Forms Of Asthma Research Articles

MUTATION C3435T IN MULTI-DRUG RESISTANCE GENE MDR1 AS PHARMACOGENETIC MARKER OF SEVERE COURSE OF BRONCHIAL ASTHMA

Background. Early detection and treatment of severe forms of bronchial asthma (BA) is one of serious problems in clinical practice. BA is a multifactorial disease, so its progression is a result of both environmental factors and genetic predisposition. Aim of the study. To determine frequencies of genetic variants resulted from the mutation C3435T (rs1045642) in MDR1 gene among patients with different BA severity and in healthy controls. Methods. The trial included 122 patients with different severity of BA course and 103 healthy controls. Genomic DNA was extracted from peripheral blood leucocytes by routine phenol-chloroform protocol. Allelic variants were determined by polymerase chain reaction with subsequent restriction analysis with MboI restriction endonuclease. Results. For the first time association of allelic variant 3435C of MDR1 gene with BA was revealed. Differences between MDR1 genotypes distributions persisted in case of stratification BA patients according their severity courses. Severity of BA course was found to be strongly associated with 3435C allele. Conclusion. Allele 3435C and genotype 3435CC of gene MDR1 are markers of increased risk of BA progression. In patients with BA these alleles are associated with unfavorable severe course of the disease. Genotype 3435TT of gene MDR1 is a protective marker associated with favorable and well-controlled BA course.

Obesity: Changing Asthma in the 21st Century

Obesity: Changing Asthma in the 21st Century

279 Near-Fatal Asthma Treated with Omalizumab

BackgroundNear-fatal asthma treated with Omalizumab. The near-fatal asthma is a severe form of asthma that threatens the life of patients and is associated with poorly controlled chronic asthma, accounting for limitations in the quality of life. Presents with ongoing chronic inflammation and irreversible changes in the airway. Treatment is difficult, however with the use of omalizumab can decrease the risk of mortality in these patients.ObjectiveEvaluating clinical improvement, spirometric and income to the emergency hospitalization and intensive care unit, as well as near-fatal asthma episodes in patients with uncontrolled asthma in treatment with con Omalizumab.MethodsWe evaluated 4 patients with poorly controlled asthma and near-fatal episodes of asthma who were administered doses of omalizumab and IgE established according to weight, evaluating clinical, spirometric well as income to the emergency room and hospital intensive care unit.ResultsThere was a significant clinical improvement in 4 patients after treatment with omalizumab with improved daytime symptoms by 75% and 68% nocturnal P ≤ 0.001, as well as 100% improvement in revenue and hospitalizations to floor, well as income to the ICU with P ≤ 0.001. No further episodes of near-fatal asthma. In addition to decreased use of systemic steroids 90% (P 0.003) and inhaled steroids 60% (P 0.005).ConclusionsOmalizumab is a good treatment option in patients with poorly controlled asthma with near-fatal asthma episodes.

Interleukin (IL)-4, IL-13, and IL-17A differentially affect the profibrotic and proinflammatory functions of fibrocytes from asthmatic patients.

Fibrocytes contribute to the fibrotic changes most frequently observed in forms of asthma where inflammation is driven by T helper type 2 (Th2) cells. The mechanisms that regulate the profibrotic function of asthmatic fibrocytes are largely unknown. We isolated circulating fibrocytes from patients with allergen-exacerbated asthma, who showed the presence of fibrocytes, together with elevated concentrations of interleukin (IL)-4 and IL-13 and slightly increased concentrations of the Th17 cell-derived IL-17A, in induced sputum. Fibrocytes stimulated with IL-4 and IL-13 produced high levels of collagenous and non-collagenous matrix components and low levels of proinflammatory cytokines. Conversely, fibrocytes stimulated with IL-17A proliferated and released proinflammatory factors that may promote neutrophil recruitment and airway hyperresponsiveness. IL-17A also indirectly increased α-smooth muscle actin but not collagen expression in fibrocytes. Thus, fibrocytes may proliferate and express a predominant profibrotic or proinflammatory phenotype in asthmatic airways depending on the local concentrations of Th2- and Th17-derived cytokines.

Regulat ory T-cells in periphera l blood of pat ientswith br onchial ast hma

Background. To investigate the expression of surface molecules CD4+CD25high and CD4+FoxP3+ on regulatory T-cells (Treg) in patients with different severity of bronchial asthma (BA). Methods. We included 19 patients with severe BA, 12 patients with mild BA and 17 healthy donors. The circulating percentage of CD4+CD25high and CD4+FoxP3+ T-reg in peripheral blood was estimated by the flow cytometry analysis (FACSCalibur, Becton Dickinson, USA). Results. Numbers of peripheral blood CD4+CD25high was significantly decreased in mild BA compared to healthy control. Patients with severe BA had increased levels of CD4+FoxP3+ and CD4+CD25high compared to mild BA. Conclusion. Our results demonstrate new scientific data on the phenotypic characteristics and the level of T-reg in peripheral blood at different clinical forms of asthma. This fact confirms the existence of immunoregulatory control mechanisms of allergic inflammation involving T-reg.

Th17 cells: new players in asthma pathogenesis

CD4+ T effector lymphocytes are distinguished in different subsets on the basis of their patterns of cytokine secretion. Th1 cells, thank to IFN-γ production, are responsible for cell-mediated immunity against intracellular pathogens, Th2 cells, through the production of IL-4, provide some degree of protection against helminthes, and Th17 cells, via IL-17, promote neutrophils recruitment for the clearance of bacteria and fungi. However, beyond their protective role, these T-helper subsets can also be involved in the pathogenesis of several inflammatory diseases. Asthma is an inflammatory disease characterized by different clinical phenotypes. Allergic asthma is the result of an inflammatory process driven by allergen-specific Th2 lymphocytes, whereas Th17 cells are mainly involved in those forms of asthma, where neutrophils more than eosinophils, contribute to the inflammation. The identification in allergic asthma of Th17/Th2 cells, able to produce both IL-4 and IL-17, is in keeping with the observation that different clinical phenotypes can coexist in the same patient. In conclusion, a picture in which different T-cell subpopulations are active in different phase of bronchial asthma is emerging, and the wide spectrum of clinical phenotypes is probably the expression of different cellular characters playing a role in lung inflammation.

Cough and Asthma

Cough is the most common complaint for which patients seek medical attention. Cough variant asthma (CVA) is a form of asthma, which presents solely with cough. CVA is one of the most common causes of chronic cough. More importantly, 30 to 40% of adult patients with CVA, unless adequately treated, may progress to classic asthma. CVA shares a number of pathophysiological features with classic asthma such as atopy, airway hyper-responsiveness, eosinophilic airway inflammation and various features of airway remodeling. Inhaled corticosteroids remain the most important form of treatment of CVA as they improve cough and reduce the risk of progression to classic asthma most likely through their prevention of airway remodeling and chronic airflow obstruction.

Awake Coronary Artery Bypass Grafting: Initial Experience in a Rural Cardiac Centre

Two patients with significant co-morbidities in the form of bronchial asthma and hypothyroidism underwent “awake coronary artery bypass grafting” under high thoracic epidural anaesthesia. Our experience indicates that high thoracic epidural anaesthesia is beneficial in patients with co-morbid conditions undergoing coronary artery bypass grafting. (JMS 2010;13(2):64-66)

Immunotherapy in asthma

Asthma is a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role. Chronic inflammation is associated with airway hyper-responsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness and coughing, as well as variable airflow obstruction within the lung. With time, such airflow obstruction may become permanent due to remodeling. It has been treated for more than 100 years by subcutaneous immunotherapy with allergen extracts but in recent years, other forms and types of immunotherapy have been introduced. Perhaps the most successful of these to date, is sublingual immunotherapy, which has attained significant usage in European countries but has yet to make inroads into clinical practice in North America. Other mechanisms to modify the inflammatory responses of asthma have included immunotherapy with recombinant allergens, the use of allergen peptides targeting antigen-specific T cells and the administration of Toll-like receptor agonists coupled to allergen proteins. As the inflammatory responses in asthma frequently involve IgE, a modified monoclonal antibody to IgE and interfering with its binding to the IgE receptor have gained acceptance for treating severe allergic asthma. Other monoclonal antibodies or recombinant receptor antagonists are being assessed for their ability to block other contributors to the inflammatory response. Finally, attempts have been made to generate autoantibody responses to cytokines implicated in asthma. Most of these therapies aim to modify or inhibit the so-called Th 2 immune response, which is implicated in many forms of asthma, or to inhibit cytokines involved in these responses. However, an added benefit of classical immunotherapy seems to be the ability to prevent the allergic progression to new sensitivities and new forms of allergic disease.

Wheezing and Bronchial Hyper-responsiveness in Early Childhood as Predictors of Newly Diagnosed Asthma in Early Adulthood: A Longitudinal Birth-Cohort Study

Stern DA, Morgan WJ, Halonen M, Wright AL, Martinez FD. Lancet. 2008;372(9643):1058–1064PURPOSE OF THE STUDY. To estimate the contributions of gender and early life factors to newly diagnosed and persistent asthma in young adults.STUDY POPULATION. The study evaluated 849 enrollees of the Tucson Children's Respiratory Study who had adult data at 22 years of age.METHODS. The cohort was derived from all healthy infants born in Tucson, Arizona, between 1980 and 1984. Shortly after birth, the parents completed a questionnaire on demographic data and were instructed to see a collaborating pediatrician at the first sign of lower respiratory illness. Physician-diagnosed asthma or wheezing was assessed at 2, 3, 6, 8, 11, and 16 years of age. At 6 years of age, allergy skin-prick tests were performed for all participants, and cold air bronchial challenge was performed for participants with a history of lower respiratory illness. At 22 years of age, an in-depth evaluation was performed with questionnaires on asthma symptoms, asthma medication use, and smoking history. Allergy skin-prick tests and spirometry were performed for participants still living in the Tucson area.RESULTS. Subjects with adult data at 22 years of age were more likely to have nonsmoking, nonminority parents with higher levels of education than were those without adult data. Of the 849 participants, 255 (30%) had asthma diagnosed at some time in their lives, 181 (22%) had active asthma, and 224 (26%) reported current smoking. Participants with inactive asthma had pre- and postbronchodilator spirometry results comparable to those of participants who never had asthma. Participants with newly diagnosed asthma had lower forced expiratory volume in 1 second/forced vital capacity ratios, which were not bronchodilator responsive. Factors associated with newly diagnosed asthma, chronic asthma, or shortness of breath with wheezing at 22 years of age included female gender, parental asthma, late-onset (>3 years of age) wheeze, persistent wheeze, Alternaria mold sensitivity at 6 years of age, cold air bronchial hyperresponsiveness, and reduced air flow rates at 6 years of age. Seventy percent of participants with current asthma and 63% with newly diagnosed asthma reported episodes of wheeze before 6 years of age. Male gender was a significant indicator of asthma remission by early adulthood. The combination of Alternaria sensitivity and cold air bronchial hyperresponsiveness at age 6 years and persistent wheeze at age 6 years were strong predictors of chronic asthma at age 22 years.CONCLUSIONS. Children with transient early wheezing were at much less risk for chronic asthma that persisted through childhood or reappeared more intensely in early adult life, compared with children with persistent or late-onset wheezing. Women were twice as likely to have new asthma diagnosed between 16 and 22 years of age.REVIEWER COMMENTS. This comprehensive study confirms previous longitudinal studies of the same age group. The lack of bronchodilator response of the forced expiratory volume in 1 second in newly diagnosed asthma is disconcerting but does not necessarily reflect permanent obstruction. Initial oral corticosteroid treatment has been shown to improve pulmonary function and to unmask bronchodilator responsiveness. Limitations of the study include the use of physician-diagnosed asthma in the absence of the demonstration of bronchodilator reversibility, a significant loss of participants over the course of time, with resulting skewed participant demographic characteristics, and selected assessment of responses to cold air. No risk factor alone identifies all of the possible forms of asthma.

Natural killer T cells regulate the development of asthma

Studies in mice, monkeys and humans suggest that invariant natural killer (iNK) T cells play a very important role in the pathogenesis of asthma, a heterogeneous disease associated with airway inflammation and airway hyper-reactivity. The requirement for iNK T cells in multiple mouse models of asthma is novel and surprising, challenging the prevailing dogma that CD4+ T cells responding to environmental allergens are the key cell type in asthma. In this article, we examine the recent studies of iNK T cells and asthma, and discuss how different subsets of NK T cells function in different forms of asthma, including forms that are independent of adaptive immunity and Th2 cells. Together, these studies suggest that iNK T cells, which can interact with many other cell types including Th2 cells, eosinophils and neutrophils, provide a unifying pathogenic mechanism for many distinct forms of asthma.

Itraconazole for severe asthma with fungal sensitivity

Background: Severe asthma with fungal sensitivity (SAFS) is a recently described form of asthma that is difficult to treat with conventional inhaled corticosteroids. Antifungal therapies such as itraconazole might be an option. Objective: To discuss the data from a study evaluating efficacy and safety of itraconazole therapy in SAFS. Methods/results: Itraconazole therapy was found to improve quality of life and reduce immune response, with no impact on lung function. Conclusions: Itraconazole may be a promising therapy in SAFS, provided its potential of reducing airway inflammation is further documented.

Endoscopic sinus surgery and asthma outcomes

Introduction: Chronic rhinosinusitis (CRS) is often associated with bronchial asthma, and the presence of rhinosinusitis aggravates asthma course, although well-controlled studies to support such a statement are lacking. More convincing evidence for a sinobronchial relationship comes from observations that the clinical course of asthma improves after medical treatment of concurrent rhinosinusitis. Furthermore, patients with asthma may be unresponsive to therapy until coexisting sinus disease is successfully treated. Endoscopic sinus surgery (ESS) has been suggested to have favorable effects on associated bronchial asthma, thus reducing the need for long-term asthma medications in patients with sinusitis and asthma. Unfortunately, most studies addressing this problem are retrospective and poorly controlled; thus, evidence for a causal relationship between sinusitis and asthma is not clear cut. In a subpopulation of patients with asthma and rhinosinusitis, aspirin (ASA) and other NSAIDs induce acute asthmatic and nasal symptoms. Patients with ASAexacerbated respiratory disease typically suffer from a particularly severe form of asthma. High recurrence of nasal polyps and the frequent need for sinus surgery are characteristic of this group of patients. Previous studies have not provided equivocal evidence for greater clinical benefi t of endoscopic nasal surgery on asthma outcomes in ASA-sensitive versus ASA-tolerant asthmatics.

Relationship between atopic asthma and the population prevalence rates for asthma or atopy in children: Atopic and nonatopic asthma in epidemiology

Innumerable articles have tried to solve the "continuing enigma of atopic and nonatopic asthma" but notwithstanding the strenuous efforts to substantiate the few well-known clinico-epidemiologic differences between these two forms of asthma most studies have hitherto generated inconclusive statements. In a recent study based on the review of epidemiologic studies conducted worldwide in unselected populations of children, we documented that the prevalence of atopic asthma (AA) was high in the populations with a high prevalence of atopy. We systematically reviewed 36 articles that studied 48 populations of unselected children and reported prevalence rates for asthma and atopy in the total sample and in the subpopulations. No significant difference was found in the prevalence of asthma cases in the quartiles of childhood populations subdivided for the prevalence of atopy. In addition, atopy did not increase significantly in the subgroups of populations subdivided by asthma quartiles. In both subgroups, however, AA increased with increasing atopy or with increasing asthma (p < 0.001). Using a positive skin-prick test reaction to define cases of asthma as cases of AA is misleading because the prevalence of subjects so defined is heavily influenced by the environmentally generated changes in the prevalence of atopy or asthma. Asthma in a child should be labeled as a case of AA only if skin-prick tests yield a positive reaction and the clinical history documents asthma symptoms triggered by allergen exposure.

Diagnosis and treatment of allergic bronchopulmonary aspergillosis

Allergic bronchopulmonary aspergillosis (ABPA) is a rare form of asthma that is most common in corticosteroid-dependent asthmatic patients and cystic fibrosis patients. It is caused by an abnormal T-helper class 2 response of the host to Aspergillus antigens. Although signs and symptoms of typical asthma are usually present with ABPA, unusual features such as fever, expectoration of brown plugs, and central bronchiectasis with or without mucoid impaction on chest radiographs may be present. ABPA is important to diagnose because inadequate therapy may lead to permanent lung destruction. Corticosteroids are the drug of choice for ABPA; however, the doses required are often greater than for routine asthma and corticosteroid dependence is not unusual. Azole therapy appears to have an adjunctive role in treatment in terms of improving signs and symptoms of the disease and demonstrating a corticosteroid-sparing effect.

Minor psychiatric disorders in mothers and asthma in children

Recent studies have shown that asthma represents a major health issue not only in children of developed countries but also in urban centers in some middle-income countries. Brazil has one of the highest prevalences of asthma worldwide. Recently, interest has grown in the relationship between psychosocial factors and asthma. This article examines the relationship between maternal mental disorders and the prevalence of asthma in low-income children from an inner city area of Salvador in the state of Bahia, Brazil, and is part of the SCAALA program (Social Change, Allergy and Asthma in Latin America). A total of 1,087 children between the ages of 5 and 12 were investigated, together with their mothers. The mothers' mental health was evaluated using the SRQ-20, an instrument for the psychiatric screening of minor psychiatric disorders (depression, anxiety and somatic complaints). The prevalence of asthma was investigated using the ISAAC survey, a standardized, validated questionnaire for asthma and other allergic diseases. Cases were defined as asthma if the patient reported having had wheezing in the previous 12 months in addition to at least one of the following: having asthma, wheezing while exercising, waking during the night because of wheezing, or having had at least four episodes of wheezing in the previous 12 months. Atopy was defined as a positive skin prick test to allergens. The presence of minor psychiatric disorders in the mothers was significantly associated with the presence of asthma in the children, and this association was consistent with all forms of asthma, irrespective of whether it was atopic or nonatopic. Future studies should be carried out to further investigate this association and the potential biological mechanisms involved. Programs for asthma control should include strategies for stress reduction and psychological support for the families of asthmatic children.

Advances in Neutrophil Biology: Clinical Implications

Many lung diseases are characterized by neutrophil-dominated inflammation; therefore, an understanding of neutrophil function is of considerable importance to respiratory physicians. This review will focus on recent advances in our understanding of how neutrophils are produced, how these cells leave the circulation, the molecular events regulating neutrophil activation and, ultimately, how these cells die and are removed. The neutrophil is now recognized as a highly versatile and sophisticated cell with significant synthetic capacity and an important role in linking the innate and adaptive arms of the immune response. One of the key challenges in conditions such as COPD, bronchiectasis, cystic fibrosis, and certain forms of asthma is how to manipulate neutrophil function in a way that does not compromise antibacterial and antifungal capacity. The possession by neutrophils of a unique repertoire of surface receptors and signaling proteins may make such targeted therapy possible.

Toll-like receptor (TLR)-based networks regulate neutrophilic inflammation in respiratory disease

The neutrophil is a crucial early defence against microbial infection, but neutrophilic inflammation can result in devastating acute and chronic inflammatory diseases. In the lungs, the neutrophil is a principal part of the pathology of the acute respiratory distress syndrome, and its activation may also be of substantial importance in chronic obstructive pulmonary disease and some forms of asthma. Induction of neutrophil recruitment in response to microbial attack requires activation of TLR (Toll-like receptor)-based signalling pathways and the concerted actions of multiple cell types, including sentinel cells such as monocytes and macrophages acting together with tissue cell types such as the epithelium or smooth-muscle cell. The present review describes some of these networks and the resulting potential for their targeting in respiratory disease.

Occupational Health: Agriculture–COPD Link Bolstered

Smoking is typically considered the cause of 80–90% of chronic obstructive pulmonary disease (COPD) cases, but another significant known source is occupational exposure. Among the suspect occupations is farming, for which there has long been limited evidence of a risk for various respiratory diseases, including COPD. That link has been bolstered by an Austrian study, based on clinical evidence, published in the June 2007 issue of the American Journal of Industrial Medicine. “This is really the first study that shows a clear association confirming the agricultural risk,” says Alfred Munzer, director of pulmonary medicine at Washington Adventist Hospital in Takoma Park, Maryland, who did not participate in the study. Other studies have generally been much smaller or observational, he adds. Lead author Bernd Lamprecht, a pulmonologist at Paracelsus Medical University in Salzburg, says this is the first population-based study to evaluate COPD on the basis of measured postbronchodilator lung function, in combination with questionnaire data on occupational exposure. In the study, the team evaluated 1,258 Salzburg-area residents aged 40 and older, and found that 23% had any type of farming experience (farms in the area tend to be small, with a mix of various crops and animals). Substantially fewer farmers (46.2%) than non-farmers (54.6%) were current or former smokers. But 30% of the farmers had at least mild COPD, as determined by spirometer measurements of lung function before and after inhalation of a bronchodilator drug, compared with 22% of the nonfarmers. Using criteria for more severe COPD, the relative difference was even greater, with 14% of farmers and 8% of nonfarmers impaired. For mild COPD, the differences began showing up at about age 50, and held beyond age 80; corresponding data for more severe COPD were not reported. The authors acknowledge numerous limitations of their study, such as the lack of information on the type, duration, and intensity of exposures for the farmers, the limited range in geography and farm type, and the lack of long-term spirometry data for the study subjects. They could not speculate on what exposures may have caused the elevated COPD, but note that other studies have linked agricultural dusts with various respiratory problems. Another important consideration is that the method of classifying COPD used in the study is relatively new and has not been validated against the methods historically used to apply a COPD diagnosis, says Neil Schachter, a professor of medicine in pulmonary and critical care at Mount Sinai Medical Center. The new criteria were developed by the WHO and the National Heart, Lung, and Blood Institute through their Global Initiative for Chronic Obstructive Lung Disease (GOLD) and were released in 2001. The criteria are designed to provide more rigorous guidelines for a COPD diagnosis, putting substantial emphasis on spirometry results and relying less on patient history, symptoms, other tests, and a doctor’s judgment, as has been the case to date. Schachter points out that 5% of all the study subjects, both farmer and nonfarmer, reported having a doctor’s diagnosis of COPD, which is far lower than the 30% and 22% numbers reported by Lamprecht’s team. This finding highlights the long-running controversy over how to diagnose COPD, and what specific disease labels—such as emphysema, chronic bronchitis, some forms of asthma, and hypersensitivity pneumonitis—should be included under the COPD umbrella. Nonetheless, with COPD the fourth leading killer worldwide, identifying the causes of this disease is an important task. The limitations of the Austrian study need to be addressed, but Schachter says, “I think they found a real phenomenon: farmers are a high-risk category.”

Immunoglobulin constant heavy G subclass chain genes in asthma and allergy

The IGHG (ImmunoGlobulin constant Heavy G chain) genes are situated close to the IGHE gene on chromosome 14q32, 5'mu, delta, gamma3, gamma1, alpha1, gamma2, gamma4, epsilon, alpha2, 3', in linkage disequilibrium. The polymorphism of gamma3, gamma1 and gamma2 genes, is investigated as alternative allotypes. They are inherited in a Mendelian fashion and are expressed randomly in allelic exclusion. The alternative and functionally different gamma3, gamma1 and gamma2 gene variants, are found in four IGHG haplotypes, coding 4 B-cell variants: IGHG*bfn (=B1-cells), IGHG*bf-n (=B2-cells), IGHG*gan (=B3-cells) and IGHG*ga-n (=B4-cells). The dominance of the IGHG2*n allele from the IGHG*bfn haplotype (=B1-cells) has been shown in repeated investigations, namely in patients with asthma and allergy with increased serum levels of IgE > 600 ku/l and more often so in those with IgE > 1,000 ku/l or IgG4>1 g/l, in childhood asthma patients with mean level of IgE = 1,762 ku/l and in allergen exposed individuals developing laboratory animal allergy. In children with non-atopy and mean IgE level = 9.5 ku/l there is instead a dominance of the alternative allotypes from the IGHG*ga-n (=B4-cells) with IGHG2*-n alleles. In a case-control study allergic children with a family history of allergy, clinically manifest allergy and/or positive SPT, the IGHG*bfn haplotype (=B1-cells) with the IGHG2*n allele dominates, with increased risk of atopy and the IGHG*bf-n haplotype (=B2-cells) with the IGHG2*-n allele is infrequent with low risk, probably protective against atopy. The phenotypic expressions of the IGHG*bfn haplotype (=B1 cells) and IGHG*bfn/*bfn diplotypes (B1/B1-cells) are increased IgG2*n allotype together with increased IgE serum levels and IgE sensitisation in agreement with atopy. The alternative IGHG*ga-n/*ga-n diplotype (B4/B4-cells) express low IgG1*a- and IgG2*-n allotypes, together with low IgE and non-IgE sensitisation, in agreement with non-atopy. Together these studies have given us a greater understanding of the involvement of IGHG genes, IGHG coded B-cells and immunochemical and functional variants of IgG molecules describing different forms of asthma and allergy, which will improve diagnoses and treatment.