The De Ritis ratio as prognostic biomarker of in-hospital mortality in COVID-19 patients.

Increased concentrations of serum aspartate transaminase (AST) and alanine transaminase (ALT) are common in COVID-19 patients. However, their capacity to predict mortality, particularly the AST/ALT ratio, commonly referred to as the De Ritis ratio, is unknown. We investigated the association between the De Ritis ratio on admission and in-hospital mortality in 105 consecutive patients with coronavirus disease of 2019 (COVID-19) admitted to three COVID-19 referral centres in Sardinia, Italy. The De Ritis ratio was significantly lower in survivors than nonsurvivors (median: 1.25; IQR: 0.91-1.64 vs 1.67; IQR: 1.38-1.97, P = .002) whilst there were no significant between-group differences in ALT and AST concentrations. In ROC curve analysis, the AUC value of the De Ritis ratio was 0.701 (95% CI 0.603-0.787, P = .0006) with sensitivity and specificity of 74% and 70%, respectively. Kaplan-Meier survival curves showed a significant association between the De Ritis ratio and mortality (logrank test P = .014). By contrast, no associations were observed between the ALT and AST concentrations and mortality (logrank test P = .83 and P = .62, respectively). In multivariate Cox regression analysis, the HR in patients with De Ritis ratios ≥1.63 (upper tertile of this parameter) remained significant after adjusting for age, gender, smoking status, cardiovascular disease, intensity of care, diabetes, respiratory diseases, malignancies and kidney disease (HR: 2.46, 95% CI 1.05-5.73, P = .037). Therefore, the De Ritis ratio on admission was significantly associated with in-hospital mortality in COVID-19 patients. Larger studies are required to confirm the capacity of this parameter to independently predict mortality in this group.

Platelet Count and Platelet Indices in Patients with Stable and Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis.

Platelets play an important role in the pathophysiology of chronic obstructive pulmonary disease (COPD) by mediating thrombotic, inflammatory, and immune processes in the lung. We conducted a systematic review and meta-analysis of studies investigating the platelet count and three platelet indices, mean platelet volume (MPV), platelet distribution width (PDW), and platelet to lymphocyte ratio (PLR) in stable COPD vs. non-COPD patients and in stable COPD vs. acute exacerbation of COPD (AECOPD) patients (PROSPERO registration number: CRD42021228263). PubMed, Web of Science, Scopus and Google Scholar were searched from inception to December 2020. Twenty-seven studies were included in the meta-analysis, 26 comparing 4,455 stable COPD patients with 7,128 non-COPD controls and 14 comparing 1,251 stable COPD with 904 AECOPD patients. Stable COPD patients had significantly higher platelet counts (weighted mean difference, WMD = 13.39 x109/L, 95% CI 4.68 to 22.11 x109/L; p < 0.001) and PLR (WMD = 59.52, 95% CI 29.59 to 89.44; p < 0.001) than non-COPD subjects. AECOPD patients had significantly higher PLR values than stable COPD patients (WMD = 46.03, 95% CI 7.70 to 84.35; p = 0.02). No significant differences were observed in MPV and PDW. Between-study heterogeneity was extreme. In sensitivity analysis, the effect size was not modified when each study was sequentially removed. The was no evidence of publication bias. In our meta-analysis, specific platelet biomarkers were associated with stable COPD (platelet count and PLR) and AECOPD (PLR). However, the observed heterogeneity limits the generalizability of the findings. Further studies are required to determine their prognostic utility and the effects of targeted interventions in COPD.

Molecular Epidemiology of the Main Druggable Genetic Alterations in Non-Small Cell Lung Cancer.

Lung cancer is the leading cause of death for malignancy worldwide. Its molecular profiling has enriched our understanding of cancer initiation and progression and has become fundamental to provide guidance on treatment with targeted therapies. Testing the presence of driver mutations in specific genes in lung tumors has thus radically changed the clinical management and outcomes of the disease. Numerous studies performed with traditional sequencing methods have investigated the occurrence of such mutations in lung cancer, and new insights regarding their frequency and clinical significance are continuously provided with the use of last generation sequencing technologies. In this review, we discuss the molecular epidemiology of the main druggable genetic alterations in non-small cell lung cancer, namely EGFR, KRAS, BRAF, MET, and HER2 mutations or amplification, as well as ALK and ROS1 fusions. Furthermore, we investigated the predictive impact of these alterations on the outcomes of modern targeted therapies, their global prognostic significance, and their mutual interaction in cases of co-occurrence.

Methodological Fallacies in the Determination of Serum/Plasma Glutathione Limit Its Translational Potential in Chronic Obstructive Pulmonary Disease.

This study aimed to review and critically appraise the current methodological issues undermining the suitability of the measurement of serum/plasma glutathione, both in the total and reduced form, as a measure of systemic oxidative stress in chronic obstructive pulmonary disease (COPD). Fourteen relevant articles published between 2001 and 2020, in 2003 subjects, 1111 COPD patients, and 892 controls, were reviewed. Nine studies, in 902 COPD patients and 660 controls, measured glutathione (GSH) in the reduced form (rGSH), while the remaining five, in 209 COPD patients and 232 controls, measured total GSH (tGSH). In the control group, tGSH ranged between 5.7 and 7.5 µmol/L, whilst in COPD patients, it ranged between 4.5 and 7.4 µmol/L. The mean tGSH was 6.6 ± 0.9 µmol/L in controls and 5.9 ± 1.4 µmol/L in patients. The concentrations of rGSH in the control group showed a wide range, between 0.47 and 415 µmol/L, and a mean value of 71.9 ± 143.1 µmol/L. Similarly, the concentrations of rGSH in COPD patients ranged between 0.49 and 279 µmol/L, with a mean value of 49.9 ± 95.9 µmol/L. Pooled tGSH concentrations were not significantly different between patients and controls (standard mean difference (SMD) = -1.92, 95% CI -1582 to 0.0219; p = 0.057). Depending on whether the mean concentrations of rGSH in controls were within the accepted normal range of 0.5-5.0 µmol/L, pooled rGSH concentrations showed either a significant (SMD = -3.8, 95% CI -2.266 to -0.709; p < 0.0001) or nonsignificant (SMD = -0.712, 95% CI -0.627 to 0.293; p = 0.48) difference. These results illustrate the existing and largely unaddressed methodological issues in the interpretation of the serum/plasma concentrations of tGSH and rGSH in COPD.

Systemic transsulfuration pathway thiol concentrations in chronic obstructive pulmonary disease patients.

BACKGROUND: It is amply reported that patients with chronic obstructive pulmonary disease (COPD) have increased risk of cardiovascular disease (CVD). Recent evidence suggests that COPD patients have elevated concentrations of plasma homocysteine (Hcy), a transsulfuration pathway analyte that is commonly regarded as a CVD risk factor. DESIGN: We comprehensively investigated the plasma concentrations of transsulfuration pathway analytes, and their relationship with markers of oxidative stress and inflammation, to identify which low molecular thiols might play a pathophysiological role both in CVD and in COPD. Hcy, cysteine (Cys), glutathione (GSH), cysteinylglycine (CysGly), glutamylcysteine (GluCys), taurine (Tau), oxidative stress markers (TBARS and protein-SH, PSH) and the inflammation marker kynurenine/tryptophan (Kyn/Trp) ratio were measured in 54 COPD patients and 54 control subjects. RESULTS: We found increased concentrations of total Hcy (P < .01) and total CysGly (P < .05) in COPD patients when compared to controls. Total Hcy and CysGly were also significantly associated with abnormal lung function parameters and COPD severity. In COPD patients, total Hcy was significantly associated with the Kyn/Trp ratio (P = .0017) whereas total CysGly was significantly associated with both PSH (P = .0298) and the Kyn/Trp ratio (P = <.0001). CONCLUSION: Both total Hcy and CysGly concentrations were significantly associated with the presence and severity of COPD and with markers of oxidative stress (total CysGly) and inflammation (total Hcy and CysGly). This suggests that specific low molecular mass thiols might play a role in the inflammatory and oxidative stress pathways involved in both CVD and COPD.

Blood Cell Count Derived Inflammation Indexes in Patients with Idiopathic Pulmonary Fibrosis.

PURPOSE: Inflammation and immunity play a pivotal but yet unclear role in idiopathic pulmonary fibrosis (IPF), a chronic disorder characterized by progressive damage of lung parenchyma and severe loss of lung function despite optimal treatment. However, the pathophysiological and predictive role of combined blood cell count indexes of inflammation in IPF is uncertain. METHODS: Seventy-three patients with IPF and 62 healthy subjects matched for age, gender and smoking status were included in this cross-sectional study. RESULTS: We found significant differences in neutrophil to lymphocyte ratio (NLR), derived neutrophil to lymphocyte ratio (dNLR), monocyte to lymphocyte ratio (MLR), platelet to lymphocyte ratio (PLR), systemic inflammation response index (SIRI) and aggregate index of systemic inflammation (AISI) between IPF patients and healthy controls. In logistic regression, all combined blood inflammation indexes, barring PLR, were independently associated with the presence of IPF after adjusting for age, gender, body mass index and smoking status. Furthermore, significant associations between FVC% and NLR, LMR, SIRI and AISI, and between DLCO% and NLR, dNLR, LMR, SIRI and AISI, were observed. CONCLUSIONS: In conclusion, our data indicate significant alterations of combined blood cell count indexes of inflammation in IPF.

Biomarkers of Oxidative Stress and Inflammation in Chronic Airway Diseases.

INTRODUCTION: The global burden of chronic airway diseases represents an important public health concern. The role of oxidative stress and inflammation in the pathogenesis of these diseases is well known. The aim of this study is to evaluate the behavior of both inflammatory and oxidative stress biomarkers in patients with chronic bronchitis, current asthma and past asthma in the frame of a population-based study. METHODS: For this purpose, data collected from the Gene Environment Interactions in Respiratory Diseases (GEIRD) Study, an Italian multicentre, multicase-control study, was evaluated. Cases and controls were identified through a two-stage screening process of individuals aged 20-65 years from the general population. Out of 16,569 subjects selected from the general population in the first stage of the survey, 2259 participated in the clinical evaluation. Oxidative stress biomarkers such as 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), 8-isoprostane and glutathione and inflammatory biomarkers such as Fractional Exhaled Nitric Oxide (FENO) and white blood cells were evaluated in 1878 subjects. RESULTS: Current asthmatics presented higher levels of FENO (23.05 ppm), leucocytes (6770 n/µL), basophils (30.75 n/µL) and eosinophils (177.80 n/µL), while subjects with chronic bronchitis showed higher levels of GSH (0.29 mg/mL) and lymphocytes (2101.6 n/µL). The multivariable multinomial logistic regression confirmed high levels of leucocytes (RRR = 1.33), basophils (RRR = 1.48), eosinophils (RRR = 2.39), lymphocytes (RRR = 1.26) and FENO (RRR = 1.42) in subjects with current asthma. Subjects with past asthma had a statistically significant higher level of eosinophils (RRR = 1.78) with respect to controls. Subjects with chronic bronchitis were characterized by increased levels of eosinophils (RRR = 2.15), lymphocytes (RRR = 1.58), GSH (RRR = 2.23) and 8-isoprostane (RRR = 1.23). CONCLUSION: In our study, current asthmatics show a greater expression of the inflammatory profile compared to subjects who have had asthma in the past and chronic bronchitis. On the other hand, chronic bronchitis subjects showed a higher rate of expression of oxidative stress biomarkers compared to asthmatic subjects. In particular, inflammatory markers such as circulating inflammatory cells and FENO seem to be more specific for current asthma, while oxidative stress biomarkers such as glutathione and 8-isoprostane appear to be more specific and applicable to patients with chronic bronchitis.

The Systemic Inflammation Index on Admission Predicts In-Hospital Mortality in COVID-19 Patients.

BACKGROUND: The rapid onset of a systemic pro-inflammatory state followed by acute respiratory distress syndrome is the leading cause of mortality in patients with COVID-19. We performed a retrospective observational study to explore the capacity of different complete blood cell count (CBC)-derived inflammation indexes to predict in-hospital mortality in this group. METHODS: The neutrophil to lymphocyte ratio (NLR), derived NLR (dNLR), platelet to lymphocyte ratio (PLR), mean platelet volume to platelet ratio (MPR), neutrophil to lymphocyte × platelet ratio (NLPR), monocyte to lymphocyte ratio (MLR), systemic inflammation response index (SIRI), systemic inflammation index (SII), and the aggregate index of systemic inflammation (AISI) were calculated on hospital admission in 119 patients with laboratory confirmed COVID-19. RESULTS: Non-survivors had significantly higher AISI, dNLR, NLPR, NLR, SII, and SIRI values when compared to survivors. Similarly, Kaplan-Meier survival curves showed significantly lower survival in patients with higher AISI, dNLR, MLR, NLPR, NLR, SII, and SIRI. However, after adjusting for confounders, only the SII remained significantly associated with survival (HR = 1.0001; 95% CI, 1.0000-1.0001, p = 0.029) in multivariate Cox regression analysis. CONCLUSIONS: The SII on admission independently predicts in-hospital mortality in COVID-19 patients and may assist with early risk stratification in this group.

Recent Advances in Inflammation and Treatment of Small Airways in Asthma.

Small airways were historically considered to be almost irrelevant in the development and control of pulmonary chronic diseases but, as a matter of fact, in the past few years we have learned that they are not so "silent". Asthma is still a worldwide health issue due to the great share of patients being far from optimal management. Several studies have shown that the deeper lung inflammation plays a critical role in asthma pathogenesis, mostly in these not well-controlled subjects. Therefore, assessing the degree of small airways inflammation and impairment appears to be a pivotal step in the asthmatic patient's management. It is now possible to evaluate them through direct and indirect measurements, even if some obstacles still affect their clinical application. The success of any treatment obviously depends on several factors but reaching the deeper lung has become a priority and, for inhaled drugs, this is strictly connected to the molecule's size. The aim of the present review is to summarize the recent evidence concerning the small airway involvement in asthma, its physiopathological characteristics and how it can be evaluated in order to undertake a personalized pharmacological treatment and achieve a better disease control.

The neutrophil-to-lymphocyte ratio as a marker of chronic obstructive pulmonary disease and its exacerbations: A systematic review and meta-analysis.

INTRODUCTION: The main white blood cell populations, neutrophils and lymphocytes, are involved in the pathophysiology of chronic obstructive pulmonary disease (COPD). We conducted a systematic review and meta-analysis of studies investigating the relationship between the neutrophil to lymphocyte ratio (NLR, a marker of subclinical inflammation), presence of COPD, and its exacerbations. METHODS: A comprehensive literature search was conducted in Pubmed, Web of Science and Scopus databases; two investigators independently reviewed suitable studies. RESULTS: Nine studies, from 247 initially identified, were included in the meta-analysis. Seven studies, in 775 COPD patients with stable disease and 496 healthy controls, showed a significant increase in NLR values in stable COPD (standardised mean difference, SMD, 0.773, 95% CI 0.410-1.136; P < 0.001). Furthermore, in six studies in 527 COPD patients with acute exacerbation and 620 COPD patients with stable disease, NLR values were significantly higher in patients with exacerbations (random effects SMD 0.850, 95% CI 0.549-1.151; P < 0.001). CONCLUSIONS: Our meta-analysis showed that NLR values are significantly higher in stable COPD patients when compared to healthy individuals, although the magnitude of the difference is reduced after trim and fill adjustment, and in patients with COPD exacerbations when compared to patients with stable disease. Further studies, in larger cohorts, are needed to confirm whether the NLR is a useful tool in discriminating between COPD patients with stable disease, those with acute exacerbations, and subjects without the disease.

Evaluation of oxidative stress biomarkers in idiopathic pulmonary fibrosis and therapeutic applications: a systematic review.

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF), a fatal lung disease of unknown origin, is characterized by chronic and progressive fibrosing interstitial pneumonia which progressively impairs lung function. Oxidative stress is one of the main pathogenic pathways in IPF. The aim of this systematic review was to describe the type of markers of oxidative stress identified in different biological specimens and the effects of antioxidant therapies in patients with IPF. METHODS: We conducted a systematic search of publications listed in electronic databases (Pubmed, Web of Science, Scopus and Google Scholar) from inception to October 2017. Two investigators independently reviewed all identified articles to determine eligibility. RESULTS: After a substantial proportion of the initially identified articles (n = 554) was excluded because they were duplicates, abstracts, irrelevant, or did not meet the selection criteria, we identified 30 studies. In each study, we critically appraised the type, site (systemic vs. local, e.g. breath, sputum, expired breath condensate, epithelial lining fluid, bronchoalveolar lavage, and lung tissue specimens), and method used for measuring the identified oxidative stress biomarkers. Furthermore, the current knowledge on antioxidant therapies in IPF was summarized. CONCLUSIONS: A number of markers of oxidative stress, with individual advantages and limitations, have been described in patients with IPF. Nevertheless, trials of antioxidant treatments have been unable to demonstrate consistent benefits, barring recent pharmacogenomics data suggesting different results in specific genotype subgroups of patients with IPF.

Systemic concentrations of asymmetric dimethylarginine (ADMA) in chronic obstructive pulmonary disease (COPD): state of the art.

Experimental evidence suggests that oxidative stress (OS) may increase the activity of arginine methylating enzymes that produce the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA). In addition, it is well documented that OS can significantly decrease the synthesis and/or activity of ADMA degrading enzymes, thus causing ADMA accumulation in biological fluids. Recent reports have focused on circulating methylated arginine concentrations in chronic obstructive pulmonary disease, a disease characterized by a significant increase in OS. This review discusses the results of these studies and the opportunities for further research in this area.

Circulating serotonin levels in COPD patients: a pilot study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major and increasing global health problem. Serotonin is a neurotransmitter that participates in several pulmonary functions and it has been involved in oxidative stress, which plays essential roles in the pathogenesis of COPD. The current study aimed at establishing the levels of circulating serotonin in COPD, and investigating eventual relations between serotonin and oxidative stress markers. METHODS: Whole blood serotonin was assessed in 43 consecutive patients with stable COPD and in 43 age and sex-matched healthy controls. RESULTS: Serotonin blood levels were significantly higher in COPD patients than in controls (median 0.81 µmol/L, IQR: 0.61-4.02 vs 0.65 µmol/L, IQR: 0.53-1.39, p = 0.02). The univariate logistic regression analysis evidenced that serotonin levels are independently associated with presence of COPD (crude OR = 7.29, 95% CI: 1.296-41.05, p = 0.003) and such an association was confirmed also after adjusting for several confounders (OR 21.92, 95% CI 2.02-237.83; p = 0.011). CONCLUSIONS: Our study showed higher levels of circulating serotonin in COPD and an inverse correlation with the worsening of airway obstruction. Future studies are necessary to investigate the clinical utility of this finding.

Blood global DNA methylation is decreased in non-severe chronic obstructive pulmonary disease (COPD) patients.

BACKGROUND: Alterations in global DNA methylation have been associated with oxidative stress (OS). Since chronic obstructive pulmonary disease (COPD) is characterized by increased oxidative stress we aimed to evaluate the levels of global DNA methylation in this patient group. METHODS: We assessed methylcytosine (mCyt) levels in DNA from blood collected in 43 COPD patients (29 with mild and 14 with moderate disease) and 43 age- and sex-matched healthy controls. RESULTS: DNA methylation was significantly lower in COPD patients vs. controls (4.20 ± 0.18% mCyt vs. 4.29 ± 0.18% mCyt, p = 0.02). Furthermore, DNA methylation in COPD patients with moderate disease was significantly lower than that in patients with mild disease (4.14 ± 0.15% mCyt vs. 4.23 ± 0.19% mCyt, p < 0.05). Univariate logistic regression analysis showed that lower DNA methylation levels were associated with presence of COPD (crude OR = 0.06, 95% CI 0.00 to 0.67, p = 0.023). This relationship remained significant after adjusting for several confounders (OR 0.03, 95% CI 0.00 to 0.67; p = 0.028). Receiver operating characteristics (ROC) curve analysis demonstrated the area under the curve of mCyt was 0.646, with 46.6% sensitivity and 79.1% specificity for presence of COPD. CONCLUSIONS: There were no significant correlations between methylation and OS indices. The presence and severity of COPD is associated with progressively lower DNA methylation in blood. However, this epigenetic alteration seems independent of oxidative stress.

The relationship between haemoglobin concentrations and obstructive sleep apnea syndrome: A systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis investigates the relationship between haemoglobin (Hb) concentrations and obstructive sleep apnea syndrome (OSAS). METHODS: Following PRISMA guidelines, we searched PubMed, EMBASE, and Cochrane Library from inception to March 8, 2024. Eligible studies included cross-sectional, cohort, and case-control designs comparing Hb concentrations in OSAS patients and healthy controls. Two reviewers independently screened records and extracted data. The risk of bias was assessed using the Joanna Briggs Institute checklist. RESULTS: A total of 27 studies involving 6499 OSAS subjects and 5199 controls were included. Hb concentrations were significantly higher in OSAS patients compared to controls (SMD: 0.28; 95 % CI: 0.18 to 0.39; I2 = 84.4 %). Subgroup analysis by OSAS severity showed that severe OSAS patients had higher Hb concentrations than those with mild/moderate OSAS. Sensitivity analyses confirmed the robustness of the findings. However, 7 studies reported opposite results, indicating possible regional or methodological differences. CONCLUSION: Hb concentrations are elevated in OSAS patients, with higher levels observed in severe cases. The significant heterogeneity and the predominance of studies from Turkey highlight the need for further research in diverse populations. Limitations include potential publication bias and variability in study designs.

A Systematic Review and Meta-Analysis of Mean Platelet Volume and Platelet Distribution Width in Patients with Obstructive Sleep Apnoea Syndrome.

Obstructive sleep apnoea syndrome (OSAS) is a highly prevalent yet underestimated disorder caused by the complete or partial obstruction of the upper airways. Although polysomnography is the gold standard for OSAS diagnosis, there is an active search for easily accessible biomarkers of disease presence and severity, particularly those reflecting morphological changes in specific blood cells. We investigated the associations between the presence and severity of OSAS, continuous positive airway pressure (CPAP) treatment, mean platelet volume (MPV), and platelet distribution width (PDW), routinely assessed as part of the complete blood count. From 262 retrieved records from PubMed, the Web of Science, Scopus, and Google Scholar, 31 manuscripts were selected for a final analysis, 30 investigating MPV and 15 investigating PDW. MPV was not statistically different between OSAS patients and healthy controls; however, it progressively increased with disease severity. By contrast, OSAS patients had significantly higher PDW values than controls (SMD = 0.40, 95% CI: 0.25 to 0.56; p ˂ 0.001), and the difference increased with disease severity. In a univariate meta-regression, there were significant associations between the MPV and publication year, the apnoea-hypopnea index, and diabetes mellitus, while no associations were observed with the PDW. No significant between-group differences were observed in the subgroup analyses. These data suggest that PDW, and to a lesser extent, MPV, are potential biomarkers of OSAS and require further research to ascertain their pathophysiological significance (PROSPERO, CRD42023459413).

Ischemia-Modified Albumin (IMA) Is Associated with Poor Survival in Patients with Newly Diagnosed Idiopathic Pulmonary Fibrosis (IPF): A Pilot Study.

There are increasing efforts to better predict adverse outcomes for idiopathic pulmonary fibrosis (IPF). Our aim was to assess the prognostic potential of ischemia-modified albumin (IMA), an established circulating marker of ischemia and, more recently, oxidative stress, in a cohort of 56 IPF patients recruited between 2015 and 2023 at the University of Sassari, Italy. Demographic and functional parameters and serum IMA concentrations were measured at baseline. Non-survivors had significantly higher IMA concentrations vs. survivors (508 ± 64 vs. 474 ± 42 mABSU, respectively; p = 0.035). The Kaplan-Meier analysis showed a significant association between higher IMA values and poor survival (HR: 3.32, 95% CI from 1.06 to 10.4, p = 0.039). In the Cox regression analysis, this association remained significant after adjusting for the force expiratory volume at 1 s, the total lung capacity, lymphocyte count, and pharmacological treatment (HR: 1.0154, 95% CI from 1.0035 to 1.0275, p = 0.01). IMA, an oxidative stress biomarker measurable using relatively simple and available methods, is independently associated with mortality in IPF. Therefore, its determination may enhance risk stratification and treatment decisions. Prospective studies involving larger cohorts are needed to confirm this association and to endorse the use of IMA in routine practice.

A Systematic Review of the Prognostic Significance of the Body Mass Index in Idiopathic Pulmonary Fibrosis.

The identification of novel prognostic biomarkers might enhance individualized management strategies in patients with idiopathic pulmonary fibrosis (IPF). Although several patient characteristics are currently used to predict outcomes, the prognostic significance of the body mass index (BMI), a surrogate measure of excess fat mass, has not been specifically investigated until recently. We systematically searched PubMed, Web of Science, and Scopus, from inception to July 2022, for studies investigating associations between the BMI and clinical endpoints in IPF. The Joanna Briggs Institute Critical Appraisal Checklist was used to assess the risk of bias. The PRISMA 2020 statement on the reporting of systematic reviews was followed. Thirty-six studies were identified (9958 IPF patients, low risk of bias in 20), of which 26 were published over the last five years. Significant associations between lower BMI values and adverse outcomes were reported in 10 out of 21 studies on mortality, four out of six studies on disease progression or hospitalization, and two out of three studies on nintedanib tolerability. In contrast, 10 out of 11 studies did not report any significant association between the BMI and disease exacerbation. Our systematic review suggests that the BMI might be useful to predict mortality, disease progression, hospitalization, and treatment-related toxicity in IPF (PROSPERO registration number: CRD42022353363).

A Systematic Review and Meta-analysis of Clinical, Respiratory, and Biochemical Risk Factors for Acute Exacerbation of idiopathic Pulmonary Fibrosis.

BACKGROUND: A better capacity to identify patients with idiopathic pulmonary fibrosis (IPF) at risk of acute exacerbation (AEIPF) might improve outcomes and reduce healthcare costs. AIMS: We critically appraised the available evidence of the differences in clinical, respiratory, and biochemical parameters between AEIPF and IPF patients with stable disease (SIPF) by conducting a systematic review and meta-analysis. METHODS: PubMed, Web of Science and Scopus were reviewed up until August 1, 2022, for studies reporting differences in clinical, respiratory, and biochemical parameters (including investigational biomarkers) between AEIPF and SIPF patients. The Joanna Briggs Institute Critical Appraisal Checklist was used to assess the risk of bias. RESULTS: Twenty-nine cross-sectional studies published between 2010 and 2022 were identified (all with a low risk of bias). Of the 32 meta-analysed parameters, significant differences were observed between groups, assessed through standard mean differences or relative ratios, with age, forced vital capacity, vital capacity, carbon monoxide diffusion capacity, total lung capacity, oxygen partial pressure, alveolar-arterial oxygen gradient, P/F ratio, 6 min walk test distance, C-reactive protein, lactate dehydrogenase, white blood cell count, albumin, Krebs von den Lungen 6, surfactant protein D, high mobility group box 1 protein, and interleukin-1ß, 6, and 8. CONCLUSIONS: We identified significant differences between AEIPF and SIPF patients in age and specific parameters of respiratory function, inflammation, and epithelial lung damage. Prospective studies are warranted to determine the capacity of these parameters to predict AEIPF more accurately (PROSPERO registration number: CRD42022356640).