Relation of oxidant-antioxidant imbalance with disease progression in patients with asthma.

Ann Thorac Med. 2012 Oct;7(4):226-32

Authors: Ahmad A, Shameem M, Husain Q

Abstract
CONTEXT: Asthma is a chronic airway disorder which is associated to the inflammatory cells. Inflammatory and immune cells generate more reactive oxygen species in patients suffering from asthma which leads to tissue injury.
AIMS: To investigate the role of oxidant-antioxidant imbalance in disease progression of asthmatic patients.
SETTINGS AND DESIGN: In this study, 130 asthmatic patients and 70 healthy controls were documented.
METHODS: For this malondialdehyde level, total protein carbonyls, sulfhydryls, activity of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), total blood glutathione, and total antioxidant capacity (FRAP) were measured.
STATISTICAL ANALYSIS USED: Analysis of the data was done using unpaired student t test and one-way ANOVA analysis. P < 0.05 was considered significant.
RESULTS: The present work showed that the systemic levels of MDA (4.19 ± 0.10 nmol/ml, P < 0.001) and protein carbonyls (1.13 ± 0.02 nmol/mg, P < 0.001) were found to be remarkably higher in asthmatic patients while protein sulfhydryls (0.55 ± 0.01 mmol/l, P < 0.05) decreased as compared to controls (2.84 ± 0.12 nmol/ml, 0.79 ± 0.02 nmol/mg and 0.60 ± 0.02 mmol/l, respectively). We also observed decrease in activities of SOD (2047 ± 50.34 U/g Hb, P < 0.05), catalase (4374 ± 67.98 U/g Hb, P < 0.01), and GPx (40.97 ± 1.05 U/g Hb, P < 0.01) in erythrocytes compared to control (2217 ± 60.11 U/g Hb, 4746 ± 89.94 U/g Hb, and 48.37 ± 2.47 U/g Hb, respectively). FRAP level (750.90 ± 21.22 μmol/l, P < 0.05) in plasma was decreased, whereas total blood glutathione increased (0.94 ± 0.02 mmol/l, P < 0.05) as seen in control (840.40 ± 28.39 μmol/l and 0.84 ± 0.04 mmol/l).
CONCLUSIONS: This work supports and describes the hypothesis that an imbalance between oxidant-antioxidant is associated to the oxidative stress which plays a significant role in severity of the disease.

PMID: 23189100 [PubMed - in process]

Abrupt withdrawal of inhaled corticosteroids does not result in spirometric deterioration in chronic obstructive pulmonary disease: Effect of phenotyping?

Ann Thorac Med. 2012 Oct;7(4):238-42

Authors: Al-Kassimi FA, Alhamad EH, Al-Hajjaj MS, Abba AA, Raddaoui E, Shaikh SA

Abstract
BACKGROUND AND OBJECTIVE: Some studies show a decline of FEV(1) only one month after withdrawal of inhaled corticosteroids (ICS), while others show no decline. We speculate that the presence of an asthma phenotype in the Chronic Obstructive Pulmonary Disease (COPD) population, and that its exclusion may result in no spirometric deterioration.
METHODS: We performed a prospective clinical observation study on 32 patients who fulfilled the Global Initiative for Chronic Obstructive lung disease definition of COPD (Grade II-IV). They were divided into two phenotypic groups. 1. Irreversible asthma (A and B) (n = 13): A. Asthma: Bronchial biopsy shows diffuse thickening of basement membrane (≥ 6.6 μm). B. Airflow limitation (AFL) likely to be asthma: KCO > 80% predicted if the patient refused biopsy. 2. COPD (A and B) (n = 19): A. COPD: hypercapneic respiratory failure with raised bicarbonate, panlobular emphysema with multiple bullas, or bronchial biopsy showing squamous metaplasia and epithelial/subepithelial inflammation without thickening of the basement membrane. B. AFL likely to be COPD: KCO < 80% predicted.
RESULTS: The asthma phenotype was significantly younger, had a strong association with hypertrophy of nasal turbinates, and registered a significant improvement of FEV(1) (350 ml) vs a decline of - 26.5 ml in the COPD phenotype following therapy with budesonide/formoterol for one year. Withdrawal of budesonide for 4 weeks in the COPD phenotype resulted in FEV(1) + 1.33% (SD ± 5.71) and FVC + 1.24% (SD ± 5.32); a change of <12% in all patients.
CONCLUSIONS: We recorded no spirometric deterioration after exclusion of the asthma phenotype from a COPD group.

PMID: 23189102 [PubMed - in process]

Related Articles

Structural and genetic basis for development of broadly neutralizing influenza antibodies.

Nature. 2012 Sep 27;489(7417):566-70

Authors: Lingwood D, McTamney PM, Yassine HM, Whittle JR, Guo X, Boyington JC, Wei CJ, Nabel GJ

Abstract
Influenza viruses take a yearly toll on human life despite efforts to contain them with seasonal vaccines. These viruses evade human immunity through the evolution of variants that resist neutralization. The identification of antibodies that recognize invariant structures on the influenza haemagglutinin (HA) protein have invigorated efforts to develop universal influenza vaccines. Specifically, antibodies to the highly conserved stem region of HA neutralize diverse viral subtypes. These antibodies largely derive from a specific antibody gene, heavy-chain variable region IGHV1-69, after limited affinity maturation from their germline ancestors, but how HA stimulates naive B cells to mature and induce protective immunity is unknown. To address this question, we analysed the structural and genetic basis for their engagement and maturation into broadly neutralizing antibodies. Here we show that the germline-encoded precursors of these antibodies act as functional B-cell antigen receptors (BCRs) that initiate subsequent affinity maturation. Neither the germline precursor of a prototypic antibody, CR6261 (ref. 3), nor those of two other natural human IGHV1-69 antibodies, bound HA as soluble immunoglobulin-G (IgG). However, all three IGHV1-69 precursors engaged HA when the antibody was expressed as cell surface IgM. HA triggered BCR-associated tyrosine kinase signalling by germline transmembrane IgM. Recognition and virus neutralization was dependent solely on the heavy chain, and affinity maturation of CR6261 required only seven amino acids in the complementarity-determining region (CDR) H1 and framework region 3 (FR3) to restore full activity. These findings provide insight into the initial events that lead to the generation of broadly neutralizing antibodies to influenza, informing the rational design of vaccines to elicit such antibodies and providing a model relevant to other infectious diseases, including human immunodeficiency virus/AIDS. The data further suggest that selected immunoglobulin genes recognize specific protein structural 'patterns' that provide a substrate for further affinity maturation.

PMID: 22932267 [PubMed - indexed for MEDLINE]

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Comparison of the bronchodilating effects of albuterol delivered by valved vs. non-valved spacers in pediatric asthma.

Pediatr Allergy Immunol. 2012 Nov;23(7):629-35

Authors: Rodriguez-Martinez CE, Sossa-Briceño MP, Castro-Rodriguez JA

Abstract
INTRODUCTION: Inhaled therapy using a metered-dose inhaler (MDI) with attached valved holding chamber has been increasingly recognized as the optimal method for delivering bronchodilators for asthma treatment. However, mainly due to the high cost of these valved holding chambers in many developing countries, the use of non-valved spacers is frequent, despite the scarce evidence that supports their efficacy. The aim of this study was to compare the bronchodilator response to albuterol administered by MDI with and without a valved spacer.
METHODS: In a randomized, two-period, two-sequence crossover clinical trial, we analyzed 31 stable asthmatic children (6-18 yrs of age) on two consecutive days, who were randomly assigned to receive 100 μg of albuterol MDI through either a locally produced valved spacer or a non-valved spacer. The next day, a crossover treatment was employed through the use of the other spacer. Spirometry was recorded before and after each albuterol administration.
RESULTS: As we were not able to identify any sequence or carryover effect, we tested for treatment effects in both periods. No significant differences in the absolute change in FEV(1) (0.20 ± 0.17 vs. 0.18 ± 0.16, p = 0.63), FVC (0.07 ± 0.13 vs. 0.07 ± 0.16, p = 0.88), or MMEF (0.49 ± 0.31 vs. 0.43 ± 0.39, p = 0.53) after bronchodilator administration were found between the use of valved and non-valved spacers.
CONCLUSIONS: In stable asthmatic children, albuterol administered through MDI using a non-valved spacer produces a bronchodilator response similar to that of a spacer with a valve that requires an inhalatory opening pressure (with flows between 2 and 32 l/min) that even toddlers with bronchial obstruction can easily generate.

PMID: 23005919 [PubMed - in process]