The aim of the study was to assess short-term repeatability of measurements of fractional exhaled nitric oxide (FENO) and its correlates in children in the 6- to 9-year age bracket participating in a respiratory epidemiological survey. FENO was measured in two sessions one week apart in 101 children. Participants were divided into three groups: asymptomatic (n = 76); symptomatic (n = 14); and asthma (n = 11). Absolute and relative differences between the measurements, as well as concordance correlation coefficients, were used in order to assess repeatability. The two FENO measurements were strongly correlated (0.98). Although intragroup comparisons of the two measurements were not significantly different (p = 0.2), intergroup comparisons were. FENO measurements are reproducible in children in epidemiological settings.

Keywords: Nitric oxide; Exhalation; Asthma.

This paper reviews in brief the role of nitric oxide in the respiratory physiology and in the pathology of some pulmonary diseases. The potential diagnostic and monitoring uses in several clinical situations are also discussed.

Keywords: respiratory tract diseases; lung diseases, obstructive; asthma; smoking; cystic fibrosis; bronchiectasis lung; lung transplantation

Nitric oxide (NO) is an endogenous vasoactive compound that contributes to pulmonary vascular homeostasis and is produced by three nitric oxide synthase (NOS) isoforms-neuronal NOS (nNOS); inducible NOS (iNOS); and endothelial NOS (eNOS)-all three of which are present in the lung. Studies using pharmacological inhibitors or knockout mice have shown that eNOS-derived NO plays an important role in modulating pulmonary vascular tone and attenuating pulmonary hypertension. However, studies focusing on the role of iNOS have shown that this isoform contributes to the pathophysiology of acute lung injury and acute respiratory distress syndrome. This review aimed at outlining the role played by NO in the control of pulmonary circulation, both under physiological and pathophysiological conditions. In addition, we review the evidence that the L-arginine-NO-cyclic guanosine monophosphate pathway is a major pharmacological target in the treatment of pulmonary vascular diseases.

Keywords: Nitric oxide; Arginine; Nitric oxide synthase; Cyclic GMP; Pulmonary circulation.

The objective of this paper is to report some clinical and therapeutic aspects of inhaled nitric oxide in pediatrics. Some references were obtained from Medline® using the keywords: inhaled nitric oxide and pediatrics, and critical care. Other sources were the University library and personal files. Along the last decade, clinical trials with inhaled nitric oxide demonstrated only a few specific areas of proven efficacy and a variety of possible adverse events. Toxicity related to inhaled nitric oxide included metahemoglobinemia, cytotoxic pulmonary effects, excess production of nitrogen dioxide and peroxynitrite, and injury to the pulmonary surfactant system. The administration of inhaled nitric oxide to patients with severe left ventricular dysfunction and pulmonary hypertension should be cautious, since vasodilatation may increase pulmonary blood flow and lead to excessive preload. Some studies showed the clinical effects related to abrupt nitric oxide withdrawal, including rebound pulmonary hypertension. Current literature supports the therapeutic use of inhaled nitric oxide in persistent pulmonary hypertension of the newborn (gestational age ³ 34 weeks) to improve oxygenation and avoid extracorporeal oxygenation; and in congenital cardiopathy accompanied by pulmonary hypertension, especially in the immediate postoperative period. To date, research in pediatrics and multicentre trials in adults with inhaled nitric oxide therapy have failed to show mortality reduction or decrease the amount of time under mechanical ventilation for acute respiratory distress syndrome and acute lung injury. This indication needs further investigations. Persistent pulmonary hypertension is the most important indication for inhaled nitric oxide. The Food and Drug Administration has not approved inhaled nitric oxide in acute respiratory distress syndrome for adults and children.

Keywords: Nitric oxide/therapeutic use. Pediatrics. Pulmonary hypertension. Critical care.

Objective: To evaluate the association between nutritional status measurements and pulmonary function in children and adolescents with cystic fibrosis. Methods: We evaluated the nutritional status of 48 children and adolescents (aged 6-18 years) with cystic fibrosis based on body mass index (BMI) and body composition measurements-mid-arm muscle circumference (MAMC) and triceps skinfold thickness (TST)-at a referral center in the city of Rio de Janeiro, Brazil. Pulmonary function was assessed by means of spirometry, using FEV1 to classify the severity of airway obstruction. We used Student's t-tests for comparisons between proportions and linear regression analysis for associations between continuous variables. The level of significance was set at p < 0.05. Results: The evaluation of nutritional status based on BMI identified a smaller number of malnourished patients than did that based on MAMC (14 vs. 25 patients, respectively). Most of the patients presented mild pulmonary disease. Mean FEV1 was 82.5% of predicted. Pulmonary function was found to correlate significantly with BMI, MAMC and TST (p = 0.001, p = 0.001 and p = 0.03, respectively). All subjects with moderate or severe pulmonary involvement were considered malnourished based on BMI and body composition parameters. Of the 25 patients considered malnourished based on body composition (MAMC), 19 were considered well-nourished based on their BMI. Conclusions: In the present study, all nutritional status measurements correlated directly with the pulmonary function of children and adolescents with cystic fibrosis. However, body composition measurements allowed earlier detection of nutritional deficiencies.

Keywords: Cystic fibrosis; Body composition; Spirometry; Nutrition assessment.

Objective: To measure exhaled carbon monoxide (COex) levels in smokers with and without COPD. Methods: Smokers treated at outpatient clinics of São Lucas Hospital in the city of Porto Alegre, Brazil, between September of 2007 and March of 2009 were invited to participate in this study. The participants completed a questionnaire regarding demographic and epidemiologic characteristics and were submitted to spirometry, as well as to determination of COex and urinary cotinine levels. The participants were divided into two groups: those with COPD and those without COPD. Results: The study involved 294 smokers, of whom 174 (59.18%) had been diagnosed with COPD. All of the participants presented with urinary cotinine levels > 50 ng/mL. Smokers with COPD presented significantly higher median values for age and pack-years than did those without COPD (p < 0.001 and p = 0.026, respectively). No other statistically significant differences were found. When adjusted for gender, age at smoking onset, number of cigarettes/day and urinary cotinine level, the mean values of COex were higher, but not statistically so, in the COPD group than in the non-COPD group (17.8 ± 0.6 ppm and 16.6 ± 0.7 ppm, respectively; p = 0.200). The differences remained nonsignificant when plotted logarithmically. A wide dispersion of COex values was found when the participants were classified by FEV1 level (r = −0.06; p = 0.53) or by Global Initiative for Chronic Obstructive Lung Disease classification (r = 0.08; p = 0.34). The proportions of false-negative results for smoking were 18.4% and 6.7%, respectively, in the COPD and non-COPD groups (p = 0.007). Conclusions: Since COex values did not differ significantly between smokers with COPD and those without, there seem to be no major contraindications to their use in smokers with COPD.

Keywords: Carbon monoxide; Smoking cessation; Pulmonary disease, chronic obstructive.

Objective: To determine the rate at which satisfactory spirometry results are obtained (spirometry success rate) in preschool children. Methods: We analyzed the spirometry results of children ≤ 6 years of age. All tests were conducted between June of 2009 and February of 2010 in the Pulmonary Function Laboratory of the Hospital Infantil Jeser Amarante Faria, located in the city of Joinville, Brazil. The spirometry program employed features an animated incentive (soap bubbles). The procedures were performed by a pediatric pulmonologist, in accordance with the reproducibility and acceptability criteria recommended by the American Thoracic Society. We attempted to achieve an expiratory time of at least 1 s. The following parameters were measured: FVC, FEV0.5, FEV1, and the FEV1/FVC ratio. Results: Our sample comprised 74 children. The spirometry success rate was 82%. Although the performance improved with age, the difference between younger and older children was not significant (p > 0.05). An average of 6.6 attempts/test were needed in order to achieve acceptable, reproducible curves. All 61 successful tests produced satisfactory FEV0.5 and FEV1 values. By calculating Z scores, we found that 21.6% of the children presented with an obstructive pattern. Conclusions: In our sample, the spirometry success rate was high, showing that spirometry is a valid method for assessing pulmonary function in preschool children. The high success rate in our sample might be attributable to the use of an incentive and to the fact that the tests were performed by professionals specializing in pediatrics.

Keywords: Spirometry; Feasibility studies; Respiratory function tests.

In recent years, the analysis of exhaled breath condensate samples has been given great weight as a noninvasive methodology of studying physiology and lung diseases. The present study describes a device for measuring exhaled breath condensate that is affordable, easily constructed, portable and suitable for use in the field, as well as allowing the collection of simultaneous samples. The results obtained with this device in terms of the concentrations of pH, hydrogen peroxide and nitrite, metabolites related to inflammatory and oxidative damage, in exhaled breath condensate samples are comparable to those obtained with other devices previously described.

Keywords: Exhalation; Lung diseases; Equipment design.

Objective: To evaluate whether the exhaled breath temperature (EBT), measured by a noninvasive method, is an effective means of monitoring patients with uncontrolled asthma. Methods: A pilot study comprising nine patients (seven women and two men; mean age: 39 years) diagnosed with asthma at least one year prior to the beginning of the study and not having been under maintenance therapy for the last three months. In the first visit, the patients underwent spirometry and measurement of EBT. The patients were then instructed to use inhaled budesonide/formoterol (200/6 µg) every 12 h for six weeks. In addition, the patients with severe asthma (FEV1 < 60% of predicted) were instructed to use oral prednisolone (40 mg/day) for five days. After six weeks, the patients underwent the same tests. Results: All of the patients reported an improvement in the symptoms of asthma, as confirmed by a statistically significant increase in FEV1 from the first to the second visit (mean, 56.1% vs. 88.7% of predicted; p < 0.05). Five patients used oral prednisolone for the first five days of the treatment period. Six patients used additional doses of inhaled budesonide/formoterol (mean duration, 2.5 weeks). The EBT decreased significantly from the first to the second visit (mean EBT: 35.1°C vs. 34.1°C; p < 0.05). Conclusions: Uncontrolled asthma, especially during exacerbations, is followed by an increase in EBT, which decreases after appropriate asthma control, as demonstrated by an increase in FEV1 and an improvement of the reported symptoms. These preliminary results suggest that EBT can be used as a parameter for the assessment of asthma control.

Keywords: Asthma; Biomarkers, pharmacological; Hydroxycorticosteroids.

We aimed to investigate the effects of age and gender on the profile of exhaled volatile organic compounds. We evaluated 68 healthy adult never-smokers, comparing them by age and by gender. Exhaled breath samples were analyzed by an electronic nose (e-nose), resulting in "breathprints". Principal component analysis and canonical discriminant analysis showed that older subjects (≥ 50 years of age) could not be distinguished from younger subjects on the basis of their breathprints, as well as that the breathprints of males could not distinguished from those of females (cross-validated accuracy, 60.3% and 57.4%, respectively).Therefore, age and gender do not seem to affect the overall profile of exhaled volatile organic compounds measured by an e-nose.

Keywords: Breath tests; Volatile organic compounds; Electronic nose.

Objective: To investigate the symptoms most frequently found in children with a polysomnographic diagnosis of obstructive sleep apneahypopnea syndrome (OSAHS). Methods: We evaluated 38 children consecutively referred to the sleep laboratory with suspicion of OSAHS between June of 2003 and December of 2004. The patients were submitted to a pre-sleep questionnaire and to polysomnography. Results: The mean age was 7.8 ± 4 years (range, 2-15 years), and 50% of the children were male. Children without apnea accounted for 7.9% of the sample. The obstructive sleep apnea observed in the remainder was mild in 42.1%, moderate in 28.9% and severe in 22.1%. Severe cases of apnea were most common among children under the age of six (pre-school age). In children with OSAHS, the most common symptoms were snoring and nasal obstruction, which were observed in 74.3 and 72.7% of the children, respectively. Excessive sleepiness and bruxism were seen in 29.4 and 34.3%, respectively, and reflux disease was seen in only 3.1%. Restless legs and difficulty in falling asleep were identified in 65 and 33%, respectively. All of the children diagnosed with severe OSAHS also presented snoring and bruxism. Conclusions: Snoring and nasal obstruction were the most common symptoms found in our sample of children and adolescents with OSAHS. In addition, OSAHS severity was associated with being in the lower age bracket.

Keywords: Obstructive sleep apnea; Polysomnography; Pediatrics; Snoring.

Objective: To identify socioeconomic factors and clinical factors associated with the development of complications in preschool children hospitalized with community-acquired pneumonia (CAP). Methods: This was a prospective longitudinal study involving children (12-59 months of age) diagnosed with CAP and admitted to the pediatric wards of two hospitals in the metropolitan area of Campinas, Brazil. Children with cystic fibrosis, heart disease, pulmonary malformations, neurological disorders, or genetic diseases were excluded. The diagnosis of CAP was based on clinical and radiological findings. Data were collected from the medical records and with a semi-structured questionnaire. The subjects were divided into two groups (complicated and uncomplicated CAP). Socioeconomic and clinical variables were compared, and multivariate logistic regression analysis was performed. Results: Of the 63 children included, 29 and 34, respectively, presented with uncomplicated and complicated CAP. No statistically significant differences were found between the groups regarding age at admission, gestational age, birth weight, gender, or socioeconomic variables. Significant differences were found between the groups regarding history of pneumonia (p = 0.03), previous antibiotic therapy (p = 0.004), time elapsed since the onset of CAP (p = 0.01), duration of fever prior to admission (p < 0.001), duration of antibiotic therapy (p < 0.001), and length of hospital stay (p < 0.001). In the multivariate analysis, only duration of fever prior to admission remained in the model (OR = 1.97; 95% CI: 1.36-2.84; p < 0.001). Conclusions: Biological variables, especially duration of fever prior to admission, appear to be associated with the development of complications in children with CAP.

Keywords: Community-acquired infections; Pneumonia; Pleural Effusion.

Objective: To analyze the shuttle walk test, and its respective retest, comparing children with cystic fibrosis (CF) to normal children. Methods: The children were divided into two groups: the CF group, composed of children in whom the diagnosis had been confirmed through sweat testing; and the control group, composed of normal children with no history of pulmonary diseases and no alterations in respiratory function. The children were submitted to at least two consecutive tests, 30 min apart. We evaluated distance walked, cardiac overload, peripheral oxygen saturation (SpO2) and subjective perception of exertion (dyspnea at rest scale and Borg dyspnea scale). Results: A total of 28 children were evaluated. Ages ranged from 7 to 15 years (11.57 ± 2.50 and 11.28 ± 1.85 years for the CF and control groups, respectively). The Borg scale scores were significantly higher in the controls (p = 0.007). No differences were found regarding cardiac overload and SpO2. In relation to the intergroup retest, the controls presented significant improvements on the second test, both in the distance walked and in dyspnea at rest (p = 0.014 and p = 0.036, respectively). The CF group presented a significant improvement only in the dyspnea at rest score (p = 0.168 and p = 0.042, respectively). Conclusion: The cardiac overload imposed by the test did not differ between the groups. The greater fatigue at the beginning of the second test suggests that the 30 min rest between the tests was insufficient.

Keywords: Cystic fibrosis; Exercise test; Heart rate.