Berry, M. et al. Pathological features and inhaled corticosteroid response of eosinophilic and non-eosinophilic asthma. Thorax 62, 1043-1049

Institute for Lung Health, Glenfield Hospital, Leicester LE3 9QP, UK.
Thorax (Impact Factor: 8.29). 01/2008; 62(12):1043-9. DOI: 10.1136/thx.2006.073429
Source: PubMed


Non-eosinophilic asthma is a potentially important clinicopathological phenotype since there is evidence that it responds poorly to inhaled corticosteroid therapy. However, little is known about the underlying airway immunopathology and there are no data from placebo-controlled studies examining the effect of inhaled corticosteroids.
Airway immunopathology was investigated using induced sputum, bronchial biopsies, bronchial wash and bronchoalveolar lavage in 12 patients with symptomatic eosinophilic asthma, 11 patients with non-eosinophilic asthma and 10 healthy controls. The patients with non-eosinophilic asthma and 6 different patients with eosinophilic asthma entered a randomised, double-blind, placebo-controlled crossover study in which the effects of inhaled mometasone 400 microg once daily for 8 weeks on airway responsiveness and asthma quality of life were investigated.
Patients with non-eosinophilic asthma had absence of eosinophils in the mucosa (median 4.4 cells/mm(2) vs 23 cells/mm(2) in eosinophilic asthma and 0 cells/mm(2) in normal controls; p = 0.03) and normal subepithelial layer thickness (5.8 microm vs 10.3 microm in eosinophilic asthma and 5.1 microm in controls, p = 0.002). Non-eosinophilic and eosinophilic asthma groups had increased mast cell numbers in the airway smooth muscle compared with normal controls (9 vs 8 vs 0 cells/mm(2), p = 0.016). Compared with placebo, 8 weeks of treatment with inhaled mometasone led to less improvement in methacholine PC(20) (0.5 vs 5.5 doubling concentrations, 95% CI of difference 1.1 to 9.1; p = 0.018) and asthma quality of life (0.2 vs 1.0 points, 95% CI of difference 0.27 to 1.43; p = 0.008).
Non-eosinophilic asthma represents a pathologically distinct disease phenotype which is characterised by the absence of airway eosinophilia, normal subepithelial layer thickness and a poor short-term response to treatment with inhaled corticosteroids.

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    • "Most often primary cares' physicians do not require a chest X-ray (CXR) mainly because of the tremendous cost expenses and lack of X-ray equipment setups as well as lack of specialist staff. On the other hand the dynamic of blood cell count (CBC) has been used as a reliable clinical predictor for the severity of a variety of inflammatory conditions [35] [4], yet its implementations to classify asthma severity have been ignored. Clearly, chronic inflammatory process of the airways must be associated with a significant rise in white cell count (WBC), yet its implementations to classify the severity of asthma had been poorly understood. "
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    ABSTRACT: The purpose of the present study was to rate the level of spread of asthma-induced bronchial morphological changes on chest X-ray (CXR), using the modified Shwachman–Kulczycki (S–K) rating scale as predicted by the dynamic of blood cell count (CBC). A sample of 40 asthma patients’ records was classified into 4 groups based on their clinical presentations and frequency of their visits to the hospital; Group-1 ⩽2 visits per week with reversible symptoms, Group-2 ⩾2 visits per week with irreversible symptoms, Group-3: ⩾3–4 visits per week with irreversible symptoms; Group-4: patients with severe shortness of breath in whom SaO2 was threatening, hence were admitted as inpatients. Patients’ CXR were scored based on the modified Shwachman–Kulczycki (S–K) scale rating. Blood analysis showed that RBC and their indices (HCT, HGB, MCH, RDW) were highest in group-2. White blood cells and their derivatives (NEU, EOS and LYM) were highest in group 4. CXR for group-2 showed bilateral increased bronchovascular markings but normal both lung fields and ruled out for costo-phrenic angles type of fever. Chest X-ray for group-3 showed hyperinflation, perihilar marking associated with bronchial thickening and unfolding aorta. In patients in group-4 development of broncho-pneumonic infiltration type of SOB and some evidence of bronchial edema with significant (p < 0.05) elevation in WBC were observed. The regression of S–K score on the dynamic of some CBC parameters was significant (p < 0.05). The best subsets that describe the model were:
    Full-text · Article · Feb 2015
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    • "While the addition of a LABA is generally recommended, in a subset of patients an increase in ICS dose may be more appropriate. For instance, patients whose asthma is characterised by elevated sputum eosinophil levels have been found to display substantially greater response to ICS than patients with non-eosinophilic asthma [25]. There is evidence to suggest that increasing ICS dose in such patients may be effective in reducing asthma exacerbations [26]. "
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    ABSTRACT: Background Inhaled corticosteroids are a mainstay of therapy for persistent asthma, but suboptimal adherence with twice-daily use is widespread. Fluticasone furoate (FF) is a new inhaled corticosteroid (ICS) suitable for once-daily dosing in asthma. This study was performed to descriptively assess the efficacy and safety of two doses of FF, with no planned formal statistical hypothesis testing. Methods This was a 24-week double-blind, multicentre, parallel-group study (NCT01431950). Patients aged ≥ 12 years with moderate-severe persistent asthma and uncontrolled on mid-high dose ICS were stratified by baseline FEV1 and randomised (1:1) to treatment with FF 100 μg or 200 μg once daily in the evening. The primary endpoint was change from baseline trough FEV1 after 24 weeks; secondary and other endpoints included peak expiratory flow (PEF) and rescue-free and symptom-free 24-hour periods over Weeks 1–24, and Asthma Control Test™ (ACT) score at Week 24. A pre-specified subgroup analysis of patients by randomisation strata was performed for the primary and selected secondary and other endpoints. Safety assessments included adverse events, laboratory and vital sign measurements, and change from baseline in 24-hour urinary cortisol at Week 24. Results With FF 100 μg and 200 μg, least squares mean trough FEV1 improved from baseline by 208 mL and 284 mL, respectively, at Week 24; treatment difference: 77 mL (95% CI: –39, 192). Similar improvements from baseline in rescue- and symptom-free periods, and morning and evening PEF were observed in both groups. Patients were 42% more likely to be well-controlled (ACT score ≥ 20) with FF 200 μg than with FF 100 μg. Slightly more patients receiving FF 200 μg vs. FF 100 μg reported adverse events (63% vs. 59%) and events deemed treatment related (5% vs. <1%). Seven serious adverse events (FF 200 μg 4; FF 100 μg 3) were reported, none of which were deemed treatment related. No clinically relevant effects of either dose on 24-hour urinary cortisol were observed. Conclusion Improvements from baseline in trough FEV1 were observed after 24 weeks of treatment with both doses of FF, with a numerically greater improvement in FEV1 observed in patients receiving FF 200 μg. Secondary endpoint findings were similar between groups. No safety concerns were identified during the study.
    Full-text · Article · Jul 2014 · BMC Pulmonary Medicine
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    • "A neutrophilic pattern of inflammation is typically noticed in the bronchoalveolar lavage fluid of patients with chronic inflammatory airway disease, including CF, chronic bronchitis and bronchoectasis [23,24]. Non-eosinophilic asthma represents an alternative asthma phenotype in which patients exhibit asthma symptoms and heightened airway responsiveness in the absence of significant eosinophilia [25]. "
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    ABSTRACT: Lambda-cyhalothrin (LTC) is a synthetic pyrethroid insecticide for agricultural and public health applications. This study was to determine the pathological alterations of LTC in lungs, which has not previously been studied, and the ameliorating effects of plant extracts (ginseng and garlic) on the development of asthma in albino rats. Four groups (gps) of albino rats, (n = 20, average body weight = 200 gm with an age of 4 months), were formed. Gp 1 was kept as control. Gp 2 was injected intraperitoneally (i.p.) with LTC at a dose of 1/6 LD50 that is 9.34 mg/kg body weight (w.t.) daily for 21 days (d). Gp 3 & 4 were injected (i.p.) with ginseng at the dose of 200 mg/kg b.wt and garlic (Allium sativum L.) at the dose of 100 mg/kg b.wt., respectively, one hour before being given LTC at a dose of 1/6 LD50 (9.34 mg/kg b.wt.) daily. Each groups were divided into two sacrificed, at 15 and 21 d p.i. Blood and lung samples were collected for hematological and histopathological examinations. Hematological findings showed that the animals in gps 2 and 3, which were treated for 21 days, showed a significant difference in RBC counts (P > .001), Hb (P > .007), PCV% (P > .004), (P > .008) in comparison with the control group. Signs of cough and nasal discharge were seen in gp 2, which became mild in gp 4. Grossly, the lungs showed congestion and consolidation in gp 2. Histopathologically, macroabscesses and interstitial alveolitis were seen in gp 2, which led to obstruction in the lumen of the bronchioles at 21 d p.i. Meanwhile, thickening in the interalveolar septa with mononuclear cells was seen in gps. 3 and 4 at 21d p.i. The study shows 3 gps of rats injected with LHC alone or combined with garlic and ginseng extract, each group were divided into two sacrificed (15 and 21 d p.i.). Lambda cyhalothrin causes bronchial obstruction in the lungs of the rats (15 and 21 d p.i), which decreased into mild to moderate interstitial inflammation in the rats given garlic and ginseng, respectively.
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