Diagnostic Puzzlers: Recurrent dyspnea, fever, and pneumonia in a 67-year-old woman

A 67-year-old woman was referred for evaluation of exertional dyspnea, with multiple episodes of fever, cough, and pneumonia. She had a long history of cough with sputum and had been admitted several times for exacerbations of chronic obstructive pulmonary disease and pneumonia. She received maintenance therapy with an ipratropium and albuterol combination, fluticasone, and salmeterol, but she continued to experience exertional dyspnea, with an average of 5 or 6 exacerbations and 2 hospital admissions a year.

Pulmonary function testing done before presentation showed combined mild obstructive and moderate restrictive processes. Carbon monoxide-diffusing capacity was 36% of predicted. The patient had stopped smoking about 20 years ago; she had a 20-pack-year history. She had no history of heart failure, arrhythmia, hemoptysis, leg swelling, or deep venous thrombosis. Her weight and appetite were stable. She had 3 adult children; her pregnancies had been without complications.

Physical examination revealed a well-nourished, mildly tachypneic (respiration rate, 20 breaths per minute) woman with a temperature of 37.4ºC (99.3°F), heart rate of 98 beats per minute, and blood pressure of 110/65 mm Hg. There was no finger clubbing or lymphadenopathy.

Chest examination revealed decreased air entry over both lung fields, with a mildly prolonged expiratory phase but no crackles, wheezes, or rhonchi. The cardiovascular examination was notable for a loud P₂, grade 3/6 holosystolic murmur, most easily heard over the right fourth intercostal space. The murmur increased in intensity with inspiration.

Results of laboratory tests were normal. However, analysis of arterial blood gases on room air showed a pH of 7.45, a PO₂ of 58 mm Hg, a PCO₂ of 39 mm Hg, and a bicarbonate level of 27 mmol/L. The alveolar-arterial oxygen gradient was 41 mm Hg.

A chest radiograph was obtained (Figure 1).

What is the likely diagnosis? How would you proceed?

Recurrent dyspnea, fever, and pneumonia in a 67-year-old woman: The chest radiograph demonstrated hypovascularity and reduced size of the left lung (Figure 1). Other findings included a small hilum, hyperlucency, and a mediastinal shift toward the left lung.

A contrast CT scan of the chest (for evaluation of pulmonary embolism) demonstrated the absence of the left main pulmonary artery and confirmed the chest radiographic findings of the small hilum and the hyperlucency (Figure 2). Echocardiography confirmed the suspected pulmonary hypertension (pulmonary artery systolic pressure was 52 mm Hg) and showed moderate tricuspid regurgitation with no other intracardiac abnormalities. The diagnosis was congenital unilateral absence of a pulmonary artery (UAPA).

Discussion

The first report of UAPA was published in 1868; the first review of 98 cases, of which 32 were isolated UAPA, was published in 1962.¹ UAPA is also referred to as "proximal interruption of the pulmonary artery," because in some cases, surgical dissection reveals an incompletely developed pulmonary artery at the level of the hilum. Agenesis of the right pulmonary artery results from a lack of development of the right sixth aortic arch. Intrapulmo- nary vessels and the distal portion of the right pulmonary trunk often develop normally and receive their blood supply from bronchial vessels.² This results in a small hypovascular right lung.

Absence of the right pulmonary artery occurs more frequently than absence of the left pulmonary artery and may be associated with patent ductus arteriosus. Absence of the left pulmonary artery often is associated with other cardiovascular abnormalities, such as tetralogy of Fallot, right aortic arch, patent ductus arteriosus, and septal defects.

Because many patients with UAPA are asymptomatic, the prevalence of UAPA is difficult to establish. Some reports state that 30% of patients are asymptomatic.^3,4

In a retrospective analysis of 108 patients with UAPA who did not have associated cardiac anomalies, 14 were asymptomatic.⁵ Most patients had manifestations such as frequent pulmonary infections (37%), dyspnea or limited exercise tolerance (40%), or hemoptysis (20%). Pulmonary hypertension was present in 44% of the patients. In 63%, the right pulmonary artery was absent. Surgical procedures were performed in 17% of patients, and the overall mortality rate was 7%.⁵

In the 14 asymptomatic patients, the diagnosis of UAPA was made after abnormal findings were detected on a chest radiograph, which had been obtained for the following reasons: workup for tuberculosis, a routine chest radiograph before induction into the army, routine examination before surgery, and evaluation of scoliosis.⁵ Six patients received diagnoses after experiencing high-altitude pulmonary edema. In 3 of the patients, the diagnosis was made during or immediately after pregnancy, because of respiratory difficulties.

The patients underwent various studies, including CT scanning, MRI, and bronchography.⁵ A perfusion scan of the lungs was performed in 59% of patients, echocardiography in 34%, and cardiac catheterization in 90%.

The median patient age was 14 years (range, 0.1 to 58 years). One patient, a 58-year-old woman, had experienced episodes of fever, hemoptysis, and pulmonary infiltrates for almost 30 years before the diagnosis was made.^5,6 Another patient had had multiple protracted pulmonary infections since childhood and did not receive the final diagnosis of UAPA until the age of 39 years.^5,7

Various diagnostic studies are available for patients with UAPA. Chest radiography is usually performed as the first step. This may show an absent hilar shadow, a shrunken affected lung, and a shift of the mediastinal structures to the affected side.^5,6 In addition, the radiograph may demonstrate absence of the left or right pulmonary artery; ipsilateral, grossly diminished pulmonary vascular markings; a small hemithorax and intercostal bone space; ipsilateral cardiac and mediastinal displacement; ipsilateral hemidiaphragm elevation; and contralateral lung hyperinflation.^5,8

Echocardiography is a very helpful tool that may confirm the diagnosis and exclude other cardiovascular abnormalities. Other tools include MRI and high-resolution CT scanning, both of which are valuable in the evaluation of congenital heart defects.^5,9 These techniques can make the distal pulmonary arteries visible in patients with UAPA. High-resolution CT scanning also can detect bronchiectasis in patients with recurrent pulmonary infections.^3,5

Ventilation-perfusion scintigraphy may help delineate the anatomy of the affected side. When revascularization is proposed, cardiac catheterization is necessary and pulmonary venous wedge angiography can be used to detect hilar arteries.⁵

When pulmonary hypertension complicates UAPA, revascularization of the side with the absent artery can lead to improvement. In many cases, an identifiable artery at the hilum may be used for revascularization.^5,10 In postmortem studies and in surgical studies, hilar arteries usually are found.¹⁰

If revascularization is not feasible, or when pulmonary hypertension does not improve, therapeutic measures for primary pulmonary hypertension may be helpful. Long-term vasodilator therapy may improve survival in patients with primary pulmonary hypertension and in those with pulmonary hypertension secondary to congenital heart disease.^5,11 Massive hemoptysis is treated by selective embolization of the systemic collaterals,^5,12 or even by pneumonectomy of the affected side.^5,13

The overall mortality rate associated with UAPA is 7%.⁵ However, the development of pulmonary hemorrhage or pulmonary hypertension may affect long-term survival. Pulmonary hypertension can have devastating effects, especially when it develops during pregnancy.^5,14 In the above-mentioned review, 1 of the 3 patients with pulmonary hypertension died during pregnancy.⁵ The high mortality rate has led some to recommend preventing pregnancy or terminating it at an early stage in patients with a history of pulmonary hypertension.¹⁵ Therapy may include treatment with vasodilators, such as nifedipine, and continuous nitric oxide inhalation.¹⁶

Our case is unique in that the patient was older than patients in other reported cases of UAPA and had had 3 full-term pregnancies with no significant complications.

Case and photographs courtesy of Dr Amro Al-Astal and Dr Suns Yoon of the division of pulmonary, critical care, and sleep medicine at the Medical College of Ohio, Toledo.

References:

REFERENCES

1. Pool PE, Vogel JH, Blount SG Jr. Congenital unilateral absence of a pulmonary artery. The importance of flow in pulmonary hypertension.

Am J Cardiol.

1962;10:706-732.
2. Catala FJ, Marti-Bonmati L, Morales-Marin P. Proximal absence of the right pulmonary artery in the adult: computed tomography and magnetic resonance findings.

J Thorac Imaging.

1993;8:244-247.
3. Bouros D, Pare P, Panagou P, et al. The varied manifestation of pulmonary artery agenesis in adulthood.

Chest.

1995;108:670-676.
4. Arriero JM, Gil J, Martin C, et al. Unilateral absence of a pulmonary artery: congenital disease or embolic occlusion?

Eur Respir J.

1991;4:1299-1300.
5. Ten Harkel AD, Blom NA, Ottenkamp J. Isolated unilateral absence of a pulmonary artery: a case report and review of the literature.

Chest.

2002;122:1471-1477.
6. Krall WR, Ploy-Song-Sang Y. Unilateral pulmonary artery aplasia presenting with chest pain and pleural effusion.

South Med J.

1980;73:2332-2336.
7. Scheuch RW, Simon-Gabor M, Weinberg HR, Eisenberg H. Left pulmonary artery agenesis.

N Y State J Med.

1988;88:200-201.
8. Lin YM, Liang KW, Ting CT. Unilateral pulmonary artery agenesis with presentation of hemoptysis: a case report.

Zhonghua Yi Xue Za Zhi (Taipei).

1999;62:644-647.
9. Rebergen SA, de Roos A. Congenital heart disease. Evaluation of anatomy and function by MRI.

Herz.

2000;25:365-383.
10. Sotomora RF, Edwards JE. Anatomic identification of so-called absent pulmonary artery.

Circulation.

1978;57:624-633.
11. Barst RJ, Maislin G, Fishman AP. Vasodilator therapy for primary pulmonary hypertension in children.

Circulation.

1999;99:1197-1208.
12. Rene M, Sans J, Dominguez J, et al. Unilateral pulmonary artery agenesis presenting with hemoptysis: treatment by embolization of systemic collaterals.

Cardiovasc Intervent Radiol.

1995;18:251-254.
13. Mehta AC, Livingston DR, Kawalek W, et al. Pulmonary artery agenesis presenting as massive hemoptysis--a case report.

Angiology.

1987;38(1 pt 1):67-71.
14. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 4--1999. A 38-year-old woman with increasing pulmonary hypertension after delivery.

N Engl J Med.

1999;340:455-464.
15. Weiss BM, Zemp L, Seifert B, Hess OM. Outcome of pulmonary vascular disease in pregnancy: a systematic overview from 1978 through 1996.

J Am Coll Cardiol.

1998;31:1650-1657.
16. Lust KM, Boots RJ, Dooris M, Wilson J. Management of labor in Eisenmenger syndrome with inhaled nitric oxide.

Am J Obstet Gynecol.

1999;181:419-423.