The butterbur extract petasin has no effect on skin test reactivity induced by different stimuli: a randomized, double-blind crossover study using histamine, codeine, methacholine, and aeroallergen solutions

BACKGROUND: Petasin (Ze 339) was recently introduced on the market as a potent herbal antiallergic drug for treatment of respiratory allergies such as hay fever. Few clinical studies have been performed so far addressing the clinical effectiveness of Ze 339. OBJECTIVE: To evaluate the antiallergic properties of Ze 339 using skin prick tests with different stimuli, such as codeine, histamine, methacholine, and a relevant inhalant allergen. METHODS: A randomized, double-blind, placebo-controlled study was performed in which Ze 339 was compared to acrivastine, a short-acting antihistamine, in 8 patients with respiratory allergy and in 10 nonatopic, healthy volunteers. Antiallergic activity of Ze 339 was determined by analyzing inhibitory potency in skin prick tests with codeine, histamine, methacholine, and an inhalant allergen. Wheal-and-flare reactions were assessed 90 minutes after a double dose of Ze 339, acrivastine, or placebo. An interval of at least 3 days was left between the skin tests. RESULTS: Acrivastine was identified as the only substance that significantly inhibited skin test reactivity to all solutions analyzed in all study subjects. In contrast, no significant inhibition could be demonstrated for Ze 339 with any test solution. Moreover, the results of Ze 339 did not differ significantly from placebo. CONCLUSIONS: In this study we found no antiallergic, particularly antihistaminic, effect of Ze 339 in skin tests using a variety of stimuli often used to evaluate immediate skin test reactivity. The mechanism by which Ze 339 is effective in the treatment of seasonal allergic rhinitis still needs to be elucidated.

Methacholine responsiveness in mice from 2 to 8 wk of age

Many chronic human lung diseases have their origin in early childhood, yet most murine models used to study them utilize adult mice. An important component of the asthma phenotype is exaggerated airway responses, frequently modelled by methacholine (MCh) challenge. The present study was undertaken to characterize MCh responses in mice from 2 to 8 wk of age measuring absolute lung volume and volume-corrected respiratory mechanics as outcome variables. Female BALB/c mice aged 2, 3, 4, 6, and 8 wk were studied during cumulative intravenous MCh challenge. Following each MCh dose, absolute lung volume was measured plethysmographically at functional residual volume and during a slow inflation to 20-hPa transrespiratory pressure. Respiratory system impedance was measured continuously during the inflation maneuver and partitioned into airway and constant-phase parenchymal components by model fitting. Volume-corrected (specific) estimates of respiratory mechanics were calculated. Intravenous MCh challenge induced a predominantly airway response with no evidence of airway closure in any age group. No changes in functional residual volume were seen in mice of any age during the MCh challenge. The specific airway resistance MCh dose response curves did not show significant differences between the age groups. The results from the present study do not show systematic differences in MCh responsiveness in mice from 2 to 8 wk of age.

Properdin in childhood and its association with wheezing and atopy

Properdin, a serum glycoprotein, is an important component of innate immunity, the only known positive regulator of complement, acting as an initiation point for alternative pathway activation. As an X-linked protein, we hypothesized that properdin may play a modulatory role in the pathogenesis of viral wheeze in children, which tends to be more common and more severe in boys. We aimed to determine properdin levels in a community-based paediatric sample, and to assess whether levels of properdin were associated with childhood wheeze phenotypes and atopy. We studied 137 school-children aged 8-12 yrs, a nested sample from a cohort study. Properdin was measured by a commercial enzyme-linked immunoabsorbant assay. We assessed wheeze by questionnaire, validated it by a nurse-led interview and performed skin prick tests and a methacholine challenge in all children. Forty children (29%) reported current wheeze. Serum properdin levels ranged between 18 and 40 microg/ml. Properdin was not associated with age, gender, atopy, bronchial responsiveness, current wheeze (neither the viral wheeze nor multiple-trigger wheeze phenotype) or severity of wheeze, but was slightly lower in south Asian (median 21.8 microg/ml) compared with white children (23.3 microg/ml; p = 0.006). Our data make it unlikely that properdin deficiency is common in healthy children or that levels of properdin are a major risk factor for wheeze or atopy.

Relationship of horse owner assessed respiratory signs index to characteristics of recurrent airway obstruction in two Warmblood families

REASONS FOR PERFORMING STUDY: The horse owner assessed respiratory signs index (HOARSI-1-4, healthy, mildly, moderately and severely affected, respectively) is based on owner-reported clinical history and has been used for the investigation of recurrent airway obstruction (RAO) genetics utilising large sample sizes. Reliable phenotype identification is of paramount importance in genetic studies. Owner reports of respiratory signs have shown good repeatability, but the agreement of HOARSI with an in-depth examination of the lower respiratory tract has not been investigated. OBJECTIVES: To determine the correlation of HOARSI grades 3/4 with the characteristics of RAO and of HOARSI-2 with the characteristics of inflammatory airway disease. Further, to test whether there are phenotypic differences in the manifestation of lung disease between families. METHODS: Seventy-one direct offspring of 2 RAO-affected Warmblood stallions (33 from the first family, 38 from the second) were graded as HOARSI-1-4 and underwent a clinical examination of the respiratory system, arterial blood gas analysis, endoscopic mucus scoring, cytology of tracheobronchial secretion (TBS) and bronchoalveolar lavage fluid (BALF), and clinical assessment of airway reactivity to methacholine chloride. RESULTS: HOARSI-3/4 animals in clinical exacerbation showed signs consistent with RAO: coughing, nasal discharge, abnormal lung sounds and breathing pattern as well as increased numbers of neutrophils in TBS and BALF, excessive mucus accumulation and airway hyper-responsiveness to methacholine. HOARSI-3/4 horses in remission only had increased amounts of tracheal mucus and TBS neutrophil percentages. Clinical phenotypes were not significantly different between the 2 families. CONCLUSIONS AND CLINICAL RELEVANCE: HOARSI reliably identifies RAO-affected horses in our population.

Mutation analysis of the muscarinic cholinergic receptor genes in isolated growth hormone deficiency type IB

BACKGROUND: Isolated GH deficiency (IGHD) is familial in 5-30% of patients. The most frequent form (IGHD-IB) has autosomal recessive inheritance, and it is known that it can be caused by mutations in the GHRH receptor (GHRHR) gene or in the GH gene. However, most forms of IGHD-IB have an unknown genetic cause. In normal subjects, muscarinic cholinergic stimulation causes an increase in pituitary GH release, whereas its blockade has the opposite effect, suggesting that a muscarinic acetylcholine receptor (mAchR) is involved in stimulating GH secretion. Five types of mAchR (M(1)-M(5)) exist. A transgenic mouse in which the function of the M(3) receptor was selectively ablated in the central nervous system has isolated GH deficiency similar to animals with defective GHRH or GHRHR gene. OBJECTIVE: We hypothesized that mAchR mutations may cause a subset of familial IGHD. PATIENTS/METHODS: After confirming the expression of M(1)-M(5) receptor mRNA in human hypothalamus, we analyzed the index cases of 39 families with IGHD-IB for mutations in the genes encoding for the five receptors. Coding sequences for each of the five mAchRs were subjected to direct sequencing. RESULTS: In one family, an affected member was homozygous for a M(3) change in codon 65 that replaces valine with isoleucine (V65I). The V65I receptor was expressed in CHO cells where it had normal ability to transmit methacholine signaling. CONCLUSION: mAchR mutations are absent or rare (less than 2.6%) in familial IGHD type IB.