Table 3.
Changes in small airway inflammation and function as described in studies on extrafine particle sizes of ICS
| Authors | Subjects | Treatment | Period | Assessment methods | Outcomes |
|---|---|---|---|---|---|
| Micheletto et al30 | 15 mild asthma (steroid-naïve) | CFC-BDP 1000 μg (n = 8) versus HFA-BDP 400 μg (n = 7) | 12 weeks | MCh challenge | Greater increase in PD20 FEV1 to MCh while treated with HFA-BDP. |
| Hauber et al34 | 12 mild-to-moderate asthma | HFA-flunisolide 340 μg bid | 6 weeks | Transbronchial and endobronchial biopsies | Reduction in eosinophils, IL-5, and eotaxin, increase in neutrophils, no change in lymphocytes either in peripheral or central airways. Improvement in lung function. |
| Bergeron et al76 | 12 mild-to-moderate asthma | HFA-flunisolide 340 μg bid | 6 weeks | Transbronchial and endobronchial biopsies | Decrease in α-smooth muscle actin area in peripheral airways, which correlates with the percentage increase in FEF25%–75%. No changes in collagen deposition and TGF-β expression. |
| Ohbayashi77 | 74 moderate stable asthma | FP (n = 37) or BUD (n = 37), then switch to HFA-BDP | One year | Induced sputum | Fewer eosinophil-positive patients in both groups and reduction in sputum ECP and eotaxin. |
| Hoshino78 | 30 mild asthma | Ciclesonide 200 μg versus FP 200 μg |
8 weeks | IOS Induced sputum |
Ciclesonide improved resistance of small airways (R5–R20), distal reactance, reactance area, decreased late-phase sputum eosinophils, increased ACT scores and decreased rescue β2 inhalation compared with FP. No changes in spirometry indices in either group. |
| Cohen et al79 | 16 mild-to-moderate asthma | Ciclesonide 320 μg (n = 9) versus placebo (n = 7) | 5 weeks | HRCT SBNW test CA(NO) |
Improvements in CA(NO) and MCh-induced air trapping on HRCT as compared with placebo. No changes in other small airways parameters. |
| Goldin et al80 | 31 mild-to-moderate asthma (steroid-naïve) | CFC-BDP 100 μg bid versus HFA-BDP 100 μg bid | 4 weeks | HRCT | Greater improvement in air trapping, and less marked increase in MCh-induced air trapping in the HFA-BDP group. Similar improvements in symptoms, spirometry, and PC20 MCh. |
| Tunon-de-Lara et al81 | 25 mild-to-moderate uncontrolled asthma | FP 250 μg bid versus HFA-BDP 200 μg bid | 3 months | HRCT | Similar improvements in air trapping. |
| Yamaguchi et al82 | 38 mild-to-moderate asthma (steroid-naïve) | HFA-BDP 200 μg bid (n = 26) versus CFC-BDP 400 μg bid (n = 12) | 12 weeks | IOS MCh challenge |
Greater improvements in the resistance of small airways (R5–R20) and reactance area (AX) while treated with HFA-BDP. HFA-BDP attenuated MCh sensitivity. |
| Thongngarm et al83 | 30 uncontrolled asthma | HFA-BDP 160 μg bid (n = 20) versus CFC-FP 330 μg (n = 10) in addition to the previous treatment (moderate to high doses of ICS and other controller medications) | 3 months | SBNW test | Greater improvements in CV, CV/VC and postbronchodilator FEF25%–75% while treated with HFA-BDP. |
| Verbanck et al84 | 30 stable asthma (wide range of severity) | BUD, then switch to HFA-BDP (the same dose for 6 weeks, then half dose for another 6 weeks) | 12 weeks | MBNW test | With the switch to HFA-BDP, improvements in Sacin and RV in the subgroup of patients with abnormal baseline Sacin (n = 16) occurred. Although all patients presented abnormal baseline Scond, no changes were observed in this lung zone. |
Abbreviations: CFC, chlorofluorocarbon; BDP, beclomethasone dipropionate; HFA, hydrofluoroalkane; MCh, methacholine; PD20 FEV1, dose of methacholine required to produce a 20% fall in the forced expiratory volume in one second; bid, twice a day; IL-5, interleukin-5; FP, fluticasone propionate; HRCT, high-resolution computed tomography scan; FEF25%–75%, forced expiratory flow at 25%–75% of forced vital capacity; TGF-β, transforming growth factor beta; BUD, budesonide; ECP, eosinophil cationic protein; IOS, impulse oscillometry; R5–R20, resistance from 5 to 20 Hz; X5, reactance at 5 Hz; AX, reactance area; ACT, Asthma Control Test; SBNW, single-breath nitrogen washout; CA(NO), alveolar concentration of nitric oxide; PC20 MCh, the provocation concentration of methacholine causing a 20% reduction in FEV1; ICS, inhaled corticosteroids; CV, closing volume; VC, vital capacity; MBNW, multiple-breath nitrogen washout; Sacin, index of acinar airways ventilation heterogeneity; RV, residual volume; Scond, index of conductive airways ventilation heterogeneity.