Distinct patterns of inflammation in the airway lumen and bronchial mucosa of children with cystic fibrosis.
BACKGROUND
Studies in cystic fibrosis (CF) generally focus on inflammation present in the airway lumen. Little is known about inflammation occurring in the airway wall, the site ultimately destroyed in end-stage disease.


OBJECTIVE
To test the hypothesis that inflammatory patterns in the lumen do not reflect those in the airway wall of children with CF.


METHODS
Bronchoalveolar lavage (BAL) fluid and endobronchial biopsies were obtained from 46 children with CF and 16 disease-free controls. BAL cell differential was assessed using May-Gruenwald-stained cytospins. Area profile counts of bronchial tissue immunopositive inflammatory cells were determined.


RESULTS
BAL fluid from children with CF had a predominance of neutrophils compared with controls (median 810×10(3)/ml vs 1×10(3)/ml, p<0.0001). In contrast, subepithelial bronchial tissue from children with CF was characterised by a predominance of lymphocytes (median 961 vs 717 cells/mm(2), p=0.014), of which 82% were (CD3) T lymphocytes. In chest exacerbations, BAL fluid from children with CF had more inflammatory cells of all types compared with those with stable disease whereas, in biopsies, only the numbers of lymphocytes and macrophages, but not of neutrophils, were higher. A positive culture of Pseudomonas aeruginosa was associated with higher numbers of T lymphocytes in subepithelial bronchial tissue (median 1174 vs 714 cells/mm(2), p=0.029), but no changes were seen in BAL fluid. Cell counts in BAL fluid and biopsies were positively correlated with age but were unrelated to each other.


CONCLUSIONS
The inflammatory response in the CF airway is compartmentalised. In contrast to the neutrophil-dominated inflammation present in the airway lumen, the bronchial mucosa is characterised by the recruitment and accumulation of lymphocytes.
Department of Paediatric Respiratory Medicine, Royal Brompton Hospital, London, UK. nicolas.regamey@insel.ch
Nicolas
N
Regamey
Lemonia
L
Tsartsali
Tom N
TN
Hilliard
Oliver
O
Fuchs
Hui-Leng
HL
Tan
Jie
J
Zhu
Yu-Sheng
YS
Qiu
Eric W F W
EW
Alton
Peter K
PK
Jeffery
Andrew
A
Bush
Jane C
JC
Davies
D000293:Adolescent; D000367:Age Factors; D056151:Airway Remodeling / Q000502:physiology; D001706:Biopsy; D001980:Bronchi / Q000473:pathology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000150:complications / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D007223:Infant; D016131:Lymphocyte Subsets / Q000276:immunology; D008297:Male; D009894:Opportunistic Infections / Q000150:complications / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D011014:Pneumonia / Q000150:complications* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D012129:Respiratory Function Tests; D020545:Respiratory Mucosa / Q000276:immunology / Q000473:pathology; D014797:Vital Capacity / Q000502:physiology
C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator