[Airway remodeling assessed by high-resolution computed tomography in patients with asthma: relationship to biological markers in induced sputum].

OBJECTIVE

To explore the significance of assessing asthma control by high-resolution computed tomography (HRCT) and biological markers in induced sputum.

METHODS

Forty-eight patients with asthma (asthma group) and 10 healthy subjects (control group) were retrospectively analyzed. The asthma patients were divided into 4 groups based on severity: 6 with near-fatal attacks, 12 with severe, 14 with moderate and 16 with mild asthma. These patients received step therapy for 6 months based on the guidelines for the prevention and treatment of asthma. After achieving asthma control or partial control, HRCT, lung function and cytokine levels in induced sputum were measured. The ratio of wall area to total airway area (WA%), the ratio of 2 airway wall thickness to outer diameter (2T/D) and lung densities in both the inspiratory and expiratory phases were measured. Matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinases-1 (TIMP-1), and transformation growth factor-β(1) (TGF-β(1)) levels in the sputum were assessed by enzyme-linked immunosorbent assay.

RESULTS

There were significant differences in forced vital capacity and forced expiratory volume in 1 second as the percentage of predicted value (FVC% and FEV(1)%, respectively), the ratio of FEV(1)/FVC, and diffusing capacity of the lung for carbon monoxide (D(LCO)) among groups (F = 5.526, 15.064, 16.326, 2.945, respectively, P < 0.05). Sputum levels of MMP-9, TIMP-1 and TGF-β(1) were significantly increased in the near-fatal asthma, severe asthma, moderate asthma and mild asthma groups [MMP-9: (80 ± 16), (70 ± 9), (59 ± 6), and (52 ± 7) µg/L, respectively; TIMP-1: (212 ± 95), (258 ± 167), (28 ± 51), and 98 ± 60 µg/L, respectively; TGF-β(1): (586 ± 81), (513 ± 54), (401 ± 45) and (351 ± 57) µg/L, respectively]compared with the control group [MMP9: (46 ± 5) µg/L; TIMP: (19 ± 13) µg/L; and TGF-β(1): (258 ± 29) µg/L]. These parameters were progressively increased in the asthma groups with the severity of disease (F = 11.179, 49.914, 9.286, respectively, P < 0.05). The ratio of MMP-9/TIMP-1 in sputum was decreased in the near-fatal attack, severe, moderate and mild asthma groups (0.50 ± 0.28, 0.34 ± 0.13, 0.53 ± 0.22, and 0.87 ± 0.75, respectively) compared with the control group (2.93 ± 1.13). The MMP-9/TIMP-1 ratio in the severe asthma group was lowest among the asthma groups (F = 43.335, P < 0.05). 2T/D and WA% were higher in both the near-fatal asthma group (0.51 ± 0.01 and 0.75 ± 0.01, respectively) and the severe asthma group (0.53 ± 0.03 and 0.77 ± 0.03, respectively) as compared to the moderate asthma group (0.43 ± 0.04 and 0.67 ± 0.04, respectively) or the mild group (0.42 ± 0.04 and 0.66 ± 0.04, respectively). 2T/D and WA% were higher in the asthma groups than in the control group (0.35 ± 0.03 and 0.57 ± 0.04, respectively), (F = 40.224, 41.294, respectively, P < 0.05). Lung densities in both the inspiratory and expiratory phases were lower in the near-fatal attack group as compared to those in the other asthma groups or the control group; and the lung density differences between the two phases in the near-fatal attack group were smaller than those in the other asthma groups or the control group (F = 5.048, 13.247, 11.541, respectively, P < 0.05). 2T/D and WA% were correlated positively with MMP-9, TIMP-1 and TGF-β(1) levels, but negatively with the MMP-9/TIMP-1 ratio, respectively.

CONCLUSIONS

HRCT and biological markers in induced sputum could be used to accurately evaluate asthma control. These findings suggest that the severity of asthma, especially, near-fatal attack of asthma, is correlated not only with the degree of airway remodeling, but also with the degree of air trapping.