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.
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 Ë 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).
Background: The identification of circulating markers of oxidative stress and systemic inflammation might enhance risk stratification in obstructive sleep apnea (OSA). We investigated the association between specific haematological parameters, as easily measurable markers of oxidative stress and inflammation, and the degree of hypoxia during polysomnography using the apnea hypopnea index (AHI), oxygen desaturation index (ODI), and oxygen saturation (SpO2), in OSA patients. Methods: Associations between polysomnographic parameters and demographic, clinical, and laboratory characteristics were assessed in a consecutive series of patients with OSA attending the Respiratory Disease Unit of the University Hospital of Sassari, north Sardinia (Italy), between 2015 and 2019. Results: In 259 OSA patients (195 males and 64 females), the body mass index (BMI) was significantly and positively associated with the AHI and ODI, and negatively associated with the mean SpO2. No haematological parameter was independently associated with the AHI or ODI. By contrast, albumin, neutrophil, and monocyte counts, and the systemic inflammatory response index (SIRI) were independently associated with a lower SpO2. Conclusions: Our results suggest that albumin and specific haematological parameters are promising markers of reduced oxygen saturation in OSA.
Although polysomnography is the gold standard method to diagnose obstructive sleep apnea syndrome (OSAS), there is an ongoing quest for simpler and relatively inexpensive biomarkers of disease presence and severity. To address this issue, we conducted a systematic review of the potential diagnostic role of the red blood cell distribution width (RDW), a routine hematological parameter of red blood cell volume variability, in OSAS. A total of 1478 articles were initially identified in the databases PubMed, Web of Science, Scopus, Embase, and Google Scholar, from their inception to February 2023, and 20 were selected for final analysis. The RDW was significantly higher in OSAS than in non-OSAS subjects (SMD = 0.44, 95% CI 0.20 to 0.67, p < 0.001; low certainty of evidence). In univariate meta-regression, the mean oxygen saturation (SpO2) was significantly associated with the effect size. No significant between-group differences were observed in subgroup analyses. Notably, in OSAS subjects, the RDW SMD progressively increased with disease severity. In conclusion, these results suggest that the RDW is a promising biomarker of OSAS (PROSPERO registration number: CRD42023398047).
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).
Idiopathic Pulmonary Fibrosis , Humans , Cross-Sectional Studies , Disease Progression , Risk Factors , Oxygen
Derived inflammatory indexes from routine hematological parameters might be useful for predicting early-response vs. late/non-response to dupilumab, the first biological agent approved for moderate-to-severe atopic dermatitis (AD). We tested this hypothesis by retrospectively investigating the association between pre-specified baseline inflammatory indexes and dupilumab response (≥50% reduction in the Eczema Area and Severity Index, EASI 50) at 4 and 16 weeks in a consecutive series of 66 AD patients (38 males and 28 females). Forty-six patients (69.7%) were early-responders at 4 weeks, whereas the remaining twenty (30.3%) were late/non-responders at 16 weeks. In logistic regression, the platelet-to-lymphocyte ratio (PLR) was independently associated with early-response (OR = 1.0159, 95% CI 1.0005 to 1.0315, p = 0.0426). The predictive performance of PLR and other derived indexes towards early-response was further improved by their combination with serum IgE concentrations, with a maximum AUC value for the combined systemic immune inflammation index (SII)-IgE of 0.797 (95% CI = 0.677 to 0.884, p < 0.0001). Derived inflammatory indexes, particularly SII-IgE, might be useful to identify early-responders to dupilumab and develop alternative treatment protocols for late/non-responders.
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).
BACKGROUND: Since the beginning of the SARS-CoV-2 pandemic, millions of people have been infected and died. Different therapeutic approaches have been recommended, but only a few have shown clinical advantages. Low-molecular-weight heparin (LMWH) has been recommended to prevent COVID-19-related thrombo-embolic events. We aimed to evaluate the impact of early treatment with LMWH on hospital admission and death in patients with SARS-CoV-2 infection. METHODS: We conducted an observational monocentric retrospective study to evaluate the preventive role of LMWH on the mortality rate of COVID-19 patients. SARS-CoV-2 infected patients were recruited from the beginning of the Italian epidemic to March 31, 2021. We excluded patients with missing data and those chronically exposed to LMWH. Treatment prescription was based on international and national guidelines and modified depending on clinical presentation and drug-drug interactions. RESULTS: Seven hundred thirty-four SARS-CoV-2 infected patients were recruited, with 357 (48.6%) males and a median (IQR) age of 77.9 (65-85.7) years. 77.5% of people developed SARS-CoV-2-related symptoms and 62.8% were admitted to the hospital, and 20.2% died. Four hundred ninety-two (67%) started LMWH. In particular, 296 (40.3%) were treated within five days since symptoms onset. At logistic regression, early LMWH therapy was associated with lower mortality. Furthermore, remdesivir treatment showed a lower risk of death. On the contrary, age, BMI>30 kg/m2, neurological diseases, fever or dyspnea were associated with an increased risk of death. CONCLUSIONS: Early treatment with LMWH was associated with lower mortality in our cohort. Further studies are needed to better assess the role of wider LMWH administration in terms of timing and regimen dose.
COVID-19 , Heparin, Low-Molecular-Weight , Male , Humans , Aged , Aged, 80 and over , Female , Heparin, Low-Molecular-Weight/therapeutic use , Heparin, Low-Molecular-Weight/adverse effects , SARS-CoV-2 , Retrospective Studies , Anticoagulants/therapeutic use
Human serum paraoxonase-1 (PON-1) is a critical antioxidant defence system against lipid oxidation. Decreased PON-1 activity has been associated with systemic oxidative stress in several disease states. We conducted a systematic review and meta-analysis of plasma/serum concentrations of PON-1 in asthma, a chronic inflammatory airway disease. The electronic databases PubMed, Web of Science, Scopus and Google Scholar were searched from inception to February 2022. In total, 8 studies in 355 asthmatic patients and 289 healthy controls were included in the meta-analysis. Serum PON-1 concentrations were significantly lower in asthmatic patients (SMD = -1.58, 95% CI -2.53 to -0.63; p = 0.001). The pooled SMD values were not substantially altered in sensitivity analysis. There was no publication bias. There were non-significant differences in PON-1 concentrations in patients with severe vs. mild-to-moderate asthma (SMD = - 0.39, 95% CI - 1.00 to 0.22, p = 0.21). Our meta-analysis has shown that serum PON-1 concentrations are significantly lower in patients with asthma, suggesting the presence of an impaired antioxidant defense in this group.
Antioxidants , Asthma , Humans , Antioxidants/metabolism , Aryldialkylphosphatase , Oxidative Stress
Patients with chronic obstructive pulmonary disease (COPD) often suffer from other conditions, such as cardiovascular disease, that further increase the risk of adverse outcomes in this group. Serum homocysteine concentrations are positively associated with cardiovascular risk and have also been reported to be increased in COPD. This meta-analysis investigated the association between homocysteine concentrations and COPD. A systematic search of publications in the electronic databases PubMed, Web of Science, Scopus, and Google Scholar, from inception to September 2021, was conducted using the following terms: "Homocysteine" or "Hcy" and "Chronic Obstructive Pulmonary Disease" or "COPD". Weighted mean differences (WMDs) were calculated to evaluate differences in homocysteine concentrations between COPD patients and non-COPD subjects. Risk of bias and certainty of evidence were assessed using the Joanna Briggs Institute Critical Appraisal Checklist and GRADE, respectively. Nine studies in 432 COPD patients (mean age 65 years, 65% males) and 311 controls (mean age 65 years, 56% males) were identified. Pooled results showed that serum homocysteine concentrations were significantly higher in patients with COPD (WMD = 2.91 µmol/L, 95% CI 2.00-3.82 µmol/L; p < 0.001; high certainty of evidence). No publication bias was observed. Our results support the hypothesis that increased homocysteine concentrations are significantly associated with COPD and may account, at least in part, for the increased cardiovascular risk in these patients.
Cardiovascular Diseases , Pulmonary Disease, Chronic Obstructive , Male , Humans , Aged , Female , Quality of Life , Heart
Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are a leading cause of hospitalisation and death in COPD patients. In addition to the identification of better strategies to prevent AECOPD, there is an intense focus on discovering novel markers of disease severity that enhance risk stratification on hospital admission for the targeted institution of aggressive versus supportive treatments. In the quest for such biomarkers, an increasing body of evidence suggests that specific indexes derived from routine complete blood counts, i.e. the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR), can significantly predict adverse outcomes in AECOPD. This narrative review discusses the current evidence regarding the association between the NLR and the PLR on admission and several clinical end-points (need for invasive ventilation, noninvasive mechanical ventilation failure, admission to an intensive care unit, pulmonary hypertension, length of hospitalisation, and mortality) in AECOPD. Future research directions and potential clinical applications of these haematological indexes in this patient group are also discussed.
Neutrophils , Pulmonary Disease, Chronic Obstructive , Humans , Disease Progression , Retrospective Studies , Lymphocytes , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/therapy , Biomarkers
INTRODUCTION: Coronavirus Disease-19 (COVID-19) vaccines reduce the risk of severe disease and mortality. However, the association between vaccination status and number of doses and the PaO2/FiO2 ratio, a clinical measure of hypoxemia associated with an increased risk of intensive care treatment and mortality, has not been investigated. METHODS: We retrospectively assessed a consecutive series of 116 patients admitted to hospital with a primary diagnosis of COVID-19 between January and April 2022. Demographic, clinical, and laboratory data were collected within 24 h from admission. RESULTS: There was a significant positive relationship between the number of vaccine doses and the PaO2/FiO2 ratio (r = 0.223, p = 0.012). This association remained significant after adjusting for confounders. Vaccinated patients had significantly higher PaO2/FiO2 ratios than the unvaccinated (median: 250; IQR: 195-309 vs. 200; IQR: 156-257, p = 0.013). CONCLUSION: These results highlight the importance of the number of vaccine doses received in reducing the degree of hypoxia on admission in hospitalized COVID-19 patients.
The neutrophil-to-lymphocyte ratio (NLR) predicts adverse outcomes in stable chronic obstructive pulmonary disease (COPD); however, its prognostic role in acute exacerbations (AECOPD) is less clear. We conducted a systematic review and meta-analysis of the association between the NLR on admission and adverse outcomes (mortality, need for mechanical ventilation, transfer to the intensive care unit, length of stay, pulmonary hypertension, or their combination) in AECOPD by searching PubMed, Web of Science, and Scopus from inception to April 2022. Risk of bias and certainty of evidence were assessed using the Joanna Briggs Institute Critical Appraisal Checklist and the Grades of Recommendation, Assessment, Development, and Evaluation, respectively. In 15 studies (n = 10,038 patients), the NLR was significantly associated with the risk of adverse outcomes (odds ratio = 1.054, 95% CI 1.016 to 1.093, p = 0.005; low certainty of evidence; standard mean difference = 0.82, 95% CI 0.57 to 1.06, p < 0.001; high certainty of evidence). Pooled sensitivity, specificity, and area under the curve were 0.71 (95% CI 0.64 to 0.77), 0.73 (95% CI 0.65 to 0.80), and 0.78 (95% CI 0.74 to 0.81), respectively. In our study, the NLR on admission was significantly associated with adverse outcomes in AECOPD patients, suggesting the potential utility of this biomarker for early risk stratification and management in this group.
Obstructive sleep apnoea (OSA) is characterized by overproduction of reactive oxygen species and oxidative stress. The antioxidant enzyme paraoxonase-1 (PON-1) may be useful for monitoring the antioxidant defence systems and the effect of treatments in OSA patients. We investigated, by means of systematic review and meta-analysis, the serum concentrations of PON-1 in OSA patients and non-OSA controls. A literature search was conducted in PubMed, Web of Science, Scopus and Google Scholar databases, from the outset to November 2021, utilizing the terms: "paraoxonase" or "PON" or "paraoxonase-1" or "PON-1" and "obstructive sleep apnoea syndrome" or "OSAS" or "OSA". Eleven studies in 429 OSA patients and 258 non-OSA controls were involved in the meta-analysis. The pooled serum PON-1 concentrations were significantly lower in OSA (standardized mean difference (SMD) = -0.70, 95% CI -1.13 to -0.28; p = 0.001). Despite the extreme between-study heterogeneity, the SMD values were not substantially affected by the sequential omission of individual studies. There was no publication bias. Our systematic review and meta-analysis supports the presence of an impaired antioxidant defence system in OSA, possibly the consequence of intermittent hypoxia. Further studies are required to determine the clinical use of PON-1 measurements for risk stratification and monitoring in OSA patients.
BACKGROUND: While a number of individual patient characteristics are associated with survival in idiopathic pulmonary fibrosis (IPF), their incorporation into combined indexes, such as the GAP index, has been shown to increase the predictive capacity. It is unknown whether the predictive capacity of GAP-derived indexes that also include anthropometric and exercise parameters is superior to the original instrument. METHODS: We tested the four-year survival predictive capacity of a modified, adimensional and multiplicative GAP index (IC4) that included percent forced vital capacity (FVC%), diffusing capacity of the lung for carbon monoxide (DLCO%), Body Mass Index (BMI), and six-minute walk distance (6MWD) in 90 IPF patients recruited from two centers in France and Italy. RESULTS: In ROC comparisons, the AUC of the IC4 (0.859, 95% CI 0.770-0.924 P<0.0001) was significantly higher than the AUCs of the individual components, their two-three component combinations, and the original GAP index, with 77% sensitivity and 89% specificity. Mean survival was 14.0±11.7, 23.2±12.7, 34.9±14.8, and 40.8±12.9 months, and survival rate was 0%, 14%, 39% and 73%, in IC4 quartile 1, 2, 3, and 4, respectively. CONCLUSIONS: The IC4, a combined non-dimensional index incorporating FVC%, DLCO%, BMI and 6MWD, provides superior capacity to predict mortality, when compared to its individual components, their other combinations, and the GAP index, in patients with IPF.
Idiopathic Pulmonary Fibrosis , Carbon Monoxide , Humans , Idiopathic Pulmonary Fibrosis/diagnosis , Lung , Survival Rate , Vital Capacity
Chronic obstructive pulmonary disease (COPD) is a progressive disease that is characterized by a state of persistent inflammation and oxidative stress. The presence of oxidative stress in COPD is the result of an imbalance between pro-oxidant and antioxidant mechanisms. The aim of this review was to investigate a possible association between glutathione peroxidase (GPx), a key component of antioxidant defense mechanisms, and COPD. A systematic search for relevant studies was conducted in the electronic databases PubMed, Web of Science, Scopus, and Google Scholar, from inception to June 2021. Standardized mean differences (SMDs) were used to express the differences in GPx concentrations between COPD patients and non-COPD subjects. Twenty-four studies were identified. In 15 studies assessing whole blood/erythrocytes (GPx isoform 1), the pooled results showed that GPx concentrations were significantly lower in patients with COPD (SMD = -1.91, 95% CI -2.55 to -1.28, p < 0.001; moderate certainty of evidence). By contrast, in 10 studies assessing serum/plasma (GPx isoform 3), the pooled results showed that GPx concentrations were not significantly different between the two groups (very low certainty of evidence). The concentration of GPx-1, but not GPx-3, is significantly lower in COPD patients, suggesting an impairment of antioxidant defense mechanisms in this group.
Lipid profile alterations have been observed in patients with coronavirus disease 2019 (COVID-19) in relation to disease severity and mortality. We conducted a systematic review and meta-analysis with meta-regression of studies reporting total, HDL, and LDL-cholesterol, and triglyceride concentrations in hospitalized patients with COVID-19. We searched PubMed, Web of Science and Scopus, between January 2020 and January 2021, for studies describing lipid concentrations, COVID-19 severity, and survival status (PROSPERO registration number: CRD42021253401). Twenty-two studies in 10,122 COVID-19 patients were included in the meta-analysis. Pooled results showed that hospitalized patients with severe disease or non-survivor status had significantly lower total cholesterol (standardized mean difference, SMD = -0.29, 95% CI -0.41 to -0.16, p < 0.001), LDL-cholesterol (SMD = -0.30, 95% CI -0.41 to -0.18, p < 0.001), and HDL-cholesterol (SMD = -0.44, 95% CI -0.62 to -0.26, p < 0.001), but not triglyceride (SMD = 0.04, 95% CI -0.10 to -0.19, p = 0.57), concentrations compared to patients with milder disease or survivor status during follow up. Between-study heterogeneity was large-to-extreme. In sensitivity analysis, the effect size of different lipid fractions was not affected when each study was in turn removed. The Begg's and Egger's t-tests did not show evidence of publication bias, except for studies investigating LDL-cholesterol. In meta-regression, significant associations were observed between the SMD of LDL-cholesterol and age and hypertension, and between the SMD of triglycerides and study endpoint and aspartate aminotransferase. In our systematic review and meta-analysis, lower total, HDL, and LDL-cholesterol, but not triglyceride, concentrations were significantly associated with COVID-19 severity and mortality. Cholesterol concentrations might be useful, in combination with other clinical and demographic variables, for risk stratification and monitoring in this group. Systematic Review Registration: PROSPERO registration number: CRD42021253401.
COVID-19 , Cholesterol , Cholesterol, HDL , Humans , SARS-CoV-2 , Triglycerides
OBJECTIVES/HYPOTHESIS: The aim of this study was to evaluate the correlations between the severity and duration of olfactory dysfunctions (OD), assessed with psychophysical tests, and the viral load on the rhino-pharyngeal swab determined with a direct method, in patients affected by coronavirus disease 2019 (COVID-19). STUDY DESIGN: Prospective cohort study. METHODS: Patients underwent psychophysical olfactory assessment with Connecticut Chemosensory Clinical Research Center test and determination of the normalized viral load on nasopharyngeal swab within 10 days of the clinical onset of COVID-19. RESULTS: Sixty COVID-19 patients were included in this study. On psychophysical testing, 12 patients (20% of the cohort) presented with anosmia, 11 (18.3%) severe hyposmia, 13 (18.3%) moderate hyposmia, and 10 (16.7%) mild hyposmia with an overall prevalence of OD of 76.7%. The overall median olfactory score was 50 (interquartile range [IQR] 30-72.5) with no significant differences between clinical severity subgroups. The median normalized viral load detected in the series was 2.56E+06 viral copies/106 copies of human beta-2microglobulin mRNA present in the sample (IQR 3.17E+04-1.58E+07) without any significant correlations with COVID-19 severity. The correlation between viral load and olfactory scores at baseline (R2 = 0.0007; P = .844) and 60-day follow-up (R2 = 0.0077; P = .519) was weak and not significant. CONCLUSIONS: The presence of OD does not seem to be useful in identifying subjects at risk for being super-spreaders or who is at risk of developing long-term OD. Similarly, the pathogenesis of OD is probably related to individual factors rather than to viral load and activity. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2312-2318, 2021.
Anosmia/diagnosis , COVID-19/complications , SARS-CoV-2/physiology , Severity of Illness Index , Viral Load/statistics & numerical data , Aged , Anosmia/virology , COVID-19/virology , Female , Humans , Male , Middle Aged , Prevalence , Prospective Studies
Oxidative stress induced by nocturnal intermittent hypoxia plays a significant pathophysiological role in obstructive sleep apnea (OSA). Malondialdehyde (MDA), one of the most commonly investigated markers of lipid peroxidation, might assist with the monitoring of oxidative balance in OSA. We conducted a systematic review and meta-analysis to evaluate the differences in circulating MDA concentrations between patients with OSA and non-OSA controls. A systematic search was conducted in the electronic databases Pubmed, Web of Science, Scopus and Google Scholar from inception to December 2020 by using the following terms: "malondialdehyde" or "MDA"; and "Obstructive Sleep Apnea Syndrome", "OSAS" or "OSA". We identified 26 studies in 1223 OSA patients and 716 controls. The pooled MDA concentrations were significantly higher in patients with OSA (standardized mean difference (SMD) 1.43 µmol/L, 95% confidence interval (CI) 1.03 to 1.83 µmol/L, p < 0.001). There was extreme heterogeneity between the studies (I2 = 92.3%, p < 0.001). In meta-regression analysis, the SMD was significantly associated with age, the assay type used and publication year. In our meta-analysis, MDA concentrations were significantly higher in OSA patients than in controls. This finding suggests that MDA, which is a marker of lipid peroxidation, is involved in the pathogenesis of OSA and provides insights for future studies investigating its potential clinical use.
