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Airway disorders network: Asthma and COPD section
Betting on asthma: The over and under of diagnosis
Asthma is one of the major chronic respiratory diseases worldwide (WHO 2020), yet it is a clinical syndrome that lacks a consensus on its definition, is comprised of nonspecific respiratory symptoms, and is without a gold standard diagnostic test or a set guideline on confirmation of bronchial hyperresponsiveness (Sá-Sousa A et al. Clin Transl Allergy. 2014 Aug 4;4:24). In addition, once adequately treated, there is an absence of an algorithm to diagnose disease remission (Aaron SD et al. Am J Respir Crit Care Med. 2018 Oct 15;198[8]:1012-20). It is estimated that 20%-70% of people with asthma worldwide across the spectrum of all ages remain undiagnosed.
Spirometry and bronchoprovocation challenges with fixed cut-off values demonstrate reduced sensitivity with day-to-day, diurnal, and long-term variation in airflow obstruction, inflammation, and bronchial hyperresponsiveness (Wang R et al. Thorax. 2021 Jun;76[6]:624-31). Inflammatory biomarkers like fractional exhaled nitric oxide (FeNO) have higher specificity but are subject to diurnal variation and confounding diagnoses.
Overdiagnosis of asthma can result in lost opportunity to diagnose significant cardiopulmonary diseases, unnecessary escalation of the asthma treatment regimen for poorly controlled respiratory symptoms, potential for medication adverse effects, and, increased cost burden to the patient and to the health care system (Aaron SD et al. JAMA. 2017;317:269-79; Shaw D et al. Prim Care Respir J. 2012;21:283-7). Among the newly physician-diagnosed asthmatics, <50% have spirometry performed within 1 year of diagnosis (Sokol KC et al. Am J Med. 2015 May;128[5]:502-8). Spirometry was further underutilized with limit on aerosol-generating procedures during COVID-19 pandemic (Kankaanranta H et al. J Allergy Clin Immunol Pract. 2021 Dec;9[12]:4252-3); 30%-35% obese and nonobese patients with physician-diagnosed asthma did not have current asthma when objectively assessed for airflow limitation (Aaron SD et al. JAMA. 2017;317:269-79; van Huisstede A, et al. Respir Med. 2013;107:1356-64).
Clinical remission is greater in early-onset asthma as compared with late-onset asthma (De Marco R et al. J Allergy Clin Immunol. 2002;110:228-35). If asthma is well controlled, a stepping down treatment regimen is suggested (Global Initiative for Asthma 2021;Usmani et al. J Allergy Clin Immunol Pract. 2017 Sep-Oct;5[5]:1378-87.e5; Hagan JB et al. Allergy. 2014 Apr;69[4]:510-6), and although a randomized trial is lacking, it may be feasible to “undiagnose” patients who don’t experience clinical worsening, airflow obstruction, or bronchial hyperresponsiveness after being tapered off all asthma medications with a low relapse rate (Aaron SD et al. JAMA. 2017;317:269-79; J Fam Pract. 2018;67(11):704-7).
Asthma over- and underdiagnosis is prevalent and has clinical and global health consequences. New standardized algorithms with improved biomarkers may help alter this oversight.
Richa Nahar, MD
Network Member-at-Large
Allen J. Blaivas, DO, FCCP
Network Steering Committee Chair
Diffuse lung disease and lung transplant network: Interstitial lung disease section
Future therapies for IPF
Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by progressive fibrosis, respiratory failure, and a mortality rate of 80% at 5 years. Only two drugs are currently FDA-approved for IPF treatment.
The antifibrotics pirfenidone and nintedanib reduce the rate of forced vital capacity (FVC) decline and improve progression free survival (King TE et al. N Engl J Med. 2014;370:2083-92; King TE et al. N Engl J Med. 2014;370:2071-82). While considered revolutionary when introduced, these medications neither reverse disease progression nor improve symptoms. More recently, the Galapagos ISABELA Phase III clinical trial of ziritaxestat in IPF was discontinued due to an unfavorable risk-benefit profile. Despite this, several prospects for IPF therapy exist.
Post hoc analysis of the INCREASE Trial demonstrated a positive effect of inhaled treprostinil on FVC in patients with IPF and group 3 pulmonary hypertension (Waxman A et al. N Engl J Med. 2021;384:325-34). Consequently, a phase 3 randomized trial investigating its safety and efficacy in patients with IPF alone is ongoing. Additional targeted therapies for IPF are also emerging. Recombinant human pentraxin-2, an inhibitor of monocyte differentiation into proinflammatory macrophages, and pamrevlumab, a recombinant human monoclonal antibody against connective tissue growth factor, both demonstrated attenuation of FVC decline compared with placebo in phase 2 trials. Both are currently in phase 3 studies (Raghu G et al. JAMA. 2018 Jun 12;319[22]:2299-307; Sgalla G et al. Expert Opin Investig Drugs. 2020 Aug;29[8]:771-7) Lastly, in February the Food and Drug Administration granted breakthrough therapy designation to BI 1015550 for treatment of IPF based on a 12-week phase 2 randomized, double-blind, placebo-controlled trial. (Data will be presented at ATS). BI 1015550 is an oral, phosphodiesterase 4B (PDE4B) inhibitor with both antifibrotic and anti-inflammatory properties. These advances in drug development provide hope for a future where IPF is transformed from a fatal disease to one manageable over many years.
Adrian Shifren, MD
Network Member-at-Large
Gabriel Schroeder, MD
Network Member-at-Large
Sleep medicine network: Home-based mechanical ventilation and neuromuscular section
Role of airway clearance therapies in neuromuscular disease
Individuals with neuromuscular weakness have an impaired ability to cough and clear secretions from the airway, which can result in atelectasis and pneumonia. Proximal airway clearance therapies (ACT), including manual lung volume recruitment (LVR) and mechanical in-exsufflation (MI-E), mobilize secretions, improve cough efficacy, maintain chest wall compliance, and slow progression of restrictive lung impairment (Chatwin et al. Respir Med. 2018;136:98-110; Sheers et al. Respirology. 2019;24:512-520).
ACT are recommended in international care guidelines for respiratory management of individuals with neuromuscular disease. At a recent Home-based Mechanical Ventilation and Neuromuscular Disease Section “PEEPS Talking PAP” rounds, participants discussed their approach to ACT. Practices varied by country and between adult/pediatric care providers. MI-E is most often used in the United States, but elsewhere in the world, LVR with a self-inflating bag and one-way valve is first-line therapy. Clinical care guidelines suggest initiation of regular ACT when cough peak flow is < 270 L/minute, forced vital capacity < 40%-60% predicted, or with subjectively weak cough (Hull et al. Thorax. 2012;67(7):654-655; Amin et al. Can J Resp Crit Care Sleep Med. 2017;1(1):7-36; McKim et al. Can Resp J. 2011;18(4):197-215; Birnkrant et al. Lancet Neurol. 2018;17(4):347-361; Sheehan et al. Pediatrics. 2018;142(Suppl 2):S62-s71).
Optimal timing for initiation of routine ACT, however, is not clear. A newly published randomized controlled trial of twice daily LVR in boys with Duchenne muscular dystrophy with relatively normal baseline lung function did not demonstrate a significant slowing of decline in forced vital capacity over 2 years. In individuals with preserved lung function, the burden of regular therapy may outweigh benefit (Katz et al. Thorax. 2022; doi: 10.1136/thoraxjnl-2021-218196). (While we are still learning about how best to apply this therapy in less advanced neuromuscular disease, ACT has demonstrated benefits during respiratory exacerbations, and routine use plays a role in preservation of lung function in more advanced disease (Katz et al. Ann Am Thorac Soc. 2016;13(2):217-222; McKim et al. Arch Phys Med Rehab. 2012;93(7):1117-1122; O’Sullivan et al. Arch Phys Med Rehabil. 2021;102(5):976-983; Bach et al. Am J Phys Med Rehab. 2008;87(9):720-725).
Sherri Katz, MD, FCCP
Section Steering Committee Chair
Critical care network: Mechanical ventilation and airways management section
NIV following extubation: Which devices and which patients?
For those of us interested in studying mechanical ventilation, an interesting paradox exists: despite our interest and enthusiasm in studying it, our patients benefit from avoiding it! Patients who require re-intubation are at high risk of in-hospital mortality (Frutos-Vivar et al. J Crit Care. 2011;26:502-9). 
Studies in high-risk patients receiving mechanical ventilation have demonstrated that patients treated with immediate noninvasive ventilation (NIV) following extubation had reduced risk of re-intubation. CHEST guidelines focused on ventilator liberation considered these studies in a metanalysis which led to recommendations to employ NIV immediately after extubation in high-risk patients to reduce re-intubation rates (Ouellette D et al. Chest. 2017;151:166-80).
In the years since the publication of the CHEST guidelines, more information has been forthcoming. Evidence has emerged that treatment with high-flow nasal cannula devices following extubation may mitigate against re-intubation. An interesting strategy from the High-Wean Study Group suggested that postextubation combination therapy with both a high-flow cannula and NIV leads to improved outcomes compared with high-flow alone (Thille AW et al. JAMA. 2019;322:1465-75).
Thille and coworkers recently broadened our concept of patients who may benefit from NIV post extubation. They examined a cohort of obese patients requiring mechanical ventilation, finding that when patients were treated with NIV and high-flow nasal cannula post extubation, that they had a reduced risk of re-intubation compared with a group receiving high flow alone (Thille AW, et al. Am J Respir Crit Care Med. 2022;205:440-9).
As the incoming chair of the Mechanical Ventilation and Airways Management Section of the CHEST Critical Care Network, I look forward during the next 2 years to having interesting conversations about topics like this one and working with section members to develop exciting new projects concerning mechanical ventilation.
Daniel Ouellette, MD, MS, FCCP
Section Steering Committee Chair
Thoracic oncology and chest procedures network: Pleural disease section
Management of recurrent transudative pleural effusions (REDUCE trial)
Nonmalignant pleural effusions contribute significantly to health care costs and mortality (Mummadi SR et al. CHEST. 2021 Oct;160[4]:1534-51; Walker SP et al. CHEST. 2017 May;151[5]:1099-105). Management of transudative effusions has traditionally been to treat the underlying etiology. However, despite maximal medical therapies, these recurrent effusions may add to patients’ symptom burden and often create a challenge for the clinician. In 2017, the FDA approved the use of indwelling pleural catheters (IPC) in patients with recurrent transudative effusions, but data are limited.
In a recent prospective multicenter randomized control trial, Walker and colleagues (Eur Respir J. 2022 Feb;59:2101362) aimed to compare IPCs to repeated therapeutic thoracentesis (TT) in the management of transudative effusions. Pleural fluid etiologies included heart (68%), liver (24%), and renal failure (8%). The primary outcome was mean dyspnea score (daily visual analog scales) over 12 weeks, and there was no significant difference noted (39.7 vs. 45.0, mean difference –2.9 mm, 95% confidence interval [CI] –16.1 to 10.3; P = .67). Secondary outcomes demonstrated increased overall drainage in the IPC vs. TT group (17,412 mL vs. 2,901 mL, difference 13,892 mL, 95% CI, 7,669-20,116 mL; P < .001) and fewer invasive procedures required in the IPC group. Adverse events were noted in 59% of the IPC group compared with 37% managed with TT (OR, 3.13, 95% CI, 1.07-9.13, P = .04).
The REDUCE trial offers valuable data, but failure to meet primary outcome, study size, and adverse events highlight limitations to a definitive change in practice. Further study with specific-disease processes (ie, cardiac) may be helpful in the future. As in malignant pleural effusions, the selection of definitive pleural intervention should be tailored for each patient.
Maria Azhar, MD
Network Member-at-Large
Saadia A. Faiz, MD FCCP
Section Steering Committee Chair
Airway disorders network: Asthma and COPD section
Betting on asthma: The over and under of diagnosis
Asthma is one of the major chronic respiratory diseases worldwide (WHO 2020), yet it is a clinical syndrome that lacks a consensus on its definition, is comprised of nonspecific respiratory symptoms, and is without a gold standard diagnostic test or a set guideline on confirmation of bronchial hyperresponsiveness (Sá-Sousa A et al. Clin Transl Allergy. 2014 Aug 4;4:24). In addition, once adequately treated, there is an absence of an algorithm to diagnose disease remission (Aaron SD et al. Am J Respir Crit Care Med. 2018 Oct 15;198[8]:1012-20). It is estimated that 20%-70% of people with asthma worldwide across the spectrum of all ages remain undiagnosed.
Spirometry and bronchoprovocation challenges with fixed cut-off values demonstrate reduced sensitivity with day-to-day, diurnal, and long-term variation in airflow obstruction, inflammation, and bronchial hyperresponsiveness (Wang R et al. Thorax. 2021 Jun;76[6]:624-31). Inflammatory biomarkers like fractional exhaled nitric oxide (FeNO) have higher specificity but are subject to diurnal variation and confounding diagnoses.
Overdiagnosis of asthma can result in lost opportunity to diagnose significant cardiopulmonary diseases, unnecessary escalation of the asthma treatment regimen for poorly controlled respiratory symptoms, potential for medication adverse effects, and, increased cost burden to the patient and to the health care system (Aaron SD et al. JAMA. 2017;317:269-79; Shaw D et al. Prim Care Respir J. 2012;21:283-7). Among the newly physician-diagnosed asthmatics, <50% have spirometry performed within 1 year of diagnosis (Sokol KC et al. Am J Med. 2015 May;128[5]:502-8). Spirometry was further underutilized with limit on aerosol-generating procedures during COVID-19 pandemic (Kankaanranta H et al. J Allergy Clin Immunol Pract. 2021 Dec;9[12]:4252-3); 30%-35% obese and nonobese patients with physician-diagnosed asthma did not have current asthma when objectively assessed for airflow limitation (Aaron SD et al. JAMA. 2017;317:269-79; van Huisstede A, et al. Respir Med. 2013;107:1356-64).
Clinical remission is greater in early-onset asthma as compared with late-onset asthma (De Marco R et al. J Allergy Clin Immunol. 2002;110:228-35). If asthma is well controlled, a stepping down treatment regimen is suggested (Global Initiative for Asthma 2021;Usmani et al. J Allergy Clin Immunol Pract. 2017 Sep-Oct;5[5]:1378-87.e5; Hagan JB et al. Allergy. 2014 Apr;69[4]:510-6), and although a randomized trial is lacking, it may be feasible to “undiagnose” patients who don’t experience clinical worsening, airflow obstruction, or bronchial hyperresponsiveness after being tapered off all asthma medications with a low relapse rate (Aaron SD et al. JAMA. 2017;317:269-79; J Fam Pract. 2018;67(11):704-7).
Asthma over- and underdiagnosis is prevalent and has clinical and global health consequences. New standardized algorithms with improved biomarkers may help alter this oversight.
Richa Nahar, MD
Network Member-at-Large
Allen J. Blaivas, DO, FCCP
Network Steering Committee Chair
Diffuse lung disease and lung transplant network: Interstitial lung disease section
Future therapies for IPF
Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by progressive fibrosis, respiratory failure, and a mortality rate of 80% at 5 years. Only two drugs are currently FDA-approved for IPF treatment.
The antifibrotics pirfenidone and nintedanib reduce the rate of forced vital capacity (FVC) decline and improve progression free survival (King TE et al. N Engl J Med. 2014;370:2083-92; King TE et al. N Engl J Med. 2014;370:2071-82). While considered revolutionary when introduced, these medications neither reverse disease progression nor improve symptoms. More recently, the Galapagos ISABELA Phase III clinical trial of ziritaxestat in IPF was discontinued due to an unfavorable risk-benefit profile. Despite this, several prospects for IPF therapy exist.
Post hoc analysis of the INCREASE Trial demonstrated a positive effect of inhaled treprostinil on FVC in patients with IPF and group 3 pulmonary hypertension (Waxman A et al. N Engl J Med. 2021;384:325-34). Consequently, a phase 3 randomized trial investigating its safety and efficacy in patients with IPF alone is ongoing. Additional targeted therapies for IPF are also emerging. Recombinant human pentraxin-2, an inhibitor of monocyte differentiation into proinflammatory macrophages, and pamrevlumab, a recombinant human monoclonal antibody against connective tissue growth factor, both demonstrated attenuation of FVC decline compared with placebo in phase 2 trials. Both are currently in phase 3 studies (Raghu G et al. JAMA. 2018 Jun 12;319[22]:2299-307; Sgalla G et al. Expert Opin Investig Drugs. 2020 Aug;29[8]:771-7) Lastly, in February the Food and Drug Administration granted breakthrough therapy designation to BI 1015550 for treatment of IPF based on a 12-week phase 2 randomized, double-blind, placebo-controlled trial. (Data will be presented at ATS). BI 1015550 is an oral, phosphodiesterase 4B (PDE4B) inhibitor with both antifibrotic and anti-inflammatory properties. These advances in drug development provide hope for a future where IPF is transformed from a fatal disease to one manageable over many years.
Adrian Shifren, MD
Network Member-at-Large
Gabriel Schroeder, MD
Network Member-at-Large
Sleep medicine network: Home-based mechanical ventilation and neuromuscular section
Role of airway clearance therapies in neuromuscular disease
Individuals with neuromuscular weakness have an impaired ability to cough and clear secretions from the airway, which can result in atelectasis and pneumonia. Proximal airway clearance therapies (ACT), including manual lung volume recruitment (LVR) and mechanical in-exsufflation (MI-E), mobilize secretions, improve cough efficacy, maintain chest wall compliance, and slow progression of restrictive lung impairment (Chatwin et al. Respir Med. 2018;136:98-110; Sheers et al. Respirology. 2019;24:512-520).
ACT are recommended in international care guidelines for respiratory management of individuals with neuromuscular disease. At a recent Home-based Mechanical Ventilation and Neuromuscular Disease Section “PEEPS Talking PAP” rounds, participants discussed their approach to ACT. Practices varied by country and between adult/pediatric care providers. MI-E is most often used in the United States, but elsewhere in the world, LVR with a self-inflating bag and one-way valve is first-line therapy. Clinical care guidelines suggest initiation of regular ACT when cough peak flow is < 270 L/minute, forced vital capacity < 40%-60% predicted, or with subjectively weak cough (Hull et al. Thorax. 2012;67(7):654-655; Amin et al. Can J Resp Crit Care Sleep Med. 2017;1(1):7-36; McKim et al. Can Resp J. 2011;18(4):197-215; Birnkrant et al. Lancet Neurol. 2018;17(4):347-361; Sheehan et al. Pediatrics. 2018;142(Suppl 2):S62-s71).
Optimal timing for initiation of routine ACT, however, is not clear. A newly published randomized controlled trial of twice daily LVR in boys with Duchenne muscular dystrophy with relatively normal baseline lung function did not demonstrate a significant slowing of decline in forced vital capacity over 2 years. In individuals with preserved lung function, the burden of regular therapy may outweigh benefit (Katz et al. Thorax. 2022; doi: 10.1136/thoraxjnl-2021-218196). (While we are still learning about how best to apply this therapy in less advanced neuromuscular disease, ACT has demonstrated benefits during respiratory exacerbations, and routine use plays a role in preservation of lung function in more advanced disease (Katz et al. Ann Am Thorac Soc. 2016;13(2):217-222; McKim et al. Arch Phys Med Rehab. 2012;93(7):1117-1122; O’Sullivan et al. Arch Phys Med Rehabil. 2021;102(5):976-983; Bach et al. Am J Phys Med Rehab. 2008;87(9):720-725).
Sherri Katz, MD, FCCP
Section Steering Committee Chair
Critical care network: Mechanical ventilation and airways management section
NIV following extubation: Which devices and which patients?
For those of us interested in studying mechanical ventilation, an interesting paradox exists: despite our interest and enthusiasm in studying it, our patients benefit from avoiding it! Patients who require re-intubation are at high risk of in-hospital mortality (Frutos-Vivar et al. J Crit Care. 2011;26:502-9).
Studies in high-risk patients receiving mechanical ventilation have demonstrated that patients treated with immediate noninvasive ventilation (NIV) following extubation had reduced risk of re-intubation. CHEST guidelines focused on ventilator liberation considered these studies in a metanalysis which led to recommendations to employ NIV immediately after extubation in high-risk patients to reduce re-intubation rates (Ouellette D et al. Chest. 2017;151:166-80).
In the years since the publication of the CHEST guidelines, more information has been forthcoming. Evidence has emerged that treatment with high-flow nasal cannula devices following extubation may mitigate against re-intubation. An interesting strategy from the High-Wean Study Group suggested that postextubation combination therapy with both a high-flow cannula and NIV leads to improved outcomes compared with high-flow alone (Thille AW et al. JAMA. 2019;322:1465-75).
Thille and coworkers recently broadened our concept of patients who may benefit from NIV post extubation. They examined a cohort of obese patients requiring mechanical ventilation, finding that when patients were treated with NIV and high-flow nasal cannula post extubation, that they had a reduced risk of re-intubation compared with a group receiving high flow alone (Thille AW, et al. Am J Respir Crit Care Med. 2022;205:440-9).
As the incoming chair of the Mechanical Ventilation and Airways Management Section of the CHEST Critical Care Network, I look forward during the next 2 years to having interesting conversations about topics like this one and working with section members to develop exciting new projects concerning mechanical ventilation.
Daniel Ouellette, MD, MS, FCCP
Section Steering Committee Chair
Thoracic oncology and chest procedures network: Pleural disease section
Management of recurrent transudative pleural effusions (REDUCE trial)
Nonmalignant pleural effusions contribute significantly to health care costs and mortality (Mummadi SR et al. CHEST. 2021 Oct;160[4]:1534-51; Walker SP et al. CHEST. 2017 May;151[5]:1099-105). Management of transudative effusions has traditionally been to treat the underlying etiology. However, despite maximal medical therapies, these recurrent effusions may add to patients’ symptom burden and often create a challenge for the clinician. In 2017, the FDA approved the use of indwelling pleural catheters (IPC) in patients with recurrent transudative effusions, but data are limited.
In a recent prospective multicenter randomized control trial, Walker and colleagues (Eur Respir J. 2022 Feb;59:2101362) aimed to compare IPCs to repeated therapeutic thoracentesis (TT) in the management of transudative effusions. Pleural fluid etiologies included heart (68%), liver (24%), and renal failure (8%). The primary outcome was mean dyspnea score (daily visual analog scales) over 12 weeks, and there was no significant difference noted (39.7 vs. 45.0, mean difference –2.9 mm, 95% confidence interval [CI] –16.1 to 10.3; P = .67). Secondary outcomes demonstrated increased overall drainage in the IPC vs. TT group (17,412 mL vs. 2,901 mL, difference 13,892 mL, 95% CI, 7,669-20,116 mL; P < .001) and fewer invasive procedures required in the IPC group. Adverse events were noted in 59% of the IPC group compared with 37% managed with TT (OR, 3.13, 95% CI, 1.07-9.13, P = .04).
The REDUCE trial offers valuable data, but failure to meet primary outcome, study size, and adverse events highlight limitations to a definitive change in practice. Further study with specific-disease processes (ie, cardiac) may be helpful in the future. As in malignant pleural effusions, the selection of definitive pleural intervention should be tailored for each patient.
Maria Azhar, MD
Network Member-at-Large
Saadia A. Faiz, MD FCCP
Section Steering Committee Chair
Airway disorders network: Asthma and COPD section
Betting on asthma: The over and under of diagnosis
Asthma is one of the major chronic respiratory diseases worldwide (WHO 2020), yet it is a clinical syndrome that lacks a consensus on its definition, is comprised of nonspecific respiratory symptoms, and is without a gold standard diagnostic test or a set guideline on confirmation of bronchial hyperresponsiveness (Sá-Sousa A et al. Clin Transl Allergy. 2014 Aug 4;4:24). In addition, once adequately treated, there is an absence of an algorithm to diagnose disease remission (Aaron SD et al. Am J Respir Crit Care Med. 2018 Oct 15;198[8]:1012-20). It is estimated that 20%-70% of people with asthma worldwide across the spectrum of all ages remain undiagnosed.
Spirometry and bronchoprovocation challenges with fixed cut-off values demonstrate reduced sensitivity with day-to-day, diurnal, and long-term variation in airflow obstruction, inflammation, and bronchial hyperresponsiveness (Wang R et al. Thorax. 2021 Jun;76[6]:624-31). Inflammatory biomarkers like fractional exhaled nitric oxide (FeNO) have higher specificity but are subject to diurnal variation and confounding diagnoses.
Overdiagnosis of asthma can result in lost opportunity to diagnose significant cardiopulmonary diseases, unnecessary escalation of the asthma treatment regimen for poorly controlled respiratory symptoms, potential for medication adverse effects, and, increased cost burden to the patient and to the health care system (Aaron SD et al. JAMA. 2017;317:269-79; Shaw D et al. Prim Care Respir J. 2012;21:283-7). Among the newly physician-diagnosed asthmatics, <50% have spirometry performed within 1 year of diagnosis (Sokol KC et al. Am J Med. 2015 May;128[5]:502-8). Spirometry was further underutilized with limit on aerosol-generating procedures during COVID-19 pandemic (Kankaanranta H et al. J Allergy Clin Immunol Pract. 2021 Dec;9[12]:4252-3); 30%-35% obese and nonobese patients with physician-diagnosed asthma did not have current asthma when objectively assessed for airflow limitation (Aaron SD et al. JAMA. 2017;317:269-79; van Huisstede A, et al. Respir Med. 2013;107:1356-64).
Clinical remission is greater in early-onset asthma as compared with late-onset asthma (De Marco R et al. J Allergy Clin Immunol. 2002;110:228-35). If asthma is well controlled, a stepping down treatment regimen is suggested (Global Initiative for Asthma 2021;Usmani et al. J Allergy Clin Immunol Pract. 2017 Sep-Oct;5[5]:1378-87.e5; Hagan JB et al. Allergy. 2014 Apr;69[4]:510-6), and although a randomized trial is lacking, it may be feasible to “undiagnose” patients who don’t experience clinical worsening, airflow obstruction, or bronchial hyperresponsiveness after being tapered off all asthma medications with a low relapse rate (Aaron SD et al. JAMA. 2017;317:269-79; J Fam Pract. 2018;67(11):704-7).
Asthma over- and underdiagnosis is prevalent and has clinical and global health consequences. New standardized algorithms with improved biomarkers may help alter this oversight.
Richa Nahar, MD
Network Member-at-Large
Allen J. Blaivas, DO, FCCP
Network Steering Committee Chair
Diffuse lung disease and lung transplant network: Interstitial lung disease section
Future therapies for IPF
Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by progressive fibrosis, respiratory failure, and a mortality rate of 80% at 5 years. Only two drugs are currently FDA-approved for IPF treatment.
The antifibrotics pirfenidone and nintedanib reduce the rate of forced vital capacity (FVC) decline and improve progression free survival (King TE et al. N Engl J Med. 2014;370:2083-92; King TE et al. N Engl J Med. 2014;370:2071-82). While considered revolutionary when introduced, these medications neither reverse disease progression nor improve symptoms. More recently, the Galapagos ISABELA Phase III clinical trial of ziritaxestat in IPF was discontinued due to an unfavorable risk-benefit profile. Despite this, several prospects for IPF therapy exist.
Post hoc analysis of the INCREASE Trial demonstrated a positive effect of inhaled treprostinil on FVC in patients with IPF and group 3 pulmonary hypertension (Waxman A et al. N Engl J Med. 2021;384:325-34). Consequently, a phase 3 randomized trial investigating its safety and efficacy in patients with IPF alone is ongoing. Additional targeted therapies for IPF are also emerging. Recombinant human pentraxin-2, an inhibitor of monocyte differentiation into proinflammatory macrophages, and pamrevlumab, a recombinant human monoclonal antibody against connective tissue growth factor, both demonstrated attenuation of FVC decline compared with placebo in phase 2 trials. Both are currently in phase 3 studies (Raghu G et al. JAMA. 2018 Jun 12;319[22]:2299-307; Sgalla G et al. Expert Opin Investig Drugs. 2020 Aug;29[8]:771-7) Lastly, in February the Food and Drug Administration granted breakthrough therapy designation to BI 1015550 for treatment of IPF based on a 12-week phase 2 randomized, double-blind, placebo-controlled trial. (Data will be presented at ATS). BI 1015550 is an oral, phosphodiesterase 4B (PDE4B) inhibitor with both antifibrotic and anti-inflammatory properties. These advances in drug development provide hope for a future where IPF is transformed from a fatal disease to one manageable over many years.
Adrian Shifren, MD
Network Member-at-Large
Gabriel Schroeder, MD
Network Member-at-Large
Sleep medicine network: Home-based mechanical ventilation and neuromuscular section
Role of airway clearance therapies in neuromuscular disease
Individuals with neuromuscular weakness have an impaired ability to cough and clear secretions from the airway, which can result in atelectasis and pneumonia. Proximal airway clearance therapies (ACT), including manual lung volume recruitment (LVR) and mechanical in-exsufflation (MI-E), mobilize secretions, improve cough efficacy, maintain chest wall compliance, and slow progression of restrictive lung impairment (Chatwin et al. Respir Med. 2018;136:98-110; Sheers et al. Respirology. 2019;24:512-520).
ACT are recommended in international care guidelines for respiratory management of individuals with neuromuscular disease. At a recent Home-based Mechanical Ventilation and Neuromuscular Disease Section “PEEPS Talking PAP” rounds, participants discussed their approach to ACT. Practices varied by country and between adult/pediatric care providers. MI-E is most often used in the United States, but elsewhere in the world, LVR with a self-inflating bag and one-way valve is first-line therapy. Clinical care guidelines suggest initiation of regular ACT when cough peak flow is < 270 L/minute, forced vital capacity < 40%-60% predicted, or with subjectively weak cough (Hull et al. Thorax. 2012;67(7):654-655; Amin et al. Can J Resp Crit Care Sleep Med. 2017;1(1):7-36; McKim et al. Can Resp J. 2011;18(4):197-215; Birnkrant et al. Lancet Neurol. 2018;17(4):347-361; Sheehan et al. Pediatrics. 2018;142(Suppl 2):S62-s71).
Optimal timing for initiation of routine ACT, however, is not clear. A newly published randomized controlled trial of twice daily LVR in boys with Duchenne muscular dystrophy with relatively normal baseline lung function did not demonstrate a significant slowing of decline in forced vital capacity over 2 years. In individuals with preserved lung function, the burden of regular therapy may outweigh benefit (Katz et al. Thorax. 2022; doi: 10.1136/thoraxjnl-2021-218196). (While we are still learning about how best to apply this therapy in less advanced neuromuscular disease, ACT has demonstrated benefits during respiratory exacerbations, and routine use plays a role in preservation of lung function in more advanced disease (Katz et al. Ann Am Thorac Soc. 2016;13(2):217-222; McKim et al. Arch Phys Med Rehab. 2012;93(7):1117-1122; O’Sullivan et al. Arch Phys Med Rehabil. 2021;102(5):976-983; Bach et al. Am J Phys Med Rehab. 2008;87(9):720-725).
Sherri Katz, MD, FCCP
Section Steering Committee Chair
Critical care network: Mechanical ventilation and airways management section
NIV following extubation: Which devices and which patients?
For those of us interested in studying mechanical ventilation, an interesting paradox exists: despite our interest and enthusiasm in studying it, our patients benefit from avoiding it! Patients who require re-intubation are at high risk of in-hospital mortality (Frutos-Vivar et al. J Crit Care. 2011;26:502-9).
Studies in high-risk patients receiving mechanical ventilation have demonstrated that patients treated with immediate noninvasive ventilation (NIV) following extubation had reduced risk of re-intubation. CHEST guidelines focused on ventilator liberation considered these studies in a metanalysis which led to recommendations to employ NIV immediately after extubation in high-risk patients to reduce re-intubation rates (Ouellette D et al. Chest. 2017;151:166-80).
In the years since the publication of the CHEST guidelines, more information has been forthcoming. Evidence has emerged that treatment with high-flow nasal cannula devices following extubation may mitigate against re-intubation. An interesting strategy from the High-Wean Study Group suggested that postextubation combination therapy with both a high-flow cannula and NIV leads to improved outcomes compared with high-flow alone (Thille AW et al. JAMA. 2019;322:1465-75).
Thille and coworkers recently broadened our concept of patients who may benefit from NIV post extubation. They examined a cohort of obese patients requiring mechanical ventilation, finding that when patients were treated with NIV and high-flow nasal cannula post extubation, that they had a reduced risk of re-intubation compared with a group receiving high flow alone (Thille AW, et al. Am J Respir Crit Care Med. 2022;205:440-9).
As the incoming chair of the Mechanical Ventilation and Airways Management Section of the CHEST Critical Care Network, I look forward during the next 2 years to having interesting conversations about topics like this one and working with section members to develop exciting new projects concerning mechanical ventilation.
Daniel Ouellette, MD, MS, FCCP
Section Steering Committee Chair
Thoracic oncology and chest procedures network: Pleural disease section
Management of recurrent transudative pleural effusions (REDUCE trial)
Nonmalignant pleural effusions contribute significantly to health care costs and mortality (Mummadi SR et al. CHEST. 2021 Oct;160[4]:1534-51; Walker SP et al. CHEST. 2017 May;151[5]:1099-105). Management of transudative effusions has traditionally been to treat the underlying etiology. However, despite maximal medical therapies, these recurrent effusions may add to patients’ symptom burden and often create a challenge for the clinician. In 2017, the FDA approved the use of indwelling pleural catheters (IPC) in patients with recurrent transudative effusions, but data are limited.
In a recent prospective multicenter randomized control trial, Walker and colleagues (Eur Respir J. 2022 Feb;59:2101362) aimed to compare IPCs to repeated therapeutic thoracentesis (TT) in the management of transudative effusions. Pleural fluid etiologies included heart (68%), liver (24%), and renal failure (8%). The primary outcome was mean dyspnea score (daily visual analog scales) over 12 weeks, and there was no significant difference noted (39.7 vs. 45.0, mean difference –2.9 mm, 95% confidence interval [CI] –16.1 to 10.3; P = .67). Secondary outcomes demonstrated increased overall drainage in the IPC vs. TT group (17,412 mL vs. 2,901 mL, difference 13,892 mL, 95% CI, 7,669-20,116 mL; P < .001) and fewer invasive procedures required in the IPC group. Adverse events were noted in 59% of the IPC group compared with 37% managed with TT (OR, 3.13, 95% CI, 1.07-9.13, P = .04).
The REDUCE trial offers valuable data, but failure to meet primary outcome, study size, and adverse events highlight limitations to a definitive change in practice. Further study with specific-disease processes (ie, cardiac) may be helpful in the future. As in malignant pleural effusions, the selection of definitive pleural intervention should be tailored for each patient.
Maria Azhar, MD
Network Member-at-Large
Saadia A. Faiz, MD FCCP
Section Steering Committee Chair