hormone-resistant asthma
Introduction
Introduction to hormone-resistant asthma Glucocorticoids have been widely used as first-line treatments for asthma. Most patients with asthma have a significant improvement in clinical symptoms and pathophysiological changes in a short period of time with large doses of prednisone. For children with initial diagnosis of asthma in adults and adults, Both high-dose and low-dose inhaled hormones can alleviate symptoms and improve lung function. However, not all asthma patients have shown efficacy in the treatment of hormones. Some patients have long-term or high-dose hormones, which is not satisfactory. This is glucocoticoid resistant asthma (GRA). In addition to the need to clarify the rules for the diagnosis of hormone-resistant asthma, it is necessary to eliminate the factors that lead to hormone resistance and strict differential diagnosis. Bronchodilators are the first-line drugs for the treatment of hormone-resistant asthma. Asthma that shows good effects on hormones is glucocoticoidsensitiVeasthma (GSA). basic knowledge The proportion of illness: 0.005% Susceptible people: no specific population Mode of infection: non-infectious Complications: Hormone-resistant asthma
Cause
Hormone-resistant asthma
(1) Causes of the disease
Some patients have long-term or high-dose hormones, and their efficacy is not satisfactory. This is hormone-resistant asthma.
(two) pathogenesis
1. Increased expression of hormone receptor (GR) subunit
GR can inhibit the action of hormonal response reporter gene of hormone-activated GR, and this effect is concentration-dependent. GR may be an intrinsic inhibitor of hormonal action, which can affect the sensitivity of various tissues to hormones during the formation of GRA. Has a certain effect.
2. Increased expression of transcription factor activating peptide-1 (AP-1)
Transcription factors are proteins that bind to the promoter of inflammatory protein genes. They are activated by inflammatory stimuli such as cytokines. The role of hormones in the treatment of asthma is mostly through the inhibition of transcription factors such as AP-1, NF- By the abnormal expression of B, AP-1 overexpression can lead to hormonal resistance.
3. Abnormal heat shock protein 90 (HSP90)
The hormone acts by binding to the GR of the target cell cytoplasm. Under normal conditions, the intracellular GR binds to two HSP90s, and when the ratio of HSP90/GR is appropriate, it is positively regulated; and the ratio of HSP90/GR is too high or too high. Low is negative regulation, HSP90 gene expression level is increased, and hormone inhibition of inflammation is decreased.
4. The role of cytokines
IL-2 and IL-4 maintain resistance to hormones by reducing the binding of GR to ligands, and IL-13 has a similar effect.
5. High dose 2 receptor agonists
High-dose 2-receptor agonists can reduce the binding of GR to DNA and have anti-hormone activity. Inhalation of 2-receptor agonists can reduce the action of endogenous hormones and aggravate asthma in patients who do not inhale hormone therapy. Inhalation of large doses of 2-receptor agonists also reduces the effects of inhaled hormonal therapy and forms relatively resistant hormones.
Prevention
Hormone-resistant asthma prevention
Clinical health workers should be alert to asthma patients who have not been able to control symptoms with adequate doses of glucocorticoids in order to detect and diagnose hormone-resistant asthma early, and stop unnecessary use of glucocorticoids in time to avoid side effects caused by hormones.
Complication
Hormone-resistant asthma complications Complications hormone-resistant asthma
Long-term high-dose hormonal therapy can increase liver alanine aminotransferase, aspartate aminotransferase complications, and other patients with hormone-resistant asthma have abnormal skin vasoconstriction response to hormones.
Symptom
Hormone-resistant asthma symptoms Common symptoms Stressful airway hyperresponsiveness
Definition
At present, there is no uniform standard for the diagnosis of GRA. The difference between different standards is mainly due to the difference between the dose of hormone therapy and the duration of treatment. GRA is generally defined as: FEV1 as a percentage of predicted value (FEV1/pre%) 75 % of asthma patients with appropriate doses of hormone (such as oral prednisone 40mg / d) after 2 weeks of treatment, the improvement of FEV1 15% can be defined as GRA; on the contrary, if the increase of FEV1 > 15% Can be defined as GSA.
2. Clinical features
Compared with GSA, GRA has the characteristics of older age, longer medical history, more severe airway responsiveness, and more prone to nocturnal wheezing. It should be improved in clinical work for asthma patients who have not been able to control symptoms after using full-dose hormones. Be alert to detect and diagnose GRA early, avoid unnecessary use of hormones in a timely manner, and take other alternative effective treatments to control asthma attacks.
3. Hormone-dependent asthma
Clinically, some patients with asthma need long-term application of hormones to control symptoms, which is called hormone-dependent asthma. When such patients take oral hormone reduction, their condition deteriorates. Very few patients need to take prednisolone 40mg daily to maintain treatment, which is easily misdiagnosed as GRA.
Examine
Hormone-resistant asthma check
Laboratory examination: peripheral blood eosinophils increased.
There was no obvious abnormality in the chest X-ray.
Diagnosis
Diagnosis of hormonal resistance asthma
Diagnostic criteria
1. Can diagnose GRA according to the above definition and at the same time meet the following conditions
(1) The diagnosis of asthma is clear.
(2) The amount of hormone is sufficient, and the patient regularly takes hormones to ensure that a sufficient dose of hormone reaches the airway.
(3) There are no irritants in the living environment, especially indoor allergens or occupational sensitizers.
(4) Exclude potential asthma exacerbations such as gastroesophageal reflux and drugs.
(5) The 2 receptor agonist is stopped.
(6) Severe asthma must be excluded from the abnormal state of lung function itself at rest for at least 6 months.
2. Exclude certain factors that cause hormone resistance
(1) Patients with GSA but poor response: if medication compliance is poor, hormone dose is insufficient or medication time is short, the quality of the drug delivery device is not good, and the exposure to pathogenic factors cannot be terminated.
(2) Other lesions misdiagnosed as GRA: such as gastroesophageal reflux disease, nasal secretions, lack of complement C1 inhibitors, vocal cord dysfunction.
(3) Asthma secondary to other causes: aspirin-induced asthma, allergic bronchopulmonary aspergillosis, Churg-Strauss syndrome, etc.
(4) Drug-associated asthma: asthma caused by beta blockers, non-steroidal anti-inflammatory drugs and angiotensin-converting enzyme inhibitors.
Differential diagnosis
1. Upper airway obstruction secondary to vocal tract dysfunction
It is rare in clinical practice, and its clinical manifestations are very similar to asthma, but vocal cord dysfunction can be diagnosed by combined detection of flow-capacity loop and vocal cord abnormal adduction movement during endoscopic direct inhalation.
2. Esophageal reflux disease
It is important in refractory asthma by micro-aspiration or stimulation of vagal excitability. Studies have shown that 34% to 89% of asthma patients have gastroesophageal reflux, but not necessarily clinical symptoms, combined with esophageal reflux disease Asthma patients are usually accompanied by abnormal esophageal tension, local inflammatory response persists, the number of reflux per hour increases, each reflux time is extended, the pH value in the esophagus is <4, and the esophageal pH can be monitored for 24 hours when considering esophageal reflux disease. The diagnostic sensitivity and specificity were 95% and 93%, respectively. If the result is positive, the proton pump inhibitor phenylpropimazole can be administered orally for 3 months.
3. Recurrent hemorrhagic edema in the upper respiratory tract
It can cause asthmatic symptoms in patients. In this case, wheezing rather than wheezing is the main symptom, which is related to facial edema, skin urticaria, etc. If this diagnosis cannot be determined, the content of complement and its content can be detected. Function to rule out complement C1 inhibitor deficiency.
4. Drops after nasal secretions
This is more common in asthma patients, often secondary to sinus disease, nasal secretions can cause repeated cough, and the treatment of nasal secretions also significantly contribute to the control of asthma.
5. Symptoms of asthma symptoms
Extremely difficult to handle and dangerous, so far there is no very reliable diagnostic method.
6. Inappropriate use of asthmatic drugs induces asthma or systemic disease with asthma manifestations
(1) -blockers can induce the first episode of asthma, and can also cause asthma in the primary diagnosis to be further aggravated and more difficult to treat.
(2) Aspirin, or more accurately, allergic symptoms of non-steroidal anti-inflammatory drugs involving 5% to 30% of asthma patients, facial flushing, asthma, rhinitis and other typical manifestations usually in oral aspirin or other non-steroidal anti-inflammatory drugs After 30 minutes to 2 hours, this phenomenon is very obvious even when using highly cardiovascular selective beta blockers or ophthalmology using a small amount of beta blockers. Once you realize this problem, you can choose other Another alternative treatment is cough caused by angiotensin-converting enzyme inhibitors, and other alternatives should be used in this case.
Churg-Strauss syndrome can also have asthma symptoms. Patients with original asthma diagnosed with rhinitis, skin damage, and systemic symptoms such as weight loss should consider the possibility of Churg-Strauss syndrome. Abnormalities in laboratory tests include peripheral blood and tissues. The levels of eosinophils, erythrocyte sedimentation rate, and anti-neutrophil cytoplasmic antibodies were significantly increased.
