Investigation of predictors for in-hospital death or long-term hospitalization in community-acquired pneumonia with risk factors for aspiration.

Background: It is known that the mortality of pneumonia in patients with risk factors for aspiration is worse than that in those without these risk factors. However, it is still unknown which risk factors for aspiration predict prognosis. Therefore, we aimed to determine which risk factors for aspiration are associated with death or prolonged hospitalization. Methods: We prospectively followed patients with community-acquired pneumonia at a single hospital providing acute to chronic care in Japan until they died or were discharged. Patients at any risk of aspiration were included. The associations between pneumonia severity, individual risk factors for aspiration, and in-hospital death or prolonged hospitalization were investigated. Overall survival was estimated by the Kaplan - Meier method, and the factors associated with in-hospital death or prolonged hospitalization were investigated by multivariate analysis using factors selected by a stepwise method. Results: In total, 765 patients with pneumonia and risk factors for aspiration were recruited. One hundred and ten patients deceased, and 259 patients were hospitalized over 27 days. In-hospital death increased as the number of risk factors for aspiration increased. In the multivariate analysis, male, impaired consciousness, acidemia, elevated blood urea nitrogen, and bedridden status before the onset of pneumonia were associated with in-hospital death (odds ratio [OR]: 2.5, 2.5, 3.6, 3.1, and 2.6; 95% confidence interval [CI]: 1.6-4.1, 1.4-4.2, 1.6-8.0, 1.9-5.0, and 1.6-4.2 respectively). In the Cox regression analysis, these factors were also associated with in-hospital death. None of the vital signs at admission were associated. Tachycardia, elevated blood urea nitrogen, hyponatremia, and bedridden status were associated with hospitalization for >27 days (OR: 4.1, 2.3, 4.3, and 2.9; 95% CI: 1.3-12.9, 1.5-3.4, 2.0-9.4, and 2.0-4.0, respectively). Conclusions: Blood sampling findings and bedridden status are useful for predicting in-hospital mortality and long-term hospitalization in patients with pneumonia and any risk factor for aspiration.

Clinical phenotypes of nontuberculous mycobacterial disease by cluster analysis based on pulmonary function.

BACKGROUND: Nontuberculous mycobacterial pulmonary disease (NTM-PD) often exhibits pulmonary function impairment, such as obstructive or restrictive pattern, with variation among patients according to the damaged lesions in the lung. METHODS: Patients with NTM-PD were consecutively enrolled between September 2019 and December 2020 at the Respiratory Infection Clinic of our hospital. Patients' data were comprehensively collected through laboratory examinations, PFT, chest computed tomography, and questionnaires for the assessment of subjective symptoms and health-related quality of life (HRQOL). Hierarchical cluster analysis was performed using PFT parameters to compare the clinical findings among clusters. RESULTS: Data of 104 patients were analyzed and classified into four clusters. The restrictive pattern with decreased forced expiratory volume in 1 s (FEV1) group showed high serum C-reactive protein and low albumin levels, severe radiological findings, and low HRQOL. In the restrictive pattern with preserved FEV1 group, HRQOL was as low as that in the restrictive pattern with decreased FEV1 group, and bacterial exacerbation was observed relatively frequently. HRQOL in the obstructive impairment group was maintained in comparison with that in the normal group. CONCLUSION: NTM-PD phenotypes were identified using cluster analysis based on PFT. Two different severe phenotypes were also observed. In the early stages of NTM-PD, PFT may be useful in recognizing disease progression.

Artificial intelligence-based analysis of the spatial distribution of abnormal computed tomography patterns in SARS-CoV-2 pneumonia: association with disease severity.

BACKGROUND: The substantial heterogeneity of clinical presentations in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia still requires robust chest computed tomography analysis to identify high-risk patients. While extension of ground-glass opacity and consolidation from peripheral to central lung fields on chest computed tomography (CT) might be associated with severely ill conditions, quantification of the central-peripheral distribution of ground glass opacity and consolidation in assessments of SARS-CoV-2 pneumonia remains unestablished. This study aimed to examine whether the central-peripheral distributions of ground glass opacity and consolidation were associated with severe outcomes in patients with SARS-CoV-2 pneumonia independent of the whole-lung extents of these abnormal shadows. METHODS: This multicenter retrospective cohort included hospitalized patients with SARS-CoV-2 pneumonia between January 2020 and August 2021. An artificial intelligence-based image analysis technology was used to segment abnormal shadows, including ground glass opacity and consolidation. The area ratio of ground glass opacity and consolidation to the whole lung (GGO%, CON%) and the ratio of ground glass opacity and consolidation areas in the central lungs to those in the peripheral lungs (GGO(C/P)) and (CON(C/P)) were automatically calculated. Severe outcome was defined as in-hospital death or requirement for endotracheal intubation. RESULTS: Of 512 enrolled patients, the severe outcome was observed in 77 patients. GGO% and CON% were higher in patients with severe outcomes than in those without. Multivariable logistic models showed that GGO(C/P), but not CON(C/P), was associated with the severe outcome independent of age, sex, comorbidities, GGO%, and CON%. CONCLUSION: In addition to GGO% and CON% in the whole lung, the higher the ratio of ground glass opacity in the central regions to that in the peripheral regions was, the more severe the outcomes in patients with SARS-CoV-2 pneumonia were. The proposed method might be useful to reproducibly quantify the extension of ground glass opacity from peripheral to central lungs and to estimate prognosis.

Impact of wearing a surgical facemask during exercise on dyspnea in patients with chronic pulmonary infections: A randomized crossover study.

BACKGROUND: Wearing facemasks in public is effective in preventing viral transmission. However, no study has evaluated the impact of wearing facemasks during exercise on dyspnea in patients with chronic pulmonary infections from multifaceted aspects, including sensory qualities and emotional responses. The aim of this study was to evaluate facemask-related dyspnea during exercise in this patient population. METHODS: We conducted a randomized crossover study involving adult patients with non-tuberculous mycobacterial pulmonary disease (NTM-PD) or bronchiectasis who participated in exercise sessions, both with (mask-on) and without (mask-off) surgical facemasks. The sensory and emotional dimensions of dyspnea during each exercise session were assessed using the Multidimensional Dyspnea Profile. Statistical analyses were performed to identify factors associated with worsening scores for each dimension. RESULTS: Thirty-four patients (mean age [standard deviation]: 71.6 [8.6] years) were included in the analysis. The median [interquartile range] total scores for the sensory and emotional dimensions of dyspnea were 3.5 [1, 9.5] (mask-off) vs. 10 [5.5, 23.8] (mask-on) (P < 0.001) and 0 [0, 5] (mask-off) vs. 3 [0.8, 10.3] (mask-on) (P = 0.115), respectively. "Air hunger" was the primary sensory descriptor of mask-related dyspnea. Vital capacity (VC) < 80% of the predicted value was a significant risk factor for worsening sensory dimension scores when wearing masks (odds ratio [95% confidence interval]: 5.5 [1.16-26.1], P = 0.038). CONCLUSIONS: The findings of this study indicate that patients with NTM-PD or bronchiectasis, particularly those with VC <80% of the predicted value, are likely to experience the sensory dimension of dyspnea during exercise while wearing surgical facemasks.

Effect of biologic therapy on the humoral immune response to the BNT162b2 vaccine in patients with asthma.

The effect of inhaled corticosteroids (ICS) and biologics on the humoral immune response following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination in patients with asthma is unknown. We prospectively evaluated the humoral immune response 3 weeks (T1) and 6 months (T2) after the second dose of BNT162b2 in 30 SARS-CoV-2-naïve patients with asthma. We measured anti-spike immunoglobulin G (IgG) titers and serum-neutralizing activity against the ancestral SARS-CoV-2 strain. The anti-spike IgG titer and neutralizing activity did not differ significantly between the biologics and non-biologics groups at T1 (P = 0.708 and P = 0.417, respectively) or T2 (P = 0.299 and P = 0.492, respectively). In the multivariate analysis, age and sex were significantly associated with the magnitude of the humoral immune response; however, the use of biologics and ICS dose were not, suggesting that these would not affect BNT162b2 immunogenicity in patients with asthma. Larger studies are needed to validate these findings.

Impact of methotrexate on humoral and cellular immune responses to SARS-CoV-2 mRNA vaccine in patients with rheumatoid arthritis.

The aim of this study was to longitudinally evaluate the undetermined impact of methotrexate (MTX) on the cumulative immunogenicity elicited by three doses of SARS-CoV-2 mRNA vaccination in patients with rheumatoid arthritis (RA). We prospectively evaluated vaccine-induced immune responses following the first dose, 1 and 6 months after the second dose, and 1 month after the third dose of BNT162b2 or mRNA-1273 in 144 SARS-CoV-2 naïve participants (70 patients with RA, 29 disease controls without immunosuppressive conditions, and 45 healthy controls). Humoral immune responses were assessed by quantifying anti-spike IgG antibody titers and the capacity of circulating antibodies to neutralize the ancestral SARS-CoV-2 strain and the Alpha, Delta, and Omicron variants. Vaccine-induced T-cell responses were measured using an interferon-gamma release assay. At 1 and 6 months after the second dose, anti-spike titers were highest in healthy controls, followed by disease controls and patients with RA. Multivariate analyses revealed that MTX treatment was significantly associated with a decrease in anti-spike titers, neutralizing activity, and SARS-CoV-2-specific interferon-gamma levels. Furthermore, MTX dose per body weight was negatively correlated with these two indices of humoral immune response. The third vaccine dose boosted anti-spike titers, especially in patients receiving MTX, while sera from these patients neutralized the Omicron variant far less robustly than those from healthy controls. In conclusion, MTX attenuated immunogenicity following two doses of SARS-CoV-2 mRNA vaccine in patients with RA, particularly resulting in dose-dependent suppression of the humoral immune response. Furthermore, MTX deteriorated the neutralizing activity against the Omicron variant, even after the third immunization.

Factors Associated With the Development of Bacterial Pneumonia Related to Seasonal Influenza Virus Infection: A Study Using a Large-scale Health Insurance Claim Database.

Background: Influenza-related bacterial pneumonia is a leading complication of influenza infection. However, the differences in the incidence rates and risk factors associated with concomitant viral/bacterial pneumonia (CP) and secondary bacterial pneumonia following influenza (SP) remain unclear. This study aimed to clarify the incidence rates of CP and SP following seasonal influenza and identify factors associated with their development. Methods: This retrospective cohort study was conducted using the JMDC Claims Database, a health insurance claims database in Japan. All patients aged <75 years who developed influenza during 2 consecutive epidemic seasons, 2017/2018 and 2018/2019, were analyzed. CP was defined as bacterial pneumonia diagnosed between 3 days before and 6 days after the date of influenza diagnosis, and SP was defined as pneumonia diagnosed 7-30 days after the date of diagnosis. Multivariable logistic regression analyses were performed to identify factors associated with the development of CP and SP. Results: Among the 10 473 014 individuals registered in the database, 1 341 355 patients with influenza were analyzed. The average age at diagnosis (SD) was 26.6 (18.6) years. There were 2901 (0.22%) and 1262 (0.09%) patients who developed CP and SP, respectively. Age 65-74 years, asthma, chronic bronchitis/emphysema, cardiovascular disease, renal disease, malignant tumor, and immunosuppression were significant risk factors for both CP and SP, whereas cerebrovascular disease, neurological disease, liver disease, and diabetes were risk factors specific to CP development. Conclusions: The results determined the incidence rates of CP and SP and identified their risk factors, such as older age and comorbidities.

Protein C activity as a potential prognostic factor for nursing home-acquired pneumonia.

INTRODUCTION: Despite the poor prognosis for nursing home acquired pneumonia (NHAP), a useful prognostic factor is lacking. We evaluated protein C (PC) activity as a predictor of in-hospital death in patients with NHAP and community-acquired pneumonia (CAP). METHODS: This prospective, observational study included all patients hospitalized with pneumonia between July 2007 and December 2012 in a single hospital. We measured PC activity at admission and investigated whether it was different between survivors and non-survivors. We also examined whether PC activity < 55% was a predictor for in-hospital death of pneumonia by logistic regression analysis with CURB-65 items (confusion, blood urea >20 mg/dL, respiratory rate >30/min, and blood pressure <90/60 mmHg, age >65). When it was a useful prognostic factor for pneumonia, we combined PC activity with the existing prognostic scores, the pneumonia severity index (PSI) and CURB-65, and analyzed its additional effect by comparing the areas under the receiver operating characteristic curves (AUCs) of the modified and original scores. RESULTS: Participants comprised 75 NHAP and 315 CAP patients. PC activity was lower among non-survivors than among survivors in NHAP and all-pneumonia (CAP+NHAP). PC activity <55% was a useful prognostic predictor for NHAP (Odds ratio 7.39 (95% CI; 1.59-34.38), and when PSI or CURB-65 was combined with PC activity, the AUC improved (from 0.712 to 0.820 for PSI, and 0.657 to 0.734 for CURB-65). CONCLUSIONS: PC activity was useful for predicting in-hospital death of pneumonia, especially in NHAP, and became more useful when combined with the PSI or CURB-65.

Development and validation of a new scoring system for prognostic prediction of community-acquired pneumonia in older adults.

The discriminative power of CURB-65 for mortality in community-acquired pneumonia (CAP) is suspected to decrease with age. However, a useful prognostic prediction model for older patients with CAP has not been established. This study aimed to develop and validate a new scoring system for predicting mortality in older patients with CAP. We recruited two prospective cohorts including patients aged ≥ 65 years and hospitalized with CAP. In the derivation (n = 872) and validation cohorts (n = 1,158), the average age was 82.0 and 80.6 years and the 30-day mortality rate was 7.6% (n = 66) and 7.4% (n = 86), respectively. A new scoring system was developed based on factors associated with 30-day mortality, identified by multivariate analysis in the derivation cohort. This scoring system named CHUBA comprised five variables: confusion, hypoxemia (SpO2 ≤ 90% or PaO2 ≤ 60 mmHg), blood urea nitrogen ≥ 30 mg/dL, bedridden state, and serum albumin level ≤ 3.0 g/dL. With regard to 30-day mortality, the area under the receiver operating characteristic curve for CURB-65 and CHUBA was 0.672 (95% confidence interval, 0.607-0.732) and 0.809 (95% confidence interval, 0.751-0.856; P < 0.001), respectively. The effectiveness of CHUBA was statistically confirmed in the external validation cohort. In conclusion, a simpler novel scoring system, CHUBA, was established for predicting mortality in older patients with CAP.

Pneumonia Caused by Severe Acute Respiratory Syndrome Coronavirus 2 and Influenza Virus: A Multicenter Comparative Study.

BACKGROUND: Detailed differences in clinical information between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia (CP), which is the main phenotype of SARS-CoV-2 disease, and influenza pneumonia (IP) are still unclear. METHODS: A prospective, multicenter cohort study was conducted by including patients with CP who were hospitalized between January and June 2020 and a retrospective cohort of patients with IP hospitalized from 2009 to 2020. We compared the clinical presentations and studied the prognostic factors of CP and IP. RESULTS: Compared with the IP group (n = 66), in the multivariate analysis, the CP group (n = 362) had a lower percentage of patients with underlying asthma or chronic obstructive pulmonary disease (P < .01), lower neutrophil-to-lymphocyte ratio (P < .01), lower systolic blood pressure (P < .01), higher diastolic blood pressure (P < .01), lower aspartate aminotransferase level (P < .05), higher serum sodium level (P < .05), and more frequent multilobar infiltrates (P < .05). The diagnostic scoring system based on these findings showed excellent differentiation between CP and IP (area under the receiver operating characteristic curve, 0.889). Moreover, the prognostic predictors were different between CP and IP. CONCLUSIONS: Comprehensive differences between CP and IP were revealed, highlighting the need for early differentiation between these 2 pneumonias in clinical settings.

Risk factors associated with methicillin-resistant Staphylococcus aureus isolation from serially collected sputum samples of patients hospitalized with pneumonia.

INTRODUCTION: Risk factors associated with the new detection of methicillin-resistant Staphylococcus aureus (MRSA) during hospitalization remain unclear. This study aimed to identify risk factors associated with MRSA isolation from the sputum of patients admitted with pneumonia, during their hospitalization. METHODS: Patients were prospectively enrolled from 2003 to 2012. Sputum samples were collected for bacterial cultures on days 1, 4, 7, 11, and 14 of hospitalization and thereafter. Cases of MRSA first isolated from sputum obtained before day 4 were defined as "carriage on admission." Cases of MRSA first isolated on day 4 and thereafter, were defined as "new detection after admission." Statistical analysis was used to investigate the risk factors associated with MRSA isolation. RESULTS: MRSA was isolated from 167 of 1,008 patients (carriage: 47; new detection: 120). Multivariate analysis revealed that the risk factors for MRSA carriage were activities of daily living (ADL) disability prior to admission (odds ratio [OR], 2.92; 95% confidence interval [CI], 1.37-6.22) and hospitalization within the previous 90 days (OR, 3.75; 95% CI, 1.90-7.41). ADL disability prior to admission (risk ratio [RR], 1.82; 95% CI, 1.17-2.84) and a high pneumonia severity index score upon admission (RR, 2.20; 95% CI, 1.37-3.65) were risk factors for new detection of MRSA. CONCLUSIONS: Several risk factors were found to be associated with MRSA carriage and/or its new detection, based on the sputum samples from patients admitted with pneumonia. These factors may be indicators for selective surveillance and the early implementation of infection control measures.

Comparison of ceftriaxone plus macrolide and ampicillin/sulbactam plus macrolide in treatment for patients with community-acquired pneumonia without risk factors for aspiration: an open-label, quasi-randomized, controlled trial.

BACKGROUND: Ceftriaxone (CTRX) and ampicillin/sulbactam (ABPC/SBT) are recommended by various guidelines as the first-line antibiotics for community-acquired pneumonia (CAP). However, which of these antibiotics is more effective for treating non-aspiration CAP remains unclear. METHODS: This study was a prospective, single-center, open-label, quasi-randomized controlled trial. Patients with adult CAP without risk for aspiration were allocated to either a CTRX or ABPC/SBT group based on the date of hospital admission. Macrolide was added to patients in each group. The primary outcome was the clinical response in the validated per-protocol (VPP) population at end of treatment (EOT). The secondary outcomes were clinical response during treatment and at end of study (EOS) in the VPP population, and mortality rate at day 30 in the modified intention-to-treat (MITT) population. RESULTS: Of 696 screened patients, 433 patients were excluded and 263 patients were allocated to receive either of the treatments. Males comprised 54% of patients and mean age and PSI were 62.1 ± 19.8 years and 69.3 ± 30.0, respectively, with 124 patients allocated to the CTRX group and 138 patients allocated to the ABPC/SBT group. The clinical effectiveness rate for the VPP population at EOT was 90% in the CTRX and 96% in the ABPC/SBT group (p = 0.072, 95% confidence interval [CI] of risk difference [RD]: - 12.6-0.8%). No significant difference in effectiveness at day 4 was observed between the CTRX and ABPC/SBT groups (p = 0.079, 95%CI of RD: - 12.1-0.4%), but at day 7, ABPC/SBT was significantly more effective than CTRX in the VPP population (p = 0.047, 95%CI of RD: - 13.3--0.4%). No significant difference in late response at EOS was seen between CTRX and ABPC/SBT groups: cure (89 [86%] and 102 [94%]), relapse (5 [5%] and 1 [1%]) and failure (10 [10%] and 5 [5%]; p = 0.053). Deaths within 30 days in MITT population was higher in CTRX group (4 [3%]) than in ABPC/SBT group (0 [0%]) (p = 0.048, 95%CI of RD: 0.1-6.3%). CONCLUSION: No significant difference in effectiveness was found between ABPC/SBT and CTRX at EOT. However, ABPC/SBT might be more effective in the early phase of treatment. TRIAL REGISTRATION: UMIN-CTR, UMIN000037464. Registered 25 July 2019 - Retrospectively registered, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000042262.

Cefepime vs. meropenem for moderate-to-severe pneumonia in patients at risk for aspiration: An open-label, randomized study.

BACKGROUND: Treatment of aspiration pneumonia is an important problem due to aging of populations worldwide. However, the effectiveness of cefepime in aspiration pneumonia has not yet been evaluated. AIM: To compare the clinical efficacy and safety of cefepime and meropenem in patients with moderate-to-severe aspiration pneumonia. METHODS: In this open-label, randomized study, either cefepime 1 g or meropenem 0.5 g was administered intravenously every 8 h to patients with moderate-to-severe community-acquired or nursing-home acquired pneumonia at risk for aspiration for an average of 10.5 days. The primary outcome was the clinical response rate at the end of treatment (EOT) in the validated per-protocol (VPP)-population. Secondary outcomes were clinical response during treatment (days 4 and 7) and at the end of study (EOS) in the VPP-population, and survival at day 30 in the modified intention-to-treat (MITT)-population. RESULTS: There was no difference between the groups in the primary or secondary outcomes or safety. Significant improvement was observed in each group on day 4. CONCLUSION: Cefepime is as effective and safe as meropenem in the treatment of moderate-to-severe aspiration pneumonia. CLINICAL TRIALS IDENTIFIER: UMIN000001349.