Nicholas E. Ghionni, DO

CHEST

Evidence-based medicine (EBM) stems from making the best patient-centered decision from the highest-quality data available that comports with our understanding of pathophysiology. In some situations, clinicians are forced to draw conclusions from data that are imperfect and apply it to patients who are complex and dynamic. For most pathologies, available data provides some direction. There is, however, one pathophysiologic state that remains understudied, precarious, and common.

The Centers for Disease Control and Prevention (CDC) estimates that about 7.7% of the United States population has asthma. There were about 1 million ED visits in 2020, with asthma listed as the primary diagnosis, and only 94,000 required hospitalization.¹ There are many tools we employ that have greatly decreased inpatient admissions for asthma. The uptake of inhaled corticosteroids (ICS) has significantly reduced asthma-related morbidity and mortality and reduced exacerbations that require admission to a hospital. This treatment strategy is supported by the Global Initiative for Asthma (GINA) and National Asthma Education and Prevention Program (NAEPP) guidelines.^2,3 While we should celebrate the impact that EBM and ICS have had on asthma outcomes, we continue to struggle to control severe asthma.

Bronchodilator therapy in the hospital is ubiquitous. House staff and hospitalists click the bronchodilator order set early and often. However, the optimal frequency, dose, and duration of inhaled bronchodilator therapy for acute asthma exacerbation are unknown. Do frequency, dose, and duration change with exacerbation severity? Nothing gets ED, inpatient, or ICU physicians more jittery than the phrase “exacerbation of asthma on BiPap” or “intubated for asthma.” With its enormous clinical impact and notoriously difficult hospital and ICU course, the lack of evidence we have for managing these patients outside of the initial 24- to 48-hour visit is concerning. Neither NAEPP nor GINA provide management recommendations for the patient with severe asthma exacerbation that necessitates admission.

Albuterol is a commonly used medication for asthma and chronic obstructive airway disease. It is rapid acting and effective—few medications give patients (or clinicians) such instant satisfaction. As an internal medicine resident and pulmonary fellow, I ordered it countless times without ever looking at the dose. Sometimes, patients would come up from the emergency department after receiving a “continuous dose.” I would often wonder exactly what that meant. After some investigation, I found that in my hospital at the time, one dose of albuterol was 2.5 mg in 2 mL, and a continuous nebulization was four doses for a total of 10 mg.

Shrestha et al. found that high-dose albuterol (7.5 mg) administered continuously was superior to 2.5 mg albuterol delivered three times over 1.5 hours. There were demonstrable improvements in FEV₁ and no ICU admissions.⁴ This study is one of many that compared intermittent to continuous and high-dose vs low-dose albuterol in the emergency department. Most are small and occur over the first 24 hours of presentation to the hospital. They often use short-term changes in spirometry as their primary outcome measure. Being a pulmonary and critical care doctor, I see patients who require advanced rescue maneuvers such as noninvasive positive pressure ventilation (NIPPV) or other pharmacologic adjuncts, for which the current evidence is limited.

Because studies of inhaled bronchodilators in acute asthma exacerbation use spirometry as their primary outcome, those with more severe disease and higher acuity are excluded. Patients on NIPPV can’t perform spirometry. There is essentially no literature to guide treatment for a patient with asthma in the adult ICU. In pediatric intensive care units, there are some data to support either continuous or intermittent inhaled bronchodilator that extends beyond the initial ED visit up to about 60 hours.⁵ Much of the pediatric data revolve about the amount of albuterol given, which can be as high as 75 mg/hr though is typically closer to 10-20 mg/hr.⁶ This rate is continued until respiratory improvement occurs.

With poor evidence to guide us and no specific direction from major guidelines, how should providers manage severe asthma exacerbation? The amount of drug deposited in the lung varies by the device used to deliver it. For nebulization, only about 10% of the nebulized amount reaches the lungs for effect; this is a smaller amount compared with all other devices one could use, such as MDI or DPI.⁷ Once a patient with asthma reaches the emergency department, that person is usually placed on some form of nebulizer treatment. But based on local hospital protocols, the amount and duration can vary widely. Sometimes, in patients with severe exacerbation, there is trepidation to continuing albuterol therapy due to ongoing tachycardia. This seems reasonable given increased albuterol administration could beget an ongoing cycle of dyspnea and anxiety. It could also lead to choosing therapies that are less evidence based.

In closing, this seemingly mundane topic takes on new meaning when a patient is in severe exacerbation. Fortunately, providers are not often faced with the decision to wade into the evidence-free territory of severe asthma exacerbation that is unresponsive to first-line treatments. This narrative should serve as a general alert that this pathophysiologic state is understudied. When encountered, thoughtful consideration of pathology, physiology, and pharmacology is required to reverse it.

References

1. Centers for Disease Control and Prevention. (2023, May 10). Most recent national asthma data. Centers for Disease Control and Prevention. https://www.cdc.gov/asthma/most_recent_national_asthma_data.htm

2. Global Initiative for Asthma - GINA. (2023, August 15). 2023 GINA Main Report - Global Initiative for Asthma - GINA. https://ginasthma.org/2023-gina-main-report/

3. Kiley J, Mensah GA, Boyce CA, et al (A Report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group). 2020 Focused updates to the: Asthma Management Guidelines. US Department of Health and Human Services, NIH, NHLBI 2020.

4. Shrestha M, Bidadi K, Gourlay S, Hayes J. Continuous vs intermittent albuterol, at high and low doses, in the treatment of severe acute asthma in adults. Chest. 1996 Jul;110(1):42-7. doi: 10.1378/chest.110.1.42. PMID: 8681661.

5. Kulalert P, Phinyo P, Patumanond J, Smathakanee C, Chuenjit W, Nanthapisal S. Continuous versus intermittent short-acting β2-agonists nebulization as first-line therapy in hospitalized children with severe asthma exacerbation: a propensity score matching analysis. Asthma Res Pract. 2020 Jul 2;6:6. doi: 10.1186/s40733-020-00059-5. PMID: 32632352; PMCID: PMC7329360.

6. Phumeetham S, Bahk TJ, Abd-Allah S, Mathur M. Effect of high-dose continuous albuterol nebulization on clinical variables in children with status asthmaticus. Pediatr Crit Care Med. 2015 Feb;16(2):e41-6. doi: 10.1097/PCC.0000000000000314. PMID: 25560428.

7. Gardenhire DS, Burnett D, Strickland S, Myers, TR. A guide to aerosol delivery devices for respiratory therapists. American Association for Respiratory Care, Dallas, Texas 2017.

CHEST

Evidence-based medicine (EBM) stems from making the best patient-centered decision from the highest-quality data available that comports with our understanding of pathophysiology. In some situations, clinicians are forced to draw conclusions from data that are imperfect and apply it to patients who are complex and dynamic. For most pathologies, available data provides some direction. There is, however, one pathophysiologic state that remains understudied, precarious, and common.

The Centers for Disease Control and Prevention (CDC) estimates that about 7.7% of the United States population has asthma. There were about 1 million ED visits in 2020, with asthma listed as the primary diagnosis, and only 94,000 required hospitalization.¹ There are many tools we employ that have greatly decreased inpatient admissions for asthma. The uptake of inhaled corticosteroids (ICS) has significantly reduced asthma-related morbidity and mortality and reduced exacerbations that require admission to a hospital. This treatment strategy is supported by the Global Initiative for Asthma (GINA) and National Asthma Education and Prevention Program (NAEPP) guidelines.^2,3 While we should celebrate the impact that EBM and ICS have had on asthma outcomes, we continue to struggle to control severe asthma.

Bronchodilator therapy in the hospital is ubiquitous. House staff and hospitalists click the bronchodilator order set early and often. However, the optimal frequency, dose, and duration of inhaled bronchodilator therapy for acute asthma exacerbation are unknown. Do frequency, dose, and duration change with exacerbation severity? Nothing gets ED, inpatient, or ICU physicians more jittery than the phrase “exacerbation of asthma on BiPap” or “intubated for asthma.” With its enormous clinical impact and notoriously difficult hospital and ICU course, the lack of evidence we have for managing these patients outside of the initial 24- to 48-hour visit is concerning. Neither NAEPP nor GINA provide management recommendations for the patient with severe asthma exacerbation that necessitates admission.

Albuterol is a commonly used medication for asthma and chronic obstructive airway disease. It is rapid acting and effective—few medications give patients (or clinicians) such instant satisfaction. As an internal medicine resident and pulmonary fellow, I ordered it countless times without ever looking at the dose. Sometimes, patients would come up from the emergency department after receiving a “continuous dose.” I would often wonder exactly what that meant. After some investigation, I found that in my hospital at the time, one dose of albuterol was 2.5 mg in 2 mL, and a continuous nebulization was four doses for a total of 10 mg.

Shrestha et al. found that high-dose albuterol (7.5 mg) administered continuously was superior to 2.5 mg albuterol delivered three times over 1.5 hours. There were demonstrable improvements in FEV₁ and no ICU admissions.⁴ This study is one of many that compared intermittent to continuous and high-dose vs low-dose albuterol in the emergency department. Most are small and occur over the first 24 hours of presentation to the hospital. They often use short-term changes in spirometry as their primary outcome measure. Being a pulmonary and critical care doctor, I see patients who require advanced rescue maneuvers such as noninvasive positive pressure ventilation (NIPPV) or other pharmacologic adjuncts, for which the current evidence is limited.

Because studies of inhaled bronchodilators in acute asthma exacerbation use spirometry as their primary outcome, those with more severe disease and higher acuity are excluded. Patients on NIPPV can’t perform spirometry. There is essentially no literature to guide treatment for a patient with asthma in the adult ICU. In pediatric intensive care units, there are some data to support either continuous or intermittent inhaled bronchodilator that extends beyond the initial ED visit up to about 60 hours.⁵ Much of the pediatric data revolve about the amount of albuterol given, which can be as high as 75 mg/hr though is typically closer to 10-20 mg/hr.⁶ This rate is continued until respiratory improvement occurs.

With poor evidence to guide us and no specific direction from major guidelines, how should providers manage severe asthma exacerbation? The amount of drug deposited in the lung varies by the device used to deliver it. For nebulization, only about 10% of the nebulized amount reaches the lungs for effect; this is a smaller amount compared with all other devices one could use, such as MDI or DPI.⁷ Once a patient with asthma reaches the emergency department, that person is usually placed on some form of nebulizer treatment. But based on local hospital protocols, the amount and duration can vary widely. Sometimes, in patients with severe exacerbation, there is trepidation to continuing albuterol therapy due to ongoing tachycardia. This seems reasonable given increased albuterol administration could beget an ongoing cycle of dyspnea and anxiety. It could also lead to choosing therapies that are less evidence based.

In closing, this seemingly mundane topic takes on new meaning when a patient is in severe exacerbation. Fortunately, providers are not often faced with the decision to wade into the evidence-free territory of severe asthma exacerbation that is unresponsive to first-line treatments. This narrative should serve as a general alert that this pathophysiologic state is understudied. When encountered, thoughtful consideration of pathology, physiology, and pharmacology is required to reverse it.

References

1. Centers for Disease Control and Prevention. (2023, May 10). Most recent national asthma data. Centers for Disease Control and Prevention. https://www.cdc.gov/asthma/most_recent_national_asthma_data.htm

2. Global Initiative for Asthma - GINA. (2023, August 15). 2023 GINA Main Report - Global Initiative for Asthma - GINA. https://ginasthma.org/2023-gina-main-report/

3. Kiley J, Mensah GA, Boyce CA, et al (A Report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group). 2020 Focused updates to the: Asthma Management Guidelines. US Department of Health and Human Services, NIH, NHLBI 2020.

4. Shrestha M, Bidadi K, Gourlay S, Hayes J. Continuous vs intermittent albuterol, at high and low doses, in the treatment of severe acute asthma in adults. Chest. 1996 Jul;110(1):42-7. doi: 10.1378/chest.110.1.42. PMID: 8681661.

5. Kulalert P, Phinyo P, Patumanond J, Smathakanee C, Chuenjit W, Nanthapisal S. Continuous versus intermittent short-acting β2-agonists nebulization as first-line therapy in hospitalized children with severe asthma exacerbation: a propensity score matching analysis. Asthma Res Pract. 2020 Jul 2;6:6. doi: 10.1186/s40733-020-00059-5. PMID: 32632352; PMCID: PMC7329360.

6. Phumeetham S, Bahk TJ, Abd-Allah S, Mathur M. Effect of high-dose continuous albuterol nebulization on clinical variables in children with status asthmaticus. Pediatr Crit Care Med. 2015 Feb;16(2):e41-6. doi: 10.1097/PCC.0000000000000314. PMID: 25560428.

7. Gardenhire DS, Burnett D, Strickland S, Myers, TR. A guide to aerosol delivery devices for respiratory therapists. American Association for Respiratory Care, Dallas, Texas 2017.

CHEST

Evidence-based medicine (EBM) stems from making the best patient-centered decision from the highest-quality data available that comports with our understanding of pathophysiology. In some situations, clinicians are forced to draw conclusions from data that are imperfect and apply it to patients who are complex and dynamic. For most pathologies, available data provides some direction. There is, however, one pathophysiologic state that remains understudied, precarious, and common.

The Centers for Disease Control and Prevention (CDC) estimates that about 7.7% of the United States population has asthma. There were about 1 million ED visits in 2020, with asthma listed as the primary diagnosis, and only 94,000 required hospitalization.¹ There are many tools we employ that have greatly decreased inpatient admissions for asthma. The uptake of inhaled corticosteroids (ICS) has significantly reduced asthma-related morbidity and mortality and reduced exacerbations that require admission to a hospital. This treatment strategy is supported by the Global Initiative for Asthma (GINA) and National Asthma Education and Prevention Program (NAEPP) guidelines.^2,3 While we should celebrate the impact that EBM and ICS have had on asthma outcomes, we continue to struggle to control severe asthma.

Bronchodilator therapy in the hospital is ubiquitous. House staff and hospitalists click the bronchodilator order set early and often. However, the optimal frequency, dose, and duration of inhaled bronchodilator therapy for acute asthma exacerbation are unknown. Do frequency, dose, and duration change with exacerbation severity? Nothing gets ED, inpatient, or ICU physicians more jittery than the phrase “exacerbation of asthma on BiPap” or “intubated for asthma.” With its enormous clinical impact and notoriously difficult hospital and ICU course, the lack of evidence we have for managing these patients outside of the initial 24- to 48-hour visit is concerning. Neither NAEPP nor GINA provide management recommendations for the patient with severe asthma exacerbation that necessitates admission.

Albuterol is a commonly used medication for asthma and chronic obstructive airway disease. It is rapid acting and effective—few medications give patients (or clinicians) such instant satisfaction. As an internal medicine resident and pulmonary fellow, I ordered it countless times without ever looking at the dose. Sometimes, patients would come up from the emergency department after receiving a “continuous dose.” I would often wonder exactly what that meant. After some investigation, I found that in my hospital at the time, one dose of albuterol was 2.5 mg in 2 mL, and a continuous nebulization was four doses for a total of 10 mg.

Shrestha et al. found that high-dose albuterol (7.5 mg) administered continuously was superior to 2.5 mg albuterol delivered three times over 1.5 hours. There were demonstrable improvements in FEV₁ and no ICU admissions.⁴ This study is one of many that compared intermittent to continuous and high-dose vs low-dose albuterol in the emergency department. Most are small and occur over the first 24 hours of presentation to the hospital. They often use short-term changes in spirometry as their primary outcome measure. Being a pulmonary and critical care doctor, I see patients who require advanced rescue maneuvers such as noninvasive positive pressure ventilation (NIPPV) or other pharmacologic adjuncts, for which the current evidence is limited.

Because studies of inhaled bronchodilators in acute asthma exacerbation use spirometry as their primary outcome, those with more severe disease and higher acuity are excluded. Patients on NIPPV can’t perform spirometry. There is essentially no literature to guide treatment for a patient with asthma in the adult ICU. In pediatric intensive care units, there are some data to support either continuous or intermittent inhaled bronchodilator that extends beyond the initial ED visit up to about 60 hours.⁵ Much of the pediatric data revolve about the amount of albuterol given, which can be as high as 75 mg/hr though is typically closer to 10-20 mg/hr.⁶ This rate is continued until respiratory improvement occurs.

With poor evidence to guide us and no specific direction from major guidelines, how should providers manage severe asthma exacerbation? The amount of drug deposited in the lung varies by the device used to deliver it. For nebulization, only about 10% of the nebulized amount reaches the lungs for effect; this is a smaller amount compared with all other devices one could use, such as MDI or DPI.⁷ Once a patient with asthma reaches the emergency department, that person is usually placed on some form of nebulizer treatment. But based on local hospital protocols, the amount and duration can vary widely. Sometimes, in patients with severe exacerbation, there is trepidation to continuing albuterol therapy due to ongoing tachycardia. This seems reasonable given increased albuterol administration could beget an ongoing cycle of dyspnea and anxiety. It could also lead to choosing therapies that are less evidence based.

In closing, this seemingly mundane topic takes on new meaning when a patient is in severe exacerbation. Fortunately, providers are not often faced with the decision to wade into the evidence-free territory of severe asthma exacerbation that is unresponsive to first-line treatments. This narrative should serve as a general alert that this pathophysiologic state is understudied. When encountered, thoughtful consideration of pathology, physiology, and pharmacology is required to reverse it.

References

1. Centers for Disease Control and Prevention. (2023, May 10). Most recent national asthma data. Centers for Disease Control and Prevention. https://www.cdc.gov/asthma/most_recent_national_asthma_data.htm

2. Global Initiative for Asthma - GINA. (2023, August 15). 2023 GINA Main Report - Global Initiative for Asthma - GINA. https://ginasthma.org/2023-gina-main-report/

3. Kiley J, Mensah GA, Boyce CA, et al (A Report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group). 2020 Focused updates to the: Asthma Management Guidelines. US Department of Health and Human Services, NIH, NHLBI 2020.

4. Shrestha M, Bidadi K, Gourlay S, Hayes J. Continuous vs intermittent albuterol, at high and low doses, in the treatment of severe acute asthma in adults. Chest. 1996 Jul;110(1):42-7. doi: 10.1378/chest.110.1.42. PMID: 8681661.

5. Kulalert P, Phinyo P, Patumanond J, Smathakanee C, Chuenjit W, Nanthapisal S. Continuous versus intermittent short-acting β2-agonists nebulization as first-line therapy in hospitalized children with severe asthma exacerbation: a propensity score matching analysis. Asthma Res Pract. 2020 Jul 2;6:6. doi: 10.1186/s40733-020-00059-5. PMID: 32632352; PMCID: PMC7329360.

6. Phumeetham S, Bahk TJ, Abd-Allah S, Mathur M. Effect of high-dose continuous albuterol nebulization on clinical variables in children with status asthmaticus. Pediatr Crit Care Med. 2015 Feb;16(2):e41-6. doi: 10.1097/PCC.0000000000000314. PMID: 25560428.

7. Gardenhire DS, Burnett D, Strickland S, Myers, TR. A guide to aerosol delivery devices for respiratory therapists. American Association for Respiratory Care, Dallas, Texas 2017.

The European Respiratory Society (ERS) and American Thoracic Society (ATS) just published an update to their guidelines on lung function interpretation (Stanojevic S, et al. Eur Respir J. 2022; 60: 2101499). As with any update, the document builds on past work and integrates new advances the field has seen since 2005.

The current iteration comes at a time when academics, clinicians, and epidemiologists are re-analyzing what we think we know about the complex ways race and ethnicity intersect with the practice of medicine. Several experts on lung function testing, many if not most of whom are authors on the ERS/ATS guideline, have written letters or published reviews commenting on the way accounting for race or ethnicity affects lung function interpretation.

Race/ethnicity and lung function was also the topic of an excellent session at the recent CHEST 2022 Annual Meeting in Nashville, Tennessee. Here, we’ll provide a brief review and direct the reader to relevant sources for a more detailed analysis.

Spirometry is an integral part of the diagnosis and management of a wide range of pulmonary conditions. Dr. Aaron Baugh from the University of California San Francisco (UCSF) lectured on the spirometer’s history at CHEST 2022 and detailed its interactions with race over the past 2 centuries. Other authors have chronicled this history, as well (Braun L, et al. Can J Respir Ther. 2015;51[4]:99-101). The short version is that since the British surgeon John Hutchinson created the first spirometer in 1846, race has been a part of the discussion of lung function interpretation.

In 2022, we know far more about the factors that determine lung function than we did in the 19th century. Age, height, and sex assigned at birth all explain a high percentage of the variability seen in FEV1 and FVC. When modeled, race also explains a portion of the variability, and the NHANES III investigators found its inclusion in regression equations, along with age, height, and sex, improved their precision. Case closed, right? Modern medicine is defined by phenotyping, precision, and individualized care, so why shouldn’t race be a part of lung function interpretation?

Well, it’s complicated. With the increasing recognition of health disparities across racial groups the way race is incorporated in medical practice is understandably being scrutinized. As clinicians and academics, we must analyze the root cause of differences in health outcomes between racial groups.

Publications on pulse oximetry (Gottlieb ER, et al. JAMA Intern Med. 2022; 182:849-858) and glomerular filtration rate (Williams WW, et al. N Engl J Med. 2021;385:1804-1806) have revealed some of the ways our use of instruments and equations may exacerbate or perpetuate current disparities. Even small differences in a measure like pulse oximetry could have a profound impact on clinical decisions at the individual and population levels.

The 2022 ERS/ATS lung function interpretation guidelines have abandoned the use of NHANES III as a reference set. They now recommend the equations developed by the Global Lung Initiative (GLI) for referencing to normal for spirometry, diffusion capacity, and lung volumes. For spirometry the GLI was able to integrate data from countries around the world. This allowed ethnicity to be included in their regression equations and, similar to NHANES III, they found ethnicity improved the precision of their equations. They also published an equation that did not account for country of origin that could be applied to individuals of any race/ethnicity (Quanjer PH, et al. Eur Respir J. 2014;43:505-512). This allowed for applying the GLI equations to external data sets with or without ethnicity included as a co-variate.

Given well-established discrepancies in spirometry, it should come as no surprise that applying the race/ethnicity-neutral GLI equations to non-White populations increases the percentage of patients with pulmonary defects (Moffett AT, et al. Am J Respir Crit Care Med. 2021; A1030). Other data suggest that elimination of race/ethnicity as a co-variate improves the association between percent predicted lung function and important outcomes like mortality (McCormack MC, et al. Am J Respir Crit Care Med. 2022;205:723-724). The first analysis implies that by adjusting for race/ethnicity we may be missing abnormalities, and the second suggests accuracy for outcomes is lost. So case closed, right? Let’s abandon race/ethnicity as a co- variate for our spirometry reference equations.

Perhaps, but a few caveats are in order. It’s important to note that doing so would result in a dramatic increase in abnormal findings in otherwise healthy and asymptomatic non-White individuals. This could negatively affect eligibility for employment and military service (Townsend MC, et al. Am J Respir Crit Care Med. 2022;789-790). We’ve also yet to fully explain the factors driving differences in lung function between races. If socioeconomic factors explained the entirety of the difference, it would be easier to argue for elimination of using race/ethnicity in our equations. Currently, the etiology is thought to be multifactorial and is yet to be fully explained (Braun L, et al. Eur Respir J. 2013;41:1362-1370).

The more we look for institutional racism, the more we will find it. As we realize that attaining health and wellness is more difficult for the disenfranchised, we need to ensure our current practices are part of the solution.

The ERS/ATS guidelines suggest eliminating fixed correction factors for race but do not require elimination of race/ethnicity as a co-variate in the equations selected for use. This seems very reasonable given what we know now. As pulmonary medicine academics and researchers, we need to continue to study the impact integrating race/ethnicity has on precision, accuracy, and clinical outcomes. As pulmonary medicine clinicians, we need to be aware of the reference equations being used in our lab, understand how inclusion of race/ethnicity affects findings, and act accordingly, depending on the clinical situation.
 

Dr. Ghionni is a Pulmonary/Critical Care Fellow, and Dr. Woods is Program Director – PCCM Fellowship and Associate Program Director – IM Residency, Medstar Washington Hospital Center; Dr. Woods is Associate Professor of Medicine, Georgetown University School of Medicine, Washington, DC.

The European Respiratory Society (ERS) and American Thoracic Society (ATS) just published an update to their guidelines on lung function interpretation (Stanojevic S, et al. Eur Respir J. 2022; 60: 2101499). As with any update, the document builds on past work and integrates new advances the field has seen since 2005.

The current iteration comes at a time when academics, clinicians, and epidemiologists are re-analyzing what we think we know about the complex ways race and ethnicity intersect with the practice of medicine. Several experts on lung function testing, many if not most of whom are authors on the ERS/ATS guideline, have written letters or published reviews commenting on the way accounting for race or ethnicity affects lung function interpretation.

Race/ethnicity and lung function was also the topic of an excellent session at the recent CHEST 2022 Annual Meeting in Nashville, Tennessee. Here, we’ll provide a brief review and direct the reader to relevant sources for a more detailed analysis.

Spirometry is an integral part of the diagnosis and management of a wide range of pulmonary conditions. Dr. Aaron Baugh from the University of California San Francisco (UCSF) lectured on the spirometer’s history at CHEST 2022 and detailed its interactions with race over the past 2 centuries. Other authors have chronicled this history, as well (Braun L, et al. Can J Respir Ther. 2015;51[4]:99-101). The short version is that since the British surgeon John Hutchinson created the first spirometer in 1846, race has been a part of the discussion of lung function interpretation.

In 2022, we know far more about the factors that determine lung function than we did in the 19th century. Age, height, and sex assigned at birth all explain a high percentage of the variability seen in FEV1 and FVC. When modeled, race also explains a portion of the variability, and the NHANES III investigators found its inclusion in regression equations, along with age, height, and sex, improved their precision. Case closed, right? Modern medicine is defined by phenotyping, precision, and individualized care, so why shouldn’t race be a part of lung function interpretation?

Well, it’s complicated. With the increasing recognition of health disparities across racial groups the way race is incorporated in medical practice is understandably being scrutinized. As clinicians and academics, we must analyze the root cause of differences in health outcomes between racial groups.

Publications on pulse oximetry (Gottlieb ER, et al. JAMA Intern Med. 2022; 182:849-858) and glomerular filtration rate (Williams WW, et al. N Engl J Med. 2021;385:1804-1806) have revealed some of the ways our use of instruments and equations may exacerbate or perpetuate current disparities. Even small differences in a measure like pulse oximetry could have a profound impact on clinical decisions at the individual and population levels.

The 2022 ERS/ATS lung function interpretation guidelines have abandoned the use of NHANES III as a reference set. They now recommend the equations developed by the Global Lung Initiative (GLI) for referencing to normal for spirometry, diffusion capacity, and lung volumes. For spirometry the GLI was able to integrate data from countries around the world. This allowed ethnicity to be included in their regression equations and, similar to NHANES III, they found ethnicity improved the precision of their equations. They also published an equation that did not account for country of origin that could be applied to individuals of any race/ethnicity (Quanjer PH, et al. Eur Respir J. 2014;43:505-512). This allowed for applying the GLI equations to external data sets with or without ethnicity included as a co-variate.

Given well-established discrepancies in spirometry, it should come as no surprise that applying the race/ethnicity-neutral GLI equations to non-White populations increases the percentage of patients with pulmonary defects (Moffett AT, et al. Am J Respir Crit Care Med. 2021; A1030). Other data suggest that elimination of race/ethnicity as a co-variate improves the association between percent predicted lung function and important outcomes like mortality (McCormack MC, et al. Am J Respir Crit Care Med. 2022;205:723-724). The first analysis implies that by adjusting for race/ethnicity we may be missing abnormalities, and the second suggests accuracy for outcomes is lost. So case closed, right? Let’s abandon race/ethnicity as a co- variate for our spirometry reference equations.

Perhaps, but a few caveats are in order. It’s important to note that doing so would result in a dramatic increase in abnormal findings in otherwise healthy and asymptomatic non-White individuals. This could negatively affect eligibility for employment and military service (Townsend MC, et al. Am J Respir Crit Care Med. 2022;789-790). We’ve also yet to fully explain the factors driving differences in lung function between races. If socioeconomic factors explained the entirety of the difference, it would be easier to argue for elimination of using race/ethnicity in our equations. Currently, the etiology is thought to be multifactorial and is yet to be fully explained (Braun L, et al. Eur Respir J. 2013;41:1362-1370).

The more we look for institutional racism, the more we will find it. As we realize that attaining health and wellness is more difficult for the disenfranchised, we need to ensure our current practices are part of the solution.

The ERS/ATS guidelines suggest eliminating fixed correction factors for race but do not require elimination of race/ethnicity as a co-variate in the equations selected for use. This seems very reasonable given what we know now. As pulmonary medicine academics and researchers, we need to continue to study the impact integrating race/ethnicity has on precision, accuracy, and clinical outcomes. As pulmonary medicine clinicians, we need to be aware of the reference equations being used in our lab, understand how inclusion of race/ethnicity affects findings, and act accordingly, depending on the clinical situation.
 

Dr. Ghionni is a Pulmonary/Critical Care Fellow, and Dr. Woods is Program Director – PCCM Fellowship and Associate Program Director – IM Residency, Medstar Washington Hospital Center; Dr. Woods is Associate Professor of Medicine, Georgetown University School of Medicine, Washington, DC.

The European Respiratory Society (ERS) and American Thoracic Society (ATS) just published an update to their guidelines on lung function interpretation (Stanojevic S, et al. Eur Respir J. 2022; 60: 2101499). As with any update, the document builds on past work and integrates new advances the field has seen since 2005.

The current iteration comes at a time when academics, clinicians, and epidemiologists are re-analyzing what we think we know about the complex ways race and ethnicity intersect with the practice of medicine. Several experts on lung function testing, many if not most of whom are authors on the ERS/ATS guideline, have written letters or published reviews commenting on the way accounting for race or ethnicity affects lung function interpretation.

Race/ethnicity and lung function was also the topic of an excellent session at the recent CHEST 2022 Annual Meeting in Nashville, Tennessee. Here, we’ll provide a brief review and direct the reader to relevant sources for a more detailed analysis.

Spirometry is an integral part of the diagnosis and management of a wide range of pulmonary conditions. Dr. Aaron Baugh from the University of California San Francisco (UCSF) lectured on the spirometer’s history at CHEST 2022 and detailed its interactions with race over the past 2 centuries. Other authors have chronicled this history, as well (Braun L, et al. Can J Respir Ther. 2015;51[4]:99-101). The short version is that since the British surgeon John Hutchinson created the first spirometer in 1846, race has been a part of the discussion of lung function interpretation.

In 2022, we know far more about the factors that determine lung function than we did in the 19th century. Age, height, and sex assigned at birth all explain a high percentage of the variability seen in FEV1 and FVC. When modeled, race also explains a portion of the variability, and the NHANES III investigators found its inclusion in regression equations, along with age, height, and sex, improved their precision. Case closed, right? Modern medicine is defined by phenotyping, precision, and individualized care, so why shouldn’t race be a part of lung function interpretation?

Well, it’s complicated. With the increasing recognition of health disparities across racial groups the way race is incorporated in medical practice is understandably being scrutinized. As clinicians and academics, we must analyze the root cause of differences in health outcomes between racial groups.

Publications on pulse oximetry (Gottlieb ER, et al. JAMA Intern Med. 2022; 182:849-858) and glomerular filtration rate (Williams WW, et al. N Engl J Med. 2021;385:1804-1806) have revealed some of the ways our use of instruments and equations may exacerbate or perpetuate current disparities. Even small differences in a measure like pulse oximetry could have a profound impact on clinical decisions at the individual and population levels.

The 2022 ERS/ATS lung function interpretation guidelines have abandoned the use of NHANES III as a reference set. They now recommend the equations developed by the Global Lung Initiative (GLI) for referencing to normal for spirometry, diffusion capacity, and lung volumes. For spirometry the GLI was able to integrate data from countries around the world. This allowed ethnicity to be included in their regression equations and, similar to NHANES III, they found ethnicity improved the precision of their equations. They also published an equation that did not account for country of origin that could be applied to individuals of any race/ethnicity (Quanjer PH, et al. Eur Respir J. 2014;43:505-512). This allowed for applying the GLI equations to external data sets with or without ethnicity included as a co-variate.

Given well-established discrepancies in spirometry, it should come as no surprise that applying the race/ethnicity-neutral GLI equations to non-White populations increases the percentage of patients with pulmonary defects (Moffett AT, et al. Am J Respir Crit Care Med. 2021; A1030). Other data suggest that elimination of race/ethnicity as a co-variate improves the association between percent predicted lung function and important outcomes like mortality (McCormack MC, et al. Am J Respir Crit Care Med. 2022;205:723-724). The first analysis implies that by adjusting for race/ethnicity we may be missing abnormalities, and the second suggests accuracy for outcomes is lost. So case closed, right? Let’s abandon race/ethnicity as a co- variate for our spirometry reference equations.

Perhaps, but a few caveats are in order. It’s important to note that doing so would result in a dramatic increase in abnormal findings in otherwise healthy and asymptomatic non-White individuals. This could negatively affect eligibility for employment and military service (Townsend MC, et al. Am J Respir Crit Care Med. 2022;789-790). We’ve also yet to fully explain the factors driving differences in lung function between races. If socioeconomic factors explained the entirety of the difference, it would be easier to argue for elimination of using race/ethnicity in our equations. Currently, the etiology is thought to be multifactorial and is yet to be fully explained (Braun L, et al. Eur Respir J. 2013;41:1362-1370).

The more we look for institutional racism, the more we will find it. As we realize that attaining health and wellness is more difficult for the disenfranchised, we need to ensure our current practices are part of the solution.

The ERS/ATS guidelines suggest eliminating fixed correction factors for race but do not require elimination of race/ethnicity as a co-variate in the equations selected for use. This seems very reasonable given what we know now. As pulmonary medicine academics and researchers, we need to continue to study the impact integrating race/ethnicity has on precision, accuracy, and clinical outcomes. As pulmonary medicine clinicians, we need to be aware of the reference equations being used in our lab, understand how inclusion of race/ethnicity affects findings, and act accordingly, depending on the clinical situation.
 

Dr. Ghionni is a Pulmonary/Critical Care Fellow, and Dr. Woods is Program Director – PCCM Fellowship and Associate Program Director – IM Residency, Medstar Washington Hospital Center; Dr. Woods is Associate Professor of Medicine, Georgetown University School of Medicine, Washington, DC.