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Vol. 35. Issue 2.
Pages 71-78 (February 1999)
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Vol. 35. Issue 2.
Pages 71-78 (February 1999)
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La suberosis: implicación de los mastocitos broncoalveolares en la génesis de la afectación intersticial
Suberosis: involvement of bronchoalveolar mast cells in the etiology of interstitial disease
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3897
L. Delgado1
Corresponding author
jdelgado@mail.telepac.pt

Correspondencia: Serviço de Imunologia. Faculdade de Medicina do Porto. 4200 Porto. Portugal.
, C. Cuesta, J.A. Fleming Torrinha
Servicio de Inmunología. Facultad de Medicina. Hospital de Sao João. Oporto
J.C. Winck*, J.M. Sapage*, J. Moura e Sá*
* Departamento de Neumología. Centro Hospitalario de Vila Nova de Gaia. Portugal
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La enfermedad respiratoria de los trabajadores de la industria del corcho –suberosis– puede presentarse clínicamente bajo la forma de neumonitis de hipersensibilidad (NH) o de enfermedad pulmonar obstructiva (EPO), con un cuadro asmatiforme o de bronquitis crónica. Los mastocitos son importantes células inflamatorias del pulmón que están particularmente implicadas en la liberación rápida de mediadores broncoconstrictores y en la producción de citocinas y mediadores que modulan la actividad de los fibroblastos. Se ha descrito un aumento del número de mastocitos en el lavado broncoalveolar (LBA) en las enfermedades pulmonares intersticiales, indicando su participación en la inflamación crónica y la fibrosis pulmonar.

Objetivos

El objetivo fue valorar la participación de los mastocitos en la inflamación pulmonar intersticial en los trabajadores de la industria del corcho analizando su presencia en el LBA por métodos histoquímicos. Con la posibilidad de una implicación de los mastocitos broncoalveolares en la patogénesis de la suberosis, también estudiamos su relación con los distintos cuadros clínicos de la enfermedad, con los parámetros funcionales respiratorios y con la intensidad de la alveolitis.

Pacientes y métodos

Treinta y un trabajadores de la industria del corcho con síntomas respiratorios relacionados con la exposición ocupacional, evaluados por la historia clínica y ocupacional, examen físico, radiografía de tórax, pletismografía corporal/espirometría, difusión de CO (DLCO), gasometría arterial en reposo y broncofibroscopia con LBA. La clasificación de los enfermos –20 con NH y 11 con EPO–se realizó según criterios clínicos, funcionales y del análisis del líquido del LBA. La cuantificación de los mastocitos fue realizada en frotis de citocentrifugado del LBA comparando dos tinciones distintas –May-Grunwald-Giemsa (MGG) y azul de toluidina (AzTol)– y los recuentos de dos observadores.

Principales resultados

Se confirmó una buena correlación entre los dos métodos de tinción (rs=0,86; p<0,0001) y entre los recuentos de dos observadores (MGG [rs=0,86] y AzTol [rs=0,87]; p<0,0001). El número de mastocitos en el LBA estaba significativamente más elevado en pacientes con NH (X±EPM, 13,4±4,5) que en los que tenían EPO (0,9±0,3; p<0,002, test de Mann-Whitney). El subgrupo de 8 pacientes con mayor compromiso funcional respiratorio -capacidad vital (CV) y/o DLCO<80% del valor esperado- presentaba también un número significativamente más elevado de mastocitos en el LBA (19,9±7,7 frente a 3,5±1,7; p=0,002). También encontramos una correlación negativa entre el número de mastocitos en el LBA y los parámetros funcionales respiratorios: capacidad pulmonar total (CPT) (rs=-0,63; p=0,005) y DLCO (rs=-0,54; p=0,008). El número de mastocitos recuperados en el LBA se correlacionó directa y significativamente con la intensidad de la alveolitis, la celularidad total (rs=0,62; p=0,002), el número absoluto de linfocitos (rs=0,56; p=0,006) y las concentraciones de albúmina (rs=0,68; p=0,003).

Conclusiones

Los resultados obtenidos indican que los mastocitos participan en la respuesta celular del intersticio pulmonar a la inhalación de polvos orgánicos del corcho, caracterizando particularmente las formas de NH. Por otro lado, su reclutamiento a la superficie broncoalveolar parece estar relacionado con la intensidad de la linfocitosis y de la inflamación del intersticio pulmonar, así como en el deterioro de la función respiratoria en estos pacientes.

Palabras clave:
Mastocitos
Suberosis
Neumonitis de hipersensibilidad
Lavado broncoalveolar

Suberosis –the lung disease suffered by cork industry workers– may present in the form of either hypersensitivity pneumonitis (HP) or obstructive pulmonary disease (OPD) with asthma-like symptoms or chronic bronchitis. Mast cells play an important role in pulmonary inflammation and are particularly implicated in the rapid release of mediators in bronchoconstriction and the production of cytokines and mediators of fibroblast activity. Increased numbers of mast cells are present in bronchoalveolar lavage (BAL) fluid in interstitial lung diseases, suggesting that these cells also participate in chronic inflammatory processes and in pulmonary fibrosis.

Objectives

To assess the participation of mas cells in in- terstitial pulmonary inflammation in cork industry workers by histochemically analyzing their presence in BAL fluid. Foresseing the possible implication of bronchoalveolar mast cells in the pathogenesis of suberosis, we also studied their relation to various signs and symptoms of the disease, to res- piratory function parameters and to degree of alveolitis.

Patients and methods

Thirty-one cork industry workers with respiratory symptoms related to occupational exposure were enrolled. Occupational and case histories were taken. Physical examiantions were complemented by chest X-rays, plethysmography/spirometry, fiberoptic bronchos- copy with BAL, and determination of carbon monoxide dif- fussing capacity (DLCO) and arterial blood gases at rest. Patient classification (20 with HP and 11 with OPD) was ba- sed on clinical and functional criteria and analysis of BAL fluid. Mast cells in cytospinned samples treated with two different stains [May-Grunwald-Giemsa (MGG) and Tolui- dine Blue (Tol.Bl.)] were counted by two observers and the results were compared.

Main results

Good correlation between the two staining methods was confirmed (rs=0.86, p<0.0001). Correlation between the two observers was also good (MGG rs=0.86, Yol.Bl. rs=0.87, p<0.0001). The number of mast cells in BAL fluid was significantly higher in patients with HP [13.4±4.5 (x±SEM)] than in those with OPD (0.9±0.3; p<0.002, Mann Whitney test). The subgroup of eight patinets with poorer respiratory function (CV and/or DLCO<80% of reference value) also had higher mast cell counts in BAL (19.9±7.7 versus 3.5±1.7; p=0.002). We also saw a negative relation between mast cell counts in BAL fluid and lung function parameters: total lung capacity (rs=-0.68, p=0.005) and DLCO (rs=-0.54, p=0.008). Mast cell recorvery from BAL fluid was positively related to severity of alveolitis in terms of total cell counts (rs=0.62, p=0.002), absolute lymphocyte counts (rs=0.56, p=0.006) and albumin levels (rs=0.68, p=0.003).

Conclusions

Our findings suggest that mast cells participate in interstitial lung cell response to the inhalation of organic cork dust, particularly when HP is the form of presentation. Moreover, mas cell recruitment on the alveolar surface seems to be related to the intersity of lymphocytosis and interstitial pulmonary inflammation and to lung function deterioration in affected patients.

Key words:
Mast cells
Suberosis
Hypersensitivity pneumonítis
Bronchoalveolur lavage
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