Little evidence exists to support the widespread use of bronchodilators to treat children and adults with cystic fibrosis.

“ Recurrent wheeze and breathlessness are common in people with cystic fibrosis, and bronchodilators are commonly prescribed, ” according to lead author Clare Halfhide, of the Royal Liverpool Children’s Hospital in England. “ Despite their wide-scale and often long-term use, there is limited objective evidence about their efficacy in cystic fibrosis.”

Cystic fibrosis is a genetically inherited disease afflicting the lungs and the digestive system, the result of both parents passing on an abnormal gene. It is chronic, progressive and ultimately fatal.

Cystic fibrosis causes the exocrine glands, which produce sweat and mucus, to produce thick mucus that clogs the lungs, causing chronic respiratory difficulties. The mucus also obstructs pancreatic ducts, preventing digestive enzymes from reaching the intestines. Consequently, people with cystic fibrosis have difficulties breathing, absorbing nutrients and eliminating non-digested food.

The Cochrane review included 14 trials randomized controlled trials comprising 257 participants with cystic fibrosis.

Several trials compared inhaled bronchodilator drugs to placebo by looking at two common measures of lung function. Forced expiratory volume, or FEV1, represents the volume of air that can be forced out in one second after taking a deep breath. Peak expiratory flow rate represents how fast a person can exhale air.

Improvements occurred primarily in a subgroup of the cystic fibrosis patients studied. These patients were known to have bronchial hyper-responsiveness — increased response of the airway to certain stimuli. Bronchial hyper-responsiveness and responsiveness to bronchodilator drugs are markers for asthma and can be also tested for in people with cystic fibrosis.

The reviewers found the following:

- Albuterol and Terbutaline, drugs classified as short-acting beta2-agonists, increased FEV1 and peak expiratory flow rate for patients known to have bronchial hyper-responsiveness; - Serevent ( Salmeterol ), classified as a long-acting beta2-agonist, also improved lung function for participants known to have bronchial hyper-responsiveness;
- Atrovent ( Ipratropium bromide ) showed no consistent effects on lung function in the trials under review.

The reviewers found no published trials that included inhaler-delivered Fenoterol, Formoterol or Tiotropium and wrote that use of those agents could not be supported.

The reviewers noted that the trials were too varied in design to allow for a pooling of data for a strict meta-analysis.
“ Before embarking on what might become lifelong bronchodilator therapy, bronchodilator responsiveness should be assessed by measuring lung function both before and after a test dose of salbutamol in a standardized way, looking for an increase in baseline FEV1 of at least 10 percent," the reviewers concluded.

John Colombo, at the University of Nebraska Medical Center, said, “ My bias is… that all cystic fibrosis patients deserve a trial of beta-agonist bronchodilator. This should be done in the pulmonary function test ( PFT ) laboratory, and, unless they develop significant adverse effects, short-acting beta-agonists should be considered as a trial for symptom relief, and possibly as an adjunct to airway clearance. A long-acting beta-agonist, of which Salmeterol is the only one studied to date, should be considered for a period of home use with assessment for changes in symptoms, antibiotic requirement, and PFT course.”

About 30,000 people in the United States are affected with cystic fibrosis, and 2,500 to 3,000 babies are born annually with the condition. It most commonly occurs in Caucasians of Northern European heredity.

Source: Cochrane Library, 2005


XagenaMedicine2005