Definición, patogenia y factores de riesgo de la fibrosis pulmonar idiopática / Definition, pathogenesis and risk factors of idiopathic pulmonary fibrosis

La fibrosis pulmonar idiopática (FPI) es una forma específica de neumonía intersticial idiopática, de tipo fibrosante crónica y progresiva, con patrón radiológico y/o histológico de neumonía intersticial usual (NIU). Su patogenia es compleja, el modelo más aceptado actualmente es basado en las células epiteliales alveolares, aberrantemente activadas que conducen a la proliferación de fibroblastos y su diferenciación a miofibroblastos que depositan matriz extracelular y destruyen irreversiblemente la arquitectura pulmonar. No existe un claro factor inicial que explique la activación y posterior mantención del mecanismo de la fibrosis. El factor de crecimiento transformante beta (TGF-β) liberado por las células epiteliales alveolares se ha implicado como unos de los principales conductores de la inducción y proliferación de fibroblastos alterados que persiste mucho tiempo después de la estimulación inicial, lo que explicaría en gran parte el comportamiento clínico progresivo y crónico.

Idiopathic pulmonary fibrosis (IPF) is a specific form of idiopathic interstitial pneumonia, of chronic and progressive fibrosing type, with radiological and / or histological pattern of usual interstitial pneumonia (UIP). Its pathogenesis is complex, the most accepted model currently is based on the fact that the alveolar epithelial cells, aberrantly activated, lead to the proliferation of fibroblasts and their differentiation to myofibroblasts that deposit extracellular matrix and irreversibly destroy the pulmonary architecture. There is no clear initial trigger that explains the activation and subsequent maintenance of the fibrosis mechanism. The transforming growth factor beta (TGF-β), released by the alveolar epithelial cells, has been implicated as one of the main drivers of the induction and proliferation of altered fibroblasts that persists long after the initial stimulation, which would largely explain progressive and chronic clinical behavior.

¿El reflujo gastroesofágico y la aspiración de contenido gástrico están implicados en la etiopatogenia y la progresión de la fibrosis pulmonar idiopática? / Does gastroesophageal reflux and gastric content aspiration have some role in the pathogenesis and progression of Idiopathic Pulmonary Fibrosis?

Resumen El reflujo gastroesofágico (RGE) y la aspiración oculta de contenido digestivo están probablemente implicados en la etiopatogenia y progresión de la fibrosis pulmonar idiopática (FPI). Los mecanismos patogénicos involucrados son la disminución de la distensibilidad pulmonar y el consiguiente aumento de la presión negativa intratorácica durante la inspiración, así como la disminución de los mecanismos de control de la motilidad esofágica o del tono del esfínter esofágico inferior. La prevalencia de RGE y anomalías de la motilidad esofágica están aumentadas en los pacientes con FPI comparado con la población general. Entre los pacientes con FPI, el 67-76% demostraron exposición anormal al contenido ácido en el esófago. Sin embargo, no hubo relación entre la gravedad del RGE y la gravedad de la FPI. Los estudios que han examinado el tratamiento antirreflujo en esta población han sido escasos. Incluso, algunos datos sugieren que el tratamiento antiácido puede ser perjudicial en algunos pacientes con esta condición. Después de analizar toda la evidencia relevante encontrada hasta la fecha, concluimos que no se puede establecer una relación causal entre el RGE, la aspiración del contenido gástrico y la patogénesis de la FPI. Además, existe escasa evidencia clínica que haya examinado el tratamiento antirreflujo en pacientes con fibrosis pulmonar idiopática.

ABSTRACT Gastroesophageal reflux (GERD) and hidden aspiration of gastric contents are probably involved in the pathogenesis and progression of idiopathic pulmonary fibrosis (IPF). The pathological mechanisms involved are decreased pulmonary distensibility and consequent increase of intrathoracic negative pressure during inspiration, as well as decreased control mechanisms of esophageal motility or lower esophageal sphincter. The prevalence of GERD and oesophageal dysmotility was higher in patients with IPF as compared with general population. Among patients with IPF, 67-76% demonstrated abnormal oesophageal acid exposure. However, no relationship was demonstrated between severity of GERD and severity of IPF. Data are scant on outcomes of antireflux treatment in patients with IPF. Actually, some data suggests that antacid treatment may be deleterious in some IPF patients. After analyzing all the relevant evidence found to date, a causal relationship between GERD, gastric content aspiration and IPF pathogenesis cannot be established. There is scant evidence examining antireflux treatment in idiopathic pulmonary fibrosis patients.

Fibrose pulmonar idiopática simultânea a enfisema em pacientes tabagistas / Idiopathic pulmonary fibrosis and emphysema in smokers

OBJETIVO: Descrever os achados clínicos e funcionais de pacientes com enfisema em lobos superiores e fibrose pulmonar idiopática (FPI) em lobos inferiores, recentemente descrita na literatura. MÉTODOS: Um grupo de 11 pacientes com a presença simultânea de enfisema e FPI foi identificado retrospectivamente. Todos os pacientes realizaram tomografia computadorizada de tórax com alta resolução e provas de função pulmonar. RESULTADOS: Entre os 11 pacientes identificados, havia 8 homens e 3 mulheres, com média de idade de 70,7 ± 7,2 anos (variação, 61-86 anos). Todos os pacientes eram tabagistas (carga tabágica, 61,5 ± 43,5 anos-maço). As médias da capacidade vital forçada (CVF), do volume expiratório forçado no primeiro segundo (VEF1) e da relação VEF1/CVF foram 72,1 por cento ± 12,7 por cento, 68,2 por cento ± 11,9 por cento e 74,4 ± 10,8, respectivamente. Os volumes pulmonares foram normais em 7 pacientes. Um padrão restritivo foi observado em 3 pacientes e hiperinsuflação estava presente em um. A capacidade de difusão pulmonar apresentou redução moderada a grave em todos os pacientes (média, 27,7 por cento ± 12,9 por cento do previsto). No teste da caminhada de seis minutos, realizado por 10 pacientes, a distância caminhada média foi de 358,4 ± 143,1 m, ocorrendo dessaturação >4 por cento em 9 pacientes. Achados ecocardiográficos sugestivos de hipertensão pulmonar estavam presentes em 4 pacientes (média da pressão sistólica da artéria pulmonar, 61,8 mmHg; variação, 36-84 mmHg). CONCLUSÕES: A presença simultânea de enfisema e FPI causa alterações características nas provas de função pulmonar. O achado mais importante é a discrepância entre a capacidade de difusão e a espirometria.

OBJECTIVE: To describe the clinical and functional findings recently reported in the medical literature for patients diagnosed with emphysema involving the upper lobes and idiopathic pulmonary fibrosis (IPF) involving the lower lobes. METHODS: Eleven patients with emphysema and IPF were identified retrospectively. All of the patients underwent high-resolution computed tomography of the lung and pulmonary function tests. RESULTS: Of the 11 patients, 8 were male and 3 were female. The mean age was 70.7 ± 7.2 years (range, 61-86 years). All of the patients were smokers (mean smoking history, 61.5 ± 43.5 pack-years). The mean values of forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and FEV1/FVC were 72.1 percent ± 12.7 percent, 68.2 percent ± 11.9 percent and 74.4 ± 10.8, respectively. Lung volumes were normal in 7 patients. A restrictive pattern was observed in 3 patients, and hyperinflation was present in one. The diffusing capacity was moderately-to-severely reduced in all of the patients (mean, 27.7 percent ± 12.9 percent of predicted). Ten of the 11 patients performed the six-minute walk test. The mean distance covered was 358.4 ± 143.1 m, and 9 of the 10 patients presented desaturation > 4 percent. Echocardiographic findings suggestive of pulmonary hypertension were present in 4 patients (mean systolic pulmonary artery pressure, 61.8 mmHg; range, 36-84 mmHg). CONCLUSIONS: The concomitant presence of emphysema and IPF causes characteristic changes on pulmonary function tests. The most significant finding is a discrepancy between diffusing capacity and spirometry results.