Isoprostane-8 in the exhaled breath condensate: Could it represent a noninvasive strategic tool for primary ciliary dyskinesia diagnosis and management?

BACKGROUND AND OBJECTIVES: Exhaled breath condensate (EBC) represents a potential diagnostic tool for Primary Ciliary Diskinesia (PCD). An increased oxidative stress is present in the airways of children affected and many neutrophil chemoattractants and markers of oxidative stress can be involved. The aim of the study is to evaluate leukotriene B4 (LTB-4), interleukin 8 (IL-8), 8-isoprostane (8-IP) concentration in PCD subjects, investigating their potential role as non-invasive markers of inflammation for the diagnosis and management of PCD. METHODS: Cross-sectional study. 43 patients were enrolled in the study and divided in two groups: PCD (27) and healthy subjects (16). Physical examination, lung function test, nFeNO measurement and EBC collection were performed in all subjects. RESULTS: PCD subjects showed an EBC 8-IP concentration significantly higher than the control group (median value: 11.9 pg/ml; IQR, 5.5-24.0 vs. median, 6.7 pg/ml; IQR, 2.5-11.3, p-value of Wilcoxon rank-sum test 0.0436). LTB4 EBC concentration did not differ between the two group (median, 4.3 pg/ml; IQR, 3.0-8.8 vs. 7.5 pg/ml; IQR, 3.0-9.5; P=0.4901). No significant correlation was found between FEV1 and EBC 8-IP (r=-0.10, P=0.6314) or LTB4 concentration (r=0.03, P=0.8888) in PCD subjects. No significant correlation was found between nFeNO and EBC 8-IP (r=-0.31, P=0.1385) or LTB4 (r=0.04, P=0.8565) in PCD subjects. CONCLUSIONS: EBC 8-IP levels are significantly increased in PCD subjects, highlighting the role of oxidative stress in airway inflammation. It could have a potential role as a non-invasive marker of inflammation for the diagnosis and management of PCD, although a therapeutic application of this evidence seems far.

Airways flat angioma misdiagnosed as difficult asthma in an adolescent.

A 15 years-old boy came to our attention with a diagnosis of poorly controlled asthma. This case required thorough investigations: CT scan imaging revealed a flat angioma extending from the carina to the left main bronchus. Rigid bronchoscopy confirmed the presence of an angioma showing widespread mucosal diffusion involving most of the posterior tracheal wall and main bronchi, on the left side. We present this case report and these images to readers seeking for other experiences in the diagnosis of wide superficial bronchial angioma in pediatric age.

Can inhaled foreign body mimic asthma in an adolescent?

A 14 year old male was diagnosed with asthma but didn't improve with appropriate inhalation therapy. Rigid bronchoscopy revealed a food fragment, almost completely occluding the lower-left bronchus lumen. Based on the reported history, it had been likely there for several years.

Structured Light Plethysmography (SLP): Management and follow up of a paediatric patient with pneumonia.

Structured Light Plethysmography (SLP) is a non-invasive method to study chest and abdominal movement during breathing and can identify abnormal contributions of the different regions of the chest. M.D hospitalized for pneumonia, underwent SLP and spirometry at admission (T0), after 48 hours (T1), and after one month (T2). SLP parameters showed expiratory flow limitation, information consistent with the spirometric parameters collected, and reduced motion in the area effected by pneumonia, with improvement and normalization at T1 and T2. This method gave useful information about the contribution to the respiratory movement of the lung area affected by pneumonia so we can speculate a possible use in the follow-up of children affected by pneumonia or other respiratory diseases, and who are not able to perform a spirometric test.

Antioxidant supplementation and exhaled nitric oxide in children with asthma.

BACKGROUND: The effect of allergen avoidance on airway inflammation is similar to that observed with treatment with inhaled steroids, whereas inhaled steroids have no effect on oxidative stress-induced inflammation. OBJECTIVE: The aim of this study was to retrospectively evaluate the potential effect of an antioxidant dietary supplement on exhaled nitric oxide over a month in pediatric patients on stable antiasthma treatment. METHODS: Forty-seven children with moderate-to-severe asthma were retrospectively evaluated. All the patients were sensitive to Dermatophagoides pteronyssinus and Dermatophagoides farinae, and they were receiving the minimum inhaled corticosteroid dosage required to maintain adequate control. Within a few weeks of admission at Misurina Hospital in the Alps, the regular treatment was gradually reduced, then some children who were receiving a daily dose of inhaled corticosteroids, ≤200 mcg of fluticasone propionate, were prescribed a nutraceutical dietary supplement for at least 4 weeks. Lung function and fractional exhaled nitric oxide (FeNO) measurements were recorded at the beginning and after 1 month of the dietary supplementation. RESULTS: Baseline lung function and FeNO values did not differ between the two groups of patients. After 4 weeks of nutraceutical supplementation, FeNO values decreased, from 19.00 ppb (interquartile range, 14-31 ppb) to 11.00 ppb (interquartile range, 6-23 ppb) (p = 0.03). No significant reduction was observed in the group that did not receive the supplementation, and no significant difference between groups was observed, both at baseline and after 4 weeks of nutraceutical supplementation. CONCLUSION: Supplementation with a nutraceutical of antioxidants and anti-inflammatory compounds, such as curcumin, resveratrol, soy phospholipids, zinc, selenium, and vitamin D, may be associated with reduced airway inflammation, as documented by a fall in FeNO.

Streptococcus pneumoniae colonisation in children and adolescents with asthma: impact of the heptavalent pneumococcal conjugate vaccine and evaluation of potential effect of thirteen-valent pneumococcal conjugate vaccine.

BACKGROUND: The main aim of this study was to evaluate Streptococcus pneumoniae carriage in a group of school-aged children and adolescents with asthma because these results might indicate the theoretical risk of invasive pneumococcal disease (IPD) of such patients and the potential protective efficacy of the 13-valent pneumococcal conjugate vaccine (PCV13). METHODS: Oropharyngeal samples were obtained from 423 children with documented asthma (300 males, 70.9%), and tested for the autolysin-A-encoding (lytA) and the wzg (cpsA) gene of S. pneumoniae by means of real-time polymerase chain reaction. RESULTS: S. pneumoniae was identified in the swabs of 192 subjects (45.4%): 48.4% of whom were aged <10 years, 46.9% aged 10-14 years, and 4.7% aged ≥15 years (p < 0.001). Carriage was significantly less frequent among the children who had received recent antibiotic therapy (odds ratio [OR 0.41]; 95% confidence interval [95% CI] 0.22-0.76). Multivariate analyses showed no association between carriage and vaccination status, with ORs of 1.05 (95% CI 0.70-1.58) for carriers of any pneumococcal serotype, 1.08 (95% CI 0.72-1.62) for carriers of any of the serotypes included in 7-valent pneumococcal conjugate vaccine (PCV7), and 0.76 (95% CI 0.45-1.28) for carriers of any of the six additional serotypes of PCV13. Serotypes 19 F, 4 and 9 V were the most frequently identified serotypes in vaccinated subjects. CONCLUSIONS: These results showed that carriage of S. pneumoniae is relatively common in all school-aged children and adolescents with asthma, regardless of the severity of disease and the administration of PCV7 in the first years of life. This highlights the problem of the duration of the protection against colonisation provided by pneumococcal conjugate vaccine, and the importance of re-colonization by the same pneumococcal serotypes included in the previously used vaccine.

Exhaled breath temperature and exercise-induced bronchoconstriction in asthmatic children.

It has been hypothesized that exhaled breath temperature (EBT) is related to the degree of airway inflammation/remodeling in asthma. The purpose of this study was to evaluate the relationship between the level of airway response to exercise and EBT in a group of controlled or partly controlled asthmatic children. Fifty asthmatic children underwent measurements of EBT before and after a standardized exercise test. EBT was 32.92 ± 1.13 and 33.35 ± 0.95°C before and after exercise, respectively (P < 0.001). The % decrease in FEV(1) was significantly correlated with the increase in EBT (r = 0.44, P = 0.0013), being r = 0.49 (P < 0.005) in the children who were not receiving regular inhaled corticosteroids (ICS) and 0.37 (n.s.) in those who were. This study further supports the hypothesis that EBT can be considered a potential composite tool for monitoring asthma.

Monitoring asthma control in children with allergies by soft computing of lung function and exhaled nitric oxide.

BACKGROUND: Asthma control is emphasized by new guidelines but remains poor in many children. Evaluation of control relies on subjective patient recall and may be overestimated by health-care professionals. This study assessed the value of spirometry and fractional exhaled nitric oxide (FeNO) measurements, used alone or in combination, in models developed by a machine learning approach in the objective classification of asthma control according to Global Initiative for Asthma guidelines and tested the model in a second group of children with asthma. METHODS: Fifty-three children with persistent atopic asthma underwent two to six evaluations of asthma control, including spirometry and FeNO. Soft computing evaluation was performed by means of artificial neural networks and principal component analysis. The model was then tested in a cross-sectional study in an additional 77 children with allergic asthma. RESULTS: The machine learning method was not able to distinguish different levels of control using either spirometry or FeNO values alone. However, their use in combination modeled by soft computing was able to discriminate levels of asthma control. In particular, the model is able to recognize all children with uncontrolled asthma and correctly identify 99.0% of children with totally controlled asthma. In the cross-sectional study, the model prospectively identified correctly all the uncontrolled children and 79.6% of the controlled children. CONCLUSIONS: Soft computing analysis of spirometry and FeNO allows objective categorization of asthma control status.

Chronic urticaria and celiac disease: a case report.

We describe a case of a 9-year-old girl who presented chronic urticaria associated with celiac disease. The prevalence of the manifestation of chronic urticaria in celiac disease is unknown but increase in atopic immunologic disorders has been reported in the setting of gluten enteropathy. Relationship between the clinical manifestations is not clear. The present case of subclinical celiac disease diagnosis in an otherwise asymptomatic child with chronic urticaria further reinforces the evidence that differential for celiac disease warrants to be always considered in children with refractory urticaria.

Atypical bacteria in adenoids and tonsils of children requiring adenotonsillectomy.

CONCLUSIONS: The results of this study suggest that atypical bacteria may be involved not only in acute upper airway diseases but also in recurrent infections requiring adenoidectomy and/or tonsillectomy. Therefore, their identification, followed by an appropriate treatment, should be considered. OBJECTIVE: Although viruses and group A beta-haemolytic streptococci (GABHS) represent the most frequent bacterial aetiological agents of paediatric upper respiratory tract infections (URTIs), chlamydia and Mycoplasma pneumoniae have also been found in acute tonsillopharyngitis. Nevertheless their relevance in chronic or recurrent URTI has never been evaluated. This study aimed to further address the role of atypical bacteria in recurrent URTIs requiring adenoidectomy and tonsillectomy. METHODS: Samples from 55 consecutive children who underwent adenoidectomy and/or tonsillectomy for recurrent or chronic URTI were cut transversely into smaller sections of 5 mm. Each section was pooled and assayed by specific PCR for viruses and bacteria. RESULTS: Adenovirus was detected in 10 patients (18.2%), influenza A virus in one patient and influenza B virus in another. None of the other tested viruses was found. GABHS was found in 37 patients (67.3%). Moraxella catarrhalis and Haemophilus influenzae were detected in 30 patients (54.5%). M. pneumoniae was detected in 6 patients (10.9%) and C. pneumoniae was found in 10 patients (18.2%).

Transforming growth factor-beta is elevated in unpasteurized cow's milk.

Unpasteurized milk consumption was associated with less atopy prevalence. Not only microbial load but also fatty acids and cytokines such as transforming growth factor-beta(1) (TGF-beta(1)) may play a role on the effect of unpasteurized milk. Levels of TGF-beta(1) in different cow's milk samples were evaluated: we consider raw unpasteurized milk before and after boiling, commercial pasteurized and micro-filtrated cow's milk and different commercially available cow's milk formulas. TGF-beta(1) concentration in raw unpasteurized cow's milk was 642.0 +/- 52.9 pg/ml before boiling and decreased significantly after boiling (302.7 +/- 50.59 pg/ml) (p < 0.05). TGF-beta(1) concentrations were also significantly lower in commercial pasteurized milk (246.2 +/- 43.15 pg/ml) and in commercial micro-filtrated milk (213.0 +/- 31.6 pg/ml) in comparison to unpasteurized unboiled milk (p = 0.002). The levels of TGF-beta(1) in all formula samples were below the threshold of detectability for the assays. As TGF-beta(1) in the milk may contribute to the development of the immature gastrointestinal tract by influencing IgA production and oral tolerance induction, we suggest to consider not only the microbial compounds but also the cytokine patterns to explain the protective effect of unpasteurized cow's milk on allergic disorders.

Cow's milk allergic children can present sensitisation to probiotics.

AIM: To evaluate sensitivity to different probiotics in children with cow's milk allergy. METHODS: Eighty-five patients (age range: 4 months -12 years) presenting atopic dermatitis (AD) were enrolled. Skin prick test (SPT) responses to three different probiotics preparations (Fiorilac, Dicoflor and Reuterin) were evaluated in addition to relevant food allergens. RESULTS: Thirty-nine patients out of 85 (45.8%) had a positive skin response to prick test for cow's milk (3 with reaction <3 mm). Of the thirty-six patients with a cow's milk weal reaction >3 mm, twenty-eight (77.8%) had a skin response to Fiorilac, four patients (11%) to Dicoflor and four (11%) to Reuterin. The proportion of SPT reaction to all the investigated probiotics preparations was significantly lower than cow's milk (r = 9.406; p = 0.002). A significantly higher sensitization was observed for Fiorilac versus Dicoflor (r = 30.916; p < 0.001) and versus Reuterin (r = 34.133; p < 0.001). CONCLUSION: Probiotic use in patients with cow's milk allergy has to be limited to products that do not contain milk. This should be clearly reported in the label. In selected patients, it is advisable to perform a screening SPT with the product to evaluate its potential contamination with milk.

Preschool asthma in Italy: prevalence, risk factors and health resource utilization.

Asthma in preschool children is greatly under-diagnosed worldwide. Aim was to investigate prevalence of wheezing, and asthma risk factors, doctor diagnosis, treatment and health resource utilization in preschool children. About 1402 children (3-5 years) attending local kindergartens participated in the study. The International Study of Asthma and Allergies in Childhood (ISAAC) written questionnaire (WQ) was used with additional questions on risk factors, asthma diagnosis, treatments, resource utilization. Allergic sensitisation was evaluated by skin prick tests for the common allergens. Prevalence of "wheezing in previous 12 months" and "doctor diagnosed asthma" were 12.1% and 8.6%, respectively. 4.7% of children have had both wheezing in the last 12 months and asthma diagnosis. Significant risk factors for wheezing were rhinitis, parental history of atopy and sensitivity to mites and grass pollens. 27.3% of children with asthma diagnosis, but only 4.9% of children without diagnosis, received regular treatment during the previous year (p<0.0001). Children with more than 4 episodes of wheezing a year received more frequently an asthma diagnosis, but 68.6% were not on regular treatment. Asthma diagnosis was associated with a significant increase in control visits for wheezing (p<0.0001). The prevalence of children requiring at least one hospital emergency visit in the previous year was not different among the two groups (83.3% vs. 82.5%). In preschool children the prevalence of wheezing and asthma is elevated. Preschool asthma seems to be under-treated with few cases receiving regular therapy. The social cost of the disease at this age seems to be elevated because of the high frequency of control and emergency visits.

Nasal nitric oxide for early diagnosis of primary ciliary dyskinesia: practical issues in children.

BACKGROUND: Primary ciliary dyskinesia (PCD) is a genetic disease characterized by abnormally beating cilia. In these patients, levels of nasal nitric oxide (nNO) are lower than those observed in healthy subjects. OBJECTIVES: We identify the nNO levels in healthy pre-school uncooperative children and in PCD patients, in order the application of nNO measurement in the early identification of young children with PCD. METHODS: We measured nNO in 77 healthy children (50 uncooperative and 27 cooperative) and in 10 PCD patients. Fifteen cooperative healthy children were also asked to perform an uncooperative test. RESULTS: PCD patients presented low nNO levels (29.7+/-5.7 ppb) compared to those observed in healthy children (358.8+/-35.2 ppb; p<0.05). nNO levels were increased in healthy cooperative children (650+/-60.6 ppb; p<0.05) as compared to those uncooperative aging more than 6 month (309.1+/-45.9 ppb; p<0.05) or less (128.1+/-16.2 ppb; p<0.05). Twenty-four uncooperative children with nNO values < or = 200 ppb performed a second evaluation at least 6 months later and mean levels increased from 104.7+/-10.5 ppb to 169.9+/-19.6 ppb (p<0.05). In the 15 collaborative children nNO levels were higher during the breath holding manoeuvre (687.7+/-96.9 ppb) than during the tidal breathing manoeuvre (335.9+/-57.9 ppb; p<0.05). CONCLUSIONS: Healthy children have higher nNO levels than PCD patients. In 15% of uncooperative healthy children can be found low nNO levels, similar to PCD patients, but those values increased some months later, in successive evaluations. Nasal NO may be used for PCD screening even though repeated evaluations may be necessary in young children.

Exhaled nitric oxide daily evaluation is effective in monitoring exposure to relevant allergens in asthmatic children.

BACKGROUND: Though asthma is an airway inflammatory disease, the assessment of treatment efficacy is mainly based on symptom monitoring and the evaluation of lung function parameters. This study was aimed to evaluate the feasibility of exhaled nitric oxide monitoring in allergic asthmatic children who were exposed to relevant allergens in their homes. METHODS: Twenty-two children allergic to mites underwent twice-daily fractional exhaled nitric oxide (FeNO) therapy using a portable device (NIOX MINO; Aerocrine AB; Stockholm, Sweden) and peak expiratory flow (PEF) measurements before, during, and after periods of natural exposure to mite allergens. The children were admitted to the study if they had lived in a mite-free environment for 3 months. They were observed in this environment for 10 days and then were moved to a site with natural mite exposure at sea level for 19 days. Finally, they were relocated to the mite-free environment for a period of 6 days for follow-up measurements. RESULTS: Significant differences were seen between the mite-free baseline FeNO level (26.4 parts per billion [ppb]; range, 19.3 to 36.2 ppb) and FeNO levels measured during natural mite exposure (37.3 ppb; 27.3 to 51 ppb) and after natural mite exposure (34.9 natural mite exposure; 25.2 to 48.2 ppb). Six children reported asthma symptoms during the mite exposure, and an increase in FeNO was observed in each case (p<0.031); PEF values showed no significant differences, whether between the different environments or between different periods. CONCLUSIONS: These data give further evidence for a possible role of frequent determinations of FeNO in order to promptly assess changes in the level of airway inflammation in asthmatic children.