Pulmonology

For adults with acute hypoxemic respiratory failure (AHRF), treatment using a helmet interface is likely superior to a face mask interface, according to a systematic review of recent randomized controlled trials examining different noninvasive oxygenation strategies for AHRF treatment.

The meta-analysis of 36 trials) found also that helmet interface probably lowers mortality and risk of mechanical intervention, and reduces hospital and ICU stay.

The COVID-19 pandemic has underscored the benefits of optimizing noninvasive strategies to avoid unnecessary intubation. Intubation may be avoided in patients with AHRF through noninvasive oxygenation strategies, including high flow nasal cannula (HFNC), continuous positive airway pressure (CPAP) and noninvasive bilevel ventilation, noted Tyler Pitre, MD, department of medicine, McMaster University, Hamilton, Ont., and colleagues. CPAP and bilevel ventilation can be delivered through different interfaces, most commonly face mask or helmet. While research has shown noninvasive strategies to be associated with reductions in risk for invasive mechanical ventilation, mortality assessments and analyses comparing specific modalities (i.e., CPAP vs. bilevel ventilation) have been limited. The incremental reduction in diaphragmatic effort and improved gas exchange demonstrated for bilevel ventilation compared with CPAP in COPD patients suggests that responses in AHRF may differ for CPAP and bilevel ventilation, state Dr. Pitre and colleagues. On the other hand, the increased drive pressure of bilevel ventilation may compound patient self-induced lung injury with concomitant lung inflammation and need for prolonged respiratory support. New evidence from several large, high quality randomized controlled trials (RCTs) in COVID-19-related AHRF offered an opportunity to reassess comparative efficacies, the researchers noted.

The retrospective study encompassed RCTs with all types of AHRF, including COVID-19 related, with a total of 7,046 patients whose median age was 59.4 years (61.4% were males). Thirty of the 36 RCTs reported on mortality (6,114 patients and 1,539 deaths). The study’s analysis showed with moderate certainty that helmet CPAP reduces mortality (231 fewer deaths per 1,000 [95% confidence interval (CI), 126-273]) while the 63 fewer deaths per 1,000 (95% CI, 15-102) indicated with low certainty that HFNC may reduce mortality compared with standard oxygen therapy (SOT). The analysis showed also that face mask bilevel (36 fewer deaths per 1,000 [84.0 fewer to 24.0 more]) and helmet bilevel ventilation (129.0 fewer deaths per 1,000 [195.0 to 24.0 fewer]) may reduce death compared with SOT (all low certainty). The mortality benefit for face mask CPAP compared with SOT was uncertain (very low certainty) (9 fewer deaths per 1,000 [81 fewer deaths to 84 more]). For helmet CPAP vs. HFNC ventilation, the mortality benefit had moderate certainty (198.1 fewer events per 1,000 [95% CI, 69.75-248.31].
 

Mechanical ventilation and ICU duration

The authors found that HFNC probably reduces the need for invasive mechanical ventilation (103.5 fewer events per 1,000 [40.5-157.5 fewer]; moderate certainty). Helmet bilevel ventilation and helmet CPAP may reduce the duration of ICU stay compared with SOT (both low certainty) at (4.84 days fewer [95% CI 2.33 to 16 7.36 days fewer]) and (1.74 days fewer [95% CI 4.49 fewer to 1.01 more]), respectively. Also, SOT may be more comfortable than face mask noninvasive ventilation (NIV) and no different in comfort compared with HFNC (both low certainty).

“Helmet noninvasive ventilation interfaces is probably effective in acute hypoxic respiratory failure and is superior to face mask interfaces. All modalities including HFNC probably reduce the risk of need for invasive mechanical ventilation,” the researchers wrote.

“This meta-analysis shows that helmet noninvasive ventilation is effective in reducing death, and need for invasive mechanical ventilation based on a moderate certainty of evidence,” Shyamsunder Subramanian, MD, chief, division of pulmonary critical care and sleep medicine, Sutter Health, Tracy, Calif., said in an interview. “It is premature based on the results of this meta-analysis to conclude that guideline changes are needed. Use of helmet based ventilation remains limited in scope. We need appropriately designed prospective trials across multiple centers to get sufficient rigor of scientific evidence before any change in guidelines or practice recommendations can be formulated about the appropriate use of helmet NIV in acute respiratory failure.”

The researchers cited the relative heterogeneity of the population included in this analysis as a study limitation.

Dr. Pitre and Dr. Subramanian disclosed that they have no relevant conflicts of interest.

For adults with acute hypoxemic respiratory failure (AHRF), treatment using a helmet interface is likely superior to a face mask interface, according to a systematic review of recent randomized controlled trials examining different noninvasive oxygenation strategies for AHRF treatment.

The meta-analysis of 36 trials) found also that helmet interface probably lowers mortality and risk of mechanical intervention, and reduces hospital and ICU stay.

The COVID-19 pandemic has underscored the benefits of optimizing noninvasive strategies to avoid unnecessary intubation. Intubation may be avoided in patients with AHRF through noninvasive oxygenation strategies, including high flow nasal cannula (HFNC), continuous positive airway pressure (CPAP) and noninvasive bilevel ventilation, noted Tyler Pitre, MD, department of medicine, McMaster University, Hamilton, Ont., and colleagues. CPAP and bilevel ventilation can be delivered through different interfaces, most commonly face mask or helmet. While research has shown noninvasive strategies to be associated with reductions in risk for invasive mechanical ventilation, mortality assessments and analyses comparing specific modalities (i.e., CPAP vs. bilevel ventilation) have been limited. The incremental reduction in diaphragmatic effort and improved gas exchange demonstrated for bilevel ventilation compared with CPAP in COPD patients suggests that responses in AHRF may differ for CPAP and bilevel ventilation, state Dr. Pitre and colleagues. On the other hand, the increased drive pressure of bilevel ventilation may compound patient self-induced lung injury with concomitant lung inflammation and need for prolonged respiratory support. New evidence from several large, high quality randomized controlled trials (RCTs) in COVID-19-related AHRF offered an opportunity to reassess comparative efficacies, the researchers noted.

The retrospective study encompassed RCTs with all types of AHRF, including COVID-19 related, with a total of 7,046 patients whose median age was 59.4 years (61.4% were males). Thirty of the 36 RCTs reported on mortality (6,114 patients and 1,539 deaths). The study’s analysis showed with moderate certainty that helmet CPAP reduces mortality (231 fewer deaths per 1,000 [95% confidence interval (CI), 126-273]) while the 63 fewer deaths per 1,000 (95% CI, 15-102) indicated with low certainty that HFNC may reduce mortality compared with standard oxygen therapy (SOT). The analysis showed also that face mask bilevel (36 fewer deaths per 1,000 [84.0 fewer to 24.0 more]) and helmet bilevel ventilation (129.0 fewer deaths per 1,000 [195.0 to 24.0 fewer]) may reduce death compared with SOT (all low certainty). The mortality benefit for face mask CPAP compared with SOT was uncertain (very low certainty) (9 fewer deaths per 1,000 [81 fewer deaths to 84 more]). For helmet CPAP vs. HFNC ventilation, the mortality benefit had moderate certainty (198.1 fewer events per 1,000 [95% CI, 69.75-248.31].
 

Mechanical ventilation and ICU duration

The authors found that HFNC probably reduces the need for invasive mechanical ventilation (103.5 fewer events per 1,000 [40.5-157.5 fewer]; moderate certainty). Helmet bilevel ventilation and helmet CPAP may reduce the duration of ICU stay compared with SOT (both low certainty) at (4.84 days fewer [95% CI 2.33 to 16 7.36 days fewer]) and (1.74 days fewer [95% CI 4.49 fewer to 1.01 more]), respectively. Also, SOT may be more comfortable than face mask noninvasive ventilation (NIV) and no different in comfort compared with HFNC (both low certainty).

“Helmet noninvasive ventilation interfaces is probably effective in acute hypoxic respiratory failure and is superior to face mask interfaces. All modalities including HFNC probably reduce the risk of need for invasive mechanical ventilation,” the researchers wrote.

“This meta-analysis shows that helmet noninvasive ventilation is effective in reducing death, and need for invasive mechanical ventilation based on a moderate certainty of evidence,” Shyamsunder Subramanian, MD, chief, division of pulmonary critical care and sleep medicine, Sutter Health, Tracy, Calif., said in an interview. “It is premature based on the results of this meta-analysis to conclude that guideline changes are needed. Use of helmet based ventilation remains limited in scope. We need appropriately designed prospective trials across multiple centers to get sufficient rigor of scientific evidence before any change in guidelines or practice recommendations can be formulated about the appropriate use of helmet NIV in acute respiratory failure.”

The researchers cited the relative heterogeneity of the population included in this analysis as a study limitation.

Dr. Pitre and Dr. Subramanian disclosed that they have no relevant conflicts of interest.

For adults with acute hypoxemic respiratory failure (AHRF), treatment using a helmet interface is likely superior to a face mask interface, according to a systematic review of recent randomized controlled trials examining different noninvasive oxygenation strategies for AHRF treatment.

The meta-analysis of 36 trials) found also that helmet interface probably lowers mortality and risk of mechanical intervention, and reduces hospital and ICU stay.

The COVID-19 pandemic has underscored the benefits of optimizing noninvasive strategies to avoid unnecessary intubation. Intubation may be avoided in patients with AHRF through noninvasive oxygenation strategies, including high flow nasal cannula (HFNC), continuous positive airway pressure (CPAP) and noninvasive bilevel ventilation, noted Tyler Pitre, MD, department of medicine, McMaster University, Hamilton, Ont., and colleagues. CPAP and bilevel ventilation can be delivered through different interfaces, most commonly face mask or helmet. While research has shown noninvasive strategies to be associated with reductions in risk for invasive mechanical ventilation, mortality assessments and analyses comparing specific modalities (i.e., CPAP vs. bilevel ventilation) have been limited. The incremental reduction in diaphragmatic effort and improved gas exchange demonstrated for bilevel ventilation compared with CPAP in COPD patients suggests that responses in AHRF may differ for CPAP and bilevel ventilation, state Dr. Pitre and colleagues. On the other hand, the increased drive pressure of bilevel ventilation may compound patient self-induced lung injury with concomitant lung inflammation and need for prolonged respiratory support. New evidence from several large, high quality randomized controlled trials (RCTs) in COVID-19-related AHRF offered an opportunity to reassess comparative efficacies, the researchers noted.

The retrospective study encompassed RCTs with all types of AHRF, including COVID-19 related, with a total of 7,046 patients whose median age was 59.4 years (61.4% were males). Thirty of the 36 RCTs reported on mortality (6,114 patients and 1,539 deaths). The study’s analysis showed with moderate certainty that helmet CPAP reduces mortality (231 fewer deaths per 1,000 [95% confidence interval (CI), 126-273]) while the 63 fewer deaths per 1,000 (95% CI, 15-102) indicated with low certainty that HFNC may reduce mortality compared with standard oxygen therapy (SOT). The analysis showed also that face mask bilevel (36 fewer deaths per 1,000 [84.0 fewer to 24.0 more]) and helmet bilevel ventilation (129.0 fewer deaths per 1,000 [195.0 to 24.0 fewer]) may reduce death compared with SOT (all low certainty). The mortality benefit for face mask CPAP compared with SOT was uncertain (very low certainty) (9 fewer deaths per 1,000 [81 fewer deaths to 84 more]). For helmet CPAP vs. HFNC ventilation, the mortality benefit had moderate certainty (198.1 fewer events per 1,000 [95% CI, 69.75-248.31].
 

Mechanical ventilation and ICU duration

The authors found that HFNC probably reduces the need for invasive mechanical ventilation (103.5 fewer events per 1,000 [40.5-157.5 fewer]; moderate certainty). Helmet bilevel ventilation and helmet CPAP may reduce the duration of ICU stay compared with SOT (both low certainty) at (4.84 days fewer [95% CI 2.33 to 16 7.36 days fewer]) and (1.74 days fewer [95% CI 4.49 fewer to 1.01 more]), respectively. Also, SOT may be more comfortable than face mask noninvasive ventilation (NIV) and no different in comfort compared with HFNC (both low certainty).

“Helmet noninvasive ventilation interfaces is probably effective in acute hypoxic respiratory failure and is superior to face mask interfaces. All modalities including HFNC probably reduce the risk of need for invasive mechanical ventilation,” the researchers wrote.

“This meta-analysis shows that helmet noninvasive ventilation is effective in reducing death, and need for invasive mechanical ventilation based on a moderate certainty of evidence,” Shyamsunder Subramanian, MD, chief, division of pulmonary critical care and sleep medicine, Sutter Health, Tracy, Calif., said in an interview. “It is premature based on the results of this meta-analysis to conclude that guideline changes are needed. Use of helmet based ventilation remains limited in scope. We need appropriately designed prospective trials across multiple centers to get sufficient rigor of scientific evidence before any change in guidelines or practice recommendations can be formulated about the appropriate use of helmet NIV in acute respiratory failure.”

The researchers cited the relative heterogeneity of the population included in this analysis as a study limitation.

Dr. Pitre and Dr. Subramanian disclosed that they have no relevant conflicts of interest.

A recent Swedish study found that both abdominal and general obesity were independently associated with respiratory illnesses, including asthma and self-reported chronic obstructive pulmonary disease.

Relationships between respiratory conditions with characterized obesity types in adults were assessed using self-report surveys from participants originally enrolled in the European Community Respiratory Health Survey (ECRHS) investigating asthma, allergy, and risk factors. The Respiratory Health in Northern Europe (RHINE) III provides a second follow-up substudy of ECRHS focused on two forms of obesity associated with respiratory illnesses.

Obesity is a characteristic risk factor linked to respiratory ailments such as asthma and COPD. High body mass index (BMI) and waist circumference (WC) provide quantitative measurements for defining conditions of comprehensive general and abdominal obesity, respectively.

Although both types of obesity have been associated with asthma incidence, studies on their independent impact on this disease have been limited. Previous reports on abdominal obesity associated with asthma have been inconsistent when considering sexes in the analysis. Additionally, COPD and related outcomes differed between abdominal and general obesity, indicating a need to discover whether self-reported WC abdominal obesity and BMI-based general obesity are independently associated with respiratory symptoms, early- and late-onset asthma, COPD, chronic bronchitis, rhinitis, and sex, Marta A. Kisiel, MD, PhD, of the department of environmental and occupational medicine, Uppsala University, Sweden, and colleagues write.

In a prospective study published in the journal Respiratory Medicine, the researchers report on a cross-sectional investigation of responses to a questionnaire similar to one utilized 10 years earlier in the RHINE II study. Questions required simple yes/no responses that covered asthma, respiratory symptoms, allergic rhinitis, chronic bronchitis, and COPD. Additional requested information included age of asthma onset, potential confounding variables of age, smoking, physical activity, and highest education level, weight and height for BMI calculation, and WC measurement with instructions and a provided tape measure.

The population of the RHINE III study conducted from 2010 to 2012 was composed of 12,290 participants (53% response frequency) obtained from a total of seven research centers located in five northern European countries. Obesity categorization classified 1,837 (6.7%) participants as generally obese based on a high BMI ≥ 30 kg/m² and 4,261 (34.7%) as abdominally obese by WC measurements of ≥ 102 cm for men and ≥ 88 cm for women. Of the 4,261 total participants, 1,669 met both general and abdominal obesity criteria. Mean age was in the low 50s range and the obese population consisted of more women than men.

Simple linear regression revealed that BMI and WC were highly correlated, and both were associated with tested respiratory conditions when adjusted for confounding variables. Differences with respect to WC and BMI were independently associated with most of the examined respiratory conditions when WC was adjusted for BMI and vice versa. Neither early-onset asthma nor allergic rhinitis were associated with WC, BMI, or abdominal or general obesity.

A significantly high proportion of individuals with general and abdominal obesity experienced a variety of defined respiratory symptoms, and asthma, chronic bronchitis, or COPD. An independent association of abdominal obesity (with or without general obesity) was found to occur with respiratory symptoms, asthma, late-onset asthma, and chronic bronchitis.

After adjusting for abdominal obesity, general obesity showed an independent and significant association with respiratory symptoms, asthma, adult-onset asthma, and COPD. An analysis stratified by sex indicated a significant association of abdominal and general obesity with asthma in women presented as an odds ratio of 1.56 (95% confidence interval, 1.30-1.87) and 1.95 (95% CI, 1.56-2.43), respectively, compared with men, with an OR of 1.22 (95% CI, 0.97-3.17) and 1.28 (95% CI, 0.97-1.68), respectively. The association of abdominal and general obesity with COPD was also stronger in women, compared with men.

The researchers conclude that “both general and abdominal obesity [were], independent of each other, associated with respiratory symptoms in adults.” There is also a distinct difference between women and men for the association of self-reported asthma and COPD with abdominal and general obesity.

The large randomly selected sample size of participants from research centers located in five northern European countries was considered a major strength of this study as it permitted simultaneous adjustment for multiple potential confounders. Several limitations were acknowledged, including absence of data on obstructive respiratory disease severity, WC measurements not being performed by trained staff, and self-reported height and weight measurements.

The authors have disclosed no relevant financial relationships.

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

A recent Swedish study found that both abdominal and general obesity were independently associated with respiratory illnesses, including asthma and self-reported chronic obstructive pulmonary disease.

Relationships between respiratory conditions with characterized obesity types in adults were assessed using self-report surveys from participants originally enrolled in the European Community Respiratory Health Survey (ECRHS) investigating asthma, allergy, and risk factors. The Respiratory Health in Northern Europe (RHINE) III provides a second follow-up substudy of ECRHS focused on two forms of obesity associated with respiratory illnesses.

Obesity is a characteristic risk factor linked to respiratory ailments such as asthma and COPD. High body mass index (BMI) and waist circumference (WC) provide quantitative measurements for defining conditions of comprehensive general and abdominal obesity, respectively.

Although both types of obesity have been associated with asthma incidence, studies on their independent impact on this disease have been limited. Previous reports on abdominal obesity associated with asthma have been inconsistent when considering sexes in the analysis. Additionally, COPD and related outcomes differed between abdominal and general obesity, indicating a need to discover whether self-reported WC abdominal obesity and BMI-based general obesity are independently associated with respiratory symptoms, early- and late-onset asthma, COPD, chronic bronchitis, rhinitis, and sex, Marta A. Kisiel, MD, PhD, of the department of environmental and occupational medicine, Uppsala University, Sweden, and colleagues write.

In a prospective study published in the journal Respiratory Medicine, the researchers report on a cross-sectional investigation of responses to a questionnaire similar to one utilized 10 years earlier in the RHINE II study. Questions required simple yes/no responses that covered asthma, respiratory symptoms, allergic rhinitis, chronic bronchitis, and COPD. Additional requested information included age of asthma onset, potential confounding variables of age, smoking, physical activity, and highest education level, weight and height for BMI calculation, and WC measurement with instructions and a provided tape measure.

The population of the RHINE III study conducted from 2010 to 2012 was composed of 12,290 participants (53% response frequency) obtained from a total of seven research centers located in five northern European countries. Obesity categorization classified 1,837 (6.7%) participants as generally obese based on a high BMI ≥ 30 kg/m² and 4,261 (34.7%) as abdominally obese by WC measurements of ≥ 102 cm for men and ≥ 88 cm for women. Of the 4,261 total participants, 1,669 met both general and abdominal obesity criteria. Mean age was in the low 50s range and the obese population consisted of more women than men.

Simple linear regression revealed that BMI and WC were highly correlated, and both were associated with tested respiratory conditions when adjusted for confounding variables. Differences with respect to WC and BMI were independently associated with most of the examined respiratory conditions when WC was adjusted for BMI and vice versa. Neither early-onset asthma nor allergic rhinitis were associated with WC, BMI, or abdominal or general obesity.

A significantly high proportion of individuals with general and abdominal obesity experienced a variety of defined respiratory symptoms, and asthma, chronic bronchitis, or COPD. An independent association of abdominal obesity (with or without general obesity) was found to occur with respiratory symptoms, asthma, late-onset asthma, and chronic bronchitis.

After adjusting for abdominal obesity, general obesity showed an independent and significant association with respiratory symptoms, asthma, adult-onset asthma, and COPD. An analysis stratified by sex indicated a significant association of abdominal and general obesity with asthma in women presented as an odds ratio of 1.56 (95% confidence interval, 1.30-1.87) and 1.95 (95% CI, 1.56-2.43), respectively, compared with men, with an OR of 1.22 (95% CI, 0.97-3.17) and 1.28 (95% CI, 0.97-1.68), respectively. The association of abdominal and general obesity with COPD was also stronger in women, compared with men.

The researchers conclude that “both general and abdominal obesity [were], independent of each other, associated with respiratory symptoms in adults.” There is also a distinct difference between women and men for the association of self-reported asthma and COPD with abdominal and general obesity.

The large randomly selected sample size of participants from research centers located in five northern European countries was considered a major strength of this study as it permitted simultaneous adjustment for multiple potential confounders. Several limitations were acknowledged, including absence of data on obstructive respiratory disease severity, WC measurements not being performed by trained staff, and self-reported height and weight measurements.

The authors have disclosed no relevant financial relationships.

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

A recent Swedish study found that both abdominal and general obesity were independently associated with respiratory illnesses, including asthma and self-reported chronic obstructive pulmonary disease.

Relationships between respiratory conditions with characterized obesity types in adults were assessed using self-report surveys from participants originally enrolled in the European Community Respiratory Health Survey (ECRHS) investigating asthma, allergy, and risk factors. The Respiratory Health in Northern Europe (RHINE) III provides a second follow-up substudy of ECRHS focused on two forms of obesity associated with respiratory illnesses.

Obesity is a characteristic risk factor linked to respiratory ailments such as asthma and COPD. High body mass index (BMI) and waist circumference (WC) provide quantitative measurements for defining conditions of comprehensive general and abdominal obesity, respectively.

Although both types of obesity have been associated with asthma incidence, studies on their independent impact on this disease have been limited. Previous reports on abdominal obesity associated with asthma have been inconsistent when considering sexes in the analysis. Additionally, COPD and related outcomes differed between abdominal and general obesity, indicating a need to discover whether self-reported WC abdominal obesity and BMI-based general obesity are independently associated with respiratory symptoms, early- and late-onset asthma, COPD, chronic bronchitis, rhinitis, and sex, Marta A. Kisiel, MD, PhD, of the department of environmental and occupational medicine, Uppsala University, Sweden, and colleagues write.

In a prospective study published in the journal Respiratory Medicine, the researchers report on a cross-sectional investigation of responses to a questionnaire similar to one utilized 10 years earlier in the RHINE II study. Questions required simple yes/no responses that covered asthma, respiratory symptoms, allergic rhinitis, chronic bronchitis, and COPD. Additional requested information included age of asthma onset, potential confounding variables of age, smoking, physical activity, and highest education level, weight and height for BMI calculation, and WC measurement with instructions and a provided tape measure.

The population of the RHINE III study conducted from 2010 to 2012 was composed of 12,290 participants (53% response frequency) obtained from a total of seven research centers located in five northern European countries. Obesity categorization classified 1,837 (6.7%) participants as generally obese based on a high BMI ≥ 30 kg/m² and 4,261 (34.7%) as abdominally obese by WC measurements of ≥ 102 cm for men and ≥ 88 cm for women. Of the 4,261 total participants, 1,669 met both general and abdominal obesity criteria. Mean age was in the low 50s range and the obese population consisted of more women than men.

Simple linear regression revealed that BMI and WC were highly correlated, and both were associated with tested respiratory conditions when adjusted for confounding variables. Differences with respect to WC and BMI were independently associated with most of the examined respiratory conditions when WC was adjusted for BMI and vice versa. Neither early-onset asthma nor allergic rhinitis were associated with WC, BMI, or abdominal or general obesity.

A significantly high proportion of individuals with general and abdominal obesity experienced a variety of defined respiratory symptoms, and asthma, chronic bronchitis, or COPD. An independent association of abdominal obesity (with or without general obesity) was found to occur with respiratory symptoms, asthma, late-onset asthma, and chronic bronchitis.

After adjusting for abdominal obesity, general obesity showed an independent and significant association with respiratory symptoms, asthma, adult-onset asthma, and COPD. An analysis stratified by sex indicated a significant association of abdominal and general obesity with asthma in women presented as an odds ratio of 1.56 (95% confidence interval, 1.30-1.87) and 1.95 (95% CI, 1.56-2.43), respectively, compared with men, with an OR of 1.22 (95% CI, 0.97-3.17) and 1.28 (95% CI, 0.97-1.68), respectively. The association of abdominal and general obesity with COPD was also stronger in women, compared with men.

The researchers conclude that “both general and abdominal obesity [were], independent of each other, associated with respiratory symptoms in adults.” There is also a distinct difference between women and men for the association of self-reported asthma and COPD with abdominal and general obesity.

The large randomly selected sample size of participants from research centers located in five northern European countries was considered a major strength of this study as it permitted simultaneous adjustment for multiple potential confounders. Several limitations were acknowledged, including absence of data on obstructive respiratory disease severity, WC measurements not being performed by trained staff, and self-reported height and weight measurements.

The authors have disclosed no relevant financial relationships.

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

Dysphagia treatment may be a way to reduce risk for chronic obstructive pulmonary disease (COPD) exacerbations, according to Yoshitaka Oku, MD, of Hyogo Medical University, Nishinomiya, Japan.

Gastroesophageal regurgitation disease (GERD) is known to be associated with exacerbations in COPD, but previous studies have shown little impact of standard GERD therapy on COPD exacerbations. However, additional research indicates that delayed swallowing contributes to COPD exacerbations, as reported in a research review.

In an article published recently in Respiratory Physiology & Neurobiology, Dr. Oku hypothesized that swallowing abnormalities are a confounding factor in the association between GERD and COPD exacerbation, and that counteracting swallowing disorders may reduce COPD exacerbations.

Swallowing disorder (dysphagia) is a common comorbidity in patients with COPD and has been reported at a 17%-20% greater prevalence in those with COPD, compared with controls, the researchers said.

Patients with COPD have altered swallowing behavior because of several factors, including decreased maximal laryngeal elevation, Dr. Oku said. Individuals with COPD “are also prone to laryngeal penetration and aspiration when swallowing large volumes of liquid and tend to follow an inspiratory-swallow-expiratory (I-SW-E) pattern when swallowing large volumes,” he explained.

Dr. Oku conducted prospective studies to investigate the impact of breathing-swallowing discoordination on COPD exacerbation. He found that discoordination in swallowing patterns and the inability to produce airway protective mechanism (such as the I-SW-E pattern) may contribute to more frequent aspirations and more frequent exacerbations.

Dr. Oku also examined whether CPAP and bilevel positive airway pressure (BiPAP) might affect breathing-swallowing coordination in healthy controls and patients with COPD. They found a decrease in breathing-swallowing coordination with CPAP, but not BiPAP, in both controls and stable COPD patients. “During BiPAP, a brief negative flow associated with relaxation of the pharyngeal constrictor muscle triggers inspiratory support, which results in the SW-I pattern,” Dr. Oku noted.

Dr. Oku also wrote that interferential current stimulation (IFC) has been used to stimulate muscles. Studies of transcutaneous electrical sensory stimulation using IFC (IFC-TESS) as an intervention to improve swallowing have shown some success, and also may improve airway protection.

“However, its safety and efficacy in patients with COPD remains unknown,” he wrote. Dr. Oku conducted a study of stable COPD patients and found that repeated salivary swallow test (RSST) scores improved significantly after an IFC-TESS intervention.

Breathing-swallowing discoordination may be an early indicator of swallowing disorder in COPD, and interventions can improve these disorders, Dr. Oku added. However, more research is needed to explore whether interventions to improve dysphagia reduce the frequency of exacerbations in COPD patients, he concluded.

The study was supported by a grant from JSPS KAKENHI. Dr. Oku serves as a senior managing director at EuSense Medical Co.

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

Dysphagia treatment may be a way to reduce risk for chronic obstructive pulmonary disease (COPD) exacerbations, according to Yoshitaka Oku, MD, of Hyogo Medical University, Nishinomiya, Japan.

Gastroesophageal regurgitation disease (GERD) is known to be associated with exacerbations in COPD, but previous studies have shown little impact of standard GERD therapy on COPD exacerbations. However, additional research indicates that delayed swallowing contributes to COPD exacerbations, as reported in a research review.

In an article published recently in Respiratory Physiology & Neurobiology, Dr. Oku hypothesized that swallowing abnormalities are a confounding factor in the association between GERD and COPD exacerbation, and that counteracting swallowing disorders may reduce COPD exacerbations.

Swallowing disorder (dysphagia) is a common comorbidity in patients with COPD and has been reported at a 17%-20% greater prevalence in those with COPD, compared with controls, the researchers said.

Patients with COPD have altered swallowing behavior because of several factors, including decreased maximal laryngeal elevation, Dr. Oku said. Individuals with COPD “are also prone to laryngeal penetration and aspiration when swallowing large volumes of liquid and tend to follow an inspiratory-swallow-expiratory (I-SW-E) pattern when swallowing large volumes,” he explained.

Dr. Oku conducted prospective studies to investigate the impact of breathing-swallowing discoordination on COPD exacerbation. He found that discoordination in swallowing patterns and the inability to produce airway protective mechanism (such as the I-SW-E pattern) may contribute to more frequent aspirations and more frequent exacerbations.

Dr. Oku also examined whether CPAP and bilevel positive airway pressure (BiPAP) might affect breathing-swallowing coordination in healthy controls and patients with COPD. They found a decrease in breathing-swallowing coordination with CPAP, but not BiPAP, in both controls and stable COPD patients. “During BiPAP, a brief negative flow associated with relaxation of the pharyngeal constrictor muscle triggers inspiratory support, which results in the SW-I pattern,” Dr. Oku noted.

Dr. Oku also wrote that interferential current stimulation (IFC) has been used to stimulate muscles. Studies of transcutaneous electrical sensory stimulation using IFC (IFC-TESS) as an intervention to improve swallowing have shown some success, and also may improve airway protection.

“However, its safety and efficacy in patients with COPD remains unknown,” he wrote. Dr. Oku conducted a study of stable COPD patients and found that repeated salivary swallow test (RSST) scores improved significantly after an IFC-TESS intervention.

Breathing-swallowing discoordination may be an early indicator of swallowing disorder in COPD, and interventions can improve these disorders, Dr. Oku added. However, more research is needed to explore whether interventions to improve dysphagia reduce the frequency of exacerbations in COPD patients, he concluded.

The study was supported by a grant from JSPS KAKENHI. Dr. Oku serves as a senior managing director at EuSense Medical Co.

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

Dysphagia treatment may be a way to reduce risk for chronic obstructive pulmonary disease (COPD) exacerbations, according to Yoshitaka Oku, MD, of Hyogo Medical University, Nishinomiya, Japan.

Gastroesophageal regurgitation disease (GERD) is known to be associated with exacerbations in COPD, but previous studies have shown little impact of standard GERD therapy on COPD exacerbations. However, additional research indicates that delayed swallowing contributes to COPD exacerbations, as reported in a research review.

In an article published recently in Respiratory Physiology & Neurobiology, Dr. Oku hypothesized that swallowing abnormalities are a confounding factor in the association between GERD and COPD exacerbation, and that counteracting swallowing disorders may reduce COPD exacerbations.

Swallowing disorder (dysphagia) is a common comorbidity in patients with COPD and has been reported at a 17%-20% greater prevalence in those with COPD, compared with controls, the researchers said.

Patients with COPD have altered swallowing behavior because of several factors, including decreased maximal laryngeal elevation, Dr. Oku said. Individuals with COPD “are also prone to laryngeal penetration and aspiration when swallowing large volumes of liquid and tend to follow an inspiratory-swallow-expiratory (I-SW-E) pattern when swallowing large volumes,” he explained.

Dr. Oku conducted prospective studies to investigate the impact of breathing-swallowing discoordination on COPD exacerbation. He found that discoordination in swallowing patterns and the inability to produce airway protective mechanism (such as the I-SW-E pattern) may contribute to more frequent aspirations and more frequent exacerbations.

Dr. Oku also examined whether CPAP and bilevel positive airway pressure (BiPAP) might affect breathing-swallowing coordination in healthy controls and patients with COPD. They found a decrease in breathing-swallowing coordination with CPAP, but not BiPAP, in both controls and stable COPD patients. “During BiPAP, a brief negative flow associated with relaxation of the pharyngeal constrictor muscle triggers inspiratory support, which results in the SW-I pattern,” Dr. Oku noted.

Dr. Oku also wrote that interferential current stimulation (IFC) has been used to stimulate muscles. Studies of transcutaneous electrical sensory stimulation using IFC (IFC-TESS) as an intervention to improve swallowing have shown some success, and also may improve airway protection.

“However, its safety and efficacy in patients with COPD remains unknown,” he wrote. Dr. Oku conducted a study of stable COPD patients and found that repeated salivary swallow test (RSST) scores improved significantly after an IFC-TESS intervention.

Breathing-swallowing discoordination may be an early indicator of swallowing disorder in COPD, and interventions can improve these disorders, Dr. Oku added. However, more research is needed to explore whether interventions to improve dysphagia reduce the frequency of exacerbations in COPD patients, he concluded.

The study was supported by a grant from JSPS KAKENHI. Dr. Oku serves as a senior managing director at EuSense Medical Co.

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

People with asthma have an elevated risk for a variety of cancers other than lung cancer, including melanoma as well as blood, kidney, and ovarian cancers, new research suggests.

But, the authors found, treatment with an inhaled steroid may lower that risk, perhaps by keeping inflammation in check.

“Using real-world data, our study is the first to provide evidence of a positive association between asthma and cancer risk in United States patients,” Yi Guo, PhD, with the University of Florida, Gainesville, said in a news release.

The study was published online in Cancer Medicine.

The relationship between chronic inflammation and cancer remains a key area of exploration in cancer etiology. Data show that the risk for developing cancer is higher in patients with chronic inflammatory diseases, and patients with asthma have complex and chronic inflammation. However, prior studies exploring a possible link between asthma and cancer have yielded mixed results.

To investigate further, Dr. Guo and colleagues analyzed electronic health records and claims data in the OneFlorida+ clinical research network for roughly 90,000 adults with asthma and a matched cohort of about 270,000 adults without asthma.

Multivariable analysis revealed that adults with asthma were more likely to develop cancer, compared with peers without asthma (hazard ratio, 1.36), the investigators found.

Adults with asthma had an elevated cancer risk for five of the 13 cancers assessed, including melanoma (HR, 1.98), ovarian cancer (HR, 1.88), lung cancer (HR, 1.56), kidney cancer (HR, 1.48), and blood cancer (HR, 1.26).

Compared with adults without asthma, those with asthma who did not treat it with an inhaled steroid had a more pronounced overall cancer risk, compared with those who were on an inhaled steroid (HR, 1.60 vs. 1.11).

For specific cancer types, the risk was elevated for nine of 13 cancers in patients with asthma not taking an inhaled steroid: prostate (HR, 1.50), lung (HR, 1.74), colorectal (HR, 1.51), blood (HR, 1.44), melanoma (HR, 2.05), corpus uteri (HR, 1.76), kidney (HR, 1.52), ovarian (HR, 2.31), and cervical (HR, 1.46).

In contrast, in patients with asthma who did use an inhaled steroid, an elevated cancer risk was observed for only two cancers, lung cancer (HR, 1.39) and melanoma (HR, 1.92), suggesting a potential protective effect of inhaled steroid use on cancer, the researchers said.

Although prior studies have shown a protective effect of inhaled steroid use on some cancers, potentially by reducing inflammation, the “speculative nature of chronic inflammation (asthma as a common example) as a driver for pan-cancer development requires more investigation,” Dr. Guo and colleagues cautioned.

And because of the observational nature of the current study, Dr. Guo’s team stressed that these findings do not prove a causal relationship between asthma and cancer.

“More in-depth studies using real-word data are needed to further explore the causal mechanisms of asthma on cancer risk,” the researchers concluded.

Funding for the study was provided in part by grants to the researchers from the National Institutes of Health, National Cancer Institute, National Institute on Aging, and the Centers for Disease Control and Prevention. This project was supported by the Cancer Informatics Shared Resource in the University of Florida Health Cancer Center. The authors have disclosed no conflicts of interest.

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

People with asthma have an elevated risk for a variety of cancers other than lung cancer, including melanoma as well as blood, kidney, and ovarian cancers, new research suggests.

But, the authors found, treatment with an inhaled steroid may lower that risk, perhaps by keeping inflammation in check.

“Using real-world data, our study is the first to provide evidence of a positive association between asthma and cancer risk in United States patients,” Yi Guo, PhD, with the University of Florida, Gainesville, said in a news release.

The study was published online in Cancer Medicine.

The relationship between chronic inflammation and cancer remains a key area of exploration in cancer etiology. Data show that the risk for developing cancer is higher in patients with chronic inflammatory diseases, and patients with asthma have complex and chronic inflammation. However, prior studies exploring a possible link between asthma and cancer have yielded mixed results.

To investigate further, Dr. Guo and colleagues analyzed electronic health records and claims data in the OneFlorida+ clinical research network for roughly 90,000 adults with asthma and a matched cohort of about 270,000 adults without asthma.

Multivariable analysis revealed that adults with asthma were more likely to develop cancer, compared with peers without asthma (hazard ratio, 1.36), the investigators found.

Adults with asthma had an elevated cancer risk for five of the 13 cancers assessed, including melanoma (HR, 1.98), ovarian cancer (HR, 1.88), lung cancer (HR, 1.56), kidney cancer (HR, 1.48), and blood cancer (HR, 1.26).

Compared with adults without asthma, those with asthma who did not treat it with an inhaled steroid had a more pronounced overall cancer risk, compared with those who were on an inhaled steroid (HR, 1.60 vs. 1.11).

For specific cancer types, the risk was elevated for nine of 13 cancers in patients with asthma not taking an inhaled steroid: prostate (HR, 1.50), lung (HR, 1.74), colorectal (HR, 1.51), blood (HR, 1.44), melanoma (HR, 2.05), corpus uteri (HR, 1.76), kidney (HR, 1.52), ovarian (HR, 2.31), and cervical (HR, 1.46).

In contrast, in patients with asthma who did use an inhaled steroid, an elevated cancer risk was observed for only two cancers, lung cancer (HR, 1.39) and melanoma (HR, 1.92), suggesting a potential protective effect of inhaled steroid use on cancer, the researchers said.

Although prior studies have shown a protective effect of inhaled steroid use on some cancers, potentially by reducing inflammation, the “speculative nature of chronic inflammation (asthma as a common example) as a driver for pan-cancer development requires more investigation,” Dr. Guo and colleagues cautioned.

And because of the observational nature of the current study, Dr. Guo’s team stressed that these findings do not prove a causal relationship between asthma and cancer.

“More in-depth studies using real-word data are needed to further explore the causal mechanisms of asthma on cancer risk,” the researchers concluded.

Funding for the study was provided in part by grants to the researchers from the National Institutes of Health, National Cancer Institute, National Institute on Aging, and the Centers for Disease Control and Prevention. This project was supported by the Cancer Informatics Shared Resource in the University of Florida Health Cancer Center. The authors have disclosed no conflicts of interest.

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

People with asthma have an elevated risk for a variety of cancers other than lung cancer, including melanoma as well as blood, kidney, and ovarian cancers, new research suggests.

But, the authors found, treatment with an inhaled steroid may lower that risk, perhaps by keeping inflammation in check.

“Using real-world data, our study is the first to provide evidence of a positive association between asthma and cancer risk in United States patients,” Yi Guo, PhD, with the University of Florida, Gainesville, said in a news release.

The study was published online in Cancer Medicine.

The relationship between chronic inflammation and cancer remains a key area of exploration in cancer etiology. Data show that the risk for developing cancer is higher in patients with chronic inflammatory diseases, and patients with asthma have complex and chronic inflammation. However, prior studies exploring a possible link between asthma and cancer have yielded mixed results.

To investigate further, Dr. Guo and colleagues analyzed electronic health records and claims data in the OneFlorida+ clinical research network for roughly 90,000 adults with asthma and a matched cohort of about 270,000 adults without asthma.

Multivariable analysis revealed that adults with asthma were more likely to develop cancer, compared with peers without asthma (hazard ratio, 1.36), the investigators found.

Adults with asthma had an elevated cancer risk for five of the 13 cancers assessed, including melanoma (HR, 1.98), ovarian cancer (HR, 1.88), lung cancer (HR, 1.56), kidney cancer (HR, 1.48), and blood cancer (HR, 1.26).

Compared with adults without asthma, those with asthma who did not treat it with an inhaled steroid had a more pronounced overall cancer risk, compared with those who were on an inhaled steroid (HR, 1.60 vs. 1.11).

For specific cancer types, the risk was elevated for nine of 13 cancers in patients with asthma not taking an inhaled steroid: prostate (HR, 1.50), lung (HR, 1.74), colorectal (HR, 1.51), blood (HR, 1.44), melanoma (HR, 2.05), corpus uteri (HR, 1.76), kidney (HR, 1.52), ovarian (HR, 2.31), and cervical (HR, 1.46).

In contrast, in patients with asthma who did use an inhaled steroid, an elevated cancer risk was observed for only two cancers, lung cancer (HR, 1.39) and melanoma (HR, 1.92), suggesting a potential protective effect of inhaled steroid use on cancer, the researchers said.

Although prior studies have shown a protective effect of inhaled steroid use on some cancers, potentially by reducing inflammation, the “speculative nature of chronic inflammation (asthma as a common example) as a driver for pan-cancer development requires more investigation,” Dr. Guo and colleagues cautioned.

And because of the observational nature of the current study, Dr. Guo’s team stressed that these findings do not prove a causal relationship between asthma and cancer.

“More in-depth studies using real-word data are needed to further explore the causal mechanisms of asthma on cancer risk,” the researchers concluded.

Funding for the study was provided in part by grants to the researchers from the National Institutes of Health, National Cancer Institute, National Institute on Aging, and the Centers for Disease Control and Prevention. This project was supported by the Cancer Informatics Shared Resource in the University of Florida Health Cancer Center. The authors have disclosed no conflicts of interest.

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

SAN DIEGO – A COVID-19 combination antiviral is the most important new drug primary care physicians have prescribed in recent years – plus it has helped keep many patients out of the hospital, according to a presenter at the annual meeting of the American College of Physicians.

Nirmatrelvir-ritonavir was granted emergency use authorization by the FDA late in 2021 to prevent progression to severe disease when COVID-19 cases and deaths were surging, and the Delta and Omicron variants started to spread.

Gerald Smetana, MD, an internist at Beth Israel Deaconess Medical Center in Boston, discussed nirmatrelvir-ritonavir as an example of how new drugs relevant to primary care can have a profound impact on public health.
 

Understanding the mechanism of action

Nirmatrelvir is the active agent of this combination and inhibits the SARS-CoV-2 main protease (Mpro), which is required for viral replication. In contrast to the SARS-CoV-2 spike protein, Mpro is highly conserved in coronaviruses and rarely acquires mutations. Therefore, unlike monoclonal antibodies targeting the spike protein, nirmatrelvir is active against known Omicron variants and is predicted to remain active against new variants that may emerge. The HIV1 protease inhibitor ritonavir has no activity against SARS-CoV-2. It can help increase the serum concentration of nirmatrelvir by inhibiting its metabolization.

“Although the details are not important for prescribing internists, having a basic understanding of the mechanism of action can help [doctors] better understand for which patients the drugs are indicated,” said Dr. Smetana, also a professor of medicine at Harvard Medical School, Boston. This is particularly important for newly approved drugs with a lot of new information to digest.

“Knowing the mechanisms of action of new drugs can help us predict their efficacy and potential side effects,” said Hubertus Kiefl, MD, an internist at Beth Israel Deaconess Medical Center and a lecturer at Harvard Medical School, during an interview after the session.

Understanding how drugs work also can help clinicians make better decisions, such as avoiding the use of a monoclonal antibody during a surge of a new variant with mutations in surface proteins or carefully managing the use of nirmatrelvir-ritonavir in patients who take certain medications that would cause potentially serious drug-drug interactions, Dr. Kiefl added.

Nirmatrelvir-ritonavir reduces the risk of hospitalization – but only in high-risk patients.

Dr. Smetana presented published data from the EPIC-HR study, a pivotal phase 2-3 clinical trial in 2,246 adult patients with COVID-19, all of whom were unvaccinated. Additionally, all patients had at least one risk factor for progression to severe disease.

When initiated 5 days after symptom onset or earlier, treatment with 300 mg nirmatrelvir plus 100 mg ritonavir twice a day for 5 days led to an 89% relative risk reduction in COVID-19–related hospitalization or death through day 28, compared with placebo.

Subgroup analyses showed that some patients benefited more than others. The highest risk reduction after treatment with nirmatrelvir-ritonavir was observed in patients at least 65 years old.

“It is important to remember that all the patients of this study were unvaccinated and [had] not had prior SARS-CoV-2 infection. This study population isn’t representative of most patients we are seeing today,” said Dr. Smetana.

Unpublished data from a study of standard-risk patients showed a nonsignificant reduction in the risk of hospitalization or death, he said. The study was stopped because of the low rates of hospitalization and death.
 

Effective in real world, but less so than in clinical trials

The fact that the patient cohort in the EPIC-HR trial was different from the patients internists see today makes real-world data critical for determining the usefulness of nirmatrelvir-ritonavir in everyday practice, Dr. Smetana said.

A real-world study from Israel conducted during the first Omicron wave (January to March 2022) showed that treatment with nirmatrelvir alone substantially reduced the relative risk of hospitalization in adults older than 65, with no evidence of benefit in adults aged 40-65. Dr. Smetana highlighted that, unlike the EPIC-HR cohort, most patients in the Israeli study had prior immunity due to vaccination or prior SARS-CoV-2 infection.
 

Many drug-drug interactions, but they can be managed

Nirmatrelvir-ritonavir interacts with many drugs, some of which are commonly used by primary care patients.

To help internists identify drug-drug interactions, Dr. Smetana proposed the use of the Liverpool COVID-19 Drug Interactions Checker, an intuitive tool that can help prescribers identify potential drug-drug interactions, categorize them based on severity, and identify management strategies.

This tool is specific to COVID-19 drugs. The Liverpool group also offers online drug interaction checkers for HIV, hepatitis, and cancer. “We need more tools like this to help improve the safe use of new drugs,” Dr. Smetana said.

To manage drug interactions, according to Dr. Smetana, U.S. treatment guidelines offer the following three options:

• Prescribe an alternative COVID therapy.
• Temporarily withhold concomitant medication if clinically appropriate.
• Adjust the dose of concomitant medication and monitor for adverse effects.

Medication doses that are withheld or modified should be continued through 3 days after completing nirmatrelvir-ritonavir, he added.
 

Important considerations

Commenting on things to consider for patients with COVID-19, Dr. Smetana said that there is a short window after symptom onset when nirmatrelvir-ritonavir can be prescribed, and safety in pregnancy is not known. There is also uncertainty regarding funding of nirmatrelvir-ritonavir prescriptions after the state of emergency is lifted. He reminded attendees that, although nirmatrelvir-ritonavir is the preferred first-line treatment for high-risk patients, another antiviral agent, molnupiravir, is also available and might be more appropriate for some patients.

He also cautioned about prescribing new drugs off label for indications that are not yet FDA-approved. “We are often stewards of limited resources when new drugs first become available but are not yet in sufficient supply to meet demand. Limiting our prescribing to FDA-approved indications helps to ensure equitable access,” he said.

Dr. Smetana and Dr. Kiefl reported no disclosures.

SAN DIEGO – A COVID-19 combination antiviral is the most important new drug primary care physicians have prescribed in recent years – plus it has helped keep many patients out of the hospital, according to a presenter at the annual meeting of the American College of Physicians.

Nirmatrelvir-ritonavir was granted emergency use authorization by the FDA late in 2021 to prevent progression to severe disease when COVID-19 cases and deaths were surging, and the Delta and Omicron variants started to spread.

Gerald Smetana, MD, an internist at Beth Israel Deaconess Medical Center in Boston, discussed nirmatrelvir-ritonavir as an example of how new drugs relevant to primary care can have a profound impact on public health.
 

Understanding the mechanism of action

Nirmatrelvir is the active agent of this combination and inhibits the SARS-CoV-2 main protease (Mpro), which is required for viral replication. In contrast to the SARS-CoV-2 spike protein, Mpro is highly conserved in coronaviruses and rarely acquires mutations. Therefore, unlike monoclonal antibodies targeting the spike protein, nirmatrelvir is active against known Omicron variants and is predicted to remain active against new variants that may emerge. The HIV1 protease inhibitor ritonavir has no activity against SARS-CoV-2. It can help increase the serum concentration of nirmatrelvir by inhibiting its metabolization.

“Although the details are not important for prescribing internists, having a basic understanding of the mechanism of action can help [doctors] better understand for which patients the drugs are indicated,” said Dr. Smetana, also a professor of medicine at Harvard Medical School, Boston. This is particularly important for newly approved drugs with a lot of new information to digest.

“Knowing the mechanisms of action of new drugs can help us predict their efficacy and potential side effects,” said Hubertus Kiefl, MD, an internist at Beth Israel Deaconess Medical Center and a lecturer at Harvard Medical School, during an interview after the session.

Understanding how drugs work also can help clinicians make better decisions, such as avoiding the use of a monoclonal antibody during a surge of a new variant with mutations in surface proteins or carefully managing the use of nirmatrelvir-ritonavir in patients who take certain medications that would cause potentially serious drug-drug interactions, Dr. Kiefl added.

Nirmatrelvir-ritonavir reduces the risk of hospitalization – but only in high-risk patients.

Dr. Smetana presented published data from the EPIC-HR study, a pivotal phase 2-3 clinical trial in 2,246 adult patients with COVID-19, all of whom were unvaccinated. Additionally, all patients had at least one risk factor for progression to severe disease.

When initiated 5 days after symptom onset or earlier, treatment with 300 mg nirmatrelvir plus 100 mg ritonavir twice a day for 5 days led to an 89% relative risk reduction in COVID-19–related hospitalization or death through day 28, compared with placebo.

Subgroup analyses showed that some patients benefited more than others. The highest risk reduction after treatment with nirmatrelvir-ritonavir was observed in patients at least 65 years old.

“It is important to remember that all the patients of this study were unvaccinated and [had] not had prior SARS-CoV-2 infection. This study population isn’t representative of most patients we are seeing today,” said Dr. Smetana.

Unpublished data from a study of standard-risk patients showed a nonsignificant reduction in the risk of hospitalization or death, he said. The study was stopped because of the low rates of hospitalization and death.
 

Effective in real world, but less so than in clinical trials

The fact that the patient cohort in the EPIC-HR trial was different from the patients internists see today makes real-world data critical for determining the usefulness of nirmatrelvir-ritonavir in everyday practice, Dr. Smetana said.

A real-world study from Israel conducted during the first Omicron wave (January to March 2022) showed that treatment with nirmatrelvir alone substantially reduced the relative risk of hospitalization in adults older than 65, with no evidence of benefit in adults aged 40-65. Dr. Smetana highlighted that, unlike the EPIC-HR cohort, most patients in the Israeli study had prior immunity due to vaccination or prior SARS-CoV-2 infection.
 

Many drug-drug interactions, but they can be managed

Nirmatrelvir-ritonavir interacts with many drugs, some of which are commonly used by primary care patients.

To help internists identify drug-drug interactions, Dr. Smetana proposed the use of the Liverpool COVID-19 Drug Interactions Checker, an intuitive tool that can help prescribers identify potential drug-drug interactions, categorize them based on severity, and identify management strategies.

This tool is specific to COVID-19 drugs. The Liverpool group also offers online drug interaction checkers for HIV, hepatitis, and cancer. “We need more tools like this to help improve the safe use of new drugs,” Dr. Smetana said.

To manage drug interactions, according to Dr. Smetana, U.S. treatment guidelines offer the following three options:

• Prescribe an alternative COVID therapy.
• Temporarily withhold concomitant medication if clinically appropriate.
• Adjust the dose of concomitant medication and monitor for adverse effects.

Medication doses that are withheld or modified should be continued through 3 days after completing nirmatrelvir-ritonavir, he added.
 

Important considerations

Commenting on things to consider for patients with COVID-19, Dr. Smetana said that there is a short window after symptom onset when nirmatrelvir-ritonavir can be prescribed, and safety in pregnancy is not known. There is also uncertainty regarding funding of nirmatrelvir-ritonavir prescriptions after the state of emergency is lifted. He reminded attendees that, although nirmatrelvir-ritonavir is the preferred first-line treatment for high-risk patients, another antiviral agent, molnupiravir, is also available and might be more appropriate for some patients.

He also cautioned about prescribing new drugs off label for indications that are not yet FDA-approved. “We are often stewards of limited resources when new drugs first become available but are not yet in sufficient supply to meet demand. Limiting our prescribing to FDA-approved indications helps to ensure equitable access,” he said.

Dr. Smetana and Dr. Kiefl reported no disclosures.

SAN DIEGO – A COVID-19 combination antiviral is the most important new drug primary care physicians have prescribed in recent years – plus it has helped keep many patients out of the hospital, according to a presenter at the annual meeting of the American College of Physicians.

Nirmatrelvir-ritonavir was granted emergency use authorization by the FDA late in 2021 to prevent progression to severe disease when COVID-19 cases and deaths were surging, and the Delta and Omicron variants started to spread.

Gerald Smetana, MD, an internist at Beth Israel Deaconess Medical Center in Boston, discussed nirmatrelvir-ritonavir as an example of how new drugs relevant to primary care can have a profound impact on public health.
 

Understanding the mechanism of action

Nirmatrelvir is the active agent of this combination and inhibits the SARS-CoV-2 main protease (Mpro), which is required for viral replication. In contrast to the SARS-CoV-2 spike protein, Mpro is highly conserved in coronaviruses and rarely acquires mutations. Therefore, unlike monoclonal antibodies targeting the spike protein, nirmatrelvir is active against known Omicron variants and is predicted to remain active against new variants that may emerge. The HIV1 protease inhibitor ritonavir has no activity against SARS-CoV-2. It can help increase the serum concentration of nirmatrelvir by inhibiting its metabolization.

“Although the details are not important for prescribing internists, having a basic understanding of the mechanism of action can help [doctors] better understand for which patients the drugs are indicated,” said Dr. Smetana, also a professor of medicine at Harvard Medical School, Boston. This is particularly important for newly approved drugs with a lot of new information to digest.

“Knowing the mechanisms of action of new drugs can help us predict their efficacy and potential side effects,” said Hubertus Kiefl, MD, an internist at Beth Israel Deaconess Medical Center and a lecturer at Harvard Medical School, during an interview after the session.

Understanding how drugs work also can help clinicians make better decisions, such as avoiding the use of a monoclonal antibody during a surge of a new variant with mutations in surface proteins or carefully managing the use of nirmatrelvir-ritonavir in patients who take certain medications that would cause potentially serious drug-drug interactions, Dr. Kiefl added.

Nirmatrelvir-ritonavir reduces the risk of hospitalization – but only in high-risk patients.

Dr. Smetana presented published data from the EPIC-HR study, a pivotal phase 2-3 clinical trial in 2,246 adult patients with COVID-19, all of whom were unvaccinated. Additionally, all patients had at least one risk factor for progression to severe disease.

When initiated 5 days after symptom onset or earlier, treatment with 300 mg nirmatrelvir plus 100 mg ritonavir twice a day for 5 days led to an 89% relative risk reduction in COVID-19–related hospitalization or death through day 28, compared with placebo.

Subgroup analyses showed that some patients benefited more than others. The highest risk reduction after treatment with nirmatrelvir-ritonavir was observed in patients at least 65 years old.

“It is important to remember that all the patients of this study were unvaccinated and [had] not had prior SARS-CoV-2 infection. This study population isn’t representative of most patients we are seeing today,” said Dr. Smetana.

Unpublished data from a study of standard-risk patients showed a nonsignificant reduction in the risk of hospitalization or death, he said. The study was stopped because of the low rates of hospitalization and death.
 

Effective in real world, but less so than in clinical trials

The fact that the patient cohort in the EPIC-HR trial was different from the patients internists see today makes real-world data critical for determining the usefulness of nirmatrelvir-ritonavir in everyday practice, Dr. Smetana said.

A real-world study from Israel conducted during the first Omicron wave (January to March 2022) showed that treatment with nirmatrelvir alone substantially reduced the relative risk of hospitalization in adults older than 65, with no evidence of benefit in adults aged 40-65. Dr. Smetana highlighted that, unlike the EPIC-HR cohort, most patients in the Israeli study had prior immunity due to vaccination or prior SARS-CoV-2 infection.
 

Many drug-drug interactions, but they can be managed

Nirmatrelvir-ritonavir interacts with many drugs, some of which are commonly used by primary care patients.

To help internists identify drug-drug interactions, Dr. Smetana proposed the use of the Liverpool COVID-19 Drug Interactions Checker, an intuitive tool that can help prescribers identify potential drug-drug interactions, categorize them based on severity, and identify management strategies.

This tool is specific to COVID-19 drugs. The Liverpool group also offers online drug interaction checkers for HIV, hepatitis, and cancer. “We need more tools like this to help improve the safe use of new drugs,” Dr. Smetana said.

To manage drug interactions, according to Dr. Smetana, U.S. treatment guidelines offer the following three options:

• Prescribe an alternative COVID therapy.
• Temporarily withhold concomitant medication if clinically appropriate.
• Adjust the dose of concomitant medication and monitor for adverse effects.

Medication doses that are withheld or modified should be continued through 3 days after completing nirmatrelvir-ritonavir, he added.
 

Important considerations

Commenting on things to consider for patients with COVID-19, Dr. Smetana said that there is a short window after symptom onset when nirmatrelvir-ritonavir can be prescribed, and safety in pregnancy is not known. There is also uncertainty regarding funding of nirmatrelvir-ritonavir prescriptions after the state of emergency is lifted. He reminded attendees that, although nirmatrelvir-ritonavir is the preferred first-line treatment for high-risk patients, another antiviral agent, molnupiravir, is also available and might be more appropriate for some patients.

He also cautioned about prescribing new drugs off label for indications that are not yet FDA-approved. “We are often stewards of limited resources when new drugs first become available but are not yet in sufficient supply to meet demand. Limiting our prescribing to FDA-approved indications helps to ensure equitable access,” he said.

Dr. Smetana and Dr. Kiefl reported no disclosures.

Rashelle Bernal vaped and ended up in an induced coma for a week. She was one of almost 3,000 people who were hospitalized during 2019 and early 2020 with severe lung damage from vaping and became part of what is now known as the epidemic of e-cigarette, or vaping, product use–associated lung injury (EVALI).

For many, the EVALI epidemic is a distant, pre-COVID memory.

But the vaping-related injuries are still happening. And for Ms. Bernal, the aftermath is her reality. Her pulmonologist from that time described the harm from the vape ingredients as an oil spill in her lungs. Eventually, the toxins would probably clear. But she will likely wrestle with the injuries for a very long time.

More than 3 years later, she frequently finds herself in the emergency department.

“If I get sick, if there’s anything that irritates my lungs – it could be something as simple as pollen in the air – it will cause me to get like a bacterial infection or other issues, and I can’t breathe,” Ms. Ms. Bernal, now 30, said in a recent interview. “I get really winded, to the point where I’ll walk up the stairs and I feel like I just ran a mile.”

In 2019 and 2020, a media firestorm erupted as hospitals notified the public of outbreaks of vaping-related lung injuries. News headlines reported e-cigarettes were killing teens from Texas to the Bronx. Investigators at the U.S. Centers for Disease Control and Prevention tracked most of the cases to vitamin E acetate, an additive in illicit cannabis vaping products intended to promote the metabolism of tetrahydrocannabinol (THC). The agency stopped tracking EVALI in February 2020.

But 2 months later, in April 2020, the agency’s National Center for Health Statistics implemented a diagnostic code, U07.0, for health care professionals in the United States to diagnose EVALI for the first time. The code is also used for lung damage related to use of electronic cigarettes and “dabbing” – a method of inhaling cannabis. Damage could include inflammation of the lungs, pulmonary hemorrhage, and eosinophilic pneumonia.

The incidence of these diagnoses appears to have risen sharply since 2020. In the last three months of 2020, a total of 11,300 medical claims included the U07.0 code. That figure rose to 22,000 in 2021 and hit 31,600 in 2022, according to data compiled for and provided to Medscape by Komodo Health, a health care technology company that holds a database of more than 330 million U.S. patients from Medicare, Medicaid, and commercial insurers’ medical, pharmacy, and laboratory claims.

Harm from vaping, including EVALI, has continued.

“We’re still seeing a number of patients diagnosed with vaping disorders, but it’s not top of mind,” said Usha Periyanayagam, MD, MPH, head of clinic product and real-world evidence for Komodo and a former emergency medicine physician.
 

Where it started

Devika Rao, MD, a pediatric pulmonology specialist at UT Southwestern Medical Center, Dallas, has cared for most of her EVALI patients in the hospital, with the most recent case in early 2023. But in January, for the first time, she saw an EVALI patient in an outpatient clinic. The person had not been admitted to the hospital – like most were pre-pandemic. And like most who were seen during the pandemic, this patient had milder symptoms, not requiring intubation or take-home oxygen.

In 2019 and the beginning of 2020, many EVALI patients who were eventually hospitalized first sought help at urgent care centers or with primary care doctors and were presumed to have pneumonia or gastroenteritis and sent home.

“But they got worse, and they would present to our emergency room; their chest X-rays and CT scans showed extensive lung disease,” Dr. Rao said, adding that the damage was striking among patients all under age 18. “They were short of breath. Their oxygen levels were low. They had diminished lung function. And they had a lot of GI issues like abdominal pain and weight loss from nausea and vomiting.”

“These overwhelming inflammatory reactions that we see with EVALI,” said Karen M. Wilson, MD, MPH, a pediatric hospitalist at the University of Rochester (N.Y.) Medical Center and a tobacco use researcher. “You might find some microvascular changes with normal inhaling of smoke or aerosol, but you’re not going to find macro changes like we see with the EVALI.”

In late 2019, images of the CT scans of patients with EVALI were published, grabbing the attention of Arun Kannappan, MD, an assistant professor of pulmonary sciences and critical care at the University of Colorado Anschutz School of Medicine, Aurora. Dr. Kannappan knew a patient with such severe lung damage could develop acute respiratory distress syndrome, which means a patient would be put on a ventilator because their inflamed lungs could not oxygenate blood.

“That confers within somewhere between 30% to 50% chance of dying; it made all of the pulmonary specialists really turn their heads to make sure that we keep a lookout for it,” said Dr. Kannappan.

CT scans of lungs proved to be a critical diagnostic tool for doctors. Most of the images from patients showed acute inflammation and diffuse lung damage. Ehab Ali, MD, a critical care and pulmonary disease medicine specialist in Louisville, Ky., said the damage was often spread across both lungs in many areas and appeared opaque and hazy, known as “ground glass.” COVID-19, meanwhile, appeared differently in lung scans, often with damage that was more isolated.

But many diseases carry a “ground glass” appearance, with many potential causes, like infections, cigarette smoke, or an autoimmune condition.

“Before you even talk to the patient, you can immediately put it in your mind that ‘I’m going to ask this patient if they vape,’ when I see the distribution of ground glass appearance,” Dr. Ali said.

Dr. Ali said other factors, like the age of the patient – about three-quarters of EVALI patients are under age 34, according to the CDC – would spur him to ask about vaping. But because so many patients were young, discerning vape usage wasn’t always easy.  

“When you’re talking to teenagers, if you ask them upon admission, with the parents in the room, they’re going say ‘no,’ ” said Rachel Boykan, MD, a pediatric hospitalist at Stony Brook (N.Y.) Children’s. She added that her hospital is still seeing cases.

Dr. Rao said it often takes two to three people asking a patient about any vape usage before they confess.

Ms. Bernal, who was 27 at the time of her hospital admission for EVALI, said she bought vapes with THC at a retail shop in California. She’d been a traditional marijuana smoker, using the leaf product, but switched when someone told her it was healthier to vape THC than inhale smoke from burned marijuana leaves into her lungs. “I thought this was safe.”

Dr. Rao and her colleagues recently published a study of 41 teenage patients with EVALI who were seen at Children’s Medical Center Dallas between December 2018 and July 2021. All but one reported using e-cigarettes containing THC, and the CDC in its most recent report from February 2020 said about 80% of patients had used vapes containing THC.

The CDC also found that vitamin E acetate, an oily substance that allows THC to travel from the lungs to the brain quickly and an ingredient used in the food and cosmetics industries, was found in many of the lungs of EVALI patients, though not all.
 

The aftermath

The outcomes of the thousands of patients who had EVALI – and those who may still be developing it – are largely untracked.

Bonnie Halpern-Felsher, PhD, director at the Stanford (Calif.) Reach Lab that bears her name and a researcher on tobacco in youth, said she and many of her colleagues are frustrated that the CDC is not continuing to collect data on EVALI.

“I know a lot of colleagues who’ve said that they’re still seeing EVALI, but because of COVID-19 they stopped collecting the data. And that’s been very frustrating because it’s hard to say whether the kinds of lung issues you’re having are related to e-cigarettes, generally, or EVALI,” Dr. Halpern-Felsher said.

Researchers and doctors affiliated with the American Thoracic Society published a report with solutions on how to better track EVALI. They recommended that a national case registry and biorepository be created.

Doctors also worry that many cases were missed. Dr. Boykan said that while protocol dictated nurses and other clinicians ask about a history of vaping – a key part of EVALI diagnosis – many did not. Dr. Ali, the Louisville critical care physician, said EVALI symptoms of nausea, cough, and fever are associated with viral infections.

“I’m sure that some of these cases might be discharged from the emergency room as a virus,” Dr. Ali said. “Most of the time patients would get prescribed steroids for viral infections, which may help EVALI patients even though it’s never been studied.”

Dr. Rao also said the treatment regimen at Children’s MC Dallas, which included high doses of intravenous steroids, seemed to help. But the best management approach for treatment, or long-term follow up care, has not been studied.

The report in the Annals of the American Thoracic Society said prospective studies are showing that a significant portion of patients with EVALI experience prolonged respiratory issues and cognitive and mood impairment. Dr. Rao said a common thread for many of her EVALI patients has been significant stress in their lives with school or family, which led them to vape in an attempt to reduce stress.

That was certainly the case for Ms. Bernal before her hospital admission. She had recently moved across the country for her husband’s job, was trying to buy a house, and had spent months in a hotel with three children. She vaped to cope.

But she said her mental and cognitive health has worsened. Back in Louisville, she saw a neurologist, who told her that her brain had shrunk, she said. She hasn’t found a new neurologist in Portland, Ore., where her family moved a year after the EVALI episode.

But she often finds herself overwhelmed and overstimulated with tasks that she said she never had problems with before. She tears up while talking about the newfound limitations. She struggled to find a primary care physician who could medically manage her mental health and a counselor who can understand what she’s been through with EVALI.

But, “a lot of doctors aren’t educated in it, and they don’t know how to respond or they don’t know what to do,” Ms. Bernal said. “And that makes me feel like, I guess, what I had wasn’t important.”

Ms. Bernal does have a new pulmonologist and is going in for a round of pulmonary tests soon because she often finds herself unable to breathe while completing simple tasks. She is tired of rushing to the ER. She wants answers, or some kind of treatment to help her feel normal again.

“I feel like this is my fault,” Ms. Bernal said. “Had I not smoked, I would be fine, and that’s hard to live with. Every day. Telling yourself, ‘It’s your fault.’ It’s been how many years now? And I still haven’t found peace yet. I don’t know if ever will.”

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

Rashelle Bernal vaped and ended up in an induced coma for a week. She was one of almost 3,000 people who were hospitalized during 2019 and early 2020 with severe lung damage from vaping and became part of what is now known as the epidemic of e-cigarette, or vaping, product use–associated lung injury (EVALI).

For many, the EVALI epidemic is a distant, pre-COVID memory.

But the vaping-related injuries are still happening. And for Ms. Bernal, the aftermath is her reality. Her pulmonologist from that time described the harm from the vape ingredients as an oil spill in her lungs. Eventually, the toxins would probably clear. But she will likely wrestle with the injuries for a very long time.

More than 3 years later, she frequently finds herself in the emergency department.

“If I get sick, if there’s anything that irritates my lungs – it could be something as simple as pollen in the air – it will cause me to get like a bacterial infection or other issues, and I can’t breathe,” Ms. Ms. Bernal, now 30, said in a recent interview. “I get really winded, to the point where I’ll walk up the stairs and I feel like I just ran a mile.”

In 2019 and 2020, a media firestorm erupted as hospitals notified the public of outbreaks of vaping-related lung injuries. News headlines reported e-cigarettes were killing teens from Texas to the Bronx. Investigators at the U.S. Centers for Disease Control and Prevention tracked most of the cases to vitamin E acetate, an additive in illicit cannabis vaping products intended to promote the metabolism of tetrahydrocannabinol (THC). The agency stopped tracking EVALI in February 2020.

But 2 months later, in April 2020, the agency’s National Center for Health Statistics implemented a diagnostic code, U07.0, for health care professionals in the United States to diagnose EVALI for the first time. The code is also used for lung damage related to use of electronic cigarettes and “dabbing” – a method of inhaling cannabis. Damage could include inflammation of the lungs, pulmonary hemorrhage, and eosinophilic pneumonia.

The incidence of these diagnoses appears to have risen sharply since 2020. In the last three months of 2020, a total of 11,300 medical claims included the U07.0 code. That figure rose to 22,000 in 2021 and hit 31,600 in 2022, according to data compiled for and provided to Medscape by Komodo Health, a health care technology company that holds a database of more than 330 million U.S. patients from Medicare, Medicaid, and commercial insurers’ medical, pharmacy, and laboratory claims.

Harm from vaping, including EVALI, has continued.

“We’re still seeing a number of patients diagnosed with vaping disorders, but it’s not top of mind,” said Usha Periyanayagam, MD, MPH, head of clinic product and real-world evidence for Komodo and a former emergency medicine physician.
 

Where it started

Devika Rao, MD, a pediatric pulmonology specialist at UT Southwestern Medical Center, Dallas, has cared for most of her EVALI patients in the hospital, with the most recent case in early 2023. But in January, for the first time, she saw an EVALI patient in an outpatient clinic. The person had not been admitted to the hospital – like most were pre-pandemic. And like most who were seen during the pandemic, this patient had milder symptoms, not requiring intubation or take-home oxygen.

In 2019 and the beginning of 2020, many EVALI patients who were eventually hospitalized first sought help at urgent care centers or with primary care doctors and were presumed to have pneumonia or gastroenteritis and sent home.

“But they got worse, and they would present to our emergency room; their chest X-rays and CT scans showed extensive lung disease,” Dr. Rao said, adding that the damage was striking among patients all under age 18. “They were short of breath. Their oxygen levels were low. They had diminished lung function. And they had a lot of GI issues like abdominal pain and weight loss from nausea and vomiting.”

“These overwhelming inflammatory reactions that we see with EVALI,” said Karen M. Wilson, MD, MPH, a pediatric hospitalist at the University of Rochester (N.Y.) Medical Center and a tobacco use researcher. “You might find some microvascular changes with normal inhaling of smoke or aerosol, but you’re not going to find macro changes like we see with the EVALI.”

In late 2019, images of the CT scans of patients with EVALI were published, grabbing the attention of Arun Kannappan, MD, an assistant professor of pulmonary sciences and critical care at the University of Colorado Anschutz School of Medicine, Aurora. Dr. Kannappan knew a patient with such severe lung damage could develop acute respiratory distress syndrome, which means a patient would be put on a ventilator because their inflamed lungs could not oxygenate blood.

“That confers within somewhere between 30% to 50% chance of dying; it made all of the pulmonary specialists really turn their heads to make sure that we keep a lookout for it,” said Dr. Kannappan.

CT scans of lungs proved to be a critical diagnostic tool for doctors. Most of the images from patients showed acute inflammation and diffuse lung damage. Ehab Ali, MD, a critical care and pulmonary disease medicine specialist in Louisville, Ky., said the damage was often spread across both lungs in many areas and appeared opaque and hazy, known as “ground glass.” COVID-19, meanwhile, appeared differently in lung scans, often with damage that was more isolated.

But many diseases carry a “ground glass” appearance, with many potential causes, like infections, cigarette smoke, or an autoimmune condition.

“Before you even talk to the patient, you can immediately put it in your mind that ‘I’m going to ask this patient if they vape,’ when I see the distribution of ground glass appearance,” Dr. Ali said.

Dr. Ali said other factors, like the age of the patient – about three-quarters of EVALI patients are under age 34, according to the CDC – would spur him to ask about vaping. But because so many patients were young, discerning vape usage wasn’t always easy.  

“When you’re talking to teenagers, if you ask them upon admission, with the parents in the room, they’re going say ‘no,’ ” said Rachel Boykan, MD, a pediatric hospitalist at Stony Brook (N.Y.) Children’s. She added that her hospital is still seeing cases.

Dr. Rao said it often takes two to three people asking a patient about any vape usage before they confess.

Ms. Bernal, who was 27 at the time of her hospital admission for EVALI, said she bought vapes with THC at a retail shop in California. She’d been a traditional marijuana smoker, using the leaf product, but switched when someone told her it was healthier to vape THC than inhale smoke from burned marijuana leaves into her lungs. “I thought this was safe.”

Dr. Rao and her colleagues recently published a study of 41 teenage patients with EVALI who were seen at Children’s Medical Center Dallas between December 2018 and July 2021. All but one reported using e-cigarettes containing THC, and the CDC in its most recent report from February 2020 said about 80% of patients had used vapes containing THC.

The CDC also found that vitamin E acetate, an oily substance that allows THC to travel from the lungs to the brain quickly and an ingredient used in the food and cosmetics industries, was found in many of the lungs of EVALI patients, though not all.
 

The aftermath

The outcomes of the thousands of patients who had EVALI – and those who may still be developing it – are largely untracked.

Bonnie Halpern-Felsher, PhD, director at the Stanford (Calif.) Reach Lab that bears her name and a researcher on tobacco in youth, said she and many of her colleagues are frustrated that the CDC is not continuing to collect data on EVALI.

“I know a lot of colleagues who’ve said that they’re still seeing EVALI, but because of COVID-19 they stopped collecting the data. And that’s been very frustrating because it’s hard to say whether the kinds of lung issues you’re having are related to e-cigarettes, generally, or EVALI,” Dr. Halpern-Felsher said.

Researchers and doctors affiliated with the American Thoracic Society published a report with solutions on how to better track EVALI. They recommended that a national case registry and biorepository be created.

Doctors also worry that many cases were missed. Dr. Boykan said that while protocol dictated nurses and other clinicians ask about a history of vaping – a key part of EVALI diagnosis – many did not. Dr. Ali, the Louisville critical care physician, said EVALI symptoms of nausea, cough, and fever are associated with viral infections.

“I’m sure that some of these cases might be discharged from the emergency room as a virus,” Dr. Ali said. “Most of the time patients would get prescribed steroids for viral infections, which may help EVALI patients even though it’s never been studied.”

Dr. Rao also said the treatment regimen at Children’s MC Dallas, which included high doses of intravenous steroids, seemed to help. But the best management approach for treatment, or long-term follow up care, has not been studied.

The report in the Annals of the American Thoracic Society said prospective studies are showing that a significant portion of patients with EVALI experience prolonged respiratory issues and cognitive and mood impairment. Dr. Rao said a common thread for many of her EVALI patients has been significant stress in their lives with school or family, which led them to vape in an attempt to reduce stress.

That was certainly the case for Ms. Bernal before her hospital admission. She had recently moved across the country for her husband’s job, was trying to buy a house, and had spent months in a hotel with three children. She vaped to cope.

But she said her mental and cognitive health has worsened. Back in Louisville, she saw a neurologist, who told her that her brain had shrunk, she said. She hasn’t found a new neurologist in Portland, Ore., where her family moved a year after the EVALI episode.

But she often finds herself overwhelmed and overstimulated with tasks that she said she never had problems with before. She tears up while talking about the newfound limitations. She struggled to find a primary care physician who could medically manage her mental health and a counselor who can understand what she’s been through with EVALI.

But, “a lot of doctors aren’t educated in it, and they don’t know how to respond or they don’t know what to do,” Ms. Bernal said. “And that makes me feel like, I guess, what I had wasn’t important.”

Ms. Bernal does have a new pulmonologist and is going in for a round of pulmonary tests soon because she often finds herself unable to breathe while completing simple tasks. She is tired of rushing to the ER. She wants answers, or some kind of treatment to help her feel normal again.

“I feel like this is my fault,” Ms. Bernal said. “Had I not smoked, I would be fine, and that’s hard to live with. Every day. Telling yourself, ‘It’s your fault.’ It’s been how many years now? And I still haven’t found peace yet. I don’t know if ever will.”

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

Rashelle Bernal vaped and ended up in an induced coma for a week. She was one of almost 3,000 people who were hospitalized during 2019 and early 2020 with severe lung damage from vaping and became part of what is now known as the epidemic of e-cigarette, or vaping, product use–associated lung injury (EVALI).

For many, the EVALI epidemic is a distant, pre-COVID memory.

But the vaping-related injuries are still happening. And for Ms. Bernal, the aftermath is her reality. Her pulmonologist from that time described the harm from the vape ingredients as an oil spill in her lungs. Eventually, the toxins would probably clear. But she will likely wrestle with the injuries for a very long time.

More than 3 years later, she frequently finds herself in the emergency department.

“If I get sick, if there’s anything that irritates my lungs – it could be something as simple as pollen in the air – it will cause me to get like a bacterial infection or other issues, and I can’t breathe,” Ms. Ms. Bernal, now 30, said in a recent interview. “I get really winded, to the point where I’ll walk up the stairs and I feel like I just ran a mile.”

In 2019 and 2020, a media firestorm erupted as hospitals notified the public of outbreaks of vaping-related lung injuries. News headlines reported e-cigarettes were killing teens from Texas to the Bronx. Investigators at the U.S. Centers for Disease Control and Prevention tracked most of the cases to vitamin E acetate, an additive in illicit cannabis vaping products intended to promote the metabolism of tetrahydrocannabinol (THC). The agency stopped tracking EVALI in February 2020.

But 2 months later, in April 2020, the agency’s National Center for Health Statistics implemented a diagnostic code, U07.0, for health care professionals in the United States to diagnose EVALI for the first time. The code is also used for lung damage related to use of electronic cigarettes and “dabbing” – a method of inhaling cannabis. Damage could include inflammation of the lungs, pulmonary hemorrhage, and eosinophilic pneumonia.

The incidence of these diagnoses appears to have risen sharply since 2020. In the last three months of 2020, a total of 11,300 medical claims included the U07.0 code. That figure rose to 22,000 in 2021 and hit 31,600 in 2022, according to data compiled for and provided to Medscape by Komodo Health, a health care technology company that holds a database of more than 330 million U.S. patients from Medicare, Medicaid, and commercial insurers’ medical, pharmacy, and laboratory claims.

Harm from vaping, including EVALI, has continued.

“We’re still seeing a number of patients diagnosed with vaping disorders, but it’s not top of mind,” said Usha Periyanayagam, MD, MPH, head of clinic product and real-world evidence for Komodo and a former emergency medicine physician.
 

Where it started

Devika Rao, MD, a pediatric pulmonology specialist at UT Southwestern Medical Center, Dallas, has cared for most of her EVALI patients in the hospital, with the most recent case in early 2023. But in January, for the first time, she saw an EVALI patient in an outpatient clinic. The person had not been admitted to the hospital – like most were pre-pandemic. And like most who were seen during the pandemic, this patient had milder symptoms, not requiring intubation or take-home oxygen.

In 2019 and the beginning of 2020, many EVALI patients who were eventually hospitalized first sought help at urgent care centers or with primary care doctors and were presumed to have pneumonia or gastroenteritis and sent home.

“But they got worse, and they would present to our emergency room; their chest X-rays and CT scans showed extensive lung disease,” Dr. Rao said, adding that the damage was striking among patients all under age 18. “They were short of breath. Their oxygen levels were low. They had diminished lung function. And they had a lot of GI issues like abdominal pain and weight loss from nausea and vomiting.”

“These overwhelming inflammatory reactions that we see with EVALI,” said Karen M. Wilson, MD, MPH, a pediatric hospitalist at the University of Rochester (N.Y.) Medical Center and a tobacco use researcher. “You might find some microvascular changes with normal inhaling of smoke or aerosol, but you’re not going to find macro changes like we see with the EVALI.”

In late 2019, images of the CT scans of patients with EVALI were published, grabbing the attention of Arun Kannappan, MD, an assistant professor of pulmonary sciences and critical care at the University of Colorado Anschutz School of Medicine, Aurora. Dr. Kannappan knew a patient with such severe lung damage could develop acute respiratory distress syndrome, which means a patient would be put on a ventilator because their inflamed lungs could not oxygenate blood.

“That confers within somewhere between 30% to 50% chance of dying; it made all of the pulmonary specialists really turn their heads to make sure that we keep a lookout for it,” said Dr. Kannappan.

CT scans of lungs proved to be a critical diagnostic tool for doctors. Most of the images from patients showed acute inflammation and diffuse lung damage. Ehab Ali, MD, a critical care and pulmonary disease medicine specialist in Louisville, Ky., said the damage was often spread across both lungs in many areas and appeared opaque and hazy, known as “ground glass.” COVID-19, meanwhile, appeared differently in lung scans, often with damage that was more isolated.

But many diseases carry a “ground glass” appearance, with many potential causes, like infections, cigarette smoke, or an autoimmune condition.

“Before you even talk to the patient, you can immediately put it in your mind that ‘I’m going to ask this patient if they vape,’ when I see the distribution of ground glass appearance,” Dr. Ali said.

Dr. Ali said other factors, like the age of the patient – about three-quarters of EVALI patients are under age 34, according to the CDC – would spur him to ask about vaping. But because so many patients were young, discerning vape usage wasn’t always easy.  

“When you’re talking to teenagers, if you ask them upon admission, with the parents in the room, they’re going say ‘no,’ ” said Rachel Boykan, MD, a pediatric hospitalist at Stony Brook (N.Y.) Children’s. She added that her hospital is still seeing cases.

Dr. Rao said it often takes two to three people asking a patient about any vape usage before they confess.

Ms. Bernal, who was 27 at the time of her hospital admission for EVALI, said she bought vapes with THC at a retail shop in California. She’d been a traditional marijuana smoker, using the leaf product, but switched when someone told her it was healthier to vape THC than inhale smoke from burned marijuana leaves into her lungs. “I thought this was safe.”

Dr. Rao and her colleagues recently published a study of 41 teenage patients with EVALI who were seen at Children’s Medical Center Dallas between December 2018 and July 2021. All but one reported using e-cigarettes containing THC, and the CDC in its most recent report from February 2020 said about 80% of patients had used vapes containing THC.

The CDC also found that vitamin E acetate, an oily substance that allows THC to travel from the lungs to the brain quickly and an ingredient used in the food and cosmetics industries, was found in many of the lungs of EVALI patients, though not all.
 

The aftermath

The outcomes of the thousands of patients who had EVALI – and those who may still be developing it – are largely untracked.

Bonnie Halpern-Felsher, PhD, director at the Stanford (Calif.) Reach Lab that bears her name and a researcher on tobacco in youth, said she and many of her colleagues are frustrated that the CDC is not continuing to collect data on EVALI.

“I know a lot of colleagues who’ve said that they’re still seeing EVALI, but because of COVID-19 they stopped collecting the data. And that’s been very frustrating because it’s hard to say whether the kinds of lung issues you’re having are related to e-cigarettes, generally, or EVALI,” Dr. Halpern-Felsher said.

Researchers and doctors affiliated with the American Thoracic Society published a report with solutions on how to better track EVALI. They recommended that a national case registry and biorepository be created.

Doctors also worry that many cases were missed. Dr. Boykan said that while protocol dictated nurses and other clinicians ask about a history of vaping – a key part of EVALI diagnosis – many did not. Dr. Ali, the Louisville critical care physician, said EVALI symptoms of nausea, cough, and fever are associated with viral infections.

“I’m sure that some of these cases might be discharged from the emergency room as a virus,” Dr. Ali said. “Most of the time patients would get prescribed steroids for viral infections, which may help EVALI patients even though it’s never been studied.”

Dr. Rao also said the treatment regimen at Children’s MC Dallas, which included high doses of intravenous steroids, seemed to help. But the best management approach for treatment, or long-term follow up care, has not been studied.

The report in the Annals of the American Thoracic Society said prospective studies are showing that a significant portion of patients with EVALI experience prolonged respiratory issues and cognitive and mood impairment. Dr. Rao said a common thread for many of her EVALI patients has been significant stress in their lives with school or family, which led them to vape in an attempt to reduce stress.

That was certainly the case for Ms. Bernal before her hospital admission. She had recently moved across the country for her husband’s job, was trying to buy a house, and had spent months in a hotel with three children. She vaped to cope.

But she said her mental and cognitive health has worsened. Back in Louisville, she saw a neurologist, who told her that her brain had shrunk, she said. She hasn’t found a new neurologist in Portland, Ore., where her family moved a year after the EVALI episode.

But she often finds herself overwhelmed and overstimulated with tasks that she said she never had problems with before. She tears up while talking about the newfound limitations. She struggled to find a primary care physician who could medically manage her mental health and a counselor who can understand what she’s been through with EVALI.

But, “a lot of doctors aren’t educated in it, and they don’t know how to respond or they don’t know what to do,” Ms. Bernal said. “And that makes me feel like, I guess, what I had wasn’t important.”

Ms. Bernal does have a new pulmonologist and is going in for a round of pulmonary tests soon because she often finds herself unable to breathe while completing simple tasks. She is tired of rushing to the ER. She wants answers, or some kind of treatment to help her feel normal again.

“I feel like this is my fault,” Ms. Bernal said. “Had I not smoked, I would be fine, and that’s hard to live with. Every day. Telling yourself, ‘It’s your fault.’ It’s been how many years now? And I still haven’t found peace yet. I don’t know if ever will.”

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

Cardiovascular disease deaths were significantly more common on days of high pollution and for the following 2 days, compared with other days, based on data from nearly 88,000 deaths over a 5-year period.

Previous research has shown the harmful effect of air pollution on human health in highly polluted areas, but Eastern Poland, a region with so-called “Polish smog” has exceptionally high levels of pollution. However, the specific impact of Polish smog, caused primarily by burning coal, on cardiovascular disease (CVD) mortality has not been well studied, said Michal Swieczkowski, MD, of the Medical University of Bialystok (Poland) in a presentation at the annual congress of the European Association of Preventive Cardiology.

Ja'Crispy/iStock/Getty Images Plus

Dr. Swieczkowski and colleagues reviewed all-cause deaths from five main cities in Eastern Poland during 2016-2020 for associations with pollution levels and days when deaths occurred. Mortality data were obtained from the Central Statistical Office. Air pollution concentrations for two types of particulate matter (PM2.5, PM10) and nitrogen oxide were collected from the Voivodeship Inspectorate for Environmental Protection. The main sources of the pollutants were road traffic and household heaters using coal or wood.

The final analysis included nearly 6 million person-years of follow-up. The researchers used a time-stratified case-crossover design. For each participant, the researchers compared levels of each pollutant on the day of the week a death occurred (such as a Wednesday) with pollutant levels on the same day of the week without any deaths in the same month (the remaining Wednesdays of that month). This design eliminated the potential confounding effects of participant characteristics, including other cardiovascular risk factors such as smoking and hyperlipidemia, and time trends. Essentially, participants “served as their own controls,” Dr. Swieczkowski said. The researchers conducted similar analyses for pollution levels 1 day and 2 days before a death occurred.

Overall, 87,990 deaths were identified during the study period; of these, 34,907 were from CVD, 9,688 from acute coronary syndromes, and 3,776 from ischemic stroke.

“Exposure to PM2.5 and PM10 was associated with increased mortality on the day of exposure, the next day, and up to 2 days after exposure,” said Dr. Swieczkowski.

Overall, an increase of 10 mcg/m³ in the three pollutants was significantly associated with increase in CVD mortality on the day of exposure to the increased pollution levels, with odds ratios of 1.034, 1.033, and 1.083 for PM2.5, PM10, and NO₂, respectively (all P < .001).

The risks of dying from CVD were similar 1 and 2 days after the polluted day.

An increase in PM levels, but not NO₂, was significantly associated with acute coronary syndrome (ACS) on the day of exposure to increased pollutants (ORs, 1.029 for PM2.5 [P = .002] and 1.015 [P = .049] for PM10). Both ischemic stroke and ACS mortality were significantly higher at 1 day after exposure, compared with other days. Ischemic stroke was associated with increases in PM2.5 and PM10, while ACS was associated with increases in PM2.5, PM10, and NO₂.

When stratified by gender, the effects were more noticeable in women, Dr. Swieczkowski said. “Exposure to both types of particulate caused increased mortality due to acute coronary syndrome as well as ischemic stroke.” Among men, only death from acute coronary syndrome was significantly associated with exposure to increased particulate matter.

In a head-to-head comparison, women were more vulnerable to air pollution by up to 2.5%, he added.

When stratified by age, the effects of all three pollutants were associated with increased risk of death from ischemic stroke and ACS in participants older than 65 years. For those aged 65 years and younger, the only significant association was between ACS-associated mortality and ischemic stroke.

The results suggest “a special need for developing calculators to estimate the risk of CVD incidence depending on the place of residence that could be used for everyday practice,” said Dr. Swieczkowski. “Systemic changes should become a priority for policy makers, and, simultaneously, we as physicians should educate and protect our patients, especially those with high risk of cardiovascular disease,” he said.
 

Gender differences rooted in anatomy

When asked for an explanation of the difference in the impact of pollution on mortality between men and women, Dr. Swieczkowski explained that women are likely more vulnerable because of differences in anatomy of the pharynx and larynx, and breathing patterns. Previous studies have shown that air pollution causes more oxidative stress in women. Also, in the current study, the mean age of the women was 8 to 9 years older, he said.

The study design was an “elegant way to take away the impact of other cardiovascular risk factors,” noted session moderator Maryam Kavousi, MD, of Erasmus University Medical Center, Rotterdam, the Netherlands.

The study was supported by the National Science Centre, Poland. The researchers had no financial conflicts to disclose.
 

Cardiovascular disease deaths were significantly more common on days of high pollution and for the following 2 days, compared with other days, based on data from nearly 88,000 deaths over a 5-year period.

Previous research has shown the harmful effect of air pollution on human health in highly polluted areas, but Eastern Poland, a region with so-called “Polish smog” has exceptionally high levels of pollution. However, the specific impact of Polish smog, caused primarily by burning coal, on cardiovascular disease (CVD) mortality has not been well studied, said Michal Swieczkowski, MD, of the Medical University of Bialystok (Poland) in a presentation at the annual congress of the European Association of Preventive Cardiology.

Ja&#039;Crispy/iStock/Getty Images Plus

Dr. Swieczkowski and colleagues reviewed all-cause deaths from five main cities in Eastern Poland during 2016-2020 for associations with pollution levels and days when deaths occurred. Mortality data were obtained from the Central Statistical Office. Air pollution concentrations for two types of particulate matter (PM2.5, PM10) and nitrogen oxide were collected from the Voivodeship Inspectorate for Environmental Protection. The main sources of the pollutants were road traffic and household heaters using coal or wood.

The final analysis included nearly 6 million person-years of follow-up. The researchers used a time-stratified case-crossover design. For each participant, the researchers compared levels of each pollutant on the day of the week a death occurred (such as a Wednesday) with pollutant levels on the same day of the week without any deaths in the same month (the remaining Wednesdays of that month). This design eliminated the potential confounding effects of participant characteristics, including other cardiovascular risk factors such as smoking and hyperlipidemia, and time trends. Essentially, participants “served as their own controls,” Dr. Swieczkowski said. The researchers conducted similar analyses for pollution levels 1 day and 2 days before a death occurred.

Overall, 87,990 deaths were identified during the study period; of these, 34,907 were from CVD, 9,688 from acute coronary syndromes, and 3,776 from ischemic stroke.

“Exposure to PM2.5 and PM10 was associated with increased mortality on the day of exposure, the next day, and up to 2 days after exposure,” said Dr. Swieczkowski.

Overall, an increase of 10 mcg/m³ in the three pollutants was significantly associated with increase in CVD mortality on the day of exposure to the increased pollution levels, with odds ratios of 1.034, 1.033, and 1.083 for PM2.5, PM10, and NO₂, respectively (all P < .001).

The risks of dying from CVD were similar 1 and 2 days after the polluted day.

An increase in PM levels, but not NO₂, was significantly associated with acute coronary syndrome (ACS) on the day of exposure to increased pollutants (ORs, 1.029 for PM2.5 [P = .002] and 1.015 [P = .049] for PM10). Both ischemic stroke and ACS mortality were significantly higher at 1 day after exposure, compared with other days. Ischemic stroke was associated with increases in PM2.5 and PM10, while ACS was associated with increases in PM2.5, PM10, and NO₂.

When stratified by gender, the effects were more noticeable in women, Dr. Swieczkowski said. “Exposure to both types of particulate caused increased mortality due to acute coronary syndrome as well as ischemic stroke.” Among men, only death from acute coronary syndrome was significantly associated with exposure to increased particulate matter.

In a head-to-head comparison, women were more vulnerable to air pollution by up to 2.5%, he added.

When stratified by age, the effects of all three pollutants were associated with increased risk of death from ischemic stroke and ACS in participants older than 65 years. For those aged 65 years and younger, the only significant association was between ACS-associated mortality and ischemic stroke.

The results suggest “a special need for developing calculators to estimate the risk of CVD incidence depending on the place of residence that could be used for everyday practice,” said Dr. Swieczkowski. “Systemic changes should become a priority for policy makers, and, simultaneously, we as physicians should educate and protect our patients, especially those with high risk of cardiovascular disease,” he said.
 

Gender differences rooted in anatomy

When asked for an explanation of the difference in the impact of pollution on mortality between men and women, Dr. Swieczkowski explained that women are likely more vulnerable because of differences in anatomy of the pharynx and larynx, and breathing patterns. Previous studies have shown that air pollution causes more oxidative stress in women. Also, in the current study, the mean age of the women was 8 to 9 years older, he said.

The study design was an “elegant way to take away the impact of other cardiovascular risk factors,” noted session moderator Maryam Kavousi, MD, of Erasmus University Medical Center, Rotterdam, the Netherlands.

The study was supported by the National Science Centre, Poland. The researchers had no financial conflicts to disclose.
 

Cardiovascular disease deaths were significantly more common on days of high pollution and for the following 2 days, compared with other days, based on data from nearly 88,000 deaths over a 5-year period.

Previous research has shown the harmful effect of air pollution on human health in highly polluted areas, but Eastern Poland, a region with so-called “Polish smog” has exceptionally high levels of pollution. However, the specific impact of Polish smog, caused primarily by burning coal, on cardiovascular disease (CVD) mortality has not been well studied, said Michal Swieczkowski, MD, of the Medical University of Bialystok (Poland) in a presentation at the annual congress of the European Association of Preventive Cardiology.

Ja&#039;Crispy/iStock/Getty Images Plus

Dr. Swieczkowski and colleagues reviewed all-cause deaths from five main cities in Eastern Poland during 2016-2020 for associations with pollution levels and days when deaths occurred. Mortality data were obtained from the Central Statistical Office. Air pollution concentrations for two types of particulate matter (PM2.5, PM10) and nitrogen oxide were collected from the Voivodeship Inspectorate for Environmental Protection. The main sources of the pollutants were road traffic and household heaters using coal or wood.

The final analysis included nearly 6 million person-years of follow-up. The researchers used a time-stratified case-crossover design. For each participant, the researchers compared levels of each pollutant on the day of the week a death occurred (such as a Wednesday) with pollutant levels on the same day of the week without any deaths in the same month (the remaining Wednesdays of that month). This design eliminated the potential confounding effects of participant characteristics, including other cardiovascular risk factors such as smoking and hyperlipidemia, and time trends. Essentially, participants “served as their own controls,” Dr. Swieczkowski said. The researchers conducted similar analyses for pollution levels 1 day and 2 days before a death occurred.

Overall, 87,990 deaths were identified during the study period; of these, 34,907 were from CVD, 9,688 from acute coronary syndromes, and 3,776 from ischemic stroke.

“Exposure to PM2.5 and PM10 was associated with increased mortality on the day of exposure, the next day, and up to 2 days after exposure,” said Dr. Swieczkowski.

Overall, an increase of 10 mcg/m³ in the three pollutants was significantly associated with increase in CVD mortality on the day of exposure to the increased pollution levels, with odds ratios of 1.034, 1.033, and 1.083 for PM2.5, PM10, and NO₂, respectively (all P < .001).

The risks of dying from CVD were similar 1 and 2 days after the polluted day.

An increase in PM levels, but not NO₂, was significantly associated with acute coronary syndrome (ACS) on the day of exposure to increased pollutants (ORs, 1.029 for PM2.5 [P = .002] and 1.015 [P = .049] for PM10). Both ischemic stroke and ACS mortality were significantly higher at 1 day after exposure, compared with other days. Ischemic stroke was associated with increases in PM2.5 and PM10, while ACS was associated with increases in PM2.5, PM10, and NO₂.

When stratified by gender, the effects were more noticeable in women, Dr. Swieczkowski said. “Exposure to both types of particulate caused increased mortality due to acute coronary syndrome as well as ischemic stroke.” Among men, only death from acute coronary syndrome was significantly associated with exposure to increased particulate matter.

In a head-to-head comparison, women were more vulnerable to air pollution by up to 2.5%, he added.

When stratified by age, the effects of all three pollutants were associated with increased risk of death from ischemic stroke and ACS in participants older than 65 years. For those aged 65 years and younger, the only significant association was between ACS-associated mortality and ischemic stroke.

The results suggest “a special need for developing calculators to estimate the risk of CVD incidence depending on the place of residence that could be used for everyday practice,” said Dr. Swieczkowski. “Systemic changes should become a priority for policy makers, and, simultaneously, we as physicians should educate and protect our patients, especially those with high risk of cardiovascular disease,” he said.
 

Gender differences rooted in anatomy

When asked for an explanation of the difference in the impact of pollution on mortality between men and women, Dr. Swieczkowski explained that women are likely more vulnerable because of differences in anatomy of the pharynx and larynx, and breathing patterns. Previous studies have shown that air pollution causes more oxidative stress in women. Also, in the current study, the mean age of the women was 8 to 9 years older, he said.

The study design was an “elegant way to take away the impact of other cardiovascular risk factors,” noted session moderator Maryam Kavousi, MD, of Erasmus University Medical Center, Rotterdam, the Netherlands.

The study was supported by the National Science Centre, Poland. The researchers had no financial conflicts to disclose.
 

This article is part of a series from Medscape on vaping.

Every day, Sonia Sharma, PA, meets people like Natalie H., who is trying to quit vaping.

Natalie, a member of the nicotine addiction support group at the University of California San Francisco’s Fontana Tobacco Treatment Center, switched from traditional cigarettes to vaping but found the electronic version just as addictive and eventually decided to quit using nicotine completely.

“I went from being an occasional cigarette smoker, a few a month, to a daily vaper,” said Natalie, who preferred not to give her last name to protect her privacy. “Vaping made my nicotine addiction worse, not better.”

“We have people tell us they vape before their feet hit the ground in the morning,” said Ms. Sharma, who coleads Natalie’s support group at UCSF. Ms. Sharma has met individuals who had smoked four to five cigarettes a day, switched to e-cigarettes to quit smoking, then vaped the equivalent of a pack a day. Others had switched to vapes to quit but ended up both vaping and smoking again. And others picked up vaping without ever smoking. They want to quit, she said, but are not sure how.

Researchers from the National Institutes of Health in 2020 reported that 5.6 million  adults in the United States vaped. A little over 57% of people said they started using e-cigarettes to quit smoking traditional cigarettes. Another study in 2021 based on survey data found that about 60% of e-cigarette users wanted to quit their vaping habit. 

Vaping has been marketed as a way to help people kick their smoking habit. Research is inconclusive on this claim. But unlike cessation tools like nicotine gums or lozenges, using vapes for cessation is uncharted territory. Vapers lack guidance for how to use the devices to quit, and they have even less direction on what to do if they develop an addiction to the vapes themselves.
 

A new addiction?

Monica Hanna, MPH, assistant director of the Nicotine and Tobacco Recovery Program at RWJBarnabas Health’s Institute for Prevention and Recovery in New Jersey, said she has witnessed a higher level of nicotine addiction in the vapers with whom she has worked.

“When someone takes a hit from a vaping device, it doesn’t generate the burn it would from traditional tobacco,” Ms. Hanna said. “This causes people to take a deeper pull, and when they take a deeper pull, they establish a higher level of nicotine dependence over time.” 

A 2019 study of nearly 900 people published in the New England Journal of Medicine found that smokers who used vapes for cessation were twice as likely to have quit smoking cigarettes as those who used other nicotine replacement therapy. However, 80% of people who switched to vaping were using e-cigarettes a year after they tried to quit smoking.

Given that potential for addiction, Nancy Rigotti, MD, director of Massachusetts General Hospital’s Tobacco Research and Treatment Center in Boston, said patients must use vapes “properly” for cessation. That means giving up smoking completely and quitting vapes as soon as patients are sure they will not go back to smoking tobacco.

“We are going to need to help these people to stop vaping,” said Dr. Rigotti, who is working with Achieve Life Sciences, a pharmaceutical company developing a prescription drug to treat nicotine addiction from vapes and cigarettes.

And many nicotine users who have tried vaping to quit smoking end up becoming dual users.

“It’s important to stress that health benefits [of switching to vaping] only occur if the switch to vapes is complete and permanent. So far, that appears difficult to do for most people who smoke, and in my anecdotal experience it has not worked,” said J. Taylor Hays, MD, the former medical director of Mayo Clinic’s Nicotine Dependence Center in Rochester, Minn.

Besides challenges in communicating the current evidence, no established method exists to help vapers quit, according to Nigar Nargis, PhD, senior scientific director of tobacco control research at the American Cancer Society. 

“There are some experimental methods like using social interventions, counseling, and some educational campaigns,” Dr. Nargis said. “[Little] progress has been done in terms of clinical interventions.”

Unlike cessation products such as gum or a nicotine patch, which have clear recommendations for duration of use, similar guidelines don’t exist for vapes, in part because the U.S. Food and Drug Administration hasn’t yet granted approval of vapes as cessation products.

Alex Clark, the CEO of Consumer Advocates for Smoke-free Alternatives Association, a nonprofit group that supports vaping, said people could vape for longer and still benefit from making the switch from traditional cigarettes.

“The most important thing is that people start replacing cigarettes with a smoke-free product and continue until they’ve completely switched,” said Mr. Clark, whose group accepts donations from the e-cigarette industry. “Following switching, people are encouraged to continue with the product for as long as they feel necessary.”

But 2013 guidelines from the FDA advised makers of nicotine-replacement therapies – including gums, patches, and lozenges – to include labeling that advises users to complete treatment. According to the agency, if a person feels like they “need to use [the NRT product] for a longer period to keep from smoking, talk to your health care provider.”

Dr. Hays, who is now an emeritus professor at the Mayo Clinic, said he would not recommend patients try vaping as a cessation device given the availability of more proven techniques such as patches and gums. If a patient insists, vaping could be considered under the medical guidance of a cessation professional. He also advised people purchase products only from large tobacco companies that are likely to have “reasonable quality control.” Hundreds of vaping devices are on the market, and they are not all equivalent, he said.

But when an e-cigarette user wants to quit vaping, guidance might boil down to using traditional tobacco cessation methods like gums and lozenges because few tools exist to help people with a vaping-specific addiction.

The long-term health outcomes of vaping are also unclear, and decades will pass before scientists are able to make conclusions, according to Thomas Eissenberg, PhD, codirector of Virginia Commonwealth University’s Center for the Study of Tobacco Products in Richmond.

“I don’t think anyone knows what the long-term effects of heated propylene glycol and vegetable glycerin and flavors intended as food ingredients are, especially when these compounds are inhaled hundreds of times a day, week after week, year after year,” Dr. Eissenberg said.

Dr. Rigotti reported that she receives no funding from the tobacco or e-cigarette industry. She is working with Achieve Life Sciences to develop a tool for vaping cessation. Dr. Eissenberg, Ms. Hanna, Dr. Hays, Dr. Nargis, and Ms. Sharma reported no funding from the tobacco or e-cigarette industry.

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

This article is part of a series from Medscape on vaping.

Every day, Sonia Sharma, PA, meets people like Natalie H., who is trying to quit vaping.

Natalie, a member of the nicotine addiction support group at the University of California San Francisco’s Fontana Tobacco Treatment Center, switched from traditional cigarettes to vaping but found the electronic version just as addictive and eventually decided to quit using nicotine completely.

“I went from being an occasional cigarette smoker, a few a month, to a daily vaper,” said Natalie, who preferred not to give her last name to protect her privacy. “Vaping made my nicotine addiction worse, not better.”

“We have people tell us they vape before their feet hit the ground in the morning,” said Ms. Sharma, who coleads Natalie’s support group at UCSF. Ms. Sharma has met individuals who had smoked four to five cigarettes a day, switched to e-cigarettes to quit smoking, then vaped the equivalent of a pack a day. Others had switched to vapes to quit but ended up both vaping and smoking again. And others picked up vaping without ever smoking. They want to quit, she said, but are not sure how.

Researchers from the National Institutes of Health in 2020 reported that 5.6 million  adults in the United States vaped. A little over 57% of people said they started using e-cigarettes to quit smoking traditional cigarettes. Another study in 2021 based on survey data found that about 60% of e-cigarette users wanted to quit their vaping habit. 

Vaping has been marketed as a way to help people kick their smoking habit. Research is inconclusive on this claim. But unlike cessation tools like nicotine gums or lozenges, using vapes for cessation is uncharted territory. Vapers lack guidance for how to use the devices to quit, and they have even less direction on what to do if they develop an addiction to the vapes themselves.
 

A new addiction?

Monica Hanna, MPH, assistant director of the Nicotine and Tobacco Recovery Program at RWJBarnabas Health’s Institute for Prevention and Recovery in New Jersey, said she has witnessed a higher level of nicotine addiction in the vapers with whom she has worked.

“When someone takes a hit from a vaping device, it doesn’t generate the burn it would from traditional tobacco,” Ms. Hanna said. “This causes people to take a deeper pull, and when they take a deeper pull, they establish a higher level of nicotine dependence over time.” 

A 2019 study of nearly 900 people published in the New England Journal of Medicine found that smokers who used vapes for cessation were twice as likely to have quit smoking cigarettes as those who used other nicotine replacement therapy. However, 80% of people who switched to vaping were using e-cigarettes a year after they tried to quit smoking.

Given that potential for addiction, Nancy Rigotti, MD, director of Massachusetts General Hospital’s Tobacco Research and Treatment Center in Boston, said patients must use vapes “properly” for cessation. That means giving up smoking completely and quitting vapes as soon as patients are sure they will not go back to smoking tobacco.

“We are going to need to help these people to stop vaping,” said Dr. Rigotti, who is working with Achieve Life Sciences, a pharmaceutical company developing a prescription drug to treat nicotine addiction from vapes and cigarettes.

And many nicotine users who have tried vaping to quit smoking end up becoming dual users.

“It’s important to stress that health benefits [of switching to vaping] only occur if the switch to vapes is complete and permanent. So far, that appears difficult to do for most people who smoke, and in my anecdotal experience it has not worked,” said J. Taylor Hays, MD, the former medical director of Mayo Clinic’s Nicotine Dependence Center in Rochester, Minn.

Besides challenges in communicating the current evidence, no established method exists to help vapers quit, according to Nigar Nargis, PhD, senior scientific director of tobacco control research at the American Cancer Society. 

“There are some experimental methods like using social interventions, counseling, and some educational campaigns,” Dr. Nargis said. “[Little] progress has been done in terms of clinical interventions.”

Unlike cessation products such as gum or a nicotine patch, which have clear recommendations for duration of use, similar guidelines don’t exist for vapes, in part because the U.S. Food and Drug Administration hasn’t yet granted approval of vapes as cessation products.

Alex Clark, the CEO of Consumer Advocates for Smoke-free Alternatives Association, a nonprofit group that supports vaping, said people could vape for longer and still benefit from making the switch from traditional cigarettes.

“The most important thing is that people start replacing cigarettes with a smoke-free product and continue until they’ve completely switched,” said Mr. Clark, whose group accepts donations from the e-cigarette industry. “Following switching, people are encouraged to continue with the product for as long as they feel necessary.”

But 2013 guidelines from the FDA advised makers of nicotine-replacement therapies – including gums, patches, and lozenges – to include labeling that advises users to complete treatment. According to the agency, if a person feels like they “need to use [the NRT product] for a longer period to keep from smoking, talk to your health care provider.”

Dr. Hays, who is now an emeritus professor at the Mayo Clinic, said he would not recommend patients try vaping as a cessation device given the availability of more proven techniques such as patches and gums. If a patient insists, vaping could be considered under the medical guidance of a cessation professional. He also advised people purchase products only from large tobacco companies that are likely to have “reasonable quality control.” Hundreds of vaping devices are on the market, and they are not all equivalent, he said.

But when an e-cigarette user wants to quit vaping, guidance might boil down to using traditional tobacco cessation methods like gums and lozenges because few tools exist to help people with a vaping-specific addiction.

The long-term health outcomes of vaping are also unclear, and decades will pass before scientists are able to make conclusions, according to Thomas Eissenberg, PhD, codirector of Virginia Commonwealth University’s Center for the Study of Tobacco Products in Richmond.

“I don’t think anyone knows what the long-term effects of heated propylene glycol and vegetable glycerin and flavors intended as food ingredients are, especially when these compounds are inhaled hundreds of times a day, week after week, year after year,” Dr. Eissenberg said.

Dr. Rigotti reported that she receives no funding from the tobacco or e-cigarette industry. She is working with Achieve Life Sciences to develop a tool for vaping cessation. Dr. Eissenberg, Ms. Hanna, Dr. Hays, Dr. Nargis, and Ms. Sharma reported no funding from the tobacco or e-cigarette industry.

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

This article is part of a series from Medscape on vaping.

Every day, Sonia Sharma, PA, meets people like Natalie H., who is trying to quit vaping.

Natalie, a member of the nicotine addiction support group at the University of California San Francisco’s Fontana Tobacco Treatment Center, switched from traditional cigarettes to vaping but found the electronic version just as addictive and eventually decided to quit using nicotine completely.

“I went from being an occasional cigarette smoker, a few a month, to a daily vaper,” said Natalie, who preferred not to give her last name to protect her privacy. “Vaping made my nicotine addiction worse, not better.”

“We have people tell us they vape before their feet hit the ground in the morning,” said Ms. Sharma, who coleads Natalie’s support group at UCSF. Ms. Sharma has met individuals who had smoked four to five cigarettes a day, switched to e-cigarettes to quit smoking, then vaped the equivalent of a pack a day. Others had switched to vapes to quit but ended up both vaping and smoking again. And others picked up vaping without ever smoking. They want to quit, she said, but are not sure how.

Researchers from the National Institutes of Health in 2020 reported that 5.6 million  adults in the United States vaped. A little over 57% of people said they started using e-cigarettes to quit smoking traditional cigarettes. Another study in 2021 based on survey data found that about 60% of e-cigarette users wanted to quit their vaping habit. 

Vaping has been marketed as a way to help people kick their smoking habit. Research is inconclusive on this claim. But unlike cessation tools like nicotine gums or lozenges, using vapes for cessation is uncharted territory. Vapers lack guidance for how to use the devices to quit, and they have even less direction on what to do if they develop an addiction to the vapes themselves.
 

A new addiction?

Monica Hanna, MPH, assistant director of the Nicotine and Tobacco Recovery Program at RWJBarnabas Health’s Institute for Prevention and Recovery in New Jersey, said she has witnessed a higher level of nicotine addiction in the vapers with whom she has worked.

“When someone takes a hit from a vaping device, it doesn’t generate the burn it would from traditional tobacco,” Ms. Hanna said. “This causes people to take a deeper pull, and when they take a deeper pull, they establish a higher level of nicotine dependence over time.” 

A 2019 study of nearly 900 people published in the New England Journal of Medicine found that smokers who used vapes for cessation were twice as likely to have quit smoking cigarettes as those who used other nicotine replacement therapy. However, 80% of people who switched to vaping were using e-cigarettes a year after they tried to quit smoking.

Given that potential for addiction, Nancy Rigotti, MD, director of Massachusetts General Hospital’s Tobacco Research and Treatment Center in Boston, said patients must use vapes “properly” for cessation. That means giving up smoking completely and quitting vapes as soon as patients are sure they will not go back to smoking tobacco.

“We are going to need to help these people to stop vaping,” said Dr. Rigotti, who is working with Achieve Life Sciences, a pharmaceutical company developing a prescription drug to treat nicotine addiction from vapes and cigarettes.

And many nicotine users who have tried vaping to quit smoking end up becoming dual users.

“It’s important to stress that health benefits [of switching to vaping] only occur if the switch to vapes is complete and permanent. So far, that appears difficult to do for most people who smoke, and in my anecdotal experience it has not worked,” said J. Taylor Hays, MD, the former medical director of Mayo Clinic’s Nicotine Dependence Center in Rochester, Minn.

Besides challenges in communicating the current evidence, no established method exists to help vapers quit, according to Nigar Nargis, PhD, senior scientific director of tobacco control research at the American Cancer Society. 

“There are some experimental methods like using social interventions, counseling, and some educational campaigns,” Dr. Nargis said. “[Little] progress has been done in terms of clinical interventions.”

Unlike cessation products such as gum or a nicotine patch, which have clear recommendations for duration of use, similar guidelines don’t exist for vapes, in part because the U.S. Food and Drug Administration hasn’t yet granted approval of vapes as cessation products.

Alex Clark, the CEO of Consumer Advocates for Smoke-free Alternatives Association, a nonprofit group that supports vaping, said people could vape for longer and still benefit from making the switch from traditional cigarettes.

“The most important thing is that people start replacing cigarettes with a smoke-free product and continue until they’ve completely switched,” said Mr. Clark, whose group accepts donations from the e-cigarette industry. “Following switching, people are encouraged to continue with the product for as long as they feel necessary.”

But 2013 guidelines from the FDA advised makers of nicotine-replacement therapies – including gums, patches, and lozenges – to include labeling that advises users to complete treatment. According to the agency, if a person feels like they “need to use [the NRT product] for a longer period to keep from smoking, talk to your health care provider.”

Dr. Hays, who is now an emeritus professor at the Mayo Clinic, said he would not recommend patients try vaping as a cessation device given the availability of more proven techniques such as patches and gums. If a patient insists, vaping could be considered under the medical guidance of a cessation professional. He also advised people purchase products only from large tobacco companies that are likely to have “reasonable quality control.” Hundreds of vaping devices are on the market, and they are not all equivalent, he said.

But when an e-cigarette user wants to quit vaping, guidance might boil down to using traditional tobacco cessation methods like gums and lozenges because few tools exist to help people with a vaping-specific addiction.

The long-term health outcomes of vaping are also unclear, and decades will pass before scientists are able to make conclusions, according to Thomas Eissenberg, PhD, codirector of Virginia Commonwealth University’s Center for the Study of Tobacco Products in Richmond.

“I don’t think anyone knows what the long-term effects of heated propylene glycol and vegetable glycerin and flavors intended as food ingredients are, especially when these compounds are inhaled hundreds of times a day, week after week, year after year,” Dr. Eissenberg said.

Dr. Rigotti reported that she receives no funding from the tobacco or e-cigarette industry. She is working with Achieve Life Sciences to develop a tool for vaping cessation. Dr. Eissenberg, Ms. Hanna, Dr. Hays, Dr. Nargis, and Ms. Sharma reported no funding from the tobacco or e-cigarette industry.

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

Jake Warn calls vaping “a toxic artificial love.”

Jake, of Winslow, Maine, was 16 years old when he began vaping. Unlike cigarettes, vaping can be odorless, and its smoke leaves no trace, which allowed him and his friends to use the devices in school bathrooms without fear of being caught.

He would use an entire cartridge containing the vape liquid, the equivalent of smoking one pack of tobacco cigarettes, within 1 school day. By the fall semester of his first year in college, Jake said his use had increased even more.

“It got pricey, so that’s when I really started to notice” the extent of his dependency, he said recently.

Vaping rates among teenagers in Maine doubled from 15.3% to 28.7% between 2017 and 2019, while Jake was in high school. In 2021, 11% of high schoolers across the nation said they regularly smoked e-cigarettes, and an estimated 28% have ever tried the devices, according to the Centers for Disease Control and Prevention.

The Food and Drug Administration classifies e-cigarettes as a tobacco product because many contain nicotine, which comes from tobacco. Like Jake, the habit is likely to carry into adulthood for many who start in their teenage years, experts say.

Electronic nicotine delivery systems (ENDS) such as vapes have been touted by their manufacturers and by some in the medical field as a healthier alternative to cigarettes and as a method to help smokers give up the habit.

But, that’s not how Jake – who had never used combustible cigarettes – picked up vaping, or how he sold the idea to his mother.

“It’s all organic and natural flavoring, it’s just flavored water,” Mary Lou Warn recalled her son saying to her. She researched the health effects of vaping but didn’t find much online. “I knew they were dangerous because you don’t put anything in your lungs that isn’t fresh air.”

A determined athlete in high school, Jake found that his asthma worsened as he transitioned to college, especially when he ran a track meet or during a soccer game.

Mrs. Warn noticed changes off the field, too.

“He was coughing constantly, he wasn’t sleeping well, he wasn’t eating well,” she said. “I knew the addiction was taking over.”

Vaping irritated Jake’s throat, and he would get nosebleeds that he couldn’t stop, she added.

Since Mrs. Warn first looked into the effects of e-cigarettes on respiratory health back in 2017, many studies have been conducted of the short-term health outcomes for first-time smokers who never used combustible tobacco products. Studies suggest that vaping may worsen bronchitis and asthma, raise blood pressure, interfere with brain development in young users, suppress the immune system, and increase the risk of developing a chronic lung disease (Am J Prev Med. 2020 Feb;58[2]:182-90). Studies of mice and cell cultures have found that the vapor or extracts from vapes damage the chemical structure of DNA.

Still, the limited number of long-term human studies has made it hard to know what the health outcomes of e-cigarette users will be in the future. Conclusive studies linking commercial cigarette use to deaths from heart disease and cancer didn’t emerge until the mid-1950s, decades after manufacturers began mass production and marketing in the early 20th century.

Years could pass before researchers gain a clearer understanding of the health implications of long-term e-cigarette use, according to Nigar Nargis, PhD, senior scientific director of tobacco control research at the American Cancer Society.

“There hasn’t been any such study to establish the direct link from ENDS to cancer, but it is understood that it [vaping] may promote the development of cancer and lung damage and inflammation,” Dr. Nargis said.

For decades, advocates built awareness of the harms of tobacco use, which led to a sharp decline in tobacco-related illnesses such as lung cancer. But Hilary Schneider, Maine’s director of government relations for the ACS Cancer Action Network, said she fears the uptick in the use of vapes – especially among those who never smoked or those who use both combustible cigarettes and e-cigarettes – may reverse declines in the rates of smoking-relating diseases.

Multiple studies suggest that inhaling chemicals found in e-cigarettes – including nicotine-carrying aerosols – can damage arteries and inflame and injure the lungs.

Vapes “basically have created a pediatric tobacco-use epidemic,” Ms. Schneider said. “What we’re seeing is unprecedented tobacco use rates, higher rates than we’ve seen in decades.”

One reason many young people start vaping is the attraction to flavors, which range from classic menthol to fruits and sweets. A handful of states have enacted bans or restrictions on the sale of flavored vapes.

“It’s new, and it’s just been marketed in a way that we’re really fighting the false narrative put out there by makers of these products that are trying to make them appealing to kids,” said Rachel Boykan, MD, clinical professor of pediatrics and attending physician at Stony Brook (N.Y.) Children’s Hospital.

The flavor Red Bull, in particular, hooked Jake. And though he wasn’t aware of it at the time, nicotine packed into the pods may have kept him from quitting: The average nicotine concentration in e-cigarettes more than doubled from 2013 to 2018, according to a study by the Truth Initiative and the CDC.

The immediate risks of nicotine on the developing brain are well documented. Studies suggest that nicotine – which is found in ENDS products – may affect adolescents’ ability to learn, remember, and maintain attention.

But many adolescents and young adults who use e-cigarettes say that vaping helps alleviate anxiety and keep them attentive, which adds to the complexity of their dependency, according to Dr. Boykan.

Nicotine “actually interrupts neural circuits, that it can be associated with more anxiety, depression, attention to learning, and susceptibility to other addictive substances,” she said. “That is enough to make it very scary.”

Jake also said a social environment in which so many of his friends vaped also made it difficult for him to quit.

“You’re hanging out with your friends at night, and all of them are using it, and you’re trying not to,” he said.

Jake eventually took a semester off from college for an unrelated surgery. He moved home, away from his vaping classmates. He eventually transferred to a different college and lived at home, where no one vaped and where he wasn’t allowed to smoke in the house, he said.

“He came home and we took him to a doctor, and they didn’t know quite how to handle kids and addiction to e-cigarettes,” Mrs. Warn said.

Not fully understanding the long-term health implications of e-cigarette use has precluded many clinicians from offering clear messaging on the risk of vaping to current and potential users.

“It’s taken pediatricians time to ask the right questions and recognize nicotine addiction” from vaping, said Dr. Boykan, who serves as chair of the Section on Nicotine and Tobacco Prevention and Treatment of the American Academy of Pediatrics. “It’s just hit us so fast.”

But once pediatricians do identify a nicotine dependency, it can be difficult to treat, Dr. Boykan said. Many pediatricians now recognize that e-cigarette addiction may occur in children as early as middle school.

“We don’t have a lot of evidence-based treatments for kids to recommend,” Dr. Boykan said.
 

Will vaping be a ‘phase?’

Aware of his vaping dependency and the possible risks to his long-term health, Jake, now 23, said he’s lessened his use, compared with his college days, but still struggles to kick the habit for good.

“I’d like to not be able to use all the time, not to feel the urge,” Jake said. “But I think over time it’ll just kind of phase out.”

But his mother said quitting may not be that simple.

“This will be a lifelong journey,” she said. “When I think of who he is, addiction is something he will always have. It’s a part of him now.”

Dr. Boykan, Ms. Schneider, and Dr. Nardis reported no relevant financial disclosures.

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

Jake Warn calls vaping “a toxic artificial love.”

Jake, of Winslow, Maine, was 16 years old when he began vaping. Unlike cigarettes, vaping can be odorless, and its smoke leaves no trace, which allowed him and his friends to use the devices in school bathrooms without fear of being caught.

He would use an entire cartridge containing the vape liquid, the equivalent of smoking one pack of tobacco cigarettes, within 1 school day. By the fall semester of his first year in college, Jake said his use had increased even more.

“It got pricey, so that’s when I really started to notice” the extent of his dependency, he said recently.

Vaping rates among teenagers in Maine doubled from 15.3% to 28.7% between 2017 and 2019, while Jake was in high school. In 2021, 11% of high schoolers across the nation said they regularly smoked e-cigarettes, and an estimated 28% have ever tried the devices, according to the Centers for Disease Control and Prevention.

The Food and Drug Administration classifies e-cigarettes as a tobacco product because many contain nicotine, which comes from tobacco. Like Jake, the habit is likely to carry into adulthood for many who start in their teenage years, experts say.

Electronic nicotine delivery systems (ENDS) such as vapes have been touted by their manufacturers and by some in the medical field as a healthier alternative to cigarettes and as a method to help smokers give up the habit.

But, that’s not how Jake – who had never used combustible cigarettes – picked up vaping, or how he sold the idea to his mother.

“It’s all organic and natural flavoring, it’s just flavored water,” Mary Lou Warn recalled her son saying to her. She researched the health effects of vaping but didn’t find much online. “I knew they were dangerous because you don’t put anything in your lungs that isn’t fresh air.”

A determined athlete in high school, Jake found that his asthma worsened as he transitioned to college, especially when he ran a track meet or during a soccer game.

Mrs. Warn noticed changes off the field, too.

“He was coughing constantly, he wasn’t sleeping well, he wasn’t eating well,” she said. “I knew the addiction was taking over.”

Vaping irritated Jake’s throat, and he would get nosebleeds that he couldn’t stop, she added.

Since Mrs. Warn first looked into the effects of e-cigarettes on respiratory health back in 2017, many studies have been conducted of the short-term health outcomes for first-time smokers who never used combustible tobacco products. Studies suggest that vaping may worsen bronchitis and asthma, raise blood pressure, interfere with brain development in young users, suppress the immune system, and increase the risk of developing a chronic lung disease (Am J Prev Med. 2020 Feb;58[2]:182-90). Studies of mice and cell cultures have found that the vapor or extracts from vapes damage the chemical structure of DNA.

Still, the limited number of long-term human studies has made it hard to know what the health outcomes of e-cigarette users will be in the future. Conclusive studies linking commercial cigarette use to deaths from heart disease and cancer didn’t emerge until the mid-1950s, decades after manufacturers began mass production and marketing in the early 20th century.

Years could pass before researchers gain a clearer understanding of the health implications of long-term e-cigarette use, according to Nigar Nargis, PhD, senior scientific director of tobacco control research at the American Cancer Society.

“There hasn’t been any such study to establish the direct link from ENDS to cancer, but it is understood that it [vaping] may promote the development of cancer and lung damage and inflammation,” Dr. Nargis said.

For decades, advocates built awareness of the harms of tobacco use, which led to a sharp decline in tobacco-related illnesses such as lung cancer. But Hilary Schneider, Maine’s director of government relations for the ACS Cancer Action Network, said she fears the uptick in the use of vapes – especially among those who never smoked or those who use both combustible cigarettes and e-cigarettes – may reverse declines in the rates of smoking-relating diseases.

Multiple studies suggest that inhaling chemicals found in e-cigarettes – including nicotine-carrying aerosols – can damage arteries and inflame and injure the lungs.

Vapes “basically have created a pediatric tobacco-use epidemic,” Ms. Schneider said. “What we’re seeing is unprecedented tobacco use rates, higher rates than we’ve seen in decades.”

One reason many young people start vaping is the attraction to flavors, which range from classic menthol to fruits and sweets. A handful of states have enacted bans or restrictions on the sale of flavored vapes.

“It’s new, and it’s just been marketed in a way that we’re really fighting the false narrative put out there by makers of these products that are trying to make them appealing to kids,” said Rachel Boykan, MD, clinical professor of pediatrics and attending physician at Stony Brook (N.Y.) Children’s Hospital.

The flavor Red Bull, in particular, hooked Jake. And though he wasn’t aware of it at the time, nicotine packed into the pods may have kept him from quitting: The average nicotine concentration in e-cigarettes more than doubled from 2013 to 2018, according to a study by the Truth Initiative and the CDC.

The immediate risks of nicotine on the developing brain are well documented. Studies suggest that nicotine – which is found in ENDS products – may affect adolescents’ ability to learn, remember, and maintain attention.

But many adolescents and young adults who use e-cigarettes say that vaping helps alleviate anxiety and keep them attentive, which adds to the complexity of their dependency, according to Dr. Boykan.

Nicotine “actually interrupts neural circuits, that it can be associated with more anxiety, depression, attention to learning, and susceptibility to other addictive substances,” she said. “That is enough to make it very scary.”

Jake also said a social environment in which so many of his friends vaped also made it difficult for him to quit.

“You’re hanging out with your friends at night, and all of them are using it, and you’re trying not to,” he said.

Jake eventually took a semester off from college for an unrelated surgery. He moved home, away from his vaping classmates. He eventually transferred to a different college and lived at home, where no one vaped and where he wasn’t allowed to smoke in the house, he said.

“He came home and we took him to a doctor, and they didn’t know quite how to handle kids and addiction to e-cigarettes,” Mrs. Warn said.

Not fully understanding the long-term health implications of e-cigarette use has precluded many clinicians from offering clear messaging on the risk of vaping to current and potential users.

“It’s taken pediatricians time to ask the right questions and recognize nicotine addiction” from vaping, said Dr. Boykan, who serves as chair of the Section on Nicotine and Tobacco Prevention and Treatment of the American Academy of Pediatrics. “It’s just hit us so fast.”

But once pediatricians do identify a nicotine dependency, it can be difficult to treat, Dr. Boykan said. Many pediatricians now recognize that e-cigarette addiction may occur in children as early as middle school.

“We don’t have a lot of evidence-based treatments for kids to recommend,” Dr. Boykan said.
 

Will vaping be a ‘phase?’

Aware of his vaping dependency and the possible risks to his long-term health, Jake, now 23, said he’s lessened his use, compared with his college days, but still struggles to kick the habit for good.

“I’d like to not be able to use all the time, not to feel the urge,” Jake said. “But I think over time it’ll just kind of phase out.”

But his mother said quitting may not be that simple.

“This will be a lifelong journey,” she said. “When I think of who he is, addiction is something he will always have. It’s a part of him now.”

Dr. Boykan, Ms. Schneider, and Dr. Nardis reported no relevant financial disclosures.

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

Jake Warn calls vaping “a toxic artificial love.”

Jake, of Winslow, Maine, was 16 years old when he began vaping. Unlike cigarettes, vaping can be odorless, and its smoke leaves no trace, which allowed him and his friends to use the devices in school bathrooms without fear of being caught.

He would use an entire cartridge containing the vape liquid, the equivalent of smoking one pack of tobacco cigarettes, within 1 school day. By the fall semester of his first year in college, Jake said his use had increased even more.

“It got pricey, so that’s when I really started to notice” the extent of his dependency, he said recently.

Vaping rates among teenagers in Maine doubled from 15.3% to 28.7% between 2017 and 2019, while Jake was in high school. In 2021, 11% of high schoolers across the nation said they regularly smoked e-cigarettes, and an estimated 28% have ever tried the devices, according to the Centers for Disease Control and Prevention.

The Food and Drug Administration classifies e-cigarettes as a tobacco product because many contain nicotine, which comes from tobacco. Like Jake, the habit is likely to carry into adulthood for many who start in their teenage years, experts say.

Electronic nicotine delivery systems (ENDS) such as vapes have been touted by their manufacturers and by some in the medical field as a healthier alternative to cigarettes and as a method to help smokers give up the habit.

But, that’s not how Jake – who had never used combustible cigarettes – picked up vaping, or how he sold the idea to his mother.

“It’s all organic and natural flavoring, it’s just flavored water,” Mary Lou Warn recalled her son saying to her. She researched the health effects of vaping but didn’t find much online. “I knew they were dangerous because you don’t put anything in your lungs that isn’t fresh air.”

A determined athlete in high school, Jake found that his asthma worsened as he transitioned to college, especially when he ran a track meet or during a soccer game.

Mrs. Warn noticed changes off the field, too.

“He was coughing constantly, he wasn’t sleeping well, he wasn’t eating well,” she said. “I knew the addiction was taking over.”

Vaping irritated Jake’s throat, and he would get nosebleeds that he couldn’t stop, she added.

Since Mrs. Warn first looked into the effects of e-cigarettes on respiratory health back in 2017, many studies have been conducted of the short-term health outcomes for first-time smokers who never used combustible tobacco products. Studies suggest that vaping may worsen bronchitis and asthma, raise blood pressure, interfere with brain development in young users, suppress the immune system, and increase the risk of developing a chronic lung disease (Am J Prev Med. 2020 Feb;58[2]:182-90). Studies of mice and cell cultures have found that the vapor or extracts from vapes damage the chemical structure of DNA.

Still, the limited number of long-term human studies has made it hard to know what the health outcomes of e-cigarette users will be in the future. Conclusive studies linking commercial cigarette use to deaths from heart disease and cancer didn’t emerge until the mid-1950s, decades after manufacturers began mass production and marketing in the early 20th century.

Years could pass before researchers gain a clearer understanding of the health implications of long-term e-cigarette use, according to Nigar Nargis, PhD, senior scientific director of tobacco control research at the American Cancer Society.

“There hasn’t been any such study to establish the direct link from ENDS to cancer, but it is understood that it [vaping] may promote the development of cancer and lung damage and inflammation,” Dr. Nargis said.

For decades, advocates built awareness of the harms of tobacco use, which led to a sharp decline in tobacco-related illnesses such as lung cancer. But Hilary Schneider, Maine’s director of government relations for the ACS Cancer Action Network, said she fears the uptick in the use of vapes – especially among those who never smoked or those who use both combustible cigarettes and e-cigarettes – may reverse declines in the rates of smoking-relating diseases.

Multiple studies suggest that inhaling chemicals found in e-cigarettes – including nicotine-carrying aerosols – can damage arteries and inflame and injure the lungs.

Vapes “basically have created a pediatric tobacco-use epidemic,” Ms. Schneider said. “What we’re seeing is unprecedented tobacco use rates, higher rates than we’ve seen in decades.”

One reason many young people start vaping is the attraction to flavors, which range from classic menthol to fruits and sweets. A handful of states have enacted bans or restrictions on the sale of flavored vapes.

“It’s new, and it’s just been marketed in a way that we’re really fighting the false narrative put out there by makers of these products that are trying to make them appealing to kids,” said Rachel Boykan, MD, clinical professor of pediatrics and attending physician at Stony Brook (N.Y.) Children’s Hospital.

The flavor Red Bull, in particular, hooked Jake. And though he wasn’t aware of it at the time, nicotine packed into the pods may have kept him from quitting: The average nicotine concentration in e-cigarettes more than doubled from 2013 to 2018, according to a study by the Truth Initiative and the CDC.

The immediate risks of nicotine on the developing brain are well documented. Studies suggest that nicotine – which is found in ENDS products – may affect adolescents’ ability to learn, remember, and maintain attention.

But many adolescents and young adults who use e-cigarettes say that vaping helps alleviate anxiety and keep them attentive, which adds to the complexity of their dependency, according to Dr. Boykan.

Nicotine “actually interrupts neural circuits, that it can be associated with more anxiety, depression, attention to learning, and susceptibility to other addictive substances,” she said. “That is enough to make it very scary.”

Jake also said a social environment in which so many of his friends vaped also made it difficult for him to quit.

“You’re hanging out with your friends at night, and all of them are using it, and you’re trying not to,” he said.

Jake eventually took a semester off from college for an unrelated surgery. He moved home, away from his vaping classmates. He eventually transferred to a different college and lived at home, where no one vaped and where he wasn’t allowed to smoke in the house, he said.

“He came home and we took him to a doctor, and they didn’t know quite how to handle kids and addiction to e-cigarettes,” Mrs. Warn said.

Not fully understanding the long-term health implications of e-cigarette use has precluded many clinicians from offering clear messaging on the risk of vaping to current and potential users.

“It’s taken pediatricians time to ask the right questions and recognize nicotine addiction” from vaping, said Dr. Boykan, who serves as chair of the Section on Nicotine and Tobacco Prevention and Treatment of the American Academy of Pediatrics. “It’s just hit us so fast.”

But once pediatricians do identify a nicotine dependency, it can be difficult to treat, Dr. Boykan said. Many pediatricians now recognize that e-cigarette addiction may occur in children as early as middle school.

“We don’t have a lot of evidence-based treatments for kids to recommend,” Dr. Boykan said.
 

Will vaping be a ‘phase?’

Aware of his vaping dependency and the possible risks to his long-term health, Jake, now 23, said he’s lessened his use, compared with his college days, but still struggles to kick the habit for good.

“I’d like to not be able to use all the time, not to feel the urge,” Jake said. “But I think over time it’ll just kind of phase out.”

But his mother said quitting may not be that simple.

“This will be a lifelong journey,” she said. “When I think of who he is, addiction is something he will always have. It’s a part of him now.”

Dr. Boykan, Ms. Schneider, and Dr. Nardis reported no relevant financial disclosures.

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

A new report offers more insight into the connection between cumulative smoking levels and lung cancer.

People who have smoked an average of 1 pack a day for 20-39 years tripled their tumor risk versus less-heavy smokers and 30-fold versus those who never smoked. For those who smoked the equivalent of 1 pack for 40-60 years, or 2 packs for 20-30 years, the risk levels grew by fourfold and 40-fold, respectively. For those who’ve smoked even more, the likelihood of developing lung cancer is high, but the risk remains stable and doesn’t grow more over time, according to the analysis.

The report, released at the annual European Lung Cancer Congress 2023 meeting, and an earlier related study “underscore the importance of smoking abstinence and early smoking cessation,” said study lead author J. Anthony Nations, MD, MBA, in an interview.

The earlier study, published in JAMA Oncology, relied on a “pack-year” analysis to evaluate the risk of lung cancer in smokers. A pack-year refers to the cigarette use of a person who smoked a pack a day for 1 year. It’s the equivalent of smoking half a pack for 2 years or 2 packs for 6 months.

By this measure, a smoker with 20 pack-years of cigarette use smoked the equivalent of a pack a day for 20 years or 2 packs a day for 10 years. U.S. guidelines recommend annual low-dose CT lung cancer screening in adults who are aged 50-80, have more than 20 pack-years of tobacco exposure, and either currently smoke or quit within the last 15 years.

The JAMA Oncology report “showed that, compared with never-smokers, current heavy and nonheavy smokers had [a] 40 and 10 times higher risk of lung cancer, respectively,” said Dr. Nations, who is also a pulmonologist with Washington D.C. Veterans Affairs Medical Center. “A smoking history of greater than 20 pack-years was considered heavy, but current heavy smokers had a median pack-year smoking history of 50 pack-years. This observation prompted us to want to look more closely at pack-year smoking history.”

For the new analysis, researchers tracked 2,505 older adults (mean age, 73 ± 5.7 years; 69% women, 17% African American) in the Cardiovascular Health Study. Of those, 532 were current smokers (18% less than 20 pack-years, 30% 20-39 pack-years, 34% 40–59 pack-years, and 18% greater than 60 pack-years).

Lung cancer occurred in 0.5% of those who never smoked, 5% of those who smoked less than 20 pack-years, 14.6% of those who smoked 20-39 pack-years, 17.7% of those who smoked 40-59 pack-years, and 16.0% for those who smoked more than 60 pack-years. In an analysis adjusted for age, sex, race, and competing risk of death, researchers found that those who smoked less than 20 pack-years were 9.73 times more likely to develop lung cancer than those who never smoked (hazard ratio, 9.73). The HRs of lung cancer versus never-smokers for the other groups were 30.33 (20-39 pack-years), 42.97 (40-59 pack-years), and 46.02 (greater than 60 pack-years.).

“While it was not surprising that the risk of lung cancer in current heavy smokers would be proportionately greater in smokers with higher pack-year smoking history, we were surprised to see that the risk almost plateaued in the heaviest current smokers,” Dr. Nations said.

As for the clinical message from the findings, Dr. Nations said they reveal that quitting smoking makes a difference in lung cancer risk, even after many years of heavy smoking. “Smokers who quit after a 30–pack-year smoking history will not incur the higher risk of those with a 40– or 50–pack-year smoking history.”

The previous JAMA Oncology paper also showed that quitting pays dividends by reducing lung cancer risk. Subjects with at least 20 pack-years of smoking who quit less than 15 years ago nearly halved their excess risk of lung cancer, compared with similar current smokers who didn’t quit.

In an interview, cancer researcher Robert J. Volk, PhD, of the University of Texas MD Anderson Cancer Center, Houston, praised the new analysis but noted that it has limitations: “The sample is fairly small – 532 adults who currently smoke – and the subgroups based on pack-years are even smaller.”

No study funding is reported. The study authors and Dr. Volk reported no disclosures.

*This article was updated on 4/17/23.

A new report offers more insight into the connection between cumulative smoking levels and lung cancer.

People who have smoked an average of 1 pack a day for 20-39 years tripled their tumor risk versus less-heavy smokers and 30-fold versus those who never smoked. For those who smoked the equivalent of 1 pack for 40-60 years, or 2 packs for 20-30 years, the risk levels grew by fourfold and 40-fold, respectively. For those who’ve smoked even more, the likelihood of developing lung cancer is high, but the risk remains stable and doesn’t grow more over time, according to the analysis.

The report, released at the annual European Lung Cancer Congress 2023 meeting, and an earlier related study “underscore the importance of smoking abstinence and early smoking cessation,” said study lead author J. Anthony Nations, MD, MBA, in an interview.

The earlier study, published in JAMA Oncology, relied on a “pack-year” analysis to evaluate the risk of lung cancer in smokers. A pack-year refers to the cigarette use of a person who smoked a pack a day for 1 year. It’s the equivalent of smoking half a pack for 2 years or 2 packs for 6 months.

By this measure, a smoker with 20 pack-years of cigarette use smoked the equivalent of a pack a day for 20 years or 2 packs a day for 10 years. U.S. guidelines recommend annual low-dose CT lung cancer screening in adults who are aged 50-80, have more than 20 pack-years of tobacco exposure, and either currently smoke or quit within the last 15 years.

The JAMA Oncology report “showed that, compared with never-smokers, current heavy and nonheavy smokers had [a] 40 and 10 times higher risk of lung cancer, respectively,” said Dr. Nations, who is also a pulmonologist with Washington D.C. Veterans Affairs Medical Center. “A smoking history of greater than 20 pack-years was considered heavy, but current heavy smokers had a median pack-year smoking history of 50 pack-years. This observation prompted us to want to look more closely at pack-year smoking history.”

For the new analysis, researchers tracked 2,505 older adults (mean age, 73 ± 5.7 years; 69% women, 17% African American) in the Cardiovascular Health Study. Of those, 532 were current smokers (18% less than 20 pack-years, 30% 20-39 pack-years, 34% 40–59 pack-years, and 18% greater than 60 pack-years).

Lung cancer occurred in 0.5% of those who never smoked, 5% of those who smoked less than 20 pack-years, 14.6% of those who smoked 20-39 pack-years, 17.7% of those who smoked 40-59 pack-years, and 16.0% for those who smoked more than 60 pack-years. In an analysis adjusted for age, sex, race, and competing risk of death, researchers found that those who smoked less than 20 pack-years were 9.73 times more likely to develop lung cancer than those who never smoked (hazard ratio, 9.73). The HRs of lung cancer versus never-smokers for the other groups were 30.33 (20-39 pack-years), 42.97 (40-59 pack-years), and 46.02 (greater than 60 pack-years.).

“While it was not surprising that the risk of lung cancer in current heavy smokers would be proportionately greater in smokers with higher pack-year smoking history, we were surprised to see that the risk almost plateaued in the heaviest current smokers,” Dr. Nations said.

As for the clinical message from the findings, Dr. Nations said they reveal that quitting smoking makes a difference in lung cancer risk, even after many years of heavy smoking. “Smokers who quit after a 30–pack-year smoking history will not incur the higher risk of those with a 40– or 50–pack-year smoking history.”

The previous JAMA Oncology paper also showed that quitting pays dividends by reducing lung cancer risk. Subjects with at least 20 pack-years of smoking who quit less than 15 years ago nearly halved their excess risk of lung cancer, compared with similar current smokers who didn’t quit.

In an interview, cancer researcher Robert J. Volk, PhD, of the University of Texas MD Anderson Cancer Center, Houston, praised the new analysis but noted that it has limitations: “The sample is fairly small – 532 adults who currently smoke – and the subgroups based on pack-years are even smaller.”

No study funding is reported. The study authors and Dr. Volk reported no disclosures.

*This article was updated on 4/17/23.

A new report offers more insight into the connection between cumulative smoking levels and lung cancer.

People who have smoked an average of 1 pack a day for 20-39 years tripled their tumor risk versus less-heavy smokers and 30-fold versus those who never smoked. For those who smoked the equivalent of 1 pack for 40-60 years, or 2 packs for 20-30 years, the risk levels grew by fourfold and 40-fold, respectively. For those who’ve smoked even more, the likelihood of developing lung cancer is high, but the risk remains stable and doesn’t grow more over time, according to the analysis.

The report, released at the annual European Lung Cancer Congress 2023 meeting, and an earlier related study “underscore the importance of smoking abstinence and early smoking cessation,” said study lead author J. Anthony Nations, MD, MBA, in an interview.

The earlier study, published in JAMA Oncology, relied on a “pack-year” analysis to evaluate the risk of lung cancer in smokers. A pack-year refers to the cigarette use of a person who smoked a pack a day for 1 year. It’s the equivalent of smoking half a pack for 2 years or 2 packs for 6 months.

By this measure, a smoker with 20 pack-years of cigarette use smoked the equivalent of a pack a day for 20 years or 2 packs a day for 10 years. U.S. guidelines recommend annual low-dose CT lung cancer screening in adults who are aged 50-80, have more than 20 pack-years of tobacco exposure, and either currently smoke or quit within the last 15 years.

The JAMA Oncology report “showed that, compared with never-smokers, current heavy and nonheavy smokers had [a] 40 and 10 times higher risk of lung cancer, respectively,” said Dr. Nations, who is also a pulmonologist with Washington D.C. Veterans Affairs Medical Center. “A smoking history of greater than 20 pack-years was considered heavy, but current heavy smokers had a median pack-year smoking history of 50 pack-years. This observation prompted us to want to look more closely at pack-year smoking history.”

For the new analysis, researchers tracked 2,505 older adults (mean age, 73 ± 5.7 years; 69% women, 17% African American) in the Cardiovascular Health Study. Of those, 532 were current smokers (18% less than 20 pack-years, 30% 20-39 pack-years, 34% 40–59 pack-years, and 18% greater than 60 pack-years).

Lung cancer occurred in 0.5% of those who never smoked, 5% of those who smoked less than 20 pack-years, 14.6% of those who smoked 20-39 pack-years, 17.7% of those who smoked 40-59 pack-years, and 16.0% for those who smoked more than 60 pack-years. In an analysis adjusted for age, sex, race, and competing risk of death, researchers found that those who smoked less than 20 pack-years were 9.73 times more likely to develop lung cancer than those who never smoked (hazard ratio, 9.73). The HRs of lung cancer versus never-smokers for the other groups were 30.33 (20-39 pack-years), 42.97 (40-59 pack-years), and 46.02 (greater than 60 pack-years.).

“While it was not surprising that the risk of lung cancer in current heavy smokers would be proportionately greater in smokers with higher pack-year smoking history, we were surprised to see that the risk almost plateaued in the heaviest current smokers,” Dr. Nations said.

As for the clinical message from the findings, Dr. Nations said they reveal that quitting smoking makes a difference in lung cancer risk, even after many years of heavy smoking. “Smokers who quit after a 30–pack-year smoking history will not incur the higher risk of those with a 40– or 50–pack-year smoking history.”

The previous JAMA Oncology paper also showed that quitting pays dividends by reducing lung cancer risk. Subjects with at least 20 pack-years of smoking who quit less than 15 years ago nearly halved their excess risk of lung cancer, compared with similar current smokers who didn’t quit.

In an interview, cancer researcher Robert J. Volk, PhD, of the University of Texas MD Anderson Cancer Center, Houston, praised the new analysis but noted that it has limitations: “The sample is fairly small – 532 adults who currently smoke – and the subgroups based on pack-years are even smaller.”

No study funding is reported. The study authors and Dr. Volk reported no disclosures.

*This article was updated on 4/17/23.