Tiotropium (Spiriva) Found Beneficial In Early Stages of COPD

MedicalResearch.com Interview with:
Dr Prof Nanshan Zhong
, MD (Edin), FRCS (Edin), FRCP and
Pixin Ran PhD

National Center for Respiratory Diseases, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Diseases, the First Affiliated Hospital

MedicalResearch.com: What is the background for this study? What are the main findings?

Response:    According to the latest research, in 2015, 3.2 million people died from COPD globally, with an increase of 11.6% in mortality compared with that in 1990 (GBD 2015 Chronic Respiratory Disease Collaborators. Lancet Respir Med. 2017,5:691-706). COPD has now become the third leading cause of death worldwide and is estimated to become the disease with the seventh greatest burden worldwide in 2030. In China, the prevalence was 8.2% among people aged 40 years or greater, according to our epidemiological survey in 2007.

Importantly, current international guidelines have been mainly focusing on the management of moderate-to-severe COPD. However, among this patient cohort, the severely impaired lung function can only be reversed to a very limited extent despite the most potent treatment combinations. Patients with more advanced COPD are frequently associated with a significantly higher mortality and incidence of re-hospitalization and disability, which cause tremendous economic burden for both the families and the society. However, more than 70% of COPD patients are currently categorized as having stage I to early stage II COPD, most of whom have no or very few respiratory symptoms (Zhong NS, et al. Am J Respir Crit Care Med. 2007, 176:753-760; Mapel DW, et al. Int J COPD 2011; 6: 573−581). The vast majority of these patients would have the “COPD assessment Test” (CAT) score of 10 or lower (range: 0 to 40, with higher scores indicating more severe COPD). Admittedly, no medication has been recommended for this patient cohort according to the latest international guidelines. In real-world practice, these patients are almost neglected by physicians and have received virtually no medication. Nonetheless, the annual lung function decline rates among these patients are the most rapid among all COPD patients. (Bhatt SP, et al. Am J Respir Crit Care Med 2015; 191: A2433). An important clinical question has been raised regarding whether an intervention strategy targeting at early stages of COPD can possibly make the airflow limitation more reversible or prevent from further deterioration.

MedicalResearch.com: What have you found?

1.We have further reaffirmed the definition that COPD should be diagnosed NOT ONLY based on the respiratory symptoms plus impaired lung function (post-bronchodilator FEV1/FVC<0.7), but ALSO a history of long-term exposure to other critical risk factors (e.g. biomass fuel combustion, cigarette smoking, and/or poor air pollution) plus impaired lung function.

2.Two-year inhalation of tiotropium (18mcg q.d., a long-acting anti-cholinergic bronchodilator) significantly improved lung function (FEV1) by a mean of 157ml in patients with stage I — early stage II COPD. This improvement was much larger than those achieved in stage III -V COPD. Furthermore, tiotropium inhalation also improved the quality of life and significantly reduced the frequency of acute exacerbation of COPD with no major adverse events (e.g. cardiovascular events).

3.This is the first prospective study showing an amelioration of post-bronchodilator annual FEV1 decline rate after two years’ administration of tiotropium.

MedicalResearch.com: What should clinicians and patients take away from your report?

Response: We have shown that early-stage intervention of COPD with tiotropium effectively ameliorated and even partially reversed the airflow limitation, and may prevent from a further deterioration in the disease severity. Tiotropium inhalation also led to a significant improvement in patient’s quality of life.

For patients with a long-term history of exposure to risk factors, routine screening with spirometry is necessary. Once the diagnosis of COPD is confirmed, avoidance of the risk factors (e.g. smoking cessation) is imperative.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

1.A long-term follow-up investigation should be carried out to determine if the maintenance therapy with at least one category of medications is needed for early stage COPD. In fact, we have followed-up some of these patients for another 12 months after withdrawal of tiotropinum inhalation. We did notice a more rapid rate of decline in FEV1 during tiotropium withdrawal phase compared with the previous treatment phase (24 months). At the end of 12-month withdrawal, FEV1 in tiotropium group did not differ from that in placebo group (overlapped). This finding indicated that long-term maintenance therapy with tiotropium is needed.

2.We cannot exclude the possibility that there exist other medications which may be equally effective or better than tiotropium for the management of early-stage COPD. Further research that addresses this issue may be of value.

MedicalResearch.com: Is there anything else you would like to add?

Response: There has been a huge progress in the management of other common diseases (in particular, hypertension and diabetes) in terms of reducing the co-morbidity and mortality, thanks to the early intervention of those diseases. In other words, we would anticipate that an early intervention of COPD may be a new strategy for further improving the outcomes of COPD among the COPD patients with very few or no respiratory symptoms, who represent the majority proportion of the whole COPD population. 

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.



Tiotropium in Early-Stage Chronic Obstructive Pulmonary Disease

Yumin Zhou, M.D., Ph.D., Nan-shan Zhong, Ph.D., Xiaochen Li, M.D., Shuyun Chen, M.D., Jinping Zheng, M.D., Dongxing Zhao, M.D., Weimin Yao, M.D., Rongchang Zhi, M.D., Liping Wei, M.D., Bingwen He, M.D., Xiangyan Zhang, M.D., Changli Yang, M.D., Ying Li, M.D., Fenglei Li, M.D., Juan Du, M.D., Jianping Gui, M.D., Bin Hu, M.D., Chunxue Bai, M.D., Ping Huang, M.D., Gang Chen, M.D., Yongjian Xu, M.D., Changzheng Wang, M.D., Biao Liang, M.D., Yinhuan Li, M.D., Guoping Hu, M.D., Hui Tan, M.D., Xianwei Ye, M.D., Xitao Ma, M.D., Yan Chen, M.D., Xiwei Hu, M.D., Jia Tian, M.D., Xiaodan Zhu, M.D., Zhe Shi, M.D., Xiufang Du, M.D., Minjing Li, M.D., Shengming Liu, M.D., Ronghuan Yu, M.D., Jianping Zhao, M.D., Qianli Ma, M.D., Canmao Xie, M.D., Xiongbin Li, M.D., Tao Chen, M.D., Yingxiang Lin, M.D., Lizhen Zeng, M.D., Changxiu Ye, M.D., Weishu Ye, M.D., Xiangwen Luo, M.D., Lingshan Zeng, M.D., Shuqing Yu, M.D., Wei-jie Guan, Ph.D., and Pixin Ran, Ph.D.

N Engl J Med 2017; 377:923-935
September 7, 2017DOI: 10.1056/NEJMoa1700228

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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Last Updated on September 10, 2017 by Marie Benz MD FAAD