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 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).

Evaluation of Inflammation and Oxidative Stress Markers in Patients with Obstructive Sleep Apnea (OSA).

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.

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).

Long-term residential exposure to air pollution and risk of chronic respiratory diseases in Italy: The BIGEPI study.

Long-term exposure to air pollution has adverse respiratory health effects. We investigated the cross-sectional relationship between residential exposure to air pollutants and the risk of suffering from chronic respiratory diseases in some Italian cities. In the BIGEPI project, we harmonised questionnaire data from two population-based studies conducted in 2007-2014. By combining self-reported diagnoses, symptoms and medication use, we identified cases of rhinitis (n = 965), asthma (n = 328), chronic bronchitis/chronic obstructive pulmonary disease (CB/COPD, n = 469), and controls (n = 2380) belonging to 13 cohorts from 8 Italian cities (Pavia, Turin, Verona, Terni, Pisa, Ancona, Palermo, Sassari). We derived mean residential concentrations of fine particulate matter (PM10, PM2.5), nitrogen dioxide (NO2), and summer ozone (O3) for the period 2013-2015 using spatiotemporal models at a 1 km resolution. We fitted logistic regression models with controls as reference category, a random-intercept for cohort, and adjusting for sex, age, education, BMI, smoking, and climate. Mean ± SD exposures were 28.7 ± 6.0 µg/m3 (PM10), 20.1 ± 5.6 µg/m3 (PM2.5), 27.2 ± 9.7 µg/m3 (NO2), and 70.8 ± 4.2 µg/m3 (summer O3). The concentrations of PM10, PM2.5, and NO2 were higher in Northern Italian cities. We found associations between PM exposure and rhinitis (PM10: OR 1.62, 95%CI: 1.19-2.20 and PM2.5: OR 1.80, 95%CI: 1.16-2.81, per 10 µg/m3) and between NO2 exposure and CB/COPD (OR 1.22, 95%CI: 1.07-1.38 per 10 µg/m3), whereas asthma was not related to environmental exposures. Results remained consistent using different adjustment sets, including bi-pollutant models, and after excluding subjects who had changed residential address in the last 5 years. We found novel evidence of association between long-term PM exposure and increased risk of rhinitis, the chronic respiratory disease with the highest prevalence in the general population. Exposure to NO2, a pollutant characterised by strong oxidative properties, seems to affect mainly CB/COPD.

Association between Red Blood Cell Distribution Width and Obstructive Sleep Apnea Syndrome: A Systematic Review and Meta-Analysis.

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).

Blood Cells Count Derived Inflammation Indexes as Predictors of Early Treatment Response to Dupilumab in Patients with Moderate-to-Severe Atopic Dermatitis.

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.

Relationship of long-term air pollution exposure with asthma and rhinitis in Italy: an innovative multipollutant approach.

BACKGROUND: air pollution is a complex mixture; novel multipollutant approaches could help understanding the health effects of multiple concomitant exposures to air pollutants. AIM: to assess the relationship of long-term air pollution exposure with the prevalence of respiratory/allergic symptoms and diseases in an Italian multicenter study using single and multipollutant approaches. METHODS: 14420 adults living in 6 Italian cities (Ancona, Pavia, Pisa, Sassari, Turin, Verona) were investigated in 2005-2011 within 11 different study cohorts. Questionnaire information about risk factors and health outcomes was collected. Machine learning derived mean annual concentrations of PM10, PM2.5, NO2 and mean summer concentrations of O3 (µg/m3) at residential level (1-km resolution) were used for the period 2013-2015. The associations between the four pollutants and respiratory/allergic symptoms/diseases were assessed using two approaches: a) logistic regression models (single-pollutant models), b) principal component logistic regression models (multipollutant models). All the models were adjusted for age, sex, education level, smoking habits, season of interview, climatic index and included a random intercept for cohorts. RESULTS: the three-year average (± standard deviation) pollutants concentrations at residential level were: 20.3 ± 6.8 µg/m3 for PM2.5, 29.2 ± 7.0 µg/m3 for PM10, 28.0 ± 11.2 µg/m3 for NO2, and 70.9 ± 4.3 µg/m3 for summer O3. Through the multipollutant models the following associations emerged: PM10 and PM2.5 were related to 14-25% increased odds of rhinitis, 23-34% of asthma and 30-33% of night awakening; NO2 was related to 6-9% increased odds of rhinitis, 7-8% of asthma and 12% of night awakening; O3 was associated with 37% increased odds of asthma attacks. Overall, the Odds Ratios estimated through the multipollutant models were attenuated when compared to those of the single-pollutant models. CONCLUSIONS: this study enabled to obtain new information about the health effects of air pollution on respiratory/allergic outcomes in adults, applying innovative methods for exposure assessment and multipollutant analyses.

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 paraoxonase-1 activity in asthma.

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.

A systematic review and meta-analysis of homocysteine concentrations in chronic obstructive pulmonary disease.

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.

[The role of exposure to airborne pollutants in the workplace on the prevalence and severity of chronic respiratory disease in Italy]. / Il ruolo dell'esposizione a inquinanti aerodispersi nel luogo di lavoro sulla prevalenza e gravità della malattia respiratoria cronica in Italia.

OBJECTIVES: occupational exposure to vapours, gases, dusts and fumes (VGDF) plays an important role in the development and exacerbation of respiratory diseases. The aim of this study is to evaluate the possible association of occupational exposure to airborne pollutants and chronic respiratory diseases. DESIGN: multicase-control study. SETTING AND PARTICIPANTS: cases of chronic respiratory diseases and controls from the Italian multicentric study Gene Environment Interaction in Respiratory Diseases (GEIRD). MAIN OUTCOME MEASURES: the occurrence of rhinitis, asthma, chronic bronchitis/chronic obstructive pulmonary disease (COPD), asthma severity, spirometry data, exhaled nitric oxide (FeNO) were examined in relation to chronic and acute occupational exposures to airborne pollutants using multiple regression models. RESULTS: 2,943 subjects were enrolled in the study. Regularm exposure to VGDF was associated with a higher prevalence of chronic bronchitis/COPD (OR 1.40, 95%CI 0.98-1.99), especially in those also having asthma (OR 1.80, 95%CI 1.14-2.85), a lower prevalence of remittent asthma (OR 0.53, 95%CI 0.29-0.96) and, in those with asthma, an increased activity of the disease (severity score) (OR 1.77, 95%CI 1.20-2.60). No associations were observed between occupational exposure and prevalence of rhinitis, spirometry and FeNO data. Finally, an association was found between acute exposure to airborne pollutants (occupational and non-occupational) and the respiratory diseases investigated, in particular active asthma and asthma associated chronic bronchitis/BPCO. CONCLUSIONS: these data confirm a significant role of occupational exposure to airborne pollutants on respiratory health, underlying the importance of workplace exposure prevention, in particular for more susceptible subjects, as those with respiratory diseases.

Comparison of Clinical Features, Complete Blood Count Parameters, and Outcomes between Two Distinct Waves of COVID-19: A Monocentric Report from Italy.

BACKGROUND: Since the beginning of the SARS-CoV-2 pandemic, the ability to predict the trajectory of the disease has represented a major challenge for clinicians. There is recent evidence that complete blood cell count (CBC)-derived inflammation indexes have predictive value in COVID-19. We aimed to describe any changes in the clinical features, CBC-derived ratios, and outcomes of patients admitted to our hospital across two temporally distinct waves. METHODS: We retrospectively assessed and compared the clinical characteristics and blood cell count values of patients hospitalized during the second and fourth waves of COVID-19, and explored any outcome differences in terms of the level of respiratory support required and transfer to intensive care. RESULTS: We observed that fourth-wave patients were older, less male-predominant, and carried more comorbidities compared to the second-wave patients but, nevertheless, experienced more favorable outcomes. A strong internal correlation was documented for both waves between outcomes and CBC-derived ratios, with the fourth-wave cases displaying lower admission values of the neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), platelet-to-lymphocyte ratio (PLR), and systemic inflammation index (SII). No significant differences were found for lymphocyte-to-monocyte ratio (LMR), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI). CONCLUSIONS: We observed that both admission values of CBC-derived indexes and adverse respiratory outcomes decreased from the second to the fourth wave of COVID-19. These data represent a contribution to the existing knowledge on the role of CBC-derived indexes as a potential tool to help clinicians to quickly differentiate in-hospital patients at increased risk of serious illness and death.

The Association of Self-Reported Birthweight with Lung Function and Respiratory Diseases: Results from a Multi-Centre, Multi-Case Control Study in Italy.

Early life conditions are associated with lung function and the development of respiratory and non-respiratory illnesses. The relationship with birthweight (BW), however, is conflicting. We examined associations of self-reported BW with lung function and the development of respiratory and also non-respiratory diseases within the GEIRD (Gene-Environment Interaction in Respiratory Diseases) project, an Italian multi-centre, multi-case control study involving cases of COPD, asthma, allergic rhinitis and controls. Multinomial logistic regression was performed with case/control status as response variable; BW as main determinant; and adjusting for sex, age and smoking status. Of the 2287 participants reporting BW, 6.4% (n = 147) had low BW (<2500 g), and this proportion was greater in women than men (7.8% vs. 5.1%; p = 0.006). Both men and women with low BW were shorter than those with normal BW (mean ± SD: 160.2 ± 5.5 vs. 162.6 ± 6.5 cm in women, p = 0.009; 172.4 ± 6.1 vs. 174.8 ± 7.2 cm in men, p < 0.001). Although FEV1 and FVC were reduced in individuals with low BW, this was explained by associations with sex and height. In multivariable analysis, BW was not associated with respiratory diseases in adulthood. However, those with low BW had a higher risk of self-reported hospitalisation for lung disease before the age of two (10.3% vs. 4.1%; p < 0.001), severe respiratory infection before the age of five (16.9% vs. 8.8%; p = 0.001) and hypertension in adulthood (29.9% vs. 23.7%; p = 0.001); however, they had a lower risk of arrhythmia (2.7% vs. 5.8%; p = 0.027).

Clinical significance of the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in acute exacerbations of COPD: present and future.

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.

Vaccination Status and Number of Vaccine Doses Are Independently Associated with the PaO2/FiO2 Ratio on Admission in Hospitalized COVID-19 Patients.

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.

Predictors of Malignancy in Patients With Haemoptysis

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A Comprehensive Systematic Review and Meta-Analysis of the Association between the Neutrophil-to-Lymphocyte Ratio and Adverse Outcomes in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

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.

Paraoxonase-1 Concentrations in Obstructive Sleep Apnoea: A Systematic Review and Meta-Analysis.

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.