Ted Bosworth

MADRID – A placebo-controlled trial has confirmed that amoxicillin/clavulanate is beneficial for resolution of acute exacerbations in nonsevere bronchiectasis while also demonstrating a greater relative effect than azithromycin, based on data presented at the annual congress of the European Respiratory Society.

“We now have robust data with which to support our guidelines,” reported Vikas Goyal, MD, of the Children’s Health Clinical Unit, University of Queensland, Brisbane, Australia.

The study addresses a knowledge gap. Antibiotics are already recommended by many guidelines for treatment of acute exacerbations in children with bronchiectasis, but Dr. Goyal said that no controlled trials have ever been performed in this age group to confirm superiority to placebo.

In this multicenter study, called BEST-1, 197 children with bronchiectasis were randomized at the start of an exacerbation to placebo, 45 mg/kg per day of amoxicillin/clavulanate, or 5 mg/kg per day of azithromycin. To maintain blinding, patients in the active treatment groups received a dummy for the opposite antibiotic while patients on placebo received dummies for both active agents.

For the primary outcome, 65% of children randomized to amoxicillin/clavulanate had resolution of their exacerbation by day 14 versus 61% of those randomized to azithromycin and 43% of those randomized to placebo. On the basis of relative risk for reaching this end point, the outcome was superior to placebo for amoxicillin/clavulanate (RR, 1.5; P = .015).

Although the relative risk for azithromycin (RR, 1.4; P = .042) was only slightly lower, it did not reach a prespecified level of significance set at P = .025. Dr. Goyal did report that the resolution rate at 14 days in the placebo group was “higher than expected.”

In this trial, 53% of the 154 children who were tested for respiratory viruses with nasal swabs on day 1 of the exacerbation were found to have respiratory viruses. Of these viruses, rhinovirus was the most common, according to Dr. Goyal, whose data were published just prior to his presentation (Lancet Respir Med. 2019;7:791-801).

The median durations of the exacerbations were 7 days, 8 days, and 10 days for those treated with amoxicillin/clavulanate, azithromycin, and placebo, respectively. The difference between amoxicillin/clavulanate and placebo, but not that between azithromycin and placebo, reached statistical significance, Dr. Goyal said.

There were no between group differences in the time to next exacerbation.

In discussing limitations of this study, Dr. Goyal pointed out that the optimal doses of amoxicillin/clavulanate or azithromycin have never been established for the treatment of exacerbations in children with bronchiectasis. He noted that some infectious disease specialists have advocated higher doses of both than those employed in this trial, but dose-ranging studies have never been conducted in this age group.

In this study, adverse events were less common on azithromycin than amoxicillin/clavulanate (21% vs. 30%), but none were severe, according to Dr. Goyal. He said treatment with azithromycin was associated with increased macrolide-resistant bacteria.

On the basis of these data, Dr. Goyal concluded that amoxicillin/clavulanate should remain, as already specified in some guidelines, the standard first-line therapy for nonsevere exacerbations in nonhospitalized children with bronchiectasis. He recommended reserving azithromycin as an alternative therapy.

Dr. Goyal reports no potential conflicts of interest.

SOURCE: Goyal V et al. Lancet Respir Med. 2019;7:791-801.

MADRID – A placebo-controlled trial has confirmed that amoxicillin/clavulanate is beneficial for resolution of acute exacerbations in nonsevere bronchiectasis while also demonstrating a greater relative effect than azithromycin, based on data presented at the annual congress of the European Respiratory Society.

“We now have robust data with which to support our guidelines,” reported Vikas Goyal, MD, of the Children’s Health Clinical Unit, University of Queensland, Brisbane, Australia.

The study addresses a knowledge gap. Antibiotics are already recommended by many guidelines for treatment of acute exacerbations in children with bronchiectasis, but Dr. Goyal said that no controlled trials have ever been performed in this age group to confirm superiority to placebo.

In this multicenter study, called BEST-1, 197 children with bronchiectasis were randomized at the start of an exacerbation to placebo, 45 mg/kg per day of amoxicillin/clavulanate, or 5 mg/kg per day of azithromycin. To maintain blinding, patients in the active treatment groups received a dummy for the opposite antibiotic while patients on placebo received dummies for both active agents.

For the primary outcome, 65% of children randomized to amoxicillin/clavulanate had resolution of their exacerbation by day 14 versus 61% of those randomized to azithromycin and 43% of those randomized to placebo. On the basis of relative risk for reaching this end point, the outcome was superior to placebo for amoxicillin/clavulanate (RR, 1.5; P = .015).

Although the relative risk for azithromycin (RR, 1.4; P = .042) was only slightly lower, it did not reach a prespecified level of significance set at P = .025. Dr. Goyal did report that the resolution rate at 14 days in the placebo group was “higher than expected.”

In this trial, 53% of the 154 children who were tested for respiratory viruses with nasal swabs on day 1 of the exacerbation were found to have respiratory viruses. Of these viruses, rhinovirus was the most common, according to Dr. Goyal, whose data were published just prior to his presentation (Lancet Respir Med. 2019;7:791-801).

The median durations of the exacerbations were 7 days, 8 days, and 10 days for those treated with amoxicillin/clavulanate, azithromycin, and placebo, respectively. The difference between amoxicillin/clavulanate and placebo, but not that between azithromycin and placebo, reached statistical significance, Dr. Goyal said.

There were no between group differences in the time to next exacerbation.

In discussing limitations of this study, Dr. Goyal pointed out that the optimal doses of amoxicillin/clavulanate or azithromycin have never been established for the treatment of exacerbations in children with bronchiectasis. He noted that some infectious disease specialists have advocated higher doses of both than those employed in this trial, but dose-ranging studies have never been conducted in this age group.

In this study, adverse events were less common on azithromycin than amoxicillin/clavulanate (21% vs. 30%), but none were severe, according to Dr. Goyal. He said treatment with azithromycin was associated with increased macrolide-resistant bacteria.

On the basis of these data, Dr. Goyal concluded that amoxicillin/clavulanate should remain, as already specified in some guidelines, the standard first-line therapy for nonsevere exacerbations in nonhospitalized children with bronchiectasis. He recommended reserving azithromycin as an alternative therapy.

Dr. Goyal reports no potential conflicts of interest.

SOURCE: Goyal V et al. Lancet Respir Med. 2019;7:791-801.

MADRID – A placebo-controlled trial has confirmed that amoxicillin/clavulanate is beneficial for resolution of acute exacerbations in nonsevere bronchiectasis while also demonstrating a greater relative effect than azithromycin, based on data presented at the annual congress of the European Respiratory Society.

“We now have robust data with which to support our guidelines,” reported Vikas Goyal, MD, of the Children’s Health Clinical Unit, University of Queensland, Brisbane, Australia.

The study addresses a knowledge gap. Antibiotics are already recommended by many guidelines for treatment of acute exacerbations in children with bronchiectasis, but Dr. Goyal said that no controlled trials have ever been performed in this age group to confirm superiority to placebo.

In this multicenter study, called BEST-1, 197 children with bronchiectasis were randomized at the start of an exacerbation to placebo, 45 mg/kg per day of amoxicillin/clavulanate, or 5 mg/kg per day of azithromycin. To maintain blinding, patients in the active treatment groups received a dummy for the opposite antibiotic while patients on placebo received dummies for both active agents.

For the primary outcome, 65% of children randomized to amoxicillin/clavulanate had resolution of their exacerbation by day 14 versus 61% of those randomized to azithromycin and 43% of those randomized to placebo. On the basis of relative risk for reaching this end point, the outcome was superior to placebo for amoxicillin/clavulanate (RR, 1.5; P = .015).

Although the relative risk for azithromycin (RR, 1.4; P = .042) was only slightly lower, it did not reach a prespecified level of significance set at P = .025. Dr. Goyal did report that the resolution rate at 14 days in the placebo group was “higher than expected.”

In this trial, 53% of the 154 children who were tested for respiratory viruses with nasal swabs on day 1 of the exacerbation were found to have respiratory viruses. Of these viruses, rhinovirus was the most common, according to Dr. Goyal, whose data were published just prior to his presentation (Lancet Respir Med. 2019;7:791-801).

The median durations of the exacerbations were 7 days, 8 days, and 10 days for those treated with amoxicillin/clavulanate, azithromycin, and placebo, respectively. The difference between amoxicillin/clavulanate and placebo, but not that between azithromycin and placebo, reached statistical significance, Dr. Goyal said.

There were no between group differences in the time to next exacerbation.

In discussing limitations of this study, Dr. Goyal pointed out that the optimal doses of amoxicillin/clavulanate or azithromycin have never been established for the treatment of exacerbations in children with bronchiectasis. He noted that some infectious disease specialists have advocated higher doses of both than those employed in this trial, but dose-ranging studies have never been conducted in this age group.

In this study, adverse events were less common on azithromycin than amoxicillin/clavulanate (21% vs. 30%), but none were severe, according to Dr. Goyal. He said treatment with azithromycin was associated with increased macrolide-resistant bacteria.

On the basis of these data, Dr. Goyal concluded that amoxicillin/clavulanate should remain, as already specified in some guidelines, the standard first-line therapy for nonsevere exacerbations in nonhospitalized children with bronchiectasis. He recommended reserving azithromycin as an alternative therapy.

Dr. Goyal reports no potential conflicts of interest.

SOURCE: Goyal V et al. Lancet Respir Med. 2019;7:791-801.

MADRID – In adults with severe chronic rhinosinusitus with nasal polyps (CRSwNP), the monoclonal antibody dupilumab is effective for shrinking the polyps, improving symptoms, and reducing the need for systemic corticosteroids and surgery, according to results of two phase 3 studies reported together at the annual congress of the European Respiratory Society.

“Dupilumab improved all of the disease components, and the improvement was observed in most of them at the first assessment,” reported Jorge F. Máspero, MD, research director, Fundacion Cidea, Buenos Aires.

The data were drawn from multicenter phase 3 trials called LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52. Both included stratifications for asthma and for NSAID-exacerbated respiratory disease (ERD), which are common comorbidities. Findings of the two studies were published together just prior to Dr. Máspero’s presentation at the ERS (Lancet. 2019 Sep 26. doi: 10.1016/S0140-6736(19)31881-1).

For the coprimary end point of endoscopic nasal polyp score (NSP), the reductions were 2.06 and 1.8 at 24 weeks from baseline (both P less than .0001) in SINUS-24 and SINUS-52, respectively. For the nasal congestion or obstruction score, another primary end point, the reductions were 0.89 and 0.87, respectively (both P less than .0001).

There were also major improvements at week 24 on secondary end points, including the Lund-McKay CT score for staging of CRSwNP (P less than .0001), total symptom score (P less than .0001), the UPSIT test for smell (P less than .0001), and SNOT-22 (P less than .0001), a quality of life instrument specific for nasal and sinus diseases.

When these outcomes were graphed, curves for the dupilumab and placebo arms had already separated by 4 weeks, “and then we see the dupilumab patients keep getting better over the course of follow-up, and the effect was seen regardless of comorbidities,” said Dr. Máspero, referring to concomitant asthma or ERD.

The SINUS-24 trial randomly assigned 276 CRSwNP patients to 300 mg dupilumab or placebo, each given subcutaneously every 2 weeks. The SINUS-52 trial, which randomized 448 patients, included the same two arms plus a third arm in which patients also received 300 mg dupilumab every 2 weeks for 24 weeks and then 300 mg every month for an additional 26 weeks.

In a pooled analysis of these trials, patients randomized to dupilumab had a 78% reduction in likelihood of receiving systemic corticosteroids and a 79% reduction in being referred for surgery relative to placebo, Dr. Máspero reported.

Dupilumab, a monoclonal antibody that inhibits the activity of interleukin-4, IL-5, and IL-13, was well tolerated. Among the most common adverse events, there were lower rates of headache (9% vs. 7%), epistaxis (7% vs. 6%), and injection-site erythema (8% vs. 6%) in the dupilumab and placebo arms, respectively, but the rate of serious adverse events (6% vs. 3%) and adverse events leading to treatment discontinuation (5% vs. 3%) were only slightly higher in the active treatment group.

Both trials, which required a bilateral baseline NPS score of 5.0 for entry, recruited a population with relatively severe CRSwNP, according to Dr. Máspero. Of the 724 patients, 204 had ERD.

A restored sense of smell was one of the contributors to an improvement in quality of life.

“The sense of smell improves very quickly after starting dupilumab. Patients reported results within 2 weeks, and there was an almost complete lack of improvement in the placebo group,” Dr. Máspero reported.

Dupilumab is already indicated for the treatment of CRSwNP, but this study confirms a major effect on polyp size, sinus congestion, and symptoms irrespective of the presence of common comorbidities affecting the airways, Dr. Máspero said.

Dr. Maspero reports no potential conflicts of interest.

SOURCE: (Bachert C et al. Lancet. 2019 Sep 26. doi: 10.1016/S0140-6736(19)31881-1.

MADRID – In adults with severe chronic rhinosinusitus with nasal polyps (CRSwNP), the monoclonal antibody dupilumab is effective for shrinking the polyps, improving symptoms, and reducing the need for systemic corticosteroids and surgery, according to results of two phase 3 studies reported together at the annual congress of the European Respiratory Society.

“Dupilumab improved all of the disease components, and the improvement was observed in most of them at the first assessment,” reported Jorge F. Máspero, MD, research director, Fundacion Cidea, Buenos Aires.

The data were drawn from multicenter phase 3 trials called LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52. Both included stratifications for asthma and for NSAID-exacerbated respiratory disease (ERD), which are common comorbidities. Findings of the two studies were published together just prior to Dr. Máspero’s presentation at the ERS (Lancet. 2019 Sep 26. doi: 10.1016/S0140-6736(19)31881-1).

For the coprimary end point of endoscopic nasal polyp score (NSP), the reductions were 2.06 and 1.8 at 24 weeks from baseline (both P less than .0001) in SINUS-24 and SINUS-52, respectively. For the nasal congestion or obstruction score, another primary end point, the reductions were 0.89 and 0.87, respectively (both P less than .0001).

There were also major improvements at week 24 on secondary end points, including the Lund-McKay CT score for staging of CRSwNP (P less than .0001), total symptom score (P less than .0001), the UPSIT test for smell (P less than .0001), and SNOT-22 (P less than .0001), a quality of life instrument specific for nasal and sinus diseases.

When these outcomes were graphed, curves for the dupilumab and placebo arms had already separated by 4 weeks, “and then we see the dupilumab patients keep getting better over the course of follow-up, and the effect was seen regardless of comorbidities,” said Dr. Máspero, referring to concomitant asthma or ERD.

The SINUS-24 trial randomly assigned 276 CRSwNP patients to 300 mg dupilumab or placebo, each given subcutaneously every 2 weeks. The SINUS-52 trial, which randomized 448 patients, included the same two arms plus a third arm in which patients also received 300 mg dupilumab every 2 weeks for 24 weeks and then 300 mg every month for an additional 26 weeks.

In a pooled analysis of these trials, patients randomized to dupilumab had a 78% reduction in likelihood of receiving systemic corticosteroids and a 79% reduction in being referred for surgery relative to placebo, Dr. Máspero reported.

Dupilumab, a monoclonal antibody that inhibits the activity of interleukin-4, IL-5, and IL-13, was well tolerated. Among the most common adverse events, there were lower rates of headache (9% vs. 7%), epistaxis (7% vs. 6%), and injection-site erythema (8% vs. 6%) in the dupilumab and placebo arms, respectively, but the rate of serious adverse events (6% vs. 3%) and adverse events leading to treatment discontinuation (5% vs. 3%) were only slightly higher in the active treatment group.

Both trials, which required a bilateral baseline NPS score of 5.0 for entry, recruited a population with relatively severe CRSwNP, according to Dr. Máspero. Of the 724 patients, 204 had ERD.

A restored sense of smell was one of the contributors to an improvement in quality of life.

“The sense of smell improves very quickly after starting dupilumab. Patients reported results within 2 weeks, and there was an almost complete lack of improvement in the placebo group,” Dr. Máspero reported.

Dupilumab is already indicated for the treatment of CRSwNP, but this study confirms a major effect on polyp size, sinus congestion, and symptoms irrespective of the presence of common comorbidities affecting the airways, Dr. Máspero said.

Dr. Maspero reports no potential conflicts of interest.

SOURCE: (Bachert C et al. Lancet. 2019 Sep 26. doi: 10.1016/S0140-6736(19)31881-1.

MADRID – In adults with severe chronic rhinosinusitus with nasal polyps (CRSwNP), the monoclonal antibody dupilumab is effective for shrinking the polyps, improving symptoms, and reducing the need for systemic corticosteroids and surgery, according to results of two phase 3 studies reported together at the annual congress of the European Respiratory Society.

“Dupilumab improved all of the disease components, and the improvement was observed in most of them at the first assessment,” reported Jorge F. Máspero, MD, research director, Fundacion Cidea, Buenos Aires.

The data were drawn from multicenter phase 3 trials called LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52. Both included stratifications for asthma and for NSAID-exacerbated respiratory disease (ERD), which are common comorbidities. Findings of the two studies were published together just prior to Dr. Máspero’s presentation at the ERS (Lancet. 2019 Sep 26. doi: 10.1016/S0140-6736(19)31881-1).

For the coprimary end point of endoscopic nasal polyp score (NSP), the reductions were 2.06 and 1.8 at 24 weeks from baseline (both P less than .0001) in SINUS-24 and SINUS-52, respectively. For the nasal congestion or obstruction score, another primary end point, the reductions were 0.89 and 0.87, respectively (both P less than .0001).

There were also major improvements at week 24 on secondary end points, including the Lund-McKay CT score for staging of CRSwNP (P less than .0001), total symptom score (P less than .0001), the UPSIT test for smell (P less than .0001), and SNOT-22 (P less than .0001), a quality of life instrument specific for nasal and sinus diseases.

When these outcomes were graphed, curves for the dupilumab and placebo arms had already separated by 4 weeks, “and then we see the dupilumab patients keep getting better over the course of follow-up, and the effect was seen regardless of comorbidities,” said Dr. Máspero, referring to concomitant asthma or ERD.

The SINUS-24 trial randomly assigned 276 CRSwNP patients to 300 mg dupilumab or placebo, each given subcutaneously every 2 weeks. The SINUS-52 trial, which randomized 448 patients, included the same two arms plus a third arm in which patients also received 300 mg dupilumab every 2 weeks for 24 weeks and then 300 mg every month for an additional 26 weeks.

In a pooled analysis of these trials, patients randomized to dupilumab had a 78% reduction in likelihood of receiving systemic corticosteroids and a 79% reduction in being referred for surgery relative to placebo, Dr. Máspero reported.

Dupilumab, a monoclonal antibody that inhibits the activity of interleukin-4, IL-5, and IL-13, was well tolerated. Among the most common adverse events, there were lower rates of headache (9% vs. 7%), epistaxis (7% vs. 6%), and injection-site erythema (8% vs. 6%) in the dupilumab and placebo arms, respectively, but the rate of serious adverse events (6% vs. 3%) and adverse events leading to treatment discontinuation (5% vs. 3%) were only slightly higher in the active treatment group.

Both trials, which required a bilateral baseline NPS score of 5.0 for entry, recruited a population with relatively severe CRSwNP, according to Dr. Máspero. Of the 724 patients, 204 had ERD.

A restored sense of smell was one of the contributors to an improvement in quality of life.

“The sense of smell improves very quickly after starting dupilumab. Patients reported results within 2 weeks, and there was an almost complete lack of improvement in the placebo group,” Dr. Máspero reported.

Dupilumab is already indicated for the treatment of CRSwNP, but this study confirms a major effect on polyp size, sinus congestion, and symptoms irrespective of the presence of common comorbidities affecting the airways, Dr. Máspero said.

Dr. Maspero reports no potential conflicts of interest.

SOURCE: (Bachert C et al. Lancet. 2019 Sep 26. doi: 10.1016/S0140-6736(19)31881-1.

MADRID – In patients managed on mechanical ventilation in an intensive care unit following cardiac surgery, a fully automated system provides more reliable ventilatory support than highly experienced ICU nurses, suggest results of a randomized trial.

The study’s control group received usual care, which means that nurses adjusted mechanical ventilation manually in response to respiratory rate, tidal volume, positive end-respiratory pressure (PEEP), and other factors to maintain ventilation within parameters associated with safe respiration. The experimental group was managed with a fully automated closed-loop system to make these adjustments without any nurse intervention.

For those in the experimental group “the proportion of time in the optimal zone was increased and the proportion of time in the unsafe zone was decreased” relative to those randomized to conventional nursing care, Marcus J. Schultz, MD, reported at the annual congress of the European Respiratory Society.

Conducted at a hospital with an experienced ICU staff, the study had a control arm that was managed by “dedicated nurses who, I can tell you, are very eager to provide the best level of care possible,” said Dr. Schultz, professor of experimental intensive care, University of Amsterdam, the Netherlands..

The investigator-initiated POSITiVE trial randomized 220 cardiac surgery patients scheduled to receive postoperative mechanical ventilation in the ICU. Exclusions included those with class III or higher chronic obstructive pulmonary disease (COPD), a requirement for extracorporeal membrane oxygenation (ECMO), or a history of lung surgery.

The primary endpoint was the proportion of time spent in an optimal zone, an acceptable zone, or a dangerous zone of ventilation based on predefined values for tidal volume, maximum airway pressure, end-tidal CO₂, and oxygen saturation (SpO₂).

The greatest between-group difference was seen in the proportion of time spent in the optimal zone. This climbed from approximately 35% in the control arm to slightly more than 70% in the experimental arm, a significant difference. The proportion of time in the dangerous zone was reduced from approximately 6% in the control arm to 3% in the automated arm. On average nurse-managed patients spent nearly 60% of the time in the acceptable zone versus less than 30% of those in the automated experimental arm.

A heat map using green, yellow, and red to represent optimal, acceptable, and dangerous zones, respectively, for individual participants in the trial provided a more stark global impression. For the control group, the heat map was primarily yellow with scattered dashes of green and red. For the experimental group, the map was primarily green with dashes of yellow and a much smaller number of red dashes relative to the control group.

In addition, the time to spontaneous breathing was 38% shorter for those randomized to automated ventilation than to conventional care, a significant difference.

There are now many devices marketed for automated ventilation, according to Dr. Schultz. The device used in this study was the proprietary INTELLiVENT-ASV system, marketed by Hamilton Medical, which was selected based on prior satisfactory experience. Although not unique, this system has sophisticated software to adjust ventilation to reach targets set by the clinician on the basis of information it is receiving from physiologic sensors for such variables as respiratory rate, tidal volume, and inspiratory pressure.

“It is frequently adjusting the PEEP levels to reach the lowest driving pressure,” said Dr. Schultz. Among its many other features, it also “gives spontaneous breathing trials automatically.”

Uncomplicated patients were selected purposefully to test this system, but Dr. Schultz said that a second trial, called POSITiVE 2, is now being planned that will enroll more complex patients. Keeping complex patients within the optimal zone as defined by tidal volume and other critical variables has the potential to reduce the lung damage that is known to occur when these are not optimized.

“Applying safe ventilatory support in clinical practice remains a serious challenge and is extremely time consuming,” Dr. Schultz said. He reported that fully automated ventilation appears to be reliable, and “it takes out the human factor” in regard to diligence in monitoring and potential for error.

Overall, these results support the potential for a fully automated system to improve optimal ventilatory support, reduce risk of lung injury, and reduce staffing required for monitoring of mechanical ventilation, according to Dr. Schultz.

Relative costs were not evaluated in this analysis, but might be another factor relevant to the value of fully automated ventilation in ICU patients.
 

MADRID – In patients managed on mechanical ventilation in an intensive care unit following cardiac surgery, a fully automated system provides more reliable ventilatory support than highly experienced ICU nurses, suggest results of a randomized trial.

The study’s control group received usual care, which means that nurses adjusted mechanical ventilation manually in response to respiratory rate, tidal volume, positive end-respiratory pressure (PEEP), and other factors to maintain ventilation within parameters associated with safe respiration. The experimental group was managed with a fully automated closed-loop system to make these adjustments without any nurse intervention.

For those in the experimental group “the proportion of time in the optimal zone was increased and the proportion of time in the unsafe zone was decreased” relative to those randomized to conventional nursing care, Marcus J. Schultz, MD, reported at the annual congress of the European Respiratory Society.

Conducted at a hospital with an experienced ICU staff, the study had a control arm that was managed by “dedicated nurses who, I can tell you, are very eager to provide the best level of care possible,” said Dr. Schultz, professor of experimental intensive care, University of Amsterdam, the Netherlands..

The investigator-initiated POSITiVE trial randomized 220 cardiac surgery patients scheduled to receive postoperative mechanical ventilation in the ICU. Exclusions included those with class III or higher chronic obstructive pulmonary disease (COPD), a requirement for extracorporeal membrane oxygenation (ECMO), or a history of lung surgery.

The primary endpoint was the proportion of time spent in an optimal zone, an acceptable zone, or a dangerous zone of ventilation based on predefined values for tidal volume, maximum airway pressure, end-tidal CO₂, and oxygen saturation (SpO₂).

The greatest between-group difference was seen in the proportion of time spent in the optimal zone. This climbed from approximately 35% in the control arm to slightly more than 70% in the experimental arm, a significant difference. The proportion of time in the dangerous zone was reduced from approximately 6% in the control arm to 3% in the automated arm. On average nurse-managed patients spent nearly 60% of the time in the acceptable zone versus less than 30% of those in the automated experimental arm.

A heat map using green, yellow, and red to represent optimal, acceptable, and dangerous zones, respectively, for individual participants in the trial provided a more stark global impression. For the control group, the heat map was primarily yellow with scattered dashes of green and red. For the experimental group, the map was primarily green with dashes of yellow and a much smaller number of red dashes relative to the control group.

In addition, the time to spontaneous breathing was 38% shorter for those randomized to automated ventilation than to conventional care, a significant difference.

There are now many devices marketed for automated ventilation, according to Dr. Schultz. The device used in this study was the proprietary INTELLiVENT-ASV system, marketed by Hamilton Medical, which was selected based on prior satisfactory experience. Although not unique, this system has sophisticated software to adjust ventilation to reach targets set by the clinician on the basis of information it is receiving from physiologic sensors for such variables as respiratory rate, tidal volume, and inspiratory pressure.

“It is frequently adjusting the PEEP levels to reach the lowest driving pressure,” said Dr. Schultz. Among its many other features, it also “gives spontaneous breathing trials automatically.”

Uncomplicated patients were selected purposefully to test this system, but Dr. Schultz said that a second trial, called POSITiVE 2, is now being planned that will enroll more complex patients. Keeping complex patients within the optimal zone as defined by tidal volume and other critical variables has the potential to reduce the lung damage that is known to occur when these are not optimized.

“Applying safe ventilatory support in clinical practice remains a serious challenge and is extremely time consuming,” Dr. Schultz said. He reported that fully automated ventilation appears to be reliable, and “it takes out the human factor” in regard to diligence in monitoring and potential for error.

Overall, these results support the potential for a fully automated system to improve optimal ventilatory support, reduce risk of lung injury, and reduce staffing required for monitoring of mechanical ventilation, according to Dr. Schultz.

Relative costs were not evaluated in this analysis, but might be another factor relevant to the value of fully automated ventilation in ICU patients.
 

MADRID – In patients managed on mechanical ventilation in an intensive care unit following cardiac surgery, a fully automated system provides more reliable ventilatory support than highly experienced ICU nurses, suggest results of a randomized trial.

The study’s control group received usual care, which means that nurses adjusted mechanical ventilation manually in response to respiratory rate, tidal volume, positive end-respiratory pressure (PEEP), and other factors to maintain ventilation within parameters associated with safe respiration. The experimental group was managed with a fully automated closed-loop system to make these adjustments without any nurse intervention.

For those in the experimental group “the proportion of time in the optimal zone was increased and the proportion of time in the unsafe zone was decreased” relative to those randomized to conventional nursing care, Marcus J. Schultz, MD, reported at the annual congress of the European Respiratory Society.

Conducted at a hospital with an experienced ICU staff, the study had a control arm that was managed by “dedicated nurses who, I can tell you, are very eager to provide the best level of care possible,” said Dr. Schultz, professor of experimental intensive care, University of Amsterdam, the Netherlands..

The investigator-initiated POSITiVE trial randomized 220 cardiac surgery patients scheduled to receive postoperative mechanical ventilation in the ICU. Exclusions included those with class III or higher chronic obstructive pulmonary disease (COPD), a requirement for extracorporeal membrane oxygenation (ECMO), or a history of lung surgery.

The primary endpoint was the proportion of time spent in an optimal zone, an acceptable zone, or a dangerous zone of ventilation based on predefined values for tidal volume, maximum airway pressure, end-tidal CO₂, and oxygen saturation (SpO₂).

The greatest between-group difference was seen in the proportion of time spent in the optimal zone. This climbed from approximately 35% in the control arm to slightly more than 70% in the experimental arm, a significant difference. The proportion of time in the dangerous zone was reduced from approximately 6% in the control arm to 3% in the automated arm. On average nurse-managed patients spent nearly 60% of the time in the acceptable zone versus less than 30% of those in the automated experimental arm.

A heat map using green, yellow, and red to represent optimal, acceptable, and dangerous zones, respectively, for individual participants in the trial provided a more stark global impression. For the control group, the heat map was primarily yellow with scattered dashes of green and red. For the experimental group, the map was primarily green with dashes of yellow and a much smaller number of red dashes relative to the control group.

In addition, the time to spontaneous breathing was 38% shorter for those randomized to automated ventilation than to conventional care, a significant difference.

There are now many devices marketed for automated ventilation, according to Dr. Schultz. The device used in this study was the proprietary INTELLiVENT-ASV system, marketed by Hamilton Medical, which was selected based on prior satisfactory experience. Although not unique, this system has sophisticated software to adjust ventilation to reach targets set by the clinician on the basis of information it is receiving from physiologic sensors for such variables as respiratory rate, tidal volume, and inspiratory pressure.

“It is frequently adjusting the PEEP levels to reach the lowest driving pressure,” said Dr. Schultz. Among its many other features, it also “gives spontaneous breathing trials automatically.”

Uncomplicated patients were selected purposefully to test this system, but Dr. Schultz said that a second trial, called POSITiVE 2, is now being planned that will enroll more complex patients. Keeping complex patients within the optimal zone as defined by tidal volume and other critical variables has the potential to reduce the lung damage that is known to occur when these are not optimized.

“Applying safe ventilatory support in clinical practice remains a serious challenge and is extremely time consuming,” Dr. Schultz said. He reported that fully automated ventilation appears to be reliable, and “it takes out the human factor” in regard to diligence in monitoring and potential for error.

Overall, these results support the potential for a fully automated system to improve optimal ventilatory support, reduce risk of lung injury, and reduce staffing required for monitoring of mechanical ventilation, according to Dr. Schultz.

Relative costs were not evaluated in this analysis, but might be another factor relevant to the value of fully automated ventilation in ICU patients.
 

MADRID – Low-dose azithromycin prophylaxis significantly reduced exacerbations and hospitalizations in patients with primary antibody deficiency relative to placebo, according to a randomized multicenter phase 2 trial.

The study results support routine use of low-dose azithromycin in patients with primary antibody deficiency, according to Cinzia Milito, MD, PhD, department of molecular medicine, Sapienza University, Rome. Perhaps more importantly, the long-term benefits might be even greater.

“In patients with primary antibody deficiency, the respiratory tract is the major target of acute infections, leading to inflammation, increased airway reactivity, and over time to tissue remodeling and chronic lung disease,” Dr. Milito said at the annual congress of the European Respiratory Society. “Chronic lung disease is a major cause of death in this population.”

In this study 89 patients with primary antibody deficiency were randomized at seven centers in Italy to 250 mg per day of azithromycin or placebo administered on three consecutive days of each week for three years. Patients were maintained on other treatments, such as IgG replacement.

At the end of study, 33 of the 44 patients randomized to azithromycin and 34 of the 45 patients randomized to placebo remained on therapy. When compared for the primary endpoint of exacerbations, the median incidence rates were 3.6 episodes in the azithromycin group and 5.2 episodes in the placebo group, providing a 1.6 episode or 31% relative reduction (P=0.02).

The median number of hospitalizations for any cause, which was a secondary endpoint, was also significantly lower in the azithromycin arm (0.1 vs. 0.3 episodes).

In addition, the number of additional courses of antibiotics was significantly lower (2.3 vs. 3.6), and the time to the first course of antibiotic course was significantly longer (181.5 vs. 122.4 days) in the azithromycin group, reported Dr. Milito, whose study is now published (Milito C et al. J Allergy Clin Immunol 2019;144: 584-593).

“In a six-month washout at the end of the study, the relative advantages seen for azithromycin were lost,” Dr. Milito said.

Quality of life measured with the St. George’s Respiratory Questionnaire showed an association between low-dose azithromycin prophylaxis and significant improvement in the symptom domain when evaluated during and at the end of the study. Improvement on the Short-Form 36, which was observed one year into the study, was no longer significant at the end of the study.

Azithromycin was well tolerated with no significant differences in the rate of serious adverse events observed between the experimental and control arms of the study. Over the course of the study, however, azithromycin was associated with a significant protective effect against diarrhea (13% vs. 53%) and acute rhinosinusitus (4% vs. 27%).

There was no observed increase in macrolide resistance associated with azithromycin prophylaxis.

Macrolides have been evaluated for preventing progression of several chronic lung diseases, including chronic obstructive pulmonary disease, bronchiectasis, and cystic fibrosis. Like other drugs in its class, “azithromycin, in addition to its antimicrobial effect, has anti-inflammatory properties,” Dr. Milito said. This increases its potential to slow the time to airway damage in patients with primary antibiotic deficiency.

“Chronic lung disease is the result of a vicious cycle that begins with the inflammatory response to infection,” Dr. Milito explained. On the basis of these data, she believes azithromycin “should be considered a valuable addition to usual treatment” for primary antibody deficiencies.
 

SOURCE: EUROPEAN RESPIRATORY SOCIETY 2019 INTERNATIONAL CONGRESS

MADRID – Low-dose azithromycin prophylaxis significantly reduced exacerbations and hospitalizations in patients with primary antibody deficiency relative to placebo, according to a randomized multicenter phase 2 trial.

The study results support routine use of low-dose azithromycin in patients with primary antibody deficiency, according to Cinzia Milito, MD, PhD, department of molecular medicine, Sapienza University, Rome. Perhaps more importantly, the long-term benefits might be even greater.

“In patients with primary antibody deficiency, the respiratory tract is the major target of acute infections, leading to inflammation, increased airway reactivity, and over time to tissue remodeling and chronic lung disease,” Dr. Milito said at the annual congress of the European Respiratory Society. “Chronic lung disease is a major cause of death in this population.”

In this study 89 patients with primary antibody deficiency were randomized at seven centers in Italy to 250 mg per day of azithromycin or placebo administered on three consecutive days of each week for three years. Patients were maintained on other treatments, such as IgG replacement.

At the end of study, 33 of the 44 patients randomized to azithromycin and 34 of the 45 patients randomized to placebo remained on therapy. When compared for the primary endpoint of exacerbations, the median incidence rates were 3.6 episodes in the azithromycin group and 5.2 episodes in the placebo group, providing a 1.6 episode or 31% relative reduction (P=0.02).

The median number of hospitalizations for any cause, which was a secondary endpoint, was also significantly lower in the azithromycin arm (0.1 vs. 0.3 episodes).

In addition, the number of additional courses of antibiotics was significantly lower (2.3 vs. 3.6), and the time to the first course of antibiotic course was significantly longer (181.5 vs. 122.4 days) in the azithromycin group, reported Dr. Milito, whose study is now published (Milito C et al. J Allergy Clin Immunol 2019;144: 584-593).

“In a six-month washout at the end of the study, the relative advantages seen for azithromycin were lost,” Dr. Milito said.

Quality of life measured with the St. George’s Respiratory Questionnaire showed an association between low-dose azithromycin prophylaxis and significant improvement in the symptom domain when evaluated during and at the end of the study. Improvement on the Short-Form 36, which was observed one year into the study, was no longer significant at the end of the study.

Azithromycin was well tolerated with no significant differences in the rate of serious adverse events observed between the experimental and control arms of the study. Over the course of the study, however, azithromycin was associated with a significant protective effect against diarrhea (13% vs. 53%) and acute rhinosinusitus (4% vs. 27%).

There was no observed increase in macrolide resistance associated with azithromycin prophylaxis.

Macrolides have been evaluated for preventing progression of several chronic lung diseases, including chronic obstructive pulmonary disease, bronchiectasis, and cystic fibrosis. Like other drugs in its class, “azithromycin, in addition to its antimicrobial effect, has anti-inflammatory properties,” Dr. Milito said. This increases its potential to slow the time to airway damage in patients with primary antibiotic deficiency.

“Chronic lung disease is the result of a vicious cycle that begins with the inflammatory response to infection,” Dr. Milito explained. On the basis of these data, she believes azithromycin “should be considered a valuable addition to usual treatment” for primary antibody deficiencies.
 

SOURCE: EUROPEAN RESPIRATORY SOCIETY 2019 INTERNATIONAL CONGRESS

MADRID – Low-dose azithromycin prophylaxis significantly reduced exacerbations and hospitalizations in patients with primary antibody deficiency relative to placebo, according to a randomized multicenter phase 2 trial.

The study results support routine use of low-dose azithromycin in patients with primary antibody deficiency, according to Cinzia Milito, MD, PhD, department of molecular medicine, Sapienza University, Rome. Perhaps more importantly, the long-term benefits might be even greater.

“In patients with primary antibody deficiency, the respiratory tract is the major target of acute infections, leading to inflammation, increased airway reactivity, and over time to tissue remodeling and chronic lung disease,” Dr. Milito said at the annual congress of the European Respiratory Society. “Chronic lung disease is a major cause of death in this population.”

In this study 89 patients with primary antibody deficiency were randomized at seven centers in Italy to 250 mg per day of azithromycin or placebo administered on three consecutive days of each week for three years. Patients were maintained on other treatments, such as IgG replacement.

At the end of study, 33 of the 44 patients randomized to azithromycin and 34 of the 45 patients randomized to placebo remained on therapy. When compared for the primary endpoint of exacerbations, the median incidence rates were 3.6 episodes in the azithromycin group and 5.2 episodes in the placebo group, providing a 1.6 episode or 31% relative reduction (P=0.02).

The median number of hospitalizations for any cause, which was a secondary endpoint, was also significantly lower in the azithromycin arm (0.1 vs. 0.3 episodes).

In addition, the number of additional courses of antibiotics was significantly lower (2.3 vs. 3.6), and the time to the first course of antibiotic course was significantly longer (181.5 vs. 122.4 days) in the azithromycin group, reported Dr. Milito, whose study is now published (Milito C et al. J Allergy Clin Immunol 2019;144: 584-593).

“In a six-month washout at the end of the study, the relative advantages seen for azithromycin were lost,” Dr. Milito said.

Quality of life measured with the St. George’s Respiratory Questionnaire showed an association between low-dose azithromycin prophylaxis and significant improvement in the symptom domain when evaluated during and at the end of the study. Improvement on the Short-Form 36, which was observed one year into the study, was no longer significant at the end of the study.

Azithromycin was well tolerated with no significant differences in the rate of serious adverse events observed between the experimental and control arms of the study. Over the course of the study, however, azithromycin was associated with a significant protective effect against diarrhea (13% vs. 53%) and acute rhinosinusitus (4% vs. 27%).

There was no observed increase in macrolide resistance associated with azithromycin prophylaxis.

Macrolides have been evaluated for preventing progression of several chronic lung diseases, including chronic obstructive pulmonary disease, bronchiectasis, and cystic fibrosis. Like other drugs in its class, “azithromycin, in addition to its antimicrobial effect, has anti-inflammatory properties,” Dr. Milito said. This increases its potential to slow the time to airway damage in patients with primary antibiotic deficiency.

“Chronic lung disease is the result of a vicious cycle that begins with the inflammatory response to infection,” Dr. Milito explained. On the basis of these data, she believes azithromycin “should be considered a valuable addition to usual treatment” for primary antibody deficiencies.
 

SOURCE: EUROPEAN RESPIRATORY SOCIETY 2019 INTERNATIONAL CONGRESS

MADRID – Consistent with previous evidence of higher relative rates of drug delivery, mesh nebulizers offer several advantages over jet nebulizers for treatment of acute asthma in children presenting to an emergency department, according to results of a randomized trial presented at the annual congress of the European Respiratory Society.

For the primary outcome of hospital admission, the advantage of the mesh over the jet nebulizer only reached significance when used with a mask, rather than a valve, but trial results overall support the conclusion that the mesh device delivers drug more efficiently, according to Gerald Moody, RRT-NPS, clinical research coordinator at Children’s Medical Center, Dallas.

In this multicenter, single-blinded trial, 217 children presenting to an ED with acute asthma of moderate or greater severity were randomized to receive bronchodilator treatment delivered with a mesh device or a jet device. For drug delivery, aerosol masks or mouthpiece valves were permitted and selected at the discretion of the clinician administrating treatment. Masks were used in 80% of cases.

Patients remained in the study until either symptom control was achieved or a decision was reached to advise hospital admission. Patients with complex comorbidities or who had received oral corticosteroids within the previous 24 hours were excluded.

For the primary outcome of hospital discharge, the 31% reduction (P = .22) in hospitalization in favor of the mesh nebulizer failed to reach statistical significance. Although the study is likely to have been underpowered, Mr. Moody also pointed out an uneven distribution in severity of disease at baseline. In addition to a significantly higher median asthma score (9.0 vs. 8.0; P = .042) in the mesh nebulizer group, there was also a significantly higher percentage with severe disease (57% vs. 42%; P = .025).

“There were no significant differences in any of the other variables we evaluated, such as age, gender, race, or body mass index,” Mr. Moody reported.

Despite the higher disease burden in the mesh nebulizer group, there was a 48% reduction (P = .03) in hospital admissions among those randomized to the mesh nebulizer when both groups received treatment through a mask.

In addition, those treated with the mask required on average only two treatments before achieving symptom control whether they met criteria for moderate or severe asthma at baseline. The median numbers of treatments in the jet nebulizer group for moderate and severe asthma were 3 and 3.5, respectively.

In previous experimental studies, which ultimately provided the rationale for this trial, the estimated amount of drug reaching the airways with a mesh nebulizer was approximately twice as great as that estimated in the model when delivery was performed with a jet device, according to Mr. Moody.

This study appeared to corroborate that advantage. Both the median doses of albuterol (10 mg vs. 15 mg) and ipratropium (1,000 mcg vs. 1,500 mcg) were significantly lower (P less than .001 for both) among the patients randomized to the mesh nebulizer.

Although the jet nebulizers are widely employed “for their ease of use and low cost,” Mr. Moody characterized mesh nebulizers as an advance in technology. In this study, which Mr. Moody said is the first to evaluate whether the experimental evidence of greater drug delivery efficiency translates into a clinical advantage, the primary endpoint was missed, but Mr. Moody indicated that the overall findings support the potential for a difference.

The ERS-invited discussant on this study, Celeste Michala Porsbjerg, MD, Bispebjerg Hospital, Copenhagen University, expressed a concern that might deserve attention in a larger trial. Based on the premise that more efficient delivery increases drug exposure, she questioned whether it might not also increase risks.

There were no significant treatment-related adverse events reported in either arm of this study, Mr. Moody responded, but he conceded that this is an appropriate focus of attention for future studies.

Mr. Moody reported a financial relationship with Aerogen, which produces the mesh device tested in this trial.

MADRID – Consistent with previous evidence of higher relative rates of drug delivery, mesh nebulizers offer several advantages over jet nebulizers for treatment of acute asthma in children presenting to an emergency department, according to results of a randomized trial presented at the annual congress of the European Respiratory Society.

For the primary outcome of hospital admission, the advantage of the mesh over the jet nebulizer only reached significance when used with a mask, rather than a valve, but trial results overall support the conclusion that the mesh device delivers drug more efficiently, according to Gerald Moody, RRT-NPS, clinical research coordinator at Children’s Medical Center, Dallas.

In this multicenter, single-blinded trial, 217 children presenting to an ED with acute asthma of moderate or greater severity were randomized to receive bronchodilator treatment delivered with a mesh device or a jet device. For drug delivery, aerosol masks or mouthpiece valves were permitted and selected at the discretion of the clinician administrating treatment. Masks were used in 80% of cases.

Patients remained in the study until either symptom control was achieved or a decision was reached to advise hospital admission. Patients with complex comorbidities or who had received oral corticosteroids within the previous 24 hours were excluded.

For the primary outcome of hospital discharge, the 31% reduction (P = .22) in hospitalization in favor of the mesh nebulizer failed to reach statistical significance. Although the study is likely to have been underpowered, Mr. Moody also pointed out an uneven distribution in severity of disease at baseline. In addition to a significantly higher median asthma score (9.0 vs. 8.0; P = .042) in the mesh nebulizer group, there was also a significantly higher percentage with severe disease (57% vs. 42%; P = .025).

“There were no significant differences in any of the other variables we evaluated, such as age, gender, race, or body mass index,” Mr. Moody reported.

Despite the higher disease burden in the mesh nebulizer group, there was a 48% reduction (P = .03) in hospital admissions among those randomized to the mesh nebulizer when both groups received treatment through a mask.

In addition, those treated with the mask required on average only two treatments before achieving symptom control whether they met criteria for moderate or severe asthma at baseline. The median numbers of treatments in the jet nebulizer group for moderate and severe asthma were 3 and 3.5, respectively.

In previous experimental studies, which ultimately provided the rationale for this trial, the estimated amount of drug reaching the airways with a mesh nebulizer was approximately twice as great as that estimated in the model when delivery was performed with a jet device, according to Mr. Moody.

This study appeared to corroborate that advantage. Both the median doses of albuterol (10 mg vs. 15 mg) and ipratropium (1,000 mcg vs. 1,500 mcg) were significantly lower (P less than .001 for both) among the patients randomized to the mesh nebulizer.

Although the jet nebulizers are widely employed “for their ease of use and low cost,” Mr. Moody characterized mesh nebulizers as an advance in technology. In this study, which Mr. Moody said is the first to evaluate whether the experimental evidence of greater drug delivery efficiency translates into a clinical advantage, the primary endpoint was missed, but Mr. Moody indicated that the overall findings support the potential for a difference.

The ERS-invited discussant on this study, Celeste Michala Porsbjerg, MD, Bispebjerg Hospital, Copenhagen University, expressed a concern that might deserve attention in a larger trial. Based on the premise that more efficient delivery increases drug exposure, she questioned whether it might not also increase risks.

There were no significant treatment-related adverse events reported in either arm of this study, Mr. Moody responded, but he conceded that this is an appropriate focus of attention for future studies.

Mr. Moody reported a financial relationship with Aerogen, which produces the mesh device tested in this trial.

MADRID – Consistent with previous evidence of higher relative rates of drug delivery, mesh nebulizers offer several advantages over jet nebulizers for treatment of acute asthma in children presenting to an emergency department, according to results of a randomized trial presented at the annual congress of the European Respiratory Society.

For the primary outcome of hospital admission, the advantage of the mesh over the jet nebulizer only reached significance when used with a mask, rather than a valve, but trial results overall support the conclusion that the mesh device delivers drug more efficiently, according to Gerald Moody, RRT-NPS, clinical research coordinator at Children’s Medical Center, Dallas.

In this multicenter, single-blinded trial, 217 children presenting to an ED with acute asthma of moderate or greater severity were randomized to receive bronchodilator treatment delivered with a mesh device or a jet device. For drug delivery, aerosol masks or mouthpiece valves were permitted and selected at the discretion of the clinician administrating treatment. Masks were used in 80% of cases.

Patients remained in the study until either symptom control was achieved or a decision was reached to advise hospital admission. Patients with complex comorbidities or who had received oral corticosteroids within the previous 24 hours were excluded.

For the primary outcome of hospital discharge, the 31% reduction (P = .22) in hospitalization in favor of the mesh nebulizer failed to reach statistical significance. Although the study is likely to have been underpowered, Mr. Moody also pointed out an uneven distribution in severity of disease at baseline. In addition to a significantly higher median asthma score (9.0 vs. 8.0; P = .042) in the mesh nebulizer group, there was also a significantly higher percentage with severe disease (57% vs. 42%; P = .025).

“There were no significant differences in any of the other variables we evaluated, such as age, gender, race, or body mass index,” Mr. Moody reported.

Despite the higher disease burden in the mesh nebulizer group, there was a 48% reduction (P = .03) in hospital admissions among those randomized to the mesh nebulizer when both groups received treatment through a mask.

In addition, those treated with the mask required on average only two treatments before achieving symptom control whether they met criteria for moderate or severe asthma at baseline. The median numbers of treatments in the jet nebulizer group for moderate and severe asthma were 3 and 3.5, respectively.

In previous experimental studies, which ultimately provided the rationale for this trial, the estimated amount of drug reaching the airways with a mesh nebulizer was approximately twice as great as that estimated in the model when delivery was performed with a jet device, according to Mr. Moody.

This study appeared to corroborate that advantage. Both the median doses of albuterol (10 mg vs. 15 mg) and ipratropium (1,000 mcg vs. 1,500 mcg) were significantly lower (P less than .001 for both) among the patients randomized to the mesh nebulizer.

Although the jet nebulizers are widely employed “for their ease of use and low cost,” Mr. Moody characterized mesh nebulizers as an advance in technology. In this study, which Mr. Moody said is the first to evaluate whether the experimental evidence of greater drug delivery efficiency translates into a clinical advantage, the primary endpoint was missed, but Mr. Moody indicated that the overall findings support the potential for a difference.

The ERS-invited discussant on this study, Celeste Michala Porsbjerg, MD, Bispebjerg Hospital, Copenhagen University, expressed a concern that might deserve attention in a larger trial. Based on the premise that more efficient delivery increases drug exposure, she questioned whether it might not also increase risks.

There were no significant treatment-related adverse events reported in either arm of this study, Mr. Moody responded, but he conceded that this is an appropriate focus of attention for future studies.

Mr. Moody reported a financial relationship with Aerogen, which produces the mesh device tested in this trial.

NEW YORK – For women with pseudofolliculitis barbae, an empirically-based strategy of microdermabrasion, laser treatment, emollients, and maintenance retinoids has been found highly effective, Wendy Roberts, MD, reported at the Skin of Color Update 2019.

“We didn’t have great treatments for this problem in the past, but the technology has evolved, and you can now get most women clear,” Dr. Roberts, a dermatologist who practices in Rancho Mirage, Calif., said at the meeting.

This approach is appropriate in all women, but Dr. Roberts focused on her experience with black patients, for whom an antioxidant cream is added to address the inflammatory-associated hyperpigmentation that often accompanies pseudofolliculitis barbae, a chronic inflammatory skin condition typically characterized by small, painful papules and pustules.

Start with microdermabrasion to treat the hypertrophic hair follicles and address keratin plugs, Dr. Roberts said. The microdermabrasion smooths the skin and increases penetration of subsequent creams and topics, she said.

“In the same session, I treat with Nd-YAG 1064 nm laser using short pulses,” she noted. For black women, she makes four passes with the laser at a level of moderate intensity. For those with lighter skin, she might perform as many as six passes with the laser set higher.

The microdermabrasion is repeated monthly for three or four treatments, but can be extended for those with persistent symptoms, Dr. Roberts pointed out. She presented a case of a patient who required seven treatments to achieve a satisfactory response.

Patients are instructed to avoid hair plucking and over the course of treatment nightly topical tretinoin is recommended for maintenance. Regular use of emollients is also recommended. For black women who have developed hyperpigmentation as a complication of pseudofolliculitis barbae, Dr. Roberts prescribes a lightening cream.

“I have pretty much moved away from hydroquinone,” said Dr. Roberts, explaining that she has achieved better results with topical cysteamine, a product that she has been using for about 3 years.

In outlining her treatment strategy, she employed case studies of two black women, both of whom achieved resolution of the problem and were satisfied with the results. She said that the same approach is suitable for women of other racial and ethnic groups.

Most commonly seen in black men, pseudofolliculitis barbae – also known as razor bumps – can occur as a complication of shaving in men or women from any racial and ethnic group. However, because of their embarrassment, women often fail to volunteer that they are struggling with this problem. Some women have been afflicted for years and have developed a regular routine of shaving or plucking hairs and then applying makeup for camouflage, Dr. Roberts said.

“This is a patient who rarely presents the problem to the dermatologist. Yet, she is in every one of our practices,” she added. Due to the frequency with which she has identified pseudofolliculitis barbae in patients who are being seen for a different complaint, she now routinely asks patients about this issue when taking a history. Early detection is useful because pseudofolliculitis barbae is more easily resolved in younger women than in older women.

When the problem is resolved, patient satisfaction is very high. For this reason, Dr. Roberts called diagnosis and treatment of pseudofolliculitis barbae “a practice builder.” Based on her approach, “you can really get these ladies clear.”

Dr. Roberts reports financial relationships with an extensive list of companies that market dermatologic and cosmetic products.

NEW YORK – For women with pseudofolliculitis barbae, an empirically-based strategy of microdermabrasion, laser treatment, emollients, and maintenance retinoids has been found highly effective, Wendy Roberts, MD, reported at the Skin of Color Update 2019.

“We didn’t have great treatments for this problem in the past, but the technology has evolved, and you can now get most women clear,” Dr. Roberts, a dermatologist who practices in Rancho Mirage, Calif., said at the meeting.

This approach is appropriate in all women, but Dr. Roberts focused on her experience with black patients, for whom an antioxidant cream is added to address the inflammatory-associated hyperpigmentation that often accompanies pseudofolliculitis barbae, a chronic inflammatory skin condition typically characterized by small, painful papules and pustules.

Start with microdermabrasion to treat the hypertrophic hair follicles and address keratin plugs, Dr. Roberts said. The microdermabrasion smooths the skin and increases penetration of subsequent creams and topics, she said.

“In the same session, I treat with Nd-YAG 1064 nm laser using short pulses,” she noted. For black women, she makes four passes with the laser at a level of moderate intensity. For those with lighter skin, she might perform as many as six passes with the laser set higher.

The microdermabrasion is repeated monthly for three or four treatments, but can be extended for those with persistent symptoms, Dr. Roberts pointed out. She presented a case of a patient who required seven treatments to achieve a satisfactory response.

Patients are instructed to avoid hair plucking and over the course of treatment nightly topical tretinoin is recommended for maintenance. Regular use of emollients is also recommended. For black women who have developed hyperpigmentation as a complication of pseudofolliculitis barbae, Dr. Roberts prescribes a lightening cream.

“I have pretty much moved away from hydroquinone,” said Dr. Roberts, explaining that she has achieved better results with topical cysteamine, a product that she has been using for about 3 years.

In outlining her treatment strategy, she employed case studies of two black women, both of whom achieved resolution of the problem and were satisfied with the results. She said that the same approach is suitable for women of other racial and ethnic groups.

Most commonly seen in black men, pseudofolliculitis barbae – also known as razor bumps – can occur as a complication of shaving in men or women from any racial and ethnic group. However, because of their embarrassment, women often fail to volunteer that they are struggling with this problem. Some women have been afflicted for years and have developed a regular routine of shaving or plucking hairs and then applying makeup for camouflage, Dr. Roberts said.

“This is a patient who rarely presents the problem to the dermatologist. Yet, she is in every one of our practices,” she added. Due to the frequency with which she has identified pseudofolliculitis barbae in patients who are being seen for a different complaint, she now routinely asks patients about this issue when taking a history. Early detection is useful because pseudofolliculitis barbae is more easily resolved in younger women than in older women.

When the problem is resolved, patient satisfaction is very high. For this reason, Dr. Roberts called diagnosis and treatment of pseudofolliculitis barbae “a practice builder.” Based on her approach, “you can really get these ladies clear.”

Dr. Roberts reports financial relationships with an extensive list of companies that market dermatologic and cosmetic products.

NEW YORK – For women with pseudofolliculitis barbae, an empirically-based strategy of microdermabrasion, laser treatment, emollients, and maintenance retinoids has been found highly effective, Wendy Roberts, MD, reported at the Skin of Color Update 2019.

“We didn’t have great treatments for this problem in the past, but the technology has evolved, and you can now get most women clear,” Dr. Roberts, a dermatologist who practices in Rancho Mirage, Calif., said at the meeting.

This approach is appropriate in all women, but Dr. Roberts focused on her experience with black patients, for whom an antioxidant cream is added to address the inflammatory-associated hyperpigmentation that often accompanies pseudofolliculitis barbae, a chronic inflammatory skin condition typically characterized by small, painful papules and pustules.

Start with microdermabrasion to treat the hypertrophic hair follicles and address keratin plugs, Dr. Roberts said. The microdermabrasion smooths the skin and increases penetration of subsequent creams and topics, she said.

“In the same session, I treat with Nd-YAG 1064 nm laser using short pulses,” she noted. For black women, she makes four passes with the laser at a level of moderate intensity. For those with lighter skin, she might perform as many as six passes with the laser set higher.

The microdermabrasion is repeated monthly for three or four treatments, but can be extended for those with persistent symptoms, Dr. Roberts pointed out. She presented a case of a patient who required seven treatments to achieve a satisfactory response.

Patients are instructed to avoid hair plucking and over the course of treatment nightly topical tretinoin is recommended for maintenance. Regular use of emollients is also recommended. For black women who have developed hyperpigmentation as a complication of pseudofolliculitis barbae, Dr. Roberts prescribes a lightening cream.

“I have pretty much moved away from hydroquinone,” said Dr. Roberts, explaining that she has achieved better results with topical cysteamine, a product that she has been using for about 3 years.

In outlining her treatment strategy, she employed case studies of two black women, both of whom achieved resolution of the problem and were satisfied with the results. She said that the same approach is suitable for women of other racial and ethnic groups.

Most commonly seen in black men, pseudofolliculitis barbae – also known as razor bumps – can occur as a complication of shaving in men or women from any racial and ethnic group. However, because of their embarrassment, women often fail to volunteer that they are struggling with this problem. Some women have been afflicted for years and have developed a regular routine of shaving or plucking hairs and then applying makeup for camouflage, Dr. Roberts said.

“This is a patient who rarely presents the problem to the dermatologist. Yet, she is in every one of our practices,” she added. Due to the frequency with which she has identified pseudofolliculitis barbae in patients who are being seen for a different complaint, she now routinely asks patients about this issue when taking a history. Early detection is useful because pseudofolliculitis barbae is more easily resolved in younger women than in older women.

When the problem is resolved, patient satisfaction is very high. For this reason, Dr. Roberts called diagnosis and treatment of pseudofolliculitis barbae “a practice builder.” Based on her approach, “you can really get these ladies clear.”

Dr. Roberts reports financial relationships with an extensive list of companies that market dermatologic and cosmetic products.

NEW YORK – The request for skin lightening agents by nonwhite patients for purely cosmetic purposes is uncomfortable for at least some American dermatologists, judging from an informal survey of those attending the Skin of Color Update 2019, where this topic was introduced.

Ted Bosworth/MDedge News

When the Skin of Color conference chair, Eliot Battle, MD, founder of Cultura Dermatology and Laser Center, Washington, asked who in the audience considered total body whitening to be “wrong,” the show of hands was substantial. He then offered some perspective.

“How many think breast augmentation is wrong?” he asked. “How many think changing your hair color is wrong? Before we cast judgment, let’s think a little about how our patients feel.”

Although he acknowledged the difficulty of separating a racial context from the cultural perception of lighter skin as desirable, Dr. Battle contended that choices regarding appearance are complex. He cautioned against moral judgments blind to this complexity.

“As physicians we need to keep ourselves in check, to keep ourselves from making judgments [regarding lightening agents],” he said.

The two other panelists participating in the same session made compatible observations. Although the other two panelists limited most of their presentations to skin lightening for clinical indications, such as melasma and other disorders of hyperpigmentation, they acknowledged and addressed the sense of discomfort the topic raises.

“To many patients, depigmentation is a passport to society,” said Pearl Grimes, MD, director of the Vitiligo and Pigmentation Institute, Los Angeles. Although she considers this a global issue, not an issue unique to the black population, she counseled dermatologists to “respect the vicissitudes and issues of pigmentation” that she said include the patient’s concerns about beauty, class, and privilege.

Sensitive to the desire of some patients for lighter skin, Cheryl Burgess, MD, founder of the Center for Dermatology and Dermatologic Surgery, Washington, opened her talk by displaying the Time Magazine cover of O.J. Simpson at the time he was accused of murder. The photo appeared to have been intentionally darkened in an effort that was thought by many to make him appear more sinister.

This might be an appropriate example of what skin pigment represents to some segments of American society, but Dr. Battle said that the quest for lighter skin is a global phenomenon. He claims that Asia, India, and Africa are now among the fastest growing and largest markets for skin lightening strategies. The options in those areas of the world, like the United States, are proliferating quickly.

Many of the rapidly expanding options have not yet proved to be effective or safe. The antioxidant glutathione, which is being used for a long list of proven and unproven indications, is among these, according to Dr. Battle. In many clinics where this drug is administered intravenously to avoid degradation in the gastrointestinal tract, he suggested there is reason to believe the staff has little training in safety monitoring.

There are no long-term studies evaluating the safety and efficacy of glutathione for skin lightening, according to Dr. Battle, but there are many case reports of serious toxicities, including death. He listed thyroid dysfunction, renal impairment, and liver dysfunction among adverse events potentially related to glutathione.

“When I gave this talk a year ago, there were no clinics in Washington [offering glutathione]. Now there are seven,” he said.

Even for those dermatologists uncomfortable offering skin lightening for cosmetic purposes, ignoring the demand is ill advised, he said. Evaluating and advising patients on the safety of these agents is one reason to become involved, said Dr. Battle, who noted that specialists in dermatology are uniquely trained to monitor drugs for this application.

“You can tell a patient to stop, but they won’t stop,” said Dr. Battle. He maintained that organized medicine, including the American Academy of Dermatology, should take a role in evaluating the safety and efficacy of lightening agents even when used only for cosmetic indications.

Currently, there are no Food and Drug Administration–approved therapies for whitening of the skin.

“This is such an important question, and I think we need to figure it out,” Dr. Battle said. “Not a day goes by in our practice when we are not asked about skin lightening.”

Dr. Battle reported no relevant disclosures; Dr. Grimes and Dr. Burgess reported multiple financial relationships with industry that are not necessarily relevant to this topic.

NEW YORK – The request for skin lightening agents by nonwhite patients for purely cosmetic purposes is uncomfortable for at least some American dermatologists, judging from an informal survey of those attending the Skin of Color Update 2019, where this topic was introduced.

Ted Bosworth/MDedge News

When the Skin of Color conference chair, Eliot Battle, MD, founder of Cultura Dermatology and Laser Center, Washington, asked who in the audience considered total body whitening to be “wrong,” the show of hands was substantial. He then offered some perspective.

“How many think breast augmentation is wrong?” he asked. “How many think changing your hair color is wrong? Before we cast judgment, let’s think a little about how our patients feel.”

Although he acknowledged the difficulty of separating a racial context from the cultural perception of lighter skin as desirable, Dr. Battle contended that choices regarding appearance are complex. He cautioned against moral judgments blind to this complexity.

“As physicians we need to keep ourselves in check, to keep ourselves from making judgments [regarding lightening agents],” he said.

The two other panelists participating in the same session made compatible observations. Although the other two panelists limited most of their presentations to skin lightening for clinical indications, such as melasma and other disorders of hyperpigmentation, they acknowledged and addressed the sense of discomfort the topic raises.

“To many patients, depigmentation is a passport to society,” said Pearl Grimes, MD, director of the Vitiligo and Pigmentation Institute, Los Angeles. Although she considers this a global issue, not an issue unique to the black population, she counseled dermatologists to “respect the vicissitudes and issues of pigmentation” that she said include the patient’s concerns about beauty, class, and privilege.

Sensitive to the desire of some patients for lighter skin, Cheryl Burgess, MD, founder of the Center for Dermatology and Dermatologic Surgery, Washington, opened her talk by displaying the Time Magazine cover of O.J. Simpson at the time he was accused of murder. The photo appeared to have been intentionally darkened in an effort that was thought by many to make him appear more sinister.

This might be an appropriate example of what skin pigment represents to some segments of American society, but Dr. Battle said that the quest for lighter skin is a global phenomenon. He claims that Asia, India, and Africa are now among the fastest growing and largest markets for skin lightening strategies. The options in those areas of the world, like the United States, are proliferating quickly.

Many of the rapidly expanding options have not yet proved to be effective or safe. The antioxidant glutathione, which is being used for a long list of proven and unproven indications, is among these, according to Dr. Battle. In many clinics where this drug is administered intravenously to avoid degradation in the gastrointestinal tract, he suggested there is reason to believe the staff has little training in safety monitoring.

There are no long-term studies evaluating the safety and efficacy of glutathione for skin lightening, according to Dr. Battle, but there are many case reports of serious toxicities, including death. He listed thyroid dysfunction, renal impairment, and liver dysfunction among adverse events potentially related to glutathione.

“When I gave this talk a year ago, there were no clinics in Washington [offering glutathione]. Now there are seven,” he said.

Even for those dermatologists uncomfortable offering skin lightening for cosmetic purposes, ignoring the demand is ill advised, he said. Evaluating and advising patients on the safety of these agents is one reason to become involved, said Dr. Battle, who noted that specialists in dermatology are uniquely trained to monitor drugs for this application.

“You can tell a patient to stop, but they won’t stop,” said Dr. Battle. He maintained that organized medicine, including the American Academy of Dermatology, should take a role in evaluating the safety and efficacy of lightening agents even when used only for cosmetic indications.

Currently, there are no Food and Drug Administration–approved therapies for whitening of the skin.

“This is such an important question, and I think we need to figure it out,” Dr. Battle said. “Not a day goes by in our practice when we are not asked about skin lightening.”

Dr. Battle reported no relevant disclosures; Dr. Grimes and Dr. Burgess reported multiple financial relationships with industry that are not necessarily relevant to this topic.

NEW YORK – The request for skin lightening agents by nonwhite patients for purely cosmetic purposes is uncomfortable for at least some American dermatologists, judging from an informal survey of those attending the Skin of Color Update 2019, where this topic was introduced.

Ted Bosworth/MDedge News

When the Skin of Color conference chair, Eliot Battle, MD, founder of Cultura Dermatology and Laser Center, Washington, asked who in the audience considered total body whitening to be “wrong,” the show of hands was substantial. He then offered some perspective.

“How many think breast augmentation is wrong?” he asked. “How many think changing your hair color is wrong? Before we cast judgment, let’s think a little about how our patients feel.”

Although he acknowledged the difficulty of separating a racial context from the cultural perception of lighter skin as desirable, Dr. Battle contended that choices regarding appearance are complex. He cautioned against moral judgments blind to this complexity.

“As physicians we need to keep ourselves in check, to keep ourselves from making judgments [regarding lightening agents],” he said.

The two other panelists participating in the same session made compatible observations. Although the other two panelists limited most of their presentations to skin lightening for clinical indications, such as melasma and other disorders of hyperpigmentation, they acknowledged and addressed the sense of discomfort the topic raises.

“To many patients, depigmentation is a passport to society,” said Pearl Grimes, MD, director of the Vitiligo and Pigmentation Institute, Los Angeles. Although she considers this a global issue, not an issue unique to the black population, she counseled dermatologists to “respect the vicissitudes and issues of pigmentation” that she said include the patient’s concerns about beauty, class, and privilege.

Sensitive to the desire of some patients for lighter skin, Cheryl Burgess, MD, founder of the Center for Dermatology and Dermatologic Surgery, Washington, opened her talk by displaying the Time Magazine cover of O.J. Simpson at the time he was accused of murder. The photo appeared to have been intentionally darkened in an effort that was thought by many to make him appear more sinister.

This might be an appropriate example of what skin pigment represents to some segments of American society, but Dr. Battle said that the quest for lighter skin is a global phenomenon. He claims that Asia, India, and Africa are now among the fastest growing and largest markets for skin lightening strategies. The options in those areas of the world, like the United States, are proliferating quickly.

Many of the rapidly expanding options have not yet proved to be effective or safe. The antioxidant glutathione, which is being used for a long list of proven and unproven indications, is among these, according to Dr. Battle. In many clinics where this drug is administered intravenously to avoid degradation in the gastrointestinal tract, he suggested there is reason to believe the staff has little training in safety monitoring.

There are no long-term studies evaluating the safety and efficacy of glutathione for skin lightening, according to Dr. Battle, but there are many case reports of serious toxicities, including death. He listed thyroid dysfunction, renal impairment, and liver dysfunction among adverse events potentially related to glutathione.

“When I gave this talk a year ago, there were no clinics in Washington [offering glutathione]. Now there are seven,” he said.

Even for those dermatologists uncomfortable offering skin lightening for cosmetic purposes, ignoring the demand is ill advised, he said. Evaluating and advising patients on the safety of these agents is one reason to become involved, said Dr. Battle, who noted that specialists in dermatology are uniquely trained to monitor drugs for this application.

“You can tell a patient to stop, but they won’t stop,” said Dr. Battle. He maintained that organized medicine, including the American Academy of Dermatology, should take a role in evaluating the safety and efficacy of lightening agents even when used only for cosmetic indications.

Currently, there are no Food and Drug Administration–approved therapies for whitening of the skin.

“This is such an important question, and I think we need to figure it out,” Dr. Battle said. “Not a day goes by in our practice when we are not asked about skin lightening.”

Dr. Battle reported no relevant disclosures; Dr. Grimes and Dr. Burgess reported multiple financial relationships with industry that are not necessarily relevant to this topic.

MADRID –  In the context of three previous trials, a new phase 3 trial demonstrates that the efficacy of as-needed inhaled corticosteroids (ICS) plus a long-acting beta agonist (LABA) is at least comparable to  maintenance ICS for preventing severe exacerbations in the routine care of patients with mild to moderate asthma, according to a presentation at the 2019 ERS International Congress.

Ted Bosworth/MDedge News

This “real-world” study, called PRACTICAL, produced results similar to those of the previous three studies. It showed similar or modestly improved efficacy for the as-needed approach in patients enrolled with mild to moderate asthma, according to Joanna Hardy, MD, a research fellow at the Medical Research Institute of New Zealand, Wellington.

Currently, the Global Initiative for Asthma (GINA) guidelines identify either of the two strategies tested in this trial as acceptable for patients eligible for step 2 asthma control. This study, as in the three trials published previously, provided reassurance that an as-needed approach is adequate for patients insufficiently adherent to daily maintenance therapy.

In PRACTICAL, the results of which were published just prior to the 2019 ERS Congress (Lancet 2019;394:919-28), 890 patients were randomized to use of a single inhaler containing 200 mcg budesonide plus 6 mcg formoterol as needed for symptoms or to a maintenance regimen with the same dose of budesonide taken twice daily. The protocol allowed 250 mcg terbutaline as needed for symptom control in the maintenance arm. The patients were followed for 52 weeks.

For the primary endpoint of the per-patient number of severe exacerbations, defined as need for 3 consecutive days of oral corticosteroids or an emergency department visit to receive oral corticosteroids, the as-needed approach reduced the relative risk by 31% (hazard ratio, 0.69; P = .049). The per-patient rates of exacerbations for the as-needed and maintenance arms were 0.0119 and 0.172, respectively.

The time to first exacerbation, a secondary endpoint, approached significance in favor of as-needed treatment (HR 0.6; P = .05). There was no difference in asthma control as measured with the Asthma Control Questionnaire or in lung function as measured with forced expiratory volume in 1 second (FEV₁₎ at any visit or at the end of the study.

Two SYGMA trials (SYGMA 1 and SYGMA 2), both published in the New England Journal of Medicine in 2018, addressed the same question. Most like PRACTICAL, SYGMA 2 randomized 4,215 patients with mild asthma and found as-needed budesonide/formoterol noninferior to budesonide maintenance for preventing severe exacerbations.

In SYGMA 1, which included an as-needed terbutaline arm, 3,849 patients were randomized. Although as-needed budesonide-formoterol was inferior to budesonide maintenance in that study (but superior to as-needed to terbutaline), the adherence to budesonide maintenance was 78.9%, which Dr. Hardy said does not reflect real-world patient behavior.

“The problem is that we have a lot of data to show that adherence to maintenance asthma therapy in mild asthma is poor,” Dr. Hardy said. In PRACTICAL, all patients were provided with an asthma action plan but no strategies were offered to improve compliance over those employed in usual practice.

In the open-label Novel START trial, published in 2019 in the New England Journal of Medicine, the question posed was different. In that study, which randomized 675 patients, as-needed budesonide/formoterol was superior to as-needed albuterol for prevention of asthma exacerbations at 52 weeks, the time point employed in all four studies. The results, while confirming the importance of the ICS component, have been generally interpreted as supporting the as-needed therapy in mild asthma.

At the ERS 2019 Congress, one of the moderators of the session in which Dr. Hardy spoke, Guy Brusselle, MD, Ghent (Belgium) University, agreed that the available evidence supports as-needed therapy as a viable strategy in mild asthma, but expressed concern about applying this conclusion to patients who have asthma requiring therapy beyond GINA step 2.

“These data might put patients who need GINA step 3 or 4 therapy at risk of not receiving the maintenance therapy they need for disease control,” Dr. Brusselle said.

In light of the challenge of separating those with moderate from mild asthma, Dr. Brusselle suggested another arm to add to real-world clinical trials attempting to identify the most effective approach.

“The optimal arm might be maintenance budesonide with as-needed ICS/LABA,” Dr. Brusselle said. He explained that even if compliance is low, at least some patients will be receiving a maintenance therapy, and this approach might ultimately offer more benefit than one in which patients do not even consider maintenance.

Dr. Hardy reports no potential conflicts of interest.

MADRID –  In the context of three previous trials, a new phase 3 trial demonstrates that the efficacy of as-needed inhaled corticosteroids (ICS) plus a long-acting beta agonist (LABA) is at least comparable to  maintenance ICS for preventing severe exacerbations in the routine care of patients with mild to moderate asthma, according to a presentation at the 2019 ERS International Congress.

Ted Bosworth/MDedge News

This “real-world” study, called PRACTICAL, produced results similar to those of the previous three studies. It showed similar or modestly improved efficacy for the as-needed approach in patients enrolled with mild to moderate asthma, according to Joanna Hardy, MD, a research fellow at the Medical Research Institute of New Zealand, Wellington.

Currently, the Global Initiative for Asthma (GINA) guidelines identify either of the two strategies tested in this trial as acceptable for patients eligible for step 2 asthma control. This study, as in the three trials published previously, provided reassurance that an as-needed approach is adequate for patients insufficiently adherent to daily maintenance therapy.

In PRACTICAL, the results of which were published just prior to the 2019 ERS Congress (Lancet 2019;394:919-28), 890 patients were randomized to use of a single inhaler containing 200 mcg budesonide plus 6 mcg formoterol as needed for symptoms or to a maintenance regimen with the same dose of budesonide taken twice daily. The protocol allowed 250 mcg terbutaline as needed for symptom control in the maintenance arm. The patients were followed for 52 weeks.

For the primary endpoint of the per-patient number of severe exacerbations, defined as need for 3 consecutive days of oral corticosteroids or an emergency department visit to receive oral corticosteroids, the as-needed approach reduced the relative risk by 31% (hazard ratio, 0.69; P = .049). The per-patient rates of exacerbations for the as-needed and maintenance arms were 0.0119 and 0.172, respectively.

The time to first exacerbation, a secondary endpoint, approached significance in favor of as-needed treatment (HR 0.6; P = .05). There was no difference in asthma control as measured with the Asthma Control Questionnaire or in lung function as measured with forced expiratory volume in 1 second (FEV₁₎ at any visit or at the end of the study.

Two SYGMA trials (SYGMA 1 and SYGMA 2), both published in the New England Journal of Medicine in 2018, addressed the same question. Most like PRACTICAL, SYGMA 2 randomized 4,215 patients with mild asthma and found as-needed budesonide/formoterol noninferior to budesonide maintenance for preventing severe exacerbations.

In SYGMA 1, which included an as-needed terbutaline arm, 3,849 patients were randomized. Although as-needed budesonide-formoterol was inferior to budesonide maintenance in that study (but superior to as-needed to terbutaline), the adherence to budesonide maintenance was 78.9%, which Dr. Hardy said does not reflect real-world patient behavior.

“The problem is that we have a lot of data to show that adherence to maintenance asthma therapy in mild asthma is poor,” Dr. Hardy said. In PRACTICAL, all patients were provided with an asthma action plan but no strategies were offered to improve compliance over those employed in usual practice.

In the open-label Novel START trial, published in 2019 in the New England Journal of Medicine, the question posed was different. In that study, which randomized 675 patients, as-needed budesonide/formoterol was superior to as-needed albuterol for prevention of asthma exacerbations at 52 weeks, the time point employed in all four studies. The results, while confirming the importance of the ICS component, have been generally interpreted as supporting the as-needed therapy in mild asthma.

At the ERS 2019 Congress, one of the moderators of the session in which Dr. Hardy spoke, Guy Brusselle, MD, Ghent (Belgium) University, agreed that the available evidence supports as-needed therapy as a viable strategy in mild asthma, but expressed concern about applying this conclusion to patients who have asthma requiring therapy beyond GINA step 2.

“These data might put patients who need GINA step 3 or 4 therapy at risk of not receiving the maintenance therapy they need for disease control,” Dr. Brusselle said.

In light of the challenge of separating those with moderate from mild asthma, Dr. Brusselle suggested another arm to add to real-world clinical trials attempting to identify the most effective approach.

“The optimal arm might be maintenance budesonide with as-needed ICS/LABA,” Dr. Brusselle said. He explained that even if compliance is low, at least some patients will be receiving a maintenance therapy, and this approach might ultimately offer more benefit than one in which patients do not even consider maintenance.

Dr. Hardy reports no potential conflicts of interest.

MADRID –  In the context of three previous trials, a new phase 3 trial demonstrates that the efficacy of as-needed inhaled corticosteroids (ICS) plus a long-acting beta agonist (LABA) is at least comparable to  maintenance ICS for preventing severe exacerbations in the routine care of patients with mild to moderate asthma, according to a presentation at the 2019 ERS International Congress.

Ted Bosworth/MDedge News

This “real-world” study, called PRACTICAL, produced results similar to those of the previous three studies. It showed similar or modestly improved efficacy for the as-needed approach in patients enrolled with mild to moderate asthma, according to Joanna Hardy, MD, a research fellow at the Medical Research Institute of New Zealand, Wellington.

Currently, the Global Initiative for Asthma (GINA) guidelines identify either of the two strategies tested in this trial as acceptable for patients eligible for step 2 asthma control. This study, as in the three trials published previously, provided reassurance that an as-needed approach is adequate for patients insufficiently adherent to daily maintenance therapy.

In PRACTICAL, the results of which were published just prior to the 2019 ERS Congress (Lancet 2019;394:919-28), 890 patients were randomized to use of a single inhaler containing 200 mcg budesonide plus 6 mcg formoterol as needed for symptoms or to a maintenance regimen with the same dose of budesonide taken twice daily. The protocol allowed 250 mcg terbutaline as needed for symptom control in the maintenance arm. The patients were followed for 52 weeks.

For the primary endpoint of the per-patient number of severe exacerbations, defined as need for 3 consecutive days of oral corticosteroids or an emergency department visit to receive oral corticosteroids, the as-needed approach reduced the relative risk by 31% (hazard ratio, 0.69; P = .049). The per-patient rates of exacerbations for the as-needed and maintenance arms were 0.0119 and 0.172, respectively.

The time to first exacerbation, a secondary endpoint, approached significance in favor of as-needed treatment (HR 0.6; P = .05). There was no difference in asthma control as measured with the Asthma Control Questionnaire or in lung function as measured with forced expiratory volume in 1 second (FEV₁₎ at any visit or at the end of the study.

Two SYGMA trials (SYGMA 1 and SYGMA 2), both published in the New England Journal of Medicine in 2018, addressed the same question. Most like PRACTICAL, SYGMA 2 randomized 4,215 patients with mild asthma and found as-needed budesonide/formoterol noninferior to budesonide maintenance for preventing severe exacerbations.

In SYGMA 1, which included an as-needed terbutaline arm, 3,849 patients were randomized. Although as-needed budesonide-formoterol was inferior to budesonide maintenance in that study (but superior to as-needed to terbutaline), the adherence to budesonide maintenance was 78.9%, which Dr. Hardy said does not reflect real-world patient behavior.

“The problem is that we have a lot of data to show that adherence to maintenance asthma therapy in mild asthma is poor,” Dr. Hardy said. In PRACTICAL, all patients were provided with an asthma action plan but no strategies were offered to improve compliance over those employed in usual practice.

In the open-label Novel START trial, published in 2019 in the New England Journal of Medicine, the question posed was different. In that study, which randomized 675 patients, as-needed budesonide/formoterol was superior to as-needed albuterol for prevention of asthma exacerbations at 52 weeks, the time point employed in all four studies. The results, while confirming the importance of the ICS component, have been generally interpreted as supporting the as-needed therapy in mild asthma.

At the ERS 2019 Congress, one of the moderators of the session in which Dr. Hardy spoke, Guy Brusselle, MD, Ghent (Belgium) University, agreed that the available evidence supports as-needed therapy as a viable strategy in mild asthma, but expressed concern about applying this conclusion to patients who have asthma requiring therapy beyond GINA step 2.

“These data might put patients who need GINA step 3 or 4 therapy at risk of not receiving the maintenance therapy they need for disease control,” Dr. Brusselle said.

In light of the challenge of separating those with moderate from mild asthma, Dr. Brusselle suggested another arm to add to real-world clinical trials attempting to identify the most effective approach.

“The optimal arm might be maintenance budesonide with as-needed ICS/LABA,” Dr. Brusselle said. He explained that even if compliance is low, at least some patients will be receiving a maintenance therapy, and this approach might ultimately offer more benefit than one in which patients do not even consider maintenance.

Dr. Hardy reports no potential conflicts of interest.

MADRID – The serious adverse events faced by asthma patients taking maintenance or rescue oral corticosteroids (OCS) might be avoidable if data from a Dutch study presented at the annual congress of the European Respiratory Society are representative of practice elsewhere.

“The main message from our study is that OCS overuse is common and unnecessary in the majority of asthma patients,” reported Katrien A.B. Eger, MD, Amsterdam University Medical Centre.

In this study, 5,002 patients on high doses of inhaled corticosteroids (ICS), defined as at least 500 mcg/day, were identified in a pharmacy database in the Netherlands. These patients were asked to complete a questionnaire to determine how many had severe asthma and had received rescue or maintenance OCS in the past year.

Drawing from the pharmacy database, it could be determined that 29% of the 2,312 patients who responded to the questionnaire were taking harmfully high doses of OCS as well as high doses of ICS. For this study, harmful exposure was defined as a cumulative intake of 420 mg of prednisone-equivalent OCS over a 1-year period. The median cumulative 1-year exposure, according to Dr. Eger, was 750 mg of prednisone equivalent.

In this population, the investigators then calculated ICS medication adherence based on prescription refills. In addition, a subset of this population was evaluated for inhaler technique.

On the basis of these calculations, 47.4% of patients with harmful OCS exposure were found not to be adherent to their prescribed ICS. Of those who were adherent, 53.9% were found not be taking their inhaled steroids appropriately,

When these numbers are put together, the data suggest “78.1% of high OCS users are either nonadherent or using poor inhalation techniques, which means there is a big potential for treatment optimization,” Dr. Eger said.

Yet even among the 21.9% who were adherent and using good inhaler technique, identifying a group who presumably require OCS for exacerbations, the study found that only 46.1% had been prescribed a biologic, which Dr. Eger considers an important steroid-sparing option. She conceded that many of those not on a biologic might not be candidates, but she believes this is another missed opportunity for reducing OCS exposure.

“In the Netherlands, we have very good access to health care, and biologics are available to anyone who needs them,” said Dr. Eger, explaining that access to these drugs is not a barrier.

The evidence overall is that not enough is being done to ensure that asthma patients are being protected from the risks of OCS, according to Dr. Eger. Citing evidence that adverse events associated with OCS begin with a cumulative lifetime prednisone-equivalent exposure of only 500 mg, she believes that clinicians should be more aggressive in intervening.

“We know that there are both acute and chronic complications associated with OCS that involve a range of organ systems,” Dr. Eger said. She listed osteoporosis, diabetes mellitus, hypertension, and adrenal insufficiency as examples. Rescue OCS, even if used sparingly, can drive risk of OCS complications attributable to the importance of cumulative exposure.

In the session where these data were presented, the moderator, Guy Brusselle, MD, professor of asthma and immunology, Ghent (Belgium) University, labeled them “important.” However, he quibbled with Dr. Eger’s assertion that biologics represent a major opportunity to reduce OCS exposure.

“By suggesting that biologics are not being used often enough, there is an assumption that all of these patients have type 2 inflammatory asthma,” Dr. Brusselle said. “I think it makes more sense to emphasize steroid-sparing strategies, not just biologics.”

Dr. Eger did not disagree, but she emphasized that steroid-sparing alternatives are just one strategy to reduce OCS exposure, and ensuring that patients are adherent to prescribed ICS therapies and are using them correctly might have an even greater impact.

Dr. Eger reports no potential conflicts of interest.

MADRID – The serious adverse events faced by asthma patients taking maintenance or rescue oral corticosteroids (OCS) might be avoidable if data from a Dutch study presented at the annual congress of the European Respiratory Society are representative of practice elsewhere.

“The main message from our study is that OCS overuse is common and unnecessary in the majority of asthma patients,” reported Katrien A.B. Eger, MD, Amsterdam University Medical Centre.

In this study, 5,002 patients on high doses of inhaled corticosteroids (ICS), defined as at least 500 mcg/day, were identified in a pharmacy database in the Netherlands. These patients were asked to complete a questionnaire to determine how many had severe asthma and had received rescue or maintenance OCS in the past year.

Drawing from the pharmacy database, it could be determined that 29% of the 2,312 patients who responded to the questionnaire were taking harmfully high doses of OCS as well as high doses of ICS. For this study, harmful exposure was defined as a cumulative intake of 420 mg of prednisone-equivalent OCS over a 1-year period. The median cumulative 1-year exposure, according to Dr. Eger, was 750 mg of prednisone equivalent.

In this population, the investigators then calculated ICS medication adherence based on prescription refills. In addition, a subset of this population was evaluated for inhaler technique.

On the basis of these calculations, 47.4% of patients with harmful OCS exposure were found not to be adherent to their prescribed ICS. Of those who were adherent, 53.9% were found not be taking their inhaled steroids appropriately,

When these numbers are put together, the data suggest “78.1% of high OCS users are either nonadherent or using poor inhalation techniques, which means there is a big potential for treatment optimization,” Dr. Eger said.

Yet even among the 21.9% who were adherent and using good inhaler technique, identifying a group who presumably require OCS for exacerbations, the study found that only 46.1% had been prescribed a biologic, which Dr. Eger considers an important steroid-sparing option. She conceded that many of those not on a biologic might not be candidates, but she believes this is another missed opportunity for reducing OCS exposure.

“In the Netherlands, we have very good access to health care, and biologics are available to anyone who needs them,” said Dr. Eger, explaining that access to these drugs is not a barrier.

The evidence overall is that not enough is being done to ensure that asthma patients are being protected from the risks of OCS, according to Dr. Eger. Citing evidence that adverse events associated with OCS begin with a cumulative lifetime prednisone-equivalent exposure of only 500 mg, she believes that clinicians should be more aggressive in intervening.

“We know that there are both acute and chronic complications associated with OCS that involve a range of organ systems,” Dr. Eger said. She listed osteoporosis, diabetes mellitus, hypertension, and adrenal insufficiency as examples. Rescue OCS, even if used sparingly, can drive risk of OCS complications attributable to the importance of cumulative exposure.

In the session where these data were presented, the moderator, Guy Brusselle, MD, professor of asthma and immunology, Ghent (Belgium) University, labeled them “important.” However, he quibbled with Dr. Eger’s assertion that biologics represent a major opportunity to reduce OCS exposure.

“By suggesting that biologics are not being used often enough, there is an assumption that all of these patients have type 2 inflammatory asthma,” Dr. Brusselle said. “I think it makes more sense to emphasize steroid-sparing strategies, not just biologics.”

Dr. Eger did not disagree, but she emphasized that steroid-sparing alternatives are just one strategy to reduce OCS exposure, and ensuring that patients are adherent to prescribed ICS therapies and are using them correctly might have an even greater impact.

Dr. Eger reports no potential conflicts of interest.

MADRID – The serious adverse events faced by asthma patients taking maintenance or rescue oral corticosteroids (OCS) might be avoidable if data from a Dutch study presented at the annual congress of the European Respiratory Society are representative of practice elsewhere.

“The main message from our study is that OCS overuse is common and unnecessary in the majority of asthma patients,” reported Katrien A.B. Eger, MD, Amsterdam University Medical Centre.

In this study, 5,002 patients on high doses of inhaled corticosteroids (ICS), defined as at least 500 mcg/day, were identified in a pharmacy database in the Netherlands. These patients were asked to complete a questionnaire to determine how many had severe asthma and had received rescue or maintenance OCS in the past year.

Drawing from the pharmacy database, it could be determined that 29% of the 2,312 patients who responded to the questionnaire were taking harmfully high doses of OCS as well as high doses of ICS. For this study, harmful exposure was defined as a cumulative intake of 420 mg of prednisone-equivalent OCS over a 1-year period. The median cumulative 1-year exposure, according to Dr. Eger, was 750 mg of prednisone equivalent.

In this population, the investigators then calculated ICS medication adherence based on prescription refills. In addition, a subset of this population was evaluated for inhaler technique.

On the basis of these calculations, 47.4% of patients with harmful OCS exposure were found not to be adherent to their prescribed ICS. Of those who were adherent, 53.9% were found not be taking their inhaled steroids appropriately,

When these numbers are put together, the data suggest “78.1% of high OCS users are either nonadherent or using poor inhalation techniques, which means there is a big potential for treatment optimization,” Dr. Eger said.

Yet even among the 21.9% who were adherent and using good inhaler technique, identifying a group who presumably require OCS for exacerbations, the study found that only 46.1% had been prescribed a biologic, which Dr. Eger considers an important steroid-sparing option. She conceded that many of those not on a biologic might not be candidates, but she believes this is another missed opportunity for reducing OCS exposure.

“In the Netherlands, we have very good access to health care, and biologics are available to anyone who needs them,” said Dr. Eger, explaining that access to these drugs is not a barrier.

The evidence overall is that not enough is being done to ensure that asthma patients are being protected from the risks of OCS, according to Dr. Eger. Citing evidence that adverse events associated with OCS begin with a cumulative lifetime prednisone-equivalent exposure of only 500 mg, she believes that clinicians should be more aggressive in intervening.

“We know that there are both acute and chronic complications associated with OCS that involve a range of organ systems,” Dr. Eger said. She listed osteoporosis, diabetes mellitus, hypertension, and adrenal insufficiency as examples. Rescue OCS, even if used sparingly, can drive risk of OCS complications attributable to the importance of cumulative exposure.

In the session where these data were presented, the moderator, Guy Brusselle, MD, professor of asthma and immunology, Ghent (Belgium) University, labeled them “important.” However, he quibbled with Dr. Eger’s assertion that biologics represent a major opportunity to reduce OCS exposure.

“By suggesting that biologics are not being used often enough, there is an assumption that all of these patients have type 2 inflammatory asthma,” Dr. Brusselle said. “I think it makes more sense to emphasize steroid-sparing strategies, not just biologics.”

Dr. Eger did not disagree, but she emphasized that steroid-sparing alternatives are just one strategy to reduce OCS exposure, and ensuring that patients are adherent to prescribed ICS therapies and are using them correctly might have an even greater impact.

Dr. Eger reports no potential conflicts of interest.

NEW YORK – For unclear reasons, the prevalence of central centrifugal cicatricial alopecia (CCCA), a progressive disease of permanent hair loss, is increasing dramatically among black women, creating an urgent need for early diagnosis and treatment, according to an expert who described this phenomenon at the Skin of Color Update 2019.

Ted Bosworth/MDedge News

“CCCA has reached epidemic proportions,” contended Susan Taylor, MD, director of diversity, department of dermatology, Penn Medicine, Philadelphia.

Published data place prevalence rates of CCCA somewhere in the range of 3% to 6% among black women, but Dr. Taylor reported that she believes the condition is underdiagnosed. “I am seeing far more patients now than I was 30 years ago,” she maintained.

Others participating in the Skin of Color Update 2019 agreed. Heather Woolery-Lloyd, MD, director of ethnic skin care, department of dermatology and cutaneous surgery, University of Miami, also called the rising incidence of CCCA “an epidemic.” She, like Dr. Taylor, emphasized the critical importance of early diagnosis and treatment.

“I tell patients that if we can prevent hair loss over the next 10 years, this is a treatment success,” Dr. Woolery-Lloyd said. Although hair regrowth can be achieved in a minority of patients with treatments such as minoxidil, “the first goal is to prevent hair loss.”

Upon diagnosis, Dr. Woolery-Lloyd recommends treatment with intralesional triamcinolone and topical steroids immediately, adding other agents, such as oral antibiotics, if needed. Even in cases where CCCA has been identified before hair loss is visible, Dr. Woolery-Lloyd advised immediate therapy. Given that CCCA is a disease of reversible hair loss, she said, “do not take a wait-and-see approach.”

One potential obstacle for early diagnosis of CCCA, shared by other types of alopecia that are common in skin of color, is the failure of many clinicians to employ a standardized diagnosis in this patient population.

“If you do not have tightly coiled hair, it does not mean you cannot understand tightly coiled hair, but you have to learn, and you have to let patients know that you understand and have experience,” said Dr. Taylor, emphasizing the role of reassuring patients so they can be confident in the clinical recommendations.

Part of this reassurance will be derived from “interacting with patients in a culturally competent manner,” Dr. Taylor said. Clinicians must develop comfort and confidence in physically examining the hair and scalp, in asking patients to remove weaves or braids for a thorough inspection, and in avoiding comments that might be misinterpreted. Among these, she advised tactful questions about shampooing to avoid any implication that the clinician is implying inadequate hygiene.

When CCCA is suspected, a “biopsy is important” even in circumstances when the diagnosis seems straightforward. For one reason, a substantial proportion of patients may have a concomitant diagnosis. Dr. Taylor cited data from one study in which nearly 20% of CCCA patients also had traction alopecia and more than 10% had androgenic alopecia. Other coexisting problems identified on biopsy, including infection or seborrheic dermatitis, can help clinicians tailor a more effective intervention.

The initial signs of CCCA are typically hair breakage in the vertex of the scalp, which then expands in a central centrifugal pattern, according to Dr. Taylor. Although not all patients have signs of inflammation, such as itching and pustules, inhibition of inflammation represents the first line of therapy.

Relative to hair in the white population, the hair of black individuals grows more slowly and is more fragile, with greater amounts of breakage, said Dr. Taylor, citing published studies that support these differences. To improve early diagnosis of CCCA, understanding the hair in the black population is the first step for spotting problems in routine physical examinations. It may be this lack of familiarity that is contributing to underdiagnosis of CCCA.

“Almost 70% of African-American patients feel that physicians do not understand their hair,” Dr. Taylor said. “Let’s begin to change that.”

Cautioning that it is too often assumed that hairstyles and hair care, such as relaxants or hot combs, are the source of hair loss in black women, Dr. Taylor advised not to jump to conclusions. As an example, she described a case where weaves, braids, and other strategies were employed to mask alopecia after CCCA developed, not before.

“CCCA is the most important cause of scarring alopecia in African-American women,” Dr. Taylor said. Reiterating that hair loss can be prevented or modified with treatment, she added that this places the emphasis on first obtaining an accurate diagnosis.

Dr. Taylor has a financial relationship with Biersdorf; Dr. Woolery-Lloyd has financial relationships with Allergan, Galderma, Ortho Diagnostics, Pfizer, and Somabella Laboratories.

NEW YORK – For unclear reasons, the prevalence of central centrifugal cicatricial alopecia (CCCA), a progressive disease of permanent hair loss, is increasing dramatically among black women, creating an urgent need for early diagnosis and treatment, according to an expert who described this phenomenon at the Skin of Color Update 2019.

Ted Bosworth/MDedge News

“CCCA has reached epidemic proportions,” contended Susan Taylor, MD, director of diversity, department of dermatology, Penn Medicine, Philadelphia.

Published data place prevalence rates of CCCA somewhere in the range of 3% to 6% among black women, but Dr. Taylor reported that she believes the condition is underdiagnosed. “I am seeing far more patients now than I was 30 years ago,” she maintained.

Others participating in the Skin of Color Update 2019 agreed. Heather Woolery-Lloyd, MD, director of ethnic skin care, department of dermatology and cutaneous surgery, University of Miami, also called the rising incidence of CCCA “an epidemic.” She, like Dr. Taylor, emphasized the critical importance of early diagnosis and treatment.

“I tell patients that if we can prevent hair loss over the next 10 years, this is a treatment success,” Dr. Woolery-Lloyd said. Although hair regrowth can be achieved in a minority of patients with treatments such as minoxidil, “the first goal is to prevent hair loss.”

Upon diagnosis, Dr. Woolery-Lloyd recommends treatment with intralesional triamcinolone and topical steroids immediately, adding other agents, such as oral antibiotics, if needed. Even in cases where CCCA has been identified before hair loss is visible, Dr. Woolery-Lloyd advised immediate therapy. Given that CCCA is a disease of reversible hair loss, she said, “do not take a wait-and-see approach.”

One potential obstacle for early diagnosis of CCCA, shared by other types of alopecia that are common in skin of color, is the failure of many clinicians to employ a standardized diagnosis in this patient population.

“If you do not have tightly coiled hair, it does not mean you cannot understand tightly coiled hair, but you have to learn, and you have to let patients know that you understand and have experience,” said Dr. Taylor, emphasizing the role of reassuring patients so they can be confident in the clinical recommendations.

Part of this reassurance will be derived from “interacting with patients in a culturally competent manner,” Dr. Taylor said. Clinicians must develop comfort and confidence in physically examining the hair and scalp, in asking patients to remove weaves or braids for a thorough inspection, and in avoiding comments that might be misinterpreted. Among these, she advised tactful questions about shampooing to avoid any implication that the clinician is implying inadequate hygiene.

When CCCA is suspected, a “biopsy is important” even in circumstances when the diagnosis seems straightforward. For one reason, a substantial proportion of patients may have a concomitant diagnosis. Dr. Taylor cited data from one study in which nearly 20% of CCCA patients also had traction alopecia and more than 10% had androgenic alopecia. Other coexisting problems identified on biopsy, including infection or seborrheic dermatitis, can help clinicians tailor a more effective intervention.

The initial signs of CCCA are typically hair breakage in the vertex of the scalp, which then expands in a central centrifugal pattern, according to Dr. Taylor. Although not all patients have signs of inflammation, such as itching and pustules, inhibition of inflammation represents the first line of therapy.

Relative to hair in the white population, the hair of black individuals grows more slowly and is more fragile, with greater amounts of breakage, said Dr. Taylor, citing published studies that support these differences. To improve early diagnosis of CCCA, understanding the hair in the black population is the first step for spotting problems in routine physical examinations. It may be this lack of familiarity that is contributing to underdiagnosis of CCCA.

“Almost 70% of African-American patients feel that physicians do not understand their hair,” Dr. Taylor said. “Let’s begin to change that.”

Cautioning that it is too often assumed that hairstyles and hair care, such as relaxants or hot combs, are the source of hair loss in black women, Dr. Taylor advised not to jump to conclusions. As an example, she described a case where weaves, braids, and other strategies were employed to mask alopecia after CCCA developed, not before.

“CCCA is the most important cause of scarring alopecia in African-American women,” Dr. Taylor said. Reiterating that hair loss can be prevented or modified with treatment, she added that this places the emphasis on first obtaining an accurate diagnosis.

Dr. Taylor has a financial relationship with Biersdorf; Dr. Woolery-Lloyd has financial relationships with Allergan, Galderma, Ortho Diagnostics, Pfizer, and Somabella Laboratories.

NEW YORK – For unclear reasons, the prevalence of central centrifugal cicatricial alopecia (CCCA), a progressive disease of permanent hair loss, is increasing dramatically among black women, creating an urgent need for early diagnosis and treatment, according to an expert who described this phenomenon at the Skin of Color Update 2019.

Ted Bosworth/MDedge News

“CCCA has reached epidemic proportions,” contended Susan Taylor, MD, director of diversity, department of dermatology, Penn Medicine, Philadelphia.

Published data place prevalence rates of CCCA somewhere in the range of 3% to 6% among black women, but Dr. Taylor reported that she believes the condition is underdiagnosed. “I am seeing far more patients now than I was 30 years ago,” she maintained.

Others participating in the Skin of Color Update 2019 agreed. Heather Woolery-Lloyd, MD, director of ethnic skin care, department of dermatology and cutaneous surgery, University of Miami, also called the rising incidence of CCCA “an epidemic.” She, like Dr. Taylor, emphasized the critical importance of early diagnosis and treatment.

“I tell patients that if we can prevent hair loss over the next 10 years, this is a treatment success,” Dr. Woolery-Lloyd said. Although hair regrowth can be achieved in a minority of patients with treatments such as minoxidil, “the first goal is to prevent hair loss.”

Upon diagnosis, Dr. Woolery-Lloyd recommends treatment with intralesional triamcinolone and topical steroids immediately, adding other agents, such as oral antibiotics, if needed. Even in cases where CCCA has been identified before hair loss is visible, Dr. Woolery-Lloyd advised immediate therapy. Given that CCCA is a disease of reversible hair loss, she said, “do not take a wait-and-see approach.”

One potential obstacle for early diagnosis of CCCA, shared by other types of alopecia that are common in skin of color, is the failure of many clinicians to employ a standardized diagnosis in this patient population.

“If you do not have tightly coiled hair, it does not mean you cannot understand tightly coiled hair, but you have to learn, and you have to let patients know that you understand and have experience,” said Dr. Taylor, emphasizing the role of reassuring patients so they can be confident in the clinical recommendations.

Part of this reassurance will be derived from “interacting with patients in a culturally competent manner,” Dr. Taylor said. Clinicians must develop comfort and confidence in physically examining the hair and scalp, in asking patients to remove weaves or braids for a thorough inspection, and in avoiding comments that might be misinterpreted. Among these, she advised tactful questions about shampooing to avoid any implication that the clinician is implying inadequate hygiene.

When CCCA is suspected, a “biopsy is important” even in circumstances when the diagnosis seems straightforward. For one reason, a substantial proportion of patients may have a concomitant diagnosis. Dr. Taylor cited data from one study in which nearly 20% of CCCA patients also had traction alopecia and more than 10% had androgenic alopecia. Other coexisting problems identified on biopsy, including infection or seborrheic dermatitis, can help clinicians tailor a more effective intervention.

The initial signs of CCCA are typically hair breakage in the vertex of the scalp, which then expands in a central centrifugal pattern, according to Dr. Taylor. Although not all patients have signs of inflammation, such as itching and pustules, inhibition of inflammation represents the first line of therapy.

Relative to hair in the white population, the hair of black individuals grows more slowly and is more fragile, with greater amounts of breakage, said Dr. Taylor, citing published studies that support these differences. To improve early diagnosis of CCCA, understanding the hair in the black population is the first step for spotting problems in routine physical examinations. It may be this lack of familiarity that is contributing to underdiagnosis of CCCA.

“Almost 70% of African-American patients feel that physicians do not understand their hair,” Dr. Taylor said. “Let’s begin to change that.”

Cautioning that it is too often assumed that hairstyles and hair care, such as relaxants or hot combs, are the source of hair loss in black women, Dr. Taylor advised not to jump to conclusions. As an example, she described a case where weaves, braids, and other strategies were employed to mask alopecia after CCCA developed, not before.

“CCCA is the most important cause of scarring alopecia in African-American women,” Dr. Taylor said. Reiterating that hair loss can be prevented or modified with treatment, she added that this places the emphasis on first obtaining an accurate diagnosis.

Dr. Taylor has a financial relationship with Biersdorf; Dr. Woolery-Lloyd has financial relationships with Allergan, Galderma, Ortho Diagnostics, Pfizer, and Somabella Laboratories.