A 6-month-old previously healthy boy presented to the emergency department with a 2-day history of cough, wheeze, and increased work of breathing. The history and examination results were suggestive of bronchiolitis, and the patient was placed on a bronchiolitis protocol. He initially seemed to be responding to supportive care with nasal suctioning and supplemental oxygen only.
Several days elapsed, and the tachypnea and hypoxia persisted. The infant was additionally noted to be a slow breastfeeder and he exhibited a marginal failure to thrive (weight at fifth percentile). On hospital day 6, he was still requiring 0.2 L nasal cannula oxygen to maintain saturations of 92% and persistently maintained a respiratory rate in the 50s. Chest radiography revealed mild hyperexpansion and peribronchial cuffing consistent with bronchiolitis, and the results of viral testing were negative.
Does this case require patience or further testing?
Risk factors for severe bronchiolitis are well established, including prematurity; age <2 months; chronic lung, heart, and neurologic diseases; poor nutritional status; and environmental tobacco smoke exposure.1–3 Even in otherwise healthy infants, complicating factors may prolong or alter the typical clinical course in bronchiolitis, including swallowing dysfunction, impaired nutrition, and development of superimposed infections.
Small published series have demonstrated an increased risk of aspiration during the course of illness, reported in 60% of infants with bronchiolitis who underwent a videofluoroscopy swallow study. Thickening feeds demonstrated improvement in both aspiration and laryngeal penetration.4,5 A recent, retrospective study evaluated the associations of various clinical markers that could be attributed to any infant with bronchiolitis. Greater usage of supplemental oxygen, tachypnea, and decreased total caloric intake during the first 2 days of hospitalization were associated with prolonged hospital stay in infants <1 year of age with bronchiolitis.2
Impaired nutrition may prolong and/or increase the risk of complications and secondary infections in infants with bronchiolitis. Globally, the 4 key nutritional risk factors for acute lower respiratory tract infection include macronutrient undernutrition, low birth weight, zinc deficiency, and suboptimal breastfeeding.6 Maternal nutritional status and vitamin D deficiency have also been suggested to contribute.7
Because of the poor growth coupled with persistent tachypnea and hypoxia, a sweat chloride test was ordered as was a complete blood cell count to rule out anemia. An order for a purified protein derivative test was placed because of a history of frequent visits to a nursing home. The results of the sweat chloride and purified protein derivative tests were negative. Neutropenia, with an absolute neutrophil count of 600 (total white blood cell count 5000) was found on the results of the complete blood cell count, although it was attributed to transient, viral suppression when it resolved on 72 hours follow-up. Given a lack of findings to explain the persistent hypoxia, a modified barium swallow was obtained that showed mild dysphagia with thin liquids but no laryngeal penetration. These findings were felt to be consistent with a normal response to mild respiratory distress and not indicative of underlying pathology. An echocardiogram was obtained on hospital day 8 that showed only a small patent foramen ovale.
On hospital day 10 all symptoms persisted and a chest computed tomography (CT) scan was obtained showing a bilateral, diffuse, ground-glass infiltrate in an interstitial pattern which was read as worrisome for underlying chronic lung disease (Fig 1), but it was difficult to interpret in the setting of a presumed acute viral infection. Pulmonary consult was sought for bronchoscopy and Haemophilus parainfluenza eventually grew from bronchioalveolar lavage culture. Antibiotics were started for presumed bacterial superinfection. The patient was finally discharged on hospital day 15 on room air with a final diagnosis of bronchiolitis with superimposed pneumonia.
What is the incidence of serious bacterial infection or superimposed bacterial pneumonia in viral bronchiolitis?
In general, it appears that the risk of bacterial coinfection in infants with bronchiolitis is low. In a large prospective trial assessing the frequency of concurrent serious bacterial infection (SBI) in febrile infants <3 months of age with or without bronchiolitis, only 2.2% of infants with bronchiolitis developed SBI compared with 9.9% of infants without bronchiolitis.8 Thus, in a non–toxic-appearing infant with clinical bronchiolitis, the risk of SBI is lower than that of febrile infants without lower respiratory tract findings. A systematic review of the question concluded that the risk of meningitis, bacteremia, and urinary tract infection was significantly lower than in the general population of febrile infants; however, this review did not tackle the question of secondary bacterial pneumonia.9
Evaluation of superimposed pneumonia in the postpneumococcal conjugate vaccine era was addressed in a prospective study of 165 consecutive children with severe, respiratory syncytial virus bronchiolitis who underwent admission bronchoalveolar lavage sampling. Up to 40% of patients admitted with severe respiratory syncytial virus bronchiolitis were culture positive for potentially pathogenic bacteria in their lower airways.10 Additionally, Kneyber et al11 found that 33% of children with severe disease had positive cultures from endotracheal aspirates. Duttweiler et al12 retrospectively studied 127 infants admitted to the ICU with severe bronchiolitis and found that 44% of ventilated patients had “concomitant bacterial pneumonia” on endotracheal sampling. These studies suggest that infants with more severe disease are at greater risk for superimposed pneumonia, although questions have been raised about the correlation between endotracheal cultures and pneumonia.
The patient was readmitted 3 days after discharge for increased work of breathing and hypoxia. Pulmonary consultants recommended trials of albuterol, ipratropium, hypertonic saline, and budesonide with little change in the patient’s clinical status. The patient was screened for immunodeficiency and the only finding was a low total immunoglobulin A; however, this was interpreted cautiously in the setting of acute illness and follow-up testing was recommended in 6 to 8 weeks. The patient was hospitalized for an additional 7 days without significant change in hypoxia or tachypnea, although he was otherwise well. He was eventually sent home on 0.5 L home oxygen, and a follow-up lung CT scan was planned for at least 2 months after the initial illness. The follow-up CT scan showed persistence of the bilateral ground-glass, interstitial pattern without improvement, and lung biopsy was scheduled. Neuroendocrine cell hyperplasia of infancy (NEHI) was subsequently diagnosed on lung biopsy.
NEHI is a recently described interstitial lung disease of unknown etiology. Clinical presentation includes tachypnea, retractions, hypoxemia, and crackles. On chest radiographs, nonspecific findings often suggest viral lower airway disease. In general, NEHI is a very good bronchiolitis mimic. High-resolution CT yields characteristic radiographic findings of diffuse air trapping and ground-glass densities predominantly in the right middle lobe and lingula.13 Pathohistologic review of lung tissue, the gold standard for diagnosis, reveals hyperplasia of bombesin-immunopositive pulmonary neuroendocrine cells within distal bronchioles and alveolar ducts in the absence of other abnormalities or significant inflammation.
These classic findings were initially explicated in a 2005 report by Deterding et al,14 who described the association of persistent tachypnea of infancy with neuroendocrine cell hyperplasia. Shortly thereafter, a descriptive report of lung biopsy findings in sudden infant death syndrome (SIDS) noted that in SIDS infants, the number of neuroendocrine cells, the size of neuroendocrine cell clusters, and the mean concentration of bombesin-like peptide detected by radioimmunoassay were significantly increased in comparison with those values for age-matched controls.15 At the time, these findings were thought to be suggestive of the underlying pathophysiology in the development of SIDS. Although NEHI is now recognized as a distinct entity, additional studies are needed to determine if there is an increased risk of SIDS in affected children. The available literature suggests that there are no known deaths due to NEHI, but this does not account for its very recent recognition and the rarity of lung biopsy.14
Treatment of NEHI is mainly supportive, namely oxygen supplementation and optimizing nutrition. Failure to thrive is common in infants with this disorder. Trials of corticosteroids have not been shown to eliminate symptoms.14 Limited data suggest that the clinical course is prolonged, but that hypoxemia and tachypnea gradually improve during childhood. Further longitudinal studies are needed before more definitive guidance on prognosis and long-term outcomes can be given.
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- Copyright © 2012 by the American Academy of Pediatrics