Chest ACCP Member Benefits
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Guest Access | Sign In via User Name/Password
doi:10.1378/chest.06-1351
(Chest. 2007; 131:356-361)
© 2007 American College of Chest Physicians
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Article Archive
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via ISI Web of Science (1)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Vilozni, D.
Right arrow Articles by Augarten, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Vilozni, D.
Right arrow Articles by Augarten, A.

Spirometry in Early Childhood in Cystic Fibrosis Patients*

Daphna Vilozni, PhD; Lea Bentur, MD; Ori Efrati, MD; Tal Minuskin, MD; Asher Barak, MD; Amir Szeinberg, MD; Hannah Blau, MD; Elie Picard, MD; Eitan Kerem, MD; Yaacov Yahav, MD and Arie Augarten, MD

* From The Edmond and Lili Safra Children’s Hospital (Drs. Vilozni, Efrati, Minuskin, Barak, Szeinberg, Yahav, and Augarten), Sheba Medical Center, Ramat-Gan; Meyer Children’s Hospital (Dr. Bentur), Rambam Medical Center, Haifa; Schneider Children’s Medical Center (Dr. Blau), Petach-Tikva; Shaare Zedek Medical Center (Dr. Picard), Jerusalem; and Hadassah Medical Center (Dr. Kerem), Mount Scopus, Jerusalem, Israel.

Correspondence to: Daphna Vilozni, PhD, Pediatric Pulmonary Unit, The Edmond and Lily Safra Children’s Hospital, Chaim Sheba Medical Center, Tel HaShomer, Ramat-Gan, Israel, 52621; e-mail: avi_vil{at}bezeqint.net

Abstract

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.

Key Words: airflow obstruction • cystic fibrosis • early childhood • prognosis • pulmonary infection • spirometry

Pulmonary infection and inflammation play a key role in the course and prognosis of patients with cystic fibrosis (CF).1 There is evidence that these harmful processes start early, even in very young, asymptomatic children. Therefore, early identification and aggressive intervention is essential. Some centers currently use BAL and high-resolution CT methods for monitoring airway inflammation and infection. However, the former is invasive while the latter involves radiation and therefore cannot be performed routinely.

Spirometry is the most important measure of pulmonary status in individuals with CF.234 There are plenty of data regarding spirometry patterns in CF school-age children and adults.56 Spirometry performed by the raised-volume, rapid thoracoabdominal compression technique has shown that at diagnosis, CF infants may already have evidence of airflow obstruction.789

Performance of spirometry has been considered technically problematic in early childhood. Studies10111213 have indicated that healthy young children are capable of producing reliable spirometry maneuvers that are comparable in quality to studies of older children. Several studies131415 used spirometry in a limited number of early childhood CF patients. These studies were inconclusive regarding the ability of the spirometry to detect airway obstruction in this age group, and there were no findings concerning the emergence of obstructed lung function in relation to age. Other lung function methods, which require minimal active cooperation, have been suggested as appropriate in this age group, and include Helium dilution functional residual capacity measurements,14 and resistance of the respiratory system by the interrupter technique.16 The ability of these methods to reveal abnormal lung function was inconsistent. Specific resistance of the airway (sRaw) measured by whole-body plethysmography has also been evaluated, with levels found to be higher than healthy in nearly half of the CF children.17 Multiple in-breath washout14 has shown an increased lung clearance index in a high percentage of preschool CF children. The two latter techniques are fairly sophisticated. The aims of this study were to enhance objective information on lung function by measuring spirometry in a large number of early childhood CF patients, and to evaluate the utility of spirometry in detecting early airways obstruction.

Materials and Methods

The study was a cross-sectional, multicenter, single-occasion, observational study. Children with CF (age range, 2.5 to 6.9 years) were recruited from five CF centers in Israel. The children were included if they were clinically stable as determined by clinical criteria, and had no acute exacerbation of respiratory symptoms for the prior 3 weeks. The following parameters were derived from medical charts: genetic profile, the presence of Pseudomonas in the sputum or oropharyngeal cultures in some patients who were unable to provide sputum, and pancreas status (sufficient or insufficient). Parental consent for the child’s spirometry performance was given before entering the study. The Helsinki Boards approved the study.

Children were defined as having severe genotype when they carried two of the following CF mutations: {Delta}F508, W1282X, G542X, N1303K, S549R, previously found to be associated with a severe disease presentation (ie, high levels of sweat chloride and pancreatic insufficiency).18 Mild genotype included compound heterozygote patients who carried one CF mutation known to cause mild disease (ie, borderline or normal sweat test and pancreatic sufficiency): 3849 + 10 kb C -> T, 5T, G85E.1920

Spirometry was performed in the Pediatric Pulmonary Function Laboratory at each center. Spirometry is a routine part of the clinical assessment from the day the child can perform the test. A single investigator (D.V.), who visited the different centers, was responsible for all tests performed, using the same spirometer. Spirometry was measured with a commercial, portable spirometer (ZAN100; ZAN Messgeraete GmbH; Oberthulba, Germany). Calibration was performed before each testing session. The spirometer software included on-line analysis of the forced expiratory flow volume curves. The curves were monitored on the computer screen to ensure best effort. Results were corrected to body temperature and pressure, saturated.

A parent was present during the test. The children were asked to refrain from using bronchodilators 12 h prior to the test. Tests were performed in a standing position. Each child was given a filter, and the whole breathing apparatus was disinfected between the subjects. Nose clips were not used because they were uncomfortable to the child, leading to less cooperation and refusal to perform the test. The method of spirometry was taught with the aid of interactive respiratory games (SpiroGame; patented by Dr. Vilzone, 2003) corresponding to the forced spirometry maneuver.10 Maneuvers were repeated to obtain best possible efforts on at least three visually, technically acceptable curves. Sessions lasted up to 15 min per child but were shorter if three repetitive, technically acceptable curves were achieved. The best two of the three curves with the maximal FVC plus FEV1 (or FVC plus forced expiratory volume in 0.5 s [FEV0.5]) were analyzed for the study.

Analysis of Spirometry
The investigator and the physician at each center inspected the curves for technical errors. The two best curves had to meet most American Thoracic Society/European Respiratory Society criteria2122 (for start of test, end of test, and reproducibility) and preschool spirometry criteria.1113 Expiratory time < 1 s (but > 0.5 s) was accepted if the other criteria were met. The following indices were obtained: FVC, FEV0.5, FEV0.5/FVC ratio, FEV1, FEV1/FVC ratio, peak expiratory flow rate (PEFR), forced expiratory flow at 25 to 75% of vital capacity (FEF25–75), and forced expiratory flow at 50% of vital capacity (FEF50); values were compared to those derived from the aforementioned indices in 109 healthy children in our prior study11 with relation to height. Values were further calculated as a z score from healthy (a z score is the number of SDs that a value deviates from the expected mean of healthy). Lung functions were defined as "abnormal" when the z score was more negative than – 2.0 SDs. In addition, spirometry indices were analyzed with relation to age group as follows: age 3 (2.5 to 3.9 years old); age 4 (4.0 to 4.9 years olds); age 5 (5.0 to 5.9 years old); and age 6 (6.0 to 6.9 years old). The effects of CF genotype, gender, Pseudomonas colonization, and pancreatic status on pulmonary function were also evaluated.

Statistical Analysis
Statistical analysis was performed using paired t tests in relation to healthy control subjects or unpaired t tests with respect to the study groups. Correlations of each parameter with age were calculated by regression analysis. A p value < 0.05 was considered statistically significant.

Results

Ninety-three children with CF were enrolled in the study. Seventy-six of the 93 children (29 girls and 47 boys) were able to perform at least three visually, technically acceptable forced expiratory flow volume curves according to previous studies.1012 In seven children, expiration was < 1 s but longer than FEV0.5; otherwise, curves were technically acceptable. The numbers of children in each age group were as follows: age 3, n = 17; age 4, n = 16; age 5, n = 20; and age 6, n = 23. The median age was 5.1 years (range, 2.5 to 6.9 years), median height was 107 m (range, 83 to 124 m), median weight was 17 kg (range, 10 to 23 kg), and the median body mass index was 15.1 kg/m2 (range, 12.0 to 18.1 kg/m2).

Examples of normal and obstructed forced expiratory flow volume curves are presented in Figure 1 . The curves are related to those of our reference group.10 Spirometry values for the entire population presented as z scores (mean ± SD) from healthy control subjects are displayed in Figure 2 . Baseline spirometry indices are presented in Table 1 in relation to healthy control subjects. Abnormal z score values of FVC, FEV1, and PEFR were found in very few patients (0, 7, and 6 patients, respectively), while abnormal z score values of FEV0.5, FEF25–75, and FEF50 were found more frequently (14, 29, and 34 patients, respectively). Spirometry indices in relation to age groups are presented as a z score from healthy in Figure 3 and in Table 2 .


Figure 1
View larger version (17K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 1. Two patterns of flow volume curves. Top: Normal flow volume curve. Bottom: Obstructed flow volume curve. ref = reference.

 

Figure 2
View larger version (17K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 2. Spirometry values for the entire CF group compared with our healthy control subject (subject 11).

 

View this table:
[in this window]
[in a new window]

  		Table 1. Baseline Spirometry Indices Presented as z Score From Healthy*

 

Figure 3
View larger version (14K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 3. Changes of z score from healthy in spirometry indices according to the age range studied.

 

View this table:
[in this window]
[in a new window]

  		Table 2. Individual Parameters in z Score From Healthy in Relation to Age Group*

 
FVC and FEV1 did not change significantly over the age range studied. The emergence of an abnormal z score at 6 years for FEV0.5, PEFR, FEF25–75, and FEF50 parameters was high (in 11 children, 47.8%; 5 children, 21.7%; 15 children, 65.2%; and 19 children, 82.7%, respectively). The proportion of 6-year-old children having FEF25–75 values more negative than 2 SDs was significantly higher than in 3-year-old children (65% vs 5%, respectively; p < 0.03). Detailed information for FEV0.5 vs FEV1 with respect to age, based on the individual results, is presented in Figure 4 .


Figure 4
View larger version (27K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 4. Effect on age on FEV1 and FEV0.5. Dots represent individual data. The solid line is the best exponential fit for the CF children. The dashed line is the reference line for healthy children.

 
Girls presented with lower flow-related volumes than boys: z scores of – 2.62 ± 2.07 vs – 1.50 ± 1.50 for FEF25–75, and – 2.42 ± 1.91 vs – 1.56 ± 1.23 for FEF50, respectively. Both parameters were significantly lower than the healthy population (p < 0.02).

We found no differences in the spirometry indices between children whose sputum yielded Pseudomonas (n = 35) and those who did not (n = 41). Similarly, no difference was found between children with pancreatic sufficiency (n = 18) or insufficiency (n = 58). Further analysis showed that spirometry indices did not differ between children with both Pseudomonas colonization and pancreatic insufficiency (n = 28) to those without Pseudomonas who were pancreatic sufficient (n = 12). No differences were found in spirometry indices between patients carrying two severe mutations (n = 54) and those carrying a mild mutation (n = 12).

Discussion

This is the largest study evaluating and quantifying lung function by spirometry in CF patients during early childhood. Our patients demonstrated lower flows than comparable healthy children. Deviations from healthy were more prominent in the 6-year-old group. FEV0.5 and flow-related volumes were found to be more sensitive than the traditional FEV1 for detecting and portraying changes in lung function in early childhood.

Early detection and early aggressive intervention are of paramount importance in preventing pulmonary deterioration. Early childhood represents a critical time span during which the disease may progress asymptomatically. The purposes of this study were to provide quantifiable information derived from spirometry in young CF children, and to evaluate its usefulness in detecting airways obstruction. Prior studies131415 did not deal with regression of lung function with age in these young children.

Quality control of the spirometry met criteria suitable for this age group,1113 and the success rate in performing technically correct spirometry in our CF population (81.7%) was similar to success rates for young CF children reported previously (89.6% and 77.5%).1415 The significance of each spirometry index in revealing abnormal lung function is discussed.

FVC values in our group were significantly lower than in the healthy population, but none were abnormal. Our FVC z score values were close to those found by Aurora et al.14 Compared with school age, there was a similar trend to those described previously in children between the ages of 6 and 12 years.23 Similarly to FVC, PEFR z scores values were significantly lower than in healthy younger population, and even at age 6 years only a few children had abnormal values.

Among the spirometry indices, FEV1 in school children and adults was found to be directly related to airways obstruction, morbidity, and mortality in CF patients.24 FEV1 in our group was also significantly lower than in the healthy population, but only a few children presented with abnormal z score values. This could be explained by approximately 95% of FVC being emptied in 1 s. Although a higher percentage of children presented with abnormal FEV1,15 the findings were attributed to inability to forcefully exhale for 1 s, and not to genuine, lower-than-healthy values. The emergence of abnormal FEV1 in our 6-year-old children was similar in magnitude to FEV1 presented when children were > 6 years old.23

In contrast to the previous parameters, the FEV0.5 z score was already abnormal in 34% of our children at the age of 3 years. In that respect, abnormal FEV0.5 was found even in 30% of asymptomatic CF infants.25 At age 6 years, 52% of the children had abnormal FEV0.5 values. The appearance of abnormal FEV0.5 in our population was similar to previously reported, higher-than-healthy sRaw (measured within the plethysmograph).14 It is therefore suggested that FEV0.5 is better than FEV1 as a predictor of abnormal lung function.

Abnormal z score levels of FEF50 and FEF25–75 were detected in 38.2 to 44.7% of the population, respectively. Age-related, abnormal FEF50 rates in our 3-year-olds were lower than previously reported by Ranganathen et al25 for infants. By 6 years of age, 65.2% had low FEF25–75 values and 82.6% had low FEF50 values. The emergence of abnormal z scores of flow-related volumes were consistent with those measured in 6- to 12-year-old CF children.23 These indices previously have been shown to be the first to deteriorate in asthmatic children.26 But the large SD of these indices, and their dependency on actual FVC, makes their use as predictors for worsening of lung function debatable. Aurora et al14 have shown that only 13% or 14% of the studied population had low FEF25–75 values. They suggested that fatigue toward end-expiration causing low FVC values may artificially lead to elevation of the flow-related volume parameters. In relation to other methods, the rate of children with abnormal flow-related volume in our study is comparable with the high sRaw and lung clearance index found by others.1417 Interestingly, girls presented with reduced flow-related volume parameters compared with boys. This pattern was previously described in adult CF patients, in whom women demonstrated accelerated deterioration in pulmonary function.27

Marostica et al15 were able to associate lower lung function with homozygous {Delta}F508 mutations. We found no differences in any of the measured parameters between patients who carry two mutations in one allele. Our results were similar to findings in adults28 and in infants,25 showing no correlation between genotype and lung function. Lack of correlation between lung function results and genotype may relate to the small number of patients in our group.

Studies293031 have shown that lower respiratory tract bacterial infections and inflammation are closely related to abnormal pulmonary function. The fact that no difference in pulmonary function was found in our study between children whose lungs were colonized with Pseudomonas and those with negative sputum culture results lends credence to the theory that airway inflammation in CF might precede chronic bacterial colonization. Another possibility is that oropharyngeal cultures, performed in some of the centers that participated in our study, may not detect lower airway colonization.

Limitations
This study involved five centers. However, all Israeli CF centers use the same treatment protocols and share a central computerized database. Additionally, all spirometry tests were performed by a single person using the same spirometer. Therefore, center effect was insignificant. CF is variable and, although this was the largest early childhood group evaluated with spirometry, larger groups should be evaluated in order to draw firm conclusions regarding correlation with clinical parameters.

Conclusions

We found that CF patients in early childhood demonstrate lower flows and flow-related volume parameters compared with the healthy population. FEV0.5 and flow-related volume parameters are sensitive spirometry indices to detect airway obstruction. These parameters were found to be better than the traditional FEV1 in predicting abnormal lung function in this age group. We suggest that spirometry can serve as a noninvasive tool for evaluating lung function. Larger, prospective studies evaluating each CF patient longitudinally should be performed.

Footnotes

Abbreviations: CF = cystic fibrosis; FEF25–75 = forced expiratory flow at 25 to 75% of vital capacity; FEF50 = forced expiratory flow at 50% of vital capacity; FEV0.5 = forced expiratory volume in 0.5 s; PEFR = peak expiratory flow rate; sRaw = specific resistance of the airway

This study was funded by the Israel Lung Association, Tel-Aviv, Israel.

The authors have no conflicts of interest to disclose.

Received for publication June 27, 2006. Accepted for publication August 31, 2006.

References

  1. Davis, PB, Drumm, M, Konstan, MW (1996) Cystic fibrosis: state of the art. Am J Respir Crit Care Med 154,1229-1256[ISI][Medline]
  2. Corey, M, Edwards, L, Levison, H, et al Longitudinal analysis of pulmonary function decline in patients with cystic fibrosis. J Pediatr 1997;131,809-814[CrossRef][ISI][Medline]
  3. Farrell, PM, Li, Z, Kosorok, MR, et al Bronchopulmonary disease in children with cystic fibrosis after early or delayed diagnosis. Am J Respir Crit Care Med 2003;168,1100-1108[Abstract/Free Full Text]
  4. Wall, MA, LaGesse, PC, Istvan, JA The "worth" of routine spirometry in a cystic fibrosis clinic. Pediatr Pulmonol 1998;25,231-237[CrossRef][ISI][Medline]
  5. Kerem, E, Reisman, J, Corey, M, et al Prediction of mortality in patients with cystic fibrosis. N Engl J Med 1992;326,1187-1191[Abstract]
  6. Milner, AD Lung volume measurements in childhood. Paediatr Respir Rev 2000;1,135-140[Medline]
  7. Tepper, RS Assessment of the respiratory status of infants and toddlers with cystic fibrosis. J Pediatr 1998;132,380-381[CrossRef][ISI][Medline]
  8. Gappa, M, Ranganathan, SC, Stocks, J Lung function testing in infants with cystic fibrosis: lessons from the past and future directions. Pediatr Pulmonol 2001;32,228-245[CrossRef][ISI][Medline]
  9. Ranganathan, SC, Stocks, J, Dezateux, C, et al The evolution of airway function in early childhood following clinical diagnosis of cystic fibrosis. Am J Respir Crit Care Med 2004;169,928-933[Abstract/Free Full Text]
  10. Vilozni, D, Barker, M, Jellouschek, H, et al An interactive computer-animated system (SpiroGame) facilitates spirometry in preschool children. Am J Respir Crit Care Med 2001;164,2200-2205[Abstract/Free Full Text]
  11. Vilozni, D, Barak, A, Efrati, O, et al The role of computer games in measuring spirometry in healthy and "asthmatic" preschool children. Chest 2005;128,1146-1155
  12. Eigen, H, Bieler, H, Grant, D, et al Spirometric pulmonary function in healthy preschool children. Am J Respir Crit Care Med 2001;163,619-623[Abstract/Free Full Text]
  13. Aurora, P, Stocks, J, Oliver, C, et al Quality control for spirometry in preschool children with and without lung disease. Am J Respir Crit Care Med 2004;169,1152-1159[Abstract/Free Full Text]
  14. Aurora, P, Gustafsson, P, Bush, A, et al Multiple breath inert gas washout as a measure of ventilation distribution in children with cystic fibrosis. Thorax 2004;59,1068-1073[Abstract/Free Full Text]
  15. Marostica, PJ, Weist, AD, Eigen, H, et al Spirometry in 3- to 6-year-old children with cystic fibrosis. Am J Respir Crit Care Med 2002;166,67-71[Abstract/Free Full Text]
  16. Beydon, N, Amsallem, F, Bellet, M, et al Pulmonary function tests in preschool children with cystic fibrosis. Am J Respir Crit Care Med 2002;166,1099-1104[Abstract/Free Full Text]
  17. Nielsen, KG, Pressler, T, Klug, B, et al Serial lung function and responsiveness in cystic fibrosis during early childhood. Am J Respir Crit Care Med 2004;169,1209-1216[Abstract/Free Full Text]
  18. The Cystic Fibrosis Genotype-Phenotype Consortium.. Correlation between genotype and phenotype in patients with cystic fibrosis. N Engl J Med 1993;329,1308-1313[Abstract/Free Full Text]
  19. Augarten, A, Kerem, BS, Yahav, Y, et al Mild cystic fibrosis and normal or borderline sweat test in patients with the 3849 + 10 kb C–>T mutation. Lancet 1993;342,25-26[CrossRef][ISI][Medline]
  20. Chillon, M, Casals, T, Mercier, B, et al Mutations in the cystic fibrosis gene in patients with congenital absence of the vas deferens. N Engl J Med 1995;332,1475-1480[Abstract/Free Full Text]
  21. Standardization of spirometry, 1994 update: statement of the American Thoracic Society. Am J Respir Crit Care Med 1995;153,1107-1236
  22. Quanjer, PH, Tammeling, GJ, Cotes, JE, et al Lung volumes and forced ventilatory flows: report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society. Eur Respir J Suppl 1993;16,5-40[Medline]
  23. Morgan, WJ, Butler, SM, Johnson, CA, et al Epidemiologic study of cystic fibrosis: design and implementation of a prospective, multicenter, observational study of patients with cystic fibrosis in the U.S. and Canada. Pediatr Pulmonol 1999;28,231-241[CrossRef][ISI][Medline]
  24. Belkin, RA, Henig, NR, Singer, LG, et al Risk factors for death of patients with cystic fibrosis awaiting lung transplantation. Am J Respir Crit Care Med 2006;173,659-666[Abstract/Free Full Text]
  25. Ranganathan, SC, Dezateux, C, Bush, A, et al London Collaborative Cystic Fibrosis Group. Airway function in infants newly diagnosed with cystic fibrosis. Lancet 2001;358,1964-1965[CrossRef][ISI][Medline]
  26. Bar-Yishay, E, Amirav, I, Goldberg, S Comparison of maximal midexpiratory flow rate and forced expiratory flow at 50% of vital capacity in children. Chest 2003;123,731-735
  27. Schneiderman-Walker, J, Wilkes, DL, Strug, L, et al Sex differences in habitual physical activity and lung function decline in children with cystic fibrosis. J Pediatr 2005;147,321-326[CrossRef][ISI][Medline]
  28. de Gracia, J, Mata, F, Alvarez, A, et al Genotype-phenotype correlation for pulmonary function in cystic fibrosis. Thorax 2005;60,558-563[Abstract/Free Full Text]
  29. Dakin, CJ, Pereira, JK, Henry, RL, et al Relationship between sputum inflammatory markers, lung function, and lung pathology on high-resolution computed tomography in children with cystic fibrosis. Pediatr Pulmonol 2002;33,475-482[CrossRef][ISI][Medline]
  30. Khan, TZ, Wagener, JS, Bost, T, et al Early pulmonary inflammation in infants with cystic fibrosis. Am J Respir Crit Care Med 1995;151,1075-1082[Abstract]
  31. Rosenfeld, M, Emerson, J, Accurso, F, et al Diagnostic accuracy of oropharyngeal cultures in infants and young children with cystic fibrosis. Pediatr Pulmonol 1999;28,321-328[CrossRef][ISI][Medline]




This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Article Archive
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via ISI Web of Science (1)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Vilozni, D.
Right arrow Articles by Augarten, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Vilozni, D.
Right arrow Articles by Augarten, A.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS