Airway Inflammation In Patients Research Articles

ATP drives eosinophil effector responses through P2 purinergic receptors

BackgroundEosinophils recognize various stimuli, such as cytokines, chemokines, immunoglobulins, complement, and external pathogens, resulting in their accumulation in mucosal tissues and the progression of inflammation. Eosinophils are also involved in innate Th2-type immune responses mediated through endogenous danger signals, including IL-33, uric acid (UA), or ATP, in non-sensitized mice exposed to environmental allergens. However, the mechanism involved in eosinophil responses to these danger signals remains insufficiently understood. MethodsWe examined migration, adhesion, superoxide production and degranulation of human eosinophils. Isolated eosinophils were incubated with monosodium urate (MSU) crystals and ATPγS, a non-hydrolysable ATP analogue. To determine the involvement of P2 or P2Y2 receptors in eosinophil responses to UA and ATP, eosinophils were preincubated with a pan-P2 receptor inhibitor, oxidized ATP (oATP), or anti-P2Y2 antibody before incubation with MSU crystals or ATPγS. ResultsMSU crystals induced adhesion of eosinophils to recombinant human (rh)-ICAM-1 and induced production of superoxide. oATP abolished eosinophil responses to MSU crystals, suggesting involvement of endogenous ATP and its receptors. Furthermore, exogenous ATP, as ATPγS, induced migration of eosinophils through a model basement membrane, adhesion to rh-ICAM-1, superoxide generation, and degranulation of eosinophil-derived neurotoxin (EDN). oATP and anti-P2Y2 significantly reduced these eosinophil responses. ConclusionsATP serves as an essential mediator of functional responses in human eosinophils. Eosinophil responses to ATP may be implicated in airway inflammation in patients with asthma.

Obstructive sleep apnea exacerbates airway inflammation in patients with chronic obstructive pulmonary disease

BackgroundChronic obstructive pulmonary disease (COPD) concomitant with obstructive sleep apnea (OSA) is known as overlap syndrome. It has an increased rate of hospitalization due to COPD exacerbation which is believed to indicate a worsening of the underlying chronic airway inflammation. Therefore, the aim of this prospective study was to explore whether OSA exacerbates airway inflammation in subjects with COPD by examining the bronchoalveolar lavage (BAL) fluid. MethodsThis prospective study included 47 patients with overlap syndrome and 28 patients with moderate-to-severe stage stable COPD. Twenty-five patients with overlap syndrome adhered to the continuous positive airway pressure (CPAP) treatment; the remaining patients either refused CPAP treatment or discontinued it within two weeks owing to adverse effects or other reasons. BAL fluid was collected from all subjects for the evaluation of cell numbers and tumor necrosis factor alpha (TNFα) and interleukin-8 (IL-8) levels. ResultsThe BAL fluid of patients with overlap syndrome showed a significantly increased proportion of neutrophils and higher TNFα concentration and IL-8 levels than that of COPD patients; however, the serum CRP levels were not significantly different. An association was found between the percentage of neutrophils and the TNFα concentration and IL-8 levels. Moreover, the TNFα concentration was significantly correlated with the percentage of nighttime spent with oxygen saturation less than 90%. After CPAP treatment, airway inflammation was found to decrease significantly. ConclusionsOSA exacerbates airway inflammation in COPD patients. CPAP treatment can improve nocturnal hypoxemia and decrease airway inflammation.

Prevalence of osteopenia and osteoporosis in patients with moderate to severe asthma in Western Canada.

Steroids, inhaled and systemic, are used to treat airway inflammation in patients with asthma; however, steroids are recognized to cause a number of side effects, including osteoporosis. We evaluated the prevalence of osteopenia/osteoporosis in patients with moderate-severe asthma managed through the Edmonton Regional Severe Asthma Centre. We performed a retrospective chart review and analyzed 57 charts on patients with moderate-severe asthma followed through the specialty clinic, and recorded their bone mineral density (BMD). Steroid use was reviewed and the frequency of osteopenia/osteoporosis was compared in patients requiring continuous systemic steroids (Group 1, n=15), intermittent systemic steroids (Group 2, n=15) or inhaled steroids only (Group 3, n=27). The mean age (mean±SD) was 50±14.8 years. Cumulative systemic steroid dose of prednisone equivalent was higher in Group 1 (12.5 mg/day) than Group 2 (3.2 mg/day) (p=0.002). The frequency of osteopenia / osteoporosis was not significantly different between patients in Group 1(67%) and Group 2 (53%, p=0.46) but was significantly greater in patients from Group 1 in comparison with Group 3 (33%, p=0.038). Patients with moderate-severe asthma have a high prevalence of reduced bone density. Many patients treated with intermittent systemic steroids for exacerbations, or who were stable on inhaled steroids, had either osteopenia or osteoporosis before the age of 50. National and international osteoporosis guidelines should emphasize earlier screening for asthma patients; and increase awareness of the detrimental effects of short-term systemic steroids and inhaled steroids on BMD, especially when started at an early age and in northern climates.

Vitamin D reduces eosinophilic airway inflammation in nonatopic asthma

Low levels of vitamin D are associated with asthma severity, airway remodeling, and exacerbation rate increase, especially in nonatopic asthma. Reduced steroid responsiveness or impaired antimicrobial defense might be underlying mechanisms. We sought to evaluate the effect of vitamin D supplementation on eosinophilic and neutrophilic airway inflammation in patients with nonatopic asthma. In a double-blind, randomized, placebo-controlled trial, we investigated the effect of long-acting vitamin D3 (400,000 IU) on sputum neutrophils and eosinophils in 44 patients with nonatopic asthma with neutrophilic (≥53%) and/or eosinophilic (≥3%) airway inflammation. Sputum induction was performed at baseline and after 9 weeks. Other measurements included questionnaires, blood samples, and pulmonary function. Treatment with vitamin D did not significantly affect sputum neutrophils or eosinophils compared with treatment with placebo in the total group. Regarding sputum eosinophils, the effect of vitamin D appeared to be dependent on baseline sputum eosinophil levels (interaction P = .015). In patients with eosinophil levels of 26.2% or more (median in patients with sputum eosinophilia, >3%), eosinophils decreased from a median of 41.0% to 11.8% after vitamin D treatment as compared with an increase from 51.8% to 63.3% in patients receiving placebo (P = .034). Vitamin D treatment also resulted in slightly better Asthma Control Questionnaire scores (P = .08). Vitamin D supplementation reduced eosinophilic airway inflammation in patients with nonatopic asthma with severe eosinophilic airway inflammation, but did not affect sputum neutrophils. Also, a small effect on asthma control was observed. These findings suggest that vitamin D might have potential as an add-on treatment option in eosinophilic asthma.

Cardiovascular and inflammatory effects of simvastatin therapy in patients with COPD: a randomized controlled trial

BackgroundThere is excess cardiovascular mortality in patients with chronic obstructive pulmonary disease. Aortic stiffness, an independent predictor of cardiovascular risk, and systemic and airway inflammation are increased in patients with the disease. Statins modulate aortic stiffness and have anti-inflammatory properties. A proof-of-principle, double-blind, randomized trial determined if 6 weeks of simvastatin 20 mg once daily reduced aortic stiffness and systemic and airway inflammation in patients with chronic obstructive pulmonary disease.MethodsStable patients (n=70) were randomized to simvastatin (active) or placebo. Pre-treatment and post-treatment aortic stiffness, blood pressure, spirometry, and circulating and airway inflammatory mediators and lipids were measured. A predefined subgroup analysis was performed where baseline aortic pulse wave velocity (PWV) was >10 m/sec.ResultsTotal cholesterol dropped in the active group. There was no significant change in aortic PWV between the active group and the placebo group (−0.7 m/sec, P=0.24). In those with aortic stiffness >10 m/sec (n=22), aortic PWV improved in the active group compared with the placebo group (−2.8 m/sec, P=0.03). Neither systemic nor airway inflammatory markers changed.ConclusionThere was a nonsignificant improvement in aortic PWV in those taking simvastatin 20 mg compared with placebo, but in those with higher baseline aortic stiffness (a higher risk group) a significant and clinically relevant reduction in PWV was shown.

The effect of the decoy molecule PA401 on CXCL8 levels in bronchoalveolar lavage fluid of patients with cystic fibrosis

BackgroundThe chemokine interleukin-8 (CXCL8) is a key mediator of inflammation in airways of patients with cystic fibrosis (CF). Glycosaminoglycans (GAGs) possess the ability to influence the chemokine profile of the CF lung by binding CXCL8 and protecting it from proteolytic degradation. CXCL8 is maintained in an active state by this glycan interaction thus increasing infiltration of immune cells such as neutrophils into the lungs. As the CXCL8-based decoy PA401 displays no chemotactic activity, yet demonstrates glycan binding affinity, the aim of this study was to investigate the anti-inflammatory effect of PA401 on CXCL8 levels, and activity, in CF airway samples in vitro. MethodsBronchoalveolar lavage fluid (BALF) was collected from patients with CF homozygous for the ΔF508 mutation (n=13). CXCL8 in CF BALF pre and post exposure to PA401 was quantified by ELISA. Western blot analysis was used to determine PA401 degradation in CF BALF. The ex vivo chemotactic activity of purified neutrophils in response to CF airway secretions was evaluated post exposure to PA401 by use of a Boyden chamber-based motility assay. ResultsExposure of CF BALF to increasing concentrations of PA401 (50–1000pg/ml) over a time course of 2–12h in vitro, significantly reduced the level of detectable CXCL8 (P<0.05). Interestingly, PA401 engendered release of CXCL8 from GAGs exposing the chemokine susceptible to proteolysis. Subsequently, a loss of PA401 was observed (P<0.05) due to proteolytic degradation by elastase like proteases. A 25% decrease in neutrophil chemotactic efficiency towards CF BALF samples incubated with PA401 was also observed (P<0.05). ConclusionPA401 can disrupt CXCL8:GAG complexes, rendering the chemokine susceptible to proteolytic degradation. Clinical application of a CXCL8 decoy, such as PA401, may serve to decrease the inflammatory burden in the CF lung in vivo.

Prediction of Airway Inflammation in Patients with Asymptomatic Asthma by Using Lung Sound Analysis

The intensity and frequency of sounds in a lung sound analysis (LSA) may be related to airway constriction; however, whether any factors of an LSA can predict airway eosinophilic inflammation in patients with asthma is unknown. To determine whether an LSA can predict airway eosinophilic inflammation in patients with asymptomatic asthma. The expiratory-inspiratory ratios of sound power in the low-frequency range (E-I LF) from 36 patients with asymptomatic asthma were compared with those of 14 healthy controls. The relations of E-I LF with airway eosinophilic inflammation were analyzed. The E-I LF cutoff value for predicting airway eosinophilic inflammation also was analyzed. The mean ± SD E-I LF was higher in the patients with asthma and with increased sputum eosinophils than in those patients without increased sputum eosinophils (0.45 ± 0.24 vs 0.20 ± 0.12; P < .001) or in the healthy controls (0.25 ± 0.10; P= .003). A multiple regression analysis showed that the sputum eosinophil ratio and exhaled nitric oxide were independently correlated with E-I LF, P= .0003 and P= .032, respectively. For the prediction of increased sputum eosinophils and increased fractional exhaled nitric oxide levels, the E-I LF thresholds of 0.29 and 0.30 showed sensitivities of 0.80 and 0.74 and specificities of 0.83 and 0.77, respectively. We showed that LSAs can safely predict airway inflammation of patients with asymptomatic asthma.

Sputum neutrophil count after bronchial allergen challenge is related to peripheral blood neutrophil chemotaxis in asthma patients.

The aim of this study was to estimate relations between sputum neutrophilia and the chemotactic activity of peripheral blood neutrophils after the bronchial allergen challenge in asthma patients. Fifteen patients with allergic asthma (AA), 13 patients with allergic rhinitis (AR), all sensitized to Dermatophagoides pteronyssinus, and 8 healthy subjects (HS) underwent bronchial challenge with D. pteronyssinus. Sputum and peripheral blood collection were performed 24h before, 7 and 24h after the bronchial challenge. Cell counts were determined by the May-Grünwald-Giemsa method. Neutrophil chemotaxis was analyzed by a flow cytometer; IL-8 levels were measured by ELISA. Sputum neutrophil count and peripheral blood neutrophil chemotaxis of patients with AA were greater 7 and 24h after the challenge compared with the baseline values and patients with AR and HS (P<0.05). Moreover, a significant correlation was found between the neutrophil count in sputum and IL-8 levels, and the chemotactic activity of peripheral blood neutrophils 24h after the bronchial challenge only the patients with AA (P<0.05). Increased sputum neutrophil count was found to be associated with an enhanced chemotactic activity of peripheral blood neutrophils during allergen-induced late-phase airway inflammation in patients with allergic asthma.

Effects of beclomethason/formoterol and budesonide/formoterol fixed combinations on lung function and airway inflammation in patients with mild to moderate asthma – An exploratory study

RationaleAsthma is a chronic inflammatory airway disease of the whole bronchial tree. In this exploratory study we investigated the effects of beclomethasone/formoterol (becl/form) and budesonide/formoterol (bud/form) fixed combinations on lung function and airway inflammation in patients with mild to moderate asthma. Methods22 adult patients with asthma (mean FEV1 91.6% pred.) were recruited to this prospective phase IV, double-blind, double-dummy, two-way cross-over, single-centre, randomised study. After a 7 days run-in period with bud 200 μg bid patients were randomised to receive 4 weeks of becl/form (100/6 μg) bid in a pressurised metered dose inhaler or bud/form (160/4.5 μg) bid administered via dry powder inhaler. We measured spirometry, bodyplethysmography, impulse oscillometry, nitric oxide (NO) and its alveolar fraction (CAlv), and assessed sputum cellularity. ResultsCAlv significantly decreased after 4 weeks of treatment in each treatment period. The adjusted geometric mean (log transformed data, end of treatment vs. baseline) was 0.942 ppb (95% CI: 0.778–1.141 ppb) for becl/form and 0.903 ppb (95% CI: 0.741–1.099 ppb) for bud/form. Impulse oscillometry revealed a significant decrease in mean Delta R5–R20 of −0.033 kPa * L−1 * sec−1 for becl/form (95% CI: −0.064 to −0.002) and of −0.048 033 kPa * L−1 * sec−1 for bud/form (95% CI: −0.079 to −0.017). Other parameters of lung function and NO showed numerically small and in most cases statistically non-significant changes. ConclusionsIn patients with mild to moderate asthma pre-treated with inhaled corticosteroids, the use of ICS/LABA formulations led to improvements of CAlv and Delta R5–R20 indicating that these parameters might be helpful to further assess the effects of inhaled ICS/LABA combinations on lung function and airway inflammation.

Characterization of airway inflammation in patients with COPD using fractional exhaled nitric oxide levels: a pilot study.

ObjectiveTo characterize fractional exhaled nitric oxide (FeNO) levels that may be indicative of Th2-mediated airway inflammation in patients with chronic obstructive pulmonary disease (COPD).MethodsThis single-visit, outpatient study was conducted in 200 patients aged 40 years and older with COPD. All patients underwent spirometry and FeNO testing. COPD severity was classified according to the Global initiative for chronic Obstructive Lung Disease (GOLD) 2010 guidelines.ResultsPatients who participated in the study had a mean age of 63.9±11.3 years and a mean smoking history of 46±29 pack years. Patients had a mean forced expiratory volume in 1 second % predicted of 53.9%±22.1%. The percentage of patients classified with COPD severity Stage I, II, III, and IV was 13%, 40%, 39%, and 8%, respectively. In addition, according to current procedural terminology codes, 32% of patients were classified as mixed COPD/asthma, 26% as COPD/emphysema, and 42% as all other codes. The mean FeNO level for all patients was 15.3±17.2 parts per billion (ppb). Overall, 89% of patients had a FeNO <25 ppb, 8% had a FeNO 25–50 ppb, and 3% had a FeNO >50 ppb. The percentages of patients with FeNO in the intermediate or high ranges of FeNO were greatest among patients with mixed COPD/asthma (intermediate, 11.5%; high, 6.6%) compared with COPD/emphysema (intermediate, 8%; high, 0) and all other codes (intermediate, 6.3%; high, 1.3%).ConclusionIncreases in FeNO were identified in a subset of patients with COPD, particularly in those previously diagnosed with both COPD and asthma. Since FeNO is useful for identifying patients with airway inflammation who will have a beneficial response to treatment with an inhaled corticosteroid, these data may have important implications for the management of COPD patients.

Effects of an Anti-TSLP Antibody on Allergen-Induced Asthmatic Responses

BackgroundThymic stromal lymphopoietin (TSLP) is an epithelial-cell–derived cytokine that may be important in initiating allergic inflammation. AMG 157 is a human anti-TSLP monoclonal immunoglobulin G2λ that binds human TSLP and prevents receptor interaction.MethodsIn this double-blind, placebo-controlled study, we randomly assigned 31 patients with mild allergic asthma to receive three monthly doses of AMG 157 (700 mg) or placebo intravenously. We conducted allergen challenges on days 42 and 84 to evaluate the effect of AMG 157 in reducing the maximum percentage decrease in the forced expiratory volume in 1 second (FEV1). We also measured the fraction of nitric oxide in exhaled air, blood and sputum eosinophils, and airway hyperresponsiveness. The primary end point was the late asthmatic response, as measured 3 to 7 hours after the allergen challenge.ResultsAMG 157 attenuated most measures of allergen-induced early and late asthmatic responses. The maximum percentage decrease in the FEV1 during the late response was 34.0% smaller in the AMG-157 group than in the placebo group on day 42 (P=0.09) and 45.9% smaller on day 84 (P=0.02). In addition, patients receiving AMG 157 had significant decreases in levels of blood and sputum eosinophils before and after the allergen challenge and in the fraction of exhaled nitric oxide. There were 15 adverse events in the AMG-157 group, as compared with 12 in the placebo group; there were no serious adverse events.ConclusionsTreatment with AMG 157 reduced allergen-induced bronchoconstriction and indexes of airway inflammation before and after allergen challenge. These findings are consistent with a key role for TSLP in allergen-induced airway responses and persistent airway inflammation in patients with allergic asthma. Whether anti-TSLP therapeutics will have clinical value cannot be determined from these data. (Funded by Amgen; ClinicalTrials.gov number, NCT01405963.)

Inflammasomes in Respiratory Disease: From Bench to Bedside

The respiratory tract of human subjects is constantly exposed to harmful microbes and air pollutants. The immune system responds to these offenders to protect the host, but an unbalanced inflammatory response itself may promote tissue damage and ultimately lead to acute and chronic respiratory diseases. Deregulated inflammasome activation is emerging as a key modulator of respiratory infections and pathologic airway inflammation in patients with asthma, COPD, and pulmonary fibrosis. Assembly of these intracellular danger sensors in cells of the respiratory mucosa and alveolar compartment triggers a proinflammatory cell death mode termed pyroptosis and leads to secretion of bioactive IL-1β and IL-18. Here, we summarize and review the inflammasome and its downstream effectors as therapeutic targets for the treatment of respiratory diseases.

Impact of theophylline/corticosteroid combination therapy on sputum hydrogen sulfide levels in patients with COPD

To the Editor: Hydrogen sulfide (H2S) has emerged as a new and important endogenous regulator of inflammation in recent years [1] and may also protect from emphysema induced by cigarette smoke exposure [2]. We have also recently shown that H2S can inhibit airway smooth muscle cell proliferation and inflammatory mediator release in vitro [3]. Serum levels of H2S positively correlate with the decline in lung function in chronic obstructive pulmonary disease (COPD) and were significantly lower in Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage III patients compared with those in GOLD I [4]. Existing therapies for COPD, such as corticosteroids or long-acting anticholinergic agents, may reduce the exacerbation rate but do not significantly slow disease progression. A previous study has shown that theophylline alone had no impact on serum H2S levels and is of limited value in the management of stable COPD [5]. Interestingly, sputum H2S measured in patients with asthma correlated with sputum neutrophil counts and the degree of airflow obstruction measured by forced expiratory volume in 1 s (FEV1) % predicted [6]. Moreover, combination therapy of an inhaled glucocorticoid with low-dose theophylline has been shown to attenuate airway inflammation in patients with COPD and reverse glucocorticoid resistance [7]. We therefore investigated whether the combination of inhaled corticosteroid and low-dose theophylline, as opposed to …

Effect of levofloxacin on neutrophilic airway inflammation in stable COPD: a randomized, double-blind, placebo-controlled trial

RationaleAirway inflammation persists after smoking cessation in established chronic obstructive pulmonary disease (COPD), suggesting that other factors drive the airway inflammatory response.ObjectivesWe tested the hypothesis that high levels of bacterial colonization are associated with increased levels of neutrophilic airway inflammation in stable COPD by examining the cross-sectional relationship between these measurements and by conducting a randomized, double-blind, placebo-controlled study of the effect of levofloxacin in patients with stable COPD.MethodsPatients were randomized to receive either levofloxacin 500 mg daily or placebo for 7 days and underwent sputum induction for a differential cell count and quantitative bacterial analysis at baseline and at days 7, 14, and 28.ResultsSputum percentage neutrophil count correlated with airway bacterial load at baseline (r=0.56; P=0.003). Levofloxacin reduced bacterial load compared with placebo by 4.9-fold (95% confidence interval, 1.4–25.7; P=0.02) at day 7 but had no effect at any point on any marker of neutrophilic airway inflammation. In patients with a baseline bacterial load of more than 106 cfu/mL, levofloxacin treatment was associated with a 26.5% (95% confidence interval, 1.8%–51.3%; P=0.04) greater reduction in the percentage neutrophil count compared with placebo at day 7. Change in percentage neutrophil count correlated significantly with baseline airway bacterial load and change in airway bacterial load.ConclusionIn stable COPD, levofloxacin treatment causes a short-term reduction in bacterial load. This is associated with a reduction in neutrophilic airway inflammation in patients with high bacterial loads. Further studies are required to investigate whether this effect is clinically advantageous.

Is there a role for macrolides in severe asthma?

Severe asthma is a heterogeneous syndrome, encompassing several distinct clinical phenotypes. Different molecular and cellular pathways or endotypes determine the type of underlying airway inflammation in patients with severe asthma, which can be categorized as eosinophilic asthma (allergic and nonallergic) or noneosinophilic asthma (neutrophilic and paucigranulocytic). In this review, we discuss the potential role of macrolides in the treatment of severe asthma in adults. Maintenance treatment with low-dose macrolides such as erythromycin and azithromycin provides clinical benefit in several chronic neutrophilic airway diseases, including cystic fibrosis (CF), non-CF bronchiectasis and exacerbation-prone chronic obstructive pulmonary disease. Although several short-term studies of macrolides in mild-to-moderate asthma have failed to improve lung function, the AzIthromycin in Severe Asthma trial has demonstrated a significant reduction in the rate of exacerbations in patients with exacerbation-prone noneosinophilic severe asthma. As chronic macrolide use is associated with the risks of population antimicrobial resistance, this add-on treatment should be restricted to severe asthma patients at greatest unmet need despite optimal asthma management. Further clinical, translational and basic research is needed to better phenotype patients with severe asthma, to determine the risk-benefit ratio of macrolide maintenance treatment in neutrophilic severe asthma and to elucidate the principal mechanisms of action of macrolides.

Effect of lianhuaqingwen capsules on airway inflammation in patients with acute exacerbation of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is characterized by a chronic inflammatory response that is worsened by acute exacerbations. Lianhuaqingwen (LHQW) has anti-inflammatory and immune regulatory functions and may inhibit the airway inflammation that occurs during an acute exacerbation of COPD. In this study, 100 participants were recruited and randomly assigned, 1 : 1, to the LHQW and the conventional groups, which were treated, respectively, with LHQW capsules and conventional Western medicine or only conventional Western medicine. The scores of the CAT scale and levels of inflammatory cytokines in blood and sputum were measured during treatment. In addition, subjects were subdivided into high-risk and low-risk subgroups. The CAT scores in the LHQW group and high-risk subgroup were clearly improved from the 5th day, but the other groups improved only after treatment was completed. Expression levels of IL-8, TNF-α, IL-17, and IL-23 in the sputum and of IL-8 and IL-17 in the blood were significantly decreased after treatment, and similar results were found in subgroups. These data suggested that LHQW capsules can accelerate the improvement of AECOPD patients, especially for the high-risk subgroup, and the mechanism of action may be related to the decreased release of inflammatory mediators.

Characterization of airway inflammation in patients with COPD using fractional exhaled nitric oxide levels: a pilot study

Characterization of airway inflammation in patients with COPD using fractional exhaled nitric oxide levels: a pilot study

Identification and Validation of Nebulized Aerosol Devices for Sputum Induction

Induced sputum cell counts are a noninvasive and reliable method for evaluating the presence, type and degree of airway inflammation in patients with asthma. Currently, standard nebulizer devices used for sputum induction in multiple patients are labelled as single-patient devices by the manufacturer, which conflicts with infection prevention and control requirements. As such, these devices cannot feasibly be used in a clinical sputum induction program. Therefore, there is a need to identify alternative nebulizer devices that are either disposable or labelled for multipatient use. To apply validated rigorous, scientific testing methods to identify and validate commercially available nebulizer devices appropriate for use in a clinical sputum induction program. Measurement of nebulized aerosol output and size for the selected nebulizer designs followed robust International Organization for Standardization methods. Sputum induction using two of these nebulizers was successfully performed on 10 healthy adult subjects. The cytotechnologist performing sputum cell counts was blinded to the type of nebulizer used. The studied nebulizers had variable aerosol outputs. The AeroNeb Solo (Aerogen, Ireland), Omron NE-U17 (Omron, Japan) and EASYneb II (Flaem Nuova, Italy) systems were found to have similar measurements of aerosol size. There was no significant difference in induced sputum cell results between the AeroNeb Solo and EASYneb II devices. There is a need for rigorous, scientific evaluation of nebulizer devices for clinical applications, including sputum induction, for measurement of cell counts. The present study was the most comprehensive analysis of different nebulizer devices for sputum induction to measure cell counts, and provides a framework for appropriate evaluation of nebulizer devices for induced sputum testing.

Effects of high altitude and cold air exposure on airway inflammation in patients with asthma

AimsEighteen patients with asthma were evaluated during preparation to climb to extreme altitude in order to study the effects of low fractional inspired oxygen (FiO2), prolonged exposure to cold air...

FEATURES OF CYTOKINE PROFILE (IL-4, IL-6, IL-8, IL-10) IN INDUCED SPUTUM IN CHILDREN WITH BRONCHITIS

This article is devoted to the investigation of im­munity system characteristics in children with bronchitis. Analysis of sputum induced by inhalation of hypertonic saline has recently been established as a useful non-invasive technique for measuring airway inflammation in patients. Therefore we used this technique to evaluate the presence of airway and lung inammation in children with the acute bronchitis, pneumonia. Factors of unfavourable prognosis and transformation of bron­chitis into chronic bronchopulmonary diseases including disor­ders ofcytokines production have been determined. 73 patients have been examined in Regional Children Clinical Hospital (RCCH), Kharkiv, Ukrainian. A study was undertaken to deter­mine the airway and lung inammation, by analysing cytokines in the induced sputum from 38 children with acute bronchitis and 38 patients with acute pneumonia. In children with bronchitis sputum levels of interleukin-4 (IL-4), interleukin-6 (IL-6) were statistically signicantly increased in comparison with pneumonia subjects. Local IL-10 levels in sputum were higher in the samples of the pneumonia than in bronchitis. We observed signicant strong correlations between the levels of interleukins in the sputum and levels of the blood immunology cells, the re­verse correlation, which was associated with the dissociation of the immunocompetent cells to the focus airway for the develop­ment of inammatory process with the formation of the cellular and humoral response. The increase of the IL-4, IL-6, IL-8, IL- 10 concentration in the induced sputum of the patients with bronchitis and pneumonia can be used for revealing the risk group of patients with chronic bronchopulmonary diseases.