Spirometry in 3-5-year-old children with asthma

Spirometry with incentive games was applied to 207 2-5-year-old preschool children (PSC) with asthma in order to refine the quality-control criteria proposed by Aurora et al. (Am J Respir Crit Care Med 2004;169:1152-159). The data set in our study was much larger compared to that in Aurora et al. (Am J Respir Crit Care Med 2004;169:1152-159), where 42 children with cystic fibrosis and 37 healthy control were studied. At least two acceptable maneuvers were obtained in 178 (86%) children. Data were focused on 3-5-year-old children (n = 171). The proportion of children achieving a larger number of thresholds for each quality-control criterion (backward-extrapolated volume (Vbe), Vbe in percent of forced vital capacity (FVC, Vbe/FVC), time-to-peak expiratory flow (time-to-PEF), and difference (Delta) between the two FVCs (DeltaFVC), forced expiratory volume in 1 sec (DeltaFEV(1)), and forced expiratory volume in 0.5 sec (DeltaFEV(0.5)) from the two "best" curves) was calculated, and cumulative plots were obtained. The optimal threshold was determined for all ages by derivative function of rate of success-threshold curves, close to the inflexion point. The following thresholds were defined for acceptability: Vbe 相似文献   

Lung function in 3-5-year-old children with cystic fibrosis

It is well established that the lung disease of CF can occur early in life and may progress through the preschool years when accurate lung function assessment has been challenging to perform. We hypothesized that respiratory inductive plethysmography (RIP) and spirometry could be effectively performed in 3-6-year-old children and could be used to assess both longitudinal changes in lung function and the acute changes that occur during exacerbation of pulmonary disease. Both RIP and spirometry were equally feasible; however, the success rate for spirometry gradually increased with age to become higher than that for RIP in the 6-year-old subjects. Forty-four subjects were studied longitudinally and demonstrated significant increases in FVC, FEV(1), and FEV(0.5), but not in FEF(25-75) or RIP variables. There were significant differences in FVC, FEV(1), and phase angle (a measure of thoracoabdominal asynchrony) during exacerbations of lung disease. Although both RIP and spirometry were able to show differences in lung function in subjects with acute clinical worsening, spirometry was more robust in demonstrating change in lung function longitudinally and in children who had an exacerbation of lung disease.     

Spirometry in early childhood in cystic fibrosis patients

BACKGROUND: Spirometry data in cystic fibrosis (CF) patients in early childhood is scarce, and the ability of spirometry to detect airways obstruction is debatable. OBJECTIVE: To evaluate the ability of spirometry to detect airflow obstruction in CF patients in early childhood. METHODS: CF children (age range, 2.5 to 6.9 years) in stable clinical condition were recruited from five CF centers. The children performed guided spirometry (SpiroGame; patented by Dr. Vilzone, 2003). Spirometry indices were compared to values of a healthy early childhood population, and were analyzed with relation to age, gender, and clinical parameters (genotype, pancreatic status, and presence of Pseudomonas in sputum or oropharyngeal cultures). RESULTS: Seventy-six of 93 children tested performed acceptable spirometry. FVC, FEV1, forced expiratory flow in 0.5 s (FEV0.5), and forced expiratory flow at 50% of vital capacity (FEF50) were significantly lower than healthy (z scores, mean +/- SD: - 0.36 +/- 0.58, - 0.36 +/- 0.72, - 1.20 +/- 0.87; and - 1.80 +/- 1.47, respectively; p < 0.01); z scores for FEV1 and FVC were similar over the age ranges studied. However, z scores for FEV0.5 and forced expiratory flow at 25 to 75% of vital capacity were significantly lower in older children compared to younger children (p < 0.001), and a higher proportion of 6-year-old than 3-year-old children had z scores that were > 2 SDs below the mean (65% vs 5%, p < 0.03). Girls demonstrated lower FEF50 than boys (z scores: - 2.42 +/- 1.91 vs - 1.56 +/- 1.23; p < 0.001). Clinical parameters evaluated were not found to influence spirometric indices. CONCLUSIONS: Spirometry elicited by CF patients in early childhood can serve as an important noninvasive tool for monitoring pulmonary status. FEV0.5 and flow-related volumes might be more sensitive than the traditional FEV1 in detecting and portraying changes in lung function during early childhood.     

Exercise challenge test in 3- to 6-year-old asthmatic children

RATIONALE: The exercise challenge test (ECT) is a common tool to assess exercise-induced asthma (EIA) in school-aged children. EIA has not been explored in the early childhood setting. OBJECTIVE: To assess the existence of EIA in children in this age group. MEASUREMENTS AND MAIN RESULTS: A 6-min, controlled, free-run test was performed in 55 children (age range, 3 to 6 years old) who were classified into the following groups: 30 children in whom asthma had been previously diagnosed (group A); and 25 children with prolonged coughing (group B). Spirometry measurements were obtained before the run, and at 1, 2, 3, 5, 10, and 20 min after the run. A positive finding of EIA was defined as a 13% decrease from baseline FEV(1) or baseline forced expiratory volume in the first 0.5 s (FEV(0.5)). The actual duration of each run was age-related (mean [+/- SD] duration, 4.8 +/- 0.8 min). The nadir in indexes occurred after a mean time of 2.98 +/- 1.31 min. A positive EIA finding determined by FEV(1) was present in 15 children, and by FEV(0.5) in 34 children. Twenty-six children were from group A, but only 8 children were from group B. Wheezing and/or prolonged expiration were associated with a positive test result in 31 of 34 children. Coughing was frequent in children with both negative and positive ECT findings. CONCLUSION: The present study documents for the first time the presence of EIA in response to a free-run test in early childhood. Our findings suggest that a free-run test for the presence of EIA is suitable, but that the running duration is limited by age. The duration of airflow limitation after exercise is significantly earlier and shorter in young children with asthma compared with older children. FEV(0.5) is a better index than the traditional FEV(1) for describing positive ECT results in young children. The association of wheezing and/or prolonged expiration may help in defining EIA in early childhood in the absence of a spirometer.     

Spirometry and chest roentgenographic appearance in adults with cystic fibrosis.

The pathophysiologic manifestations of cystic fibrosis are continually evolving as more patients survive into their adult years. Although the correlation between chest roentgenographic appearance and pulmonary function testing is well described in children with cystic fibrosis, to our knowledge, there are no data that evaluate this relationship in adults. We analyzed 66 paired studies of chest roentgenographic appearance (Brasfield score) and spirometry in 27 adults with cystic fibrosis between the ages of 18 and 40 years. There was a very good correlation between spirometry and the Brasfield score in adults with cystic fibrosis. The strongest correlation was between the percent predicted FEV1 and the Brasfield score (r = 0.68, p less than 0.001). These correlations were found to remain significant in the patients in whom longitudinal data were available. The FEV1 declined 104 +/- 26 ml/yr in 11 patients who were followed up for a mean duration of 5.8 +/- 0.5 years. The decline in FEV1 per year in adults with cystic fibrosis was significantly greater than in nonsmoking or smoking adults of similar age.     

Thrombophilia in children with cystic fibrosis

In some children with cystic fibrosis (CF), percutaneous long lines occlude sooner than expected (due to thrombophlebitis or thrombosis), and many have a totally implantable venous access device (TIVAD), a recognized complication of which is thrombosis. This complication is more likely if the child has an underlying thrombotic tendency, which may be enhanced in the presence of inflammatory lung disease. There are no reports of an identified association of heritable thrombophilia with CF, although individual cases have been recognized. Our aim was to determine the incidence of thrombophilia in children with CF. In a tertiary pediatric CF center, blood was screened for thrombophilia at annual review, and retested if abnormal. A thrombotic abnormality was found in 41/204 (20%) patients. These included activated protein C resistance (10/204, 5%) with a prevalence similar to that expected, but the following abnormalities had an increased prevalence: antithrombin deficiency (2/204, 1%), protein S deficiency (11/204, 5%), protein C deficiency (8/204, 4%), and lupus anticoagulant (18/204, 9%). There were no differences found in those with thrombophilia for the following parameters: age, gender, genotype, lung function, presence of Pseudomonas aeruginosa, prothrombin time, serum IgE, aspergillus-specific IgE, liver function, and blood inflammatory markers. Fifteen children had TIVADs, 4 of whom had evidence of thrombophilia. In conclusion, a significant proportion of patients had a thrombophilic abnormality. We recommend that thrombophilia screening be performed prior to insertion of a TIVAD, and also in those with a history of venous thrombosis, blocked TIVADs, or recurring problems with long lines.     

Spirometry in an unselected group of 6-year-old children: the DARC birth cohort study

This study presents reference equations for spirometric parameters in 6-year-old children and evaluates the ability of spirometry to discriminate healthy children from children with asthma. Baseline spirometry and respiratory symptoms were assessed in 404 children participating in a longitudinal birth cohort study. Children with known asthma, possible asthma and a control group also performed bronchodilator measurements. At least two acceptable flow-volume curves at baseline were obtained by 368/404 children (91%). The two best values for FEV1 and FVC were within 5% of each other in 88% and 83% of children, respectively. Linear regression analyses for 242 children included in the reference population demonstrated height to be the main predictor of all spirometric indices except FEV1/FVC. FEV1, FEV75, and FVC correlated reasonably to anthropometric data in contrast to flow parameters. Gender differences were found for FEV1, FVC, and FEV75, but not for flow parameters. Asthma was diagnosed in 25/404 children. Baseline lung function in healthy children and children with asthma overlapped, although asthmatic children could be discriminated to some extent. Bronchodilator tests showed a difference in Delta FEV1(mean) between healthy children and children with asthma (3.1% vs. 6.1%, P < 0.05). At a cut-off point of Delta FEV1 = 7.8%, bronchodilator tests had a sensitivity of 46% and a specificity of 92% for current asthma. Spirometry including bronchodilator measurements was demonstrated to be feasible in 6-year-old children and reference values were determined. Spirometry aids the diagnosis of asthma in young children, but knowledge on sensitivity and specificity of these measurements is a prerequisite.     

Bronchial challenge with carbachol in 3-6-year-old children: body plethysmography assessments

Several studies of airway responsiveness in young children (3-6 years old) have been reported, but few have attempted measurements of airway resistance by body plethysmography. Therefore, we decided to study nonspecific bronchial responsiveness following cumulative doses of inhaled carbachol in 44 children with clinical asthma (CA group), 44 children with chronic cough (CC group), 38 children with wheezy bronchitis in the first 2 years of life (WB group), and 40 controls. Specific airway resistance (sRaw) was measured in a body plethysmograph, and specific airway conductance (sGaw=1/sRaw) was calculated. Two parameters were used to assess individual bronchial responses: 1) PD100 (the dose of carbachol which induced a 100% increase in sRaw), and 2) bronchial reactivity (BR), i.e., the slope of the log-dose sGaw response to carbachol. Significant differences were observed in PD100 and BR between the control group and the three groups of young patients (P < 0.001). Moreover, PD100 of the CA group was significantly lower than in the CC group (83.1 +/- 7.8 microg vs. 108.0 +/- 10.2 microg, respectively, P < 0.05), but was similar to the WB group PD100 (94.4 +/- 8.5 microg). BR in the CA group was significantly higher than in both the CC and WB groups (0.127 +/- 0.009 cm H2O-L.sec(-1) x log microg(-1) vs. 0.073 +/- 0.006 cm H2O(-1) x sec(-1) x log microg(-1) and 0.082 +/- 0.006 cm H2O(-1) x sec(-1) x log microg(-1), respectively, P < 0.001). Repeatability and coefficients of variation were always acceptable. Continuous SaO2 monitoring in some children of the CA group demonstrated the safety of the method, which is proposed as a technique in future studies.     

Pulmonary infections in children with cystic fibrosis

Bronchopulmonary infections continue to be the major determinant of morbidity and mortality in patients with cystic fibrosis (CF). The basic pathogenesis of disease includes abnormal secretions and impaired mucociliary clearance. Colonization of the tracheobronchial tract with bacteria is then associated with a cycle of infection, inflammation and airway obstruction eventually leading to respiratory insufficiency. Early clinical features include persistent cough and failure to thrive. Hyperinflation and bronchial thickening are early radiographic changes suggestive of CF. Staphylococcus aureus is commonly the initial respiratory pathogen. Subsequently, Hemophilus influenzae and Pseudomonas aeruginosa colonize the respiratory tract. In addition, respiratory viruses and other pathogens such as Legionella and mycoplasma are implicated in the etiology of pulmonary infections. The culture of respiratory secretions such as sputum are important guidelines to the etiology of pulmonary infection in CF. The laboratory must be aware of the pathogens that are typical of this disease and use appropriate techniques and media. In large part, advances in treatment in CF over the past two decades are due to the availability of increasingly potent antibiotic agents. However, effective treatment must be multifaceted and include a variety of nonantimicrobial therapies. Different approaches to the antibiotic therapy of pulmonary infection in CF, including prevention, suppression, and definitive treatment are discussed. In addition to traditional antibiotic therapy, a variety of newer methods of therapy in CF are discussed. These include oral antipseudomonal antibiotics, corticosteroid therapy, aerosolized antibiotics, and continuous antimicrobial prophylaxis.     

Antibody response to Pseudomonas aeruginosa in children with cystic fibrosis

Cystic fibrosis (CF) is the most frequent life threatening autosomal recessive disease in white subjects. The primary cause of morbidity and mortality in children with CF is chronic pulmonary infection, mainly caused by Pseudomonas aeruginosa. The purpose of this study was to assess the value of the measurement of antibodies to P. aeruginosa in diagnosing lung infection by the bacteria in CF patients. We assessed P. aeruginosa antibody titers in CF patients from Rio de Janeiro, Brazil, using cell lysate antigens as well as recombinant PcrV, a Type III Secretion System protein. Sputum (more than 70% of the specimens) or oropharyngeal swabs were obtained whenever patients were regularly followed for their pulmonary disease. Blood samples were obtained with an average interval of 6 months for a period of 2 years. The ELISA cut‐offs were assigned as the positive 95% confidence interval of the mean antibody levels from non‐fibrocystic controls. Our data showed that most CF patients (81%) of whom were not chronically infected by P. aeruginosa (Groups I and II), had their first serology positive for rPcrV. Cell‐lysate ELISA was able to detect P. aeruginosa antibodies before positive culture in the first serum sample of 44% of the patients from Groups I and II. When serum reactivity to rPcrV and cell lysate were combined, 94% of CF patients from Groups I and II (n = 16) had the first serology positive for P. aeruginosa over a mean time of 20 months before the first isolation of P. aeruginosa. In conclusion, longitudinal P. aeruginosa serology should become part of respiratory care follow‐up, in conjunction with other lung parameter functions. Pediatr Pulmonol. 2009; 44:392–401. © 2009 Wiley‐Liss, Inc.     

Bronchial response to nebulized antibiotics in children with cystic fibrosis

Nebulized antibiotics are being used increasingly in children with cystic fibrosis. We assessed the effect of nebulized antibiotic solutions of varying tonicity on lung function in 12 children aged 5-15 yrs with cystic fibrosis. Baseline forced expiratory volume in one second and (FEV1) was measured, followed by a single nebulization of normal saline (272 mosmol.kg-1), tobramycin (248 mosmol.kg-1), or ticarcillin (3,080 mosmol.kg-1). All children received each of these, administered randomly, one per day. FEV1 was remeasured 5, 15 and 30 min after completion of the nebulization. Ticarcillin (mean fall 10.7% (SD 8.9)) caused a larger fall in FEV1 than normal saline (4.8% (4.3), p less than 0.05). The fall in FEV1 for ticarcillin was greater than for tobramycin (1.2% (2.0), p less than 0.05). Normal saline did not result in a significantly larger fall in FEV1 than tobramycin (p greater than 0.05). Bronchoconstriction to ticarcillin persisted at 30 min. We conclude that nebulized antibiotics can affect lung function in children with cystic fibrosis if the solutions are hypertonic.     

Spirometric pulmonary function in 3- to 5-year-old children

Forced expiratory maneuvers are routinely used in children, 6 years of age and older for the diagnosis and follow-up of respiratory diseases. Our objective was to establish normative data for an extensive number of parameters measured during forced spirometry in healthy 3- to 5-year-old children. Children aged between 3 and 5 years were tested in 11 daycare centers. Usual parameters, including FEV1, FVC, PEF, FEF(25-75), FEF25, FEF50, FEF75, and Aex were measured and analyzed in relation to sex, age, height, and weight. In addition, the same analysis was performed for FEV0.5 and FEV0.75. One hundred sixty-four children were recruited for testing including 87 girls and 77 boys. Thirty-five were 3 years old, 63 were 4 years old, and 66 were 5 years old. Overall, 143 children (87%) accepted to perform the test and 128 children (78%) were able to perform at least two technically acceptable expiratory maneuvers. Analyses using different regression models showed that height was the best predictor for every parameter. In conclusion, the present study confirms that most healthy 3-5 years old children can perform valid forced expiratory maneuvers. In agreement with other studies, we found that height is the most important single predictor of various parameters measured on forced spirometry. The present study is the first to establish normative values for FEV0.75, as well as to demonstrate that Aex can be easily performed in the majority of children aged 3-5 years. These are likely important parameters of lung function in this age range.     

A 56-year-old man with cystic fibrosis and coeliac disease

Although it has been reported that cystic fibrosis and coeliac disease can coexist, a clear relationship between the two diseases has never been firmly established. Our case concerns a 56-year-old man with cystic fibrosis (delta F508/N1303J). Over the last two years he had been complaining about diarrhoea and meteorism. The serum level of tissue transglutaminase was elevated. Duodenoscopy showed a typical pattern for coeliac disease. This was confirmed by the biopsy. After three months on a gluten-free diet the symptoms had disappeared. In the literature there are some hypotheses to explain the coexistence of cystic fibrosis and coeliac disease. Due to pancreatic insufficiency in patients with cystic fibrosis the mucosa of the bowel may have more contact with the complete gluten protein. In addition, malnutrition might contribute to some additional mucosal damage. Both mechanisms might induce an inappropriate immune response to dietary gluten. In the literature all cystic fibrosis patients with coeliac disease were diagnosed with both diseases in childhood with a maximum latency between both diseases of 26 months. It seems unlikely that manifest coeliac disease remained undiagnosed in our patient since childhood. The long time gap between the diagnosis of cystic fibrosis and the first symptoms of the celiac disease in our patient could support the above-mentioned pathophysiological hypotheses.     

Palivizumab immunoprophylaxis effectiveness in children with cystic fibrosis

Background

Evidence on the effectiveness of respiratory syncytial virus (RSV) immunoprophylaxis with palivizumab in children with cystic fibrosis (CF) is lacking.

Methods

We utilized Medicaid Extract files from 27 states from 1999 to 2006 linked to the National Cystic Fibrosis Registry to establish a cohort of children 0–2 years with CF diagnosis. Eligible children entered the cohort after CF diagnosis and after RSV season onset, and were followed until season end, second birthday, death, or hospitalizations for reasons other then the study outcome. Two outcomes were examined: hospitalization for RSV infections (RSV‐ha), or hospitalization for acute respiratory infections (ARI‐ha). Palivizumab exposure was defined based on pharmacy or procedure claims as current (claim date plus 30 days), former (day 31–60 after a claim), and no exposure (days before the first or >60 days after any claim). Both outcomes were examined in a Cox regression model, adjusting for RSV risk factors and CF severity via exposure propensity score.

Results

The matched cohort included 1,974 infants (2,875 infant seasons), who experienced 32 RSV‐ha and 212 ARI‐ha (3.9 and 26.2/1,000 season months, respectively). Compared to periods of no use, the adjusted hazard ratio for current use was 0.57 (95% confidence interval [CI]: 0.20–1.60) for RSV‐related hospitalization and 0.85 (95% CI: 0.59–1.21) for ARI‐related hospitalization. Each month of increasing age reduced the ARI‐ha by 5.8%.

Conclusion

RSV hospitalization incidence was low suggesting either little contribution of the virus to respiratory infections in patients with CF or lack of RSV testing. Unadjusted and adjusted RSV‐hospitalization incidence rates suggested potentially positive effects of palivizumab, but results were inconclusive due to small event rates. Hospitalizations for acute respiratory illness with possible RSV contribution showed no association with palivizumab use, suggesting limited overall effect of palivizumab. Younger age greatly increased infection risk. Pediatr Pulmonol. 2013; 48:874–884. © 2012 Wiley Periodicals, Inc.

     

Preserved diffusion capacity in children with cystic fibrosis

Early detection of progressive lung disease in cystic fibrosis (CF) may lead to better treatment and prognosis. Routine lung function indices may be relatively insensitive markers of peripheral airway obstruction and alveolar collapse. We hypothesized that the single-breath diffusion capacity of the lung for carbon monoxide (DLCO) would change before tests of airway function in patients with CF. We assessed lung function longitudinally in 53 children with CF during a mean period of 3.8 years to determine whether the diffusion capacity of the lung becomes abnormal before more conventional indices of lung function do. Within patients, DLCO was slightly elevated and remained stable, while forced expired volume in 1 sec (FEV1) and forced vital capacity (FVC) declined progressively (mean individual decline, -1.8% and -0.8% of predicted). Cross-sectionally, this decline was faster (mean group decline -3.8% and -2.8% of predicted), indicating an additional cohort effect. Normalized diffusion capacity at an early stage of CF is slightly elevated and is preserved in spite of progressive obstructive lung disease. This can be attributed to alterations in pulmonary and bronchial circulation due to loss of function and/or number of alveolar units. Diffusion capacity at rest does not appear to be a suitable early marker of progressive deterioration of CF lung disease.     

Respiratory inductance plethysmography in healthy 3- to 5-year-old children

STUDY OBJECTIVES: Because of the challenges of using standard measurements such as spirometry to measure respiratory function in 3- to 5-year-old children, there may be a role for respiratory inductive plethysmography (RIP), which is noninvasive and requires minimal subject cooperation. In this study, we described normative values of thoracoabdominal motion and timing mechanics in 3- to 5-year-old children, and hypothesized positional dependence of these measurements in this age group. DESIGN: We measured relative thoracoabdominal motion during tidal breathing using the phase angle (Phi), the labored breathing index, and the phase relation during the total breath and timing mechanics with the ratio of time to peak tidal expiratory flow to expiratory time (TPTEF/TE). SETTING: Preschools within the greater Philadelphia area and the Pulmonary Office of The Children's Hospital of Philadelphia. PATIENTS OR PARTICIPANTS: Fifty healthy children between 3 years and 5 years of age. INTERVENTIONS: RIP. MEASUREMENTS AND RESULTS: All measures varied with position. Thoracoabdominal motion was nearly synchronous in the sitting position and most asynchronous in the supine position (Phi, 15.7 +/- 4.0 degrees vs 56.1 +/- 4.3 degrees, respectively; p < 0.001). This also led to an increase in the TPTEF/TE from the sitting to the supine positions (30.3 +/- 1.4% vs 37.0 +/- 1.6%, respectively; p < 0.001). Measurements of thoracoabdominal motion and timing mechanics did not change with age, weight, height, or gender. CONCLUSIONS: We conclude that the positional dependence of these measurements is due to the alteration in respiratory mechanics between the sitting, standing, and supine positions. We further conclude that if RIP is to be a useful longitudinal measure of respiratory function in this age range, comparison measurements should be made in the same position.