Lung transplantation for chronic obstructive pulmonary disease: A call to modify the lung allocation score to decrease waitlist mortality.

OBJECTIVE: Approximately 40% of lung transplants for chronic obstructive pulmonary disease (COPD) in the lung allocation score era are single lung transplantations (SLTs). We hypothesized that double lung transplantation (DLT) results in superior survival, but that mortality on the waitlist may compel clinicians to perform SLT. We investigated both waitlist mortality in COPD patients with restricted versus unrestricted listing preferences and posttransplant survival in SLT versus DLT to identify key predictors of mortality. METHODS: A retrospective analysis of waitlist mortality and posttransplant survival in patients with COPD was conducted using post-lung allocation score data from the United Network for Organ Sharing database between 2005 and 2018. RESULTS: Of 6740 patients with COPD on the waitlist, 328 (4.87%) died and 320 (4.75%) were removed due to clinical deterioration. Median survival on the waitlist was significantly worse in patients listed as restricted for DLT (4.39 vs 6.09 years; P = .002) compared with patients listed as unrestricted (hazard ratio, 1.34; 95% CI, 1.13-1.57). Factors that increase waitlist mortality include female sex, increased pulmonary artery pressure, and increased wait time. Median posttransplant survival was 5.3 years in SLT versus 6.5 years in DLT (P < .001). DLT recipients are younger, male patients with a higher lung allocation score. The survival advantage of DLT persisted in adjusted analysis (hazard ratio, 0.819; 95% CI, 0.741-0.905). CONCLUSIONS: Restricted listing preference is associated with increased waitlist mortality, but DLT recipients have superior posttransplant survival. Because the lung allocation score does not prioritize COPD, concern for increased waitlist mortality with restricted listing preference may drive continued use of SLT despite better posttransplant survival in DLT.

Impact of Chronic Obstruction Pulmonary Disease on Survival in Patients with Advanced Stage Lung Squamous Cell Carcinoma Undergoing Concurrent Chemoradiotherapy.

BACKGROUND: To date, no data are available regarding the effect of chronic obstruction pulmonary disease (COPD) and COPD with acute exacerbation (COPDAE) on survival in patients with lung squamous cell carcinoma (SCC) receiving definitive concurrent chemoradiotherapy (CCRT). PATIENTS AND METHODS: We enrolled 3986 patients with clinical stage IIIA-IIIB, unresectable lung SCC, who had received standard definitive CCRT, and categorized them into two groups based on their COPD status to compare overall survival outcomes. We also examined the effects of COPD severity (0, 1, or ≥2 hospitalizations for COPDA within 1 year before CCRT). RESULTS: In the inverse probability of treatment weighting (IPTW)-adjusted model, the adjusted hazard ratio (aHR) (95% confidence interval (CI)) of all-cause death for COPD was 1.04 (1.01, 1.16), compared no COPD in patients with stage IIIA-IIIB lung SCC receiving definitive CCRT. In the IPTW-adjusted model, the aHRs (95% CIs) of 1 and ≥ 2 hospitalizations for COPDAE within 1 year before CCRT were 1.32 (1.19, 1.46) and 1.81 (1.49, 2.19) respectively, compared with no hospitalization for COPDAE. CONCLUSION: COPD and its severity are significant independent risk factors for all-cause death in patients with stage IIIA-IIIB lung SCC receiving definitive CCRT. Hospitalization for COPDAE within 1 year before CCRT is the significant independent risk factor for lung cancer death in the patients with stage IIIA-IIIB lung SCC receiving definitive CCRT.

Clinical Utility of Central and Peripheral Airway Nitric Oxide in Aging Patients with Stable and Acute Exacerbated Chronic Obstructive Pulmonary Disease.

PURPOSE: Exhaled nitric oxide has been used as a marker of airway inflammation. The NO concentration in the central and peripheral airway/alveolar can be measured by a slow and fast exhalation flow rate to evaluate inflammation in different divisions within the respiratory tract. We hypothesized that FeNO200 (exhaled NO at a flow rate of 200mL/s) could be used as an evaluation tool for peripheral airway/alveolar inflammation and corticosteroid therapy in chronic obstructive pulmonary disease (COPD) patients. METHODS: We recruited 171 subjects into the study: 73 healthy controls, 59 stable COPD patients, and 39 acute exacerbations of COPD (AECOPD) patients. Exhaled nitric oxide (FeNO50 (exhaled NO at a flow rate of 50mL/s)), FeNO200 and CaNO (peripheral concentration of NO/alveolar NO) and clinical variables including pulmonary function, COPD Assessment Test (CAT), C-reactive protein concentration (CRP) and circulating eosinophil count were measured among the recruited participants. FeNO50, FeNO200 and CaNO were repeatedly evaluated in 39 AECOPD patients after corticosteroid treatment. RESULTS: FeNO200 was significantly higher in stable COPD and AECOPD patients than in healthy controls. Nevertheless, CaNO could not differentiate COPD from healthy controls. No correlation was found between circulating eosinophil counts or FEV1 and exhaled nitric oxide (FeNO50, FeNO200, CaNO) in COPD patients. For AECOPD patients, 64% of patients had eosinophil counts >100 cells/µL; 59% of patients had FeNO200 >10 ppb; only 31% of patients had FeNO50 > 25 ppb. Among AECOPD patients, the high FeNO50 and FeNO200 groups' levels were significantly lower than their baseline levels, and significant improvements in CAT were seen in the two groups after corticosteroid treatment. These implied a good corticosteroid response in AECOPD patients with FeNO200>10ppb. CONCLUSION: FeNO200 is a straightforward and feasible method to evaluate the peripheral NO concentration in COPD. FeNO200 can be a type 2 inflammation biomarker and a useful tool for predicting corticosteroid therapy in COPD.

Associations of marijuana with markers of chronic lung disease in people living with HIV.

OBJECTIVES: The relationship between marijuana use and markers of chronic lung disease in people living with HIV (PLWH) is poorly understood. METHODS: We performed a cross-sectional analysis of the Examinations of HIV-Associated Lung Emphysema (EXHALE) study, including 162 HIV-positive patients and 138 participants without HIV. We modelled marijuana exposure as: (i) current daily or weekly marijuana smoking vs. monthly or less often; or (ii) cumulative marijuana smoking (joint-years). Linear and logistic regression estimated associations between marijuana exposure and markers of lung disease, adjusted for tobacco smoking and other factors. RESULTS: In PLWH, current daily or weekly marijuana use was associated with a larger forced vital capacity (FVC), larger total lung capacity and increased odds of radiographic emphysema compared with marijuana non-smokers in adjusted models; these associations were not statistically significant in participants without HIV. Marijuana joint-years were associated with higher forced expiratory volume in 1 s and FVC in PLWH but not with emphysema. CONCLUSIONS: In PLWH, marijuana smoking was associated with higher lung volumes and potentially with radiographic emphysema. No consistently negative associations were observed between marijuana and measures of chronic lung health.

What can be done to impact respiratory inhaler misuse: exploring the problem, reasons, and solutions.

INTRODUCTION: Respiratory inhalers, when used correctly, provide critical treatments for managing pulmonary conditions. However, many patients misuse inhalers, negatively affecting disease control, quality of life, healthcare utilization, and costs. Numerous factors are associated with misuse and are nested within four levels of influence: individual, interpersonal, organizational/institutional, and policy. AREAS COVERED: This review analyzed published literature and identified the most salient factors at each socio-ecological framework level. English language articles from any year were identified from PubMed, Google Scholar, and Embase databases. Misuse exists across clinical settings, patient populations, and device types. Several potential solutions are highlighted. Published interventions to improve inhaler technique have utilized handouts, in-person, virtual, and biofeedback approaches both inside and outside of healthcare settings with varied effectiveness. However, some interventions have superior effectiveness for improving technique and reducing acute care utilization. EXPERT OPINION: To robustly address inhaler misuse, future solutions should focus on multi-level approaches to account for the myriad of factors contributing to inhaler misuse. Solutions should also streamline inhaler equipment, identify innovative technology-based solutions, support collaborations across healthcare and non-healthcare settings, and ensure reimbursement to healthcare professionals for inhaler education. Rigorous research studies must be funded and supported to identify and disseminate solutions.

Pulmonary delivery of Nanocomposite Microparticles (NCMPs) incorporating miR-146a for treatment of COPD.

The treatment and management of COPD by inhalation to the lungs has emerged as an attractive alternative route to oral dosing due to higher concentrations of the drug being administered to site of action. In this study, Nanocomposite Microparticles (NCMPs) of microRNA (miR-146a) containing PGA-co-PDL nanoparticles (NPs) for dry powder inhalation were formulated using l-leucine and mannitol. The spray-drying (Buchi B290) process was optimised and used to incorporate NPs into NCMPs using mix of l-leucine and mannitol excipients in different ratios (F1; 100:0% w/w, F2; 75:25% w/w, F3; 50:50% w/w, F4; 25:75% w/w, F5; 0:100% w/w) to investigate yield %, moisture content, aerosolisation performance and miR-146a biological activity. The optimum condition was performed at feed rate 0.5 ml/min, aspirator rate 28 m3/h, atomizing air flow rate 480 L/h, and inlet drying temperature 70 °C which produced highest yield percentage and closest recovered NPs size to original prior spray-drying. The optimum formulation (F4) had a high yield (86.0 ±â€¯15.01%), recovered NPs size after spray-drying 409.7 ±â€¯10.05 nm (initial NPs size 244.8 ±â€¯4.40 nm) and low moisture content (2.02 ±â€¯0.03%). The aerosolisation performance showed high Fine Particle Fraction (FPF) 51.33 ±â€¯2.9%, Emitted Dose (ED) of 81.81 ±â€¯3.0%, and the mass median aerodynamic diameter (MMAD) was ≤5 µm suggesting a deposition in the respirable region of the lungs. The biological activity of miR-146a was preserved after spray-drying process and miR-146a loaded NCMPs produced target genes IRAK1 and TRAF6 silencing. These results indicate the optimal process parameters for the preparation of NCMPs of miR-146a-containing PGA-co-PDL NPs suitable for inhalation in the treatment and management of COPD.

Experiences of patients undergoing pulmonary rehabilitation during an exacerbation of chronic respiratory disease.

Chronic obstructive pulmonary disease (COPD) is characterized in the later stages by acute exacerbations that often require hospitalization. Pulmonary rehabilitation is recommended for patients with COPD to aid symptom control, improve quality of life and increase physical activity. We have previously reported a large intervention trial commenced during a hospital admission. The aim of this sub-study was to evaluate the patients' experiences of discharge following the hospitalization for an acute exacerbation of COPD. During a programme of early rehabilitation (ER) patient perceptions, experiences and healthcare use were collated during the month that followed their discharge. ER (started during their admission) was comprised of exercise training techniques that were modified to suit the environment of acute illness, together with an education and self-management programme. Each patient was then supported on the programme by telephone contact, following their discharge home, at 48 hours, 2 weeks and 4 weeks. We collected information in relation to the walking and exercise progression; we monitored patient recall of healthcare use, compliance/understanding of medical therapy, as well as their wider perceptions that may have influenced the recovery process. Healthcare use was captured using GP records and data analysis. Of the 100 patients, 47 males, (mean (standard deviation)) 71 (9.3) years, FEV1 1.14 L (0.6), BMI 26.6 (6.9), pack smoked years 45.8 (29.6), ethnicity White British 97%, were discharged home following an acute exacerbation of their respiratory symptoms, to an ER programme. At 48 hours following discharge, a minority (20%) of patients stated their symptoms were 'feeling better'; 15% highlighted that they found the prescribed 'exercise difficult'; 44% of patients felt at the end of the month that prescribed exercise programme had a 'positive effect' on their recovery from their exacerbation; 38% of patients felt their family had a positive effect on their recovery; 11% felt their family hindered. Patients reported a mean confidence score of 8.21 (2.1) for exercise that did not vary over the three contacts ( p = 0.166). A similar mean confidence score of 7.76 (2.6) was reported for walking with a non-statistical change also noted ( p = 0.223). When patient recall of primary health care contact was compared with actual use, there was statistical significance shown ( p = 0.002); patients underestimated the amount of care they received. The data indicate that patients do recover at home within the support of an early intervention. Patients are positive about the benefit of ER in the process of recovery; however, this is uncontrolled data.

[Nutritional abnormalities in chronic obstructive pulmonary disease]. / Alteraciones nutricionales en la enfermedad pulmonar obstructiva crónica.

Nutritional abnormalities are associated with chronic obstructive pulmonary disease with a frequency ranging from 2 to 50%, depending on the geographical area and the study design. Diagnostic tools include anthropometry, bioelectrical impedance, dual energy radioabsortiometry and deuterium dilution, being the body mass and the lean mass indices the most frequently used parameters. While the most important consequences of nutritional abnormalities are muscle dysfunction and exercise limitation, factors implicated include an imbalance between caloric intake and consumption, and between anabolic and catabolic hormones, inflammation, tobacco smoking, poor physical activity, hypoxemia, some drugs and aging/comorbidities. The most important molecular mechanism for malnutrition associated with chronic obstructive pulmonary disease appears to be the mismatching between protein synthesis and breakdown. Among the therapeutic measures proposed for these nutritional abnormalities are improvements in lifestyle and nutritional support, although the use of anabolic drugs (such as secretagogues of the growth hormone) offers a new therapeutic strategy.