What Is Silent Acid Reflux?

Reflux asthma is one of the extraesophageal manifestations of gastroesophageal reflux disease. The consensus reached at the time included: (1) the interaction between asthma and GERD; (2) asthma is often a multifactorial disease process, and GERD can aggravate it; (3) GERD is rarely a single cause of asthma; (4) Asthma may have a direct or indirect effect on GERD; (5) if there is no heartburn or reflux symptoms, asthma of unknown origin may not be related to GERD; (6) drugs and surgical treatments for GERD, and comprehensive treatment of hypothetical reflux asthma Efficacy is uncertain.

Reflux asthma

Reflux asthma is one of the extraesophageal manifestations of gastroesophageal reflux disease. The consensus reached at the time included: (1) the interaction between asthma and GERD; (2) asthma is often a multifactorial disease process, and GERD can aggravate it; (3) GERD is rarely a single cause of asthma; (4) Asthma may have a direct or indirect effect on GERD; (5) if there is no heartburn or reflux symptoms, asthma of unknown origin may not be related to GERD; (6) drugs and surgical treatments for GERD, and comprehensive treatment of hypothetical reflux asthma Efficacy is uncertain.

The pathogenesis of reflux asthma

Esophageal-bronchial reflex

The esophagus and bronchial tree share common embryonic origin and autonomic innervation. It is based on the embryonic intestine of the common origin of the gastrointestinal tract (including stomach and esophagus) and bronchial development. The afferent neural pathways of the esophagus and lung are dominated by the vagus nerve originating from the solitary nucleus of the midbrain, and the interneurons are connected to the motor neurons in the suspected nucleus region of the ventrolateral medulla. Reflux and acid stimulate various machinery in the esophagus Receptors and chemoreceptors affect the trachea through vagus nerve reflex. Gastroesophageal reflux foods and fluids (mainly acidic) inhaled into the bronchi are important causes of asthma. Frequent reflux can cause obvious inflammation of the posterior pharyngeal wall. Acid reflux counteracts acid-sensitive receptors exposed to inflammation in the esophageal mucosa, improves airway responsiveness through the vagus nerve response, and increases the tension of bronchial smooth muscle, leading to recurrent asthma. Therefore, for patients with chronic cough and asthma who have been cured for a long time, the presence of GERD must be considered. Animal experiments found that [3], lung function of healthy dogs was significantly reduced after acid injection into the esophagus, but no significant changes in lung function were found after cutting the vagus nerves on both sides of the cervical dorsal root. Therefore, the vagus nerve reflex may play an important role in the mechanisms of reflux and acid-triggered bronchoconstriction.

2. Trace or massive acid reflux

Due to GERD, bronchial and lung effector-target cells inhaled acidic microparticles, resulting in increased bronchial and pulmonary vascular permeability, pulmonary edema, increased bronchial secretions, bronchospasm, airway obstruction, and asthma attacks. Some authors believe that the reflux of gastric acid in the trachea directly stimulates the tracheal mucosa is the main mechanism that causes asthma and cough. Due to the special anatomical relationship between the esophagus and the trachea, the reflux can directly enter the trachea through the esophagus, reducing the pH in the trachea, causing bronchospasm through axonal reflection, and increasing lung resistance; at the same time, the acidic gastric contents entering the airways stimulate and Damage the respiratory tract mucosa and produce chemical inflammation. In addition, gastrointestinal bacteria can enter the respiratory tract with food, causing respiratory bacterial inflammation. However, these reflux fluids are usually difficult to confirm. Although gastroesophageal scintigraphy or scan scans are used to monitor reflux episodes, they are more specific but less sensitive. Daoui et al. Expounded the mechanism of tracheal microvascular dilatation and plasma exudation caused by acid-induced release of tachykinin (including substance P, neurokinin A, and neurokinin B) in tracheal nerve fiber terminals through animal experiments. After instillation of dilute hydrochloric acid in the esophagus of healthy pigs and rabbits, tracheal plasma exudation was 3 and 5 times that of the control group without acid infusion, respectively, and neurokinin (NK) receptor antagonists were used. Later, tracheal plasma exudation did not increase. It can be confirmed that acidic stimulation of the trachea causes microvascular dilatation and plasma exudation is mainly achieved by the release of tachykinin, while neurokinin 1 (NK1) and neurokinin 3 (NK3) receptors are also involved in this complex process . Another study found that while airway acid exposure caused bronchoconstriction, the protective substance of nitric oxide (NO) was released, and the NO synthetase inhibitor N (G) -nitro-L-arginine methyl ester ( L-NAM E) significantly increased bronchoconstriction. Therefore, NO may also play an important role in it. At present, although there are many hypotheses to explain the airway contraction caused by acid reflux, the exact mechanism is still unclear and needs further study.

3. Bronchial hyperresponsiveness

Airway hyperresponsiveness is a major feature of asthma. Its main formation mechanism is: 1 acid reflux to stimulate acid-sensitive receptors exposed to inflammation in the esophageal mucosa and improve airway responsiveness through the vagus nerve response. 2 The regurgitant is inhaled into the lungs, which directly stimulates and damages the airway mucosa, leading to inflammatory reactions and increased airway responsiveness, which increases the sensitivity of asthma patients to various triggering factors. Li Qinzi et al. [6] found that by injecting hydrochloric acid into the middle and lower esophagus of the target guinea pigs for 14 days, acetylcholine oxide was injected intravenously for a tracheal challenge test. With the doubling of acetylcholine, there was a significant difference between the experimental group and the control group. Guinea pig esophagus was repeatedly perfused with hydrochloric acid, and airway resistance was significantly increased with the doubling of acetylcholine. Stein et al. [7] considered that airway hyperresponsiveness is the ultimate pathway for bronchial asthma caused by GERD. When the airway is stimulated by reflux, the involvement of a variety of inflammatory cells, inflammatory mediators and cytokines, as well as damage to the airway epithelium and exposure of subepithelial nerve endings, can induce vagal reflex and neurogenic inflammation, resulting in AHR and respiratory symptoms. Xiao Xu [8] improved gastroesophageal reflux through cisapride and observed changes in lung function before and after treatment. As the symptoms of gastroesophageal reflux improved, lung function also improved. The two were positively correlated, indicating gastroesophageal reflux It has an effect on tracheal hyperresponsiveness. It is speculated that gastroesophageal reflux enters the airway through epiglottis, which may aggravate the chronic inflammatory process of the airway, suggesting that the influence of physical, chemical, and biological factors on airway hyperresponsiveness cannot be ignored.

Airway inflammation

The human airway is densely distributed with nerve fibers. Under a series of noxious stimuli, peripheral nerve endings can release immediate and slow irritants through axonal reflexes. These neurotransmitters can directly or indirectly stimulate nerves on the tracheal wall. Skin receptors, which trigger an inflammatory response. Under the action of inflammation, a series of defensive reflexes such as bronchospasm, excessive secretion of mucus, vasodilation, and plasma exudation occur in the airway. In addition, the stimulation of allergens can lead to an increase in nerve growth factor (NGF) in the nasal cavity, and animal experiments have shown that NGF can cause airway type A fibers to transform into central nervous system excitement and peripheral neurogenic inflammation Tachykinin expression fibers. And animal experiments have confirmed that increased hydrogen ion concentration and changes in osmotic pressure can induce neurogenic inflammation. Some researchers have also confirmed that in guinea pig models, acid in the esophagus can activate local axonal reflex, that is, the acid in the esophagus causes the bronchial mucosa to release inflammatory mediators (such as substance P) through local nerve reflex, leading to airway edema. Lai Yungang [9] and other studies found that GERD-derived "asthma" airway inflammation is mainly characterized by neutrophil infiltration and IL-8 elevation, which is different from asthma with eosinophil infiltration and IL-5 elevation. Primary airway inflammation. When combined with asthma, GERD can promote the existing airway inflammation of asthma through the action of the above cytokines, and then aggravate its course. It can be seen that airway inflammation also plays an important role in the mechanism of asthma caused by gastroesophageal reflux, which provides a theoretical basis for kinin and bradykinin antagonists in the treatment of patients with gastroesophageal reflux asthma.

5. Internal organs are highly sensitive.

Characteristics of reflux asthma

Patients often have clinical manifestations of gastroesophageal reflux such as acid reflux, heartburn, bloating, and heating, but there are also a considerable number of patients who have only mild acid reflux or heartburn, and even have no digestive symptoms, which is called "silent" Gastroesophageal reflux disease, which brings great difficulties to the diagnosis of gastroesophageal reflux-induced asthma. Generally speaking, gastroesophageal reflux-derived asthma mostly has the following characteristics, such as: wheezing is mainly difficult to breathe; cough and wheezing have no obvious seasonality; cough and wheezing are mainly at night; cough Asthma is prone to occur in the supine position, which can be relieved after sitting up. Cough and asthma are prone to occur after eating or eating spicy food; Qi can be reduced or relieved after heating; Laryngitis of unknown cause , Highly suspected of gastroesophageal reflux caused by dry throat, itching, foreign body sensation, hoarseness, recurrent laryngeal spasm, etc .; other extra-esophageal manifestations of gastroesophageal reflux, such as reflux Rhinitis, sinusitis, otitis media, tooth erosion, etc .; Negative allergen test or contact with the allergen did not cause cough and asthma; chest radiograph, chest CT and other no lung lesions.

Reflux asthma diagnosis

Auxiliary examination: gastroscopy: to know whether there is esophageal erosion and the degree of erosion, and whether the cardia is loose;

24-hour esophageal pH monitoring: For non-erosive gastroesophageal reflux disease without mucosal damage, this test is the "gold standard" and can determine whether "asthma" symptoms are related to reflux;

Esophageal pressure measurement: It is of great significance for the diagnosis of esophageal dyskinesia;

Intraesophageal impedance monitoring: reflux can be detected with p H> 4, and it can be determined whether the symptoms of "asthma" are related to reflux;

The above four methods are all effective methods for diagnosing gastroesophageal reflux. The 24-hour pH monitoring of the esophagus and the impedance monitoring of the esophagus cavity combine the reflux event with the patient's symptoms, which is helpful for "asthma" symptoms and reflux. Determination of relevance.

For those with atypical symptoms and no positive findings from the above auxiliary tests, but clinically suspected of gastroesophageal reflux-induced asthma, a diagnostic drug test may be a good method. Proton pump inhibitor tests are usually performed in such a way that a standard dose of a proton pump inhibitor (such as omeprazole 20 mg) is administered twice daily for two to three months. If the patient's symptoms disappear or improve, this is an obvious acid-related disease. The test is reliable and simple, and has high clinical application value.

Reflux asthma treatment

I. Lifestyle changes and psychotherapy:

1. Lifestyle changes: In terms of lifestyle changes, in order to reduce the reflux that occurs at night and in the lying position, it is advisable to take a slope position (it is not enough to raise the head only) or raise the bed properly; eat slowly. To eat a small number of meals, do not stay in bed immediately after meals, and take a lying position at least 2 hours later; reduce the factors that cause increased abdominal pressure, such as not tightening the belt, avoid constipation and weight control; try not to eat high-fat foods, chocolate, Coffee, strong tea, and smoking cessation.

2. Psychotherapy: Gastrointestinal diseases are closely related to psychological factors. Psychological stimulating factors act on the brain, making the cerebral cortex dysfunctional, and then affecting the regulating function of the autonomic nervous system, causing sympathetic and parasympathetic nerve disorders, leading to gastrointestinal dyskinesia; in turn, severe gastrointestinal symptoms affect daily work and life It can cause emotional changes, aggravate gastrointestinal diseases, and form a vicious circle. Patients are often trapped and cannot extricate themselves. Patients have depression, and some even have suicidal tendencies. The key to psychotherapy is to first explain to the patient that it is not incurable and to have the confidence to cure. If the effect is not obvious, you can ask the psychologist for treatment.

Second, drug treatment: including two parts of gastrointestinal drugs and respiratory drugs.

1. Gastrointestinal drugs:

1.1 H2 receptor antagonists: such as cimetidine 800-1000 mg / d, divided into 4 times; ranitidine 300 mg / d, divided into 2 times; famotidine 40 mg / d, divided into 2 times; course of treatment 6-8 weeks, the symptoms are not satisfactory should be the full dose for 12 weeks. The treatment effect is not good, and it is gradually being replaced by proton pump inhibitors.

1.2 Proton pump inhibitors such as omeprazole 20mg 1 to 2 times daily, rabeprazole 20mg, 1 to 2 times daily, lansoprazole 30mg, 1 to 2 times daily, course of treatment 6 to 8e. Some studies have shown that the symptoms of GERD disappear rapidly in the treatment of proton pump inhibitors, and the cure rate at 8w is 74% to 96%, which is significantly higher than that of H2 receptor blockers.

1.3 Prokinetic drugs Gastroesophageal reflux disease is an upper gastrointestinal motility disease. Theoretically, the treatment should first improve the power, increase the LES tension, improve the esophageal clearance function, and increase gastric emptying. Commonly used prokinetic agents are domperidone (10 mg 3 times a day), cisapride (5-10 mg 3 times a day) and so on.

1.4 Mucosal protective agents When GERD causes esophageal inflammation, erosion or ulcers, the application of such drugs can cover the surface of the lesion to form a protective film, which can reduce symptoms and promote healing. Commonly used drugs are 1.0g aluminum magnesium carbonate tablets, 4 times a day, 15ml aluminum and magnesium suspensions, 3 times a day, 1h before meals and taken before bedtime. Its exact effect remains to be studied.

2. Respiratory drugs:

2.1 Bronchodilators. These drugs have the main function of dilating the bronchus and controlling the acute symptoms of asthma.

(2). Theophylline: The general dose of oral theophylline is 5-8mg / kg daily, and the sustained-release theophylline is 8-12mg / kg daily. Intravenous administration is mainly used in critically ill asthma. The first injection dose is 4-6mg / kg and it should be injected slowly. The injection time should be greater than 15min. The intravenous drip maintenance amount is 0.8-1.0mg / kg per hour. The daily dosage generally does not exceed 750mg-1000mg.

(3). Anticholinergic drugs: Ipratropine bromide, etc., can block the vagal nerve pathway after the festival, reduce the excitability of the vagus nerve and relax the bronchus, and can block the reflective bronchoconstriction. Combined with 2 agonist inhalation therapy, the bronchodilator effect is enhanced and lasting. It is mainly used in asthma patients whose 2 agonist alone does not control symptoms, and it is especially suitable for patients with chronic obstructive pulmonary disease. Can be inhaled with MDI or continuous nebulization, 3 to 4 times a day, 75 to 250 g each inhalation. It takes about 15 minutes and lasts for 6 to 8 hours. There are few adverse reactions, and a few patients have bitter or dry mouth.

2.2 Anti-inflammatory drugs or drugs called disease control. Because the pathological basis of asthma is chronic non-specific inflammation, controlling chronic airway inflammation is the basic treatment of asthma and plays an important role in the ideal long-term control of asthma. Commonly used drugs are inhaled glucocorticoids and chromones. Some new drugs, such as leukotriene modulators, long-acting 2 agonists, and controlled release theophylline, also have some anti-inflammatory effects.

(1). Glucocorticoids Glucocorticoids (hormones for short) are currently the most effective drugs for the prevention and treatment of asthma. The main mechanism of action is to inhibit the migration and activation of inflammatory cells; inhibit the production of cytokines; inhibit the release of inflammatory mediators; and enhance the reactivity of 2 receptors in smooth muscle cells. Can be divided into inhalation, oral and intravenous medication. Inhaled hormones are the most basic treatment to control the long-term stability of asthma, and are the first-line medications for asthma. Inhaled hormones increase the ester group through its molecular structure, which significantly increases the local anti-inflammatory titer. It acts locally on the respiratory tract. The dose used is small. The drug is quickly inactivated in the liver after entering the blood circulation and has fewer systemic adverse reactions . The main adverse reactions were oropharyngeal discomfort, oropharyngitis, hoarseness, or oropharyngeal candida infection. Rinse mouth with water after spraying can reduce local reactions. There are some differences in the incidence of oropharyngitis when using different inhalation dosage forms or drugs. Oropharyngitis usually recovers naturally after 4-7 days of discontinuation. Commonly used inhaled hormones are Beclomethasone Dipropionate (Beclomethasone Dipropionate), Budesonide, Flunisolide, and Triamcinolone Acetonide. In recent years, some new and more active inhaled hormones have been developed, such as Fluticasone. Its effect is increased by 2 times, and there are few side effects. Inhale with MDI, dry powder or continuous nebulization. The onset is slow, it takes long-term regular inhalation for more than one week before it becomes effective, and the best effect can be achieved by continuous application for more than 3 months. According to asthma, the inhaled dose is generally 200 1200g / d.

Oral or intravenous hormones are important treatments for moderate to severe asthma attacks. According to the needs of the disease, choose the appropriate dose and treatment course (see Table 1), gradually reduce and discontinue the symptoms, and apply inhaled hormones sequentially.

(2). Disodium tryptonate is a noncorticosteroid anti-inflammatory drug. The mechanism of action has not been fully elucidated. It can stabilize the mast cell membrane, inhibit the release of mediators, and also have a certain inhibitory effect on the release of other inflammatory cells. It can prevent rapid and delayed reactions caused by allergens and airway contraction caused by exercise and hyperventilation. Inhaled 5 to 20mg or dry powder inhaled 20mg 3 to 4 times a day. This product has no accumulation in the body. A few cases may have throat discomfort, chest tightness, and occasional skin rash. Pregnant women should use it with caution.

3 Other drugs leukotriene modulators include leukotriene receptor antagonists and synthesis inhibitors (5-lipoxygenase inhibitors). The cysteyl leukotriene receptor antagonists that can be successfully applied in clinical practice at present include Zaruth (Zafirlukast 20 mg twice daily) and Montelukast (Montelukast 10 mg once daily), which can not only relieve asthma symptoms, but also It can reduce airway inflammation and has certain clinical effects. It can be used in patients who cannot use hormones or in combination. The main adverse reactions are gastrointestinal symptoms, which are usually mild. A few have rash, angioedema, elevated transaminase, and can return to normal after stopping treatment. Long-acting 2 agonists or controlled release theophylline have no obvious anti-inflammatory effect when used alone, but combined with inhaled corticosteroids can significantly increase the anti-inflammatory effect of inhaled hormones.

3. Endoscopic minimally invasive treatment: radiofrequency treatment of esophagus microcurrent.

Fourth, surgical treatment: laparoscopic fundoplication.