Chest ACCP Member Benefits
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 HighWire
Right arrow Citing Articles via ISI Web of Science (18)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kim, C. K.
Right arrow Articles by White, C. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kim, C. K.
Right arrow Articles by White, C. W.
(Chest. 2001;120:1101-1106.)
© 2001 American College of Chest Physicians

Bronchiolitis Obliterans in the 1990s in Korea and the United States*

Chang Keun Kim, MD; Sang Woo Kim, MD; Joung Sook Kim, MD; Young Yull Koh, MD; Alan H. Cohen, MD, FCCP; Robin R. Deterding, MD and Carl W. White, MD

* From the Departments of Pediatrics (Drs. C. K. Kim and S. W. Kim) and Radiology (Dr. J. S. Kim), Inje University Sanggye Paik Hospital, Seoul, South Korea; the Department of Pediatrics and Clinical Research Institute (Dr. Koh), Seoul National University Hospital, Seoul, South Korea; the Department of Pediatrics (Dr. Cohen), Washington University Hospital, St. Louis, MO; and the Department of Pediatrics (Drs. Deterding and White), University of Colorado Health Sciences Center, Denver, CO.

Correspondence to: Young Yull Koh, MD, Department of Pediatrics, Seoul National University Hospital, 28 Yongon-dong, Chongno-gu, Seoul 110–744, Korea; e-mail: kohyy{at}plaza.snu.ac.kr


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Study objectives: Our current knowledge of pediatric bronchiolitis obliterans (BO) is based largely on a few small series of patients that were reported in the older literature. In these older cases, the mortality rate was high. This study was conducted to investigate the characteristics of pediatric BO cases in two different countries.

Design: We extracted specific information regarding predisposing factors, symptoms and signs, diagnostic studies, treatment, and outcome from the medical records of 31 children who received diagnoses of BO at four university medical centers in Korea and the United States in the 1990s.

Results: The large number of Asian children reflects a clustering of cases in Korea due to adenovirus and Mycoplasma pneumoniae epidemics. The characteristic diagnostic features of BO were present in 29 of 30 high-resolution CT (HRCT) studies. Seven of nine children who underwent biopsies had histologic confirmations of BO. In two patients whose biopsy results were nondiagnostic, the diagnosis was established by HRCT together with pulmonary function testing results that were consistent with nonreversible small airways obstruction. Fifteen children (48.4%) had evidence of hypoxemia. At present, all but one are alive. Patients with elevated severity-of-illness scores were observed to have increased likelihoods of lung transplantation or death.

Conclusions: We conclude that BO has a good overall prognosis and that the mortality rate has declined over the past decade. This could be related primarily to the use of HRCT for accurate diagnosis and the availability of pediatric lung transplantation. BO cases in Korea were associated with infectious epidemics, whereas those in United States had variable predisposing factors.

Key Words: bronchiolitis obliterans • infectious epidemic • Korea • mortality • United States • 1990s


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Bronchiolitis obliterans (BO) is an uncommon and severe form of chronic obstructive lung disease in children and adults that results from an insult to the lower respiratory tract.1 Pathologically, BO is characterized by bronchiectasis of the large airways and luminal obstruction with inflammation, granulation tissue, and/or fibrosis and obliteration of the small airways.2 Known etiologies include infection (particularly adenovirus and Mycoplasma pneumoniae),3 4 5 aspiration, and toxic inhalation. Other cases have predisposing factors such as Stevens-Johnson syndrome,6 lung and bone marrow transplantation,7 and connective-tissue disorders. In many cases, the etiology is unknown. Typical symptoms include chronic cough, wheezing, and exercise intolerance. The prognosis is variable.

Our current knowledge of pediatric BO, excluding lung and bone marrow transplantation patients, is based largely on case reports8 and a few small series of patients in the older literature.1 5 In these reports, diagnoses were made largely by bronchogram, ventilation-perfusion scan, and examination of lung tissue from a biopsy or autopsy. In these older cases, the mortality rate was high.

The relatively recent application of high-resolution CT (HRCT) scanning of the chest to children with respiratory disease has enhanced the ability of clinicians to diagnose BO noninvasively.9 Also, the development of pediatric lung transplantation has given some children with end-stage lung disease including BO a potential opportunity for prolonged survival. The purpose of this report was to review recent experiences with BO in children with regard to clinical presentation, etiology, current approaches to diagnosis, treatment (including transplantation), and outcome and to compare the etiology, severity, and prognosis of BO in patients in a developing country (Korea) and a developed country (the United States).


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
The medical records of children who had received diagnoses of BO between 1990 and 1999 at two university medical centers in Korea (ie, Inje University Sanggye Paik Hospital, Seoul, South Korea, and Seoul National University Hospital, Seoul, South Korea) and two university medical centers in the United States (ie, University of Colorado Health Sciences Center, Denver, CO, and Washington University Hospital, St. Louis, MO) were retrospectively reviewed.

Patients were included in the study if they had compatible clinical presentations and/or predisposing factors and at least one diagnostic study that had been indicative of BO. Predisposing factors included the following: (1) infectious disease agents, such as adenovirus, influenza virus, and M pneumoniae, that had been identified by culture, serology, and/or polymerase chain reaction (PCR); (2) a history of aspiration or toxic inhalation; (3) the presence of a skin rash that was consistent with Stevens-Johnson syndrome; (4) aspiration diagnosed by a barium swallow procedure, the presence of lipid-laden macrophages, or other studies; and (5) positive antinuclear antibodies or related autoantibodies. The adenovirus serotype was identified by the hemagglutination inhibition assay and was confirmed by a neutralization assay with type-specific reference antisera.10 The serologic diagnosis of Mycoplasma infection was based on the demonstration of a fourfold or greater increase in the titer of antimycoplasma antibodies in the sera of patients with acute disease and in those who were convalescing.

Diagnostic studies included the following: (1) a chest roentgenogram demonstrating unilateral hyperlucent lung (ie, Swyer-James syndrome)11 ; (2) HRCT demonstrating a unilateral hyperlucent lung and/or a combination of geographic hyperlucency, central bronchiectasis, and vascular attenuation12 ; or (3) a diagnostic lung biopsy. In some patients, the diagnosis of BO was supported by characteristic abnormalities of matched patchy defects in ventilation and perfusion by scintigraphy and/or pulmonary function tests (PFTs) showing severe small airways obstruction that was either irreversible or incompletely reversible with bronchodilator therapy. To narrow the focus of this study, we excluded both patients with BO that was related to lung or bone marrow transplantation and patients with BO who had organizing pneumonia.

In those patients meeting the entry criteria, we extracted specific information from the medical records regarding clinical presentation, predisposing factors, physical examination, diagnostic studies, treatment, and outcome, and this information was entered into a database. A severity-of-illness score (1, asymptomatic; 2, symptomatic with normal oxygen saturation while breathing room air under all conditions; 3, symptomatic with normal oxygen saturation while breathing room air, but abnormal oxygen saturation [ie, < 92% at sea level and < 90% in Denver, CO, at elevation 1,700 m] during sleep or exercise; 4, symptomatic with abnormal resting oxygen saturation [ie, < 92% at sea level and < 90% in Denver, CO, at elevation 1,700 m] while breathing room air; and 5, symptomatic with pulmonary hypertension)13 was assigned to each patient based on the available information in the record at the time of the initial diagnostic workup.


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
Clinical Presentation
A total of 31 children with BO were evaluated. Demographic data are presented in Table 1 . The large number of Asian children in this group reflects a clustering of cases in Korea due to an adenovirus type 7 epidemic in 1996 and a Mycoplasma epidemic in 1995. In our series, a male predominance was noted. The mean age at the onset of symptoms was 46.4 months (age range, 7 to 183 months). The mean age at the time of diagnosis was 70.3 months (age range, 10 to 224 months). The mean duration of symptoms was 23.9 months (duration range, 1 to 212 months). In Korean children, HRCT was performed and the diagnosis of BO was made after a mean interval of 13.5 months (interval range, 3 to 36 months) following acute infectious epidemics (ie, adenovirus and Mycoplasma).


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

  		Table 1.. Demographic Data for 31 Children With BO

 
Presenting symptoms and signs are shown in Table 2 . Typical symptoms, including cough, wheezing, exercise intolerance, tachypnea, and frequent respiratory illnesses, occurred in most patients. Common physical findings included crackles, wheezing, and tachypnea. In contrast, clubbing was noted in only three patients.


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

  		Table 2.. Presenting Symptoms and Signs

 
Diagnostic Studies
Chest films were diagnostic of BO in 10 of 31 cases and demonstrated characteristic changes of a unilateral hyperlucent lung (right lung, 4 cases; left lung, 6 cases) [Fig 1 ]. Characteristic diagnostic features of geographic hyperlucency (27 patients; 90.0%), central bronchiectasis (23 patients; 76.7%), and vascular attenuation (19 patients; 63.3%) were present in 29 of 30 HRCT studies that were performed (Fig 2 ). The involved areas on the HRCTs corresponded to those showing infiltrates on chest radiographs at the time of the initial pneumonia in all 25 patients with an infectious etiology. Twenty-three patients had at least two of the three findings on HRCTs. The most frequent finding was geographic hyperlucency, and 21 of the 27 patients with this finding also had central bronchiectasis. Eleven patients were investigated by scintigraphy, and all 11 had severe, matched defects of ventilation and perfusion that were consistent with the diagnosis of BO.



View larger version (89K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 1.. BO in a 22-month-old boy secondary to adenovirus type 7 infection. A plain chest radiograph 5 months after the infection shows unilateral hyperlucency in the right lower zone and a hazy increase in density in the left midzone.

 


View larger version (98K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 2.. BO in a 20-month-old boy secondary to adenovirus type 3 pneumonia. An HRCT scan taken 14 months later at the level of the right middle-lobe bronchus demonstrates extensive geographic hyperlucency, central bronchiectasis, and attenuated vessels.

 
Open or thoracoscopic lung biopsies were performed in nine children. Seven of these children had histologic confirmations of BO (Fig 3 ). The positive biopsy specimens demonstrated bronchiectasis of the larger airways, obliteration of the small airways with inflammatory cells, granulation and/or fibrous tissue, peribronchiolar inflammation and/or fibrosis, atelectasis, and reduction of vessel size and/or numbers. The diagnosis of BO was confirmed in one patient with Stevens-Johnson syndrome when the patient’s native lungs were examined following lung transplantation. In two patients with nondiagnostic biopsy results, the diagnosis of BO was established by HRCT, which demonstrated geographic hyperlucency, central bronchiectasis, and vascular attenuation, together with PFT data that were consistent with severe, nonreversible small airways obstruction.



View larger version (161K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 3.. BO in a 7-year-old girl with Stevens-Johnson syndrome. An histologic section of the bronchiole demonstrates near total occlusion by mononuclear inflammatory cells and fibrous tissue. Extensive peribronchiolar inflammation also is present (hematoxylin-eosin, original x200).

 
PFT data from 14 children are presented in Table 3 . The results are consistent with severe obstructive lung disease, air trapping, and hyperinflation. Three of the 14 children had bronchodilator responses, as indicated by an increase in FEV1 of >= 10% following salbutamol inhalation, although all patients continued to have a severe obstructive pattern on PFT results after bronchodilator therapy.


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

  		Table 3.. Pulmonary Function Data for 14 Children (> 7 Years Old) With BO*

 
BAL was performed in eight patients. BAL differential cell counts showed a significantly increased percentage of neutrophils (median, 80%; range, 3 to 98%). However, BAL was generally not helpful, except in one patient in whom M pneumoniae was isolated.

Etiology
The etiology of BO in this series, based on clinical presentation and diagnostic studies, is presented in Table 4 . In most cases, an infectious cause was found, with adenovirus alone identified most often. Adenovirus was identified by the culturing of nasopharyngeal secretions or tracheal aspirates in 12 patients, by testing the sera from patients with acute disease and from those who were convalescing in 5 patients, and by PCR of lung tissue in 1 patient. Two patients were identified by both culture and serology. M pneumoniae was identified by serology in eight patients, by PCR as well as serology in one patient, and by PCR of BAL fluid in one patient. Two patients had evidence of coinfection with adenovirus and M pneumoniae, although it could not be determined whether these infectious agents had an additive or synergistic role. Two patients developed BO following Stevens-Johnson syndrome. In four patients, no discernable etiology could be determined despite extensive evaluation.


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

  		Table 4.. Etiology of BO*

 
Treatment
In this series, long-term therapy with agents typically used in the treatment of asthma was most often prescribed. ß2-agonist therapy was used in 28 patients, inhaled corticosteroid therapy was used in 14 patients, cromolyn therapy was used in 10 patients, and theophylline therapy was used in 4 patients. Systemic corticosteroids were administered for at least 1 month in 17 patients. Although it is difficult to determine with certainty from this retrospective review, a beneficial clinical response based on improved symptoms and/or decreasing oxygen requirements was suggested in 11 patients. Other prescribed therapy included hydroxychloroquine in two patients and cyclosporine in one patient. In each instance, no beneficial response to treatment was observed. One patient had a favorable response to IV gamma-globulin infusions and a 3-day regimen of pulse IV methylprednisolone (30 mg/kg per daily dose), both given monthly. Prior to therapy, the patient had required supplemental oxygen therapy. Following each monthly regimen, his oxygen saturations improved such that he had normal oxygen saturation in room air for 3 weeks before it would decrease again, causing a resumed need for supplemental oxygen. This pattern continued for 6 months until he improved and had normal oxygen saturation levels in room air continuously without treatment.

Severity and Outcome
Fifteen children had evidence of hypoxemia demonstrated by pulse oximetry and/or arterial blood gas levels. Of these 15 patients, 7 had arterial oxygen desaturation with exercise or during sleep and 6 showed oxygen desaturation at rest. Two patients had evidence of pulmonary hypertension by ECG or echocardiogram.

Patients have been observed from 1 to 10 years after the onset of symptoms. At the current time, all patients but one are alive. The mortality rate was comparable between patients in Korea and in the United States (0% and 6.7%, respectively). One patient who received high-dose corticosteroid therapy died of disseminated varicella while awaiting lung transplantation. Three children in the United States underwent successful transplantation procedures and are currently alive 1 to 6 years after receiving the transplants. These children showed increases in pulmonary function near that predicted for healthy children after lung transplantation. The severity-of-illness score at the time of the initial diagnostic workup compared to outcome is presented in Table 5 . As expected, the data indicated that patients with more severe disease initially were more likely to require tranplantation or to die.


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

  		Table 5.. Severity-of-Illness Score and Outcome

 

   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
Our data demonstrate that BO in children is less severe than it has been known to be in the past and that the mortality rate has declined over the past decade. This could be related primarily to the use of HRCT for accurate diagnosis and the availability of pediatric lung transplantation.

To our knowledge, this is the largest series of pediatric BO patients reported to date. In contrast to older studies that utilized bronchography, ventilation-perfusion scans, and lung biopsies for diagnosis, this study demonstrates that HRCT has improved the early diagnostic approach to BO in that it is a reasonably accurate diagnostic tool. This may negate the need for bronchography and/or lung biopsy in many cases.14 In fact, the diagnosis of BO may have been missed by lung biopsy due to sampling error, as previously reported.15 In this study, BO was diagnosed with confidence in two children who had undergone nondiagnostic lung biopsies, based on PFT results indicating minimally reversible airways obstruction and characteristic HRCT findings.

The course of patients with BO varies from mild, asthma-like symptoms to rapidly progressive deterioration and death. Our experience that patients with this disease have a good overall prognosis and a relatively low mortality rate is different from that reported by Hardy et al1 This is due in large part to a difference in the way the cases were identified. In the study by Hardy et al,1 approximately half the cases were discovered by reviewing autopsy records. In contrast, most cases in our study were identified through the use of HRCT, which is a highly sensitive diagnostic study of small airway lesions.12 The less severe nature of BO in our series, therefore, may have been in part due to the inclusion of mildly affected patients who otherwise would have been considered as having a sequela of adenovirus or Mycoplasma infection rather than having BO. Pediatric lung transplantation is now an available option for patients who are estimated to have a life expectancy of < 1 year.16 Without a lung transplant, three patients in our population may not have survived, which would have increased the mortality rate. Our data indicate that BO in children is not as lethal as has been reported previously. Even if our observation may not be representative of BO in general, our study helps to illustrate the fact that BO, a primarily pathologic diagnosis, has diverse clinical manifestations and that the prognosis of BO is variable.

The role of adenovirus,3 M pneumoniae,17 and other infectious agents5 in the development of chronic lung disease including BO in children is well-documented. Patients with severe adenovirus pneumonia have been shown to have immune complexes containing adenovirus antigen in the lung,18 as well as increased serum levels of interleukin-6, interleukin-8, and tumor necrosis factor-{alpha}.19 These studies suggest that abnormal or excessive host immunologic and inflammatory responses may be important in the development of chronic lung disease from adenovirus infection.

Little is known about host factors that predispose the patient to BO. The maternal antibody may be protective, because the disease characteristically occurs in infants > 6 months of age. Of interest is the ethnic trend seen in BO patients. Two ethnically distinct populations of children, Polynesian children in New Zealand and Native Americans in central Canada, have been reported to be particularly susceptible to BO, suggesting that genetic or environmental factors may be important.20 Our study evaluated a population of children with BO of different ethnicities and geographic origins. BO cases in Korea were associated with infectious epidemics, whereas those in United States had variable predisposing factors. However, our findings indicate a number of similarities in the results of HRCT scans and PFTs regardless of the etiology of BO or the ethnic/geographic origin of the patient.

PFTs continue to be an important diagnostic tool in patients with BO. The results of PFTs in patients with BO characteristically show irreversible obstructive lung disease in infants21 as well as older children.14 The midexpiratory phase of forced expiratory flow (FEF25–75) is a measure of small airways disease, and a marked decrease (ie, < 30% of predicted) is a particularly sensitive indicator of BO.22 A severe obstructive process with air trapping and a decrease in the FEF25–75 level were documented in the 14 patients who were able to perform PFTs in our series. Arterial oxygen saturation can be used to grade the severity of the disease.13 Fifteen children (48.4%) had evidence of hypoxemia, suggesting that early diagnosis and treatment are potentially important to prevent secondary pulmonary hypertension.

No universally accepted protocol has been established for the treatment of BO. The use of corticosteroid therapy in the early phase of the illness in an attempt to modify the fibroblastic response has been proposed.23 In our study, a beneficial clinical response was suggested in 11 of the 17 patients (64.7%) following systemic oral corticosteroid therapy. Some patients required maintenance therapy for months or years. Four of 11 patients who benefited from the use of corticosteroids, and 5 of 6 patients who did not, could perform PFTs. Two of the former four patients and none of the latter five patients demonstrated an immediate bronchodilator response following salbutamol inhalation. Although it is difficult to determine with certainty from this small number of patients, bronchodilator responsiveness seems to be a guideline for long-term corticosteroid treatment. The use of bronchodilators is controversial because, in theory, the patients should not show improvement in fixed airway obstruction. In this study, only 3 of 14 patients with PFT data demonstrated a bronchodilator response. However, eight of those patients showed a beneficial clinical response while being treated with bronchodilators. Patients with fixed airflow obstruction, like some emphysema patients, show clinical symptomatic benefits from the repeated use of bronchodilators.24 Therefore, the decision of whether or not to prescribe bronchodilators should not be based on the one-time response to bronchodilators seen in PFTs. In those severely affected patients who are not expected to survive, lung transplantation may be a successful treatment option.


   Footnotes
 
Abbreviations: BO = bronchiolitis obliterans; FEF25–75 = midexpiratory phase of forced expiratory flow; HRCT = high-resolution CT; PCR = polymerase chain reaction; PFT = pulmonary function test

This study was supported in part by a Clinician Scientist Grant awarded in 1998 to Dr. Chang Keun Kim by Inje University, Korea, and by a year 1999 Brain Korea 21 project for Medicine, Dentistry, and Pharmacy.

Received for publication October 13, 2000. Accepted for publication May 4, 2001.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Hardy, KA, Schidlow, DV, Zaeri, N (1988) Obliterative bronchiolitis in children. Chest 93,460-466[Abstract/Free Full Text]
  2. Becroft, DMO (1971) Bronchiolitis obliterans, bronchiectasis, and other sequelae of adenovirus type 21 infection in young children. J Clin Pathol 24,72-82[Abstract/Free Full Text]
  3. Sly, PD, Soto-Quiros, ME, Landau, LI, et al (1984) Factors predisposing to abnormal pulmonary function after adenovirus type 7 pneumonia. Arch Dis Child 59,935-939[Abstract]
  4. Coultas, DB, Samet, JM, Butler, C (1986) Bronchiolitis obliterans due to Mycoplasma pneumoniae. West J Med 144,471-474[ISI][Medline]
  5. Laraya-Cuasay, LR, DeForest, A, Huff, D, et al (1977) Chronic pulmonary complications of early influenza virus infection in children. Am Rev Respir Dis 116,617-625[ISI][Medline]
  6. Kim, MJ, Lee, KY (1996) Bronchiolitis obliterans in children with Stevens-Johnson syndrome: follow-up with high resolution CT. Pediatr Radiol 26,22-25[CrossRef][ISI][Medline]
  7. Philit, F, Wiesendanger, T, Archimbaud, E, et al (1995) Post-transplant obstructive lung disease ("bronchiolitis obliterans"): a clinical comparative study of bone marrow and lung transplant patients. Eur Respir J 8,551-558[Abstract]
  8. Stokes, D, Sigler, A, Khouri, NF, et al (1978) Unilateral hyperlucent lung (Swyer-James syndrome) after severe Mycoplasma pneumoniae infection. Am Rev Respir Dis 117,145-152[ISI][Medline]
  9. Lynch, DA, Hay, T, Newell, JD, Jr, et al (1999) Pediatric diffuse lung disease: diagnosis and classification using high-resolution CT. AJR Am J Roentgenol 173,713-718[Abstract/Free Full Text]
  10. Hierholzer, JC, Gamble, WC, Dowdle, WR (1975) Reference equine antisera to 33 human adenovirus types: homologous and heterologous titers. J Clin Microbiol 1,65-74[Abstract/Free Full Text]
  11. Daniel, TL, Woodring, JH, Vandiviere, HM, et al (1984) Swyer-James syndrome-unilateral hyperlucent lung syndrome: a case report and review Clin Pediatr (Phila) 23,393-397
  12. Lynch, DA, Brasch, RC, Hardy, KA, et al (1990) Pediatric pulmonary disease: assessment with high-resolution ultrafast CT. Radiology 176,243-248[Abstract/Free Full Text]
  13. Fan, LL, Kozinetz, CA (1997) Factors influencing survival in children with chronic interstitial lung disease. Am J Respir Crit Care Med 156,939-942[Abstract/Free Full Text]
  14. Chang, AB, Masel, JP, Masters, B (1998) Post-infectious bronchiolitis obliterans: clinical, radiological and pulmonary function sequelae. Pediatr Radiol 28,23-29[CrossRef][ISI][Medline]
  15. Hardy, KA (1993) Obliterative bronchiolitis. Hillman, BC eds. Pediatric respiratory disease: diagnosis and treatment ,218-221 WB Saunders Philadelphia, PA.
  16. Noyes, BE, Kurland, G, Orenstein, DM (1997) Lung and heart-lung transplantation in children. Pediatr Pulmonol 23,39-48[CrossRef][ISI][Medline]
  17. Kim, CK, Chung, CY, Kim, JS, et al (2000) Late abnormal findings on high-resolution computed tomography after Mycoplasma pneumonia. Pediatrics 105,372-378[Abstract/Free Full Text]
  18. Mistchenko, AS, Lenzi, HL, Thompson, FM, et al (1992) Participation of immune complexes in adenovirus infection. Acta Paediatr 81,983-988[ISI][Medline]
  19. Mistchenko, AS, Diez, RA, Mariani, AL, et al (1994) Cytokines in adenoviral disease in children: association of interleukin-6, interleukin-8, and tumor necrosis factor alpha levels with clinical outcome. J Pediatr 124,714-720[CrossRef][ISI][Medline]
  20. Wohl, ME, Chernick, V (1978) State of the art: bronchiolitis. Am Rev Respir Dis 118,759-781[ISI][Medline]
  21. Teper, AM, Kofman, CD, Maffey, AF, et al (1999) Lung function in infants with chronic pulmonary disease after severe adenoviral illness. J Pediatr 134,730-733[CrossRef][ISI][Medline]
  22. Lentz, D, Bergin, CJ, Berry, GJ, et al (1992) Diagnosis of bronchiolitis obliterans in heart-lung transplantation patients: importance of bronchial dilatation on CT. AJR Am J Roentgenol 159,463-467[Abstract/Free Full Text]
  23. Moran, TJ, Hellstrom, NR (1958) Bronchiolitis obliterans. Arch Pathol 66,691-707[ISI]
  24. Guyatt, GH, Townsend, M, Pugsley, SO, et al (1987) Bronchodilators in chronic air-flow limitation: effects on airway function, exercise capacity, and quality of life. Am Rev Respir Dis 135,1069-1074[ISI][Medline]



This article has been cited by other articles:


Home page
 ChestHome page
Y. Y. Koh, D. E. Jung, J. Y. Koh, J. Y. Kim, Y. Yoo, and C. K. Kim
Bronchoalveolar Cellularity and Interleukin-8 Levels in Measles Bronchiolitis Obliterans
Chest, May 1, 2007; 131(5): 1454 - 1460.
[Abstract] [Full Text] [PDF]

Home page
 ThoraxHome page
K J Smith and L L Fan
Insights into post-infectious bronchiolitis obliterans in children.
Thorax, June 1, 2006; 61(6): 462 - 463.
[Full Text] [PDF]

Home page
 ThoraxHome page
A J Colom, A M Teper, W M Vollmer, and G B Diette
Risk factors for the development of bronchiolitis obliterans in children with bronchiolitis
Thorax, June 1, 2006; 61(6): 503 - 506.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
Y. Yoo, J. Yu, D. K. Kim, S. H. Choi, C. K. Kim, and Y. Y. Koh
Methacholine and adenosine 5'-monophosphate challenges in children with post-infectious bronchiolitis obliterans
Eur. Respir. J., January 1, 2006; 27(1): 36 - 41.
[Abstract] [Full Text] [PDF]

Home page
 PediatricsHome page
J. J. Fullmer, L. L. Fan, M. K. Dishop, C. Rodgers, and R. Krance
Successful Treatment of Bronchiolitis Obliterans in a Bone Marrow Transplant Patient With Tumor Necrosis Factor-{alpha} Blockade
Pediatrics, September 1, 2005; 116(3): 767 - 770.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
J. H. Ryu, J. L. Myers, and S. J. Swensen
Bronchiolar Disorders
Am. J. Respir. Crit. Care Med., December 1, 2003; 168(11): 1277 - 1292.
[Abstract] [Full Text] [PDF]

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 HighWire
Right arrow Citing Articles via ISI Web of Science (18)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kim, C. K.
Right arrow Articles by White, C. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kim, C. K.
Right arrow Articles by White, C. W.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS