Download Virusinduced wheezing and asthma

Virusinduced
wheezing and asthma
Dr. Hala al refai
Damascus Hospital
• Viral respiratory infections, particularly with
respiratory syncytial virus (RSV)
• and human rhinovirus (HRV), are the most
common causes of wheezing in infants and
young children
• and are common triggers of asthma
exacerbations in patients with preexisting
asthma
• In addition,
• wheezing with viral illnesses in infants and
young children is associated with an increased
risk of childhood asthma
PATHOGENESIS
• Viral respiratory infections interact with host
factors to promote virus induced wheezing
and asthma exacerbations
• Respiratory symptoms with viral infections
• probably result from virus induced damage of
the airway epithelium, followed by airway
inflammation in a predisposed individual.
• Immune responses triggered by viral
respiratory tract infections include
• enhanced allergic inflammation, increased
granulocyte recruitment, promotion of
cytokine production
• Respiratory viruses, such as influenza and RSV
cause cytopathic damage to airway epithelium
and these changes can affect the function of
the epithelium and airway smooth muscle.
• In addition, disturbing the integrity of the
epithelial layer may enhance mucosal
permeability and increase exposure of
inflammatory and antigen presenting cells to
allergens
• Rhinoviruses, in contrast to other respiratory
viruses, do not damage the epithelium.
• However, rhinovirus and other respiratory viruses
can activate epithelial cells to upregulate the
expression of ICAM1 receptors, enhancing
replication of HRV.
• They also induce epithelial cells to secrete a wide
variety of chemokines and cytokines, including
interleukin (IL)6, IL8 (CXCL8), IL11,
• and RANTES (CCL5), a chemo attractant for
eosinophils, monocytes, and T cells
• Respiratory viral infection and replication activate
innate and adaptive antiviral immune responses,
resulting in proinflammatory cytokine and
chemokine production and the recruitment of
inflammatory cells to the airway.
• Rhinovirus has shown few cytopathic effects on
airway epithelium or other tissues in contrast to
other respiratory viruses, such as RSV and
influenza
• These observations raise the possibility that
rhinovirus can induce and promote airway
inflammation by its interaction with airway
cells and the subsequent stimulation of
cytokine production
• Experimental infections with rhinovirus lead
to increased airway responsiveness, enhanced
inflammatory responses, a higher likelihood
for the development of the late allergic
reaction, and eosinophil recruitment to the
airway following antigen challenge.
• Two studies found increased airway
responsiveness to histamine and
augmentation of both the
• immediate and late phase responses to
inhaled allergen following experimental
rhinovirus infection in patients with allergic
rhinitis
• In one of these reports, rhinovirus infection
enhanced the allergic inflammatory reaction
in the lower airway, as demonstrated by
increased recruitment of eosinophils to the
airway following segmental antigen challenge
• Increased submucosal lymphocytes and
epithelial eosinophils are demonstrated
on biopsy of the lower airway during
rhinovirus colds that are associated with
increased airway responsiveness to
histamine
• Granulocytes — Neutrophils are the principal
cells recruited to the airways during the acute
phase of a viral infection and are also
recruited to the lower airways during
experimental rhinovirus infection
• During acute viral illness, HRV infected adults
with asthma have increased recruitment of
neutrophils compared with HRV infected
adults without asthma
• This response is, in part, regulated by IL8
• (CXCL8) and leukotriene B4 (LTB4)
• Macrophages and monocytes — Airway
macrophages are the predominant airway cell
and are probably involved in host responses to
respiratory viruses.
• Nasal secretions obtained during upper
respiratory tractinfections contain
• IL1,
• tumor necrosis factor (TNF)alpha,
• and IL8
• These cytokines are important in the
development of acute symptoms, such as
fever and myalgia.
• In addition, these mediators can stimulate
epithelial cells to express adhesion molecules
• Parasympathetic hyper responsiveness In animal
studies, other mechanisms have been identified
to explain changes in airway function during viral
respiratory infections.
• Two studies in guinea pigs and rats
• found that viral respiratory infections impair
inhibitory M2 muscarinic receptor function,
producing
• parasympathetic hyper responsiveness that leads
to broncho constriction
• Increased IgE
• One study demonstrated increases in IgE
levels in subjects with allergic rhinitis,
• but not in subjects with nonallergic rhinitis
after experimental rhinovirus infection
• Other investigators
• have shown that RSV and parainfluenza virus
can stimulate total IgE and virusspecific IgE in
children
• The development of virusspecific IgE levels
correlates with the probability of recurrent
episodes of wheeze
WHEEZING DUE TO VIRAL INFECTION
• Studies have shown that viral infections
trigger up to 85 % of asthma exacerbations in
school aged children
• and up to 50 % of exacerbations in adults
• Children <2 years of age — A first episode of
wheezing in association with a viral respiratory
infection leads to an outpatient visit for about
15 % of all infants in the United States,
• and 3 % are hospitalized with this
presentation
• Bronchiolitis, or inflammation of the
bronchioles, is a clinical syndrome
characterized by wheezing, tachypnea, and
hyperinflation of the lungs
• It is of
• primary importance in infants and young
children less than two years of age
• RSV is the most common cause of bronchiolitis
and wheezing in this age group.
• examined the causative factors for acute
wheezing in infants and children presenting to
the emergency department
• RSV was the most common infectious agent
found in children less than two years of age,
and the affected children were nonallergic
• Rhinovirus is also a common cause of
wheezing and bronchiolitis in infancy,
although its prevalence in virus induced
• wheezing is more significant in adults and
children older than two years of age
• The HRVC serotypes, in addition to HRVA
• and HRVB, are associated with virusinduced
• wheezing and asthma exacerbations in
children
• Metapneumovirus, another member of the
Paramyxoviridae family, can cause upper and
lower respiratory tract infection and wheezing
in young children
• Coronaviruses, bocaviruses, and influenza can
also provoke wheezing
DEVELOPMENT OF ASTHMA
• Viral respiratory infections in infancy,
particularly with RSV and HRV, are predictive
of the development of asthma in later
childhood
• In addition,
• the timing of birth and the subsequent
exposure to peak bronchiolitis and RSV season
may influence the development of asthma
• Respiratory syncytial virus — In infants and
children less than two years of age, respiratory
infections with respiratory syncytial virus (RSV)
are the most common cause of virusinduced
wheezing.
• Many of these children have decreased wheezing
during viral infections as they grow older,
although RSV infections are viewed as a potential
contributor to the development of asthma
• Those children that have persistent symptoms
of asthma or that develop asthma after RSV
infection usually have other asthma risk
factors, such as a maternal history of asthma
and elevated IgE levels
• Rhinovirus (the common cold virus) influences
the development of asthma
• Studies have shown that infants who wheeze
with rhinovirus infection have increased risk of
recurrent wheeze and asthma at ages three,
five, and six
ASTHMA COMPLICATED BY VIRAL
INFECTION
• Viral respiratory infections are an important,
• and probably the most common, cause of
increased pulmonary symptoms in children
and adults with preexisting asthma
• Rhinovirus is the predominant pathogen
identified in school aged children and adult
patients with acute asthma exacerbations.
• Infection with rhinovirus group C is associated
with more severe disease in children admitted
for asthma exacerbations
• Asthma exacerbations — Viral upper
respiratory infections (URIs or colds) are the
most frequent cause of asthma exacerbations.
SUMMARY
• Viral respiratory infections, particularly with
respiratory syncytial virus (RSV) and human
rhinovirus (HRV), are the most common causes of
wheezing in infants and young children and they
have important influences on the development of
asthma.
• In addition, viral infections, most often with
rhinovirus, are the most common causes of
wheezing or increased symptoms in patients with
preexisting asthma.
• Respiratory viruses interact with host factors
to promote virusinduced wheezing and
asthma
• exacerbations via a number of mechanisms
including increased recruitment of
inflammatory cells, promotion of cytokine
production, enhancement of
allergic inflammation, and augmented
• airways Hyper responsiveness
• Respiratory syncytial virus (RSV) is the most
common cause of bronchiolitis and wheezing
in children <2 years of age.
• Exposure to tobacco smoke and reduced lung
function are risk factors associated with
virusinduced wheezing in this age group.
• Wheezing with viral respiratory infections,
particularly with RSV and HRV, are important
predictors of the subsequent development of
asthma.
• However, it is unclear whether certain viral
espiratory infections cause asthma or if
wheezing with these infections is a predictor
of childhood asthma.
• Viral respiratory infections are an important, and probably
the most common, cause of increase pulmonary symptoms
in children and adults with preexisting asthma.
• Rhinovirus is the predominant pathogen and the most
frequent trigger of virusinduced asthma exacerbations in
patients with asthma.
• Patients with asthma do not appear to be more susceptible
to rhinovirus infection than healthy controls.
• However, they are at greater risk of developing more
severe and prolonged lower respiratory tract symptoms
with infection
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