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The present investigation work compares cycling ageing behaviour upon constant operation conditions (static tests) with degradation under non-constant schemes (dynamic tests), through a novel methodology for ageing model dynamic validation. A LFP-based Li-ion cell performance loss is analysed using a DOD and C-rate stress factors Ah-throughput-domain characterisation method, and represented using a semi-empirical model. The proposed stepwise validation approach enables assessing the static ageing tests acceleration factor and systematically improving the ageing model. The result is a simple but comprehensive model. The predictions root-mean-square error, under dynamic cycling operation conditions, is just 1.75%. [ABSTRACT FROM AUTHOR]

Background: Recent randomised clinical trials in bronchiectasis have failed to reach their primary end-points, suggesting a need to reassess how we measure treatment response. Exacerbations, quality of life (QoL) and lung function are the most common end-points evaluated in bronchiectasis clinical trials. We aimed to determine the relationship between responses in terms of reduced exacerbations, improved symptoms and lung function in bronchiectasis., Methods: We evaluated treatment response in three randomised clinical trials that evaluated mucoactive therapy (inhaled mannitol), an oral anti-inflammatory/antibiotic (azithromycin) and an inhaled antibiotic (aztreonam). Treatment response was defined by an absence of exacerbations during follow-up, an improvement of QoL above the minimum clinically important difference and an improvement in forced expiratory volume in 1 s (FEV 1 ) of ≥100 mL from baseline., Results: Cumulatively the three trials included 984 patients. Changes in FEV 1 , QoL and exacerbations were heterogeneous in all trials analysed. Improvements in QoL were not correlated to changes in FEV 1 in the azithromycin and aztreonam trials (r= -0.17, p=0.1 and r=0.04, p=0.4, respectively) and weakly correlated in the mannitol trial (r=0.22, p<0.0001). An important placebo effect was observed in all trials, especially regarding improvements in QoL. Clinical meaningful lung function improvements were rare across all trials evaluated, suggesting that FEV 1 is not a responsive measure in bronchiectasis., Conclusions: Improvements in lung function, symptoms and exacerbation frequency are dissociated in bronchiectasis. FEV 1 is poorly responsive and poorly correlated with other key outcome measures. Clinical parameters are poorly predictive of treatment response, suggesting the need to develop biomarkers to identify responders., Competing Interests: Conflict of interest: O. Sibila has nothing to disclose. Conflict of interest: E. Laserna has nothing to disclose. Conflict of interest: A. Shoemark has nothing to disclose. Conflict of interest: L. Perea has nothing to disclose. Conflict of interest: D. Bilton has nothing to disclose. Conflict of interest: M.L. Crichton reports personal fees from AstraZeneca, outside the submitted work. Conflict of interest: A. De Soyza reports grants, travel support to attend international congresses and lecture fees from AstraZeneca, Bayer, Chiesi, Grifols, GlaxoSmithKline, Insmed, Pfizer, Novartis, Medimmune and Zambon, outside the submitted work. Conflict of interest: W.G. Boersma has nothing to disclose. Conflict of interest: J. Altenburg has nothing to disclose. Conflict of interest: J.D. Chalmers reports grants and personal fees from GlaxoSmithKline, Grifols, Boehringer Ingelheim and Insmed, grants from AstraZeneca and Bayer Healthcare, personal fees from Aradigm, Pfizer and Napp, outside the submitted work., (Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.)

Rationale: The principal underlying inhaled antibiotic treatment in bronchiectasis is that airway bacterial load drives inflammation, and therefore antibiotic treatment will reduce symptoms. Objectives: To determine the relationship between bacterial load and clinical outcomes, assess the stability of bacterial load over time, and test the hypothesis that response to inhaled antibiotics would be predicted by baseline bacterial load. Methods: We performed three studies. Studies 1 and 2 were prospective studies including adults with bronchiectasis. Study 3 was a post hoc analysis of a randomized trial of inhaled aztreonam. A priori patients were divided into low (<10 5 cfu/g), moderate (10 5 -10 6 cfu/g), and high bacterial load (≥10 7 cfu/g) using quantitative sputum culture. Measurements and Main Results: Bacterial load was a stable trait associated with worse quality of life and more airway inflammation in studies 1, 2, and 3. In study 3, patients with high bacterial load showed an improvement in the primary endpoint (Quality of Life-Bronchiectasis-Respiratory Symptoms Score at Week 4) in favor of aztreonam (mean difference of 9.7 points; 95% confidence interval, 3.4-16.0; P  = 0.003). The proportion of patients who achieved an increase above the minimum clinically important difference was higher in the aztreonam group at Week 4 (63% vs. 37%; P  = 0.01) and at Week 12 (62% vs. 38%; P  = 0.01) only in high bacterial load patients. Conclusions: Improvement of quality of life with inhaled aztreonam was only evident in patients with high bacterial load. Bacterial load may be a useful biomarker of severity of disease and treatment response.

Background and Objective: Current guidelines recommend empirical treatment against Pseudomonas aeruginosa in community-acquired pneumonia (CAP) patients with specific risk factors. However, evidence to support these recommendations is limited. We evaluate the risk factors and the impact of antimicrobial therapy in patients hospitalized with CAP due to P. aeruginosa., Methods: We performed a retrospective population-based study of >150 hospitals. Patients were included if they had a diagnosis of CAP and P. aeruginosa was identified as the causative pathogen. Univariate and multivariate analyses were performed using the presence of risk factors and 30-day mortality as the dependent measures., Results: Seven hundred eighty-one patients with P. aeruginosa pneumonia were identified in a cohort of 62 689 patients with pneumonia (1.1%). Of these, 402 patients (0.6%) were included in the study and 379 (0.5%) were excluded due to health care-associated pneumonia or immunosuppression. In patients with CAP due to P. aeruginosa, 272 (67.8%) had no documented risk factors. These patients had higher rates of dementia and cerebrovascular disease. Empirical antibiotic therapy against P. aeruginosa within the first 48 h of presentation was independently associated with lower 30-day mortality in patients with CAP due to P. aeruginosa (hazard ratio (HR) 0.42, 95% confidence interval (CI): 0.23-0.76) and in patients without risk factors for P. aeruginosa CAP (HR 0.40, 95% CI: 0.21-0.76)., Conclusions: Risk factor recommended by current guidelines only detect one third of the patients admitted with CAP due to P. aeruginosa. Risk factors did not define the whole benefit observed due to empirical therapy covering P. aeruginosa., (Published 2015. This article is a U.S. Government work and is in the public domain in the USA.)

Background: Several studies have described a clinical benefit of macrolides due to their immunomodulatory properties in various respiratory diseases. We aimed to assess the effect of macrolide therapy on mortality in patients hospitalized for Pseudomonas aeruginosa community-acquired pneumonia (CAP)., Methods: We performed a retrospective population-based study of &gt; 150 hospitals in the US Veterans Health Administration. Patients were included if they had a diagnosis of CAP and P aeruginosa was identified as the causative pathogen. Patients with health-care-associated pneumonia and immunosuppression were excluded. Macrolide therapy was considered when administered within the first 48 h of admission. Univariate and multivariable analyses were performed using 30-day mortality as the dependent measure., Results: We included 402 patients with P aeruginosa CAP, of whom 171 (42.5%) received a macrolide during the first 48 h of admission. These patients were older and white. Macrolide use was not associated with lower 30-day mortality (hazard ratio, 1.14; 95% CI, 0.70-1.83; P = .5). In addition, patients treated with macrolides had no differences in ICU admission, use of mechanical ventilation, use of vasopressors, and length of stay (LOS) compared with patients not treated with macrolides. A subgroup analysis among patients with P aeruginosa CAP in the ICU showed no differences in baseline characteristics and outcomes., Conclusions: Macrolide therapy in the first 48 h of admission is not associated with decreased 30-day mortality, ICU admission, need for mechanical ventilation, and LOS in hospitalized patients with P aeruginosa CAP. Larger cohort studies should address the benefit of macrolides as immunomodulators in patients with P aeruginosa CAP.

There is controversy regarding the impact of chronic obstructive pulmonary disease (COPD) in clinical outcomes in elderly patients with pneumonia. Comorbidities such as cardiovascular disease have been reported to play an important role in patients with acute exacerbations of COPD. However, limited data are available regarding the impact of cardiovascular disease in elderly COPD patients who require hospitalisation for pneumonia. We examined a cohort of subjects with pneumonia and pre-existing COPD. Prior cardiovascular disease was defined as history of myocardial infarction, congestive heart failure, cardiac arrhythmia, unstable angina or stroke. Outcomes examined included 30-day, 90-day, 6-month and 1-year mortality. We included 17,140 elderly COPD patients who were hospitalised for pneumonia. Prior cardiovascular disease was present in 10 240 (59.7%) patients. Prior cardiovascular disease was independently associated with 90-day mortality (21.3% versus 19.4%; hazard ratio (HR) 1.29, 95% CI 1.02-1.17), 6-month mortality (29.0% versus 26.1%; HR 1.28, 95% CI 1.07-1.50) and 12-month mortality (39.2% versus 34.5%; HR 1.33, 95% CI 1.15-1.54) when compared to no prior cardiovascular disease. The temporal differential effect between groups increases from 1.0% at 30 days to 4.7% at 1 year. Prior cardiovascular disease is associated with increased long-term mortality in elderly COPD patients with pneumonia. Differences in mortality rates increased over time.

Background: Limited information is available regarding the impact of prior use of inhaled corticosteroids (ICS) in patients subsequently developing community-acquired pneumonia (CAP). We assessed the effects of prior ICS use on severity of illness and microbiology in CAP hospitalized patients., Methods: A retrospective cohort study of subjects with CAP (by the International Classification of Diseases, 9th Revision, Clinical Modification) was conducted over a 4-year period at 2 tertiary teaching hospitals. Subjects were considered to be ICS users if they received ICS prior to admission. Primary outcomes were severity of illness and microbiology at admission., Results: Data were abstracted on 664 subjects: 89 prior ICS users (13.4%) and 575 non-users (86.6%). Prior ICS users had higher severity of illness at admission: mean ± SD Pneumonia Severity Index 100.8 ± 31.4 vs 68.8 ± 33.4, P = .001, and CURB-65 (confusion, urea nitrogen, respiratory rate, blood pressure, ≥ 65 years of age) score 1.56 ± 1.02 vs 1.19 ± 1.02, P = .002. Prior ICS use was independently associated with antimicrobial-resistant pathogens: 11.2% vs 5.9%, odds ratio 2.6, 95% CI 1.1-6.1, P = .04., Conclusions: Prior ICS use was associated with higher severity of illness at admission and higher incidence of antimicrobial-resistant pathogens in CAP hospitalized patients.

Purpose: To improve 2007 Infectious Disease Society of America/American Thoracic Society (IDSA/ATS) severity criteria to predict intensive care unit (ICU) admission in patients hospitalized with pneumonia., Methods: A composite score that included the 2007 IDSA/ATS criteria for severe pneumonia and additional significant variables identified by recent publications was tested in patients hospitalized with community-acquired pneumonia., Results: Among 787 patients hospitalized with community-acquired pneumonia, 156 (19.8%) required admission to the ICU. We identified one major criterion (arterial pH <7.30), and 4 minor criteria (tachycardia >125 bpm, arterial pH 7.30-7.34, sodium <130 mEq/L and glucose >250 mg/dL) to be associated with ICU admission. Adding arterial pH <7.30 to the 2 2007 IDSA/ATS major criteria increased sensitivity from 61.5% to 71.8% and area under the curve (AUC) from 0.80 to 0.86. Adding in sequence the four minor criteria to the 2007 IDSA/ATS minor criteria, increased sensitivity from 41.7% to 53.8%, and AUC from 0.65 to 0.69. In the new composite score, combining 1 of 3 major criteria with 3 of 12 minor criteria showed a sensitivity of 92.9% and an AUC of 0.88., Conclusion: The addition of arterial pH <7.30 to the 2007 IDSA/ATS major criteria improves sensitivity and AUC to identify patients who will require ICU care., (Published by Elsevier Inc.)

Background and Objective: Limited information is available regarding the impact of prior outpatient use of systemic corticosteroids (SCS) in patients subsequently developing community-acquired pneumonia (CAP). We investigate the effects of prior SCS on severity of illness, microbiology and clinical outcomes for patients hospitalized with CAP., Methods: A retrospective cohort study of subjects with CAP (according to International Classification of Diseases, 9th edition codes) was conducted over a 3-year period at two tertiary teaching hospitals. Subjects were considered to be SCS users if they received oral corticosteroids prior to admission. Primary outcomes were severity of illness, microbiology and 30-day mortality., Results: Data were abstracted on 698 patients [prior SCS users, 75 (10.7%) versus prior non-SCS users 623 (89.3%)]. Prior SCS users were more likely to have chronic obstructive pulmonary disease. No differences were found in severity of disease at admission, microbiological etiology including opportunistic and drug-resistant pathogens and clinical outcomes, including 30-day mortality, intensive care unit admission, length of hospital stay, need for mechanical ventilation and need for vasopressors., Conclusion: Prior SCS use is not associated with increased 30-day mortality for patients hospitalized with CAP. In addition, no differences were found in either the severity of the disease at the time of presentation or in the presence of the resistant or opportunistic pathogens among groups.

Objective: The purpose of our study was to examine in patients hospitalized with community acquired pneumonia (CAP) the association between abnormal Pa CO 2 and ICU admission and 30-day mortality., Methods: A retrospective cohort study was conducted at two tertiary teaching hospitals. Eligible subjects were admitted with a diagnosis of CAP. Arterial blood gas analyses were obtained with measurement of PaCO2 on admission. Multivariate analyses were performed using 30-day mortality and ICU admission as the dependent measures., Results: Data were abstracted on 453 subjects with a documented arterial blood gas analysis. One hundred eighty-nine patients (41%) had normal PaCO2 (35-45 mm Hg), 194 patients (42%) had aPa CO 2 , 35 mm Hg (hypocapnic), and 70 patients (15%) had a Pa CO 2 . 45 mm Hg (hypercapnic).In the multivariate analysis, after adjusting for severity of illness, hypocapnic patients had greater 30-day mortality (OR= 2.84; 95% CI, 1.28-6.30) and a higher need for ICU admission (OR= 2.88;95% CI, 1.68-4.95) compared with patients with normal PaCO2. In addition, hypercapnic patients had a greater 30-day mortality (OR= 3.38; 95% CI, 1.38-8.30) and a higher need for ICU admission(OR =5.35; 95% CI, 2.80-10.23). When patients with COPD were excluded from the analysis,the differences persisted between groups., Conclusion: In hospitalized patients with CAP, both hypocapnia and hypercapnia were associated with an increased need for ICU admission and higher 30-day mortality. These findings persisted after excluding patients with CAP and with COPD. Therefore, PaCO2 should be considered for inclusion in future severity stratification criteria to appropriate identified patients who will require a higher level of care and are at risk for increased mortality.

Introduction: Our aim was to evaluate the minor criteria recommended by the 2007 Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) as predictors of 30-day mortality, the need for invasive mechanical ventilation, and/or the need for vasopressor support as markers of severity in patients hospitalized with community-acquired pneumonia (CAP)., Methods: Patients admitted to 2 academic teaching hospitals over a 4-year period (January 1, 1999 to December 1, 2002) were identified as having CAP. We used modified minor criteria established by the 2007 IDSA/ATS guidelines. The primary outcome measure was 30-day mortality, and the secondary outcome measures were need for invasive mechanical ventilation and/or need for vasopressor support., Results: About half of the patients in the cohort (n = 352/787 [46%]) had ≥ 1 minor criterion, but only 128 (16.3%) had ≥ 3 minor criteria present at hospital admission. In the multivariable analysis, hypoxemia, multilobar infiltrates, and leukopenia were associated with 30-day mortality (P < 0.05). In addition, hypoxemia and confusion/disorientation were associated with the need for invasive mechanical ventilation and/or vasopressor support (P < 0.05). The presence of ≥ 3 minor criteria was associated with 30-day mortality (odds ratio, 4.82), and the need for invasive mechanical ventilation and/or vasopressor support (odds ratio, 2.59)., Conclusion: Our results show that hypoxemia, multilobar infiltrates, and leukopenia were the most predictive minor criteria for 30-day mortality. In contrast, hypoxemia and confusion/disorientation were the 2 individual minor severe criteria that were more likely to require invasive mechanical ventilation and/or vasopressor support. At least 3 2007 IDSA/ATS minor severe criteria were associated with 30-day mortality and need for invasive mechanical ventilation and/or vasopressor support.

Objective: To identify patients with a low short-term risk of complications following acute pulmonary thromboembolism., Patients and Methods: A prospective multicenter study was conducted in 8 Spanish hospitals; 681 consecutive outpatients diagnosed with pulmonary thromboembolism were enrolled. Clinically significant variables were weighted using coefficients derived from a logistic regression model in order to optimize the diagnostic performance of a clinical prediction rule to predict the following complications within 10 days of acute pulmonary thromboembolism: death, recurrent thromboembolism, and major or minor bleeding., Results: Forty-three patients (6.3%) had 51 complications. These included 33 deaths, 12 major bleeding episodes, and 6 minor bleeding episodes. The clinical variables used in the prediction rule were assigned the following scores: recent major bleeding episode and cancer with metastasis, 4 points each; creatinine levels of over 2 mg/dL, 3 points; cancer without metastasis and immobility due to a recent medical condition, 2 points each; and absence of surgery in the past 2 months and an age of over 60 years, 1 point each. A risk score of 2 or less, obtained by 47.8% of patients, indicated a low short-term risk of developing complications following pulmonary thromboembolism. The area under the receiver operating characteristic curve for the prediction rule was 0.75 (95% confidence interval [CI], 0.67-0.83). For this cutoff point, sensitivity was 82.9% (95% CI, 68.7-91.5) and the likelihood ratios for a positive and negative test result were 1.63 (95% CI, 1.39-1.92), and 0.35 (95% CI, 0.18-0.69), respectively., Conclusions: Our clinical prediction rule could be useful for identifying patients with a low risk of complications in the 10 days following acute pulmonary thromboembolism. Those patients would be eligible for consideration for outpatient treatment.

Objective: To assess the performance of two prognostic models in predicting short-term mortality in patients with pulmonary embolism (PE)., Subjects and Methods: We compared the test characteristics of two prognostic models for predicting 30-day outcomes (mortality, thromboembolic recurrences, and major bleeding) in a cohort of 599 patients with objectively confirmed PE. Patients were stratified into the PE severity index (PESI) risk classes I-V and the Geneva low-risk and high-risk strata. We compared the discriminatory power of both prognostic models., Results: The PESI classified fewer patients as low risk (strata I and II) [36%; 216 of 599 patients; 95% confidence interval (CI), 32 to 40%] compared to the Geneva prediction rule (84%; 502 of 599 patients; 95% CI, 81 to 87%) [p < 0.0001]. Using either prediction rule, the low-risk groups showed statistically relevant 30-day mortality difference (PESI, 0.9%; 95% CI, 0.3 to 2.2; vs Geneva, 5.6%; 95% CI, 3.6 to 7.6) [p < 0.0001], although nonfatal recurrent venous thromboembolism or major bleeding rates were statistically similar (PESI, 2.8%; 95% CI, 0.6 to 5.0%; vs Geneva, 4.2%; 95% CI, 2.4 to 5.9%). The area under the receiver operating characteristic curve was higher for the PESI (0.76; 95% CI, 0.69 to 0.83) than for the Geneva score (0.61; 95% CI, 0.51 to 0.71) [p = 0.002]., Conclusions: The PESI quantified the prognosis of patients with PE better than the Geneva score. This study demonstrated that PESI can select patients with very low adverse event rates during the initial days of acute PE therapy and assist in selecting patients for treatment in the outpatient setting.

Background and Objective: Mortality, recurrences and hemorrhages are the most serious early complications of pulmonary embolism (PE). We intended to ascertain the frequency and mechanisms of complications within the first 10 days after PE was diagnosed., Patients and Method: We included patients suspected of suffering PE between December 2003 and August 2004 from 8 hospitals. We performed a multicenter observational prospective study of 8 Spanish hospitals with consecutive outpatients diagnosed with PE. Database of clinical variables: computerized Registry of Patients with Venous Thromboembolism (RIETE). Statistic analysis included chi2 and Student's t test to compare the 2 groups of patients (with and without complications)., Results: Six hundred eighty one patients were included, 336 men and 345 women (mean age 66 and 70, respectively). During the first 10 days, 33 (4.8%) of them died, and 22 (3.2%) had an hemorrhage yet no recurrences appeared. Previous immobilization and the presence of respiratory failure, cancer or renal failure were significantly associated with early complications while previous surgery and thoracic pain were not associated with those., Conclusions: Early complications and some of the associated factors were in agreement with published data. Other situations such as previous surgery or thoracic pain appeared to be protective factors.

Background and Objective: In patients with acute exacerbations of chronic obstructive pulmonary disease (COPD), noninvasive ventilatory support (NPPV) with bilevel positive airway pressure (BiPAP) may improve clinical and physiological parameters. The present study used a randomized, prospective design to evaluate the possible benefits of NPPV plus standard therapy versus standard therapy alone in patients admitted with acute hypercapnic respiratory failure in a respiratory unit of a tertiary hospital., Patients and Method: Forty-one patients were included in the study. Of them, 20 were randomly allocated to receive NPPV with a standard mask connected to a BiPAP ventilatory assist device (Respironics Inc, Murrysville, PA) and 21 to standard therapy. Both groups had similar characteristics upon their admission in the hospital., Results: The use of noninvasive ventilation significantly reduced the respiratory rates and improved the conscious level within the first 2 h (p < 0.001). There were significant differences in PaCO2 and pH (p < 0.05) at 6 h of treatment. The need for intubation was 5% in the NPPV group vs 14% in the control group. The length of hospital stay was significantly shorter in the NPPV group (7 vs 10 days; p < 0.01). Nasal NPPV was well tolerated and complications were uncommon and mild., Conclusions: Early use of noninvasive ventilation in patients with acute exacerbation of chronic obstructive pulmonary disease leads to a more rapid improvement of physiological variables. Moreover, it is possible to apply this treatment in a general respiratory ward.

Non-invasive intermittent positive pressure ventilation (NIPPV) at home is the treatment of choice for patients with chronic respiratory insufficiency secondary to severe kyphoscoliosis. Our aim was to compare clinical course, blood gases and lung function after one month of domiciliary NIPPV with two types of ventilator and to assess sleep pattern changes in patients enrolled in a prospective, randomized crossover study. Ten patients with chronic respiratory insufficiency due to kyphoscoliosis were enrolled and randomly assigned to the first device. After one month of use, the patients underwent clinical and functional examinations and polysomnographic studies while using the ventilator. The same protocol was applied with the second device after a ten-day washout period. Baseline polysomnographs showed fragmented sleep with low percentages of deep non-REM sleep and of REM sleep, as well as respiratory patterns characterized by very high frequencies coinciding with significant desaturations. In all cases symptoms and arterial blood gas improvements were significant, with no differences between the two treatment periods. The percentages of time spent with SaO2 below 90% of reference in sleep studies were significantly lower than baseline with both ventilators. All but one patient had better tolerance of the bilevel positive airway pressure (BIPAP) support mode than of the volumetric ventilator. Our study shows that NIPPV is equally effective for patients with kyphoscoliosis whether administered with a volumetric ventilator or a BIPAP device. Subjective response and tolerance seem to be slightly better with BIPAP.