Purpose

Dyspnea is highly prevalent in lung cancer survivors following curative-intent therapy. We aimed to identify clinical predictors or determinants of dyspnea and characterize its relationship with functional exercise capacity (EC).

Methods

In an analysis of data from a cross-sectional study of lung cancer survivors at the VA San Diego Healthcare System who completed curative-intent therapy for stage I-IIIA disease ≥1 mo previously, we tested a thorough list of comorbidities, lung function, and lung cancer characteristics. We assessed dyspnea using the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer Module 13 (LC13) and functional EC using the 6-minute walk. We replicated results with the University of California San Diego Shortness of Breath Questionnaire.

Results

In 75 participants at a median of 12 mo since treatment completion, the mean ± SD LC13-Dyspnea score was 35.3 ± 26.2; 60% had abnormally high dyspnea. In multivariable linear regression analyses, significant clinical predictors or determinants of dyspnea were (β [95% CI]) psychiatric illness (-20.8 [-32.4 to -9.09]), heart failure with reduced ejection fraction (-15.5 [-28.0 to -2.97]), and forced expiratory volume in the first second of expiration (-0.28 [-0.49 to -0.06]). Dyspnea was an independent predictor of functional EC (-1.54 [-2.43 to -0.64]). These results were similar with the University of California San Diego Shortness of Breath Questionnaire.

Conclusion

We identified clinical predictors or determinants of dyspnea that have pathophysiological bases. Dyspnea was independently associated with functional EC. These results have implications in efforts to reduce dyspnea and improve exercise behavior and functional EC in lung cancer survivors following curative-intent therapy.

The harm associated with lung cancer treatment include perioperative morbidity and mortality and therapy-induced toxicities in various organs, including the heart and lungs. Optimal treatment therefore entails a need for risk assessment to weigh the probabilities of benefits versus harm. Exercise testing offers an opportunity to evaluate a patient's physical fitness/exercise capacity objectively. In lung cancer, it is most often used to risk-stratify patients undergoing evaluation for lung cancer resection. In recent years, its use outside this context has been described, including in nonsurgical candidates and lung cancer survivors. In this article we review the physiology of exercise testing and lung cancer. Then, we assess the utility of exercise testing in patients with lung cancer in four contexts (preoperative evaluation for lung cancer resection, after lung cancer resection, lung cancer prognosis, and assessment of efficiency of exercise training programs) after systematically identifying original studies involving the most common forms of exercise tests in this patient population: laboratory cardiopulmonary exercise testing and simple field testing with the 6-minute walk test, shuttle walk test, and/or stair-climbing test. Lastly, we propose a conceptual framework for risk assessment of patients with lung cancer who are being considered for therapy and identify areas for further studies in this patient population.

Purpose

Lung cancer treatment can lead to negative health consequences. We analyzed the effects of curative-intent lung cancer treatment on functional exercise capacity (EC) and patient-reported outcomes (PROs).

Methods

We performed a prospective, observational cohort study of consecutive patients with stage I-IIIA lung cancer undergoing curative-intent therapy and assessed functional EC (primary outcome, six-minute walk distance (6MWD)), cancer-specific quality of life (QoL) (secondary outcome, European Organization for Research and Treatment of Cancer QoL Questionnaire Core 30 (EORTC-QLQ-C30) summary score), and exploratory outcomes including dyspnea (University of California San Diego Shortness of Breath Questionnaire (UCSD SOBQ)) and fatigue Brief Fatigue Inventory (BFI)) symptoms before and at 1 to 3 months post-treatment. We analyzed the time effect of treatment on outcomes using multivariable generalized estimating equations.

Results

In 35 enrolled participants, treatment was associated with a clinically meaningful and borderline-significant decline in functional EC ((mean change, 95% CI) 6MWD = - 25.4 m (- 55.3, + 4.47), p = 0.10), clinically meaningful and statistically significant higher dyspnea (UCSD SOBQ = + 13.1 (+ 5.7, + 20.6), p = 0.001) and fatigue (BFI = + 10.0 (+ 2.9, + 17.0), p = 0.006), but no clinically meaningful or statistically significant change in cancer-specific QoL (EORTC-QLQ-C30 summary score = - 3.4 (- 9.8, + 3.0), p = 0.30).

Conclusions

Among the first prospective analysis of the effect of curative-intent lung cancer treatment on functional EC and PROs, we observed worsening dyspnea and fatigue, and possibly a decline in functional EC but not cancer-specific QoL at 1 to 3 months post-treatment. Interventions to reduce treatment-related morbidities and improve lung cancer survivorship may need to focus on reducing dyspnea, fatigue, and/or improving functional EC.

Objective

The cost-effectiveness of exercise interventions in lung cancer survivors is unknown. We performed a model-based cost-effectiveness analysis of an exercise intervention in lung cancer survivors.

Design

We used Markov modeling to simulate the impact of the Lifestyle Interventions and Independence for Elders exercise intervention compared with usual care for stage I-IIIA lung cancer survivors after curative-intent treatment. We calculated and considered incremental cost-effectiveness ratios of less than US $100,000/quality-adjusted life-year as cost-effective and assessed model uncertainty using sensitivity analyses.

Results

The base-case model showed that the Lifestyle Interventions and Independence for Elders exercise program would increase overall cost by US $4740 and effectiveness by 0.06 quality-adjusted life-years compared with usual care and have an incremental cost-effectiveness ratio of US $79,504/quality-adjusted life-year. The model was most sensitive to the cost of the exercise program, probability of increasing exercise, and utility benefit related to exercise. At a willingness-to-pay threshold of US $100,000/quality-adjusted life-year, Lifestyle Interventions and Independence for Elders had a 71% probability of being cost-effective compared with 27% for usual care. When we included opportunity costs, Lifestyle Interventions and Independence for Elders had an incremental cost-effectiveness ratio of US $179,774/quality-adjusted life-year, exceeding the cost-effectiveness threshold.

Conclusions

A simulation of the Lifestyle Interventions and Independence for Elders exercise intervention in lung cancer survivors demonstrates cost-effectiveness from an organization but not societal perspective. A similar exercise program for lung cancer survivors may be cost-effective.

Lung cancer survivors are at risk for physical fitness and autonomic function impairments. In a cross-sectional study of consecutive lung cancer survivors post-curative intent therapy, we assessed and identified predictors of resting heart rate variability (HRV) and heart rate recovery (HRR), defined as standard deviation of normal-to-normal-R-to-R intervals (SDNN) and root-mean-square-of-successive-differences (rMSSD) from routine outpatient single 10-s electrocardiographs (ECGs) and difference in heart rate (HR) at 1-minute following and the end of the six-minute-walk-test (6MWT), respectively. In 69 participants, the mean (SD) HRR was -10.6 (6.7) beats. Significant independent predictors of HRR were age and HR change associated with the 6MWT. In a subset of 41 participants with available ECGs, the mean (SD) SDNN and rMSSD were 19.1 (15.6) and rMSSD 18.2 (14.6) ms, respectively. Significant independent predictors of HRV were supine HR, HRR, and total lung capacity. HRV/HRR may be useful physiological measures in studies aimed at improving physical fitness and/or autonomic function in lung cancer survivors.

Purpose

Lung cancer survivors are at risk for health impairments resulting from the effects and/or treatment of lung cancer and comorbidities. Practical exercise capacity (EC) assessments can help identify impairments that would otherwise remain undetected. In this study, we characterized and analyzed the association between functional EC and cancer-specific quality of life (QoL) in lung cancer survivors who previously completed curative intent treatment.

Methods

In a cross-sectional study of 62 lung cancer survivors who completed treatment ≥ 1 month previously, we assessed functional EC with the 6-min walk distance (6MWD) and cancer-specific QoL with the European Organization for Research and Treatment of Cancer QoL Questionnaire Core 30 (EORTC-QLQ-C30). Cancer-specific QoL was defined using a validated composite EORTC-QLQ-C30 summary score. Univariable (UVA) and multivariable linear regression analyses (MVA) were performed to assess the relationship between functional EC and cancer-specific QoL.

Results

Lung cancer survivors had reduced functional EC (mean 6MWD = 335 m, 65% predicted) and QoL (mean EORTC-QLQ-C30 summary score = 77, scale range 0-100). In UVA, 6MWD was significantly associated with cancer-specific QoL (R² = 0.16, p = 0.001). In MVA, in a final model that also included heart failure, obstructive sleep apnea, and psychiatric illness, 6MWD was independently associated with cancer-specific QoL (partial R² = 0.20, p = 0.001).

Conclusions

Functional EC was independently associated with cancer-specific QoL in lung cancer patients postcurative intent treatment. Exercise-based interventions aimed at improving EC may improve cancer-specific QoL in these patients.

Background

The Institute of Medicine emphasizes care timeliness as an important quality metric. We assessed treatment timeliness in stage I-IIIA lung cancer patients deemed eligible for curative intent therapy and analyzed the relationship between time to treatment (TTT) and timely treatment (TT) with survival.

Methods

We retrospectively reviewed consecutive cases of stage I-IIIA lung cancer deemed eligible for curative intent therapy at the VA San Diego Healthcare System between 10/2010-4/2017. We defined TTT as days from chest tumor board to treatment initiation and TT using guideline recommendations. We used multivariable (MVA) Cox proportional hazards regressions for survival analyses.

Results

In 177 veterans, the median TTT was 35 days (29 days for chemoradiation, 36 for surgical resection, 42 for definitive radiation). TT occurred in 33% or 77% of patients when the most or least timely guideline recommendation was used, respectively. Patient characteristics associated with longer TTT included other cancer history, high simplified comorbidity score, stage I disease, and definitive radiation treatment. In MVA, TTT and TT [HR 0.53 (95% CI 0.27, 1.01) for least timely definition] were not associated with OS in stage I-IIIA patients, or disease-free survival in subgroup analyses of 122 stage I patients [HR 1.49 (0.62, 3.59) for least timely definition].

Conclusion

Treatment was timely in 33-77% of veterans with lung cancer deemed eligible for curative intent therapy. TTT and TT were not associated with survival. The time interval between diagnosis and treatment may offer an opportunity to deliver or improve other cancer care.

Rationale

When obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) coexist in the so-called "overlap" syndrome, a high risk for mortality and morbidity has been reported. There is controversy about the prevalence of OSA in people affected by COPD.

Objectives

The purpose of this study was to investigate objective meaures of sleep-disordered breathing in patients with moderate to severe COPD to test the hypothesis that COPD is associated with an increased prevalence of OSA.

Methods

Fifty-four patients (54% men) with moderate to severe COPD were enrolled prospectively (mean ± SD, FEV1 = 42.8 ± 19.8% predicted, and FEV1/FVC = 42.3 ± 13.1). Twenty patients (37%) were on supplemental oxygen at baseline. Exercise tolerance; questionnaires related to symptoms, sleep, and quality of life; and home polysomnography were obtained.

Measurements and main results

Forty-four patients had full polysomnography suitable for analysis. OSA (apnea-hypopnea index > 5/h) was present in 29 subjects (65.9%). Sleep efficiency was poor in 45% of subjects.

Conclusions

OSA is highly prevalent in patients with moderate to severe COPD referred to pulmonary rehabilitation. Sleep quality is also poor among this selected group. These patients have greater-than-expected sleep-disordered breathing, which could be an important contributory factor to morbidity and mortality. Pulmonary rehabilitation programs should consider including a sleep assessment in patients with moderate to severe COPD and interventions when indicated to help reduce the impact of OSA in COPD.

The combination of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) is associated with substantial morbidity and mortality. We hypothesized that predictors of OSA among patients with COPD may be distinct from OSA in the general population. Therefore, we investigated associations between traditional OSA risk factors (e.g. age), and sleep questionnaires [e.g. Epworth Sleepiness Scale] in 44 patients with advanced COPD. As a second aim we proposed a pilot, simplified screening test for OSA in patients with COPD. In a prospective, observational study of patients enrolled in the UCSD Pulmonary Rehabilitation Program we collected baseline characteristics, cardiovascular events (e.g. atrial fibrillation), and sleep questionnaires [e.g. Pittsburgh Sleep Quality Index (PSQI)]. For the pilot questionnaire, a BMI ≥25 kg/m2 and the presence of cardiovascular disease were used to construct the pilot screening test. Male: 59%; OSA 66%. FEV1 (mean ± SD) = 41.0±18.2% pred., FEV1/FVC = 41.5±12.7%]. Male gender, older age, and large neck circumference were not associated with OSA. Also, Epworth Sleepiness Scale and the STOP-Bang questionnaire were not associated with OSA in univariate logistic regression. In contrast, BMI ≥25 kg/m2 (OR = 3.94, p = 0.04) and diagnosis of cardiovascular disease (OR = 5.06, p = 0.03) were significantly associated with OSA [area under curve (AUC) = 0.74]. The pilot COPD-OSA test (OR = 5.28, p = 0.05) and STOP-Bang questionnaire (OR = 5.13, p = 0.03) were both associated with OSA in Receiver Operating Characteristics (ROC) analysis. The COPD-OSA test had the best AUC (0.74), sensitivity (92%), and specificity (83%). A ten-fold cross-validation validated our results. We found that traditional OSA predictors (e.g. gender, Epworth score) did not perform well in patients with more advanced COPD. Our pilot test may be an easy to implement instrument to screen for OSA. However, a larger validation study is necessary before further clinical implementation is warranted.

Rationale

Obesity-related asthma is associated with higher disease burden than normal-weight asthma among Hispanics. Adiposity, metabolic dysregulation, and inflammation are all implicated in pathogenesis of obesity-related asthma, but their independent contributions are poorly understood.

Objective

To examine the independent contributions of body fat distribution, metabolic abnormalities and inflammation on asthma symptoms and pulmonary function among Hispanics.

Methods

Participants of the Hispanic Community Health Study/Study of Latinos with doctor-diagnosed asthma who completed an asthma symptom questionnaire and performed a valid spirometry were included in the analysis (n = 1126). Multivariate analysis was used to examine the independent association of general adiposity (assessed using body mass index), truncal adiposity (assessed by waist circumference), metabolic dysregulation (presence of insulin resistance and low HDL) and inflammation (high-sensitivity C-Reactive Protein≥3 mg/L) with reported asthma symptoms or pulmonary function measures (FEV₁, and FVC) while adjusting for demographic and clinical covariates.

Results

Of the 1126 participants, 334 (29.5%) were overweight, and 648 (57.8%) were obese. FEV₁ and FVC were lower in obese compared to normal-weight asthmatics. In analyses controlling for metabolic and adiposity factors, high hs-CRP (>7 mg/L) was associated with more symptoms (prevalence-ratio 1.27 (95%CI 1.05, 1.54), and lower FVC (β -138 ml (95%CI -27 ml, -249 ml)) and FEV₁ (β -155 ml (95% CI -38 ml, -272 ml). Low HDL was also associated with lower FVC (β -111 ml (-22 ml, -201 ml) and FEV₁ (β -100 ml (-12 ml, -188 ml)). Results were similar in men and women.

Conclusions

Our findings suggest that hs-CRP and low HDL, rather than general and truncal adiposity, are associated with asthma burden among overweight and obese Hispanic adults.