Role of the immune cells, mediators and cytokines in pathogenesis of asthma: a review article

Asthma is a chronic inflammatory disorder of the airways, associated with airway re-modeling and hyperresponsiveness. It is expressed that asthma influences about 300 million people around the world, which is estimated to increase to about 400 million by 2025. The prevalence rate is 15 to 20 percent in children and 5 to 10 percent in adults, while its trend is still increasing. Inflammation plays an important role in the patho-physiology of asthma, which involves an interaction of different types of the immune cells and mediators. It leads to a number of pathophysiology changes, including bron-chial inflammation, airway obstruction, and clinical episodes such as cough, wheeze and shortness of breath. Asthma is now greatly being introduced as a heterogeneous disorder and it is pointed out to the role of T cells, including Th1, Th2, Th17, and regu-latory T cells. Other immune cells, especially neutrophils, macrophages and dendritic cells, as well structural cells such as epithelial and airway smooth muscle cells also produce disease-associated cytokines in asthma. Increased levels of these immune cells and cytokines have been recognized in clinical samples and mouse models of asthma. Different cytokines, including pro-inflammatory cytokines [such as TNF[alpha], IL-1, and IL-6], T helper 2 cytokines [such as IL-4, IL-5, IL-9, IL-13], and growth factors [such as GM-CSF, PDGF] play a role in the pathogenesis of asthma. Indeed chemokines [such as MPC-1, RANTES, MIP-1] and the chemokine receptors [such as CCR3, CCR4, CCL11, CCL24, and CCL26] play an important role in the recruitment of circu-lating inflammatory cells into the airways in asthmatic patients and also is related with increased T helper 2 cytokines after inhaled allergens. Among new approaches, treat-ment of asthma with anti-cytokine drugs such as antibodies blocking IL-4, IL-5, IL-9 could reduce recruitment inflammatory cells into the airways and remodeling. The final perspective of asthma treatments would be to alter from the symptomatic treatments to disease modifying

Infectious and non-infectious complications among undiagnosed patients with common variable immunodeficiency

Common variable immunodeficiency [CVID] is a heterogeneous group of disorders, characterized by hypogammaglobulinemia, defective specific antibody responses to pathogens and increased susceptibility to recurrent bacterial infections. Delay in diagnosis and inadequate treatment can lead to irreversible complications and mortality. In order to determine infectious complications among undiagnosed CVID patients, 47 patients diagnosed in the Children's Medical Center Hospital during a period of 25 years [1984-2009] were enrolled in this study. Patients were divided into two groups including Group 1 [Gl] with long diagnostic delay of more than 6 years [24 patients] and Group 2 [G2] with early diagnosis [23 patients]. The clinical manifestations were recorded in a period prior to diagnosis in Gl and duration follow up in G2. The number of infections, non infectious complications, hospitalizations, and mortality rate was compared between the two groups. The patients in Gl group had 500 episodes of infections before diagnosis in 256 patient-years [0.08 per patient per year] and 203 times of hospitalization [0.03 per patient per year], which were significantly higher than in G2 patients, who had 75 episodes of infections [0.015 per patient per year] and 88 hospital admissions [0.018 per patient per year] during 207 patient follow-up years. Frequency of enteropathies and liver diseases in Gl were also significantly higher than in G2. Lack of awareness about nature of disease, especially among rural and suburban physicians, single organ involvement as a site of clinical presenting, and predomination of non infectious presentation in Gl were the major factors of delayed diagnosis. Diagnostic delay is a major concern in CVID patients, which could result in irreversible complications and mortality, while early diagnosis and proper initial treatment leads to better outcomes and quality of life