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H J Malling

Publications and source records attributed to H J Malling.

At least 37 records · Page 2Linked to original sources
PubMed2000

Minimising the risks of allergen-specific injection immunotherapy.

The clinical advantages of allergen-specific immunotherapy are counterbalanced by the risk of inducing systemic adverse effects. Although the frequency of life-threatening systemic reactions is low, the treatment carries a risk of inducing anaphylactic reactions. A fundamental point in risk assessment is to use a clinically meaningful and internationally accepted grading system for reactions. Of importance in minimising the risk of systemic adverse effects is the identification of at-risk patients and factors, the institution of procedures for monitoring patients before injections, and the adjustment of dosages in accordance with defined rules. Asthma, especially uncontrolled asthma, is a significant risk factor for the induction of systemic reactions. Likewise, dose escalation during allergen exposure, i.e. during pollen seasons, increases the risk of adverse effects. It is recommended that standardised extracts with a documented potency and consistency between production batches are used in order to prevent overdose when changing to a new vial. The intensity of the induction regimen is a balance between the risk of inducing systemic reactions and the time required to administer the regimen. Single injections once a week are generally well tolerated, in contrast to rush immunotherapy which may carry an increased frequency of adverse effects. A clustered induction regimen (2 to 4 injections per visit) represents a compromise of a patient-friendly fast regimen without an unacceptably high frequency of systemic reactions. A major issue in improving the safety of allergen injections is minimising the human factor, e.g. mistakes of patient identification, allergen extracts and dosages. Meticulous care in monitoring every patient before the injection, which requires education and training of the staff in the dosage decision process, is the cornerstone in reducing adverse effects. Involving the patient actively in the safety monitoring process might be helpful and improves patient compliance by allowing the patient to be an active partner in the treatment. Finally, if anaphylactic reactions are induced, a successful outcome is related to the staff being able to identify the early signs and to institute immediate rescue treatment. A quality assurance programme is the optimal way to minimise the risk of immunotherapy-associated systemic reactions.

Allergens↗
PubMed1999

Cutting edge: expression of the NF of activated T cells in eosinophils: regulation by IL-4 and IL-5.

We report that NF-AT1 and NF-AT4 are expressed cytoplasmically in resting eosinophils, whereas NF-AT2 and NF-AT3 have not been seen. Likewise, NF-AT1 mRNA and NF-AT4 mRNA have been detected in resting eosinophils, and their levels can be significantly up-regulated by the Th2-associated cytokines IL-4 and IL-5. There is no detectable NF-AT protein expression in the nuclei of resting eosinophils. However NF-ATs appear in the nuclei of IL-4-, IL-5-, or ionomycin-stimulated eosinophils. Only NF-AT1 and NF-AT4, but not NF-AT2 and NF-AT3, have translocated into the nuclei in IL-4- or IL-5-stimulated eosinophils. These findings delineate a novel pathway in the cytokine network in which Th2 lymphocytes "control" eosinophils via the release of IL-4 and IL-5, and activation of NF-AT in eosinophils. The findings also suggest that a later feedback "talking" may exist between eosinophils and Th2 lymphocytes.

DNA-Binding Proteins↗
PubMed1999

[Specific immunotherapy (hyposensitization) in allergic rhinoconjunctivitis. Meta-analysis of effectiveness and side effects].

BACKGROUND: Specific immunotherapy (SIT) of allergic disorders as introduced by Freeman and Noon involves the application of gradually increasing doses of extracts of the material to which the individual is sensitive. SIT represents the only specific treatment that can be offered to allergic patients besides allergen avoidance. SIT has been widely used in patients with pollen allergic rhinitis and its clinical efficacy has been demonstrated in several controlled clinical trials. The underlying mechanism of this treatment is still not understood. Previous studies have focused on changes in serum antibodies, including blunting of seasonal rises in specific IgE and increases in specific IgG antibodies, especially of the IgG4 isotype. Recent studies have suggested an effect on T-lymphocytes, leading to a switch from a predominant Th2 response--that is, interleukin (IL)-4 and IL-5--to a Th1 response involving interferon (IFN)-gamma. The switch of a cytokine profile to a predominant IFN-gamma response results in inhibition of IL-4 dependent IgE production, which is reinforced by a decrease in the production of IL-4 by Th2 cells. METHODS: In the present study a meta-analysis was performed to evaluate all double-blind placebo-controlled studies investigating the effect of SIT on clinical and immunological treatment used in patients with allergic rhinoconjunctivitis. RESULTS: SIT was shown to be an effective treatment modality in allergic rhinoconjunctivitis, decreasing symptoms, the need for medication and reactivity in specific nasal and conjunctival provocation tests, as well as inflammatory markers. Histologically, a switch might be induced from a predominant Th2 cell profile to that of a Th1. CONCLUSIONS: In general, the efficacy of SIT is dependent on the allergen the individual patient is sensitive to, the quality and total amount of the allergen applied and the SIT schedule.

Conjunctivitis, Allergic↗
PubMed1999

Histamine and tryptase in nasal lavage fluid after allergen challenge: effect of 1 week of pretreatment with intranasal azelastine or systemic cetirizine.

BACKGROUND: Antihistamines (H1-receptor antagonists) act by competitive antagonism of histamine at H1-receptors. In addition, high concentrations of some antihistamines inhibit allergen-induced histamine release from mast cells in vitro. OBJECTIVE: The purpose of this study was to determine the effect of intranasal azelastine or systemic cetirizine (both potent antihistamines) on the allergen-induced release of mast-cell mediators from the human nasal mucosa in vivo. METHODS: Patients allergic to birch pollen (n = 11) and control subjects not allergic to birch pollen (n = 5) were included in a randomized, double-blind, placebo-controlled, 3-way crossover study outside the pollen season. Each subject was treated with azelastine nasal spray 0.14 mg per nostril twice daily, cetirizine tablets 10 mg every day, or placebo for 1 week using a double-dummy design. At the end of each treatment period, nasal allergen challenges were performed, and the number of sneezes were counted. In addition, nasal lavage fluid was collected, and the levels of mast-cell mediators (histamine and tryptase) were measured. RESULTS: The allergen challenge of patients allergic to pollen produced sneezing and a significant increase in the levels of histamine and tryptase. The challenge of subjects not allergic to pollen produced no such response. Azelastine and cetirizine significantly reduced allergen-induced sneezing and the associated increase in histamine and tryptase levels. No significant differences were found between the azelastine and cetirizine treatments. CONCLUSION: Pretreatment with azelastine or cetirizine inhibits the allergen-induced release of mast-cell mediators from the human nasal mucosa. Our results are consistent with the hypothesis that both antihistamines reduce mediator release from nasal mucosa mast cells in vivo. However, further studies are necessary to test this hypothesis.

Administration, Intranasal↗
PubMed1999

[Methods for monitoring of therapeutic efficacy in immunotherapy of allergic rhinitis].

Efficacy monitoring of immunotherapy (IT) is performed to adjust the therapy according to the patient's reactions, to collect data for scientific studies and to evaluate the efficacy of IT. A decrease of allergy symptoms and of drug use are the main parameters. For this, allergy diaries are most suitable. Pollen exposition should be monitored with Burkhard traps. Wheal and flare reactions in skin tests can be measured by visual inspection with quantification of the diameter on transparent foils or by means of laser scanners. Nasal provocation testing leads to subjective and objective (rhinomanometry, acoustic rhinometry) results. A change in the threshold concentration of allergen, which is needed to provoke a positive test reaction, can be used to evaluate the success of an IT. Additionally, systemic or local side-effects should be carefully revealed. Cytologic measures can be achieved by nasal lavages. Cotton samplers, cytology brushes and suction techniques are used to collect cells and nasal secretions. Early and late allergic reactions can be evaluated. Specific cell activation markers like ECP or tryptase are useful parameters in nasal secretions. T-lymphocyte subpopulations and T-cell-lymphokine-profiles can be detected. During IT, a change from a dominating TH2-cytokine-profile to a dominating TH1-cytokine-profile can be seen. For the reason of their expense, those methods are restricted to scientific investigations and only rarely used for routine diagnostics.

Biomarkers↗
PubMed1999

[WHO position paper (summary)--allergen-immunotherapy: therapeutic vaccines for allergic diseases].

From January 27 to 29, 1997, experts on allergen immunotherapy from various geographic locations throughout the world met at the headquarter of the World Health Organization (WHO) in Geneva, Switzerland to reach a consensus on international guidelines. Guidelines or indications for immunotherapy with inhalant allergens and venoms have been published before by the WHO, the European Academy of Allergy and Clinical Immunology (EAACI), the International Consensus Report on Asthma, the Global Strategy for Asthma Management and Prevention, the International Consensus Report on Rhinitis, the British Society for Allergy and Clinical Immunology, the American Academy of Allergy, Asthma and Immunology (AAAAI) and the American College of Allergy, Asthma and Immunology (ACAAI). The committee wrote a position paper based on scientific articles reviewed for data before April 1, 1997. These guidelines should result in a better understanding of the science and rationale for using allergen immunotherapy as well as improve the safety of such therapy. The document also defines new techniques being developed which may result in better efficacy and less risk for allergen immunotherapy as well as recommends areas of additional and necessary research.

Allergens↗
PubMed1998

Allergen immunotherapy: therapeutic vaccines for allergic diseases. A WHO position paper.

The World Health Organization and various allergy, asthma, and immunology societies throughout the world met on January 27 through 29, 1997, in Geneva, Switzerland to write guidelines for allergen immunotherapy. Over the ensuing year, the editors and panel members reached a consensus about the information to include in the WHO position paper "Allergen immunotherapy: Therapeutic vaccines for allergic diseases." The historical term allergen extract was changed to allergen vaccine to reflect the fact that allergen vaccines are used in medicine as immune modifiers. The document summarizes the scientific literature and rationale for the appropriate use of such therapy to treat allergic rhinoconjunctivitis, allergic asthma, and Hymenoptera hypersensitivity. It also includes recommendations to improve safety, discusses new techniques being developed that may result in better efficacy and less risk, and offers recommendations for areas of additional and necessary research.

Allergens↗
PubMed1998

Histamine and tryptase in nasal lavage fluid following challenge with methacholine and allergen.

BACKGROUND: The level of histamine in nasal lavage fluid has been used as an index of mast cell/basophil activation in a number of studies. Obviously, such an index can only be valid if changes in the secretory activity of nasal glands do not affect the level of histamine in lavage fluid (i.e. hypersecretion, without a simultaneous activation of mast cells/basophils in the nasal mucosa, must not increase the level of histamine). OBJECTIVES: To asses the effect of nasal hypersecretion on histamine levels in lavage fluid. METHODS: Nasal challenges were performed with methacholine and allergen in grass pollen-allergic patients and non-allergic controls. Nasal lavage fluid was collected before and repeatedly for nine hours after nasal challenge, and the level of histamine was compared with that of a specific mast cell-derived enzyme, tryptase. In addition, the effect of methacholine on basophils was examined in vitro. RESULTS: Allergen challenge of allergic patients produced sneezing and a significant increase in histamine and tryptase levels, whereas challenge of non-allergic subjects produced no such response. Interestingly, challenge with methacholine also induced a significant increase in histamine levels. This increase was seen in both allergic and non-allergic subjects and it was not associated with any sneezing or increase in tryptase levels, indicating that mast cells were not activated. Furthermore, stimulation of basophils with methacholine did not induce any histamine release in vitro. CONCLUSIONS: Apparently, there exists a pool of histamine in the human nose that can be transferred to lavage fluid during glandular hypersecretion. The source of this histamine is yet to be identified. As the level of histamine seems to be affected by the secretory activity of nasal glands, we question the use of this single mediator as an index of mast cell/basophil activation in nasal lavage studies.

Administration, Intranasal↗
PubMed1998

Local immunotherapy.

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Drug Administration Routes↗
PubMed1998

IL-8 and the activation of eosinophils and neutrophils following nasal allergen challenge.

BACKGROUND: A growing body of evidence suggests that proinflammatory cytokines play a role in allergic inflammation by attracting and activating inflammatory cells. In this study, we have investigated the relationship between interleukin-8 (IL-8) in nasal lavage fluid and the local activation of eosinophils and neutrophils following nasal allergen challenge of allergic patients. METHODS: Nasal challenges were performed with grass pollen extract in 14 allergic patients and 5 nonallergic controls. Nasal lavage fluid was collected repeatedly for 10 h, and the levels of eosinophil cationic protein (ECP) and myeloperoxidase (MPO) were used as markers of eosinophil and neutrophil activation, respectively. The levels of these molecules were compared with that of IL-8 in nasal lavage fluid. RESULTS: Allergen challenge of allergic patients produced a significant late-phase increase in the levels of ECP and MPO. Furthermore, the level of MPO showed a highly significant correlation with the level of IL-8 in lavage fluid (r = 0.8, p< 0.0001), whereas there was no significant relationship between the levels of ECP and IL-8. CONCLUSION: Interestingly, our findings suggest that both eosinophils and neutrophils are activated following nasal allergen challenge. In addition, our results are consistent with the hypothesis that IL-8 acts as a chemoattractant/activator of neutrophils during the late phase of the allergic inflammation. In contrast, we were not able to demonstrate any significant relationship between the level of IL-8 in lavage fluid and the activation of eosinophils.

Adult↗