Pulmonology

A small group of patients with heart failure (HF) who underwent a novel transcatheter nerve-ablation procedure seemed to benefit with improved hemodynamics, symptoms, and quality of life in an admittedly limited observational series.

All had HF with preserved ejection fraction (HFpEF) and remained on guideline-directed medical therapy during the study.

The open-label experience has launched a randomized trial, featuring a sham control group, that could ultimately challenge dogma about volume overload in patients with chronic and acute HF and the perceived essential role of diuretics.

Researchers see transvenous ablation of the right greater splanchnic nerve (GSN) as potentially appropriate for patients with HF, regardless of ventricular function or acuity. But the ongoing REBALANCE-HF trial aims to enroll up to 80 patients with chronic HFpEF.

Meanwhile, the current 18 patients with elevated resting or exertional pulmonary capillary wedge pressure (PCWP), given the procedure as part of the main trial’s “roll-in” phase, showed declines in exercise PCWP after 1 month (P = .007) and improved quality-of-life scores at both 1 and 3 months (P < .01). Also at 1 month, a third of the patients improved by at least one step in NYHA functional class.

The procedure, called splanchnic ablation for volume management (SAVM), could potentially be used “across the spectrum of acute and chronic heart failure, maybe even with reduced ejection fraction (HFrEF) and preserved ejection fraction,” Marat Fudim, MD, MHS, Duke University Medical Center, Durham, N.C., told this news organization.

However, “for outcomes, we’ve really only looked in the ambulatory setting,” and only at symptomatic and functional responses. To that extent, based on the current experience and a few small previous studies, Dr. Fudim said, SAVM seems to benefit patients with HF in general who have dyspnea at exercise. Beyond that, the kind of patient who may be most suitable for it “is something I hope we will be able answer once the randomized dataset is in.”

Dr. Fudim reported the REBALANCE-HF roll-in results at the Heart Failure Association of the European Society of Cardiology (HFA-ESC) 2022 sessions, held virtually and live in Madrid. He is also lead author on the same-day publication in the European Journal of Heart Failure.

A different treatment paradigm

Splanchnic-nerve blockade as a possible HF treatment is based on growing evidence that volume overload in patients with HF is not always the cause, at least not a main cause, of congestion and dyspnea. Rather, those classic HF signs and symptoms may often be triggered by adverse redistribution of stable fluid volume from primarily the splanchnic vascular compartment to the intrathoracic space.

In other words, what might seem like classic volume overload calling for diuresis often might actually be euvolemic redistribution of fluid from the abdomen to the chest, raising intracardiac pressures and causing dyspnea.

In that scenario, loop diuretics might only dehydrate the patient and potentially put the kidneys at risk, Dr. Fudim proposed. His recent experience with HF patients implanted with a pulmonary-artery pressure monitor, he said, suggests many who received standard volume-overload therapy had actually been normo- or hypovolemic.

More then half the patients “did not have high volume, they just had high pressures,” he said. “So there is a significant portion of the population that has pathological processes leading to high pressures, but it’s not volume overload. Diuresing those patients would probably not be the right decision.”

The unilateral SAVM procedure appears to attenuate sympathetically mediated splanchnic volume redistribution to the heart and lungs, but as it doesn’t affect the left GSN, preserves some normal sympathetic response.

Sometimes in studies of surgical or catheter-based SAVM, Dr. Fudim said, “we have observationally seen that people discontinued diuretics or decreased doses in the treatment arm.”
 

‘Beyond our classical thinking’

It’s “impressive” that such right-GSN ablation seemed to reduce exercise-filling pressures, but one should be circumspect because “it’s way beyond our classical thinking,” Wilfried Mullens, MD, PhD, Hospital Oost-Limburg, Genk, Belgium, said as a panelist after Dr. Fudim’s presentation.

“These are invasive procedures,” he noted, “and our physiological understanding does not always match up with what we’re doing in real life, if you look at other interventional procedures, like renal denervation, which showed neutral effects, or if you look at even interatrial shunt devices, which might even be dangerous.”

The field should be “very prudent” before using SAVM in practice, which shouldn’t be “before we have sufficient data to support the efficacy and safety,” Dr. Mullens said. “It remains to be seen how treatment success will be defined. Is it during exercise? How long does the treatment last? What is the effect of the treatment over time; is it not harmful? These are things that we don’t know yet.”

The procedure was considered successful in all 18 patients, 14 of whom were women and 16 of whom were in NYHA class 3. Their average age was 75, and their mean left ventricular ejection fraction (LVEF) at baseline was 61%. The primary efficacy endpoints were a reduction in PCWP at rest, with legs raised, and at 20W exercise at 1 month. Their baseline invasively measured peak exercise PCWP was at least 25 mm Hg.

At 1 month, mean PCWP at 20W exercise fell from 36.4 mm Hg to 28.9 mm Hg (P = .007) and peak PCWP declined from 39.5 mm Hg to 31.9 mm Hg (P = .013); resting PCWP wasn’t significantly affected. Twelve patients improved by at least one NYHA functional class (P = .02).

Scores on the Kansas City Cardiomyopathy Questionnaire (KCCQ), which assesses quality of life, improved by 22 points at 1 month and 18.3 points at 3 months (P < .01 for both differences).

No significant effects on 6-minute walk distance or natriuretic peptide levels were observed, nor were any observed on LVEF or echocardiographic measures of diastolic function, left ventricular (LV) atrial volume, or LV mass at 3 months.

Three “nonserious” device-related adverse events were observed, including one case of acute decompensation early in the experience, ostensibly due to excessive saline administration, Dr. Fudim reported. There was also one case of transient periprocedural hypertension and one instance of postprocedure back pain.

The SAVM procedure is performed transvenously and in general is technically “really not that challenging,” Dr. Fudim said. In most cases, the necessary skills would be accessible not only to interventional cardiologists but also heart failure specialists. “I have performed this procedure myself, and I’m a heart failure guy.”

The REBALANCE-HF roll-in phase and main trial are supported by Axon Therapies. Dr. Fudim discloses receiving support from Bayer, Bodyport, and BTG Specialty Pharmaceuticals; and consulting fees from Abbott, Audicor, Axon Therapies, Bodyguide, Bodyport, Boston Scientific, CVRx, Daxor, Edwards LifeSciences, Feldschuh Foundation, Fire1, Gradient, Intershunt, NXT Biomedical, Pharmacosmos, PreHealth, Splendo, Vironix, Viscardia, and Zoll. Dr. Mullens discloses receiving fees for speaking from Medtronic, Abbott, Novartis, Boston Scientific, AstraZeneca, and Boehringer Ingelheim.

A version of this article first appeared on Medscape.com.

A small group of patients with heart failure (HF) who underwent a novel transcatheter nerve-ablation procedure seemed to benefit with improved hemodynamics, symptoms, and quality of life in an admittedly limited observational series.

All had HF with preserved ejection fraction (HFpEF) and remained on guideline-directed medical therapy during the study.

The open-label experience has launched a randomized trial, featuring a sham control group, that could ultimately challenge dogma about volume overload in patients with chronic and acute HF and the perceived essential role of diuretics.

Researchers see transvenous ablation of the right greater splanchnic nerve (GSN) as potentially appropriate for patients with HF, regardless of ventricular function or acuity. But the ongoing REBALANCE-HF trial aims to enroll up to 80 patients with chronic HFpEF.

Meanwhile, the current 18 patients with elevated resting or exertional pulmonary capillary wedge pressure (PCWP), given the procedure as part of the main trial’s “roll-in” phase, showed declines in exercise PCWP after 1 month (P = .007) and improved quality-of-life scores at both 1 and 3 months (P < .01). Also at 1 month, a third of the patients improved by at least one step in NYHA functional class.

The procedure, called splanchnic ablation for volume management (SAVM), could potentially be used “across the spectrum of acute and chronic heart failure, maybe even with reduced ejection fraction (HFrEF) and preserved ejection fraction,” Marat Fudim, MD, MHS, Duke University Medical Center, Durham, N.C., told this news organization.

However, “for outcomes, we’ve really only looked in the ambulatory setting,” and only at symptomatic and functional responses. To that extent, based on the current experience and a few small previous studies, Dr. Fudim said, SAVM seems to benefit patients with HF in general who have dyspnea at exercise. Beyond that, the kind of patient who may be most suitable for it “is something I hope we will be able answer once the randomized dataset is in.”

Dr. Fudim reported the REBALANCE-HF roll-in results at the Heart Failure Association of the European Society of Cardiology (HFA-ESC) 2022 sessions, held virtually and live in Madrid. He is also lead author on the same-day publication in the European Journal of Heart Failure.

A different treatment paradigm

Splanchnic-nerve blockade as a possible HF treatment is based on growing evidence that volume overload in patients with HF is not always the cause, at least not a main cause, of congestion and dyspnea. Rather, those classic HF signs and symptoms may often be triggered by adverse redistribution of stable fluid volume from primarily the splanchnic vascular compartment to the intrathoracic space.

In other words, what might seem like classic volume overload calling for diuresis often might actually be euvolemic redistribution of fluid from the abdomen to the chest, raising intracardiac pressures and causing dyspnea.

In that scenario, loop diuretics might only dehydrate the patient and potentially put the kidneys at risk, Dr. Fudim proposed. His recent experience with HF patients implanted with a pulmonary-artery pressure monitor, he said, suggests many who received standard volume-overload therapy had actually been normo- or hypovolemic.

More then half the patients “did not have high volume, they just had high pressures,” he said. “So there is a significant portion of the population that has pathological processes leading to high pressures, but it’s not volume overload. Diuresing those patients would probably not be the right decision.”

The unilateral SAVM procedure appears to attenuate sympathetically mediated splanchnic volume redistribution to the heart and lungs, but as it doesn’t affect the left GSN, preserves some normal sympathetic response.

Sometimes in studies of surgical or catheter-based SAVM, Dr. Fudim said, “we have observationally seen that people discontinued diuretics or decreased doses in the treatment arm.”
 

‘Beyond our classical thinking’

It’s “impressive” that such right-GSN ablation seemed to reduce exercise-filling pressures, but one should be circumspect because “it’s way beyond our classical thinking,” Wilfried Mullens, MD, PhD, Hospital Oost-Limburg, Genk, Belgium, said as a panelist after Dr. Fudim’s presentation.

“These are invasive procedures,” he noted, “and our physiological understanding does not always match up with what we’re doing in real life, if you look at other interventional procedures, like renal denervation, which showed neutral effects, or if you look at even interatrial shunt devices, which might even be dangerous.”

The field should be “very prudent” before using SAVM in practice, which shouldn’t be “before we have sufficient data to support the efficacy and safety,” Dr. Mullens said. “It remains to be seen how treatment success will be defined. Is it during exercise? How long does the treatment last? What is the effect of the treatment over time; is it not harmful? These are things that we don’t know yet.”

The procedure was considered successful in all 18 patients, 14 of whom were women and 16 of whom were in NYHA class 3. Their average age was 75, and their mean left ventricular ejection fraction (LVEF) at baseline was 61%. The primary efficacy endpoints were a reduction in PCWP at rest, with legs raised, and at 20W exercise at 1 month. Their baseline invasively measured peak exercise PCWP was at least 25 mm Hg.

At 1 month, mean PCWP at 20W exercise fell from 36.4 mm Hg to 28.9 mm Hg (P = .007) and peak PCWP declined from 39.5 mm Hg to 31.9 mm Hg (P = .013); resting PCWP wasn’t significantly affected. Twelve patients improved by at least one NYHA functional class (P = .02).

Scores on the Kansas City Cardiomyopathy Questionnaire (KCCQ), which assesses quality of life, improved by 22 points at 1 month and 18.3 points at 3 months (P < .01 for both differences).

No significant effects on 6-minute walk distance or natriuretic peptide levels were observed, nor were any observed on LVEF or echocardiographic measures of diastolic function, left ventricular (LV) atrial volume, or LV mass at 3 months.

Three “nonserious” device-related adverse events were observed, including one case of acute decompensation early in the experience, ostensibly due to excessive saline administration, Dr. Fudim reported. There was also one case of transient periprocedural hypertension and one instance of postprocedure back pain.

The SAVM procedure is performed transvenously and in general is technically “really not that challenging,” Dr. Fudim said. In most cases, the necessary skills would be accessible not only to interventional cardiologists but also heart failure specialists. “I have performed this procedure myself, and I’m a heart failure guy.”

The REBALANCE-HF roll-in phase and main trial are supported by Axon Therapies. Dr. Fudim discloses receiving support from Bayer, Bodyport, and BTG Specialty Pharmaceuticals; and consulting fees from Abbott, Audicor, Axon Therapies, Bodyguide, Bodyport, Boston Scientific, CVRx, Daxor, Edwards LifeSciences, Feldschuh Foundation, Fire1, Gradient, Intershunt, NXT Biomedical, Pharmacosmos, PreHealth, Splendo, Vironix, Viscardia, and Zoll. Dr. Mullens discloses receiving fees for speaking from Medtronic, Abbott, Novartis, Boston Scientific, AstraZeneca, and Boehringer Ingelheim.

A version of this article first appeared on Medscape.com.

A small group of patients with heart failure (HF) who underwent a novel transcatheter nerve-ablation procedure seemed to benefit with improved hemodynamics, symptoms, and quality of life in an admittedly limited observational series.

All had HF with preserved ejection fraction (HFpEF) and remained on guideline-directed medical therapy during the study.

The open-label experience has launched a randomized trial, featuring a sham control group, that could ultimately challenge dogma about volume overload in patients with chronic and acute HF and the perceived essential role of diuretics.

Researchers see transvenous ablation of the right greater splanchnic nerve (GSN) as potentially appropriate for patients with HF, regardless of ventricular function or acuity. But the ongoing REBALANCE-HF trial aims to enroll up to 80 patients with chronic HFpEF.

Meanwhile, the current 18 patients with elevated resting or exertional pulmonary capillary wedge pressure (PCWP), given the procedure as part of the main trial’s “roll-in” phase, showed declines in exercise PCWP after 1 month (P = .007) and improved quality-of-life scores at both 1 and 3 months (P < .01). Also at 1 month, a third of the patients improved by at least one step in NYHA functional class.

The procedure, called splanchnic ablation for volume management (SAVM), could potentially be used “across the spectrum of acute and chronic heart failure, maybe even with reduced ejection fraction (HFrEF) and preserved ejection fraction,” Marat Fudim, MD, MHS, Duke University Medical Center, Durham, N.C., told this news organization.

However, “for outcomes, we’ve really only looked in the ambulatory setting,” and only at symptomatic and functional responses. To that extent, based on the current experience and a few small previous studies, Dr. Fudim said, SAVM seems to benefit patients with HF in general who have dyspnea at exercise. Beyond that, the kind of patient who may be most suitable for it “is something I hope we will be able answer once the randomized dataset is in.”

Dr. Fudim reported the REBALANCE-HF roll-in results at the Heart Failure Association of the European Society of Cardiology (HFA-ESC) 2022 sessions, held virtually and live in Madrid. He is also lead author on the same-day publication in the European Journal of Heart Failure.

A different treatment paradigm

Splanchnic-nerve blockade as a possible HF treatment is based on growing evidence that volume overload in patients with HF is not always the cause, at least not a main cause, of congestion and dyspnea. Rather, those classic HF signs and symptoms may often be triggered by adverse redistribution of stable fluid volume from primarily the splanchnic vascular compartment to the intrathoracic space.

In other words, what might seem like classic volume overload calling for diuresis often might actually be euvolemic redistribution of fluid from the abdomen to the chest, raising intracardiac pressures and causing dyspnea.

In that scenario, loop diuretics might only dehydrate the patient and potentially put the kidneys at risk, Dr. Fudim proposed. His recent experience with HF patients implanted with a pulmonary-artery pressure monitor, he said, suggests many who received standard volume-overload therapy had actually been normo- or hypovolemic.

More then half the patients “did not have high volume, they just had high pressures,” he said. “So there is a significant portion of the population that has pathological processes leading to high pressures, but it’s not volume overload. Diuresing those patients would probably not be the right decision.”

The unilateral SAVM procedure appears to attenuate sympathetically mediated splanchnic volume redistribution to the heart and lungs, but as it doesn’t affect the left GSN, preserves some normal sympathetic response.

Sometimes in studies of surgical or catheter-based SAVM, Dr. Fudim said, “we have observationally seen that people discontinued diuretics or decreased doses in the treatment arm.”
 

‘Beyond our classical thinking’

It’s “impressive” that such right-GSN ablation seemed to reduce exercise-filling pressures, but one should be circumspect because “it’s way beyond our classical thinking,” Wilfried Mullens, MD, PhD, Hospital Oost-Limburg, Genk, Belgium, said as a panelist after Dr. Fudim’s presentation.

“These are invasive procedures,” he noted, “and our physiological understanding does not always match up with what we’re doing in real life, if you look at other interventional procedures, like renal denervation, which showed neutral effects, or if you look at even interatrial shunt devices, which might even be dangerous.”

The field should be “very prudent” before using SAVM in practice, which shouldn’t be “before we have sufficient data to support the efficacy and safety,” Dr. Mullens said. “It remains to be seen how treatment success will be defined. Is it during exercise? How long does the treatment last? What is the effect of the treatment over time; is it not harmful? These are things that we don’t know yet.”

The procedure was considered successful in all 18 patients, 14 of whom were women and 16 of whom were in NYHA class 3. Their average age was 75, and their mean left ventricular ejection fraction (LVEF) at baseline was 61%. The primary efficacy endpoints were a reduction in PCWP at rest, with legs raised, and at 20W exercise at 1 month. Their baseline invasively measured peak exercise PCWP was at least 25 mm Hg.

At 1 month, mean PCWP at 20W exercise fell from 36.4 mm Hg to 28.9 mm Hg (P = .007) and peak PCWP declined from 39.5 mm Hg to 31.9 mm Hg (P = .013); resting PCWP wasn’t significantly affected. Twelve patients improved by at least one NYHA functional class (P = .02).

Scores on the Kansas City Cardiomyopathy Questionnaire (KCCQ), which assesses quality of life, improved by 22 points at 1 month and 18.3 points at 3 months (P < .01 for both differences).

No significant effects on 6-minute walk distance or natriuretic peptide levels were observed, nor were any observed on LVEF or echocardiographic measures of diastolic function, left ventricular (LV) atrial volume, or LV mass at 3 months.

Three “nonserious” device-related adverse events were observed, including one case of acute decompensation early in the experience, ostensibly due to excessive saline administration, Dr. Fudim reported. There was also one case of transient periprocedural hypertension and one instance of postprocedure back pain.

The SAVM procedure is performed transvenously and in general is technically “really not that challenging,” Dr. Fudim said. In most cases, the necessary skills would be accessible not only to interventional cardiologists but also heart failure specialists. “I have performed this procedure myself, and I’m a heart failure guy.”

The REBALANCE-HF roll-in phase and main trial are supported by Axon Therapies. Dr. Fudim discloses receiving support from Bayer, Bodyport, and BTG Specialty Pharmaceuticals; and consulting fees from Abbott, Audicor, Axon Therapies, Bodyguide, Bodyport, Boston Scientific, CVRx, Daxor, Edwards LifeSciences, Feldschuh Foundation, Fire1, Gradient, Intershunt, NXT Biomedical, Pharmacosmos, PreHealth, Splendo, Vironix, Viscardia, and Zoll. Dr. Mullens discloses receiving fees for speaking from Medtronic, Abbott, Novartis, Boston Scientific, AstraZeneca, and Boehringer Ingelheim.

A version of this article first appeared on Medscape.com.

Most COVID-19 long-haulers continue to have brain fog, fatigue, and compromised quality of life more than a year after the initial infection, results from the most extensive follow-up to date of a group of long COVID patients show.

Most patients continue to experience debilitating neurologic symptoms an average of 15 months from symptom onset, Igor Koralnik, MD, who oversees the Neuro COVID-19 Clinic at Northwestern Medicine in Chicago, said during a press briefing.

Surprisingly, in some cases, new symptoms appear that didn’t exist before, including variation of heart rate and blood pressure, and gastrointestinal symptoms, indicating there may be a late appearance in dysfunction of the autonomic nervous system in those patients, Dr. Koralnik said.

The study was published online in Annals of Clinical and Translational Neurology.
 

Evolving symptoms

The investigators evaluated the evolution of neurologic symptoms in 52 adults who had mild COVID-19 symptoms and were not admitted to the hospital.

Their mean age was 43 years, 73% were women and 77% had received a COVID-19 vaccine. These patients have now been followed for between 11 and 18 months since their initial infection.

Overall, between first and follow-up evaluations, there was no significant change in the frequency of most neurologic symptoms, including brain fog (81% vs. 71%), numbness/tingling (69% vs. 65%), headache (67% vs. 54%), dizziness (50% vs. 54%), blurred vision (34% vs. 44%), tinnitus (33% vs. 42%), and fatigue (87% vs. 81%).

The only neurologic symptoms that decreased over time were loss of taste (63% vs. 27%) and smell (58% vs. 21%).

Conversely, heart rate and blood pressure variation (35% vs. 56%) and gastrointestinal symptoms (27% vs. 48%; P = .04) increased at follow-up evaluations.

Patients reported subjective improvements in their recovery, cognitive function and fatigue, but quality of life measures remained lower than the average population of the United States.

There was a neutral effect of COVID vaccination on long COVID symptoms – it didn’t cure long COVID or make long COVID worse, which is a reason given by some long-haulers for not getting vaccinated, Dr. Koralnik told the briefing.

Therefore, “we continue to encourage our patients to get vaccinated and boosted according to the Centers for Disease Control and Prevention recommendation,” he said.
 

Escape from the ‘pit of despair’

To date, the Northwestern Medicine Neuro COVID-19 Clinic has treated nearly 1,400 COVID long-haulers from across the United States.

Emily Caffee, a physical therapist from Wheaton, Ill., is one of them.

Speaking at the briefing, the 36-year-old described her saga and roller coaster of recovering from long COVID in three acts: her initial infection, followed by a descent into a pit of physical and emotional despair, followed by her eventual escape from that pit more than two years later.

Following a fairly mild case of COVID, Ms. Caffee said worsening neurologic symptoms forced her to take medical leave from her very physical and cognitively demanding job. 

Ms. Caffee said she experienced crushing fatigue and brain fog, as well as rapid heart rate and blood pressure changes going from sitting to standing position.

She went from being a competitive athlete to someone who could barely get off the couch or empty the dishwasher.

With the ongoing help of her medical team, she slowly returned to daily activities and eventually to work on a limited basis.

Today, Ms. Caffee says she’s 90%-95% better but still she has some lingering symptoms and does not yet feel like her pre-COVID self.

It’s been a very slow climb out of the pit, Ms. Caffee said.

This study has no specific funding. The authors disclosed no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

Most COVID-19 long-haulers continue to have brain fog, fatigue, and compromised quality of life more than a year after the initial infection, results from the most extensive follow-up to date of a group of long COVID patients show.

Most patients continue to experience debilitating neurologic symptoms an average of 15 months from symptom onset, Igor Koralnik, MD, who oversees the Neuro COVID-19 Clinic at Northwestern Medicine in Chicago, said during a press briefing.

Surprisingly, in some cases, new symptoms appear that didn’t exist before, including variation of heart rate and blood pressure, and gastrointestinal symptoms, indicating there may be a late appearance in dysfunction of the autonomic nervous system in those patients, Dr. Koralnik said.

The study was published online in Annals of Clinical and Translational Neurology.
 

Evolving symptoms

The investigators evaluated the evolution of neurologic symptoms in 52 adults who had mild COVID-19 symptoms and were not admitted to the hospital.

Their mean age was 43 years, 73% were women and 77% had received a COVID-19 vaccine. These patients have now been followed for between 11 and 18 months since their initial infection.

Overall, between first and follow-up evaluations, there was no significant change in the frequency of most neurologic symptoms, including brain fog (81% vs. 71%), numbness/tingling (69% vs. 65%), headache (67% vs. 54%), dizziness (50% vs. 54%), blurred vision (34% vs. 44%), tinnitus (33% vs. 42%), and fatigue (87% vs. 81%).

The only neurologic symptoms that decreased over time were loss of taste (63% vs. 27%) and smell (58% vs. 21%).

Conversely, heart rate and blood pressure variation (35% vs. 56%) and gastrointestinal symptoms (27% vs. 48%; P = .04) increased at follow-up evaluations.

Patients reported subjective improvements in their recovery, cognitive function and fatigue, but quality of life measures remained lower than the average population of the United States.

There was a neutral effect of COVID vaccination on long COVID symptoms – it didn’t cure long COVID or make long COVID worse, which is a reason given by some long-haulers for not getting vaccinated, Dr. Koralnik told the briefing.

Therefore, “we continue to encourage our patients to get vaccinated and boosted according to the Centers for Disease Control and Prevention recommendation,” he said.
 

Escape from the ‘pit of despair’

To date, the Northwestern Medicine Neuro COVID-19 Clinic has treated nearly 1,400 COVID long-haulers from across the United States.

Emily Caffee, a physical therapist from Wheaton, Ill., is one of them.

Speaking at the briefing, the 36-year-old described her saga and roller coaster of recovering from long COVID in three acts: her initial infection, followed by a descent into a pit of physical and emotional despair, followed by her eventual escape from that pit more than two years later.

Following a fairly mild case of COVID, Ms. Caffee said worsening neurologic symptoms forced her to take medical leave from her very physical and cognitively demanding job. 

Ms. Caffee said she experienced crushing fatigue and brain fog, as well as rapid heart rate and blood pressure changes going from sitting to standing position.

She went from being a competitive athlete to someone who could barely get off the couch or empty the dishwasher.

With the ongoing help of her medical team, she slowly returned to daily activities and eventually to work on a limited basis.

Today, Ms. Caffee says she’s 90%-95% better but still she has some lingering symptoms and does not yet feel like her pre-COVID self.

It’s been a very slow climb out of the pit, Ms. Caffee said.

This study has no specific funding. The authors disclosed no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

Most COVID-19 long-haulers continue to have brain fog, fatigue, and compromised quality of life more than a year after the initial infection, results from the most extensive follow-up to date of a group of long COVID patients show.

Most patients continue to experience debilitating neurologic symptoms an average of 15 months from symptom onset, Igor Koralnik, MD, who oversees the Neuro COVID-19 Clinic at Northwestern Medicine in Chicago, said during a press briefing.

Surprisingly, in some cases, new symptoms appear that didn’t exist before, including variation of heart rate and blood pressure, and gastrointestinal symptoms, indicating there may be a late appearance in dysfunction of the autonomic nervous system in those patients, Dr. Koralnik said.

The study was published online in Annals of Clinical and Translational Neurology.
 

Evolving symptoms

The investigators evaluated the evolution of neurologic symptoms in 52 adults who had mild COVID-19 symptoms and were not admitted to the hospital.

Their mean age was 43 years, 73% were women and 77% had received a COVID-19 vaccine. These patients have now been followed for between 11 and 18 months since their initial infection.

Overall, between first and follow-up evaluations, there was no significant change in the frequency of most neurologic symptoms, including brain fog (81% vs. 71%), numbness/tingling (69% vs. 65%), headache (67% vs. 54%), dizziness (50% vs. 54%), blurred vision (34% vs. 44%), tinnitus (33% vs. 42%), and fatigue (87% vs. 81%).

The only neurologic symptoms that decreased over time were loss of taste (63% vs. 27%) and smell (58% vs. 21%).

Conversely, heart rate and blood pressure variation (35% vs. 56%) and gastrointestinal symptoms (27% vs. 48%; P = .04) increased at follow-up evaluations.

Patients reported subjective improvements in their recovery, cognitive function and fatigue, but quality of life measures remained lower than the average population of the United States.

There was a neutral effect of COVID vaccination on long COVID symptoms – it didn’t cure long COVID or make long COVID worse, which is a reason given by some long-haulers for not getting vaccinated, Dr. Koralnik told the briefing.

Therefore, “we continue to encourage our patients to get vaccinated and boosted according to the Centers for Disease Control and Prevention recommendation,” he said.
 

Escape from the ‘pit of despair’

To date, the Northwestern Medicine Neuro COVID-19 Clinic has treated nearly 1,400 COVID long-haulers from across the United States.

Emily Caffee, a physical therapist from Wheaton, Ill., is one of them.

Speaking at the briefing, the 36-year-old described her saga and roller coaster of recovering from long COVID in three acts: her initial infection, followed by a descent into a pit of physical and emotional despair, followed by her eventual escape from that pit more than two years later.

Following a fairly mild case of COVID, Ms. Caffee said worsening neurologic symptoms forced her to take medical leave from her very physical and cognitively demanding job. 

Ms. Caffee said she experienced crushing fatigue and brain fog, as well as rapid heart rate and blood pressure changes going from sitting to standing position.

She went from being a competitive athlete to someone who could barely get off the couch or empty the dishwasher.

With the ongoing help of her medical team, she slowly returned to daily activities and eventually to work on a limited basis.

Today, Ms. Caffee says she’s 90%-95% better but still she has some lingering symptoms and does not yet feel like her pre-COVID self.

It’s been a very slow climb out of the pit, Ms. Caffee said.

This study has no specific funding. The authors disclosed no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

Sildenafil (Viagra, Pfizer), a phosphodieterase-5 (PDE-5) inhibitor and a pulmonary-selective vasodilator, may reduce mortality in patients with idiopathic pulmonary fibrosis (IPF), compared with placebo or standard of care but it does not reduce hospitalizations or acute exacerbations from the disorder, a small meta-analysis suggests.

“There have only been four trials investigating sildenafil [in IPF] and the results were very close to being statistically significant so the addition of a few events would cause that to be true,” Tyler Pitre, MD, McMaster University, Hamilton, Ont., and Dena Zeraatkar, PhD, Harvard Medical School, Boston, told this news organization in a joint email.

“So lack of statistical significance does not preclude benefit,” they added, “and we think these results warrant additional trials and, if results remain consistent, [we] suspect the next update of the analysis may demonstrate statistical significance.”

The study was published online in Pulmonary Pharmacology & Therapeutics.
 

Reanalysis necessary

As the investigators pointed out, the most recent international guidelines have a conditional recommendation against the use of sildenafil in IPF patients so reanalysis of the data was felt to be necessary in order to inform upcoming guidelines. The purpose of the review was to provide an update of the evidence as to whether sildenafil not only provides mortality benefit in this patient population but also whether it improves overall lung function, reduces exacerbations and hospitalizations along with adverse events (AEs) leading to drug discontinuation.

The four studies included in the meta-analysis were all randomized, controlled trials in which either standalone PDE-5 inhibitors were compared with placebo or with standard IPF care with either pirfenidone (Esbroef ) or nintedanib (Ofev). The age of participants across the trials ranged from 68.6 years to 70.4 years and participants were predominantly male.

Follow-up ranged from just 12 weeks to 52 weeks. “Four trials including 659 patients and 88 deaths, reported on mortality,” the investigators noted. At a relative risk reduction of 0.73 (95% confidence interval, 0.51-1.04), the investigators concluded with moderate certainty that sildenafil probably reduces mortality in IPF patients.

Four trials including 659 patients reported on acute exacerbations and hospitalizations. At a RR of 1.10 (95% CI, 0.61-1.67), pooled results showed sildenafil may not reduce hospitalizations or acute exacerbations, compared with controls, although this conclusion was reached with low certainty. Four trials containing slightly more patients at 661 participants reported on AEs leading to drug discontinuation.

Again with moderate certainty, the authors concluded there is probably no difference in drug discontinuation rates because of AEs when comparing sildenafil to controls, at a RR of 0.79 (95% CI, 0.56-1.10). Four trials including 602 patients reported on lung function changes while diffusion capacity of carbon monoxide (DLCO) results were available for 487 patients. Based on these four trials, sildenafil may not change the decline of forced vital capacity (FVC) at a mean difference of 0.61% (95% CI, –0.29 to 1.59), compared with standard of care or placebo.

Nor may it change the rate of DLCO decline at a MD of 0.97 (95% CI, 0.04-1.90), both outcomes again being rated with moderate certainty. Asked if the combination of either nintedanib plus sildenafil or pirfenidone plus sildenafil led to a mortality benefit in IPF patients, Dr. Pitre and Dr. Zeraatkar noted that there was no mortality benefit in either the INSTAGE trial or in another recent study published in Lancet Respiratory Medicine.

“However, both of these trials were quite small and therefore unlikely to detect a mortality benefit,” Dr. Pitre and Dr. Zeraatkar noted. Indeed, the benefit of doing a systematic review is the ability to pool event rates across trials to see if a benefit emerges as well as to evaluate the consistency of the direction of these effects.

“Our review presented the most up-to-date and comprehensive summary of the evidence on sildenafil therapy for IPF patients,” the authors stated.

While they did acknowledge that the mortality benefit seen with sildenafil over placebo or standard of care did not reach statistical significance, this was likely because of too few patients and events. For example, in a systematic review published in the New England Journal of Medicine in 1988, the authors were able to show a statistically significant benefit on 5-year mortality risk with the combination of tamoxifen and cytotoxic therapy whereas none of the individual trials analyzed were able to detect a mortality benefit because they were underpowered.

“Similarly, we suggest that something like this is possible with sildenafil, as the three major trials addressing sildenafil show the same direction toward benefit with little inconsistency,” Dr. Pitre and Dr. Zeraatkar noted.

“We should not exclude benefits based on P values alone,” they said, adding: “Clearly out systematic review is not going to change clinical practice given the uncertainty of the results but I do think that in a disease such as IPF, further research is warranted in targeted patient populations [and] for clinicians, we suggest they keep an open mind to sildenafil.”

Commentary

Asked to comment on the findings, Krishna Thavarajah, MD, director of the interstitial lung disease program at Henry Ford Hospital and clinical assistant professor at Wayne State University, both in Detroit, agreed with the authors that the lack of a statistically significant mortality benefit seen in the meta-analysis does not necessarily translate into a lack of benefit from the use of sildenafil in IPF patients. “As the authors point out, there are simply not enough data available to know if there is a mortality benefit, limited by the variable follow-up times and IPF patients targeted with or without pulmonary hypertension.”

Indeed, Dr. Thavarajah felt that a mortality benefit might be difficult to show in IPF patients, especially those on antifibrotics, given the duration of the studies analyzed and the number of patients needed to be able to show a statistically significant difference. “I myself have not prescribed sildenafil for IPF patients given the lack of clear data,” Dr. Thavarajah acknowledged.

“[But] the meta-analysis shows that sildenafil could have a mortality benefit in IPF patients without evidence of a benefit in FVC, DLCO, or acute exacerbations,” she confirmed, agreeing that further study would be helpful in assessing the potential for sildenafil to provide a mortality benefit in IPF patients.

No funding for the study was reported. Neither the authors nor Dr. Thavarajah had any conflicts of interest to declare.

Sildenafil (Viagra, Pfizer), a phosphodieterase-5 (PDE-5) inhibitor and a pulmonary-selective vasodilator, may reduce mortality in patients with idiopathic pulmonary fibrosis (IPF), compared with placebo or standard of care but it does not reduce hospitalizations or acute exacerbations from the disorder, a small meta-analysis suggests.

“There have only been four trials investigating sildenafil [in IPF] and the results were very close to being statistically significant so the addition of a few events would cause that to be true,” Tyler Pitre, MD, McMaster University, Hamilton, Ont., and Dena Zeraatkar, PhD, Harvard Medical School, Boston, told this news organization in a joint email.

“So lack of statistical significance does not preclude benefit,” they added, “and we think these results warrant additional trials and, if results remain consistent, [we] suspect the next update of the analysis may demonstrate statistical significance.”

The study was published online in Pulmonary Pharmacology & Therapeutics.
 

Reanalysis necessary

As the investigators pointed out, the most recent international guidelines have a conditional recommendation against the use of sildenafil in IPF patients so reanalysis of the data was felt to be necessary in order to inform upcoming guidelines. The purpose of the review was to provide an update of the evidence as to whether sildenafil not only provides mortality benefit in this patient population but also whether it improves overall lung function, reduces exacerbations and hospitalizations along with adverse events (AEs) leading to drug discontinuation.

The four studies included in the meta-analysis were all randomized, controlled trials in which either standalone PDE-5 inhibitors were compared with placebo or with standard IPF care with either pirfenidone (Esbroef ) or nintedanib (Ofev). The age of participants across the trials ranged from 68.6 years to 70.4 years and participants were predominantly male.

Follow-up ranged from just 12 weeks to 52 weeks. “Four trials including 659 patients and 88 deaths, reported on mortality,” the investigators noted. At a relative risk reduction of 0.73 (95% confidence interval, 0.51-1.04), the investigators concluded with moderate certainty that sildenafil probably reduces mortality in IPF patients.

Four trials including 659 patients reported on acute exacerbations and hospitalizations. At a RR of 1.10 (95% CI, 0.61-1.67), pooled results showed sildenafil may not reduce hospitalizations or acute exacerbations, compared with controls, although this conclusion was reached with low certainty. Four trials containing slightly more patients at 661 participants reported on AEs leading to drug discontinuation.

Again with moderate certainty, the authors concluded there is probably no difference in drug discontinuation rates because of AEs when comparing sildenafil to controls, at a RR of 0.79 (95% CI, 0.56-1.10). Four trials including 602 patients reported on lung function changes while diffusion capacity of carbon monoxide (DLCO) results were available for 487 patients. Based on these four trials, sildenafil may not change the decline of forced vital capacity (FVC) at a mean difference of 0.61% (95% CI, –0.29 to 1.59), compared with standard of care or placebo.

Nor may it change the rate of DLCO decline at a MD of 0.97 (95% CI, 0.04-1.90), both outcomes again being rated with moderate certainty. Asked if the combination of either nintedanib plus sildenafil or pirfenidone plus sildenafil led to a mortality benefit in IPF patients, Dr. Pitre and Dr. Zeraatkar noted that there was no mortality benefit in either the INSTAGE trial or in another recent study published in Lancet Respiratory Medicine.

“However, both of these trials were quite small and therefore unlikely to detect a mortality benefit,” Dr. Pitre and Dr. Zeraatkar noted. Indeed, the benefit of doing a systematic review is the ability to pool event rates across trials to see if a benefit emerges as well as to evaluate the consistency of the direction of these effects.

“Our review presented the most up-to-date and comprehensive summary of the evidence on sildenafil therapy for IPF patients,” the authors stated.

While they did acknowledge that the mortality benefit seen with sildenafil over placebo or standard of care did not reach statistical significance, this was likely because of too few patients and events. For example, in a systematic review published in the New England Journal of Medicine in 1988, the authors were able to show a statistically significant benefit on 5-year mortality risk with the combination of tamoxifen and cytotoxic therapy whereas none of the individual trials analyzed were able to detect a mortality benefit because they were underpowered.

“Similarly, we suggest that something like this is possible with sildenafil, as the three major trials addressing sildenafil show the same direction toward benefit with little inconsistency,” Dr. Pitre and Dr. Zeraatkar noted.

“We should not exclude benefits based on P values alone,” they said, adding: “Clearly out systematic review is not going to change clinical practice given the uncertainty of the results but I do think that in a disease such as IPF, further research is warranted in targeted patient populations [and] for clinicians, we suggest they keep an open mind to sildenafil.”

Commentary

Asked to comment on the findings, Krishna Thavarajah, MD, director of the interstitial lung disease program at Henry Ford Hospital and clinical assistant professor at Wayne State University, both in Detroit, agreed with the authors that the lack of a statistically significant mortality benefit seen in the meta-analysis does not necessarily translate into a lack of benefit from the use of sildenafil in IPF patients. “As the authors point out, there are simply not enough data available to know if there is a mortality benefit, limited by the variable follow-up times and IPF patients targeted with or without pulmonary hypertension.”

Indeed, Dr. Thavarajah felt that a mortality benefit might be difficult to show in IPF patients, especially those on antifibrotics, given the duration of the studies analyzed and the number of patients needed to be able to show a statistically significant difference. “I myself have not prescribed sildenafil for IPF patients given the lack of clear data,” Dr. Thavarajah acknowledged.

“[But] the meta-analysis shows that sildenafil could have a mortality benefit in IPF patients without evidence of a benefit in FVC, DLCO, or acute exacerbations,” she confirmed, agreeing that further study would be helpful in assessing the potential for sildenafil to provide a mortality benefit in IPF patients.

No funding for the study was reported. Neither the authors nor Dr. Thavarajah had any conflicts of interest to declare.

Sildenafil (Viagra, Pfizer), a phosphodieterase-5 (PDE-5) inhibitor and a pulmonary-selective vasodilator, may reduce mortality in patients with idiopathic pulmonary fibrosis (IPF), compared with placebo or standard of care but it does not reduce hospitalizations or acute exacerbations from the disorder, a small meta-analysis suggests.

“There have only been four trials investigating sildenafil [in IPF] and the results were very close to being statistically significant so the addition of a few events would cause that to be true,” Tyler Pitre, MD, McMaster University, Hamilton, Ont., and Dena Zeraatkar, PhD, Harvard Medical School, Boston, told this news organization in a joint email.

“So lack of statistical significance does not preclude benefit,” they added, “and we think these results warrant additional trials and, if results remain consistent, [we] suspect the next update of the analysis may demonstrate statistical significance.”

The study was published online in Pulmonary Pharmacology & Therapeutics.
 

Reanalysis necessary

As the investigators pointed out, the most recent international guidelines have a conditional recommendation against the use of sildenafil in IPF patients so reanalysis of the data was felt to be necessary in order to inform upcoming guidelines. The purpose of the review was to provide an update of the evidence as to whether sildenafil not only provides mortality benefit in this patient population but also whether it improves overall lung function, reduces exacerbations and hospitalizations along with adverse events (AEs) leading to drug discontinuation.

The four studies included in the meta-analysis were all randomized, controlled trials in which either standalone PDE-5 inhibitors were compared with placebo or with standard IPF care with either pirfenidone (Esbroef ) or nintedanib (Ofev). The age of participants across the trials ranged from 68.6 years to 70.4 years and participants were predominantly male.

Follow-up ranged from just 12 weeks to 52 weeks. “Four trials including 659 patients and 88 deaths, reported on mortality,” the investigators noted. At a relative risk reduction of 0.73 (95% confidence interval, 0.51-1.04), the investigators concluded with moderate certainty that sildenafil probably reduces mortality in IPF patients.

Four trials including 659 patients reported on acute exacerbations and hospitalizations. At a RR of 1.10 (95% CI, 0.61-1.67), pooled results showed sildenafil may not reduce hospitalizations or acute exacerbations, compared with controls, although this conclusion was reached with low certainty. Four trials containing slightly more patients at 661 participants reported on AEs leading to drug discontinuation.

Again with moderate certainty, the authors concluded there is probably no difference in drug discontinuation rates because of AEs when comparing sildenafil to controls, at a RR of 0.79 (95% CI, 0.56-1.10). Four trials including 602 patients reported on lung function changes while diffusion capacity of carbon monoxide (DLCO) results were available for 487 patients. Based on these four trials, sildenafil may not change the decline of forced vital capacity (FVC) at a mean difference of 0.61% (95% CI, –0.29 to 1.59), compared with standard of care or placebo.

Nor may it change the rate of DLCO decline at a MD of 0.97 (95% CI, 0.04-1.90), both outcomes again being rated with moderate certainty. Asked if the combination of either nintedanib plus sildenafil or pirfenidone plus sildenafil led to a mortality benefit in IPF patients, Dr. Pitre and Dr. Zeraatkar noted that there was no mortality benefit in either the INSTAGE trial or in another recent study published in Lancet Respiratory Medicine.

“However, both of these trials were quite small and therefore unlikely to detect a mortality benefit,” Dr. Pitre and Dr. Zeraatkar noted. Indeed, the benefit of doing a systematic review is the ability to pool event rates across trials to see if a benefit emerges as well as to evaluate the consistency of the direction of these effects.

“Our review presented the most up-to-date and comprehensive summary of the evidence on sildenafil therapy for IPF patients,” the authors stated.

While they did acknowledge that the mortality benefit seen with sildenafil over placebo or standard of care did not reach statistical significance, this was likely because of too few patients and events. For example, in a systematic review published in the New England Journal of Medicine in 1988, the authors were able to show a statistically significant benefit on 5-year mortality risk with the combination of tamoxifen and cytotoxic therapy whereas none of the individual trials analyzed were able to detect a mortality benefit because they were underpowered.

“Similarly, we suggest that something like this is possible with sildenafil, as the three major trials addressing sildenafil show the same direction toward benefit with little inconsistency,” Dr. Pitre and Dr. Zeraatkar noted.

“We should not exclude benefits based on P values alone,” they said, adding: “Clearly out systematic review is not going to change clinical practice given the uncertainty of the results but I do think that in a disease such as IPF, further research is warranted in targeted patient populations [and] for clinicians, we suggest they keep an open mind to sildenafil.”

Commentary

Asked to comment on the findings, Krishna Thavarajah, MD, director of the interstitial lung disease program at Henry Ford Hospital and clinical assistant professor at Wayne State University, both in Detroit, agreed with the authors that the lack of a statistically significant mortality benefit seen in the meta-analysis does not necessarily translate into a lack of benefit from the use of sildenafil in IPF patients. “As the authors point out, there are simply not enough data available to know if there is a mortality benefit, limited by the variable follow-up times and IPF patients targeted with or without pulmonary hypertension.”

Indeed, Dr. Thavarajah felt that a mortality benefit might be difficult to show in IPF patients, especially those on antifibrotics, given the duration of the studies analyzed and the number of patients needed to be able to show a statistically significant difference. “I myself have not prescribed sildenafil for IPF patients given the lack of clear data,” Dr. Thavarajah acknowledged.

“[But] the meta-analysis shows that sildenafil could have a mortality benefit in IPF patients without evidence of a benefit in FVC, DLCO, or acute exacerbations,” she confirmed, agreeing that further study would be helpful in assessing the potential for sildenafil to provide a mortality benefit in IPF patients.

No funding for the study was reported. Neither the authors nor Dr. Thavarajah had any conflicts of interest to declare.

A study shows that, over a 4-year period, 15 teenagers were injured from exploding e-cigarettes, according to surgeons who have treated young people at nine hospitals in the United States.

“It definitely was an injury we were seeing frequently,” Shannon Acker, MD, an assistant professor of pediatric surgery at the University of Colorado at Denver, Aurora, and a pediatric surgeon at Children’s Hospital Colorado, said in a statement.

Reporting in the Journal of Surgical Research, doctors detail injuries from e-cigarette explosions from January 2016 through December 2019. Ten teens were hospitalized, including three who were admitted to ICUs.

“When we think about e-cigarettes, vaping, and the problems of marketing cigarettes to teenagers, it usually has to do with addiction and lung injury,” said Dr. Acker, a coauthor of the new study. “Whereas we, as trauma surgeons, were seeing these other traumatic injuries.”

Six of the teens had facial burns, five of them lost multiple teeth, five had burns around the thighs and groin, four burned their hands, and four burned their eyes. One teen injured their radial nerve, which runs through the arm. Another cut their face, and one fractured their jaw.

Overall, six teens needed surgery, including one who needed multiple operations for a severe hand injury.

Three of the teenagers had never used e-cigarettes before the day they were hurt.

Vaping has become far more common than smoking traditional cigarettes among U.S. teens in recent years. More than 2 million of them currently use e-cigarettes, according to the Food and Drug Administration, including more than 11% of high school students and almost 3% of middle schoolers.

Most e-cigarettes contain nicotine, which is highly addictive and can impair healthy brain development in adolescents, according to the CDC. Other chemicals and flavorings in the liquids that are heated during vaping can also damage the lungs. Fires and explosions, while rare, are also a risk that’s been previously documented by the FDA, the Centers for Disease Control and Prevention, and the Federal Emergency Management Agency.

Nationwide, there were 195 reported explosions and fires involving e-cigarettes in all ages between 2009 and 2016, according to a FEMA report. While no deaths were reported, 29% of these cases involved severe injuries.

“The shape and construction of electronic cigarettes” can make them behave like “flaming rockets when a battery fails,” according to FEMA.

Vaping devices typically use a rechargeable lithium-ion battery that vaporizes the liquid nicotine solution, Dr. Acker said. “They are not highly regulated, and the batteries may be of inferior quality and prone to explosion.”

A version of this article first appeared on WebMD.com.

A study shows that, over a 4-year period, 15 teenagers were injured from exploding e-cigarettes, according to surgeons who have treated young people at nine hospitals in the United States.

“It definitely was an injury we were seeing frequently,” Shannon Acker, MD, an assistant professor of pediatric surgery at the University of Colorado at Denver, Aurora, and a pediatric surgeon at Children’s Hospital Colorado, said in a statement.

Reporting in the Journal of Surgical Research, doctors detail injuries from e-cigarette explosions from January 2016 through December 2019. Ten teens were hospitalized, including three who were admitted to ICUs.

“When we think about e-cigarettes, vaping, and the problems of marketing cigarettes to teenagers, it usually has to do with addiction and lung injury,” said Dr. Acker, a coauthor of the new study. “Whereas we, as trauma surgeons, were seeing these other traumatic injuries.”

Six of the teens had facial burns, five of them lost multiple teeth, five had burns around the thighs and groin, four burned their hands, and four burned their eyes. One teen injured their radial nerve, which runs through the arm. Another cut their face, and one fractured their jaw.

Overall, six teens needed surgery, including one who needed multiple operations for a severe hand injury.

Three of the teenagers had never used e-cigarettes before the day they were hurt.

Vaping has become far more common than smoking traditional cigarettes among U.S. teens in recent years. More than 2 million of them currently use e-cigarettes, according to the Food and Drug Administration, including more than 11% of high school students and almost 3% of middle schoolers.

Most e-cigarettes contain nicotine, which is highly addictive and can impair healthy brain development in adolescents, according to the CDC. Other chemicals and flavorings in the liquids that are heated during vaping can also damage the lungs. Fires and explosions, while rare, are also a risk that’s been previously documented by the FDA, the Centers for Disease Control and Prevention, and the Federal Emergency Management Agency.

Nationwide, there were 195 reported explosions and fires involving e-cigarettes in all ages between 2009 and 2016, according to a FEMA report. While no deaths were reported, 29% of these cases involved severe injuries.

“The shape and construction of electronic cigarettes” can make them behave like “flaming rockets when a battery fails,” according to FEMA.

Vaping devices typically use a rechargeable lithium-ion battery that vaporizes the liquid nicotine solution, Dr. Acker said. “They are not highly regulated, and the batteries may be of inferior quality and prone to explosion.”

A version of this article first appeared on WebMD.com.

A study shows that, over a 4-year period, 15 teenagers were injured from exploding e-cigarettes, according to surgeons who have treated young people at nine hospitals in the United States.

“It definitely was an injury we were seeing frequently,” Shannon Acker, MD, an assistant professor of pediatric surgery at the University of Colorado at Denver, Aurora, and a pediatric surgeon at Children’s Hospital Colorado, said in a statement.

Reporting in the Journal of Surgical Research, doctors detail injuries from e-cigarette explosions from January 2016 through December 2019. Ten teens were hospitalized, including three who were admitted to ICUs.

“When we think about e-cigarettes, vaping, and the problems of marketing cigarettes to teenagers, it usually has to do with addiction and lung injury,” said Dr. Acker, a coauthor of the new study. “Whereas we, as trauma surgeons, were seeing these other traumatic injuries.”

Six of the teens had facial burns, five of them lost multiple teeth, five had burns around the thighs and groin, four burned their hands, and four burned their eyes. One teen injured their radial nerve, which runs through the arm. Another cut their face, and one fractured their jaw.

Overall, six teens needed surgery, including one who needed multiple operations for a severe hand injury.

Three of the teenagers had never used e-cigarettes before the day they were hurt.

Vaping has become far more common than smoking traditional cigarettes among U.S. teens in recent years. More than 2 million of them currently use e-cigarettes, according to the Food and Drug Administration, including more than 11% of high school students and almost 3% of middle schoolers.

Most e-cigarettes contain nicotine, which is highly addictive and can impair healthy brain development in adolescents, according to the CDC. Other chemicals and flavorings in the liquids that are heated during vaping can also damage the lungs. Fires and explosions, while rare, are also a risk that’s been previously documented by the FDA, the Centers for Disease Control and Prevention, and the Federal Emergency Management Agency.

Nationwide, there were 195 reported explosions and fires involving e-cigarettes in all ages between 2009 and 2016, according to a FEMA report. While no deaths were reported, 29% of these cases involved severe injuries.

“The shape and construction of electronic cigarettes” can make them behave like “flaming rockets when a battery fails,” according to FEMA.

Vaping devices typically use a rechargeable lithium-ion battery that vaporizes the liquid nicotine solution, Dr. Acker said. “They are not highly regulated, and the batteries may be of inferior quality and prone to explosion.”

A version of this article first appeared on WebMD.com.

The diverse effects of obesity on lung health and disease are increasingly being teased apart, with researchers honing in on the impact of metabolic dysfunction, circulating inflammatory factors produced by adipose tissue, lipid handling, and other factors – in addition to body mass index – that are associated with the obese state.

“The bird’s eye view is that obesity completely changes lung health. It’s something we’ve only recently begun to appreciate,” said Anne E. Dixon, MA, BM, BCh, director of the Vermont Lung Center at the University of Vermont, Burlington, who is focused on the research field of obesity and lung disease.

OSA and OHS

“With sleep apnea we tend to focus on anatomic considerations, but there may be relationships or interactions between obesity and neuromuscular function and neuroventilatory control,” Susheel P. Patil, MD, PhD, director of the sleep medicine program for University Hospitals and assistant professor at Case Western Reserve University, Cleveland, said in an interview.

Some studies suggest, for instance, that TNF-alpha can increase obstructive sleep apnea (OSA) susceptibility and severity through its neuroventilatory modulating properties during sleep. And the potential for additional proinflammatory cytokines produced by adipose tissue to similarly affect upper airway neuroventilatory control is an “intriguing line” of inquiry for researchers in the sleep apnea space, he said.

Leptin is of interest particularly in obesity hypoventilation syndrome (OHS), which is characterized by chronic daytime hypercapnia. Best known as a satiety hormone, leptin is produced by adipose tissue and suppresses appetite at the central nervous system level. But it has long been known that leptin also affects ventilation and the control of breathing.

When transported across the blood-brain barrier, leptin increases the hypercapnic ventilatory response, Babak Mokhlesi, MD, MSc, codirector of the Rush Lung Center and chief of pulmonary, critical care, and sleep medicine at Rush University Medical Center in Chicago, said in an interview.

Research suggests that patients with OHS may have resistance to leptin at the central nervous system level – with leptin not reaching the sites of ventilatory control. This is a “prevailing theory” and could explain why these patients “do not augment their ventilation to maintain homeostasis, normal levels of CO₂,” Dr. Mokhlesi said.

“Why some patients with severe obesity develop CO₂ retention while others do not is not fully understood,” he said, noting that patients with OHS can normalize their CO₂ quickly when instructed to take deep breaths. “What we know is that the centers in the brain responsible for augmenting ventilation when CO₂ goes up are somehow blunted.”

In a study of obese mice led by Vsevolod Y. Polotsky, MD, PhD, of Johns Hopkins University, Baltimore – and highlighted by Dr. Mokhlesi as an example of important, recent research – leptin delivered intranasally alleviated hypoventilation (and upper-airway obstruction), while intraperitoneally administered leptin did not, seemingly overcoming “central leptin deficiency.” (Am J Respir Crit Care Med. 2019;199[6]:773-83).

“This proved that there is some level of resistance in this animal model ... and has potential for therapeutics in the future,” Dr. Mokhlesi said.

Understanding the role of insulin resistance in OSA is another research focus. Some data suggest that insulin resistance, which is more common in obesity, is more prevalent in populations with OSA, Dr. Patil said. Researchers have discussed a bidirectional relationship for years, but it’s likely that insulin resistance is a precursor, he said.

In a mechanistic study published in 2016, Dr. Patil and his coinvestigators found that obese individuals with insulin resistance but without frank diabetes or sleep apnea demonstrated preclinical elevations in pharyngeal collapsibility during sleep. The findings suggest that insulin resistance could play a causal role in OSA pathogenesis by “generating requisite elevations in pharyngeal collapsibility,” they wrote (Eur. Respir J. 2016;47[6]:1718-26).

More recently, Dr. Patil noted in the interview, there is increasing appreciation in academia that the type of fat may be important to predicting OSA. “Visceral fat has a completely different cytokine-secretion profile than subcutaneous fat ... it is the more metabolically active fat that may secondarily impact upper airway function though a neuroinflammatory mechanism,” he said. “That is one of the working hypotheses today.”
 

Asthma

Research has so roundly suggested that metabolic dysfunction contributes to severe, poorly controlled asthma that there’s recent and growing interest in targeting metabolic dysfunction as part of the treatment of obese asthma, said Dr. Dixon, whose own research in obesity and lung disease has focused on asthma.

Data from animal models and some epidemiologic studies have suggested that drugs used to treat type 2 diabetes mellitus, such as glucagon-like peptide receptor-1 (GLPR-1) agonists and metformin, may help control asthma. In one recent study – cited by Dr. Dixon in a 2022 review of obesity and asthma – people with obesity and asthma who were prescribed GLPR-1 agonists for diabetes had fewer asthma exacerbations compared with those who took other medications for diabetes (Semin Respir Crit Care Med. 2022 Feb 17. doi: 10.1055/s-0042-1742384).

There is also research interest in targeting the pro-inflammatory adipokine interleukin 6 (IL-6), since increased circulating levels of IL-6 correlate with asthma severity, and in addressing oxidative stress in asthma through treatment with a mitochondrially targeted antioxidant, she said. Oxidative stress is increased in the airways of people with obesity, and researchers believe it may contribute to the pathophysiology of obese asthma through effects on airway nitric oxide levels.

(Her own research work at the University of Vermont has found associations between poor asthma control and high levels of leptin, and similar associations involving low levels of adiponectin, an anti-inflammatory adipokine that has been shown to downregulate eosinophil recruitment in the airways.)

Weight loss has been shown in mostly small, single-center studies to improve asthma control, but short of weight loss, researchers are also investigating the role of poor dietary quality. Thus far, data suggest that it’s the composition of the diet, and not just its contribution to weight gain, that could be impactful, Dr. Dixon said.

More basic research questions cited by Dr. Dixon include the extent to which adipose tissue inflammation causes inflammation in the lungs. “It’s a little unclear whether all the metabolic dysfunction associated with poor asthma control is causing inflammation in the lungs,” she said, though “we’ve done some work here that shows mediators produced by the adipose tissue could be impacting production of inflammatory mediators by the airway epithelium.”

Overall, she said, “the big questions [in asthma] are, how does adipose tissue affect the airway? Is it through direct effects? Through effects on the immune system? And obesity is affected by diet and the gut microbiome – how can these be [impacting] the airway?”

Obesity “is associated with so many changes – the gut, the immune system, and metabolic dysfunction, in addition to airway mechanics,” she said, “that I no longer think, as I did when I came to this, that it’s just one thing. It’s probably all of these things together.”

In the meantime, questions about potential shared pathways for the development of obesity and asthma remain. “Obesity is a risk factor for developing asthma, but it’s also entirely possible that asthma is a risk factor for developing obesity,” she said. (Some data from pediatric populations, she noted, suggest that nonobese children with asthma are at increased risk of developing obesity.)

Also important, Dr. Dixon said, is “emerging literature in the last 5-10 years” that suggests that people with obesity are more susceptible to the effects of air pollution. Research involving inner-city schoolchildren with asthma, for instance, has shown that those with obesity had worse symptoms with air pollution exposure than did those who were not obese.
 

Pulmonary arterial hypertension

Some research has looked at adipose tissue–produced substances in PAH, but the most well-established association in obesity and PAH involves insulin resistance.

“I don’t think we’re certain as a community that obesity [in general] is the problem – it’s not itself considered a risk factor for PAH,” Anna R. Hemnes, MD, associate professor of medicine at Vanderbilt University Medical Center in Nashville, Tenn., said in an interview. She noted that it’s “hard to dissect obesity” apart.

Researchers are “more confident,” she said, “that insulin resistance – one feature of obesity [in some people] – is associated with worse outcomes in PAH.” Metabolic disease resembling insulin resistance is common in PAH and is believed to contribute to pulmonary vascular disease and right ventricular (RV) failure – the main cause of mortality in PAH – at least in part because of increased oxidative stress.

Dr. Hemnes led a mechanistic phase II clinical trial of metformin in PAH in which the drug was associated with improved RV fractional area change and reduced RV lipid deposition (J Am Heart Assoc. 2020;9[22]:e018349), and she’s now leading a National Institutes of Health–funded multicenter trial looking at the impact of metformin and an exercise intervention on 6-minute walk distance and World Health Organization functional class in PAH.

At the Rush Lung Center, in the meantime, Dr. Mokhlesi is utilizing animal models of OSA and OHS to explore the effect of hypoxia and nighttime hypercapnia on the development of PAH. “I think the jury is still out as to whether obesity itself is a major risk factor, but if so, by what mechanism?” he said. “Is it worsening [sleep-disordered breathing], which then worsens PAH?”
 

COPD

The focus in COPD has traditionally been on underweight, but the relationship between obesity and COPD has increasingly been recognized in the last 10-15 years, said Frits M. E. Franssen, MD, PhD, of CIRO, a research institute in Horn, the Netherlands, that treats COPD and other chronic lung diseases, and of the department of respiratory medicine at Maastricht University.

Researchers like Dr. Franssen are trying, for one, to understand obesity’s impact on COPD pathophysiology and to tease apart the impact of both conditions on disease severity and patient-related outcomes such as exercise capacity and exercise-related symptoms.

When Dr. Franssen’s group compared responses to weight-bearing exercise (6-min. walk test) and weight-supported exercise (cycling) in obese and normal weight COPD patients matched for age, gender, and degree of airflow limitation, the researchers found that walking capacity was significantly reduced while cycling capacity was preserved in the obese group (Respirology. 2016;21[3]:483-8).

Exercise-related symptoms (dyspnea and leg fatigue) were largely comparable between the obese and normal-weight COPD patients in both exercise modalities. However, in other studies, dyspnea ratings during cycling – at any given level of ventilation – have been lower in obese patients, indicating that “additional fat mass may have a beneficial effect on lung functioning [in non–weight-bearing exercise],” he said in an interview.

Dr. Franssen’s group also has assessed body composition in overweight and obese patients with COPD and found that a significant number have low muscle mass. These patients had worse lung function, exercise tolerance, and muscle strength compared to patients with comparable BMI and normal muscle mass (Respir Res. 2021 Mar 25. doi: 10.1186/s12931-021-01689-w).

“We’d always thought that obese patients have normal muscle mass ... but now we know it can be dramatically low,” he said. In assessing obesity and formulating any weight loss plans, “we’re now interested not only in weight but in the distribution of fat mass and fat-free mass ... and in maintaining muscle mass in patients who are [prescribed dietary interventions].”

Paradoxically, in patients with severe COPD, obesity is associated with prolonged survival, while in patients with mild to moderate COPD, obesity is associated with increased mortality risk, he noted.

The impact of adipose tissue and the chronic inflammation and metabolic disturbances that characterize obesity are currently largely unexplored, he said. Researchers have not yet studied what optimal weights may be for patients with COPD. “And we’re interested in the questions, are body weight and body composition the result of the disease, or [are they] determining the type of COPD one will get?” Dr. Franssen said.

Patients with COPD who are obese have “more of the phenotype of chronic bronchitis,” he noted, “while typical emphysema patients are normally underweight.”

The diverse effects of obesity on lung health and disease are increasingly being teased apart, with researchers honing in on the impact of metabolic dysfunction, circulating inflammatory factors produced by adipose tissue, lipid handling, and other factors – in addition to body mass index – that are associated with the obese state.

“The bird’s eye view is that obesity completely changes lung health. It’s something we’ve only recently begun to appreciate,” said Anne E. Dixon, MA, BM, BCh, director of the Vermont Lung Center at the University of Vermont, Burlington, who is focused on the research field of obesity and lung disease.

OSA and OHS

“With sleep apnea we tend to focus on anatomic considerations, but there may be relationships or interactions between obesity and neuromuscular function and neuroventilatory control,” Susheel P. Patil, MD, PhD, director of the sleep medicine program for University Hospitals and assistant professor at Case Western Reserve University, Cleveland, said in an interview.

Some studies suggest, for instance, that TNF-alpha can increase obstructive sleep apnea (OSA) susceptibility and severity through its neuroventilatory modulating properties during sleep. And the potential for additional proinflammatory cytokines produced by adipose tissue to similarly affect upper airway neuroventilatory control is an “intriguing line” of inquiry for researchers in the sleep apnea space, he said.

Leptin is of interest particularly in obesity hypoventilation syndrome (OHS), which is characterized by chronic daytime hypercapnia. Best known as a satiety hormone, leptin is produced by adipose tissue and suppresses appetite at the central nervous system level. But it has long been known that leptin also affects ventilation and the control of breathing.

When transported across the blood-brain barrier, leptin increases the hypercapnic ventilatory response, Babak Mokhlesi, MD, MSc, codirector of the Rush Lung Center and chief of pulmonary, critical care, and sleep medicine at Rush University Medical Center in Chicago, said in an interview.

Research suggests that patients with OHS may have resistance to leptin at the central nervous system level – with leptin not reaching the sites of ventilatory control. This is a “prevailing theory” and could explain why these patients “do not augment their ventilation to maintain homeostasis, normal levels of CO₂,” Dr. Mokhlesi said.

“Why some patients with severe obesity develop CO₂ retention while others do not is not fully understood,” he said, noting that patients with OHS can normalize their CO₂ quickly when instructed to take deep breaths. “What we know is that the centers in the brain responsible for augmenting ventilation when CO₂ goes up are somehow blunted.”

In a study of obese mice led by Vsevolod Y. Polotsky, MD, PhD, of Johns Hopkins University, Baltimore – and highlighted by Dr. Mokhlesi as an example of important, recent research – leptin delivered intranasally alleviated hypoventilation (and upper-airway obstruction), while intraperitoneally administered leptin did not, seemingly overcoming “central leptin deficiency.” (Am J Respir Crit Care Med. 2019;199[6]:773-83).

“This proved that there is some level of resistance in this animal model ... and has potential for therapeutics in the future,” Dr. Mokhlesi said.

Understanding the role of insulin resistance in OSA is another research focus. Some data suggest that insulin resistance, which is more common in obesity, is more prevalent in populations with OSA, Dr. Patil said. Researchers have discussed a bidirectional relationship for years, but it’s likely that insulin resistance is a precursor, he said.

In a mechanistic study published in 2016, Dr. Patil and his coinvestigators found that obese individuals with insulin resistance but without frank diabetes or sleep apnea demonstrated preclinical elevations in pharyngeal collapsibility during sleep. The findings suggest that insulin resistance could play a causal role in OSA pathogenesis by “generating requisite elevations in pharyngeal collapsibility,” they wrote (Eur. Respir J. 2016;47[6]:1718-26).

More recently, Dr. Patil noted in the interview, there is increasing appreciation in academia that the type of fat may be important to predicting OSA. “Visceral fat has a completely different cytokine-secretion profile than subcutaneous fat ... it is the more metabolically active fat that may secondarily impact upper airway function though a neuroinflammatory mechanism,” he said. “That is one of the working hypotheses today.”
 

Asthma

Research has so roundly suggested that metabolic dysfunction contributes to severe, poorly controlled asthma that there’s recent and growing interest in targeting metabolic dysfunction as part of the treatment of obese asthma, said Dr. Dixon, whose own research in obesity and lung disease has focused on asthma.

Data from animal models and some epidemiologic studies have suggested that drugs used to treat type 2 diabetes mellitus, such as glucagon-like peptide receptor-1 (GLPR-1) agonists and metformin, may help control asthma. In one recent study – cited by Dr. Dixon in a 2022 review of obesity and asthma – people with obesity and asthma who were prescribed GLPR-1 agonists for diabetes had fewer asthma exacerbations compared with those who took other medications for diabetes (Semin Respir Crit Care Med. 2022 Feb 17. doi: 10.1055/s-0042-1742384).

There is also research interest in targeting the pro-inflammatory adipokine interleukin 6 (IL-6), since increased circulating levels of IL-6 correlate with asthma severity, and in addressing oxidative stress in asthma through treatment with a mitochondrially targeted antioxidant, she said. Oxidative stress is increased in the airways of people with obesity, and researchers believe it may contribute to the pathophysiology of obese asthma through effects on airway nitric oxide levels.

(Her own research work at the University of Vermont has found associations between poor asthma control and high levels of leptin, and similar associations involving low levels of adiponectin, an anti-inflammatory adipokine that has been shown to downregulate eosinophil recruitment in the airways.)

Weight loss has been shown in mostly small, single-center studies to improve asthma control, but short of weight loss, researchers are also investigating the role of poor dietary quality. Thus far, data suggest that it’s the composition of the diet, and not just its contribution to weight gain, that could be impactful, Dr. Dixon said.

More basic research questions cited by Dr. Dixon include the extent to which adipose tissue inflammation causes inflammation in the lungs. “It’s a little unclear whether all the metabolic dysfunction associated with poor asthma control is causing inflammation in the lungs,” she said, though “we’ve done some work here that shows mediators produced by the adipose tissue could be impacting production of inflammatory mediators by the airway epithelium.”

Overall, she said, “the big questions [in asthma] are, how does adipose tissue affect the airway? Is it through direct effects? Through effects on the immune system? And obesity is affected by diet and the gut microbiome – how can these be [impacting] the airway?”

Obesity “is associated with so many changes – the gut, the immune system, and metabolic dysfunction, in addition to airway mechanics,” she said, “that I no longer think, as I did when I came to this, that it’s just one thing. It’s probably all of these things together.”

In the meantime, questions about potential shared pathways for the development of obesity and asthma remain. “Obesity is a risk factor for developing asthma, but it’s also entirely possible that asthma is a risk factor for developing obesity,” she said. (Some data from pediatric populations, she noted, suggest that nonobese children with asthma are at increased risk of developing obesity.)

Also important, Dr. Dixon said, is “emerging literature in the last 5-10 years” that suggests that people with obesity are more susceptible to the effects of air pollution. Research involving inner-city schoolchildren with asthma, for instance, has shown that those with obesity had worse symptoms with air pollution exposure than did those who were not obese.
 

Pulmonary arterial hypertension

Some research has looked at adipose tissue–produced substances in PAH, but the most well-established association in obesity and PAH involves insulin resistance.

“I don’t think we’re certain as a community that obesity [in general] is the problem – it’s not itself considered a risk factor for PAH,” Anna R. Hemnes, MD, associate professor of medicine at Vanderbilt University Medical Center in Nashville, Tenn., said in an interview. She noted that it’s “hard to dissect obesity” apart.

Researchers are “more confident,” she said, “that insulin resistance – one feature of obesity [in some people] – is associated with worse outcomes in PAH.” Metabolic disease resembling insulin resistance is common in PAH and is believed to contribute to pulmonary vascular disease and right ventricular (RV) failure – the main cause of mortality in PAH – at least in part because of increased oxidative stress.

Dr. Hemnes led a mechanistic phase II clinical trial of metformin in PAH in which the drug was associated with improved RV fractional area change and reduced RV lipid deposition (J Am Heart Assoc. 2020;9[22]:e018349), and she’s now leading a National Institutes of Health–funded multicenter trial looking at the impact of metformin and an exercise intervention on 6-minute walk distance and World Health Organization functional class in PAH.

At the Rush Lung Center, in the meantime, Dr. Mokhlesi is utilizing animal models of OSA and OHS to explore the effect of hypoxia and nighttime hypercapnia on the development of PAH. “I think the jury is still out as to whether obesity itself is a major risk factor, but if so, by what mechanism?” he said. “Is it worsening [sleep-disordered breathing], which then worsens PAH?”
 

COPD

The focus in COPD has traditionally been on underweight, but the relationship between obesity and COPD has increasingly been recognized in the last 10-15 years, said Frits M. E. Franssen, MD, PhD, of CIRO, a research institute in Horn, the Netherlands, that treats COPD and other chronic lung diseases, and of the department of respiratory medicine at Maastricht University.

Researchers like Dr. Franssen are trying, for one, to understand obesity’s impact on COPD pathophysiology and to tease apart the impact of both conditions on disease severity and patient-related outcomes such as exercise capacity and exercise-related symptoms.

When Dr. Franssen’s group compared responses to weight-bearing exercise (6-min. walk test) and weight-supported exercise (cycling) in obese and normal weight COPD patients matched for age, gender, and degree of airflow limitation, the researchers found that walking capacity was significantly reduced while cycling capacity was preserved in the obese group (Respirology. 2016;21[3]:483-8).

Exercise-related symptoms (dyspnea and leg fatigue) were largely comparable between the obese and normal-weight COPD patients in both exercise modalities. However, in other studies, dyspnea ratings during cycling – at any given level of ventilation – have been lower in obese patients, indicating that “additional fat mass may have a beneficial effect on lung functioning [in non–weight-bearing exercise],” he said in an interview.

Dr. Franssen’s group also has assessed body composition in overweight and obese patients with COPD and found that a significant number have low muscle mass. These patients had worse lung function, exercise tolerance, and muscle strength compared to patients with comparable BMI and normal muscle mass (Respir Res. 2021 Mar 25. doi: 10.1186/s12931-021-01689-w).

“We’d always thought that obese patients have normal muscle mass ... but now we know it can be dramatically low,” he said. In assessing obesity and formulating any weight loss plans, “we’re now interested not only in weight but in the distribution of fat mass and fat-free mass ... and in maintaining muscle mass in patients who are [prescribed dietary interventions].”

Paradoxically, in patients with severe COPD, obesity is associated with prolonged survival, while in patients with mild to moderate COPD, obesity is associated with increased mortality risk, he noted.

The impact of adipose tissue and the chronic inflammation and metabolic disturbances that characterize obesity are currently largely unexplored, he said. Researchers have not yet studied what optimal weights may be for patients with COPD. “And we’re interested in the questions, are body weight and body composition the result of the disease, or [are they] determining the type of COPD one will get?” Dr. Franssen said.

Patients with COPD who are obese have “more of the phenotype of chronic bronchitis,” he noted, “while typical emphysema patients are normally underweight.”

The diverse effects of obesity on lung health and disease are increasingly being teased apart, with researchers honing in on the impact of metabolic dysfunction, circulating inflammatory factors produced by adipose tissue, lipid handling, and other factors – in addition to body mass index – that are associated with the obese state.

“The bird’s eye view is that obesity completely changes lung health. It’s something we’ve only recently begun to appreciate,” said Anne E. Dixon, MA, BM, BCh, director of the Vermont Lung Center at the University of Vermont, Burlington, who is focused on the research field of obesity and lung disease.

OSA and OHS

“With sleep apnea we tend to focus on anatomic considerations, but there may be relationships or interactions between obesity and neuromuscular function and neuroventilatory control,” Susheel P. Patil, MD, PhD, director of the sleep medicine program for University Hospitals and assistant professor at Case Western Reserve University, Cleveland, said in an interview.

Some studies suggest, for instance, that TNF-alpha can increase obstructive sleep apnea (OSA) susceptibility and severity through its neuroventilatory modulating properties during sleep. And the potential for additional proinflammatory cytokines produced by adipose tissue to similarly affect upper airway neuroventilatory control is an “intriguing line” of inquiry for researchers in the sleep apnea space, he said.

Leptin is of interest particularly in obesity hypoventilation syndrome (OHS), which is characterized by chronic daytime hypercapnia. Best known as a satiety hormone, leptin is produced by adipose tissue and suppresses appetite at the central nervous system level. But it has long been known that leptin also affects ventilation and the control of breathing.

When transported across the blood-brain barrier, leptin increases the hypercapnic ventilatory response, Babak Mokhlesi, MD, MSc, codirector of the Rush Lung Center and chief of pulmonary, critical care, and sleep medicine at Rush University Medical Center in Chicago, said in an interview.

Research suggests that patients with OHS may have resistance to leptin at the central nervous system level – with leptin not reaching the sites of ventilatory control. This is a “prevailing theory” and could explain why these patients “do not augment their ventilation to maintain homeostasis, normal levels of CO₂,” Dr. Mokhlesi said.

“Why some patients with severe obesity develop CO₂ retention while others do not is not fully understood,” he said, noting that patients with OHS can normalize their CO₂ quickly when instructed to take deep breaths. “What we know is that the centers in the brain responsible for augmenting ventilation when CO₂ goes up are somehow blunted.”

In a study of obese mice led by Vsevolod Y. Polotsky, MD, PhD, of Johns Hopkins University, Baltimore – and highlighted by Dr. Mokhlesi as an example of important, recent research – leptin delivered intranasally alleviated hypoventilation (and upper-airway obstruction), while intraperitoneally administered leptin did not, seemingly overcoming “central leptin deficiency.” (Am J Respir Crit Care Med. 2019;199[6]:773-83).

“This proved that there is some level of resistance in this animal model ... and has potential for therapeutics in the future,” Dr. Mokhlesi said.

Understanding the role of insulin resistance in OSA is another research focus. Some data suggest that insulin resistance, which is more common in obesity, is more prevalent in populations with OSA, Dr. Patil said. Researchers have discussed a bidirectional relationship for years, but it’s likely that insulin resistance is a precursor, he said.

In a mechanistic study published in 2016, Dr. Patil and his coinvestigators found that obese individuals with insulin resistance but without frank diabetes or sleep apnea demonstrated preclinical elevations in pharyngeal collapsibility during sleep. The findings suggest that insulin resistance could play a causal role in OSA pathogenesis by “generating requisite elevations in pharyngeal collapsibility,” they wrote (Eur. Respir J. 2016;47[6]:1718-26).

More recently, Dr. Patil noted in the interview, there is increasing appreciation in academia that the type of fat may be important to predicting OSA. “Visceral fat has a completely different cytokine-secretion profile than subcutaneous fat ... it is the more metabolically active fat that may secondarily impact upper airway function though a neuroinflammatory mechanism,” he said. “That is one of the working hypotheses today.”
 

Asthma

Research has so roundly suggested that metabolic dysfunction contributes to severe, poorly controlled asthma that there’s recent and growing interest in targeting metabolic dysfunction as part of the treatment of obese asthma, said Dr. Dixon, whose own research in obesity and lung disease has focused on asthma.

Data from animal models and some epidemiologic studies have suggested that drugs used to treat type 2 diabetes mellitus, such as glucagon-like peptide receptor-1 (GLPR-1) agonists and metformin, may help control asthma. In one recent study – cited by Dr. Dixon in a 2022 review of obesity and asthma – people with obesity and asthma who were prescribed GLPR-1 agonists for diabetes had fewer asthma exacerbations compared with those who took other medications for diabetes (Semin Respir Crit Care Med. 2022 Feb 17. doi: 10.1055/s-0042-1742384).

There is also research interest in targeting the pro-inflammatory adipokine interleukin 6 (IL-6), since increased circulating levels of IL-6 correlate with asthma severity, and in addressing oxidative stress in asthma through treatment with a mitochondrially targeted antioxidant, she said. Oxidative stress is increased in the airways of people with obesity, and researchers believe it may contribute to the pathophysiology of obese asthma through effects on airway nitric oxide levels.

(Her own research work at the University of Vermont has found associations between poor asthma control and high levels of leptin, and similar associations involving low levels of adiponectin, an anti-inflammatory adipokine that has been shown to downregulate eosinophil recruitment in the airways.)

Weight loss has been shown in mostly small, single-center studies to improve asthma control, but short of weight loss, researchers are also investigating the role of poor dietary quality. Thus far, data suggest that it’s the composition of the diet, and not just its contribution to weight gain, that could be impactful, Dr. Dixon said.

More basic research questions cited by Dr. Dixon include the extent to which adipose tissue inflammation causes inflammation in the lungs. “It’s a little unclear whether all the metabolic dysfunction associated with poor asthma control is causing inflammation in the lungs,” she said, though “we’ve done some work here that shows mediators produced by the adipose tissue could be impacting production of inflammatory mediators by the airway epithelium.”

Overall, she said, “the big questions [in asthma] are, how does adipose tissue affect the airway? Is it through direct effects? Through effects on the immune system? And obesity is affected by diet and the gut microbiome – how can these be [impacting] the airway?”

Obesity “is associated with so many changes – the gut, the immune system, and metabolic dysfunction, in addition to airway mechanics,” she said, “that I no longer think, as I did when I came to this, that it’s just one thing. It’s probably all of these things together.”

In the meantime, questions about potential shared pathways for the development of obesity and asthma remain. “Obesity is a risk factor for developing asthma, but it’s also entirely possible that asthma is a risk factor for developing obesity,” she said. (Some data from pediatric populations, she noted, suggest that nonobese children with asthma are at increased risk of developing obesity.)

Also important, Dr. Dixon said, is “emerging literature in the last 5-10 years” that suggests that people with obesity are more susceptible to the effects of air pollution. Research involving inner-city schoolchildren with asthma, for instance, has shown that those with obesity had worse symptoms with air pollution exposure than did those who were not obese.
 

Pulmonary arterial hypertension

Some research has looked at adipose tissue–produced substances in PAH, but the most well-established association in obesity and PAH involves insulin resistance.

“I don’t think we’re certain as a community that obesity [in general] is the problem – it’s not itself considered a risk factor for PAH,” Anna R. Hemnes, MD, associate professor of medicine at Vanderbilt University Medical Center in Nashville, Tenn., said in an interview. She noted that it’s “hard to dissect obesity” apart.

Researchers are “more confident,” she said, “that insulin resistance – one feature of obesity [in some people] – is associated with worse outcomes in PAH.” Metabolic disease resembling insulin resistance is common in PAH and is believed to contribute to pulmonary vascular disease and right ventricular (RV) failure – the main cause of mortality in PAH – at least in part because of increased oxidative stress.

Dr. Hemnes led a mechanistic phase II clinical trial of metformin in PAH in which the drug was associated with improved RV fractional area change and reduced RV lipid deposition (J Am Heart Assoc. 2020;9[22]:e018349), and she’s now leading a National Institutes of Health–funded multicenter trial looking at the impact of metformin and an exercise intervention on 6-minute walk distance and World Health Organization functional class in PAH.

At the Rush Lung Center, in the meantime, Dr. Mokhlesi is utilizing animal models of OSA and OHS to explore the effect of hypoxia and nighttime hypercapnia on the development of PAH. “I think the jury is still out as to whether obesity itself is a major risk factor, but if so, by what mechanism?” he said. “Is it worsening [sleep-disordered breathing], which then worsens PAH?”
 

COPD

The focus in COPD has traditionally been on underweight, but the relationship between obesity and COPD has increasingly been recognized in the last 10-15 years, said Frits M. E. Franssen, MD, PhD, of CIRO, a research institute in Horn, the Netherlands, that treats COPD and other chronic lung diseases, and of the department of respiratory medicine at Maastricht University.

Researchers like Dr. Franssen are trying, for one, to understand obesity’s impact on COPD pathophysiology and to tease apart the impact of both conditions on disease severity and patient-related outcomes such as exercise capacity and exercise-related symptoms.

When Dr. Franssen’s group compared responses to weight-bearing exercise (6-min. walk test) and weight-supported exercise (cycling) in obese and normal weight COPD patients matched for age, gender, and degree of airflow limitation, the researchers found that walking capacity was significantly reduced while cycling capacity was preserved in the obese group (Respirology. 2016;21[3]:483-8).

Exercise-related symptoms (dyspnea and leg fatigue) were largely comparable between the obese and normal-weight COPD patients in both exercise modalities. However, in other studies, dyspnea ratings during cycling – at any given level of ventilation – have been lower in obese patients, indicating that “additional fat mass may have a beneficial effect on lung functioning [in non–weight-bearing exercise],” he said in an interview.

Dr. Franssen’s group also has assessed body composition in overweight and obese patients with COPD and found that a significant number have low muscle mass. These patients had worse lung function, exercise tolerance, and muscle strength compared to patients with comparable BMI and normal muscle mass (Respir Res. 2021 Mar 25. doi: 10.1186/s12931-021-01689-w).

“We’d always thought that obese patients have normal muscle mass ... but now we know it can be dramatically low,” he said. In assessing obesity and formulating any weight loss plans, “we’re now interested not only in weight but in the distribution of fat mass and fat-free mass ... and in maintaining muscle mass in patients who are [prescribed dietary interventions].”

Paradoxically, in patients with severe COPD, obesity is associated with prolonged survival, while in patients with mild to moderate COPD, obesity is associated with increased mortality risk, he noted.

The impact of adipose tissue and the chronic inflammation and metabolic disturbances that characterize obesity are currently largely unexplored, he said. Researchers have not yet studied what optimal weights may be for patients with COPD. “And we’re interested in the questions, are body weight and body composition the result of the disease, or [are they] determining the type of COPD one will get?” Dr. Franssen said.

Patients with COPD who are obese have “more of the phenotype of chronic bronchitis,” he noted, “while typical emphysema patients are normally underweight.”

More teenagers in the United States reported cannabis use with vaping in 2019, compared with 2017, while cannabis use without vaping declined, based on annual survey data from more than 50,000 teens.

“With vaping prevalence rising so quickly among teens, getting a clearer picture of how cannabis use is shifting helps inform prevention and cessation efforts,” corresponding author Noah T. Kreski, MPH, of Columbia University, New York, said in an interview.

“In just 2 years, the most common cannabis use pattern changed from ‘occasional use without vaping’ to ‘frequent use with vaping,’ said Mx. Kreski, who uses the honorific Mx. and the pronouns they/them. “Knowing that, as well as the high overlap of cannabis vaping with nicotine use and binge drinking, adds to the urgency of reducing adolescent vaping.”

To quantify the trends in cannabis vaping, the researchers reviewed data from Monitoring the Future, an annual survey of high school students across the United States. The study population included 51,052 individuals; approximately 49% were male and 49% were non-Hispanic White. The researchers examined frequency of cannabis use, trends across demographic groups, and concurrent use of cannabis and other substances such as alcohol and tobacco. The findings were published in the journal Addiction.

Frequent cannabis use was defined as six or more times in the past 30 days; occasional use was defined as one to five times in the past 30 days.

Frequent cannabis use with vaping increased from 2.1% in 2017 to 5.4% in 2019. Occasional cannabis use with vaping also increased, though less dramatically, from less than 2% in 2017 to approximately 3.5% in 2019.

By contrast, both frequent and occasional cannabis use without vaping declined from 2017 to 2019 (from 3.8% to 2.1% and from 6.9% to 4.4%, respectively).

Overall, the prevalence of any level of cannabis use increased from 13.9% in 2017 to 15.4% in 2019. Both males and females showed a similar increase in reported frequent cannabis use with vaping of approximately 3%.

The results document that vaping cannabis has become more common than smoking alone among U.S. teens across almost all demographic groups, and across sex, race, urbanicity, and level of parent education; however, the increased was especially marked among Hispanic/Latinx teens and those of lower socioeconomic status, the researchers wrote.

The researchers also examined the associations between cannabis use with and without vaping and concurrent nicotine and alcohol use. Overall, the strongest association was between smoking or vaping nicotine and vaping cannabis; teens who smoked or vaped nicotine were 42 times more likely than nonnicotine users to report vaping cannabis in the past 30 days (adjusted odds ratio, 42.28). In addition, more occasions of binge drinking were more strongly associated with cannabis use with vaping (up to 10 times more likely), compared with cannabis use without vaping, (aORs, 4.48-10.09).

The study findings were limited by several factors, including the lack of questions on tetrahydrocannabinol (THC) or cannabidiol content of the cannabis products used, although evidence suggests that the potency of cannabis products in the United States is increasing, the researchers noted. Other limitations included the cross-sectional design, which prevents making associations about causality, and lack of data on the quantity of cannabis used; only data on frequency of use were recorded.

However, the results reflect a rise in cannabis use with vaping among teens in the United States, along with an increased risk of tobacco use, e-cigarette use, and binge drinking, the researchers said.

As cannabis legalization expands across the United States, policies are needed to deter use among adolescents, the researchers wrote. “These policies should be crafted to reduce an emphasis on criminalization in preference for public health promotion given the history of unequal application of punitive consequences of drug use for racialized minorities in the United States. As products, delivery systems, potency, and marketing proliferate within a for-profit industry, increased attention to youth trends, including investment in sustained and evidence-based prevention and intervention, is increasingly necessary.”

The take-home message for clinicians is to ask whether your patients are vaping, because the prevalence is not only up, but fairly universal, Mx. Kreski said. “Have a discussion that covers a broad range of substance use topics and informs teens of the potential risks of vaping, while avoiding stigma.”

The message for parents is “to talk to your kids about the risks of vaping,” said Mx. Kreski. “Prioritize open communication rather than punishment, and work together with your teens to prevent or reduce vaping.” The message for teens: “Understand that vaping has risks. You should feel empowered to talk to your parents or doctor about those risks. While it may seem like everyone’s vaping, the majority don’t. Keeping communication open between parents/caregivers, teens, and health care providers is one of the best ways to address these trends in vaping.”
 

Beware more powerful cannabis products

“While drug use in general is declining in adolescents, marijuana use remains very common,” Kelly A. Curran, MD, of the University of Oklahoma Health Sciences Center, Oklahoma City, said in an interview.

“There is growing evidence that marijuana is now the first drug used by adolescents – replacing alcohol and nicotine – and frequent use can lead to substance abuse,” said Dr. Curran, who specializes in adolescent medicine but was involved in the study. “Cannabis use patterns have evolved over time. As I frequently tell my patients and their families, new strains and hybrids of marijuana have higher potencies of THC. Many adolescents are eschewing smoking and in its place using marijuana concentrates (wax, oil, shatter) via vape, dab pen, or rig. Use of these methods puts adolescents at high risk of social and health complications such as [e-cigarette or vaping use-associated lung injury], cannabis hyperemesis syndrome, and psychosis – and understanding these patterns and associated drug use helps health care professionals and parents keep adolescents safe.”

The take-home message for clinicians is that marijuana use via vaping continues to rise and to become more common than “traditional” marijuana smoking, Dr. Curran said. “This increase is across genders, in nearly all race/ethnicities (especially in Latinx youth), and in youth from lower socioeconomic status.” Vaping marijuana is associated with other substance abuse, so health care professionals should include questions about different forms of marijuana use, such as vape, dab pen, or rig, when working with patients, and counsel patients and families about the risks associated with use of any of these products.

The study was supported by the National Center for Injury Prevention and Control and by the National Institute on Drug Abuse. The researchers had no financial conflicts to disclose. Dr. Curran had no financial conflicts to disclose and serves on the editorial advisory board of Pediatric News.
 

More teenagers in the United States reported cannabis use with vaping in 2019, compared with 2017, while cannabis use without vaping declined, based on annual survey data from more than 50,000 teens.

“With vaping prevalence rising so quickly among teens, getting a clearer picture of how cannabis use is shifting helps inform prevention and cessation efforts,” corresponding author Noah T. Kreski, MPH, of Columbia University, New York, said in an interview.

“In just 2 years, the most common cannabis use pattern changed from ‘occasional use without vaping’ to ‘frequent use with vaping,’ said Mx. Kreski, who uses the honorific Mx. and the pronouns they/them. “Knowing that, as well as the high overlap of cannabis vaping with nicotine use and binge drinking, adds to the urgency of reducing adolescent vaping.”

To quantify the trends in cannabis vaping, the researchers reviewed data from Monitoring the Future, an annual survey of high school students across the United States. The study population included 51,052 individuals; approximately 49% were male and 49% were non-Hispanic White. The researchers examined frequency of cannabis use, trends across demographic groups, and concurrent use of cannabis and other substances such as alcohol and tobacco. The findings were published in the journal Addiction.

Frequent cannabis use was defined as six or more times in the past 30 days; occasional use was defined as one to five times in the past 30 days.

Frequent cannabis use with vaping increased from 2.1% in 2017 to 5.4% in 2019. Occasional cannabis use with vaping also increased, though less dramatically, from less than 2% in 2017 to approximately 3.5% in 2019.

By contrast, both frequent and occasional cannabis use without vaping declined from 2017 to 2019 (from 3.8% to 2.1% and from 6.9% to 4.4%, respectively).

Overall, the prevalence of any level of cannabis use increased from 13.9% in 2017 to 15.4% in 2019. Both males and females showed a similar increase in reported frequent cannabis use with vaping of approximately 3%.

The results document that vaping cannabis has become more common than smoking alone among U.S. teens across almost all demographic groups, and across sex, race, urbanicity, and level of parent education; however, the increased was especially marked among Hispanic/Latinx teens and those of lower socioeconomic status, the researchers wrote.

The researchers also examined the associations between cannabis use with and without vaping and concurrent nicotine and alcohol use. Overall, the strongest association was between smoking or vaping nicotine and vaping cannabis; teens who smoked or vaped nicotine were 42 times more likely than nonnicotine users to report vaping cannabis in the past 30 days (adjusted odds ratio, 42.28). In addition, more occasions of binge drinking were more strongly associated with cannabis use with vaping (up to 10 times more likely), compared with cannabis use without vaping, (aORs, 4.48-10.09).

The study findings were limited by several factors, including the lack of questions on tetrahydrocannabinol (THC) or cannabidiol content of the cannabis products used, although evidence suggests that the potency of cannabis products in the United States is increasing, the researchers noted. Other limitations included the cross-sectional design, which prevents making associations about causality, and lack of data on the quantity of cannabis used; only data on frequency of use were recorded.

However, the results reflect a rise in cannabis use with vaping among teens in the United States, along with an increased risk of tobacco use, e-cigarette use, and binge drinking, the researchers said.

As cannabis legalization expands across the United States, policies are needed to deter use among adolescents, the researchers wrote. “These policies should be crafted to reduce an emphasis on criminalization in preference for public health promotion given the history of unequal application of punitive consequences of drug use for racialized minorities in the United States. As products, delivery systems, potency, and marketing proliferate within a for-profit industry, increased attention to youth trends, including investment in sustained and evidence-based prevention and intervention, is increasingly necessary.”

The take-home message for clinicians is to ask whether your patients are vaping, because the prevalence is not only up, but fairly universal, Mx. Kreski said. “Have a discussion that covers a broad range of substance use topics and informs teens of the potential risks of vaping, while avoiding stigma.”

The message for parents is “to talk to your kids about the risks of vaping,” said Mx. Kreski. “Prioritize open communication rather than punishment, and work together with your teens to prevent or reduce vaping.” The message for teens: “Understand that vaping has risks. You should feel empowered to talk to your parents or doctor about those risks. While it may seem like everyone’s vaping, the majority don’t. Keeping communication open between parents/caregivers, teens, and health care providers is one of the best ways to address these trends in vaping.”
 

Beware more powerful cannabis products

“While drug use in general is declining in adolescents, marijuana use remains very common,” Kelly A. Curran, MD, of the University of Oklahoma Health Sciences Center, Oklahoma City, said in an interview.

“There is growing evidence that marijuana is now the first drug used by adolescents – replacing alcohol and nicotine – and frequent use can lead to substance abuse,” said Dr. Curran, who specializes in adolescent medicine but was involved in the study. “Cannabis use patterns have evolved over time. As I frequently tell my patients and their families, new strains and hybrids of marijuana have higher potencies of THC. Many adolescents are eschewing smoking and in its place using marijuana concentrates (wax, oil, shatter) via vape, dab pen, or rig. Use of these methods puts adolescents at high risk of social and health complications such as [e-cigarette or vaping use-associated lung injury], cannabis hyperemesis syndrome, and psychosis – and understanding these patterns and associated drug use helps health care professionals and parents keep adolescents safe.”

The take-home message for clinicians is that marijuana use via vaping continues to rise and to become more common than “traditional” marijuana smoking, Dr. Curran said. “This increase is across genders, in nearly all race/ethnicities (especially in Latinx youth), and in youth from lower socioeconomic status.” Vaping marijuana is associated with other substance abuse, so health care professionals should include questions about different forms of marijuana use, such as vape, dab pen, or rig, when working with patients, and counsel patients and families about the risks associated with use of any of these products.

The study was supported by the National Center for Injury Prevention and Control and by the National Institute on Drug Abuse. The researchers had no financial conflicts to disclose. Dr. Curran had no financial conflicts to disclose and serves on the editorial advisory board of Pediatric News.
 

More teenagers in the United States reported cannabis use with vaping in 2019, compared with 2017, while cannabis use without vaping declined, based on annual survey data from more than 50,000 teens.

“With vaping prevalence rising so quickly among teens, getting a clearer picture of how cannabis use is shifting helps inform prevention and cessation efforts,” corresponding author Noah T. Kreski, MPH, of Columbia University, New York, said in an interview.

“In just 2 years, the most common cannabis use pattern changed from ‘occasional use without vaping’ to ‘frequent use with vaping,’ said Mx. Kreski, who uses the honorific Mx. and the pronouns they/them. “Knowing that, as well as the high overlap of cannabis vaping with nicotine use and binge drinking, adds to the urgency of reducing adolescent vaping.”

To quantify the trends in cannabis vaping, the researchers reviewed data from Monitoring the Future, an annual survey of high school students across the United States. The study population included 51,052 individuals; approximately 49% were male and 49% were non-Hispanic White. The researchers examined frequency of cannabis use, trends across demographic groups, and concurrent use of cannabis and other substances such as alcohol and tobacco. The findings were published in the journal Addiction.

Frequent cannabis use was defined as six or more times in the past 30 days; occasional use was defined as one to five times in the past 30 days.

Frequent cannabis use with vaping increased from 2.1% in 2017 to 5.4% in 2019. Occasional cannabis use with vaping also increased, though less dramatically, from less than 2% in 2017 to approximately 3.5% in 2019.

By contrast, both frequent and occasional cannabis use without vaping declined from 2017 to 2019 (from 3.8% to 2.1% and from 6.9% to 4.4%, respectively).

Overall, the prevalence of any level of cannabis use increased from 13.9% in 2017 to 15.4% in 2019. Both males and females showed a similar increase in reported frequent cannabis use with vaping of approximately 3%.

The results document that vaping cannabis has become more common than smoking alone among U.S. teens across almost all demographic groups, and across sex, race, urbanicity, and level of parent education; however, the increased was especially marked among Hispanic/Latinx teens and those of lower socioeconomic status, the researchers wrote.

The researchers also examined the associations between cannabis use with and without vaping and concurrent nicotine and alcohol use. Overall, the strongest association was between smoking or vaping nicotine and vaping cannabis; teens who smoked or vaped nicotine were 42 times more likely than nonnicotine users to report vaping cannabis in the past 30 days (adjusted odds ratio, 42.28). In addition, more occasions of binge drinking were more strongly associated with cannabis use with vaping (up to 10 times more likely), compared with cannabis use without vaping, (aORs, 4.48-10.09).

The study findings were limited by several factors, including the lack of questions on tetrahydrocannabinol (THC) or cannabidiol content of the cannabis products used, although evidence suggests that the potency of cannabis products in the United States is increasing, the researchers noted. Other limitations included the cross-sectional design, which prevents making associations about causality, and lack of data on the quantity of cannabis used; only data on frequency of use were recorded.

However, the results reflect a rise in cannabis use with vaping among teens in the United States, along with an increased risk of tobacco use, e-cigarette use, and binge drinking, the researchers said.

As cannabis legalization expands across the United States, policies are needed to deter use among adolescents, the researchers wrote. “These policies should be crafted to reduce an emphasis on criminalization in preference for public health promotion given the history of unequal application of punitive consequences of drug use for racialized minorities in the United States. As products, delivery systems, potency, and marketing proliferate within a for-profit industry, increased attention to youth trends, including investment in sustained and evidence-based prevention and intervention, is increasingly necessary.”

The take-home message for clinicians is to ask whether your patients are vaping, because the prevalence is not only up, but fairly universal, Mx. Kreski said. “Have a discussion that covers a broad range of substance use topics and informs teens of the potential risks of vaping, while avoiding stigma.”

The message for parents is “to talk to your kids about the risks of vaping,” said Mx. Kreski. “Prioritize open communication rather than punishment, and work together with your teens to prevent or reduce vaping.” The message for teens: “Understand that vaping has risks. You should feel empowered to talk to your parents or doctor about those risks. While it may seem like everyone’s vaping, the majority don’t. Keeping communication open between parents/caregivers, teens, and health care providers is one of the best ways to address these trends in vaping.”
 

Beware more powerful cannabis products

“While drug use in general is declining in adolescents, marijuana use remains very common,” Kelly A. Curran, MD, of the University of Oklahoma Health Sciences Center, Oklahoma City, said in an interview.

“There is growing evidence that marijuana is now the first drug used by adolescents – replacing alcohol and nicotine – and frequent use can lead to substance abuse,” said Dr. Curran, who specializes in adolescent medicine but was involved in the study. “Cannabis use patterns have evolved over time. As I frequently tell my patients and their families, new strains and hybrids of marijuana have higher potencies of THC. Many adolescents are eschewing smoking and in its place using marijuana concentrates (wax, oil, shatter) via vape, dab pen, or rig. Use of these methods puts adolescents at high risk of social and health complications such as [e-cigarette or vaping use-associated lung injury], cannabis hyperemesis syndrome, and psychosis – and understanding these patterns and associated drug use helps health care professionals and parents keep adolescents safe.”

The take-home message for clinicians is that marijuana use via vaping continues to rise and to become more common than “traditional” marijuana smoking, Dr. Curran said. “This increase is across genders, in nearly all race/ethnicities (especially in Latinx youth), and in youth from lower socioeconomic status.” Vaping marijuana is associated with other substance abuse, so health care professionals should include questions about different forms of marijuana use, such as vape, dab pen, or rig, when working with patients, and counsel patients and families about the risks associated with use of any of these products.

The study was supported by the National Center for Injury Prevention and Control and by the National Institute on Drug Abuse. The researchers had no financial conflicts to disclose. Dr. Curran had no financial conflicts to disclose and serves on the editorial advisory board of Pediatric News.
 

SAN FRANCISCO – It may be time to move beyond relying largely on spirometry to distinguish between healthy and abnormal lung function in diverse populations.

That conclusion comes from investigators who looked at patients with ostensibly normal spirometry values in a large population-based study and found that using standard equations to adjust for racial differences in lung-function measures appeared to miss emphysema in a significant proportion of Black patients.

“Our traditional measures of lung health based on spirometry may be under-recognizing impaired respiratory health in Black adults and particularly Black men,” said lead author Gabrielle Liu, MD, a fellow in the division of pulmonary and critical care medicine at the Northwestern University Feinberg School of Medicine, Chicago.

“CT imaging may be useful in the evaluation of those with suspected impaired respiratory health and normal spirometry,” she said in an oral abstract session at the American Thoracic Society International Conference 2022.

Dr. Liu and colleagues studied the association between self-identified race and visually identified emphysema among 2,674 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study. The patients had CT scans at a mean age of 50 and spirometry at a mean age of 55.
 

Racial differences

The investigators found that among men with forced expiratory volume in 1 second (FEV1) ranging from 100% to 120% of predicted according to race-adjusted formulas, 14.6% of Black men had emphysema, compared with only 1.7% of White men (P < .001). Respective emphysema rates in Black women and White women were 3.8% and 1.9%; this difference was not statistically significant.

Among patients with FEV1 80% to 99% of predicted according to race-specific measures, 15.5% of Black men had emphysema, compared with 4% of White men (P < .001). Respective rates of emphysema were 6.9% for Black women versus 3.2% for White women (P = .025).

When the investigators applied race-neutral spirometry reference equations to the same population, they found that it attenuated but did not completely eliminate the racial disparity in emphysema prevalence among patients with FEV1, ranging from 80% to 120% of predicted.
 

Relic of the past

The results suggest that race-based adjustments of spirometry measures are a relic of less enlightened times, said Adam Gaffney, MD, MPH, assistant professor of medicine at Harvard Medical School, Boston, and a pulmonologist and critical care physician at Cambridge Health Alliance, Massachusetts.

“If the average lower lung function of Black people is being driven by adversity, structural racism, and deprivation, that means that race-specific equations are normalizing that adversity,” he said in an interview.

“In my opinion, it is time to move beyond race-based equations in clinical pulmonary medicine, particularly in the context of patients with established lung disease in whom use of race-based equations might actually lead to undertreatment,” said Dr. Gaffney, who was not involved in the study.

Dr. Liu agreed that it’s time to move to race-neutral measures and that the whole concept of race-based differences is flawed.

“The long-standing structural inequities in health likely made the reference populations have lower lung function than among Whites,” she told this news organization.

Dr. Liu said that evaluation of lung function should not rely on spirometry alone, but should also include – when appropriate – CT scans, as well as improved understanding of how symptoms may be predictive for poor outcomes.

The study was supported by grants from the National Institutes of Health. Dr. Liu and Dr. Gaffney have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

SAN FRANCISCO – It may be time to move beyond relying largely on spirometry to distinguish between healthy and abnormal lung function in diverse populations.

That conclusion comes from investigators who looked at patients with ostensibly normal spirometry values in a large population-based study and found that using standard equations to adjust for racial differences in lung-function measures appeared to miss emphysema in a significant proportion of Black patients.

“Our traditional measures of lung health based on spirometry may be under-recognizing impaired respiratory health in Black adults and particularly Black men,” said lead author Gabrielle Liu, MD, a fellow in the division of pulmonary and critical care medicine at the Northwestern University Feinberg School of Medicine, Chicago.

“CT imaging may be useful in the evaluation of those with suspected impaired respiratory health and normal spirometry,” she said in an oral abstract session at the American Thoracic Society International Conference 2022.

Dr. Liu and colleagues studied the association between self-identified race and visually identified emphysema among 2,674 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study. The patients had CT scans at a mean age of 50 and spirometry at a mean age of 55.
 

Racial differences

The investigators found that among men with forced expiratory volume in 1 second (FEV1) ranging from 100% to 120% of predicted according to race-adjusted formulas, 14.6% of Black men had emphysema, compared with only 1.7% of White men (P < .001). Respective emphysema rates in Black women and White women were 3.8% and 1.9%; this difference was not statistically significant.

Among patients with FEV1 80% to 99% of predicted according to race-specific measures, 15.5% of Black men had emphysema, compared with 4% of White men (P < .001). Respective rates of emphysema were 6.9% for Black women versus 3.2% for White women (P = .025).

When the investigators applied race-neutral spirometry reference equations to the same population, they found that it attenuated but did not completely eliminate the racial disparity in emphysema prevalence among patients with FEV1, ranging from 80% to 120% of predicted.
 

Relic of the past

The results suggest that race-based adjustments of spirometry measures are a relic of less enlightened times, said Adam Gaffney, MD, MPH, assistant professor of medicine at Harvard Medical School, Boston, and a pulmonologist and critical care physician at Cambridge Health Alliance, Massachusetts.

“If the average lower lung function of Black people is being driven by adversity, structural racism, and deprivation, that means that race-specific equations are normalizing that adversity,” he said in an interview.

“In my opinion, it is time to move beyond race-based equations in clinical pulmonary medicine, particularly in the context of patients with established lung disease in whom use of race-based equations might actually lead to undertreatment,” said Dr. Gaffney, who was not involved in the study.

Dr. Liu agreed that it’s time to move to race-neutral measures and that the whole concept of race-based differences is flawed.

“The long-standing structural inequities in health likely made the reference populations have lower lung function than among Whites,” she told this news organization.

Dr. Liu said that evaluation of lung function should not rely on spirometry alone, but should also include – when appropriate – CT scans, as well as improved understanding of how symptoms may be predictive for poor outcomes.

The study was supported by grants from the National Institutes of Health. Dr. Liu and Dr. Gaffney have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

SAN FRANCISCO – It may be time to move beyond relying largely on spirometry to distinguish between healthy and abnormal lung function in diverse populations.

That conclusion comes from investigators who looked at patients with ostensibly normal spirometry values in a large population-based study and found that using standard equations to adjust for racial differences in lung-function measures appeared to miss emphysema in a significant proportion of Black patients.

“Our traditional measures of lung health based on spirometry may be under-recognizing impaired respiratory health in Black adults and particularly Black men,” said lead author Gabrielle Liu, MD, a fellow in the division of pulmonary and critical care medicine at the Northwestern University Feinberg School of Medicine, Chicago.

“CT imaging may be useful in the evaluation of those with suspected impaired respiratory health and normal spirometry,” she said in an oral abstract session at the American Thoracic Society International Conference 2022.

Dr. Liu and colleagues studied the association between self-identified race and visually identified emphysema among 2,674 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study. The patients had CT scans at a mean age of 50 and spirometry at a mean age of 55.
 

Racial differences

The investigators found that among men with forced expiratory volume in 1 second (FEV1) ranging from 100% to 120% of predicted according to race-adjusted formulas, 14.6% of Black men had emphysema, compared with only 1.7% of White men (P < .001). Respective emphysema rates in Black women and White women were 3.8% and 1.9%; this difference was not statistically significant.

Among patients with FEV1 80% to 99% of predicted according to race-specific measures, 15.5% of Black men had emphysema, compared with 4% of White men (P < .001). Respective rates of emphysema were 6.9% for Black women versus 3.2% for White women (P = .025).

When the investigators applied race-neutral spirometry reference equations to the same population, they found that it attenuated but did not completely eliminate the racial disparity in emphysema prevalence among patients with FEV1, ranging from 80% to 120% of predicted.
 

Relic of the past

The results suggest that race-based adjustments of spirometry measures are a relic of less enlightened times, said Adam Gaffney, MD, MPH, assistant professor of medicine at Harvard Medical School, Boston, and a pulmonologist and critical care physician at Cambridge Health Alliance, Massachusetts.

“If the average lower lung function of Black people is being driven by adversity, structural racism, and deprivation, that means that race-specific equations are normalizing that adversity,” he said in an interview.

“In my opinion, it is time to move beyond race-based equations in clinical pulmonary medicine, particularly in the context of patients with established lung disease in whom use of race-based equations might actually lead to undertreatment,” said Dr. Gaffney, who was not involved in the study.

Dr. Liu agreed that it’s time to move to race-neutral measures and that the whole concept of race-based differences is flawed.

“The long-standing structural inequities in health likely made the reference populations have lower lung function than among Whites,” she told this news organization.

Dr. Liu said that evaluation of lung function should not rely on spirometry alone, but should also include – when appropriate – CT scans, as well as improved understanding of how symptoms may be predictive for poor outcomes.

The study was supported by grants from the National Institutes of Health. Dr. Liu and Dr. Gaffney have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Regardless of the severity of their initial illness, 89% of people who were hospitalized with COVID-19 had returned to their original work 2 years later, a new study shows.

The burden of persistent COVID-19 symptoms appeared to improve over time, but a higher percentage of former patients reported poor health, compared with the general population. This suggests that some patients need more time to completely recover from COVID-19, wrote the authors of the new study, which was published in The Lancet Respiratory Medicine. Previous research has shown that the health effects of COVID-19 last for up to a year, but data from longer-term studies are limited, said Lixue Huang, MD, of Capital Medical University, Beijing, one of the study authors, and colleagues.

Methods and results

In the new study, the researchers reviewed data from 1,192 adult patients who were discharged from the hospital after surviving COVID-19 between Jan. 7, 2020, and May 29, 2020. The researchers measured the participants’ health outcomes at 6 months, 12 months, and 2 years after their onset of symptoms. A community-based dataset of 3,383 adults with no history of COVID-19 served as controls to measure the recovery of the COVID-19 patients. The median age of the patients at the time of hospital discharge was 57 years, and 46% were women. The median follow-up time after the onset of symptoms was 185 days, 349 days, and 685 days for the 6-month, 12-month, and 2-year visits, respectively. The researchers measured health outcomes using a 6-min walking distance (6MWD) test, laboratory tests, and questionnaires about symptoms, mental health, health-related quality of life, returning to work, and health care use since leaving the hospital.

Overall, the proportion of COVID-19 survivors with at least one symptom decreased from 68% at 6 months to 55% at 2 years (P < .0001). The most frequent symptoms were fatigue and muscle weakness, reported by approximately one-third of the patients (31%); sleep problems also were reported by 31% of the patients.

The proportion of individuals with poor results on the 6MWD decreased continuously over time, not only in COVID-19 survivors overall, but also in three subgroups of varying initial disease severity. Of the 494 survivors who reported working before becoming ill, 438 (89%) had returned to their original jobs 2 years later. The most common reasons for not returning to work were decreased physical function, unwillingness to return, and unemployment, the researchers noted.

However, at 2 years, COVID-19 survivors reported more pain and discomfort, as well as more anxiety and depression, compared with the controls (23% vs. 5% and 12% vs. 5%, respectively).

In addition, significantly more survivors who needed high levels of respiratory support while hospitalized had lung diffusion impairment (65%), reduced residual volume (62%), and total lung capacity (39%), compared with matched controls (36%, 20%, and 6%, respectively) at 2 years.

Long-COVID concerns

Approximately half of the survivors had symptoms of long COVID at 2 years. These individuals were more likely to report pain or discomfort or anxiety or depression, as well as mobility problems, compared to survivors without long COVID. Participants with long-COVID symptoms were more than twice as likely to have an outpatient clinic visit (odds ratio, 2.82), and not quite twice as likely to be rehospitalized (OR, 1.64).

“We found that [health-related quality of life], exercise capacity, and mental health continued to improve throughout the 2 years regardless of initial disease severity, but about half still had symptomatic sequelae at 2 years,” the researchers wrote in their paper.

Findings can inform doctor-patient discussions

“We are increasingly recognizing that the health effects of COVID-19 may persist beyond acute illness, therefore this is a timely study to assess the long-term impact of COVID-19 with a long follow-up period,” said Suman Pal, MD, an internal medicine physician at the University of New Mexico, Albuquerque, in an interview.

The findings are consistent with the existing literature, said Dr. Pal, who was not involved in the study.  The data from the study “can help clinicians have discussions regarding expected recovery and long-term prognosis for patients with COVID-19,” he noted.

What patients should know is that “studies such as this can help COVID-19 survivors understand and monitor persistent symptoms they may experience, and bring them to the attention of their clinicians,” said Dr. Pal.

However, “As a single-center study with high attrition of subjects during the study period, the findings may not be generalizable,” Dr. Pal emphasized. “Larger-scale studies and patient registries distributed over different geographical areas and time periods will help obtain a better understanding of the nature and prevalence of long COVID,” he said.

The study findings were limited by several factors, including the lack of formerly hospitalized controls with respiratory infections other than COVID-19 to determine which outcomes are COVID-19 specific, the researchers noted. Other limitations included the use of data from only patients at a single center, and from the early stages of the pandemic, as well as the use of self-reports for comorbidities and health outcomes, they said.

However, the results represent the longest-known published longitudinal follow-up of patients who recovered from acute COVID-19, the researchers emphasized. Study strengths included the large sample size, longitudinal design, and long-term follow-up with non-COVID controls to determine outcomes. The researchers noted their plans to conduct annual follow-ups in the current study population. They added that more research is needed to explore rehabilitation programs to promote recovery for COVID-19 survivors and to reduce the effects of long COVID.

The study was supported by the Chinese Academy of Medical Sciences, National Natural Science Foundation of China, National Key Research and Development Program of China, National Administration of Traditional Chinese Medicine, Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis, China Evergrande Group, Jack Ma Foundation, Sino Biopharmaceutical, Ping An Insurance (Group), and New Sunshine Charity Foundation. The researchers and Dr. Pal had no financial conflicts to disclose.

This article was updated on 5/16/2022.

Regardless of the severity of their initial illness, 89% of people who were hospitalized with COVID-19 had returned to their original work 2 years later, a new study shows.

The burden of persistent COVID-19 symptoms appeared to improve over time, but a higher percentage of former patients reported poor health, compared with the general population. This suggests that some patients need more time to completely recover from COVID-19, wrote the authors of the new study, which was published in The Lancet Respiratory Medicine. Previous research has shown that the health effects of COVID-19 last for up to a year, but data from longer-term studies are limited, said Lixue Huang, MD, of Capital Medical University, Beijing, one of the study authors, and colleagues.

Methods and results

In the new study, the researchers reviewed data from 1,192 adult patients who were discharged from the hospital after surviving COVID-19 between Jan. 7, 2020, and May 29, 2020. The researchers measured the participants’ health outcomes at 6 months, 12 months, and 2 years after their onset of symptoms. A community-based dataset of 3,383 adults with no history of COVID-19 served as controls to measure the recovery of the COVID-19 patients. The median age of the patients at the time of hospital discharge was 57 years, and 46% were women. The median follow-up time after the onset of symptoms was 185 days, 349 days, and 685 days for the 6-month, 12-month, and 2-year visits, respectively. The researchers measured health outcomes using a 6-min walking distance (6MWD) test, laboratory tests, and questionnaires about symptoms, mental health, health-related quality of life, returning to work, and health care use since leaving the hospital.

Overall, the proportion of COVID-19 survivors with at least one symptom decreased from 68% at 6 months to 55% at 2 years (P < .0001). The most frequent symptoms were fatigue and muscle weakness, reported by approximately one-third of the patients (31%); sleep problems also were reported by 31% of the patients.

The proportion of individuals with poor results on the 6MWD decreased continuously over time, not only in COVID-19 survivors overall, but also in three subgroups of varying initial disease severity. Of the 494 survivors who reported working before becoming ill, 438 (89%) had returned to their original jobs 2 years later. The most common reasons for not returning to work were decreased physical function, unwillingness to return, and unemployment, the researchers noted.

However, at 2 years, COVID-19 survivors reported more pain and discomfort, as well as more anxiety and depression, compared with the controls (23% vs. 5% and 12% vs. 5%, respectively).

In addition, significantly more survivors who needed high levels of respiratory support while hospitalized had lung diffusion impairment (65%), reduced residual volume (62%), and total lung capacity (39%), compared with matched controls (36%, 20%, and 6%, respectively) at 2 years.

Long-COVID concerns

Approximately half of the survivors had symptoms of long COVID at 2 years. These individuals were more likely to report pain or discomfort or anxiety or depression, as well as mobility problems, compared to survivors without long COVID. Participants with long-COVID symptoms were more than twice as likely to have an outpatient clinic visit (odds ratio, 2.82), and not quite twice as likely to be rehospitalized (OR, 1.64).

“We found that [health-related quality of life], exercise capacity, and mental health continued to improve throughout the 2 years regardless of initial disease severity, but about half still had symptomatic sequelae at 2 years,” the researchers wrote in their paper.

Findings can inform doctor-patient discussions

“We are increasingly recognizing that the health effects of COVID-19 may persist beyond acute illness, therefore this is a timely study to assess the long-term impact of COVID-19 with a long follow-up period,” said Suman Pal, MD, an internal medicine physician at the University of New Mexico, Albuquerque, in an interview.

The findings are consistent with the existing literature, said Dr. Pal, who was not involved in the study.  The data from the study “can help clinicians have discussions regarding expected recovery and long-term prognosis for patients with COVID-19,” he noted.

What patients should know is that “studies such as this can help COVID-19 survivors understand and monitor persistent symptoms they may experience, and bring them to the attention of their clinicians,” said Dr. Pal.

However, “As a single-center study with high attrition of subjects during the study period, the findings may not be generalizable,” Dr. Pal emphasized. “Larger-scale studies and patient registries distributed over different geographical areas and time periods will help obtain a better understanding of the nature and prevalence of long COVID,” he said.

The study findings were limited by several factors, including the lack of formerly hospitalized controls with respiratory infections other than COVID-19 to determine which outcomes are COVID-19 specific, the researchers noted. Other limitations included the use of data from only patients at a single center, and from the early stages of the pandemic, as well as the use of self-reports for comorbidities and health outcomes, they said.

However, the results represent the longest-known published longitudinal follow-up of patients who recovered from acute COVID-19, the researchers emphasized. Study strengths included the large sample size, longitudinal design, and long-term follow-up with non-COVID controls to determine outcomes. The researchers noted their plans to conduct annual follow-ups in the current study population. They added that more research is needed to explore rehabilitation programs to promote recovery for COVID-19 survivors and to reduce the effects of long COVID.

The study was supported by the Chinese Academy of Medical Sciences, National Natural Science Foundation of China, National Key Research and Development Program of China, National Administration of Traditional Chinese Medicine, Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis, China Evergrande Group, Jack Ma Foundation, Sino Biopharmaceutical, Ping An Insurance (Group), and New Sunshine Charity Foundation. The researchers and Dr. Pal had no financial conflicts to disclose.

This article was updated on 5/16/2022.

Regardless of the severity of their initial illness, 89% of people who were hospitalized with COVID-19 had returned to their original work 2 years later, a new study shows.

The burden of persistent COVID-19 symptoms appeared to improve over time, but a higher percentage of former patients reported poor health, compared with the general population. This suggests that some patients need more time to completely recover from COVID-19, wrote the authors of the new study, which was published in The Lancet Respiratory Medicine. Previous research has shown that the health effects of COVID-19 last for up to a year, but data from longer-term studies are limited, said Lixue Huang, MD, of Capital Medical University, Beijing, one of the study authors, and colleagues.

Methods and results

In the new study, the researchers reviewed data from 1,192 adult patients who were discharged from the hospital after surviving COVID-19 between Jan. 7, 2020, and May 29, 2020. The researchers measured the participants’ health outcomes at 6 months, 12 months, and 2 years after their onset of symptoms. A community-based dataset of 3,383 adults with no history of COVID-19 served as controls to measure the recovery of the COVID-19 patients. The median age of the patients at the time of hospital discharge was 57 years, and 46% were women. The median follow-up time after the onset of symptoms was 185 days, 349 days, and 685 days for the 6-month, 12-month, and 2-year visits, respectively. The researchers measured health outcomes using a 6-min walking distance (6MWD) test, laboratory tests, and questionnaires about symptoms, mental health, health-related quality of life, returning to work, and health care use since leaving the hospital.

Overall, the proportion of COVID-19 survivors with at least one symptom decreased from 68% at 6 months to 55% at 2 years (P < .0001). The most frequent symptoms were fatigue and muscle weakness, reported by approximately one-third of the patients (31%); sleep problems also were reported by 31% of the patients.

The proportion of individuals with poor results on the 6MWD decreased continuously over time, not only in COVID-19 survivors overall, but also in three subgroups of varying initial disease severity. Of the 494 survivors who reported working before becoming ill, 438 (89%) had returned to their original jobs 2 years later. The most common reasons for not returning to work were decreased physical function, unwillingness to return, and unemployment, the researchers noted.

However, at 2 years, COVID-19 survivors reported more pain and discomfort, as well as more anxiety and depression, compared with the controls (23% vs. 5% and 12% vs. 5%, respectively).

In addition, significantly more survivors who needed high levels of respiratory support while hospitalized had lung diffusion impairment (65%), reduced residual volume (62%), and total lung capacity (39%), compared with matched controls (36%, 20%, and 6%, respectively) at 2 years.

Long-COVID concerns

Approximately half of the survivors had symptoms of long COVID at 2 years. These individuals were more likely to report pain or discomfort or anxiety or depression, as well as mobility problems, compared to survivors without long COVID. Participants with long-COVID symptoms were more than twice as likely to have an outpatient clinic visit (odds ratio, 2.82), and not quite twice as likely to be rehospitalized (OR, 1.64).

“We found that [health-related quality of life], exercise capacity, and mental health continued to improve throughout the 2 years regardless of initial disease severity, but about half still had symptomatic sequelae at 2 years,” the researchers wrote in their paper.

Findings can inform doctor-patient discussions

“We are increasingly recognizing that the health effects of COVID-19 may persist beyond acute illness, therefore this is a timely study to assess the long-term impact of COVID-19 with a long follow-up period,” said Suman Pal, MD, an internal medicine physician at the University of New Mexico, Albuquerque, in an interview.

The findings are consistent with the existing literature, said Dr. Pal, who was not involved in the study.  The data from the study “can help clinicians have discussions regarding expected recovery and long-term prognosis for patients with COVID-19,” he noted.

What patients should know is that “studies such as this can help COVID-19 survivors understand and monitor persistent symptoms they may experience, and bring them to the attention of their clinicians,” said Dr. Pal.

However, “As a single-center study with high attrition of subjects during the study period, the findings may not be generalizable,” Dr. Pal emphasized. “Larger-scale studies and patient registries distributed over different geographical areas and time periods will help obtain a better understanding of the nature and prevalence of long COVID,” he said.

The study findings were limited by several factors, including the lack of formerly hospitalized controls with respiratory infections other than COVID-19 to determine which outcomes are COVID-19 specific, the researchers noted. Other limitations included the use of data from only patients at a single center, and from the early stages of the pandemic, as well as the use of self-reports for comorbidities and health outcomes, they said.

However, the results represent the longest-known published longitudinal follow-up of patients who recovered from acute COVID-19, the researchers emphasized. Study strengths included the large sample size, longitudinal design, and long-term follow-up with non-COVID controls to determine outcomes. The researchers noted their plans to conduct annual follow-ups in the current study population. They added that more research is needed to explore rehabilitation programs to promote recovery for COVID-19 survivors and to reduce the effects of long COVID.

The study was supported by the Chinese Academy of Medical Sciences, National Natural Science Foundation of China, National Key Research and Development Program of China, National Administration of Traditional Chinese Medicine, Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis, China Evergrande Group, Jack Ma Foundation, Sino Biopharmaceutical, Ping An Insurance (Group), and New Sunshine Charity Foundation. The researchers and Dr. Pal had no financial conflicts to disclose.

This article was updated on 5/16/2022.

All patients with idiopathic inflammatory myopathies (IIM) should be screened for swallowing difficulties, according to the first evidence-based guideline to be produced.

The guideline, which has been developed by a working group of the British Society for Rheumatology (BSR), also advises that all diagnosed patients should have their myositis antibody levels checked and have their overall well-being assessed. Other recommendations for all patients include the use of glucocorticoids to reduce muscle inflammation and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) for long-term treatment.

“Finally, now, we’re able to standardize the way we treat adults and children with IIM,” senior guideline author Hector Chinoy, PhD, said at the society’s annual meeting.

It has been a long labor of love, however, taking 4 years to get the guideline published, said Dr. Chinoy, professor of rheumatology and neuromuscular disease at the University of Manchester (England), and a consultant at Salford (England) Royal Hospital.

“We’re not covering diagnosis, classification, or the investigation of suspected IIM,” said Dr. Chinoy. Inclusion body myositis also is not included.

Altogether, there are 13 recommendations that have been developed using a PICO (patient or population, intervention, comparison, outcome) format, graded based on the quality of the available evidence, and then voted on by the working group members to give a score of the strength of agreement. Dr. Chinoy noted that there was a checklist included in the Supplementary Data section of the guideline to help follow the recommendations.

“The target audience for the guideline reflects the variety of clinicians caring for patients with IIM,” Dr. Chinoy said. So that is not just pediatric and adult rheumatologists, but also neurologists, dermatologists, respiratory physicians, oncologists, gastroenterologists, cardiologists, and of course other health care professionals. This includes rheumatology and neurology nurses, psychologists, speech and language therapists, and podiatrists, as well as rheumatology specialist pharmacists, physiotherapists, and occupational therapists.

With reference to the latter, Liza McCann, MBBS, who co-led the development of the guideline, said in a statement released by the BSR that the guideline “highlights the importance of exercise, led and monitored by specialist physiotherapists and occupational therapists.”

Dr. McCann, a consultant pediatric rheumatologist at Alder Hey Hospital, Liverpool, England, and Honorary Clinical Lecturer at the University of Liverpool, added that the guidelines also cover “the need to address psychological wellbeing as an integral part of treatment, in parallel with pharmacological therapies.”

Recommendation highlights

Some of the highlights of the recommendations include the use of high-dose glucocorticoids to manage skeletal muscle inflammation at the time of treatment induction, with specific guidance on the different doses to use in adults and in children. There also is guidance on the use of csDMARDs in both populations and what to use if there is refractory disease – with the strongest evidence supporting the use of intravenous immunoglobulin (IVIG) or cyclophosphamide, and possibly rituximab and abatacept.

“There is insufficient evidence to recommend JAK inhibition,” Dr. Chinoy said. The data search used to develop the guideline had a cutoff of October 2020, but even now there is only anecdotal evidence from case studies, he added.

Importantly, the guidelines recognize that childhood IIM differs from adult disease and call for children to be managed by pediatric specialists.

“Routine assessment of dysphagia should be considered in all patients,” Dr. Chinoy said, “so ask the question.” The recommendation is that a swallowing assessment should involve a speech and language therapist or gastroenterologist, and that IVIG be considered for active disease and dysphagia that is resistant to other treatments.

There also are recommendations to screen adult patients for interstitial lung disease, consider fracture risk, and screen adult patients for cancer if they have specific risk factors that include older age at onset, male gender, dysphagia, and rapid disease onset, among others.
 

Separate cancer screening guidelines on cards

“Around one in four patients with myositis will develop cancer within the 3 years either before or after myositis onset,” Alexander Oldroyd, MBChB, PhD, said in a separate presentation at the BSR annual meeting.

“It’s a hugely increased risk compared to the general population, and a great worry for patients,” he added. Exactly why there is an increased risk is not known, but “there’s a big link between the biological onset of cancer and myositis.”

Dr. Oldroyd, who is an NIHR Academic Clinical Lecturer at the University of Manchester in England and a coauthor of the BSR myositis guideline, is part of a special interest group set up by the International Myositis Assessment and Clinical Studies Group (IMACS) that is in the process of developing separate guidelines for cancer screening in people newly diagnosed with IIM.

The aim was to produce evidence-based recommendations that were both “pragmatic and practical,” that could help clinicians answer patient’s questions on their risk and how best and how often to screen them, Dr. Oldroyd explained. Importantly, IMACS has endeavored to create recommendations that should be applicable across different countries and health care systems.

“We had to acknowledge that there’s not a lot of evidence base there,” Dr. Oldroyd said, noting that he and colleagues conducted a systematic literature review and meta-analysis and used a Delphi process to draft 20 recommendations. These cover identifying risk factors for cancer in people with myositis and categorizing people into low, medium, and high-risk categories. The recommendations also cover what should constitute basic and enhanced screening, and how often someone should be screened.

Moreover, the authors make recommendations on the use of imaging modalities such as PET and CT scans, as well as upper and lower gastrointestinal endoscopy and naso-endoscopy.

“As rheumatologists, we don’t talk about cancer a lot,” Dr. Oldroyd said. “We pick up a lot of incidental cancers, but we don’t usually talk about cancer screening with patients.” That’s something that needs to change, he said.

“It’s important – just get it out in the open, talk to people about it,” Dr. Oldroyd said.

“Tell them what you’re wanting to do, how you’re wanting to investigate for it, clearly communicate their risk,” he said. “But also acknowledge the limited evidence as well, and clearly communicate the results.”

Dr. Chinoy acknowledged he had received fees for presentations (UCB, Biogen), consultancy (Alexion, Novartis, Eli Lilly, Orphazyme, AstraZeneca), or grant support (Eli Lilly, UCB) that had been paid via his institution for the purpose of furthering myositis research. Dr. Oldroyd had no conflicts of interest to disclose.

All patients with idiopathic inflammatory myopathies (IIM) should be screened for swallowing difficulties, according to the first evidence-based guideline to be produced.

The guideline, which has been developed by a working group of the British Society for Rheumatology (BSR), also advises that all diagnosed patients should have their myositis antibody levels checked and have their overall well-being assessed. Other recommendations for all patients include the use of glucocorticoids to reduce muscle inflammation and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) for long-term treatment.

“Finally, now, we’re able to standardize the way we treat adults and children with IIM,” senior guideline author Hector Chinoy, PhD, said at the society’s annual meeting.

It has been a long labor of love, however, taking 4 years to get the guideline published, said Dr. Chinoy, professor of rheumatology and neuromuscular disease at the University of Manchester (England), and a consultant at Salford (England) Royal Hospital.

“We’re not covering diagnosis, classification, or the investigation of suspected IIM,” said Dr. Chinoy. Inclusion body myositis also is not included.

Altogether, there are 13 recommendations that have been developed using a PICO (patient or population, intervention, comparison, outcome) format, graded based on the quality of the available evidence, and then voted on by the working group members to give a score of the strength of agreement. Dr. Chinoy noted that there was a checklist included in the Supplementary Data section of the guideline to help follow the recommendations.

“The target audience for the guideline reflects the variety of clinicians caring for patients with IIM,” Dr. Chinoy said. So that is not just pediatric and adult rheumatologists, but also neurologists, dermatologists, respiratory physicians, oncologists, gastroenterologists, cardiologists, and of course other health care professionals. This includes rheumatology and neurology nurses, psychologists, speech and language therapists, and podiatrists, as well as rheumatology specialist pharmacists, physiotherapists, and occupational therapists.

With reference to the latter, Liza McCann, MBBS, who co-led the development of the guideline, said in a statement released by the BSR that the guideline “highlights the importance of exercise, led and monitored by specialist physiotherapists and occupational therapists.”

Dr. McCann, a consultant pediatric rheumatologist at Alder Hey Hospital, Liverpool, England, and Honorary Clinical Lecturer at the University of Liverpool, added that the guidelines also cover “the need to address psychological wellbeing as an integral part of treatment, in parallel with pharmacological therapies.”

Recommendation highlights

Some of the highlights of the recommendations include the use of high-dose glucocorticoids to manage skeletal muscle inflammation at the time of treatment induction, with specific guidance on the different doses to use in adults and in children. There also is guidance on the use of csDMARDs in both populations and what to use if there is refractory disease – with the strongest evidence supporting the use of intravenous immunoglobulin (IVIG) or cyclophosphamide, and possibly rituximab and abatacept.

“There is insufficient evidence to recommend JAK inhibition,” Dr. Chinoy said. The data search used to develop the guideline had a cutoff of October 2020, but even now there is only anecdotal evidence from case studies, he added.

Importantly, the guidelines recognize that childhood IIM differs from adult disease and call for children to be managed by pediatric specialists.

“Routine assessment of dysphagia should be considered in all patients,” Dr. Chinoy said, “so ask the question.” The recommendation is that a swallowing assessment should involve a speech and language therapist or gastroenterologist, and that IVIG be considered for active disease and dysphagia that is resistant to other treatments.

There also are recommendations to screen adult patients for interstitial lung disease, consider fracture risk, and screen adult patients for cancer if they have specific risk factors that include older age at onset, male gender, dysphagia, and rapid disease onset, among others.
 

Separate cancer screening guidelines on cards

“Around one in four patients with myositis will develop cancer within the 3 years either before or after myositis onset,” Alexander Oldroyd, MBChB, PhD, said in a separate presentation at the BSR annual meeting.

“It’s a hugely increased risk compared to the general population, and a great worry for patients,” he added. Exactly why there is an increased risk is not known, but “there’s a big link between the biological onset of cancer and myositis.”

Dr. Oldroyd, who is an NIHR Academic Clinical Lecturer at the University of Manchester in England and a coauthor of the BSR myositis guideline, is part of a special interest group set up by the International Myositis Assessment and Clinical Studies Group (IMACS) that is in the process of developing separate guidelines for cancer screening in people newly diagnosed with IIM.

The aim was to produce evidence-based recommendations that were both “pragmatic and practical,” that could help clinicians answer patient’s questions on their risk and how best and how often to screen them, Dr. Oldroyd explained. Importantly, IMACS has endeavored to create recommendations that should be applicable across different countries and health care systems.

“We had to acknowledge that there’s not a lot of evidence base there,” Dr. Oldroyd said, noting that he and colleagues conducted a systematic literature review and meta-analysis and used a Delphi process to draft 20 recommendations. These cover identifying risk factors for cancer in people with myositis and categorizing people into low, medium, and high-risk categories. The recommendations also cover what should constitute basic and enhanced screening, and how often someone should be screened.

Moreover, the authors make recommendations on the use of imaging modalities such as PET and CT scans, as well as upper and lower gastrointestinal endoscopy and naso-endoscopy.

“As rheumatologists, we don’t talk about cancer a lot,” Dr. Oldroyd said. “We pick up a lot of incidental cancers, but we don’t usually talk about cancer screening with patients.” That’s something that needs to change, he said.

“It’s important – just get it out in the open, talk to people about it,” Dr. Oldroyd said.

“Tell them what you’re wanting to do, how you’re wanting to investigate for it, clearly communicate their risk,” he said. “But also acknowledge the limited evidence as well, and clearly communicate the results.”

Dr. Chinoy acknowledged he had received fees for presentations (UCB, Biogen), consultancy (Alexion, Novartis, Eli Lilly, Orphazyme, AstraZeneca), or grant support (Eli Lilly, UCB) that had been paid via his institution for the purpose of furthering myositis research. Dr. Oldroyd had no conflicts of interest to disclose.

All patients with idiopathic inflammatory myopathies (IIM) should be screened for swallowing difficulties, according to the first evidence-based guideline to be produced.

The guideline, which has been developed by a working group of the British Society for Rheumatology (BSR), also advises that all diagnosed patients should have their myositis antibody levels checked and have their overall well-being assessed. Other recommendations for all patients include the use of glucocorticoids to reduce muscle inflammation and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) for long-term treatment.

“Finally, now, we’re able to standardize the way we treat adults and children with IIM,” senior guideline author Hector Chinoy, PhD, said at the society’s annual meeting.

It has been a long labor of love, however, taking 4 years to get the guideline published, said Dr. Chinoy, professor of rheumatology and neuromuscular disease at the University of Manchester (England), and a consultant at Salford (England) Royal Hospital.

“We’re not covering diagnosis, classification, or the investigation of suspected IIM,” said Dr. Chinoy. Inclusion body myositis also is not included.

Altogether, there are 13 recommendations that have been developed using a PICO (patient or population, intervention, comparison, outcome) format, graded based on the quality of the available evidence, and then voted on by the working group members to give a score of the strength of agreement. Dr. Chinoy noted that there was a checklist included in the Supplementary Data section of the guideline to help follow the recommendations.

“The target audience for the guideline reflects the variety of clinicians caring for patients with IIM,” Dr. Chinoy said. So that is not just pediatric and adult rheumatologists, but also neurologists, dermatologists, respiratory physicians, oncologists, gastroenterologists, cardiologists, and of course other health care professionals. This includes rheumatology and neurology nurses, psychologists, speech and language therapists, and podiatrists, as well as rheumatology specialist pharmacists, physiotherapists, and occupational therapists.

With reference to the latter, Liza McCann, MBBS, who co-led the development of the guideline, said in a statement released by the BSR that the guideline “highlights the importance of exercise, led and monitored by specialist physiotherapists and occupational therapists.”

Dr. McCann, a consultant pediatric rheumatologist at Alder Hey Hospital, Liverpool, England, and Honorary Clinical Lecturer at the University of Liverpool, added that the guidelines also cover “the need to address psychological wellbeing as an integral part of treatment, in parallel with pharmacological therapies.”

Recommendation highlights

Some of the highlights of the recommendations include the use of high-dose glucocorticoids to manage skeletal muscle inflammation at the time of treatment induction, with specific guidance on the different doses to use in adults and in children. There also is guidance on the use of csDMARDs in both populations and what to use if there is refractory disease – with the strongest evidence supporting the use of intravenous immunoglobulin (IVIG) or cyclophosphamide, and possibly rituximab and abatacept.

“There is insufficient evidence to recommend JAK inhibition,” Dr. Chinoy said. The data search used to develop the guideline had a cutoff of October 2020, but even now there is only anecdotal evidence from case studies, he added.

Importantly, the guidelines recognize that childhood IIM differs from adult disease and call for children to be managed by pediatric specialists.

“Routine assessment of dysphagia should be considered in all patients,” Dr. Chinoy said, “so ask the question.” The recommendation is that a swallowing assessment should involve a speech and language therapist or gastroenterologist, and that IVIG be considered for active disease and dysphagia that is resistant to other treatments.

There also are recommendations to screen adult patients for interstitial lung disease, consider fracture risk, and screen adult patients for cancer if they have specific risk factors that include older age at onset, male gender, dysphagia, and rapid disease onset, among others.
 

Separate cancer screening guidelines on cards

“Around one in four patients with myositis will develop cancer within the 3 years either before or after myositis onset,” Alexander Oldroyd, MBChB, PhD, said in a separate presentation at the BSR annual meeting.

“It’s a hugely increased risk compared to the general population, and a great worry for patients,” he added. Exactly why there is an increased risk is not known, but “there’s a big link between the biological onset of cancer and myositis.”

Dr. Oldroyd, who is an NIHR Academic Clinical Lecturer at the University of Manchester in England and a coauthor of the BSR myositis guideline, is part of a special interest group set up by the International Myositis Assessment and Clinical Studies Group (IMACS) that is in the process of developing separate guidelines for cancer screening in people newly diagnosed with IIM.

The aim was to produce evidence-based recommendations that were both “pragmatic and practical,” that could help clinicians answer patient’s questions on their risk and how best and how often to screen them, Dr. Oldroyd explained. Importantly, IMACS has endeavored to create recommendations that should be applicable across different countries and health care systems.

“We had to acknowledge that there’s not a lot of evidence base there,” Dr. Oldroyd said, noting that he and colleagues conducted a systematic literature review and meta-analysis and used a Delphi process to draft 20 recommendations. These cover identifying risk factors for cancer in people with myositis and categorizing people into low, medium, and high-risk categories. The recommendations also cover what should constitute basic and enhanced screening, and how often someone should be screened.

Moreover, the authors make recommendations on the use of imaging modalities such as PET and CT scans, as well as upper and lower gastrointestinal endoscopy and naso-endoscopy.

“As rheumatologists, we don’t talk about cancer a lot,” Dr. Oldroyd said. “We pick up a lot of incidental cancers, but we don’t usually talk about cancer screening with patients.” That’s something that needs to change, he said.

“It’s important – just get it out in the open, talk to people about it,” Dr. Oldroyd said.

“Tell them what you’re wanting to do, how you’re wanting to investigate for it, clearly communicate their risk,” he said. “But also acknowledge the limited evidence as well, and clearly communicate the results.”

Dr. Chinoy acknowledged he had received fees for presentations (UCB, Biogen), consultancy (Alexion, Novartis, Eli Lilly, Orphazyme, AstraZeneca), or grant support (Eli Lilly, UCB) that had been paid via his institution for the purpose of furthering myositis research. Dr. Oldroyd had no conflicts of interest to disclose.

Reduced exercise capacity and peak ventilation were significant predictors of early mortality in adults with chronic obstructive pulmonary disease, based on data from 126 individuals.

Cardiopulmonary exercise testing (CPET) is a common assessment for cardiorespiratory disease patients, but its role as a predictor of clinically relevant outcomes in chronic obstructive pulmonary disease (COPD) has not been investigated, and data on changes in exercise capacity over time in COPD patients are limited, wrote Cassia da Luz Goulart, MD, of the Federal University of São Carlos, Brazil, and colleagues.

The researchers hypothesized that CPET threshold values could be used as predictors of mortality in COPD.

In a prospective study published in Respiratory Medicine, the researchers identified 126 adults with COPD who were followed for 42 months. At study entry, each patient completed a clinical evaluation, followed by a pulmonary function test and CPET. The average age of the patients was 65 years, and 73% were men. All patients were on optimal medical management for COPD.

The researchers recorded data on peak oxygen consumption (VO₂, mL/min), VCO₂ (mL/min), minute ventilation (VE, L/min), the oxygen uptake efficiency slope (OUES), and ventilatory efficiency (the VE/VCO₂ slope).

The participants performed CPET on a cycle ergometer, with breath-by-breath analysis measured throughout the test using a computer-based system.

A total of 48 patients (38%) died during the 42-month follow-up period. Overall, the significant predictors of mortality were VE/VCO₂ slope of 30 or higher, peak VE of 25.7 L/min, and peak VO₂ ≤ 13.8 mLO₂ kg^–1 min^–1 were strong predictors of mortality in COPD patients in a Cox regression analysis.

When comparing the 78 survivors to the 48 nonsurvivors, the researchers found that the nonsurvivors were significantly more likely to be women, with worse lung function, inspiratory muscle weakness, and poorer CPET responses (P < .050 for all).

“The VE peak response is directly related to the FEV₁ in COPD patients, factors such as dyspnea and increased leg discomfort negatively impact the VE response during exercise,” the researchers wrote in their discussion of the findings. In this context, our results may hold clinical utility in refining the prognostic accuracy when a patient with COPD has a VE peak ≤ 25.7 L/min,” they explained.

The study findings were limited by the inability to assess complete pulmonary function in the COPD patients, and the assessment only of three CPET measures, the researchers noted.

However, the results support the use of CPET as a clinical assessment tool for COPD patients, they said. “Moreover, therapeutic approaches, such as cardiopulmonary rehabilitation, may consider focusing on improving these metabolic and ventilatory markers as an indicator of clinical improvement and prognosis in patients with COPD,” they added.

The study was supported by the Fundação de Amparo a Pesquisa do Estado de São Paulo, Brazil, and by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brasil. The researchers had no financial conflicts to disclose.

Reduced exercise capacity and peak ventilation were significant predictors of early mortality in adults with chronic obstructive pulmonary disease, based on data from 126 individuals.

Cardiopulmonary exercise testing (CPET) is a common assessment for cardiorespiratory disease patients, but its role as a predictor of clinically relevant outcomes in chronic obstructive pulmonary disease (COPD) has not been investigated, and data on changes in exercise capacity over time in COPD patients are limited, wrote Cassia da Luz Goulart, MD, of the Federal University of São Carlos, Brazil, and colleagues.

The researchers hypothesized that CPET threshold values could be used as predictors of mortality in COPD.

In a prospective study published in Respiratory Medicine, the researchers identified 126 adults with COPD who were followed for 42 months. At study entry, each patient completed a clinical evaluation, followed by a pulmonary function test and CPET. The average age of the patients was 65 years, and 73% were men. All patients were on optimal medical management for COPD.

The researchers recorded data on peak oxygen consumption (VO₂, mL/min), VCO₂ (mL/min), minute ventilation (VE, L/min), the oxygen uptake efficiency slope (OUES), and ventilatory efficiency (the VE/VCO₂ slope).

The participants performed CPET on a cycle ergometer, with breath-by-breath analysis measured throughout the test using a computer-based system.

A total of 48 patients (38%) died during the 42-month follow-up period. Overall, the significant predictors of mortality were VE/VCO₂ slope of 30 or higher, peak VE of 25.7 L/min, and peak VO₂ ≤ 13.8 mLO₂ kg^–1 min^–1 were strong predictors of mortality in COPD patients in a Cox regression analysis.

When comparing the 78 survivors to the 48 nonsurvivors, the researchers found that the nonsurvivors were significantly more likely to be women, with worse lung function, inspiratory muscle weakness, and poorer CPET responses (P < .050 for all).

“The VE peak response is directly related to the FEV₁ in COPD patients, factors such as dyspnea and increased leg discomfort negatively impact the VE response during exercise,” the researchers wrote in their discussion of the findings. In this context, our results may hold clinical utility in refining the prognostic accuracy when a patient with COPD has a VE peak ≤ 25.7 L/min,” they explained.

The study findings were limited by the inability to assess complete pulmonary function in the COPD patients, and the assessment only of three CPET measures, the researchers noted.

However, the results support the use of CPET as a clinical assessment tool for COPD patients, they said. “Moreover, therapeutic approaches, such as cardiopulmonary rehabilitation, may consider focusing on improving these metabolic and ventilatory markers as an indicator of clinical improvement and prognosis in patients with COPD,” they added.

The study was supported by the Fundação de Amparo a Pesquisa do Estado de São Paulo, Brazil, and by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brasil. The researchers had no financial conflicts to disclose.

Reduced exercise capacity and peak ventilation were significant predictors of early mortality in adults with chronic obstructive pulmonary disease, based on data from 126 individuals.

Cardiopulmonary exercise testing (CPET) is a common assessment for cardiorespiratory disease patients, but its role as a predictor of clinically relevant outcomes in chronic obstructive pulmonary disease (COPD) has not been investigated, and data on changes in exercise capacity over time in COPD patients are limited, wrote Cassia da Luz Goulart, MD, of the Federal University of São Carlos, Brazil, and colleagues.

The researchers hypothesized that CPET threshold values could be used as predictors of mortality in COPD.

In a prospective study published in Respiratory Medicine, the researchers identified 126 adults with COPD who were followed for 42 months. At study entry, each patient completed a clinical evaluation, followed by a pulmonary function test and CPET. The average age of the patients was 65 years, and 73% were men. All patients were on optimal medical management for COPD.

The researchers recorded data on peak oxygen consumption (VO₂, mL/min), VCO₂ (mL/min), minute ventilation (VE, L/min), the oxygen uptake efficiency slope (OUES), and ventilatory efficiency (the VE/VCO₂ slope).

The participants performed CPET on a cycle ergometer, with breath-by-breath analysis measured throughout the test using a computer-based system.

A total of 48 patients (38%) died during the 42-month follow-up period. Overall, the significant predictors of mortality were VE/VCO₂ slope of 30 or higher, peak VE of 25.7 L/min, and peak VO₂ ≤ 13.8 mLO₂ kg^–1 min^–1 were strong predictors of mortality in COPD patients in a Cox regression analysis.

When comparing the 78 survivors to the 48 nonsurvivors, the researchers found that the nonsurvivors were significantly more likely to be women, with worse lung function, inspiratory muscle weakness, and poorer CPET responses (P < .050 for all).

“The VE peak response is directly related to the FEV₁ in COPD patients, factors such as dyspnea and increased leg discomfort negatively impact the VE response during exercise,” the researchers wrote in their discussion of the findings. In this context, our results may hold clinical utility in refining the prognostic accuracy when a patient with COPD has a VE peak ≤ 25.7 L/min,” they explained.

The study findings were limited by the inability to assess complete pulmonary function in the COPD patients, and the assessment only of three CPET measures, the researchers noted.

However, the results support the use of CPET as a clinical assessment tool for COPD patients, they said. “Moreover, therapeutic approaches, such as cardiopulmonary rehabilitation, may consider focusing on improving these metabolic and ventilatory markers as an indicator of clinical improvement and prognosis in patients with COPD,” they added.

The study was supported by the Fundação de Amparo a Pesquisa do Estado de São Paulo, Brazil, and by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brasil. The researchers had no financial conflicts to disclose.