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in preventing the exacerbation from occurring, according to the results of two trials in adults and children.
Presented at the joint congress of the American Academy of Allergy, Asthma, and Immunology and the World Asthma Organization and simultaneously published in the March 3 online edition of the New England Journal of Medicine, one study explored the effect of quadrupling the inhaled glucocorticoid dose in adults and adolescents with asthma, while the other looked at quintupling the dose in children.
At 1 year, there was a significantly lower incidence of severe asthma exacerbations in the group who used the higher dose of inhaled glucocorticoids (45% vs. 52%; hazard ratio, 0.80; P = .001) after adjusting for age, sex, and peak flow measures at randomization.
Researchers also saw a lower percentage of participants using systemic glucocorticoids in the quadruple-dose group compared with the normal-dose group (33% vs. 40%), and the quadruple-dose group also showed a 14% lower incidence of unscheduled health care consultations.
At the end of the 12-month follow-up, the estimated mean total dose of inhaled glucocorticoids was 385 mg in the quadruple-dose group and 328 mg in the normal-dose group.
The most common serious adverse event was hospitalization for asthma, which occurred three times in the quadruple-dose group and 18 times in the normal-dose group. However the incidence of oral candidiasis and dysphonia – both potentially treatment related – was significantly higher in the quadruple-dose group (36 events vs. 9 events).
Overall, the number needed to treat with the quadruple dose to prevent one severe asthma exacerbation was 15.
“Given the potential benefit with respect to preventing exacerbations and in view of the toxic effects of inhaled glucocorticoids and the biases that may have been introduced by the absence of blinding, individual practitioners, patients, and guideline committees will need to consider whether the magnitude of the reduction achieved is clinically meaningful,” wrote Tricia McKeever, PhD, from the department of epidemiology and public health at the University of Nottingham (United Kingdom) and her coauthors.
The second study, which was double blinded, investigated whether quintupling the dose of inhaled glucocorticoids might avoid exacerbations in children. They randomized 254 children who had mild-moderate persistent asthma and had had at least one exacerbation treated with systemic glucocorticoids in the previous year to manage “yellow zone” early warning signs with either normal dose or five times their usual dose of inhaled glucocorticoids.
The rate of severe asthma exacerbations did not differ significantly between the quintuple-dose and normal-dose groups at the 1-year follow-up (0.48 vs. 0.37; P = 0.3), nor did the time to the first severe exacerbation or the rate of emergency department or urgent care visits.
The four hospitalizations for asthma all occurred in the high-dose group. However, there was a lower growth rate seen in children in the high-dose group than in the low-dose group (5.43 cm/yr vs. 5.65 cm/yr; P = .06). There were no significant differences between the two groups in other adverse events.
However, Daniel J. Jackson, MD, and his coauthors noted that there were fewer yellow zone episodes and fewer exacerbations in both groups than they had anticipated.
“It is important to recognize that our findings are specific to school-age children with mild-to-moderate persistent asthma regularly treated with daily low-dose inhaled glucocorticoids (with good adherence),” wrote Dr. Jackson from the department of pediatrics at the University of Wisconsin–Madison and his coauthors.
The first study was supported by the National Institute for Health Research. Six authors declared grants, personal fees and other funding and support from the pharmaceutical industry outside the submitted work.
The second study was supported by the National Heart, Lung, and Blood Institute. Fifteen authors declared grants, personal fees and other funding from the pharmaceutical industry, as well as other private industry, outside the submitted work. Several also declared grants from organizations including the National Institutes of Health.
SOURCE: McKeeve T et al. N Engl J Med. 2018 Mar 3. doi: 10.1056/NEJMoa1714257; Jackson DJ et al. N Engl J Med. 2018 Mar 3. doi: 10.1056/NEJM0a1710988.
These two trials address the important question of whether substantial escalation of regularly used inhaled glucocorticoids prevents exacerbations if started at the first sign of deterioration, as this so-called yellow zone has long been thought the perfect time to initiate more aggressive care. However glucocorticoids have serious side effects, and there is some preclinical evidence that they may enhance viral replication
One trial shows that escalating dose in this yellow zone does not prevent exacerbations in children with the early signs of asthma instability. The second trial is more complex and more controversial, as the open-label design may have biased the outcome, and the degree of benefit is debatable.
Together, these studies suggest that high doses of inhaled glucocorticoids either do not prevent exacerbations or only do so in a small subgroup of patients with as-yet-undefined baseline and exacerbation characteristics.
Philip G. Bardin, PhD, is from the Monash Lung and Sleep Unit at the Monash University Medical Centre in Melbourne, Australia. These comments are taken from an accompanying editorial (N Engl J Med. 2018 Mar 3. doi: 10.1056/NEJMe1800152). Dr. Bardin reported personal fees from GlaxoSmithKline outside the submitted work.
These two trials address the important question of whether substantial escalation of regularly used inhaled glucocorticoids prevents exacerbations if started at the first sign of deterioration, as this so-called yellow zone has long been thought the perfect time to initiate more aggressive care. However glucocorticoids have serious side effects, and there is some preclinical evidence that they may enhance viral replication
One trial shows that escalating dose in this yellow zone does not prevent exacerbations in children with the early signs of asthma instability. The second trial is more complex and more controversial, as the open-label design may have biased the outcome, and the degree of benefit is debatable.
Together, these studies suggest that high doses of inhaled glucocorticoids either do not prevent exacerbations or only do so in a small subgroup of patients with as-yet-undefined baseline and exacerbation characteristics.
Philip G. Bardin, PhD, is from the Monash Lung and Sleep Unit at the Monash University Medical Centre in Melbourne, Australia. These comments are taken from an accompanying editorial (N Engl J Med. 2018 Mar 3. doi: 10.1056/NEJMe1800152). Dr. Bardin reported personal fees from GlaxoSmithKline outside the submitted work.
These two trials address the important question of whether substantial escalation of regularly used inhaled glucocorticoids prevents exacerbations if started at the first sign of deterioration, as this so-called yellow zone has long been thought the perfect time to initiate more aggressive care. However glucocorticoids have serious side effects, and there is some preclinical evidence that they may enhance viral replication
One trial shows that escalating dose in this yellow zone does not prevent exacerbations in children with the early signs of asthma instability. The second trial is more complex and more controversial, as the open-label design may have biased the outcome, and the degree of benefit is debatable.
Together, these studies suggest that high doses of inhaled glucocorticoids either do not prevent exacerbations or only do so in a small subgroup of patients with as-yet-undefined baseline and exacerbation characteristics.
Philip G. Bardin, PhD, is from the Monash Lung and Sleep Unit at the Monash University Medical Centre in Melbourne, Australia. These comments are taken from an accompanying editorial (N Engl J Med. 2018 Mar 3. doi: 10.1056/NEJMe1800152). Dr. Bardin reported personal fees from GlaxoSmithKline outside the submitted work.
in preventing the exacerbation from occurring, according to the results of two trials in adults and children.
Presented at the joint congress of the American Academy of Allergy, Asthma, and Immunology and the World Asthma Organization and simultaneously published in the March 3 online edition of the New England Journal of Medicine, one study explored the effect of quadrupling the inhaled glucocorticoid dose in adults and adolescents with asthma, while the other looked at quintupling the dose in children.
At 1 year, there was a significantly lower incidence of severe asthma exacerbations in the group who used the higher dose of inhaled glucocorticoids (45% vs. 52%; hazard ratio, 0.80; P = .001) after adjusting for age, sex, and peak flow measures at randomization.
Researchers also saw a lower percentage of participants using systemic glucocorticoids in the quadruple-dose group compared with the normal-dose group (33% vs. 40%), and the quadruple-dose group also showed a 14% lower incidence of unscheduled health care consultations.
At the end of the 12-month follow-up, the estimated mean total dose of inhaled glucocorticoids was 385 mg in the quadruple-dose group and 328 mg in the normal-dose group.
The most common serious adverse event was hospitalization for asthma, which occurred three times in the quadruple-dose group and 18 times in the normal-dose group. However the incidence of oral candidiasis and dysphonia – both potentially treatment related – was significantly higher in the quadruple-dose group (36 events vs. 9 events).
Overall, the number needed to treat with the quadruple dose to prevent one severe asthma exacerbation was 15.
“Given the potential benefit with respect to preventing exacerbations and in view of the toxic effects of inhaled glucocorticoids and the biases that may have been introduced by the absence of blinding, individual practitioners, patients, and guideline committees will need to consider whether the magnitude of the reduction achieved is clinically meaningful,” wrote Tricia McKeever, PhD, from the department of epidemiology and public health at the University of Nottingham (United Kingdom) and her coauthors.
The second study, which was double blinded, investigated whether quintupling the dose of inhaled glucocorticoids might avoid exacerbations in children. They randomized 254 children who had mild-moderate persistent asthma and had had at least one exacerbation treated with systemic glucocorticoids in the previous year to manage “yellow zone” early warning signs with either normal dose or five times their usual dose of inhaled glucocorticoids.
The rate of severe asthma exacerbations did not differ significantly between the quintuple-dose and normal-dose groups at the 1-year follow-up (0.48 vs. 0.37; P = 0.3), nor did the time to the first severe exacerbation or the rate of emergency department or urgent care visits.
The four hospitalizations for asthma all occurred in the high-dose group. However, there was a lower growth rate seen in children in the high-dose group than in the low-dose group (5.43 cm/yr vs. 5.65 cm/yr; P = .06). There were no significant differences between the two groups in other adverse events.
However, Daniel J. Jackson, MD, and his coauthors noted that there were fewer yellow zone episodes and fewer exacerbations in both groups than they had anticipated.
“It is important to recognize that our findings are specific to school-age children with mild-to-moderate persistent asthma regularly treated with daily low-dose inhaled glucocorticoids (with good adherence),” wrote Dr. Jackson from the department of pediatrics at the University of Wisconsin–Madison and his coauthors.
The first study was supported by the National Institute for Health Research. Six authors declared grants, personal fees and other funding and support from the pharmaceutical industry outside the submitted work.
The second study was supported by the National Heart, Lung, and Blood Institute. Fifteen authors declared grants, personal fees and other funding from the pharmaceutical industry, as well as other private industry, outside the submitted work. Several also declared grants from organizations including the National Institutes of Health.
SOURCE: McKeeve T et al. N Engl J Med. 2018 Mar 3. doi: 10.1056/NEJMoa1714257; Jackson DJ et al. N Engl J Med. 2018 Mar 3. doi: 10.1056/NEJM0a1710988.
in preventing the exacerbation from occurring, according to the results of two trials in adults and children.
Presented at the joint congress of the American Academy of Allergy, Asthma, and Immunology and the World Asthma Organization and simultaneously published in the March 3 online edition of the New England Journal of Medicine, one study explored the effect of quadrupling the inhaled glucocorticoid dose in adults and adolescents with asthma, while the other looked at quintupling the dose in children.
At 1 year, there was a significantly lower incidence of severe asthma exacerbations in the group who used the higher dose of inhaled glucocorticoids (45% vs. 52%; hazard ratio, 0.80; P = .001) after adjusting for age, sex, and peak flow measures at randomization.
Researchers also saw a lower percentage of participants using systemic glucocorticoids in the quadruple-dose group compared with the normal-dose group (33% vs. 40%), and the quadruple-dose group also showed a 14% lower incidence of unscheduled health care consultations.
At the end of the 12-month follow-up, the estimated mean total dose of inhaled glucocorticoids was 385 mg in the quadruple-dose group and 328 mg in the normal-dose group.
The most common serious adverse event was hospitalization for asthma, which occurred three times in the quadruple-dose group and 18 times in the normal-dose group. However the incidence of oral candidiasis and dysphonia – both potentially treatment related – was significantly higher in the quadruple-dose group (36 events vs. 9 events).
Overall, the number needed to treat with the quadruple dose to prevent one severe asthma exacerbation was 15.
“Given the potential benefit with respect to preventing exacerbations and in view of the toxic effects of inhaled glucocorticoids and the biases that may have been introduced by the absence of blinding, individual practitioners, patients, and guideline committees will need to consider whether the magnitude of the reduction achieved is clinically meaningful,” wrote Tricia McKeever, PhD, from the department of epidemiology and public health at the University of Nottingham (United Kingdom) and her coauthors.
The second study, which was double blinded, investigated whether quintupling the dose of inhaled glucocorticoids might avoid exacerbations in children. They randomized 254 children who had mild-moderate persistent asthma and had had at least one exacerbation treated with systemic glucocorticoids in the previous year to manage “yellow zone” early warning signs with either normal dose or five times their usual dose of inhaled glucocorticoids.
The rate of severe asthma exacerbations did not differ significantly between the quintuple-dose and normal-dose groups at the 1-year follow-up (0.48 vs. 0.37; P = 0.3), nor did the time to the first severe exacerbation or the rate of emergency department or urgent care visits.
The four hospitalizations for asthma all occurred in the high-dose group. However, there was a lower growth rate seen in children in the high-dose group than in the low-dose group (5.43 cm/yr vs. 5.65 cm/yr; P = .06). There were no significant differences between the two groups in other adverse events.
However, Daniel J. Jackson, MD, and his coauthors noted that there were fewer yellow zone episodes and fewer exacerbations in both groups than they had anticipated.
“It is important to recognize that our findings are specific to school-age children with mild-to-moderate persistent asthma regularly treated with daily low-dose inhaled glucocorticoids (with good adherence),” wrote Dr. Jackson from the department of pediatrics at the University of Wisconsin–Madison and his coauthors.
The first study was supported by the National Institute for Health Research. Six authors declared grants, personal fees and other funding and support from the pharmaceutical industry outside the submitted work.
The second study was supported by the National Heart, Lung, and Blood Institute. Fifteen authors declared grants, personal fees and other funding from the pharmaceutical industry, as well as other private industry, outside the submitted work. Several also declared grants from organizations including the National Institutes of Health.
SOURCE: McKeeve T et al. N Engl J Med. 2018 Mar 3. doi: 10.1056/NEJMoa1714257; Jackson DJ et al. N Engl J Med. 2018 Mar 3. doi: 10.1056/NEJM0a1710988.
FROM AAAAI/WAO JOINT CONGRESS
Key clinical point: Escalating the dose of inhaled glucocorticoids at the first early warnings of an asthma exacerbation may not significantly reduce the likelihood of the exacerbation occurring.
Major finding: Fifteen individuals would need to quadruple their dose of inhaled glucocorticoids to avoid one asthma exacerbation.
Data source: Two randomized, controlled trials in 1,992 adolescents and adults and 254 children with asthma.
Disclosures: The first study was supported by the National Institute for Health Research. Six authors declared grants, personal fees, and other funding and support from the pharmaceutical industry outside the submitted work. The second study was supported by the National Heart, Lung, and Blood Institute. Fifteen authors declared grants, personal fees, and other funding from the pharmaceutical industry, as well as other private industry, outside the submitted work. Several also declared grants from organizations including the National Institutes of Health. No other conflicts of interest were declared.
Sources: McKeeve T et al. N Engl J Med. 2018 Mar 3. doi: 10.1056/NEJMoa1714257; Jackson DJ et al. N Engl J Med. 2018 Mar 3. doi: 10.1056/NEJM0a1710988.