Pulmonology

When asthma patients are having frequent clinical deteriorations, clinicians need to evaluate them for the presence and severity of bronchiectasis, according to the authors of a retrospective study in the Journal of Allergy and Clinical Immunology: In Practice. While bronchiectasis is known to worsen the clinical and functional outcomes in patients with asthma, data regarding the long-term effects of bronchiectasis on the clinical course of asthma have been limited, stated corresponding author Jung-Kyu Lee, MD, division of pulmonary and critical care medicine, Seoul (Republic of Korea) Metropolitan Government – Seoul National University.

Moderate to severe acute clinical deterioration risks were increased among the 251 patients (mean age 66.6 years, 77.2% men) with bronchiectasis out of 667 asthma patients included in the study. All studied patients underwent chest computed tomography and pulmonary function tests from 2013 to 2019 at two tertiary hospitals in Seoul. The primary outcome, annual incidence of moderate to severe acute exacerbations requiring additional treatment (systemic steroids, antibiotics, or both), was significantly higher in patients with bronchiectasis after a mean follow-up period of 3.96 years. Compared with patients who did not exhibit bronchiectasis, the annual rates of severe exacerbations (0.15 ± 0.43 vs. 0.08 ± 0.27; P = .010), moderate to severe (0.47 ± 0.79 vs. 0.34 ± 0.63; P = .018), and acute exacerbations during the follow-up period (49.8% vs. 39.4%; P = .009) were all significantly higher. There was no difference in the proportion of frequent exacerbators between the two groups, however. Severe acute exacerbations leading to hospitalizations, also, were more frequent in the group with bronchiectasis.
 

Risk factors explored

Significant factors conferring greater risk of severe and moderate to severe acute exacerbations in multivariable analysis included low body mass index, low baseline forced expiratory volume in 1 second (FEV₁), high use of inhaled corticosteroids, high medication possession, and high neutrophil/lymphocyte ratios. The existence of bronchiectasis remained an independent risk factor for severe and moderate to severe acute exacerbations despite adjustment for all other factors. While bronchiectasis score showed no association with annual rate of acute exacerbation, progression of bronchiectasis confirmed on follow-up CT was associated with increased risks of severe and moderate to severe acute exacerbation.

Included patients had a diagnosis of asthma confirmed by variable expiratory airflow limitation with pulmonary function tests (that is, positive bronchodilator response, positive bronchial provocation test, or excessive variation in lung function between visits). Past histories of tuberculosis and nontuberculous mycobacterial lung disease, lower absolute and predicted values of both baseline FEV₁ and forced vital capacity were more common among patients with bronchiectasis.

Dividing the study population into a group that had at least one moderate to severe acute exacerbation during the follow-up period and a group that did not, the researchers identified characteristics shared by exacerbators: a greater proportion were women, they had lower forced vital capacity and lung-diffusing capacity for carbon monoxide, higher blood FVC and blood neutrophil/lymphocyte ratio, and more medication use (inhaled corticosteroids, long-acting antimuscarinic agent, leukotriene-receptor antagonist, and methylxanthine), compared with the nonexacerbators. More bronchiectasis, more severe bronchiectasis (higher bronchiectasis score), and more progression of bronchiectasis were common among the exacerbators.

Higher acute exacerbation risks accompanied bronchiectasis, at 1.47-fold for moderate, 1.72-fold for severe, and 1.50-fold for moderate to severe exacerbations. Higher risk for severe and moderate to severe exacerbations was conferred by bronchiectasis progression, also.

The researchers pointed to contradictory effects of inhaled corticosteroid use, noting both corticosteroids’ essential role in controlling airway inflammation and hyperresponsiveness, exacerbations, and lung-function decline in asthma patients and that longer or greater inhaled corticosteroid use is associated with both clinical deterioration in asthma and bronchiectasis, and exacerbation history. For bronchiectasis, however, inhaled corticosteroid use offers no benefit while increasing susceptibility to infection and its risks through partial immunosuppression.

“Considering these contradictory effects of inhaled corticosteroid use, further research is needed regarding its risks and benefits in asthma patients with bronchiectasis, including differences in the benefit of inhaled corticosteroid use according to patient phenotype,” Dr. Kim and his colleagues concluded.
 

The role of corticosteroids

“One of the more important points discussed in this observational cohort study is the role of inhaled corticosteroid use in bronchiectasis,” said Mary Jo Farmer, MD, PhD, director of pulmonary hypertension services, Baystate Health, and assistant professor of medicine, University of Massachusetts – Baystate, both in Springfield, in an interview with this news organization. She cited a review finding no significant benefit versus placebo in spirometry, exacerbation rate, or sputum volume in the Cochrane Database of Systematic Reviews and another suggesting that quality of life was improved with inhaled corticosteroid use in individuals with blood eosinophils greater than 3%, compared with those not using inhaled corticosteroids or having lower eosinophil counts in the European Respiratory Journal. She cited also higher percentages (48% versus 23%) of adrenal insufficiency in bronchiectasis patients among those taking inhaled corticosteroids versus those not taking them.

Dr. Farmer added, “According to the 2018 Cochrane review of inhaled corticosteroid treatment for non–cystic fibrosis bronchiectasis, results from most randomized, placebo-controlled trials have been disappointing in terms of effects on most endpoints such as pulmonary function and exacerbation frequency. As such, the European Respiratory Society guidelines for the management of adult bronchiectasis advise against prescribing inhaled corticosteroids to patients with bronchiectasis, unless otherwise indicated by either an asthma or chronic obstructive pulmonary disease diagnosis. Also, inhaled corticosteroid treatment in asthma and COPD is associated with common side effects such as oral candidiasis, dysphonia and, in some cases, systemic corticosteroid effects. The rate of adverse events from inhaled corticosteroid treatment of bronchiectasis, however, is largely unknown.Dr. Lee and Dr. Farmer reported no relevant financial relationships. The study was independently supported.

When asthma patients are having frequent clinical deteriorations, clinicians need to evaluate them for the presence and severity of bronchiectasis, according to the authors of a retrospective study in the Journal of Allergy and Clinical Immunology: In Practice. While bronchiectasis is known to worsen the clinical and functional outcomes in patients with asthma, data regarding the long-term effects of bronchiectasis on the clinical course of asthma have been limited, stated corresponding author Jung-Kyu Lee, MD, division of pulmonary and critical care medicine, Seoul (Republic of Korea) Metropolitan Government – Seoul National University.

Moderate to severe acute clinical deterioration risks were increased among the 251 patients (mean age 66.6 years, 77.2% men) with bronchiectasis out of 667 asthma patients included in the study. All studied patients underwent chest computed tomography and pulmonary function tests from 2013 to 2019 at two tertiary hospitals in Seoul. The primary outcome, annual incidence of moderate to severe acute exacerbations requiring additional treatment (systemic steroids, antibiotics, or both), was significantly higher in patients with bronchiectasis after a mean follow-up period of 3.96 years. Compared with patients who did not exhibit bronchiectasis, the annual rates of severe exacerbations (0.15 ± 0.43 vs. 0.08 ± 0.27; P = .010), moderate to severe (0.47 ± 0.79 vs. 0.34 ± 0.63; P = .018), and acute exacerbations during the follow-up period (49.8% vs. 39.4%; P = .009) were all significantly higher. There was no difference in the proportion of frequent exacerbators between the two groups, however. Severe acute exacerbations leading to hospitalizations, also, were more frequent in the group with bronchiectasis.
 

Risk factors explored

Significant factors conferring greater risk of severe and moderate to severe acute exacerbations in multivariable analysis included low body mass index, low baseline forced expiratory volume in 1 second (FEV₁), high use of inhaled corticosteroids, high medication possession, and high neutrophil/lymphocyte ratios. The existence of bronchiectasis remained an independent risk factor for severe and moderate to severe acute exacerbations despite adjustment for all other factors. While bronchiectasis score showed no association with annual rate of acute exacerbation, progression of bronchiectasis confirmed on follow-up CT was associated with increased risks of severe and moderate to severe acute exacerbation.

Included patients had a diagnosis of asthma confirmed by variable expiratory airflow limitation with pulmonary function tests (that is, positive bronchodilator response, positive bronchial provocation test, or excessive variation in lung function between visits). Past histories of tuberculosis and nontuberculous mycobacterial lung disease, lower absolute and predicted values of both baseline FEV₁ and forced vital capacity were more common among patients with bronchiectasis.

Dividing the study population into a group that had at least one moderate to severe acute exacerbation during the follow-up period and a group that did not, the researchers identified characteristics shared by exacerbators: a greater proportion were women, they had lower forced vital capacity and lung-diffusing capacity for carbon monoxide, higher blood FVC and blood neutrophil/lymphocyte ratio, and more medication use (inhaled corticosteroids, long-acting antimuscarinic agent, leukotriene-receptor antagonist, and methylxanthine), compared with the nonexacerbators. More bronchiectasis, more severe bronchiectasis (higher bronchiectasis score), and more progression of bronchiectasis were common among the exacerbators.

Higher acute exacerbation risks accompanied bronchiectasis, at 1.47-fold for moderate, 1.72-fold for severe, and 1.50-fold for moderate to severe exacerbations. Higher risk for severe and moderate to severe exacerbations was conferred by bronchiectasis progression, also.

The researchers pointed to contradictory effects of inhaled corticosteroid use, noting both corticosteroids’ essential role in controlling airway inflammation and hyperresponsiveness, exacerbations, and lung-function decline in asthma patients and that longer or greater inhaled corticosteroid use is associated with both clinical deterioration in asthma and bronchiectasis, and exacerbation history. For bronchiectasis, however, inhaled corticosteroid use offers no benefit while increasing susceptibility to infection and its risks through partial immunosuppression.

“Considering these contradictory effects of inhaled corticosteroid use, further research is needed regarding its risks and benefits in asthma patients with bronchiectasis, including differences in the benefit of inhaled corticosteroid use according to patient phenotype,” Dr. Kim and his colleagues concluded.
 

The role of corticosteroids

“One of the more important points discussed in this observational cohort study is the role of inhaled corticosteroid use in bronchiectasis,” said Mary Jo Farmer, MD, PhD, director of pulmonary hypertension services, Baystate Health, and assistant professor of medicine, University of Massachusetts – Baystate, both in Springfield, in an interview with this news organization. She cited a review finding no significant benefit versus placebo in spirometry, exacerbation rate, or sputum volume in the Cochrane Database of Systematic Reviews and another suggesting that quality of life was improved with inhaled corticosteroid use in individuals with blood eosinophils greater than 3%, compared with those not using inhaled corticosteroids or having lower eosinophil counts in the European Respiratory Journal. She cited also higher percentages (48% versus 23%) of adrenal insufficiency in bronchiectasis patients among those taking inhaled corticosteroids versus those not taking them.

Dr. Farmer added, “According to the 2018 Cochrane review of inhaled corticosteroid treatment for non–cystic fibrosis bronchiectasis, results from most randomized, placebo-controlled trials have been disappointing in terms of effects on most endpoints such as pulmonary function and exacerbation frequency. As such, the European Respiratory Society guidelines for the management of adult bronchiectasis advise against prescribing inhaled corticosteroids to patients with bronchiectasis, unless otherwise indicated by either an asthma or chronic obstructive pulmonary disease diagnosis. Also, inhaled corticosteroid treatment in asthma and COPD is associated with common side effects such as oral candidiasis, dysphonia and, in some cases, systemic corticosteroid effects. The rate of adverse events from inhaled corticosteroid treatment of bronchiectasis, however, is largely unknown.Dr. Lee and Dr. Farmer reported no relevant financial relationships. The study was independently supported.

When asthma patients are having frequent clinical deteriorations, clinicians need to evaluate them for the presence and severity of bronchiectasis, according to the authors of a retrospective study in the Journal of Allergy and Clinical Immunology: In Practice. While bronchiectasis is known to worsen the clinical and functional outcomes in patients with asthma, data regarding the long-term effects of bronchiectasis on the clinical course of asthma have been limited, stated corresponding author Jung-Kyu Lee, MD, division of pulmonary and critical care medicine, Seoul (Republic of Korea) Metropolitan Government – Seoul National University.

Moderate to severe acute clinical deterioration risks were increased among the 251 patients (mean age 66.6 years, 77.2% men) with bronchiectasis out of 667 asthma patients included in the study. All studied patients underwent chest computed tomography and pulmonary function tests from 2013 to 2019 at two tertiary hospitals in Seoul. The primary outcome, annual incidence of moderate to severe acute exacerbations requiring additional treatment (systemic steroids, antibiotics, or both), was significantly higher in patients with bronchiectasis after a mean follow-up period of 3.96 years. Compared with patients who did not exhibit bronchiectasis, the annual rates of severe exacerbations (0.15 ± 0.43 vs. 0.08 ± 0.27; P = .010), moderate to severe (0.47 ± 0.79 vs. 0.34 ± 0.63; P = .018), and acute exacerbations during the follow-up period (49.8% vs. 39.4%; P = .009) were all significantly higher. There was no difference in the proportion of frequent exacerbators between the two groups, however. Severe acute exacerbations leading to hospitalizations, also, were more frequent in the group with bronchiectasis.
 

Risk factors explored

Significant factors conferring greater risk of severe and moderate to severe acute exacerbations in multivariable analysis included low body mass index, low baseline forced expiratory volume in 1 second (FEV₁), high use of inhaled corticosteroids, high medication possession, and high neutrophil/lymphocyte ratios. The existence of bronchiectasis remained an independent risk factor for severe and moderate to severe acute exacerbations despite adjustment for all other factors. While bronchiectasis score showed no association with annual rate of acute exacerbation, progression of bronchiectasis confirmed on follow-up CT was associated with increased risks of severe and moderate to severe acute exacerbation.

Included patients had a diagnosis of asthma confirmed by variable expiratory airflow limitation with pulmonary function tests (that is, positive bronchodilator response, positive bronchial provocation test, or excessive variation in lung function between visits). Past histories of tuberculosis and nontuberculous mycobacterial lung disease, lower absolute and predicted values of both baseline FEV₁ and forced vital capacity were more common among patients with bronchiectasis.

Dividing the study population into a group that had at least one moderate to severe acute exacerbation during the follow-up period and a group that did not, the researchers identified characteristics shared by exacerbators: a greater proportion were women, they had lower forced vital capacity and lung-diffusing capacity for carbon monoxide, higher blood FVC and blood neutrophil/lymphocyte ratio, and more medication use (inhaled corticosteroids, long-acting antimuscarinic agent, leukotriene-receptor antagonist, and methylxanthine), compared with the nonexacerbators. More bronchiectasis, more severe bronchiectasis (higher bronchiectasis score), and more progression of bronchiectasis were common among the exacerbators.

Higher acute exacerbation risks accompanied bronchiectasis, at 1.47-fold for moderate, 1.72-fold for severe, and 1.50-fold for moderate to severe exacerbations. Higher risk for severe and moderate to severe exacerbations was conferred by bronchiectasis progression, also.

The researchers pointed to contradictory effects of inhaled corticosteroid use, noting both corticosteroids’ essential role in controlling airway inflammation and hyperresponsiveness, exacerbations, and lung-function decline in asthma patients and that longer or greater inhaled corticosteroid use is associated with both clinical deterioration in asthma and bronchiectasis, and exacerbation history. For bronchiectasis, however, inhaled corticosteroid use offers no benefit while increasing susceptibility to infection and its risks through partial immunosuppression.

“Considering these contradictory effects of inhaled corticosteroid use, further research is needed regarding its risks and benefits in asthma patients with bronchiectasis, including differences in the benefit of inhaled corticosteroid use according to patient phenotype,” Dr. Kim and his colleagues concluded.
 

The role of corticosteroids

“One of the more important points discussed in this observational cohort study is the role of inhaled corticosteroid use in bronchiectasis,” said Mary Jo Farmer, MD, PhD, director of pulmonary hypertension services, Baystate Health, and assistant professor of medicine, University of Massachusetts – Baystate, both in Springfield, in an interview with this news organization. She cited a review finding no significant benefit versus placebo in spirometry, exacerbation rate, or sputum volume in the Cochrane Database of Systematic Reviews and another suggesting that quality of life was improved with inhaled corticosteroid use in individuals with blood eosinophils greater than 3%, compared with those not using inhaled corticosteroids or having lower eosinophil counts in the European Respiratory Journal. She cited also higher percentages (48% versus 23%) of adrenal insufficiency in bronchiectasis patients among those taking inhaled corticosteroids versus those not taking them.

Dr. Farmer added, “According to the 2018 Cochrane review of inhaled corticosteroid treatment for non–cystic fibrosis bronchiectasis, results from most randomized, placebo-controlled trials have been disappointing in terms of effects on most endpoints such as pulmonary function and exacerbation frequency. As such, the European Respiratory Society guidelines for the management of adult bronchiectasis advise against prescribing inhaled corticosteroids to patients with bronchiectasis, unless otherwise indicated by either an asthma or chronic obstructive pulmonary disease diagnosis. Also, inhaled corticosteroid treatment in asthma and COPD is associated with common side effects such as oral candidiasis, dysphonia and, in some cases, systemic corticosteroid effects. The rate of adverse events from inhaled corticosteroid treatment of bronchiectasis, however, is largely unknown.Dr. Lee and Dr. Farmer reported no relevant financial relationships. The study was independently supported.

Acute exacerbations (AEs) are both common in rheumatoid arthritis–associated interstitial lung disease (RA-ILD) and are a frequent cause of imminent mortality, a retrospective Japanese study suggests.

The same is also true for patients with idiopathic pulmonary fibrosis (IPF) for whom an AE is the most frequent cause of death as well, the same comparative study indicates.

“Several studies have reported that acute exacerbation, which occurs during the clinical course of idiopathic pulmonary fibrosis (IPF), also occurs in rheumatoid arthritis–associated interstitial lung disease (RA-ILD),” lead author Junji Otsuka, MD, PhD, of the National Hospital Organization Omuta National Hospital, Fukuoka, Japan, and colleagues observed.

“[We found that] AE was not uncommon in RA-ILD or IPF ... but the prognosis after AE of RA-ILD was significantly better than that of IPF [even though] the most frequent cause of death in RA-ILD and IPF was AE,” they stated.

The study was published online in Respiratory Medicine.

Patient features

The study involved 149 RA-ILD patients with a median age of 72 years at RA onset. The median time from ILD diagnosis to onset of AE was 48.5 months, while the median survival time after the onset of AE was 196 days (range 1-3,463 days), as the authors detailed. “All patients were treated with corticosteroids,” the authors noted, and almost all of them were treated with steroid pulse therapy.

Noninvasive positive pressure ventilation (NPPV) was used to maintain oxygenation in 18.5% of patients with severe respiratory failure, while invasive positive pressure ventilation (IPPV) was used in almost 26% of patients with the same degree of respiratory failure. Features of patients who developed an AE were then compared with those who did not.

Interestingly, no significant differences in clinical parameters were seen between those who developed an AE and those who did not. Nor were there any significant differences between the 2 groups in the length of time from the ILD diagnosis to the development of an AE. Some 18% of RA-ILD patients developed an AE, as did over 27% of patients with IPF, investigators report.

The median survival after RA-ILD patients developed an AE was 277 days, compared with only 60 days for those with IPF (P = .038). In a multivariable analysis, hypoalbuminemia at an odds ratio of .090 (95% confidence interval, 0.011-0.733; P = .012) as well as percent carbon monoxide diffusion capacity at an OR of .810 (95% CI, 0.814-0.964; P < .01) were both independent risk factors for the development of an AE, the investigators pointed out.

The best cut-off level for predicting the risk of an AE was 3.0 g/dL (95% CI, 0.011-0.733; P = .012) for serum albumin and 53% (95% CI, 0.814-0.964; P < .01) for carbon monoxide diffusion capacity. As Dr. Otsuka noted in an email to this news organization, low serum albumin likely correlates with a generally poor condition, while low carbon monoxide diffusion capacity is likely due to lung fibrosis.

“But if low albumin and low carbon monoxide diffusion capacity are due to the progression of ILD, both values may be difficult to improve,” he added.
 

Survivors versus nonsurvivors

Of those patients with RA-ILD who developed an AE, approximately half recovered. Among the IPF patients who developed an AE during the study period, approximately 39% recovered from the event, while 70% did not. Comparing RA-ILD patients who survived versus whose who did not, again, no significant demographic or clinical differences were seen between the 2 groups. On the other hand, the number of patients treated with immunosuppressants for their AE was significantly higher among patients who did not survive the AE, compared with those who did (P =.022), investigators note.

Similarly, the number of patients who required NPPV was also significantly higher among those who did not survive, compared with those who did. In fact, “none of the surviving patients used NPPV (P <0.01),” the authors stress. The number of patients who required IPPV was also significantly higher among nonsurvivors than among survivors (P =.017), and of the small number of patients who were treated with IPPV, all but one died without recovery.

As the authors suggested, these findings suggest that RA-ILD patients who recover from an AE with the help of corticosteroids alone have a relatively decent prognosis. In contrast, those who require immunosuppressive drugs in addition to steroids or mechanical ventilation for AE management can be expected to have a poor prognosis.

The same can also be said for IPF patients and even with the help of mechanical ventilation “with IPF patients, the survival rate is low anyway, so the indication for mechanical ventilation should be carefully judged,” Dr. Otsuka stressed.
 

Cause of death

The authors also compared the cause of death between patients with RA-ILD and those with IPF. “In RA-ILD patients, the most frequent cause of death was AE,” they report, at close to 35% of all patients with RA-ILD. This was also true for IPF patients among whom AE was the cause of death for over 44%. “These results indicate that, as in IPF, AE develops in the clinical course of RA-ILD with considerable frequency,” investigators note.

“During the clinical course of RA-ILD, as with IPD, it is necessary to pay attention to AE,” they stress. Dr. Otsuka added: “It may be difficult to change the prognosis of these patients.”

“However, knowing which patients are more likely to develop AE may help predict the prognosis, and it may be improved if antifibrotic agents are used for these patients,” he said. Elizabeth Volkmann, MD, director, UCLA scleroderma program, University of California, Los Angeles, felt that understanding the risk factors for AEs in this patient population may help physicians identify a subgroup of patients with RA-ILD who require closer monitoring and follow-up.

“These patients may also require more aggressive treatment for RA-ILD to prevent AEs,” she said in an email to this news organization. Given that the study was retrospective in nature, Dr. Volkmann cautioned that there were likely multiple confounding factors that could have affected survival in this patient population and not to take away from the study that survival was solely affected by immunosuppressant use, for example.

“It is possible that patients [treated with] immunosuppressants had other features of their disease that independently heightened their risk of mortality,” Dr. Volkmann said. Similarly, physicians should not assume that the high mortality rate seen in RA-ILD patients who were treated with mechanical ventilation had anything to do with mechanical ventilation itself, as patients requiring ventilation are likely to have worse outcomes, as she stressed.

As for hypoalbuminemia, Dr. Volkmann pointed out that hypoalbuminemia is often a sign of malnutrition in these patients. “Studies have demonstrated that malnutrition is an independent predictor of mortality in patients with ILD,” she emphasized.

“Optimizing patients’ nutritional status could potentially help lower the risk of AEs,” Dr. Volkmann suggested.

Limitations of the study include the fact that it was a single-center design study and included only a limited number of patients.

No specific funding source was noted. The authors have no conflicts of interest to declare.

Acute exacerbations (AEs) are both common in rheumatoid arthritis–associated interstitial lung disease (RA-ILD) and are a frequent cause of imminent mortality, a retrospective Japanese study suggests.

The same is also true for patients with idiopathic pulmonary fibrosis (IPF) for whom an AE is the most frequent cause of death as well, the same comparative study indicates.

“Several studies have reported that acute exacerbation, which occurs during the clinical course of idiopathic pulmonary fibrosis (IPF), also occurs in rheumatoid arthritis–associated interstitial lung disease (RA-ILD),” lead author Junji Otsuka, MD, PhD, of the National Hospital Organization Omuta National Hospital, Fukuoka, Japan, and colleagues observed.

“[We found that] AE was not uncommon in RA-ILD or IPF ... but the prognosis after AE of RA-ILD was significantly better than that of IPF [even though] the most frequent cause of death in RA-ILD and IPF was AE,” they stated.

The study was published online in Respiratory Medicine.

Patient features

The study involved 149 RA-ILD patients with a median age of 72 years at RA onset. The median time from ILD diagnosis to onset of AE was 48.5 months, while the median survival time after the onset of AE was 196 days (range 1-3,463 days), as the authors detailed. “All patients were treated with corticosteroids,” the authors noted, and almost all of them were treated with steroid pulse therapy.

Noninvasive positive pressure ventilation (NPPV) was used to maintain oxygenation in 18.5% of patients with severe respiratory failure, while invasive positive pressure ventilation (IPPV) was used in almost 26% of patients with the same degree of respiratory failure. Features of patients who developed an AE were then compared with those who did not.

Interestingly, no significant differences in clinical parameters were seen between those who developed an AE and those who did not. Nor were there any significant differences between the 2 groups in the length of time from the ILD diagnosis to the development of an AE. Some 18% of RA-ILD patients developed an AE, as did over 27% of patients with IPF, investigators report.

The median survival after RA-ILD patients developed an AE was 277 days, compared with only 60 days for those with IPF (P = .038). In a multivariable analysis, hypoalbuminemia at an odds ratio of .090 (95% confidence interval, 0.011-0.733; P = .012) as well as percent carbon monoxide diffusion capacity at an OR of .810 (95% CI, 0.814-0.964; P < .01) were both independent risk factors for the development of an AE, the investigators pointed out.

The best cut-off level for predicting the risk of an AE was 3.0 g/dL (95% CI, 0.011-0.733; P = .012) for serum albumin and 53% (95% CI, 0.814-0.964; P < .01) for carbon monoxide diffusion capacity. As Dr. Otsuka noted in an email to this news organization, low serum albumin likely correlates with a generally poor condition, while low carbon monoxide diffusion capacity is likely due to lung fibrosis.

“But if low albumin and low carbon monoxide diffusion capacity are due to the progression of ILD, both values may be difficult to improve,” he added.
 

Survivors versus nonsurvivors

Of those patients with RA-ILD who developed an AE, approximately half recovered. Among the IPF patients who developed an AE during the study period, approximately 39% recovered from the event, while 70% did not. Comparing RA-ILD patients who survived versus whose who did not, again, no significant demographic or clinical differences were seen between the 2 groups. On the other hand, the number of patients treated with immunosuppressants for their AE was significantly higher among patients who did not survive the AE, compared with those who did (P =.022), investigators note.

Similarly, the number of patients who required NPPV was also significantly higher among those who did not survive, compared with those who did. In fact, “none of the surviving patients used NPPV (P <0.01),” the authors stress. The number of patients who required IPPV was also significantly higher among nonsurvivors than among survivors (P =.017), and of the small number of patients who were treated with IPPV, all but one died without recovery.

As the authors suggested, these findings suggest that RA-ILD patients who recover from an AE with the help of corticosteroids alone have a relatively decent prognosis. In contrast, those who require immunosuppressive drugs in addition to steroids or mechanical ventilation for AE management can be expected to have a poor prognosis.

The same can also be said for IPF patients and even with the help of mechanical ventilation “with IPF patients, the survival rate is low anyway, so the indication for mechanical ventilation should be carefully judged,” Dr. Otsuka stressed.
 

Cause of death

The authors also compared the cause of death between patients with RA-ILD and those with IPF. “In RA-ILD patients, the most frequent cause of death was AE,” they report, at close to 35% of all patients with RA-ILD. This was also true for IPF patients among whom AE was the cause of death for over 44%. “These results indicate that, as in IPF, AE develops in the clinical course of RA-ILD with considerable frequency,” investigators note.

“During the clinical course of RA-ILD, as with IPD, it is necessary to pay attention to AE,” they stress. Dr. Otsuka added: “It may be difficult to change the prognosis of these patients.”

“However, knowing which patients are more likely to develop AE may help predict the prognosis, and it may be improved if antifibrotic agents are used for these patients,” he said. Elizabeth Volkmann, MD, director, UCLA scleroderma program, University of California, Los Angeles, felt that understanding the risk factors for AEs in this patient population may help physicians identify a subgroup of patients with RA-ILD who require closer monitoring and follow-up.

“These patients may also require more aggressive treatment for RA-ILD to prevent AEs,” she said in an email to this news organization. Given that the study was retrospective in nature, Dr. Volkmann cautioned that there were likely multiple confounding factors that could have affected survival in this patient population and not to take away from the study that survival was solely affected by immunosuppressant use, for example.

“It is possible that patients [treated with] immunosuppressants had other features of their disease that independently heightened their risk of mortality,” Dr. Volkmann said. Similarly, physicians should not assume that the high mortality rate seen in RA-ILD patients who were treated with mechanical ventilation had anything to do with mechanical ventilation itself, as patients requiring ventilation are likely to have worse outcomes, as she stressed.

As for hypoalbuminemia, Dr. Volkmann pointed out that hypoalbuminemia is often a sign of malnutrition in these patients. “Studies have demonstrated that malnutrition is an independent predictor of mortality in patients with ILD,” she emphasized.

“Optimizing patients’ nutritional status could potentially help lower the risk of AEs,” Dr. Volkmann suggested.

Limitations of the study include the fact that it was a single-center design study and included only a limited number of patients.

No specific funding source was noted. The authors have no conflicts of interest to declare.

Acute exacerbations (AEs) are both common in rheumatoid arthritis–associated interstitial lung disease (RA-ILD) and are a frequent cause of imminent mortality, a retrospective Japanese study suggests.

The same is also true for patients with idiopathic pulmonary fibrosis (IPF) for whom an AE is the most frequent cause of death as well, the same comparative study indicates.

“Several studies have reported that acute exacerbation, which occurs during the clinical course of idiopathic pulmonary fibrosis (IPF), also occurs in rheumatoid arthritis–associated interstitial lung disease (RA-ILD),” lead author Junji Otsuka, MD, PhD, of the National Hospital Organization Omuta National Hospital, Fukuoka, Japan, and colleagues observed.

“[We found that] AE was not uncommon in RA-ILD or IPF ... but the prognosis after AE of RA-ILD was significantly better than that of IPF [even though] the most frequent cause of death in RA-ILD and IPF was AE,” they stated.

The study was published online in Respiratory Medicine.

Patient features

The study involved 149 RA-ILD patients with a median age of 72 years at RA onset. The median time from ILD diagnosis to onset of AE was 48.5 months, while the median survival time after the onset of AE was 196 days (range 1-3,463 days), as the authors detailed. “All patients were treated with corticosteroids,” the authors noted, and almost all of them were treated with steroid pulse therapy.

Noninvasive positive pressure ventilation (NPPV) was used to maintain oxygenation in 18.5% of patients with severe respiratory failure, while invasive positive pressure ventilation (IPPV) was used in almost 26% of patients with the same degree of respiratory failure. Features of patients who developed an AE were then compared with those who did not.

Interestingly, no significant differences in clinical parameters were seen between those who developed an AE and those who did not. Nor were there any significant differences between the 2 groups in the length of time from the ILD diagnosis to the development of an AE. Some 18% of RA-ILD patients developed an AE, as did over 27% of patients with IPF, investigators report.

The median survival after RA-ILD patients developed an AE was 277 days, compared with only 60 days for those with IPF (P = .038). In a multivariable analysis, hypoalbuminemia at an odds ratio of .090 (95% confidence interval, 0.011-0.733; P = .012) as well as percent carbon monoxide diffusion capacity at an OR of .810 (95% CI, 0.814-0.964; P < .01) were both independent risk factors for the development of an AE, the investigators pointed out.

The best cut-off level for predicting the risk of an AE was 3.0 g/dL (95% CI, 0.011-0.733; P = .012) for serum albumin and 53% (95% CI, 0.814-0.964; P < .01) for carbon monoxide diffusion capacity. As Dr. Otsuka noted in an email to this news organization, low serum albumin likely correlates with a generally poor condition, while low carbon monoxide diffusion capacity is likely due to lung fibrosis.

“But if low albumin and low carbon monoxide diffusion capacity are due to the progression of ILD, both values may be difficult to improve,” he added.
 

Survivors versus nonsurvivors

Of those patients with RA-ILD who developed an AE, approximately half recovered. Among the IPF patients who developed an AE during the study period, approximately 39% recovered from the event, while 70% did not. Comparing RA-ILD patients who survived versus whose who did not, again, no significant demographic or clinical differences were seen between the 2 groups. On the other hand, the number of patients treated with immunosuppressants for their AE was significantly higher among patients who did not survive the AE, compared with those who did (P =.022), investigators note.

Similarly, the number of patients who required NPPV was also significantly higher among those who did not survive, compared with those who did. In fact, “none of the surviving patients used NPPV (P <0.01),” the authors stress. The number of patients who required IPPV was also significantly higher among nonsurvivors than among survivors (P =.017), and of the small number of patients who were treated with IPPV, all but one died without recovery.

As the authors suggested, these findings suggest that RA-ILD patients who recover from an AE with the help of corticosteroids alone have a relatively decent prognosis. In contrast, those who require immunosuppressive drugs in addition to steroids or mechanical ventilation for AE management can be expected to have a poor prognosis.

The same can also be said for IPF patients and even with the help of mechanical ventilation “with IPF patients, the survival rate is low anyway, so the indication for mechanical ventilation should be carefully judged,” Dr. Otsuka stressed.
 

Cause of death

The authors also compared the cause of death between patients with RA-ILD and those with IPF. “In RA-ILD patients, the most frequent cause of death was AE,” they report, at close to 35% of all patients with RA-ILD. This was also true for IPF patients among whom AE was the cause of death for over 44%. “These results indicate that, as in IPF, AE develops in the clinical course of RA-ILD with considerable frequency,” investigators note.

“During the clinical course of RA-ILD, as with IPD, it is necessary to pay attention to AE,” they stress. Dr. Otsuka added: “It may be difficult to change the prognosis of these patients.”

“However, knowing which patients are more likely to develop AE may help predict the prognosis, and it may be improved if antifibrotic agents are used for these patients,” he said. Elizabeth Volkmann, MD, director, UCLA scleroderma program, University of California, Los Angeles, felt that understanding the risk factors for AEs in this patient population may help physicians identify a subgroup of patients with RA-ILD who require closer monitoring and follow-up.

“These patients may also require more aggressive treatment for RA-ILD to prevent AEs,” she said in an email to this news organization. Given that the study was retrospective in nature, Dr. Volkmann cautioned that there were likely multiple confounding factors that could have affected survival in this patient population and not to take away from the study that survival was solely affected by immunosuppressant use, for example.

“It is possible that patients [treated with] immunosuppressants had other features of their disease that independently heightened their risk of mortality,” Dr. Volkmann said. Similarly, physicians should not assume that the high mortality rate seen in RA-ILD patients who were treated with mechanical ventilation had anything to do with mechanical ventilation itself, as patients requiring ventilation are likely to have worse outcomes, as she stressed.

As for hypoalbuminemia, Dr. Volkmann pointed out that hypoalbuminemia is often a sign of malnutrition in these patients. “Studies have demonstrated that malnutrition is an independent predictor of mortality in patients with ILD,” she emphasized.

“Optimizing patients’ nutritional status could potentially help lower the risk of AEs,” Dr. Volkmann suggested.

Limitations of the study include the fact that it was a single-center design study and included only a limited number of patients.

No specific funding source was noted. The authors have no conflicts of interest to declare.

Cannabis users had a 22% increased risk of an emergency department (ED) visit or hospitalization compared to nonusers, as determined from data from more than 30,000 individuals.

Although cannabis contains compounds similar to tobacco, “data published on the association between cannabis smoking and airways health have been contradictory,” and whether smoking cannabis increases a user’s risk of developing acute respiratory illness remains unclear, wrote Nicholas T. Vozoris, MD, of the University of Toronto, and colleagues.

Smithore/Getty Images

In a study published in BMJ Open Respiratory Research, the investigators reviewed national health records data from 35,114 individuals aged 12-65 years for the period January 2009 to December 2015. Of these persons, 4,807 of the 6,425 who reported cannabis use in the past year were matched with 10,395 never-users who served as controls. The mean age of the study population at the index date was 35 years, and 42% were women; demographics were similar between users and control persons.

Overall, the odds of respiratory-related emergency department visits or hospitalizations were not significantly different between the cannabis users and the control persons (3.6% vs. 3.9%; odds ratio, 0.91). However, cannabis users had significantly greater odds of all-cause ED visits or hospitalizations (30.0% vs. 26.0%; OR, 1.22). All-cause mortality was 0.2% for both groups.

Respiratory problems were the second-highest reason for all-cause visits, the researchers noted. The lack of a difference in respiratory-related visits between cannabis users and nonusers conflicts somewhat with previous studies on this topic, which were limited, the researchers noted in their discussion.

The negative results also might stem from factors for which the researchers could not adjust, including insufficient cannabis smoke exposure among users in the study population, noninhalational cannabis use, which is less likely to have a respiratory effect, and possible secondhand exposure among control persons.

“It is also possible that our analysis might have been insufficiently powered to detect a significant signal with respect to the primary outcome,” they noted.

However, after the researchers controlled for multiple variables, the risk of an equally important morbidity outcome, all-cause ED visits or hospitalizations, was significantly greater among cannabis users than among control individuals, and respiratory reasons were the second most common cause for ED visits and hospitalizations in the all-cause outcome, they emphasized.

The study findings were limited by several factors, including the retrospective and observational design and the inability to control for all confounding variables, the researchers noted. Other limitations include the use of self-reports and potential for bias, the inability to perform dose-response analysis, and the high number of infrequent cannabis users in the study population.

However, the results suggest that cannabis use is associated with an increased risk of serious health events and should be discouraged, although more research is needed to confirm the current study findings, they concluded.
 

Consider range of causes for cannabis emergency visits

“With growing numbers of states legalizing recreational use of cannabis, it’s important to understand whether cannabis use is associated with increased emergency department visits,” Robert D. Glatter, MD, an emergency medicine physician at Lenox Hill Hospital, New York, told this news organization.

Previous studies have shown an association between increased ED visits and cannabis use in states, especially with edibles, where cannabis is legal, and “the current study reinforces the elevated risk of ED visits along with hospitalizations,” he said.

“While the researchers found no increased risk of respiratory-related complaints among users compared to the general population, there was an associated increase in ED visits and hospitalizations, which is important to understand,” said Dr. Glatter, who was not involved in the study.

“While this observational study found that the incidence of respiratory complaints was not significantly different among frequent users of cannabis, the increased odds that cannabis users would require evaluation in the emergency room or even hospitalization was still apparent even after the investigators controlled for such factors as use of alcohol, tobacco, illicit drug use, or other mental health–related disorders,” Dr. Glatter noted.

“That said, it’s a bit surprising that with the continued popularity of vaping, especially among teens, there was still not any appreciable or significant increase in respiratory complaints observed. Beyond this finding, I was not surprised by the overall conclusions of the current study, as we continue to see an elevated number of patients presenting to the ED with adverse events related to cannabis use.”

Dr. Glatter noted that “the majority of patients we see in the ED are associated with use of edibles, since it takes longer for the person to feel the effects, leading the user to consume more of the product up front, with delayed effects lasting up to 12 hours. This is what gets people into trouble and leads to toxicity of cannabis, or ‘overdoses,’ “ he explained.

When consuming edible cannabis products, “[p]eople need to begin at low dosages and not take additional gummies up front, since it can take up to 2 or even 3 hours in some cases to feel the initial effects. With the drug’s effects lasting up to 12 hours, it’s especially important to avoid operating any motor vehicles, bicycles, or scooters, since reaction time is impaired, as well as overall judgment, balance, and fine motor skills,” Dr. Glatter said.

Cannabis can land users in the ED for a range of reasons, said Dr. Glatter. “According to the study, 15% of the emergency room visits and hospitalizations were due to acute trauma, 14% due to respiratory issues, and 13% to gastrointestinal illnesses. These effects were seen in first-time users but not those with chronic use, according to the study inclusion criteria.”

Cannabis use could result in physical injuries through “impaired judgment, coordination, combined with an altered state of consciousness or generalized drowsiness, that could contribute to an increase in motor vehicle collisions, along with an increased risk for falls leading to lacerations, fractures, contusions, or bruising,” said Dr. Glatter. “Cannabis may also lead to an altered sense of perception related to interactions with others, resulting in feelings of anxiety or restlessness culminating in physical altercations and other injuries.”

The current study indicates the need for understanding the potential physical and psychological effects of cannabis use, he said.

“Additional research is needed to better understand the relative percentage cases related to edibles vs. inhalation presenting to the ED,” he noted. “There is no question that edibles continue to present significant dangers for those who don’t read labels or remain poorly informed regarding their dosing as a result of delayed onset and longer duration,” he said. To help reduce risk of toxicity, the concept of a “high lasting 12-15 hours, as with edibles, as opposed to 3-4 hours from inhalation must be clearly stated on packaging and better communicated with users, as the toxicity with edibles is more often from lack of prior knowledge about onset of effects related to dosing.”

In addition, the “potential for psychosis to develop with more chronic cannabis use, along with cannabinoid hyperemesis syndrome should be on every clinician’s radar,” Dr. Glatter emphasized.

“The bottom line is that as more states legalize the use of cannabis, it’s vital to also implement comprehensive public education efforts to provide users with the reported risks associated with not only inhalation (vaping or flower) but also edibles, which account for an increasingly greater percentage of ED visits and associated adverse effects,” he said.

The study was supported by the Lung Association–Ontario, as well as by grants from the Ontario Ministry of Health and the Ministry of Long-Term Care. The researchers and Dr. Glatter have disclosed no relevant financial relationships.

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

Cannabis users had a 22% increased risk of an emergency department (ED) visit or hospitalization compared to nonusers, as determined from data from more than 30,000 individuals.

Although cannabis contains compounds similar to tobacco, “data published on the association between cannabis smoking and airways health have been contradictory,” and whether smoking cannabis increases a user’s risk of developing acute respiratory illness remains unclear, wrote Nicholas T. Vozoris, MD, of the University of Toronto, and colleagues.

Smithore/Getty Images

In a study published in BMJ Open Respiratory Research, the investigators reviewed national health records data from 35,114 individuals aged 12-65 years for the period January 2009 to December 2015. Of these persons, 4,807 of the 6,425 who reported cannabis use in the past year were matched with 10,395 never-users who served as controls. The mean age of the study population at the index date was 35 years, and 42% were women; demographics were similar between users and control persons.

Overall, the odds of respiratory-related emergency department visits or hospitalizations were not significantly different between the cannabis users and the control persons (3.6% vs. 3.9%; odds ratio, 0.91). However, cannabis users had significantly greater odds of all-cause ED visits or hospitalizations (30.0% vs. 26.0%; OR, 1.22). All-cause mortality was 0.2% for both groups.

Respiratory problems were the second-highest reason for all-cause visits, the researchers noted. The lack of a difference in respiratory-related visits between cannabis users and nonusers conflicts somewhat with previous studies on this topic, which were limited, the researchers noted in their discussion.

The negative results also might stem from factors for which the researchers could not adjust, including insufficient cannabis smoke exposure among users in the study population, noninhalational cannabis use, which is less likely to have a respiratory effect, and possible secondhand exposure among control persons.

“It is also possible that our analysis might have been insufficiently powered to detect a significant signal with respect to the primary outcome,” they noted.

However, after the researchers controlled for multiple variables, the risk of an equally important morbidity outcome, all-cause ED visits or hospitalizations, was significantly greater among cannabis users than among control individuals, and respiratory reasons were the second most common cause for ED visits and hospitalizations in the all-cause outcome, they emphasized.

The study findings were limited by several factors, including the retrospective and observational design and the inability to control for all confounding variables, the researchers noted. Other limitations include the use of self-reports and potential for bias, the inability to perform dose-response analysis, and the high number of infrequent cannabis users in the study population.

However, the results suggest that cannabis use is associated with an increased risk of serious health events and should be discouraged, although more research is needed to confirm the current study findings, they concluded.
 

Consider range of causes for cannabis emergency visits

“With growing numbers of states legalizing recreational use of cannabis, it’s important to understand whether cannabis use is associated with increased emergency department visits,” Robert D. Glatter, MD, an emergency medicine physician at Lenox Hill Hospital, New York, told this news organization.

Previous studies have shown an association between increased ED visits and cannabis use in states, especially with edibles, where cannabis is legal, and “the current study reinforces the elevated risk of ED visits along with hospitalizations,” he said.

“While the researchers found no increased risk of respiratory-related complaints among users compared to the general population, there was an associated increase in ED visits and hospitalizations, which is important to understand,” said Dr. Glatter, who was not involved in the study.

“While this observational study found that the incidence of respiratory complaints was not significantly different among frequent users of cannabis, the increased odds that cannabis users would require evaluation in the emergency room or even hospitalization was still apparent even after the investigators controlled for such factors as use of alcohol, tobacco, illicit drug use, or other mental health–related disorders,” Dr. Glatter noted.

“That said, it’s a bit surprising that with the continued popularity of vaping, especially among teens, there was still not any appreciable or significant increase in respiratory complaints observed. Beyond this finding, I was not surprised by the overall conclusions of the current study, as we continue to see an elevated number of patients presenting to the ED with adverse events related to cannabis use.”

Dr. Glatter noted that “the majority of patients we see in the ED are associated with use of edibles, since it takes longer for the person to feel the effects, leading the user to consume more of the product up front, with delayed effects lasting up to 12 hours. This is what gets people into trouble and leads to toxicity of cannabis, or ‘overdoses,’ “ he explained.

When consuming edible cannabis products, “[p]eople need to begin at low dosages and not take additional gummies up front, since it can take up to 2 or even 3 hours in some cases to feel the initial effects. With the drug’s effects lasting up to 12 hours, it’s especially important to avoid operating any motor vehicles, bicycles, or scooters, since reaction time is impaired, as well as overall judgment, balance, and fine motor skills,” Dr. Glatter said.

Cannabis can land users in the ED for a range of reasons, said Dr. Glatter. “According to the study, 15% of the emergency room visits and hospitalizations were due to acute trauma, 14% due to respiratory issues, and 13% to gastrointestinal illnesses. These effects were seen in first-time users but not those with chronic use, according to the study inclusion criteria.”

Cannabis use could result in physical injuries through “impaired judgment, coordination, combined with an altered state of consciousness or generalized drowsiness, that could contribute to an increase in motor vehicle collisions, along with an increased risk for falls leading to lacerations, fractures, contusions, or bruising,” said Dr. Glatter. “Cannabis may also lead to an altered sense of perception related to interactions with others, resulting in feelings of anxiety or restlessness culminating in physical altercations and other injuries.”

The current study indicates the need for understanding the potential physical and psychological effects of cannabis use, he said.

“Additional research is needed to better understand the relative percentage cases related to edibles vs. inhalation presenting to the ED,” he noted. “There is no question that edibles continue to present significant dangers for those who don’t read labels or remain poorly informed regarding their dosing as a result of delayed onset and longer duration,” he said. To help reduce risk of toxicity, the concept of a “high lasting 12-15 hours, as with edibles, as opposed to 3-4 hours from inhalation must be clearly stated on packaging and better communicated with users, as the toxicity with edibles is more often from lack of prior knowledge about onset of effects related to dosing.”

In addition, the “potential for psychosis to develop with more chronic cannabis use, along with cannabinoid hyperemesis syndrome should be on every clinician’s radar,” Dr. Glatter emphasized.

“The bottom line is that as more states legalize the use of cannabis, it’s vital to also implement comprehensive public education efforts to provide users with the reported risks associated with not only inhalation (vaping or flower) but also edibles, which account for an increasingly greater percentage of ED visits and associated adverse effects,” he said.

The study was supported by the Lung Association–Ontario, as well as by grants from the Ontario Ministry of Health and the Ministry of Long-Term Care. The researchers and Dr. Glatter have disclosed no relevant financial relationships.

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

Cannabis users had a 22% increased risk of an emergency department (ED) visit or hospitalization compared to nonusers, as determined from data from more than 30,000 individuals.

Although cannabis contains compounds similar to tobacco, “data published on the association between cannabis smoking and airways health have been contradictory,” and whether smoking cannabis increases a user’s risk of developing acute respiratory illness remains unclear, wrote Nicholas T. Vozoris, MD, of the University of Toronto, and colleagues.

Smithore/Getty Images

In a study published in BMJ Open Respiratory Research, the investigators reviewed national health records data from 35,114 individuals aged 12-65 years for the period January 2009 to December 2015. Of these persons, 4,807 of the 6,425 who reported cannabis use in the past year were matched with 10,395 never-users who served as controls. The mean age of the study population at the index date was 35 years, and 42% were women; demographics were similar between users and control persons.

Overall, the odds of respiratory-related emergency department visits or hospitalizations were not significantly different between the cannabis users and the control persons (3.6% vs. 3.9%; odds ratio, 0.91). However, cannabis users had significantly greater odds of all-cause ED visits or hospitalizations (30.0% vs. 26.0%; OR, 1.22). All-cause mortality was 0.2% for both groups.

Respiratory problems were the second-highest reason for all-cause visits, the researchers noted. The lack of a difference in respiratory-related visits between cannabis users and nonusers conflicts somewhat with previous studies on this topic, which were limited, the researchers noted in their discussion.

The negative results also might stem from factors for which the researchers could not adjust, including insufficient cannabis smoke exposure among users in the study population, noninhalational cannabis use, which is less likely to have a respiratory effect, and possible secondhand exposure among control persons.

“It is also possible that our analysis might have been insufficiently powered to detect a significant signal with respect to the primary outcome,” they noted.

However, after the researchers controlled for multiple variables, the risk of an equally important morbidity outcome, all-cause ED visits or hospitalizations, was significantly greater among cannabis users than among control individuals, and respiratory reasons were the second most common cause for ED visits and hospitalizations in the all-cause outcome, they emphasized.

The study findings were limited by several factors, including the retrospective and observational design and the inability to control for all confounding variables, the researchers noted. Other limitations include the use of self-reports and potential for bias, the inability to perform dose-response analysis, and the high number of infrequent cannabis users in the study population.

However, the results suggest that cannabis use is associated with an increased risk of serious health events and should be discouraged, although more research is needed to confirm the current study findings, they concluded.
 

Consider range of causes for cannabis emergency visits

“With growing numbers of states legalizing recreational use of cannabis, it’s important to understand whether cannabis use is associated with increased emergency department visits,” Robert D. Glatter, MD, an emergency medicine physician at Lenox Hill Hospital, New York, told this news organization.

Previous studies have shown an association between increased ED visits and cannabis use in states, especially with edibles, where cannabis is legal, and “the current study reinforces the elevated risk of ED visits along with hospitalizations,” he said.

“While the researchers found no increased risk of respiratory-related complaints among users compared to the general population, there was an associated increase in ED visits and hospitalizations, which is important to understand,” said Dr. Glatter, who was not involved in the study.

“While this observational study found that the incidence of respiratory complaints was not significantly different among frequent users of cannabis, the increased odds that cannabis users would require evaluation in the emergency room or even hospitalization was still apparent even after the investigators controlled for such factors as use of alcohol, tobacco, illicit drug use, or other mental health–related disorders,” Dr. Glatter noted.

“That said, it’s a bit surprising that with the continued popularity of vaping, especially among teens, there was still not any appreciable or significant increase in respiratory complaints observed. Beyond this finding, I was not surprised by the overall conclusions of the current study, as we continue to see an elevated number of patients presenting to the ED with adverse events related to cannabis use.”

Dr. Glatter noted that “the majority of patients we see in the ED are associated with use of edibles, since it takes longer for the person to feel the effects, leading the user to consume more of the product up front, with delayed effects lasting up to 12 hours. This is what gets people into trouble and leads to toxicity of cannabis, or ‘overdoses,’ “ he explained.

When consuming edible cannabis products, “[p]eople need to begin at low dosages and not take additional gummies up front, since it can take up to 2 or even 3 hours in some cases to feel the initial effects. With the drug’s effects lasting up to 12 hours, it’s especially important to avoid operating any motor vehicles, bicycles, or scooters, since reaction time is impaired, as well as overall judgment, balance, and fine motor skills,” Dr. Glatter said.

Cannabis can land users in the ED for a range of reasons, said Dr. Glatter. “According to the study, 15% of the emergency room visits and hospitalizations were due to acute trauma, 14% due to respiratory issues, and 13% to gastrointestinal illnesses. These effects were seen in first-time users but not those with chronic use, according to the study inclusion criteria.”

Cannabis use could result in physical injuries through “impaired judgment, coordination, combined with an altered state of consciousness or generalized drowsiness, that could contribute to an increase in motor vehicle collisions, along with an increased risk for falls leading to lacerations, fractures, contusions, or bruising,” said Dr. Glatter. “Cannabis may also lead to an altered sense of perception related to interactions with others, resulting in feelings of anxiety or restlessness culminating in physical altercations and other injuries.”

The current study indicates the need for understanding the potential physical and psychological effects of cannabis use, he said.

“Additional research is needed to better understand the relative percentage cases related to edibles vs. inhalation presenting to the ED,” he noted. “There is no question that edibles continue to present significant dangers for those who don’t read labels or remain poorly informed regarding their dosing as a result of delayed onset and longer duration,” he said. To help reduce risk of toxicity, the concept of a “high lasting 12-15 hours, as with edibles, as opposed to 3-4 hours from inhalation must be clearly stated on packaging and better communicated with users, as the toxicity with edibles is more often from lack of prior knowledge about onset of effects related to dosing.”

In addition, the “potential for psychosis to develop with more chronic cannabis use, along with cannabinoid hyperemesis syndrome should be on every clinician’s radar,” Dr. Glatter emphasized.

“The bottom line is that as more states legalize the use of cannabis, it’s vital to also implement comprehensive public education efforts to provide users with the reported risks associated with not only inhalation (vaping or flower) but also edibles, which account for an increasingly greater percentage of ED visits and associated adverse effects,” he said.

The study was supported by the Lung Association–Ontario, as well as by grants from the Ontario Ministry of Health and the Ministry of Long-Term Care. The researchers and Dr. Glatter have disclosed no relevant financial relationships.

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

A new study provides more evidence that influenza vaccination may help protect older adults against Alzheimer’s disease (AD).

In a large propensity-matched cohort of older adults, those who had received at least one influenza inoculation were 40% less likely than unvaccinated peers to develop AD over the course of 4 years.

“Influenza infection can cause serious health complications, particularly in adults 65 and older. Our study’s findings – that vaccination against the flu virus may also reduce the risk of Alzheimer’s dementia for at least a few years – adds to the already compelling reasons get the flu vaccine annually,” Avram Bukhbinder, MD, of the University of Texas, Houston, said in an interview.

The new findings support earlier work by the same researchers that also suggested a protective effect of flu vaccination on dementia risk.

The latest study was published online in the Journal of Alzheimer’s Disease.
 

40% lower risk

Prior studies have found a lower risk of dementia of any etiology following influenza vaccination in selected populations, including veterans and patients with serious chronic health conditions.

However, the effect of influenza vaccination on AD risk in a general cohort of older U.S. adults has not been characterized.

Dr. Bukhbinder and colleagues used claims data to create a propensity-matched cohort of 935,887 influenza-vaccinated adults and a like number of unvaccinated adults aged 65 and older.

The median age of the persons in the matched sample was 73.7 years, and 57% were women. All were free of dementia during the 6-year look-back study period.

During median follow-up of 46 months, 47,889 (5.1%) flu-vaccinated adults and 79,630 (8.5%) unvaccinated adults developed AD.

The risk of AD was 40% lower in the vaccinated group (relative risk, 0.60; 95% confidence interval, 0.59-0.61). The absolute risk reduction was 0.034 (95% CI, 0.033-0.035), corresponding to a number needed to treat of 29.4.
 

Mechanism unclear

“Our study does not address the mechanism(s) underlying the apparent effect of influenza vaccination on Alzheimer’s risk, but we look forward to future research investigating this important question,” Dr. Bukhbinder said.

“One possible mechanism is that, by helping to prevent or mitigate infection with the flu virus and the systemic inflammation that follows such an infection, the flu vaccine helps to decrease the systemic inflammation that may have otherwise occurred,” he explained.

It’s also possible that influenza vaccination may trigger non–influenza-specific changes in the immune system that help to reduce the damage caused by AD pathology, including amyloid plaques and neurofibrillary tangles, he said.

“For example, the influenza vaccine may alter the brain’s immune cells such that they are better at clearing Alzheimer’s pathologies, an effect that has been seen in mice, or it may reprogram these immune cells to respond to Alzheimer’s pathologies in ways that are less likely to damage nearby healthy brain cells, or it may do both,” Dr. Bukhbinder noted.
 

Alzheimer’s expert weighs in

Heather M. Snyder, PhD, vice president of medical and scientific relations for the Alzheimer’s Association, said this study “suggests that flu vaccination may be valuable for maintaining cognition and memory as we age. This is even more relevant today in the COVID-19 environment.

“It is too early to tell if getting flu vaccine, on its own, can reduce risk of Alzheimer’s. More research is needed to understand the biological mechanisms behind the results in this study,” Dr. Snyder said in an interview.

“For example, it is possible that people who are getting vaccinated also take better care of their health in other ways, and these things add up to lower risk of Alzheimer’s and other dementias,” she noted.

“It is also possible that there are issues related to unequal access and/or vaccine hesitancy and how this may influence the study population and the research results,” Dr. Snyder said.

The study had no specific funding. Dr. Bukhbinder and Dr. Snyder disclosed no relevant financial relationships.

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

A new study provides more evidence that influenza vaccination may help protect older adults against Alzheimer’s disease (AD).

In a large propensity-matched cohort of older adults, those who had received at least one influenza inoculation were 40% less likely than unvaccinated peers to develop AD over the course of 4 years.

“Influenza infection can cause serious health complications, particularly in adults 65 and older. Our study’s findings – that vaccination against the flu virus may also reduce the risk of Alzheimer’s dementia for at least a few years – adds to the already compelling reasons get the flu vaccine annually,” Avram Bukhbinder, MD, of the University of Texas, Houston, said in an interview.

The new findings support earlier work by the same researchers that also suggested a protective effect of flu vaccination on dementia risk.

The latest study was published online in the Journal of Alzheimer’s Disease.
 

40% lower risk

Prior studies have found a lower risk of dementia of any etiology following influenza vaccination in selected populations, including veterans and patients with serious chronic health conditions.

However, the effect of influenza vaccination on AD risk in a general cohort of older U.S. adults has not been characterized.

Dr. Bukhbinder and colleagues used claims data to create a propensity-matched cohort of 935,887 influenza-vaccinated adults and a like number of unvaccinated adults aged 65 and older.

The median age of the persons in the matched sample was 73.7 years, and 57% were women. All were free of dementia during the 6-year look-back study period.

During median follow-up of 46 months, 47,889 (5.1%) flu-vaccinated adults and 79,630 (8.5%) unvaccinated adults developed AD.

The risk of AD was 40% lower in the vaccinated group (relative risk, 0.60; 95% confidence interval, 0.59-0.61). The absolute risk reduction was 0.034 (95% CI, 0.033-0.035), corresponding to a number needed to treat of 29.4.
 

Mechanism unclear

“Our study does not address the mechanism(s) underlying the apparent effect of influenza vaccination on Alzheimer’s risk, but we look forward to future research investigating this important question,” Dr. Bukhbinder said.

“One possible mechanism is that, by helping to prevent or mitigate infection with the flu virus and the systemic inflammation that follows such an infection, the flu vaccine helps to decrease the systemic inflammation that may have otherwise occurred,” he explained.

It’s also possible that influenza vaccination may trigger non–influenza-specific changes in the immune system that help to reduce the damage caused by AD pathology, including amyloid plaques and neurofibrillary tangles, he said.

“For example, the influenza vaccine may alter the brain’s immune cells such that they are better at clearing Alzheimer’s pathologies, an effect that has been seen in mice, or it may reprogram these immune cells to respond to Alzheimer’s pathologies in ways that are less likely to damage nearby healthy brain cells, or it may do both,” Dr. Bukhbinder noted.
 

Alzheimer’s expert weighs in

Heather M. Snyder, PhD, vice president of medical and scientific relations for the Alzheimer’s Association, said this study “suggests that flu vaccination may be valuable for maintaining cognition and memory as we age. This is even more relevant today in the COVID-19 environment.

“It is too early to tell if getting flu vaccine, on its own, can reduce risk of Alzheimer’s. More research is needed to understand the biological mechanisms behind the results in this study,” Dr. Snyder said in an interview.

“For example, it is possible that people who are getting vaccinated also take better care of their health in other ways, and these things add up to lower risk of Alzheimer’s and other dementias,” she noted.

“It is also possible that there are issues related to unequal access and/or vaccine hesitancy and how this may influence the study population and the research results,” Dr. Snyder said.

The study had no specific funding. Dr. Bukhbinder and Dr. Snyder disclosed no relevant financial relationships.

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

A new study provides more evidence that influenza vaccination may help protect older adults against Alzheimer’s disease (AD).

In a large propensity-matched cohort of older adults, those who had received at least one influenza inoculation were 40% less likely than unvaccinated peers to develop AD over the course of 4 years.

“Influenza infection can cause serious health complications, particularly in adults 65 and older. Our study’s findings – that vaccination against the flu virus may also reduce the risk of Alzheimer’s dementia for at least a few years – adds to the already compelling reasons get the flu vaccine annually,” Avram Bukhbinder, MD, of the University of Texas, Houston, said in an interview.

The new findings support earlier work by the same researchers that also suggested a protective effect of flu vaccination on dementia risk.

The latest study was published online in the Journal of Alzheimer’s Disease.
 

40% lower risk

Prior studies have found a lower risk of dementia of any etiology following influenza vaccination in selected populations, including veterans and patients with serious chronic health conditions.

However, the effect of influenza vaccination on AD risk in a general cohort of older U.S. adults has not been characterized.

Dr. Bukhbinder and colleagues used claims data to create a propensity-matched cohort of 935,887 influenza-vaccinated adults and a like number of unvaccinated adults aged 65 and older.

The median age of the persons in the matched sample was 73.7 years, and 57% were women. All were free of dementia during the 6-year look-back study period.

During median follow-up of 46 months, 47,889 (5.1%) flu-vaccinated adults and 79,630 (8.5%) unvaccinated adults developed AD.

The risk of AD was 40% lower in the vaccinated group (relative risk, 0.60; 95% confidence interval, 0.59-0.61). The absolute risk reduction was 0.034 (95% CI, 0.033-0.035), corresponding to a number needed to treat of 29.4.
 

Mechanism unclear

“Our study does not address the mechanism(s) underlying the apparent effect of influenza vaccination on Alzheimer’s risk, but we look forward to future research investigating this important question,” Dr. Bukhbinder said.

“One possible mechanism is that, by helping to prevent or mitigate infection with the flu virus and the systemic inflammation that follows such an infection, the flu vaccine helps to decrease the systemic inflammation that may have otherwise occurred,” he explained.

It’s also possible that influenza vaccination may trigger non–influenza-specific changes in the immune system that help to reduce the damage caused by AD pathology, including amyloid plaques and neurofibrillary tangles, he said.

“For example, the influenza vaccine may alter the brain’s immune cells such that they are better at clearing Alzheimer’s pathologies, an effect that has been seen in mice, or it may reprogram these immune cells to respond to Alzheimer’s pathologies in ways that are less likely to damage nearby healthy brain cells, or it may do both,” Dr. Bukhbinder noted.
 

Alzheimer’s expert weighs in

Heather M. Snyder, PhD, vice president of medical and scientific relations for the Alzheimer’s Association, said this study “suggests that flu vaccination may be valuable for maintaining cognition and memory as we age. This is even more relevant today in the COVID-19 environment.

“It is too early to tell if getting flu vaccine, on its own, can reduce risk of Alzheimer’s. More research is needed to understand the biological mechanisms behind the results in this study,” Dr. Snyder said in an interview.

“For example, it is possible that people who are getting vaccinated also take better care of their health in other ways, and these things add up to lower risk of Alzheimer’s and other dementias,” she noted.

“It is also possible that there are issues related to unequal access and/or vaccine hesitancy and how this may influence the study population and the research results,” Dr. Snyder said.

The study had no specific funding. Dr. Bukhbinder and Dr. Snyder disclosed no relevant financial relationships.

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

The Food and Drug Administration has issued a Class I recall for the CARESCAPE R860/Engstrom Carestation/Engstrom PRO Ventilator batteries. A total of 1,533 complaints allege that the batteries are draining much faster than expected, prompting manufacturer GE Healthcare to initiate the recall. There have been no injuries, and no deaths associated with the use of this device, according to an FDA corrected announcement.  

Health care personnel and those patients who receive breathing support with these ventilators should be cautious about using CARESCAPE battery products moving forward, the agency said.

This type of ventilator is primarily powered by plugging into a wall outlet, but it has the capability to operate on backup batteries. These batteries are not solely for emergency situations such as power outages, but are also for routine situations such as transporting a patient within the hospital. GE Healthcare supplies these backup batteries with the ventilator, and sells replacements when they run out.

However, if the ventilator loses power because of battery malfunction, the patient may lose access to oxygen, leading to hypoxia, which can lead to brain injury and death. Therefore, if these batteries drain quicker than anticipated, it may put the patient at risk.

To prevent this danger, GE Healthcare recommends customers perform a battery performance test after they see this notice and every 3 months following. Consumers should take extra precaution and make sure their batteries are charged following a long period of inactivity. If the device is inactive for a while, the company says users should keep it plugged in to avoid draining the battery. Batteries should be replaced at a minimum of every 3 years.

When these devices are still plugged into the wall, they’re safe to use, according to the FDA. But when using the backup power source, clinicians should make sure to have alternative routes for breathing support on hand, such as with a bag-valve mask system.

There are 4,222 of these possibly defective batteries currently on the market. They were distributed from April 2, 2019, through April 18 of this year, when GE Healthcare stopped distributing these products and began the recall process. Any issues with these products should be reported to the FDA’s MedWatch database or by sending a medical device notification acknowledgment response to GE at the email address listed at the bottom of the recall announcement.

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

This article was updated 7/6/22.

The Food and Drug Administration has issued a Class I recall for the CARESCAPE R860/Engstrom Carestation/Engstrom PRO Ventilator batteries. A total of 1,533 complaints allege that the batteries are draining much faster than expected, prompting manufacturer GE Healthcare to initiate the recall. There have been no injuries, and no deaths associated with the use of this device, according to an FDA corrected announcement.  

Health care personnel and those patients who receive breathing support with these ventilators should be cautious about using CARESCAPE battery products moving forward, the agency said.

This type of ventilator is primarily powered by plugging into a wall outlet, but it has the capability to operate on backup batteries. These batteries are not solely for emergency situations such as power outages, but are also for routine situations such as transporting a patient within the hospital. GE Healthcare supplies these backup batteries with the ventilator, and sells replacements when they run out.

However, if the ventilator loses power because of battery malfunction, the patient may lose access to oxygen, leading to hypoxia, which can lead to brain injury and death. Therefore, if these batteries drain quicker than anticipated, it may put the patient at risk.

To prevent this danger, GE Healthcare recommends customers perform a battery performance test after they see this notice and every 3 months following. Consumers should take extra precaution and make sure their batteries are charged following a long period of inactivity. If the device is inactive for a while, the company says users should keep it plugged in to avoid draining the battery. Batteries should be replaced at a minimum of every 3 years.

When these devices are still plugged into the wall, they’re safe to use, according to the FDA. But when using the backup power source, clinicians should make sure to have alternative routes for breathing support on hand, such as with a bag-valve mask system.

There are 4,222 of these possibly defective batteries currently on the market. They were distributed from April 2, 2019, through April 18 of this year, when GE Healthcare stopped distributing these products and began the recall process. Any issues with these products should be reported to the FDA’s MedWatch database or by sending a medical device notification acknowledgment response to GE at the email address listed at the bottom of the recall announcement.

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

This article was updated 7/6/22.

The Food and Drug Administration has issued a Class I recall for the CARESCAPE R860/Engstrom Carestation/Engstrom PRO Ventilator batteries. A total of 1,533 complaints allege that the batteries are draining much faster than expected, prompting manufacturer GE Healthcare to initiate the recall. There have been no injuries, and no deaths associated with the use of this device, according to an FDA corrected announcement.  

Health care personnel and those patients who receive breathing support with these ventilators should be cautious about using CARESCAPE battery products moving forward, the agency said.

This type of ventilator is primarily powered by plugging into a wall outlet, but it has the capability to operate on backup batteries. These batteries are not solely for emergency situations such as power outages, but are also for routine situations such as transporting a patient within the hospital. GE Healthcare supplies these backup batteries with the ventilator, and sells replacements when they run out.

However, if the ventilator loses power because of battery malfunction, the patient may lose access to oxygen, leading to hypoxia, which can lead to brain injury and death. Therefore, if these batteries drain quicker than anticipated, it may put the patient at risk.

To prevent this danger, GE Healthcare recommends customers perform a battery performance test after they see this notice and every 3 months following. Consumers should take extra precaution and make sure their batteries are charged following a long period of inactivity. If the device is inactive for a while, the company says users should keep it plugged in to avoid draining the battery. Batteries should be replaced at a minimum of every 3 years.

When these devices are still plugged into the wall, they’re safe to use, according to the FDA. But when using the backup power source, clinicians should make sure to have alternative routes for breathing support on hand, such as with a bag-valve mask system.

There are 4,222 of these possibly defective batteries currently on the market. They were distributed from April 2, 2019, through April 18 of this year, when GE Healthcare stopped distributing these products and began the recall process. Any issues with these products should be reported to the FDA’s MedWatch database or by sending a medical device notification acknowledgment response to GE at the email address listed at the bottom of the recall announcement.

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

This article was updated 7/6/22.

The Food and Drug Administration has changed the warning about the Volara system to a Class I recall, the most severe level of recall, which is reserved for products that may cause injury or death. At the time of the warning, one injury had been associated with the product; as of June 23, there have been two deaths and one complaint, according to the FDA’s release.

Normally, the Volara system is used for breathing treatments that are administered at home. The medical device company that manufactures it, Baxter International, says the product is designed to help expand the airways and clear mucus for patients who use it. But because of recent product malfunctions, patients are at risk of choking on mucus, developing an infection in their lungs that cuts off their ability to take in oxygen, or in the worst cases, developing brain injury and death.

The risk is especially high because Volara is designed to be used in outpatient settings, not in the hospital under the supervision of a health care professional. It’s supposed to require less supervision than other ventilators. But if there is a problem with the device, or if it’s not connected properly, or if no one is available to assist, people are more likely to be harmed.

People who use the Volara ventilator system at home or people who assist in the use of it should be on alert for these problems. But the FDA advises that patients continue using the therapy if the device has been recommended by a doctor. The device should be used with extra precaution, and patients should be monitored for signs of distress, the release says. Problems while using the device should be reported to the FDA’s Medwatch database.

In addition to these reports, Baxter and its subsidiary company Hillrom say they will update the instructions for the device and will dispatch trainers to make home visits for users. The contact information for the company, as well as additional resources, are listed at the bottom of the release.

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

The Food and Drug Administration has changed the warning about the Volara system to a Class I recall, the most severe level of recall, which is reserved for products that may cause injury or death. At the time of the warning, one injury had been associated with the product; as of June 23, there have been two deaths and one complaint, according to the FDA’s release.

Normally, the Volara system is used for breathing treatments that are administered at home. The medical device company that manufactures it, Baxter International, says the product is designed to help expand the airways and clear mucus for patients who use it. But because of recent product malfunctions, patients are at risk of choking on mucus, developing an infection in their lungs that cuts off their ability to take in oxygen, or in the worst cases, developing brain injury and death.

The risk is especially high because Volara is designed to be used in outpatient settings, not in the hospital under the supervision of a health care professional. It’s supposed to require less supervision than other ventilators. But if there is a problem with the device, or if it’s not connected properly, or if no one is available to assist, people are more likely to be harmed.

People who use the Volara ventilator system at home or people who assist in the use of it should be on alert for these problems. But the FDA advises that patients continue using the therapy if the device has been recommended by a doctor. The device should be used with extra precaution, and patients should be monitored for signs of distress, the release says. Problems while using the device should be reported to the FDA’s Medwatch database.

In addition to these reports, Baxter and its subsidiary company Hillrom say they will update the instructions for the device and will dispatch trainers to make home visits for users. The contact information for the company, as well as additional resources, are listed at the bottom of the release.

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

The Food and Drug Administration has changed the warning about the Volara system to a Class I recall, the most severe level of recall, which is reserved for products that may cause injury or death. At the time of the warning, one injury had been associated with the product; as of June 23, there have been two deaths and one complaint, according to the FDA’s release.

Normally, the Volara system is used for breathing treatments that are administered at home. The medical device company that manufactures it, Baxter International, says the product is designed to help expand the airways and clear mucus for patients who use it. But because of recent product malfunctions, patients are at risk of choking on mucus, developing an infection in their lungs that cuts off their ability to take in oxygen, or in the worst cases, developing brain injury and death.

The risk is especially high because Volara is designed to be used in outpatient settings, not in the hospital under the supervision of a health care professional. It’s supposed to require less supervision than other ventilators. But if there is a problem with the device, or if it’s not connected properly, or if no one is available to assist, people are more likely to be harmed.

People who use the Volara ventilator system at home or people who assist in the use of it should be on alert for these problems. But the FDA advises that patients continue using the therapy if the device has been recommended by a doctor. The device should be used with extra precaution, and patients should be monitored for signs of distress, the release says. Problems while using the device should be reported to the FDA’s Medwatch database.

In addition to these reports, Baxter and its subsidiary company Hillrom say they will update the instructions for the device and will dispatch trainers to make home visits for users. The contact information for the company, as well as additional resources, are listed at the bottom of the release.

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

The Food and Drug Administration has ordered Juul Labs to stop selling e-cigarettes and vaping products on the U.S. market, the agency announced June 23.

The marketing denial order covers all the company’s products in the United States, which means Juul must stop distributing the products and remove everything on the market. That includes the Juul device and flavor replacement pods in the tobacco and menthol flavors.

“Today’s action is further progress on the FDA’s commitment to ensuring that all e-cigarette and electronic nicotine delivery system products currently being marketed to consumers meet our public health standards,” Robert Califf, MD, the FDA commissioner, said in the announcement.

“The agency has dedicated significant resources to review products from the companies that account for most of the U.S. market,” he said. “We recognize these make up a significant part of the available products and many have played a disproportionate role in the rise in youth vaping.”

The marketing denial order covers only the commercial distribution and retail sale of Juul’s products and doesn’t restrict consumer possession or use. The FDA “cannot and will not” enforce actions against consumers, the agency said.

The order comes after a 2-year review of the company’s application seeking authorization to continue selling non–fruit-flavored products, such as menthol and tobacco. The FDA determined the application “lacked sufficient evidence regarding the toxicological profile of the products to demonstrate that marketing of the products would be appropriate for the protection of the public health.”

Some of Juul’s study findings raised concerns because of “insufficient and conflicting data,” the FDA said, including potentially harmful chemicals leaching from the Juul liquid replacement pods.

“To date, the FDA has not received clinical information to suggest an immediate hazard associated with the use of the JUUL device or JUUL pods,” the agency said. “However, the [orders] issued today reflect FDA’s determination that there is insufficient evidence to assess the potential toxicological risks of using the JUUL products.”

Juul is expected to appeal the FDA’s decision, according to The New York Times.

In recent years, the FDA has reviewed marketing applications from Juul and other e-cigarette companies as anti-tobacco groups have called for new rules to limit products that led to a surge in youth vaping during the past decade. At the same time, advocates of e-cigarettes and nicotine-delivery devices have said the products help adult smokers to quit cigarettes and other tobacco products.

Juul, in particular, has been blamed for fueling the surge in underage vaping due to fruity flavors and hip marketing, according to The Wall Street Journal. The company removed sweet and fruity flavors from shelves in 2019 and has been trying to repair its reputation by limiting its marketing and focusing on adult cigarette smokers.

In 2020, all e-cigarette manufacturers in the United States were required to submit their products for FDA review to stay on the market, the newspaper reported. The agency has been weighing the potential benefits for adult cigarette smokers against the harms for young people.

The FDA banned the sale of fruit- and mint-flavored cartridges and juice pods in 2020, but menthol and tobacco-flavored products were left on the market, according to USA Today. In September 2021, the agency also banned the sale of hundreds of thousands of vaping and e-cigarette products but didn’t rule on Juul.

Meanwhile, the FDA has cleared Reynolds American and NJOY Holdings – two of Juul’s biggest rivals – to keep tobacco-flavored products on the market. Industry experts expected Juul to receive similar clearance, the Journal reported.

Juul, which was at the top of the U.S. e-cigarette market in 2018, has moved to second place behind Reynolds’s Vuse brand, the newspaper reported. The United States represents most of the company’s revenue, though its products are also available in Canada, the United Kingdom, France, Italy, and the Philippines.

Underage vaping has fallen in the United States since federal restrictions raised the legal purchase age for tobacco products to 21 and banned the sale of sweet and fruity cartridges, according to the Journal. Juul’s popularity has also dropped among youth, with other products such as Puff Bar, Vuse, and Smok becoming more popular among e-cigarette users in high school.

In a separate decision announced this week, the FDA is also moving forward with a plan to reduce the amount of nicotine in cigarettes. The decision, which has been years in the making, is aimed at prompting millions of cigarette users to quit smoking or switch to alternatives such as e-cigarettes, as well as limit the number of users who pick up smoking at an early age.

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

The Food and Drug Administration has ordered Juul Labs to stop selling e-cigarettes and vaping products on the U.S. market, the agency announced June 23.

The marketing denial order covers all the company’s products in the United States, which means Juul must stop distributing the products and remove everything on the market. That includes the Juul device and flavor replacement pods in the tobacco and menthol flavors.

“Today’s action is further progress on the FDA’s commitment to ensuring that all e-cigarette and electronic nicotine delivery system products currently being marketed to consumers meet our public health standards,” Robert Califf, MD, the FDA commissioner, said in the announcement.

“The agency has dedicated significant resources to review products from the companies that account for most of the U.S. market,” he said. “We recognize these make up a significant part of the available products and many have played a disproportionate role in the rise in youth vaping.”

The marketing denial order covers only the commercial distribution and retail sale of Juul’s products and doesn’t restrict consumer possession or use. The FDA “cannot and will not” enforce actions against consumers, the agency said.

The order comes after a 2-year review of the company’s application seeking authorization to continue selling non–fruit-flavored products, such as menthol and tobacco. The FDA determined the application “lacked sufficient evidence regarding the toxicological profile of the products to demonstrate that marketing of the products would be appropriate for the protection of the public health.”

Some of Juul’s study findings raised concerns because of “insufficient and conflicting data,” the FDA said, including potentially harmful chemicals leaching from the Juul liquid replacement pods.

“To date, the FDA has not received clinical information to suggest an immediate hazard associated with the use of the JUUL device or JUUL pods,” the agency said. “However, the [orders] issued today reflect FDA’s determination that there is insufficient evidence to assess the potential toxicological risks of using the JUUL products.”

Juul is expected to appeal the FDA’s decision, according to The New York Times.

In recent years, the FDA has reviewed marketing applications from Juul and other e-cigarette companies as anti-tobacco groups have called for new rules to limit products that led to a surge in youth vaping during the past decade. At the same time, advocates of e-cigarettes and nicotine-delivery devices have said the products help adult smokers to quit cigarettes and other tobacco products.

Juul, in particular, has been blamed for fueling the surge in underage vaping due to fruity flavors and hip marketing, according to The Wall Street Journal. The company removed sweet and fruity flavors from shelves in 2019 and has been trying to repair its reputation by limiting its marketing and focusing on adult cigarette smokers.

In 2020, all e-cigarette manufacturers in the United States were required to submit their products for FDA review to stay on the market, the newspaper reported. The agency has been weighing the potential benefits for adult cigarette smokers against the harms for young people.

The FDA banned the sale of fruit- and mint-flavored cartridges and juice pods in 2020, but menthol and tobacco-flavored products were left on the market, according to USA Today. In September 2021, the agency also banned the sale of hundreds of thousands of vaping and e-cigarette products but didn’t rule on Juul.

Meanwhile, the FDA has cleared Reynolds American and NJOY Holdings – two of Juul’s biggest rivals – to keep tobacco-flavored products on the market. Industry experts expected Juul to receive similar clearance, the Journal reported.

Juul, which was at the top of the U.S. e-cigarette market in 2018, has moved to second place behind Reynolds’s Vuse brand, the newspaper reported. The United States represents most of the company’s revenue, though its products are also available in Canada, the United Kingdom, France, Italy, and the Philippines.

Underage vaping has fallen in the United States since federal restrictions raised the legal purchase age for tobacco products to 21 and banned the sale of sweet and fruity cartridges, according to the Journal. Juul’s popularity has also dropped among youth, with other products such as Puff Bar, Vuse, and Smok becoming more popular among e-cigarette users in high school.

In a separate decision announced this week, the FDA is also moving forward with a plan to reduce the amount of nicotine in cigarettes. The decision, which has been years in the making, is aimed at prompting millions of cigarette users to quit smoking or switch to alternatives such as e-cigarettes, as well as limit the number of users who pick up smoking at an early age.

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

The Food and Drug Administration has ordered Juul Labs to stop selling e-cigarettes and vaping products on the U.S. market, the agency announced June 23.

The marketing denial order covers all the company’s products in the United States, which means Juul must stop distributing the products and remove everything on the market. That includes the Juul device and flavor replacement pods in the tobacco and menthol flavors.

“Today’s action is further progress on the FDA’s commitment to ensuring that all e-cigarette and electronic nicotine delivery system products currently being marketed to consumers meet our public health standards,” Robert Califf, MD, the FDA commissioner, said in the announcement.

“The agency has dedicated significant resources to review products from the companies that account for most of the U.S. market,” he said. “We recognize these make up a significant part of the available products and many have played a disproportionate role in the rise in youth vaping.”

The marketing denial order covers only the commercial distribution and retail sale of Juul’s products and doesn’t restrict consumer possession or use. The FDA “cannot and will not” enforce actions against consumers, the agency said.

The order comes after a 2-year review of the company’s application seeking authorization to continue selling non–fruit-flavored products, such as menthol and tobacco. The FDA determined the application “lacked sufficient evidence regarding the toxicological profile of the products to demonstrate that marketing of the products would be appropriate for the protection of the public health.”

Some of Juul’s study findings raised concerns because of “insufficient and conflicting data,” the FDA said, including potentially harmful chemicals leaching from the Juul liquid replacement pods.

“To date, the FDA has not received clinical information to suggest an immediate hazard associated with the use of the JUUL device or JUUL pods,” the agency said. “However, the [orders] issued today reflect FDA’s determination that there is insufficient evidence to assess the potential toxicological risks of using the JUUL products.”

Juul is expected to appeal the FDA’s decision, according to The New York Times.

In recent years, the FDA has reviewed marketing applications from Juul and other e-cigarette companies as anti-tobacco groups have called for new rules to limit products that led to a surge in youth vaping during the past decade. At the same time, advocates of e-cigarettes and nicotine-delivery devices have said the products help adult smokers to quit cigarettes and other tobacco products.

Juul, in particular, has been blamed for fueling the surge in underage vaping due to fruity flavors and hip marketing, according to The Wall Street Journal. The company removed sweet and fruity flavors from shelves in 2019 and has been trying to repair its reputation by limiting its marketing and focusing on adult cigarette smokers.

In 2020, all e-cigarette manufacturers in the United States were required to submit their products for FDA review to stay on the market, the newspaper reported. The agency has been weighing the potential benefits for adult cigarette smokers against the harms for young people.

The FDA banned the sale of fruit- and mint-flavored cartridges and juice pods in 2020, but menthol and tobacco-flavored products were left on the market, according to USA Today. In September 2021, the agency also banned the sale of hundreds of thousands of vaping and e-cigarette products but didn’t rule on Juul.

Meanwhile, the FDA has cleared Reynolds American and NJOY Holdings – two of Juul’s biggest rivals – to keep tobacco-flavored products on the market. Industry experts expected Juul to receive similar clearance, the Journal reported.

Juul, which was at the top of the U.S. e-cigarette market in 2018, has moved to second place behind Reynolds’s Vuse brand, the newspaper reported. The United States represents most of the company’s revenue, though its products are also available in Canada, the United Kingdom, France, Italy, and the Philippines.

Underage vaping has fallen in the United States since federal restrictions raised the legal purchase age for tobacco products to 21 and banned the sale of sweet and fruity cartridges, according to the Journal. Juul’s popularity has also dropped among youth, with other products such as Puff Bar, Vuse, and Smok becoming more popular among e-cigarette users in high school.

In a separate decision announced this week, the FDA is also moving forward with a plan to reduce the amount of nicotine in cigarettes. The decision, which has been years in the making, is aimed at prompting millions of cigarette users to quit smoking or switch to alternatives such as e-cigarettes, as well as limit the number of users who pick up smoking at an early age.

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

Adults in the United States increasingly perceive electronic cigarettes, or e-cigarettes, as “more harmful” than traditional cigarettes, according to a new study published in the American Journal of Preventive Medicine.

In addition, the percentage of people who exclusively used traditional cigarettes almost doubled between 2019 and 2020 among those who perceived e-cigarettes as more harmful, jumping from 8.4% in 2019 to 16.3% in 2020.

“We were able to show that these changes in perception potentially changed behaviors on a population level,” said Priti Bandi, PhD, principal scientist at the American Cancer Society in Atlanta and lead author of the study.

Since e-cigarettes entered the U.S. market in 2006, public health experts have questioned claims from manufacturers that the products work as a harm reduction tool to help traditional cigarette smokers to quit. Public perceptions have generally been that e-cigarettes are safer for a person’s health. While the research is still emerging on the long-term health outcomes of users, public opinion has shifted since the introduction of the devices.

The new study showed a sharp change in public perception of e-cigarettes following media coverage of cases of users who presented to emergency rooms with mysterious lung symptoms in 2019. The Centers for Disease Control and Prevention eventually found that what are now called e-cigarette or vaping product use–associated lung injuries were linked to vitamin E acetate, an additive to tetrahydrocannabinol-containing products but not nicotine.

The last update from the CDC came in February 2020, shortly before the COVID-19 pandemic swept through the United States, prompting a sharp shift to investigate the new virus among both health care providers and researchers.

Dr. Bandi and colleagues gathered 2018-2020 data from a National Institutes of Health database called the Health Information National Trends Survey, a mail-based, nationally representative, cross-sectional survey of U.S. adults and their attitudes of cancer and health-related information. More than 3,000 people each year responded to questions about e-cigarettes.

The study found that the percentage of people who believed e-cigarettes to be more harmful than traditional cigarettes more than tripled from 6.8% in 2018 to 28.3% in 2020. Fewer people also viewed e-cigarettes as less harmful than traditional cigarettes, falling from 17.6% in 2018 to 11.4% in 2020. Fewer people also said they were unsure about which product was more harmful.

Among those who believed e-cigarettes were “relatively” less harmful than traditional cigarettes, use of e-cigarettes jumped from 15.3% in 2019 to 26.7% in 2020.
 

The implications

The main finding that people started smoking cigarettes when they thought e-cigarettes were more harmful should be a wake-up to public health officials and doctors who communicate health risks to patients, according to Dr. Bandi and other experts.

Messaging should be more nuanced, Dr. Bandi said. Many adults use e-cigarettes as a cessation tool, and she and other experts point to research that shows the products are, at least in the short-term, less harmful especially as a smoking cessation tool. Vapes are among the most popular tools people use when they want to quit smoking – with the majority of U.S. adults using vapes either partially or fully to quit, according to the CDC.

Some countries, such as England, are moving to allow doctors to prescribe e-cigarettes to help reduce smoking rates. United Kingdom regulatory authorities in 2021 said they’re considering allowing licensing the devices for use in smoking cessation.

“There is an absolute need for ongoing, accurate communication from public health authorities targeted toward the appropriate audiences,” Bandi said.

Ashley Brooks-Russell, PhD, MPH, associate professor at the University of Colorado at Denver, Aurora, said the finding that perceptions can change behavior is good news. However, the bad news is that adults overcorrected and switched to cigarettes, which are proven to cause cancer and other health conditions.

“We’re good in public health about messaging that cigarettes are bad, that tobacco is broadly harmful,” Dr. Brooks-Russell said in an interview. “We’re really bad at talking about lesser options, like if you’re going to smoke, e-cigarettes are less harmful.” 

But other health leaders warn that e-cigarettes might produce the same adverse health outcomes, or worse, as cigarettes. The only way researchers will gain a conclusive answer is decades into a patient’s life. Until then, it’s not clear if any potential benefit from smoking cessation will outweigh the risks.

“This research should remind healthcare providers to find out what products patients are using, how much, and if those patients experience health issues later on,” said Kevin McQueen, MHA, lead respiratory director at University of Colorado Health System and president of the Colorado Respiratory Care Society.

“My concern is that while people are starting to think e-cigarettes are more dangerous, some people still think they are safe – and we don’t know how much safer they are,” he said. “And we aren’t going to know until 10, 15, 20 years from now.”

All authors were employed by the American Cancer Society at the time of the study, which receives grants from private and corporate foundations, including foundations associated with companies in the health sector for research outside of the submitted work. The authors are not funded by or key personnel for any of these grants, and their salaries are solely funded through American Cancer Society funds. No other financial disclosures were reported.

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

Adults in the United States increasingly perceive electronic cigarettes, or e-cigarettes, as “more harmful” than traditional cigarettes, according to a new study published in the American Journal of Preventive Medicine.

In addition, the percentage of people who exclusively used traditional cigarettes almost doubled between 2019 and 2020 among those who perceived e-cigarettes as more harmful, jumping from 8.4% in 2019 to 16.3% in 2020.

“We were able to show that these changes in perception potentially changed behaviors on a population level,” said Priti Bandi, PhD, principal scientist at the American Cancer Society in Atlanta and lead author of the study.

Since e-cigarettes entered the U.S. market in 2006, public health experts have questioned claims from manufacturers that the products work as a harm reduction tool to help traditional cigarette smokers to quit. Public perceptions have generally been that e-cigarettes are safer for a person’s health. While the research is still emerging on the long-term health outcomes of users, public opinion has shifted since the introduction of the devices.

The new study showed a sharp change in public perception of e-cigarettes following media coverage of cases of users who presented to emergency rooms with mysterious lung symptoms in 2019. The Centers for Disease Control and Prevention eventually found that what are now called e-cigarette or vaping product use–associated lung injuries were linked to vitamin E acetate, an additive to tetrahydrocannabinol-containing products but not nicotine.

The last update from the CDC came in February 2020, shortly before the COVID-19 pandemic swept through the United States, prompting a sharp shift to investigate the new virus among both health care providers and researchers.

Dr. Bandi and colleagues gathered 2018-2020 data from a National Institutes of Health database called the Health Information National Trends Survey, a mail-based, nationally representative, cross-sectional survey of U.S. adults and their attitudes of cancer and health-related information. More than 3,000 people each year responded to questions about e-cigarettes.

The study found that the percentage of people who believed e-cigarettes to be more harmful than traditional cigarettes more than tripled from 6.8% in 2018 to 28.3% in 2020. Fewer people also viewed e-cigarettes as less harmful than traditional cigarettes, falling from 17.6% in 2018 to 11.4% in 2020. Fewer people also said they were unsure about which product was more harmful.

Among those who believed e-cigarettes were “relatively” less harmful than traditional cigarettes, use of e-cigarettes jumped from 15.3% in 2019 to 26.7% in 2020.
 

The implications

The main finding that people started smoking cigarettes when they thought e-cigarettes were more harmful should be a wake-up to public health officials and doctors who communicate health risks to patients, according to Dr. Bandi and other experts.

Messaging should be more nuanced, Dr. Bandi said. Many adults use e-cigarettes as a cessation tool, and she and other experts point to research that shows the products are, at least in the short-term, less harmful especially as a smoking cessation tool. Vapes are among the most popular tools people use when they want to quit smoking – with the majority of U.S. adults using vapes either partially or fully to quit, according to the CDC.

Some countries, such as England, are moving to allow doctors to prescribe e-cigarettes to help reduce smoking rates. United Kingdom regulatory authorities in 2021 said they’re considering allowing licensing the devices for use in smoking cessation.

“There is an absolute need for ongoing, accurate communication from public health authorities targeted toward the appropriate audiences,” Bandi said.

Ashley Brooks-Russell, PhD, MPH, associate professor at the University of Colorado at Denver, Aurora, said the finding that perceptions can change behavior is good news. However, the bad news is that adults overcorrected and switched to cigarettes, which are proven to cause cancer and other health conditions.

“We’re good in public health about messaging that cigarettes are bad, that tobacco is broadly harmful,” Dr. Brooks-Russell said in an interview. “We’re really bad at talking about lesser options, like if you’re going to smoke, e-cigarettes are less harmful.” 

But other health leaders warn that e-cigarettes might produce the same adverse health outcomes, or worse, as cigarettes. The only way researchers will gain a conclusive answer is decades into a patient’s life. Until then, it’s not clear if any potential benefit from smoking cessation will outweigh the risks.

“This research should remind healthcare providers to find out what products patients are using, how much, and if those patients experience health issues later on,” said Kevin McQueen, MHA, lead respiratory director at University of Colorado Health System and president of the Colorado Respiratory Care Society.

“My concern is that while people are starting to think e-cigarettes are more dangerous, some people still think they are safe – and we don’t know how much safer they are,” he said. “And we aren’t going to know until 10, 15, 20 years from now.”

All authors were employed by the American Cancer Society at the time of the study, which receives grants from private and corporate foundations, including foundations associated with companies in the health sector for research outside of the submitted work. The authors are not funded by or key personnel for any of these grants, and their salaries are solely funded through American Cancer Society funds. No other financial disclosures were reported.

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

Adults in the United States increasingly perceive electronic cigarettes, or e-cigarettes, as “more harmful” than traditional cigarettes, according to a new study published in the American Journal of Preventive Medicine.

In addition, the percentage of people who exclusively used traditional cigarettes almost doubled between 2019 and 2020 among those who perceived e-cigarettes as more harmful, jumping from 8.4% in 2019 to 16.3% in 2020.

“We were able to show that these changes in perception potentially changed behaviors on a population level,” said Priti Bandi, PhD, principal scientist at the American Cancer Society in Atlanta and lead author of the study.

Since e-cigarettes entered the U.S. market in 2006, public health experts have questioned claims from manufacturers that the products work as a harm reduction tool to help traditional cigarette smokers to quit. Public perceptions have generally been that e-cigarettes are safer for a person’s health. While the research is still emerging on the long-term health outcomes of users, public opinion has shifted since the introduction of the devices.

The new study showed a sharp change in public perception of e-cigarettes following media coverage of cases of users who presented to emergency rooms with mysterious lung symptoms in 2019. The Centers for Disease Control and Prevention eventually found that what are now called e-cigarette or vaping product use–associated lung injuries were linked to vitamin E acetate, an additive to tetrahydrocannabinol-containing products but not nicotine.

The last update from the CDC came in February 2020, shortly before the COVID-19 pandemic swept through the United States, prompting a sharp shift to investigate the new virus among both health care providers and researchers.

Dr. Bandi and colleagues gathered 2018-2020 data from a National Institutes of Health database called the Health Information National Trends Survey, a mail-based, nationally representative, cross-sectional survey of U.S. adults and their attitudes of cancer and health-related information. More than 3,000 people each year responded to questions about e-cigarettes.

The study found that the percentage of people who believed e-cigarettes to be more harmful than traditional cigarettes more than tripled from 6.8% in 2018 to 28.3% in 2020. Fewer people also viewed e-cigarettes as less harmful than traditional cigarettes, falling from 17.6% in 2018 to 11.4% in 2020. Fewer people also said they were unsure about which product was more harmful.

Among those who believed e-cigarettes were “relatively” less harmful than traditional cigarettes, use of e-cigarettes jumped from 15.3% in 2019 to 26.7% in 2020.
 

The implications

The main finding that people started smoking cigarettes when they thought e-cigarettes were more harmful should be a wake-up to public health officials and doctors who communicate health risks to patients, according to Dr. Bandi and other experts.

Messaging should be more nuanced, Dr. Bandi said. Many adults use e-cigarettes as a cessation tool, and she and other experts point to research that shows the products are, at least in the short-term, less harmful especially as a smoking cessation tool. Vapes are among the most popular tools people use when they want to quit smoking – with the majority of U.S. adults using vapes either partially or fully to quit, according to the CDC.

Some countries, such as England, are moving to allow doctors to prescribe e-cigarettes to help reduce smoking rates. United Kingdom regulatory authorities in 2021 said they’re considering allowing licensing the devices for use in smoking cessation.

“There is an absolute need for ongoing, accurate communication from public health authorities targeted toward the appropriate audiences,” Bandi said.

Ashley Brooks-Russell, PhD, MPH, associate professor at the University of Colorado at Denver, Aurora, said the finding that perceptions can change behavior is good news. However, the bad news is that adults overcorrected and switched to cigarettes, which are proven to cause cancer and other health conditions.

“We’re good in public health about messaging that cigarettes are bad, that tobacco is broadly harmful,” Dr. Brooks-Russell said in an interview. “We’re really bad at talking about lesser options, like if you’re going to smoke, e-cigarettes are less harmful.” 

But other health leaders warn that e-cigarettes might produce the same adverse health outcomes, or worse, as cigarettes. The only way researchers will gain a conclusive answer is decades into a patient’s life. Until then, it’s not clear if any potential benefit from smoking cessation will outweigh the risks.

“This research should remind healthcare providers to find out what products patients are using, how much, and if those patients experience health issues later on,” said Kevin McQueen, MHA, lead respiratory director at University of Colorado Health System and president of the Colorado Respiratory Care Society.

“My concern is that while people are starting to think e-cigarettes are more dangerous, some people still think they are safe – and we don’t know how much safer they are,” he said. “And we aren’t going to know until 10, 15, 20 years from now.”

All authors were employed by the American Cancer Society at the time of the study, which receives grants from private and corporate foundations, including foundations associated with companies in the health sector for research outside of the submitted work. The authors are not funded by or key personnel for any of these grants, and their salaries are solely funded through American Cancer Society funds. No other financial disclosures were reported.

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

The long-term health consequences of COVID-19 have refocused our attention on post–acute infection syndromes (PAIS), starting a discussion on the need for a complete understanding of multisystemic pathophysiology, clinical indicators, and the epidemiology of these syndromes, representing a significant blind spot in the field of medicine. A better understanding of these persistent symptom profiles, not only for post-acute sequelae of SARS-CoV-2 infection (PASC), better known as long COVID, but also for other diseases with unexplainable post-acute sequelae, would allow doctors to fine tune the diagnostic criteria. Having a clear definition and better understanding of post–acute infection symptoms is a necessary step toward developing an evidence-based, multidisciplinary management approach.

PAIS, PASC, or long COVID

The observation of unexplained chronic sequelae after SARS-CoV-2 is known as PASC or long COVID.

Long COVID has been reported as a syndrome in survivors of serious and critical disease, but the effects also persist over time for subjects who experienced a mild infection that did not require admission to hospital. This means that PASC, especially when occurring after a mild or moderate COVID-19 infection, shares many of the same characteristics as chronic diseases triggered by other pathogenic organisms, many of which have not been sufficiently clarified.

PAIS are characterized by a set of core symptoms centering on the following:

• Exertion intolerance
• Disproportionate levels of fatigue
• Neurocognitive and sensory impairment
• Flu-like symptoms
• Unrefreshing sleep
• Myalgia/arthralgia

A plethora of nonspecific symptoms are often present to various degrees.

These similarities suggest a unifying pathophysiology that needs to be elucidated to properly understand and manage postinfectious chronic disability.
 

Overview of PAIS

A detailed revision on what is currently known about PAIS was published in Nature Medicine. It provided various useful pieces of information to assist with the poor recognition of these conditions in clinical practice, a result of which is that patients might experience delayed or a complete lack of clinical care.

The following consolidated postinfection sequelae are mentioned:

• Q fever fatigue syndrome, which follows infection by the intracellular bacterium Coxiella burnetii
• Post-dengue fatigue syndrome, which can follow infection by the mosquito-borne dengue virus
• Fatiguing and rheumatic symptoms in a subset of individuals infected with chikungunya virus, a mosquito-borne virus that causes fever and joint pain in the acute phase
• Post-polio syndrome, which can emerge as many as 15-40 years after an initial poliomyelitis attack (similarly, some other neurotropic microbes, such as West Nile virus, might lead to persistent effects)
• Prolonged, debilitating, chronic symptoms have long been reported in a subset of patients after common and typically nonserious infections. For example, after mononucleosis, a condition generally caused by Epstein-Barr virus (EBV), and after an outbreak of Giardia lamblia, an intestinal parasite that usually causes acute intestinal illness. In fact, several studies identified the association of this outbreak of giardiasis with chronic fatigue, irritable bowel syndrome (IBS), and fibromyalgia persisting for many years.
• Views expressed in the literature regarding the frequency and the validity of posttreatment Lyme disease syndrome are divided. Although substantial evidence points to persistence of arthralgia, fatigue, and subjective neurocognitive impairments in a minority of patients with Lyme disease after the recommended antibiotic treatment, some of the early studies have failed to characterize the initial Lyme disease episode with sufficient rigor.

Symptoms and signs

The symptoms and signs which, based on the evidence available, are seen more frequently in health care checks may be characterized as the following:

• Exertion intolerance, fatigue
• Flu-like and ‘sickness behavior’ symptoms: fever, feverishness, muscle pain, feeling sick, malaise, sweating, irritability
• Neurological/neurocognitive symptoms: brain fog, impaired concentration or memory, trouble finding words
• Rheumatologic symptoms: chronic or recurrent joint pain
• Trigger-specific symptoms: for example, eye problems post Ebola, IBS post Giardia, anosmia and ageusia post COVID-19, motor disturbances post polio and post West Nile virus

Myalgic encephalomyelitis/chronic fatigue syndrome

Patients with this disorder experience worsening of symptoms following physical, cognitive, or emotional exertion above their (very low) tolerated limit. Other prominent features frequently observed in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are neurocognitive impairments (colloquially referred to as brain fog), unrefreshing sleep, pain, sensory disturbances, gastrointestinal issues, and various forms of dysautonomia. Up to 75% of ME/CFS cases report an infection-like episode preceding the onset of their illness. Postinfectious and postviral fatigue syndromes were originally postulated as subsets of chronic fatigue syndrome. However, there appears to be no clear consensus at present about whether these terms should be considered synonymous to the ME/CFS label or any of its subsets, or include a wider range of postinfectious fatigue conditions.

Practical diagnostic criteria

From a revision of the available criteria, it emerges that the diagnostic criteria for a PAIS should include not only the presence of symptoms, but ideally also the intensity, course, and constellation of symptoms within an individual, as the individual symptoms and symptom trajectories of PAIS vary over time, rendering a mere comparison of symptom presence at a single time point misleading. Furthermore, when a diagnosis of ME/CFS is made, attention should be given to the choice of diagnostic criteria, with preference given to the more conservative criteria, so as not to run the risk of overestimating the syndrome.

Asthenia is the cornerstone symptom for most epidemiological studies on PAIS, but it would be reductive to concentrate only on this rather than the other characteristics, such as the exacerbation of symptoms following exertion, together with other characteristic symptoms and signs that may allow for better identification of the overall, observable clinical picture in these postinfection syndromes, which have significant impacts on a patient’s quality of life.

This article was translated from Univadis Italy. A version of this article appeared on Medscape.com.

The long-term health consequences of COVID-19 have refocused our attention on post–acute infection syndromes (PAIS), starting a discussion on the need for a complete understanding of multisystemic pathophysiology, clinical indicators, and the epidemiology of these syndromes, representing a significant blind spot in the field of medicine. A better understanding of these persistent symptom profiles, not only for post-acute sequelae of SARS-CoV-2 infection (PASC), better known as long COVID, but also for other diseases with unexplainable post-acute sequelae, would allow doctors to fine tune the diagnostic criteria. Having a clear definition and better understanding of post–acute infection symptoms is a necessary step toward developing an evidence-based, multidisciplinary management approach.

PAIS, PASC, or long COVID

The observation of unexplained chronic sequelae after SARS-CoV-2 is known as PASC or long COVID.

Long COVID has been reported as a syndrome in survivors of serious and critical disease, but the effects also persist over time for subjects who experienced a mild infection that did not require admission to hospital. This means that PASC, especially when occurring after a mild or moderate COVID-19 infection, shares many of the same characteristics as chronic diseases triggered by other pathogenic organisms, many of which have not been sufficiently clarified.

PAIS are characterized by a set of core symptoms centering on the following:

• Exertion intolerance
• Disproportionate levels of fatigue
• Neurocognitive and sensory impairment
• Flu-like symptoms
• Unrefreshing sleep
• Myalgia/arthralgia

A plethora of nonspecific symptoms are often present to various degrees.

These similarities suggest a unifying pathophysiology that needs to be elucidated to properly understand and manage postinfectious chronic disability.
 

Overview of PAIS

A detailed revision on what is currently known about PAIS was published in Nature Medicine. It provided various useful pieces of information to assist with the poor recognition of these conditions in clinical practice, a result of which is that patients might experience delayed or a complete lack of clinical care.

The following consolidated postinfection sequelae are mentioned:

• Q fever fatigue syndrome, which follows infection by the intracellular bacterium Coxiella burnetii
• Post-dengue fatigue syndrome, which can follow infection by the mosquito-borne dengue virus
• Fatiguing and rheumatic symptoms in a subset of individuals infected with chikungunya virus, a mosquito-borne virus that causes fever and joint pain in the acute phase
• Post-polio syndrome, which can emerge as many as 15-40 years after an initial poliomyelitis attack (similarly, some other neurotropic microbes, such as West Nile virus, might lead to persistent effects)
• Prolonged, debilitating, chronic symptoms have long been reported in a subset of patients after common and typically nonserious infections. For example, after mononucleosis, a condition generally caused by Epstein-Barr virus (EBV), and after an outbreak of Giardia lamblia, an intestinal parasite that usually causes acute intestinal illness. In fact, several studies identified the association of this outbreak of giardiasis with chronic fatigue, irritable bowel syndrome (IBS), and fibromyalgia persisting for many years.
• Views expressed in the literature regarding the frequency and the validity of posttreatment Lyme disease syndrome are divided. Although substantial evidence points to persistence of arthralgia, fatigue, and subjective neurocognitive impairments in a minority of patients with Lyme disease after the recommended antibiotic treatment, some of the early studies have failed to characterize the initial Lyme disease episode with sufficient rigor.

Symptoms and signs

The symptoms and signs which, based on the evidence available, are seen more frequently in health care checks may be characterized as the following:

• Exertion intolerance, fatigue
• Flu-like and ‘sickness behavior’ symptoms: fever, feverishness, muscle pain, feeling sick, malaise, sweating, irritability
• Neurological/neurocognitive symptoms: brain fog, impaired concentration or memory, trouble finding words
• Rheumatologic symptoms: chronic or recurrent joint pain
• Trigger-specific symptoms: for example, eye problems post Ebola, IBS post Giardia, anosmia and ageusia post COVID-19, motor disturbances post polio and post West Nile virus

Myalgic encephalomyelitis/chronic fatigue syndrome

Patients with this disorder experience worsening of symptoms following physical, cognitive, or emotional exertion above their (very low) tolerated limit. Other prominent features frequently observed in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are neurocognitive impairments (colloquially referred to as brain fog), unrefreshing sleep, pain, sensory disturbances, gastrointestinal issues, and various forms of dysautonomia. Up to 75% of ME/CFS cases report an infection-like episode preceding the onset of their illness. Postinfectious and postviral fatigue syndromes were originally postulated as subsets of chronic fatigue syndrome. However, there appears to be no clear consensus at present about whether these terms should be considered synonymous to the ME/CFS label or any of its subsets, or include a wider range of postinfectious fatigue conditions.

Practical diagnostic criteria

From a revision of the available criteria, it emerges that the diagnostic criteria for a PAIS should include not only the presence of symptoms, but ideally also the intensity, course, and constellation of symptoms within an individual, as the individual symptoms and symptom trajectories of PAIS vary over time, rendering a mere comparison of symptom presence at a single time point misleading. Furthermore, when a diagnosis of ME/CFS is made, attention should be given to the choice of diagnostic criteria, with preference given to the more conservative criteria, so as not to run the risk of overestimating the syndrome.

Asthenia is the cornerstone symptom for most epidemiological studies on PAIS, but it would be reductive to concentrate only on this rather than the other characteristics, such as the exacerbation of symptoms following exertion, together with other characteristic symptoms and signs that may allow for better identification of the overall, observable clinical picture in these postinfection syndromes, which have significant impacts on a patient’s quality of life.

This article was translated from Univadis Italy. A version of this article appeared on Medscape.com.

The long-term health consequences of COVID-19 have refocused our attention on post–acute infection syndromes (PAIS), starting a discussion on the need for a complete understanding of multisystemic pathophysiology, clinical indicators, and the epidemiology of these syndromes, representing a significant blind spot in the field of medicine. A better understanding of these persistent symptom profiles, not only for post-acute sequelae of SARS-CoV-2 infection (PASC), better known as long COVID, but also for other diseases with unexplainable post-acute sequelae, would allow doctors to fine tune the diagnostic criteria. Having a clear definition and better understanding of post–acute infection symptoms is a necessary step toward developing an evidence-based, multidisciplinary management approach.

PAIS, PASC, or long COVID

The observation of unexplained chronic sequelae after SARS-CoV-2 is known as PASC or long COVID.

Long COVID has been reported as a syndrome in survivors of serious and critical disease, but the effects also persist over time for subjects who experienced a mild infection that did not require admission to hospital. This means that PASC, especially when occurring after a mild or moderate COVID-19 infection, shares many of the same characteristics as chronic diseases triggered by other pathogenic organisms, many of which have not been sufficiently clarified.

PAIS are characterized by a set of core symptoms centering on the following:

• Exertion intolerance
• Disproportionate levels of fatigue
• Neurocognitive and sensory impairment
• Flu-like symptoms
• Unrefreshing sleep
• Myalgia/arthralgia

A plethora of nonspecific symptoms are often present to various degrees.

These similarities suggest a unifying pathophysiology that needs to be elucidated to properly understand and manage postinfectious chronic disability.
 

Overview of PAIS

A detailed revision on what is currently known about PAIS was published in Nature Medicine. It provided various useful pieces of information to assist with the poor recognition of these conditions in clinical practice, a result of which is that patients might experience delayed or a complete lack of clinical care.

The following consolidated postinfection sequelae are mentioned:

• Q fever fatigue syndrome, which follows infection by the intracellular bacterium Coxiella burnetii
• Post-dengue fatigue syndrome, which can follow infection by the mosquito-borne dengue virus
• Fatiguing and rheumatic symptoms in a subset of individuals infected with chikungunya virus, a mosquito-borne virus that causes fever and joint pain in the acute phase
• Post-polio syndrome, which can emerge as many as 15-40 years after an initial poliomyelitis attack (similarly, some other neurotropic microbes, such as West Nile virus, might lead to persistent effects)
• Prolonged, debilitating, chronic symptoms have long been reported in a subset of patients after common and typically nonserious infections. For example, after mononucleosis, a condition generally caused by Epstein-Barr virus (EBV), and after an outbreak of Giardia lamblia, an intestinal parasite that usually causes acute intestinal illness. In fact, several studies identified the association of this outbreak of giardiasis with chronic fatigue, irritable bowel syndrome (IBS), and fibromyalgia persisting for many years.
• Views expressed in the literature regarding the frequency and the validity of posttreatment Lyme disease syndrome are divided. Although substantial evidence points to persistence of arthralgia, fatigue, and subjective neurocognitive impairments in a minority of patients with Lyme disease after the recommended antibiotic treatment, some of the early studies have failed to characterize the initial Lyme disease episode with sufficient rigor.

Symptoms and signs

The symptoms and signs which, based on the evidence available, are seen more frequently in health care checks may be characterized as the following:

• Exertion intolerance, fatigue
• Flu-like and ‘sickness behavior’ symptoms: fever, feverishness, muscle pain, feeling sick, malaise, sweating, irritability
• Neurological/neurocognitive symptoms: brain fog, impaired concentration or memory, trouble finding words
• Rheumatologic symptoms: chronic or recurrent joint pain
• Trigger-specific symptoms: for example, eye problems post Ebola, IBS post Giardia, anosmia and ageusia post COVID-19, motor disturbances post polio and post West Nile virus

Myalgic encephalomyelitis/chronic fatigue syndrome

Patients with this disorder experience worsening of symptoms following physical, cognitive, or emotional exertion above their (very low) tolerated limit. Other prominent features frequently observed in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are neurocognitive impairments (colloquially referred to as brain fog), unrefreshing sleep, pain, sensory disturbances, gastrointestinal issues, and various forms of dysautonomia. Up to 75% of ME/CFS cases report an infection-like episode preceding the onset of their illness. Postinfectious and postviral fatigue syndromes were originally postulated as subsets of chronic fatigue syndrome. However, there appears to be no clear consensus at present about whether these terms should be considered synonymous to the ME/CFS label or any of its subsets, or include a wider range of postinfectious fatigue conditions.

Practical diagnostic criteria

From a revision of the available criteria, it emerges that the diagnostic criteria for a PAIS should include not only the presence of symptoms, but ideally also the intensity, course, and constellation of symptoms within an individual, as the individual symptoms and symptom trajectories of PAIS vary over time, rendering a mere comparison of symptom presence at a single time point misleading. Furthermore, when a diagnosis of ME/CFS is made, attention should be given to the choice of diagnostic criteria, with preference given to the more conservative criteria, so as not to run the risk of overestimating the syndrome.

Asthenia is the cornerstone symptom for most epidemiological studies on PAIS, but it would be reductive to concentrate only on this rather than the other characteristics, such as the exacerbation of symptoms following exertion, together with other characteristic symptoms and signs that may allow for better identification of the overall, observable clinical picture in these postinfection syndromes, which have significant impacts on a patient’s quality of life.

This article was translated from Univadis Italy. A version of this article appeared on Medscape.com.

Treatment with an interleukin-6 neutralizing antibody significantly reduced airway mucus hypersecretion (AMH) in chronic obstructive pulmonary disease (COPD), based on data from human and mouse cells in a human organoid model.

AMH plays a large part in aggravating airway obstruction in patients with COPD, Yuan-Yuan Wei, MD, of First Affiliated Hospital of Anhui Medical University, Hefei, China, and colleagues wrote.

Current pharmacotherapies relieve COPD symptoms and improve exercise tolerance, but have not proven effective for relieving the airflow limitations caused by mucus accumulation that “leads to irreversible structural damage and an unfavorable prognosis,” the researchers said. Although reducing AMH could help manage COPD, the molecular mechanisms of action have not been fully explored.

In a study published in Biomedicine & Pharmacotherapy , the researchers examined the relationship between IL-6 and AMH. Since IL-6 has been shown to cause overexpression of the mucin-type protein known as Muc5ac, they hypothesized that IL-6 antibodies (IL-6Ab) might block this protein elevation.

The researchers recruited 30 adults with COPD and 30 controls from a single center. Bronchial epithelial cells were isolated from the participants and measured the levels of Muc5ac protein and mRNA in the lung tissue. Compared with controls, COPD patients had elevated Muc5ac positively correlated with IL-6.

The researchers then created an organoid model of a trachea for COPD patients and controls. In the model, Muc5ac was similarly elevated in COPD patients, compared with controls. “Furthermore, IL-6 significantly induced excessive secretion of mucus in the organoid model of trachea in COPD patients as observed under electron microscope, and IL-6Ab attenuated these effects,” they noted.

IL-6 significantly increased both Muc5ac mRNA and protein expression in the organoid model of trachea (P < .0001 and P < .005, respectively), but both of these significantly decreased when treated with IL-6Ab (P < .0001 and P < .05, respectively).

The researchers also examined human and mouse cells to explore the mechanism of action of IL-6Ab. Using high-throughput sequencing, they found that the IL-6Ab induced nuclear translocation of the Nrt2 gene in COPD patients, and that this action promoted the effect of IL-6Ab on excessive mucus secretion.

The study findings were limited by the relatively small study population from a single center, the researchers noted.

However, the results support the potential of IL-6Ab as “a novel therapeutic strategy in the treatment of IL-6–induced hypersecretion of airway mucus so as to improve airflow limitations in COPD,” they concluded.

The study was supported by supported by the National Natural Science Foundation of China and the Scientific Research Project of Education Department of Anhui Province. The researchers had no financial conflicts to disclose.

Treatment with an interleukin-6 neutralizing antibody significantly reduced airway mucus hypersecretion (AMH) in chronic obstructive pulmonary disease (COPD), based on data from human and mouse cells in a human organoid model.

AMH plays a large part in aggravating airway obstruction in patients with COPD, Yuan-Yuan Wei, MD, of First Affiliated Hospital of Anhui Medical University, Hefei, China, and colleagues wrote.

Current pharmacotherapies relieve COPD symptoms and improve exercise tolerance, but have not proven effective for relieving the airflow limitations caused by mucus accumulation that “leads to irreversible structural damage and an unfavorable prognosis,” the researchers said. Although reducing AMH could help manage COPD, the molecular mechanisms of action have not been fully explored.

In a study published in Biomedicine & Pharmacotherapy , the researchers examined the relationship between IL-6 and AMH. Since IL-6 has been shown to cause overexpression of the mucin-type protein known as Muc5ac, they hypothesized that IL-6 antibodies (IL-6Ab) might block this protein elevation.

The researchers recruited 30 adults with COPD and 30 controls from a single center. Bronchial epithelial cells were isolated from the participants and measured the levels of Muc5ac protein and mRNA in the lung tissue. Compared with controls, COPD patients had elevated Muc5ac positively correlated with IL-6.

The researchers then created an organoid model of a trachea for COPD patients and controls. In the model, Muc5ac was similarly elevated in COPD patients, compared with controls. “Furthermore, IL-6 significantly induced excessive secretion of mucus in the organoid model of trachea in COPD patients as observed under electron microscope, and IL-6Ab attenuated these effects,” they noted.

IL-6 significantly increased both Muc5ac mRNA and protein expression in the organoid model of trachea (P < .0001 and P < .005, respectively), but both of these significantly decreased when treated with IL-6Ab (P < .0001 and P < .05, respectively).

The researchers also examined human and mouse cells to explore the mechanism of action of IL-6Ab. Using high-throughput sequencing, they found that the IL-6Ab induced nuclear translocation of the Nrt2 gene in COPD patients, and that this action promoted the effect of IL-6Ab on excessive mucus secretion.

The study findings were limited by the relatively small study population from a single center, the researchers noted.

However, the results support the potential of IL-6Ab as “a novel therapeutic strategy in the treatment of IL-6–induced hypersecretion of airway mucus so as to improve airflow limitations in COPD,” they concluded.

The study was supported by supported by the National Natural Science Foundation of China and the Scientific Research Project of Education Department of Anhui Province. The researchers had no financial conflicts to disclose.

Treatment with an interleukin-6 neutralizing antibody significantly reduced airway mucus hypersecretion (AMH) in chronic obstructive pulmonary disease (COPD), based on data from human and mouse cells in a human organoid model.

AMH plays a large part in aggravating airway obstruction in patients with COPD, Yuan-Yuan Wei, MD, of First Affiliated Hospital of Anhui Medical University, Hefei, China, and colleagues wrote.

Current pharmacotherapies relieve COPD symptoms and improve exercise tolerance, but have not proven effective for relieving the airflow limitations caused by mucus accumulation that “leads to irreversible structural damage and an unfavorable prognosis,” the researchers said. Although reducing AMH could help manage COPD, the molecular mechanisms of action have not been fully explored.

In a study published in Biomedicine & Pharmacotherapy , the researchers examined the relationship between IL-6 and AMH. Since IL-6 has been shown to cause overexpression of the mucin-type protein known as Muc5ac, they hypothesized that IL-6 antibodies (IL-6Ab) might block this protein elevation.

The researchers recruited 30 adults with COPD and 30 controls from a single center. Bronchial epithelial cells were isolated from the participants and measured the levels of Muc5ac protein and mRNA in the lung tissue. Compared with controls, COPD patients had elevated Muc5ac positively correlated with IL-6.

The researchers then created an organoid model of a trachea for COPD patients and controls. In the model, Muc5ac was similarly elevated in COPD patients, compared with controls. “Furthermore, IL-6 significantly induced excessive secretion of mucus in the organoid model of trachea in COPD patients as observed under electron microscope, and IL-6Ab attenuated these effects,” they noted.

IL-6 significantly increased both Muc5ac mRNA and protein expression in the organoid model of trachea (P < .0001 and P < .005, respectively), but both of these significantly decreased when treated with IL-6Ab (P < .0001 and P < .05, respectively).

The researchers also examined human and mouse cells to explore the mechanism of action of IL-6Ab. Using high-throughput sequencing, they found that the IL-6Ab induced nuclear translocation of the Nrt2 gene in COPD patients, and that this action promoted the effect of IL-6Ab on excessive mucus secretion.

The study findings were limited by the relatively small study population from a single center, the researchers noted.

However, the results support the potential of IL-6Ab as “a novel therapeutic strategy in the treatment of IL-6–induced hypersecretion of airway mucus so as to improve airflow limitations in COPD,” they concluded.

The study was supported by supported by the National Natural Science Foundation of China and the Scientific Research Project of Education Department of Anhui Province. The researchers had no financial conflicts to disclose.