Feasibility of structured light plethysmography for the evaluation of lung function in preschool children with asthma.

BACKGROUND: Structured light plethysmography (SLP) is a new noninvasive technology to capture the movement of the thoracic and abdominal wall, and to assess some parameters indicative for lung function. OBJECTIVE: The purpose of the study was to evaluate the feasibility of SLP in children with asthma. METHODS: A total of 52 patients were enrolled: 25 with asthma exacerbation (group 1), 13 with well-controlled asthma (group 2), and 14 healthy controls (group 3). Every patient underwent SLP evaluation and a lung function test. RESULTS: SLP evaluations showed that the ratio of inspiratory flow at 50% of tidal volume (Vt) to expiratory flow at 50% of Vt, in which Vt is taken to be the exhaled chest wall movement, and flow is taken to be the time derivative of the chest wall movement (IE50) value increased in group 1 compared with groups 2 and 3, with statistical significance (p = 0.018); the data were consistent with the spirometry parameter. A correlation between the IE50 and forced expiratory volume in the first second of expiration was highlighted (r = -0.35, p = 0.019). CONCLUSION: SLP assessed airway obstruction, and its use in clinical practice could be applied in preschool children in future studies.

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.

Microorganism-induced exacerbations in atopic dermatitis: a possible preventive role for vitamin D?

Atopic dermatitis (AD) is a common skin disease characterized by a complex pathogenesis not completely understood despite numerous studies to date. The clinical patterns result from interactions between genetic disorders determining abnormalities in the epidermis differentiation complex, modification of the cutaneous barrier, and dysfunction of immune responses. Several studies have shown that an alteration of the skin barrier combined with immune dysfunction is important for the onset, maintenance, and risk of exacerbations of the disease. In recent years, new aspects regarding the pathogenesis of the disease, such as the effects of vitamin D (VD) on immunity at the skin level and the role of certain microorganisms (particularly Staphylococcus and Malassezia species) on eczema exacerbations, have been evaluated. This article provides an overview of the evidences supporting the link between VD (deficiency) and microorganisms (skin colonization/sensitization) in AD pathogenesis, based on comprehensive review of the literature. By considering different aspects of disease, it might be possible to improve our understanding, particularly in those patients refractory to conventional treatments. An electronic research strategy was used to search in Medline Pub-Med Library using as research words AD, exacerbation, VD, Staphylococcus aureus (SA), and Malassezia. The results were downloaded and analyzed for systematic review. Few studies actually consider the relationship between VD deficiency (VDD), AD, and SA and Malassezia, but many suggest a correlation between these factors. VDs play a major role against microorganisms in the development of AD and should be considered when treating patients.

Correlation of skin barrier impairment in atopic dermatitis with aeroallergen sensitization.

BACKGROUND: Atopic dermatitis (AD) often predates the development of allergic sensitization in the so-called atopic march. Several studies have pointed out epidermal barrier impairment as a major cause of this evolution. OBJECTIVE: The present study aimed to assess atopic skin integrity by means of transepidermal water loss (TEWL) and Corneometer, and to investigate possible correlations between barrier integrity measurements and the degree of sensitization to aeroallergens (allergy score). METHODS: Sixty-one children (6 months to 17 years old) with AD were clinically evaluated by the Scoring Atopic Dermatitis index. TEWL and Corneometer evaluations were performed on lesion sites as well as on healthy skin. The subjects underwent skin-prick testing, and the severity of allergic sensitization was assessed for each patient by summing all wheal diameters (the allergy score). The same tests were performed in 20 children without AD. RESULTS: In patients with AD, TEWL and Corneometer results were found to be higher and lower, respectively, on eczematous areas in comparison with healthy skin, and differences were significantly correlated to the Scoring Atopic Dermatitis index (p < 0.0001 and p = 0.007, respectively). The TEWL result was significantly higher in nonlesional skin of the patients with AD compared with that of individuals without AD (p = 0.017). Of the patients with AD, 59% were sensitized to inhalant allergens; allergy scores were positively correlated with both AD duration (r = 0.63; p < 0.0001) and nonlesional skin TEWL values (r = 0.46; p = 0.002). No significant correlation was found between allergy scores and skin parameters in subjects without AD. CONCLUSION: Patients with AD are affected by barrier function impairment, even on noneczematous skin. This defect is associated with greater aeroallergen sensitization and may contribute to allergic respiratory symptom development.

Analysis of urinary parameters as risk factors for nephrolithiasis in children with celiac disease.

PURPOSE: Intestinal malabsorption can cause urinary stone disease via enteric hyperoxaluria. It has been shown that celiac disease, a common malabsorption disorder, is associated with an increased risk of calcium oxalate kidney stones in adults. Since no published data are available in the pediatric population, we analyzed urinary excretion of electrolytes in children with celiac disease to assess the risk of nephrolithiasis. MATERIALS AND METHODS: The study population consisted of 115 children 1 to 16 years old (mean 5 years) with positive serological tests for celiac disease (anti-endomysium and anti-tissue transglutaminase antibodies) referred to us for jejunal biopsy to confirm the diagnosis. Assessment was requested because patients presented with poor growth, anemia, gastrointestinal disorders or a family history of celiac disease. After obtaining informed consent we performed urine tests to measure urinary variables and blood tests to exclude metabolic disorders and evaluate renal function. RESULTS: All patients had a biopsy confirmed diagnosis of celiac disease. Oxaluria was normal in all children studied. However, levels of urinary calcium were decreased in patients with celiac disease and were inversely associated with disease severity (p = 0.0004). CONCLUSIONS: In contrast to adults, increased urinary excretion of oxalate was not detectable in children presenting with celiac disease. Therefore, the risk of nephrolithiasis appears not to be increased compared to healthy children. The observed hypocalciuria probably further decreases the tendency to form kidney stones.

Immune regulatory cytokines in the milk of lactating women from farming and urban environments.

Children living on farms have fewer allergies. It is unclear whether breastfeeding in different environments contributes to preventing allergies by exposing offspring to different cytokines that can modulate immune responses. The aim of this study was to quantify and compare levels of Transforming Growth Factor-beta1 (TGF-beta1) and Interleukin-10 (IL-10) in the colostrum and mature milk of mothers living in towns at sea level (references) and mothers on farms. Milk samples were collected within 3 days postpartum (colostrum) and at the first month of the baby's life (mature milk). Sixty-nine reference mothers and 45 farm mothers participated in the study. TGF-beta1 concentrations were significantly higher both in the colostrum (p < 0.05) and in mature milk (p < 0.05) of farm mothers. In the reference mothers, a significant decrease in TGF-beta1 concentrations was observed between colostrum (650, range 0-8000 pg/ml) and mature milk (250, range 0-8000 pg/ml) (p < 0.05). In farm mothers, TGF-beta1 concentrations were 1102 pg/ml (range 0-14,500) in colostrum and remained high in mature milk (821 pg/ml, range 0-14,650). IL-10 concentrations were higher in the mature milk of farm mothers (p < 0.05). No significant differences in IL-10 were observed between colostrum and mature milk in the control group (15 pg/ml, range 0-1800, and 0 pg/ml, range 0-230) or in farm mothers (9.5 pg/ml, range 0-1775, and 14.2 pg/ml, range 0-930), respectively. Exposure to a farm environment is associated with higher concentrations of TGF-beta1 and IL-10 in breast milk when compared to exposure to an urban environment. Higher cytokine concentrations in breast milk may influence early modulation of the development of an immune response, leading to a reduced prevalence of allergy-related diseases in farm children.

Children with nocturnal asthma wheeze intermittently during sleep.

Nocturnal asthma indicates poor overall control of asthma and adversely affects the quality of life of the patient. The purpose of the present study was to compare the objective measurement of nocturnal wheeze with clinical state, recall of symptoms, and changes in lung function. Nine asthmatic children aged 9 to 16 years were followed with an asthma diary and diurnal measurement of peak flow for a week before the nocturnal study; all but two were apparently well controlled. Breath sounds were recorded and analyzed continuously overnight to quantify wheeze using a phonopneumography sensor attached over the trachea. The analytical system (PulmoTrack) utilized an algorithm to detect wheeze and reject interference. The wheeze rate (Tw/Ttot = duration of wheeze/duration of recording) was calculated minute by minute throughout the night. Recordings lasted over 8 hours and all but two children had wheeze lasting for a total time of between 11 and 87 minutes. The pattern of wheezing was very variable during sleep, with episodes of wheeze separated by periods of quiet breathing. There was no relationship between subjective perception of nocturnal asthma, forced expiratory volume in 1 s (FEV(1)) next morning, and the objective measurement of wheeze. Total overnight wheeze was significantly related to the total diary symptom score and to the (small) diurnal variability of peak expiratory flow (PEF). Four of the seven children with asthma who were apparently well controlled had considerable amounts of wheeze during the night that was episodic in nature and unrelated to conventional measures of lung function or nocturnal symptoms.

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.

Effective desensitization to imiglucerase in a patient with type I Gaucher disease.

We describe a child who had anaphylactic hypersensitivity to imiglucerase therapy for Gaucher disease. Treatment was stopped and symptoms returned. After immune desensitization to imiglucerase using a rush protocol, the patient was able to resume treatment and has not had further hypersensitivity complications to date.

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.

Exhaled air temperature in asthmatic children: a mathematical evaluation.

Recently, the exhaled breath temperature has been proposed as a potential marker for the evaluation of airway inflammation in asthma. The purpose of this study was to verify the ability to distinguish asthmatics from normal controls by a dedicated detailed mathematical evaluation of the exhaled air curve. Analysis was performed in the different phases of the curve of exhaled temperature, i.e. the rate of temperature increase (Delta e degrees T) and the mean plateau value. Principal components analysis (PCA) and artificial neural networks (ANNs) were used for the evaluation of the data in 90 asthmatic children and in 33 healthy age-matched controls. Both PCA and ANNs showed that a separation between patients and controls can be obtained only by the evaluation of the plateau phase of the curve, which better reflects the periphery of the airway.

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.

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.

Formoterol, montelukast, and budesonide in asthmatic children: effect on lung function and exhaled nitric oxide.

BACKGROUND: It has been proposed that asthma control may be achieved in part by minimizing airway inflammation. The simultaneous effects of inhaled steroids associated with long-acting beta-agonists and leukotriene antagonists on pulmonary function and airway inflammation are still largely unexplored in children with moderate persistent asthma. OBJECTIVES: The aim of this study was to investigate the effects of add-on therapy with long-acting beta-agonists and leukotriene antagonists on FEV1 and exhaled nitric oxide levels (FENO) in children. METHODS: Forty-eight steroid-naïve atopic asthmatic children, 7-11 years of age, were randomly treated in four groups for two consecutive one-month periods, as follows: (1) first month: budesonide 200 microg twice daily; second month: budesonide 400 microg twice daily; (2) first month: budesonide 200 microg twice daily+formoterol 9 microg twice daily; second month: budesonide 200 microg twice daily+montelukast 5mg once daily; (3) first month: budesonide 200 microg twice daily+montelukast 5mg once daily; second month budesonide 200 microg+formoterol 9 microg twice daily; (4) first and second month: budesonide 400 microg twice daily. RESULTS: All treatments resulted in a significant increase in lung function and a decrease in FENO compared with values at baseline. Budesonide+montelukast in combination was the most effective treatment for reducing FENO levels. CONCLUSION: This study demonstrates that add-on therapy with montelukast plus low-dose budesonide is more effective than the addition of long-acting beta-agonists or doubling the dose of budesonide for controlling FENO in asthmatic children.

Biomarkers of neutrophilic inflammation in exhaled air of cystic fibrosis children with bacterial airway infections.

Leukotriene B(4) (LTB(4)) and interleukin-8 (IL-8) are inflammatory mediators involved in the neutrophil response to pulmonary bacterial colonization in cystic fibrosis (CF). The aim of this study was to investigate whether the LTB(4) and IL-8 levels in exhaled breath condensate (EBC) could be related to the type of bacterial colonization in CF patients. The pH level in EBC was analyzed as an estimate of airway acidification. Forty children were evaluated: 10 CF patients with P. aeruginosa, 10 CF patients with S. aureus, 10 not colonized CF patients, and 10 healthy children. LTB(4) and IL-8 in EBC were analyzed by specific enzyme immunoassay kits (EIA). The pH of EBC was measured with a pH-meter after deareation by bubbling with argon. Exhaled LTB(4) was higher in CF children with P. aeruginosa compared to those with S. aureus (P < 0.01), not colonized (P < 0.001), and healthy children (P < 0.01). Exhaled IL-8 was elevated in CF patients colonized by P. aeruginosa compared with other subgroups (vs. not colonized, P < 0.05; vs. healthy children, P < 0.001). IL-8 levels were higher in CF children with S. aureus than in healthy children (P < 0.05). There was an increase in IL-8 levels in not colonized CF patients compared with healthy children (P < 0.05). EBC pH was higher in healthy children compared to CF patients not colonized (P < 0.05). Our data suggest that EBC is suitable for evaluating neutrophil inflammatory mediators (LTB(4), IL-8, and pH) involved in the response to pulmonary bacterial colonization in CF children.

Asthma and viruses: is there a relationship?

Asthma is a multifactorial disease in which many factors play a role in its development and exacerbations. Viral infections are known to be the main cause of asthmatic exacerbations and are often the first manifestation of asthma in preschool age. However, there is much evidence suggesting a role of viral infections even in asthma development. Respiratory Syncytial Virus (RSV). has been first associated with an increased risk to develop asthma, but recently new viruses have been proposed to be involved in asthma pathogenesis. Further studies will be needed to demonstrate a causative role of viral infections in asthma development, in order to implement preventive strategies in high-risk children.