Single-lung transplantation for pulmonary alveolar microlithiasis: A case report.

BACKGROUND: Pulmonary alveolar microlithiasis (PAM) is a rare idiopathic lung disease characterized by the accumulation of innumerable microliths. Currently, effective therapeutics for PAM are not available, and the only treatment for end-stage lung disease is lung transplantation (LuTx). Further, there are few reports that focus on LuTx for the treatment of PAM, and the follow-up reports of postoperative imaging are even rarer. CASE
SUMMARY: A 52-year-old man presented to Shanghai Pulmonary Hospital in 2017 after experiencing shortness of breath and exacerbation. The patient was diagnosed with PAM and referred for single-LuTx (SLuTx) on March 14, 2018. Preoperative imaging results from a chest X-ray demonstrated bilateral, diffuse, symmetrical, sandstorm-like radiopaque micronodules, and pneumothorax and a computed tomography scan revealed minute, calcified military nodules in both lungs. We performed a left SLuTx, and intraoperative pathology was consistent with PAM. One week after surgery, a chest X-ray revealed slight exudation of the left lung, and one month later, the left transplanted lung exhibited good dilation, mild pulmonary perfusion injury with local infection, and left pleural effusion. Fiberoptic bronchoscopy revealed left hyperplastic granulation at the left bronchial anastomosis. Multiple sputum cultures suggested the presence of Klebsiella pneumoniae and Acinetobacter baumannii. The last follow-up was conducted in April 2019; the patient recovered well.
CONCLUSION: This case presents the imaging findings of a patient with PAM before and after LuTx and confirms the effectiveness of LuTx for the treatment of this disease. ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.

Core tip: Pulmonary alveolar microlithiasis (PAM) is a rare idiopathic lung disease characterized by the accumulation of innumerable microliths. Currently, there are no effective therapeutic drugs for PAM, and the only treatment for end-stage lung disease is lung transplantation (LuTx). Here we present a rare case of alveolar microlithiasis transplantation. This case highlights the importance of imaging findings of PAM before and after LuTx and confirms the effectiveness of LuTx for the treatment of PAM.

INTRODUCTION

Pulmonary alveolar microlithiasis (PAM) is a rare idiopathic lung disease characterized by the accumulation of innumerable microliths that consist primarily of calcium and phosphorus in pulmonary alveoli[1]. PAM was first described by an Italian scientist in 1868, and more than 1000 cases have been reported worldwide[2]. Currently, there is no medical therapy available to alter the progression of PAM definitively, and lung transplantation (LuTx) is usually performed when patients are diagnosed with end-stage lung disease[3]. Here, we report a successful case of left single-LuTx (SLuTx) in a patient with PAM for the first time in China.

CASE PRESENTATION

Chief complaints

A 52-year-old man (weight, 55 kg; height, 172 cm) was referred for a LuTx after experiencing shortness of breath with chest tightness for 4 years and exacerbation for 10 d.

History of present illness

The patient coughed and expectorated since childhood and experienced chest tightness and shortness of breath that gradually increased after exercise since 2014. He was diagnosed with PAM by using fiberoptic bronchoscopy at Shanghai Pulmonary Hospital in 2017. The patient had three instances of pneumothorax in the left lung over a period of 6 months and received poor treatment. On March 14, 2018, the patient was evaluated for LuTx at Wuxi People’s Hospital.

History of past illness

The patient’s past medical history was unremarkable.

Personal and family history

The patient’s brother experienced similar symptoms, although he had not been diagnosed at a hospital.

Physical examination

Both lungs had low respiratory sounds and slightly moist rales.

Laboratory examinations

The results of liver and heart function tests were as follows: Albumin, 34.5 g/L (normal range: 35.0-53.0 g/L); lactic dehydrogenase, 246.0 U/L (normal range: 109.0-245.0 U/L); and globulin, 35.8 g/L (normal range: 17.0-33.5 g/L). Immunological parameters were as follows: Immunoglobulin A, 5.7 g/L (normal range: 0.7-5.0 g/L); immunoglobulin M, 3.03 g/L (normal range: 0.4-2.8 g/L); and complement C3, 786.0 mg/L (normal range: 790.0-1520.0). Tumor indices were as follows: CA125: 249.5 U/mL (normal range: < 35.0 U/mL) and C-reactive protein, 17.3 mg/L (normal range: 0-8.0 mg/L).

Imaging examinations

A preoperative chest X-ray demonstrated bilateral, diffuse, symmetrical, sandstorm-like radiopaque micronodules and pneumothorax, and a chest computed tomography (CT) scan revealed decreased diffuse transmittance and calcified minute miliary nodules in both lungs (Figure 1A-C). The clinical symptoms and imaging results were consistent PAM. After discussion and approval by the hospital ethics committee, the patient was placed on the waiting list for LuTx.

Figure 1

Preoperative imaging results suggestive of pulmonary alveolar microlithiasis. A: Chest X-ray image showing bilateral, diffuse, symmetrical, sandstorm-like radiopaque micronodules and pneumothorax; B: Chest computed tomography (CT; pulmonary window) image showing decreased diffuse transmittance; C: Chest CT (mediastinal window) image showing calcified, minute miliary nodules in both lungs.

FINAL DIAGNOSIS

Intraoperative pathology revealed the accumulation of calcium salts in the alveoli (Figure 2). A final diagnosis of PAM was established.

Figure 2

Intraoperative pathology showing large amounts of calcium salts in the alveoli (magnification, ×100).

TREATMENT

On April 9, 2018, the lung from a 28-year-old donor (weight, 70 kg; height, 175 cm) became available for our patient. The donor was in good health and pronounced brain dead following intracerebral hemorrhage. The donor’s close relatives agreed to donate his organs. The patient’s and donor’s ABO and Rh blood groups were the same, their body type and chest circumference matched, and panel reactive antibody and human leukocyte antigen were negative. The donor’s lung was cut off according to the standard protocol, preserved with raffinose-low potassium dextran solution, and transported.

We performed a left SLuTx with extracorporeal membrane oxygenation (ECMO). During this procedure, few adhesions were noted in the left side of the chest. We observed diffuse consolidation of the left lung, and it had a firm, sandy texture. Intraoperative blood loss was 1600 mL, and transfusion of 1600 mL of blood was performed. The cooling time for the supply lung was 7.5 h.

After the operation, the patient was transferred to the intensive care unit (ICU). Postoperative intubation time was 3 d, and ECMO was removed 2 d later due to hypoxia. After 5 d, he was transferred from the ICU to the general ward for further treatment.

OUTCOME AND FOLLOW-UP

One week after surgery, a chest X-ray showed slight exudation of the left lung (Figure 3A), and one month later, the left transplanted lung showed good dilation, mild pulmonary perfusion injury with local infection (Figure 3B), and left pleural effusion (Figure 3C). Fiberoptic bronchoscopy revealed obstruction of the left bronchial anastomosis caused by hyperplastic granulation and the accumulation of yellow and white sticky moss. Multiple sputum cultures suggested the presence of Klebsiella pneumoniae and Acinetobacter baumanii. The patient was discharged from the hospital in a stable condition after treatment. In September, anastomotic stenosis was improved after bronchoscopic balloon dilatations were performed three times (Figure 3D). The last follow-up was conducted in April 2019, and the patient recovered well (Figure 4).

Figure 3

Postoperative imaging. A: Postoperative chest radiograph (1 wk after surgery) revealing slight exudation in the left lung; B: High-resolution computed tomography (CT) image showing good dilation of the left transplanted lung, with mild pulmonary perfusion injury and local infection; C: CT image showing left-sided pleural effusion; D: CT image showing a left-sided main bronchial stricture.

Figure 4

Postoperative imaging. A and B: Chest computed tomography images acquired at the last follow-up visit in April 2019 indicate a good recovery.

DISCUSSION

PAM is an autosomal recessive disease caused by mutations in the SLC34A2 gene, which lead to defects in the sodium phosphate-IIb cotransporter protein. These defects prevent the clearance of phosphate and calcium phosphate deposits from the extracellular fluid by alveolar type II epithelial cells[4]. PAM has a familial genetic tendency, and familial cases account for about 30%-50% of all cases. Additionally, there is a slight predominance among males[5]. Previous studies (Table 1) reported that five patients mentioned their family history in the literature, one of whom had a family history, and our patient stated that his brother had similar symptoms but had not been diagnosed in hospital.

Table 1

Summary of case reports related to lung transplantation in patients with pulmonary alveolar microlithiasis

Ref.	Yr	Age	Family history	Double/Single LuTx	Complications	Outcome
Bonnette et al[14]	1992	46	NR	Double	No	Alive, NR
Stamatis et al[11]	1993	32	YES	Double	Major bleeding	Alive, 18 m
Raffa et al[15]	1996	48	NO	Single	Acute rejection, anastomotic stenosis	Alive, 12 m
Edelman et al[16]	1997	56	NO	Double	Major bleeding	Dead, POD 5
		35	NR		No	Alive, 32 m
Jackson et al[12]	2001	53	NR	Single	No	Alive, 90 m
Coulibaly et al[17]	2009	43	NR	Double	Infection	Dead, 3 m
Shadmehr et al[18]	2009	32	NR	Single	Hemodynamically instable, reperfusion edema	Dead, NR
Shigemura et al[19]	2010	63	NR	Double	No	Alive, 16 m
Samano et al[20]	2010	47	NO	Double	Reperfusion syndrome, shock	Alive, 12 m
Borrelli et al[21]	2014	64	NR	Single	NR	Alive, 60 m
Güçyetmez et al[22]	2014	52	NR	Double	NR	Alive, 12 m
Klikovits et al[9]	2016	32	NR	Double	PGD, Sepsis	Dead, 11 d
		52			Reperfusion-edema	Alive, 74 d
		34			No	Alive, 67 d
		52			No	Alive, 35 d
		52			Atrial fibrillation	Alive, 29 d
Delic et al[23]	2016	73	NO	Double	NR	Alive, NR

NR: Not reported; PGD: Primary graft dysfunction; POD: Postoperative day.

Some patients may be asymptomatic initially; however, as the disease progresses, both lungs become fibrotic, which may lead to restrictive ventilatory disorder and respiratory failure[6]. Our patient coughed and expectorated since childhood, experienced shortness of breath for four years prior to his diagnosis, and gradually received medical treatment. The patient’s symptoms were consistent with the clinical manifestations of PAM.

The typical picture of PAM on a chest X-ray is sand-like, calcific micronodules that diffusely infiltrating both lungs, especially the middle and lower zones, and this is called “sandstorm lung”. The increased calcific density in lower zones is due to the larger surface area and greater thickness. While PAM is progressing, extensive microliths may cause obscuration of the mediastinal and diaphragmatic silhouette. Additionally, bullous emphysema may also be observed at the anterior margin or apex. Moreover, chest CT scans show thickening of the lobular septae with a distribution of microliths along the septae and around the centrilobular distal bronchioles. This is called “crazy paving” pattern[1,3,7]. Our patient had high-density micronodules in both lungs and repeated unhealed left pneumothorax, which were consistent with typical imaging manifestations.

Although the use of disphosphonates has been promoted for the treatment of PAM, there are mixed results associated with this treatment[3]. Currently, LuTx is an effective treatment for patients with end-stage PAM. However, owing to the small number of cases and lack of prognostic factors around the world, there are currently no guidelines for LuTx timing[8]. Based on our experience, LuTx is needed to be considered when respiratory failure, pneumothorax, or acute exacerbations occur and the patient requires long-term oxygen therapy. Table 1 summarizes the information from existing case reports of PAM. The mean age of 18 patients with PAM was 48.1 ± 11.9 years, which is similar to the age of the patient in the current study. Further, only four patients (Table 1) received SLuTx, for which the patient’s condition and lung imaging findings needed to be considered. Previous studies have reported that bilateral lung replacements are more effective than SLuTx because unilateral replacements may lead to shunting of blood through the underventilated native lung[9]. However, other studies have demonstrated that patients who received SLuTx had no evidence of recurrence in the transplanted lung[10,11,12]; therefore, a study that implements a longer follow-up period after SLuTX in patients with PAM should be conducted. Because our patient had acute pulmonary edema and acute left heart failure during the operation, and the left pneumothorax was unhealed before the surgery, the surgeon chose single LuTx finally. Further, recurrence was not observed during the first year after the operation.

Complications after LuTx are the main cause of death of patients undergoing transplantation. Infections are the second (18.7%) and main (36.3%) causes of death, respectively, from 30 days to 1 year after operation[13]. From the cases that we reviewed, two patients died from infections at 11 days (sepsis, n = 1/18) and 3 mo (n = 1/18) after operation, respectively. Other postoperative complications, including anastomotic stenosis, acute rejection, and reperfusion edema, occurred in 14 survival cases (Table 1). Some complications are associated with different imaging features. For example, infections are characterized by diffuse ground glass opacities, localized atelectasis or consolidation, small intrapulmonary nodules, peri-bronchovascular interstitial thickening, and pleural effusions. Acute rejection is characterized by diffuse ground glass opacities, consolidation, septal thickening, and pleural effusions. Bronchial stenosis refers to a narrowing of the bronchus in the CT. Based on these imaging features, our patient was diagnosed with local infection and stenosis.

CONCLUSION

The patient in this study was preoperatively diagnosed with PAM based on fiberoptic bronchoscopy biopsy, and imaging findings, such as the “sandstorm lung” from chest X-ray scans and the “crazy paving” pattern from chest CT scans, supported the diagnosis. In addition, our results demonstrated that LuTx is an effective treatment for patients with end-stage PAM. Further, the prevention of postoperative complications is important in order to improve the prognosis of patients who have received transplantations.

ACKNOWLEDGEMENTS

I would like to express gratitude to my colleagues who provided me with references and information on time.