Jacopo Pagani

Exhaled nitric oxide in asthmatic and non-asthmatic children: Influence of type of allergen sensitization and exposure to tobacco smoke

Asthmatic bronchial inflammation is associated with increased nitric oxide concentrations in exhaled air (eNO). Recent data suggest that this effect arises from atopy. Our aim in this study was to find out whether atopy and sensitization to particular allergens influences eNO levels. A total of 213 subjects (41 asthmatics and 172 controls) (96 boys and 117 girls, 7.3–14 years of age) were studied. Parents completed a questionnaire that sought information on their childrens respiratory symptoms and exposure to tobacco smoke. Subjects underwent skin‐prick tests for the following common allergens: Dermatophagoides pteronyssinus (Dpt), cat fur, Aspergillus fumigatus, Alternaria tenuis, mixed grass, mixed tree pollen, Parietaria officinalis, egg, and cows milk. eNO was collected in 1‐l mylar bags (exhaled pressure 10 cmH2O, flow 58 ml/s) and analyzed by using chemiluminescence. Atopic and non‐atopic children without a history of chronic respiratory symptoms had a similar geometric mean eNO (atopics, n = 28, 11.2 p.p.b.; non‐atopics, n = 96, 10.0 p.p.b.; mean ratio 1.1, 95% confidence interval [CI]: 0.7–1.6). Conversely, atopic asthmatic subjects had significantly higher eNO values than non‐atopic asthmatic subjects (atopics, n = 25, 24.8 p.p.b.; non‐atopics, n = 16, 11.4 p.p.b.; mean ratio 2.2, 95% CI: 1.2–3.9, p= 0.000). In children with rhinitis alone (n = 15) and those with lower respiratory symptoms other than asthma (n = 33), eNO increased slightly, but not significantly, with atopy. eNO levels correlated significantly with Dpt wheal size (r = 0.51) as well with the wheal size for cat, mixed grass, and Parietaria officinalis (r = 0.30–0.29), and with the sum of all wheals (r = 0.47) (p= 0.000). Subjects sensitized only for Dpt (but not those subjects sensitized only for grass pollen or other allergens) showed significantly higher eNO levels than non‐atopic subjects (16.4 p.p.b. vs. 10.2 p.p.b., mean ratio 1.6, 95% CI: 1.1–2.3, p= 0.002). In asthmatic subjects, Dpt sensitization markedly increased eNO levels (Dpt‐sensitized subjects: 28.0 p.p.b.; Dpt‐unsensitized subjects: 12.2 p.p.b.; mean ratio 2.3, 95% CI: 1.5–3.5, p= 0.000). Non‐asthmatic Dpt‐sensitized subjects also had significantly higher eNO values than non‐asthmatic, non‐Dpt‐sensitized subjects (14.2 p.p.b. vs. 10.1 p.p.b.; mean ratio 1.4, 95% CI: 1.1–1.9, p= 0.008). No difference was found between eNO levels in asthmatic subjects and control subjects exposed or unexposed to tobacco smoke. In conclusion, eNO concentrations are high in atopic asthmatic children and particularly high in atopic asthmatics who are sensitized to house‐dust mite allergen.

Bi-level positive airway pressure (BiPAP) ventilation in an infant with central hypoventilation syndrome

A 4‐month‐old baby girl, after a period of apparent good health, began to have aphonia, dyspnea, difficulties with swallowing, cyanosis, apnea, and hypopnea during sleep that resulted in admission to an intensive care unit for intubation and mechanical ventilation. At the age of 9 months she was admitted to our hospital with a possible diagnosis of central hypoventilation syndrome. A polysomnographic study showed apnea and hypopnea (apnea + hypopnea index = 47.1), hypercapnia (mean end‐tidal P  co 2 89 ± 15.0 mmHg), and arterial desaturation (mean Sa  o 2 91 ± 1.7%; lowest Sa  o 2 < 50%; 68% of total sleep time at Sa  o 2 below 93%); the study also showed an absent ventilatory response to CO2, absent cardiac responses to apnea during sleep, and right ventricular hypertrophy.

Sleep apnoea in children with diabetes mellitus: effect of glycaemic control

Aims/hypothesis. Patients with diabetes mellitus commonly have cardiovascular autonomic dysfunction and an abnormal ventilatory pattern during sleep. Few data are available on these changes in childhood diabetes. We investigated whether young diabetic children with or without diabetic neuropathy have ventilatory dysfunction during sleep and if so, whether these autonomic changes are related to the duration of diabetes and glycaemic control.¶Methods. We studied 25 children with insulin-dependent diabetes mellitus (19 boys, mean age 7.72 ± 1.99 years). All patients were insulin-dependent at diagnosis; blood samples for HbA1 c assay were collected on the morning before testing and at 3-month intervals during the preceding year. Patients and control subjects (20 age-matched healthy children, 15 boys) underwent overnight polysomnography.¶Results. More diabetic patients than control subjects had sleep apnoeas (p = 0.006); apnoeas in patients also lasted longer (p = 0.07). Patients with poorly controlled diabetes had more apnoeas than patients with well–controlled diabetes and than healthy control subjects (p < 0.0001). Respiratory events during sleep correlated significantly with glycaemic control (r = 0.360; p = 0.09) and with the duration of diabetes (r = 0.430; p = 0.04).¶Conclusion/interpretation. We conclude that respiratory control is compromised very early in children with diabetes. These anomalies are closely related to the duration of diabetes and to glycaemic control. In young children with diabetes, screening of ventilatory control using recording techniques that are simpler than polysomnography could provide an early indication that an adverse cardiopulmonary reaction has begun. [Diabetologia (2000) 43: 696–702]

NREM sleep instability changes following rapid maxillary expansion in children with obstructive apnea sleep syndrome

OBJECTIVE To evaluate NREM sleep microstructure in children with obstructive sleep apnea syndrome (OSAS) before and after one year of rapid maxillary expander (RME) treatment by means of the cyclic alternating pattern (CAP). METHODS Nine children with OSAS aged 4-8 years (6 males, mean age 6.4+/-1.97 years) and age-matched normal controls were included. All subjects underwent an overnight polysomnography in the sleep laboratory after one adaptation night, as a baseline evaluation; children with OSAS were recorded again after one year of RME treatment. RESULTS After one year of treatment the OSAS group showed a longer duration of time in bed and sleep period time, a reduction in number of stage shifts compared to baseline recordings, and the apnea-hypopnea index decreased significantly. At baseline, the OSAS group had a higher CAP rate during slow-wave sleep and an increased A2 index compared to normal controls. After one year of RME application, children with OSAS showed an increase in CAP rate associated with an increase of A1 index during slow-wave sleep. CONCLUSIONS RME treatment almost normalized sleep architecture and improved sleep respiratory disturbances; however, sleep microstructure and respiratory parameters did not completely recover. The persistence of increased CAP rate in slow-wave sleep associated with an increase of A1 index might reflect a partial failure of orthodontic treatment. On the other hand, the rebound of A1 subtypes might be an indirect sign of an attempt to normalize sleep that has been disturbed by the respiratory events.

Association of asthma with extra-respiratory symptoms in schoolchildren: Two cross-sectional studies 6 years apart

Epidemiological information on symptoms affecting extra‐respiratory organs and apparatuses in asthmatic children is scarce. The aim of this study therefore was to evaluate, at a population level, if and what extra‐respiratory symptoms are associated with asthma. Two questionnaire‐based, cross‐sectional surveys were carried out on 1,262 students (651 males; mean age 9.57 years, age‐range 6–14 years) in 1992 and on 1,210 students (639 males; mean age 9.02 years, age‐range 6–14 years) in 1998, from two elementary and two junior high schools in Rome, Italy. Questionnaires included queries about asthma and its risk factors and extra‐respiratory symptoms (headache, restlessness, sleep disturbances, urticaria, itching, and abdominal pain). Of responders, 11.9% (279/2,342) had a history of asthma. After adjustment for gender, family history of atopic disease, low birth weight, early respiratory problems, and damp house, asthma was significantly associated with recurrent abdominal pain (odds ratio [OR] 1.90; 95% confidence interval [CI]: 1.04, 3.16), itching (OR 3.15; 95% CI: 1.75, 5.68), and urticaria (OR 2.52; 95% CI: 1.02, 6.20). Asthma was reported by 10.2% (201/1,962) of children unaffected by this triad, by 20.1% (56/279; OR 2.20) with one of the symptoms, and by 31.6% (12/38; OR 4.04) with two or more symptoms. An emerging characteristic of pediatric asthma in our setting appears to be its association with certain extra‐respiratory symptoms (abdominal pain, itching, and urticaria). A global, internistic approach to asthmatic children is increasingly required both in the clinical setting and in future epidemiological studies.

Diffusing capacity for carbon monoxide in children with type 1 diabetes

Aims/hypothesisFew data are available on lung dysfunction in children with diabetes. We studied the association of pulmonary function variables (flows, volumes and alveolar capillary diffusion) with disease-related variables in children with type 1 diabetes mellitus.MethodsWe studied 39 children with type 1 diabetes (mean age 10.9±2.6 years, disease duration 3.6±2.4 years, insulin·kg−1·day−1 0.77±0.31) and 30 healthy control children (mean age 10.4±3.0 years). Pulmonary function tests included spirometry, N2 wash-out and the single-breath diffusing capacity for carbon monoxide (DLCO) corrected for the alveolar volume (DLCO/VA). Glycaemic control was assessed on the basis of HbA1c, with HbA1c values of 8% or less considered to indicate good glycaemic control, and HbA1c values of 8% or more considered to indicate poor control.ResultsChildren with poor glycaemic control had comparable percentage values for predicted flows and volumes but lower DLCO/VA values than children with good glycaemic control and healthy control children (86.7±12.6 vs 99.8±18.4 and 102.0±15.7; p<0.05). The predicted DLCO/VA percentages correlated with HbA1c levels (r=−0.39, p=0.013). A multiple regression analysis (stepwise model) controlling for HbA1c levels and other disease-related variables (age of disease onset, disease duration, daily insulin dose/kg, sex) identified HbA1c levels as the sole predictor of DLCO/VA in percent.Conclusions/interpretationIn children with type 1 diabetes, the diffusing capacity diminishes early in childhood and is associated with poor metabolic control. Although low DLCO/VA levels in these children probably reflect pulmonary microangiopathy induced by type 1 diabetes, other factors presumably influencing CO diffusion capacity measurements (e.g. a left shift in HbA1c resulting in high O2 binding and low CO binding) could explain the apparent capillary and alveolar basal membrane dysfunction.

Immediate skin reactivity to histamine and to allergens in cohorts of 9-year-old schoolchildren studied 16 years apart.

Background Differing or increasing prevalence of positive allergen skin‐prick tests observed in Europe could at least in part be explained by population changes in histamine skin reactivity. These changes would also alter the relationship between positive allergen skin‐prick tests and serum IgE.

Role of Continuous Positive Airway Pressure Therapy on the Pathogenesis of Sleep-Related Frontal Lobe Epilepsy in a Child With Obstructive Sleep Apnea Syndrome

We describe an obese child with severe obstructive sleep apnea syndrome in whom nocturnal frontal lobe seizures developed within a week after therapy was started with continuous positive airway pressure. The video polysomnographic study after the onset of nocturnal episodes showed 3 seizures: 2 starting from slow-wave sleep when he was sleeping with continuous positive airway pressure, and 1 from stage 2 non—rapid eye movement sleep when he was sleeping without continuous positive airway pressure. Cyclic alternating pattern analysis during the video polysomnography recorded after the onset of nocturnal seizures disclosed a high cyclic alternating pattern rate during slow-wave sleep, and the recording obtained after antiepileptic therapy began showed a low cyclic pattern analysis rate. In this child, we describe the non—rapid eye movement sleep instability induced by continuous positive airway pressure therapy might have had a role in triggering the nocturnal seizures.

Detection of central and obstructive sleep apnea in children using pulse transit time

The aim of this study was to validate the use of pulse transit time (PTT) as a method to monitor sleep apnea in children. PTT was estimated as the interval between the ECGR-wave and the point at which the pulse wave at the finger reached 50% amplitude. First, we assessed changes in the PTT during breathing against known resistances in 15 awake children; resistance was applied with a modified nose and mouth two-way nonrebreathing face mask, having the inhalation valve port fitted with drilled plastic cylinders of various diameters. Second, we analyzed 20 events of obstructive apnea and 90 events of central apnea during sleep in 10 children. Our data showed good correlation between the inspiratory effort and PTT oscillation amplitude. In addition, PTT oscillation amplitude tuned out to successfully discriminate central from obstructive apnea.

Borna Disease Virus infection in children with psychiatric disorders

INTRODUCTIONIn the past 15 years the scientific communityhas observed a progressive change of paradigmabout psychiatric illness in adults and inchildren. Overall in the studies about mentaldiseases in children, Great emphasis was givento the mother-child relationship and to the fam-ily environment. Many studies have now sup-ported a change from a psychological view ofmental disorders to a more biological interpre-tation of psychiatry. The major contributionwas given by several studies about the geneticpredisposition of mental diseases, such asMajor Depression, Bipolar Disorder, ObsessiveCompulsive Disorder, and Attention Deficit/Hyperactive Disorder (ADHD). One of themost interesting hypothesis was suggesting thatbehavioural changes are the consequence ofviral infections. Herpes simplex virus seems tohave some relevance in the onset of schizo-phrenia (1), with a special affinity for poly-morphisms in MICB (2). These results providean intriguing hypothesis about a combinationof viral and genetic factors. Moreover severalreviews provide detailed information about Bor-na Disease Virus (BDV) infections in humans(3–5), which preferentially infect the nervoussystem being involved in neurological diseasesand in abnormal mental status. Data reported,ranged from high frequencies of BDV infectionto no BDV RNA in psychiatric patients, andfrom no significant level of BDV structural ele-