The similarities and differences of epidemic cycles of chronic obstructive pulmonary disease and asthma exacerbations

The majority of chronic obstructive pulmonary disease (COPD) and asthma exacerbations in both children and adults are associated with respiratory viral infections and are cyclic in nature. Some variation in these cycles is associated with the timing of the appearance of respiratory viruses, particularly influenza and respiratory syncytial virus. Much more, however, is associated with signal events that are of either fixed or predictable timing. In children, asthma exacerbations reach epidemic levels following school return after the summer vacation and these are predominantly associated with rhinovirus infections. Although younger adults experience a rise in asthma exacerbations at this time, these are secondary to the epidemic in children. Older adults with either COPD or asthma experience only a slightly elevated risk of exacerbations after school return, and hospital presentations for pneumonia in any age group show only marginal increases at that time. Exacerbations of both COPD and adult asthma, with increasing risk with age, are at their highest average annual levels during the Christmas period. This effect appears to be independent of the timing of above average levels of influenza, RSV, parainfluenza, or adenovirus detections; however, hospitalization for respiratory tract infections in all age groups reaches high levels at the same time. Both the post-summer vacation asthma epidemic and the Christmas epidemic of COPD, asthma, and pneumonia are synchronous with the timing of signal events, the day of school return for the former and Christmas Day for the latter, and have been for several years. The agents responsible for the Christmas epidemic of respiratory diseases have not yet been identified. The differences between age and disease exacerbation patterns after school return and at Christmas suggest that either different agents are involved or that the response to a common agent is different between the two signal events.     

Population Decline in COPD Admissions During the COVID-19 Pandemic Associated with Lower Burden of Community Respiratory Viral Infections

BackgroundThe Coronavirus disease 2019 (COVID-19) pandemic has led to widespread implementation of public health measures, such as stay-at-home orders, social distancing, and masking mandates. In addition to decreasing spread of severe acute respiratory syndrome coronavirus 2, these measures also impact the transmission of seasonal viral pathogens, which are common triggers of chronic obstructive pulmonary disease (COPD) exacerbations. Whether reduced viral prevalence mediates reduction in COPD exacerbation rates is unknown.MethodsWe performed retrospective analysis of data from a large, multicenter health care system to assess admission trends associated with community viral prevalence and with initiation of COVID-19 pandemic control measures. We applied difference-in-differences analysis to compare season-matched weekly frequency of hospital admissions for COPD prior to and after implementation of public health measures for COVID-19. Community viral prevalence was estimated using regional Centers for Disease Control and Prevention test positivity data and correlated to COPD admissions.ResultsData involving 4422 COPD admissions demonstrated a season-matched 53% decline in COPD admissions during the COVID-19 pandemic, which correlated to community viral burden (r = 0.73; 95% confidence interval, 0.67-0.78) and represented a 36% greater decline over admission frequencies observed in other medical conditions less affected by respiratory viral infections (incidence rate ratio 0.64; 95% confidence interval, 0.57-0.71, P < .001). The post-COVID-19 decline in COPD admissions was most pronounced in patients with fewer comorbidities and without recurrent admissions.ConclusionThe implementation of public health measures during the COVID-19 pandemic was associated with decreased COPD admissions. These changes are plausibly explained by reduced prevalence of seasonal respiratory viruses.     

Air pollution and hospital admissions for respiratory conditions in Rome, Italy.

Most of the evidence regarding the association between particulate air pollution and emergency room visits or hospital admissions for respiratory conditions and asthma comes from the USA. European time-series analyses have suggested that gaseous air pollutants are important determinants of acute hospitalization for respiratory conditions, at least as important as particulate mass. The association between daily mean levels of suspended particles and gaseous pollutants (sulphur dioxide, nitrogen dioxide, carbon monoxide, ozone) was examined. The daily emergency hospital admissions for respiratory conditions in the metropolitan area of Rome during 1995-1997 were also recorded. Daily counts of hospital admissions for total respiratory conditions (43 admissions day(-1)), acute respiratory infections including pneumonia (18 day(-1)), chronic obstructive pulmonary disease (COPD) (13 day(-1)), and asthma (4.5 day(-1)) among residents of all ages and among children (0-14 yrs) were analysed. The generalized additive models included spline smooth functions of the day of study, mean temperature, mean humidity, influenza epidemics, and indicator variables for day of the week and holidays. Total respiratory admissions were significantly associated with same-day level of NO2 (2.5% increase per interquartile range (IQR) change, 22.3 microg x m(-3)) and CO (2.8% increase per IQR, 1.5 mg x m(-3)). No effect was found for particulate matter and SO2, whereas O3 was associated with admissions only among children (lag 1, 5.5% increase per IQR, 23.9 microg x m3). The effect of NO2 was stronger on acute respiratory infections (lag 0, 4.0% increase) and on asthma among children (lag 1, 10.7% increase). The admissions for all ages for asthma and COPD were associated only with same-day level of CO (5.5% and 4.3% increase, respectively). Multipollutant models confirmed the role of CO on all respiratory admissions, including asthma and COPD, and that of NO2 on acute respiratory infections. Among children, O3 remained a strong indicator of acute respiratory infections. Carbon monoxide and photochemical pollutants (nitrogen dioxide, ozone) appear to be determinants of acute respiratory conditions in Rome. Since carbon monoxide and nitrogen dioxide are good indicators of combustion products from traffic related sources, the detected effect may be due to unmeasured fine and ultrafine particles.     

Role of viruses in exacerbations of chronic obstructive pulmonary disease

Exacerbations of chronic obstructive pulmonary disease (COPD) are a major cause of morbidity and mortality and hospital admission. Respiratory viral infections, especially rhinoviruses, are a major cause of COPD exacerbations, with upper respiratory tract infections being associated with over 50% of COPD exacerbations. The presence of an upper respiratory tract infection leads to a more severe exacerbation and a longer symptom recovery time at exacerbation. Respiratory viral infections occurring during COPD exacerbations are more likely to lead to hospitalization. Sputum inflammatory markers were found to be higher in those patients with symptoms of a common cold or where rhinovirus was detected at exacerbation, thus suggesting that viral infections lead to greater airway inflammation and thus more severe exacerbations. COPD exacerbations are associated also with systemic inflammatory effects with increases in markers such as plasma fibrinogen and interleukin-6. Respiratory viruses have also been detected when the patients are stable, and this suggests that chronic viral infection may occur. Strategies to prevent viral infection will have a significant effect on the morbidity of COPD and will improve quality of life.     

A community-based, time-matched, case-control study of respiratory viruses and exacerbations of COPD

Respiratory viruses are associated with severe acute exacerbations of chronic obstructive pulmonary disease (COPD) in hospitalized patients. However, exacerbations are increasingly managed in the community, where the role of viruses is unclear. In community exacerbations, the causal association between viruses and exacerbation maybe confounded by random fluctuations in the prevalence of circulating respiratory viruses. Therefore, to determine whether viral respiratory tract infections are causally associated with community exacerbations, a time-matched case-control study was performed. Ninety-two subjects (mean age 72 yrs), with moderate to severe COPD, (mean FEV(1) 40% predicted), were enrolled. Nasopharyngeal swabs for viral multiplex polymerase chain reaction and atypical pneumonia serology were obtained at exacerbation onset. Control samples were collected in synchrony, from a randomly selected stable patient drawn from the same cohort. In 99 weeks of surveillance, there were 148 exacerbations. Odds of viral isolation were 11 times higher in cases, than their time-matched controls (34 discordant case-control pairs; in 31 pairs only the case had virus and in three pairs only control). Picornavirus (26), influenza A (3), parainfluenza 1,2,3 (2), respiratory syncytial virus (1), and adenovirus (1) were detected in cases while adenovirus (1) and picornavirus (2) were detected in controls. In patients with moderate or severe COPD the presence of a virus in upper airway secretions is strongly associated with the development of COPD exacerbations. These data support the causative role of viruses in triggering COPD exacerbations in the community.     

Epidemiology of acute viral respiratory tract infections in Korean children

OBJECTIVE: Viruses are the most common causes of respiratory tract infection in children. We investigated the aetiologies and the epidemiological features of acute viral respiratory tract infections in Korean children. METHODS: We tried to isolate respiratory syncytial virus (RSV) and parainfluenza virus from January 1994, influenza virus from February 1995, and adenovirus from April 1996 through August 1998, and identified the isolated viruses by indirect immunofluorescence (IF) staining in the children hospitalized with acute respiratory tract infections (ARTI). RESULTS: Virus was identified in 360 of 1389 (25.9%) nasopharyngeal aspirates cultured. Of a total of 392 viruses, 164 (41.8%) RSV, 90 (23%) parainfluenza virus, 66 (16.8%) influenza A virus, 54 (13.8%) adenovirus, and 18 (4.6%) influenza B virus were cultured, including cases in mixed viral infections. The male to female ratio of the culture-positive patients was 2:1, and the proportions of the patients aged >6 months, 6-11 months, 1, 2, 3, 4, 5, 6-7, 8-9, and >10 years were 22.5, 29.5, 25.7, 9.5, 3.8, 3.8, 1.7, 1.7, 1.2, and 0.6%, respectively. The major clinical diagnosis was bronchiolitis for RSV, croup for parainfluenza virus, and pneumonia for adenovirus and influenza virus. Infections by RSV, parainfluenza virus, and influenza virus occurred in annual epidemics, and infections by adenovirus occurred annually with or without epidemics. There were somewhat larger epidemics by adenovirus and influenza virus in May to July 1996 and March to June 1997, respectively. CONCLUSIONS: Viral agents are one of the main aetiologies and the main causes of admission in Korean children with ARTI.     

The Christmas season as a risk factor for chronic obstructive pulmonary disease exacerbations

BACKGROUND

Epidemics of hospitalization for chronic obstructive pulmonary disease (COPD) occur annually during the Christmas holidays, and COPD exacerbations commonly coincide with respiratory viral infections.

OBJECTIVE

To compare the incidence and determinants of COPD exacerbations occurring between the Christmas holiday period and the remainder of the winter season.

METHODS

Seventy-one subjects with COPD of mixed severity faxed daily symptom diaries to a computer monitoring system from December 1, 2006, to April 30, 2007. Possible exacerbations prompted a home visit for assessment, spirometry and specimen collection for virological testing.

RESULTS

Study subjects submitted a total of 95.4% of possible daily symptom diary sheets by fax. Of 114 possible COPD exacerbations detected using the faxed diaries, 110 met the Anthonisen criteria for true exacerbations. A total of 47 exacerbations (mean 6.7/week) occurred during the Christmas holiday period, while 63 exacerbations (mean 4.3/week) occurred during the remainder of winter. Of the Christmas period exacerbations and of those in the balance of winter, 21 (44%) and 20 (32%), respectively, coincided with respiratory viral infections.

CONCLUSIONS

The incidence of COPD exacerbations during the Christmas period was greater than during the rest of winter in 2006/2007 and peaked immediately before Christmas – in contrast to hospital presentation for COPD, which peaked during the Christmas week. No clear role of respiratory viral infections in the increased rate of exacerbations during the Christmas period was established in the present study. COPD patients were highly compliant with daily symptom reporting using faxed daily diaries, which permitted nearly complete detection of all exacerbations that occurred at incidence.     

Infections and airway inflammation in chronic obstructive pulmonary disease severe exacerbations

RATIONALE: Severe exacerbations of chronic obstructive pulmonary disease (COPD) are major causes of health care costs mostly related to hospitalization. The role of infections in COPD exacerbations is controversial. OBJECTIVES: We investigated whether COPD exacerbations requiring hospitalization are associated with viral and/or bacterial infection and evaluated relationships among infection, exacerbation severity, assessed by reduction of FEV1, and specific patterns of airway inflammation. METHODS: We examined 64 patients with COPD when hospitalized for exacerbations, and when in stable convalescence. We measured lung function, blood gases, and exhaled nitric oxide, and examined sputum for inflammation and for viral and bacterial infection. RESULTS: Exacerbations were associated with impaired lung function (p < 0.01) and increased sputum neutrophilia (p < 0.001). Viral and/or bacterial infection was detected in 78% of exacerbations: viruses in 48.4% (6.2% when stable, p < 0.001) and bacteria in 54.7% (37.5% when stable, p = 0.08). Patients with infectious exacerbations (29.7% bacterial, 23.4% viral, 25% viral/bacterial coinfection) had longer hospitalizations (p < 0.02) and greater impairment of several measures of lung function (all p < 0.05) than those with noninfectious exacerbations. Patients with exacerbations with coinfection had more marked lung function impairment (p < 0.02) and longer hospitalizations (p = 0.001). Sputum neutrophils were increased in all exacerbations (p < 0.001) and were related to their severity (p < 0.001), independently of the association with viral or bacterial infections; sputum eosinophils were increased during (p < 0.001) virus-associated exacerbations. CONCLUSIONS: Respiratory infections are associated with the majority of COPD exacerbations and their severity, especially those with viral/bacterial coinfection. Airway neutrophilia is related to exacerbation severity regardless of viral and/or bacterial infections. Eosinophilia is a good predictor of viral exacerbations.     

Respiratory viruses, symptoms, and inflammatory markers in acute exacerbations and stable chronic obstructive pulmonary disease.

The effects of respiratory viral infection on the time course of chronic obstructive pulmonary disease (COPD) exacerbation were examined by monitoring changes in systemic inflammatory markers in stable COPD and at exacerbation. Eighty-three patients with COPD (mean [SD] age, 66.6 [7.1] yr, FEV(1), 1.06 [0.61] L) recorded daily peak expiratory flow rate and any increases in respiratory symptoms. Nasal samples and blood were taken for respiratory virus detection by culture, polymerase chain reaction, and serology, and plasma fibrinogen and serum interleukin-6 (IL-6) were determined at stable baseline and exacerbation. Sixty-four percent of exacerbations were associated with a cold occurring up to 18 d before exacerbation. Seventy-seven viruses (39 [58.2%] rhinoviruses) were detected in 66 (39.2%) of 168 COPD exacerbations in 53 (64%) patients. Viral exacerbations were associated with frequent exacerbators, colds with increased dyspnea, a higher total symptom count at presentation, a longer median symptom recovery period of 13 d, and a tendency toward higher plasma fibrinogen and serum IL-6 levels. Non-respiratory syncytial virus (RSV) respiratory viruses were detected in 11 (16%), and RSV in 16 (23.5%), of 68 stable COPD patients, with RSV detection associated with higher inflammatory marker levels. Respiratory virus infections are associated with more severe and frequent exacerbations, and may cause chronic infection in COPD. Prevention and early treatment of viral infections may lead to a decreased exacerbation frequency and morbidity associated with COPD.     

Effects of COVID-19 and Social Distancing on Rhinovirus Infections and Asthma Exacerbations

Since their discovery in the 1950s, rhinoviruses (RVs) have been recognized as a major causative agent of the “common cold” and cold-like illnesses, accounting for more than 50% of upper respiratory tract infections. However, more than that, respiratory viral infections are responsible for approximately 50% of asthma exacerbations in adults and 80% in children. In addition to causing exacerbations of asthma, COPD and other chronic lung diseases, RVs have also been implicated in the pathogenesis of lower respiratory tract infections including bronchiolitis and community acquired pneumonia. Finally, early life respiratory viral infections with RV have been associated with asthma development in children. Due to the vast genetic diversity of RVs (approximately 160 known serotypes), recurrent infection is common. RV infections are generally acquired in the community with transmission occurring via inhalation of aerosols, respiratory droplets or fomites. Following the outbreak of coronavirus disease 2019 (COVID-19), exposure to RV and other respiratory viruses was significantly reduced due to social-distancing, restrictions on social gatherings, and increased hygiene protocols. In the present review, we summarize the impact of COVID-19 preventative measures on the incidence of RV infection and its sequelae.     

Association of viral and Mycoplasma pneumoniae infections with acute respiratory illness in patients with chronic obstructive pulmonary diseases

The relative importance of respiratory virus and M. pneumoniae infections as causes of acute respiratory illnesses was studied over an 8 yr period in 150 subjects who were normal or who had varying degrees of chronic obstructive pulmonary disease (COPD). Viral or M. pneumoniae infections were associated with 186 of 1,030 (18%) illnesses studied, whereas these infections were detected in only 86 of 1,398 (6%) illness-free periods (P less than 0.01). Rhinoviruses, influenza viruses, parainfluenza viruses and coronaviruses were each significantly associated with acute respiratory illnesses. The occurrence of acute respiratory illnesses and viral infections was the same in subjects with moderate to severe COPD as it was in subjects who were normal or who had mild disease.     

Occasional review: Influenza in COPD: pathogenesis, prevention, and treatment

Influenza viruses cause respiratory tract infections that in patients with underlying lung diseases such as chronic obstructive pulmonary disease (COPD) are associated with exacerbations and excess morbidity and mortality. Typically, influenza B is associated with relatively mild, local outbreaks, whereas influenza A is the cause of world-wide pandemics. Upon infection, two antigens present on the viral surface, hemagglutinin and neuraminidase result in human immunity, but since many subtypes of these antigens exist that vary over time, immunity in the population is blunted. Vaccination is advocated in high-risk groups including patients with underlying (lung) diseases and in the elderly, and needs to be repeated annually with vaccines expected to cover the expected change in viral antigenicity. When started early, antiviral drugs, especially neuraminidase-inhibitors can be prescribed in adjunct to nonspecific interventions in an attempt to shorten disease duration and to prevent complications in case of an influenza infection. Currently, the effectiveness of antiviral drugs specifically in patients with COPD has not been proven.     

Viruses associated with acute lower respiratory tract infections in children from the eastern highlands of Papua New Guinea (1983-1985)

This study, conducted at Goroka Hospital from January 1983 to June 1985, examined the viruses identified in nasopharyngeal aspirates (NPA) and urines collected from 716 hospitalised children with moderate or severe pneumonia, in NPA from 170 children with mild pneumonia treated as outpatients and in NPA from a control group of 428 children attending the outpatient department of Goroka Hospital suffering from minor ailments other than upper or lower respiratory tract infections. One or more viruses were identified from 68%, 51% and 43% of children with moderate or severe pneumonia, mild pneumonia and the control group, respectively. One-third of viruses were identified in conjunction with another virus in both control and sick children. Viral identification rates were highest in children under 1 year of age. Cytomegalovirus, adenoviruses, respiratory syncytial virus (RSV), measles and rhinoviruses were the most frequently identified viruses. RSV was associated with mild as well as moderate and severe disease. No virus was associated with an increased risk of death. Annual epidemics of RSV occurred during the wet season. An epidemic of influenza A virus and also influenza B virus and 3 epidemics of parainfluenza 3 virus occurred during the study period. The high viral identification rates in this study suggest a high frequency of transmission associated with the social structure and environment of Papua New Guinean highland villages and high population mobility.     

Viral etiology of acute exacerbations of COPD in Hong Kong

INTRODUCTION: Viral respiratory infections may precipitate acute exacerbations of COPD (AECOPD). However, little is known about viral etiology related to AECOPD in Asia. We aimed to study the viral etiology of AECOPD in Hong Kong. METHODS: Patients admitted to an acute hospital in Hong Kong with AECOPD were recruited prospectively from May 1, 2004, to April 30, 2005. Nasopharyngeal aspirate was collected and assessed by polymerase chain reaction (PCR) and viral culture. Spirometry was performed in the stable phase at 2 to 3 months after hospital discharge. RESULTS: There were 262 episodes of AECOPD among 196 patients (mean age, 75.7 +/- 7.7 years [+/- SD]; 160 men). Mean FEV(1) was 39.6 +/- 18.9% of predicted normal, and FEV(1)/FVC ratio was 58.0 +/- 15.2%. Fifty-eight episodes (22.1%) yielded positive viral PCR results. The viruses identified were influenza A (7.3%), coronavirus OC43 (4.6%), rhinovirus (3.1%), influenza B (2.7%), and respiratory syncytial virus (2.3%). The diagnostic yield of viral identification by PCR was 2.7 times higher than that based on conventional viral culture. The rates of identifying a positive viral etiology by PCR were similar among the subjects with FEV(1) >or= 50%, >or= 30 to 50%, and < 30% of predicted normal. Viral infection appeared to have no effect on subsequent readmissions or mortality rate over a study period of 1 year CONCLUSION: Influenza A and two less-attended viruses, coronavirus OC43 and rhinovirus, were the common etiologic agents in patients hospitalized with AECOPD in Hong Kong. These should be considered in developing diagnostic and intervening strategies pertaining to AECOPD.     

Influenza vaccination in patients with asthma: effect on the frequency of upper respiratory tract infections and exacerbations.

Influenza epidemics of variable extent and severity occur every winter and are frequently associated with exacerbations of asthma. Accordingly, annual vaccination against influenza is recommended for patients with asthma. However, there are very limited data concerning its protective effect in this group of patients. The aim of this study was to assess the effect of influenza vaccination on the frequency of upper respiratory tract infections and also asthma-related outcomes such as exacerbation rates, hospital admissions, and rescue courses of oral corticosteroids in patients with stable asthma. Between September 15 and November 7, 2001, a total of 128 patients with asthma were randomly assigned to receive (n = 86) and not to receive vaccine (n = 42). The primary outcome measures were frequency of upper respiratory tract infections and exacerbations of asthma during the winter following vaccination. Study subjects were asked to record the presence and duration of symptoms suggestive of an upper respiratory tract infection and call their physician in the presence of conditions suggestive of an exacerbation until March 2002. Among the vaccinated group, 48% of the patients reported that they had no upper respiratory tract infection during the winter following injection, whereas 57% of nonvaccinated participants were upper respiratory symptom free during the same period (p > 0.05). The frequency of upper respiratory tract infection was also not different between the two groups in all severity forms of asthma (p > 0.05). There was no significant difference in the frequency of exacerbations of asthma between the two groups during the study period (p > 0.05). None of the vaccinated group was hospitalized due to an asthma attack; however, two patients (4.8%) in the nonvaccinated group had to be hospitalized following an exacerbation (p > 0.05). In summary, our findings do not support the protective effect of influenza vaccination for patients with asthma. However, no firm conclusions on this effect of the vaccine can be made without the data on the rate of influenza epidemic in that season and without the knowledge of the cause of upper respiratory tract infections in those patients. Therefore, we believe randomized, double-blind, placebo-controlled studies, including larger subgroups of severe asthmatics, are needed to evaluate the protective effect of influenza vaccination in asthma.     

Masking for COVID-19 Is Associated with Decreased Emergency Department Utilization for Non-COVID Viral Illnesses and Respiratory Conditions in Maryland

BackgroundMasking, which is known to decrease the transmission of respiratory viruses, was not widely practiced in the United States until the coronavirus disease 2019 (COVID-19) pandemic. This provides a natural experiment to determine whether the percentage of community masking was associated with decreases in emergency department (ED) visits due to non-COVID viral illnesses (NCVIs) and related respiratory conditions.MethodsIn this observational study of ED encounters in a 11-hospital system in Maryland during 2019-2020, year-on-year ratios for all complaints were calculated to account for “lockdowns” and the global drop in ED visits due to the pandemic. Encounters for specific complaints were identified using the International Classification of Diseases, version 10. Encounters with a positive COVID test were excluded. Linear regression was used to determine the association of publicly available masking data with ED visits for NCVI and exacerbations of asthma and chronic obstructive pulmonary disease (COPD), after adjusting for patient age, sex, and medical history.ResultsThere were 285,967 and 252,598 ED visits across the hospital system in 2019 and 2020, respectively. There was a trend toward an association between the year-on-year ratio for all ED visits and the Maryland stay-at-home order (parameter estimate = -0.0804, P = .10). A 10% percent increase in the prevalence of community masking was associated with a 17.0%, 8.8%, and 9.4% decrease in ED visits for NCVI and exacerbations of asthma exacerbations and chronic obstructive pulmonary disease, respectively (P < .001 for all).ConclusionsIncreasing the prevalence of masking is associated with a decrease in ED visits for viral illnesses and exacerbations of asthma and COPD. These findings may be valuable for future public health responses, particularly in future pandemics with respiratory transmission or in severe influenza seasons.     

Record linkage study of the pathogen‐specific burden of respiratory viruses in children

Background

Reliance on hospital discharge diagnosis codes alone will likely underestimate the burden of respiratory viruses.

Objectives

To describe the epidemiology of respiratory viruses more accurately, we used record linkage to examine data relating to all children hospitalized in Western Australia between 2000 and 2012.

Patients/Methods

We extracted hospital, infectious disease notification and laboratory data of a cohort of children born in Western Australia between 1996 and 2012. Laboratory records of respiratory specimens collected within 48 hours of admission were linked to hospitalization records. We calculated the frequency and rates of virus detection. To identify groups where under‐ascertainment for respiratory viruses was greatest, we used logistic regression to determine factors associated with failure to test.

Results and conclusions

Nine percentage of 484 992 admissions linked to a laboratory record for respiratory virus testing. While 62% (n = 26 893) of laboratory‐confirmed admissions received respiratory infection diagnosis codes, 38% (n = 16 734) had other diagnoses, notably viral infection of unspecified sites. Of those tested, incidence rates were highest for respiratory syncytial virus (247 per 100 000 child‐years) followed by parainfluenza (63 per 100 000 child‐years). Admissions among older children and those without a respiratory diagnosis were associated with failure to test for respiratory viruses. Linked data can significantly enhance diagnostic codes when estimating the true burden of disease. In contrast to current emphasis on influenza, respiratory syncytial virus and parainfluenza were the most common viral pathogens among hospitalized children. By characterizing those failing to be tested, we can begin to quantify the under‐ascertainment of respiratory viruses.     

Multiple versus single virus respiratory infections: viral load and clinical disease severity in hospitalized children

Please cite this paper as: Martin et al. (2012) Multiple versus single virus respiratory infections: viral load and clinical disease severity in hospitalized children. Influenza and Other Respiratory Viruses 6(1), 71–77. Background Molecular testing for viral pathogens has resulted in increasing detection of multiple viruses in respiratory secretions of ill children. The clinical impact of multiple virus infections on clinical presentation and outcome is unclear. Objectives To compare clinical characteristics and viral load between children with multiple virus versus single virus illnesses. Patients/methods Eight hundred and ninety‐three residual nasal wash samples from children treated for respiratory illness at Children’s Hospital, Seattle, from September 2003 to September 2004 were evaluated by quantitative PCR for respiratory syncytial virus (RSV), human metapneumovirus (hMPV), influenza (Flu), parainfluenza, adenoviruses, and coronaviruses (CoV). Illness severity and patient characteristics were abstracted from medical charts. Results Coinfections were identified in 103 (18%) of 566 virus‐positive samples. Adenovirus was most commonly detected in coinfections (52%), followed by CoV (50%). Illnesses with a single virus had increased risk of oxygen requirement (P = 0·02), extended hospital stays (P = 0·002), and admissions to the inpatient (P = 0·02) or intensive care units (P = 0·04). For Adv and PIV‐1, multiple virus illnesses had a significantly lower viral load (log₁₀ copies/ml) than single virus illnesses (4·2 versus 5·6, P = 0·007 and 4·2 versus 6·9, P < 0·001, respectively). RSV, Flu‐A, PIV‐3, and hMPV viral loads were consistently high whether or not another virus was detected. Conclusions Illnesses with multiple virus detections were correlated with less severe disease. The relationship between viral load and multiple virus infections was virus specific, and this may serve as a way to differentiate viruses in multiple virus infections.     

Nosocomial viral respiratory infections: perennial weeds on pediatric wards

The frequency and importance of nosocomial infections of the respiratory tract in pediatrics have generally been underestimated. In part this has resulted from the emphasis on bacterial infections which occur primarily in select at-risk populations. Most respiratory infections in pediatric patients, hospital- and community-acquired, are viral and all patients are potentially susceptible The epidemiologic patterns of these viral respiratory agents on the ward mirror those seen in the community in terms of frequency, season, age affected and severity of illness. Hence, the most frequent nosocomial agents are the viruses that occur in outbreaks or epidemics and cause respiratory illness, epidemic respiratory viruses--respiratory syncytial virus, which causes the greatest morbidity and mortality; influenza, and the parainfluenza viruses. Their import, as exemplified by respiratory syncytial virus, results from (1) the severity of disease produced in young children, which is magnified in those hospitalized with certain underlying conditions; (2) the abundant and prolonged viral shedding, allowing easy spread; (3) the potential susceptibility of all patients and staff, since infections recur throughout life; and (4) the difficulty in controlling nosocomial spread.