Bronchial Casts and Pandemic (H1N1) 2009 Virus Infection

To the Editor: In the late 1990s, triple-reassortant influenza A viruses containing genes from avian, human, and swine influenza viruses emerged and became enzootic in swine herds in North America (1). The first 11 human cases of novel influenza A virus infection were reported to the Centers for Disease Control and Prevention (CDC; Atlanta, GA, USA) from December 2005 through February 2009 (1). In response to those reports, surveillance for human infection with nonsubtypeable influenza A viruses was implemented. 
 
In the spring of 2009, outbreaks of febrile respiratory infections caused by a novel influenza A virus (H1N1) were reported among persons in Mexico, the United States, and Canada (2). Patient specimens were sent to CDC for real-time reverse transcription–PCR (RT-PCR) testing, and from April 15 through May 5, 2009, a total of 642 infections with the virus, now called pandemic (H1N1) 2009 virus, were confirmed. Of those 642 patients, 60% were <18 years of age, indicating that children may be particularly susceptible to pandemic (H1N1) 2009 (2). 
 
Children and adults with preexisting underlying respiratory conditions, such as asthma, are at increased risk for complications from infection with pandemic (H1N1) 2009 virus. One possible complication is plastic bronchitis, a rare respiratory illness characterized by formation of large gelatinous or rigid branching airway casts (3). Plastic bronchitis is a potentially fatal condition induced by bronchial obstruction from mucus accumulation resulting from infection, inflammation, or vascular stasis (4). We report a case of bronchial casts that caused atelectasis of the right lung of a child infected with influenza A pandemic (H1N1) 2009 virus. 
 
A 6-year-old boy with asthma and a 1-day history of fever and cough was referred to a hospital pediatrics department because of dyspnea. Clinical examination at hospital admission found respiratory distress, as shown by tachypnea (respiratory rate 66 breaths/min) and inspiratory retraction, deficient vesicular sounds over the right lung field, elevated blood levels of immunoglobulin E (1,770 IU/mL) and a reduced number of lymphocytes (483 cells/μL), and radiographic evidence of atelectasis of the right lung and hyperinflation of the left lung without air leakage (Figure, panel A). Pandemic (H1N1) 2009 virus infection was confirmed by real-time RT-PCR, as described (5), of an endotracheal aspirate. Real-time PCR ruled out Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Legionella pneumophila, Chlamydophila pneumoniae, S. pyogenes, respiratory syncytial viruses A and B, seasonal influenza viruses A and B, parainfluenza viruses 1–3, rhinovirus, enterovirus, human metapneumovirus, human bocavirus, and adenovirus (6). While the patient was breathing room air, his percutaneously monitored oxygen saturation was 86%; respiratory support by mechanical ventilation was then initiated. Mucus casts were extracted by intratracheal suction (Figure, panel B). The patient was treated with an inhaled bronchodilator, intravenous methylprednisolone (20–60 mg/day for 7 days), and antiviral (oseltamivir) and antimicrobial (ampicillin/sulbactam) drugs. 
 
 
 
Figure 
 
A) Chest radiograph obtained at hospital admission from a child infected with influenza subtype H1N1 virus. The image shows atelectasis of the right lung and hyperinflation of the left lung; arrows indicate obstruction of the right main bronchus. B) Macroscopic ... 
 
 
 
On hospital day 2, chest radiographs showed that atelectasis of the right lower lobe had partially resolved (Figure, panel C). A histologic examination of casts (May-Giemsa stain; Figure, ​,panelpanel D) indicated a mucoid substance containing a predominantly eosinophilic infiltrate (>90% of cells). The patient’s respiratory condition during 11 days of oxygen supplementation gradually improved, and he was discharged on hospital day 18. 
 
Plastic bronchitis is related mainly to respiratory, cyanotic cardiac (post-Fontan), and hematologic (sickle cell anemia) diseases. A diagnosis of plastic bronchitis is determined on the basis of clinical findings (pointing to allergic and asthmatic, cardiac, or idiopathic etiologies) and pathologic findings (inflammatory vs. noninflammatory) on examination of casts (3). Inflammatory casts contain fibrin, eosinophils, and Charcot-Leyden crystals; noninflammatory casts contain mucin and exhibit vascular hydrostatic changes. The case presented here was the allergic-inflammatory type of plastic bronchitis. 
 
Various treatments for plastic bronchitis have been described and vary from cast removal by expectoration or by bronchoscopy (7,8). Other interventions involve cast disruption by tissue plasminogen activator or urokinase and prevention of cast formation by use of mucolytic agents, steroids, or anticoagulants. However, evidence remains anecdotal because too few plastic bronchitis patients are available for clinical trials. Details of steroid dosage will need to be clarified for pandemic (H1N1) 2009 virus–infected children with respiratory distress from bronchitis and pneumonia. 
 
In Iran during 1998–2001, avian influenza (H9N2) infection among broiler chickens resulted in 20%–60% mortality rates on affected farms (9). Macroscopic examination of specimens from infected chickens showed extensive hyperemia of the respiratory tract, followed by exudate and casts extending from the tracheal bifurcation to the secondary bronchi. Light microscopy indicated severe necrotizing tracheitis. Pandemic (H1N1) 2009 can produce similar airway cast formation in humans; severe respiratory distress reflects extensive obstruction of the respiratory system. 
 
Healthcare providers should be aware of the possibility of bronchial casts when examining children with influenza (H1N1) infection accompanied by atelectasis. Steroids can be administered early in infection to avoid cast formation, and antiviral drug therapy and respiratory support can be used for influenza (H1N1)–infected children in whom airway casts have developed.

cifi c. The high plasma creatinine level in the newborn sometimes refl ects the mother's plasma creatinine level (9). However, kidney function of the mother of the newborn was within normal limits at the time of Caesarean section; plasma creatinine level of 0.7 mg/dL. An elevated plasma creatinine level is observed frequently in premature infants due to immaturity of the kidney tissue and will usually decrease within a few weeks. Oseltamivir was administered with dose adjustment based on the infant's estimated glomerular fi ltration rate. The recommended dose of oseltamivir for glomerular fi ltration rate <30 mL/ min/1.73 m 2 is 2-3 mg/kg/day, based on preliminary data obtained by a National Institutes of Health-funded Collaborative Antiviral Study Group (10). The success of our management strategy for this case suggests early treatment with oseltamivir can prevent severe illness in newborns with perinatal infl uenza A pandemic (H1N1) 2009 infection. Children and adults with preexisting underlying respiratory conditions, such as asthma, are at increased risk for complications from infection with pandemic (H1N1) 2009 virus. One possible complication is plastic bronchitis, a rare respiratory illness characterized by formation of large gelatinous or rigid branching airway casts (3). Plastic bronchitis is a potentially fatal condition induced by bronchial obstruction from mucus accumulation resulting from infection, infl ammation, or vascular stasis (4). We report a case of bronchial casts that caused atelectasis of the right lung of a child infected with infl uenza A pandemic (H1N1) 2009 virus.

References
A 6-year-old boy with asthma and a 1-day history of fever and cough was referred to a hospital pediatrics department because of dyspnea. Clinical examination at hospital admission found respiratory distress, as shown by tachypnea (respiratory rate 66 breaths/ min) and inspiratory retraction, deficient vesicular sounds over the right lung fi eld, elevated blood levels of immunoglobulin E (1,770 IU/mL) and a reduced number of lymphocytes (483 cells/μL), and radiographic evidence of atelectasis of the right lung and hyperinfl ation of the left lung without air leakage ( Figure, panel A). Pandemic (H1N1) 2009 virus infection was confi rmed by real-time RT-PCR, as described (5) (6). While the patient was breathing room air, his percutaneously monitored oxygen saturation was 86%; respiratory support by mechanical ventilation was then initiated. Mucus casts were extracted by intratracheal suction (Figure, panel B). The patient was treated with an inhaled bronchodilator, intravenous methylprednisolone (20-60 mg/day for 7 days), and antiviral (oseltamivir) and antimicrobial (ampicillin/sulbactam) drugs.
On hospital day 2, chest radiographs showed that atelectasis of the right lower lobe had partially resolved (Figure, panel C). A histologic examination of casts (May-Giemsa stain; Figure, panel D) indicated a mucoid substance containing a predominantly eosinophilic infi ltrate (>90% of cells). The patient's respiratory condition during 11 days of oxygen supplementation gradually improved, and he was discharged on hospital day 18.
Plastic bronchitis is related mainly to respiratory, cyanotic cardiac (post-Fontan), and hematologic (sickle cell anemia) diseases. A diagnosis of plastic bronchitis is determined on the basis of clinical fi ndings (pointing to allergic and asthmatic, cardiac, or idiopathic etiologies) and pathologic fi ndings (infl ammatory vs. noninfl ammatory) on examination of casts (3). Infl ammatory casts contain fi brin, eosinophils, and Charcot-Leyden crystals; noninfl ammatory casts contain mucin and exhibit vascular hydrostatic changes. The case presented here was the allergic-infl ammatory type of plastic bronchitis.
Various treatments for plastic bronchitis have been described and vary from cast removal by expectoration or by bronchoscopy (7,8). Other interventions involve cast disruption by tissue plasminogen activator or urokinase and prevention of cast formation by use of mucolytic agents, steroids, or anticoagulants. However, evidence remains anecdotal because too few plastic bronchitis patients are available for clinical trials. Details of steroid dosage will need to be clarifi ed for pandemic (H1N1) 2009 virus-infected children with respiratory distress from bronchitis and pneumonia.
In Iran during 1998-2001, avian infl uenza (H9N2) infection among broiler chickens resulted in 20%-60% mortality rates on affected farms (9). Macroscopic examination of specimens from infected chickens showed extensive hyperemia of the respiratory tract, followed by exudate and casts extending from the tracheal bifurcation to the secondary bronchi. Light microscopy indicated severe necrotizing tracheitis. Pandemic (H1N1) 2009 can produce similar airway cast formation in humans; severe respiratory distress refl ects extensive obstruction of the respiratory system.
Healthcare providers should be aware of the possibility of bronchial casts when examining children with infl uenza (H1N1) infection accompanied by atelectasis. Steroids can be administered early in infection to avoid cast formation, and antiviral drug therapy and respiratory support can be used for infl uenza (H1N1)-infected children in whom airway casts have developed.