Pulmonary outcome in former preterm, very low birth weight children with bronchopulmonary dysplasia: a case-control follow-up at school age.

OBJECTIVE: To assess and compare long-term pulmonary outcomes in former preterm-born, very low birth weight (VLBW) children with and without bronchopulmonary dysplasia (BPD) born in the surfactant era. STUDY DESIGN: Pulmonary function tests (ie, spirometry, body plethysmography, and gas transfer testing) were performed in children with a history of VLBW and BPD (n = 28) and compared with a matched preterm-born VLBW control group (n = 28). Medical history was evaluated by questionnaire. RESULTS: At time of follow-up (mean age, 9.5 years), respiratory symptoms (36% vs 8%) and receipt of asthma medication (21% vs 0%) were significantly more frequent in the preterm-born children with previous BPD than in those with no history of BPD. The children with a history of BPD had significantly lower values for forced expiratory volume in 1 second (z-score -1.27 vs -0.4; P = .008), forced vital capacity (z-score -1.39 vs -0.71 z-score; P = .022), and forced expiratory flow rate at 50% of forced vital capacity (z-score -2.21 vs -1.04; P = .048) compared with the preterm control group. CONCLUSION: Preterm-born children with a history of BPD are significantly more likely to have lung function abnormalities, such as airway obstruction and respiratory symptoms, at school age compared with preterm-born children without BPD.

Considerations and pitfalls in phenotyping and reclassification of chronic obstructive pulmonary disease.

As the clinical and research focus of chronic obstructive pulmonary disease (COPD) evolves from regarding obstructive lung disease as a single disease entity to recognizing the complexity of disease expression, the importance of COPD phenotyping rises to the forefront. The reclassification of COPD holds both prognostic and therapeutic implications but does not come without issues that may complicate classification efforts. In this review, we discuss the significance of refining the definition of the term phenotype, consider the impact of variations in cohort severity and attribute mix, account for the contrast of longitudinal vs cross-sectional cohort analysis, recognize the differing criteria used to define disease traits along with the nuances of combining cohorts, and identify the interaction of covariates as we advance in the field of COPD phenotyping.

Probability of treatment following acute decline in lung function in children with cystic fibrosis is related to baseline pulmonary function.

OBJECTIVE: To determine whether the association between high forced expiratory volume in 1 second (FEV1) and increased rate of decline in FEV1 in children with cystic fibrosis could be due to less frequent intervention after acute declines (sudden decline events) in FEV1. STUDY DESIGN: Patients with cystic fibrosis aged 6-17 years enrolled in the Epidemiologic Study of Cystic Fibrosis were assessed for a sudden decline event, defined as a 10% relative decline in FEV1% predicted from an average of 3 consecutive stable baseline spirometries. The likelihood of therapeutic intervention within 14 days before and 56 days after this event was then related to their baseline FEV1% predicted age-specific decile using a logistic regression adjusting for age group (6-12 years, 13-17 years) and presence of Pseudomonas aeruginosa on respiratory culture. RESULTS: A total of 10 888 patients had at least 1 sudden decline event in FEV1. Patients in the highest FEV1 decile were significantly less likely than those in the lowest decile to receive intravenous antibiotics (OR, 0.14; 95% CI, 0.11-0.18; P < .001) or be hospitalized (OR, 0.18; 95% CI, 0.14-0.23; P < .001) following decline. CONCLUSIONS: Children and adolescents with high baseline lung function are less likely to receive a therapeutic intervention following an acute decline in FEV1, which may explain their greater rate of FEV1 decline.

Energy expenditure and nutritional status in pediatric patients before and after lung transplantation.

Resting energy expenditure and nutritional status in pediatric patients was determined before and then 1 and 2 years after lung transplantation. Mean resting energy expenditure was increased (132%) before transplantation and declined (112%) after transplantation. Body mass index and weight z-scores improved posttransplantation, but nutritional measurements remained below normal population values.

Stimulated nitric oxide production and arginine deficiency in children with cystic fibrosis with nutritional failure.

OBJECTIVE: To determine whether upregulated whole body de novo arginine synthesis and protein breakdown are present as a compensatory mechanism to meet the increased demand for arginine and nitric oxide (NO) production in pediatric patients with cystic fibrosis (CF) and nutritional failure. STUDY DESIGN: In 16 children with CF, studied at the end of antibiotic treatment for a pulmonary exacerbation, and 17 healthy controls, whole body arginine, citrulline (Cit), and protein turnover were assessed by stable isotope methodology and de novo arginine synthesis, arginine clearance, NO synthesis, protein synthesis and breakdown, and net protein balance were calculated. The plasma isotopic enrichments and amino acid concentrations were measured by liquid chromatography-tandem mass spectrometry. RESULTS: Increased arginine clearance was found in patients with CF (P < .001), whereas whole body NO production rate and plasma arginine levels were not different. Whole body arginine production (P < .001), de novo arginine synthesis, and protein breakdown and synthesis (P < .05) were increased in patients with CF, but net protein balance was comparable. Patients with CF with nutritional failure (n = 7) had significantly higher NO production (P < .05), de novo arginine synthesis, Cit production (P < .001), and plasma Cit concentration (P < .05) and lower plasma arginine concentration (P < .05) than those without nutritional failure (n = 9). CONCLUSIONS: Nutritional failure in CF is associated with increased NO production. However, up-regulation of de novo arginine synthesis and Cit production was not sufficient to meet the increased arginine needs leading to arginine deficiency.

Effectiveness of pulmonary rehabilitation in exercise capacity and quality of life in chronic obstructive pulmonary disease patients with and without global fat-free mass depletion.

OBJECTIVE: To investigate the effectiveness of pulmonary rehabilitation (PR) in exercise capacity and quality of life in patients with chronic obstructive pulmonary disease (COPD) with and without global fat-free mass (FFM) depletion. DESIGN: Retrospective case-control. SETTING: Outpatient clinic, university center. PARTICIPANTS: COPD patients (N=102) that completed PR were initially evaluated. INTERVENTION: PR including whole-body and weight training for 12 weeks, 3 times per week. MAIN OUTCOME MEASURES: St. George Respiratory Questionnaire (SGRQ), 6-minute walk distance (6MWD), and FFM evaluation applied before and after PR. RESULTS: Patients were stratified according to their FFM status measured by bioelectric impedance. They were considered depleted if the FFM index was ≤ 15 kg/m(2) in women and ≤ 16 kg/m(2) in men. From the initial sample, all depleted patients (n=31) composed the FFM depleted group. It was composed predominantly by women (68%) with a mean age ± SD of 64.4 ± 7.3 years and a forced expiratory volume in 1 second of 33.6%=-13.2% predicted. Paired for sex and age, 31 nondepleted patients were selected from the initial sample to compose the nondepleted group. Improvement in the 6MWD was similar in these 2 groups after PR. Both groups improved SGRQ scores, although the observed power was small and did not allow adequate comparison between depleted and nondepleted patients. There was no difference between groups in weight change, whereas FFM tended to be greater in depleted patients. This increase had no correlation with the 6MWD or the SGRQ. CONCLUSIONS: Benefits of PR to exercise capacity were similar comparing FFM depleted and nondepleted COPD patients. Although FFM change tended to be greater in depleted patients, this increase had no definite relation with clinical outcomes.

Análise de covariância: uma aplicação a dados de função pulmonar, ajustados por idade / Analysis of covariance: application to pulmonary function data, adjusted for age

Introdução: Em diversas situações estamos interessados em comparar médias entre dois ou mais grupos. A relação entre estas variáveis pode ser influenciada por uma terceira variável. Esta última é conhecida como covariável e deve ser incluída na análise estatística. Quando essa variável é quantitativa utiliza-se Análise de Covariância (ANCOVA). No contexto da fibrose cística (FC), o volume expiratório forçado no primeiro segundo (VEF1) é uma medida de função pulmonar conhecida por desempenhar importante papel na monitorização de pacientes. Estudos mostram que mulheres com FC apresentaram valores mais baixos de VEF1. Entretanto, a influência da idade também deve ser considerada. Objetivo: Apresentar a aplicabilidade da ANCOVA, suas suposições e a interpretação de seus resultados, através de um exemplo envolvendo a relação entre VEF1 e gênero, considerando a idade dos pacientes como covariável. Métodos: Foram utilizados dados obtidos por simulação, considerando VEF1 com distribuição normal (média=86; DP=21). ANCOVA foi utilizada para avaliar diferença média de VEF1 entre homens e mulheres, ajustada por idade.Resultados: Foram analisados dados de 64 pacientes, idade média de 12 anos (DP=2,5) e VEF1 médio de 85,9 (DP=20,73). Na avaliação inicial do VEF1, as mulheres apresentaram, em média, valores significativamente maiores do que os homens (P=0,021). Entretanto, após o ajuste por idade, esta relação deixou de ser significativa (P=0,100). Conclusão: Esses dados ilustram a influência de uma covariável na relação entre um fator em estudo e o desfecho. Verificou-se a partir da ANCOVA, que o efeito aparente de gênero no VEF1 desaparece com o ajuste para idade do paciente.

Background: In several situations there is an interest in comparing means between two or more groups. The relationship between these variables may be influenced by a third variable, known as covariate, which should be included in the statistical analysis. When the covariate is a quantitative variable, analysis of covariance (ANCOVA) should be used. In the context of cystic fibrosis (CF), forced expiratory volume in 1 second (FEV1) is a measure of pulmonary function known to play an important role in patient monitoring. Studies have shown that women with CF have lower FEV1. However, the influence of age should also be considered. Aim: To demonstrate the applicability of ANCOVA, with assumptions and interpretation of results, using an example involving the relationship between FEV1 and gender, considering patient age as a covariate. Methods: Data were obtained by simulation, considering FEV1 as normally distributed (mean=86; SD=21). ANCOVA was used to assess mean differences in FEV1 between men and women, adjusted for age. Results: Data from 64 patients [mean age: 12 years (SD=2.5)] were analyzed, and mean FEV1 was 85.9 (SD=20.73). At baseline, women had average FEV1 values significantly higher than men (P=0.021). However, after adjusting for age, this relationship was no longer significant (P=0.100). Conclusion: These data illustrate the influence that a covariate may have on the relationship between factors under study and the outcome of interest. ANCOVA revealed that the apparent effect of gender on FEV1 disappears after adjustment for patient age.