Acute Interstitial Pneumonia (Hamman-Rich Syndrome) in Lung Transplantation: A Case Series.

BACKGROUND: Acute interstitial pneumonia (AIP), also known as Hamman-Rich syndrome, is a rare and rapidly progressive idiopathic interstitial lung disease with a high mortality rate. Treatment is limited to supportive care and empirical high-dose steroids; however, outcomes are generally poor. There are few reports of lung transplantation (LTx) in patients with AIP. METHODS: We retrospectively identified patients with AIP among those who underwent LTx at our center between January 2008 and December 2020. RESULTS: During the study period, 4 patients with AIP underwent bilateral LTx: 3 men and 1 woman, between 30 and 57 years of age. The lung allocation score ranged between 71 and 89. Of the 4 patients, 2 needed extracorporeal membrane oxygenation and mechanical ventilation (MV) and 1 needed MV preoperatively. Time of onset to transplant ranged from 1 to 3 months. None of the patients had primary graft dysfunction after LTx; 2 had acute cellular rejection and 1 had chronic lung allograft dysfunction. The 4 patients are alive with survival ranging between 1 and 12 years after LTx. CONCLUSION: AIP should be considered in patients with acute respiratory failure without a clear etiology. Our study showed that LTx led to good outcomes and should be considered as a treatment option in appropriate candidates.

Outcomes of lung transplantation for idiopathic pleuroparenchymal fibroelastosis.

PURPOSE: This study was performed to compare the outcome of lung transplantation (LT) for idiopathic pleuroparenchymal fibroelastosis (IPPFE) with that of LT for idiopathic pulmonary fibrosis (IPF). METHODS: We reviewed, retrospectively, all adult patients who underwent LT for IPPFE or IPF in Japan between 1998 and 2018. RESULTS: There were 100 patients eligible for this study (31 with IPPFE and 69 with IPF). Patients with IPPFE tended to have a significantly lower body mass index (BMI) than those with IPF (median, 16.7 vs. 22.6 kg/m2, respectively; P < 0.01). However, Kaplan-Meier survival curves showed no significant difference in overall survival between the groups. The BMI did not increase in patients with IPPFE, even 1 year after LT (pretransplant, 16.5 ± 3.2 kg/m2 vs. 1 year post-transplant, 15.6 ± 2.5 kg/m2; P = 0.08). The percent predicted forced vital capacity (%FVC) 1 year after LT was significantly lower in the IPPFE group than in the IPF group (48.4% ± 19.5% vs. 68.6% ± 15.5%, respectively; P < 0.01). CONCLUSIONS: Despite extrapulmonary problems such as a flat chest, low BMI, and associated restrictive impairment persisting in patients with IPPFE, patient survival after LT for IPPFE or IPF was equivalent.

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.

Lung transplantation in IIP: A review.

The idiopathic interstitial pneumonias (IIP) encompass a large and diverse subtype of interstitial lung disease (ILD) with idiopathic pulmonary fibrosis (IPF) and non-specific interstitial pneumonia (NSIP) being the most common types. Although pharmacologic treatments are available for most types of IIP, many patients progress to advanced lung disease and require lung transplantation. Close monitoring with serial functional and radiographic tests for disease progression coupled with early referral for lung transplantation are of great importance in the management of patients with IIP. Both single and bilateral lung transplantation are acceptable procedures for IIP. Procedure selection is a complex decision influenced by multiple factors related to patient, donor and transplant centre. While single lung transplant may reduce waitlist time and mortality, the long-term outcomes after bilateral lung transplantation may be slightly superior. There are numerous complications following lung transplantation including primary graft dysfunction, chronic lung allograft dysfunction (CLAD), infections, gastroesophageal reflux disease (GERD) and airway disease that limit post-transplant longevity. The median survival after lung transplantation is 4.7 years in patients with ILD, which is less than in patients with other underlying lung diseases. Although long-term survival is limited, this intervention still conveys a survival benefit and improved quality of life in suitable IIP patients with advanced lung disease and chronic hypoxemic respiratory failure.

Expression of toll-like receptor 2 and 4 is increased in the respiratory epithelial cells of chronic idiopathic interstitial pneumonia patients.

BACKGROUND: Idiopathic interstitial pneumonia (IIP) is characterized by chronic interstitial inflammation and fibrosis. Although mounting evidence has suggested that toll-like receptor (TLR) 2 and TLR4 are involved in the pathogenesis of non-infectious lung injury in vitro and in mouse models, their roles in human IIP remain unknown. METHODS: To address this issue, we investigated the expression patterns of TLR2 and TLR4 by immunohistochemistry in resected lung tissues from patients with usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia (NSIP). RESULTS: Type II pneumocytes, bronchial epithelial cells (BECs), and alveolar macrophages accounted for the majority of TLR2- and TLR4-expressing cells in both UIP and NSIP. The numbers of TLR2 and TLR4-positive respiratory epithelial (RE) cells, including type II pneumocytes and BECs, were significantly greater in UIP and NSIP than in the control. In particular, the numbers of TLR2-positive RE cells were much greater in UIP than in NSIP. The intensities of TLR2 and TLR4 expression in type II pneumocytes were also significantly stronger in UIP and NSIP than in the control. A comparison of the TLR expression patterns between the fibroblastic and fibrotic areas in UIP indicated that the numbers TLR2 and TLR4-positive RE cells were similar in fibroblastic areas, whereas the TLR2-positive RE cells outnumbered the TLR4-positive RE cells in the fibrotic areas. CONCLUSIONS: This study demonstrates that RE cells over-express TLR2 and TLR4 in the lungs of IIP patients. These findings suggest that high expression of TLRs may contribute to the pathogenesis of human IIP.

Incidence and pattern of hemolytic anemia after minor ABO-mismatched living-donor lobar lung transplantation.

PURPOSE: Living-donor lobar lung transplantation (LDLLT) has been successfully performed in Japan. In LDLLT, the recipient usually receives one lower lobe from each of two donors; however, finding two ABO-matched donors is often difficult. Solid organ transplants from donors with minor ABO-mismatches can be complicated by hemolysis. We investigated the incidence of de novo anti-ABO antibody production and hemolysis in patients receiving LDLLT across minor ABO-mismatches. METHODS: We evaluated 23 patients who underwent LDLLT between June 2008 and December 2011, including 11 patients who underwent minor ABO-mismatched transplantation. We measured the anti-A/B antibody serum titers, hemoglobin concentrations and indirect bilirubin levels. RESULTS: None of the patients showed any clinical signs of hemolytic anemia (mean follow-up period; 16 months). Two of the 11 patients (18 %) receiving minor ABO-mismatched LDLLTs showed a small amount of de novo anti-B antibodies for a transient period. These patients showed gradual progression of anemia, and weak de novo anti-A/B antibodies were detected with column agglutination technology. The patients received only 2 U of washed type O red blood cells; thereafter, the hemolytic anemia did not develop further in either case. CONCLUSION: LDLLT across minor ABO-mismatches results in the transient appearance of weak de novo anti-A/B antibodies with a low incidence; thus, this procedure can be a safe treatment.

Histopathologic approach to the surgical lung biopsy in interstitial lung disease.

Interpretation of lung biopsy specimens is an integral part in the diagnosis of interstitial lung disease (ILD). The process of evaluating a surgical lung biopsy for disease involves answering several questions. Unlike much of surgical pathology of neoplastic lung disease, arriving at the correct diagnosis in nonneoplastic lung disease often requires correlation with clinical and radiologic findings. The topic of ILD or diffuse infiltrative lung disease covers several hundred entities. This article is meant to be a launching point in the clinician's approach to the histologic evaluation of lung disease.

[Complications of lung biopsy in patients with idiopathic interstitial pneumonia and risk factors thereof].

OBJECTIVES: To investigate the complication rate of lung biopsy in patients with idiopathic interstitial pneumonia (IIP) and the risk factors thereof. METHODS: The clinical data of 66 IIP patients underwent lung biopsy were analyzed. Of the 66 patients, 21 undergoing surgical lung biopsy (SLB) including open lung biopsy (OLB) (n = 11) and video-assisted thoracic surgery (VATS) (n = 10), and 45 patients undergoing biopsy other than SLB, including transbronchial lung biopsy (TBLB, n = 28) and CT or B mode ultrasonography-guided percutaneous transthoracic needle lung biopsy (n = 17). RESULTS: The general postoperative complication rate was 40.9% (27/66), and the postoperative complication rate was 71.4% (15/21) in the SLB group, significantly higher than that of the non-SLB group (26.7%, 12/45, chi2 = 4.55, P = 0.03). The complications of the SLB group included prolonged air leakage (n = 10, 47.6%), pleural effusion (n = 5, 23.8%), acute pulmonary edema (n = 5, 23.8%), and postoperative pulmonary infection (n = 4, 19.0%), and the complications of the non-SLB group included pneumothorax after percutaneous transthoracic lung needle biopsy or TBLB (n = 12, 26.7%), acute exacerbation (AE) (n = 2, 4.4%), respiratory failure requiring mechanical ventilation for more than 72 h (n = 1, 2.2%), and postoperative pulmonary infection (n = 1, 2.2%). The predicted diffusing capacity of the lings for carbon monoxide (DLCO%) of the SLB group patients with postoperative complications was (46. 83 +/- 17.01)%, significantly higher than that of the SLB group patients without postoperative complication [(75.93 +/- 25.62)%, t = 2.55, P = 0.02]. However, there were not significant differences in the lung function and blood gas indexes among the patients undergoing different procedures of lung biopsy, with and without postoperative complications. Six of the 66 patents died within 90 postoperative days with a mortality of 9.1%, the causes of death of 3 of which were associated with lung biopsy. CONCLUSIONS: The IIP patients undergoing SLB suffer from more postoperative complications than those undergoing other lung biopsy procedures with the lower DLCO% as the probable associated factor. AE in the IIP patients can be induced by CT-guided percutaneous transthoracic needle lung biopsy and TBLB, and results in death.

Recurrent lung cancer in the mediastinum noticed after a living-donor lobar lung transplantation.

We describe a case of lung cancer in a living-donor lobar lung transplantation (LDLLT) recipient that was identified because of a recurrence in the mediastinum. The patient was a 55-year-old woman who had undergone bilateral LDLLT for nonspecific interstitial pneumonia. She developed dyspnea upon exertion at 15 months after transplantation and was diagnosed as suffering from chronic rejection. A computed tomography scan also revealed enlarged mediastinal lymph nodes (LNs) that were subsequently confirmed as poorly differentiated squamous cell carcinomas. Retrospectively, a small tumor was found in the explanted right lung tissue, the microscopic findings of which were similar to those of the mediastinal lesion. A whole body examination revealed no other lesions; thus we resected the LNs and subsequently irradiated the mediastinum. Recurrent disease appeared in her transplanted lungs 10 months after resection of the LNs, and she died of pneumonia with chronic rejection 2 years and 7 months after transplantation.

Clinical course and lung function change of idiopathic nonspecific interstitial pneumonia.

Most studies of idiopathic nonspecific interstitial pneumonia (NSIP) have primarily studied mortality. In order to clarify the detailed outcome and prognostic markers in idiopathic NSIP, the clinical course with initial radiological and clinical features was analysed. The clinical course of 83 patients who were classified with idiopathic NSIP (72 fibrotic, 11 cellular; 27 males and 56 females; mean+/-sd age 54.4+/-10.1 yrs) was retrospectively analysed. In fibrotic NSIP, 16 (22%) patients died of NSIP-related causes with a median (range) follow-up of 53 (0.3-181) months. Despite the favourable survival (5-yr 74%), patients with fibrotic NSIP were frequently hospitalised with recurrence rate of 36%. Reduced forced vital capacity at 12 months was a predictor of mortality. On follow-up, lung function was improved or stable in approximately 80% of the patients. The extent of consolidation and ground-glass opacity on initial high-resolution computed tomography correlated significantly with serial changes of lung function, and the presence of honeycombing was a predictor of poor prognosis. During follow-up, eight (10%) patients developed collagen vascular disease. In conclusion, the overall prognosis of fibrotic nonspecific interstitial pneumonia was good; however, there were significant recurrences despite initial improvement and a subset of the patients did not respond to therapy. Some patients developed collagen vascular diseases at a later date.

Serum albumin concentration and waiting list mortality in idiopathic interstitial pneumonia.

BACKGROUND: Hypoalbuminemia is a reliable predictor of mortality in patients with various illnesses as well as a predictor of disability and mortality in healthy older adults. The association between hypoalbuminemia and mortality in patients with idiopathic interstitial pneumonia remains unknown. The objective of this study was to examine the relationship between serum albumin concentration and mortality in a large cohort of patients with idiopathic interstitial pneumonia listed for lung transplantation. METHODS: In patients classified as having idiopathic pulmonary fibrosis who were listed for lung transplantation with the United Network for Organ Sharing between January 1, 2004, and December 31, 2006 (n = 1,269), we studied the relationship between serum albumin concentration at the time of listing and mortality while awaiting transplantation. RESULTS: Lower serum albumin was associated with increased mortality rate. Patients with lower categories of serum albumin had increased mortality rates before and after multivariable adjustment (p value for linear trend < 0.0001). Analysis with serum albumin as a continuous predictor indicated that the mortality rate increased by 54% with each 0.5 g/dL decrease in serum albumin concentration (95% confidence interval, 32 to 79%). CONCLUSIONS: Lower serum albumin is strongly and independently associated with higher mortality in patients with idiopathic interstitial pneumonia on transplant waiting lists.