title: Mucoactive agents for chronic, non-cystic fibrosis lung disease: A systematic review and meta-analysis.
abstract: 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.
authors.affiliation: Department of Physiotherapy, Alfred Health, Melbourne, Victoria, Australia.|Department of Rehabilitation, Nutrition and Sport, La Trobe University, Melbourne, Victoria, Australia.
authors.forename: Benjamin J
authors.identifier: 0000-0002-5572-1644
authors.initials: BJ
authors.lastname: Tarrant
authors.affiliation: Department of Physiotherapy, Alfred Health, Melbourne, Victoria, Australia.
authors.forename: Caitlin
authors.initials: C
authors.lastname: Le Maitre
authors.affiliation: Ian Potter Library, Alfred Health, Melbourne, Victoria, Australia.
authors.forename: Lorena
authors.identifier: 0000-0001-9884-5463
authors.initials: L
authors.lastname: Romero
authors.affiliation: Department of Physiotherapy, Alfred Health, Melbourne, Victoria, Australia.
authors.forename: Ranjana
authors.initials: R
authors.lastname: Steward
authors.affiliation: Department of Physiotherapy, Alfred Health, Melbourne, Victoria, Australia.|Department of Allergy, Immunology and Respiratory Medicine (AIRmed), Monash University, Melbourne, Victoria, Australia.
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Button
authors.affiliation: Department of Allergy, Immunology and Respiratory Medicine (AIRmed), Monash University, Melbourne, Victoria, Australia.|Department of Allergy, Immunology and Respiratory Medicine, Alfred Health, Melbourne, Victoria, Australia.
authors.forename: Bruce R
authors.identifier: 0000-0002-5885-0652
authors.initials: BR
authors.lastname: Thompson
authors.affiliation: Department of Physiotherapy, Alfred Health, Melbourne, Victoria, Australia.|Department of Rehabilitation, Nutrition and Sport, La Trobe University, Melbourne, Victoria, Australia.
authors.forename: Anne E
authors.identifier: 0000-0003-2061-845X
authors.initials: AE
authors.lastname: Holland
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology / Q000627:therapeutic use*; D000280:Administration, Inhalation; D001987:Bronchiectasis / Q000188:drug therapy* / Q000503:physiopathology; D002908:Chronic Disease; D003850:Deoxyribonuclease I / Q000494:pharmacology / Q000627:therapeutic use*; D005100:Expectorants / Q000494:pharmacology / Q000627:therapeutic use*; D005541:Forced Expiratory Volume; D006801:Humans; D008171:Lung Diseases / Q000188:drug therapy* / Q000503:physiopathology; D008353:Mannitol / Q000494:pharmacology / Q000627:therapeutic use*; D015080:Mesna / Q000627:therapeutic use; D009079:Mucociliary Clearance / Q000187:drug effects; D011788:Quality of Life; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D012462:Saline Solution, Hypertonic / Q000494:pharmacology / Q000627:therapeutic use*; D000067251:Symptom Flare Up; D014797:Vital Capacity
chemical_list: D005100:Expectorants; D011994:Recombinant Proteins; D012462:Saline Solution, Hypertonic; D008353:Mannitol; D003850:Deoxyribonuclease I; C568813:dornase alfa; D015080:Mesna; D000111:Acetylcysteine
keywords: expectorants; humans; lung diseases; respiratory function tests; sputum