CONTENTS
- Basics
- Epidemiology
- Clinical presentation
- Radiology
- Differential diagnosis
- Diagnostic approach
- Management
- Prognosis
- Questions & discussion
abbreviations used in the pulmonary section: 1
- ABPA: Allergic bronchopulmonary aspergillosis 📖
- AE-ILD: Acute exacerbation of ILD 📖
- AEP: Acute eosinophilic pneumonia 📖
- AFB: Acid Fast Bacillus
- AIP: Acute interstitial pneumonia (Hamman-Rich syndrome) 📖
- ANA: Antinuclear antibody 📖
- ANCA: Antineutrophil cytoplasmic antibodies 📖
- ARDS: Acute respiratory distress syndrome 📖
- ASS: Antisynthetase Syndrome 📖
- BAL: Bronchoalveolar lavage 📖
- BiPAP: Bilevel positive airway pressure 📖
- CEP: Chronic eosinophilic pneumonia 📖
- COP: Cryptogenic organizing pneumonia 📖
- CPAP: Continuous positive airway pressure 📖
- CPFE: Combined pulmonary fibrosis and emphysema 📖
- CTD-ILD: Connective tissue disease associated interstitial lung disease 📖
- CTEPH: Chronic thromboembolic pulmonary hypertension 📖
- DAD: Diffuse alveolar damage 📖
- DAH: Diffuse alveolar hemorrhage 📖
- DIP: Desquamative interstitial pneumonia 📖
- DLCO: Diffusing capacity for carbon monoxide 📖
- DRESS: Drug reaction with eosinophilia and systemic symptoms 📖
- EGPA: Eosinophilic granulomatosis with polyangiitis 📖
- FEV1: Forced expiratory volume in 1 second 📖
- FVC: Forced vital capacity 📖
- GGO: Ground glass opacity 📖
- GLILD: Granulomatous and lymphocytic interstitial lung disease 📖
- HFNC: High flow nasal cannula 📖
- HP: Hypersensitivity pneumonitis 📖
- IPAF: Interstitial pneumonia with autoimmune features 📖
- IPF: Idiopathic pulmonary fibrosis 📖
- IVIG: Intravenous immunoglobulin 📖
- LAM: Lymphangioleiomyomatosis 📖
- LIP: Lymphocytic interstitial pneumonia 📖
- MAC: Mycobacterium Avium complex 📖
- MCTD: Mixed connective tissue disease 📖
- NIV: Noninvasive ventilation (including CPAP or BiPAP) 📖
- NSIP: Nonspecific interstitial pneumonia 📖
- NTM: Non-tuberculous mycobacteria 📖
- OP: Organizing pneumonia 📖
- PAP: Pulmonary alveolar proteinosis 📖
- PE: Pulmonary embolism 📖
- PFT: Pulmonary function test 📖
- PLCH: Pulmonary Langerhans Cell Histiocytosis 📖
- PPFE: Pleuroparenchymal fibroelastosis 📖
- PPF: Progressive pulmonary fibrosis 📖
- PVOD/PCH Pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis 📖
- RB-ILD: Respiratory bronchiolitis-associated interstitial lung disease 📖
- RP-ILD: Rapidly progressive interstitial lung disease 📖
- TNF: tumor necrosis factor
- UIP: Usual Interstitial Pneumonia 📖
- Pleuroparenchymal fibroelastosis is a fibrotic lung disease centered on the lung apices. It shares numerous similarities with IPF (idiopathic pulmonary fibrosis).
- PPFE may occur either alone, or in combination with a variety of fibrosing interstitial lung diseases (e.g., idiopathic pulmonary fibrosis, connective tissue disease-associated ILD, and fibrosing hypersensitivity pneumonitis). (35855575)
most cases are idiopathic
- PPFE usually presents between ~40-70 years old, but the there is a wide age range. (Fishman 2023, 34366047; 31425665)
- There is no link to smoking. (35855575)
- A family history of pulmonary fibrosis is often found, in some cases related to mutations that cause short telomeres. (32654735, 35680316) Further discussion of short telomere syndromes here: 📖
- PPFE may occur in combination with IPF (idiopathic pulmonary fibrosis). Among patients with IPF, ~10% may have PPFE as well. (35855575)
PPFE may be secondary/associated with:
- Lung transplant rejection (as a radiographic manifestation of restrictive chronic allograft dysfunction 📖). The incidence of PPFE may be on the order of 7%. (31425665)
- Hematopoietic stem cell transplantation:
- PPFE may be seen along with bronchiolitis obliterans syndrome (BOS), possibly as a manifestation of chronic GVHD (graft versus host disease).
- PPFE occurs years after transplantation.
- The absolute risk of developing PPFE seems to be low (<1%). (31425665)
- Medications & radiation therapy: (Pneumotox.com: 🌊)
- Alkylating chemotherapy agents (e.g., carmustine, cyclophosphamide).
- Dapsone.
- Daptomycin.
- Statins (including simvastatin).
- Rheumatologic disorders:
- Scleroderma.
- Rheumatoid arthritis.
- Sjogren syndrome.
- Inflammatory bowel disease.
- Fibrosing HP (hypersensitivity pneumonitis).
- Dust exposure:
- Aluminum.
- Asbestos.
- Silica. (Walker 2019; 35855575)
symptoms
- The most common symptoms are a triad:
- (1) Progressive exertional dyspnea is the primary symptom.
- (2) Dry cough may occur.
- (3) Severe weight loss is common. (31916971)
- Pleuritic or nonspecific chest pain may occur. (35855575)
- Spontaneous pneumothorax:
- PPFE is progressive in most patients. Eventually chronic hypercapnic respiratory failure may develop. (35855575)
physical examination
- Platythorax: (~50%)
- This refers to flattening of the chest (with reduced anteroposterior diameter). Platythorax may result from a combination of upper lobe contraction and weight loss. (32654735)
- An unusually deep suprasternal notch may be noted on examination (figure below). (Fishman 2023)
- Digital clubbing occurs in ~15-20% (especially if there is a combination of PPFE plus idiopathic pulmonary fibrosis). (35855575)
- Lung auscultation is generally normal (unless there is another coexisting lung disease).(31425665)
chest radiograph
- Bilateral apical, irregular pleural thickening may be seen.
- Upper lobe volume loss may cause the hila to be pulled upwards.
CT scan
- Apices are notable for:
- Pleural thickening, with dense subpleural consolidation.
- Traction bronchiectasis.
- There is clear demarcation between fibrotic lung and unaffected lung.
- In advanced disease, honeycombing and bullae may occur (which explains the tendency to develop pneumothorax).
- Shifts in thoracic geometry:
- Hila are retracted upwards (due to upper lobe volume loss).
- Trachea may be deviated rightwards. (32654735) The trachea may also overlap with the spine in the anterior-posterior dimension, due to flattening of the chest wall.
- Comparison to prior CT scans may reveal progressive flattening of the chest wall over time, as the disease progresses. (32654735)
- Coexisting lower lobe interstitial changes are increasingly reported:
- Pathological studies indicate that PPFE rarely extends into the lung base. Therefore, any fibrosis in the lung base is likely due to an additional process (e.g., IPF, NSIP, or hypersensitivity pneumonitis). (35855575)
- IPF (idiopathic pulmonary fibrosis) is the most frequent coexisting interstitial lung disease. (Fishman 2023)
- See the list of diseases involving the upper lung zones: 📖
- The closest differential diagnoses may often be:
- Organizing pneumonia.
- CEP (chronic eosinophilic pneumonia).
- Hypersensitivity pneumonitis.
- Sarcoidosis.
- Nontuberculous mycobacterial infection.
- Pneumoconiosis.
tissue biopsy is discouraged
- Transbronchial or transthoracic needle biopsy has a low yield and a high risk of pneumothorax. (31916971)
- Surgical lung biopsy may provide a more secure diagnosis. However, this carries a high risk of serious adverse events (including pneumothorax with prolonged air leak, or acute exacerbation of interstitial lung disease).
Enomoto et al. criteria for noninvasive PPFE diagnosis:
- (1) Bilateral apical subpleural dense consolidation with or without pleural thickening in the upper lobes, and less marked or absent involvement of the lower lobes.
- (2) Radiological confirmation of disease progression, defined as one of the following:
- Increase in the upper lobe consolidation with or without pleural thickening.
- Decrease in upper lobe volume on serial radiological assessment.
- (3) Exclusion of other lung diseases with identifiable causes (e.g., connective tissue disease-related ILD, chronic hypersensitivity pneumonitis, sarcoidosis, pneumoconiosis, and active pulmonary infection). (29173442)
treatment should probably be similar to IPF (idiopathic pulmonary fibrosis)
- PPFE is extremely rare, so high-quality data regarding this is not available.
- Overall, this process seems to be similar to IPF. It may be reasonable to borrow a therapeutic strategy from the IPF literature.
immunosuppressive therapy
- Immunosuppressive therapy doesn't appear to be effective and is generally discouraged. (Murray 2022; 35855575)
- Similar to IPF, PPFE seems to be a primarily fibrotic disorder (unlike many other interstitial lung diseases, in which inflammation eventually leads to secondary fibrosis).
antifibrotic therapy
- Early initiation of antifibrotic therapy is a rational therapy.
- Nintedanib was found to slow disease progression in a small retrospective study. (34627338)
- Pirfenidone has been used for patients with PPFE following lung transplantation. (Fishman 2023)
supportive care (overall similar to the treatment of IPF)
- Lung transplantation should often be considered. When in doubt, serial follow-up with imaging and pulmonary function tests may help determine disease trajectory and avoid delayed referral for transplantation.
- Oxygen supplementation may be indicated.
- Noninvasive ventilation may be helpful for patients with daytime hypercapnia. (35855575)
- Pulmonary rehabilitation.
- Nutritional support (patients have a tendency to lose weight).
- Vaccination (there may be a predisposition towards pneumonia). (32654735)
- Disease course is variable:
- Some patients may steadily decline.
- Some patients may have periods of stability, followed by an accelerated decline.
- Poor prognostic factors may include:
- Reduced FVC (forced vital capacity).
- Deteriorating FVC over time.
- Decreased BMI (body mass index).
- Simultaneous involvement of the lower lobes with UIP (usual interstitial pneumonia).
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References
- 31425665 Chua F, Desai SR, Nicholson AG, Devaraj A, Renzoni E, Rice A, Wells AU. Pleuroparenchymal Fibroelastosis. A Review of Clinical, Radiological, and Pathological Characteristics. Ann Am Thorac Soc. 2019 Nov;16(11):1351-1359. doi: 10.1513/AnnalsATS.201902-181CME [PubMed]
- 31916971 Kwon M, Mira-Avendano I, Khoor A, Mallea J. A 64-Year-Old Man With Rapidly Progressive Respiratory Failure and Pneumomediastinum. Chest. 2020 Jan;157(1):e5-e8. doi: 10.1016/j.chest.2019.07.026 [PubMed]
- 32654735 Dimeas IE, Sinis SI, Sgantzou IK, Ioannou M, Gourgoulianis KI, Daniil Z. Chronic Progressive Dyspnea in a 71-Year-Old Man: A Diagnostic Ithaca After 8 Years of Consultation. Chest. 2020 Jul;158(1):e25-e31. doi: 10.1016/j.chest.2020.02.003 [PubMed]
- 34366047 Homer KL, Mandziuk J, Hirji A, Barrie J, Meyer SR, Wong EYL, Puttagunta L, Halloran KM. Progressive Dyspnea With Recurrent Pneumothoraces. Chest. 2021 Aug;160(2):e209-e215. doi: 10.1016/j.chest.2021.03.052 [PubMed]
- 35680316 Baptista M, Barata J, Craveiro AP, Guimarães S, Valente MJ. A 30-Year-Old Man With Cough, Dyspnea, and Upper Lobe Opacities. Chest. 2022 Jun;161(6):e359-e363. doi: 10.1016/j.chest.2021.12.671 [PubMed]
- 35855575 Cottin V, Si-Mohamed S, Diesler R, Bonniaud P, Valenzuela C. Pleuroparenchymal fibroelastosis. Curr Opin Pulm Med. 2022 Sep 1;28(5):432-440. doi: 10.1097/MCP.0000000000000907 [PubMed]
Books:
- Shah, P. L., Herth, F. J., Lee, G., & Criner, G. J. (2018). Essentials of Clinical pulmonology. In CRC Press eBooks. https://doi.org/10.1201/9781315113807
- Shepard, JO. (2019). Thoracic Imaging The Requisites (Requisites in Radiology) (3rd ed.). Elsevier.
- Walker C & Chung JH (2019). Muller’s Imaging of the Chest: Expert Radiology Series. Elsevier.
- Palange, P., & Rohde, G. (2019). ERS Handbook of Respiratory Medicine. European Respiratory Society.
- Rosado-De-Christenson, M. L., Facr, M. L. R. M., & Martínez-Jiménez, S. (2021). Diagnostic imaging: chest. Elsevier.
- Murray & Nadel: Broaddus, V. C., Ernst, J. D., MD, King, T. E., Jr, Lazarus, S. C., Sarmiento, K. F., Schnapp, L. M., Stapleton, R. D., & Gotway, M. B. (2021). Murray & Nadel’s Textbook of Respiratory Medicine, 2-Volume set. Elsevier.
- Fishman's: Grippi, M., Antin-Ozerkis, D. E., Cruz, C. D. S., Kotloff, R., Kotton, C. N., & Pack, A. (2023). Fishman’s Pulmonary Diseases and Disorders, Sixth Edition (6th ed.). McGraw Hill / Medical.
