Patients with AECOPD have bacterial or viral infections as the primary trigger, with non-infectious factors including air pollution, allergy, sedation, congestive heart failure, and pulmonary embolism, and a small percentage of patients without clear triggers. Infections of the lower whistle tract are the most common and bacteria are the main infectious agents.
A recent study showed that bacteria could be isolated from lower whistle secretions in 69% of patients with AECOPD, with Haemophilus influenzae being the most common, followed by Streptococcus pneumoniae and Catamorax, and Pseudomonas aeruginosa and other gram-negative bacteria being less common. However, the isolation rate of P. aeruginosa and gram-negative bacteria was significantly higher in patients with severe AECOPD requiring mechanical ventilation.
In addition, bronchoscopy suggested that bacterial colonization of the lower whistle tract was present in 25% of patients with stable COPD and up to 50% of patients with AECOPD. Further examination of bronchial mucosa specimens revealed that the bacterial infection sites were mostly in the tracheal lumen, airway mucosal surface and mucosal tissues, mainly causing an airway inflammatory response. Moreover, the greater the bacterial load in the airway, the heavier the inflammatory response caused in the airway. Therefore, the total bacterial load in the airways is significantly and positively correlated with the degree of airway inflammation and lung function decline.
In recent years, the bacterial “threshold hypothesis” (see Figure 2: the curve represents the concentration of potentially pathogenic microorganisms in the lower whistle tract) has been proposed to explain the role of bacterial infection in AECOPD. This hypothesis suggests that increased airway bacterial load causes increased airway inflammation, leading to AECOPD, and that bacterial colonization of the lower whistle tract is known to exist in COPD patients, meaning that low concentrations of potentially pathogenic microorganisms are present in the whistle tract.
In some specific cases, potentially pathogenic microorganisms can proliferate (shown in the graph as the rising phase of the curve) and cause an inflammatory response. After antibiotic treatment (AB1, AB2, AB3), the clinical symptoms disappear if the concentration of potentially pathogenic microorganisms drops below the clinical threshold.
Antibiotics can reduce the concentration of bacteria, but if they cannot be completely removed, after a period of time, their concentration will rise again and acute exacerbation will occur again. The stronger the antibiotic effect, the faster the concentration of potentially pathogenic microorganisms decreases and the longer the time until the next acute exacerbation.
The severity of COPD is related to the type and distribution of the pathogen. In patients with severe COPD, especially those requiring mechanical ventilation, the isolation rate of Pseudomonas aeruginosa and Gram-negative bacteria is significantly higher.
Treatment: relying on initial experience with antimicrobial therapy
Comprehensive determination of antibiotic indications
Studies have shown that the bacterial load in the airway increases in AECOPD, and the inflammatory mediators (such as leukotrienes, interleukins and tumor necrosis factor) in the airway also increase significantly. After antibiotic treatment, the levels of airway inflammatory mediators and myeloperoxidase decreased significantly in those who cleared the bacteria, while maintaining the same levels in those who did not clear the bacteria, indicating that antibiotics cleared the bacteria and also suppressed airway inflammation, i.e., antibiotics are beneficial for AECOPD treatment.
The indications for antibiotic use should be based on a comprehensive judgment of the condition and clinical symptoms of patients with AECOPD. Both the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines and the European Society of Whistling (ERS) suggest that the following patients with AECOPD need to receive antibiotic therapy.
(1) Patients with AECOPD who have the 3 main symptoms of increased dyspnea, increased sputum, and purulent sputum;
(2) Patients with AECOPD with two of the three main symptoms mentioned above, one of which is sputum production;
(3) Patients with AECOPD who are critically ill and require non-invasive or invasive mechanical ventilation.
Minimizing bacterial load
Initial empiric therapy is important because of the low rate of positive sputum specimen cultures and the time required.The antibiotic use recommended by GOLD and ERS according to the appropriate pathogen stratification for COPD severity, the local prevalence of drug resistance, and the presence or absence of risk factors for P. aeruginosa infection is shown in Table 2.
It is important to note that the severity of AECOPD varies widely and clinical anti-infective therapy requires adequate assessment of risk factors affecting prognosis. Intensive antimicrobial therapy (mainly for gram-negative bacilli) should be indicated for any 2 of the following indicators: more than 3 acute exacerbations in a short period of time, multiple antibiotic therapy, failure of previous antibiotic therapy, history of mechanical ventilation, previous history of lower whistle tract gram-negative bacilli colonization or infection, long-term systemic hormone application, need for oxygen therapy, smoking and severe co-morbidities (immunosuppression, HIV infection, malignancy, etc). malignancy, etc.).
Antimicrobial therapy should reduce the bacterial load to the lowest possible level to prolong the interval of AECOPD. However, the long-term application of broad-spectrum antibiotics and glucocorticoids is prone to secondary deep fungal infections, so attention should be paid to the course of antibiotic administration.
Choice of antibiotic regimen
Currently, the duration of antibiotic administration in GOLD guidelines is recommended to be 3-7 days. This meta-analysis (which included 21 clinical studies with a total of 10,698 patients) examined the comparison of different antibiotic durations in patients with mild to moderate acute exacerbations of chronic bronchitis and AECOPD and found no significant differences in clinical cure and bacteriologic cure indices for short-term antibiotic applications ≤5 days compared with standard courses of 7-10 days, but the former had a significantly increased safety profile. Therefore, a short course of antibiotic therapy is recommended for patients with mild to moderate AECOPD, while the duration of antibiotic administration may be appropriately prolonged for critically ill patients using invasive mechanical ventilation or patients with multiple drug resistance to Gram-negative bacillary infections, with the premise of preventing secondary deep fungal infections.
Assessment and identification: biological indicators may be the guide
A survey in the United States involving 360 hospitals and including 69,820 patients hospitalized with AECOPD showed that 85% of patients were on antibiotics, but not all patients benefited from anti-infective therapy, and patients with severe disease or evidence of bacterial infection with AECOPD benefited more. Therefore, it is clinically important to guide antibiotic use in AECOPD with clear biological indicators.