Related Experiment Videos
Early pulmonary inflammation in infants with cystic fibrosis
T Z Khan1, J S Wagener, T Bost
1Department of Pediatrics, University of Colorado Health Science Center, Denver.
Insights
Early airway inflammation is present in infants with cystic fibrosis (CF). This study found increased inflammatory markers in CF infants, suggesting macrophages contribute to early lung damage in this disease.
Area of Science:
- Pulmonary Medicine
- Pediatric Respiratory Research
- Inflammation Biology
Background:
- The early mechanisms of lung disease in cystic fibrosis (CF) are not well understood.
- Neonatal screening identifies infants with CF, enabling early investigation of respiratory health.
Purpose of the Study:
- To investigate the presence and extent of airway inflammation in infants diagnosed with CF through neonatal screening.
- To identify potential cellular sources of inflammation, such as airway macrophages, in early CF lung disease.
Main Methods:
- Analyzed bronchoalveolar lavage fluid (BALF) from 16 infants with CF and 11 controls.
- Measured neutrophil count, neutrophil elastase activity, elastase/alpha 1-antiprotease inhibitor complexes, and interleukin-8 (IL-8) levels.
- Quantified IL-8 mRNA expression in airway macrophages.
Main Results:
- All measured inflammatory parameters were significantly elevated in infants with CF compared to controls.
- Increased neutrophils and IL-8 levels were observed even in CF infants with negative cultures for common pathogens.
- Airway macrophages showed increased IL-8 mRNA expression.
Conclusions:
- Airway inflammation is an early event in cystic fibrosis, detectable in infants as young as 4 weeks.
- Airway macrophages are a likely source of IL-8, contributing to neutrophil recruitment in the early stages of CF lung disease.
Abstract:
The mechanisms underlying the initiation of lung disease and early respiratory morbidity in cystic fibrosis (CF) are poorly understood. By identifying infants with CF through a statewide neonatal screening program, we investigated whether airway inflammation was present in these infants, with the goal of furthering our understanding of the early events in this lung disease. Bronchoalveolar lavage fluid (BALF) from 16 infants with CF (mean age, 6 mo) and 11 disease control infants (mean age, 12 mo) was examined for the following inflammatory parameters: (1) neutrophil count; (2) activity of free neutrophil elastase; (3) elastase/alpha 1-antiprotease inhibitor complexes; and (4) the level of interleukin-8 (IL-8). We also quantified the spontaneous level of expression of IL-8 mRNA transcripts by airway macrophages. Each index of airway inflammation was increased in the BALF of infants with CF as compared with control infants. In addition, both the number of neutrophils and IL-8 levels were increased in infants with CF who had negative cultures (n = 7) for common bacterial CF-related pathogens, as well as for common respiratory viruses and fungi at the time of bronchoalveolar lavage (BAL). These findings suggest that airway inflammation is already present in infants with CF who are as young as 4 wks. Furthermore, although many different cell types (e.g., epithelial cells) may express IL-8, airway macrophages appear to be a source of this chemokine, and may thus play a prominent role in early neutrophil influx into the lung.