Inhaled corticosteroids

Inhaled corticosteroids may increase risk of nontuberculous mycobacterial lung disease

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Inhaled corticosteroids ICS nontuberculous mycobacteria disease

Inhaled corticosteroids (ICS) were associated with an increased risk of nontuberculous mycobacteria pulmonary disease (NTM PD) in patients with asthma or chronic obstructive pulmonary disease (COPD) or both, compared with those who did not use ICS, according to a study presented at the recent American Thoracic Society (ATS) International Conference 2016 held in San Francisco, California, US.

ICS are commonly used for treating asthma and COPD, both of which are risk factors for NTM PD, according to the researchers. However, corticosteroids can inhibit immune function and have been associated with an increased risk of pneumonia.

The nested case-control study reviewed medical records of 417,494 patients (aged ≥66 years) with asthma or COPD or both in Ontario, Canada from 2001 to 2013. Among these patients, 2,964 NTM PD cases were identified based on results from microbiological tests. [ATS 2016, abstract 6187]

Current ICS users had an 84 percent higher risk of NTM PD compared with non-users (adjusted odds ratio [adjOR], 1.84, 95 percent confidence interval [CI], 1.59-2.13), while previous ICS users did not have any significant increase in risk of NTM PD.

Current ICS use remained significantly associated with risk of NTM PD even when only NTM PD treated with antimicrobial were included in the analysis (adjOR, 1.89, 95 percent CI, 1.32-2.71),

The increase in NTM PD risk associated with current ICS use was greatest among COPD patients, at 210 percent (adjOR, 2.10, 95 percent CI, 1.73-2.54), followed by patients with both asthma and COPD at 55 percent (adjOR, 1.55, 95 percent CI, 1.17-2.04). The association was not significant for asthma patients.

Additionally, the increase in NTM PD risk was significantly associated with ICS containing fluticasone (adjOR, 2.08, 95 percent CI, 1.79-2.42), but not budesonide (adjOR, 1.17, 95 percent CI, 0.96-1.43).

This difference might be attributed to the different potency of the two drugs, according to study principal investigator Dr. Sarah Brode, assistant professor of medicine at the University of Toronto in Toronto, Canada.

“Often people using fluticasone are using the highest dose, and the highest dose of fluticasone is a lot more potent than the highest dose of budesonide,” said Brode. “Although one cannot be certain, I don’t think it’s something innate in the molecules themselves.”

Further supporting their speculation, the researchers also found that the higher the cumulative dose of ICS used over 1 year, the greater the association was with incident NTM PD.

“Physicians should consider this risk when prescribing ICS, particularly for patients with COPD, who appear most vulnerable,” Brode said, advocating that ICS doses should be minimised for patients with COPD and asthma.

She also suggested that patients with mild to moderate COPD who had infrequent flare-ups could probably be spared from ICS.

“On the other hand, the benefits of ICS outweigh the risks for asthma patients, except for those with the mildest symptoms.”

Inhaled corticosteroids may increase risk of nontuberculous mycobacterial lung disease

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Inhaled corticosteroids ICS nontuberculous mycobacteria disease

Inhaled corticosteroids (ICS) were associated with an increased risk of nontuberculous mycobacteria pulmonary disease (NTM PD) in patients with asthma or chronic obstructive pulmonary disease (COPD) or both, compared with those who did not use ICS, according to a study presented at the recent American Thoracic Society (ATS) International Conference 2016 held in San Francisco, California, US.

ICS are commonly used for treating asthma and COPD, both of which are risk factors for NTM PD, according to the researchers. However, corticosteroids can inhibit immune function and have been associated with an increased risk of pneumonia.

The nested case-control study reviewed medical records of 417,494 patients (aged ≥66 years) with asthma or COPD or both in Ontario, Canada from 2001 to 2013. Among these patients, 2,964 NTM PD cases were identified based on results from microbiological tests. [ATS 2016, abstract 6187]

Current ICS users had an 84 percent higher risk of NTM PD compared with non-users (adjusted odds ratio [adjOR], 1.84, 95 percent confidence interval [CI], 1.59-2.13), while previous ICS users did not have any significant increase in risk of NTM PD.

Current ICS use remained significantly associated with risk of NTM PD even when only NTM PD treated with antimicrobial were included in the analysis (adjOR, 1.89, 95 percent CI, 1.32-2.71),

The increase in NTM PD risk associated with current ICS use was greatest among COPD patients, at 210 percent (adjOR, 2.10, 95 percent CI, 1.73-2.54), followed by patients with both asthma and COPD at 55 percent (adjOR, 1.55, 95 percent CI, 1.17-2.04). The association was not significant for asthma patients.

Additionally, the increase in NTM PD risk was significantly associated with ICS containing fluticasone (adjOR, 2.08, 95 percent CI, 1.79-2.42), but not budesonide (adjOR, 1.17, 95 percent CI, 0.96-1.43).

This difference might be attributed to the different potency of the two drugs, according to study principal investigator Dr. Sarah Brode, assistant professor of medicine at the University of Toronto in Toronto, Canada.

“Often people using fluticasone are using the highest dose, and the highest dose of fluticasone is a lot more potent than the highest dose of budesonide,” said Brode. “Although one cannot be certain, I don’t think it’s something innate in the molecules themselves.”

Further supporting their speculation, the researchers also found that the higher the cumulative dose of ICS used over 1 year, the greater the association was with incident NTM PD.

“Physicians should consider this risk when prescribing ICS, particularly for patients with COPD, who appear most vulnerable,” Brode said, advocating that ICS doses should be minimised for patients with COPD and asthma.

She also suggested that patients with mild to moderate COPD who had infrequent flare-ups could probably be spared from ICS.

“On the other hand, the benefits of ICS outweigh the risks for asthma patients, except for those with the mildest symptoms.”

Inhaled corticosteroids for neonatal BPD: The jury is still out

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Insight Post 10-14-15As neonatologists have been able save more babies that have born prematurely, the problem of bronchopulmonary dysplasia (BPD) has loomed larger. BPD occurs in preterm infants (born at less than 28 weeks of gestation) or in infants with extremely low birth weight (less than 1000 grams at birth). It stems from a variety of factors, including underdeveloped lung tissue, inflammation, and mechanical injury associated with ventilatory support (McEvoy et al, 2014). These factors lead to acute lung injury and subsequently, impaired repair and growth. BPD is associated with significant neonatal mortality and is in need of better therapy.

Randomized clinical trials have shown that systemic glucocorticoids can effectively decrease the incidence of BPD, but they may be associated with adverse effects such as intestinal perforation and cerebral palsy. To avoid the risks of systemic glucocorticoids, Bassler et al performed a multinational, randomized placebo-controlled trial, published in this week’s issue of NEJM, to test the effectiveness of budesonide, an inhaled glucocorticoid, to prevent BPD in preterm infants; the hope is that inhaled glucocorticoids will have local benefits in the lungs without getting into the systemic circulation. Of the 856 infants evaluated for the primary outcomes (development of BPD or death), the observed rate was 40.0% in the budesonide group and 46.3% in the placebo group (relative risk, stratified for gestational age, 0.86; 95% CI, 0.75-1.00; P=0.053). The composite outcome is driven primarily by a decrease in the risk of BPD (27.8% in the budesonide group vs. 38.0% in the placebo group, P=0.004) combined with a trend towards increased mortality in the budesonide group (16.9% vs. 13.6% in the placebo group, P=0.17). Thus, while inhaled corticosteroids may effectively prevent BPD, its ultimate benefit for neonates is unclear.

In an accompanying editorial, Barbara Schmidt, MD, points out that although the difference in mortality rate may be due to chance, the increased mortality could be due to pneumonia, which is a well-established risk with inhaled glucocorticoids in adults. Although no significant difference in the rate of sepsis or infection as a cause of death between the two groups was found, autopsies were only performed in 1/3 of the cases. These results, unfortunately, do not lead us towards any more clarity on how to prevent BPD, as it appears that inhaled glucocorticoids carry risks of their own.