Inflammation, Infection, and Pulmonary Function in Infants and Young Children with Cystic Fibrosis

Abstract

Our aim was to study the effect of lower airway infection on clinical parameters, pulmonary function tests, and inflammation in clinically stable infants and young children with cystic fibrosis (CF). To accomplish this goal, a prospective cohort of screened CF patients under 4 years of age were studied, using elective anesthesia and intubation for: passive respiratory mechanics (single breath occlusion passive deflation) and lung volumes (nitrogen washout), under neuromuscular blockade; and bronchoalveolar lavage (BAL) of 3 main bronchi for cytology, cytokine interleukin (IL)-8, and quantitative microbiology. There were 22 children studied, with a mean age of 23.2 months (6.7-44 months). A greater relative risk of lower airway pathogens was associated with prior respiratory admission (3.60, 95% confidence interval [CI] 2.87-4.51), history of asthma (1.75, 95% CI 1.52-2.03), and chronic symptoms (1.50, 95% CI 1.23-1.83), especially wheeze (1.88, 95% CI 1.61-2.19). Lower respiratory pathogens (> or = 10 cfu/ml BAL) were found in 14 out of 22, and greater than 10(5) cfu/ml in 8 out of 22 subjects. The level of pathogens in BAL (log10 cfu/ml) explained 78% of the variability in percent neutrophils and 34% of the variability in IL-8 levels. Pathogen level also correlated with pulmonary function tests of specific respiratory system compliance (r -0.49, p = 0.02) and functional residual capacity over total lung capacity (r 0.49, p = 0.03). We conclude that the presence of pathogens in the lower airways correlated with levels of inflammation, respiratory system compliance, and degree of air trapping.

Computed tomographic imaging of the airways: relationship to structure and function

“…Airway disease in CF is characterised by mucus plugging, chronic infection and an excessive inflammatory response, leading to peripheral airway changes in the first few months of life [101][102][103][104][105][106][107][108][109][110][111][112][113][114][115][116][117][118][119]. The characteristic airway abnormalities are bronchiectasis, thickening of the airway wall and mucus plugging [97,103,107,[120][121][122][123][124][125][126], as shown in figure 5.…”

Neutrophilic airway inflammation and IL‐17

“…There is evidence from clinical studies that an exaggerated recruitment and activation of neutrophilic granulocytes in the airways is linked to the clinical course of several inflammatory diseases in the airways and lungs, such as asthma (1)(2)(3)(4)(5)(6)82), nonspecific bronchial hyperreactivity (BHR) (7), chronic bronchitis (3,(8)(9)(10), chronic obstructive pulmonary disease (COPD) (3,(11)(12)(13), cystic fibrosis (14)(15)(16)(17), and acute respiratory distress syndrome (18)(19)(20). The referred evidence has been gathered analysing cellular contents in bronchial tissue, in bronchoalveolar lavage (BAL) fluid, in bronchial biopsies, in induced sputum and in peripheral blood.…”

Chronic pulmonary pseudomonal infection in patients with cystic fibrosis: A model for early phase symbiotic evolution

“…Furthermore, intestinal transit is largely dependent on peristalsis (not ciliary activity), and may improve postnatally with compensatory changes in muscular tone or other physiological adaptations. Shortly after birth, the nonfunctional CFTR in CF significantly impairs airway mucociliary function in individuals who otherwise show normal humoral and cellular immunity with no evidence of increased susceptibility to viral infection or malignancy (Abraham et al, 1996;Dakin et al, 2002;Noah et al, 1997;Sheldon et al, 1993). Although tissue destruction and toxin production have long been viewed as characteristic traits of pseudomonal virulence, Pa is an environmentally ubiquitous saprophyte.…”