ( ≥74μg/L), and blood neutrophils (B-Neu) (≥5,100 cells/µL).  The studied populations consisted of mainly adults (except in Paper II) and included asthmatics from the Swedish part of the Global Allergy and Asthma European Network survey (Papers I and III), the American National Health and Nutrition Examination Survey (Papers II and IV), the Uppsala part of the European Community Respiratory Health Survey I-III, the Vlagtwedde and Vlaardingen study, and the Rotterdam study, the latter two from the Netherlands (Paper V). All study populations were population based, and the asthmatics included had mainly mild to moderately severe asthma.The main findings are that simultaneously elevated FeNO and S-ECP are associated with more reported asthma symptoms and attacks, and elevated FeNO and B-Eos are associated with lower lung function, suggesting a value in measuring both local (FeNO) and systemic (S-ECP, B-Eos) inflammation in asthma. Eosinophil inflammation (elevated U-EDN and S-ECP) was associated with FAO in asthma, while the other type-2 markers FeNO and S-periostin were not. Elevated B-Eos was further associated to lower lung function measures in a general population, and a faster lung function decline in asthmatics. FeNO was more often elevated in asthmatics, but was difficult to robustly associate to a specific disease characteristic. B-Neu was associated to FAO in participants with current smoking or pronounced smoking history.In conclusion, asthma with elevated markers for eosinophil inflammation was associated to worse morbidity and lung function development in comparison with asthmatics without elevated markers for eosinophil inflammation. These results indicate ongoing eosinophil inflammation in asthma as closely associated to disease activity and the absence of eosinophil inflammation to less morbidity.