Asthma is a common condition that affects the airways, the small tubes that carry air in and out of the lungs. People can have underlying inflammation in their lungs and sticky mucus or phlegm may build up, which can narrow the airways. When a person with asthma comes into contact with an irritant (an asthma trigger), the muscles around the walls of the airways tighten, the airways become narrower, and the lining of the airways becomes inflamed and starts to swell. This leads to the symptoms of asthma, which are wheezing, coughing and difficulty in breathing. There is no cure for asthma; however, there are medications that allow most people to control their asthma so they can get on with daily life. People with asthma are generally advised to take inhaled corticosteroids to combat the underlying inflammation in their lungs. If asthma is still not controlled, current clinical guidelines recommend the introduction of an additional medication to help. One type of additional medication is the long-acting beta₂-agonists, such as formoterol  and salmeterol, which work by reversing the narrowing of the airways that occurs during an asthma attack. These drugs, taken by inhaler, are known to improve lung function, symptoms, quality of life and to reduce the number of asthma attacks. However, the evidence for the usefulness of long-acting beta₂-agonists is more limited in children than adults, and there are concerns about the safety of these drugs in both adults and children. We did this overview to take a closer look at the safety of formoterol or salmeterol, either alone or given in combination with corticosteroid therapy, in children with asthma. 

We looked at previous Cochrane reviews on long-acting beta₂-agonists and also searched for additional trials on long-acting beta₂-agonists in children. We found a total of 21 trials involving 7318 children that provided information on the safety of formoterol or salmeterol given alone or combined with corticosteroids. We also found one trial on 156 children which directly compared formoterol to salmeterol.

There were more non-fatal serious adverse events in children taking formoterol or salmeterol compared to those on placebo; for every 1000 children treated with formoterol or salmeterol over six months, 21 extra children suffered a non-fatal event in comparison with placebo. There was a smaller and non-significant increase in serious adverse events in children on formoterol or salmeterol and corticosteroids compared to corticosteroids alone: for every 1000 children treated with combination therapy over three months, three extra children suffered a non-fatal event in comparison with corticosteroids alone. This number illustrates the average difference between combination therapy and corticosteroids. Our analyses showed that in fact the true answer could be between 1 fewer and 12 more children who would experience a non-fatal event. 

We did not have enough numbers from the small trial comparing formoterol to salmeterol, or from information in the other trials, to tell whether one long-acting beta₂-agonist treatment is safer than the other. There was only one death across all the trials, so we did not have enough information to tell whether formoterol or salmeterol increases the risk of death.