Risk factors and age-specific monthly patterns of primary spontaneous pneumothorax: a multicenter study

Introduction

Background

Primary spontaneous pneumothorax (PSP) is characterized by the sudden collapse of the lung without external damage in individuals without underlying lung disease. It occurs when air enters the pleural space, leading to partial or complete lung collapse and causing sharp chest pain and breathlessness. Despite its potential severity, research on PSP occurrence and recurrence is limited, partly due to its low prevalence. Existing studies indicate varying incidence rates among female, 1.2 to 6 per 100,000, and male patients, 7.4 to 18.0 per 100,000 (1).

Rationale and knowledge gap

The recurrent nature of PSP poses significant health risks and underscores the need for comprehensive research into its underlying causes and mechanisms (2). Although previous literature provides insights into recurrence rates and potential risk factors, a comprehensive analysis is lacking (3-8). Addressing this gap is crucial for identifying modifiable risk factors and developing targeted interventions to mitigate recurrence rates.

Objective

Therefore, this study aimed to explore the epidemiology of pneumothorax in Korea, including monthly incidence patterns by age group and investigate hemodynamic indicators affecting recurrence. These findings may help identify specific environmental and physiological factors contributing to PSP. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2024-1957/rc).

Methods

Patient selection

We conducted a retrospective analysis of data from five university hospitals affiliated to The Catholic University of Korea (Seoul St. Mary’s Hospital, St. Vincent’s Hospital, Incheon St. Mary’s Hospital, Bucheon St. Mary’s Hospital, and Uijeongbu St. Mary’s Hospital) covering the period from January 2013 to May 2023. Among 12,828 patients diagnosed with pneumothorax, 4,231 met the inclusion criteria. Patients under 10 or over 39 years of age; those with missing clinical data; and those with traumatic or secondary spontaneous pneumothorax (SSP) were excluded from the study. Subgroup analyses were performed based on age (teenagers and ≥20 years) and sex (Figure 1).

Figure 1 Flow diagram of patient inclusion in the study.

Variables definitions

Pneumothorax classification included spontaneous pneumothorax (SP) and traumatic pneumothorax, with SP further categorized into PSP and SSP related to underlying lung disease (9). Patients under 40 years old without secondary pneumothorax were included in the study.

To assess month-based occurrence patterns, we captured the month of the first emergency department visit or hospitalization with a diagnosis of pneumothorax. Month-based patterns were also analyzed for the time of first recurrence, defined as an emergency department visit or hospitalization for the same diagnosis.

Height and weight data within one year of diagnosis were used to calculate body mass index (BMI), categorized according to World Health Organization criteria. Lean body type was defined as BMI <18.5 kg/m².

Laboratory data included complete blood count, hemoglobin, hematocrit, platelet, and white blood cell counts. The percentage of each inflammatory cell (neutrophil, lymphocyte, monocytes, eosinophils, and basophils) was also analyzed. The levels of albumin, aspartate transaminase, and alanine transferase, indicative of the nutritional status, were also analyzed. Creatine phosphokinase levels were used as an indicator of muscle damage or stress.

Statistical analysis

Continuous variables were analyzed using the independent t-test, while categorical variables were examined using the Chi-squared and Fisher’s exact tests. Descriptive statistics are represented as means and standard deviations for continuous variables and frequencies and percentages for categorical variables. The Shapiro-Wilk test assessed the normality of each parameter’s distribution. Logistic regression analysis was performed to identify factors contributing to recurrence, including age, sex, smoking status, BMI, and laboratory results (white blood cell, hemoglobin, hematocrit, platelet). Statistical analyses were performed using R (v4.2.2; R Core Team 2022, Vienna, Austria), with a package including moon Book. A P value <0.05 indicated statistical significance.

Ethical statement

This study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Institutional Review Board of The Catholic University of Korea (No. KC23WIDI0546), and individual consent for this retrospective analysis was waived.

Results

Patient characteristics

Among the 4,231 patients, 3,596 (85.0%) were male and 635 (15.0%) were female patients, with a male-to-female ratio of 5.7:1. Of the male patients, 1,884 (52.4%) were teenagers and 1,712 (47.6%) were over 20 years of age. Among female patients, 195 (30.0%) were teenagers and 440 (70.0%) were over 20 years of age. Additionally, 1,203 (33.5%) male and 256 (40.3%) female patients had a BMI <18.5 kg/m². The number of recurrences was 1,591 and 254 in male and female participants, with recurrence rates of 44.2% and 40.0%, respectively; the differences in these rates were marginally significant (P=0.052) (Table 1). The peak age at first diagnosis was 18 years (12.24%), followed by 17 years (11.51%), 16 years (8.70%), and 19 years (8.04%) (Figures 2,3). Subgroup analysis in patients aged 16–19 years revealed less tobacco use, and highly lean body compared with the general population. The recurrence rate in the age group of 16–19 years was comparable between the sexes at 778 (49.4%) male and 66 (47.5%) female cases (Table 2).

Figure 2 Distribution of patients first diagnosed with PSP by sex and age (years). PSP, primary spontaneous pneumothorax.

Figure 3 Proportion of patients first diagnosed with PSP by age group (years). PSP, primary spontaneous pneumothorax.

Monthly prevalence

July (n=209, 10.05%) was the most common diagnosis month in teenagers, followed by October (n=195, 9.38%) and March (n=193, 9.28%). The lowest incidence month was February (n=132, 6.35%). There was a statistically significant difference in occurrence between each month (P=0.001). Although the timing of first pneumothorax diagnosis did not differ by month, November (n=199, 9.25%) and August (n=160, 7.43%) were the most and least common diagnosis months in patients aged ≥20 years (P=0.64) (Figure 4A,4B). Regarding the timing of first recurrence, teens showed higher rates during March–April (n=199, 19.15%) and July–August (n=195, 18.76%) (P=0.17), whereas patients aged ≥20 years reported a recurrence peak in March (n=81, 10.05%) (P=0.55) (Figure 5A,5B).

Figure 4 Monthly prevalence of the first diagnosis of PSP in (A) teenage patients and (B) those in their 20–30s. PSP, primary spontaneous pneumothorax.

Figure 5 Monthly prevalence of the first recurrence of PSP in (A) teenage patients and (B) those in their 20–30s. PSP, primary spontaneous pneumothorax.

Risk factors for PSP first recurrence

Using multivariate analysis, BMI at initial diagnosis was a significant risk factor for first recurrence in male patients aged 16–19 years [hazard ratio (HR), 0.98; 95% confidence interval (CI): 0.97–0.99; P=0.001] (Table 3) and in those aged ≥20 years (HR, 0.99; 95% CI: 0.98–0.99; P<0.001). In male patients aged ≥20 years, monocyte-lymphocyte ratio (MLR) at initial diagnosis was also a significant factor for first pneumothorax recurrence (HR, 1.20; 95% CI: 1.10–1.32; P<0.001) (Table 4). In female patients aged ≥20 years, MLR was significantly linked to first pneumothorax recurrence (HR, 1.41; 95% CI: 1.07–1.87; P=0.01), whereas BMI was not associated with it (Table 4).

Discussion

Key findings

Our study, encompassing a substantial patient cohort, underscores the concentration of PSP incidence among late teens in Korea. Notably, this study provided a deeper analysis of age at onset compared with previous studies (2,10,11), showing different monthly dynamics in the incidence of PSP among individuals aged 20 years and older versus teens. However, no statistically significant differences were identified, providing nuanced directions for future investigation. Additionally, we identified BMI and MLR as risk factors for PSP recurrence: BMI was a male sex-specific factor, whereas MLR applied to both sexes.

Strengths and limitations

Our study provides significant insights based on month-based pneumothorax epidemiology analysis in Korea, which has not been extensively explored in prior research. The study has some limitations. First, there might be selection bias inherent in its retrospective design. Although it comprised data from five multicenter studies, the inclusion of only a few regions in Korea limits its ability to represent nationwide trends. Additionally, being retrospective and reliant on a database, the diagnosis used in the search was pneumothorax rather than PSP, potentially introducing misclassifications. Despite exerting efforts to minimize errors by excluding traumatic pneumothorax and SSP through medical record reviews and age restrictions, some misclassifications, such as undiagnosed Birt-Hogg-Dubé syndrome or menstrual-related pneumothorax, might have remained. These conditions are relatively rare and often underreported in medical records, particularly in retrospective studies. However, given their low prevalence and the careful application of inclusion criteria, the impact on our findings is likely minimal. Furthermore, due to the retrospective nature of the study, we were unable to include treatments performed at the time of the initial pneumothorax in the risk factor analysis. Specifically, the presence or absence of surgical intervention is considered an important factor associated with recurrence rates. However, given that current guidelines generally recommend avoiding surgical intervention during the first episode of pneumothorax (except for cases such as tension pneumothorax or in patients with specific occupational requirements) (12); it is likely that very few patients in our cohort underwent surgery during their initial episode. Therefore, we suggest that this limitation had minimal impact on the study’s overall findings. Second, this study did not assess subpleural bullae or apex dysplasia, significant factors in juvenile PSP, due to limitations in retrospective medical records. Future prospective studies should address this. Third, potential biases in our study, including age-specific factors influencing recurrence risk, warrant further prospective investigations to better understand these dynamics and validate our findings. Fourth, we found no statistically significant differences in monthly incidence and recurrence pattern by age group. However, we suggest that it is significant that the occurrence of pneumothorax requires consideration of various factors. Some laboratory markers were excluded from risk factor analysis due to missing data. Nevertheless, teenagers and other age groups have different characteristics in terms of risk factors as well as epidemiology, suggesting that factors unique to teenagers might be important factors for pneumothorax. Therefore, further studies will be important for characterizing pneumothorax.

Explanation of findings and comparison with results in similar research

The heightened incidence of pneumothorax in late teenage years may stem from apex stress induced by a low thoracic index during post-adolescent adult size attainment, as posited by Casha et al. (13). The observed disparity in monthly incidence dynamics, particularly among late teens, may stem from environmental factors. Lee et al. suggested that perceived stress could influence pneumothorax incidence, potentially exacerbated by academic pressures during this developmental stage (14). Furthermore, factors such as air pollutants and airborne infections, prevalent in densely populated school environments, may contribute to pneumothorax risk (15). Although previous studies that analyzed monthly incidence rates have shown similar patterns of seasonal frequency of occurrence, they were limited by small sample sizes, which may have obscured some of these patterns (16,17). Therefore, further larger-scale research is essential for clarifying the relationship between environmental factors and pneumothorax.

Prior research has established the association of BMI with pneumothorax development (16,18,19), with low BMI being a recognized risk factor for PSP recurrence (20,21). Our study also shows that the proportion of patients with lean bodies was high in both sexes. Conversely, the proportion of patients with a BMI of 25 or higher in both sexes was approximately 5% (6.4% in men and 4.9% in women), which is quite low compared with this proportion in the Korean population as a whole (33.1% in the under 19 years age group, 31.1% in the 19–29 years age group, and 39.8% in the 30–39 years age group) (22,23), suggesting a significant correlation between body mass and the occurrence of pneumothorax. However, the substantial representation of patients within the 18.5–23 kg/m² BMI range, considered normal, implies that BMI alone might not fully explain pneumothorax occurrence. Dynamic changes in body shape, particularly rapid height growth followed by volume increase, as proposed by Casha et al. could contribute to pneumothorax incidence (13). Therefore, a comprehensive analysis of growth patterns over time is warranted to elucidate the association between pneumothorax and BMI.

Risk factor analysis revealed BMI as a significant contributor to recurrence rates in teenage male and in male patients aged ≥20 years, supporting the impact of body mass on PSP recurrence. Additionally, the MLR value at the time of initial diagnosis emerged as a significant factor. Meanwhile, in female patients aged 16–19 years, neither BMI nor MLR was a risk factor. However, the sample size was small, potentially accounting for the undetected effect.

Our study sheds light on the impact of various hematologic markers as risk factors for first recurrence after initial pneumothorax, highlighting the significance of MLR (7). Saricam et al. suggested an association between lymphocyte-monocyte ratio and SP recurrence; meanwhile, our study contributes evidence based on a larger sample size and multivariate analysis, encompassing additional relevant laboratory markers (24). The pathophysiology of pneumothorax, traditionally attributed to emphysema-like changes in the visceral pleura, has recently been linked to inflammation-induced diffuse porosity, which could be its key mechanism (8,25). MLR indicates an interaction between innate and adaptive immune reactions (26,27). Increased levels of MLR can heighten systemic inflammation levels and disrupt immune regulation (27,28). Chronic inflammation leads to sustained production of pro-inflammatory cytokines, which recruit more monocytes and inhibit lymphocyte proliferation and function. This imbalance contributes to an increased MLR (29). Previous studies have demonstrated microscopic evidence of respiratory bronchiolitis characterized by accumulation of macrophages differentiating from monocytes in some patients undergoing surgery for PSP, which may suggest that monocytes are associated with pneumothorax (8,25,30).

Implications and actions needed

Our findings support the notion that inflammatory status influences recurrence, with the MLR value serving as a meaningful surrogate marker in this regard. However, potential biases in our study warrant further prospective investigations to validate these findings.

Conclusions

Our findings revealed distinct incidence patterns among teenagers compared with those in other age groups, warranting further investigation. Furthermore, our findings linking BMI and inflammation status to pneumothorax recurrence offer valuable groundwork for future prospective studies aimed to prevent and establish effective treatment strategies.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2024-1957/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2024-1957/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2024-1957/prf

Funding: This study was supported by the Research Fund of Seoul St. Mary’s Hospital, The Catholic University of Korea (No. ZC23RAMI0916).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2024-1957/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Institutional Review Board of The Catholic University of Korea (No. KC23WIDI0546), and individual consent for this retrospective analysis was waived.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Mitani A, Hakamata Y, Hosoi M, et al. The incidence and risk factors of asymptomatic primary spontaneous pneumothorax detected during health check-ups. BMC Pulm Med 2017;17:177. [Crossref] [PubMed]
2. Kim D, Jung B, Jang BH, et al. Epidemiology and medical service use for spontaneous pneumothorax: a 12-year study using nationwide cohort data in Korea. BMJ Open 2019;9:e028624. [Crossref] [PubMed]
3. Ghisalberti M, Guerrera F, De Vico A, et al. Age and Clinical Presentation for Primary Spontaneous Pneumothorax. Heart Lung Circ 2020;29:1648-55. [Crossref] [PubMed]
4. Fujiwara T, Tanaka K, Toyoda T, et al. Risk factors of postoperative recurrence of primary spontaneous pneumothorax. J Thorac Dis 2020;12:6458-65. [Crossref] [PubMed]
5. Udelsman BV, Chang DC, Lanuti M, et al. Risk factors for recurrent spontaneous pneumothorax: A population level analysis. Am J Surg 2022;223:404-9. [Crossref] [PubMed]
6. Akkas Y, Peri NG, Kocer B, et al. A novel structural risk index for primary spontaneous pneumothorax: Ankara Numune Risk Index. Asian J Surg 2017;40:249-53. [Crossref] [PubMed]
7. Luo X, Wan D, Xia R, et al. Prognostic Value of the Baseline and Early Changes in Monocyte-to-Lymphocyte Ratio for Short-Term Mortality among Critically Ill Patients with Acute Kidney Injury. J Clin Med 2023;12:7353. [Crossref] [PubMed]
8. Plojoux J, Froudarakis M, Janssens JP, et al. New insights and improved strategies for the management of primary spontaneous pneumothorax. Clin Respir J 2019;13:195-201. [Crossref] [PubMed]
9. Shields TW. General Thoracic Surgery. 7th ed. Philadelphia: Lippincott Williams & Wilkins; 2009.
10. Hallifax RJ, Goldacre R, Landray MJ, et al. Trends in the Incidence and Recurrence of Inpatient-Treated Spontaneous Pneumothorax, 1968-2016. JAMA 2018;320:1471-80. [Crossref] [PubMed]
11. Sadikot RT, Greene T, Meadows K, et al. Recurrence of primary spontaneous pneumothorax. Thorax 1997;52:805-9. [Crossref] [PubMed]
12. Roberts ME, Rahman NM, Maskell NA, et al. British Thoracic Society Guideline for pleural disease. Thorax 2023;78:s1-s42. [Crossref] [PubMed]
13. Casha AR, Manché A, Gatt R, et al. Is there a biomechanical cause for spontaneous pneumothorax? Eur J Cardiothorac Surg 2014;45:1011-6. [Crossref] [PubMed]
14. Lee SH, Choi H, Kim S, et al. Association between anger and first-onset primary spontaneous pneumothorax. Gen Hosp Psychiatry 2008;30:331-6. [Crossref] [PubMed]
15. Wang S, Li J, Qian M, et al. Excessive aggregation of fine particles may play a crucial role in adolescent spontaneous pneumothorax pathogenesis. PeerJ 2023;11:e16484. [Crossref] [PubMed]
16. Gu BM, Ko HH, Ra YJ, et al. Correlation of Primary Spontaneous Pneumothorax and Air Pollution in Adolescents. J Chest Surg 2021;54:53-8. [Crossref] [PubMed]
17. Lee SJ, Cha MA, Woo YR, et al. Clinical characteristics of primary spontaneous pneumothorax in adolescents: factors for recurrence. Allergy Asthma Respir Dis 2014;2:251-8.
18. Tschopp JM, Bintcliffe O, Astoul P, et al. ERS task force statement: diagnosis and treatment of primary spontaneous pneumothorax. Eur Respir J 2015;46:321-35. [Crossref] [PubMed]
19. Smyth R, Shojaee S, Feller-Kopman D. Primary Spontaneous Pneumothorax. N Engl J Med 2024;390:666-8. [Crossref] [PubMed]
20. Walker SP, Bibby AC, Halford P, et al. Recurrence rates in primary spontaneous pneumothorax: a systematic review and meta-analysis. Eur Respir J 2018;52:1800864. [Crossref] [PubMed]
21. Tan J, Yang Y, Zhong J, et al. Association Between BMI and Recurrence of Primary Spontaneous Pneumothorax. World J Surg 2017;41:1274-80. [Crossref] [PubMed]
22. Statistics Korea. Body mass index distribution by age. 2024. Available online: https://kosis.kr/statHtml/statHtml.do?orgId=350&tblId=DT_35007_N057&conn_path=I2
23. Statistics Korea. Obesity prevalence: Korea National Health & Nutrition Examination Survey. 2024. Available online: https://kosis.kr/statHtml/statHtml.do?orgId=177&tblId=DT_11702_N101&conn_path=I2
24. Saricam M, Guven O, Ozkan B. Utilizing the lymphocyte-monocyte ratio in predicting the recurrence of spontaneous pneumothorax. Cir Cir 2023;91:725-9. [Crossref] [PubMed]
25. Hallifax R. Aetiology of Primary Spontaneous Pneumothorax. J Clin Med 2022;11:490. [Crossref] [PubMed]
26. Iwasaki A, Medzhitov R. Regulation of adaptive immunity by the innate immune system. Science 2010;327:291-5. [Crossref] [PubMed]
27. Ke J, Qiu F, Fan W, et al. Associations of complete blood cell count-derived inflammatory biomarkers with asthma and mortality in adults: a population-based study. Front Immunol 2023;14:1205687. [Crossref] [PubMed]
28. Nagy N, Kuipers HF, Marshall PL, et al. Hyaluronan in immune dysregulation and autoimmune diseases. Matrix Biol 2019;78-79:292-313. [Crossref] [PubMed]
29. Sari DI, Wardhani P, Yessy Puspitasari NIM, et al. Association of monocyte-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio, and tumor necrosis factor-α in various stages of chronic kidney disease. J Adv Biotechnol Exp Ther 2024;7:346-56.
30. Wilson PM, Rymeski B, Xu X, et al. An evidence-based review of primary spontaneous pneumothorax in the adolescent population. J Am Coll Emerg Physicians Open 2021;2:e12449. [Crossref] [PubMed]