High resolution computerized tomography of the chest and pulmonary function testing in evaluating the effect of tobramycin solution for inhalation in cystic fibrosis patients.

To evaluate the sensitivity of high-resolution computerized tomography (HRCT) of the chest compared to spirometry measures in evaluating the effects of tobramycin solution for inhalation (TSI) in cystic fibrosis (CF) patients.Thirty-two subjects >/=6 years old with mild to moderate CF lung disease were enrolled in a randomized, double-blind, placebo-controlled pilot study. Duration was 28 days; 31 subjects completed the study.HRCT scores decreased 4.06 +/- 3.20 (mean +/- SD) for TSI and decreased 0.17 +/- 1.78 for placebo subjects (P = 0.13). Mean forced expiratory flow during middle half of forced vital capacity (FEF(25%-75%)) predicted increased 6.08 +/- 4.86 for TSI and decreased 0.60 +/- 2.34 for placebo (P = 0.23). Percentage forced expiratory volume in 1 s (FEV(1)) predicted increased slightly for both TSI and placebo (1.29 +/- 3.33 for TSI and 1.17 +/- 1.4 for placebo) (P = 0.97). Two of eight HRCT component scores (atelectasis and inhomogeneity) were observed to be highly discordant with observed HRCT global total score and other HRCT component scores. A modified total score was calculated by dropping them from the global total score. The modified HRCT total scores decreased 6.68 +/- 3.09 for TSI subjects and increased 0.02 +/- 2.0 for the placebo subjects (P = 0.07). Sample sizes were calculated to show statistical significance by differences in modified total HRCT scores, global total HRCT scores, FEF(25%-75%) predicted or FEV(1) % predicted. A total of 60, 100, 200, and over 800 patients would be necessary respectively.HRCT can be a useful measure of change in CF pulmonary disease, requiring a smaller sample size than that required to show treatment effect by pulmonary function testing (PFT) alone.

The use of high resolution computerized tomography (HRCT) of the chest in evaluating the effect of tobramycin solution for inhalation in cystic fibrosis lung disease.

OBJECTIVES: To compare the usefulness of HRCT of the chest versus spirometric measures (PFTs) in evaluating the effect of tobramycin solution for inhalation (TSI) in cystic fibrosis (CF). METHODS: Thirty-two CF patients with mostly mild lung disease age > or = 6 years, were enrolled in a double-blind, placebo-controlled pilot study. Patients were chronically colonized with Pseudomonas aeruginosa for at least 6 months prior to and at enrollment. If patients were on TSI, they were taken off for at least 3 months prior to enrollment. Duration was 6 months; 31 subjects completed the study. HRCT and PFTs were evaluated at baseline, after 28 days of treatment and at the end of the study. Study medication was administered as 5 ml nebulized treatment twice a day for 28 days followed by 28 days off (one cycle). Study consisted of three cycles. Two radiologists scored all films using a validated system. A total HRCT score consists of the sum of subscores: linear opacities, hyperinflation, nodular opacities, peribronchial thickening, mucous plugging, and bronchiectasis; each subscore could range from 0 to 80, with potential total scores varying from 0 to 480. The percent of the maximum possible HRCT score was then calculated and used for all comparisons. RESULTS: Using two tailed paired t-test, the percent maximum HRCT score decreased by 1.4 +/- 2.6% (mean +/- SD) (P = 0.049) and 0.3 +/- 2.8% (P = 0.63) for the TSI group and decreased by 0.1 +/- 1.5% (P = 0.74) and increased by 0.6 +/- 1.8% (P = 0.23) for the placebo group between visits 1 and 2, and visits 1 and 3, respectively. The data were then analyzed using a mixed model utilizing changes in scores over the durations of the study for each group. The change of HRCT score for the TSI group was -0.24/day (P = 0.02) and -0.03/day (P = 0.22), and for the control group the change was -0.01 (P = 0.93) and 0.02 (P = 0.29) between visits 1 and 2, and visits 1 and 3 respectively. FEF(25-75)% and FEV(1)% changes were not statistically significant using both analyses. CONCLUSION: HRCT seems to be more sensitive in detecting treatment effect than PFT in CF patients with mild lung disease, especially following the first treatment period (visit 2). Total HRCT score showed some improvement at the end of the study, though not statistically significant. This is probably due to obtaining the HRCT an average of 30 days after completion of the TSI treatment, and selection of study population with mostly mild lung disease. This could indicate that the most significant improvement in the total HRCT score in this patient population occurs after the first treatment period with TSI.