Harnessing the immune system to fight cancer is an exciting advancement in lung cancer therapy. Anti-tumor immunity can be augmented by checkpoint blockade therapy, which removes the inhibition/brakes imposed on the immune system by the tumor. Checkpoint blockade therapy with anti-PD1/anti-PDL1 antibodies causes tumor regression in around 25% of lung cancer patients. In another approach, the immune system is forced or accelerated to attack the tumour, via augmentation of the anti-tumour response against mutations carried by each lung tumour. This latter approach has become feasible since the advent of next generation sequencing technology, which allows identification of the specific mutations that each individual lung tumor bears. Indeed lung cancers are now known to have high mutation rates, making them logical targets for mutation-directed immune therapies.

We review how sequencing of lung cancer mutations leads to better understanding of how the immune system recognizes tumors, providing improved opportunities to track anti-tumor immunity, and ultimately the development of personalized vaccine strategies aimed at unleashing the host immune system to attack mutations in the tumor.

INTRODUCTION: Many extrathoracic malignancies can metastasize to lungs and mediastinal lymph nodes. Whether mediastinal lesions are metastasis in these patients changes staging, prognosis, and treatment strategy. In this study, we aimed to find out the contribution of EBUS-TBNA to the diagnosis in cases with extrathoracic malignancy.

MATERIALS AND METHODS: Patients who had been previously diagnosed as extrapulmonary solid organ malignancy and in whom mediastinal or hilar lymphadenopathy developed during their follow-up and EBUS-TBNA was applied for diagnostic purposes were retrospectively included in this study.

RESULTS: A total of 91 patients consisting of 35 females (38.5 %) and 56 males (61.5 %) were included in the study. The mean age of the patients was 60.5 (±11.4). Malignancy was not observed in 54 (59.3 %) patients; primary malignancy metastasis was detected in 33 (36.3 %) patients, and primary lung cancer was detected in 4 (4.4 %) patients with EBUS-TBNA. The sensitivity of EBUS-TBNA in extrathoracic malignancies was determined as 90.2 %; its specificity was determined as 100 %, its negative predictive value as 92.5 %, its positive predictive value as 100 %, and its diagnostic accuracy as 95.6 %. The highest rate was determined in the left lower paratracheal lymph node when they were examined in terms of malignancy detection rate in lymph node stations.

CONCLUSION: EBUS-TBNA is a minimally invasive method with quite a low complication rate that does not require general anesthesia. It should be the first step method to be used in the diagnosis of mediastinal and hilar lymphadenopathies seen in extrathoracic malignancies since it has high diagnostic accuracy, sensitivity, and specificity. EBUS-TBNA significantly reduces the need for surgical intervention. Further surgical interventions can be planned in patients in whom diagnostic competence is not ensured.

A Multicenter Randomized Trial Assessing the Efficacy of Helium/Oxygen in Severe Exacerbations of Chronic Obstructive Pulmonary Disease.

Am J Respir Crit Care Med. 2016 Oct 13;

Authors: Jolliet P, Ouanes-Besbes L, Abroug F, Ben Khelil J, Besbes M, Garnero A, Arnal JM, Daviaud F, Chiche JD, Lortat-Jacob B, Diehl JL, Lerolle N, Mercat A, Razazi K, Brun-Buisson C, Durand-Zaleski I, Texereau J, Brochard L, E.C.H.O.^ICU trial investigators

Abstract
RATIONALE: During non-invasive ventilation (NIV) for COPD exacerbations, Helium/Oxygen (He/O2) reduces work of breathing and hypercapnia more than Air/O2 but impact on clinical outcome remains unknown.
OBJECTIVE: To determine whether continuous administration of He/O2 for 72 hours, during and in-between NIV sessions, is superior to Air/O2 in reducing NIV failure (25% to 15%) in severe hypercapnic COPD exacerbations.
METHODS: Prospective, randomized, open-label trial (16 intensive care units, 6 countries).
INCLUSION CRITERIA: COPD exacerbations with PaCO2 ≥ 45 mmHg, pH ≤ 7.35, and at least one: respiratory rate ≥ 25/min, PaO2 ≤ 50 mmHg, SpO2 ≤ 90%. A 6-month follow-up was performed.
OUTCOMES: Main: NIV failure (intubation or death without intubation in ICU). Secondaries: physiological parameters, duration of ventilation, ICU and hospital stay, 6-month recurrence and rehospitalization rates.
MAIN RESULTS: Trial stopped prematurely (445 randomized patients) for a low global failure rate. NIV failure: Air/O2 14.5% (N=32), He/O2 14.7% (N=33, p=0.97). Time to NIV failure: He/O2 group 93 hours (N=33), Air/O2 group 52 hours (N=32, p=0.12). Respiratory rate, pH, PaCO2 and encephalopathy score improved significantly faster with He/O2. ICU stay was comparable between groups. In patients intubated after failing NIV, He/O2 patients had a shorter ventilation duration (7.4±7.6 vs 13.6±12.6 d, p = 0.02) and ICU stay (15.8±10.9 vs 26.7±21.0 days, p = 0.01). No difference was observed in ICU and 6-month mortality.
CONCLUSIONS: He/O2 improves respiratory acidosis, encephalopathy and respiratory rate more quickly than Air/O2 but does not prevent NIV failure. Overall, the rate of NIV failure is low. Clinical trial registration available at www.clinicaltrials.gov, ID NCT01155310.

PMID: 27736154 [PubMed - as supplied by publisher]

Effectiveness of a pharmacist-driven intervention in COPD (EPIC): study protocol for a randomized controlled trial.

Trials. 2016 Oct 13;17(1):502

Authors: Davis E, Marra C, Gamble JM, Farrell J, Lockyer J, FitzGerald JM, Abu-Ashour W, Gillis C, Hawboldt J

Abstract
BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) are often nonadherent with medications and have poor inhaler technique. Community pharmacists can help to improve health-related quality of life and overall outcomes in patients with COPD. We aim to measure the effectiveness of a systematic, pharmacist-driven intervention on patients with diagnosed COPD.
METHODS/DESIGN: This pragmatic, parallel-group, cluster randomized controlled trial is designed to determine the effectiveness of a multifactorial, pharmacist-led intervention on medication adherence, inhaler technique, health-related quality of life, health care resource utilization including COPD exacerbations, and use of medications. Participating pharmacies in Newfoundland and Labrador (NL), Canada will be randomly assigned to either the intervention or the control group. The intervention group will deliver an enhanced form of care that emphasizes COPD management. The control group will provide usual care and a COPD education pamphlet. Included patients will be aged 40 years or older, have a physician-confirmed diagnosis of COPD, and be able to answer questionnaires in English. The primary outcomes are the between-group difference in the change from baseline to 6 months in medication adherence using the Medication Possession Ratio (MPR) and the Morisky Medication Adherence Scale (MMAS-8). The secondary outcomes are also measured from baseline to 6 months, and include the proportion of patients with a clinically significant change in adherence, the proportion of patients defined as having "good adherence," the mean MPR between groups, quality of life as measured by the St. George's Respiratory Questionnaire, medication inhalation technique using a pharmacist-scored checklist, health care resource utilization and antibiotic and orally administered corticosteroid use for COPD exacerbations. Differences between groups will be analyzed at the individual patient level while controlling for clustering effect.
DISCUSSION: A pharmacist-led COPD intervention has the potential to improve patient medication adherence, thus increasing quality of life, possibly decreasing pulmonary exacerbations and reducing utilization of acute health care resources. Methods and results taken from this study could be used to enhance the delivery of COPD care by community pharmacists in a real-world setting. This would serve to enhance COPD population health and quality of life.
TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN) ISRCTN78138190 , registered on 3 February 2016.

PMID: 27737686 [PubMed - in process]