Airway and Serum Biochemical Correlates of Refractory Neutrophilic Asthma

Juan Carlos Ivancevich Thursday, 09 February 2017 11:46

Abstract

Background

Despite the progress in diagnosis and management of asthma, many patients have poorly controlled or refractory asthma. The mechanism of this refractory asthma is not well understood.

Objective

Explore the relationship between neutrophils and other biomarkers of refractory asthma.

Method

Sixty subjects with refractory asthma (RA), 30 with non-refractory asthma (NRA) and 20 healthy subjects were enrolled. We performed a comprehensive characterization of these study subjects, which included laboratory and pulmonary function studies, chest CT, and bronchoscopy with bronchoalveolar lavage. We analyzed BAL and serum for a total of 244 biomolecules by multiplex assay and correlated them with the clinical and other laboratory parameters.

Results

RA was significantly different from NRA with regard to pulmonary function indices, bronchial basement membrane thickness, and BAL neutrophils and lymphocytes but not eosinophils. BAL neutrophils negatively and positively correlated with the forced vital capacity and age, respectively. Of the 244 biomolecules studied, 52 and 14 biomolecules from BAL and serum, respectively, were significantly different among the study groups. Thirteen of these 52 molecules correlated with BAL neutrophils. BAL from 40% of RA patients was positive for a pathogenic microbe. Infection-negative neutrophilic RA was associated with an increase in select biomarkers of inflammation in the serum suggesting the presence of systemic inflammation.

Conclusions

RA was associated with increased number of neutrophils and proneutrophilic biomolecules in the airways. Subclinical infection was present in 40% of RA patients, which likely contributed to neutrophilic inflammation. A subgroup of non-infected neutrophilic RA was associated with systemic inflammation.

http://www.jacionline.org/article/S0091-6749(17)30147-1/abstract

Association of stem cell factor gene expression with severity and atopic state in patients with bronchial asthma

Juan Carlos Ivancevich Saturday, 04 February 2017 16:36
 
Safaa I. Tayel, Sally M. El-Hefnway, Eman M. Abd El Gayed and Gehan A. Abdelaal

Abstract

Background

Bronchial asthma is a chronic inflammatory and remodeling disorder of the airways, in which many cells, cellular elements, and cytokines play important roles. Stem cell factor (SCF) may contribute to the inflammatory changes occurring in asthma. We aimed to show the expression of SCF gene in patients with asthma as a means of diagnosis and its association with severity and atopic state in these patients.

Methods

This study was carried out on 80 subjects, 50 asthmatic patients and 30 age and gender matched healthy control persons. They were subjected to full history taking, general and local chest examination, spirometric measurements (pre and post broncodilators) using a spirometer, serum IgE, and real time PCR for assessment of SCF mRNA expression.

Results

This study showed significant difference between the studied groups regarding pulmonary function tests (P < 0.001). Asthmatic patients had significant higher SCF expression compared to control (P < 0.001), also atopic patients vs non atopic (P = 0.03) and severe asthmatic patients vs mild ones (P < 0.001). SCF expression at cut off point (0.528) is sufficient to discriminate asthmatic patients from control while at cut off point (1.84) for discrimination of atopic patients from non-atopic patients and at cut off point (1.395) for discrimination of severe asthmatic patients from mild ones. A significant negative correlation between SCF expression and inhaled steroid while significant positive correlation with serum IgE was found.

Conclusion

Measuring SCF mRNA expression can be used as an efficient marker for evaluation of atopy and detection of severity of bronchial asthma.

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What patients really think about asthma guidelines: barriers to guideline implementation from the patients’ perspective

Juan Carlos Ivancevich Sunday, 29 January 2017 14:47

Abstract

Background

Treatment of asthma does not always comply with asthma guidelines (AG). This may be rooted in direct or indirect resistance on the doctors’ and/or patients’ side or be caused by the healthcare system. To assess whether patients’ concepts and attitudes are really an implementation barrier for AG, we analysed the patients’ perspective of a “good asthma therapy” and contrasted their wishes with current recommendations.

Methods

Using a qualitative exploratory design, topic centred focus group (FG) discussions were performed until theoretical saturation was reached. Inclusion criteria were an asthma diagnosis and age above 18. FG sessions were recorded audio-visually and analysed via a mapping technique and content analysis performed according to Mayring (supported by MAXQDA®). Participants’ speech times and the proportion of time devoted to different themes were calculated using the Videograph System® and related to the content analysis.

Results

Thirteen men and 24 women aged between 20 and 77 from rural and urban areas attended five FG. Some patients had been recently diagnosed with asthma, others years previously or in childhood. The following topics were addressed: (a) concern about or rejection of therapy components, particularly corticosteroids, which sometimes resulted in autonomous uncommunicated medication changes, (b) lack of time or money for optimal treatment, (c) insufficient involvement in therapy choices and (d) a desire for greater empowerment, (e) suboptimal communication between healthcare professionals and (f) difficulties with recommendations conflicting with daily life. Primarily, (g) participants wanted more time with doctors to discuss difficulties and (h) all aspects of living with an impairing condition.

Conclusions

We identified some important patient driven barriers to implementing AG recommendations. In order to advance AG implementation and improve asthma treatment, the patients’ perspective needs to be considered before drafting new versions of AG. These issues should be addressed at the planning stage.

Trial registration

DRKS00000562 (German Clinical Trials Registry).

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Respiratory effect of beta-blockers in people with asthma and cardiovascular disease: population-based nested case control study

Juan Carlos Ivancevich Wednesday, 01 February 2017 13:03

Daniel R. Morales, Brian J. Lipworth, Peter T. Donnan, Cathy Jackson and Bruce Guthrie

Abstract

Background

Cardiovascular disease (CVD) is a common comorbidity in people with asthma. However, safety concerns have caused heterogeneity in clinical guideline recommendations over the use of cardioselective beta-blockers in people with asthma and CVD, partly because risk in the general population has been poorly quantified. The aim of this study was to measure the risk of asthma exacerbations with beta-blockers prescribed to a general population with asthma and CVD.

Methods

Linked data from the UK Clinical Practice Research Datalink was used to perform nested case-control studies among people with asthma and CVD matched on age, sex and calendar time. Adjusted incidence rate ratios (IRR) were calculated for the association between oral beta-blocker use and moderate asthma exacerbations (rescue oral steroids) or severe asthma exacerbations (hospitalisation or death) using conditional logistic regression.

Results

The cohort consisted of 35,502 people identified with active asthma and CVD, of which 14.1% and 1.2% were prescribed cardioselective and non-selective beta-blockers, respectively, during follow-up. Cardioselective beta-blocker use was not associated with a significantly increased risk of moderate or severe asthma exacerbations. Consistent results were obtained following sensitivity analyses and a self-controlled case series approach. In contrast, non-selective beta-blockers were associated with a significantly increased risk of moderate asthma exacerbations when initiated at low to moderate doses (IRR 5.16, 95% CI 1.83–14.54, P = 0.002), and both moderate and severe exacerbations when prescribed chronically at high dose (IRR 2.68, 95% CI 1.08–6.64, P = 0.033 and IRR 12.11, 95% CI 1.02–144.11, P = 0.048, respectively).

Conclusions

Cardioselective beta-blockers prescribed to people with asthma and CVD were not associated with a significantly increased risk of moderate or severe asthma exacerbations and potentially could be used more widely when strongly indicated.

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Subtypes of asthma based on asthma control and severity: a latent class analysis

Juan Carlos Ivancevich Friday, 27 January 2017 20:01
 

Abstract

BACKGROUND: Asthma subtyping is a complex new field of study. Usually both etiological and outcome factors of asthma have been used simultaneously for subtyping thus making the interpretation of the results difficult. Identification of subtypes of asthma based on questionnaire data only will be useful for both treatment of asthma and for research. Our objective was to identify asthma subtypes that capture both asthma control and severity based on easily accessible variables.

METHODS: We applied latent class analysis for the 1995 adult asthmatics, 692 men and 1303 women, of the Northern Finnish Asthma Study (NoFAS). The classifying variables included use of asthma medication within the last 12 months, St. George's Respiratory Questionnaire score, and asthma-related healthcare use within the last 12 months. Covariates adjusted for included COPD, allergic rhinitis/allergic eczema, BMI, age and sex. All information was based on self-administered questionnaires.

RESULTS: We identified four subtypes for women: Controlled, mild asthma (41% of participants); Partly controlled, moderate asthma (24%); Uncontrolled asthma, unknown severity (26%), and Uncontrolled, severe asthma (9%). For men we identified three subtypes: Controlled, mild asthma (31%); Poorly controlled asthma, unknown severity (53%); and Partly controlled, severe asthma (17%). For almost 96% of the subjects this subtyping was accurate. The covariates fitted in the model were based on clinical judgment and were good predictors of class membership.

CONCLUSIONS: Our results show that it is possible to form meaningful and accurate asthma subtypes based on questionnaire data, and that separate classification should be applied for men and women.

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Editor: Juan C. Ivancevich, MD

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