Limited information exists on the clinical characteristics predictive of mortality in patients aged ≥65 years in many countries. The impact of adherence to current antimicrobial guidelines on the mortality of hospitalized elderly patients with community-acquired pneumonia (CAP) has never been assessed.
Abstract Background The study was to evaluate initial antimicrobial regimen and clinical outcomes and to explore risk factors for clinical failure (CF) in elderly patients with community-acquired pneumonia (CAP). Methods 3011 hospitalized elderly patients were enrolled from 13 national teaching hospitals between January 1, 2014 and December 31, 2014 initiated by the CAP-China network. Risk factors for CF were screened by multivariable logistic regression analysis. Results The incidence of CF in elderly CAP patients was 13.1%. CF patients were older, longer hospital stays and higher treatment costs than clinical success (CS) patients. The CF patients were more prone to present hyperglycemia, hyponatremia, hypoproteinemia, pleural effusion, respiratory failure and cardiovascular events. Inappropriate initial antimicrobial regimens in CF group were significantly higher than CS group. Undertreatment, CURB-65, PH < 7.3, PaO 2 /FiO 2 < 200 mmHg, sodium < 130 mmol/L, healthcare-associated pneumonia, white blood cells > 10,000/mm 3 , pleural effusion and congestive heart failure were independent risk factors for CF in multivariable logistic regression analysis. Male and bronchiectasis were protective factors. Conclusions Discordant therapy was a cause of CF. Early accurate detection and management of prevention to potential causes is likely to improve clinical outcomes in elderly patients CAP. Trial registration A Retrospective Study on Hospitalized Patients With Community-acquired Pneumonia in China (CAP-China) (RSCAP-China), NCT02489578. Registered 16 March 2015, https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0005E5S&selectaction=Edit&uid=U0000GWC&ts=2&cx=1bnotb
The influenza A (H1N1) pdm09 virus remains a critical global health concern and causes high levels of morbidity and mortality. Severe acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the major outcomes among severely infected patients. Our previous study found that interleukin (IL)-17A production by humans or mice infected with influenza A (H1N1) pdm09 substantially contributes to ALI and subsequent morbidity and mortality. However, the cell types responsible for IL-17A production during the early stage of severe influenza A (H1N1) pdm09 infection remained unknown. In this study, a mouse model of severe influenza A (H1N1) pdm09 infection was established. Our results show that, in the lungs of infected mice, the percentage of γδT cells, but not the percentages of CD4+Th and CD8+Tc cells, gradually increased and peaked at 3 days post-infection (dpi). Further analysis revealed that the Vγ4+γδT subset, but not the Vγ1+γδT subset, was significantly increased among the γδT cells. At 3 dpi, the virus induced significant increases in IL-17A in the bronchoalveolar lavage fluid (BALF) and serum. IL-17A was predominantly secreted by γδT cells (especially the Vγ4+γδT subset), but not CD4+Th and CD8+Tc cells at the early stage of infection, and IL-1β and/or IL-23 were sufficient to induce IL-17A production by γδT cells. In addition to secreting IL-17A, γδT cells secreted interferon (IFN)-γ and expressed both an activation-associated molecule, natural killer group 2, member D (NKG2D), and an apoptosis-associated molecule, FasL. Depletion of γδT cells or the Vγ4+γδT subset significantly rescued the virus-induced weight loss and improved the survival rate by decreasing IL-17A secretion and reducing immunopathological injury. This study demonstrated that, by secreting IL-17A, lung Vγ4+γδT cells, at least, in part mediated influenza A (H1N1) pdm09-induced immunopathological injury. This mechanism might serve as a promising new target for the prevention and treatment of ALI induced by influenza A (H1N1) pdm09.
Abstract Background : The study was to evaluate initial antimicrobial regimen and clinical outcomes and to explore risk factors for clinical failure (CF) in elderly patients with community-acquired pneumonia (CAP). Methods : 3,011 hospitalized elderly patients were enrolled from 13 national teaching hospitals between January 1, 2014 and December 31, 2014 initiated by the CAP-China network. Risk factors for CF were screened by multivariable logistic regression analysis. Results : The incidence of CF in elderly CAP patients was 13.1%. CF patients were older, longer hospital stays and higher treatment costs than clinical success (CS) patients. The CF patients were more prone to present hyperglycemia, hyponatremia, hypoproteinemia, pleural effusion, respiratory failure and cardiovascular events. Inappropriate initial antimicrobial regimens in CF group were significantly higher than CS group. Undertreatment, CURB-65, PH<7.3, PaO 2 /FiO 2 < 200 mmHg, sodium <130 mmol/L, healthcare-associated pneumonia, white blood cells >10000/mm 3 , pleural effusion and congestive heart failure were independent risk factors for CF in multivariable logistic regression analysis. Male and bronchiectasis were protective factors. Conclusions : Discordant therapy was a cause of CF. Early accurate detection and management of prevention to potential causes is likely to improve clinical outcomes in elderly patients CAP. Trial registration : A Retrospective Study on Hospitalized Patients With Community-acquired Pneumonia in China (CAP-China) (RSCAP-China), NCT02489578. Registered 16 March 2015, https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0005E5S&selectaction=Edit&uid=U0000GWC&ts=2&cx=1bnotb
Objectives To describe the clinical characteristics and management of patients hospitalised with community-acquired pneumonia (CAP) in China. Design This was a multicentre, retrospective, observational study. Setting 13 teaching hospitals in northern, central and southern China from 1 January 2014 to 31 December 2014 Participants Information on hospitalised patients aged ≥14 years with radiographically confirmed pneumonia with illness onset in the community was collected using standard case report forms. Primary and secondary outcome measures Resource use for CAP management. Results Of 14 793 patients screened, 5828 with radiographically confirmed CAP were included in the final analysis. Low mortality risk patients with a CURB-65 score 0–1 and Pneumonia Severity Index risk class I–II accounted for 81.2% (4434/5594) and 56.4% (2034/3609) patients, respectively. 21.7% (1111/5130) patients had already achieved clinical stability on admission. A definite or probable pathogen was identified only in 12.7% (738/5828) patients. 40.9% (1575/3852) patients without pseudomonal infection risk factors received antimicrobial overtreatment regimens. The median duration between clinical stability to discharge was 5.0 days with 30-day mortality of 4.2%. Conclusions These data demonstrated the overuse of health resources in CAP management, indicating that there is potential for improvement and substantial savings to healthcare systems in China. Trial registration number NCT02489578 ; Results.
The detailed features and the longitudinal variation of influenza-specific T cell responses within naturally infected patients and the relationship with disease severity remain uncertain. In this study, we characterized the longitudinal influenza-specific CD4+ and CD8+ T cell responses, T cell activation, and migration-related cytokine/chemokine secretion in pH1N1-infected patients with or without viral pneumonia with human PBMCs. Both the influenza-specific CD4+ and CD8+ T cells presented higher responses in patients with severe infection than in mild ones, but with distinct longitudinal variations, phenotypes of memory markers, and immune checkpoints. At 7 ± 3 d after onset of illness, effector CD8+ T cells (CD45RA+CCR7-) with high expression of inhibitory immune receptor CD200R dominated the specific T cell responses. However, at 21 ± 3 d after onset of illness, effector memory CD4+ T cells (CD45RA-CCR7-) with high expression of PD1, CTLA4, and LAG3 were higher among the patients with severe disease. The specific T cell magnitude, T cell activation, and migration-related cytokines/chemokines possessed a strong connection with disease severity. Our findings illuminate the distinct characteristics of immune system activation during dynamic disease phases and its correlation with lung injury of pH1N1 patients.
The effect of corticosteroids on influenza A(H1N1)pdm09 viral pneumonia patients remains controversial, and the impact of dosage has never been studied.Using data of hospitalized adolescent and adult patients with influenza A(H1N1)pdm09 viral pneumonia, prospectively collected from 407 hospitals in mainland China, the effects of low-to-moderate-dose (25-150 mg d-1 ) and high-dose (>150 mg d-1 ) corticosteroids on 30-day mortality, 60-day mortality, and nosocomial infection were assessed with multivariate Cox regression and propensity score-matched case-control analysis.In total, 2141 patients (median age: 34 years; morality rate: 15.9%) were included. Among them, 1160 (54.2%) had PaO2 /FiO2 <300 mm Hg on admission, and 1055 (49.3%) received corticosteroids therapy. Corticosteroids, without consideration of dose, did not influence either 30-day or 60-day mortality. Further analysis revealed that, as compared with the no-corticosteroid group, low-to-moderate-dose corticosteroids were related to reduced 30-day mortality (adjusted hazard ratio [aHR] 0.64 [95% CI 0.43-0.96, P=.033]). In the subgroup analysis among patients with PaO2 /FiO2 <300 mm Hg, low-to-moderate-dose corticosteroid treatment significantly reduced both 30-day mortality (aHR 0.49 [95% CI 0.32-0.77]) and 60-day mortality (aHR 0.51 [95% CI 0.33-0.78]), while high-dose corticosteroid therapy yielded no difference. For patients with PaO2 /FiO2 ≥300 mm Hg, corticosteroids (irrespective of dose) showed no benefit and even increased 60-day mortality (aHR 3.02 [95% CI 1.06-8.58]). Results were similar in the propensity model analysis.Low-to-moderate-dose corticosteroids might reduce mortality of influenza A(H1N1)pdm09 viral pneumonia patients with PaO2 /FiO2 <300 mm Hg. Mild patients with PaO2 /FiO2 ≥300 mm Hg could not benefit from corticosteroid therapy.
To the Editor: With an aging global population, the incidences of community-acquired pneumonia (CAP) and chronic obstructive pulmonary disease (COPD) have significantly increased.[1] Previous studies have confirmed that COPD and asthma are independently associated with the prevalence of CAP. The use of inhaled corticosteroid (ICS), the cornerstone of treatment for asthma, COPD with frequent acute exacerbations, and asthma-COPD overlap (ACO) may induce changes in the local lung microbiome and abnormal lung immunity, ultimately, causing a significantly increased risk of pneumonia. However, in cases of pneumonia, the effect of the use of ICS on CAP mortality remains controversial. While data from one study favored the prior use of ICS, which was associated with a significantly lower short-term mortality rate,[2] other studies have identified no impact on mortality. To date, data on the impact of the use of ICS on mortality, prehospitalization or during hospitalization, are scarce, particularly in the older population. Therefore, this multicenter, retrospective study explored the association between the use of ICS during hospitalization and short-term mortality in older patients with CAP and those with chronic pulmonary disease (CPD). A multicenter, retrospective study on hospitalized patients with CAP aged ≥65 years from the CAP-China network, between January 1, 2014, and December 31, 2014, was conducted (details are available in a study by Han et al[1]). The present study was approved by the Human Subject Protection Program Institutional Review Board of China-Japan Friendship Hospital (No. 2015-85). Additional approval was obtained from the local institutional review boards of each participating hospital. The requirement for patient consent was waived owing to the retrospective and observational study design. This study had been registed on Clinicaltrials.gov (https://register.clinicaltrials.gov/prs/app/template/Home.vm?ts=4&cx=-cnls5z) with the number of NCT02489578. CPD was defined as the presence of asthma, COPD, or ACO. ACO was characterized by persistent airflow limitation with several features typically associated with asthma and COPD. ICS exposure was defined as the use of fluticasone, budesonide, or beclomethasone alone or in combination with β-receptor agonists and/or adrenergic receptor blockers through dry powder inhalers, atomized inhalation metered-dose inhalers, or aerosol inhalation during hospitalization. Categorical variables are presented as frequencies or percentages, and continuous variables are presented as mean ± standard deviation. The χ2 test or Fisher's exact tests with Boferroni method was used for categorical variables, and the analysis of variance test for continuous variables with least significant difference (LSD) method for pairwise comparisons. Patients were divided into the following groups: without CPD, COPD, asthma, and ACO groups. We performed 1:1 propensity score matching (PSM) without replacement to match participants within a predefined propensity score radius (caliper width of 0.1) among patients with and without the use of ICS. The following covariates were matched: age, sex, hypertension, congestive heart failure, cerebral vascular disease, and diabetes mellitus. Variables with P value less than 0.10 in univariate logistic analyses were included in a multivariate logistic regression analysis model for 30-day mortality in PSM patients and all COPD patients, and a stepwise forward model was used to select independent risk factors. The 95% confidence intervals (CIs) and levels of significance are reported. The cumulative survival curve for 30-day mortality was stratified according to the use of ICS during hospitalization. All data were analyzed using SPSS (version 20, IBM Corp., New York, USA); a value of P <0.05 was considered statistically significant. A total of 2437 patients with CAP aged ≥65 years were finally enrolled in the study. Among them, 1997 (81.9%), 355 (14.6%), 64 (2.6%), and 21 (0.9%) patients were classified into the without CPD, COPD, asthma, and ACO groups, respectively. The mean age of asthmatic patients with CAP was significantly lower than that of the patients in COPD group or without CPD group (P <0.001), as was the male proportion (asthma group vs. COPD group, χ2 = 15.554, P <0.001; asthma group vs. without CPD group, χ2 = 11.940, P = 0.001). The proportion of patients using ICS during hospitalization was significantly lower in patients without CPD than in those with CPD. No significant differences were identified in the pneumonia severity index scores, clinical stability on admission, intensive care unit (ICU) admission, mechanical ventilation, treatment failure, in-hospital mortality, 30-day mortality, or length of stay among the four groups [Supplementary Table 1, https://links.lww.com/CM9/B809]. After PSM, 384 pairs of older patients [SupplementaryTable 2, https://links.lww.com/CM9/B809] were included in the multivariate logistic analysis of 30-day mortality. Blood sodium level <130 mmol/L (odds ratio [OR] = 6.184; 95% CI: 1.821–20.993, P = 0.003), white blood cell count >10 × 109/L (OR = 4.975; 95% CI: 2.111–11.723, P <0.001), and the CURB-65 (confusion, uremia >7 mmol/L, respiratory rate ≥30/minutes, hypotension, and aged 65 years or older) score (OR = 2.973; 95% CI: 1.754–5.041, P <0.001) were independent risk factors for 30-day mortality, whereas use of ICS during hospitalization (OR = 0.408; 95% CI: 0.175–0.952, P = 0.038) was a protective factor [Supplementary Table 3, https://links.lww.com/CM9/B809]. The Kaplan–Meier (KM) curve demonstrated that older patients who used ICS during hospitalization in the matched cohort had significantly higher survival (χ2 = 5.460; P = 0.019) [Supplementary Figure 1A, https://links.lww.com/CM9/B809]. For the subgroup of patients with COPD (n = 376), the CURB-65 score (OR = 4.190; 95% CI: 1.684–10.427, P = 0.002), blood sodium level <130 mmol/L (OR = 5.779; 95% CI: 1.310–25.488, P = 0.021), and arterial oxygen saturation <90% (OR = 3.414; 95% CI: 1.033–11.284, P = 0.044) were independent risk factors for 30-day mortality, whereas use of ICS during hospitalization was not a protective factor (OR = 0.233; 95% CI: 0.048–1.119, P = 0.069) [Supplementary Table 4, https://links.lww.com/CM9/B809]. The KM curve indicated that use of ICS during hospitalization significantly reduced the 30-day mortality in the subgroup of patients with COPD (χ2 = 5.264; P = 0.022) [Supplementary Figure 1B, https://links.lww.com/CM9/B809]. This study aimed to evaluate the association between the use of ICS during hospitalization and short-term mortality in older CAP patients and those with CPD in China. We found that hyponatremia, leukocytosis, and the CURB-65 score were independent risk factors associated with 30-day mortality in matched 384 pairs of patients, whereas the use of ICS during hospitalization was a protective factor. The use of ICS during hospitalization in patients with COPD significantly decreased short-term mortality, but not independent risk factor. A meta-analysis of the effect of COPD on mortality in patients with CAP showed no associations between the presence of COPD and in-hospital or 30-day mortality in CAP patients (OR = 0.93, 95% CI: 0.60–1.45 and OR = 1.06, 95% CI: 0.72–1.58, respectively).[3] Moreover, a prospective study on 4079 patients with CAP over a 12-year period identified no significant differences in ICU admission, mechanical ventilation, and 30-day mortality among patients with or without asthma,[4] consistent with our results. In our study, the mortality rate of patients with CAP and ACO is low. The role of corticosteroids against the inflammatory response to infection in patients with CAP is debatable. Given the impact on clinical outcomes, patients with severe CAP may benefit from systemic corticosteroids. Some patients with CAP, even those without CPD, may experience wheezing, chest tightness, severe and frequent cough due to airway hyper-responsiveness, and airway mucus hypersecretion. Aerosol inhalation of ICS alone or that combined with β-receptor agonists and/or M-cholinergic receptor blockers may be appropriate for such patients. In our study, approximately one-third of the patients without CPD experienced wheezing or chest tightness, and 11.2% of these patients were prescribed ICS during hospitalization; and the proportion of the use of ICS was 33.3–37.5% in the patients with CPD. The KM curves in the current study indicate that the use of ICS during hospitalization significantly reduces 30-day mortality in the matched cohort and patients with COPD (P = 0.019 and 0.022, respectively). In addition, the use of ICS during hospitalization (OR = 0.408; 95% CI: 0.175–0.952, P = 0.038) was a protective factor in the matched cohort but not in the patients with COPD (OR = 0.233; 95% CI: 0.048–1.119, P = 0.069). A study analyzing the association of ICS exposure with mortality in 6353 older patients with CAP and COPD showed that prehospital use of ICS was significantly associated with lower 30-day mortality (adjusted OR = 0.76; 95% CI: 0.70–0.83), and the KM curve indicated that patients with ICS use had significantly higher survival over the first 90 days after admission.[2] Chen et al[5] also confirmed that the use of ICS decreased 30-day mortality in patients with CAP and COPD, generally concordant with our data. In the present study, hyponatremia, leukocytosis, and the CURB-65 score were independent risk factors for short-term mortality in older patients with CAP, consistent with previous observations. The incidence of hyponatremia was 8–31% in adult patients with CAP and was associated with increased mortality, more severe pulmonary inflammation with higher levels of leukocytes and C-reactive protein, more severe disease severity, more frequent ICU admission, and prolonged hospital stay. In patients with CAP and COPD, dyspnea occurred in 60.4% of cases. Data showed hypoxemia was associated with 30-day mortality in such population, consistent with the report from the Pneumonia Patient Outcomes Research Team cohort study. The present study had several limitations. First, data regarding prehospitalization use of ICS, ICS dose, duration of treatment, and combination with long-acting β-agonists and/or M-cholinergic receptor blockers were not systematically documented. Second, the diagnoses of COPD and asthma were self-reported, and data on lung function related to CPD were lacking. Therefore, the relationship between ICS and/or bronchodilators, lung function, and mortality could not be evaluated. Third, some bias may have been introduced owing to the partial loss of laboratory data when performing the statistical analysis. In conclusion, this study revealed that the use of ICS during hospitalization was associated with a significantly lower 30-day mortality in older patients with CAP. These findings provide new perspectives on the potential benefit of ICS use as an immunomodulatory therapy in older patients with CAP. Therefore, further multicenter prospective studies are warranted. Acknowledgments The authors are grateful for the contributions of all the staff of the CAP-China network for their help with data collection and input. Thanks to Yi Wang for revising the figures. Funding This work was supported by the National Science Grant for Distinguished Young Scholars (No. 81425001/H0104), the National Key Technology Support Program from the Ministry of Science and Technology (No. 2015BAI12B11), and the Beijing Science and Technology Project (No. D151100002115004). Conflicts of interest None.
Abstract Background: The study was to evaluate initial antimicrobial regimen and clinical outcomes and to explore risk factors for clinical failure (CF) in elderly patients with community-acquired pneumonia (CAP). Methods: 3,011 hospitalized elderly patients were enrolled from 13 national teaching hospitals between January 1, 2014 and December 31, 2014 initiated by the CAP-China network. Risk factors for CF were screened by multivariable logistic regression analysis. Results: The incidence of CF in elderly CAP patients was 13.1%. CF patients were older, longer hospital stays and higher treatment costs than clinical success (CS) patients. The CF patients were more prone to present hyperglycemia, hyponatremia, hypoproteinemia, pleural effusion, respiratory failure and cardiovascular events. Inappropriate initial antimicrobial regimens in CF group were significantly higher than CS group. Undertreatment, CURB-65, PH<7.3, PaO 2 /FiO 2 < 200 mmHg, sodium <130 mmol/L, healthcare-associated pneumonia, white blood cells >10000/mm 3 , pleural effusion and congestive heart failure were independent risk factors for CF in multivariable logistic regression analysis. Male and bronchiectasis were protective factors. Conclusions: Discordant therapy was a cause of CF. Early accurate detection and management of prevention to potential causes is likely to improve clinical outcomes in elderly patients CAP. Trial registration : A Retrospective Study on Hospitalized Patients With Community-acquired Pneumonia in China (CAP-China) (RSCAP-China), NCT02489578. Registered 16 March 2015, https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0005E5S&selectaction=Edit&uid=U0000GWC&ts=2&cx=1bnotb
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