| disease | Allergic Asthma |
| alias | Asthma |
Asthma is a chronic airway inflammation involving various cells such as mast cells, eosinophils, and T lymphocytes. Its clinical features include chronic airway inflammation, reversible airway obstruction, and increased airway reactivity. Clinically, it manifests as recurrent episodes of wheezing, shortness of breath, chest tightness, and/or cough, often occurring at night or in the early morning. This disease is common, with a prevalence rate of about 1% in China.
bubble_chart Etiology
The disease cause is complex, including genetic and environmental factors. The type I hypersensitivity reaction mediated by IgE-activated mast cells is an important factor in the pathogenesis, but it cannot explain all disease causes.
1. Genetic factors
The familial occurrence of the disease suggests that genetic factors are related to its onset. Many genes involved in the pathogenesis have been identified. The production of total IgE and specific IgE (sIgE), as well as airway hyperresponsiveness, are all controlled by specific genes. Studies indicate that genes controlling IgE reactivity are located on chromosomes 11q, 12q, and 13q, and allergic asthma is associated with DNA polymorphism at D11S97 on chromosome 11.
2. Triggering factors
There are many triggering factors for asthma. Based on the inducing causes, asthma can be classified into: allergic (accounting for 60% of asthma cases), which often begins in childhood, has a family history, and is frequently accompanied by other atopic allergies. About 30% may persist into adulthood, but fatalities are rare; idiopathic (accounting for 30% of asthma cases), which mostly occurs in individuals over 40 or infants, rarely accompanies other atopic allergies, has no family history, and unclear triggers. It may become chronic or even fatal; other types (accounting for 10% of asthma cases), with variable onset ages, rarely accompanying other atopic allergies, no family history, and triggers such as aspirin, Aspergillus, or cancer, with uncertain prognosis.
b. Respiratory infections Childhood respiratory infections are closely related to asthma onset. Infections by respiratory syncytial virus, adenovirus, rhinovirus, influenza virus, etc., can stimulate the production of specific IgE and directly trigger mast cells to release mediators. Additionally, airway epithelial injury and exposed nerve endings caused by viral infections are also associated with increased airway reactivity.
c. Triggering factors Air pollution, smoke, exercise, cold air stimulation, psychological stress, and social, familial, or psychological factors can all induce asthma. However, these factors may only act as catalysts for airway narrowing rather than the true disease cause.
d. Medications Drugs that can induce asthma mainly include aspirin-like medications (such as aspirin, indomethacin, metamizole, ibuprofen, etc.). Their mechanism involves inhibiting the cyclooxygenase pathway of arachidonic acid metabolism, reducing bronchial-dilating PGE2 and increasing leukotrienes (LT), among which LTC4, D4, and E4 have strong bronchoconstrictive effects. Beta-2 receptor blockers, such as propranolol, and local anesthetics, such as bupivacaine and lidocaine, may induce asthma by stimulating the vagus nerve. Angiotensin-converting enzyme inhibitors, such as captopril and enalapril, can degrade bradykininase, reducing bradykinin degradation.
bubble_chart PathogenesisThe pathogenesis of asthma is primarily attributed to type I hypersensitivity (allergic reactions), but type I hypersensitivity alone cannot fully explain phenomena such as airway hyperresponsiveness. Airway inflammation is the pathological basis of asthma.
When allergens enter the body, they are processed by antigen-presenting cells such as dendritic cells and presented to T cells. Under the interaction of CD28 on T cells with B7 molecules on dendritic cells and their secreted IL-1, IL-12, etc., T cells differentiate into Th2 cells. Th2 cells secrete IL-3, IL-4, IL-5, IL-13, TNF-α, and GM-CSF. Among these, IL-3, IL-5, and GM-CSF influence the differentiation, maturation, and survival of eosinophils, while IL-4, IL-5, IL-13, and TNF-α upregulate the adhesion molecule VCAM-1, which enables neutrophils, eosinophils, and monocytes to adhere to or migrate toward vascular endothelium. IL-4 and IL-13 promote the differentiation of B cells into IgE-producing cells, a process that requires effective signaling from the interaction between CD40 on B cells and CD40 ligand on T cells. Th1 cells secrete IL-2, IL-12, and IFN-γ, which inhibit IgE synthesis and the type I hypersensitivity reactions it mediates. Therefore, the imbalance in the ratio and function of Th1/Th2 cells plays a significant role in the pathogenesis of asthma. After IgE synthesis, it activates mast cells and eosinophils, causing them to degranulate and release inflammatory mediators, thereby triggering airway inflammation and subsequently asthma. When eosinophils in the airways are activated, they produce IL-8 and RANTES, attracting more eosinophils to infiltrate the inflammatory site.
Airway hyperresponsiveness is one of the hallmarks of asthma and is a consequence of airway inflammation. Airway inflammation leads to airway injury, resulting in epithelial shedding, exposed nerve endings, microvascular leakage, and smooth muscle contraction, all of which enhance the airway's reactivity to stimuli.
bubble_chart Pathological Changes
The main pathological changes of asthma include shedding of airway epithelial cells, mucosal edema, subepithelial fibrosis, hyperplasia and hypertrophy of smooth muscle, infiltration of eosinophils, monocytes, and mast cells in the bronchial mucosa, and thickening of the basement membrane. Histological changes mainly manifest as airway inflammation and epithelial injury. There may be tissue edema, thickening of the airway wall, capillary congestion, smooth muscle hyperplasia, and hyperplasia of submucosal glands. Fibrous deposits beneath the basement membrane, seen in long-term chronic asthma patients, can lead to irreversible airway obstruction.
bubble_chart Clinical Manifestations
The typical symptoms are paroxysmal wheezing, cough, and stridor. Asthma can occur suddenly, lasting from minutes to hours or even days, and may resolve on its own or with medication. There is often a history of previous episodes. Attacks can be triggered by various factors such as inhaling or exposure to allergens, upper respiratory infections, exercise, or emotional stress. During an asthma attack, the lungs may appear hyperinflated, with prolonged expiratory sounds and audible wheezing. Severe asthma patients often exhibit dysphoria, marked use of accessory respiratory muscles, increased respiratory and heart rates, and pulsus paradoxus. The presence of paradoxical chest and abdominal movements and cyanosis indicates a critical condition.
Based on typical clinical symptoms and medical history, including recurrent episodes of panting, chest tightness, cough, and wheezing sounds in both lungs, with identifiable triggers, symptoms that can be relieved by bronchodilators or spontaneously, and after excluding other diseases, a preliminary diagnosis can be made. Pulmonary function tests showing reduced FEV1 indicate airflow obstruction; a bronchial dilation test, where FEV1 increases by 15% after inhaling bronchodilators, is considered positive and can serve as a diagnostic basis for asthma. A bronchial provocation test showing a decrease in FEV1 or PEF by more than 20% compared to pre-medication levels indicates increased airway reactivity.
Additionally, intradermal tests, prick tests, or in vitro measurements of serum-specific IgE are commonly used to detect and identify allergens, though these methods have certain limitations. Bronchial provocation tests are particularly significant for diagnosing occupational asthma.
bubble_chart Treatment Measures
Avoidance of specific allergens and possible triggers is a fundamental principle of treatment. Conventional treatments include the use of anti-inflammatory and bronchodilator medications.
①Glucocorticoids are currently the first-line drugs for asthma treatment. They downregulate the production of pro-inflammatory factors, inhibit the synthesis and release of Th2 cytokines, suppress eosinophil proliferation and activation, inhibit gene transcription, and induce eosinophil apoptosis, thereby reducing airway inflammation. They can be administered systemically (e.g., methylprednisolone, hydrocortisone, or prednisone, intravenously or orally) or via inhaled glucocorticoid aerosols such as beclomethasone dipropionate (Clomethasone Dipropionate, Beclovent) or budesonide (Budesonide, Pulmicort).
②β2-agonists, such as salbutamol (albuterol, Ventolin), terbutaline (Bricanyl), and fenoterol, rapidly dilate the bronchi and relieve bronchospasm upon inhalation.
③Mast cell stabilizers like disodium cromoglycate, leukotriene receptor antagonists such as montelukast (Singulair), and antihistamines like ketotifen also have therapeutic effects.
④Theophylline derivatives, which inhibit phosphodiesterase and thus act as bronchodilators, are still widely used in China, including short-acting aminophylline and sustained-release theophylline preparations.
Immunotherapy plays a significant role in asthma treatment. For steroid-dependent or steroid-resistant asthma, immunosuppressants such as methotrexate, cyclosporine, triacetyloleandomycin (TAO), and gold preparations may be used. To enhance non-specific immunity or correct immune deficiencies, immunomodulators or immune enhancers like thymosin, transfer factor, or bacterial vaccines can be administered.
Allergen-specific immunotherapy (SIT) is a targeted treatment for asthma, particularly suitable for patients with identified and unavoidable allergens and mild-to-moderate chronic asthma (grade I). It can reduce symptom severity, with better efficacy observed in younger and pediatric patients. However, the widespread use of SIT is limited due to mixed opinions on its effectiveness, prolonged treatment duration, slow onset of action, and the risk of severe allergic reactions. Between 1997 and 1998, the WHO and the European Academy of Allergy and Clinical Immunology issued recommendations for SIT in asthma patients: a. SIT is ineffective for those with multiple allergens or non-allergic triggers. b. Efficacy is better in younger patients than in the elderly. c. SIT injections must be administered during asymptomatic periods. d. Patients should have an FEV1 ≥70% of predicted. e. SIT is well-suited for asthma triggered by Mongolian snakegourd root. f. It may be considered for patients allergic to animals who refuse to give up pet ownership. g. SIT is applicable for allergies to Alternaria and Cladosporium molds. Additionally, allergen extracts must be standardized, and desensitization therapy is not recommended for patients with multiple allergen sensitivities.
Bronchial asthma should be differentiated from wheezing bronchitis, cardiac asthma caused by left heart failure, dyspnea due to airway obstruction from large airway tumors, pulmonary eosinophilic infiltration, and wheezing caused by bronchiolitis in children.
