Pulmonology

Beyond asthma and chronic obstructive pulmonary disease (COPD), inhalation therapy is a mainstay in the management of bronchiectasis, cystic fibrosis, and pulmonary artery hypertension. Several US Food and Drug Administration off-label indications for inhalational medications include hypoxia secondary to acute respiratory distress syndrome (ARDS) and intraoperative and postoperative pulmonary hypertension during and following cardiac surgery, respectively.^1-11 Therapeutic delivery of aerosols to the lung may be provided via nebulization, pressurized metered-dose inhalers (pMDI), and other devices (eg, dry powder inhalers, soft-mist inhalers, and smart inhalers).¹² The most common aerosolized medications given in the clinical setting are bronchodilators.¹²

Product selection is often guided by practice guidelines (Table 1), consideration of the formulation’s advantages and disadvantages (Table 2), and/or formulary considerations. For example, current guidelines for COPD state that there is no evidence for superiority of nebulized bronchodilator therapy over handheld devices in patients who can use them properly.² Due to equivalence, nebulized formulations are commonly used in hospitals, emergency departments (EDs) and ambulatory clinics based on the drug’s unit cost. In contrast, a pMDI is often more cost-effective for use in ambulatory patients who are administering multiple doses from the same canister.

The World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) recommend droplet and contact precautions for all patients suspected or diagnosed with novel coronavirus-19 (COVID-19).^13,14 Airborne precautions must be applied when performing aerosol-generating medical procedures (AGMPs), including but not limited to, open suctioning of the respiratory tract, intubation, bronchoscopy, and cardiopulmonary resuscitation (CPR). Data from the severe acute respiratory syndrome (SARS-CoV) epidemic suggest that nebulization of medication is also an AGMP.^15-17

Institutions must ensure that their health care workers (HCWs) are wearing appropriate personal protective equipment (PPE) including gloves, long-sleeved gowns, eye protection, and fit-tested particulate respirators (N95 mask) for airborne procedures and are carefully discarding PPE after use.^13,14 Due to severe shortages in available respirators in the US supply chain, the CDC has temporarily modified WHO recommendations. Face masks are now an acceptable alternative to protect HCWs from splashes and sprays from procedures not likely to generate aerosols and for cleaning of rooms, although there is no evidence to support this decision.

Internationally, HCWs are falling ill with COVID-19. Data from Italy and Spain show that about 9% to 13% of these countries’ cases are HCWs.^18,19 Within the US, the Ohio health department reports approximately 16% of cases are HCWs.²⁰ It is possible that 20% of frontline HCWs will become infected.²¹ Evolving laboratory research shows that COVID-19 remains viable in aerosols for up to 3 hours postaerosolization, thus making aerosol transmission plausible.²² Nebulizers convert liquids into aerosols and during dispersal may potentially cause secondary inhalation of fugitive emissions.²³ Since interim CDC infection control guidance is to allow only essential personnel to enter the room of patients with COVID-19, many facilities will rely on their frontline nursing staff to clean and disinfect high-touch surfaces following routine care activities.²⁴

Achieving adequate fomite disinfection following viral aerosolization may pose a significant problem for any patient receiving scheduled doses of nebulized medications. Additionally, for personnel who clean rooms following intermittent drug nebulization while wearing PPE that includes a face mask, protection from aerosolized virus may be inadequate. Subsequently, fugitive emissions from nebulized medications may potentially contribute to both nosocomial COVID-19 transmission and viral infections in the medical staff until proven otherwise by studies conducted outside of the laboratory. Prevention of infection in the medical staff is imperative since federal health care systems cannot sustain a significant loss of its workforce.

Recommendations

We recommend that health care systems stop business as usual and adopt public health recommendations issued by Canadian and Hong Kong health care authorities for the management of suspected or confirmed COVID-19 disease.^25-28 We have further clarified and expanded on these interventions. During viral pandemics, prescribers and health care systems should:

1. Deprescribe nebulized therapies on medical wards and intensive care units as an infection control measure. Also avoid use in any outpatient health care setting (eg, community-based clinics, EDs, triage).
2. Avoid initiation of nebulized unproven therapies (eg, n-acetylcysteine, hypertonic saline).¹
3. Use alternative bronchodilator formulations as appropriate (eg, oral β-2 agonist, recognizing its slower onset) before prescribing nebulized agents to patients who are uncooperative or unable to follow directions needed to use a pMDI with a spacer or have experienced a prior poor response to a pMDI with spacer (eg, OptiChamber Diamond, Philips).^25,27
4.  Limit nebulized drug utilization (eg, bronchodilators, epoprostenol) to patients who are on mechanical ventilation and will receive nebulized therapies via a closed system or to patients housed in negative pressure hospital rooms.²² Use a viral filter (eg, Salter Labs system) to decrease the spread of infection for those receiving epoprostenol via face mask.²⁵
5. Adjust procurement practices (eg, pharmacy, logistics) to address the transition from nebulized drugs to alternatives.
6. Add a safety net to the drug-ordering process by restricting new orders for nebulized therapies to the prior authorization process.²⁷ Apply the exclusion criterion of suspected or definite COVID-19.
7. Add a safety net to environmental service practices. Nursing staff should track patients who received ≥ 1 nebulizations via open (before diagnosis) or closed systems so that staff wear suitable PPE to include a N-95 mask while cleaning the room.

Conclusions

To implement the aggressive infection control guidance promulgated here, we recommend collaboration with infection control, pharmacy service (eg, prior authorization team, clinical pharmacy team, and procurement team), respiratory therapy, pulmonary and other critical care physicians, EDs, CPR committee, and other stakeholders. When making significant transitions in clinical care during a viral pandemic, guidelines must be timely, use imperative wording, and consist of easily identifiable education and/or instructions for the affected frontline staff in order to change attitudes.²⁹ Additionally, when transitioning from nebulized bronchodilators to pMDI, educational in-services should be provided to frontline staff to avoid misconceptions regarding pMDI treatment efficacy and patients’ ability to use their pMDI with spacer.³⁰

Acknowledgments

This material is the result of work supported with resources and the use of facilities at the VA Tennessee Valley Healthcare System in Nashville.

Beyond asthma and chronic obstructive pulmonary disease (COPD), inhalation therapy is a mainstay in the management of bronchiectasis, cystic fibrosis, and pulmonary artery hypertension. Several US Food and Drug Administration off-label indications for inhalational medications include hypoxia secondary to acute respiratory distress syndrome (ARDS) and intraoperative and postoperative pulmonary hypertension during and following cardiac surgery, respectively.^1-11 Therapeutic delivery of aerosols to the lung may be provided via nebulization, pressurized metered-dose inhalers (pMDI), and other devices (eg, dry powder inhalers, soft-mist inhalers, and smart inhalers).¹² The most common aerosolized medications given in the clinical setting are bronchodilators.¹²

Product selection is often guided by practice guidelines (Table 1), consideration of the formulation’s advantages and disadvantages (Table 2), and/or formulary considerations. For example, current guidelines for COPD state that there is no evidence for superiority of nebulized bronchodilator therapy over handheld devices in patients who can use them properly.² Due to equivalence, nebulized formulations are commonly used in hospitals, emergency departments (EDs) and ambulatory clinics based on the drug’s unit cost. In contrast, a pMDI is often more cost-effective for use in ambulatory patients who are administering multiple doses from the same canister.

The World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) recommend droplet and contact precautions for all patients suspected or diagnosed with novel coronavirus-19 (COVID-19).^13,14 Airborne precautions must be applied when performing aerosol-generating medical procedures (AGMPs), including but not limited to, open suctioning of the respiratory tract, intubation, bronchoscopy, and cardiopulmonary resuscitation (CPR). Data from the severe acute respiratory syndrome (SARS-CoV) epidemic suggest that nebulization of medication is also an AGMP.^15-17

Institutions must ensure that their health care workers (HCWs) are wearing appropriate personal protective equipment (PPE) including gloves, long-sleeved gowns, eye protection, and fit-tested particulate respirators (N95 mask) for airborne procedures and are carefully discarding PPE after use.^13,14 Due to severe shortages in available respirators in the US supply chain, the CDC has temporarily modified WHO recommendations. Face masks are now an acceptable alternative to protect HCWs from splashes and sprays from procedures not likely to generate aerosols and for cleaning of rooms, although there is no evidence to support this decision.

Internationally, HCWs are falling ill with COVID-19. Data from Italy and Spain show that about 9% to 13% of these countries’ cases are HCWs.^18,19 Within the US, the Ohio health department reports approximately 16% of cases are HCWs.²⁰ It is possible that 20% of frontline HCWs will become infected.²¹ Evolving laboratory research shows that COVID-19 remains viable in aerosols for up to 3 hours postaerosolization, thus making aerosol transmission plausible.²² Nebulizers convert liquids into aerosols and during dispersal may potentially cause secondary inhalation of fugitive emissions.²³ Since interim CDC infection control guidance is to allow only essential personnel to enter the room of patients with COVID-19, many facilities will rely on their frontline nursing staff to clean and disinfect high-touch surfaces following routine care activities.²⁴

Achieving adequate fomite disinfection following viral aerosolization may pose a significant problem for any patient receiving scheduled doses of nebulized medications. Additionally, for personnel who clean rooms following intermittent drug nebulization while wearing PPE that includes a face mask, protection from aerosolized virus may be inadequate. Subsequently, fugitive emissions from nebulized medications may potentially contribute to both nosocomial COVID-19 transmission and viral infections in the medical staff until proven otherwise by studies conducted outside of the laboratory. Prevention of infection in the medical staff is imperative since federal health care systems cannot sustain a significant loss of its workforce.

Recommendations

We recommend that health care systems stop business as usual and adopt public health recommendations issued by Canadian and Hong Kong health care authorities for the management of suspected or confirmed COVID-19 disease.^25-28 We have further clarified and expanded on these interventions. During viral pandemics, prescribers and health care systems should:

1. Deprescribe nebulized therapies on medical wards and intensive care units as an infection control measure. Also avoid use in any outpatient health care setting (eg, community-based clinics, EDs, triage).
2. Avoid initiation of nebulized unproven therapies (eg, n-acetylcysteine, hypertonic saline).¹
3. Use alternative bronchodilator formulations as appropriate (eg, oral β-2 agonist, recognizing its slower onset) before prescribing nebulized agents to patients who are uncooperative or unable to follow directions needed to use a pMDI with a spacer or have experienced a prior poor response to a pMDI with spacer (eg, OptiChamber Diamond, Philips).^25,27
4.  Limit nebulized drug utilization (eg, bronchodilators, epoprostenol) to patients who are on mechanical ventilation and will receive nebulized therapies via a closed system or to patients housed in negative pressure hospital rooms.²² Use a viral filter (eg, Salter Labs system) to decrease the spread of infection for those receiving epoprostenol via face mask.²⁵
5. Adjust procurement practices (eg, pharmacy, logistics) to address the transition from nebulized drugs to alternatives.
6. Add a safety net to the drug-ordering process by restricting new orders for nebulized therapies to the prior authorization process.²⁷ Apply the exclusion criterion of suspected or definite COVID-19.
7. Add a safety net to environmental service practices. Nursing staff should track patients who received ≥ 1 nebulizations via open (before diagnosis) or closed systems so that staff wear suitable PPE to include a N-95 mask while cleaning the room.

Conclusions

To implement the aggressive infection control guidance promulgated here, we recommend collaboration with infection control, pharmacy service (eg, prior authorization team, clinical pharmacy team, and procurement team), respiratory therapy, pulmonary and other critical care physicians, EDs, CPR committee, and other stakeholders. When making significant transitions in clinical care during a viral pandemic, guidelines must be timely, use imperative wording, and consist of easily identifiable education and/or instructions for the affected frontline staff in order to change attitudes.²⁹ Additionally, when transitioning from nebulized bronchodilators to pMDI, educational in-services should be provided to frontline staff to avoid misconceptions regarding pMDI treatment efficacy and patients’ ability to use their pMDI with spacer.³⁰

Acknowledgments

This material is the result of work supported with resources and the use of facilities at the VA Tennessee Valley Healthcare System in Nashville.

Beyond asthma and chronic obstructive pulmonary disease (COPD), inhalation therapy is a mainstay in the management of bronchiectasis, cystic fibrosis, and pulmonary artery hypertension. Several US Food and Drug Administration off-label indications for inhalational medications include hypoxia secondary to acute respiratory distress syndrome (ARDS) and intraoperative and postoperative pulmonary hypertension during and following cardiac surgery, respectively.^1-11 Therapeutic delivery of aerosols to the lung may be provided via nebulization, pressurized metered-dose inhalers (pMDI), and other devices (eg, dry powder inhalers, soft-mist inhalers, and smart inhalers).¹² The most common aerosolized medications given in the clinical setting are bronchodilators.¹²

Product selection is often guided by practice guidelines (Table 1), consideration of the formulation’s advantages and disadvantages (Table 2), and/or formulary considerations. For example, current guidelines for COPD state that there is no evidence for superiority of nebulized bronchodilator therapy over handheld devices in patients who can use them properly.² Due to equivalence, nebulized formulations are commonly used in hospitals, emergency departments (EDs) and ambulatory clinics based on the drug’s unit cost. In contrast, a pMDI is often more cost-effective for use in ambulatory patients who are administering multiple doses from the same canister.

The World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) recommend droplet and contact precautions for all patients suspected or diagnosed with novel coronavirus-19 (COVID-19).^13,14 Airborne precautions must be applied when performing aerosol-generating medical procedures (AGMPs), including but not limited to, open suctioning of the respiratory tract, intubation, bronchoscopy, and cardiopulmonary resuscitation (CPR). Data from the severe acute respiratory syndrome (SARS-CoV) epidemic suggest that nebulization of medication is also an AGMP.^15-17

Institutions must ensure that their health care workers (HCWs) are wearing appropriate personal protective equipment (PPE) including gloves, long-sleeved gowns, eye protection, and fit-tested particulate respirators (N95 mask) for airborne procedures and are carefully discarding PPE after use.^13,14 Due to severe shortages in available respirators in the US supply chain, the CDC has temporarily modified WHO recommendations. Face masks are now an acceptable alternative to protect HCWs from splashes and sprays from procedures not likely to generate aerosols and for cleaning of rooms, although there is no evidence to support this decision.

Internationally, HCWs are falling ill with COVID-19. Data from Italy and Spain show that about 9% to 13% of these countries’ cases are HCWs.^18,19 Within the US, the Ohio health department reports approximately 16% of cases are HCWs.²⁰ It is possible that 20% of frontline HCWs will become infected.²¹ Evolving laboratory research shows that COVID-19 remains viable in aerosols for up to 3 hours postaerosolization, thus making aerosol transmission plausible.²² Nebulizers convert liquids into aerosols and during dispersal may potentially cause secondary inhalation of fugitive emissions.²³ Since interim CDC infection control guidance is to allow only essential personnel to enter the room of patients with COVID-19, many facilities will rely on their frontline nursing staff to clean and disinfect high-touch surfaces following routine care activities.²⁴

Achieving adequate fomite disinfection following viral aerosolization may pose a significant problem for any patient receiving scheduled doses of nebulized medications. Additionally, for personnel who clean rooms following intermittent drug nebulization while wearing PPE that includes a face mask, protection from aerosolized virus may be inadequate. Subsequently, fugitive emissions from nebulized medications may potentially contribute to both nosocomial COVID-19 transmission and viral infections in the medical staff until proven otherwise by studies conducted outside of the laboratory. Prevention of infection in the medical staff is imperative since federal health care systems cannot sustain a significant loss of its workforce.

Recommendations

We recommend that health care systems stop business as usual and adopt public health recommendations issued by Canadian and Hong Kong health care authorities for the management of suspected or confirmed COVID-19 disease.^25-28 We have further clarified and expanded on these interventions. During viral pandemics, prescribers and health care systems should:

1. Deprescribe nebulized therapies on medical wards and intensive care units as an infection control measure. Also avoid use in any outpatient health care setting (eg, community-based clinics, EDs, triage).
2. Avoid initiation of nebulized unproven therapies (eg, n-acetylcysteine, hypertonic saline).¹
3. Use alternative bronchodilator formulations as appropriate (eg, oral β-2 agonist, recognizing its slower onset) before prescribing nebulized agents to patients who are uncooperative or unable to follow directions needed to use a pMDI with a spacer or have experienced a prior poor response to a pMDI with spacer (eg, OptiChamber Diamond, Philips).^25,27
4.  Limit nebulized drug utilization (eg, bronchodilators, epoprostenol) to patients who are on mechanical ventilation and will receive nebulized therapies via a closed system or to patients housed in negative pressure hospital rooms.²² Use a viral filter (eg, Salter Labs system) to decrease the spread of infection for those receiving epoprostenol via face mask.²⁵
5. Adjust procurement practices (eg, pharmacy, logistics) to address the transition from nebulized drugs to alternatives.
6. Add a safety net to the drug-ordering process by restricting new orders for nebulized therapies to the prior authorization process.²⁷ Apply the exclusion criterion of suspected or definite COVID-19.
7. Add a safety net to environmental service practices. Nursing staff should track patients who received ≥ 1 nebulizations via open (before diagnosis) or closed systems so that staff wear suitable PPE to include a N-95 mask while cleaning the room.

Conclusions

To implement the aggressive infection control guidance promulgated here, we recommend collaboration with infection control, pharmacy service (eg, prior authorization team, clinical pharmacy team, and procurement team), respiratory therapy, pulmonary and other critical care physicians, EDs, CPR committee, and other stakeholders. When making significant transitions in clinical care during a viral pandemic, guidelines must be timely, use imperative wording, and consist of easily identifiable education and/or instructions for the affected frontline staff in order to change attitudes.²⁹ Additionally, when transitioning from nebulized bronchodilators to pMDI, educational in-services should be provided to frontline staff to avoid misconceptions regarding pMDI treatment efficacy and patients’ ability to use their pMDI with spacer.³⁰

Acknowledgments

This material is the result of work supported with resources and the use of facilities at the VA Tennessee Valley Healthcare System in Nashville.

As clinicians grapple with the COVID-19 pandemic, the American Academy of Pediatrics has released interim guidance on managing infants born of infected mothers.

CDC/ Dr. Fred Murphy; Sylvia Whitfield

“Pediatric cases of COVID-19 are so far reported as less severe than disease occurring among older individuals,” Karen M. Puopolo, MD, PhD, a neonatologist and chief of the section on newborn pediatrics at Pennsylvania Hospital, Philadelphia, and coauthors wrote in the 18-page document, which was released on April 2, 2020, along with an abbreviated “Frequently Asked Questions” summary. However, one study of children with COVID-19 in China found that 12% of confirmed cases occurred among 731 infants aged less than 1 year; 24% of those 86 infants “suffered severe or critical illness” (Pediatrics. 2020 March. doi: 10.1542/peds.2020-0702). There were no deaths reported among these infants. Other case reports have documented COVID-19 in children aged as young as 2 days.

The document, which was assembled by members of the AAP Committee on Fetus and Newborn, Section on Neonatal Perinatal Medicine, and Committee on Infectious Diseases, pointed out that “considerable uncertainty” exists about the possibility for vertical transmission of SARS-CoV-2 from infected pregnant women to their newborns. “Evidence-based guidelines for managing antenatal, intrapartum, and neonatal care around COVID-19 would require an understanding of whether the virus can be transmitted transplacentally; a determination of which maternal body fluids may be infectious; and data of adequate statistical power that describe which maternal, intrapartum, and neonatal factors influence perinatal transmission,” according to the document. “In the midst of the pandemic these data do not exist, with only limited information currently available to address these issues.”

Based on the best available evidence, the guidance authors recommend that clinicians temporarily separate newborns from affected mothers to minimize the risk of postnatal infant infection from maternal respiratory secretions. “Newborns should be bathed as soon as reasonably possible after birth to remove virus potentially present on skin surfaces,” they wrote. “Clinical staff should use airborne, droplet, and contact precautions until newborn virologic status is known to be negative by SARS-CoV-2 [polymerase chain reaction] testing.”

While SARS-CoV-2 has not been detected in breast milk to date, the authors noted that mothers with COVID-19 can express breast milk to be fed to their infants by uninfected caregivers until specific maternal criteria are met. In addition, infants born to mothers with COVID-19 should be tested for SARS-CoV-2 at 24 hours and, if still in the birth facility, at 48 hours after birth. Centers with limited resources for testing may make individual risk/benefit decisions regarding testing.

For infants infected with SARS-CoV-2 but have no symptoms of the disease, they “may be discharged home on a case-by-case basis with appropriate precautions and plans for frequent outpatient follow-up contacts (either by phone, telemedicine, or in office) through 14 days after birth,” according to the document.

If both infant and mother are discharged from the hospital and the mother still has COVID-19 symptoms, she should maintain at least 6 feet of distance from the baby; if she is in closer proximity she should use a mask and hand hygiene. The mother can stop such precautions until she is afebrile without the use of antipyretics for at least 72 hours, and it is at least 7 days since her symptoms first occurred.

In cases where infants require ongoing neonatal intensive care, mothers infected with COVID-19 should not visit their newborn until she is afebrile without the use of antipyretics for at least 72 hours, her respiratory symptoms are improved, and she has negative results of a molecular assay for detection of SARS-CoV-2 from at least two consecutive nasopharyngeal swab specimens collected at least 24 hours apart.

[email protected]
 

As clinicians grapple with the COVID-19 pandemic, the American Academy of Pediatrics has released interim guidance on managing infants born of infected mothers.

CDC/ Dr. Fred Murphy; Sylvia Whitfield

“Pediatric cases of COVID-19 are so far reported as less severe than disease occurring among older individuals,” Karen M. Puopolo, MD, PhD, a neonatologist and chief of the section on newborn pediatrics at Pennsylvania Hospital, Philadelphia, and coauthors wrote in the 18-page document, which was released on April 2, 2020, along with an abbreviated “Frequently Asked Questions” summary. However, one study of children with COVID-19 in China found that 12% of confirmed cases occurred among 731 infants aged less than 1 year; 24% of those 86 infants “suffered severe or critical illness” (Pediatrics. 2020 March. doi: 10.1542/peds.2020-0702). There were no deaths reported among these infants. Other case reports have documented COVID-19 in children aged as young as 2 days.

The document, which was assembled by members of the AAP Committee on Fetus and Newborn, Section on Neonatal Perinatal Medicine, and Committee on Infectious Diseases, pointed out that “considerable uncertainty” exists about the possibility for vertical transmission of SARS-CoV-2 from infected pregnant women to their newborns. “Evidence-based guidelines for managing antenatal, intrapartum, and neonatal care around COVID-19 would require an understanding of whether the virus can be transmitted transplacentally; a determination of which maternal body fluids may be infectious; and data of adequate statistical power that describe which maternal, intrapartum, and neonatal factors influence perinatal transmission,” according to the document. “In the midst of the pandemic these data do not exist, with only limited information currently available to address these issues.”

Based on the best available evidence, the guidance authors recommend that clinicians temporarily separate newborns from affected mothers to minimize the risk of postnatal infant infection from maternal respiratory secretions. “Newborns should be bathed as soon as reasonably possible after birth to remove virus potentially present on skin surfaces,” they wrote. “Clinical staff should use airborne, droplet, and contact precautions until newborn virologic status is known to be negative by SARS-CoV-2 [polymerase chain reaction] testing.”

While SARS-CoV-2 has not been detected in breast milk to date, the authors noted that mothers with COVID-19 can express breast milk to be fed to their infants by uninfected caregivers until specific maternal criteria are met. In addition, infants born to mothers with COVID-19 should be tested for SARS-CoV-2 at 24 hours and, if still in the birth facility, at 48 hours after birth. Centers with limited resources for testing may make individual risk/benefit decisions regarding testing.

For infants infected with SARS-CoV-2 but have no symptoms of the disease, they “may be discharged home on a case-by-case basis with appropriate precautions and plans for frequent outpatient follow-up contacts (either by phone, telemedicine, or in office) through 14 days after birth,” according to the document.

If both infant and mother are discharged from the hospital and the mother still has COVID-19 symptoms, she should maintain at least 6 feet of distance from the baby; if she is in closer proximity she should use a mask and hand hygiene. The mother can stop such precautions until she is afebrile without the use of antipyretics for at least 72 hours, and it is at least 7 days since her symptoms first occurred.

In cases where infants require ongoing neonatal intensive care, mothers infected with COVID-19 should not visit their newborn until she is afebrile without the use of antipyretics for at least 72 hours, her respiratory symptoms are improved, and she has negative results of a molecular assay for detection of SARS-CoV-2 from at least two consecutive nasopharyngeal swab specimens collected at least 24 hours apart.

[email protected]
 

As clinicians grapple with the COVID-19 pandemic, the American Academy of Pediatrics has released interim guidance on managing infants born of infected mothers.

CDC/ Dr. Fred Murphy; Sylvia Whitfield

“Pediatric cases of COVID-19 are so far reported as less severe than disease occurring among older individuals,” Karen M. Puopolo, MD, PhD, a neonatologist and chief of the section on newborn pediatrics at Pennsylvania Hospital, Philadelphia, and coauthors wrote in the 18-page document, which was released on April 2, 2020, along with an abbreviated “Frequently Asked Questions” summary. However, one study of children with COVID-19 in China found that 12% of confirmed cases occurred among 731 infants aged less than 1 year; 24% of those 86 infants “suffered severe or critical illness” (Pediatrics. 2020 March. doi: 10.1542/peds.2020-0702). There were no deaths reported among these infants. Other case reports have documented COVID-19 in children aged as young as 2 days.

The document, which was assembled by members of the AAP Committee on Fetus and Newborn, Section on Neonatal Perinatal Medicine, and Committee on Infectious Diseases, pointed out that “considerable uncertainty” exists about the possibility for vertical transmission of SARS-CoV-2 from infected pregnant women to their newborns. “Evidence-based guidelines for managing antenatal, intrapartum, and neonatal care around COVID-19 would require an understanding of whether the virus can be transmitted transplacentally; a determination of which maternal body fluids may be infectious; and data of adequate statistical power that describe which maternal, intrapartum, and neonatal factors influence perinatal transmission,” according to the document. “In the midst of the pandemic these data do not exist, with only limited information currently available to address these issues.”

Based on the best available evidence, the guidance authors recommend that clinicians temporarily separate newborns from affected mothers to minimize the risk of postnatal infant infection from maternal respiratory secretions. “Newborns should be bathed as soon as reasonably possible after birth to remove virus potentially present on skin surfaces,” they wrote. “Clinical staff should use airborne, droplet, and contact precautions until newborn virologic status is known to be negative by SARS-CoV-2 [polymerase chain reaction] testing.”

While SARS-CoV-2 has not been detected in breast milk to date, the authors noted that mothers with COVID-19 can express breast milk to be fed to their infants by uninfected caregivers until specific maternal criteria are met. In addition, infants born to mothers with COVID-19 should be tested for SARS-CoV-2 at 24 hours and, if still in the birth facility, at 48 hours after birth. Centers with limited resources for testing may make individual risk/benefit decisions regarding testing.

For infants infected with SARS-CoV-2 but have no symptoms of the disease, they “may be discharged home on a case-by-case basis with appropriate precautions and plans for frequent outpatient follow-up contacts (either by phone, telemedicine, or in office) through 14 days after birth,” according to the document.

If both infant and mother are discharged from the hospital and the mother still has COVID-19 symptoms, she should maintain at least 6 feet of distance from the baby; if she is in closer proximity she should use a mask and hand hygiene. The mother can stop such precautions until she is afebrile without the use of antipyretics for at least 72 hours, and it is at least 7 days since her symptoms first occurred.

In cases where infants require ongoing neonatal intensive care, mothers infected with COVID-19 should not visit their newborn until she is afebrile without the use of antipyretics for at least 72 hours, her respiratory symptoms are improved, and she has negative results of a molecular assay for detection of SARS-CoV-2 from at least two consecutive nasopharyngeal swab specimens collected at least 24 hours apart.

[email protected]
 

Influenza activity measures dropped during the week ending March 28, but the percentage of deaths attributed to pneumonia and influenza (P&I) has risen into epidemic territory, according to the Centers for Disease Control and Prevention.

This influenza news, however, needs to be viewed through a COVID-19 lens.

The P&I mortality data are reported together and are always a week behind the other measures, in this case covering the week ending March 21, but they show influenza deaths dropping to 0.8% as the overall P&I rate rose from 7.4% to 8.2%, a pneumonia-fueled increase that was “likely associated with COVID-19 rather than influenza,” the CDC’s influenza division noted.

The two main activity measures, at least, are on the same page for the first time since the end of February.

The rate of outpatient visits for influenza-like illness (ILI) had been dropping up to that point but then rose for an unprecedented third time this season, a change probably brought about by COVID-related health care–seeking behavior, the influenza division reported in its weekly FluView report.

This corresponding third drop in ILI activity brought the rate down to 5.4% this week from 6.2% the previous week, the CDC reported. The two previous high points occurred during the weeks ending Dec. 28 (7.0%) and Feb. 8 (6.7%)

The COVID-related changes, such as increased use of telemedicine and social distancing, “impact data from [the Outpatient Influenza-Like Illness Surveillance Network] in ways that are difficult to differentiate from changes in illness levels and should be interpreted with caution,” the CDC investigators noted.

The other activity measure, positive tests of respiratory specimens for influenza at clinical laboratories, continued the decline that started in mid-February by falling from 7.3% to 2.1%, its lowest rate since October, CDC data show.

Overall flu-related deaths may be down, but mortality in children continued at a near-record level. Seven such deaths were reported this past week, which brings the total for the 2019-2020 season to 162. “This number is higher than recorded at the same time in every season since reporting began in 2004-05, except for the 2009 pandemic,” the CDC noted.

[email protected]

Influenza activity measures dropped during the week ending March 28, but the percentage of deaths attributed to pneumonia and influenza (P&I) has risen into epidemic territory, according to the Centers for Disease Control and Prevention.

This influenza news, however, needs to be viewed through a COVID-19 lens.

The P&I mortality data are reported together and are always a week behind the other measures, in this case covering the week ending March 21, but they show influenza deaths dropping to 0.8% as the overall P&I rate rose from 7.4% to 8.2%, a pneumonia-fueled increase that was “likely associated with COVID-19 rather than influenza,” the CDC’s influenza division noted.

The two main activity measures, at least, are on the same page for the first time since the end of February.

The rate of outpatient visits for influenza-like illness (ILI) had been dropping up to that point but then rose for an unprecedented third time this season, a change probably brought about by COVID-related health care–seeking behavior, the influenza division reported in its weekly FluView report.

This corresponding third drop in ILI activity brought the rate down to 5.4% this week from 6.2% the previous week, the CDC reported. The two previous high points occurred during the weeks ending Dec. 28 (7.0%) and Feb. 8 (6.7%)

The COVID-related changes, such as increased use of telemedicine and social distancing, “impact data from [the Outpatient Influenza-Like Illness Surveillance Network] in ways that are difficult to differentiate from changes in illness levels and should be interpreted with caution,” the CDC investigators noted.

The other activity measure, positive tests of respiratory specimens for influenza at clinical laboratories, continued the decline that started in mid-February by falling from 7.3% to 2.1%, its lowest rate since October, CDC data show.

Overall flu-related deaths may be down, but mortality in children continued at a near-record level. Seven such deaths were reported this past week, which brings the total for the 2019-2020 season to 162. “This number is higher than recorded at the same time in every season since reporting began in 2004-05, except for the 2009 pandemic,” the CDC noted.

[email protected]

Influenza activity measures dropped during the week ending March 28, but the percentage of deaths attributed to pneumonia and influenza (P&I) has risen into epidemic territory, according to the Centers for Disease Control and Prevention.

This influenza news, however, needs to be viewed through a COVID-19 lens.

The P&I mortality data are reported together and are always a week behind the other measures, in this case covering the week ending March 21, but they show influenza deaths dropping to 0.8% as the overall P&I rate rose from 7.4% to 8.2%, a pneumonia-fueled increase that was “likely associated with COVID-19 rather than influenza,” the CDC’s influenza division noted.

The two main activity measures, at least, are on the same page for the first time since the end of February.

The rate of outpatient visits for influenza-like illness (ILI) had been dropping up to that point but then rose for an unprecedented third time this season, a change probably brought about by COVID-related health care–seeking behavior, the influenza division reported in its weekly FluView report.

This corresponding third drop in ILI activity brought the rate down to 5.4% this week from 6.2% the previous week, the CDC reported. The two previous high points occurred during the weeks ending Dec. 28 (7.0%) and Feb. 8 (6.7%)

The COVID-related changes, such as increased use of telemedicine and social distancing, “impact data from [the Outpatient Influenza-Like Illness Surveillance Network] in ways that are difficult to differentiate from changes in illness levels and should be interpreted with caution,” the CDC investigators noted.

The other activity measure, positive tests of respiratory specimens for influenza at clinical laboratories, continued the decline that started in mid-February by falling from 7.3% to 2.1%, its lowest rate since October, CDC data show.

Overall flu-related deaths may be down, but mortality in children continued at a near-record level. Seven such deaths were reported this past week, which brings the total for the 2019-2020 season to 162. “This number is higher than recorded at the same time in every season since reporting began in 2004-05, except for the 2009 pandemic,” the CDC noted.

[email protected]

Levels of three vascular biomarkers – hepatocyte growth factor, soluble Flt-1, and platelet-derived growth factor – were elevated a mean of 3 years before systemic sclerosis (SSc) patients developed pulmonary hypertension (PH) in a prospective cohort of 300 subjects.

However, the associations with PH were not very robust. For instance, above an optimal cut point of 9.89 pg/mL for platelet-derived growth factor (PlGF), the sensitivity for future PH was 82%, specificity 56%, and area under the curve (AUC) 0.69. An elevation above the optimal cut point for soluble Flt-1 (sFlt1) – 93.8 pg/mL – was 71% specific and 51% sensitive, with an AUC of 0.61.

Adding PlGF and sFlt1 elevations to carbon monoxide diffusing capacity, N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) level, and percent forced vital capacity to predict PH increased the AUC modestly, from 0.72 to 0.77.

The data suggest, perhaps, an early warning system for PH. “Once vascular biomarkers are observed to be elevated, the frequency of other screening tests (e.g., NT-proBNP, DLCO) may be increased in a more cost-effective approach,” wrote investigators led by rheumatologist Christopher Mecoli, MD, an assistant professor at Johns Hopkins University, Baltimore, in Arthritis & Rheumatology.

“In the end, the authors did not overstate the case and cautiously recommended that using biomarkers might be useful in the future. The finding that when there are increased numbers of abnormalities of vascular markers, there would be an increased probability of pulmonary hypertension, makes sense.” However, “this was a major fishing expedition, and the data are certainly not sufficient to suggest anything clinical but are of some interest with respect to the general hypothesis,” said rheumatologist Daniel Furst, MD, professor of medicine (emeritus) at the University of California, Los Angeles, when asked for comment.

The subjects were followed for at least 5 years and had no evidence of PH at study entry. Levels of P1GF, sFlt-1, hepatocyte growth factor (HGF), soluble endoglin, and endostatin were assessed at baseline and at regular intervals thereafter. A total of 46 patients (15%) developed PH after a mean of 3 years.

Risk of PH was associated with baseline elevations of HGF (hazard ratio, 1.99; 95% CI, 1.24-3.17; P = .004); sFlt1 (HR, 3.04; 95% CI, 1.29-7.14; P = .011); and PlGF (HR, 2.74; 95% CI, 1.32-5.69; P = .007).

Just 2 of 25 patients (8%) with no biomarkers elevated at baseline developed PH versus 12 of 29 (42%) with all five elevated. That translated to a dose-response relationship, with each additional elevated biomarker increasing the risk of PH by 78% (95% CI, 1.2-2.6; P = .004).

“There [was] no consistent trend of increasing biomarker levels over time as patients approach[ed] a diagnosis of [PH]. ... Serial testing may have value in patients with early disease to first detect elevations in biomarkers,” but “once elevated, the utility of serially monitoring appears low,” the investigators wrote.

It’s not surprising that “a higher number of elevated biomarkers relating to vascular dysfunction would correspond to a higher risk of PH,” the team wrote. However, “while these biomarkers hold promise in the risk stratification of SSc patients, many more vascular molecules exist which may have similar or greater value.”

There was no substantial correlation between any biomarker and disease duration, age at enrollment, or age at diagnosis, and no significant difference in biomarker level based on patient comorbidities. No biomarker was significantly associated with medication use at cohort entry, and none were significantly associated with the risk of ischemic digital lesions.

The majority of patients were white women. At enrollment, the average age was 52 years, and subjects had SSc for a mean of 10 years.

The work was funded by the National Institutes of Health, among others. Investigator disclosures were not reported.

[email protected]

SOURCE: Mecoli C et al. Arthritis Rheumatol. 2020 Mar 21. doi: 10.1002/art.41265.

Levels of three vascular biomarkers – hepatocyte growth factor, soluble Flt-1, and platelet-derived growth factor – were elevated a mean of 3 years before systemic sclerosis (SSc) patients developed pulmonary hypertension (PH) in a prospective cohort of 300 subjects.

However, the associations with PH were not very robust. For instance, above an optimal cut point of 9.89 pg/mL for platelet-derived growth factor (PlGF), the sensitivity for future PH was 82%, specificity 56%, and area under the curve (AUC) 0.69. An elevation above the optimal cut point for soluble Flt-1 (sFlt1) – 93.8 pg/mL – was 71% specific and 51% sensitive, with an AUC of 0.61.

Adding PlGF and sFlt1 elevations to carbon monoxide diffusing capacity, N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) level, and percent forced vital capacity to predict PH increased the AUC modestly, from 0.72 to 0.77.

The data suggest, perhaps, an early warning system for PH. “Once vascular biomarkers are observed to be elevated, the frequency of other screening tests (e.g., NT-proBNP, DLCO) may be increased in a more cost-effective approach,” wrote investigators led by rheumatologist Christopher Mecoli, MD, an assistant professor at Johns Hopkins University, Baltimore, in Arthritis & Rheumatology.

“In the end, the authors did not overstate the case and cautiously recommended that using biomarkers might be useful in the future. The finding that when there are increased numbers of abnormalities of vascular markers, there would be an increased probability of pulmonary hypertension, makes sense.” However, “this was a major fishing expedition, and the data are certainly not sufficient to suggest anything clinical but are of some interest with respect to the general hypothesis,” said rheumatologist Daniel Furst, MD, professor of medicine (emeritus) at the University of California, Los Angeles, when asked for comment.

The subjects were followed for at least 5 years and had no evidence of PH at study entry. Levels of P1GF, sFlt-1, hepatocyte growth factor (HGF), soluble endoglin, and endostatin were assessed at baseline and at regular intervals thereafter. A total of 46 patients (15%) developed PH after a mean of 3 years.

Risk of PH was associated with baseline elevations of HGF (hazard ratio, 1.99; 95% CI, 1.24-3.17; P = .004); sFlt1 (HR, 3.04; 95% CI, 1.29-7.14; P = .011); and PlGF (HR, 2.74; 95% CI, 1.32-5.69; P = .007).

Just 2 of 25 patients (8%) with no biomarkers elevated at baseline developed PH versus 12 of 29 (42%) with all five elevated. That translated to a dose-response relationship, with each additional elevated biomarker increasing the risk of PH by 78% (95% CI, 1.2-2.6; P = .004).

“There [was] no consistent trend of increasing biomarker levels over time as patients approach[ed] a diagnosis of [PH]. ... Serial testing may have value in patients with early disease to first detect elevations in biomarkers,” but “once elevated, the utility of serially monitoring appears low,” the investigators wrote.

It’s not surprising that “a higher number of elevated biomarkers relating to vascular dysfunction would correspond to a higher risk of PH,” the team wrote. However, “while these biomarkers hold promise in the risk stratification of SSc patients, many more vascular molecules exist which may have similar or greater value.”

There was no substantial correlation between any biomarker and disease duration, age at enrollment, or age at diagnosis, and no significant difference in biomarker level based on patient comorbidities. No biomarker was significantly associated with medication use at cohort entry, and none were significantly associated with the risk of ischemic digital lesions.

The majority of patients were white women. At enrollment, the average age was 52 years, and subjects had SSc for a mean of 10 years.

The work was funded by the National Institutes of Health, among others. Investigator disclosures were not reported.

[email protected]

SOURCE: Mecoli C et al. Arthritis Rheumatol. 2020 Mar 21. doi: 10.1002/art.41265.

Levels of three vascular biomarkers – hepatocyte growth factor, soluble Flt-1, and platelet-derived growth factor – were elevated a mean of 3 years before systemic sclerosis (SSc) patients developed pulmonary hypertension (PH) in a prospective cohort of 300 subjects.

However, the associations with PH were not very robust. For instance, above an optimal cut point of 9.89 pg/mL for platelet-derived growth factor (PlGF), the sensitivity for future PH was 82%, specificity 56%, and area under the curve (AUC) 0.69. An elevation above the optimal cut point for soluble Flt-1 (sFlt1) – 93.8 pg/mL – was 71% specific and 51% sensitive, with an AUC of 0.61.

Adding PlGF and sFlt1 elevations to carbon monoxide diffusing capacity, N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) level, and percent forced vital capacity to predict PH increased the AUC modestly, from 0.72 to 0.77.

The data suggest, perhaps, an early warning system for PH. “Once vascular biomarkers are observed to be elevated, the frequency of other screening tests (e.g., NT-proBNP, DLCO) may be increased in a more cost-effective approach,” wrote investigators led by rheumatologist Christopher Mecoli, MD, an assistant professor at Johns Hopkins University, Baltimore, in Arthritis & Rheumatology.

“In the end, the authors did not overstate the case and cautiously recommended that using biomarkers might be useful in the future. The finding that when there are increased numbers of abnormalities of vascular markers, there would be an increased probability of pulmonary hypertension, makes sense.” However, “this was a major fishing expedition, and the data are certainly not sufficient to suggest anything clinical but are of some interest with respect to the general hypothesis,” said rheumatologist Daniel Furst, MD, professor of medicine (emeritus) at the University of California, Los Angeles, when asked for comment.

The subjects were followed for at least 5 years and had no evidence of PH at study entry. Levels of P1GF, sFlt-1, hepatocyte growth factor (HGF), soluble endoglin, and endostatin were assessed at baseline and at regular intervals thereafter. A total of 46 patients (15%) developed PH after a mean of 3 years.

Risk of PH was associated with baseline elevations of HGF (hazard ratio, 1.99; 95% CI, 1.24-3.17; P = .004); sFlt1 (HR, 3.04; 95% CI, 1.29-7.14; P = .011); and PlGF (HR, 2.74; 95% CI, 1.32-5.69; P = .007).

Just 2 of 25 patients (8%) with no biomarkers elevated at baseline developed PH versus 12 of 29 (42%) with all five elevated. That translated to a dose-response relationship, with each additional elevated biomarker increasing the risk of PH by 78% (95% CI, 1.2-2.6; P = .004).

“There [was] no consistent trend of increasing biomarker levels over time as patients approach[ed] a diagnosis of [PH]. ... Serial testing may have value in patients with early disease to first detect elevations in biomarkers,” but “once elevated, the utility of serially monitoring appears low,” the investigators wrote.

It’s not surprising that “a higher number of elevated biomarkers relating to vascular dysfunction would correspond to a higher risk of PH,” the team wrote. However, “while these biomarkers hold promise in the risk stratification of SSc patients, many more vascular molecules exist which may have similar or greater value.”

There was no substantial correlation between any biomarker and disease duration, age at enrollment, or age at diagnosis, and no significant difference in biomarker level based on patient comorbidities. No biomarker was significantly associated with medication use at cohort entry, and none were significantly associated with the risk of ischemic digital lesions.

The majority of patients were white women. At enrollment, the average age was 52 years, and subjects had SSc for a mean of 10 years.

The work was funded by the National Institutes of Health, among others. Investigator disclosures were not reported.

[email protected]

SOURCE: Mecoli C et al. Arthritis Rheumatol. 2020 Mar 21. doi: 10.1002/art.41265.

Almost all patients who develop gastrointestinal side effects from oral immunotherapy for severe food allergies develop some degree of esophageal eosinophilia, but that eventually resolves in most of them after a year of treatment, according to results of a pilot study that was to be presented at the American Academy of Allergy, Asthma & Immunology annual meeting. The AAAAI canceled the meeting and provided abstracts and access to presenters for press coverage.

The findings may help identify biomarkers of persistent eosinophilia despite oral immunotherapy.

In January of this year the Food and Drug Administration approved oral immunotherapy (OIT), known as peanut allergen powder-dnfp, or peanut OIT (POIT), for severe food allergies. In an interview, lead study author Benjamin Wright, MD, of the Mayo Clinic, Phoenix, said OIT is a “promising proactive” treatment for food allergies. “But questions regarding the safety of immunotherapy remain,” he said. “About 30% of patients can develop GI side effects, including abdominal pain and vomiting; most concerning is that some patients develop eosinophilic esophagitis (EoE).”

The pilot study was a mechanistic substudy of 20 adult patients with immunoglobulin E–mediated peanut allergies enrolled in the phase 2 Peanut Oral Immunotherapy Safety, Efficacy and Discovery trial (POISED), with 15 randomized to treatment and the remainder to placebo. They had serial gastrointestinal biopsies at baseline (n = 20), 1 year (n = 7 treatment, 3 placebo) and 2 years (n = 7 treatment, 4 placebo) to evaluate eosinophils per high-power field (eos/hpf).

Baseline characteristics between the treatment and placebo groups were similar, with some having signs of preexisting disease. About 14% of them had clinically significant EoE, represented as a measure of more than 15 eos/hpf, Dr. Wright said. “One of the findings that was really fascinating to us was that all of the subjects had evidence of dilated intercellular spaces at baseline,” he said. “This indicates that all the subjects have some degree of epithelial barrier dysfunction before they start OIT.” Dilated intercellular spaces are a marker of inflammation.

Four patients in the treatment group had mild endoscopic findings at weeks 52 and 104, as did one patient on placebo, Dr. Wright said. A plot of eosinophil counts showed a peak at 52 weeks but near resolution at 104 weeks for all but one patient on OIT. “One of the most interesting trends that we noted was that, for most of patients, OIT-induced eosinophilia was transient and not fixed,” he said. “We noted a triangle pattern where tissue eosinophilia peaks and then resolves with the continuation of therapy.” EoE Histologic scoring system results followed a similar pattern in these patients, he added.

Also, results of the comprehensive GI Symptom Questionnaire, which assessed symptoms such as abdominal pain, difficulty swallowing, refusal to eat, and vomiting, showed that patient-reported GI symptoms did not correlate with tissue eosinophilia, Dr. Wright said. “To us, that suggests that perhaps eosinophils are not central to disease pathology or symptom development in these patients,” he said.

However, the findings validate that, in a small number of patients, OIT induces EoE, Dr. Wright said. He used a treadmill analogy to explain how OIT influences epithelial remodeling in some patients. “We’re constantly renewing our esophageal epithelium every 2 weeks, and when you challenge it with an antigen (i.e., OIT), the treadmill speeds up,” he said. “There may be some patients who will fall if the treadmill gets too fast, and they develop disease.”

He added, “Distinguishing someone’s fitness before they get on the treadmill is really going be a key moving forward in determining which subjects are good participants for OIT or how to dose OIT.”

Dr. Wright reported receiving grants from the Arizona Biomedical Research Consortium and Phoenix Children’s Hospital Foundation. Coauthors reported receiving grants from the National Institutes of Health and the Consortium for Food Allergy Research, as well as relationships with Aimmune Therapeutics, Regeneron Pharmaceuticals, Sanofi, Consortium for Food Allergy Research, DBV Technologies, Astellas, AnaptysBio, and Novartis.

SOURCE: Wright B et al. AAAAI, Session 2605, Abstract No. 259.

Almost all patients who develop gastrointestinal side effects from oral immunotherapy for severe food allergies develop some degree of esophageal eosinophilia, but that eventually resolves in most of them after a year of treatment, according to results of a pilot study that was to be presented at the American Academy of Allergy, Asthma & Immunology annual meeting. The AAAAI canceled the meeting and provided abstracts and access to presenters for press coverage.

The findings may help identify biomarkers of persistent eosinophilia despite oral immunotherapy.

In January of this year the Food and Drug Administration approved oral immunotherapy (OIT), known as peanut allergen powder-dnfp, or peanut OIT (POIT), for severe food allergies. In an interview, lead study author Benjamin Wright, MD, of the Mayo Clinic, Phoenix, said OIT is a “promising proactive” treatment for food allergies. “But questions regarding the safety of immunotherapy remain,” he said. “About 30% of patients can develop GI side effects, including abdominal pain and vomiting; most concerning is that some patients develop eosinophilic esophagitis (EoE).”

The pilot study was a mechanistic substudy of 20 adult patients with immunoglobulin E–mediated peanut allergies enrolled in the phase 2 Peanut Oral Immunotherapy Safety, Efficacy and Discovery trial (POISED), with 15 randomized to treatment and the remainder to placebo. They had serial gastrointestinal biopsies at baseline (n = 20), 1 year (n = 7 treatment, 3 placebo) and 2 years (n = 7 treatment, 4 placebo) to evaluate eosinophils per high-power field (eos/hpf).

Baseline characteristics between the treatment and placebo groups were similar, with some having signs of preexisting disease. About 14% of them had clinically significant EoE, represented as a measure of more than 15 eos/hpf, Dr. Wright said. “One of the findings that was really fascinating to us was that all of the subjects had evidence of dilated intercellular spaces at baseline,” he said. “This indicates that all the subjects have some degree of epithelial barrier dysfunction before they start OIT.” Dilated intercellular spaces are a marker of inflammation.

Four patients in the treatment group had mild endoscopic findings at weeks 52 and 104, as did one patient on placebo, Dr. Wright said. A plot of eosinophil counts showed a peak at 52 weeks but near resolution at 104 weeks for all but one patient on OIT. “One of the most interesting trends that we noted was that, for most of patients, OIT-induced eosinophilia was transient and not fixed,” he said. “We noted a triangle pattern where tissue eosinophilia peaks and then resolves with the continuation of therapy.” EoE Histologic scoring system results followed a similar pattern in these patients, he added.

Also, results of the comprehensive GI Symptom Questionnaire, which assessed symptoms such as abdominal pain, difficulty swallowing, refusal to eat, and vomiting, showed that patient-reported GI symptoms did not correlate with tissue eosinophilia, Dr. Wright said. “To us, that suggests that perhaps eosinophils are not central to disease pathology or symptom development in these patients,” he said.

However, the findings validate that, in a small number of patients, OIT induces EoE, Dr. Wright said. He used a treadmill analogy to explain how OIT influences epithelial remodeling in some patients. “We’re constantly renewing our esophageal epithelium every 2 weeks, and when you challenge it with an antigen (i.e., OIT), the treadmill speeds up,” he said. “There may be some patients who will fall if the treadmill gets too fast, and they develop disease.”

He added, “Distinguishing someone’s fitness before they get on the treadmill is really going be a key moving forward in determining which subjects are good participants for OIT or how to dose OIT.”

Dr. Wright reported receiving grants from the Arizona Biomedical Research Consortium and Phoenix Children’s Hospital Foundation. Coauthors reported receiving grants from the National Institutes of Health and the Consortium for Food Allergy Research, as well as relationships with Aimmune Therapeutics, Regeneron Pharmaceuticals, Sanofi, Consortium for Food Allergy Research, DBV Technologies, Astellas, AnaptysBio, and Novartis.

SOURCE: Wright B et al. AAAAI, Session 2605, Abstract No. 259.

Almost all patients who develop gastrointestinal side effects from oral immunotherapy for severe food allergies develop some degree of esophageal eosinophilia, but that eventually resolves in most of them after a year of treatment, according to results of a pilot study that was to be presented at the American Academy of Allergy, Asthma & Immunology annual meeting. The AAAAI canceled the meeting and provided abstracts and access to presenters for press coverage.

The findings may help identify biomarkers of persistent eosinophilia despite oral immunotherapy.

In January of this year the Food and Drug Administration approved oral immunotherapy (OIT), known as peanut allergen powder-dnfp, or peanut OIT (POIT), for severe food allergies. In an interview, lead study author Benjamin Wright, MD, of the Mayo Clinic, Phoenix, said OIT is a “promising proactive” treatment for food allergies. “But questions regarding the safety of immunotherapy remain,” he said. “About 30% of patients can develop GI side effects, including abdominal pain and vomiting; most concerning is that some patients develop eosinophilic esophagitis (EoE).”

The pilot study was a mechanistic substudy of 20 adult patients with immunoglobulin E–mediated peanut allergies enrolled in the phase 2 Peanut Oral Immunotherapy Safety, Efficacy and Discovery trial (POISED), with 15 randomized to treatment and the remainder to placebo. They had serial gastrointestinal biopsies at baseline (n = 20), 1 year (n = 7 treatment, 3 placebo) and 2 years (n = 7 treatment, 4 placebo) to evaluate eosinophils per high-power field (eos/hpf).

Baseline characteristics between the treatment and placebo groups were similar, with some having signs of preexisting disease. About 14% of them had clinically significant EoE, represented as a measure of more than 15 eos/hpf, Dr. Wright said. “One of the findings that was really fascinating to us was that all of the subjects had evidence of dilated intercellular spaces at baseline,” he said. “This indicates that all the subjects have some degree of epithelial barrier dysfunction before they start OIT.” Dilated intercellular spaces are a marker of inflammation.

Four patients in the treatment group had mild endoscopic findings at weeks 52 and 104, as did one patient on placebo, Dr. Wright said. A plot of eosinophil counts showed a peak at 52 weeks but near resolution at 104 weeks for all but one patient on OIT. “One of the most interesting trends that we noted was that, for most of patients, OIT-induced eosinophilia was transient and not fixed,” he said. “We noted a triangle pattern where tissue eosinophilia peaks and then resolves with the continuation of therapy.” EoE Histologic scoring system results followed a similar pattern in these patients, he added.

Also, results of the comprehensive GI Symptom Questionnaire, which assessed symptoms such as abdominal pain, difficulty swallowing, refusal to eat, and vomiting, showed that patient-reported GI symptoms did not correlate with tissue eosinophilia, Dr. Wright said. “To us, that suggests that perhaps eosinophils are not central to disease pathology or symptom development in these patients,” he said.

However, the findings validate that, in a small number of patients, OIT induces EoE, Dr. Wright said. He used a treadmill analogy to explain how OIT influences epithelial remodeling in some patients. “We’re constantly renewing our esophageal epithelium every 2 weeks, and when you challenge it with an antigen (i.e., OIT), the treadmill speeds up,” he said. “There may be some patients who will fall if the treadmill gets too fast, and they develop disease.”

He added, “Distinguishing someone’s fitness before they get on the treadmill is really going be a key moving forward in determining which subjects are good participants for OIT or how to dose OIT.”

Dr. Wright reported receiving grants from the Arizona Biomedical Research Consortium and Phoenix Children’s Hospital Foundation. Coauthors reported receiving grants from the National Institutes of Health and the Consortium for Food Allergy Research, as well as relationships with Aimmune Therapeutics, Regeneron Pharmaceuticals, Sanofi, Consortium for Food Allergy Research, DBV Technologies, Astellas, AnaptysBio, and Novartis.

SOURCE: Wright B et al. AAAAI, Session 2605, Abstract No. 259.

Clinical question: Are blood cultures warranted in specific subsets of children hospitalized with community-acquired pneumonia (CAP)?

Background: Guidelines from the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America recommend obtaining blood cultures in children hospitalized with moderate to severe community-acquired pneumonia. This group of authors recently published a study showing the prevalence of bacteremia of 2.5% in a cohort of generally healthy children hospitalized with CAP who had blood cultures obtained, with only 0.4% harboring a pathogen not susceptible to penicillin. They found low yield for blood cultures in children hospitalized with CAP.

Study design: Retrospective Cohort Study.

Setting: Pediatric Health Information System Plus (PHIS+) database (six institutions).

Synopsis: Secondary analysis of prior study of children aged 3 months to 18 years hospitalized with CAP between 2007 to 2011. For the secondary analysis only children in whom a blood culture was obtained on the initial or second day of hospitalization were studied. CAP was defined by a primary ICD-9 discharge diagnosis code for pneumonia or a primary ICD-9 discharge diagnosis code for pleural effusion with a secondary diagnosis code for pneumonia. Children transferred into the study institution and children with complex chronic conditions were excluded from the study. The primary outcome was the presence of bacteremia based on pathogen detection in the initial blood culture. Bacteria were labeled as pathogens or contaminants.

A total of 7,509 children were included in the initial study. Of them, 2,568 (34.2%) had a blood culture obtained on the initial or second day of hospitalization; 65 (2.5%) of the children with blood cultures obtained on admission had bacteremia. The most common penicillin-susceptible blood pathogen isolated was Streptococcus pneumoniae (n = 47). Eleven children (0.4%) had bacteremia with a pathogen not susceptible to penicillin. Children with bacteremia had a higher median admission white blood cell (WBC) count than did those without bacteremia (17.5 × 10³ cells per mcL vs. 12.4 × 10³ cells per mcL; P < .01) and definite radiographic pneumonia on admission chest radiograph (P < .01). C-reactive protein and erythrocyte sedimentation rate were also higher in children with bacteremia but were only obtained in 35% and 15% of patients, respectively. Children with bacteremia had a higher prevalence of complicated pneumonia on admission (P = .06) than did children without bacteremia. Children with bacteremia had longer lengths of stay (4 days vs. 2 days; P < .01) and were more likely to be admitted to an ICU (P < .01) than were children without bacteremia.

This study is limited by its sample because all of the patients were cared for at tertiary care hospitals. It is also limited by its timing; the PHIS+ data set spans the introduction of the 13-valent pneumococcal vaccine, and so the current prevalence of bacteremia in CAP may be lower than that found in the study.

Bottom line: The prevalence of bacteremia was low among a cohort of generally healthy children hospitalized with CAP, and no features strongly predicted the presence of bacteremia. The authors recommend that blood cultures in children with CAP should be limited to patients admitted to the ICU.

Citation: Lipsett SC et al. Predictors of Bacteremia in Children Hospitalized With Community-Acquired Pneumonia. Hosp Pediatr. 2019 Oct;9(10):770-8.

Dr. Kumar is a pediatric hospitalist at Cleveland Clinic Children’s. She is a clinical assistant professor of pediatrics at Case Western Reserve University, Cleveland, and serves as the Pediatrics Editor for The Hospitalist.

Clinical question: Are blood cultures warranted in specific subsets of children hospitalized with community-acquired pneumonia (CAP)?

Background: Guidelines from the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America recommend obtaining blood cultures in children hospitalized with moderate to severe community-acquired pneumonia. This group of authors recently published a study showing the prevalence of bacteremia of 2.5% in a cohort of generally healthy children hospitalized with CAP who had blood cultures obtained, with only 0.4% harboring a pathogen not susceptible to penicillin. They found low yield for blood cultures in children hospitalized with CAP.

Study design: Retrospective Cohort Study.

Setting: Pediatric Health Information System Plus (PHIS+) database (six institutions).

Synopsis: Secondary analysis of prior study of children aged 3 months to 18 years hospitalized with CAP between 2007 to 2011. For the secondary analysis only children in whom a blood culture was obtained on the initial or second day of hospitalization were studied. CAP was defined by a primary ICD-9 discharge diagnosis code for pneumonia or a primary ICD-9 discharge diagnosis code for pleural effusion with a secondary diagnosis code for pneumonia. Children transferred into the study institution and children with complex chronic conditions were excluded from the study. The primary outcome was the presence of bacteremia based on pathogen detection in the initial blood culture. Bacteria were labeled as pathogens or contaminants.

A total of 7,509 children were included in the initial study. Of them, 2,568 (34.2%) had a blood culture obtained on the initial or second day of hospitalization; 65 (2.5%) of the children with blood cultures obtained on admission had bacteremia. The most common penicillin-susceptible blood pathogen isolated was Streptococcus pneumoniae (n = 47). Eleven children (0.4%) had bacteremia with a pathogen not susceptible to penicillin. Children with bacteremia had a higher median admission white blood cell (WBC) count than did those without bacteremia (17.5 × 10³ cells per mcL vs. 12.4 × 10³ cells per mcL; P < .01) and definite radiographic pneumonia on admission chest radiograph (P < .01). C-reactive protein and erythrocyte sedimentation rate were also higher in children with bacteremia but were only obtained in 35% and 15% of patients, respectively. Children with bacteremia had a higher prevalence of complicated pneumonia on admission (P = .06) than did children without bacteremia. Children with bacteremia had longer lengths of stay (4 days vs. 2 days; P < .01) and were more likely to be admitted to an ICU (P < .01) than were children without bacteremia.

This study is limited by its sample because all of the patients were cared for at tertiary care hospitals. It is also limited by its timing; the PHIS+ data set spans the introduction of the 13-valent pneumococcal vaccine, and so the current prevalence of bacteremia in CAP may be lower than that found in the study.

Bottom line: The prevalence of bacteremia was low among a cohort of generally healthy children hospitalized with CAP, and no features strongly predicted the presence of bacteremia. The authors recommend that blood cultures in children with CAP should be limited to patients admitted to the ICU.

Citation: Lipsett SC et al. Predictors of Bacteremia in Children Hospitalized With Community-Acquired Pneumonia. Hosp Pediatr. 2019 Oct;9(10):770-8.

Dr. Kumar is a pediatric hospitalist at Cleveland Clinic Children’s. She is a clinical assistant professor of pediatrics at Case Western Reserve University, Cleveland, and serves as the Pediatrics Editor for The Hospitalist.

Clinical question: Are blood cultures warranted in specific subsets of children hospitalized with community-acquired pneumonia (CAP)?

Background: Guidelines from the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America recommend obtaining blood cultures in children hospitalized with moderate to severe community-acquired pneumonia. This group of authors recently published a study showing the prevalence of bacteremia of 2.5% in a cohort of generally healthy children hospitalized with CAP who had blood cultures obtained, with only 0.4% harboring a pathogen not susceptible to penicillin. They found low yield for blood cultures in children hospitalized with CAP.

Study design: Retrospective Cohort Study.

Setting: Pediatric Health Information System Plus (PHIS+) database (six institutions).

Synopsis: Secondary analysis of prior study of children aged 3 months to 18 years hospitalized with CAP between 2007 to 2011. For the secondary analysis only children in whom a blood culture was obtained on the initial or second day of hospitalization were studied. CAP was defined by a primary ICD-9 discharge diagnosis code for pneumonia or a primary ICD-9 discharge diagnosis code for pleural effusion with a secondary diagnosis code for pneumonia. Children transferred into the study institution and children with complex chronic conditions were excluded from the study. The primary outcome was the presence of bacteremia based on pathogen detection in the initial blood culture. Bacteria were labeled as pathogens or contaminants.

A total of 7,509 children were included in the initial study. Of them, 2,568 (34.2%) had a blood culture obtained on the initial or second day of hospitalization; 65 (2.5%) of the children with blood cultures obtained on admission had bacteremia. The most common penicillin-susceptible blood pathogen isolated was Streptococcus pneumoniae (n = 47). Eleven children (0.4%) had bacteremia with a pathogen not susceptible to penicillin. Children with bacteremia had a higher median admission white blood cell (WBC) count than did those without bacteremia (17.5 × 10³ cells per mcL vs. 12.4 × 10³ cells per mcL; P < .01) and definite radiographic pneumonia on admission chest radiograph (P < .01). C-reactive protein and erythrocyte sedimentation rate were also higher in children with bacteremia but were only obtained in 35% and 15% of patients, respectively. Children with bacteremia had a higher prevalence of complicated pneumonia on admission (P = .06) than did children without bacteremia. Children with bacteremia had longer lengths of stay (4 days vs. 2 days; P < .01) and were more likely to be admitted to an ICU (P < .01) than were children without bacteremia.

This study is limited by its sample because all of the patients were cared for at tertiary care hospitals. It is also limited by its timing; the PHIS+ data set spans the introduction of the 13-valent pneumococcal vaccine, and so the current prevalence of bacteremia in CAP may be lower than that found in the study.

Bottom line: The prevalence of bacteremia was low among a cohort of generally healthy children hospitalized with CAP, and no features strongly predicted the presence of bacteremia. The authors recommend that blood cultures in children with CAP should be limited to patients admitted to the ICU.

Citation: Lipsett SC et al. Predictors of Bacteremia in Children Hospitalized With Community-Acquired Pneumonia. Hosp Pediatr. 2019 Oct;9(10):770-8.

Dr. Kumar is a pediatric hospitalist at Cleveland Clinic Children’s. She is a clinical assistant professor of pediatrics at Case Western Reserve University, Cleveland, and serves as the Pediatrics Editor for The Hospitalist.

A small-molecule kinase inhibitor that targets a gene mutation complicit in systemic mastocytosis has been found to reduce symptoms by about 30%, according to early results of a clinical trial scheduled to be presented at the American Academy of Allergy, Asthma, and Immunology annual meeting. The AAAAI canceled the meeting and provided abstracts and access to presenters for press coverage.

“This correlates with reduction from very severe to moderate or from moderate to mild category, and all the reductions in symptoms were statistically significant,” Cem Akin, MD, of the University of Michigan, Ann Arbor, said in an interview. He reported on part 1 of the phase 2 PIONEER trial of the kinase inhibitor avapritinib, described as a potent and highly selective inhibitor of the KIT D816V mutation that affects 90% of patients with systemic mastocytosis.

Currently, Dr. Akin noted, patients with indolent or smoldering systemic mastocytosis must rely on over-the-counter antihistamines used for seasonal allergies. “These patients use antihistamines in higher doses because mastocytosis patients have higher counts of mast cells that release histamines that cause a variety of symptoms,” he said. Symptoms, which can occur suddenly, include flushing and reactions that resemble allergic or anaphylactic reactions.

The purpose of the part 1 study was to evaluate three different dosing levels of avapritinib vs. placebo: 25, 50, and 100 mg. Ten patients were in each dosing group and nine were in the placebo group. The primary outcome was reduction in total symptom scores at 16 weeks as measured by the Indolent SM Symptom Assessment Form. “All three dose groups showed significant reductions in total symptom scores as well as specific symptoms that were most bothersome to the patient, whether skin symptoms or GI or neurocognitive symptoms,” Dr. Akin said. “All three doses were effective; the average reduction was about 30% compared to baseline.” Specifically, 25-mg dosing showed an average 30% reduction, 50-mg dosing showed an average 19% reduction, and 100-mg dosing showed an average 35% reduction.

The researchers determined that the 25-mg daily dose was the most effective and safest, with no patients on the dose reporting grade 3 adverse events, Dr. Akin said. In total 20% and 40% of the 50- and 100-mg dose groups, respectively, reported grade 3 AEs, according to study results.* The 25-mg daily dose will be evaluated in part 2 of the trial. The trial is estimated to enroll 112 total patients, according to the ClinicalTrials.gov filing. In part 3, patients who complete parts 1 or 2, including those initially randomized to placebo, may participate in a long-term open-label extension, receiving 25 mg avapritinib plus best supportive care.

“This is targeting a population whose symptoms are not controlled by antihistamines, based on a minimum total symptom score according to diaries they fill out, and they have to be on at least two different systemic medications – antihistamine or proton-pump inhibitor and leukotriene inhibitor – and they still have significant symptoms,” Dr. Akin said. He estimated that this describes about two-thirds of his patients with indolent or smoldering systematic mastocytosis.

“This is a disease that also takes a psychological toll,” he said. “This is a problem that starts in the bone marrow; it is similar to a hematological stem-cell disorder that affects the mast cell progenitor and it’s caused by a mutation that has not been particularly targeted until this drug,” he said. While most of these patients live with a benign mastocytosis their entire lives, the symptoms can be debilitating to the point where the disease disrupts and restricts social activities and comprises their quality of life, he said.

“This is a groundbreaking therapy that will change the way we think about mastocytosis treatment going forward,” Dr. Akin said. “It’s the first time we are actually targeting the underlying mutation that’s causing the disease, in terms of reducing directly that mutation as opposed to just treating the symptoms in indolent disease.”

Scheduled session moderator Anil Nanda, MD, of the Asthma and Allergy Center in Lewisville, Texas, said the findings are encouraging. “As a practicing allergist and immunologist in the community, it is very exciting to have a potential new treatment option for indolent or smoldering systemic mastocytosis,” he said via email. “Patients appreciate new options in therapy.”

Dr. Akin, the primary investigator, receives funding from and serves as a consultant for Blueprint Medicines, which sponsored the trial. He also disclosed a financial relationship with Novartis.

SOURCE: Akin C et al. AAAAI 2020, Presentation L5.

*Correction, 4/6/2020: An earlier version of this story misstated the percentage of grade 3 adverse events. In total 20% and 40% of the 50- and 100-mg dose groups, respectively, reported grade 3 adverse events.  

A small-molecule kinase inhibitor that targets a gene mutation complicit in systemic mastocytosis has been found to reduce symptoms by about 30%, according to early results of a clinical trial scheduled to be presented at the American Academy of Allergy, Asthma, and Immunology annual meeting. The AAAAI canceled the meeting and provided abstracts and access to presenters for press coverage.

“This correlates with reduction from very severe to moderate or from moderate to mild category, and all the reductions in symptoms were statistically significant,” Cem Akin, MD, of the University of Michigan, Ann Arbor, said in an interview. He reported on part 1 of the phase 2 PIONEER trial of the kinase inhibitor avapritinib, described as a potent and highly selective inhibitor of the KIT D816V mutation that affects 90% of patients with systemic mastocytosis.

Currently, Dr. Akin noted, patients with indolent or smoldering systemic mastocytosis must rely on over-the-counter antihistamines used for seasonal allergies. “These patients use antihistamines in higher doses because mastocytosis patients have higher counts of mast cells that release histamines that cause a variety of symptoms,” he said. Symptoms, which can occur suddenly, include flushing and reactions that resemble allergic or anaphylactic reactions.

The purpose of the part 1 study was to evaluate three different dosing levels of avapritinib vs. placebo: 25, 50, and 100 mg. Ten patients were in each dosing group and nine were in the placebo group. The primary outcome was reduction in total symptom scores at 16 weeks as measured by the Indolent SM Symptom Assessment Form. “All three dose groups showed significant reductions in total symptom scores as well as specific symptoms that were most bothersome to the patient, whether skin symptoms or GI or neurocognitive symptoms,” Dr. Akin said. “All three doses were effective; the average reduction was about 30% compared to baseline.” Specifically, 25-mg dosing showed an average 30% reduction, 50-mg dosing showed an average 19% reduction, and 100-mg dosing showed an average 35% reduction.

The researchers determined that the 25-mg daily dose was the most effective and safest, with no patients on the dose reporting grade 3 adverse events, Dr. Akin said. In total 20% and 40% of the 50- and 100-mg dose groups, respectively, reported grade 3 AEs, according to study results.* The 25-mg daily dose will be evaluated in part 2 of the trial. The trial is estimated to enroll 112 total patients, according to the ClinicalTrials.gov filing. In part 3, patients who complete parts 1 or 2, including those initially randomized to placebo, may participate in a long-term open-label extension, receiving 25 mg avapritinib plus best supportive care.

“This is targeting a population whose symptoms are not controlled by antihistamines, based on a minimum total symptom score according to diaries they fill out, and they have to be on at least two different systemic medications – antihistamine or proton-pump inhibitor and leukotriene inhibitor – and they still have significant symptoms,” Dr. Akin said. He estimated that this describes about two-thirds of his patients with indolent or smoldering systematic mastocytosis.

“This is a disease that also takes a psychological toll,” he said. “This is a problem that starts in the bone marrow; it is similar to a hematological stem-cell disorder that affects the mast cell progenitor and it’s caused by a mutation that has not been particularly targeted until this drug,” he said. While most of these patients live with a benign mastocytosis their entire lives, the symptoms can be debilitating to the point where the disease disrupts and restricts social activities and comprises their quality of life, he said.

“This is a groundbreaking therapy that will change the way we think about mastocytosis treatment going forward,” Dr. Akin said. “It’s the first time we are actually targeting the underlying mutation that’s causing the disease, in terms of reducing directly that mutation as opposed to just treating the symptoms in indolent disease.”

Scheduled session moderator Anil Nanda, MD, of the Asthma and Allergy Center in Lewisville, Texas, said the findings are encouraging. “As a practicing allergist and immunologist in the community, it is very exciting to have a potential new treatment option for indolent or smoldering systemic mastocytosis,” he said via email. “Patients appreciate new options in therapy.”

Dr. Akin, the primary investigator, receives funding from and serves as a consultant for Blueprint Medicines, which sponsored the trial. He also disclosed a financial relationship with Novartis.

SOURCE: Akin C et al. AAAAI 2020, Presentation L5.

*Correction, 4/6/2020: An earlier version of this story misstated the percentage of grade 3 adverse events. In total 20% and 40% of the 50- and 100-mg dose groups, respectively, reported grade 3 adverse events.  

A small-molecule kinase inhibitor that targets a gene mutation complicit in systemic mastocytosis has been found to reduce symptoms by about 30%, according to early results of a clinical trial scheduled to be presented at the American Academy of Allergy, Asthma, and Immunology annual meeting. The AAAAI canceled the meeting and provided abstracts and access to presenters for press coverage.

“This correlates with reduction from very severe to moderate or from moderate to mild category, and all the reductions in symptoms were statistically significant,” Cem Akin, MD, of the University of Michigan, Ann Arbor, said in an interview. He reported on part 1 of the phase 2 PIONEER trial of the kinase inhibitor avapritinib, described as a potent and highly selective inhibitor of the KIT D816V mutation that affects 90% of patients with systemic mastocytosis.

Currently, Dr. Akin noted, patients with indolent or smoldering systemic mastocytosis must rely on over-the-counter antihistamines used for seasonal allergies. “These patients use antihistamines in higher doses because mastocytosis patients have higher counts of mast cells that release histamines that cause a variety of symptoms,” he said. Symptoms, which can occur suddenly, include flushing and reactions that resemble allergic or anaphylactic reactions.

The purpose of the part 1 study was to evaluate three different dosing levels of avapritinib vs. placebo: 25, 50, and 100 mg. Ten patients were in each dosing group and nine were in the placebo group. The primary outcome was reduction in total symptom scores at 16 weeks as measured by the Indolent SM Symptom Assessment Form. “All three dose groups showed significant reductions in total symptom scores as well as specific symptoms that were most bothersome to the patient, whether skin symptoms or GI or neurocognitive symptoms,” Dr. Akin said. “All three doses were effective; the average reduction was about 30% compared to baseline.” Specifically, 25-mg dosing showed an average 30% reduction, 50-mg dosing showed an average 19% reduction, and 100-mg dosing showed an average 35% reduction.

The researchers determined that the 25-mg daily dose was the most effective and safest, with no patients on the dose reporting grade 3 adverse events, Dr. Akin said. In total 20% and 40% of the 50- and 100-mg dose groups, respectively, reported grade 3 AEs, according to study results.* The 25-mg daily dose will be evaluated in part 2 of the trial. The trial is estimated to enroll 112 total patients, according to the ClinicalTrials.gov filing. In part 3, patients who complete parts 1 or 2, including those initially randomized to placebo, may participate in a long-term open-label extension, receiving 25 mg avapritinib plus best supportive care.

“This is targeting a population whose symptoms are not controlled by antihistamines, based on a minimum total symptom score according to diaries they fill out, and they have to be on at least two different systemic medications – antihistamine or proton-pump inhibitor and leukotriene inhibitor – and they still have significant symptoms,” Dr. Akin said. He estimated that this describes about two-thirds of his patients with indolent or smoldering systematic mastocytosis.

“This is a disease that also takes a psychological toll,” he said. “This is a problem that starts in the bone marrow; it is similar to a hematological stem-cell disorder that affects the mast cell progenitor and it’s caused by a mutation that has not been particularly targeted until this drug,” he said. While most of these patients live with a benign mastocytosis their entire lives, the symptoms can be debilitating to the point where the disease disrupts and restricts social activities and comprises their quality of life, he said.

“This is a groundbreaking therapy that will change the way we think about mastocytosis treatment going forward,” Dr. Akin said. “It’s the first time we are actually targeting the underlying mutation that’s causing the disease, in terms of reducing directly that mutation as opposed to just treating the symptoms in indolent disease.”

Scheduled session moderator Anil Nanda, MD, of the Asthma and Allergy Center in Lewisville, Texas, said the findings are encouraging. “As a practicing allergist and immunologist in the community, it is very exciting to have a potential new treatment option for indolent or smoldering systemic mastocytosis,” he said via email. “Patients appreciate new options in therapy.”

Dr. Akin, the primary investigator, receives funding from and serves as a consultant for Blueprint Medicines, which sponsored the trial. He also disclosed a financial relationship with Novartis.

SOURCE: Akin C et al. AAAAI 2020, Presentation L5.

*Correction, 4/6/2020: An earlier version of this story misstated the percentage of grade 3 adverse events. In total 20% and 40% of the 50- and 100-mg dose groups, respectively, reported grade 3 adverse events.  

Infants who are hospitalized for severe bronchiolitis and receive acid-suppressant medications may be at risk of developing allergic disease by age 3 years, according to recent research released as an abstract for the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting.

The AAAAI canceled their annual meeting and provided abstracts and access to presenters for press coverage

“Among children with a history of severe bronchiolitis during infancy, exposure to acid-suppressant medications during infancy further increases the risk of developing recurrent wheeze by age 3 years,” Lacey B. Robinson, MD, of the division of rheumatology, allergy, and immunology in the department of medicine at Massachusetts General Hospital in Boston, said in an interview.

Bronchiolitis is a risk factor in infants for developing conditions such as recurrent wheeze and childhood asthma in early childhood. Acid-suppressant medications like proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) may further increase the risk of allergic disease. One study by Mitre et al. published in JAMA Pediatrics showed use of acid-suppressant medications in infants up to 6 months raised the risk of allergic disease (JAMA Pediatr. 2018;172[6]:e180315). Some studies suggest between 30% and 50% of infants diagnosed with bronchiolitis requiring hospitalization will develop asthma by age 5 years (J Allergy Clin Immunol Pract. 2017 Jan - Feb;5[1]:92-6).

“Children with severe bronchiolitis during infancy are at a high risk of developing recurrent wheeze and subsequent asthma. There is limited evidence to suggest that exposure to acid suppressant medications [such as proton pump inhibitors and histamine-2 receptor antagonists] prenatally and during early childhood increases the risk of childhood asthma,” Dr. Robinson said. “It is not known if exposure to acid suppressant medications during infancy further increases the risk of developing recurrent wheeze among high-risk children, such as in those with a history of severe bronchiolitis during infancy.”

Dr. Robinson and colleagues performed a multicenter, prospective cohort study of 921 infants who were hospitalized for severe bronchiolitis between 2011 and 2014. The investigators reviewed the medical records of the infants for acid suppressant medication use, as well as parent report of acid suppressant medication use, during an infant’s first 12 months. Overall, 879 children were analyzed after excluding for patients who developed recurrent wheeze prior to receiving acid suppressant medications, as well as patients with incomplete data. The investigators used the National Institutes of Health Guidelines for the Diagnosis and Management of Asthma (EPR-3) to define recurrent wheeze. A Cox-proportional hazard model was used to analyze the time to event, which was stratified by age and adjusted for confounders.

Infants with a history of severe bronchiolitis were at greater risk of developing recurrent wheeze by age 3 years after being exposed to acid-suppressant medications, compared with infants who were not exposed, Dr. Robinson said. Of the 879 infants in the final analysis, 159 (18%) received acid-suppressant medications, and 68 of 159 patients (43%) went on to develop recurrent wheeze, compared with 206 of 720 infants (29%) who were not exposed (unadjusted hazard ratio, 1.63; 95% confidence interval, 1.24-2.14).

After adjustment for confounders such as gender, race and ethnicity; gestational age; delivery type; severity of bronchiolitis; respiratory syncytial virus (RSV) infection status; maternal atopy; use of acid-suppressant medications during pregnancy; median household income; and insurance status, the association between recurrent wheeze and acid-suppressant medication use during infancy remained (adjusted HR, 1.54; 95% CI, 1.15-2.07).

“More research is needed on this important topic including studies in other populations,” such as in healthy children, Dr. Robinson said. “We encourage future research on this important and understudied topic, including further research on the potential underlying mechanisms of this association.”

Dr. Robinson reported no relevant financial disclosures.

SOURCE: Robinson L. AAAAI 2020, Abstract L1

Infants who are hospitalized for severe bronchiolitis and receive acid-suppressant medications may be at risk of developing allergic disease by age 3 years, according to recent research released as an abstract for the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting.

The AAAAI canceled their annual meeting and provided abstracts and access to presenters for press coverage

“Among children with a history of severe bronchiolitis during infancy, exposure to acid-suppressant medications during infancy further increases the risk of developing recurrent wheeze by age 3 years,” Lacey B. Robinson, MD, of the division of rheumatology, allergy, and immunology in the department of medicine at Massachusetts General Hospital in Boston, said in an interview.

Bronchiolitis is a risk factor in infants for developing conditions such as recurrent wheeze and childhood asthma in early childhood. Acid-suppressant medications like proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) may further increase the risk of allergic disease. One study by Mitre et al. published in JAMA Pediatrics showed use of acid-suppressant medications in infants up to 6 months raised the risk of allergic disease (JAMA Pediatr. 2018;172[6]:e180315). Some studies suggest between 30% and 50% of infants diagnosed with bronchiolitis requiring hospitalization will develop asthma by age 5 years (J Allergy Clin Immunol Pract. 2017 Jan - Feb;5[1]:92-6).

“Children with severe bronchiolitis during infancy are at a high risk of developing recurrent wheeze and subsequent asthma. There is limited evidence to suggest that exposure to acid suppressant medications [such as proton pump inhibitors and histamine-2 receptor antagonists] prenatally and during early childhood increases the risk of childhood asthma,” Dr. Robinson said. “It is not known if exposure to acid suppressant medications during infancy further increases the risk of developing recurrent wheeze among high-risk children, such as in those with a history of severe bronchiolitis during infancy.”

Dr. Robinson and colleagues performed a multicenter, prospective cohort study of 921 infants who were hospitalized for severe bronchiolitis between 2011 and 2014. The investigators reviewed the medical records of the infants for acid suppressant medication use, as well as parent report of acid suppressant medication use, during an infant’s first 12 months. Overall, 879 children were analyzed after excluding for patients who developed recurrent wheeze prior to receiving acid suppressant medications, as well as patients with incomplete data. The investigators used the National Institutes of Health Guidelines for the Diagnosis and Management of Asthma (EPR-3) to define recurrent wheeze. A Cox-proportional hazard model was used to analyze the time to event, which was stratified by age and adjusted for confounders.

Infants with a history of severe bronchiolitis were at greater risk of developing recurrent wheeze by age 3 years after being exposed to acid-suppressant medications, compared with infants who were not exposed, Dr. Robinson said. Of the 879 infants in the final analysis, 159 (18%) received acid-suppressant medications, and 68 of 159 patients (43%) went on to develop recurrent wheeze, compared with 206 of 720 infants (29%) who were not exposed (unadjusted hazard ratio, 1.63; 95% confidence interval, 1.24-2.14).

After adjustment for confounders such as gender, race and ethnicity; gestational age; delivery type; severity of bronchiolitis; respiratory syncytial virus (RSV) infection status; maternal atopy; use of acid-suppressant medications during pregnancy; median household income; and insurance status, the association between recurrent wheeze and acid-suppressant medication use during infancy remained (adjusted HR, 1.54; 95% CI, 1.15-2.07).

“More research is needed on this important topic including studies in other populations,” such as in healthy children, Dr. Robinson said. “We encourage future research on this important and understudied topic, including further research on the potential underlying mechanisms of this association.”

Dr. Robinson reported no relevant financial disclosures.

SOURCE: Robinson L. AAAAI 2020, Abstract L1

Infants who are hospitalized for severe bronchiolitis and receive acid-suppressant medications may be at risk of developing allergic disease by age 3 years, according to recent research released as an abstract for the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting.

The AAAAI canceled their annual meeting and provided abstracts and access to presenters for press coverage

“Among children with a history of severe bronchiolitis during infancy, exposure to acid-suppressant medications during infancy further increases the risk of developing recurrent wheeze by age 3 years,” Lacey B. Robinson, MD, of the division of rheumatology, allergy, and immunology in the department of medicine at Massachusetts General Hospital in Boston, said in an interview.

Bronchiolitis is a risk factor in infants for developing conditions such as recurrent wheeze and childhood asthma in early childhood. Acid-suppressant medications like proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) may further increase the risk of allergic disease. One study by Mitre et al. published in JAMA Pediatrics showed use of acid-suppressant medications in infants up to 6 months raised the risk of allergic disease (JAMA Pediatr. 2018;172[6]:e180315). Some studies suggest between 30% and 50% of infants diagnosed with bronchiolitis requiring hospitalization will develop asthma by age 5 years (J Allergy Clin Immunol Pract. 2017 Jan - Feb;5[1]:92-6).

“Children with severe bronchiolitis during infancy are at a high risk of developing recurrent wheeze and subsequent asthma. There is limited evidence to suggest that exposure to acid suppressant medications [such as proton pump inhibitors and histamine-2 receptor antagonists] prenatally and during early childhood increases the risk of childhood asthma,” Dr. Robinson said. “It is not known if exposure to acid suppressant medications during infancy further increases the risk of developing recurrent wheeze among high-risk children, such as in those with a history of severe bronchiolitis during infancy.”

Dr. Robinson and colleagues performed a multicenter, prospective cohort study of 921 infants who were hospitalized for severe bronchiolitis between 2011 and 2014. The investigators reviewed the medical records of the infants for acid suppressant medication use, as well as parent report of acid suppressant medication use, during an infant’s first 12 months. Overall, 879 children were analyzed after excluding for patients who developed recurrent wheeze prior to receiving acid suppressant medications, as well as patients with incomplete data. The investigators used the National Institutes of Health Guidelines for the Diagnosis and Management of Asthma (EPR-3) to define recurrent wheeze. A Cox-proportional hazard model was used to analyze the time to event, which was stratified by age and adjusted for confounders.

Infants with a history of severe bronchiolitis were at greater risk of developing recurrent wheeze by age 3 years after being exposed to acid-suppressant medications, compared with infants who were not exposed, Dr. Robinson said. Of the 879 infants in the final analysis, 159 (18%) received acid-suppressant medications, and 68 of 159 patients (43%) went on to develop recurrent wheeze, compared with 206 of 720 infants (29%) who were not exposed (unadjusted hazard ratio, 1.63; 95% confidence interval, 1.24-2.14).

After adjustment for confounders such as gender, race and ethnicity; gestational age; delivery type; severity of bronchiolitis; respiratory syncytial virus (RSV) infection status; maternal atopy; use of acid-suppressant medications during pregnancy; median household income; and insurance status, the association between recurrent wheeze and acid-suppressant medication use during infancy remained (adjusted HR, 1.54; 95% CI, 1.15-2.07).

“More research is needed on this important topic including studies in other populations,” such as in healthy children, Dr. Robinson said. “We encourage future research on this important and understudied topic, including further research on the potential underlying mechanisms of this association.”

Dr. Robinson reported no relevant financial disclosures.

SOURCE: Robinson L. AAAAI 2020, Abstract L1

The 2019-2020 flu paradox continues in the United States: Fewer respiratory samples are testing positive for influenza, but more people are seeking care for respiratory symptoms because of COVID-19, according to the Centers for Disease Control and Prevention.

Positive tests of respiratory samples in clinical laboratories were down to 6.9% for the week ending March 21, compared with 14.9% the week before, but outpatient visits for influenza-like illness (ILI) rose from 5.6% of all visits to 6.2% for third week of March, the CDC’s influenza division reported.

The CDC defines ILI as “fever (temperature of 100°F [37.8°C] or greater) and a cough and/or a sore throat without a known cause other than influenza.” The outpatient ILI visit rate needs to get below the national baseline of 2.4% for the CDC to call the end of the 2019-2020 flu season.

This week’s map shows that fewer states are at the highest level of ILI activity on the CDC’s 1-10 scale: 33 states plus Puerto Rico for the week ending March 21, compared with 35 and Puerto Rico the previous week. The number of states at level 10 had risen the two previous weeks, CDC data show.

“Influenza severity indicators remain moderate to low overall, but hospitalization rates differ by age group, with high rates among children and young adults,” the influenza division said.

Overall mortality also has not been high, but 155 children have died from the flu so far in 2019-2020, which is more than any season since the 2009 pandemic, the CDC noted.

[email protected]

The 2019-2020 flu paradox continues in the United States: Fewer respiratory samples are testing positive for influenza, but more people are seeking care for respiratory symptoms because of COVID-19, according to the Centers for Disease Control and Prevention.

Positive tests of respiratory samples in clinical laboratories were down to 6.9% for the week ending March 21, compared with 14.9% the week before, but outpatient visits for influenza-like illness (ILI) rose from 5.6% of all visits to 6.2% for third week of March, the CDC’s influenza division reported.

The CDC defines ILI as “fever (temperature of 100°F [37.8°C] or greater) and a cough and/or a sore throat without a known cause other than influenza.” The outpatient ILI visit rate needs to get below the national baseline of 2.4% for the CDC to call the end of the 2019-2020 flu season.

This week’s map shows that fewer states are at the highest level of ILI activity on the CDC’s 1-10 scale: 33 states plus Puerto Rico for the week ending March 21, compared with 35 and Puerto Rico the previous week. The number of states at level 10 had risen the two previous weeks, CDC data show.

“Influenza severity indicators remain moderate to low overall, but hospitalization rates differ by age group, with high rates among children and young adults,” the influenza division said.

Overall mortality also has not been high, but 155 children have died from the flu so far in 2019-2020, which is more than any season since the 2009 pandemic, the CDC noted.

[email protected]

The 2019-2020 flu paradox continues in the United States: Fewer respiratory samples are testing positive for influenza, but more people are seeking care for respiratory symptoms because of COVID-19, according to the Centers for Disease Control and Prevention.

Positive tests of respiratory samples in clinical laboratories were down to 6.9% for the week ending March 21, compared with 14.9% the week before, but outpatient visits for influenza-like illness (ILI) rose from 5.6% of all visits to 6.2% for third week of March, the CDC’s influenza division reported.

The CDC defines ILI as “fever (temperature of 100°F [37.8°C] or greater) and a cough and/or a sore throat without a known cause other than influenza.” The outpatient ILI visit rate needs to get below the national baseline of 2.4% for the CDC to call the end of the 2019-2020 flu season.

This week’s map shows that fewer states are at the highest level of ILI activity on the CDC’s 1-10 scale: 33 states plus Puerto Rico for the week ending March 21, compared with 35 and Puerto Rico the previous week. The number of states at level 10 had risen the two previous weeks, CDC data show.

“Influenza severity indicators remain moderate to low overall, but hospitalization rates differ by age group, with high rates among children and young adults,” the influenza division said.

Overall mortality also has not been high, but 155 children have died from the flu so far in 2019-2020, which is more than any season since the 2009 pandemic, the CDC noted.

[email protected]

Among patients who undergo endobronchial ultrasound-guided transbronchial biopsy using a guide sheath (EBUS-GS-TBB) for diagnosing lung cancer, cavitation and low-density areas inside the target lesion on CT and stenosis of the responsible bronchus are risk factors for infection after the procedure, according to a study published in CHEST.

“Infectious complications after [transbronchial biopsy] constitute a serious clinical problem because they might delay the start of treatment or cause the intended treatment to be modified to a milder one,” said Tomohide Souma, MD, of the department of respiratory medicine at Fujita Health University in Toyoake, Japan, and colleagues. “The precise mechanism of such complications is still unclear, and effective prophylaxis procedures have not been established. ... Thus, it is very important to identify the risk factors for infectious complications after TBB if and when these complications are to be avoided.”

To evaluate potential risk factors for infectious complications after EBUS-GS-TBB in a large sample of patients, Dr. Souma and colleagues retrospectively studied the medical records of 1,045 consecutive patients (median age, 72; 68% male) who underwent EBUS-GS-TBB between January 2013 and December 2017 at Fujita Health University Hospital.

In all, 47 patients developed infections, a cumulative incidence of about 4.5%. Infections included pneumonia (51.1%), intratumoral infection (29.8%), and three cases each of lung abscess, pleurisy, and empyema. Three patients, two with empyema and one with lung abscess, died within 1 month before administration of anticancer treatment. “In total, more than 40% of patients with post–EBUS-GS-TBB infection were unable to receive preplanned anticancer treatment,” the researchers said.

On multivariate analysis, cavitation in the lesion (odds ratio, 3.63), low-density areas in the lesion (OR, 13.26), and bronchoscopic findings of responsible bronchus stenosis (OR, 7.82) were significantly associated with development of infections post biopsy.

An analysis that matched 89 patients who received prophylactic antibiotics with controls who did not receive prophylactic antibiotics did not find that prophylactic antibiotics significantly reduced the likelihood of post–EBUS-GS-TBB infection.

“Notably, three risk factors found in our study indicate that the inflammation-prone status of lesions may be the most important factor for developing post–EBUS-TBB infection,” Dr. Souma and colleagues said. “Although our study does not rebuff the role of antibiotics in postbronchoscopy infection therapy, clinicians should notify patients that post-TBB infection may occur despite the use of prophylactic antibiotics. We recommend that careful and frequent follow-up be applied to patients undergoing diagnostic EBUS-GS-TBB with reference to the risk factors identified in our study.”

A. Christine Argento, MD, FCCP, assistant professor of medicine and thoracic surgery and director of the interventional pulmonary fellowship program at Northwestern University, Chicago, noted that this is an important study on a topic that has not been well described in the past.

[email protected]

SOURCE: Souma T et al. CHEST. 2020 Mar 4. doi: 10.1016/j.chest.2020.02.025.

Among patients who undergo endobronchial ultrasound-guided transbronchial biopsy using a guide sheath (EBUS-GS-TBB) for diagnosing lung cancer, cavitation and low-density areas inside the target lesion on CT and stenosis of the responsible bronchus are risk factors for infection after the procedure, according to a study published in CHEST.

“Infectious complications after [transbronchial biopsy] constitute a serious clinical problem because they might delay the start of treatment or cause the intended treatment to be modified to a milder one,” said Tomohide Souma, MD, of the department of respiratory medicine at Fujita Health University in Toyoake, Japan, and colleagues. “The precise mechanism of such complications is still unclear, and effective prophylaxis procedures have not been established. ... Thus, it is very important to identify the risk factors for infectious complications after TBB if and when these complications are to be avoided.”

To evaluate potential risk factors for infectious complications after EBUS-GS-TBB in a large sample of patients, Dr. Souma and colleagues retrospectively studied the medical records of 1,045 consecutive patients (median age, 72; 68% male) who underwent EBUS-GS-TBB between January 2013 and December 2017 at Fujita Health University Hospital.

In all, 47 patients developed infections, a cumulative incidence of about 4.5%. Infections included pneumonia (51.1%), intratumoral infection (29.8%), and three cases each of lung abscess, pleurisy, and empyema. Three patients, two with empyema and one with lung abscess, died within 1 month before administration of anticancer treatment. “In total, more than 40% of patients with post–EBUS-GS-TBB infection were unable to receive preplanned anticancer treatment,” the researchers said.

On multivariate analysis, cavitation in the lesion (odds ratio, 3.63), low-density areas in the lesion (OR, 13.26), and bronchoscopic findings of responsible bronchus stenosis (OR, 7.82) were significantly associated with development of infections post biopsy.

An analysis that matched 89 patients who received prophylactic antibiotics with controls who did not receive prophylactic antibiotics did not find that prophylactic antibiotics significantly reduced the likelihood of post–EBUS-GS-TBB infection.

“Notably, three risk factors found in our study indicate that the inflammation-prone status of lesions may be the most important factor for developing post–EBUS-TBB infection,” Dr. Souma and colleagues said. “Although our study does not rebuff the role of antibiotics in postbronchoscopy infection therapy, clinicians should notify patients that post-TBB infection may occur despite the use of prophylactic antibiotics. We recommend that careful and frequent follow-up be applied to patients undergoing diagnostic EBUS-GS-TBB with reference to the risk factors identified in our study.”

A. Christine Argento, MD, FCCP, assistant professor of medicine and thoracic surgery and director of the interventional pulmonary fellowship program at Northwestern University, Chicago, noted that this is an important study on a topic that has not been well described in the past.

[email protected]

SOURCE: Souma T et al. CHEST. 2020 Mar 4. doi: 10.1016/j.chest.2020.02.025.

Among patients who undergo endobronchial ultrasound-guided transbronchial biopsy using a guide sheath (EBUS-GS-TBB) for diagnosing lung cancer, cavitation and low-density areas inside the target lesion on CT and stenosis of the responsible bronchus are risk factors for infection after the procedure, according to a study published in CHEST.

“Infectious complications after [transbronchial biopsy] constitute a serious clinical problem because they might delay the start of treatment or cause the intended treatment to be modified to a milder one,” said Tomohide Souma, MD, of the department of respiratory medicine at Fujita Health University in Toyoake, Japan, and colleagues. “The precise mechanism of such complications is still unclear, and effective prophylaxis procedures have not been established. ... Thus, it is very important to identify the risk factors for infectious complications after TBB if and when these complications are to be avoided.”

To evaluate potential risk factors for infectious complications after EBUS-GS-TBB in a large sample of patients, Dr. Souma and colleagues retrospectively studied the medical records of 1,045 consecutive patients (median age, 72; 68% male) who underwent EBUS-GS-TBB between January 2013 and December 2017 at Fujita Health University Hospital.

In all, 47 patients developed infections, a cumulative incidence of about 4.5%. Infections included pneumonia (51.1%), intratumoral infection (29.8%), and three cases each of lung abscess, pleurisy, and empyema. Three patients, two with empyema and one with lung abscess, died within 1 month before administration of anticancer treatment. “In total, more than 40% of patients with post–EBUS-GS-TBB infection were unable to receive preplanned anticancer treatment,” the researchers said.

On multivariate analysis, cavitation in the lesion (odds ratio, 3.63), low-density areas in the lesion (OR, 13.26), and bronchoscopic findings of responsible bronchus stenosis (OR, 7.82) were significantly associated with development of infections post biopsy.

An analysis that matched 89 patients who received prophylactic antibiotics with controls who did not receive prophylactic antibiotics did not find that prophylactic antibiotics significantly reduced the likelihood of post–EBUS-GS-TBB infection.

“Notably, three risk factors found in our study indicate that the inflammation-prone status of lesions may be the most important factor for developing post–EBUS-TBB infection,” Dr. Souma and colleagues said. “Although our study does not rebuff the role of antibiotics in postbronchoscopy infection therapy, clinicians should notify patients that post-TBB infection may occur despite the use of prophylactic antibiotics. We recommend that careful and frequent follow-up be applied to patients undergoing diagnostic EBUS-GS-TBB with reference to the risk factors identified in our study.”

A. Christine Argento, MD, FCCP, assistant professor of medicine and thoracic surgery and director of the interventional pulmonary fellowship program at Northwestern University, Chicago, noted that this is an important study on a topic that has not been well described in the past.

[email protected]

SOURCE: Souma T et al. CHEST. 2020 Mar 4. doi: 10.1016/j.chest.2020.02.025.