Elevated peripheral blood monocyte count is associated with prolonged postoperative hospitalization and functional decline in patients with interstitial lung diseases undergoing surgical lung biopsy.

OBJECTIVE: Monocyte count and red cell distribution width (RDW) have shown prognostic potential in patients with fibrotic lung diseases. Their kinetics and prognostic usefulness of peripheral blood indices in patients with interstitial lung diseases (ILDs) undergoing surgical lung biopsy for diagnostic reasons have not been studied. PATIENTS AND METHODS: We retrospectively included consecutive patients with ILD who underwent surgical lung biopsy for diagnostic purposes Between 07/11/2019 and 11/10/2022. RESULTS: Fifty-five (n=55) patients were included in the study. Median age was 65.0 years (95% CI: 63.0 to 66.0). Postoperative peripheral blood monocyte count on Day 1 was significantly higher compared to preoperative, perioperative, and postoperative values on Day 90 (repeated measures ANOVA, p<0.0001). Patients in the high postoperative monocyte count group had significantly increased length of postoperative hospital stay [Mann-Whitney test, p=0.007] and significantly lower Forced Vital Capacity (FVC)% predicted 3 months after surgery [Mann-Whitney test, p=0.029] compared to patients in the low postoperative monocyte count group. Postoperative RDW on Day 90 was significantly higher compared to preoperative, perioperative and postoperative-Day 1 RDW (repeated measures ANOVA, p=0.008, p=0.006, p<0.0001, respectively). Patients in the high postoperative RDW group did not have increased hospital stay (Mann-Whitney test, p=0.49) or decreased FVC% predicted at 3 months compared to patients in the low postoperative RDW group (Mann-Whitney test, p=0.91). CONCLUSIONS: Peripheral blood monocyte count could be a prognostic biomarker for patients with ILDs undergoing diagnostic surgical lung biopsies. RDW does not seem to represent an acute phase biomarker but seems to increase over time following disease progression. Larger studies are urgently required.

Omalizumab for the treatment of allergic rhinitis: a systematic review and meta-analysis.

BACKGROUND: Allergic rhinitis (AR), an IgE mediated inflammatory disease, significantly impacts quality of life of a considerable proportion of the general population. Omalizumab, a humanized monoclonal antibody against IgE, has been evaluated for both seasonal and perennial AR. We aimed to assess the efficacy and safety of omalizumab in randomized controlled trials (RCTs) in inadequately controlled AR. METHODS: We conducted a systematic literature search of RCTs evaluating the safety and efficacy of omalizumab in AR. We synthesized evidence for clinical improvement of AR symptoms, quality of life, reduction of the use of rescue medication, and adverse events. RESULTS: The systematic search returned 289 articles, of which 12 RCTs were eligible for data extraction and meta-analysis. Omalizumab reduced the Daily Nasal Symptom Severity Score (DNSSS) by a summary standardized mean difference of -0.41 points with large heterogeneity; omalizumab significantly reduced the DNSSS both in the 3 cedar pollen-induced AR trials by -0.97 points and to a lower extent in the remaining five non-cedar trials by -0.19 points. Omalizumab also improved the Daily Ocular Symptom Severity Score (DOSSS) by a summary standardized mean difference of -0.30 points with large heterogeneity; the Rhino-conjunctivitis Quality of Life Questionnaire by a summary standardized mean difference of -0.45 points with no heterogeneity and the mean daily consumption of rescue antihistamines by a summary standardized mean difference of -0.21 with large heterogeneity. No statistically significant difference in the occurrence of adverse events was observed between omalizumab and placebo. CONCLUSION: Our findings further support the efficacy and safety of omalizumab in the management of patients with allergic rhinitis inadequately controlled with a conventional treatment.

Stratification of Patients with Chronic Obstructive Pulmonary Disease Using Volatile Organic Compounds.

Chronic obstructive pulmonary disease (COPD) is a common disease that causes long-term disability and death. Its natural history is punctuated by acute worsening of symptoms, called exacerbations, which are associated with increased mortality and hospitalization. In this work, we aim to stratify patients with COPD based on their risk for exacerbation; for this purpose, we employ non-invasive biomarkers, that is, volatile organic compounds (VOCs), acquired from the patients' exhaled breath coupled with their spirometry and age. We utilize a series of classification schemes with the best performing one achieving overall Accuracy = 93.5%. The yielded results are, therefore, encouraging and prompt for further investigation toward the utilization of VOCs in the management of COPD.

[The concept of chronic obstructive pulmonary disease clinical control as a decision - making tool in real clinical practice for optimizing of basic pharmacotherapy].

The main goals of COPD therapy are to achieve clinical stability with minimal clinical manifestations and low risk of relapse. The proposed COPD control concept by analogy with asthma has not been quite well characterized yet. COPD control is defined as "the long - term maintenance of a clinical situation with a low impact of symptoms on the patient's life and absence of exacerbations." The situation of clinical control in COPD is considered desirable and potentially achievable for most patients with COPD. Pharmacotherapeutic options for COPD are constantly expanding. The control concept may be useful when the decision on treatment of COPD is made for dynamic adjustment of the therapy volume.

Clinical, functional and inflammatory characteristics in patients with paucigranulocytic stable asthma: Comparison with different sputum phenotypes.

BACKGROUND: According to induced sputum cell count, four different asthma phenotypes have been recognized (eosinophilic, neutrophilic, mixed and paucigranulocytic). The aim of this study was to detect functional and inflammatory characteristics of patients with paucigranulocytic asthma. METHODS: A total of 240 asthmatic patients were categorized into the four phenotypes according to cell counts in induced sputum. All patients underwent pulmonary function tests, and measurement of fraction of exhaled nitric oxide (FeNO). The levels of IL-8, IL-13 and eosinophilic cationic protein (ECP) were also measured in sputum supernatant. Treatment, asthma control and the presence of severe refractory asthma (SRA) were also recorded. RESULTS: Patients were categorized into the four phenotypes as follows: eosinophilic (40%), mixed (6.7%), neutrophilic (5.4%) and paucigranulocytic (47.9%). Although asthma control test did not differ between groups (P=.288), patients with paucigranulocytic asthma had better lung function (FEV1 % pred) [median (IQR): 71.5 (59.0-88.75) vs 69.0 (59.0-77.6) vs 68.0 (60.0-85.5) vs 80.5 (69.7-95.0), P=.009] for eosinophilic, mixed, neutrophilic and paucigranulocytic asthma, respectively, P=.009). SRA occurred more frequently in the eosinophilic and mixed phenotype (41.6% and 43.7%, respectively) and less frequently in the neutrophilic and paucigranulocytic phenotype (25% and 21.7%, respectively, P=.01). FeNO, ECP and IL-8 were all low in the paucigranulocytic, whereas as expected FeNO and ECP were higher in eosinophilic and mixed asthma, while IL-8 was higher in patients with neutrophilic and mixed asthma (P<.001 for all comparisons). Interestingly, 14.8% of patients with paucigranulocytic asthma had poor asthma control. CONCLUSION: Paucigranulocytic asthma most likely represents a "benign" asthma phenotype, related to a good response to treatment, rather than a "true" phenotype of asthma. However, paucigranulocytic patients that remain not well controlled despite optimal treatment represent an asthmatic population that requires further study for potential novel targeted interventions.

Sputum interleukin-13 as a biomarker for the evaluation of asthma control.

BACKGROUND: Asthma control refers to the extent to which the manifestations of asthma have been reduced or eradicated by treatment. Interleukin-13 (IL-13) has a central role in Th2 response and serves as a possible therapeutic target in uncontrolled asthma. Fraction of exhaled nitric oxide (FeNO) and sputum eosinophils have modest performance in the evaluation of asthma control. OBJECTIVE: To assess the diagnostic performance of sputum IL-13 for the evaluation of asthma control and furthermore to investigate the performance of sputum eosinophils and FeNO. METHODS: One hundred and seventy patients with asthma were studied. All subjects underwent assessment of asthma control by asthma control test (ACT), lung function tests, FeNO measurement and sputum induction for cell count identification and IL-13 measurement in supernatants. RESULTS: IL-13 (pg/mL) levels in sputum supernatant differed significantly among patients with well-controlled asthma and those with not well-controlled asthma [median IQR 78 (66-102) vs. 213 (180-265), P < 0.001]. Receiver operating characteristic (ROC) analysis showed that, for the whole study population, the diagnostic performance of IL-13 was superior to both sputum eosinophils and FeNO levels [area under the curve (AUC) 0.92, 95% CI 0.87 to 0.95 vs. AUC 0.65, 95% CI 0.58 to 0.72 vs. AUC 0.65, 95% CI 0.55 to 0.72, respectively]. CONCLUSION: The diagnostic performance of sputum IL-13 was superior to both sputum eosinophils and FeNO levels for the identification of well-controlled asthma. Sputum IL-13 levels could serve as a useful biomarker for asthma control assessment.

Sputum and BAL Clara cell secretory protein and surfactant protein D levels in asthma.

Clara cell secretory protein (CC16) is associated with Th2 modulation. Surfactant protein D (SPD) plays an important role in surfactant homeostasis and eosinophil chemotaxis. We measured CC16 and SPD in sputum supernatants of 84 asthmatic patients and 12 healthy controls. In 22 asthmatics, we additionally measured CC16 and SPD levels in BAL and assessed smooth muscle area (SMA), reticular basement membrane (RBM) thickness, and epithelial detachment (ED) in bronchial biopsies. Induced sputum CC16 and SPD were significantly higher in patients with severe asthma (SRA) compared to mild-moderate and healthy controls. BAL CC16 and SPD levels were also higher in SRA compared to mild-moderate asthma. CC16 BAL levels correlated with ED, while SPD BAL levels correlated with SMA and RBM. Severity represented a significant covariate for these associations. CC16 and SPD levels are upregulated in SRA and correlate with remodeling indices, suggesting a possible role of these biomarkers in the remodeling process.

Exhaled nitric oxide as screening tool in subjects with suspected asthma without reversibility.

BACKGROUND: As fractional exhaled nitric oxide (FeNO) has been evaluated only in certain settings for asthma diagnosis, we investigated whether FeNO values could predict positive methacholine challenge testing (expressed as PD20) in subjects with suspected asthma but without spirometric reversibility. METHODS: Subjects with asthma-like symptoms and negative bronchodilation test were initially evaluated to undergo FeNO measurement and methacholine bronchial challenge. Diagnostic performance of FeNO to predict PD20 to methacholine <800 µg was examined by constructing receiver-operating characteristic curves. RESULTS: A total of 112 subjects met the inclusion criteria. In all subjects, FeNO >32 ppb was associated with a sensitivity of 0.47 and a specificity of 0.85 for the identification of the PD20 <800 µg (AUC = 0.691, 95% CI = 0.6-0.775, p = 0.00002). In smokers, FeNO >11 ppb was associated with a sensitivity of 0.85 and a specificity of 0.5 for the identification of PD20 <800 µg (AUC = 0.625, 95% CI = 0.45-0.772, p = 0.18), while in atopics a FeNO level >26 ppb was associated with a sensitivity of 0.55 and a specificity of 0.85 (AUC = 0.677, 95% CI = 0.53-0.8, p = 0.02). CONCLUSIONS: In subjects with symptoms compatible with asthma but without spirometric reversibility, specific cutoff levels for FeNO levels significantly predict the positive methacholine challenge, with significant confounding factors being atopy and current smoking.

Levels of prostaglandin E(2) and Cysteinyl-leukotrienes in sputum supernatant of patients with asthma: the effect of smoking.

BACKGROUND: Smoking is associated with worse asthma outcomes and may modify airway inflammation. Such modification may be mediated through an effect on prostaglandin E(2) (PGE(2)) and cysteinyl leukotrienes (Cyst-LTs). OBJECTIVE: We aimed to determine the levels of both PGE(2) and Cyst-LTs in sputum supernatants of patients with asthma and to investigate the effect of smoking habit as well as their associations with inflammatory cells, bronchial hyperresponsiveness (BHR) and lung function. METHODS: Ninety-eight patients to asthma (47 smokers) and 40 healthy subjects (20 smokers) were studied. All subjects underwent sputum induction for cell count identification, PGE(2) and Cyst-LTs levels measurement in supernatants, pulmonary function tests and BHR to methacholine. RESULTS: Patients with asthma had significantly higher levels of both Cyst-LTs and PGE(2) in sputum supernatants compared to healthy subjects [median (interquartile ranges) 432 (287, 575) vs. 91.5 (73.5, 111) pg/mL and 654 (456,789) vs. 117.5 (92,157) pg/mL, respectively, P < 0.001 for both comparisons]. Smoking asthmatics had significantly higher Cyst-LTs and PGE(2) levels compared to non-smoking asthmatics. Cyst-LTs levels in sputum supernatant of smoking asthmatics presented a significant positive association with sputum eosinophils, while PGE(2) levels were positively associated with sputum neutrophils. CONCLUSIONS: The increased concentrations of PGE(2) and Cyst-LTs in sputum supernatants of smoking asthma are consistent with an up-regulation of these two mediators in this specific phenotype of asthma. Furthermore, Cyst-LTs are associated with eosinophilic inflammation, while PGE(2) is associated with the presence of neutrophilic inflammation in smoking asthma.

Work-related respiratory symptoms and airway disease in hairdressers.

BACKGROUND: Hairdressers are occupationally exposed to a number of agents in their workplace that result in respiratory symptoms and changes in pulmonary function. OBJECTIVE: To evaluate associations between occupational exposure and respiratory function and reported symptoms in a group of hairdressers compared to a control group. METHODS: A questionnaire on respiratory symptoms and workplace characteristics was completed by 94 hairdressers and 39 age- and sex-matched controls. Spirometry and exhaled nitric oxide (FeNO) measurements were also performed. RESULTS: Hairdressers reported more severe dyspnea (p=0.03) and eye (p=0.001) and throat (p=0.007) irritation, compared to the control group, at the workplace; no differences were noted at home. Lower FEV1/FVC (p<0.001) and higher FeNO values (p=0.012) were observed in hairdressers. A larger working area and presence of window ventilation were associated with better pulmonary function. CONCLUSION: Worsening of symptoms and pulmonary function at workplace, and alleviating the symptoms at home, indicate that they may be related to occupational exposure.

Increased levels of angiopoietins 1 and 2 in sputum supernatant in severe refractory asthma.

BACKGROUND: Airway and vascular remodeling may play a prominent role in the clinical severity of severe refractory asthma (SRA). Angiopoietin-1 (Ang-1) is an essential mediator of angiogenesis by establishing vascular integrity, whereas angiopoietin-2 (Ang-2) acts as its natural inhibitor. OBJECTIVE: We aimed to determine the levels of angiopoietins in sputum supernatants of patients with SRA and to investigate the possible associations with mediators and cells involved in both the inflammatory and the vascular remodeling processes. METHODS: Thirty-eight patients with SRA, 35 patients with moderate asthma, and 20 healthy subjects were studied. All participants underwent lung function tests, bronchial hyperresponsiveness assessment and sputum induction for cell count identification and Ang-1, Ang-2, VEGF, TGF-ß1, Cys-LTs, MMP-2, IL-13, ECP, and IL-8 measurement in supernatants. Airway vascular permeability (AVP) index was also assessed. RESULTS: Ang-1 (ng/ml) and Ang-2 (pg/ml) levels were significantly elevated in patients with SRA compared with patients with moderate asthma and control subjects [median, interquartile ranges: 30 (17-39) vs 7.5 (5-11) vs 4.7 (3.8-5.9) respectively, P < 0.001; and 506 (400-700) vs 190 (146-236) vs 96 (89-120) respectively, P < 0.001]. Regression analysis showed a significant positive association between Ang-2 and AVP index, MMP-2, Ang-1, and VEGF in SRA. A weak association was also observed between Ang-1 and sputum eosinophils% in SRA. CONCLUSION: Our results indicate that both angiopoietins levels are higher in SRA compared with moderate asthma and healthy subjects. In SRA, Ang-2 is associated with mediators involved in both the inflammatory and the vascular remodeling processes.

Exhaled nitric oxide in asthma in adults: the end is the beginning?

Approximately 20 years after the initial report of the measurement of exhaled nitric oxide (NO) in the exhaled air of humans, numerous publications have evaluated the possible applications of the fraction of exhaled NO (FeNO) in patients with asthma. The aim of the present review is to evaluate the technical issues and confounding factors related to FeNO measurements, as well as the role of FeNO in the diagnosis of asthma, the evaluation of asthmatic patients and the guidance of treatment. Several other issues, including the pursuit for "normal" and best personal values, the prediction of clinically relevant asthma outcomes and the identification of asthma phenotypes and future directions are discussed. FeNO represents the only exhaled biomarker that has reached clinical practice even in primary care settings and this review provides a critical view of the possible applications of this biomarker, both for the basic researcher and the clinician.

The acute effect of smoking in healthy and asthmatic smokers.

BACKGROUND: Acute exposure to cigarette smoke is related to airway and systemic inflammation and oxidative stress. Little is known about the acute effect of cigarette smoking in smoking asthmatics. The aim of this study was to evaluate the acute effect of smoking in airway and systemic inflammation and oxidative stress in normal smokers and patients with properly treated well-controlled persistent asthma. MATERIALS AND METHODS: Ten normal smokers and 10 smokers with moderate persistent asthma controlled with LABA and ICS were recruited. Subjects refrained from smoking for at least 12 h prior to their inclusion. We compared the effects of smoking of two cigarettes on airway obstruction, airway inflammation and oxidative stress [by measuring fraction of exhaled nitric oxide (FeNO), plus pH and 8-isoprostane in exhaled breath condensate (EBC)] before and 30, 90 and 180 min after smoking. Furthermore, we evaluated systemic oxidative stress, C-reactive protein (CRP) and serum amyloid A (SAA) and urine leukotriene E(4) (LTE(4)) before and 180 min after smoking. RESULTS: No differences were observed in EBC pH and 8-isoprostane, FeNO and systemic oxidative stress between the groups at baseline. In asthmatics, EBC pH decreased 30 min and EBC 8-isoprostane increased 90 min after smoking (P = 0.039 and P = 0.029 respectively), which was not evident in smoking controls. Serum oxidative stress increased only in asthmatic smokers at 180 min (P = 0.001). No differences were observed in SAA, CRP and urine LTE(4) levels before and after smoking. CONCLUSION: Acute smoking has more deleterious effects in well-controlled properly treated asthmatic smokers compared with matched normal smokers.

Inflammatory and oxidative stress biomarkers in allergic rhinitis: the effect of smoking.

BACKGROUND: Accumulating evidence confirms the presence of pan-airway inflammation in allergic rhinitis patients. Smoking is known to affect the asthmatic airway inflammation. However, no study has evaluated the impact of smoking on airway inflammation of allergic rhinitis patients. OBJECTIVE: The aim of the present study was to evaluate the impact of smoking on inflammatory and oxidative stress biomarkers in patients with seasonal allergic rhinitis, using non-invasive methods for sample collection. METHODS: Forty patients with seasonal allergic rhinitis (20 smokers and 20 non-smokers) and 30 healthy subjects (15 smokers and 15 non-smokers) were recruited for the study during pollen season. All subjects were submitted to measurement of the fraction of exhaled NO (FeNO), exhaled breath condensate (EBC) collection, nasal lavage collection, pre- and post- bronchodilation spirometry and metacholine bronchial challenge testing. pH, leukotriene B(4) (LTB(4)) and 8-isoprostane were determined in EBC and nasal lavage samples. RESULTS: Patients with allergic rhinitis presented higher LTB(4) and 8-isoprostane levels in nasal lavage (P<0.0001 for both comparisons), with no significant differences between smokers and non-smokers. Patients with allergic rhinitis also presented higher LTB(4) levels and lower pH in EBC (P<0.001 and P=0.004, respectively), with prominent differences between smokers and non-smokers (P<0.0001 and P=0.003, for LTB(4) and pH, respectively). A significant correlation between nasal lavage and EBC LTB(4) values was observed (r(s)=0.313, P=0.048). CONCLUSIONS: Patients with allergic rhinitis present increased LTB(4) and 8-isoprostane in their nasal cavity, however, with no significant differences between smokers and non-smokers. In contrast, smokers with allergic rhinitis present higher LTB(4) levels and lower pH in EBC, suggesting that these patients may be more susceptible to the deleterious effects of smoking, compared with non-smokers.

Epidemiology and clinical significance of mycobacterial respiratory infections in Central Greece.

SETTING: A 750-bed tertiary referral hospital in Central Greece. OBJECTIVE: To determine the incidence of non-tuberculous mycobacteria (NTM) respiratory infection based on the isolation of NTM in respiratory specimens, to study their clinical significance and to evaluate the differences in clinical, radiological and demographic characteristics between patients with lung disease caused by NTM and that caused by Mycobacterium tuberculosis complex (MTC). DESIGN: A 3-year period prospective study to identify patients with positive NTM and MTC respiratory specimens. RESULTS: Between January 2004 and December 2006, 564 positive NTM cultures from 214 patients and 118 MTC cultures from the same number of patients were collected. The incidence rate of clinically significant NTM lung infection was 0.67, 0.54 and 0.94 cases per 100,000 population, and that of MTC infection of the lung was respectively 5.70, 5.28 and 5.10 cases/100,000 in the three study years. Smoking habits and chronic obstructive pulmonary disease were significant risk factors for NTM disease (P < 0.05 and P < 0.001, respectively). CONCLUSIONS: NTM incidence rates were lower than those reported in the rest of Europe and the USA. Further studies are needed to determine the prevalence and the significant geographic variability of NTM and their clinical significance at the national level.

Could IFN-gamma predict the development of residual pleural thickening in tuberculous pleurisy?

BACKGROUND: The aim of our study was to identify predictive factors for the development of residual pleural thickening (RPT) in patients with tuberculous pleurisy (TP). METHODS: A retrospective study of patients with pleural tuberculosis. The clinical and radiological characteristics, and measurements of microbiological and biochemical parameters or markers such as adenosine deaminase (ADA), interferon-gamma (IFN-gamma) and vascular endothelial growth factor (VEGF) in pleural fluid were studied. RESULTS: Thirty one patients (24 male and 7 female) with a mean age of 55.9 years were studied. There were 25 (80.6%) patients with RPT > 2 mm and 6 (19.4%) patients without RPT. Ten patients (32.2%) had RPT > or = 10 mm. The rate of pleural thickening was less in small effusions (p<0.05). IFN-gamma was higher in patients with RPT > or = 10 mm (p < 0.05) in comparison with those with RPT < 10 mm. CONCLUSIONS: Pleural fluid IFN-gamma may deserve further investigation in order to build up preventive and therapeutic strategies against RPT and its clinical complications.

Exhaled breath condensate in patients with asthma: implications for application in clinical practice.

Exhaled breath condensate (EBC) analysis, a rather appealing and promising method, can be used to evaluate conveniently and non-invasively a wide range of molecules from the respiratory tract, and to understand better the pathways propagating airway inflammation. A large number of mediators of inflammation, including adenosine, ammonia, hydrogen peroxide, isoprostanes, leukotrienes, prostanoids, nitrogen oxides, peptides and cytokines, have been studied in EBC. Concentrations of such mediators have been shown to be related to the underlying asthma and its severity and to be modulated by therapeutic interventions. Despite the encouraging positive results to date, the introduction of EBC in everyday clinical practice requires the resolution of some methodological pitfalls, the standardization of EBC collection and finally the identification of a reliable biomarker that is reproducible has normal values and provides information regarding the underlying inflammatory process and the response to treatment. So far, none of the parameters studied in EBC fulfils the aforementioned requirements with one possible exception: pH. EBC pH is reproducible, has normal values, reflects a significant part of asthma pathophysiology and is measurable on-site with standardized methodology although some methodological aspects of measurement of pH in EBC (e.g. the effect of ambient CO(2), sample de-aeration, time for pH measurement) require further research. However, EBC pH has not been evaluated prospectively as a guide for treatment, in a manner similar to exhaled NO and sputum eosinophils. EBC represents a simple and totally non-invasive procedure that may contribute towards our understanding of asthma pathophysiology. Besides the evaluation of new biomarkers, the standardization of the already existing procedures is warranted for the introduction of EBC in clinical practice.

Serum vascular endothelial growth factor is related to systemic oxidative stress in patients with lung cancer.

Vascular endothelial growth factor (VEGF) is known to play crucial role in tumour angiogenesis. It is demonstrated that VEGF can be up-regulated by oxidative stress. The aim of this study was to determine the serum VEGF levels and oxidative stress in patients with primary lung cancer and to investigate their association with clinicopathologic factors. We measured serum VEGF levels and oxidative stress in 63 patients (age 63.02+/-1.12 S.E.M.) with primary lung cancer before any treatment (39 NSCLC and 24 SCLC; 6 patients stage I, 3 stage II, 25 stage III and 29 stage IV) and 25 normal subjects. The serum VEGF levels were measured with enzyme linked immunosorbent assay. Serum oxidative stress levels were detected by a commercially available assay (D-ROMs test, Diacron, Grossetto, Italy). The levels of oxidative stress in patients were higher than those in normal subjects (555.3+/-30.35 UCarr vs. 360.1+/-17.46 UCarr). Additionally, a significant difference was found in serum VEGF levels between lung cancer patients and healthy control subjects (428.1+/-38.42pg/ml vs. 298.8+/-19.89pg/ml, respectively, p=0.040). Interestingly, serum oxidative stress presented a significant correlation with serum VEGF levels in patients with lung cancer (r=0.542, p=0.002). Serum VEGF levels were significantly associated with the clinical staging (N-stage) of the patients (p=0.023), performance status (p=0.004) and age (p=0.004). In conclusion, oxidative stress and VEGF are significantly increased in patients with primary lung cancer. The correlation between them might implicate new aspects of the mechanisms controlling tumour angiogenesis and may present clinical interest in the future. Further studies are warranted to evaluate the role of oxidative stress and VEGF as possible biomarkers for the diagnosis and follow-up of patients with lung cancer.