RESUMEN
Asthma and gastroesophageal reflux (GER) are commonly associated disorders. Microaspiration is one possible link between these processes. The purpose of this study was to assess methacholine reactivity following repeated small-volume aspiration such as may occur with GER. This was also correlated with airway cytology. Five weekly intratracheal instillations of either milk (N = 8) or saline sham controls (N = 7) in volumes of 0.25 mL/kg were performed in anesthetized rabbits. Transpulmonary pressure, flow, tidal volume, central airways resistance, and dynamic lung compliance were measured in anesthetized and paralyzed animals at baseline, after 2 and 5 weeks of instillation, and 3 weeks after the last instillation. Doubling concentrations of methacholine were given until a 50% or greater increase in resistance occurred (PC50R). Bronchial washings for cytological evaluation were performed after the physiologic measurements and before each instillation. There were no significant differences in airway reactivity between baseline and all subsequent observation points within each of the two groups. However, methacholine responsiveness was significantly higher in the milk group before the final instillation (PC50R = 5.84 vs. 12.97 mg/mL, P = 0.03) and at recovery (PC50R = 6.40 vs. 10.56 mg/mL, P = 0.047) when compared to saline controls. This was associated with a higher neutrophil percentage (P = 0.01) at 5 weeks, and eosinophil percentage (P = 0.05) at recovery in the bronchial wash specimens from the milk group. These results show that repeated small-volume aspiration of milk in rabbits causes persistent inflammation and is associated with greater airway reactivity when compared to sham controls. This inflammation was accompanied by either increased neutrophils or eosinophils in bronchial lavage specimens. These findings lend support to a possible role of microaspiration in association with increased airway reactivity in patients with GER.
Asunto(s)
Hiperreactividad Bronquial/etiología , Inhalación/fisiología , Leche , Animales , Hiperreactividad Bronquial/fisiopatología , Pruebas de Provocación Bronquial , Broncoconstrictores , Reflujo Gastroesofágico/fisiopatología , Cloruro de Metacolina , ConejosRESUMEN
High levels of lipid-laden macrophages (LLM) in bronchial washings have been associated with food aspiration. We studied the time course of appearance and clearance of LLM in rabbits undergoing either a single milk instillation, five weekly milk instillations or saline (control) instillations into the airways. Cells were obtained by bronchoalveolar lavage of intubated rabbits at uniform time intervals following the single or the last of five milk/saline instillations. LLM semi-quantitative indexes were derived using oil-red-O staining. Significantly elevated indexes were found in both milk groups 6 hr after milk instillation. In the single saline and milk instillation groups the indexes were not different beginning on the 4th day, and indexes from 8 of 9 rabbits had returned to baseline by the 6th day. However, indexes remained significantly elevated up to 17 days in the group receiving weekly milk instillations. Indexes from all rabbits in the repeat milk instillation group remained elevated for 12 days or longer. This group also developed increased numbers of binucleated macrophages. Quantitation of LLM in this model appears to be a sensitive indicator of recurrent lipid aspiration, these cells remaining in the airways for several days after the last aspiration event.
Asunto(s)
Líquido del Lavado Bronquioalveolar/citología , Células Espumosas/fisiología , Macrófagos Alveolares/fisiología , Leche , Neumonía por Aspiración/diagnóstico , Animales , Bovinos , Femenino , Masculino , Neumonía por Aspiración/fisiopatología , Conejos , Recurrencia , Factores de TiempoRESUMEN
We prospectively evaluated bronchial washings from 45 patients aged 1 month to 25 years (mean 3.3 years) for the presence of lipid-laden macrophages. By grading the amount of intracellular oil-red-O-positive material, we determined a semiquantitative lipid-laden macrophage index for each patient. All patients observed to be definite aspirators (n = 22) had indexes greater than or equal to 86 (mean +/- SD, 139 +/- 46). All patients with no clinical suspicion of aspiration (n = 23) had indexes less than or equal to 72 (mean +/- SD, 21 +/- 20). Our results suggest that simply sighting lipid-laden macrophages in a nonspecific finding, but quantitation of these cells may be a very good test for recurrent aspiration of food substances in children. This test appears to be more sensitive than radiographic studies.