Short-term respiratory effects of e-cigarettes in healthy individuals and smokers with asthma.

BACKGROUND AND OBJECTIVE: This study investigated the duration of immediate respiratory effects of e-cigarette smoking (ECS) and tested the hypothesis that ECS has more prominent effects in asthmatics compared with healthy smokers (HS). METHODS: Fifty-four smokers, 27 healthy (HS group) and 27 with intermittent asthma (mild asthma (MA) group) underwent a control session (no liquid, no resistor coil inside e-cigarette cartridge) and an experimental session of ECS using standardized puffing settings. Impulse oscillometry impedance (Z), resistance (R), reactance (X) and fractional exhaled nitric oxide (FeNO) were measured before and 0, 15 and 30 min after control and experimental sessions. RESULTS: Control session revealed no significant changes. In the experimental session, immediately post-ECS, both groups exhibited a significant increase in respiratory system total impedance at 5 Hz (Z5) (P < 0.001), respiratory system resistance at 5 Hz (R5) (P < 0.001), respiratory system resistance at 10 Hz (R10) (P < 0.001), respiratory system resistance at 20 Hz (R20) (P < 0.05), resonant frequency (P < 0.001) and reactance area (P < 0.05). MA exhibited higher baseline values and a more prominent effect immediately after ECS compared with HS for Z5 (P = 0.022), R5 (P = 0.010) and R10 (P = 0.013). FeNO decreased significantly in both groups (P < 0.001); HS returned to baseline values in ≤15 min while the MA maintained significantly lower values for an additional 15 min (P < 0.05) and returned to baseline values at 30 min post-ECS. CONCLUSION: A single session of ECS had respiratory mechanical and inflammatory effects, which were more prominent in smokers with asthma.

Home-based maintenance tele-rehabilitation reduces the risk for acute exacerbations of COPD, hospitalisations and emergency department visits.

Pulmonary rehabilitation (PR) remains grossly underutilised by suitable patients worldwide. We investigated whether home-based maintenance tele-rehabilitation will be as effective as hospital-based maintenance rehabilitation and superior to usual care in reducing the risk for acute chronic obstructive pulmonary disease (COPD) exacerbations, hospitalisations and emergency department (ED) visits.Following completion of an initial 2-month PR programme this prospective, randomised controlled trial (between December 2013 and July 2015) compared 12 months of home-based maintenance tele-rehabilitation (n=47) with 12 months of hospital-based, outpatient, maintenance rehabilitation (n=50) and also to 12 months of usual care treatment (n=50) without initial PR.In a multivariate analysis during the 12-month follow-up, both home-based tele-rehabilitation and hospital-based PR remained independent predictors of a lower risk for 1) acute COPD exacerbation (incidence rate ratio (IRR) 0.517, 95% CI 0.389-0.687, and IRR 0.635, 95% CI 0.473-0.853), respectively, and 2) hospitalisations for acute COPD exacerbation (IRR 0.189, 95% CI 0.100-0.358, and IRR 0.375, 95% CI 0.207-0.681), respectively. However, only home-based maintenance tele-rehabilitation and not hospital-based, outpatient, maintenance PR was an independent predictor of ED visits (IRR 0.116, 95% CI 0.072-0.185).Home-based maintenance tele-rehabilitation is equally effective as hospital-based, outpatient, maintenance PR in reducing the risk for acute COPD exacerbation and hospitalisations. In addition, it encounters a lower risk for ED visits, thereby constituting a potentially effective alternative strategy to hospital-based, outpatient, maintenance PR.

Activin A and follistatin in patients with asthma. Does severity make the difference?

BACKGROUND AND OBJECTIVE: Activin A is a pleiotropic cytokine holding a fundamental role in inflammation and tissue remodelling. Follistatin can modulate the bioactivity of activin. We aimed to measure activin A and follistatin in sputum supernatants and bronchoalveolar lavage (BAL) of asthmatic patients and to determine the possible associations with severity as well as with inflammatory and remodelling indices. METHODS: A total of 58 asthmatic patients (33 with severe refractory asthma (SRA)) and 10 healthy controls underwent sputum induction for % cells, activin A, follistatin, eosinophilic cationic protein (ECP), transforming growth factor beta 1 (TGF-ß1), IL-13 and IL-8 measurements. In 22 asthmatic patients, BAL and bronchial biopsies were also performed for the assessment of the above-mentioned variables, measurement of remodelling indices and immunostaining for different activin A receptors. RESULTS: Sputum activin A (pg/mL) was higher in patients with SRA (median (interquartile ranges): 76 (33-185)) compared to mild-to-moderate asthma (44 (18-84); P = 0.005), whereas follistatin did not differ between the two groups. BAL activin A (pg/mL) was higher in patients with SRA compared to those with mild-to-moderate disease. A significant association was observed between activin A and TGF-ß1, eosinophils in sputum and/or in BAL, while reticular basement membrane (RBM) thickness was significantly associated with BAL activin levels only. No difference in immunostaining for activin receptor type IB was observed between patients with SRA and those with mild-to-moderate asthma. CONCLUSION: Sputum and BAL levels of activin A are higher in SRA. The association of activin A with TGF-ß1, eosinophils and RBM thickness may indicate a role of this cytokine in the inflammatory and remodelling process in SRA.

Implication of Interleukin (IL)-18 in the pathogenesis of chronic obstructive pulmonary disease (COPD).

Interleukin (IL)-18 is a pro-inflammatory cytokine that was firstly described as an interferon (IFN)-γ-inducing factor. Similar to IL-1ß, IL-18 is synthesized as an inactive precursor requiring processing by caspase-1 into an active cytokine. The platform for activating caspase-1 is known as the inflammasome, a multiple protein complex. Macrophages and dendritic cells are the primary sources for the release of active IL-18, whereas the inactive precursor remains in the intracellular compartment of mesenchymal cells. Finally, the IL-18 precursor is released from dying cells and processed extracellularly. IL-18 has crucial host defense and antitumor activities, and gene therapy to increase IL-18 levels in tissues protects experimental animals from infection and tumor growth and metastasis. Moreover, multiple studies in experimental animal models have shown that IL-18 over-expression results to emphysematous lesions in mice. The published data prompt to the hypothesis that IL-18 induces a broad spectrum of COPD-like inflammatory and remodeling responses in the murine lung and also induces a mixed type 1, type 2, and type 17 cytokine responses. The majority of studies identify IL-18 as a potential target for future COPD therapeutics to limit both the destructive and remodeling processes occurring in COPD lungs.

Angiopoietins 1 and 2 in sputum supernatant of optimally treated asthmatics: the effect of smoking.

BACKGROUND: 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 optimally treated asthma and to investigate whether smoking represents a significant covariate on the above possible processes. METHODS: Eighty-seven patients with asthma (42 smokers) and 28 healthy subjects (14 smokers) were studied. All subjects underwent lung function tests, bronchial hyper-responsiveness assessment and sputum induction for cell count identification and measurement of Ang-1, Ang-2, vascular endothelial growth factor, TGF-ß1, MMP-2, IL-13, Eosinophilic cationic protein and IL-8 in supernatants. Airway vascular permeability (AVP) index was also assessed. RESULTS: Ang-1 (ng/mL) levels were significantly higher in patients with asthma compared to normal subjects. Smoking significantly increased Ang-1 levels [median, interquartile ranges 24 (13-37) in smoking asthmatics vs 10 (7-14) in nonsmoking asthmatics vs 5·3 (3·7-6·5) and 4·6 (3·8-5·7) in healthy smokers and nonsmokers, respectively, P < 0·001]. Similar results were observed for Ang-2 (pg/mL) [168 (132-203) vs 124 (82-152) vs 94 (78-113) vs 100 (96-108), respectively, P < 0·001]. Regression analysis in the whole study population showed a significant negative association for Ang-1, with AVP index, and MMP-2. Smoking was a significant covariate for both Ang-1 and Ang-2 in asthmatic patients. CONCLUSIONS: Ang-1 and Ang-2 levels are upregulated in patients with optimally treated asthma. Our data support a possible role for smoking in the angiogenetic process in asthma.

Immune response to mycobacterial infection: lessons from flow cytometry.

Detecting and treating active and latent tuberculosis are pivotal elements for effective infection control; yet, due to their significant inherent limitations, the diagnostic means for these two stages of tuberculosis (TB) to date remain suboptimal. This paper reviews the current diagnostic tools for mycobacterial infection and focuses on the application of flow cytometry as a promising method for rapid and reliable diagnosis of mycobacterial infection as well as discrimination between active and latent TB: it summarizes diagnostic biomarkers distinguishing the two states of infection and also features of the distinct immune response against Mycobacterium tuberculosis (Mtb) at certain stages of infection as revealed by flow cytometry to date.

Inflammation and immune response in COPD: where do we stand?

Increasing evidence indicates that chronic inflammatory and immune responses play key roles in the development and progression of COPD. Recent data provide evidence for a role in the NLRP3 inflammasome in the airway inflammation observed in COPD. Cigarette smoke activates innate immune cells by triggering pattern recognition receptors (PRRs) to release "danger signal". These signals act as ligands to Toll-like receptors (TLRs), triggering the production of cytokines and inducing innate inflammation. In smokers who develop COPD there appears to be a specific pattern of inflammation in the airways and parenchyma as a result of both innate and adaptive immune responses, with the predominance of CD8+ and CD4+ cells, and in the more severe disease, with the presence of lymphoid follicles containing B lymphocytes and T cells. Furthermore, viral and bacterial infections interfere with the chronic inflammation seen in stable COPD and exacerbations via pathogen-associated molecular patterns (PAMPs). Finally, autoimmunity is another novel aspect that may play a critical role in the pathogenesis of COPD. This review is un update of the currently discussed roles of inflammatory and immune responses in the pathogenesis of COPD.

Prevalence and Characteristics of Self-Reported Adult Asthma in Cyprus: A Population-Based Observational Study.

Purpose: To estimate the prevalence of asthma in adults, by gender and age, in urban and rural areas of Cyprus. Patients and Methods: This was a population-based, random-digit dialing, telephone nation-wide survey to recruit patients with asthma. Among 8996 random landline-telephone contacted from the five major urban and rural regions of Cyprus, 1914 were finally met the age criterion of ≥18 years old and 572 completed valid screening for prevalence estimation. The participants filled a short screening questionnaire in order for asthma cases to be recognized. Then, asthma cases filled the main ECRHS II questionnaire and were evaluated by a pulmonary physician. All underwent spirometry. Data on demographic characteristics, educational level, profession, smoking status, Body Mass Index (BMI), Total IgE and Eosinophil Cationic Protein levels were measured. Results: The overall prevalence of bronchial asthma in adults in Cyprus was 5.57% (61.1% men and 38.9% women). Among the participants with self-reported bronchial asthma 36.1% were current smokers, while 12.3% were obese (BMI >30). A total value of IgE >115 IU and Eosinophil Cationic Protein (ECP) >20 IU was found in 40% of the participants with established bronchial asthma. Wheezing and chest tightness were the most frequently reported symptoms in asthma patients (36.1% and 34.5%, respectively), while 36.5% experienced at least one exacerbation during the last year. Interestingly, most of the patients were under-treated (14.2% were on maintenance asthma treatment, and 18% used solely reliever medication). Conclusion: This was the first study estimating asthma prevalence in Cyprus. Asthma affects almost 6% of the adult population, with higher prevalence in urban areas and in men compared to women. Interestingly, one-third of the patients were uncontrolled and under-treated. This study revealed that in Cyprus there is space for improvement in the management of asthma.

Pathophysiology of evolution of small airways disease to overt COPD.

BACKGROUND: The slope of phase III (single breath nitrogen test), an index of ventilation inhomogeneity, has been used for early detection of COPD. Tidal airway closure (cyclic opening and closure of the peripheral airways during tidal breathing; AC(T)) and expiratory flow limitation (attainment of maximal expiratory flow during tidal expiration; EFL(T)) cause small airways disease (SAD). The relationships of these indices with COPD severity may reflect the progress from SAD to overt COPD. METHODS: In this cross-sectional study we have assessed for the first time the phase III slope, AC(T) and EFL(T) in 10 smokers with normal spirometry (group O) and 40 COPD patients with GOLD scores from I to IV. RESULTS: In most group O smokers the phase III slope was increased, and further increased with GOLD severity (up to 800%pred in GOLD IV). A close correlation was found of slope with GOLD (r = 0.77). AC(T) was absent in smokers with normal spirometry and in most patients with mild COPD. EFL(T) first appeared in GOLD II patients and its prevalence progressively increased in GOLD III and IV patients. CONCLUSIONS: Most group O smokers exhibit increased phase III. With overt COPD there is a progressive increase in phase III and reduction of FEV(1)/FVC ratio from GOLD I to IV. A reduction of FEV(1) occurs from GOLD stage II. As the disease progresses from moderate to severe, there is an increasing presence of AC(T). Tidal EFL, with dynamic hyperinflation and severe dyspnea is present only in GOLD III and IV.

Physical Activity: A Missing Link in Asthma Care.

Asthma is the commonest respiratory disease and one of unceasingly increasing prevalence and burden. As such, asthma has attracted a major share or scientific interest and clinical attention. With the various clinical and pathophysiological aspects of asthma having been extensively investigated, the important association between asthma and physical activity remains underappreciated and insufficiently explored. Asthma impacts adversely on physical activity. Likewise, poor physical activity may lead to worse asthma outcomes. This concise clinical review presents the current recommendations for physical activity, discusses the available evidence on physical activity in asthma, and examines the causes of low physical activity in adult asthmatic patients. It also reviews the effect of daily physical activity and exercise training on the pathology and clinical outcomes of asthma. Finally, it summarizes the evidence on interventions targeting physical activity in asthma.

Sirtuin 1: Endocan and Sestrin 2 in Different Biological Samples in Patients with Asthma. Does Severity Make the Difference?

BACKGROUND: Sestrin 2, Endocan, and Sirtuin 1 are distinct molecules with some biologic actions associated with asthma pathophysiology. The aim of the present study was to determine the molecular level differences attributable to underlying asthma severity. METHODS: We initially recruited 85 asthmatics with a wide spectrum of severity. All of the patients were optimally treated according to current guidelines. Demographics, test results of lung function, and treatment regimes of all patients were recorded. Sestrin 2, Endocan, and Sirtuin 1 were measured in different biological samples (sputum with two processing methods and serum). RESULTS: A total of 60 patients (35 with severe asthma) were analyzed, since 25 patients failed to produce an adequate sample of sputum. Patients with severe asthma showed significantly higher values for Sestrin 2 [pg/mL], measured in both sputum supernatant and cell pellet, compared to those with mild to moderate asthma [9524 (5696, 12,373) vs. 7476 (4265, 9273) p = 0.029, and 23,748 (15,280, 32,742) vs. 10,084 (3349, 21,784), p = 0.008, respectively]. No other significant differences were observed. No significant associations were observed between biomarkers, inflammatory cells, and lung function. CONCLUSION: Sestrin 2 is increased in patients with severe asthma as part of a mechanism that may modify structural alterations through the imbalance between oxidative stress and antioxidant activity.

Effect of Colchicine vs Standard Care on Cardiac and Inflammatory Biomarkers and Clinical Outcomes in Patients Hospitalized With Coronavirus Disease 2019: The GRECCO-19 Randomized Clinical Trial.

Importance: Severe acute respiratory syndrome coronavirus 2 infection has evolved into a global pandemic. Low-dose colchicine combines anti-inflammatory action with a favorable safety profile. Objective: To evaluate the effect of treatment with colchicine on cardiac and inflammatory biomarkers and clinical outcomes in patients hospitalized with coronavirus disease 2019 (COVID-19). Design, Setting, and Participants: In this prospective, open-label, randomized clinical trial (the Greek Study in the Effects of Colchicine in COVID-19 Complications Prevention), 105 patients hospitalized with COVID-19 were randomized in a 1:1 allocation from April 3 to April 27, 2020, to either standard medical treatment or colchicine with standard medical treatment. The study took place in 16 tertiary hospitals in Greece. Intervention: Colchicine administration (1.5-mg loading dose followed by 0.5 mg after 60 min and maintenance doses of 0.5 mg twice daily) with standard medical treatment for as long as 3 weeks. Main Outcomes and Measures: Primary end points were (1) maximum high-sensitivity cardiac troponin level; (2) time for C-reactive protein to reach more than 3 times the upper reference limit; and (3) time to deterioration by 2 points on a 7-grade clinical status scale, ranging from able to resume normal activities to death. Secondary end points were (1) the percentage of participants requiring mechanical ventilation, (2) all-cause mortality, and (3) number, type, severity, and seriousness of adverse events. The primary efficacy analysis was performed on an intention-to-treat basis. Results: A total of 105 patients were evaluated (61 [58.1%] men; median [interquartile range] age, 64 [54-76] years) with 50 (47.6%) randomized to the control group and 55 (52.4%) to the colchicine group. Median (interquartile range) peak high-sensitivity cardiac troponin values were 0.0112 (0.0043-0.0093) ng/mL in the control group and 0.008 (0.004-0.0135) ng/mL in the colchicine group (P = .34). Median (interquartile range) maximum C-reactive protein levels were 4.5 (1.4-8.9) mg/dL vs 3.1 (0.8-9.8) mg/dL (P = .73), respectively. The clinical primary end point rate was 14.0% in the control group (7 of 50 patients) and 1.8% in the colchicine group (1 of 55 patients) (odds ratio, 0.11; 95% CI, 0.01-0.96; P = .02). Mean (SD) event-free survival time was 18.6 (0.83) days the in the control group vs 20.7 (0.31) in the colchicine group (log rank P = .03). Adverse events were similar in the 2 groups, except for diarrhea, which was more frequent with colchicine group than the control group (25 patients [45.5%] vs 9 patients [18.0%]; P = .003). Conclusions and Relevance: In this randomized clinical trial, participants who received colchicine had statistically significantly improved time to clinical deterioration. There were no significant differences in high-sensitivity cardiac troponin or C-reactive protein levels. These findings should be interpreted with caution. Trial Registration: ClinicalTrials.gov Identifier: NCT04326790.

The lung microbiome dynamics between stability and exacerbation in chronic obstructive pulmonary disease (COPD): Current perspectives.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disorder with a course that is not uniform for all COPD patients. Although smoking is considered as the major cause of the disease, persistent or recurrent infections seem to play a particular role in the disease establishment and progression. COPD is characterized by dysregulated immunity that has been associated with the bacterial colonization and infections. The establishment of culture-independent techniques has shed new light on the relationships between bacterial ecology and health status and expanded our knowledge on the lung microbiome. Interactions between the host and lung microbiome result in inflammation and activation of resident cells. The lung microbiome contains populations of symbionts and pathobionts in balance which lose their equilibrium and disturb the balance of T-helper and regulatory T-cells (Treg) upon infection, or lung disease. In COPD factors such as disease severity, exacerbations, degree of inflammation, and type of treatment used (e.g inhaled or systemic steroids and antibiotics) affect the composition of lung microbiota. Recent data indicate that the presence of specific bacterial taxa in the airways has the potential to influence the host immune response and possibly to interfere with disease phenotype. Although, there is a growing body of evidence for the role of microbiome in COPD several unanswered questions still exist for its clinical relevance.

Serum osteopontin in patients with lung cancer and chronic obstructive pulmonary disease: does the co-existence make the difference?

BACKGROUND: Osteopontin (OPN) is involved in cancer development and metastasis. Increased sputum OPN was detected in chronic obstructive pulmonary disease (COPD). METHODS: We evaluated serum OPN levels in patients with lung cancer (LC) and/or COPD and aimed to determine OPN prognostic performance in 1-year mortality in LC and also its diagnostic performance in LC among COPD patients. We recruited 167 LC patients, 85 with concomitant COPD. 28 COPD patients served as control group. RESULTS: OPN levels were higher in LC compared to COPD alone (P=0.017) and higher in COPD and LC compared to COPD alone (P=0.031). No difference was observed in OPN levels between LC and COPD vs. LC without COPD (P=0.171). Serum OPN ≥50.3 ng/mL was an independent predictor of 1-year mortality in LC. CONCLUSIONS: OPN levels ≥35 ng/mL could predict the presence of LC among COPD patients. In patients with LC and/or COPD, LC is the major determinant for serum OPN. Serum OPN might be a promising prognostic biomarker of LC and a diagnostic biomarker of LC among COPD patients.

Respiratory mechanics in brain injury: A review.

Several clinical and experimental studies have shown that lung injury occurs shortly after brain damage. The responsible mechanisms involve neurogenic pulmonary edema, inflammation, the harmful action of neurotransmitters, or autonomic system dysfunction. Mechanical ventilation, an essential component of life support in brain-damaged patients (BD), may be an additional traumatic factor to the already injured or susceptible to injury lungs of these patients thus worsening lung injury, in case that non lung protective ventilator settings are applied. Measurement of respiratory mechanics in BD patients, as well as assessment of their evolution during mechanical ventilation, may lead to preclinical lung injury detection early enough, allowing thus the selection of the appropriate ventilator settings to avoid ventilator-induced lung injury. The aim of this review is to explore the mechanical properties of the respiratory system in BD patients along with the underlying mechanisms, and to translate the evidence of animal and clinical studies into therapeutic implications regarding the mechanical ventilation of these critically ill patients.

Changes in BODE Quartiles After Pulmonary Rehabilitation Do Not Predict 2-Year Survival in Patients With COPD.

PURPOSE: Pulmonary rehabilitation (PR) has well documented positive effects in patients with chronic obstructive pulmonary disease (COPD). The BODE (body mass index, airflow obstruction, dyspnea, and exercise) index reflects the multicomponent nature of COPD. We aimed to determine whether changes in BODE quartiles after a PR program might affect 2-year survival and which characteristics drive changes in BODE quartiles after PR intervention. METHODS: Ninety-five patients with COPD participated in a PR program. The BODE index and anxiety, depression, and quality of life questionnaires were completed before and after the PR program. Five-year survival was recorded for all patients, irrespective of changes in BODE quartiles. RESULTS: Up to 62% of patients with COPD had an improvement in the BODE index, whereas 42% of patients had a change in BODE quartile. Survival did not differ between patients who did not and who did show an improvement in BODE quartiles, despite a trend in favor of the latter (log-rank P = .202). Similar results were observed for patients who did and did not demonstrate a change in the BODE index ≥2 (log-rank P = .679). Significant changes in BODE quartiles were mainly attributed to the duration of the disease, current smoking status, hospitalization rate in the previous year, and the presence of poorer quality of life, as well as to anxiety and depression at baseline. CONCLUSIONS: Pulmonary rehabilitation significantly influenced the BODE index. The significant changes in BODE quartiles were associated with the duration of the disease, current smoking status, increased hospitalization rate, poorer quality of life, anxiety, and depression at baseline, but failed to predict 2-year survival.

Predictors of future exacerbation risk in patients with asthma.

OBJECTIVES: Although modern treatment of asthma improves asthma control, some patients still experience exacerbations. The aim of the present study was to detect predictors of asthmatic exacerbations Methods: We included patients with asthma followed up in asthma clinics of 2 tertiary University hospitals. Demographic and functional characteristics, levels of exhaled NO, and inflammatory biomarkers (IL-13, ΕCP και IL-8) and cell counts in induced sputum were recorded at baseline. Measurements were performed with the patients in stability and were considered as their personal best. Patients received optimal treatment with good compliance and were followed up for 1 year for asthma exacerbations occurrence. Evaluation of the effect of recorded parameters on asthma exacerbations was performed with univariate and multivariate Poisson regression analysis. RESULTS: 171 patients (118 female) with bronchial asthma (mean age 51.6 ± 13.2 years) were included in the study. The mean number of exacerbations in 1 year of follow up was 0.4 ± 0.8 while the majority of patients (71.9%) did not experience any exacerbation. In multivariate Poisson Regression analysis only 3 characteristics were predictors of future exacerbations: FEV1 [IRR(95% CI)], [0.970(0.954-0.987)], p = 0.001, high BMI [1.078(1.030-1.129)], p = 0.001, and the need for permanent treatment with oral corticosteroids for asthma control maintenance [2.542(1.083-5.964)], p = 0.032 CONCLUSION: Optimal guideline-based asthma management results in minimal occurrence of exacerbations in the majority of patients. Predictors of exacerbations are low FEV1 levels in stability, high BMI and the need for permanent treatment with oral corticosteroids.

Low interleukin (IL)-18 levels in sputum supernatants of patients with severe refractory asthma.

BACKGROUND: Severe refractory asthma (SRA) is characterized by persistent asthma symptoms, amplified airway inflammation despite treatment with high dose inhaled steroids and increased airway bacterial colonization. Interleukin (IL)-18 is a pleiotropic pro-inflammatory cytokine that modulates airway inflammation. Furthermore, as a product of the inflammasome, IL-18 is involved in host defence against viral and bacterial stimuli by modulating the immune response. OBJECTIVE: To determine IL-18 levels in sputum supernatants of patients with asthma and to investigate whether underlying severity affects its levels. Furthermore, possible associations with atopy and mediators and cells involved in the inflammatory process of the airways were examined. METHODS: Forty-five patients with mild intermittent asthma (21 smokers) and 18 patients with SRA in stable state were studied. All subjects underwent lung function tests, skin prick tests, and sputum induction for cell count identification. IL-18 and ECP levels were measured in sputum supernatants. Furthermore, sputum samples were examined for the commonest respiratory pathogens and viruses by real time polymerase chain reaction (RT-PCR). RESULTS: Patients with SRA had significantly lower IL-18 levels in sputum supernatants compared to mild asthmatics (p < 0.001). Twelve out of eighteen patients with SRA were colonized by viruses and/or bacterial pathogens. IL-18 levels correlated with the percentage of macrophages (r = 0.635, p = 0.026) and inversely correlated with the percentage of neutrophils in sputum (r = -0.715, p = 0.009). No correlations were found between IL-18, ECP and the percentage of eosinophils in the sputum of SRA. CONCLUSIONS: In SRA IL-18 is possibly involved in chronic airway inflammation through an eosinophil independent pathway. The decreased levels of IL-18 in SRA support the hypothesis of deregulated inflammasome activation, justifying the susceptibility of these patients for bacterial colonization or infection.