Pulmonary Agenesis

Pulmonary Agenesis DENNIS

I

M. L. ROSENBERG, M.D., F.C.C.P* New Orleans, Louisiana

been evidence of observation and the recording of a medical curiosity. Presumably no clinical information could reasonably be expected from the early reports. Late in the 19th century, case reports began to appear, although isolated remarks on the condition had been included in earlier texts. In this century, pulmonary agenesis is, each year, reported with increasing frequency, probably because of improved diagnostic methods and more widespread awareness of the possibility of such an anomaly. The literature on the subject is far too voluminous for survey in a presentation of case reports.

N REFERENCE TO THE DEVELOPMENT OF

the lungs, indiscriminate usage of the terms agenesis, aplasia, and hypoplasia has created a certain amount of confusion in the literature. Agenesis has been used to denote complete absence of lungs as well as to describe conditions in which a variable amount of pulmonary tissue exists with a rudimentary bronchus. To clarify communication, a universal classification should be adopted and the terms used only to connote their precise meanings. Actually, agenesis should be the designation for failure of development of lung tissue and aplasia for incomplete development. Potter' classified all the malformations of the lung, but earlier Schneider" had suggested a classification according to the degree of defect: Group 1: True absence of lung or bronchus and no vascular supply to the affected side. Group 2: A primordial bud (a tiny outpocketing of the trachea as bronchus) but no lung tissue. Group 3: Extreme hypoplasia with no true lung tissue in which a bronchus of small caliber ends in a fleshy structure without lobes and lies within the mediastinum. Three case histories within our personal experience may contribute to the existing knowledge of such conditions.

EMBRYOLOGIC ORIGIN

The etiology of pulmonary agenesis is unknown; however, the lesion is commonly thought to occur because of inherently faulty germ plasm.t" with the result that development of the pulmonary, vascular, and respiratory systems is defective. A developmental error of genetic origin is presumed, since the pulmonary vessels to the missing lobes or lung are usually absent, and other abnormalities frequently coexist. Arey" has described the respiratory system as beginning with an evagination that starts on the ventral side of the esophagus and resembles a groove. The lung buds then grow out from the posterior end of this laryngotracheal groove, and, later, the anlage of the trachea and esophagus is separated by a constriction. From the lung buds, the bronchi arise. In subsequent stages of development" these epithelial evaginations push out into the connective tissue of the developing lungs and give rise to lobar bronchi. Each of the latter give rise, in tum, to segmental bronchi. This description suggests that pulmonary OT lobar agenesis must occur, respectively, about the same time that the lung buds

HISTORIC BACKGROUND

Although agenesis of the lung is an infrequent anomaly, it is by no means a newly discovered one. The first description of the condition has been attributed to various authors, but the earliest of the reputed observers was De Pozzi in 1673.3 That instance, however, can only have

* Assistant

Professor of Surgery, Tulane Univer-

sity School of Medicine.

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PULMONARY AGENESIS

first appear (Horizon XIII, 28± one day after ovulation) 48 or the time that the lobar bronchi first arise (Horizon XV, 31-32 days after ovulation). 49 Ellis7 considered that the malformation of the pulmonary circulation was the primary malformation, with subsequent failure of development of the pulmonary tree, although not all investigators agree. Wilson and Warkany8 have demonstrated agenesis of the left lungs in rat fetuses subjected to maternal vitamin A deficiency. In the fetuses, the pulmonary arteries were also absent, and there were additional defects also. Warkany' has shown experimentally that maternal environmental changes may affect the embryo and can result in congenital anomalies which are known to be hereditary in human subjects. It has been postulated that a defect similar to those from nutritional deficiency may be produced by diseases of the placenta, or by infectious agents that affect normal development by modification of the vascular supply. AGE AND SEX DISTRIBUTION

agenesis is definitely not incompatible with survival.13 In Valle's series, agenesis occurred in 49 males (25 on the left side, and 22 on the right). In one patient, the involved side was not reported, and in one there was bilateral agenesis. The condition was described by Valle in 67 females (32 on the left side, and 24 on the right, and one bilateral). In 14 cases, the sex was not mentioned. Of the cases in which the involved side was stated, the left lung was absent in 62 and the right in 54. Apparently, in this group no significant difference in incidence existed between the sexes, and both sides were equally affected. Other physicians have also considered the sex dis.. tribution to be about equal.":":" This finding is, however, by no means invariable. Katz, II Stowens," and Lukas" and associates believe absence of the lung or parts of it to be more commonly diagnosed in males. Indeed, Stowens suggested that occurrence in males was approximately twice as frequent. Many investigators have also found the left side to be more often affected. 4 ,6. 1o, lS , 1'1, t l . I J

In a survey of 57 cases taken from the literature, Brescia" and associates found this distribution according to age: stillborn or fetus ._. . .._ 6 newborn . . - -_16 0-1 year . .. 6 2-10 years . ... . . 8 11-20 years _. . .__ . 3 over 20 years 18

While agenesis of one lung is rather a rare condition, lobar agenesis is even more uncommon.f'" Berliner" in 1909 reported an instance of agenesis of the right upper and middle lobes. From that time until 1954, according to Valle," only 14 cases were reported, and in nine of them the right upper and middle lobes were the absent ones.

In the larger group collected by Valle," 53 patients were less than one year of age; 44 were between one and 30 years; 15 were between 31 and 72 years; and in eight, the age was not given. Among the cases he recorded, the youngest was a premature baby (seven months) who lived for only two hours, and the oldest was a 72-yearold woman who died of cerebral hemorrhage." Actually, the condition often goes unrecognized. As many cases are found at postmortem examination as are diagnosed during life. Obviously, unilateral or lobar

DIAGNOSIS

Although the date of the first case described is a matter for disagreement, it is, at least, clear that diagnosis of unilateral pulmonary agenesis made by physical examination of a living patient was not feasible for more than 100 years. Subsequent investigators might have suspected the state in a live patient and later verified it at necropsy, but this sequence was unusual. Actually, before 1942,14 antemortem diagnosis was accomplished in less than ten (probably less than five) cases. Since that

7°

DENNIS M. L. ROSENBERG

date, however, many more cases have been reported during the life of the patient, presumably because of the wider use of bronchoscopy, bronchography, and angiography in the study of obscure pulmonary conditions. Clinically, the chest may be found to be asymmetrical; there may be flattening of the affected side ;30-33 and an inspiratory lag may also be noted. Usually, though, the shape and the movements of the chest are normal. The trachea is often found to be deviated towards the side of the missing pulmonary tissue, and the heart and mediastinum comparably displaced.31J134J1u If the right lung is absent, the cardiac apex will be noted on the right side, so that the impression is that of dextrocardia." On the posterior chest wall, heart sounds are audible, and the heart rotates also. There may be no breath sounds over the affected side, with obvious dullness to percussion." The remaining lung is likely to seem normal and the physical findings on that side will be the expected ones. Physical findings can be normal, particularly in the upper portion of the side affected, if there is herniation of the existing lung. If the remaining lung is emphysematous, hyperresonance may exist over that lung;" however, in patients with pulmonary agenesis, the state of the existing lung has stimulated so little investigation that there is no real agreement as to whether that lung may be expected to be emphysematous or hypertrophic. Smart" recorded the intrapleural pressures and bronchospirometric tracings of the existing lungs in two adult patients. The findings suggested hypertrophied rather than emphysematous organs, in contrast to the usual residual lung findings after pneumonectomy. Boyden" also studied the status of the remaining lung. In each of his three cases (right lung), the left lung exhibited such variants from the usual pattern as segmental deviations, extra lobes, and vascular anomalies. Roentgenographic examination of the chest usually shows the heart and medias-

Diseases of the Chest

tinum to be shifted to the affected side l 4.3 1 and a dense homogeneous shadow on that side." The shadow may represent fluid, fatty tissue, or persistent thymus, which, with the shifted mediastinum, sometimes helps to occupy the otherwise empty pleural cavity. The diaphragm on the affected side is usually elevated, and, characteristically, the contralateral lung is herniated across the midline. The bony thorax may be symmetrical, or the interspaces on the involved side may be narrowed because of concomitant scoliosis. On fluoroscopic study, the motion of the affected side may be limited, although respiratory excursions are normal in some patients. On pulmonary function tests, a significant reduction in maximum breathing capacity is evident, as well as a moderate to slight diminution in vital capacity. Near-normal values in oxygen consumption and alveolar perfusion are generally reported. In 1937, Hurwitz and Stephens" recommended bronchoscopy as the only really accurate means for diagnosis, and in 1938 Formijne" made the diagnosis in a 19-yearold female patient by that method. By bronchoscopic examination the presence and character of the bronchi can be determined. Bronchographic study will serve to outline the tracheobronchial tree and to show the bronchial distribution in the existing lung, as well as the amount of herniation. Conspicuous herniation of the lung through the mediastinum to the opposite side is sometimes found," More recently, angiocardiography became valuable in the diagnosis of pulmonary disorders. A preoperative diagnosis was successfully made by angiocardiographic examination as early as 1942;14 however, it was not until 1950 when Ingram" and associates published a paper on its value that this diagnostic means was really appreciated. The angiocardiogram gives information as to the position of the heart and the distribution of the pulmonary vessels. At the same time, associated congenital

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PULMONARY AGENESIS

malformations of the heart and great vessels may be discovered by angiocardiographic examination." DIFFERENTIAL DIAGNOSIS

To establish a definitive diagnosis of pulmonary agenesis, a number of conditions must be differentiated. In newborns, agenesis may resemble atelectasis. In older children, enlargement of the thymus may occasionally be a source of confusion, especially if the thymic shadow is unilateral. In young children, enlargement of the mediastinal nodes after whooping cough or pneumonia, or secondary to mediastinal or bronchial cystic development, may result in persistent pulmonary collapse. This circumstance may cause diagnostic difficulty or the presumption of agenesis. Bronchiectasis with atelectasis can also simulate agenesis of the lung. Patients who have undergone pneumonectomy could, possibly, confuse the inexperienced diagnostician. A complete block by tumor of one of the main bronchi could also be mistaken for agenesis. Differentiation between agenesis and persistent massive atelectasis, however, is of prime importance." Routine chest x-ray films are often misleading, since mediastinal shift and herniated normal lung are noted in both conditions. Furthermore, the detection of breath sounds on the affected side does not disprove agenesis, as the hyperdistention and herniation across the mediastinum may produce nearly normal physical signs on the side of the absent lung." On careful examination, however, the examiner will usually be able to detect diminution of sounds or absence of them in the lower areas of the affected thoracic cavity. PROGNOSIS

Agenesis, unless complicated by other anomalies, is not of itself necessarily incompatible with normal living. An increasing number of patients are continuing normal existence after pneumonectomy." A patient with one lung does not, however, withstand respiratory infections successfully,

and, in such a patient, bronchopulmonary complications often become very serious. Almost 50 per cent of the patients whose histories are recorded died in the first five years of life (generally from pulmonary infection), and about 20 per cent in the perinatal period.II Another obvious factor in the high infant mortality rate is the common coexistence of cardiovascular anom· d by ales. I· 11.18.24.21.33.11.'" I n th e cases reviewe Valle," 45 (37.5 per cent) had some associated congenital cardiovascular fault. An interesting and rare cause of death was reported by Thomas and Boyden," and, since then, by other investigators. Thomas and Boyden's patient with pulmonary agenesis died from aspiration of a foreign body. In another unusual case in which Siamese twins were successfully separated surgically, the nonviable twin had hypoplasia of the left lung, total absence of the right, and the right pleural space was obliterated .... CASE 1 .~ three-pound, white, infant of seven months' gestation was delivered by Caesarean section on June 16, 1949. The mother was 42 years of age and was eclamptic. The infant did not breathe spontaneously at birth and was cyanotic. With passage of an intratracheal catheter, a small amount of watery fluid was aspirated. There was no vomiting, convulsions or twitching. In the heart sounds, no abnormalities were audible. A few scattered coarse rales were heard over both of her lung fields, but were more notable on the right side where there was also some diminution of the breath sounds. About one week later there was only slight improvement in the infant's condition. Respirations then became irregular. She became hard to arouse and had obvious cyanosis of the lips, hands, and feet. After an uneven course for two months she appeared for a time to respond well; however, on August 29, 1949, she died suddenly and unexpectedly. A small amount of bloody, frothy fluid extruded from the mouth and nose; the lips and feet were definitely cyanotic; and the cause of death was believed to be atelectasis. At necropsy, these major findings were noted: 1. Congenital absence of the right middle lobe of the lung (as evidenced by total absence of the middle lobe bronchi). 2. Acute bilateral hemorrhagic interstitial pneumonia.

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3. Pulmonary edema. 4. The left common carotid artery originated from the innominate artery. 5. Prematurity. CASE

2

A 28-year-old white physician had known agenesis of the left lung since the age of five years, at which time his physician-father surveyed his family with some newly acquired x-ray equipment and made the diagnosis. After this discovery, the patient had a complete examination. Bronchoscopic and bronchographic studies showed the left main bronchus to end in a blind pouch. In the history was included a questionable episode of acute respiratory tract infection when he was six months of age. In grade school, he had bronchitis of about two months duration. Later, he was active in track and other athletic activities in school. At the age of 18, the patient began to smoke. He smoked cigarettes for about six years, after which he began to smoke cigars. At the present time, he smokes about five cigars a day. The physician-patient states that he has never been incapacitated by his condition and is well able to withstand the physical demands of an active surgical training program. His weight is now 160 pounds, and his height is six feet. On examination of the chest, flattening of the left chest wall, decreased expansion on the left side, deviation of the trachea to the left, audible heart sounds in the left chest basally, and dullness to percussion in the lower half of the left chest are discernible. The upper half of the left chest and sternum are resonant to percussion. Roentgenograms of the chest confirm the clinical findings and show herniation of the right lung across the midline. 3 A 13-month-old white boy was first hospitalized at the age of three weeks because of vomiting and possible hydrocephalus. At the age of two and one-half months, a right inguinal hydrocele had been found, and the baby was discharged to be readmitted in one month. He did not return until he was readmitted at the age of five months for recurrent pneumonia with heavy breathing and cyanosis. On physical examination at this time the pharynx was found to be hyperemic. His head was large and symmetrical, with patent fontanella and widened sutures. The liver was palpable to three centimeters below the right costal margin. Moderately severe respiratory excursions were diminished on the right side. Breath sounds were distant on the right, but loud on the left. Moist rales and ronchi were heard over both lung fields. The left lung was tympanitic to percussion and the right CASE

Diseases of the Chest

DENNIS M. L. ROSENBERG

No

heart murmurs were heard lung was dull. and the apex beat was in the right parasternal area. The impression at this time was that the child had ( I) hydrocephalus, (2) atelectasis of the right lung with mediastinal shift, and (3) bilateral pneumonia. A series of chest x-ray films were made that showed a narrowing of the right rib spaces, the heart shadow in the right chest, opacity of the right upper lung field, mediastinal shift to the right, marked compensatory emphysema of the left lung with anterior herniation into the right hemithorax, and normal aeration of the right lower lobe. Hemivertebrae were noted in the mid-thoracic area. On bronchographic examination, the left bronchial tree was normal, but on the right there was dye in the lower lobe only. There was no dye in the upper and middle lobes. Indeed, there was no evidence that these lobes existed. The findings were consistent with agenesis of the right upper and middle lobes. Right axis deviation was demonstrable on electrocardiographic study, indicative of myocardial disease and, probably, of left ventricular' hypertrophy. He was treated with antibiotics and was discharged with instructions to remain on antibiotic therapy. He was readmitted on June 4, 1955, with a recurrent respiratory infection and was treated successfully. His next hospitalization was on December 1, 1955. Again, he had a respiratory infection and operative treatment was advised. Physical and laboratory findings were unchanged from those of the previous admission. Surgical intervention was refused and the child has not been seen since. SUMMARY

Congenital absence or deficiency of pulmonary tissue is a rare condition, but it is not as uncommon as it was once presumed to be. Currently, with improved diagnostic means and augmented knowledge of the condition, agenesis is diagnosed with sufficient frequency to justify consideration in the differentiation of obscure or puzzling pulmonary conditions. The anomaly is not incommensurate with nonnallife expectation unless associated defects or malformations make survival impossible. Heightened susceptibility to respiratory infections or vascular incompetence is the major hazard. The histories of three patients illustrate some of the findings that may be expected, concomitantly, with agenesis of the lungs.

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PULMONARY AGENESIS

RESUMEN

ZUSAMMENFASSUNG

La ausencia congenita 0 la deficiencia del tejido pulmonar es rara pero no tan poco comun como antes se presumia, Actualmente con los medios de diagn6stico mejorados y un conocimiento mayor de esa posibilidad, la agenesia se diagnostica con suficiente frecuencia para justificar su consideraci6n en el diagn6stico diferencia en afecciones obscuras. La anomalia no afecta considerablemente la esperanza normal de vida a menos que haya otros defectos 0 malformaciones que hagan la sobrevida imposible. El mayor peligro consiste en una mayor suseeptibilidad a las infecciones respiratorias 0 las deficiencia vasculares. Estas constituyen el mayor peligro. Las historias de tres enfermos ejemplifican algunos de los hallazgos susceptibles de esperarse en el caso de la agenesia pulmonar.

Congenitales Fehlen oder Mangel an Lungengewebe ist ein seltener Umstand, aber er ist nicht so ungewohnlich wie vordem unterstellt wurde. Gegenwirtig und mit den verbesserten diagnostischen Moglichkeiten sowie groj3erer Kenntnis des Zustandbildes wird die Aplasie geniigend oft diagnostiziert und rechtfertigt ihre Anwendung bei der Differenzierung unldarer oder schwieriger pulmonaler Verhaltnisse. Die Mif3bildung ist nicht unvereinbar mit normaIer Lebenserwartung, sofem nieht damit verkniipfte Defekte oder Fehlbildungen ein Weiterleben unmoglich Macht. Die Hauptgefahr besteht in der erhohten Empfanglichkeit gegeniiber respiratorischen Infektionen oder mangeloder Gefaf3versorgung. Die Krankengeschichten von 3 Fallen erlautern einige der Befunde , mit denen man gleichzeitig mit einer Lungenaplasie rechnen mujl,

Complete reference list will a/J/Jear in

,h.

reprin's.

BALLISTOCARDIOGRAM AND AGING A cllnlcally adaptable. ultra-low frequency acceleration ballistocardiograph that met all theoretic considerations of biophysical design was used by Moss to evaluate the cardiovascular aging process In 307 overtly healthy men aged 18 to 54. The Initial appearance of accelerated cardiovascular aging (grade I abnormallty) was present on the ballistocardiogram In 16 per cent of the population by age 35. A more severe degree of aging (grade II) was evident in 16.5 per cent of the Individuals by age 50. There was a rather constant attack rate

for the Initial development of an abnormal ballistocardiogram (grade I) during the ?D to 39 age period, and an accelerated attack rate after age 40. The rate of conversion to a more severe grade of ballistocardiographic abnormallty Increased significantly In the fifth decade. The relationship between an abnormal ballistocardiogram. accelerated cardiovascular aging and coronary artery disease Is discussed.

Moss, A. J.: "Ballistocardiographic Evaluation of the Cardiovascular Aging Process," Circa/.lio1l, 23:434. 1961.

ALTERED HEMODYNAMICS IN THE PULMONARY CIRCULATION FOLLOWING REAERATION OF AN ATELECTATIC LUNG Experimental studies on dogs have clarified a number of pertinent points. Reaeratlon of a chronically atelectatic lung In the dog restores Its function partially. However, specific physiologic defects remain. They Include a variable but persistent loss of compllance, a marked Increase In pulmonary vascular resistance. a diminished pulmonary artery blood flow. and a concomitant decrease In oxygen uptake. Histopathologic changes have been noted In reaerated atelectatic animal lungs. A zone of subpleural hypolntlatlon was noted. Bronchiolar arteries exhibited formation of spurs or club-llke processes. In human beings with a reaerated chronically atelectatic lung, a slmllar partial restoration of function

with decrease In oxygen uptake has been reported by others. From the published reports In some patients, accordIng to available reports, the passage of time has favorably Influenced the function of reaerated atelectatlc lungs. It Is suggested that a complete functional evaluatlon of a patient with a reaerated lung after chronic atelectasis might pro~ erly Include bronchospirometry and an Investlgatlon of vascular reslatance and pulmonary compliance. LoNG, E. T .• ADAMS, W. E.• BaNFIILO, J. I. .• MntouCHI, T., RBI MANN, A. P.. AND NIGaO, S.: "Altered Hemodynamics in the Pulmonary Circulation followina B.euratioD of an Atelectatic Lun.... [, Tho,••,,11 C.,lIio •• S.,g., 40: 640, 1960.