A. Wheezing is a common respiratory symptom in infants and children
Wheezing is a common symptom of lower respiratory tract diseases in infants and young children. The pathological basis of wheezing is due to inflammation of the fine bronchi, mucous membrane congestion, edema, increased mucus secretion, and mucus embolism, which narrow the airway. Because the airway is not yet well developed, wheezing often recurs in infants and young children.
Most episodes of wheezing in infants and children are associated with viral infections of the respiratory tract, most commonly rhinovirus, coronavirus, respiratory syncytial virus, influenza virus, and parainfluenza virus. It has been found that some infants and children may have only a single, mild episode of wheezing lasting 2-3 days, often due to capillary bronchial inflammation from the first respiratory viral infection. Other infants and children may have wheezing episodes every time they get a cold.
Second, infants and children repeated wheezing is not always bronchial asthma
Some experts believe that bronchial asthma should be considered after excluding other wheezing diseases such as foreign bodies, and advocate early hormone inhalation treatment for infants and young children. In fact, recurrent wheezing in infants and children is not always bronchial asthma. Recurrent wheezing is one of the main diagnostic criteria for bronchial asthma, but not all recurrent wheezing in children is bronchial asthma. There is evidence that there are several types of respiratory syndromes in children characterized by recurrent wheezing, some of which are much shorter in duration than bronchial asthma, with virus-associated wheezing being one of the main types.
The most common form of virus-induced wheezing is respiratory syncytial virus (RSV) capillary bronchitis, which is often characterized by reactive airway disease with recurrent wheezing or asthma-like symptoms after recovery and is also a risk factor for the development of bronchial asthma. However, recurrent wheezing following RSV capillary bronchitis is not always bronchial asthma; RSV capillary bronchitis is a major risk factor for asthma formation, but the risk decreases with the age of the child, and wheezing due to RSV infection can last for more than 5 years. Therefore, many scholars believe that although recurrent wheezing can occur after RSV capillary bronchitis, only a minority of children develop asthma during adolescence.
In addition to RSV, other viruses can cause recurrent wheezing, and most children with wheezing episodes within 3 years of age have a good prognosis. About 1/3 of children have recurrent wheezing, but 60% of these children have no further wheezing by age 6. The lung function of this group of children is lower than normal before the onset of respiratory disease, in contrast to the early normal lung function of those children who continue to wheeze into adolescence. The likely reason for this is that these children are born with small airways that are prone to wheezing due to airway obstruction after viral infection, and as their airways mature with age, the chance of wheezing decreases accordingly.
Virus-associated wheezing and bronchial asthma may have different pathophysiological mechanisms, and the study by Kuehni et al. confirmed that children with wheezing symptoms in the first year of life have different lung function than children without respiratory symptoms before they develop respiratory symptoms, so early lung function decline can be used as a predictor of early transient wheezing. In addition, viral-associated wheezing has a different airway inflammatory cellular response than bronchial asthma. Biopsies of children with bronchial asthma revealed features consistent with typical pathological changes of bronchial asthma, such as increased eosinophils. In contrast, studies of bronchoalveolar lavage fluid suggest that although virus-induced wheezing has an increased total cell count as in bronchial asthma, it is mainly characterized by an increase in neutrophils and macrophages.
The differential diagnosis of wheezing in infants and children is difficult because virus-associated wheezing is similar to bronchial asthma in terms of symptoms and altered lung function. If the definition of bronchial asthma is reversible airway obstruction, then these children with wheezing symptoms at the time of infection that disappear between episodes fit this definition. If bronchial asthma is defined as an allergic airway disease, the diagnosis of bronchial asthma is not met because few of these children have allergic conditions. In addition the diagnosis is further complicated by the fact that respiratory viral infections are a trigger for asthma.
In 1969, McNicol concluded that it was clinically impossible to distinguish between wheezing bronchitis and bronchial asthma, so in practice they should be combined rather than separated, and all children with recurrent wheezing should be considered as having bronchial asthma until After the 1880s, childhood wheezing was gradually covered by the diagnosis of “bronchial asthma”, which changed the global underdiagnosis and under-treatment of asthma, which was beneficial for most older children because it reduced the use of antibiotics. However, this has not been the case in infants and young children, where the threat of bronchial asthma has been exaggerated and there has been overtreatment, with many viral-associated wheezing receiving inappropriate and ineffective anti-asthma treatments. The broadening of the diagnosis has also led to misunderstandings about the etiology of the rise in asthma incidence over the past 20 years.
III. High-risk factors for bronchial asthma
The Tuscon Children’s Research Center has created indicators to determine the risk factors for the development of asthma in infants and children with recurrent wheezing.
1. physician diagnosis of parental asthma
2. physician diagnosis of atopic dermatitis
1. doctor’s diagnosis of allergic rhinitis
2. wheezing not caused by a cold
3. eosinophilia ≥ 4%
Strict criteria included recurrent wheezing in the first 3 years of life plus another major risk factor (parental history of asthma or eczema) or 2 of the 3 minor risk factors (eosinophilia, wheezing due to non-colds and allergic rhinitis).
Less stringent indicators included any wheeze in the first 3 years of life plus the same risk factors mentioned above.
Application of these indices revealed that 59% of children with asthma symptoms at 6 to 13 years of age were positive for the less strict indices, 76% for the strict indices, and more than 95% of children with negative strict indices did not have asthma at 6 to 13 years of age. Application of these indications can correctly and reasonably predict the occurrence of asthma later.
IV. The value of hormone application in recurrent wheezing in young children
The controversy regarding the treatment of wheezing in infants and children has been longstanding, due to the complexity of the local administration modalities and the difficulty in evaluating the response to treatment. Since most have a good prognosis, the need for their treatment is also worthy of consideration. Many studies have reported that bronchodilators have no or only mild effect on relieving wheezing symptoms, probably because the main pathology of wheezing in infants and children is airway edema and mucus plug formation due to inflammation, so they do not respond to beta receptors. Inhaled hormones are the main preventive measure for bronchial asthma in older children, but their therapeutic status in infantile wheeze is unclear.
(i) Whether hormone therapy can reduce wheezing after RSV capillary bronchiolitis
Data from the UK concluded that early nebulized inhalation of budesonide for 6 weeks did not reduce the symptoms of capillary bronchitis or prevent wheezing recurrence within 6 months. A Danish study found that oral prednisone given to children < 24 months of age hospitalized for RSV infection did not affect symptoms in the acute phase, nor did it affect prognosis at 1 month and 1 year after hospital discharge. In the Netherlands, oral prednisone during the acute phase of capillary bronchitis was not found to reduce the incidence of wheezing at 5 years of age, and FOX reported that nebulized budesonide inhaled for 8 weeks after hospitalization for viral capillary bronchitis did not reduce the incidence of cough and wheezing at 12 months. In contrast, Kajosaari reported that inhaled hormones were effective in preventing wheezing after RSV capillary bronchitis, with the greatest benefit in children with atopic symptoms. A Swedish study found that inhaled hormones for 6 to 8 weeks reduced the incidence of wheezing and severe respiratory disease. Finland reported that nebulized inhaled budesonide given for 4 months reduced the incidence of recurrent wheezing, but the effect disappeared soon after termination of treatment. From the above data, it can be seen that there is insufficient evidence that hormones can reduce recurrent wheezing that occurs after RSV capillary bronchitis.
(B) Whether hormones have a preventive and curative effect on recurrent wheezing
The long-term goal of hormone therapy is to prevent airway remodeling, while the short-term goal is to control symptoms. Because bronchial asthma begins in childhood, some pediatric respiratory specialists believe that early hormone therapy can alter the course of the disease and prevent airway remodeling and irreversible airway obstruction, while others question whether and when hormone therapy should be initiated for recurrent wheezing in young children. First, there are many etiologies for wheezing in young children, most commonly viruses, which have a different pathogenesis than bronchial asthma and are less likely to develop into bronchial asthma later, and long-term hormone therapy for this group of children, especially those under 3 years of age, may result in overtreatment. Second, in children with asymptomatic bronchial asthma, impaired lung function does not necessarily indicate irreversible airway obstruction, it only suggests the presence of mild airway inflammation; furthermore, although new inhalation devices are available, it is still difficult to have sufficient drug deposition in the airways; furthermore, due to differences in study design, adoption criteria, treatment duration, and study endpoints, information about the effects of hormones on the acute and Finally, evidence-based studies have not demonstrated a benefit of inhaled hormones for virus-associated wheezing. Therefore, hormone therapy for infants and children with recurrent wheezing needs to be administered with caution.
(iii) Which children can be treated with hormone therapy
In the 2002 edition of the NHLB I guidelines for the management of bronchial asthma, experts recommend long-term control therapy for infants and children with the following characteristics:
(1) Need for medication to control symptoms more than twice a week.
(2) Two severe wheezing episodes less than 6 weeks apart.
(3) More than 3 episodes of sleep-disrupting wheezing in the past 1 year with risk factors for development of bronchial asthma such as parental asthma, atopic dermatitis, allergic rhinitis, wheezing without a cold, and elevated blood eosinophils.
In conclusion, most of the recurrent wheezing in infants and children is early temporary wheezing, mostly related to viral infections, which does not occur again after school age, and only a small percentage develops into asthma. Virus-associated wheezing, migratory capillary bronchitis, or wheezing bronchitis should be considered as the diagnosis of transient wheezing in those preschool children. There is no evidence from evidence-based medicine on the efficacy of hormones for post-capillary bronchitis wheezing and virus-associated wheezing, while hormone therapy improves symptoms and pulmonary function in children with a tendency to atopy with recurrent wheezing.
V. Advantages of Chinese medicine in the treatment of wheezing in infants and children
Chinese medicine generally applies drugs that support the righteousness and increase the immunity of children to achieve the purpose of reducing wheezing episodes, which has a better effect, but because Chinese medicine requires evidence-based treatment, it brings some uncertainty to the standardized research, and further research is needed.