What Are the Pros and Cons of Prednisone for Asthma?

The 2014 GINA guidelines define asthma: Asthma is a heterogeneous disease, often characterized by chronic airway inflammation, and includes a history of respiratory symptoms that change over time, such as wheezing, shortness of breath, chest tightness, and cough, with variable expiration Restricted airflow.

Basic Information

English name: steroid resistant asthma
Visiting department: Respiratory

Common causes: Increased expression of hormone receptor (GR) subunits, increased expression of transcription factor activating peptide-1 (AP-1), etc.
Common symptoms: Severe airway hyperresponsiveness, nocturnal wheezing

Causes and pathogenesis of hormone-resistant asthma

1. Increased expression of hormone receptor (GR) subunits

GR can inhibit the hormone-responsive reporter gene action of GR, and this effect is concentration-dependent. GR may be an intrinsic inhibitor of hormone action, can affect the sensitivity of various tissues to hormones, and has a certain role in the formation of GRA.

2. Increased expression of transcription factor activating peptide-1 (AP-1)

Transcription factors are proteins that bind to the promoter of inflammatory protein genes, and they are activated by inflammatory stimuli such as cytokines. Most of the effects of hormones in treating asthma are achieved by inhibiting the abnormal expression of transcription factors such as AP-1 and NF-B. AP-1 overexpression can lead to hormone resistance.

3. Abnormalities of heat shock protein 90 (HSP90)

Hormones work by binding to the GR of the target cell cytoplasm. Normally, intracellular GR binds to two HSP90s. When the ratio of HSP90 / GR is appropriate, it appears as a positive regulation; while the ratio of HSP90 / GR is too high or too low, it is a negative regulation. The level of HSP90 gene expression increased, and the inhibitory effect of hormones on inflammation decreased.

4. The role of cytokines

IL-2 and IL-4 can maintain resistance to hormones by reducing the binding of GR to the ligand, and IL-13 has a similar effect.

5. High-Dose 2 Receptor Agonists

It can reduce the binding of glucocorticoid receptor (GR) and DNA and has antihormonal activity. Inhalation of 2 receptor agonists can reduce the effect of endogenous hormones and exacerbate asthma in patients who do not receive hormone therapy.

Clinical manifestations of hormone-resistant asthma

Compared with hormone-sensitive asthma (GSA), patients with hormone-resistant asthma (GRA) are older, have a longer history, have more severe airway hyperresponsiveness, and are more prone to nocturnal wheezing. In the clinic, asthma patients who have not used sufficient hormones to control symptoms should be alert to early detection and diagnosis of GRA, avoid unnecessary use of hormones, and take other alternative effective treatments to control asthma attacks.

Hormone-resistant asthma test

Laboratory inspection

Increased blood eosinophil counts are common.

2. Other auxiliary inspections

There were no obvious abnormalities in the chest X-ray, and the pulmonary ventilation test was the same as GSA.

Diagnosis of hormone-resistant asthma

1. GRA can be diagnosed according to the above definition and meet the following conditions at the same time

(1) The diagnosis of asthma is clear.

(2) The amount of hormones is sufficient. Patients regularly take hormones to ensure that sufficient doses of hormones reach the airways.

(3) No irritants in the living environment, especially indoor allergens or occupational allergens.

(4) Exclude potential asthma exacerbating factors such as gastroesophageal reflux and drugs.

(5) Stop ₂ receptor agonist.

(6) Severe asthma must be ruled out for at least 6 months after the abnormality of its lung function.

2. Exclude certain factors that cause hormone resistance

(1) Patients with GSA but poor response, such as poor medication compliance, insufficient hormone dosage or short medication time, poor drug delivery device quality, failure to terminate exposure to pathogenic factors, etc.

(2) Those with other diseases misdiagnosed as GRA, such as gastroesophageal reflux disease, lack of complement C1 inhibitors, vocal cord dysfunction, etc.

(3) Asthma secondary to asthma induced by other causes, allergic bronchopulmonary aspergillosis, Churg-Strauss syndrome, etc.

(4) Asthma caused by drug-related asthma beta-blockers, non-steroidal anti-inflammatory drugs, and angiotensin-converting enzyme inhibitors.

Hormone-resistant asthma treatment

Bronchodilator

Bronchodilators are first-line medications and can be administered by inhalation, oral, subcutaneous or intravenous routes. Long-acting beta receptor agonists can significantly dilate the bronchi and should be used in combination with other non-hormonal antiallergic drugs. Inhaled anticholinergic drugs have a good effect in some patients with GRA. Oral or intravenous injection of theophylline can show a significant bronchodilator effect in refractory asthma. Leukotriene modulators have a good effect in some patients, especially those with airway disease or allergic to aspirin.

Glucocorticoid

GRA patients are very responsive to long-term oral or intravenous application of large doses of hormones, and the therapeutic value of hormones is very limited at this time. However, a small number of patients also show a certain degree of responsiveness in the case of ultra-high-dose hormones. These patients can try the ultra-high-dose hormones for a short time. However, side effects such as Cushing's syndrome are likely to occur with super-dose hormones. Recently, new hormone preparations such as RU24858 and RU40066 are expected to play a role in the treatment of GRA asthma. The current inhaled preparations fluticasone and budesonide used in the treatment of asthma have strong anti-inflammatory effects, and have obvious "first pass effects", thereby reducing the systemic effects of hormones and can be applied clinically.

3. Methotrexate

Methotrexate can inhibit the airway's response to inflammatory mediators such as histamine and has a significant anti-inflammatory effect. Low-dose methotrexate can significantly reduce hormone dosage in patients with severe hormone-dependent asthma. The main side effect of methotrexate is the reaction of the digestive system, and hepatotoxicity in large doses. It may also inhibit bone marrow, kidney damage, and rashes. Medications used in early pregnancy can cause fetal dysplasia, miscarriages, stillbirths, or teres. However, no serious side effects have been reported for low-dose asthma treatment.

4.Cyclosporine

Cyclosporine can significantly reduce the amount of hormones used in patients with hormone-dependent asthma, improve asthma symptoms and reduce asthma attacks, but asthma will still recur after stopping cyclosporine, so it needs to be used for a long time. The main side effects of cyclosporine are nephrotoxicity and hypertension, as well as hairiness, peripheral neuritis, liver toxicity, and headache. Although cyclosporine theoretically and clinically seems to be the ideal drug for the treatment of GRA, its potential side effects and high drug prices limit its widespread use.

5. Immunoglobulin

Intravenous immunoglobulin treatment of patients with severe hormone-dependent asthma can reduce hormone dosage, improve clinical symptoms and PEF, and weaken skin response to specific allergens. However, there is a lack of research data on the dosage and frequency of application, and its price is more expensive.

6. Leukotriene

Leukotriene modulators can significantly reduce the number of eosinophils in blood and sputum and improve the symptoms of asthma. Its inhibition of asthma inflammation is completely different from that of hormones and can be used to treat GRA.

7. Other drugs

Auranofin, dapsone, hydroxychloroquine, and triacetylmycin are used in the treatment of hormone-dependent asthma, which can alleviate the symptoms of asthma, reduce the amount of hormones, and have certain application value in the treatment of GRA asthma.