Impact of COPD treatment on survival in patients with advanced non-small cell lung cancer

doi:10.21203/rs.3.rs-741440/v1

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Impact of COPD treatment on survival in patients with advanced non-small cell lung cancer

https://doi.org/10.21203/rs.3.rs-741440/v1

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published 23 Apr, 2022

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Background

Chronic obstructive pulmonary disease (COPD) is associated with a poor prognosis in patients with non-small cell lung cancer (NSCLC). However, the impact of COPD treatment on the survival of patients with advanced NSCLC remains uncertain.

Methods

We retrospectively investigated COPD patients among patients newly diagnosed with advanced NSCLC between September 2005 and August 2019 at a university hospital. The diagnosis of COPD was made by forced expiratory volume in 1 second (FEV₁)/forced vital capacity < 0.7 with spirometry performed within one year before and after the diagnosis of NSCLC. The clinical characteristics, lung function, and survival outcomes were analyzed and compared between patients who did and did not receive COPD treatment.

Results

Among 221 patients with advanced NSCLC and COPD, 124 received treatment for COPD and 97 did not receive treatment for COPD. A total of 190 (86.0%) patients were newly diagnosed with COPD at the time of diagnosis of advanced NSCLC. FEV₁ and FEV₁ % predicted values were greater in the no-treatment group than in the COPD treatment group (P < 0.001). The median overall survival (OS) of the treatment group was 10.7 months while that of the no-treatment group was 8.7 months (P = 0.007). In multivariate Cox regression analysis, COPD treatment was independently associated with improved OS after adjustment for sex, age, body mass index, FEV₁, lung cancer stage, and chemotherapy (hazard ratio, 0.71; 95% confidence interval, 0.53–0.95; P = 0.021).

Conclusion

COPD treatment was associated with improved OS in patients with advanced NSCLC and COPD. Therefore, pretreatment spirometry and maximal treatment for COPD may offer a chance of optimal management for patients with advanced NSCLC.

Internal Medicine

bronchodilator

chronic obstructive pulmonary disease

inhaled corticosteroids

non-small cell lung cancer

survival

Lung cancer is the leading cause of cancer-related deaths worldwide. Chronic obstructive pulmonary disease (COPD) is an important comorbidity of lung cancer, sharing a common risk factor, cigarette smoking. Around 30%-70% of lung cancer patients also have COPD [1–3]. COPD is associated with an increased risk during surgical resection, which offers the best prospect of long-term survival in patients with anatomically resectable non-small cell lung cancer (NSCLC) [4–6]. Even in the operable stage of NSCLC, patients with severe COPD generally cannot undergo surgery due to their high risk. Therefore, for patients with resectable NSCLC, spirometry is an essential test before surgery. Older smokers who have not experienced dyspnea, probably due to their habitual low activity, are often diagnosed with COPD for the first time as a result of spirometry during a pre-surgical examination for NSCLC. Several studies have reported that preoperative treatment with long-acting muscarinic antagonist (LAMA), long-acting β₂-agonist (LABA), and/or inhaled corticosteroids (ICS), reduces the incidence of postoperative complications [7–10].

Similarly, in advanced NSCLC, several studies have reported that forced expiratory volume in 1 second (FEV₁) less than 50% predicted or the presence of COPD were associated with mortality [11–13]. Because severity of airflow obstruction and acute exacerbations are predictors of mortality in COPD patients [14–16], improving these factors might also be important in patients with advanced NSCLC and COPD. Particularly, ICS is associated with decreased mortality in COPD [17–19]. Nevertheless, few studies have investigated whether COPD treatment improves the survival of patients with advanced NSCLC.

The aim of the present study was to investigate the impact of COPD treatment on survival in patients with advanced NSCLC.

Study population

We retrospectively investigated patients who were newly diagnosed with advanced NSCLC (inoperable stage IIIA to IV) between September 2005 and August 2019 at Ewha Womans University Mokdong Hospital, Seoul, Republic of Korea (Fig. 1). Among these, patients with spirometrically diagnosed COPD or patients who had already received treatment for COPD were included in the present study. The post-bronchodilator FEV₁/forced vital capacity (FVC) < 0.7 was applied to define COPD. Patients were excluded if they had undergone surgical resection, did not have a histological diagnosis, were transferred to another hospital or dropped out immediately after the diagnosis. We also excluded patients who harbored target mutations, such as epidermal growth factor receptor mutation and anaplastic lymphoma kinase rearrangement, and consequently received targeted therapies since they have a much better prognosis [20].

Data collection and assessment

Baseline clinical characteristics including age, sex, body mass index (BMI), smoking history, histological type, lung cancer stage, cancer treatment-related matters, and COPD treatment regimen were collected retrospectively using medical records. To diagnose COPD and determine the severity of airflow obstruction, spirometry performed within one year before and after the diagnosis of lung cancer was used.

The study subjects were divided into two groups according to whether they received COPD treatment or not. The COPD treatment group included patients who received inhaled therapy and/or theophylline. The no-treatment group included those who did not receive any treatment for COPD. The primary end-point of the present study was to compare overall survival (OS) among these groups. In addition, we also investigated whether there was a difference in OS according to the COPD treatment regimens. OS was defined as the time from histologic diagnosis of NSCLC to death.

Statistical analysis

The Pearson chi-square test or Fisher’s exact test was used to compare categorical variables and Student’s t-test was used to compare continuous variables. OS curves were plotted using the Kaplan-Meier method and were compared using a log-rank test. Hazard ratios (HRs) for univariate and multivariate survival analyses were calculated using the Cox proportional hazard model. All tests of significance were 2-sided, and differences among groups were considered significant when P < 0.05. All statistical analyses were performed using SPSS for Windows, version 27.0 (SPSS Inc., Chicago, IL, USA).

Baseline characteristics

A total of 221 patients with coexisting advanced NSCLC and COPD were included in the present study. Among these, 124 patients received COPD treatment and 97 did not receive COPD treatment. The baseline demographic and clinical characteristics of the patients are presented in Table 1. The mean age of the 221 patients was 70.7 ± 9.0 years old and 200 (90.5%) were men. There was a significant difference in lung cancer stage, where 61.9% of the no-treatment group had stage IV, while only 44.4% of the COPD treatment group had stage IV disease (P = 0.010). A total of 190 (86.0%) patients were newly diagnosed with COPD at the time of diagnosis of advanced NSCLC. A significantly higher proportion of patients in the no-treatment group were newly diagnosed COPD patients compared with the COPD treatment group (99.0% vs. 75.8%, P < 0.001). In addition, the no-treatment group showed better baseline FVC, FEV₁, and carbon monoxide diffusing capacity compared with the COPD treatment group (Table 2). One hundred five (84.7%) patients received inhalation therapy; triple therapy (ICS/LABA/LAMA) was the most commonly used regimen (45/124, 36.3%), followed by LAMA/LABA combination (22/124, 17.7%) and LAMA alone (20/124, 16.1%, Table 3).

Table 1

Comparison of baseline characteristics by COPD treatment status
	Total n = 221	Treatment n = 124	No treatment n = 97	P Value
Sex, men	200 (90.5)	114 (91.9)	86 (88.7)	0.410
Age, years	70.7 ± 8.97	71.2 ± 7.79	70.0 ± 10.3	0.330
BMI, kg/m²	22.3 ± 3.19	22.3 ± 3.29	22.4 ± 3.06	0.873
Smoking				0.084
Never smoker	37 (16.7)	16 (12.9)	21 (21.6)
Ever smoker	184 (83.3)	108 (87.1)	76 (78.4)
Histology				0.090
SqCC	117 (52.9)	70 (56.5)	47 (48.5)
ADC	77 (34.8)	36 (29.0)	41 (42.3)
P/D carcinoma	27 (12.2)	18 (14.5)	9 (9.3)
COPD diagnosis				< 0.001
New COPD	190 (86.0)	94 (75.8)	96 (99.0)
Known COPD	31 (14.0)	30 (24.2)	1 (1.0)
Clinical stage				0.010
III	106 (48.0)	69 (55.6)	37 (38.1)
IV	115 (52.0)	55 (44.4)	60 (61.9)
Chemotherapy				0.451
Chemotherapy	165 (74.7)	95 (76.6)	70 (72.2)
No chemotherapy	56 (25.3)	29 (23.4)	27 (27.8)
Radiotherapy				0.452
CCRT	54 (24.4)	33 (26.6)	21 (21.6)
Palliative	12 (5.4)	5 (4.0)	7 (7.2)
No radiotherapy	155 (70.1)	86 (69.4)	69 (71.1)
Follow up duration, months	9.5 (5.3–16.1)	10.7 (5.8–18.3)	8.7 (4.4–15.1)	0.013
Data are shown as n (%) per each group or means ± standard deviation or median (interquartile range)
COPD chronic obstructive pulmonary disease, BMI body mass index, SqCC squamous cell carcinoma, ADC adenocarcinoma, P/D poorly differentiated, CCRT concurrent chemoradiation therapy

Table 2

Comparison of lung function by COPD treatment status
	Total n = 221	Treatment n = 124	No treatment n = 97	P Value
FVC, liters	2.91 ± 0.81	2.81 ± 0.76	3.04 ± 0.86	0.035
FVC % predicted	77.8 ± 18.2	75.7 ± 17.9	80.5 ± 18.3	0.053
FEV_1, liters	1.68 ± 0.55	1.53 ± 0.48	1.87 ± 0.58	< 0.001
FEV₁ % predicted	65.3 ± 18.7	60.2 ± 16.8	71.8 ± 19.0	< 0.001
FEV1/FVC	57.9 ± 10.4	55.1 ± 11.2	61.5 ± 7.90	< 0.001
DLco, % predicted	68.7 ± 27.5 ^a	64.7 ± 25.8 ^b	74.0 ± 28.8 ^c	0.033
COPD severity by GOLD classification ^d				< 0.001
GOLD 1	52 (23.5)	17 (13.7)	35 (36.1)
GOLD 2	121 (54.8)	72 (58.1)	49 (50.5)
GOLD 3	44 (19.9)	33 (26.6)	11 (11.3)
GOLD 4	4 (1.8)	2 (1.6)	2 (2.1)
Data are shown as n (%) per each group or means ± standard deviation
^a Data are from 160 patients
^b Data are from 90 patients
^c Data are from 70 patients
^d P value was calculated from the Fisher’s exact test
COPD chronic obstructive pulmonary disease, FVC forced vital capacity, FEV₁ forced expiratory volume in 1 second, DLco diffusing capacity of carbon monoxide, GOLD the Global Initiative for Chronic Obstructive Lung Disease
GOLD 1, FEV₁ ≥ 80% predicted; GOLD 2, 50% ≤ FEV₁ < 80% predicted; GOLD 3, 30% ≤ FEV₁ < 50% predicted; GOLD 4, FEV₁ < 30% predicted

Table 3

Type of COPD treatment
Type of treatment	n = 124
Inhalers
LAMA	20 (16.1)
LABA	2 (1.6)
LAMA/LABA	22 (17.7)
ICS/LABA	16 (12.9)
ICS/LAMA/LABA	45 (36.3)
No use	19 (15.3)
Theophylline
Use	69 (55.6)
No use	55 (44.4)
Data are presented as number (%)
LAMA long-acting muscarinic antagonist, LABA long-acting β₂-agonist, ICS inhaled corticosteroids

Overall survival

The treatment group showed significantly improved median OS compared with the no-treatment group (10.7 months, 95% confidence interval [CI], 8.3–13.0, vs. 8.7 months, 95% CI, 7.5–9.9, P = 0.007, Fig. 2A). We also investigated whether there was a difference in OS according to treatment regimens. The Kaplan-Meier survival curves revealed that all types of COPD treatment were associated with improved median OS. Patients who received inhalation therapy showed a median OS of 10.9 months, while the other patients had a median OS of 8.9 months (P = 0.021, Fig. 2B). The use of ICS (12.2 months vs. 8.8 months, P = 0.006, Fig. 2C) and theophylline (11.4 months vs. 8.7 months, P = 0.016, Fig. 2D) also resulted in significantly improved OS versus the untreated patients. In subgroup analysis according to clinical stages, median OS was significantly different according to COPD treatment status in stage III (12.0 months vs. 10.4 months, P = 0.032, Additional file 1: Fig. S1A); however, there was no significant difference in stage IV (7.2 months vs. 6.6 months, P = 0.366, Additional file 1: Fig. S1B).

In univariate analysis, sex, BMI, FEV₁ less than 50% predicted, FVC, stage, chemotherapy, COPD treatment, inhaler use, ICS use, and theophylline-containing treatment were revealed as significant prognostic factors predicting OS (all P < 0.05). In multivariate Cox regression analysis, men (HR, 2.49; 95% CI, 1.52–4.10; P < 0.001) and stage IV disease (HR, 1.94; 95% CI, 1.44–2.62; P < 0.001) were independent predictors of a worse OS, whereas higher BMI (HR, 0.95; 95% CI, 0.91–0.99; P = 0.033), chemotherapy (HR, 0.44; 95% CI, 0.31–0.62; P < 0.001), and COPD treatment (HR, 0.71; 95% CI, 0.53–0.95; P = 0.021) were independent predictors of better OS (Table 4). When applying inhalation therapy or ICS instead of COPD treatment with the same variables, inhalation therapy (HR, 0.72; 95% CI, 0.54–0.97; P = 0.029; Additional file 2: Table S1) and ICS were independent predictors of a better OS (HR, 0.67; 95% CI, 0.49–0.92; P = 0.012; Additional file 2: Table S2). However, theophylline administration was not an independent predictor of OS (HR, 0.79; 95% CI, 0.58–1.08; P = 0.135; Additional file 2: Table S3).

Table 4

Clinical factor associated with overall survival (univariate analysis)
Variables	Univariate			Multivariate
Variables	HR	95% CI	P Value	HR	95% CI	P Value
Sex, men	1.62	1.02–2.56	0.042	2.49	1.52–4.10	< 0.001
Age, years	1.00	0.98–1.02	0.846	0.99	0.98–1.01	0.313
BMI, kg/m²	0.95	0.91–0.99	0.038	0.95	0.91–0.99	0.033
Ever smoker	1.02	0.72–1.46	0.896
FEV₁ < 50% predicted	1.40	1.01–1.95	0.044	1.26	0.90–1.79	0.184
Histology
ADC	1.00
SqCC	1.05	0.79–1.41	0.736
P/D carcinoma	1.17	0.75–1.81	0.497
Clinical stage
III	1.00			1.00
IV	1.62	1.24–2.13	< 0.001	1.94	1.44–2.62	< 0.001
Chemotherapy	0.59	0.44–0.81	0.001	0.44	0.31–0.62	< 0.001
CCRT	0.98	0.66–1.24	0.542
COPD treatment	0.69	0.52–0.91	0.007	0.71	0.53–0.95	0.021
Inhaled therapy	0.73	0.55–0.95	0.021
ICS	0.65	0.48–0.89	0.006
Theophylline	0.70	0.52–0.94	0.017
HR hazard ratio, CI confidence interval, BMI body mass index, FEV₁ forced expiratory volume in 1 second, ADC adenocarcinoma, SqCC squamous cell carcinoma, P/D poorly differentiated, CCRT concurrent chemoradiation therapy, COPD chronic obstructive pulmonary disease, ICS inhaled corticosteroids

This is the first study to investigate the impact of COPD treatment on the survival of patients with advanced NSCLC. The current study demonstrated that COPD treatment was associated with improved OS in patients with advanced NSCLC even though the COPD treatment group had worse baseline lung function than the no-treatment group. When OS was analyzed for each type of COPD treatment, inhalation therapy and the use of ICS were associated with improvements in OS.

COPD is an important comorbidity for lung cancer patients. Therefore, several studies have investigated the relationship between COPD and the prognosis of lung cancer patients. In patients with inoperable NSCLC, FEV₁ < 60% predicted or diffusing lung capacity < 60% predicted were both associated with a worse prognosis [11, 21]. FEV₁ itself is a predictor of mortality, not only in COPD patients but also in the general population [14, 22]. For patients with operable lung cancer, preoperative spirometry is essential, whereas spirometry may not be necessary for patients with inoperable lung cancer, particularly if they do not complain of respiratory symptoms, in which case clinicians are likely to focus only on lung cancer. Since physical activity usually decreases with age, patients with mild to moderate COPD, usually defined as FEV₁ ≥ 50% predicted, do not experience or overlook their respiratory symptoms in many cases. In this study, 86% of patients with advanced NSCLC were diagnosed with COPD for the first time. Unfortunately, out of 190 patients with newly diagnosed COPD, only 94 (49%) were treated for their COPD. These results indicate that the identification of COPD through spirometry and active treatment for COPD are essential before treatment of their cancer.

In COPD patients, inhaled therapy, including LAMA, LABA, ICS, and combination therapy, have shown improvements in lung function, quality of life, and exacerbations [18, 23–25]. However, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) noted a lack of convincing evidence for a survival benefit with inhaled therapy in COPD. Recent large randomized trials showed a survival benefit of ICS-containing combination therapy over dual bronchodilator therapy with LAMA-LABA [18, 19]. Interestingly, according to a nationwide study of COPD patients in Korea, ICS users appear to have a lower risk of lung cancer compared with nonusers [26]. It is hypothesized that ICS, which reduces the risk of acute exacerbations through anti-inflammatory action in COPD patients, reduces the risk of lung cancer, a type of chronic inflammation. In this study, ICS was shown to prolong the survival of patients with advanced NSCLC. It is possible that the anti-inflammatory action of ICS inhibits cancer progression. There is also a report that ICS lowered the risk of coronary heart disease in COPD patients [27]. Therefore, the use of ICS may have had an effect on cardiovascular mortality in our study subjects. Since detailed information on the cause of death was not available for many of our subjects, it was not possible to evaluate whether inhaled therapy was associated with cancer progression or other fatal complications, such as exacerbation of COPD, pneumonia, and cardiovascular events. Inhaled therapy may have also influenced their performance status, which is a major factor in determining whether to treat lung cancer, and is itself an important prognostic factor in lung cancer patients [28].

In COPD patients, ICS increases the risk of pneumonia [29–31]. Pneumonia is one of the most life-threatening complications of lung cancer patients. However, previous studies have demonstrated consistent results that the use of ICS does not increase pneumonia-related mortality in COPD patients, and instead it is associated with decreased mortality in hospitalized pneumonia patients [17, 32]. This might suggest a double effect of ICS, an immunosuppressive effect and an anti-inflammatory effect. ICS, which achieves locally high concentrations in the lung, up-regulates the production of anti-inflammatory proteins and inhibits the transcription of proinflammatory cytokines and chemokines [33]. In a previous study of patients receiving cisplatin-containing chemotherapy, inhaled fluticasone reduced the incidence of delayed pulmonary toxicity [34]. Because there are also reports that different kinds of ICS have different impacts on the incidence of pneumonia, we need to make careful choices about ICS type and dose [30, 35].

The present study has several limitations. First, it was a single-center study and not all patients with newly diagnosed advanced NSCLC had performed spirometry, so there may have been selection bias. Second, it was not possible to investigate their performance status. Performance status is an important prognostic factor and may affect treatment decision-making [36–38]. Nevertheless, BMI and undergoing cytotoxic chemotherapy might indirectly reflect their performance status, and these factors were adjusted for the analysis. Third, it is not clear why the no treatment group did not receive COPD treatment. As this study was a retrospective study, the respiratory symptoms of the study subjects were not evaluated. Nevertheless, the fact that the no treatment group had better lung function than the COPD treatment group strongly suggests the possibility of not receiving COPD treatment due to no respiratory symptoms. Even if a doctor tried to prescribe an inhalation drug, it is likely that a patient with no symptoms refused it. Fourth, although COPD is characterized by not fully reversible airflow obstruction, we were unable to evaluate whether lung function or dyspnea improved after treatment in the COPD treatment group.

COPD treatment is associated with improved survival in patients with both advanced NSCLC and COPD. Also, this study showed that ICS and inhalation therapy are associated with improved OS. In patients with advanced NSCLC, finding COPD through spirometry before cancer treatment and treating the COPD as well as the lung cancer could improve survival.

BMI = body mass index; CI = confidence interval; COPD = chronic obstructive pulmonary disease; FEV₁ = forced expiratory volume in 1 second; FVC = forced vital capacity; HR = hazard ratio; ICS = inhaled corticosteroids; LABA = long-acting β₂-agonist; LAMA = long-acting muscarinic antagonist; NSCLC = non-small cell lung cancer; OS = overall survival

Author contributions

H. J. had full access to all the data in the study and takes responsibility for the integrity of the data and accuracy of the analysis. J. H. L. and H. J. conceived and designed the study. All authors acquired the clinical data. H. J. conducted the statistical analysis. All authors analyzed and interpreted the data. H. J., S. P., and J. H. L. drafted the manuscript. All authors critically revised the manuscript for important intellectual content and approved the submitted version.

Acknowledgements

This work was supported by the National Research Foundation of Korea (NRF-2020R1A5A2019210). We thank Hye Ah Lee (Clinical Trial Center, Ewha Womans University Mokdong Hospital) for her contribution to the statistical analysis and Eun Hwa Kang (Informatization department, Ewha Womans University Seoul Hospital) for her contribution to assessment of the patients’ clinical data.

Funding

This analysis did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Competing interests

The authors declare no conflict of interest.

Availability of data and materials

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

Ethics approval and consent to participate

The study protocol was approved by the Institutional Review Board of Ewha Womans University Hospital (IRB No. 2020-05-012), which waived the requirement for informed consent because of the retrospective nature of the analysis. This study was conducted in accordance with the Declaration of Helsinki.

Consent for publication

Not applicable

Loganathan RS, Stover DE, Shi W, Venkatraman E. Prevalence of COPD in women compared to men around the time of diagnosis of primary lung cancer. Chest. 2006;129(5):1305–12.
Young RP, Hopkins RJ, Christmas T, Black PN, Metcalf P, Gamble GD. COPD prevalence is increased in lung cancer, independent of age, sex and smoking history. Eur Respir J. 2009;34(2):380–6.
Parron Collar D, Pazos Guerra M, Rodriguez P, Gotera C, Mahillo-Fernandez I, Peces-Barba G, et al. COPD is commonly underdiagnosed in patients with lung cancer: results from the RECOIL study (retrospective study of COPD infradiagnosis in lung cancer). Int J Chron Obstruct Pulmon Dis. 2017;12:1033–8.
Win T, Jackson A, Sharples L, Groves AM, Wells FC, Ritchie AJ, et al. Relationship between pulmonary function and lung cancer surgical outcome. Eur Respir J. 2005;25(4):594–9.
Greillier L, Thomas P, Loundou A, Doddoli C, Badier M, Auquier P, et al. Pulmonary function tests as a predictor of quantitative and qualitative outcomes after thoracic surgery for lung cancer. Clin Lung Cancer. 2007;8(9):554–61.
Zhai R, Yu X, Shafer A, Wain JC, Christiani DC. The impact of coexisting COPD on survival of patients with early-stage non-small cell lung cancer undergoing surgical resection. Chest. 2014;145(2):346–53.
Kobayashi S, Suzuki S, Niikawa H, Sugawara T, Yanai M. Preoperative use of inhaled tiotropium in lung cancer patients with untreated COPD. Respirology. 2009;14(5):675–9.
Nojiri T, Inoue M, Yamamoto K, Maeda H, Takeuchi Y, Nakagiri T, et al. Inhaled tiotropium to prevent postoperative cardiopulmonary complications in patients with newly diagnosed chronic obstructive pulmonary disease requiring lung cancer surgery. Surg Today. 2014;44(2):285–90.
Makino T, Otsuka H, Hata Y, Koezuka S, Azuma Y, Isobe K, et al. Long-acting muscarinic antagonist and long-acting beta2-agonist therapy to optimize chronic obstructive pulmonary disease prior to lung cancer surgery. Mol Clin Oncol. 2018;8(5):647–52.
Bolukbas S, Eberlein M, Eckhoff J, Schirren J. Short-term effects of inhalative tiotropium/formoterol/budenoside versus tiotropium/formoterol in patients with newly diagnosed chronic obstructive pulmonary disease requiring surgery for lung cancer: a prospective randomized trial. Eur J Cardiothorac Surg. 2011;39(6):995–1000.
Lee JH, Song EM, Sim YS, Ryu YJ, Chang JH. Forced expiratory volume in one second as a prognostic factor in advanced non-small cell lung cancer. J Thorac Oncol. 2011;6(2):305–9.
Lee SY, Choi YJ, Seo JH, Lee SY, Kim JS, Kang EJ. Pulmonary function is implicated in the prognosis of metastatic non-small cell lung cancer but not in extended disease small cell lung cancer. J Thorac Dis. 2019;11(11):4562–72.
Lim JU, Yeo CD, Rhee CK, Kang HS, Park CK, Kim JS, et al. Comparison of clinical characteristics and overall survival between spirometrically diagnosed chronic obstructive pulmonary disease (COPD) and non-COPD never-smoking stage I-IV non-small cell lung cancer patients. Int J Chron Obstruct Pulmon Dis. 2019;14:929–38.
Celli BR, Cote CG, Marin JM, Casanova C, Montes de Oca M, Mendez RA, et al. The body-mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic obstructive pulmonary disease. N Engl J Med. 2004;350(10):1005–12.
Patil SP, Krishnan JA, Lechtzin N, Diette GB. In-hospital mortality following acute exacerbations of chronic obstructive pulmonary disease. Arch Intern Med. 2003;163(10):1180–6.
Price LC, Lowe D, Hosker HS, Anstey K, Pearson MG, Roberts CM, et al UK National COPD Audit 2003. Impact of hospital resources and organisation of care on patient outcome following admission for acute COPD exacerbation. Thorax. 2006;61(10):837–42.
Chen D, Restrepo MI, Fine MJ, Pugh MJ, Anzueto A, Metersky ML, et al. Observational study of inhaled corticosteroids on outcomes for COPD patients with pneumonia. Am J Respir Crit Care Med. 2011;184(3):312–6.
Lipson DA, Barnhart F, Brealey N, Brooks J, Criner GJ, Day NC, et al. Once-Daily Single-Inhaler Triple versus Dual Therapy in Patients with COPD. N Engl J Med. 2018;378(18):1671–80.
Rabe KF, Martinez FJ, Ferguson GT, Wang C, Singh D, Wedzicha JA, et al. Triple Inhaled Therapy at Two Glucocorticoid Doses in Moderate-to-Very-Severe COPD. N Engl J Med. 2020;383(1):35–48.
Lee JG, Kim HC, Choi CM. Recent Trends of Lung Cancer in Korea. Tuberc Respir Dis (Seoul). 2021;84(2):89–95.
Semrau S, Klautke G, Virchow JC, Kundt G, Fietkau R. Impact of comorbidity and age on the outcome of patients with inoperable NSCLC treated with concurrent chemoradiotherapy. Respir Med. 2008;102(2):210–8.
Duong M, Islam S, Rangarajan S, Leong D, Kurmi O, Teo K, et al. Mortality and cardiovascular and respiratory morbidity in individuals with impaired FEV1 (PURE): an international, community-based cohort study. Lancet Glob Health. 2019;7(5):e613-e23.
Tashkin DP, Celli B, Senn S, Burkhart D, Kesten S, Menjoge S, et al. A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med. 2008;359(15):1543–54.
Singh D, Papi A, Corradi M, Pavlisova I, Montagna I, Francisco C, et al. Single inhaler triple therapy versus inhaled corticosteroid plus long-acting beta2-agonist therapy for chronic obstructive pulmonary disease (TRILOGY): a double-blind, parallel group, randomised controlled trial. Lancet. 2016;388(10048):963–73.
Papi A, Vestbo J, Fabbri L, Corradi M, Prunier H, Cohuet G, et al. Extrafine inhaled triple therapy versus dual bronchodilator therapy in chronic obstructive pulmonary disease (TRIBUTE): a double-blind, parallel group, randomised controlled trial. Lancet. 2018;391(10125):1076–84.
Lee YM, Kim SJ, Lee JH, Ha E. Inhaled corticosteroids in COPD and the risk of lung cancer. Int J Cancer. 2018;143(9):2311–8.
Shin J, Yoon HY, Lee YM, Ha E, Lee JH. Inhaled corticosteroids in COPD and the risk for coronary heart disease: a nationwide cohort study. Sci Rep. 2020;10(1):18973.
Simmons CP, Koinis F, Fallon MT, Fearon KC, Bowden J, Solheim TS, et al. Prognosis in advanced lung cancer–A prospective study examining key clinicopathological factors. Lung Cancer. 2015;88(3):304–9.
Crim C, Dransfield MT, Bourbeau J, Jones PW, Hanania NA, Mahler DA, et al. Pneumonia risk with inhaled fluticasone furoate and vilanterol compared with vilanterol alone in patients with COPD. Ann Am Thorac Soc. 2015;12(1):27–34.
Yang M, Du Y, Chen H, Jiang D, Xu Z. Inhaled corticosteroids and risk of pneumonia in patients with chronic obstructive pulmonary disease: A meta-analysis of randomized controlled trials. Int Immunopharmacol. 2019;77:105950.
Lee JH, Park YH, Kang DR, Lee SJ, Lee MK, Kim SH, et al. Risk of Pneumonia Associated with Inhaled Corticosteroid in Patients with Chronic Obstructive Pulmonary Disease: A Korean Population-Based Study. Int J Chron Obstruct Pulmon Dis. 2020;15:3397–406.
Malo de Molina R, Mortensen EM, Restrepo MI, Copeland LA, Pugh MJ, Anzueto A. Inhaled corticosteroid use is associated with lower mortality for subjects with COPD and hospitalised with pneumonia. Eur Respir J. 2010;36(4):751–7.
Barnes PJ. Corticosteroid effects on cell signalling. Eur Respir J. 2006;27(2):413–26.
McGaughey DS, Nikcevich DA, Long GD, Vredenburgh JJ, Rizzieri D, Smith CA, et al. Inhaled steroids as prophylaxis for delayed pulmonary toxicity syndrome in breast cancer patients undergoing high-dose chemotherapy and autologous stem cell transplantation. Biol Blood Marrow Transplant. 2001;7(5):274–8.
Zhang Q, Li S, Zhou W, Yang X, Li J, Cao J. Risk of Pneumonia with Different Inhaled Corticosteroids in COPD Patients: A Meta-Analysis. COPD. 2020;17(4):462–9.
Albain KS, Crowley JJ, LeBlanc M, Livingston RB. Survival determinants in extensive-stage non-small-cell lung cancer: the Southwest Oncology Group experience. J Clin Oncol. 1991;9(9):1618–26.
Di Maio M, Lama N, Morabito A, Smit EF, Georgoulias V, Takeda K, et al. Clinical assessment of patients with advanced non-small-cell lung cancer eligible for second-line chemotherapy: a prognostic score from individual data of nine randomised trials. Eur J Cancer. 2010;46(4):735–43.
Zukin M, Barrios CH, Pereira JR, Ribeiro Rde A, Beato CA, do Nascimento YN, et al. Randomized phase III trial of single-agent pemetrexed versus carboplatin and pemetrexed in patients with advanced non-small-cell lung cancer and Eastern Cooperative Oncology Group performance status of 2. J Clin Oncol. 2013;31(23):2849–53.

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published 23 Apr, 2022

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Impact of COPD treatment on survival in patients with advanced non-small cell lung cancer

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Abstract

Background

Methods

Results

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Background

Methods

Study population

Data collection and assessment

Statistical analysis

Results

Baseline characteristics

Overall survival

Discussion

Conclusion

Abbreviations

Declarations

References

Supplementary Files

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