1.Virus infection
Virus is both an infection source and an allergen, which is an important factor leading to the occurrence of asthma. The mechanism of virus-induced asthma is mainly manifested as
(1) Viral infection can induce the infiltration and activation of inflammatory cells such as eosinophils in the airways, and increase the infiltration of inflammatory cells by promoting the expression of chemokines such as RANTES and intercellular adhesion molecule (ICAM)-1 by epithelial cells.
(2) Promote the release of inflammatory mediators from inflammatory cells;
(3) Virus acts as an allergen to promote IgE synthesis; (4) Direct damage to the airways by respiratory viral infections, disrupting the integrity of the airway epithelium and increasing the chances and extent of airway sensitization. However, different viral infections resulting in hairy branches can have different incidence of asthma.
Respiratory syncytial virus (RSV) is the most common pathogen of capillary bronchitis, accounting for 50-70% of cases, and is most common in infants aged 2-6 months. gross branch of RSV infection is the most common cause of first wheeze in infants, and there is a close association between gross branch and the occurrence of recurrent wheeze and asthma in infants and children. Data show a significant increase in the probability of recurrent wheezing and asthma in children after RSV hairy branch. A long-term large sample follow-up data from Tuscon [5] in the United States showed that children with early RSV lower respiratory tract infection had a significant increase in persistent wheezing episodes at age 6 years, but these episodes decreased with age and this correlation disappeared by age 13 years; Sigurs N et al [6] conducted a 7-year follow-up of children hospitalized with early postnatal RSV infection with hairy branch (mean age 4 months). Gross branch of RSV was found to be an independent high risk factor for the subsequent development of recurrent wheezing and asthma (OR: 12.7, 95% CI 3.4 – 47.1), with a cumulative prevalence of asthma of 30% , 3% (P<0.001) and cumulative occurrence of wheezing of 68% , 34% (P<0.001) in the gross branch group and control group, respectively, after 7 years. A 19-year follow-up data [7] showed that the prevalence of asthma was 30% in the hairy group compared to 11% in the control group. Other viruses such as parainfluenza virus and influenza viral Mauve subsequently have asthma prevalence similar to RSV.
Rhinovirus (RV) is another virus that deserves our clinical attention as it is not only the most common agent of upper respiratory tract infections in older children and adults, but recently there is increasing evidence that RV can cause lower respiratory tract infections, including Mauve in infancy, and it has been reported that RV is second only to RSV in causing acute Mauve [8]. One study compared asthma after RSV and RV hairy branch, and the prevalence of asthma in the RV group was as high as 60% at a mean follow-up of 6 years, while the prevalence of asthma in the RSV hairy branch group was only 10%, suggesting that RV infection is more likely to cause asthma in childhood than RSV infection, so it has been suggested that RV infection with hairy branch may be the first sign of asthma [9].
In recent years, human parapneumovirus was also found to be a common pathogen of hairy branch, and et al [10] showed that human parapneumovirus was in second place after RSV in the detection of hospitalized children with lower respiratory tract infection under 2 years of age in Spain, but the relationship of parapneumovirus to later wheezing attacks and asthma has to be preceded by long-term follow-up later.
2.Genetic factors
Heredity is one of the basic causative factors in the development of asthma and an important influencing factor in the progression of hairy branch to asthma. If one parent suffers from allergic diseases, 25%-35% of the offspring will suffer from allergic diseases, and if both parents suffer from allergic diseases, the chance of the offspring suffering from allergic diseases rises to 40%-60%. Moreover, parental illness at a young age is associated with the early development of wheezing disease in offspring, and according to Tuscon, USA [5], a history of asthma or hairy branch in parents before the age of 3 years is a high risk factor for the early development of wheezing lower respiratory tract infections in their offspring (OR: 2.6; p<0.05). Prevalence data also show that children with a family history of allergy or asthma have a 54% prevalence of asthma at 3 years after infection with RSV Mao, which is significantly different compared to RSV Mao without a family history [11], suggesting some family aggregation. Some progress has been made in genetic studies, but there is no reliable genetic marker that can predict asthma occurrence, and further studies are needed.
3. Individual atopy.
Allergic status in infancy (positive skin allergen prick test, increased blood IgE, increased peripheral blood eosinophilia, etc.) or history of atopic dermatitis, eczema, atopic conjunctivitis, allergic rhinitis, etc. is a high risk factor for the development of asthma. Children with hairy branch with these manifestations are more likely to develop asthma later in life.
There is a correlation between RSV infection and atopic constitution, on the one hand, RSV infectivity is more likely to occur in children with underlying atopic constitution, and one study [12] found that in children with Mao Bronchitis there was a low level of IL-12 in cord blood before infection, and there was a significant difference compared to infants who did not develop Mao Bronchitis (295 Vs 507 pg/ml, p=0.001), IL-12 promotes TH0 to TH1 development, low IL-12 resulted in low TH1 function and TH2 dominant immune response. On the other hand, RSV infection induces the development of individual atopy, and Pala et al [13] found that children with RSV infection during infancy had a local IL-4 enriched microenvironment at the age of 7-8 years, while IL-4 enhanced the ability of T cells to respond to RSV and other allergens and increased allergen sensitivity. It has also been reported that the skin allergen prick test and specific IgE test were performed on children with hairy branch at the age of 3 and 7 years, and the allergen sensitivity of the hairy branch group was significantly higher than that of the control group.
4. Immunological abnormalities
The immune system of the normal born neonate is not yet mature, and the immaturity of the APC system renders the TH1 selection mechanism ineffective. During the antigen presentation phase, IL-12 production is minimal. The lack of effective TH1 differentiation stimulating factors leads to a cellular response in favor of Th2. Especially in early infancy, the TH2/IgE response can be perpetuated if influenced by environmental factors (viral infection or stimulation by allergens), causing immune memory to be restricted to the TH2 subpopulation. This predisposes these infants to allergic diseases and asthma.
Not only is there a TH1/TH2 immune response imbalance in RSV gross branches, but RSV infection can lead to increased secretion of chemokines [14], such as increased RANTES and MIP-1α, IL-8, which have significant chemotactic and activating effects on lymphocytes, eosinophils, and neutrophils.Our previous animal studies all showed that RANTES, MIP-1α, and IL-8 play an important role in the pathogenesis of asthma [15, 16], thus RSV infection promotes airway inflammation and airway hyperresponsiveness.
5, Environmental influence
The environment is another important contributing factor to the progression of hairy branch to asthma. Infectious inflammation of the airways caused by viral infection disrupts the integrity of the airway mucosal epithelium and weakens the defenses against allergens and irritants, increasing the chance and extent of airway sensitization, which can lead to the development of atopic symptoms, especially in those immune susceptible children. Children exposed to allergens within the first 2 years of life are more likely to develop asthma in childhood than those exposed after 2 years; and prophylactic reduction of house dust mite exposure from birth reduces the incidence of asthma and allergy in school-age children [17]. Environmental factors also act through genetic factors, and different environmental factors influence the genetic susceptibility to asthma and allergic reactions by increasing or decreasing the epistasis of susceptibility genes.
Passive smoking has been shown to be an important trigger for the development of asthma, and maternal history of smoking during pregnancy and passive smoking after birth is significantly associated with the development of asthma and allergic diseases in offspring, especially as a high risk factor for the development of wheezing and asthma within 6 years of age [18]. Thus environmental and other related factor exposure during fetal and infancy plays a key role in the development of asthma.
6. Feeding practices
Infant feeding practices also play an important role in the development of allergic reactions and asthma. Breastfeeding infants can reduce the occurrence of asthma and allergic diseases later in life, and human milk contains a large number of active immune factors such as SIgA, active lysozyme and lactoferrin, which can enhance the infant’s ability to resist disease, so it is currently advocated that infants under 6 months of age are exclusively breastfed. However, it has been recently reported that this may not be the case for atopic mothers and children. Wright et al [19] found that exclusive breastfeeding for 4 months or more in infants with atopic (positive skin spot allergen prick test) and mothers with a history of asthma increased the prevalence of asthma at 6 years of age (OR 8.7, 95% CI 3.4-22.2).
7. Other
In addition to the above aspects, there are many factors that can influence the progression of hairy branch to asthma. For example, prematurity and low birth weight infants are themselves a risk factor for viral infections and also for promoting atopy. Prepubertal male infants are also a risk factor for the development of asthma. Pre-onset infants with low lung function are significantly more likely to develop chronic lower respiratory disease after viral infection. A prospective study showed that most of those with low lung function within 3 years of age developed asthma in early adulthood [20], so early lung function testing can predict asthma onset to some extent.
Clinical predictors of the development of wheezing to asthma in infants and children
Post-hairy branch can cause recurrent wheezing in infants and children, and there are three main clinical types of infant wheezing according to Tuscon, USA [5]. Transient infantile wheeze: wheezing occurs within 3 years of age and no wheezing episodes after 3 years of age; non-allergic wheeze: lower respiratory tract infection with wheezing occurs within 3 years of age and wheezing episodes still occur after 3 years of age, also known as persistent wheezing, this type of child has an allogeneic gene, about 60% of children develop atopy by 6 years of age, 40% do not develop atopy; allergic wheeze: many children who develop allergic asthma. Their first wheeze appears before 6 years of age and can be divided into 2 subtypes:
(1) early-onset allergic wheeze, previously known as persistent wheeze, which appears within 3 years of age.
(2) Late onset allergic wheeze, formerly known as late onset wheeze, which occurs after 3 years of age.
Whether wheezing that appears within the first 3 years of life later develops into asthma, castro-rodriguez et al [21] analyzed six parameters (frequency of wheezing, history of eczema, history of parental asthma, allergic rhinitis, eosinophilia, wheezing caused by non-supine sensation) that are more easily available to clinicians and proposed an assessment of asthma predictors, see Table 1
Table 1: Clinical indicators of asthma risk
Primary indicators
Secondary indicators
1 Physician diagnosis of parent with asthma
2 Physician diagnosis of infant with eczema
3 Physician diagnosis of the infant with allergic rhinitis
4, wheezing caused by non-supine sensation
5, EOS ≥ 4%
Strict predictor: early recurrent wheezing (3 or more wheezing episodes) with 1 of 2 major indicators or 2 of 3 minor indicators
Loose predictor: early wheezing episodes with 1 of 2 primary indicators or 2 of 3 secondary indicators
Children with wheezing who met the loose predictors were 2.6-5.5 times more likely to develop asthma by 6-13 years of age than those who did not, with approximately 59% developing asthma by school age, while those who met the strict predictors were 4.3-9.8 times more likely to develop asthma by 6-13 years of age than those who did not, with approximately 76% developing asthma by school age In infants with wheezing who do not have the above strict predictive index, the chance of developing asthma is <5%. Therefore, this can be used clinically as a predictor of the development of asthma in infants and children with wheezing. < p="">In summary, the development of post-hairy asthma is influenced by a number of factors, and the chart by Openshaw PJ et al [22] clearly shows these associations in comparison. A proper understanding of the diagnostic features of asthma in the youngest years and the use of asthma expectancy indicators for the assessment of children with wheezing and timely intervention in children at risk can help stop the onset of asthma.