Various wheezing phenotypes can be identified based on differences in natural histories, risk factors and responses to treatment. In epidemiologic studies, atopic asthma or virus-induced wheezing can be discriminated by the presence or the absence of sensitization to allergens. Children with asthma have been shown to present lower levels of lung function. Patients with viral respiratory infections evolve from normal lung function to enhanced airway reactivity. The objective of this study was to identify genes and polymorphisms associated with different wheezing phenotypes. Using data obtained from the Genetic Association Database, we systematically reviewed studies on genes and polymorphisms that have been associated with virus-induced wheezing or atopic asthma. The research was carried out in February of 2009. Genes associated with the studied outcomes in more than three studies were included in the analysis. We found that different genes and loci have been associated with virus-induced wheezing or atopic asthma. Virus-induced wheezing has frequently been associated with IL-8 polymorphisms, whereas atopic asthma and atopy have frequently been associated with Th2 cytokine gene (CD14 and IL-13) polymorphisms on chromosome 5. This review provides evidence that different wheezing disorders in childhood can be differently affected by genetic variations, considering their role on airway inflammation and atopy. Future studies of genetic associations should consider the different wheezing phenotypes in infancy. In addition, stratified analyses for atopy can be useful for elucidating the mechanisms of the disease.

Keywords: Genetics; Polymorphism, genetic; Asthma; Interleukins; Respiratory syncytial viruses.

Background: The decision to drain parapneumonic pleural effusion in children is still controversial. An indicative scoring system to assess the need for chest-tube drainage arose from a partnership between pediatricians and surgeons. Objective: To evaluate the utility of the score in indicating whether drainage should be performed in pediatric patients with parapneumonic effusion. Method: A cross-sectional study involving 250 inpatients with parapneumonic effusion, treated in a tertiary-care hospital between 1994 and 1999. The following variables were analyzed: clinical presentation, chest X-rays, pleural fluid culture and biochemical analysis of the pleural fluid, as well as the score and treatment. The score was based on four categories: general appearance of the pleural fluid, chest X-rays, laboratory findings, and the second thoracentesis. Drainage was recommended for patients scoring higher than 5.5. Results: Of 941 children with pneumonia, parapneumonic effusion occurred in 304 (32.2%), 250 of which were included in the study. Of those, 146 (58.4%) were male, with mean of age of 3 years (median, 2 years). The cutoff points (determined through receiver operating characteristic curve analysis) for suggesting pleural drainage were pH < 7.29 (89.2% sensitivity and 76.5% specificity), score > 5.0 (68.7% sensitivity and 81.7% specificity). These values were more strongly correlated with the need for drainage (p = 0.001), as were those reported in the literature (pH = 7.0 and glucose < 40). The lactate dehydrogenase did not prove to be a good parameter for indicating a need for drainage. Conclusion: In addition to the purulent aspect, pH = 7.29 and score were the best indicators of the need for chest-tube drainage in pediatric patients with parapneumonic effusion. However, we suggest that some score variables be readjusted to improve the usefulness of this particular scoring system.

Keywords: Empyema. Pleural effusion. Pneumonia.

Objective: To compare the expiratory flow increase technique (EFIT) and vibration accompanied by postural drainage (PD) in terms of their effects on the heart rate (HR), respiratory rate (RR) and SpO2 of infants with acute viral bronchiolitis (AVB). Methods: Infants with clinical and radiological diagnosis of AVB were analyzed. The HR, RR and SpO2 were registered at four time points: prior to the procedure; and at 10, 30 and 60 min after the procedure. The patients were divided into three groups: submitted to the EFIT; submitted to vibration/PD; and control. Results: We included 81 infants, 27 per group, with a mean age of 4.52 years and a mean weight of 6.56 kg. Using ANOVA, we found that the EFIT and vibration/PD groups presented no significant differences in relation to the control group in terms of the mean values for HR, RR or SpO2 (p > 0.05). Considering only the four time points evaluated, the mean RR was significantly lower in the EFIT and vibration/PD groups than in the control group (p < 0.05). Conclusions: In terms of overall improvement of cardiorespiratory parameters, neither the EFIT nor vibration/PD provided any benefit to infants with BVA. However, over time, respiratory physical therapy seems to contribute to decreasing the RR in these patients.

Keywords: Bronchiolitis, viral; Physical therapy modalities; Infant.

Objective: To determine the prevalence and the characteristics of Mycoplasma pneumoniae-related community-acquired pneumonia (CAP) and parapneumonic pleural effusion (PPE) in children and adolescents. Methods: This was a retrospective observational study involving 121 patients with CAP/PPE hospitalized in a tertiary referral hospital between 2000 and 2008, divided into six groups according to the etiologic agent (G1 to G6, respectively): M. pneumoniae with or without co-infection, in 44 patients (group 1); etiologic agents other than M. pneumoniae, in 77 (group 2); M. pneumoniae without co-infection, in 34 (group 3); Streptococcus pneumoniae, in 36 (group 4); Staphylococcus aureus, in 31 (group 5); and M. pneumoniae/S. pneumoniae co-infection, in 9 (group 6). Results: In comparison with group 2, group 1 showed higher frequencies of females, dry cough, and previous use of beta-lactam antibiotics; longer duration of symptoms prior to admission; and lower frequencies of use of mechanical ventilation and chest tube drainage. In comparison with groups 4 and 5, group 3 showed higher frequencies of previous use of beta-lactam antibiotics and dry cough; longer duration of symptoms prior to admission; a lower frequency of use of chest tube drainage; a higher mean age and a lower frequency of nausea/vomiting (versus group 4 only); and a lower frequency of use of mechanical ventilation (versus group 5 only). M. pneumoniae/S. pneumoniae co-infection increased the duration of symptoms prior to admission. Conclusions: In this sample, the prevalence of M. pneumoniae-related CAP/PPE was 12.75%. Although the disease was milder than that caused by other microorganisms, its course was longer. Our data suggest that M. pneumoniae-related CAP/PPE in children and adolescents should be more thoroughly investigated in Brazil.

Keywords: Pleural effusion; Empyema, pleural; Pneumonia; Mycoplasma pneumoniae.

This study carries out a descriptive and comparative analysis of the various types of cystic fibrosis severity scores described in the literature and contextualizes the origin and objective of each. A total of 16 scoring systems were found: 8 are used predominantly for clinical evaluation, 5 for radiographic findings, 2 for tomographic findings and 1 for scintigraphic findings. Despite the criticism and controversy regarding these instruments of assessment, they have contributed to a better understanding of the disease and to the development of more effective therapeutic procedures.

Keywords: Severity of illness index. Cystic fibrosis. Review literature.

Objective: To assess the quality of life (QoL) of patients with cystic fibrosis (CF) followed at a university referral center for CF. Methods: A cross-sectional study involving application of the Cystic Fibrosis Questionnaire (CFQ) and Shwachman score in CF patients between April of 2008 and June of 2009. Results: The sample consisted of 75 patients. The mean age was 12.5 ± 5.1 years (range, 6.1-26.4 years). The patients were divided into three groups by age in years: group I (< 12), II (12-14), and III (≥ 14). The highest and lowest CFQ scores were for the nutrition domain in group III (89.3 ± 16.2) and the social domain in group II (59.5 ± 22.3), respectively. Groups I and III differed significantly regarding the treatment domain (p = 0.001). Regarding Shwachman scores, there were significant differences between patients scoring ≤ 70 and those scoring > 70 in the social (group I; p = 0.045), respiratory (group II; p = 0.053), and digestive (p = 0.042) domains. In group III, severity did not correlate with QoL. In groups I and II, patients with an FEV1 < 80% of predicted did not differ from other patients for any CFQ domain. However, in group III, values for the following domains were significantly lower in patients with an FEV1 < 80%: physical (p = 0.012); body image (p = 0.031); respiratory (p = 0.023), emotional (p = 0.041); and social role (p = 0.024). Conclusions: It is important to assess QoL in CF patients, because it can improve treatment compliance.

Keywords: Cystic fibrosis; Quality of life; Questionnaires.

Objective: To identify associations between genetic polymorphisms (in the MBL2, TGF-β1 and CD14 genes) and the severity of the lung disease in patients with cystic fibrosis (CF), as well as between the presence of ΔF508 alleles and lung disease severity in such patients. Methods: This was a cross-sectional cohort study, based on clinical and laboratory data, involving 105 patients with CF treated at a university hospital in the 2005-2006 period. We included 202 healthy blood donors as controls for the determination of TGF-β1 and CD14 gene polymorphisms. Polymorphisms in the MBL2 and TGF-β1 genes at codon 10, position +869, were genotyped using the allele-specific PCR technique. The C-159T polymorphism in the CD14 gene was genotyped using PCR and enzymatic digestion. Results: Of the 105 CF patients evaluated, 67 presented with severe lung disease according to the Shwachman score. The MBL2 gene polymorphisms were not associated with disease severity in the CF patients. Analysis of the T869C polymorphism in the TGF-β1 gene showed an association only between TC heterozygotes and mild pulmonary disease. Although patients presenting the TT genotype of the C159T polymorphism in the CD14 gene predominated, there was no significant difference regarding lung disease severity. Conclusions: There was an association between the TC genotype of the T869C polymorphism (TGF-β1) and mild pulmonary disease in CF patients. In the CD14 gene, the TT genotype seems to be a risk factor for pulmonary disease but is not a modulator of severity. We found no association between being a ΔF508 homozygote and presenting severe lung disease.

Keywords: Cystic fibrosis; Polymorphism, genetic; Severity of illness index; Mannose-binding lectin; Transforming growth factor beta.

Objective: To evaluate submaximal exercise tolerance and respiratory muscle strength in relation to forward head posture (FHP) and respiratory mode in children, comparing mouth-breathing (MB) children with nasal-breathing (NB) children. Methods: This was a controlled, analytical cross-sectional study involving children in the 8-12 year age bracket with a clinical otorhinolaryngology diagnosis of MB, recruited between October of 2010 and January of 2011 from the Mouth Breather Clinic at the State University of Campinas Hospital de Clínicas, located in the city of Campinas, Brazil. The exclusion criteria were obesity, asthma, chronic respiratory diseases, heart disease, and neurological or orthopedic disorders. All of the participants underwent postural assessment and the six-minute walk test (6MWT), together with determination of MIP and MEP. Results: Of the 92 children in the study, 30 presented with MB and 62 presented with NB. In the MB group, the differences between those with moderate or severe FHP and those with normal head posture, in terms of the mean MIP, MEP and six-minute walk distance (6MWD), were not significant (p = 0.079, p = 0.622, and p = 0.957, respectively). In the NB group, the mean values of MIP and MEP were higher in the children with moderate FHP than in those with normal head posture (p = 0.003 and p = 0.004, respectively). The mean MIP, MEP, and 6MWD were lower in the MB group than in the NB group. Values of MIP and MEP were highest in the children with moderate FHP. Conclusions: Respiratory biomechanics and exercise capacity were negatively affected by MB. The presence of moderate FHP acted as a compensatory mechanism in order to improve respiratory muscle function.

Keywords: Mouth breathing; Posture; Exercise tolerance; Respiratory mechanics.

Objective: To determine the relevance of screening for the F508del mutation of the cystic fibrosis transmembrane conductance regulator gene as a first step in the genetic diagnosis of cystic fibrosis (CF) by associating the genotype with various clinical variables. Methods: We evaluated 180 CF patients regarding the F508del mutation. The clinical data were obtained from the medical records of the patients and from interviews with their parents or legal guardians. Results: Of the 180 patients studied, 65 (36.1%) did not carry the F508del mutation (group 0 [G0]), 67 (37.2%) were F508del heterozygous (G1), and 48 (26.7%) were F508del homozygous (G2). All three groups showed associations with the clinical variables. Homozygosis was associated with younger patients, younger age at CF diagnosis, and younger age at the first isolation of Pseudomonas aeruginosa (PA), as well as with higher prevalence of pancreatic insufficiency (PI) and non-mucoid PA (NMPA) colonization. In comparison with G1+G2 patients, G0 patients were older; first experienced clinical symptoms, digestive disease, and pulmonary disease at an older age; were older at CF diagnosis and at first PA isolation; and had a lower prevalence of PI and meconium ileus, as well as of colonization by NMPA, mucoid PA, and Burkholderia cepacia. In G1 patients, values were intermediate for age at CF diagnosis; age at first PA isolation, first pulmonary symptoms, and first clinical manifestations; MPA colonization; and OR for PI. Conclusions: The identification of F508del in 63.9% of the patients studied showed that this can be a useful tool as a first step in the genetic diagnosis of CF. The F508del genotype was associated with clinical severity of the disease, especially with the variables related to CF onset.

Keywords: Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Genotype; Mutation.

Objective: To determine the frequency of six mutations (F508del, G542X, G551D, R553X, R1162X, and N1303K) in patients with cystic fibrosis (CF) diagnosed, at a referral center, on the basis of abnormal results in two determinations of sweat sodium and chloride concentrations. Methods: This was a cross-sectional study involving 70 patients with CF. The mean age of the patients was 12.38 ± 9.00 years, 51.43% were female, and 94.29% were White. Mutation screening was performed with polymerase chain reaction (for F508del), followed by enzymatic digestion (for other mutations). Clinical analysis was performed on the basis of gender, age, ethnicity, pulmonary/gastrointestinal symptoms, and Shwachman-Kulczycki (SK) score. Results: All of the patients showed pulmonary symptoms, and 8 had no gastrointestinal symptoms. On the basis of the SK scores, CF was determined to be mild, moderate, and severe in 22 (42.3%), 17 (32.7%), and 13 (25.0%) of the patients, respectively. There was no association between F508del mutation and disease severity by SK score. Of the 140 alleles analyzed, F508del mutation was identified in 70 (50%). Other mutations (G542X, G551D, R553X, R1162X, and N1303K) were identified in 12 (7.93%) of the alleles studied. In F508del homozygous patients with severe disease, the OR was 0.124 (95% CI: 0.005-0.826). Conclusions: In 50% of the alleles studied, the molecular diagnosis of CF was confirmed by identifying a single mutation (F508del). If we consider the analysis of the six most common mutations in the Brazilian population (including F508del), the molecular diagnosis was confirmed in 58.57% of the alleles studied.

Objective: To determine, in a sample of infants, the prevalence of and risk factors for occasional wheezing (OW) and recurrent wheezing-wheezy baby syndrome (WBS). Methods: Parents of infants (12-15 months of age) completed the International Study of Wheezing in Infants questionnaire. Results: We included 1,269 infants residing in the city of Blumenau, Brazil. Of those, 715 (56.34%) had a history of wheezing, which was more common among boys. The prevalences of OW and WBS were 27.03% (n = 343) and 29.31% (n = 372), respectively. On average, the first wheezing episode occurred at 5.55 ± 2.87 months of age. Among the 715 infants with a history of wheezing, the first episode occurred within the first six months of life in 479 (66.99%), and 372 (52.03%) had had three or more episodes. Factors associated with wheezing in general were pneumonia; oral corticosteroid use; a cold; attending daycare; having a parent with asthma or allergies; mother working outside the home; male gender; no breastfeeding; and mold. Factors associated with WBS were a cold; physician-diagnosed asthma; ER visits; corticosteroid use; pneumonia; bronchitis; dyspnea; attending daycare; bronchodilator use; having a parent with asthma; no breastfeeding; mother working outside the home; and a dog in the household. Conclusions: The prevalence of wheezing in the studied population was high (56.34%). The etiology was multifactorial, and the risk factors were intrinsic and extrinsic (respiratory tract infections, allergies, attending daycare, and early wheezing). The high prevalence and the intrinsic risk factors indicate the need and the opportunity for epidemiological and genetic studies in this population. In addition, mothers should be encouraged to prolong breastfeeding and to keep infants under six months of age out of daycare.

Keywords: Asthma; Prevalence; Risk factors.

Objective: To describe the clinical manifestations and bronchoscopic treatment of foreign body aspiration in children under 14 years of age, correlating the clinical aspects with the bronchoscopic findings. Methods: A retrospective, descriptive study analyzing data related to children under 14 years of age undergoing bronchoscopy due to clinical suspicion of foreign body aspiration at the State University at Campinas Hospital das Clinicas from January of 2000 to December of 2005. Results: The sample consisted of 69 patients, ranging in age from 8 months to 12 years/7 months (75.4% under 3 years of age), 62.3% of whom were male. The principal complaint was sudden-onset cough (75.4%), auscultation was abnormal in 74%, and dyspnea was observed in 29%. Radiological abnormalities were seen in 88% of the cases. Aspirations were primarily into the right lung (54.8%), and 30.7% of the foreign bodies were of vegetal origin (principally beans and peanuts). In the follow-up period, 29% presented complications (most commonly pneumonia), which were found to be associated with longer aspiration time (p = 0.03). Mechanical ventilation was required in 7 children (10.1%), and multiple bronchoscopies were performed in 5 (7.2%). Conclusion: A history of sudden-onset choking and cough, plus abnormal auscultation and radiological findings, characterizes the profile of foreign body aspiration. In such cases, bronchoscopy is indicated. Longer aspiration time translates to a higher the risk of complications. The high prevalence of foreign bodies of vegetal origin underscores the relevance of prevention programs aimed at children younger than 3 years of age.

Keywords: Foreign bodies; Bronchoscopy; Pediatrics.

The growth of children with asthma has attracted great interest because it is a chronic respiratory illness whose prevalence in childhood has increased during the last decades. The relationship between asthma and growth has been studied for a long time, but the great variability of diagnosis, therapy, and different methods of investigation make it difficult to disentangle the factors that are responsible for the growth retardation detected by some authors. As a result of different observations, there remain many doubts about the impact of asthma on child and adolescent growth. The aim of this paper is to provide a general view on the issue.

Objective: To compare patients with cystic fibrosis and healthy individuals in terms of their functional performance on the six-minute walk test (6MWT). Methods: A prospective, cross-sectional study involving healthy individuals and patients with cystic fibrosis treated at a referral university hospital in the city of Campinas, Brazil. The 6MWT was administered in accordance with the American Thoracic Society guidelines, and it was repeated after a 30-min rest period. For all of the participants, RR, HR, SpO2, and Borg scale scores were obtained. For the cystic fibrosis patients, nutritional status and spirometric values were determined. Patients with pulmonary exacerbation were excluded. Spearman's correlation coefficient and repeated measures ANOVA were used. Results: The cystic fibrosis group comprised 55 patients, and the control group comprised 185 healthy individuals. The mean ages were 12.2 ± 4.3 and 11.3 ± 4.3 years, respectively. The six-minute walk distance (6MWD) was significantly shorter in the cystic fibrosis group than in the control group for both tests (547.2 ± 80.6 m vs. 610.3 ± 53.4 m for the first and 552.2 ± 82.1 m vs. 616.2 ± 58.0 m for the second; p < 0.0001 for both). The 6MWD correlated with age, weight, and height only in the cystic fibrosis group. During the tests, SpO2 remained stable, whereas HR and RR increased. Conclusions: In our sample, functional performance on the 6MWT was poorer among the cystic fibrosis patients than among the healthy controls in the same age bracket, and we found immediate repetition of the test to be unadvisable.

Keywords: Cystic fibrosis; Exercise tolerance; Dyspnea.

Objective: To evaluate whether respiratory therapy followed by the use of inhaled albuterol modifies the pulmonary deposition of inhaled tobramycin in patients with cystic fibrosis (CF) and whether pulmonary deposition correlates with disease severity or genotype. Methods: A prospective study was carried out including patients with CF older than 6 years of age and colonized with Pseudomonas aeruginosa. Exclusion criteria were pulmonary exacerbation, changes in therapy between the study phases and FEV1 < 25%. All patients were submitted to pulmonary scintigraphy by means of a scintillation camera equipped with a low-energy all-purpose collimator in order to evaluate drug penetration following the administration of inhaled 99mTc-tobramycin, as well as to pulmonary perfusion with 99mTc-macroaggregated albumin (phase 1). One month later, the same procedure was performed following respiratory therapy and administration of inhaled albuterol (phase 2). Results: We included 24 patients (12 males) aged 5-27 years (mean ± SD: 12.85 ± 6.64 years). The Shwachman score (SS) was excellent/good in 8 patients, moderate/fair in 16 and poor in 0. Genotyping revealed that 7 patients were ΔF508 homozygotes, 13 were ΔF508 heterozygotes; and 4 presented other mutations. In all patients, lung deposition of tobramycin decreased in phase 2, especially in those with moderate/fair SS (p = 0.017) and in heterozygotes (p = 0.043). Conclusions: The use of a respiratory therapy technique and the administration of inhaled albuterol immediately prior to the use of inhaled tobramycin decreased the pulmonary deposition of the latter in CF patients, and this reduction correlates with disease severity and genotype.

Keywords: Cystic fibrosis; Tobramycin; Respiratory therapy; Albuterol; Radionuclide imaging.

Evidence-based techniques have been increasingly used in the creation of clinical guidelines and the development of recommendations for medical practice. The use of levels of evidence allows the reader to identify the quality of scientific information that supports the recommendations made by experts. The objective of this review was to address current concepts related to the clinical impact, diagnosis, and treatment of Pseudomonas aeruginosa infections in patients with cystic fibrosis. For the preparation of this review, the authors defined a group of questions that would be answered in accordance with the principles of PICO-an acronym based on questions regarding the Patients of interest, Intervention being studied, Comparison of the intervention, and Outcome of interest. For each question, a structured review of the literature was performed using the Medline database in order to identify the studies with the methodological design most appropriate to answering the question. The questions were designed so that each of the authors could write a response. A first draft was prepared and discussed by the group. Recommendations were then made on the basis of the level of scientific evidence, in accordance with the classification system devised by the Oxford Centre for Evidence-Based Medicine, as well as the level of agreement among the members of the group.

Keywords: Cystic fibrosis/diagnosis; Cystic fibrosis/drug therapy; Pseudomonas aeruginosa; Evidence-based medicine.