In the JournalsPerspective

Steroid inhaler use increases risk for hard-to-treat lung infections

Older adults who were treated for asthma or COPD with inhaled corticosteroids were twice as likely to develop nontuberculous mycobacterial pulmonary disease infections than those who were not, according to findings published in the European Respiratory Journal.

Inhaled corticosteroids are the mainstay of asthma therapy and are often used in COPD,” Sarah K. Brode, MD, from the division of respirology at the University of Toronto, and colleagues wrote. “However, corticosteroids have inhibitory effects on innate and acquired immune function, and oral corticosteroids increase the risk of systemic infection. [Inhaled corticosteroids] are delivered directly to the lungs and therefore might increase susceptibility to local (lung) infections.”

Inhaled corticosteroid use increases the risk for pneumonia and tuberculosis, but there is little research on the potential risk for nontuberculous mycobacterial pulmonary disease (NTM-PD) infections, according to the researchers.

Brode and colleagues performed a population-based nested case-control study to determine the association between inhaled corticosteroid use and risk for NTM-PD and tuberculosis. The researchers analyzed linked laboratory and health administrative databases in Ontario, Canada, from 2001 through 2013, and identified 417,494 adults aged 66 years or older who were treated for obstructive lung disease, including asthma, COPD or asthma–COPD overlap syndrome. They used conditional logistic regression to compare inhaled corticosteroid use with nonuse among NTM-PD and tuberculosis cases and controls.

The cohort included 2,966 cases of NTM-PD and 327 cases of tuberculosis. Participants who were currently using inhaled corticosteroids were about twice as likely to develop NTM-PD, compared with nonusers (aOR = 1.86; 95% CI, 1.6-2.15), and the risk increased the longer they used steroid inhalers. Fluticasone was significantly associated with NTM-PD (aOR = 2.09; 95% CI, 1.8-2.43); however, budesonide was not (aOR = 1.19; 95% CI, 0.97-1.45). The researchers found a robust dose-response relationship between incident NTM-PD and cumulative inhaled corticosteroid exposure over 1 year. Current inhaled corticosteroid use and tuberculosis were not significantly associated (aOR = 1.43; 95% CI, 0.95-2.16).

“This research suggests that patients should discuss whether they need to use steroid inhalers with their clinicians, and whether the benefits outweigh the potential harms,” Brode said in a press release. “If they do need to use them, they should be on the lowest effective dose.

“Clinicians should carefully consider the potential benefits and harms of steroid inhalers in patients with asthma or COPD, especially those who have already had an infection of this type in the past.”

Infections with nontuberculous mycobacteria are not common, but they are serious and difficult to treat, Guy Brusselle, MD, science council chair of the European Respiratory Society, said in the release.

“We must consider the effects of steroid inhalers on the risk of these infections alongside their known benefits and side-effects,” he said. – by Alaina Tedesco

Disclosure: The authors report receiving a health research grant from the Physicians Services Incorporated Foundation.

 

Older adults who were treated for asthma or COPD with inhaled corticosteroids were twice as likely to develop nontuberculous mycobacterial pulmonary disease infections than those who were not, according to findings published in the European Respiratory Journal.

Inhaled corticosteroids are the mainstay of asthma therapy and are often used in COPD,” Sarah K. Brode, MD, from the division of respirology at the University of Toronto, and colleagues wrote. “However, corticosteroids have inhibitory effects on innate and acquired immune function, and oral corticosteroids increase the risk of systemic infection. [Inhaled corticosteroids] are delivered directly to the lungs and therefore might increase susceptibility to local (lung) infections.”

Inhaled corticosteroid use increases the risk for pneumonia and tuberculosis, but there is little research on the potential risk for nontuberculous mycobacterial pulmonary disease (NTM-PD) infections, according to the researchers.

Brode and colleagues performed a population-based nested case-control study to determine the association between inhaled corticosteroid use and risk for NTM-PD and tuberculosis. The researchers analyzed linked laboratory and health administrative databases in Ontario, Canada, from 2001 through 2013, and identified 417,494 adults aged 66 years or older who were treated for obstructive lung disease, including asthma, COPD or asthma–COPD overlap syndrome. They used conditional logistic regression to compare inhaled corticosteroid use with nonuse among NTM-PD and tuberculosis cases and controls.

The cohort included 2,966 cases of NTM-PD and 327 cases of tuberculosis. Participants who were currently using inhaled corticosteroids were about twice as likely to develop NTM-PD, compared with nonusers (aOR = 1.86; 95% CI, 1.6-2.15), and the risk increased the longer they used steroid inhalers. Fluticasone was significantly associated with NTM-PD (aOR = 2.09; 95% CI, 1.8-2.43); however, budesonide was not (aOR = 1.19; 95% CI, 0.97-1.45). The researchers found a robust dose-response relationship between incident NTM-PD and cumulative inhaled corticosteroid exposure over 1 year. Current inhaled corticosteroid use and tuberculosis were not significantly associated (aOR = 1.43; 95% CI, 0.95-2.16).

“This research suggests that patients should discuss whether they need to use steroid inhalers with their clinicians, and whether the benefits outweigh the potential harms,” Brode said in a press release. “If they do need to use them, they should be on the lowest effective dose.

“Clinicians should carefully consider the potential benefits and harms of steroid inhalers in patients with asthma or COPD, especially those who have already had an infection of this type in the past.”

Infections with nontuberculous mycobacteria are not common, but they are serious and difficult to treat, Guy Brusselle, MD, science council chair of the European Respiratory Society, said in the release.

“We must consider the effects of steroid inhalers on the risk of these infections alongside their known benefits and side-effects,” he said. – by Alaina Tedesco

Disclosure: The authors report receiving a health research grant from the Physicians Services Incorporated Foundation.

 

    Perspective
    Umur Hatipoglu

    Umur Hatipoglu

    Inhaled corticosteroids have been associated with increased risk for pneumonia in patients with COPD in epidemiological studies and randomized control trials. These pneumonia episodes may be consequential with hospitalizations and excess mortality. The risk for infection seems to increase with higher doses and with high potency formulations such as fluticasone.

    A recent publication in the European Respiratory Journal reports the results of a nested case-control study of more than 400,000 COPD patients, showing an increased risk for nontuberculous mycobacterial (NTM) infection associated with the use of inhaled corticosteroids. The findings from this study, which is the largest of its kind, extend the observations from previous smaller studies that pointed to this association.

    The risk appears to be low: 1,775 patients need to be treated for 1 year for one case of infection to occur. Nonetheless, it is of clinical importance since NTM infections are very difficult and cumbersome to treat. Patients with such infections need to take multiple medications for a duration of at least 12 months, typically up to 18 months.

    Prescription of inhaled corticosteroids, in aggregate, can reduce exacerbations and may impact quality of life favorably. However, inhaled corticosteroids may not be for everyone with COPD. Patients with asthma-COPD overlap syndrome, those who have severe exacerbations while on maximal bronchodilator therapy and those who have increased biomarkers such as high eosinophil count in blood may benefit more.

    Accumulating data on the adverse effects of inhaled corticosteroids should foster more rigorous consideration of risks and benefits, as well as use of the lowest effective dose possible when treating patients with COPD.

    • Umur Hatipoglu, MD
    • COPD Center at Cleveland Clinic

    Disclosures: Hatipoglu reports no relevant financial disclosures.