IL-10 producing regulatory B cells are decreased in blood from smokers and COPD patients.

BACKGROUND: Two opposing B cell subsets have been defined based on their cytokine profile: IL-6 producing effector B cells (B-effs) versus IL-10 producing regulatory B cells (B-regs) that respectively positively or negatively regulate immune responses. B-regs are decreased and/or impaired in many autoimmune diseases and inflammatory conditions. Since there is increasing evidence that links B cells and B cell-rich lymphoid follicles to the pathogenesis of COPD, the aim of this study was to investigate the presence and function of B-regs in COPD. METHODS: First, presence of IL-10 producing regulatory B cells in human lung tissue was determined by immunohistochemistry. Secondly, quantification of IL-10 + B-regs and IL-6 + B-effs in peripheral blood mononuclear cells (PBMCs) from healthy controls, smokers without airflow limitation, and COPD patients (GOLD stage I-IV) was performed by flow cytometry. Thirdly, we exposed blood-derived B cells from COPD patients in vitro to cigarette smoke extract (CSE) and quantified IL-10 + B-regs and IL-6 + B-effs. Furthermore, we aimed at restoring the perturbed IL10 production by blocking BAFF. Fourthly, we determined mRNA expression of transcription factors involved in IL-10 production in FACS sorted memory- and naive B cells upon exposure to medium or CSE. RESULTS: The presence of IL-10 producing regulatory B cells in parenchyma and lymphoid follicles in lungs was confirmed by immunohistochemistry. The percentage of IL-10 + B-regs was significantly decreased in blood-derived memory B cell subsets from smokers without airflow limitation and patients with COPD, compared to never smokers. Furthermore, the capacity of B cells to produce IL-10 was reduced upon in vitro exposure to CSE and this could not be restored by BAFF-blockade. Finally, upon CSE exposure, mRNA levels of the transcription factors IRF4 and HIF-1α, were decreased in memory B cells. CONCLUSION: Decreased numbers and impaired function of B-regs in smokers and patients with COPD might contribute to the initiation and progression of the disease.

Effects of Whole Body Vibration in Patients With COPD.

BACKGROUND: Whole body vibration training (WBVT) improves muscle force in healthy subjects. Resistance training (RT) is an important component of a pulmonary program. AIM: To investigate the effects of either 12 weeks WBVT or RT, both provided after 15 min of aerobic training as warming up. METHODS: COPD patients, referred for pulmonary rehabilitation, were randomized to either a WBVT or a conventional RT group. Primary outcome was the change in 6 Minute Walking Distance (6MWD) after 12 weeks. Maximum exercise capacity (Wmax), quadriceps force (QF), quality of life (QoL) and number of responders, defined as the percentage of patients reaching the minimally clinically important difference (MCID) for the aforementioned outcome measurements were the secondary outcomes. Data are expressed as medians (interquartile range). RESULTS: 62 patients with COPD were included. After WBVT, 6MWD improved by 35 (-14-76) m (p = 0.003), Wmax by 7 (2-23) Watt (p = 0.001), QoL by 13 (4-25) points (p = 0.002) and QF by 9 (-16-29) Nm (NS). In the RT-group, 6MWD, Wmax, QoL and QF increased significantly, with 60 (-13-96) m (p < 0.001), 12 (8-18) Watt (p < 0.001), 11 (3-16) points (p = 0.002) and 12 (-3-44) Nm (p = 0.009), respectively. The MCID for 6MWD (54 m) was reached by 8/26 patients in the WBVT-group and by 16/25 patients in RT-group (p = 0.05). No significant differences between groups were observed for the primary and secondary outcomes. CONCLUSIONS: WBVT after 15 min aerobic training enhances 6MWD, Wmax and QoL in COPD patients; however only 30% of patients reached the MCID for 6MWD.

Prospective longitudinal evaluation of hospitalised COVID-19 survivors 3 and 12 months after discharge.

Background: Long-term outcome data of coronavirus disease 2019 (COVID-19) survivors are needed to understand their recovery trajectory and additional care needs. Methods: A prospective observational multicentre cohort study was carried out of adults hospitalised with COVID-19 from March through May 2020. Workup at 3 and 12 months following admission consisted of clinical review, pulmonary function testing, 6-min walk distance (6MWD), muscle strength, chest computed tomography (CT) and quality of life questionnaires. We evaluated factors correlating with recovery by linear mixed effects modelling. Results: Of 695 patients admitted, 299 and 226 returned at 3 and 12 months, respectively (median age 59 years, 69% male, 31% severe disease). About half and a third of the patients reported fatigue, dyspnoea and/or cognitive impairment at 3 and 12 months, respectively. Reduced 6MWD and quadriceps strength were present in 20% and 60% at 3 months versus 7% and 30% at 12 months. A high anxiety score and body mass index correlated with poor functional recovery. At 3 months, diffusing capacity for carbon monoxide (D LCO) and total lung capacity were below the lower limit of normal in 35% and 18%, decreasing to 21% and 16% at 12 months; predictors of poor D LCO recovery were female sex, pre-existing lung disease, smoking and disease severity. Chest CT improved over time; 10% presented non-progressive fibrotic changes at 1 year. Conclusion: Many COVID-19 survivors, especially those with severe disease, experienced limitations at 3 months. At 1 year, the majority showed improvement to almost complete recovery. To identify additional care or rehabilitation needs, we recommend a timely multidisciplinary follow-up visit following COVID-19 admission.

Implicit attitudes towards smoking predict long-term relapse in abstinent smokers.

RATIONALE: It has previously been argued that implicit attitudes toward substance-related cues drive addictive behavior. Nevertheless, it remains an open question whether behavioral markers of implicit attitude activation can be used to predict long-term relapse. OBJECTIVES: The main objective of this study was to examine the relationship between implicit attitudes toward smoking-related cues and long-term relapse in abstaining smokers. METHODS: Implicit attitudes toward smoking-related cues were assessed by means of the Implicit Association Test (IAT) and the evaluative priming task (EPT). Both measures were completed by a group of smokers who volunteered to quit smoking (patient group) and a group of nonsmokers (control group). Participants in the patient group completed these measures twice: once prior to smoking cessation and once after smoking cessation. Relapse was assessed by means of short telephone survey, 6 months after completion of the second test session. RESULTS: EPT scores obtained prior to smoking cessation were related to long-term relapse and correlated with self-reported nicotine dependence as well as daily cigarette consumption. In contrast, none of the behavioral outcome measures were found to correlate with the IAT scores. CONCLUSIONS: These findings corroborate the idea that implicit attitudes toward substance-related cues are critically involved in long-term relapse. A potential explanation for the divergent findings obtained with the IAT and EPT is provided.

Rehabilitation in patients with radically treated respiratory cancer: A randomised controlled trial comparing two training modalities.

INTRODUCTION: The evidence on the effectiveness of rehabilitation in lung cancer patients is limited. Whole body vibration (WBV) has been proposed as an alternative to conventional resistance training (CRT). METHODS: We investigated the effect of radical treatment (RT) and of two rehabilitation programmes in lung cancer patients. The primary endpoint was a change in 6-min walking distance (6MWD) after rehabilitation. Patients were randomised after RT to either CRT, WBVT or standard follow-up (CON). Patients were evaluated before, after RT and after 12 weeks of intervention. RESULTS: Of 121 included patients, 70 were randomised to either CON (24), CRT (24) or WBVT (22). After RT, 6MWD decreased with a mean of 38m (95% CI 22-54) and increased with a mean of 95m (95% CI 58-132) in CRT (p<0.0001), 37m (95% CI -1-76) in WBVT (p=0.06) and 1m (95% CI -34-36) in CON (p=0.95), respectively. Surgical treatment, magnitude of decrease in 6MWD by RT and allocation to either CRT or WBVT were prognostic for reaching the minimally clinically important difference of 54m increase in 6MWD after intervention. CONCLUSIONS: RT of lung cancer significantly impairs patients' exercise capacity. CRT significantly improves and restores functional exercise capacity, whereas WBVT does not fully substitute for CRT.

Quantitative Perfusion Scintigraphy or Anatomic Segment Method in lung cancer resection.

BACKGROUND: Quantitative Perfusion Scintigraphy (QPS) and Anatomic Segment Method (ASM) are two techniques for estimating postoperative pulmonary function. QPS is gold standard, but holds disadvantages. AIM: Could ASM substitute QPS in the preoperative work-up of NSCLC? METHODS: Retrospective study in patients with NSCLC or mesothelioma undergoing resection. FEV1 and DL,CO were estimated by QPS and ASM and compared to pulmonary function measured 3 months after resection. Correlation tests and Bland-Altman analyses were performed. RESULTS: 40 patients (23 lobectomies, 14 pneumonectomies). Both methods correlated similarly with postoperative FEV(1) (QPSρ=0.69; ASMρ=0.75) and DL,CO (QPSρ=0.70; ASMρ=0.74). Correlation between both methods was high (ppoFEV(1)ρ=0.89; ppoDL,COρ=0.89). The same principles applied in a subgroup analysis of patients with COPD. Bland-Altman analyses showed that ASM underestimated postoperative FEV(1) and DL,CO more than QPS in all groups. CONCLUSION: QPS and ASM are remarkably similar in predicting postoperative pulmonary function. As ASM underestimates pulmonary function more, it could be a safe alternative from a cost-benefit point of view. Based on these results, it appears that QPS could be restricted to patients in whom ASM suggests functional inoperability, although further prospective studies are necessary.

Effects of pulmonary rehabilitation in patients with restrictive lung diseases.

BACKGROUND: Pulmonary rehabilitation programs improve exercise tolerance, muscle strength, and dyspnea in patients with COPD. The aim of the study was to assess prospectively the effectiveness and feasibility of pulmonary rehabilitation in patients with restrictive lung diseases. METHODS: In a prospective, nonrandomized, noncontrolled study, patients with an established diagnosis of restrictive lung disease (RLD) participated in a 24-week outpatient multidisciplinary rehabilitation program. Pulmonary function, exercise capacity, muscle force, and dyspnea were measured at inclusion, after 12 and 24 weeks of rehabilitation. Primary outcome was the change in 6-min walk distance (6MWD) after 12 weeks of rehabilitation. RESULTS: Twenty-nine patients out of 31 patients (57 +/- 17 years of age; 21 men; FEV(1): 1.4 +/- 0.7 L) completed the 12-week rehabilitation program and 26 patients the 24-week rehabilitation program. At inclusion, exercise tolerance (maximal oxygen consumption [V(O(2))max]: 63% +/- 27% predicted; 6MWD: 390 +/- 140 m) and quadriceps force ([QF] 61% +/- 21% predicted) were reduced, and dyspnea, assessed using the Chronic Respiratory Disease Questionnaire (CRDQ), was increased (CRDQ item dyspnea [CRDQd]: 16 +/- 6 points). Exercise capacity, muscle force, and CRDQd improved significantly after 12 weeks (6MWD: 445 +/- 142 m; V(O(2))max: 69% +/- 30% predicted; QF: 73% +/- 25% predicted; CRDQd: 20 +/- 6 points) (P < .05). Further improvements were noted after 24 weeks (6MWD: 463 +/- 146 m; CRDQd: 22 +/- 6 points). CONCLUSIONS: Patients with RLD respond well after 12 weeks of pulmonary rehabilitation, and even better results were seen after 24 weeks. Clinically significant improvements were obtained in the majority of the patients after 24 weeks.

Genetic variation in three candidate genes and nicotine dependence, withdrawal and smoking cessation in hospitalized patients.

AIMS: This study evaluates the relationship of six polymorphisms found in the CHRNA3, DRD2 and COMT genes with nicotine dependence, the ability to quit smoking and the occurrence of withdrawal symptoms after short-term use of nicotine patch in hospitalized patients. MATERIALS & METHODS: The study included 233 participants from a double-blind, placebo-controlled trial of nicotine patch substitution with a 6-month follow-up period. Nicotine dependence was assessed by the Fagerström Test for Nicotine Dependence (FTND) questionnaire, withdrawal symptoms by the Minnesota Nicotine Withdrawal Scale questionnaire and smoking cessation by self-reported abstinence at 1 week, 1 month and 6 months after treatment. RESULTS: After correcting for multiple testing, three polymorphisms in the DRD2 gene (Taq1A, Taq1B and Pro319Pro) were significantly associated with nicotine dependence (p = 0.018, p = 0.048 and p = 0.006, respectively). Using a cutoff point for the FTND score, the CHRNA3 Tyr215Tyr (rs1051730) polymorphism was also associated with nicotine dependence (p = 0.037 and p = 0.074 after correction for multiple testing). No association of any of the studied polymorphisms was observed with either smoking cessation or the occurrence of withdrawal symptoms. CONCLUSION: This study confirms the reported association of the CHRNA3 locus with nicotine dependence and shows the involvement of two independent DRD2 polymorphisms in nicotine dependence.