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Peri-acinar (paraseptal) emphysema: Its clinical, radiological, and physiological features
Brit.aT. Dis. Chest (,966) 6o, *o.
PERI-ACINAR (PARASEPTAL) EMPHYSEMA: ITS CLINICAL, RADIOLOGICAL, AND PHYSIOLOGICAL FEATURES BY JOHN EDGE High CarleyHospital,Lancashire, GEORGE SIMON AND LYNNE REID Institute of Diseases of the Chest and Brompton Hospital, London
A pathological classification of types of emphysema has little value if it is not correlated with the clinical, functional, and radiological features. Several types of pathological emphysema may be present in the same lung, but the effect of a given type of emphysema on function and on the radiograph can only be established if it occurs alone or is the predominant type. The purpose of this paper is to illustrate the ways in which a particular pathological type of emphysema (periacinar or paraseptal) may present. This type is usually without dyspncea, and may present because of a spontaneous pneumothorax, because of the development of a giant bulla, or because I-2 cm. hair-line ring shadows are found in a routine radiograph. Its name paraseptal is derived from the distribution of abnormally large air-spaces against the pleura, against the fibrous tissue septa penetrating the lung from the pleura, or against the fibrous sheaths encasing bronchi and blood vessels, all these sites being periacinar. The clinical features and radiological appearances are described in two patients. In the first they are related only to certain physiological findings; in the second they are also correlated with the morbid anatomical findings. Case I
Mrs. G. E. G. was aged 33. When aged 9 she had whooping-cough, and since then occasional mild attacks of cough, mucoid sputum and wheeze, which never caused her to miss a day's work. She was otherwise without symptoms until after the birth of her second child in I96I, when she noticed slight breathlessness on effort. Six months later there was a sudden onset of right chest pain and breathlessness, and she was found to have a spontaneous pneumothorax. On examination (I4.9.6I) there was severe orthpncea with some central cyanosis; a generalized high-pitched expiratory rhonchus was heard, and breath sounds were reduced over the left lung and right lower lobe. There was no finger-clubbing, or evidence of heart failure; B.P. I4o/85; liver and spleen were not palpable. She had a little mucoid sputum which contained no pathogens (Receivedfor publication, October 1965)
II
PERI-ACINAR (PARASEPTAL) EMPHYSEMA
or fungi. Hmmoglobin, blood count, E.S.R., blood urea, and serum proteins were all normal. Radiographs showed a right pneumothorax, which was followed a few days later by one on the left. Treatment and Progress. She was treated with aminophylline per rectum and needle aspiration of air from the right hemithorax, but six days after admission developed a left spontaneous pneumothorax also, and her condition deteriorated rapidly. Intercostal catheters were inserted into both pleural spaces with underwater seals, and later suction. An attempt at left pleurodesis with silver nitrate was unsuccessful, and considerable difficulty was experienced in removing enough air to keep the patient alive; one week later (2.1o.61) larger drainage tubes with increased suction were introduced, and this treatment was continued for no less than 63 days before the lungs re-expanded and the tubes could safely be removed. After removal of the tubes her general condition returned to normal, and she declared that she was much less dyspnceic than before admission to hospital. In April 1962 , though free of symptoms, she was readmitted for further investigation because of the unusual radiographic appearances (Fig. I). Lung Function Tests showed remarkably little abnormality. There was a ventilatory defect, with mild airway obstruction improving only slightly after isoprenaline. Surprisingly, her diffusing capacity (steady state CO method) was entirely normal. On exercise, the airway resistance was increased. The lung volumes were virtually the same whether assessed by the body-box or vital capacity, indicating that all parts of the lung were well and directly ventilated.
After Isoprenaline F.V.C. 2,600 ml. 2,7oo ml. F.E.V. 1 1,5oo ml. 1,7oo ml. F.E.V./F.V.C. 58 per cent. 84 l./min. M.V.V. 77 1./min. Peak Flow 30o 1./min. 350 1./min. V.C. 2,50o ml. 2,700 ml. (Min. Vent. I3.8 l./min.) D C O at rest i8. 5 ml./min./mm.Hg O n exercise 26.8 ml./min./mm.Hg (Min. Vent. I7.I l./min.) CO extraction 42 per cent. Airways resistance at 84 breaths/min. : 3" I cm. H20/1./sec. Airways resistance at I68 breaths/min. : 1.5 cm. H~O/1./sec. Lung volume (pneumometric) = 3.o 1.
Radiological Findings. T h e first radiograph of her chest, taken as a routine during her first pregnancy in July I959, was reported as normal, but further scrutiny shows that several hair-line and fine ring shadows are present medially above both hila. A cluster of curvilinear hair-line shadows is also present in the region of the lower right axilla and adjacent to the upper surface of the diaphragm.
I2
EDGE, SIMON AND REID
A second radiograph fourteen months later was taken as a routine during her second pregnancy; this showed an increase in the diameter of some of the hair-line ring shadows above the right hilum, and at the right base, and a less obvious increase in some of those above the left hilum. A third radiograph a year later (before the pneumothorax incident) showed that the hair-line ring shadows in the lower thirds of both lungs were larger, and that m a n y new ones had appeared, giving the lungs a soap-bubble appearance. The diaphragm was lower and flatter, and the heart size had decreased from I i cm. in the initial radiograph to 9"5 cm. A few small nodular shadows were present in the left mid zone. After successful treatment of the bilateral spontaneous pneumothoraces the chest radiograph eventually showed complete re-expansion on both sides, being much the same as that taken just before the incident (Fig. I). The heart was IO cm. wide and the diaphragm flat but not low. Inspiration and expiration films showed that the right diaphragm moved 4 cm. and the left 4"5 cm. There was good deflation of the lower half of the lungs but not of the apices. The main pulmonary artery, and the hilar and mid lung vessels, were not well seen, but appeared normal on tomography. In the lateral view there was no increase in the size of the retrosternal transradiant area. Tomograms show m a n y ring shadows, mostly 2 cm. in diameter, with a wall of hair-line thickness, and all lying in a subpleural position (Fig. 2). There are also m a n y horizontal line shadows extending to the pleura, but the transradiant space they enclose is often poorly demarcated on its deep aspect. Some similar hair-line ring shadows are seen deep in the lung, but adjacent to the interlobar pleura and near the hilum (Fig. 2). When last seen, in August 1962 , she was living a normal life, and denied any dyspncea, whilst a chest radiograph (15.8.62) showed little change in the size and number of the ring and line shadows. Her condition was reported unchanged in March 1965 . Comment. The radiographic appearances are unusual with the numerous 2 cm. ring shadows lying mainly subpleurally; and, although they appear ringshaped in the plain radiograph, the tomograms reveal that the wall is incomplete on the deep or lung side, suggesting that these ring shadows outline emphysematous spaces and are not the complete ring shadows of a cyst. Septa and infolded pleura are probably responsible for the shadows. The respiratory function tests, showing the lung to be completely ventilated, support this interpretation of the radiographic appearances. The apparent paradox of gross emphysema, but without restriction of movement of the diaphragm as seen on postero-anterior-view radiographs, with normal diffusion studies and minimal impairment of ventilation, appears to be resolved by lateral tomography which shows that the emphysema is situated peripherally: as the individual bullm are relatively small, they evidently do not much interfere with bronchial and bronchiolar function. There is probably some relaxation of the relatively normal underlying lung, so that its volume at maximum expansion of the chest is less than it would be in the absence o f the peripheral emphysema, and the airways are therefore partly relaxed. The
PERI-ACINAR (PARASEPTAL) EMPHYSEMA
~3
bronchi and bronchioli may therefore be expected to collapse and " t r a p " air before the transpulmonary pressure at which this normally occurs is attained, accounting for minimal impairment of ventilation. Case 2
Mr. G. P., aged 53, was perfectly well until I957, when he experienced a severe attack of breathlessness at rest, which lasted a couple of hours. In 1958 he first noticed undue dyspnoea on effort, which has gradually progressed since. O n 9.8.6I he experienced a second attack of severe breathlessness, and he was admitted to hospital a few days later. On examination he was found to have heart failure, with signs of mitral incompetence; this was considered to be trivial, and insufficient to account for the heart failure. The breath sounds over the fight lung anteriorly were diminished, there was hyper-resonance at this site, and the trachea was deviated to the left. Blood investigations were normal, except that the blood urea was persistently raised at about 75 mgm. per cent. Lung function tests showed impaired (5 ° per cent.) carbon monoxide transfer even during exercise, together with some airway obstruction, partly reversible after isoprenaline. The abnormality present was, however, considered insufficient to account for the degree of dyspncea present.
After Isoprenaline F.V.C. I sec. F.E.V. 1 F.E.V.1/F.V.C. M.V.V. Peak Flow V.C.
2,000 ml. 1,3oo ml. 65 per cent. 49 1./rain. 26o 1./min. 2,2oo ml.
2,200 ml. 1,4oo ml. 64 per cent. 28o l./min. 2,5oo ml.
Carbon Monoxide Diffusion Capacity at rest I2"5 ml./min.mm.Hg (Min. vent. Io.8 1./min.) on exercise i6-2 ml./min.mm.Hg (Min. vent. I8.o 1./min.)
RadiologicalFindings. On admission (I96i) a radiograph (Fig. 3) showed the diaphragm to be somewhat flat, and lying between the 6th and 7th ribs. The diameter of the heart was 15 cm., the main pulmonary artery was normal, and in some areas the vascular pattern was seen to be normal; these findings precluded the presence of gross widespread emphysema with air trapping. There was a 7 cm. air space in the right mid zone compressing the surrounding lung. O n the left side an avascular area was seen in the upper zone with numerous hair-line shadows lying more or less horizontally, some of which reached the pleura, particularly anteriorly. There was evidence of old tuberculosis in the posterior segment of the right upper lobe. A lateral view confirmed the flat diaphragm, and showed a very large retrosternal translucency, together with a translucency posteriorly demarcated by a vertical hair-line.
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EDGE, SIMON AND REID
Tomograms. Posterior-view tomograms showed that the translucent space in the right axilla extended from back to front. The calcified tuberculous lesions lay mainly posteriorly, and the hair-line shadows anteriorly. An earlier film, taken in 1952 , showed that the heart was the same size, but the diaphragm was then higher--being at the level of the sixth r i b - - a n d not as flat as in the later films. During the nine years the translucent area at the apex grew to extend lower, and the hairlines, particularly the medial ones, became more conspicuous. The right-sided air space had appeared between these films, whilst the avascularity laterally, at the right base, and at the left apex, had increased somewhat. Treatment and Progress. The heart failure was effectively treated with rest, digitalis, and diuretics. It was thought to have been precipitated by the pulmonary disease, either a tension pneumothorax or a large bulla. Particularly in view of the short history, and the sharp attack of dyspncea before admission, a tension pneumothorax was considered more likely, and, in an attempt to obliterate the space, thoracoscopy was carried out on 21.9.61. A large space was found to extend down to the diaphragm anteriorly, and medially to the pericardium; and " n o bull~e were seen". Silver nitrate was introduced in an attempt to secure pleurodesis, but post-operatively, in spite of two intercostal tubes and intensive suction, it was found to be impossible to control the air leak. Right thoracotomy was carried out on 8. lO.61, when the tube was found to lie in a large bulla, which, coming from the anterior segment of the upper lobe, filled the hemi-thorax, stretching forward in front of the heart and mediastinum. The remainder of the right upper lobe was found to be almost completely involved in a system of large thin-walled bull~e, whilst the mid and lower lobes contained numerous small marginal bullm only. The largest bulla was excised, in the hope that this would suffice; but the air leak could not be stopped, and it was necessary to proceed to right upper lobectomy. The extra-pleural strip was accompanied by severe hmmorrhage, and, in spite of most careful h~emostasis, persistent oozing occurred both extrapleurally and into the wound; the patient collapsed with cardiac arrest half an hour after returning to the ward. In spite of blood transfusion and the administration of fibrinogen and hydrocortisone, and an immediate second thoracotomy, the hmmorrhage could not be controlled and the patient died five hours later. Autopsy. At autopsy the corners of the left lung were rounded even before it was inflated. In the left upper lobe there were 18 subpleural bullm, some 2 cm. in diameter. They lay particularly over the mediasfinal aspect of the lobe, where they were subpleural in position, with normal underlying alveoli. In addition there were numerous smaller bullm strung along the sharp margin of the lung (Fig. 4), which are clearly shown in the radiograph of the specimen (Fig. 5) : the microscopic appearance is shown in Fig. 6. The pulmonary artery was injected with barium-gelatine solution. At the rounded edges of the lung it was evident that the distended region represented only the subpleural millimetres--certainly not even the depth of an acinus (Fig. 7). The underlying pattern seemed normal. Some pruning of the intra-
PERI-AGINAN (PARASEPTAL) EMPHYSEMA
I5
acinar pattern was seen in the fork between segmental bronchi. The pruning is only at the periphery of the filled pathway. The lung was cut parallel to the mediastinal surface into slices roughly one and a half centimetres thick. In these the lung appeared essentially normal, save for the emphysematous spaces seen under the pleura and against the connective tissue septa and the connective tissue sheaths of veins or bronchoarterial bundles (Fig. 8). Individual air spaces varied from a few millimetres in diameter up to a centimetre. In this lung there was no evidence o f tuberculosis, and the only type of emphysema present was peri-acinar. Right Upper Lobe-resection. From the right upper lobe two large bulI~e arose from the antero-lateral aspect of the anterior segment. At operation the base of these bull~e had been oversewn before resection was decided on. In the posterior part of the lobe were half a dozen collections of caseous material, all less than a centimetre in diameter and well encapsulated by dense fibrous tissue. The lung between these was emphysematous, but no subpleural bulke were seen. In contrast, over the medial aspect of the anterior segment were pouting regions two centimetres in diameter resembling the bullm described in the left lung. The distribution was the same as that of the line shadows detected in the radiograph. The cut surface showed emphysema against the septa deep in the lung. The tuberculous scars were confined to the posterior segment, and the type of emphysema associated with them was different from that found in the anterior part of the lobe, and in the left lung, suggesting that the paraseptal emphysema is not caused by tuberculosis. It would seem that the very large bulla had started as one of the small subpleural ones, illustrating another of the complications of this type of emphysema. The interest of this case is that it was possible to correlate the radiologieal ring shadows at the left apex with the presence of the small bull~e in the specimen. In this case there is no doubt that the rapid ballooning of a peripheral bulla to an enormous size precipitated heart failure, there being only a minor degree of mitral incompetence present at autopsy. The heart failure responded to orthodox treatment; but subsequently surgical removal of the right upper lobe was followed by death from uncontrollable hmmorrhage, evidently due to hypoprothrombimemia.
Discussion
The term " e m p h y s e m a " is now widely accepted to mean abnormally large air spaces within the acinus. Since in the condition under discussion the air spaces of the lung are enlarged, it is by definition emphysema. O n the other hand, the radiographic appearances are not those o f " widespread emphysema" with airway obstruction (Simon, i964) , nor do the respiratory function tests suggest that this type of emphysema gives rise to generalized airway obstruction. It is therefore an example of emphysema which does not cause airway obstruction (Reid, I964).
16,
EDGE, SIMON AND REID
Even in Case I, where the changes were widespread, the diffusion studies pointed to normal alveolar walls, and the body-box studies indicated that all parts of the lung were well and directly ventilated. The slight impairment of the tests for ventilation may have arisen from the space-occupying bull~e producing relaxation of the bronchial tree. T h e volume occupied by the numerous, though relatively small, bull~e would seem considerable; and as the diaphragm was not depressed the volume remaining to the normal alveoli would be reduced. As, even in the normal lung, the end of expiration is marked by airways collapse, the relaxation of the normal lung between the paraseptal lesions probably allowed the airways to reach the end of expiration after a smaller volume of air had been expired.
Pathogenesis The cause of peri-acinar emphysema is not certain. Although it is the subpleural site which favours the development of bull~e, the milder changes of peri-acinar emphysema are seen even deep within the lung, adjacent to fibrous tissue within connective tissue septa, or ensheathing large broncharterial bundles or veins. Although "peri-acinar" describes the situation in relation to the acinus, "paraseptal" is a better description of this type, as it would seem to be only those peri-acinar regions which are also paraseptal that are susceptible: each term has its value in a given context. Several features peculiar to this region--concerning the capillary and elastic-fibre arrangement--may throw light on the development of emphysema at this site. It would seem that capillaries in these alveolar walls against connective tissue are less numerous t h a n in those alveolar walls with air spaces on either side (Miller, 1950). In recent studies Elliott (1964) and Elliott and Reid (x 965) have shown that the presence of numerous accessory arteries provides a rich arterial and arteriolar supply to the alveoli adjacent to the smaller pulmonary artery branches--a supply not enjoyed by those peripheral alveoli lying against fibrous septa or pleura. This would produce a region of the acinus which by virtue of its reduced vascularity might have a higher compliance. Furthermore, Boyden (I965) has recently shown that arteries pass from one acinus to the next where alveolar tissue is continuous. This has not been seen to occur across a fibrous tissue septum. During lung development the elastic fibres appear first round bronchioli in the centre of the acinus, and even at birth none are present against the pleura (Loosli, i963). Although lung "elasticity" cannot be related only to the behaviour of elastic fibres, the local reduction in their number may point to an additional factor allowing the lung in the peripheral region to be more easily stretched.
Differential Diagnosis The radiographic appearances of hair-line ring and polygonal shadows are unusual in a chest radiograph and may be characteristic of this condition. The radiograph in peri-acinar emphysema is reminiscent of cystic bronchiectasis, but the ring shadows in the former are more numerous and thinner-walled and
PLATE I
Fic. i.--Paraseptal (periacinar) emphysema. Intersecting hair-line and ring shadows throughout the lungs, most marked in basal regions. Case I, woman aged 33.
FIG. m--Paraseptal (periacinar) emphysema. Same case as Fig. i (lateral view tomogram). Subpleural position of linear shadows anteriorly and posteriorly.
Fro. 4.--~vfarginal bulla~ along sharp edge. FIG. 3.--Paraseptal (periacinar) emphysema. Intersecting line shadows left upper lobe. Bulla right mid zone, found at thoracotomy to extend to pericardium anteriorly. Case 2. Paraseptal emphysema confirmed at autopsy.
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PLATE
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PERI-ACiNAR (PARASEPTAL) EMPHYSEMA
i7
tend to be polygonal. In bronchiectasis the ring shadows can be filled with radio-opaque oil. In the honeycomb lung of histiocytosis X or interstitial fibrosis the shadows are usually smaller and thicker-walled; if larger they may represent bull~e in any case. In neither of these is the subpleural distribution seen. At first sight the subpleural paraseptal lesions, particularly the marginal variety, resemble the blebs commonly associated with spontaneous pneumothorax as described by Miller (z 95 o) : but both those over the flat surfaces and the marginal ones are bull~e. The pleura has two layers of elastic fibres, the external following the contour of the lung, the internal lying in the walls of the outer layer of alveoli and dipping into the lung along the connective tissue septa. Miller used the term " b l e b " to describe a collection of air within the pleura external to the alveolar or internal elastic layer. This means that in a bleb the collection of air lifts the pleura over the lung and is not confined by septa: it is an example of interstitial emphysema. A bulla on the other hand represents alveoli, and thus lies internal to both elastic layers, although these may not be separately distinguishable in a large bulla (Fig. 9). The relative frequency of blebs and bull~e in the production of spontaneous pneumothorax is unknown.
BLEB
BULLA Pleira
Elastic fibres
Connective tissue septum
Fro. 9.--Diagram illustrating difference between bulla and bleb. These paraseptal and subpleural lesions represent alveoli. Over the flat surface it is easier to see that alveoli are continuous with underlying lung: this also applies to the marginal variety, and the fact that the string of pleural elevations consists of numerous small dilatations held down by lung distinguishes it from the form of the bleb, in which the pleura would be evenly and smoothly elevated. The " b l e b " Miller illustrated by photomicrography is in fact probably a bulla, as its edges are confined by connective tissue septa. While the marginal bulla~ are not an uncommon finding at autopsy, it is rare for the bulhe to be sufficiently large or numerous to give rise to the radiographic appearance and clinical symptoms described here. Blebs are rare in VOL.LXZ 2* +
18
EDGE, SIMON A N D REID
the human lung, possibly because the free operation of collateral ventilation prevents the building up of enough pressure to rupture alveoli. By contrast the cow's lung is subdivided into isolated units by connective tissue across which collateral ventilation does not occur. Interstitial emphysema seems relatively more common in cattle and, with it, the formation of blebs.
Summary Two patients with paraseptal (peri-acinar) emphysema are described. Bilateral spontaneous pneumothorax occurred in one patient and rapid enlargement of a bulla in the other, in each case causing severe acute dyspnoea: neither had complained of dyspncea before. The radiographic features were the combination of hair-line ring and polygonal shadOws with avascular areas distributed under the pleura, characteristic of the condition. Pulmonary function studies showed remarkably little airway obstruction and the lungs were evenly ventilated: the minor degree of impairment was consistent with a cushioning effect of the peripheral bull~e. One of the patients died after operation, enabling detailed pathological studies of this unusual condition to be made. REFERENCES BOYD~N, E. A. (1965). Personal communication. ELuoa~r, F. M. (1964). "The Pulmonary Artery System in Normal and Diseased Lungs-Structure in Relation to Pattern of Branching." Ph.D. Thesis, London. ELLIOTT, F. M., & RZXD,L. (I965). Clin. Radiol., x6, i93. LoosLi, C. G., & POTTER, E. L. (I959). Arner. Rev. resp. Dis., 8o, 5. MILLER, W. S. (x95o). The Lung, 2nd ed. Springfield, Illinois: Charles C. Thomas. REID, L. The Pathology of Emphysema. London: Lloyd Luke Medieal Books Ltd. (In press.) SIMON, G. (x964). Clin. Radiol., x5, 293.
PERI-ACINAR (PARASEPTAL) EMPHYSEMA: ITS CLINICAL, RADIOLOGICAL, AND PHYSIOLOGICAL FEATURES BY JOHN EDGE High CarleyHospital,Lancashire, GEORGE SIMON AND LYNNE REID Institute of Diseases of the Chest and Brompton Hospital, London
A pathological classification of types of emphysema has little value if it is not correlated with the clinical, functional, and radiological features. Several types of pathological emphysema may be present in the same lung, but the effect of a given type of emphysema on function and on the radiograph can only be established if it occurs alone or is the predominant type. The purpose of this paper is to illustrate the ways in which a particular pathological type of emphysema (periacinar or paraseptal) may present. This type is usually without dyspncea, and may present because of a spontaneous pneumothorax, because of the development of a giant bulla, or because I-2 cm. hair-line ring shadows are found in a routine radiograph. Its name paraseptal is derived from the distribution of abnormally large air-spaces against the pleura, against the fibrous tissue septa penetrating the lung from the pleura, or against the fibrous sheaths encasing bronchi and blood vessels, all these sites being periacinar. The clinical features and radiological appearances are described in two patients. In the first they are related only to certain physiological findings; in the second they are also correlated with the morbid anatomical findings. Case I
Mrs. G. E. G. was aged 33. When aged 9 she had whooping-cough, and since then occasional mild attacks of cough, mucoid sputum and wheeze, which never caused her to miss a day's work. She was otherwise without symptoms until after the birth of her second child in I96I, when she noticed slight breathlessness on effort. Six months later there was a sudden onset of right chest pain and breathlessness, and she was found to have a spontaneous pneumothorax. On examination (I4.9.6I) there was severe orthpncea with some central cyanosis; a generalized high-pitched expiratory rhonchus was heard, and breath sounds were reduced over the left lung and right lower lobe. There was no finger-clubbing, or evidence of heart failure; B.P. I4o/85; liver and spleen were not palpable. She had a little mucoid sputum which contained no pathogens (Receivedfor publication, October 1965)
II
PERI-ACINAR (PARASEPTAL) EMPHYSEMA
or fungi. Hmmoglobin, blood count, E.S.R., blood urea, and serum proteins were all normal. Radiographs showed a right pneumothorax, which was followed a few days later by one on the left. Treatment and Progress. She was treated with aminophylline per rectum and needle aspiration of air from the right hemithorax, but six days after admission developed a left spontaneous pneumothorax also, and her condition deteriorated rapidly. Intercostal catheters were inserted into both pleural spaces with underwater seals, and later suction. An attempt at left pleurodesis with silver nitrate was unsuccessful, and considerable difficulty was experienced in removing enough air to keep the patient alive; one week later (2.1o.61) larger drainage tubes with increased suction were introduced, and this treatment was continued for no less than 63 days before the lungs re-expanded and the tubes could safely be removed. After removal of the tubes her general condition returned to normal, and she declared that she was much less dyspnceic than before admission to hospital. In April 1962 , though free of symptoms, she was readmitted for further investigation because of the unusual radiographic appearances (Fig. I). Lung Function Tests showed remarkably little abnormality. There was a ventilatory defect, with mild airway obstruction improving only slightly after isoprenaline. Surprisingly, her diffusing capacity (steady state CO method) was entirely normal. On exercise, the airway resistance was increased. The lung volumes were virtually the same whether assessed by the body-box or vital capacity, indicating that all parts of the lung were well and directly ventilated.
After Isoprenaline F.V.C. 2,600 ml. 2,7oo ml. F.E.V. 1 1,5oo ml. 1,7oo ml. F.E.V./F.V.C. 58 per cent. 84 l./min. M.V.V. 77 1./min. Peak Flow 30o 1./min. 350 1./min. V.C. 2,50o ml. 2,700 ml. (Min. Vent. I3.8 l./min.) D C O at rest i8. 5 ml./min./mm.Hg O n exercise 26.8 ml./min./mm.Hg (Min. Vent. I7.I l./min.) CO extraction 42 per cent. Airways resistance at 84 breaths/min. : 3" I cm. H20/1./sec. Airways resistance at I68 breaths/min. : 1.5 cm. H~O/1./sec. Lung volume (pneumometric) = 3.o 1.
Radiological Findings. T h e first radiograph of her chest, taken as a routine during her first pregnancy in July I959, was reported as normal, but further scrutiny shows that several hair-line and fine ring shadows are present medially above both hila. A cluster of curvilinear hair-line shadows is also present in the region of the lower right axilla and adjacent to the upper surface of the diaphragm.
I2
EDGE, SIMON AND REID
A second radiograph fourteen months later was taken as a routine during her second pregnancy; this showed an increase in the diameter of some of the hair-line ring shadows above the right hilum, and at the right base, and a less obvious increase in some of those above the left hilum. A third radiograph a year later (before the pneumothorax incident) showed that the hair-line ring shadows in the lower thirds of both lungs were larger, and that m a n y new ones had appeared, giving the lungs a soap-bubble appearance. The diaphragm was lower and flatter, and the heart size had decreased from I i cm. in the initial radiograph to 9"5 cm. A few small nodular shadows were present in the left mid zone. After successful treatment of the bilateral spontaneous pneumothoraces the chest radiograph eventually showed complete re-expansion on both sides, being much the same as that taken just before the incident (Fig. I). The heart was IO cm. wide and the diaphragm flat but not low. Inspiration and expiration films showed that the right diaphragm moved 4 cm. and the left 4"5 cm. There was good deflation of the lower half of the lungs but not of the apices. The main pulmonary artery, and the hilar and mid lung vessels, were not well seen, but appeared normal on tomography. In the lateral view there was no increase in the size of the retrosternal transradiant area. Tomograms show m a n y ring shadows, mostly 2 cm. in diameter, with a wall of hair-line thickness, and all lying in a subpleural position (Fig. 2). There are also m a n y horizontal line shadows extending to the pleura, but the transradiant space they enclose is often poorly demarcated on its deep aspect. Some similar hair-line ring shadows are seen deep in the lung, but adjacent to the interlobar pleura and near the hilum (Fig. 2). When last seen, in August 1962 , she was living a normal life, and denied any dyspncea, whilst a chest radiograph (15.8.62) showed little change in the size and number of the ring and line shadows. Her condition was reported unchanged in March 1965 . Comment. The radiographic appearances are unusual with the numerous 2 cm. ring shadows lying mainly subpleurally; and, although they appear ringshaped in the plain radiograph, the tomograms reveal that the wall is incomplete on the deep or lung side, suggesting that these ring shadows outline emphysematous spaces and are not the complete ring shadows of a cyst. Septa and infolded pleura are probably responsible for the shadows. The respiratory function tests, showing the lung to be completely ventilated, support this interpretation of the radiographic appearances. The apparent paradox of gross emphysema, but without restriction of movement of the diaphragm as seen on postero-anterior-view radiographs, with normal diffusion studies and minimal impairment of ventilation, appears to be resolved by lateral tomography which shows that the emphysema is situated peripherally: as the individual bullm are relatively small, they evidently do not much interfere with bronchial and bronchiolar function. There is probably some relaxation of the relatively normal underlying lung, so that its volume at maximum expansion of the chest is less than it would be in the absence o f the peripheral emphysema, and the airways are therefore partly relaxed. The
PERI-ACINAR (PARASEPTAL) EMPHYSEMA
~3
bronchi and bronchioli may therefore be expected to collapse and " t r a p " air before the transpulmonary pressure at which this normally occurs is attained, accounting for minimal impairment of ventilation. Case 2
Mr. G. P., aged 53, was perfectly well until I957, when he experienced a severe attack of breathlessness at rest, which lasted a couple of hours. In 1958 he first noticed undue dyspnoea on effort, which has gradually progressed since. O n 9.8.6I he experienced a second attack of severe breathlessness, and he was admitted to hospital a few days later. On examination he was found to have heart failure, with signs of mitral incompetence; this was considered to be trivial, and insufficient to account for the heart failure. The breath sounds over the fight lung anteriorly were diminished, there was hyper-resonance at this site, and the trachea was deviated to the left. Blood investigations were normal, except that the blood urea was persistently raised at about 75 mgm. per cent. Lung function tests showed impaired (5 ° per cent.) carbon monoxide transfer even during exercise, together with some airway obstruction, partly reversible after isoprenaline. The abnormality present was, however, considered insufficient to account for the degree of dyspncea present.
After Isoprenaline F.V.C. I sec. F.E.V. 1 F.E.V.1/F.V.C. M.V.V. Peak Flow V.C.
2,000 ml. 1,3oo ml. 65 per cent. 49 1./rain. 26o 1./min. 2,2oo ml.
2,200 ml. 1,4oo ml. 64 per cent. 28o l./min. 2,5oo ml.
Carbon Monoxide Diffusion Capacity at rest I2"5 ml./min.mm.Hg (Min. vent. Io.8 1./min.) on exercise i6-2 ml./min.mm.Hg (Min. vent. I8.o 1./min.)
RadiologicalFindings. On admission (I96i) a radiograph (Fig. 3) showed the diaphragm to be somewhat flat, and lying between the 6th and 7th ribs. The diameter of the heart was 15 cm., the main pulmonary artery was normal, and in some areas the vascular pattern was seen to be normal; these findings precluded the presence of gross widespread emphysema with air trapping. There was a 7 cm. air space in the right mid zone compressing the surrounding lung. O n the left side an avascular area was seen in the upper zone with numerous hair-line shadows lying more or less horizontally, some of which reached the pleura, particularly anteriorly. There was evidence of old tuberculosis in the posterior segment of the right upper lobe. A lateral view confirmed the flat diaphragm, and showed a very large retrosternal translucency, together with a translucency posteriorly demarcated by a vertical hair-line.
I4
EDGE, SIMON AND REID
Tomograms. Posterior-view tomograms showed that the translucent space in the right axilla extended from back to front. The calcified tuberculous lesions lay mainly posteriorly, and the hair-line shadows anteriorly. An earlier film, taken in 1952 , showed that the heart was the same size, but the diaphragm was then higher--being at the level of the sixth r i b - - a n d not as flat as in the later films. During the nine years the translucent area at the apex grew to extend lower, and the hairlines, particularly the medial ones, became more conspicuous. The right-sided air space had appeared between these films, whilst the avascularity laterally, at the right base, and at the left apex, had increased somewhat. Treatment and Progress. The heart failure was effectively treated with rest, digitalis, and diuretics. It was thought to have been precipitated by the pulmonary disease, either a tension pneumothorax or a large bulla. Particularly in view of the short history, and the sharp attack of dyspncea before admission, a tension pneumothorax was considered more likely, and, in an attempt to obliterate the space, thoracoscopy was carried out on 21.9.61. A large space was found to extend down to the diaphragm anteriorly, and medially to the pericardium; and " n o bull~e were seen". Silver nitrate was introduced in an attempt to secure pleurodesis, but post-operatively, in spite of two intercostal tubes and intensive suction, it was found to be impossible to control the air leak. Right thoracotomy was carried out on 8. lO.61, when the tube was found to lie in a large bulla, which, coming from the anterior segment of the upper lobe, filled the hemi-thorax, stretching forward in front of the heart and mediastinum. The remainder of the right upper lobe was found to be almost completely involved in a system of large thin-walled bull~e, whilst the mid and lower lobes contained numerous small marginal bullm only. The largest bulla was excised, in the hope that this would suffice; but the air leak could not be stopped, and it was necessary to proceed to right upper lobectomy. The extra-pleural strip was accompanied by severe hmmorrhage, and, in spite of most careful h~emostasis, persistent oozing occurred both extrapleurally and into the wound; the patient collapsed with cardiac arrest half an hour after returning to the ward. In spite of blood transfusion and the administration of fibrinogen and hydrocortisone, and an immediate second thoracotomy, the hmmorrhage could not be controlled and the patient died five hours later. Autopsy. At autopsy the corners of the left lung were rounded even before it was inflated. In the left upper lobe there were 18 subpleural bullm, some 2 cm. in diameter. They lay particularly over the mediasfinal aspect of the lobe, where they were subpleural in position, with normal underlying alveoli. In addition there were numerous smaller bullm strung along the sharp margin of the lung (Fig. 4), which are clearly shown in the radiograph of the specimen (Fig. 5) : the microscopic appearance is shown in Fig. 6. The pulmonary artery was injected with barium-gelatine solution. At the rounded edges of the lung it was evident that the distended region represented only the subpleural millimetres--certainly not even the depth of an acinus (Fig. 7). The underlying pattern seemed normal. Some pruning of the intra-
PERI-AGINAN (PARASEPTAL) EMPHYSEMA
I5
acinar pattern was seen in the fork between segmental bronchi. The pruning is only at the periphery of the filled pathway. The lung was cut parallel to the mediastinal surface into slices roughly one and a half centimetres thick. In these the lung appeared essentially normal, save for the emphysematous spaces seen under the pleura and against the connective tissue septa and the connective tissue sheaths of veins or bronchoarterial bundles (Fig. 8). Individual air spaces varied from a few millimetres in diameter up to a centimetre. In this lung there was no evidence o f tuberculosis, and the only type of emphysema present was peri-acinar. Right Upper Lobe-resection. From the right upper lobe two large bulI~e arose from the antero-lateral aspect of the anterior segment. At operation the base of these bull~e had been oversewn before resection was decided on. In the posterior part of the lobe were half a dozen collections of caseous material, all less than a centimetre in diameter and well encapsulated by dense fibrous tissue. The lung between these was emphysematous, but no subpleural bulke were seen. In contrast, over the medial aspect of the anterior segment were pouting regions two centimetres in diameter resembling the bullm described in the left lung. The distribution was the same as that of the line shadows detected in the radiograph. The cut surface showed emphysema against the septa deep in the lung. The tuberculous scars were confined to the posterior segment, and the type of emphysema associated with them was different from that found in the anterior part of the lobe, and in the left lung, suggesting that the paraseptal emphysema is not caused by tuberculosis. It would seem that the very large bulla had started as one of the small subpleural ones, illustrating another of the complications of this type of emphysema. The interest of this case is that it was possible to correlate the radiologieal ring shadows at the left apex with the presence of the small bull~e in the specimen. In this case there is no doubt that the rapid ballooning of a peripheral bulla to an enormous size precipitated heart failure, there being only a minor degree of mitral incompetence present at autopsy. The heart failure responded to orthodox treatment; but subsequently surgical removal of the right upper lobe was followed by death from uncontrollable hmmorrhage, evidently due to hypoprothrombimemia.
Discussion
The term " e m p h y s e m a " is now widely accepted to mean abnormally large air spaces within the acinus. Since in the condition under discussion the air spaces of the lung are enlarged, it is by definition emphysema. O n the other hand, the radiographic appearances are not those o f " widespread emphysema" with airway obstruction (Simon, i964) , nor do the respiratory function tests suggest that this type of emphysema gives rise to generalized airway obstruction. It is therefore an example of emphysema which does not cause airway obstruction (Reid, I964).
16,
EDGE, SIMON AND REID
Even in Case I, where the changes were widespread, the diffusion studies pointed to normal alveolar walls, and the body-box studies indicated that all parts of the lung were well and directly ventilated. The slight impairment of the tests for ventilation may have arisen from the space-occupying bull~e producing relaxation of the bronchial tree. T h e volume occupied by the numerous, though relatively small, bull~e would seem considerable; and as the diaphragm was not depressed the volume remaining to the normal alveoli would be reduced. As, even in the normal lung, the end of expiration is marked by airways collapse, the relaxation of the normal lung between the paraseptal lesions probably allowed the airways to reach the end of expiration after a smaller volume of air had been expired.
Pathogenesis The cause of peri-acinar emphysema is not certain. Although it is the subpleural site which favours the development of bull~e, the milder changes of peri-acinar emphysema are seen even deep within the lung, adjacent to fibrous tissue within connective tissue septa, or ensheathing large broncharterial bundles or veins. Although "peri-acinar" describes the situation in relation to the acinus, "paraseptal" is a better description of this type, as it would seem to be only those peri-acinar regions which are also paraseptal that are susceptible: each term has its value in a given context. Several features peculiar to this region--concerning the capillary and elastic-fibre arrangement--may throw light on the development of emphysema at this site. It would seem that capillaries in these alveolar walls against connective tissue are less numerous t h a n in those alveolar walls with air spaces on either side (Miller, 1950). In recent studies Elliott (1964) and Elliott and Reid (x 965) have shown that the presence of numerous accessory arteries provides a rich arterial and arteriolar supply to the alveoli adjacent to the smaller pulmonary artery branches--a supply not enjoyed by those peripheral alveoli lying against fibrous septa or pleura. This would produce a region of the acinus which by virtue of its reduced vascularity might have a higher compliance. Furthermore, Boyden (I965) has recently shown that arteries pass from one acinus to the next where alveolar tissue is continuous. This has not been seen to occur across a fibrous tissue septum. During lung development the elastic fibres appear first round bronchioli in the centre of the acinus, and even at birth none are present against the pleura (Loosli, i963). Although lung "elasticity" cannot be related only to the behaviour of elastic fibres, the local reduction in their number may point to an additional factor allowing the lung in the peripheral region to be more easily stretched.
Differential Diagnosis The radiographic appearances of hair-line ring and polygonal shadows are unusual in a chest radiograph and may be characteristic of this condition. The radiograph in peri-acinar emphysema is reminiscent of cystic bronchiectasis, but the ring shadows in the former are more numerous and thinner-walled and
PLATE I
Fic. i.--Paraseptal (periacinar) emphysema. Intersecting hair-line and ring shadows throughout the lungs, most marked in basal regions. Case I, woman aged 33.
FIG. m--Paraseptal (periacinar) emphysema. Same case as Fig. i (lateral view tomogram). Subpleural position of linear shadows anteriorly and posteriorly.
Fro. 4.--~vfarginal bulla~ along sharp edge. FIG. 3.--Paraseptal (periacinar) emphysema. Intersecting line shadows left upper lobe. Bulla right mid zone, found at thoracotomy to extend to pericardium anteriorly. Case 2. Paraseptal emphysema confirmed at autopsy.
2+
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PLATE
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PERI-ACiNAR (PARASEPTAL) EMPHYSEMA
i7
tend to be polygonal. In bronchiectasis the ring shadows can be filled with radio-opaque oil. In the honeycomb lung of histiocytosis X or interstitial fibrosis the shadows are usually smaller and thicker-walled; if larger they may represent bull~e in any case. In neither of these is the subpleural distribution seen. At first sight the subpleural paraseptal lesions, particularly the marginal variety, resemble the blebs commonly associated with spontaneous pneumothorax as described by Miller (z 95 o) : but both those over the flat surfaces and the marginal ones are bull~e. The pleura has two layers of elastic fibres, the external following the contour of the lung, the internal lying in the walls of the outer layer of alveoli and dipping into the lung along the connective tissue septa. Miller used the term " b l e b " to describe a collection of air within the pleura external to the alveolar or internal elastic layer. This means that in a bleb the collection of air lifts the pleura over the lung and is not confined by septa: it is an example of interstitial emphysema. A bulla on the other hand represents alveoli, and thus lies internal to both elastic layers, although these may not be separately distinguishable in a large bulla (Fig. 9). The relative frequency of blebs and bull~e in the production of spontaneous pneumothorax is unknown.
BLEB
BULLA Pleira
Elastic fibres
Connective tissue septum
Fro. 9.--Diagram illustrating difference between bulla and bleb. These paraseptal and subpleural lesions represent alveoli. Over the flat surface it is easier to see that alveoli are continuous with underlying lung: this also applies to the marginal variety, and the fact that the string of pleural elevations consists of numerous small dilatations held down by lung distinguishes it from the form of the bleb, in which the pleura would be evenly and smoothly elevated. The " b l e b " Miller illustrated by photomicrography is in fact probably a bulla, as its edges are confined by connective tissue septa. While the marginal bulla~ are not an uncommon finding at autopsy, it is rare for the bulhe to be sufficiently large or numerous to give rise to the radiographic appearance and clinical symptoms described here. Blebs are rare in VOL.LXZ 2* +
18
EDGE, SIMON A N D REID
the human lung, possibly because the free operation of collateral ventilation prevents the building up of enough pressure to rupture alveoli. By contrast the cow's lung is subdivided into isolated units by connective tissue across which collateral ventilation does not occur. Interstitial emphysema seems relatively more common in cattle and, with it, the formation of blebs.
Summary Two patients with paraseptal (peri-acinar) emphysema are described. Bilateral spontaneous pneumothorax occurred in one patient and rapid enlargement of a bulla in the other, in each case causing severe acute dyspnoea: neither had complained of dyspncea before. The radiographic features were the combination of hair-line ring and polygonal shadOws with avascular areas distributed under the pleura, characteristic of the condition. Pulmonary function studies showed remarkably little airway obstruction and the lungs were evenly ventilated: the minor degree of impairment was consistent with a cushioning effect of the peripheral bull~e. One of the patients died after operation, enabling detailed pathological studies of this unusual condition to be made. REFERENCES BOYD~N, E. A. (1965). Personal communication. ELuoa~r, F. M. (1964). "The Pulmonary Artery System in Normal and Diseased Lungs-Structure in Relation to Pattern of Branching." Ph.D. Thesis, London. ELLIOTT, F. M., & RZXD,L. (I965). Clin. Radiol., x6, i93. LoosLi, C. G., & POTTER, E. L. (I959). Arner. Rev. resp. Dis., 8o, 5. MILLER, W. S. (x95o). The Lung, 2nd ed. Springfield, Illinois: Charles C. Thomas. REID, L. The Pathology of Emphysema. London: Lloyd Luke Medieal Books Ltd. (In press.) SIMON, G. (x964). Clin. Radiol., x5, 293.