Agenesis of paranasal sinuses and nasal nitric oxide in primary ciliary dyskinesia.

Agenesis of paranasal sinuses has only been described in case reports of patients with primary ciliary dyskinesia (PCD). As agenesis of paranasal sinuses may contribute to low nasal nitric oxide levels, a common finding in PCD, we speculated that this condition might frequently occur in PCD patients. Patients referred for PCD evaluation were consecutively recruited for 30 months. In addition to standard diagnostic testing for PCD, a computed tomography (CT) scan of paranasal sinuses was performed in all subjects. 86 patients (46 children aged 8-17 yrs) were studied. PCD was diagnosed in 41 subjects and secondary ciliary dyskinesia (SCD) was diagnosed in the remaining 45 subjects. Frontal and/or sphenoidal sinuses were either aplastic or hypoplastic on CT scans in 30 (73%) out of 41 PCD patients, but in only 17 (38%) out of 45 with SCD (p = 0.002). There was a significant inverse correlation between the score for aplasia/hypoplasia of each paranasal sinus and nasal NO values in the PCD patients (p = 0.008, r = -0.432) but not in SCD (p = 0.07, r = -0.271). The findings of aplasia/hypoplasia of the frontal and or sphenoidal sinuses may be part of the spectrum of PCD and this finding should prompt exclusion of this condition.

Nasal nitric oxide and nitric oxide synthase expression in primary ciliary dyskinesia.

No study has evaluated the correlation between different expression of nitric oxide synthase (NOS) isoforms in nasal epithelial cells and nasal NO (nNO) level in primary ciliary dyskinesia (PCD). Gene expression of endothelial (NOS3) and inducible NOS (NOS2) and their correlation with nNO level, ciliary function and morphology were studied in patients with PCD or secondary ciliary dyskinesia (SCD). NOS3 gene polymorphisms were studied in blood leukocytes. A total of 212 subjects were studied (48 with PCD, 161 with SCD and three normal subjects). nNO level correlated with mean ciliary beat frequency (p = 0.044; r = 0.174). The lower the nNO level the higher was the percentage of immotile cilia (p<0.001; r = -0.375). A significant positive correlation between NOS2 gene expression and nNO levels was demonstrated in all children (p = 0.001; r = 0.428), and this correlation was confirmed in patients with PCD (p = 0.019; r = 0.484). NOS2 gene expression was lower in PCD than in SCD (p = 0.04). The NOS3 isoform correlated with missing central microtubules (p = 0.048; r = 0.447). nNO levels were higher in PCD subjects with the NOS3 thymidine 894 mutation, and this was associated with a higher ciliary beat frequency (p = 0.045). These results demonstrate a relationship between nNO level, NOS mRNA expression and ciliary beat frequency.

Health-related quality of life and unmet needs in patients with primary ciliary dyskinesia.

Few studies have evaluated the quality of life of patients with primary ciliary dyskinesia (PCD). We sought to determine the health impact of the disease as well as the unmet needs in a large group of patients. Questionnaires were either posted or e-mailed to known patients with PCD and published online. Questionnaires included the St George's Respiratory Questionnaire, the Medical Outcomes Study Short Form-36 and a questionnaire that we produced to obtain information on age of diagnosis, symptoms and likely PCD-specific problems of these patients. 78 subjects (96% of those invited) answered all the questionnaires. Patients were diagnosed at a mean age of 9.4 yrs. Progressive worsening of the disease was observed and adherence to physiotherapy was found to be poor, particularly in adolescents and adults. Patients with the highest treatment burden had a worse quality of life. Over time patients become progressively less interested in treating their disease and adherence to treatment modalities decreases. PCD is associated with a progressive and continuous impact on the physical and mental health of the patients. Earlier identification of the patients and better strategies aimed at improving compliance with care are urgently needed.

Simplified cell culture method for the diagnosis of atypical primary ciliary dyskinesia.

BACKGROUND: The diagnosis of primary ciliary dyskinesia (PCD) can be challenging, and it may be particularly difficult to distinguish primary ciliary disease from the secondary changes after infections. OBJECTIVES: The purpose of the study was to evaluate if nasal epithelial cells, obtained with nasal brushing instead of a biopsy, could be used in a culture system for the diagnosis of PCD in difficult cases. METHODS AND MAIN RESULTS: Ciliary motion analysis (CMA) and transmission electron microscopy (TEM) were performed on 59 subjects with persistent or recurrent pneumonia. These investigations allowed the diagnosis of PCD in 13 (22%) patients while the defect of the cilia was considered secondary to infections in 37 (63%) subjects. In the remaining nine (15%) patients the diagnostic evaluation with CMA and TEM remained inconclusive. Ciliogenesis in culture allowed the diagnosis of PCD in four of these patients, it was indicative of a secondary defect in two subjects, and it was not helpful in the remaining three patients. CONCLUSIONS: Culture of cells obtained with brushing of the nasal turbinate is not a perfect test, nevertheless it may offer diagnostic help in doubtful cases of PCD.

Bronchiectasis in children with recurrent pneumonia: an immunopathological damage associated with secondary ciliary dysmotility.

The aim of this study is to assess ciliary motion patterns in children with bronchiectasis unrelated to cystic fibrosis or primary ciliary dyskinesia. In 51 children with recurrent pneumonia, high resolution computed tomography (HRCT) was carried out to detect and score bronchiectasis. Moreover, ciliary ultrastructure, beat frequency and motion pattern were evaluated and compared to those observed in 30 healthy children. Bronchiectasis at HRCT was found in 31/51 children. Ciliary dysmotility was found in 20/31 children with bronchiectasis (64.5%). Overall, ciliary dysmotility was found in 39/51 patients (76.5%). Ciliary dysmotility showed a significant correlation with the HRCT score (p=0.02). Absent motion in some fields was found in 44/51 patients (86.3%) and this also showed significant correlation with the HRCT score (p=0.005). The specificity and sensitivity of ciliary dysmotility as an indicator of bronchiectasis was 74.3% and 83.3% respectively. The positive predictive value was 93.5%, and negative predictive value was 50%. Ciliary dysmotility, in children with recurrent airways infections, correlates with the presence and severity of bronchiectasis. Whether ciliary dysmotility is a cause or a consequence of anatomical lesion is a matter of speculation. Very likely there is an amplification and self-maintaining mechanism between the two events which may lead to more serious disease.

Airway response to a bronchodilator in healthy parents of infants with bronchiolitis.

In order to assess the role of genetic factors and environmental influences in bronchial responsiveness, we studied the airway response to an inhaled bronchodilator in 66 nonasthmatic parents (age, 30.9 +/- 5.9 years) of infants with bronchiolitis (group 1). It was a placebo-controlled double-blind study. A control group (group 2) of healthy parents of infants who did not have bronchiolitis also were investigated with the test of bronchodilator response. All subjects showed normal expiratory airflow and lung volumes (forced vital capacity [FVC], forced expiratory volume in 1 s [FEV1], and mean forced expiratory flow during the middle half of FVC [FEF25-75%] > 80 percent of predicted) at baseline forced expiratory maneuver. In 16 (24.2 percent) subjects of group 1, there was significant increase in at least one parameter after salbutamol administration, but not after placebo inhalation, with respect to baseline levels. Furthermore, no significant changes in FVC, FEV1, or FEF25-75% values were found in group 2. In conclusion, this study confirms that parents of infants with bronchiolitis have an enhanced airway responsiveness, greater than control parents. Further studies are needed to assess whether one may infer the outcome of infants with bronchiolitis from this characteristic in their parents.

Eosinophil cationic protein in infants with respiratory syncytial virus bronchiolitis: predictive value for subsequent development of persistent wheezing.

Infants with acute bronchiolitis during the first months of life are at increased risk of developing persistent wheezing and bronchial asthma later in life. The study of eosinophil cationic protein (ECP) suggests that eosinophil-related inflammatory mechanisms may play a role in respiratory syncytial virus (RSV) bronchiolitis. The aim of our study was to verify whether serum ECP (s-ECP) measurements are useful in predicting the development of persistent wheezing in children affected by RSV bronchiolitis during a 5 years follow-up period. Forty-eight infants were enrolled prospectively (mean age: 153.5 days). All had a clinical and radiological diagnosis of acute bronchiolitis and confirmed RSV infection. Peripheral eosinophil counts, levels of s-ECP, and serum IgE concentrations were measured during bronchiolitis. Five years later the children were re-evaluated in regard to their respiratory symptoms (standardized questionnaires) and atopic status (specific IgE levels). We observed significantly higher s-ECP levels (P < 0.001) at enrollment in subjects who developed persistent wheezing compared to subjects who did not show late wheezing. Initial s-ECP values allowed significant and correct prediction of persistent wheezing (P < 0.001). The risk to develop respiratory symptoms was 9.73 higher for infants with s-ECP levels > or = 8 microg/L than for those with s-ECP levels <8 microg/L (P < 0.0001). In conclusion, our study suggests that s-ECP levels in infants with bronchiolitis are useful in predicting the risk to develop wheezing in the subsequent 5 years.

Erosive immune complex-mediated arthritis associated with meningococcal meningitis.

A case of erosive sterile arthritis following meningococcal meningitis is described. High levels of immune complexes were detected in serum and synovial fluid. This is the first case in literature in which destruction of subchondral bone is documented. The erosion showed a progressive remineralization in the six months following clinical recovery.

[The asthmatic child and sports]. / Il bambino asmatico e lo sport.

Many asthmatic children are more disabled by exercise-induced asthma (EIA) than by other asthmatic attacks. Recent attention has focused on the pathophysiology of EIA and its prevention. Only within the past few years the effects of exercise programs have been examined carefully in children with asthma. Thus, they can increase work tolerance and fitness with a beneficial effect of physical training on EIA. Adequate training intensities would be possible if EIA could be prevented by premedication and if a type of exercise was chosen which gave good cardiopulmonary training. Although swimming is their optimum sport (experience of authors), asthmatic children should be encouraged to embrace a full and varied program of sport. Many sportsmen and women who have asthma are able to compete at the highest level and gain olympic and world honours.

[Yersinia enterocolitica septicemia in a girl with thalassemia major]. / Setticemia da Yersinia enterocolitica in bambina affetta da Thalassemia Major.

The Authors report the case of a child affected with Thalassemia Major who has presented a Yersinia Enterocolitica infection in a septicemial form. They point out that the clinical overture and its swift evolution with heart involvement make the diagnosis and the treatment difficult and, at the same time, urgent. They talk about the conditions which promote the septicaemia in this hemopathy.

[Lactate dehydrogenase isoenzymes and alveolar inflammation in acute severe bronchiolitis in infants]. / Isoenzimi della latticodeidrogenasi e flogosi alveolare nella bronchiolite acuta severa del lattante.

The authors have tried to value in 17 children (age: 1-11 months) affected by a severe acute viral bronchiolitis, if the measurement of Lactate Dehydrogenase (LD) isoenzymes could have been used to reveal alveolar injury. In the 76.4% (13/17) of subjects areas of consolidation were demonstrated by chest's radiographic examination due either to atelectasis secondary to obstruction or to inflammation of the alveoli. These coincided with a significant increase respect to a check's group (18 children) of LD4 in 70.5% (12/17), LD3 in 35.2% (6/17) and LD5 in 29.4% (5/17) of children. The presence of an analogous electrophoretic pattern and macrophages degenerated in pulmonary alveolar proteinosis lavage effluent associated with increases in lymphocytes and mononuclear phagocytes in lung specimens from children dead for bronchiolitis help to understand the inflammatory origin of pathological modification of LD isoenzymes observed in this series of cases.

[Initial experiences in the use of intravenous immunoglobulins in Guillain-Barré-Strohl syndrome]. / Prime esperienze sull'impiego delle immunoglobuline per via endovenosa nella sindrome di Guillain-Barré-Strohl.

The Authors demonstrate the successful therapeutic results obtained in two cases of Guillain-Barré-Strohl syndrome treated intravenously with high dosages of intact immunoglobulins. The possible immunological mechanisms behind this therapy are then discussed. The Authors believe that this treatment could very positively influence the prognosis of this disease.

[Lactate dehydrogenase isoenzymes in HIV-positive children]. / Gli isoenzimi della lattico-deidrogenasi nei bambini HIV-positivi.

Considering that in the HIV infection there is a precocious deterioration of humoral immunity with rapid turn-over of cellular B clones, we have evaluated the conduct of serum lactate-dehydrogenase activity (LD, EC 1.1.1.27) and its isoenzymes in 21 children born from HIV-positive mother respect to a control group (30 subjects). Furthermore we have checked the existence of a probable correlation between those and other clinical and immunologic parameters (total lymphocytes, CD4/CD8, immunoglobulins, classification according to the Atlanta CDC). In seropositive children we saw, respect to those evolved towards P3 stage, a significantly raising of LD4 (also vs. control group) for likely pulmonary parenchyma's damage, LD3 for B immature lymphocytes' increase and a reduction of LD1 (also vs. control group) for mature clones' decrement. Furthermore in seropositive subjects there was the existence of a direct correlation between LD1 and CD4/CD8 values. As such, the evaluation of LD isoenzymes can establish an useful element in the clinical monitoring of seropositive children.

[2 cases of cardial achalasia in childhood. Diagnostic aspects and therapeutic possibilities]. / Due casi di cardioacalasia in età pediatrica. Aspetti diagnostici e possibilità terapeutiche.

The authors present two case-studies of achalasia in infancy and the emphasize the rarity of the illness in this stage of life. They point out that a correct diagnosis requires a meticulous anamnesis which should be followed by a radiological, endoscopic and manometric study. The authors discuss their therapeutical experience with Nifedipine and they suggest that it should be used while waiting for surgery.

[Serum bile acids in the newborn: our experience]. / Gli acidi biliari serici nel neonato: nostra esperienza.

The study of bile acids in the newborn permits to the AA. to point out that the beginning of the feeding does not influence the "physiologic cholestasis" of the first days of life. Neonatal cholestasis is the expression of the immaturity of bile acids synthesis and hepatic and intestinal carriage, which is not correlated with the maternal conditions. Furthermore, the AA. discuss about the analogy between cholestasis and "physiologic hyperbilirubinemia", from which it differs for the longer time. In fact, the maturation of the enterohepatic circle occurs very slowly under possible dietetic factors influences.

[Lactate dehydrogenase and its isoenzymes in respiratory diseases in children]. / La latticodeidrogenasi ed i suoi isoenzimi nella patologia respiratoria del bambino.

Total Lactate Dehydrogenase (LD, EC 1.1.1.27) activity in serum and LD isoenzymes were quantified in 161 children (51 with pneumonia at the time of diagnosis, 60 hospitalized for asthma in acute period and 50 healthy subjects) to ascertain the relationship of these markers with injury of lung tissue. No statistical variations, between different groups in total activity, were found. Significantly decreased proportions of LD1 (p less than 0.000001) and of LD2 (p less than 0.000001) with simultaneous increase of LD4 (p less than 0.000001) and LD5 (p less than 0.000001) resulted in children with pneumonia, as to asthmatic or healthy subjects. Investigators conclude that LD should be determined in every patient with pneumonia because of the presence of a specific LD isoenzyme pattern.

CT-guided radiolabelled aerosol studies for assessing pulmonary impairment in children with bronchiectasis.

OBJECTIVE: To determine whether CT-guided mucociliary clearance studies allow differentiation between bronchiectasis associated with primary ciliary dyskinesia (PCD) and those unrelated to congenital or genetically transmitted defects. MATERIALS AND METHODS: Fifteen children aged 4-18 years with a CT diagnosis of bronchiectasis were included in the study. Six had PCD, while in nine cases no congenital disorder was demonstrated. RESULTS: CT showed bronchiectasis in 26 (29%) of 90 lung regions. Radiolabelled aerosol studies were conducted globally for each lung and on the regions affected by bronchiectasis. Global half-time of activity (t 1/2) values of patients with PCD were significantly higher (P < 0.001) than those with bronchiectasis unrelated to congenital disorders. Among the 26 lung regions in which CT demonstrated bronchiectasis, regional clearance was abnormal in 24 cases. Patients with PCD showed no statistically significant difference between regional and global t 1/2 values. Patients with bronchiectasis unrelated to congenital disorders showed significantly higher regional t 1/2 values in the affected regions with respect to the corresponding global pulmonary t 1/2 (P < 0.06). CONCLUSIONS: The combination of morphological CT information with functional data concerning the clearance of radiolabelled aerosol adds to our understanding of pulmonary impairment in children with bronchiectasis. In particular, regional studies allow the recognition of different mucociliary clearance patterns in bronchiectasis associated with PCD and those unrelated to congenital or genetically transmitted defects.