Chinese and western medicine research progress in child adenoviral pneumonia

Yue Ma, Shan-Yun Zhang, Han Kong, Juan-Juan Diao

1.Shandong University of Traditional Chinese Medicine, Jinan 250014, China

2.Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250011, China

Keywords:Adenoviral pneumonia Chinese and western medicine treatment Syndrome differentiation and treatment Research progress

ABSTRACT Adenoviral pneumonia is one of the more serious types of community-acquired pneumonia in children. It easily develops into severe pneumonia with many extrapulmonary complications and a high mortality rate. However, there is still no effective treatment for adenovirus. Therapeutic drugs are conducive to clinical treatment. Traditional Chinese medicine often achieves satisfactory results through staged syndrome differentiation. Currently, heat, sputum, stasis, and poison are considered to be the main pathological products. Fever, phlegm, and stasis are present in its development. Analyze the progress of traditional Chinese and western medicine in children's adenoviral pneumonia, and have a clearer understanding of the law of syndrome differentiation and its prescription medication, providing ideas for clinical treatment of adenoviral pneumonia.

Adenoviral pneumonia (AVP) is pneumonia caused by adenovirus infection. According to statistics, 4% to 10% of childhood pneumonia is caused by adenovirus infection [1],It is one of the most severe types of community acquired pneumonia in children [2].Frequently occurring in infants and toddlers 6 months to 2 years old, with persistent high fever, cough, shortness of breath, wheezing, and dyspnea as the main clinical manifestations. In the acute phase, the most common complications are respiratory failure, myocarditis and liver function damage with high mortality [3].Adenovirus mainly invades the respiratory mucosa, bronchial wall and alveolar epithelial cells, causing tissue damage and causing bronchial obstruction. It can also reach the liver, spleen, kidney, and central nervous system through the blood, causing other system damage. Severe conditions can also affect electrolyte acidbase balance, Liver and kidney function, coagulation function, etc.Yukihiko K et al. [3,4]found that compared with other respiratory virus infected pneumonia, the fever of adenovirus pneumonia lasted longer, and the significantly increased levels of white blood cell count, CRP, IL-6 and TNF-α, mainly neutrophils.At present, there is a shortage of antiviral drugs with high specificity and small toxic and side effects for adenovirus.Modern medicine is mainly based on comprehensive treatment, In recent years, the research on AVP in the field of traditional Chinese medicine has deepened.According to the theory of traditional Chinese medicine, the application of traditional Chinese medicine and other treatment methods, achieved a certain effect.This article summarizes the research progress of adenoviral pneumonia in traditional Chinese and western medicine in recent years as follows.

1. Source of disease name

Although there is no record of the disease name of "adenovirus pneumonia" in ancient Chinese literature, according to the characteristics of the disease, they belong to the categories of "heat disease", "wind-warm syndrome", and "epidemic febrile disease".[5]According to its clinical manifestations, it is related to the names of traditional Chinese medicine, such as "asthmatic wheezing" and "pneumonia asthma" [6,7]Many of the original sentences in Chinese medicine books such as Huangdi Neijing describe the symptoms of children's feeling of exogenous pathogenic factors, similar to the symptoms of heart failure in viral pneumonia.

2. Etiology and pathogenesis

The occurrence of adenovirus pneumonia is caused by the external responsibility for the six climatic evils or pestillence[8],the internal cause of the child's delicate lung, wei external not solid.The general pathogenesis was pulmonary qi stagnation, and the pathological factors involved heat, phlegm, toxin, blood stasis, etc.Combined with the physiological and pathological characteristics of children and the different degree and course of disease,Clinically, there are differences in superficies and interior , cold and heat, deficiency and excess, Yin and Yang, there are individual differences in simultaneous superficies and interior syndromes, disease of one channel involving another channel , deficiency complicated with excess and other syndromes.Pu fuzhou [9]found that attacked by six climate pathogenic factors, wind blockage, cold blockage and heat blockage could be the cause of adenovirus pneumonia.Dong tingyao [10] believed that in the treatment of adenovirus pneumonia, the pathogenesis of warm-hot syndrome should be mastered.Wenbing Tiaobian,the syndrome of warm-hot is described, the evil attacked lung and stomach, or spreads the heart nutrient, or reversed transmission to pericardium, such as according to the direction of nutrient and defensive or qi, blood tier transmission change, serious can also appear dynamic wind, blood consumption change. Wang shouchuan[11]put forward the academic thought of "clearing lung and detoxification" treatment, and believed that children's viral pneumonia should be treated from heat, phlegm and blood stasis.

3. Syndrome differentiation and treatment

3.1 Wind and cold closed lung syndrome

This syndrome is mostly seen in the early stage of the disease, mainly caused by wind and cold attack of the lung.Syndrome shows fever light, aversion to cold heavy, little or no sweat, cough, red tongue, thin white moss, pulse floating tight.Wang Xia [12] the 68 cases of children with adenovirus, were randomly divided into control group with conventional western medicine treatment, the treatment group according to syndrome differentiation of traditional Chinese medicine for wind-cold attacking lung type, mahaung,suye,fangfeng for relieving exterior syndrome by diaphoresis, qianhu,jiegeng for free activity of lung qi,baijeizi,suzi for drying dampness and resolving phlegm,chantui,gegen for Auxiliary defervescence, Results the time of heat retreat, lung signs disappeared, and the X-ray lung shadow disappear time as shorter than the control group, the total effective rate was 97.7%.Pu fuzhou

[13] put forward the treatment principle of dispersing cold to promote lung phlegm in the patients with adenovirus pneumonia caused by cold attack of the lung,with the traditional Chinese medicine prescription xingsu and congchitang.just as wu jutong said: "on the treatment of upper energizer such as feather, not light do not lift", is means medicine smell must be thin and light, to achieve the power of relief lung qi for pediatric lung diseases drugs.

3.2 Wind and heat closes lung syndrome

This syndrome is mostly seen in the early stage of the disease, mainly caused by wind and heat attack of the lung.Clinical manifestations: fever, fear of wind, shortness of breath, cough, large amount of sputum, yellow color, pharyngeal red, tongue red moss white or yellow, number of floating pulse.Jiang yuren [14]believed that the wind and heat closes lung syndrome was mostly caused by Healthy-Qi abundant, evil is little. The main syndromes were lung gas loss regulation, sputum obstruction lung .thirty-one children with adenovirus with wind-heat syndrome were treated with maxingshigan and yinqiao prescription, and the cure rate was 89%.Pu fuzhou

[15] has a very good therapeutic effect with sangxing prescription.Tan yong [12] treated sixteen children with wind-heat closed lung adenovirus pneumonia with self-designed prescription, using mahuang and shigao for clear away lung-heat,sangye for relieving exterior syndrome by diaphoresis,yuxingcao,huangqin for method of expelling phlegm,baibu,zhebeimu for liminating phlegm and resolving turbidity.After a certain course of treatment, the total effective rate was 97.7%.

3.3 Accumulation of phlegm-heat syndrome

This syndrome is mostly seen in the middle stage of pneumonia or severe children.The invasion of exogenous pathogens affects the function of lung and spleen, body fluid distribution metabolism is abnormal, stuck in the body, coagulation and sputum.Clinical manifestation is fever, cough, phlegm much, dyspnea, phlegm thick color yellow, thirsty, tongue red moss yellow greasy, pulse slippery number.Principle of treatment is removing heat-phlegm. Dong tingyao[16]created xiongshe powder, which was composed of deerhorn glue and Bear bile withformula for clearing nutrient level and cooling blood effects, and was ground for oral administration, achieving satisfactory clinical results.He xiangguang[12]treated 18 children with adenovirus with accumulation of phlegm-heat syndrome with self-designed prescription,and treated them with shig ao,tinglizi,sangbaipi,xingren,huangqin,yuxingcao,zhebeimu,gancao, with a total effective rate of 97.7%.

3.4 Dampness-heat closes lung syndrome

This syndrome is mostly seen in the middle stage of pneumonia.Evil heat impinges the lung, the function of delivering body fluid decreases, and produces humidity, dampness-heat combine with evil spirits, hot steam and wet movement,heat makes the humidity move.In recent years, the rhythm of life and dietary structure have changed, Excessive consumption of sweet, fatty food, too little exercise, coupled with the physiological characteristics of the spleen is often insufficient, the endogenous wet and pathogenic conditions are increasingly common.Clinical manifestations include fever, heavy cough, phlegm, thick, white or yellow, drowsy limbs, abdominal distension, loss of appetite, yellow and greasy tongue coating, and smooth pulse.Treatment should formula for harmonizing the stomach and drying.Ye Yonghua[17] thinks "dampness-heat type" is mainly due to the dampness-heat cross, failure of lung qi in dispersion.Wu jutong's 《Wenbing Tiaobian》says,sanrentang can treat adenovirus children, the role is the regulating qi activity, clean dampness-heat (xingren,baikouren,mahuang,fuling,yiyiren,baizhu,houpu,banxia,chenpi,huangqin,ganjiang,gancao) take orally. 7 days after the recovery.Bi qianyu et al. [18,19]found in the experimental study on rats with dampness-heat viral pneumonia that “sanrentang” and “ganluxiaodudan” could inhibit the mRNA expression of viral nucleic acid through multi-target intervention, providing a modern pharmacological basis for the clinical treatment of damp heat viral pneumonia.“Clearing dampness-heat method ”commonly used representative formula for “sanrentang” and “ganluxiaodudan” , The former is more important than the regulating qi activity, calming heart for wet, is suitable for the early stage of disease, dampness than heat, The latter is the opposite, disinfection from the “Shire Jingwei”.

3.5 Phlegm stasis closed lung syndrome

Common in the polar stage of pneumonia,The lung governs qi, controlls breathing, visible evil affects the movement of qi and blood, children often shows pale face, lip nail purple, purple dark tongue, such as signs of blood stasis.In Jingui YaolueIn , it is said that "where heat passes, blood will coagulate."Li bing-nan [20] believed that the invasion of external pathogens could easily cause the heat of cremation and the take away liquid into phlegm, resulting in the stagnation of lung qi and blood stasis. Therefore, there are signs of blood stasis in pneumonia, so it is necessary to use and reuse blood-activating products early.Yan tianyu [21] discussed the basis of distinguishing "blood stasis syndrome" of adenovirus pneumonia in children and the mechanism of treating adenovirus pneumonia by activating blood circulation and removing blood stasis. A total of 93 cases of adenovirus pneumonia combined with DIC were collected and treated with traditional Chinese medicine huayu decoction.(danggui 9g,chishao 9g,chuanxiong 9g,jixueteng 12g,shuizhi 9g,danpi 6g,huangqi 15g), the total effective rate was 77.4%, lung microvascular system one of the most abundant organs, is viral infection of the lung microvascular will be affected by certain influence, through animal experiments found that kind of Chinese traditional medicine for activating blood circulation can reduce leakage and hemorrhage, alveolar edema, cellulose to relieve or prevent lung microvascular thrombosis, avoid the occurrence and development of DIC.Li yanning [22] believed that in the treatment of viral pneumonia, the early use of drugs to promote blood circulation and remove blood stasis is conducive to the dissipation of inflammation, the recovery of the disease and the prevention of severe disease and syndrome.

3.6 Syndrome of heat-toxicity blocking lung

More common in severe pneumonia,too much heat not only dissipates body fluid, it can also seduce the blood and cause blood stasis[23].The main clinical manifestations are persistent high fever, severe cough, wheezing, dry nasal cavity, red face and red lips, irritability and thirst, constipation, red tongue and yellow tongue coating, and pulse number.Liu li[24]believed that the heat-toxicity was blazing, they tend to burn fluid like fire,should be treated to clear the heat to detoxify, blood circulation to remove blood stasis, maxingshigantang combined with sanhuangshigaotang or qingwenbaiduyin, qingyingtang to reduce the clinical efficacy is good.Yao jingying [25,26] proposed that the heart governs the blood and (blood ) vessels, lung governs qi. and flow of qi and blood. The heat-toxicity affects the lung and further affects the function of the heart and blood, which can gradually develop into the decay syndrome of qi deficiency of heart and lung .

3.7 Other type

In the recovery period of the disease, the heat-toxicity of the evil consumption of body fluid,deficiency of lung yin , dry cough without phlegm, red tongue less moss, pulse fine number of deficiency of lung fire yin syndrome.In theory of five elements, lung and spleen for the relationship between children and mother, physiology and pathology affect each other,See cough feebleness, fatigue, no appetite, deficiency of lung and spleen yin symptoms.In later stages,adenovirus pneumonia can appear serious change, Phlegm, heat, blood stasis affect each other, affect the heart,form stagnant blockade of heart blood syndrome type.In addition, deficiency of heart yang syndrome and Jue Yin syndrome.

3.8 Syndrome differentiation of weifen

Some clinical syndromes of adenovirus pneumonia are often treated by differentiation of weiqi and blood.Wei jun [27] divided 60 children with adenovirus into four types according to the syndrome differentiation of weiqi-yingxue: excessive heat at qi phase,rules of treatment is “formula for clearing nutrient level and cooling,method of relieving cough”,the treatment of maxingshigantang and sanhaungjiedutang was selected.Heat into the ying phase, treatment to clear the ying phsae of heat-toxicity, the prescription of qingyingtang;When the disease reached jue Yin, should be treated with cooling blood for calming endogenous wind,the prescription of lingjiaogoutengtang;Toxic heat in sheng, qi stagnation and blood stasis, appropriate blood circulation.In the qi stagnation-blood stasis, treatment to warming uterus for dispelling cold and formula for clearing nutrient level and cooling, the prescription of taohongsiwutang, The clinical effect is very good.

4. Stage treatment

According to the basic rule of pediatric adenovirus pneumonia, the course of disease was divided into three stages [28].At the beginning of the excess type,fever, cough, thirst, red face, no sweat, etc.In the middle period, deficiency complicated with excess,fever slightly sweat, slightly wheeze, chest full, thin or dry stool;At the end of the period, there are many symptoms such as blood deficiency and Yin injury, body heat without sweat, cough, asthma, thirst and sweat.Pu fuzhou[29] put forward the "seven-day theory" of adenovirus pneumonia. Seven days ago, the treatment method was mainly to attack evil.After seven days, asthenia complicated with sthenia,most of its methods of governance are to support the good and drive away evil, attack and remedy both.In the late stage of pneumonia, more injuries to the qi Yin, the treatment of yiqishengjin-based.Observe traditional adenovirus pneumonia hospitalized children in shandong province in recent years,It was observed that at the early stage, wind and cold closed lung syndrome,wind and heat closes lung syndrome and accumulation of phlegm-heat syndrome etc.In the later period, the evolution of pathogenesis and syndromes such as lung-spleen deficiency or lung-heat syndrome of yin-deficiency were frequently observed.

5. Chinese patent medicine injection

Shaw fxiqing[30] take the control group of 50 cases of children with adenovirus to conventional symptomatic treatment, 50 cases in observation group based on the xiyanping injection treatment, after 3 to 5 days (94.0%), total effective observation group was obviously higher than that of control group (76.0%), studies have shown that [31], xiyanping injection is made for herba extract of andrographis has inhibitory effect to virus, inflammation effusion.Wei Hong[32]take 256 cases were randomly divided into 130 cases of traditional Chinese medicine group and 126 cases of control group, the traditional Chinese medicine group to yujin injection static drop, at the same time of oral Chinese herbs on our own(mahuang,shigao,zhimu, huangqin, shegan, dilong, banxia,zisuzi, jiegeng, gancao) and control group in the conventional western medicine treatment,after a certain period of treatment, Chinese medicine group of cough and days of fever and chest radiograph returned to normal as shorter than the control group, the curative effect is significant.Yujin injection is mainly composed of herba houttuyniae and honeysuckle.Pharmacological studies have clarified that the combination of two drugs has a variety of antiviral effects

[33].

6. Other traditional Chinese medicine treatment

ShiJingLi etc.[34]taked 30 cases of adenovirus pneumonia of children, to the Chinese medicine atomization inhalation mixtu re,jinyinhua,yuxingcao,huangqin,guanzhong,beimu,kuandong hua,gancao,and the control group with dexamethasone aerosol inhalation, besides the two groups were conventional symptomatic treatment, treatment group total effective rate 96.7% higher than the control group effectiveness 90.0%, respiratory drug delivery is a new effective way to treatment of pediatric pneumonia, inhaled medications were given is an oral drug concentration is high, can play an importent role of treatment[35] .Some monomers and active components of traditional Chinese medicine also have antiadenovirus effects. Cytopathic effect method method were used to study the anti-adenovirus effects of traditional Chinese medicine monomers such as shikonin, astragaloside IV[36].Shuanghuanglia n,kangbingdu,etc,other proprietary Chinese medicine, according to the treatment of TCM syndrome differentiation thought[37], has been widely used in clinical treatment and has a satisfactory effect.In addition, traditional Chinese medicine therapies such as rectal administration, acupuncture and cupping can play a positive role in shortening the course of disease in improving the clinical symptoms of children's viral pneumonia [38,41].

7. Western medicine for antiviral treatment

Human adenovirus is a double-stranded DNA virus without an envelope. Since there is no specific drug for adenovirus at present, literature reading and clinical research have found that the virus inhibitors commonly used to treat children's viral pneumonia include aciclovir, ganciclovir, interferon, ribavirin, abidor, etc.Interferon [42] mainly interferes with and destroys the synthesis of viral proteins, and is applied in the infection of cytomegalocyte, influenza and herpes zoster virus. In recent years, it has been found in clinical studies that interferon atomization inhalation in the treatment of viral pneumonia in children can improve the clinical treatment effect and shorten the treatment cycle.Liu Junfeng[43] taked the 120 cases of children with adenovirus pneumonia were randomly divided into control group and treatment group of 60 cases, join vidarabine static in foundation treatment in the control group, treatment group was added with interferon atomization inhalation, the results showed that the treatment group was normal, cough and alleviate breath suppress a shorter time than the control group, the difference statistically significant(P＜ 0.05).Ganciclovir is a synthetic type of spectrum nucleoside antiviral drug, which has a certain strong antiviral effect, has an active therapeutic effect on EB, herpes zoster, herpes simplex and cytomegalovirus infection, and has an inhibitory effect on adenovirus.Lu liong[44] observed the efficacy of ganciclovir in the treatment of adenovirus pneumonia. Seventy-eight children were randomly divided into the treatment group with 42 cases of ganciclovir and the control group with 36 cases of ribavirin. Results the total effective rate of the treatment group (80.95%) was significantly higher than that of the control group (22.22%), and the difference was statistically significant (P＜0.01).Ribavirin is a new nucleoside broad-spectrum antiviral drug, which can block the synthesis of viral nucleic acid and inhibit the replication and transmission of the virus. It has been clinically confirmed that it is the most sensitive to herpes virus and respiratory syncytial virus, and it also has definite effects on adenovirus and parainfluenza virus[45].Acyclovir is a nucleoside class efficient broad-spectrum antiviral drugs, the herpes virus DNA polymerase has a strong inhibitory effect, feng-ying tang[46]taked 60 cases of adenovirus pneumonia patients were randomly divided into control group 29 cases, 31 cases of observation group, respectively with ribavirin, acyclovir intravenous drip , the results observed group total effective rate 97.5% higher than the control group total effective rate was 60%. Cidofovir[47] competitive inhibition virus DNA polymerase and prevent virus DNA synthesis, is a broad spectrum of DNA virus drugs, clinical used in the treatment of low immune function and adenovirus infection of critical patients, Ko JH [48] take the severe symptoms of adenovirus pneumonia patients with cidofovir, found that early use cidofovir can lower the risk of respiratory tract infection and the incidence of respiratory failure, but because of the lack of a large number of clinical trials and high costs,As well as potential side effects (kidney damage, mutagenicity and reproductive toxicity), children should be selected with extreme caution.

8. Summary and prospect:

Early detection and intervention is the key to improve prognosis and reduce death.Comprehensive analysis of adenovirus pneumonia recommend early can use Ganciclovir, interferon.there interferon antiviral medications, such as for low immunity, children with severe suggest appropriate use cidofovir, but due to the current research of adenovirus pneumonia in children is still in the stage of clinical observation, the lack of a large number of clinical trial data and modern experimental methods of detection and report, without the long-term curative effect and side effects evaluation, therefore, when applying these antiviral drugs still need to observe the adverse reaction and the effect is significant.By virtue of its unique syndrome differentiation system, TCM has achieved remarkable results with its advantages of multiple approaches, multiple targets and low side effects.According to the diagnosis and treatment plan and literature research made by the national health and physical hygiene commission and the national administration of traditional Chinese medicine for adenovirus pneumonia, adenovirus pneumonia is divided into four stages and eight types.In the early stage, sanaotang was used for wind and cold closed lung syndrome and wind and heat closed lung syndrome use yinqiaosan and maxingshigantang.In the middle stage,dampness-heat closes lung syndrome use ganluxiaodudan and and sanrentang,wuhutangtinglidazaoxiefeitang was used for accumulation of phlegm-heat syndrome.Hanglianjiedutang and maxingshigantang were selected as the prescription of severe stage syndrome of heat-toxicity blocking lung.On the basis of clearing heat,phlegm stasis closed lung syndrome,activating qi and eliminating stasis drugs were added such as danshen,taoren,chuanxiong,honghua,chishao etc.In the later period, it is more common to select renshenwuweizitang for deficiency of lung-spleen qi syndrome, and to select shashenmaidongtang for Yin deficiency and lung heat syndrome.Severe adenovirus pneumonia is prone to severe disease,Yang deficiency of heart can be given shenfulongmujiunitang,In jue Yin disease can be selected lingjiaotoutengtang.In the whole pathological evolution process of adenovirus pneumonia, heat, toxin, phlegm, blood stasis are interrelated, especially to pay attention to the situation of blood stasis, four periods should be appropriate use of drugs to promote blood circulation and remove blood stasis, prevention and treatment of severe disease.Integrated traditional Chinese and western medicine therapy is a new trend in the treatment of adenovirus pneumonia. Although there is no unified syndrome differentiation and treatment, it will gradually become a hot topic in this field.It still needs the unremitting efforts of clinical and scientific researchers to explore the advantages of integrated traditional Chinese and western medicine and give full play to the characteristics of traditional Chinese medicine, and actively seek more diversified, feasible and effective treatment methods.