Viruses and asthma: Inception, exacerbation, and possible prevention

doi:10.1067/mpd.2003.19

The Journal of Pediatrics

Volume 142, Issue 2, Part B, February 2003, Pages S3-S8

https://doi.org/10.1067/mpd.2003.19 Get rights and content

Abstract

Viral respiratory tract infections have been epidemiologically associated with asthma in at least 3 ways. First, during infancy, certain viruses have been implicated in the inception of the asthmatic phenotype. Second, in patients with established asthma, particularly children, viral upper respiratory tract infections play a significant role in producing acute exacerbations of airway obstruction, often resulting in outpatient visits or hospitalizations. This increased propensity of viral infections to produce lower airway symptoms in asthmatic persons may be related, at least in part, to interactions among allergic sensitization, allergen exposure, and viral infections—all acting as cofactors in the induction of acute episodes of airflow obstruction. Third, and perhaps counterintuitively, certain infections may actually prevent the development of allergic respiratory tract diseases, including asthma. This review discusses these associations as they pertain to both the pathogenesis and treatment of childhood asthma. (J Pediatr 2003;142:S3-S8)

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Cited by (56)

Leukotriene receptor antagonist attenuated airway inflammation and hyperresponsiveness in a double-stranded RNA-induced asthma exacerbation model
2017, Allergology International
Citation Excerpt :
Viral infections in the respiratory tract are the most common triggers of an acute asthma exacerbation.1
Viral infections are the most common triggers of asthma exacerbation, but the key molecules involved in this process have not been fully identified. Although cysteinyl leukotrienes (cysLTs) have been postulated as the key mediators, their precise roles remain largely unclear. To investigate the roles of cysLTs in virus-induced asthma exacerbation, we developed a murine model using a viral double-stranded RNA analog, polyinosinic–polycytidylic acid (poly I:C), and analyzed the effect of leukotriene receptor antagonist (LTRA) administration.
A/J mice were immunized with ovalbumin (OVA) + alum (days 0, 28, 42, and 49), followed by intranasal challenge with OVA (phase 1: days 50–52) and poly I:C (phase 2: days 53–55). Montelukast was administered during poly I:C challenge (phase 2) in the reliever model or throughout the OVA and poly I:C challenges (phases 1 and 2) in the controller model. Airway responsiveness to acetylcholine chloride was assessed, and bronchoalveolar lavage (BAL) was performed on day 56.
Administration of poly I:C to OVA-sensitized and -challenged mice increased the number of eosinophils and levels of IL-13, IL-9, CCL3, and CXCL1 in BAL fluid (BALF) and tended to increase airway responsiveness. Montelukast significantly attenuated the poly I:C-induced increase in the number of eosinophils and levels of IL-13, IL-9, and CCL3 in BALF and airway hyperresponsiveness in both the reliever and controller models.
This is the first report showing that LTRA functionally suppressed the pathophysiology of a virus-induced asthma exacerbation model, suggesting the importance of cysLTs as a potential treatment target.
Serious Early Childhood Wheezing After Respiratory Syncytial Virus Lower Respiratory Tract Illness in Preterm Infants
2010, Clinical Therapeutics
Citation Excerpt :
In this theory, no single factor dominates any other in determining outcome. Although the strongest association between viral lower respiratory tract infection and subsequent development of wheezing has been noted with RSV, there have been reports of other viral infections, such as rhinovirus, influenza virus, and parainfluenza virus, that triggered subsequent wheezing.28–30 One approach to delineating whether the pathway is causal or RSV-specific would be to demonstrate a reduction in long-term airway morbidity by reducing RSV in infancy.
Respiratory syncytial virus (RSV) lower respiratory tract infection (LRI) in early life has been associated with sustained airway hyperreactivity during childhood; however, corresponding data in premature infants are sparse.
The objective of this study was to determine whether RSV-LRI during early infancy of preterm infants was associated with an increased risk for serious early childhood wheezing (SECW) by age 3 years.
A retrospective cohort study was conducted using data from a large (∼14 million members) US health plan database. The study population included infants ≤6 months of age born at ≤36 weeks' gestational age or weighing <2500 g, or both. Preterm infants with any medically attended RSV-LRI from May 2001 through April 2004 with 3 years of continuous eligibility were selected and propensity matched with ≤3 control infants. SECW was defined as >3 office, outpatient, or emergency department (ED) visits with asthma or wheezing; ≥1 office, outpatient, or ED visit with asthma or wheezing plus treatment with systemic corticosteroids within 7 days; ≥1 inpatient stay with asthma or wheezing; or ≥150 days' supply of asthma-control medications. The presence of SECW between ages 2 and 3 years was compared between infants with and without RSV-LRI using univariate and multivariate methods. Health care costs for patients with SECW were explored.
A total of 378 infants with RSV were matched to 606 controls. The prevalence of SECW between ages 2 and 3 years was 16.7% in the RSV-LRI group versus 8.6% in the control group (P < 0.001). Logistic regression showed that preterm infants with RSV in early life were 2.52-fold (95% CI,1.65–3.85) more likely to present with SECW between ages 2 and 3 years (P < 0.001). Patients with SECW had a mean SECW-related cost of US $1378 (95% CI, $939–$1816) and total health care cost of $7138 (95% CI, $5087–$9189) compared with $37 (95% CI, $24–$51) and $2521 (95% CI, $1789–$3253), respectively, for patients without SECW. After adjusting for possible confounders, patients with SECW had a significantly higher total health care cost than did patients without evidence of SECW (P < 0.001).
The development of RSV-LRI in infancy in preterm infants was associated with an increased prevalence of SECW between ages 2 and 3 years. Patients with SECW had higher total health care costs than those who did not have SECW.
Changes in weather and the effects on pediatric asthma exacerbations
2009, Annals of Allergy, Asthma and Immunology
Citation Excerpt :
Currently, 9 million US children younger than 18 years have been diagnosed as having asthma.4,5 Viral infections,6 tobacco smoke exposure,7 aeroallergens,8 and air pollutants9 have been shown to trigger pediatric asthma exacerbations. Parents and patients often attribute worsening asthma symptoms and exacerbations to “changes in the weather.”
Pediatric asthma exacerbations may correlate with changes in weather, yet this relationship is not well defined.
To determine the effects of fluctuations in climatic factors (temperature, humidity, and barometric pressure) on pediatric asthma exacerbations.
A retrospective study was performed at 1 large urban hospital during a 2-year period (January 1, 2004, to December 31, 2005). Children presenting to the emergency department (ED) for an asthma exacerbation were included. Data on climactic factors, pollutants, and aeroallergens were collected daily. The relationship of daily (intraday) or between-day (interday) changes in climactic factors and asthma ED visits was evaluated using time series analysis, controlling for seasonality, air pollution, and aeroallergen exposure. The effects of climactic factors were evaluated on the day of admission (T = 0) and up to 5 days before admission (T − 5 through T − 1).
There were 25,401 asthma ED visits. A 10% intraday increase in humidity on day T − 1 or day T − 2 was associated with approximately 1 additional ED visit for asthma (P < .001 and P = .01, respectively). Interday changes in humidity from day T − 3 to T − 2 were also associated with more ED visits (P < .001). Interday changes in temperature from T − 1 to T = 0 increased ED visits, with a 10°F increase being associated with 1.8 additional visits (P = .006). No association was found with changes in barometric pressure.
Fluctuations in humidity and temperature, but not barometric pressure, appear to influence ED visits for pediatric asthma. The additional ED visits occur 1 to 2 days after the fluctuation.
The role of viruses in the development and exacerbation of atopic disease
2009, Annals of Allergy, Asthma and Immunology
Citation Excerpt :
Articles were selected for their relevance to viruses and their role in asthma. In reviewing the literature, we noted that there are essentially 3 avenues of viral asthma research: data supporting a role for viruses in the development of asthma, data focused on the role of viruses in asthma exacerbations, and data supporting a role of viruses in causing atopy.2 Evidence favoring a causative role for viral infections in asthma development includes studies focused on specific viruses, as well as several epidemiologic studies that have documented a role for viral exposure factors, such as day-care and family size.
To examine data in support of the viral hypothesis of atopic disease.
We retrieved review articles and original research from MEDLINE, OVID, and PubMed (1950-June 2009) that addressed our topic of interest, using the terms respiratory virus, asthma, IgE, atopy, and viral-induced wheeze.
Articles were selected for their relevance to viruses and their role in asthma.
Much of the data in support of the viral role in asthma focuses on rhinovirus and respiratory syncytial virus. Epidemiologic studies have used factors such as day-care and family size as surrogates for infection in studies that support and negate the role of viruses in the development of asthma. A large volume of literature supports the theory that virus exacerbates preexisting asthma by setting off the inflammatory cascade. No mechanistic studies fully explain how viral infections can translate or exacerbate atopic disease. We provide information from our mouse model that suggests that dendritic cells, IgE, and FcɛRI are critical to the induction of atopy. Studies of patients taking antiviral agents (eg, ribavirin or palvizumab) support the notion that interfering with respiratory viral infections may decrease the development of atopy.
Many studies suggest strongly that viral infections may predispose patients to the development of asthma and other atopic diseases. Further, mechanistic studies are necessary to allow for the development of targeted therapeutics to prevent the translation of viral into atopic disease.
RESPIRATORY SYNCYTIAL VIRUS
2009, Feigin and Cherry's Textbook of Pediatric Infectious Diseases, Sixth Edition
Influenza vaccination and childhood asthma
2008, Vacunas

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^☆: Supported by National Institutes of Health grants 1PO1AI50500, 2P50H L56396, and 1RO1HL61879.

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Proceedings from the Consensus Conference on the Treatment of Viral Respiratory Infection-Induced Asthma in Young ChildrenViruses and asthma: Inception, exacerbation, and possible prevention☆

Abstract

Proceedings from the Consensus Conference on the Treatment of Viral Respiratory Infection-Induced Asthma in Young Children
Viruses and asthma: Inception, exacerbation, and possible prevention☆