Background. A subset of individuals with allergic asthma develops a late phase response (LPR) to inhaled allergens, which is characterized by a prolonged airway obstruction, airway inflammation and airway hyperresponsiveness. The aim of this study was to identify changes in the plasma proteome and circulating hematopoietic progenitor cells associated with the LPR following an inhaled allergen challenge. Methods. Serial plasma samples from asthmatics undergoing inhaled allergen challenge were analyzed by mass spectrometry and immunosorbent assays. Peripheral blood mononuclear cells were analyzed by flow cytometry. Mass spectrometry data was analyzed using a linear regression to model the relationship between airway obstruction during the LPR and plasma proteome changes. Data from immunosorbent assays was analyzed using linear mixed models. Results. Out of 396 proteins quantified in plasma, 150 showed a statistically significant change 23 h post allergen challenge. Among the most upregulated were three protease inhibitors: alpha-1-antitrypsin, alpha-1-antichymotrypsin and plasma serine protease inhibitor. Altered levels of 13 proteins were associated with the LPR, including increased factor XIII A and a decreased von Willebrand factor. No relationship was found between the LPR and changes in the proportions of classical, intermediate, and non-classical monocytes. Conclusions. Allergic reactions to inhaled allergens in asthmatic subjects was associated with changes in a large proportion of the measured plasma proteome, whereof protease inhibitors showed the largest changes, likely to influence the inflammatory response. Many of the proteins altered in relation to the LPR are associated with coagulation, highlighting potential mechanistic targets for future treatments of type-2 asthma.

Introduction Very preterm birth is associated with lung function impairment later in life, but several aspects have not been studied. We aimed to comprehensively assess lung function at school age in very preterm infants and term controls, with special emphasis on bronchopulmonary dysplasia (BPD), sex and bronchodilator response. Methods At 12 years of age, 136 children born very preterm (85 with and 51 without BPD), and 56 children born at term performed spirometry, body plethysmography, impulse oscillometry, measurement of diffusion capacity and multiple breath washout, before and after bronchodilator inhalation. Results Airway symptoms and a diagnosis of asthma were more common in children born very preterm. These children had more airflow limitation, seen as lower FEV 1 (p<0.001), FEV 1/FVC (p=0.011) and FEF 25-75 (p<0.001), and a higher total and peripheral airway resistance compared to term born controls. There was no difference in total lung capacity, but air trapping and lung clearance index were higher in children born very preterm. Diffusion capacity was lower in children born very preterm, especially in those with a diagnosis of BPD. In most other tests, the differences between preterm-born children with or without BPD were smaller than between children born preterm versus at term. Boys born preterm had more lung function deficits than preterm born girls. In children born very preterm, airway obstruction was to a large extent reversible. Conclusion At 12 years of age, children born very preterm had lower lung function than children born at term in most aspects. Airway obstruction improved markedly after bronchodilator inhalation, and there was only little difference between children with or without BPD.