Journal of Clinical Medicine

Research

14 pages, 867 KiB

Open AccessArticle

Neutrophil Percentage-to-Albumin Ratio as a Prognostic Marker in Pneumonia Patients Aged 80 and Above in Intensive Care

by Maside Ari, Aslı Haykir Solay, Tarkan Ozdemir, Murat Yildiz, Oral Mentes, Omer Faruk Tuten, Husra Tetik Manav, Deniz Celik, Melek Doganci, Guler Eraslan Doganay, Emrah Ari and Eren Usul

J. Clin. Med. 2025, 14(9), 3033; https://doi.org/10.3390/jcm14093033 - 28 Apr 2025

Viewed by 164

Abstract

Background/Objectives: In recent years, inflammatory markers have been increasingly utilized to predict disease prognosis. The neutrophil percentage-to-albumin ratio (NPAR) has emerged as a novel biomarker reflecting inflammation and systemic response. This study was conducted to evaluate the prognostic value of NPAR in pneumonia [...] Read more.

Background/Objectives: In recent years, inflammatory markers have been increasingly utilized to predict disease prognosis. The neutrophil percentage-to-albumin ratio (NPAR) has emerged as a novel biomarker reflecting inflammation and systemic response. This study was conducted to evaluate the prognostic value of NPAR in pneumonia patients aged 80 years and older hospitalized in intensive care. Methods: Patients aged 80 years and older who were followed up in the intensive care unit with a diagnosis of pneumonia between 1 October 2022, and 31 May 2024, were retrospectively reviewed. Demographic characteristics, laboratory data, disease severity scores (APACHE II, SOFA), intensive care interventions, and variables associated with mortality were analyzed. NPAR was calculated by dividing the neutrophil percentage by the serum albumin level. The prognostic value of NPAR was assessed using Kaplan–Meier survival analysis, receiver operating characteristic (ROC) curve analysis, and Cox regression analysis. Results: A total of 135 patients were included in the study. Patients with NPAR > 0.286 had significantly higher SOFA (p = 0.002) and APACHE II (p = 0.007) scores. The high NPAR group was at significantly greater risk for requiring invasive mechanical ventilation (p = 0.003), vasopressor support (p = 0.042), and developing sepsis (p = 0.035). Elevated NPAR was strongly associated with mortality (p < 0.001) and was identified as an independent predictor of mortality in the Cox regression analysis (HR = 2.488, 95% CI: 1.167–5.302, p = 0.018). Conclusions: NPAR may serve as an effective biomarker for predicting disease severity and mortality risk in pneumonia patients aged 80 years and older. Due to its simplicity and accessibility, it can be considered a practical parameter for integration into clinical practice. However, large-scale, multicenter, and prospective studies are needed to validate these findings. Full article

(This article belongs to the Special Issue Update on Acute Severe Respiratory Infections)

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9 pages, 219 KiB

Open AccessArticle

Epidemiology and Clinical Relevance of Pneumocystis jirovecii in Non-Human Immunodeficiency Virus Patients at a Tertiary Care Center in Central Europe: A 3-Year Retrospective Study

by Ágnes Jakab, Andrea Harmath, Zoltán Tóth, László Majoros, József Kónya and Renátó Kovács

J. Clin. Med. 2025, 14(8), 2820; https://doi.org/10.3390/jcm14082820 - 19 Apr 2025

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Abstract

Background/Objectives: This study examines the clinical characteristics of Pneumocystis jirovecii pneumonia (PjP) in non-Human immunodeficiency virus (HIV) patients in Hungary to describe its local epidemiological properties. Methods: Our study was conducted at a clinical center with more than 1700 beds at the [...] Read more.

Background/Objectives: This study examines the clinical characteristics of Pneumocystis jirovecii pneumonia (PjP) in non-Human immunodeficiency virus (HIV) patients in Hungary to describe its local epidemiological properties. Methods: Our study was conducted at a clinical center with more than 1700 beds at the University of Debrecen in Hungary. We included all patients without HIV infection for whom a diagnostic evaluation for Pneumocystis infection had been requested between 1 January 2022 and 31 December 2024. Results: In total, 21 cases of PjP were identified from 122 requests at the University of Debrecen Clinical Center between 2022 and 2024. The overall 30-day mortality rate was 43% in PjP. Admission to the intensive care unit (odds ratio [OR] 5.44, 95% confidence interval [CI] 1.87–14.09, p = 0.001), the need for mechanical ventilation (OR 4.09, 95% CI 1.45–12.14, p = 0.015) and hematological malignancies (OR 3.24, 95% CI 1.23–9.18, p = 0.024), were associated with Pneumocystis PCR positivity. Furthermore, a significant association was observed between elevated levels of C-reactive protein (OR 1.01, 95% CI 1–1.01, p = 0.001), 30-day mortality (OR 2.86, 95% CI 1.09–7.92, p = 0.049), and Pneumocystis PCR positivity. Regarding diagnostic platforms used, Fujifilm Wako assay detected serum (1-3)-β-D-glucan positivity (>7 pg/mL) from 352 copies/mL in non-HIV patients with probable PJP. Conclusions: Our study serves as a gap-filling investigation, providing an overview of Pneumocystis epidemiology in the Central European region. Full article

(This article belongs to the Special Issue Update on Acute Severe Respiratory Infections)

17 pages, 1538 KiB

Open AccessArticle

Nebulized Recombinant Tissue Plasminogen Activator (rt-PA) for Acute COVID-19-Induced Respiratory Failure: An Exploratory Proof-of-Concept Trial

by Pratima Chowdary, Banwari Agarwal, Maria Rita Peralta, Sanjay Bhagani, Simon Lee, James Goldring, Marc Lipman, Emal Waqif, Mark Phillips, Helen Philippou, Jonathan H. Foley, Nicola J. Mutch, Robert A. S. Ariëns, Kathleen A. Stringer, Federico Ricciardi, Marie Watissée, Derralynn Hughes, Amit Nathwani, Anne Riddell, David Patch, Jim Buckley, Mark De Neef, Rahul Dimber, Cecilia Diaz-Garcia, Honey Patel, Aarti Nandani, Upuli Dissanayake, Nick Chadwick, Ahmed A. A. M. M. Alkhatip, Peter Watkinson, Eamon Raith, Suveer Singh, Tony Wolff, Rajeev Jha, Simon E. Brill, Ameet Bakhai, Alison Evans, Farhat Gilani and Keith Gomez Show full author list Hide full author list

J. Clin. Med. 2023, 12(18), 5848; https://doi.org/10.3390/jcm12185848 - 8 Sep 2023

Cited by 1 | Viewed by 2192

Abstract

Acute lung injury in COVID-19 results in diffuse alveolar damage with disruption of the alveolar-capillary barrier, coagulation activation, alveolar fibrin deposition and pulmonary capillary thrombi. Nebulized recombinant tissue plasminogen activator (rt-PA) has the potential to facilitate localized thrombolysis in the alveolar compartment and [...] Read more.

Acute lung injury in COVID-19 results in diffuse alveolar damage with disruption of the alveolar-capillary barrier, coagulation activation, alveolar fibrin deposition and pulmonary capillary thrombi. Nebulized recombinant tissue plasminogen activator (rt-PA) has the potential to facilitate localized thrombolysis in the alveolar compartment and improve oxygenation. In this proof-of-concept safety study, adults with COVID-19-induced respiratory failure and a <300 mmHg PaO₂/FiO₂ (P/F) ratio requiring invasive mechanical ventilation (IMV) or non-invasive respiratory support (NIRS) received nebulized rt-PA in two cohorts (C1 and C2), alongside standard of care, between 23 April–30 July 2020 and 21 January–19 February 2021, respectively. Matched historical controls (MHC; n = 18) were used in C1 to explore efficacy. Safety co-primary endpoints were treatment-related bleeds and <1.0–1.5 g/L fibrinogen reduction. A variable dosing strategy with clinical efficacy endpoint and minimal safety concerns was determined in C1 for use in C2; patients were stratified by ventilation type to receive 40–60 mg rt-PA daily for ≤14 days. Nine patients in C1 (IMV, 6/9; NIRS, 3/9) and 26 in C2 (IMV, 12/26; NIRS, 14/26) received nebulized rt-PA for a mean (SD) of 6.7 (4.6) and 9.1(4.6) days, respectively. Four bleeds (one severe, three mild) in three patients were considered treatment related. There were no significant fibrinogen reductions. Greater improvements in mean P/F ratio from baseline to study end were observed in C1 compared with MHC (C1; 154 to 299 vs. MHC; 154 to 212). In C2, there was no difference in the baseline P/F ratio of NIRS and IMV patients. However, a larger improvement in the P/F ratio occurred in NIRS patients (NIRS; 126 to 240 vs. IMV; 120 to 188) and fewer treatment days were required (NIRS; 7.86 vs. IMV; 10.5). Nebulized rt-PA appears to be well-tolerated, with a trend towards improved oxygenation, particularly in the NIRS group. Randomized clinical trials are required to demonstrate the clinical effect significance and magnitude. Full article

(This article belongs to the Special Issue Update on Acute Severe Respiratory Infections)

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15 pages, 675 KiB

Open AccessArticle

Predictors of Length of Stay, Rehospitalization and Mortality in Community-Acquired Pneumonia Patients: A Retrospective Cohort Study

by Giorgia Lüthi-Corridori, Maria Boesing, Andrea Roth, Stéphanie Giezendanner, Anne Barbara Leuppi-Taegtmeyer, Philipp Schuetz and Joerg D. Leuppi

J. Clin. Med. 2023, 12(17), 5601; https://doi.org/10.3390/jcm12175601 - 28 Aug 2023

Cited by 8 | Viewed by 2147

Abstract

Background: Community-acquired pneumonia (CAP) represents one of the leading causes of hospitalization and has a substantial impact on the financial burden of healthcare. The aim of this study was to identify factors associated with the length of hospital stay (LOHS), rehospitalization and mortality [...] Read more.

Background: Community-acquired pneumonia (CAP) represents one of the leading causes of hospitalization and has a substantial impact on the financial burden of healthcare. The aim of this study was to identify factors associated with the length of hospital stay (LOHS), rehospitalization and mortality of patients admitted for CAP. Methods: A retrospective cohort study was conducted with patients presenting to a Swiss public hospital between January 2019 and December 2019. Zero-truncated negative binomial and multivariable logistic regression analyses were performed to assess risk factors. Results: A total of 300 patients were analyzed (median 78 years, IQR [67.56, 85.50] and 53% males) with an average LOHS of 7 days (IQR [5.00, 9.00]). Of the 300 patients, 31.6% (97/300) were re-hospitalized within 6 months, 2.7% (8/300) died within 30 days and 11.7% (35/300) died within 1 year. The results showed that sex (IRR = 0.877, 95% CI = 0.776–0.992, p-value = 0.036), age (IRR = 1.007, 95% CI = 1.002–1.012, p-value = 0.003), qSOFA score (IRR = 1.143, 95% CI = 1.049–1.246, p-value = 0.002) and atypical pneumonia (IRR = 1.357, 95% CI = 1.012–1.819, p-value = 0.04) were predictive of LOHS. Diabetes (OR = 2.149, 95% CI = 1.104–4.172, p-value = 0.024), a higher qSOFA score (OR = 1.958, 95% CI = 1.295–3.002, p-value = 0.002) and rehabilitation after discharge (OR = 2.222, 95% CI = 1.017–4.855, p-value = 0.044) were associated with a higher chance of being re-hospitalized within 6 months, whereas mortality within 30 days and within one year were both associated with older age (OR = 1.248, 95% CI = 1.056–1.562, p-value = 0.026 and OR = 1.073, 95% CI = 1.025–1.132, p-value = 0.005, respectively) and the presence of a cancer diagnosis (OR = 32.671, 95% CI = 4.787–369.1, p-value = 0.001 and OR = 4.408, 95% CI = 1.680–11.43, p-value = 0.002, respectively). Conclusion: This study identified routinely available predictors for LOHS, rehospitalization and mortality in patients with CAP, which may further advance our understanding of CAP and thereby improve patient management, discharge planning and hospital costs. Full article

(This article belongs to the Special Issue Update on Acute Severe Respiratory Infections)

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Review

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24 pages, 979 KiB

Open AccessReview

Role of Respiratory Viruses in Severe Acute Respiratory Failure

by David Mokrani and Jean-François Timsit

J. Clin. Med. 2025, 14(9), 3175; https://doi.org/10.3390/jcm14093175 (registering DOI) - 3 May 2025

Abstract

Respiratory viruses are widespread in the community, affecting both the upper and lower respiratory tract. This review provides an updated synthesis of the epidemiology, pathophysiology, clinical impact, and management of severe respiratory viral infections in critically ill patients, with a focus on immunocompetent [...] Read more.

Respiratory viruses are widespread in the community, affecting both the upper and lower respiratory tract. This review provides an updated synthesis of the epidemiology, pathophysiology, clinical impact, and management of severe respiratory viral infections in critically ill patients, with a focus on immunocompetent adults. The clinical presentation is typically nonspecific, making etiological diagnosis challenging. This limitation has been mitigated by the advent of molecular diagnostics—particularly multiplex PCR (mPCR)—which has not only improved pathogen identification at the bedside but also significantly reshaped our understanding of the epidemiology of respiratory viral infections. Routine mPCR testing has revealed that respiratory viruses are implicated in 30–40% of community-acquired pneumonia hospitalizations and are a frequent trigger of acute decompensations in patients with chronic comorbidities. While some viruses follow seasonal patterns, others circulate year-round. Influenza viruses and Pneumoviridae, including respiratory syncytial virus and human metapneumovirus, remain the principal viral pathogens associated with severe outcomes, particularly acute respiratory failure and mortality. Bacterial co-infections are also common and substantially increase both morbidity and mortality. Despite the growing contribution of respiratory viruses to the burden of critical illness, effective antiviral therapies remain limited. Neuraminidase inhibitors remain the cornerstone of treatment for severe influenza, whereas therapeutic options for other respiratory viruses are largely lacking. Optimizing early diagnosis, refining antiviral strategies, and systematically addressing bacterial co-infections are critical to improving outcomes in patients with severe viral pneumonia. Full article

(This article belongs to the Special Issue Update on Acute Severe Respiratory Infections)

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25 pages, 392 KiB

Open AccessReview

Diagnostic Approach to Pneumonia in Immunocompromised Hosts

by Nadir Ullah, Ludovica Fusco, Luigi Ametrano, Claudia Bartalucci, Daniele Roberto Giacobbe, Antonio Vena, Malgorzata Mikulska and Matteo Bassetti

J. Clin. Med. 2025, 14(2), 389; https://doi.org/10.3390/jcm14020389 - 9 Jan 2025

Viewed by 2824

Abstract

In immunocompromised patients, pneumonia presents a diagnostic challenge due to diverse etiologies, nonspecific symptoms, overlapping radiological presentation, frequent co-infections, and the potential for rapid progression to severe disease. Thus, timely and accurate diagnosis of all pathogens is crucial. This narrative review explores the [...] Read more.

In immunocompromised patients, pneumonia presents a diagnostic challenge due to diverse etiologies, nonspecific symptoms, overlapping radiological presentation, frequent co-infections, and the potential for rapid progression to severe disease. Thus, timely and accurate diagnosis of all pathogens is crucial. This narrative review explores the latest advancements in microbiological diagnostic techniques for pneumonia in immunocompromised patients. It covers major available microbiological tools for diagnosing both community-acquired and hospital-acquired pneumonia, encompassing a wide spectrum of pathogens including bacterial, viral, fungal, and parasitic. While traditional culture methods remain pivotal in identifying many pneumonia-causing etiologies, their limitations in sensitivity and time to results have led to the rise of non-invasive antigen tests and molecular diagnostics. These are increasingly employed alongside cultures and microscopy for more efficient diagnosis, mainly in viral and fungal infections. Lastly, we report the future of pneumonia diagnostics, exploring the potential of metagenomics and CRISPR/Cas13a for more precise and rapid pathogen detection in immunocompromised populations. Full article

(This article belongs to the Special Issue Update on Acute Severe Respiratory Infections)

20 pages, 1957 KiB

Open AccessEditor’s ChoiceReview

Bronchoscopic Diagnosis of Severe Respiratory Infections

by Maire Röder, Anthony Yong Kheng Cordero Ng and Andrew Conway Morris

J. Clin. Med. 2024, 13(19), 6020; https://doi.org/10.3390/jcm13196020 - 9 Oct 2024

Cited by 1 | Viewed by 5941

Abstract

The diagnosis of severe respiratory infections in intensive care remains an area of uncertainty and involves a complex balancing of risks and benefits. Due to the frequent colonisation of the lower respiratory tract in mechanically ventilated patients, there is an ever-present possibility of [...] Read more.

The diagnosis of severe respiratory infections in intensive care remains an area of uncertainty and involves a complex balancing of risks and benefits. Due to the frequent colonisation of the lower respiratory tract in mechanically ventilated patients, there is an ever-present possibility of microbiological samples being contaminated by bystander organisms. This, coupled with the frequency of alveolar infiltrates arising from sterile insults, risks over-treatment and antimicrobial-associated harm. The use of bronchoscopic sampling to obtain protected lower respiratory samples has long been advocated to overcome this problem. The use of bronchoscopy further enables accurate cytological assessment of the alveolar space and direct inspection of the proximal airways for signs of fungal infection or alternative pathologies. With a growing range of molecular techniques, including those based on nucleic acid amplification and even alveolar visualisation and direct bacterial detection, the potential for bronchoscopy is increasing concomitantly. Despite this, there remain concerns regarding the safety of the technique and its benefits versus less invasive sampling techniques. These discussions are reflected in the lack of consensus among international guidelines on the topic. This review will consider the benefits and challenges of diagnostic bronchoscopy in the context of severe respiratory infection. Full article

(This article belongs to the Special Issue Update on Acute Severe Respiratory Infections)

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Other

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13 pages, 2191 KiB

Open AccessCase Report

Severe Bacterial Superinfection of Influenza Pneumonia in Immunocompetent Young Patients: Case Reports

by Szymon Białka, Michał Zieliński, Magdalena Latos, Marlena Skurzyńska, Michał Żak, Piotr Palaczyński and Szymon Skoczyński

J. Clin. Med. 2024, 13(19), 5665; https://doi.org/10.3390/jcm13195665 - 24 Sep 2024

Cited by 3 | Viewed by 2015

Abstract

Influenza can lead to or coexist with severe bacterial pneumonia, with the potential to permanently damage lung tissue, refractory to conservative treatment in the post-COVID-19 period. It can lead to serious complications; therefore, annual vaccinations are recommended. This case series with a literature [...] Read more.

Influenza can lead to or coexist with severe bacterial pneumonia, with the potential to permanently damage lung tissue, refractory to conservative treatment in the post-COVID-19 period. It can lead to serious complications; therefore, annual vaccinations are recommended. This case series with a literature review pertains to two young female patients with an insignificant past medical history, who required emergency lobectomy due to bacterial complications after influenza infection. Urgent lobectomy proves to be a feasible therapeutic option for selected patients with pleural complications. Full article

(This article belongs to the Special Issue Update on Acute Severe Respiratory Infections)

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