Silvia Carraro

Cysteinyl leukotrienes and 8-isoprostane in exhaled breath condensate of children with asthma exacerbations

Background: Cysteinyl leukotrienes (Cys-LTs) and isoprostanes are inflammatory metabolites derived from arachidonic acid whose levels are increased in the airways of asthmatic patients. Isoprostanes are relatively stable and specific for lipid peroxidation, which makes them potentially reliable biomarkers for oxidative stress. A study was undertaken to evaluate the effect of a course of oral steroids on Cys-LT and 8-isoprostane levels in exhaled breath condensate of children with an asthma exacerbation. Methods: Exhaled breath condensate was collected and fractional exhaled nitric oxide (FENO) and spirometric parameters were measured before and after a 5 day course of oral prednisone (1 mg/kg/day) in 15 asthmatic children with an asthma exacerbation. Cys-LT and 8-isoprostane concentrations were measured using an enzyme immunoassay. FENO was measured using a chemiluminescence analyser. Exhaled breath condensate was also collected from 10 healthy children. Results: Before prednisone treatment both Cys-LT and 8-isoprostane concentrations were higher in asthmatic subjects (Cys-LTs, 12.7 pg/ml (IQR 5.4–15.6); 8-isoprostane, 12.0 pg/ml (9.4–29.5)) than in healthy children (Cys-LTs, 4.3 pg/ml (2.0–5.7), p=0.002; 8-isoprostane, 2.6 pg/ml (2.1–3.0), p<0.001). After prednisone treatment there was a significant decrease in both Cys-LT (5.2 pg/ml (3.9–8.8), p=0.005) and 8-isoprostane (8.4 pg/ml (5.4–11.6), p=0.04) concentrations, but 8-isoprostane levels remained higher than in controls (p<0.001). FENO levels, which fell significantly after prednisone treatment (p<0.001), did not correlate significantly with either Cys-LT or 8-isoprostane concentrations. Conclusion: After a 5 day course of oral prednisone there is a reduction in Cys-LT and 8-isoprostane levels in EBC of children with an asthma exacerbation, although 8-isoprostane levels remain higher than in controls. This finding suggests that corticosteroids may not be fully effective in reducing oxidative stress in children with an exacerbation of asthma.

Daily Telemonitoring of Exhaled Nitric Oxide and Symptoms in the Treatment of Childhood Asthma

RATIONALE Asthma treatment might improve when inhaled steroids are titrated on airway inflammation. Fractional exhaled nitric oxide (FeNO0.05), a marker of eosinophilic airway inflammation, can be measured at home. OBJECTIVES We assessed daily FeNO0.05 telemonitoring in the management of childhood asthma. METHODS Children with atopic asthma (n = 151) were randomly assigned to two groups: FeNO0.05 plus symptom monitoring, or monitoring of symptoms only. All patients scored asthma symptoms in an electronic diary over 30 weeks; 77 received a portable nitric oxide (NO) analyzer. Data were transmitted daily to the coordinating centers. Patients were phoned every 3 weeks and their steroid dose was adapted according to FeNO0.05 and symptoms, or according to symptoms. Children were seen at 3, 12, 21, and 30 weeks for examination and lung function testing. The primary end point was the proportion of symptom-free days in the last 12 study weeks. MEASUREMENTS AND MAIN RESULTS Telemonitoring was feasible with reliable FeNO0.05 data for 86% of days, and valid diary entries for 79% of days. Both groups showed an increase in symptom-free days, improvement of FEV1 and quality of life, and a reduction in steroid dose. None of the changes from baseline differed between groups. The difference in symptom-free days over the last 12 weeks was 0.3% (P = 0.95; 95% confidence interval, -10 to 11%). There was a trend for fewer exacerbations in the FeNO0.05 group. CONCLUSIONS Thirty weeks of daily FeNO0.05 and symptom telemonitoring was associated with improved asthma control and a lower steroid dose. We found no added value of daily FeNO0.05 monitoring compared with daily symptom monitoring only.

Asthma, allergy and respiratory infections: the vitamin D hypothesis

To cite this article: Bozzetto S, Carraro S, Giordano G, Boner A, Baraldi E. Asthma, allergy, and respiratory infections: the vitamin D hypothesis. Allergy 2012; 67: 10–17.

Safety and success of exhaled breath condensate collection in asthma

Background: Exhaled breath condensate (EBC) is a rapidly expanding area of research to study airway inflammation through the detection of volatile and non-volatile substances in the airways. Aims: To determine the safety and feasibility of EBC procedure in a group of children with asthma of varying severity. Methods: In a cross sectional study of children aged 4–17 years, 18 healthy and 91 asthmatic children (69 in stable condition and 22 with asthma exacerbation) underwent the EBC procedure. Outcomes assessed included completion of the procedure, decrease in FEV1, change in fractional exhaled nitric oxide (FENO), and adverse effects. No pretreatment with β2 agonists was given. All children were able to successfully complete the EBC procedure. Results: Median fall in FEV1 after the procedure was −1% (IQR −3.5, 1.8) in asthmatics and was comparable to that observed in healthy children. In only one asthmatic child did the drop in FEV1 exceed 12%. No significant changes in FENO were observed after EBC. Conclusion: This study suggests that EBC is a simple and well tolerated method for evaluating biological samples from the lower airway. The procedure was safe in children with asthma exacerbation, and the success rate was 100% in children aged 4 years and above.

Acid-base equilibrium in exhaled breath condensate of allergic asthmatic children.

Background:  The dysregulation of airway pH control may have a role in asthma pathophysiology. The measurement of exhaled breath condensate (EBC) pH and ammonia levels may be used as a noninvasive method to study acid–base status in the airway of asthmatics.

Asthma severity in childhood and metabolomic profiling of breath condensate

Asthma is a heterogeneous disease and its different phenotypes need to be better characterized from a biochemical‐inflammatory standpoint. This study aimed to apply the metabolomic approach to exhaled breath condensate (breathomics) to discriminate different asthma phenotypes, with a particular focus on severe asthma in children.

3-Nitrotyrosine, a marker of nitrosative stress, is increased in breath condensate of allergic asthmatic children.

Background:  Asthmatic patients have high exhaled nitric oxide (NO) levels. NO‐mediated inflammatory actions are mainly due to NO conversion into reactive nitrogen species, which can lead to nitrotyrosine formation. The aim of this study was to assess 3‐nitrotyrosine (3‐NT) levels in exhaled breath condensate (EBC) of asthmatic and healthy children and to investigate whether there is any relationship with exhaled NO (FENO) and lung function.

Childhood Course of Lung Function in Survivors of Bronchopulmonary Dysplasia

refinement. However, we remain committed to the continual refinement of explicit algorithms because they are the best means of achieving and sustaining long-term gains in performance. Implicit algorithms are the mental models an individual uses to select his or her response to a given situation. Although experience allows the individual to refine these models, that knowledge remains internal and will be lost when the individual dies. Consequently, long-term progress depends on converting that implicit knowledge into explicit algorithms so that they may be further refined by other individuals. This conversion and subsequent communication is the basis of organizational learning. Mentioning explicit algorithms frequently generates a visceral reaction since many people may consider such algorithms to be unduly confining. However, the only available alternative is implicit algorithms; since these will vary from individual to individual, it is exceedingly unlikely that a system built on implicit algorithms will produce a reliable result. We agree that complex problems can rarely be reduced to a single solution or target point. However, the limitations of human information processing, particularly the limited capacity of working memory, necessitate representing solutions as target points or as narrowly defined solution spaces. Even if the chosen target differs from the ideal, reductions in variation provide 2 benefits. First, minimal variation provides assurance that the process is tightly controlled. Second, any difference between the observed and desired result is less likely to be obscured by noise. We also agree that variation, whether due to nuanced observations, subjective hunches, or chance events, can lead to future improvement. Genetic variation provides a useful example. Most mutations are deleterious, but a small percentage are beneficial. The key is to create feedback loops that continually interpret results, recognize the benefit, refine the algorithm to leverage the benefit, and report the result so that others may build on the knowledge gained. We agree with the majority of Wilkinson’s observations. The remaining differences are likely best attributed to the difficulty of communicating ideas such as the benefits of explicit over implicit algorithms and how variation can be considered a 2-edged sword.

Fluctuation phenotyping based on daily fraction of exhaled nitric oxide values in asthmatic children

BACKGROUND Fraction of exhaled nitric oxide (Feno), a marker of airway inflammation, has been proposed to be useful for asthma management, but conclusions are inconsistent. This might be due to the failure of mean statistics to characterize individual variability in Feno values, which is possibly a better indicator of asthma control than single measurements. OBJECTIVE We characterized fractal fluctuations in daily Feno values over time and the relationship between Feno values and symptom scores. We investigated whether these are associated with asthma severity, control, and exacerbation risk. METHODS Daily Feno values and symptom scores over 192 days in 41 atopic asthmatic children from the Childhood Asthma Respiratory Inflammatory Status Monitoring study were analyzed. Two methods of time-series analysis were used: detrended fluctuation analysis to quantify fractal patterns in fluctuations in daily Feno values (α value) and cross-correlation to quantify the strength of the relationship between daily Feno values and symptom scores. The associations of α values and cross-correlation with markers of asthma severity and control were assessed by means of regression analysis. RESULTS Daily fluctuations in Feno values exhibited fractal-type long-range correlations. Those subjects receiving higher doses of inhaled corticosteroids at study entry had a significantly lower α value, corresponding to more random fluctuations in Feno values in those with greater inhaled corticosteroid need. The cross-correlation between Feno values and symptom scores was significantly higher in those subjects who had exacerbations. CONCLUSIONS Fluctuation in Feno values and their cross-correlation to symptom scores contains information on asthma severity and control. Methods that quantify the complexity of asthma over time might assist in identifying asthmatic subjects with concordance between eosinophilic inflammation and symptoms and thus increased exacerbation risk.

Swimming pool, respiratory health, and childhood asthma: should we change our beliefs?

Swimming is often recommended as a sport because of its several benefits to health. It is also recommended in asthmatic children as a sport with a lower potential for prompting exercise‐induced asthma. However, there is growing interest in the potentially harmful effects of repeated respiratory tract exposure to chlorinated products and the problem of possible swimming‐related health hazards is gaining importance at international level. It is already known that acute exposure to chlorine gas as in swimming pool accidents causes lung damage and also that elite swimmers may have increased airway inflammation and bronchial hyperreactivity, probably as a result of repeated exposure to chlorine derivatives. Recently some studies have been conducted to investigate whether repeated exposure to chlorine by‐products in recreational swimmers might also lead to lung damage. In addition, some studies have been lately published on the even more debated issue of the possible harmful effects of baby swimming on respiratory health. This article reviews and discusses data from the literature on the effects of chlorine derivatives in different categories of people routinely attending swimming pools. The need for longitudinal studies is emphasized to definitely clarify any role of chlorinated swimming pool attendance in the development of asthma in recreational swimmers. Pediatr Pulmonol. 2009; 44:31–37.