A. A. Wanderer
The histopathology of severe persistent asthma and chronic obstructive pulmonary disease is predominantly characterized by neutrophilic inflammation. It is posited that chronic hypoxia from hypoventilation in combination with hypoperfusion and hypercapnia are associated with induction of pulmonary tissue acidosis in SPA and COPD, which in turn provide ideal conditions to induce danger-associated molecular patterns, i.e., crystallized and calcium pyrophosphate. These stimuli in combination with other danger-related biochemical signals are capable of stimulating an innate immune receptor (cryopyrin inflammasome, NALP3) and cause interleukin-1β secretion with subsequent neutrophilic inflammation. There is evidence to suggest that the mechanisms and pathobiology associated with chronic hypoxia, reduced perfusion and reoxygenation in SPA/COPD may exhibit similarities to the biphasic pathobiology involved in ischemia-reperfusion injury. A rationale is suggested for trials of IL-1β targeted therapies as an adjunct strategy to control neutrophilic inflammation in these conditions.
A. Weissler, Y.A. Mekori, A. Mor
R. J. Martin
Asthma is an airway disease, yet that airway extends all the way to the alveolar tissue area. Pathohistiological as well as physiological and clinical studies have recently documented this aspect of asthma. The implications of this are important for all asthmatic patients, but particularly for those whose asthma is more difficult to control. Many of the inhaled preparations used as therapy for asthma are of relatively large particle size.
Thus, the deposition of these medications is mainly in the central and medium sized airways and very little of a given actuation gets to the distal airways. Ultrafine inhaled steroid particles have been shown to reach the more peripheral portions of the airway, and improvement in outcome variables such as air trapping as well as symptomatic outcomes have been demonstrated. This review focuses on anatomic airway changes, physiological changes of the distal airways, clinical outcome data, and particle size of inhaled preparations.
A. Reshef, I. Leibovich, A. Goren
Hereditary angioedema is a rare genetic disorder, manifested by recurrent edema leading to disfigurement, organ dysfunction and life-threatening respiratory impairment that may become fatal. The hallmark of HAE is a C1 esterase inhibitor deficiency, but recent evidence points at bradykinin as the main mediator that causes hyperpermeability of small vasculature, leading to accumulation of edema fluid. Current therapeutic options for HAE are limited, and consist of drugs, replacement therapy, and supportive treatment. In view of many disadvantages of the current therapeutic modalities new approaches to the treatment of HAE are now being offered. This review summarizes our experience with a new line of medications developed for the treatment of acute exacerbations and prophylaxis of HAE – icatibant: bradykinin receptor antagonist, ecallantide: kallikrein inhibitor, and two C1 INH preparations: Berinert-P, human plasma-derived concentrate, and Rhucin: novel recombinant C1-INH produced in transgenic rabbits. Preliminary results of these studies are encouraging and may bring new hope to the patients with this distressing condition. The exact number of HAE patients in Israel is unknown and because patients are treated individually and comprehensive laboratory assessment is partial, many cases might be missed or not treated according to accepted guidelines. We offer a new specialty center for HAE patients, addressing the medical and psychosocial needs of patients and their families.
Y. Waisel, A. Eshel, N. Keynan, D. Langgut
The pollen of Ambrosia (ragweed) is one of the major causes of pollen-induced allergy worldwide. This family of plants has apparently evolved in North America but was later spread into Europe and Asia. Flowering of the Ambrosias starts in mid-July and continues throughout the autumn and is a cause of major morbidity to allergic sensitized patients. The invasion of new species of Ambrosia into Israel is still in progress. Plants of Ambrosia artemisiifolia (American short ragweed), Ambrosia trifida (American giant ragweed), Ambrosia confertifolia, Ambrosia grayi and Ambrosia tenuifolia are increasingly found in Israel, mainly in the Hula valley in the eastern Galilee and near the Alexander River in the Sharon plain. From experience it is known that the time it takes to eradicate a new invasive species is limited. Action should be taken immediately or this new invasion will spread and cause a significantly increased burden of morbidity and increased health costs in Israel.
V. Gazit, D. Tasher, A. Hanukoglu, Z. Landau, Y. Ben-Yehuda, E. Somekh, I. Dalal
Background: Insulin-dependent diabetes mellitus is dominated by a Th1 response whereas atopic diseases such as asthma, eczema and allergic rhinitis are characterized by a Th2 response. Because it is known that Th1 and Th2 cells reciprocally counteract each other, it can be speculated that the prevalence of Th2-mediated diseases is lower in patients with a Th1-mediated disease.
Objectives: To compare the prevalence of atopic diseases among children with IDDM and age-matched controls.
Methods: The study group comprised 65 children with IDDM attending the pediatric endocrinology clinic at the Wolfson Medical Center. The control group consisted of 74 non-diabetic children who presented at the emergency room due to an acute illness (burns, abdominal pain, fever, head trauma). Patients were asked to complete a detailed questionnaire on their history of personal and familial atopic and autoimmune diseases. In addition, a total serum immunoglobulin E concentration and the presence of IgE antibodies to a panel of relevant inhalant allergens were analyzed.
Results: Children with IDDM and their first-degree relatives had a significantly higher prevalence of other autoimmune diseases such as thyroiditis and celiac as compared to controls. The two groups had a similar prevalence of atopic diseases with respect to history, total serum IgE, or the presence of IgE antibodies to a panel of relevant inhalant allergens.
Conclusions: The prevalence of atopic diseases in IDDM patients was similar to that in the normal population. Our results suggest that the traditional Th1/Th2 theory to explain the complexity of the immune response is oversimplified.
M. Rottem, D. Shostak, S. Foldi
Background: Cow's milk allergy is the most prevalent food hypersensitivity, affecting 2–3% of infants, but it tends to resolve with age. Cow’s milk-specific immunoglobulin E in the serum is an important measure in the diagnosis and follow-up of infants and children with cow's milk allergy.
Objectives: To examine the relation between CmsIgE and the probability of resolution of milk allergy.
Methods: CMsIgE was determined in the serum of 1800 infants and children referred for the evaluation of possible milk allergy. All children with CmsIgE of 1 kU/L or above were followed at the allergy clinic and, according to their condition, underwent milk challenge. The diagnosis of cow's milk allergy was made on the basis of a significant and specific history or a positive oral food challenge. Subsequently, oral tolerance was defined as an uneventful oral challenge.
Results: A total of 135 infants and children had milk-specific IgE greater than 1 kU/L. Forty-one percent of children still had clinical milk allergy after the age of 3 years. Sixty-eight percent of children older than 3 years with persistence of cow's milk allergy had milk-specific IgE > 3 IU/ml before the age of 1 year. Furthermore, 70% of children who at 3 years old had resolved their cow's milk allergy had milk-specific IgE that was lower than 3 IU/ml before the age of 1 year. The positive predictive value of CmsIgE > 3 IU/ml to persistent cow's milk allergy at age 3 years was 82.6% (P = 0.001), with a sensitivity of 67.9% and specificity of 70.4%.
Conclusions: Milk-specific IgE concentration in the first year of life can serve as a predictor of the persistence of milk allergy.
S. Halevy, N. Grossman
Background: Multiple drug allergy syndrome is a rarely reported clinical condition characterized by an adverse reaction to more than one different class of pharmacologically and structurally unrelated drugs. The pathogenesis may involve immediate-type or delayed-type hypersensitivity.
Objectives: To further characterize patients with MDA in terms of the type of CADR, drug intake and clinical drug suspicion.
Methods: The study group comprised 12 patients (6 males, 6 females) with CADRs showing in vitro drug-induced IFNγ release for multiple drugs, suggesting the presence of MDA. The diagnostic role of in vitro IFNγ release in identifying the culprit drugs was evaluated in terms of clinical data and the results of in vivo tests (withdrawal and/or challenge tests) with the offending drugs.
Results: Clinical relevance was attributed to in vitro drug-induced IFNγ release towards multiple drugs in this series of 12 patients with a variety of CADRs, implying MDA. The results of in vivo tests for the offending drugs confirmed the diagnosis. The main causative agents responsible were antibiotics and non-steroidal anti-inflammatory drugs.
Conclusions: The study further supports the role of a T cell-mediated mechanism in the pathogenesis of MDA. The in vitro drug-induced IFNγ release test may serve as a laboratory tool to identify the culprit drugs associated with this allergy.
Y. Zeldin, Z. Weiler, E. Magen, L. Tiosano, M. I. Kidon
Background: Subcutaneous allergen immunotherapy is effective in treating allergic airway disease. Disadvantages include immediate local and systemic adverse reactions and poor compliance.
Objectives: To obtain real-life efficacy and safety data through a prospective observational study of SIT in the allergist's office.
Methods: We prospectively collected data from all patients with a diagnosis of allergic rhinitis and/or asthma and a specific immunoglobulin E-mediated sensitization to one or more aeroallergens who began SIT during the 2 year period 1 January 2005 to 31 December 2006. As part of the routine immunotherapy care patients were asked to complete a disease activity questionnaire before and yearly during the treatment. The primary outcome measure was the combined rhinitis and asthma symptoms scores. Data from patients completing at least 1 year of immunotherapy were analyzed.
Results: Altogether, 133 enrolled patients with a mean age of 22.7 years completed at least 1 year of SIT. The allergic rhinitis and asthma disease activity score decreased from a mean of 8.1 to 3.3 (rhinitis) and from 4.8 to 2.4 (asthma) on a 10 cm visual analogue scale after 1 year of SIT (P < 0.001 for all comparisons). Rhinitis medication use in all patients and asthma medication use in asthmatics decreased significantly. Mild local adverse reactions were almost universal. There were 11 patients (8%) who developed 14 immediate systemic, mild to moderate reactions. All reactions were successfully treated in the clinic; none required additional observation or hospitalization.
Conclusions: In the hands of experienced allergists subcutaneous allergy immunotherapy is a safe and efficacious option for patients with allergic rhinitis and asthma.