Caring for patients with advanced COPD: beyond the inhalers .

COPD affects millions of people worldwide. Patients with advanced COPD have a high symptom burden. Breathlessness, cough and fatigue are frequent daily symptoms. Guidelines often focus on pharmacological treatment, especially inhaler therapy, but other approaches in combination with medications offer symptomatic benefit. In this review, we take a multidisciplinary approach with contributions from pulmonary physicians, cardiothoracic surgeons and a physiotherapist. The following areas are addressed: oxygen therapy and noninvasive ventilation (NIV), dyspnoea management, surgical and bronchoscopic options, lung transplantation and palliative care. Oxygen therapy prescribed within guidelines improves mortality in patients with COPD. NIV guidelines offer only low-certainty instruction on the use of this therapy on the basis of the limited available evidence. Dyspnoea management can take place through pulmonary rehabilitation. Specific criteria aid decisions on referral for lung volume reduction treatments through surgical or bronchoscopic approaches. Lung transplantation requires precise disease severity assessment to determine which patients have the most urgent need for lung transplantation and are likely to have the longest survival. The palliative approach runs in parallel with these other treatments, focusing on symptoms and aiming to improve the quality of life of patients and their families facing the problems associated with life-threatening illness. In combination with appropriate medication and an individual approach to symptom management, patients' experiences can be optimised. Educational aims: To understand the multidisciplinary approach to management of patients with advanced COPD.To recognise the parallel approaches to oxygen, NIV and dyspnoea management with consideration of more interventional options with lung volume reduction therapy or lung transplantation.To understand the high level of symptomatology present in advanced COPD and the relevance of palliative care alongside optimal medical management.

Interventions to standardise hospital care at presentation, admission or discharge or to reduce unnecessary admissions or readmissions for patients with acute exacerbation of chronic obstructive pulmonary disease: a scoping review.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease that may be punctuated by episodes of worsening symptoms, called exacerbations. Acute exacerbations of COPD (AECOPD) are detrimental to clinical outcomes, reduce patient quality of life and often result in hospitalisation and cost for the health system. Improved diagnosis and management of COPD may reduce the incidence of hospitalisation and death among this population. This scoping review aims to identify improvement interventions designed to standardise the hospital care of patients with AECOPD at presentation, admission and discharge, and/or aim to reduce unnecessary admissions/readmissions. METHODS: The review followed a published protocol based on methodology set out by Arksey and O'Malley and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Electronic database searches for peer-reviewed primary evidence were conducted in Web of Science, EMBASE (Elsevier) and PubMed. Abstract, full-text screening and data extraction were completed independently by a panel of expert reviewers. Data on type of intervention, implementation supports and clinical outcomes were extracted. Findings were grouped by theme and are presented descriptively. RESULTS: 21 articles met the inclusion criteria. Eight implemented a clinical intervention bundle at admission and/or discharge; six used a multidisciplinary care pathway; five used coordinated case management and two ran a health coaching intervention with patients. CONCLUSION: The findings indicate that when executed reliably, improvement initiatives are associated with positive outcomes, such as reduction in length of stay, readmissions or use of health resources. Most of the studies reported an improvement in staff compliance with the initiatives and in the patient's understanding of their disease. Implementation supports varied and included quality improvement methodology, multidisciplinary team engagement, staff education and development of written or in-person delivery of patient information. Consideration of the implementation strategy and methods of support will be necessary to enhance the likelihood of success in any future intervention.

Transcriptional control of central carbon metabolic flux in Bifidobacteria by two functionally similar, yet distinct LacI-type regulators.

Bifidobacteria resident in the gastrointestinal tract (GIT) are subject to constantly changing environmental conditions, which require rapid adjustments in gene expression. Here, we show that two predicted LacI-type transcription factors (TFs), designated AraQ and MalR1, are involved in regulating the central, carbohydrate-associated metabolic pathway (the so-called phosphoketolase pathway or bifid shunt) of the gut commensal Bifidobacterium breve UCC2003. These TFs appear to not only control transcription of genes involved in the bifid shunt and each other, but also seem to commonly and directly affect transcription of other TF-encoding genes, as well as genes related to uptake and metabolism of various carbohydrates. This complex and interactive network of AraQ/MalR1-mediated gene regulation provides previously unknown insights into the governance of carbon metabolism in bifidobacteria.

Air Travel for Subjects Receiving Long-Term Oxygen Therapy.

BACKGROUND: Ambulatory oxygen (O2) is the recommended treatment for hypoxemia at rest or induced by exercise. Commercial aircraft often fly at altitudes of 30,000 feet; their cabins are pressurized to altitudes of 6,000-8,000 feet, with an equivalent FIO2 of 0.15. O2 supplementation, for those receiving baseline ambulatory O2, is paramount. METHODS: We gathered information on subjects' experience traveling with supplementary oxygen and reasons individuals receiving O2 do not travel. Subjects were identified using a home oxygen database. Data were gathered by postal questionnaire. The objective of this study was to gather information relevant to subjects' experience organizing travel with supplementary oxygen and their experience of traveling itself. RESULTS: Between 2013 and 2015, 512 patients were entered into the database: 277 were excluded (269 had died, 8 had incomplete records). We sent 235 questionnaires, and 50 responses were received (21% response rate). Of these, 11 (22%) were returned as the patient had died, 20 (40%) had not traveled by air, 11 (22%) had flown with O2, 4 (8%) no longer used O2, and 4 (8%) forms were incomplete. Of those who traveled with O2, 54% found it complicated to organize their trip, 72% found it complicated to access information, and 81% would fly again. Regarding those who had never flown with O2, 35% were unaware that O2 was available on commercial aircraft, 30% had no wish to travel, and 30% had worries regarding their health. CONCLUSIONS: Air travel is challenging; however, those who did travel reported a mainly positive experience. Increasing available information on options for travel should help individuals.

Glycoside hydrolase family 13 α-glucosidases encoded by Bifidobacterium breve UCC2003; A comparative analysis of function, structure and phylogeny.

Bifidobacterium breve is a noted inhabitant and one of the first colonizers of the human gastro intestinal tract (GIT). The ability of this bacterium to persist in the GIT is reflected by the abundance of carbohydrate-active enzymes that are encoded by its genome. One such family of enzymes is represented by the α-glucosidases, of which three, Agl1, Agl2 and MelD, have previously been identified and characterized in the prototype B. breve strain UCC2003. In this report, we describe an additional B. breve UCC2003-encoded α-glucosidase, along with a B. breve UCC2003-encoded α-glucosidase-like protein, designated here as Agl3 and Agl4, respectively, which together with the three previously described enzymes belong to glycoside hydrolase (GH) family 13. Agl3 was shown to exhibit hydrolytic specificity towards the α-(1→6) linkage present in palatinose; the α-(1→3) linkage present in turanose; the α-(1→4) linkages found in maltotriose and maltose; and to a lesser degree, the α-(1→2) linkage found in sucrose and kojibiose; and the α-(1→5) linkage found in leucrose. Surprisingly, based on the substrates analyzed, Agl4 did not exhibit biologically relevant α-glucosidic activity. With the presence of four functionally active GH13 α-glucosidases, B. breve UCC2003 is capable of hydrolyzing all α-glucosidic linkages that can be expected in glycan substrates in the lower GIT. This abundance of α-glucosidases provides B. breve UCC2003 with an adaptive ability and metabolic versatility befitting the transient nature of growth substrates in the GIT.

Defining exacerbations in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease is a very common disease often punctuated by intermittent episodes of exacerbation. These exacerbations affect the natural history of the disease, accelerating a decline in lung function. They affect the individual in many ways and affect the health service caring for these patients. The definition of exacerbation varies and lacks clarity. The definitions used most are either symptom based, for example, breathlessness, sputum production and sputum purulence, or event driven, for example, an event causing a patient to seek healthcare input or change to medications. In this article, we discuss the importance of exacerbations, the clinical definitions, clinical trial definitions, physiological and biomarker evidence of exacerbations and the challenges associated with each of these. Application of a practical definition would aid in our clinical management of patients with chronic obstructive pulmonary disease and facilitate developments in future therapeutic advances through clinical trials.

Protective role for club cell secretory protein-16 (CC16) in the development of COPD.

Club cell secretory protein-16 (CC16) is the major secreted product of airway club cells, but its role in the pathogenesis of chronic obstructive pulmonary disease (COPD) is unclear. We measured CC16 airway expression in humans with and without COPD and CC16 function in a cigarette smoke (CS)-induced COPD murine model. Airway CC16 expression was measured in COPD patients, smokers without COPD and non-smokers. We exposed wildtype (WT) and CC16(-/-)mice to CS or air for up to 6 months, and measured airway CC16 expression, pulmonary inflammation, alveolar septal cell apoptosis, airspace enlargement, airway mucin 5AC (MUC5AC) expression, small airway remodelling and pulmonary function. Smokers and COPD patients had reduced airway CC16 immunostaining that decreased with increasing COPD severity. Exposing mice to CS reduced airway CC16 expression. CC16(-/-) mice had greater CS-induced emphysema, airway remodelling, pulmonary inflammation, alveolar cell apoptosis, airway MUC5AC expression, and more compliant lungs than WT mice. These changes were associated with increased nuclear factor-κB (NF-κB) activation in CC16(-/-) lungs. CS-induced acute pulmonary changes were reversed by adenoviral-mediated over-expression of CC16. CC16 protects lungs from CS-induced injury by reducing lung NF-κB activation. CS-induced airway CC16 deficiency increases CS-induced pulmonary inflammation and injury and likely contributes to the pathogenesis of COPD.

Are respiratory specialist registrars trained to teach?

Respiratory SpRs are interested in medical education but rarely observed when teaching and receive little feedback http://ow.ly/Our0m.

A novel nonhuman primate model of cigarette smoke-induced airway disease.

Small animal models of chronic obstructive pulmonary disease (COPD) have several limitations for identifying new therapeutic targets and biomarkers for human COPD. These include a pulmonary anatomy that differs from humans, the limited airway pathologies and lymphoid aggregates that develop in smoke-exposed mice, and the challenges associated with serial biological sampling. Thus, we assessed the utility of cigarette smoke (CS)-exposed cynomolgus macaque as a nonhuman primate (NHP) large animal model of COPD. Twenty-eight NHPs were exposed to air or CS 5 days per week for up to 12 weeks. Bronchoalveolar lavage and pulmonary function tests were performed at intervals. After 12 weeks, we measured airway pathologies, pulmonary inflammation, and airspace enlargement. CS-exposed NHPs developed robust mucus metaplasia, submucosal gland hypertrophy and hyperplasia, airway inflammation, peribronchial fibrosis, and increases in bronchial lymphoid aggregates. Although CS-exposed NHPs did not develop emphysema over the study time, they exhibited pathologies that precede emphysema development, including increases in the following: i) matrix metalloproteinase-9 and proinflammatory mediator levels in bronchoalveolar lavage fluid, ii) lung parenchymal leukocyte counts and lymphoid aggregates, iii) lung oxidative stress levels, and iv) alveolar septal cell apoptosis. CS-exposed NHPs can be used as a model of airway disease occurring in COPD patients. Unlike rodents, NHPs can safely undergo longitudinal sampling, which could be useful for assessing novel biomarkers or therapeutics for COPD.

Umeclidinium bromide and vilanterol in combination for the treatment of chronic obstructive pulmonary disease.

Drugs from the two major classes of bronchodilator; umeclidinium, a long-acting muscarinic antagonist (LAMA), and vilanterol, a long-acting ß2 agonist (LABA), have been combined in a single inhaler device for once-daily use in chronic obstructive pulmonary disease (COPD). These drugs have been proven safe and well tolerated in patients with COPD and show an enhanced improvement in FEV1 when compared to either drug in isolation and when compared with an established LAMA drug. In this article, we discuss the data supporting this combination inhaler and also review alternative combined LAMA/LABA options. We discuss where these agents are likely to find a place in the current therapy of COPD and where the future is likely to lead with these and other therapies.

Rapid lung function decline in smokers is a risk factor for COPD and is attenuated by angiotensin-converting enzyme inhibitor use.

OBJECTIVE: Cigarette smoking is the most important risk factor for COPD in the United States. Host factors that influence the rapid rate of FEV1 decline in smokers and how decline rate influences risk for developing COPD are unknown. The aim of this study was to characterize the rate of FEV1 decline in ever smokers, compare the risk of incident COPD between those with rapid decline and others, and determine the effect of selected drugs on rapid decline. METHODS: A total of 1,170 eligible ever smokers from the longitudinal Lovelace Smokers Cohort with repeat spirometry tests over a minimum follow-up period of 3 years (mean follow-up, 5.9 years) were examined, including 809 ever smokers without a spirometric abnormality at baseline. Longitudinal absolute decline in postbronchodilator FEV1 from the slope of the spirometric values over all examinations was annualized and classified as rapid (≥30 mL/y), normal (0-29.9 mL/y), or no (>0 mL/y) decline. Logistic regression and Kaplan-Meier survival curves were used for the analysis. RESULTS: Approximately 32% of ever smokers exhibited rapid decline. Among ever smokers without a baseline spirometric abnormality, rapid decline was associated with an increased risk for incident COPD (OR, 1.88; P=.003). The use of angiotensin-converting enzyme (ACE) inhibitors at baseline examination was protective against rapid decline, particularly among those with comorbid cardiovascular disease, hypertension, or diabetes (ORs 0.48, 0.48, and 0.12, respectively; P≤.02 for all analyses). CONCLUSIONS: Ever smokers with a rapid decline in FEV1 are at higher risk for COPD. Use of ACE inhibitors by smokers may protect against this rapid decline and the progression to COPD.

Muscle weakness predicts pharyngeal dysfunction and symptomatic aspiration in long-term ventilated patients.

BACKGROUND: Prolonged mechanical ventilation is associated with muscle weakness, pharyngeal dysfunction, and symptomatic aspiration. The authors hypothesized that muscle strength measurements can be used to predict pharyngeal dysfunction (endoscopic evaluation-primary hypothesis), as well as symptomatic aspiration occurring during a 3-month follow-up period. METHODS: Thirty long-term ventilated patients admitted in two intensive care units at Massachusetts General Hospital were included. The authors conducted a fiberoptic endoscopic evaluation of swallowing and measured muscle strength using medical research council score within 24 h of each fiberoptic endoscopic evaluation of swallowing. A medical research council score less than 48 was considered clinically meaningful muscle weakness. A retrospective chart review was conducted to identify symptomatic aspiration events. RESULTS: Muscle weakness predicted pharyngeal dysfunction, defined as either valleculae and pyriform sinus residue scale of more than 1, or penetration aspiration scale of more than 1. Area under the curve of the receiver-operating curves for muscle strength (medical research council score) to predict pharyngeal, valleculae, and pyriform sinus residue scale of more than 1, penetration aspiration scale of more than 1, and symptomatic aspiration were 0.77 (95% CI, 0.63-0.97; P = 0.012), 0.79 (95% CI, 0.56-1; P = 0.02), and 0.74 (95% CI, 0.56-0.93; P = 0.02), respectively. Seventy percent of patients with muscle weakness showed symptomatic aspiration events. Muscle weakness was associated with an almost 10-fold increase in the symptomatic aspiration risk (odds ratio = 9.8; 95% CI, 1.6-60; P = 0.009). CONCLUSION: In critically ill patients, muscle weakness is an independent predictor of pharyngeal dysfunction and symptomatic aspiration. Manual muscle strength testing may help identify patients at risk of symptomatic aspiration.

The role of systemic inflammatory biomarkers to predict mortality in chronic obstructive pulmonary disease.

The authors discuss the role of inflammatory biomarkers to predict mortality in chronic obstructive pulmonary disease (COPD) in this narrative literature review with expert opinion. The severity of COPD has traditionally been graded using the degree of obstruction as measured by the forced expiratory volume in 1 s because this variable has been predictive of outcomes. However, it is now accepted that COPD is a complex disease with important systemic consequences and that a multidimensional index such as the BMI, obstruction, dyspnea and exercise capacity index is a better predictor of outcome than lung function alone. Because inflammation is thought to play a pivotal role in the genesis of COPD, several serum inflammatory biomarkers have been investigated. Of the ones studied, C-reactive protein, IL-6, pulmonary and activation-regulated chemokine and fibronectin:C-reactive protein ratio have been observed to be independently associated with increased risk of death. When added to known clinical variables such as the BMI, obstruction, dyspnea and exercise capacity index, only IL-6 has been shown to further contribute to mortality prediction. It is likely that the use of an integrative approach combining biomarkers investigated through high-output technology with clinical parameters, combined with new information from the fields of genomics, transcriptomics, proteomics and metabolomics, will improve the authors capacity to predict mortality in COPD.

A novel survey tool to assess pulmonary and critical care fellows' attitudes regarding acquiring teaching skills during fellowship training.

BACKGROUND: Important components of fellowship training include learning teaching skills and career development. Pulmonary and critical care medicine (PCCM) fellows' opinions of the importance of developing teaching skills and interest in careers in medical education have not been previously described, and there are no tools to assess interest in acquiring teaching skills. OBJECTIVE: We describe the development and initial psychometric validation of a survey tool to assess trainees' attitudes toward and interest in acquiring teaching skills. METHODS: A survey tool to assess attitudes toward teaching and medical education skills was designed and psychometrically characterized. We then anonymously surveyed fellows in 1 PCCM program to assess their perceptions of and attitudes regarding acquiring teaching skills. RESULTS: The survey tool demonstrated acceptable psychometric properties. The survey showed that most fellows felt that acquiring teaching skills was "very important," and nearly half reported being "interested" or "very interested" in pursuing careers as medical educators. However, fellows disagreed with the feedback they received from attending physicians with regard to their teaching abilities (10% disagreed with feedback at the beginning of the year, 36% disagreed at the end of the year; P  =  .03). CONCLUSIONS: Our survey demonstrates acceptable psychometric properties and performance characteristics in a single-site study of PCCM fellows during 1 academic year. Fellows are interested in improving their teaching skills but do not know how to become better teachers. Added research in multiple settings should explore the generalizability of our findings.

Comparison of arterial and venous blood biomarker levels in chronic obstructive pulmonary disease.

PURPOSE: The development of novel biomarkers is an unmet need in chronic obstructive pulmonary disease (COPD). Arterial blood comes directly from the lung and venous blood drains capillary beds of the organ or tissue supplied. We hypothesized that there would be a difference in levels of the biomarkers metalloproteinase 9 (MMP-9), vascular endothelial growth factor A (VEGF-A) and interleukin 6 (IL-6) in arterial compared with venous blood.  METHODS: Radial artery and brachial vein blood samples were taken simultaneously in each of 12 patients with COPD and seven controls with normal lung function. Circulating immunoreactive MMP-9, VEGF-A and IL-6 levels in serum were measured using quantitative enzyme-linked immunosorbent assays. RESULTS were compared using a Student's paired t test. The study was powered to determine whether significant differences in cytokine levels were present between paired arterial and venous blood samples.   RESULTS: In the 12 patients with COPD, four were female, and age ranged 53-85 years, mean age 69 years. Three patients in the control group were female, with age range 46-84 years, mean age 64.7 years. In the COPD group, three patients had mild, five moderate and four severe COPD. No significant difference was found between arterial and venous levels of MMP-9, VEGF-A or IL-6.  CONCLUSIONS: In this pilot study, levels of the measured biomarkers in arterial compared with venous blood in both COPD patients and healthy controls did not differ. This suggests that as we continue to chase the elusive biomarker in COPD as a potential tool to measure disease activity, we should focus on venous blood for this purpose.

Pulmonary zygomycosis in a non-neutropenic patient with myelodysplastic syndrome on lenalidomide.

Pulmonary zygomycosis is an uncommon infection that occurs mostly in immunocompromised patients. We report the case of a 75-year-old man with myelodysplastic syndrome, treated with lenalidomide for 3 months, who developed respiratory failure and a rapidly progressive left upper lobe consolidation. An extensive workup was unrevealing of the etiology, and the patient expired. A full autopsy was declined, but an in situ post-mortem transbronchial lung biopsy revealed pulmonary zygomycosis. This unique case illustrates the potential risks of lenalidomide therapy in patients with myelodysplastic syndrome and the difficulties in diagnosing pulmonary zygomycosis. To our knowledge this is the first report of a diagnostic in situ post-mortem transbronchial lung biopsy.

Acupuncture as an adjunct to pulmonary rehabilitation.

PURPOSE: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation and by both systemic and airway inflammation. In COPD, acupuncture has been shown to improve quality-of-life scores and decrease breathlessness; similar findings have also been reported after pulmonary rehabilitation (PR). The hypothesis of this study was that acupuncture in conjunction with pulmonary rehabilitation would improve COPD outcome measures compared to pulmonary rehabilitation alone. METHODS: The design was a randomized prospective study; all subjects had COPD. There were 19 controls, 25 who underwent PR, and 16 who had both acupuncture and PR. The primary outcome measure was a change in measures of systemic inflammation at the end of PR and at 3 month followup. Lung function, including maximum inspiratory pressure (PiMax), quality-of-life scores, functional capacity including steps taken, dyspnea scores, and exercise capacity, were secondary endpoints. RESULTS: After PR, both groups had significantly improved quality-of-life scores, reduced dyspnea scores, improved exercise capacity, and PiMax, but no change in measures of systemic inflammation compared with the controls. There were no differences in most of the outcome measures between the 2 treatment groups except that subjects who had both acupuncture and PR remained less breathless for a longer period. CONCLUSION: The addition of acupuncture to PR did not add significant benefit in most of the outcomes measured.

Chemotherapy-associated recurrent pneumothoraces in lymphangioleiomyomatosis.

Lymphangioleiomyomatosis is a rare cause of pneumothorax in women. We present the case of a 48-year-old woman with lymphangioleiomyomatosis, who had never had a pneumothorax prior to commencing chemotherapy for breast cancer. During chemotherapy she developed 3 pneumothoraces and 2 episodes of pneumomediastinum. We suggest that the pneumothoraces were caused by the chemotherapy. To our knowledge, this is the first reported case of chemotherapy triggering pneumothoraces in a woman with lymphangioleiomyomatosis.