Biomarkers in exhaled breath condensate indicate presence and severity of cystic fibrosis in children (original) (raw)
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PLOS ONE, 2016
Background Cystic Fibrosis (CF) is characterized by chronically inflamed airways, and inflammation even increases during pulmonary exacerbations. These adverse events have an important influence on the well-being, quality of life, and lung function of patients with CF. Prediction of exacerbations by inflammatory markers in exhaled breath condensate (EBC) combined with early treatment may prevent these pulmonary exacerbations and may improve the prognosis. Aim To investigate the diagnostic accuracy of a set of inflammatory markers in EBC to predict pulmonary exacerbations in children with CF. Methods In this one-year prospective observational study, 49 children with CF were included. During study visits with an interval of 2 months, a symptom questionnaire was completed, EBC was collected, and lung function measurements were performed. The acidity of EBC was measured directly after collection. Inflammatory markers interleukin (IL)-6, IL-8, tumor necrosis factor α (TNF-α), and macrophage migration inhibitory factor (MIF) were measured PLOS ONE |
Journal of Comprehensive Pediatrics, 2019
Background: Exhaled nitric oxide (FeNO) in cystic fibrosis (CF) patients is reduced when compared with healthy people, and it has now been found that FeNO has a relative association with airway clearance index. Studies have shown the role of some infections in changing the FeNO level; however, the role of respiratory infections in FeNO has not yet been thoroughly studied. Objectives: The objective of this study was to investigate the possibility of FeNO usage to monitor the infections in CF patients. Methods: This cross-sectional case-control study was conducted on CF patients between the age of five to 18 with positive sputum culture, through simple non-random census method. FeNO levels were measured in 30 healthy children and 30 CF children with positive sputum culture. CF patients were treated by antibiotic therapy for two weeks; in the case offending negative sputum culture, the FeNO level was re-measured. FeNO levels were re-evaluated in 13 patients after four weeks. Results: There was no statistical difference between both groups in terms of age and weight. The level of FeNO in CF patients was significantly lower than in healthy children (22.1 ± 10.1 versus 30.0 ± 11.0 in the control group and P = 0.003). In 27 children, two weeks after administration of antibiotic therapy, sputum culture was negative. The mean of FeNO in these patients was 16.4 ± 5.5 at the time of the negative sputum culture, which was significantly lower than FeNO before starting the treatment. (P: 0.003). The mean FeNO was 13.0 ± 7.41 in 13 patients who were re-measured four weeks after starting the treatment. There was no significant difference between FeNO level two weeks after treatment and four weeks after starting treatment (P: 0.292). Patients with pseudomona sputum culture were not significantly different from those with non-pseudomona sputum culture in terms of primary FeNO and FeNO changes after the treatment (P value: 0.084 and 0.094, respectively). Conclusions: However, in our study, FeNO was decreased after administration of antibiotic treatment in CF patients, but according to the sample size and conflicting or similar results in other studies, currently, FeNO levels cannot be used as a way of monitoring the treatment of infection in CF patients.
Journal of Inflammation Research, 2013
Bronchiectasis is an airway disease characterized by thickening of the bronchial wall, chronic inflammation, and destruction of affected bronchi. Underlying etiologies include severe pulmonary infection and cystic fibrosis (CF); however, in a substantial number of patients with non-CF-related bronchiectasis (NCFB), no cause is found. The increasing armamentarium of therapies now available to combat disease in CF is in stark contrast to the limited tools employed in NCFB. Our study aimed to evaluate similarities and differences in airway inflammatory markers in patients with NCFB and CF, and to suggest potential common treatment options. The results of this study show that NCFB bronchoalveolar lavage fluid samples possessed significantly increased NE activity and elevated levels of matrix metalloproteinases 2 (MMP-2) and MMP-9 compared to healthy controls (P , 0.01); however, the levels detected were lower than in CF (P , 0.01). Interleukin-8 (IL-8) concentrations were significantly elevated in NCFB and CF compared to controls (P , 0.05), but in contrast, negligible levels of IL-18 were detected in both NCFB and CF. Analogous concentrations of IL-10 and IL-4 measured in NCFB and CF were statistically elevated above the healthy control values (P , 0.05 and P , 0.01, respectively). These results indicate high levels of important proinflammatory markers in both NCFB and CF and support the use of appropriate anti-inflammatory therapies already employed in the treatment of CF bronchiectasis in NCFB.
The Role of Inflammation in the Pathophysiology of CF Lung Disease
Clinical Reviews in Allergy & Immunology, 2002
Cystic fibrosis (CF) lung disease is characterized by a self-perpetuating cycle of airway obstruction, chronic bacterial infection, and vigorous inflammation that results in structural damage to the airway. CF patients have a predilection for infection with a limited spectrum of distinctive bacteria that initiate a vigorous inflammatory response which is more harmful than protective. The airway epithelial cell, which normally expresses the cystic fibrosis transmembrane conductance regulator (CFTR), directs the inflammatory response. Defects in CFTR are associated with increased production of proinflammatory mediators including IL-8, a potent neutrophil chemoattractant that stimulates the influx of massive numbers of neutrophils into the airways. These neutrophils are the primary effector cells responsible for the pathological manifestations of CF lung disease. Documented deficiencies in immunoregulatory molecules such as IL-10 likely contribute to the generation of the excessive and persistent inflammatory response. Since inflammation is a key contributor to the pathogenesis of CF lung disease, anti-inflammatory therapy must assume a larger role in CF until a cure is discovered. To date, attention has focused primarily on the therapeutic potential of systemic and inhaled corticosteroids and the non-steroidal antiinflammatory drug (NSAID) ibuprofen. Development of new anti-inflammatory therapies that impact intracellular signaling pathways and cell-cell communication molecules likely will have the greatest impact on limiting 5
Increased Leukotriene B 4 and Interleukin-6 in Exhaled Breath Condensate in Cystic Fibrosis
American Journal of Respiratory and Critical Care Medicine, 2003
Chronic neutrophilic airway inflammation is an important feature The persistent inflammation in the airways of patients of cystic fibrosis (CF). Noninvasive inflammatory markers may be with CF may also be due to cytokines generated by bacterial useful in monitoring CF. Leukotriene B 4 (LTB 4) and interleukin (IL)-6 infection, oxidative stress, or constitutive abnormalities in are inflammatory mediators that are increased in chronic neutrothe regulation of cytokine production (8). Inflammatory cytophilic inflammation. The aim of this study was to assess whether kines may play an important role in amplification of inflam-LTB 4 and IL-6 were increased in exhaled breath condensate of CF mation and tissue damage in the lung of patients with CF. patients and whether they could be used to monitor inflammation. Interleukin (IL)-6 is a cytokine that has both inflammatory Twenty patients with CF (13 males, age of 28 Ϯ 9 years) were and anti-inflammatory actions. It regulates production of recruited together with 15 age-matched healthy subjects (8 males, acute phase protein, which may locally limit the actions of age 35 Ϯ 7 years). LTB 4 and IL-6 levels were markedly elevated in inflammatory cells (9). IL-6 provides a negative feedback patients with acute exacerbations (28.8 Ϯ 4.3 and 8.7 Ϯ 0.4 pg/ml) signal by downregulating tumor necrosis factor-␣, which is compared with control subjects (6.8 Ϯ 0.7 and 2.6 Ϯ 0.1 pg/ml, p Ͻ a potent mediator of inflammation and is the first cytokine 0.0001). We also observed a decrease of exhaled LTB 4 and IL-6 to be released after interaction of host cells with a variety concentrations after antibiotic treatment in six patients who were of microbial products (10). IL-6 also enhances secretion of followed until clinically stable (31.1 Ϯ 4.4 and 9.5 Ϯ 0.4 pg/ml vs. 18.8 Ϯ 0.8 and 6.4 Ϯ 0.2 pg/ml, respectively) and an increase in antibodies from B-lymphocytes, hyperglobulinemia, and lo-15 CF patients infected with Pseudomonas aeruginosa (34.3 Ϯ 5.0 cal immune complex deposition (9). and 9.3 Ϯ 0.3 pg/m) compared with those infected with other Monitoring of airways inflammation may be important in bacteria (18.3 Ϯ 0.7 and 6.9 Ϯ 0.5 pg/ml). These findings suggest patients with CF, as airways disease is the predominant cause that LTB 4 and IL-6 levels are increased in exhaled breath condensate of death in CF (11). Noninvasive inflammatory markers may of patients with CF during exacerbation and could be used to monibe therefore useful in monitoring disease activity and protor airway inflammation in these patients. gression (12). There is a need to find potential new markers of inflammation, which could help in early diagnosis or pre-Keywords: leukotriene B 4 ; interleukin-6, cystic fibrosis; exhaled breath diction of disease exacerbations so that early administration condensate; airway inflammation
Exhaled nitric oxide is not reduced in infants with cystic fibrosis
European Respiratory Journal, 2006
Fractional exhaled nitric oxide (FeNO) has been reported to be reduced in cystic fibrosis (CF) patients. However, data from young children are conflicting and it is not clear whether this is a primary feature of the disease or a secondary response. The present study compared FeNO between CF and healthy infants using a validated single-breath technique.