Literature DB >> 31670307

An "Orphan" in search of a treatment: Pulmonary alveolar microlithiasis.

Manjit Sharad Tendolkar1.   

Abstract

Entities:  

Year:  2019        PMID: 31670307      PMCID: PMC6852224          DOI: 10.4103/lungindia.lungindia_437_19

Source DB:  PubMed          Journal:  Lung India        ISSN: 0970-2113


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From the first macroscopic description of this disease by Malpighi[1] in 1868, and the first case report by Harbitz[2] in 1918 to coining of the term “pulmonary alveolar microlithiasis (PAM)” by Puhr[3] in 1933, we have succeeded in uncovering the pathophysiology and the genetic basis of the disease. The medical treatment, however, continues to elude us. PAM is a rare and a chronic disease characterized by the presence of extensive interalveolar calculi or microliths, spherical calcium and phosphate deposits, forming concentric lamellae surrounding an amorphous central nucleus measuring up to 2 μm.[4] The association of PAM with an autosomal recessive mutation of SLC34A2 gene which encodes for sodium phosphate cotransporter is well documented. This is the only phosphate transporter expressed in Type II pneumocytes. Degradation of surfactant produces phosphate which eventually accumulates to form microliths which characterize this disease. The hallmark of this disease is the clinico-radiological dissociation. This disease is often detected incidentally on the radiograph as the calcified lesions in the lung fields are difficult to be missed by the physician while the patient has minimal symptoms. More than 50% of the cases are asymptomatic. However, when symptomatic cough and breathlessness are the primary complaints, the former likely attributable to stimulation of unmyelinated c fibers in bronchial tree by microliths.[5] This disease is rare. Less than 100 cases have been reported from India in the literature, whereas the world literature has <1100 such cases. There is no definitive treatment for PAM. Given the minimal discomfort of the patient, physicians tend to manage this conservatively. In cases wherein the patient is symptomatic, there have been trials showing conflicting results by disodium etidronate in PAM. Although not approved by the Food and Drug Administration for PAM, it is one of the few drugs to be considered in our armamentarium against PAM. It acts by inhibiting formation of new pulmonary calcium phosphate crystallization and resolving previously formed calcifications. Apart from disodium etidronate, bisphosphonates therapy is being considered for PAM. The disease is often silent till respiratory insufficiency supervenes. Rate of progression remains varied. Death often occurs in the fifth decade of life from respiratory insufficiency and cor pulmonale. With the limitations of a definitive medical management, lung transplantation is the only definitive intervention which has shown benefit in the end-stage cases of PAM with respiratory failure.[6] In the current issue of Lung India, Jindal et al. reported the first case of PAM from India undergoing lung transplantation.[7] A study of this case reveals an end-stage disease given the dependence on oxygen and non invasive ventillation (NIV). Lung transplant was the only management that could be offered to this patient to improve survival and quality of life. Since the first successful double-lung transplant in humans in 1988, the first successful bilateral lung transplant in PAM was performed in France in 1992. A current literature review reveals 19 cases of PAM undergoing lung transplant including the present case. The longest survival continued follow-up beyond 15 years (single-lung transplant done in Canada in 2001).[8] The optimal time for referring a patient of PAM for lung transplant is not defined yet by guidelines; however, it is prudent to refer the patient before the onset of severe right ventricular dysfunction.[6] It worth noting in the present case report that given the advanced stage of the disease the biventricular function was well preserved, and hence, the benefit of lung transplant is likely to be optimal. The argument of single versus double-lung transplant favors the latter for the fear of persistent shunting of blood through native lung with single lung transplant. The literature documents four single-lung transplants, of which three have survived beyond 12 months, including the longest surviving follow-up at 15 years. Taking the present case in consideration, of ten double-lung transplants, seven survived beyond 12 months.[6] Till date, no recurrence has been documented in transplanted lungs. The benefit of lung transplant outweighs the risks of morbidity due to immunosuppression in advanced cases of PAM. As our expertise in lung transplantation and posttransplant care continues to grow, we are likely to see improved survival and increasing number of referrals. It is worth emphasizing that of till 2015, India reported 80 of the 1022 cases worldwide. Since then, 27 cases have been reported, of which ten are from India, including the present case.[5910] With an increasing proportion of cases being reported from India, a national registry of this “orphan” disease will help us better study the trends and improve management by having timely referrals for lung transplant.
  7 in total

1.  Single lung transplantation for pulmonary alveolar microlithiasis.

Authors:  K B. Jackson; D L. Modry; J Halenar; J L'abbe; T L. Winton; D C. Lien
Journal:  J Heart Lung Transplant       Date:  2001-02       Impact factor: 10.247

2.  Pulmonary alveolar microlithiasis.

Authors:  R VISWANATHAN
Journal:  Thorax       Date:  1962-09       Impact factor: 9.139

Review 3.  Pulmonary alveolar microlithiasis: review of the 1022 cases reported worldwide.

Authors:  Giuseppe Castellana; Giorgio Castellana; Mattia Gentile; Roberto Castellana; Onofrio Resta
Journal:  Eur Respir Rev       Date:  2015-12

4.  Progressive Sandstorm Lung in Pulmonary Alveolar Microlithiasis.

Authors:  Chih-Wei Chen; Fu-Zong Wu
Journal:  Ann Thorac Surg       Date:  2018-08-04       Impact factor: 4.330

5.  Case series of Pulmonary Alveolar Microlithiasis from India.

Authors:  Manu Chopra; Manjit Sharad Tendolkar; Vasu Vardhan
Journal:  BMJ Case Rep       Date:  2019-03-22

6.  Pulmonary alveolar microlithiasis diagnosed with radiography, CT, and bone scintigraphy.

Authors:  Emad Alkhankan; Hasan Yamin; Hazim Bukamur; Fadi Alkhankan; Yousef Shweihat; Fuad Zeid
Journal:  Radiol Case Rep       Date:  2019-04-10

7.  Pulmonary alveolar microlithiasis: A rare disease treated with lung transplantation, first case from India.

Authors:  Apar Jindal; Vijil Rahulan; Govini Balasubramani; Prabhat Dutta; Sandeep Attawar
Journal:  Lung India       Date:  2019 Nov-Dec
  7 in total

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