Early decrease in nasal eosinophil proportion after nasal allergen challenge correlates with baseline bronchial reactivity to methacholine in children sensitized to house dust mites.

BACKGROUND: Allergic rhinitis is induced by an IgE mediated inflammation after allergen exposure of the membranes lining the nose which, in predisposed individuals, may constitute a risk factor for the occurrence of asthma. OBJECTIVE: To detect early changes in nasal inflammation after allergen exposure, 11 children [9.0 (7, 11) yrs], sensitized to house dust mites (HDM), with rhinoconjunctivitis and asthma and an age- and gender-matched control group (Ctr) were studied. METHODS: The following parameters were evaluated: i) pulmonary function; ii) bronchial reactivity to methacholine (MCh), expressed as Pd20MCh; iii) nasal brushing (NB) 'at baseline' and, on a separate day, 30 min after nasal allergen challenge (NAC). On NBs, the following markers of inflammation were evaluated: a) neutrophil and eosinophil proportion, b) 'intact to degranulated eosinophil' ratio, and c) expression of intercellular adhesion molecule (ICAM)-1 and HLA-DR by nasal epithelial cells. RESULTS: 'At baseline', allergic children showed elevated nasal eosinophilia and increased ICAM-1 and HLA-DR expression (p<0.05), as compared to Ctr. In allergic children, nasal eosinophilia correlated with Pd20MCh (p=0.002). The significant decrease in nasal eosinophilia observed after NAC (p=0.002) was associated with a significant decrease in the 'intact to degranulated eosinophil' ratio (p=0.001). Interestingly, correlations were still present between Pd20MCh and 'post NAC' eosinophilia (p=0.004) or the NAC-induced decrease in eosinophilia (p=0.010). CONCLUSIONS: In children sensitized to HDM, experimental allergen exposure is followed by an early depletion of nasal eosinophils. The correlation between allergen-induced changes in nasal eosinophilia and bronchial reactivity to MCh further supports the concept of a tight link between upper and lower respiratory tract involvement in respiratory allergy.

Long-lasting myopathy as a major clinical feature of sarcoidosis in a child: case report with a 7-year follow-up.

Muscle involvement in sarcoidosis is rarely described as the predominant feature and muscular symptoms are seldom observed. In recent pediatric series, sarcoid myopathy was no longer considered a typical aspect of sarcoidosis. The authors report a case of sarcoidosis in a patient presenting predominant muscular symptoms since childhood, due to biopsy-proven muscle localization. A seven-year follow-up has demonstrated a slow improvement of symptoms with persistency of electromyography (EMG) and biochemical abnormalities. Mild and transient pulmonary involvement was demonstrated only after diagnosis. Clinical improvement associated with a decrease in serum muscular enzyme levels with no changes in EMG was observed after a six-month course of systemic corticosteroid therapy. In childhood, skeletal muscle symptoms may be the presenting feature of sarcoidosis.

e-NO peak versus e-NO plateau values in evaluating e-NO production in steroid-naive and in steroid-treated asthmatic children and in detecting response to inhaled steroid treatment.

SUMMARY. Airway nitric oxide (NO) production can be measured by chemiluminescence analyzer in children able to perform a single low exhalation. The aim of the present study was to evaluate whether exhaled NO (e-NO) peaks (first part of the exhalation) were as useful as e-NO plateaus (last part of the exhalation) in evaluating e-NO production in asthmatic children and in detecting responses to inhaled steroid treatment. E-NO peak, plateau, and rate of production values were measured in 100 atopic asthmatic children using a chemiluminescence analyser. Thirty-seven patients (mean age, 11.1 +/- 0.7 years) were receiving inhaled steroids (flunisolide, 0.8-1 mg daily) or beclomethasone (0.2-0.4 mg daily), while the remaining 63 (mean age, 12.0 +/- 0.4 yrs) were-steroid naive and treated only with inhaled beta(2)-agonists on an as-needed basis. Fifteen out of the 63 steroid-naive patients were reevaluated after a short course (3 weeks) of inhaled corticosteroid treatment (flunisolide, 0.8-1 mg daily, or beclomethasone, 0.2-0.4 mg daily). Regardless of the type of data analysis (peak, plateau, or rate of production), the e-NO values of the steroid-naive patients were significantly higher than those of inhaled steroid-treated patients (P < 0.01, each comparison). Similarly, in the subgroup of steroid-naive patients, the three methods were able to detect a decrease in e-NO levels by inhaled steroid therapy (P < 0.001, each comparison). Plotting the difference between e-NO peak and e-NO plateau values against their average, the peak e-NO concentrations were higher than e-NO plateau values. This difference was independent of the absolute e-NO concentration. The results of the two types of data analysis seems to agree more closely in steroid-naive patients than in steroid treated patients, or in the subgroup of steroid-naive patients who received a short course treatment with inhaled steroids. In steroid-treated subjects, the differences were up to five times higher for peak than plateau e-NO values. These data suggest that both e-NO plateau and e-NO peak values are useful in detecting airway NO production in atopic asthmatic children, but they cannot be used interchangeably. Because of possible nasal contamination in e-NO peak measurement, we prefer e-NO plateau levels for evaluating lower airway e-NO production.

How can we best read exhaled nitric oxide flow curves in asthmatic children?

Orally exhaled nitric oxide (NO) levels are increased in children with asthma and thought to reflect the local inflammatory events in the airways. NO production in the lower respiratory airway is reflected in the plateau values of the NO curve, recorded while the patient is performing a slow vital capacity manoeuvre. In young patients, however, plateau values may be difficult to obtain, because the slow vital capacity manoeuvre is often terminated prematurely. In the present study, 60 steroid-naive atopic asthmatic children and 17 normal age-matched controls were asked to perform a slow vital capacity manoeuvre, during which fractional exhaled NO (FEno) levels were measured and evaluated as: a) FEno plateau levels of last part of exhalation (NO plateau); b) FEno peak values, c) area under the FEno curve (AUC). Thirteen out of the 60 steroidnaive patients were reevaluated after a short course of inhaled corticosteroid treatment. Independently of the type of data analysis, FEno values of asthmatics were significantly higher than those observed in normal controls (P < 0.001, each comparison). In addition, possibly because of upper airway NO contamination, FEno peak values were significantly higher than FEno plateau levels in asthmatic patients and in control subjects (P < 0.001, each comparison). Both in asthmatics and controls, highly positive correlations were observed between: a) FEno plateau and peak values (r > 0.7, P < 0.01, each correlation), b) FEno plateau and AUC values (r > 0.7, P < 0.01, each correlation) and c) FEno peak and AUC values (r > 0.9, P < 0.001, each correlation). In asthmatic patients, the three types of data analysis were equally sensitive in detecting the decrease in FEno levels induced by inhaled steroid therapy (P < 0.05, each comparison), with a good correlation between the three data analyses (r > 0.5, P < 0.05, each correlation). Thus, although quantitatively different, comparable data reflecting airway inflammation can be obtained evaluating FEno plateau, FEno peak, and area under the curve, on account of possible upper airway contamination in FEno peak, FEno plateau should be preferred to measure lower airway NO production.

Clinical application of bronchoscopy and bronchoalveolar lavage in the immunocompromised host.

Pulmonary complications are the most frequent cause of morbidity and mortality in immunocompromised patients. The speed of clinical assessment and the initiation of appropriate therapy is critically related to survival. Fibreoptic bronchoscopy and bronchoalveolar lavage (BAL) had proved useful in making the diagnosis of pulmonary complications in a high proportion of immunocompromised patients, where less invasive techniques, such as blood cultures or sputum induction, have failed to establish a diagnosis. Bronchoscopy and BAL cause little discomfort and low morbidity, and should be performed as early in the disease course as possible, preferably before the onset of respiratory failure.

[Gastroesophageal reflux disease and respiratory disease]. / Malattia da reflusso gastro-esofageo e patologia respiratoria.

The patients treated for oesophageal atresia present a correlation between the clinical sintomatology after recanalization characterized by disfagia, dispnea, recurrent cough, chronic pneumopaties and oesophageal anomalies. Where morphological alterations accounting for the presence of gastro-oesophageal reflux (GOR) were not evident, possible functional alterations of the motility were considered. The incidence of GOR was considerably high and, expression of a congenital alteration of the lower oesophageal sphincter and of oesophageal peristalsis, becomes even more severe due to further stretching of the gastro-esophageal junction. The authors underline that the early demonstration of histological changes, even before recanalization, and the motility disorders of the oesophagus have to be well studied, while the LES is normalized, in order to prevent and treat the possible appearance of the well-known complications of GOR.

[Holotelencephaly: description of a case]. / Olotelencefalia: descrizione di un caso.

This study describe a case of SNC malformation that belongs to the prosencephalization defects. Particularly, the degree of cerebral anomalies and the gravity of facial abnormalities place the case in the group of Holotelencephalies. We have considered the ethiopathogenetic connections that can cause such embryonic damage, the clinical characteristics, the evolution and the prognosis, by the light of the dates provided by literature. Our patient is a six month-old female put under observation since her birth.

IgE in childhood asthma: relevance of demographic characteristics and polysensitisation.

BACKGROUND: Despite the therapeutic efficacy of the anti-IgE monoclonal antibody, the role of IgE in allergic asthma is still a matter of debate. This may be mostly relevant in childhood, where a wide range of total serum (s) IgE levels is often detected. AIM: To evaluate whether the relationships between total or allergen-specific sIgE levels and the clinical markers of allergic inflammation and the pulmonary function values might be affected by the demographic characteristics of the patients or by the presence of multiple sensitisations to allergens. METHODS: 64 asthmatic children sensitised to house dust mites (HDM) were evaluated. The role of age, sex and multiple sensitisations was evaluated by multiple regression model (MRM) analysis. RESULTS: Total and HDM-specific sIgE levels (Log) showed similar moderate-to-strong correlations with exhaled nitric oxide (FENO) and blood eosinophilia (Log) (p<0.0001) but not with forced vital capacity, forced expiratory volume in 1 s (FEV(1)), %FEV(1) change after salbutamol. The positive associations between total sIgE levels and Log FENO levels or Log blood eosinophilia were also detected by MRM analysis. Age brought a negative, although limited, contribution to FENO levels and blood eosinophilia (p<0.043). Positive similar associations were also detected between HDM-specific sIgE levels and FENO levels or blood eosinophilia; however, no significant contribution of age or of other covariates was detected. CONCLUSION: In childhood allergic asthma, total and HDM-specific sIgE levels are tightly linked to markers of allergic inflammation but not to pulmonary functions. These relationships are weakly affected by age but not by sex or by the presence of multiple sensitisations.

Discharge report accuracy.

The clinical report is one of the most useful ways of cooperation between the hospital doctors and general practitioners. This paper is aimed at checking the accuracy of clinical reports in an Italian children's hospital. The authors examined 200 clinical reports after establishing some criteria to be fulfilled in order to write a good clinical report. Only 18 reports were considered good; the results were discussed with the physicians who had written the reports. At a second evaluation, the authors checked the efficacy of the proposed changes: 97 clinical reports were considered good.

Dissociation between exhaled nitric oxide and hyperresponsiveness in children with mild intermittent asthma.

BACKGROUND: Bronchial hyperresponsiveness and airway inflammation are distinctive features of asthma. Evaluation of nitric oxide (NO) levels in expired air have been proposed as a reliable method for assessing the airway inflammatory events in asthmatic subjects. A study was undertaken to evaluate whether airway hyperresponsiveness is related to levels of exhaled NO. METHODS: Thirty two steroid-naive atopic children with mild intermittent asthma of mean (SD) age 11.8 (2.3) years and 28 age matched healthy controls were studied to investigate whether baseline lung function or airway hyperresponsiveness is related to levels of exhaled NO. Airway responsiveness was assessed as the dose of methacholine causing a 20% decrease in forced expiratory volume in one second (FEV(1)) from control (PD(20) methacholine) and exhaled NO levels were measured by chemiluminescence analysis of exhaled air. RESULTS: At baseline asthmatic children had significantly higher NO levels than controls (mean difference 25.87 ppb (95% CI 18.91 to 32.83); p<0.0001) but there were no significant differences in lung function parameters (forced vital capacity (FVC), FEV(1) (% pred), and forced expiratory flows at 25-75% of vital capacity (FEF(25-75%))). In the asthmatic group exhaled NO levels were not significantly correlated with baseline lung function values or PD(20) methacholine. CONCLUSIONS: These results suggest that levels of exhaled NO are not accurate predictors of the degree of airway responsiveness to inhaled methacholine in children with mild intermittent asthma.

Orally exhaled nitric oxide levels are related to the degree of blood eosinophilia in atopic children with mild-intermittent asthma.

Increased levels of nitric oxide have been found in expired air of patients with asthma, and these are thought to be related to the airway inflammatory events that characterize this disorder. Since, in adults, bronchial inflammatory changes are present even in mild disease, the present study was designed to evaluate whether a significant proportion of children with mild-intermittent asthma could have increased exhaled air NO concentrations. Twenty-two atopic children (aged 11.1+/-0.8 yrs) with mild-intermittent asthma, treated only with inhaled beta2-adrenoreceptor agonists on demand and 22 age-matched controls were studied. NO concentrations in orally exhaled air, measured by chemiluminescence, were significantly higher in asthmatics, as compared to controls (19.4+/-3.3 parts per billion (ppb) and 4.0+/-0.5 ppb, respectively; p<0.01). Interestingly, 14 out of 22 asthmatic children had NO levels >8.8 ppb (i.e. >2 standard deviations of the mean in controls). In asthmatic patients, but not in control subjects, statistically significant correlations were found between exhaled NO levels and absolute number or percentage of blood eosinophils (r=0.63 and 0.56, respectively; p<0.01, each comparison). In contrast, exhaled NO levels were not correlated with forced expiratory volume in one second (FEV1) or forced expiratory flows at 25-75% of vital capacity (FEF25-75%) or forced vital capacity (FVC), either in control subjects, or in asthmatic patients (p>0.1, each correlation). These results suggest that a significant proportion of children with mild-intermittent asthma may have airway inflammation, as shown by the presence of elevated levels of nitric oxide in the exhaled air. The clinical relevance of this observation remains to be established.

Dextrothyroxine treatment of phosphorylase-kinase deficiency glycogenosis in four boys.

Four boys, aged 2 years 5 months to 3 years 7 months, with large hepatomegaly due to phosphorylase-kinase deficiency glycogenosis, were given a trial of sodium dextrothyroxine (D-T4) at a mean dose of 0.165 mg/kg/day for an average period of 6 months. Phosphorylase-kinase was undetectable in the haemolysates of erythrocytes (3 patients) or in the liver (one patient) before, and still undetectable in the haemolysates of the four patients during treatment, thus pointing to X-linked phosphorylase-kinase deficiency glycogen storage disease (GSD IXb). D-T4 administration resulted in complete normalization of liver size, decrease of serum GOT (p less than 0.02), GPT (p less than 0.05) and triglycerides (p less than 0.01) to normal values, as well as correction of mild asymptomatic hypoglycemia (p less than 0.01). As long as the outcome of type IXb glycogenosis in adult life remains undefined, dextrothyroxine therapy seems an effective means of reducing liver size and correcting part of the biochemical abnormalities of the disease.

Time-dependent changes in orally exhaled nitric oxide and pulmonary functions induced by inhaled corticosteroids in childhood asthma.

Exhaled nitric oxide levels are elevated in asthmatic children and decrease after inhaled steroid treatment. We evaluated the time-dependent changes in fractional exhaled nitric oxide concentration (FENO) and pulmonary function parameters following inhaled steroid therapy. Thirty-nine steroid-naive atopic patients (age 11.92+/-0.48 years) with mild intermittent asthma and 22 age-matched healthy controls were enrolled in the study; pulmonary functions and FE(NO) levels were measured. Low doses of inhaled steroids were prescribed to all asthmatic patients who were reevaluated in a second visit (between 10 and 40 days after the beginning of the treatment). At the enrolment, asthmatic patients had similar forced expiratory volume in 1 sec (FEV1) and forced vital capacity (FVC) values (p > 0.05) but reduced forced expiratory flows at 25-75% of the vital capacity (FEF(25-75%)) values, as compared to controls (p < 0.05). In addition, FE(NO) levels were significantly higher in asthmatics with respect to control subjects (30.8+/-3.0 and 4.0+/-0.5 ppb, respectively; p < 0.01). All asthmatics had FE(NO) levels higher than 8.8 ppb (i.e., > 2 standard deviations of the mean in controls). After steroid treatment, patients showed significant improvement of FEV1, FVC, and FEF(25-75%) (p = 0.0001; each comparison) and a reduction of FE(NO) levels (p = 0.0001). A weak significant correlation was found between percent decrease in FE(NO) levels and percent increase in FEV1 (r = 0.33, p = 0.04) or in FEF(25-75%) (r = 0.4, p = 0.01) after treatment. When changes in FE(NO) levels and in pulmonary function parameters were corrected for days of treatment, significant correlations were still present between percent decrease in FE(NO) levels and percent increase in FEV1 (r = 0.57, p = 0.0004) or percent increase in FEF(25-75%) (r = 0.45, p = 0.006). Sixteen of the 39 asthmatic patients were evaluated on two occasions after the beginning of treatment, at days 10 and 40. The significant reduction in FE(NO) levels (p < 0.01) and the significant increase in FEV1 and FEF(25-75%) values observed (p < 0.05) after 10 days did not further improve at day 40. These data show that it is possible to demonstrate early effects of low-dose inhaled steroids in asthmatic children using objective measurements of airway caliber and inflammation.

Nasal inflammation and bronchial reactivity to methacholine in atopic children with respiratory symptoms.

BACKGROUND: In atopic subjects, dysfunctions of the upper and lower airways frequently coexist and allergic rhinitis seems to constitute a risk factor for the occurrence of asthma in predisposed individuals. AIM OF THE STUDY: To evaluate whether in atopic subjects nasal inflammation could reflect changes in respiratory functions, 11 allergic children, sensitized to house dust mites (HDM), with rhinoconjunctivitis and asthma and 10 nonatopic controls (ctrs) were studied. METHODS: All subjects underwent nasal brushing to detect percentages of nasal eosinophils (Eos %) and intercellular adhesion molecule-1 (ICAM-1) expression by nasal epithelial cells. In the same day pulmonary function tests, i.e. forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), forced expiratory flows at 25-75% of the vital capacity (FEF25-75%) and methacholine (MCh) bronchial inhalation challenge were also evaluated. RESULTS: Pulmonary function parameters were not significantly different in allergic children and in ctrs (P > 0.05), while a significant increase in bronchial reactivity to MCh, expressed as Pd20 MCh, was detected in the former population (P < 0.05). As compared with ctrs, allergic children showed elevated Eos % and ICAM-1 expression (P < 0.05). When nasal inflammation and pulmonary function parameters were compared, a significant correlation was found between nasal Eos % and bronchial reactivity to MCh (P = 0.002). CONCLUSIONS: These data support the concept of significant links between upper and lower respiratory tract involvement in atopic children sensitized to HDM.

Correlations between exhaled nitric oxide levels and pH-metry data in asthmatics with gastro-oesophageal reflux.

BACKGROUND: In gastro-oesophageal reflux (GER), micro-aspirations of gastric fluid may damage the epithelial surface of the airways, an important source of endogenous nitric oxide (NO). OBJECTIVES: The aim of the study was to evaluate the possible influence of GER on fractional exhaled nitric oxide (FE(NO)) release. METHODS: FE(NO) levels were compared in two age-matched groups of allergic children: (1) 20 with mild asthma, responding to standard anti-asthma pharmacologic therapy (asthmatic children) and (2) 12 with mild 'asthma-like symptoms' and GER. RESULTS: No differences in pulmonary functions parameters (FEV(1), FVC and FEF(25-75%)) were found between the two groups of children (p > 0.1); FE(NO) levels were higher in asthmatic children compared with GER children (p = 0.0001). GER children underwent 24-hour oesophageal pH-metry, and possible correlations between pH-metry data, pulmonary functions and FE(NO) levels were evaluated. No correlations were found between pulmonary functions and pH-metry data (p > 0.05, each correlation). In contrast, correlations were observed between FE(NO) levels and pH-metry data, including (1) percentage of study time with pH < 4 (r = -0.80, p = 0.008), (2) number of episodes with pH < 4 (r = -0.76, p = 0.012), and (3) number of episodes >5 min with pH < 4 (r = -0.69, p = 0.02). CONCLUSIONS: Thus, FE(NO) levels are lower in allergic children with 'asthma-like symptoms' and GER as compared to asthmatic children. The correlations between FE(NO) levels and pH-metry data suggest that inhalation of acid gastric content may interfere with NO production in the airways.

Bronchiolitis obliterans organizing pneumonia in three children with acute leukaemias treated with cytosine arabinoside and anthracyclines.

Bronchiolitis obliterans organizing pneumonia (BOOP) is a clinicopathological entity with well-defined diagnostic criteria, which can be idiopathic or produced by a variety of biological processes. We describe the occurrence of BOOP in three children, one with acute lymphoblastic leukaemia and two with acute promyelocytic leukaemia. In the three patients, BOOP developed 10-20 days after a course of therapy with cytosine arabinoside and anthracyclines. The possible relationships between the small conducting airway lesions, lung toxic reaction to the drugs and/or nonidentified infectious agents are discussed.

Exhaled nitric oxide levels in non-allergic and allergic mono- or polysensitised children with asthma.

BACKGROUND: Increased fractional exhaled NO concentrations (FENO) and blood/tissue eosinophilia are frequently reported in allergic children with mild asthma and are thought to reflect the intensity of the inflammation characterising the disease. The aim of this study was to investigate possible differences in FENO levels or in the intensity of the blood eosinophilia in allergic and non-allergic asthmatic children. METHODS: 112 children with stable, mild, intermittent asthma with a positive bronchial challenge to methacholine were consecutively enrolled in the study; 56 were skin prick test and RAST negative (non-sensitised) while 56 were sensitised to house dust mites (23 only to house dust mites (monosensitised) and 33 were sensitised to mites and at least another class of allergens (pollens, pet danders, or moulds)). Nineteen sex and age matched healthy children formed a control group. RESULTS: Compared with non-allergic patients, allergic children had a significantly higher rate of blood eosinophilia (p=0.0001) with no differences between mono- and polysensitised individuals. Forced expiratory volume in 1 second (FEV(1)), forced vital capacity (FVC), forced expiratory flow at 25-75% of vital capacity (FEF(25-75%)), and the degree of bronchial reactivity to methacholine were similar in non-atopic and atopic children, with no differences between mono- and polysensitised individuals. FENO levels measured by chemiluminescence analyser were higher in asthmatic children (15.9 (14.3) ppb) than in the control group (7.6 (1.6) ppb, p=0.04) and higher in allergic patients (23.9 (2.1) ppb) than in non-allergic patients (7.9 (0.8) ppb, p=0.0001), but there were no differences between mono- and polysensitised individuals (p>0.1). Significant correlations between blood eosinophilia and FENO levels were seen only in allergic (r=0.35, p<0.01) and in polysensitised individuals (r=0.45, p<0.05). CONCLUSIONS: In children with mild asthma, a similar degree of functional disease severity may be associated with a higher inflammatory component in allergic than in non-allergic subjects.