Efficacy and Safety of Yiqi Wenyang Sanhan Formula Combined With Acupoint Application in Patients With Combined Allergic Rhinitis and Asthma Syndrome During Remission and Yang-Deficiency Syndrome: Study Protocol for a Double-Blind Randomized Controlled Trial
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 188
- 主要终点
- Control of Allergic Rhinitis and Asthma Test (CARAT) scores
研究概览
简要总结
Allergic rhinitis-asthma syndrome is a clinical comorbid condition involving both upper and lower airway allergic inflammation, reflecting the concept of "one airway, one inflammatory response." Epidemiological studies have demonstrated a strong coexistence between allergic rhinitis and asthma: allergic rhinitis is present in a substantial proportion of patients with asthma, while some patients with allergic rhinitis may further develop concomitant asthma. Clinically, the disease is characterized by recurrent and fluctuating episodes, which are often associated with seasonal or persistent allergen exposure. In terms of symptomatology, upper airway manifestations mainly include nasal itching, paroxysmal sneezing, watery rhinorrhea, and nasal obstruction, whereas lower airway manifestations are primarily recurrent wheezing, shortness of breath, chest tightness, and cough. When these two conditions coexist, they not only increase the overall symptom burden but also further impair patients' quality of life and complicate disease control.
During the remission stage, patients may exhibit alleviation of nasal and lower airway symptoms and may even enter a relatively "asymptomatic" state; however, this does not necessarily indicate complete resolution of airway inflammation. The Global Initiative for Asthma has emphasized that even in patients with only intermittent or infrequent symptoms, persistent airway inflammation may still be present. Therefore, the central goal of management during remission is not merely to wait for recurrence, but to reduce the risks of acute exacerbation and disease progression through standardized long-term intervention. Specifically, inhaled corticosteroid (ICS)-containing regimens should be maintained as the cornerstone of asthma control during remission, and sole reliance on short-acting β2-agonists should be avoided. Meanwhile, in patients with concomitant allergic rhinitis, nasal management should be carried out simultaneously, with intranasal corticosteroids particularly recommended. In addition, attention should be paid to allergen exposure control, correct use of inhalation devices, treatment adherence, and the assessment of comorbidities. Existing systematic reviews also suggest that conventional treatment for rhinitis may improve quality of life in patients with this comorbidity to a certain extent and may have favorable effects on some objective asthma outcomes, although its impact on overall asthma control remains somewhat heterogeneous.
Precisely because patients with allergic rhinitis-asthma syndrome remain at risk of persistent inflammation, constitutional imbalance, and recurrent attacks during remission, traditional Chinese medicine (TCM) has considerable potential for intervention at this stage. TCM emphasizes the principle of "treating disease before its onset," namely, preventing illness before it arises and preventing progression once it has occurred. Its strengths lie not only in symptom control during the active phase, but also in the regulation of the overall bodily state, constitution-based differentiation, and the proactive management of recurrence risk during remission. The International Clinical Practice Guideline for Allergic Rhinitis in TCM, issued by the World Federation of Chinese Medicine Societies in 2024, has incorporated standardized frameworks for internal therapies, external therapies, constitution identification and regulation strategies, as well as preventive and nursing measures, highlighting the unique role of TCM in the long-term management of allergic airway diseases. At the same time, existing systematic reviews and narrative reviews suggest that interventions such as acupuncture, acupoint application, and Chinese herbal medicine may have certain potential in improving rhinitis symptoms, enhancing quality of life, and reducing recurrence rates in some patients; however, the overall quality of evidence and the consistency of findings still require further improvement.
Based on the above considerations, the present study shifts the focus forward to the remission stage of allergic rhinitis-asthma syndrome, targeting this critical period in which symptoms may be temporarily alleviated but inflammation persists, and clinical stability coexists with an ongoing risk of recurrence. By using the Yiqi Wenyang Sanhan Formula combined with acupoint application therapy, this study attempts to explore the clinical value and practical significance of TCM intervention in the long-term management of this condition. Unlike research approaches that focus exclusively on the control of acute exacerbations, the present study places greater emphasis on the systematic evaluation of recurrence prevention, interruption of disease progression, and optimization of the overall patient condition, with the aim of providing evidence for whole-course management strategies more consistent with the characteristics of chronic allergic airway diseases.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 16 Years 至 79 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Fulfilled the western medicine diagnostic criteria for CARAS.
- •Had clearly defined seasonal attack characteristics and were diagnosed with CARAS of the yang-deficiency syndrome type during the remission stage.
- •Were aged 16-79 years.
- •Were informed of the study details and provided written informed consent.
- •Had a general physical condition and mental status sufficient to ensure the objective and accurate reporting of symptom characteristics and treatment responses.
排除标准
- •A diagnosis of vasomotor rhinitis or non-allergic rhinitis with eosinophilia syndrome.
- •Known or suspected allergy to any component of the study medication, or any contraindication to the study medication or glucocorticoid therapy.
- •Current participation in another drug trial, or concomitant use of other oral traditional Chinese medicines or external medicinal patches.
- •The presence of severe primary diseases affecting major organs or systems, including the cardiovascular, hepatic, renal, or hematopoietic systems, or the presence of a psychiatric disorder.
- •Pregnancy or lactation.
- •Inability to clearly provide syndrome-related information.
研究组 & 干预措施
treatment group received the Yiqi Wenyang Sanhan Formula combined with acupoint application
The treatment group received the Yiqi Wenyang Sanhan Formula (the detailed composition is provided in Table 1; 200 mL per sachet), which was prepared by the Department of Traditional Chinese Medicine Preparations, Beijing Daxing District Hospital of Integrated Traditional Chinese and Western Medicine. The regimen consisted of oral administration twice daily, once in the morning and once in the evening after meals, for 4 consecutive weeks. The herbal formula was initiated 1 month before the anticipated onset of each patient's disease cycle, with the aim of achieving preventive and therapeutic effects during the remission stage.
For acupoint application therapy, the herbal materials were ground into a fine powder and mixed with ginger juice to form a paste, which was then applied to the following acupoints (Figure 2): Tiantu (RN22), Gaohuang (BL43), Feishu (BL13), Shenshu (BL23), and Guanyuan (RN4).
干预措施: Yiqi Wenyang Sanhan Formula Combined with Acupoint Application (Drug)
control group received a placebo of Yiqi Wenyang Sanhan Formula and acupoint application
The control group received a placebo matched to the Yiqi Wenyang Sanhan Formula in appearance and primary color, which was prepared by the Preparation Room of Beijing Daxing District Hospital of Integrated Traditional Chinese and Western Medicine. The placebo was administered in the same manner as in the treatment group, i.e., orally twice daily, once in the morning and once in the evening after meals, for 4 consecutive weeks. The herbal formula was initiated 1 month before the anticipated onset of each patient's disease cycle, with the aim of achieving preventive and therapeutic effects during the remission stage.
The control group received a placebo patch matched to the acupoint patch in appearance and primary color. Acupoint application was initiated 1 month before the anticipated onset of each patient's disease cycle and was used in combination with the herbal formula. The patches were applied once every other day, with each application lasting 4-6 h.
干预措施: placebo of Yiqi Wenyang Sanhan Formula combined with acupoint application (Drug)
结局指标
主要结局
Control of Allergic Rhinitis and Asthma Test (CARAT) scores
时间窗: up to 4 weeks
The CARAT is the first and, to date, the only instrument capable of simultaneously assessing disease control in both the upper and lower airways, in line with the recommendations of the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines. This brief 10-item questionnaire covers upper and lower airway symptoms, sleep disturbance, activity limitation, and the need for treatment escalation over the preceding 4 weeks, and is used to quantify the level of control of allergic rhinitis and asthma. Control of Allergic Rhinitis and Asthma Test (CARAT), total score range 0 to 30; higher scores indicate better control of allergic rhinitis and asthma (better outcome), whereas lower scores indicate poorer control (worse outcome).
pulmonary function parameters：Forced Vital Capacity (FVC)
时间窗: up to 4 weeks
Forced Vital Capacity (FVC): the maximal volume of air forcibly exhaled after full inspiration. Unit: Litres (L)
pulmonary function parameters：FVC%
时间窗: up to 4 weeks
FVC%: FVC expressed as a percentage of the predicted value derived from reference equations. This metric supports longitudinal assessment of ventilatory capacity relative to expected normal values. Unit: Percent (%) of predicted value. Usually, a predicted value of ≥ 80% is considered within the normal range. A value below 80% suggests the possibility of restrictive ventilatory dysfunction.
pulmonary function parameters：FEV1%
时间窗: up to 4 weeks
FEV1%: In the context of allergic rhinitis-asthma syndrome, FEV1%pred is used to quantify the degree of airflow limitation. Unit: Percent (%) of predicted value. Usually, a predicted value of ≥ 80% is considered within the normal range. A value below 80% suggests the possibility of restrictive ventilatory dysfunction.
pulmonary function parameters：FEV1/FVC ratio
时间窗: up to 4 weeks
FEV1/FVC ratio: In asthma-related assessment, a reduced FEV1/FVC ratio supports the presence of airflow limitation. Unit: Ratio (no unit) or Percent (%). The lower limit of normal for this value varies with age. For healthy young adults, it is typically \> 0.75, or 75%. In clinical practice, an age-adjusted lower limit of normal is more commonly used, with \< 0.70 serving as a criterion supporting the presence of persistent airflow limitation.
pulmonary function parameters：Peak Expiratory Flow (PEF)
时间窗: up to 4 weeks
Peak Expiratory Flow (PEF): the maximum expiratory flow achieved during a forceful expiration from full lung inflation. Unit: Litres per minute (L/min) or Litres per second (L/s). According to the commonly used zones defined by the NHLBI and the American Lung Association, 80-100% of the personal best is classified as the green zone, 50-79% as the yellow zone, and \<50% as the red zone.
quality-of-life (QL) measures：Rhinasthma
时间窗: up to 4 weeks
Rhinasthma: a disease-specific health-related quality-of-life questionnaire for patients with rhinitis and/or asthma. The original instrument contains 30 items across three domains-Upper Airways, Lower Airways, and Respiratory Allergy Impact-with an additional global summary score. Items are rated on a 5-point Likert scale, and domain scores are typically transformed to a 0-100 scale, with higher scores indicating worse quality of life.
quality-of-life (QL) measures：EQ-5D-5L
时间窗: up to 4 weeks
EQ-5D-5L: The EQ-5D-5L descriptive system is a generic measure of health-related quality of life comprising 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 severity levels (Level 1 to Level 5): no problems, slight problems, moderate problems, severe problems, and extreme problems/unable to, as applicable to the dimension. Responses define a 5-digit health-state profile, which can be converted into a single health utility index using an appropriate country- or region-specific EQ-5D-5L value set. Unit of measure: utility score (unitless).
次要结局
- symptom scoring scale of Traditional Chinese medicine(up to 4 weeks)