Sputum Neutrophil Counts Research Articles

Pentraxin 3 sputum levels differ in patients with chronic obstructive pulmonary disease vs asthma

BackgroundImmune response has been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD) and asthma. Pentraxin 3 (PTX3) is a multifunctional pattern recognition protein and an important component of the innate immune system that can be assessed in blood and induced sputum. ObjectiveTo determine whether PTX3 measured in induced sputum could discriminate patients with COPD from patients with asthma. MethodsA cross-sectional study of 68 participants (27 with COPD, 25 with asthma, and 16 healthy controls) was performed. At study inclusion sputum was collected and total and differential cell numbers and PTX3 levels were determined. ResultsPentraxin 3 was detected in 89% of patients with COPD, 56% of patients with asthma, and 19% of controls (P = .001). It discriminated participants with COPD (24.6 ng/mL, 0–384 ng/mL) from controls (0 ng/mL, 0–36 ng/mL, P < .001) and from participants with asthma (1.2 ng/mL, 0–100 ng/mL, P = .01; area under the receiver operating curve 0.82 [0.71–0.94]). Regression analyses determined that sputum PTX3 and neutrophil counts were independently associated with COPD. In addition, PTX3 levels were independently associated with COPD severity. ConclusionPentraxin 3 sputum levels are increased in patients with COPD and has good power to discriminate these patients from patients with asthma and healthy individuals.

Airway bacteria measured by quantitative polymerase chain reaction and culture in patients with stable COPD: relationship with neutrophilic airway inflammation, exacerbation frequency, and lung function.

BackgroundPotentially pathogenic microorganisms can be detected by quantitative real-time polymerase chain reaction (qPCR) in sputum from patients with COPD, although how this technique relates to culture and clinical measures of disease is unclear. We used cross-sectional and longitudinal data to test the hypotheses that qPCR is a more sensitive measure of bacterial presence and is associated with neutrophilic airway inflammation and adverse clinical outcomes.MethodsSputum was collected from 174 stable COPD subjects longitudinally over 12 months. Microbial sampling using culture and qPCR was performed. Spirometry and sputum measures of airway inflammation were assessed.FindingsSputum was qPCR-positive (>106 copies/mL) in 77/152 samples (Haemophilus influenzae [n=52], Moraxella catarrhalis [n=24], Streptococcus pneumoniae [n=19], and Staphylococcus aureus [n=7]). Sputum was culture-positive in 50/174 samples, with 49 out of 50 culture-positive samples having pathogen-specific qPCR bacterial loads >106 copies/mL. Samples that had qPCR copy numbers >106/mL, whether culture-positive or not, had increased sputum neutrophil counts. H. influenzae qPCR copy numbers correlated with sputum neutrophil counts (r=0.37, P<0.001), were repeatable within subjects, and were >106/mL three or more times in 19 patients, eight of whom were repeatedly sputum culture-positive. Persistence, whether defined by culture, qPCR, or both, was associated with a higher sputum neutrophil count, lower forced expiratory volume in 1 second (FEV1), and worsened quality of life.InterpretationqPCR identifies a significant number of patients with potentially bacteria-associated neutrophilic airway inflammation and disease that are not identified by traditional culture-based methods.

Short-chain fatty acids affect cystic fibrosis airway inflammation and bacterial growth.

The hypoxic environment of cystic fibrosis airways allows the persistence of facultative anaerobic bacteria, which can produce short-chain fatty acids (SCFAs) through fermentation. However, the relevance of SCFAs in cystic fibrosis lung disease is unknown. We show that SCFAs are present in sputum samples from cystic fibrosis patients in millimolar concentrations (mean±sem 1.99±0.36 mM).SCFAs positively correlated with sputum neutrophil count and higher SCFAs were predictive for impaired nitric oxide production. We studied the effects of the SCFAs acetate, propionate and butyrate on airway inflammatory responses using epithelial cell lines and primary cell cultures. SCFAs in concentrations present in cystic fibrosis airways (0.5-2.5 mM) affected the release of granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor and interleukin (IL)-6. SCFAs also resulted in higher IL-8 release from stimulated cystic fibrosis transmembrane conductance regulator (CFTR) F508del-mutant compared to wild-type CFTR-corrected bronchial epithelial cells. At 25 mM propionate reduced IL-8 release in control but not primary cystic fibrosis epithelial cells. Low (0.5-2.5 mM) SCFA concentrations increased, while high (25-50 mM) concentrations decreased inducible nitric oxide synthase expression. In addition, SCFAs affected the growth of Pseudomonas aeruginosa in a concentration- and pH-dependent manner.Thus, our data suggest that SCFAs contribute to cystic fibrosis-specific alterations of responses to airway infection and inflammation.

Characterization of the inflammatory response to inhaled lipopolysaccharide in mild to moderate chronic obstructive pulmonary disease.

Lipopolysaccharide (LPS) inhalation causes increased airway and systemic inflammation. We investigated LPS inhalation in patients with chronic obstructive pulmonary disease (COPD) as a model of bacterial exacerbations. We studied safety, changes in sputum and systemic biomarkers. We have also investigated interleukin (IL)-17 concentrations in this model. Twelve COPD patients inhaled 5 μg LPS. Safety was monitored over 24 h. Sputum was induced at baseline, 6 and 24 h for cells and IL-8, IL-17, neutrophil elastase, monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1β (MIP-1β) in supernatants. Serum was collected at baseline, 4, 8 and 24 h for IL-6, C-reactive protein (CRP) and Clara cell protein (CC-16) concentrations. Peripheral blood mononuclear cells (PBMCs) were isolated at baseline and 4 h for systemic IL-17 analysis. LPS 5 μg was well tolerated. The greatest FEV1 change was 11.7% (mean) at 1 h (95% CI 5.1-18.2%). There was a large range in maximal fall (2.5-37.7%). Total sputum cell count and neutrophil count significantly increased 6 and 24 h post-LPS. There was no change in sputum supernatant mediators. IL-6, CRP and CC-16 increased post-inhalation, with different temporal patterns. CD4+ and CD8+ cell associated IL-17 significantly increased at 4 h. Inhaled LPS in COPD patients safely causes increased airway and systemic inflammation. This may be a model for studying COPD exacerbations.

The safety and tolerability of oral AZD5069, a selective CXCR2 antagonist, in patients with moderate-to-severe COPD

BackgroundChronic obstructive pulmonary disease (COPD) is characterized by neutrophil-dominated airway mucosal inflammation and elevated neutrophil counts in sputum and lung tissue. CXC chemokine receptor 2 (CXCR2) is predominantly expressed on neutrophils and mediates the migration of neutrophils to inflammatory sites. AZD5069 is a small molecule CXCR2 antagonist with the potential to inhibit neutrophil migration into the airways in patients with COPD. MethodsThis 4-week, randomized, double-blind, placebo-controlled, parallel-group, multi-center, Phase IIa study evaluated the safety and tolerability of AZD5069 in patients with moderate-to-severe COPD (ClinicalTrials.gov identifier: NCT01233232). The pharmacokinetics and effect of AZD5069 on blood neutrophil counts were also assessed. Patients completed daily diary cards and attended weekly clinic visits for safety assessments. Results87 patients (mean FEV1 56% pred; mean age 64 years; 69% male) were randomized to receive placebo (n = 29), AZD5069 50 mg bid (n = 30) or AZD5069 80 mg bid (n = 28) for 4 weeks. AZD5069 was well tolerated with adverse events (AEs) reported in 9 (31%), 10 (33%) and 6 (21%) patients in the placebo, AZD5069 50 mg and AZD5069 80 mg groups, respectively. AEs were generally mild or moderate in severity. The incidence of infections, the most commonly reported AE, was similar across the three groups (17%, 17% and 11% of patients in the placebo, AZD5069 50 and 80 mg groups, respectively). Blood neutrophil counts decreased on average from baseline by 14–40% and 13–36% in the AZD5069 50 mg and 80 mg groups, respectively, and 4 patients discontinued from the study due to decreased neutrophil count, 3 in the AZD5069 50 mg group and 1 in the 80 mg group. The systemic exposure (AUC and Cmax) of AZD5069 increased less than in proportion to the dose and there was a large overlap in the individual exposures between the two dose levels. ConclusionsAZD5069 was well tolerated overall in those patients who completed study treatment, with no increase in infection rates in either dosage group compared with placebo. Further studies with AZD5069 appear to be warranted.

Airway inflammation and ammonia exposure among female Palestinian hairdressers: a cross-sectional study

ObjectivesLittle is known about the working conditions and airway inflammation in hairdressers in Palestine. We aimed to investigate if hairdressers in Palestine have a higher level of airway inflammation as...

Clinical characteristics and airway inflammation profile of COPD persistent sputum producers

COPD patients with chronic bronchitis include a subgroup with persistent sputum production on most or every day. We hypothesized that COPD patients with persistent sputum production have a different profile of airway inflammation, and more severe clinical characteristics. To compare the airway inflammation profile and clinical characteristics of COPD persistent and non-persistent sputum producers. COPD persistent sputum producers (n = 26) and non-persistent sputum producers (n = 26) underwent sputum induction and pulmonary function tests. Exacerbation history was recorded; the St. George's Respiratory Questionnaire, Modified Medical Research Council Dyspnoea scale and COPD Assessment Tool were completed. 33 COPD patients provided sputum for bacteriology. Persistent sputum producers had lower post-bronchodilator FEV1% predicted (p = 0.01), diffusion capacity (p = 0.04), 6 min walk test distance (p = 0.05), and higher closing volume (p = 0.01), BODE index (p = 0.01), rate of bacterial colonization (p = 0.004) and exacerbations (p = 0.03) compared to non-persistent sputum producers. The mean SGRQ and CAT scores were higher in persistent sputum producers (p = 0.01 and 0.03 respectively). Sputum neutrophil and eosinophil total cell counts were higher in persistent sputum producers (p = 0.02 and 0.05 respectively). Sputum levels of eotaxin (p = 0.02), MCP-1 (p = 0.02), TNF-α (p = 0.03) and IL-6 (p = 0.05) were higher in persistent sputum producers. COPD persistent sputum producers have more severe clinical characteristics and increased concentrations of some inflammatory mediators in the airways.

Increased of exhaled breath condensate neutrophil chemotaxis in acute exacerbation of COPD

BackgroundNeutrophils have been involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). Underlying mechanisms of neutrophil accumulation in the airways of stable and exacerbated COPD patients are poorly understood. The aim of this study was to assess exhaled breath condensate (EBC) neutrophil chemotactic activity, the level of two chemoattractants for neutrophils (GRO-α and LTB4) during the course of an acute exacerbation of COPD (AECOPD).Methods50 ex smoking COPD patients (33 with acute exacerbation and 17 in stable disease) and 20 matched ex smoking healthy controls were compared. EBC was collected by using a commercially available condenser (EcoScreen®). EBC neutrophil chemotactic activity (NCA) was assessed by using Boyden microchambers. Chemotactic index (CI) was used to evaluate cell migration. LTB4 and GROα levels were measured by a specific enzyme immunoassay in EBC.ResultsStable COPD and outpatients with AECOPD, but not hospitalized with AECOPD, had raised EBC NCA compared to healthy subjects (p < 0.05 and p < 0.01 respectively). In outpatients with AECOPD EBC NCA significantly decreased 6 weeks after the exacerbation. Overall EBC NCA was weakly correlated with sputum neutrophil counts (r = 0.26, p < 0.05).EBC LTB4 levels were increased in all groups of COPD compared to healthy subjects while GRO-α was only raised in patients with AECOPD. Furthermore, EBC LTB4 and GRO-α significantly decreased after recovery of the acute exacerbation. Increasing concentrations (0.1 to 10 μg/mL) of anti- human GRO-α monoclonal antibody had no effect on EBC neutrophil chemotactic activity of 10 exacerbated COPD patients.ConclusionsEBC NCA rose during acute exacerbation of COPD in ambulatory patients and decreased at recovery. While LTB4 seems to play a role both in stable and in exacerbated phase of the disease, the role of GRO-α as a chemotactic factor during AECOPD is not clearly established and needs further investigation.

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.

Increased levels of soluble interleukin-6 receptor and CCL3 in COPD sputum.

BackgroundCOPD patients have increased numbers of macrophages and neutrophils in the lungs. Interleukin-6 (IL-6) trans-signaling via its soluble receptor sIL-6R, governs the influx of innate immune cells to inflammatory foci through regulation of the chemokine CCL3. We hypothesized that there would be enhanced levels of IL-6, sIL-6R and CCL3 in COPD sputum.Methods59 COPD patients, 15 HNS and 15 S underwent sputum induction and processing with phosphate buffered saline to obtain supernatants for IL-6, sIL-6R and CCL3 analysis. Cytoslides were produced for differential cell counting and immunocytochemistry (COPD; n = 3) to determine cell type surface expression of the CCL3 receptors CCR5 and CCR1.ResultsCOPD patients expressed higher levels (p < 0.05) of sIL-6R and CCL3 compared to controls (sIL-6R medians pg/ml: COPD 166.4 vs S 101.1 vs HNS 96.4; CCL3 medians pg/ml: COPD 117.9 vs S 0 vs HNS 2.7). COPD sIL-6R levels were significantly correlated with sputum neutrophil (r = 0.5, p < 0.0001) and macrophage (r = 0.3, p = 0.01) counts. Immunocytochemical analysis revealed that CCR5 and CCR1 were exclusively expressed on airway macrophages.ConclusionEnhanced airway generation of sIL-6R may promote IL-6 trans-signaling in COPD. Associated upregulation of CCL3 may facilitate the recruitment of macrophages into the airways by ligation of CCR1 and CCR5.Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-014-0103-4) contains supplementary material, which is available to authorized users.

Sputum Eicosanoid Profiling in Exacerbations of Chronic Obstructive Pulmonary Disease

Background: Eicosanoids are small lipid molecules with diverse biological functions in the airways. Objectives: The aim of this study was to investigate changes in leukotriene B₄ (LTB₄), 8-isoprostane, prostaglandin E₂ (PGE₂) and cysteinyl-leukotriene (cys-LT) levels in the sputum of patients with chronic obstructive pulmonary disease (COPD) at the onset of a severe exacerbation and during the course of recovery. Methods: Thirty-seven ex-smoker COPD patients suffering an episode of acute exacerbation were enrolled. Samples were taken (i) on hospital admission and (ii) after regular treatment. Twenty-five stable ex-smoker COPD patients served as controls. Eicosanoids were determined by enzyme immunoassay. Results: Sputum PGE₂ [39.8 (13.3-103.3) vs. 5.05 (2.3-12.1) pg/ml, p < 0.001], 8-isoprostane [89.5 (36.9-184.7) vs. 29.7 (13.8-68.8) pg/ml, p < 0.01] and LTB₄ [587.7 (252.9-774.8) vs. 276.1 (105.4-594.7) pg/ml, p < 0.05] levels were increased in patients with exacerbation compared to stable subjects. After treatment only PGE₂ levels decreased significantly [at discharge: 19.6 (4.6-52.5) pg/ml, p < 0.01], the levels of other eicosanoids remained elevated (p = NS). Sputum cys-LT levels were similar in stable patients and in those with exacerbation and treatment did not influence cys-LTs either. There was a significant correlation between PGE₂ and sputum neutrophil and lymphocyte cell counts in patients with exacerbation. Conclusions: Our results suggest that 8-isoprostane, LTB₄ and PGE₂ but not cys-LTs may be involved in exacerbation-associated inflammatory processes in the airways of patients with COPD. Validation of PGE₂ for use as a biomarker of recovery from an exacerbation requires further studies.

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 …

Effects of a FLAP inhibitor, GSK2190915, in asthmatics with high sputum neutrophils

Patients with refractory asthma frequently have neutrophilic airway inflammation and respond poorly to inhaled corticosteroids. This study evaluated the effects of an oral 5-lipoxygenase-activating protein (FLAP) inhibitor, GSK2190915, in patients with asthma and elevated sputum neutrophils.Patients received 14 (range 13–16) days treatment with GSK2190915 100 mg and placebo with a minimum 14 day washout in a double-blind, cross-over, randomised design (N = 14). Sputum induction was performed twice pre-dose in each treatment period to confirm sputum neutrophilia, and twice at the end of each treatment period. The primary endpoint was the percentage and absolute sputum neutrophil count, averaged for end-of-treatment visits.GSK2190915 did not significantly reduce mean percentage sputum neutrophils (GSK2190915-placebo difference [95% CI]: −0.9 [−12.0, 10.3]), or mean sputum neutrophil counts (GSK2190915/placebo ratio [95% CI]: 1.06 [0.43, 2.61]). GSK2190915 resulted in a marked suppression (>90%) of sputum LTB4 and urine LTE4, but did not alter clinical endpoints. There were no safety issues.Despite suppressing the target mediator LTB4, FLAP inhibitor GSK2190915 had no short-term effect on sputum cell counts or clinical endpoints in patients with asthma and sputum neutrophilia.

Sputum neutrophil counts are associated with more severe asthma phenotypes using cluster analysis

Clinical cluster analysis from the Severe Asthma Research Program (SARP) identified 5 asthma subphenotypes that represent the severity spectrum of early-onset allergic asthma, late-onset severe asthma, and severe asthma with chronic obstructive pulmonary disease characteristics. Analysis of induced sputum from a subset of SARP subjects showed 4 sputum inflammatory cellular patterns. Subjects with concurrent increases in eosinophil (≥2%) and neutrophil (≥40%) percentages had characteristics of very severe asthma. To better understand interactions between inflammation and clinical subphenotypes, we integrated inflammatory cellular measures and clinical variables in a new cluster analysis. Participants in SARP who underwent sputum induction at 3 clinical sites were included in this analysis (n = 423). Fifteen variables, including clinical characteristics and blood and sputum inflammatory cell assessments, were selected using factor analysis for unsupervised cluster analysis. Four phenotypic clusters were identified. Cluster A (n = 132) and B (n = 127) subjects had mild-to-moderate early-onset allergic asthma with paucigranulocytic or eosinophilic sputum inflammatory cell patterns. In contrast, these inflammatory patterns were present in only 7% of cluster C (n = 117) and D (n = 47) subjects who had moderate-to-severe asthma with frequent health care use despite treatment with high doses of inhaled or oral corticosteroids and, in cluster D, reduced lung function. The majority of these subjects (>83%) had sputum neutrophilia either alone or with concurrent sputum eosinophilia. Baseline lung function and sputum neutrophil percentages were the most important variables determining cluster assignment. This multivariate approach identified 4 asthma subphenotypes representing the severity spectrum from mild-to-moderate allergic asthma with minimal or eosinophil-predominant sputum inflammation to moderate-to-severe asthma with neutrophil-predominant or mixed granulocytic inflammation.

Anti-PcrV antibody in cystic fibrosis: A novel approach targeting Pseudomonas aeruginosa airway infection

Pseudomonas aeruginosa (Pa) airway infection is associated with increased morbidity and mortality in cystic fibrosis (CF). The type III secretion system is one of the factors responsible for the increased virulence and pro-inflammatory effects of Pa. KB001 is a PEGylated, recombinant, anti-Pseudomonas-PcrV antibody Fab' fragment that blocks the function of Pa TTSS. We studied the safety, pharmacokinetic (PK), and pharmacodynamic properties of KB001 in CF subjects with chronic Pa infection. Twenty-seven eligible CF subjects (≥12 years of age, FEV1 ≥40% of predicted, and sputum Pa density >10(5) CFU/g) received a single intravenous dose of KB001 (3 mg/kg or 10 mg/kg) or placebo. Safety, PK, Pa density, clinical outcomes, and inflammatory markers were assessed. KB001 had an acceptable safety profile and a mean serum half-life of 11.9 days. All subjects had Pa TTSS expression in sputum. There were no significant differences between KB001 and placebo for changes in Pa density, symptoms, or spirometry after a single dose. However, compared to baseline, at Day 28 there was a trend towards a dose-dependent reduction in sputum myeloperoxidase, IL-1, and IL-8, and there were significant overall differences in change in sputum neutrophil elastase and neutrophil counts favoring the KB001 10 mg/kg group versus placebo (-0.61 log(10) and -0.63 log(10) , respectively; P < 0.05). These results support targeting Pa TTSS with KB001 as a nonantibiotic strategy to reduce airway inflammation and damage in CF patients with chronic Pa infection. Repeat-dosing studies are necessary to evaluate the durability of the anti-inflammatory effects and how that may translate into clinical benefit. (NCT00638365).

Chronic cough and sputum production are associated with worse clinical outcomes in stable asthma

Chronic cough and sputum production (chronic mucus hypersecretion) is a poorly described clinical feature of asthma. Our objective was to identify clinical, immunological and computed tomography (CT) measures of airway wall dimensions associated with these symptoms in smokers and never smokers with asthma. Cross-sectional data was analysed from 120 smokers and never smokers with asthma. Participants with and without a history of chronic mucus hypersecretion were compared for clinical outcomes, sputum differential cell counts and CT measures of airway dimensions (wall thickness, luminal area and percent wall area). Chronic mucus hypersecretion occurred in a higher proportion of smokers with asthma (56%) than never smokers with asthma (20%), (p<0.001) and the proportion of patients with these symptoms increased with asthma severity (p=0.003). Smokers with asthma and chronic mucus hypersecretion had worse current clinical control than smokers without those symptoms [ACQ score 2.3 versus 1.6, p=0.002]. A greater proportion of never smokers with chronic mucus hypersecretion required short courses of oral corticosteroids in the last year (58% versus 19%, p=0.011). Sputum neutrophil and eosinophil counts were similar in asthma patients with or without chronic mucus hypersecretion. Of those with severe asthma and chronic mucus hypersecretion, a CT measure of airway lumen area was reduced in smokers compared to never smokers (11.4mm(2) versus 18.4mm(2); p=0.017). Chronic mucus hypersecretion occurs frequently in adults with stable asthma, particularly in smokers with severe disease and is associated with worse current clinical control in smokers and more exacerbations in never smokers.

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...

Relationship between airway neutrophilia and ageing in asthmatics and non‐asthmatics

Increased sputum neutrophilia has been observed in asthma, but also during normal ageing in asthmatics and non-asthmatics. It remains unclear what constitutes 'normal' neutrophil levels in different age groups. We assessed the relationship between age and airway neutrophils of 194 asthmatics and 243 non-asthmatics (age range: 6-80 years). Regression analyses were used to assess this relationship adjusted for confounders including asthma status, atopy, gender, smoking and current use of inhaled corticosteroids (ICS). Age-corrected reference values for different age groups were determined using the 95th percentile of non-asthmatic participants. Age was positively associated with sputum neutrophils in both asthmatic and non-asthmatic adults (0.46% neutrophil increase/year (95% confidence interval (CI) 0.18, 0.73) and 0.44%/year (0.25, 0.64, respectively), but no association was found in the <20-year age category. Individuals with high sputum neutrophil counts (>95th percentile of non-asthmatic counts for any given age group) were significantly more likely to be asthmatic (odds ratio = 2.5; 95% CI: 1.3, 5.0), with the greatest effect observed in the older age group. Other factors that independently associated with increased sputum neutrophil levels included atopy in non-asthmatic adults, male gender and current use of ICS in asthmatic adults. Age-specific reference values for neutrophil percentage were under 20 years-76%, 20-40 years-62%, 40-60 years-63% and over 60 years-67%. Airway neutrophilia is related to age in adults, with a neutrophilic asthma phenotype present in older adults. The use of appropriate age-specific reference values is recommended for future studies aimed at elucidating the role of neutrophils in asthma.

When are biomarkers useful in the management of airway diseases?

Biomarkers are characteristics that are objectively measured and evaluated as indicators of biological or pathogenic processes, or responses to therapeutic interventions, and may provide information on the prognosis or progression of the disease and response to treatment. They are likely to be helpful in the management of airway diseases because of the heterogeneity of their pathobiology. Most biomarkers have been developed and evaluated to assess the airway inflammation (or bronchitis) associated with airway diseases. These include quantitative cell counts in sputum, fraction of nitric oxide in exhaled breath, and various metabolites in exhaled breath. This review provides a brief description of these biomarkers with a particular emphasis on how eosinophil and neutrophil counts in sputum could be used to manage airway diseases such as asthma, chronic obstructive pulmonary disease, and chronic cough.

Distribution of sputum cellular phenotype in a large asthma cohort: predicting factors for eosinophilic vs neutrophilic inflammation

BackgroundPhenotyping asthma according to airway inflammation allows identification of responders to targeted therapy. Induced sputum is technically demanding. We aimed to identify predictors of sputum inflammatory phenotypes according to easily available clinical characteristics.MethodsThis retrospective study was conducted in 508 asthmatics with successful sputum induction recruited from the University Asthma Clinic of Liege. Receiver-operating characteristic (ROC) curve and multiple logistic regression analysis were used to assess the relationship between sputum eosinophil or neutrophil count and a set of covariates. Equations predicting sputum eosinophils and neutrophils were then validated in an independent group of asthmatics.ResultsEosinophilic (≥3%) and neutrophilic (≥76%) airway inflammation were observed in 46% and 18% of patients respectively. Predictors of sputum eosinophilia ≥3% were high blood eosinophils, FENO and IgE level and low FEV1/FVC. The derived equation was validated with a Cohen’s kappa coefficient of 0.59 (p < 0.0001). ROC curves showed a cut-off value of 220/mm3 (AUC = 0.79, p < 0.0001) or 3% (AUC = 0.81, p < 0.0001) for blood eosinophils to identify sputum eosinophilia ≥3%. Independent predictors of sputum neutrophilia were advanced age and high FRC but not blood neutrophil count.ConclusionEosinophilic and paucigranulocytic asthma are the dominant inflammatory phenotypes. Blood eosinophils provide a practical alternative to predict sputum eosinophilia but sputum neutrophil count is poorly related to blood neutrophils.