Heterozygous CARD9 mutation favors the development of allergic bronchopulmonary aspergillosis / 中华医学杂志(英文版)

BACKGROUND@#Previous research demonstrated that a homozygous mutation of g.136372044G>A (S12N) in caspase recruitment domain family member 9 ( CARD9 ) is critical for producing Aspergillus fumigatus -induced ( Af -induced) T helper 2 (T H 2)-mediated responses in allergic bronchopulmonary aspergillosis (ABPA). However, it remains unclear whether the CARD9S12N mutation, especially the heterozygous occurrence, predisposes the host to ABPA.@*METHODS@#A total of 61 ABPA patients and 264 controls (including 156 healthy controls and 108 asthma patients) were recruited for sequencing the CARD9 locus to clarify whether patients with this heterozygous single-nucleotide polymorphisms are predisposed to the development of ABPA. A series of in vivo and in vitro experiments, such as quantitative real-time polymerase chain reaction, flow cytometry, and RNA isolation and quantification, were used to illuminate the involved mechanism of the disease.@*RESULTS@#The presence of the p.S12N mutation was associated with a significant risk of ABPA in ABPA patients when compared with healthy controls and asthma patients, regardless of Aspergillus sensitivity. Relative to healthy controls without relevant allergies, the mutation of p.S12N was associated with a significant risk of ABPA (OR: 2.69 and 4.17 for GA and AA genotypes, P = 0.003 and 0.029, respectively). Compared with patients with asthma, ABPA patients had a significantly higher heterozygous mutation (GA genotype), indicating that p.S12N might be a significant ABPA-susceptibility locus ( aspergillus sensitized asthma: OR: 3.02, P = 0.009; aspergillus unsensitized asthma: OR: 2.94, P = 0.005). The mutant allele was preferentially expressed in ABPA patients with heterozygous CARD9S12N , which contributes to its functional alterations to facilitate Af -induced T H 2-mediated ABPA development. In terms of mechanism, Card9 wild-type ( Card9WT ) expression levels decreased significantly due to Af -induced decay of its messenger RNA compared to the heterozygous Card9S12N . In addition, ABPA patients with heterozygous CARD9S12N had increased Af -induced interleukin-5 production.@*CONCLUSION@#Our study provides the genetic evidence showing that the heterozygous mutation of CARD9S12N , followed by allele expression imbalance of CARD9S12N , facilitates the development of ABPA.

A survey of awareness and knowledge about influenza and vaccination among primary care providers in Shanghai / 中华全科医师杂志

Objective:To investigate the awareness and knowledge of influenza and vaccine among primary care providers in Shanghai.Methods:An online questionnaires survey was conducted by Shanghai Alliance for Respiratory Diseases in Primary Care from December 2017 to August 2018, healthcare providers in district central hospitals and community health care centers of Shanghai were invited to participate in the survey. The questionnaire contained the following items: the basic information of respondents; knowledge of influenza and its vaccine; current status of influenza vaccination; factors affecting promoting vaccination; the intention, attitude, perception of promoting vaccination and the influencing factors, and suggestions on promoting influenza vaccination.Results:A total of 1 542 valid questionnaires were collected, 88.3% (1 361/1 542) responders correctly recognized main symptoms of influenza; 58.2% (898/1 542) ignored the contact transmission of influenza; 41.6% (641/1 542) didn′t know the frequency of influenza vaccination; 82.7% (1 276/1 542) failed to recognize that pregnant women should also receive influenza vaccination. The survey showed that 31.2% (481/1 542) of responders had been vaccinated against influenza. The vaccination rate in community health care institutions was significantly higher than that in district central hospitals [39.1% (304/778) vs. 23.2% (177/764), χ 2=45.44, P<0.05]. Factors affecting vaccination for healthcare providers were: influenza antigen was variable, and vaccination had no effects [49.5% (404/816)]; the efficacy of the flu vaccine was doubt [48.8% (634/1 298)]; the vaccine wasn′t free [46.5%(604/1 298)]. The respondents believed that the main ways to improve the influenza vaccination were to formulate relevant national vaccination policies [79.7%(1 229/1 542)], to regularly publicize knowledge of influenza and influenza vaccine to residents through communities [65.8% (1 015/1 542)], and to recommend the patients by primary care medical staff [64.4% (993/1 542)]. Conclusion:Many healthcare providers have insufficient knowledge about influenza and vaccine. The vaccination rate of community health institutions is higher than that in district central hospitals in Shanghai. The willingness to promote influenza vaccination can be influenced by some factors. Increasing the willingness of healthcare providers might be helpful to improve the vaccination coverage among residents in the community.

Efficacy of add-on montelukast in nonasthmatic eosinophilic bronchitis: the additive effect on airway inflammation, cough and life quality / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The efficacy of montelukast (MONT), a cysteinyl leukotriene receptor antagonist, in nonasthmatic eosinophilic bronchitis (NAEB), especially its influence on cough associated life quality is still indefinite. We evaluated the efficacy of MONT combined with budesonide (BUD) as compared to BUD monotherapy in improving life quality, suppressing airway eosinophilia and cough remission in NAEB.</p><p><b>METHODS</b>A prospective, open-labeled, multicenter, randomized controlled trial was conducted. Patients with NAEB (aged 18-75 years) were randomized to inhaled BUD (200 μg, bid) or BUD plus oral MONT (10 μg, qn) for 4 weeks. Leicester cough questionnaire (LCQ) life quality scores, cough visual analog scale (CVAS) scores, eosinophil differential ratio (Eos), and eosinophil cationic protein (ECP) in induced sputum were monitored and compared.</p><p><b>RESULTS</b>The control and MONT groups contained 33 and 32 patients, respectively, with similar baseline characteristics. Significant with-in group improvement in CVAS, LCQ scores, Eos, and ECP was observed in both groups during treatment. After 2-week treatment, add-on treatment of MONT was significantly more effective than BUD monotherapy for CVAS decrease and LCQ scores improvement (both P < 0.05). Similar results were seen at 4-week assessment (both P < 0.05). 4-week add-on therapy of MONT also resulted in a higher percentage of patients with normal sputum Eos (<2.5%) and greater decrease of ECP (both P < 0.05).</p><p><b>CONCLUSIONS</b>MONT combined with BUD was demonstrated cooperative effects in improvement of life quality, suppression of eosinophilic inflammation, and cough remission in patients with NAEB.</p>

Application of therapeutic drug monitoring of vancomycin / 中国感染与化疗杂志

Objective To analyze the relationship between plasma concentration and efficacy , adverse drug reactions by monitoring vancomycin serum concentrations for appropriately treating the infections caused by methicillin‐resistant Staphylococcus aureus or other gram‐positive cocci .Methods Vancomycin concentration was monitored in the patients with indications for vancomycin therapy .Blood sample was taken after vancomycin was administered for at least 4 doses .The blood sample collected within 30 minutes before dosing was used to determine the trough blood concentration .The samples were taken within 30 minutes to 1 hour after infusion of vancomycin were used to estimate the peak concentration by fluorescence polarization immunoassay .The clinical data were collected at the same time to analyze clinical efficacy and safety .Results Vancomycin trough concentration ranged from 3 .22 mg/L to 50 .79 mg/L in 25 patients ,specifically ,＜ 5 mg/L in 3 cases ,5‐＜10 mg/L in 11 cases ,10‐15 mg/L in 3 cases ,and > 15 mg/L in 8 csaes .Peak concentration ranged from 13 .57 mg/L to 60 .47 mg/L ,specifically ,＜ 25 mg/L in 14 cases ,25‐40 mg/L in 7 cases ,and > 40 mg/L in 4 cases .The infection was cured in 80 .0% (20/25) of the patients .The gram‐positive cocci were eradicated in 87 .5% (21/24) of the patients .The dosage of vancomycin was adjusted in 13 patients according to the results of blood concentration monitoring .Majority of these patients (12/13 ,92 .3% ) were cured .Renal impairment was observed in 4 patients .Conclusions Vancomycin is safe and effective in treatment of methicillin‐resistant Staphylococcus aureus and other gram‐positive bacterial infections . Vacomycin concentration varies from person to person . Serum concentration monitoring is required to achieve best outcomes and the goal of individualized treatment of vancomycin.

Effects of pulmonary rehabilitation on patients with stable chronic obstructive pulmonary disease / 中华物理医学与康复杂志

Objective To observe the effects of puhnonary rehabilitation on the symptoms and quality of life of persons with chronic obstructive pulmonary disease (COPD).Methods COPD patients were recruited from a hospital and community health centers and given pulmonary rehabilitation in the community.The rehabilitation program included health education and nutrition guidance,medication,breathing exercises,and physical exercise.Each patient was followed up every 4 weeks by telephone.The outcome measures included pulmonary function (FEV1％,FEV1/FVC％),St George's questionnaire (SGRQ),the Medical Research Council scale (MRC),Borg scoring,evaluation of anxiety and depression,the six-minute walk test (6MWT),and an evaluation of nutritional status.All of the patients were observed for one year.Results A total of 85 patients completed the program and were included in the final statistical analysis.There was no difference in FEV1 ％ before and after rehabilitation.Six-minute walking distance improved significantly in statistical terms but the average increase was only from (416.1 ±99.84)m to (437.51 ±116.17)m.The SGRQ scores decreased by an average of 4.8 points after a year of rehabilitation,with significant improvements among the moderately and severely impaired.Incidents of COPD exacerbation also decreased significantly.Patients with a low body mass index had the greatest SGRQ score improvments.Few patients showed depression or anxiety in this research population.Conclusions Pulmonary rehabilitation in the community can improve exercise tolerance and the quality of life for persons with COPD,reducing incidents of acute exacerbation.Patients may benefit from such pulmonary rehabilitation regardless of disease severity.The compliance was good despite the infrequent monitoring.Pulmonary rehabilitation in the community is worthy of more widespread use.