Safe and effective use of nivolumab for treating lung adenocarcinoma associated with sporadic lymphangioleiomyomatosis: a rare case report.

BACKGROUND: Sporadic lymphangioleiomyomatosis (LAM) is a rare form of diffuse parenchymal lung disease. PD-1 blocking antibodies constitute an essential treatment option for advanced non-small-cell lung cancer (NSCLC). The effect of immune checkpoint inhibitors in lymphangioleiomyomatosis patients with non-small cell lung cancer is unknown: concomitant symptomatic interstitial lung disease or the use of immunosuppressors was a key exclusion criterion in the original studies of immune checkpoint inhibitors, especially regarding the risk of interstitial lung disease exacerbation. CASE PRESENTATION: A 48-year-old female, active smoker (36 pack-years), diagnosed with sporadic LAM since 2004 suffered from metastatic adenocarcinoma of the lung. Third-line therapy with nivolumab was started in 2015, with a major partial response. Due to pulmonary function alterations, sirolimus was also reinitiated in 2017 in conjunction with nivolumab, without any undesirable effects and a major partial response continuing up to May 2018. CONCLUSIONS: This case highlights the safe and effective use of nivolumab for managing metastatic lung adenocarcinoma that occurred in a patient with sporadic LAM. In the current case, immunotherapy proved highly successful in managing the NSCLC tumor that occurred upon LAM follow-up, with both a significantly prolonged partial response and acceptable safety profile.

Dyspnea-induced Limitation (DYSLIM), a new self-administered concise questionnaire to evaluate dyspnea-related activity limitation in chronic respiratory diseases.

BACKGROUND AND AIM: Few questionnaires are available for routine assessment of dyspnea. The study aimed to design a self-administered questionnaire assessing the impact of chronic dyspnea on daily activities, named DYSLIM (Dyspnea-induced Limitation). METHODS: The development followed 4 steps: 1: selection of relevant activities and related questions (focus groups); 2: clinical study: internal and concurrent validity vs. modified Medical Research Council (mMRC), Baseline Dyspnea Index (BDI) and Saint George Respiratory Questionnaire (SGRQ); 3: item reduction; 4: responsiveness. Eighteen activities (from eating to climbing stairs) were considered with 5 modalities for each: doing the task slowly, taking breaks, seeking assistance, changing habits, and activity avoidance. Each modality was graded from 5 (never) to 1 (very often). Validation study included 194 patients: COPD (FEV1 ≥ 50% pred: n = 40; FEV1 < 50% pred: n = 65); cystic fibrosis (n = 30), interstitial lung disease (n = 30), pulmonary hypertension (n = 29). Responsiveness was evaluated by post-pulmonary rehabilitation data in 52 COPD patients. RESULTS: Acceptability was high and short term (7 days) reproducibility was satisfactory (Kappa mostly above 0.7). Concurrent validity was high vs. mMRC (Spearman correlation coefficient, r = 0.71), BDI (r = - 0.75) and SGRQ (r = - 0.79). The reduced questionnaire with 8 activities (from cleaning to climbing stairs) and 3 modalities (slowly, seeking help, changing habits) showed a comparable validity and was chosen as the final short version. Effect size of rehabilitation was good for both the full (0.57) and short (0.51) versions. A significant correlation was also found between changes of SGRQ and DYSLIM post rehabilitation: r = - 0.68 and r = - 0.60 for full and reduced questionnaires, respectively. CONCLUSION: The DYSLIM questionnaire appears promising for the evaluation of dyspnea-induced limitations in chronic respiratory diseases and seems suitable for use in various contexts.

2022 Update of indications and contraindications for lung transplantation in France.

Lung transplantation (LTx) is a steadily expanding field. The considerable developments have been driven over the years by indefatigable work conducted at LTx centers to improve donor and recipient selection, combined with multifaceted efforts to overcome challenges raised by the surgical procedure, perioperative care, and long-term medical complications. One consequence has been a pruning away of contraindications over time, which has, in some ways, complicated the patient selection process. The Francophone Pulmonology Society (Société de Pneumology de Langue Française, SPLF) set up a task force to produce up-to-date working guidelines designed to assist pulmonologists in managing end-stage respiratory insufficiency, determining which patients may be eligible for LTx, and appropriately timing LTx-center referral. The task force examined the most recent literature and evaluated the risk factors that limit patient survival after LTx. Ideally, the objectives of LTx are to prolong life while also improving quality of life. The guidelines developed by the task force apply to a limited resource and are consistent with the ethical principles described below.

Glucocorticoids with low-dose anti-IL1 anakinra rescue in severe non-ICU COVID-19 infection: A cohort study.

BACKGROUND: The optimal treatment for patients with severe coronavirus-19 disease (COVID-19) and hyper-inflammation remains debated. MATERIAL AND METHODS: A cohort study was designed to evaluate whether a therapeutic algorithm using steroids with or without interleukin-1 antagonist (anakinra) could prevent death/invasive ventilation. Patients with a ≥5-day evolution since symptoms onset, with hyper-inflammation (CRP≥50mg/L), requiring 3-5 L/min oxygen, received methylprednisolone alone. Patients needing ≥6 L/min received methylprednisolone + subcutaneous anakinra daily either frontline or in case clinical deterioration upon corticosteroids alone. Death rate and death or intensive care unit (ICU) invasive ventilation rate at Day 15, with Odds Ratio (OR) and 95% CIs, were determined according to logistic regression and propensity scores. A Bayesian analysis estimated the treatment effects. RESULTS: Of 108 consecutive patients, 70 patients received glucocorticoids alone. The control group comprised 63 patients receiving standard of care. In the corticosteroid±stanakinra group (n = 108), death rate was 20.4%, versus 30.2% in the controls, indicating a 30% relative decrease in death risk and a number of 10 patients to treat to avoid a death (p = 0.15). Using propensity scores a per-protocol analysis showed an OR for COVID-19-related death of 0.9 (95%CI [0.80-1.01], p = 0.067). On Bayesian analysis, the posterior probability of any mortality benefit with corticosteroids+/-anakinra was 87.5%, with a 7.8% probability of treatment-related harm. Pre-existing diabetes exacerbation occurred in 29 of 108 patients (26.9%). CONCLUSION: In COVID-19 non-ICU inpatients at the cytokine release phase, corticosteroids with or without anakinra were associated with a 30% decrease of death risk on Day 15.

Daily life physical activity in patients with chronic stage IV sarcoidosis: A multicenter cohort study.

BACKGROUND AND OBJECTIVES: Little is known about the consequences of chronic sarcoidosis on daily life physical activity (DLPA). The aim of this prospective study was to measure DLPA in patients with chronic sarcoidosis and to determine its relationship to clinical and functional parameters. METHODS: Fifty-three patients with chronic sarcoidosis and 28 healthy control subjects were enrolled in this multicenter prospective study. Two markers of DLPA (number of steps walked per day [SPD]) and total daily energy expenditure (TEE) were assessed for five consecutive days with a physical activity monitor. Pulmonary function, aerobic capacity (maximal oxygen uptake [VO2max]), exercise capacity (6-min walk test [6MWT]), and quality of life (self-reported questionnaires) were also evaluated. Comparisons of DLPA parameters between the two groups were performed using an analysis of covariance adjusted for age, sex, and body mass index (BMI). Relationships between DLPA parameters and patient characteristics were assessed in multivariable linear regression models. RESULTS: Patients with sarcoidosis walked significantly fewer SPD than did the control subjects (6395 ± 4119 and 11 817 ± 3600, respectively; P < 0.001 after adjustment for age, BMI, and sex). TEE was not significantly different between patients with sarcoidosis and healthy controls (median [interquartile range]: 2369 [2004-2827] and 2387 [2319-2876] kcal/day, respectively, P = 0.054 adjusted for age, BMI, and sex). SPD showed significant positive correlations with 6MWT distance (Pearson's correlation, r = 0.32, 95% confidence intervals [95%CI] = 0.06, 0.55; P = 0.019), VO2max (r = 0.44, 95%CI = 0.17, 0.65; P = 0.002), and Visual Simplified Respiratory Questionnaire score (r = 0.44, 95%CI = 0.19, 0.64; P = 0.001), and a significant negative correlation with modified Medical Research Council questionnaire score (r = -0.38, 95%CI = -0.60, -0.10; P = 0.009). TEE was significantly correlated with BMI (r = 0.38, 95%CI = 0.13, 0.59; P = 0.004), forced expiratory volume in 1 second (r = 0.55, 95%CI = 0.33, 0.71; P < 0.001), total lung capacity (r = 0.44, 95%CI = 0.18, 0.64; P = 0.001), and forced vital capacity (r = 0.56, 95%CI = 0.34, 0.72; P < 0.001). In multivariable analysis, SPD remained associated only with VO2max. CONCLUSION: Patients with chronic sarcoidosis appear to have reduced DLPA mainly because of compromised VO2max.