Bronchial asthma is an inflammatory airway disease with airway smooth muscle dysfunction, manifested mainly by increased basal contractile tone of the ASM and excessive and premature contractile responses upon exposure to various stimuli, i.e., airway hyperresponsiveness (AHR). Modern treatment of asthma emphasizes both airway inflammation and smooth muscle spasm, i.e. inhaled glucocorticoids (ICS) to suppress airway inflammation and bronchodilators (BD) to relax ASM. β2 agonists are currently the first-line BDs for diastolic ASM and bronchospasm relief, and can be broadly classified into LABA and SABA. LABA has stronger bronchodilatory activity and longer duration of action than SABA. In 2003, the Global Initiative for the Prevention and Control of Bronchial Asthma (GINA) recommended ICS combined with LABA as the first treatment option for moderate-to-severe asthma, and the 2006 revised GINA and China’s asthma control guidelines still recommend ICS as the first treatment option for uncontrolled asthma. The combination of ICS/LABA has been used in clinical practice for nearly a decade and has been shown to be effective in relieving asthma symptoms, improving lung function, and improving the quality of life of patients with asthma, and has been shown in some studies to reduce the frequency of acute exacerbations. It can be said that the introduction and promotion of ICS/LABA combination therapy is a revolutionary development in the field of asthma treatment in the past 10 years, which has contributed to the overall improvement of asthma control. However, the controversy surrounding LABA has never subsided since its inception, and the combination of ICS/LABA is clearly superior to LABA alone, but certain questions remain, such as (1) the interaction between ICS and LABA: it is more recognized that ICS and LABA have synergistic effects in terms of efficacy, but can ICS avoid or mitigate the side effects of LABA? Although some studies have shown that ICS has a certain degree of protective effect on LABA, there is a lack of conclusive medical evidence and its molecular mechanism has not been fully elucidated; (2) although some studies have shown that continuous use of high doses of ICS/LABA helps maintain stable asthma control, it has been clinically found that some patients gradually experience decreased efficacy and poor asthma control after receiving ICS/LABA for 6 months or 1 year. Therefore, Batemam suggested that the maintenance of low-dose ICS/LABA should be continued during the step-down phase, which implies a longer course of combination therapy, and the safety issues are more worrying; (3) Most data show that LABA alone aggravates airway inflammation. . The Lundbak study found negative airway reactivity in about 1/3 of asthma patients treated with the LCS/LABA combination for three years, which is better than ICS alone but at least indicates that for a long enough course of treatment, most asthma patients do not clear airway inflammation and do not eliminate airway hyperresponsiveness. A study by the author in 2004 also confirmed that one year of salmeterol/fluticasone treatment resulted in negative airway reactivity in less than 1 in 10 patients. Given the profound lessons learned from the abuse of SABA in the 1970s to 1980s, the respiratory community has been concerned about the safety of LABA, and the 2004 U.S. SMART clinical study found that salmeterol was associated with an increased risk of asthma-related death in African Americans, leading to the early termination of the trial. The U.S. FDA issued safety warnings for all LABAs in November 2005 and May 2006. In particular, on February 18, 2010, in view of the many unclarified issues in the use of LCS and LABA and the overuse of LABA that has now been exposed in the clinical setting, and based on the Salmeterol Multicenter Asthma Study clinical trial, the Salmeterol National Surveillance Study (SNS, enrolling 25,180 patients) and the FDA-sponsored implementation in 2008 of a systematic evaluation containing 110 The FDA issued another announcement on the safety of LABA on February 18, 2010, based on a systematic evaluation of 110 clinical trials conducted under the auspices of the FDA in 2008 (enrolling 60,954 patients), the main points of which were: The FDA affirmed that LABA should never be used alone for the treatment of asthma in adults. Manufacturers are required to include this warning on the labeling of such drug products, as well as take other steps to reduce the overuse of such drugs. These new requirements are based on FDA data from a series of clinical trials showing that LABA use is associated with an increased risk of severe worsening of asthma symptoms, hospitalization, and even death in some patients in both children and adults. These include stand-alone LABA formulations such as Schlitzel (Serevent, salmeterol) and Foradil (formoterol), as well as combinations with inhaled glucocorticoids such as Advair (salmeterol/fluticasone) and Symbicort (budesonide/formoterol). The FDA requires that product labeling reflect the following information: LABA should not be used if other asthma controller medications, such as ICS, are not being used; LABA should only be used in combination with other controller medications and not alone; LABA should only be used long-term in patients who do not achieve adequate control with other asthma controller medications; LABA treatment should be the shortest course of therapy to achieve asthma symptom control; and LABA therapy should be used to achieve the shortest course of asthma symptom control and should be discontinued whenever possible once asthma control has been achieved. Patients should be maintained with other controller medications. Pediatric and adolescent patients requiring treatment with both LABA and ICS should be treated with a combination formulation containing both ICS and LABA to ensure adherence to therapy. Badrul Chowdhury, MD, PhD, chief of the Division of Cardiopulmonary and Allergic Diseases in the FDA’s Drug Evaluation Study, commented: Although LABAs have played an important role in helping some patients control their symptoms, after reviewing the available clinical trial data, because LABAs are associated with an increased risk of acute asthma exacerbations, hospitalization, and death, we believe that whenever possible (whenever possible), the use of LABAs should be limited. Dr. Dianne Murphy, director of the FDA’s Office of Pediatric Therapeutics, also noted that the high risk of hospitalization and poor control is particularly alarming for pediatric asthma. Parents should be aware that LABAs should never be used alone. The FDA has also urged LABA manufacturers to conduct additional studies to further evaluate the safety of combining LABAs with ICS. The FDA’s latest announcement has caused a stir in the community and a great deal of reaction in the respiratory community due to the spin or misinterpretation by some domestic and international media. Some people questioned whether the basis was adequate, too harsh or hasty. The FDA’s announcement does not endorse the use of LABA alone, but rather the combination of ICS/LABA, which is in line with GINA’s recommendation, and is aimed at asthma rather than COPD. In fact, excessive, stand-alone use of LABA is mainly seen in the US and a few EU countries; in our country, there is no salmeterol single agent formulation and formoterol (Oxydub, Antonek) is largely no longer recommended. Therefore, for LABA and ICS/LABA, there is no question of “to be or not to be”, and the so-called “withdrawal” is a pseudo-proposition. Nevertheless, this latest announcement reveals the FDA’s serious concern about the safety of LABAs and its determination to restrict their overuse, and its language (should never; whenever possible) is unusually harsh. As the most stringent drug regulatory agency in the world, the FDA’s scientific and rigorous attitude, and the principle of safety over efficacy of drugs, have always been praised by the world, and ICS/LABA has been marketed in China for nearly 10 years, but we have never done any serious observation and analysis on its safety? ICS/LABA application in China presents a clear polarization phenomenon. On the one hand, ICS/LABA drugs are not available in the majority of primary care institutions, leaving many asthma patients without proper treatment; on the other hand, in large cities and hospitals, the fact that ICS/LABA pointers are extended to mild asthma, pediatric asthma, or that the course of treatment is too long is also unquestionable. Of course, the high risk of medications faced by asthma patients in China is not mainly from ICS/LABA, but the abuse of oral beta2 agonist preparations, systemic hormone abuse, and even informal medications are more serious medical and social problems. Several safety alerts from the FDA suggest the possibility of a reorientation of future asthma treatment strategies and a possible change in the current trend of over or pure reliance on ICS/LABA. On the other hand, we also need to On the other hand, we also need to be proactive and explore interventions to prevent, mitigate and offset the side effects of LABA or even replace LABA on the basis of the study of LABA safety.