Asthma is a heterogeneous disease manifesting with airway inflammation (1). This disease is defined by the presence of respiratory symptoms that vary over time and in intensity, together with variable expiratory airflow limitation (2). Inadequate control of asthma may lead to frequent exacerbations, worse health status, and poor quality of life (3). Asthma is also found to be associated with respiratory system infections, but information on the underlying mechanism of this predisposition is limited (4). Altered epithelial microenvironment and impaired immune function may contribute to the susceptibility of respiratory system infections (5, 6).

Pleural empyema indicates the occurrence of frank pus within the pleural space (7). It is most commonly caused by respiratory system infections, such as pneumonia (8). Mortality rate among individuals having pneumonia with pleural empyema is far higher than in patients who do not have pleural empyema (9, 10). The crucial nature of pleural empyema and the need for removal have been identified for several centuries (11). Delayed diagnosis and poor drainage have been found to be linked with high mortality (12). Alcohol consumption, substance use, diabetes mellitus, immunosuppression, malignancy, pulmonary disease, and prior occurrence of pleural effusion are predictors of the development of pleural empyema (13, 14).

Several studies have investigated the association between asthma and respiratory system infections (15–18). However, the studies did not examine the incidence of pleural empyema in asthma patients. Pleural empyema is a noticeable infection of the respiratory system and requires timely treatments, such as antibiotic therapy, pleural drainage, intrapleural fibrinolysis, and surgery. Thus, investigating the risk of pleural empyema in patients with asthma is necessary. This study aimed to examine whether patients with asthma have a higher risk of pleural empyema development. In addition, we attempted to assess the effect of asthma control on the occurrence of pleural empyema.

We recruited an asthma group comprising 48,360 patients and a comparator group of 48,360 individuals (Table 1). Age and gender did not significantly differ between asthma and comparator group. The mean age ± standard division of asthma and comparator group was 54.9 ± 18.7 and 54.1 ± 18.5 years, respectively. Approximately 52% of the individuals were women in both groups. The major comorbidities of the asthma group were COPD (24.8%), CLD (21.7%), followed by diabetes mellitus (10.9%), stroke (6.93%), and cancer (3.16%). The mean follow-up periods were 7.72 ± 4.15 years in the asthma group and 8.03 ± 4.02 years in the comparator group. The proportion of corticosteroid use were 23.6% in the asthma group and 15.2% in the comparator group. Figure 1 showed that patients with asthma had a higher cumulative incidence of pleural empyema than individuals without asthma throughout the 14-year study period.

The overall incidence density rates of pleural empyema were 8.65 and 4.25 per 10,000 person-years in asthma and comparator groups, respectively (Table 2). Compared with the comparator group, the corresponding adjusted HR (aHR) of pleural empyema was 2.12 (95% CI = 1.76–2.56) in the asthma group after adjusting for age, gender, COPD, diabetes mellitus, CKD, CLD, stroke, cancer, and corticosteroid use. Compared with persons aged 20–49, the aHRs of pleural empyema were 2.43-fold higher in those aged 50–64 (95% CI = 1.80–3.29) and 4.10-fold higher in those aged ≥65 (95% CI = 3.09–5.44). The aHR of pleural empyema was 2.55-fold higher for men relative to women (95% CI = 2.09–3.12). Moreover, the risk of pleural empyema was higher in persons with stroke (aHR = 2.68, 95% CI = 2.12–3.38), diabetes mellitus (aHR = 1.86, 95% CI = 1.50–2.31), and COPD (aHR = 1.48, 95% CI = 1.22–1.79) compared with subjects without these comorbidities.

Further analyses revealed that the incidences and aHRs of pleural empyema for the asthma group were all significantly higher compared with the comparator group after stratification for age, gender, presence of comorbidities, and corticosteroid use (Table 3). In addition, we assessed the impact of the frequency of asthma-related emergency room visits and hospital admissions on the development of pleural empyema among the asthma group (Table 4). A higher frequency of annual asthma-related emergency room visits and hospital admissions raised the risk of pleural empyema development (both p for trend <0.001). Moreover, we analyzed cumulative corticosteroid doses on pleural empyema development among the asthma group (Table 4). The incidence of pleural empyema was higher in those with corticosteroid use; however, the p value for trend was not significant (p = 0.25).

We believed that this investigation is the first population-based retrospective cohort study to evaluate the incidence of pleural empyema in patients with asthma. Our findings revealed that patients with asthma have a significantly higher risk of developing pleural empyema than those without asthma. The risk of pleural empyema was also larger in older people, in males, those with comorbidities. Furthermore, the hazards of pleural empyema were significantly larger in the asthma cohort compared with the comparison cohort under stratification by age, gender, comorbidity, and corticosteroid use. Moreover, we found that the risk of pleural empyema was higher in asthma patients with an increased number of asthma-related emergency medical demands and hospital admissions, indicating that the level of asthma control may influence the occurrence of pleural empyema.

The mechanism between asthma and pleural empyema remains largely unknown. Patients with asthma who are susceptible to pneumonia may still play a major role. This condition may be driven by the following: (1) a large prevalence of carriage of the bacteria, (2) a disordered immune response from exposure to the bacteria, (3) impaired bacterial clearance, and (4) a suboptimal response to vaccination (5). Parapneumonic pleural effusions are known to represent a common complication of pneumonia and can be found in approximately 40% of bacterial pneumonia cases (11). In addition, inhaled or systemic corticosteroid use, shared comorbidities, cigarette smoking, alcohol consumption, unhealthy lifestyle, poor self-care, and poor physical health are commonly noted among asthma patients. These factors are also related to the development of pneumonia and pleural empyema (9).

Inconsistent evidence was found between chronic inflammatory airway disease and the development of pleural empyema. Lu et al. (19) conducted a case-control study to evaluate the potential risk factors of pleural empyema. They enrolled 1,851 pleural empyema cases and 7,404 non-empyema controls and found significant factors that lead to pleural empyema include the following: aspiration history [odds ratio (OR) = 7.28, 95% CI = 5.00–10.6)], human immunodeficiency virus infection (OR = 5.66, 95% CI = 1.38–23.2), malnutrition (OR = 2.86, 95% CI = 2.07–3.95), cancer (OR = 2.74, 95% CI = 2.28–3.30), diabetes mellitus (OR = 2.25, 95% CI = 1.96–2.59), stroke (OR = 1.99, 95% CI = 1.70–2.34), CKD (OR = 1.78, 95% CI = 1.42–2.25), chronic obstructive pulmonary disease (COPD, OR = 1.72, 95% CI = 1.47–2.01), asthma (OR = 1.34, 95% CI = 1.15–1.57), and CLD (OR = 1.20, 95% CI = 1.06–1.35). In another study, Lu et al. evaluated COPD and the subsequent development of pleural empyema (20). They enrolled 55,136 COPD cases and 98,769 non-COPD controls and found that the incidence of pleural empyema was 3.64-fold higher in the COPD cohort than in the comparison cohort (15.8 vs. 4.34 per 10,000 person-years), with a corresponding aHR of 3.25 (95% CI = 2.73–3.87). These findings may suggest that chronic inflammatory airway disease may contribute to the development of pleural empyema. By contrast, Dusemund et al. (21) performed a case-control study in Switzerland to investigate outcomes of community-acquired pneumonia in patients with chronic lung disease. They found that the incidence of pleural empyema was insignificant in asthma [0.5% (asthma) vs. 0.9% (controls), p = 0.141] and COPD [0.5% (COPD) vs. 0.5% (controls), p = 0.817]. In addition, Elemraid et al. (22) assessed predictors of pleural empyema development in children. They found that age, sex, mother's age, smoking among the child's parents, poverty, nursery attendance, asthma, and household characteristics (bedrooms and number of occupants) were not significantly related. Therefore, we may need additional investigations to clarify this issue.

An increased risk of pleural empyema occurrence was observed in adult patients with asthma compared to those without asthma. Furthermore, the risk of pleural empyema may increase with the degree of asthma control.

The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.

W-CL, T-CS, C-YT, T-CH, and W-HH: conception and design. C-YT, T-CH, and W-HH: administrative support. W-CL, C-LL, and T-CS: collection and assembly of data and data analysis and interpretation. All authors: manuscript writing and final approval of manuscript.

This study was supported by China Medical University Hospital (DMR-110-033).

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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