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A 64-Year-Old Man With Rapidly Progressive Respiratory Failure and Pneumomediastinum
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CHEST Pearls
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A 64-Year-Old Man With Rapidly Progressive Respiratory Failure and Pneumomediastinum Minkyung Kwon, MD; Isabel Mira-Avendano, MD; Andras Khoor, MD; and Jorge Mallea, MD
A 64-year-old man presented for consideration for lung transplant. He had a history of previous tobacco use, OSA on CPAP therapy, and gastroesophageal reflux disease. He worked as a design engineer. The patient had a 4-year history of dyspnea on exertion, followed with periodic CT scan of the chest. Nine months prior to his evaluation for lung transplant, the patient developed worsening of dyspnea, dry cough, poor appetite, and weight loss. At times, the cough was violent and associated with chest pressure. He was prescribed systemic corticosteroids and antibiotics without improvement. Four months later, the patient noted sudden onset of severe chest pain and worsening dyspnea. A CT scan of the chest demonstrated extensive pneumomediastinum in addition to changes consistent with pulmonary fibrosis. An esophagogram showed thickening of the distal esophagus, but no signs of perforation. He was prescribed supplemental oxygen and advised to stop the use of CPAP. The patient sought a second opinion. A CT scan of the chest showed improvement of the pneumomediastinum and extensive fibrotic lung disease. Pulmonary function tests (PFTs) were consistent with a restrictive pattern, decreased diffusing capacity (DLCO), and a preserved residual volume over total lung capacity ratio. The patient was prescribed systemic corticosteroids with no improvement of his symptoms. Repeat PFTs showed further decline of DLCO, and he was referred for lung transplant evaluation.
CASE PRESENTATION:
CHEST 2020; 157(1):e5-e8
Physical Examination Findings The patient was afebrile and his BP was 128/78 mm Hg, with a pulse rate of 106 beats/min and oxygen saturation on pulse oximetry of 93% on 2 L/min oxygen applied by nasal cannula. His BMI was 19 kg/m2. He was thin and illlooking. The chest examination showed decrease excursion, diffuse crackles, and normal heart sounds. There was no clubbing. There was a stage 1 sacral decubitus ulcer. The rest of the physical examination was normal.
Diagnostic Studies
32.6 mm Hg, and PaO2 of 43.5 mm Hg on room air. Serum creatinine level was 0.9 mg/dL. Rheumatologic serologies were negative. Pulmonary function test (PFT) revealed restrictive pattern (total lung capacity of 48% predicted, FVC of 50% predicted, and decreased diffusing capacity (DLCO) of 34% predicted). CT scan revealed pneumomediastinum and pneumothoraces in the background of pleuroparenchymal thickening (Figs 1A-C).
Blood hemoglobin level, leukocyte count, and platelet count were normal. Arterial blood gas measurements showed a pH of 7.49, PaCO2 of AFFILIATIONS: From the Division of Pulmonary, Allergy and Sleep Medicine (Drs Kwon, Mira-Avendano, and Mallea), Department of Laboratory Medicine & Pathology (Dr Khoor), and Division of Transplant Medicine (Dr Mallea), Mayo Clinic, Jacksonville, FL. CORRESPONDENCE TO: Jorge Mallea, MD, Division of Pulmonary, Allergy and Sleep Medicine, Division of Transplant Medicine, Mayo
chestjournal.org
Clinic, 4500 San Pablo Rd, Jacksonville, FL 32224; e-mail: Mallea. [email protected] Copyright Ó 2019 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved. DOI: https://doi.org/10.1016/j.chest.2019.07.026
e5
Figure 1 – A-C, Chest CT scan of the patient over time. A, Chest CT scan 9 months prior to evaluation showing prominent upper lobe subpleural thickening and bronchiectasis. B, Chest CT scan at the time of pneumomediastinum and pneumothorax. C, Chest CT scan at the time of lung transplant evaluation. Progression of fibrosis and honeycombing also involving the lower lobes.
What is the diagnosis?
e6 CHEST Pearls
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157#1 CHEST JANUARY 2020
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Diagnosis: Idiopathic pleuroparenchymal fibroelastosis Discussion Idiopathic pleuroparenchymal fibroelastosis (PPFE) is a rare idiopathic interstitial pneumonia characterized by upper lobe predominant pleural and subpleural lung parenchymal fibrosis, which clinically leads to progressive respiratory failure. Beyond its rarity, the exact incidence or prevalence is not known. It can occur at any age or in either sex, regardless of exposure to cigarette smoking. It has been described in patients with history of bone marrow transplant, lung transplant, chemotherapy, and occupational dust exposure, but no clear causative factor has been determined. Familial cases have been reported, suggesting genetic predisposition. Patients present with chronic dyspnea and cough. Patients experience severe weight loss similar to cachexia in malignancy. On physical examination, bilateral crackles are auscultated. Cyanosis and clubbing are not uniformly seen. PFTs show a restrictive pattern, decreased DLCO, and an elevated residual volume over total lung capacity (RV/TLC) ratio. Arterial blood gas is characterized by hypoxia and hypercapnia, with a normal alveolar-arterial gradient. No autoantibodies are detected in the serum, and BAL fluid shows no characteristic cell differentiation. Radiographic features are characteristic enough to raise strong suspicion of the diagnosis. On plain chest radiograph, lung volume loss and hilar elevation are seen. CT scan of the chest findings include marked bilateral apical pleural thickening with honeycombing and traction bronchiectasis in the upper lobes. Some patients with PPFE show lower lobe subpleural
reticulation and honeycomb changes, indistinguishable from the usual interstitial pneumonia pattern, suggesting a possible overlap between PPFE and idiopathic pulmonary fibrosis in these cases. Confirmatory diagnosis of PPFE can only be made by histopathology using elastic stains, which reveal pleural and subpleural parenchymal elastotic fibrosis. There is a characteristic abrupt transition from fibroelastosis to normal lung parenchyma. Partial stenosis of the pulmonary vasculature, both arterial and venous, can often be seen. However, elastotic fibrosis is not specific to PPFE; it can also be seen in apical cap and pulmonary infarction. Therefore, histopathologic changes can only be interpreted in the context of consistent physiological and chest CT scan findings. Surgical lung biopsy is preferred for the diagnosis. However, it may lead to serious adverse events, including pneumothorax with prolonged air leak and bronchopleural fistula. Transbronchial or transthoracic needle biopsy can be attempted, but the diagnostic yield is lower and the risk of pneumothorax remains high with these procedures. Differential diagnoses of PPFE include apical cap, advanced fibrosing sarcoidosis, and chronic hypersensitivity pneumonitis. Apical caps cannot be separated from PPFE on histopathologic grounds alone; chest CT scan correlation is necessary. Advanced fibrosing sarcoidosis and chronic hypersensitivity pneumonitis are in the differential diagnosis because of their upper lobe predominance. These entities are not commonly associated with pneumothoraces and do not show the elastotic fibrosis characteristic of PPFE on histopathologic examination. The prognosis of PPFE is poor; the 5-year survival is 29%. The causes of death are progressive hypercarbic
Figure 2 – A-B, Lung autopsy examination. Stains reveal upper lobe-predominant elastotic fibrosis of the pleura and subpleural pulmonary parenchyma, with abrupt transition to normal lung, consistent with pleuroparenchymal fibroelastosis. A, Hematoxylin and eosin stain (original magnification 15). B, Verhoeff-van Gieson elastic stain (original magnification 15).
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2. PPFE may be idiopathic or related to bone marrow transplant, lung transplant, chemotherapy, and occupational exposure. 3. The development of spontaneous pneumomediastinum or pneumothorax in a patient with upper lobe predominant pleuroparenchymal disease suggests the diagnosis. 4. PFTs show a restrictive pattern, impaired DLCO, and an elevated RV/TLC ratio. Figure 3 – Higher magnification of lung autopsy. Hematoxylin and eosin stain focally reveals acute lung injury, with hyaline membranes and type II pneumocyte hyperplasia (original magnification 400).
respiratory failure and pneumothorax. Most patients exhibit steady progression, but a long asymptomatic phase followed by accelerated decline has been observed. There is no effective treatment except for lung transplant. Clinical Course
Bilateral upper lobe pleuroparenchymal disease on CT scan, restrictive PFT pattern, spontaneous pneumothorax, and pneumomediastinum raised the suspicion of PPFE. The patient required admission to the ICU and mechanical ventilation because his respiratory condition continued to deteriorate. The patient was deemed not a suitable candidate for lung transplant because of severe malnutrition and deconditioning. Hospice care was requested by the patient’s family, and the patient died shortly after discontinuation of mechanical ventilation. Autopsy confirmed the diagnosis of PPFE (Fig 2) with acute lung injury (Fig 3).
Clinical Pearls 1. PPFE presents with progressive dyspnea and cough.
e8 CHEST Pearls
5. PPFE differs from idiopathic pulmonary fibrosis in its compromise of the upper lobes and pleural involvement, and histologic features (elastotic fibrosis). 6. Surgical lung biopsy carries the risk of persistent bronchopleural fistula. 7. Once recognized, patients with PPFE should be referred to lung transplant evaluation.
Acknowledgments Financial/nonfinancial disclosures: None declared. Other contributions: CHEST worked with the authors to ensure that the Journal policies on patient consent to report information were met.
Suggested Readings Frankel SK, Cool CD, Lynch DA, Brown KK. pleuroparenchymal fibroelastosis - description of clinicopathologic entity. Chest. 2004;126(6):2007-2013.
Idiopathic a novel
Reddy TL, Tominaga M, Hansell DM, et al. Pleuroparenchymal fibroelastosis: a spectrum of histopathological and imaging phenotypes. Eur Respir J. 2012;40(2):377-385. Travis WD, Costabel U, Hansell DM, et al. An official American Thoracic Society/European Respiratory Society statement: update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med. 2013;188(6):733-748. Enomoto Y, Nakamura Y, Satake Y, et al. Clinical diagnosis of idiopathic pleuroparenchymal fibroelastosis: a retrospective multicenter study. Respir Med. 2017;133:1-5. Khiroya R, Macaluso C, Montero MA, et al. Pleuroparenchymal fibroelastosis: a review of histopathologic features and the relationship between histologic parameters and survival. Am J Surg Pathol. 2017;41(12):1683-1689.
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157#1 CHEST JANUARY 2020
]
CHEST Pearls
]
A 64-Year-Old Man With Rapidly Progressive Respiratory Failure and Pneumomediastinum Minkyung Kwon, MD; Isabel Mira-Avendano, MD; Andras Khoor, MD; and Jorge Mallea, MD
A 64-year-old man presented for consideration for lung transplant. He had a history of previous tobacco use, OSA on CPAP therapy, and gastroesophageal reflux disease. He worked as a design engineer. The patient had a 4-year history of dyspnea on exertion, followed with periodic CT scan of the chest. Nine months prior to his evaluation for lung transplant, the patient developed worsening of dyspnea, dry cough, poor appetite, and weight loss. At times, the cough was violent and associated with chest pressure. He was prescribed systemic corticosteroids and antibiotics without improvement. Four months later, the patient noted sudden onset of severe chest pain and worsening dyspnea. A CT scan of the chest demonstrated extensive pneumomediastinum in addition to changes consistent with pulmonary fibrosis. An esophagogram showed thickening of the distal esophagus, but no signs of perforation. He was prescribed supplemental oxygen and advised to stop the use of CPAP. The patient sought a second opinion. A CT scan of the chest showed improvement of the pneumomediastinum and extensive fibrotic lung disease. Pulmonary function tests (PFTs) were consistent with a restrictive pattern, decreased diffusing capacity (DLCO), and a preserved residual volume over total lung capacity ratio. The patient was prescribed systemic corticosteroids with no improvement of his symptoms. Repeat PFTs showed further decline of DLCO, and he was referred for lung transplant evaluation.
CASE PRESENTATION:
CHEST 2020; 157(1):e5-e8
Physical Examination Findings The patient was afebrile and his BP was 128/78 mm Hg, with a pulse rate of 106 beats/min and oxygen saturation on pulse oximetry of 93% on 2 L/min oxygen applied by nasal cannula. His BMI was 19 kg/m2. He was thin and illlooking. The chest examination showed decrease excursion, diffuse crackles, and normal heart sounds. There was no clubbing. There was a stage 1 sacral decubitus ulcer. The rest of the physical examination was normal.
Diagnostic Studies
32.6 mm Hg, and PaO2 of 43.5 mm Hg on room air. Serum creatinine level was 0.9 mg/dL. Rheumatologic serologies were negative. Pulmonary function test (PFT) revealed restrictive pattern (total lung capacity of 48% predicted, FVC of 50% predicted, and decreased diffusing capacity (DLCO) of 34% predicted). CT scan revealed pneumomediastinum and pneumothoraces in the background of pleuroparenchymal thickening (Figs 1A-C).
Blood hemoglobin level, leukocyte count, and platelet count were normal. Arterial blood gas measurements showed a pH of 7.49, PaCO2 of AFFILIATIONS: From the Division of Pulmonary, Allergy and Sleep Medicine (Drs Kwon, Mira-Avendano, and Mallea), Department of Laboratory Medicine & Pathology (Dr Khoor), and Division of Transplant Medicine (Dr Mallea), Mayo Clinic, Jacksonville, FL. CORRESPONDENCE TO: Jorge Mallea, MD, Division of Pulmonary, Allergy and Sleep Medicine, Division of Transplant Medicine, Mayo
chestjournal.org
Clinic, 4500 San Pablo Rd, Jacksonville, FL 32224; e-mail: Mallea. [email protected] Copyright Ó 2019 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved. DOI: https://doi.org/10.1016/j.chest.2019.07.026
e5
Figure 1 – A-C, Chest CT scan of the patient over time. A, Chest CT scan 9 months prior to evaluation showing prominent upper lobe subpleural thickening and bronchiectasis. B, Chest CT scan at the time of pneumomediastinum and pneumothorax. C, Chest CT scan at the time of lung transplant evaluation. Progression of fibrosis and honeycombing also involving the lower lobes.
What is the diagnosis?
e6 CHEST Pearls
[
157#1 CHEST JANUARY 2020
]
Diagnosis: Idiopathic pleuroparenchymal fibroelastosis Discussion Idiopathic pleuroparenchymal fibroelastosis (PPFE) is a rare idiopathic interstitial pneumonia characterized by upper lobe predominant pleural and subpleural lung parenchymal fibrosis, which clinically leads to progressive respiratory failure. Beyond its rarity, the exact incidence or prevalence is not known. It can occur at any age or in either sex, regardless of exposure to cigarette smoking. It has been described in patients with history of bone marrow transplant, lung transplant, chemotherapy, and occupational dust exposure, but no clear causative factor has been determined. Familial cases have been reported, suggesting genetic predisposition. Patients present with chronic dyspnea and cough. Patients experience severe weight loss similar to cachexia in malignancy. On physical examination, bilateral crackles are auscultated. Cyanosis and clubbing are not uniformly seen. PFTs show a restrictive pattern, decreased DLCO, and an elevated residual volume over total lung capacity (RV/TLC) ratio. Arterial blood gas is characterized by hypoxia and hypercapnia, with a normal alveolar-arterial gradient. No autoantibodies are detected in the serum, and BAL fluid shows no characteristic cell differentiation. Radiographic features are characteristic enough to raise strong suspicion of the diagnosis. On plain chest radiograph, lung volume loss and hilar elevation are seen. CT scan of the chest findings include marked bilateral apical pleural thickening with honeycombing and traction bronchiectasis in the upper lobes. Some patients with PPFE show lower lobe subpleural
reticulation and honeycomb changes, indistinguishable from the usual interstitial pneumonia pattern, suggesting a possible overlap between PPFE and idiopathic pulmonary fibrosis in these cases. Confirmatory diagnosis of PPFE can only be made by histopathology using elastic stains, which reveal pleural and subpleural parenchymal elastotic fibrosis. There is a characteristic abrupt transition from fibroelastosis to normal lung parenchyma. Partial stenosis of the pulmonary vasculature, both arterial and venous, can often be seen. However, elastotic fibrosis is not specific to PPFE; it can also be seen in apical cap and pulmonary infarction. Therefore, histopathologic changes can only be interpreted in the context of consistent physiological and chest CT scan findings. Surgical lung biopsy is preferred for the diagnosis. However, it may lead to serious adverse events, including pneumothorax with prolonged air leak and bronchopleural fistula. Transbronchial or transthoracic needle biopsy can be attempted, but the diagnostic yield is lower and the risk of pneumothorax remains high with these procedures. Differential diagnoses of PPFE include apical cap, advanced fibrosing sarcoidosis, and chronic hypersensitivity pneumonitis. Apical caps cannot be separated from PPFE on histopathologic grounds alone; chest CT scan correlation is necessary. Advanced fibrosing sarcoidosis and chronic hypersensitivity pneumonitis are in the differential diagnosis because of their upper lobe predominance. These entities are not commonly associated with pneumothoraces and do not show the elastotic fibrosis characteristic of PPFE on histopathologic examination. The prognosis of PPFE is poor; the 5-year survival is 29%. The causes of death are progressive hypercarbic
Figure 2 – A-B, Lung autopsy examination. Stains reveal upper lobe-predominant elastotic fibrosis of the pleura and subpleural pulmonary parenchyma, with abrupt transition to normal lung, consistent with pleuroparenchymal fibroelastosis. A, Hematoxylin and eosin stain (original magnification 15). B, Verhoeff-van Gieson elastic stain (original magnification 15).
chestjournal.org
e7
2. PPFE may be idiopathic or related to bone marrow transplant, lung transplant, chemotherapy, and occupational exposure. 3. The development of spontaneous pneumomediastinum or pneumothorax in a patient with upper lobe predominant pleuroparenchymal disease suggests the diagnosis. 4. PFTs show a restrictive pattern, impaired DLCO, and an elevated RV/TLC ratio. Figure 3 – Higher magnification of lung autopsy. Hematoxylin and eosin stain focally reveals acute lung injury, with hyaline membranes and type II pneumocyte hyperplasia (original magnification 400).
respiratory failure and pneumothorax. Most patients exhibit steady progression, but a long asymptomatic phase followed by accelerated decline has been observed. There is no effective treatment except for lung transplant. Clinical Course
Bilateral upper lobe pleuroparenchymal disease on CT scan, restrictive PFT pattern, spontaneous pneumothorax, and pneumomediastinum raised the suspicion of PPFE. The patient required admission to the ICU and mechanical ventilation because his respiratory condition continued to deteriorate. The patient was deemed not a suitable candidate for lung transplant because of severe malnutrition and deconditioning. Hospice care was requested by the patient’s family, and the patient died shortly after discontinuation of mechanical ventilation. Autopsy confirmed the diagnosis of PPFE (Fig 2) with acute lung injury (Fig 3).
Clinical Pearls 1. PPFE presents with progressive dyspnea and cough.
e8 CHEST Pearls
5. PPFE differs from idiopathic pulmonary fibrosis in its compromise of the upper lobes and pleural involvement, and histologic features (elastotic fibrosis). 6. Surgical lung biopsy carries the risk of persistent bronchopleural fistula. 7. Once recognized, patients with PPFE should be referred to lung transplant evaluation.
Acknowledgments Financial/nonfinancial disclosures: None declared. Other contributions: CHEST worked with the authors to ensure that the Journal policies on patient consent to report information were met.
Suggested Readings Frankel SK, Cool CD, Lynch DA, Brown KK. pleuroparenchymal fibroelastosis - description of clinicopathologic entity. Chest. 2004;126(6):2007-2013.
Idiopathic a novel
Reddy TL, Tominaga M, Hansell DM, et al. Pleuroparenchymal fibroelastosis: a spectrum of histopathological and imaging phenotypes. Eur Respir J. 2012;40(2):377-385. Travis WD, Costabel U, Hansell DM, et al. An official American Thoracic Society/European Respiratory Society statement: update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med. 2013;188(6):733-748. Enomoto Y, Nakamura Y, Satake Y, et al. Clinical diagnosis of idiopathic pleuroparenchymal fibroelastosis: a retrospective multicenter study. Respir Med. 2017;133:1-5. Khiroya R, Macaluso C, Montero MA, et al. Pleuroparenchymal fibroelastosis: a review of histopathologic features and the relationship between histologic parameters and survival. Am J Surg Pathol. 2017;41(12):1683-1689.
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157#1 CHEST JANUARY 2020
]