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Notes: The effect of the leukotrienes LTB4, LTC4 and LTD4 on the production of the lymphokine leukocyte migration inhibitory factor (LIF) from human peripheral blood mononuclear cells was tested. LTC4 and LTD4 failed to influence LIF production by cells stimulated by antigen or the polyclonal T cell activator, phytohemagglutinin (PHA). LTB4, at concentrations 10−7 to 10−6 M, showed significant inhibition of antigen-induced LIF production but was without effect when cells were stimulated by PHA. The cell levels of cyclic adenosine monophosphate (cAMP) were unaffected by 2.5 × 10−7 M LTB4 in the absence or presence of theophylline. These results indicate that LTB4 acts on the early effector stage of the immune response without affecting the cellular cAMp content.

Notes: Background:  Preliminary evidence suggests that inadequately controlled allergic rhinitis in asthmatic patients can contribute towards increased asthma exacerbations and poorer symptom control, which may increase medical resource use. The objective of this study was therefore to assess the effect of concomitant allergic rhinitis on asthma-related hospital resource utilization among children below 15 years of age with asthma in Norway.Methods:  A population-based retrospective cohort study of children (aged 0–14 years) with asthma was conducted using data from a patient-specific public national database of hospital admissions during a 2-year period, 1998–1999. Multivariate linear regression, adjusting for risk factors including age, gender, year of admission, urban/rural residence and severity of asthma episode, estimated the association between allergic rhinitis and total hospital days. A multivariate Cox proportional-hazards model estimated relative hazard of readmission according to concomitant allergic rhinitis status.Results:  Among 2961 asthmatic children under 15 years of age with at least one asthma-related hospital admission over a 2-year period, 795 (26.8%) had a recorded history of allergic rhinitis. Asthmatic children with allergic rhinitis had a 1.72-times greater hazard of asthma-related readmissions than asthmatic children without allergic rhinitis. Multivariate analysis revealed that history of concomitant allergic rhinitis was a significant predictor of increased number of hospital days per year (least-squares mean difference 0.23 days, P 〈 0.05).Conclusions:  Concomitant allergic rhinitis in asthmatic children was associated with increased likelihood of asthma-related hospital readmissions and greater total hospital days.

Notes: There is an increasing awareness of the importance of reliable aerosol delivery, with emphasis on the dose delivered to the lungs, optimal clinical control, cost-effectiveness, and safety in children. Dose prescription should relate to the expected lung dose rather than the factory-dispensed dose, as at present. The device determines the lung dose. Clearly, therefore, the device should be considered an integral part of the prescription. Drug approval processes should clearly specify the device, and discourage the use of other devices. This would rationalize the choice of devices. Important new insights into factors essential for drug delivery to the airways have been acquired in recent years. Nasal inhalation increases systemic bioavailability, reduces lung dose, and adds to its variability; hence, face masks to prevent nasal breathing have been developed. Similarly, dead space in the inspiratory line causes a proportional reduction in lung dose; hence, attention should be paid to reducing such dead space. Plastics in spacers cause a rapid loss of drug due to electrostatic attraction of the aerosol. The residence time of the aerosol, i. e., the time available for inhalation, is increased in nonelectrostatic spacers, allowing less compliant children enough time to obtain a full dose. Eliminating the electrostatic charge can change the lung dose by several times; hence, nonelectrostatic materials should be used in future spacer devices. Compliance is the biggest problem in drug delivery to children. The inhaler design process should be reversed, adapting technology to the child. Interactive microchip technology should provide intelligent devices that react to correct handling and breathing maneuvers. An intelligent nebulizer has been developed that adapts nebulization to the child's breathing pattern, nebulizing only during inhalation and avoiding loss of aerosol during exhalation. An automatic device (AirPacR) has been developed that transforms a dry-powder inhaler, TurbuhalerR, into a spacer. In addition to the general advantages of spacer treatment, this device offers the advantage of a drug aerosol delivered without use of propellents or additives. The mechanical actuation ensures highly repeatable drug delivery. Finally, a nonelectrostatic, tower-shaped spacer provides a stable aerosol, which remains airborne for a prolonged period. The spacer is equipped with a face mask that prevents nasal breathing. Such features should improve our ability to treat young children with inhaled drug aerosols.

Notes: An improved skin window chamber technique has been developed and used for a quantitative study of the chemotactic effect of leukotriene B4 (LTB4). LTB4 (0.5 μM) was exposed to a skin window on the forearm of eight healthy volunteers, while phosphate buffered saline served as control in a skin window on the other forearm. Skin window exudates and samples of blood draining the skin window areas were collected after 1, 2, 4, 8, and 24 h. The samples were quantitated for the different types of leukocytes as well as the intra- and extracellular concentration of the eosinophilic cationic protein and lactoferrin as markers of eosinophil and neutrophil granulocytes. A significantly increased migration of neutrophil granulocytes into the skin window chamber containing LTB4 was found from the 2nd to the 8th hour after the initial LTB4 exposure. The eosinophils reached a significant peak at the 4th hour. The rise in the actual number of eosinophil cells did not reach significance, whereas measurements of the eosinophilic cationic protein in the cellular fraction of the exudate exhibited a significant increase as a reflection of the number of eosinophils. This highlights the potential clinical value of eosinophilic cationic protein measurements to reveal eosinophilic instead of the traditional eosinophil counts. Extracellular eosinophilic cationic protein and lactoferrin did not change significantly in the LTB4-exposed skin window, implying that LTB4 does not activate the eosinophils and neutrophils to exocytosis of their enzymes. The present in vivo results support the concept of LTR4 being a potent chemoattractant to neutrophil and less so to eosinophil granulocytes in humans, a chemoattractant that recruits the leukocytes but does not seem to activate them.

Notes: Asthma represents the most common chronic disease in preschool children. Hospital admission for wheezy disorders is the most common paediatric chronic disease causing hospital admission and more common in young children than later in life.

Notes: The standard treatment of allergic rhinitis and asthma consists of topical corticosteroids administered intranasally and inhaled through the mouth. Although this therapy is highly effective, and side-effects are few and mild, it may be possible further to improve the therapeutic index and patient compliance with the treatment. In the present study, we evaluated a nasal inhalation system used for the simultaneous treatment of rhinitis and asthma. In principle, it results in an airway deposition of the corticosteroid similar to that of inhaled allergens. Twenty-four children with perennial rhinitis and asthma inhaled budesonide through the nose from a pressurized aerosol, attached to a spacer device, in a double-blind, placebo-controlled, crossover study. Compared with placebo, budesonide treatment resulted in a significant reduction of nasal symptoms (P〈0.01) and of asthma symptoms (P〈0.05), and in an increase of nasal peak inspiratory flow (P〈0.001) and of oral peak expiratory flow (P=0.01). There were no differences between budesonide and placebo in local side-effects, such as dry nose, nosebleed, and hoarseness. We conclude that nasal inhalation of a corticosteroid from a spacer offers a simple and effective treatment for both rhinitis and asthma in children, but it is an open question whether the nasal inhalation system can improve the ratio of antirhinitis/antiasthma effects to side-effects.