Patients who have chronic obstructive pulmonary disease (COPD) are sometimes prescribed oral corticosteroids for a short time to treat acute episodes of worsening symptoms, also known as exacerbations. And medical research supports their use to prevent the patient from having to be re-hospitalized.
But the use of oral corticosteroids is also linked to a number of possible negative health consequences. For example, there is a good possibility that a COPD patient has other chronic conditions, such as osteoporosis, which is especially common among postmenopausal women. Oral corticosteroids can aggravate existing osteoporosis and increase the risk of fractures in those patients. For this reason many doctors, aware of the risks, tend to avoid prescribing long-term oral steroid therapy.
Inhaled corticosteroids and fracture risk
However, it is common for COPD patients to use inhaled corticosteroids (ICS) on a regular basis for maintenance, which has been deemed to be safe and effective. A study recently published in Chest aimed to substantiate the safety of using ICS in COPD patients.
In the study, researchers looked at a healthcare database (1990 to 2005) from Quebec, Canada, focusing specifically on patients who had a diagnosis of COPD. More than 240,000 people were followed.
Based on the data, researchers concluded that incidental use of ICS did not increase the risk of fractures while first using the therapy. But fracture risk did increase after four years of use.
The researchers also identified a dose threshold beyond which osteoporosis and fracture risk increased (1,000 mcg equivalent for fluticasone).There was no difference between men and women in this risk of fractures despite earlier suspicions.
A separate study showed a clear increase in the risk for vertebral fractures among subjects who used inhaled steroids. Vertebral fractures are more common among elderly patients who have osteoporosis, and it’s not commonly attributed to the use of inhaled corticosteroids (it’s assumed to be the natural progression of osteoporosis).
The significance of this finding is the time frame of the study (four years) and threshold dose, which is not a usual practice in the treatment of COPD.
Corticosteroids are anti-inflammatory drugs and there is clear evidence for their use in the management of asthma as a first-line therapy. The use in patients with stable COPD has not been clear.
The long-term effect of inhaled corticosteroids for the treatment of COPD was also studied in a meta-analysis of various research published between 1983 and 1996. It showed only a modest improvement in lung function in the first two years of use, and that finding was for high doses of the drug. It was precisely those dose levels that were shown to be linked to an increased rate of fractures.
What this means for the COPD patient
I recently wrote a column on the latest GOLD guidelines that were revised in January 2017. The new guidelines do not recommend ICS as an initial therapy. The recommendation is to combine an inhaled long-acting bronchodilator (LABA) and a long-acting muscarinic receptor antagonist (LAMA).
The addition of ICS is what is called “triple therapy.” The initiation of triple therapy is based on the clinical progression of COPD and how the condition presents itself in each patient.
What was also new in this updated set of guidelines is the identification of a unique form of COPD that includes elevated levels of eosinophils. Other studies have referred to this COPD patient subset as having “overlap syndrome” or having, in this case, both asthma and COPD.
Those patients show a demonstrable benefit from the use of ICS, though it’s not clear if that benefit is long term. And doctors need to take into account the benefits of the additional treatment versus the associated risk of fractures.
The bottom line
- The long-term use of inhaled corticosteroids should not be deemed to be safe, though it had previously been thought to be safe.
Inhaled corticosteroids should not be used as the first-line treatment for COPD but rather only added when double therapy results in progression of COPD symptoms.
There is a subset of COPD patients who have a more prominent inflammatory process and an elevated level of eosinophils. This subset of patients (who have overlap syndrome) will get the most benefit from inhaled corticosteroids.
More research on the use of ICS in the COPD patient is warranted.
Since a period of time (four years) and a dose threshold (1,000 mcg equivalent for fluticasone) has been identified, all efforts should be made to avoid exceeding those markers if inhaled corticosteroids are used.