*3.4. Systemic Protein Hydroperoxides Generation Was Related to Bronchial Obstruction, Airway Geometry, and Bronchoalveolar Lavage Fluid Biomarkers*

Next, we analyzed associations of systemic oxidative stress measures with clinical characteristics of asthma, lung function, airway remodeling indices, and BAL biomarkers.

Surprisingly, the dynamics of HP generation were not related to the severity of asthma, symptom control, or asthma medications used. However, we detected a weak inverse correlation with airway obstruction spirometry indices (Figure 4).

**Figure 4.** Inverse correlation between hydroperoxide generation in coumarin boronic acid (CBA) assay and lung function; for abbreviations, see the legend in Figure 2 and Table 2.

Furthermore, asthma patients with persistent airflow limitation showed a 19% increase in cumulative HP formation (*p* = 0.02).

Oxidative stress measures were not associated with RBM thickness or collagen I deposit in bronchial biopsy specimens. They were also not directly associated with lung CT parameters. However, multiple regression models showed that WAR or WTR in RB1 could be an independent determinant of higher HP formation dynamics, as presented in Table 3 (a model for the R factor).

**Table 3.** Multiple linear regression model for a relative increase of fluorescent product growth velocity (R factor) in the real-time CBA assay in asthma patients. Presented variables are documented as independent determinants; however, they explain only 16% of the R factor variability.


The resulting standardized regression coefficient (β) with 95% confidence interval (95% CI) for a factor (independent variable) indicates the increase/decrease in standard deviations (SDs) of a dependent variable (R factor) when that particular factor increases by 1 SD and all other variables in the model remain unchanged. Abbreviations: RB1—the right upper lobe apical segmental bronchus; for other abbreviations, see footnote to Table 2.

Among BAL biomarkers, the HP generation was weakly positively associated with the IL-6 and IL-12(p70) concentrations and neutrophil count (Figure 5). Additionally, BAL IL-6 appears to be an independent determinant of higher HP formation, as shown in Table 3.
