Food allergy and asthma

This feature focuses on recent nutrition studies that are relevant to clinical medicine. The basis for each discussion is an article from a notable medical or scientific journal. Dr Podell evaluates the findings presented and speculates about their implications for primary care.     

The risk of allergy in asthma

The prevalence of atopy among asthmatics is more than 70 per cent. Atopy is more prevalent among older children and young asthmatic adults. It is inherited, but the pattern of inheritance is not well defined. Increase in total IgE is one manifestation of atopy, and increase in IgE in early infancy is a predictor of atopic illness, including asthma. Sensitization to allergens and repeated exposure is one of the triggers of developing asthma in atopic patients. Allergy even without asthma (allergic rhinitis) is associated with an increase in bronchial reactivity. Allergy is a risk factor in occupational asthma and in exercise induced asthma. In fact, many non-asthmatic allergic rhinitis patients wheeze with exercise. Allergen avoidance and environmental control may contribute to the well-being of many asthmatics. Allergy hyposensitization (immunotherapy) may help control asthma in allergic patients.     

胰腺假性囊肿的治疗选择

目的对胰腺假性囊肿(PPC)不同的治疗方法进行疗效评估,并对PPC的治疗选择进行探讨。方法收集1998~2004年诊断为PPC的57例住院患者,依据治疗方法分为三组:保守治疗组、经皮穿刺引流(PCD)组、外科手术组,评估其疗效。结果保守治疗组28例,治疗有效率为68%;PCD组15例,治疗有效率为60%;外科手术组27例,总治愈率为81%,行囊肿空肠Roux-en-Y吻合术患者的治愈率为93%。结论保守治疗对于PPC的治疗有重要意义;安全有效的PCD术是有症状患者的较佳选择;外科手术依然是胰腺假性囊肿最有效的治疗手段。     

Gallstones: a choice of treatments]

This article presents a profile of the 20-year evolution in the treatment of gallbladder stones. The author herself works in a modern hepato-biliary and pancreatic surgical department of Hospital Saint-Luc in Montreal. The role of the gallbladder, its pathophysiology and the symptoms of gallbladder syndrome are explained. The main objective of the article is to inform the nurse that, along with traditional surgical treatment, other treatments, non-surgical as well as surgical, do exist. The general public is aware of new methods such as laparoscopic cholecystectomy. This surgical procedure is explained along with other choices of treatment.     

Evidence-based treatments for acute asthma.

Asthma is an important health care problem; over 12 million people in the United States suffer from asthma, the majority of whom are young patients. Presentations of acute asthma to emergency departments are common. In the United States, acute asthma presentations account for close to 2 million emergency department visits annually, and these patients often exhibit acute and chronic markers of severe asthma; so controlling asthma is important from many perspectives. We review the evidence for various acute asthma therapies, using the highest levels of evidence, employing systematic reviews (especially those from the Cochrane Collaboration) and evidence from randomized controlled trials to guide therapy decisions. beta agonists and systemic corticosteroids are the cornerstones of initial treatment. Delivery of beta agonists via nebulizer or metered-dose inhaler with spacer device appear to be similarly efficacious. However, recent evidence from studies involving children and adults indicate that addition of ipratropium bromide to early beta agonist treatments may reduce airway obstruction and reduce hospital admissions, especially for more severe asthma. Evidence from systematic reviews indicates that intravenous magnesium sulfate may provide similar benefits in severe asthma. Antibiotics, intravenous beta agonists, and intravenous aminophylline have been shown to add little and may increase adverse effects. Treatment for discharged patients should include systemic corticosteroids for 5-7 days, for all but the mildest asthma. Addition of inhaled corticosteroids should be considered for most patients, since evidence suggests that inhaled corticosteroids may reduce relapses and improve quality of life. Alternative treatments such as long-acting beta agonists and leukotriene antagonists remain unproven in this setting. Linking a discharge plan to close follow-up and asthma education (especially an action plan) needs to be encouraged. Acute asthma is a common problem and treatment has improved dramatically over the past 10 years. Employing the evidence-based practice outlined above should reduce the burden of acute asthma on patients and the health care system.     

Allergen avoidance in the treatment of dust-mite allergy and asthma.

House-dust-mite allergen is one of the primary causes of asthma. In many instances, asthma is an immunoglobulin gamma E mediated atopy (i.e., allergen-specific hypersensitivity) that leads to non-specific bronchial hyper-reactivity and subsequent symptom manifestations. These symptoms may range from an annoying cough to full-blown respiratory failure. Allergen-avoidance measures should be a primary mode of treatment for atopic asthmatics. This article focuses on the dust-mite allergen and its relationship to asthma. It details specific avoidance measures that should be implemented by the majority of asthmatics. Studies are cited that support the aggressive use of these measures to decrease allergen exposure, and to subsequently prevent or significantly reduce asthma symptoms. When health care providers have a better understanding of avoidance measures and the rationale underlying their use, these measures are more likely to be valued and given greater emphasis in education and treatment plans. Renewed emphasis on an immunomodulatory approach to asthma treatment may help to reverse the rise in asthma morbidity and mortality rates.     

儿童变应性哮喘螨脱敏疗法的健康教育和护理

目的：探讨变应原特异性免疫疗法。方法：以105例哮喘性鼻炎为对象，采用安脱达脱敏疫苗进行皮下注射，剂量由小到大，浓度由淡到浓，直至达到对该变应原耐受的最大维持量。通过规律的免疫注射使患儿能够适应外界致敏原。从而达到避免过敏症状的出现。结果：患儿免疫系统Th1和Th2趋于平衡，减轻其暴露在有该变应原环境下的过敏症状，提高过敏性疾病患者的生活质量。结论：安脱达脱敏疫茁对螨虫过敏患儿治疗有效。     

Soothing signals: transplacental transmission of resistance to asthma and allergy

The progressive rise in the prevalence of allergic diseases since the 1970s is widely attributed to diminished exposure to microbial stimuli, resulting in dysregulated immune functions during early life. Most studies investigating the mechanism behind this phenomenon have focused on postnatal microbial exposure. But emerging evidence suggests that such programming may also occur in the developing fetus as a result of microbial stimulation of the pregnant mother.

Susceptibility to allergic disease: the “hygiene hypothesis”

Current interest in the role of environmental microbial exposure as a determinant of susceptibility to allergic diseases dates back to the hallmark publication by Strachan (1989) introducing the hygiene hypothesis, which inferred from epidemiological evidence that shared infections between siblings during early life protected children against development of allergic disease. On page 2869 of this issue, Conrad et al. (2009) add a new twist to the hygiene hypothesis by showing that allergic risk can also be modulated by microbial exposure before birth. Mice born to dams that were exposed to bacteria during pregnancy were less likely to develop allergic responses than those born to unexposed mothers. And maternal Toll-like receptor (TLR) signals were required for the transmission of protection.

The hygiene hypothesis and immune development

Soon after Strachan''s publication, our group identified infancy as the life phase during which risk for primary allergic sensitization is greatest. These studies also uncovered a link between delayed postnatal maturation of adaptive immune function and genetically determined, increased risk for atopy (Holt et al., 1992). Notably, infants from atopic families who were at high risk for developing allergic disease had reduced numbers of immunocompetent CD4⁺ T cells in the circulation. Moreover clones from high-risk infants produced lower levels of cytokines, particularly Th1 cytokines, resulting in an overall Th2 bias. This suggested that the developmental process underlying the transition from the quiescent and relatively Th2-polarized fetal immune phenotype toward the more active and balanced pattern characteristic of mature adaptive immunity was intrinsically slower in the high-risk population, thus increasing the likelihood of priming Th2-biased immunity against environmental allergens (Holt et al., 1992). Although recent data from prospective studies on birth cohorts still support this general concept (Rowe et al., 2007), it is now clear that T cells are only one component of a complex mosaic of innate and adaptive immune mechanisms that are developmentally compromised in high-risk children (Holt and Sly, 2007).An obvious question arising from these findings is what drives immune maturation in early life. It is evident from studies on germ-free mice that the primary triggers for postnatal immune maturation is provided by microbial signals that are not available in the intrauterine environment, in particular from commensal bacterial (Holt, 1995) and possibly low-pathogenicity viruses (McIntire et al., 2003) in the gastrointestinal tract. It is now clear that respiratory viral pathogens exacerbate rather than retard diseases such as atopic asthma in children (Sly et al., 2008), reinforcing the emphasis on the gastrointestinal tract as the most likely site for generation of the protective, microbial-induced signals envisaged in the hygiene hypothesis. Indeed, a major international research effort has now developed to characterize the underlying immunological processes, and to identify strains of organisms with “safe” immunomodulatory properties for use as oral therapies in inflammatory diseases, with some (limited) success (Holt and Sly 2007).

Meanwhile, back at the farm…

This gut-centric view has been challenged by findings from landmark human studies relating to asthma and allergy in traditional farming communities. These epidemiological studies defined a unique gradient in allergy and asthma prevalence between children born into traditional farming families and their rural and urban counterparts, with the lowest prevalence occurring in the former. The hallmark characteristic of these farms is barns in which animals (especially dairy cows) are housed over the winter, during which much of the in-barn work is performed by the mother of the family. A series of studies (for review see von Mutius and Radon, 2008) have provided compelling evidence for a link between repeated exposure of the offspring of these farming mothers to microbe-rich barn environments during infancy and reduced susceptibility to subsequent allergy/asthma development, which is associated with persistent changes in various aspects of immune function in the children.The high microbial burden which appears to mediate protection in these infants is multifaceted and involves both gastrointestinal exposure to components in unpasteurized milk and exposure to high levels of LPS-containing dust (Braun-Fahrländer et al., 2002). Indeed, exposure to LPS in house dust also protects against the subsequent development of allergies in nonfarming settings (Gereda et al., 2000). It is interesting to note that farm exposure during infancy also modulates susceptibility to inflammatory diseases beyond allergy, including ulcerative colitis and Crohn''s disease (Bach, 2002; Radon et al., 2007).Perhaps a more unexpected finding was that exposure of mothers to the barn environment during pregnancy was also a major factor in modifying immune function and reducing risk of allergic disease in their offspring (Ege et al., 2008; von Mutius and Radon, 2008). Newborns of farm-exposed mothers displayed enhanced levels of regulatory T (T reg) cell activity at birth, which was associated with reduced Th2 cytokine production after cord blood stimulation (Schaub et al., 2009). Stimulated cord blood cells from these infants also showed increased expression of TLR2 and CD14, suggesting innate immune cell activation. In a parallel study, 5-13-yr-old children of farm-exposed mothers displayed reduced rates of sensitization and concomitantly increased TLR2, TLR4, and CD14 gene expression in PBMCs (Ege et al., 2006). It should be emphasized that the effects in the children were unrelated to the farm exposure levels at the time of their PBMC collection, and instead were related exclusively to the mothers'' exposures during pregnancy.

Transplacental immune programming

These findings raise the intriguing possibility that appropriate stimulation of the maternal immune system during pregnancy may generate signals capable of “educating” the fetal immune system to pave the way for efficient functional maturation after birth. Is this plausible? There is some evidence that supports prenatal programming, including data from birth cohort studies showing that neonatal patterns of cytokine production are significant predictors of subsequent risk for allergy and asthma (Macaubas et al., 2003). The general concept of signaling between the maternal and fetal immune systems is not new and encompasses fundamental protective mechanisms ranging from transplacental transfer of protective antibodies to allostimulation of tolerogenic T reg cells in the fetus by migrating maternal cells (Mold et al., 2008). However, in the human allergy/asthma field, the major focus has been on the converse scenario: maternal transmission of disease risk (Lim and Kobzik, 2009). The mechanisms involved in transmission of risk from mother-to-fetus are incompletely understood. Based on limited data from animal models, it has been speculated that transplacental transfer of Th2-trophic cytokines and/or cells from atopic dams may be involved (Matson et al., 2007).Conversely, a variety of experimental mouse models (for review see Lim and Kobzik, 2009; Matson et al., 2007) have demonstrated that stimulation of a strong Th1 environment during pregnancy can markedly reduce the susceptibility of the offspring to experimental asthma. This includes exposure to aerosolized LPS via the respiratory mucosa, which mimics some aspects of the human farm exposures discussed above. These data collectively suggest that maternal signaling to the fetal immune system exists on several levels and is likely to vary qualitatively depending on the stimuli present in the maternal environment.

Maternal farm exposure and asthma: a mouse model

Conrad et al. (2009) describe a mouse model designed to specifically examine the implications of maternal farm exposure. The group used a bacterial strain, Acinetobacter lwoffi, a common component of barn dust that has the potential capacity to protect against atopy. The progeny of mice given repeated intranasal treatments with A. lwoffi during pregnancy developed strong resistance to experimental atopic asthma development in response to subsequent sensitization and aerosol challenge with ovalbumin. Intriguingly, the resistance to eosinophilia, goblet cell hyperplasia, and airway hyperresponsiveness after challenge was independent of changes in specific IgE, which were not significantly reduced by the treatment. This finding is reminiscent of successful immunotherapy in humans in which reductions in symptoms typically precede decreases in IgE titers.The protective effect was dependent on intact maternal TLR signaling, as offspring of mice lacking multiple TLRs (TLR2, 3, 4, 7, and 9) generated allergic responses comparable to those seen in the offspring of nonexposed mothers. Exposure to A. lwoffi triggered a mild-to-moderate local inflammatory response in the lungs of wild-type animals, which was accompanied by the up-regulation of mRNA specific for TLR1, 2, 3, 5, 7, and 9, and the production of TNF, IL-12, and IL-6 in the BAL and serum. It was particularly notable that the lung response was also accompanied by down-regulation of TLR gene expression in the placenta, which the authors suggest occurs predominantly on the maternal side, with concomitantly reduced expression of a broad range of cytokine genes (Conrad et al., 2009). This TLR down-regulation could be partially reproduced in primary placental cultures treated with IL-6.These findings suggest that controlled microbial stimulation at the maternal mucosal surface (in this case, the respiratory tract) during pregnancy, at a level that elicits mild, subclinical inflammation, can generate diffusible signals that function as the immunological equivalent of a lullaby in placental tissue, dampening baseline innate immune activity and attenuating local cytokine production. The association between these effects and the subsequent resistance to allergic disease in offspring suggests that these changes at the fetomaternal interface had positive effects on functional maturation of the fetal immune system. It would be of interest to analyze the nature of these changes in follow-up studies and to determine whether exposure of the offspring to the same microbial stimuli after birth (as is the norm with the farm children) further amplifies their acquired resistance to allergy and asthma. It is noteworthy that Conrad et al. (2009) ruled out direct transfer of bacterial endotoxin as a significant factor in the antenatal programming process. It is also important to emphasize that although A. lwoffii is a potent mediator of the transplacental effects observed, there is no reason to believe that this organism is unique in this regard, and indeed the authors report qualitatively similar effects with other microbial agents.

In placenta veritas?

Homeostatic regulation of the immunological milieu of the placenta has traditionally been far removed from the normal purview of allergy/asthma researchers. However, the growing realization that the long-term programming of immunological and respiratory phenotypes that underpin these diseases is initiated during infancy (Holt et al., 2005) is fuelling interest in this area. The new findings reported by Conrad et al. will undoubtedly add to this interest.It is a widely accepted precept that maintenance of the placental microenvironment in a “noninflamed” steady state represents the ideal for healthy development of the fetus and that efficient local surveillance for microbial pathogens is central to fetal survival (Mor et al., 2005). How this balance is achieved remains largely unknown, but the cellular players in the game of fetal survival are essentially the same as those responsible for maintenance of immunological homeostasis in the airway mucosa, where they help to determine susceptibility versus resistance to allergy and asthma. In the maternal decidua, interactions between dendritic cells (DCs) and macrophages play a central role in maintaining tolerance to fetal antigens (Blois et al., 2007). The equivalent myeloid populations in the airway mucosa normally maintain tolerance to incoming aeroallergens (Holt et al., 2008), and it may thus be reasonable to extrapolate somewhat between the two organ systems.In this regard, DC populations in the airway mucosa are highly dynamic even in the steady-state, continuously shuttling antigen between the mucosal surface and the draining lymph nodes. These cells respond rapidly to inhaled microbial ligands, further amplifying local immune surveillance by increasing recruitment of bone marrow–derived immature DCs and, later, monocytes (Holt et al., 2008). This mechanism provides the essential local link between the innate and adaptive arms of the immune response and appears to be an essential component of host defense.Unless fine control of this process is maintained, however, the host response to microbial exposure can itself become pathological. An archetypal example of this is the demonstration that cytokine signals generated in the inflamed airways during virus-induced asthma exacerbations can induce proinflammatory functions in immature DCs and monocytes before their release from the bone marrow (Subrata et al., 2009). Moreover, inflammation-associated signaling from the periphery to the bone marrow can also program regulatory phenotypes in migratory myeloid cell populations (Gordon, 2003). Once released into the circulation, these myeloid cells are free to migrate into any tissue (including potentially the decidua) to subsequently modulate local immunological processes. It is thus possible that the effects observed in the mouse placenta by intranasal exposure to A. lwoffi may occur in part via this indirect route rather than exclusively by the direct passage of cytokines into decidual tissue itself (Fig. 1). It should be noted, however, that lymphangiogenesis in human decidual tissues is much more robust than in the mouse, and this is likely to influence migration and turnover of DCs and other myeloid cells (Collins et al., 2009). This difference may result in species differences in sensitivity to external stimuli such as those described here (Conrad et al., 2009), and this possibility needs to be addressed in follow-up studies. Despite this caveat, these findings have established a potentially important set of principles relating to maternal environmental exposure during pregnancy and subsequent immune functions in offspring that, if substantiated, will be applicable to a much broader range of disease than simply asthma and allergy.Open in a separate windowFigure 1.Proposed mechanisms by which maternal exposure to bacteria protects against allergies in offspring. Aerosol exposure to microbe-containing dust particles induces mild-to-moderate inflammation in the lungs, including increased expression of TLRs and production of cytokines. Cytokines might then enter the bloodstream and be delivered directly to the placental tissues, where they depress TLR expression, cytokine production, and influence resident myeloid cell functions. Circulating cytokines might also enter the maternal bone marrow, where they stimulate and “program” myeloid precursor cells. Programmed DCs and monocytes could then enter the circulation, and some of these cells could traffic to the decidua, where they could replace resident myeloid populations and influence the local inflammatory milieu.     

Inhaler devices for asthma and COPD: choice and technique

Nurses caring for patients with asthma or chronic obstructive pulmonary disease need a good basic knowledge of the types of inhaler devices available and which may suit, for example, a very young child, an active young person or an elderly patient with dexterity problems. This Study describes the advantages and disadvantages of some commonly prescribed devices.     

DNA vaccines for non-infectious diseases: new treatments for tumour and allergy

The last decade of DNA vaccine research was characterised by a pioneer spirit and enormous enthusiasm, with a large number of publications demonstrating the usefulness of this approach. Unfortunately, DNA vaccines have not necessarily met the high clinical expectations and a number of complications need to be overcome. In the case of cancer and allergy, the requirements for achieving the objectives are very different. Vaccines against allergies need to suppress or alter an unwanted immune response, while a cancer DNA vaccine has to overcome tolerance and/or immune suppression and initiate a powerful immune response. This review addresses currently used general optimisation strategies for DNA vaccines such as modification of immunisation regimens, improving the delivery systems and using molecular adjuvants. In addition, cancer-specific approaches, such as the stimulation of innate and adaptive immunity with replicase-based DNA vaccines, and targeting non-tumour-associated antigens (TAAs) are discussed. Specifically for the optimisation of DNA vaccination against allergies, procedures such as allergen gene recoding, T helper (Th)1 modulation, and the creation of safe DNA vaccines by gene fragmentation, ubiquitination or using artificial hypoallergens are being analysed. These strategies, individually or in combination, hold the potential of making DNA vaccines useful for application in the clinic.     

DNA vaccines for non-infectious diseases: new treatments for tumour and allergy

The last decade of DNA vaccine research was characterised by a pioneer spirit and enormous enthusiasm, with a large number of publications demonstrating the usefulness of this approach. Unfortunately, DNA vaccines have not necessarily met the high clinical expectations and a number of complications need to be overcome. In the case of cancer and allergy, the requirements for achieving the objectives are very different. Vaccines against allergies need to suppress or alter an unwanted immune response, while a cancer DNA vaccine has to overcome tolerance and/or immune suppression and initiate a powerful immune response. This review addresses currently used general optimisation strategies for DNA vaccines such as modification of immunisation regimens, improving the delivery systems and using molecular adjuvants. In addition, cancer-specific approaches, such as the stimulation of innate and adaptive immunity with replicase-based DNA vaccines, and targeting non-tumour-associated antigens (TAAs) are discussed. Specifically for the optimisation of DNA vaccination against allergies, procedures such as allergen gene recoding, T helper (Th)1 modulation, and the creation of safe DNA vaccines by gene fragmentation, ubiquitination or using artificial hypoallergens are being analysed. These strategies, individually or in combination, hold the potential of making DNA vaccines useful for application in the clinic.     

The choice, application and review of topical treatments for skin conditions

Topical treatments are essential in the management of skin conditions. However, for the nurse working outside the specialty of dermatology, knowing exactly what topical treatment to use, and where and when to apply it, can be extremely daunting.     

Latex protein allergy and your choice of gloves: a balanced consideration.

Natural rubber gloves have been acknowledged as the best protective devices available for protecting health care personnel and their patients against viral transmission and infectious fluids. Yet, with the adoption of standard safety precautions and the increase in the use of gloves, an increasing number of people are being affected with latex allergy. Negative publicity related to latex allergy has resulted in health care personnel deciding against using the highly protective natural rubber gloves. The relationship between natural rubber gloves and latex protein allergy needs to be better understood in order for health care professionals to make an informed choice in their selection of gloves.