[Annual updates of pulmonary infectious diseases in 2023].

In 2023, a range of pulmonary infectious diseases remain a significant public health concern. Meanwhile, the growing problem of antibiotic resistance, rising tuberculosis cases with lagging control measures, and increased susceptibility to fungal pneumonia after viral infections, have complicated the diagnosis and treatment of respiratory infectious diseases. Despite these challenges, the year saw several significant research achievements in this field. Key advances include a deeper understanding of disease pathogenesis, improvements in pathogen detection technologies, the development of innovative antiviral and antibacterial drugs, progress in vaccine research, and advances in pulmonary rehabilitation methods. This review provided a concise summary of these key findings in 2023, with the aim of providing insights for future research and healthcare initiatives.

[Advances in the diagnosis and treatment strategy of polymyxin resistant Klebsiella pneumoniae].

In recent years, the detection rate of multidrug-resistant and pandrug-resistant Klebsiella pneumoniae has increased year on year, so polymyxin has received increasing attention as an antibiotic that is still sensitive to most of the multidrug-resistant strains. However, widespread use of polymyxin is likely to lead to the emergence of polymyxin-resistant Klebsiella pneumoniae. At the same time, the polymyxin hetero-resistance has made clinical prevention and treatment difficult. In addition to relying on the combination of polymyxins with other antibiotics, the search for new antibacterial drugs has also become a research hotspot. Research into early detection methods for polymyxin resistance can also help to optimize and improve the diagnosis and treatment strategies. This article reviewed the epidemic status, mechanism, detection methods and prevention measures of polymyxin-resistant Klebsiella pneumoniae.

Intravenous N-acetylcysteine in respiratory disease with abnormal mucus secretion.

OBJECTIVE: Evidence for the mucolytic and expectorant efficacy of intravenous (IV) N-acetylcysteine (NAC) is limited. This study aimed to evaluate in a large, multicenter, randomized, controlled, subject, and rater-blinded study whether IV NAC is superior to placebo and non-inferior to ambroxol in improving sputum viscosity and expectoration difficulty. PATIENTS AND METHODS: A total of 333 hospitalized subjects from 28 centers in China with respiratory disease (such as acute bronchitis, chronic bronchitis and exacerbations, emphysema, mucoviscidosis, and bronchiectasis) and abnormal mucus secretion were randomly allocated in a 1:1:1 ratio to receive NAC 600 mg, ambroxol hydrochloride 30 mg, or placebo as an IV infusion twice daily for 7 days. Mucolytic and expectorant efficacy was assessed by ordinal categorical 4-point scales and analyzed by stratified and modified Mann-Whitney U statistics. RESULTS: NAC showed consistent and statistically significant superiority to placebo and non-inferiority to ambroxol in change from baseline to day 7 in both sputum viscosity scores [mean (SD) difference 0.24 (0.763), p<0.001 vs. placebo] and expectoration difficulty score [mean (SD) difference 0.29 (0.783), p=0.002 vs. placebo]. Safety findings confirm the good tolerability profile of IV NAC reported from previous small studies, and no new safety concerns were identified. CONCLUSIONS: This is the first large, robust study of the efficacy of IV NAC in respiratory diseases with abnormal mucus secretion. It provides new evidence for IV NAC administration in this indication in clinical situations where the IV route is preferred.

[Annual update of pulmonary infectious diseases in 2022].

In 2022, coronavirus disease 2019 (COVID-19) remains rampant across the world. Several remarkable studies concerning pulmonary infectious diseases have been published during this pandemic. This review summarized the representative academic and translational medical progress over the past year (from October 1, 2021, to September 30, 2022), including COVID-19, community/hospital-acquired pneumonia, tuberculosis, and other respiratory viral infections.

[Update on COVID-19 in 2021].

The novel coronavirus disease 2019(COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has developed into a pandemic. SARS-CoV-2 is highly contagious, and is associated with high mortality. Some SARS-CoV-2 mutants are reported to be highly transmissible and pathogenic, and even have the potential to escape immune response. Distinct immune signatures exist between symptomatic and asymptomatic COVID-19 patients. Clinical characteristics of COVID-19 patients vary by age group. Currently, there are no proven effective therapeutics for COVID-19 and therefore controlling the spread of COVID-19 relies on the inoculation of vaccines, such as nucleic vaccines, inactivated vaccines, viral vector vaccines and protein vaccines. Here we summarized the progresses on the variants, clinical characteristics, treatments and vaccines for COVID-19.

[Development of multiple organ dysfunction syndrome in patients with Coronavirus Disease 2019: clinical characteristics and risk factors].

Objective: To explore the clinical characteristics and risk factors of patients with Coronavirus Disease 2019 (COVID-19) when developing multiple organ dysfunction syndrome (MODS). Methods: Data from 458 inpatients of confirmed COVID-19 in Wuhan, Shanghai and Tongling from December 29, 2019 to March 24, 2020 were retrospectively collected. COVID-19 was confirmed by real-time RT-PCR of throat swab samples. Data of demographics, clinical presentation, laboratory tests, imaging findings, treatment and prognosis were obtained from medical record and compared between COVID-19 patients with and without MODS. Risk factors for the development of MODS were analyzed by univariate and multivariate logistic regression analysis. Results: Of the 458 COVID-19 patients (266 from Wuhan, 208 from Shanghai, and 24 from Tongling), 103 developed transient or persistent MODS in the course. More male patients were found in those with MODS (72.8% vs 54.6%, P=0.001). And MODS patients were of older age (72.8% vs 54.6%, P=0.001), more chronic comorbidities (68.0% vs 43.4%, P<0.001), and longer onset-to-admission interval (9.0 vs 7.0 d, P<0.001). In addition, patients with MODS had more expectoration (45.6% vs 29.9%, P=0.003) and shortness of breath (52.4% vs 19.4%, P<0.001), dysfunction of various systems, decreased cellular immunity and elevated IL-6 (9.6 vs 7.6 g/L, P=0.015) in laboratory tests, isolation of other pathogens (18.4% vs 5.6%, P<0.001), and infiltration of all five lobes (75.3% vs 57.6%, P=0.003). During hospitalization, patients with MODS needed a higher proportion of comprehensive treatment and reached a mortality rate of 66.0%. Independents risk factors for development of MODS in COVID-19 patients were: onset-to-admission interval>7 days (OR=2.17, 95%CI: 1.11-4.22, P=0.023), shortness of breath (OR=3.19, 95%CI: 1.60-6.37, P=0.001), lymphocyte count<1×109/L (OR=2.67, 95%CI: 1.31-5.46, P=0.007), blood urea nitrogen>7mol/L (OR=6.27, 95%CI: 2.80-14.08, P<0.001), procalcitonin>0.1 ng/mL (OR=2.48, 95%CI: 1.20-5.13, P=0.014), and C-reactive protein>10 mg/L (OR=3.92, 95%CI: 1.41-10.89, P=0.009). Conclusions: COVID-19 patients with MODS were of higher severity and mortality. Early identification of high-risk groups with MODS according to risk factors may be helpful for early treatment.

[Venous thromboembolism risk and prophylaxis status of cancer inpatient].

Objective: To determine the risk profile of venous thromboembolism (VTE) and evaluate VTE prophylaxis implementation of the hospitalized cancer patients in the DissolVE 2 study. Methods: The data of hospitalized cancer patients in the DissolVE 2 study were analyzed. The risk distribution of VTE, preventive measures and in-hospital VTE events of hospitalized patients with tumors were described by percentage and 95% confident interval (CI). Results: A total of 1 535 cancer patients were included. According to the Padua score, 826 (53.8%) patients were at low risk of VTE, while 709 (46.2%) patients were at high VTE risk. VTE events occurred in 4 low-risk patients (0.5%; 95%CI: 0.1%, 1.2%) and 5 high-risk patients (0.7%; 95%CI: 0.2%, 1.6%). The overall incidence was 0.6% (9/1 535, 95%CI: 0.3%, 1.1%). Among patients with high VTE risk, 666 (93.9%) did not receive any VTE prophylaxis, and only 11 (1.6%) patients received appropriate VTE prophylaxis. Among patients who received VTE prevention, no VTE event was observed. Conclusions: Nearly half of the hospitalized cancer patients are at high risk of VTE, but most of them don't receive VTE prophylaxis. The results reflect the insufficient management of VTE risk for hospitalized cancer patients in China, and improvement of awareness and practice of VTE prophylaxis is urgently needed.

[A prospective multi-center clinical investigation of HIV-negative pulmonary cryptococcosis in China].

Objective: To investigate the current status of the diagnosis and treatment of pulmonary cryptococcosis in respiratory medicine and improve the understanding of the clinical characteristics of HIV-negative pulmonary cryptococcosis in China. Methods: A prospective multi-center open cohort study was designed to screen for pulmonary cryptococcosis in the general wards and intensive care units of the Department of Respiratory Diseases in 22 hospitals. The HIV-negative patients with positive cryptococcal etiological diagnosis based on smear culture, antigen detection and histopathology were enrolled in the study. The clinical data of enrolled patients were collected and analyzed. Results: A total of 457 cases of pulmonary cryptococcosis were enrolled, among which 3.28% (15/457) were disseminated infections. The case fatality rate was 0.88% (4/457). The majority of the cases were diagnosed by histopathological examinations (74.40%, 340/457) and cryptococcus antigen detection (37.64%, 172/457). Patients with pulmonary cryptococcosis accounted for 2.04‰ (457/223 748) of the total hospitalized patients in the Department of Respiratory Diseases during the same period, and the ratio was the highest in south and east China. Meanwhile, 70.24% (321/457) of the patients had no underlying diseases, while 87.75% (401/457) were found to have immunocompetent status. Cough and expectoration were the most common clinical symptoms in patients with pulmonary cryptococcosis. However, 25.16% (115/457) of the patients had no clinical symptom or physical signs. In terms of imaging features on pulmonary CT, multiple pulmonary lesions were more common than isolated lesions, and there were more subpleural lesions than perihilar or medial lesions. Morphologically, most of the lesions were middle-sized nodules (1-5 cm) or small-sized nodules (3 mm to 1 cm). The sensitivity of serum cryptococcus antigen test was 71.99% (203/282). Moreover, antigen-positive patients differed from antigen-negative patients in terms of basic immune status, clinical symptoms, imaging features and infection types. Meanwhile, immunocompromised patients differed from immunocompetent patients in terms of clinical symptoms, physical signs, infection-related inflammation indicator levels, imaging features, serum cryptococcus antigen positive rate and prognosis. Conclusions: The majority of cases of HIV-negative pulmonary cryptococcosis in China had no underlying disease or immunocompromised status, and the overrall prognosis was favorable. However, early diagnosis of HIV-negative pulmonary cryptococcosis remains challenging due to the complicated manifestations of the disease.

[Effect of adipose-derived mesenchymal stem cells and liraglutide on acute lung injury].

Objective: To explore the protective effect of human adipose-derived mesenchymal stem cells (AD-MSCs) and liraglutide on lipopolysaccharide (LPS) -induced acute lung injury (ALI) . Methods: AD-MSCs were cultured in vitro and randomly divided into 3 groups: control group, LPS group (30 mg/L) , and LPS (30 mg/L) +liraglutide (10 nM) group. MTT assay was used to detect the proliferation of AD-MSCs at 6, 24, 48 and 72 h. Annexin V-FITC / PI double staining flow cytometry was used to detect the apoptosis of the cells. Western blot was used to detect the expression of apoptotic proteins cleaved caspase-3, Bax and Bcl-2 at 72 h in vitro. For the in vivo experiment, 60 male SPF BALB/c mice were randomly divided into 5 groups: control group, ALI group, ALI+AD-MSCs group, ALI+Liraglutide group, and ALI+AD-MSCs+Lraglutide group. The mice were sacrificed on day 2 and day 7 after LPS treatment. HE staining was used to examine the pathological changes of the lungs of mice, and the scores of lung injury were measured. The lung tissues of mice were examined by immunohistochemistry, and the expression of the marker protein Nanog of mesenchymal stem cells was observed. BALF was collected, and the number of BALF neutrophils was counted by Rayleigh Giemsa staining. The wet/dry specific gravity of mouse lung tissue was recorded. Results: The apoptosis of AD-MSCs stimulated by LPS was significantly higher than that of the control group (P<0.05) , and the proliferation of AD-MSCs at 6, 24, 48 and 72 h was significantly lower than that of the control group (all P<0.05) . The addition of Liraglutide reduced the apoptosis of AD-MSCs (P<0.05) , and promoted the proliferation of AD-MSC at 6, 24, 48 and 72 h. Compared with the control group, in the 2 d and 7 d model groups, the lung injury pathology of ALI group had lung injury, increased number of neutrophils in BALF (65.63±1.34 vs 1.74±0.17, 51.67±1.35 vs 1.55±0.13) ×10(4)/ml (all P<0.05) , and increased W/D of lung tissues. The expression level of Nanog protein was low in the 7 d model group. Compared with the ALI group, in 2 d and 7 d model groups, the ALI+AD-MSCs group, the ALI+liraglutide group, and the ALI+AD-MSCs+liraglutide group showed reduced lung injury pathology, and the number of neutrophils was decreased, (37.04±1.23, 29.17±0.68) ×10(4) / ml (all P<0.05) in the ALI+AD -MSCs group, (39.58±1.67, 35.42±0.25) ×10(4) / ml in the ALI+Liraglutide group (all P<0.05) and (28.54±0.37, 21.46±0.89) ×10(4)/ml (all P<0.05) in the ALI+AD-MSCs+Liraglutide group. Lung tissue W/D in the ALI+AD-MSCs group, ALI+Liraglutide group and ALI+AD-MSCs+Liraglutide group showed the same trend. Nanog protein expression increased in the 7 d model group. Conclusions: AD-MSCs play a protective role in acute lung injury in mice under the synergistic effect of liraglutide.

[Current status of diagnosis and treatment of community-acquired pneumonia in Shanghai revealed by a questionnaire analysis].

Objective: To understand the current status of diagnosis and treatment of community-acquired pneumonia (CAP) among doctors in various hospitals across Shanghai, for the purpose of promoting the 2016 clinical practice guidelines for adult CAP of China. Methods: A questionnaire was designed to address the common questions in CAP management. The responses were collected via WeChat and the data were analyzed. Results: A total of 1 254 valid questionnaires were received, 46.1% from tertiary , 26.4% from secondary and 27.5% from primary care hospitals. Of these valid respondents, 31.4% were respiratory physicians and 68.6% from non-respiratory physicians. When diagnosing CAP, 78.1% of the doctors would use chest CT in more than 50% of the patients. Regarding the tools for evaluating the severity of CAP, 60.3% of the respondents would prefer CURB-65. "Respiratory failure requiring mechanical ventilation and septic shock" were the most common criteria for admission to ICU. Blood culture was not widely used in severe CAP regardless of the level of hospitals (P>0.05). The results of this survey showed that the top 5 pathogenic microorganisms of CAP were Streptococcus pneumoniae, Mycoplasma pneumoniae, Klebsiella pneumoniae, Haemophilus influenza and Chlamydia pneumoniae. For non-severe CAP patients, all the doctors tended to select monotherapy. The most frequently used antimicrobial regimen for severe CAP was third- or fourth-generation cephalosporin monotherapy. As for combination therapy, the most frequently used regimen in tertiary hospitals was "carbapenem plus vancomycin" , while in primary and secondary hospitals it was "ß-lactams plus macrolides" . More doctors from primary hospitals and non-respiratory medicine would consider "complete resolution of pulmonary opacity" as the indication to discontinue antimicrobial therapy or to discharge patients, and "prolonged high fever" , "large area consolidation" , "multiple lobe-segment involvement " as the indication for corticosteroid therapy. A significantly lower proportion of doctors in secondary and tertiary hospitals would recommend patients to receive vaccination than in primary hospitals (P<0.05). Conclusions: This questionnaire study showed that there was a gap between the ideal and the real world practice in CAP management. Efforts should be made to popularize the 2016 CAP guideline in hospitals of any level of care, especially primary hospitals, for the purpose of further standardizing CAP management in China.