Clinical evaluation and treatment of acute asthma exacerbations in children.

This update on treatment of asthma exacerbations in children is the result of an Italian Pediatric Society Task-force, made up of a panel of experts working in 2007-2008. The aim is to give clear indications on the use of the drugs most employed in children, grading the quality of evidence and the strength of recommendations. Suggestions on their limits due to unlicensed and off-label use are reported. The level of evidence and the strength of recommendations for different therapeutic approaches demonstrate that frequently the use of drugs in children is extrapolated from the experience in adults and that more studies are required to endorse the correct use of different drugs in asthmatic children.

Optimization of emergency department management of infants with bronchiolitis.

Bronchiolitis is the most common lower respiratory tract infection in infants < 2 years of age; in the last decades both incidence and hospitalization rate had increased, thus increasing sanitary burden. From November 2006 to March 2007, an experimental protocol was followed in the Emergency Department at G. Gaslini Children's Hospital, Genoa, Italy, which attempted to optimise the management of patients with bronchiolitis and to reduce the overall hospitalization rate therefore admitting only those patients with severe illness. All clinical evaluations of the patients were obtained administering a score (Bronchiolitis Clinical Score - BCS), to quantify both initial severity of illness and response to treatment. All patient were at first treated with inhaled epinephrine, supplemented with or substituted by other drugs, if needed, according to clinical evolution. Moreover, strict admission and discharge criteria were defined, taking into consideration the BCS, response to treatment and the presence of risk factors for severe disease, attempting to increase the role of the Short Stay Unit (SSU). The outcome evaluated were the percentage of patients discharged, admitted and managed through the SSU respectively, the length of stay and the readmission rate after discharge; data collected were then compared to that regarding patients with bronchiolitis presented at the ED from November 2005 to March 2006. Our data showed an increasing of both discharged patients (37.5% vs 25.22%) and patients managed through the SSU (25.83% vs 19.57%) and a related decrease of hospitalization (36.67% vs 55.22%); no significative difference was observed regarding the readmission rate between the two populations. We also observed a statistically significant reduction of the length of stay in the study population (2.07 +/- 2.56 vs 2.84 +/- 3.25, p = 0.005). In conclusion, the protocol proposed showed to be useful in optimizing the ED management of the patient with bronchiolitis, being able to safely reduce both admission rate and lenght of stay.

Antipyretic and anti-inflammatory efficacy of nimesulide vs paracetamol in the symptomatic treatment of acute respiratory infections in children.

To evaluate the clinical efficacy of nimesulide vs paracetamol in the treatment of acute inflammatory disorders of the airways, 40 paediatric patients (aged 3 to 12 years) with acute viral infections of the lower respiratory tract not requiring systemic antibiotic therapy in the first 3 days of observation were studied. Patients were randomly divided into 2 homogeneous groups receiving either oral nimesulide 1.5 mg/kg/day 3 times daily or paracetamol 120 to 288mg (5 to 12ml) 3 times daily for 3 to 7 days. Standard laboratory tests and chest x-rays were obtained at the beginning and end of treatment, and body temperature, blood arterial pressure and heart rate were recorded regularly. The anti-inflammatory effects of the 2 drugs (based on normalisation of erythrocyte sedimentation rate, C-reactive protein values, and white blood cell counts) were evaluated and the overall duration of the disease was assessed. The results showed that nimesulide was more effective than paracetamol in normalising body temperature (p < 0.05) and in reducing the inflammatory indices (p < 0.05), and that patients in the nimesulide group required a shorter treatment period than patients in the paracetamol group. No abnormal changes in arterial blood pressure or blood and urine analyses were seen in either group, and the reduction in heart rate was similar in both groups.

Bronchial and bronchoalveolar lavage after allergen challenge in atopic patients.

Twenty patients with allergic rhinitis and/or asthma sensitised to Dermatophagoides pteronyssinus were studied. On two consecutive days they underwent methacholine challenge and allergen bronchial challenge. 72 h after allergen challenge, fibreoptic bronchoscopy with bronchial (BL) and bronchoalveolar (BAL) lavage was performed. Specific IgE antibodies were measured both in serum and in BL from 14 patients. Both BAL and BL cell differentials were similar in patients with isolated early response to allergen and in patients with dual response. Patients with dual response to allergen showed higher levels of antigen specific IgE antibodies in BL than patients with isolated early response, while IgE levels in serum were similar in the two groups.

Late-phase asthmatic reaction to inhaled allergen is associated with early recruitment of eosinophils in the airways.

To determine whether a link exists between the recruitment of inflammatory cells in the airways and the development of the late-phase asthmatic reaction, we studied with bronchoalveolar lavage 54 asthmatic patients either at baseline (10 patients) or 4 h (11 patients), 24 h (13 patients), and 72 h (20 patients) after allergen inhalation challenge. Among the patients studied 4 h after allergen challenge, five were known to have a late-phase asthmatic response and showed a significant increase in the number and percentage of eosinophils in bronchoalveolar lavage compared with either patients without late-phase response (p less than 0.05) or unchallenged patients (p less than 0.01). Both the number and the percentage of eosinophils in bronchoalveolar lavage were also increased (p less than 0.05) in patients without a late-phase asthmatic reaction studied 24 h but not in those studied 4 h after allergen challenge. The numbers and the percentages of macrophages, neutrophils, or lymphocytes did not differ significantly among the different groups of patients. Of the patients studied 4 and 24 h after allergen challenge, only those with a late-phase asthmatic response showed an increased airway responsiveness to methacholine 1 h before bronchoalveolar lavage. We conclude that the development of the late-phase asthmatic response to allergen inhalation challenge and the allergen-induced increase in airway responsiveness are associated with an early recruitment of eosinophils in the airways.

Local immunotherapy with Dermatophagoides extract in asthma.

Local immunotherapy (LIT) with Dermatophagoides extract or placebo were administered to two groups of 11 patients with allergic asthma in a double-blind fashion. All patients received cromolyn sodium (20 mg four times a day) during treatments. Bronchial provocation tests with allergen and methacholine were performed before, 1 week, and 4 weeks after the end of treatments. Symptom score, drug consumption, and peak expiratory flow were monitored daily from 2 weeks before to 4 weeks after treatments. Compared to baseline, early bronchial sensitivity to allergen was significantly reduced both 1 week (p less than 0.0005) and 4 weeks (p less than 0.01) after LIT but not after placebo administration. Late bronchial reaction to allergen occurred similarly after placebo administration and LIT. However, in the group with LIT, the severity of late reaction was unchanged after treatment in spite of the significantly larger doses of allergen administered to provoke the early asthmatic reaction. Neither symptom score, nor drug consumption, nor peak expiratory flow were significantly different in the two groups before and during the treatment period even though both symptom score and drug consumption tended to be reduced after LIT. We conclude that LIT may be an effective and safe alternative to traditional immunotherapy.

Bronchial responsiveness is not increased by bronchoalveolar and bronchial lavage performed after allergen challenge.

Nonspecific bronchial responsiveness was studied in 23 allergic patients with a history of rhinitis and/or bronchial asthma who underwent fiberoptic bronchoscopy with bronchoalveolar and bronchial lavage (BAL-BL) 4h (Group A) or 24 h (Group B) after an allergen inhalation challenge. In all patients, the dose of methacholine causing an FEV1 fall of 15% (PD15) was determined at baseline, 24 h before allergen challenge. Methacholine bronchial challenge was repeated 1 h before BAL-BL in patients of both groups and again 12 to 14 h after BAL-BL in Group A and 24 h after BAL-BL in Group B. In patients of Group A, the values of methacholine PD15 after BAL-BL were not significantly different from those determined before BAL-BL. This was also the case in patients in whom bronchial responsiveness was increased after allergen challenge. In patients of Group B, methacholine PD15 was significantly decreased after allergen challenge, and this decrease was correlated with the occurrence and the severity of the late asthmatic reaction. Even in patients who showed dual asthmatic reactions and an increased responsiveness after allergen challenge, methacholine PD15 was not further decreased after BAL-BL. These data support the safety of a procedure combining bronchial allergen challenge with BAL-BL, which can be used for studies on the pathophysiology of bronchial asthma.

Allergen-induced increase in airway responsiveness and inflammation in mild asthma.

The relationship between airway responsiveness to methacholine and inflammatory cells in bronchoalveolar lavage (BAL) was determined in patients with history of rhinitis and/or mild bronchial asthma either at baseline (10 patients) or 3-4 h after allergen inhalation challenge (11 patients). At baseline, airway responsiveness did not correlate with any BAL cell population. When data obtained after allergen challenge were included in the analysis, 44% of the variability of airway responsiveness was explained by a multiple regression model with BAL eosinophils as a directly correlated (P = 0.002) independent variable and with BAL macrophages as an inversely correlated (P = 0.045) independent variable. Changes in airway responsiveness after allergen challenge were predicted (82% of variance explained) by a model with BAL eosinophils and BAL lymphocytes as directly correlated (P = 0.0002 and P = 0.03, respectively) independent variables. We conclude that, in stable asymptomatic asthma, baseline airway responsiveness does not correlate with the presence in the airways of inflammatory and immunoeffector cells that can be recovered by BAL. Nevertheless the allergen-induced increase in airway responsiveness is associated with an influx of eosinophils and lymphocytes in the bronchial lumen.

Effect of seasonal exposure to pollen on specific bronchial sensitivity in allergic patients.

Bronchial provocation tests with aerosol of birch extract were performed before and after pollen season in 11 sensitized subjects. Changes of metacholine bronchial responsiveness and serum-specific IgE level were also assessed. In five patients who did not take steroids to control their symptoms, both early and late asthmatic responses to inhaled allergen were enhanced after season, whereas IgE serum level, but not methacholine sensitivity, was significantly increased. In six patients who needed steroids, neither responses to allergen nor IgE serum level and methacholine sensitivity were significantly changed after season. For the whole group, the increase in immediate bronchial sensitivity to allergen was positively correlated with the increase in specific IgE antibodies. We conclude that seasonal exposure to pollen has, in sensitized patients, a priming effect on bronchial mucosa that may be blunted by steroid treatment. The increased production of specific IgE antibodies appears to be an important mechanism for this priming effect.

Late asthmatic reaction to perennial and seasonal allergens.

Twelve patients with asthma sensitized to Dermatophagoides pteronyssinus and Parietaria judaica were studied. Patients were challenged before (winter), during (summer), and after (autumn) Parietaria-pollen season. Early asthmatic reaction was positive for both allergens, and the provocative dose causing a 15% decrease of FEV1 was similar in all seasons. The provocative dose of methacholine causing a 15% decrease of FEV1 and specific IgEs for both allergens were also not significantly different throughout the time of study. Late asthmatic reaction (LAR) to Dermatophagoides occurred in eight of 12 patients in winter, in six of nine in summer, and in five of six patients in autumn. The severity of LAR, expressed as the maximum fall of FEV1 3 to 8 hours after challenge, was not significantly different between seasons. LAR to Parietaria occurred in only one of 12 patients in winter, in six of 11 in summer, and in one of six patients in autumn. In summer, LAR to Parietaria was significantly more severe than in winter. In both winter and autumn, but not in summer, LAR to Dermatophagoides was significantly more severe than to Parietaria. We conclude that LAR is allergen specific, and natural exposure has a priming effect on LAR.