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


     

Guest Access | Sign In via User Name/Password
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 Santamaria, F.
Right arrow Articles by Boner, A. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Santamaria, F.
Right arrow Articles by Boner, A. L.
(Chest. 2006;130:480-486.)
© 2006 American College of Chest Physicians

Lung Structure Abnormalities, But Normal Lung Function in Pediatric Bronchiectasis*

Francesca Santamaria, MD; Silvia Montella, MD; Luigi Camera, MD; Cristiana Palumbo, MD; Luigi Greco, MD and Attilio L. Boner, MD

* From the Departments of Pediatrics (Drs. Santamaria, Montella, and Greco) and Radiology (Drs. Camera and Palumbo), Federico II University, Naples, Italy; and the Department of Pediatrics (Dr. Boner), University of Verona, Verona, Italy.

Correspondence to: Attilio L. Boner, MD, Department of Pediatrics, University of Verona, Piazzale L. Scuro, 37134, Verona, Italy; e-mail: attilio.boner{at}univr.it

Abstract

Background: Bronchiectasis is not considered to be uncommon in children anymore. The relationship between pulmonary function and severity of bronchiectasis is still controversial.

Study objectives: To assess the extent and severity of bronchiectasis through high-resolution CT (HRCT) scan score, and to correlate it with clinical, microbiological, and functional data.

Patients and methods: Forty-three white children with HRCT-diagnosed bronchiectasis were studied. Bronchiectasis extent, bronchial wall thickening severity, and bronchial wall dilatation severity were evaluated using the Reiff score. Clinical, microbiological, and spirometry results were related to total HRCT scan score and to subscores as well.

Results: The percentages of affected lobes were as follows: right lower lobe, 65%; middle lobe, 56%; left lower lobe, 51%; right upper lobe, 37%; lingula, 30%; and left upper lobe, 30% ({chi}2 = 18.4; p = 0.002). The mean (± SEM) HRCT score was 20 ± 2.6. Total score or subscores of bronchiectasis extent, bronchial wall thickening severity, and bronchial wall dilatation severity were not significantly related to FEV1 and FVC. Seventy-four percent of patients had asthma. The age at the onset of cough correlated with age at the time of the HRCT scan (p = 0.004) and with the presence of asthma (p = 0.01). Positive findings of deep throat or sputum cultures were found more frequently in atopic patients (p = 0.02) and asthmatic (p < 0.01) patients, and in children who were < 2 years of age at the onset of cough (p < 0.01).

Conclusions: Normal lung function may coexist with HRCT scan abnormalities and does not exclude damage to the bronchial structure. Pulmonary function is not an accurate method for assessing the severity of lung disease in children with bronchiectasis.

Key Words: bronchiectasis • children • high-resolution CT scan

Since the introduction of high-resolution CT (HRCT) scanning, especially the low-dose HRCT scan that provides good-quality lung images and can be safely obtained in patients at any age,1 bronchiectasis has not been considered uncommon in children,234567891011 even though quantitative estimates of the prevalence of bronchiectasis in children worldwide are lacking.6

The relationship between pulmonary function test (PFT) results and cystic fibrosis (CF) or non-CF bronchiectasis HRCT scan score is still controversial. Some studies91112131415161718 have reported a correlation between the severity of the bronchiectasis HRCT scan score and the reduction in lung function parameters, while others did not819202122 or found only a fair-to-moderate association.23 We designed a study in a group of children with HRCT scan-proven bronchiectasis in which the primary aim was to correlate HRCT scan scores with clinical, microbiological, and PFT findings.

Materials and Methods

Patients
Forty-three white children (22 male children) with bronchiectasis previously identified by HRCT scanning124 were enrolled into the study. They represented all of the subjects with bronchiectatis in the authors’ practice. Recurrent pneumonia, defined as at least two episodes of pneumonia in 1 year or more than three at any time,25 was the referring diagnosis for 23 children (53%); in 8 children, recurrent pneumonia started after an episode of lower respiratory tract infection complicating pertussis (n = 4; 9% of the total) or measles (n = 4; 9% of the total). Other diagnoses were primary ciliary dyskinesia with situs viscerum solitus (11 patients; 26%), severe gastroesophageal reflux disease (3 patients; 7%), primary immunodeficiency (3 children; 7% [common variable immunodeficiency, in 2 patients; hyper-IgM syndrome, 1 female patient]), atypical CF phenotype (3 patients; 7%) diagnosed on the basis of two CF gene mutations ({Delta}F508/3849 + 10Kb C->T in 2 patients, and N1303K/D1152H in 1 patient), and normal sweat chloride and pancreatic sufficiency.26

Imaging Study
All children underwent chest HRCT scanning as a part of their routine follow-up. The HRCT scan was performed using a spiral instrument with 1.5 mm collimation and a 1.9-s scan time at 130 kV and 50 to 75 mA settings, and an interval of 8 to 10 mm at full inspiration with the patient in the supine decubitus position. Images were reconstructed using a bone algorithm. The extent of bronchiectasis, the severity of bronchial wall thickening, and the severity of bronchial wall dilatation were recorded on each bronchopulmonary segment using the Reiff scoring system.27 In this system, each lobe is scored for (1) the extent of involvement (0 to 2 points), (2) the severity of bronchial dilatation (0 to 3 points), and (3) the severity of bronchial wall thickening (0 to 3 points), giving a maximum total score of 48. The HRCT scan images were evaluated independently and in a blinded fashion by two pediatric radiologists. Both of them were unaware of the patient’s history or of any clinical result that could have biased their judgment of the HRCT scan imaging. All scans were presented in a random, independent order. Observations were made on six lobes, with the lingula being regarded separately, at a segmental level (18 segments). The sum of the segmental scores resulted in lobar scores, and the total score was obtained by adding together the lobar scores.

Lung Function, Microbiological, and Clinical Evaluation
FVC and FEV1, expressed as percent predicted, and the reversibility of airflow limitation after albuterol administration were evaluated in all cooperating patients.28 Therapy with short-acting or long-acting ß2-agonists was stopped 6 or 12 h, respectively, before testing. Deep throat or sputum cultures were also obtained at the same time of HRCT scanning.

The following clinical data were evaluated: age at onset of persistent or recurrent cough; and the presence of asthma, diagnosed on the basis of cough and wheeze that required bronchodilator and antiinflammatory therapy, and of the demonstration of reversible airflow limitation in collaborating children. Atopy was evaluated by skin-prick tests, and the most common seasonal and perennial local allergens were tested, including house dust mites, dog and cat dander, Aspergillus fumigatus, Alternaria alternata, Graminaceae pollen mix, Artemisia vulgaris, Parietaria officinalis, and Olea europaea pollen. The ethics review board of the hospital approved the retrospective study, and did not require informed consent.

Statistical Analysis
The results were expressed as the mean ± SEM. Comparisons were made using the Mann-Whitney U test, the Fisher exact test, and the {chi}2 test. The Spearman rank correlation coefficient ({rho}) and the Kendall {tau}-b coefficient assessed correlations among variables. Interobserver agreement was expressed as the {kappa} coefficient.29 A two-sided p value of < 0.05 was significant. The data were analyzed with a statistical software program (SPSS-PC, release 11.5; SPSS; Chicago, IL).

Results

The median (± SEM) age at HRCT scan was 8.2 ± 0.6 years (range, 0.08 to 15.4 years). Sixty-five percent (28 of 43 patients) had bilateral bronchiectasis, while patients with monolateral disease had right lung involvement (10 of 15 patients; 67%) or left lung involvement (5 of 15 patients; 33%). The percentages of lobes affected from most common to least frequent were as follows: right lower lobe, 65% (28 of 43 patients); middle lobe, 56% (24 of 43 patients); left lower lobe, 51% (22 of 43 patients); right upper lobe, 37% (16 of 43 patients); lingula, 30% (13 of 43 patients); and left upper lobe, 30% (13 of 43 patients) [{chi}2 = 18.4; p = 0.002]. Forty-four percent (19 of 43 patients) had three or more lobes involved, 26% (11 of 43 patients) had two lobes involved, and 30% (13 of 43 patients) had monolobar disease ({chi}2 = 3.6; p = 0.2). Only five patients (12% of the total) had evidence of bronchiectasis in all lobes. The total mean HRCT scan score was 20 ± 2.6. Interobserver agreement was excellent ({kappa} = 0.97).

Spirometry was performed in all the 37 cooperating patients. The mean FVC and FEV1 were 89.6 ± 3.4% predicted and 79.2 ± 4% predicted, respectively. As shown in Table 1 , no significant correlation was found between the total HRCT scan score or subscores of the extent of bronchiectasis, the severity of bronchial wall thickening, the severity of bronchial wall dilatation, and FEV1 or FVC.


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

  		Table 1. Correlations Between Total HRCT Score and Subscores, and PFT Results

 
PFT results were also analyzed separately in patients with a total HRCT score of ≤ 20 (n = 24) or > 20 (n = 13). Even though there was a trend toward worse lung function in children with more severe bronchiectasis score, FVC or FEV1 in the two groups was not significantly different (FVC, 93% vs 83% predicted, respectively [p = 0.3]; FEV1, 83% vs 72% predicted, respectively [p = 0.2]) [Table 2 ]. Figure 1 illustrates the HRCT scan of a 14-year-old boy with bronchiectasis and history of recurrent pneumonia who showed normal lung function (FVC, 116% predicted; FEV1, 106% predicted) but significant structural damage (bronchiectasis total HRCT scan score, 39).


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

  		Table 2. FVC and FEV1 % Predicted in Cases With Bronchiectasis Total HRCT Scores of ≤ 20 and > 20, Respectively

 

Figure 1
View larger version (160K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 1. HRCT scan of a 14-year-old boy with bronchiectasis and a history of recurrent pneumonia who showed normal lung function (FVC, 116% predicted; FEV1, 106% predicted) but significant structural damage (bronchiectasis total HRCT scan score, 39).

 
In 23% (10 of 43 patients), no organisms were isolated. Haemophilus influenzae and Pseudomonas aeruginosa were the most frequently detected (46% and 33% of patients, respectively). Additional organisms included Staphylococcus aureus (23%), Streptococcus pneumoniae (14%), and Klebsiella pneumoniae (7%).

An analysis of the clinical data showed that the mean age at the onset of persistent or recurrent cough was 2.2 ± 0.4 years (range, 0.08 to 9 years). Seventy-four percent (32 of 43 children) also had asthma, experiencing at least two exacerbations per year prior to the HRCT scan. In patients with asthma, we found a mean FEV1 response to albuterol of 12.2 ± 0.6%.

Thirty percent of the study population (13 of 43 patients) had positive results of the skin-prick tests. The majority of atopic patients had positive culture findings (one vs nine, respectively; p = 0.02). The same was true in the 32 asthmatic children (positive culture findings, 29 patients; negative culture findings, 3 patients; p < 0.01). Positive culture results were also significantly higher in children < 2 years of age at the time of onset of cough (25 vs 4, respectively; p < 0.01) [Table 3 ]. In addition to this, we also found that positive culture findings and asthma were more common in these children than in those who were > 2 years of age at the onset of symptoms (25 vs 8, respectively [p < 0.01]; and 25 vs 7, respectively [p < 0.01]).


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

  		Table 3. Number of Patients With Asthma and Atopy, and Subjects < 2 Years of Age at the Onset of Cough in Groups With Positive or Negative Deep Throat or Sputum Culture Findings*

 
As expected, the lower the age at the onset of cough, the lower the age at HRCT scan (r = 0.4; p = 0.004), but also the higher the prevalence of asthma (r = 0.3; p = 0.01). However, the age at the onset of cough and the age at HRCT scan were not associated with the total HRCT scan score (r = –0.2, p = 0.1; and r = 0.1, p = 0.4, respectively).

Discussion

In this study of pediatric bronchiectasis of different etiologies, we found that the disease may coexist with normal lung function since substantial structural damage was evident on HRCT scans in the absence of abnormalities found on PFT results. This supports the conclusion that although lung function measurement, combined with clinical symptoms, helps to suspect bronchiectasis, it is not a tool for the early identification of the disease,811 as previously found also in CF patients.19202122

Conflicting results on the relationship between PFT results and bronchiectasis HRCT scan score have been published. A significant association has been demonstrated in 37 New Zealand non-CF children who showed significant abnormalities of both lung function and structure in approximately 50% of cases.9 However, these patients appeared to be more severely compromised than ours since bilateral bronchiectasis was found in 87% of patients, and bronchiectasis was detected in all lobes in 20% of the patients. A similar correlation was reported by an additional study11 of 16 children with postinfectious bronchiectasis, or with CF or primary ciliary dyskinesia-associated bronchiectasis. However, in this study spirometry results were normal in all but two children, the vast majority of patients had slightly abnormal HRCT scan findings, and finally the only two children with the most severe HRCT scan score showed normal FEV1 values.

Conversely, the HRCT score correlated poorly with PFT results in 27 Aboriginal Australian children with bronchiectasis due to recurrent pneumonia.8 Our data confirmed this finding in a larger sample of patients. A possible explanation to our observation includes the evidence of mild-to-moderate HRCT scan structural changes (resulting in a total score of ≤ 20) in 65% of our patients who also performed PFTs and the localized nature of the structural changes in 35% of the study population. Furthermore, the great variability of normal lung function in children and physiologic compensatory mechanisms may easily mask early nonhomogeneous and localized changes in airways parenchyma since spirometry provides a global estimate of lung integrity.

The concept that spirometry might not detect early changes in lung parenchyma has been suggested by the results of longitudinal studies in CF patients. In these patients, normal or stable spirometry findings have been observed in association with significant HRCT scan changes due to bronchiectasis, and this supported the suggestion that pulmonary function is not an accurate method for monitoring the progression of CF lung disease.20212223 An additional study30 that was performed on lung resection specimens demonstrated that bronchial wall thickening is proportional to airway inflammation severity in adults with COPD and normal to slightly reduced FEV1.

The finding from the current study that HRCT scan subscores, including bronchial wall thickening severity, do not correlate with FEV1, the major functional marker of pulmonary disease, further reinforces the conclusion that, in many children with bronchiectasis, structural abnormalities may not be extrapolated by lung function. This is not surprising since spirometry provides a global measure of lung function integrity and gives no clues to the specific contribution of each lung or lobe, whereas, on the other hand, areas with localized moderate-to-severe structural abnormalities can be feasibly demonstrated on HRCT scans.

One limitation to our study is that patients had different etiologies for bronchiectasis, and because of the small sample size it was not possible to make a reliable statistical analysis within and between each subgroup. Therefore, our findings need to be confirmed in larger groups of patients, at least in those with immune defects or primary ciliary dyskinesia-associated bronchiectasis. Given that lung function may be preserved in the face of even severe radiographic bronchiectasis, a relevant question to be addressed is which tools can be used to predict or to check the progress of the disease, since there is little consensus on the ideal follow-up in children with non-CF bronchiectasis.6

Common clinical symptoms and signs of bronchiectasis at disease presentation or during the clinical course include productive cough and crackles at lung auscultation.31 Sputum production or viscosity has not been included within the outcomes of drug efficacy in clinical trials of patients with CF or non-CF bronchiectasis.323334 Nonetheless, many children with bronchiectasis may present before an age when sputum is normally expectorated.35 Finally, among the methods proposed for the computerized analysis of crackles,36 the sonogram analysis in a time-expanded waveform display appears to be a highly sensitive tool for crackles counting.37 Unfortunately, it requires an equipment that is not frequently available even in tertiary care centers. In a study of adults with non-CF bronchiectasis, systemic markers of inflammation, such as total WBC count, neutrophil count, and erythrocyte sedimentation rate have been reported to correlate with disease severity even though no difference between infected and noninfected patients, as depicted by sputum culture findings, could be documented.38 This, and the additional possible interference of upper respiratory tract infections, which frequently occur in children, may limit the usefulness of systemic markers of inflammation in the follow-up of pediatric patients.

A role for the exercise tolerance test in the assessment of bronchiectasis severity has been suggested,18 but no correlation with HRCT scan findings was found in non-CF children, suggesting that it must be considered a complementary test in the follow-up of patients.39 Finally, the deposition of inhaled radioaerosol has been reported40 to be diminished or nonhomogeneous in most patients with bronchiectasis, and abnormal ciliary beat frequency was also demonstrated in affected adults,41 suggesting that mucociliary clearance may be abnormal in patients with bronchiectasis. However, the mucociliary transport evaluation is technically demanding and is associated with the exposure to radioactive materials, and ciliary beat abnormalities do not appear to be related to relevant clinical parameters.41

There is growing awareness that chest HRCT scanning can be used as a biomarker for bronchiectasis since pathologic correlation studies42 have demonstrated that HRCT scan images are similar to pathologic specimens. In addition to this, the graphic images can be transformed into quantitative data (ie, scores) that are used to track the clinical course.43

CF is a clinical condition in which the role of chest HRCT scanning has been broadly investigated.43 FEV1 is the only surrogate marker currently accepted by the US Food and Drug Administration for CF lung disease.44 However, a recent longitudinal study45 has demonstrated that HRCT scan score, and not PFT results, significantly correlates with a true indicator of respiratory morbidity (ie, the number of pulmonary exacerbations). This result provides further support for the use of HRCT scanning as a valid end point in CF. Pending longitudinal studies on larger groups, this might be true also for non-CF bronchiectasis. At this regard, Edwards and coworkers9 proposed that HRCT scanning be used to monitor children with non-CF bronchiectasis to provide a more precise score in long-term follow-up.

Monitoring patients with bronchiectasis is extremely important since the disease may either deteriorate or improve. Actually, improvement following appropriate therapeutic interventions was demonstrated by the studies of Field46 reporting a fall in the annual hospitalization rate after medical or surgical treatment. Two anecdotal reports4748 of non-CF patients have shown near resolution of bronchiectasis after treatment with Nissen fundoplication plus gastrostomy in a child with chronic aspiration47 or after a course of azithromycin therapy in an adolescent patient who had undergone a heart-lung transplant with chronic lung rejection.48 Another report49 of 33 patients with bronchiectasis has shown that long-term treatment with azithromycin resulted in a significant reduction of infectious exacerbations, and in the improvement of several lung function parameters and clinical symptoms. Provided that these findings are confirmed by longitudinal and placebo-controlled evaluations in larger study populations, we speculate that HRCT scanning, alone or combined with PFTs, is likely to also be considered an outcome measure for therapeutic interventions in patients with non-CF bronchiectasis.

Another point which needs consideration is the possible relationship between asthma and bronchiectasis. A high prevalence of asthma has been reported in children with bronchiectasis.35051 This was the case also for our patients. It is tempting to speculate that inflammatory changes associated with reactive airways disease likely worsen mucociliary clearance after severe or recurrent pneumonia, thus contributing to progressive bronchial wall injury. In other words, the association between bronchiectasis and asthma can be explained by a common denominator (ie, pneumonia), since either pneumonia can precede the onset of asthma5253545556 or asthma can be a risk factor for pneumonia.57585960 The fact that in our study the majority of children were nonatopic does not diminish the relevance of the observation since bronchial inflammation is also well-documented in patients with nonallergic asthma, a condition that may have a more severe clinical course later in life.61 Interestingly, Chang and coworkers7 demonstrated bronchial inflammation with a predominant neutrophilic, and not eosinophilic, component in 58% of pulmonary lobes from indigenous Australian children with non-CF bronchiectasis who were undergoing bronchoscopy and BAL.

Conclusions

In the current study, we found that normal lung function may coexist with structural abnormalities on an HRCT scan. This lead us to reflect on the fact that in children with bronchiectasis normal lung function does not exclude damage to the bronchial structure and reinforces the hypothesis that pulmonary function is not an accurate method for assessing the severity of lung disease in children with CF or non-CF bronchiectasis. Provided that longitudinal studies aimed at exploring the correlation between HRCT scans findings and pulmonary function in larger groups will be performed, we speculate that HRCT scanning findings may be considered an appropriate imaging biomarker of non-CF bronchiectasis in children.

Footnotes

Abbreviations: CF = cystic fibrosis; HRCT = high-resolution CT; PFT = pulmonary function test

All authors declare that they have not been funded by or have any involvement with organizations with a financial interest in the subject matter or materials discussed in the article. All authors declare that they have no potential conflicts of interest, real or perceived.

Received for publication December 8, 2005. Accepted for publication February 8, 2006.

References

  1. Lucaya, J, Piqueras, J, Garcia-Pena, P, et al (2000) Low-dose high-resolution CT of the chest in children and young adults: dose, cooperation, artifact incidence, and image quality. AJR Am J Roentgenol 175,985-992[Abstract/Free Full Text]
  2. Nikolaizik, WH, Warner, JO Aetiology of chronic suppurative lung disease. Arch Dis Child 1994;70,141-142[Abstract]
  3. Singleton, R, Morris, A, Redding, G, et al Bronchiectasis in Alaska Native children: causes and clinical courses. Pediatr Pulmonol 2000;29,182-187[CrossRef][ISI][Medline]
  4. Pasteur, MC, Helliwell, SM, Houghton, SJ, et al An investigation into causative factors in patients with bronchiectasis. Am J Respir Crit Care Med 2000;162,1277-1284[Abstract/Free Full Text]
  5. Karakoc, GB, Yilmaz, M, Altintas, DU, et al Bronchiectasis: still a problem. Pediatr Pulmonol 2001;32,175-178[CrossRef][ISI][Medline]
  6. Callahan, CW, Redding, GJ Bronchiectasis in children: orphan disease or persistent problem? Pediatr Pulmonol 2002;33,492-496[CrossRef][ISI][Medline]
  7. Chang, AB, Boyce, NC, Masters, IB, et al Bronchoscopic findings in children with non-cystic fibrosis chronic suppurative lung disease. Thorax 2002;57,935-938[Abstract/Free Full Text]
  8. Chang, AB, Masel, JP, Boyce, NC, et al Non-CF bronchiectasis: clinical and HRCT evaluation. Pediatr Pulmonol 2003;35,477-483[CrossRef][ISI][Medline]
  9. Edwards, EA, Metcalfe, R, Milne, DG, et al Retrospective review of children presenting with non cystic fibrosis bronchiectasis: HRCT features and clinical relationships. Pediatr Pulmonol 2003;36,87-93[CrossRef][ISI][Medline]
  10. Eastham, KM, Fall, AJ, Mitchell, L, et al The need to redefine non-cystic fibrosis bronchiectasis in childhood. Thorax 2004;59,324-327[Abstract/Free Full Text]
  11. Pifferi, M, Caramella, D, Bulleri, A, et al Pediatric bronchiectasis: correlation of HRCT, ventilation and perfusion scintigraphy, and pulmonary function testing. Pediatr Pulmonol 2004;38,298-303[CrossRef][ISI][Medline]
  12. Shah, RM, Sexauer, W, Ostrum, BJ, et al High-resolution CT in the acute exacerbation of cystic fibrosis: evaluation of acute findings, reversibility of those findings, and clinical correlation. AJR Am J Roentgenol 1997;169,375-380[Abstract/Free Full Text]
  13. Helbich, TH, Heinz-Peer, G, Eichler, I, et al Cystic fibrosis: CT assessment of lung involvement in children and adults. Radiology 1999;213,537-544[Abstract/Free Full Text]
  14. Lynch, DA, Newell, J, Hale, V, et al Correlation of CT findings with clinical evaluations in 261 patients with symptomatic bronchiectasis. AJR Am J Roentgenol 1999;173,53-58[Abstract/Free Full Text]
  15. Roberts, HR, Wells, AU, Milne, DG, et al Airflow obstruction in bronchiectasis: correlation between computed tomography features and pulmonary function tests. Thorax 2000;55,198-204[Abstract/Free Full Text]
  16. Sheehan, RE, Wells, AU, Copley, SJ, et al A comparison of serial computed tomography and functional change in bronchiectasis. Eur Respir J 2002;20,581-587[Abstract/Free Full Text]
  17. Oikonomou, A, Manavis, J, Karagianni, P, et al Loss of FEV1 in cystic fibrosis: correlation with HRCT features. Eur Radiol 2002;12,2229-2235[ISI][Medline]
  18. Koulouris, NG, Retsou, S, Kosmas, E, et al Tidal expiratory flow limitation, dyspnoea and exercise capacity in patients with bilateral bronchiectasis. Eur Respir J 2003;21,743-748[Abstract/Free Full Text]
  19. Santamaria, F, Grillo, G, Guidi, G, et al Cystic fibrosis: when should high-resolution computed tomography of the chest be obtained? Pediatrics 1998;101,908-913[Abstract/Free Full Text]
  20. de Jong, PA, Nakano, Y, Lequin, MH, et al Progressive damage on high resolution computed tomography despite stable lung function in cystic fibrosis. Eur Respir J 2004;23,93-97[Abstract/Free Full Text]
  21. de Jong, PA, Nakano, Y, Hop, WC, et al Changes in airway dimensions on computed tomography scans in children with cystic fibrosis. Am J Respir Crit Care Med 2005;172,218-224[Abstract/Free Full Text]
  22. Marchant, JM, Masel, JP, Dickinson, FL, et al Application of chest high-resolution computed tomography in young children with cystic fibrosis. Pediatr Pulmonol 2001;31,24-29[CrossRef][ISI][Medline]
  23. Brody, AS, Klein, JS, Molina, PL, et al High-resolution computed tomography in young patients with cystic fibrosis: distribution of abnormalities and correlation with pulmonary function tests. J Pediatr 2004;145,32-38[CrossRef][ISI][Medline]
  24. Naidich, DP, McCauley, DI, Khouri, NF, et al Computed tomography of bronchiectasis. J Comput Assist Tomogr 1982;6,437-444[ISI][Medline]
  25. Wald, ER Recurrent and nonresolving pneumonia in children. Semin Respir Infect 1993;8,46-58[Medline]
  26. Rosenstein, BJ, Cutting, GR The diagnosis of cystic fibrosis: a consensus statement. J Pediatr 1998;132,589-595[CrossRef][ISI][Medline]
  27. Reiff, DB, Wells, AU, Carr, DH, et al CT findings in bronchiectasis: limited value in distinguishing between postinfectious and specific types. AJR Am J Roentgenol 1995;165,261-267[Abstract/Free Full Text]
  28. American Thoracic Society.. ATS statement: standardization of spirometry, 1994 update. Am J Respir Crit Care Med 1995;152,1107-1136[ISI][Medline]
  29. Koran, LM The reliability of clinical methods, data and judgement. N Engl J Med 1975;293,642-646[ISI][Medline]
  30. Tiddens, HA, Pare, PD, Hogg, JC, et al Cartilaginous airway dimensions and airflow obstruction in human lungs. Am J Respir Crit Care Med 1995;152,260-266[Abstract]
  31. Barker, AF Bronchiectasis. N Engl J Med 2002;346,1383-1393[Free Full Text]
  32. O’Donnell, AE, Barker, AF, Ilowite, JS, et al Treatment of idiopathic bronchiectasis with aerosolized recombinant human DNase I. Chest 1998;113,1329-1334[Abstract/Free Full Text]
  33. Nasr, SZ, Kuhns, LR, Brown, RW, et al Use of computerized tomography and chest x-rays in evaluating efficacy of aerosolized recombinant human DNase in cystic fibrosis patients younger than age 5 years: a preliminary study. Pediatr Pulmonol 2001;31,377-382[CrossRef][ISI][Medline]
  34. Robinson, TE, Goris, ML, Zhu, HJ, et al Dornase alfa reduces air trapping in children with mild cystic fibrosis lung disease: a quantitative analysis. Chest 2005;128,2327-2335[Abstract/Free Full Text]
  35. Brown, MA, Lemen, RJ Bronchiectasis. Chernick, V Boat, TF Kending, EL, Jr eds. Kendig’s disorders of the respiratory tract in children 1998,538-552 WB Saunders. Philadelphia, PA:
  36. Piirila, P, Sovijarvi, ARA Crackles: recording, analysis and clinical significance. Eur Respir J 1995;8,2139-2148[Abstract]
  37. Kaisla, T, Sovijarvi, ARA, Piirila, P, et al Validated method for automatic detection of lung sound crackles. Med Biol Eng Comput 1991;29,517-521[CrossRef][ISI][Medline]
  38. Wilson, CB, Jones, PW, O’Leary, CJ, et al Systemic markers of inflammation in stable bronchiectasis. Eur Respir J 1998;12,820-824[Abstract]
  39. Edwards, EA, Narang, I, Li, A, et al HRCT lung abnormalities are not a surrogate for exercise limitation in bronchiectasis. Eur Respir J 2004;24,538-544[Abstract/Free Full Text]
  40. Isawa, T, Teshima, T, Hirano, T, et al Mucociliary clearance and transport in bronchiectasis: global and regional assessment. J Nucl Med 1990;31,543-548[Abstract/Free Full Text]
  41. Tsang, KW, Tipoe, G, Sun, J, et al Clinical value of ciliary assessment in bronchiectasis. Lung 2005;183,73-86[CrossRef][ISI][Medline]
  42. Kang, EY, Miller, RR, Muller, NL Bronchiectasis: comparison of preoperative thin-section CT and pathologic findings in resected specimens. Radiology 1995;195,649-654[Abstract/Free Full Text]
  43. Brody, AS Scoring system for CT in cystic fibrosis: who cares? Radiology 2004;231,296-298[Free Full Text]
  44. National Institute of Health.. Workshop on surrogate markers for CF. 1997 National Institute of Health. Bethesda, MD:
  45. Brody, AS, Sucharew, H, Campbell, JD, et al Computed tomography correlates with pulmonary exacerbations in children with cystic fibrosis. Am J Respir Crit Care Med 2005;172,1128-1132[Abstract/Free Full Text]
  46. Field, CE Bronchiectasis. Third report on a follow-up study of medical and surgical cases from childhood. Arch Dis Child 1969;44,551-561[ISI][Medline]
  47. Pitney, AC, Callahan, CW, Ruess, L Reversal of bronchiectasis caused by chronic aspiration in cri du chat syndrome. Arch Dis Child 2001;85,413-414[Free Full Text]
  48. Verleden, GM, Dupont, LJ, Vanhaecke, J, et al Effect of azithromycin on bronchiectasis and pulmonary function in a heart-lung transplant patient with severe chronic allograft dysfunction: a case report. J Heart Lung Transplant 2005;24,1155-1158[CrossRef][ISI][Medline]
  49. Davies, G, Wilson, R Prophylactic antibiotic treatment of bronchiectasis with azithromycin. Thorax 2004;59,540-541[Free Full Text]
  50. Chang, AB, Grimwood, K, Mulholland, EK, et al Bronchiectasis in Indigenous children in remote Australian communities. Med J Aust 2002;177,200-204[ISI][Medline]
  51. Ip, MS, So, SY, Lam, WK, et al High prevalence of asthma in patients with bronchiectasis in Hong Kong. Eur Respir J 1992;5,418-423[Abstract]
  52. Gold, DR, Tager, IB, Weiss, ST, et al Acute lower respiratory illness in childhood as a predictor of lung function and chronic respiratory symptoms. Am Rev Respir Dis 1989;140,877-884[ISI][Medline]
  53. Shaheen, SO, Barker, DJ, Shiell, AW, et al The relationship between pneumonia in early childhood an impaired lung function in late adult life. Am J Respir Crit Care Med 1994;149,616-619[Abstract]
  54. Roizin, H, Reshef, A, Katz, I, et al Atopy, bronchial hyperresponsiveness, and peak flow variability in children with mild occasional wheezing. Thorax 1996;51,272-276[Abstract]
  55. Johnston, ID, Strachan, DP, Anderson, HR Effect of pneumonia and whooping cough in childhood on adult lung function. N Engl J Med 1998;338,581-587[Abstract/Free Full Text]
  56. Castro-Rodriguez, JA, Holberg, CJ, Wright, AL, et al Association of radiologically ascertained pneumonia before age 3 yr with asthma-like symptoms and pulmonary function during childhood: a prospective study. Am J Respir Crit Care Med 1999;159,1891-1897[Abstract/Free Full Text]
  57. Eigen, H, Laughlin, JJ, Homrighausen, J Recurrent pneumonia in children and its relationship to bronchial hyperreactivity. Pediatrics 1982;70,698-704[Abstract/Free Full Text]
  58. Lodha, R, Puranik, M, Natchu, UC, et al Recurrent pneumonia in children: clinical profile and underlying causes. Acta Paediatr 2002;91,1170-1173[CrossRef][ISI][Medline]
  59. Ciftci, E, Gunes, M, Koksal, Y, et al Underlying causes of recurrent pneumonia in Turkish children in a university hospital. J Trop Pediatr 2003;49,212-215[Abstract/Free Full Text]
  60. MacIntyre, CR, McIntyre, PB, Cagney, M Community-based estimates of incidence and risk factors for childhood pneumonia in Western Sydney. Epidemiol Infect 2003;131,1091-1096
  61. Novak, N, Bieber, T Allergic and nonallergic forms of atopic diseases. J Allergy Clin Immunol 2003;112,252-262[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 Santamaria, F.
Right arrow Articles by Boner, A. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Santamaria, F.
Right arrow Articles by Boner, A. L.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS