Earlier diagnosis improves COVID-19 prognosis: a nationwide retrospective cohort analysis.

BACKGROUND: Risk of adverse outcomes in COVID-19 patients by stratifying by the time from symptom onset to confirmed diagnosis status is still uncertain. METHODS: We included 1,590 hospitalized COVID-19 patients confirmed by real-time RT-PCR assay or high-throughput sequencing of pharyngeal and nasal swab specimens from 575 hospitals across China between 11 December 2019 and 31 January 2020. Times from symptom onset to confirmed diagnosis, from symptom onset to first medical visit and from first medical visit to confirmed diagnosis were described and turned into binary variables by the maximally selected rank statistics method. Then, survival analysis, including a log-rank test, Cox regression, and conditional inference tree (CTREE) was conducted, regarding whether patients progressed to a severe disease level during the observational period (assessed as severe pneumonia according to the Chinese Expert Consensus on Clinical Practice for Emergency Severe Pneumonia, admission to an intensive care unit, administration of invasive ventilation, or death) as the prognosis outcome, the dependent variable. Independent factors included whether the time from symptom onset to confirmed diagnosis was longer than 5 days (the exposure) and other demographic and clinical factors as multivariate adjustments. The clinical characteristics of the patients with different times from symptom onset to confirmed diagnosis were also compared. RESULTS: The medians of the times from symptom onset to confirmed diagnosis, from symptom onset to first medical visit, and from first medical visit to confirmed diagnosis were 6, 3, and 2 days. After adjusting for age, sex, smoking status, and comorbidity status, age [hazard ratio (HR): 1.03; 95% CI: 1.01-1.04], comorbidity (HR: 1.84; 95% CI: 1.23-2.73), and a duration from symptom onset to confirmed diagnosis of >5 days (HR: 1.69; 95% CI: 1.10-2.60) were independent predictors of COVID-19 prognosis, which echoed the CTREE models, with significant nodes such as time from symptom onset to confirmed diagnosis, age, and comorbidities. Males, older patients with symptoms such as dry cough/productive cough/shortness of breath, and prior COPD were observed more often in the patients who procrastinated before initiating the first medical consultation. CONCLUSIONS: A longer time from symptom onset to confirmed diagnosis yielded a worse COVID-19 prognosis.

The Interactions of Airway Bacterial and Fungal Communities in Clinically Stable Asthma.

Dysbiotic airway microbiota play important roles in the inflammatory progression of asthma, and exploration of airway microbial interactions further elucidates asthma pathogenesis. However, little is known regarding the airway bacterial-fungal interactions in asthma patients. We conducted a cross-sectional survey of the sputum bacterial and fungal microbiota from 116 clinically stable asthma patients and 29 healthy controls using 16S rRNA gene and ITS1 sequencing. Compared with healthy individuals, asthma patients exhibited a significantly altered microbiota and increased bacterial and fungal alpha diversities in the airway. Microbial genera Moraxella, Capnocytophaga, and Ralstonia (bacteria) and Schizophyllum, Candida, and Phialemoniopsis (fungi) were more abundant in the asthma airways, while Rothia, Veillonella and Leptotrichia (bacteria) and Meyerozyma (fungus) were increased in healthy controls. The Moraxellaceae family and their genus Moraxella were significantly enriched in asthma patients compared with healthy controls (80.5-fold, P = 0.007 and 314.7-fold, P = 0.027, respectively). Moreover, Moraxellaceae, along with Schizophyllum, Candida, and Aspergillus (fungal genera), were positively associated with fungal alpha diversity. Correlation networks revealed 3 fungal genera (Schizophyllum, Candida, and Aspergillus) as important airway microbes in asthma that showed positive correlations with each other and multiple co-exclusions with other common microbiota. Moraxellaceae members were positively associated with asthma-enriched fungal taxa but negatively related to several healthy-enriched bacterial taxa. Collectively, our findings revealed an altered microbiota and complex microbial interactions in the airways of asthma patients. The Moraxellaceae family and their genus Moraxella, along with 3 important fungal taxa, showed significant interactions with the airway microbiota, providing potential insights into the novel pathogenic mechanisms of asthma.

Continuous positive airway pressure improves respiratory mechanics and efficiency of neural drive in stable COPD: an exploratory study.

BACKGROUND: Continuous positive airway pressure (CPAP) is a major treatment strategy for severe chronic obstructive pulmonary disease (COPD), especially with respiratory failure. However, it remains inconclusive whether CPAP affects respiratory mechanics and neural drive in stable COPD patients without respiratory failure. METHODS: Twenty-two COPD patients without respiratory failure received CPAP starting from 4 to 10 cmH2O in 1 cmH2O increments. Respiratory pattern, end expiatory lung volume (EELV), dynamic PEEPi (PEEPidyn), airway resistance (Raw), pressure-time product of diaphragmatic pressure (PTPdi) and esophageal pressure (PTPeso), root mean square (RMS) of diaphragm electromyogram (EMGdi) and ratio of ventilation (Ve) to EMGdi (i.e., Ve/RMS) were measured before and at each level of continue positive airway pressure (CPAP). A subgroup analysis was performed between patients with and without inspiratory muscle weakness. RESULTS: Nineteen patients completed the treatment. The respiratory pattern improved significantly after CPAP. Raw, PTPdi, and Pdi decreased significantly. ΔEELV decreased at 4 cmH2O (P<0.05), but increased significantly at >8 cmH2O. PEEPidyn decreased from 2.18±0.98 to 1.37±0.55 cmH2O. RMS increased while Ve/RMS improved significantly after CPAP (P<0.05). Besides, CPAP could significantly improve respiratory mechanics in patients with inspiratory muscle weakness. CONCLUSIONS: CPAP improves respiratory pattern, PEEPi, Raw, work of breathing and efficiency of neural drive in COPD patients without respiratory failure, but easily increases dynamic pulmonary hyperinflation. These effects on respiratory mechanics are significant in patients with inspiratory muscle weakness.

Comparison of the clinical characteristics and comprehensive assessments of the 2011 and 2017 GOLD classifications for patients with COPD in China.

OBJECTIVE: Compared with the 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD), there have been significant changes in the 2017 GOLD classification. The purpose of this study was to analyze the changes in clinical characteristics of the new A-B-C-D system and to explore its role in comprehensive assessment of COPD. SUBJECTS AND METHODS: A total of 631 stable COPD patients were included in a cross-sectional survey. Data collected included baseline data and pulmonary function testing results, respiratory muscle strength, symptoms and quality of life, exercise capacity, nutritional status, and anxiety and depression as a comprehensive assessment. Based on the 2011 GOLD and 2017 GOLD classifications, patients were divided into Groups A1-D1 and Groups A2-D2, respectively. RESULTS: In the 2011 GOLD, 64 subjects in Group C1 were reclassified into Group A2 (41.6%), while 77 subjects in Group D1 were reclassified into Group B2 (27.1%). The old and new grading systems were somewhat consistent (Cohen's kappa=0.6963, P<0.001). Lung function was lower, while the body mass index, airflow obstruction, dyspnea, and exercise capacity index (BODE index) was higher in Group A2 than in Group A1 (P<0.001). In Group B2, lung function, 6-minute walking distance (6MWD), and respiratory muscle strength were significantly lower than in Group B1 (P<0.001), while the BODE index (P<0.001) was higher. In comprehensive assessment, subjects in Groups B2 and D2 had significantly lower lung function, 6MWD, respiratory muscle strength, quality of life, higher symptom scores, and BODE index than subjects in Group A2 (P<0.001). The differences between Group A2 and C2 were small. CONCLUSION: Compared with the 2011 GOLD, the 2017 GOLD reclassified more patients into Groups A and B, those with significantly worse lung function and higher BODE index. In the comprehensive assessment of the new classification, Groups B and D may have greater disease severity. However, the effectiveness of the new grading system in predicting patient prognosis, and its guidance on the use of drugs, remains to be explored in future studies.

[Post-therapeutic change of cathelicidin LL-37 in asthmatics of different inflammatory phenotypes].

OBJECTIVE: To explore the post-therapeutic change of cathelicidin LL-37 in asthmatics of different inflammatory phenotypes. METHODS: Thirty-four patients with initially diagnosed asthma (asthma group) and 14 normal subjects (control group) were recruited at Nanfang Hospital from August 2009 to August 2010 for this prospective study. Sputum and venous blood samples were collected and analyzed for cell differential. Eosinophilic asthma was defined as the count of sputum eosinophils ≥ 3%. The LL-37 concentrations in plasma and sputum supernatant were measured by enzyme-linked immunosorbent assay (ELISA) kit. The subjects were treated with budesonide/formoterol (160/4.5 µg) one inhalation twice daily and re-examined after 1 month. RESULTS: Prior to treatment, there were no differences between the asthma and control groups in the levels of LL-37 in plasma and sputum supernatant (P = 0.427,0.427). The plasma concentrations of LL-37 in asthma group were negatively correlated with baseline forced expiratory volume in one second (FEV(1), r = -0.470, P = 0.005), percent predicted of FEV(1) (FEV(1)%pred, r = -0.421, P = 0.013) and forced vital capacity (FVC, r = -0.367, P = 0.033). After treatment, the plasma and sputum supernatant concentrations of LL-37 (M (Q(R))) in the asthma group (5.6 (16.2), 65.6 (184.0) µg/L) were significantly higher than those baseline concentrations (5.03 (9.21), 28.40(109.76) µg/L, P = 0.005, 0.015). In the eosinophilic asthma subgroup, the plasma and sputum supernatant concentrations of LL-37 (M (Q(R))) after treatment (5.3 (19.3), 65.6 (185.2) µg/L) were significantly higher than those baseline concentrations (6.7 (8.9) L, 35.3 (102.0) µg/L, P = 0.021,0.014). And in the non-eosinophilic asthma subgroup, the changes of plasma and sputum supernatant concentrations of LL-37 showed no significant differences (P = 0.139, 0.386). In the asthma group, the correlations between plasma concentrations of LL-37 and FEV(1), FEV(1)%pred, FVC were not statistically significant (P = 0.283, 0.706,0.272) after treatment. CONCLUSIONS: LL-37 may participate in the aggravation of asthma. The elevated concentrations of LL-37 in eosinophilic asthma is probably due to the resolved suppression of LL-37 expression by eosinophilic inflammation. But its mechanism needs further researches.

[Investigation of the level of perceived control of asthma and the factors affecting such perception in South China].

OBJECTIVE: To investigate the level of the patients perceived control of asthma (PCA) in South China and analyze the risk factors contributing to inadequate PCA. METHODS: A total of 150 asthmatic out-patients consisting of 86 males and 64 females aged 19-65 (38.6∓11.7) years were enrolled in this investigation. The patients were asked to complete questionnaires of the demographic data, perceived control of asthma (PCAQ-6) scales, asthma control test (ACT) scales and Standard asthma-specific quality of life [AQLQ(S)] scale. The data of spirometric measurements, blood cell count and induced sputum cell count were also collected. RESULTS: All the 150 asthmatic out-patients recruited completed the questionnaires and examinations. The PCAQ-6 scores ranged from 10 to 26 (18.75∓3.42) in these patients (18.6∓3.28 in male and 18.95∓3.6 in female patients), significantly lower than those reported in other countries (P<1). PCA was positively correlated to the level of asthma control (r(p)=0.377, P=0.000) and AQLQ(S) scores (r(p)=0.675, P=0.000). Multiple linear regression showed that PCA was positively correlated to FEV1% and blood neutrophil counts, and inversely to asthma duration. CONCLUSION: The level of the PCA appears inadequate in South China. The PCA can affect the level of asthma control and asthma-specific quality of life. The factors contributing to inadequate PCA include primarily asthma duration, lung function and blood neutrophil counts.

[Causal analysis of initial misdiagnosis of pulmonary embolism].

OBJECTIVE: To analyze the causes of initial erroneous diagnosis of pulmonary embolism (PE) to improve the diagnostic efficiency. METHODS: The clinical data of 63 patients with a definite diagnosis of PE were retrospectively analyzed. According to the initial diagnosis, the patients were divided into definite diagnosis group (Group A, 23 cases) and misdiagnosis group (group B, 40 cases). The risk factors, initial symptoms, time of definite diagnosis, Wells scores, revised Geneva scores, and findings in chest X-ray and ECGs after onset and before the definite diagnosis were compared between the two groups. RESULTS: In group A, recent operations, malignancy, long-term bedridden state, PE history and deep vein thrombosis (DVT) symptom were more commonly seen than in group B, and the patients in group B were more likely to have hypertension, smoking, diabetes mellitus and lower limb varicose veins. The patients in group B had significantly lower Wells scores and revised Geneva scores than those in group A [2.50 (5.00) vs 6.00 (6.00), u=-3.296, P<0.001; 5.50 (4.75) vs 12.00 (9.00), u=-3.187, P<0.001, respectively]. In group B, chest examination in 22 of the 40 cases (55%) reported pulmonary infection, and among them, 15 were misdiagnosed as pneumonia. In groups A and B, SIQIIITIII/QIIITIII in ECG was found in 5 (21.7%) and 0 cases (0%), and normal ECG in 2 (8.7%) and 18 (45.0%) cases, respectively, showing significant difference between the two groups (P=0.010 and 0.003, respectively). CONCLUSION: The initial misdiagnosis of PE results mainly from the low awareness of some of the PE risk factors on the part of the physicians, atypical clinical manifestations and excessive dependence on chest films and ECGs.