viral respiratory infections are a leading cause of illness and hospitalization in infants and children worldwide . in 2009 in the united states , more than 300,000 children were hospitalized as a result of infectious respiratory illness .
children with chronic medical conditions have an increased risk of morbidity and mortality from these viral respiratory infections [ 27 ] . in 2001 , a new virus of the paramyxoviridae family called human metapneumovirus ( hmpv ) was identified .
the virus , a member of the same subfamily as respiratory syncytial virus ( rsv ) , has been credited as the etiology of  non - rsv bronchiolitis  due to its overlapping seasonal distribution [ 911 ] .
children with hmpv typically present with signs and symptoms of upper and lower respiratory tract infection such as fever , cough , tachypnea , and wheezing . in children less than five years of age , rates of hospitalization are similar between hmpv , parainfluenza , and seasonal influenza . nebulized respiratory medications , such as albuterol and racemic epinephrine , have historically been administered in children presenting with viral lower respiratory infection .
recent evidence has led the american academy of pediatrics to recommend against the routine use of inhaled beta - adrenergic agents , such as albuterol , in the treatment of bronchiolitis .
a recent cochrane database systematic review concluded that neither oxygen saturation nor length of hospitalization was improved by use of bronchodilators in bronchiolitis .
another cochrane review concluded that repeated dosing of racemic epinephrine in hospitalized children with bronchiolitis is also not recommended . while there is an abundance of data regarding the frequency of use and efficacy of beta - adrenergic agents and racemic epinephrine in children with rsv
this study employed the following objectives : ( 1 ) to describe the clinical characteristics of patients admitted to the hospital with hmpv infection , ( 2 ) to determine the frequency of albuterol use in this population , and ( 3 ) to compare clinical outcomes , such as hospital length of stay ( los ) , intensive care unit ( icu ) los , supplemental oxygen use , and mechanical ventilation , between hmpv patients who did and did not receive albuterol .
we additionally hypothesized that there would be no relationship between the administration of albuterol and hospital los .
all patients requiring admission to our institution with community - acquired hmpv infection between january and december 2010 were identified .
we defined infection as the detection of hmpv from a nasopharyngeal or endotracheal specimen by polymerase chain reaction ( pcr ) testing obtained within the first 72 hours of admission .
it was the general practice of our institution during the period of study to obtain respiratory viral pcr testing in any patient admitted to the hospital with infectious respiratory symptoms .
the microbiology laboratory at our institution uses a multiplex respiratory viral pcr : the qiagen symphony rgq platform for nucleic acid extraction and amplification and a luminex system and test reagents for the determination of assay results .
other viruses identified with this pcr include rsv , influenza a and influenza b , adenoviruses , parainfluenza viruses 13 , and human rhino / enteroviruses .
we defined viral coinfection as the detection of other viral agents by pcr testing on the same specimen that detected hmpv .
patients with chronic medical conditions associated with increased morbidity and mortality with viral respiratory illness were identified [ 24 , 16 ] .
these conditions included chronic pulmonary conditions , cyanotic heart disease , prematurity , immunocompromised state , neuromuscular disorders , and hemoglobinopathies .
patients with a prior history of wheezing but without a formal diagnosis of asthma were identified from the electronic medical record , including notation of albuterol in home medications and documentation of wheezing in the past medical history or in any other section of clinician charting from that concurrent admission .
review of clinical and administrative databases and the electronic medical record was conducted by a single reviewer to establish hospital los , icu los , use of inhaled respiratory medications ( e.g. , albuterol , levalbuterol , racemic epinephrine , and/or ipratropium ) , supplemental oxygen use , chief complaint , and need for mechanical ventilation .
use of inhaled medications was determined through review of the patient 's medication administration record for the patient 's entire stay .
an  albuterol trial  was defined as receipt of at least one dose of nebulized albuterol during admission and  prolonged albuterol  was defined as continued receipt beyond 24 hours of admission .
these were children documented in the medical chart to clinically improve after albuterol based on a charting provider 's evaluation of the patient .
these providers included physicians , nurse practitioners , and respiratory therapists , and the clinical improvement was charted in varying words , including  improvement in wheezing , decreased respiratory rate , or decreased work of breathing  following a treatment .
based on admitting diagnosis in the electronic medical record , patients were also categorized as admitted with a primary respiratory or nonrespiratory complaint .
supplemental oxygen use was defined as the need for supplemental oxygen not associated with inhaled respiratory treatments .
we calculated that a sample size of 120 patients would be needed to detect a difference in hospital length of stay of one day between groups ( albuterol versus no albuterol ) to achieve 80% power employing previously published hospital los estimates .
all calculations were performed using stata / ic 12.1 ( stata corporation , college station , tx ) .
the median age was 16 months ( interquartile range ( iqr ) 845 months ) and 82 patients were female ( 40% ) .
one hundred eighty - eight patients ( 91% ) had positive specimens obtained prior to , or on the day of , hospital admission .
eighty - three percent of patients presented during the months of december to april with a peak incidence during the month of march ( 61 patients , 29% ) .
the most common diagnoses on admission were acute respiratory tract infection ( 70% ) , status asthmaticus or asthma exacerbation ( 14% ) , vaso - occlusive crisis ( 4% ) , and seizure ( 3% ) .
the characteristics of patients hospitalized with community - acquired laboratory - confirmed hmpv infection are listed in table 1 . of the 31% of patients with a documented previous history of asthma or wheezing ,
one hundred percent of patients admitted with an asthma - related diagnosis received albuterol . of the 179 patients admitted with a nonasthma - related diagnosis , 114 patients ( 64% ) received albuterol .
forty - one patients ( 20% ) were admitted to an icu , either pediatric or cardiac icu . in patients admitted to an icu , the median icu los was four days ( iqr 110 days ) .
one hundred forty - two patients ( 69% ) received a trial of albuterol treatment .
one hundred two patients ( 49% ) received multiple albuterol treatments with albuterol during the first 24 hours of hospitalization .
thirteen patients ( 6% ) required mechanical ventilation and four patients ( 2% ) did not survive to discharge .
we compared patient characteristics and clinical factors between patients who received albuterol and those who did not receive albuterol ( table 2 ) .
there was no difference in hospital los between patients who received albuterol and those who did not .
patients with a previous diagnosis of asthma and those admitted with an asthma - related diagnosis were more likely to receive albuterol ( both p < 0.001 ) .
patients with a nonasthma chronic medical condition were no more likely to receive albuterol than asthmatics and previously healthy patients ( p = 0.09 ) . upon exclusion of asthmatics , those patients with a nonasthma chronic medical condition were more likely to receive albuterol than previously healthy children ( p < 0.001 ) . patients who received albuterol were more likely to have received supplemental oxygen ( p < 0.001 ) .
male patients were more likely to receive albuterol ( p = 0.03 ) than females , although , in our cohort , male patients were more likely to have a history of asthma ( p = 0.01 ) than females .
there was no correlation between age , sex , or chronic medical conditions with length of stay .
patients requiring supplemental oxygen had a longer length of stay ( median 4 days versus 2 days , p < 0.001 ) .
children with prior wheezing or asthma had a shorter los ( p = 0.001 , median 2 days versus 3 days ) .
fifty - five percent of children in this study received prolonged albuterol therapy with a median duration of albuterol administration of four days ( iqr 35 days ) .
patients receiving prolonged albuterol beyond 24 hours had a longer median hospital los ( 3 days versus 2 days , p = 0.025 ) .
this difference ceased to be significant after adjusting for supplemental oxygen use and asthma or prior wheezing .
however , among the 80% of patients that did not require icu admission , prolonged albuterol use was associated with longer hospital los even after adjusting for supplemental oxygen use and asthma or prior wheezing ( p = 0.046 ) .
prolonged albuterol use was associated with an additional 1.7 hospital days after adjusting for supplemental oxygen use and asthma or prior wheezing among the cohort not requiring icu admission .
ninety - eight patients ( 47% ) received at least one other nebulized respiratory medication : ipratropium ( 72 patients ) , racemic epinephrine ( 27 patients ) , dornase alfa ( 2 patients ) , and dexamethasone ( 1 patient ) . patients who received a secondary nebulized respiratory medication
twenty - eight ( 20% ) of the 142 patients who received albuterol were described as albuterol responsive .
as described above , previously healthy children , who comprised 43% of our cohort , were less likely to receive any albuterol than those with asthma or other chronic medical conditions .
forty - five percent of previously healthy children received albuterol trial , with 21% receiving prolonged albuterol .
other viruses recovered included human rhino / enterovirus ( 28 patients ) , adenovirus ( 9 patients ) , rsv ( 2 patients ) , influenza a ( 2 patients ) , and parainfluenza 3 ( 2 patients ) .
there was no association between viral coinfection and any patient characteristics or clinical outcomes , most notably receipt of albuterol or hospital length of stay .

 conclusion # 1 : the frequency of albuterol trial in children hospitalized with hmpv is high ( 69% ) .
the frequency of prolonged albuterol use is high in children with hmpv ( 55% ) .
albuterol was administered to children both with and without a documented past history of wheezing or asthma .
our study observed widespread , frequent , and early ( often within the first 24 hours of hospitalization ) initiation of albuterol therapy to children with hmpv respiratory infection .
this finding presents the question as to the reason for widespread bronchodilator use in this patient population .
this may be true improvement but may also be transient due to concurrent administration of oxygen , other medication adjuncts ( antipyretics , steroids , and antibiotics ) , and/or humidification in the setting of mask administration .
similarly , in a study of bronchodilator effects on airway reactivity in ventilated children with rsv bronchiolitis , only short term benefits were observed . in those children ,
acute improvement in airway reactivity , as evidenced by functional residual capacity , was suggested after albuterol treatments , but a clear translation of this improvement to long term outcomes was not observed . in children with a history of chronic illness and/or wheezing ,
their histories often reveal home use of albuterol or prior presentations with wheezing and albuterol .
this correlates with our observation that 94% of patients with a history of wheezing or asthma received albuterol .
this population , however , does not fully account for the widespread use of albuterol that we observed .
only 31% of patients in the study had a documented wheezing history , while 69% of patients received albuterol . 

conclusion # 2 : the receipt of any albuterol was not associated with length of stay .
we identified no difference in hospital los between hmpv patients who received albuterol treatment and those who did not .
this finding was independent of length of albuterol treatment . in analysis of this conclusion ,
it is useful to consider an illness such as asthma , in which albuterol is a mainstay of treatment .
one study of critically ill asthmatic patients found an association between continuous albuterol and a shorter los as compared to intermittent albuterol administration .
in fact , another study looked at the specific gene known to play a role in response to beta-2 agonists such as albuterol .
this study found asthmatic patients homozygous for glycine at that amino acid to have shorter icu length of stay as compared to other genotypes .
both studies suggest a role for albuterol in improvement of clinical outcomes in asthma ; however , our results would not support a similar expectation in hmpv bronchiolitis .
results of our study are congruent with evidence on which the most recent aap guidelines were based in order to conclude that the routine use of bronchodilators does not have a clear benefit in treatment of bronchiolitis .
our results additionally highlight this finding in bronchiolitis caused specifically by hmpv . with attention to los and
oxygen requirement , our findings do not support the routine use of albuterol in every patient with hmpv . 

conclusion # 3 : prolonged albuterol use , beyond the first 24 hours of hospitalization , is associated with longer hospital length of stay .
as the medical record does not include standardized markers of illness severity , we are unable to definitively rule out illness severity as a confounding variable of this result .
one might propose that chronic illness may parallel illness severity , with those children having a longer los or being more likely to receive continued albuterol
. we did not find an association between chronic medical conditions and length of stay , and a history of wheezing was actually found to be associated with shorter hospitalizations .
a similar study in children with rsv also demonstrated an increased length of stay and duration of oxygen therapy in association with regular albuterol use .
as more is known about hmpv and as pcr results become more rapidly available , knowledge of the pathogen may become useful to clinicians in decisions regarding albuterol continuation beyond 24 hours . limitations of this study are acknowledged as this is a retrospective study where motivations to treat were not consistently clear to the researchers . extensive chart review was conducted in order to capture those patient characteristics ; however , information in electronic records is not fully standardized , nor does it guarantee completeness .
additionally , this study did not determine severity of illness in patients aside from intensive care admission and any potentially complicating chronic illness .
though we found high frequency of albuterol use in this patient population , we do not have a comparison frequency of use in all patients with respiratory illness in our institution .
a patient 's response to albuterol would be the ideal outcome to identify albuterol as the contributing variable , but we are limited to length of stay and prolonged albuterol administration to describe our population clinically .
there is likely a difference between children experiencing an asthma exacerbation versus bronchiolitis secondary to hmpv infection , both in clinical motivators for albuterol and in disease pathophysiology . due to the limitations of the patient chart as well as sample size
, we were unable to analyze these two groups separately in regard to albuterol receipt .
there is limited information on the period of time that hmpv continues to be shed in the nasopharynx of children .
small studies and case reports suggest a period of viral shedding of one to two weeks following acute infection [ 22 , 23 ] .
this prolonged shedding potentially confounds a positive pcr test for hmpv , especially in setting of asymptomatic patients .
our study , however , is predominately symptomatic patients with respiratory symptoms so severe as to require hospital admission . in conclusion ,
the overwhelmingly high frequency of albuterol administration in patients with hmpv infection , despite a lack of recommendations to support its practice in similar lower respiratory illnesses , is a key finding in this study .
we found no clear association between hospital los and albuterol use in our hmpv infected patient population . in the future ,
research involving patients identified to have hmpv infection will be vital and useful in providing a smaller , etiology - specific cohort of patients with clear recommendations for management .
 
 introduction . 
 human metapneumovirus ( hmpv ) is a paramyxovirus from the same subfamily as respiratory syncytial virus ( rsv ) and causes similar acute lower respiratory tract infection . 
 albuterol in the setting of acute rsv infection is controversial and has not yet been studied in hmpv . 
 we sought to determine the frequency of albuterol use in hmpv infection and the association between albuterol administration and patient outcomes . 
 methods . 
 we conducted a retrospective cohort study identifying all patients hospitalized in a tertiary care children 's hospital with laboratory - confirmed hmpv infection between january 2010 and december 2010 . 
 results . 
 there were 207 patients included in the study ; 57% had a chronic medical condition . 
 the median hospital length of stay was 3 days . 
 only 31% of patients in the study had a documented wheezing history , while 69% of patients received at least one albuterol treatment . 
 there was no difference in length of stay between patients who received albuterol and those who did not . 
 conclusion . 
 there is a high frequency of albuterol use in children hospitalized with hmpv infection . as with rsv , 
 evidence may not support routine use of bronchodilators in patients with acute hmpv respiratory infection . 
 research involving additional patient outcomes and illness severity indicators would be useful in future studies . 