Serge Waernessyckle

Effect of mutator P. aeruginosa on antibiotic resistance acquisition and respiratory function in cystic fibrosis.

Cystic fibrosis patients suffer from recurrent bacterial infections that result in progressive deterioration of their respiratory function. Despite intensive antibiotic treatment, Pseudomonas aeruginosa is the main cause of such infections, with clones progressively developing multiple antibiotic resistance. We determined the relationship between the presence of P. aeruginosa mutator strains and cystic fibrosis clinical characteristics.

Relationship between Bronchial Hyperresponsiveness and Impaired Lung Function after Infantile Asthma

Wheezing during infancy has been linked to early loss of pulmonary function. We prospectively investigated the relation between bronchial hyperresponsiveness (BHR) and progressive impairment of pulmonary function in a cohort of asthmatic infants followed until age 9 years. We studied 129 infants who had had at least three episodes of wheezing. Physical examinations, baseline lung function tests and methacholine challenge tests were scheduled at ages 16 months and 5, 7 and 9 years. Eighty-three children completed follow-up. Twenty-four (29%) infants had wheezing that persisted at 9 years of age. Clinical outcome at age 9 years was significantly predicted by symptoms at 5 years of age and by parental atopy. Specific airway resistance (sRaw) was altered in persistent wheezers as early as 5 years of age, and did not change thereafter. Ninety-five per cent of the children still responded to methacholine at the end of follow-up. The degree of BHR at 9 years was significantly related to current clinical status, baseline lung function, and parental atopy. BHR at 16 months and 5 years of age did not predict persistent wheezing between 5 and 9 years of age, or the final degree of BHR, but it did predict altered lung function. Wheezing that persists from infancy to 9 years of age is associated with BHR and to impaired lung function. BHR itself is predictive of impaired lung function in children, strongly pointing to early airway remodeling in infantile asthma.

Relationships between Specific Airway Resistance and Forced Expiratory Flows in Asthmatic Children

Background The earliest changes associated with airflow obstruction in asthmatic children are a proportionally greater reduction in FEF50% than in FEV1 using spirometry, and an increase in specific airway resistance (sRaw) using body plethysmography. Consequently, we hypothesized that sRaw could be better linked to FEF50% than to FEV1. The first aim was to assess the relationships between forced expiratory flows and sRaw in a large group of asthmatic children in a transversal study. We then performed a longitudinal study in order to determine whether sRaw of preschool children could predict subsequent impairment of forced expiratory flows at school age. Methodology Pulmonary function tests (sRaw and forced expiratory flows) of 2193 asthmatic children were selected for a transversal analysis, while 365 children were retrospectively selected for longitudinal assessment from preschool to school age. Principal Findings The transversal data showed that sRaw is differently related to FEF50% (−1/sRaw) and to FEV1 (near linearly). These results were further explained by a simple one-compartment lung model, which justified the shape of the observed relationships. As hypothesized, sRaw correlated more strongly to FEF50% than to FEV1 (r = −0.64 versus −0.39, respectively; p<0.001). In the longitudinal part of the study, sRaw at preschool age correlated with subsequent FEF50% (% predicted) (−0.31, 95% CI, −0.40 to −0.22), but weakly with subsequent FEV1 (% predicted) (−0.09, 95% CI, −0.20 to 0). Conclusion Specific Raw is more strongly related to FEF50% than to FEV1 and could be used in preschool children to predict subsequent mild airflow limitation.

Repeatability of lung function tests during methacholine challenge in wheezy infants

BACKGROUND The repeatability of lung function tests and methacholine inhalation tests was evaluated in recurrently wheezy infants over a one month period using the rapid thoracic compression technique. METHODS Eighty one wheezy, symptom free infants had pairs of methacholine challenge tests performed one month apart. Maximal flow at functional residual capacity (V˙maxfrc) and transcutaneous oxygen tension (Ptco 2) were measured at baseline and after methacholine inhalation. Provocative doses of methacholine causing a 15% fall in Ptco 2(PD15Ptco 2) or a 30% fall inV˙maxfrc (PD30V˙maxfrc) were determined. RESULTS Large changes in V˙maxfrcwere measured from T1 to T2 with a mean difference between measurements (T2—T1) of 7 (113) ml/s and a 95% range for a single determination forV˙maxfrc of 160 ml/s. The mean (SD) difference between pairs of PD30V˙maxfrc measurements was 0.33 (1.89) doubling doses with a 95% range for a single determination of 2.7 doubling doses. Repeatability of PD15Ptco 2 was similar. A change of 3.7 doubling doses of methacholine measured on successive occasions represents a significant change. CONCLUSIONS Baseline V˙maxfrcvalues are highly variable in wheezy, symptom free infants. Using either V˙maxfrc or Ptco 2 as the outcome measure for methacholine challenges provided similar repeatability. A change of more than 3.7 doubling doses of methacholine is required for clinical significance.

Diagnostic value of nasal provocation challenge with allergens in children.

A total of 106 children suffering from perennial rhinitis and/or asthma, and all allergic to Dermatophagoides pteronyssinus (DP), underwent nasal provocation challenge (NPC) with DP to determine the best method of diagnosis. Posterior rhinomanometry was uninterpretable in 17 patients and gave negative results in 31. Clinical scores for sneezing and rhinorrhea were more effective but did not diagnose the disorder in 11 children. However, nine of the 11 had significant increases in eosinophil count in the late phase. Clinical scores and cytology were also useful for assessing whether NPC with allergens was positive in children. The feasibility and safety of NPC with DP are high for rhinitic and stable asthmatic patients, but mild reactions may occur during the late phase.

Nitric oxide in children with persistent asthma

OBJECTIVE To assess the difference in exhaled nitric oxide levels in atopic and nonatopic asthmatic patients treated with anti-inflammatory drugs, and to compare exhaled nitric oxide measurement with lung function tests. METHODS Cross-sectional study with 45 consecutively selected patients with moderate and severe persistent asthma, aged between 6 and 17 years, and treated with anti-inflammatory drugs for at least 1 year. The patients were split into two groups: atopic ones (with positive skin tests) and nonatopic ones. The clinical and functional assessments and the measurement of exhaled nitric oxide were carried out concomitantly. RESULTS There was a male predominance (62.5%), with an age range between 6 and 13 years (mean of 10.4 years) in 85% of the patients. Neither the symptoms associated with asthma (p = 0.07), allergic rhinitis (p = 0.17), food allergy (p = 0.09), necessity of systemic corticosteroids (p = 0.10), antileukotrienes (p = 0.20) and antihistamines (p = 0.70), nor the three parameters used to assess lung function (FEV(1), FEV(1)/FVC and FEF(25-75%), p > or = 0.14) were statistically significant. The frequency of eczema (p < 0.005) and exhaled nitric oxide levels (p < 0.001) were higher among atopic patients. CONCLUSION Results suggest that clinical and functional stability of asthma among atopic patients does not necessarily reflect an efficient control over the inflammatory process and a higher probability for recurrence after discontinuation of anti-inflammatory therapy.

Ability of new lung function tests to assess methacholine-induced airway obstruction in infants

Summary We assessed the ability of innovative lung function tests to detect bronchial obstruction induced by methacholine bronchial challenge. Fifty-five recurrently wheezy infants (mean age 16 ± 5.2 months) free of respiratory symptoms underwent baseline lung function tests. Forty-two completed the methacholine challenge. Maximal flow at functional residual capacity (VmaxFRC) was obtained using the squeeze technique; compliance and resistance of the respiratory system (Crs, Rrs) was measured with the passive expiratory flow volume technique; tidal volume breathing patterns were analyzed from recordings of respiratory rate (RR), tidal volume (VT), and inspiratory time divided by total cycle of duration (Ti/Ttot). Expiratory tidal flow volume (V/VT) curves were described with multiple indices such as the ratio of expiratory time necessary to reach peak tidal expiratory flow (Fpet) to expiratory time (Tme/Te). Transcutaneous oxygen tension (PcO2) was measured as an indicator of response to methacholine challenge. Of 42 infants 41 responded to methacholine by a change ≥ 2 standard deviations from baseline values. The mean SD unit changes were 9.8 in PcO2, 3.7 for VmaxFRC, 2.8 for Crs, 2.09 for Rrs, 3.1 for RR, 1.6 for Ti/Ttot, 2.2 for Tme/Te 3.9 for PFvt. We conclude that these noninvasive lung function tests, especially VmaxFRC and Fpet, can be used to detect minor or moderate airway obstruction. Further studies are needed to determine the value of the tests in assessing bronchial disease and effects of its treatment.