Physical activity,COVID-19,and respiratory comorbidities:The good,the bad,and the ugly

Almost 3 years after the outbreak of the novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)responsible for the coronavirus disease 2019(COVID-19)that has caused more than 6 million deaths worldwide,1the pandemic persists and hampers our daily lives.There are at least 2 main reasons explaining why we still struggle to terminate this pandemic.First,novel variants of concern of SARS-CoV-2unceasingly emerge despite almost 12 billion doses of vaccinebeing administered to date.

Outcomes and Cost Effectiveness of a Respiratory Coordinated Care Program in Patients with Severe or Very Severe COPD

Multidisciplinary community coordinated care programs are widely adopted to optimise care of chronic disease patients, but there is a need for further evaluation in the setting of COPD. This observational study evaluated 147 patients with severe or very severe COPD who were enrolled in a multidisciplinary community respiratory coordinated care program (RCCP) from 2007 to 2012. Comparison was made of hospitalisation rates and length of stay for 12 months prior to joining the program, and the first 12 months after joining the program. This data was used to inform a cost analysis. Enrolment into RCCP halved the annual hospital admission rate from 1.18 to 0.57 admissions per year (relative risk reduction 51.4%, p < 0.001), and annual total length of stay was reduced from 8.06 to 3.59 days per patient per year (p < 0.001). Hospital admissions were reduced from 5.05 days to 2.00 days (p < 0.001). Accounting for the program’s costs, these changes resulted in a $US 906.94 ($AUD 972.80) cost saving per patient per year. A RCCP program can reduce patient hospitalisation and overall costs in the COPD setting.

Levels of CMV-reactive antibodies correlate with the induction of CD28^null T cells and systemic inflammation in chronic obstructive pulmonary disease （COPD）

Chronic obstructive pulmonary disease （COPD） is characterized by chronic irreversible inflammation and progressive decline in lung function. While smoking and other environmental agents （e.g., air pollutants） are common causes of COPD, the major challenges in managing this condition are the persistent inflammation and functional deterioration which are not reversed by removal of precipitating agents （e.g., smoking cessation） or treatment with anti-inflammatory agents.

Workup of difficult-to-treat asthma:implications from treatable

Traditional stepwise approach usually adjusts the treatment regimen based on changes in asthma symptoms and severity to achieve good asthma control.However,due to the generalized heterogeneity and complexity of asthma,its therapeutic efficacy in difficultto-treat asthma is limited.Recently,a precision medicine approach based on the identification and intervention of treatable traits of chronic airway disease has been proposed and appears to be of greater benefit to asthmatics.We reported a 71-year-old male with uncontrolled asthma and multiple exacerbations over the past year.He complained of persistent dyspnea despite high-dose of inhaled corticosteroids plus other controllers.Does this patient have some potential treatable traits contributing to difficult-to-treat asthma?Through a multidimensional assessment of three domains including pulmonary,extrapulmonary,and behavioral/risk factors,15 treatable traits were identified in the patient,mainly including airflow limitation,eosinophilic airway inflammation,small airway dysfunction,exacerbation prone,dilated cardiomyopathy,diabetes mellitus,inhaler device polypharmacy,smoking,and the absence of an asthma action plan.After targeted treatment for these treatable traits,the patient experienced significant improvement in dyspnea and he could maintain good asthma control with low-dose inhaled corticosteroids and long-acting β_(2)-agonist.This study shows that,in response to the limitation of a stepwise approach to therapy,treatable traits is a new strategy where patients are individually assessed for a specified set of treatable problems,and an individualized treatment program is developed and implemented based on this multidimensional assessment,especially for difficult-to-treat asthma.

Existing tests vs. novel non-invasive assays for detection of invasive aspergillosis in patients with respiratory diseases

Background: Although existing mycological tests (bronchoalveolar lavage [BAL] galactomannan [GM], serum GM, serum (1,3)-β-D-glucan [BDG], and fungal culture) are widely used for diagnosing invasive pulmonary aspergillosis (IPA) in non-hematological patients with respiratory diseases, their clinical utility in this large population is actually unclear. We aimed to resolve this clinical uncertainty by evaluating the diagnostic accuracy and utility of existing tests and explore the efficacy of novel sputum-basedAspergillus assays.Methods: Existing tests were assessed in a prospective and consecutive cohort of patients with respiratory diseases in West China Hospital between 2016 and 2019 while novel sputum assays (especially sputum GM andAspergillus-specific lateral-flow device [LFD]) in a case-controlled subcohort. IPA was defined according to the modified European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. Sensitivity and specificity were computed for each test and receiver operating characteristic (ROC) curve analysis was performed.Results: The entire cohort included 3530 admissions (proven/probable IPA=66, no IPA=3464) and the subcohort included 127 admissions (proven/probable IPA=38, no IPA=89). Sensitivity of BAL GM (≥1.0 optical density index [ODI]: 86% [24/28]) was substantially higher than that of serum GM (≥0.5 ODI: 38% [39/102]) (χ^(2)=19.83,P<0.001), serum BDG (≥70 pg/mL: 33% [31/95]) (χ^(2)=24.65,P<0.001), and fungal culture (33% [84/253]) (χ^(2)=29.38,P<0.001). Specificity varied between BAL GM (≥1.0 ODI: 94% [377/402]), serum GM (≥0.5 ODI: 95% [2130/2248]), BDG (89% [1878/2106]), and culture (98% [4936/5055]). Sputum GM (≥2.0 ODI) had similar sensitivity (84% [32/38]) (Fisher’s exactP=1.000) to and slightly lower specificity (87% [77/89]) (χ^(2)=5.52,P=0.019) than BAL GM (≥1.0 ODI). Area under the ROC curve values were comparable between sputum GM (0.883 [0.812-0.953]) and BAL GM (0.901 [0.824-0.977]) (P=0.734). Sputum LFD had similar specificity (91% [81/89]) (χ^(2)=0.89,P=0.345) to and lower sensitivity (63% [24/38]) (χ^(2)=4.14,P=0.042) than BAL GM (≥1.0 ODI), but significantly higher sensitivity than serum GM (≥0.5 ODI) (χ^(2)=6.95,P=0.008), BDG (χ^(2)=10.43,P=0.001), and fungal culture (χ^(2)=12.70,P<0.001).Conclusions: Serum GM, serum BDG, and fungal culture lack sufficient sensitivity for diagnosing IPA in respiratory patients. Sputum GM and LFD assays hold promise as rapid, sensitive, and non-invasive alternatives to the BAL GM test.

妊娠期重症哮喘恶化

Objective: To estimate the frequency of severe asthma exacerbations in pregnant women and to estimate whether there is an association with adverse perinatal outcomes. METHODS: Asthma exacerbations were evaluated in 146 women who were enrolled in a prospective cohort study of asthma and pregnancy. A severe exacerbation was defined as a hospital admission, emergency department presentation,or unscheduled doctor visit for asthma or a course of oral corticosteroids. Women were classified as having mild (n = 63), moderate (n = 34), or severe (n = 49) asthma. RESULTS: Severe exacerbations occurred in 8%(95%confidence interval [CI] 1.3-14.6%) of women with mild asthma, 47%(95%CI 30.3-63.8%) of women with moderate asthma, and 65%(95%CI 52-78.6%) of women with severe asthma at a mean gestational age of 25.1 ±0.9 (range 9-39) weeks of gestation. Among women who had severe exacerbations, there were 2 male stillbirths (P = .102) and a significantly increased rate of male low birth weight (P = .03). Maternal age, lung function, body mass index, gravidity, and parity were not different between women who did or those who did not have a severe exacerbation. Maternal pregnancy weight gain was significantly lower in women who had a severe exacerbation (P = .039). Forty-three percent of severe exacerbations occurred in winter, 34%were associated with self-reported viral infection, and 29%with nonadherence to inhaled corticosteroid medication. CONCLUSION: The exacerbation rate among pregnant women with asthma is high and associated with poor outcomes for the male fetus. Improvements in asthma management to prevent severe exacerbations may lead to a better outcome for both mother and baby.

Current asthma control predicts future risk of asthma exacerbation： a 12-month prospective cohort study

Background The performance of asthma control test （ACT） at baseline for predicting future risk of asthma exacerbation has not been previously demonstrated. This study was designed to explore the ability of the baseline ACT score to predict future risk of asthma exacerbation during a 12-month follow-up. Methods This post hoc analysis included data from a 12-month prospective cohort study in patients with asthma （n=290）. The time to the first asthma exacerbation was analyzed and the association between baseline ACT scores and future risk of asthma exacerbation was calculated as adjusted odds ratio （OR） using Logistic regression models. Further, sensitivity and specificity were estimated at each cut-point of ACT scores for predicting asthma exacerbations. Results The subjects were divided into three groups, which were uncontrolled （U, n=128）, partly-controlled （PC, n=111）, and well controlled （C, n=51） asthma. After adjustment, the decreased ACT scores at baseline in the U and PC groups were associated with an increased probability of asthma exacerbations （OR 3.65 and OR 5.75, respectively）, unplanned visits （OR 8.03 and OR 8.21, respectively） and emergency visits （OR 20.00 and OR 22.60, respectively） over a 12-month follow-up period. The time to the first asthma exacerbation was shorter in the groups with U and PC asthma （all P 〈0.05）. The baseline ACT of 20 identified as the cut-point for screening the patients at high risk of asthma exacerbations had an increased sensitivity of over 90.0% but a lower specificity of about 30.0%. Conclusion Our findings indicate that the baseline ACT score with a high sensitivity could rule out patients at low risk of asthma exacerbations and predict future risk of asthma exacerbations in clinical practice.

Management of severe asthma:from stepwise approach to therapy to treatable traits?

Dear Editor,Asthma is a heterogeneous disease,usually characterized by chronic airway inflammation.The disease affects more than 300 million individualsworldwide,and poses a significant ongoing health burden,especially for patients with poorly controlled and severe asthma.1 The stepwise approach to therapy recommended in asthma management guidelines is effective.

治疗学 控制不佳的哮喘治疗

一名35岁男性,既往诊断轻度哮喘,他告知家庭医生,在过去3个月中他间断在夜间咳醒或因气短而憋醒。他是一名厨师,现在已经感到难以完成轮班工作。长期以来,他每天吸入2次倍氯米松200μg,由于持续发作的症状,他询问是否需要改变治疗。控制不佳的哮喘或中度哮喘是指患者每天有哮喘症状。

Impaired CTLA-4 responses in COPD are associated with systemic inflammation

Systemic inflammation is a feature of chronic obstructive pulmo- nary disease （COPD）. Defects in T cell-mediated anti-inflamma- tory pathways such as cytotoxic T lymphocyte antigen-4 （CTLA- 4） may promote damaging inflammation. This study provides novel data implicating the impaired induction of an anti-inflam- matory molecule, CTLA-4 in the elevated inflammation observed in COPD patients. Low induction of CTLA-4 in COPD patients paralleled increased markers of systemic inflammation ex vivo and increased T-cell responses to a bacterial superantigen, staphylo- coccal enterotoxin-B （SEB） in vitro. This mechanism may explain the increased inflammation in COPD patients.