A role for Leukotriene B4 in the induction of airway hyper-responsiveness was explored through the use of transgenic mice deficient in the BLT1 receptor for LTB4 . Ovalbumin challenge of sensitized wild-type mice resulted in the usual features of experimental asthma, including goblet cell hyperplasia, hyper-responsiveness to inhaled methacholine and elevated BAL fluid concentrations of the Th2 cytokine IL-13. In contrast, BLT1 –/– mice (i.e. genetically modified mice lacking the gene coding for the BLT1 receptor) exhibited significantly lower responses. BLT1 –/– mice also exhibited lower numbers of IL-13-positive T lymphocytes of both the helper (CD4 T Cells) and cytotoxic/suppressor (CD8 + ) types. (more…)

The immunologic mechanisms of sublingual immunotherapy are less established. In Cochrane analysis, the authors concluded that there was an increase in IgG4 but no stable effect on IgE levels in adults. In addition, the induction of allergen-specific IgA has been reported. There are conflicting data concerning lympho-proliferative responses. So far the evidence on changes in Th1/Th2/Treg activity induced by sublingual immunotherapy need to be confirmed. The effects on T-cell reactivity and cytokine secretion show strong variation in a number of studies. (more…)

With the help of well-trained and experienced pulmonary function technicians, children as young as 4 to 5 years of age should be capable of performing spirometry. Spirometry measures forced vital capacity (FVC), forced expiratory volume in 1 second (FEV 1 ), the ratio of FEV 1 /FVC, as well as other measures of airflow including the forced expiratory flow between 25% and 75% of FVC (FEF 25–75 ). The FEV 1 is the most commonly used and reproducible measure of pulmonary function, whereas the FEF 25–75 demonstrates much more intrapatient variability. (more…)

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A general pattern of factors influencing development of asthma seems to be emerging, including family allergy history/ asthma genetics, smoking, diet, obesity, and inactivity, all of which seem to influence the development of asthma and disease outcomes (Table bellow).

Many clinical or area studies have reported substantially higher rates of asthma prevalence, hospitalization, and mortality among racial and ethnic minorities. However, asthma is also most common among low socioeconomic groups, regardless of race. While black children have higher rates of asthma than white children, most studies have found that black race is not a significant correlate of asthma after controlling for location of residence and socioeconomic status (SES). The basis for the effects of poverty and urban residence on asthma prevalence is not known. One potential asthma factor is allergen exposure and allergen sensitization are common in urban environments. Black children in inner city Atlanta are exposed to high levels of dust mites and cockroach allergen, and a high proportion of the children with asthma were sensitized to these allergens. Litonjua and colleagues also concluded that a large proportion of racial/ethnic differences in asthma prevalence can be explained by factors related to income, area of residence, and level of education.

Asthma Factors that Influence Disease Development and Severity

Income is a determinant of access to health care, and frequently, the quantity and quality of health care available. Persons who have low income, regardless of race or ethnicity, are more likely to be uninsured, to encounter delays or be denied care, to rely on hospital clinics in emergency departments for health services, and to receive substandard care. The usual socioeconomic indicators, education and personal or household income, serve only as surrogates for more complicated correlates of individuals within populations and multiple asthma factors that can impact both on prevalence of asthma and adverse outcomes from the disease.

Studies from Germany comparing the populations of East and West Germany have shown the prevalence of hay fever and asthma as significantly higher in West German children, suggesting that asthma environmental factors explain the difference in prevalence in these ethnically similar populations. Early exposure to infections (as with being in a day-care environment early in life) or exposure to endotoxin (as with growing up on a farm with close exposure to the farm animals) are associated with a decreased prevalence of asthma. In contrast, growing up in an urban environment or generally with an increased standard of living are associated with an increased prevalence of asthma. Such correlates are also present for atopic disorders other than asthma. In fact, Strachan, who noted that prevalence of hay fever was inversely related to family size, was the first to recognize the importance of early exposures on atopic disease. In the USA, asthma is more prevalent in African-Americans and Puerto Ricans. These findings are not explained by the observations on the role of social class in European studies. Given the ethnic differences between African-Americans and whites, these studies may represent gene-by-environment interaction producing varied phenotypic outcomes.

The intracellular forkhead winged transcription factor Foxp3 (forkhead box P3) appears to be specifically expressed by naturally occurring Treg cells, particularly in mice, although in humans there is evidence of upregulation of Foxp3 in all T cells on activation. Foxp3 is required for the development and function of naturally occurring regulatory t cells (treg) and expression is sufficient to convert non-regulatory CD4+CD25T cells into cells with regulatory activity. Conversion of peripheral CD4+CD25 naive T cells to Foxp3+CD4+CD25 foxp3+ Treg cells can be induced by TGF-ß. In a murine asthma model, these TGF-ß-induced Treg prevented house-dust mite-induced allergic pathogenesis or infection pathogenesis in lungs. A single independent report has suggested that IL-4 and IL-13 also induce Foxp3+CD25+ Treg from CD4+CD25precursors. (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…)

Anti-IgE therapy could be particularly beneficial for patients with concomitant asthma and rhinitis as it targets a common factor in the two diseases. Omalizumab is significantly more efficacious than placebo in preventing asthma exacerbations and in improving disease-related quality of life scores when added to standard asthma and rhinitis therapies. (more…)

Roflumilast is an oral, once-daily inhibitor of phosphodiesterase type 4 (PDE4) that prevents the breakdown of cyclic adenosine monophosphate (cAMP) levels, leading to inhibition of pro-inflammatory signalling. This study investigated the effects of repeated doses of 250 or 500 µg of roflumilast on airway asthma responses to allergen. (more…)

Allergic rhinitis is a very common problem associated with poor quality of life, reductions in social and work activities and poor interpersonal relationships. The main goal of the management of allergic rhinitis is to improve the quality of life. Immunotherapy is a specific therapy for allergic rhinitis and several reports have documented the safety and efficacy of this treatment . Safety has been a key issue in immunotherapy and various modalities are being investigated to make allergy immunotherapy more tolerable and safe to administer. (more…)

Allergen avoidance has been recommended in the management of allergic asthma children. Very few studies have assessed the effect of pet removal on pet allergic asthma. The authors examined the effect of pet removal from homes on pulmonary function testing, bronchial
hyper-responsiveness and medication use. This was a prospective, controlled but non-randomized and open study. Subjects included 20 symptomatic patients with newly diagnosed pet allergic asthma who were keeping domestic animals, including hamsters, cats, dogs and ferrets, and were sensitized to these animals. (more…)