Mohamed Zedan

Clinical Asthma Phenotypes and Therapeutic Responses

Asthma is a heterogeneous disease that means not all asthmatics respond to the same treatment. We hypothesize an approach to characterize asthma phenotypes based on symptomatology (shortness of breath (SOB), cough, and wheezy phenotypes) in correlation with airway inflammatory biomarkers and FEV1. We aimed to detect whether those clinical phenotypes have an impact on the response to asthma medications. Two hundred three asthmatic children were allocated randomly to receive either montelukast (5 mg at bed time) or fluticasone propionate (100 ug twice daily) for 8 consecutive weeks. Serum concentrations of IL-2Rs, ICAM-1, VCAM-1, total IgE, eosinophilic %, eosinophil cationic protein (ECP), and FEV1 were done before and after treatment to patients and once to controls. Children who have SOB were found to have higher levels of total sIgE, older age, and longer disease duration, and they responded to fluticasone alone. Cough group was found to have higher levels of eosinophilic % and sECP, younger age, shorter disease duration and responded to montelukast alone. Wheezy group showed mixed pattern and responded to both medications. Conclusion. Although there is variability in response to ICS and LTRAs, we did identify characteristics of patient that should guide the clinician in the choice of asthma medications.

Eosinophilic cationic protein: is it useful in assessing control of childhood asthma?

This study evaluated peripheral eosinophil and serum eosinophilic cationic protein (s-ECP) levels as markers of asthma control. A total of 38 children with asthma (16 controlled and 22 partially controlled) were compared with 16 age- and sex-matched healthy children. Total asthma cases had higher eosinophil counts and s-ECP levels than healthy children and partially controlled asthmatics had significantly higher levels of both markers than controlled asthmatics. Controlled asthma cases showed non-significant changes in both parameters versus healthy children. A negative correlation was noted between degree of asthma control and both eosinophil counts and s-ECP levels (r = -0.60 and -0.75 respectively). s-ECP as well as peripheral eosinophil count may be helpful in the assessment of asthma control.

Clinical asthma phenotyping: A trial for bridging gaps in asthma management

Asthma is a common disease affecting millions of people worldwide and exerting an enormous strain on health resources in many countries. Evidence is increasing that asthma is unlikely to be a single disease but rather a series of complex, overlapping individual diseases or phenotypes, each defined by its unique interaction between genetic and environmental factors. Asthma phenotypes were initially focused on combinations of clinical characteristics, but they are now evolving to link pathophysiological mechanism to subtypes of asthma. Better characterization of those phenotypes is expected to be most useful for allocating asthma therapies. This article reviews different published researches in terms of unbiased approaches to phenotype asthma and emphasizes how the phenotyping exercise is an important step towards proper asthma treatment. It is structured into three sections; the heterogeneity of asthma, the impact of asthma heterogeneity on asthma management and different trials for phenotyping asthma.

The emergence of systemic lupus erythematosus in hypothyroid patients: two case reports and mini review.

Systemic lupus erythematosus (SLE) is a multi-systemic autoimmune disease that involves almost all the organs in the human body and is characterized by auto antibodies formation. Autoimmune thyroid diseases (AITD) are organ-specific diseases that are associated with a production of a variety of antibodies such as antinuclear antibodies, anti-double-stranded DNA, anti-Ro antibodies, anti-cardiolipin antibodies, and others. The diagnosis of AITD in patients with SLE is well known, but the reverse is rarely reported. We present two cases of adolescent girls in whom SLE evolved one year after being diagnosed with hypothyroidism.

Montelukast as an add-on treatment in steroid dependant nephrotic syndrome, randomised-controlled trial

BackgroundThe underlying mechanisms of nephrotic syndrome (NS) are still under debate and the need for more effective and less toxic treatment is challenging. We aimed to evaluate the efficacy of montelukast, a leukotriene receptor antagonist as an add-on therapy, and to explore the leukotriene (LT) biology in steroid-dependent nephrotic syndrome (SDNS).MethodsA randomized controlled trial was conducted including 32 patients with SDNS who were randomly assigned to receive standard steroid treatment only [low-dose steroid (LDS) group] or standard steroid therapy plus montelukast (Montelukast group). Urine protein/creatinine ratio, serum albumin, creatinine, cholesterol, and plasma LTs (LTB4/C4/D4/E4) were evaluated in all patients before and after treatment.ResultsAfter treatment, both groups showed a significant decrease of LTB4 and LTC4/D4/E4. Further, the Montelukast group showed a significant decrease in serum creatinine and a significant increase in diastolic blood pressure and protein/creatinine ratio. It also showed a marked decrease in plasma LTC4/D4/E4 compared to the LDS group, although not statistically significant.ConclusionsOur findings highlight the effect of montelukast on renal function, but suggest that the clinical and laboratory efficacy of the addition of montelukast to steroids in maintenance treatment of SDNS is debatable.

Progressive stridor: could it be a congenital cystic lung disease?

Bronchogenic cyst of the mediastinum, a cause of stridor early in life, is the result of abnormal budding of the ventral segment of the primitive foregut. Bronchogenic cysts are often asymptomatic in older children and adults. However, symptomatic cases usually manifest early in life with cough, stridor or wheezing due to airway compression. We report a female infant aged 4.5 months with a normal full‐term pregnancy, who developed respiratory distress with stridor. This stridor was preceded by a history of slowly progressive noisy breathing. Physical examination revealed evidence of bilateral obstructive emphysema. Chest radiograph revealed bilateral overinflation. Fibro‐optic bronchoscopy revealed posterior mediastinal compression. Possibility of congenital cystic lung disease (CCLD) was considered, emphasizing the value of computed tomography (CT) chest, which revealed a cyst probably bronchogenic. Surgical excision was performed with evident histological confirmation of bronchogenic cyst.

Effect of tranilast in comparison with beclomethasone in chronic murine model of asthma

ABSTRACT Aim of the Study: The current investigation was taken to scrutinize the action of tranilast on the airway remodeling in chronic asthma in mice. Materials and Methods: Intraperitoneal injection of ovalbumin was applied to mice for sensitization and subsequent inhalation of 1% ovalbumin three times week for 10 weeks for challenge. Beclomethasone or tranilast were given daily for the 10 week challenge period. At the end of the study, lung weight index, total collagen content, bronchoalveolar lavage level of total and differential cell counts, interleukin-13, in addition to lung tissue nitrate/nitrite and transforming growth beta-1 were measured. Also, histological analysis was done. Results: Asthmatic mice demonstrated apparent fibrotic changes. Significant airway fibrosis was demonstrated by hyperplasia of goblet cells and thickening of airway epithelium, increased content of lung collagen, lung and bronchoalveolar lavage of transforming growth factor beta-1 and interleukin-13 mutually accompanied by reduction in nitrate/nitrite generation. Conclusions: Beclomethasone influence on airway remodeling was mediated mainly via suppression of eosinophilic recruitment into the airways and reduction of interleukin-13 cytokine levels. Whereas, tranilast effects on airway remodeling was found to be mainly mediated via its inhibitory effect on transforming growth beta-1. Both beclomethasone and tranilast influence airway remodeling by different degrees and mechanisms.

Increased myeloperoxidase activity as an indicator of neutrophil-induced inflammation and sepsis in neonates

Background: MPO is an enzyme that contains heme secreted by phagocytic cells after the respiratory burst system activation. MPO is expressed mainly by neutrophils and monocytes in small quantities and it is very important to determine further process of hydrogen peroxide. Objective: to evaluate neutrophils activation and the MPO enzyme activity in plasma as an indicator of sepsis as well as sepsis severity in neonates with sepsis with correlation to their clinical and laboratory findings. Methods: were classified into 2 groups: sepsis group: included 45 neonates with gestational ages 28-40 weeks with sepsis, 15 of them had been subjected to follow up samples, control group: included 30 neonates proved to be free of sepsis. All neonates were subjected to history taking, clinical examination and measurement of plasma MPO enzyme. Results: this study revealed that MPO activity and neutrophil cell count are increased in sepsis group compared to the non-septic neonates. The ROC curve showed that the best cut off for MPO in prediction of septic patients and mortality was found >54 mu/ml and >83 mu/ml respectively. There was positive correlation between MPO enzyme activity and the total leukocyte count and neutrophil count. By following up some of sepsis group neonates there was significant decrease in MPO activity goes along with improvement in clinical state of neonates with sepsis. MPO enzyme activity was found to be low in septic shock patients who also have pancytopenia compared to septic patients without shock. Conclusion: plasma MPO enzyme proved to be a good marker of sepsis in neonates, with a good prognostic value in severe cases. Keywords: MPO, inflammatory response, neonates, sepsis