Background Obstructive sleep apnea syndrome (OSA) is associated with systemic and upper airway inflammation. Pharyngeal inflammation has a potential role in upper airway collapse, whereas systemic ...inflammation relates to cardiovascular morbidity. However, the presence of an inflammatory involvement of lower airway has been poorly investigated. Objective The aim of the study was to demonstrate an inflammatory process at the bronchial level in patients with OSA and to analyze effects of continuous positive airway pressure (CPAP) application and humidification on bronchial mucosa. Methods The study was conducted by using sequential induced sputum for cell analysis and IL-8 production, nitric oxide exhalation measurement, and methacholine challenge before and after CPAP. Results Bronchial neutrophilia and a high IL-8 concentration were observed in untreated OSA compared with controls (75% ± 20% vs 43% ± 12%, P < .05; and 25.02 ± 9.43 ng/mL vs 8.6 ± 3.7 ng/mL, P < .001, respectively). IL-8 in sputum supernatant was correlated to apnea hypopnea index ( P < .01; r = 0.81). After 1 month of CPAP, this inflammatory pattern remained unchanged, and an increase in airway hyperresponsiveness (AHR) was observed ( P < .001). Conclusion Obstructive sleep apnea syndrome is associated with bronchial inflammation. Our data demonstrate CPAP effect on the development of AHR, possibly facilitated by the pre-existing inflammation. Both issues should be evaluated during long-term CPAP use. Clinical implications Results showing a spontaneous bronchial inflammation in OSA and the development of a CPAP-related AHR require a long-term follow-up to evaluate consequences on chronic bronchial obstruction.
Background Integrin β3 ( ITGB3 ) and Toll-like receptor 2 ( TLR2 ) are candidate genes for asthma and sensitization to mold allergens. Integrin β3 forms a complex with TLR2, and this biological ...interaction is required for the response of monocytes to TLR2 agonists such as fungal glucan. Objective To study whether genetic interaction between single nucleotide polymorphisms (SNPs) in genes encoding the TLR2-ITGB3 complex enhances susceptibility to mold sensitization. Methods Association analysis was conducted in 1243 adults (524 with asthma) who participated in the follow-up of the Epidemiological Study on the Genetics and Environment of Asthma. Allergic sensitization to mold allergens was determined by skin prick testing. Association of mold sensitization with 14 ITGB3 SNPs was tested under an additive genetic model. Interaction between ITGB3 SNPs and TLR2 /+596, which was previously shown to be associated with asthma, was studied. Results A positive skin prick test to mold was found in 115 subjects with asthma (22.0%) and in 61 subjects without asthma (8.5%). The ITGB3 rs2056131 A allele was associated with mold sensitization in subjects with asthma with an odds ratio (95% CI) of 0.60 (0.43-0.83; P = .001). Ten other ITGB3 SNPs were significantly associated with mold sensitization in TLR2 /+596TT subjects with asthma ( P = .03-.002), whereas much weaker associations were found in carriers of the TLR2 /+596 C allele ( P = .60-.04). Interaction between TLR2 /+596 and these ITGB3 SNPs was statistically significant ( P interaction = .05-.001). Conclusion TLR2/+596 genotype may influence the association between ITGB3 SNPs and mold sensitization in adults with asthma.
No data are available regarding the utility of fractional exhaled nitric oxide (FeNO) level in guiding therapy in smoking asthmatic patients. Identification of the effect of smoking in a large sample ...is needed.
To study the association between smoking and FeNO level according to current asthma and atopy status in adults from the French EGEA (Epidemiological study on the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy).
Levels of FeNO were measured at 50 mL/s in 654 adults (268 asthmatic participants). Active smoking and environmental tobacco smoke (ETS) exposure at home, at work, and during leisure activities were recorded. Participants were categorized as having no exposure to ETS, mild exposure (ETS <2 h/d), and noticeable exposure (ETS > or = 2 h/d). Multivariate analyses were performed, with adjustment for age, sex, height, and center.
Mean adjusted FeNO values increased with asthma (15.1 vs 19.5 ppb), atopy (14.2 vs 18.9 ppb), and eosinophilia (15.8 vs 24.8 ppb) (P < .001 for all). Mean FeNO levels decreased with smoking (18.4, 17.5, and 14.5 ppb in nonsmokers, ex-smokers, and current smokers, respectively; P for trend = .001). The association with smoking was observed in nonasthmatic and asthmatic participants, especially in atopic asthmatic participants. Multivariate analyses showed that ETS exposure of at least 2 h/d and active smoking were negatively and significantly associated with FeNO levels independent of age, sex, height, and center in nonasthmatic participants (mean SE, -0.13 0.06, P = .03 and -0.10 0.03, P < .001) and in asthmatic participants (mean SE, -0.18 0.07, P = .01 and -0.14 0.04, P = .02).
Active and passive smoking decreased FeNO levels in adults. Careful consideration of asthma, atopy, and active and passive smoking are needed to interpret FeNO values.
Objective To evaluate parental stress after a false-positive result at the time of the cystic fibrosis (CF) newborn screening (NBS), attributable to heterozygotism or persistent hypertrypsinemia. ...Study design A prospective study was conducted in 86 French families at 3, 12, and 24 months after NBS. A psychologist conducted interviews with a questionnaire, the Perceived Stress Scale, and the Vulnerable Child Scale. Results Overall, 96.5% of parents said they had been anxious at the time of the sweat test. However, 86% felt entirely reassured 3 months after the test. The mean Perceived Stress Scale score did not differ from that observed in the French population. Mean Vulnerable Child Scale scores were high, associated with a low Parental Perception of Child Vulnerability. These results did not differ significantly at 1 and 2 years. In total, 86% to 100% of families no longer worried about CF. All parents stated that they would have the test performed again for another child. Conclusions CF NBS can lead to false-positive results, causing parental anxiety, which quickly decreases after a sweat test performed soon after the phone call.
To evaluate the additional information provided by pulse transit time (PTT), a noninvasive tool, when using during polysomnography for the diagnosis of sleep breathing disorders in a pediatric ...population
Respiratory and microarousals events were scored twice. The first scoring was performed using nasal pressure, thermistors, thoracic and abdominal movements, and oxygen saturation. The second scoring, blinded to the first scoring, was performed using PTT in combination with all the other signals. Microarousals were scored once visually on the EEG trace (cortical arousals CAs) and once using the PTT signal (autonomic arousals AAs) blinded to EEG. For the whole group of 16 children studied (mean age, 9.5 years), there was no significant difference between the respiratory disturbance index (RDI) with or without PTT analysis (22.4 ± 13.5/h vs 20.4 ± 14.3/h; not significant mean ± SD). Among the children exhibiting a “without PTT” RDI < 30/h, 5 of 12 children (41.66%) showed a clinically significant ≥ 5/h increase in RDI when using PTT. AAs detected by PTT were significantly more frequent than CAs during rapid eye movement (REM) sleep (7.4 ± 3.9/h vs 3.2 ± 2.3/h; p < 0.001) and slow wave sleep (SWS) 6.0 ± 4.3/h vs 0.6 ± 0.5/h; p < 0.0001
The quantification of respiratory effort using PTT improves the detection of respiratory events in children. The detection of microarousals is improved particularly in REM and SWS
The identification of the factors associated with severe asthma may shed some light on its etiology and on the mechanisms of its development. We aimed to describe asthma severity using the Global ...Initiative for Asthma (GINA) classification and to investigate its determinants in a cross-sectional, population-based sample in Europe.
In the European Community Respiratory Health Survey II (1999-2002), 1,241 adults with asthma were identified. Severity was assessed using the 2002 GINA classification (intermittent, mild persistent, moderate persistent, severe persistent) and it was related to potential determinants by a multinomial logistic model, using the intermittent group as the reference category for relative risk ratios.
About 30% of asthmatic subjects were affected by moderate-to-severe asthma. Sensitization to Cladosporium was associated with a more than 5-fold greater risk of having (mild, moderate or severe) persistent asthma than intermittent asthma. Persistent asthma was positively associated with sensitization to house dust mite, nonseasonal asthma, an older age at asthma onset, and chronic cough and phlegm. Sensitization to cat increased the risk of severe asthma only. Smoking was more strongly associated with asthma severity in men, while rhinitis was more strongly associated with asthma severity in women.
One third of the asthmatic population have moderate-to-severe asthma. Sensitization to perennial indoor allergens, particularly Cladosporium, is strongly associated with asthma severity. The role of smoking and rhinitis in determining asthma severity may differ between the sexes, and it should be further investigated.
Lung damage in cystic fibrosis (CF) is strongly associated with lower airway infections. Early treatment of
is recommended. Pathogen detection requires sampling of lower airway secretions, which ...remains a challenge in nonexpectorating patients. Our hypothesis was that chest physiotherapy would improve the quality of airway secretion samples and increase the rates of pathogens detected in nonexpectorating patients. This prospective multicentre study compared three successive methods for sampling airway secretions applied through the same session: 1) an oropharyngeal swab (OP), 2) a chest physiotherapy session followed by a provoked cough to obtain sputum (CP-SP) and 3) a second oropharyngeal swab collected after chest physiotherapy (CP-OP).
,
and
growth cultures were assessed. Accuracy tests and an equivalence test were performed to compare the three successive methods of collection. 300 nonexpectorating children with CF were included.
was detected cumulatively in 56 (18.9%) children, and according to the different collection methods in 28 (9.8%), 37 (12.4%) and 44 (14.7%) children by using OP, CP-OP and CP-SP, respectively. Compared with OP, the increased detection rate was +22% for CP-OP (p=0.029) and +57% for CP-SP (p=0.003). CP-SP had the best positive predictive value (86.3%) and negative predictive value (96.0%) for
compared with the overall detection. The results of this adequately powered study show differences in the rates of pathogens detected according to the sampling method used. Chest physiotherapy enhanced detection of
in nonexpectorating children with CF.
A genome-wide search was conducted in 107 nuclear families with at least two siblings with asthma, as part of the French EGEA study. A two-stage analysis strategy was applied to the 107 families ...divided into two independent subsets of 46 and 61 families, where all regions detected in the first set of families were tested for replication in the second set. In addition, all regions reported by published genome scans in different populations were examined in the total sample. A total of 254 markers were typed in the first set of families and 70% of them in the second set. Linkage was investigated by model-free methods for asthma and four asthma-related phenotypes: bronchial responsiveness (BR), skin test response, total immunoglobulin E (IgE) levels, and eosinophil count. The two-stage analysis led to the detection of three regions: 11p13 for IgE, 12q24 for eosinophils, and 17q12-21 for asthma and skin tests. Among the regions reported by published genome screens, seven were found in the 107 French EGEA families: three being already detected by the two-stage analysis, 11p13 (p = 0.005), 12q24 (p = 0.0008), and 17q12-21 (p = 0.001), and four additional ones, 1p31 (p = 0.005) for asthma, 11q13 (p = 0.006) for IgE, 13q31 (p = 0.001) for eosinophils, and 19q13 (p = 0.02) for BR.
Background Little is known about factors associated with lung function decline in asthma. Objective To identify the determinants of FEV1 decline in adults with asthma with and without airflow ...obstruction at baseline. Methods An international cohort of 638 subjects with asthma (20-44 years old) was identified in the European Community Respiratory Health Survey (1991-1993) and followed up from 1998 to 2002. Spirometry was performed on both occasions. FEV1 decline was related to potential determinants evaluated at baseline and during the follow-up by random intercept linear regression models. The analyses were stratified by the presence of airflow obstruction (FEV1 /forced vital capacity < 0.70) at baseline. Results In the group of individuals without airflow obstruction (n = 544), a faster FEV1 decline was observed for subjects with intermediate body mass index (BMI) than for lean and obese subjects. FEV1 decline was associated with weight gain independently of baseline BMI, and this association was stronger in men (20; 95% CI, 10-30, mL/y/kg gained) than in women (6; 95% CI, 1-11, mL/y). In the group of individuals with airflow obstruction (n = 94), the absence of allergen sensitization and a low BMI at baseline were associated with a faster FEV1 decline, whereas weight gain was not associated with decline. Conclusions The detrimental effect of weight gain on FEV1 decline is particularly relevant in subjects with asthma who still do not have an established airflow obstruction. Our findings support the importance of weight management in asthma and recommend weight loss in overweight or obese individuals with asthma.
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