Baseline clinical characteristics
Twenty-four consecutive patients with severe asthma were enrolled in this study but 3 patients were withdrawn from the analysis as they were unable to successfully complete the MBNW test at baseline. The remaining 21 patients, 9 males, 12 females, had a mean age of 56.0±14.3years, and body mass index of 31.6±7.0 kg/m2. The mean ACQ score was 3.4±0.8. In the six months prior to BT, patients experienced an average of 3.1±2.9 exacerbations requiring oral corticosteroids. The mean beclomethasone equivalent daily dose of inhaled corticosteroids was 1704±911 ug. Fifteen patients were taking maintenance oral corticosteroids, and the mean prednisolone dose for the whole group of 21 patients was 12.5±15.4 mg/day. All patients were using dual long acting bronchodilators. Patients used an average of 13.0±10.4 puffs/day of short acting beta-2 agonist reliever medication. The mean peripheral blood eosinophil count was 100±100 cells/ul, and the median IgE was 41 (Interquartile range 11-181) IU/ml. Twelve patients (57%) were never smokers, and there were no current smokers. The mean CT derived emphysema score was 2.2±4.0% (measured at –950 Hounsfield units). The mean Forced Expiratory Volume in 1-second (FEV1) was 45.6±12.9% predicted and the mean Diffusion Capacity per unit lung volume was 92.8±27.8% predicted.
The response to treatment measured by clinical parameters is demonstrated in Figure 1. The ACQ fell from 3.4±0.8 at baseline, to 2.0±1.2 six weeks after BT treatment was completed, and 2.0±1.1 at the six-month reassessment (p<0.001) - a difference of almost 3 times the minimal clinically significant change . Four patients failed to achieve an improvement in ACQ of 0.5, and hence the overall group response rate measured by ACQ was 81%.
The exacerbation rate in the 6 months following completion of BT was 1.4±1.7, compared to 3.1±2.9 at baseline (p<0.001). The group mean daily requirement for prednisolone fell from 12.5±15.4 mg/day to 5.5±7.8 mg/day (p=0.001). The usage of short acting beta-agonist reliever treatment fell from 13.0±10.4 to 5.2±6.7 puffs/day (p<0.001).
Response to treatment: spirometry and plethysmography
The outcomes of BT measured by lung function tests are presented in Table 1. In these patients, a significant increase in prebronchodilator FEV1 was observed 6 months after BT, amounting to 170±290 mls, or an increase of 12.6%. An increase in Vital Capacity (VC) was also observed, but to a smaller degree (7%). The Total Lung Capacity was unaltered by BT. Consistent with an increase in VC, a significant reduction in Residual Volume was observed. There was a substantial reduction (28%) in plethysmographically determined Total Airway Resistance after BT. The Specific Airway Resistance (sRaw) fell to a similar degree, demonstrating that the improvement in Raw did not relate to changes in lung volume.
Response to treatment: MBNW
At baseline, in this group of severely obstructed asthmatic patients, the LCI was prolonged at 12.7±3.3, or 187±63% of predicted values. In other words, owing to ventilation inhomogeneity, it took almost twice as long as in a healthy lung to clear the tracer gas. Following BT, a 7% improvement in LCI was observed, to 11.8±2.4 (p=0.049), indicating more homogeneous ventilation was occurring within the lung.
The phase III slope parameters were both elevated at baseline consistent with the ventilation heterogeneity demonstrated by the LCI. The Scond was 180% of the predicted value, or similar to the increase in LCI, but the mean Sacin was increased to 4 times the normal predicted value . It is clear from Table 1 that there was no change in Scond following BT, but there was a trend towards improvement in Sacin. Sacin is thought to reflect diffusion dependent acinar regions of the lung. Reductions in Sacin in asthma are observed following bronchodilators, and with improved asthma control using inhaled steroids .
The validity of the MBNW measurements was examined by comparing the measurement of FRC made with the MBNW system, with the measurements in the plethysmograph. For 63 pairs of measurements (21 patients at 3 timepoints), the Pearson Correlation was 0.65 (p=0.001). The FRC measurements made in the plethysmograph were higher than in the MBNW system: 3.46±1.00 litres by plethysmograph compared to 3.00±0.88 litres by MBNW (p=0.001). This technique related difference has been previously recognized .
Using Pearson correlation, the potential relationship between the changes in airway resistance (Raw) and changes in LCI, from baseline to 6 months, were examined, and a significant positive correlation was demonstrated (r=0.46, p=0.035) suggesting the two indices are interdependent (Figure 2). The change in LCI was also compared with the change in ACQ (r=0.41, p=0.068) (Figure 3). Although this latter correlation did not achieve statistical significance, Figure 3 demonstrates that each patient who experienced an improvement in LCI after BT, also demonstrated an improvement in ACQ. Furthermore, the three patients in whom the ACQ deteriorated after BT, also had a deterioration in LCI.
Response to treatment measured by CT scanning
Using the described CT scanning method, the volume of air was measured in the airways distal to the lobar orifice, since these are the airways potentially treated during BT. Estimations were made both at TLC and at FRC, and for the right and left lungs. Figure 4 shows the airway volume at baseline, and then again after the left lung has been treated by BT. As expected, on the right side, no changes were observed with time. On the left side, where the airway volume is smaller at baseline owing to fewer bronchopulmonary segments, the distal airway volume increased after BT from 5.1±1.9 mls to 6.3±2.7 mls at TLC (p=0.009), and from 2.5±1.0 mls to 3.1±1.3 at FRC (p=0.004).