Sputum Eosinophils Research Articles

Involvement of Transforming Growth Factor-β-Associated Kinase 1 in Fixed Airway Obstruction in Asthmatic Patients with Longer Disease Duration Independent on Airway Eosinophilia.

Transforming growth factor-β-associated kinase 1 (TAK1) mediates non-canonical TGF-β signalling by promoting adhesive, migratory, proliferative and contractile responses of fibroblasts to TGF-β1. However, TAK1 expression status in asthmatic patients with or without fixed airway obstruction (FAO) is unknown. A total of 60 adult asthmatics with FAO were recruited and compared to 43 those without FAO (nFAO). TGF-β1 concentrations, and total TAK1 and phosphorylated TAK1 (p-TAK1) levels were determined in sputum supernatants, cytospin, and whole cell lysate by ELISA, immunocytochemistry, and Western blot analysis, respectively, in asthmatics with and without FAO. Asthmatic patients with FAO had much greater sputum TGF-β1 concentrations than those without FAO. This was independent of airway eosinophilia as there was no significant difference in TGF-β1 levels between high and low eosinophil counts within FAO and nFAO groups. In contrast, patients with FAO in the presence of sputum eosinophilia had greater expression of TAK1 and p-TAK1 than those without sputum eosinophilia (P=0.0032 and P=0.0061, respectively). The Western Blot data of total TAK1 and p-TAK1 were consistent with the immunocytochemistry, showing upregulation in all sputum cell types (neutrophils, eosinophils, macrophages, lymphocytes and airway epithelial cells). In addition, total TAK1 expression negatively correlated with pre- and post-bronchodilator FEV1/FVC ratio. TAK1 may play a key role in asthmatic patients with fixed airway obstruction, which was independent of eosinophilic airway inflammation. The interruption of TAK1 might have favourable clinical impact.

Sputum inflammatory, neural, and remodeling mediators in eosinophilic and noneosinophilic asthma

BackgroundNeural and remodeling mechanisms may play a role in asthma, particularly noneosinophilic asthma (NEA). ObjectiveTo assess sputum mediators associated with neural, remodeling, and inflammatory mechanisms in eosinophilic asthma (EA), NEA, and participants without asthma. MethodsA total of 111 participants with and 62 without asthma (14-21 years old) underwent sputum induction, exhaled nitric oxide, atopy, and spirometry tests. There were 24 mediators measured in sputum using enzyme-linked immunosorbent assay or bead array. Eosinophilic asthma (n = 52) and NEA (n = 59) were defined using a sputum eosinophil level cut-point of greater than or equal to 2.5%. ResultsElevated levels of nociceptin (median: 39.1 vs 22.4 ng/mL, P = .03), periostin (33.8 vs 9.4 ng/mL, P = .01), and ECP; (220.1 vs 83.7 ng/mL, P = .03) were found in patients with asthma compared with those without asthma. Nociceptin was elevated in EA (54.8 vs 22.4 ng/mL, P = .02) compared with participants without asthma. Eosinophilic asthma had higher levels of inflammatory mediators (ECP: 495.5 vs 100.3 ng/mL, P ≤ .01; interleukin-1β: 285.3 vs 209.3 pg/mL, P = .03; histamine: 5805.0 vs 3172.5 pg/mL, P < .01) and remodeling mediators (VEGF-A); 3.3 vs 2.5 ng/mL, P = .03; periostin: 47.7 vs 22.1 ng/mL, P = .04) than NEA. Whereas macrophages were associated with neural mediators, for example, neurokinin A (r = 0.27, P = .01) and nociceptin (r = 0.30, P = .02), granulocytes were associated with inflammatory and remodeling mediators (eg, ECP and VEGF-A correlated with neutrophils (r = 0.53 and r = 0.33, respectively, P < .01) and eosinophils (r = 0.53 and r = 0.29 respectively, P ≤ .01). ConclusionElevated levels of nociceptin and inflammatory and remodeling markers were found in EA, but no evidence for neural and remodeling pathways was found in NEA. Neural and remodeling mechanisms seem to coexist with inflammation.

CCL5 is a potential bridge between type 1 and type 2 inflammation in asthma

Type 1 (T1) inflammation (marked by IFN-γ expression) is now consistently identified in subsets of asthma cohorts, but how it contributes to disease remains unclear. We sought to understand the role of CCL5 in asthmatic T1 inflammation and how it interacts with both T1 and type 2 (T2) inflammation. CCL5, CXCL9, and CXCL10 messenger RNA expression from sputum bulk RNA sequencing, as well as clinical and inflammatory data were obtained from the Severe Asthma Research Program III (SARP III). CCL5 and IFNG expression from bronchoalveolar lavage cell bulk RNA sequencing was obtained from the Immune Mechanisms in Severe Asthma (IMSA) cohort and expression related to previously identified immune cell profiles. The role of CCL5 in tissue-resident memory T-cell (TRM) reactivation was evaluated in a T1high murine severe asthma model. Sputum CCL5 expression strongly correlated with T1 chemokines (P< .001 for CXCL9 and CXCL10), consistent with a role in T1 inflammation. CCL5high participants had greater fractional exhaled nitric oxide (P= .009), blood eosinophils (P<.001), and sputum eosinophils (P= .001) in addition to sputum neutrophils (P= .001). Increased CCL5 bronchoalveolar lavage expression was unique to a previously described T1high/T2variable/lymphocytic patient group in the IMSA cohort, with IFNG trending with worsening lung obstruction only in this group (P= .083). In a murine model, high expression of the CCL5 receptor CCR5 was observed in TRMs and was consistent with a T1 signature. Arole for CCL5 in TRM activation was supported by the ability of the CCR5 inhibitor maraviroc to blunt reactivation. CCL5 appears to contribute to TRM-related T1 neutrophilic inflammation in asthma while paradoxically also correlating with T2 inflammation and with sputum eosinophilia.

Sputum-Rheology-Based Strategy for Guiding Azithromycin Prescription in COPD Patients with Frequent Exacerbations: A Randomized, Controlled Study (“COPD CARhE”)

(1) Background: We have previously shown that sputum rheology can discriminate between patients with COPD and other muco-obstructive lung diseases, and that it is correlated with mucin content and sputum eosinophilia. We now hypothesize that it could be a more-accurate guide than clinical evaluation for the prescription of azithromycin to prevent exacerbations of COPD and to reduce exposure to antibiotics; (2) Methods: "COPD CaRhe" is a multicentric, randomized, controlled trial comparing outcomes in two parallel arms (36 vs. 36 patients). Patients will be recruited in the university hospitals of Montpellier, Bordeaux, and Toulouse, in France, and they should have a diagnosis of COPD with frequent exacerbations (≥3/year). Enrollment will occur during a routine visit to a respiratory department, and follow-up visits will occur every 3 months for a period of 1 year. At each visit, a 3-month prescription of azithromycin will be provided to those patients who obtain a score of <70 on the Cough and Sputum Assessment Questionnaire (CASA-Q) or a critical stress score of σc > 39 on a rheological assessment of sputum, depending upon their randomization group. The primary outcome will be the number of exacerbations of COPD; (3) Discussion: By using sputum rheology, the COPD CaRhe study may provide clinicians with an objective biomarker to guide the prescription of azithromycin while reducing the cumulative exposure to macrolides.

Inhaled anti-TSLP antibody fragment, ecleralimab, blocks responses to allergen in mild asthma.

Thymic stromal lymphopoietin (TSLP) is a key upstream regulator driving allergic inflammatory responses. We evaluated the efficacy and safety of ecleralimab, a potent inhaled neutralising antibody fragment against human TSLP, using allergen inhalation challenge (AIC) in subjects with mild atopic asthma. This was a 12-week, randomised, double-blind, placebo-controlled, parallel-design, multicentre allergen bronchoprovocation study conducted at 10 centres across Canada and Germany. Subjects aged 18-60 years with stable mild atopic asthma were randomised (1:1) to receive 4 mg once-daily inhaled ecleralimab or placebo. Primary end-points were the allergen-induced change in forced expiratory volume in 1 s (FEV1) during the late asthmatic response (LAR) measured by area under the curve (AUC3-7h) and maximum percentage decrease (LAR%) on day 84, and the safety of ecleralimab. Allergen-induced early asthmatic response (EAR), sputum eosinophils and fractional exhaled nitric oxide (F ENO) were secondary and exploratory end-points. 28 subjects were randomised to ecleralimab (n=15) or placebo (n=13). On day 84, ecleralimab significantly attenuated LAR AUC3-7h by 64% (p=0.008), LAR% by 48% (p=0.029), and allergen-induced sputum eosinophils by 64% at 7 h (p=0.011) and by 52% at 24 h (p=0.047) post-challenge. Ecleralimab also numerically reduced EAR AUC0-2h (p=0.097) and EAR% (p=0.105). F ENO levels were significantly reduced from baseline throughout the study (p<0.05), except at 24 h post-allergen (day 43 and day 85). Overall, ecleralimab was safe and well tolerated. Ecleralimab significantly attenuated allergen-induced bronchoconstriction and airway inflammation, and was safe in subjects with mild atopic asthma.

Correlation of Total Serum Immunoglobulin Level, Sputum and Peripheral Eosinophil Count in Assessing the Clinical Severity in Bronchial Asthma

Correlation of total serum immunoglobulin E level, sputum and peripheral eosinophil count in assessing the clinical severity in bronchial asthma. Higher percentage of sputum Eosinophil count is present in moderate and severe persistent asthma. Higher percentage of absolute eosinophil count is present in moderate and severe persistent asthma.

Sputum Type 2 Markers Could Predict Remission in Severe Asthma Treated With Anti-IL-5

Biotherapies targeting IL-5 allow a tangible improvement of asthma. However, all patients do not respond the same way to these treatments. Even if high blood eosinophil counts seem to be associated with a reduction in exacerbations with treatment targeting IL-5, we lack biomarkers for the prediction of remission after these very expensive treatments. Are there biomarkers of remission after therapy targeting IL-5 in the sputum of patients with severe eosinophilic asthma? This observational study included 52 patients with severe asthma initiated with anti-IL-5 therapy and recruited from the asthma clinic of the Centre Hospitalier Universitaire of Liege, Belgium. Remission was defined as patients who combined the following at 1 year after therapy: no chronic treatment with oral corticosteroids; no exacerbation; asthma control questionnaire score< 1.5, asthma control test score > 19, or both; FEV1 of≥ 80%predicted, improvement of FEV1 of≥ 10%, or both; and a blood eosinophil count< 300 cells/μL. Eosinophil peroxidase (EPX), IgE, IL-3, IL-4, IL-5, IL-13, IL-25, IL-33, granulocyte-macrophage colony-stimulating factor, thymic stromal lymphopoietin (TSLP), and eotaxin-1 levels were measured in the sputum of these patients before anti-IL-5 treatment. Among the 52 patients, 11 were classified as being in remission. These patients were characterized by higher sputum eosinophil, macrophage, and lymphocyte counts, whereas the sputum neutrophil percentage was lower than in the nonremission group. In addition, the sputum eotaxin-1, TSLP, IL-5, EPX, and IgE protein levels were higher at baseline in the remission group compared with the nonremission group. Univariate regression analysis revealed that male vsfemale sex, sputum neutrophil percentage, eotaxin-1, IL-5, and EPX were potential predictors of remission. Sputum type 2 markers seemed to be potentially predictive of remission after anti-IL-5 therapy in a cohort of patients with severe eosinophilic asthma. These results need validation on a larger cohort.

IL-4 and IL-13, not eosinophils, drive type 2 airway inflammation, remodeling and lung function decline.

Type 2 (T2) asthma is characterized by airflow limitations and elevated levels of blood and sputum eosinophils, fractional exhaled nitric oxide, IgE, and periostin. While eosinophils are associated with exacerbations, the contribution of eosinophils to lung inflammation, remodeling and function remains largely hypothetical. To determine the effect of T2 cytokines IL-4, IL-13 and IL-5 on eosinophil biology and compare the impact of depleting just eosinophils versus inhibiting all aspects of T2 inflammation on airway inflammation. Human eosinophils or endothelial cells stimulated with IL-4, IL-13 or IL-5 were assessed for gene changes or chemokine release.Mice exposed to house dust mite extract received anti-IL-4Rα (dupilumab), anti-IL-5 or control antibodies and were assessed for changes in lung histological and inflammatory endpoints. IL-4 or IL-13 stimulation of human eosinophils and endothelial cells induced gene expression changes related to granulocyte migration; whereas, IL-5 induced changes reflecting granulocyte differentiation.In a mouse model, blocking IL-4Rα improved lung function by impacting multiple effectors of inflammation and remodeling, except peripheral eosinophil counts, thereby disconnecting blood eosinophils from airway inflammation, remodeling and function. Blocking IL-5 globally reduced eosinophil counts but did not impact inflammatory or functional measures of lung pathology. Whole lung transcriptome analysis revealed that IL-5 or IL-4Rα blockade impacted eosinophil associated genes, whereas IL-4Rα blockade also impacted genes associated with multiple cells, cytokines and chemokines, mucus production, cell:cell adhesion and vascular permeability. Eosinophils are not the sole contributor to asthma pathophysiology or lung function decline and emphasizes the need to block additional mediators to modify lung inflammation and impact lung function.

ADX-629, A Reactive Aldehyde Species (RASP) Inhibitor, Reduced Eosinophilia In Asthmatic Subjects After Bronchial Allergen Challenge (BAC)

Aeroallergens including house dust mite (HDM) and pet dander are well-known provocateurs in atopic asthma. ADX-629, a novel RASP inhibitor, acts on inflammatory cytokines implicated in asthma. In this clinical trial, airway hypersensitivity with Methacholine Challenge (MCh), post-BAC FEV1, exhaled NO (FeNO), and sputum eosinophils (EOS) were studied to evaluate ADX-629 in asthma.

Bronchiectasis in severe asthma is associated with eosinophilic airway inflammation and activation.

Bronchiectasis is a common comorbidity in severe asthma; causative pathogenic mechanisms are not fully understood but may differ from other causes of bronchiectasis. The role of eosinophilic airway inflammation, a classic feature of asthma predominantly driven by IL-5 and IL-13, in bronchiectasis is unclear, but association with disruption of the airway epithelium through eosinophil degranulation and increased mucus production is plausible. We sought to describe the prevalence of bronchiectasis in an unselected population of patients with severe asthma, and the association with the airway eosinophilic inflammation and activation. All patients with severe asthma according to European Respiratory Society/American Thoracic Society criteria (high-dose inhaled corticosteroids/oral corticosteroids), attending 4 respiratory clinics over a 1-year period, were included. All patients underwent high-resolution computed tomography and induced sputum was collected and analyzed for a cell differential count, free eosinophilic granules, and airway messenger RNA expression of T2 inflammatory pathways. Bronchiectasis was present in 31% (34 of 108) of patients with severe asthma, and half (52%) of these patients had airway eosinophilia whereas only 16% of patients without bronchiectasis had airway eosinophilia. Patients with bronchiectasis had a significantly higher sputum eosinophil count (5.3 vs 0.8; P= .001) as well as more extensive eosinophil degranulation, compared with those without bronchiectasis (13% vs 2%; P= .05), suggesting a higher degree of eosinophil activation. Pairwise analyses identified significantly higher messenger RNA expression of Charcot-Leyden crystal galectin in patients with bronchiectasis (P= .02). Bronchiectasis in severe asthma was associated with eosinophilic airway inflammation and eosinophilic degranulation as well as messenger RNA expression of Charcot-Leyden crystal galectin.

Progress to be made in asthma management

Progress to be made in asthma management

Differing effects of mepolizumab across the life course

The history of asthma treatment is full of near misses. Inhaled and oral corticosteroids would not be in the therapeutic armamentarium if not for the late, great Harry Morrow-Brown's demonstration in 1958, using his medical school microscope, that these treatments worked well, but only in those with sputum eosinophilia. This early realisation of the importance of personalised medicine was rapidly forgotten in the excitement of new and powerful steroid-based treatments. Therefore, when the humanised anti-interleukin 5 (IL-5) monoclonal mepolizumab was first tested in adult asthma, it was nearly rejected as inactive until it was trialled in the right subgroup, namely patients with eosinophilic, attack-prone asthma.

Measurement of Blood Eosinophils in Asthma and Chronic Obstructive Pulmonary Disease.

Eosinophils are important effector cells in airway inflammation, as pleiotropy and heterogeneity can be linked to various pathophysiologies in asthma and chronic obstructive pulmonary disease (COPD). Sputum eosinophils can reflect the heterogeneity of airway inflammation, and owing to their traits, blood eosinophils can be a surrogate and potential biomarker for managing both conditions. Blood eosinophils are activated via the stimulation of type 2 cytokines, such as interleukin (IL)-5, IL-4/13, granulocyte-macrophage colony-stimulating factor, IL-33, and thymic stromal lymphopoietin. There is sufficient evidence to support the relationship between the blood eosinophil count and clinical outcomes, including pulmonary function decline, exacerbations, all-cause mortality, and treatment response to inhaled corticosteroids and biologics. Thus, there is growing interest in the use of blood eosinophils for the management of these diseases. Compiling recent evidence, we herein review the significance of measuring blood eosinophils in asthma and COPD.

Omalizumab Transitions in Severe Asthma: Factors Influencing Switching Decisions and Timing for Optimal Response

Objective: The objective of this study was to assess the effectiveness of switching from omalizumab to another biologic therapy for patients with severe asthma and evaluate factors that influenced the decision to switch and determined the optimal time for a good biologic response. Subjects and Methods: A retrospective study of severe asthma patients was conducted at Al-Rashed Allergy Center, a tertiary center in Kuwait. After meeting the eligibility criteria, patients were divided into two comparative groups: those continuing with omalizumab and those who started with omalizumab but switched to another biologic. Results: One hundred sixteen patients with severe asthma were recruited, and only 33 had access to multiple biological treatments. Approximately 22.4% switched from omalizumab. Male patients with a history of ischemic heart disease, chronic rhinosinusitis, and nasal polyps were more likely to switch if they had higher levels of eosinophils in the sputum. This study showed that every 1% increase in sputum eosinophils doubled the likelihood of a switch. Patients with access to alternative biological options had a much shorter mean duration of omalizumab therapy before switching compared to those with only affordable omalizumab: 4.9 ± 1.5 years versus 8.9 ± 1.3 years (p < 0.001). The optimal time to predict the likelihood of a good response was less than 5.5 years, with an area under the curve of 0.91 and p = 0.003. This cutoff point provided a sensitivity and specificity of approximately 89% and 100%, respectively. Conclusion: An early transition from omalizumab, specifically within the first 5 years of treatment, in patients with severe asthma and higher sputum eosinophils may enhance the likelihood of a good response if other biological therapies were available.

Study on Asthma and Chronic Obstructive Pulmonary Disease Overlaps among Patients with Obstructive Airway Diseases

Background and Aim: Although asthma and chronic obstructive pulmonary disease (COPD) are clinically distinct diseases, they represent biologically diverse and overlapping clinical entities and it has been observed that they often co-occur. Some research and theorizing suggest there is a common comorbid condition termed asthmachronic obstructive pulmonary disease overlap (ACO). However, the existence of ACO is controversial.Material and Methods: This is prospective, observational and descriptive study conducted at tertiary care institute of Gujarat for the duration of 1 year. Among chronic airway diseases who were classified into three groups (COPD, asthma and ACO). Patients with COPD and ACO were diagnosed according to GOLD guidelines 2020 and patients with asthma were diagnosed according to Global Initiative for Asthma (GINA) guidelines 2020. Total 150 participants were included in the research. All patients are subjected to full history taking, clinical examination, full laboratory examinations, chest radiography, spirometry and post bronchodilator reversibility test was performed and sputum analysis, where induction of sputum by hypertonic saline or mannitol is done by a trained staff with strict airborne respiratory precautions.Results: We found that 71.42% of ACO group, 79.48% of asthma group and 25% of COPD group had a positive history of atopy. Comparison of study groups regarding sputum eosinophils revealed that 30.15 % of ACO group, 76.92% of asthma group and 31.25% of COPD group had positive sputum eosinophils.Conclusion: ACO addresses an enormous rate among patients with obstructive airway diseases. It shares a few highlights of asthma like atopy and positive sputum eosinophilia, and a few highlights of COPD like old age of shows and positive smoking history

Sputum eosinophil count to assess response to treatment in children with asthma

Sputum eosinophil count to assess response to treatment in children with asthma

Nasal Transcriptome and Epigenome Analysis Identifies the Pathogenic Features of Aspirin-Exacerbated Respiratory Disease.

Dysregulation of the arachidonic acid metabolic pathway is the most widely known pathomechanism of aspirin-exacerbated respiratory disease (AERD). This study aimed to perform integrative analysis of transcriptomic and epigenomic profiling with network analysis to determine the novel pathogenic features of AERD. Ten patients with asthma including 5 patients with AERD and another 5 patients with aspirin tolerant asthma (ATA) were enrolled. Nasal scraping was performed and nasal mucosa was used in omics profiling. Peripheral eosinophil counts, sputum eosinophil counts, fractional exhaled nitric oxide levels, and pulmonary function test results were evaluated. Differentially expressed genes (DEGs), differentially methylated probes (DMPs) and differentially correlated genes (DCGs) between patients with AERD and those with ATA were analyzed. Network analysis using ingenuity pathway analysis (IPA) was performed to determine the gene connection network and signaling pathways. In total, 1,736 DEGs, 1,401 DMPs, and 19 pairs for DCGs were identified. Among DCGs, genes related to vesicle transport (e.g., RAB3B and STX2) and sphingolipid dysregulation (e.g., SMPD3) were found to be hypo-methylated and up-regulated in AERD. Using the canonical pathway analysis of IPA with 78 asthma-related DEGs, signaling pathways of T helper cell differentiation/activation and Fcε receptor I were generated. Up-regulation of RORγt and FcER1A were noted in AERD. Gene expression levels of RAB3B, SYNE1, STX2, SMPD3 and RORγt were significantly associated with sputum eosinophil counts. Quantitative real-time polymerase chain reaction was performed and mRNA expression levels of STX2, SMPD3, RORγt, and FcER1A were significantly higher in AERD compared to ATA. Distinct pathogenic features were identified by using integrative multi-omics data analysis in patients with AERD.

Клиническое значение оксида азота выдыхаемого воздуха, назального оксида азота, эозинофилов периферической крови как маркеров воспаления дыхательных путей при бронхиальной астме и аллергическом рините

Chronic airway inflammation plays an important role in the development and progression of bronchial asthma (BA) and allergic rhinitis (AR). The lack of correlation between the severity of clinical symptoms and the activity of inflammation determines the need to develop and introduce various biomarkers into clinical practice. Allergic ВА and AR are predominantly based on eosinophilic inflammation. Sufficiently studied markers of eosinophilic inflammation of the respiratory tract are peripheral blood eosinophils, exhaled nitric oxide (FeNO), nasal nitric oxide (nNO). FeNO increases in BA and AR, decreases with the use of glucocorticoids, and can be used to monitor the course of these diseases as well as in the diagnosis of BA. nNO can also be used as a surrogate marker for eosinophilic inflammation of the upper airways, but research results are conflicting, and further research is required on the clinical significance of this marker. A significant limitation of the use of nitric oxide levels in real clinical practice is the high cost of analyzers and their components. The search for cheaper markers that can be used in practical work to assess eosinophilic inflammation of the upper and lower respiratory tract, in particular, peripheral blood eosinophils, is relevant. A large number of studies have proven the possibility of using peripheral blood eosinophils as markers of eosinophilic inflammation of the lower respiratory tract. They are comparable to induced sputum eosinophils and can be useful in assessing the severity and control of asthma as well as in prescribing biological therapy. In the available literature, it was not possible to find data on the use of peripheral blood eosinophils to assess inflammation of the upper respiratory tract. Airway inflammation markers are an important tool for clarifying the phenotype/endotype of respiratory diseases and for an individual approach to the treatment of patients with BA and AR.

Induced sputum eosinophilia and pulmonary function tests in ex-smokers with asthma controlled with an inhaled steroid and long-acting beta-agonist therapy.

This study aims to investigate the relationship between induced sputum eosinophilia and pulmonary functions in ex-smoker asthma patients controlled with an ICS/LABA therapy. Asthma patients who are known to use ICS/LABA regularly for at least three months, without an attack in the last month, quit smoking (5-20 pack-years) and have asthma under control (ACT> 20), and concurrent with induced sputum cytology who had spirometry and lung volume measurements were included in the study. Cytology results, induced sputum eosinophil and neutrophil counts, FEV1 (L), FEV1 (%), FVC (L), FVC (%), RV (L), RV (%) and RV/TLC (%) values of all patients were recorded. The relationship between sputum neutrophil and eosinophil count and pulmonary function test parameters was evaluated. Seventeen (68%) of the patients were female, eight (32%) were male, and the mean age was 49.7 ± 13.6 years. The mean sputum eosinophil percentage was 9.4 ± 16.7, and the neutrophil percentage was 71.4 ± 20.5. A positive correlation was found between induced sputum eosinophil percentage values and FEV1 (L) (r= +0.472; p= 0.01) and FVC (L) (r= +0.502; p= 0.01). No correlation was found between the FEV1/FVC%, FEV1%, FVC%, RV (L), RV%, and RV/TLC% values and the percentage of induced sputum eosinophils (p> 0.05). It was observed that controlled asthmatic patients with induced sputum eosinophilia treated with ICS/LABA and who quit smoking had high FVC (L) and FEV1 (L) levels.

Association of serum CC16 levels with eosinophilic inflammation and respiratory dysfunction in severe asthma

BackgroundThere are knowledge gaps in the potential role of Club cell 16-kDa secretory protein (CC16) in severe asthma phenotypes and type 2 inflammation, as well as the longitudinal effect of CC16 on pulmonary function tests and exacerbation risk in epidemiological studies. Objective and methodsTo assess whether serum CC16 is associated with eosinophilic inflammation in patients with severe asthma. We also examined the effect of this protein on the annual decline in forced expiratory volume in the first second (FEV1) and the risk of exacerbation using a longitudinal approach. We recruited 127 patients with severe asthma from 30 hospitals/pulmonary clinics in Hokkaido, Japan. The least square means and standard error were calculated for T-helper 2 (Th2) biomarkers and pulmonary function test across CC16 tertiles at baseline. We did the same for asthma exacerbation and annual decline in FEV1 with 3 and 5 years’ follow-up, respectively. ResultsWe found that serum CC16 was inversely associated with sputum eosinophils and blood periostin in a dose-response manner. Baseline CC16 and FEV1/forced vital capacity ratio were positively associated in adjusted models (p for trend = 0.008). Patients with the lowest tertile of serum CC16 levels at baseline had a −14.3 mL decline in FEV1 than those with the highest tertile over 5 years of follow-up (p for trend = 0.031, fully adjusted model). We did not find any association of CC16 with exacerbation risk. ConclusionPatients with severe asthma with lower circulatory CC16 had enhanced eosinophilic inflammation with rapid FEV1 decline over time.