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Drs. Neil Freedman and Barbara Phillips represented CHEST at an FDA workshop on April 16 on “Study Design Considerations for Devices Including Digital Health Technologies for Sleep-Disordered Breathing (SDB) in Adults. The other organizational participants were The American Academy of Dental Sleep Medicine; The American Academy of Neurology; the American Academy of Otolaryngology, Head and Neck Surgery; The American Academy of Sleep Medicine; and The American Sleep Apnea Association. Here are the questions that the FDA asked the panelists:

1. FDA is seeking to promote innovation and expedite the clinical development of devices intended for the diagnosis and treatment of sleep-disordered breathing (SDB). How should the following conditions (including their severity, eg, mild, moderate, severe, if appropriate) be defined for the purpose of creating appropriate inclusion/exclusion criteria for a clinical study for SDB devices?

a. Apnea

b. Hypopnea

c. Sleep-Disordered Breathing (SDB)

d. Obstructive Sleep Apnea Syndrome (OSAS)

e. Central Sleep Apnea Syndrome (CSAS)

f. Primary Snoring

2. Polysomnography (PSG) has been widely accepted as the “gold standard” test for the diagnosis of OSA and primary snoring. However, home sleep apnea testing (HSAT) has emerged in recent years as an alternative or complementary diagnostic tool for SDB.

a. Can HSAT be used for establishing a baseline diagnosis and for the collection of clinical performance data for device trials for OSA, CSA, or primary snoring? If so, what are the recommended parameters that should be collected by an HSAT (eg, nasal pressure, oximetry, chest and abdominal respiratory inductance plethysmography)?

b. What constitutes a technically adequate test (either PSG or HSAT, if appropriate) for establishing a baseline diagnosis of SDB for device studies (eg, number of hours, number of nights)?

3. FDA has received an increasing number of premarket applications for devices intended to treat SDB. How should studies for the various technologies (eg, intra-oral appliances, externally worn devices, electrosurgical devices for tissue reduction, and passive or active implantable devices of the upper airway) be designed with respect to the following factors (please consider whether your recommendations would vary if the device was an implant vs an externally worn device):

a. What is the most appropriate control group (eg, comparison to baseline measures, randomization to a concurrent control group)?

b. What is the minimum duration of the study? For implants and surgical procedures, how long after the intervention should the effectiveness endpoint be assessed?

c. What objective parameter or combination of parameters should be used for the primary effectiveness endpoints (eg, AHI, ODI, T90, or other non-PSG/HSAT parameters)?

d. What would be a clinically meaningful difference for the above primary effectiveness endpoint(s) between/among study arms or within a study arm?

e. What patient-reported outcomes (PROs) are appropriate in the evaluation of SDB devices?

4. What are the safety and effectiveness concerns when a digital health device provides a diagnosis and monitoring of SDB?

a. What factors are important in developing a reference database (eg, demographics, validation)?b. What are the important safety and effectiveness concerns for SDB digital health devices used in the following settings:

i. A physician office or sleep center environment?

ii. A nonclinical environment?

iii. Prescription vs OTC use?

There was significant discussion and quite a bit of controversy. Among the recommendations to the FDA were that home testing is adequate and acceptable for clinical trials, that the ODI4 is more predictive and reliable than the AHI, and that the syndrome of OSAHS includes symptoms, one of the most important of which is sleepiness. It was acknowledged that digital health devices have the potential to greatly increase access to diagnosis, but access to treatment will need to be addressed, as well. I think this was a very important meeting, and the outcome will likely impact our members. The ultimate goal is to publish a paper about recommended techniques, outcomes, and inclusion characteristics/definitions to be used in clinical trials for new devices to diagnose or treat sleep apnea.

Drs. Neil Freedman and Barbara Phillips represented CHEST at an FDA workshop on April 16 on “Study Design Considerations for Devices Including Digital Health Technologies for Sleep-Disordered Breathing (SDB) in Adults. The other organizational participants were The American Academy of Dental Sleep Medicine; The American Academy of Neurology; the American Academy of Otolaryngology, Head and Neck Surgery; The American Academy of Sleep Medicine; and The American Sleep Apnea Association. Here are the questions that the FDA asked the panelists:

1. FDA is seeking to promote innovation and expedite the clinical development of devices intended for the diagnosis and treatment of sleep-disordered breathing (SDB). How should the following conditions (including their severity, eg, mild, moderate, severe, if appropriate) be defined for the purpose of creating appropriate inclusion/exclusion criteria for a clinical study for SDB devices?

a. Apnea

b. Hypopnea

c. Sleep-Disordered Breathing (SDB)

d. Obstructive Sleep Apnea Syndrome (OSAS)

e. Central Sleep Apnea Syndrome (CSAS)

f. Primary Snoring

2. Polysomnography (PSG) has been widely accepted as the “gold standard” test for the diagnosis of OSA and primary snoring. However, home sleep apnea testing (HSAT) has emerged in recent years as an alternative or complementary diagnostic tool for SDB.

a. Can HSAT be used for establishing a baseline diagnosis and for the collection of clinical performance data for device trials for OSA, CSA, or primary snoring? If so, what are the recommended parameters that should be collected by an HSAT (eg, nasal pressure, oximetry, chest and abdominal respiratory inductance plethysmography)?

b. What constitutes a technically adequate test (either PSG or HSAT, if appropriate) for establishing a baseline diagnosis of SDB for device studies (eg, number of hours, number of nights)?

3. FDA has received an increasing number of premarket applications for devices intended to treat SDB. How should studies for the various technologies (eg, intra-oral appliances, externally worn devices, electrosurgical devices for tissue reduction, and passive or active implantable devices of the upper airway) be designed with respect to the following factors (please consider whether your recommendations would vary if the device was an implant vs an externally worn device):

a. What is the most appropriate control group (eg, comparison to baseline measures, randomization to a concurrent control group)?

b. What is the minimum duration of the study? For implants and surgical procedures, how long after the intervention should the effectiveness endpoint be assessed?

c. What objective parameter or combination of parameters should be used for the primary effectiveness endpoints (eg, AHI, ODI, T90, or other non-PSG/HSAT parameters)?

d. What would be a clinically meaningful difference for the above primary effectiveness endpoint(s) between/among study arms or within a study arm?

e. What patient-reported outcomes (PROs) are appropriate in the evaluation of SDB devices?

4. What are the safety and effectiveness concerns when a digital health device provides a diagnosis and monitoring of SDB?

a. What factors are important in developing a reference database (eg, demographics, validation)?b. What are the important safety and effectiveness concerns for SDB digital health devices used in the following settings:

i. A physician office or sleep center environment?

ii. A nonclinical environment?

iii. Prescription vs OTC use?

There was significant discussion and quite a bit of controversy. Among the recommendations to the FDA were that home testing is adequate and acceptable for clinical trials, that the ODI4 is more predictive and reliable than the AHI, and that the syndrome of OSAHS includes symptoms, one of the most important of which is sleepiness. It was acknowledged that digital health devices have the potential to greatly increase access to diagnosis, but access to treatment will need to be addressed, as well. I think this was a very important meeting, and the outcome will likely impact our members. The ultimate goal is to publish a paper about recommended techniques, outcomes, and inclusion characteristics/definitions to be used in clinical trials for new devices to diagnose or treat sleep apnea.

Drs. Neil Freedman and Barbara Phillips represented CHEST at an FDA workshop on April 16 on “Study Design Considerations for Devices Including Digital Health Technologies for Sleep-Disordered Breathing (SDB) in Adults. The other organizational participants were The American Academy of Dental Sleep Medicine; The American Academy of Neurology; the American Academy of Otolaryngology, Head and Neck Surgery; The American Academy of Sleep Medicine; and The American Sleep Apnea Association. Here are the questions that the FDA asked the panelists:

1. FDA is seeking to promote innovation and expedite the clinical development of devices intended for the diagnosis and treatment of sleep-disordered breathing (SDB). How should the following conditions (including their severity, eg, mild, moderate, severe, if appropriate) be defined for the purpose of creating appropriate inclusion/exclusion criteria for a clinical study for SDB devices?

a. Apnea

b. Hypopnea

c. Sleep-Disordered Breathing (SDB)

d. Obstructive Sleep Apnea Syndrome (OSAS)

e. Central Sleep Apnea Syndrome (CSAS)

f. Primary Snoring

2. Polysomnography (PSG) has been widely accepted as the “gold standard” test for the diagnosis of OSA and primary snoring. However, home sleep apnea testing (HSAT) has emerged in recent years as an alternative or complementary diagnostic tool for SDB.

a. Can HSAT be used for establishing a baseline diagnosis and for the collection of clinical performance data for device trials for OSA, CSA, or primary snoring? If so, what are the recommended parameters that should be collected by an HSAT (eg, nasal pressure, oximetry, chest and abdominal respiratory inductance plethysmography)?

b. What constitutes a technically adequate test (either PSG or HSAT, if appropriate) for establishing a baseline diagnosis of SDB for device studies (eg, number of hours, number of nights)?

3. FDA has received an increasing number of premarket applications for devices intended to treat SDB. How should studies for the various technologies (eg, intra-oral appliances, externally worn devices, electrosurgical devices for tissue reduction, and passive or active implantable devices of the upper airway) be designed with respect to the following factors (please consider whether your recommendations would vary if the device was an implant vs an externally worn device):

a. What is the most appropriate control group (eg, comparison to baseline measures, randomization to a concurrent control group)?

b. What is the minimum duration of the study? For implants and surgical procedures, how long after the intervention should the effectiveness endpoint be assessed?

c. What objective parameter or combination of parameters should be used for the primary effectiveness endpoints (eg, AHI, ODI, T90, or other non-PSG/HSAT parameters)?

d. What would be a clinically meaningful difference for the above primary effectiveness endpoint(s) between/among study arms or within a study arm?

e. What patient-reported outcomes (PROs) are appropriate in the evaluation of SDB devices?

4. What are the safety and effectiveness concerns when a digital health device provides a diagnosis and monitoring of SDB?

a. What factors are important in developing a reference database (eg, demographics, validation)?b. What are the important safety and effectiveness concerns for SDB digital health devices used in the following settings:

i. A physician office or sleep center environment?

ii. A nonclinical environment?

iii. Prescription vs OTC use?

There was significant discussion and quite a bit of controversy. Among the recommendations to the FDA were that home testing is adequate and acceptable for clinical trials, that the ODI4 is more predictive and reliable than the AHI, and that the syndrome of OSAHS includes symptoms, one of the most important of which is sleepiness. It was acknowledged that digital health devices have the potential to greatly increase access to diagnosis, but access to treatment will need to be addressed, as well. I think this was a very important meeting, and the outcome will likely impact our members. The ultimate goal is to publish a paper about recommended techniques, outcomes, and inclusion characteristics/definitions to be used in clinical trials for new devices to diagnose or treat sleep apnea.

Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) each affect at least 10% of the general adult population and, thus, both disorders together, commonly referred to as the overlap syndrome, could be expected in at least 1% of adults by chance alone. However, there is evidence of important interactions between the disorders that influence the prevalence of the overlap, which have implications for the development of comorbidities,and also for management (McNicholas WT. Chest. 2017; 152[6]:1318). Furthermore, sleep quality is typically poor in COPD, which has been linked to worse pulmonary function and lung hyperinflation and may contribute to daytime fatigue.

Interactions between COPD and OSA that may influence the prevalence of overlap

Previous reports have presented conflicting results regarding the likely association between COPD and OSA, which may partly reflect different definitions of OSA, patient populations, and methodologies of investigation. However, COPD represents a spectrum of clinical phenotypes ranging from the hyperinflated patient with low BMI (predominant emphysema phenotype) to the patient with higher BMI and tendency to right-sided heart failure (predominant chronic bronchitis phenotype). The predominant emphysema phenotype may predispose to a lower likelihood of OSA, and there is recent evidence that lung hyperinflation is protective against the development of OSA by lowering the critical closing pressure of the upper airway during sleep. Furthermore, the degree of emphysema and gas trapping on CT scan of the thorax correlates inversely with apnea-hypopnia index in patients with severe COPD (Krachman SL et al. Ann Am Thorac Soc. 2016;13[7]:1129).

In contrast, the predominant chronic bronchitis phenotype predisposes to a higher likelihood of OSA because of higher BMI and likelihood of right-sided heart failure. Peripheral fluid retention in such patients predisposes to OSA because of the rostral fluid shift that occurs during sleep in the supine position, predisposing to upper airway obstruction by airway narrowing. The COPDGene study reports that the chronic bronchitis phenotype has a higher prevalence of OSA even in the absence of differences in BMI and lung function (Kim V et al. Chest. 2011;140[3]:626). Upper airway inflammation associated with cigarette smoking may also contribute to the development of OSA, and corticosteroid therapy may adversely affect upper airway muscle function. OSA also appears to exacerbate lower airway inflammation in COPD. In practice, most patients with COPD have a mixture of emphysema and chronic bronchitis, and the probability of OSA will represent the balance of these protective and promoting factors in individual patients (Fig 1).

While there is evidence of increased mortality in patients with COPD and OSA alone, a recent report based on the Sleep Heart Health Study somewhat surprisingly found that the incremental contribution of declining lung function to mortality diminished with increasing severity of SDB measured by AHI (Putcha N et al. Am J Respir Crit Care Med. 2016;194[8]:1007). Thus, the epidemiologic relationship of COPD and OSA and related clinical outcomes remains an important research topic comparing different clinical phenotypes.
 

Mechanisms of interaction in the overlap syndrome and implications for comorbidity

COPD and OSA are associated with several overlapping physiological and biological disturbances, including hypoxia and inflammation, which may contribute to cardiovascular and other comorbidities. Thus, the probability should be high that the overlap syndrome will be associated with a greater risk of comorbidity than with either disease alone. Patients with the overlap syndrome demonstrate greater degrees of oxygen desaturation predisposing to pulmonary hypertension, which is especially common in these patients.

COPD and OSA are each associated with systemic inflammation and oxidative stress, and C-reactive protein (CRP) has been identified as a measure of systemic inflammation that is commonly elevated in both disorders, although in OSA, concurrent obesity is an important confounding factor. Systemic inflammation contributes to the development of cardiovascular disease, which is a common complication of both COPD and OSA. Thus, one could expect that cardiovascular disease is particularly prevalent in patients with overlap syndrome, but there are limited data on this relationship, which represents an important research topic.
 

Clinical assessment

Patients with the overlap syndrome present with typical clinical features of each disorder and additional features that reflect the higher prevalence of hypoxemia, hypercapnia, and pulmonary hypertension. Thus, morning headaches reflecting hypercapnia and peripheral edema reflecting right-sided heart failure may be especially common. Screening questionnaires may be helpful in the initial evaluation of likely OSA in patients with COPD, and objective clinical data, including anthropometrics such as age, sex, and BMI, and medical history such as cardiovascular comorbidity, are especially useful in clinical prediction (McNicholas WT. Lancet Respir Med. 2016;4[9]:683). Thus, screening for OSA in patients with COPD should not be complicated, and the widespread failure to do so may reflect a lack of awareness of the possible association by the clinician involved.

The specific diagnosis of OSA in COPD requires some form of overnight sleep study, and there is a growing move toward ambulatory studies that focus on cardiorespiratory variables. Overnight monitoring of oxygen saturation is especially useful, particularly if linked to special analysis software, and may be sufficient in many cases. Full polysomnography can be reserved for select cases where the diagnosis remains in doubt.
 

Management and outcomes

Nocturnal hypoxemia in patients with COPD benefits from inhaled, long-acting beta-agonist and anticholinergic therapy, and mean nocturnal oxygen saturation is 2% to 3% higher on each medication compared with placebo. Supplemental oxygen may be indicated when nocturnal oxygen desaturation persists despite optimum pharmacotherapy and does not appear to be associated with significant additional risk of hypercapnia.

However, in patients with COPD-OSA overlap, nonnvasive pressure support is the most appropriate management option. In patients with predominant OSA, continuous positive airway pressure therapy (CPAP) is the preferred option, but where COPD is the dominant component, noninvasive ventilation (NIV) in the form of bi-level positive airway pressure (BIPAP) may be more appropriate. Recent reports in severe COPD indicate that NIV targeted to markedly reduce hypercapnia is associated with improved quality of life and prolonged survival (Köhnlein T et al. Lancet Respir Med. 2014;2[9]:698), and patients with COPD with persistent hypercapnia following hospitalization with an acute exacerbation show improved clinical outcomes and survival with continuing home NIV (Murphy PB et al. JAMA. 2017;317[21]:2177).

The recognition of co-existing OSA in patients with COPD has important clinical relevance as the management of patients with overlap syndrome is different from COPD alone, and the long-term survival of patients with overlap syndrome not treated with nocturnal positive airway pressure is significantly inferior to those patients with overlap syndrome appropriately treated (Marin JM et al. Am J Respir Crit Care Med. 2010;182[3]:325).
 

Dr. McNicholas is with the Department of Respiratory and Sleep Medicine, St. Vincent’s University Hospital, Dublin School of Medicine, University College Dublin, Ireland.

Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) each affect at least 10% of the general adult population and, thus, both disorders together, commonly referred to as the overlap syndrome, could be expected in at least 1% of adults by chance alone. However, there is evidence of important interactions between the disorders that influence the prevalence of the overlap, which have implications for the development of comorbidities,and also for management (McNicholas WT. Chest. 2017; 152[6]:1318). Furthermore, sleep quality is typically poor in COPD, which has been linked to worse pulmonary function and lung hyperinflation and may contribute to daytime fatigue.

Interactions between COPD and OSA that may influence the prevalence of overlap

Previous reports have presented conflicting results regarding the likely association between COPD and OSA, which may partly reflect different definitions of OSA, patient populations, and methodologies of investigation. However, COPD represents a spectrum of clinical phenotypes ranging from the hyperinflated patient with low BMI (predominant emphysema phenotype) to the patient with higher BMI and tendency to right-sided heart failure (predominant chronic bronchitis phenotype). The predominant emphysema phenotype may predispose to a lower likelihood of OSA, and there is recent evidence that lung hyperinflation is protective against the development of OSA by lowering the critical closing pressure of the upper airway during sleep. Furthermore, the degree of emphysema and gas trapping on CT scan of the thorax correlates inversely with apnea-hypopnia index in patients with severe COPD (Krachman SL et al. Ann Am Thorac Soc. 2016;13[7]:1129).

In contrast, the predominant chronic bronchitis phenotype predisposes to a higher likelihood of OSA because of higher BMI and likelihood of right-sided heart failure. Peripheral fluid retention in such patients predisposes to OSA because of the rostral fluid shift that occurs during sleep in the supine position, predisposing to upper airway obstruction by airway narrowing. The COPDGene study reports that the chronic bronchitis phenotype has a higher prevalence of OSA even in the absence of differences in BMI and lung function (Kim V et al. Chest. 2011;140[3]:626). Upper airway inflammation associated with cigarette smoking may also contribute to the development of OSA, and corticosteroid therapy may adversely affect upper airway muscle function. OSA also appears to exacerbate lower airway inflammation in COPD. In practice, most patients with COPD have a mixture of emphysema and chronic bronchitis, and the probability of OSA will represent the balance of these protective and promoting factors in individual patients (Fig 1).

While there is evidence of increased mortality in patients with COPD and OSA alone, a recent report based on the Sleep Heart Health Study somewhat surprisingly found that the incremental contribution of declining lung function to mortality diminished with increasing severity of SDB measured by AHI (Putcha N et al. Am J Respir Crit Care Med. 2016;194[8]:1007). Thus, the epidemiologic relationship of COPD and OSA and related clinical outcomes remains an important research topic comparing different clinical phenotypes.
 

Mechanisms of interaction in the overlap syndrome and implications for comorbidity

COPD and OSA are associated with several overlapping physiological and biological disturbances, including hypoxia and inflammation, which may contribute to cardiovascular and other comorbidities. Thus, the probability should be high that the overlap syndrome will be associated with a greater risk of comorbidity than with either disease alone. Patients with the overlap syndrome demonstrate greater degrees of oxygen desaturation predisposing to pulmonary hypertension, which is especially common in these patients.

COPD and OSA are each associated with systemic inflammation and oxidative stress, and C-reactive protein (CRP) has been identified as a measure of systemic inflammation that is commonly elevated in both disorders, although in OSA, concurrent obesity is an important confounding factor. Systemic inflammation contributes to the development of cardiovascular disease, which is a common complication of both COPD and OSA. Thus, one could expect that cardiovascular disease is particularly prevalent in patients with overlap syndrome, but there are limited data on this relationship, which represents an important research topic.
 

Clinical assessment

Patients with the overlap syndrome present with typical clinical features of each disorder and additional features that reflect the higher prevalence of hypoxemia, hypercapnia, and pulmonary hypertension. Thus, morning headaches reflecting hypercapnia and peripheral edema reflecting right-sided heart failure may be especially common. Screening questionnaires may be helpful in the initial evaluation of likely OSA in patients with COPD, and objective clinical data, including anthropometrics such as age, sex, and BMI, and medical history such as cardiovascular comorbidity, are especially useful in clinical prediction (McNicholas WT. Lancet Respir Med. 2016;4[9]:683). Thus, screening for OSA in patients with COPD should not be complicated, and the widespread failure to do so may reflect a lack of awareness of the possible association by the clinician involved.

The specific diagnosis of OSA in COPD requires some form of overnight sleep study, and there is a growing move toward ambulatory studies that focus on cardiorespiratory variables. Overnight monitoring of oxygen saturation is especially useful, particularly if linked to special analysis software, and may be sufficient in many cases. Full polysomnography can be reserved for select cases where the diagnosis remains in doubt.
 

Management and outcomes

Nocturnal hypoxemia in patients with COPD benefits from inhaled, long-acting beta-agonist and anticholinergic therapy, and mean nocturnal oxygen saturation is 2% to 3% higher on each medication compared with placebo. Supplemental oxygen may be indicated when nocturnal oxygen desaturation persists despite optimum pharmacotherapy and does not appear to be associated with significant additional risk of hypercapnia.

However, in patients with COPD-OSA overlap, nonnvasive pressure support is the most appropriate management option. In patients with predominant OSA, continuous positive airway pressure therapy (CPAP) is the preferred option, but where COPD is the dominant component, noninvasive ventilation (NIV) in the form of bi-level positive airway pressure (BIPAP) may be more appropriate. Recent reports in severe COPD indicate that NIV targeted to markedly reduce hypercapnia is associated with improved quality of life and prolonged survival (Köhnlein T et al. Lancet Respir Med. 2014;2[9]:698), and patients with COPD with persistent hypercapnia following hospitalization with an acute exacerbation show improved clinical outcomes and survival with continuing home NIV (Murphy PB et al. JAMA. 2017;317[21]:2177).

The recognition of co-existing OSA in patients with COPD has important clinical relevance as the management of patients with overlap syndrome is different from COPD alone, and the long-term survival of patients with overlap syndrome not treated with nocturnal positive airway pressure is significantly inferior to those patients with overlap syndrome appropriately treated (Marin JM et al. Am J Respir Crit Care Med. 2010;182[3]:325).
 

Dr. McNicholas is with the Department of Respiratory and Sleep Medicine, St. Vincent’s University Hospital, Dublin School of Medicine, University College Dublin, Ireland.

Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) each affect at least 10% of the general adult population and, thus, both disorders together, commonly referred to as the overlap syndrome, could be expected in at least 1% of adults by chance alone. However, there is evidence of important interactions between the disorders that influence the prevalence of the overlap, which have implications for the development of comorbidities,and also for management (McNicholas WT. Chest. 2017; 152[6]:1318). Furthermore, sleep quality is typically poor in COPD, which has been linked to worse pulmonary function and lung hyperinflation and may contribute to daytime fatigue.

Interactions between COPD and OSA that may influence the prevalence of overlap

Previous reports have presented conflicting results regarding the likely association between COPD and OSA, which may partly reflect different definitions of OSA, patient populations, and methodologies of investigation. However, COPD represents a spectrum of clinical phenotypes ranging from the hyperinflated patient with low BMI (predominant emphysema phenotype) to the patient with higher BMI and tendency to right-sided heart failure (predominant chronic bronchitis phenotype). The predominant emphysema phenotype may predispose to a lower likelihood of OSA, and there is recent evidence that lung hyperinflation is protective against the development of OSA by lowering the critical closing pressure of the upper airway during sleep. Furthermore, the degree of emphysema and gas trapping on CT scan of the thorax correlates inversely with apnea-hypopnia index in patients with severe COPD (Krachman SL et al. Ann Am Thorac Soc. 2016;13[7]:1129).

In contrast, the predominant chronic bronchitis phenotype predisposes to a higher likelihood of OSA because of higher BMI and likelihood of right-sided heart failure. Peripheral fluid retention in such patients predisposes to OSA because of the rostral fluid shift that occurs during sleep in the supine position, predisposing to upper airway obstruction by airway narrowing. The COPDGene study reports that the chronic bronchitis phenotype has a higher prevalence of OSA even in the absence of differences in BMI and lung function (Kim V et al. Chest. 2011;140[3]:626). Upper airway inflammation associated with cigarette smoking may also contribute to the development of OSA, and corticosteroid therapy may adversely affect upper airway muscle function. OSA also appears to exacerbate lower airway inflammation in COPD. In practice, most patients with COPD have a mixture of emphysema and chronic bronchitis, and the probability of OSA will represent the balance of these protective and promoting factors in individual patients (Fig 1).

While there is evidence of increased mortality in patients with COPD and OSA alone, a recent report based on the Sleep Heart Health Study somewhat surprisingly found that the incremental contribution of declining lung function to mortality diminished with increasing severity of SDB measured by AHI (Putcha N et al. Am J Respir Crit Care Med. 2016;194[8]:1007). Thus, the epidemiologic relationship of COPD and OSA and related clinical outcomes remains an important research topic comparing different clinical phenotypes.
 

Mechanisms of interaction in the overlap syndrome and implications for comorbidity

COPD and OSA are associated with several overlapping physiological and biological disturbances, including hypoxia and inflammation, which may contribute to cardiovascular and other comorbidities. Thus, the probability should be high that the overlap syndrome will be associated with a greater risk of comorbidity than with either disease alone. Patients with the overlap syndrome demonstrate greater degrees of oxygen desaturation predisposing to pulmonary hypertension, which is especially common in these patients.

COPD and OSA are each associated with systemic inflammation and oxidative stress, and C-reactive protein (CRP) has been identified as a measure of systemic inflammation that is commonly elevated in both disorders, although in OSA, concurrent obesity is an important confounding factor. Systemic inflammation contributes to the development of cardiovascular disease, which is a common complication of both COPD and OSA. Thus, one could expect that cardiovascular disease is particularly prevalent in patients with overlap syndrome, but there are limited data on this relationship, which represents an important research topic.
 

Clinical assessment

Patients with the overlap syndrome present with typical clinical features of each disorder and additional features that reflect the higher prevalence of hypoxemia, hypercapnia, and pulmonary hypertension. Thus, morning headaches reflecting hypercapnia and peripheral edema reflecting right-sided heart failure may be especially common. Screening questionnaires may be helpful in the initial evaluation of likely OSA in patients with COPD, and objective clinical data, including anthropometrics such as age, sex, and BMI, and medical history such as cardiovascular comorbidity, are especially useful in clinical prediction (McNicholas WT. Lancet Respir Med. 2016;4[9]:683). Thus, screening for OSA in patients with COPD should not be complicated, and the widespread failure to do so may reflect a lack of awareness of the possible association by the clinician involved.

The specific diagnosis of OSA in COPD requires some form of overnight sleep study, and there is a growing move toward ambulatory studies that focus on cardiorespiratory variables. Overnight monitoring of oxygen saturation is especially useful, particularly if linked to special analysis software, and may be sufficient in many cases. Full polysomnography can be reserved for select cases where the diagnosis remains in doubt.
 

Management and outcomes

Nocturnal hypoxemia in patients with COPD benefits from inhaled, long-acting beta-agonist and anticholinergic therapy, and mean nocturnal oxygen saturation is 2% to 3% higher on each medication compared with placebo. Supplemental oxygen may be indicated when nocturnal oxygen desaturation persists despite optimum pharmacotherapy and does not appear to be associated with significant additional risk of hypercapnia.

However, in patients with COPD-OSA overlap, nonnvasive pressure support is the most appropriate management option. In patients with predominant OSA, continuous positive airway pressure therapy (CPAP) is the preferred option, but where COPD is the dominant component, noninvasive ventilation (NIV) in the form of bi-level positive airway pressure (BIPAP) may be more appropriate. Recent reports in severe COPD indicate that NIV targeted to markedly reduce hypercapnia is associated with improved quality of life and prolonged survival (Köhnlein T et al. Lancet Respir Med. 2014;2[9]:698), and patients with COPD with persistent hypercapnia following hospitalization with an acute exacerbation show improved clinical outcomes and survival with continuing home NIV (Murphy PB et al. JAMA. 2017;317[21]:2177).

The recognition of co-existing OSA in patients with COPD has important clinical relevance as the management of patients with overlap syndrome is different from COPD alone, and the long-term survival of patients with overlap syndrome not treated with nocturnal positive airway pressure is significantly inferior to those patients with overlap syndrome appropriately treated (Marin JM et al. Am J Respir Crit Care Med. 2010;182[3]:325).
 

Dr. McNicholas is with the Department of Respiratory and Sleep Medicine, St. Vincent’s University Hospital, Dublin School of Medicine, University College Dublin, Ireland.

One of the best ways to stay connected with CHEST and up-to-date on the latest news and research is through our social channels. Twitter is a social platform that is constantly growing for the organization. Since 2009, we’ve had the opportunity to connect with over 20,000 individuals and impact millions with just a simple tweet or sharing of information. As a means to inform our highly active audience and bring the conversation to a social space, we’ve utilized the platform to help drive the conversation on various topics. CHEST moderates a public conversation via Twitter (@accpchest) around topics in pulmonary, critical care, and sleep medicine every few weeks.

So, what exactly is a Twitter chat? Twitter chats are conversations that are held on the social platform and linked together by a distinct hashtag. We typically use the hashtag #pulmCC (which stands for pulmonary, critical care) and allow individuals from all across the globe to join in on the conversation and share their input. In addition to being a great networking opportunity, our chat recently began offering MOC points to CHEST members who attend Twitter chats and are eligible to receive participation points. We recently began offering CME credit for some of our chats, as well.

Over the last 6 years, we’ve hosted a wide range of Twitter chat topics, ranging from asthma to lung cancer. Some of those chats focused on the following topics:

• The Best of 2017: Highlights, Advancements, New Science
• Improving Lung Health Through Pulmonary Rehabilitation
• Caring for the Caregiver: Vulnerability and Burnout
• What Trainees Need to Know About Pulmonary, Critical Care & Sleep
• #VTEonSoMe Twitter Chat—Let’s Talk Blood Clots! Surgeries, Birth Control, and 40

This past March, we held our Twitter chat Sepsis: Revisions, Advancements, New Therapies, led by Drs. Chris Carroll, Alex Niven, and Steven Q. Simpson. We had over 4.2 million impressions!

Every Twitter chat serves a different purpose, typically based on the topic and the individuals we believe would be most interested in the topic. These chats help us spark conversations on the latest research, advancements, and potential opportunities within the pulmonary/critical care field. They also provide physicians with a great opportunity to network and get acquainted with the #pulmCC community.

One of the best ways to stay connected with CHEST and up-to-date on the latest news and research is through our social channels. Twitter is a social platform that is constantly growing for the organization. Since 2009, we’ve had the opportunity to connect with over 20,000 individuals and impact millions with just a simple tweet or sharing of information. As a means to inform our highly active audience and bring the conversation to a social space, we’ve utilized the platform to help drive the conversation on various topics. CHEST moderates a public conversation via Twitter (@accpchest) around topics in pulmonary, critical care, and sleep medicine every few weeks.

So, what exactly is a Twitter chat? Twitter chats are conversations that are held on the social platform and linked together by a distinct hashtag. We typically use the hashtag #pulmCC (which stands for pulmonary, critical care) and allow individuals from all across the globe to join in on the conversation and share their input. In addition to being a great networking opportunity, our chat recently began offering MOC points to CHEST members who attend Twitter chats and are eligible to receive participation points. We recently began offering CME credit for some of our chats, as well.

Over the last 6 years, we’ve hosted a wide range of Twitter chat topics, ranging from asthma to lung cancer. Some of those chats focused on the following topics:

• The Best of 2017: Highlights, Advancements, New Science
• Improving Lung Health Through Pulmonary Rehabilitation
• Caring for the Caregiver: Vulnerability and Burnout
• What Trainees Need to Know About Pulmonary, Critical Care & Sleep
• #VTEonSoMe Twitter Chat—Let’s Talk Blood Clots! Surgeries, Birth Control, and 40

This past March, we held our Twitter chat Sepsis: Revisions, Advancements, New Therapies, led by Drs. Chris Carroll, Alex Niven, and Steven Q. Simpson. We had over 4.2 million impressions!

Every Twitter chat serves a different purpose, typically based on the topic and the individuals we believe would be most interested in the topic. These chats help us spark conversations on the latest research, advancements, and potential opportunities within the pulmonary/critical care field. They also provide physicians with a great opportunity to network and get acquainted with the #pulmCC community.

One of the best ways to stay connected with CHEST and up-to-date on the latest news and research is through our social channels. Twitter is a social platform that is constantly growing for the organization. Since 2009, we’ve had the opportunity to connect with over 20,000 individuals and impact millions with just a simple tweet or sharing of information. As a means to inform our highly active audience and bring the conversation to a social space, we’ve utilized the platform to help drive the conversation on various topics. CHEST moderates a public conversation via Twitter (@accpchest) around topics in pulmonary, critical care, and sleep medicine every few weeks.

So, what exactly is a Twitter chat? Twitter chats are conversations that are held on the social platform and linked together by a distinct hashtag. We typically use the hashtag #pulmCC (which stands for pulmonary, critical care) and allow individuals from all across the globe to join in on the conversation and share their input. In addition to being a great networking opportunity, our chat recently began offering MOC points to CHEST members who attend Twitter chats and are eligible to receive participation points. We recently began offering CME credit for some of our chats, as well.

Over the last 6 years, we’ve hosted a wide range of Twitter chat topics, ranging from asthma to lung cancer. Some of those chats focused on the following topics:

• The Best of 2017: Highlights, Advancements, New Science
• Improving Lung Health Through Pulmonary Rehabilitation
• Caring for the Caregiver: Vulnerability and Burnout
• What Trainees Need to Know About Pulmonary, Critical Care & Sleep
• #VTEonSoMe Twitter Chat—Let’s Talk Blood Clots! Surgeries, Birth Control, and 40

This past March, we held our Twitter chat Sepsis: Revisions, Advancements, New Therapies, led by Drs. Chris Carroll, Alex Niven, and Steven Q. Simpson. We had over 4.2 million impressions!

Every Twitter chat serves a different purpose, typically based on the topic and the individuals we believe would be most interested in the topic. These chats help us spark conversations on the latest research, advancements, and potential opportunities within the pulmonary/critical care field. They also provide physicians with a great opportunity to network and get acquainted with the #pulmCC community.

Giants In Chest Medicine

Sonia Buist, MBChB. By Dr. J.A. Krishnan.
 

Editorial

Is Big Tobacco Still Trying to Deceive the Public? This Is No Time to Rest on Our Laurels. By Drs. D. R. McCaffree and N. R. Desai.
 

Original Research

Defining the “Frequent Exacerbator” Phenotype in COPD: A Hypothesis-Free Approach. By Dr. O. Le Rouzic, et al.



Trial Duration and Risk Reduction in Combination Therapy Trials for Pulmonary Arterial Hypertension: A Systematic Review. By Dr. A. C. Lajoie, et al.



Tai Chi and Pulmonary Rehabilitation Compared for Treatment-Naive Patients With COPD: A Randomized Controlled Trial. By Dr. M. I. Polkey, et al.

Giants In Chest Medicine

Sonia Buist, MBChB. By Dr. J.A. Krishnan.
 

Editorial

Is Big Tobacco Still Trying to Deceive the Public? This Is No Time to Rest on Our Laurels. By Drs. D. R. McCaffree and N. R. Desai.
 

Original Research

Defining the “Frequent Exacerbator” Phenotype in COPD: A Hypothesis-Free Approach. By Dr. O. Le Rouzic, et al.



Trial Duration and Risk Reduction in Combination Therapy Trials for Pulmonary Arterial Hypertension: A Systematic Review. By Dr. A. C. Lajoie, et al.



Tai Chi and Pulmonary Rehabilitation Compared for Treatment-Naive Patients With COPD: A Randomized Controlled Trial. By Dr. M. I. Polkey, et al.

Giants In Chest Medicine

Sonia Buist, MBChB. By Dr. J.A. Krishnan.
 

Editorial

Is Big Tobacco Still Trying to Deceive the Public? This Is No Time to Rest on Our Laurels. By Drs. D. R. McCaffree and N. R. Desai.
 

Original Research

Defining the “Frequent Exacerbator” Phenotype in COPD: A Hypothesis-Free Approach. By Dr. O. Le Rouzic, et al.



Trial Duration and Risk Reduction in Combination Therapy Trials for Pulmonary Arterial Hypertension: A Systematic Review. By Dr. A. C. Lajoie, et al.



Tai Chi and Pulmonary Rehabilitation Compared for Treatment-Naive Patients With COPD: A Randomized Controlled Trial. By Dr. M. I. Polkey, et al.

Interventional Chest/Diagnostic Procedures

Review of The AMPLE Trial: is talc making a comeback?

A proposed advantage of indwelling pleural catheters (IPC) is their purported ability to reduce hospitalization time when compared with the more traditional talc pleurodesis procedure. The recently published AMPLE trial was a multicenter randomized trial comparing the impact of IPCs vs talc pleurodesis on hospitalization days in patients with malignant pleural effusions. One-hundred forty-six patients were randomized for pleurodesis to either IPC vs pleurodesis via talc slurry in nine centers in Australia, New Zealand, Singapore, and Hong Kong. Patients were followed for up to 12 months. Secondary outcomes included need for further pleural intervention, breathlessness, quality of life, and adverse events.

Patients randomized to IPC spent on average 2 days less in the hospital (10 vs 12 days), a difference that was statistically significant, though of questionable clinical relevance, and somewhat disappointing in light of a prior prospective study from the same group suggesting a benefit of 6 to 7 days (Fysh. Chest. 2012;142[2]:394. As in previous studies, additional pleural procedures were more common in the talc group, adverse events occurred more frequently with IPC, but breathlessness and quality of life were identical in both groups.

This study raises interesting questions. Clearly, IPCs have been favored over talc pleurodesis in the US in the last decade, primarily because of a perceived benefit in terms of hospitalization time. In the absence of clear advantage of IPC on time spent in the hospital, impact on breathlessness and quality of life, and considering the inconvenience of frequent drainage, co-pay incurred by patients, and increased adverse events with IPC, the pendulum may swing again toward talc pleurodesis.

Christine Argento, MD, FCCP

Fabien Maldonado, MD, FCCP

Steering Committee Members

Pediatric Chest Medicine

Early escalation of inhaled corticosteroids: does it help prevent asthma exacerbations?

Asthma is one of the most common chronic conditions in children. The importance of effective control of asthma to prevent exacerbations is well accepted. Inhaled corticosteroids (ICS) are a preferred component of treatment to improve asthma control in children with persistent asthma; however, exacerbations can still occur and result in significant morbidity. Most patients receive systemic corticosteroids during acute asthma exacerbations. The most recent Global Initiative for Asthma (GINA) guidelines recommend increasing ICS at the first signs of an asthma exacerbation in an effort to lessen the need for systemic corticosteroids (GINA. Global strategy for asthma management and prevention. 2017. http://www.ginasthma.org/).

In a recent issue of the New England Journal of Medicine, Jackson and colleagues at the National Heart, Lung, and Blood Institute AsthmaNet published the results of a randomized, double-blind 48-week trial, which included 254 children between ages 5 and 11 years with mild-moderate asthma. Their objectives were to compare exacerbation rates, time to first exacerbation, acute care visits, and bronchodilator use in children randomized to treatment with either high (5 x baseline ICS dose x 7 days) or low dose inhaled corticosteroids early in a drop to the “yellow zone” (Jackson, et al. N Engl J Med. 2018;378[10]:891).

Time to asthma exacerbations and exacerbations that required treatment with corticosteroids did not significantly differ between the low dose and high dose groups. Unexpectedly, the rate of exacerbations was higher with the high dose compared with the low dose group (0.48 vs 0.37). The children who were in the high dose group received 16% more ICS compared with the low dose group. Although not significant, there was a lower linear growth rate, ~0.23 cm per year seen in this high-dose group than in the low-dose group. Additionally, the use of bronchodilator, symptoms, and the rates of evaluation by a physician (ie, emergency department or urgent care visits) did not significantly differ between the two groups.

This study was specific to school-age children with mild-moderate persistent asthma treated with low dose ICS with a history of good adherence. Overall, this well-designed study helps address a question that many clinicians have regarding escalating ICS in the “yellow zone.” Escalating ICS did not reduce exacerbations at the cost of a lower linear growth rate. When it comes to escalating ICS for asthma exacerbation, more is not better.

In conclusion, in children with mild-to-moderate persistent asthma treated with daily inhaled glucocorticoids, quintupling the dose at the early signs of loss of asthma control did not reduce the rate of severe asthma exacerbations or improve other asthma outcomes and may be associated with diminished linear growth. (Funded by the National Heart, Lung, and Blood Institute; STICS ClinicalTrials.gov number, NCT02066129).

John Bishara, DO

Fellow-in-Training Member

Pulmonary Physiology, Function, and Rehabilitation

Understanding cardiopulmonary exercise testing

The cardiopulmonary exercise test (CPET) is an underutilized tool for evaluating patients with dyspnea of uncertain etiology. This is often due to the daunting task of trying to make sense of seemingly large amounts of interacting data, along with clinicians not having been taught a systematic approach for interpreting the results. Unlike other typical tests we order that point to a specific laboratory or anatomic radiographic abnormality, narrowing our differential to a few possibilities, one needs a different mindset when interpreting a CPET. This is a study to demonstrate the body’s normal or abnormal physiologic responses to increasing levels of physical stress. Because different conditions can give similar findings, the physiologic abnormalities must be interpreted in the context of the clinical presentation. If the results do not entirely fit the suspected diagnosis, they should be reported in a manner that may help guide the ordering physician down an alternate pathway. This CHEST NetWork has sought ways to reach out to members to promote a better understanding of the utilization of the basics of pulmonary physiology in the management of patients. We created an online two-part video demonstrating a basic systematic approach toward understanding the combinations of findings one often sees when performing a CPET. A comprehensive understanding cannot be shown in a 40-minute video series, but, hopefully, this will give a starting point to make this task easier and more enjoyable.

Zachary Morris, MD, FCCP

Steering Committee Member

Pulmonary Vascular Disease

BMPR2 mutation regulates singular millimetric fibrovascular lesions in bronchial circulation in PAH

Patients with PAH with BMPR2 mutation are younger with worse hemodynamics, ie, higher mean PAP with higher PVR and a lower cardiac index in comparison to the noncarriers. A systematic analysis of pulmonary imaging using CT angiography or magnetic resonance imaging in patients with PAH demonstrated increased bronchial arterial hypertrophy in BMPR2 mutation carriers compared with those without the mutation. Moreover, hemoptysis is more frequently encountered in patients with PAH with BMPR2 mutation and presumably related to bronchial artery remodeling and angiogenesis. French investigators described, in histopathology findings of explanted lungs of 44 patients with PAH (23 carriers of BMPR2 and 21 noncarriers), unusual singular millimetric fibrovascular lesions (SiMFi) in patients with BMPR2 mutations. The SiMFi is a structure of millimetric dimension with fibrovascular characteristics that are extremely rich in collagen and displayed more than one vascular channel. SiMFi did not show a classic glomeruloid pattern with predominant endothelial cell proliferation as seen in plexiform lesions but rather a large conglomerate of hypertrophic vessels. Performing an ink injection experiment in a freshly explanted lung highlighted a patent connection between bronchial/systemic vessels and pulmonary septal veins. SiMFis had an increased amount of bronchial microvessels and showed increased hypertrophy of larger bronchial arteries. SiMFi is directly related to hypertrophy and/or angiogenesis of vasa vasorum/bronchial arteries in the vicinity of the diseased artery. In patients with PAH with BMPR2 mutations, bronchial angiogenesis is more prevalent compared with patients with PAH lacking these mutations. This highlights the role of bronchial arteries in the spectrum of PAH.

Hector Cajigas, MD, FCCP

Sandeep Sahay, MD, FCCP

Steering Committee Members

References

1.Ghigna MR, et al. BMPR2 mutation status influences bronchial vascular changes in pulmonary arterial hypertension. Eur Respir J. 2016;48[6]:1668. Epub 2016 Nov 3.

2. Tio D, et al. Risk factors for hemoptysis in idiopathic and hereditary pulmonary arterial hypertension. PLoS One. 2013;8:e78132.

3. Elliott CG, et al. Relationship of BMPR2 mutations to vasoreactivity in pulmonary arterial hypertension. Circulation. 2006;113[21]:2509.

Thoracic Oncology

We have a lung cancer screening test but we could use it better

The American Lung Association recently demonstrated the majority of current and former smokers don’t know about lung cancer screening (LCS) with low-dose CT scanning.¹ Researchers estimate less than 5% of eligible persons received LCS.² Awareness campaigns targeting patients and health care providers at the local level can improve LCS uptake.^3,4 While any new clinical practice has an expected implementation delay, LCS has another implementation barrier: complex eligibility criteria (age 55 – 80 years PLUS 30+ pack-year smoking history PLUS quit time less than 15 years). Electronic health record (EHR) tools might accelerate the adoption curve to identify eligible persons.⁵ Moreover, assessing and recording a qualitative smoking history is challenging, at best. One center showed 96.2% discordance between EHR smoking history and that obtained during shared decision-making visit for LCS.⁶ Mostly, the EHR underreported quantitative pack-year history; meaning LCS-eligible patients might fail to be identified by EHR review alone. Another small pilot showed that some patients age 55 – 79 years will update their EHR smoking history using patient portal, but this will not be effective for all patients.⁷ For current smokers, age alone may be an effective identification strategy, given the average start time for most smokers.⁸

Even though current LCS guidelines leave out some individuals at high risk for lung cancer, we must continue efforts to offer this potentially life-saving service to patients now eligible. Using EHR tools may help proactively identify those who are eligible for lung cancer screening.

A bbie Begnaud, MD

NetWork Member

References

1. New Study from American Lung Association’s LUNG FORCE Reveals Low Awareness of Lifesaving Lung Cancer Screening Among Those at Greatest Risk. (2017). http://www.lung.org/about-us/media/press-releases/new-study-lung-cancer-screening.html. Accessed April 19, 2018.

2. Soneji S, et al. Underuse of Chest Radiography Versus Computed Tomography for Lung Cancer Screening. Am J Public Health. 2017;107(8):1248.

3. Cardarelli R, et al. Terminate lung cancer (TLC) study-A mixed-methods population approach to increase lung cancer screening awareness and low-dose computed tomography in Eastern Kentucky. Cancer Epidemiol. 2017;46:1.

4. Jessup, DL, et al. Implementation of digital awareness strategies to engage patients and providers in a lung cancer screening program: retrospective study. J Med Internet Res. 2018;20(2):e52.

5. Comparison of the Electronic Medical Record versus a Shared Decision Making Conversation. Ann Am Thorac Soc. 2018. In press.

6. Modin HE, et al. Pack-year cigarette smoking history for determination of lung cancer screening eligibility. Ann Am Thorac Soc. 2017 Aug;14(8):1320-1325.

7. Begnaud AL, et al. Randomized electronic promotion of lung cancer screening: a pilot. JCO Clinical Cancer Informatics(1), 1-6. doi:10.1200/cci.17.00033

8. The Health Consequences of Smoking—50 Years of Progress: A Report of the Surgeon General. (2014). Atlanta, GA.

Interventional Chest/Diagnostic Procedures

Review of The AMPLE Trial: is talc making a comeback?

A proposed advantage of indwelling pleural catheters (IPC) is their purported ability to reduce hospitalization time when compared with the more traditional talc pleurodesis procedure. The recently published AMPLE trial was a multicenter randomized trial comparing the impact of IPCs vs talc pleurodesis on hospitalization days in patients with malignant pleural effusions. One-hundred forty-six patients were randomized for pleurodesis to either IPC vs pleurodesis via talc slurry in nine centers in Australia, New Zealand, Singapore, and Hong Kong. Patients were followed for up to 12 months. Secondary outcomes included need for further pleural intervention, breathlessness, quality of life, and adverse events.

Patients randomized to IPC spent on average 2 days less in the hospital (10 vs 12 days), a difference that was statistically significant, though of questionable clinical relevance, and somewhat disappointing in light of a prior prospective study from the same group suggesting a benefit of 6 to 7 days (Fysh. Chest. 2012;142[2]:394. As in previous studies, additional pleural procedures were more common in the talc group, adverse events occurred more frequently with IPC, but breathlessness and quality of life were identical in both groups.

This study raises interesting questions. Clearly, IPCs have been favored over talc pleurodesis in the US in the last decade, primarily because of a perceived benefit in terms of hospitalization time. In the absence of clear advantage of IPC on time spent in the hospital, impact on breathlessness and quality of life, and considering the inconvenience of frequent drainage, co-pay incurred by patients, and increased adverse events with IPC, the pendulum may swing again toward talc pleurodesis.

Christine Argento, MD, FCCP

Fabien Maldonado, MD, FCCP

Steering Committee Members

Pediatric Chest Medicine

Early escalation of inhaled corticosteroids: does it help prevent asthma exacerbations?

Asthma is one of the most common chronic conditions in children. The importance of effective control of asthma to prevent exacerbations is well accepted. Inhaled corticosteroids (ICS) are a preferred component of treatment to improve asthma control in children with persistent asthma; however, exacerbations can still occur and result in significant morbidity. Most patients receive systemic corticosteroids during acute asthma exacerbations. The most recent Global Initiative for Asthma (GINA) guidelines recommend increasing ICS at the first signs of an asthma exacerbation in an effort to lessen the need for systemic corticosteroids (GINA. Global strategy for asthma management and prevention. 2017. http://www.ginasthma.org/).

In a recent issue of the New England Journal of Medicine, Jackson and colleagues at the National Heart, Lung, and Blood Institute AsthmaNet published the results of a randomized, double-blind 48-week trial, which included 254 children between ages 5 and 11 years with mild-moderate asthma. Their objectives were to compare exacerbation rates, time to first exacerbation, acute care visits, and bronchodilator use in children randomized to treatment with either high (5 x baseline ICS dose x 7 days) or low dose inhaled corticosteroids early in a drop to the “yellow zone” (Jackson, et al. N Engl J Med. 2018;378[10]:891).

Time to asthma exacerbations and exacerbations that required treatment with corticosteroids did not significantly differ between the low dose and high dose groups. Unexpectedly, the rate of exacerbations was higher with the high dose compared with the low dose group (0.48 vs 0.37). The children who were in the high dose group received 16% more ICS compared with the low dose group. Although not significant, there was a lower linear growth rate, ~0.23 cm per year seen in this high-dose group than in the low-dose group. Additionally, the use of bronchodilator, symptoms, and the rates of evaluation by a physician (ie, emergency department or urgent care visits) did not significantly differ between the two groups.

This study was specific to school-age children with mild-moderate persistent asthma treated with low dose ICS with a history of good adherence. Overall, this well-designed study helps address a question that many clinicians have regarding escalating ICS in the “yellow zone.” Escalating ICS did not reduce exacerbations at the cost of a lower linear growth rate. When it comes to escalating ICS for asthma exacerbation, more is not better.

In conclusion, in children with mild-to-moderate persistent asthma treated with daily inhaled glucocorticoids, quintupling the dose at the early signs of loss of asthma control did not reduce the rate of severe asthma exacerbations or improve other asthma outcomes and may be associated with diminished linear growth. (Funded by the National Heart, Lung, and Blood Institute; STICS ClinicalTrials.gov number, NCT02066129).

John Bishara, DO

Fellow-in-Training Member

Pulmonary Physiology, Function, and Rehabilitation

Understanding cardiopulmonary exercise testing

The cardiopulmonary exercise test (CPET) is an underutilized tool for evaluating patients with dyspnea of uncertain etiology. This is often due to the daunting task of trying to make sense of seemingly large amounts of interacting data, along with clinicians not having been taught a systematic approach for interpreting the results. Unlike other typical tests we order that point to a specific laboratory or anatomic radiographic abnormality, narrowing our differential to a few possibilities, one needs a different mindset when interpreting a CPET. This is a study to demonstrate the body’s normal or abnormal physiologic responses to increasing levels of physical stress. Because different conditions can give similar findings, the physiologic abnormalities must be interpreted in the context of the clinical presentation. If the results do not entirely fit the suspected diagnosis, they should be reported in a manner that may help guide the ordering physician down an alternate pathway. This CHEST NetWork has sought ways to reach out to members to promote a better understanding of the utilization of the basics of pulmonary physiology in the management of patients. We created an online two-part video demonstrating a basic systematic approach toward understanding the combinations of findings one often sees when performing a CPET. A comprehensive understanding cannot be shown in a 40-minute video series, but, hopefully, this will give a starting point to make this task easier and more enjoyable.

Zachary Morris, MD, FCCP

Steering Committee Member

Pulmonary Vascular Disease

BMPR2 mutation regulates singular millimetric fibrovascular lesions in bronchial circulation in PAH

Patients with PAH with BMPR2 mutation are younger with worse hemodynamics, ie, higher mean PAP with higher PVR and a lower cardiac index in comparison to the noncarriers. A systematic analysis of pulmonary imaging using CT angiography or magnetic resonance imaging in patients with PAH demonstrated increased bronchial arterial hypertrophy in BMPR2 mutation carriers compared with those without the mutation. Moreover, hemoptysis is more frequently encountered in patients with PAH with BMPR2 mutation and presumably related to bronchial artery remodeling and angiogenesis. French investigators described, in histopathology findings of explanted lungs of 44 patients with PAH (23 carriers of BMPR2 and 21 noncarriers), unusual singular millimetric fibrovascular lesions (SiMFi) in patients with BMPR2 mutations. The SiMFi is a structure of millimetric dimension with fibrovascular characteristics that are extremely rich in collagen and displayed more than one vascular channel. SiMFi did not show a classic glomeruloid pattern with predominant endothelial cell proliferation as seen in plexiform lesions but rather a large conglomerate of hypertrophic vessels. Performing an ink injection experiment in a freshly explanted lung highlighted a patent connection between bronchial/systemic vessels and pulmonary septal veins. SiMFis had an increased amount of bronchial microvessels and showed increased hypertrophy of larger bronchial arteries. SiMFi is directly related to hypertrophy and/or angiogenesis of vasa vasorum/bronchial arteries in the vicinity of the diseased artery. In patients with PAH with BMPR2 mutations, bronchial angiogenesis is more prevalent compared with patients with PAH lacking these mutations. This highlights the role of bronchial arteries in the spectrum of PAH.

Hector Cajigas, MD, FCCP

Sandeep Sahay, MD, FCCP

Steering Committee Members

References

1.Ghigna MR, et al. BMPR2 mutation status influences bronchial vascular changes in pulmonary arterial hypertension. Eur Respir J. 2016;48[6]:1668. Epub 2016 Nov 3.

2. Tio D, et al. Risk factors for hemoptysis in idiopathic and hereditary pulmonary arterial hypertension. PLoS One. 2013;8:e78132.

3. Elliott CG, et al. Relationship of BMPR2 mutations to vasoreactivity in pulmonary arterial hypertension. Circulation. 2006;113[21]:2509.

Thoracic Oncology

We have a lung cancer screening test but we could use it better

The American Lung Association recently demonstrated the majority of current and former smokers don’t know about lung cancer screening (LCS) with low-dose CT scanning.¹ Researchers estimate less than 5% of eligible persons received LCS.² Awareness campaigns targeting patients and health care providers at the local level can improve LCS uptake.^3,4 While any new clinical practice has an expected implementation delay, LCS has another implementation barrier: complex eligibility criteria (age 55 – 80 years PLUS 30+ pack-year smoking history PLUS quit time less than 15 years). Electronic health record (EHR) tools might accelerate the adoption curve to identify eligible persons.⁵ Moreover, assessing and recording a qualitative smoking history is challenging, at best. One center showed 96.2% discordance between EHR smoking history and that obtained during shared decision-making visit for LCS.⁶ Mostly, the EHR underreported quantitative pack-year history; meaning LCS-eligible patients might fail to be identified by EHR review alone. Another small pilot showed that some patients age 55 – 79 years will update their EHR smoking history using patient portal, but this will not be effective for all patients.⁷ For current smokers, age alone may be an effective identification strategy, given the average start time for most smokers.⁸

Even though current LCS guidelines leave out some individuals at high risk for lung cancer, we must continue efforts to offer this potentially life-saving service to patients now eligible. Using EHR tools may help proactively identify those who are eligible for lung cancer screening.

A bbie Begnaud, MD

NetWork Member

References

1. New Study from American Lung Association’s LUNG FORCE Reveals Low Awareness of Lifesaving Lung Cancer Screening Among Those at Greatest Risk. (2017). http://www.lung.org/about-us/media/press-releases/new-study-lung-cancer-screening.html. Accessed April 19, 2018.

2. Soneji S, et al. Underuse of Chest Radiography Versus Computed Tomography for Lung Cancer Screening. Am J Public Health. 2017;107(8):1248.

3. Cardarelli R, et al. Terminate lung cancer (TLC) study-A mixed-methods population approach to increase lung cancer screening awareness and low-dose computed tomography in Eastern Kentucky. Cancer Epidemiol. 2017;46:1.

4. Jessup, DL, et al. Implementation of digital awareness strategies to engage patients and providers in a lung cancer screening program: retrospective study. J Med Internet Res. 2018;20(2):e52.

5. Comparison of the Electronic Medical Record versus a Shared Decision Making Conversation. Ann Am Thorac Soc. 2018. In press.

6. Modin HE, et al. Pack-year cigarette smoking history for determination of lung cancer screening eligibility. Ann Am Thorac Soc. 2017 Aug;14(8):1320-1325.

7. Begnaud AL, et al. Randomized electronic promotion of lung cancer screening: a pilot. JCO Clinical Cancer Informatics(1), 1-6. doi:10.1200/cci.17.00033

8. The Health Consequences of Smoking—50 Years of Progress: A Report of the Surgeon General. (2014). Atlanta, GA.

Interventional Chest/Diagnostic Procedures

Review of The AMPLE Trial: is talc making a comeback?

A proposed advantage of indwelling pleural catheters (IPC) is their purported ability to reduce hospitalization time when compared with the more traditional talc pleurodesis procedure. The recently published AMPLE trial was a multicenter randomized trial comparing the impact of IPCs vs talc pleurodesis on hospitalization days in patients with malignant pleural effusions. One-hundred forty-six patients were randomized for pleurodesis to either IPC vs pleurodesis via talc slurry in nine centers in Australia, New Zealand, Singapore, and Hong Kong. Patients were followed for up to 12 months. Secondary outcomes included need for further pleural intervention, breathlessness, quality of life, and adverse events.

Patients randomized to IPC spent on average 2 days less in the hospital (10 vs 12 days), a difference that was statistically significant, though of questionable clinical relevance, and somewhat disappointing in light of a prior prospective study from the same group suggesting a benefit of 6 to 7 days (Fysh. Chest. 2012;142[2]:394. As in previous studies, additional pleural procedures were more common in the talc group, adverse events occurred more frequently with IPC, but breathlessness and quality of life were identical in both groups.

This study raises interesting questions. Clearly, IPCs have been favored over talc pleurodesis in the US in the last decade, primarily because of a perceived benefit in terms of hospitalization time. In the absence of clear advantage of IPC on time spent in the hospital, impact on breathlessness and quality of life, and considering the inconvenience of frequent drainage, co-pay incurred by patients, and increased adverse events with IPC, the pendulum may swing again toward talc pleurodesis.

Christine Argento, MD, FCCP

Fabien Maldonado, MD, FCCP

Steering Committee Members

Pediatric Chest Medicine

Early escalation of inhaled corticosteroids: does it help prevent asthma exacerbations?

Asthma is one of the most common chronic conditions in children. The importance of effective control of asthma to prevent exacerbations is well accepted. Inhaled corticosteroids (ICS) are a preferred component of treatment to improve asthma control in children with persistent asthma; however, exacerbations can still occur and result in significant morbidity. Most patients receive systemic corticosteroids during acute asthma exacerbations. The most recent Global Initiative for Asthma (GINA) guidelines recommend increasing ICS at the first signs of an asthma exacerbation in an effort to lessen the need for systemic corticosteroids (GINA. Global strategy for asthma management and prevention. 2017. http://www.ginasthma.org/).

In a recent issue of the New England Journal of Medicine, Jackson and colleagues at the National Heart, Lung, and Blood Institute AsthmaNet published the results of a randomized, double-blind 48-week trial, which included 254 children between ages 5 and 11 years with mild-moderate asthma. Their objectives were to compare exacerbation rates, time to first exacerbation, acute care visits, and bronchodilator use in children randomized to treatment with either high (5 x baseline ICS dose x 7 days) or low dose inhaled corticosteroids early in a drop to the “yellow zone” (Jackson, et al. N Engl J Med. 2018;378[10]:891).

Time to asthma exacerbations and exacerbations that required treatment with corticosteroids did not significantly differ between the low dose and high dose groups. Unexpectedly, the rate of exacerbations was higher with the high dose compared with the low dose group (0.48 vs 0.37). The children who were in the high dose group received 16% more ICS compared with the low dose group. Although not significant, there was a lower linear growth rate, ~0.23 cm per year seen in this high-dose group than in the low-dose group. Additionally, the use of bronchodilator, symptoms, and the rates of evaluation by a physician (ie, emergency department or urgent care visits) did not significantly differ between the two groups.

This study was specific to school-age children with mild-moderate persistent asthma treated with low dose ICS with a history of good adherence. Overall, this well-designed study helps address a question that many clinicians have regarding escalating ICS in the “yellow zone.” Escalating ICS did not reduce exacerbations at the cost of a lower linear growth rate. When it comes to escalating ICS for asthma exacerbation, more is not better.

In conclusion, in children with mild-to-moderate persistent asthma treated with daily inhaled glucocorticoids, quintupling the dose at the early signs of loss of asthma control did not reduce the rate of severe asthma exacerbations or improve other asthma outcomes and may be associated with diminished linear growth. (Funded by the National Heart, Lung, and Blood Institute; STICS ClinicalTrials.gov number, NCT02066129).

John Bishara, DO

Fellow-in-Training Member

Pulmonary Physiology, Function, and Rehabilitation

Understanding cardiopulmonary exercise testing

The cardiopulmonary exercise test (CPET) is an underutilized tool for evaluating patients with dyspnea of uncertain etiology. This is often due to the daunting task of trying to make sense of seemingly large amounts of interacting data, along with clinicians not having been taught a systematic approach for interpreting the results. Unlike other typical tests we order that point to a specific laboratory or anatomic radiographic abnormality, narrowing our differential to a few possibilities, one needs a different mindset when interpreting a CPET. This is a study to demonstrate the body’s normal or abnormal physiologic responses to increasing levels of physical stress. Because different conditions can give similar findings, the physiologic abnormalities must be interpreted in the context of the clinical presentation. If the results do not entirely fit the suspected diagnosis, they should be reported in a manner that may help guide the ordering physician down an alternate pathway. This CHEST NetWork has sought ways to reach out to members to promote a better understanding of the utilization of the basics of pulmonary physiology in the management of patients. We created an online two-part video demonstrating a basic systematic approach toward understanding the combinations of findings one often sees when performing a CPET. A comprehensive understanding cannot be shown in a 40-minute video series, but, hopefully, this will give a starting point to make this task easier and more enjoyable.

Zachary Morris, MD, FCCP

Steering Committee Member

Pulmonary Vascular Disease

BMPR2 mutation regulates singular millimetric fibrovascular lesions in bronchial circulation in PAH

Patients with PAH with BMPR2 mutation are younger with worse hemodynamics, ie, higher mean PAP with higher PVR and a lower cardiac index in comparison to the noncarriers. A systematic analysis of pulmonary imaging using CT angiography or magnetic resonance imaging in patients with PAH demonstrated increased bronchial arterial hypertrophy in BMPR2 mutation carriers compared with those without the mutation. Moreover, hemoptysis is more frequently encountered in patients with PAH with BMPR2 mutation and presumably related to bronchial artery remodeling and angiogenesis. French investigators described, in histopathology findings of explanted lungs of 44 patients with PAH (23 carriers of BMPR2 and 21 noncarriers), unusual singular millimetric fibrovascular lesions (SiMFi) in patients with BMPR2 mutations. The SiMFi is a structure of millimetric dimension with fibrovascular characteristics that are extremely rich in collagen and displayed more than one vascular channel. SiMFi did not show a classic glomeruloid pattern with predominant endothelial cell proliferation as seen in plexiform lesions but rather a large conglomerate of hypertrophic vessels. Performing an ink injection experiment in a freshly explanted lung highlighted a patent connection between bronchial/systemic vessels and pulmonary septal veins. SiMFis had an increased amount of bronchial microvessels and showed increased hypertrophy of larger bronchial arteries. SiMFi is directly related to hypertrophy and/or angiogenesis of vasa vasorum/bronchial arteries in the vicinity of the diseased artery. In patients with PAH with BMPR2 mutations, bronchial angiogenesis is more prevalent compared with patients with PAH lacking these mutations. This highlights the role of bronchial arteries in the spectrum of PAH.

Hector Cajigas, MD, FCCP

Sandeep Sahay, MD, FCCP

Steering Committee Members

References

1.Ghigna MR, et al. BMPR2 mutation status influences bronchial vascular changes in pulmonary arterial hypertension. Eur Respir J. 2016;48[6]:1668. Epub 2016 Nov 3.

2. Tio D, et al. Risk factors for hemoptysis in idiopathic and hereditary pulmonary arterial hypertension. PLoS One. 2013;8:e78132.

3. Elliott CG, et al. Relationship of BMPR2 mutations to vasoreactivity in pulmonary arterial hypertension. Circulation. 2006;113[21]:2509.

Thoracic Oncology

We have a lung cancer screening test but we could use it better

The American Lung Association recently demonstrated the majority of current and former smokers don’t know about lung cancer screening (LCS) with low-dose CT scanning.¹ Researchers estimate less than 5% of eligible persons received LCS.² Awareness campaigns targeting patients and health care providers at the local level can improve LCS uptake.^3,4 While any new clinical practice has an expected implementation delay, LCS has another implementation barrier: complex eligibility criteria (age 55 – 80 years PLUS 30+ pack-year smoking history PLUS quit time less than 15 years). Electronic health record (EHR) tools might accelerate the adoption curve to identify eligible persons.⁵ Moreover, assessing and recording a qualitative smoking history is challenging, at best. One center showed 96.2% discordance between EHR smoking history and that obtained during shared decision-making visit for LCS.⁶ Mostly, the EHR underreported quantitative pack-year history; meaning LCS-eligible patients might fail to be identified by EHR review alone. Another small pilot showed that some patients age 55 – 79 years will update their EHR smoking history using patient portal, but this will not be effective for all patients.⁷ For current smokers, age alone may be an effective identification strategy, given the average start time for most smokers.⁸

Even though current LCS guidelines leave out some individuals at high risk for lung cancer, we must continue efforts to offer this potentially life-saving service to patients now eligible. Using EHR tools may help proactively identify those who are eligible for lung cancer screening.

A bbie Begnaud, MD

NetWork Member

References

1. New Study from American Lung Association’s LUNG FORCE Reveals Low Awareness of Lifesaving Lung Cancer Screening Among Those at Greatest Risk. (2017). http://www.lung.org/about-us/media/press-releases/new-study-lung-cancer-screening.html. Accessed April 19, 2018.

2. Soneji S, et al. Underuse of Chest Radiography Versus Computed Tomography for Lung Cancer Screening. Am J Public Health. 2017;107(8):1248.

3. Cardarelli R, et al. Terminate lung cancer (TLC) study-A mixed-methods population approach to increase lung cancer screening awareness and low-dose computed tomography in Eastern Kentucky. Cancer Epidemiol. 2017;46:1.

4. Jessup, DL, et al. Implementation of digital awareness strategies to engage patients and providers in a lung cancer screening program: retrospective study. J Med Internet Res. 2018;20(2):e52.

5. Comparison of the Electronic Medical Record versus a Shared Decision Making Conversation. Ann Am Thorac Soc. 2018. In press.

6. Modin HE, et al. Pack-year cigarette smoking history for determination of lung cancer screening eligibility. Ann Am Thorac Soc. 2017 Aug;14(8):1320-1325.

7. Begnaud AL, et al. Randomized electronic promotion of lung cancer screening: a pilot. JCO Clinical Cancer Informatics(1), 1-6. doi:10.1200/cci.17.00033

8. The Health Consequences of Smoking—50 Years of Progress: A Report of the Surgeon General. (2014). Atlanta, GA.

The gender gap exists for women in pulmonary medicine. According to the Medscape Pulmonologist Compensation Report 2017, women pulmonologists earned 23% less than their male counterparts even though:

• 2% of women pulmonologists work part time vs 8% of men;
• more women (66%) than men (48%) reported seeking promotion. (Grisham, 2017)

If we take a look at a recent report done by Doximity that analyzed responses on more than 65,000 licensed US doctors across the country, the report reveals that the gap between female and male physicians across the nation, women on average make about $91,000 less annually (Doximity, 2018).

Despite ever-growing enrollment rates for women in medical schools, female physicians are often underrepresented in academic and research settings. According to a study published in the Journal of National Medical Association, “between 80 and 90 percent of leadership roles in medicine, like medical school deans, are filled by men.” (Morton & Sonnad, 2007)

These astounding gaps do not stop at the clinician’s door. This gender inequality is evident in the women who are receiving medical treatment, as well. There are two major issues that exist for women seeking treatment:
 

1. Not being taken as seriously as male patients:

• Women are more likely to be prescribed sedatives for their pain, and men are more likely to be prescribed pain medication. (L. Calderone, 1990)
• Women are more likely to be treated less aggressively in their initial encounters with the health-care system until they prove that they are as sick as male patients with similar symptoms. (Hoffmann & Tarzian, 2001)
• Nationwide, men wait an average of 49 minutes before receiving an analgesic for acute abdominal pain. Women wait an average of 65 minutes for the same thing. (Chen, et al., 2008)
• Multiple studies have shown that female patients’ symptoms are less likely to be taken seriously by doctors, and women are more likely to be misdiagnosed, have their symptoms go unrecognized, or be told what they’re experiencing is psychosomatic. (Hoffmann & Tarzian, 2001) (Carnlöf, Iwarzon, Jensen-Urstad, Gadler, & Insulander, 2017)

2. Being diagnosed and treated the same as male patients

• Up until 1993 when the National Institutes of Health Revitalization Act mandated that all women and minorities be included in clinical trials funded by the NIH, the guidelines and diagnosis for treatment have historically been based off the archetypal patient: a 154-pound white male. Because of this, women are often misdiagnosed or receive treatments that are ineffective or potentially harmful to their health. Even still, researchers frequently do not enroll an adequate number of women or fail to analyze or report data separately by sex. (MHC Center, 2014)
• Women and men metabolize drugs differently, yet dosages are rarely broken down by sex. Women also experience different side effects and derive different benefits from the same treatments. (Soldin & Mattison, 2009)
• Female patients have a 1.5 to 1.7 times higher chance of having an adverse drug reaction. (Rademaker, 2001)
• There are many diseases and conditions that are alarmingly more prevalent among women. Nonsmoking women are three times more likely to get lung cancer than nonsmoking men, according to a comprehensive 2014 report by Brigham and Women’s Hospital in Boston, called “Women’s Health Can’t Wait.” (MHC Center, 2014)

“While the number of women participating in lung cancer clinical trials has risen, women—particularly those from racial and ethnic minorities—are still less likely to enroll in these trials than men. Even when studies include women, researchers often fail to analyze data by sex or include hormone status or other gender-specific factors, making it difficult to uncover differences in incidence, prevalence, and survivability between men and women and to replicate the studies.” (MHC Center, 2014)In the pulmonary space, there is growing evidence that a number of pulmonary diseases affect women differently and with a greater degree of severity than men. Respiratory conditions that impact women nearly exclusively include pulmonary hypertension, catamenial diseases, and pregnancy-associated asthma exacerbation. (Pinkerton, et al., 2015) According to the CDC, cancer is the number one cause of death for women ages 35-64, and the number one cancer killer in women is lung cancer. Women have been taught to care and take notice of the symptoms of breast cancer, HPV, ovarian cancer, and other “women’s diseases,” and, yet, more women die every day from lung cancer than from breast, ovarian, and uterine cancers combined.
 

Why CHEST?

Now, why does this matter to us at CHEST? What can we do about it? How do we begin to tackle such a large issue that permeates nearly every facet of society?

CHEST is in a unique position to not only address the professional development needs of our female membership, but with the help and leadership of the CHEST Foundation and a new partnership with HealthyWomen, we are poised to address the gaps in education for our clinicians, patients, and the public.

To address these needs, the Women in Pulmonary program was created. Women in Pulmonary started as a yearly luncheon and has expanded into a yearlong program that will work to fill these gaps by not only elevating the wants and needs of women in pulmonary medicine, but also by bringing awareness to clinicians, patients, and the public on diseases that are not typically considered “women’s issues.”

CHEST and HealthyWomen are working to provide education, in the form of free webinars, multimedia resources, and live events to achieve the following outcomes:

Women in Pulmonary Medicine: CHEST and HealthyWomen aim to create the tools and educational opportunities that will empower our female clinicians to elevate their voices and become advocates for their career advancement, as well as improved diagnosis and treatment of women with pulmonary diseases.

Patients, Caregivers, and the Public: With this initiative, CHEST and HealthyWomen strive to empower women with the knowledge they need to become champions of their lung health. We will provide them with talking points, questions and awareness of symptoms of pulmonary conditions and diseases, such as: lung cancer, ILD/IPF, COPD, pulmonary hypertension, and asthma so that they are better able to go to their doctor appointments ready to advocate for the care they need.

Clinicians: CHEST and HealthyWomen will aim to equip all clinicians, not just women, with exposure and education that address gender differences in treatment and diagnosis of diseases like lung cancer, asthma, COPD, PH, and ILD/IPF.

Women in Pulmonary aims to provide essential education to every clinician treating women, promote awareness among patients and the public on key information to improve conversations with their health-care providers, and create opportunities for women in chest medicine to advance their careers through professional development, engagement, networking, and mentorship connections. This program will be one step in the direction of changing how women are viewed in medicine and how diseases are perceived across genders.
 

Bibliography

Calderone K. The influence of gender on the frequency of pain and sedative medication administered to postoperative patients. Sex Roles. 1990;23(11-12): 713-725.

Carnlöf C, et al. Women with PSVY are often misdiagnosed, referred later than men, and have more symptoms after ablation. Scand Cardiovasc J. 2017; 51(6): 299-307.

Chen EH, et al. Gender disparity in analgesic treatment of emergency departmetn patietns with acute abdominal pain. Acad Emerg Med. 2008;15(5):414-418.

Doximity. 2018 Physician Compensation Report. Doximity.

Grisham S. Medscape Pulmonologist Compensation Report 2017. https://www.medscape.com/slideshow/compensation-2017-pulmonary-medicine-6008586. Accessed Jan 16, 2018.

Hoffmann DE, Tarzian AJ. The girl who cried pain: a bias against women in the treatment of pain. J Law Med Ethics. 2001;29(1):13-27.

MHC Center. Sex-Specific Medical Research: Why Women’s Health Can’t Wait. Brigham and Women’s Hospital, Mary Horrigan Connors Center for Women’s Health & Gender Biology. Brigham and Women’s Hospital;2014.

Morton MJ, Sonnad SS. Women on professional society and journal editorial boards. J National Med Assoc. 2007;99(7):764-771.

Pinkerton K, et al. Women and lung disease. sex differences and global health disparities. Am J Respir Crit Care Med. 2015;192(1):11-16.

Rademaker M. (2001). Do women have more adverse drug reactions? Am J Clin Dermatol. 2001;2(6): 349-351.

Soldin O, Mattison M. Sex differences in pharmacokinetics and pharmacodynamics. Clin Pharmacokinetics. 2009;48(3):143-157.

The gender gap exists for women in pulmonary medicine. According to the Medscape Pulmonologist Compensation Report 2017, women pulmonologists earned 23% less than their male counterparts even though:

• 2% of women pulmonologists work part time vs 8% of men;
• more women (66%) than men (48%) reported seeking promotion. (Grisham, 2017)

If we take a look at a recent report done by Doximity that analyzed responses on more than 65,000 licensed US doctors across the country, the report reveals that the gap between female and male physicians across the nation, women on average make about $91,000 less annually (Doximity, 2018).

Despite ever-growing enrollment rates for women in medical schools, female physicians are often underrepresented in academic and research settings. According to a study published in the Journal of National Medical Association, “between 80 and 90 percent of leadership roles in medicine, like medical school deans, are filled by men.” (Morton & Sonnad, 2007)

These astounding gaps do not stop at the clinician’s door. This gender inequality is evident in the women who are receiving medical treatment, as well. There are two major issues that exist for women seeking treatment:
 

1. Not being taken as seriously as male patients:

• Women are more likely to be prescribed sedatives for their pain, and men are more likely to be prescribed pain medication. (L. Calderone, 1990)
• Women are more likely to be treated less aggressively in their initial encounters with the health-care system until they prove that they are as sick as male patients with similar symptoms. (Hoffmann & Tarzian, 2001)
• Nationwide, men wait an average of 49 minutes before receiving an analgesic for acute abdominal pain. Women wait an average of 65 minutes for the same thing. (Chen, et al., 2008)
• Multiple studies have shown that female patients’ symptoms are less likely to be taken seriously by doctors, and women are more likely to be misdiagnosed, have their symptoms go unrecognized, or be told what they’re experiencing is psychosomatic. (Hoffmann & Tarzian, 2001) (Carnlöf, Iwarzon, Jensen-Urstad, Gadler, & Insulander, 2017)

2. Being diagnosed and treated the same as male patients

• Up until 1993 when the National Institutes of Health Revitalization Act mandated that all women and minorities be included in clinical trials funded by the NIH, the guidelines and diagnosis for treatment have historically been based off the archetypal patient: a 154-pound white male. Because of this, women are often misdiagnosed or receive treatments that are ineffective or potentially harmful to their health. Even still, researchers frequently do not enroll an adequate number of women or fail to analyze or report data separately by sex. (MHC Center, 2014)
• Women and men metabolize drugs differently, yet dosages are rarely broken down by sex. Women also experience different side effects and derive different benefits from the same treatments. (Soldin & Mattison, 2009)
• Female patients have a 1.5 to 1.7 times higher chance of having an adverse drug reaction. (Rademaker, 2001)
• There are many diseases and conditions that are alarmingly more prevalent among women. Nonsmoking women are three times more likely to get lung cancer than nonsmoking men, according to a comprehensive 2014 report by Brigham and Women’s Hospital in Boston, called “Women’s Health Can’t Wait.” (MHC Center, 2014)

“While the number of women participating in lung cancer clinical trials has risen, women—particularly those from racial and ethnic minorities—are still less likely to enroll in these trials than men. Even when studies include women, researchers often fail to analyze data by sex or include hormone status or other gender-specific factors, making it difficult to uncover differences in incidence, prevalence, and survivability between men and women and to replicate the studies.” (MHC Center, 2014)In the pulmonary space, there is growing evidence that a number of pulmonary diseases affect women differently and with a greater degree of severity than men. Respiratory conditions that impact women nearly exclusively include pulmonary hypertension, catamenial diseases, and pregnancy-associated asthma exacerbation. (Pinkerton, et al., 2015) According to the CDC, cancer is the number one cause of death for women ages 35-64, and the number one cancer killer in women is lung cancer. Women have been taught to care and take notice of the symptoms of breast cancer, HPV, ovarian cancer, and other “women’s diseases,” and, yet, more women die every day from lung cancer than from breast, ovarian, and uterine cancers combined.
 

Why CHEST?

Now, why does this matter to us at CHEST? What can we do about it? How do we begin to tackle such a large issue that permeates nearly every facet of society?

CHEST is in a unique position to not only address the professional development needs of our female membership, but with the help and leadership of the CHEST Foundation and a new partnership with HealthyWomen, we are poised to address the gaps in education for our clinicians, patients, and the public.

To address these needs, the Women in Pulmonary program was created. Women in Pulmonary started as a yearly luncheon and has expanded into a yearlong program that will work to fill these gaps by not only elevating the wants and needs of women in pulmonary medicine, but also by bringing awareness to clinicians, patients, and the public on diseases that are not typically considered “women’s issues.”

CHEST and HealthyWomen are working to provide education, in the form of free webinars, multimedia resources, and live events to achieve the following outcomes:

Women in Pulmonary Medicine: CHEST and HealthyWomen aim to create the tools and educational opportunities that will empower our female clinicians to elevate their voices and become advocates for their career advancement, as well as improved diagnosis and treatment of women with pulmonary diseases.

Patients, Caregivers, and the Public: With this initiative, CHEST and HealthyWomen strive to empower women with the knowledge they need to become champions of their lung health. We will provide them with talking points, questions and awareness of symptoms of pulmonary conditions and diseases, such as: lung cancer, ILD/IPF, COPD, pulmonary hypertension, and asthma so that they are better able to go to their doctor appointments ready to advocate for the care they need.

Clinicians: CHEST and HealthyWomen will aim to equip all clinicians, not just women, with exposure and education that address gender differences in treatment and diagnosis of diseases like lung cancer, asthma, COPD, PH, and ILD/IPF.

Women in Pulmonary aims to provide essential education to every clinician treating women, promote awareness among patients and the public on key information to improve conversations with their health-care providers, and create opportunities for women in chest medicine to advance their careers through professional development, engagement, networking, and mentorship connections. This program will be one step in the direction of changing how women are viewed in medicine and how diseases are perceived across genders.
 

Bibliography

Calderone K. The influence of gender on the frequency of pain and sedative medication administered to postoperative patients. Sex Roles. 1990;23(11-12): 713-725.

Carnlöf C, et al. Women with PSVY are often misdiagnosed, referred later than men, and have more symptoms after ablation. Scand Cardiovasc J. 2017; 51(6): 299-307.

Chen EH, et al. Gender disparity in analgesic treatment of emergency departmetn patietns with acute abdominal pain. Acad Emerg Med. 2008;15(5):414-418.

Doximity. 2018 Physician Compensation Report. Doximity.

Grisham S. Medscape Pulmonologist Compensation Report 2017. https://www.medscape.com/slideshow/compensation-2017-pulmonary-medicine-6008586. Accessed Jan 16, 2018.

Hoffmann DE, Tarzian AJ. The girl who cried pain: a bias against women in the treatment of pain. J Law Med Ethics. 2001;29(1):13-27.

MHC Center. Sex-Specific Medical Research: Why Women’s Health Can’t Wait. Brigham and Women’s Hospital, Mary Horrigan Connors Center for Women’s Health & Gender Biology. Brigham and Women’s Hospital;2014.

Morton MJ, Sonnad SS. Women on professional society and journal editorial boards. J National Med Assoc. 2007;99(7):764-771.

Pinkerton K, et al. Women and lung disease. sex differences and global health disparities. Am J Respir Crit Care Med. 2015;192(1):11-16.

Rademaker M. (2001). Do women have more adverse drug reactions? Am J Clin Dermatol. 2001;2(6): 349-351.

Soldin O, Mattison M. Sex differences in pharmacokinetics and pharmacodynamics. Clin Pharmacokinetics. 2009;48(3):143-157.

The gender gap exists for women in pulmonary medicine. According to the Medscape Pulmonologist Compensation Report 2017, women pulmonologists earned 23% less than their male counterparts even though:

• 2% of women pulmonologists work part time vs 8% of men;
• more women (66%) than men (48%) reported seeking promotion. (Grisham, 2017)

If we take a look at a recent report done by Doximity that analyzed responses on more than 65,000 licensed US doctors across the country, the report reveals that the gap between female and male physicians across the nation, women on average make about $91,000 less annually (Doximity, 2018).

Despite ever-growing enrollment rates for women in medical schools, female physicians are often underrepresented in academic and research settings. According to a study published in the Journal of National Medical Association, “between 80 and 90 percent of leadership roles in medicine, like medical school deans, are filled by men.” (Morton & Sonnad, 2007)

These astounding gaps do not stop at the clinician’s door. This gender inequality is evident in the women who are receiving medical treatment, as well. There are two major issues that exist for women seeking treatment:
 

1. Not being taken as seriously as male patients:

• Women are more likely to be prescribed sedatives for their pain, and men are more likely to be prescribed pain medication. (L. Calderone, 1990)
• Women are more likely to be treated less aggressively in their initial encounters with the health-care system until they prove that they are as sick as male patients with similar symptoms. (Hoffmann & Tarzian, 2001)
• Nationwide, men wait an average of 49 minutes before receiving an analgesic for acute abdominal pain. Women wait an average of 65 minutes for the same thing. (Chen, et al., 2008)
• Multiple studies have shown that female patients’ symptoms are less likely to be taken seriously by doctors, and women are more likely to be misdiagnosed, have their symptoms go unrecognized, or be told what they’re experiencing is psychosomatic. (Hoffmann & Tarzian, 2001) (Carnlöf, Iwarzon, Jensen-Urstad, Gadler, & Insulander, 2017)

2. Being diagnosed and treated the same as male patients

• Up until 1993 when the National Institutes of Health Revitalization Act mandated that all women and minorities be included in clinical trials funded by the NIH, the guidelines and diagnosis for treatment have historically been based off the archetypal patient: a 154-pound white male. Because of this, women are often misdiagnosed or receive treatments that are ineffective or potentially harmful to their health. Even still, researchers frequently do not enroll an adequate number of women or fail to analyze or report data separately by sex. (MHC Center, 2014)
• Women and men metabolize drugs differently, yet dosages are rarely broken down by sex. Women also experience different side effects and derive different benefits from the same treatments. (Soldin & Mattison, 2009)
• Female patients have a 1.5 to 1.7 times higher chance of having an adverse drug reaction. (Rademaker, 2001)
• There are many diseases and conditions that are alarmingly more prevalent among women. Nonsmoking women are three times more likely to get lung cancer than nonsmoking men, according to a comprehensive 2014 report by Brigham and Women’s Hospital in Boston, called “Women’s Health Can’t Wait.” (MHC Center, 2014)

“While the number of women participating in lung cancer clinical trials has risen, women—particularly those from racial and ethnic minorities—are still less likely to enroll in these trials than men. Even when studies include women, researchers often fail to analyze data by sex or include hormone status or other gender-specific factors, making it difficult to uncover differences in incidence, prevalence, and survivability between men and women and to replicate the studies.” (MHC Center, 2014)In the pulmonary space, there is growing evidence that a number of pulmonary diseases affect women differently and with a greater degree of severity than men. Respiratory conditions that impact women nearly exclusively include pulmonary hypertension, catamenial diseases, and pregnancy-associated asthma exacerbation. (Pinkerton, et al., 2015) According to the CDC, cancer is the number one cause of death for women ages 35-64, and the number one cancer killer in women is lung cancer. Women have been taught to care and take notice of the symptoms of breast cancer, HPV, ovarian cancer, and other “women’s diseases,” and, yet, more women die every day from lung cancer than from breast, ovarian, and uterine cancers combined.
 

Why CHEST?

Now, why does this matter to us at CHEST? What can we do about it? How do we begin to tackle such a large issue that permeates nearly every facet of society?

CHEST is in a unique position to not only address the professional development needs of our female membership, but with the help and leadership of the CHEST Foundation and a new partnership with HealthyWomen, we are poised to address the gaps in education for our clinicians, patients, and the public.

To address these needs, the Women in Pulmonary program was created. Women in Pulmonary started as a yearly luncheon and has expanded into a yearlong program that will work to fill these gaps by not only elevating the wants and needs of women in pulmonary medicine, but also by bringing awareness to clinicians, patients, and the public on diseases that are not typically considered “women’s issues.”

CHEST and HealthyWomen are working to provide education, in the form of free webinars, multimedia resources, and live events to achieve the following outcomes:

Women in Pulmonary Medicine: CHEST and HealthyWomen aim to create the tools and educational opportunities that will empower our female clinicians to elevate their voices and become advocates for their career advancement, as well as improved diagnosis and treatment of women with pulmonary diseases.

Patients, Caregivers, and the Public: With this initiative, CHEST and HealthyWomen strive to empower women with the knowledge they need to become champions of their lung health. We will provide them with talking points, questions and awareness of symptoms of pulmonary conditions and diseases, such as: lung cancer, ILD/IPF, COPD, pulmonary hypertension, and asthma so that they are better able to go to their doctor appointments ready to advocate for the care they need.

Clinicians: CHEST and HealthyWomen will aim to equip all clinicians, not just women, with exposure and education that address gender differences in treatment and diagnosis of diseases like lung cancer, asthma, COPD, PH, and ILD/IPF.

Women in Pulmonary aims to provide essential education to every clinician treating women, promote awareness among patients and the public on key information to improve conversations with their health-care providers, and create opportunities for women in chest medicine to advance their careers through professional development, engagement, networking, and mentorship connections. This program will be one step in the direction of changing how women are viewed in medicine and how diseases are perceived across genders.
 

Bibliography

Calderone K. The influence of gender on the frequency of pain and sedative medication administered to postoperative patients. Sex Roles. 1990;23(11-12): 713-725.

Carnlöf C, et al. Women with PSVY are often misdiagnosed, referred later than men, and have more symptoms after ablation. Scand Cardiovasc J. 2017; 51(6): 299-307.

Chen EH, et al. Gender disparity in analgesic treatment of emergency departmetn patietns with acute abdominal pain. Acad Emerg Med. 2008;15(5):414-418.

Doximity. 2018 Physician Compensation Report. Doximity.

Grisham S. Medscape Pulmonologist Compensation Report 2017. https://www.medscape.com/slideshow/compensation-2017-pulmonary-medicine-6008586. Accessed Jan 16, 2018.

Hoffmann DE, Tarzian AJ. The girl who cried pain: a bias against women in the treatment of pain. J Law Med Ethics. 2001;29(1):13-27.

MHC Center. Sex-Specific Medical Research: Why Women’s Health Can’t Wait. Brigham and Women’s Hospital, Mary Horrigan Connors Center for Women’s Health & Gender Biology. Brigham and Women’s Hospital;2014.

Morton MJ, Sonnad SS. Women on professional society and journal editorial boards. J National Med Assoc. 2007;99(7):764-771.

Pinkerton K, et al. Women and lung disease. sex differences and global health disparities. Am J Respir Crit Care Med. 2015;192(1):11-16.

Rademaker M. (2001). Do women have more adverse drug reactions? Am J Clin Dermatol. 2001;2(6): 349-351.

Soldin O, Mattison M. Sex differences in pharmacokinetics and pharmacodynamics. Clin Pharmacokinetics. 2009;48(3):143-157.

CHEST has been informed of the following members’ deaths. We extend our sincere condolences to friends and family.

Nagesh V Salian, MD, FCCP (2016)



Ted A Calinog, MD, FCCP (2017)



Azam Ansari, MD

(2017)



Arthur E. Schmidt, MD, FCCP (2017)



W. Gerald Rainer, MD, FCCP (2017)

CHEST has been informed of the following members’ deaths. We extend our sincere condolences to friends and family.

Nagesh V Salian, MD, FCCP (2016)



Ted A Calinog, MD, FCCP (2017)



Azam Ansari, MD

(2017)



Arthur E. Schmidt, MD, FCCP (2017)



W. Gerald Rainer, MD, FCCP (2017)

CHEST has been informed of the following members’ deaths. We extend our sincere condolences to friends and family.

Nagesh V Salian, MD, FCCP (2016)



Ted A Calinog, MD, FCCP (2017)



Azam Ansari, MD

(2017)



Arthur E. Schmidt, MD, FCCP (2017)



W. Gerald Rainer, MD, FCCP (2017)

Looking for a research opportunity? Check our website for current programs in your area. If your institution has an opportunity to promote, let us know at [email protected]

Looking for a research opportunity? Check our website for current programs in your area. If your institution has an opportunity to promote, let us know at [email protected]

Looking for a research opportunity? Check our website for current programs in your area. If your institution has an opportunity to promote, let us know at [email protected]

Speaking of the Vascular Annual Meeting, have you registered yet? You won’t want to miss a minute, with postgraduate courses, workshops, concurrent and breakfast sessions, scientific sessions, opportunities to get tips and tricks and to ask the experts and to meet up with old friends and greet all your colleagues. Book your housing by May 22 for discounted rates and the VAM room blocks. Get a rundown of event at the VAM Planner here. Register here; book your hotel here. And … see you in Boston.

Speaking of the Vascular Annual Meeting, have you registered yet? You won’t want to miss a minute, with postgraduate courses, workshops, concurrent and breakfast sessions, scientific sessions, opportunities to get tips and tricks and to ask the experts and to meet up with old friends and greet all your colleagues. Book your housing by May 22 for discounted rates and the VAM room blocks. Get a rundown of event at the VAM Planner here. Register here; book your hotel here. And … see you in Boston.

Speaking of the Vascular Annual Meeting, have you registered yet? You won’t want to miss a minute, with postgraduate courses, workshops, concurrent and breakfast sessions, scientific sessions, opportunities to get tips and tricks and to ask the experts and to meet up with old friends and greet all your colleagues. Book your housing by May 22 for discounted rates and the VAM room blocks. Get a rundown of event at the VAM Planner here. Register here; book your hotel here. And … see you in Boston.

The SVS is debuting a new “Ask the Expert” series at the Vascular Annual Meeting this year, and we need members’ help to build it. “Expert” will consist of four, one-hour sessions, one daily Wednesday through Friday, with cases submitted by members. Please submit a case study you wish to be considered for discussion with one of our experts -- and we hope you attend if your case is selected. The deadline will be in mid-May. Topics are Coding, Aortic Care for Occlusive Disease, Hemodialysis and PAD. Submit your cases here. Email education@vascularsociety with questions.

The SVS is debuting a new “Ask the Expert” series at the Vascular Annual Meeting this year, and we need members’ help to build it. “Expert” will consist of four, one-hour sessions, one daily Wednesday through Friday, with cases submitted by members. Please submit a case study you wish to be considered for discussion with one of our experts -- and we hope you attend if your case is selected. The deadline will be in mid-May. Topics are Coding, Aortic Care for Occlusive Disease, Hemodialysis and PAD. Submit your cases here. Email education@vascularsociety with questions.

The SVS is debuting a new “Ask the Expert” series at the Vascular Annual Meeting this year, and we need members’ help to build it. “Expert” will consist of four, one-hour sessions, one daily Wednesday through Friday, with cases submitted by members. Please submit a case study you wish to be considered for discussion with one of our experts -- and we hope you attend if your case is selected. The deadline will be in mid-May. Topics are Coding, Aortic Care for Occlusive Disease, Hemodialysis and PAD. Submit your cases here. Email education@vascularsociety with questions.