Introduction

Pneumomediastinum, defined as the presence of free-air within the mediastinum, can be divided into two types: spontaneous or secondary. Secondary pneumomediastinum may commonly occur in situations which can damage the esophagus or airway such as trauma, surgery, and other interventions, or by gas-forming mediastinal infections. In contrast, primary spontaneous pneumomediastinum (PSPM) is a diagnosis of exclusion and is rare, but mainly benign disease [1].

Although occasionally obvious precipitating factors cannot be identified in patients with PSPM, previous studies reported that there were benign precipitating factors including asthma, smoking, coughing, vomiting, training, or etc. for PSPM [2]. However, despite previous studies on PSPM [3–6], the disease was relatively poorly understood because most previous research have been conducted in fewer than 100 patients with PSPM, and research including over 100 patients is scarce [7]. In addition, since recurrent spontaneous pneumomediastinum (RSPM) is far rare, not much published information was available on RSPM and furthermore, not many studies have evaluated whether there was associated factor with RSPM [8, 9].

Therefore, the aim of this study was 1) to evaluate the precipitating factors and symptoms of PSPM in a relatively large sample size at a single-center with over a 10-year period and 2) to assess the factors related with RSPM.

Materials and methods

Study population

This single-center retrospective study was approved by our institutional review board, which waived the requirement for informed consent.

From January 2010 to December 2021, 237 patients with their first diagnosed PSPM were eligible for inclusion in this study. All the study patients underwent unenhanced or contrast-enhanced chest computed tomography (CT) (Fig 1) and underwent chest radiographs on a daily basis until they were discharged. During the follow-up period, patients with recurrent spontaneous pneumomediastinum were classified into “recurrence” group and those without recurrent pneumomediastinum were classified into “no recurrence” group.

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Fig 1. Representative cases of primary spontaneous pneumomediastinum (PSPM) on chest computed tomography (CT).

(A) pneumomediastinum without other combined complication, (B) pneumomediastinum (arrowhead) with left pneumothorax, and (C) pneumomediastinum with subcutaneous emphysema (arrow) at anterior chest wall (left > right).

https://doi.org/10.1371/journal.pone.0289225.g001

Results

Clinical findings

Most of study population was men (93.7%) (men: women = 222: 15). Most frequent symptom was acute chest pain (n = 211, 89.0%), followed by acute neck pain (n = 123, 51.9%), and dyspnea (n = 78, 32.9%). The 1^st precipitating factor was cough (n = 72, 30.4%), followed by upper respiratory infection (n = 66, 27.8%), physical exertion (n = 56, 23.6%), and retching/vomiting (n = 34, 14.3%). There was no precipitating factor in 29 of 237 patients (12.2%). Of the 92 patients with smoking history (38.8%), 66 patients were ex-smokers and 26 patients were current smokers. In 99 patients with asthma history (41.8%), 88 patients had mild intermittent or mild persistent asthma, and 11 patients had moderate persistent asthma. There was no patient with severe persistent asthma. Subcutaneous emphysema and pneumothorax was combined in 6 patients (2.5%) and 9 patients (3.8%), respectively (Table 1). In cases of pneumothorax, the presence of pneumomediastinum did not change the standard treatment.

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Table 1. Baseline characteristics of the study patients.

https://doi.org/10.1371/journal.pone.0289225.t001

Factors associated with recurrent spontaneous pneumomediastinum

During the mean follow-up period of 48.6 ± 30.9 months, RSPM occurred in 11 patients (4.6%). The proportion of smokers (72.8% vs. 37.1%) and current smokers (36.4% vs. 9.7%) was significantly higher in “recurrence” group than “no recurrence” group (p = 0.010). Furthermore, not only the proportion of patients with asthma (81.8% vs. 39.8%), but that of patients with moderate persistent asthma (27.3% vs. 3.5%) was also significantly higher in “recurrence” group than “no recurrence” group (p < 0.001). There was no significant difference in age, sex, presenting symptoms, precipitating events, and combined thoracic disease between two groups (Table 1). One patient with pneumothorax in the recurrence group had no pneumothorax during the first episode.

Table 2 showed associations of selected factors with RSPM. On univariate analysis, current smoker (OR = 5.051, 95% CI = 0.922–35.455, p = 0.060) and asthma (mild intermittent/mild persistent asthma, OR = 4.082, 95% CI = 1.001–9.130, p = 0.038; moderate persistent asthma, OR = 6.061. 95% CI = 1.017–35.714, p = 0.001) were the related factors to recurrence. However, multivariate analysis showed that asthma was the only factor associated with a higher risk of RSPM (mild intermittent/mild persistent asthma, OR = 7.092, 95% CI = 0.925–29.619, p = 0.047; moderate persistent asthma, OR = 8.000, 95% CI = 1.000–40.000, p = 0.011).

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Table 2. Univariate and multivariate analysis for predictors of recurrent pneumomediastinum.

https://doi.org/10.1371/journal.pone.0289225.t002

Discussion

In the present study, all the 237 patients with PSPM showed benign clinical course without morbidity nor mortality. Most frequent symptom was acute chest pain (89.0%), followed by acute neck pain (51.9%), and dyspnea (32.9%). The 1^st precipitating factor was cough (30.4%), followed by upper respiratory infection (27.8%), physical exertion (23.6%), and retching/vomiting (14.3%). During the mean follow-up period of 48.6 ± 30.9 months, RSPM occurred in 11 patients (4.6%). On multivariate regression analysis, asthma was the only associated factor with RSPM (mild intermittent/mild persistent asthma, OR = 7.092, 95% CI = 0.925–29.619, p = 0.047; moderate persistent asthma, OR = 8.000, 95% CI = 1.000–40.000, p = 0.011).

Though there have been previous studies regarding PSPM, the present study with relatively large sample size was conducted to improve the understanding of PSPM and RSPM, since research on over 100 patients with pneumomediastinum is scarce. The results of our single-center study are in many ways consistent with previous reports. First, our result shows that PSPM is a self-limited and benign disease; thus, specific treatment may not be required in PSPM patients without concurrent pneumothorax. Second, the mean age was 23.4 ± 3.4 years (median: 22 years, IQR: 21–25 years) and the proportion of men was overwhelmingly high (222/237, 93.7%), concordant with the existing knowledge that PSPM generally affected young adult males [11, 12]. Third, chest pain was the most common symptom and common precipitating events included cough, physical exertion, and retching/vomiting. Furthermore, smoking and asthma were common histories in patients with PSPM [7].

In this study, the recurrence rate of spontaneous pneumomediastinum was 4.6%, comparable to the reported PSPM recurrence rates of 0–4.5% in previous case series studies [4, 6, 13–16]. However, since RSPM was rare disease even more than PSPM, there was few research on cause or related factors of RSPM. Our results showed that the proportion of patients with smoking (72.8% vs. 37.1%, p = 0.010) or asthma (81.8% vs. 39.8%, p < 0.001) was significantly higher in “recurrence” group than “no recurrence” group. However, on multivariate analysis, asthma was the only associated factor with recurrence (mild intermittent/mild persistent asthma, OR = 7.092, p = 0.047; moderate persistent asthma, OR = 8.000, p = 0.011). Asthma exacerbation has been known as one of the most prominent risk factors for PSPM and PSPM has been reported both as a sign of a first asthma attack and as a consequence of an asthma exacerbation. Furthermore, PSPM may be associated with poorly-controlled asthma [17, 18]. Therefore, both the clinical suspicion of asthma when spontaneous pneumomediastinum occurs and that of spontaneous pneumomediastinum when acute chest pain occurs in patients with asthma are essential.

There are some limitations in this study. The main limitation is the small sample size. There were only 11 patients included in the recurrent group. To validate the results that asthma and smoking are significantly associated factors with RSPM, studies involving more RSPM patients are needed. Second, the present study was conducted based on retrospective design, and selection bias could affect the results. Third, since poorly-controlled asthma is known to be associated with spontaneous pneumomediastinum, it may be necessary to check whether asthma is well controlled by medication or not; however, it is difficult to confirm because this clinical information was not accurately recorded in the electronic medical charts. Further research is needed on these areas, and an improved understanding of associated factors with PSPM and RSPM can lead to more efficient management of patients with spontaneous pneumomediastinum.

In conclusion, PSPM is a self-limited and benign disease and specific treatment may not be required if there is not concurrent pneumothorax. Furthermore, patients with asthma should be informed about the chance of recurrence despite the low rate of recurrence, since the asthma may be the associated factor with RSPM.