Reassessing Halm's clinical stability criteria in community-acquired pneumonia management.

INTRODUCTION: Halm's clinical stability criteria have long guided antibiotic treatment and hospital discharge decisions for patients hospitalised with community-acquired pneumonia (CAP). Originally introduced in 1998, these criteria were established based on a relatively small and select patient population. Consequently, our study aims to reassess their applicability in management of CAP in a contemporary real-world setting. METHODS: This cohort study included 2918 immunocompetent patients hospitalised with CAP from three hospitals in Denmark between 2017-2020. The primary outcome was time to achieve clinical stability as defined by Halm's criteria. Additionally, we examined recurrence of clinical instability and severe complications. Cumulative incidence function or Kaplan-Meier survival curves were used to analyse these outcomes, considering competing risks. FINDINGS: The study population primarily comprised elderly individuals (median age: 75 years) with significant comorbidities. The median time to clinical stability according to Halm's criteria was 4 days, with one-fifth experiencing recurrence of instability after early clinical response (stability within 3 days). Severe complications within 30 days mainly comprised mortality, with rates of 5.1% (64/1257) overall in those with early clinical response, 1.7% (18/1045) in the subgroup without do-not-resuscitate orders, and 17.3% (276/1595) among the rest. INTERPRETATION: Halm's clinical stability criteria effectively classify CAP patients with different disease courses, yet achieving stability required more time in this aging population with substantial comorbidities and more severe disease. Early clinical response indicates reduced risk of complications, especially in those without do-not-resuscitate orders.

European Respiratory Society guidelines for the Diagnosis and Management of Pulmonary Alveolar Proteinosis.

BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a rare syndrome caused by several distinct diseases leading to progressive dyspnoea, hypoxemia, risk of respiratory failure and early death due to accumulation of proteinaceous material in the lungs. Diagnostic strategies may include computed tomography (CT) of the lungs, bronchoalveolar lavage, evaluation of antibodies against granulocyte macrophage colony stimulating factor (GM-CSF), genetic testing, and, eventually, lung biopsy. The management options are focused at removing the proteinaceous material by whole lung lavage (WLL), augmentation therapy with GM-CSF, rituximab, plasmapheresis, and lung transplantation. The presented diagnostic and management guideline aim to provide guidance to physicians managing patients with PAP. METHODS: A European Respiratory Society Task Force committee composed of clinicians, methodologists, and patients with experience in PAP developed recommendations in accordance with the ERS Handbook for Clinical Practice Guidelines and the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) approach. This included a systematic review of the literature and application of the GRADE approach to assess the certainty of the evidence and strength of recommendations. The committee formulated five PICO (Patients, Intervention, Comparison, Outcomes) questions, and two narrative questions to develop specific evidence-based recommendations. RESULTS: The Task Force committee developed recommendations for five PICOs. These included management of PAP with WLL, GM-CSF augmentation therapy, rituximab, plasmapheresis, and lung transplantation. Also, the committee made recommendations regarding the use of GM-CSF antibody testing, diagnostic bronchoalveolar lavage (BAL) and biopsy based on narrative questions.In addition to the recommendations, the committee provided information on the hierarchy of diagnostic interventions and therapy. CONCLUSIONS: The diagnosis of PAP is based on CT and BAL cytology or lung histology, whereas diagnosis of specific PAP-causing diseases requires GM-CSF antibody testing or genetic analysis. There are several therapies including WLL and augmentation therapy with GM-CSF available to treat PAP, but supporting evidence is still limited.

Unravelling the complexity of ventilator-associated pneumonia: a systematic methodological literature review of diagnostic criteria and definitions used in clinical research.

BACKGROUND: Ventilator-associated pneumonia (VAP) is a prevalent and grave hospital-acquired infection that affects mechanically ventilated patients. Diverse diagnostic criteria can significantly affect VAP research by complicating the identification and management of the condition, which may also impact clinical management. OBJECTIVES: We conducted this review to assess the diagnostic criteria and the definitions of the term "ventilator-associated" used in randomised controlled trials (RCTs) of VAP management. SEARCH METHODS: Based on the protocol (PROSPERO 2019 CRD42019147411), we conducted a systematic search on MEDLINE/PubMed and Cochrane CENTRAL for RCTs, published or registered between 2010 and 2024. SELECTION CRITERIA: We included completed and ongoing RCTs that assessed pharmacological or non-pharmacological interventions in adults with VAP. DATA COLLECTION AND SYNTHESIS: Data were collected using a tested extraction sheet, as endorsed by the Cochrane Collaboration. After cross-checking, data were summarised in a narrative and tabular form. RESULTS: In total, 7,173 records were identified through the literature search. Following the exclusion of records that did not meet the eligibility criteria, 119 studies were included. Diagnostic criteria were provided in 51.2% of studies, and the term "ventilator-associated" was defined in 52.1% of studies. The most frequently included diagnostic criteria were pulmonary infiltrates (96.7%), fever (86.9%), hypothermia (49.1%), sputum (70.5%), and hypoxia (32.8%). The different criteria were used in 38 combinations across studies. The term "ventilator-associated" was defined in nine different ways. CONCLUSIONS: When provided, diagnostic criteria and definitions of VAP in RCTs display notable variability. Continuous efforts to harmonise VAP diagnostic criteria in future clinical trials are crucial to improve quality of care, enable accurate epidemiological assessments, and guide effective antimicrobial stewardship.

European Respiratory Society guidelines on transbronchial lung cryobiopsy in the diagnosis of interstitial lung diseases.

BACKGROUND: In patients with interstitial lung diseases (ILD), histopathological input is often required to obtain a diagnosis. Surgical lung biopsy (SLB) is considered the reference standard, but many patients are clinically unfit to undergo this invasive procedure, and adverse events, length of hospitalisation and costs are considerable. This European Respiratory Society (ERS) guideline provides evidence-based clinical practice recommendations for the role of transbronchial lung cryobiopsy (TBLC) in obtaining tissue-based diagnosis in patients with undiagnosed ILD. METHODS: The ERS Task Force consisted of clinical experts in the field of ILD and/or TBLC and methodological experts. Four PICO (Patient, Intervention, Comparator, Outcomes) questions and two narrative questions were formulated. Systematic literature searches were performed in MEDLINE and Embase (up to June 2021). GRADE (Grading, Recommendation, Assessment, Development and Evaluation) methodology was applied. RESULTS: In patients with undiagnosed ILD and an indication to obtain histopathological data: 1) TBLC is suggested as a replacement test in patients considered eligible to undergo SLB, 2) TBLC is suggested in patients not considered eligible to undergo SLB, 3) SLB is suggested as an add-on test in patients with a non-informative TBLC, 4) no recommendation is made for or against a second TBLC in patients with a non-informative TBLC and 5) TBLC operators should undergo training, but no recommendation is made for the type of training required. CONCLUSIONS: TBLC provides important diagnostic information in patients with undiagnosed ILD. Diagnostic yield is lower compared to SLB, at reduced serious adverse events and length of hospitalisation. Certainty of the evidence is mostly "very low".

Clinical characteristics of eosinophilic asthma exacerbations.

BACKGROUND AND OBJECTIVE: Airway eosinophilia is associated with an increased risk of asthma exacerbations; however, the impact on the severity of exacerbations is largely unknown. We describe the sputum inflammatory phenotype during asthma exacerbation and correlate it with severity and treatment response. METHODS: Patients presenting to hospital with an asthma exacerbation were recruited during a 12-month period and followed up after 4 weeks. Induced sputum was collected at both visits. Patients underwent spirometry, arterial blood gas analysis, fractional exhaled nitric oxide analysis, white blood cell counts and a screening for common respiratory viruses and bacteria. An eosinophilic exacerbation (EE) was defined as having sputum eosinophils ≥ 3% and a non-eosinophilic exacerbation as < 3% (NEE). RESULTS: A total of 47 patients were enrolled; 37 (79%) had successful sputum induction at baseline, of whom 43% had sputum eosinophils ≥3% (EE). Patients with EE had a significantly lower forced expiratory volume in 1 s (FEV1 ) % predicted (70.8%, P = 0.03) than patients with NEE (83.6%). Furthermore, EE patients were more likely to require supplemental oxygen during admission (63% vs 14%, P = 0.002). The prevalence of respiratory viruses was the same in EE and NEE patients (44% vs 52%, P = 0.60), as was bacterial infection (6% vs 14%, P = 0.44). Fractional expiratory nitric oxide (FeNO) correlated with sputum %-eosinophils (ρ = 0.57, P < 0.001), and predicted airway eosinophilia with a sensitivity of 86% and a specificity of 70%. CONCLUSION: Our findings suggest that eosinophilic asthma exacerbations may be clinically more severe than NEEs, supporting the identification of these higher risk patients for specific interventions.

Endoscopic Ultrasound-Guided Liver Biopsy in the Hands of a Chest Physician.

Liver biopsy using transesophageal bronchoscopic ultrasound-guided fine needle aspiration (EUS-B-FNA) has never been described before and biopsies of infradiaphragmatic lesions using this technique are not considered to be standard. A patient suspected for primary lung cancer with multiple lesions in the liver was referred to our department. We conducted bronchoscopy and endobronchial ultrasound-guided (EBUS) biopsy from several enlarged mediastinal lymph nodes. Thereafter, we conducted EUS-B-FNA from a lesion in the left liver lobe. Pathology showed that the liver lesion represented a metastasis from a pulmonary adenocarcinoma. Bronchoscopy and EBUS samples were not able to establish diagnosis. We hereby demonstrated that a diagnostic EUS-B-FNA from a liver metastasis in a patient with lung cancer is possible. This underlines that chest physicians should not forget the esophagus when staging lung cancer.

Critical appraisal of clinical practice guidelines.

Ten questions to assess to what degree a clinical practice guideline is likely to be trustworthy: 1) Do the authors have conflicts of interests? 2) Is the clinical question relevant? 3) Have relevant stakeholders been involved? 4) Have methods for study selection been described? 5) Is there a link between evidence and recommendations (transparent methods)? 6) Has the certainty of evidence been assessed? 7) Have the methods for reaching recommendations been described? 8) Are the recommendations unambiguous? 9) Are the recommendations relevant in your situation? 10) Is there an implementation strategy?

Short-course antibiotic therapy for hospitalized patients with early clinical response in community-acquired pneumonia: a multicentre cohort study.

OBJECTIVES: To explore whether short-course antibiotic therapy is efficient and safe in routine clinical settings among patients hospitalized with community-acquired pneumonia (CAP) who achieve an early clinical response. METHODS: During 2017-2019, we conducted a cohort study of patients admitted with CAP to four hospitals in Denmark. Data were prospectively gathered from medical records and enriched with data from nationwide registries. In the present study, we included patients with early clinical response and divided them into treatment groups based on antibiotic duration, as decided by the attending physician: short-course (4-7 days) or prolonged-course (8-14 days). The primary outcome was post-treatment mortality within 30 days. Secondary outcomes included readmissions or new antibiotics. Logistic regression models were used to estimate ORs with 95% CIs, and inverse probability weighting was applied to adjust for confounding. RESULTS: The study cohort included 1151 patients with a median age of 74 years, predominantly presenting with mild-moderate disease. The 30-day post-treatment mortality was 3.36% (11/327) in the short-course group and 3.40% (28/824) in the prolonged-course group (adjusted OR 1.05, 95% CI 0.38-1.88). Readmission occurred in 15.6% (42/269) vs. 14.0% (102/727) (adjusted OR 1.07, 95% CI 0.75-1.69) and new prescription of antibiotics in 11.9% (32/269) vs. 12.1% (88/727) (adjusted OR 0.99, 95% CI 0.61-1.49). DISCUSSION: In patients hospitalized with CAP and early clinical response, similar outcomes were observed between short-course and prolonged-course therapies. These results support the use of short-course therapy in routine clinical settings.

Clinical trials of pneumonia management assess heterogeneous outcomes and measurement instruments.

OBJECTIVES: To inform clinical practice guidelines, randomized controlled trials (RCTs) of the management of pneumonia need to address the outcomes that are most important to patients and health professionals using consistent instruments, to enable results to be compared, contrasted, and combined as appropriate. This systematic review describes the outcomes reported in clinical trials of pneumonia management and the instruments used to measure these outcomes. STUDY DESIGN AND SETTING: Based on a prospective protocol, we searched MEDLINE/PubMed, Cochrane CENTRAL and clinical trial registries for ongoing or completed clinical trials evaluating pneumonia management in adults in any clinical setting. We grouped reported outcomes thematically and classified them following the COMET Initiative's taxonomy. We describe instruments used for assessing each outcome. RESULTS: We found 280 eligible RCTs of which 115 (41.1%) enrolled critically ill patients and 165 (58.9%) predominantly noncritically ill patients. We identified 43 distinct outcomes and 108 measurement instruments, excluding nonvalidated scores and questionnaires. Almost all trials reported clinical/physiological outcomes (97.5%). Safety (63.2%), mortality (56.4%), resource use (48.6%) and life impact (11.8%) outcomes were less frequently addressed. The most frequently reported outcomes were treatment success (60.7%), mortality (56.4%) and adverse events (41.1%). There was significant variation in the selection of measurement instruments, with approximately two-thirds used in less than 10 of the 280 RCTs. None of the patient-reported outcomes were used in 10 or more RCTs. CONCLUSION: This review reveals significant variation in outcomes and measurement instruments reported in clinical trials of pneumonia management. Outcomes that are important to patients and health professionals are often omitted. Our findings support the need for a rigorous core outcome set, such as that being developed by the European Respiratory Society.

Novel nested direct PCR technique for malaria diagnosis using filter paper samples.

The use of direct nested PCR enables the detection of Plasmodium spp. from blood samples collected on filter papers without requiring the time-consuming procedures associated with DNA extraction. Direct PCR provides a rapid, highly sensitive, and cost-effective alternative to diagnosing malaria using filter paper samples and standard nested PCR.

Time to antibiotic administration and patient outcomes in community-acquired pneumonia: results from a prospective cohort study.

OBJECTIVES: Community-acquired pneumonia (CAP) is a frequently occurring disease linked to high mortality and morbidity. Previous studies indicated that the administration of antibiotics within 4 hrs of admission can improve key patient outcomes associated with CAP, such as mortality and time to clinical stability. However, the results have been heterogeneous and may not be applicable to all healthcare settings. Therefore, we designed a cohort study to estimate the impact of timely antibiotic administration on outcomes in patients admitted with CAP. METHODS: The impact of antibiotic administration within 4 hrs of admission and other covariates were estimated for 30-day mortality, stability within 72 hrs, 30-day readmission and time to discharge, using multivariable regression models. Sensitivity analyses were performed on a subset of patients with the most severe CAP and a propensity score matched cohort. RESULTS: In total, 2264 patients were included. Of these, 273 (12.1%) died within 30 days of admission, 1277 (56.4%) were alive and stable within 72 hrs and 334 (14.8%) were discharged alive and readmitted within 30 days. Median length of hospital stay was 5 days (interquartile range 3-8). In all models, the administration of antibiotics within 4 hrs of admission had no significant effect on the outcomes. The adjusted odds ratios (OR) derived from the multivariable models for 30-day mortality, stability within 72 hrs and 30-day readmission were 1.01 (95% confidence interval (CI) 0.76; 1.33), 0.88 (95% CI 0.74; 1.05) and 1.05 (95% CI 0.82; 1.34). The adjusted hazard ratio (HR) for time to discharge was 1.00 (95% CI 0.91; 1.10). DISCUSSION: A strict 4-hr threshold for antibiotic administration in all patients admitted with CAP is not reasonable. Instead, our results suggested that patients should be triaged and prioritized according to age, comorbidities, clinical condition and pneumonia severity.

The increasing importance of Haemophilus influenzae in community-acquired pneumonia: results from a Danish cohort study.

BACKGROUND: Numerous studies have shown that the aetiology of community-acquired pneumonia (CAP) varies considerably among different healthcare settings. Because empiric therapies for CAP should cover the major pathogens, reports examining CAP aetiology are considered crucial, particularly in Nordic countries that still rely on penicillin G or V treatments for most patients with CAP. The primary objective of our study was to report CAP aetiology. Secondary objectives included the estimation of positivity rates for different tests and the odds of a positive test for various subgroups. METHODS: In this cohort study, microbiological data were analysed for an overall cohort (variable degree of microbiological testing) and for a subgroup that was tested for both, bacteria, viruses and fungi, using routine methods (defined as extensive testing). RESULTS: The overall cohort comprised 2,264 patients, including 315 who were extensively tested. Bacterial and viral monoinfections were the most commonly identified infections. The dominant pathogen identified among extensively tested patients was Haemophilus influenzae (23.7%), followed by Streptococcus pneumoniae (20.6%). The tests with the highest positivity rates were sputum cultures (34.7%) and viral polymerase chain reaction (PCR, 24.4%). The odds of achieving a microbiological diagnosis increased significantly when extensive testing was performed compared with selective testing (OR 2.86, 95% CI 2.24-3.64). CONCLUSION: Our study indicated that H. influenzae is the dominant responsible pathogen for bacterial CAP in Denmark. Thus, we believe that the current treatment recommendations that encourage the use of penicillin G or V for the majority of patients with CAP need to be revised.

The impact of a stewardship program on antibiotic administration in community-acquired pneumonia: Results from an observational before-after study.

BACKGROUND: A majority of patients with community-acquired pneumonia (CAP) receive antibiotics. According to the evidence, 5-7 days of treatment should be sufficient for most patients. Many, however, are treated longer than recommended. We have previously conducted a quality improvement study to ensure guideline-conform treatment for CAP. However, the impact of the interventions on antibiotic use has not been investigated. OBJECTIVE: To estimate the impact of an eight-month stewardship program on antibiotic use. METHODS: We conducted a before-after study comparing a four-month baseline period with data from a corresponding follow-up period. We performed univariable and multivariable logistic regression to compare odds for ≤7 days of total antibiotic treatment, ≤3 days of intravenous treatment and the proportion of correct empiric antibiotics. As sensitivity analysis, we repeated the univariable logistic regression on a propensity score-matched cohort by using the same variables we used for adjustments in the multivariable analysis. We also performed subgroup analyses for patients stable ≤72 h of admission. RESULTS: In total, 771 patients were included. Compared to preintervention, the unadjusted odds ratio (OR) for ≤7 days of total antibiotic treatment were 1.84 (95% CI 1.34-2.54) for the whole population and 2.08 (1.41-3.10) for the stable patients. The OR for ≤3 days of intravenous antibiotics were 1.16 (0.87-1.54) and 1.38 (0.87-2.22), respectively. The OR for correct empiric antibiotics were 1.96 (1.45-2.68) and 1.82 (1.23-2.69). Comparable results regarding all outcomes were derived from the other analyses. CONCLUSION: The program resulted in a significantly lower overall antibiotic exposure and a higher proportion of patients treated with the recommended antibiotics without a the reduction of exposure to intravenous antibiotics significantly.

Outcomes Evaluated in Controlled Clinical Trials on the Management of COVID-19: A Methodological Systematic Review.

It is crucial that randomized controlled trials (RCTs) on the management of coronavirus disease 2019 (COVID-19) evaluate the outcomes that are critical to patients and clinicians, to facilitate relevance, interpretability, and comparability. This methodological systematic review describes the outcomes evaluated in 415 RCTs on the management of COVID-19, that were registered with ClinicalTrials.gov, by 5 May 2020, and the instruments used to measure these outcomes. Significant heterogeneity was observed in the selection of outcomes and instruments. Mortality, adverse events and treatment success or failure are only evaluated in 64.4%, 48.4% and 43% of the included studies, respectively, while other outcomes are selected less often. Studies focusing on more severe presentations (hospitalized patients or requiring intensive care) most frequently evaluate mortality (72.5%) and adverse events (55.6%), while hospital admission (50.8%) and viral detection/load (55.6%) are most frequently assessed in the community setting. Outcome measurement instruments are poorly reported and heterogeneous. Follow-up does not exceed one month in 64.3% of these earlier trials, and long-term COVID-19 burden is rarely assessed. The methodological issues identified could delay the introduction of potentially life-saving treatments in clinical practice. Our findings demonstrate the need for greater consistency, to enable decision makers to compare and contrast studies.

Improved treatment of community-acquired pneumonia through tailored interventions: Results from a controlled, multicentre quality improvement project.

BACKGROUND: Community-acquired pneumonia (CAP) is one of the leading causes of healthcare utilisation and death worldwide. Treatment according to evidence-based clinical guidelines can reduce mortality, antibiotic exposure and length of hospital stay related to CAP. LOCAL PROBLEM: Several studies, including a pilot study from one of our sites, indicate that physicians show a low grade of guideline adherence when managing patients with CAP. METHODS: To improve the guideline-based treatment of patients with CAP admitted to hospital, we designed a quality improvement study. Four process indicators were combined in a CAP care bundle: chest X-ray, CURB-65 severity score, lower respiratory tract samples and antibiotics within 8 hours from admission. After a 4-month baseline period, we applied multiple interventions at three hospitals during 8 months. Progression in our process indicators was measured continuously and compared with a control site without interventions. After the 8-month intervention period, we continued with a 4-month follow-up period to assess the sustainability of the improvements. RESULTS: The care bundle utilisation rate within 8 hours increased from 11% at baseline to 41% in the follow-up period at the intervention sites, whereas it remained below 3% at the control site. The most considerable improvements have been observed regarding documentation of CURB-65 (34% at baseline, 68% at follow-up) and the collection of lower respiratory tract samples (43% at baseline, 63% at follow-up). CONCLUSION: Our study has demonstrated poor adherence to CAP guidelines at all sites at baseline. After implementing multiple tailored interventions, guideline adherence increased substantially. In conclusion, we recommend that CAP guidelines should be actively adapted in order to be followed in a daily routine.