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Comparing the clinical characteristics and risk factors of prognosis in pediatric ARDS with and without malignancies: a retrospective cohort study

BMC Pulmonary Medicine volume 25, Article number: 136 (2025) Cite this article

Abstract

Background

The number of malignancy patients with respiratory failure is rising in pediatric intensive care units (PICU). Our study aims to compare the clinical characteristics and prognostic risk factors of acute respiratory distress syndrome (ARDS) with or without malignancies.

Methods

This retrospective study reviewed medical records of 188 ARDS patients admitted to the PICU between January 2018 and December 2022, including 60 with malignancies and 128 without. Clinical data were collected within 48 h post-ARDS diagnosis. Multivariate logistic regression analysis and receiver operating characteristic curve (ROC) analysis were used to investigate the risk factors for PICU mortality in the malignancy and non-malignancy groups.

Results

Compared with pediatric patients without malignancy, the ARDS patients with malignancy presented higher mortality (55.0% vs. 31.3%, P = 0.002), a higher incidence of community-acquired fungal infection (36.1% vs. 6.3%, P < 0.001) and multidrug resistance (MDR) bacteria (65.4% vs. 30.5%, P = 0.003). There were substantial differences in levels of lactate [1.5 (0.8–3.7) vs. 1.0 (0.7-2.0) mmol/L, P = 0.008], C-reactive protein (CRP) [150.0 (83.0-168.0) vs. 31.0 (10.0-108.0) mg/L, P = 0.02], procalcitonin (PCT) [10.4 (2.0-27.5) vs. 1.2 (0.3–6.2) mg/L, P < 0.001], counts of platelet [17.0 (8.0–73.0) vs. 232.0 (152.0-330.0) × 109/µL, P < 0.001], the distribution of CD8 + T [36.9 (26.0-53.6) vs. 21.9 (17.3–29.1) %, P < 0.001], CD19 + T cells [9.9 (0.9–30.2) vs. 33.6 (22-46.6) %, P < 0.001], and higher peak vasoactive–inotropic score (VIS) in ARDS with malignancy [73.0 (20–208) vs. 15.0 (5.0–82.0), P < 0.01]. In multivariable analysis, only VIS independently predicted mortality in ARDS patients with malignancy (OR, 1.011; 95% confidence interval [CI]: 1.003–1.018; P = 0.005). Neither pSOFA scores (OR, 1.249, 95% CI: 0.958–1.628, P = 0.101) nor lactate levels (OR, 1.192, 95% CI: 0.928–1.531, P = 0.170) showed significant associations.

Conclusion

ARDS patients with malignancies exhibited poorer outcomes. VIS is only an independent predictor of mortality in pediatric ARDS patients with malignancies.

Peer Review reports

Background

ARDS significantly complicates the clinical management of patients with malignancies. Individuals with malignancy are 1.57-fold more likely to develop ARDS than those without malignancies [1]. Studies have demonstrated that the etiology of ARDS in this population is predominantly linked to infections, with pneumonia being the most common precipitating factor [2]. Approximately 50% of patients with hematological and solid tumors require ICU admission due to acute respiratory failure [3]. In pediatric cases, the severity and outcome of ARDS are significantly impacted by underlying malignancy, patients with leukemia/lymphoma undergoing induction chemotherapy have been shown to develop severe ARDS, with a mortality rate that remains concerning despite advancements in the use of extracorporeal membrane oxygenation (ECMO) [4]. It reported that hospital mortality rate excess 50% in children with hematological malignancies [5], emphasizing the urgent need to investigate the risk factors for the development of ARDS and improve prognosis for this unique group of patients.

Therapeutic interventions for malignancy, including chemotherapy, radiation, and bone marrow transplantation, can render pediatric patients immunocompromised, increasing their susceptibility to infections and ARDS [6]. Furthermore, the malignancies and treatment-related complications can exacerbate lung damage and affect the outcomes of ARDS [7]. While research has delved into the epidemiology, pathophysiology, and therapeutic strategies for ARDS, few studies have compared the differences between ARDS with and without malignancy, particularly regarding malignancy type, treatment strategy, and immune status. It’s urgent for research to elucidate these differences and to develop targeted management strategies for high-risk patients.

We conducted a retrospective study in pediatric ARDS patients requiring invasive mechanical ventilation (MV) with and without malignancy, compared their clinical characteristics differences, and explored the risk factors for mortality.

Methods

Study design

This is a retrospective study that included patients diagnosed with ARDS who were admitted to the PICU under the supervision of Shanghai Children’s Hospital from January 2018 to December 2022 according to the medical records. This study was approved by the Ethics Committee of Shanghai Children’s Hospital (2024R149-E01). Informed consent was waived owing to the retrospective nature of this study.

Patients

The following were the inclusion criteria: (1) patients aged 1 month to 18 years; (2) those who met the diagnostic criteria for ARDS according to the Berlin definition [8]; and (3) those who received MV. The following were the exclusion criteria: (1) patients with cardiogenic pulmonary edema; (2) patients with lung lesions due to the infiltration of malignancy; and (3) patients hospitalized in PICU for less than 24 h. The patients were divided into two groups based on their underlying conditions: the malignancy and non-malignancy groups.

Outcomes

The primary outcome was PICU mortality. The second outcome was to investigate the risk factors associated with survival status including VIS, laboratory indicators and related parameters monitored during MV including positive end-expiratory pressure (PEEP), peak inspiratory pressure (PIP), dynamic lung compliance (Cdyn).

Data collection

Data were extracted from the electronic medical record system for each patient. We collected data, including age, sex, body mass index, source of admission, causes of ARDS, primary existing malignancy, blood transfusion, status of bone marrow transplant/hematopoietic stem cell transplantation, identified pathogens, PaO2/FiO2 levels, duration of MV, PEEP, PIP, Cdyn, length of PICU stay, length of hospital stay, PICU survival status, comorbidity of patients, continuous renal replacement therapy (CRRT) and ECMO support, and VIS. Disease severity was assessed using pSOFA. Laboratory indicators included CRP, PCT, indicators of inflammatory factors and cellular immunity. Clinical data (except length of PICU stay, length of hospital stay, intubation on the first day of entering PICU, MV days and PICU survival status) and VIS were measured within 48 h following ARDS diagnosis, and the worst values were selected. We defined agranulocytosis as granulocyte counts less than 500/µL [9]. The maximum value was selected for the VIS and calculated according to the following method: VIS = 1 × dobutamine (µg/kg/min) + 1 × dopamine (µg/kg/min) + 100 × norepinephrine (µg/kg/min) + 100 × epinephrine (µg/kg/min) + 10 × milrinone (µg/kg/min) + 10,000 × vasopressin [10]. Community-acquired infection was defined as a pathogen that led to ARDS acquired out of a hospital or within 48 h of hospitalisation [11]. Hospital-acquired infection was defined as an infection acquired following 48 h of hospitalisation [12].

Statistical analyses

To express nonnormally distributed descriptive statistics data, the interquartile range (IQR) was employed; For cases where data were missing, we used the median value of all available data points for each variable to fill in the gaps. To compare continuous variables, Mann–Whitney U tests were performed. To evaluate categorical variables, Fisher’s exact or chi-square test was used. Multivariate logistic regression analysis was used to evaluate the risk factors for PICU mortality in the malignancy and non-malignancy groups. Variables that demonstrated statistically significant differences between survivors and non-survivors in univariate analyses were entered into further multivariate logistic regression analysis, conducted separately for malignancy and non-malignancy patients. To appreciate the accuracy of independent predictors of PICU mortality, the ROC curve and Youden index were generated. Statistical analyses were performed using SPSS 26.0. P values < 0.05 were considered statistically significant.

Results

Characteristics of ARDS patients with and without malignancies

A total of 188 children with moderate-to-severe ARDS were included in this study, of whom 60 had malignancies (Table 1). ARDS patients with malignancy were more likely to be older (median: 79.0 vs. 34.0 months) and have higher pSOFA scores (14.0 vs. 9.0 points) than those without malignancy (all P values < 0.05). Additionally, children with malignancy had a higher PICU mortality rate (55.0% vs. 31.3%, P = 0.002) and shorter length of PICU stay (10.0 vs. 13.0 days, P = 0.019) than those without malignancy.

Table 1 Characteristics of moderate-to-severe ARDS patients grouping based on whether suffering malignancy
Full size table

In this study, 166 (88.3%) of the 188 patients with ARDS were culture-positive for one or more pathogen infections in sputum or bronchoalveolar lavage fluid (Table 1). The pathogen spectrum between patients with and without malignancies was different. For patients with community-acquired pneumonia, bacteria were the most common pathogens overall. However, in patients with malignancies, the second most common pathogens were fungi (36.1%), with Pneumocystis jirovecii and Aspergillus being frequently detected in sputum or alveolar lavage fluid. In contrast, children without malignancies showed viruses as the second most common pathogens (30.5%), with adenoviruses, respiratory syncytial virus, and influenza virus being predominant. In hospital-acquired infections, a shift in pathogen distribution was observed. Gram-negative bacteria, including Acinetobacter baumannii (A. baumannii), Pseudomonas aeruginosa (P. aeruginosa), and Klebsiella pneumoniae, were the most prevalent pathogens in hospital-acquired pneumonia among malignancy patients, with MDR observed in 81.8% of cases (9/11 patients with bacterial infections). Conversely, among patients without malignancies, 13 out of 15 patients were infected with gram-negative bacteria, with a notable prevalence of A. baumannii and P. aeruginosa. This group exhibited a high mortality rate, with 8 of the 9 infected patients (88.9%) succumbing to their infections. Furthermore, when comparing the overall infection rates between hospital-acquired and community-acquired bacterial infections, patients with malignancies had a significantly higher rate of MDR bacteria. Specifically, 65.4% (17/26) of ARDS patients with malignancies were infected with MDR bacteria, compared to 30.5% (18/59) in patients without malignancies (P = 0.003).

Thirty-two (53.3%) patients were diagnosed with agranulocytosis within the first week of PICU stay. According to the different types of malignancy, 47 patients had hematological malignancies, including 25, 16, and 6 patients with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and non-Hodgkin’s lymphoma, respectively. 13.3% of total patients with malignancy experienced recurrence (the patients relapsed before their admission to the PICU) and 18.2% of those with recurrence were dead (Supplemental Fig. 1).

Use of life-supporting interventions in patients with and without malignancies

Patients with ARDS and malignancy had a higher utilization rate of CRRT and a shorter duration of MV times than those without (P < 0.05). Survivors in the malignancy group were linked to lower CRRT use and longer MV durations than those in non-survivors, though not significantly. Survivors without malignancy also showed a non-significant trend towards CRRT use and MV durations. Ventilation parameters were noted between survivors and non-survivors in either group (Table 2).

Table 2 The comparison of clinical treatments between malignancy and non-malignancy patients
Full size table

Characteristic of non-pulmonary organ dysfunction in ARDS patients with and without malignancies

By comparing with ARDS patients with or without malignancies, we observed that although pSOFA scores in the nervous and cardiovascular systems did not differ significantly, they did differ in other non-pulmonary organs. Additionally, we noted that the peak VIS values were elevated in malignant patients as compared to non-malignancy counterparts. Furthermore, pronounced differences were identified between the two groups regarding rate of transfusion of red blood and platelet, levels of haematoglobin, absolute neutrophil count, absolute Platelet counts, lactate, CRP, PCT, as well as the distribution of CD8+ and CD19+ cells.

In patients with malignancy, survivors had lower VIS, pSOFA scores and Lactate levels than non-survivors (all P < 0.05). In patients without malignancy, survivors had lower pSOFA scores, serum CRP, Lactate, and IL-6 levels than non-survivors (all P < 0.05) (Table 3).

Table 3 Characteristics of non-pulmonary organ dysfunction in ARDS patients with or without malignancy
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Survival analysis and risk factor

The Kaplan–Meier curve indicated that the cumulative survival rate in the malignancy group was significantly lower than that in the non-malignancy group (Fig. 1). Using the multivariable logistic regression models, we explored the risk factors for PICU mortality in both patients with and without malignancies, and noted that the VIS (OR, 1.011; 95% CI: 1.003–1.018; P = 0.005) was an independent risk factor for PICU mortality in patients with malignancy (Table 4).

Fig. 1
figure 1

Kaplan–Meier curve of the PICU mortality in patients with and without malignancies

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Table 4 Risk factors associated with PICU mortality in patients with and without malignancy
Full size table

According to the ROC curve of VIS in predicting the survival status in patients with malignancy (Fig. 2a), the area under the curve (AUC) was 0.800 (95% CI: 0.69–0.91, P < 0.05), and the best cutoff value of the VIS was 137.5, with a sensitivity of 0.606, specificity of 0.889, accuracy of 0.733, positive predictive value of 0.870, and negative predictive value of 0.649. The Kaplan–Meier curve and log-rank test (< 0.001) also showed a significant difference in the survival rate between patients with subgroups stratified by the VIS (< 137.5 vs.≥137.5) (Fig. 2b).

Fig. 2
figure 2

VIS is an independent predictor of PICU mortality in patients with malignancy. (a) The receiver operating characteristic curve of the vasoactive–inotropic score (VIS) in predicting the survival status in patients with malignancy. The sensitivity is 0.606, specificity is 0.889, accuracy is 0.733, positive predictive value is 0.870 and negative predictive value is 0.649. (b) the Kaplan–Meier curve of the PICU mortality in the subgroups stratified by the VIS (cutoff value, 137.5) in patients with malignancy

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Discussion

Our study found that ARDS with malignancy children had a significantly higher risk of death than those without malignancy. Children with malignancy who develop ARDS are more prone to complications, including community-acquired fungal infection, MDR bacterial infection, and organ dysfunction. To the best of our knowledge, this is the first research report comparing mortality rates and clinical characteristics between ARDS patients with and without malignancy in a large-scale PICU population in China. The populations with compromised immune systems, especially those with malignancy, are more susceptible to infections and drug resistance [13,14,15]. MDR infections not only prolong the hospital stay and intensive care requirements for malignancy patients but also significantly increase mortality [2]. In the case of ARDS, MDR infections worsen clinical outcomes, especially in immunosuppressed patients [16]. Study have shown that that patients with malignancy are prone to infections, particularly those caused by drug-resistant pathogens, after undergoing immunosuppressive treatments such as chemotherapy and radiotherapy [17]. A large retrospective study found that approximately 90% of ARDS cases in patients with malignancy were related to infections, with a significant portion caused by invasive fungal infections [2]. Moreover, the immunosuppressed state following chemotherapy significantly reduces these patients’ resistance to infections, leading to an increased incidence of MDR infections [18]. MDR infections often present atypically, which may delay diagnosis and treatment, increasing risks for patients [19]. Therefore, early identification and proactive management of these infections are key to improving outcomes. Future research should focus on optimizing these patients’ management strategies to reduce the worsened outcome of MDR infections.

In present cohort study, we found that children with malignancy have a significantly higher incidence of organ dysfunction compared to non-malignancy patients. Consistent with previous reports, malignancy is more likely to impair the lungs, liver, kidneys, and coagulation functions, thereby directly impacting patients’ overall quality of life and prognosis [20]. Malignancy patients in our PICU have lower hemoglobin and platelet levels compared to non-malignancy patients, leading to a greater need for blood transfusions. This further reflects the fragility of their hematological system. The frequency of CRRT use in ARDS patients with malignancies has significantly increased in our center, possibly due to the more widespread occurrence of kidney or liver dysfunction in this particular population. Furthermore, CRRT can effectively correct metabolic imbalances, study in pediatric malignancy patients found that CRRT has a rapid effect in correcting hyperphosphatemia and hyperuricemia in tumor lysis syndrome. Most patients returning to normal electrolyte levels within 12 h after CRRT initiation [21]. Moreover, a retrospective study involving patients with AKI and malignancy revealed that the overall mortality rate remains alarmingly high, particularly among those with hematological malignancies [22]. Factors such as the timing of CRRT initiation, severity of illness as indicated by the SOFA score, and the presence of oliguria were significant predictors of outcomes in this population [23, 24]. Notably, early initiation of CRRT has been correlated with improved survival rates [25]; emphasizing the importance of timely intervention in critically ill patients.

In our study, children with malignancy had a shorter duration of ventilation than their non-malignancy counterparts. This difference may be closely linked to the higher mortality risk that malignancy patients experience in the PICU. Additionally, evidence indicates that non-invasive ventilation can effectively lower mortality rates in patients with hematological malignancies compared to invasive mechanical ventilation [26]. The literature has also validated the effectiveness of non-invasive ventilation in pediatric immunocompromised patients [27]. This further emphasizes the importance of minimizing the reliance on invasive support for this vulnerable population. Unfortunately, our study did not track ventilator-free days, leading to missing data that limits our ability to conduct an in-depth analysis of the potential benefits of non-invasive ventilation. The variables of CRP and PCT levels and the distribution of CD8+ T cells and CD19+ B cells indicate unique infection and immune response characteristics in patients with malignancies. This immune characteristic may reflect the complexity of the tumor microenvironment and the tumor cells’ escape mechanisms from the host immune system. Immune system in malignancy patients is often in a state of continuous activation, leading to immune suppression and increased risk of infection, which can adverse outcomes [28]. Therefore, monitoring immune status of malignancy patients will help optimize treatment plans and improve patient prognosis. Identifying VIS as a risk factor for mortality in ARDS patients with malignancies represents a pivotal finding in our research. Elevated VIS levels are typically associated with hemodynamic instability in patients, which is particularly pronounced in those with malignancy, the presence of malignancy affects the patient’s physiological state and can cause hemodynamic changes during treatment, potentially worsening the condition and increasing mortality risk [29]. Previous research has demonstrated that VIS is highly sensitive and specific in predicting mortality in PICU [30]. For instance, one study showed a significant correlation between VIS and mortality risk in patients with septic shock, with an AUC of 0.88, further validating the effectiveness of VIS as a prognostic indicator [31]. Additionally, higher VIS levels are linked to organ dysfunction and increased mortality, highlighting the importance of VIS in guiding clinical management [32, 33]. In patients with malignancy, a higher VIS likely reflect the hemodynamic changes caused by the malignancy and its treatment; for instance, a study of pediatric patients with hematological malignancies found a positive correlation between high VIS and mortality [5]. Moreover, prolonged mechanical ventilation time and higher VIS may impact the prognosis of children with hemophagocytic lymphohistiocytosis, further emphasizing the necessity of monitoring VIS in clinical practice [34]. In summary, as an independent prognostic indicator, VIS holds broad application prospects in ARDS with malignancy. Clinicians should consider incorporating it into routine monitoring to better assess changes in the patient’s condition and optimise treatment strategies.

Our study has several limitations. Firstly, as a single-center, limited-scale retrospective study, its conclusions need to be confirmed by a multi-center, well-designed, and prospective study with a larger population. Secondly, the lack of data on ventilator-free days hampers a comprehensive assessment of patients’ respiratory support needs and recovery times. Lastly, due to limitations in data collection, we could not include information on MDR genes in this study.

Conclusion

ARDS patients with malignancies present higher mortality rates and more organ dysfunction than those without malignancies. The VIS only serves as an independent predictor of mortality in ARDS patients with malignancy.

Data availability

The datasets used or analyzed during the current study are available from the corresponding author upon reasonable request.

Abbreviations

ALL:

Acute lymphoblastic leukemia

AML:

Acute myeloid leukemia

ARDS:

Acute respiratory distress syndrome

AUC:

The area under the curve

BMT:

Bone marrow transplantation

Cdyn:

Dynamic lung compliance

CRP:

C-reactive protein

CRRT:

Continuous renal replacement therapy

CI:

Confidence interval

ECMO:

Extracorporeal membrane oxygenation

HSCT:

Hematopoietic stem cell transplantation

OR:

Odds ratio

IFN-γ:

Interferon-γ

IL-6:

Interlukin-6

IL-8:

Interlukin-8

IQR:

The interquartile range

MDR:

Multidrug resistance

MV:

Mechanical ventilation

PCT:

Procalcitonin

PEEP:

Positive end-expiratory pressure

PICU:

Pediatric intensive care unit

PIP:

Peak inspiratory pressure

pSOFA:

Pediatric sequential organ failure assessment score

ROC:

Curve, receiver operating characteristic curve

TNF-α:

Tumor necrosis factor alpha

VIS:

Vasoactive–inotropic score

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Acknowledgements

Not applicable.

Funding

Financial support was provided by Shanghai Municipal Health Commission Special Project for Clinical Research in the Healthcare Industry (20244Y0020). the National Natural Science Foundation of China (82100085). the Science and Technology Commission of Shanghai Municipality (18411951000). the National Key Research and Development Program of China (2021YFC2701800, 2021YFC2701805).

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Authors and Affiliations

  1. Department of Critical Care Medicine, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200062, China

    Xi Xiong, Yun Cui, Chunxia Wang, Yiping Zhou, Xiaoxuan Ma & Yucai Zhang

  2. Laboratory of Critical Care Translational Medicine, Institute of Pediatric Infection, Immunity, and Critical Care Medicine, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200062, China

    Xi Xiong, Yun Cui, Chunxia Wang & Yucai Zhang

  3. Institute of Pediatric Critical Care, Shanghai Jiao Tong University, Shanghai, 200062, China

    Xi Xiong, Yun Cui, Chunxia Wang & Yucai Zhang

  4. Department of Endocrinology, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200062, China

    Pin Li

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  5. Xiaoxuan Ma
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  6. Pin Li
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  7. Yucai Zhang
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Contributions

Yucai Zhang designed and supervised the research. Pin Li provided guidance and helped construct the article’s framework. Xi Xiong, Xiaoxuan Ma and Yiping Zhou collected clinical data. Xi Xiong and Xiaoxuan Ma analyzed the data. Xi Xiong wrote the manuscript. Pin Li, Yun Cui, Yucai Zhang and Chunxia Wang reviewed and edited the manuscript. All authors contributed to the work and approved it for publication. Yucai Zhang is the guarantor of this research and takes responsibility for the integrity and accuracy of the work.

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Correspondence to Pin Li or Yucai Zhang.

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This study was approved by the Ethics Committee of Shanghai Children’s Hospital (2024R149- E01). Informed consent was waived because of the retrospective nature of the study.

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Not applicable.

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The authors declare no competing interests.

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Supplementary Material 1

: Supplemental Fig. 1. Type and clinical characteristics of ARDS patients with malignancy depending on PICU mortality. (a) Different types of malignancy, (b) disease status of malignancy, (c) agranulocytosis and BMT/HSCT of ARDS patients with malignancy. *, indicates P < 0.05, ns, indicates P > 0.05. Abbreviations: ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; BMT, bone marrow transplantation; HSCT, hematopoietic stem cell transplantation. a Other malignancies including Hodgkin’s lymphoma, chronic myeloid leukemia, myelodysplastic syndromes, and chronic eosinophilic leukemia

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Xiong, X., Cui, Y., Wang, C. et al. Comparing the clinical characteristics and risk factors of prognosis in pediatric ARDS with and without malignancies: a retrospective cohort study. BMC Pulm Med 25, 136 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12890-025-03598-w

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  • DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12890-025-03598-w

Keywords

BMC Pulmonary Medicine

ISSN: 1471-2466

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