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The impact of chronic obstructive pulmonary disease on the risk of immune-related pneumonitis in lung cancer patients undergoing immunotherapy: a systematic review and meta-analysis

BMC Pulmonary Medicine volume 24, Article number: 393 (2024) Cite this article

Abstract

Background

Lung cancer, a leading cause of cancer mortality, poses significant treatment challenges. The use of immune checkpoint inhibitors (ICIs) has revolutionized therapy, but it is associated with immune-related pneumonitis (IRP). This study systematically reviews and analyzes the impact of Chronic Obstructive Pulmonary Disease (COPD) on the risk of IRP in lung cancer patients undergoing immunotherapy.

Methods

Adhering to PRISMA guidelines and using the PICO framework, a comprehensive search across PubMed, Embase, Web of Science, and the Cochrane Library was conducted. Inclusion criteria encompassed peer-reviewed studies involving lung cancer patients treated with ICIs, comparing those with and without COPD. The primary outcome was the incidence and risk of IRP. The Newcastle-Ottawa Scale evaluated study quality. The effect size was calculated using random or fixed-effects models based on the observed heterogeneity. We assessed the heterogeneity between studies and conducted a sensitivity analysis.

Results

The search identified 1026 articles, with six meeting the criteria for inclusion. Studies varied in design and geography, predominantly retrospective cohort studies. Patients with COPD had an increased risk of IRP (OR = 1.54, 95% CI [1.24, 1.92, P < 0.01). Subgroup analysis based on radiation therapy exposure (< 40% and ≥ 40%) also indicated a heightened IRP risk in COPD patients. Sensitivity analysis affirmed the robustness of the results, and publication bias was not significant.

Conclusions

Lung cancer patients with COPD undergoing immunotherapy have a significantly increased risk of developing IRP. This highlights the necessity for vigilant monitoring and individualized treatment strategies to improve the safety and effectiveness of immunotherapy in this group.

Peer Review reports

Introduction

Lung cancer, globally recognized as a leading cause of cancer-related mortality, continues to pose significant healthcare challenges due to its complex etiology and varied prognostic outcomes [1]. The advent of targeted therapies, particularly immune checkpoint inhibitors (ICIs), has marked a paradigm shift in the treatment landscape for lung cancer, offering renewed hope to patients. These novel agents, by modulating the immune system to recognize and combat cancer cells, have shown remarkable efficacy in improving survival rates and enhancing the quality of life in lung cancer patients [2, 3].

ICIs, functioning primarily by inhibiting the interaction between PD-1/PD-L1 or CTLA-4 and their ligands, have redefined oncological treatment protocols. They have been particularly effective in non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), showing prolonged survival in various clinical trials. However, the enthusiasm for these therapies is tempered by the emergence of unique toxicities known as immune-related adverse events (irAEs), which represent a new spectrum of treatment-related complications [4, 5]. Among irAEs, immune-related pneumonitis (IRP) is of particular concern, especially in lung cancer patients. Although relatively infrequent, IRP poses a significant risk due to its potential severity, which ranges from mild, manageable symptoms to life-threatening respiratory failure [6]. Notably, the incidence of IRP is higher in lung cancer populations, possibly due to the pre-existing lung pathology inherent to the disease. This elevated risk underscores the importance of understanding and managing IRP in the context of lung cancer treatment with ICIs [7].

Chronic Obstructive Pulmonary Disease (COPD), a prevalent respiratory condition characterized by persistent respiratory symptoms and airflow limitation, is a heterogeneous disorder comprising various phenotypes including emphysema and chronic bronchitis [8, 9]. The overlap between COPD and lung cancer is considerable, with shared risk factors like smoking and environmental exposures leading to chronic inflammation and cellular changes conducive to cancer development [10]. These complexities make COPD a critical factor in the lung cancer patient population, especially concerning the management of IRP with ICIs. The pathogenesis of COPD involves chronic airway inflammation, structural changes, and a significant alteration in pulmonary immune responses. These factors potentially predispose COPD patients to a heightened risk of IRP when treated with ICIs, due to an already compromised pulmonary system [11]. Despite this plausible association, there is a paucity of robust evidence substantiating COPD as a definitive risk factor for IRP. This gap in knowledge necessitates a thorough investigation into the interrelationship between COPD and IRP, particularly in the context of lung cancer treatment.

The purpose of this study is to systematically review and analyze existing literature to determine the impact of COPD on the risk of developing IRP in lung cancer patients undergoing immunotherapy. This research aims to provide a comprehensive understanding of whether COPD is a significant risk factor for IRP, thereby guiding clinical decision-making in the management of lung cancer patients with pre-existing COPD receiving ICIs. By aggregating and synthesizing data from multiple studies, this meta-analysis seeks to offer a clearer perspective on the interaction between COPD and IRP, contributing valuable insights to the field of oncology and respiratory medicine.

Materials and methods

Search strategy

Throughout the conduct of this systematic review and the ensuing synthesis of our findings, we rigorously adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [12]. Our meta-analysis was methodically structured utilizing the PICO (Patient, Intervention, Comparison, Outcome) framework, which outlined the following dimensions: Patient (P), encompassing individuals diagnosed with lung cancer; Intervention (I), focusing on the use of ICIs as the primary therapeutic approach for lung cancer; Comparison (C), involving a comparative analysis between lung cancer patients afflicted with COPD and those without this condition; and Outcome (O), concentrating on the assessment of the risk and prevalence of IRP within these cohorts.

To ensure a comprehensive literature search, we accessed four major electronic databases: PubMed, Embase, Web of Science, and the Cochrane Library, on September 26, 2023, without imposing any temporal restrictions. Our search strategy incorporated a selection of key terms, namely “lung cancer,” “chronic obstructive pulmonary disease,” “COPD,” “immune checkpoint inhibitors,” “immunotherapy,” “immune-related pneumonitis,” “IRP,” “risk,” “incidence,” and “adverse events.” These terms were meticulously chosen to align with the extensive PICO framework and to guarantee the exhaustive acquisition of pertinent studies for the meta-analysis. We did not apply any language constraints. Additionally, we manually scrutinized the reference lists of pertinent articles to identify any further relevant records (Table S1. Detailed Search Strategy for Systematic Review and Meta-Analysis). We consulted with a medical librarian to develop this search strategy, ensuring thoroughness and relevance. Additionally, we reviewed conference proceedings and engaged with subject matter experts in pulmonary oncology to cover studies not indexed in standard databases.

Inclusion criteria and exclusion criteria

Inclusion Criteria:

  1. 1.

    Study Design: Only peer-reviewed studies, including randomized controlled trials (RCTs), cohort studies, and case-control studies, were included.

  2. 2.

    Participants: Studies involving patients diagnosed with lung cancer of any stage who were undergoing treatment with ICIs were considered.

  3. 3.

    Interventions and Comparators: The intervention of interest was the administration of any ICI therapy. The comparison group consisted of lung cancer patients with concurrent COPD and those without COPD. COPD was specifically defined per the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, requiring confirmation by spirometry with a FEV1/FVC ratio of less than 0.70.

  4. 4.

    Outcomes: The primary outcome evaluated was the incidence and risk of IRP in the patient cohorts. IRP was defined based on clinical symptoms, radiologic findings, and exclusion of other causes, aligning with the CTCAE v5.0 criteria.

Exclusion Criteria:

  1. 1.

    Study Design: Abstracts, conference presentations, editorials, reviews, and case reports were excluded.

  2. 2.

    Participants: Studies that did not specifically report on lung cancer patients undergoing ICI therapy were excluded.

  3. 3.

    Insufficient Data: Studies lacking specific data on the incidence or risk of IRP or those without a clear distinction between patients with and without COPD were excluded.

  4. 4.

    Quality and Bias: Studies with significant methodological flaws or high risk of bias, as determined by standardized assessment tools, were excluded.

  5. 5.

    Duplicate Data: Studies reporting duplicate data or subsets of larger studies already included in the analysis were excluded.

Data extraction

During the meta-analysis, the process of literature screening and data extraction was conducted independently by two reviewers, with subsequent cross-verification to ensure accuracy and consistency. In instances of disagreement or discrepancy, the reviewers engaged in discussion to reach consensus, and if necessary, a third reviewer was consulted for resolution. The data extracted from each study encompassed a range of critical details: the author(s) of the study, the year of publication, study location, study design, characteristics of the study population (including number of participants and tumor staging), the number of cases of IRP, instances of COPD, and the types of immunotherapeutic agents used. For data extraction, we utilized the Covidence systematic review software, which streamlined the extraction process and facilitated the management of citations and full-text review. In situations where the published report did not contain the necessary data, the original study investigators were contacted via email to request the pertinent unpublished information. This thorough and systematic approach to data extraction was fundamental to ensure comprehensive and reliable inputs for the meta-analysis.

Quality assessment

In our meta-analysis, the quality assessment of the included studies was meticulously carried out by two independent evaluators employing the Newcastle-Ottawa Scale (NOS) [13]. This scale, recognized for its robustness, evaluates studies based on a comprehensive set of nine criteria distributed among three essential domains: selection, comparability, and outcome. These domains were instrumental in identifying potential biases within the included studies. Each study was then scored on a scale from 0 to 9, based on these criteria. The scoring was interpreted as follows: a score of 0 to 3 indicated low-quality studies, a score between 4 and 6 signified studies of moderate quality, and a score ranging from 7 to 9 was indicative of high-quality research. This thorough quality assessment process was integral to ensuring the reliability and validity of the meta-analysis findings.

Statistical analyses

In our meta-analysis, statistical analyses were conducted to rigorously evaluate the heterogeneity across the included studies. This assessment was carried out using chi-square statistics, with the degree of heterogeneity quantified by the I2 value. The choice between fixed-effect and random-effects models was determined based on the I2 statistic; a fixed-effect model was applied when the I2 value was less than 50% and the corresponding P-value was 0.10 or higher, suggesting minimal heterogeneity among the included studies. Conversely, a random-effects model was used when the I2 value was 50% or greater, or the P-value was less than 0.10, indicating significant heterogeneity, which accounts for both within-study and between-study variability. Sensitivity analysis played a critical role in our study, aiming to uncover and address potential sources of heterogeneity. This involved sequentially excluding each study and recalculating the overall effect size to evaluate the impact of individual studies on the meta-analysis. To ensure a robust approach to potential biases, especially those arising from small-study effects, both visual (funnel plot) and quantitative (Egger’s linear regression test) methods were employed. All statistical tests in our meta-analysis were two-sided, with a P-value threshold of less than 0.05 set for statistical significance. The data analyses were performed using Stata version 17 (StataCorp, College Station, TX, USA). Acknowledging the limitations inherent in using Egger’s test with fewer than ten studies, these results are considered exploratory, contributing to a cautious interpretation of potential publication bias. This comprehensive approach ensured the robustness and validity of our statistical findings.

Results

Search results and study selection

In the initial phase of our systematic review and meta-analysis, a thorough search across various electronic databases yielded a total of 1026 potentially relevant articles. An algorithm was then applied to eliminate duplicate entries, ensuring the representation of each unique study only once. Additionally, 216 records were automatically excluded by an algorithm based on exclusion keywords aimed at non-relevant content such as ‘animal studies’, ‘children’, ‘non-clinical’, or ‘mechanistic studies’, which are outside the scope of this review. This exclusion ensures that our analysis remains focused on applicable human adult cases, maintaining relevance to the clinical context of lung cancer and immunotherapy. An additional 165 records were removed due to their nature as non-research articles or their irrelevance to lung cancer, reducing the pool to 262 records eligible for the screening phase.

During the screening phase, titles and abstracts were meticulously examined, leading to the exclusion of 136 records that did not meet the inclusion criteria related to study design or population focus—specifically, those not involving lung cancer patients undergoing ICI therapy or consisting only of preliminary reports without peer-reviewed outcomes. Of the remaining 126 potentially relevant reports, 96 could not be retrieved due to issues such as broken links, access restrictions, or database unavailability, leaving 30 reports for detailed eligibility assessment.

Each of these 30 reports underwent a rigorous evaluation, including a quality assessment using the Newcastle-Ottawa Scale. This process resulted in the exclusion of 24 reports for various reasons: 9 were review articles, 6 were sequentially published articles, 3 lacked sufficient data for meaningful analysis, and 6 were clinical trials without control groups. This stringent evaluation was crucial to ensure that only high-quality, relevant studies were included. Studies scoring low (0–3 out of 9) on the scale were excluded due to significant methodological flaws or a high risk of bias.

Ultimately, only 6 studies met all the rigorous inclusion criteria outlined in our research protocol and were selected for inclusion in the final meta-analysis [14,15,16,17,18,19], as depicted in Fig. 1.

Fig. 1
figure 1

Study Selection Flowchart

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Study characteristics

The included studies in this meta-analysis encompassed a diverse range of cohorts from the United States, China, and Japan, with study periods ranging from 2004 to 2021. The studies varied in design, predominantly retrospective cohort studies, with one multicenter prospective cohort study. The total number of cases and controls across these studies varied, with the smallest study including 9 cases and the largest comprising 254 cases. The immunotherapeutic agents investigated were primarily PD-1 and PD-L1 inhibitors, with specific agents such as Pembrolizumab, Nivolumab, and Durvalumab being utilized either as monotherapy or in combination. Tumor staging across studies was reported with a majority of patients in the advanced stages of III-IV, although some studies included earlier stages or did not specify staging. The incidence of IRP reported varied significantly across studies, ranging from as low as 2.49% to as high as 25.3%. This variability highlights the heterogeneity inherent in the clinical presentations and responses to immunotherapy in lung cancer patients across different populations and treatment regimens. The studies collectively provide valuable insights into the safety profile and adverse effects associated with the use of immunotherapeutic agents in the treatment of lung cancer (Table 1).

Table 1 Basic characteristics of included studies
Full size table

Quality assessment results

The methodological quality of the included studies in this meta-analysis was evaluated using the Newcastle-Ottawa Scale, a validated tool for assessing the quality of non-randomized studies. The overall scores indicated a high level of quality among the studies, with one study achieving a score of 7, indicating good quality, and the majority of studies, totaling five, achieving scores of 8 and 9, reflecting very good to excellent quality. No instances of blinding or allocation concealment were reported across the studies, which is often the case in observational research. Furthermore, there was no indication of funding biases, suggesting that the results were not influenced by the interests of the funding sources. The integrity of the reported outcomes was robust, with no studies showing signs of incomplete outcome data, premature study termination, or significant imbalances at baseline between comparison groups. The collective risk of bias was considered low, and the specific assessments for each study were systematically tabulated (refer to Table 2 for a summarized ratio of bias risks). This comprehensive quality assessment underscores the validity and reliability of the findings presented in the meta-analysis.

Table 2 The quality assessment according to Newcastle-Ottawa Scale of each cohort study
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Meta-analysis of chronic obstructive pulmonary disease on the risk of immune-related pneumonitis in lung cancer patients treated with immunotherapeutic agents

In this meta-analysis, six studies were included to assess the impact of COPD on the risk of developing IRP among lung cancer patients receiving immunotherapy. There was a significant heterogeneity identified across the studies (I2 = 59.9%, p = 0.029). The pooled analysis revealed that lung cancer patients with concomitant COPD had an increased risk of developing IRP when undergoing immunotherapy, with an odds ratio (OR) of 1.54 [95% CI (1.24, 1.92), P < 0.01, Fig. 2]. This result suggests a substantially higher probability of IRP occurrence in patients with concurrent COPD.

Fig. 2
figure 2

Forest Plot Depicting the Impact of COPD on the Incidence of IRP Among Lung Cancer Patients Undergoing Immunotherapy

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Subgroup analysis of radiation therapy on the risk of immune-related pneumonitis in lung cancer patients treated with immunotherapeutic agents

Within the context of lung cancer, radiation therapy is known to carry a risk of radiation pneumonitis, which also represents a risk factor for the development of IRP. Considering the potential interaction between COPD and radiation therapy that might amplify the risk of IRP in lung cancer patients receiving immunotherapy, a subgroup analysis was conducted based on the proportion of patients who received radiation therapy (< 40% and ≥ 40%). The analysis revealed no significant heterogeneity within the subgroups (I2 = 43.8% for < 40% radiation therapy group and 0.0% for ≥ 40% radiation therapy group). In the cohort of patients with concomitant COPD, a significant increase in the risk of developing IRP was observed [for the < 40% radiation therapy group: OR = 1.64, 95% CI (1.30, 2.08), P < 0.01; for the ≥ 40% radiation therapy group: OR = 1.76, 95% CI (1.07, 2.89), P < 0.01, Fig. 3].

Fig. 3
figure 3

Subgroup Analysis Evaluating the Influence of Radiation Therapy on IRP Risk in Lung Cancer Patients Undergoing Immunotherapy

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Sensitivity analysis

In light of the significant heterogeneity detected across the included studies, a sensitivity analysis was undertaken to examine the robustness and consistency of the aggregate outcomes. This procedure involved the iterative removal of each study from the pool and the subsequent recalculation of the effect sizes for the residual studies. The application of this meticulous sensitivity testing procedure demonstrated that the aggregate results were not substantially altered by the omission of any individual study. This testifies to the non-disproportionate impact of any single study on the overall meta-analytic findings, thereby reinforcing the credibility and dependability of our conclusions. The constancy of the results obtained from this series of sensitivity analyses serves to solidify the validity of our principal conclusions, providing a stronger foundation for the inferences derived from our meta-analysis, as depicted in Fig. 4.

Fig. 4
figure 4

Sensitivity Analysis for Assessing the Effect of COPD on IRP Risk in Lung Cancer Patients Receiving Immunotherapeutic Agents

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Publication bias

An evaluation of potential publication bias within our meta-analysis was performed using funnel plot analysis and Egger’s linear regression test. The funnel plots, representing the studies included, demonstrated a symmetric distribution, which suggests an absence of publication bias (Fig. 5). Consistent with the visual assessment provided by the funnel plots, Egger’s linear regression test confirmed no statistically significant publication bias across the various variables analyzed (all P-values > 0.05). We underscore the use of Egger’s test as exploratory rather than confirmatory, primarily aimed at providing an additional layer of analysis that could be informative, albeit not definitive. This lack of significant publication bias substantiates the robustness and reliability of the results obtained from our meta-analysis.

Fig. 5
figure 5

Funnel Plot for Assessing Publication Bias Across the Included Studies

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Discussion

Lung cancer remains the most prevalent and deadliest malignancy worldwide, accounting for a significant proportion of cancer-related mortality. Despite advances in early detection and conventional treatments like surgery, chemotherapy, and radiation therapy, the prognosis for lung cancer patients, especially those with advanced stages, remains suboptimal [20, 21]. The advent of immunotherapy, particularly ICIs, has transformed the therapeutic landscape, offering a new avenue for durable responses and prolonged survival. However, the promising benefits of immunotherapy come with the risk of immune-related adverse events (irAEs), notably IRP [22, 23]. IRP is a potentially fatal complication that can compromise respiratory function and quality of life, necessitating the discontinuation of life-prolonging therapy. Among the risk factors for IRP, the presence of COPD has been identified as a significant contributor [24]. Patients with COPD are more prone to developing IRP due to pre-existing lung inflammation and compromised pulmonary immunity, which may interact with the immunomodulatory mechanisms of ICIs. This systematic review and meta-analysis is the first to synthesize evidence on the impact of COPD on the risk of IRP in lung cancer patients undergoing immunotherapy. It highlights the necessity for heightened surveillance and tailored management strategies for patients with concurrent COPD [25]. By identifying this specific population at higher risk, oncologists can better navigate the risks and benefits of immunotherapy, potentially leading to the development of predictive models for IRP and preventative measures to mitigate its occurrence.

The findings from the meta-analysis underscore the critical influence of COPD on the risk of IRP in lung cancer patients treated with immunotherapeutic agents. The significant heterogeneity observed might be attributable to variations in study populations, the types and stages of lung cancer, COPD severity, and different immunotherapeutic regimens. The elevated OR indicates a noteworthy clinical consideration for practitioners when managing lung cancer patients with pre-existing COPD, as these patients are at a heightened risk for IRP, a potentially severe and treatment-limiting adverse event. The increased risk could be due to the underlying inflammatory state and altered pulmonary immune environment associated with COPD, which may interact with the mechanisms of action of immune checkpoint inhibitors, leading to an exacerbated inflammatory response in the lungs.

The results of this meta-analysis indicate that lung cancer patients with COPD are at an elevated risk of developing IRP, particularly when exposed to higher levels of radiation therapy. The finding that this increased risk persists across different levels of radiation exposure (< 40% and ≥ 40%) suggests that COPD is an independent risk factor for IRP, and when combined with the risk associated with radiation therapy, may compound the likelihood of this adverse event. The absence of significant heterogeneity within these subgroups provides confidence in the consistency of the findings. The increased odds ratios in both subgroups underscore the need for careful consideration and potential modification of both immunotherapy and radiation therapy regimens in patients with pre-existing COPD. Clinicians should be cognizant of the compounded risk in these patients and may need to implement enhanced monitoring protocols or consider alternative therapeutic strategies to mitigate this risk [26]. These results highlight the importance of vigilant monitoring and potentially early intervention for signs of pneumonitis in this patient population. Further research is needed to elucidate the pathophysiological pathways linking COPD with increased IRP risk and to develop strategies to mitigate this risk, ensuring optimal treatment outcomes for lung cancer patients with COPD undergoing immunotherapy.

Recent studies have also made progress in this research direction, reflecting a growing understanding of IRP risks associated with ICIs. Zhou et al.‘s [27] study corroborates our findings by linking ICIs with an increased risk of IRP, particularly emphasizing the exacerbating influence of pre-existing lung conditions and treatment history. Unlike Zhou et al.‘s broader cancer focus, our research narrows down to lung cancer patients with COPD, providing more detailed insights into this specific subgroup. This distinction is crucial for highlighting the necessity for tailored monitoring and intervention strategies for COPD patients treated with ICIs. Furthermore, Zhao et al.‘s [28] meta-analysis underlines the heightened lung cancer prevalence among COPD patients, which complements our findings regarding the compounded risk of IRP in these patients undergoing ICI therapy. Our study expands on their conclusions by illustrating the essential need for rigorous IRP surveillance and adapted treatment approaches for lung cancer patients with pre-existing COPD. Additionally, Kong et al. [29]. explore CIP risks in advanced NSCLC, focusing on the roles of histology, PD-L1 expression, and previous treatment history. Our findings align with theirs by identifying increased IRP risks in COPD patients, enhancing our understanding of IRP risk factors. By specifically quantifying the impact of COPD—a prevalent comorbidity in lung cancer—our research contributes a significant dimension to the stratification and management of IRP risks, advocating for precision in clinical practice and patient care. This collective body of work underscores the importance of integrating these insights into clinical guidelines to optimize the safety and efficacy of ICI therapies in lung cancer management.

The significant knowledge gap regarding the role of COPD as a potential risk factor for IRP in patients treated with ICIs is a critical issue that merits thorough exploration. COPD, characterized by chronic inflammation and structural changes in the lung, may predispose patients to heightened immunological reactivity when exposed to the modulatory effects of ICIs. This interaction could theoretically amplify the risk of developing IRP, a severe and potentially life-threatening adverse event. Understanding the mechanistic interplay between pre-existing COPD and the onset of IRP is essential for developing targeted strategies to mitigate risks and enhance patient outcomes. This understanding could guide clinicians in tailoring immunotherapy treatments and monitoring strategies, particularly in a population already vulnerable due to compromised pulmonary function. Therefore, addressing this gap not only contributes to our scientific understanding but also has direct clinical implications in improving the safety and efficacy of ICI therapies in lung cancer management.

One primary limitation of this study is the inherent heterogeneity among the included studies, particularly in terms of patient demographics, tumor staging, and types of immunotherapies used, which might influence the generalizability of the results. Additionally, most included studies were observational, which inherently carry a risk of confounding factors that might affect the outcomes. Moreover, our inability to retrieve full texts for some records, initially deemed potentially relevant from their abstracts, was hindered by issues such as broken links and access restrictions. This prevented a comprehensive evaluation of these studies, potentially impacting the generalizability and applicability of our findings. The lack of randomized controlled trials in the analysis also limits the ability to establish causal relationships. Furthermore, the analysis might be constrained by the limited data on the severity and management of COPD in patients, which could have implications on the IRP risk assessment. Lastly, publication bias cannot be entirely ruled out, as studies with negative results are less likely to be published, potentially skewing the meta-analysis results.

To address the recognized gap in the literature, future studies should include larger datasets to enable more robust assessments of publication bias, which is crucial for accurately evaluating the effects of ICIs. We note the limitations of using unadjusted odds ratios in our findings, highlighting the need for future research to adopt uniformly adjusted models across studies. This will enhance comparability and ensure that results are not skewed by uncontrolled variables. Additionally, we recommend that future meta-analyses standardize adjustment factors, developing a consensus on essential variables for studying the impact of COPD on IRP in lung cancer patients treated with ICIs. Such standardization would lead to more precise effect estimations and clearer interpretability of outcomes. Regarding the inability to retrieve the full texts of some identified records, it is hoped that future research will benefit from stronger digital infrastructure and the advocacy of open access policies, which could further facilitate the inclusion of relevant studies in systematic reviews and meta-analyses, ensuring a more comprehensive coverage. Furthermore, while our focus was primarily on COPD associated with chronic bronchitis, the independent exploration of emphysema—due to its distinct inflammatory and remodeling patterns—could significantly contribute to our understanding of ICI pneumonitis. Addressing this distinction could elucidate the specific risks associated with different COPD subtypes in immune-related adverse events.

Conclusions

This study concludes that for lung cancer patients undergoing antitumor immunotherapy, the coexistence of COPD significantly elevates the risk of developing IRP. These findings underscore the need for further research and validation to refine patient management strategies and mitigate this increased risk, enhancing the safety and efficacy of immunotherapy in this vulnerable patient population.

Data availability

No datasets were generated or analysed during the current study.

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Authors and Affiliations

  1. Department of Medical Oncology, The First People’s Hospital of Linping District, No. 369, Yingbin Road, Nanyuan Street, Linping District, Hangzhou, 31110, Zhejiang Province, China

    Fangyuan Li, Lei Zheng, Xiaoxia Xu, Jianjiang Jin, Xingxing Li & Li Zhou

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  1. Fangyuan Li
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  2. Lei Zheng
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  3. Xiaoxia Xu
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  4. Jianjiang Jin
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  5. Xingxing Li
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  6. Li Zhou
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Contributions

guarantor of integrity of the entire study: Fangyuan Li; study concepts: Lei Zheng; study design: Xiaoxia Xu; definition of intellectual content: Xiaoxia Xu; literature research: Fangyuan Li; clinical studies: Jianjiang Jin; experimental studies: Lei Zheng; data acquisition: Fangyuan Li; data analysis: Lei Zheng; statistical analysis: Jianjiang Jin; manuscript preparation: Xingxing Li; manuscript editing: Fangyuan Li; manuscript review: Li Zhou.

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Li, F., Zheng, L., Xu, X. et al. The impact of chronic obstructive pulmonary disease on the risk of immune-related pneumonitis in lung cancer patients undergoing immunotherapy: a systematic review and meta-analysis. BMC Pulm Med 24, 393 (2024). https://doi.org/10.1186/s12890-024-03180-w

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  • DOI: https://doi.org/10.1186/s12890-024-03180-w

Keywords

BMC Pulmonary Medicine

ISSN: 1471-2466

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