In this study, we detected CSA from 20 asthmatic individuals and 20 healthy controls, as well as sixth-generation airway parameters and pulmonary function. Moreover, we examined several inflammatory cytokines in asthma. %CSA<5 was affected by age of asthma onset, airflow limitation, and GINA uncontrolled status. It was correlated with some pulmonary function indexes, airway remodeling indexes and serum leptin level in patients with asthma.
Since CT has been used to detect peripheral pulmonary vessels, studies of the CSA of small pulmonary vessels have focused mainly on COPD and emphysema.[6,9,11,12,15] Previous reports demonstrated a positive correlation of %CSA<5 with FEV1/FVC.[6,9,16] Besides being associated with obstructive ventilatory parameters, %CSA<5 was negatively correlated with thoracic aortic calcification score and pulmonary arterial mean pressure.[7,11] Recent studies have suggested that CSA is negatively correlated with degree of emphysema and frequency of acute exacerbations in patients with COPD. However, to our knowledge, no study has investigated %CSA<5 for pulmonary small vessels in people with asthma.
Leptin production has been demonstrated in human peripheral lung tissue, namely bronchial epithelial cells, alveolar type II pneumocytes, and lung macrophages.[19,20] Numerous studies have shown high expression of serum leptin in asthma and increased with disease exacerbation. Leptin improved serum IgE level and enhanced airway responsiveness in asthmatic mice. Our previous results showed that sex and BMI are important factors affecting serum leptin levels in individuals with asthma. This study suggested that leptin is involved in pulmonary vascular changes of people with asthma. In fact, leptin has a role in vascular remodeling. In the study of leptin-deficient ob/ob mice, exogenous leptin greatly increased neointima formation. Exogenous leptin also enhanced lesion growth and increased cellular proliferation in injured arteries from wild-type mice but had no effect on vessels from leptin receptor–deficient db/db mice, which suggests that leptin promotes neointima formation in a receptor-dependent manner. Experiments in vascular smooth muscle cells suggested that leptin could participate in vascular remodeling and stiffness by extracellular matrix production in the cells via the activation of the oxidative stress–PI3K/Akt pathway and the production of the profibrotic factors TGF-β and connective tissue growth factor. The mechanism of leptin in vascular alteration in asthma needs further studies.
Although quantitative CT measurement is used to check sixth-generation airway and pulmonary vessels, previous studies did not correlate %CSA<5 with airway remodeling indexes. LDcor and Aicor are two parameters that reflect the size of the sixth-generation airway cavity. In this study, they were positively correlated with %CSA<5 of small vessels of the lung: the larger the sixth-generation airway cavity, the larger the CSA of small pulmonary vessels. We presumed that the larger the air chamber, the better the gas exchange and the smaller pulmonary vessels. WA% reflects the airway wall area. A larger airway wall area is associated with more severe airflow obstruction. %CSA<5 was negatively correlated with WA%. We speculate that the thicker the airway wall, the more severe the airflow restriction and the greater the destruction of the small pulmonary vascular bed for therefore smaller CSA of the pulmonary small vessels. These results explained the aforementioned differences between airflow-restricted groups from the anatomic perspective of the airway wall as well as the positive correlation between %CSA<5 and obstructive ventilator indexes. It further supports our hypothesis that pulmonary vascular alteration may reflect the degree of airflow limitation.
There were several limitations to this study. The major one is low sample size. We recruited 78 asthma patients, but only 20 had complete data, including chest CT scan results, induced sputum, and results of cytokine detection, which may imply selection bias. Second, we excluded acute exacerbations of asthma. Further studies could compare each parameter during all clinical stages in asthma. Third, the CSA measurement might have been affected by the automatic exposure control provided by the scanner. Finally, we did not measure the CSA of pulmonary vessels histologically, so CSA measured by CT scan and the actual CSA of pulmonary vessels might differ. Further studies are necessary.
In summary, this study demonstrated that %CSA<5 of pulmonary small vessels correlated well with indexes of airflow limitation in asthma and may be a new clinical indicator reflecting the degree of airflow limitation. Moreover, %CSA<5 has potential to predict the clinical control of asthma.
This work was supported by grants from the National Natural Science Foundation Youth Fund Project (No. 81400017); Beijing Natural Science Foundation (No. 7173273); and National Natural Science Foundation Emergency Management Project (No. 81641153).
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