Utility of Salivagram in Pulmonary Aspiration in Pediatric Patients: Comparison of Salivagram and Chest Radiography

Transcription

1 Pediatric Imaging Original Research Drubach et al. Salivagram in Pulmonary Aspiration Pediatric Imaging Original Research Laura A. Drubach 1 David Zurakowski 2 Edwin L. Palmer, III 3 Donald A. Tracy 4 Edward Y. Lee 5 Drubach LA, Zurakowski D, Palmer EL III, Tracy DA, Lee EY Keywords: chest radiography, pediatric patients, pulmonary aspiration, salivagram DOI: /AJR Received February 22, 2012; accepted after revision May 8, Department of Radiology, Division of Nuclear Medicine, Children s Hospital Boston and Harvard Medical School, Boston, MA. 2 Department of Anesthesia, Division of Biostatistics, Children s Hospital Boston and Harvard Medical School, Boston, MA. 3 Department of Radiology, Division of Nuclear Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA. 4 Department of Radiology, Division of Thoracic Imaging, Children s Hospital Boston and Harvard Medical School, 300 Longwood Ave, Boston, MA Address correspondence to E. Y. Lee (edward.lee@childrens.harvard.edu). 5 Department of Radiology, Children s Hospital Boston and Harvard Medical School, Boston, MA. AJR 2013; 200: X/13/ American Roentgen Ray Society Utility of Salivagram in Pulmonary Aspiration in Pediatric Patients: Comparison of Salivagram and Chest Radiography OBJECTIVE. The purpose of our study was to correlate the results of the radionuclide salivagram with the corresponding chest radiography findings on patients being evaluated for salivary aspiration to determine the utility of the salivagram. MATERIALS AND METHODS. We identified 222 patients younger than 21 years who underwent salivagram and chest radiography within 3 months of each other. Salivagrams were blindly interpreted by two readers and chest radiographs were blindly interpreted by two other readers. The kappa coefficient with 95% CI was used to measure the level of interobserver agreement. Multivariate logistic regression was applied to determine whether age, sex, and neurologic diagnosis were predictors of a positive salivagram, with the odds ratio used to estimate association. RESULTS. Interobserver agreement on salivagram interpretation was excellent (κ = 0.988; p < ; 95% CI, ). Interobserver agreement on chest radiography interpretation was excellent (κ = 0.905; p < ; 95% CI, ). The salivagram was positive for aspiration in 55 patients (25%). Chest radiography was positive in 54 patients (24%). When the interpretations of the salivagram (normal or abnormal) were compared with interpretations of the chest radiograph (normal or abnormal), there were 213 agreements and nine disagreements (intermethod agreement κ = 0.891; p < ; 95% CI, ). Independent of age (p = 0.80) and sex (p = 0.31), patients with a neurologic diagnosis had odds of a positive salivagram 5.6 times higher than other diagnoses (odds ratio = 5.6; 95% CI, ; p < ). CONCLUSION. Infants with abnormal findings on salivagrams also had a high rate of abnormal findings on chest radiographs, which may indicate that some of the lung disease may be due to aspirated saliva. Salivagrams may be useful in children at risk of aspiration to identify those in whom intervention may help minimize the consequences of aspiration. C hronic aspiration of saliva is a well-known cause of lung damage that often leads to multiple hospitalizations and extensive medical treatment for pulmonary infections and in some cases results in lung failure. It is frequently not recognized until significant lung damage has already occurred [1]. Diagnosis of the complications of salivary aspiration in pediatric patients are often challenging because symptoms can be quite varied and nonspecific, including chronic cough, wheezing, and choking [2]. Making an early and accurate diagnosis is of great clinical importance. If salivary aspiration can be detected early, lung damage might be prevented by using techniques to decrease the incidence of aspiration [3 7]. The full spectrum of clinical conditions that predispose patients to salivary aspiration has not been completely defined, but neuro- logically impaired children who have severe swallowing incoordination and reduced laryngopharyngeal sensitivity are at greater risk of saliva aspiration [8]. These are the patients in whom salivary aspiration is most commonly diagnosed. There are several other clinical predictors for the presence of aspiration, including developmental delay, reactive airway disease, and presence of chronic lung infections [9]. The presence of saliva aspiration can be visualized with the radionuclide salivagram, a safe and easily performed test that delivers very low radiation exposure to the patient. The salivagram has been found to be an effective method for detection of saliva aspiration [10 12]. In this study, we have evaluated the relationship between positive and negative salivagram results and the findings on the corresponding chest radiography for each patient who underwent a salivagram, a correlation that has not been previously described. AJR:200, February

2 Drubach et al. Material and Methods Patient Population The institutional review board approved this retrospective study and determined it to be in accordance with the regulations of the HIPAA privacy rule 45, Code of Federal Regulations parts 160 and 164, and that the criteria for waived patient authorization had been met. Salivagrams and chest radiographs of 222 patients under 21 years old who were consecutively examined between the years of 2003 and 2010 were retrospectively reviewed. Only those patients who underwent salivagram and chest radiography within 3 months of each other were included in this evaluation. The median time between the salivagram and the corresponding chest radiography on each patient was 1 day (interquartile range: 0 4 days). Salivagram Technique The salivagram was performed using 300 uci (11.1 MBq) of 99m Tc sulfur colloid. The radiopharmaceutical was administered orally as a small drop (approximately 100 µl) placed with a syringe either on the base of the patient s tongue or in a sublingual location while the patient was lying in a supine position on the imaging table. The patient was allowed to swallow naturally and posterior planar imaging of the mouth, chest, and upper abdomen was obtained. Continuous dynamic 30-second images were recorded for a total of 60 minutes, using a large-fov gamma camera with a high-resolution or ultrahigh-resolution low-energy collimator. The whole-body radiation absorbed dose to the patient for a salivagram is approximately 0.05 msv (5 mrem) [13] in contrast with a fluoroscopic barium swallow that delivers a radiation dose of 1.5 msv (150 mrem) [14]. Chest Radiography Technique Children < 2 years old underwent anteroposterior projection radiography performed with mobile radiography equipment (AMX 4, GE Healthcare) using high voltage, tube current, and exposure times at a 100-cm focus-film distance. Older children (2 21 years) underwent posteroanterior and lateral projection radiographs obtained with nonportable radiography equipment (Bucky Diagnost, Philips Healthcare) using high voltage, tube current, and exposure times at 180-cm focus-film distance. Either parents or radiologic technologists immobilized young children (1 6 years) for the anteroposterior, posteroanterior, and lateral projection radiographs. Older children (> 6 years) underwent the posteroanterior and lateral projection radiographs using standard standing position. The estimated effective radiation dose from posteroanterior and lateral chest radiograph is and msv, respectively, for pediatric patients in our institution. Fig. 1 Image from negative salivagram in 5-yearold girl shows activity in mouth, esophagus, and stomach. Image Interpretation Salivagram The salivagrams were reviewed by two board-certified nuclear medicine physicians with 15 years and 27 years of experience in nuclear medicine. Anonymized scans were reviewed independently in a randomized order. The readers were blinded to each other s interpretation and to the chest radiography findings and other clinical data. Any discrepancy between interpretations was resolved by consensus in a joint review session. The salivagram findings were considered positive if activity was visible lateral to the midline in the expected location of bronchi. The study was considered negative if there was only midline linear activity in the expected location of the esophagus (Fig. 1). The severity of aspiration was scored as grade 1 if the activity was only present in the location of main bronchi and grade 2 if activity was also present in the location of more peripheral bronchi ramifications (Fig. 2). Aspiration was scored as unilateral or bilateral and the side of aspiration noted. Chest radiograph All chest radiographs were reviewed by two board-certified radiologists, with 7 years and 25 years of experience in interpreting pediatric chest radiographs. Anonymized radiographs were reviewed independently in a randomized order. The readers were blinded to each other s interpretation, salivagram findings, and other clinical data. For cases in which there was a discrepancy between the two readers observations, the reviewers jointly reevaluated the cases to reach a consensus decision. All chest radiographs were reviewed using a PACS (Smart CR, Fujifilm Medical Systems). The reviewers first classified all chest radiographs as normal or abnormal on the basis of an assessment of the lungs. Subsequently, abnormalities were systemically characterized in the lungs. Lungs were evaluated for prominent peribronchial markings, consolidation, and bronchiectasis. The diagnosis of prominent peribronchial markings was made when there were coarse linear markings [15, 16]. A diagnosis of consolidation was made when there was an area of increased opacity that obscured the margins of vessels and airway walls, with or without air bronchograms [17]. Bronchiectasis was defined as bronchial dilatation, with or without associated bronchial wall thickening [17]. Lung abnormalities were subsequently evaluated for the anatomic location, distribution, and extent of abnormality. The anatomic distribution, location, and extent of the lung abnormalities were evaluated globally and categorized as unilateral or bilateral; involvement of upper, middle, or lower lung zones (defined as each zone comprising one third of the craniocaudal extent of the lungs on the frontal radiograph); and extent of abnormalities (defined as grade 1 with involvement of lungs 50% and grade 2 with > 50%) [18]. Statistical Analysis Interobserver agreement for readers of salivagrams and chest radiographs as well as consensus readings were determined using the chance-corrected kappa coefficient, where excellent agreement was represented by kappa values greater than 0.75 [19]. The McNemar test was used to assess systematic disagreement between consensus readings on salivagram examinations and chest radiography. Age and days between salivagram and chest radiography were summarized in terms of the median, interquartile range due to departure from normality. Simple binary proportions, including sex and diagnosis between positive and negative salivagram results, were compared using the Fisher exact test. Multivariate logistic regression was applied to determine whether age, sex, and neurologic diagnosis were predictors of a positive salivagram with the odds ratio used to estimate association [20]. Statistical analyses were performed using SPSS version Two-tailed values of p < 0.05 were considered statistically significant, with 95% CIs constructed around all kappa values (± 1.96 standard error) and odds ratios as a measure of precision. Power analysis indicated that a sample size of 220 patients would provide 90% power to estimate the population intraclass kappa coefficient between salivagram and chest radiography readings with a precision of 0.05 (nquery Advisor, version 7.0, Statistical Solutions) [21]. Results Study Cohort Of the 222 total patients, there were 120 boys (54%) and 102 girls (46%). The principal underlying clinical diagnosis was a neurologic disorder, such as cerebral palsy, epilepsy, developmental delay, hydrocephalus, 438 AJR:200, February 2013

3 Salivagram in Pulmonary Aspiration tients. Of the 55 positive salivagrams, 29 were classified as grade 1 and 26 were grade 2. Interobserver agreement on salivagram interpretation between the two readers was excellent. There was agreement of interpretation in 221 patients (99.5%), with both readers scoring negative in 167 patients and positive in 54 patients. The readers disagreed in only one patient (reader 1, negative; reader 2, positive). The resulting chance-corrected value of kappa was (p < ; 95% CI, ). There were 55 (25%) positive salivagrams on the basis of consensus reading. The additional information provided by the salivagram resulted in alteration of patient management in all 55 patients with a positive study. After a positive salivagram, 27 of 55 (49%) patients had the addition or a change in dosage of glycopyrrolate, a medication used to reduce oral secretions; eight of 55 (15%) patients had a procedure performed to decrease salivary formation (salivary gland botulinum toxin injections, excision of the salivary glands, salivary gland duct ligation, and laryngotracheal separation), and 20 of 55 (36%) patients had a change in the regimen of chest physical therapy and bronclodilators. and hypotonia in 140 patients (63%), with other chronic diseases in 82 (37%), such as chromosomal abnormalities, congenital cardiac defects, velocardiofacial syndrome, and other facial abnormalities. The median patient age was 2.3 years, with a range of 18 days to 19.6 years. The interquartile range was 1 8 years. The median time between salivagram and chest radiography studies was 1 day, with an interquartile range of 0 4 days (i.e., 50% of patients had their salivagram and chest radiography within 4 days of each other). A total of 20 patients had a difference of greater than 1 month but less than 3 months between salivagram and chest radiography studies. Although there were no differences in age or sex between positive and negative salivagrams, patients with neurologic diagnoses had higher rate of positive salivagrams compared with other diagnoses. Multivariate logistic regression confirmed that independent of age (p = 0.80) and sex (p = 0.31), a neurologic diagnosis was associated with a significantly higher odds of a positive salivagram (odds ratio, 5.6; 95% CI, ; p < ). A Fig. 2 Images from positive salivagrams show activity that extends lateral to midline position of esophagus. A, Salivagram image in 12-year-old girl shows proximal bronchial uptake, classified as unilateral grade 1 aspiration. B, Salivagram image in 16-year-old boy shows activity extending more peripherally within bronchi bilaterally, classified as bilateral grade 2 aspiration. Salivagram Findings The salivagram was positive for aspiration in 55 (25%) patients, with a unilateral aspiration in 11 (5%) patients and bilateral aspiration in 44 (20%) patients. If unilateral aspiration was present, it occurred on the right side in nine (82%) patients and on the left in two (18%) pa- B Chest Radiography Findings The most common finding on chest radiography was consolidation in 37 patients (68%) followed by prominent peribronchial markings in 16 patients (30%) and bronchiectasis in one patient (2%). Among the 54 patients with positive chest radiography, there were 135 lobes involved. The most common lobe involved was the left lower lobe in 50 patients (37%), followed by the right lower lobe in 46 patients (34.1%), right upper lobe in 16 patients (11.9%), right middle lobe in eight patients (5.9%), left lingula in eight patients (5.9%), and left upper lobe in seven patients (5.2%). The interobserver agreement on chest radiography interpretation between the two readers was excellent. There was agreement of interpretation in 214 (96%) patients, with both readers scoring negative in 162 patients and positive in 52 patients. The readers disagreed in eight patients (reader 1 negative and reader 2 positive in six cases; reader 1 positive and reader 2 negative in two cases). The resulting chancecorrected kappa value was (p < ; 95% CI, ). There were 54 (24%) chest radiography examinations with positive findings on the basis of consensus reading. Agreement Between Salivagram and Chest Radiographic Findings When the consensus readings of the salivagram (normal or abnormal) were compared with consensus interpretations of the corresponding chest radiograph (normal or abnormal), there were 213 (96%) agreements and nine (4%) disagreements (Table 1). In 163 (73%) patients, the salivagram was negative for aspiration and the chest radiograph showed no abnormality. In 50 (23%) patients, the salivagram showed aspiration and the chest radiograph was abnormal TABLE I: Comparisons of Salivagram and Chest Radiography Findings on Basis of Consensus Results Chest Radiography Findings Normal Salivagram Findings Abnormal Total Normal Abnormal Total Note Excellent agreement: κ = 0.891; 95% CI ; and p < Overall agreement between methods: 213/222 = 95.9%. AJR:200, February

4 Drubach et al. (Fig. 3). Evaluation of the intermethod agreement between salivagram and chest radiography consensus readings showed chance-corrected values of κ = 0.891; p < ; 95%; and 95% CI, McNemar test revealed no significant systematic disagreement between the results of the two methods (p = 0.99). In five (2%) patients, the salivagram showed aspiration, but the chest radiograph was normal. Further examination of these patients showed that the median age was 6 months, with a range of 18 days to 1 year. This was significantly younger than the overall patient group age, which had a median age of 2.3 years. In four (2%) patients, the salivagram showed no aspiration, but the chest radiograph was abnormal. Among the 50 patients in whom consensus readings on both salivagram and chest radiography were positive, salivagram findings indicated 27 mild and 23 severe grades, whereas chest radiography findings indicated 33 mild and 17 severe grades. Discussion Salivary aspiration occurs when disorders of the swallowing mechanism result in pulmonary aspiration of normal saliva, a process that the radionuclide salivagram can document [10, 20 24]. It is important to differentiate pulmonary aspiration of saliva from the more commonly considered aspiration that may follow gastroesophageal reflux. Salivary aspiration can occur even in the absence of reflux, and the presence or absence of the latter is not directly relevant to its diagnosis. It has been previously shown that evaluations of lung aspiration by performing a gastroesophageal reflux study either scintigraphically (milk study) or with a barium A Fig. 3 Salivagram and chest radiography in 18-month-old girl with global developmental delay who presented with increasing oxygen requirements. A, Salivagram shows bilateral aspiration. B, Frontal chest radiograph shows multifocal consolidation bilaterally. B swallow are not sensitive for the detection of aspiration and that the salivagram shows pulmonary aspiration more frequently than does either of these studies [25, 26]. The salivagram is a simple procedure that involves very little radiation exposure to the patient. The study relies on the patient s natural swallowing physiology by putting a small drop of tracer in the mouth and following the transit of that activity to determine whether tracer is aspirated into the bronchi. Unlike other diagnostic procedures, the salivagram does not involve a nonphysiologic bolus administration of contrast agent. Because there is no IV injection of tracer and because only about 300 μci (11 MBq) is administered orally, radiation dosimetry of the technique is very favorable, with a typical patient absorbed dose of only about 0.05 msv (5 mrem) [13]. The very low radiation exposure of the procedure makes it feasible to perform the examination on a repeated basis if the patient shows worsening respiratory findings. Our study expands on previous smaller studies [10, 24] in which the incidence of positive salivagram findings was assessed in a high-risk patient population with a history of lung infections. We evaluated the direct correlation between the findings of the salivagram and the corresponding chest radiography, something that was not performed in the past. We showed that an abnormal salivagram for salivary aspiration was associated with the presence of an abnormality on the corresponding chest radiography performed within 3 months of each other in 50 of 55 (91%) patients. The salivagram is thus capable of identifying those patients who will have aspiration that can cause structural lung changes that are visible radiographically. Our study further shows that any aspiration that is visualized by salivagram is strongly correlated with chest radiography abnormalities and therefore likely to be clinically significant. In our series, a normal salivagram strongly correlated with the presence of a normal radiograph, even in this high-risk population. When the salivagram is normal, we believe that further radiographic evaluation is not routinely necessary. We found no correlation between the magnitude of aspiration shown by salivagram (grade 1 or grade 2) and the extent of chest radiography abnormality. Only the presence or absence of aspiration correlated with radiographic findings. A possible limitation to our study is that the grading system that we used (aspiration in the proximal bronchi vs peripheral bronchi) is based on imaging findings and might not be physiologically meaningful. There were five patients who had a positive salivagram for aspiration but negative chest radiography. Because these patients were significantly younger than the group as a whole, it would be intriguing to speculate whether sufficient time to produce radiographically evident lung changes might not have elapsed in this particular group. Previous studies have only described the number of positive salivagram evaluations in high-risk populations. To our knowledge, there are no prior reports of direct correlation between salivagram and radiographic imaging findings in each specific patient. Because there is no reference standard to verify the presence of aspiration, it is impossible to determine the actual sensitivity of the salivagram. The strong correlation between salivagram results and chest radiographic findings that we describe, however, indicates that this procedure is a valuable clinical tool to determine both the presence of aspiration and the likelihood of identifiable radiographic consequences. In our population, the additional information provided by an abnormal salivagram resulted in a change in clinical management in all patients. Some of our patients had only a single frontal chest radiograph and this could be seen as a potential limitation of our methodology. This practice, however, is in accordance with our current standard of practice. We believe that if a salivagram is performed early in the clinical evaluation of children with complex medical histories that are associated with a risk of salivary aspiration it could allow the treating physician to institute therapies to 440 AJR:200, February 2013

5 Salivagram in Pulmonary Aspiration eliminate salivary aspiration, therefore preventing or minimizing the subsequent development of lung disease. 8. Hussein I, Kershaw AE, Tahmassebi JF, Fayle SA. The management of drooling in children and patients with mental and physical disabilities: a lit- 17. Hansell DM, Bankier AA, MacMahon H, McLoud TC, Muller NL, Remy J. Fleischner Society: glossary of terms for thoracic imaging. Ra- References 1. Boesch RP, Daines C, Willging JP, et al. Advanc- erature review. Int J Paediatr Dent 1998; 8: Simons JP, Rubinstein EN, Mandell DL. Clinical predictors of aspiration on radionuclide saliva- diology 2008; 246: Lee EY, McAdam AJ, Chaudry G, Fishman MP, Zurakowski D, Boiselle PM. Swine-origin influ- es in the diagnosis and management of chronic pulmonary aspiration in children. Eur Respir J 2006; 28: Owayed AF, Campbell DM, Wang EE. Underlying causes of recurrent pneumonia in children. Arch Pediatr Adolesc Med 2000; 154: Jongerius PH, van Limbeek J, Rotteveel JJ. Assessment of salivary flow rate: biologic variation and measure error. Laryngoscope 2004; 114: Jongerius PH, van den Hoogen FJ, van Limbeek J, Gabreels FJ, van Hulst K, Rotteveel JJ. Effect of botulinum toxin in the treatment of drooling: a controlled clinical trial. Pediatrics 2004; 114: Mier RJ, Bachrach SJ, Lakin RC, Barker T, Childs J, Moran M. Treatment of sialorrhea with glycopyrrolate: a double-blind, dose-ranging study. Arch Pediatr Adolesc Med 2000; 154: Stern Y, Feinmesser R, Collins M, Shott SR, Cotton RT. Bilateral submandibular gland excision with parotid duct ligation for treatment of sialorrhea in children: long-term results. Arch Otolaryngol Head Neck Surg 2002; 128: Takamizawa S, Tsugawa C, Nishijima E, Muraji T, Satoh S. Laryngotracheal separation for intractable aspiration pneumonia in neurologically impaired children: experience with 11 cases. J Pediatr Surg 2003; 38: grams in children. Arch Otolaryngol Head Neck Surg 2008; 134: Bar-Sever Z, Connolly LP, Treves ST. The radionuclide salivagram in children with pulmonary disease and a high risk of aspiration. Pediatr Radiol 1995; 25(suppl 1):S180 S Levin K, Colon A, DiPalma J, Fitzpatrick S. Using the radionuclide salivagram to detect pulmonary aspiration and esophageal dysmotility. Clin Nucl Med 1993; 18: Cook SP, Lawless S, Mandell GA, Reilly JS. The use of the salivagram in the evaluation of severe and chronic aspiration. Int J Pediatr Otorhinolaryngol 1997; 41: Treves ST, Baker A, Fahey FH, et al. Nuclear medicine in the first year of life. J Nucl Med 2011; 52: Wall BF, Hart D; National Radiological Protection Board. Revised radiation doses for typical x-ray examinations. report on a recent review of doses to patients from medical x-ray examinations in the UK by NRPB. Br J Radiol 1997; 70: Donnelly LF. Chest. In: Donnelly LF, ed. Diagnostic imaging: pediatrics. Salt Lake City, Utah: Amirsys, 2005: Bramson RT, Griscom NT, Cleveland RH. Interpretation of chest radiographs in infants with cough and fever. Radiology 2005; 236:22 29 enza a (H1N1) viral infection in children: initial chest radiographic findings. Radiology 2010; 254: Kundel HL, Polansky M. Measurement of observer agreement. Radiology 2003; 228: Katz MH. Multivariable analysis: a practical guide for clinicians and public health researchers, 3rd ed. New York, NY: Cambridge University Press, Block DA. Kraemer HC. 2 x 2 kappa coefficients: measures of agreement or association. Biometrics 1989; 45: Baikie G, Reddihough DS, South M, Cook DJ. The salivagram in severe cerebral palsy and ablebodied adults. J Paediatr Child Health Collier BD. Detection of aspiration: scintigraphic techniques. Am J Med 1997; 103(5A):135S 137S 24. Heyman S, Respondek M. Detection of pulmonary aspiration in children by radionuclide salivagram. J Nucl Med 1989; 30: Baikie G, South MJ, Reddihough DS, et al. Agreement of aspiration tests using barium videofluoroscopy, salivagram, and milk scan in children with cerebral palsy. Dev Med Child Neurol 2005; 47: Fawcett HD, Hayden CK, Adams JC, Swischuk LE. How useful is gastroesophageal reflux scintigraphy in suspected childhood aspiration? Pediatr Radiol 1988; 18: AJR:200, February