Lung function impairment in the German Lung Cancer Screening Intervention Study (LUSI): prevalence, symptoms, and associations with lung cancer risk, tumor histology and all-cause mortality

Abstract

Background: Lung cancer screening may provide a favorable opportunity for a spirometry examination, to diagnose participants with undiagnosed lung function impairments, or to improve targeting of computed tomography (CT) screening intensity in view of expected net benefit.Methods: Spirometry was performed in the CT screening arm (n=2,029) of the German Lung Cancer Screening Intervention Study (LUSI)-a trial examining the effects of annual CT screening on lung cancer mortality, in 50-69-year-old long-term smokers. Participants were classified as having chronic obstructive pulmonary disease (COPD; FEV 1 /FVC <0.7), preserved ratio impaired spirometry (PRISm; FEV 1 /FVC ≥0.7and FEV 1 % predicted <80%), or normal spirometry. Descriptive statistics were used to examine associations of COPD or PRISm with respiratory symptoms, and self-reported medical diagnoses of respiratory and other morbidities. Logistic regression and proportional hazards regression were used to examine associations of COPD and PRISm, as well as their self-reported medical diagnoses, with risks of lung cancer and all-cause mortality.Results: A total of 1,987 screening arm participants (98%) provided interpretable spirometry measurements; of these, 34.3% had spirometric patterns consistent with either COPD (18.6%) or PRISm (15.7%). Two thirds of participants with COPD or PRISm were asymptomatic, and only 23% reported a previous medical diagnosis concordant with COPD. Participants reporting a diagnosis tended to be more often current and heavier smokers, and more often had respiratory symptoms, cardiovascular comorbidities, or more severe lung function impairments. Independently of smoking history, moderate-to-severe (GOLD 2-4) COPD (OR =2.14; 95% CI: 1.54-2.98), and PRISm (OR =2.68; 95% CI: 1.61-4.40), were associated with increased lung cancer risk. Lung cancer patients with PRISm less frequently had adenocarcinomas, and more often squamous cell or small cell tumors, compared to those with normal spirometry (n=45), and both PRISm and COPD were associated with more advanced lung cancer tumor stage for screen-detected cancers.PRISm and COPD, depending on GOLD stage, were also associated with about 2-to 4-fold increases in risk of overall mortality, which to 87 percent had causes other than lung cancer.Conclusions: About one third of smokers eligible for lung cancer screening in Germany have COPD or PRISm. As these conditions were associated with detection of lung cancer, spirometry may help identify populations at high risk for death of lung cancer or other causes, and who might particularly benefit from CT screening.

Lung function impairment in lung cancer screening: discordance between risk and screening outcomes when looking through a PRISm

“…Those in the PRISm group had more aggressive (or advanced) lung cancer as suggested by lower rates of stage 1–2 disease at diagnosis, a higher prevalence of squamous cell and NSCLC-NOS and less adenocarcinoma (“Histology shift”). These findings also accord with those reported in the LUSI study ( 6 ). In addition, those with PRISm had lower rates of surgery for their lung cancers which may relate to the greater cardiovascular comorbid disease and more aggressive/advanced lung cancers ( Table 1 ).…”

“…When the ACRIN sub-cohort of the NLST (n=18,463) was subdivided into the same three mutually exclusive groups described by Kaaks and colleagues ( 6 ), the prevalence for the normal, AFL (COPD) and PRISm groups was 49.4%, 33.4% and 17.2% respectively. The higher rates of COPD and PRISm in the NLST compared to LUSI are expected given the older age and pack year eligibility requirement of the NLST ( Table 1 ).…”

“…Kaaks and colleagues stratified 2,029 subjects randomised to the computed tomography (CT) screening arm of their study ( 6 ), according to baseline pre-bronchodilator spirometry. They defined 3 mutually exclusive groups of screening participants, eligible according to age (50–69 years old) and smoking history (>15 pack years and quit <10 years), into those with airflow limitation (AFL) [chronic obstructive pulmonary disease (COPD), forced expiratory volume in 1 second/forced vital capacity (FEV 1 /FVC) <70%, n=369], preserved ratio impaired spirometry (PRISm; FEV 1 /FVC ≥70 and FEV 1 % predicted <80%, n=311) or normal spirometry (n=1,307).…”

Pulmonary emphysema and coronary artery calcifications at baseline LDCT and long-term mortality in smokers and former smokers of the ITALUNG screening trial

“…Investigation in larger samples, as well as external validation of the machine learning algorithm in independent samples, is worthy. In particular, the low number of deaths due to respiratory diseases, which is in line with other studies [4,41], did not allow us to assess the predictive value of emphysematous changes with respect to respiratory causes of death that have been observed in the NLST trial [11,13]. Second, although measurement of airway thickness is feasible in LDCT for LC screening [11,42], we did not perform it.…”

“…Cardio-vascular disease (CVD), lung cancer (LC), and respiratory diseases are the three main causes of death in smokers and former smokers undergoing low-dose computed tomography (LDCT) for LC screening [1][2][3][4]. The latter is currently recommended in the USA for subjects 50-80 years of age with a smoking history of at least 20 pack-years or who have quit in the past 15 years [5].…”