Idiopathic pleuroparenchymal fibroelastosis: consideration of a clinicopathological entity in a series of Japanese patients
© Kusagaya et al.; licensee BioMed Central Ltd. 2012
Received: 30 May 2012
Accepted: 29 November 2012
Published: 5 December 2012
Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is a recently reported group of disorders characterized by fibrotic thickening of the pleural and subpleural parenchyma predominantly in the upper lobes. We report five Japanese cases fulfilling the criteria of IPPFE and address whether it should be considered a separate clinicopathologic entity. And this study was an attempt to identify features in common between IPPFE and previously described idiopathic upper lobe fibrosis (IPUF), allowing IPPFE to be considered as a distinct entity in our Japanese series.
Five consecutive cases of idiopathic interstitial lung disease confirmed as IPPFE by surgical lung biopsy were studied.
There were four males and one female, aged 70±2.76 yr. No associated disorder or presumed cause was found in any case. Lung function tests found a restrictive ventilatory defect (4/5) and/or impairment of DLco (4/5). Chest X-ray showed marked apical pleural thickening in all cases. Computed tomography of the chest in all cases mainly showed intense pleural thickening and volume loss associated with evidence of fibrosis, predominantly in the upper lobes. In all cases in this study, markedly thickened visceral pleura and prominent subpleural fibrosis characterized by both elastic tissue and dense collagen were clearly shown. All cases were alive at the last follow-up, 17.6±13.59 months after diagnosis; however, all had deteriorated both clinically and radiologically.
IPPFE deserves to be defined as a separate, original clinicopathologic entity owing to its uniformity and IPPFE has some features in common with previously described idiopathic upper lobe fibrosis (IPUF). Our limited experience with a cohort of 5 subjects suggests that IPPFE can be rapidly progressive.
KeywordsIdiopathic interstitial lung disease Pleural fibrosis Fibroelastosis Pleuroparenchymal fibroelastosis
Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is a recently reported rare disorder characterized by fibrotic thickening of the pleural and subpleural parenchyma predominantly in the upper lobes ; as such IPPFE is distinct from other types of idiopathic interstitial pneumonia . Since 1992 several reports of upper lobe-predominant pulmonary fibrosis (Idiopathic upper lobe fibrosis/IPUF) have been reported in the Japanese literature [3–9] and some of these cases share features with IPPFE. Herein we report five Japanese cases of IPPFE, and describe the clinical, radiologic and evolutionary profile of IPPFE in a retrospective series in order to determine if IPPFE represents a separate clinicopathologic entity and to clarify its relationship with IPUF.
The subjects included 5 patients fulfilling criteria IPPFE diagnosed by surgical lung biopsy  (SLB) from May 2009 to Sep 2011 at Hamamatsu University Hospital and affiliated hospitals in Japan. Lung biopsies were performed by video-assisted thoracoscopy, and specimens were obtained from 2 or more lobes in every case. We used the pathological criteria for the diagnosis of IPPFE as follows: (1) intense fibrosis of the visceral pleura; (2) prominent, homogenous, subpleural fibroelastosis; (3) sparing of the parenchyma distant from the pleura; (4) mild, patchy lymphoplasmocytic infiltrates; and (5) small numbers of fibroblastic foci present. All of our reported cases met all of the criteria. This criteria is based on the paper by Frankel et al. . Surgical lung specimens were also reviewed by an expert pulmonary pathologist (T.V.C.). This study was approved by the Institutional Review Board of Hamamatsu University School of Medicine. Clinical data were obtained from case medical records. Laboratory findings and pulmonary function test results at the time of SLB were also recorded.
Clinical features and biology
Clinical characteristics and laboratory data
BAL lym (%)
Survive 12 months
Survive 6 months
Survive 44 months
Survive 10 months
Survive 16 months
Pulmonary function test
Pulmonary function test data
TLC (L), %predicted (%)
FVC (L), %predicted (%)
FEV1 (L), %predicted (%)
FRC (L), %predicted (%)
RV (L), %predicted (%)
RV/TLC (%), %predicted (%)
DLco (mL/min/mmHg), %predicted (%)
DLco/VA (mL/min/mmHg), %predicted (%)
Treatment and clinical outcome
It is clear that IPPFE is not a new pulmonary disease. As Reddy et al  reported, it has previously received other names, such as idiopathic upper lobe fibrosis (IPUF), and has more frequently been described in the Japanese literature [3–5, 9] and may be more common in the Japanese. IPPFE has been defined as a distinct entity in the English literature by Frankel et al.; a unique clinical presentation and precise characteristic pathologic criteria are described . Our study was an attempt to identify features in common between these two entities, allowing IPPFE to be considered distinct as it applies to our Japanese series.
The clinical presentation and the findings of the lung function tests were characteristic of restrictive interstitial lung disease. Radiological features were also characteristic, including intense pleural thickening associated with evidence of fibrosis, most striking pattern in the upper lobes with volume loss and architectural distortion. The upper lobes were always more severely involved, with involvement of the lower lobes being absent or less marked. Piciucchi and colleagues reported that one case had honeycombing on HRCT findings in their cases . In our series, no patients had honeycombing. In all the reports describing PPFE, eight out of total 25 cases (32%) had a history of malignancy. Among those cases, four cases had treatment with BMT  and those cases presented with histological evidence of obliterative bronchiolitis, which was not a feature in those with idiopathic presentation of PPFE, suggesting that bone marrow transplantation is a potential etiology at least in a subgroup of cases with pleuroparenchymal fibroelastosis. In our series, Case 1 had a history of gingival cancer treated with surgery followed by adjuvant chemotherapy. However, no cases had BMT, and other cases never had malignancy.
In terms of therapy and prognosis, previous cases of IPPFE showed a 40% mortality rate. In addition, many cases gradually deteriorated. In our series, consistent with previous reports, although no death occurred, all the cases clinically and functionally deteriorated even in a relatively short follow-up period. There are no therapeutic options available for IPPFE except for supportive care and ultimately lung transplantation. Regarding the mechanism of elastosis, it has not been determined whether fibroelastosis occurred by overproduction of elastin or impairment of degradation. Pirfenidone is an antifibrotic drug, currently used only for idiopathic pulmonary fibrosis (IPF) [13–15], which inhibits fibrotic factors, most notably TGFβ. As a consequence, downstream synthesis of extracellular matrix proteins, such as fibronectin, elastin and collagen, is reduced [16, 17]. Hence, it may potentially be beneficial for cases of IPPFE.
There are several case reports of idiopathic, upper lobe-predominant fibrosis in the Japanese language literature [3–6, 9]. Among those reports, it has been described that the thinness of the body was a characteristic of the disease. Consistent with these reports, our cases showed low BMI. However, there are no data on BMI or body weight of patients with IPPFE in reports from outside of Japan. Radiologically upper lobe predominance is associated with both IPUF and IPPFE. As both IPUF and IPPFE are relatively rare and only recently described, there are no guidelines or criteria as to how extensive the opacities in the middle and lower lobes can be. In terms of other aspects of the disease, such as possible occurrence of pneumothorax, infection and slow progression of the disease, IPPFE and IPUF seem to be within the same spectrum of disease. Although IPUF patients with surgical lung biopsy or autopsy were reported in some Japanese literature, there are no pathological criterias as IPUF. But in all those cases, intraalveolar fibrosis and subpleural elastosis were noted. Those findings are same to the pathological findings with IPPFE. Interestingly, the specimens from some patients shows UIP like pattern in the lower lobe. Amitani et al.  strictly defined the lesion is in the upper lobe, but the report from Shiota et al.  include the patients with UIP like lesion. Reddy  also mentioned patients with PPFE had the fibrosis in the lower lobe. Further studies are needed what is the possible lesion in mid-lower lobe. Finally, pulmonary surfactant protein D (SP-D) was elevated in all cases in our series. It is expressed in alveolar type II and bronchiolar epithelial cells and is secreted into alveoli and conducting airways [18, 19]. Our data suggest that those epithelial cells may play a role in the fibrotic process of the diseases.
There are some limitations to the present study. First, there were selection and recall biases because this was a retrospective study. Since the current authors’ institutions are regional referral centers for diffuse lung disease, the proportion and severity of the disease reported here may differ substantially from those found in the community. Second, the sample size was too small to determine the precise prevalence and clinical characteristics of IPPFE. Prospective studies incorporating larger series are necessary to verify these results.
This study shows that the clinical, radiological and pathological presentation of IPPFE is remarkably uniform in cases with apparently idiopathic lung disease. We thus consider that idiopathic PPFE deserves to be defined as a distinct clinicopathological syndrome largely overlapping with previously described IPUF. It should be distinguished from other types of interstitial lung disease, especially because it is highly progressive.
Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
body mass index
sialylated carbohydrate antigen KL-6
surfactant protein D
total lung capacity
forced vital capacity
forced expiratory volume
functional residual capacity
diffusing capacity for carbon monoxide
diffusing capacity divided by the alveolar volume.
We thank Dr. Takeshi Johkoh (Kinki Central Hospital of Mutual Aid Association of Public School Teachers, Itami City, Japan) for helpful comments. This study was partly supported by a grant to the Diffuse Lung Diseases Research Group from the Ministry of Health, Labour and Welfare, Japan.
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- The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2466/12/72/prepub