Characterization of the innate immune response to chronic aspiration in a novel rodent model

<p>Abstract</p> <p>Background</p> <p>Although chronic aspiration has been associated with several pulmonary diseases, the inflammatory response has not been characterized. A novel rodent model of chronic aspiration was therefore developed in order to investigate the resulting innate immune response in the lung.</p> <p>Methods</p> <p>Gastric fluid or normal saline was instilled into the left lung of rats (n = 48) weekly for 4, 8, 12, or 16 weeks (n = 6 each group). Thereafter, bronchoalveolar lavage specimens were collected and cellular phenotypes and cytokine concentrations of IL-1alpha, IL-1beta, IL-2, IL-4, IL-6, IL-10, GM-CSF, IFN-gamma, TNF-alpha, and TGF-beta were determined.</p> <p>Results</p> <p>Following the administration of gastric fluid but not normal saline, histologic specimens exhibited prominent evidence of giant cells, fibrosis, lymphocytic bronchiolitis, and obliterative bronchiolitis. Bronchoalveolar lavage specimens from the left (treated) lungs exhibited consistently higher macrophages and T cells with an increased CD4:CD8 T cell ratio after treatment with gastric fluid compared to normal saline. The concentrations of IL-1alpha, IL-1beta, IL-2, TNF-alpha and TGF-beta were increased in bronchoalveolar lavage specimens following gastric fluid aspiration compared to normal saline.</p> <p>Conclusion</p> <p>This represents the first description of the pulmonary inflammatory response that results from chronic aspiration. Repetitive aspiration events can initiate an inflammatory response consisting of macrophages and T cells that is associated with increased TGF-beta, TNF-alpha, IL-1alpha, IL-1beta, IL-2 and fibrosis in the lung. Combined with the observation of gastric fluid-induced lymphocyitic bronchiolitis and obliterative bronchiolitis, these findings further support an association between chronic aspiration and pulmonary diseases, such as obliterative bronchiolitis, pulmonary fibrosis, and asthma.</p

Prevalência de refluxo gastroesofágico em pacientes com doença pulmonar avançada candidatos a transplante pulmonar Prevalence of gastroesophageal reflux in lung transplant candidates with advanced lung disease

OBJETIVO: Avaliar o perfil funcional do esôfago e a prevalência de refluxo gastroesofágico (RGE) em pacientes candidatos a transplante pulmonar. MÉTODOS: Foram analisados prospectivamente, entre junho de 2005 e novembro de 2006, 55 pacientes candidatos a transplante pulmonar da Santa Casa de Misericórdia de Porto Alegre. Os pacientes foram submetidos a esofagomanometria estacionária e pHmetria esofágica ambulatorial de 24 h de um e dois eletrodos antes de serem submetidos ao transplante pulmonar. RESULTADOS: A esofagomanometria foi anormal em 80% dos pacientes e a pHmetria revelou RGE ácido patológico em 24%. Os sintomas digestivos apresentaram sensibilidade de 50% e especificidade de 61% para RGE. Dos pacientes com doença pulmonar obstrutiva crônica, 94% apresentaram alteração à manometria, e 80% apresentaram hipotonia do esfíncter inferior, que foi o achado mais freqüente. Pacientes com bronquiectasias apresentaram a maior prevalência de RGE (50%). CONCLUSÕES: O achado freqüente em pacientes com doença pulmonar avançada é RGE. Na população examinada, a presença de sintomas digestivos de RGE não foi preditiva de refluxo ácido patológico. A contribuição do RGE na rejeição crônica deve ser considerada e requer estudos posteriores para seu esclarecimento.<br>OBJECTIVE: To assess the esophageal function profile and the prevalence of gastro-esophageal reflux (GER) in lung transplant candidates. METHODS: From July of 2005 to November of 2006, a prospective study was conducted involving 55 candidates for lung transplantation at the Santa Casa de Misericórdia Hospital in Porto Alegre, Brazil. Prior to transplantation, patients underwent outpatient stationary esophageal manometry and 24-h esophageal pH-metry using one and two electrodes. RESULTS: Abnormal esophageal manometry was documented in 80% of the patients, and 24% of the patients presented pathological acid reflux. Digestive symptoms presented sensitivity and specificity for GER of 50% and 61%, respectively. Of the patients with chronic obstructive pulmonary disease, 94% presented abnormal esophageal manometry, and 80% presented lower esophageal sphincter hypotonia, making it the most common finding. Patients with bronchiectasis presented the highest prevalence of GER (50%). CONCLUSIONS: In patients with advanced lung disease, GER is highly prevalent. In the population studied, digestive symptoms of GER were not predictive of pathological acid reflux. The role that GER plays in chronic rejection should be examined and clarified in future studies