Congenital Lung Abnormalities: Experience of a Tertiary Care NICU in Delhi, A Case Series

Respiratory distress is the most common cause of neonatal admission. Cystic lung lesions are rarer cause of the same. These are heterogeneous lesions with varied antenatal and postnatal manifestations. The outcomes of antenatally diagnosed lung malformations have showed more improvement than previously thought of. With advancement in imaging techniques, more definitive diagnosis and timely intervention, even in-utero interventions, can be planned. Overall, survival rates have also improved over the past 2 decades. A majority of infants are asymptomatic and do not require surgery in neonatal period, and the expectant management is usually followed in most centers, but some may have mass effect and require either in-utero or early neonatal intervention. For asymptomatic lesions, the timing of surgery remains controversial as there are propagators of both early and late intervention. A multidisciplinary team approach is required for its optimal management. We present here a set of 3 babies who were diagnosed as having cystic lung lesions antenatally but later these turned out to be completely different entities.

Differential Modulation of Matrix Metalloproteinases-2 and -7 in LAM/TSC Cells

Matrix metalloproteinase (MMP) dysregulation is implicated in several diseases, given their involvement in extracellular matrix degradation and cell motility. In lymphangioleiomyomatosis (LAM), a pulmonary rare disease, MMP-2 and MMP-9 have been detected at high levels in serum and urine. LAM cells, characterized by a mutation in the tuberous sclerosis complex (TSC)1 or TSC2, promote cystic lung destruction. The role of MMPs in invasive and destructive LAM cell capability has not yet been fully understood. We evaluated MMP-2 and MMP-7 expression, secretion, and activity in primary LAM/TSC cells that bear a TSC2 germline mutation and an epigenetic modification and depend on epidermal growth factor (EGF) for survival. 5-azacytidine restored tuberin expression with a reduction of MMP-2 and MMP-7 levels and inhibits motility, similarly to rapamycin and anti-EGFR antibody. Both drugs reduced MMP-2 and MMP-7 secretion and activity during wound healing and decreased their expression in lung nodules of a LAM mouse model. In LAM/TSC cells, MMP-2 and MMP-7 are dependent on tuberin expression, cellular adhesion, and migration. MMPs appears sensitive to rapamycin and anti-EGFR antibody only during cellular migration. Our data indicate a complex and differential modulation of MMP-2 and MMP-7 in LAM/TSC cells, likely critical for lung parenchyma remodeling during LAM progression.

Unusual Congenital Lesion Masquerading as a Lung Mass in an Adult

Congenital pulmonary airway malformation (CPAM) is a broad spectrum of congenital cystic lung lesions caused by the arrested bronchoalveolar development. Approximately, 80% of CPAMs are diagnosed prenatally or during the neonatal period when patients present with respiratory failure and cyanosis. CPAM is often associated with other organ anomalies and aplasia, and they have poor prognoses. Many CPAMs are detected in infants and school-age children, and infections like pneumonia trigger these diagnoses. It rarely manifests in adults. These often get missed because of the superadded diseases, and hence, it is essential to have a correct approach to their diagnosis to avoid misdiagnosis.

Pleuropulmonary Blastoma (PPB) in Child with DICER1 Mutation: The First Case Report in the State of Qatar

Pleuropulmonary blastoma (PPB) is a rare intrathoracic malignancy, which arises from the lung parenchyma and/or pleura. PPB has strong genetic association with mutations in DICER1 gene. Despite being rare, PPB is the most common lung tumor in children below 6 years of age. International registry of the disease has a total of 350 cases worldwide. We report the first case of PPB in the state of Qatar, which presented as a large cystic lung lesion. The patient was first thought to have benign congenital pulmonary airway malformation (CPAM) based on chest X-ray findings. The diagnosis of PPB was suspected based on chest CT scan findings and was confirmed after surgical resection of the cystic mass. The case highlights the need to consider PPB in the differential diagnosis of cystic lung lesions in children and the need for further radiological imaging (i.e., CT scan), genetic testing, and/or excisional biopsy to confirm the diagnosis.

The lung microbiome in end-stage Lymphangioleiomyomatosis

Lymphangioleiomyomatosis (LAM) is a progressive cystic lung disease with mortality driven primarily by respiratory failure. Patients with LAM frequently have respiratory infections, suggestive of a dysregulated microbiome. Here we demonstrate that end-stage LAM patients have a distinct microbiome signature compared to patients with end-stage chronic obstructive pulmonary disease.