Inhaled mucoactive agents are used in respiratory disease to improve mucus properties and enhance secretion clearance. The effect of
mannitol, recombinant human
deoxyribonuclease/
dornase alfa (
rhDNase) and hypertonic saline (HS) or
normal saline (NS) are not well described in chronic lung conditions other than
cystic fibrosis (CF). The aim of this review was to determine the benefit and safety of inhaled mucoactive agents outside of CF. We searched Medline, Embase, CINAHL and CENTRAL for randomized controlled trials investigating the effects of mucoactive agents on lung function, adverse events (AEs), health-related quality of life (HRQOL), hospitalization,
length of stay, exacerbations, sputum clearance and
inflammation. There were detrimental effects of
rhDNase in
bronchiectasis, with average declines of 1.9-4.3% in forced expiratory volume in 1 s (FEV1 ) and 3.7-5.4% in forced vital capacity (FVC) (n = 410, two studies), and increased exacerbation risk (relative risk = 1.35, 95% CI = 1.01-1.79 n = 349, one study). Some participants exhibited a reduction in FEV1 (≥10-15%) with mucoactive agents on screening (mannitol = 158 of 1051 participants, rhDNase = 2 of 30, HS = 3 of 80). Most AEs were mild and transient, including
bronchospasm,
cough and
breathlessness. NS eased symptomatic burden in
COPD, while NS and HS improved spirometry, HRQOL and sputum burden in non-CF
bronchiectasis.
Mannitol improved mucociliary clearance in
asthma and
bronchiectasis, while the effects of
N-acetylcysteine were unclear. In chronic
lung diseases outside CF, there are small benefits of
mannitol, NS and HS. Adverse effects of
rhDNase suggest this should not be administered in non-CF
bronchiectasis.