Inducible nitric oxide synthase expression is increased in the alveolar compartment of asthmatic patients

Tufvesson, Ellen; Andersson, Cecilia; Weidner, Julie; Erjefält, Jonas; Bjermer, Leif

doi:10.1111/all.13052

Cited by 19 publications

(8 citation statements)

References 35 publications

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“…Therefore, our results suggest that mepolizumab may promptly reduce distal inflammation, alleviating small airway obstruction and contributing to clinical and functional improvement. Since the small airways, associated with in loco overexpression of inducible NO synthase [34], are directly involved in the pathogenesis of severe asthma, our data are of interest.…”

Section: Discussionmentioning

confidence: 99%

A Comprehensive Evaluation of Mepolizumab Effectiveness in a Real-Life Setting

Cameli

Bergantini

d’Alessandro

et al. 2020

Int Arch Allergy Immunol

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Introduction: Interleukin-5 (IL-5) is the principal cytokine regulating eosinophil growth, differentiation, activation, and expression. It is a specific target of mepolizumab, an anti-IL-5 monoclonal antibody used in the treatment of severe eosinophilic asthma. This new drug can improve symptoms, reduce asthma exacerbations and steroid use. Few data are available on its efficacy for nasal symptoms. Objective: To describe the all-round clinical impact of mepolizumab in a real-life setting, evaluating the efficacy and safety of the drug in severe eosinophilic asthma patients. Population and Methods: We retrospectively collected the clinical and functional data on 27 patients (16 males) affected with severe eosinophilic asthma, diagnosed at the Siena Regional Referral Centre and monitored for 6 months. Clinical, immunological, and functional data at baseline and follow-up were entered in a database together with comorbidities, number of exacerbations, steroid treatment, multiple-flow exhaled nitric oxide, and validated questionnaires. Results: A significant reduction in asthma exacerbations was observed in all patients after 6 months of the biological therapy (p = 0.0009), and 4/6 patients discontinued chronic oral steroids. A significant improvement in ACT, FEV1, SNOT22, and alveolar nitric oxide was observed after 1 month of mepolizumab (p = 0.003, p = 0.007, p = 0.047, and p = 0.019, respectively) and maintained after 6 months of treatment. After 6 months, FeNO 50 was reduced as well (p = 0.030). Mepolizumab was very well tolerated, and no major side effects were observed. Conclusions: Our study suggests that mepolizumab is effective in improving control of asthma, lung function parameters, exhaled biomarkers, and nasal symptoms in patients with severe eosinophilic asthma.

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Section: Discussionmentioning

confidence: 99%

A Comprehensive Evaluation of Mepolizumab Effectiveness in a Real-Life Setting

Cameli

Bergantini

d’Alessandro

et al. 2020

Int Arch Allergy Immunol

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“…Recently, the iNOS levels of both bronchial and alveolar tissues have been increased in uncontrolled asthma. However, although they showed that iNOS levels in BAL macrophages are not reflected by CANO(2CM), they did not investigate CANO(TMAD) or CANO(non‐linear) . It is difficult to clarify whether AMs or AECs are the main cell sources of iNOS.…”

Section: Discussionmentioning

confidence: 99%

Comparison of inducible nitric oxide synthase mRNA expression in different airway portions and association with nitric oxide parameters from patients with asthma

Chibana

Horigane

Uchida

et al. 2019

Clin Experimental Allergy

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BackgroundFractional exhaled nitric oxide concentration (FeNO) is widely used to support diagnosis and monitoring of bronchial asthma (BA). Tsoukias and George proposed a two‐compartment model (2CM) for assessing the alveolar concentration of NO, referred to as CANO(2CM), while Condorelli et al proposed a model based on the trumpet shape of the airway tree and axial diffusion (TMAD), referred to as CANO(TMAD). In addition, Högman et al proposed non‐linear model, referred to as CANO(non‐linear).ObjectiveWe examined associations between the expression of inducible nitric oxide synthase (iNOS) mRNA in airway cells (ACs) by bronchoscopy and NO‐parameters calculated by the three methods and identified which of them accurately reflected expression of iNOS mRNA from different airway portions.MethodsWe retrospectively analysed data of 18 patients with stable, mild‐moderate asthma, including 10 steroid‐naïve BA (snBA) patients. Samples were obtained from airway brushings and bronchoalveolar lavage (BAL). Expressions of iNOS protein in tissue samples were evaluated by immunostaining. The iNOS mRNA in ACs was measured by qPCR. NO‐parameters calculated by the three methods above and evaluated whether they were associated with iNOS mRNA in ACs derived from proximal (2nd carina), distal (10‐15th) airways and alveolar regions.ResultsImmunostaining revealed expression of iNOS proteins mainly in epithelial cells in the airways, while it was mainly expressed in macrophages in the alveolar region in the snBA group. The iNOS mRNA expression was increased in both proximal and distal ACs in the snBA group compared with steroid‐treated BA group (stBA). CANO(2CM) negatively associated with FEV 1 (%predicted) and also associated with iNOS mRNA in distal ACs significantly. However, CANO(TMAD) and CANO(non‐linear) showed no correlation with lung function nor iNOS mRNA expression in any portions of ACs.ConclusionsThese results suggested that CANO(2CM) reflected distal airway inflammation in steroid‐naïve asthma.

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“…From another brush, the brush cells were placed on microscope slides using a Cytospin TM cytocentrifuge, fixed with 4% paraformaldehyde (PFA) and stored in phosphate buffered saline (PBS) until later staining (Tufvesson et al 2017).…”

Section: Brush Samples and Bronchoalveolar Lavagementioning

confidence: 99%

Club cell protein (CC16) in plasma, bronchial brushes, BAL and urine following an inhaled allergen challenge in allergic asthmatics

et al. 2017

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Inducible nitric oxide synthase expression is increased in the alveolar compartment of asthmatic patients

Abstract: The levels of both bronchial and alveolar iNOS are increased in uncontrolled as compared to controlled asthma. However, levels of iNOS in BAL macrophages were not reflected by alveolar NO. Both central and distal iNOS levels may reflect responsiveness to steroid treatment.

Cited by 19 publications

References 35 publications

A Comprehensive Evaluation of Mepolizumab Effectiveness in a Real-Life Setting

A Comprehensive Evaluation of Mepolizumab Effectiveness in a Real-Life Setting

Comparison of inducible nitric oxide synthase mRNA expression in different airway portions and association with nitric oxide parameters from patients with asthma

Club cell protein (CC16) in plasma, bronchial brushes, BAL and urine following an inhaled allergen challenge in allergic asthmatics

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