Quantitative Computed Tomography Measurement of Cross-Sectional Area of Small Pulmonary Vessels in Asthmatic Patients
Bronchial asthma is a common respiratory disease characterized by chronic inflammation of the airways, involving various inflammatory cells and cytokines. Its incidence and prevalence have been increasing globally. Asthma is a heterogeneous disease, with different phenotypes based on airway inflammation types, clinical manifestations, predisposing factors, severity, and response to treatment. Small pulmonary vascular alterations are a recognized feature of chronic airway diseases, including asthma, although the underlying mechanisms remain unclear.
Computed tomography (CT) is a widely used imaging technique for evaluating airways and peripheral pulmonary vessels. The cross-sectional area (CSA) of small pulmonary vessels, measured quantitatively on chest CT, has been shown to be a reliable parameter for assessing vascular changes in chronic obstructive pulmonary disease (COPD). Specifically, the CSA of small pulmonary vessels less than 5 mm² (CSA<5) at the sub-subsegmental level has been used to evaluate pulmonary vessel alterations. In COPD patients, the percentage of total CSA<5 for the lung area (%CSA<5) correlates positively with forced expiratory volume in 1 second to forced vital capacity ratio (FEV1/FVC), even in non-smokers without airflow limitation. However, similar research in asthma is limited.
This study aimed to evaluate the correlation between %CSA<5 and airflow obstruction parameters in asthma patients. Additionally, it sought to measure differences in vascular alterations between asthma phenotypes and assess their relationship with cytokine levels. The study enrolled 20 adult asthmatic patients (13 women, age range 26–80 years) and 20 healthy controls (8 women, age range 23–61 years) from Peking University Third Hospital. The diagnosis of asthma was based on the Global Initiative for Asthma (GINA) definition. Exclusion criteria included acute asthma exacerbations, COPD, bronchiectasis, interstitial lung disease, pneumonia, cancer, severe cardiovascular disease, or heart failure.
Participants underwent multi-slice CT scanning using a 64-slice CT scanner (Discovery 750 HD; GE Healthcare, Madison, WI, USA). The scanning parameters included 120 kV, 125–210 mAs, and a reconstruction slice thickness of 0.625 mm. Three CT slices were selected for analysis: one approximately 1 cm above the upper margin of the aortic arch (upper lung field), one approximately 1 cm below the carina (middle lung field), and one approximately 1 cm below the right inferior pulmonary vein (lower lung field). The CSA<5 of pulmonary vessels was measured using ImageJ software, and %CSA<5 was calculated as the percentage of total CSA<5 for the lung area.
Sixth-generation airway parameters, including luminal diameter (LD), inner luminal area (Ai), and airway wall thickness (WT), were measured using Airway Analysis software (Thoracic VCAR; GE Healthcare). The percentage wall area (WA%) was calculated as (wall area/total airway area) × 100. These parameters were corrected for body surface area to obtain corrected LD (LDcor), Ai (Aicor), and WT (WTcor). Pulmonary function tests were performed using lung plethysmography, and induced sputum cytology was conducted to analyze cell differentials and supernatant cytokine levels. Serum levels of leptin, total immunoglobulin E (IgE), periostin, and transforming growth factor β1 (TGF-β1) were measured using enzyme-linked immunosorbent assay (ELISA), while matrix metalloproteinase 9 (MMP-9) was assayed in sputum supernatant.
The results showed no significant difference in %CSA<5 between asthma patients and healthy controls. However, in asthma patients, %CSA<5 was significantly lower in those with an initial onset age of ≤12 years, airflow restriction, and uncontrolled GINA classification. %CSA<5 was positively correlated with FEV1/FVC, FEV1%, LDcor, Aicor, and serum leptin levels, and negatively correlated with total lung WA%. These findings suggest that %CSA<5 of pulmonary small vessels is well correlated with airflow limitation indexes and sixth-generation airway parameters, and it may have clinical significance in predicting asthma control.
The study also examined the levels of inflammatory cytokines in asthma patients. Serum leptin levels were positively correlated with %CSA<5, but no significant correlations were found with other cytokines, including total IgE, periostin, TGF-β1, or MMP-9. Leptin, a hormone produced by adipose tissue, has been implicated in asthma pathogenesis and vascular remodeling. Previous studies have shown that leptin enhances airway responsiveness and promotes neointima formation in vascular smooth muscle cells through the oxidative stress-PI3K/Akt pathway. The positive correlation between serum leptin levels and %CSA<5 in this study suggests that leptin may play a role in pulmonary vascular alterations in asthma.
The study’s findings on sixth-generation airway parameters further support the relationship between pulmonary vascular alterations and airflow limitation in asthma. LDcor and Aicor, which reflect the size of the sixth-generation airway cavity, were positively correlated with %CSA<5, while WA%, which reflects airway wall area, was negatively correlated with %CSA<5. These results indicate that the larger the airway cavity, the better the gas exchange and the larger the CSA of small pulmonary vessels. Conversely, a thicker airway wall is associated with more severe airflow restriction and greater destruction of the small pulmonary vascular bed, leading to a smaller CSA of pulmonary small vessels.
Despite these significant findings, the study has several limitations. The sample size was relatively small, with only 20 asthma patients included in the final analysis. This may have introduced selection bias and limited the generalizability of the results. Additionally, the study excluded patients with acute asthma exacerbations, which may have provided further insights into the relationship between pulmonary vascular alterations and asthma severity. The CSA measurement may also have been affected by the automatic exposure control of the CT scanner, and the lack of histological confirmation of CSA measurements could have introduced discrepancies between CT-based and actual CSA values.
In conclusion, this study demonstrates that %CSA<5 of pulmonary small vessels is well correlated with airflow limitation indexes and sixth-generation airway parameters in asthma patients. It may serve as a new clinical indicator reflecting the degree of airflow limitation and has potential in predicting asthma control. The positive correlation between %CSA<5 and serum leptin levels suggests that leptin may play a role in pulmonary vascular alterations in asthma. Further research with larger sample sizes and histological confirmation of CSA measurements is needed to validate these findings and explore the underlying mechanisms of pulmonary vascular alterations in asthma.
doi.org/10.1097/CM9.0000000000000367
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