The prevalence of aspirin-sensitive asthma is uncertain although it may exist in up to 20% of all asthmatics patients. The characteristic features include profound bronchoconstriction asthma following aspirin ingestion, rhinosinusitis, nasal polyps, and abdominal cramps. Aspirin and nonsteroidal antiinflammatory drugs selectively inhibit COX-1, which in turn shunts arachidonic acid down the 5-lipoxygenase activating protein pathway, causing overproduction of cysteinyl leukotrienes. As a consequence, elevated levels of cysteinyl leukotrienes can be found in bronchial asthma and nasal aspirates, and in urine following aspirin challenge. (more…)

Leukotrienes can be found in the airway and urine following both spontaneous exacerbations of asthma and acute exposure to bronchoconstrictor stimuli in the laboratory. This in turn indicates that they may have a role in the pathogenesis of acute episodes of bronchoconstriction. Although antileukotrienes are not currently advocated in the management of acute asthma, there are data to suggest that they might be of some potential benefit. Prior treatment with montelukast asthma has been shown in several studies to significantly shorten the time taken to recover (in terms of FEV 1 ) following exposure to a bronchoconstrictor stimulus. (more…)

Treg cells or regulatory T cells constitute a large population of cellular infiltrate in atopic/allergic inflammation and a dysregulated immune response appears to be an important pathogenetic factor. Cardinal events during allergic inflammation can be classified as activation, organ-selective homing, survival and reactivation, and effector functions of immune system cells. T cells are activated by aeroallergens, food antigens, autoantigens, and bacterial exotoxins superantigens in allergic inflammation. They are under the influence of the skin, lung, or nose-related chemokine network and show organ-selective homing. (more…)

A variety of proinflammatory cells, mediators, and cytokines orchestrate the development of airway hyperresponsiveness, which results in the episodic airflow obstruction characteristic of asthma. As a consequence, modulation of the underlying disease process with antii-nflammatory agents is firmly established as being the cornerstone of successful management. Inhaled corticosteroids are the most potent antiinflammatory agents available and satisfactorily suppress underlying airway inflammation in most individuals. (more…)

An especially elaborate and important type of innate antimicrobial enzymes defense is provided by a group of serum proteins that together make up the complement cascade pathway. This group comprises more than two dozen different liver-and macrophage-derived proteins, called complement factors or components, most of which normally circulate in the form of proenzymes that have latent protease activity. As a rule, each of the proteases becomes active when proteolytically cleaved and will then catalyze cleavage and activation of a different complement component. (more…)

Routes by which infectious organisms gain entry into the body include the skin, respiratory tract, gastro-intestinal (GI) tract and GU tract. There are fundamentally two ways in which infectious agents cross the physical and chemical barriers: either they are able to penetrate the intact barriers at one or more anatomical sites, or the physical barriers are damaged and breached, allowing entry of the organism.

Bellow are some possibles pathogens entry into human body:

Penetration of intact skin or mucosa

• Skin. Few organisms are able to penetrate intact skin. However, some parasites (e.g. hookworm) or their larvae (e.g. schistosoma) can do this. Other agents, such as wart viruses, set up infection in the skin and do not enter further into the body.

• Mucosa. Mucosa, being softer and damper than skin, are much more frequent sites of entry and all intact mucosa can be penetrated by some organisms. Examples are shown in table bellow. Pathogens can cross epithelia by passing through epithelial cells, as in the case of the meningococcus (a bacteria causing meningitis), or by passing between the epithelial cells, seen with Haemophilus influenzae.

Mucosal Sites of Entry for Pathogens

Penetration of damaged skin or mucosa

There are many ways in which skin or mucosa can be damaged, allowing entry of infectious organisms that could not cross intact skin or mucosa. Damage to skin is a particularly important route of infection and can occur in a number of ways:

• Burns. Burns, especially severe ones, pose a major risk for infection, particularly with Staphylococcus, Streptococcus, Pseudomonas and Clostridium tetanus.

• Cuts and wounds. These can allow entry of similar organisms to those seen after burns.

• Insect bites. Numerous infections pathogenesis are transmitted via insect bites. These include malaria, typhus and plague.

• Animal bites. Animal bites can provide direct transmission of infection, such as in rabies. Because they cause significant damage to the skin, bites can allow the entry of the same environmental pathogens as burns, cuts and wounds (see above).

• Human behaviour. Various aspects of uniquely human behaviour can result in the skin being penetrated. Sharing of syringes by intravenous (IV) drug users exposes them to risk of hepatitis and human immunodeficiency virus (HIV). A number of viral infections (hepatitis, HIV) have been transmitted by blood transfusion and blood products (e.g. factor VIII for haemophiliacs) before appropriate screening procedures were developed. Transplantation has also resulted in transmission of infection before the introduction of appropriate donor screening.

Damage to mucosa may not increase the likelihood of infection to the same extent as damage to the skin. However, physical or chemical damage may allow entry of some organisms (e.g. smoking increases the risk of respiratory bacterial infections or respiratory allergies). Furthermore, infection of the mucosa with a virus may cause damage and facilitate the entry of bacterial pathogens spread.

Normally present at very low levels in plasma, antibodies of the immunoglobulin E (IgE) isotype were first discovered in 1967, decades after the description of IgA, IgG, and IM. IgE antibodies are produced primarily by plasma cells in mucosal-associated lymphoid tissue and their levels are uniformly elevated in patients suffering from atopic conditions like allergic rhinitis, asthma and atopic dermatitis. Production of allergen-specific IgE in atopic individuals is driven both by a genetic predisposition to the synthesis of this isotype as well as by environmental factors, including chronic allergen exposure. (more…)

Allergic rhinitis and asthma are common comorbidities. Like asthma, the presence of a genetic component in allergic rhinitis has been well established. To identify genetic linkage regions unique to allergic rhinitis, as well as those shared by allergic rhinitis and asthma, a genome screen study was conducted. A total of 295 families in the French Epidemiological Study on the Genetics and Environment of Asthma (EGEA) containing 1317 subjects were genotyped for 396 microsatellite markers. The families included had two siblings with DNA available and at least one asthmatic subject. Three definitions of allergic rhinitis were used, two binary and one categorical. To investigate linkages specific to allergic rhinitis (without asthma), linkage analyses were also conducted in 185 families with at most one asthmatic sib. (more…)

The Tcell Ig domain and mucin domain (TIM) proteins, the genes for which are located on chromosome 5q, have been suggested to be involved in allergic disease. This study examined allergies genetic association of sequence variants of the TIM1 and TIM3 genes in an African-American population. Case–control and family based association analyses were performed for three SNPs each in the TIM1 and TIM3 genes, and an insertion/deletion polymorphism in Tcell Ig domain and mucin domain 1. (more…)

Tumour Necrosis Factor is a pro-inflammatory cytokine implicated in the pathogenesis of asthmatic airway inflammation, hyper-reactivity and remodelling. The primary aim of the trial was to assess whether TNF antagonism, using a soluble Tumour Necrosis Factor receptor (TNFR:Fc etanercept, Enbrel ® ), can attenuate eosinophilic airway inflammation in patients with mild to moderate allergic asthma. (more…)