[Forced spirometry in healthy preschool children]. / Espirometría forzada en preescolares sanos bajo las recomendaciones de la ATS/ERS: estudio CANDELA.

INTRODUCTION: Reference values for spirometry in healthy preschool children have not yet been obtained in accordance with American Thoracic Society (ATS) and the European Respiratory Society (ERS) guidelines. The objective was to establish reference values for spirometry in healthy preschoolers under the ATS/ERS 2007 statement. MATERIAL AND METHOD: Children of at least 2 and under 7 years of age were tested in 9 pediatric pulmonary function laboratories. The technicians were trained to apply a standardized protocol to perform spirometry. RESULTS: Valid spirometry results were obtained in 455 (81.54%) out of 558 children: 242 boys (53.2%) and 213 girls (46.8%). Ages were as follows: 31 at least 2 and under 3 years old; 96, at least 3 and under 4; 108, at least 4 and under 5; 122, at least 5 and under 6 years, and 98, at least 6 and under 7 years. Formulas were used to calculate the reference values for all the spirometry variables in preschoolers. CONCLUSIONS: Spirometry is feasible in the majority of preschool children under the new guidelines. The availability of the reference values presented is an important step, both for the care of preschoolers and for further research on pulmonary function.

Antimicrobial therapy for pulmonary pathogenic colonisation and infection by Pseudomonas aeruginosa in cystic fibrosis patients.

Pseudomonas aeruginosa colonisation has a negative effect on pulmonary function in cystic fibrosis patients. The organism can only be eradicated in the early stage of colonisation, while reduction of bacterial density is desirable during chronic colonisation or exacerbations. Monthly, or at least 3-monthly, microbiological culture is advisable for patients without previous evidence of P. aeruginosa colonisation. Cultures should be performed at least every 2-3 months in patients with well-established colonisation, and always during exacerbations or hospitalisations. Treatment of patients following the first isolation of P. aeruginosa, but with no clinical signs of colonisation, should be with oral ciprofloxacin (15-20 mg/kg twice-daily for 3-4 weeks) plus inhaled tobramycin or colistin (intravenous treatment with or without inhaled treatment can be used as an alternative), while patients with acute infection should be treated for 14-21 days with high doses of two intravenous antimicrobial agents, with or without an inhaled treatment during or at the end of the intravenous treatment. Maintenance treatment after development of chronic P. aeruginosa infection/colonisation (pathogenic colonisation) in stable patients (aged>6 years) should be with inhaled tobramycin (300 mg twice-daily) in 28-day cycles (on-off) or, as an alternative, colistin (1-3 million units twice-daily). Colistin is also a possible choice for patients aged<6 years. Treatment can be completed with oral ciprofloxacin (3-4 weeks every 3-4 months) for patients with mild pulmonary symptoms, or intravenously (every 3-4 months) for those with severe symptoms or isolates with ciprofloxacin resistance. Moderate and serious exacerbations can be treated with intravenous ceftazidime (50-70 mg/kg three-times-daily) or cefepime (50 mg/kg three-times-daily) plus tobramycin (5-10 mg/kg every 24 h) or amikacin (20-30 mg/kg every 24 h) for 2-3 weeks. Oral ciprofloxacin is recommended for patients with mild pulmonary disease. If multiresistant P. aeruginosa is isolated, antimicrobial agents that retain activity are recommended and epidemiological control measures should be established.

Budesonide/formoterol in a single inhaler versus inhaled corticosteroids alone in the treatment of asthma.

The aim of this study was to evaluate the efficacy (expressed as effect on lung function) and tolerability of Symbicort (budesonide/formoterol in a single inhaler) in children with asthma. This was a double-blind, double-dummy, randomized, parallel-group, multicenter trial. After a 2-4-week run-in period, 286 asthmatic children (177 boys, 109 girls; mean age, 11 years; mean forced expiratory volume in 1 sec (FEV(1)), 75% predicted normal), previously treated with inhaled corticosteroids (average dose 548 microg/day), were randomized to 12 weeks' treatment with either budesonide/formoterol 80/4.5 microg, two inhalations twice daily (n = 148), or an equivalent dose of budesonide 100 microg, two inhalations twice daily (n = 138). Efficacy variables included morning and evening peak expiratory flow (PEF), spirometery, asthma symptoms, and use of rescue medication (beta(2)-agonists). Serial FEV(1) assessments were carried out on a subgroup of children (budesonide/formoterol, n = 41; budesonide, n = 40) at randomization and at week 12. Relative to baseline, morning PEF (primary variable) increased to a significantly greater extent with budesonide/formoterol than with budesonide alone (7.22% predicted normal vs 3.45% predicted normal; P < 0.001). Evening PEF also increased significantly with budesonide/formoterol (6.13% predicted normal vs. 2.73% predicted normal; P < 0.001), as did mean FEV(1) and serial FEV(1) measured over 12 hr (both P < 0.05). Similar improvements in asthma symptoms and rescue medication use were observed in both groups. The two treatment groups were similar in terms of their adverse-event profile and rates of discontinuation. Budesonide/formoterol in a single inhaler provided rapid improvements in PEF and FEV(1) compared to inhaled budesonide alone. These improvements were sustained throughout the study period. Budesonide/formoterol was well-tolerated in children with moderate persistent asthma.

Lung transplantation in young infants with interstitial pneumonia.

OBJECTIVES: We describe our experience with infants suffering from interstitial pneumonia referred for lung transplantation. METHODS: From April 1998 to December 2000, three infants were admitted to our lung transplantation program: a 9-month-old girl (patient 1) suffering from surfactant protein C deficiency who had high oxygen requirements (fraction of inspired oxygen: 70% to 90%), and two boys, ages 2 (patient 2) and 9 months (patient 3), who were ventilator-dependent due to chronic pneumonitis of infancy. RESULTS: Patients were transplanted at the age of 5 months (patient 2) and 13 months (patients 1 and 3) at 87 to 105 days after being accepted for lung transplantation. All cases underwent a sequential double lung transplant on cardiopulmonary bypass. The immunosuppressive regime included tacrolimus, prednisone, and azathioprine. Patients 2 and 3 also received basiliximab. Two cases suffered a mild rejection episode that responded to high-dose steroids. Patient 2 was ventilator-dependent for 8 months after transplant, owing to severe bronchomalacia and left main bronchus stenosis. Bronchial stenosis resolved after pneumatic dilatation and endobronchial stenting. This patient also presented with a pulmonary artery anastomosis stricture that required percutaneous balloon dilatation. All three patients are at home, carrying out normal activities for their age, with no respiratory symptoms after a period of 8 to 29 months of follow-up. CONCLUSIONS: Interstitial pneumonia of infancy is a rare disease with a bad prognosis and no specific treatment; therefore, lung transplantation represents a good therapeutic option for these infants.

Enhanced oxidative damage in cystic fibrosis patients.

Antioxidant depletion and increased free radical production by inflammatory cells have been described in cystic fibrosis (CF) patients. To evaluate oxidative damage intensity, we measured plasma concentrations of malondialdehyde, hydroperoxides and protein carbon groups as markers of oxidative injury to lipids and proteins in a group of 101 CF patients free of acute exacerbation, and in 43-112 controls. Moreover, we estimated antioxidant function by measuring activities of erythrocyte superoxide dismutase, glutathione reductase and vitamin E concentrations. In CF patients, malondialdehyde and hydroperoxide plasma levels were significantly higher than in controls (p < 0.001). Increased lipid peroxidation was documented by these two markers. Parallel rises in protein carbonyls in plasma of CF patients were observed (p < 0.0001). These patients presented biochemical but not clinical vitamin E deficiency. Glutathione reductase and superoxide dismutase activities were significantly higher than in controls. These results show a serious imbalance of CF patients between oxidant-antioxidant status leading to oxidative stress.

[Intravascular hemolysis following percutaneous occlusion of the ductus arteriosus]. / Hemólisis intravascular tras el cierre percutáneo del conducto arterioso.

Transcatheter occlusion of patent ductus arteriosus has become a safe and successful technique, but it's not free of complications. We present the case of a two-year-old boy who underwent routine transcatheter closure of his patent ductus arteriosus, using a "coil" device. Twenty hours later he developed severe persistent hemolysis in association with residual ductal flow. Patient's clinical situation became stable when the device was removed. Pulmonary embolization of the device and hemolysis are the main complications of percutaneous closure of the patent ductus arteriosus. Hemolysis occurs rarely (0.5%) and is always associated with the presence of residual ductal flow. Several approaches to this problem have been described. Mild cases may require no intervention; however, when severe hemolysis is present, removal of the device may be needed, proceeding with surgical repair of the patent ductus arteriosus.

[Pilot study on knowledge about asthma and its treatment among Spanish teachers]. / Estudio piloto de los conocimientos sobre el asma y su tratamiento entre los educadores españoles.

UNLABELLED: This was a study aimed to know the knowledge about asthma. SUBJECTS AND METHOD: 933 teachers of 27 schools from 7 cities (children aged between 4 and 15 years) using a self-administered questionnaire Half of them knew asthma prevalence and its hereditary nature. Nearly all related asthma with allergy, 38% with exercise, 25%had students who suffered from asthma attacks in the school, and 91% admitted to have limited information and wish to improve it. CONCLUSION: Our survey reveals that Spanish teachers have a limited information about asthma.

[Changes in the pancreatic and respiratory functions in cystic fibrosis. The influence of the time of the evolution of the disease]. / Alteración de la función pancreática y respiratoria en la fibrosis quística. Influencia del tiempo de evolución de la enfermedad.

BACKGROUND: Cystic fibrosis is the most frequent congenital disease in Caucasian and is transmitted by recessive autosomic inheritance. It is characterized by affection of different glands of exocrine secretion, particularly the pancreas and the lung. The aim of this study was to analyze the degree of alteration of pulmonary and pancreatic exocrine function in a group of patients with cystic fibrosis in relation to the time of disease evolution. METHODS: Twenty-one patients between 9 and 31 years of age were studied; 11 with an evolution of lower than or equal to 158 months and 10 with an evolution of higher than 158 months (median of the total patients). To study pancreatic exocrine function the BT-PABA test immunoreactive serum trypsin test were used. To evaluate respiratory function FEV1, FVC, FEV1/FVC ratio and PaO2 were used. RESULTS: The results obtained demonstrated that in the group with a lower time of evolution the diagnosis had been carried out at earlier ages (17 +/- 17 months versus 84 +/- 60 months; p = 0.002) and presented a significantly more altered pancreatic exocrine function (BT-PABA: 13 +/- 12% versus 35 +/- 23%; p = 0.013). However, respiratory function was altered in the group with longer time of evolution (FEV1: 68 +/- 20% versus 36 +/- 23%; p = 0.003; FVC: 74 +/- 9 versus 52 +/- 25%; p = 0.013; FEV1/FEV: 77 +/- 19 versus 50 +/- 9%; p < 0.001; PaO2: 84 +/- 16 versus 58 +/- 11%; p < 0.001). CONCLUSIONS: Pancreatic exocrine function is most intensely affected in patients diagnosed with cystic fibrosis at earlier and with shorter times of evolution while patients who have the longest time of evolution and who were diagnosed later in life presented greater changes in respiratory function.

[Validity of the Spanish version of the Pediatric Quality of Life Questionnaire for evaluating quality of life in asthmatic children]. / Validación de la versión española del Pediatric Quality of Life Questionnaire en la valoración de la calidad de vida del niño asmático.

BACKGROUND: To analyze the clinical utility of the quality of life questionnaire for asthmatic children (PAQLQ) and to validate it for use in clinical practice. PATIENTS AND METHOD: 1,012 children between 6 and 14 years of age, with a diagnosis of mild to moderate asthma attending 48 Spanish hospitals were included in the study. The patients' socio-demographic and clinical characteristics were recorded and all patients were administered the PAQLQ and EQ-5D questionnaires on two occasions: at the baseline visit and at 2-3 months from baseline in patients with uncontrolled asthma(group A) and at baseline and 15 days from baseline in patients with controlled asthma (group B). The feasibility, validity, reliability and sensitivity to change of the PAQLQ were assessed. RESULTS: The PAQLQ proved to be feasible for use in children over 7 years of age with mild or moderate asthma. The PAQLQ did not show a statistically significant relationship with socio-demographic variables, nor with the majority of clinical variables, with the exception of asthma severity, number of exacerbations, symptoms and use ofon- demand short-term beta2 agonist drugs. Correlations between PAQLQ and EQ-5D dimensions were strongest between dimensions measuring similar attributes. Cronbach's *coefficients for the PAQLQ ranged from 0.88 for the limitations in activities dimension to 0.96 for the overall score. The intraclass correlation coefficient for PAQLQscores in group B ranged from 0.71 (limitation of activities)to 0.83 (overall score). The effect size between both visits ranged from 0.49 to 0.69. CONCLUSIONS: The Spanish version of the PAQLQ proved to be valid for use in children with mild to moderate asthma.

[Bone mass in patients with cystic fibrosis of the pancreas. Relationship with anthropometric parameters and genotype]. / Masa ósea en pacientes con fibrosis quística de páncreas. Relación con parámetros antropométricos y genotipo.

BACKGROUND: Cross-sectional study of bone mineral density (BMD) in children and adolescents with cystic fibrosis of the pancreas. The relationship of BMD values with nutritional status, respiratory function and the cystic transmembrane regulator genotype was also evaluated. PATIENTS AND METHODS: BMD expressed as grams of hydroxyapatite/cm2 was measured by dual-energy X-ray absorptiometry in the lumbar spine (L2-L4) in 41 patients (21 males and 20 women; age range: 4-21 years) with cystic fibrosis of the pancreas and compared with that of 471 normal controls (256 males and 215 women; age range: 1-20 years). Twenty patients were prepubertal, 9 pubertal and 12 young adults. RESULTS: Clinical repercussion of the disease evaluated by clinical and anthropometric data (weight, height and body mass index) and respiratory function was considered moderate. Height z score (mean [MSE]) was -0.53 (0.28), weight -0.81 (0.21) and body mass index -0.82 (0.12) BMD z score values (mean [MSE]) were -1.14 (0.17) and differed significantly (p < 0.001) from those of normal age- and sex-matched controls. No significant differences were observed between males and women or among prepubertal, pubertal and young adult patients. BMD z score values less than-1 z score were found in 53% and under -2 z score in 8%. Cystic transmembrane regulator genotype was studied in 36 patients (17 were F508/-, 10 F508/F508, 5 G542X/- and 4 diverse) and did not predict bone mineral status. A statistically significant correlation was found between BMD z score values and height z score, weight z score, body mass index z score and clinical assessment according to Shwachman criteria. A negative and statistically significant correlation was observed between BMD z score and functional score. CONCLUSIONS: The decrease in BMD values in CF patients begins early in life and appears to be related to the degree of clinical expression of the disease.

[Comparative efficacy of oral deflazacort versus oral prednisolone in children with moderate acute asthma]. / Estudio comparativo de la eficacia del deflazacort frente a prednisolona en el tratamiento de la crisis asmática moderada.

OBJECTIVES: To assess the efficacy and tolerability of oral deflazacort versus oral prednisolone in acute moderate asthma in children. PATIENTS AND METHODS: We performed a prospective, randomized, parallel group trial of children aged 6 to 14 years old with a diagnosis of asthma who presented to the pediatric emergency department for moderate asthma exacerbation. All patients were administered short-acting beta2-adrenergic agonists. The intervention groups received either oral deflazacort (1.5 mg/kg) or prednisolone (1 mg/kg) for 7 days. The primary outcome measure was forced expiratory volume in 1 second (FEV1) and secondary outcome measures were pulmonary symptom score index, peak expiratory flow rate (PEFR), hospitalization rate and the use of rescue beta2-agonists. Patients were evaluated at the start of treatment (visit 1), on day 2 (visit 2) and on day 7 (visit 3). RESULTS: Of the 54 children enrolled, two were hospitalized on visit 2 (one from each group). Baseline clinical data were similar in both groups: FEV1: 53 and 51 %; bronchodilator test: 119 and 121 %; PEFR: 169 and 165 L/min; symptom score: 6 and 6.5 for the deflazacort and prednisolone groups, respectively. On visit 2, all measures improved: FEV1: 122.2 and 126.5 % (p < 0.05); PEFR: 164 and 149 L/min (p < 0.05); symptom score: -4.4 and -3.8 (p < 0.05), without significant differences between groups. On visit 3 all variables continued to show improvement: FEV1: 133.2 and 132.5 % (p < 0.05); PEFR: 1115.7 and 187.6 L/min (p < 0.05); symptom score: -5.4 and -5.9 (p < 0.05), without significant differences between groups. No adverse effects were reported. CONCLUSIONS: Deflazacort and prednisolone show similar efficacy in improving pulmonary function and in producing clinical improvement in the management of acute moderate asthma in children.

[Our experience in the treatment of cervico-facial adenitis caused by non-tuberculous mycobacteria (atypical mycobacteria)]. / Nuestra experiencia en el tratamiento de las adenitis cervicofaciales por micobacterias no tuberculosas (micobacterias atípicas).

The authors believe that the greater part of chronic cervicofacial adenitis actually observed in our hospitals, are not caused by M. tuberculosis or M. bovis but by scrofulaceum mycobacterium, M. avium, M. fortuitum and M. Kansasii, and above all, by the first two of these. They present their experience with 16 cases of cervico-facial adenitis due to atypical mycobacterium (CAAM) treated in our centre during the last years, in which period no case of cervical tuberculosis (CT) was observed. It is important to establish an early differential diagnosis between both etiologies, seeing as treatment is different. Whilst tuberculostatics can solve the phymic infection, surgical extirpation is the only solution for CAAM. The diagnosis of these types of infection is achieved by means of a very characteristic clinical procedure and by cutaneous tests specific for each bacteria. Faced with the clinical suspicion, the total extirpation should be effected of the adenopathic block affected. The exact diagnosis can only be made by the culture of the operatory mass.

Development and validation of a questionnaire to assess asthma control in pediatrics.

OBJECTIVE: To develop and validate a questionnaire to assess asthma control in children (CAN). DESIGN: Two versions of the CAN (for carers and children) were developed. Both versions were validated in an observational, prospective, multicenter study performed in 38 hospital outpatient clinics throughout Spain. Four hundred fifteen patients and their carers agreed to participate. Of these, 414 patients under 14 years old with frequent episodic or persistent (moderate to severe) asthma completed the questionnaire on 3 occasions (baseline, week 2, and week 12). For patients aged 2-8 the questionnaire was only completed by the carers, but for patients aged 9-14 the questionnaire was completed by the carers and the children. Clinician ratings of asthma control were used as a gold standard to assess the sensitivity, specificity, PPV and NPV of the new measure. RESULTS: Evaluable responses were obtained from 215 carers for children aged 2-8 years and 199 children aged 9-14 years, and their parents. Using a questionnaire total score cut-off of 8 the patient version had a sensitivity of 76.3% and a specificity of 62.9%. For carer version these values were 73% and 69.7%, respectively. A cut point of 8 was selected to maximize the screening accuracy of the CAN questionnaire. Effect sizes in patients with clinician-rated improvements in asthma control were 0.33 and 0.57 for the carer and child versions, respectively. CONCLUSIONS: The screening accuracy and validity of the CAN questionnaire make it suitable for use in research and clinical practice. The sensitivity and specificity were close to 70%, which is acceptable for the study objective: obtain a tool to measure the level of asthma control.

Upregulation of COX-1 and COX-2 in nasal polyps in cystic fibrosis.

BACKGROUND: Since abnormalities in prostanoid metabolism occur in the lower airway of patients with cystic fibrosis (CF), it is likely that they could also be detected in the nose. METHODS: The degree of mRNA and protein expression of cyclo-oxygenase (COX) enzymes 1 (COX-1) and 2 (COX-2) was examined using quantitative reverse competitive polymerase chain reaction (RT-PCR) and Western blot analysis in the nasal polyps from 10 patients with CF, nasal polyps from 10 non-CF patients and 11 nasal mucosa specimens. The results are presented as 10(6) cDNA molecules/mug total RNA and the densitometric ratio between protein and beta-actin. RESULTS: COX-1 mRNA levels were significantly higher in CF nasal polyps (median 2.34, 25-75th percentiles 1.6-3.2) than in the nasal mucosa (0.78, 0.11-1.21), while there was no difference with non-CF nasal polyps (1.11, 0.80-3.15). COX-1 protein levels were significantly higher in CF nasal polyps (3.63, 2.71-4.27) than in nasal mucosa (1.55, 0.66-2.33) and non-CF nasal polyps (2.19, 1.72-3.68). COX-2 mRNA was significantly higher in CF nasal polyps (3.34, 2.42-7.05) than in nasal mucosa (1.69, 0.19-3.50). No differences were found in COX-2 mRNA expression between CF and non-CF polyps (1.38, 0.12-6.07). COX-2 protein levels were also significantly higher in CF nasal polyps (0.23, 0.04-0.34) than in non-CF nasal polyps (0.011, 0.009-0.016) or nasal mucosa (0.014, 0.014-0.016). CONCLUSIONS: Upregulation in the expression of COX-1 and COX-2 could explain the high production of prostanoids reported in CF. These findings raise questions regarding the potential use of selective or non-selective COX-2 non-steroidal anti-inflammatory treatment in CF.

[Bacteriology of mucoviscidosis during a 5-year period]. / Bacteriología de la mucoviscidosis durante un período de 5 años.

BACKGROUND: We have studied the bacteriology of mucoviscidosis cases from 1985 to 1989. MATERIAL: A total of 336 samples from 50 patients (median age: 7 year, range: 1 day-18 years) with mucoviscidosis were studied. RESULTS: The most frequently isolated microorganisms was Pseudomonas aeruginosa (59.2%), followed by Staphylococcus aureus (19%) and Haemophilus influenzae (18.4%). In patients younger than 1 year of age other different microorganisms were identified in 61.1% of cases, but S. aureus (11.1%) and Pseudomonas aeruginosa (5.5%) were also isolated. The incidence of Pseudomonas cepacia (0.6%) is low in our environment. We did not isolate any Legionella sp. strain.

Uniparental inheritance of microsatellite alleles of the cystic fibrosis gene (CFTR): identification of a 50 kilobase deletion.

More than 250 mutations have been detected in the cystic fibrosis (CF) transmembrane regulator (CFTR) gene, most of which are single point mutations or small deletions or insertions of a few nucleotides. Here we report the first large deletion identified in the CFTR gene, which involves 50 kb in two stretches of DNA: one of 10 kb from exon 4 to exon 7, and another of 40 kb, spanning exons 11 to 18. The deletion has been detected via uniparental inheritance of CFTR microsatellite alleles (IVS17BTA and IVS17BCA) in 3 independent CF families. Clinical status of the 3 CF patients, of which two have the delta F508 mutation as the other CF allele, suggests that this mutation is responsible for a severe clinical phenotype, indistinguishable from homozygous delta F508 patients. The deletion detected here suggests that other large, but less complex molecular defects could also exist in the CFTR gene.

[Metabolic and renal changes in lymphoproliferative syndromes of childhood]. / Alteraciones metabólicas y renales en los síndromes linfoproliferativos de la infancia.

Authors report five patients with lymphoproliferative diseases who suffered from metabolic and renal disorders hyperuricemia, hyperphosforemia, hyperkaliemia, hypocalcemia and azotemia) during initial phase of chemotherapy. They comment on measures to prevent these disorders and the need of hemodialysis in some cases.