Obliterative Bronchiolitis in Children

Obliterative Bronchiolitis in Children* Karen Ann Hardy, M.D., F.C.C.P.;t Daniel ~ Schidlow, M.D., F.C.C.P.;* and Nayereh Zaeri, M.D.§

Clinical, radiologic and histologic features of obliterative bronchiolitis (OB) in children were reviewed to de6ne features helpful in early recognition. All autopsies (n = 2,897), lung biopsies (n = 144), and medical records of children followed at St. Christopher's Hospital for Children (SCRC) between 1960 and 1985 were screened. Nineteen cases of 08 were con6rmed using radiologic and histologic criteria. 1Welvepatients were diagnosed during life, and ten survived. Seven were diagnosed post mortem. OB should be considered when persistent respiratory signs and symptoms

followacute pneumonia, aspiration is known or suspected, areas or hyperlucency are seen on chest radiograph, or respiratory failure with overaeration is unresponsive to therapy. Diagnostic studies include ventilation-perfusion scan, bronchography and lung biopsy. Sequelae include dyspnea on exertion, obstructive lung disease, bronchiectasis, persistent atelectasis, and hyperlucent lung syndrome. Recognition and supportive treatment during the acute and chronic phases may improve the functional status or these patients.

Obliterative bronchiolitis (OB) is an infrequent disorder characterized by partial or complete obstruction of bronchi and bronchioles by fibrous tissue following an insult to the lower respiratory tract. Following the initial injury and subsequent epithelial sloughing, fibroblastic proliferation leads to the occlusion of airways by polypoid masses or' concentric scarring. Reported sequelae include chronic atelectasis,' bronchiectasis," and unilateral hyperlucent lung syndrome.Y In the pediatric population, OB has most frequently been preceded by respiratory tract infection caused by adenovirus.?? influenza," or measles. 9 Several patients at SCHC developed OB over the last few years following infection or recurrent aspiration. The variable prognosis and recent increased incidence prompted us to review the past 25 years' experience at SCHC to define the clinical course and diagnostic studies allowing earlier diagnosis of OB in children.

period were screened in an effort to diagnose previously undetected cases. All patients with cystic fibrosis and bronchopulmonary dysplasia were excluded from the analysis since OB is considered a component of these basic pathologic processes. Clinical information and follow-up data were obtained from the patients' records, the pulmonary physicians, the parents and the patients. A pathologist (NZ) examined autopsies and biopsies with the diagnosis of OB, bronchiolitis, necrotizing bronchiolitis and bronchopneumonia. Histologic diagnosis of OB was made by the detection of either cellular masses composed offibroblasts, leukocytes, and fibrin which partially or fully obstructed the airway lumen, or constrictive concentric scarring causing obstruction." Original tissue blocks were reprocessed with hematoxylin-eosin, Masson's trichrome, methenamine silver and Verhoeff-VanGiesons elastic stains. A radiologist reviewed the original radiographs and made the diagnosis by matched ventilation-perfusion defects and bronchographic changes including obstruction to filling of the peripheral bronchi, terminal bronchioles, and alveoli with ballooning of the distal end of the airway when positive airway pressure was applied.

MATERIALS AND METHODS

All records of children admitted to St. Christopher's Hospital for Children (SCHC) or followed at the Pulmonary Center between 1960 and 1985were screened for diagnoses ofOB. Allautopsies (n = 2,897) and lung biopsies or lobectomies (n = 244) during the same time *From the Section of Pediatric Pulmonology, Departments of Pediatrics and Pathology, Temple University School of Medicine, Saint Christopher's Hospital fOr Children, Philadelphia. This work has been partially funded by grants from the Division of Maternal and Child Health, Department of Health and Human Services (training grant MCl 009021-05), a Cystic Fibrosis Center Grant from the Cystic Fibrosis Foundation, and a research fellowship from the American Lung Association. tPresently Assistant Professor of Pediatrics, University of California, San Francisco. *Associate Professor of Pediatrics, St. Christopher's Hospital for Children. §Assistant Professor, St. Christopher's Hospital for Children. Manuscript received March 16; revision accepted August 6. Reprint requests: Dr. Hardy, M 1303, University of California Medical School, San Francisco 94143

RESULTS

Nineteen cases of OB were confirmed comprising two groups. Group 1 included 12 patients (ten boys, two girls) diagnosed during life. Group 2 included seven patients (six boys, one girl) identified by review of autopsy specimens.

Group 1 (12 patients) The age of onset of symptoms ranged from three months to 13.5 years (mean three years). All patients presented during winter months with symptoms of pneumonia including tachypnea, fever, and cough. A "flu-like" illness with vomiting, malaise, myalgias and anorexia was seen in eight cases (Table 1). Crackles, usually localized, were heard in all patients, and diffuse wheezing was present in eight patients during the initial episode. All initial chest radiographs were abnormal. Diffuse interstitial and peribronchial infiltrates were common with patchy confluent densities in localized areas. Obliterative Bronchiolitis in Children (Hardy, Sehid/ow, Zaer/)

Table l-CUnical Picture

Case

Age at Onset" (yrs)

1 2 3 4

13.5 3.5 2 1.83

5

6 7 8 9 10 11 12

5

.25 1.25 2.58 3.5 .58 .67 1.75

~ 12 Patients

with ObUterative Branchiolitil

Acute presentationj

Presumed Etiologyt Mycoplasma Influenza Influenza Parainfluenza 3 Measles S aurew Adenovirus GER Mycoplasma GERlRSV

IP

RF/MV

S

VS

+ +

+

+

+

+ + +

+

+

+

+

+

+

+ + + +

+ + + +

Chronic Obstruction

+ + + + +

+ + +

+ + + +

+ + + +

+

+

Years Followed

4.5 13.5 14.5 9.5 21 Lost to follow up 6 11.5 2.5 1.5

Died at 4 Died at 30 months

*Mean age= 3 years. tCulture proven (cases 2, 3, 6, 7), four fold rise in titers (cases 1, 4, 9, 10),clinical diagnosis based upon cough, coryza, conjunctivitis, Koplik spots (case 5), initial hospitalization elsewhere, no viral studies done (case 11), autoimmune hemolytic anemia (case 12). *GER-gastroesophageal reflux, IP-inpatient, RF/MV-respiratory failure, mechanical ventilation, RSV-respiratory synticial virus, Ssteroids used, VS-viral syndrome.

Atelectasis was seen in four patients (Table 2). Ten patients required hospitalization. All patients

had normal sweat electrolytes, alpha-antitrypsin levels, and serum immunoglobulins with negative tuber-

Table 2-0bliteraOOe BronchioUtiB in Patienta DiGgnoatic Studia* Case

Chest radiograph

1

LLL atelectasis Left: lung bullae Linear markings and confluent densities RML, RLL, LLL Infiltrates left lung and RUL

2

3 4

5 6

7

8 9

10

Bilateral PBT Hyperlucent lung Bilateral PBT Hyperlucent lung Infiltrates RML, RLL Atelectasis RUL LLL infiltrate Atelectasis LLL infiltrate Atelectasis Hyperlucent left lung

11

Patchy infiltrates bilaterally overaeration Diffuse infiltrates

1~

Diffuse infiltrates

Bronchoscopy

Matched defects of ventilation/perfusion

Pruned tree bronchogram

NL

LLL

LLL

NL anatomy Friable mucosa

Patchy areas on right LLL Patchy areas on right

NL anatomy Friable mucosa

Left lung and RUL

LLL

NL

LLL Patchy areas of LUL Very decreased perfusion LLLt NL perfusiont

LLL

NL NL

Biopsy

Focal emphysema

Bilateral

No bronchioles DB

Interstitial pneumonia, chronic inBammation

LLL RUL

NL

LUL,LLL some right NA

LLL

Extensive OB

NA

Left lung, RUL

LLL

NL

Yes

NA

Focal emphysema chronic bronchiolitis (2 bronchioles) OB, interstitial fibrosis

Bilateral inflammation NA

Bilateral

Bilateral

Focal emphysema

NA

NA

OB, interstitial pneumonitis diffuse alveolar damage

NL

LUL, LLL

*LLL = left lower lobe; LUL = left upper lobe; NL = normal; NA= not applicable; OB = obliterative bronchiolitis; PBT = peribronchial thickening; RLL=right lower lobe; RML=right middle lobe; RUL=right upper lobe. tPulmonary angiography. *Female patient. CHEST I 93 I 3 / MARCH, 1988

481

culin skin tests and negative gastric washings for hemosiderin-laden macrophages. During the acute phase, all patients were given therapy with antibiotics, bronchodilators, and chest physiotherapy. Intravenous corticosteroid therapy was administered to six patients; one of these (case 12) developed OB while receiving daily steroids for autoimmune hemolytic anemia. Pneumothorax complicated the course of two of four patients requiring mechanical ventilation . Infection was confirmed in eight patients by isolation of a virus or a fourfold rise in serum titers (Table1). Measles was diagnosed in another patient (case 5) by clinical criteria. Case 6 had staphylococcal pneumonia, possibly complicating an unidentified viral infection. Severe gastroesophageal reflux (GER) and aspiration was considered to be the major predisposing factor to the development of OB in cases 8 and 10. Case 8 had undergone repair of a tracheoesophageal fistula during the neonatal period. He suffered recurrent episodes of pneumonia and bronchospasm and the diagnosis ofOB of the left lower lobe was made at four years of age. Resection of the lobe decreased the frequency of such episodes, though it did not eliminate them. At seven years of age, severe esophageal dysmotility and aspiration was confirmed. Case 10was admitted for vomiting,

fever, cough and hypoxemia. He developed persistent bronchospasm requiring prolonged hospitalization . He then contracted respiratory synticial virus infection necessitating 5 days of mechanical ventilation. Massive gastroesophageal reflux (GER) and aspiration was confirmed by barium swallow20 days after admission; lung biopsy documented OB nine days later. The respiratory symptoms of both patients abated significantly following anti-reflux surgery. Diagnostic studies in these patients are summarized in Table 2. Chest radiographs at the time of diagnosis were minimally abnormal. Infiltrates seen during the acute illness partially resolved in most. Atelectasis persisted in four patients. Hyperlucent lung syndrome was already present in one patient. The unexpected finding of marked ventilation/perfusion abnormalities on a lung scan in one early case led to the subsequent routine use of this diagnostic test. Scattered areas of matched decrease in ventilation and perfusion were seen in all scans (n =8). Twopatients evaluated prior to 1970 underwent cardiac catheterization to assess pulmonary blood flow. Patient 5, with hyperlucent lung syndrome and an abnormal ventilation scan, had matched areas of markedly decreased flow to the entire right lung and portions of the left lung and mildly

FIGURE 1. Radiographic studies of case 1. a and b, (upper left and right). Plain frontal and lateral films showing left lower lobe atelectasis and infiltrates. c (lower left). Patchy areas of decreased ventilation are seen (posterior view). d (lower right). Inspiratory and expiratory views of the left lung . Ballooning of the obliterated airways is clearly seen on insufflation.

462

0bI~8rative

Bronchlomls In Children (Herdy, Sehld/ow. Zaerl)

FIGURE 2. Photomicrograph (200 x ) from case 16 shows a polypoid lum inal mass of an organizing exudate occluding the bronchiole. Peribronchial inflammatory infiltrate is evident.

increased pulmonary pressures; patient 6 had a normal angiogram. Examination with the rigid bronchoscope showed normal anatomy in all patients examined (n =10)with minor mucosal abnormalities in three. Bronchography was perfurmed in ten patients. Saccular bronchiectasis with ballooning of the airways at the blind end when distended by positive pressure was uniformly present (Fig 1). Passage of contrast medium into the alveoli did not occur even with insufflation of the lungs. Open lung biopsy was performed in eight patients and documented OB in four (cases 2, 8, 10 and 12). Diverse pathologic findings were present in association with OB in these specimens (Fig 2). Biopsies 2 and 8 had OB with little parenchymal involvement. Biopsy 10 contained focal interstitial infiltrate around the bronchioles and a cholesterol cleft granuloma. Biopsy 12 showed severe diffuse alveolar damage on both biopsy and subsequent autopsy material. Biopsy 1 showed areas offocal emphysema and pleural thickening with no airways available for examination. The remaining biopsies (patients 3, 9 and Il) showed emphysema with variable degrees of chronic bronchitis and bronchiolitis though only one to three airways were present per specimen.

Of the 12 patients, nine slowly recovered from their acute illness with residual symptoms; five required readmission for bronchospasm and pneumonia. Sixare dyspneic on exercise and limit their participation in physical activities. Physical examination is remarkable for persistent crackles and intermittent wheezing not consistently responsive to bronchodilator therapy. Clubbing is present in three. Sputum cultures rarely show colonization with pathogenic organisms (case 2, nontypeable Hemophilus influenzae; case 10, Klebsiella oxytoca.) Atelectasis persisted in four patients, and hyperlucent lung syndrome followed localized disease in three patients. An obstructive process with air trapping was documented in six of the seven patients able to cooperate for pulmonary function testing (Table 3). Patient 4 demonstrates a restrictive pattern and has chronic wheezing unresponsive to bronchodilator therapy. Seven patients from this group are maintained on chronic bronchodilator therapy. Two patients died. Case 11had severe pneumonia at eight months of age and was admitted for treatment. Over the next two years he was admitted seven times for recurrent pneumonia and bronchospasm and was eventually referred to SCHC for progressively severe respiratory impairment. The diagnosis of OB with severe bronchiectasis was made. He did not return for follow-upand died at home within five months. Case 12 developed autoimmune hemolytic anemia at 18 months of age. Three months later, while on daily steroid therapy, she developed respiratory distress with diffuse infiltrates on radiographic examination . She gradually developed increasing respiratory distress with shortness of breath and chronic hypoxemia with persistently negative bacterial, viral, and fungal cultures. Open lung biopsy at 30 months of age showed extensive OB. She later died due to respiratory failure and Klebsiella septicemia. Autopsy revealed extensive OB with interstitial pneumonitis. The remaining patient was lost to follow-up one year after diagnosis .

Croup 2 (seven patients) There are few characteristics common to these patients (Table 4.) Mean age at the onset of respiratory

Table 3-Pulmonary Function Tests in Patients with Obliterative Bronchiolitis· Case

Yr since onset

FVC

FEV/FVC (%)

MMEFR (%)

TLC (HE) (%)

1 2 3 4 5 8t 9

2 12 7 8 9 9 .8

89 57 69 70 75 59 67

40 42 75

19 13 42 112 15

106

85 36 64 80

34

70

84

awnc (HE) (%) 29.5 43.5

109

50

136 26 113

50

63

22

41

55

*Values given as percent of predicted. . . . ) _ tall FVC =forced vital capacity; FEV, =forced expiratory volume in one second; MMEFR = mid maximal expiratory flow rate; TLC (HE - to ung capacity helium method; RV= residual volume. tTests done following left lower lobectomy. CHEST I 93 I 3 I MARCH. 1988

483

Table 4-Summary ofPatients Retrospectively Diagnoaed with Obliterative Bronchiolitia (Group 2)

Case

History

13

Dysmorphic term infant, severe GER, aspiration pneumonia 30 week twin A, respiratory distress Congenital heart defects Right middle lobe pneumonia Cerebal palsy Bums Pneumonia Congestive heart failure pneumonia, arrhythmias Multiple congenital anomalies DiGeorge syndrome GER, pneumonia Recurrent pneumonia pneumocystis

Management IC

14 15 16t 17 18 19

Age at Death(yrs)

RF/MV

Pathologic Diagnoses

+

+

+

.25

OB, foreign body granuloma, severe patchy bronchopneumonia

+

+

+

.25

OB, organizing pneumonia

+

+

+

5

+

+

+

12

+

+

+

2

+

+

+

1.33

+

+

+

.75

OB, complex congenital heart disease OB, esophagitis, organizing pneumonia OB, cardiomyopathy, patchy bronchopneumonia o B (constrictive), DiGeorge syndrome OB, Pneumocystis pneumonia diffuse alveolar damage

GER = gastroesophageal reflux; IC = intensive care; RF/MV = respiratory failure/mechanical ventilation. ·Mean age=3.1 y. tFemale patient.

distress was three years, ranging from one day to 12 years. Six were boys. None received steroid therapy during their acute illness. All experienced hypoxemia and respiratory failure; all were mechanically ventilated. Air trapping complicated ventilator management in all, and pneumothorax occurred in three. GER and recurrent aspiration was documented prior to death in two (cases 13, 18)and was suggested at autopsy in two others (cases 16, 17). Patient 16 was a 12-year-old girl with cerebral palsy, spastic quadriplegia and mental retardation secondary to birth asphyxia who was admitted for treatment of burns. At autopsy four days later, OB was present with lipid-laden macrophages, foreign body granuloma and cholesterol clefts throughout her lungs with basal cell hyperplasia of the esophagus at the gastroesophageal junction and distal esophagus. Case 17 developed a cardiomyopathy at one year of age, which caused recurrent dysrhythmias and cardiopulmonary arrests leading to his death at two years. OB was associated with patchy acute and organizing bronchopneumonia, alveolar wall necrosis and scattered foamy macrophages suggestive of aspiration. Pneumocystis carinii was found in association with OB in case 19. DISCUSSION

Obliterative bronchiolitis is an infrequent condition at any age. The last attempt to determine prevalence figures by review of autopsy data revealed one case in 42,038 autopsies of adults. 10 In our series, excluding patients known to have cystic fibrosis or bronchopulmonary dysplasia, seven cases were found after review of 2,987 pediatric autopsies spanning a 25-year inter484

val. Twelve additional cases were diagnosed at the Pulmonary Center over the same time period. OB is an unusual consequence of airway epithelial injury, but may be more common than previously thought. Like other uncommon medical problems, one must suspect OB in order to diagnose it. Greater awareness of this condition in our institution is reflected in the increased number of cases diagnosed since the mid 1970s, compared to the preceding 15 years, and the shorter period of time elapsed from onset of symptoms until diagnosis. The pathogenesis of OB includes airway epithelial injury with subsequent intraluminal scarring rather than normal repair. Current descriptions of the pathologic changes can include the involvement of peripheral bronchi as well as bronchioles, II concentric scarring causing the constrictive form of OB,12 and organizing pneumonia with airspace involvement. 13 Obstruction leads to the absorption of air, lung collapse, stagnation of secretions, inflammation, bronchiectasis, and fibrosis. II Hyperlucent lung syndrome is caused by air trapping with secondary decreases in pulmonary blood flow and gradual atrophy of the involved portion of lung tissue. 3.4.14 Initial reports described adults with OB following toxic fume inhalation.P'" Many diverse injuries have now been associated with the development of OB and are summarized in Table 5. Aspiration of food and stomach contents also may playa significant role in the development of OB. This 'possibility was first mentioned by Wegelin , 17 who described OB in a patient after aspiration of a prune pit. In 1969, McNamara described an adult with progressive respiratory insuffiObliterative Bronchiolitis in Children (Hardy, Schldlow, Zaerf)

Table 5-ContliOOna Aaocialetl with the Development of Obliterative Broraclaiolitit Inhalation of ToxinslFumes Ammonia chlorine Chloropierin (trichloronitromethane) Hydrochloric acid Mustard gas (dichloroethyl sulfide) Nitric acid Nitrogen dioxide (silo fillers disease) Phosgene (carbonyl chloride) Sulfuric acid Talcum powder Thermal injury Zinc chloride Infection

Viral

Adenovirus (types 1, 3, 7, 21) Influenza Measles variable-zoster Bacterial

Bordetella pertuuis Staphylococcus tJU~

Streptococcus Group B beta hemolytic Other Mycoplasma pneumonia Pneumocystis Connective Tissue Diseaseffransplantation Autoimmune hemolytic anemia Bone marrow transplantation Eosinophilic fasciitis Heart-lung transplantation Rheumatoid arthritis Scleroderma Sjogren s syndrome Large Lesions Alveolar proteinosis Bronchopulmonary dysplasia Congenital Congestive heart f8ilure Cystic fibrosis Lymphoma Myasthenia gravis Penicillamine therapy-rheumatoid arthritis SulfasaJazjne therapy-ulcerative colitis Aspiration Foreign bodies (prune pit, amniotic fluid) Lipids (poppyseed oil) Stomach contents-gastroesophageal reflux Idiopathic

ciency and OB who seemingly had GER.18 This association has not been emphasized previously in the pediatric literature. Experimental bronchiolar obliteration has been produced in dogs following direct instillation of hydrochloric acid into the trachea. 19 Four children in our series had GER and aspiration and two others probably hadunrecognized recurrent aspiration of food. These examples suggest a cause-effect relationship between aspiration and OB in these patients. When OB is considered, a ventilation/perfusion scan should be obtained to look for matched areas of absent or decreased air and blood flO\\'. This study shows a mottled distribution of defects in stark contrast to the

paucity of abnormalities seen on the plain film.10 Rigid bronchoscopy is not helpful in making the diagnosis since the pathology is distal to the examined airways. Further clarification is obtained by bronchography. The technique utilized at SCHC of positive pressure breaths in the anesthetized patient minimized filling defects due to mucous impaction which is associated with filling of the mucous crypts and round convex filling defects not found in our patients. Il.II The characteristic pruned-tree appearance discussed above is typical of the disease and makes this condition one of few in which bronchography is useful in children. Computerized tomography does not provide adequate resolution fur definitive diagnosis of bronchiectasis in peripheral airways of small infants, but is a noninvasive diagnostic test for bronchiectasis being investigated in the older child. 13 Lung biopsy, helpful if the diagnosis is found, is an invasive procedure that does not always confirm the diagnosis because of the patchy distribution of airway involvement. In situations where the sample contains fewifany bronchioles, focal emphysema suggests more proximal airway obstruction and air trapping through collateral ventilation." If patchy areas of interstitial fibrosis and organizing pneumonia are present, a careful examination of the airways for obliteration is needed. 13 In some cases, tissue destruction is so severe that bronchioles may not be readily recognizable, and elastic stains may reveal remnants of airway walls." During the acute phase, airway damage and necrosis set the stage for OB, but scarring may not be present. A biopsy this early in the course of the cicatricial process may show bronchiolar necrosis and plugging with minimal fibroblastic response. Not all of our group 1 patients were categorized by a typical biopsy specimen. We now believe, like others,18.JC that the diagnosis of OB in children can be based on the characteristic clinical situation, pulmonary function abnormalities, ventilation-perfusion scan and bronchographic changes without need for open lung biopsy. Use of corticosteroid therapy in the early phase of illness in an attempt to modify the fibroblastic response is based on the work of Moran. 15 The administration of steroid and antibiotic therapy to rabbits one day before intratracheal instillation of nitric acid prevented OB in all but one of the surviving animals, although more than two-thirds of the original group died of pulmonary edema and pneumonia. This contrasted with the development of OB in 50 percent of the surviving rabbits who were not pretreated. Because OB is an infrequent condition in children, no controlled study of the effect of steroid therapy has been possible. No observable improvement in the rate of recovery or ultimate outcome was obvious in our patients following steroid treatment, although the numbers are small and this therapy may have been initiated after SignificantfibroCHEST I 93 I 3 I MARCH, 1988

485

sis had already occurred. Other investigators have reported variable efficacy of corticosteroid therapy in adult patients with OB.l3 Resection of involved segments in selected patients who develop bronchiectasis may be helpful to treat recurrent infection. The course of patients with OB varies from mild, asthma-like symptoms to rapidly progressive deterioration and death. Survival with airway obstruction and air trapping, occasionally bronchodilator-responsive, was the most common outcome in our patients. Recanalization of partially occluded airways may occur in some and contribute to their apparent improvement of symptoms. Obliterative bronchiolitis is an uncommon yet potentially severe process following acute lower airway injury in children. It is possible that, in many children, the diagnosis ofOB is missed. OB should be suspected in the following instances: 1) persistent cough or wheezing after acute pneumonia; 2) prolonged localized crackles or wheezing after severe acute respiratory failure; 3) prolonged exercise intolerance following an acute pulmonary injury; 4) respiratory symptoms which are severe in disproportion to the paucity of plain chest radiographic findings; 5) recurrent aspiration of gastric contents, 6) hyperlucent lung syndrome, which may develop as soon as six weeks after acute pneumonia; or 7) severe lung disease with overinHation,often localized, with difficulty in ventilation and sluggish or absent recovery. Diagnostic studies should include ventilation-perfusion scans, bronchography and lung biopsy when necessary. Recognition and supportive treatment during the acute and chronic phases may improve the functional status of these patients. t

•

ACKNOWLEDGMENTS: The authors gratefully acknowledge the assistance of Dr. Barbara Wolfson fur her review of the radiologic materials presented. Permission fur the publication of information about patients previously published in part was granted by Drs. Lourdes Cuasay, Judy Palmer and Marie Capitanio. Dr. Hardy was a research fellow of the American Lung Association.

REFERENCES 1 Gosink BB, Friedman PJ, Liebow AA. Bronchiolitis obliterans: roentgenologic-pathologic correlation. AJR 1973; 117:816-32 2 Culiner MM. Obliterative bronchitis and bronchiolitis with bronchiectasis. Dis Chest 1963; 44:351-61 3 1lltochenko ~ Rachinsky S, Spichak 1: Kudratova M. Chronic obstructive pulmonary disease as sequelae of bronchiolitis obliterans. Progr Respir Res 1981; 238-43 4 Swyer PR, James GCW A case of unilateral pulmonary emphysema. Thorax 1953; 8:133-36 5 Becroft D MO. Bronchiolitis obliterans, bronchiectasis, and other sequelae of adenovirus type 21 infection in young children.

J Clio Pathol 1971; 24:72-82 6 Benyesh-Melnick M, Rosenberg HS. The isolation of adenovirus type 7 from a fatal case of pneumonia and disseminated disease. J Pediatr 1964; 64:83-86 7 Wenman WM, Pagtakhan RD, Reed MH, Chernick ~ Albritton W. Adenovirus bronchiolitis in Manitoba. 1982; 5:605-09 8 Laraya-Cuasay LR, DeForest A, Huff D, Lischner H, Huang NH. Chronic pulmonary complications of early influenza virus infection in children. Am Rev Respir Dis 1977; 16:617-25 9 Blumgart HL, MacMahon HE. Bronchiolitis fibrosa obliterans: a clinical and pathologic study. Med Clio North Am 1929; 13: 197-214 10 LaDue JS. Bronchiolitis fibrosa obliterans. Arch Intern Med 1941; 68:663-73 11 Aziairad H, Polgar G, Borns PF, Chatten J. Bronchiolitis obliterans. Clio Pediatr 1975; 14:572-84 12 Katzenstein AL, Askin FB. Miscellaneous I. Specific diseases of uncertain etiology. In: Bennington JL, edt Surgical pathology of non neoplastic lung disease. Philadelphia: WB Saunders, 1982; 349-56 13 Epler GR, Colby rv McLoud TC, Carrington CB, Gaensler EA. Bronchiolitis obliterans organizing pneumonia. N Eng} J Med 1985; 312:152-58 14 Macpherson RI, Cumming GR, Chernick ~ Unilateral hyperlucent lung: a complication of viral pneumonia. J Can Assoc Radiologists 1969; 20:225-31 15 Lange W. Ueber eine eigentumliche erkrankung der kleinen bronchien und bronchiolen (bronchitis et bronchiolitis obliterans). Deutsch Arch lOin Med 1901; 70:342-64 16 Fraenkel A. Ueber bronchiolitis fibrosa obliterans, nebst bemerkungen uber lungenhypereamie und inderierende pneumonia. Deutsch Arch lOin Med 1902; 73:484-88 17 Wegelio C. Ueber bronchitis obliterans nach fremdkorperaspiration. Beitr Pathol Anat 1908; 43:438-54 18 McNamara JJ, Urschel HC, Arndt JH, Ulevitch H, Kingsley WB. Idiopathic unilateral hyperlucent lung, the Swyer James syndrome. Ann Thorac Surg 1969; 7:351-56 19 Moran TJ. Experimental aspiration pneumonia ~ Inflammatory and reparative changes produced by intratracheal injections of autologous gastric juice and hydrochloric acid. Arch Patholl955; 60:122-29 20 Palmer J, Harcke 1: Deforest A, Schidlow D, Cuasay L, Huang N. Matched ventilation/perfusion defects in the lung scans of children with obliterative bronchiolitis and long term clinical fullowup. Am Rev Respir Dis 1979; 119:280 21 Simon G, Galbraith HJ. Radiology of chronic bronchitis. Lancet 1953; 2:850-52 22 Gregg I, 'Irapnell DM. The bronchographic appearances of early chronic bronchitis. Br J Radioll969; 42:132-39 23 Nadich D~ McCauley DI, Khouri NR Computed tomography of bronchiectasis. J Comp Assist Tomo 1982; 6:437-44 24 Isles AF, Masel J, O'Dulfy J. Obliterative bronchiolitis due to Mycoplasma pneumoniae infection in a child. Ped Radioll987; 17:109-11 25 Moran TJ, Hellstrom NR: Bronchiolitis obliterans. Arch Pathol 1958; 66:691-707 26 Katzenstein AL, Myers J, Prophet WD, Corley LS, Shin MS: Bronchiolitis obliterans and usual interstitial pneumonia, a comparative clinicopathologic study. Am J Surg Pathol 1986; 10(6):373-381

Obliterative Bronchiolitis In Children (Hardy, Seh/d/OW, z.rt)