Study Clarifies Prevalence of Atypical Pathogen Infection in AECOPD

A recent study examined the prevalence and characteristics of 3 atypical pathogens responsible for respiratory tract infections in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD), as well as evaluated optimal detection methods.

Atypical pathogens that are associated with respiratory infections play an important role in the development of acute exacerbations of chronic obstructive pulmonary disease (AECOPD), potentially giving providers better insight into AECOPD etiology and best practices for selecting treatments, according to a recent study.

The study, published in the International Journal of Chronic Obstructive Pulmonary Disease, helps to clarify the discrepancy from previous research regarding the prevalence of atypical pathogens in patients with AECOPD. The investigators also evaluated clinical characteristics of different atypical pathogen infections and compared the accuracy of different detection methods.

“Overall, based on the results of this study, the sensitivity of serological testing is superior to that of sputum nucleic acid testing for atypical pathogens,” wrote the investigators.

The most common cause of AECOPD is respiratory tract infections associated with atypical pathogens, such as Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila.

Infections caused by atypical pathogens are usually diagnosed using indirect serological antibody testing and nucleic acid testing of sputum secretions without pathogen culturing. The specificity of nucleic acid tests using polymerase chain reaction (PCR) technology on secretions is high. However, study results have demonstrated that the sensitivity often varies, which the investigators said may be due to the collection method and site of the specimens to PCR testing.

Between March 2016 and November 2018, the investigators collected data from hospitalized patients with AECOPD from 11 medical institutions in 8 cities in China. Out of 366 patients with AECOPD who were admitted, 145 were included in the analysis after exclusion. The included patients had a mean (SD) age of 74.35 (10.07). Also, 70.34% were men, 66.21% were current smokers, and 63.45% had comorbidities.

After admission, sputum specimens were collected prior to antibiotic administration and again after about 2 weeks. The investigators used multiple detection methods, including a PCR method and analysis of urine samples, to detect fragments of Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila.

The overall positivity rate for Mycoplasma pneumoniaeI was 20.69% (n = 30/145). The highest positive rate was 20.00% when using a passive agglutination detection method compared with methods utilizing an enzyme immunoassay of immunoglobulin M (IgM) (2.75%; n = 4/145) or PCR (1.75%; n = 2/114).

The maximum body temperature, percentage of eosinophil, level of C-reactive protein, and level of procalcitonin were higher among patients who tested positive for Mycoplasma pneumoniaeI than patients who tested negative.

“This suggests that patients with AECOPD concomitantly infected with Mycoplasma pneumoniae have more severe airway hyperresponsiveness and systemic inflammation; the specific mechanisms underlying this phenomenon need to be clarified in further studies,” said the investigators.

Additionally, the overall rate of positivity for Chlamydia pneumoniae was 29.66% (n = 43/145). Use of a microimmunofluorescence assay was the only detection method to generate a positivity score for Chlamydia pneumoniae.

The overall positivity rate was 10.34% (n = 15/145) for Legionella pneumophila, with type 6 being the most common serotype observed. Among the 4 detection methods used, only 2 generated a positivity rate, including indirect fluorescent (10.34%; n = 15/145) and kits for IgM antibodies (0.69%; n = 1/145).

Although type 1 is more pathogenic than other serotypes, none of the 15 patients with Legionella pneumophila had the typical symptoms associated with the pathogen, such as high fever, cough with orange sputum, muscle aches, abdominal pain, or diarrhea.

“This finding suggests that for patients with AECOPD, the use of a urinary antigen kit that detects Legionella type 1 alone may not be sufficient to clarify whether a concomitant pulmonary infection caused by Legionella pneumophila is present,” wrote the investigators.

One limitation was the small number of patients, which the investigators said was likely because patients with COPD combined with pneumonia were excluded to ensure that all the patients had AECOPD.


Feng C, Xu M, Kang J, et al. Atypical pathogen distribution in Chinese hospitalized AECOPD patients: A multicenter cross-sectional study. Int J Chron Obstruct Pulmon Dis. Published online June 9, 2021. doi: 10.2147/COPD.S300779