Background:The burden of frequent respiratory exacerbations in COPD patients with mild-to-moderate spirometric impairment and smokers with preserved lung function is unknown. Methods:We categorized COPD participants in COPDGene with post-bronchodilator FEV1%predicted≥50% by the annual exacerbation frequency into three groups: i)frequent exacerbators (top 5%; n = 109), ii)exacerbators (>0 but less than frequent exacerbators; n = 1,009), and iii)No exacerbation (n = 981). Exacerbations were defined as respiratory episodes requiring antibiotics and/or systemic steroids. We performed a Cox proportional hazards regression analysis to examine the association with mortality. We repeated the same process in current/former smokers with preserved spirometry (FEV1≥80%predicted and FEV1/FVC≥0.7). Results:Among 2,099 COPD participants, frequent exacerbators had ≥1.8 exacerbations/year and were responsible for 34.3% of the total exacerbations. There were 102 (10.4%) deaths in the group with no exacerbations, 119 (11.8%) in the exacerbator group, and 24 (22%) in the frequent exacerbators. Adjusted mortality in frequent exacerbators was higher relative to individuals with no exacerbations (hazard ratio (HR) = 1.98; 95%CI = 1.25-3.13). An increase in frequency of exacerbations by one exacerbation/year was associated with increased mortality (HR = 1.40,95%CI = 1.21-1.62). Among 3,143 participants with preserved spirometry, frequent exacerbators had ≥0.8 exacerbations/year and were responsible for more than half of the exacerbations. There were 93 (4.2%) deaths in the group with no exacerbations, 28 (3.8%) in the exacerbator group, and 14 (7.6%) in the frequent exacerbators. The adjusted mortality was increased in frequent exacerbators with preserved spirometry relative to those with no exacerbations (HR = 2.25; 95%CI = 1.26-4.01). Conclusions:In COPD participants with mild-to-moderate spirometric impairment and smokers with preserved spirometry, the frequent exacerbator phenotype is responsible for a large proportion of total exacerbations and associated with high mortality.
BackgroundNonadherence to treatment recommendation, common in patients with COPD and Asthma, leads to poor disease control, frequent exacerbations and emergency room visits. We studied the effect of a single home visit (HV) on adherence and health care utilization in a cohort of non-compliant Asthma and COPD patients.MethodsPatients with severe Asthma and COPD with frequent exacerbations deemed non-compliant were subjected to a single home visit by a multidisciplinary team. Adherence to inhalers and office visits, and healthcare utilization were assessed a year prior to and after the home visit.ResultsA total of 60 patients had an attempted home visit. Contact was made with 36 patients during the home visits and these were subject to analyses. Mean age was 60, and 61% were women. Average FEV1 was 1.56 L (55% predicted). There was a significant increase in compliance with office visits in the year following the HV as compared to the year before HV (87 vs 145 visits post-HV). Similarly, there was a significant reduction in the ER visits (76 visits vs 34 visits post-HV), and hospital admission (39 visits vs 24 post HV) and this was associated with a significant improvement in patient adherence to maintenance inhaler use - 17% (6 of 36) vs 53% (19 of 36).ConclusionIn patients with frequent exacerbations of Asthma and COPD with confirmed non-compliance, a single home visit by a multidisciplinary team improved patient adherence to inhalers and office visits and reduced healthcare utilization.
BackgroundDiagnosing and monitoring of children with respiratory disorders is often challenging. Respiratory sounds (RS) are simple, non-invasive and universally available measures that are directly related to movement of air, within the tracheobronchial tree. Thus, RS may be valuable indicators of respiratory health, their characteristics in the paediatric population are scattered in the literature and not systematized.AimSystematically review the different acoustic RS properties in healthy children and in children with different respiratory disorders. Methods: MEDLINE, EMBASE, AMED and CINHAL databases were searched on Sept 2020. One author extracted data and two independently assessed the quality of the articles using the National Heart Lung and Blood Institute quality assessment tool.ResultsTwenty-eight studies were included with a total 2032 participants (44% with a respiratory condition, such as asthma, bronchiolitis, cystic fibrosis, presence of wheezing and non-specified low respiratory tract infections). A high heterogeneity in the procedures, outcomes and outcome measures used was found. Healthy participants showed lower values of F50 (from 194 ± 26 to 521 ± 18Hz) than those with asthma (from 140 ± 8 to 769 ± 85Hz) or bronchiolitis (from 100 to 80Hz). F50 tend to increase with provocation tests (136 ± 9 to 909 ± 81Hz) and decrease with treatments (128 ± 6 to 781 ± 57Hz). Wheeze rates ranged from 0 to 24.7 ± 25% on asthmatic participants. Crackles findings ranged from 6% on people with recurrent wheezing to 30.8% in middle lobe atelectasis.ConclusionRS show different acoustic properties in healthy children vs with different respiratory disorders and thus may be useful in the diagnostic and monitoring on paediatrics.
•The main pathophysiological traits of COPD patients while exercising are the excess ventilation and dynamic hyperinflation.•In COPD patients, Sacin, a marker of small airway dysfunction, can predict excess ventilation and dynamic hyperinflation.•Small airways dysfunction crucially impacts on functional status of COPD patients.
As Covid-19 affects millions of people worldwide, the global health care will encounter an increasing burden of the aftermaths of the disease. Evidence shows that up to a fifth of the patients develop fibrotic tissue in the lung. The SARS outbreak in the early 2000 resulted in chronic pulmonary fibrosis in a subset (around 4%) of the patients, and correlated to reduced lung function and forced expiratory volume (FEV). The similarities between corona virus infections causing SARS and Covid-19 are striking, except that the novel coronavirus, SARS-CoV-2, has proven to have an even higher communicability. This would translate into a large number of patients seeking care for clinical signs of pulmonary fibrosis, given that the Covid-19 pandemic has up till now (Sept 2020) affected around 30 million people. The SARS-CoV-2 is dependent on binding to the angiotensin converting enzyme 2 (ACE2), which is part of the renin-angiotensin system (RAS). Downregulation of ACE2 upon virus binding disturbs downstream activities of RAS resulting in increased inflammation and development of fibrosis. The poor prognosis and risk of developing pulmonary fibrosis are therefore associated with the increased expression of ACE2 in risk groups, such as obesity, heart disorders and aging, conferring plenty of binding opportunity for the virus and subsequently the internalization of ACE2, thus devoiding the enzyme from acting counter-inflammatory and antifibrotic. Identifying pathways that are associated with Covid-19 severity that result in pulmonary fibrosis may enable early diagnosis and individualized treatment for these patients to prevent or reduce irreversible fibrotic damage to the lung.
Dual bronchodilator therapy with a long-acting muscarinic antagonist (LAMA) and a long-acting β2-agonist (LABA) is recommended in the pharmacological management of chronic obstructive pulmonary disease (COPD) according to the Global Initiative for Chronic Obstructive Lung Disease. To better understand the evidence supporting use of LAMA+LABA therapy in COPD and evaluate consistency within and across clinical research study types, we systematically reviewed and analyzed data from both randomized controlled trials (RCTs) and real-world studies. We searched PubMed from inception until April 4, 2019, for phase 2/3/4 RCTs of ≥24 weeks' duration and real-world studies in which the efficacy and/or safety of LAMA+LABAs were compared with monotherapies, other LAMA+LABAs, LABA+inhaled corticosteroid (ICS), or triple therapy (LAMA+LABA+ICS). We extracted primary and key secondary outcomes data from relevant articles for descriptive purposes. Overall, 24 RCTs and 8 real-world studies were included in the analysis based on predefined inclusion criteria. LAMA+LABAs improved lung function and health-related quality of life, and reduced exacerbation rates and dyspnea when compared with monotherapies, LABA+ICS, or triple therapy in both RCTs and real-world studies. Importantly, all LAMA+LABAs were well tolerated, with their safety profiles comparable to those of respective monotherapies, and had lower incidences of pneumonia than ICS-containing regimens. Results of RCTs and real-world studies are largely consistent; demonstrate that LAMA+LABAs improve lung function and health-related quality of life and reduce exacerbation rates and dyspnea relative to other available pharmacotherapies; and reinforce the position of LAMA+LABAs in the pharmacological management of COPD.
Right heart catheterization (RHC) is needed to diagnose pulmonary hypertension (PH). Traditional hemodynamic determinations may be insufficient to identify early stages of the disease and the mechanism of PH, confidently allocate patients to the pre- and/or postcapillary groups of the disease and guide certain treatment decisions (e.g. use of calcium channel blockers). In this review, we discuss the role of established (pulmonary vasodilatory, exercise and rapid fluid infusion challenges) and promising maneuvers (passive leg raising, intrathoracic pressure estimation, temporary exclusion of arteriovenous dialysis accesses and dobutamine infusion) that help interrogate the pulmonary vasculature during RHC, with a focus on describing rationale for use, indications, contraindications, protocols and implications of different responses.
•STOP-BANG rivals a comprehensive clinical evaluation as a screening tool for OSA.•STOP-BANG demonstrates 93% sensitivity for OSA and 97% sensitivity for moderate-to-severe OSA.•Combining the elements of all commonly used OSA screening instruments does not appreciably improve accuracy.
•Dupilumab improved lung function measures regardless of baseline biomarkers in OCS-dependent severe asthma patients.•Dupilumab showed steroid-sparing effects regardless of FEV1 improvement, and in exacerbation-free patients.•Patients with oral corticosteroid-dependent severe asthma appear to be highly skewed toward type 2 inflammation.
•The average annual disease-related costs for a COPD patient from a hospital register was twice as high as for a COPD case from a general population.•In a general population, moderate exacerbations fully explained all the costs of productivity losses for those with an FEV1 < 50% of predicted.•For the hospital sample, severe exacerbations explained a large part of the treatment-related costs, but not the costs of productivity losses.•Increasing severity of airflow obstruction was associated with increased costs in both samples.•Sampling source is of great importance when evaluating cost-of-illness studies of COPD.
•Six-minute walking test is the main predictor of mortality at diagnosis in IPF.•Six-minute walking test is cheap and easy to perform.•Total lung capacity could be another predictor of mortality.
In people hospitalised for an exacerbation of chronic obstructive pulmonary disease;•Exercise training initiated early during an admission was well tolerated.•Improvements were noted in exercise tolerance and muscle strength.•The exercise program increased the time spent walking at low intensity.
•Urinary fibrinopeptide A is increased in asthmatics 4.2 days prior to exacerbation.•Urinary fibrinopeptide A levels correlate negatively with plasma IgE.•Urinary fibrinopeptide A levels are associated with time to recovery.•Plasma D-dimer concentration increased significantly at exacerbation.•Plasma TGFβ concentration decreased significantly at exacerbation.
Background: Currently, five biologic treatment options are available for use in patients with uncontrolled persistent asthma: three interleukin (IL)-5 antagonists, which either bind to the anti-IL-5 ligand (mepolizumab, reslizumab) or to the IL-5 receptor (benralizumab); one anti-immunoglobulin E (anti-IgE) therapy (omalizumab); and one anti-IL-4/IL-13 therapy (dupilumab). To date, no comparative data from head-to-head clinical trials are available for these biologics. Objective: An indirect treatment comparison (ITC) of dupilumab versus each of the anti-IL-5 and anti-IgE therapies using the endpoints of annualized severe asthma exacerbation rates and change in pre-bronchodilator forced expiratory volume in 1 s (FEV1). Methods: Embase (R), MEDLINE (R), and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for studies published between January 1, 1980 and March 25, 2019. Eligible articles included randomized controlled trials (RCTs) in patients aged >= 12 years with persistent/uncontrolled asthma using at least medium-to-high dose inhaled corticosteroid plus long-acting beta(2)-agonist with add-on biologic therapy. Bucher ITCs were performed to compare subgroups of dupilumab patients with the anti-IL-5s and anti-IgE trial populations. Results: Fourteen RCTs were included in the analyses. The matched dupilumab subgroups were associated with greater reductions in annualized severe exacerbation rates compared with benralizumab, mepolizumab, reslizumab, and omalizumab (54%, 28%, 38%, and 26% greater reduction, respectively). A greater improvement in FEV1 was also observed for dupilumab at week 12 and/or week 24/52 than for the other biologics (0.06-0.14 L). Conclusion: In this ITC, dupilumab was associated with lower severe asthma exacerbation rates and greater improvements in lung function than anti-IL-5s and omalizumab.
•Higher blood and sputum eosinophil counts are associated with exacerbation's risk.•Blood and sputum eosinophils have similar predictive value for future exacerbations.•Prediction of exacerbation improved by combining inflammatory markers to lung function, ICS dose and exacerbations’ rate.•Sputum eosinophils >7.2% or blood eosinophils >360/mm3 predict the risk of exacerbation.
Idiopathic pulmonary fibrosis (IPF) is a devastating disease that kills as many Americans as breast cancer each year. This study investigated whether lung function decline and survival associates with adaptive immunity in patients with IPF, specifically the expression of checkpoint molecules ICOS, CD28 and PD-1 on circulating CD4 T cells. Clinical data, blood samples and pulmonary function tests were collected prospectively and longitudinally from 59 patients with IPF over a study period of 5 years. Patients were followed until death, lung transplantation, or study end, and cell surface expression of CD45RO, CD28, ICOS, and PD-1 was measured on CD4 T cells via flow cytometry. Repeated measures of ICOS and CD28 on CD4 T cells revealed significant associations between declining ICOS and CD28 expression, and declining lung function parameters FVC and DLCO, independent of age, sex, race, smoking history, or immunosuppressant use. Strikingly, patients in the highest quintile of ICOS at study entry had markedly improved survival, while those with low CD28 fared poorly. No change in PD-1 expression was found. Analysis of ICOS and CD28 from the first blood draw identified three populations of IPF patients; those at high risk for early death, those with intermediate risk, and those at low risk. These results highlight the role of T cell mediated immunity in IPF survival, finding the assessment of two T cell stimulatory checkpoint molecules, CD28 and ICOS, was sufficient to discriminate three distinct survival trajectories over 5 years of patient follow up.
Many patients with COPD are ventilatory limited and unable to tolerate effective levels of aerobic training. A scooter could be an enticing training modality if muscle activity is partitioned and distal leg muscle activity is emphasized. The aim of this study was to determine whether scooting might emphasize leg heaviness (desired muscle burden), relative to the breathing heaviness, when compared with walking. Participants completed two endurance tests, walking and scooting. The intensity for each targeted similar tolerable exercise times (tlimit) simulating comparable training session exposure. Participants scored (Borg0-10) leg and breathing heaviness throughout each test and the slope calculated. Electromyography was used to quantify leg muscle activity. 15 participants with COPD (mean[SD]: age = 64[11]y; FEV1 = 52[17]%predicted; FEV1/FVC = 50[10]%) completed the study. Successful matching of intensity between modalities was demonstrated by similar tlimit (difference [95%CI] = -0.3[-2.8 to 2.1]min). Scooting resulted in more (60[24 to 95]%) activity of the gastrocnemius in the propulsion and less (−82[-91 to −72]%) in the support leg. Rectus femoris activity was reduced (−68[-95 to −41]%) and increased (117[49 to 184]%) in the propulsion and support leg, respectively. There was no significant difference (0.1[-0.1 to 0.2]) in the relationship between breathing and leg heaviness when scooting was compared to walking. Scooting is associated with increased activity of the distal muscles of propulsion of the scooting leg. However, this is offset by the increased activity of the support leg as it resists the rotational force of propulsion, such that the relationship between breathing and leg heaviness is not altered.
•FF/UMEC/VI was predicted to reduce moderate/severe exacerbation rates vs BUD/FOR.•FF/UMEC/VI was predicted to improve quality-adjusted survival vs BUD/FOR.•FF/UMEC/VI was cost-effective vs BUD/FOR in UK NHS patients with symptomatic COPD.•In all scenario and sensitivity analyses, FF/UMEC/VI remained cost-effective.
The Publisher regrets that this article is an accidental duplication of an article that has already been published in < Respiratory Medicine: X 1C 100007>, http://dx.doi.org/<10.1016/j.yrmex.2019.100007>. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.
