Development of an anti-Pseudomonas aeruginosa therapeutic monoclonal antibody WVDC-5244.

The rise of antimicrobial-resistant bacterial infections is a crucial health concern in the 21st century. In particular, antibiotic-resistant Pseudomonas aeruginosa causes difficult-to-treat infections associated with high morbidity and mortality. Unfortunately, the number of effective therapeutic interventions against antimicrobial-resistant P. aeruginosa infections continues to decline. Therefore, discovery and development of alternative treatments are necessary. Here, we present pre-clinical efficacy studies on an anti-P. aeruginosa therapeutic monoclonal antibody. Using hybridoma technology, we generated a monoclonal antibody and characterized its binding to P. aeruginosa in vitro using ELISA and fluorescence correlation spectroscopy. We also characterized its function in vitro and in vivo against P. aeruginosa. The anti-P. aeruginosa antibody (WVDC-5244) bound P. aeruginosa clinical strains of various serotypes in vitro, even in the presence of alginate exopolysaccharide. In addition, WVDC-5244 induced opsonophagocytic killing of P. aeruginosa in vitro in J774.1 murine macrophage, and complement-mediated killing. In a mouse model of acute pneumonia, prophylactic administration of WVDC-5244 resulted in an improvement of clinical disease manifestations and reduction of P. aeruginosa burden in the respiratory tract compared to the control groups. This study provides promising pre-clinical efficacy data on a new monoclonal antibody with therapeutic potential for P. aeruginosa infections.

Congenital lobar emphysema: A rare cause of respiratory failure in neonates.

Congenital lobar overinflation, also known as congenital lobar emphysema (CLE), is an uncommon (1/20,000-30,000 live births) abnormality characterized by hyperinflation of one or more pulmonary lobes, usually with contralateral displacement of the mediastinum. While the etiology of most cases of CLE is poorly understood and labeled idiopathic, some cases are thought to be due to an intrinsic or extrinsic bronchial wall abnormality causing a ball valve mechanism with resultant hyperinflation of the affected lobe. CLE tends to have a predilection for males presenting insidiously in the first 6 months of life and have respiratory distress and progressive failure, with 50% of cases being asymptomatic at birth. Acquired forms of lobar emphysema are similar but are secondary to prolonged exposure to oxygen and positive pressure ventilation in premature infants. Clinical presentation is variable, ranging from wheezing, increased respiratory effort, cyanosis, feeding difficulties, and reflux or respiratory failure. Chest radiography (CXR) is the initial imaging obtained for any neonate with respiratory distress, which can aid in diagnosis showing overinflation, while computerized tomography (CT) remains the gold standard for confirmatory diagnosis. Treatment is variable and based on clinical severity. Some cases can be managed conservatively, while more severe cases require surgical intervention with lobectomy. Here, we present a case of a neonate in respiratory distress soon after birth, had initial improvement with supportive care, and was found to be secondary to CLE.

Diffuse alveolar hemorrhage in a pediatric patient with systemic lupus erythematosus.

A 15-year-old female patient was initially transferred due to symptomatic anemia following months of menorrhagia, fatigue, dyspnea, and weight loss. Early during her hospital course, pulmonary complications occurred with the development of respiratory failure secondary to bilateral pleural effusions. She was managed with bi-level pressure support ventilation alternating with a high-flow nasal cannula. An extensive workup resulted in a diagnosis of systemic lupus erythematosus: C3 level was 9 mg/dl (81-157 mg/dl) and her C4 level was 2 mg/dl (12-39 mg/dl); ANA titer was 1:5120 in a homogenous pattern. Scl-70 was qualitatively positive, quantitative anti-dsDNA level was 1044 IU/ml (<150 IU/ml), hemoglobin at presentation was 6.3 g/dl (11.8-15.7 g/dl), and her albumin level was 2.8 g/dl (3.5-5.0 g/dl). The patient was started on prednisone 60 mg daily and then transitioned to cyclophosphamide. Her symptoms improved initially; however, several days into admission she developed acute respiratory decompensation with blood-tinged sputum. Her hemoglobin levels, which had stabilized, began decreasing from 9.5 to 7.4 g/dl. Chest radiography showed new bilateral hazy infiltrates, and computerized tomography of the chest showed bilateral pleural effusions and parenchymal disease. A bronchoscopy confirmed a diagnosis of diffuse alveolar hemorrhage. The patient was treated with plasma exchange therapy and her corticosteroids were restarted. She completed a course of steroids and at initial pulmonology follow-up and showed stable pulmonary status with an improvement of her symptoms.

Recurrent spontaneous pneumothorax in a 15-year-old female associated with electronic cigarettes.

Pneumothorax as a sequela of vaping is a relatively recent complication being described in the literature. Smoking has classically been associated with an increased risk of pneumothorax, and emerging evidence is showing that electronic cigarettes (e-cigarettes) likely carry some of the same risks. Since e-cigarettes increased in popularity, especially among the adolescent population, there has been a reported increased incidence of lung injury, including pneumothorax. We present a case of a 15-year-old female with a history of e-cigarette use admitted for recurrent pneumothorax with failure to re-expand requiring surgical intervention.