Time-effect of montelukast on protection against exercise-induced bronchoconstriction.

INTRODUCTION: Montelukast has been proven to assure a protective effect against exercise-induced bronchoconstriction. AIM: To verify exactly when montelukast begins protection in asthmatic children by evaluating different time intervals between dosing and challenge. METHODS: In a double blind, placebo-controlled, three day doses, crossover study, patients were randomized to receive in sequence treatment with either a placebo or montelukast and assigned to one of seven groups that were tested 1, 2, 3, 4, 5, 6 and 8 h after drug administration, respectively. For each group, the exercise challenge was always performed at the same hour on the first and third days of treatment. RESULTS: Sixty-nine asthmatic children took part in the study. On day 3, the mean FEV(1) % fall from baseline was 25.54 (95% CI = 21.63/29.46) and 14.89 (95% CI = 11.85/17.92) for the placebo and active drug (p < 0.05), respectively. On day 1, the mean fall of FEV(1) was 28.20 (95% CI = 24.46/31.94) and 19.01 (95% CI = 15.71/22.31) for the placebo and montelukast (p < 0.05), respectively. Clinical protection was achieved in 21 (30%) and 33 (48%) subjects by montelukast on the first and third days, respectively. CONCLUSIONS: Montelukast assured protection against exercise-induced bronchoconstriction from the first through the eighth hour from the first day of treatment. However, individual susceptibility to protection was evident since some individuals were not protected at any time. We conclude that in clinical use individual responses to the drug should be carefully evaluated in the follow-up management.

Immune regulatory cytokines in the milk of lactating women from farming and urban environments.

Children living on farms have fewer allergies. It is unclear whether breastfeeding in different environments contributes to preventing allergies by exposing offspring to different cytokines that can modulate immune responses. The aim of this study was to quantify and compare levels of Transforming Growth Factor-beta1 (TGF-beta1) and Interleukin-10 (IL-10) in the colostrum and mature milk of mothers living in towns at sea level (references) and mothers on farms. Milk samples were collected within 3 days postpartum (colostrum) and at the first month of the baby's life (mature milk). Sixty-nine reference mothers and 45 farm mothers participated in the study. TGF-beta1 concentrations were significantly higher both in the colostrum (p < 0.05) and in mature milk (p < 0.05) of farm mothers. In the reference mothers, a significant decrease in TGF-beta1 concentrations was observed between colostrum (650, range 0-8000 pg/ml) and mature milk (250, range 0-8000 pg/ml) (p < 0.05). In farm mothers, TGF-beta1 concentrations were 1102 pg/ml (range 0-14,500) in colostrum and remained high in mature milk (821 pg/ml, range 0-14,650). IL-10 concentrations were higher in the mature milk of farm mothers (p < 0.05). No significant differences in IL-10 were observed between colostrum and mature milk in the control group (15 pg/ml, range 0-1800, and 0 pg/ml, range 0-230) or in farm mothers (9.5 pg/ml, range 0-1775, and 14.2 pg/ml, range 0-930), respectively. Exposure to a farm environment is associated with higher concentrations of TGF-beta1 and IL-10 in breast milk when compared to exposure to an urban environment. Higher cytokine concentrations in breast milk may influence early modulation of the development of an immune response, leading to a reduced prevalence of allergy-related diseases in farm children.

Atypical bacteria in adenoids and tonsils of children requiring adenotonsillectomy.

CONCLUSIONS: The results of this study suggest that atypical bacteria may be involved not only in acute upper airway diseases but also in recurrent infections requiring adenoidectomy and/or tonsillectomy. Therefore, their identification, followed by an appropriate treatment, should be considered. OBJECTIVE: Although viruses and group A beta-haemolytic streptococci (GABHS) represent the most frequent bacterial aetiological agents of paediatric upper respiratory tract infections (URTIs), chlamydia and Mycoplasma pneumoniae have also been found in acute tonsillopharyngitis. Nevertheless their relevance in chronic or recurrent URTI has never been evaluated. This study aimed to further address the role of atypical bacteria in recurrent URTIs requiring adenoidectomy and tonsillectomy. METHODS: Samples from 55 consecutive children who underwent adenoidectomy and/or tonsillectomy for recurrent or chronic URTI were cut transversely into smaller sections of 5 mm. Each section was pooled and assayed by specific PCR for viruses and bacteria. RESULTS: Adenovirus was detected in 10 patients (18.2%), influenza A virus in one patient and influenza B virus in another. None of the other tested viruses was found. GABHS was found in 37 patients (67.3%). Moraxella catarrhalis and Haemophilus influenzae were detected in 30 patients (54.5%). M. pneumoniae was detected in 6 patients (10.9%) and C. pneumoniae was found in 10 patients (18.2%).

Effective desensitization to imiglucerase in a patient with type I Gaucher disease.

We describe a child who had anaphylactic hypersensitivity to imiglucerase therapy for Gaucher disease. Treatment was stopped and symptoms returned. After immune desensitization to imiglucerase using a rush protocol, the patient was able to resume treatment and has not had further hypersensitivity complications to date.

Comparison of human metapneumovirus genotypes from the province of Bolzano in northern Italy with strains from surrounding regions in Italy and Austria.

The epidemiology of the genetic sublineages of human metapneumovirus (hMPV) and their clinical relevance are not fully understood. We compared hMPV genotypes isolated in the province of Bolzano in Northern Italy with strains from nearby Italian and Austrian regions by sequencing of NP- and L-gene fragments. Our results suggest that similar strains cycle through adjacent geographic areas, with the respective subtypes replacing each other on a seasonal basis.

IRAK-M is involved in the pathogenesis of early-onset persistent asthma.

Asthma is a multifactorial disease influenced by genetic and environmental factors. In the past decade, several loci and >100 genes have been found to be associated with the disease in at least one population. Among these loci, region 12q13-24 has been implicated in asthma etiology in multiple populations, suggesting that it harbors one or more asthma susceptibility genes. We performed linkage and association analyses by transmission/disequilibrium test and case-control analysis in the candidate region 12q13-24, using the Sardinian founder population, in which limited heterogeneity of pathogenetic alleles for monogenic and complex disorders as well as of environmental conditions should facilitate the study of multifactorial traits. We analyzed our cohort, using a cutoff age of 13 years at asthma onset, and detected significant linkage to a portion of 12q13-24. We identified IRAK-M as the gene contributing to the linkage and showed that it is associated with early-onset persistent asthma. We defined protective and predisposing SNP haplotypes and replicated associations in an outbred Italian population. Sequence analysis in patients found mutations, including inactivating lesions, in the IRAK-M coding region. Immunohistochemistry of lung biopsies showed that IRAK-M is highly expressed in epithelial cells. We report that IRAK-M is involved in the pathogenesis of early-onset persistent asthma. IRAK-M, a negative regulator of the Toll-like receptor/IL-1R pathways, is a master regulator of NF- kappa B and inflammation. Our data suggest a mechanistic link between hyperactivation of the innate immune system and chronic airway inflammation and indicate IRAK-M as a potential target for therapeutic intervention against asthma.

Nebulizers or pressurized metered-dose inhalers in the treatment of asthma exacerbations.

The use of inhaled beta2-agonists delivered by a metered-dose inhaler (MDI) with a holding chamber (spacer) actually is considered the best treatment for childhood acute asthma. However, its use in daily practice still seems rather limited. The aim of this study was to investigate, using a questionnaire, the use of a nebulizer or MDI as the first-line method for delivering inhaled beta2-agonists in children with acute asthma. A questionnaire was developed and distributed to 22 pediatric departments and to 131 family pediatricians (FPs) in northeast Italy. We showed that in the hospitals the episodes of acute asthma usually were treated with bronchodilators administered by wet nebulization (95.45%). This was the case also for FPs (70.9%). However, 29.1% of FPs usually advised the use of an MDI/holding chamber to children with acute asthma. Despite the established efficacy of inhaled beta2-agonists administrated with an MDI compared with wet nebulization in acute asthma, this practice still is rather limited. The use of wet nebulization was more evident in hospital settings compared with community medicine. Emergency room visits may represent a missed opportunity to promote an effective method of delivering bronchodilators in childhood asthma.

Association of the interleukin-1 receptor antagonist gene with asthma.

The interleukin-1 cluster on human chromosome 2q12-2q14 harbors various promising candidate genes for asthma and other inflammatory diseases. We conducted a systematic association study with single-nucleotide polymorphisms (SNPs) located in candidate genes situated in this cluster. Single-marker, two-locus and three-locus haplotype analysis of SNPs yielded several significant results (p < 0.05-0.0021) for the human IL1RN gene encoding the IL-1 receptor antagonist protein, an antiinflammatory cytokine that plays an important role in maintaining the balance between inflammatory and antiinflammatory cytokines. These findings were replicated and confirmed in an independent Italian family sample in which significant, although weaker, association with asthma was detected. A sequencing approach to the coding region of the human IL1RN gene revealed additional DNA variants, from which a selection was also associated with the disease in German and Italian samples. Calculation of the linkage disequilibrium for the human IL1RN gene showed strong linkage disequilibrium for nearly all analyzed SNPs. Further haplotype analysis indicated that six SNPs are sufficient for tagging all haplotypes with a prevalence of more than 1%. The most frequent haplotype constructed from these SNPs was 1.4-fold overtransmitted in the German family sample.