Bruno Mahut

Efficacy of nebulized budesonide in treatment of severe infantile asthma: A double-blind study

BACKGROUND AND OBJECTIVE Treatments with inhaled corticosteroids yielded conflicting results in infants with severe asthma. The purpose of this study was to assess the efficacy of nebulized budesonide on the control of asthma in this age group. METHODS In a double-blind, placebo-controlled study, 40 infants with severe asthma received either nebulized budesonide (1 mg) or placebo twice daily for 12 weeks, followed by a follow-up period of up to 12 weeks. A jet nebulizer driven by an air compressor was used to administer budesonide and placebo. RESULTS Fewer patients in the budesonide group had an exacerbation during the treatment period (40%) compared with the placebo group (83%, p < 0.01). The duration of oral steroid therapy was shorter in the budesonide group than in the placebo group (median number of days of exacerbation as a proportion of the total treatment time, 0% vs 14.5%; p < 0.05). The incidence of daytime (p < 0.05) and nighttime wheezing (p < 0.01) was lower in the budesonide group than in the placebo group during the treatment period. The proportion of patients without an exacerbation of asthma during the entire 24 weeks was 28% for those patients who had received budesonide and 0% for those patients who had received placebo. Asthma improved in more patients in the budesonide group (17 and 19, 89%) than in the placebo group (7 of 16, 44%; p < 0.005). These results should improve and modify the treatment of infants with severe asthma. CONCLUSION Nebulized budesonide (1 mg twice daily) is a well-tolerated and efficient treatment for severe infantile asthma.

Bronchial casts in children with cardiopathies: the role of pulmonary lymphatic abnormalities.

Expectoration of bronchial casts, a condition also called plastic bronchitis, is very rare in children. Bronchial casts may be associated with bronchopulmonary diseases associated with mucus hypersecretion, bronchopulmonary bacterial infections, congenital and acquired cardiopathies, or pulmonary lymphatic abnormalities. A classification based on anatomy and pathology has been proposed which identifies an “acellular” group associated with congenital cardiopathies and palliative surgery.

Use of polymerase chain reaction for improved diagnosis of tuberculosis in children

OBJECTIVE To study the value of a rapid diagnostic method based on the amplification by polymerase chain reaction (PCR) of a fragment of the IS6110 insertion element for the detection of Mycobacterium tuberculosis in children. DESIGN We tested 199 specimens obtained from 68 children referred for evaluation of suspected tuberculosis. RESULTS In 83.3% of children with active disease and 38.9% with tuberculous infection but no evidence of disease, at least one positive PCR result was observed. No child without tuberculosis had positive PCR results (100% specificity). The sensitivity of the PCR was increased by testing of multiple samples from the same child and use of Chelex particles (Bio-Rad Laboratories, Ivry, France) rather than guanidine isothiocyanate-silica particles for DNA extraction. Bronchoalveolar lavage samples were no more useful than gastric aspirates. CONCLUSIONS If appropriate laboratory methods are used, DNA amplification is a reliable method for the early diagnosis of tuberculosis in children and appears to be very helpful in clinical pediatric practice when the diagnosis of active tuberculosis is difficult or needs to be rapidly confirmed.

Chest computed tomography findings in bronchopulmonary dysplasia and correlation with lung function

Objective: With changes in the predominant pathogenic factors in the new form of bronchopulmonary dysplasia (BPD), a different pattern of CT findings may be expected. This study aimed to (1) describe CT findings in infants with BPD and (2) correlate the CT findings with lung function abnormalities. Study design and method: Retrospective review of 41 very low birthweight infants with BPD, who were referred for pulmonary investigations at between 10 and 20 months after birth because of persistent respiratory symptoms, and underwent CT and lung function tests. Results: None of the infants had normal CT findings. The most frequent abnormalities were hyperlucent areas (n = 36; 88%), linear opacities (n = 39; 95%), and triangular subpleural opacities (n = 26; 63%). Bronchiectasis was not seen. None of the CT abnormalities correlated with the maximum expiratory flow at functional residual capacity (VmaxFRC). In contrast, increased number of subpleural opacities and limited linear opacities were associated with low FRC and longer duration of neonatal oxygen exposure. The numbers of triangular subpleural opacities also correlated with duration of mechanical ventilation. Conclusions: Despite advances in neonatal care, many CT findings in infants with BPD are similar to those observed in the pre-surfactant era, and are still associated with duration of supplemental oxygen and mechanical ventilation. The absence of bronchial involvement in the present study was the most striking difference from previous studies.

Update on the roles of distal airways in asthma.

The present review is the summary of an expert workshop that took place in Vence (France) in 2007 on the role of distal airways in asthma. The evidence showing inflammation and remodelling in distal airways, and their possible involvement in asthma control and natural history, was reviewed. The usefulness and limitations of various techniques used for assessing distal airways were also evaluated, including pulmonary function tests and imaging. Finally, the available data studying the benefit of treatment better targeting distal airways in asthma was examined. It was concluded that both proximal and distal airways were involved in asthma and that distal airways were the major determinant of airflow obstruction. Inflammation in distal airways appeared more intense in severe and uncontrolled asthma. Distal airways were poorly attained by conventional aerosol of asthma medications owing to their granulometry, being composed of 3–5 μm particles. Both proximal and distal airways might be targeted either by delivering medications systemically or by aerosol of extra-fine particles. Extra-fine aerosols of long-acting β-agonists, inhaled corticosteroids or inhaled corticosteroid/long-acting β-agonist combinations have been shown in short-term studies to be not inferior to non-extra-fine aerosols of comparators. However, available studies have not yet demonstrated that extra-fine inhaled medications offer increased benefit compared with usual aerosols in asthmatic patients.

Multicentre trial evaluating alveolar NO fraction as a marker of asthma control and severity.

To cite this article: Mahut B, Trinquart L, Le Bourgeois M, Becquemin M‐H, Beydon N, Aubourg F, Jala M, Bidaud‐Chevalier B, Dinh‐Xuan A‐T, Randrianarivelo O, Denjean A, de Blic J, Delclaux C. Multicentre trial evaluating alveolar NO fraction as a marker of asthma control and severity. Allergy 2010; 65: 636–644.

Measurement of Dynamic Hyperinflation After a 6-Minute Walk Test in Patients With COPD

BACKGROUND Dynamic hyperinflation (DH) develops in patients with COPD during incremental exercise with a cycle ergometer. The aims of this study were to determine whether DH can be evidenced after walking with a handheld spirometer and to determine its functional consequences. METHODS Fifty patients with COPD (39 men; median age, 60 years [interquartile range (IQR), 54 to 69 years]; FEV(1), 45% predicted [IQR, 31 to 67% predicted]) underwent pulmonary function tests and a 6-min walk test (6MWT). Inspiratory capacity (IC) was measured with the patient in the standing position at rest and immediately after the 6MWT with a portable spirometer. Dyspnea was evaluated directly (change in Borg score during 6MWT) and indirectly (Medical Research Council scale). The first 20 patients performed an incremental exercise test with cycle ergometer that allowed for the measurement of IC at peak exercise and repeatedly during the first 3 min of recovery. RESULTS The median change in IC during the 6MWT was -210 mL (IQR, 55 to -440; n = 50), whereas the median change in IC during the exercise test was -295 mL (IQR, -145 to -515; n = 20). Both the IC and IC changes after 6MWT correlated to values after the exercise test. DH decreased rapidly after the end of the exercise test but was nonsignificantly different from the baseline value after 75 s of recovery. The percentage of decrease in IC during the 6MWT correlated with dyspnea (change in Borg score during 6MWT: r(2) = 0.21; p = 0.0006). CONCLUSIONS DH can be measured during a 6MWT with a handheld spirometer to allow for its evaluation in daily practice and its contribution to dyspnea while walking.

Airway Remodeling in Preschool Children with Severe Recurrent Wheeze.

RATIONALE Airway wall structure in preschoolers with severe recurrent wheeze is poorly described. OBJECTIVES To describe airway wall structure and inflammation in preschoolers with severe recurrent wheeze. METHODS Flexible bronchoscopy was performed in two groups of preschoolers with severe recurrent wheeze: group 1, less than or equal to 36 months (n = 20); group 2, 36-59 months (n = 29). We assessed airway inflammation, reticular basement membrane (RBM) thickness, airway smooth muscle (ASM), mucus gland area, vascularity, and epithelial integrity. Comparisons were then made with biopsies from 21 previously described schoolchildren with severe asthma (group 3, 5-11.2 yr). MEASUREMENTS AND MAIN RESULTS RBM thickness was lower in group 1 than in group 2 (3.3 vs. 3.9 μm; P = 0.02), was correlated with age (P < 0.01; ρ = 0.62), and was higher in schoolchildren than in preschoolers (6.8 vs. 3.8 μm; P < 0.01). ASM area was lower in preschoolers than in schoolchildren (9.8% vs. 16.5%; P < 0.01). Vascularity was higher in group 1 than in group 2 (P = 0.02) and group 3 (P < 0.05). Mucus gland area was higher in preschoolers than in schoolchildren (16.4% vs. 4.6%; P < 0.01). Inflammatory cell counts in biopsies were not correlated with airway wall structure. ASM area was higher in preschoolers with atopy than without atopy (13.1% vs. 7.7%; P = 0.01). Airway morphometrics and inflammation were similar in viral and multiple-trigger wheezers. CONCLUSIONS In preschoolers with severe recurrent wheeze, markers of remodeling and inflammation are unrelated, and atopy is associated with ASM. In the absence of control subjects, we cannot determine whether differences observed in RBM thickness and vascularity result from disease or normal age-related development.

Nitric oxide evaluation in upper and lower respiratory tracts in nasal polyposis

Background A decrease in nasal nitric oxide (NO) and an increase in exhaled NO have been demonstrated in patients with nasal polyposis (NP).

Exhaled nitric oxide in cystic fibrosis: relationships with airway and lung vascular impairments

A reduction of exhaled nitric oxide (NO) fraction and endothelial-mediated dysfunction have been reported in cystic fibrosis (CF). The aims of the present study were to search for relationships between flow-independent NO exchange parameters (bronchial NO flux (J′aw,NO) and alveolar NO concentration (CA,NO)) and lung function tests characterising airflow limitation and pulmonary vascular bed (capillary blood volume and physiological dead space/tidal volume (VD/VT) ratio on exercise). In total, 34 patients (16 children, 18 adults) with CF, without resting pulmonary hypertension, underwent spirometry, exhaled NO measurement (multiple constant flow analytical method), gas transfer assessment (carbon monoxide and NO, allowing the calculation of capillary volume and membrane conductance) and a graded exercise test with oxygen uptake (V′O2), carbon dioxide production (V′CO2) and arterial blood gas evaluations. Both J′aw,NO and CA,NO correlated positively with airflow limitation. CA,NO correlated positively with capillary/alveolar volume. During exercise, criteria of mild pulmonary vascular disease were evidenced in some patients that participated in exercise limitation (negative correlation between physiological VD/VT and peak V′O2). CA,NO at rest correlated positively with these parameters of wasted ventilation during exercise (physiological VD/VT, minute ventilation (V′E)/V′CO2 at ventilatory threshold and V′E/V′CO2 slope). Flow-independent exhaled NO parameters are linked to airway and early vascular diseases in patients with CF.