Risk of cardiovascular events following COVID-19 in people with and without pre-existing chronic respiratory disease (preprint)

Background COVID-19 is associated with a higher risk of cardiovascular outcomes in the general population. People with chronic respiratory disease have a higher risk of cardiovascular disease than the general population therefore, we investigated the association between pre-existing chronic respiratory disease and risk of cardiovascular events following COVID-19 using routinely collected data from 56 million people in England. Methods Primary and secondary care data from the English National Health Service and COVID-19-specific linked data were used to define a population of adults with COVID-19 between 01/01/2020-30/11/2021. Start of follow-up was from first COVID-19 diagnosis. Pre-existing chronic respiratory disease included asthma, chronic obstructive pulmonary disease, bronchiectasis, cystic fibrosis, or pulmonary fibrosis prior to COVID-19 diagnosis. Adjusted Cox Proportional Hazard regression was used to investigate the association between pre-existing chronic respiratory disease and risk of cardiovascular events. Secondary objectives investigated the impact of COVID-19 hospitalisation and vaccine dose on risk of cardiovascular outcomes. Findings A total of 3,670,455 people were included. People with pre-existing respiratory disease had a higher risk of cardiovascular events (adjusted HR 1.11, 95% confidence intervals 1.07-1.14), heart failure (1.15, 1.09-1.21), and pulmonary embolism (1.20, 1.11-1.30) compared with those without pre-existing respiratory disease. Regardless of pre-existing respiratory disease, the risk of cardiovascular events was lower with increasing COVID-19 vaccine dose. Interpretation People with chronic respiratory disease have a higher risk of some cardiovascular outcomes but the risk might be explained by the underlying respiratory condition. Risk of cardiovascular events was lower with increasing COVID-19 vaccine doses regardless of pre-existing chronic respiratory disease. Funding This work was funded by the British Heart Foundation Data Science Centre.

[The impact of the COVID-19 epidemic on the course of the most common respiratory diseases]. / A COVID­19-járvány hatása a leggyakoribb légzoszervi megbetegedések lefolyására.

INTRODUCTION: SARS-CoV-2 has defined our everyday lives over the past three years and by constituting a serious risk factor for patients with pre-existing respiratory illnesses, it placed an unexpected burden on the health care systems worldwide. OBJECTIVE: The aim of this study was to explore the association between COVID-19 and pre-existing respiratory comorbidities such as chronic obstructive pulmonary disease (COPD) and asthma. METHOD: In our current study, we retrospectively processed the data of nearly 29 000 Hungarian patients. RESULTS: We found that COPD was directly associated with the severity of COVID-19 and slightly increased the risk of intensive care unit admission and the need for mechanical ventilation during the SARS-CoV-2 infection. On the other hand, the presence of asthma influenced neither the severity of COVID-19 nor the need for intensive care unit admission or mechanical ventilation significantly. DISCUSSION: International studies suggest that COPD does not significantly increase the risk of SARS-CoV-2 infection. However, the likelihood of hospitalization due to COVID-19 is much higher in COPD patients and the presence of COPD is associated with a more severe disease course. Given the structural alterations and abnormal regeneration processes of the airways that occur during lung injury in COPD patients, these individuals require increased attention and personalized rehabilitation protocols after the onset of the viral infection. CONCLUSION: Altogether, the assessment of clinical manifestations associated with different COPD phenotypes (as well as other chronic lung diseases) and SARS-CoV-2 infection is essential for the implementation of personalized therapeutic approach in the future. Orv Hetil. 2023; 164(2): 51-56.

Impact of accumulative smoking exposure and chronic obstructive pulmonary disease on COVID-19 outcomes: report based on findings from the Japan COVID-19 task force.

OBJECTIVES: Smoking and chronic obstructive pulmonary disease (COPD) are risk factors for severe COVID-19. However, limited literature exists on the effect of COPD and smoking on COVID-19 outcomes. This study examined the impact of smoking exposure in pack-years (PY) and COPD on COVID-19 outcomes among smokers in Japan. METHODS: The study included 1266 smokers enrolled by the Japan COVID-19 task force between February 2020 and December 2021. PY and COPD status was self-reported by patients. Patients were classified into the non-COPD (n = 1151) and COPD (n = 115) groups; the non-COPD group was further classified into <10 PY (n = 293), 10-30 PY (n = 497), and >30 PY (n = 361). The study outcome was the need for invasive mechanical ventilation (IMV). RESULTS: The incidence of IMV increased with increasing PY and was highest in the COPD group (<10 PY = 7.8%, 10-30 PY = 12.3%, >30 PY = 15.2%, COPD = 26.1%; P <0.001). A significant association was found for IMV requirement in the >30 PY and COPD groups through univariate (odds ratio [OR]: >30 PY = 2.11, COPD = 4.14) and multivariate (OR: >30 PY = 2.38; COPD = 7.94) analyses. Increasing PY number was also associated with increased IMV requirement in patients aged <65 years. CONCLUSION: Cumulative smoking exposure was positively associated with COVID-19 outcomes in smokers.

[Exacerbation of obstructive pulmonary diseases by SARS-CoV-2 infection in patients treated in the Pulmonology Clinic of Târgu Mures]. / Obstruktív tüdobetegségek súlyosbodása SARS-CoV-2-fertozés hatására a marosvásárhelyi Pulmonológiai Klinika beteganyagában.

INTRODUCTION: Literature data show an increased severity of SARS-CoV-2 infection in patients with cardiovascular, renal comorbidities, chronic obstructive pulmonary disease (COPD), asthma, obesity, diabetes, tumors and immunosuppression. METHOD: This retrospective study includes 90 patients with SARS-CoV-2 infection associated with COPD or asthma exacerbations from 303 patients hospitalized during a 7-month period (29.7%). The clinical aspect of COPD/asthma exacerbations overlapped to the one by SARS-CoV-2 infection, therefore, we compared our group with 90 patients with SARS-CoV-2 without obstructive disease. We excluded from both groups the patients with known severe cardiac impairment, diabetes, or tumors in order to not having interference with other unfavorable prognostic factors. We assessed the cases severity on clinical basis, pulzoximetry, CT/chest x-ray, and inflammatory markers. RESULTS: 72.2% of our group (48/52 with COPD and 17/38 with asthma) had moderate/severe pneumonia (bilateral interstitial-alveolar infiltrates, increased inflammatory markers, respiratory dysfunction) compared with 56.6% from the nonobstructive group. 14 patients required intensive therapy (including mechanical ventilation). We recorded 4 deaths in COPD group, 1 in asthma group, compared to 2 in non-obstructive patients (fatality 7.6% in COPD compared to 2.2% in nonobstructive group). Treatment included maximized inhaled bronchodilators ± corticosteroids, oxygen, antivirals, anticoagulants, corticosteroids, symptomatic. All patients were referred for clinical-functional and CT scan reassessment 2 months after discharge. CONCLUSION: The association of SARS-CoV-2 infection in patients with COPD or asthma was common, leading to exacerbation with significant severity. Fatality increased in COPD. Outpatient follow-up aims to restage adjust the treatment and monitor post-COVID-19 possible sequels. Orv Hetil. 2023; 164(2): 43-50.

Event Rate and Predictors of Post-Acute COVID-19 Sequalae and the Average Time to Diagnosis in General Population (preprint)

Background: Post-COVID-19 sequalae involves a variety of new, returning or ongoing symptoms that people experience more than four weeks after getting COVID-19. The aims of this meta-analysis were to assess the prevalence of Post-Acute COVID-19 sequalae and estimate the average time to its diagnosis; and meta-regress for possible moderators. Methods: A standard search strategy was used in PubMed, and then later modified according to each specific database. Search terms included; long COVID-19 or post-acute COVID-19 syndrome/sequalae. The criteria for inclusion were published clinical articles reporting the long COVID-19, further, the average time to diagnosis of post-acute COVID-19 sequelae among primary infected patients with COVID-19. Random-effects model was used. Rank Correlation and Eggers tests were used to ascertain publication bias. Sub-group, sensitivity and meta-regression analysis were conducted. A 95% confidence intervals were presented and a p-value < 0.05 was considered statistically significant. Review Manager 5.4 and comprehensive meta-analysis version 4 (CMA V4) were used for the analysis. The trial was PROSPERO registered (CRD42022328509). Results: Prevalence of post-acute COVID-19 sequalae was 42.5% (95% confidence interval (CI) 36 % to 49.3%). The PACS event rates range was 25 % at four months and 66 % at two months and mostly, signs and symptoms of PASC were experienced at three (54.3%, P < 0.0001) to six months (57%, P < 0.0001), further increasing at 12 months (57.9%, P= 0.0148). At an average of two months, however with the highest event rate (66%), it was not significantly associated with PACS diagnosis (P=0.08). On meta-regression, comorbidities collectively contributed to 14% of PACS with a non-significant correlation (Q = 7.05, df = 8, p = 0.5313) (R-squared analog = 0.14). A cardiovascular disorder especially hypertension as a stand-alone, showed an event rate of 32% and significantly associated with PACS, 0.322 (95% CI 0.166, 0.532) (P < 0.001). Chronic obstructive pulmonary disorder (COPD) and abnormal basal metabolic index (BMI) had higher event rates of PACS (59.8 % and 55.9 %) respectively, with a non-significant correlation (P > 0.05). With a significant association, hospital re-admission contributed to 17% (Q = 8.70, df = 1, p = 0.0032) (R-squared analog= 0.17) and the study design 26% (Q = 14.32, df = 3, p = 0.0025) (R-squared analog= 0.26). All the covariates explained at least some of the variance in effect size on PACS at 53% (Q = 38.81, df = 19, p = 0.0047) (R-squared analog = 0.53). Conclusion: The prevalence of PACS in general population was 42.5%, of which cardiovascular disorders were highly linked with it with COPD and abnormal BMI also being possible conditions found in patients with PACS. Hospital re-admission predicted highly, an experience of PACS as well as prospective study design. Clinical and methodological characteristics in a specific study contributed to over 50% of PACS events. The PACS event rates ranged between 25 % at four months and 66 % at two months with most signs and symptoms experienced between three to six months increasing at 12 months.

The Impact of COVID-19 on Cancer Screening and Treatment in Older Adults: The Multiethnic Cohort Study (preprint)

Background: The Coronavirus Disease of 2019 (COVID-19) has impacted the health and day-to-day life of individuals, especially the elderly and people with certain pre-existing medical conditions, including cancer. The purpose of this study was to investigate how COVID-19 impacted access to cancer screenings and treatment, by studying the participants in the Multiethnic Cohort (MEC) study. Methods: The MEC has been following over 215,000 residents of Hawai i and Los Angeles for the development of cancer and other chronic diseases since 1993-1996. It includes men and women of five racial and ethnic groups: African American, Japanese American, Latino, Native Hawaiian, and White. In 2020, surviving participants were sent an invitation to complete an online survey on the impact of COVID-19 on their daily life activities, including adherence to cancer screening and treatment. Approximately 7,000 MEC participants responded. A cross-sectional analysis was performed to investigate the relationships between the postponement of regular health care visits and cancer screening procedures or treatment with race and ethnicity, age, education, and comorbidity. Results: Women with more education, women with lung disease, COPD, or asthma, and women and men diagnosed with cancer in the past 5 years were more likely to postpone any cancer screening test/procedure due to the COVID-19 pandemic. Groups less likely to postpone cancer screening included older women compared to younger women and Japanese American men and women compared to White men and women. Conclusions: This study revealed specific associations of race/ethnicity, age, education level, and comorbidities with the cancer-related screening and healthcare of MEC participants during the COVID-19 pandemic. Increased monitoring of patients in high-risk groups for cancer and other diseases is of the utmost importance as the chance of undiagnosed cases or poor prognosis is increased as a result of delayed screening and treatment.Funding: This research was partially supported by the Omidyar 'Ohana Foundation and grant U01 CA164973 from the National Cancer Institute.

Characteristics of 12-Month Readmission for Hospitalized Patients with COPD: A Propensity Score Matched Analysis of Prospective Multicenter Study.

Purpose: Hospitalization for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is considered as severe exacerbations. Readmission for severe exacerbations is a crucial event for COPD patients. However, factors associated with readmission for severe exacerbations are incomplete. The study aimed to investigate different characteristics between the severe and non-severe exacerbation groups. Patients and Methods: Patients hospitalized for severe AECOPD were included in multi-centers, and their exacerbations in next 12 months after discharge were recorded. According to exacerbations, patients were separated into the severe-exacerbation group and the non-severe exacerbation group. Propensity-score matching (PSM) and multivariable analyses were performed to compare the baseline characteristics of two groups. The Hosmer-Lemeshow test and receiver operating characteristic curve were applied to evaluate how well the model could identify clusters. Results: The cohort included 550 patients with severe AECOPD across 27 study centers in China, and 465 patients were finally analyzed. A total of 41.5% of patients underwent readmission for AECOPD within 1 year. There were no significant differences in baseline characteristics between groups after PSM. Severe exacerbations in the 12 months were related to some factors, eg, the duration of COPD (13 vs 8 years, P<0.001), the COPD Assessment Test (CAT) score (20 vs 17, P<0.001), the blood eosinophil percentage (1.5 vs 2.0, P<0.05), and their inhaler therapies. Patients readmitted with AECOPD had a longer time of diagnosis (≥9 years), more symptoms (CAT ≥10), and lower blood eosinophils (Eos <2%). A clinical model was derived to help identify patients at risk of readmission with severe exacerbations. Conclusion: These analyses confirmed the relevance of COPD at admission with future severe exacerbations. A lower blood eosinophils percentage appears to be related to readmission when combined with clinical history. Further studies are needed to evaluate whether this study can predict the risk of exacerbations.

Qualitative Validation of COPD Evidenced Care Pathways in Japan, Canada, England, and Germany: Common Barriers to Optimal COPD Care.

Background: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. A comprehensive and detailed understanding of COPD care pathways from pre-diagnosis to acute care is required to understand the common barriers to optimal COPD care across diverse health systems. Methods: Country-specific COPD care pathways were created for four high-income countries using international recommendations and country-specific guidelines, then populated with published epidemiological, clinical, and economic data. To refine and validate the pathways, semi-structured interviews using pre-prepared discussion guides and country-specific pathway maps were held with twenty-four primary and secondary care respiratory healthcare professionals. Thematic analysis was then performed on the interview transcripts. Results: The COPD care pathway showed broad consistency across the countries. Three key themes relating to barriers in optimal COPD management were identified across the countries: journey to diagnosis, treatment, and the impact of COVID-19. Common barriers included presentation to healthcare with advanced COPD, low COPD consideration, and sub-optimal acute and chronic disease management. COVID-19 has negatively impacted disease management across the pathway but presents opportunities to retain virtual consultations. Structural factors such as insurance and short duration of appointments also impacted the diagnosis and management of COPD. Conclusion: COPD is an important public health issue that needs urgent prioritization. The use of Evidenced Care Pathways with decision-makers can facilitate evidence-based decision making on interventions and policies to improve care and outcomes for patients and reduce unnecessary resource use and associated costs for the healthcare provider/payer.

Expanding role of CXCR2 and therapeutic potential of CXCR2 antagonists in inflammatory diseases and cancers.

C-X-C motif chemokine receptor 2 (CXCR2) is G protein-coupled receptor (GPCR) and plays important roles in various inflammatory diseases and cancers, including chronic obstructive pulmonary disease (COPD), atherosclerosis, asthma, and pancreatic cancer. Upregulation of CXCR2 is closely associated with the migration of neutrophils and monocytes. To date, many small-molecule CXCR2 antagonists have entered clinical trials, showing favorable safety and therapeutic effects. Hence, we provide an overview containing the discovery history, protein structure, signaling pathways, biological functions, structure-activity relationships and clinical significance of CXCR2 antagonists in inflammatory diseases and cancers. According to the latest development and recent clinical progress of CXCR2 small molecule antagonists, we speculated that CXCR2 can be used as a biomarker and a new target for diabetes and that CXCR2 antagonists may also attenuate lung injury in coronavirus disease 2019 (COVID-19).

Clinical characteristics of severe coronavirus disease 2019 patients with chronic obstructive pulmonary disease. / é‡åž‹æ–°åž‹å† çŠ¶ç— æ¯’è‚ºç‚Žåˆå¹¶æ ¢æ€§é˜»å¡žæ€§è‚ºç–¾ç— æ‚£è€ ä¸´åºŠç‰¹å¾.

OBJECTIVES: Coronavirus disease 2019 (COVID-19) in elderly and patients with chronic respiratory diseases (COPD) had a poor prognosis. COPD is one of the most common chronic respiratory diseases. We explore the epidemiological characteristics of patients with severe COVID-19 with COPD patients in order to provide medical evidence for the prevention and treatment of severe COVID-19. METHODS: We retrospectively analyzed the clinical baseline characteristics, treatment strategies, disease progression and prognosis of 557 severe COVID-19 patients admitted to the West Court of Union Hospital of Huazhong University of Science and Technology from January 29, 2020 to April 8, 2020. RESULTS: A total of 465 patients with severe COVID-19 were enrolled in the study, including 248 (53.3%) males and 217 (46.7%) females. The median age of severe COVID-19 patients was 62.0 years, and 53 patients were complicated with COPD. Common symptoms at the onset included fever (78.5%), dry cough (67.1%), shortness of breath (47.3%) and fatigue (40.9%). Compared with non-COPD patients, patients with COPD had significantly lower levels of SpO2 in admission (90.0% vs 92.0%, P=0.014). In terms of laboratory examinations, patients with COPD had higher levels of C-reactive protein, interleukin-6, procalcitonin, total bilirubin, blood urea nitrogen, serum creatinine, lipoprotein (a), high-sensitivity troponin I, and D-dimer, while had lower levels of platelet counts, albumin and apolipoprotein AI. Severe COVID-19 patients with COPD had higher Sequential Organ Failure Assessment scores [3.0(2.0, 3.0) vs 2.0(2.0, 3.0), P=0.038] and CURB-65 score [1.0(1.0, 2.0) vs1.0(0.0, 1.0), P<0.001], and a higher proportion of progressing to critical illness (28.3% vs 10.0%, P<0.001) with more complications [e.g. septic shock (15.1% vs 6.1%, P=0.034)], had higher incidence rates of antibiotic therapies (90.6% vs 77.2%, P=0.025), non-invasive (11.3% vs 1.7%, P<0.001) and invasive mechanical ventilation (17.0% vs 8.3%, P=0.039), ICU admission (17.0% vs 7.5%, P=0.021) and death (15.1% vs 6.1%, P=0.016). Cox proportion hazard model was carried out, and the results showed that comorbid COPD was an independent risk factor for severe COVID-19 patients progressing to critical type, after adjusting for age and gender [adjusted hazard ratio (AHR)=2.38(1.30-4.37), P=0.005] and additionally adjusting for chronic kidney diseases, hypertension, coronary heart disease [AHR=2.63(1.45-4.77), P<0.001], or additionally adjusting for some statistically significant laboratory findings [AHR=2.10(1.13-3.89), P=0.018]. CONCLUSIONS: Severe COVID-19 patients with COPD have higher levels of disease severity, proportion of progression to critical illness and mortality rate. Individualized treatment strategies should be adopted to improve the prognosis of severe COVID-19 patients.

Characteristics and outcomes of 7620 Multiple Sclerosis patients admitted with COVID-19 in the United States (preprint)

Background At the start of the COVID-19 pandemic, several experts raised concerns about its impact on Multiple Sclerosis (MS) patients. Several small sample studies were published throughout the pandemic highlighting certain risk factors and outcomes. This study aims to provide a perspective using the biggest inpatient database from the United States. Method We screened for COVID-19 cases between April to December 2020, via the 2020 National Inpatient Sample (NIS). Characteristics of COVID-19 patients with and without MS were studied. The odds of mortality, mechanical ventilation and non-invasive ventilation were also analyzed. Finally, we investigated the risk factors of various outcomes among MS patients. Results We identified 1,628,110 hospitalizations with COVID-19, including 7620 (0.5%) MS patients. 68.6% of MS cases were Whites, and 63.3% were covered by Medicare. Compared to non-MS patients, MS patients with COVID-19 were mostly Females, had depression, peripheral vascular disease, and smoked. However, MS patients had lower cases of alcohol abuse, obesity, hyperlipidemia, diabetes, hypertension, CKD, or maintenance dialysis. MS patients with COVID-19 were also younger (mean age 60.65 years vs. 62.60 years, p<0.01). 8.9% of MS patients with COVID-19 did not survive their hospitalization, and it was lower than non-MS cases (12.9%, aOR 0.783, 95% CI 0.721-0.852, p<0.01). Less MS patients with COVID-19 needed non-invasive ventilation (4.5% vs. 6.4%, aOR 0.790, 95% CI 0.706-0.883, p<0.01) and mechanical ventilation (9.0% vs. 11.2%, aOR 1.017, 95% CI 0.937-1.104, p=0.687). Furthermore, MS patients with COVID-19 reported higher odds of non-invasive ventilation if they were of ages 60 and above (aOR 2.124, p<0.01), had chronic pulmonary disease (aOR 1.691, p<0.01), obesity (aOR 1.69, p<0.01), and diabetes (aOR 1.573, p<0.01). Private insurance beneficiaries showed reduced risk compared to Medicare (aOR 0.523, p<0.01). Similarly, for mechanical ventilation, those ages 60 and above (aOR 1.404, p<0.01), alcohol abuse (aOR 6.404, p<0.01), obesity (aOR 1.417, p<0.01), diabetes (aOR 1.992, p<0.01), hypertension (aOR 1.269, p=0.016), or dialysis (aOR 3.003, p<0.01) had higher odds, while females (aOR 0.700, p<0.01), smokers (aOR 0.588, p<0.01), and those with depression (aOR 0.698, p<0.01) or hyperlipidemia (aOR 0.711, p<0.01) showed reduced odds. Our study further found higher odds of mortality among those of age 60 and above (aOR 3.813, p<0.01), chronic pulmonary disease (aOR 1.739, p<0.01), obesity (aOR 1.425, p<0.01), CKD (aOR 1.982, p<0.01), or a history of old MI (aOR 1.864, p<0.01) while females (aOR 0.610, p<0.01), smokers (aOR 0.770, p<0.01), as well as those with depression (aOR 0.695, p<0.01), and hyperlipidemia (aOR 0.769, p<0.01) showed better outcomes. Blacks had lower odds of dying (aOR 0.636, p<0.01), whereas Hispanics had higher odds of dying (aOR 1.674, p<0.01), compared to Whites. Medicaid and Privately insured patients had lower odds of dying compared to Medicare i.e. (aOR 0.435, p<0.01), and (aOR 0.488, p<0.01), respectively. Conclusion We found several differences in patient characteristics among MS and non-MS patients with COVID-19. MS patients were also less likely to die or require non-invasive ventilation than non-MS patients. Further risk factors influencing the different outcomes among MS patients were also identified.

Risk Factors and Predictive Modeling for Post-Acute Sequelae of SARS-CoV-2 Infection: Findings from EHR Cohorts of the RECOVER Initiative (preprint)

Background Patients who were SARS-CoV-2 infected could suffer from newly incidental conditions in their post-acute infection period. These conditions, denoted as the post-acute sequelae of SARS-CoV-2 infection (PASC), are highly heterogeneous and involve a diverse set of organ systems. Limited studies have investigated the predictability of these conditions and their associated risk factors. Method In this retrospective cohort study, we investigated two large-scale PCORnet clinical research networks, INSIGHT and OneFlorida+, including 11 million patients in the New York City area and 16.8 million patients from Florida, to develop machine learning prediction models for those who are at risk for newly incident PASC and to identify factors associated with newly incident PASC conditions. Adult patients aged  20 with SARS-CoV-2 infection and without recorded infection between March 1st, 2020, and November 30th, 2021, were used for identifying associated factors with incident PASC after removing background associations. The predictive models were developed on infected adults. Results We find several incident PASC, e.g., malnutrition, COPD, dementia, and acute kidney failure, were associated with severe acute SARS-CoV-2 infection, defined by hospitalization and ICU stay. Older age and extremes of weight were also associated with these incident conditions. These conditions were better predicted (C-index >0.8). Moderately predictable conditions included diabetes and thromboembolic disease (C-index 0.7-0.8). These were associated with a wider variety of baseline conditions. Less predictable conditions included fatigue, anxiety, sleep disorders, and depression (C-index around 0.6). Conclusions This observational study suggests that a set of likely risk factors for different PASC conditions were identifiable from EHRs, predictability of different PASC conditions was heterogeneous, and using machine learning-based predictive models might help in identifying patients who were at risk of developing incident PASC. 

The impact of facemask on patients with COPD: A systematic review and meta-analysis.

Background: Since the emergence of COVID-19, mandatory facemask wearing has been implemented around the world to prevent viral transmission, however, the impact of wearing facemasks on patients with COPD was unclear. Methods: The current study undertakes a systematic review and meta-analysis of a comprehensive literature retrieval from six databases, based on the pre-determined eligibility criteria, irrespective of language. The risk of bias was assessed using an established instrument. We primarily focused on analyzing ETCO2, SpO2, and heart and respiratory rates, and also considered the impacts on physiological and exercise performance. A descriptive summary of the data and possible meta-analysis was performed. Forest plots were generated to pool estimates based on each of the study outcomes. Results: Of the 3,751 publications considered, six publications were selected for a systematic review and two publications were included for meta-analysis, however, the quality of these six studies was relatively low overall. In the case of inactivity, the facemask wearing COPD cohort had higher respiratory rates than that of the non-facemask wearing cohort (MD = 1.00 and 95% CI 0.47-1.53, P < 0.05). There was no significant difference in ETCO2 (MD = 0.10 and 95% CI -1.57-1.78, P > 0.05) and heart rate (MD = 0.40 and 95% CI -3.59-4.39, P > 0.05) nor SpO2 (MD = -0.40 and 95% CI -0.84-0.04, P > 0.05) between the COPD patients with and without facemasks. Furthermore, it was observed that the only significant differences between the COPD patients with and without facemasks undertaking different activities were FEV1 (%) (MD = 3.84 and 95% CI 0.14-7.54, P < 0.05), FEV1/FVC (%) (MD = 3.25 and 95% CI 0.71-5.79, P < 0.05), and blood lactate (MD = -0.90 and 95% CI -1.73 to -0.07, P < 0.05). Conclusion: Wearing facemasks decreased the exercise performance of patients with COPD, however, it had minimal impact on physiological indexes. Further investigations will be performed on the high-quality data from randomized control studies. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=326265, identifier: CRD42022326265.

COVID-19's impact on care practice for alpha-1-antitrypsin deficiency patients.

BACKGROUND: Patients with alpha-1 antitrypsin deficiency (AATD), commonly categorized as a rare disease, have been affected by the changes in healthcare management brought about by COVID-19. This study's aim was to identify the changes that have taken place in AATD patient care as a result of the COVID-19 pandemic in Spain and to propose experts' recommendations aimed at ensuring humanized and quality care for people with AATD in the post-pandemic situation. METHODS: A qualitative descriptive case study with a holistic single-case design was conducted, using focus groups with experts in AATD clinical management, including 15 health professionals with ties to the Spanish health system (12 pneumologists and 2 hospital pharmacists from 11 different hospitals in Spain) and 1 patient representative. RESULTS: COVID-19 has had a major impact on numerous aspects of AATD clinical patient management in Spain, including diagnostic, treatment, and follow-up phases. The experts concluded that there is a need to strengthen coordination between Primary Care and Hospital Care and improve the coordination processes across all the organizations and actors involved in the healthcare system. Regarding telemedicine and telecare, experts have concluded that it is necessary to promote this methodology and to develop protocols and training programs. Experts have recommended developing personalized and precision medicine, and patient participation in decision-making, promoting self-care and patient autonomy to optimize their healthcare and improve their quality of life. The possibility of monitoring and treating AATD patients from home has also been proposed by experts. Another result of the study was the recommendation of the need to ensure that plasma donations are made on a regular basis by a sufficient number of healthy individuals. CONCLUSION: The study advances knowledge by highlighting the challenges faced by health professionals and changes in AATD patient management in the context of the COVID-19 pandemic. It also proposes experts' recommendations aimed at ensuring humanized and quality care for people with AATD in the post-pandemic situation. This work could serve as a reference study for physicians on their daily clinical practice with AATD patients and may also provide guidance on the changes to be put in place for the post-pandemic situation.

Reducing the Risk of Mortality in Chronic Obstructive Pulmonary Disease With Pharmacotherapy: A Narrative Review.

In 2020, chronic obstructive pulmonary disease (COPD) was the fifth leading cause of death in the United States excluding COVID-19, and its mortality burden has been rising since the 1980s. Smoking cessation, long-term oxygen therapy, noninvasive ventilation, and lung volume reduction surgery have had a beneficial effect on mortality; however, until recently, the effects of pharmacologic therapies on all-cause mortality have been unclear. Inhaled pharmacologic treatments for patients with COPD include combinations of long-acting muscarinic receptor antagonists (LAMAs), long-acting-ß2-agonists (LABAs), and inhaled corticosteroids (ICS). The recent IMPACT and ETHOS clinical trials reported mortality benefits with ICS/LAMA/LABA triple therapy compared with LAMA/LABA dual therapy. In IMPACT, fluticasone furoate/umeclidinium/vilanterol therapy significantly reduced the risk of on-/off-treatment all-cause mortality vs umeclidinium/vilanterol (hazard ratio, 0.72; 95% CI, 0.53 to 0.99; P=.042). The ETHOS trial found a reduction in the risk of on-/off-treatment all-cause mortality in patients treated with budesonide/glycopyrrolate/formoterol vs glycopyrrolate/formoterol (hazard ratio, 0.51 [0.33 to 0.80]; nominal P=.0035). Both trials included populations of patients with symptomatic COPD at high risk of future exacerbations, and a post hoc analysis of the final retrieved vital status data suggested that the observed mortality benefits are conferred by the ICS component. In conclusion, triple therapy reduces the risk of mortality in patients with symptomatic COPD characterized by moderate or severe airflow obstruction and a recent history of moderate or severe exacerbations. This benefit is likely to be driven by reductions in exacerbations. Future research efforts should focus on improving the long-term prognosis of patients living with COPD.

Sevoflurane sedation in COVID-19 acute respiratory distress syndrome: an observational study with a propensity score matching model (preprint)

Background: Patients that are affected by severe induced respiratory failure (C-ARDS) formCOVID-19, frequently need deep sedation in order to perform adequate ventilator support. Volatile anesthetics (VAs) constitute a convenient alternative to intravenous molecules, allowing to fine-tune the desired level of sedation. Moreover, VAs might have anti-inflammatory and bronchodilatatory effects, which are particularly appropriate for COVID-19 patients. Methods: In this study, we show the results of a retrospective single-center non-profit observational cohort study. To achieve this, we enrolled patients hospitalized for C-ARDS in the COVID Intensive Care Unit of Hospital Santo Stefano (Prato, Italy) during the period March 2020 - June 2021. A total of 112 patients were enrolled in the study that were all submitted to invasive mechanical ventilation. Participants were divided in two groups: i) Group 1 received the VA sevoflurane and, ii) Group 2 were sedated with propofol and remifentanil. A propensity score matching model (PSM) was applied in order match each treated unit with a non-treated unit of similar characteristics between the two groups. The calculation of PSM was performed considering anthropometric data such as age, sex, body mass index (BMI) and comorbidities such as arterial hypertension, chronic obstructive pulmonary disease (COPD), ischemic heart disease, and chronic kidney damage as covariates. Level of sedation (BIS monitoring), respiratory and ventilator parameters, i.e., PaO2/FiO2, pulmonary static compliance and positive end expiratory pressure (PEEP) and biochemical parameters were evaluated at three time-points: at the time of the invasive ventilation (T1), after 72 hours (T2) and after 7 days (T3). Results: 56 patients who received inhaled sedation with sevoflurane were matched with 56 participants receiving an intravenous sedation by means of PSM. An adequate level of sedation was obtained in both groups. In the sevoflurane group, an increase of PaO2/FiO2 and of the static compliance was observed while mortality was slightly decreased. Conclusions: In this work, we demonstrate that deep sedation of invasively ventilated C-ARDS patients can be effectively obtained with sevoflurane. Interestingly, VA sedation with sevoflurane contributed to enhance respiratory mechanics, which has a clear clinical relevance in C-ARDS patients. In terms of pulmonary compliance, results obtained after three days of starting sedation therapy with sevoflurane demonstrated that static compliance was higher in those who received inhaled sedation. At the same timing, PaO2/FiO2 ratio at the same timing was greater in group 1 than in group 2. Further studies deem to confirm the potential of this treatment in a randomized clinical trial.

Effects of a home-based pulmonary rehabilitation program with and without telecoaching on health-related outcomes in COVID-19 survivors: a randomized controlled clinical study.

OBJECTIVE: To compare the effects of a home-based pulmonary rehabilitation (PR) program with and without telecoaching on health-related outcomes in COVID-19 survivors. METHODS: A total of 42 COVID-19 patients who completed medical treatment were randomly divided into two groups: the study (telecoaching) group (n = 21) and the control (no telecoaching) group (n = 21). Both groups participated in an 8-week home-based PR program including education, breathing exercises, strength training, and regular walking. The study group received phone calls from a physiotherapist once a week. Both groups of patients were assessed before and after the program by means of the following: pulmonary function tests; the modified Medical Research Council dyspnea scale; the six-minute walk test; extremity muscle strength measurement; the Saint George's Respiratory Questionnaire (to assess disease-related quality of life); the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36, to assess overall quality of life); and the Hospital Anxiety and Depression Scale. RESULTS: In both groups, there were significant improvements in the following: FVC; the six-minute walk distance; right and left deltoid muscle strength; Saint George's Respiratory Questionnaire activity domain, impact domain, and total scores; and SF-36 social functioning, role-physical, role-emotional, and bodily pain domain scores (p < 0.05). Decreases in daily-life dyspnea, exertional dyspnea, and exertional fatigue were significant in the study group (p < 0.05), and the improvement in SF-36 social functioning domain scores was greater in the study group (p < 0.05). CONCLUSIONS: A home-based PR program with telecoaching increases social functioning and decreases daily-life dyspnea, exertional dyspnea, and exertional fatigue in COVID-19 survivors in comparison with a home-based PR program without telecoaching.

Randomized controlled trial of home-based vs. hospital-based pulmonary rehabilitation in post COVID-19 patients.

BACKGROUND: Between 30% and 60% of people who have been infected with COVID-19 still had symptoms 3 months after the start of the disease. Prescribing a pulmonary rehabilitation program in rehabilitation facilities for post COVID-19 patients could help alleviate the symptoms. However, rehabilitation facilities known to provide good quality care to COVID-19 patients and all other patients, could become saturated by the rise in cases. Home-based rehabilitation is a potential solution that could be sustainable in the long term to avoid this saturation and/or a very long waiting list for patients. AIM: The aim of this study was to investigate whether home-based rehabilitation would have similar effects compared to inpatient rehabilitation on physical and respiratory variables in post COVID-19 patients. DESIGN: This is a randomized controlled trial. SETTING: Pulmonary rehabilitation facility. POPULATION: Seventeen post COVID-19 patients were randomized into two groups: inpatient pulmonary rehabilitation (IPR) or home-based pulmonary rehabilitation (HPR). METHODS: The comparison of the two rehabilitation methods relied on questionnaires, physical tests and the evaluation of several respiratory parameters. A 2-way Analysis of Variance (ANOVA) with repeated measures was performed to assess the effects of time (pre- vs. post-rehabilitation), group (IPR vs. HPR) and their interaction for all parameters. RESULTS: The main result of this study is that distance covered in the 6MWT (6MWD) shows significant improvements, between pre- and postrehabilitation program in both groups (+95 m in IPR group vs.+72 m in HPR group, P<0.001) with no significant interaction between time and group (P=0.420). CONCLUSIONS: These results suggest that home-based pulmonary rehabilitation would be as efficient as IPR to decrease physical sequelae in post COVID-19 patients. CLINICAL REHABILITATION IMPACT: It is possible to suggest both methods (home-based rehabilitation or inpatient pulmonary rehabilitation) according to the specificities of each patient and depending on hospital saturation. The choice of one or the other method should not be made to the detriment of the patient.

Risk factors for postoperative medical morbidity and 3-month mortality in elderly patients with hip fracture following hip arthroplasty during COVID-19 pandemic.

BACKGROUND: The purpose of the current study was to investigate the incidence of postoperative medical complications and 3-month mortality in patients ≥ 70 years old with hip fracture following hip arthroplasty (HA) and independent risk factors associated with postoperative medical complications and 3-month mortality during the Coronavirus Disease 2019 (COVID-19) pandemic. METHODS: A multicenter retrospective study was conducted, patients ≥ 70 years old with HA for hip fracture under general anesthesia were included during COVID-19 and before COVID-19 pandemic. The outcome was defined as postoperative medical complications and 3-month mortality. The baseline characteristics and risk factors were collected, multivariable logistic regression was used to identify independent risk factors for postoperative medical complications and 3-month mortality. RESULTS: A total of 1096 patients were included during COVID-19 pandemic and 1149 were included before COVID-19 pandemic in the study. Patients ≥ 70 years with hip fracture for HA had longer fracture to operation duration (7.10 ± 3.52 vs. 5.31 ± 1.29, P < 0.001), and the incidence of postoperative medical complications (21.90% vs. 12.53%, P < 0.001) and 3-month mortality (5.20% vs. 3.22%, P = 0.025) was higher during COVID-2019 pandemic. Multivariate logistic regression analysis showed that dementia (OR 2.73; 95% CI 1.37-5.44; P = 0.004), chronic obstructive pulmonary disease (COPD) (OR 3.00; 95% CI 1.92-4.71; P < 0.001), longer fracture to operation duration (OR 1.24; 95% CI 1.19-1.30; P < 0.001) were associated with increased risk for postoperative medical complications. COPD (OR 2.10; 95% CI 1.05-4.17; P = 0.035), dementia (OR 3.00; 95% CI 1.11-7.94; P = 0.031), postoperative medical complications (OR 4.99; 95% CI 2.68-9.28; P < 0.001), longer fracture to operation duration (OR 1.11; 95% CI 1.04-1.19; P = 0.002) were associated with increased risk for 3-month mortality. CONCLUSIONS: In conclusion, we found that postoperative medical morbidity and 3-month mortality in patients with hip fracture underwent HA were 21.90% and 5.20%, respectively, during the COVID-19. COPD, dementia and longer fracture to operation duration were associated with negative outcome in patients with hip fracture underwent HA during the COVID-19.

Just breathe: a review of sex and gender in chronic lung disease.

Chronic lung diseases are the third leading cause of death worldwide and are increasing in prevalence over time. Although much of our traditional understanding of health and disease is derived from study of the male of the species - be it animal or human - there is increasing evidence that sex and gender contribute to differences in disease risk, prevalence, presentation, severity, treatment approach, response and outcomes. Chronic obstructive pulmonary disease, asthma and bronchiectasis represent the most prevalent and studied chronic lung diseases and have key sex- and gender-based differences which are critical to consider and incorporate into clinical and research approaches. Mechanistic differences present opportunities for therapeutic development whereas behavioural and clinical differences on the part of patients and providers present opportunities for greater education and understanding at multiple levels. In this review, we seek to summarise the sex- and gender-based differences in key chronic lung diseases and outline the clinical and research implications for stakeholders.