Long-term clearance from small airways in patients with cystic fibrosis

Abstract

Impaired mucociliary clearance is a hallmark of cystic fibrosis (CF). Early morphological changes first appear in the small airways. Lung clearance was investigated in 11 young CF adults with mild-to-moderate lung disease using a method depositing particles mainly in the small airways.Radiolabelled Teflon particles (6 mm) were inhaled with an extremely slow inhalation flow, 0.05 L?s -1 . Lung retention was measured immediately following inhalations and, on four occasions up to 21 days. The results were compared with data from healthy subjects.The lung retention at 24 h in % of deposition was 67% (95% confidence interval 58-76) in the CF patients, compared to 48% (42-53) in the healthy subjects. Clearance on days 1-7 was larger in the CF patients, 22% (15-29) compared to the healthy subjects, 14% (12)(13)(14)(15)(16). No difference was observed between the CF patients and the healthy subjects in the slow clearance phase at day 7 to day 21, representing small airway clearance. Impaired mucociliary clearance in CF patients results in increased 24-h retention and a prolonged rapid clearance phase.The results of the study do not support the current authors' hypothesis that clearance from small airways is slower in cystic fibrosis patients compared to healthy subjects. Furthermore, the data suggest that mucociliary transport is not the dominant clearance mechanism in small airways.

Long-term clearance from small airways decreases with age

“…Subjects with cystic fibrosis and FEV1 ,70% were found to have worse long-term clearance compared with those with FEV1 .70% [36]. This indicates that there might also be an association between small airways clearance and development of airway obstruction.…”

CCSP regulates cross talk between secretory cells and both ciliated cells and macrophages of the conducting airway

“…Epithelial-derived host defense proteins include antioxidant, bacteriostatic, and bacteriolytic proteins as well as chemokines and cytokines that recruit immune system cells and modulate the immune response (20). The vital role for appropriately regulated epithelial responses in mucosal defense is highlighted by the potentially life-threatening sequelae of chronic inflammatory diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) (19,25). In such individuals, deviations in the normal inflammatory response have been correlated with a decline in the most abundant secreted product of nonciliated secretory cells, Clara cell secretory protein (CCSP/CC16), and increased abundance of annexin A1 (ANXA1)/lipocortin1 (2,10,27,30,38).…”

Contrast-enhanced 3D MRI of lung perfusion in children with cystic fibrosis—initial results

“…This is reflected in the presented cohort: patients had normal lung function or showed mainly mild or moderate obstructive lung disease although morphological changes were found in every patient. Furthermore, the pulmonary destruction process starts at the level of small airways [2,14,15]. PFTs are not reliable for measurement of smallairway function, thus assessment of early pulmonary changes is difficult [16].…”

“…Eleven patients (9 female, 2 male; median age 16 years, range [11][12][13][14][15][16][17][18][19] were prospectively examined at 1.5 T (Magnetom Symphony, Siemens Erlangen, Germany) equipped with a high-performance gradient system. None of the patients had clinical symptoms of exacerbation or needed therapy for exacerbation.…”