Table 1 Biological agents and small airway dysfunction (SAD): summary of the main clinical studies performed
Biological agent | Authors (reference) | Patients treated | Diagnostic tool to detect SAD | Main Results or Endpoints | Impact on SAD |
|---|---|---|---|---|---|
OMALIZUMAB | Huang et al. [39] | 124 | FEF 25–75% | improvement in small airway ventilation |  +  +  +  |
Tajiri et al. [40] | 26 | CT scan FEF 25–75% | airway-wall thickness reduced signi-ficantly 48 weeks of omalizumab treatment |  +  +  | |
Paganin et al. [41] | 207 | forced vital capacity (FVC), pre- and postbronchodilator FEV1, residual volume (RV), and total lung capacity (TLC) | After omalizumab, FEV1 improved at 6 months in responder patients and then remained stable for 2 years. RV and RV/TLC improved at 6 months |  +  | |
Saadeh et al. [42] | 12 | IOS, spirometry | IOS indices were significantly improved after 3 to 4 months of treatment; but were not paralleled by changes in FEV1 |  +  +  | |
OMALIZUMAB + MEPOLIZUMAB + BENRALIZUMAB | Chan et al. [43] | IOS, spirometry | FEF25-75% increased significantly in the omalizumab sub-group(15 of 20 patients) but not significantly in the anti-IL5 subgroup (21 of 36 patients). Insufficient evaluable IOS data to perform a meaningful analysis |  +  +  | |
MEPOLIZUMAB | Antonicelli et al. [44] | 18 | Forced Oscillation Technique (FOT) | Statistically FOT parameters improvement after mepolizumab |  +  +  +  |
Sposato et al. [45] | 134 | spirometry | FEV1% and FEF25-75% improved significantly after mepolizumab |  +  +  +  | |
Farah et al. [46] | 20 | spirometry, FeNO, multiple breath nitrogen washout to measure Lung Clearance Index, regional ventilation inhomogeneity in acinar (Sacin) and conducting (Scond) airways | Early improvement in small airway function has been associated with asthma control |  +  +  | |
Yilmaz et al. [47] | 41 | spirometry | not found significant changes in FEV1 and FEF25-75 values at baseline, 12th, 24th, and 52nd weeks | No impact | |
Maglio et al. [48] | 105 | spirometry | significant improvement in FEF25-75% was demonstrated |  +  +  +  | |
DUPILUMAB + MEPOLIZUMAB + BENRALIZUMAB | Abdo et al. [49] | IOS, FEF25-75%, air trapping (RV and RV/ TLC) | Responders had significantly higher baseline FDR (frequency dependence of resistance) compared to partial or non-responders but similar FEV1, FEF25–75, RV and RV/TLC |  +  +  | |
BENRALIZUMAB | Panettieri et al. [50] | 118 | spirometry/whole-body plethysmography | Improvements in FEF25–75% observed for the benralizumab-treated group (but not significant). Improvements in hyper-inflation indices and IC were greater for pts receiving benralizumab vs placebo |  +  +  |
Badal et al. [51] | 12 | spirometry, forced oscillation technique (FOT), multiple breath nitrogen washout (MBNW) | significant improvements in Sacin, X5, and a trend for improvement in Scond |  +  +  +  | |
Mcintosh et al. [52] | 27 | spirometry, IOS, FeNo | X5 and AX were significantly different after benralizumab across subgroups, and both X5 and AX were significantly different after 28-days of benralizumab in the FeNO high subgroup. Clinically relevant ventilation defect percent (VDP) improvements were also observed in the FeNO intermediate and FeNO high sub-groups |  +  +  +  | |
DUPILUMAB | Castro et al. [53] | 1264 | spirometry / FEF25-75% | Improvement not limited to the large airways but also extends to the small airways |  +  +  |
Rabe et al. [54] | 103 | spirometry /FEF25-75% | At Week 24 in the overall population, pre- and post-BD FEV1, FVC, FEV1/FVC and FEF25–75% had improved vs placebo Improvements were early and generally sustained over 24-weeks treatment |  +  +  | |
Pelaia et al. [55] | 20 | spirometry/whole-body plethysmography, FeNO | Dupilumab induced a significant reduction in lung hyperinflation, significant increase in median FEF25–75% |  +  +  +  | |
Minagawa et al. [56] | 62 | spirometry,forced oscillation technique (FOT), FeNO | FEV1, %FEV1, %FVC, improved significantly after three months of dupilumab treatment. FeNO was markedly decreased.. R5, R20, X5, and Fres were significantly correlated with FEV1 before and three months after dupilumab administration |  +  +  +  | |
Bacharier et al.[57] | 236 | Spirometry/FEF25-75% | significant improvements in percent predicted pre-bronchodilator FEV1 and FEF25-75% |  +  +  +  |