Bronchodilators and cystic fibrosis


	back

Bronchodilators

The Leeds Method of Management. April, 2008. Bronchodilators [online]. Leeds Regional Adult and Paediatric Cystic Fibrosis Units, St James's University Hospital, Leeds, UK. Available from http://www.cysticfibrosismedicine.com

Introduction

Bronchodilators may improve respiratory function in patients with CF (Conway & Watson, 1997; Ziebach et al, 2001). Approximately 50% of patients have some degree of bronchial lability (asthma) which will improve with a bronchodilator (Eggleston et al, 1988). Improving airway patency before physiotherapy may help in the clearance of secretions from the chest. Bronchodilators may be given before physiotherapy for this reason. Bronchodilators are free from serious side effects although mild tremor may develop in some patients and some medications may lead to paroxysmal bronchoconstriction.

Practicalities of treatment

All patients should be tested regularly with a bronchodilator (e.g. at the annual assessment) to determine if bronchial lability is present. The response varies from time to time in individual patients and appears more marked when infection is more active, reducing as a respiratory exacerbation responds to antibiotic treatment. Bronchodilator responsiveness is generally assessed by measuring lung function before and after bronchodilator inhalation. An increase of baseline FEV1 of at least 10% is considered significant (Halfhide et al, 2005). A chart of the twice daily peak expiratory flow rates may be a useful method of measuring the severity of bronchial lability (difference between the best and the worst values) and monitoring the effects of any new treatment.

Bronchodilators may be administered via nebulisation, aerosol or dry powder inhaler. The patient should be assessed for the most appropriate device for their individual requirements. Nebulisation can provide larger doses but is more time consuming and requires more equipment. Inhalers are easier to carry around to use as needed. The type of inhaler provided will depend on the medication prescribed, the patients maximal inspiratory flow rate, any co-morbidity, and preference. Dry powder inhalers require a higher inspiratory flow rate and a breath hold to be achieved while metered dose inhalers require co-ordination and hand mobility and strength. Spacers improve deposition and remove the need for breath holds and co-ordination but are more bulky to carry.

Available bronchodilator preparations

Short acting

Nebulised ß2-agonists are the most commonly prescribed agents for patients with CF but studies showing benefit are underpowered (Yankaskas et al, 2004). There are large variations in the dose and delivery of ß-adrenergic agonists which continue even 24 years after Stainfoth’s and colleagues’ publication (Stainforth et al, 1983). The British Thoracic Society (BTS) guidelines for nebuliser therapy highlight the lack of research in patients with CF. Physicians see the use of bronchodilators as ‘good practice’ but there is little information on efficacy or optimal dosage (BTS guidelines, 1997). Since these guidelines were published little has changed. In 2005 the Cochrane Collaboration stated that ‘despite the wide-scale and often long-term use of bronchodilators in CF, there is little objective evidence regarding their efficacy’ (Halfide et al, 2005).

In a study carried out at the Leeds Adult CF Unit in 2006, 15 out of 83 patients (18.1%) showed a significant response to reversibility testing with nebulised salbutamol during their annual assessment (Hughes et al, 2006). The main predictive factor for a positive response was lower pre-existing lung function. There are no trials looking at the effect of terbutaline or fenoterol compared with placebo within the CF population (Halfhide et al, 2005).

Long acting

Salmeterol (Serevent®) is a long acting ß2-agonist which has been shown to improve respiratory function in two-thirds of adult patients with bronchial lability (Bargon et al, 1996). High doses of salmeterol can improve lung function in hospitalised patients (Hordvik et al, 1999), reduce the frequency of antibiotic treatments and improve sleep quality in outpatients (Hordvik et al, 2002). Those showing an improvement in daytime lung function after salbutamol therapy may benefit from salmeterol administration before sleep. Statistically significant increases in mean arterial oxyhaemoglobin saturation and respiratory function on awakening are documented (Salvatore & D’Andria, 2002). Salmeterol has a slow onset of action and is therefore not suitable for short term relief of bronchoconstriction.

Eformoterol fumarate (Oxis®) may be used as an alternative to salmeterol although there are no studies of the effects of this medication within the CF population (Halfhide et al, 2005). An advantage of eformoterol is the speed of onset of action which is similar to salbutamol. Eformoterol may be used for short-term symptomatic relief as well as for long term maintenance treatment.

Antimuscarinic agents

Short-acting

Ipratropium bromide (Atrovent®) is generally added to other bronchodilator treatment rather than being prescribed in isolation as the onset of action is slower than that of selective ß2-agonists. Small scale studies have reported improvements in respiratory function with ipratropium in some patients (Wiebicke et al, 1990; Avital et al, 1992; Sanchez et al, 1993; Ziebach et al, 2001). These studies were underpowered and the response reported was variable between patients. Acute angle glaucoma is reported with nebulised ipratropium (British National Formulary, 2007), which should always be nebulised using a mouthpiece rather than a mask.

Long-acting

Tiotropium (Spiriva®) is a long-acting antimuscarinic bronchodilator which reduces exacerbations and rehospitalisations, and improves quality of life and respiratory function in patients with COPD (Barr et al, 2005). There are no studies of tiotropium in patients with CF.

Compound bronchodilator preparations

Combivent® (ipratropium bromide & salbutamol) and Duovent® (ipratropium bromide and fenoterol hydrobromide) are available. Decreasing the number of devices required to take prescribed treatment may improve patient adherence with medication. However, the flexibility of dose adjustment of each component of the bronchodilator is lost. There is no evidence to support or refute the use of compound preparations in this patient group.

Bronchodilators and nebulised antibiotics

Patients should be assessed before and after a test dose of a nebulised antibiotic. In children chest auscultation and, where possible, respiratory function tests are performed. In adults pre and post respiratory function tests are performed. Some patients will develop bronchospasm and may benefit from bronchodilator inhalation given before the antibiotic (Dodd et al, 1997; Cunningham et al, 2001; Alothman et al, 2002).

Key points

• Approximately 50% of patients have some degree of bronchial lability which will improve with a bronchodilator

• Improving airway patency before physiotherapy may help in the clearance of secretions from the chest

• Some patients will develop bronchospasm following nebulised antibiotics and may benefit from the addition of a bronchodilator

References

Alothman GA, Alsaadi MM, Ho BL, et al. Evaluation of bronchial constriction in children with cystic fibrosis after inhaling two different preparations of tobramycin. Chest 2002; 122: 930-934. [PubMed]

Avital A, Sanchez I, Chernick V. Efficacy of salbutamol and ipratropium bromide in decreasing bronchial hyperreactivity in children with cystic fibrosis. Pediatr Pulmonol 1992; 13: 34-37. [PubMed]

Bargon I, Viel K, Wiewrodt R, et al. Efficacy of nebulised salmeterol in the treatment of adult patients with cystic fibrosis. Israel J Med Sci 1996; 32 Suppl; S221.

Barr RG, Bourbeau J, Camargo CA, et al. Tiotropium for stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2005; 2: CD002876. [PubMed]

British Thoracic Society (BTS) guidelines. Nebuliser treatment best practice. Thorax 1997; 52: 1-104. [PubMed] [Links]

Conway SP, Watson A. Nebulised bronchodilators, corticosteroids and rhDnase in adult patients with cystic fibrosis. Thorax 1997; 52: 564-569. [PubMed]

Cunningham S, Prasad A, Collye L, et al. Bronchoconstriction following nebulised colistin in cystic fibrosis. Arch Dis Child 2001; 84: 432-433. [PubMed]

Dodd ME, Abbott J, Maddison J, et al. The effect of the tonicity of nebulised colistin on chest tightness and pulmonary function in adults with cystic fibrosis. Thorax 1997; 52: 656-658. [PubMed]

Eggleston PA, Rosenstein BJ, Stackhouse CM, et al. Airway hyperreactivity in cystic fibrosis. Clinical correlates and possible effects on the course of the disease. Chest 1988; 94: 360-365. [PubMed]

Halfhide C, Evans HJ, Couriel J. Inhaled bronchodilators for cystic fibrosis. Cochrane Database of Syst Rev 2005; 4: CD003428. [PubMed]

Hordvik NL, Sammut PH, Judy CG, et al. Effects of standard and high doses of salmeterol on lung function of hospitalised patients with cystic fibrosis. Pediatr Pulmonol 1999; 27: 43-53. [PubMed]

Hordvik NL, Sammut PH, Judy CG, et al. Effectiveness and tolerability of high-dose salmeterol in cystic fibrosis. Pediatr Pulmonol 2002; 34: 287-296. [PubMed]

Hughes T, Clifton I, Etherington C, et al. A retrospective study to assess the response to nebulised salbutamol during a period of stability in adult patients with cystic fibrosis J Cyst Fibros 2006; 5(Suppl 1): S44.

Salvatore D, D’Andria M. Effects of salmeterol on arterial oxyhemoglobin saturations in patients with cystic fibrosis. Pediatr Pulmonol 2002; 34: 11-15. [PubMed]

Sanchez I, De Koster J, Holbrow J, et al. The effect of high doses of inhaled salbutamol and ipratropium bromide in patients with stable cystic fibrosis. Chest 1993; 104: 842-846. [PubMed]

Stainforth JN, Lewis RA, Tattersfield AE. Dosage and delivery of nebulised beta agonists in hospital. Thorax 1983; 38: 751-754. [PubMed]

Wiebicke W, Poynter A, Montgomery M, et al. The effect of ipratropium bromide on lung function in patients with Cystic Fibrosis. Article in German. Pneumologie 1990; 44(Suppl 1): 277-278. [PubMed]

Yankaskas JR, Marshall BC, Sufian B, et al. Cystic fibrosis adult care: consensus conference report. Chest 2004; 125: 1S-39S. [PubMed]

Ziebach R, Pietsch-Breitfeld B, Bichler M. Bronchodilatory effects of salbutamol, ipratropium bromide and their combination: double blind placebo controlled crossover study in cystic fibrosis. Pediatr Pulmonol 2001; 31: 431-435. [PubMed]