Advances in the diagnosis, treatment and prevention of capillary bronchitis

1. Etiology Respiratory syncytial virus (RSV) is the most common pathogen of Mauve, accounting for more than 70% of cases.1 RSV was isolated by Chanock et al. in 1995 and belongs to the genus Pneumovirus of the family Paramyxoviridae, which is an apolar single-stranded RNA virus with an envelope and a viral diameter of about 120-20O nm. The F and G glycoproteins are the only components that form neutralizing antibodies to RSV and are the main targets of vaccine research. RSV can be divided into two subtypes, A and B. The 10 subtypes of RSV are the only ones that form neutralizing antibodies and are the main targets of vaccine research. All 10 glycoproteins of the two subtypes of RSV show some differences, but the greatest differences are found in the G glycoprotein. Both subtypes can be transmitted simultaneously in seasonal epidemics, but there are reports that RSV type A infections may cause more severe disease than type B infections. Yang J., Department of Pediatric Internal Medicine, Qilu Hospital, Shandong University, is the second leading cause of Mao Zhi after RSV, and its presence may increase the risk of severe infection by approximately 5-fold. In addition, pathogens such as parainfluenza and influenza viruses, adenovirus, mycoplasma, chlamydia, ureaplasma, and pneumocystis are less common causes of Mauve. 2. Epidemiology Initial RSV infection usually occurs under 2 years of age, with a peak at 2-8 months of age. Epidemiological surveys in the United States show that more than 80% of children with severe hairy branch are between 6 weeks and 6 months of age, and the hospitalization rate of hairy branch among children under 1 year of age in the United States is 3.42%; while the hospitalization rate of hairy branch is as high as 6.18% among American Indian and Alaska native children under 1 year of age. RSV is transmitted by droplets or infected respiratory secretions, and RSV infection is distinctly seasonal, with predictable peaks occurring in the winter months when the climate is favorable, and in the tropics during the hottest months and the rainy season. In Qatar, the peak of hospitalization for RSV Mauve is between November and February, and in the Malay Archipelago, RSV infection peaks in November, December and January each year, and the rate of RSV infection is related to the number of rainy days per month and inversely related to the average monthly temperature. These include prematurity, infection within the first 6 months of life, chronic lung disease, malnutrition, congenital heart disease, and the use of immunosuppressive drugs. Environmental risk factors include poverty, crowded housing, and passive smoking. Factors that increase the frequency of infection include young age, multiple pregnancies, atopic family history, low parental education, large family members, presence of older school-age siblings, lack of breastfeeding, day care, passive smoking, and discharge from the neonatal intensive care unit between 9 and 12 months.91 In early studies, the morbidity and mortality rate of children with cyanotic congenital heart disease hospitalized for RSV branching was as high as 37% and in children with pulmonary artery high pressure and up to 44% in children with pulmonary arterial pressure. However, due to modern intensive care techniques, the morbidity and mortality rate has now been reduced to 9%.3. Viral immunology The immune response to RSV includes humoral and cellular immunity, with humoral immunity producing antibodies that in turn include serum and secretory antibodies. In the upper respiratory tract, resistance to RSV infection is mediated by local secretory IgA antibodies, while in the lower respiratory tract it relies on serum-neutralizing antibodies. The protective effect of monthly intravenous infusion of RSV immunoglobulin (RSVãƒģIVIG) in high-risk children was further confirmed by a reduction in the incidence of RSV infection and the hospitalization associated with it. Cellular immunity also plays an important role in RSV infection and appears to be necessary to terminate the infection. RSV-specific cytotoxic T cells play a key role in the protection and pathogenesis of RSV infectious diseases. Studies have shown that RSV infection is more severe and viral shedding is prolonged in children with cellular immunodeficiency, suggesting the importance of T cells (CD4 and CDS) for disease recovery. CD4 cells are potent inducers of lung eosinophil and cytokine secretion. In children with clinical RSV hairy branch, CD4 cells were found to cause pulmonary eosinophilia and elevated serum lgE levels, and this effect was inversely proportional to the number of CDS cells in the blood. wheezing during RSV infection was then associated with increased concentrations of leukotrienes and eosinophil cationic proteins in respiratory secretions. Infected cells release proinflammatory cytokines and chemokines, including interleukin (IL)1, tumor necrosis factor I:, IL-6, and IL-8, which activate other cells and accumulate inflammatory cells, including macrophages, neutrophils, eosinophils, and T cells, into the airway wall and surrounding tissues, while whether T cells produce cytokines in favor of helper T cells (Th)1 or The Thl subpopulation secretes mainly IL-2 and tumor necrosis factor-a, while the ThZ subpopulation secretes mainly IL-4 and IL-5. Thl is usually effective against viruses, but young infants have a predisposition to ThZ dominance, and an imbalance of these factors may lead to cellular damage and worsening of lung disease. Thl is usually effective against the virus, but young infants have an innate tendency for ThZ dominance, and an imbalance of these factors may lead to cellular damage and worsen lung disease. Thus, there may be a delicate balance between the protective and pathogenic effects of T cells in RSV infection.4. Treatment Despite decades of effort, there is still no satisfactory and effective treatment for RSV hairy branch, which was further confirmed recently by Abul-Ainine et al. Earlier studies had shown that continuous ribavirin (also known as viridazole and triazolyl nucleoside) nebulizer treatment has a beneficial effect in reducing the severity of clinical symptoms and viral shedding; while other studies have shown no significant difference in the efficacy of ribavirin versus placebo in the treatment of gross branch. Therefore, based on its efficacy, cost, and safety, ribavirin nebulizer therapy should only be considered for children with severe disease or at high risk, including those with congenital heart disease, bronchopulmonary dysplasia, prematurity, and immunodeficiency, as they may destroy more severe disease. Bronchodilators, especially sympathetic stimulants, can be used to treat wheezing in the presence of hairy branches, but their efficacy is controversial. bertrand et al. looked at the efficacy and safety of nebulized inhaled epinephrine or salbutamol and found that epinephrine reduced clinical scores more rapidly than salbutamol and that both were equally safe. However, another study showed that nebulized epinephrine inhalation was no more effective than placebo or general supportive therapy. A large body of evidence suggests that the symptoms of gross RSV may have some relationship to its immunopathological mechanisms. Therefore, the administration of glucocorticoids may be an effective treatment, which was more intensively studied in the 1960s, but remains controversial. In a meta-analysis of infantile hairy streaks, systemic glucocorticoids were shown to improve clinical symptoms, and Schuh et al. administered oral dexamethasone to 70 children with hairy streaks up to 2 years of age and showed that dexamethasone administered within the first 4 hours of treatment was beneficial in reducing clinical symptoms and disease recovery. Because the acute inflammatory changes in the airways of children with Mao Zhi are similar to those of children with asthma during exacerbations, glucocorticoid nebulizer inhalation therapy for asthma has been used to treat Mao Zhi. However, most well-designed studies have failed to show a benefit of inhaled or systemic glucocorticoid application in children with Mauve. Most of the benefits of bronchodilators or glucocorticoids can be seen in children with severe disease. In a randomized trial, glucocorticosteroids appeared to be most effective in those children who required ventilator application. Recently, Martinon et al IV applied a low-density gas mixture heliox (70% helium and 30% oxygen) to treat hairy branches. The results showed that the application of heliox in children with moderate to severe hairy branch improved clinical respiratory status, significantly improved clinical scores, and reduced concomitant tachycardia and shortness of breath. This beneficial response occurred within the first hour of heliox administration and continued to be effective for the duration of treatment. In addition, the length of stay in the intensive care unit was reduced in children treated with heliox. However, these efficacies have yet to be confirmed in long-term prospective studies. Prophylactic treatment is also very important, especially in small infants at high risk. There are two available approaches, RsV.IVIG, and palivizulllab. RSv I IVIG is a highly potent purified immunoglobulin, and once monthly intravenous infusions reduce hospitalization rates by 41% in gross and significantly reduce the severity of symptoms in children at high risk of RSV infection. palivizumab (Synagis) is a human-derived monoclonal antibody that exhibits neutralizing activity directly against RSVF protein. With monthly intramuscular injections of 15 mg/kg, palivzumal reduced RSV-related hospitalizations by approximately 55%. No serious adverse reactions have been reported from the application of palivizumab in clinical trials. Both prophylactic methods are safe and effective, but they are expensive and therefore restricted to high-risk children, and both have not been evaluated in children with congenital heart disease and immunodeficiency. In addition, management of Mauve includes supportive therapy such as intravenous rehydration, inhalation of humidified oxygen, reduction of respiratory secretions and maintenance of airway patency, and, if necessary, tracheal intubation and mechanical ventilation.5. Prevention and vaccine research The development of a formaldehyde inactivated RSV vaccine in the 1960s initially seemed likely to be successful, with more than 90% of immunized children producing an antibody response. However, when the natural virus was re-activated, more severe disease could occur in these children and lead to the death of individual children. Application of animal models to study adverse reactions to inactivated formaldehyde vaccine has revealed several causes of its abnormal pulmonary pathology: first, failure to develop local secretory lgA antibodies when the vaccine is administered parenterally through the gastrointestinal tract, and susceptibility of the respiratory tract to natural RSV infection after having used the vaccine; second, dysregulation of the systemic immunoglobulin response and formation of low levels of protective antibodies; and third, dysregulation of the cell-mediated immune response. This dysregulation results in altered secretion of IL and lymphokines, leading to destruction of the fine bronchi and alveoli at the site of RSV replication. The development of a live attenuated RSV vaccine is one strategy to prevent RSV infection. Several different approaches have been tried, including the manufacture of cold-passage (cP) or temperature-sensitive (ts) mutant RSV strains. These vaccines are derived from cPts RSV strains and are produced by a chemical mutagenesis process that renders them more stable. These vaccine candidates have been shown to protect chimpanzees against wild strains of RSV, and some of them have also been evaluated by intranasal administration in infants over 6 months of age, where the vaccine strains were found to be stable and no exacerbation of disease by the vaccine was observed during the peak season of RSV infection. Other advances in vaccine research include the development of protein subunit-based vaccine solids, and the RSVF and G glycoproteins, which induce protective neutralizing antibodies, are the main components of these vaccines. A new RSV vaccine containing subunits of F and G glycoproteins or purified F glycoprotein subunits has been developed and tested. the F and G vaccine candidates induce low levels of neutralizing antibodies and provide weak protection in primates when reactivated with wild strains of RSV. Higher concentrations of secretory and serum antibodies were found after intranasal administration with the addition of non-toxic cholera sea cucumber toxin as an adjuvant. Immunization with an F-glycoprotein vaccine candidate with this adjuvant after reexcitation with a wild strain of RSV in rodents has shown protection against the lower respiratory tract. An RSVF subunit vaccine adsorbed to alum has also been evaluated in children over 1 year of age with lung disease (e.g., pulmonary cystic fibrosis), and although no protection against RSV gross was observed, a reduction in the mean number of lower respiratory tract diseases was found in those who had used the vaccine. Another oral vaccine with recombinant RSVG glycoprotein has been developed, which is produced from Salmonella spp. cells injected with a G glycoprotein-encoding plasmid. Other viral vectors such as cowpox, baculovirus, adenovirus and adjuvants (e.g. cholera toxin B and immunostimulatory complexes) are also being investigated with the hope that subunit vaccines will be observed to enhance the immune response and reduce the possible associated adverse effects. Other RSV prophylactic strategies include immunization of pregnant women in the second trimester of pregnancy, which aims to increase the level of antibodies in the mother and subsequently pass them on to the infant IV. This approach is not beneficial in preterm infants born at less than 32 weeks because they do not yet acquire sufficient amounts of passively transmitted maternal antibodies. This strategy requires further study, particularly with regard to the assessment of the potential risk of maternal vaccination and the ability to achieve protective levels in the infant.