Search

Background The risk of severe COVID-19 varies significantly among persons of similar age and is higher in males. Age-independent, sex-biased differences in susceptibility to severe COVID-19 may be ascribable to deficits in a sexually dimorphic protective attribute that we termed immunologic resilience (IR). Objective To examine whether deficits in IR that antedate or are induced by SARS-CoV-2 infection independently predict COVID-19 mortality. Methods IR levels were quantified with two novel metrics: immune health grades (IHG-I [best] to IHG-IV) to gauge CD8+ and CD4+ T-cell count equilibrium, and blood gene expression signatures. IR metrics were examined in a prospective COVID-19 cohort (n=522); primary outcome was 30-day mortality. Associations of IR metrics with outcomes in non-COVID-19 cohorts (n=13,461) provided the framework for linking pre-COVID-19 IR status to IR during COVID-19, as well as to clinical outcomes. Results IHG-I, tracking high-grade equilibrium between CD8+ and CD4+ T-cell counts, was the most common grade (73%) among healthy adults, particularly in females. SARS-CoV-2 infection associated with underrepresentation of IHG-I (21%) vs. overrepresentation (77%) of IHG-II or IHG-IV, especially in males vs. females (P Conclusion Preservation of immunocompetence with controlled inflammation during antigenic challenges is a hallmark of IR and associates with longevity and AIDS resistance. Independent of age, a male-biased proclivity to degrade IR before and/or during SARS-CoV-2 infection predisposes to severe COVID-19. Clinical implications Biomarkers tracking immunologic resilience may have broad prognostic utility, as they associated with longevity, as well as resistance to a progressive disease course during SARS-CoV-2, influenza, or HIV infection.

Over the last few years, there has been a renewed interest in patients with characteristics of both asthma and COPD. Although the precise definition of asthma-COPD overlap (ACO) is still controversial, patients with overlapping features are frequently encountered in clinical practice, and may indeed have worse clinical outcomes and increased health-care utilization than those with asthma or COPD. Therefore, there is a critical need to set a framework for the therapeutic approach of such patients. There are key distinctions in the therapy between asthma and COPD, particularly regarding the initial choice of therapy. However, there is considerable overlap in the use of existing medications for both diseases. Furthermore, novel therapies approved for asthma, such as monoclonal antibodies, may have a role in patients with COPD and ACO. The use of biomarkers, such as peripheral blood eosinophils, exhaled nitric oxide, and serum IgE, may help in selecting appropriate therapies for ACO. In this review, we provide an overview of available treatments for both asthma and COPD and explore their potential role in the treatment of patients with ACO.

Contains fulltext : 220761.pdf (Publisher’s version ) (Open Access) Rationale: The decades-long progression of chronic obstructive pulmonary disease (COPD) renders identifying different trajectories of disease progression challenging.Objectives: To identify subtypes of patients with COPD with distinct longitudinal progression patterns using a novel machine-learning tool called "Subtype and Stage Inference" (SuStaIn) and to evaluate the utility of SuStaIn for patient stratification in COPD.Methods: We applied SuStaIn to cross-sectional computed tomography imaging markers in 3,698 Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1-4 patients and 3,479 controls from the COPDGene (COPD Genetic Epidemiology) study to identify subtypes of patients with COPD. We confirmed the identified subtypes and progression patterns using ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) data. We assessed the utility of SuStaIn for patient stratification by comparing SuStaIn subtypes and stages at baseline with longitudinal follow-up data.Measurements and Main Results: We identified two trajectories of disease progression in COPD: a "Tissue-->Airway" subtype (n = 2,354, 70.4%), in which small airway dysfunction and emphysema precede large airway wall abnormalities, and an "Airway-->Tissue" subtype (n = 988, 29.6%), in which large airway wall abnormalities precede emphysema and small airway dysfunction. Subtypes were reproducible in ECLIPSE. Baseline stage in both subtypes correlated with future FEV1/FVC decline (r = -0.16 [P < 0.001] in the Tissue-->Airway group; r = -0.14 [P = 0.011] in the Airway-->Tissue group). SuStaIn placed 30% of smokers with normal lung function at elevated stages, suggesting imaging changes consistent with early COPD. Individuals with early changes were 2.5 times more likely to meet COPD diagnostic criteria at follow-up.Conclusions: We demonstrate two distinct patterns of disease progression in COPD using SuStaIn, likely representing different endotypes. One third of healthy smokers have detectable imaging changes, suggesting a new biomarker of "early COPD."

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a chronic respiratory condition characterised by persistent respiratory symptoms and airflow limitation. Acute exacerbations punctuate the natural history of COPD and are associated with increased morbidity and mortality and disease progression. Chronic airflow limitation is caused by a combination of small airways (bronchitis) and parenchymal destruction (emphysema), which can impact day‐to‐day activities and overall quality of life. In carefully selected patients with COPD, long‐term, prophylactic use of antibiotics may reduce bacterial load, inflammation of the airways, and the frequency of exacerbations. OBJECTIVES: To assess effects of different prophylactic antibiotics on exacerbations, quality of life, and serious adverse events in people with COPD in three separate network meta‐analyses (NMAs), and to provide rankings of identified antibiotics. SEARCH METHODS: To identify eligible randomised controlled trials (RCTs), we searched the Cochrane Airways Group Specialised Register of trials and clinical trials registries. We conducted the most recent search on 22 January 2020. SELECTION CRITERIA: We included RCTs with a parallel design of at least 12 weeks' duration evaluating long‐term administration of antibiotics prophylactically compared with other antibiotics, or placebo, for patients with COPD. DATA COLLECTION AND ANALYSIS: This Cochrane Review collected and updated pair‐wise data from two previous Cochrane Reviews. Searches were updated and additional studies included. We conducted three separate network meta‐analyses (NMAs) within a Bayesian framework to assess three outcomes: exacerbations, quality of life, and serious adverse events. For quality of life, we collected data from St George's Respiratory Questionnaire (SGRQ). Using previously validated methods, we selected the simplest model that could adequately fit the data for every analysis. We used threshold analysis to indicate which results were robust to potential biases, taking into account each study’s contributions to the overall results and network structure. Probability ranking was performed for each antibiotic class for exacerbations, quality of life, and serious adverse events. MAIN RESULTS: Characteristics of studies and participants Eight trials were conducted at multiple sites that included hospital clinics or academic health centres. Seven were single‐centre trials conducted in hospital clinics. Two trials did not report settings. Trials durations ranged from 12 to 52 weeks. Most participants had moderate to severe disease. Mean age ranged from 64 years to 73 years, and more males were recruited (51% to 100%). Forced expiratory volume in one second (FEV₁) ranged from 0.935 to 1.36 L. Most participants had previous exacerbations. Data from 12 studies were included in the NMAs (3405 participants; 16 treatment arms including placebo). Prophylactic antibiotics evaluated were macrolides (azithromycin and erythromycin), tetracyclines (doxycyclines), quinolones (moxifloxacin) and macrolides plus tetracyclines (roxithromycin plus doxycycline). Risk of bias and threshold analysis Most studies were at low risk across domains, except detection bias, for which only seven studies were judged at low risk. In the threshold analysis for exacerbations, all comparisons in which one antibiotic was compared with another were robust to sampling variation, especially macrolide comparisons. Comparisons of classes with placebo were sensitive to potential bias, especially macrolide versus placebo, therefore, any bias in the comparison was likely to favour the active class, so any adjustment would bring the estimated relative effect closer to the null value, thus quinolone may become the best class to prevent exacerbations. Exacerbations Nine studies were included (2732 participants) in this NMA (exacerbations analysed as time to first exacerbation or people with one or more exacerbations). Macrolides and quinolones reduced exacerbations. Macrolides had a greater effect in reducing exacerbations compared with placebo (macrolides: hazard ratio (HR) 0.67, 95% credible interval (CrI) 0.60 to 0.75; quinolones: HR 0.89, 95% CrI 0.75 to 1.04), resulting in 127 fewer people per 1000 experiencing exacerbations on macrolides. The difference in exacerbations between tetracyclines and placebo was uncertain (HR 1.29, 95% CrI 0.66 to 2.41). Macrolides ranked first (95% CrI first to second), with quinolones ranked second (95% CrI second to third). Tetracyclines ranked fourth, which was lower than placebo (ranked third). Contributing studies were considered as low risk of bias in a threshold analysis. Quality of life (SGRQ) Seven studies were included (2237 participants) in this NMA. SGRQ scores improved with macrolide treatment compared with placebo (fixed effect‐fixed class effect: mean difference (MD) ‐2.30, 95% CrI ‐3.61 to ‐0.99), but the mean difference did not reach the minimally clinical important difference (MCID) of 4 points. Tetracyclines and quinolones did not improve quality of life any more than placebo, and we did not detect a difference between antibiotic classes. Serious adverse events Nine studies were included (3180 participants) in the NMA. Macrolides reduced the odds of a serious adverse event compared with placebo (fixed effect‐fixed class effect: odds ratio (OR) 0.76, 95% CrI 0.62 to 0.93). There was probably little to no difference in the effect of quinolone compared with placebo or tetracycline plus macrolide compared with placebo. There was probably little to no difference in serious adverse events between quinolones or tetracycline plus macrolide. With macrolide treatment 49 fewer people per 1000 experienced a serious adverse event compared with those given placebo. Macrolides ranked first, followed by quinolones. Tetracycline did not rank better than placebo. Drug resistance Ten studies reported drug resistance. Results were not combined due to variation in outcome measures. All studies concluded that prophylactic antibiotic administration was associated with the development of antimicrobial resistance. AUTHORS' CONCLUSIONS: This NMA evaluated the safety and efficacy of different antibiotics used prophylactically for COPD patients. Compared to placebo, prolonged administration of macrolides (ranked first) appeared beneficial in prolonging the time to next exacerbation, improving quality of life, and reducing serious adverse events. No clear benefits were associated with use of quinolones or tetracyclines. In addition, antibiotic resistance was a concern and could not be thoroughly assessed in this review. Given the trade‐off between effectiveness, safety, and risk of antibiotic resistance, prophylactic administration of antibiotics may be best reserved for selected patients, such as those experiencing frequent exacerbations. However, none of the eligible studies excluded patients with previously isolated non‐tuberculous mycobacteria, which would contraindicate prophylactic administration of antibiotics, due to the risk of developing resistant non‐tuberculous mycobacteria.

Purpose The purpose of the study is to evaluate the frequency and barriers to use of ultrasound guidance for central venous catheter (CVC) insertion by physicians specializing in critical care and hospital medicine. Materials and methods A national cross-sectional electronic survey of intensivists and hospitalists was administered from November 2014 to January 2015. Results The survey response rate was 5.9% (1013/17 233). Moderate to very frequent use of ultrasound guidance varied by site: internal jugular vein (80%), subclavian vein (31%), and femoral vein (45%). Nearly all physicians (99%) who insert internal jugular CVCs daily use ultrasound guidance, whereas only 46% of physicians who insert subclavian CVCs daily use ultrasound guidance. Use of real-time ultrasound guidance varied by insertion site: internal jugular vein (73%), subclavian vein (28%), and femoral vein (42%). Most physicians (59%) reported not being comfortable with real-time needle tracking at the subclavian site. The most frequently reported barriers to use of ultrasound guidance were (1) limited availability of ultrasound equipment (28%), (2) perception of increased total procedure time (22%), and (3) concern for loss of landmark skills (13%). Conclusions Most intensivists routinely use ultrasound guidance to insert internal jugular CVCs but not subclavian CVCs. The most commonly reported barrier to ultrasound use was limited access to an ultrasound machine.

Objective: To describe the clinical features, proportion of lipid-laden alveolar macrophages in bronchoalveolar lavage (BAL), and short-term and 6-month to 12-month outcomes of patients with Electronic cigarette/Vaping product use-Associated Lung Injury (EVALI).Methods: Retrospective review of clinical characteristics, radiographs, and BAL samples for all patients with a history of vaping who presented with acute hypoxemic respiratory failure to the University Hospital in San Antonio, Texas from 9/2019 to 6/2020 was performed.Results: We report 16 cases (15 men; median age, 30 years [range 19-75]) of EVALI with a history of vaping Tetrahydrocannabinol (THC), nicotine, or both. The most common presenting symptoms were tachycardia, dyspnea, cough, and fever. All patients required supplemental oxygen, including two who required noninvasive positive pressure ventilation, and five who required mechanical ventilation. All 16 patients had bilateral ground-glass opacities (GGO) with peripheral sparing on chest computerizedtomography (CT). Cultures were negative, except for one patient who tested positive for rhinovirus. COVID-19 PCR was done in one individual which was negative. Cytology demonstrated lipid-laden macrophages on Oil-Red-O stain on fresh (i.e., without fixative) BAL in the majority of patients (N = 12) with a mean lipid-saturation percentage of 78% [range, 44%-100%] and the mean Colombo count of 194 [range, 101-359]. Fifteen patients were treated with systemic corticosteroids. The median length of hospital stay was 10 days. At discharge, three patients required supplemental oxygen. Eight of those who had follow-up imaging showed resolution of GGO. One patient had a relapse of symptoms and was again treated with systemic corticosteroids and mycophenolate, with resolution of symptoms. Fourteen patients who were evaluated after discharge denied vaping post-discharge (two patients were not able to be contacted and did not keep follow-up appointments).Conclusions: Successful diagnosis and management of EVALI requires a high clinical suspicion, thorough evaluation to rule out infectious etiologies, and aggressive treatment with systemic corticosteroids, along with sustained abstinence from vaping.

Background Asthma exacerbation risk increases with worsening asthma control. Prevailing numerical control tools evaluate only current symptom impairment despite the importance of also assessing risk based on exacerbation history. An easy-to-use questionnaire addressing impairment and risk domains of control is needed. Objective To validate a composite asthma control tool that includes impairment and risk assessments (Asthma Impairment and Risk Questionnaire [AIRQ]). Methods Four-hundred forty-two patients aged ≥12 years with physician-diagnosed asthma who were followed in specialty practices completed 15 impairment and risk questions with dichotomized yes/no responses. Patients spanned all Global Initiative for Asthma severities and were classified as well-controlled, not well-controlled, or very poorly controlled according to a standard of Asthma Control Test (ACT) score plus prior-year exacerbations. Logistic regression analyses identified questions with the greatest predictive validity to discriminate among patients and determine cut points for these 3 classifications. Results The final AIRQ comprises 10 equally weighted yes/no impairment and risk questions. The final 10-item models yielded receiver operating characteristic curves of 0.94 to identify well-controlled versus not well-/very poorly controlled and 0.93 to identify well-/not well-controlled versus very poorly controlled asthma, as reflected by the ACT plus prior-year exacerbations standard. Cut points of 0-1, 2-4, and 5-10 best represented well-, not well-, and very poorly controlled asthma. Conclusions AIRQ is a rigorously validated composite measure designed to identify adults and adolescents with varying degrees of asthma control. Ongoing investigations will determine test-retest reliability, responsiveness to change, and predictive ability for future exacerbations.

Background: Inhaled medications form the foundation of pharmacologic treatment for chronic obstructive pulmonary disease (COPD).The Delivery Makes a Difference (DMaD) project was conducted to better understand health care provider (HCP) and patient perspectives about the role of inhalation delivery devices in COPD, and to examine the nature of educational efforts between HCPs and patients on proper device technique. Methods: Data were derived from 2 original quantitative, web-based, descriptive, cross-sectional surveys distributed to HCPs who manage COPD (n=513) and patients with COPD (n=499) in the United States. Descriptive statistics were used to assess data across important demographic variables. Inferential statistics were used to assess differences in attitudinal, descriptive, and behavioral measures that were cross-tabulated with demographic data. Results: When prescribing medication for newly diagnosed patients with stable or unstable COPD, only 37% of HCPs considered type of device to be highly important, with only 45% of HCPs assessing device technique in every newly diagnosed patient. Patients with COPD were also relatively unconcerned with proper device technique (64% never concerned), regardless of their COPD severity. Although patients did not identify education as a significant impediment to proper device use, they reported inconsistent educational experiences. Conclusions: We found that HCPs and patients prioritize medication over device when selecting treatments, showing limited concerns about proper device use. These results highlight the need to coordinate professional education with patient-directed educational efforts to further promote proper device selection and use in COPD management.

Chronic asthma accounts for a significant amount of unscheduled office and emergency department (ED) visits. According to the latest World Health Organization statistics, asthma worldwide affects 300 million individuals and creates a substantial health burden by restricting the patient’s lifetime activities. Data estimate that asthma causes a loss of disability-adjusted life years over 150,000/year [1]. While most individuals with asthma can be controlled with current therapies, 5-10% of patients have difficult-to-control/refractory asthma. Severe or refractory asthma places a significant burden on the patient and often requires treatment with systemic glucocorticoids, which have significant side effects. The American Thoracic Society and the European Respiratory Society define refractory asthma as asthma that requires treatment with high-dose inhaled corticosteroids (ICS) plus a second controller and/or systemic corticosteroids to prevent it from becoming ‘‘uncontrolled’’ or asthma that remains ‘‘uncontrolled’’ despite this aggressive therapy. To fully meet this definition the diagnosis of asthma needs to be confirmed and comorbidities addressed as well. The above are considered major criteria for severe asthma and only one needs to be present for considering the diagnosis of refractory asthma [2]. For these reasons, clinicians must learn to identify and formulate additional diagnoses of “asthma imitators” [3]. One of the more common disorders associated with difficult-to-control asthma is vocal cord dysfunction (VCD) [4]. This disorder is known by many names, but current nomenclature endorsed by European and American societies correctly refers it as “Inducible Laryngeal Obstruction” (ILO) [5]. The following case demonstrates the importance of recognizing the clinical and spirometric features of ILO when asthma remains “refractory” to multiple therapies.

RationaleThe demographic, physiological, and computed tomography (CT) features associated with pneumothorax in smokers with and without chronic obstructive pulmonary disease (COPD) are not clearly defined.ObjectivesWe evaluated the hypothesis that pneumothorax in smokers is associated with male sex, tall and thin stature, airflow obstruction, and increased total and subpleural emphysema.MethodsThe study included smokers with and without COPD from the COPDGene Study, with quantitative chest CT analysis. Pleural-based emphysema was assessed on the basis of local histogram measures of emphysema. Pneumothorax history was defined by subject self-report.Measurements and main resultsPneumothorax was reported in 286 (3.2%) of 9,062 participants. In all participants, risk of prior pneumothorax was significantly higher in men (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.08-2.22) and non-Hispanic white subjects (OR, 1.90; 95% CI, 1.34-2.69). Risk of prior pneumothorax was associated with increased percent CT emphysema in all participants and participants with COPD (OR, 1.04 for each 1% increase in emphysema; 95% CI, 1.03-1.06). Increased pleural-based emphysema was independently associated with risk of past pneumothorax in all participants (OR, 1.05 for each 1% increase; 95% CI, 1.01-1.10). In smokers with normal spirometry, risk of past pneumothorax was associated with non-Hispanic white race and lifetime smoking intensity (OR, 1.20 for every 10 pack-years; 95% CI, 1.09-1.33).ConclusionsAmong smokers, pneumothorax is associated with male sex, non-Hispanic white race, and increased percentage of total and subpleural CT emphysema. Pneumothorax was not independently associated with height or lung function, even in participants with COPD. Clinical trial registered with www.clinicaltrials.gov (NCT00608764).

BACKGROUND The risk factors for acute episodes of respiratory disease in current and former smokers who do not have COPD are unknown. METHODS Eight thousand two hundred forty-six non-Hispanic white and black current and former smokers in the Genetic Epidemiology of COPD (COPDGene) cohort had longitudinal follow-up (LFU) every 6 months to determine acute respiratory episodes requiring antibiotics or systemic corticosteroids, an ED visit, or hospitalization. Negative binomial regression was used to determine the factors associated with acute respiratory episodes. A Cox proportional hazards model was used to determine adjusted hazard ratios (HRs) for time to first episode and an acute episode of respiratory disease risk score. RESULTS At enrollment, 4,442 subjects did not have COPD, 658 had mild COPD, and 3,146 had moderate or worse COPD. Nine thousand three hundred three acute episodes of respiratory disease and 2,707 hospitalizations were reported in LFU (3,044 acute episodes of respiratory disease and 827 hospitalizations in those without COPD). Major predictors included acute episodes of respiratory disease in year prior to enrollment (HR, 1.20; 95% CI, 1.15-1.24 per exacerbation), airflow obstruction (HR, 0.94; 95% CI, 0.91-0.96 per 10% change in % predicted FEV 1 ), and poor health-related quality of life (HR, 1.07; 95% CI, 1.06-1.08 for each 4-unit increase in St. George's Respiratory Questionnaire score). Risks were similar for those with and without COPD. CONCLUSIONS Although acute episode of respiratory disease rates are higher in subjects with COPD, risk factors are similar, and at a population level, there are more episodes in smokers without COPD.

Background Physical and psychological symptoms are the hallmark of patients’ subjective perception of their illness. The purpose of this analysis was to determine if patients with COPD have distinctive symptom profiles and to examine the association of symptom profiles with systemic biomarkers of inflammation. Methods We conducted latent class analyses of three physical (dyspnea, fatigue, and pain) and two psychological symptoms (depression and anxiety) in 302 patients with moderate to severe COPD using baseline data from a longitudinal observational study of depression in COPD. Systemic inflammatory markers included IL1, IL8, IL10, IL12, IL13, INF, GM-CSF, TNF-α (levels >75thcentile was considered high); and CRP (levels >3 mg/L was considered high). Multinominal logistic regression models were used to examine the association between symptom classes and inflammation while adjusting for key socio-demographic and disease characteristics. Results We found that a 4-class model best fit the data: 1) low physical and psychological symptoms (26%, Low-Phys/Low-Psych), 2) low physical but moderate psychological symptoms (18%, Low-Phys/Mod Psych), 3) high physical but moderate psychological symptoms (25%, High-Phys/Mod Psych), and 4) high physical and psychological symptoms (30%, High-Phys/High Psych). Unadjusted analyses showed associations between symptom class with high levels of IL7, IL-8 (p ≤ .10) and CRP (p

Neurocognitive impairment has been described in COPD patients, but little is known about its relationship with physical functioning and health-related quality of life (HRQL) in this chronically ill patient group.301 stable COPD patients completed the Trail Making Test (TMT-A: psychomotor speed and TMT-B: executive control); 198 patients completed the Memory Impairment Screen (MIS). Standardization of TMT-A and TMT-B scores to a normative population yielded classifications of normal, borderline, or impaired cognitive status. Using multivariable regression, we examined the relationship between the TMT-A, TMT-B, and MIS with physical functioning (physical activity, 6-min walk test, and grip strength) and health-related quality of life (HRQL) measured with the Chronic Respiratory Questionnaire and the SF-36.Nearly 30% of patients had either borderline or impaired cognition on the TMT-A or TMT-B. Adjusted models indicated that those with either borderline or impaired cognitive functioning had weaker grip strength (TMT-A borderline: β = -2.9, P 0.05; TMT-B borderline: β = -3.0, P 0.05; TMT-B impaired: β = -2.5, P 0.05) and lower scores on the mental health component summary score (MCS-SF-36 HRQOL) measure (TMT-A impaired: β = -4.7, P 0.01). No adjusted significant associations were found for other physical functioning measures or the other HRQL measures. Impaired memory showed a significant association only with the MCS scale.Cognitive function was not associated with most standard indicators of physical function or most measures of HRQL in COPD patients. Both TMT-A and TMT-B were associated with weaker grip strength, and the TMT-A and MIS with poorer mental health.

Asthma is an inflammatory lung condition that is the most common chronic disease affecting pregnancy. The changes in pulmonary physiology during pregnancy include increased minute ventilation, decreased functional residual capacity, increased mucus production, and airway mucosa hyperemia and edema. Pregnancy is also associated with a physiological suppression of the immune system. Many studies have described the heterogeneous immune system response in women with asthma during pregnancy, which partly explains why asthma has been shown to worsen, improve, or remain stable in equal proportions of women during pregnancy. Asthma may be associated with poor maternal and fetal outcomes. However, better maternal and fetal outcomes are observed with better asthma control. Asthma controller medications are generally thought to be safe during pregnancy, but limited data are available for some of the medicines. Newer medications like omalizumab open avenues for the treatment of asthma, but also pose a challenge, as there is limited experience with their use. Therefore, a multidisciplinary approach, including obstetricians, asthma specialists, and pediatricians should collaborate with the patient to carefully weigh the risks and benefits to determine an optimal management plan for each individual patient. The aim of this review article is to summarize the most recent literature about the immunological changes that occur during pregnancy, physiological and clinical implications of asthma on pregnancy, and asthma management and medication use in pregnant women.

To describe the development and implementation process and assess the effect on self-reported clinical practice changes of a multidisciplinary, collaborative, interactive continuing medical education (CME)/continuing education (CE) program on chronic obstructive pulmonary disease (COPD).Multidisciplinary subject matter experts and education specialists used a systematic instructional design approach and collaborated with the American College of Chest Physicians and American Academy of Nurse Practitioners to develop, deliver, and reproduce a 1-day interactive COPD CME/CE program for 351 primary care clinicians in 20 US cities from September 23, 2009, through November 13, 2010.We recorded responses to demographic, self-confidence, and knowledge/comprehension questions by using an audience response system. Before the program, 173 of 320 participants (54.1%) had never used the Global Initiative for Chronic Obstructive Lung Disease recommendations for COPD. After the program, clinician self-confidence improved in all areas measured. In addition, participant knowledge and comprehension significantly improved (mean score, 77.1%-94.7%; P.001). We implemented the commitment-to-change strategy in courses 6 through 20. A total of 271 of 313 participants (86.6%) completed 971 commitment-to-change statements, and 132 of 271 (48.7%) completed the follow-up survey. Of the follow-up survey respondents, 92 of 132 (69.7%) reported completely implementing at least one clinical practice change, and only 8 of 132 (6.1%) reported inability to make any clinical practice change after the program.A carefully designed, interactive, flexible, dynamic, and reproducible COPD CME/CE program tailored to clinicians' needs that involves diverse instructional strategies and media can have short-term and long-term improvements in clinician self-confidence, knowledge/comprehension, and clinical practice.

The value of quantitative CT (QCT) to identify chronic obstructive pulmonary disease (COPD) phenotypes is increasingly appreciated. The authors hypothesised that QCT-defined emphysema and airway abnormalities relate to St George's Respiratory Questionnaire (SGRQ) and Body-Mass Index, Airflow Obstruction, Dyspnea and Exercise Capacity Index (BODE).1200 COPDGene subjects meeting Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria for COPD with QCT analysis were included. Total lung emphysema was measured using the density mask technique with a -950 Hounsfield unit threshold. An automated programme measured mean wall thickness (WT), wall area percentage (WA%) and 10 mm lumenal perimeter (pi10) in six segmental bronchi. Separate multivariate analyses examined the relative influence of airway measures and emphysema on SGRQ and BODE.In separate models predicting SGRQ score, a 1 unit SD increase in each airway measure predicted higher SGRQ scores (for WT, 1.90 points higher, p=0.002; for WA%, 1.52 points higher, p=0.02; for pi10, 2.83 points higher p0.001). The comparable increase in SGRQ for a 1 unit SD increase in emphysema percentage in these models was relatively weaker, significant only in the pi10 model (for emphysema percentage, 1.45 points higher, p=0.01). In separate models predicting BODE, a 1 unit SD increase in each airway measure predicted higher BODE scores (for WT, 1.07-fold increase, p0.001; for WA%, 1.20-fold increase, p0.001; for pi10, 1.16-fold increase, p0.001). In these models, emphysema more strongly influenced BODE (range 1.24-1.26-fold increase, p0.001).Emphysema and airway disease both relate to clinically important parameters. The relative influence of airway disease is greater for SGRQ; the relative influence of emphysema is greater for BODE.

Background Cigarette smoking is a major risk factor for chronic obstructive pulmonary disease (COPD) and COPD severity. Previous genome-wide association studies (GWAS) have identified numerous single nucleotide polymorphisms (SNPs) associated with the number of cigarettes smoked per day (CPD) and a dopamine beta-hydroxylase (DBH) locus associated with smoking cessation in multiple populations. Objective To identify SNPs associated with lifetime average and current CPD, age at smoking initiation, and smoking cessation in patients with COPD. Methods GWAS were conducted in four independent cohorts encompassing 3441 ever-smoking patients with COPD (Global Initiative for Obstructive Lung Disease stage II or higher). Untyped SNPs were imputed using the HapMap (phase II) panel. Results from all cohorts were meta-analysed. Results Several SNPs near the HLA region on chromosome 6p21 and in an intergenic region on chromosome 2q21 showed associations with age at smoking initiation, both with the lowest p=2x10(-7). No SNPs were associated with lifetime average CPD, current CPD or smoking cessation with p

Summary Introduction Hispanics are the fastest growing ethnicity of the US population and the largest subset includes those of Mexican origin. Hispanics, including Mexican Americans (MAs), consistently report less tobacco exposure than European Americans (EAs), but limited data are available regarding differences in the clinical characteristics, severity of airflow obstruction, and functional status between MAs and EAs with chronic obstructive pulmonary disease (COPD). Methods Participants in a community-based study of aging and frailty among MAs and EAs, San Antonio Longitudinal Study of Aging, underwent spirometry. Participants with spirometry values consistent with COPD by Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria are described here. Results Thirty-four percent (248/721) of the participants who underwent spirometry had evidence of GOLD Stages 1–4 COPD. Significantly more MAs with COPD reported being never smokers compared to EAs with COPD. Among those with COPD who also smoked, MAs reported significantly less tobacco exposure than EAs (15.7 vs. 32.4 pack-years, respectively), but both groups had surprisingly similar severities of airflow obstruction. Additionally, MAs had worse functional status and perceived health than did EAs. Conclusions Despite significantly less exposure to tobacco smoke, MAs with COPD had a similar degree of obstruction to airflow compared with EAs with COPD. Healthcare providers should have a high index of suspicion for COPD in MAs who are exposed to even small amounts of cigarette smoke.

Rationale: One of the limitations associated with lung transplantation is the lack of available organs. Objective: To determine whether a lung donor–management protocol could increase the number of lungs for transplantation without affecting the survival rates of the recipients. Methods: We implemented the San Antonio Lung Transplant protocol for managing potential lung donors according to modifications of standard criteria for donor selection and strategies for donor management. We then compared information gathered during a 4-yr period, during which the protocol was used with information gathered during a 4-yr period before protocol implementation. Primary outcome measures were the procurement rate of lungs and the 30-d and 1-yr survival rates of recipients. Main Results: We reviewed data from 711 potential lung donors. The mean rate of lung procurement was significantly higher (p 0.0001) during the protocol period (25.5%) than during the preprotocol period (11.5%), with an estimated risk ratio of 2.2 in favor of the protocol period. More patients received transplants during the protocol period (n 121) than during the pre-protocol period (n 53; p 0.0001). Of 98 actual lung donors during the protocol period, 53 (54%) had initially been considered poor donors; these donors provided 64 (53%) of the 121 lung transplants. The type of donor was not associated with significant differences in recipients’ 30-d and 1-yr survival rates or any clinical measures of adequate graft function. Conclusions: The protocol was associated with a significant increase in the number of lung donors and transplant procedures without compromising pulmonary function, length of stay, or survival of the recipients.

Smoking cessation is the mainstay of recommended treatment for chronic obstructive pulmonary disease (COPD), yet many continue smoking. This study seeks to understand the characteristics of patients with COPD who have quit and those who have not quit to identify important factors to evaluate in smoking-cessation interventions.A cross-sectional survey of a random sample of 1.5 million, predominantly male Veterans Administration enrollees. Of the respondents (63% [n = 887,775]), those with at least 1 COPD visit, a smoking history, and aged more than 34 years were included in this analysis (n = 89 337). Differences in demographics, functional status, comorbidities, and provider-patient interactions were evaluated for current and former smokers.Ninety-seven percent of the cohort with COPD was male. Former smokers (n = 58 482) were older (mean age of 69.6 vs 62.8, P.001) and had more cardiac comorbidities, but better mental health (Mean Mental Component Summary score from the Veterans Short Form-36 +/- standard deviation of 43.4 +/- 13.2 vs 39.9 +/- 13.7, P.001) than current smokers (n = 25 595), respectively. In addition, former smokers more actively participated in their health care and had a better relationship with their provider than current smokers.Former smokers with COPD were older, had more cardiac comorbidities, better mental health, and better perceived provider-patient interactions than active smokers. This study highlights the importance of screening participants with COPD who are enrolling in forthcoming smoking cessation trials for mental illnesses. In addition, developing interventions that address psychiatric comorbidities and potentially improve provider-patient communication may be other key areas to evaluate in future smoking cessation trials in patients with COPD.

Chronic obstructive pulmonary disease (COPD) comprises a spectrum of conditions including chronic bronchitis, emphysema, asthma, and bronchiectasis. It has a prevalence in the United States of 5.1% to 5.4% in the middle-aged to elderly population, with a lower rate in nonsmoking individuals. Moreover, COPD is complicated by frequent and recurring acute exacerbations of chronic bronchitis (AECB). Overall, COPD represents the fourth leading cause of mortality in the United States and is the second leading cause of work disability. This condition is also associated with high morbidity and health care expenditures. Despite the controversy over the need to prescribe antibiotics for patients with AECB, high-risk patients have been identified who will benefit from this therapy.These include, patients with a history of repeated infections (>4 per year), comorbid illnesses (such as diabetes, asthma, coronary heart disease), or marked airway obstruction. Furthermore, a bacterial cause is shown in approximately 50% of AECB episodes, and primarily includes Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae. Additionally, resistance among community-acquired respiratory pathogens in the United States has risen dramatically, with beta-lactamase production evident in 40% of H. influenzae and greater than 95% of M. catarrhalis isolates, and with approximately 10% of pneumococci highly resistant to penicillin and simultaneously resistant to macrolide antibiotics. The criteria used to make choices for antibiotic use in patients with AECB should include knowledge of the frequencies of pathogen resistance and patients' clinical characteristics. An effective antibiotic, however, must be able to rapidly resolve the acute infection with the least patient morbidity and need for hospitalization. Although there remains controversy as to when to initiate antibiotic therapy in patients with AECB, several guidelines have been published.

COPD is a complex disease with exacerbations characterized by worsening of symptoms resulting in deteriorating lung function.To assess predictive factors of relapse for patients with acute exacerbations of COPD (AECB).Retrospective cohort analysis of visits for AECB.Veterans Affairs Medical Center.Three hundred sixty-two visits (173 patients) with documented COPD treated as outpatients for AECB.Severity of underlying COPD, severity of AECB, comorbid conditions, therapy, and relapse rates (return visit within 14 days with persistent or worsening symptoms).Each visit was analyzed individually (referred to as a patient-visit). One group received antibiotics (270 patient-visits), and the second group (92 patient-visits) did not. Both groups had similar demographics and severity of underlying COPD. The overall relapse rate was 22%. The majority of patient-visits (95%) with severe symptoms at presentation were prescribed antibiotics vs only 40% of those with mild symptoms. Twenty-nine of 92 patient-visits (32%) were followed by relapse in the group that was not given antibiotics, whereas only 50 of 270 (19%) treated with antibiotics relapsed (p0.001). Those treated with amoxicillin had an even higher relapse rate (20 of 37 patient-visits, or 54%) than those who did not receive antibiotics (p = 0.006).Relapse from AECB was not related to the severity of underlying disease or to the severity of the acute exacerbation. Patients treated with antibiotics had significantly lower relapse rates than those who did not receive antibiotics. However, the specific choice of antibiotic is important because those treated with amoxicillin had the highest relapse rates of all groups.

Physical activity (PA) has been found to be an excellent predictor of mortality beyond traditional measures in COPD. We aimed to determine the association between depression and anxiety with accelerometry-based PA in patients with COPD.We performed a cross-sectional analysis of baseline data from 148 stable patients with COPD enrolled in an ongoing, longitudinal, observational study. We measured PA (total daily step count) with a Stepwatch Activity Monitor over 7 days, depression and anxiety with the Hospital Anxiety and Depression Scales (HADSs), dyspnea with the Shortness of Breath Questionnaire, and functional capacity with the 6-min walk test.Increased anxiety was associated with higher levels of PA such that for every one-point increase in the HADS-Anxiety score there was a corresponding increase of 288 step counts per day (β=288 steps, P.001), after adjusting for all other variables. Higher levels of depressive symptoms were associated with lower PA (β=-176 steps, P=.02) only when anxiety was in the model. The interaction term for anxiety and depression approached significance (β=26, P=.10), suggesting that higher levels of anxiety mitigate the negative effects of depression on PA.The increased PA associated with anxiety in COPD is, to our knowledge, a novel finding. However, it is unclear whether anxious patients with COPD are more restless, and use increased psychomotor activity as a coping mechanism, or whether those with COPD who push themselves to be more physically active experience more anxiety symptoms. Future studies should evaluate for anxiety and PA to better inform how to improve clinical outcomes.Clinicaltrials.gov; No.: NCT01074515; URL: www.clinicaltrials.gov.

Background Improving a patient's ability to self-monitor and manage changes in chronic obstructive pulmonary disease (COPD) symptoms may improve outcomes. Objective To determine the efficacy of a comprehensive care management program (CCMP) in reducing the risk for COPD hospitalization. Design A randomized, controlled trial comparing CCMP with guideline-based usual care. (ClinicalTrials.gov registration number: NCT00395083) SETTING: 20 Veterans Affairs hospital-based outpatient clinics. Participants Patients hospitalized for COPD in the past year. Intervention The CCMP included COPD education during 4 individual sessions and 1 group session, an action plan for identification and treatment of exacerbations, and scheduled proactive telephone calls for case management. Patients in both the intervention and usual care groups received a COPD informational booklet; their primary care providers received a copy of COPD guidelines and were advised to manage their patients according to these guidelines. Patients were randomly assigned, stratifying by site based on random, permuted blocks of variable size. Measurements The primary outcome was time to first COPD hospitalization. Staff blinded to study group performed telephone-based assessment of COPD exacerbations and hospitalizations, and all hospitalizations were blindly adjudicated. Secondary outcomes included non-COPD health care use, all-cause mortality, health-related quality of life, patient satisfaction, disease knowledge, and self-efficacy. Results Of the eligible patients, 209 were randomly assigned to the intervention group and 217 to the usual care group. Citing serious safety concerns, the data monitoring committee terminated the intervention before the trial's planned completion after 426 (44%) of the planned total of 960 patients were enrolled. Mean follow-up was 250 days. When the study was stopped, the 1-year cumulative incidence of COPD-related hospitalization was 27% in the intervention group and 24% in the usual care group (hazard ratio, 1.13 [95% CI, 0.70 to 1.80]; P= 0.62). There were 28 deaths from all causes in the intervention group versus 10 in the usual care group (hazard ratio, 3.00 [CI, 1.46 to 6.17]; P= 0.003). Cause could be assigned in 27 (71%) deaths. Deaths due to COPD accounted for the largest difference: 10 in the intervention group versus 3 in the usual care group (hazard ratio, 3.60 [CI, 0.99 to 13.08]; P= 0.053). Limitations Available data could not fully explain the excess mortality in the intervention group. Ability to assess the quality of the educational sessions provided by the case managers was limited. Conclusion A CCMP in patients with severe COPD had not decreased COPD-related hospitalizations when the trial was stopped prematurely. The CCMP was associated with unanticipated excess mortality, results that differ markedly from similar previous trials. A data monitoring committee should be considered in the design of clinical trials involving behavioral interventions.

Air-fluid levels within emphysematous lung bullae are a relatively uncommon occurrence in patients with preexisting bullous disease, and are not commonly reported. We report 2 cases of new onset air-fluid levels in patients with underlying bullous disease with substantially different clinical presentations but with clinical improvement after medical therapy only.

COPD does not make exception to other chronic disease; it is essential to shift from an acute to a chronic care approach in managing the disease. A chronic care approach includes interactions between informed patients who actively participate in their care and experienced provider, resulting in higher quality and more cost-effective patient care environment. Self-management is a key component if we want the patient to have the control of his disease in a day-to-day basis. Case managers are used to empower patients and ensure that patients acquire the practical experience. Detailed information including patients’ workbooks and brochures, and health professionals’ teaching material and reference guides are provided on the website: www.livingwellwithCOPD.com (password: copd).

• The contemporary definition of an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is an event in the natural course of the disease characterized by a change in the patient’s baseline dyspnoea, cough, and/or sputum beyond the day-to-day variability sufficient to warrant a change in management. • Acute exacerbations of COPD are associated with enormous cost, increased rate of decline of lung function in continuous smokers, poor quality of life, and high mortality. • A trial of noninvasive mechanical ventilation (bi-level Positive Airway Pressure or bi-level PAP) should be attempted in patients with progressive respiratory acidosis, impending respiratory failure, or markedly increased work of breathing due to AECOPD because bi-level PAP is associated with success rates of 80–85% due to reduced intubation rates, lower rates of nosocomial infections, and improved mortality. • Aggressive prevention and management of AECOPD are important to help reduce the cost, morbidity, and mortality associated with these episodes.

Summary Introduction In chronic diseases such as chronic obstructive pulmonary disease (COPD), patients may not perceive all of the benefits of drug therapy until withdrawal. Thus, we evaluated the effect of tiotropium withdrawal on clinical variables. Methods COPD subjects who participated in two identical 1-year, prospective, double-blind, placebo-controlled studies of tiotropium 18μg once daily who completed a 3-week visit following discontinuation of therapy were included in this analysis. Outcomes measured included dyspnea (transition dyspnea index [TDI]), Peak Expiratory Flow Rate (PEFR), health status (St George's Respiratory Questionnaire [SGRQ]), and rescue β 2 -agonist use. Results Overall, the tiotropium group exhibited significant improvements in clinical parameters at the end of therapy. Of the entire cohort of 921 patients, 713 patients (77%) completed 3-weeks post-withdrawal evaluation. Patients in the tiotropium group had 1.1 unit worsening in TDI, decreased in PEFR, health status and reduced β 2 -agonist medication following treatment discontinuation, while the placebo group remained relatively stable. Conclusions The withdrawal of tiotropium results in worsening of COPD over a three-week interval. There was no evidence of a rebound effect in response to tiotropium withdrawal.

Background Implementation of the chronic care model (CCM) has been shown to be an effective preventative strategy to improve outcomes in diabetes mellitus, depression, and congestive heart failure, but data are lacking regarding the effectiveness of this model in preventing complications in patients with chronic obstructive pulmonary disease. Methods We searched the MEDLINE, CINAHL, and Cochrane databases from inception to August 2005 and included English-language articles that enrolled adults with chronic obstructive pulmonary disease and (1) contained intervention(s) with CCM component(s), (2) included a comparison group or measures at 2 points (before/after), and (3) had relevant outcomes. Two reviewers independently extracted data. Results Symptoms, quality of life, lung function, and functional status were not significantly different between the intervention and control groups. However, pooled relative risks (95% confidence intervals) for emergency/unscheduled visits and hospitalizations for the group that received at least 2 CCM components were 0.58 (0.42-0.79) and 0.78 (0.66-0.94), respectively. The weighted mean difference (95% confidence interval) for hospital stay was −2.51 (−3.40 to −1.61) days shorter for the group that received 2 or more components. There were no significant differences for those receiving only 1 CCM component. Conclusions Limited published data exist evaluating the efficacy of CCM components in chronic obstructive pulmonary disease management. However, pooled data demonstrated that patients with chronic obstructive pulmonary disease who received interventions with 2 or more CCM components had lower rates of hospitalizations and emergency/unscheduled visits and a shorter length of stay compared with control groups. The results of this review highlight the need for well-designed trials in this population.

The purpose of this study was to investigate the influence of hydroxypropyl methylcellulose (HPMC) molecular weight on pharmacokinetic and pharmacodynamic parameters of controlled release formulations containing alprazolam. Tablet formulations contained alprazolam, excipients, and either HPMC K4MP or HPMC K100LVP. A ten patient in vivo clinical trial using a randomized, open-label, four-way crossover design was conducted in the fed and fasted states. Plasma alprazolam concentrations were determined for 72 h. The pharmacodynamic effects of alprazolam were monitored using subject rated sedation on visual analogue scale for wakefulness, observer rated sedation, and symbol digit modalities test (SDMT). Results indicated that the tablet formulations containing either HPMC K4MP or HPMC K100LVP had similar dissolution profiles, and the dissolution profiles did not change through 6 months at 40 degrees C/75% RH or 12 months at 25 degrees C/65% Relative Humidity (RH). The area under the plasma concentration-time curve, time to peak concentration, and peak plasma concentration were not significantly different between the two tablet formulations investigated in either the fed or fasted states. Pharmacodynamically, no significant differences in SDMT scores between the two formulations were found. In vitro dissolution results predicted in vivo pharmacokinetic and pharmacodynamic results irrespective of formulation or diet used in the controlled release tablet. The controlled release tablets were bioequivalent and pharmacodynamically equivalent irrespective of the tablet formulation.

Antibiotics can be effective against acute exacerbations of chronic bronchitis and chronic obstructive pulmonary disease, but with bacterial resistance to multiple antibiotics increasing worldwide, appropriate antibiotic selection is critical. Categorizing patients with acute exacerbations according to age, number of exacerbations per year, disease severity, degree of pulmonary impairment, and presence of comorbid conditions helps to direct therapy.

Source Citation Llor C, Moragas A, Hernandez S, Bayona C, Miravitlles M. Efficacy of antibiotic therapy for acute exacerbations of mild to moderate chronic obstructive pulmonary disease. Am J Respi...