Professor Liu Shengming

M.D., Professor, Chief Physician, Doctoral Supervisor and Postdoctoral Collaborator.

Director of Department of Internal Medicine, Department of Respiratory Medicine and Department of Internal Medicine Teaching and Research, The First Hospital of Jinan University.

Studied at Humboldt University, Germany from 1998 to 1999.

Academic undertakings:

• Member of the COPD Working Committee of the Respiratory Physician Branch, Chinese Medical Doctor Association
• Member of the COPD Alliance of the Respiratory Branch, Chinese Medical Association
• Vice Chairman of Respiratory Disease Branch of Guangdong Medical Association and Leader of Pulmonary Vascular Disease Group
• Vice Chairman of COPD Alliance of Respiratory Disease Branch, Guangdong Medical Association
• Vice Chairman of Respiratory Physician Branch of Guangdong Medical Doctor Association and Leader of Interstitial Disease and Lung Cancer Professional Group
• Vice Chairman of the Physician Branch, Guangdong Medical Doctor Association
• Member of the Standing Committee of Tuberculosis Branch, Guangdong Medical Association
• Vice Chairman of Respiratory Medicine Expert Committee, Guangdong Pharmaceutical Association
• Vice Chairman of Respiratory Professional Committee, Guangdong Health Management Society
• Member of the Cancer Prevention and Management Branch, Guangdong Provincial Hospital Association
• Deputy Director of Respiratory Physician Branch, Guangzhou Medical Doctor Association

At present, there is a lack of large-scale definitive epidemiological investigation data on bronchiectasis; however, in recent years, the incidence and prevalence of bronchiectasis reported internationally has increased, and this disease is becoming increasingly complex. To better understand the etiological distribution, diagnosis, treatment, and prevention of bronchiectasis, we invited Professor Liu Shengming from the first affiliated hospital of Jinan University to talk about the standardisation of antimicrobial therapy for bronchiectasis.

1. Epidemiology of bronchiectasis and stratified management of patients with different levels of disease severity

In 2013, Professor Zhou Yumin took the lead in conducting a survey of urban residents aged 40 years and above in seven cities. The survey showed that among the 10,811 respondents, 135 patients were previously diagnosed with bronchiectasis, corresponding to a prevalence of 1.5% in men and 1.1% in women.¹ However, the data in this study is not representative, and the prevalence rate might have been underestimated owing to the lack of chest CT examination, which requires a large-scale epidemiological investigation and study.

The “Chinese Expert Consensus on the Diagnosis and Treatment of Adult Bronchiectasis”, published in 2021, proposed the need to assess the severity of the disease for stratified management of patients. In clinical practice, the severity of bronchiectasis is often assessed through imaging evaluation, for which the modified Reiff score is commonly used. However, due to the significant heterogeneity of the onset of bronchiectasis, there is no close correlation between imaging evaluation and the severity of bronchiectasis. Scholars in China and other countries instead recommend a multi-dimensional perspective, combining the patient’s clinical symptoms, imaging findings, risk of acute exacerbation, and bacterial colonisation, the Bronchiectasis Severity Index (BSI) and E-FACED score, which have been designed and confirmed to be useful to assess the severity of bronchiectasis.²

2. Differences in pathogenic distribution and selection of antimicrobial treatment options between the stable phase and acute exacerbation of bronchiectasis

From limited epidemiological data in China, there appears to be no significant difference in etiological distribution between the stable phase and acute exacerbation of bronchiectasis, both of which are dominated by Gram-negative bacilli,³ but there are certain differences in the detection rate of bacteria. Studies have shown that the detection rate of bacteria in patients with stable bronchiectasis is mostly below 30%, and the positive rate of sputum culture in acute exacerbation stage is slightly higher, ranging from 30–50%. Pathogens of bronchiectasis are mainly Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, Moraxella catarrhalis, Enterobacter cloacae, Acinetobacter baumannii, Haemophilus parainfluenzae, etc. The detection rate of Pseudomonas aeruginosa ranked first in both the stable phase and the acute exacerbation of bronchiectasis.

Regarding antimicrobial therapy in the stable phase, the pathogens detected need to be assessed, and most of the pathogens detected in the stable phase are likely to be colonising bacteria. The need for their removal mostly depends on the pathogenic species. If Pseudomonas aeruginosa is isolated from a patient who is diagnosed with bronchiectasis for the first time, with imaging studies and symptoms are suggestive of progressive disease, then pathogen eradication therapy is recommended.² The recommended regimen is ciprofloxacin 500 mg bid orally for 2 weeks, followed by inhalation of antimicrobial drugs such as tobramycin or polymyxin for 3 months. However, these inhalation dosage forms are not yet available in China, and clinical use of intravenous injection instead of nebulization does not strictly implement pathogen clearance. The application dose of ciprofloxacin is also different from that in other countries (500-750 mg bid). ² In patients from whom Pseudomonas aeruginosa has not been isolated, or whose condition is stable, pathogen clearance therapy is not clinically advocated. In addition, if other pathogenic bacteria (non-Pseudomonas aeruginosa) are isolated, pathogen clearance therapy is not recommended. Overall, there is a need for evidence-based medical evidence to support pathogen clearance therapy for bronchiectasis patients in China.

The treatment of acute exacerbation of bronchiectasis requires comprehensive management, and antimicrobial therapy is the key.² Sputum culture and drug sensitivity test should be submitted before initiating empirical antimicrobial therapy; patients with no previous sputum culture results should be routinely covered for Pseudomonas aeruginosa and drugs with anti-Pseudomonas aeruginosa activity should be selected. Over the past few years, newly marketed drugs with anti-Pseudomonas activity, such as ceftazidime/avibactam and the new quinolone sitafloxacin, can be used as treatment options.²

When clinical efficacy is inadequate, antimicrobial drugs should be adjusted according to the results of the drug sensitivity test, and sputum should be resubmitted for culture. If possible, bronchoalveolar lavage and brush samplling can be used for microbial culture.²

3. The clinical benefit of long-term low-dose macrolide use during stable bronchiectasis

Long-term low-dose oral administration of macrolides can be the treatment of choice for preventing recurrent acute exacerbations in patients with bronchiectasis; not primarily for their antimicrobial effects, but for their immunomodulatory effects.² However, the evidence-based data supporting this recommendation primarily comes from studies in Western patient populations, and study sample sizes are small. Long-term oral administration of low-dose macrolides has been shown to be beneficial in reducing sputum volume and the number of acute exacerbations in patients, but it may increase the risk of gastrointestinal adverse reactions and bacterial drug resistance.

There may be clinical benefit for specific patient populations: (i) those with ≥3 acute exacerbations per year; (ii) those with high-risk factors for acute exacerbations such as immunodeficiency; and (iii) those with <3 acute exacerbations per year despite optimal primary and etiologic treatment, or when acute exacerbations have a greater impact on the patient’s health.²

In China, there are fewer clinical studies on long-term low-dose oral administration of macrolides; such treatment is usually administered no more than 3 months, unless the patient has NTM (nontuberculous mycobacterial lung disease). Antibiotic abuse and resistance in China have always been problems that clinicians need to be vigilant about; thus, the suitability of long-term low-dose oral macrolides for China’s population needs to be further explored.

4. According to an article published in 2021 titled ‘Chinese Expert Consensus on the Diagnosis and Treatment of Adult Bronchiectasis’, pathogen clearance treatment is recommended for bronchiectasis patients who are first isolated Pseudomonas aeruginosa and whose disease has progressed. What is your opinion about this statement? And how do you see the clinical value and prospect of the new quinolone sitafloxacin tablets in the antibacterial treatment of bronchiectasis?

The first-generation quinolones are rarely used in clinical practice at present due to their efficacy and adverse reactions. Ciprofloxacin is not a respiratory quinolone, but it plays a crucial role in urinary tract infections and is currently the drug of choice for the treatment of Pseudomonas aeruginosa infections.⁵ The respiratory quinolone levofloxacin has the advantages of broad spectrum, high sensitivity, and strong activity against Pseudomonas aeruginosa, and is one of the most widely used quinolone antibacterial drugs in clinical practice.⁶

Pseudomonas aeruginosa is the predominant causative agent in both the stable phase and acute exacerbations of bronchiectasis.^7,8 Pseudomonas aeruginosa clearance therapy can reduce the frequency of acute exacerbations and shorten the length of hospitalisation and hospitalisation rates.⁹ The new quinolone sitafloxacin has high concentration in lung tissue and covers the common causative agents of bronchiectasis, such as Pseudomonas aeruginosa, Klebsiella, Escherichia coli and Haemophilus influenzae, with strong antibacterial activity. Also, the safety of sitafloxacin is comparable to that of levofloxacin,¹⁰ which provides a good therapeutic option for the antimicrobial treatment of bronchiectasis.

In addition, for pathogen clearance in the stable phase of bronchiectasis, oral preparations are the most used preparations in China. The development of inhalation preparations with a good safety profile will be more conducive to long-term benefits for patients, which is also a common expectation in clinical practice.

References:

1. Zhou Y, et al. Chinese Journal of Internal Medicine [translated title] 2013;52(5):379‐
2. Bronchiectasis Expert Consensus Writing Collaborative Group, Infectious Disease Group, Chinese Society of Respiratory Diseases. Chinese Journal of Tuberculosis and Respiratory Medicine [translated title] 2021;44(04):311-321.
3. Zhou Jia, et al. Chinese Journal of Hospital Infection 2019;29(24):3764-3768.
4. Lee SH, et al. J Clin Med 2018;7(11):429.
5. Instruction on Ciprofloxacin
6. Instruction on Levofloxacin
7. Hill AT, et al. Thorax 2019;74(Suppl 1):1‐
8. Polverino E, et al. Eur Respir J 2017;50(3).
9. White L, et al. Respir Med 2012;106(3):356‐
10. Instruction on Sitafloxacin