T1 Lymphocytic bronchoalveolitis in idiopathic chronic cough

S.S. Birring, C.E. Brightling, F.A. Symon, S. Barlow, A.J. Wardlaw, I.D. Pavord. Institute For Lung Health, Glenfield Hospital, Leicester

We have recently reported an excess of cases of organ specific autoimmune diseases amongst patients with idiopathic chronic cough and have suggested that the cough may be due to homing of activated lymphocytes from the primary site of autoimmune inflammation to the lung. We tested this hypothesis in comparative immunopathology study of 19 patients with idiopathic chronic cough recruited over a two year period (mean age 54y, 79% female, mean duration of cough 2y), 11 healthy subjects and 14 patients with explained chronic cough of similar severity. Organ specific autoimmune disease was present in six of idiopathic cough patients (32%) but no normals/explained cough subjects. All subjects had a bronchoscopy, bronchoalveolar lavage (BAL) and bronchial biopsy using standard techniques.

We obtained cytospins from the BAL for a differential cell count and studied BAL T-cell status (CD4/8), activation (CD103, CD25, CD49a, HLA-DR) and chemokine receptors (CCR3,5,6,11, CXCR3) using 3-colour flow cytometry. Bronchial biopsies were embedded in glycolmethacrylate and immunohistochemistry for CD3,4,8 (lymphocytes), CD14 (monocytes), CD45 (leukocytes), CD56 (NK cells), EG2 (eosinophils), Neutrophil Elastase (neutrophils), AA1 (mast cells), Interferon-γ, IL5, 3H4(IL4) was performed. The mean (SEM) BAL differential lymphocyte count was 6.8 (1.3)% in normals, 15.1 (2.6)% in idiopathic cough (mean difference from normals 8.3%; 95% Confidence Interval 1.6 to 15.0; p<0.02) and 7.0(1.7)% in explained cough. The proportion of BAL T-cells expressing CD4 was similar in all three groups and there were no differences in activation status of T-cells or chemokine receptor expression. CD56 and IFNγ expression in biopsies (cells/mm² submucosa) were reduced in subjects with idiopathic cough compared to normals and subjects with explained cough (p=0.03 and 0.047: Kruskal-Wallis). EG2 and 3H4 expression were raised in explained cough (p=0.02 & …