Table 2 Treatments for prevention of exacerbations
Evidence type/studySummary of resultsNotes
Antimicrobial agents
    GeneralCochrane review,99 other systematic review93Generally beneficial (see text)Resistance and nebulised tobramycin poorly tolerated in some95
    Macrolides16Randomised non-placebo trial (n = 12) azithromycin for 6 months vs usual treatmentExacerbations significantly reduced in treatment arm compared with non-treatment arm (16 vs 5)
    Nebulised tobramycin94Double blind crossover RCT in 30 patients with P aeruginosa, 6 months eachNumber and days of admissions less in tobramycin arm but no difference in number of exacerbationsResistance and nebulised tobramycin poorly tolerated in some95
Anti-inflammatory agents
    Indomethacin100Cohort study, 25 mg three times daily for 28 daysReduction in peripheral neutrophil chemotaxis; no change in sputum albumin, elastase, myeloperoxidase or exacerbation
Mucolytics
    BromhexineCochrane review101Studies only in acute phaseNot universally available
    rhDNAseSystematic review101 102Increased exacerbation rate
Airway clearance
    Chest physiotherapyCochrane review103Two small trials on bronchiectasis, exacerbation rate not reported
    Inhaled hyperosmolar agentsCochrane review,104 additional RCT (non-blinded) using 7% HS105Neither study reported on exacerbation rates
Asthma therapies
    Inhaled corticosteroids (ICS)Cochrane review104 and double blind RCT using 500 μg fluticasone twice daily15Reduced exacerbation rate only seen in those with P aeruginosa infection.15 No significant effect of ICS in Cochrane review104Limited applicability in children-high dose ICS and children less likely to have P aeruginosa
    Oral corticosteroidsCochrane review106No RCTsNo data*
    AnticholinergicsCochrane review107No RCTsNo data*
    β2-agonistsCochrane review108 109No RCTsNo data*
    LTRACochrane review110No RCTsNo data*
Physical trainingCochrane review111 and RCT112 which was included in Cochrane as an abstract (data changed)No data on exacerbationPulmonary rehabilitation improves exercise tolerance, no additional advantage of simultaneous inspiratory muscle training
Environmental modificationNo data*Assumed beneficial (see text)
Oxygen (domiciliary)No data as sole therapy*Consider data from COPD showing benefit in survival but no effect on exacerbation113 114
SurgeryCochrane review115No RCTs. Cohort studies suggest beneficial in selected cases.1 Annual exacerbation rate reduced from 5.9 to 2.3Reduction in exacerbation rate similar in medically treated group.116 Adverse events of surgery115 117 118
VaccinesNo data*Advocated as vaccines prevent respiratory infections119
Ventilatory assistance
    NPPV†Retrospective case controlled study on NPPV with oxygen120Reduced hospitalisation rate, no difference in mortalityNo effect on survival
Retrospective study using NPPV with oxygen121Reduced hospitalisation days, improved QOLPaco2 stabilised after NIV but no change on Pao2
Model of care
    Nurse-ledCochrane review122No difference in infective exacerbations but increase in hospitalisations in nurse-led care compared with doctor-led careIncreased healthcare cost implications
Sputum surveillanceNo data*Suggestions that this should be done123 (frequency undefined)Chronic infection or colonisation prevalent (see text)
PsychosocialNo data*34% have depression, anxiety or both74

  • COPD, chronic obstructive pulmonary disease; HS, hypertonic saline; LTRA, leucotriene receptor antagonist; NPPV, non-invasive positive pressure ventilation; QOL, quality of life; RCT, randomised controlled trial.

  • *No other data specific to exacerbation based on single reviewer search on PubMed (March 2006).

  • †A review article suggested that non-invasive positive pressure ventilation is probably beneficial in reducing exacerbation days/episodes in those with chronic respiratory failure, although the data are scarce.113