Determinants of induced sputum neutrophil differential count in healthy children: role of interleukin-8 and oxidative stress

In healthy children, there is a wide range in the induced sputum neutrophil differential count. To date, the reason for this is unclear. In animal models, neutrophil chemoattractant cytokines and oxidative stress are major determinants of airway neutrophilia. In this study, we therefore aimed to assess the association between interleukin-8, and the oxidative stress marker 8-oxo-7, 8-dihydro-2’-deoxyguanosine (8-oxodG), with the neutrophil count in induced sputum samples from healthy children

Carbon in airway macrophages and lung function in children

BACKGROUND: Epidemiologic studies indirectly suggest that the inhalation of carbonaceous particulate matter impairs lung function in children. Using the carbon content of airway macrophages as a marker of individual exposure to particulate matter derived from fossil fuel, we sought direct evidence of this association. METHODS: Airway macrophages were obtained from healthy children through sputum induction, and the area of airway macrophages occupied by carbon was measured. Lung function was measured with the use of spirometry. We modeled the exposure to primary particulate matter (PM) that is less than 10 mum in aerodynamic diameter (PM10) at or near each child's home address. Linear regression was used to evaluate associations between carbon content of alveolar macrophages and variables that may affect individual exposure. To determine whether lung function that is reduced for other reasons is associated with an increase in the carbon content of airway macrophages, we also studied children with severe asthma. RESULTS: We were able to assess the carbon content of airway macrophages in 64 of 114 healthy children (56 percent). Each increase in primary PM10 of 1.0 microg per cubic meter was associated with an increase of 0.10 microm2 (95 percent confidence interval, 0.01 to 0.18) in the carbon content of airway macrophages, and each increase of 1.0 microm2 in carbon content was associated with a reduction of 17 percent (95 percent confidence interval, 5.6 to 28.4 percent) in forced expiratory volume in one second, of 12.9 percent (95 percent confidence interval, 0.9 to 24.8 percent) in forced vital capacity, and of 34.7 percent (95 percent confidence interval, 11.3 to 58.1 percent) in the forced expiratory flow between 25 and 75 percent of the forced vital capacity. The carbon content of airway macrophages was lower in children with asthma than in healthy children. CONCLUSIONS: There is a dose-dependent inverse association between the carbon content of airway macrophages and lung function in children. We found no evidence that reduced lung function itself causes an increase in carbon content

Ciliated conical epithelial cell protrusions point towards a diagnosis of primary ciliary dyskinesia

BACKGROUND: Primary ciliary dyskinesia can result from a number of different ciliary defects that adversely affect ciliary function resulting markedly reduced or absent mucociliary clearance. Improvement in diagnostic testing is an area of current research. During diagnostic evaluation of PCD we observed ciliated conical protrusions from part of the apical surface of ciliated cells in those diagnosed with PCD. The aim of this study was to investigate if this abnormality was specific to PCD. METHODS: Epithelial edges from 67 consecutively diagnosed PCD patients, 67 patients consecutively referred for PCD diagnostic testing in whom PCD was excluded, 22 with asthma and 18 with Cystic Fibrosis (CF) were studied retrospectively in a blinded manner using light microscopy. RESULTS: Forty six out of 67 patients with PCD had ciliated conical epithelial protrusions, whereas none were seen in patients where PCD was excluded, or in patients with asthma or CF. The sensitivity, specificity, positive predictive value and negative predictive value for the presence of the ciliated conical protrusions to predict a diagnosis of PCD were 76.5, 100, 100 and 77% respectively. CONCLUSIONS: Characteristic ciliated conical protrusions from ciliated epithelial cells maybe a useful pointer to the diagnosis of PCD. However, their absence does not exclude the diagnosis of PCD

Additional file 2: of Ciliated conical epithelial cell protrusions point towards a diagnosis of primary ciliary dyskinesia

Sensitivity calculation. (DOCX 147 kb

COPD exacerbation severity and frequency is associated with impaired macrophage efferocytosis of eosinophils

Background: Eosinophilic airway inflammation is observed in 10-30% of COPD subjects. Whether increased eosinophils or impairment in their clearance by macrophages is associated with the severity and frequency of exacerbations is unknown. Methods: We categorised 103 COPD subjects into 4 groups determined by the upper limit of normal for their cytoplasmic macrophage red hue (<6%), an indirect measure of macrophage efferocytosis of eosinophils, and area under the curve sputum eosinophil count (≥3%/year). Eosinophil efferocytosis by monocyte-derived macrophages was studied in 17 COPD subjects and 8 normal controls. Results: There were no differences in baseline lung function, health status or exacerbation frequency between the groups: A-low red hue, high sputum eosinophils (n = 10), B-high red hue, high sputum eosinophils (n = 16), C-low red hue, low sputum eosinophils (n = 19) and D- high red hue, low sputum eosinophils (n = 58). Positive bacterial culture was lower in groups A (10%) and B (6%) compared to C (44%) and D (21%) (p = 0.01). The fall in FEV1 from stable to exacerbation was greatest in group A (ΔFEV1 [95 % CI] -0.41 L [-0.65 to -0.17]) versus group B (-0.16 L [-0.32 to -0.011]), C (-0.11 L [-0.23 to -0.002]) and D (-0.16 L [-0.22 to -0.10]; p = 0.02). Macrophage efferocytosis of eosinophils was impaired in COPD versus controls (86 [75 to 92]% versus 93 [88 to 96]%; p = 0.028); was most marked in group A (71 [70 to 84]%; p = 0.0295) and was inversely correlated with exacerbation frequency (r = -0.63; p = 0.006). Conclusions: Macrophage efferocytosis of eosinophils is impaired in COPD and is related to the severity and frequency of COPD exacerbations

Monitoring asthma in childhood: management-related issues.

Management-related issues are an important aspect of monitoring asthma in children in clinical practice. This review summarises the literature on practical aspects of monitoring including adherence to treatment, inhalation technique, ongoing exposure to allergens and irritants, comorbid conditions and side-effects of treatment, as agreed by the European Respiratory Society Task Force on Monitoring Asthma in Childhood. The evidence indicates that it is important to discuss adherence to treatment in a non-confrontational way at every clinic visit, and take into account a patient's illness and medication beliefs. All task force members teach inhalation techniques at least twice when introducing a new inhalation device and then at least annually. Exposure to second-hand tobacco smoke, combustion-derived air pollutants, house dust mites, fungal spores, pollens and pet dander deserve regular attention during follow-up according to most task force members. In addition, allergic rhinitis should be considered as a cause for poor asthma control. Task force members do not screen for gastro-oesophageal reflux and food allergy. Height and weight are generally measured at least annually to identify individuals who are susceptible to adrenal suppression and to calculate body mass index, even though causality between obesity and asthma has not been established. In cases of poor asthma control, before stepping up treatment the above aspects of monitoring deserve closer attention