Adil Zamanı 1, Ayse Gul Zamanı 2
1 Department of Chest Diseases, Meram Medical Faculty, Selcuk University, Konya, Turkey
2 Department of Medical Genetics, Meram Medical Faculty, Selcuk University, Konya, Turkey
Correspondence to: Dr.Adil Zamani E-mail: zamaniad@yahoo.com
SMJ 2006 51(2): 54
Abstract
Swyer-James syndrome (SJS) is a rare disorder characterized radiologically by a unilateral hyperlucent lung. Although respiratory tract infections play an important role in the development of SJS , some cases have no documented history of repeated episodes of childhood respiratory infection . It has been suggested that some congenital factor(s) may contribute to the development of SJS. The purpose of this study was to investigate clinical and cytogenetic features of three patients with this syndrome. Diagnosis of SJS was first suspected based on admission chest radiographs. Chest computed tomography,ventilation-perfusion lung scintigraphy and pulmonary magnetic resonance angiography confirmed the diagnosis. Bronchiectases were revealed on the affected sides of all patients.In addition, two of them had asthma,and one patient had cor pulmonale. There was no bronchoscopic evidence of benign or malignant endobronchial obstruction. Bronchial mucosa cells(BMC) and peripheral blood lymphocytes(PBL) cultures were obtained from all patients. Cytogenetic analyses of these samples revealed normal karyotype in two patients. Due to bronchial candidiasis, cytogenetic analysis of BMC could not be performed in the remaining patient;however, his culture of PBL demonstrated a normal karyotype. In conclusion, other pulmonary disorders such as asthma,bronchiectasis, and fungal infection of the respiratory tract can be demonstrated in conjuction with the SJS. Although, normal karyotypes were demonstrated in our patients ,further cytogenetic studies are needed to elucidate the molecular basis of SJS.
Key words: Swyer-James syndrome, MacLeod's syndrome, bronchoscopy, cytogenetics, karyotype.
Swyer-James (MacLeod's) syndrome is a form of obliterative bronchiolitis characterized radiologically by a unilateral hyperlucent lung 1,2. This condition is quite rare occurring with a prevalence of 0.01% in 17,450 survey chest radiographs 3.
SJS is believed to be caused by injury of the immature lung mostly after an acute viral infection occuring during the first 8 years of life. Adenovirus, measles virus, influenza virus, respiratory syncytial virus, and mycoplasma have been implicated as possible causes for this condition 2,4. Analysis of bronchoalveolar lavage showed that there was an ongoing process with inflammatory characteristics in patients with SJS, several years after the original lung injury 4.
Although respiratory tract infection is regarded as the main causative factor for this syndrome, approximately 40% of cases have no documented history of repeated episodes of childhood respiratory infection 5,6. It has been suggested that some congenital factor(s) may contribute to the development of SJS 6. However,there is only anecdotal information about the genetics of this disorder 7, and to the best of our knowledge there are no publications dealing with cytogenetic aspects of SJS. Thus, the current study was designed to evaluate clinical and cytogenetic features of patients with this rare condition.
The clinical and cytogenetic studies were prospectively carried out in three patients who were admitted to the Selcuk University Hospital, Department of Chest Diseases. In addition to a detailed medical history and physical examination the following studies were performed for diagnosis of Swyer-James syndrome (SJS): (1) chest radiographs (inspiratory/expiratory) demonstrating a unilateral hyperlucency, a small hilum, and an air trapping on the affected side; (2) chest computed tomography(CT) demonstrating an increased radiolucency and decreased vascularity of the affected lung; (3) ventilation-perfusion lung scintigraphy (V/Q scan) showing a decrease or absence of perfusion and impaired ventilation in the affected lung (matched defect) 1,2 . In addition, all patients underwent contrast-enhanced three-dimensional pulmonary magnetic resonance (MR) angiography , flexible fiberoptic bronchoscopy,arterial blood gas (ABG) analysis, and pulmonary function tests(PFT). Moreover, serum samples were obtained for measurement of alpha1-antitrypsin (AAT). All ventilation–perfusion lung scans were performed using Tc-99m-DTPA (aerosolized) and Tc-99m-macro-aggregated albumin.
Fiberoptic bronchoscopy was performed by an Olympus bronchoscope ( model BF 1 T40; Olympus Co, Tokyo, Japan). After a thorough endoscopic inspection, bronchial washings and bronchial mucosa biopsy samples were taken from the main bronchus of the affected lung. The samples were sent immediately to the laboratories for bacteriologic, cytologic, and cytogenetic analyses .
Cytogenetic analyses of peripheral blood lymphocytes (PBL) and bronchial mucosa cells(BMC) cultures were performed according to previously published procedures 8-10. Twenty metaphase spreads obtained from PBL and BMC cultures of each patient were analysed, and karyotypes were reported according to the International System for Human Cytogenetic Nomenclature (ISCN) 11.
The clinical,laboratory, and cytogenetic findings of the patients are summarized in Table I. Diagnosis of SJS was first suspected based on admission chest radiographs. Three radiologic findings(unilateral hyperlucency,small hilum,and air trapping) , characteristic of this syndrome, were present in all patients. Two cases (No. 2 and 3) had left lung, and one had right lung involvement. To provide further confirmation of the diagnosis chest CT,V/Q scan and pulmonary MR angiography were performed. Unilateral hyperlucency and decreased vascularity of the affected side were present on the chest CT scans of all patients . Bronchiectases were found in all three patients on the affected side (Figure 1). V/Q scan demonstrated matched V/Q defects, and pulmonary MR angiography revealed a small pulmonary artery with a decrease in the size and number of its branches on the affected side of all three patients (Figure 2) .
There was no bronchoscopic evidence of benign or malignant endobronchial obstruction, and findings were consistent with bronchitis. Bronchial washings and bronchial mucosa biopsy cultures yielded Candida albicans in patient 2. The remaining patients' samples were negative for pathogenic microorganisms. Cytologic findings were unremarkable in all three patients.
ABG analyses revealed mild hypoxemia without hypercapnia (patients 1 and 3) and severe hypoxemia with hypercapnia(patient 2). Patient 2 was unable to perform spirometry because of his deteriorated condition. Pulmonary function tests of the two remaining patients demonstrated a decreased forced vital capacity, airflow obstruction, and a reduced diffusion capacity. AAT levels were found to be in the normal range in all patients.
Cytogenetic analysis of PBL cultures showed normal karyotype in all patients. Cultures of BMC revealed normal karyotypes in patients 1 and 3 . However, BMC culture obtained from the patient 2 grew C.albicans, and this was the reason for failure to perform a cytogenetic analysis.
The diagnosis of SJS is based mainly on roentgenographic and clinical findings . Plain chest radiographs typically reveal a hyperlucent area, a small hilum, and air trapping in the affected lung 12,13. All the above-mentioned radiologic findings were present in our patients. The left lower lobe involvement is more common than right lung (88% vs 25%, respectively)13. Two patients in this sudy had left-sided hyperlucency.
Chest CT scan is useful in detecting bilateral abnormalities and bronchiectasis.In addition, it is valuable in eliminating other diagnoses that can mimic unilateral hyperlucency, such as central bronchial obstruction,cysts, and vascular disease 2,12. Dynamic ultrafast high-resolution computed tomography (HRCT) can also be helpful in assessing pulmonary artery system, air trapping, and bronchiectasis 13. The frequency of bronchiectasis in patients with SJS varies between 38 and 70% 12,14. All three patients reported here had an evidence of bronchiectasis in the affected side.
Ventilation/perfusion (V/Q) lung scans show a decrease in lung perfusion and evidence of air trapping on wash-out ventilation scan on the affected lung ( matched defects)12. It has been suggested that a V/Q scan is more sensitive than a CT scan in detecting affected lung regions and superior in showing their extent and distribution 15.
Pulmonary angiography is now rarely used because CT or spiral CT angiography are usually sufficient for diagnosis of SJS 1. Another potentially promising noninvasive technique is the three-dimensional MR angiography, which can give clinicians a highly detailed anatomic information about the pulmonary artery system of patients with SJS. Moreover, this technique is free of radiation exposure, and angiography-related adverse effects,such as cardiac arrhythmia, endocardial injury, and vasovagal syncope 13. In the present study, pulmonary MR angiography clearly demonstrated a small pulmonary artery with a decrease in the size and number of its branches on the affected side of all three patients.
If an intrabronchial tumor is suspected, it is advisable to perform a diagnostic bronchoscopy 1,2,16.The predominant bronchoscopic finding revealed in our patients was bronchitis. In addition,one of them had bronchial candidiasis. This finding emphasizes the possible risk of respiratory tract fungal infection in patients with SJS. Long treatment with antibiotics or antibiotics and corticosteroids has been found to predispose to bronchial candidiasis in patients with chronic bronchitis or bronchiectasis 17.
Pulmonary function test results vary with the amount of affected lung, and may reveal a reduced vital capacity,some airflow obstruction, and a reduced gas diffusing capacity 1,2,7. Arterial blood gas analysis is usually unremarkable, but may be abnormal during exercise 1. Cases of unilateral hyperlucent lung associated with hypoxemia,pulmonary hypertension,and cor pulmonale presumably are the result of the subsequent development of airflow obstruction (with or without emphysema) in the contralateral lung 1. In this study,one of our patients had severe hypoxemia and cor pulmonale with poor response to treatment which led to his eventual death. The other two patients had reversible airflow obstruction due to asthma showing a good clinical response to treatment. Concomitant presence of asthma in patients with SJS has been reported previously 13.
The clinical course of SJS is mostly benign. The prognosis and severity of this disorder is variable and depends on the development of bronchiectasis and frequency of recurrent pneumonia 18,19. In this study, patients 1 and 3 have been followed up at regular intervals, and during a follow-up period of 20-30 months no remarkable events were observed. However, patient 2 died of respiratory failure approximately one-month after discharge. Surgical resection should be considered for those patients with serious infection, significant bronchiectasis, progressive dyspnea or life threatening hemoptysis 7,13,18,19.
Respiratory tract infections play an important role in the development of SJS, but repeated episodes of childhood respiratory infection has been documented approximately only in two third of the cases 5. It has been suggested that some possible congenital factor(s) may be involved in the development of SJS 6. Although a family history has been reported previously 7 , at the present , there are still insufficient genetic data of this disorder. To our knowledge karyotyping analysis of PBL and BMC has not been investigated in order to elucidate the chromosomal features in SJS. In the present study, we did not find any difference between chromosomal constitutions of PBL and BMC.
In conclusion, other pulmonary disorders such as asthma,bronchiectasis, and fungal infection of the respiratory tract can be demonstrated in conjuction with the SJS. An early diagnosis and a proper treatment of these disorders could have a beneficial impact on the long term prognosis of this syndrome. Although, normal karyotypes were demonstrated in our patients ,further cytogenetic studies are needed to elucidate the molecular basis of SJS.
Acknowledgements: The authors thank Dr.Yildiz Karabayir, Dr.Kerim Yesildag, and Assist.Prof.Gul Durakbasi for their technical assistance.
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