Sex Differences in COVID-19 Hospitalization and Hospital Mortality among Patients with COPD in Spain: A Retrospective Cohort Study

(1) Background: We aimed to assess the effect of COPD in the incidence of hospital admissions for COVID-19 and on the in-hospital mortality (IHM) according to sex. (2) Methods: We used national hospital discharge data to select persons aged ≥40 years admitted to a hospital with a diagnosis of COVID-19 in 2020 in Spain. (3) Results: The study population included 218,301 patients. Age-adjusted incidence rates of COVID-19 hospitalizations for men with and without COPD were 10.66 and 9.27 per 1000 persons, respectively (IRR 1.14; 95% CI 1.08–1.20; p < 0.001). The IHM was higher in men than in women regardless of the history of COPD. The COPD was associated with higher IHM among women (OR 1.09; 95% CI 1.01–1.22) but not among men. The COPD men had a 25% higher risk of dying in the hospital with COVID-19 than women with COPD (OR 1.25, 95% CI 1.1–1.42). (4) Conclusions: Sex differences seem to exist in the effect of COPD among patients suffering COVID-19. The history of COPD increased the risk of hospitalization among men but not among women, and COPD was only identified as a risk factor for IHM among women. In any case, we observed that COPD men had a higher mortality than COPD women. Understanding the mechanisms underlying these sex differences could help predict the patient outcomes and inform clinical decision making to facilitate early treatment and disposition decisions.     

Association of Inhaled Corticosteroids With All-Cause Mortality Risk in Patients With COPD: A Meta-analysis of 60 Randomized Controlled Trials

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Association of Inhaled Corticosteroids with Incident Pneumonia and Mortality in COPD Patients; Systematic Review and Meta-Analysis

Background: Inhaled corticosteroids are commonly prescribed for patients with severe COPD. They have been associated with increased risk of pneumonia but not with increased pneumonia-associated or overall mortality. Methods: To further examine the effects of inhaled corticosteroids on pneumonia incidence, and mortality in COPD patients, we searched for potentially relevant articles in PubMed, Medline, CENTRAL, EMBASE, Scopus, Web of Science and manufacturers' web clinical trial registries from 1994 to February 4, 2014. Additionally, we checked the included and excluded studies' bibliographies. We subsequently performed systematic review and meta-analysis of included randomized controlled trials and observational studies on the topic. Results: We identified 38 studies: 29 randomized controlled trials and nine observational studies. The estimated unadjusted risk of pneumonia was increased in randomized trials: RR 1.61; 95% CI 1.35–1.93, p < 0.001; as well as in observational studies: OR 1.89; 95% CI 1.39–2.58, p < 0·001. Six randomized trials and seven observational studies were useful in estimating unadjusted risk of pneumonia ­case-fatality: RR 0.91; 95% CI 0.52–1.59, p = 0.74; and OR 0.72; 95% CI 0.59–0.88, p = 0.001, respectively. Twenty-nine randomized trials and six observational studies allowed estimation of unadjusted risk of overall mortality: RR 0.95; 95% CI 0.85–1.05, p = 0.31; and OR 0.79; 95% CI 0.65–0.97, p = 0.02, respectively. Conclusions: Despite a substantial and significant increase in unadjusted risk of pneumonia associated with inhaled corticosteroid use, pneumonia fatality and overall mortality were found not to be increased in randomized controlled trials and were decreased in observational studies.     

Risk of Pneumonia with Different Inhaled Corticosteroids in COPD Patients: A Meta-Analysis

Abstract

ICS are anti-inflammatory agents which have been suggested to benefit people with worsening symptoms of COPD, by improving lung function, reducing exacerbation of disease, and enhancing overall quality of life. This systematic review and meta-analysis explored the association of the risk of pneumonia in COPD patients that were undergoing treatment using ICS alone or together with LABAs or LAMAs. PubMed, Cochrane Library and EMBASE were systematically searched through August 1, 2019; only double-blinded randomized controlled trials were eligible for this study. Eighteen randomized controlled trials were included. ICS treatment was linked to increased pneumonia incidence (RR, 1.47; 95% CI, 1.26–1.71; p?<?0.001; I2?=?39.6%). Patients treated with salmeterol/fluticasone were more likely to have experience pneumonia-related adverse events than those treated using budesonide/formoterol or beclomethasone/formoterol. In subgroup analyses, pneumonia risk was found to be higher in the subgroups: >65?years old, lowest baseline forced expiratory volume in the first second of expiration (FEV1) < 50% of the predicted value, highest ICS dose, and long duration of ICS use. Furthermore, we compared fluticasone propionate with fluticasone furoate and determined that pneumonia incidence was higher in the former group and pneumonia incidence rose as doses rose in these two groups. However, no difference was observed between the budesonide and beclomethasone groups. ICS treatment was linked to an elevated pneumonia risk, different kinds of ICS lead to different rates of pneumonia.     

Association of Comorbidities With Postoperative In-Hospital Mortality: A Retrospective Cohort Study

The purpose of this article is to evaluate the American Society of Anesthesiologists Physical Status (ASA PS) and the Charlson comorbidity index (CCI) for the prediction of postoperative mortality.The ASA PS has been suggested to be equally good as the CCI in predicting postoperative outcome. However, these scores have never been compared in a broad surgical population.We conducted a retrospective cohort study in a German tertiary care university hospital. Predictive accuracy was compared using the area under the receiver-operating characteristic curves (AUROC). In a post hoc approach, a regression model was fitted and cross-validated to estimate the association of comorbidities and intraoperative factors with mortality. This model was used to improve prediction by recalibrating the CCI for surgical patients (sCCIs) and constructing a new surgical mortality score (SMS).The data of 182,886 patients with surgical interventions were analyzed. The CCI was superior to the ASA PS in predicting postoperative mortality (AUROC_CCI 0.865 vs AUROC_ASAPS 0.833, P < 0.001). Predictive quality further improved after recalibration of the sCCI and construction of the new SMS (AUROC_SMS 0.928 vs AUROC_sCCI 0.896, P < 0.001). The SMS predicted postoperative mortality especially well in patients never admitted to an intensive care unit.The newly constructed SMS provides a good estimate of patient''s risk of death after surgery. It is capable of identifying those patients at especially high risk and may help reduce postoperative mortality.     

Effects of Extra-Fine Inhaled and Oral Corticosteroids on Alveolar Nitric Oxide in COPD

Purpose

Alveolar nitric oxide (CA_NO) has been suggested as a surrogate marker of distal airway inflammation in COPD. Coarse particle-inhaled corticosteroids (ICS) have been shown not to suppress CA_NO. We evaluated whether extra-fine particle size ICS (HFA-BDP) or systemic oral corticosteroids could suppress CA_NO in COPD.

Methods

Chronic obstructive pulmonary disease (COPD) patients with a FEV1/FVC ratio <0.7, FEV1 <80% predicted with CA_NO?>?2?ppb underwent a double-blind randomized, controlled, crossover trial with an open-label systemic steroid comparator. After a 2?week steroid washout period, participants were randomized to 3?weeks of 100 mcg of HFA-BDP twice daily and then 3?weeks of 400?mcg of HFA-BDP twice daily, or matched placebos with subsequent crossover. All patients then received 1?week open-label, 25?mg/day of prednisolone. Exhaled nitric oxide, plasma cortisol, and lung function were recorded. CA_NO was corrected for axial diffusion.

Results

In 16 participants, there were no significant differences seen with either dose of HFA-BDP compared with placebo. Oral prednisolone significantly reduced FE_NO and J’aw_NO but not CA_NO. Plasma cortisol was significantly suppressed by oral prednisolone only.

Conclusions

Whilst CA_NO remains a biomarker of interest in COPD, it is not suppressed by systemic or extra-fine particle ICS. CA_NO is not a useful marker for monitoring response of small airway disease to therapies in COPD. The study was approved by the local Committee on Medical Research Ethics and registered on ClinicalTrials.Gov (NCT 00921921).     

Inhaled Corticosteroids Increase the Risk of Pneumonia in Patients With Chronic Obstructive Pulmonary Disease: A Nationwide Cohort Study

The association of inhaled corticosteroids (ICS) and pneumonia in patients with chronic obstructive pulmonary disease (COPD) is still controversial.From the National Health Insurance Database of Taiwan, COPD cases with history of acute exacerbation (AE) were identified (COPD cohort). Time-dependent Cox regression analysis was applied to investigate the risk factors for pneumonia with COPD severity controlled by surrogate variables. Among the COPD cohort, those who continuously used ICS for more than 360 days without interruption were selected (ICS cohort). The incidence rate of pneumonia during ICS use was compared with those before ICS use and after ICS discontinuation by using pair t test.A total of 6034 and 842 cases were identified as the COPD and ICS cohorts, respectively. In the COPD cohort, recent ICS use was independently associated with pneumonia (hazard ratio: 1.06 [1.02–1.11] for per 80 mg of budesonide). Other independent risk factors included age, male, diabetes mellitus, malignancy, low income, baseline pneumonia event, and recent use of oral corticosteroids and aminophylline. In the ICS cohort, while AE rate gradually decreased, the incidence rate of pneumonia significantly increased after ICS use (from 0.10 to 0.21 event/person-year, P = 0.001).This study demonstrates the association between ICS use and pneumonia in patients with COPD and history of AE. ICS should be judiciously used in indicated COPD patients.     

Presentation and Mortality of Cryptococcal Infection Varies by Predisposing Illness: A Retrospective Cohort Study

BackgroundCryptococcal epidemiology is changing in the modern antiretroviral era, and immune status informs outcomes. We describe the differences in clinical presentation and mortality of cryptococcosis by immune status in the antiretroviral therapy era.MethodsWe conducted a single-center retrospective cohort study of patients diagnosed with cryptococcosis from 2002 through 2017. Data included demographics, clinical features, diagnostics, and mortality.ResultsWe identified 304 patients with Cryptococcus neoformans infections: 105 (35%) were people living with human immunodeficiency virus (HIV), 41 (13%) had a history of transplantation, and 158 (52%) were non-HIV nontransplant (NHNT). Age analysis showed that people living with HIV were younger (40 years) than transplant (53 years) and NHNT (61 years) (P < .001). Fevers and headache were more common in people living with HIV (70% and 57%) than in transplant (49% and 29%) and NHNT (49% and 38%) (P = .003 and P = .001), respectively. Meningitis was more common in people living with HIV (68%) than in transplant recipients (32%) or NHNT (39%, P < .001). Disseminated cryptococcosis was more common in people living with HIV (97%) as compared with transplant (66%) or NHNT (73%) (P < .001). Time to diagnosis from hospitalization was longer for transplant (median 2 days, interquartile range [IQR] ± 9 days) and NHNT patients (median 2 days, IQR ± 7 days) as compared with people living with HIV (median 1 day, IQR ± 2 days) (P = .003). NHNT patients had a higher risk of 90-day mortality (hazard ratio 3.3; 95% confidence interval, 1.9-5.8) as compared with people living with HIV.ConclusionsThe majority of cryptococcosis occurs in NHNT patients. NHNT patients had more localized pulmonary cryptococcosis and significantly higher 90-day mortality. Cryptococcosis in NHNT patients appears to be a distinct entity that needs further study and requires a higher level of clinical suspicion than it currently receives.     

A Controlled Trial of Inhaled Bronchodilators in Familial Dysautonomia

Background

Chronic lung disease is a leading cause of premature death in patients with familial dysautonomia (FD). A significant number of patients have obstructive airway disease, yet it is not known whether this is pharmacologically reversible.

Methods

We conducted a double-blind, placebo-controlled, randomized clinical trial comparing the beta 2 agonist albuterol with the muscarinic blocker ipratropium bromide in patients homozygous for the IKBKAP founder mutation. Albuterol, ipratropium bromide, and placebo were administered on 3 separate days via nebulizer in the seated position. Airway responsiveness was evaluated using spirometry and impulse oscillometry 30 min post dose. Cardiovascular effects were evaluated by continuous monitoring of blood pressure, RR intervals, cardiac output, and systemic vascular resistance.

Results

A total of 14 patients completed the trial. Neither active agent had significant detrimental effects on heart rate or rhythm or blood pressure. Albuterol and ipratropium were similar in their bronchodilator effectiveness causing significant improvement in forced expiratory volume in 1-s (FEV1, p?=?0.002 and p?=?0.030). Impulse oscillometry measures were consistent with a reduction in total airway resistance post nebulization (resistance at 5 Hz p?<?0.006).

Conclusion

Airway obstruction is pharmacologically reversible in a number of patients with FD. In the short term, both albuterol and ipratropium were well tolerated and not associated with major cardiovascular adverse events.

     

Bronchodilators in COPD: Impact of ��-agonists and anticholinergics on severe exacerbations and mortality

This review summarizes the long-term clinical outcomes associated with β-agonist and anticholinergic bronchodilator use in patients with chronic obstructive pulmonary disease (COPD). Pooled data from randomized placebo-controlled trials of at least three months duration were used to evaluate the risk for COPD hospitalizations, respiratory mortality, and total mortality. The results show that anticholinergic use is associated with a 30% reduction in COPD hospitalizations, a 70% reduction in respiratory mortality, and without a significant effect on total mortality. In contrast, β-agonist use had no effect on COPD hospitalizations and was associated with a two-fold increased risk for respiratory death compared with placebo. When the two bronchodilators were directly compared with each other, β-agonists were associated with a two-fold increased risk for COPD hospitalization and a five-fold increased risk for total mortality compared with anticholinergics. When β-agonists were added to either anticholinergic use or inhaled corticosteroid use alone, there was no significant improvement in any long-term clinical outcome. These results indicate that anticholinergics should be the bronchodilator of choice in COPD, while β-agonists may be associated with poorer disease control.     

Clinical Impact of Portal Vein Thrombosis Prior to Liver Transplantation: A Retrospective Cohort Study

Introduction. To identify the impact of portal vein thrombosis (PVT) and associated medical and surgical factors on outcomes post liver transplant (LT).Material and methods. Two analyses were performed. Analysis One: cohort study of 505 consecutive patients who underwent LT (Alberta) between 01/2002-12/2012. PVT was identified in 61 (14%) patients. Analysis Two: cohort study of 144 consecutive PVT patients from two sites (Alberta and London) during the same period. Cox multivariable survival analysis was used to identify independent associations with post-LT mortality.Results. In Analysis One (Alberta), PVT was not associated with post-LT mortality (log rank p = 0.99). On adjusted analysis, complete/occlusive PVT was associated with increased mortality (Hazard Ratio (HR) 8.4, p < 0.001). In Analysis Two (Alberta and London), complete/occlusive PVT was associated with increased mortality only on unadjusted analysis (HR 3.7, p = 0.02). On adjusted analysis, Hepatitis C (HR 2.1, p = 0.03) and post-LT portal vein re-occlusion (HR 3.2, p = 0.01) were independently associated with increased mortality.Conclusion: Well-selected LT patients who had PVT prior to LT had similar post-LT outcomes to non-PVT LT recipients. Subgroups of PVT patients who did worse post-LT (complete/occlusive thrombosis pre-LT, Hepatitis C or post-LT portal vein re-occlusion) warrant closer evaluation in listing and management post-LT.     

Impact of Preoperative Testing on Patients Undergoing Ophthalmologic Surgery: A Retrospective Cohort Study

Objective: Routine medical testing is not recommended before cataract surgery, but no consensus exists about preoperative testing before general ophthalmologic surgery. We aimed to assess the impact of preoperative testing on patients undergoing ophthalmologic surgery by analyzing their surgical outcomes and complications.Methods: We retrospectively reviewed electronic health records of patients who had preoperative evaluations before cataract or noncataract ophthalmologic surgery at a tertiary care center from January 1, 2015, through December 31, 2019.Results: The cohort consisted of 2268 patients (1270 [56.0%] women). The most frequent ophthalmologic procedure was cataract extraction (n = 1450 [63.9%]). Laboratory tests results were available for 489 patients (33.7%) in the cataract group; of these, 275 results (56.2%) had abnormal values, and 18 patients (6.5%) required preoperative interventions. Preoperative test results were available for 772 out of 818 patients (94.4%) having noncataract procedures. Of these, 384 results (49.7%) had abnormal values, and 10 patients (2.6%) required additional intervention. No significant differences were observed for the rate of surgery cancellations between the cataract and noncataract patient groups (0.6% vs 1.0%; P = .24). Of the 12 patients (0.5%) who had complications, all had undergone preoperative testing.Conclusions: No differences in outcomes and complications were observed among patients who underwent cataract or noncataract surgery. It is reasonable to consider avoiding preoperative testing in patients undergoing ophthalmologic surgery.     

The Risk of Sepsis with Inhaled and Oral Corticosteroids in Patients with COPD

The use of oral and inhaled corticosteroids is associated with increases in the risk of infection, especially pneumonia. The risk of sepsis with corticosteroid treatment in patients with chronic obstructive pulmonary disease (COPD) has been little studied, however. We assessed whether the use of inhaled and oral corticosteroids in COPD is associated with an increase in the risk of sepsis. We carried out a retrospective cohort study using the administrative health databases of the province of Quebec, Canada, over the period 1990–2007. The cohort of patients with COPD included patients aged 55 years or older who used respiratory medications. A quasi-cohort analysis was used to estimate the rate ratio (RR) of sepsis in current users of inhaled corticosteroids and oral corticosteroids separately, after adjusting for differences in COPD disease severity and co-morbid conditions. The cohort included 163,514 patients treated for COPD, including 1,704 who were hospitalized for or died with sepsis during follow-up (incidence rate 1.94 per 1000 per year). The RR of sepsis associated with current use of inhaled corticosteroids was 0.98 (95%confidence interval [CI] 0.84–1.14). Current oral corticosteroid use was associated with a 66% increase in the risk of sepsis (RR 1.66; 95% CI: 1.35–2.05). The increase in risk remains for around 5 months after the oral corticosteroid exposure. Among patients treated for COPD, the risk of sepsis is not increased with inhaled corticosteroids, even at high doses, while the risk is increased with oral corticosteroids. This risk should be considered when treating exacerbations of COPD.