A CARE-compliant case report: Lung transplantation for a Chinese young man with idiopathic pleuroparenchymal fibroelastosis.

RATIONAL: Pleuroparenchymal fibroelastosis (PPFE) is a rare interstitial lung disease that is characterized radiologically by apical pleural thickening and histologically by elastic fibrosis of the visceral pleura. Although PPFE cases have been reported occasionally since this disease was initially described, most such cases have involved secondary PPFE. Idiopathic PPFE (iPPFE) cases have been less thoroughly studied. There are no effective medications for patients with iPPFE. PATIENT CONCERNS: A 34-year-old man with no asbestos or cigarette exposure was admitted to our ward due to worsening cough and exertional dyspnea for 10 years. He had a "flattened thoracic cage" and bibasilar inspiratory crackles without finger clubbing. A series of chest computed tomography scans during the preceding 10 years revealed the presence of gradual, exaggerated, upper lung-predominant, diffuse pleural thickening and dense subpleural opacification with traction bronchiectasis. DIAGNOSIS: He was performed with video-assisted thoracic surgical (VATS) lung biopsy. The pulmonary histopathologic examination showed thickened visceral pleura and prominent subpleural fibroelastosis, confirming the diagnosis of iPPFE. INTERVENTION: After the failure of treatment with prednisone plus cyclophosphamide and sequential pirfenidone administration, he was arranged with bilateral lung transplantation two years later. OUTCOMES: The patient did not require supplemental oxygenation anymore after he recovered from lung transplantation. LESSONS: Bilateral lung transplantation might be tried for the end-stage iPPFE cases.

Introduction

Idiopathic pleuroparenchymal fibroelastosis (iPPFE) is a rare subtype of idiopathic interstitial pneumonia.[ There is no effective treatment for primary or secondary PPFE.[ We report successful bilateral lung transplantation in a 36-year-old male with iPPFE after the failure of treatment with prednisone plus cyclophosphamide and sequential pirfenidone administration. Written informed consent for the case report was obtained from this patient, and the consent procedure was approved by the Ethics Committee of the Peking Union Medical College Hospital.

Case report

A 34-year-old man with no asbestos or cigarette exposure was admitted to our ward due to worsening cough and exertional dyspnea for 10 years. He had continually been healthy before 2003. The patient had a “flattened thoracic cage” and bibasilar inspiratory crackles without finger clubbing. A series of chest computed tomography scans during the preceding 10 years revealed the presence of gradual, exaggerated, upper lung-predominant, diffuse pleural thickening, and dense subpleural opacification with traction bronchiectasis (Fig. 1A–D). Assessments of antinuclear antibody, antiextractable nuclear antigen, antineutrophil cytoplasmic antibodies, human leukocyte antigen-B27, and rheumatoid factor all produced negative results. A pulmonary function test in November 2013 revealed restrictive ventilatory dysfunction and impaired diffusion, with the following specific findings: forced vital capacity (FVC), 1.3 L/41.2% of predicted; the ratio of forced expiratory volume in 1 second (FEV1) to FVC (FEV1/FVC), 84.7%; total lung capacity (TLC), 2.31 L/33.1% of predicted; and diffusion capacity of carbon monoxide (DLco), 4.12 mmol/min/kPa/36.5% of predicted. In December 2013, a video-assisted thoracic surgical (VATS) lung biopsy revealed thickened visceral pleura and prominent subpleural fibroelastosis (Fig. 2A, B), confirming the diagnosis of iPPFE. Prednisone at an initial dosage of 1 mg/kg/d and cyclophosphamide (2 mg/kg/d) were prescribed beginning in January 2014. Prednisone was tapered after 2 weeks. Because the patient's clinical condition had not improved after 8 months of treatment, prednisone and cyclophosphamide were discontinued. Subsequently, the patient was consulted regarding lung transplantation and was placed on a transplantation list. He was administered 1800 mg/d pirfenidone for approximately 6 months starting in February 2015. However, his respiratory condition gradually deteriorated, and his pulse oxygenation at rest was less than 90%. In May 2016, bilateral lung transplantation was successfully performed. After the patient recovered from transplantation, he did not require supplemental oxygenation. PPFE was pathologically confirmed based on his extracted lung.

Figure 1

The axial and coronal high-resolution computed tomography (HRCT) images demonstrating upper lung-predominant diffuse pleural thickening and subpleural dense opacification with traction bronchiectasis (A–D).

Figure 2

Surgical lung biopsy specimens showed thickened visceral pleura and prominent subpleural fibroelastosis which was positive with elastic fiber staining significantly. There was clear borderline between the thickened pleura and the normal underlying lung tissue (A: HE stain, ×40; B: elastic fiber staining, ×100).

Discussion

Pleuroparenchymal fibroelastosis is a rare interstitial lung disease that was initially defined as pulmonary upper lobe fibrosis.[ PPFE is characterized radiologically by apical pleural thickening and histologically by elastic fibrosis of the visceral pleura.[ In 2013, iPPFE was defined to be a subtype of rare idiopathic interstitial pneumonia.[ Studies about PPFE have occasionally been published, and more than 100 PPFE cases have been reported.[ Most of these cases involved PPFE secondary to organ or stem cell transplantation, chemotherapy, autoimmune disease, or recurrent infection.[ iPPFE cases have been less thoroughly studied.

Among reported PPFE cases, there is no sex preponderance or a slight female predominance. A report indicated that the ages of PPFE patients range from 13 to 87 years, with a mean of 53 years.[ It appears that age of onset is related to the underlying disease.[ Smoking is not significantly associated with PPFE. The most common clinical manifestations of PPFE are a dry cough, exertional dyspnea, weight loss, and recurrent pneumothorax.[ In most PPFE cases, crackles are common, but finger clubbing is rare. In contrast to iPPFE cases reported by Kusagaya et al, which involved patients older than 60 years, with a mean age of 70 years, our patient was a 34-year-old male nonsmoker. He was slender and presented with a flattened thoracic cage, which appears to be a characteristic physical feature in PPFE cases.[ Reports have indicated that this flattened cage might relate to shrinkage of the upper lung lobes via the prolonged fibrotic process.

Although chest imaging is important, pathological manifestations are vital for determining a final diagnosis of PPFE.[ Typical idiopathic PPFE is defined pathologically as involving intense fibrosis of the visceral pleura; prominent homogeneous subpleural fibroelastosis; sparing of the parenchyma distant from the pleura; mild, patchy lymphoplasmacytic infiltrates; and the presence of small numbers of fibroblastic foci.[ In our case, pathological findings from the VATS lung biopsy and the posttransplantation extracted lungs were consistent with diagnostic criteria for iPPFE.

To date, no recommended treatment options are available for iPPFE. However, corticosteroids and/or immunosuppressive agents have been prescribed for most cases of this disease.[ Oxygenation and infection control may be necessary for progressive cases. Pirfenidone is a new antifibrotic drug that can inhibit fibrotic factors, particularly TGF-β, and reduce the deposition of extracellular matrix proteins, including fibronectin, elastin, and collagen.[ Watanabe et al[ prescribed pirfenidone for PPFE cases, but this treatment was not efficacious. We administered pirfenidone in our case after the failure of prednisone and cyclophosphamide, but the patient's respiratory condition deteriorated. Lung transplantation has been reported for 2 cases of end-stage secondary PPFE.[ Our case might constitute the first reported example of an iPPFE patient who underwent bilateral lung transplantation.

There were some limitations of our report. First, he took pirfenidone only for approximately 6 months before the transplantation. Second, it was just about 6 months after the bilateral lung transplantation, and he should be followed up longer.

Conclusions

Idiopathic PPFE is rare and there are no effective medications for the patients with iPPFE. Bilateral lung transplantation might be tried for the end-stage iPPFE cases.