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BACKGROUND: Respiratory syncytial virus (RSV) is associated with severe lower respiratory tract infection (LRTI), especially in preterm infants. Other viruses, co-detected with RSV, may play a role in the severity of respiratory outcomes. METHODS: This prospective epidemiologic study of severe LRTI incidence among children born ≤35 weeks gestational age at 3 sites in Brazil (2008-2010) followed a birth cohort for 1 year post-enrollment. Nasal washes from subjects with LRTI were tested for respiratory viruses using polymerase chain reaction. The primary outcome was the incidence of severe LRTI requiring hospitalization associated with RSV infection. Secondary outcomes included identification of viruses associated with LRTI, alone or coinfections, and risk factors associated with severe LRTI. RESULTS: Among 303 subjects, 176 (58.1%) experienced LRTI. Among these subjects, 162 had samples tested using polymerase chain reaction; 27.8% (45/162) experienced severe LRTI. More subjects with severe LRTI were infected with RSV (30/45, 66.7%) than with other viruses. RSV was present in 33.1% (143/432) of LRTI events tested, 57.3% (82/143) were coinfections. RSV was the virus most frequently associated with severe LRTIs (34/56 events, 60.7%); 50% (17/34 events) single and 50% coinfections. Significantly longer hospital stays were associated with LRTI events involving RSV coinfections compared with RSV single infections (P = 0.012). Infants with severe LRTIs had significantly lower mean RSV-IgG levels at study entry compared with those with nonsevere or no LRTIs (P < 0.05). CONCLUSIONS: This study confirms the association of RSV alone or as a coinfection with severe LRTI and reinforces the importance of providing adequate prophylaxis for susceptible infants.

Summary. The detection of early airway disease in infants with cystic fibrosis (CF) may lead to earlier intervention and an improved prognosis. We hypothesized that the ratio of maximal expiratory flows while breathing a mixture of helium and oxygen (heliox) and air, referred to as density dependence (DD), would identify early airway disease in infants with CF who have normal lung function. We also hypothesized that these infants with CF might be better differentiated from normal infants when the flows breathing heliox are compared instead of room air flows. We evaluated 10 infants with CF and 21 infants without CF and with normal lung function, defined as a forced vital capacity (FVC) and forced expiratory flows between 25–75% of expired volume (FEF25–75) of greater than 70% predicted (z-score > −2.0). Full forced expiratory maneuvers by the rapid thoracic compression technique were obtained while breathing room air and then heliox. Flow at 50% and 75% of expired volume (FEF50, FEF75), FEF25–75, and FVC were calculated from the flow volume curve with patients and control subjects breathing each gas mixture. The ratio of heliox to air flow at FEF50 and FEF75 was calculated (DD50, DD75), and the point where the two flow-volume curves crossed (Viso V′) was also measured. DD parameters did not distinguish the infants with CF from the infants without CF; length-adjusted FEF50 breathing air was significantly lower in the infants with CF compared to the infants without CF (P

Forced expiratory flows (FEF) can be measured in infants from lung volumes initiated near total lung capacity. In order to establish reference values and to evaluate lung growth, we obtained measurements in 155 healthy subjects between 3 and 149 wk of age. Forced vital capacity (FVC) was highly correlated with body length; however, after accounting for length, age was also significant. When subjects were divided at the median age (40 wk) younger compared with older subjects had a significantly larger slope for length (3.7 versus 2.8; p = 0.002). The flow parameters (FEF(50), FEF(75), FEF(85), and FEF(25-75)) were highly correlated with length, and those infants whose mothers smoked had lower flows. For FEF(75), male subjects had lower flows than female subjects. The relationship between FEF and volume was assessed using FEV(0.5)/FVC, which decreased with increasing length. Smaller subjects emptied their lung volume proportionately faster. We conclude that our study provides reference values for this age group and demonstrates that smoke-exposed infants and male subjects have decreased FEF. In addition, our findings indicate that lung volume increases most rapidly during the first year of life and that airways are large relative to lung volume very early in life.

Although pulmonary function testing plays a key role in the diagnosis and management of chronic pulmonary conditions in children under 6 years of age, objective physiologic assessment is limited in the clinical care of infants and children less than 6 years old, due to the challenges of measuring lung function in this age range. Ongoing research in lung function testing in infants, toddlers, and preschoolers has resulted in techniques that show promise as safe, feasible, and potentially clinically useful tests. Official American Thoracic Society workshops were convened in 2009 and 2010 to review six lung function tests based on a comprehensive review of the literature (infant raised-volume rapid thoracic compression and plethysmography, preschool spirometry, specific airway resistance, forced oscillation, the interrupter technique, and multiple-breath washout). In these proceedings, the current state of the art for each of these tests is reviewed as it applies to the clinical management of infants and children under 6 years of age with cystic fibrosis, bronchopulmonary dysplasia, and recurrent wheeze, using a standardized format that allows easy comparison between the measures. Although insufficient evidence exists to recommend incorporation of these tests into the routine diagnostic evaluation and clinical monitoring of infants and young children with cystic fibrosis, bronchopulmonary dysplasia, or recurrent wheeze, they may be valuable tools with which to address specific concerns, such as ongoing symptoms or monitoring response to treatment, and as outcome measures in clinical research studies.

Objective To explore the relationship between prematurity, gender and chorioamnionitis as determinants of early life lung function in premature infants. Methods Placenta and membranes were collected from preterm deliveries (

Summary Aim To generate reference values for respiratory muscle strength in healthy children aged three to twelve years. Methods Participants were recruited from three schools and selected after a respiratory disease questionnaire analysis and written informed consent by parents or guardians. All participants included in the study had normal spirometry, height and weight were measured on the same day. Respiratory muscle strength was evaluated by a single examiner following the guidelines for pulmonary function tests. The association between MIP and MEP values with the potential predictive variables was analyzed using a multiple linear regression model. Results A total of 171 participants were selected and distributed evenly by age. The age, height, weight and forced vital capacity showed moderate to strong correlations with both respiratory pressures. However, the regression model showed that height and weight were the best variables to predict MIP in both sexes, and age and weight to predict MEP. The power of prediction ( R 2 ) ranged from 46 to 58%. The intraclass correlation coefficient was used in a subgroup and demonstrated excellent reproducibility between tests. Conclusion The results of this study demonstrate that the behavior of respiratory muscle strength in healthy preschool and school children can be explained by age, height and weight.

Rationale: Given the role of vascular endothelial growth factor (VEGF) in lung development, we hypothesized that polymorphisms in VEGF-A may be associated with lung function. Objectives: The current study was designed to assess the role of genetic variants in VEGF-A as determinants of airway function from infancy through early adulthood. Methods: Association between five single-nucleotide polymorphisms (SNPs) in VEGF-A and lung function were assessed longitudinally in two unselected birth cohorts and cross-sectionally among infants. Replication with two SNPs was conducted in adults and children with asthma. We investigated the functionality of the SNP most consistently associated with lung function (rs3025028) using Western blotting to measure the ratio of plasma VEGF-A 165b/panVEGF-A 165among homozygotes. Measurements and Main Results: In two populations in infancy, C-allele homozygotes of rs3025028 had significantly higher VmaxFRC, forced expiratory flow 50, and forced expiratory flow 25-75 compared with other genotype groups. Among preschool children (age 3 yr), C allele of rs3025028 was associated with significantly higher specific airway conductance, with similar findings observed for lung function in school-age children. For FEV 1/FVC ratio similar findings were observed among adolescents and young adults (birth cohort), and then replicated in adults and school children with asthma (cross-sectional studies). For rs3025038, plasma VEGF-A 165b/panVEGF-A 165 was significantly higher among CC versus GG homozygotes (P ≤ 0.02) at birth, in school-age children, and in adults. Conclusions: We report significant associations between VEGF-A SNP rs3025028 and parameters of airway function measured throughout childhood, with the effect persisting into adulthood. We propose that the mechanism may be mediated through the ratios of active and inhibitory isoforms of VEGF-A 165, which may be determined by alternative splicing. Copyright © 2012 by the American Thoracic Society.

To test the hypothesis that azithromycin reduces the length of hospitalization and oxygen requirement in infants with acute viral bronchiolitis (AB).We performed a randomized, double-blinded, placebo-controlled trial in southern Brazil, from 2009 to 2011. Infants (12 months of age) hospitalized with AB were recruited in 2 hospitals. Patients were randomized to receive either azithromycin or placebo, administered orally, for 7 days. At enrollment, clinical data were recorded and nasopharyngeal samples were collected for viral identification through immunofluorescence. Main outcomes were duration of oxygen requirement and length of hospitalization.One hundred eighty-four patients were included in the study (azithromycin 88 subjects, placebo 96 subjects). Baseline clinical characteristics and viral identification were not different between the groups studied. A virus was detected in 112 (63%) patients, and of those, 92% were positive for respiratory syncytial virus. The use of azithromycin did not reduce the median number of days of either hospitalization (P = .28) or oxygen requirement (P = .47).Azithromycin did not improve major clinical outcomes in a large sample of hospitalized infants with AB, even when restricting the findings to those with positive respiratory syncytial virus samples. Azithromycin therapy should not be given for AB because it provides no benefit and overuse increases overall antibiotic resistance.

Asthma is the most common chronic pulmonary disease, characterized by bronchial inflammation. Some children with asthma have persistent pulmonary function impairment. The prevalence and etiology of this abnormality in children with asthma in developing countries remain unknown. The objective of this study was to estimate the proportion of patients with impaired pulmonary function who were unresponsive to treatment in a group of children and adolescents with asthma, and to describe the phenotypic characteristics of the sample.Using a standardized questionnaire, we selected outpatients (5-17 years of age) diagnosed with persistent asthma. These patients underwent spirometry and skin prick tests for sensitivity to common aeroallergens. Persistent pulmonary function impairment was defined as an FEV1/FVC ratio0.80, even after 10 days of treatment with bronchodilators and oral corticosteroids. We used the atopic index to differentiate between patients with little or no response to the skin prick test and those with a strong response (cut-off point: 4 allergens).We included 96 patients with a mean age of 10.6 years. Of those, 52 (54.1%) were male, and 89 (92.7%) were atopic. Of the 96 patients, 8 (8.3%) had impaired pulmonary function even after the treatment. Among those patients, 8 (100%) were atopic, 7 (87.5%) had moderate or severe asthma, and 7 (87.5%) had a history of hospitalization for acute bronchiolitis.Children and adolescents with moderate or severe asthma can present with impaired pulmonary function and be unresponsive to treatment. This clinical situation has been little studied in developing countries, and its risk factors and etiology will be better understood only through birth cohort studies.

To evaluate the acceptability and reproducibility of spirometry in preschool children; to estimate the effect size of early termination of exhalation (ETE) on FVC, FEV(1) and FEV(0.5); and to evaluate the validity of FEV(0.5) in curves with ETE.Spirometric data were obtained from 240 healthy preschool children, who were selected by simple sampling. On the basis of the best curve from each child according to the end of exhalation, three groups were formed: no ETE (nETE); ETE and flow ≤ 10% of the highest PEF (ETE≤10); and ETE and flow10% of the highest PEF value (ETE10). The reproducibility of FVC, FEV(1) and FEV(0.5) was compared among the three groups. The effect of ETE on FVC, FEV(1), and FEV(0.5) was assessed.Of the 240 children tested, 112 (46.5%)-82 (34.0%) of those in the nETE group and 30 (12.5%) of those in the ETE≤10 group--had acceptable curves for all the parameters. In 64 (27.0%) of those in the ETE10 group, the curves were acceptable only for FEV(0.5), increasing the proportion of children with valid FEV(0.5) to 73.0%. There were no significant differences between the nETE and ETE≤10 groups in terms of the mean values of the parameters assessed.Maneuvers with ETE and flow ≤ 10% of the highest PEF are valid. In individuals with a flow10% of the highest PEF value, these maneuvers are only valid for FEV(0.5).

Background Childhood asthma is most often characterized by recurrent wheezing, airway hyperreactivity, and atopy; however, our understanding of these relationships from early in life remains unclear. Respiratory tract illnesses and atopic sensitization early in life might produce an interaction between innate and acquired immune responses, leading to airway inflammation and heightened airway reactivity. Objective We hypothesized that premorbid airway reactivity and immunologic characteristics of infants without prior episodes of wheezing would be associated with subsequent wheezing during a 1-year follow-up. Methods One hundred sixteen infants with chronic dermatitis were enrolled before episodes of wheezing. Airway reactivity, allergen-specific IgE levels, cytokine production by stimulated PBMCs, and percentages of dendritic cells were measured on entry, and airway reactivity was reassessed at the 1-year follow-up. Linear regression models were used to evaluate a predictor's effect on continuous outcomes. Results Milk sensitization, egg sensitization, or both were associated with heightened airway reactivity before wheezing and after the onset of wheezing; however, these factors were not associated with an increased risk of wheezing. There was an interaction between initial airway reactivity and wheezing as a determinant of airway reactivity at follow-up. In addition, cytokine production by stimulated PBMCs was a risk factor for wheezing, whereas increased percentages of conventional dendritic cells were protective against wheezing. Conclusion Our data in a selected cohort of infants support a model with multiple risk factors for subsequent wheezing that are independent of initial airway reactivity; however, the causative factors that produce wheezing very early in life might contribute to heightened airway reactivity.

Obstructive lung diseases remain as important complications of preterm birth, usually attributed to a combination of lung immaturity, oxygen therapy and ventilator support. This is particularly true for low birth weight infants with severe respiratory neonatal disease; however, preterm infants that did not initially demonstrate significant respiratory neonatal disease also have reduced lung function when examined later in life, suggesting that prematurity alone could generate a persistent obstructive disease. Recent data have shown a significant reduction in maximal expiratory flows in healthy premature infants compared with control infants and reference values, when tested in the first months of life. Reduced expiratory flows were associated with male sex, low gestational age, smoking exposure and increased weight gain. The mechanism for this has not been determined and could result from smaller airways, a decrease in pulmonary elastic recoil secondary to abnormal alveolarisation of the lung parenchyma, as well as more compliant airways.

Background: Asthma phenotypes are well described among children. However, there are few studies comparing airway inflammation in different clinical presentations of pediatric asthma. We tested the hypothesis that nonatopic asthma is associated with a predominant noneosinophilic inflammation in the airways, as assessed by induced sputum. The objective of this study was to evaluate the cytological characteristics of induced sputum (IS) in atopic (AA), nonatopic asthmatics (NAA) and nonatopic nonasthmatic children (NANA). Methods: Of 90 selected children, 77 met eligibility criteria for performing IS and were classified as: AA, n = 28, NAA, n = 29 and NANA, n = 19. Subjects answered to a set of ISAAC-based questions and were skin-tested for common aeroallergens. A defined series of exclusion criteria was applied. Results: Induced sputum was obtained from 54 (70.1%) subjects (21 AA, 20 NAA and 13 NANA). Demographic data and mean FEV1 were similar in the three groups. The proportion of eosinophils [median, inter quartile range (IQR)] was significantly higher in the sputum of AA [(6.0.)12)] compared with NAAs [0 (2)] and NANAs [0 (1)], P 3%) was also significantly higher in AA (71.4%) when compared with NAA (28.6%); none of the NANA had sputum eosinophilia. Nonatopic asthmatic children had significantly higher proportions and absolute number of neutrophils than AA and controls. Conclusions: The results suggest that nonatopic children present IS with a cell pattern that is predominantly neutrophilic while eosinophilia is the hallmark of airway inflammation in the majority of atopic wheezing children not treated with inhaled steroids.

Rationale: Early in life, lung growth can occur by alveolarization, an increase in the number of alveoli, as well as expansion. We hypothesized that if lung growth early in life occurred primarily by alveolarization, then the ratio of pulmonary diffusion capacity of carbon monoxide (DlCO) to alveolar volume (VA) would remain constant; however, if lung growth occurred primarily by alveolar expansion, then DlCO/VA would decline with increasing age, as observed in older children and adolescents. Objectives: To evaluate the relationship between alveolar volume and pulmonary diffusion capacity early in life. Methods: In 50 sleeping infants and toddlers, with equal number of males and females between the ages of 3 and 23 months, we measured DlCO and VA using single breath-hold maneuvers at elevated lung volumes. Measurements and Main Results: DlCO and VA increased with increasing age and body length. Males had higher DlCO and VA when adjusted for age, but not when adjusted for length. DlCO increased with VA; there was no gender difference when DlCO was adjusted for VA. The ratio of DlCO/VA remained constant with age and body length. Conclusions: Our results suggest that surface area for diffusion increases proportionally with alveolar volume in the first 2 years of life. Larger DlCO and VA for males than females when adjusted for age, but not when adjusted for length, is primarily related to greater body length in boys. The constant ratio for DlCO/VA in infants and toddlers is consistent with lung growth in this age occurring primarily by the addition of alveoli rather than the expansion of alveoli.

Background and objective: Pulmonary aspiration (PA) is a significant respiratory disease in children. However, the diagnosis of aspiration is often difficult owing to the poor efficacy of currently available diagnostic tests. The aim of this study was to assess in a mouse model the specificity of starch granule detection in BAL as a new method for detecting PA in children. Methods: Twenty BALB/c mice were divided into the following groups according to the solution instilled into the airways: corn flour milk 7.5%—a source of starch (CM), Pseudomonas aeruginosa, normal saline and a control group. BAL was performed 2 days after instillation. Detection of starch granules and lipid-laden macrophages were compared in BAL. Results: Starch granules were detected in BAL fluids from all mice in the CM group (food aspiration model), whereas no starch granules were detected in the other three groups, demonstrating a sensitivity and specificity of 100%. On the other hand, lipid-laden macrophages were found in all mice from all the groups studied. Conclusions: The detection of starch granules in BAL is a simple and highly specific method for the diagnosis of PA in an experimental model. Clinical studies using the starch granule detection method in BAL should be tested in at risk patients to evaluate the utility of this method for investigating PA.

OBJETIVO: Verificar a prevalência de sintomas de distúrbios respiratórios do sono em crianças de baixo nível socioeconômico no Sul do Brasil. MÉTODOS: Foi realizado um estudo transversal em Uruguaiana (RS), utilizando questionário específico sobre sintomas de distúrbios respiratórios do sono, respondido pelos pais, em uma amostra de escolares de 9 a 14 anos participantes do International Study of Asthma and Allergies in Childhood (ISAAC). RESULTADOS: Foram respondidos 998 questionários de um total de 1.011 escolares elegíveis. Relato de ronco habitual ocorreu em 27,6% das crianças, apnéia em 0,8%, respiração oral diurna em 15,5% e sonolência diurna excessiva em 7,8%. Crianças com sonolência diurna excessiva apresentaram maior risco de ronco habitual (OR = 2,7; IC95% 1,4-5,4), apnéia (OR = 9,9; IC95% 1,2-51), respiração oral (OR = 13,1; IC95% 6,2-27,4) e problemas de aprendizado (OR = 9,9; IC95% 1,9-51,0). Rinite, fumo materno e testes cutâneos alérgicos estiveram significativamente associados a ronco habitual e respiração oral diurna. CONCLUSÕES: A prevalência de sintomas de distúrbios respiratórios do sono é elevada em crianças de 9 a 14 anos na cidade de Uruguaiana. A prevalência de ronco habitual foi quase duas vezes maior que a descrita nessa faixa etária em outras populações. Crianças com sonolência diurna excessiva parecem ter quase 10 vezes mais risco de problemas de aprendizado. OBJECTIVE: To identify the prevalence of symptoms of sleep-disordered breathing among children of low socioeconomic status in the South of Brazil. METHODS: This was a cross-sectional study, carried out in the city of Uruguaiana, RS, in which specific questionnaire about the symptoms of sleep-disordered breathing was completed by the parents of a sample of schoolchildren aged 9 to 14 years, enrolled on the International Study of Asthma and Allergies in Childhood (ISAAC). RESULTS: From the total of 1,011 eligible schoolchildren, 998 questionnaires were completed. The parents of 27.6% of the children reported habitual snoring, while 0.8% reported apnea, 15.5% described daytime mouth breathing and 7.8% complained of excessive daytime sleepiness. Children with excessive daytime sleepiness were at greater risk of habitual snoring (OR = 2.7; 95%CI 1.4-5.4), apnea (OR = 9.9; 95%CI 1.2-51), mouth breathing (OR = 13.1; 95%CI 6.2-27.4) and learning difficulties (OR = 9.9; 95%CI 1.9-51.0). Rhinitis, maternal smoking and positive allergy skin test results were significantly associated with habitual snoring and daytime mouth breathing. CONCLUSIONS: There is an elevated prevalence of symptoms of sleep-disordered breathing among children from 9 to 14 in the city of Uruguaiana. The prevalence of habitual snoring was almost twice that described in this age group in other populations. Children with excessive daytime sleepiness appear to have almost 10 times the risk of learning difficulties.

The interrupter technique is used for determining interrupter resistance (Rint) during quiet breathing. This noninvasive method requires minimal cooperation and can therefore be useful in evaluating airway obstruction in uncooperative children. To date, no reference values have been determined for Rint in a Brazilian population. The objective of this study was to define a prediction equation for airway resistance using the interrupter technique for healthy children aged 3-13 years.This was a prospective, cross-sectional study involving preschool and school children in Porto Alegre, Brazil, in whom Rint was measured during peak expiratory flow.One-hundred and ninety-three children were evaluated. Univariate analysis using linear regression showed that height, weight and age correlated significantly and independently with Rint. Multiple regression with height, weight, age and gender as variables resulted in a model in which only height and weight were significant, independent predictors of Rint. Collinearity was identified among height, weight and age.Reference values and an equation for calculating Rint in healthy children were obtained and are adjusted for height.

The role of airway inflammation in ventilated preterm newborns and the risk factors associated with the development of chronic lung disease are not well understood. Our objective was to analyze the association of the airway inflammatory response in ventilated preterm infants by serial measurements of TNF-a and IL-10 in tracheobronchial lavage (TBL) with perinatal factors and lung function measured early in life. A series of TBL samples were collected from ventilated preterm infants (less than 32 weeks of gestational age) and concentrations of TNF-a and IL-10 were measured by ELISA. Pulmonary function tests were performed after discharge by the raised volume rapid compression technique. Twenty-five subjects were recruited and 70 TBL samples were obtained. There was a significant positive association between TNF-a and IL-10 levels and length of time between the rupture of the amniotic membranes and delivery (r = 0.65, P = 0.002, and r = 0.57, P < 0.001, respectively). Lung function was measured between 1 and 22 weeks of corrected age in 10 patients. Multivariable analysis with adjustment for differences in lung volume showed a significant negative association between TNF-a levels and forced expiratory flow (FEF50; r = -0.6; P = 0.04), FEF75 (r = -0.76; P = 0.02), FEF85 (r = -0.75; P = 0.03), FEF25-75 (-0.71; P = 0.02), and FEV0.5 (r = -0.39; P = 0.03). These data suggest that TNF-a levels in the airways during the first days of life were associated with subsequent lung function abnormalities measured weeks or months later.

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The present study is aimed to describe the changes in the prevalence of symptoms of asthma, rhinitis and eczema among Brazilian adolescents (AD, 13-14 years old) between Phases 1 and 3 of the International Study of Asthma and Allergies in Childhood (ISAAC). The prevalence of self-reported symptoms of asthma, rhinitis and eczema in AD from five Brazilian cities (Curitiba, Porto Alegre, Recife, Salvador and São Paulo), obtained during ISAAC Phase 1 (n = 15 419) and Phase 3 (n = 15 684), was compared to determine the trend of prevalence in a 7-year interval. There was a trend to reduction in the current prevalence of wheezing and increasing of nocturnal cough when averaging figures from the five cities. The prevalence of wheezing in the last 12 months was 27.7 vs. 19.9% (p0.01); asthma ever 14.9 vs. 14.7% (p0.05); severe episode of wheezing 5.2 vs. 5.2%; nocturnal cough 32.6 vs. 34.9% (p0.01); exercise wheezing 23.6 vs. 23.0% (p0.05) and awake with wheezing 11.8 vs. 11.2% (p0.05). Similar things were observed with the prevalence of current symptoms of rhinitis and eczema. In Brazil, there was a small but significant mean decrease in the prevalence of two asthma-related symptoms, wheezing and nocturnal cough, though this trend was not consistent in the surveyed cities. The prevalence of asthma symptoms in Brazil, despite its mean trend to a decrease, is still one of the highest in Latin America.

Objective: Plastic bronchitis is an unusual condition in children, associated with formation of mucofibrinous casts and mucous plugging of the tracheobronchial tree. Given that this illness is part of the differential diagnosis of acute respiratory failure, early treatment is important for improved prognosis. The aim of this report is to describe a case of plastic bronchitis in a child with alpha-thalassemia that was treated successfully with endoscopy. Description: A 3 year old, black, male child, previously healthy, presented with acute respiratory failure and a chest x-ray showing pulmonary atelectasis. There was no evidence of respiratory symptoms or previous allergy state. The diagnosis of plastic bronchitis was made using flexible and rigid bronchoscopy, and confirmed by histopathologic findings. The child progressed well, treatment was based on supportive care and antibiotics were not used. Ten days after discharge, radiographic appearance was normal. Alpha thalassemia was diagnosed through hemoglobin electrophoresis. Comments: Plastic bronchitis is clinically important because has similar presentation to other prevalent diseases, such as foreign body aspiration and asthma. When plastic bronchitis is suspected, endoscopy is indicated in order to confirm diagnosis and define treatment. Plastic bronchitis has been previously described in patients with cystic fibrosis, cardiac surgery and sickle cell disease. In this case, an association with alpha-thalassemia was observed.

Epidemiological and experimental studies have demonstrated an association between parasitic infections and the allergic diseases. A protective effect in asthma was shown in animals infected with helminths. The aim of this study was to determine the effect of Angiostrongylus costaricensis extract on inflammatory lung response to ovalbumin (OVA) in mice. Four BALB/c mice received A. costaricensis extract by intraperitoneal (i.p.) injection on the first day. Mice were immunised against OVA by i.p. injection on day (D) 5 and D12 and received a daily intranasal OVA challenge (40 microl) between the D19 and D21. On D23, we performed a bronchoalveolar lavage (BAL) on the mice. Four BALB/c mice (control group) were immunised against OVA using the same protocol, but did not receive parasite extract. Total cell counts (TCC) and differential cell counts were performed in BAL fluid samples. Eosinophil cell counts in BAL fluid were lower in the group that received A. costaricensis extract when compared with the control group (0.04 x 10(6) cells/ml and 0.01 x 10(6) cells/ml, respectively; p=0.04). TCC were not different between the groups studied. A. costaricensis extract in mice decreases eosinophilic response to OVA in BAL fluid.

OBJETIVO: O aumento da sobrevida de prematuros traz o desafio de lidar com um amplo espectro de doenças pulmonares crônicas, incluindo displasia broncopulmonar, síndrome de Wilson-Mikity e sibilância recorrente. Este artigo discute o prognóstico pulmonar clínico e funcional de prematuros na infância e na adolescência. FONTE DE DADOS: Foi realizada pesquisa no MEDLINE de publicações entre 1970 e 2004 que abordassem função e crescimento pulmonar de prematuros, bem como a evolução clínica dos mesmos. SÍNTESE DOS DADOS: Eventos pré e pós-natais como insuficiência placentária, tabagismo, infecções, oxigênio e ventilação mecânica exercem efeitos importantes no desenvolvimento pulmonar, podendo conduzir a doenças pulmonares crônicas, sendo a displasia broncopulmonar a complicação clínica mais severa. No entanto, perdas significativas de função pulmonar também podem ocorrer em prematuros sem critérios de displasia broncopulmonar e que não apresentaram doença respiratória neonatal significativa. Nestes pacientes, o impacto da prematuridade sobre o sistema respiratório é freqüentemente subestimado. Clinicamente, observa-se incidência aumentada de pneumonias e bronquiolites, re-hospitalizações por doenças respiratórias, tosse e sibilância crônicas e hiper-reatividade brônquica. Posteriormente, percebe-se uma tendência à normalização da função pulmonar, mas persistem fluxos reduzidos, menor tolerância a exercícios e hiper-reatividade brônquica. CONCLUSÕES: A prematuridade, os eventos que a provocam e as intervenções que dela decorrem alteram de maneira permanente, em maior ou menor grau, o desenvolvimento do sistema respiratório. São necessários estudos adicionais para esclarecer o efeito de cada um desses insultos perinatais no desenvolvimento do sistema respiratório. OBJECTIVE: The increased survival of preterm infants poses the challenge of dealing with a wide range of chronic pulmonary diseases, including bronchopulmonary dysplasia, Wilson-Mikity syndrome and recurrent wheezing. This article reviews the pulmonary clinical and functional prognosis of preterm newborns in infancy and adolescence. SOURCE OF DATA: MEDLINE search for articles published between 1970 and 2004 that focused on lung growth and function of preterm infants, besides a clinical follow-up of this group. SUMMARY OF THE FINDINGS: Prenatal and postnatal events, such as placental insufficiency, tobacco exposure, infections, oxygen and mechanical ventilation, have an important effect on lung development and can lead to chronic lung diseases, of which bronchopulmonary dysplasia is the most severe complication. However, significant loss of lung function occurs in preterm infants who do not fulfill the criteria for bronchopulmonary dysplasia, and even in those who did not have significant respiratory disease during the neonatal period. The impact of prematurity on the respiratory system of these patients is usually underestimated. Clinically, preterm infants have an increased incidence of pneumonia and bronchiolitis, hospital readmissions due to respiratory diseases, chronic cough and wheezing and bronchial hyperresponsiveness. In adolescence, there is a tendency for normalization of the lung function, but they persist with reduced flows, lower exercise tolerance and bronchial hyperresponsiveness. CONCLUSION: Prematurity, the events that cause it and the interventions that follow it permanently change the development of the respiratory system. Studies are necessary to clarify the effect of each of these perinatal insults on the development of the respiratory system.

Wheezing associated with respiratory viral infections in infancy is very common and results in high morbidity worldwide. The Th1/Th2 pattern of immune response in these patients remains unclear and previous studies have shown controversial results. The aim of the present study was to compare the type of Th1/Th2 cytokine response between infants with acute bronchiolitis, recurrent wheezing and upper respiratory infections from a developing country. Infants younger than 2 years of age admitted to Hospital São Lucas, Porto Alegre, RS, Brazil, between May and November 2001, with an acute episode of wheezing associated with viral respiratory infection were selected. Subjects with upper respiratory infections from the emergency department were selected for the control group. Interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) levels from nasal aspirates were determined by ELISA from peripheral mononuclear cell cultures. Twenty-nine subjects with acute bronchiolitis, 18 with recurrent wheezing and 15 with upper respiratory infections were enrolled. There were no differences in family history of atopy or parental smoking between groups. Oxygen requirement was similar for the acute bronchiolitis and recurrent wheezing groups. The percentage of positive tests for the cytokines studied and the IFN-gamma/IL-4 ratio was similar for all groups. Comparison of the polarized Th1/Th2 cytokine results for the various groups showed no specific pattern of cytokine production. Infants with wheezing from a developing country do not show any specific predominant pattern of Th1/Th2 cytokine production, suggesting that multiple factors may be involved in the pathogenesis of this illness.

Background Many studies have measured cytokine production derived from peripheral blood mononuclear cells (PBMCs) to evaluate the immune response in acute bronchiolitis (AB), but no previous reports have examined the association between PBMC release of cytokines and concomitant airway immune response. Objective To determine whether interferon-γ (IFN-γ), interleukin 4 (IL-4), and IL-10 levels from PBMCs are associated with concurrent cytokine release in the airways of infants with AB. Methods Infants with acute viral-associated first episode of wheezing who required hospitalization between May and September 2002 were recruited. Nasopharyngeal aspirates (NPAs) and PBMC samples were collected simultaneously. The concentrations of IFN-γ, IL-4, and IL-10 in NPA and PBMC supernatants were determined by enzyme-linked immunosorbent assay. Results Twenty infants with AB were enrolled in the study of whom 17 (85%) had positive NPA immunofluorescence results for viral detection and respiratory syncytial virus. Median total cell count and viability from NPA samples were 2.2 × 10 6 cells/mL (SD, 1.7 cells/mL) and 92% (SD, 6.0%), respectively. There was a significant correlation between IL-4 levels from NPA and PBMC samples ( r = 0.5, P = .02); however, we did not find an association between IFN-γ and IL-10 levels. Conclusions Cytokines produced by in vitro PBMCs may not necessarily reflect the concurrent cytokine pattern production at the mucosal surface in the respiratory tract of infants with AB. Further studies are required to determine whether peripheral blood is a reliable sample for airway inflammation evaluation and to explain the discrepancies of cytokine productions found in this study.

Over the last two decades since its emergence human immunodeficiency virus (HIV) infection has been a major epidemiological problem. There are 42 million people living with HIV/AIDS worldwide and 3.2 million are children under the age of 15. The epidemic continues to expand rapidly in many countries. Most of the HIV/AIDS patients are from developing countries and Africa has the highest prevalence of this illness in the world. Mother-to-child transmission is estimated to happen in 85% of children with HIV infection. Pulmonary involvement is common and responsible for almost 80% of the symptoms in children under 12 months of age. Bacterial pneumonia~ can be recurrent in AIDS patients and are the main cause of hospital admissions. The same bacteria associated to pneumonia in immune competent children are also observed in AIDS patients. HIV positive children are at higher risk for pneumonia associated to opportunistic agents like protozoa viruses fungi and mycobacteria. Most children with AIDS develop some type of lung disease throughout life. Pneumocystis carinii pneumonia (PCP) and lymphocytic interstitial pneumonitis (LIP) used to be even more prevalent until very recently. With earlier diagnosis and new treatments the prevalence of these illnesses has been changing over the last years. Since the mid- to late 1990s a dramatic decrease in the frequency of most opportunistic infections and other severe manifestations of HIV infection in children has been observed in pediatric AIDS due primarily to the development and implementation of guidelines for PCP prophylaxis and availability of highly active antiretroviral therapy. (excerpt)

Objective The objective of the present article is to present a review of the main clinical issues faced by pediatricians while defining the diagnosis, management and prognosis of postinfectious bronchiolitis obliterans. Sources Data from national and international scientific journals selected from the Lilacs and Medline databases. Summary of the findings With the purpose of establishing the diagnosis, a radiological investigation shows high levels of pulmonary insufflation, thickened bronchovascular bundles and, less often, bronchiectasis, atelectasis and pulmonary hyperlucency. The CT exam allows the visualization of structural and functional findings, such as air trapping, bronchiectasis and mosaic pattern. Lung function tests in children and infants always reveal significant reduction of expiratory flows. Pulmonary biopsy is not mandatory in order to confirm bronchiolitis obliterans. Diagnosis can be established through the combination of history of bronchiolitis, chronic obstructive pulmonary disease and typical tomographic findings. The treatment used by most services includes oral and inhaled corticosteroids and bronchodilators for long periods. The management of exacerbated conditions often requires antibiotics and physical therapy. Conclusions Most patients present a favorable outcome with slow improvement of the pulmonary function and reduced necessity for supplementary oxygen. Some patients present progressive worsening of hypoxemia and CO2 retention, which leads to pulmonary hypertension and cor pulmonale. Postinfectious bronchiolitis obliterans is mild and moderate in most patients, with consequent good prognosis and low mortality.

We evaluated the ability of forced expiratory flow volume curves from raised lung volumes to assess airway function among infants with differing severities of respiratory symptoms. Group 1 (n = 33) had previous respiratory symptoms but were currently asymptomatic; group 2 (n = 36) was symptomatic at the time of evaluation. As a control group, we used our previously published sample of 155 healthy infants. Flow volume curves were quantified by FVC, FEF50, FEF75, FEF25-75, FEV0.5, and FEV0.5/FVC, which were expressed as Z scores. All variables except FVC had Z scores that were significantly less than zero and distinguished groups 1 and 2 with progressively lower Z scores. The mean Z scores of the flow variables (FEF50%, FEF75%, and FEF25-75%) were more negative than the Z scores for the timed expired volumes (FEV0.5 or FEV0.5/FVC) for both groups. In general, measures of flow identified a greater number of infants with abnormal lung function than measures of timed volume; FEF50 had the highest performance in detecting abnormal lung function. In summary, forced expiratory maneuvers obtained by the raised volume rapid compression technique can discriminate among groups of infants with differing severity of respiratory symptoms, and measures of forced expiratory flows were better than timed expiratory volume in detecting abnormal airway function.

Objetivos: o objetivo do presente texto é apresentar uma revisão acerca das principais questões clínicas que envolvem o pediatra frente ao diagnóstico, manejo e prognóstico da situação. Fontes de dados: foram utilizadas informações de artigos publicados em revistas científicas nacionais e internacionais, selecionadas das bases de dados Lilacs e Medline. Síntese dos dados: para fins diagnósticos, a investigação radiológica evidencia hiperinsuflação pulmonar, espessamento dos feixes broncovasculares e, menos freqüentemente, bronquiectasias, atelectasias e hiperlucência pulmonar. A tomografia computadorizada permite visualizar alterações estruturais e funcionais, como aprisionamento de ar, bronquiectasias e padrão mosaico. Estudos funcionais pulmonares, em crianças e lactentes, revelam invariavelmente redução acentuada dos fluxos expiratórios. Biópsia pulmonar não é obrigatória para confirmação de bronquiolite obliterante (BO). O diagnóstico pode ser feito pela combinação de história de bronquiolite, doença pulmonar obstrutiva crônica e alterações tomográficas características. O tratamento feito pela maioria dos centros inclui corticóides orais e inalatórios e broncodilatadores por períodos prolongados, e o manejo das exacerbações freqüentemente requer antibióticos e fisioterapia. Conclusões: a maioria dos pacientes tem uma evolução favorável, com lenta melhora da função pulmonar e da necessidade de oxigênio suplementar. Alguns pacientes evoluem com piora progressiva da hipoxemia e retenção de CO2, levando à hipertensão pulmonar e cor pulmonale. A maioria dos pacientes portadores de BO pós-infecciosa apresenta quadros leves e moderados, fazendo com que o prognóstico, em geral, seja bom, com baixa mortalidade. Objective: the objective of the present article is to present a review of the main clinical issues faced by pediatricians while defining the diagnosis, management and prognosis of postinfectious bronchiolitis obliterans. Sources: data from national and international scientific journals selected from the Lilacs and Medline databases. Summary of the findings: with the purpose of establishing the diagnosis, a radiological investigation shows high levels of pulmonary insufflation, thickened bronchovascular bundles and, less often, bronchiectasis, atelectasis and pulmonary hyperlucency. The CT exam allows the visualization of structural and functional findings, such as air trapping, bronchiectasis and mosaic pattern. Lung function tests in children and infants always reveal significant reduction of expiratory flows. Pulmonary biopsy is not mandatory in order to confirm bronchiolitis obliterans. Diagnosis can be established through the combination of history of bronchiolitis, chronic obstructive pulmonary disease and typical tomographic findings. The treatment used by most services includes oral and inhaled corticosteroids and bronchodilators for long periods. The management of exacerbated conditions often requires antibiotics and physical therapy. Conclusions: most patients present a favorable outcome with slow improvement of the pulmonary function and reduced necessity for supplementary oxygen. Some patients present progressive worsening of hypoxemia and CO2 retention, which leads to pulmonary hypertension and cor pulmonale. Postinfectious bronchiolitis obliterans is mild and moderate in most patients, with consequent good prognosis and low mortality.

Forced expiratory flows by the rapid compression technique are often used to assess airway function in infants; however, it remains unclear as to whether flow limitation (FL) is achieved. Studies in adults have used negative expiratory pressure (NEP) at the airway opening as a noninvasive technique to assess whether FL is achieved. An increase in flow with NEP indicates that FL has not been achieved, whereas no increase in flow with NEP indicates FL has been achieved. In the adult studies, the change in flow was assessed by visual inspection of the flow-volume curve. We evaluated whether NEP could be used to assess FL during forced expiration in infants. In addition, we quantified the change in flow secondary to NEP. We applied -5 cm H(2)O NEP to four infants during forced expiratory maneuvers. The step increase in flow with NEP was always less than 5% at high jacket compression pressures and consistent with FL. For one subject, FL was also confirmed from isovolume pressure flow-curves measured with an esophageal catheter. We conclude that NEP can be used in infants to assess FL during forced expiratory maneuvers by the rapid compression technique.

Continuous positive airway pressure (CPAP) is used to minimize airway collapse in infants with tracheomalacia. Forced expiratory flows (FEFs) at functional residual capacity (FRC) increase with increasing CPAP in infants with tracheomalacia, and it has been suggested that CPAP prevents airway collapse by "stenting" the airway open. Since FEF is greater at higher than at lower lung volumes, we evaluated whether the increase in flow measured at FRC (V FRC) with CPAP could be explained by the increase in FRC with CPAP. We measured full FEF-volume curves at CPAP levels of 0, 4, and 8 cm H2O in six infants with tracheomalacia and five healthy control infants. In both groups of infants, FVC did not change with CPAP; however, inspiratory capacity (IC) decreased and thus FRC increased with increasing CPAP. FEFs at FRC increased with increasing levels of CPAP; however, the FEFs at 50% and 75% of expired volume were not different for the three levels of CPAP for both groups of infants. Our finding that FEFs measured at the same lung volumes did not differ for the different levels of CPAP indicates that CPAP affects forced flows primarily by increasing lung volume.

Objective: The pandemic caused by influenza A(H1N1)pdm09 virus peaked between July and August of 2009 in southern Brazil, with the highest incidence in children and young adults. In the post-pandemic period, there was an increase in the incidence of cases during the winter months of 2011 and 2012 in Brazil, similar to seasonal influenza virus. Since infections due to pandemic influenza are still occurring, the present study aimed to investigate the risk factors for worse outcome in children. Methods: A retrospective cohort study was performed by reviewing the charts of hospitalized patients younger than 14 years with reverse transcription-polymerase chain reaction (RT-PCR) positive for influenza A(H1N1)pdm09 during the first pandemic wave in six Brazilian tertiary centers. Need for mechanical ventilation was defined as the severity of outcome; age, chronic diseases, bacterial and viral co-detection, chest radiograph findings, and use of oseltamivir were possible predictors. Results: In the present study, 120 patients were included. In a multivariate analysis, chronic diseases (prevalence ratio: 2.613, 95% CI: 1.267-5.386) and viral co-detection (prevalence ratio: 2.43, 95% CI: 1.203-4.905) were statistically associated with worse outcome (p

ObjectiveTo generate prediction equations for spirometry in 4‐ to 6‐year‐old children.MethodsForced vital capacity, forced expiratory volume in 0.5s, forced expiratory volume in one second, peak expiratory flow, and forced expiratory flow at 25–75% of the forced vital capacity were assessed in 195 healthy children residing in the town of Sete Lagoas, state of Minas Gerais, Southeastern Brazil. The least mean squares method was used to derive the prediction equations. The level of significance was established as p

Objective: To present official longitudinal data on the impact of asthma in Brazil between 2008 and 2013. Methods: This was a descriptive study of data collected between 2008 and 2013 from an official Brazilian national database, including data on asthma-related number of hospitalizations, mortality, and hospitalization costs. A geographical subanalysis was also performed. Results: In 2013, 2,047 people died from asthma in Brazil (5 deaths/day), with more than 120,000 asthma-related hospitalizations. During the whole study period, the absolute number of asthma-related deaths and of hospitalizations decreased by 10% and 36%, respectively. However, the in-hospital mortality rate increased by approximately 25% in that period. The geographic subanalysis showed that the northern/northeastern and southeastern regions had the highest asthma-related hospitalization and in-hospital mortality rates, respectively. An analysis of the states representative of the regions of Brazil revealed discrepancies between the numbers of asthma-related hospitalizations and asthma-related in-hospital mortality rates. During the study period, the cost of asthma-related hospitalizations to the public health care system was US$ 170 million. Conclusions: Although the numbers of asthma-related deaths and hospital admissions in Brazil have been decreasing since 2009, the absolute numbers are still high, resulting in elevated direct and indirect costs for the society. This shows the relevance of the burden of asthma in middle-income countries. RESUMO Objetivo: Apresentar dados longitudinais oficiais sobre o impacto da asma no Brasil entre 2008 e 2013. Métodos: Estudo descritivo de dados extraídos de um banco de dados do governo brasileiro entre 2008 e 2013, no qual foram analisados as hospitalizações e óbitos por asma, bem como o custo das hospitalizações. Foi também realizada uma subanálise geográfica. Resultados: Em 2013, 2.047 pessoas morreram de asma no Brasil (5 óbitos/dia), com mais de 120.000 hospitalizações por asma. Durante o período de estudo, o número absoluto de óbitos e hospitalizações por asma diminuiu 10% e 36%, respectivamente. No entanto, a taxa de mortalidade hospitalar aumentou aproximadamente 25%. A subanálise geográfica mostrou que as regiões Norte/Nordeste e Sudeste apresentaram as maiores taxas de hospitalização e mortalidade hospitalar por asma, respectivamente. A análise dos estados representativos de cada região mostrou discrepâncias entre as hospitalizações por asma e as taxas de mortalidade hospitalar por asma. Durante o período de estudo, as hospitalizações por asma custaram US$ 170 milhões ao sistema público de saúde. Conclusões: Embora os óbitos e hospitalizações por asma no Brasil estejam diminuindo desde 2009, os números absolutos ainda são altos, com elevados custos diretos e indiretos para a sociedade, o que mostra a relevância do impacto da asma em países de renda média.

Airway caliber and lung volume (VL) increase many fold between infancy and adulthood; however, these two components of the lung may not increase proportionately during lung growth and development. We evaluated in infants the rate of emptying during forced expiration from near total lung capacity to residual volume. From the flow-volume curves we calculated (1) a rate constant (k) as the change in flow divided by the change in volume between 50% and 75% of expired forced vital capacity (FVC), and (2) the fraction of the FVC expired in 0.5 s (FEV(0.5)/FVC). Seventeen normal healthy infants were evaluated twice; mean ages (ranges) at first and second tests were 30 (5 to 76) and 58 (28 to 98) wk. Analysis of cross-sectional and longitudinal data indicated that the rate of emptying during forced expiration measured by both parameters was greatest in the youngest infants and decreased during infancy. Our findings are consistent with the concept that younger infants have large airways relative to their VL and that VL increases more rapidly than airway caliber early in life.

In older children and adults, density dependence (DD) of forced expiratory flow is present over the majority of the full flow-volume curve. In healthy subjects, DD occurs because the pressure drop from peripheral to central airways is primarily dependent on turbulence and convective acceleration rather than laminar resistance; however, an increase in peripheral resistance reduces DD. We measured DD of forced expiratory flow in 22 healthy infants to evaluate whether infants have low DD. Full forced expiratory maneuvers were obtained while the subjects breathed room air and then a mixture of 80% helium-20% oxygen. Flows at 50 and 75% of expired forced vital capacity (FVC) were measured, and the ratio of helium-oxygen to air flow was calculated (DD at 50 and 75% FVC). The mean (range) of DD at 50 and 75% FVC was 1.37 (1.22–1.54) and 1.23 (1.02–1.65), respectively, values similar to those reported in older children and adults. There were no significant relationships between DD and age. Our results suggest that infants, compared with older children and adults, have similar DD, a finding that suggests that infants do not have a greater ratio of peripheral-to-central airway resistance.

Background Lower respiratory tract infection (LRTI) is a major cause of pediatric morbidity and mortality, especially among non-affluent communities. In this study we determine the impact of respiratory viruses and how viral co-detections/infections can affect clinical LRTI severity in children in a hospital setting. Methods Patients younger than 3 years of age admitted to a tertiary hospital in Brazil during the months of high prevalence of respiratory viruses had samples collected from nasopharyngeal aspiration. These samples were tested for 13 different respiratory viruses through real-time PCR (rt-PCR). Patients were followed during hospitalization, and clinical data and population characteristics were collected during that period and at discharge to evaluate severity markers, especially length of hospital stay and oxygen use. Univariate regression analyses identified potential risk factors and multivariate logistic regressions were used to determine the impact of specific viral detections as well as viral co-detections in relation to clinical outcomes. Results We analyzed 260 episodes of LRTI with a viral detection rate of 85% (n = 222). Co-detection was observed in 65% of all virus-positive episodes. The most prevalent virus was Respiratory Syncytial Virus (RSV) (54%), followed by Human Metapneumovirus (hMPV) (32%) and Human Rhinovirus (HRV) (21%). In the multivariate models, infants with co-detection of HRV + RSV stayed 4.5 extra days (p = 0.004), when compared to infants without the co-detection. The same trends were observed for the outcome of days of supplemental oxygen use. Conclusions Although RSV remains as the main cause of LRTI in infants our study indicates an increase in the length of hospital stay and oxygen use in infants with HRV detected by RT-PCR compared to those without HRV. Moreover, one can speculate that when HRV is detected simultaneously with RSV there is an additive effect that may be reflected in more severe clinical outcome. Also, our study identified a significant number of children infected by recently identified viruses, such as hMPV and Human Bocavirus (HBov), and this is a novel finding for poor communities from developing countries.

The application of negative expiratory pressure (NEP) to the airway opening during forced expiratory maneuvers has recently been described as a noninvasive method to assess whether flow limitation is achieved in adults. This methodology has great potential for extending the measurement of forced expiratory maneuvers to young children who may not produce maximal efforts as reproducibly as adults. We used NEP to assess flow limitation in 10 children between 3 and 5 yr of age. NEP was well tolerated by all subjects. With the application of NEP, there was not a step increase in flow, a finding consistent with flow limitation for the subjects. In addition to visual inspection, we proposed a method to quantify the change in flow during a short NEP. The flow-volume curves obtained with and without NEP were visually the same, other than the flow transients produced by NEP. The calculated values of FVC and FEF25-75 were not significantly different when measured from flow- volume curves with and without NEP. There was a statistically significant increase in FEV1 with NEP; however, the group mean increase in FEV1 was less than 2%. We conclude that NEP may be a useful technique to determine whether flow limitation has been achieved in young children performing forced expiratory maneuvers.