| Both chronic obstructive pulmonary disease and asthma are common chronic airway diseases.In China,the prevalence of COPD among people over 40 years old is13.6%-13.7%.The prevalence of asthma among people over 20 years old is 4.2%.The burden of these two diseases is very heavy,and frequent acute exacerbations can cause obstacles to work and life,and affect the development of family and society.Inhaled bronchodilators,inhaled corticosteroids and other inhaled drugs are the most important drugs for the treatment of chronic airway diseases,and they are also the preferred treatment options of various guidelines worldwide.Inhaled drugs have the characteristics of rapid action and small adverse reactions,and have unique advantages in the treatment of lung diseases.However,the therapeutic effect of such drugs depends on the correct operation of the patient and the application of the appropriate inhalation method.Especially dry powder inhalers,this type of dosage form requires the patient to actively inhale as the driving force to excite the drug from the device and depolymerize with the carrier that wraps the drug,inhaling into the lungs to achieve a therapeutic effect.Therefore,the correct operation of the drug and the proper inhalation flow rate are of great significance to the role of the drug.In order to understand the current clinical correctness of the use of dry powder inhalers,we first conducted a cross-sectional survey,surveying 85 patients who had previously used dry powder inhalers,drug handling techniques and peak inspiratory flow rates.Although foreign literatures have recommended the minimum and appropriate peak inspiratory flow rate for different dry powder inhalants,the evaluation of the patient's peak inspiratory flow rate in China's mainland has not been reported.We found that there are serious problems with the use of dry powder inhalers.The overall incidence of patient operation errors was 65.9%,and the incidence of inappropriate daily inspiratory flow rate was 38.8%.Old age is a risk factor for inappropriate inspiratory flow rate(OR?=?1.06,95% CI 1.01–1.12).Combined respiratory disease is also a risk factor for inappropriate inspiratory flow rate(OR?=?6.59,95% CI 1.14–38.15).High education level is a protective factor for operating errors.The higher the education level,the lower the possibility of operating errors(OR?=?0.63,95% CI 0.40–0.99).Although the peak inspiratory flow rate is an important parameter that affects the pulmonary deposition of dry powder inhalers,other inspiratorry parameters,including inspiratory volume,inspiratory acceleration,inspiratory time can also affect the lung deposition of drugs.At present,for the inhalation method of dry powder inhalers,the guide recommends strong and deep inhalation,but lacks quantitative standards,and cannot provide objective and scientific training methods for patients in medication guidance.Therefore,in this study,we explored the law of inhalation parameters on the lung deposition of dry powder inhalants,so as to provide objective standards for future patient inhalation training.In Chapter 2,we introduced an inhalation training device developed by ourselves.The instrument can simulate the resistance of the inhalation device,and can record the patient's inhalation curve in real time,and then collect the corresponding inhalation parameters.This provides a basis for our follow-up study on the influence of inhalation parameters on the pulmonary deposition of dry powder inhalers.In Chapter 3,we recorded the inspiratory curves of 32 patients,collected inspiratory parameters and statistical analysis,and found that there are significant differences in the inspiratory parameters of patients under different disease conditions.The peak inspiratory flow rate of COPD patients was significantly lower than that of asthma patients(P=0.003).The inspiratory volume of COPD patients was significantly lower than that of asthma patients(P=0.001).The baseline time was significantly shorter than that of asthma patients(P=0.003).We also found that the patient's peak respiratory flow rate(PEF)is an independent factor that affects the peak inspiratory flow rate and inspiratory acceleration,and the forced expiratory volume in the first second(FEV1)is an independent factor that affects the inspiratory volume and total inspiratory time.This suggests that our patients with low lung function parameters may also have low inspiratory parameters.At the same time,we found that the inspiratory volume we tested and inspiratory capacity tested by lung function in COPD patients were 1.4±0.5L and1.6±0.7L,respectively.In the Pharmacopoeia,there are two test for dry powder inhalers(the uniformity test of the delivered dose and the determination of the aerodynamic characteristics of fine particles).The inspiratory volume for both experiments is 4L.It is suggested that the simulated volume of the inhalation powder aerosol test in the Pharmacopoeia cannot reflect the actual volume of the patient's inhalation.In Chapter 4,we further analyzed the pulmonary function data,and studied the pulmonary function parameters as the appropriate diagnostic accuracy and diagnostic cutoff value for the diagnosis of peak inspiratory flow rate.We found that PEF,FEV1,FEV1/expected value and inspiratory capacity were all statistically significant(P<0.05)in predicting suboptimal peak inspiratory flow rate in patients using Handihaler.According to the calculation of the Youden index,the diagnostic cut-off value of FEV1/pred value is46.5%,the diagnostic cut-off value of PEF is 2.7L/min,the diagnostic cut-off value of FEV1 is 1.1L,and the diagnostic cut-off value of IC is 1.7L.When patient value is lower than the above value,the patient may have suboptimal peak inspiratory flow rate of Handihaler.Among them,PEF has the largest area under the curve(AUC)and the highest prediction accuracy(sensitivity is 86.2%,specificity is 100%).In Chapter 5,we use in vivo and in vitro correlation experiments to study the laws between inspiratory parameters and lung deposition.Input 12 inhalation curves from the patient into the breathing simulator and connect to the step-by-step impactor.Through quantitative transfer and HPLC analysis,the total emitted dose,fine particle dose,and average dose of each inhalation curve corresponding to the drug can be obtained.Through single-factor and multi-factor analysis,we found that the inhalation volume has a significant linear relationship with the fine particles dose(P=0.003).The larger the inhalation volume,the larger the dose of fine particles.The fine particles are the particles that exert the drug effect and are also an important parameter in the in vitro deposition experiment.Therefore,the inspiratory volume may have a significant impact on the lung deposition.The peak inspiratory flow rate,inspiratory volume,and peak time have a significant linear relationship with the average aerodynamic particle size,and multiple regressions have found independent risk factors that affect the average aerodynamic particle size at the inspiratory peak flow rate(P<0.001).Therefore,the peak inspiratory flow rate may affect the average aerodynamic particle size of the drug.Through experiments,we found that the factors affecting lung deposition may be complex and comprehensive.For Handihaler,it is recommended that patients inhale the maximum inspiratory volume and reach an appropriate inspiratory flow rate of 30l/min.Breathing training device can provide a visual and quantifiable tool for patient inhalation training.The clinical use of dry powder inhaler is still not standardized enough,and it is necessary to include pharmacists and multiple parties to improve the standardization of medication.Through the exploration of key inspiratory parameters,we found that the inspiratory volume has a significant effect on the dose of fine particles.This reminds us that when we train patients to inhale dry powder inhalants,we should not only pay attention to whether the peak inspiratory flow rate is appropriate,but also instruct patients to pay attention to the inhaled volume and inhale the medicine more fully.The inhalation training device can assist the pharmacist to personalize the inhalation method of the patient.In addition,the inhalation method of patients is very different from the inhalation method simulated by the pharmacopoeia for inhaler quality control.It is difficult for patients with COPD to reach the inhalation volume of 4L,which should be paid attention to in the research and development of inhalation powder. |
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