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Interventional Chest/Diagnostic Procedures
Cryobiopsy for ILD: Careful stewardship needed
Interest in transbronchial cryobiopsy has accelerated rapidly in recent years. This procedure is performed by advancing a cryoprobe into the peripheral lung via flexible bronchoscopy, where lung tissue freezes and adheres to the probe and is subsequently extracted as a cryobiopsy. The number of cryobiopsy-related publications has increased exponentially since it was described in 2009 (Babiak A, et al. Respiration. 2009;78[2]:203). This interest stems from reports of high diagnostic yields in patients with interstitial lung disease (ILD) while maintaining complication rates similar to that of conventional bronchoscopic biopsy. 
Traditional bronchoscopic biopsies are notoriously insensitive; a specific diagnosis can be established in fewer than a third of cases (Sheth JS, et al. Chest. 2017;151[2]:389). As such, surgical lung biopsy continues to be recommended but is associated with significant mortality (2%) and morbidity (30%) in patients with ILD (Hutchinson JP, et al. ARJCCM. 2016;193[10]:1161). Cryobiopsy, which appears to rival surgical lung biopsy in terms of ability to contribute to a specific diagnosis, is, therefore, a highly promising alternative (Tomassetti S, et al. AJRCCM. 2016;193[7]:745).
As cryobiopsy is increasingly adopted around the world, however, troubling reports of serious complications have surfaced. Most notable is the recently reported experience of the initial 25 cases performed at the University of Pennsylvania, in which almost one in four patients suffered serious complications (DiBardino DM, et al. Ann Am Thorac Soc. 2017;14[6]:851). The authors pointed to lack of a predefined procedural protocol, as well as several choices relating to the specific technique used, including inconsistent use of fluoroscopy, lack of prophylactic bronchial blocker placement, and predominant use of laryngeal mask airways as potential contributing factors. Indeed, many variations of the basic cryobiopsy procedure have been described (Lentz RJ, et al. J Thoracic Dis. 2017;9[7]:2186), with no formal guidance or training available to inform advanced bronchoscopists interested in this procedure.
It is incumbent on the interventional pulmonology and ILD specialist communities to be responsible stewards of this promising procedure. Implementation of three parallel efforts to standardize and rigorously study this procedure should be considered as soon as possible: creation of expert consensus guidelines establishing best-practices for safe and effective biopsy technique; a training requirement before independent performance of the procedure; and creation of an international cryobiopsy registry to facilitate higher-quality research into optimal technique and outcomes. We owe this to our patients.
Robert J. Lentz, MD
NetWork Member
Fabien Maldonado, MD, FCCP
NetWork Member
Pediatric Chest Medicine
Chronic cough in children: New guidelines
A chronic cough is a common complaint among children whose parents seek medical evaluation. Chronic wet cough can indicate an underlying illness; therefore, an early diagnosis can lead to prevention of complications of the disease and improvement in quality of life.
CHEST is a leading resource in evidence and consensus-based guidelines on important topics affecting children. The most recent guidelines entitled Management of Children with Chronic Wet Cough and Protracted Bacterial Bronchitis (Chest. 2017;151(4):884-890) and Use of Management Pathways or Algorithms in Children with Chronic Cough (Chest. 2017;151(4):875-873) are updates from the 2006 CHEST guidelines on chronic cough in children.
The present updates utilized the CHEST methodological guidelines with chronic wet or productive cough and Grading of Recommendations Assessment, Development, and Evaluation framework and also performed a systematic review addressing key questions concerning the management of childhood disease for children 14 years and younger.
Guidance provided by the expert panel focused on recommendations to answer six key questions concerning the management of children 14 years and younger with a chronic wet cough unrelated to established chronic lung disease. The recommendations are:
1. Chronic cough is defined as the presence of a cough 4 weeks or longer in duration.
2. Assessment of the effect of the cough on the child and the family be undertaken as part of clinical consultation.
3. Evaluation of a chronic cough should be done with a systematic approach with pediatric-specific cough management protocols or algorithms.
4. Chest radiograph and, when age appropriate, spirometry with bronchodilator be undertaken as evaluation; tests for pertussis infection only to be performed if clinically suspected.
5. Chronic wet cough with no specific clinical features should receive antibiotics for 2 weeks targeted for common respiratory bacteria (Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis).
6. When cough persists despite 2 weeks of appropriate antibiotics, it is recommended to continue for an additional 2 weeks.
7. Additional tests (eg skin prick test, Mantoux, bronchoscopy, chest CT scan) should be individualized in accordance with the clinical setting and child’s clinical symptoms and signs.
The panel recognizes the need for prospective studies to assess current algorithms outcomes of children with chronic cough. Both articles can be found on the guidelines section of the CHEST site.
John Bishara, DO
Fellow-in-Training Member
Pulmonary Physiology, Function, and Rehabilitation
Functional imaging of the lung
Quantifying heterogeneity of ventilation and gas exchange in lung diseases remains a clinical challenge. Conventional pulmonary function test is insensitive to regional changes. The multiple inert gas elimination technique can quantify ventilation-perfusion distribution, but it requires invasive instrumentation (eg, pulmonary artery catheterization) and is not practical for clinical use. Computed tomography (CT) scans delineate spatial changes in lung structures but do not directly measure changes in ventilation and gas exchange. With its radiation, it is difficult to apply CT scanning repeatedly in patients. More recently, MR imaging techniques have been developed to directly “visualize” and quantify regional lung function (Kruger SJ, et al. J Magn Reson Imaging. 2016;43(2):295; Roos JE, et al. Magn Reson Imaging Clin N Am. 2015;23(2):217). These techniques employ inhalation of gases, such as oxygen, perfluorinated gases, and hyperpolarized 3He and 129Xe. Hyperpolarized 3He has been studied the most; however, the dwindling supply of 3He gas and its rising cost have prevented its further development. 129Xe has abundant supply and has emerged to be the inert gas of choice for MR imaging. Hyperpolarized 129Xe can measure ventilation, like hyperpolarized 3He. In addition, Xe diffuses into alveolar barrier (interstitium and plasma) and red blood cells, where it exhibits distinct resonant frequency shifts that can be captured by MR. Therefore, in one test, information on pulmonary ventilation and gas transfer can be obtained. To date, the results from MR imaging studies have provided new insights into the pathophysiology of obstructive and restrictive lung diseases. With continuous development, MR imaging of the lung could become a clinically useful tool in the near future.
Yuh-Chin T. Huang, MD, MHS, FCCP
Steering Committee Member
Thoracic Oncology
Immune-mediated pneumonitis and PD-1 inhibition
Inhibitors of the programmed cell death 1 receptor (PD-1) have shown significant promise in the treatment of advanced stage malignancy. With the recent expansion of indications for use of these agents, the number of patients treated will continue to grow. Clinicians must be aware of their potential for serious adverse side effects, including dermatitis, colitis, and potentially life-threatening pneumonitis.
The development of pneumonitis secondary to PD-1 inhibitions is reported to occur in 2% to 5% of patients and can present at any time during therapy, with 1% of patients developing grade 3 or higher pneumonitis.1,2 The most common symptoms are dyspnea and cough, though one-third of patients are asymptomatic at presentation.2 Radiographic and pathologic features vary greatly and include organizing pneumonia, interstitial pneumonitis, hypersensitivity pneumonitis, or diffuse alveolar damage.3 While pneumonitis due to PD-1 inhibition is reportedly uncommon, the increasing number of patients expected to receive these medications will predictably result in increasing overall frequency of pneumonitis cases. In addition, the lack of large prospective randomized trials and reliance on radiographic rather than pathologic data in diagnosing immune-mediated pneumonitis gives one pause. Given the variability of presentation, lack of routine pathologic data, and increasing use of dual agents (eg, PD-1 and CTLA-4), chest physicians and medical oncologists should have a high index of suspicion yet practice equipoise in patients receiving immunotherapy who develop unexplained pulmonary symptoms or infiltrates. More research is needed to help improve the multidisciplinary diagnosis and treatment of this potentially serious complication.
David Maurice Chambers, MD
Fellow-in-Training Member
Jason Atticus Akulian, MD, MPH
Steering Committee Member
References
1. Nishino M, et al. Incidence of programmed cell death 1 inhibitor-related pneumonitis in patients with advanced cancer: a systematic review and meta-analysis. JAMA Oncology. 2016;2(12):1607.
2. Naidoo J, et al. Pneumonitis in patients treated with anti-programmed death-1/programmed death ligand 1 therapy. J Clin Oncol. 2017;35(7):709.
3. Nishino M, et al. PD-1 inhibitor-related pneumonitis in advanced cancer patients: radiographic patterns and clinical course. Clin Cancer Res. 2016;22(24):6051.
Pulmonary Vascular Disease
Pulmonary Arterial Hypertension Associated With SLE
While pulmonary arterial hypertension (PAH) commonly complicates scleroderma (SSc), it is a rare complication of other connective tissue diseases (CTD), such as systemic lupus erythematosus (SLE). In the few prospective studies that utilize right-sided heart catheterization (RHC), the estimated prevalence of PAH in SLE is about 4%. However, since the prevalence of SLE is 10 to 15 times greater than SSc in the United States, the true prevalence of SLE-PAH may be higher than previously thought, and, thus, clinically relevant. Despite this, little is known about SLE-PAH.
A recent retrospective study from the French Pulmonary Hypertension Registry has added significantly to our understanding of this complication of SLE. Hachulla and colleagues studied 51 patients with RHC-proven SLE-PAH compared with 101 SLE control subjects without PAH. While the authors did not find any relevant differences in the demographics between groups, they did find a significantly higher prevalence of SSA and SSB antibodies in SLE-PAH. Interestingly, the presence of anti-U1 RNP antibody appeared to be less common in SLE-PAH patients; this lack of association is in contrast to prior studies in mixed CTD patients with anti-U1 RNP antibodies in which the prevalence of PAH can be as high as 60%. Further, none of the SLE-PAH patients demonstrated an acute response to vasodilator challenge during RHC, emphasizing that this maneuver does not need to be performed in SLE patients at risk of PAH. Trends toward improved survival in SLE-PAH patients treated with hydroxychloroquine are preliminary and hypothesis-generating but require confirmation in larger clinical studies.
Stephen Mathai, MD, FCCP
Chair
Leena Palwar, MD
Fellow-in-Training Member
Hachulla E, Jais X, Cinquetti G, et al. Pulmonary arterial hypertension associated with SLE: Results from the French pulmonary hypertension registry. Chest. 2017 Aug 26. pii: S0012-3692(17)31430-7. doi: 10.1016/j.chest.2017.08.014. [Epub ahead of print]
Chung L, Liu J, Parsons L, et al. Characterization of connective tissue disease-associated pulmonary arterial hypertension from REVEAL: identifying systemic sclerosis as a unique phenotype. Chest. 2010;138:1383-1394.
Shirai Y, Yasuoka H, Okano Y, Takeuchi T, Satoh T, Kuwana M. Clinical characteristics and survival of Japanese patients with connective tissue disease and pulmonary arterial hypertension: a singlecentre cohort. Rheumatology. 2012;51:1846-1854.
Hao YJ, Jiang X, Zhou W, et al. Connective tissue disease-associated pulmonary arterial hypertension in Chinese patients. Eur Respir J. 2014;44: 963-972.
Huang C, Li M, Liu Y, et al. Baseline characteristics and risk factors of pulmonary arterial hypertension in systemic lupus erythematosus patients. Medicine. 2016;95:e2761.
Pérez-Peñate GM, Rúa-Figueroa I, Juliá- Serdá G, et al. Pulmonary arterial hypertension in systemic lupus erythematosus: prevalence and predictors. J Rheumatol. 2016;43:323-329.
Alpert MA, Goldberg SH, Sindem BH, et al. Cardiovascular manifestations of mixed connective tissue disease in adults. Circulation. 1983;63:1182-1193.
Interventional Chest/Diagnostic Procedures
Cryobiopsy for ILD: Careful stewardship needed
Interest in transbronchial cryobiopsy has accelerated rapidly in recent years. This procedure is performed by advancing a cryoprobe into the peripheral lung via flexible bronchoscopy, where lung tissue freezes and adheres to the probe and is subsequently extracted as a cryobiopsy. The number of cryobiopsy-related publications has increased exponentially since it was described in 2009 (Babiak A, et al. Respiration. 2009;78[2]:203). This interest stems from reports of high diagnostic yields in patients with interstitial lung disease (ILD) while maintaining complication rates similar to that of conventional bronchoscopic biopsy.
Traditional bronchoscopic biopsies are notoriously insensitive; a specific diagnosis can be established in fewer than a third of cases (Sheth JS, et al. Chest. 2017;151[2]:389). As such, surgical lung biopsy continues to be recommended but is associated with significant mortality (2%) and morbidity (30%) in patients with ILD (Hutchinson JP, et al. ARJCCM. 2016;193[10]:1161). Cryobiopsy, which appears to rival surgical lung biopsy in terms of ability to contribute to a specific diagnosis, is, therefore, a highly promising alternative (Tomassetti S, et al. AJRCCM. 2016;193[7]:745).
As cryobiopsy is increasingly adopted around the world, however, troubling reports of serious complications have surfaced. Most notable is the recently reported experience of the initial 25 cases performed at the University of Pennsylvania, in which almost one in four patients suffered serious complications (DiBardino DM, et al. Ann Am Thorac Soc. 2017;14[6]:851). The authors pointed to lack of a predefined procedural protocol, as well as several choices relating to the specific technique used, including inconsistent use of fluoroscopy, lack of prophylactic bronchial blocker placement, and predominant use of laryngeal mask airways as potential contributing factors. Indeed, many variations of the basic cryobiopsy procedure have been described (Lentz RJ, et al. J Thoracic Dis. 2017;9[7]:2186), with no formal guidance or training available to inform advanced bronchoscopists interested in this procedure.
It is incumbent on the interventional pulmonology and ILD specialist communities to be responsible stewards of this promising procedure. Implementation of three parallel efforts to standardize and rigorously study this procedure should be considered as soon as possible: creation of expert consensus guidelines establishing best-practices for safe and effective biopsy technique; a training requirement before independent performance of the procedure; and creation of an international cryobiopsy registry to facilitate higher-quality research into optimal technique and outcomes. We owe this to our patients.
Robert J. Lentz, MD
NetWork Member
Fabien Maldonado, MD, FCCP
NetWork Member
Pediatric Chest Medicine
Chronic cough in children: New guidelines
A chronic cough is a common complaint among children whose parents seek medical evaluation. Chronic wet cough can indicate an underlying illness; therefore, an early diagnosis can lead to prevention of complications of the disease and improvement in quality of life.
CHEST is a leading resource in evidence and consensus-based guidelines on important topics affecting children. The most recent guidelines entitled Management of Children with Chronic Wet Cough and Protracted Bacterial Bronchitis (Chest. 2017;151(4):884-890) and Use of Management Pathways or Algorithms in Children with Chronic Cough (Chest. 2017;151(4):875-873) are updates from the 2006 CHEST guidelines on chronic cough in children.
The present updates utilized the CHEST methodological guidelines with chronic wet or productive cough and Grading of Recommendations Assessment, Development, and Evaluation framework and also performed a systematic review addressing key questions concerning the management of childhood disease for children 14 years and younger.
Guidance provided by the expert panel focused on recommendations to answer six key questions concerning the management of children 14 years and younger with a chronic wet cough unrelated to established chronic lung disease. The recommendations are:
1. Chronic cough is defined as the presence of a cough 4 weeks or longer in duration.
2. Assessment of the effect of the cough on the child and the family be undertaken as part of clinical consultation.
3. Evaluation of a chronic cough should be done with a systematic approach with pediatric-specific cough management protocols or algorithms.
4. Chest radiograph and, when age appropriate, spirometry with bronchodilator be undertaken as evaluation; tests for pertussis infection only to be performed if clinically suspected.
5. Chronic wet cough with no specific clinical features should receive antibiotics for 2 weeks targeted for common respiratory bacteria (Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis).
6. When cough persists despite 2 weeks of appropriate antibiotics, it is recommended to continue for an additional 2 weeks.
7. Additional tests (eg skin prick test, Mantoux, bronchoscopy, chest CT scan) should be individualized in accordance with the clinical setting and child’s clinical symptoms and signs.
The panel recognizes the need for prospective studies to assess current algorithms outcomes of children with chronic cough. Both articles can be found on the guidelines section of the CHEST site.
John Bishara, DO
Fellow-in-Training Member
Pulmonary Physiology, Function, and Rehabilitation
Functional imaging of the lung
Quantifying heterogeneity of ventilation and gas exchange in lung diseases remains a clinical challenge. Conventional pulmonary function test is insensitive to regional changes. The multiple inert gas elimination technique can quantify ventilation-perfusion distribution, but it requires invasive instrumentation (eg, pulmonary artery catheterization) and is not practical for clinical use. Computed tomography (CT) scans delineate spatial changes in lung structures but do not directly measure changes in ventilation and gas exchange. With its radiation, it is difficult to apply CT scanning repeatedly in patients. More recently, MR imaging techniques have been developed to directly “visualize” and quantify regional lung function (Kruger SJ, et al. J Magn Reson Imaging. 2016;43(2):295; Roos JE, et al. Magn Reson Imaging Clin N Am. 2015;23(2):217). These techniques employ inhalation of gases, such as oxygen, perfluorinated gases, and hyperpolarized 3He and 129Xe. Hyperpolarized 3He has been studied the most; however, the dwindling supply of 3He gas and its rising cost have prevented its further development. 129Xe has abundant supply and has emerged to be the inert gas of choice for MR imaging. Hyperpolarized 129Xe can measure ventilation, like hyperpolarized 3He. In addition, Xe diffuses into alveolar barrier (interstitium and plasma) and red blood cells, where it exhibits distinct resonant frequency shifts that can be captured by MR. Therefore, in one test, information on pulmonary ventilation and gas transfer can be obtained. To date, the results from MR imaging studies have provided new insights into the pathophysiology of obstructive and restrictive lung diseases. With continuous development, MR imaging of the lung could become a clinically useful tool in the near future.
Yuh-Chin T. Huang, MD, MHS, FCCP
Steering Committee Member
Thoracic Oncology
Immune-mediated pneumonitis and PD-1 inhibition
Inhibitors of the programmed cell death 1 receptor (PD-1) have shown significant promise in the treatment of advanced stage malignancy. With the recent expansion of indications for use of these agents, the number of patients treated will continue to grow. Clinicians must be aware of their potential for serious adverse side effects, including dermatitis, colitis, and potentially life-threatening pneumonitis.
The development of pneumonitis secondary to PD-1 inhibitions is reported to occur in 2% to 5% of patients and can present at any time during therapy, with 1% of patients developing grade 3 or higher pneumonitis.1,2 The most common symptoms are dyspnea and cough, though one-third of patients are asymptomatic at presentation.2 Radiographic and pathologic features vary greatly and include organizing pneumonia, interstitial pneumonitis, hypersensitivity pneumonitis, or diffuse alveolar damage.3 While pneumonitis due to PD-1 inhibition is reportedly uncommon, the increasing number of patients expected to receive these medications will predictably result in increasing overall frequency of pneumonitis cases. In addition, the lack of large prospective randomized trials and reliance on radiographic rather than pathologic data in diagnosing immune-mediated pneumonitis gives one pause. Given the variability of presentation, lack of routine pathologic data, and increasing use of dual agents (eg, PD-1 and CTLA-4), chest physicians and medical oncologists should have a high index of suspicion yet practice equipoise in patients receiving immunotherapy who develop unexplained pulmonary symptoms or infiltrates. More research is needed to help improve the multidisciplinary diagnosis and treatment of this potentially serious complication.
David Maurice Chambers, MD
Fellow-in-Training Member
Jason Atticus Akulian, MD, MPH
Steering Committee Member
References
1. Nishino M, et al. Incidence of programmed cell death 1 inhibitor-related pneumonitis in patients with advanced cancer: a systematic review and meta-analysis. JAMA Oncology. 2016;2(12):1607.
2. Naidoo J, et al. Pneumonitis in patients treated with anti-programmed death-1/programmed death ligand 1 therapy. J Clin Oncol. 2017;35(7):709.
3. Nishino M, et al. PD-1 inhibitor-related pneumonitis in advanced cancer patients: radiographic patterns and clinical course. Clin Cancer Res. 2016;22(24):6051.
Pulmonary Vascular Disease
Pulmonary Arterial Hypertension Associated With SLE
While pulmonary arterial hypertension (PAH) commonly complicates scleroderma (SSc), it is a rare complication of other connective tissue diseases (CTD), such as systemic lupus erythematosus (SLE). In the few prospective studies that utilize right-sided heart catheterization (RHC), the estimated prevalence of PAH in SLE is about 4%. However, since the prevalence of SLE is 10 to 15 times greater than SSc in the United States, the true prevalence of SLE-PAH may be higher than previously thought, and, thus, clinically relevant. Despite this, little is known about SLE-PAH.
A recent retrospective study from the French Pulmonary Hypertension Registry has added significantly to our understanding of this complication of SLE. Hachulla and colleagues studied 51 patients with RHC-proven SLE-PAH compared with 101 SLE control subjects without PAH. While the authors did not find any relevant differences in the demographics between groups, they did find a significantly higher prevalence of SSA and SSB antibodies in SLE-PAH. Interestingly, the presence of anti-U1 RNP antibody appeared to be less common in SLE-PAH patients; this lack of association is in contrast to prior studies in mixed CTD patients with anti-U1 RNP antibodies in which the prevalence of PAH can be as high as 60%. Further, none of the SLE-PAH patients demonstrated an acute response to vasodilator challenge during RHC, emphasizing that this maneuver does not need to be performed in SLE patients at risk of PAH. Trends toward improved survival in SLE-PAH patients treated with hydroxychloroquine are preliminary and hypothesis-generating but require confirmation in larger clinical studies.
Stephen Mathai, MD, FCCP
Chair
Leena Palwar, MD
Fellow-in-Training Member
Hachulla E, Jais X, Cinquetti G, et al. Pulmonary arterial hypertension associated with SLE: Results from the French pulmonary hypertension registry. Chest. 2017 Aug 26. pii: S0012-3692(17)31430-7. doi: 10.1016/j.chest.2017.08.014. [Epub ahead of print]
Chung L, Liu J, Parsons L, et al. Characterization of connective tissue disease-associated pulmonary arterial hypertension from REVEAL: identifying systemic sclerosis as a unique phenotype. Chest. 2010;138:1383-1394.
Shirai Y, Yasuoka H, Okano Y, Takeuchi T, Satoh T, Kuwana M. Clinical characteristics and survival of Japanese patients with connective tissue disease and pulmonary arterial hypertension: a singlecentre cohort. Rheumatology. 2012;51:1846-1854.
Hao YJ, Jiang X, Zhou W, et al. Connective tissue disease-associated pulmonary arterial hypertension in Chinese patients. Eur Respir J. 2014;44: 963-972.
Huang C, Li M, Liu Y, et al. Baseline characteristics and risk factors of pulmonary arterial hypertension in systemic lupus erythematosus patients. Medicine. 2016;95:e2761.
Pérez-Peñate GM, Rúa-Figueroa I, Juliá- Serdá G, et al. Pulmonary arterial hypertension in systemic lupus erythematosus: prevalence and predictors. J Rheumatol. 2016;43:323-329.
Alpert MA, Goldberg SH, Sindem BH, et al. Cardiovascular manifestations of mixed connective tissue disease in adults. Circulation. 1983;63:1182-1193.
Interventional Chest/Diagnostic Procedures
Cryobiopsy for ILD: Careful stewardship needed
Interest in transbronchial cryobiopsy has accelerated rapidly in recent years. This procedure is performed by advancing a cryoprobe into the peripheral lung via flexible bronchoscopy, where lung tissue freezes and adheres to the probe and is subsequently extracted as a cryobiopsy. The number of cryobiopsy-related publications has increased exponentially since it was described in 2009 (Babiak A, et al. Respiration. 2009;78[2]:203). This interest stems from reports of high diagnostic yields in patients with interstitial lung disease (ILD) while maintaining complication rates similar to that of conventional bronchoscopic biopsy.
Traditional bronchoscopic biopsies are notoriously insensitive; a specific diagnosis can be established in fewer than a third of cases (Sheth JS, et al. Chest. 2017;151[2]:389). As such, surgical lung biopsy continues to be recommended but is associated with significant mortality (2%) and morbidity (30%) in patients with ILD (Hutchinson JP, et al. ARJCCM. 2016;193[10]:1161). Cryobiopsy, which appears to rival surgical lung biopsy in terms of ability to contribute to a specific diagnosis, is, therefore, a highly promising alternative (Tomassetti S, et al. AJRCCM. 2016;193[7]:745).
As cryobiopsy is increasingly adopted around the world, however, troubling reports of serious complications have surfaced. Most notable is the recently reported experience of the initial 25 cases performed at the University of Pennsylvania, in which almost one in four patients suffered serious complications (DiBardino DM, et al. Ann Am Thorac Soc. 2017;14[6]:851). The authors pointed to lack of a predefined procedural protocol, as well as several choices relating to the specific technique used, including inconsistent use of fluoroscopy, lack of prophylactic bronchial blocker placement, and predominant use of laryngeal mask airways as potential contributing factors. Indeed, many variations of the basic cryobiopsy procedure have been described (Lentz RJ, et al. J Thoracic Dis. 2017;9[7]:2186), with no formal guidance or training available to inform advanced bronchoscopists interested in this procedure.
It is incumbent on the interventional pulmonology and ILD specialist communities to be responsible stewards of this promising procedure. Implementation of three parallel efforts to standardize and rigorously study this procedure should be considered as soon as possible: creation of expert consensus guidelines establishing best-practices for safe and effective biopsy technique; a training requirement before independent performance of the procedure; and creation of an international cryobiopsy registry to facilitate higher-quality research into optimal technique and outcomes. We owe this to our patients.
Robert J. Lentz, MD
NetWork Member
Fabien Maldonado, MD, FCCP
NetWork Member
Pediatric Chest Medicine
Chronic cough in children: New guidelines
A chronic cough is a common complaint among children whose parents seek medical evaluation. Chronic wet cough can indicate an underlying illness; therefore, an early diagnosis can lead to prevention of complications of the disease and improvement in quality of life.
CHEST is a leading resource in evidence and consensus-based guidelines on important topics affecting children. The most recent guidelines entitled Management of Children with Chronic Wet Cough and Protracted Bacterial Bronchitis (Chest. 2017;151(4):884-890) and Use of Management Pathways or Algorithms in Children with Chronic Cough (Chest. 2017;151(4):875-873) are updates from the 2006 CHEST guidelines on chronic cough in children.
The present updates utilized the CHEST methodological guidelines with chronic wet or productive cough and Grading of Recommendations Assessment, Development, and Evaluation framework and also performed a systematic review addressing key questions concerning the management of childhood disease for children 14 years and younger.
Guidance provided by the expert panel focused on recommendations to answer six key questions concerning the management of children 14 years and younger with a chronic wet cough unrelated to established chronic lung disease. The recommendations are:
1. Chronic cough is defined as the presence of a cough 4 weeks or longer in duration.
2. Assessment of the effect of the cough on the child and the family be undertaken as part of clinical consultation.
3. Evaluation of a chronic cough should be done with a systematic approach with pediatric-specific cough management protocols or algorithms.
4. Chest radiograph and, when age appropriate, spirometry with bronchodilator be undertaken as evaluation; tests for pertussis infection only to be performed if clinically suspected.
5. Chronic wet cough with no specific clinical features should receive antibiotics for 2 weeks targeted for common respiratory bacteria (Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis).
6. When cough persists despite 2 weeks of appropriate antibiotics, it is recommended to continue for an additional 2 weeks.
7. Additional tests (eg skin prick test, Mantoux, bronchoscopy, chest CT scan) should be individualized in accordance with the clinical setting and child’s clinical symptoms and signs.
The panel recognizes the need for prospective studies to assess current algorithms outcomes of children with chronic cough. Both articles can be found on the guidelines section of the CHEST site.
John Bishara, DO
Fellow-in-Training Member
Pulmonary Physiology, Function, and Rehabilitation
Functional imaging of the lung
Quantifying heterogeneity of ventilation and gas exchange in lung diseases remains a clinical challenge. Conventional pulmonary function test is insensitive to regional changes. The multiple inert gas elimination technique can quantify ventilation-perfusion distribution, but it requires invasive instrumentation (eg, pulmonary artery catheterization) and is not practical for clinical use. Computed tomography (CT) scans delineate spatial changes in lung structures but do not directly measure changes in ventilation and gas exchange. With its radiation, it is difficult to apply CT scanning repeatedly in patients. More recently, MR imaging techniques have been developed to directly “visualize” and quantify regional lung function (Kruger SJ, et al. J Magn Reson Imaging. 2016;43(2):295; Roos JE, et al. Magn Reson Imaging Clin N Am. 2015;23(2):217). These techniques employ inhalation of gases, such as oxygen, perfluorinated gases, and hyperpolarized 3He and 129Xe. Hyperpolarized 3He has been studied the most; however, the dwindling supply of 3He gas and its rising cost have prevented its further development. 129Xe has abundant supply and has emerged to be the inert gas of choice for MR imaging. Hyperpolarized 129Xe can measure ventilation, like hyperpolarized 3He. In addition, Xe diffuses into alveolar barrier (interstitium and plasma) and red blood cells, where it exhibits distinct resonant frequency shifts that can be captured by MR. Therefore, in one test, information on pulmonary ventilation and gas transfer can be obtained. To date, the results from MR imaging studies have provided new insights into the pathophysiology of obstructive and restrictive lung diseases. With continuous development, MR imaging of the lung could become a clinically useful tool in the near future.
Yuh-Chin T. Huang, MD, MHS, FCCP
Steering Committee Member
Thoracic Oncology
Immune-mediated pneumonitis and PD-1 inhibition
Inhibitors of the programmed cell death 1 receptor (PD-1) have shown significant promise in the treatment of advanced stage malignancy. With the recent expansion of indications for use of these agents, the number of patients treated will continue to grow. Clinicians must be aware of their potential for serious adverse side effects, including dermatitis, colitis, and potentially life-threatening pneumonitis.
The development of pneumonitis secondary to PD-1 inhibitions is reported to occur in 2% to 5% of patients and can present at any time during therapy, with 1% of patients developing grade 3 or higher pneumonitis.1,2 The most common symptoms are dyspnea and cough, though one-third of patients are asymptomatic at presentation.2 Radiographic and pathologic features vary greatly and include organizing pneumonia, interstitial pneumonitis, hypersensitivity pneumonitis, or diffuse alveolar damage.3 While pneumonitis due to PD-1 inhibition is reportedly uncommon, the increasing number of patients expected to receive these medications will predictably result in increasing overall frequency of pneumonitis cases. In addition, the lack of large prospective randomized trials and reliance on radiographic rather than pathologic data in diagnosing immune-mediated pneumonitis gives one pause. Given the variability of presentation, lack of routine pathologic data, and increasing use of dual agents (eg, PD-1 and CTLA-4), chest physicians and medical oncologists should have a high index of suspicion yet practice equipoise in patients receiving immunotherapy who develop unexplained pulmonary symptoms or infiltrates. More research is needed to help improve the multidisciplinary diagnosis and treatment of this potentially serious complication.
David Maurice Chambers, MD
Fellow-in-Training Member
Jason Atticus Akulian, MD, MPH
Steering Committee Member
References
1. Nishino M, et al. Incidence of programmed cell death 1 inhibitor-related pneumonitis in patients with advanced cancer: a systematic review and meta-analysis. JAMA Oncology. 2016;2(12):1607.
2. Naidoo J, et al. Pneumonitis in patients treated with anti-programmed death-1/programmed death ligand 1 therapy. J Clin Oncol. 2017;35(7):709.
3. Nishino M, et al. PD-1 inhibitor-related pneumonitis in advanced cancer patients: radiographic patterns and clinical course. Clin Cancer Res. 2016;22(24):6051.
Pulmonary Vascular Disease
Pulmonary Arterial Hypertension Associated With SLE
While pulmonary arterial hypertension (PAH) commonly complicates scleroderma (SSc), it is a rare complication of other connective tissue diseases (CTD), such as systemic lupus erythematosus (SLE). In the few prospective studies that utilize right-sided heart catheterization (RHC), the estimated prevalence of PAH in SLE is about 4%. However, since the prevalence of SLE is 10 to 15 times greater than SSc in the United States, the true prevalence of SLE-PAH may be higher than previously thought, and, thus, clinically relevant. Despite this, little is known about SLE-PAH.
A recent retrospective study from the French Pulmonary Hypertension Registry has added significantly to our understanding of this complication of SLE. Hachulla and colleagues studied 51 patients with RHC-proven SLE-PAH compared with 101 SLE control subjects without PAH. While the authors did not find any relevant differences in the demographics between groups, they did find a significantly higher prevalence of SSA and SSB antibodies in SLE-PAH. Interestingly, the presence of anti-U1 RNP antibody appeared to be less common in SLE-PAH patients; this lack of association is in contrast to prior studies in mixed CTD patients with anti-U1 RNP antibodies in which the prevalence of PAH can be as high as 60%. Further, none of the SLE-PAH patients demonstrated an acute response to vasodilator challenge during RHC, emphasizing that this maneuver does not need to be performed in SLE patients at risk of PAH. Trends toward improved survival in SLE-PAH patients treated with hydroxychloroquine are preliminary and hypothesis-generating but require confirmation in larger clinical studies.
Stephen Mathai, MD, FCCP
Chair
Leena Palwar, MD
Fellow-in-Training Member
Hachulla E, Jais X, Cinquetti G, et al. Pulmonary arterial hypertension associated with SLE: Results from the French pulmonary hypertension registry. Chest. 2017 Aug 26. pii: S0012-3692(17)31430-7. doi: 10.1016/j.chest.2017.08.014. [Epub ahead of print]
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