Professor Zhao Ziwen
Second Affiliated Hospital of South China University of Technology, Guangzhou First Municipal People’s Hospital
Director and Deputy Director, Department of Respiratory and Critical Care
Doctoral advisor, Master’s advisor
Deputy Chairman of the Professional Committee, China Medicine Education Association Respiratory Disease Rehabilitation
Standing Committee Member, Non-Tuberculous Mycobacterium Professional Branch of the Anti-Tuberculosis Association of China
Member, COPD Group of the Chinese Thoracic Society
Member, Critical Care Group of the Chinese Thoracic Society
6^th and 7^th Vice Chairman, Respiratory Disease Branch of Guangdong Medical Association
Vice Chairman, Tuberculosis Branch of Guangdong Medical Association
Vice Chairman, Respiratory Physician Branch of Guangdong Medical Doctor Association
Leader, COPD Group of the Respiratory Disease Branch of Guangdong Medical Association
Chairman, Guangdong COPD Alliance
Vice Chairman, Respiratory Professional Committee of Guangdong Health Management Association
Vice Chairman, Respiratory Professional Committee of Guangdong Preventive Medicine Association
Chairman, Respiratory Physician Branch of Guangzhou Physician Association
Editorial Committee of Thorax (Chinese edition); Editorial Board of Chinese Medical Journal, Chinese Journal of Tuberculosis and Respiratory Diseases, and Chinese Journal of Tissue Engineering
Winner of the National and Guangdong Provincial May Day Labour Award, and Guangzhou Model Worker Award
Awarded Guangdong Province Anti-SARS Outstanding Individual Top Award
Received the Guangdong Science and Technology Progress Award Special Prize, Respiratory Disease Branch of Chinese Medical Association Influential Academic Paper Award

Introduction: In the field of anti-infective treatment of acute exacerbation of COPD, the broad spectrum and potent antimicrobial agent sitafloxacin stands out as the preferred choice.

Chronic obstructive pulmonary disease (COPD) is a common and severe disease that significantly impacts the quality of life of affected individuals. It stands as one of the major causes of mortality, imposing substantial economic burden to patients, their families and society. According to the results of the “Chinese Adult Pulmonary Health Study” survey led by Professor Wang Chen in 2018, the prevalence of COPD among Chinese adults aged 20 and above was 8.6%, reaching a staggering 13.7% among adults aged 40 and above. The estimated number of COPD patients in the nation is close to 100 million¹, indicating a persistently high incidence of COPD in China. According to the Global Burden of Disease Survey, COPD ranked as the fifth leading cause of mortality in China in 2016².

As such, it is of great clinical significance to standardise the diagnosis and treatment of patients with COPD, as well as to improve the prognosis of patients by preventing the occurrence of acute exacerbations. In this aspect, the “Medical Community” platform is honoured to have Professor Ziwen Zhao from Guangzhou First Municipal People’s Hospital to share insights regarding the diagnosis and treatment-related issues of COPD.

Challenges in the diagnosis and treatment of COPD: Emphasising prevention of acute exacerbations

“For large grade A tertiary hospitals, the diagnosis of COPD may not be challenging, but non-specialist physicians often overlook or misdiagnose COPD. Primary medical institutions are less inclined to conduct pulmonary function examinations on patients with recurrent cough. This is partly due to the lack of profound understanding of COPD among primary care physicians. Another reason is the inadequate facilities for pulmonary function tests, resulting in many patients being unable to undergo the comprehensive examination. These are the practical issues faced in the clinical diagnosis of COPD,” Professor Zhao Ziwen stated.

In China, due to the aforementioned issues, many local patients with COPD are being overlooked, resulting in many patients being diagnosed with COPD only after being hospitalised for acute exacerbations, at which point they are already at the advanced stage of the disease. Professor Zhao Ziwen conveyed that he believes that early diagnosis and early intervention for patients with COPD are crucial for improving patients’ prognoses.

Concerning the diagnosis and treatment of acute exacerbation of COPD (AECOPD), Professor Zhao Ziwen pointed out that, according to the latest GOLD 2023 guidelines, the assessment of the severity of COPD has been simplified by combining the high-risk C and D groups into the acute exacerbation group E. However, for the majority of patients with acute exacerbations, there are no specific measures in routine treatment, and the deterioration of pulmonary function is challenging to reverse. Hence, the clinical focus remains on the prevention of acute exacerbations, which is one of the important goals in the current clinical management of COPD.

Infection-induced acute exacerbation of COPD: Quinolones as a key treatment

The occurrence of events is driven by underlying causes. Infection stands out as one of the primary triggers of AECOPD. Professor Zhao Ziwen pointed out that COPD patients are susceptible to increased airway mucus secretion and aggravated airflow obstruction due to respiratory infections. This manifests as worsening dyspnoea, increased sputum volume, and purulent sputum, often accompanied by intensified coughing and wheezing. Professor Zhao Ziwen emphasised that anti-infective treatment is crucial for patients with bacterial infections, especially for those with recurrent acute exacerbations.

In clinical practice, when administering antimicrobial treatment for infection-induced AECOPD, the management typically adheres to protocols for community-acquired infectious diseases. The microorganisms isolated from the sputum of patients with AECOPD are commonly pathogens associated with community-acquired infectious diseases. According to statistics, 40%–60% of patients with AECOPD have bacteria isolated from their sputum, with the most common pathogens being Haemophilus influenzae, Moraxella catarrhalis, Mycoplasma pneumoniae and Streptococcus pneumoniae, followed by Pseudomonas aeruginosa, gram-negative Enterobacteriaceae, Staphylococcus aureus and Haemophilus parainfluenzae³.

In terms of medication selection, Professor Zhao Ziwen shared that, from his personal clinical experience, most clinicians will choose quinolones as antibacterial treatment for AECOPD. Most patients show significant improvements in infections, sputum volume, cough and haemoptysis after treatment. In analysing the underlying reasons, the efficacy is attributed not only to the sensitivity of common pathogenic bacteria of AECOPD to quinolones; rather, these drugs also offer broad coverage against atypical pathogens. Furthermore, the once-daily administration can effectively improve patients’ infection. Notably, the new quinolone sitafloxacin offers broad-spectrum coverage against common gram-positive bacteria, gram-negative bacteria, anaerobic bacteria, and atypical pathogens. Drug-resistant bacteria, such as Pseudomonas aeruginosa and Staphylococcus aureus, are also highly sensitive to the drug. This provides clinicians with another new antibacterial arsenal that can be used as a preferred medication for the anti-infectious treatment of AECOPD.

Eradication of Pseudomonas aeruginosa or Mycoplasma through quinolone antibacterial drugs

Among many bacteria, Professor Zhao Ziwen specifically highlighted Pseudomonas aeruginosa, which has gained prominence in recent years. Studies indicated that Pseudomonas aeruginosa constitutes approximately 13.0%–35.0% of the pathogenic bacteria isolated from patients with AECOPD, with a higher isolation rate correlated with poorer pulmonary function⁴. Professor Zhao Ziwen pointed out that conventional treatment for Pseudomonas aeruginosa infections often involved cephalosporins, macrolides and other drugs, yet drug resistance remains a prevalent challenge.

The widespread issue of drug-resistant Pseudomonas aeruginosa has impeded the effectiveness of many antimicrobial treatments for AECOPD. However, with the advent of new antimicrobial drugs, there seems to be a breakthrough in overcoming this resistance issue. “Currently, drugs with anti-Pseudomonas aeruginosa activity in clinical practice include β-lactams, fluoroquinolones, aminoglycosides, and polymyxins. Among them, concentration-dependent fluoroquinolone antibacterial drugs, such as sitafloxacin and levofloxacin, exhibit the highest correlation between AUC/MIC and clinical effectiveness. Their clinical efficacy is significantly superior to using cephalosporins alone, especially in outpatient settings,” according to the analyses by Professor Zhao Ziwen.

Besides Pseudomonas aeruginosa, mycoplasma infection is also one of the important factors leading to the occurrence of AECOPD. Professor Zhao Ziwen discussed about Mycoplasma pneumoniae, which has been trending recently, and offered his personal perspective. He conveyed that the actual situation of Mycoplasma pneumoniae infection in children is far less severe than what is being reported online, attributing this discrepancy to the non-standardised diagnosis of Mycoplasma pneumoniae infection.

Professor Zhao Ziwen then stated that although there are limited drug options for Mycoplasma pneumoniae infection in children, there are many drug options to treat the same condition for adults. In addition to macrolide antibiotics such as azithromycin, tetracyclines and quinolones are also viable options. “In particular, the clinical treatment course of sitafloxacin typically spans one week, yielding satisfactory results in the management of adult Mycoplasma infections,” added Professor Zhao Ziwen.

Conclusion

In the concluding remarks of the interview, Professor Zhao Ziwen expressed optimism for the future development in the field of clinical AECOPD. He expressed his belief that, as the academic community further explores the subject of AECOPD, the challenges in clinical diagnosis and treatment will be systematically addressed. In terms of anti-infective treatment, he also looks forward to widespread application of novel quinolones such as sitafloxacin, which will benefit more patients.

References:

1. Wang C, Xu J, Yang L, et al. Prevalence and risk factors of chronic obstructive pulmonary disease in China (the China Pulmonary Health [CPH] study): a national cross-sectional study. Lancet. 2018;391(10131):1706-1717.
2. GBD 2016 Causes of Death Collaborators. Global, regional, and national age-sex specific mortality for 264 causes of death, 1980-2016: a systematic analysis for the Global Burden of Disease Study 2016 [published correction appears in Lancet.2017 Oct 28;390(10106):e38].Lancet. 2017;390(10100):1151-1210.
3. [Chinese Expert Consensus on the Diagnosis and Treatment of Acute Exacerbation of Chronic Obstructive Pulmonary Disease (2023 revised edition)] [J] . International Journal of Respiration, 2023, 43(2) : 132-149.
4. [Chinese expert consensus on the management of lower respiratory tract infections of Pseudomonas aeruginosa] [J]. Chinese Journal of Tuberculosis and Respiratory Diseases, 2022,45(8) : 739-752