Oral and Inhaled Corticosteroid Use and the Risk of Recurrent Pulmonary Embolism

The use of oral and inhaled corticosteroids is associated with a variety of adverse effects.  However, they are an accepted necessity in in the treatment of COPD, and provide necessary expansion of airways to help patients struggling to breath.  Many COPD patients suffer pulmonary embolism, and a significant proportion of these patients experience recurrent pulmonary embolism.  There is serious concern that the use of inhaled or oral corticosteroids may increase the lifetime risk of recurrent pulmonary embolism, and raise treatment related morbidity and mortality.  A recent study published in Thrombosis Research attempted to investigate a potential link between current or past use of corticosteroids and the incidence of recurrent pulmonary embolism among patients.

The researchers conducted a nested case-control study that looked at adult patients with a previous PE treated with Vitamin K antagonists.  The study analyzed 1414 PE patients, of which 384 were also later diagnosed with recurrent PE.  The study found that inhaled corticosteroid use only slightly associated with increased risk of recurrent PE, however oral medications did show increased odds of the disease.  In particular, current users of oral formulations were at increased risk (3.74 O.R., 95% CI 2.04-6.87), while past users were actually at a reduced risk (0.46 95% CI 0.28-0.74) compared to patients who never received corticosteroid therapy.  The researchers did admit the study design did not all them to discern whether the risk could be attributed solely on the medications or the underlying inflammatory disease as well.  However, they site evidence that corticosteroid medications show increased blood coagulation factors in healthy volunteers.

Inhaled and oral corticosteroids continue to be a mainstay of treatment for patients with chronic inflammatory diseases like COPD.  However, these disease states put the patients at increased risk for PE, and it would appear that the medications increase the risk of recurrent PE in the same patients.  Given the substantial risk of PE morbidity and mortality, these findings could have severe clinical impact for medication therapy of COPD and other inflammatory diseases of the pulmonary system.  As pharmacists, this association could have a large impact on the therapy management in future patients.  What steps should be taken to refine counseling points on corticosteroids, particularly in oral formulations?  Should the risk be assessed and accepted or denied on a patient-by-patient basis, or is there a better solution to the issue?

Article Link

Sneeboer, Marlous. Hutten, Barbara. Majoor, Christof. Bel, Elizabeth.  Oral and Inhaled Corticosteroid Use and the Risk of Pulmonary Embolism.  Thromres (2016); 140: 46-50.

Endocrine Effects of Inhaled Corticosteroids in Children

The effectiveness of inhaled corticosteroids (ICSs) in treating various chronic respiratory illnesses, such as allergic rhinitis, asthma, and cystic fibrosis, has increased over the years. Newer devices and formulations of the inhaled drug have reduced local adverse effects, but the improved delivery of the drug to the lungs increases systemic absorption and consequently can present a new set of adverse effects. This review article reviews the range and severity of these effects in children and sites various recommendations for prescribers and health care professionals when giving such inhalants.

The most serious potential adverse effect that can result from inhaled corticosteroids is adrenal insufficiency. Long term use of ICSs in children can lead to bone mineralization, DM1 and DM2, obesity, and this insufficiency, or suppression of the hypothalamic-pituitary-adrenal. The authors reviewed a case study on a 7-year-old female that presented with a new onset seizure due to adrenal insufficiency after using an inhalant regimen to treat her asthma. They concluded that clinical effectiveness of inhalants and systemic absorption have a strong positive correlation that can only be partially explained by the device and formulation modifications of the drug. Conclusions and research were also done on the drugs’ effects on bone mineral density, which were found to be mild, and suppression of linear growth, which were found to be slightly correlated. The article presents that generally, inhaled corticosteroids are safe and effective drugs, but life-threatening endocrine effects can occur even with normal doses. It is suggested that reducing systemic adverse effects could require increasing drug protein binding and rapid clearance time, as well as decreased lipophilicity.

This article brings to light something that most parents of children using inhaled corticosteroids are unaware about. I think that using education in this case is probably the best way to avoid this problem, seeing as inhaled corticosteroids are the most effective treatment in reducing respiratory distress. Pharmacists caring for children that routinely use ICSs could really play a major part in watching for adverse endocrine effects by providing correct dosing schedules and learning about how often patients use their inhalers.

JAMA Pediatr. 2016;170(2):163-170. Link to Article