Status asthmaticus

Introduction to asthma status Asthma persistence refers to a severe asthma attack that is not effective with conventional treatment and lasts for more than 12 hours. Asthma persistence is not an independent type of asthma, but its physiology changes are more severe, and there is a risk of death if its severity is underestimated or treatment is inappropriate. Autopsy data from death from asthma showed that the most significant abnormality was excessive lung expansion, which was caused by air retention due to diffuse airway obstruction. There is a wide range of mucus plugs in the airway. This mucus plug consists of mucus, exfoliated epithelial cells and inflammatory cells, sometimes forming a small bronchi and its branches. Airway wall thickening, a large number of eosinophil infiltration, smooth muscle and submucosal gland hypertrophy and hyperplasia. The main manifestation of asthma persistence is shortness of breath. Most patients can only have single-spoken words, tachycardia, hyperinflation of the lungs, wheezing, assisted respiratory muscle contraction, odd veins and sweating. Diagnosis of asthma persistence requires exclusion of cardiogenic asthma. , COPD, upper airway obstruction or foreign body and pulmonary embolism, the most objective indicators to determine the degree of airway obstruction are: PEFR and / or FEV1. The clinical indication that asthma is critical is that the condition is still worse under adequate medical treatment; dyspnea affects sleep and speech; assisted respiratory muscle contraction; conscious change; pneumothorax or mediastinal emphysema; pulse rate >120 beats/min; respiratory rate > 30 times/min; odd pulse>2.4 kPa (18 mmHg); FEV1>0.5L; FVC<1L; PEFR<120L/min; PO2<8.66kPa (65mmHg); PCO2 is higher than normal. basic knowledge Proportion of disease: secondary to asthma, accounting for 4%-7% of asthma incidence Susceptible people: no specific population Mode of infection: non-infectious Complications: emphysema, pulmonary heart disease

Causes of persistent asthma

Genetic factors (30%):

Asthma is a disease with complex traits and multiple genetic predisposition. It is characterized by 1 incompleteness, 2 genetic heterogeneity, 3 genetic inheritance, and 4 synergistic effects. These lead to a correlation between the genetic linkages found in a population.

In a different group, the Asthmatic Genetics Collaborative Research Group (CSGA) studied 140 families in 3 races, using 360 autosomal short tandem repeat polymorphism genetic markers for genome-wide scanning. The asthma candidate genes were roughly mapped to 5p15; 5q23-31; 6p21-23; 11q13; 12q14-24.2; 13q21.3; 14q11.2-13; 17p11.1q11.2; 19q13.4; 21q21 and 2q33, these genetics The genetic susceptibility genes of asthma that may be contained in the identified chromosomal regions are roughly classified into three categories: 1 HLA class II molecular genetic polymorphisms that determine the susceptibility to allergic diseases (eg, 6p21-23); 2T cell receptors (TcR) Highly diverse and specific IgE (eg 14q11.2); 3 cytokine genes and drug-related genes (eg 11q13, 5q31-33) that define IgE regulation and development of characteristic airway inflammation in asthma, within the 5q31-33 region Contains cytokine clusters (IL-3, IL-4, IL-9, IL-13, GM-CSF), 2 adrenergic receptors, lymphocyte glucocorticoid receptor (GRL), leukotriene C4 synthesis Enzyme (LTC4S) and other candidate genes associated with asthma, these genes regulate IgE and inflammation of asthma Biodevelopment is important, so 5q31-33 is also known as the "cytokine gene cluster."

None of the above identified chromosomal regions showed evidence of linkage to more than one ethnic group, indicating that specific asthma susceptibility genes are only of relative importance, and that environmental factors or regulatory genes are involved in disease expression for different races. There are differences, and it suggests that asthma and atopy have different molecular genetic basis. These genetic chromosomal regions are large, with an average of >20Mb of DNA and thousands of genes, and many results cannot be repeated due to the limitation of specimen size. It can be seen that there is still a lot of work to be done to find and identify asthma-related genes.

Allergen (20%):

The most important stimulator of asthma may be the inhalation of allergens.

(1) Indoor allergens: The eaves are the most common and most harmful indoor allergens. They are important pathogenic factors for asthma worldwide. There are four common types: house dust mites, dust mites, and dust mites. And more than 90% of the mites are found in house dust. House dust mites are the most important aphids in the continuous humid climate. The main antigens are DerpI and DerpII. The main components are cysteine protease or tyrosine protease. For example, cats, dogs, and birds release allergens in their fur, saliva, urine, and feces. Cats are the most important sensitizers in these animals. Their main allergens are feldl, which has cat hair. And sebum secretions, which are the main risk factors for acute asthma attacks, which are common indoor allergens in Asian countries; common cockroaches associated with asthma are American cockroaches, German cockroaches, Oriental cockroaches and black-chested cockroaches Among them, black-breasted cockroaches are most common in China. Fungi are also one of the allergens present in indoor air, especially in dark, humid and poorly ventilated areas, commonly known as Penicillium, Aspergillus, and Alternaria. ,Minute Phytophthora and Candida, among which Alternaria has been identified as a risk factor for asthma, a common outdoor allergen: pollen and grass powder are the most common outdoor allergens that cause asthma attacks. Woody plants (tree pollen) often cause spring asthma, while grasses and alfalfa pollen of grasses often cause autumn asthma. The eastern part of China is mainly ragweed pollen; the northern part is mainly wormwood.

(2) Occupational allergens: common allergens that can cause occupational asthma, grain, wood, feed, tea, coffee beans, silkworms, pigeons, mushrooms, antibiotics (penicillin, cephalosporin), Cyanate, phthalic acid, rosin, reactive dyes, persulfates, ethylenediamine, etc.

(3) Drugs and food additives: Aspirin and some non-corticosteroids are the main allergens of asthma caused by drugs. Food additives such as salicylate, preservatives and stains can also cause acute asthma attacks, royal jelly. Oral liquid is widely used as a health care product in countries and regions of China and Southeast Asia. It has been confirmed that royal jelly can cause acute asthma attacks in some patients, which is an allergic reaction mediated by IgE.

Promoting factors (15%):

(1) Air pollution: Air pollution (SO2, NOx) can cause bronchoconstriction, transient airway reactivity is increased and can enhance the response to allergens.

(2) Smoking: Cigarette smoke (including passive smoking) is the main source of indoor triggering factors, and is an important asthma triggering factor, especially for asthmatic children whose parents smoke, often causing asthma attacks due to smoking.

(3) Respiratory virus infection: Respiratory virus infection is closely related to asthma attack. Infant bronchial virus infection is particularly concerned as the starting cause of asthma. Common respiratory viruses include respiratory syncytial virus (RSV), adenovirus, and rhinovirus. Influenza virus, parainfluenza virus, coronavirus, and certain enteroviruses. The viruses associated with adult asthma are mainly rhinovirus and influenza virus; respiratory syncytial virus, parainfluenza virus, adenovirus and rhinovirus are associated with childhood asthma. The seizures are closely related. The syncytial virus is the main pathogen in the first year after birth, accounting for 44% of infectious asthma under 2 years old, and more than 10% of it is associated with infection in large children's asthma. It has been reported that after RSV infection Nearly 100% of epithelial cells in patients with asthma or bronchiolitis have IgE attachment, and 42% of children hospitalized for acute RSV infection develop asthma after 10 years.

(4) Perinatal fetal environment: T lymphocytes can be produced in the fetal thymus at 9 weeks of gestation. B-lymphocytes have been produced in various organs of the fetus from the 19th to 20th week, due to the main auxiliary in the placenta during pregnancy. Type II T cell (Th2) cytokines, so in the microenvironment of the lung, the Th2 response is dominant. If the mother has a specific constitution, it is exposed to a large number of allergens during pregnancy (such as milk in milk). Globulin, egg protein in eggs or Derp I in aphids, or repeated infection by respiratory viruses, especially syncytial viruses, may aggravate their Th2-regulated allergic reactions and increase the likelihood of postnatal allergies and asthma .

In addition, the intake of polyunsaturated fatty acids in the third trimester of pregnancy will affect the production of prostaglandin E, which may be related to the allergic reaction of Th2 cell regulation. The mother's smoking during pregnancy will definitely affect the fetal lung function and future asthma. The susceptibility to the sound.

(5) Others: strenuous exercise, climate change and a variety of non-specific stimuli such as: inhalation of cold air, distilled water droplets, etc. In addition, mental factors can also induce asthma.

Pathogenesis

There are many reasons for the formation of asthma persistent state, and the mechanism of occurrence is complicated. The reason why asthma patients develop severe asthma is often multi-faceted. As a clinician, in the rescue of patients with severe asthma, it should be clearly recognized that if the disease is to be effectively controlled In addition to timely diagnosis and treatment of severe asthma, it is very important to find out the cause of each patient's development of severe asthma and to eliminate it. The following are the most obvious causes:

1. Allergen or other asthmatic factors persist

Asthma is caused by bronchospasm, rapid airway reaction and delayed phase reaction after specific stimulation, causing bronchospasm, airway inflammation and airway hyperresponsiveness, resulting in airway stenosis, if the patient continues to inhale or contact with allergens or Other anti-asthmatic factors (including respiratory infections) can cause persistent sputum bronchial smooth muscle and progressive aggravation of airway inflammation, epithelial cell exfoliation and damage to the mucosa, mucosal congestion and edema, mucus secretion and even formation of mucus plugs, plus airway Extremely smooth muscles can severely block the respiratory tract, causing asthma to persist and difficult to relieve.

2. Improper application of 2 receptor agonists and/or inadequate anti-infective treatment

It has been confirmed that asthma is an airway inflammatory disease, so anti-inflammatory drugs have been recommended as the first line of drugs for the treatment of asthma. However, many asthma patients have long-term bronchodilators as the main treatment, anti-infective treatment. Inadequate or inappropriate use of anti-infective treatment drugs, resulting in airway allergic inflammation is not effectively controlled, airway inflammation is becoming more serious, airway hyperresponsiveness is worsening, asthma is worsening, and long-term blind use of 2 agonists The 2 receptor can be down-regulated, causing it to desensitize. In this case, sudden withdrawal of the drug can cause a significant increase in airway responsiveness, thereby inducing critical asthma.

3. Dehydration, electrolyte imbalance and acidosis

During asthma attacks, patients sweat more and open mouth breathing to increase the loss of water in the respiratory tract; when oxygen therapy is used, insufficient warming and humidification; aminophylline and other strong heart, diuretics make urine volume relatively increase; plus patients breathing difficulties, drinking water Less factors, therefore, patients with asthma attacks often have different degrees of dehydration, resulting in tissue dehydration, sputum thick, forming a mucus plug that can not cough up, extensively block small and medium airways, aggravating breathing difficulties, leading to ventilatory dysfunction , the formation of hypoxemia and hypercapnia, at the same time, due to lack of oxygen, less food, increased acid metabolites in the body, can be combined with metabolic acidosis, in the case of acidosis, airway response to many asthma drugs Lower, further aggravating asthma.

4. Suddenly stop the hormone, causing "bounce phenomenon"

Some patients have long-term repeated application of glucocorticoids due to ineffectiveness of general antiasthmatic drugs or improper treatment by doctors, which makes the body dependent or tolerant. For some reasons such as lack of medicine, surgery, pregnancy, gastrointestinal bleeding, diabetes Or sudden treatment of glucocorticoids caused by treatment errors can make asthma uncontrollable and exacerbated.

5. Emotions are too tight

The patient's concerns and fears on the one hand can increase bronchospasm and dyspnea through cortical and autonomic reflexes; on the other hand, staying up all night, the patient is physically weak; in addition, the mental emotions of clinicians and family members can also affect patients and promote asthma. The condition worsened further.

6. Influence of physical and chemical factors and factors

Some reports have found that some physical and chemical factors such as temperature, humidity, air pressure, air ions, etc., can have different degrees of effects on some asthma patients, but the mechanism is not clear so far, some people think that climatic factors can affect the human nervous system, endocrine fluids The pH value, the balance of potassium and calcium, and the immune mechanism, etc., excessive cations in the air can also cause changes in potassium and calcium in the blood, leading to contraction of the bronchial smooth muscle.

7. There are serious complications or complications

Such as complicated pneumothorax, mediastinal emphysema or accompanied by cardiogenic asthma attacks, renal failure, pulmonary embolism or intravascular thrombosis can make asthma symptoms worse.

Asthma persistence prevention

Prevention of asthma should include:

1 eliminate or avoid various factors that produce allergies and asthma;

2 early diagnosis, early treatment;

3 actively control airway inflammation and symptoms, prevent the disease from worsening, and avoid complications.

1. Prevent the occurrence of asthma - primary prevention

As mentioned above, asthma in most patients (especially children) is allergic asthma, and the immune response of the fetus is a Th2-preferred response. In the late pregnancy, certain factors such as excessive maternal contact with allergens, viral infections It can enhance the Th2 response and aggravate the imbalance of Th1/Th2. If the mother is an allergic constitution, it is more obvious and should be avoided as much as possible. In addition, there is sufficient evidence to support the mother's smoking to increase the wheezing of infants after birth. And the risk of asthma, and breastfeeding for 4-6 months after birth can reduce the incidence of allergic diseases in infants, and mothers should avoid smoking during pregnancy. These are important links to prevent asthma, related to maternal diet. The impact on the fetus still requires more observation.

2. Avoid allergens and motivating factors - secondary prevention

(1) Avoid allergens: especially for patients with specific constitution, eliminate or avoid contact with factors that induce asthma, such as house dust mites, pollen, animal skin, foods that can cause allergies, drugs, etc. Asthmatic patients should be separated from the occupational environment.

As mentioned above, whether allergens of respiratory virus are asthma is still controversial, but it is closely related to the occurrence and development of asthma, especially respiratory syncytial virus in children, rhinovirus in adults, and avoiding respiratory virus infection is also important. Measures to prevent asthma.

(2) Prevention and treatment of allergic rhinitis: Allergic rhinitis has a close relationship with asthma. Some patients with allergic rhinitis have been followed for nearly 20 years, and found that nearly 17% of them develop asthma, which is much higher than the control group. (5%); studies have also shown that 20% to 25% of patients with simple allergic rhinitis have airway hyperresponsiveness (histamine or methotrexate challenge), so that these patients may be considered "subclinical" Asthma", asthma patients with allergic rhinitis accounted for about 28% to 50%, recent data indicate that such patients can actively control rhinitis on the basis of tracheal inhaled corticosteroid treatment (such as oral non-sedating H1 Receptor blockers, nasal inhaled corticosteroids can significantly reduce the frequency of asthma attacks and reduce their symptoms, so active treatment of allergic rhinitis is valuable for the prevention of asthma and reduce its onset.

3. Early diagnosis and treatment, control symptoms, prevent disease development - tertiary prevention

(1) Early diagnosis and early treatment: Patients with symptoms that are not obvious or atypical (such as manifested as simple cough, paroxysmal chest tightness or shortness of breath after exercise) should be diagnosed early. The study shows that for patients with confirmed bronchial asthma, The earlier the use of airway anti-infective therapy (inhaled corticosteroids), the lower the damage to future lung function (including the recovery of lung function and the increase in children's lung function with age), and thus the vast majority of patients (except a few) Intermittent "outside", once diagnosed, anti-infective treatment is required. With the standardization of specific immunotherapy, it may become an effective measure for tertiary prevention in patients with allergic asthma.

(2) Do a good job in education management for asthma patients: Asthma is a chronic disease. There is no cure at all. However, effective prevention and treatment measures can promote normal life, work, study and strengthen the education and management of patients. Important, first, educate patients to understand the nature of asthma, the incentives, the signs of the attacks, the types and methods of medication, especially the long-term anti-inflammatory prophylactic treatment, and second, the education patients learn to use the micro-peak flow meter to monitor Your own condition, in order to use the drug in time when the condition changes.

China has gained good experience in implementing the global asthma prevention and control strategy, especially the establishment of the Asthma Home. The Asthma Club has strengthened the cooperation between doctors and patients, making the frequency of asthma attacks, emergency rate and hospitalization rate, and medical expenses. Significantly reduced, and will be further promoted nationwide in the future.

Asthma persistent complication Complications emphysema pulmonary heart disease

Sustained state of asthma can cause chronic obstructive pulmonary disease, emphysema, pulmonary heart disease, heart failure, respiratory failure and circulatory failure, mucus fistula obstruction, etc., is a more common complication. The lung function of most asthma patients gradually worsens within a few days, but there are also a small number of patients with acute exacerbation of asthma that evolve rapidly, and respiratory and circulatory failures can occur within minutes to hours. Lactic acidosis occurs.

Symptoms of persistent asthma symptoms Common symptoms Breathing sounds weakened dyspnea Three concave signs irritability Wheezing tachycardia tachycardia Qimai fatigue chest and abdomen contradictory movement

The clinical manifestations of patients with persistent asthma status are: patients can not be supine, mood aroused, irritability, sweating, speech inconsistency, breathing > 30 times / min, full thoracic, decreased range of motion, assisted respiratory muscles involved in work (chest lock Papillary muscle contraction, three concave sign), heart rate > 120 times / min, often appear odd pulse (> 25mmHg), can appear in adults, PEF is lower than the best value of 60% or <100L / min, PaO2 <60mmHg, PaCO2>45mmHg, blood pH decreased, X-ray showed excessive lung inflation, pneumothorax or mediastinal emphysema, ECG can be pulmonary P wave, right axis deviation, sinus tachycardia, more critically ill people sleepiness or confusion, The chest and abdomen are contradictory (the diaphragmatic fatigue), and the wheezing sound can change from obvious to disappear.

The lung function of most asthma patients gradually deteriorates within a few days, but there are also a few patients with acute exacerbation of asthma, and the respiratory and circulatory failures can occur within a few minutes to several hours, so some people will have acute respiration. Depleted asthma is divided into two categories, acute severe asthma and acute asphyxia asthma.

Asthma status check

Blood gas analysis PaO2 <8.0KPa, PaO2>5.33KPa, pH value decreased.

Ordinary fluoroscopy showed that the X-ray showed excessive lung inflation, pneumothorax or mediastinal emphysema. The electrocardiogram showed pulmonary P wave, right axis deviation, and sinus tachycardia.

Diagnostic identification of asthma status

Diagnostic criteria

1. According to the medical history, there are factors that induce the persistent state of asthma.

2. Clinical manifestations, severe episodes of dyspnea lasted for more than 24 hours, and there were disturbances of consciousness, obvious cyanosis, severe inspiratory tri-concave signs, asthmatic sounds, decreased or disappeared breath sounds, decreased blood pressure, etc., plus ECG, lung function An abnormality can be diagnosed.

Differential diagnosis

Asthmatic patients do not necessarily show signs of wheezing. Conversely, they have wheezing and difficulty breathing. They may not be diagnosed with asthma and need to be identified with the following diseases.

Cardiogenic asthma

Early left ventricular dysfunction often has nocturnal dyspnea, and the symptoms associated with expiratory wheezing resemble bronchial asthma. These patients often have obvious history and signs of heart disease, and most of them have a sitting breathing, which may have diffuse lungs. Signs such as fine wet sputum, when it is difficult to identify, can be inhaled selective 2 receptor agonist for diagnostic treatment.

2. Spontaneous pneumothorax

Pneumothorax appearing on the basis of chronic obstructive pulmonary disease, pneumothorax signs are often not obvious, but manifested as sudden dyspnea, some patients with expiratory wheezing (especially contralateral pneumothorax), clinically easy to be confused with asthma, To be vigilant, suspicious individuals should be X-rayed early to confirm the diagnosis.

3. Atmospheric obstructive disorders

Tumors, foreign bodies, inflammation and congenital anomalies can cause obstruction of the larynx, glottis, trachea or main bronchus (intracavitary or external pressure), causing difficulty in breathing and wheezing, but this wheezing sound is often in a certain part. Particularly obvious, mostly biphasic wheezing sounds mainly in inspiratory phase, often accompanied by abnormal thickening of bronchial sounds at the end of the lungs, throat examination, X-ray tracheal forefront tomography and fiberoptic bronchoscopy can confirm the diagnosis.

4. Exogenous allergic alveolitis

This disease can present typical asthmatic manifestations, but these patients often have history of exposure to allergens (wild weeds, pigeon droppings, etc.), diffuse interstitial lesions with patchy infiltration of X-ray chest radiographs, significant blood eosinophils Increased to help identify.

5. Acute, chronic bronchitis

Such patients may have wheezing and dyspnea, and asthma patients may have no wheezing and only a paroxysmal dry cough, which is sometimes difficult to identify clinically, but the symptoms of bronchitis patients have no seizure characteristics, chronic bronchitis has Long-term chronic cough, bronchitis and cough are generally more, bronchodilator inhalation test or day and night PEF volatility measurement is helpful to identify.

6. Allergic bronchopulmonary aspergillosis ABPA

Often characterized by repeated asthma, with cough, cough, phlegm, mucus purulent, sometimes accompanied by bloodshot, can be separated from brown-yellow sputum, often with low fever, the lungs can hear wheezing or dry snoring, X Line examination showed infiltrative shadow, segmental atelectasis, toothpaste sign or finger sign (bronchial mucus embolism), peripheral blood eosinophils increased significantly, aspergillus allergen skin prick can appear biphasic skin reaction (immediately And delayed hair), serum IgE levels are usually more than 2 times higher than normal.

7. Gastroesophageal reflux (GER) postnasal drip syndrome (PNDS)

In esophageal achalasia, phlegm and other diseases, the stomach or duodenal contents often flow into the esophagus through the lower esophageal sphincter. The reflux is mostly acidic. As long as a small amount is inhaled into the trachea, it can be stimulated. Airway receptors reflexively cause bronchospasm through the vagus nerve, and cough and wheezing occur. It is reported that the incidence of GER in patients with severe asthma can approach 50%, indicating that GER is at least causing asthma patients to have seizures and symptoms are difficult to control. The important cause of targeted treatment of GER can significantly improve asthma symptoms.

Postnasal drip syndrome (PNDS), common in chronic sinusitis, its secretions often enter the trachea through the posterior nasal passages when the patient is lying down, can cause asthma-like cough and wheezing symptoms, and is also a recurrence of some asthma patients and An important factor in poor efficacy.

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