Flu and people with asthma. Centers for Disease Control and Prevention. Wu, TD, et al. Asthma in the primary care setting. The Medical Clinics of North America. Grohskopf LA, et al. Prevention and control of seasonal influenza with vaccines: Recommendations of the Advisory Committee on Immunization Practices - United States, Influenza Season. See also After a flood, are food and medicines safe to use?
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The final collection, including the previously published sequences, consisted of full-length human rhinoviruses genomes. The researchers compared all the sequences to determine how they are related. Based on these relationships, they discovered that there may be up to 4 different species of rhinovirus.
The researchers found that all the virus RNA strands feature a cloverleaf-like shape at one end. Nearly every virus had a unique sequence in a section of this region. Analogous regions in related viruses have been shown to affect how pathogenic the viruses are. The researchers believe this stretch of sequence might play a similar role in rhinoviruses. The scientists also found evidence for distantly related strains swapping sections of RNA. Exactly where and how the viruses exchange genetic material in the body is uncertain, but multiple rhinoviruses are known to infect people simultaneously.
Th2 type inflammation in the airways often starts in childhood, when environmental stimuli such as viral respiratory tract infection, exposure to parental smoking, and NO 2 and other airborne pollutants or allergens activate airway epithelial cells to produce type 2 inflammatory cytokines including IL, IL, or TSLP thymic stromal lymphopoietin Fig.
This initiates a cascade that leads to the development of childhood asthma Figs. The reason why this Th2 type response persists in some patients is not well known.
Summary of environmental factors affecting development a and exacerbations b of asthma. A Interplay of environmental air pollution, allergens, viruses and host genetic, microbiome factors shape the risk of asthma development and predispose to different asthma phenotypes. B Environmental exposures to allergens animal, pollen, mold , viruses, cigarette smoke, and air pollution are known triggers for asthma exacerbations.
Thunderstorms are associated with asthma exacerbations. Thunderstorms produce ozone and release allergen-bearing small particles that irritate airways. Avoidance of environmental exposures can improve asthma control and reduce exacerbations. Having allergic sensitization and eczema at the time of wheezing with rhinovirus are all risk factors of having atopic asthma at the age of 7 years [ 59 ].
On the contrary, having RSV as the cause of the first wheeze before the age of 1 year or exposure to parental smoking are both associated with non-atopic asthma at age 7 years [ 59 ]. A recent study showed that the risk of developing asthma was highest in infants having IgE sensitization and wheeze due to rhinovirus-C infection [ 39 ]. These results suggest that mechanisms of virus-induced illnesses differ.
The mechanisms underlying the observed associations between rhinoviruses, allergic sensitization, and the development of asthma are not fully understood. It is possible that there is a causal relationship where acute rhinovirus infection induces various cellular factors regulating host response, airway inflammation, repair, and remodeling, as well as increase proinflammatory cytokine and chemokine production Fig.
Also, rhinovirus infection and allergen exposure increase epithelial cells to produce IL and IL, thus promoting Th2 type inflammation Fig. Most likely, all of these mechanisms play a role in the development of either atopic or non-atopic asthma. Several therapeutic strategies have been shown to alter the natural history of virus-induced asthma exacerbations Fig.
In general, such treatment would need to be applied as early as possible during infection to increase the chances of success, safety, and be easy to administer. Current strategies for asthma prevention and treatment. Details in text. RV, rhinovirus; RSV, respiratory syncytial virus. The major obstacle is an antigenic diversity of the more than serotypes of rhinovirus, meaning that creating a successful vaccine is an extremely challenging task [ 66 ].
In the development of the RV vaccine, promising results have been seen with a cross-reactive recombinant capsid protein in a mouse model [ 67 ]. Recently, attention has been caught to live attenuated vaccines and subunit vaccines against RSV combined with Th1-enhancing adjuvant, although neither of them seems likely to be introduced to routine clinical practice soon [ 68 ]. The application of palivizumab resulted in a remarkably reduced risk of recurrent wheezing episodes following hospitalization due to RSV, but not asthma [ 11 ].
Interestingly, a new, second-generation high-affinity derivative of palivizumab motavizumab did not prevent long-term recurrent wheezing despite reducing the rate of severe acute RSV disease [ 69 ]. There is no convincing data supporting ribavirin treatment for severe RSV infection, while there are concerns about its toxicity. Therefore, ribavirin is neither recommended in the USA nor any European guidelines [ 70 ]. At this time, there are 17 new RSV vaccines and biologicals in a pipeline of clinical trials while another 28 are in pre-clinical development [ 68 ].
Numerous new molecules have already been characterized as capable of inhibiting RSV dissemination within the airways and are investigated as potential candidates for pre-clinical and clinical development [ 66 ]. Although it is hypothetically possible nowadays to interfere with every step of the infectious cycle of respiratory tract viruses from viral attachment, viral entry and uncoating, translation, replication, and onward to virus release , only a few approaches have met with success with RV thus far.
There is only a limited number of agents that interact with the RV attachment to the cell or uncoating of the viral RNA that have been tested in clinical trials pleconaril, amantadine, rimantadine [ 71 ].
Regrettably, their clinical applicability is continuously questioned due to adverse events pleconaril, vapendavir or drug resistance amantadine, rimantadine [ 66 ]. Two separate randomized trials exist, in which oral corticosteroid, prednisolone, has been applied to wheezing children with RV etiology.
Noteworthy, high RV genome load in the placebo-treated wheezing children was associated not only with the development of a new wheezing episode within days in every case but also with the initiation of asthma medication within the next 14 months in every case [ 72 , 73 ]. These results indicate that systemic anti-inflammatory treatment of the first RV-induced severe wheezing episode may markedly decrease the subsequent risk for asthma.
Whether RV bronchiolitis is the cause of severe lung injury, resulting in subsequent wheezing episodes and development of asthma or if there is an inborn susceptibility to both acute bronchiolitis and subsequent asthma remains still a matter of debate. Subsequently, two prospective studies with RSV immunoprophylaxis have been performed to address the potential causality between RSV infection and subsequent asthma.
In these recent randomized controlled trials, pre-term infants who received palivizumab demonstrated a decreased number of recurrent wheezing episodes, but the incidence of physician-diagnosed asthma at age 6 remained intact [ 74 , 75 ]. These effects, however, were less noticeable in infants with atopic family history, indicating that RSV infection is not causal to asthma or atopy development.
On the contrary, atopy is associated with childhood asthma inception after RV-induced bronchiolitis. A study in high-risk birth cohort parental atopy or asthma from WI, USA, has demonstrated that in young children who experienced RV-induced bronchiolitis, there is a high risk of school-age asthma OR 9. RSV , and the risk becomes even higher in children sensitized at an age younger than 2 [ 7 , 76 ].
Another study from Turku, Finland, shows strikingly similar results. In infants at the age of less than 2 years, who developed RV-induced bronchiolitis, the odds ratio for atopic asthma at school age was 5. RSV-induced bronchiolitis was neither associated with atopic nor non-atopic asthma [ 59 ]. Protection of these high-risk children against the effects of severe respiratory infections during infancy may represent an effective strategy for primary asthma prevention.
Exacerbations usually occur in response to a variety of external agents, including respiratory viruses, bacteria, allergens, air pollutants, smoke, and cold or dry air Fig. However, most viral infections are not associated with acute exacerbations, and cofactors, including bacterial and allergic inflammation, have been described to increase the severity of exacerbation Fig. The most common viral triggers for asthma exacerbation are rhinoviruses, particularly subtypes A and C [ 15 ].
Hospital admissions for asthma exacerbations correlate with a seasonal increase of RV infections in autumn from September to December and again in spring [ 15 , 78 ]. Other respiratory viruses may also cause exacerbations. Respiratory syncytial virus RSV , which frequently causes wheeze in infants and young children, can also trigger acute asthma exacerbation in adults [ 79 ].
Human metapneumovirus, influenza, parainfluenza, adenovirus, coronavirus, and bocavirus have all been detected in asthma exacerbations but in lower frequencies [ 3 ]. Several mechanisms why asthmatics are predisposed to viral infections have been proposed. One of the proposed reasons is damaged epithelium, which may increase susceptibility to infection and ultimately lead to airway obstruction Fig.
Interestingly, the corresponding gene for CDHR3 has been linked to childhood asthma with severe asthma exacerbations [ 32 ]. Airway epithelial cells form a barrier to the outside world and are the front line of mucosal immunity Fig. Cytokines and inflammatory mediators associated with allergic inflammation induce epithelial barrier disruption. Additional factors that influence the severity of the viral infection and the risk of asthma exacerbation are allergic sensitization and the airway microbiome.
For example, RV infection and allergic sensitization synergistically increase the risk of exacerbation [ 3 ]. Atopic asthma with allergic sensitization can be associated with reduced virus-induced IFN responses, increased viral shedding, and decreased viral clearance [ 3 ].
Studies with omalizumab, anti-IgE, have shown that neutralizing IgE-mediated inflammation can enhance IFN responses and reduce virus-induced asthma exacerbations in children [ 84 ]. This finding suggests that neutralizing IgE indirectly improve anti-viral responses.
Several studies have shown that viral infections precede bacterial infections in airways. This phenomenon may occur due to several reasons; viruses may induce expression of airways receptors used by bacteria, viruses may disrupt epithelial barrier, and they increase the release of inflammatory cytokines and mediators causing increased inflammation and risk of asthma exacerbations Fig.
In addition, patients with asthma are frequently colonized with bacteria in lower and upper airways [ 48 ], and acute wheezing in infants has been associated with both viral infections and airway microbiota dominated by bacterial pathogens [ 50 ]. Bacterial infections may impair mucociliary clearance and increase mucus production. However, evidence linking bacterial infections to acute asthma exacerbation is limited.
Exacerbations of asthma are characterized by a progressive increase in symptoms of shortness of breath, cough, wheezing, and progressive decrease in lung function.
Viral respiratory infections remain a leading cause of asthma exacerbations, both in children and adults. The presence of any pathogen is usually associated with a higher risk of treatment failure [ 86 ]. Typically management of all asthma exacerbations includes a symptomatic treatment increasing doses of beta 2-agonists, enhancing the use of inhaled or oral glucocorticosteroids [ 87 ]. Glucocorticosteroids are by far the most widely used drugs in children with asthma and have potent anti-inflammatory activity.
In recent years, an increasing body of pre-clinical evidence supports their use in combination with long-acting beta-agonists, such as salmeterol and formoterol, and highlights the superiority of combination therapy in asthma exacerbations over either drug alone. The effective suppression of growth factors highlighted above certainly represents a plausible mechanism through which these drugs might inhibit virus-driven inflammation and remodeling.
Surprisingly, systemic anti-IgE treatment was also shown to markedly reduce infection-induced severe asthma exacerbations. A year-round treatment with omalizumab has been shown to abolish the seasonal peaks in asthma exacerbations, most of which are associated with RV infection [ 84 ]. Influenza contributes to some acute asthma exacerbations. Children with asthma should remain a priority group for influenza immunization because of the newly established association between influenza and ED management failure combined with well-recognized influenza-related complications [ 88 ].
This recommendation has been ultimately confirmed by a recent systematic review and meta-analysis, showing that influenza vaccination reduced the risk of asthma exacerbations [ 22 ].
Pidotimod is a synthetic thymic dipeptide that appears to share several mechanistic similarities with bacterial immunomodulators, and it is thought to stimulate toll-like receptor 2 TLR2 and TLR4, which are expressed on DCs, this displaying anti-infective effects. To date, there is only one prospective multicenter trial, showing that pidotimod reduced the number of respiratory infections in a mixed group of children over half of whom had atopic conditions, including asthma [ 90 ].
Bacterial lysates have recently been proved to reduce the number of the recurrent wheezing episodes and asthma episodes, in patients treated with BL compared with placebo 5 trials [ 91 ].
However, higher-quality trials are required before firm conclusions can be drawn regarding the prophylactic efficacy of bacterial lysates in asthma. There are several novel approaches, being tested in laboratories and clinical research for their ability to target RV-induced infection. All of them, however, show only marginal benefit in symptoms, viral replication, and development of clinical symptoms of colds, while exhibiting substantial side effects [ 71 ].
Using viral markers in relation to treatment might be a good strategy to prevent asthma. Here we suggest that prevention and treatment of recurrent wheezing may in the foreseeable future be based on virological tests at the first episode of wheezing. Determine Eligibility. Prepare Your Application. Additional Application Elements. Research with Special Considerations. Submit an Application. Track Your Application.
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