Pulmonary Alveolar Microlithiasis Research Articles

(1274) - Lung Transplant in Pulmonary Alveolar Microlithiasis 2 Cases of Successful Treatment

(1274) - Lung Transplant in Pulmonary Alveolar Microlithiasis 2 Cases of Successful Treatment

(943) - Lung Transplantation Outcomes of Patients with Pulmonary Alveolar Microlithiasis the Largest Series from a Single Centre Experience

(943) - Lung Transplantation Outcomes of Patients with Pulmonary Alveolar Microlithiasis the Largest Series from a Single Centre Experience

Pulmonary alveolar microlithiasis: A case report.

An uncommon autosomal recessive condition called pulmonary alveolar microlithiasis (PAM) is characterized by the buildup of intra-alveolar calcifications inside the lung parenchyma. In this case report, a 16-year-old female patient with PAM is examined in-depth clinically and radiologically. The patient's radiographs revealed dense consolidation in both lungs. The diagnosis of PAM was confirmed by high-resolution computed tomography (HRCT), which showed bilateral, extensive and symmetrical distribution of the calcifications. We go over PAM's clinical presentation, imaging traits, diagnostic difficulties, and current therapeutic strategies. In order to provide a complete overview of this uncommon lung illness, we also evaluate relevant research.

Losing vigilance in diagnosing pulmonary alveolar microlithiasis: A report on four cases

Pulmonary alveolar microlithiasis (PAM) is a rare chronic lung disease characterized by calcium and phosphate deposition in the alveolar lumen throughout the parenchyma of both lungs, with predominance in the middle and lower lung fields. It is caused by mutations in the recessive gene, SLC34A2, on the autosomal chromosome. In this article, we characterize four cases of PAM and analyze the loss of diagnostic vigilance in two of them. Patients came to medical facilities with clinical manifestations such as cough, shortness of breath, chest pain, and fatigue. The initial diagnosis was unclear in two cases because the X-ray film’s quality was not good enough and the medical staff had little experience in clinical and chest X-ray interpretations for PAM. The definitive diagnosis was based on a combination of high-resolution computed tomography (CT) and bronchoalveolar lavage fluid testing. In addition, chest X-ray and high-resolution CT enable the assessment of the stage, progression, and severity of the disease. There is currently no specific treatment for PAM other than lung transplantation.

Pulmonary alveolar microlithiasis—a rare lung disease—diagnosed by transbronchial cryobiopsy

Pulmonary alveolar microlithiasis—a rare lung disease—diagnosed by transbronchial cryobiopsy

Microlithiase alvéolaire pulmonaire : à propos de deux cas familiaux au Maroc

Pulmonary alveolar microlithiasis (PAM) is a rare autosomal recessive disease. The majority of patients are asymptomatic. The disease is often diagnosed on routine radiological examination. We report two familial cases of PAM. A 17-year-old girl with a chest X-ray showing an alveolar syndrome, especially on the right side, a bronchointerstitial syndrome, and diffuse calcifications. The thoracic CT scan showed calcified micro- and macronodules with pleural and pericardial calcifications. Respiratory function tests showed restrictive syndrome and normal blood gas values suggestive if PAM, which was confirmed by the presence of microliths in bronchoalveolar lavage (BAL). Family investigation led to chest radiograph of a 14-year-old sister who was asymptomatic but presented with an aspect of "sandstorm" calcifications. PAM is known to be radio-clinically dissociative. In typical cases, radiology can suggest the diagnosis, which is often confirmed by SLC34A2 mutation or microliths in BAL or sputum. The prognosis is compromised in the long-term. The only effective treatment nowadays is lung transplantation.

Pulmonary Alveolar Microlithiasis in Moroccan Child: A Case Report

Background: Pulmonary alveolar microlithiasis (PAM) is a rare but not uncommon disease; it showed worldwide distribution either familial or sporadic, the most reported cases in Europe, especially in Turkey. The presence of round shaped little bodies containing concentric calcareous lamellas in pulmonary alveolus is the hallmark of the disease. With this study, we report a case of PAM in moroccan child, who complained of class 2 exertional dyspnoea with no significant personal or family history. On physical examination, there was no evidence of clubbing or cyanosis of the extremities. On auscultation, fine crackles were present bilaterally. Chest X-ray showed innumerable small dense nodules diffusely involving both lungs. High resolution CT scan showed extensive micro nodules, areas of diffuse ground glass attenuation, septal thickening and in some cases black pleural lines. The diagnosis confirmed by opened right lung biopsy and Broncho alveolar lavage, biopsy showed numerous lamellar (Calculi).

Severe pulmonary alveolar microlithiasis

This case presents a patient with severe pulmonary alveolar microlithiasis, a rare genetic condition affecting the sodium-dependent co-transporter of the type II pneumocytes. As the disease progress, calcium-phosphate microlithiases accumulate within the alveoli. This leads to a severe diffuse interstitial disease with classic sand-like calcifications on chest radiography. Lung transplantation remains the only cure.

Insights into pulmonary phosphate homeostasis and osteoclastogenesis emerge from the study of pulmonary alveolar microlithiasis

Pulmonary alveolar microlithiasis is an autosomal recessive lung disease caused by a deficiency in the pulmonary epithelial Npt2b sodium-phosphate co-transporter that results in accumulation of phosphate and formation of hydroxyapatite microliths in the alveolar space. The single cell transcriptomic analysis of a pulmonary alveolar microlithiasis lung explant showing a robust osteoclast gene signature in alveolar monocytes and the finding that calcium phosphate microliths contain a rich protein and lipid matrix that includes bone resorbing osteoclast enzymes and other proteins suggested a role for osteoclast-like cells in the host response to microliths. While investigating the mechanisms of microlith clearance, we found that Npt2b modulates pulmonary phosphate homeostasis through effects on alternative phosphate transporter activity and alveolar osteoprotegerin, and that microliths induce osteoclast formation and activation in a receptor activator of nuclear factor-κB ligand and dietary phosphate dependent manner. This work reveals that Npt2b and pulmonary osteoclast-like cells play key roles in pulmonary homeostasis and suggest potential new therapeutic targets for the treatment of lung disease.

СОЧЕТАНИЕ ЛЕГОЧНОГО АЛЬВЕОЛЯРНОГО МИКРОЛИТИАЗА И ПНЕВМОКОНИОЗА – КЛИНИЧЕСКИЙ СЛУЧАЙ

Pulmonary alveolar microlithiasis is a rare genetic disease characterized by the formation of intraalveolar calcium phosphate microliths. Clinical and radiological manifestations are similar to pneumoconiosis, which makes it difficult to diagnose a comorbid condition. This article presents a case from clinical practice: a 30-year-old male patient, non-smoker was referred to a occupational pathology center with a preliminary diagnosis of pneumoconiosis. He worked for 8 years under conditions of exposure to highly fibrogenic dust with the maximum allowable concentrations in the air of the working area exceeding by 2.3–2.1 times. During this period, preliminary and 3 periodic medical examinations were carried out which did not reveal any contraindications for continuing work. Examination at the center of occupational pathologists revealed signs of respiratory failure of the 2nd degree, severe pulmonary hypertension and radiological diffuse dissemination syndrome with small shading of two types - a large number of high (calcium) density foci with clear edges and a moderate number of medium density foci. Histological examination revealed signs of pulmonary fibrosis and interstitial inflammation of the type of nonspecific interstitial pneumonia, microliths located intraalveolarly, as well as a small amount of granulomas with hyalinosis in the center, a concentric arrangement of collagen fibers, fibroblasts, alveolar macrophages. A comorbid disease was diagnosed – pulmonary alveolar microlithiasis in combination with pneumoconiosis confirmed by the results of genetic testing – the c.1328delT mutation of the SLC34A2 gene was detected. The further course of the disease was characterized by progression of dyspnea and desaturation, an increase in the number of high-density foci in the lungs. 2 years after diagnosis – death due to respiratory failure. The presented case demonstrates the possibility of a combination of pulmonary alveolar microlithiasis with pneumoconiosis and an unfavorable prognosis of a comorbid disease.

Pulmonary alveolar microlithiasis at female patient

Pulmonary alveolar microlithiasis at female patient

Bronchoalveolar Lavage in Diagnostic Evaluation of Pulmonary Diseases- An Institutional Experience.

Bronchoalveolar lavage (BAL) is a widely accepted investigative tool for the diagnosis of pulmonary lesions. This study was done to find out the usefulness of BAL in diagnosis of pulmonary lesions from central Indian patient population. A cross-sectional prospective study was performed over a period of three years. All the BAL specimens of patients presenting to Department of Pulmonary Medicine and Tuberculosis during a period of January 2017 to December 2019 were included in the study. Cyto-histopathologic correlation was done, wherever available. Of total 277 cases, there were 178 (64.5%) males and 99 (35.5%) females. The age of patients ranged from 4 years to 82 years. In 92 (33%) cases, specific infective etiology could be identified on BAL cytology, the most common being tuberculosis (26%) followed by fungal infections (2%). Rarely, infections like nocardia, actinomycosis, and hydatidosis were also identified. Eight cases (3%) of malignancy were identified which included two cases of adenocarcinoma, one case of small cell carcinoma, three cases of poorly differentiated carcinoma, and two cases suspicious for malignancy. Some rare diagnoses like diffuse alveolar damage, pulmonary alveolar microlithiasis, and pulmonary alveolar proteinosis could be identified on BAL. BAL is useful in primary diagnosis of infections and malignancies of lower respiratory tract. BAL may aid in diagnostic workup of diffuse lung diseases. A combination of clinical information, high-resolution computed tomography, and BAL analysis may furnish an assured diagnosis to the clinician and obviate need for invasive procedures.

Pharmacology of Mammalian Na+-Dependent Transporters of Inorganic Phosphate.

Inorganic phosphate (Pi) is an essential component of many biologically important molecules such as DNA, RNA, ATP, phospholipids, or apatite. It is required for intracellular phosphorylation signaling events and acts as pH buffer in intra- and extracellular compartments. Intestinal absorption, uptake into cells, and renal reabsorption depend on a set of different phosphate transporters from the SLC20 (PiT transporters) and SLC34 (NaPi transporters) gene families. The physiological relevance of these transporters is evident from rare monogenic disorders in humans affecting SLC20A2 (Fahr's disease, basal ganglia calcification), SLC34A1 (idiopathic infantile hypercalcemia), SLC34A2 (pulmonary alveolar microlithiasis), and SLC34A3 (hereditary hypophosphatemic rickets with hypercalciuria). SLC34 transporters are inhibited by millimolar concentrations of phosphonoformic acid or arsenate while SLC20 are relatively resistant to these compounds. More recently, a series of more specific and potent drugs have been developed to target SLC34A2 to reduce intestinal Pi absorption and to inhibit SLC34A1 and/or SLC34A3 to increase renal Pi excretion in patients with renal disease and incipient hyperphosphatemia. Also, SLC20 inhibitors have been developed with the same intention. Some of these substances are currently undergoing preclinical and clinical testing. Tenapanor, a non-absorbable Na+/H+-exchanger isoform 3 inhibitor, reduces intestinal Pi absorption likely by indirectly acting on the paracellular pathway for Pi and has been tested in several phase III trials for reducing Pi overload in patients with renal insufficiency and dialysis.

HPR30 Too Ultra-Rare for Care? Orphan Drug Availability for People Living With Ultra-Rare Respiratory Diseases in the Pre, Present and Post Pandemic Worlds

To compare the current and potential availability of treatments for seven index ultra-rare respiratory diseases before and after the peak of the COVID-19 pandemic. At the 2019 ISPOR EU Conference, a landscape review of available treatments for ultra-rare respiratory diseases was presented. Therefore, 3 years on, we sought to explore if treatment access has improved for ultra-rare respiratory diseases. A landscape review was undertaken to seek evidence of treatment developments for ataxia telangiectasia (AT), lymphangiomatosis (LYMF), pulmonary alveolar proteinosis (PAP), pleuroparenchymal fibroelastosis (PPFE), pulmonary alveolar microlithiasis (PAM), pulmonary dendriform ossification (PDO), and light chain deposition disorders (LCDD). Information from clinicaltrials.gov, orpha.net, the EMA and FDA archives and websites of five health technology assessment (HTA) bodies was narratively synthesised. The 2019 clinicaltrials.gov search identified 24 studies and the 2022 search 25 studies at various stages of the clinical trial process. They concerned PAP (2019/2022: 11/10), AT (6/10), LCDD (5/4), LYMF (1/0) and PPFE (1/1). No studies were identified for PAM or PDO. The 2019 review found treatments for AT and PAP were granted orphan status by the EMA and the FDA, and in 2021 the FDA granted orphan status to another AT treatment. Neither search found reimbursement submissions for any of the ultra-rare respiratory disease. There still remains an obvious lack of proven and available treatments for ultra-rare respiratory diseases. Over the past 3 years, only 1 new treatment has been granted regulatory approval and no treatments have yet to result in therapies that are licensed or approved by HTA bodies. It is our hope that as we enter the post-pandemic world, we as industry professionals and researchers start to adequately address the treatment needs of people living with these debilitating conditions.

Spectrum of Clinical Presentation of Pulmonary Alveolar Microlithiasis: Case Series from North India

We describe five cases of pulmonary alveolar microlithiasis (PAM) from North India with characteristic radiological and histopathological features. All patients were symptomatic with variable severity and duration of the symptoms and one patient developed cor-pulmonale during the course of follow-up. Diagnosis of PAM was suspected on the basis of classical sand-storm appearance on radiological examination and confirmed by transbronchial lung biopsy in four of the five cases. Apart from other features, presence of pleural and pericardial calcification in one case makes this discussion valuable. Awareness of this specific entity among the clinicians is essential to avoid unnecessary investigations.

Diagnostic Images of Pulmonary Alveolar Microlithiasis: A Rare, Autosomal Recessive Disorder.

Pulmonary alveolar microlithiasis (PAM) is a rare genetic lung disorder resulting in accumulation of calcium phosphate deposits in the alveoli.The typical radiological presentation of PAM is the classic 'sandstorm' appearance in the lung.The key to diagnosis of this disease is clinical-radiological dissociation.

Pulmonary alveolar microlithiasis: A case report from Morocco with review of literature

Background: Pulmonary alveolar microlithiasis (PAM) is a rare infiltrative chronic lung disease characterized by deposition of spherical calcium phosphate microliths called calcospherites within the alveoli with predominance in lower and mid zones. Etiology and pathogenesis is not fully understood. Case presentation: We report a case of 58 year old female patient presenting with progressive shortness of breath and chronic bronchitis over a period of 4 years. Physical examination revealed she had signs of chronic respiratory failure. Chest radiograph showed dense micronodular opacities giving classical sandstorm appearance. High resolution computed tomography showed diffuse microcalcifications, bilateral ground glass attenuation and septal thickening with calcification along the interlobar septa and subpleural regions. Conclusion: According to our research this is the 15th case of PAM that has been declared in Morocco. Given the rarity of this entity, the purpose of this study was to increase knowledge of this disease among pulmonologists, in order to provide timely diagnosis.

Pulmonary alveolar microlithiasis: A case report from Morocco with review of literature

Pulmonary alveolar microlithiasis: A case report from Morocco with review of literature

Pulmonary Alveolar Microlithiasis in a Patient with Ellis-van Creveld Syndrome.

"Pulmonary Alveolar Microlithiasis in a Patient with Ellis–van Creveld Syndrome." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp. –

Pulmonary alveolar microlithiasis caused by SLC34A2 gene compound heterozygous variations in a child

11岁患儿因“发现肺部影像学异常1年余”入院。完善基因检测提示SLC34A2基因存在复合杂合变异c.286C>T（exon4）、c.910A>T（exon8），变异分别来源于患儿父亲和母亲，诊断为SLC34A2复合杂合变异致肺泡微石症。.