Two Siblings Homozygous for F508del-CFTR Have Varied Disease Phenotypes and Protein Biomarkers

Two siblings with CF are homozygous for F508del (referred to as Subject A and Subject B). Despite having the same CFTR genotype and similar environment, these two subjects exhibited different disease phenotypes. We analyzed their medical records and CF Foundation Registry data and measured inflammatory protein mediators in their sputum samples. Then, we examined the longitudinal relationships between inflammatory markers and disease severity for each subject and compared between them. Subject A presented a more severe disease than Subject B. During the study period, Subject A had two pulmonary exacerbations (PEs) whereas Subject B had one mild PE. The forced expiratory volume in 1 s (FEV1, % predicted) values for Subject A were between 34–45% whereas for Subject B varied between 48–90%. Inflammatory protein mediators associated with neutrophils, Th1, Th2, and Th17 responses were elevated in sputum of Subject A compared with Subject B, and also in samples collected prior to and during PEs for both subjects. Neutrophilic elastase (NE) seemed to be the most informative biomarkers. The infectious burden between these two subjects was different.

PROTEOLYTIC ENZYMES AND CYTOKINES IN CHRONIC BRONCHOPULMONARY DISEASES IN CHILDREN

A total of 288 children with chronic inflammatory diseases of the lung (HIDL), including cystic fibrosis (CF), were examined comprehensively. Significant activation of neutrophilic elastase (NE) in the chronic pulmonary heart (CPH) and an increase in the activity of cathepsin G (according to the activation of anti-cathepsin-G) in CPH patients was established. An increase in the level of matrilysin - matrix metalloproteinase-7 (MMP-7) as the condition worsened was also found in patients with chronic leukemia; A significant increase in the content of MMP-7 is typical not so much for CPH patients, but for СF patients, in particular, during the formation of CPH in them. In СF patients, even without worsening the condition in the form of pulmonary arterial hypertension (PAH), the developing pulmonary heart (DPH) and CPH, the levels of MMP-7 were increased more significantly than in congenital lung malformations cases. In patients with pulmonary arterial hypertension (PAH) grade 1, the levels of IL-4 and IL-6 were 11.1 and 4.4 times higher than in controls, respectively. In PAH grade 2 children, the concentrations of IL-4 and IL-6 were 11.5 and 4.8 times higher than in controls. The dynamics of the content of endothelin-1 in the blood of patients was also characterized by an increase in its concentrations in HIDL patients by 4.5, 2.4 and 4.7 times, respectively, compared with the control. The content of nitric oxide in the blood of PAH patients was significantly lower than in the control and directly depended on the severity of PAH.

Verification of zinc role in pathophysiology of chronic obstructive pulmonary disease

Aim. Determination of the level of zinc and its fractions, as well as the enzyme neutrophilic elastase and albumin in persons suffering from chronic obstructive pulmonary disease (COPD), as well as smoking actively and passively. Materials and methods. The study involved 30 patients with a diagnosis of COPD and 90 healthy persons (60 of them smoking at the present time, 30 - no) who underwent spirometry and determination of zinc levels and its pools, albumin, and neutrophil elastase. All data are subject to statistical processing. Results. It is determined that the studied parameters differ significantly in the groups of smokers with COPD, healthy smokers and non-smokers, and correlate with the volume of forced exhalation for 1 second as a percentage of the due. Conclusion. The revealed regularities make it possible to consider the indicator "share of bound zinc fraction" introduced in the study as a screening criterion in diagnosing COPD in smokers.

Effect of female sex hormones on microbicidal activity of neutrophils

The objective of the present work was to study effects of estradiol and progesterone on enzymatic, oxidative, and phagocytic function of human neutrophils. It was shown that sex hormones applied at the doses equivalent to their concentrations in pregnant women selectively stimulated spontaneous activity of neutrophilic elastase and increased myeloperoxidase enzymatic activity. Neither estradiol nor progesterone had apparent effect on baseline spontaneous hemiluminescence of neutrophils but stimulated E.coli-induced luminol-dependent hemiluminescence. Simultaneously, both steroids inhibited phagocytic activity of these cells. It is concluded that this modulating action of female sex steroids on neutrophil functions is likely to come out during pregnancy.