1. Definition and mechanism
1.1 Phenomenon.
The onset phase is characterized by “reversible”, airway-derived dyspnea.
The remission period is characterized by susceptibility or hypersensitivity to a variety of complex specific or nonspecific in vivo and exogenous factors.
1.2 Nature.
The remission phase manifests as chronic nonspecific inflammation of the airway involving a variety of airway intrinsic cells (native cells) and/or inflammatory infiltrating cells and their associated array of cytokines.
As a metaplasia, the above-mentioned localized lesions of the airways have received widespread attention. What is easily overlooked is that metaplasia is more of a systemic disease because: (i) asthma is often associated with allergic rhinitis, eczema, and cushings fever. ② Asthmatic patients often show active eosinophil function and elevated serum IgE. ③Airways and skin often have the same allergens. ④Patients with severe asthma have significant effects with the addition of systemic medications (leukotriene blockers IgE monoclonal antibodies, glucocorticoids). ⑤ The asthma exacerbation period shows an overreaction to mild stress or stimulation.
2 .Pathological changes
2.1 Basic pathology.
Mucosal inflammatory edema : reversible
Smooth muscle spasm: reversible
Mucus gland hyperplasia Non-reversible
2.2 Special pathology.
① Airway reconstruction (Reconstruction or Restructure) manifests as smooth muscle hyperplasia, hypertrophy, and fibrous tissue hyperplasia.
② Systemic Inflammatory Response Syndrome (SIRS): when an asthma attack occurs.
3. Diagnosis
3.1 Preliminary diagnosis (suspected diagnosis): ① Patients with asthma often have a personal history or family history of allergic rhinitis, eczema, or kwashiorkor fever; ② Recurrent coughing and wheezing episodes. Triggers are often allergens, infections, exercise, etc. (common in those ≥3 years of age or older). ③ Recurrent upper respiratory tract infections are highly likely to develop into the lungs causing cough, lasting >10 days each time, with antibiotic insensitivity and good efficacy to airway dilators, corticosteroids, and
3.2 Grading and grading: ① Episodes: grading (mild, moderate, severe) grading is based on textbooks listing many signs and symptoms, which can be roughly corresponded to the following levels of performance.
(a) Pure airway manifestations: respiratory symptoms such as cough, wheezing or croup with bronchospasm only; with or without hypoxemia.
With supplementary respiratory muscles breathing: on top of the above symptoms appear such as trigeminal signs, nodding breathing, nasal agitation, etc., in older children or adults presenting in a specific position; commonly accompanied by hypoxemia. Mental symptoms are predominantly excitatory, such as irritability and temper tantrums.
Accompanied by CO2 retention (type II respiratory failure) or impaired consciousness, there must be obvious hypoxemia.
②Relief period: grading
Based on the number of asthma attacks per unit time (monthly, weekly, daily) and the number of nocturnal attacks, which integrates the degree of airway hyperresponsiveness and inflammatory response, and is the basis for early treatment plan development.
4. Treatment
4.1 Rationale.
The attack period: restore lung function and save life as soon as possible (inhalation with short-acting airway dilators is the mainstay, with systemic hormones and other supportive therapies such as oxygenation if necessary).
Remission period: reduce (preferably eliminate) non-specific inflammation of the airway, prevent its recurrence (local hormone inhalation) mainly; and restore normal lung function as far as possible (add long-acting airway dilators); prevent irreversible airway lesions from arising. Namely: for non-specific inflammatory responses: glucocorticoids, IgE blockers (IgE monoclonal antibodies), classical cytokine blockers (leukotriene blockers, PDGF blockers and IL-4 monoclonal antibodies). For bronchial smooth muscle spasm: bronchodilators, beta receptor stimulants, or M receptor blockers. For mucus gland hyperplasia and hypertrophy: cholinergic blockers, glucocorticoids. Against airway remodeling: an important cause of CDPP production and difficulty in asthma control, its occurrence can be prevented by early and rational treatment.
Minimal (preferably no) medication side effects.
Minimal cost of treatment.
4.2 Pharmacology of asthma treatment.
4.2.1 Glucocorticoid inhalation therapy.
Research history.
Glucocorticoids were found to have anti-asthmatic effects in the 1950S era, and to this day, they remain the most effective anti-asthmatic inflammatory drug for most patients with moderate to severe asthma, but long-term systemic application has serious side effects.
In 1960S, glucocorticoids (hydrocortisone, prednisolone, etc.) were tried by nebulized inhalation, which was not superior to systemic medication due to the backward nebulization technology and the poor lipid solubility, permeability and activity of the drugs, poor selectivity, and the amount of inhaled drugs reaching the oral dosage before being effective.
In the mid-1970s, beclomethasone dipropionate (BDP) was introduced to create a new era of asthma treatment. In the 80s and 90s, the introduction of butalbital (Pulmicort, or PUL) and fluticasone hydrochloride (Fosolone, or FP) consolidated the status of local hormone therapy.
Pharmacodynamics of glucocorticoid inhalers.
Chronic inflammation of the airways is the underlying cause of airway hyperresponsiveness, and glucocorticoids work by effectively reducing or eliminating this inflammation; inhaled BDP is effective for 1 week, with peak effects in 3 months.
Inhibition of allergen-induced biphasic asthma response: Inhalation of allergens for specific bronchial provocation tests can produce tachyphylaxis and delayed-onset asthma responses. The tachyphylaxis response is characteristic of the acute phase of asthma (IgE-related or type I allergic reaction); the delayed-onset response is similar to the chronic phase of asthma (chronic non-specific inflammation of the airways). Inhalation of glucocorticoids for 1 week has an inhibitory effect on both, thus significantly improving pulmonary ventilation and clinical symptoms, as evidenced by the reduction and disappearance of asthma symptoms and improvement in FEV1 or PEF.
Common types of glucocorticoid inhalers and their differences.
Beclomethasone dipropionate, pramipexole and corticosteroid propionate are the most commonly used inhaled hormones in clinical practice. The differences in their efficacy and side effects depend on the corresponding lipid solubility, receptor affinity and first-pass effect; the higher the lipid solubility, the easier it is for the drug to cross the cell membrane and produce stronger efficacy with the glucocorticoid receptors in the nucleus; the stronger the receptor affinity, the stronger and longer the duration of the drug’s efficacy; the higher the first-pass effect, the more the hormone molecule The higher the first-pass effect, the more the hormone molecules are destroyed by the liver, and the less systemic side effects are produced.
The lowest first-pass effect and anti-inflammatory effect is BPP, and the highest is FP. Therefore, FP is popular as the most powerful anti-inflammatory drug with relatively few side effects, especially for those who require large amounts of medication (>800ug/d).
Side effects of topical inhaled hormones.
By improving the drug dosage form (aerosol → powder), increasing the lipid solubility and improving the inhalation method, the side effects will be greatly reduced, and the systemic side effects of inhaled hormones have been significantly lower than those of systemic drugs under the same efficacy. The systemic side effects of inhaled hormone have been significantly lower than systemic side effects with the same efficacy.
Systemic side effects: The main side effect is the suppression of hypothalamic-pituitary-adrenal axis (HPA), which may cause difficulties in stopping the drug in serious cases.
Local side effects.
Fungal mouth, pharynx and laryngitis (1-20%) are seen in those who do not rinse their mouths after inhalation or do not rinse their mouths in time, do not use a storage fog canister, have improper inhalation techniques, have a long course of treatment and have a high dosage of poor health.
Hoarseness: vocal cord contraction function is affected by the drug, there is no better way to prevent and control.
Small hematoma in the oral cavity: it is caused by submucosal capillary congestion and bleeding.
Facial irritation: caused by the odor of the projectile or the drug.
The correct inhalation method is the basic prerequisite to ensure the efficacy of the treatment.
Metered Dose Inhalers (MDI) are two or three phase aerosols, with gas (Freon, etc.) as a booster to throw out an equal amount of drug, and need to ensure as much as possible airway straightening, synchronization of inhalation and spraying and sufficient drug retention time (10S), children <4~5 years old should use a storage canister; the drug airway accumulation rate of MDI can reach 10%, exhalation 5%, oral + pharyngeal deposition >80 It is the main cause of systemic side effects, and the addition of a fog storage tank can reduce or eliminate this part of the side effects.
Dry viscous inhalation preparations: such as pramipexole and sulforaphane, require faster inhalation to inhale dry powder drugs into the airway, and MDI aerosol should be used in young children (<5~6 years old) or those who cannot inhale correctly after training. The advantage is the high airway deposition of drugs (15-20%) deposited in the oropharynx, and its secretions can be easily removed by gargling.
Nebulizer inhalation: Electric nebulizer device (nebulized particles 5~7μm) is used to deliver the drug into the airway, the indications and principles are similar to MDI, for those with moderate or severe asthma or monthly relapses, this method should be used first to control relapses in the first 2-3 months of treatment, then gradually transition to MDI or dry powder formulations.
4 , 2.2 β-receptor stimulants.
According to the duration of action classified as: short-, medium- and long-acting drugs.
Short-acting (≤6hr), so butorphanol (Ventolin, Salbutamol).
Medium-acting (>6hr ≤10hr), such as terbutaline (Bolycanib).
The biggest advantage: fast onset of action. (inhalation takes effect within minutes) Strong bronchodilator effect (salbutamol is 1000 times more effective than aminophylline), adapted for use during asthma attacks.
Long-acting preparations (≥12hr), commonly used salmeterol (Sulmeterol), formoterol (Formeterol aka Antonek), the duration of action of about 12hr, to help prepare (Bambuterol Bambuterol or bambec) duration of action of 17 ~ 18hr, so the former is suitable for twice daily dosing, the latter is suitable for once a day, long-acting The bronchodilator effect of the long-acting preparation is weaker than that of the short-acting one, but still stronger than that of aminophylline. The greatest benefit of the long-acting formulations is that they help improve lung function and reduce the amount of hormone used.
Controlled-release theophylline such as sulforaphane can also be tried if the child is able to swallow the whole tablet.
Side effects and prevention of β-receptor stimulants – one is cardiovascular side effects: for pre-existing cardiac disorders or drug hypersensitivity, manifested as arrhythmias, myocardial ischemia, especially when combined with aminoglycosides, tachycardia is almost universal, the most obvious in the medium and short-acting, so in recent years, medium and short-acting preparations have been rarely used. The second is to aggravate airway inflammation to worsen asthma: from 1970 to 1980s, the increased mortality of asthma abroad was related to the long-term and regular use of medium- and short-acting airway dilator drugs during the same period, probably related to the neglect of glucocorticoid application, and it was even thought that short-acting agents promote the production of inflammatory mediators at the molecular level.
Although the anti-inflammatory effect of long-acting β-receptor stimulants has been observed in animal studies in vivo or in isolated specimens, this anti-inflammatory effect is negligible compared to that of corticosteroids and is almost therapeutically meaningless, and its presence, if any, is not a pharmacological reason for the use of long-acting agents in asthma treatment; on the contrary, it has been suggested that long-term application of long-acting agents slightly increases airway inflammation.
β-receptor downregulation, due to long-term application of β-agonists (especially medium- and short-acting systems) will phosphorylate and internalize β-receptors and appear to diminish or disappear the airway dilating effect, which occurs in 1-2 weeks of common use, but can be restored after a week of discontinuation of the drug.
Other, bone and iliac muscle tremor, paradoxical bronchospasm, elevated blood sugar, etc.
5.About the efficacy of traditional medicine on asthma
Traditional medicine, especially Chinese medicine, has been evaluated in various countries and is by and large negatively evaluated, so care should be taken in treatment. At least not as a substitute for topical hormones used in anti-inflammatory treatment.