Objective: Although various strategies have been proposed for eradicating Pseudomonas aeruginosa in patients with cystic fibrosis (CF), only a few employ multistep treatment in children colonized by that pathogen for the first time. The aim of this study was to describe the effectiveness of a three-phase eradication protocol, initiated after the first isolation of P. aeruginosa, in children with CF in Brazil. Methods: This was a retrospective real-life study in which we reviewed the medical records of pediatric CF patients in whom the eradication protocol was applied between June of 2004 and December of 2012. The three-phase protocol was guided by positive cultures for P. aeruginosa in airway secretions, and the treatment consisted of inhaled colistimethate and oral ciprofloxacin. Success rates were assessed after each phase, as well as cumulatively. Results: During the study period, 47 episodes of P. aeruginosa colonization, in 29 patients, were eligible for eradication. Among the 29 patients, the median age was 2.7 years, 17 (59%) were male, and 19 (65%) had at least one F508del allele. All 29 patients completed the first phase of the protocol, whereas only 12 and 6 completed the second and third phases, respectively. Success rates for eradication in the three treatment phases were 58.6% (95% CI: 40.7-74.5), 50.0% (95% CI: 25.4-74.6), and 66.7% (95% CI: 30.0-90.3), respectively. The cumulative success rate was 93.1% (95% CI: 78.0-98.1). Treatment failure in all three phases occurred in only 2 patients. Conclusions: In this sample of patients, the multistep eradication protocol was effective and had a high success rate.

Keywords: Cystic fibrosis/therapy; Cystic fibrosis/prevention & control; Pseudomonas aeruginosa; Treatment outcome.

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.

Objective: To identify microorganisms in sputum samples of patients with stable non-cystic fibrosis bronchiectasis and to determine risk factors related to the isolation of Pseudomonas aeruginosa (PA) in those patients. Methods: Consecutive patients were recruited from a tertiary hospital outpatient clinic in the city of Fortaleza, Brazil. The patients were submitted to spirometry, six-minute walk test, HRCT, and sputum collection. Data on serum fibrinogen levels, disease severity, sputum color, and history of azithromycin treatment were collected. Results: The study included 112 patients, and females predominated (68%). The mean age was 51.6 ± 17.4 years. Most patients presented with mild-to-moderate disease (83%). The mean six-minute walk distance was 468.8 ± 87.9 m. Mean FEV1 and FVC, in % of predicted values, were 60.4 ± 21.8% and 69.9 ± 18.5%, respectively. The mean serum fibrinogen level was 396.1 ± 76.3 mg/dL. PA was isolated in 47 patients, other potentially pathogenic microorganisms (PPMs) were isolated in 31 patients, and non-PPMs were isolated in 34 patients. Purulent sputum was identified in 77 patients (68%). The patients with PA, when compared with those without it, presented with more severe disease, higher serum fibrinogen levels, and lower FVC%. In addition, purulent sputum and long-term azithromycin treatment were more common in those with PA. The multivariate regression analysis showed that the independent factors associated with PA were serum fibrinogen level > 400 mg/dL (OR = 3.0; 95% CI: 1.1-7.7) and purulent sputum (OR = 4.3; 95% CI: 1.6-11.3). Conclusions: In our sample, the prevalence of PA in sputum was 42%. Sputum color and inflammatory markers were able to predict the isolation of PA, emphasizing the importance of routine sputum monitoring.

Keywords: Bronchiectasis; Pseudomonas aeruginosa; Sputum/microbiology.

Objective: To compare HRCT findings in cystic fibrosis (CF) patients chronically colonized with Pseudomonas aeruginosa or Staphylococcus aureus using the modified Bhalla CT scoring system, as well as to evaluate intraobserver and interobserver reliability of the method. Methods: This was a retrospective cross-sectional study involving 41 CF patients, 26 of whom were chronically colonized with P. aeruginosa (Pa group), and 15 of whom were colonized with S. aureus (Sa group).Two independent radiologists evaluated the HRCT scans of these patients using the modified Bhalla CT scoring system in two different moments. Intraobserver and interobserver reliability was calculated using the intraclass correlation coefficient (ICC). Results: There was good intraobserver and interobserver agreement (ICC > 0.8). Scores were higher in the Pa group than in the Sa group for observer 1 (mean, 13.50 ± 3.90; median, 13.5 vs. mean, 5.00 ± 5.28; median, 3.0) and for observer 2 (mean, 11.96 ± 5.07; median, 12.0 vs. mean, 5.07 ± 5.65; median, 5.0). In addition, HRCT findings, such as bronchiectasis, bronchial wall thickening, mucus plugging, generation of bronchial divisions, and mosaic attenuation/perfusion pattern, were more prevalent in the Pa group. Conclusions: The modified Bhalla CT scoring system was reproducible and reliable for use in the evaluation of HRCT scans, allowing distinctions to be drawn between the two groups of patients under study. The higher scores in the Pa group provided evidence of greater pulmonary impairment in that group.

Keywords: Cystic fibrosis; Tomography; Staphylococcus aureus; Pseudomonas aeruginosa.

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.

Objectives: To characterize the main identified mutations on cystic fibrosis transmembrane conductance regulator (CFTR) in a group of children and adolescents at a cystic fibrosis center and its association with the clinical and laboratorial characteristics. Method: Descriptive cross-sectional study including patients with cystic fibrosis who had two alleles identified with CFTR mutation. Clinical, anthropometrical, laboratorial and pulmonary function (spirometry) data were collected from patients' records in charts and described with the results of the sample genotyping. Results: 42 patients with cystic fibrosis were included in the study. The most frequent mutation was F508del, covering 60 alleles (71.4%). The second most common mutation was G542X (six alleles, 7.1%), followed by N1303K and R1162X mutations (both with four alleles each). Three patients (7.14%) presented type III and IV mutations, and 22 patients (52.38%) presented homozygous mutation for F508del. Thirty three patients (78.6%) suffered of pancreatic insufficiency, 26.2% presented meconium ileus, and 16.7%, nutritional deficit. Of the patients in the study, 59.52% would be potential candidates for the use of CFTR-modulating drugs. Conclusions: The mutations of CFTR identified more frequently were F508del and G542X. These are type II and I mutations, respectively. Along with type III, they present a more severe cystic fibrosis phenotype. More than half of the sample (52.38%) presented homozygous mutation for F508del, that is, patients who could be treated with Lumacaftor/Ivacaftor. Approximately 7% of the patients (7.14%) presented type III and IV mutations, therefore becoming candidates for the treatment with Ivacaftor.

Keywords: Cystic fibrosis; Mutations; Genetics; Phenotype; Child

Objective: To determine the prevalence of nocturnal hypoxemia and its association with pulmonary function, nutritional status, sleep macrostructure, and obstructive respiratory events during sleep in a population of clinically stable children and adolescents with cystic fibrosis (CF). Methods: This was a cross-sectional study involving 67 children and adolescents with CF between 2 and 14 years of age. All of the participants underwent polysomnography, and SpO2 was measured by pulse oximetry. We also evaluated the Shwachman-Kulczycki (S-K) scores, spirometry findings, and nutritional status of the patients. Results: The study involved 67 patients. The mean age of the patients was 8 years. The S-K scores differed significantly between the patients with and without nocturnal hypoxemia, which was defined as an SpO2 < 90% for more than 5% of the total sleep time (73.75  6.29 vs. 86.38  8.70; p < 0.01). Nocturnal hypoxemia correlated with the severity of lung disease, FEV1 (rs = −0.42; p = 0.01), FVC (rs = −0.46; p = 0.01), microarousal index (rs = 0.32; p = 0.01), and apnea-hypopnea index (rs = 0.56; p = 0.01). Conclusions: In this sample of patients with CF and mild-to-moderate lung disease, nocturnal oxygenation correlated with the S-K score, spirometry variables, sleep macrostructure variables, and the apnea-hypopnea index.

Keywords: Cystic fibrosis; Sleep; Oximetry.

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.

Objective: Depression and anxiety have been documented in people with cystic fibrosis (CF), jeopardizing treatment adherence. To date, no studies have assessed the prevalence of psychosocial issues in adolescents with CF in Brazil. We sought to assess the prevalence of depression and anxiety in adolescents with CF in Brazil, as well as the impact of depression and anxiety on treatment adherence. Methods: This was a multicenter, prospective, observational, longitudinal study conducted between 2017 and 2019 at 14 CF referral centers in Brazil. We used standardized tools such as the nine-item Patient Health Questionnaire (for depression), the seven-item Generalized Anxiety Disorder scale (for anxiety), and the eight-item Morisky Medication Adherence Scale (for treatment adherence) in order to collect data on 218 CF patients at two different time points. Results: The prevalence of depression was 19.1% at time point 1 and 15.4% at time point 2. The prevalence of anxiety was 19.1% at time point 1 and 18.0% at time point 2. Depression and anxiety were significantly higher in female patients and lower in those who underwent home physiotherapy or had psychological support. Significant correlations were found between depression and anxiety at both time points, the associations being strongest at time point 1 (r = 0.68; p < 0.001). Most (66.7%) of the study participants reported low adherence to treatment, and the remainder reported either average adherence (in 28%) or high adherence (in 5.3%). Depression and anxiety showed inverse correlations with treatment adherence. Conclusions: The prevalence of depression and anxiety in adolescents with CF in Brazil appears to be similar to that reported in other countries, being higher in females and lower in those undergoing home physiotherapy or receiving psychological care. Depression and anxiety appear to correlate with lower treatment adherence. Treating psychosocial issues may effectively improve rates of treatment adherence in adolescents with CF.

Keywords: Cystic fibrosis; Anxiety; Depression; Treatment adherence and compliance; Adolescent.

Objectives: To evaluate the self-reported degree of adherence to treatment in patients with cystic fibrosis (CF), investigating associations with characteristics of the disease and with the degree of adherence perceived by health professionals. Methods: This was a prospective, cross-sectional study involving patients with CF monitored at a Program for Adults with CF. The degree of adherence was evaluated using a questionnaire. Patients were divided into two groups: greater degree of adherence and moderate/poor degree of adherence. Clinical data, Shwachman-Kulczycki clinical score, Brasfield radiographic score and spirometry data were obtained for all patients. Results: Out of 38 patients studied, 31 (81.6%) were classified as presenting a greater degree of adherence and 7 (18.4%) as presenting a moderate/poor degree of adherence. The self-reported patient adherence score correlated with the clinical score (r = −0.36, p = 0.028). The self-reported patient adherence score (median = 0.79) was higher than that perceived by health professionals (median = 0.71, p = 0.003). A greater degree of adherence was self-reported for respiratory therapy (by 84.2%), exercise (by 21.1%), prescribed diet (by 65.8%), pancreatic enzymes (by 96.3%), vitamins (by 79.4%), inhaled antibiotic therapy (by 76.7%) and inhaled DNase (by 79.4%). Conclusions: Self-reported adherence of patients attending a Program for Adults with CF was good. The self-reported patient adherence score correlated inversely with the clinical score. Self-reported patient adherence was greater than the adherence perceived by health professionals.

Keywords: Cystic fibrosis; Patient compliance; Therapeutics.

Objective: To determine the prevalence of allergic bronchopulmonary aspergillosis (ABPA) in patients with cystic fibrosis treated at a referral center in the state of Bahia, Brazil. Methods: A cross-sectional study, with prospective data collection, carried out at the Cystic Fibrosis Referral Center of Bahia of the Octávio Mangabeira Specialized Hospital. We evaluated 74 patients diagnosed with cystic fibrosis, older than six years of age, treated between December 9, 2003 and March 7, 2005. We analyzed the following variables: gender, age, forced vital capacity, forced expiratory volume in one second, pharmacodynamic response, chest X-ray findings, facial sinus X-ray findings, wheezing, cultures for Aspergillus spp., total immunoglobulin E (IgE), specific IgE for Aspergillus fumigatus and immediate skin test reactivity to A. fumigatus antigen. Results: Of the 74 patients, 2 were diagnosed with ABPA. We found total IgE levels > 1,000 IU/mL in 17 (23%), positive immediate skin reactivity to A. fumigatus antigen in 19 (25.7%) and wheezing in 60 (81.1%). Conclusions: The prevalence of ABPA was 2.7%. The high levels of total IgE, high incidence of wheezing and high rate of immediate skin test reactivity to A. fumigatus antigen suggest that these patients should be carefully monitored due to their propensity to develop ABPA.

Keywords: Cystic fibrosis; Aspergillosis, allergic bronchopulmonary; Immunoglobulin E/diagnostic use; Hypersensitivity, immediate/diagnosis; Gliotoxin.

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 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 evaluate the perception of disease severity in patients with cystic fibrosis (CF), investigating its relationship with clinical score, radiographic score, respiratory function tests, adherence to treatment and perception of self-care practices. Methods: Prospective, cross-sectional study involving CF patients treated in a program for adults with CF. The perception of disease severity, adherence to treatment and reported self-care practices were evaluated by means of questionnaires. Clinical data, Shwachman-Kulczycki clinical score, Brasfield radiographic score and spirometry were obtained for all of the patients. Results: Of the 38 patients studied, 3 (7.9%) patients rated their perception of health status as well below average; 5 (13.2%), as below average; 15 (39.5%), as average; 10 (26.3%), as above average; and 5 (13.2%), as well above average. The perception of disease severity correlated significantly with clinical score (r = 0.43, p = 0.007), FVC (r = 0.34, p = 0.034), FEV1 (r = 0.38, p = 0.019) and self-care practices (r = 0.33, p = 0.044), but not with degree of adherence (r = -0.03, p = 0.842) and radiographic score (r = 0.33, p = 0.51). Conclusions: The perception of disease severity correlated with objective measurements of disease severity (clinical score and respiratory function tests) and with reported self-care practices, but not with adherence to treatment.

Keywords: Severity of illness index; Cystic fibrosis; Patient compliance; Respiratory function tests.