LUNG
A case of severe, probably viral pneumonitis in a three-year-old child is presented, which resulted in complete atelectasis of the left lung, and in diffuse changes of bronchiolitis and bronchitis obliterans. The case represents a variant of bronchiolitis obliterans.
THE
CLASSIC bronchiolitis obliterans, a disease in man, was first described by Lange in 1901.~ LaDuel found one case in 42,038 consecutive necropsies covering a 42-year period. It is essentially a disease of young adults, but a few instances have been reported in small children. 3,4 The youngest was a premature of 1,430 gm5 in whom the disorder was seemingly congenital. No predilection exists for sex or geographic area. Our case has some unusual features. rare
Bronchiolitis
Obliterans
Case
Hassan Azizirad, M.D.,*
three-year old Puerto Rican boy was transferred from another hospital to The Children’s Hospital of Philadelphia on February 23, 1972 for evaluation of his pulmonary disease. For two weeks he had had coughing and diarrhea. In the past, he had had repeated pulmonary infections. On admission, he was in respiratory distress and was slightly cyanotic. He had prolonged expirations with a few rhonchi and bilateral moist rales in both lung fields. Chest x-ray was interpreted as bilateral pneumonia (Fig. I). He was placed in an oxygen tent and treated first with ampicillin and then with methicillin. After the sixth day of hospitalization he became afebrile. Repeat chest film two weeks later revealed resolving pneumonia (Fig. 2). The following tests were reported as negative: sweat test, febrile and cold agglutinins, blood culture, gastric washing for acid-fast bacilli, ova and parasites in the stool, tuberculin skin test, and cerebrospinal fluid (CSF) tests. In the culture from the throat, E. call and Monilia were observed. Serum protein electrophoresis was within normal limits. On second admission, the patient was alert, afebrile, and in no acute distress. Scattered expiratory wheezes and rales were audible in both
Report
A
George Polgar, M.D., Patricia F. Borns, M.D., Jane Chatten, M.D.
From the Division of Respiratory Diseases, and Departments of Radiology and Pathologic Anatomy, the Children’s Hospital of Philadelphia, 34th and Civic Center Boulevard, Philadelphia, Pa. 19104. Correspondence to Hassan Azizirad, % Dr. George Polgar, Respiratory Diseases, Children’s Hospital of Michigan, 3901 Beaubien, Detroit, Michigan
48201
572
Downloaded from cpj.sagepub.com at OAKLAND UNIV on June 7, 2015
I
Radiogram taken January 13, 1972. Bi-
FiG. 1. on
lateral basilar infiltrates most marked on the left. The changes are those of acute
inflammation.
lung
from the clinical
murmurs were
was
bases. Heart sound were normal and no heard. The liver edge was 6 cm below the right costal margin. The remainder of the physical examination was essentially normal. Laboratory studies showed a blood count as follows: white blood cells, 14,700, 52 per cent polymorphonuclears, 37 per cent lymphs, 7 per cent monocytes, 2 per cent eosinophils. The total
eosinophil g/100 ml;
count was
535/mm~, hemoglobin 13.7
and platelet count 380,000. The sedimentation rate was not elevated. Liver function tests were normal, the tuberculin test was negative, and a culture of tracheal aspirate showed no growth. Repeat chest x-ray and bronchogram are shown in Figures 3 and 4. The possibility of bronchiolitis obliterans, suggested
course
and routine chest films,
supported by the bronchogram. The patient was discharged on March 6 with the diagnosis of resolving bronchopneumonia, probably viral, to be followed in the clinic. In repeated clinic visits, he appeared to be in good general condition, but auscultatory findings
coarse rales and later bronchovesicular sounds on the left) persisted. Two months after discharge, the chest x-ray revealed the collapse of the entire left lung (Fig. 5). On June 5, a lung biopsy was performed. Small bronchi exhibited patchy replacement of the epithelium and lumina by granulation tissue. Most of the bronchi had some degree of peribronchial cellular infiltrate.
(rhonchi,
573
Downloaded from cpj.sagepub.com at OAKLAND UNIV on June 7, 2015
FIG. 2. on
Radiogram taken
January 28, 1972.
of previous basilar consolidation. The chest film could easily be read as normal. There is an increase in the interstitial markings which might be read as a miliary pattern, and the left lung may be slightly smaller than the
Clearing
right.
One month later, the patient had an episode of fever with respiratory distress and was treated with antibiotics. Cough, shortness of breath, and easy fatiguibility persisted. A lung scan on June 30 showed marked underperfusion of the left lung. A left pneumonectomy was performed on August 18 with an uneventful
high
postoperative
course.
The resected lung had the wrinkled pleural surface of atelectasis and a nodular consistency throughout. The cut surface was studded with white, tough circular and oval patches, occasionally with pinpoint central lumina (Fig. 6). The main bronchi were normal in caliber and filled with mucoid exudate. The smaller bronchi tapered until the lumina were not detectable beyond the third or fourth branching. Microscopx
ically, the large bronchi exhibited chronic inflammatory thickening of their walls (with polypoid tufts of granulation tissue in some), muscular hyperplasia, and peribronchial lymphoid hyperplasia. The smaller bronchi were recognized as spheres of acellular granulation tissue and fibrous tissue surrounded by muscularis and an occasional cartilage (Fig. 7). There was mild sclerosis of the large arteries. Atelectasis was the only parenchymal change. The patient was lost to follow-up for about five months, during which time he was hospitalized elsewhere for an acute respiratory infection and treated with antibiotics. When seen again, he had a cough, occasional rhonchi, and rales over the right lower lobe. Chest x-ray showed inflammatory changes in the right lower lobe. He re-
574
Downloaded from cpj.sagepub.com at OAKLAND UNIV on June 7, 2015
FIG. 3.
Radiogram taken
February 23, 19’l~. Progressive loss of volume of the left lung. There is overexpansion of the right lung on
with persistent increase in the interstitial markings. The left lung shows thickening of the bronchial walls but the periphery of the lung is still aerated.
to antibiotics but there was some residual involvement in that area. He had a moderate degree of scoliosis as a consequence of the
sponded
pneumonectomy. ~
Discussion The causes of bronchiolitis obliterans, as summarized from the literature, can be divided into three groups. 1. Inhalation of Irritant Substances. Examples are fumes of oxides of nitrogen,’ especially nitric acid (white fuming and red fuming) used in certain industries and as oxidizers in rocket fuel, and the fumes of
sulfuric acid, concentrated ammonia and of burning x-ray film.8 Muntsch9 mentions the disease as the result of World War I gas poisoning. Winternitz’O produced the disease experimentally by exposing the dogs to chlorine, phosgene, chloropicrine, and other war
gases. 2. Infections. Bronchiolitis obliterans has been reported following tuberculosis, whooping cough, and infections with viruses, such as measles, influenza, and adenoviruses.3,1l-13 3. Various Other Causes. Aspiration of amniotic fluid, Lipiodol, or foreign bodies have also been suggested.~3
575
Downloaded from cpj.sagepub.com at OAKLAND UNIV on June 7, 2015
-
The clinical picture is variable, depending in part upon the etiology. Usually three stages can be identified. 1. Early Stage. This is typically an acute and febrile period with cough as the major
symptom. Respiratory distress, cyanosis and chest pain are common, and more severe after the inhalation of an irritant substance. This stage does not extend beyond two weeks. 2. Stage of Remission. This is an interval of apparent improvement, when subjective symptoms, temperature, and some of the physical and radiologic findings subside.
&dquo;
_
FIG. 4. Bronchogram taken on February 28, 1972. The bronchial dilatations on the left end abruptly. The appearance is not that seen with classical bronchiectasis, caused by destruction of bronchial walls, but rather the &dquo;broken bough&dquo; appearwith ance described bronchiolar obstruction.
Considerable expectoration is seen in adults. This phase may last from one to two months. 3. Stage of Progression. This stage is characterized by severe dyspnea with increasing cough, expectoration, and occasional bloodstreaked sputum. Cyanosis is usually present. Death may occur in one to two months. The radiologic picture may resemble miliary tuberculosis, or show pneumonic infiltrates, or hyperaeration and other nonspecific changes. In the bronchogram, the contrast material does not reach the peripheral, smaller bronchi (&dquo;broken bough&dquo; appearance). Pathologically, typically the bron-
576
Downloaded from cpj.sagepub.com at OAKLAND UNIV on June 7, 2015
FIG. 5.
Radiogram taken May 16, 1972. The left lung is now small, opaque,
on
and demonstrates
an
ex-
tensive air bronchogram. The interstitial densities in the overexpanded right lung are unchanged and there is a relatively radiolucent area in the right mid-lung. The process is
.
stationary when compared with subsequent examinations.
chioles and occasionally some small bronchi are involved. The lesion appears as multiple .-
greyish-white nodules, 1-2 mm in resembling’ miliary tuberculosis,
diameter, but
the
nodules are whiter, much firmer and free of caseation. The nodules are irregular because of bronchial infiltration and fibrosis. A tiny pore may be seen in the nodule which is the lumen of the occluded bronchiole. Micro-’ scopically, the pathologic process is seen to involve the bronchiolar lumen and the surrounding tissues. Coexistence of lesions in different stages of development demonstrate the sequence of the lesions. Initially, cellular
granulation tissue more or less fills the lumen of bronchioles. This tissue then undergoes organization and takes a polypoid form. The final fibrosis extends to the musculoelastic and peribronchial tissue. In the advanced stage, one can see bronchioles with a fibrous wall and a deformed and eccentric lumen in the shape of a cresent. Eventually, only star-shaped fibrous cicatrices will be seen. The lung may become either emphysematous or atelectatic, depending upon the partial or complete obliteration of the bronchioles. (Continued on page 582)
577
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delays fibrosis in rabbits much more effectively than in the guinea pig, monkey, tisone
or man.
FIG. 6. Cut surface of resected outlines bronchial walls and
lung
while fibrous tissue their lumen.
narrows
(Continued from page 577) Differential diagnosis includes such abnormalities as bronchial asthma (especially in
wheezing), cystic fibrosis, viral infection, tuberculosis, Pneumocytis carinii pneumonia, alveolar proteinosis, desquamative interstitial pneumonia, and pulmonary
children with
fibrosis. Treatment may include steroids in the early stage of the disease especially when exposure to an irritant substance is known. In a study by Moran et al.,14 the changes from intratracheal injection of nitric acid in rabbits was prevented in all but one of the 12 surviving animals (more than two-thirds of them died of pulmonary edema and pneumonia) by giving steroid and antibiotics one day prior to exposure. In rabbits not treated, 50 per cent of the survivors exhibited the disease. These results are not directly applicable to humans because cor-_._-_._._--_._-~._--
FIG. 7.
---
The case presented here appears to be a variant of the classic bronchiolitis obliterans. The first two stages of the disease observed in our patient were in accord with the classic description, showing an initial period of respiratory distress, then clinical improvement with normal chest radiograms. However, the third stage which is usually a period of severe and often fatal respiratory distress was here prolonged, with periods of remission and exacerbation and eventually a complete collapse of the left lung, which failed to re-expand. The pathologic lesions were more widespread than usual. Obliterative lesions were seen not only in bronchioles but also in larger bronchi. It is probably because of the diffuse airway obstruction in this case that no hyperaeration in the periphery of the lung developed, as observed in most of the reported cases in children. A similar explanation was given for this finding in an epidemic of adenovirus Type 21 infection studied by Becroft. 13 There is evidence that patients who rethis disease later develop a cover from condition called Swyer-James, McLeod, or unilateral hyperlucent lung syndrome. 15,16 Reid and Simon17 in 1962 reviewed the bronchograms in several published cases with this syndrome, and in 12 of their own cases. In none did bronchial filling extend to the periphery. In nine of their 12 cases, they observed a mixture of &dquo;broken bough&dquo; appearance and distortion, and, in three, irregularities of all endings were noted. The same authors by examining four specimens excised from adults with Swyer-James syndrome, concluded that the essential lesions seem to be multiple bronchial or bronchiolar obliterations. It must be obvious from these observations that bronchiolitis obliterans can have a vary-ing course and the final radiologic and pathologic appearance of the lung may also ). _
Photomicrographs of obliterated small bronchi. These can be recognized as granulation tissue. a) longitudinal section x 21 tl9 b) crossection
582
Downloaded from cpj.sagepub.com at OAKLAND UNIV on June 7, 2015
muscle x 130.
coats
surrounding
Downloaded from cpj.sagepub.com at OAKLAND UNIV on June 7, 2015
6.
be quite different. In some cases, the disease may develop into the hyperlucent lung syndrome, in others irreversible atelectasis or bronchiectasis may result, and perhaps in some there is no permanent residue at all. The reason for the variability of the disease is probably related to the etiology, to the extent of initial lung damage, to the effect of repeated infections, and to the range of reparative processes following the insult. While preparing this article we have encountered the disease in one other child, and suspected it in two others with adenovirus type 7 pneumonia.
7. Edens: Uber bronchiolitis obliterans. Dtsch. Arch. Klin. Med. 85: 598, 1906. 8. The hazard of toxic gases from combustion roentgen-ray films. JAMA 92: 1764, 1929. 9. Muntsch, O.: Leitfaden der Pathologie und Therapie der Kampfstofferkrankungen, 4th ed. Leipzig, VEB Georg Thieme, 1936. 10. Winternitz, M. C.: Collected Studies on Pathology of War Gas Poisoning. New Haven, Yale University Press, 1920, p. 24. 11. Baar, H. S., and Galindo, J.: Bronchiolitis obliterans. Thorax 21: 209, 1966. 12. Lang, W. R., Howden, C. W., Laws, J., and Burton, J. F.: Bronchopneumonia with serious sequelae in children with evidence of adenovirus type 21 infection. Br. Med. J. 1: 73, 1969. 13. Becroft, D. M. O.: Bronchiolitis obliterans, bronchiectasis, and other sequelae of adenovirus type 21 infection in young children. J. Clin. Pathol.
References 1.
2. 3.
4. 5.
24: 72, 1971. 14. Moran, T. J., and Hellstrom, R.: Bronchiolitis obliterans. Arch. Pathol. 66: 691, 1958. 15. Cumming, G. R., Macpherson, R. I., and Chernick, V.: Unilateral hyperlucent lung syndrome in
W.: Uber eine eigentumliche erkrankung der kleinen bronchien und bronchiolen. Dtsch. Arch. Klin. Med. 70: 342, 1901. LaDue, J.: Bronchiolitis fibrosa obliterans. Arch. Intern. Med. 68: 663, 1941. : La bronchiolite et al. Despres, P., Allaneau, C., obliterante du nourrisson. Ann. Pediatr. (Paris) 18: 667, 1971. : La bronchiolite Nezelof, C., Meyer, B., et al. obliterante. Ann. Pediatr. (Paris) 17: 534, 1970. Laurent, M., Dalloz, J. C., and Nezelof, C.: La bronchiolite obliterante. Arch. Anat. Pathol. (Paris) 14: 253, 1966.
Lange,
16.
children. J. Pediatr. 78: 250, 1971. Marvin, S., Kogutt, L. E., Swischuk, L. E., and Goldblum, R.: Swyer-James syndrome (unilateral hyperlucent
lung)
in children. Am.
J.
Dis. Child. 125:
614, 1973. 17. Reid, L., and Simon, G.: Unilateral lung traradiancy. Thorax 17: 230, 1962. 18. Reid, L., and Simon, G.: The role of alveolar hypoplasia in some types of emphysema. Br. J. Chest 58: 158, 1964.
From January I to May 7, 1974, total of 76,383 cases of smallpox were reported to WHO. This is an increase of 34 per cent over the number of cases recorded during the same period in 1973. Part of the increase may be attributed to a more effective surveillance system throughout much of India and Pakistan, with the result that the reporting of cases is now virtually complete. At the same time, however, explosive epidemics have developed in the Indian State of Bihar and in adjacent states. The State of Bihar alone accounted for more than half of the world’s total of cases in 1974 up to May 7, and India for more than 80 per cent of all cases. In all four countries where smallpox is still endemic (Bangladesh, Ethiopia, India, and Pakistan), the areas affected have a
World Progress in the Eradication of Smallpox
McAdams, A. J., Jr.: Bronchiolitis obliterans. Am. J. 19: 314, 1955. Med.
_
diminished. More than 90 of all the smallpox cases reported occurred in areas comprising less than 15 per cent of the total land area of the four contries. This decrease in the extent of smallpox endemic areas continues a steady trend that started in 1967 when, at the outset of the program, 30 countries were considered to be endemic. For epidemiologic and operational purposes, these countries were grouped into four regions: South America, Indonesia, mainland Asia, and Africa. Smallpox is deemed to have been eradicated after at least two years have elapsed since the last detected cases, the surveillance measures being considered sufficent to detect any cases during that time. (Continued on page 591)
steadily per
cent
584
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A case of severe, probably viral pneumonitis in a three-year-old child is presented, which resulted in complete atelectasis of the left lung, and in diffuse changes of bronchiolitis and bronchitis obliterans. The case represents a variant of bronchiolitis obliterans.
THE
CLASSIC bronchiolitis obliterans, a disease in man, was first described by Lange in 1901.~ LaDuel found one case in 42,038 consecutive necropsies covering a 42-year period. It is essentially a disease of young adults, but a few instances have been reported in small children. 3,4 The youngest was a premature of 1,430 gm5 in whom the disorder was seemingly congenital. No predilection exists for sex or geographic area. Our case has some unusual features. rare
Bronchiolitis
Obliterans
Case
Hassan Azizirad, M.D.,*
three-year old Puerto Rican boy was transferred from another hospital to The Children’s Hospital of Philadelphia on February 23, 1972 for evaluation of his pulmonary disease. For two weeks he had had coughing and diarrhea. In the past, he had had repeated pulmonary infections. On admission, he was in respiratory distress and was slightly cyanotic. He had prolonged expirations with a few rhonchi and bilateral moist rales in both lung fields. Chest x-ray was interpreted as bilateral pneumonia (Fig. I). He was placed in an oxygen tent and treated first with ampicillin and then with methicillin. After the sixth day of hospitalization he became afebrile. Repeat chest film two weeks later revealed resolving pneumonia (Fig. 2). The following tests were reported as negative: sweat test, febrile and cold agglutinins, blood culture, gastric washing for acid-fast bacilli, ova and parasites in the stool, tuberculin skin test, and cerebrospinal fluid (CSF) tests. In the culture from the throat, E. call and Monilia were observed. Serum protein electrophoresis was within normal limits. On second admission, the patient was alert, afebrile, and in no acute distress. Scattered expiratory wheezes and rales were audible in both
Report
A
George Polgar, M.D., Patricia F. Borns, M.D., Jane Chatten, M.D.
From the Division of Respiratory Diseases, and Departments of Radiology and Pathologic Anatomy, the Children’s Hospital of Philadelphia, 34th and Civic Center Boulevard, Philadelphia, Pa. 19104. Correspondence to Hassan Azizirad, % Dr. George Polgar, Respiratory Diseases, Children’s Hospital of Michigan, 3901 Beaubien, Detroit, Michigan
48201
572
Downloaded from cpj.sagepub.com at OAKLAND UNIV on June 7, 2015
I
Radiogram taken January 13, 1972. Bi-
FiG. 1. on
lateral basilar infiltrates most marked on the left. The changes are those of acute
inflammation.
lung
from the clinical
murmurs were
was
bases. Heart sound were normal and no heard. The liver edge was 6 cm below the right costal margin. The remainder of the physical examination was essentially normal. Laboratory studies showed a blood count as follows: white blood cells, 14,700, 52 per cent polymorphonuclears, 37 per cent lymphs, 7 per cent monocytes, 2 per cent eosinophils. The total
eosinophil g/100 ml;
count was
535/mm~, hemoglobin 13.7
and platelet count 380,000. The sedimentation rate was not elevated. Liver function tests were normal, the tuberculin test was negative, and a culture of tracheal aspirate showed no growth. Repeat chest x-ray and bronchogram are shown in Figures 3 and 4. The possibility of bronchiolitis obliterans, suggested
course
and routine chest films,
supported by the bronchogram. The patient was discharged on March 6 with the diagnosis of resolving bronchopneumonia, probably viral, to be followed in the clinic. In repeated clinic visits, he appeared to be in good general condition, but auscultatory findings
coarse rales and later bronchovesicular sounds on the left) persisted. Two months after discharge, the chest x-ray revealed the collapse of the entire left lung (Fig. 5). On June 5, a lung biopsy was performed. Small bronchi exhibited patchy replacement of the epithelium and lumina by granulation tissue. Most of the bronchi had some degree of peribronchial cellular infiltrate.
(rhonchi,
573
Downloaded from cpj.sagepub.com at OAKLAND UNIV on June 7, 2015
FIG. 2. on
Radiogram taken
January 28, 1972.
of previous basilar consolidation. The chest film could easily be read as normal. There is an increase in the interstitial markings which might be read as a miliary pattern, and the left lung may be slightly smaller than the
Clearing
right.
One month later, the patient had an episode of fever with respiratory distress and was treated with antibiotics. Cough, shortness of breath, and easy fatiguibility persisted. A lung scan on June 30 showed marked underperfusion of the left lung. A left pneumonectomy was performed on August 18 with an uneventful
high
postoperative
course.
The resected lung had the wrinkled pleural surface of atelectasis and a nodular consistency throughout. The cut surface was studded with white, tough circular and oval patches, occasionally with pinpoint central lumina (Fig. 6). The main bronchi were normal in caliber and filled with mucoid exudate. The smaller bronchi tapered until the lumina were not detectable beyond the third or fourth branching. Microscopx
ically, the large bronchi exhibited chronic inflammatory thickening of their walls (with polypoid tufts of granulation tissue in some), muscular hyperplasia, and peribronchial lymphoid hyperplasia. The smaller bronchi were recognized as spheres of acellular granulation tissue and fibrous tissue surrounded by muscularis and an occasional cartilage (Fig. 7). There was mild sclerosis of the large arteries. Atelectasis was the only parenchymal change. The patient was lost to follow-up for about five months, during which time he was hospitalized elsewhere for an acute respiratory infection and treated with antibiotics. When seen again, he had a cough, occasional rhonchi, and rales over the right lower lobe. Chest x-ray showed inflammatory changes in the right lower lobe. He re-
574
Downloaded from cpj.sagepub.com at OAKLAND UNIV on June 7, 2015
FIG. 3.
Radiogram taken
February 23, 19’l~. Progressive loss of volume of the left lung. There is overexpansion of the right lung on
with persistent increase in the interstitial markings. The left lung shows thickening of the bronchial walls but the periphery of the lung is still aerated.
to antibiotics but there was some residual involvement in that area. He had a moderate degree of scoliosis as a consequence of the
sponded
pneumonectomy. ~
Discussion The causes of bronchiolitis obliterans, as summarized from the literature, can be divided into three groups. 1. Inhalation of Irritant Substances. Examples are fumes of oxides of nitrogen,’ especially nitric acid (white fuming and red fuming) used in certain industries and as oxidizers in rocket fuel, and the fumes of
sulfuric acid, concentrated ammonia and of burning x-ray film.8 Muntsch9 mentions the disease as the result of World War I gas poisoning. Winternitz’O produced the disease experimentally by exposing the dogs to chlorine, phosgene, chloropicrine, and other war
gases. 2. Infections. Bronchiolitis obliterans has been reported following tuberculosis, whooping cough, and infections with viruses, such as measles, influenza, and adenoviruses.3,1l-13 3. Various Other Causes. Aspiration of amniotic fluid, Lipiodol, or foreign bodies have also been suggested.~3
575
Downloaded from cpj.sagepub.com at OAKLAND UNIV on June 7, 2015
-
The clinical picture is variable, depending in part upon the etiology. Usually three stages can be identified. 1. Early Stage. This is typically an acute and febrile period with cough as the major
symptom. Respiratory distress, cyanosis and chest pain are common, and more severe after the inhalation of an irritant substance. This stage does not extend beyond two weeks. 2. Stage of Remission. This is an interval of apparent improvement, when subjective symptoms, temperature, and some of the physical and radiologic findings subside.
&dquo;
_
FIG. 4. Bronchogram taken on February 28, 1972. The bronchial dilatations on the left end abruptly. The appearance is not that seen with classical bronchiectasis, caused by destruction of bronchial walls, but rather the &dquo;broken bough&dquo; appearwith ance described bronchiolar obstruction.
Considerable expectoration is seen in adults. This phase may last from one to two months. 3. Stage of Progression. This stage is characterized by severe dyspnea with increasing cough, expectoration, and occasional bloodstreaked sputum. Cyanosis is usually present. Death may occur in one to two months. The radiologic picture may resemble miliary tuberculosis, or show pneumonic infiltrates, or hyperaeration and other nonspecific changes. In the bronchogram, the contrast material does not reach the peripheral, smaller bronchi (&dquo;broken bough&dquo; appearance). Pathologically, typically the bron-
576
Downloaded from cpj.sagepub.com at OAKLAND UNIV on June 7, 2015
FIG. 5.
Radiogram taken May 16, 1972. The left lung is now small, opaque,
on
and demonstrates
an
ex-
tensive air bronchogram. The interstitial densities in the overexpanded right lung are unchanged and there is a relatively radiolucent area in the right mid-lung. The process is
.
stationary when compared with subsequent examinations.
chioles and occasionally some small bronchi are involved. The lesion appears as multiple .-
greyish-white nodules, 1-2 mm in resembling’ miliary tuberculosis,
diameter, but
the
nodules are whiter, much firmer and free of caseation. The nodules are irregular because of bronchial infiltration and fibrosis. A tiny pore may be seen in the nodule which is the lumen of the occluded bronchiole. Micro-’ scopically, the pathologic process is seen to involve the bronchiolar lumen and the surrounding tissues. Coexistence of lesions in different stages of development demonstrate the sequence of the lesions. Initially, cellular
granulation tissue more or less fills the lumen of bronchioles. This tissue then undergoes organization and takes a polypoid form. The final fibrosis extends to the musculoelastic and peribronchial tissue. In the advanced stage, one can see bronchioles with a fibrous wall and a deformed and eccentric lumen in the shape of a cresent. Eventually, only star-shaped fibrous cicatrices will be seen. The lung may become either emphysematous or atelectatic, depending upon the partial or complete obliteration of the bronchioles. (Continued on page 582)
577
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Downloaded from cpj.sagepub.com at OAKLAND UNIV on June 7, 2015
Downloaded from cpj.sagepub.com at OAKLAND UNIV on June 7, 2015
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delays fibrosis in rabbits much more effectively than in the guinea pig, monkey, tisone
or man.
FIG. 6. Cut surface of resected outlines bronchial walls and
lung
while fibrous tissue their lumen.
narrows
(Continued from page 577) Differential diagnosis includes such abnormalities as bronchial asthma (especially in
wheezing), cystic fibrosis, viral infection, tuberculosis, Pneumocytis carinii pneumonia, alveolar proteinosis, desquamative interstitial pneumonia, and pulmonary
children with
fibrosis. Treatment may include steroids in the early stage of the disease especially when exposure to an irritant substance is known. In a study by Moran et al.,14 the changes from intratracheal injection of nitric acid in rabbits was prevented in all but one of the 12 surviving animals (more than two-thirds of them died of pulmonary edema and pneumonia) by giving steroid and antibiotics one day prior to exposure. In rabbits not treated, 50 per cent of the survivors exhibited the disease. These results are not directly applicable to humans because cor-_._-_._._--_._-~._--
FIG. 7.
---
The case presented here appears to be a variant of the classic bronchiolitis obliterans. The first two stages of the disease observed in our patient were in accord with the classic description, showing an initial period of respiratory distress, then clinical improvement with normal chest radiograms. However, the third stage which is usually a period of severe and often fatal respiratory distress was here prolonged, with periods of remission and exacerbation and eventually a complete collapse of the left lung, which failed to re-expand. The pathologic lesions were more widespread than usual. Obliterative lesions were seen not only in bronchioles but also in larger bronchi. It is probably because of the diffuse airway obstruction in this case that no hyperaeration in the periphery of the lung developed, as observed in most of the reported cases in children. A similar explanation was given for this finding in an epidemic of adenovirus Type 21 infection studied by Becroft. 13 There is evidence that patients who rethis disease later develop a cover from condition called Swyer-James, McLeod, or unilateral hyperlucent lung syndrome. 15,16 Reid and Simon17 in 1962 reviewed the bronchograms in several published cases with this syndrome, and in 12 of their own cases. In none did bronchial filling extend to the periphery. In nine of their 12 cases, they observed a mixture of &dquo;broken bough&dquo; appearance and distortion, and, in three, irregularities of all endings were noted. The same authors by examining four specimens excised from adults with Swyer-James syndrome, concluded that the essential lesions seem to be multiple bronchial or bronchiolar obliterations. It must be obvious from these observations that bronchiolitis obliterans can have a vary-ing course and the final radiologic and pathologic appearance of the lung may also ). _
Photomicrographs of obliterated small bronchi. These can be recognized as granulation tissue. a) longitudinal section x 21 tl9 b) crossection
582
Downloaded from cpj.sagepub.com at OAKLAND UNIV on June 7, 2015
muscle x 130.
coats
surrounding
Downloaded from cpj.sagepub.com at OAKLAND UNIV on June 7, 2015
6.
be quite different. In some cases, the disease may develop into the hyperlucent lung syndrome, in others irreversible atelectasis or bronchiectasis may result, and perhaps in some there is no permanent residue at all. The reason for the variability of the disease is probably related to the etiology, to the extent of initial lung damage, to the effect of repeated infections, and to the range of reparative processes following the insult. While preparing this article we have encountered the disease in one other child, and suspected it in two others with adenovirus type 7 pneumonia.
7. Edens: Uber bronchiolitis obliterans. Dtsch. Arch. Klin. Med. 85: 598, 1906. 8. The hazard of toxic gases from combustion roentgen-ray films. JAMA 92: 1764, 1929. 9. Muntsch, O.: Leitfaden der Pathologie und Therapie der Kampfstofferkrankungen, 4th ed. Leipzig, VEB Georg Thieme, 1936. 10. Winternitz, M. C.: Collected Studies on Pathology of War Gas Poisoning. New Haven, Yale University Press, 1920, p. 24. 11. Baar, H. S., and Galindo, J.: Bronchiolitis obliterans. Thorax 21: 209, 1966. 12. Lang, W. R., Howden, C. W., Laws, J., and Burton, J. F.: Bronchopneumonia with serious sequelae in children with evidence of adenovirus type 21 infection. Br. Med. J. 1: 73, 1969. 13. Becroft, D. M. O.: Bronchiolitis obliterans, bronchiectasis, and other sequelae of adenovirus type 21 infection in young children. J. Clin. Pathol.
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24: 72, 1971. 14. Moran, T. J., and Hellstrom, R.: Bronchiolitis obliterans. Arch. Pathol. 66: 691, 1958. 15. Cumming, G. R., Macpherson, R. I., and Chernick, V.: Unilateral hyperlucent lung syndrome in
W.: Uber eine eigentumliche erkrankung der kleinen bronchien und bronchiolen. Dtsch. Arch. Klin. Med. 70: 342, 1901. LaDue, J.: Bronchiolitis fibrosa obliterans. Arch. Intern. Med. 68: 663, 1941. : La bronchiolite et al. Despres, P., Allaneau, C., obliterante du nourrisson. Ann. Pediatr. (Paris) 18: 667, 1971. : La bronchiolite Nezelof, C., Meyer, B., et al. obliterante. Ann. Pediatr. (Paris) 17: 534, 1970. Laurent, M., Dalloz, J. C., and Nezelof, C.: La bronchiolite obliterante. Arch. Anat. Pathol. (Paris) 14: 253, 1966.
Lange,
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children. J. Pediatr. 78: 250, 1971. Marvin, S., Kogutt, L. E., Swischuk, L. E., and Goldblum, R.: Swyer-James syndrome (unilateral hyperlucent
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614, 1973. 17. Reid, L., and Simon, G.: Unilateral lung traradiancy. Thorax 17: 230, 1962. 18. Reid, L., and Simon, G.: The role of alveolar hypoplasia in some types of emphysema. Br. J. Chest 58: 158, 1964.
From January I to May 7, 1974, total of 76,383 cases of smallpox were reported to WHO. This is an increase of 34 per cent over the number of cases recorded during the same period in 1973. Part of the increase may be attributed to a more effective surveillance system throughout much of India and Pakistan, with the result that the reporting of cases is now virtually complete. At the same time, however, explosive epidemics have developed in the Indian State of Bihar and in adjacent states. The State of Bihar alone accounted for more than half of the world’s total of cases in 1974 up to May 7, and India for more than 80 per cent of all cases. In all four countries where smallpox is still endemic (Bangladesh, Ethiopia, India, and Pakistan), the areas affected have a
World Progress in the Eradication of Smallpox
McAdams, A. J., Jr.: Bronchiolitis obliterans. Am. J. 19: 314, 1955. Med.
_
diminished. More than 90 of all the smallpox cases reported occurred in areas comprising less than 15 per cent of the total land area of the four contries. This decrease in the extent of smallpox endemic areas continues a steady trend that started in 1967 when, at the outset of the program, 30 countries were considered to be endemic. For epidemiologic and operational purposes, these countries were grouped into four regions: South America, Indonesia, mainland Asia, and Africa. Smallpox is deemed to have been eradicated after at least two years have elapsed since the last detected cases, the surveillance measures being considered sufficent to detect any cases during that time. (Continued on page 591)
steadily per
cent
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