Azithromycin Partially Mitigates Dysregulated Repair of Lung Allograft Small Airway Epithelium.

BACKGROUND: Dysregulated airway epithelial repair following injury is a proposed mechanism driving posttransplant bronchiolitis obliterans (BO), and its clinical correlate bronchiolitis obliterans syndrome (BOS). This study compared gene and cellular characteristics of injury and repair in large (LAEC) and small (SAEC) airway epithelial cells of transplant patients. METHODS: Subjects were recruited at the time of routine bronchoscopy posttransplantation and included patients with and without BOS. Airway epithelial cells were obtained from bronchial and bronchiolar brushing performed under radiological guidance from these patients. In addition, bronchial brushings were also obtained from healthy control subjects comprising of adolescents admitted for elective surgery for nonrespiratory-related conditions. Primary cultures were established, monolayers wounded, and repair assessed (±) azithromycin (1 µg/mL). In addition, proliferative capacity as well as markers of injury and dysregulated repair were also assessed. RESULTS: SAEC had a significantly dysregulated repair process postinjury, despite having a higher proliferative capacity than large airway epithelial cells. Addition of azithromycin significantly induced repair in these cells; however, full restitution was not achieved. Expression of several genes associated with epithelial barrier repair (matrix metalloproteinase 7, matrix metalloproteinase 3, the integrins ß6 and ß8, and ß-catenin) were significantly different in epithelial cells obtained from patients with BOS compared to transplant patients without BOS and controls, suggesting an intrinsic defect. CONCLUSIONS: Chronic airway injury and dysregulated repair programs are evident in airway epithelium obtained from patients with BOS, particularly with SAEC. We also show that azithromycin partially mitigates this pathology.

Obliterative bronchiolitis in workers in a coffee-processing facility - Texas, 2008-2012.

Obliterative bronchiolitis, a rare, irreversible form of fixed obstructive lung disease, has been identified in workers exposed to flavoring chemicals while working in the microwave-popcorn and flavoring-manufacturing industries; the occupational risk to workers outside these industries is largely unknown. This report describes two cases of obliterative bronchiolitis identified in workers employed in a small coffee-processing facility. Both patients' illness was misdiagnosed before they received a diagnosis of work-related obliterative bronchiolitis, which had not been identified previously in the coffee-processing industry. These cases reinforce the need for exposure evaluation in all industries in which workers are exposed to flavoring chemicals. Additionally, a high index of suspicion is required when these potentially exposed workers have progressive shortness of breath. If obliterative bronchiolitis is suspected, immediate protection from further exposure is crucial to prevent further deterioration of lung function.

Proteomic bronchiolitis obliterans syndrome risk monitoring in lung transplant recipients.

BACKGROUND: Obliterative bronchiolitis poses a primary obstacle for long-term survival of lung transplant recipients and manifests clinically as bronchiolitis obliterans syndrome (BOS). Establishing a molecular level screening method to detect BOS-related proteome changes before its diagnosis by forced expiratory volume surrogate marker criteria was the main objective of this study. METHODS: Bronchoalveolar lavage was performed in 82 lung transplant recipients (48/34 with/without known BOS development) at different time points between 12 and 48 months after lung transplantation. A mass spectrometry-based method was devised to generate bronchoalveolar lavage fluid proteome profiles that were screened for BOS-specific alterations. Statistically significant marker peptides and proteins were identified and validated by in-gel digestion, tandem mass spectrometric sequencing, and quantitative immunoassays. RESULTS: Among the panel of statistically significant markers were Clara cell protein, calgranulin A, human neutrophil peptides, and the antimicrobial agent histatin. To assess their clinical relevance, a highly sensitive and specific classifier model was developed. Positive BOS classification by monitoring of seven polypeptides correlated strongly with a significant decrease in BOS-free time. Thus, it was possible to detect high-risk patients early on in the pathogenetic process. CONCLUSIONS: Monitoring the bronchoalveolar lavage fluid levels of seven polypeptides detected by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry allows a reliable prediction of early BOS using a Random Forest decision tree-based classifier model. The high accuracy of this robust model and its synergistic potential in combination with established forced expiratory volume-based diagnostics could make it an effective tool to supplement the current diagnostic regime after multicentric validation.

Hiperplasia nodular linfoide en un paciente con inmunodeficiencia combinada grave / Lymphoid nodular hyperplasia in a patient with severe combined immunodeficiency disease

Describimos un caso de hiperplasia nodular linfoide en el contexto de un cuadro de inmunodeficiencia combinada grave. La paciente refería estreñimiento y crisis de dolor abdominal, presentando en la exploración una voluminosa masa abdominal. Los exámenes radiológicos iniciales hicieron sospechar el diagnóstico, pero fue necesaria la realización de una biopsia intestinal con el fin de descartar una afectación linfomatosa. Queremos llamar la atención sobre la semiología radiológica de esta entidad, que si bien en principio puede ser un hallazgo casual sin significado patológico, requiere una especial atención especialmente en sujetos inmunodeficientes (AU)